Prevalence of Diabetic Retinopathy in Urban Slums: The Aditya Jyot Diabetic Retinopathy in Urban Mumbai Slums Study—Report 2

Objectives: The aims of the study were to estimate the prevalence of diabetic retinopathy (DR) and enumerate history-based risk factors in the urban slums of Western India.

Methods: The population-based study was conducted in seven wards of Mumbai urban slums, where we screened 6569 subjects of ≥ 40 years age, with a response rate of 98.4%, for type 2 diabetes mellitus (T2DM) based on American Diabetes Association criteria. All subjects with T2DM underwent dilated 30° seven-field stereo-fundus-photography for DR severity grading based on modified Airlie House classification. A multivariate logistic regression model was used to assess the correlation of DR with the history-based risk factors.

Results: The prevalence of DR in the general population of Mumbai urban slums was 1.41% (95% CI 0.59–2.23) and in the T2DM population it was 15.37% (95% CI 8.87–21.87). The positive associations with DR were the longer duration of DM (≥ 11 years: OR, 12.77; 95% CI 2.93–55.61) and male gender (OR, 2.05; 95% CI 1.08–3.89); increasing severity of retinopathy was also significantly associated with longer duration of DM (p < 0.001). However, history of hypertension, family history of DM, consanguineous marriage and migration status were not associated with DR in the study population.

Conclusions: The prevalence of DR in the general population and T2DM subjects were 1.41% and 15.37% respectively in Mumbai urban slums. Duration of DM and male gender were significantly associated with DR. The slums in Western India show the trends of urban lifestyle influences similar to the rest of urban India.     

Foveal slope measurements in diabetic retinopathy: Can it predict development of sight-threatening retinopathy? Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SN-DREAMS II,Report no 8)

Aim:

The aim was to assess the foveal slope configuration in subjects with type 2 diabetes in a population-based study.

Materials and Methods:

A subset of 668 subjects from Sankara Nethralaya Diabetic Retinopathy (DR) Epidemiology and Molecular Genetics Study II, a population-based study, were included in the current study. All the subjects underwent comprehensive ophthalmic evaluation including spectral domain optical coherence tomography. Foveal thickness was assessed in five central early treatment DR study quadrants from the three-dimensional scan and foveal slope was calculated in all the four quadrants.

Results:

Subjects with sight-threatening DR (STDR) had significantly shallow foveal slope in inferior quadrant (STDR: 7.33 ± 6.26 vs. controls: 10.31 ± 3.44; P = 0.021) when compared to controls and in superior (STDR: 7.62 ± 5.81 vs. no DR: 9.11 ± 2.82; P = 0.033), inferior (STDR: 7.33 ± 6.26 vs. no DR: 8.81 ± 2.81; P = 0.048), and temporal quadrants (STDR: 6.69 ± 5.70 vs. no DR: 7.97 ± 2.33; P = 0.030) when compared to subjects with no DR. Foveal slope was significantly shallow among the older age groups in subjects with no DR (P < 0.001) and non-STDR (P = 0.027). Average foveal slope in the diabetic subjects was independently and significantly correlated with increase in age (r = −0.241; P < 0.001) and central subfield thickness (r = −0.542; P < 0.001).

Conclusion:

Changes in foveal slope were seen with increasing age; however, in diabetes these segmental slope changes can be seen in late DR (STDR).     

Is there a correlation between the severity of diabetic retinopathy and keratoconjunctivitis sicca?

PURPOSE: Patients with diabetic retinopathy (DRP) seldom report symptoms of ocular surface irritation, but evaluations of dryness are pathologic. This study was designed to evaluate the correlation between the severity of DRP and dry eyes. METHODS: We included 144 eyes of 72 patients. Severity of retinopathy was graded according to the Early Treatment Diabetic Retinopathy Study. The examinations for dry eyes included Schirmer's test, break-up time, lipid layer thickness, fluorescein and rose bengal staining of the cornea, impression cytology, and a questionnaire. A sicca severity score was calculated using a point system of the results of these tests. Patients were divided into three groups: postpanretinal laser coagulation (PPL), postcentral laser coagulation (PCL), and those with no laser treatment (0-L). For statistics, we used the correlation coefficient to determine relationships and the unpaired Student t test for statistical difference. RESULTS: The correlation (c) of keratoconjunctivitis sicca (KCS) and DRP after laser treatment was c = 0.24 and after central laser treatment was c = 0.22; the correlation without laser treatment was 0.54. The best correlation is 1 or -1, the worst was 0. The score of those patients with mild to moderate retinopathy was compared to that of patients with severe to proliferative disease. There was a significant statistical difference in the sicca severity score between both groups, (p < 0.006. Student t test). CONCLUSION: KCS represents another manifestation of diabetes mellitus and its severity--measured by a many-membered score--correlates with the severity of the DRP.     

