Diabetic Retinopathy (DR) is one of the most common and severe microvascular complications of diabetes mellitus and remains a leading cause of visual impairment and preventable blindness worldwide. It occurs in both Type 1 and Type 2 diabetes mellitus due to chronic hyperglycemia, which leads to structural and functional alterations in the retinal microvasculature (1). The condition develops gradually, progressing from non-proliferative stages to proliferative diabetic retinopathy (PDR), and may be complicated by Diabetic Macular Edema (DME)—a major cause of central vision loss in diabetic patients (1,2). Globally, diabetic retinopathy has emerged as a significant public health problem due to the escalating prevalence of diabetes mellitus. It is estimated that one in three people with diabetes has some degree of retinopathy, and approximately one in ten develops a vision-threatening form of the disease (2). According to the World Health Organization, diabetic retinopathy is responsible for about 4.8% of the 37 million cases of blindness globally (1). A comprehensive meta-analysis conducted by Yau et al. (2012) reported the global prevalence of any form of diabetic retinopathy to be 35.4%, with proliferative diabetic retinopathy (PDR) accounting for 7.2%, vision-threatening retinopathy for 11.7%, and diabetic macular edema (DME) for 7.4% (2).The Wisconsin Epidemiologic Study of Diabetic Retinopathy (W ESDR) further established that the prevalence of DME increases with the duration and severity of diabetes. In individuals with Type 2 diabetes mellitus, DME was present in 25% of those treated with insulin and 14% of those not on insulin therapy for 15 years (3). DME affects approximately 3% of eyes with mild non-proliferative diabetic retinopathy, 38% with moderate to severe NPDR, and 71% with proliferative diabetic retinopathy (PDR) (3). In the Indian context, the burden of diabetes and its ocular complications has shown a steep upward trend over the past two decades, paralleling the epidemiological transition in lifestyle and urbanization. India currently ranks among the countries with the largest number of people living with diabetes, with an estimated prevalence of 7.3%, ranging from 6.0% to 14.0% in different regions (4). Several population-based studies from South India have demonstrated a substantial prevalence of diabetic retinopathy. The Chennai Urban Rural Epidemiology Study (CURES) reported a prevalence of 34.1% among patients with Type 2 diabetes (5), while the Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SN-DREAMS) found a prevalence of 37% (6). A longitudinal cohort from South India estimated a four-year incidence of diabetic retinopathy at 9.2% and diabetic macular edema at 2.6% (7). The growing prevalence of DME is of particular concern in developing countries like India, where limited access to regular eye screening, poor glycemic control, and lack of awareness contribute to delayed diagnosis and irreversible vision loss. Early detection and timely intervention remain critical, as effective screening and treatment strategies can prevent up to 98% of severe visual loss associated with DR and DME (2,4). Understanding the anatomy of the macula is essential for comprehending the pathophysiology, clinical manifestations, and treatment modalities of diabetic macular edema. The macula, located at the posterior pole of the retina, is responsible for central vision and fine visual acuity. The unique structural features of the macula—such as its avascular foveal region, high density of cone photoreceptors, and specialized Müller cell arrangement—make it particularly vulnerable to metabolic and vascular insults seen in diabetes. The breakdown of the blood-retinal barrier, capillary leakage, and retinal thickening that characterize DME predominantly affect the macular region, leading to progressive visual deterioration (1,3). AIM To analyse and compare the outcomes of treatment in center involved diabetic macular edema based on mean average change in Best corrected visual acuity from baseline to month 1 through 6 months. PRIMARY OBJECTIVE 1. To determine the best modality of management with respect to mean average change in best corrected visual acuity from baseline. 2. To evaluate the time course of mean change in best corrected visual acuity from baseline. SECONDARY OBJECTIVE 1. To evaluate the effects of Anti VEGF on anatomical changes (central retinal subfield thickness) compared with grid laser. 2. Assessing the influence of comorbid conditions like hypertension, dyslipidemia and anaemia in resolution of macular edema and visual recovery.

