Occurrence and Advancement of Diabetic Retinopathy in a Tertiary Care Setting: A Preliminary Report with Initial Overview and Recommended Protocols for Subsequent Screening

Occurrence and Advancement of Diabetic Retinopathy in a Tertiary Care Setting: A Preliminary Report with Initial Overview and Recommended Protocols for Subsequent Screening | 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 Occurrence and Advancement of Diabetic Retinopathy in a Tertiary Care Setting: A Preliminary Report with Initial Overview and Recommended Protocols for Subsequent Screening P. Salim Mahar, Mohammad Daniyal Monis, M. Fahadullah Khan, Shahid Ahsan, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4452499/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background/Aims The objective of this study is to evaluate diabetic patients with either a normal fundus or non-proliferative diabetic retinopathy (NPDR) changes, examining retinal alterations during follow-up, and proposing follow-up guidelines within a tertiary eye care setting. Methods A 5-year prospective longitudinal study is being conducted at the Diabetic Clinic of Al Ibrahim Eye Hospital/Isra Postgraduate Institute of Ophthalmology, Karachi. Induction for the research took place from October 2021 to March 2022, and a 2-year preliminary report is presented here. Newly diagnosed type II diabetic patients with normal fundus or NPDR of any stage, irrespective of age, gender, or glycemic status, who were willing to participate and agreed to follow-ups, were included. Patients with proliferative diabetic retinopathy (PDR), diabetic macular edema (DME), fundus non-visibility, or systemic complications of diabetes were excluded. Results A total of 251 patients were enrolled, consisting of 80 individuals with a normal fundus and 171 with different stages of NPDR, including mild (n = 59), moderate (n = 91), and severe (n = 21) retinopathy. The incidence of progression from mild to moderate NPDR was noted to be 52.5%, with a median time of 3.5 months. Progression from moderate to severe NPDR occurred in 37.1% of cases, with a median time of 4.5 months. Similarly, DME developed in 5% of patients with mild NPDR over 8 months, in 22.2% with moderate NPDR over 7 months, and in 37.5% with severe NPDR over 4.4 months. Conclusion This study suggests that the incidence and progression of NPDR stages, along with the development of DME, may occur in a shorter duration in diabetic patients compared to what is suggested in existing literature. Diabetes Mellitus Diabetic Macular Edema Non-Proliferative Diabetic Retinopathy Proliferative Diabetic Retinopathy Vision Screening Figures Figure 1 Introduction Pakistan currently ranks third in the world for diabetes prevalence, trailing only China and India. With nearly 33 million individuals affected, this number is projected to soar to 629 million globally by 2045 [ 1 , 2 ]. Approximately one in three adults in Pakistan is estimated to have diabetes, with many being diagnosed with type 2 diabetes during their working years, while others are diagnosed only after complications arise. As the prevalence of diabetes continues to escalate exponentially, the incidence of diabetic eye complications is expected to follow suit. Diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) stand out as the most common causes of diabetes-related vision loss. DME arises from vessel leakage leading to edema, while proliferative diabetic retinopathy results from retinal ischemia fostering neovascularization and culminating in vitreous hemorrhage, retinal detachment, neovascular glaucoma, and ultimately severe vision loss [ 3 ]. Timely detection of the disease allows for its arrest or even regression through proper diabetes management and with anti-VEGF treatment, or laser therapy, thus averting visual impairment [ 4 ]. The American Academy of Ophthalmology (AAO) has outlined recommended follow-up intervals, advising screenings every 1–2 years for diabetics without any diabetic retinopathy (DR), annually for those with mild non-proliferative diabetic retinopathy (NPDR), every 6–9 months for moderate NPDR, and every 3–6 months for severe NPDR [ 5 ]. Indian guidelines classify individuals with no DR and mild NPDR as non-referable, reserving referral for those with more severe DR (moderate NPDR and above, with or without DME) [ 6 ]. Additionally, they emphasize the necessity for diabetes registries to ensure annual DR screenings. However, currently, no such recommendations exist in Pakistan from the Pakistan Diabetic Association or the Ophthalmological Society of Pakistan (OSP) regarding retinopathy and DME screening. The present study seeks to establish screening interval guidelines for early diagnosis, predicated on the emergence, progression, and regression patterns of retinal changes leading to various DR stages and DME. Materials and methods Study design This prospective longitudinal study was initiated at the Diabetic Clinic of Al Ibrahim Eye Hospital/Isra Postgraduate Institute of Ophthalmology Karachi in October 2021 and is projected to continue until October 2026. A preliminary report spanning 2 years is presented herein. The sample size was determined using OpenEpi sample software, considering a 28.78% prevalence of diabetic retinopathy with a 95% confidence interval [ 7 ]. Accordingly, the calculated sample size was 240. Sampling was conducted through convenience sampling methods. Patients were recruited from the diabetic clinic between October 2021 and March 2022 according to the inclusion and exclusion criteria. The grading of DR stages was performed utilizing the "international clinical diabetic retinopathy and diabetic macular edema disease severity scales" [ 8 ]. Inclusion criteria encompassed newly diagnosed type II diabetic patients exhibiting a normal fundus or NPDR of any stage, irrespective of age, gender, or glycemic status, who were willing to participate and consented to follow-ups. Exclusion criteria comprised patients with PDR, macular edema, non-visible fundus, or severe complications of diabetes such as renal failure. In the event of any patient developing vision-threatening diabetic retinopathy (VTDR) during the study period, necessary treatment was promptly initiated. Patients underwent a comprehensive examination, which included history-taking, visual acuity assessment using Snellen’s chart, and fundus examination conducted by an optometrist using a Non-Mydriatic fundus camera (Canon CR2). Subsequently, measurements of blood pressure (BP), weight, height, and random blood sugar (RBS) were taken. The status of diabetes control was evaluated by a diabetologist. The grading of DR was performed by a senior ophthalmologist and a medical retina consultant utilizing slit lamp 90D biomicroscopy. Detailed proforma were completed for each patient. Additionally, all patients underwent biochemical tests such as glycated hemoglobin (HbA1c), lipid profile, and serum creatinine. The test reports were collected and entered into the system by a counselor, and subsequently shared with the patients. If any changes in the treatment regimen were deemed necessary, individuals were scheduled to visit the diabetic clinic on a date convenient for both the patient and the diabetologist. The data of study patients were stratified into four groups: those who progressed, those who remained stable, those who regressed, and those who developed DME. These groups were then analyzed with respect to various biochemical parameters. In consideration of ethical concerns, the research team implemented an incentive program. Each participant in the study received free diabetic medications equivalent to three months' worth, along with transport allowances. This initiative significantly reduced dropouts from the study. Ethical approval and statistical analysis Prior approval was obtained from the hospital’s Research Ethics Committee, with the study protocol assigned the number REC/IPIO/2021/040-A. All principles of the Declaration of Helsinki were followed in compliance with the regulations of the professional code for Physicians. The data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 22.0. Mean ± standard deviation (S.D) was calculated for parametric data. After assessing normality through the Shapiro-Wilk test, the data for best-corrected visual acuity (BCVA) in logMAR were found to be non-parametric [ 9 ]. Therefore, median, and interquartile range (IQR) were computed for BCVA. The Kruskal-Wallis test was employed to compare BCVA among the different groups [ 10 ]. Additionally, the Chi-square test was utilized to examine the association between retinopathy stages and the duration of diabetes. For the comparison of means of biochemical parameters among groups, one-way ANOVA was performed. Post-hoc Tukey’s test was also employed to assess the significance between the means of each group. A p-value of ≤ 0.05 was considered statistically significant. Results A total of 251 patients were enrolled in this study, comprising 80 with a normal fundus, 59 with mild NPDR, 91 with moderate NPDR, and 21 with severe NPDR. Baseline characteristics and biochemical parameters of these patients are detailed in Table 1 . Table 1 Baseline characteristics Descriptive Normal Fundus (n = 80) Mild NPDR (n = 59) Moderate NPDR (n = 91) Severe NPDR (n = 21) P-value Age (yrs), Mean ± S.D 49.2 ± 9.36 50.98 ± 8.28 52.10 ± 7.58 52.01 ± 8.04 0.289 Male/Female n (%) 33 (41.2) / 47 (58.2) 29 (49.1) / 30 (50.9) 