Topical dorzolamide as adjunctive treatment with intravitreal bevacizumab in bilateral diabetic macular edema

Topical dorzolamide as adjunctive treatment with intravitreal bevacizumab in bilateral diabetic macular edema | 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 Topical dorzolamide as adjunctive treatment with intravitreal bevacizumab in bilateral diabetic macular edema Ata Sadr, Meisam Sargazi, Shahram Banaie, Mahdi Asani, Seyedeh Sana Zamiri, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3182217/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract Background: Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is accepted as the gold standard treatment for center-involving diabetic macular edema (CI-DME). Adjunctive administration of topical dorzolamide may enhance the therapeutic effects of anti-VEGF agents. In this study, we compared the efficacy of topical dorzolamide plus intravitreal injection of bevacizumab (IVB) versus IVB alone in patients with bilateral DME. Methods: This randomized, double-blind, contralateral eye study included 50 eyes of 25 patients with bilateral DME. All eyes received three consecutive monthly injections of IVB. For each patient, one eye was randomized to instill dorzolamide eye drops three times a day as an intervention, and the other received artificial tear drops as a placebo. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) were evaluated before starting treatment and then monthly for the first 3 months. Results: Among 25 included patients, the average age was 56.64 ± 7.97 years, and 48% were female. BCVA did not improve significantly in any groups (P>0.05). No significant difference was observed in terms of BCVA between the intervention and control groups (P>0.05). The present study showed a decrease in CMT in both study groups (P<0.05). At month 3, the decrease in mean CMT from baseline was significantly higher in eyes receiving topical dorzolamide compared to the control group (-88.92 ± 82.90 vs -37.64 ± 86.16 µM, respectively; P = 0.037). IOP decreased significantly only in eyes receiving dorzolamide (P<0.001). Conclusions: The results of the present study indicate that adjunctive administration of topical dorzolamide has a beneficial effect on CMT reduction from baseline but it did not have an additive effect on BCVA improvement Compared to IVB monotherapy. dorzolamide macular edema bevacizumab Figures Figure 1 Figure 2 Figure 3 Introduction Diabetic macular edema (DME) is the major cause of preventable visual loss in the world (1). Various treatment modalities have been implemented to treat DME. Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents has been regarded as the gold standard treatment as the first option for center-involving DME (CI-DME) (2). However, in some cases of DME, the treatment with anti-VEGF agents tends to be unsatisfactory (3). Thus, the research for other treatment options goes on. Dorzolamide is a topical carbonic anhydrase inhibitor (CAI) that is primarily used in the treatment of glaucoma(4). Recent studies pointed out the effectiveness of dorzolamide in the treatment of macular edemas of various etiologies (5-10). However, the data concerning its efficacy in the treatment of DME is controversial (11-13). It was reported that adjuvant administration of topical timolol-dorzolamide with intravitreal bevacizumab (IVB) injection might be beneficial in reducing central macular thickness (CMT) (13). A more recent study reported that adjuvant administration of topical dorzolamide with IVB injection had no additive effects on the treatment of DME (12). Considering the conflicting results of previous studies on the effects of CAIs in the treatment of DME, as well as the uncertainty around the impact of the adjuvant use of topical dorzolamide on the efficacy of IVB injection, in the present study, we aimed to compare adjuvant administration of topical dorzolamide versus IVB monotherapy in diabetic macular edema. Material and Methods This prospective, randomized contralateral eye study was carried out in a tertiary referral ophthalmology center, Al-Zahra Eye Hospital, Zahedan, Iran between April 2021 and April 2022. A written informed consent was obtained from all participants. The study adhered to the tenets of the Declaration of Helsinki and was approved by Zahedan University of Medical Sciences Ethics Committee (identifier: IR.ZAUMS.REC.1400.305). The study was conducted on 50 eyes of 25 treatment-naive diabetic patients with bilateral CI-DME (CMT > 250 μm). The exclusion criteria were as follows: (1) history of any previous laser photocoagulation and/or intraocular surgery/injection; (2) pregnancy or breastfeeding; (3) non-center-involving DME (NCI-DME); (4) history of glaucoma; (5) presence of any other retinal diseases affecting the macula other than DME; (6) history of allergy to the CAIs; and (5) age below 18 years. Also, patients who failed to attend follow-up meetings or experienced unbearable side effects were excluded. All eyes were treated with three consecutive monthly intravitreal injection of 1.25 mg/0.05 mL bevacizumab (Avastin, Genentech Inc., San Francisco, CA, USA). All injections were performed in the operating room under sterile conditions. After applying topical tetracaine 0.5% (Anestocaine, Sina Darou, Tehran, Iran), the periocular skin and lid margins were wiped with povidone-iodine 10%. An eyelid speculum was then inserted and povidone-iodine 5% was applied to conjunctival sac for 3 minutes and then washed with sterile saline. Injections were performed using straight injection technique with a 30-gauge needle through the supratemporal quadrant of the eye approximately 3.5 to 4 mm posterior to the limbus. After injection, a sterile cotton swab was placed over the injection site to avoid reflux and subconjunctival hemorrhage. Then prophylactic topical antibiotics were prescribed. For each patient, one of the eyes was randomly allocated to receive topical dorzolamide (Dorzamid 2%, Sina Darou, Tehran, Iran) three times daily. An artificial tear drop (Tearlose, Sina darou, Tehran, Iran) was prescribed as a placebo for the contralateral eye. The drops' labels were removed to unify their shape, and the drops were coded with random three-digit numbers. Both patients and investigators were blinded to treatment groups. All eyes were assessed at baseline, one month, two months, and three months after the initiation of IVB treatment. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) were recorded at each appointment. CMT was measured using spectral-domain optical coherence tomography (SD-OCT; Spectralis, Heidelberg Engineering, Heidelberg, Germany). To facilitate statistical analysis, the decimal BCVA was converted to the logarithm of the minimum angle of resolution (logMAR) units. The IOP was measured with Goldmann applanation tonometry. The statistical analysis was performed using SPSS 23 (SPSS Inc., Chicago, IL). Quantitative data were described using mean and standard deviation, and qualitative data were described using frequency and percentage. Based on the normality status of quantitative variables independent sample t-test and repeated measures ANOVA were used for between-group and within-group analyses, respectively. A level of P< 0.05 was considered statistically significant. Results A total of 50 DME-affected eyes (25 people) were examined. Thirteen patients were male (52%), and 12 patients were female (48%). The mean age of participants was 56.64 ± 7.97. Table 1 presents CMT values at baseline and during follow-ups. Both groups showed a significant reduction in CMT during follow-ups (P0.05), the amplitude of the mean CMT reduction from baseline to month 3 was statistically greater in the intervention group compared with the control group (-88.92 ± 82.90 vs -37.64 ± 86.16 µM, respectively; P = 0.037). Table 1. CMT outcomes in study groups