STUDY DESIGN Prospective randomized single blinded clinical trial. SAMPLE SIZE CALCULATION n= (Z1-α/2+ Z1-β)2 * 2*σ2/d2, power of the study is 90% Where z1-β=1.28. Z1-α/2=1.96 (desired level of statistical significance) standard deviation of outcome variable N=2*(6.02)2(1.96+1.28)2÷(4.5)2=37 in each group. In my study i am taking a sample of size of 90 with 45 eyes in each group. STATISTICAL METHODS The collected data were analysed with IBM, SPSS statistics software 23.0 version. To describe about the data descriptive statistics frequency analysis, were used for categorical variables and the mean & S.D were used for continuous variables. To find the significant difference the bivariate samples in paired groups the paired sample t-test was used & for independent groups the unpaired sample t-test was used. In both the above statistical tools the proability value 0.05 is considered as significant level. INCLUSION CRITERIA 1. Age of either sex ≥ 18years 2. Patients with type 1 or 2 diabetes. 3. Patients newly diagnosed with “center involved” Diabetic macular oedema presenting to our outpatient department. EXCLUSION CRITERIA 1. Macular Edema due to other causes like BRVO, CRVO, Chronic Uveitis. 2. Visually significant cataract. 3. Antenatal mothers with GDM. 4. Already treated patients with diabetic macular edema. 5. Active intraocular inflammation/ infection in either eye METHODOLOGY 1. Patient presenting to Vitreo Retina services will be registered, evaluated and followed up during the study period. 2. A detailed history of the patient will be taken. Complete general examination with vitals measurement will be performed. Examination of RS, CVS, CNS will be performed. 3. Ocular examination including best corrected visual acuity (using ETDRS chart), anterior segment examination using Slit lamp, Fundus examination using Direct Ophthalmoscopy, slit lamp bio microscopy with 90D and indirect ophthalmoscopy with 20D will be done. Intraocular pressure (Goldmann applanation tonometry) will be measured. 4. Fundus fluorescein angiography, Optical Coherence Tomography will be done. Investigations such as Blood Pressure, Fasting Blood Sugar, Post Prandial Blood Sugar, Hba1c, lipid profile, serum urea and creatinine are done. 5. After investigating thoroughly, the patients with diabetic macular oedema are randomly subjected to injection anti VEGF for 45 eyes & macular grid lasers for 45eyes and followed up for assessing post treatment parameters

I. AGE INCIDENCE S No Years No of patients Percent 1 40 yrs 3 5.8 2 41 - 50 yrs 19 36.5 3 51 - 60 yrs 18 34.6 4 61 - 70 yrs 8 15.4 5 Above 70 yrs 4 7.7 Total 52 100.0 In our study the predominant age group affected is the 41 – 50 years was 36.5% followed by 51 – 60 years range 34.6% and 61-70years was 15.4% II. SEX INCIDENCE S NO Gender No of patients Percent 1 F 19 36.5 2 M 33 63.5 Total 52 100.0 The ratio of male to female in our study was 1.74:1 which correlated with WISCONSIN epidemiological study of diabetic retinopathy (1984) which showed male, female ratio was 1.5:1 III. TYPE OF DIABETES S No Type No of patients Percent 1 Type I 6 11.5 2 Type II 46 88.5 Total 52 100.0 In our study Type II diabetes is present in 88.5% of patients in which 61.4 % had NPDR and 11.5 % of patients had type I