55 (60.4) / 36 (39.6) 13 (62) / 8 (38) 0.021 Duration of diabetes n (%) ≤ 5 yrs 44 (56.4) 14 (17.9) 13 (16.6) 7 (8.9) 0.001 6–10 yrs 20 (25) 26 (32.5) 30 (37.5) 4 (5) > 10 yrs 16 (19) 19 (22.6) 48 (57.1) 10 (11.9) Treatment n (%) Oral 55 (34.3) 40 (25) 51 (31.8) 14 (8.7) 0.003 Insulin 3 (11.1) 6 (22.2) 16 (59.2) 2 (7.4) Diet 10 (52.6) 5 (26.3) 3 (15.7) 1 (5.2) Combination 12 (26.6) 8 (17.7) 21 (46.6) 4 (8.8) Biochemical history (Mean ± S.D) RBS 216.67 ± 79.2 283.80 ± 104.40 308.13 ± 109.76 279.21 ± 88.02 0.027 HbA1c 10.05 ± 4.98 9.64 ± 2.61 9.93 ± 2.22 10.61 ± 1.97 0.311 Serum creatinine 0.93 ± 0.18 0.98 ± 0.94 0.94 ± 0.28 0.96 ± 0.18 0.452 HDL 35.67 ± 6.72 36.45 ± 8.94 34.68 ± 8.70 39.36 ± 6.40 0.189 LDL 129.04 ± 27.35 111.41 ± 29.31 128.85 ± 41.73 112.90 ± 32.27 0.037 TRIG 182.85 ± 96.8 196.35 ± 97.16 197.21 ± 121.67 156.81 ± 65.45 0.041 Among the 80 patients initially diagnosed with a normal fundus, 26 were lost to follow-up. Of the remaining 54 individuals, 46 (85.2%) maintained stable fundi over a 2-year period. However, 8 patients (14.8%) progressed to NPDR (Fig. 1 ). Among these cases, 6 developed mild NPDR and 2 exhibited moderate NPDR. The median time to the initial development of NPDR was 3.1 months. Notably, 3 out of the 6 mild NPDR cases regressed to a normal fundus within an average duration of 5 months. Regression from moderate NPDR to mild NPDR occurred within 5.5 months. No instances of DME were observed during the study period. A moderate positive correlation was identified between stable and progressive cases of HbA1c (r = 0.424, p > 0.05). Among the 59 patients with mild NPDR, 40 progressed to moderate NPDR, with a probability of 52.5%. The median time to the first incidence of moderate NPDR was 3.5 months. The likelihood of developing DME was 5% (2 out of 40) over a median time of 8 months. Among the 21 progressive cases, 10 regressed within an estimated duration of 4.6 months. A weak positive correlation was found between the HbA1c levels of mild NPDR patients and progression to the next stage (r = 0.064, p > 0.05). 91 patients diagnosed with moderate NPDR were monitored for fundus changes. Among the 54 cases that completed follow-ups the probability of progression to severe NPDR from moderate NPDR was 37.1% (20 out of 54), with a median time to the first incidence of severe NPDR of 4.5 months. Among the 20 progressive cases, 9 regressed, 8 to moderate NPDR with a median duration of 3.1 months, and one to mild NPDR. Similarly, the probability of progression to DME was 22.2% (12 out of 54), with a median time to the first incidence of DME being 7 months. A weak correlation was found between the HbA1c levels of moderate NPDR patients and progression to the next stage (r = 0.191, p > 0.05). 21 patients diagnosed with severe NPDR were monitored for fundus changes. Among the 16 cases observed, 5 remained stable, while 3 progressed to DME and 3 to DME with PDR. The probability of progression to DME was 37.5% (6 out of 16), with a median time to the first incidence of DME of 4.4 months. A moderate correlation was observed between the HbA1c levels of severe NPDR patients and progression to the next stage (r = 0.572, p > 0.05). These findings underscore the importance of regular monitoring and management of diabetic retinopathy, with particular attention to glycemic control as indicated by HbA1c levels. Duration of diabetes exhibited a significant association with different stages (p 10 yrs Progression 10 (26.3) 13 (34.2) 15 (39.5) 0.037 Stable 29 (35.8) 34 (42) 18 (22.2) Regression 16 (44.4) 7 (19.4) 13 (36.1) Developed DME 1 (8.3) 5 (41.7) 6 (50) In addition, significant results were observed for systolic blood pressure, random blood sugar, serum creatinine, and HDL levels among different stages (p < 0.05). Detailed findings are presented in Table 3 . Table 3 Comparison between different parameters among groups Systolic BP (n = 166) Diastolic BP (n = 166) Stage Mean ± S.D Stage Mean ± S.D p-value Stage Mean ± S.D Stage Mean ± S.D p-value P 131.84 ± 17.5 R 129.03 ± 13.82 0.434 P 82.97 ± 7.14 R 81.81 ± 9.42 0.746 S 124.20 ± 14.39 0.013 S 80.86 ± 6.55 0.306 DME 137.50 ± 19.60 0.27 DME 82.50 ± 7.53 0.958 R 129.03 ± 13.82 S 124.20 ± 14.39 0.12 R 81.81 ± 9.42 S 80.86 ± 6.55 0.529 DME 137.50 ± 19.60 0.102 DME 82.50 ± 7.53 0.78 S 124.20 ± 14.39 DME 137.50 ± 19.60 0.006 S 80.86 ± 6.55 DME 82.50 ± 7.53 0.479 Random Blood Sugar (RBS) (n = 166) HbA1c (n = 124) Stage Mean ± S.D Stage Mean ± S.D p-value Stage Mean ± S.D Stage Mean ± S.D p-value P 274.50 ± 79.95 R 226.33 ± 85.10 0.017 P 9.17 ± 1.99 R 7.80 ± 1.14 0.541 S 240.65 ± 87.45 0.047 S 9.90 ± 4.42 0.641 DME 297.58 ± 98.10 0.419 DME 9.66 ± 2.15 0.853 R 226.33 ± 85.10 S 240.65 ± 87.45 0.407 R 7.80 ± 1.14 S 9.90 ± 4.42 0.305 DD 297.58 ± 98.10 0.014 DME 9.66 ± 2.15 0.525 S 240.65 ± 87.45 DME 297.58 ± 98.10 0.034 S 80.86 ± 6.55 DME 9.66 ± 2.15 0.921 Serum Creatinine (n = 105) High-density lipoproteins (HDL) (n = 105) Stage Mean ± S.D Stage Mean ± S.D p-value Stage Mean ± S.D Stage Mean ± S.D p-value P 1.04 ± 0.53 R 0.95 ± 0.23 0.545 P 44.66 ± 27.18 R 36.10 ± 8.56 0.192 S 0.93 ± 0.24 0.232 S 35.53 ± 11.30 0.028 DME 1.25 ± 0.96 0.23 DME 45.12 ± 23.76 0.949 R 0.95 ± 0.23 S 0.93 ± 0.24 0.878 R 36.10 ± 8.56 S 35.53 ± 11.30 0.925 DME 1.25 ± 0.96 0.137 DME 45.12 ± 23.76 0.283 S 0.93 ± 0.24 DME 1.25 ± 0.96 0.045 S 35.53 ± 11.30 DME 45.12 ± 23.76 0.031 Low-density lipoproteins (LDL) (n = 105) Triglycerides (n = 105) Stage Mean ± S.D Stage Mean ± S.D p-value Stage Mean ± S.D Stage Mean ± S.D p-value P 114.11 ± 42.34 R 108.90 ± 25.75 0.743 P 208.85 ± 174.15 R 213.10 ± 109.82 0.926 S 124.61 ± 43.91 0.292 S 188.70 ± 97.36 0.474 DME 125.50 ± 51.88 0.51 DME 199.87 ± 54.56 0.854 R 108.90 ± 25.75 S 124.61 ± 43.91 0.285 R 213.10 ± 109.82 S 188.70 ± 97.36 0.558 DME 125.50 ± 51.88 0.416 DME 199.87 ± 54.56 0.819 S 124.61 ± 43.91 DME 125.50 ± 51.88 0.956 S 188.70 ± 97.36 DME 199.87 ± 54.56 0.807 Visual acuity was also compared across the four groups. A Kruskal-Wallis H test revealed a significant difference in best-corrected visual acuity (BCVA) among the four groups, χ2(3) = 23.527, p = 0.001. The median (interquartile range) BCVA was 0.3 (0.18) logMAR for the progression group, 0.2 (0.10) logMAR for the stable group, 0.2 (0) logMAR for the regression group, and 0.45 (2.20) logMAR for the group that developed diabetic macular edema (DME). These findings underscore the importance of considering various clinical parameters, including duration of diabetes, blood pressure, blood sugar levels, renal function, lipid profile, and visual acuity, in the management and prognosis of diabetic retinopathy. Discussion In this study, the likelihood of DR development in individuals with normal fundi was 14.8% within a median time of 3.1 months. The probability of progressing from mild NPDR to moderate NPDR was 52.5%, and from moderate NPDR to severe NPDR was 37.1%, with median durations of 3.5 and 4.5 months, respectively. Additionally, the likelihood of developing diabetic macular edema (DME) in mild, moderate, and severe NPDR cases was 5%, 22.2%, and 37.7%, respectively, with median durations of 8, 7, and 4.4 months over a span of two years. This indicates that if diabetics with normal fundus or mild NPDR are scheduled for follow-up after 1 year or longer, as suggested by the AAO [ 5 ] and Indian guidelines [ 6 ], there is a risk of missing the early diagnosis of mild NPDR in 14% of normal fundus cases, progression to moderate NPDR in 26%, and development of DME in 5% of mild NPDR cases. Therefore, it is advisable for diabetics with normal fundus and mild NPDR to undergo screening every 6 months instead of waiting for 1 year after the initial screening. The follow-up interval for moderate and severe NPDR is nearly in line with the AAO guidelines, which recommend 6–9 months for moderate NPDR and 3–6 months for severe NPDR [ 5 ]. However, it would be prudent to err on the side of caution by reducing the interval to 3–6 months for moderate NPDR and 3–4 months for severe NPDR. Moshfeghi and colleagues looking at pattern of DR progression in USA Clinical Practice demonstrated that over a 5-year period, the likelihood of progression from mild and moderate NPDR to severe NPDR was 5.8% and 17.6%, respectively, compared to 22.2% and 37.7% in our study [ 11 ]. The higher percentages observed in our study may be attributed to inadequate management of diabetes in our region or potentially influenced by genetic or ethnic factors, as suggested by studies from European countries. These studies have indicated an increased susceptibility of Asian populations to diabetes and DR. For instance, the prevalence of any DR was 37.4% in white Europeans compared to 42.35% in South Asians. Similarly, the prevalence of VTDR was 10.3% in South Asians compared to 5.5% in white Europeans [ 12 ]. In US Clinical Practice, the incidence of DME was reported to be 44.6% and 62.6% in moderate and severe NPDR, respectively, over a 5-year period [ 11 ]. In comparison, our present study found that 22.2% of patients with moderate NPDR and 37.8% with severe NPDR developed DME within 2 years. Given the difference in follow-up duration, it is plausible that within the next 3 years, we may observe similar figures. The development, progression, and regression of DR/ DME depend on both modifiable and non-modifiable risk factors. Modifiable risk factors for DR include chronic hyperglycemia, nephropathy, hypertension, and dyslipidemia. This study reveals