between-group P-value IVB + placebo Mean ± SD IVB + dorzolamide Mean ± SD 0.808 420.76 ± 148.91 430.52 ± 132.52 Baseline 0.673 412.52 ± 128.35 429.04 ± 145.80 1 st month 0.159 405.76 ± 126.42 362.76 ± 81.13 2 nd month 0.188 383.12 ± 128.62 341.60 ± 87.13 3 rd month P=0.047 P<0.001 within-group P-value 0.037 -37.64 ± 86.16 -88.92 ± 82.90 CMT Δ SD: standard deviation, Δ CMT: (CMT 3 rd month- CMT baseline) Table 2 illustrates BCVA values in the present study. BCVA did not change significantly in any treatment groups (P>0.05). No statistically significant difference in BCVA was identified between groups (P>0.05), and also there was no significant difference in BCVA improvement between study arms (P=0.758). Table 2. BCVA outcomes in study groups between-group P-value IVB + placebo Mean ± SD IVB + dorzolamide Mean ± SD 0.896 0.466 ± 0.283 0.478 ± 0.335 Baseline 0.771 0.443 ± 0.271 0.467 ± 0.305 1 st month 0.971 0.440 ± 0.287 0.437 ± 0.305 2 nd month 0.969 0.424 ± 0.290 0.427 ± 0.293 3 rd month 0.108 0.065 within-group P-value 0.758 -0.042 ± 0.734 -0.050 ± .112 BCVA Δ SD: standard deviation, Δ BCVA: (BCVA 3 rd month- BCVA baseline) Table 3 presents IOP results at baseline and on months 1, 2 and 3. Significant reduction in IOP was observed in the dorzolamide group (P<0.001). Although not significantly different at baseline (P=0.112), IOP was significantly lower in dorzolamide group at all appointments after initiating the treatment (P<0.001), and also there was a significant difference in IOP changes between the study groups (P<0.001). Table 3. IOP outcomes in study groups between-group P-value IVB + placebo Mean ± SD IVB + dorzolamide Mean ± SD 0.112 14.32 ± 1.573 15.04 ± 1.567 Baseline P<0.001 14.52 ± 1.558 12.56 ± 1.660 1 st month P<0.001 14.56 ± 1.557 12.32 ± 1.180 2 nd month P<0.001 14.32 ± 1.773 12.08 ± 1.115 3 rd month 0.559 P<0.001 within-group P-value P<0.001 0.00 ± 0.764 -2.96 ± 0.935 IOP Δ SD: standard deviation, Δ IOP: (IOP 3 rd month- IOP baseline) Discussions The present study investigated the effects of adjuvant topical dorzolamide in combination with IVB in treating DME. The results of this study demonstrate the significant positive role of dorzolamide administration as an adjunctive treatment in reducing CMT, but not in improving BCVA. It should be noted that the administration of dorzolamide caused a significant decrease in IOP compared to placebo. Several studies have pointed out the efficacy of topical dorzolamide in the treatment of cystoid macular edema (CME) (14). There are several theoretical frameworks regarding the effectiveness of dorzolamide in reducing macular edema. CAIs, including dorzolamide, might directly increase fluid transport across the RPE to improve macular edema by affecting RPE and Müller cells (14). Dorzolamide also seems to increase the blood flow in the choroid (15). In addition, CAIs cause acidification of the subretinal space, which may be effective in improving CME (16). Furthermore, there is evidence that the administration of dorzolamide might reduce the production of interleukin-6, an inflammatory cytokine (6). CAIs might also alter anti-VEGF clearance by their aqueous suppressant activity. Studies investigating the adjuvant administration of dorzolamide in combination with anti-VEGF reported positive therapeutic effects of dorzolamide in macular edema (8-10, 13). It was proposed that dorzolamide could be ineffective in treating DME due to difference in the pathophysiology of DME compared to other types of macular edema. It was founded that macular edemas caused by RPE dysfunction and outer retinal diseases are more easily treated with CAIs than those caused by blood vessel leakage and primary retinal vascular diseases (16, 17). Badawi et al. suggested that topical dorzolamide without IVB injection can be effective in CMT reduction and BCVA improvement (11). Three other studies have investigated the efficacy of topical aqueous suppressants combined with intravitreal anti-VEGF injection in treating DME (12, 13, 18). Fazel et al. showed that the adjuvant administration of topical dorzolamide was ineffective in improving the therapeutic effects of IVB injection (12). Mirshahi et al. reported a decrease in CMT and improvement in BCVA by adding timolol-dorzolamide eye drop to IVB injection (13). In 2022, a prospective cohort study indicated that adding topical dorzolamide–timolol as an adjuvant of intravitreal ranibizumab injection (IVR) has no statistically significant benefits (18). The limitations of this study were the short follow up and the small sample size. Conclusion Our study reveals that the addition of topical dorzolamide to IVB injection has statistically significant impact on reducing CMT but not on improving BCVA. It should be noted that the administration of dorzolamide was associated with a significant decrease in IOP compared to the placebo. Regarding inconsistent results, more extensive prospective trials with different drug combinations are necessary to evaluate the real effect of dorzolamide and other topical aqueous suppressants in the treatment of DME. Declarations Acknowledgment: The authors would like to express their gratitude to all the study participants for their cooperation. We would also like to thank Alzahra Eye Hospital Research Center, Zahedan University of Medical Sciences, Zahedan for their assistance in this manuscript. Ethics approval and consent to participate: Written informed consent was obtained from all patients, and the study protocol was approved by the institutional committee on human research (IR.ZAUMS.REC.1400.305), ensuring that it conformed to the ethical guidelines of the Declaration of Helsinki. Consent for publication: Not applicable Availability of data and materials: All data generated or analyzed during this study are included in this published article. Competing interests: The authors declare that they have no competing interests. Funding information: This study was supported by Alzahra Eye Hospital Research Center, Zahedan University of Medical Sciences, Zahedan. Authors' contributions Study concept and design: Ata Sadr, Alireza Maleki, Meisam Sargazi Acquisition of data: Ata Sadr, Mahdi Asani, Shahram Banaie Statistical analysis: Mehrad-Majd H, Drafting of the manuscript: Ata Sadr, Seyedeh Sana Zamiri, Hassan Mehrad-Majd, Seyed Omid Mohammadi Study supervision: Alireza Maleki References 1. Ixcamey M, Palma C. Diabetic macular edema. Disease-a-Month. 2021;67(5):101138. 2. Munk MR, Somfai GM, de Smet MD, Donati G, Menke MN, Garweg JG, et al. The role of intravitreal corticosteroids in the treatment of DME: predictive OCT biomarkers. International journal of molecular sciences. 2022;23(14):7585. 3. Rush RB, Rush SW. Faricimab for treatment-resistant diabetic macular edema. Clinical Ophthalmology. 2022:2797-801. 4. Aslam S, Gupta V. Carbonic anhydrase inhibitors. StatPearls [Internet]. 2022. 5. Genead MA, Mcanany JJ, Fishman GA. Topical dorzolamide for treatment of cystoid macular edema in patients with choroideremia. Retina (Philadelphia, Pa). 2012;32(4):826. 6. Suzuki T, Hayakawa K, Nakagawa Y, Onouchi H, Ogata M, Kawai K. Topical dorzolamide for macular edema in the early phase after vitrectomy and epiretinal membrane removal. Clinical Ophthalmology (Auckland, NZ). 2013;7:549. 7. Pacella E, Arrico L, Santamaria V, Turchetti P, Carbotti MR, La Torre G, et al. Dorzolamide chlorhydrate versus acetazolamide in the management of chronic macular edema in patients with retinitis pigmentosa: description of three case reports. Ophthalmology and eye Diseases. 2014;6:OED. S13617. 8. Obeid A, Hsu J, Ehmann D, Gao X, Sridhar J, Chiang A, et al. TOPICAL DORZOLAMIDE-TIMOLOL WITH INTRAVITREOUS ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR FOR RETINAL VEIN OCCLUSION: A PILOT STUDY. Retinal cases & brief reports. 2021;15(2):120-6. 