diabetes in which all patients had PDR. IV. DURATION OF DIABETES S. NO Years No of patients Percent 1 < 1 yr 2 3.8 2 1 - 5 yrs 6 11.5 3 6 - 10 yrs 19 36.5 4 Above 10 yrs 25 48.2 Total 52 100.0 In our study 15.3% had diabetes of <5 yrs and 48.2% had more than 10yrs of diabetes. This correlates with WISCONSIN Epidemiological study of diabetic retinopathy which showed 24% of patients have diabetes of 5 years or less duration had feature of diabetic maculopathy and 57.5% of patients have diabetes of 10 years and more duration of diabetes showed features of diabetic maculopathy V. SYSTEMIC DISEASE HT Dyslipidemia DN CAD No of patients 30 11 8 7 Percent 57.5 21.2 15.4 13.5 In our study 57.5 % had systemic hypertension, 21.2 % had dyslipidemia , 13.5 % had Cardiovascular disease and 15.4 % had Diabetic Nephropathy. VI. SEVERITY OF DIABETIC RETINOPATHY No of EYES Percent Mild NPDR 2 3.8 Moderate NPDR 9 17.3 Severe NPDR 17 32.6 Very Severe NPDR 4 7.7 Early PDR 11 21.2 HR PDR 9 17.3 Total 52 100.0 In our study 3.8% of patients had mild NPDR, 17.3% had moderate NPDR, 40.3% had severe to very severe NPDR and 38.5% of patients had PDR. VII. SYSTOLIC BLOOD PRESSURE SBP Treatment Number of patients Mean SD t-value p-value Baseline Grid Laser 25 128.8 21.1 0.967 0.338 # Anti VEGF 27 134.4 21.0 1 Month Grid Laser 25 128.0 14.4 0.840 0.405 # Anti VEGF 27 131.5 15.4 2 Months Grid Laser 25 126.0 17.6 1.047 0.300 # Anti VEGF 27 131.1 17.6 4 Months Grid Laser 25 126.0 14.7 0.938 0.353 # Anti VEGF 27 130.0 15.9 6 Months Grid Laser 25 124.4 15.3 0.400 0.691 # Anti VEGF 27 125.9 12.2 # No Statistical Significance at p > 0.05 level At baseline ,the mean systolic BP was 128.8 ± 21.1mmHg in the grid laser group and 134.4±21.0 mmHg in the Anti VEGF Group (p>0.05) and at 6mths, the mean was 124.4±15.3mmHg in the grid laser group and 125.9±12.2mmHg(p>0.05) in the antiVEGF group. There was no statistically significant difference in the systolic blood pressure at baseline in the laser group and antiVEGF group and at the end of 6 months. VIII. DIASTOLIC BLOOD PRESSURE DBP Treatment Number of eyes Mean SD t-value p-value Baseline Grid Laser 25 80.8 7.6 0.321 0.750 # Anti VEGF 27 81.5 7.7 1 Month Grid Laser 25 80.4 6.8 0.631 0.527 # Anti VEGF 27 79.3 6.2 2 Months Grid Laser 25 78.8 6.7 1.043 0.302 # Anti VEGF 27 80.7 6.8 4 Months Grid Laser 25 78.8 6.7 0.626 0.534 # Anti VEGF 27 77.8 5.1 6 Months Grid Laser 25 78.0 5.0 0.119 0.906 # Anti VEGF 27 78.1 4.0 # No Statistical Significance at p > 0.05 level At baseline ,the mean diastolic BP was 80.8 ± 7.6mmHg in the grid laser group and 81.5±7.7 mmHg in the Anti VEGF Group (p>0.05) and at 6mths, the mean was 78.0±5.0mmHg in the grid laser group and 78.1±4.0mmHg(p>0.05) in the antiVEGF group. There was no statistically significant difference in the diastolic blood pressure at baseline in the laser group and antiVEGF group and at the end of 6 months. IX. HbA1C HbA1c Treatment Number of patients Mean SD t-value p-value Baseline Grid Laser 25 7.3 0.5 0.396 0.694 # Anti VEGF 27 7.4 0.4 6 Months Grid Laser 25 7.2 0.5 0.164 0.870 # Anti VEGF 27 7.2 0.4 # No Statistical Significance at p > 0.05 level In our study the mean HbA1c was 7.3 ±0.5% in the grid laser group and in the antiVEGF group, the mean was 7.4 ±0.4% at