significant differences among systolic blood pressure (BP) levels in progressing and regressing cases, as well as in stable and developed DME cases (p < 0.05). A similar relationship was demonstrated in a study by Liu and Co-workers from Singapore, where DR progression was associated with high systolic BP [ 13 ]. Regarding hyperglycemia, there were significant differences among RBS levels in progressive and regressive cases, as well as in progressive and stable cases (p < 0.05). However, no significant difference was found in any group with respect to HbA1c levels. A retrospective cohort study by Kim and colleagues found no significant differences in the proportion of progression to moderate NPDR or worse DR between individuals with high and low HbA1c levels [ 14 ]. Interestingly, HbA1c is more relevant to diabetes and coronary disease than to retinopathy [ 15 ]. It has also been reported that HbA1c is related to the prevalence of diabetic nephropathy but not to retinopathy [ 16 ]. In another study by Foo and Co-workers on Asian subjects with type 2 diabetes, it was found that HbA1c variability was not associated with the presence of moderate DR [ 17 ]. Significant differences in serum creatinine and high-density lipoproteins (HDL) levels (p < 0.05) were observed between stable fundus and developed DME cases. Another non-modifiable factor is the duration of diabetes; DR tends to become more progressive as the duration of diabetes increases. Our study indicates that 26.3%, 34.2%, and 39.5% of individuals in the progressive group had a duration of diabetes of 1–5 years, 6–10 years, and over 10 years, respectively. Similarly, DME also appears more frequently as the duration of diabetes increases. The study reveals that 8.3%, 41.7%, and 50% of individuals who developed DME had a duration of diabetes of 1–5 years, 6–10 years, and over 10 years, respectively (p < 0.05). Shrote and Diagavane in their work on Indian subjects demonstrated a significant association (p = 0.04) between the duration of diabetes and the severity of DR [ 18 ]. A similar relationship has been reported by Niazi and Colleagues from Pakistan as well (p < 0.05) [ 19 ]. The present study is notable for its observation of early development of DR as well as DME. The occurrence of DME in the first group (1–5 years) is unexpected. These changes manifest within a relatively short time frame of 3.1 to 4.5 months, even among individuals with less than five years of disease duration. The early emergence of microvascular changes can be attributed to the late diagnosis of the disease. In rural communities, individuals with diabetes often lack awareness of their condition, leading to delayed detection [ 20 ]. Given the observed accelerated progression of NPDR and development of DME, it is recommended to shorten the referral interval for subsequent screenings. Specifically, intervals of 6 months for individuals without DR and 3–6 months for all NPDR cases are advised. To facilitate early follow-up and mitigate the risk of diabetes-related blindness, policymakers, healthcare providers, and the community should collaborate to improve health education, raise awareness, and enhance the affordability of healthcare services. In essence, this study emphasizes the importance of regular screening, tailored follow-up intervals, and comprehensive management strategies to mitigate the progression of DR and its associated complications. Additionally, efforts to raise awareness and improve access to health care services, particularly in underserved populations, are crucial in addressing the early onset and rapid progression of diabetic eye disease. This study is limited by its single-center, tertiary-based design. Future research would benefit from community-based, multicenter studies to enhance generalizability. Additionally, the cost-effectiveness of frequent screenings should be explored. Fasting blood sugar (FBS) measurements were omitted due to logistical challenges faced by patients traveling long distances and experiencing lengthy waiting periods in hospital. Conclusion This study highlights the accelerated progression of various stages of NPDR and the development of DME within shorter durations, aligning with existing literature. Notably, progression was observed even in mild NPDR, with increasing frequency in moderate and severe NPDR cases. Declarations Acknowledgment: We also extend our gratitude to Abdul Rehman for his assistance in manuscript typing. Author contributions: P. Salim Mahar corrected and restructured the draft, providing critical review for intellectual content; Mohammad Daniyal Monis participated in critical review and contributed to the final manuscript for submission; M. Fahadullah collected data; Shahid Ahsan participated in initial writeup; M. Saleh Memon conceived the idea and prepared the initial draft. 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J Clin Diagn Res 9:NC10-4. https://doi.org/10.7860/JCDR/2015/12785.6689 Niazi MK AA, ; Naz MA,; Awan S. (2010) Duration of Diabetes as a Significant Factor for Retinopathy. pak J Ophthalmol [Internet] 26:https://doi.org/10.36351/pjo.v26i4.535 Memon MS MS, ; Sheikh SA,; Fahim MF. (2016) Community Perception and Service Utilization of Diabetic Retinopathy Management Project in Gaddap Town. pak J Ophthalmol [Internet] 32:https://doi.org/10.36351/pjo.v32i2.102 Footnotes HDL: High-density lipoproteins, LDL: Low-density lipoproteins, TRIG: Triglycerides P: Progression, R: Regression, S: Stationary Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Salim Mahar","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1UlEQVRIiWNgGAWjYFAC5oYDIMqAgYHxAQOYmUBICyNcC7MB0VoYoFrYJIjSIt9+sPHQDYZt8ubsZ59V/DhzmIGfPccArxaDM4kNh3MYbhvu7Ek3u9lz4zCDZM8bAloYIFoYNxxIY7vB8+Ewg8ENArbI9z8Ea7HfcP4ZW+EfoBZ7QloYbkBsSdxwI42NmQfoMAMJQn65AbLF4HbyhhvPmKVlzqTzSJx5VkDAYcmHP+dU3LbdcD6N8eObY9Zy/O3JG/A7DGIXgslDhPJRMApGwSgYBYQAAM0qUPxfLq2RAAAAAElFTkSuQmCC","orcid":"","institution":"Isra Postgraduate Institute of Ophthalmology","correspondingAuthor":true,"prefix":"","firstName":"P.","middleName":"Salim","lastName":"Mahar","suffix":""},{"id":306064362,"identity":"ed5a7567-b859-4ffc-8ec7-fb00b1dc32c0","order_by":1,"name":"Mohammad Daniyal Monis","email":"","orcid":"","institution":"Isra Postgraduate Institute of Ophthalmology","correspondingAuthor":false,"prefix":"","firstName":"Mohammad","middleName":"Daniyal","lastName":"Monis","suffix":""},{"id":306064363,"identity":"1e0d1b05-d148-41a9-8a12-584e5beea82d","order_by":2,"name":"M. Fahadullah Khan","email":"","orcid":"","institution":"Isra Postgraduate Institute of Ophthalmology","correspondingAuthor":false,"prefix":"","firstName":"M.","middleName":"Fahadullah","lastName":"Khan","suffix":""},{"id":306064364,"identity":"079624b0-a70b-4470-9992-11aba3a397d2","order_by":3,"name":"Shahid Ahsan","email":"","orcid":"","institution":"Isra Postgraduate Institute of Ophthalmology","correspondingAuthor":false,"prefix":"","firstName":"Shahid","middleName":"","lastName":"Ahsan","suffix":""},{"id":306064365,"identity":"cae4df39-6930-4384-a175-88f441d0a024","order_by":4,"name":"M. Saleh Memon","email":"","orcid":"","institution":"Isra Postgraduate Institute of Ophthalmology","correspondingAuthor":false,"prefix":"","firstName":"M.","middleName":"Saleh","lastName":"Memon","suffix":""}],"badges":[],"createdAt":"2024-05-21 06:10:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4452499/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4452499/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":57954000,"identity":"e141a2ba-1558-45c2-bf70-df097d4b9cd1","added_by":"auto","created_at":"2024-06-07 23:12:58","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":59333,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart for progression, regression and DME development.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4452499/v1/b41321ee26a6b26a9f5cedd2.png"},{"id":58403533,"identity":"128d7ae9-5980-4145-8a25-9c534e744970","added_by":"auto","created_at":"2024-06-15 05:54:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":786476,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4452499/v1/1283a7af-744d-4c9e-9a46-ea5d0313078b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Occurrence and Advancement of Diabetic Retinopathy in a Tertiary Care Setting: A Preliminary Report with Initial Overview and Recommended Protocols for Subsequent Screening","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePakistan currently ranks third in the world for diabetes prevalence, trailing only China and India. With nearly 33\u0026nbsp;million individuals affected, this number is projected to soar to 629\u0026nbsp;million globally by 2045 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Approximately one in three adults in Pakistan is estimated to have diabetes, with many being diagnosed with type 2 diabetes during their working years, while others are diagnosed only after complications arise.