Analgesic efficacy of 7 different topical NSAIDs in panretinal photocoagulation-associated pain

Analgesic efficacy of 7 different topical NSAIDs in panretinal photocoagulation-associated pain | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Analgesic efficacy of 7 different topical NSAIDs in panretinal photocoagulation-associated pain Ahmet Kürşad SAKALLIOĞLU, Tülay ENGİN, Tuğçe BEK, Hande GÜÇLÜ This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6790841/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 02 Oct, 2025 Read the published version in BMC Ophthalmology → Version 1 posted 11 You are reading this latest preprint version Abstract Background To investigate the effects of different topical non-steroidal anti-inflammatory drugs (NSAIDs) and demographic characteristics on pain perception associated with pan-retinal photocoagulation. Methods Before pan-retinal photocoagulation, patients received one of seven topical NSAIDs, while the control group received artificial tears. Following pan-retinal photocoagulation, subjective pain was assessed using the visual analog scale. The impact of demographic factors and NSAID type on visual analog scale scores was statistically analyzed. Demographic data were compared using the Mann-Whitney U test and NSAID groups with one-way ANOVA. Results The study included 270 eyes from 270 patients. No significant differences were observed among NSAID groups regarding age, gender, diabetes duration, diabetic retinopathy type, number of intravitreal injections, pan-retinal photocoagulation sessions, or photocoagulation energy. In all participants, pain perception was higher in females (P < 0.001), patients aged ≤ 60 years (P < 0.001), and those with proliferative diabetic retinopathy (P < 0.001). Bromfenac (P < 0.001), indomethacin (P < 0.001), nepafenac 0.3% (P = 0.002), and diclofenac (P = 0.029) significantly reduced pain, whereas ketorolac trometamol, nepafenac 0.1%, and flurbiprofen did not. Among the effective NSAIDs, nepafenac 0.3% and diclofenac were ineffective in males, while diclofenac showed no efficacy in patients over 60 years of age or those with proliferative diabetic retinopathy. No NSAID demonstrated a significant effect in non-proliferative diabetic retinopathy patients. Conclusions Bromfenac and indomethacin demonstrate consistent analgesic efficacy in nearly all patients with pan-retinal photocoagulation-related pain, while nepafenac 0.3% and diclofenac are effective in a majority of cases. However, heightened pan-retinal photocoagulation-related pain in females, patients aged ≤ 60 years and those with proliferative diabetic retinopathy may necessitate careful consideration in these populations. Non-steroidal anti-inflammatory drug Diabetic Retinopathy Topical analgesic Eye Drops Panretinal Photocoagulation Background Diabetes mellitus is a major global health challenge, affecting nearly 500 million individuals worldwide ( 1 ). This metabolic disorder is a significant burden on health systems due to its association with many complications ( 2 , 3 ). Diabetic retinopathy (DRP) is one of the most prevalent and severe ocular complications and approximately 4.5 million people have vision impairment or blindness due to this condition ( 2 , 4 ). DRP develops due to progressive microvascular dysfunction, leading to retinal ischemia, abnormal blood vessel growth, and macular edema ( 2 , 5 ). As DRP advances to its proliferative stage, known as proliferative diabetic retinopathy (PDR), retinal ischemia and pathological neovascularization develop on the retinal surface, substantially elevating the risk of severe vision loss ( 2 , 6 ). Panretinal photocoagulation (PRP) is a well-established treatment for reducing the risk of severe vision loss in patients with PDR ( 7 ). Unfortunately, PRP is often a painful procedure for many patients. Pain and discomfort may hinder patients from completing PRP therapy or necessitate its early termination, potentially resulting in poor adherence to laser treatment, which is essential for the effective management of PDR ( 8 ). To minimize this discomfort during PRP, many pain-reducing molecules and application methods have been investigated in previous studies. These methods include oral, intramuscular, subtenon, peribulbar, subconjunctival, topical, and even inhalation ( 9 ). However, systemic drugs have side effects, and interventional methods have many complications that may occur during the procedure ( 10 , 11 ). Considering that diabetes is a disease that affects half a billion people ( 1 ), we believe that the number of these side effects and complications will be considerable and that these side effects and complications can be avoided to some extent with topical analgesic applications. Therefore, in this study, we investigated the demographic characteristics of patients and the efficacy of topical non-steroidal anti-inflammatory drugs (NSAIDs) on PRP-related subjective pain sensation. Methods This single-center, cross-sectional, retrospective, placebo-controlled, comparative case series was conducted with 270 eyes of 270 patients who underwent PRP for non-proliferative diabetic retinopathy (NPDR) or PDR in a university teaching hospital. The right eyes of participants who underwent bilateral or right PRP application, and the left eyes of participants who underwent left PRP application were included in the study. The decision for PRP application was made within the indications determined by the Diabetic Retinopathy Study Research Group ( 12 ). The distinction between NPDR and PDR was made using fluorescein fundus angiography performed with the Canon CX-1 fundus camera (Canon INC., Tokyo, Japan). Demographic data such as age, gender, number of previous intravitreal injections (IVIs), and previous PRP applications and parameters were noted from patient files. A total of 270 eyes in 8 groups were given only one of 7 different NSAIDs in the lower conjunctival cul-de-sac of the study eye, 30 to 45 minutes before the procedure, which are: nepafenac %0.1 (Nevanac, Alcon Laboratories Ltd, Hertfordshire, UK) (Nep1 group), nepafenac 0.3% (Apfecto 0.3%, World Medicine Ophthalmics, İstanbul, Turkey) (Nep3 group), ketorolac trometamol 0.5% (Acular, Allergan Pharmaceuticals, Westport, Ireland) (Keto group), diclofenac sodium 0.1% (Inflased, Bilim, Turkey) (Diclo group), flurbiprofen 0.03% (Flubord, World Medicine Ophthalmics, İstanbul, Turkey) (Flur group), indomethacin 0.1% (Indocollyre, Bausch & Lomb–Laboratoire Chauvin, Montpellier, France) (Indo group), bromfenac 0.09% (Yellox; Bausch & Lomb Swiss AG, Zug, Switzerland) (Brom group), and the control group consisted of patients who were administered artificial eye drop instead of topical NSAIDs. All patients received one topical Proparacaine HCl 0.5% eye drop (Alcaine; Alcon Laboratories, Inc., Fort Worth, TX) in the treatment eye 1 minute before the procedure. After pupil dilatation by tropicamide 1% (Tropamid® FORTE; Bilim, Istanbul, Turkey), PRP was performed through Quadr Aspheric Lens (Volk Optical, Mentor, Ohio) with the help of carbomer 0.2% ophthalmic gel (Viscotears, Bausch & Lomb, İstanbul, Türkiye). PRP application was performed by a Topcon PASCAL Streamline 532 nm Green Laser (Topcon Corporation, Tokyo, Japan) device, and parameters such as power, spot size, exposure duration, and number of shots were noted after application in all patients. In the PRP sessions, to standardize the laser energy exposure between the sessions, the term photocoagulation energy (PE) was introduced (PE = (power (milliwatt) × spot size (micrometer) × exposure duration (second) × number of shots) / 10 6 ). Ramdomization To ensure drug randomization and to blind the content of the administered active substance from both the practitioner and the participant, the topical agent was transferred from its original container into an opaque, sterile, capped, and unlabeled topical dropper bottle. The active agent in the bottle was known only to the study designer. Throughout the first five days of each week, participants who were scheduled for PRP application, regardless of study design, received a specific topical NSAID or artificial tears from unlabeled, identical-looking bottles. Any active substance change was concealed from the drop administrator and the PRP performer. Subjective Pain Scoring An intensity score of the pain is provided by the Visual Analog Scale (VAS) pain score. With the VAS, a patient can rate their pain on a horizontal 0–10 grading scale of subjective pain assessment, where 0 is "no pain" and 10 is "the most severe pain" ( 13 ). The VAS form was explained to all patients immediately after PRP, and they were asked to evaluate the pain they felt during the session. In participants who underwent bilateral PRP treatment, the procedure was initiated first in the right eye, and the VAS assessment was conducted following the right eye PRP application, before initiating the procedure in the left eye. Exclusion Criteria Patients under systemic analgesic therapy for another disease, patients with vitreous hemorrhage or media opacity that would hinder PRP application, patients who were unable to express pain sensation with VAS after application, patients with active ocular infection/inflammation that would affect the study protocol, and patients who voluntarily terminated the PRP application session were excluded from the study. Statistical Analyses Statistical analyses were performed using IBM SPSS Statistics (IBM Corp., Armonk, NY, USA) version 20.0. Numerical descriptive statistics are presented as means and standard deviations for normally distributed variables. Descriptive statistics of categorical variables are presented as percentages. The Kolmogorov-Smirnov Test was used to assess the normality of the data. An Independent Sample T-Test/ Mann - Whitney U Test was used to compare two independent groups. The Analysis of Variance was used to compare more than two independent groups. The Chi-Square Test was used to compare categorical data. The significance level was considered to be P˂0.05. Results This study analyzed 270 eyes from 270 patients. Each experimental group received one of 7 different topical NSAIDs in addition to topical Proparacaine HCl 0.5%, while the control group received only artificial tears alongside topical Proparacaine HCl 0.5%. A comparison of the demographic characteristics among groups revealed no significant differences in age (P = 0.662) and gender (P = 0.997). No significant difference was observed among the groups regarding the duration of diabetes (P = 0.778). All participants in the study were diagnosed with either NPDR or PDR, with no significant differences in the distribution of DRP type among the groups (P = 0.978). The groups were compared regarding the number of previous IVIs. No significant differences were observed between the groups in terms of the number of previous IVIs administered to the PRP-treated eye (P = 0.165) or the total number of IVIs received in both eyes (P = 0.474). No significant difference was found between the groups in terms of the total number of laser shots administered to the PRP-treated eye (P = 0.655) and the total number of laser shots administered to both eyes of the patient (P = 0.524). PE is considered one of the most important parameters associated with pain sensation in this study. When comparing the total PE across all PRP sessions administered to both eyes, the total PE for all PRP sessions applied to the treated eye, and the PE of the last session for the treated eye, no significant differences were found between the groups for these three parameters (P = 0.476, P = 0.814, P = 0.813, respectively). Details are presented in Table 1 . Table 1 Distribution of patient demographics across groups and statistical analysis of demographic variation Parameter Control (34 patients) Brom (34 patients) Indo (35 patients) Diclo (33 patients) Nep3 (34 patients) Keto (34 patients) Flur (33 patients) Nep1 (33 patients) P Value Age Mean ± SD / Median (IQR) 65.5 (11.00) 63.0 (10.25) 63.0 (13.00) 64.0 (16.00) 65.0 (12.25) 63.8 ± 8.1 63.0 (10.50) 64.0 (10.50) a 0.662 Min-Max 52–75 47–85 37–76 47–85 43–77 48–78 52–76 44–77 Gender Male N, (%) 18 (52.9%) 17 (50.0%) 18 (51.4%) 17 (51.5%) 17 (50.0%) 16 (47.1%) 16 (48.5%) 19 (57.6%) b 0.997 Female N, (%) 16 (47.1%) 17 (50.0%) 17 (48.6%) 16 (48.5%) 17 (50.0%) 18 (52.9%) 17 (51.5%) 14 (42.4%) Duration of Diabetes (months) Mean ± SD / Median (IQR) 139.6 ± 122.8 150.0 (174) 132.0 (168) 144.0 (168) 178.9 ± 131.2 178.1 ± 97.2 120.0 (132) 156.0 (156) a 0.778 Min-Max 1-456 1-432 0-324 1-432 1-624 1-288 5-480 5—492 Diabetes Type NPDR N, (%) 12 (35.3%) 13 (38.2%) 13 (37.1%) 15 (45.5%) 13 (38.2%) 11 (32.4%) 11 (33.3%) 12 (36.4%) b 0.978 PDR N, (%) 22 (64.7%) 21 (61.8%) 22 (62.9%) 18 (54.5%) 21 (61.8%) 23 (67.6%) 22 (66.7%) 21 (63.6%) IVI Count, Both eyes total Median (IQR) 1 ( 3 ) 1 ( 3 ) 2 ( 4 ) 1 ( 7 ) 1 ( 3 ) 1 ( 3 ) 2 ( 3 ) 1 ( 4 ) a 0.474 Min-Max 0–18 0–21 0–15 0–32 0–13 0–18 0–22 0–11 IVI Count, PRP eye only Median (IQR) 0 ( 2 ) 0 ( 2 ) 2 ( 3 ) 1 ( 2 ) 0 ( 2 ) 0 ( 2 ) 1 ( 2 ) 1 ( 2 ) a 0.165 Min-Max 0–8 0–12 0–12 0–14 0–7 0–7 0–12 0–10 Total PRP laser shots, Both eyes total Mean ± SD / Median (IQR) 1450.0 (2388) 2240.0 (4273) 2700.0 (2300) 2200.0 (7150) 3515.0 (4549) 3355.3 ± 1818.6 2826.3 ± 1648.3 2937.2 ± 2038.7 a 0.524 Min-Max 500–9810 350–9200 1000–11265 550-11500 450–8790 500–7280 300–5750 500–9000 Total PRP laser shots, PRP eye only Mean ± SD / Median (IQR) 1400.0 (1600) 1550.0 (2306) 1800.0 (1730) 1450.0 (3820) 2105.1 ± 1339.2 1745.0 ± 860.3 1887.9 ± 866.8 1962.3 ± 1100.1 a 0.655 Min-Max 500–5050 350–4950 500–5830 550–6100 100–4840 300–3600 300–3370 500–4510 PE of both eyes total Mean ± SD / Median (IQR) 82.8 (111.75) 92.25 (192.94) 132.15 (107.10) 98.4 (318.46) 155.52 (276.12) 178.8 ± 104.8 153.8 ± 101.1 126.8 (111.51) a 0.476 Min-Max 15.0-492.6 12.6-549.1 32.0-481.8 15.4-830.7 13.5–515.0 21.0-405.6 11.7-484.8 24.0-515.1 PE of PRP eye only Mean ± SD / Median (IQR) 61.8 (90.66) 92.5 ± 74.4 96.7 ± 52.6 67.2 (126.08) 112.3 ± 75.7 94.0 ± 52.0 94.9 ± 54.3 91.65 (62.50) a 0.814 Min-Max 15.0-265.0 12.6–327.0 29.4–197.0 15.4-420.6 13.5-272.9 12.0-198.6 11.7-229.8 24.0-472.0 PE of only last session Mean ± SD / Median (IQR) 34.5 ± 9.2 31.9 ± 14.4 28.8 (20.80) 30.8 ± 18.3 36.4 ± 16.7 32.0 ± 12.8 32.4 (14.55) 28.8 (13.58) a 0.813 Min-Max 14.2–50.4 6.4–90.0 12.8–90.0 6.4–96.0 13.2–72.4 9.6–58.5 10.8–86.4 10.8–60.0 Brom = bromfenac 0.09% group; Indo = indomethacin 0.1% group; Diclo = diclofenac sodium 0.1% group; Nep3 = nepafenac 0.3% group; Keto = ketorolac trometamol 0.5% group; Flur = flurbiprofen 0.03% group; Nep1 = nepafenac %0.1 group; SD = standard deviation; IQR = interquartile range; Min = minimum; Max = maximum; N = number; IVI = intravitreal injection; PRP = panretinal photocoagulatin; PE = photocoagulation energy. Data are presented as mean ± standard deviation for normally distributed variables and median (interquartile range) for non-normally distributed variables. a Analysis of Variance Test, b Chi-Square Test The mean VAS score was higher in females than males in all participants (P 60 years, both in all participants (P < 0.001) and in the control group (P = 