baseline which is higher than normal. (p>0.396). At 6 months , the mean was 7.2 ± 0.5% and 7.2±0.4 %in the laser group and antiVEGF group respectively(p>0.05) X. SERUM TRIGLYCERIDE S. Triglyceride Treatment Number of patients Mean SD t-value p-value Baseline Grid Laser 25 136.3 28.8 0.094 0.926 # Anti VEGF 27 135.7 17.6 6 Months Grid Laser 25 127.3 17.4 0.189 0.851 # Anti VEGF 27 128.1 14.2 # No Statistical Significance at p > 0.05 level In the laser group, the mean of serum triglyceride was 136.3 ± 28.8mg/dl and 127.3± 17.4 mg/dl and in the anti VEGF group, the mean was135.7 ± 17.6 mg/dl and 128.1± 14.2 mg/dl at baseline and at 6 months respectively (p>0.05) with no statistically significant difference between the two groups Elevated levels of plasma triglycerides were associated with a greater risk of developing high risk PDR in the ETDRS. XI. TOTAL CHOLESTEROL T.Cholesterol Treatment Number of patients Mean SD t-value p-value Baseline Grid Laser 25 184.0 43.2 0.033 0.974 # Anti VEGF 27 184.3 29.2 6 Months Grid Laser 25 159.8 37.6 0.356 0.724 # Anti VEGF 27 163.1 30.1 # No Statistical Significance at p > 0.05 level At baseline, the mean was 184±43.2mg/dl in the grid laser group and 184.3±29.2mg/dl in the antiVEGF group(p>0.05) and at 6 months, it was 159.8±37.6 mg/dl and 163.1±30.1mg/dl in the laser and antiVEGF groups respectively(p>0.05).No significant difference found between the two groups at baseline and at the end of 6 months. EFFICACY OUTCOME MEASURES IN THE TWO TREATMENT GROUPS XII. MEAN CHANGE IN THE ETDRS BCVA ETDRS LS Treatment Number of eyes Mean SD t-value p-value Baseline Grid Laser 37 38.4 11.2 1.171 0.246 # Anti VEGF 39 35.6 9.5 1 Month Grid Laser 37 38.5 11.2 0.128 0.898 # Anti VEGF 39 38.2 9.5 2 Months Grid Laser 37 38.6 11.4 0.956 0.342 # Anti VEGF 39 40.9 9.6 4 Months Grid Laser 37 38.9 11.6 1.678 0.98 # Anti VEGF 39 43.0 9.7 6 Months Grid Laser 37 38.9 12.2 2.242 0.028 * Anti VEGF 39 44.6 9.7 # No Statistical Significance at p > 0.05,* Significant at p < 0.015 At baseline mean ETDRS BCVA in the laser group was 38.4 ± 11.2 and in the antiVEGF group was 35.6 ± 9.5 letter score(p>0.05). At 6 months mean ETDRS BCVA in the laser group was 38.9 ± 12.2 and in the antiVEGF group was 44.6 ± 9.7 (p<0.015) which shows a statistically significant difference between the two groups The mean change in the BCVA between baseline and 2 months in anti VEGF group was 5.3 letters and in the laser group, visual stabilization with no improvement of ETDRS letters was seen. The mean change in the BCVA between baseline and 4 months in anti VEGF group was 7.4 letters and in the laser group 0.5 letters was seen. The mean gain in BCVA was 9.0 letters in the anti VEGF group which is superior to the grid laser group which showed 0.5 letters from baseline to 6 months. This is highly statistically significant with p<0.01. Anti VEGF N Mean SD F-value p-value Baseline 39 35.6 9.5 509.84 0.0005 ** 2 Months 39 40.9 9.6 4 Months 39 43.0 9.7 6 Months 39 44.6 9.7 ** Highly Statistical Significance at p < 0.01 level The mean change in the BCVA between baseline and 2 months in anti VEGF group was 5.3 letters and 4 months was 7.4 letters. The mean gain in BCVA was 9.0 letters in the anti VEGF group at the end of 6 months, which is highly