\u003c/p\u003e \u003cp\u003eAs the prevalence of diabetes continues to escalate exponentially, the incidence of diabetic eye complications is expected to follow suit. Diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) stand out as the most common causes of diabetes-related vision loss. DME arises from vessel leakage leading to edema, while proliferative diabetic retinopathy results from retinal ischemia fostering neovascularization and culminating in vitreous hemorrhage, retinal detachment, neovascular glaucoma, and ultimately severe vision loss [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Timely detection of the disease allows for its arrest or even regression through proper diabetes management and with anti-VEGF treatment, or laser therapy, thus averting visual impairment [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe American Academy of Ophthalmology (AAO) has outlined recommended follow-up intervals, advising screenings every 1\u0026ndash;2 years for diabetics without any diabetic retinopathy (DR), annually for those with mild non-proliferative diabetic retinopathy (NPDR), every 6\u0026ndash;9 months for moderate NPDR, and every 3\u0026ndash;6 months for severe NPDR [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Indian guidelines classify individuals with no DR and mild NPDR as non-referable, reserving referral for those with more severe DR (moderate NPDR and above, with or without DME) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Additionally, they emphasize the necessity for diabetes registries to ensure annual DR screenings. However, currently, no such recommendations exist in Pakistan from the Pakistan Diabetic Association or the Ophthalmological Society of Pakistan (OSP) regarding retinopathy and DME screening.\u003c/p\u003e \u003cp\u003e The present study seeks to establish screening interval guidelines for early diagnosis, predicated on the emergence, progression, and regression patterns of retinal changes leading to various DR stages and DME.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003eStudy design\u003c/h2\u003e\n \u003cp\u003eThis prospective longitudinal study was initiated at the Diabetic Clinic of Al Ibrahim Eye Hospital/Isra Postgraduate Institute of Ophthalmology Karachi in October 2021 and is projected to continue until October 2026. A preliminary report spanning 2 years is presented herein. The sample size was determined using OpenEpi sample software, considering a 28.78% prevalence of diabetic retinopathy with a 95% confidence interval [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e]. Accordingly, the calculated sample size was 240. Sampling was conducted through convenience sampling methods. Patients were recruited from the diabetic clinic between October 2021 and March 2022 according to the inclusion and exclusion criteria.\u003c/p\u003e\n \u003cp\u003eThe grading of DR stages was performed utilizing the \u0026quot;international clinical diabetic retinopathy and diabetic macular edema disease severity scales\u0026quot; [\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e]. Inclusion criteria encompassed newly diagnosed type II diabetic patients exhibiting a normal fundus or NPDR of any stage, irrespective of age, gender, or glycemic status, who were willing to participate and consented to follow-ups. Exclusion criteria comprised patients with PDR, macular edema, non-visible fundus, or severe complications of diabetes such as renal failure. In the event of any patient developing vision-threatening diabetic retinopathy (VTDR) during the study period, necessary treatment was promptly initiated.\u003c/p\u003e\n \u003cp\u003ePatients underwent a comprehensive examination, which included history-taking, visual acuity assessment using Snellen\u0026rsquo;s chart, and fundus examination conducted by an optometrist using a Non-Mydriatic fundus camera (Canon CR2). Subsequently, measurements of blood pressure (BP), weight, height, and random blood sugar (RBS) were taken. The status of diabetes control was evaluated by a diabetologist. The grading of DR was performed by a senior ophthalmologist and a medical retina consultant utilizing slit lamp 90D biomicroscopy. Detailed proforma were completed for each patient. Additionally, all patients underwent biochemical tests such as glycated hemoglobin (HbA1c), lipid profile, and serum creatinine. The test reports were collected and entered into the system by a counselor, and subsequently shared with the patients. If any changes in the treatment regimen were deemed necessary, individuals were scheduled to visit the diabetic clinic on a date convenient for both the patient and the diabetologist.\u003c/p\u003e\n \u003cp\u003eThe data of study patients were stratified into four groups: those who progressed, those who remained stable, those who regressed, and those who developed DME. These groups were then analyzed with respect to various biochemical parameters.\u003c/p\u003e\n \u003cp\u003eIn consideration of ethical concerns, the research team implemented an incentive program. Each participant in the study received free diabetic medications equivalent to three months\u0026apos; worth, along with transport allowances. This initiative significantly reduced dropouts from the study.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eEthical approval\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eand statistical analysis\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePrior approval was obtained from the hospital\u0026rsquo;s Research Ethics Committee, with the study protocol assigned the number REC/IPIO/2021/040-A. All principles of the Declaration of Helsinki were followed in compliance with the regulations of the professional code for Physicians. The data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 22.0. Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (S.D) was calculated for parametric data. After assessing normality through the Shapiro-Wilk test, the data for best-corrected visual acuity (BCVA) in logMAR were found to be non-parametric [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e]. Therefore, median, and interquartile range (IQR) were computed for BCVA. The Kruskal-Wallis test was employed to compare BCVA among the different groups [\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e]. Additionally, the Chi-square test was utilized to examine the association between retinopathy stages and the duration of diabetes. For the comparison of means of biochemical parameters among groups, one-way ANOVA was performed. Post-hoc Tukey\u0026rsquo;s test was also employed to assess the significance between the means of each group. A p-value of \u0026le;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 251 patients were enrolled in this study, comprising 80 with a normal fundus, 59 with mild NPDR, 91 with moderate NPDR, and 21 with severe NPDR. Baseline characteristics and biochemical parameters of these patients are detailed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics\u003ca class=\"FNLink\" href=\"#Fn1\" id=\"#FNLinkFn1\"\u003e\u003c/a\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eDescriptive\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNormal Fundus (n\u0026thinsp;=\u0026thinsp;80)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMild NPDR\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;59)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eModerate NPDR (n\u0026thinsp;=\u0026thinsp;91)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSevere NPDR (n\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (yrs), Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.D\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50.98\u0026thinsp;\u0026plusmn;\u0026thinsp;8.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e52.10\u0026thinsp;\u0026plusmn;\u0026thinsp;7.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e52.01\u0026thinsp;\u0026plusmn;\u0026thinsp;8.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.289\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale/Female n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (41.2) / 47 (58.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (49.1) / 30 (50.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e55 (60.4) / 36 (39.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13 (62) / 8 (38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDuration of diabetes n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;5 yrs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (56.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (17.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (16.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (8.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u0026ndash;10 yrs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (32.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30 (37.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;10 yrs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (22.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48 (57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (11.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTreatment n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55 (34.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51 (31.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14 (8.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInsulin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (22.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (59.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (7.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (52.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (26.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (15.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (5.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCombination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (26.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (17.