Is acetazolamide effective in the treatment of diabetic macular edema? A pilot study

Aim: To investigate whether acetazolamide, already found to be helpful in decreasing cystoid macular edema in patients with retinitis pigmentosa, was also effective in the treatment of diabetic macular edema in nonproliferative retinopathy. Methods:Two randomized age- and sex-matched groups (cases and controls) of 12 diabetics (five Type 1 and seven Type 2) were selected for this pilot study and graded for retinopathy (Early Treatment of Diabetic Retinopathy Study – Airlie House Classification). Cases were treated with acetazolamide for three months according to a standard protocol. The Early Treatment of Diabetic Retinopathy Study chart was used for assessing far-best corrected visual-acuity, and fluorescein angiography was performed using the Heidelberg Retina Angiograph. The Amsler grid-test and computerized-perimetry (Octopus 2000R) were also performed. Results: Fluorescein-angiographic findings and perimetric data improved significantly (p < 0.01) in the acetazolamide-treated cases compared to the controls while visual-acuity varied only slightly (p > 0.01). The Amsler grid-test resulted insignificant in our study (p > 0.05). No adverse effects or significant variations in laboratory tests were recorded. Conclusion: Further clinical investigations involving larger numbers of patients and a longer follow-up are required to confirm these preliminary results. However, the present study seems to suggest that acetazolamide could be effective in reducing fluorescein-angiographic findings and improving perimetric data in diabetics with macular edema, even though the mechanism of action remains obscure. Visual-acuity varied only slightly.     

Does myopia decrease the risk of diabetic retinopathy in both type-1 and type-2 diabetes mellitus?

Purpose:To study the relationship between the severity of myopia and the severity of diabetic retinopathy (DR) in individuals with type 1 or type 2 diabetes mellitus (DM).Methods:This retrospective study was conducted using data from electronic medical records from a multicentric eyecare network located in various geographic regions of India. Individuals with type 1 or type 2 DM were classified according to their refractive status. Severe nonproliferative DR (NPDR), PDR, or presence of clinically significant macular edema (CSME) with any type of DR was considered as vision-threatening diabetic retinopathy (VTDR).Results:A total of 472 individuals with type-1 DM (mean age 41 ± 10 years) and 9341 individuals with type-2 DM (52 ± 9 years) were enrolled. Individuals with a hyperopic refractive error had a significant positive association with the diagnosis of VTDR (odds ratio (OR) 1.26; 95%CI 1.04–1.51, P = 0.01) and moderate nonproliferative DR (OR 1.27; 95%CI 1.02–1.59, P = 0.03) in type-2 DM; however, no significant association was found in type-1 DM. After adjusting for age, gender, anisometropia, and duration of diabetes, the presence of high myopia (< - 6 D) reduced the risk of VTDR in type 2 DM (OR 0.18; 95% CI 0.04–0.77, P = 0.02), but no association was found in type 1 DM. Mild and moderate myopia had no significant association with any forms of DR in both type-1 and type-2 DM.Conclusion:Hyperopic refractive error was found to increase the risk of VTDR in persons with type 2 DM. High-myopic refractive error is protective for VTDR in type 2 DM, but not in type-1 DM.     

Lupus anticoagulant positivity in insulin dependent diabetic patients: an additional risk factor in the pathogenesis of diabetic retinopathy?

AIMS: To investigate whether lupus anticoagulant (LA) positivity, a marker of endothelial dysfunction, might be relevant to the pathogenesis of diabetic retinopathy (DR). METHODS: 32 IDDM patients were examined for LA, fibrinogen, prothrombin (PT), PTT, prothrombin degradation products (F1+2), and activated protein C (APC). RESULTS: APC decreased and F1+2 increased significantly in LA positive but not in LA negative patients; 60% of LA positive and 18% of LA negative subjects had DR. PT, PTT, and fibrinogen levels were insignificant. CONCLUSION: These preliminary findings suggest that LA positivity could represent an additional risk factor for DR, acting as a link between the immunological and haemostatic systems.     

Is serum cholesterol associated with progression of diabetic retinopathy or macular edema in persons with younger-onset diabetes of long duration?