0.007). PRP-related pain was analyzed according to DRP type. In the NSAID-free control group and in all patients, VAS scores were higher in the PDR group than in the NPDR group (P < 0.001 for all participants; P = 0.032 for the control group). Details are presented in Table 2 . Table 2 Distribution of VAS scores according to age, gender, and DRP type of the groups and statistical analysis of these values. Number of Patients Mean ± SD/ Median (IQR) Minimum Maximum P Value Gender All participants Male 139 3.00 (4.0) 0 8 a <0.001 Female 131 4.00 (3.0) 0 10 Control group only Male 18 3.00 (2.3) 0 8 a 0.013 Female 16 5.00 (4.0) 3 10 Age All participants 60< 176 3.00 (4.0) 0 10 a <0.001 60≥ 94 4.33 ± 2.61 0 10 Control group only 60< 25 4.00 (2.0) 0 10 a 0.007 60≥ 9 8.00 (2.5) 3 9 DRP type All participants NPDR 100 2.00 (4.0) 0 10 a <0.001 PDR 170 4.00 (3.0) 0 10 Control group only NPDR 12 3.58 ± 2.23 0 8 a 0.032 PDR 22 5.00 (5.0) 2 10 SD = standard deviation; IQR = interquartile range; DRP = diabetic retinopathy; NPDR = non-proliferative diabetic retinopathy; PDR = proliferative diabetic retinopathy. Data are presented as mean ± standard deviation for normally distributed variables and median (interquartile range) for non-normally distributed variables. a Statistically significant values (Mann - Whitney U Test) The control group had the highest mean VAS score, followed by Flur, Keto, and Nep1, while Brom had the lowest, followed by Indo, Nep3, and Diclo. VAS scores in the Brom (P < 0.001), Indo (P < 0.001), Nep3 (P = 0.002), and Diclo (P = 0.029) groups were significantly lower than in the control group. Although Flur, Nep1, and Keto showed lower VAS scores than the control, the difference was not significant. NSAID analgesic effects on PRP-related pain varied by gender. In females, pain scores were significantly reduced in the Brom (P = 0.003), Indo (P = 0.009), Nep3 (P = 0.004), and Diclo (P = 0.040) groups, consistent with overall findings. In males, significant reduction occurred only in the Brom (P = 0.021) and Indo (P = 0.043) groups, while Nep3 (P = 0.477), Diclo (P = 0.795), and other NSAIDs showed no significant effect. In participants > 60 years, PRP-related pain was significantly reduced in the Brom (P = 0.001), Indo (P = 0.004), and Nep3 (P = 0.022) groups. In those ≤ 60 years, pain reduction was significant in the Brom (P = 0.026), Indo (P = 0.006), Nep3 (P = 0.025), and Diclo (P = 0.013) groups. No NSAID significantly reduced PRP-related pain in the NPDR group. In the PDR group, pain was significantly lower in the Brom (P < 0.001), Indo (P = 0.007), and Nep3 (P = 0.015) groups, while other NSAIDs showed no effect. Details are presented in Table 3 . Table 3 Statistical analysis of the mean VAS values of the groups and comparison of these values with the control group. Groups No of Pat Mean ± SD/ Median (IQR) Min- Max P Value Groups No of Pat Mean ± SD/ Median (IQR) Min- Max P Value All Patients Control 34 5.00 (4.3) 0–10 Flur 33 5.00 (4.5) 1–10 0.999 Nep1 33 3.82 ± 2.42 0–10 0.582 Keto 34 4.15 ± 2.36 0–10 0.880 Diclo 33 2.00 (4.0) 0–10 a 0.029 Nep3 34 2.00 (2.7) 0–8 a 0.002 Indo 35 2.00 (4.0) 0–7 a <0.001 Brom 34 1.75 (3.5) 0–7 a <0.001 Males Only Control 18 3.00 (2.3) 0–8 Females Only Control 16 5.00 (4.0) 3–10 Flur 17 3.00 (3.3) 1–7 0.989 Flur 16 5.88 ± 2.87 1–10 1.000 Nep1 19 3.37 ± 2.09 1–7 0.992 Nep1 14 4.43 ± 2.77 0–10 0.664 Keto 16 3.88 ± 2.53 0–8 1.000 Keto 18 4.39 ± 2.25 0–10 0.421 Diclo 17 1.76 ± 2.07 0–6 0.795 Diclo 16 2.00 (3.8) 0–10 a 0.040 Nep3 17 2.00 (4.5) 0–8 0.477 Nep3 17 3.00 (2.3) 0–8 a 0.004 Indo 18 1.00 (4.0) 0–6 a 0.043 Indo 17 3.15 ± 1.82 0–7 a 0.009 Brom 17 0.00 (2.5) 0–6 a 0.021 Brom 17 2.62 ± 2.25 0–7 a 0.003 Age 60≥ Control 9 8.00 (2.5) 3–9 Age 60< Control 25 4.00 (2.0) 0–10 Flur 11 5.18 ± 2.71 1–10 0.717 Flur 22 4.50 (4.1) 1–9 1.000 Nep1 12 5.17 ± 2.25 2–10 0.568 Nep1 21 3.05 ± 2.20 0–7 0.644 Keto 10 5.70 ± 2.50 1–10 0.928 Keto 24 3.50 ± 2.02 0–7 0.934 Diclo 13 3.31 ± 2.25 0–6 a 0.013 Diclo 20 2.88 ± 2.48 0–10 0.433 Nep3 13 3.20 ± 2.78 0–8 a 0.025 Nep3 21 2.12 ± 1.73 0-6.5 a 0.022 Indo 15 3.33 ± 1.72 0–6 a 0.006 Indo 20 1.00 (2.8) 0–7 a 0.004 Brom 11 3.09 ± 2.63 0–7 a 0.026 Brom 23 1.00 (3.0) 0–5 a 0.001 NPDR Only Control 12 3.58 ± 2.34 0–8 PDR Only Control 22 5.00 (5.0) 2–10 Flur 11 2.00 (5.0) 1–8 1.000 Flur 22 5.27 ± 2.62 1–10 0.999 Nep1 12 3.50 ± 3.03 0–10 1.000 Nep1 21 4.00 ± 2.05 1–8 0.235 Keto 11 3.55 ± 2.54 0–7 1.000 Keto 23 5.00 (2.0) 0–10 0.631 Diclo 15 1.80 ± 1.66 0–5 0.192 Diclo 18 4.08 ± 2.40 0–10 0.437 Nep3 13 1.00 (2.5) 0-6.5 0.308 Nep3 21 3.00 (3.3) 0–8 a 0.015 Indo 13 0.00 (2.5) 0–4 0.077 Indo 22 3.05 ± 2.01 0–7 a 0.007 Brom 13 1.00 (3.3) 0–7 0.715 Brom 21 2.00 (3.8) 0–6 a <0.001 No = number; Pat = patients; SD = standatd deviation; IQR = interquartile range; Min = minimum; Max = maximum; Flur = flurbiprofen 0.03%; Nep1 = nepafenac %0.1; Keto = ketorolac trometamol 0.5%; Diclo = diclofenac sodium 0.1%; Nep3 = nepafenac 0.3%; Indo = indomethacin 0.1%; Brom = bromfenac 0.09%; NPDR = non-proliferative diabetic retinopathy; PDR = proliferative diabetic retinopathy. Data are presented as mean ± standard deviation for normally distributed variables and median (interquartile range) for non-normally distributed variables. a Statistically significant results of the comparison with control group values (Analysis of Variance Test with Games-Howell Correction Post Hoc, Multiple Comparisons). Discussion This study investigates the factors affecting PRP-related pain sensation and the effectiveness of topical NSAIDs in reducing PRP-related pain. Therefore, to ensure the reliability of the results, factors that may affect the subjective perception of pain, such as age, gender, duration of diabetes mellitus, and type of DRP, were analyzed both in terms of their effect on PRP-related pain perception and their distribution within NSAID groups. Research on pain experience has shown that subjective and physiologic responses to pain may be affected by previous pain experiences. Both expectations and previous pain experience show strong relationships to current pain tolerance. Individuals with a history of greater pain tend to have lower pain tolerance ( 14 ). In light of this information, we believe that previous pain experiences by procedures that cause pain sensation in patients, such as IVI and PRP, may influence the VAS values obtained in this study. For this reason, while examining the effect of NSAIDs on VAS scores, the distribution of these parameters among the groups was also analyzed. To ensure the reliability of the results, it was desired that NSAIDs be the sole factor influencing PRP-related pain perception between the groups. In this context, no significant differences were observed among the NSAID groups with respect to age, gender, duration of diabetes, and type of diabetes. The total number of IVIs, laser shots, and the amount of PE in both the PRP-treated eye and both eyes did not differ. Additionally, no significant difference was found in the amount of PE in the last session for the PRP-treated eye. Consequently, no significant differences were identified among the groups concerning all parameters considered that may influence pain perception. In the comparison of PRP-related pain scores by gender, females exhibited significantly higher pain levels than males, irrespective of NSAID administration. Although VAS scores decreased in both groups following NSAID administration, PRP-related pain perception in females remained significantly higher than in males. Gender-related differences in subjective pain perception have been extensively investigated in previous studies, with quantitative analyses consistently demonstrating greater pain sensitivity in females ( 15 ). The findings of the present study align with the existing literature, as PRP-related pain scores were consistently higher in females across all conditions. Similarly, Esgin and Samut ( 8 ) reported significantly higher mean pain scores in females than in males among patients who underwent scatter laser photocoagulation using a 532 nm green laser, corroborating the results of this study. In contrast, Del Santo et al. ( 16 ) did not observe a significant relationship between gender and mean VAS scores in their study comparing metamizole and ibuprofen in laser photocoagulation patients. However, their study had a relatively small sample size of only 34 participants, and the mean age of male participants was significantly higher than that of females. It is likely that these two factors contributed to the divergent findings reported in their study. Age significantly influenced PRP-related pain perception. In the control group, patients > 60 years reported lower pain than those ≤ 60 years. NSAID treatment reduced pain in both groups, but younger patients still experienced significantly higher pain. Over thirty studies support that older adults have a higher pain threshold, with meta-analyses showing reduced pain sensitivity in those > 60 years ( 17 ). This study's findings confirm the trend of decreased pain sensitivity with age. In the control group that did not receive any topical analgesics, PRP-related pain was significantly higher in patients with PDR compared to those with NPDR. Although NSAID treatment effectively reduced pain in both groups, pain scores in the PDR group remained substantially higher than those in the NPDR group. This consistent difference suggests an underlying pathophysiological mechanism associated with the severity of the disease. In ischemic tissues, hypoxia, cellular damage, and lactate accumulation promote the release of inflammatory mediators such as bradykinin, prostaglandins, which lower the activation threshold of peripheral nociceptors and contribute to hyperalgesia ( 18 ). Moreover, tissue acidosis activates transient receptor potential channels and acid-sensing ion channels, further enhancing pain sensitivity under ischemic conditions ( 19 ). We, therefore, hypothesize that the greater PRP-related pain observed in the PDR group may primarily result from increased retinal tissue ischemia associated with advanced disease. Among the groups classified based on NSAID use, the lowest pain perception was observed in the Brom group, followed by the Indo, Nep3, and Diclo groups, respectively. The mean pain scores in these four groups were significantly lower than those in the control group, indicating their effectiveness in reducing PRP-related pain perception. However, no significant NSAID efficacy was observed in the Keto, Nep1, and Flur groups in reducing PRP-related pain. In females, Brom, Indo, Nep3, and Diclo significantly reduced pain compared to the control group. In males, pain reduction was only significant for Brom and Indo; however, Nep3 and Diclo showed no significant effect. Brom, Indo, and Nep3 significantly reduced pain compared to the control group in both participants ≤ 60 years and > 60 years. The Diclo group showed significant pain reduction in the overall and ≤ 60 years groups. However, in participants > 60 years, Diclo’s pain reduction fell outside the range of statistical significance. In the PDR group, Brom, Indo, and Nep3 groups were able to provide a significant pain reduction compared to the control group, unlike other NSAIDs. However, for all NSAIDs, mean VAS scores decreased in the NPDR group compared to the PDR group, but no NSAID provided a significant decrease compared to the control group. In this comparison, it is noteworthy that the analgesic efficacy of diclofenac and nepafenac 0.3% was diminished in males compared to females; that of diclofenac was reduced in individuals over 60 years of age compared to those aged 60 and under; and that nepafenac 0.3%, indomethacin, and bromfenac showed reduced effectiveness in patients with NPDR compared to those with PDR. Although these findings may initially appear questionable, it is important to note that the mean pain scores in the groups in which these NSAIDs were found to be ineffective were lower than those of the corresponding comparison groups. Previous studies have emphasized that NSAIDs tend to be more effective in individuals with higher pain sensitivity ( 20 ). Therefore, we believe that the difference in pain sensitivity between groups—reflected in the average pain scores—may have masked the efficacy of certain agents. The effect of topical NSAID applications on PRP-related subjective pain has been investigated in several studies. Weinberger et al. ( 21 ) reported that the application of sodium diclofenac 0.1% prior to PRP was effective in reducing pain and recommended its use prior to the procedure. Similarly, Aziz et al. ( 22 ) suggested in their study that PRP should be performed after the application of sodium diclofenac 0.1%. Zakrzewski et al. ( 23 ) investigated the effects of both oral and topical diclofenac in preventing pain during PRP and found oral diclofenac to be effective, while topical diclofenac had no effect. However, the participants in their study were exclusively PDR patients. Similarly, in the present study, no significant analgesic effect was observed with topical diclofenac administration in PDR patients compared to the control group, which is consistent with the findings of Zakrzewski et al. ( 23 ) Furthermore, Ramezani et al. ( 24 ) examined the analgesic effect of topical sodium diclofenac 0.1% in patients with severe non-PDR and early or high-risk PDR characteristics and reported no significant pain relief. However, as the distribution of NPDR and PDR patients was not reported in their study, their findings would align with ours if their population predominantly consisted of PDR patients. Ketorolac tromethamine 0.5% has been investigated for its analgesic effect on PRP-related pain. Esgin and Samut ( 8 ) found no significant pain relief with its use in scatter laser photocoagulation patients, a result consistent with the present study. However, Chewa et al. ( 25 ) reported pain reduction with ketorolac tromethamine 0.5%, though their study used a different administration protocol, applying the drug four times daily before the procedure and every 15 minutes for one hour before treatment. These differences in study design and application may explain the conflicting results regarding ketorolac’s efficacy. Few studies have examined the effect of topical nepafenac on PRP-related pain. Castro et al. ( 26 ) reported that nepafenac 0.1% alone, or in combination with anesthetic eye drops, did not significantly affect pain in relation to age, gender, or their combination. However, significant interactions were found between anesthetic drops and gender, and between anesthetic drops and nepafenac. Based on these findings, the study concluded that nepafenac was effective as a preemptive analgesic, especially in females. Similarly, in the present study, no significant pain relief was observed with nepafenac 0.1% alone, aligning with the mentioned study findings. To the best of our knowledge, no studies have specifically examined the analgesic effect of topical bromfenac, indomethacin, or nepafenac 0.3% in the management of PRP-related pain. Pastore et al. ( 27 ) investigated changes in vitreous prostaglandin E 2 (PGE 2 ) levels following the topical administration of bromfenac 