9. Byeon SH, Kwon OW, Song JH, Kim SE, Park YS. Prolongation of activity of single intravitreal bevacizumab by adjuvant topical aqueous depressant (Timolol-Dorzolamide). Graefe's Archive for Clinical and Experimental Ophthalmology. 2009;247(1):35-42. 10. Sridhar J, Hsu J, Shahlaee A, Garg SJ, Spirn MJ, Fineman MS, et al. Topical dorzolamide-timolol with intravitreous anti–vascular endothelial growth factor for neovascular age-related macular degeneration. JAMA ophthalmology. 2016;134(4):437-43. 11. Badawi AE, Mokbel TH, Elhefney EM, Hagras SM, Abdelhameed AG. Efficacy of topical dorzolamide 2% in diabetic cystoid macular edema. International Journal of Ophthalmology. 2021;14(9):1413. 12. Fazel F, Nikpour H, Pourazizi M. Combination of intravitreal bevacizumab and topical dorzolamide versus intravitreal bevacizumab alone for diabetic macular edema: a randomized contralateral clinical trial. BioMed research international. 2020;2020. 13. Mirshahi A, Tadayoni R, Mohsenzadeh N, Rezvani TS, Abrishami M. Efficacy of adjuvant topical timolol–dorzolamide with intravitreal bevacizumab injection in diabetic macular edema: A contralateral eye study. Journal of Current Ophthalmology. 2019;31(2):168-71. 14. Shahsuvaryan ML. Carbonic anhydrase inhibitors in the management of macular edema: A review of the literature. Medical hypothesis discovery and innovation in ophthalmology. 2022;11(1):33-41. 15. Harris A, Ciulla T, Pratt L, Rechtman E, Kagemann L, Piper H, et al. The effects of dorzolamide on choroidal and retinal perfusion in non-exudative age related macular degeneration. British journal of ophthalmology. 2003;87(6):753-7. 16. Mack HG, Hassall M, Hall AJH, Simunovic MP, Fraser-Bell S, Ayton LN. 3.31 - Cystoid Macular Edema. In: Kenakin T, editor. Comprehensive Pharmacology. Oxford: Elsevier; 2022. p. 693-731. 17. Cox SN, Hay E, Bird AC. Treatment of chronic macular edema with acetazolamide. Archives of ophthalmology. 1988;106(9):1190-5. 18. Gadwal SM, Madbouly WA, Mansour MN. The Additive Effect of Topical Dorzolamide-Timolol with Intravitreal Ranibizumab Injection in Diabetic Macular Edema. Al-Azhar International Medical Journal. 2022;3(11):191-6. Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions 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-3182217","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":225596302,"identity":"d9c29eac-20ef-47c8-af91-3e9dd220fae7","order_by":0,"name":"Ata Sadr","email":"","orcid":"","institution":"Zahedan University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Ata","middleName":"","lastName":"Sadr","suffix":""},{"id":225596303,"identity":"15c13637-b957-4f7f-abe7-3665c9223064","order_by":1,"name":"Meisam Sargazi","email":"","orcid":"","institution":"Zahedan University of Medical 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world\u0026nbsp;(1). Various treatment modalities have been implemented to treat DME. Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents has been\u0026nbsp;regarded as the gold standard treatment\u0026nbsp;as the first option\u0026nbsp;for center-involving DME (CI-DME)\u0026nbsp;(2). However, in some cases of DME, the treatment with anti-VEGF agents tends to be unsatisfactory\u0026nbsp;(3). Thus, the research for other treatment options goes on.\u003c/p\u003e\n\u003cp\u003eDorzolamide is a topical carbonic anhydrase inhibitor (CAI) that is primarily used in the treatment of glaucoma(4). Recent studies pointed out the effectiveness of dorzolamide in the treatment of macular edemas of various etiologies\u0026nbsp;(5-10). However, the data concerning its efficacy in the treatment of DME is controversial\u0026nbsp;(11-13). It was reported that adjuvant administration of topical timolol-dorzolamide with intravitreal bevacizumab (IVB) injection might be beneficial in reducing central macular thickness (CMT)\u0026nbsp;(13). A more recent study reported that adjuvant administration of topical dorzolamide with IVB injection had no additive effects on the treatment of DME\u0026nbsp;(12).\u003c/p\u003e\n\u003cp\u003eConsidering the conflicting results of previous studies on the effects of CAIs in the treatment of DME, as well as the uncertainty around the impact of the adjuvant use of topical dorzolamide on the efficacy of IVB injection, in the present study, we aimed to compare adjuvant administration of topical dorzolamide versus IVB monotherapy in diabetic macular edema.\u003c/p\u003e"},{"header":"Material and Methods","content":"\u003cp\u003eThis prospective, randomized contralateral eye study was carried out in a tertiary referral ophthalmology center,\u0026nbsp;Al-Zahra Eye Hospital,\u0026nbsp;Zahedan, Iran\u0026nbsp;between April 2021 and April 2022.\u0026nbsp;A written informed consent was obtained from all participants. The study adhered to the tenets of the Declaration of Helsinki and was approved by\u0026nbsp;Zahedan University of Medical Sciences\u0026nbsp;Ethics Committee (identifier: IR.ZAUMS.REC.1400.305).\u003c/p\u003e\n\u003cp\u003eThe study was conducted on 50 eyes of 25 treatment-naive diabetic patients with bilateral CI-DME (CMT \u0026gt; 250 \u0026mu;m). The exclusion criteria were as follows: (1) history of any previous laser photocoagulation and/or intraocular surgery/injection; (2) pregnancy or breastfeeding; (3) non-center-involving DME (NCI-DME); (4) history of glaucoma; (5) presence of any other retinal diseases affecting the macula other than DME; (6) history of allergy to the CAIs; and (5) age below 18 years. Also, patients who failed to attend follow-up meetings or experienced unbearable side effects were excluded.\u003c/p\u003e\n\u003cp\u003eAll eyes were treated with three consecutive monthly intravitreal injection of 1.25 mg/0.05 mL bevacizumab\u0026nbsp;(Avastin, Genentech Inc., San Francisco, CA, USA). All injections were performed in the operating room under sterile conditions. After applying topical tetracaine 0.5% (Anestocaine, Sina Darou, Tehran, Iran), the periocular skin and lid margins were wiped with povidone-iodine 10%. An eyelid speculum was then inserted and povidone-iodine 5% was applied to conjunctival sac for 3 minutes and then washed with sterile saline. Injections were performed using straight injection technique with a 30-gauge needle through the supratemporal quadrant of the eye approximately 3.5 to 4 mm posterior to the limbus. After injection, a sterile cotton swab was placed over the injection site to avoid reflux and subconjunctival hemorrhage. Then prophylactic topical antibiotics were prescribed.\u003c/p\u003e\n\u003cp\u003eFor each patient, one of the eyes was randomly allocated to receive topical dorzolamide (Dorzamid 2%, Sina Darou, Tehran, Iran) three times daily. An artificial tear drop\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e(Tearlose, Sina darou, Tehran, Iran) was prescribed as a placebo for the contralateral eye. The drops\u0026apos; labels were removed to unify their shape, and the drops were coded with random three-digit numbers. Both patients and investigators were blinded to treatment groups.\u003c/p\u003e\n\u003cp\u003eAll eyes were assessed at baseline, one month, two months, and three months after the initiation of IVB treatment. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) were recorded at each appointment. CMT was measured using spectral-domain optical coherence tomography (SD-OCT; Spectralis, Heidelberg Engineering, Heidelberg, Germany). To facilitate statistical analysis, the decimal BCVA was converted to the logarithm of the minimum angle of resolution (logMAR) units. The IOP was measured with Goldmann applanation tonometry.