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (46.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (8.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBiochemical history (Mean\u003c/b\u003e\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;\u003cb\u003eS.D)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRBS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e216.67\u0026thinsp;\u0026plusmn;\u0026thinsp;79.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e283.80\u0026thinsp;\u0026plusmn;\u0026thinsp;104.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e308.13\u0026thinsp;\u0026plusmn;\u0026thinsp;109.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e279.21\u0026thinsp;\u0026plusmn;\u0026thinsp;88.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHbA1c\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.05\u0026thinsp;\u0026plusmn;\u0026thinsp;4.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.64\u0026thinsp;\u0026plusmn;\u0026thinsp;2.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.93\u0026thinsp;\u0026plusmn;\u0026thinsp;2.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.61\u0026thinsp;\u0026plusmn;\u0026thinsp;1.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.311\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum creatinine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.96\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.452\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHDL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35.67\u0026thinsp;\u0026plusmn;\u0026thinsp;6.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.45\u0026thinsp;\u0026plusmn;\u0026thinsp;8.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34.68\u0026thinsp;\u0026plusmn;\u0026thinsp;8.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e39.36\u0026thinsp;\u0026plusmn;\u0026thinsp;6.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.189\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e129.04\u0026thinsp;\u0026plusmn;\u0026thinsp;27.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e111.41\u0026thinsp;\u0026plusmn;\u0026thinsp;29.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e128.85\u0026thinsp;\u0026plusmn;\u0026thinsp;41.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e112.90\u0026thinsp;\u0026plusmn;\u0026thinsp;32.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.037\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTRIG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e182.85\u0026thinsp;\u0026plusmn;\u0026thinsp;96.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e196.35\u0026thinsp;\u0026plusmn;\u0026thinsp;97.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e197.21\u0026thinsp;\u0026plusmn;\u0026thinsp;121.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e156.81\u0026thinsp;\u0026plusmn;\u0026thinsp;65.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.041\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAmong the 80 patients initially diagnosed with a normal fundus, 26 were lost to follow-up. Of the remaining 54 individuals, 46 (85.2%) maintained stable fundi over a 2-year period. However, 8 patients (14.8%) progressed to NPDR (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAmong these cases, 6 developed mild NPDR and 2 exhibited moderate NPDR. The median time to the initial development of NPDR was 3.1 months. Notably, 3 out of the 6 mild NPDR cases regressed to a normal fundus within an average duration of 5 months. Regression from moderate NPDR to mild NPDR occurred within 5.5 months. No instances of DME were observed during the study period. A moderate positive correlation was identified between stable and progressive cases of HbA1c (r\u0026thinsp;=\u0026thinsp;0.424, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eAmong the 59 patients with mild NPDR, 40 progressed to moderate NPDR, with a probability of 52.5%. The median time to the first incidence of moderate NPDR was 3.5 months. The likelihood of developing DME was 5% (2 out of 40) over a median time of 8 months. Among the 21 progressive cases, 10 regressed within an estimated duration of 4.6 months. A weak positive correlation was found between the HbA1c levels of mild NPDR patients and progression to the next stage (r\u0026thinsp;=\u0026thinsp;0.064, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e91 patients diagnosed with moderate NPDR were monitored for fundus changes. Among the 54 cases that completed follow-ups the probability of progression to severe NPDR from moderate NPDR was 37.1% (20 out of 54), with a median time to the first incidence of severe NPDR of 4.5 months. Among the 20 progressive cases, 9 regressed, 8 to moderate NPDR with a median duration of 3.1 months, and one to mild NPDR. Similarly, the probability of progression to DME was 22.2% (12 out of 54), with a median time to the first incidence of DME being 7 months. A weak correlation was found between the HbA1c levels of moderate NPDR patients and progression to the next stage (r\u0026thinsp;=\u0026thinsp;0.191, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e21 patients diagnosed with severe NPDR were monitored for fundus changes. Among the 16 cases observed, 5 remained stable, while 3 progressed to DME and 3 to DME with PDR. The probability of progression to DME was 37.5% (6 out of 16), with a median time to the first incidence of DME of 4.4 months. A moderate correlation was observed between the HbA1c levels of severe NPDR patients and progression to the next stage (r\u0026thinsp;=\u0026thinsp;0.572, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eThese findings underscore the importance of regular monitoring and management of diabetic retinopathy, with particular attention to glycemic control as indicated by HbA1c levels. Duration of diabetes exhibited a significant association with different stages (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), as indicated in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociation of duration of diabetes with different stages\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eStages\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eDuration of Diabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u0026ndash;5 yrs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u0026ndash;10 yrs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;10 yrs\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProgression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (26.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (34.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (39.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.037\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (35.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (22.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRegression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (44.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (19.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (36.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeveloped DME\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (8.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (41.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn addition, significant results were observed for systolic blood pressure, random blood sugar, serum creatinine, and HDL levels among different stages (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Detailed findings are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison between different parameters among groups\u003ca class=\"FNLink\" href=\"#Fn2\" id=\"#FNLinkFn2\"\u003e\u003c/a\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eSystolic BP (n\u0026thinsp;=\u0026thinsp;166)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c10\" namest=\"c6\"\u003e \u003cp\u003eDiastolic BP (n\u0026thinsp;=\u0026thinsp;166)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.D\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStage\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.D\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eStage\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.D\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eStage\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.D\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eP\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e131.84\u0026thinsp;\u0026plusmn;\u0026thinsp;17.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e129.03\u0026thinsp;\u0026plusmn;\u0026thinsp;13.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.434\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eP\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e82.97\u0026thinsp;\u0026plusmn;\u0026thinsp;7.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e81.81\u0026thinsp;\u0026plusmn;\u0026thinsp;9.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.746\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e124.20\u0026thinsp;\u0026plusmn;\u0026thinsp;14.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.013\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e80.86\u0026thinsp;\u0026plusmn;\u0026thinsp;6.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.306\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eDME\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e137.50\u0026thinsp;\u0026plusmn;\u0026thinsp;19.