0.09%, indomethacin 0.5%, nepafenac 0.3%, and diclofenac 0.1%. Although vitreous concentrations of NSAIDs and PGE 2 do not directly reflect their retinal concentrations, the authors noted that the analytical approach based on the established correlation between vitreous and retinal PGE 2 levels is widely accepted. Their findings indicated that diclofenac 0.1%, indomethacin 0.5%, nepafenac 0.3%, and bromfenac 0.09% achieved sufficient vitreous concentrations to reduce basal vitreous PGE 2 levels. However, the PGE 2 concentration in the diclofenac group was significantly higher than that observed with the other NSAIDs. Furthermore, compared to nepafenac 0.3%, the topical administration of indomethacin or bromfenac resulted in a more pronounced reduction in PGE 2 levels. In the present study, bromfenac 0.09%, indomethacin 0.5%, and nepafenac 0.3% were associated with lower pain scores, aligning with the findings of Pastore et al. ( 27 ) Although diclofenac 0.1% application resulted in higher pain scores compared to these three NSAIDs, a significant reduction in pain was observed across many groupings when compared to the control group. Conclusions This study investigated the demographic factors influencing subjective pain perception associated with PRP in patients with DRP and evaluated the efficacy of various topical NSAIDs in mitigating this pain. The results demonstrated that PRP-related pain perception was significantly higher among female patients and individuals aged 60 years or younger. Among the topical NSAIDs assessed, bromfenac 0.09%, indomethacin 0.5%, nepafenac 0.3%, and diclofenac 0.1% were identified as effective in reducing pain, whereas nepafenac 0.1%, ketorolac trometamol 0.5%, and flurbiprofen 0.03% did not exhibit significant analgesic efficacy. To the best of our knowledge, this is the first study to examine the effects of topical bromfenac 0.09%, indomethacin 0.5%, and nepafenac 0.3% on PRP-related pain. A notable strength of this study is its comprehensive evaluation of seven different topical agents within the same research framework. However, the primary limitation lies in the reliance on a self-reported pain assessment method, which is inherently subjective. Future studies employing larger sample sizes and incorporating objective pain evaluation methodologies will contribute to a more robust understanding of this topic. Abbreviations NSAID Non-steroidal anti-inflammatory drug PRP Pan-retinal photocoagulation VAS Visual Analog Scale PDR Proliferative diabetic retinopathy NPDR Non - proliferative diabetic retinopathy DRP Diabetic retinopathy IVI Intravitreal injection Nep1 Nepafenac %0.1 Nep3 Nepafenac %0.3 Keto Ketorolac trometamol 0.5% Diclo Diclofenac sodium 0.1% Flur Flurbiprofen 0.03% Indo Indomethacin 0.1% Brom Bromfenac 0.09% PE Photocoagulation energy PGE 2 Prostaglandin E 2 Declarations Authors' contributions A.K.S.: Conceptualization, data collection, statistical analysis, methodology, writing manuscript; T.E.: data collection; T.B.: data collection; H.G.: methodology, data collection. Funding No grants, funds, or financial support have been received. Data availability The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate The principles of the Declaration of Helsinki were followed throughout the study. Informed consent was obtained from the patients after the study design and possible outcomes were explained. The study was approved by the ethics committee of Trakya University Medical School (approval code: TÜTF-GOBAEK 2025/207). Consent for publication Not applicaple Competing interest Authors declare no competing interest. Conflict of Interest disclosure: The authors declare no conflict of interest. Grants and Funds: No grants, funds or financial support has been received for this work. No funding was received for this work from any organizations References Atlas D, Brussels. Belgium Int Diabetes Fed. 2015;33(2). Duh EJ, Sun JK, Stitt AW. Diabetic retinopathy: current understanding, mechanisms, and treatment strategies. JCI insight. 2017;2(14):e93751. https://doi.org/10.1172/jci.insight.93751 . Schwartz SS, Epstein S, Corkey BE, Grant SFA, Gavin RB III JR, et al. A unified pathophysiological construct of diabetes and its complications. Trends Endocrinol Metab. 2017;28(9):645–55. https://doi.org/10.1016/j.tem.2017.05.005 . Leasher JL, Bourne RRA, Flaxman SR, Jonas JB, Keeffe J, Naidoo K, et al. Global estimates on the number of people blind or visually impaired by diabetic retinopathy: a meta-analysis from 1990 to 2010. Diabetes Care. 2016;39(9):1643–9. https://doi.org/10.2337/dc15-2171 . Sinclair SH, Schwartz SS. Diabetic retinopathy–an underdiagnosed and undertreated inflammatory, neuro-vascular complication of diabetes. Front Endocrinol (Lausanne). 2019;10. https://doi.org/10.3389/fendo.2019.00843 . :843 2019;10:843. Stitt AW, Curtis TM, Chen M, Medina RJ, McKay GJ, Jenkins A, et al. The progress in understanding and treatment of diabetic retinopathy. Prog Retin Eye Res. 2016;51:156–86. https://doi.org/10.1016/j.preteyeres.2015.08.001 . Group DRSR. Photocoagulation treatment of proliferative diabetic retinopathy: clinical application of Diabetic Retinopathy Study (DRS) findings, DRS Report Number 8. Ophthalmology. 1981;88(7):583–600. Esgin H, Samut HS. Topical ketorolac 0.5% for ocular pain relief during scatter laser photocoagulation with 532 nm green laser. J Ocul Pharmacol Ther. 2006;22(6):460–4. https://doi.org/10.1089/jop.2006.22.460 . Johari M, Moallem M, Amini A, Sanie-Jahromi F. Pain Management Strategies before Pan-Retinal Photocoagulation for Diabetic Retinopathy: A Systematic Review. J Ophthalmol. 2024;2024(1):6662736. https://doi.org/10.1155/2024/6662736 . Camu F, Vanlersberghe C. Pharmacology of systemic analgesics. Best Pract Res Clin Anaesthesiol. 2002;16(4):475–88. https://doi.org/10.1053/bean.2002.0262 . Singh RB, Khera T, Ly V, Saini C, Cho W, Shergill S, et al. Ocular complications of perioperative anesthesia: A review. Graefe’s Arch Clin Exp Ophthalmol. 2021;259:2069–83. https://doi.org/10.1007/s00417-021-05119-x . Group DRSR. Indications for photocoagulation treatment of diabetic retinopathy: Diabetic Retinopathy Study Report 14. Int Ophthalmol Clin. 1987;27(4):239–53. https://doi.org/10.1097/00004397-198702740-00004 . Crichton N. Visual analogue scale (VAS). J Clin Nurs. 2001;10(5):706. https://doi.org/. Rollman GB, Abdel-Shaheed J, Gillespie JM, Jones KS. Does past pain influence current pain: biological and psychosocial models of sex differences. Eur J Pain. 2004;8(5):427–33. https://doi.org/10.1016/j.ejpain.2004.03.002 . Bartley EJ, Fillingim RB. Sex differences in pain: a brief review of clinical and experimental findings. Br J Anaesth. 2013;111(1):52–8. https://doi.org/10.1093/bja/aet127 . Santo AM, Del, Auge RM, Ferraz CA. Preemptive analgesia of metamizole versus ibuprofen in retinal laser photocoagulation. Rev Bras Oftalmol. 2016;75:14–7. https://doi.org/10.5935/0034-7280.20160003 . Lautenbacher S, Peters JH, Heesen M, Scheel J, Kunz M. Age changes in pain perception: A systematic-review and meta-analysis of age effects on pain and tolerance thresholds. Neurosci Biobehav Rev. 2017;75:104–13. https://doi.org/10.1016/j.neubiorev.2017.01.039 . Queme LF, Ross JL, Jankowski MP. Peripheral mechanisms of ischemic myalgia. Front Cell Neurosci. 2017;11:419. https://doi.org/10.3389/fncel.2017.00419 . Molliver DC, Immke DC, Fierro L, Paré M, Rice FL. ASIC3, an acid-sensing ion channel, is expressed in metaboreceptive sensory neurons. Mol Pain. 2005;1:35. https://doi.org/10.1186/1744-8069-1-35 . Arendt-Nielsen L, Curatolo M, Drewes A. Human experimental pain models in drug development: translational pain research. Curr Opin Investig Drugs. 2007;8(1):41–53. Weinberger D, Ron Y, Lichter H, Rosenblat I, Axer-Siegel R, Yassur Y. Analgesic effect of topical sodium diclofenac 0.1% drops during retinal laser photocoagulation. Br J Ophthalmol. 2000;84(2):135–7. https://doi.org/10.1136/bjo.84.2.135 . Aziz A, Khan Z, Khan MA, Din SA, Chaudhari MZ. Topical sodium diclofenac during pan-retinal photocoagulation in patients with proliferative diabetic retinopathy. Pakistan J Med Heal Sci. 2022;16(1):1459–62. https://doi.org/10.53350/pjmhs221611459 . Zakrzewski PA, O’Donnell HL, Lam W-C. Oral versus topical diclofenac for pain prevention during panretinal photocoagulation. Ophthalmology. 2009;116(6):1168–74. https://doi.org/10.1016/j.ophtha.2009.01.022 . Ramezani A, Entezari M, Shahbazi MM, Semnani Y, Nikkhah H, Yaseri M. Analgesic effect of topical sodium diclofenac before retinal photocoagulation for diabetic retinopathy: a randomized double-masked placebo-controlled intraindividual crossover clinical trial. Korean J Ophthalmol KJO. 2017;31(2):102. https://doi.org/10.3341/kjo.2017.31.2.102 . Chewa Raja JS, Singh S, Ismail F. Pre-emptive topical ketorolac tromethamine 0.5% for panretinal photocoagulation. J Ocul Pharmacol Ther. 2021;37(5):313–7. https://doi.org/10.1089/jop.2020.0089 . Castro EF, de Okuda S, Amatto EA, Almeida VB, Gracia HG, Kara-Junior M. Preemptive analgesia of nepafenac 0.1% in retinal photocoagulation. Rev Bras Oftalmol. 2014;73:269–72. https://doi.org/10.5935/0034-7280.20140058 . Pastore MR, De Giacinto C, Cirigliano G, D’Aloisio R, Addobbati R, Agostinis C, et al. Vitreous prostaglandin e2 changes after topical administration of diclofenac 0.1%, Indomethacin 0.5%, Nepafenac 0.3%, and Bromfenac 0.09%. Retina. 2020;40(9):1838–45. https://doi.org/10.1097/IAE.0000000000002674 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 02 Oct, 2025 Read the published version in BMC Ophthalmology → Version 1 posted Editorial decision: Revision requested 28 Jul, 2025 Reviews received at journal 26 Jul, 2025 Reviewers agreed at journal 21 Jul, 2025 Reviews received at journal 18 Jun, 2025 Reviewers agreed at journal 04 Jun, 2025 Reviewers agreed at journal 04 Jun, 2025 Reviewers invited by journal 04 Jun, 2025 Editor invited by journal 04 Jun, 2025 Editor assigned by journal 02 Jun, 2025 Submission checks completed at journal 02 Jun, 2025 First submitted to journal 31 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6790841","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":466861174,"identity":"ac46d6c9-61df-462f-a97f-27a721f074b5","order_by":0,"name":"Ahmet Kürşad SAKALLIOĞLU","email":"data:image/png;base64,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","orcid":"","institution":"Trakya University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Ahmet","middleName":"Kürşad","lastName":"SAKALLIOĞLU","suffix":""},{"id":466861175,"identity":"766de985-5e9f-4276-852d-804d8121b08c","order_by":1,"name":"Tülay ENGİN","email":"","orcid":"","institution":"Trakya University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Tülay","middleName":"","lastName":"ENGİN","suffix":""},{"id":466861176,"identity":"51b63830-1224-4ded-bd93-22adefa49712","order_by":2,"name":"Tuğçe BEK","email":"","orcid":"","institution":"Trakya University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Tuğçe","middleName":"","lastName":"BEK","suffix":""},{"id":466861177,"identity":"14d649bd-4206-415c-8e4c-5dac960bd960","order_by":3,"name":"Hande GÜÇLÜ","email":"","orcid":"","institution":"Trakya University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hande","middleName":"","lastName":"GÜÇLÜ","suffix":""}],"badges":[],"createdAt":"2025-05-31 12:08:02","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6790841/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6790841/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12886-025-04376-2","type":"published","date":"2025-10-02T15:56:56+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":92883613,"identity":"b8a4eb2e-f275-4c75-9fc4-f2ec09653679","added_by":"auto","created_at":"2025-10-06 16:05:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1188462,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6790841/v1/cd0fcc48-ecee-453f-b7bd-154703b5d043.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Analgesic efficacy of 7 different topical NSAIDs in panretinal photocoagulation-associated pain","fulltext":[{"header":"Background","content":"\u003cp\u003eDiabetes mellitus is a major global health challenge, affecting nearly 500\u0026nbsp;million individuals worldwide (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). This metabolic disorder is a significant burden on health systems due to its association with many complications (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Diabetic retinopathy (DRP) is one of the most prevalent and severe ocular complications and approximately 4.5\u0026nbsp;million people have vision impairment or blindness due to this condition (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). DRP develops due to progressive microvascular dysfunction, leading to retinal ischemia, abnormal blood vessel growth, and macular edema (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). As DRP advances to its proliferative stage, known as proliferative diabetic retinopathy (PDR), retinal ischemia and pathological neovascularization develop on the retinal surface, substantially elevating the risk of severe vision loss (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePanretinal photocoagulation (PRP) is a well-established treatment for reducing the risk of severe vision loss in patients with PDR (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Unfortunately, PRP is often a painful procedure for many patients. Pain and discomfort may hinder patients from completing PRP therapy or necessitate its early termination, potentially resulting in poor adherence to laser treatment, which is essential for the effective management of PDR (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTo minimize this discomfort during PRP, many pain-reducing molecules and application methods have been investigated in previous studies. These methods include oral, intramuscular, subtenon, peribulbar, subconjunctival, topical, and even inhalation (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). However, systemic drugs have side effects, and interventional methods have many complications that may occur during the procedure (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Considering that diabetes is a disease that affects half a billion people (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e), we believe that the number of these side effects and complications will be considerable and that these side effects and complications can be avoided to some extent with topical analgesic applications.\u003c/p\u003e \u003cp\u003eTherefore, in this study, we investigated the demographic characteristics of patients and the efficacy of topical non-steroidal anti-inflammatory drugs (NSAIDs) on PRP-related subjective pain sensation.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis single-center, cross-sectional, retrospective, placebo-controlled, comparative case series was conducted with 270 eyes of 270 patients who underwent PRP for non-proliferative diabetic retinopathy (NPDR) or PDR in a university teaching hospital. The right eyes of participants who underwent bilateral or right PRP application, and the left eyes of participants who underwent left PRP application were included in the study.