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe statistical analysis was performed using SPSS 23 (SPSS Inc., Chicago, IL). Quantitative data were described using mean and standard deviation, and qualitative data were described using frequency and percentage. Based on the normality status of quantitative variables independent sample t-test and repeated measures ANOVA were used for between-group and within-group analyses, respectively. A level of P\u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 50 DME-affected eyes (25 people) were examined. Thirteen patients were male (52%), and 12 patients were female (48%). The mean age of participants was 56.64 \u0026plusmn; 7.97.\u003c/p\u003e\n\u003cp\u003eTable 1 presents CMT values at baseline and during follow-ups. Both groups showed a significant reduction in CMT during follow-ups (P\u0026lt;0.05). Although there was no significant difference in CMT between the groups at any time after the initiation of treatment (P\u0026gt;0.05), the amplitude of the mean CMT reduction from baseline to month 3 was statistically greater in the intervention group compared with the control group (-88.92 \u0026plusmn; 82.90 vs -37.64 \u0026plusmn; 86.16 \u0026micro;M, respectively; P = 0.037).\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cdiv align=\"center\" style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;'\u003e\n \u003ctable dir=\"rtl\" style=\"border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 437.55pt;border-width: medium medium 1pt;border-style: none none solid;border-color: currentcolor currentcolor white;border-image: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan style='font-size:16px;line-height: 115%;font-family:\"Times New Roman\",serif;'\u003eTable 1. CMT outcomes in study groups\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:130.5pt;border:solid white 1.0pt;border-top:none;background:#D9D9D9;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003ebetween-group \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; P-value\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:95.7pt;border-top:none;border-left:solid white 1.0pt;border-bottom:solid white 1.0pt;border-right:none;background:#D9D9D9;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eIVB + \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;placebo\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eMean \u0026plusmn; SD\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:93.3pt;border-top:none;border-left:solid white 1.0pt;border-bottom:solid white 1.0pt;border-right:none;background:#D9D9D9;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eIVB + dorzolamide\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eMean \u0026plusmn; SD\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118.05pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 130.5pt;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor white white;border-image: none;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Century\",serif;color:black;'\u003e0.808\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95.7pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e420.76 \u0026plusmn; 148.91\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93.3pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:right;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e430.52\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family: \"Times New Roman\",serif;color:black;'\u003e\u0026plusmn;\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e132.52\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118.05pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eBaseline\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:130.5pt;border:solid white 1.0pt;border-top:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Century\",serif;color:black;'\u003e0.673\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95.7pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e412.52\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family: \"Times New Roman\",serif;color:black;'\u003e\u0026plusmn;\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e128.35\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93.3pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e429.04\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family: \"Times New Roman\",serif;color:black;'\u003e\u0026plusmn;\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e145.80\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118.05pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e1\u003csup\u003est\u003c/sup\u003e month\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:130.5pt;border:solid white 1.0pt;border-top:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Century\",serif;color:black;'\u003e0.159\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95.7pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e405.76\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family: \"Times New Roman\",serif;color:black;'\u003e\u0026plusmn;\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e126.42\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93.3pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e362.76\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family: \"Times New Roman\",serif;color:black;'\u003e\u0026plusmn;\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e81.13\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118.05pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e2\u003csup\u003end\u003c/sup\u003e month\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:130.5pt;border:solid white 1.0pt;border-top:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Century\",serif;color:black;'\u003e0.188\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95.7pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e383.12\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family: \"Times New Roman\",serif;color:black;'\u003e\u0026plusmn;\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e128.62\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93.3pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e341.60\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family: \"Times New Roman\",serif;color:black;'\u003e\u0026plusmn;\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e87.13\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118.05pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e3\u003csup\u003erd\u003c/sup\u003e month\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:130.5pt;border:solid white 1.0pt;border-top:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Century\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:95.7pt;border-top:none;border-left:solid white 1.0pt;border-bottom:solid white 1.0pt;border-right:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eP=0.047\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:93.3pt;border-top:none;border-left:solid white 1.0pt;border-bottom:solid white 1.0pt;border-right:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eP\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118.05pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003ewithin-group \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; P-value\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:130.5pt;border:solid white 1.0pt;border-top:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Century\",serif;color:black;'\u003e0.037\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:95.7pt;border-top:none;border-left:solid white 1.0pt;border-bottom:solid white 1.0pt;border-right:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e-37.64 \u0026plusmn; 86.16\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:93.3pt;border-top:none;border-left:solid white 1.0pt;border-bottom:solid white 1.0pt;border-right:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e-88.92\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family: \"Times New Roman\",serif;color:black;'\u003e\u0026plusmn; 82.90\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118.05pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eCMT\u003c/span\u003e\u003cspan