PURPOSE: To quantitate the relationships of total cholesterol and high-density lipoprotein cholesterol to the incidence and progression of diabetic retinopathy and macular edema 5 years later in those with younger-onset diabetes of long duration. METHODS: Casual serum specimens for lipid values and fundus photography at the time of the lipid determinations were evaluated with regard to retinal lesions in photographs taken 5 years later during the course of a population-based cohort study. RESULTS: Univariable associations were significant for associations of incident retinal lesions with total cholesterol/high-density lipoprotein cholesterol, but multivariable associations considering covariates were not significant. CONCLUSION: Our data suggest that lowering cholesterol by therapeutic means may not be indicated for the sole purpose of decreasing the incidence or progression of these retinal lesions.     

Retinopathy in non diabetics,diabetic retinopathy and oxidative stress: a new phenotype in Central Africa?

AIM: To evaluate the rates of retinopathy without diabetes and diabetic retinopathy (DR), associated with some markers of oxidative stress, antioxidants and cardiometabolic risk factors.METHODS: We determined the prevalence of DR in 150 type 2 diabetes mellitus (T2DM) patients, that of retinopathy in 50 non diabetics, the levels of body mass index (BMI), waist circumference (WC), blood pressure, lipids, 8-isoprostane, 8-hydroxydeoxyguanosine (8-OHdG), gamma-glutamyl transferase GT (GGT), oxidized low-density lipoprotein (OxLDL), thiobarbituric acid reacting substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), uric acid, creatinine, albumin, total antioxidant status (TAOS), zinc, selenium, magnesium, vitamin C, vitamin D, vitamin E, glucose, apolipoprotein B (ApoB).RESULTS: The prevalences of DR at 53y and Rtp at 62y were 44% (n=66) and 10% (n=5), respectively. The highest levels of 8-isoprostane, 8-OHdG, TBARS, SOD, and OxLDL were in DR. The lowest levels of vitamin D, vitamin C, TAOS, and vitamin E were in DR. In the case-control study discriminant analysis, the levels of vitamin C, vitamin D, ApoB, 8-OHdG, creatinine, Zn, vitamin E, and WC distinguished significantly non-diabetics without DR (controls), T2DM patients without DR and T2DM patients with DR.CONCLUSION: Anticipation of DR onset is significantly associated with the exageration of oxidative stress biomarkers or decrease of antioxidants in African type 2 diabetics. Prevention of oxidative stress and abdominal obesity is needed. Supplementation in vitamin C, D, and E should be recommended as complement therapies of T2DM.     

Novel pharmacotherapies in diabetic retinopathy: Current status and what's in the horizon?

The blood–retinal barrier (BRB) alteration is the hallmark feature of diabetic retinopathy. Vascular endothelial growth factor (VEGF) is a potent vasopermeability factor that has been implicated in the pathogenesis of BRB alteration. Inflammation also plays a crucial role in this process with involvement of several chemokines and cytokines. Multiple anti-VEGF drugs are widely used as in the treatment of diabetic macular edema (DME) as well as proliferative diabetic retinopathy. Several clinical trials have proved the beneficial effects of these drugs in improvement of vision and prevention of vision loss. However, the response to anti-VEGF drugs in DME is not complete in a significant number of patients. The effect seems transient in this latter group, and many patients do not show complete resolution of fluid. Potential novel therapies targeting molecules beyond VEGF are being developed and examined in clinical trials.     

The relationship between insulin resistance/β-cell dysfunction and diabetic retinopathy in Chinese patients with type 2 diabetes mellitus: the Desheng Diabetic Eye Study

AIM: To investigate the relationship between insulin resistance (IR)/β-cell dysfunction and diabetic retinopathy (DR) in Chinese patients with type 2 diabetes mellitus (T2DM), and to explore further whether there were differences in the relationship among diabetic patients with higher and lower body mass index (BMI). METHODS: Cross-sectional study. A total of 1466 subjects with T2DM were recruited in a local Desheng Community of urban Beijing from November 2009 to June 2012 for the cohort of Beijing Desheng Diabetic Eye Study. Standardized evaluation was carried out for each participant, including questionnaire, ocular and anthropometric examinations, and laboratory tests. Seven fields 30° color fundus photographs were used for DR grading according to the Early Treatment Diabetic Retinopathy Study protocols. Homeostatis Model Assessment (HOMA) method was employed for IR and β-cell function assessment. RESULTS: After excluding those participants who were treated with insulin (n=352) or had missing data of fasting insulin (n=96), and further excluding those with poor quality of retinal photographs (n=10), a total of 1008 subjects were included for the final analysis, 406 (40.3%) were men and 602 (59.7%) were women, age ranging from 34 to 86 (64.87±8.28)y. Any DR (levels 14 and above) was present in 278 (27.6%) subjects. After adjusting for possible covariates, the presence of any DR did not correlate with HOMA IR [odds ratio (OR) 1.51, 95% confidence interval (CI) 0.87-2.61, P=0.14] or HOMA β-cell (OR 0.71, 95%CI 0.40-1.26, P=0.25). After stratification by BMI, the presence of any DR was associated positively with HOMA IR (OR 2.46, 95%CI: 1.18-5.12, P=0.016), and negatively with HOMA β-cell (OR 0.40, 95%CI: 0.19-0.87, P=0.021) in the group of patients with higher BMI (≥25 kg/m2). In the group of patients with lower BMI (<25 kg/m2), the presence of any DR was not associated with HOMA IR (OR 1.00, 95%CI: 0.43-2.33, P=1.00) or HOMA β-cell (OR 1.41, 95%CI: 0.60-3.32, P=0.43). CONCLUSION: The data suggest that higher IR and lower β-cell function are associated with the presence of DR in the subgroup of diabetic patients with higher BMI. However, this association is not statistically significant in diabetic patients with lower BMI.     