\u003c/p\u003e \u003cp\u003eThe decision for PRP application was made within the indications determined by the Diabetic Retinopathy Study Research Group (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). The distinction between NPDR and PDR was made using fluorescein fundus angiography performed with the Canon CX-1 fundus camera (Canon INC., Tokyo, Japan).\u003c/p\u003e \u003cp\u003eDemographic data such as age, gender, number of previous intravitreal injections (IVIs), and previous PRP applications and parameters were noted from patient files.\u003c/p\u003e \u003cp\u003eA total of 270 eyes in 8 groups were given only one of 7 different NSAIDs in the lower conjunctival cul-de-sac of the study eye, 30 to 45 minutes before the procedure, which are: nepafenac %0.1 (Nevanac, Alcon Laboratories Ltd, Hertfordshire, UK) (Nep1 group), nepafenac 0.3% (Apfecto 0.3%, World Medicine Ophthalmics, İstanbul, Turkey) (Nep3 group), ketorolac trometamol 0.5% (Acular, Allergan Pharmaceuticals, Westport, Ireland) (Keto group), diclofenac sodium 0.1% (Inflased, Bilim, Turkey) (Diclo group), flurbiprofen 0.03% (Flubord, World Medicine Ophthalmics, İstanbul, Turkey) (Flur group), indomethacin 0.1% (Indocollyre, Bausch \u0026amp; Lomb\u0026ndash;Laboratoire Chauvin, Montpellier, France) (Indo group), bromfenac 0.09% (Yellox; Bausch \u0026amp; Lomb Swiss AG, Zug, Switzerland) (Brom group), and the control group consisted of patients who were administered artificial eye drop instead of topical NSAIDs. All patients received one topical Proparacaine HCl 0.5% eye drop (Alcaine; Alcon Laboratories, Inc., Fort Worth, TX) in the treatment eye 1 minute before the procedure.\u003c/p\u003e \u003cp\u003eAfter pupil dilatation by tropicamide 1% (Tropamid\u0026reg; FORTE; Bilim, Istanbul, Turkey), PRP was performed through Quadr Aspheric Lens (Volk Optical, Mentor, Ohio) with the help of carbomer 0.2% ophthalmic gel (Viscotears, Bausch \u0026amp; Lomb, İstanbul, T\u0026uuml;rkiye).\u003c/p\u003e \u003cp\u003ePRP application was performed by a Topcon PASCAL Streamline 532 nm Green Laser (Topcon Corporation, Tokyo, Japan) device, and parameters such as power, spot size, exposure duration, and number of shots were noted after application in all patients.\u003c/p\u003e \u003cp\u003eIn the PRP sessions, to standardize the laser energy exposure between the sessions, the term photocoagulation energy (PE) was introduced (PE = (power (milliwatt) \u0026times; spot size (micrometer) \u0026times; exposure duration (second) \u0026times; number of shots) / 10\u003csup\u003e6\u003c/sup\u003e).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eRamdomization\u003c/h2\u003e \u003cp\u003eTo ensure drug randomization and to blind the content of the administered active substance from both the practitioner and the participant, the topical agent was transferred from its original container into an opaque, sterile, capped, and unlabeled topical dropper bottle. The active agent in the bottle was known only to the study designer. Throughout the first five days of each week, participants who were scheduled for PRP application, regardless of study design, received a specific topical NSAID or artificial tears from unlabeled, identical-looking bottles. Any active substance change was concealed from the drop administrator and the PRP performer.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSubjective Pain Scoring\u003c/h3\u003e\n\u003cp\u003eAn intensity score of the pain is provided by the Visual Analog Scale (VAS) pain score. With the VAS, a patient can rate their pain on a horizontal 0\u0026ndash;10 grading scale of subjective pain assessment, where 0 is \"no pain\" and 10 is \"the most severe pain\" (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). The VAS form was explained to all patients immediately after PRP, and they were asked to evaluate the pain they felt during the session. In participants who underwent bilateral PRP treatment, the procedure was initiated first in the right eye, and the VAS assessment was conducted following the right eye PRP application, before initiating the procedure in the left eye.\u003c/p\u003e\n\u003ch3\u003eExclusion Criteria\u003c/h3\u003e\n\u003cp\u003ePatients under systemic analgesic therapy for another disease, patients with vitreous hemorrhage or media opacity that would hinder PRP application, patients who were unable to express pain sensation with VAS after application, patients with active ocular infection/inflammation that would affect the study protocol, and patients who voluntarily terminated the PRP application session were excluded from the study.\u003c/p\u003e\n\u003ch3\u003eStatistical Analyses\u003c/h3\u003e\n\u003cp\u003eStatistical analyses were performed using IBM SPSS Statistics (IBM Corp., Armonk, NY, USA) version 20.0. Numerical descriptive statistics are presented as means and standard deviations for normally distributed variables. Descriptive statistics of categorical variables are presented as percentages. The Kolmogorov-Smirnov Test was used to assess the normality of the data. An Independent Sample T-Test/ Mann - Whitney U Test was used to compare two independent groups. The Analysis of Variance was used to compare more than two independent groups. The Chi-Square Test was used to compare categorical data. The significance level was considered to be P˂0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThis study analyzed 270 eyes from 270 patients. Each experimental group received one of 7 different topical NSAIDs in addition to topical Proparacaine HCl 0.5%, while the control group received only artificial tears alongside topical Proparacaine HCl 0.5%.\u003c/p\u003e \u003cp\u003eA comparison of the demographic characteristics among groups revealed no significant differences in age (P\u0026thinsp;=\u0026thinsp;0.662) and gender (P\u0026thinsp;=\u0026thinsp;0.997).\u003c/p\u003e \u003cp\u003eNo significant difference was observed among the groups regarding the duration of diabetes (P\u0026thinsp;=\u0026thinsp;0.778). All participants in the study were diagnosed with either NPDR or PDR, with no significant differences in the distribution of DRP type among the groups (P\u0026thinsp;=\u0026thinsp;0.978).\u003c/p\u003e \u003cp\u003eThe groups were compared regarding the number of previous IVIs. No significant differences were observed between the groups in terms of the number of previous IVIs administered to the PRP-treated eye (P\u0026thinsp;=\u0026thinsp;0.165) or the total number of IVIs received in both eyes (P\u0026thinsp;=\u0026thinsp;0.474).\u003c/p\u003e \u003cp\u003eNo significant difference was found between the groups in terms of the total number of laser shots administered to the PRP-treated eye (P\u0026thinsp;=\u0026thinsp;0.655) and the total number of laser shots administered to both eyes of the patient (P\u0026thinsp;=\u0026thinsp;0.524).\u003c/p\u003e \u003cp\u003ePE is considered one of the most important parameters associated with pain sensation in this study. When comparing the total PE across all PRP sessions administered to both eyes, the total PE for all PRP sessions applied to the treated eye, and the PE of the last session for the treated eye, no significant differences were found between the groups for these three parameters (P\u0026thinsp;=\u0026thinsp;0.476, P\u0026thinsp;=\u0026thinsp;0.814, P\u0026thinsp;=\u0026thinsp;0.813, respectively). Details are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDistribution of patient demographics across groups and statistical analysis of demographic variation\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"14\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003cp\u003e(34 patients)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eBrom\u003c/p\u003e \u003cp\u003e(34 patients)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eIndo\u003c/p\u003e \u003cp\u003e(35 patients)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eDiclo\u003c/p\u003e \u003cp\u003e(33 patients)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNep3\u003c/p\u003e \u003cp\u003e(34 patients)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eKeto\u003c/p\u003e \u003cp\u003e(34 patients)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eFlur\u003c/p\u003e \u003cp\u003e(33 patients)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNep1\u003c/p\u003e \u003cp\u003e(33 patients)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e \u003cp\u003eP Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD / Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e65.5 (11.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e63.0 (10.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e63.0 (13.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e64.0 (16.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e65.0 (12.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e63.8\u0026thinsp;\u0026plusmn;\u0026thinsp;8.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e63.0 (10.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e64.0 (10.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.662\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eMin-Max\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e52\u0026ndash;75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e47\u0026ndash;85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e37\u0026ndash;76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e47\u0026ndash;85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e43\u0026ndash;77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e48\u0026ndash;78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e52\u0026ndash;76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e44\u0026ndash;77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" morerows=\"1\" nameend=\"c3\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMale N, (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18 (52.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e17 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e18 (51.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e17 (51.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e17 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e16 (47.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e16 (48.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e19 (57.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003csup\u003eb\u003c/sup\u003e 0.997\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eFemale N, (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16 (47.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e17 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e17 (48.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e16 (48.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e17 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e18 (52.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e17 (51.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e14 (42.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" morerows=\"1\" nameend=\"c4\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eDuration of Diabetes (months)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD / Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e139.6\u0026thinsp;\u0026plusmn;\u0026thinsp;122.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e150.0 (174)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e132.0 (168)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e144.0 (168)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e178.9\u0026thinsp;\u0026plusmn;\u0026thinsp;131.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e178.1\u0026thinsp;\u0026plusmn;\u0026thinsp;97.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e120.0 (132)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e156.0 (156)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.778\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMin-Max\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1-456\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1-432\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0-324\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1-432\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1-624\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1-288\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e5-480\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e5\u0026mdash;492\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" morerows=\"1\" nameend=\"c3\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eDiabetes Type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eNPDR N, (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12 (35.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e13 (38.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e13 (37.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e15 (45.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e13 (38.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e11 (32.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e11 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e12 (36.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003csup\u003eb\u003c/sup\u003e 0.978\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003ePDR N, (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22 (64.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e21 (61.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e22 (62.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e18 (54.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e21 (61.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e23 (67.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e22 (66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e21 (63.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" morerows=\"1\" nameend=\"c4\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eIVI Count, Both eyes total\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1 (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2 (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1 (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1 (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1 (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2 (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e1 (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.474\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMin-Max\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u0026ndash;21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u0026ndash;15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u0026ndash;32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0\u0026ndash;13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0\u0026ndash;18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0\u0026ndash;22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u0026ndash;11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" morerows=\"1\" nameend=\"c4\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eIVI Count,\u003c/p\u003e \u003cp\u003ePRP eye only\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2 (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e1 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e1 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.165\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMin-Max\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u0026ndash;12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u0026ndash;12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u0026ndash;14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0\u0026ndash;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0\u0026ndash;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0\u0026ndash;12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" morerows=\"1\" nameend=\"c4\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eTotal PRP laser shots, Both eyes total\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD / Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1450.0\u003c/p\u003e \u003cp\u003e(2388)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2240.0\u003c/p\u003e \u003cp\u003e(4273)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2700.0\u003c/p\u003e \u003cp\u003e(2300)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2200.0\u003c/p\u003e \u003cp\u003e(7150)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3515.0\u003c/p\u003e \u003cp\u003e(4549)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e3355.3\u003c/p\u003e \u003cp\u003e\u0026plusmn;\u0026thinsp;1818.