style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e\u0026Delta;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width:437.55pt;border:solid white 1.0pt;border-top:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"LTR\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;line-height:115%;'\u003e\u003cspan style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eSD: standard deviation, \u003cspan dir=\"RTL\"\u003e\u0026Delta;\u003c/span\u003eCMT: (CMT\u0026nbsp;\u003c/span\u003e\u003cspan style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e3\u003csup\u003erd\u003c/sup\u003e month-\u003c/span\u003e\u003cspan style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e\u0026nbsp;CMT\u003c/span\u003e\u003cspan style='font-size:16px;line-height: 115%;font-family:\"Times New Roman\",serif;color:black;'\u003e\u0026nbsp;baseline)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;line-height:normal;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eTable 2 illustrates BCVA values in the present study. BCVA did not change significantly in any treatment groups (P\u0026gt;0.05). No statistically significant difference in BCVA was identified between groups (P\u0026gt;0.05), and also there was no significant difference in BCVA improvement between study arms (P=0.758).\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cdiv align=\"center\" style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;'\u003e\n \u003ctable dir=\"rtl\" style=\"border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 437.55pt;border-width: medium medium 1pt;border-style: none none solid;border-color: currentcolor currentcolor white;border-image: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan style='font-size:16px;line-height: 115%;font-family:\"Times New Roman\",serif;'\u003eTable 2. BCVA outcomes in study groups\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:130.5pt;border:solid white 1.0pt;border-top:none;background:#D9D9D9;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003ebetween-group \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; P-value\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:95.7pt;border-top:none;border-left:solid white 1.0pt;border-bottom:solid white 1.0pt;border-right:none;background:#D9D9D9;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eIVB + \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;placebo\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eMean \u0026plusmn; SD\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:93.3pt;border-top:none;border-left:solid white 1.0pt;border-bottom:solid white 1.0pt;border-right:none;background:#D9D9D9;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eIVB + dorzolamide\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eMean \u0026plusmn; SD\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118.05pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 130.5pt;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor white white;border-image: none;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Century\",serif;color:black;'\u003e0.896\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95.7pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e0.466 \u0026plusmn; 0.283\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93.3pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e0.478\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height: 115%;font-family:\"Times New Roman\",serif;color:black;'\u003e\u0026plusmn;\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e0.335\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118.05pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eBaseline\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:130.5pt;border:solid white 1.0pt;border-top:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Century\",serif;color:black;'\u003e0.771\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95.7pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e0.443\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family: \"Times New Roman\",serif;color:black;'\u003e\u0026plusmn;\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e0.271\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93.3pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e0.467\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family: \"Times New Roman\",serif;color:black;'\u003e\u0026plusmn;\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e0.305\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118.05pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e1\u003csup\u003est\u003c/sup\u003e month\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:130.5pt;border:solid white 1.0pt;border-top:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Century\",serif;color:black;'\u003e0.971\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95.7pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e0.440\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family: \"Times New Roman\",serif;color:black;'\u003e\u0026plusmn;\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e0.287\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93.3pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e0.437\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family: \"Times New Roman\",serif;color:black;'\u003e\u0026plusmn;\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e0.305\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118.05pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e2\u003csup\u003end\u003c/sup\u003e month\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:130.5pt;border:solid white 1.0pt;border-top:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Century\",serif;color:black;'\u003e0.969\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95.7pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e0.424\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family: \"Times New Roman\",serif;color:black;'\u003e\u0026plusmn;\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e0.290\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93.3pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e0.427\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family: \"Times New Roman\",serif;color:black;'\u003e\u0026plusmn;\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e0.293\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118.05pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e3\u003csup\u003erd\u003c/sup\u003e month\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:130.5pt;border:solid white 1.0pt;border-top:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Century\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:95.7pt;border-top:none;border-left:solid white 1.0pt;border-bottom:solid white 1.0pt;border-right:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e0.108\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:93.3pt;border-top:none;border-left:solid white 1.0pt;border-bottom:solid white 1.0pt;border-right:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e0.065\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118.05pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003ewithin-group \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; P-value\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:130.5pt;border:solid white 1.0pt;border-top:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Century\",serif;color:black;'\u003e0.758\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:95.7pt;border-top:none;border-left:solid white 1.0pt;border-bottom:solid white 1.0pt;border-right:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e-0.042\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family: \"Times New Roman\",serif;color:black;'\u003e\u0026plusmn; 0.734\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:93.3pt;border-top:none;border-left:solid white 