Does tight control of systemic factors help in the management of diabetic retinopathy?

Diabetic retinopathy (DR), one of the leading causes of preventable blindness, is associated with many systemic factors that contribute to the development and progression of this microvascular complication of diabetes. While the duration of diabetes is the major risk factor for the development of DR, the main modifiable systemic risk factors for development and progression of DR are hyperglycemia, hypertension, and dyslipidemia. This review article looks at the evidence that control of these systemic factors has significant benefits in delaying the onset and progression of DR.     

Is there a correlation between structural alterations and retinal sensitivity in morphological patterns of diabetic macular edema?

Spectral domain optical coherence tomography (SDOCT) enables enhanced visualization of retinal layers and delineation of structural alterations in diabetic macular edema (DME). Microperimetry (MP) is a new technique that allows fundus-related testing of local retinal sensitivity. Combination of these two techniques would enable a structure-function correlation with insights into pathomechanism of vision loss in DME. To correlate retinal structural derangement with retinal sensitivity alterations in cases with diabetic macular edema, using SDOCT and MP. Prospective study of 34 eyes of 30 patients with DME. All patients underwent comprehensive ophthalmic examination, fluorescein angiography, microperimetry and SDOCT. Four distinct morphological patterns of DME were identified- diffuse retinal thickening (DRT), cystoid macular edema (CME), schitic retinal thickening (SRT) and neourosensory detachment (NSD) of fovea. Some retinal loci presented with a mixture of above patterns There was significant difference in retinal thickness between groups (P<0.001). Focal retinal sensitivity measurement revealed relatively preserved retinal sensitivity in areas with DRT (13.8 dB), moderately reduced sensitivity (7.9 dB) in areas with CME, and gross retinal sensitivity loss in areas with SRT (1.2 dB) and NSD (4.7 dB) (P<0.001). Analysis of regional scotoma depth demonstrated similar pattern. Retinal sensitivity showed better correlation to OCT pattern (r=-0.68, P<0.001) than retinal thickness (r=-0.44, P<0.001). Structure-function correlation allows better understanding of the pathophysiology of visual loss in different morphological types of DME. Classification of macular edema into these categories has implications on the prognosis and predictive value of treatment.     

Do retinopathy signs in non-diabetic individuals predict the subsequent risk of diabetes?

BACKGROUND/AIMS: Isolated retinopathy signs are common in non-diabetic individuals and have been shown to be associated with impaired glucose metabolism. In a cohort of people without diabetes, the association of these retinopathy signs and subsequent development of diabetes were examined. METHODS: A population based cohort study of 7992 people aged 49-73 years without diabetes was conducted. Retinal photographs of these participants were evaluated for the presence of retinopathy signs according to a standardised protocol. Incident cases of diabetes were identified prospectively. RESULTS: After a follow up of 3 years, 291 (3.6%) people developed incident diabetes. In the total cohort, retinopathy was not significantly associated with incident diabetes (4.7% v 3.6%, multivariable adjusted odds ratio (OR) 1.1, 95% confidence intervals (CI), 0.7 to 1.9). However, among participants with a positive family history of diabetes, retinopathy was associated with incident diabetes (10.4% v 4.8%, multivariable adjusted OR 2.3, 95% CI, 1.0 to 5.3). Among participants without a family history of diabetes, retinopathy was not associated with incident diabetes CONCLUSIONS: In individuals with a family history of diabetes, retinopathy signs predict subsequent risk of clinical diabetes.