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2826.3\u003c/p\u003e \u003cp\u003e\u0026plusmn;\u0026thinsp;1648.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e2937.2\u003c/p\u003e \u003cp\u003e\u0026plusmn;\u0026thinsp;2038.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.524\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMin-Max\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e500\u0026ndash;9810\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e350\u0026ndash;9200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1000\u0026ndash;11265\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e550-11500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e450\u0026ndash;8790\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e500\u0026ndash;7280\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e300\u0026ndash;5750\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e500\u0026ndash;9000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" morerows=\"1\" nameend=\"c4\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eTotal PRP laser shots, PRP eye only\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD / Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1400.0\u003c/p\u003e \u003cp\u003e(1600)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1550.0\u003c/p\u003e \u003cp\u003e(2306)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1800.0\u003c/p\u003e \u003cp\u003e(1730)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1450.0\u003c/p\u003e \u003cp\u003e(3820)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2105.1\u003c/p\u003e \u003cp\u003e\u0026plusmn;\u0026thinsp;1339.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1745.0\u003c/p\u003e \u003cp\u003e\u0026plusmn;\u0026thinsp;860.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e1887.9\u003c/p\u003e \u003cp\u003e\u0026plusmn;\u0026thinsp;866.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e1962.3\u003c/p\u003e \u003cp\u003e\u0026plusmn;\u0026thinsp;1100.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.655\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMin-Max\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e500\u0026ndash;5050\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e350\u0026ndash;4950\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e500\u0026ndash;5830\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e550\u0026ndash;6100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e100\u0026ndash;4840\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e300\u0026ndash;3600\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e300\u0026ndash;3370\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e500\u0026ndash;4510\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" morerows=\"1\" nameend=\"c4\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003ePE of\u003c/p\u003e \u003cp\u003eboth eyes total\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD /\u003c/p\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e82.8 (111.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e92.25 (192.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e132.15 (107.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e98.4 (318.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e155.52 (276.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e178.8\u0026thinsp;\u0026plusmn;\u0026thinsp;104.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e153.8\u0026thinsp;\u0026plusmn;\u0026thinsp;101.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e126.8 (111.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.476\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMin-Max\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15.0-492.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12.6-549.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e32.0-481.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e15.4-830.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e13.5\u0026ndash;515.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e21.0-405.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e11.7-484.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e24.0-515.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" morerows=\"1\" nameend=\"c4\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003ePE of PRP eye only\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD / Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e61.8\u003c/p\u003e \u003cp\u003e(90.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e92.5\u003c/p\u003e \u003cp\u003e\u0026plusmn;\u0026thinsp;74.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e96.7\u003c/p\u003e \u003cp\u003e\u0026plusmn;\u0026thinsp;52.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e67.2 (126.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e112.3\u003c/p\u003e \u003cp\u003e\u0026plusmn;\u0026thinsp;75.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e94.0\u003c/p\u003e \u003cp\u003e\u0026plusmn;\u0026thinsp;52.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e94.9\u003c/p\u003e \u003cp\u003e\u0026plusmn;\u0026thinsp;54.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e91.65 (62.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.814\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMin-Max\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15.0-265.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12.6\u0026ndash;327.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e29.4\u0026ndash;197.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e15.4-420.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e13.5-272.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e12.0-198.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e11.7-229.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e24.0-472.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" morerows=\"1\" nameend=\"c4\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003ePE of only last session\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD / Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e34.5\u0026thinsp;\u0026plusmn;\u0026thinsp;9.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e31.9\u0026thinsp;\u0026plusmn;\u0026thinsp;14.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e28.8 (20.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e30.8\u0026thinsp;\u0026plusmn;\u0026thinsp;18.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e36.4\u0026thinsp;\u0026plusmn;\u0026thinsp;16.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e32.0\u0026thinsp;\u0026plusmn;\u0026thinsp;12.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e32.4 (14.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e28.8 (13.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.813\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMin-Max\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14.2\u0026ndash;50.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.4\u0026ndash;90.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e12.8\u0026ndash;90.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e6.4\u0026ndash;96.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e13.2\u0026ndash;72.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e9.6\u0026ndash;58.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e10.8\u0026ndash;86.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e10.8\u0026ndash;60.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"14\"\u003eBrom\u0026thinsp;=\u0026thinsp;bromfenac 0.09% group; Indo\u0026thinsp;=\u0026thinsp;indomethacin 0.1% group; Diclo\u0026thinsp;=\u0026thinsp;diclofenac sodium 0.1% group; Nep3\u0026thinsp;=\u0026thinsp;nepafenac 0.3% group; Keto\u0026thinsp;=\u0026thinsp;ketorolac trometamol 0.5% group; Flur\u0026thinsp;=\u0026thinsp;flurbiprofen 0.03% group; Nep1\u0026thinsp;=\u0026thinsp;nepafenac %0.1 group; SD\u0026thinsp;=\u0026thinsp;standard deviation; IQR\u0026thinsp;=\u0026thinsp;interquartile range; Min\u0026thinsp;=\u0026thinsp;minimum; Max\u0026thinsp;=\u0026thinsp;maximum; N\u0026thinsp;=\u0026thinsp;number; IVI\u0026thinsp;=\u0026thinsp;intravitreal injection; PRP\u0026thinsp;=\u0026thinsp;panretinal photocoagulatin; PE\u0026thinsp;=\u0026thinsp;photocoagulation energy.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"14\"\u003eData are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation for normally distributed variables and median (interquartile range) for non-normally distributed variables.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"14\"\u003e\u003csup\u003ea\u003c/sup\u003e Analysis of Variance Test, \u003csup\u003eb\u003c/sup\u003e Chi-Square Test\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe mean VAS score was higher in females than males in all participants (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and the control group (P\u0026thinsp;=\u0026thinsp;0.013). Also, the mean VAS score was significantly higher in patients\u0026thinsp;\u0026le;\u0026thinsp;60 years than in patients\u0026thinsp;\u0026gt;\u0026thinsp;60 years, both in all participants (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and in the control group (P\u0026thinsp;=\u0026thinsp;0.007). PRP-related pain was analyzed according to DRP type. In the NSAID-free control group and in all patients, VAS scores were higher in the PDR group than in the NPDR group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001 for all participants; P\u0026thinsp;=\u0026thinsp;0.032 for the control group). Details are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDistribution of VAS scores according to age, gender, and DRP type of the groups and statistical analysis of these values.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNumber of Patients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD/\u003c/p\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMinimum\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMaximum\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eP Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAll participants\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e139\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e3.00 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e \u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e131\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e4.00 (3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eControl group only\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e3.00 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e5.00 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAll participants\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60\u0026lt;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e176\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e3.00 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e \u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60\u0026ge;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e4.33\u0026thinsp;\u0026plusmn;\u0026thinsp;2.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eControl group only\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60\u0026lt;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e4.00 (2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60\u0026ge;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e8.00 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eDRP type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAll participants\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNPDR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e2.00 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e \u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePDR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e170\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e4.00 (3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eControl group only\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNPDR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e3.58\u0026thinsp;\u0026plusmn;\u0026thinsp;2.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.032\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePDR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e5.00 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eSD\u0026thinsp;=\u0026thinsp;standard deviation; IQR\u0026thinsp;=\u0026thinsp;interquartile range; DRP\u0026thinsp;=\u0026thinsp;diabetic retinopathy; NPDR\u0026thinsp;=\u0026thinsp;non-proliferative diabetic retinopathy; PDR\u0026thinsp;=\u0026thinsp;proliferative diabetic retinopathy.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eData are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation for normally distributed variables and median (interquartile range) for non-normally distributed variables.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003e\u003csup\u003ea\u003c/sup\u003e Statistically significant values (Mann - Whitney U Test)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe control group had the highest mean VAS score, followed by Flur, Keto, and Nep1, while Brom had the lowest, followed by Indo, Nep3, and Diclo. VAS scores in the Brom (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), Indo (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), Nep3 (P\u0026thinsp;=\u0026thinsp;0.002), and Diclo (P\u0026thinsp;=\u0026thinsp;0.029) groups were significantly lower than in the control group. Although Flur, Nep1, and Keto showed lower VAS scores than the control, the difference was not significant.