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eDME\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e82.50\u0026thinsp;\u0026plusmn;\u0026thinsp;7.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.958\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e129.03\u0026thinsp;\u0026plusmn;\u0026thinsp;13.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e124.20\u0026thinsp;\u0026plusmn;\u0026thinsp;14.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e81.81\u0026thinsp;\u0026plusmn;\u0026thinsp;9.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e80.86\u0026thinsp;\u0026plusmn;\u0026thinsp;6.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.529\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eDME\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e137.50\u0026thinsp;\u0026plusmn;\u0026thinsp;19.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.102\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eDME\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e82.50\u0026thinsp;\u0026plusmn;\u0026thinsp;7.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e124.20\u0026thinsp;\u0026plusmn;\u0026thinsp;14.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eDME\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e137.50\u0026thinsp;\u0026plusmn;\u0026thinsp;19.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.006\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e80.86\u0026thinsp;\u0026plusmn;\u0026thinsp;6.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eDME\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e82.50\u0026thinsp;\u0026plusmn;\u0026thinsp;7.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.479\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRandom Blood Sugar (RBS) (n\u0026thinsp;=\u0026thinsp;166)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c10\" namest=\"c6\"\u003e \u003cp\u003e\u003cb\u003eHbA1c (n\u0026thinsp;=\u0026thinsp;124)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.D\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eStage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.D\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003ep-value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eStage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.D\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eStage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.D\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003ep-value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eP\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e274.50\u0026thinsp;\u0026plusmn;\u0026thinsp;79.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e226.33\u0026thinsp;\u0026plusmn;\u0026thinsp;85.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.017\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eP\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e9.17\u0026thinsp;\u0026plusmn;\u0026thinsp;1.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7.80\u0026thinsp;\u0026plusmn;\u0026thinsp;1.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.541\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e240.65\u0026thinsp;\u0026plusmn;\u0026thinsp;87.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.047\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e9.90\u0026thinsp;\u0026plusmn;\u0026thinsp;4.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.641\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eDME\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e297.58\u0026thinsp;\u0026plusmn;\u0026thinsp;98.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.419\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eDME\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e9.66\u0026thinsp;\u0026plusmn;\u0026thinsp;2.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.853\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e226.33\u0026thinsp;\u0026plusmn;\u0026thinsp;85.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e240.65\u0026thinsp;\u0026plusmn;\u0026thinsp;87.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.407\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e7.80\u0026thinsp;\u0026plusmn;\u0026thinsp;1.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e9.90\u0026thinsp;\u0026plusmn;\u0026thinsp;4.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.305\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eDD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e297.58\u0026thinsp;\u0026plusmn;\u0026thinsp;98.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.014\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eDME\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e9.66\u0026thinsp;\u0026plusmn;\u0026thinsp;2.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.525\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e240.65\u0026thinsp;\u0026plusmn;\u0026thinsp;87.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eDME\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e297.58\u0026thinsp;\u0026plusmn;\u0026thinsp;98.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.034\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e80.86\u0026thinsp;\u0026plusmn;\u0026thinsp;6.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eDME\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e9.66\u0026thinsp;\u0026plusmn;\u0026thinsp;2.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.921\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSerum Creatinine (n\u0026thinsp;=\u0026thinsp;105)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c10\" namest=\"c6\"\u003e \u003cp\u003e\u003cb\u003eHigh-density lipoproteins (HDL) (n\u0026thinsp;=\u0026thinsp;105)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.D\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eStage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.D\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003ep-value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eStage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.D\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eStage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.D\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003ep-value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eP\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e1.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.95\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.545\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eP\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e44.66\u0026thinsp;\u0026plusmn;\u0026thinsp;27.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e36.10\u0026thinsp;\u0026plusmn;\u0026thinsp;8.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.192\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.232\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e35.53\u0026thinsp;\u0026plusmn;\u0026thinsp;11.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003e0.028\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eDME\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eDME\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e45.12\u0026thinsp;\u0026plusmn;\u0026thinsp;23.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.949\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.95\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.878\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e36.10\u0026thinsp;\u0026plusmn;\u0026thinsp;8.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e35.53\u0026thinsp;\u0026plusmn;\u0026thinsp;11.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.925\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eDME\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.137\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eDME\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e45.12\u0026thinsp;\u0026plusmn;\u0026thinsp;23.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.283\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eDME\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003e0.045\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e35.53\u0026thinsp;\u0026plusmn;\u0026thinsp;11.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eDME\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e45.12\u0026thinsp;\u0026plusmn;\u0026thinsp;23.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003e0.031\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLow-density lipoproteins (LDL) (n\u0026thinsp;=\u0026thinsp;105)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c10\" namest=\"c6\"\u003e \u003cp\u003e\u003cb\u003eTriglycerides (n\u0026thinsp;=\u0026thinsp;105)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.D\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eStage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.D\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003ep-value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eStage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.D\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eStage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.D\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003ep-value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eP\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e114.11\u0026thinsp;\u0026plusmn;\u0026thinsp;42.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e108.90\u0026thinsp;\u0026plusmn;\u0026thinsp;25.