1.0pt;border-bottom:solid white 1.0pt;border-right:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e-0.050\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family: \"Times New Roman\",serif;color:black;'\u003e\u0026plusmn;\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e.112\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118.05pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eBCVA\u003c/span\u003e\u003cspan style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e\u0026Delta;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width:437.55pt;border:solid white 1.0pt;border-top:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"LTR\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;line-height:115%;'\u003e\u003cspan style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eSD: standard deviation, \u003cspan dir=\"RTL\"\u003e\u0026Delta;\u003c/span\u003eBCVA: (BCVA\u0026nbsp;\u003c/span\u003e\u003cspan style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e3\u003csup\u003erd\u003c/sup\u003e month-\u003c/span\u003e\u003cspan style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e\u0026nbsp;BCVA\u003c/span\u003e\u003cspan style='font-size:16px;line-height: 115%;font-family:\"Times New Roman\",serif;color:black;'\u003e\u0026nbsp;baseline)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;line-height:20.0pt;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eTable 3 presents IOP results at baseline and on months 1, 2 and 3. Significant reduction in IOP was observed in the dorzolamide group (P\u0026lt;0.001). Although not significantly different at baseline (P=0.112), IOP was significantly lower in dorzolamide group at all appointments after initiating the treatment (P\u0026lt;0.001), and also there was a significant difference in IOP changes between the study groups (P\u0026lt;0.001).\u003c/p\u003e\n\u003cdiv align=\"center\" style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;'\u003e\n \u003ctable dir=\"rtl\" style=\"border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 437.55pt;border-width: medium medium 1pt;border-style: none none solid;border-color: currentcolor currentcolor white;border-image: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"LTR\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan style='font-size:16px;line-height: 115%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan style='font-size:16px;line-height: 115%;font-family:\"Times New Roman\",serif;'\u003eTable 3. IOP outcomes in study groups\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:130.5pt;border:solid white 1.0pt;border-top:none;background:#D9D9D9;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003ebetween-group \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; P-value\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:95.7pt;border-top:none;border-left:solid white 1.0pt;border-bottom:solid white 1.0pt;border-right:none;background:#D9D9D9;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eIVB + \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;placebo\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eMean \u0026plusmn; SD\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:93.3pt;border-top:none;border-left:solid white 1.0pt;border-bottom:solid white 1.0pt;border-right:none;background:#D9D9D9;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eIVB + dorzolamide\u003c/span\u003e\u003c/p\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eMean \u0026plusmn; SD\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118.05pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 130.5pt;border-width: medium 1pt 1pt;border-style: none solid solid;border-color: currentcolor white white;border-image: none;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Century\",serif;color:black;'\u003e0.112\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95.7pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e14.32 \u0026plusmn; 1.573\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93.3pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e15.04\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height: 115%;font-family:\"Times New Roman\",serif;color:black;'\u003e\u0026plusmn;\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e1.567\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118.05pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eBaseline\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:130.5pt;border:solid white 1.0pt;border-top:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Century\",serif;color:black;'\u003eP\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95.7pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e14.52\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family: \"Times New Roman\",serif;color:black;'\u003e\u0026plusmn;\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e1.558\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93.3pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e12.56\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family: \"Times New Roman\",serif;color:black;'\u003e\u0026plusmn;\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e1.660\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118.05pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e1\u003csup\u003est\u003c/sup\u003e month\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:130.5pt;border:solid white 1.0pt;border-top:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Century\",serif;color:black;'\u003eP\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95.7pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e14.56\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family: \"Times New Roman\",serif;color:black;'\u003e\u0026plusmn;\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e1.557\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93.3pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e12.32\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family: \"Times New Roman\",serif;color:black;'\u003e\u0026plusmn;\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e1.180\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118.05pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e2\u003csup\u003end\u003c/sup\u003e month\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:130.5pt;border:solid white 1.0pt;border-top:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Century\",serif;color:black;'\u003eP\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95.7pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e14.32\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family: \"Times New Roman\",serif;color:black;'\u003e\u0026plusmn;\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e1.773\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93.3pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(242, 242, 242);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e12.08\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family: \"Times New Roman\",serif;color:black;'\u003e\u0026plusmn;\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e1.115\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118.05pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e3\u003csup\u003erd\u003c/sup\u003e month\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:130.5pt;border:solid white 1.0pt;border-top:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Century\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:95.7pt;border-top:none;border-left:solid white 1.0pt;border-bottom:solid white 1.0pt;border-right:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e0.559\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:93.3pt;border-top:none;border-left:solid white 1.0pt;border-bottom:solid white 1.0pt;border-right:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eP\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118.05pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003ewithin-group \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; P-value\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:130.5pt;border:solid white 1.0pt;border-top:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eP\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:95.7pt;border-top:none;border-left:solid white 1.0pt;border-bottom:solid white 1.0pt;border-right:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e0.00\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family: \"Times New Roman\",serif;color:black;'\u003e\u0026plusmn; 0.764\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:93.3pt;border-top:none;border-left:solid white 1.0pt;border-bottom:solid white 1.0pt;border-right:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e-2.96\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family: \"Times New Roman\",serif;color:black;'\u003e\u0026plusmn; 0.935\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118.05pt;border-width: medium medium 1pt 1pt;border-style: none none solid solid;border-color: currentcolor currentcolor white white;background: rgb(217, 217, 217);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp dir=\"RTL\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;text-align:center;line-height:115%;'\u003e\u003cspan dir=\"LTR\" style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eIOP\u003c/span\u003e\u003cspan style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e\u0026Delta;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width:437.55pt;border:solid white 1.0pt;border-top:none;background:#F2F2F2;padding:0in 5.4pt 0in 5.4pt;height:16.15pt;\"\u003e\n \u003cp dir=\"LTR\" style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;line-height:115%;'\u003e\u003cspan style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003eSD: standard deviation, \u003cspan dir=\"RTL\"\u003e\u0026Delta;\u003c/span\u003eIOP: (IOP\u0026nbsp;\u003c/span\u003e\u003cspan style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e3\u003csup\u003erd\u003c/sup\u003e month-\u003c/span\u003e\u003cspan style='font-size:16px;line-height:115%;font-family:\"Times New Roman\",serif;color:black;'\u003e\u0026nbsp;IOP\u003c/span\u003e\u003cspan style='font-size:16px;line-height: 115%;font-family:\"Times New Roman\",serif;color:black;'\u003e\u0026nbsp;baseline)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;font-size:11.0pt;font-family:\"Calibri\",sans-serif;line-height:normal;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e"},{"header":"Discussions","content":"\u003cp\u003eThe present study investigated the effects of adjuvant topical dorzolamide in combination with IVB in treating DME. The results of this study demonstrate the significant positive role of dorzolamide administration as an adjunctive treatment in reducing CMT, but not in improving BCVA. It should be noted that the administration of dorzolamide caused a significant decrease in IOP compared to placebo.\u003c/p\u003e\n\u003cp\u003eSeveral studies have pointed out the efficacy of topical dorzolamide in the treatment of cystoid macular edema (CME)\u0026nbsp;(14). There are several theoretical frameworks regarding the effectiveness of dorzolamide in reducing macular edema. CAIs, including dorzolamide, might directly increase fluid transport across the RPE to improve macular edema by affecting RPE and M\u0026uuml;ller cells\u0026nbsp;(14). Dorzolamide also seems to increase the blood flow in the choroid\u0026nbsp;(15). In addition, CAIs cause acidification of the subretinal space, which may be effective in improving CME\u0026nbsp;(16). Furthermore, there is evidence that the administration of dorzolamide might reduce the production of interleukin-6, an inflammatory cytokine\u0026nbsp;(6).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCAIs might also alter anti-VEGF clearance by their aqueous suppressant activity. Studies investigating the adjuvant administration of dorzolamide in combination with anti-VEGF reported positive therapeutic effects of dorzolamide in macular edema\u0026nbsp;(8-10, 13). It was proposed that dorzolamide could be ineffective in treating DME due to difference in the pathophysiology of DME compared to other types of macular edema. It was founded that macular edemas caused by RPE dysfunction and outer retinal diseases are more easily treated with CAIs than those caused by blood vessel leakage and primary retinal vascular diseases\u0026nbsp;(16, 17).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBadawi et al. suggested that topical dorzolamide without IVB injection can be effective in CMT reduction and BCVA improvement\u0026nbsp;(11). Three other studies have investigated the efficacy of topical aqueous suppressants combined with intravitreal anti-VEGF injection in treating DME\u0026nbsp;(12, 13, 18). Fazel et al. showed that the adjuvant administration of topical dorzolamide was ineffective in improving the therapeutic effects of IVB injection\u0026nbsp;(12). Mirshahi et al. reported a decrease in CMT and improvement in BCVA by adding timolol-dorzolamide eye drop to IVB injection\u0026nbsp;(13). In 2022, a prospective cohort study indicated that adding topical dorzolamide\u0026ndash;timolol as an adjuvant of intravitreal ranibizumab injection (IVR) has no statistically significant benefits\u0026nbsp;(18).\u003c/p\u003e\n\u003cp\u003eThe limitations of this study were the short follow up and the small sample size.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur study reveals that the addition of topical dorzolamide to IVB injection has statistically significant impact on reducing CMT but not on improving BCVA. It should be noted that the administration of dorzolamide was associated with a significant decrease in IOP compared to the placebo. Regarding inconsistent results, more extensive prospective trials with different drug combinations are necessary to evaluate the real effect of dorzolamide and other topical aqueous suppressants in the treatment of DME.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgment:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe authors would like to express their gratitude to all the study participants for their cooperation. We would also like to thank Alzahra Eye Hospital Research Center, Zahedan University of Medical Sciences, Zahedan for their assistance in this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from all patients, and the study protocol was approved by the institutional committee on human research (IR.ZAUMS.REC.1400.305), ensuring that it conformed to the ethical guidelines of the Declaration of Helsinki.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eAll data generated or analyzed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no competing\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003einterests.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding information:\u003c/strong\u003e This study was supported by Alzahra Eye Hospital Research Center, Zahedan University of Medical Sciences, Zahedan.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy concept and design: Ata Sadr, Alireza Maleki, Meisam Sargazi\u003c/p\u003e\n\u003cp\u003eAcquisition of data: Ata Sadr, Mahdi Asani, Shahram Banaie\u003c/p\u003e\n\u003cp\u003eStatistical analysis: Mehrad-Majd H,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDrafting of the manuscript: Ata Sadr, Seyedeh Sana Zamiri, Hassan Mehrad-Majd, Seyed Omid Mohammadi\u003c/p\u003e\n\u003cp\u003eStudy supervision: Alireza Maleki\u003c/p\u003e"},{"header":"References","content":"\u003cp\u003e1.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Ixcamey M, Palma C. Diabetic macular edema. Disease-a-Month. 2021;67(5):101138.\u003c/p\u003e\n\u003cp\u003e2.