\u003c/p\u003e \u003cp\u003eNSAID analgesic effects on PRP-related pain varied by gender. In females, pain scores were significantly reduced in the Brom (P\u0026thinsp;=\u0026thinsp;0.003), Indo (P\u0026thinsp;=\u0026thinsp;0.009), Nep3 (P\u0026thinsp;=\u0026thinsp;0.004), and Diclo (P\u0026thinsp;=\u0026thinsp;0.040) groups, consistent with overall findings. In males, significant reduction occurred only in the Brom (P\u0026thinsp;=\u0026thinsp;0.021) and Indo (P\u0026thinsp;=\u0026thinsp;0.043) groups, while Nep3 (P\u0026thinsp;=\u0026thinsp;0.477), Diclo (P\u0026thinsp;=\u0026thinsp;0.795), and other NSAIDs showed no significant effect.\u003c/p\u003e \u003cp\u003eIn participants\u0026thinsp;\u0026gt;\u0026thinsp;60 years, PRP-related pain was significantly reduced in the Brom (P\u0026thinsp;=\u0026thinsp;0.001), Indo (P\u0026thinsp;=\u0026thinsp;0.004), and Nep3 (P\u0026thinsp;=\u0026thinsp;0.022) groups. In those\u0026thinsp;\u0026le;\u0026thinsp;60 years, pain reduction was significant in the Brom (P\u0026thinsp;=\u0026thinsp;0.026), Indo (P\u0026thinsp;=\u0026thinsp;0.006), Nep3 (P\u0026thinsp;=\u0026thinsp;0.025), and Diclo (P\u0026thinsp;=\u0026thinsp;0.013) groups.\u003c/p\u003e \u003cp\u003eNo NSAID significantly reduced PRP-related pain in the NPDR group. In the PDR group, pain was significantly lower in the Brom (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), Indo (P\u0026thinsp;=\u0026thinsp;0.007), and Nep3 (P\u0026thinsp;=\u0026thinsp;0.015) groups, while other NSAIDs showed no effect. Details are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eStatistical analysis of the mean VAS values of the groups and comparison of these values with the control group.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"14\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroups\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo of Pat\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD/\u003c/p\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMin-\u003c/p\u003e \u003cp\u003eMax\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP Value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eGroups\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo of Pat\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD/\u003c/p\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003eMin-\u003c/p\u003e \u003cp\u003eMax\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e \u003cp\u003eP Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003eAll Patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e5.00 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFlur\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e5.00 (4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNep1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e3.82\u0026thinsp;\u0026plusmn;\u0026thinsp;2.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.582\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eKeto\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e4.15\u0026thinsp;\u0026plusmn;\u0026thinsp;2.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.880\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiclo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e2.00 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.029\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNep3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e2.00 (2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e2.00 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e \u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBrom\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1.75 (3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e \u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003eMales Only\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e3.00 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003eFemales Only\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e5.00 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e3\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFlur\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e3.00 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u0026ndash;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.989\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFlur\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e5.88\u0026thinsp;\u0026plusmn;\u0026thinsp;2.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e1\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNep1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e3.37\u0026thinsp;\u0026plusmn;\u0026thinsp;2.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u0026ndash;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.992\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNep1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e4.43\u0026thinsp;\u0026plusmn;\u0026thinsp;2.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.664\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eKeto\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e3.88\u0026thinsp;\u0026plusmn;\u0026thinsp;2.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eKeto\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e4.39\u0026thinsp;\u0026plusmn;\u0026thinsp;2.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.421\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiclo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1.76\u0026thinsp;\u0026plusmn;\u0026thinsp;2.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.795\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eDiclo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2.00 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.040\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNep3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e2.00 (4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.477\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNep3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e3.00 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u0026ndash;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1.00 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.043\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eIndo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e3.15\u0026thinsp;\u0026plusmn;\u0026thinsp;1.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u0026ndash;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.009\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBrom\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.00 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eBrom\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2.62\u0026thinsp;\u0026plusmn;\u0026thinsp;2.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u0026ndash;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003eAge 60\u0026ge;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e8.00 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u0026ndash;9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003eAge 60\u0026lt;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e4.00 (2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFlur\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e5.18\u0026thinsp;\u0026plusmn;\u0026thinsp;2.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.717\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFlur\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e4.50 (4.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e1\u0026ndash;9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNep1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e5.17\u0026thinsp;\u0026plusmn;\u0026thinsp;2.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.568\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNep1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e3.05\u0026thinsp;\u0026plusmn;\u0026thinsp;2.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u0026ndash;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.644\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eKeto\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e5.70\u0026thinsp;\u0026plusmn;\u0026thinsp;2.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.928\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eKeto\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e3.50\u0026thinsp;\u0026plusmn;\u0026thinsp;2.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u0026ndash;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.934\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiclo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e3.31\u0026thinsp;\u0026plusmn;\u0026thinsp;2.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eDiclo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2.88\u0026thinsp;\u0026plusmn;\u0026thinsp;2.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.433\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNep3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e3.20\u0026thinsp;\u0026plusmn;\u0026thinsp;2.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNep3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2.12\u0026thinsp;\u0026plusmn;\u0026thinsp;1.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0-6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.022\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e3.33\u0026thinsp;\u0026plusmn;\u0026thinsp;1.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eIndo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e1.00 (2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u0026ndash;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBrom\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e3.09\u0026thinsp;\u0026plusmn;\u0026thinsp;2.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eBrom\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e1.00 (3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u0026ndash;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003eNPDR Only\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e3.58\u0026thinsp;\u0026plusmn;\u0026thinsp;2.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003ePDR Only\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e5.00 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e2\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFlur\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e2.00 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u0026ndash;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFlur\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e5.27\u0026thinsp;\u0026plusmn;\u0026thinsp;2.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e1\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNep1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e3.50\u0026thinsp;\u0026plusmn;\u0026thinsp;3.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNep1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e4.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e1\u0026ndash;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.235\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eKeto\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e3.55\u0026thinsp;\u0026plusmn;\u0026thinsp;2.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eKeto\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e5.00 (2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.631\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiclo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1.80\u0026thinsp;\u0026plusmn;\u0026thinsp;1.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.192\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eDiclo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e4.08\u0026thinsp;\u0026plusmn;\u0026thinsp;2.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.437\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNep3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1.00 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0-6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.308\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNep3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e3.00 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u0026ndash;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.015\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.00 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.077\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eIndo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e3.05\u0026thinsp;\u0026plusmn;\u0026thinsp;2.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u0026ndash;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBrom\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1.00 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u0026ndash;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.715\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eBrom\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2.00 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0\u0026ndash;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e \u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"14\"\u003eNo\u0026thinsp;=\u0026thinsp;number; Pat\u0026thinsp;=\u0026thinsp;patients; SD\u0026thinsp;=\u0026thinsp;standatd deviation; IQR\u0026thinsp;=\u0026thinsp;interquartile range; Min\u0026thinsp;=\u0026thinsp;minimum; Max\u0026thinsp;=\u0026thinsp;maximum; Flur\u0026thinsp;=\u0026thinsp;flurbiprofen 0.03%; Nep1\u0026thinsp;=\u0026thinsp;nepafenac %0.1; Keto\u0026thinsp;=\u0026thinsp;ketorolac trometamol 0.5%; Diclo\u0026thinsp;=\u0026thinsp;diclofenac sodium 0.1%; Nep3\u0026thinsp;=\u0026thinsp;nepafenac 0.3%; Indo\u0026thinsp;=\u0026thinsp;indomethacin 0.1%; Brom\u0026thinsp;=\u0026thinsp;bromfenac 0.09%; NPDR\u0026thinsp;=\u0026thinsp;non-proliferative diabetic retinopathy; PDR\u0026thinsp;=\u0026thinsp;proliferative diabetic retinopathy.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"14\"\u003eData are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation for normally distributed variables and median (interquartile range) for non-normally distributed variables.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"14\"\u003e\u003csup\u003ea\u003c/sup\u003e Statistically significant results of the comparison with control group values (Analysis of Variance Test with Games-Howell Correction Post Hoc, Multiple Comparisons).\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study investigates the factors affecting PRP-related pain sensation and the effectiveness of topical NSAIDs in reducing PRP-related pain. Therefore, to ensure the reliability of the results, factors that may affect the subjective perception of pain, such as age, gender, duration of diabetes mellitus, and type of DRP, were analyzed both in terms of their effect on PRP-related pain perception and their distribution within NSAID groups.\u003c/p\u003e \u003cp\u003eResearch on pain experience has shown that subjective and physiologic responses to pain may be affected by previous pain experiences. Both expectations and previous pain experience show strong relationships to current pain tolerance. Individuals with a history of greater pain tend to have lower pain tolerance (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). In light of this information, we believe that previous pain experiences by procedures that cause pain sensation in patients, such as IVI and PRP, may influence the VAS values obtained in this study. For this reason, while examining the effect of NSAIDs on VAS scores, the distribution of these parameters among the groups was also analyzed. To ensure the reliability of the results, it was desired that NSAIDs be the sole factor influencing PRP-related pain perception between the groups.