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.743\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eP\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e208.85\u0026thinsp;\u0026plusmn;\u0026thinsp;174.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e213.10\u0026thinsp;\u0026plusmn;\u0026thinsp;109.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.926\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e124.61\u0026thinsp;\u0026plusmn;\u0026thinsp;43.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.292\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e188.70\u0026thinsp;\u0026plusmn;\u0026thinsp;97.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.474\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eDME\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e125.50\u0026thinsp;\u0026plusmn;\u0026thinsp;51.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eDME\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e199.87\u0026thinsp;\u0026plusmn;\u0026thinsp;54.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.854\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e108.90\u0026thinsp;\u0026plusmn;\u0026thinsp;25.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e124.61\u0026thinsp;\u0026plusmn;\u0026thinsp;43.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.285\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e213.10\u0026thinsp;\u0026plusmn;\u0026thinsp;109.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e188.70\u0026thinsp;\u0026plusmn;\u0026thinsp;97.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.558\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eDME\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e125.50\u0026thinsp;\u0026plusmn;\u0026thinsp;51.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.416\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eDME\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e199.87\u0026thinsp;\u0026plusmn;\u0026thinsp;54.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.819\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e124.61\u0026thinsp;\u0026plusmn;\u0026thinsp;43.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eDME\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e125.50\u0026thinsp;\u0026plusmn;\u0026thinsp;51.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.956\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e188.70\u0026thinsp;\u0026plusmn;\u0026thinsp;97.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eDME\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e199.87\u0026thinsp;\u0026plusmn;\u0026thinsp;54.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.807\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eVisual acuity was also compared across the four groups. A Kruskal-Wallis H test revealed a significant difference in best-corrected visual acuity (BCVA) among the four groups, χ2(3)\u0026thinsp;=\u0026thinsp;23.527, p\u0026thinsp;=\u0026thinsp;0.001. The median (interquartile range) BCVA was 0.3 (0.18) logMAR for the progression group, 0.2 (0.10) logMAR for the stable group, 0.2 (0) logMAR for the regression group, and 0.45 (2.20) logMAR for the group that developed diabetic macular edema (DME).\u003c/p\u003e \u003cp\u003eThese findings underscore the importance of considering various clinical parameters, including duration of diabetes, blood pressure, blood sugar levels, renal function, lipid profile, and visual acuity, in the management and prognosis of diabetic retinopathy.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, the likelihood of DR development in individuals with normal fundi was 14.8% within a median time of 3.1 months. The probability of progressing from mild NPDR to moderate NPDR was 52.5%, and from moderate NPDR to severe NPDR was 37.1%, with median durations of 3.5 and 4.5 months, respectively. Additionally, the likelihood of developing diabetic macular edema (DME) in mild, moderate, and severe NPDR cases was 5%, 22.2%, and 37.7%, respectively, with median durations of 8, 7, and 4.4 months over a span of two years.\u003c/p\u003e \u003cp\u003eThis indicates that if diabetics with normal fundus or mild NPDR are scheduled for follow-up after 1 year or longer, as suggested by the AAO [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] and Indian guidelines [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], there is a risk of missing the early diagnosis of mild NPDR in 14% of normal fundus cases, progression to moderate NPDR in 26%, and development of DME in 5% of mild NPDR cases. Therefore, it is advisable for diabetics with normal fundus and mild NPDR to undergo screening every 6 months instead of waiting for 1 year after the initial screening.\u003c/p\u003e \u003cp\u003eThe follow-up interval for moderate and severe NPDR is nearly in line with the AAO guidelines, which recommend 6\u0026ndash;9 months for moderate NPDR and 3\u0026ndash;6 months for severe NPDR [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, it would be prudent to err on the side of caution by reducing the interval to 3\u0026ndash;6 months for moderate NPDR and 3\u0026ndash;4 months for severe NPDR.\u003c/p\u003e \u003cp\u003eMoshfeghi and colleagues looking at pattern of DR progression in USA Clinical Practice demonstrated that over a 5-year period, the likelihood of progression from mild and moderate NPDR to severe NPDR was 5.8% and 17.6%, respectively, compared to 22.2% and 37.7% in our study [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The higher percentages observed in our study may be attributed to inadequate management of diabetes in our region or potentially influenced by genetic or ethnic factors, as suggested by studies from European countries. These studies have indicated an increased susceptibility of Asian populations to diabetes and DR. For instance, the prevalence of any DR was 37.4% in white Europeans compared to 42.35% in South Asians. Similarly, the prevalence of VTDR was 10.3% in South Asians compared to 5.5% in white Europeans [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn US Clinical Practice, the incidence of DME was reported to be 44.6% and 62.6% in moderate and severe NPDR, respectively, over a 5-year period [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In comparison, our present study found that 22.2% of patients with moderate NPDR and 37.8% with severe NPDR developed DME within 2 years. Given the difference in follow-up duration, it is plausible that within the next 3 years, we may observe similar figures.\u003c/p\u003e \u003cp\u003eThe development, progression, and regression of DR/ DME depend on both modifiable and non-modifiable risk factors. Modifiable risk factors for DR include chronic hyperglycemia, nephropathy, hypertension, and dyslipidemia. This study reveals significant differences among systolic blood pressure (BP) levels in progressing and regressing cases, as well as in stable and developed DME cases (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). A similar relationship was demonstrated in a study by Liu and Co-workers from Singapore, where DR progression was associated with high systolic BP [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Regarding hyperglycemia, there were significant differences among RBS levels in progressive and regressive cases, as well as in progressive and stable cases (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). However, no significant difference was found in any group with respect to HbA1c levels. A retrospective cohort study by Kim and colleagues found no significant differences in the proportion of progression to moderate NPDR or worse DR between individuals with high and low HbA1c levels [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Interestingly, HbA1c is more relevant to diabetes and coronary disease than to retinopathy [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. It has also been reported that HbA1c is related to the prevalence of diabetic nephropathy but not to retinopathy [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In another study by Foo and Co-workers on Asian subjects with type 2 diabetes, it was found that HbA1c variability was not associated with the presence of moderate DR [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Significant differences in serum creatinine and high-density lipoproteins (HDL) levels (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) were observed between stable fundus and developed DME cases.