statistically significant with p<0.01. Grid Laser N Mean SD F-value p-value Baseline 37 38.4 11.2 3.911 0.030 * 2 Months 37 38.6 11.4 4 Months 37 38.9 11.6 6 Months 37 38.9 12.2 * Statistical Significance at p < 0.05 level In the laser group the mean change in the BCVA between baseline and 2 months was only visual stabilization with no improvement of ETDRS letters was seen. The mean change in the BCVA between baseline and 4 months and at the end of 6 months was only 0.5 letters. XIII. IMPROVEMENT OF VISUAL ACUITY Treatment ꭓ 2 – value p-value Grid Laser Anti VEGF A gain of < 5 EDTRS letters 70.3% (25) 2.6%(1) 68.236 0.0005 ** A gain of <10 ETDRS letters 2.7%(1) 48.7%(19) A gain of ≥ 10 ETDRS letters 0%(0) 48.7%(19) ** Highly Statistical Significance at p < 0.01 level An improvement of ≥ 2 lines of BCVA was seen in 19 eyes out of 39 eyes (48.7%) and an improvement of < 2 lines of BCVA was seen in 20 eyes out of 39 eyes (51.3%) in the Anti VEGF group Visual stabilization is seen in laser group at the end of 4 months and 6 months with an improvement of < 5 ETDRS letters in 26 eyes(73%) out of 37 eyes. A statistically significant difference was noted between two groups p<0.01 at the end of 6 month XIV. VISUAL STABILIZATION Treatment ꭓ 2 – value p-value Grid Laser Anti VEGF No loss of ETDRS letters 26 39 13.557 0.0005** 70.3% 100.0% Loss of ETDRS Letters 11 0 29.7% 0.0% ** Highly Statistical Significance at p < 0.01 level AntiVEGF group showed no loss of ETDRS letters from baseline during the follow up period of 6 months whereas in the laser group 11 eyes (29.7%) out of 37 eyes showed loss of ETDRS letters (p<0.01) which is statistically significant. XV. ANATOMICAL OUTCOME MEASURES OCT-CFT Treatment N Mean SD t-value p-value Baseline Grid Laser 37 584.6 115.3 1.460 0.149 # Anti VEGF 39 619.1 89.5 1 Month Grid Laser 37 551.5 116.0 0.291 0.772 # Anti VEGF 39 558.4 85.7 2 Months Grid Laser 37 521.1 116.2 0.488 0.627 # Anti VEGF 39 509.7 84.4 4 Months Grid Laser 37 495.9 121.0 0.715 0.477 # Anti VEGF 39 478.7 84.6 6 Months Grid Laser 37 473.6 123.2 0.856 0.396 # Anti VEGF 39 452.8 83.3 # No Statistical Significance at p > 0.05 In the laser group, mean central foveal thickness, as determined by OCT was 584.6±115.3 µm at baseline which decreased by 64 µm (±116.2µm)at month 2. At 4 months, mean central foveal thickness decreased by 88.7 µm (± 121.0 µm). At 6 months the mean central foveal thickness decreased by 111.0 µm (± 123.2 µm) from baseline. In the Anti VEGF group, mean central foveal thickness was 619.1±89.5 µm at baseline which decreased by 60 µm (± 85.7 µm) at month 1. At 2 months,it decreased by 110 µm (±84.4 µm). which is more than the laser group. At month 4, the central foveal thickness decreased by 140 µm (± 84.6 µm).and At the end of 6 month ,the mean central foveal thickness decreased by 165 µm. (± 83.3 µm) which is not statistically significant than the laser group (P<0.05) In the Anti VEGF group, a reduction in the mean central foveal thickness was 73% of macular edema from baseline. This improvement in mean central foveal thickness correlated well with the mean visual acuity The laser group showed a reduction of 81% at the end of 6 month from baseline but it is not accompanied by improvement in the mean visual acuity.