\u003c/p\u003e \u003cp\u003eIn this context, no significant differences were observed among the NSAID groups with respect to age, gender, duration of diabetes, and type of diabetes. The total number of IVIs, laser shots, and the amount of PE in both the PRP-treated eye and both eyes did not differ. Additionally, no significant difference was found in the amount of PE in the last session for the PRP-treated eye. Consequently, no significant differences were identified among the groups concerning all parameters considered that may influence pain perception.\u003c/p\u003e \u003cp\u003eIn the comparison of PRP-related pain scores by gender, females exhibited significantly higher pain levels than males, irrespective of NSAID administration. Although VAS scores decreased in both groups following NSAID administration, PRP-related pain perception in females remained significantly higher than in males. Gender-related differences in subjective pain perception have been extensively investigated in previous studies, with quantitative analyses consistently demonstrating greater pain sensitivity in females (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). The findings of the present study align with the existing literature, as PRP-related pain scores were consistently higher in females across all conditions. Similarly, Esgin and Samut (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) reported significantly higher mean pain scores in females than in males among patients who underwent scatter laser photocoagulation using a 532 nm green laser, corroborating the results of this study. In contrast, Del Santo et al. (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) did not observe a significant relationship between gender and mean VAS scores in their study comparing metamizole and ibuprofen in laser photocoagulation patients. However, their study had a relatively small sample size of only 34 participants, and the mean age of male participants was significantly higher than that of females. It is likely that these two factors contributed to the divergent findings reported in their study.\u003c/p\u003e \u003cp\u003eAge significantly influenced PRP-related pain perception. In the control group, patients\u0026thinsp;\u0026gt;\u0026thinsp;60 years reported lower pain than those\u0026thinsp;\u0026le;\u0026thinsp;60 years. NSAID treatment reduced pain in both groups, but younger patients still experienced significantly higher pain. Over thirty studies support that older adults have a higher pain threshold, with meta-analyses showing reduced pain sensitivity in those\u0026thinsp;\u0026gt;\u0026thinsp;60 years (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). This study's findings confirm the trend of decreased pain sensitivity with age.\u003c/p\u003e \u003cp\u003eIn the control group that did not receive any topical analgesics, PRP-related pain was significantly higher in patients with PDR compared to those with NPDR. Although NSAID treatment effectively reduced pain in both groups, pain scores in the PDR group remained substantially higher than those in the NPDR group. This consistent difference suggests an underlying pathophysiological mechanism associated with the severity of the disease. In ischemic tissues, hypoxia, cellular damage, and lactate accumulation promote the release of inflammatory mediators such as bradykinin, prostaglandins, which lower the activation threshold of peripheral nociceptors and contribute to hyperalgesia (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Moreover, tissue acidosis activates transient receptor potential channels and acid-sensing ion channels, further enhancing pain sensitivity under ischemic conditions (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). We, therefore, hypothesize that the greater PRP-related pain observed in the PDR group may primarily result from increased retinal tissue ischemia associated with advanced disease.\u003c/p\u003e \u003cp\u003e Among the groups classified based on NSAID use, the lowest pain perception was observed in the Brom group, followed by the Indo, Nep3, and Diclo groups, respectively. The mean pain scores in these four groups were significantly lower than those in the control group, indicating their effectiveness in reducing PRP-related pain perception. However, no significant NSAID efficacy was observed in the Keto, Nep1, and Flur groups in reducing PRP-related pain.\u003c/p\u003e \u003cp\u003eIn females, Brom, Indo, Nep3, and Diclo significantly reduced pain compared to the control group. In males, pain reduction was only significant for Brom and Indo; however, Nep3 and Diclo showed no significant effect.\u003c/p\u003e \u003cp\u003eBrom, Indo, and Nep3 significantly reduced pain compared to the control group in both participants\u0026thinsp;\u0026le;\u0026thinsp;60 years and \u0026gt;\u0026thinsp;60 years. The Diclo group showed significant pain reduction in the overall and \u0026le;\u0026thinsp;60 years groups. However, in participants\u0026thinsp;\u0026gt;\u0026thinsp;60 years, Diclo\u0026rsquo;s pain reduction fell outside the range of statistical significance.\u003c/p\u003e \u003cp\u003eIn the PDR group, Brom, Indo, and Nep3 groups were able to provide a significant pain reduction compared to the control group, unlike other NSAIDs. However, for all NSAIDs, mean VAS scores decreased in the NPDR group compared to the PDR group, but no NSAID provided a significant decrease compared to the control group.\u003c/p\u003e \u003cp\u003eIn this comparison, it is noteworthy that the analgesic efficacy of diclofenac and nepafenac 0.3% was diminished in males compared to females; that of diclofenac was reduced in individuals over 60 years of age compared to those aged 60 and under; and that nepafenac 0.3%, indomethacin, and bromfenac showed reduced effectiveness in patients with NPDR compared to those with PDR. Although these findings may initially appear questionable, it is important to note that the mean pain scores in the groups in which these NSAIDs were found to be ineffective were lower than those of the corresponding comparison groups. Previous studies have emphasized that NSAIDs tend to be more effective in individuals with higher pain sensitivity (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Therefore, we believe that the difference in pain sensitivity between groups\u0026mdash;reflected in the average pain scores\u0026mdash;may have masked the efficacy of certain agents.\u003c/p\u003e \u003cp\u003eThe effect of topical NSAID applications on PRP-related subjective pain has been investigated in several studies. Weinberger et al. (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) reported that the application of sodium diclofenac 0.1% prior to PRP was effective in reducing pain and recommended its use prior to the procedure. Similarly, Aziz et al. (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) suggested in their study that PRP should be performed after the application of sodium diclofenac 0.1%. Zakrzewski et al. (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) investigated the effects of both oral and topical diclofenac in preventing pain during PRP and found oral diclofenac to be effective, while topical diclofenac had no effect. However, the participants in their study were exclusively PDR patients. Similarly, in the present study, no significant analgesic effect was observed with topical diclofenac administration in PDR patients compared to the control group, which is consistent with the findings of Zakrzewski et al. (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) Furthermore, Ramezani et al. (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) examined the analgesic effect of topical sodium diclofenac 0.1% in patients with severe non-PDR and early or high-risk PDR characteristics and reported no significant pain relief. However, as the distribution of NPDR and PDR patients was not reported in their study, their findings would align with ours if their population predominantly consisted of PDR patients.\u003c/p\u003e \u003cp\u003eKetorolac tromethamine 0.5% has been investigated for its analgesic effect on PRP-related pain. Esgin and Samut (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) found no significant pain relief with its use in scatter laser photocoagulation patients, a result consistent with the present study. However, Chewa et al. (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) reported pain reduction with ketorolac tromethamine 0.5%, though their study used a different administration protocol, applying the drug four times daily before the procedure and every 15 minutes for one hour before treatment. These differences in study design and application may explain the conflicting results regarding ketorolac\u0026rsquo;s efficacy.\u003c/p\u003e \u003cp\u003eFew studies have examined the effect of topical nepafenac on PRP-related pain. Castro et al. (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e) reported that nepafenac 0.1% alone, or in combination with anesthetic eye drops, did not significantly affect pain in relation to age, gender, or their combination. However, significant interactions were found between anesthetic drops and gender, and between anesthetic drops and nepafenac. Based on these findings, the study concluded that nepafenac was effective as a preemptive analgesic, especially in females. Similarly, in the present study, no significant pain relief was observed with nepafenac 0.1% alone, aligning with the mentioned study findings.\u003c/p\u003e \u003cp\u003eTo the best of our knowledge, no studies have specifically examined the analgesic effect of topical bromfenac, indomethacin, or nepafenac 0.3% in the management of PRP-related pain. Pastore et al. (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e) investigated changes in vitreous prostaglandin E\u003csub\u003e2\u003c/sub\u003e (PGE\u003csub\u003e2\u003c/sub\u003e) levels following the topical administration of bromfenac 0.09%, indomethacin 0.5%, nepafenac 0.3%, and diclofenac 0.1%. Although vitreous concentrations of NSAIDs and PGE\u003csub\u003e2\u003c/sub\u003e do not directly reflect their retinal concentrations, the authors noted that the analytical approach based on the established correlation between vitreous and retinal PGE\u003csub\u003e2\u003c/sub\u003e levels is widely accepted. Their findings indicated that diclofenac 0.1%, indomethacin 0.5%, nepafenac 0.3%, and bromfenac 0.09% achieved sufficient vitreous concentrations to reduce basal vitreous PGE\u003csub\u003e2\u003c/sub\u003e levels. However, the PGE\u003csub\u003e2\u003c/sub\u003e concentration in the diclofenac group was significantly higher than that observed with the other NSAIDs. Furthermore, compared to nepafenac 0.3%, the topical administration of indomethacin or bromfenac resulted in a more pronounced reduction in PGE\u003csub\u003e2\u003c/sub\u003e levels. In the present study, bromfenac 0.09%, indomethacin 0.5%, and nepafenac 0.3% were associated with lower pain scores, aligning with the findings of Pastore et al. (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e) Although diclofenac 0.1% application resulted in higher pain scores compared to these three NSAIDs, a significant reduction in pain was observed across many groupings when compared to the control group.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study investigated the demographic factors influencing subjective pain perception associated with PRP in patients with DRP and evaluated the efficacy of various topical NSAIDs in mitigating this pain. The results demonstrated that PRP-related pain perception was significantly higher among female patients and individuals aged 60 years or younger. Among the topical NSAIDs assessed, bromfenac 0.09%, indomethacin 0.5%, nepafenac 0.3%, and diclofenac 0.1% were identified as effective in reducing pain, whereas nepafenac 0.1%, ketorolac trometamol 0.5%, and flurbiprofen 0.03% did not exhibit significant analgesic efficacy.\u003c/p\u003e \u003cp\u003eTo the best of our knowledge, this is the first study to examine the effects of topical bromfenac 0.09%, indomethacin 0.5%, and nepafenac 0.3% on PRP-related pain. A notable strength of this study is its comprehensive evaluation of seven different topical agents within the same research framework. However, the primary limitation lies in the reliance on a self-reported pain assessment method, which is inherently subjective. Future studies employing larger sample sizes and incorporating objective pain evaluation methodologies will contribute to a more robust understanding of this topic.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eNSAID\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNon-steroidal anti-inflammatory drug\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003ePRP\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePan-retinal photocoagulation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eVAS\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eVisual Analog Scale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003ePDR\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eProliferative diabetic retinopathy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eNPDR\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNon - proliferative diabetic retinopathy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eDRP\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDiabetic retinopathy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eIVI\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIntravitreal injection\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eNep1\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNepafenac %0.1\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eNep3\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNepafenac %0.3\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eKeto\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eKetorolac trometamol 0.5%\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eDiclo\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDiclofenac sodium 0.1%\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eFlur\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eFlurbiprofen 0.03%\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eIndo\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIndomethacin 0.1%\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eBrom\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBromfenac 0.09%\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003ePE\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePhotocoagulation energy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003ePGE\u003c/b\u003e\u003csub\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sub\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eProstaglandin E\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA.K.S.: Conceptualization, data collection, statistical analysis, methodology, writing manuscript; T.E.: data collection; T.B.: data collection; H.G.: methodology, data collection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo grants, funds, or financial support have been received.