\u003c/p\u003e \u003cp\u003eAnother non-modifiable factor is the duration of diabetes; DR tends to become more progressive as the duration of diabetes increases. Our study indicates that 26.3%, 34.2%, and 39.5% of individuals in the progressive group had a duration of diabetes of 1\u0026ndash;5 years, 6\u0026ndash;10 years, and over 10 years, respectively. Similarly, DME also appears more frequently as the duration of diabetes increases. The study reveals that 8.3%, 41.7%, and 50% of individuals who developed DME had a duration of diabetes of 1\u0026ndash;5 years, 6\u0026ndash;10 years, and over 10 years, respectively (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Shrote and Diagavane in their work on Indian subjects demonstrated a significant association (p\u0026thinsp;=\u0026thinsp;0.04) between the duration of diabetes and the severity of DR [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. A similar relationship has been reported by Niazi and Colleagues from Pakistan as well (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe present study is notable for its observation of early development of DR as well as DME. The occurrence of DME in the first group (1\u0026ndash;5 years) is unexpected. These changes manifest within a relatively short time frame of 3.1 to 4.5 months, even among individuals with less than five years of disease duration. The early emergence of microvascular changes can be attributed to the late diagnosis of the disease. In rural communities, individuals with diabetes often lack awareness of their condition, leading to delayed detection [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGiven the observed accelerated progression of NPDR and development of DME, it is recommended to shorten the referral interval for subsequent screenings. Specifically, intervals of 6 months for individuals without DR and 3\u0026ndash;6 months for all NPDR cases are advised. To facilitate early follow-up and mitigate the risk of diabetes-related blindness, policymakers, healthcare providers, and the community should collaborate to improve health education, raise awareness, and enhance the affordability of healthcare services.\u003c/p\u003e \u003cp\u003eIn essence, this study emphasizes the importance of regular screening, tailored follow-up intervals, and comprehensive management strategies to mitigate the progression of DR and its associated complications. Additionally, efforts to raise awareness and improve access to health care services, particularly in underserved populations, are crucial in addressing the early onset and rapid progression of diabetic eye disease.\u003c/p\u003e \u003cp\u003eThis study is limited by its single-center, tertiary-based design. Future research would benefit from community-based, multicenter studies to enhance generalizability. Additionally, the cost-effectiveness of frequent screenings should be explored. Fasting blood sugar (FBS) measurements were omitted due to logistical challenges faced by patients traveling long distances and experiencing lengthy waiting periods in hospital.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study highlights the accelerated progression of various stages of NPDR and the development of DME within shorter durations, aligning with existing literature. Notably, progression was observed even in mild NPDR, with increasing frequency in moderate and severe NPDR cases.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgment:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe also extend our gratitude to Abdul Rehman for his assistance in manuscript typing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eP. Salim Mahar corrected and restructured the draft, providing critical review for intellectual content; Mohammad Daniyal Monis participated in critical review and contributed to the final manuscript for submission; M. Fahadullah collected data; Shahid Ahsan participated in initial writeup; M. Saleh Memon conceived the idea and prepared the initial draft. All authors have reviewed and approved the final version of the manuscript for publication.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAzeem S, Khan U, Liaquat A. (2022) The increasing rate of diabetes in Pakistan: A silent killer. Ann Med Surg (Lond) 79:103901. https://doi.org/10.1016/j.amsu.2022.103901\u003c/li\u003e\n\u003cli\u003eProf. Dr. Taj J. (2023) Diabetes Mellitus \u0026ndash; The Epidemic of 21 Century. Esculapio Journal of SIMS 19:1-2.\u003c/li\u003e\n\u003cli\u003eShukla UV, Tripathy K. Diabetic Retinopathy. StatPearls. Treasure Island (FL)2024.\u003c/li\u003e\n\u003cli\u003eEllis D, Burgess PI, Kayange P. (2013) Management of diabetic retinopathy. Malawi Med J 25:116-20.\u003c/li\u003e\n\u003cli\u003eSolomon SD, Chew E, Duh EJ, Sobrin L, Sun JK, VanderBeek BL, et al. (2017) Diabetic Retinopathy: A Position Statement by the American Diabetes Association. 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PLoS One 7:e32182. https://doi.org/10.1371/journal.pone.0032182\u003c/li\u003e\n\u003cli\u003eLiu L, Quang ND, Banu R, Kumar H, Tham YC, Cheng CY, et al. (2020) Hypertension, blood pressure control and diabetic retinopathy in a large population-based study. PLoS One 15:e0229665. https://doi.org/10.1371/journal.pone.0229665\u003c/li\u003e\n\u003cli\u003eKim HU, Park SP, Kim YK. (2021) Long-term HbA1c variability and the development and progression of diabetic retinopathy in subjects with type 2 diabetes. Sci Rep 11:4731. https://doi.org/10.1038/s41598-021-84150-8\u003c/li\u003e\n\u003cli\u003eSherwani SI, Khan HA, Ekhzaimy A, Masood A, Sakharkar MK. (2016) Significance of HbA1c Test in Diagnosis and Prognosis of Diabetic Patients. Biomark Insights 11:95-104. https://doi.org/10.4137/BMI.S38440\u003c/li\u003e\n\u003cli\u003ePenno G, Solini A, Bonora E, Fondelli C, Orsi E, Zerbini G, et al. (2013) HbA1c variability as an independent correlate of nephropathy, but not retinopathy, in patients with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicenter study. Diabetes Care 36:2301-10. https://doi.org/10.2337/dc12-2264\u003c/li\u003e\n\u003cli\u003eFoo V, Quah J, Cheung G, Tan NC, Ma Zar KL, Chan CM, et al. (2017) HbA1c, systolic blood pressure variability and diabetic retinopathy in Asian type 2 diabetics. J Diabetes 9:200-7. https://doi.org/10.1111/1753-0407.12403\u003c/li\u003e\n\u003cli\u003eShrote AP, Diagavane S. (2015) Clinical Evaluation of Correlation Between Diabetic Retinopathy with Modifiable, Non-Modifiable and Other Independent Risk Factors in Tertiary Set-up in Central Rural India. J Clin Diagn Res 9:NC10-4. https://doi.org/10.7860/JCDR/2015/12785.6689\u003c/li\u003e\n\u003cli\u003eNiazi MK AA, ; Naz MA,; Awan S. (2010) Duration of Diabetes as a Significant Factor for Retinopathy. pak J Ophthalmol [Internet] 26:https://doi.org/10.36351/pjo.v26i4.535\u003c/li\u003e\n\u003cli\u003eMemon MS MS, ; Sheikh SA,; Fahim MF. (2016) Community Perception and Service Utilization of Diabetic Retinopathy Management Project in Gaddap Town. pak J Ophthalmol [Internet] 32:https://doi.org/10.36351/pjo.v32i2.102\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Footnotes","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003e HDL: High-density lipoproteins, LDL: Low-density lipoproteins, TRIG: Triglycerides\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e P: Progression, R: Regression, S: Stationary\u003c/span\u003e\u003c/li\u003e\u003c/ol\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":"Diabetes Mellitus, Diabetic Macular Edema, Non-Proliferative Diabetic Retinopathy, Proliferative Diabetic Retinopathy, Vision Screening","lastPublishedDoi":"10.21203/rs.3.rs-4452499/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4452499/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground/Aims\u003c/b\u003e\u003c/p\u003e \u003cp\u003e The objective of this study is to evaluate diabetic patients with either a normal fundus or non-proliferative diabetic retinopathy (NPDR) changes, examining retinal alterations during follow-up, and proposing follow-up guidelines within a tertiary eye care setting.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eA 5-year prospective longitudinal study is being conducted at the Diabetic Clinic of Al Ibrahim Eye Hospital/Isra Postgraduate Institute of Ophthalmology, Karachi. Induction for the research took place from October 2021 to March 2022, and a 2-year preliminary report is presented here. Newly diagnosed type II diabetic patients with normal fundus or NPDR of any stage, irrespective of age, gender, or glycemic status, who were willing to participate and agreed to follow-ups, were included. Patients with proliferative diabetic retinopathy (PDR), diabetic macular edema (DME), fundus non-visibility, or systemic complications of diabetes were excluded.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eA total of 251 patients were enrolled, consisting of 80 individuals with a normal fundus and 171 with different stages of NPDR, including mild (n\u0026thinsp;=\u0026thinsp;59), moderate (n\u0026thinsp;=\u0026thinsp;91), and severe (n\u0026thinsp;=\u0026thinsp;21) retinopathy. The incidence of progression from mild to moderate NPDR was noted to be 52.5%, with a median time of 3.5 months. Progression from moderate to severe NPDR occurred in 37.1% of cases, with a median time of 4.5 months. Similarly, DME developed in 5% of patients with mild NPDR over 8 months, in 22.2% with moderate NPDR over 7 months, and in 37.5% with severe NPDR over 4.4 months.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis study suggests that the incidence and progression of NPDR stages, along with the development of DME, may occur in a shorter duration in diabetic patients compared to what is suggested in existing literature.\u003c/p\u003e","manuscriptTitle":"Occurrence and Advancement of Diabetic Retinopathy in a Tertiary Care Setting: A Preliminary Report with Initial Overview and Recommended Protocols for Subsequent Screening","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-07 23:12:54","doi":"10.21203/rs.3.rs-4452499/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":"59459b08-3d49-4733-b6be-a4470291b95e","owner":[],"postedDate":"June 7th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-15T05:46:29+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-07 23:12:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4452499","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4452499","identity":"rs-4452499","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}