Diabetic Retinopathy (DR) and Diabetic Macular Edema (DME) are among the most significant microvascular complications of diabetes mellitus and constitute major causes of visual impairment in working-age adults worldwide. The present study emphasizes the anatomical basis of the macula and the mechanisms underlying diabetic maculopathy, correlating them with clinical and epidemiological data from previous literature. The findings of this study reaffirm that the duration of diabetes plays a critical role in the development and progression of DR and DME. The prevalence and severity of retinal microangiopathy increase with the duration of hyperglycemia, as reported in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), which demonstrated a higher 10-year incidence of DR with longer diabetes duration (8). In insulin-dependent diabetes mellitus, retinopathy rarely appears within the first five years after diagnosis, whereas in non-insulin-dependent diabetes, early retinal changes can develop even within this period (9). Age is another important determinant. The WESDR study observed that no children under 13 years with Type 1 diabetes had proliferative diabetic retinopathy (PDR) during a four-year follow-up, whereas risk increased substantially after puberty due to hormonal and metabolic changes (10). Pregnancy has also been associated with accelerated progression of DR, particularly among women with pre-existing retinopathy or pre-eclampsia (11). These findings suggest that hormonal and hemodynamic factors can influence microvascular integrity during pregnancy in diabetics. Glycemic control remains the cornerstone of preventing diabetic retinal complications. Persistent hyperglycemia has been shown to trigger biochemical pathways that promote retinal ischemia and vascular leakage. Several landmark trials have demonstrated that maintaining lower glycated hemoglobin (HbA1c) levels significantly reduces the risk of developing or worsening DME. The Diabetes Control and Complications Trial (DCCT) and the UK Prospective Diabetes Study (UKPDS) collectively established that intensive glycaemic control leads to nearly a 50% reduction in the incidence of macular oedema and retinopathy progression (12,13). Hypertension has a synergistic effect with hyperglycaemia in aggravating retinal damage. Elevated systolic and diastolic pressures increase capillary hydrostatic pressure, promoting endothelial dysfunction and vascular leakage in the macula. For every 10 mmHg decrease in mean systolic blood pressure, a 13% reduction in microvascular complications was observed in the UKPDS (14). Similarly, the WESDR noted that a 10 mmHg rise in diastolic pressure increased the four-year risk of macular edema by 330% in Type 1 and by 210% in Type 2 diabetes (8). Dyslipidaemia is another modifiable factor contributing to the formation of hard exudates and lipid deposition in the macula. The Early Treatment Diabetic Retinopathy Study (ETDRS) identified a strong association between elevated serum cholesterol and the presence of retinal hard exudates, suggesting that lipid-lowering therapy may play a preventive role in DME progression (15). Similarly, renal dysfunction and proteinuria are independent risk factors, indicating that microvascular damage is systemic in nature, affecting both renal and retinal microcirculations (16). In the Indian context, studies have consistently demonstrated that poor glycaemic control, prolonged duration of diabetes, and coexisting hypertension are the main drivers of DME development. Socio-economic and healthcare access barriers further compound this issue, leading to delayed diagnosis and treatment. Hence, multidisciplinary care—including strict metabolic control, regular ophthalmic screening, and public health interventions—is essential to mitigate the burden of visual disability. Furthermore, advances in ocular imaging such as Optical Coherence Tomography (OCT) and Fluorescein Angiography have revolutionized the understanding of macular changes in diabetic eyes. OCT allows early detection of retinal thickening, cystoid spaces, and serous detachments, providing objective quantification for treatment planning. The introduction of anti-VEGF therapy has significantly improved visual prognosis in DME, supplementing traditional laser photocoagulation by directly targeting vascular permeability mediators (15,16).

Diabetic Retinopathy and Diabetic Macular Edema are major causes of preventable blindness among individuals with long-standing diabetes. Good glycemic and blood pressure control significantly reduce the risk of visual loss. Understanding the anatomy of the macula is vital for detecting early pathological changes and guiding management. Modern imaging and targeted therapies, such as anti-VEGF agents, have improved outcomes. Early screening and multidisciplinary management remain essential to prevent irreversible vision impairment.

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