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe principles of the Declaration of Helsinki were followed throughout the study. Informed consent was obtained from the patients after the study design and possible outcomes were explained. The study was approved by the ethics committee of Trakya University Medical School (approval code: T\u0026Uuml;TF-GOBAEK 2025/207).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicaple\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAuthors declare no competing interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest disclosure:\u0026nbsp;\u003c/strong\u003eThe authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGrants and Funds:\u0026nbsp;\u003c/strong\u003eNo grants, funds or financial support has been received for this work. No funding was received for this work from any organizations\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAtlas D, Brussels. Belgium Int Diabetes Fed. 2015;33(2).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDuh EJ, Sun JK, Stitt AW. Diabetic retinopathy: current understanding, mechanisms, and treatment strategies. JCI insight. 2017;2(14):e93751. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1172/jci.insight.93751\u003c/span\u003e\u003cspan address=\"10.1172/jci.insight.93751\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchwartz SS, Epstein S, Corkey BE, Grant SFA, Gavin RB III JR, et al. A unified pathophysiological construct of diabetes and its complications. Trends Endocrinol Metab. 2017;28(9):645\u0026ndash;55. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.tem.2017.05.005\u003c/span\u003e\u003cspan address=\"10.1016/j.tem.2017.05.005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLeasher JL, Bourne RRA, Flaxman SR, Jonas JB, Keeffe J, Naidoo K, et al. Global estimates on the number of people blind or visually impaired by diabetic retinopathy: a meta-analysis from 1990 to 2010. Diabetes Care. 2016;39(9):1643\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2337/dc15-2171\u003c/span\u003e\u003cspan address=\"10.2337/dc15-2171\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSinclair SH, Schwartz SS. Diabetic retinopathy\u0026ndash;an underdiagnosed and undertreated inflammatory, neuro-vascular complication of diabetes. Front Endocrinol (Lausanne). 2019;10. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/fendo.2019.00843\u003c/span\u003e\u003cspan address=\"10.3389/fendo.2019.00843\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. :843 2019;10:843.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStitt AW, Curtis TM, Chen M, Medina RJ, McKay GJ, Jenkins A, et al. The progress in understanding and treatment of diabetic retinopathy. Prog Retin Eye Res. 2016;51:156\u0026ndash;86. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.preteyeres.2015.08.001\u003c/span\u003e\u003cspan address=\"10.1016/j.preteyeres.2015.08.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGroup DRSR. Photocoagulation treatment of proliferative diabetic retinopathy: clinical application of Diabetic Retinopathy Study (DRS) findings, DRS Report Number 8. Ophthalmology. 1981;88(7):583\u0026ndash;600.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEsgin H, Samut HS. Topical ketorolac 0.5% for ocular pain relief during scatter laser photocoagulation with 532 nm green laser. J Ocul Pharmacol Ther. 2006;22(6):460\u0026ndash;4. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1089/jop.2006.22.460\u003c/span\u003e\u003cspan address=\"10.1089/jop.2006.22.460\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJohari M, Moallem M, Amini A, Sanie-Jahromi F. Pain Management Strategies before Pan-Retinal Photocoagulation for Diabetic Retinopathy: A Systematic Review. J Ophthalmol. 2024;2024(1):6662736. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1155/2024/6662736\u003c/span\u003e\u003cspan address=\"10.1155/2024/6662736\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCamu F, Vanlersberghe C. Pharmacology of systemic analgesics. Best Pract Res Clin Anaesthesiol. 2002;16(4):475\u0026ndash;88. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1053/bean.2002.0262\u003c/span\u003e\u003cspan address=\"10.1053/bean.2002.0262\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSingh RB, Khera T, Ly V, Saini C, Cho W, Shergill S, et al. Ocular complications of perioperative anesthesia: A review. Graefe\u0026rsquo;s Arch Clin Exp Ophthalmol. 2021;259:2069\u0026ndash;83. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s00417-021-05119-x\u003c/span\u003e\u003cspan address=\"10.1007/s00417-021-05119-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGroup DRSR. Indications for photocoagulation treatment of diabetic retinopathy: Diabetic Retinopathy Study Report 14. Int Ophthalmol Clin. 1987;27(4):239\u0026ndash;53. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/00004397-198702740-00004\u003c/span\u003e\u003cspan address=\"10.1097/00004397-198702740-00004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCrichton N. Visual analogue scale (VAS). J Clin Nurs. 2001;10(5):706. https://doi.org/.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRollman GB, Abdel-Shaheed J, Gillespie JM, Jones KS. Does past pain influence current pain: biological and psychosocial models of sex differences. Eur J Pain. 2004;8(5):427\u0026ndash;33. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ejpain.2004.03.002\u003c/span\u003e\u003cspan address=\"10.1016/j.ejpain.2004.03.002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBartley EJ, Fillingim RB. Sex differences in pain: a brief review of clinical and experimental findings. Br J Anaesth. 2013;111(1):52\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/bja/aet127\u003c/span\u003e\u003cspan address=\"10.1093/bja/aet127\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSanto AM, Del, Auge RM, Ferraz CA. Preemptive analgesia of metamizole versus ibuprofen in retinal laser photocoagulation. Rev Bras Oftalmol. 2016;75:14\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.5935/0034-7280.20160003\u003c/span\u003e\u003cspan address=\"10.5935/0034-7280.20160003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLautenbacher S, Peters JH, Heesen M, Scheel J, Kunz M. Age changes in pain perception: A systematic-review and meta-analysis of age effects on pain and tolerance thresholds. Neurosci Biobehav Rev. 2017;75:104\u0026ndash;13. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.neubiorev.2017.01.039\u003c/span\u003e\u003cspan address=\"10.1016/j.neubiorev.2017.01.039\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQueme LF, Ross JL, Jankowski MP. Peripheral mechanisms of ischemic myalgia. Front Cell Neurosci. 2017;11:419. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/fncel.2017.00419\u003c/span\u003e\u003cspan address=\"10.3389/fncel.2017.00419\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMolliver DC, Immke DC, Fierro L, Par\u0026eacute; M, Rice FL. ASIC3, an acid-sensing ion channel, is expressed in metaboreceptive sensory neurons. Mol Pain. 2005;1:35. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/1744-8069-1-35\u003c/span\u003e\u003cspan address=\"10.1186/1744-8069-1-35\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArendt-Nielsen L, Curatolo M, Drewes A. Human experimental pain models in drug development: translational pain research. Curr Opin Investig Drugs. 2007;8(1):41\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWeinberger D, Ron Y, Lichter H, Rosenblat I, Axer-Siegel R, Yassur Y. Analgesic effect of topical sodium diclofenac 0.1% drops during retinal laser photocoagulation. Br J Ophthalmol. 2000;84(2):135\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1136/bjo.84.2.135\u003c/span\u003e\u003cspan address=\"10.1136/bjo.84.2.135\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAziz A, Khan Z, Khan MA, Din SA, Chaudhari MZ. Topical sodium diclofenac during pan-retinal photocoagulation in patients with proliferative diabetic retinopathy. Pakistan J Med Heal Sci. 2022;16(1):1459\u0026ndash;62. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.53350/pjmhs221611459\u003c/span\u003e\u003cspan address=\"10.53350/pjmhs221611459\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZakrzewski PA, O\u0026rsquo;Donnell HL, Lam W-C. Oral versus topical diclofenac for pain prevention during panretinal photocoagulation. Ophthalmology. 2009;116(6):1168\u0026ndash;74. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ophtha.2009.01.022\u003c/span\u003e\u003cspan address=\"10.1016/j.ophtha.2009.01.022\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRamezani A, Entezari M, Shahbazi MM, Semnani Y, Nikkhah H, Yaseri M. Analgesic effect of topical sodium diclofenac before retinal photocoagulation for diabetic retinopathy: a randomized double-masked placebo-controlled intraindividual crossover clinical trial. Korean J Ophthalmol KJO. 2017;31(2):102. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3341/kjo.2017.31.2.102\u003c/span\u003e\u003cspan address=\"10.3341/kjo.2017.31.2.102\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChewa Raja JS, Singh S, Ismail F. Pre-emptive topical ketorolac tromethamine 0.5% for panretinal photocoagulation. J Ocul Pharmacol Ther. 2021;37(5):313\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1089/jop.2020.0089\u003c/span\u003e\u003cspan address=\"10.1089/jop.2020.0089\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCastro EF, de Okuda S, Amatto EA, Almeida VB, Gracia HG, Kara-Junior M. Preemptive analgesia of nepafenac 0.1% in retinal photocoagulation. Rev Bras Oftalmol. 2014;73:269\u0026ndash;72. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.5935/0034-7280.20140058\u003c/span\u003e\u003cspan address=\"10.5935/0034-7280.20140058\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePastore MR, De Giacinto C, Cirigliano G, D\u0026rsquo;Aloisio R, Addobbati R, Agostinis C, et al. Vitreous prostaglandin e2 changes after topical administration of diclofenac 0.1%, Indomethacin 0.5%, Nepafenac 0.3%, and Bromfenac 0.09%. Retina. 2020;40(9):1838\u0026ndash;45. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/IAE.0000000000002674\u003c/span\u003e\u003cspan address=\"10.1097/IAE.0000000000002674\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Non-steroidal anti-inflammatory drug, Diabetic Retinopathy, Topical analgesic, Eye Drops, Panretinal Photocoagulation","lastPublishedDoi":"10.21203/rs.3.rs-6790841/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6790841/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eTo investigate the effects of different topical non-steroidal anti-inflammatory drugs (NSAIDs) and demographic characteristics on pain perception associated with pan-retinal photocoagulation.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eBefore pan-retinal photocoagulation, patients received one of seven topical NSAIDs, while the control group received artificial tears. Following pan-retinal photocoagulation, subjective pain was assessed using the visual analog scale. The impact of demographic factors and NSAID type on visual analog scale scores was statistically analyzed. Demographic data were compared using the Mann-Whitney U test and NSAID groups with one-way ANOVA.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe study included 270 eyes from 270 patients. No significant differences were observed among NSAID groups regarding age, gender, diabetes duration, diabetic retinopathy type, number of intravitreal injections, pan-retinal photocoagulation sessions, or photocoagulation energy. In all participants, pain perception was higher in females (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), patients aged\u0026thinsp;\u0026le;\u0026thinsp;60 years (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and those with proliferative diabetic retinopathy (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Bromfenac (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), indomethacin (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), nepafenac 0.3% (P\u0026thinsp;=\u0026thinsp;0.002), and diclofenac (P\u0026thinsp;=\u0026thinsp;0.029) significantly reduced pain, whereas ketorolac trometamol, nepafenac 0.1%, and flurbiprofen did not. Among the effective NSAIDs, nepafenac 0.3% and diclofenac were ineffective in males, while diclofenac showed no efficacy in patients over 60 years of age or those with proliferative diabetic retinopathy. No NSAID demonstrated a significant effect in non-proliferative diabetic retinopathy patients.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eBromfenac and indomethacin demonstrate consistent analgesic efficacy in nearly all patients with pan-retinal photocoagulation-related pain, while nepafenac 0.3% and diclofenac are effective in a majority of cases. However, heightened pan-retinal photocoagulation-related pain in females, patients aged\u0026thinsp;\u0026le;\u0026thinsp;60 years and those with proliferative diabetic retinopathy may necessitate careful consideration in these populations.\u003c/p\u003e","manuscriptTitle":"Analgesic efficacy of 7 different topical NSAIDs in panretinal photocoagulation-associated pain","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-06 13:29:31","doi":"10.21203/rs.3.rs-6790841/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-28T08:25:42+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-26T16:33:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"271783504353581429139902649074950056055","date":"2025-07-21T11:30:58+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-18T10:58:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"256487588359144727459729712715962229573","date":"2025-06-04T16:15:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"151796397725662479515744671008840348817","date":"2025-06-04T11:27:21+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-04T10:02:20+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-06-04T07:04:49+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-03T03:31:07+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-03T03:28:24+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Ophthalmology","date":"2025-05-31T11:52:23+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c6e3c0ce-964a-4eff-9845-760a8c69597f","owner":[],"postedDate":"June 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-06T15:58:55+00:00","versionOfRecord":{"articleIdentity":"rs-6790841","link":"https://doi.org/10.1186/s12886-025-04376-2","journal":{"identity":"bmc-ophthalmology","isVorOnly":false,"title":"BMC Ophthalmology"},"publishedOn":"2025-10-02 15:56:56","publishedOnDateReadable":"October 2nd, 2025"},"versionCreatedAt":"2025-06-06 13:29:31","video":"","vorDoi":"10.1186/s12886-025-04376-2","vorDoiUrl":"https://doi.org/10.1186/s12886-025-04376-2","workflowStages":[]},"version":"v1","identity":"rs-6790841","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6790841","identity":"rs-6790841","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}