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Munk MR, Somfai GM, de Smet MD, Donati G, Menke MN, Garweg JG, et al. The role of intravitreal corticosteroids in the treatment of DME: predictive OCT biomarkers. International journal of molecular sciences. 2022;23(14):7585.\u003c/p\u003e\n\u003cp\u003e3.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Rush RB, Rush SW. Faricimab for treatment-resistant diabetic macular edema. Clinical Ophthalmology. 2022:2797-801.\u003c/p\u003e\n\u003cp\u003e4.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Aslam S, Gupta V. Carbonic anhydrase inhibitors. StatPearls [Internet]. 2022.\u003c/p\u003e\n\u003cp\u003e5.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Genead MA, Mcanany JJ, Fishman GA. Topical dorzolamide for treatment of cystoid macular edema in patients with choroideremia. Retina (Philadelphia, Pa). 2012;32(4):826.\u003c/p\u003e\n\u003cp\u003e6.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Suzuki T, Hayakawa K, Nakagawa Y, Onouchi H, Ogata M, Kawai K. Topical dorzolamide for macular edema in the early phase after vitrectomy and epiretinal membrane removal. Clinical Ophthalmology (Auckland, NZ). 2013;7:549.\u003c/p\u003e\n\u003cp\u003e7.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Pacella E, Arrico L, Santamaria V, Turchetti P, Carbotti MR, La Torre G, et al. Dorzolamide chlorhydrate versus acetazolamide in the management of chronic macular edema in patients with retinitis pigmentosa: description of three case reports. Ophthalmology and eye Diseases. 2014;6:OED. S13617.\u003c/p\u003e\n\u003cp\u003e8.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Obeid A, Hsu J, Ehmann D, Gao X, Sridhar J, Chiang A, et al. TOPICAL DORZOLAMIDE-TIMOLOL WITH INTRAVITREOUS ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR FOR RETINAL VEIN OCCLUSION: A PILOT STUDY. Retinal cases \u0026amp; brief reports. 2021;15(2):120-6.\u003c/p\u003e\n\u003cp\u003e9.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Byeon SH, Kwon OW, Song JH, Kim SE, Park YS. Prolongation of activity of single intravitreal bevacizumab by adjuvant topical aqueous depressant (Timolol-Dorzolamide). Graefe\u0026apos;s Archive for Clinical and Experimental Ophthalmology. 2009;247(1):35-42.\u003c/p\u003e\n\u003cp\u003e10.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Sridhar J, Hsu J, Shahlaee A, Garg SJ, Spirn MJ, Fineman MS, et al. Topical dorzolamide-timolol with intravitreous anti\u0026ndash;vascular endothelial growth factor for neovascular age-related macular degeneration. JAMA ophthalmology. 2016;134(4):437-43.\u003c/p\u003e\n\u003cp\u003e11.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Badawi AE, Mokbel TH, Elhefney EM, Hagras SM, Abdelhameed AG. Efficacy of topical dorzolamide 2% in diabetic cystoid macular edema. International Journal of Ophthalmology. 2021;14(9):1413.\u003c/p\u003e\n\u003cp\u003e12.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Fazel F, Nikpour H, Pourazizi M. Combination of intravitreal bevacizumab and topical dorzolamide versus intravitreal bevacizumab alone for diabetic macular edema: a randomized contralateral clinical trial. BioMed research international. 2020;2020.\u003c/p\u003e\n\u003cp\u003e13.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Mirshahi A, Tadayoni R, Mohsenzadeh N, Rezvani TS, Abrishami M. Efficacy of adjuvant topical timolol\u0026ndash;dorzolamide with intravitreal bevacizumab injection in diabetic macular edema: A contralateral eye study. Journal of Current Ophthalmology. 2019;31(2):168-71.\u003c/p\u003e\n\u003cp\u003e14.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Shahsuvaryan ML. Carbonic anhydrase inhibitors in the management of macular edema: A review of the literature. Medical hypothesis discovery and innovation in ophthalmology. 2022;11(1):33-41.\u003c/p\u003e\n\u003cp\u003e15.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Harris A, Ciulla T, Pratt L, Rechtman E, Kagemann L, Piper H, et al. The effects of dorzolamide on choroidal and retinal perfusion in non-exudative age related macular degeneration. British journal of ophthalmology. 2003;87(6):753-7.\u003c/p\u003e\n\u003cp\u003e16.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Mack HG, Hassall M, Hall AJH, Simunovic MP, Fraser-Bell S, Ayton LN. 3.31 - Cystoid Macular Edema. In: Kenakin T, editor. Comprehensive Pharmacology. Oxford: Elsevier; 2022. p. 693-731.\u003c/p\u003e\n\u003cp\u003e17.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Cox SN, Hay E, Bird AC. Treatment of chronic macular edema with acetazolamide. Archives of ophthalmology. 1988;106(9):1190-5.\u003c/p\u003e\n\u003cp\u003e18. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Gadwal SM, Madbouly WA, Mansour MN. The Additive Effect of Topical Dorzolamide-Timolol with Intravitreal Ranibizumab Injection in Diabetic Macular Edema. Al-Azhar International Medical Journal. 2022;3(11):191-6.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"dorzolamide, macular edema, bevacizumab","lastPublishedDoi":"10.21203/rs.3.rs-3182217/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3182217/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIntravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is accepted as the gold standard treatment for center-involving diabetic macular edema (CI-DME). Adjunctive administration of topical dorzolamide may enhance the therapeutic effects of anti-VEGF agents. In this study, we compared the efficacy of topical dorzolamide plus intravitreal injection of bevacizumab (IVB) versus IVB alone in patients with bilateral DME.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis randomized, double-blind, contralateral eye study included 50 eyes of 25 patients with bilateral DME. All eyes received three consecutive monthly injections of IVB. For each patient, one eye was randomized to instill dorzolamide eye drops three times a day as an intervention, and the other received artificial tear drops as a placebo. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) were evaluated before starting treatment and then monthly for the first 3 months.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong 25 included patients, the average age was 56.64 ± 7.97 years, and 48% were female. BCVA did not improve significantly in any groups (P\u0026gt;0.05). No significant difference was observed in terms of BCVA between the intervention and control groups (P\u0026gt;0.05). The present study showed a decrease in CMT in both study groups (P\u0026lt;0.05). At month 3, the decrease in mean CMT from baseline was significantly higher in eyes receiving topical dorzolamide compared to the control group (-88.92 ± 82.90 vs -37.64 ± 86.16 µM, respectively; P = 0.037). IOP decreased significantly only in eyes receiving dorzolamide (P\u0026lt;0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe results of the present study indicate that adjunctive administration of topical dorzolamide has a beneficial effect on CMT reduction from baseline but it did not have an additive effect on BCVA improvement Compared to IVB monotherapy.\u003c/p\u003e","manuscriptTitle":"Topical dorzolamide as adjunctive treatment with intravitreal bevacizumab in bilateral diabetic macular edema","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2024-01-17 21:20:06","doi":"10.21203/rs.3.rs-3182217/v2","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2023-08-10 19:49:13","doi":"10.21203/rs.3.rs-3182217/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"245a715f-45ed-460e-bdc2-fb329e56d40f","owner":[],"postedDate":"January 17th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-11-28T05:32:43+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-17 21:20:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v2","identity":"rs-3182217","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3182217","identity":"rs-3182217","version":["v2"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}