Advanced Proliferative Retinopathy Research Articles

A study of diabetic retinopathy in diabetic foot syndrome in Western Regional Institute of India

Background: Diabetes is a rapidly growing health challenge and potential epidemic across low-and-middle-income countries like India. Diabetic retinopathy (DR) is a consequence of diabetic microangiopathy, which may cause visual deterioration due to macular edema in any stage and vitreous hemorrhage or tractional retinal detachment in the advanced proliferative retinopathy stages. Aims and Objectives: The aim was to study the retinopathy status in diabetic patients with a risk of diabetic foot syndrome (DFS) visiting a western regional hospital in India. Materials and Methods: In this cross-sectional study, all patients with diabetes mellitus (DM) with a risk of DFS, visiting a tertiary care hospital during the study period, underwent an ophthalmological evaluation for documentation of their retinopathy status. Results: One hundred and fourteen patients diagnosed to have a risk profile for DFS were included in the study. Their mean age was 61.22 years and 81.6% were males. The mean duration of DM was 12.24 years, respectively. Of the 114 patients, 72 had DR. An increased presence of retinopathy in patients with an increased risk grade of diabetic foot (DF) was found significant by the Chi‐square test. (P<0.001). Conclusion: Our study found an increased presence of DR in Western Indian cohort with DFS. The severity of retinopathy was greater in patients with higher grades of risk for DF, therefore establishment of an association between DR and DFS will help in developing an integrated management strategy for these two grave consequences of diabetes.

Impact of Vitreal Tamponade on Functional Outcomes in Vitrectomy with ILM Peeling in Primary Macula-Involving Retinal Detachment: A Retrospective Analysis.

BackgroundTo compare visual outcomes of vitrectomy with internal limiting membrane (ILM) peeling and failed SF6 gas tamponade requiring silicone oil (SO) in a second procedure with primary SO tamponade in fovea-involving retinal detachment (FiRD).MethodsRetrospective analysis of 82 eyes with retinal detachment and mild, but without advanced proliferative retinopathy (PVR ≥C2) requiring vitrectomy for FiRD. Group 1 comprised 23 eyes that underwent SF6 tamponade resulting in re-detachment requiring revision surgery with secondary SO tamponade. Based on the intraoperative findings, group 2 patients had primarily received SO as vitreal tamponade (n=59). Patients receiving a scleral buckle surgery or with advanced PVR as well as patients with underlying vascular diseases and uveitis were excluded.ResultsPreoperative visual acuity (Early Treatment Diabetic Retinopathy Study letters) was 13.5 ± 19.1 in group 1 and 14.0 ± 18.3 in group 2 (p=0.44). Twelve months after first surgery for FiRD, visual acuity was 49.8 ± 19.8 in group 1 and 51.7 ± 18.7 letters in group 2 (p=0.63). Re-detachment after SO removal requiring revision surgery developed in 17.4 (n=4) and 15.3% (n=9) cases.ConclusionOur findings suggest that if retinal traction is completely relieved at the end of surgery, vitrectomy with ILM peeling and SF6 may, if successful, improve the functional outcomes in instances with visual potential, ie, a foveal detachment of short duration despite the presence of a mild to moderate PVR, but with the inherent increased risk of re-detachment requiring further intervention and the use of a SO tamponade. Hence, secondary SO installation during re-vitrectomy after failed primary reattachment surgery results in similar functional outcomes as primary oil filling.

Red blood cell distribution width and diabetes-associated complications

AimRed blood cell distribution width (RDW) is a marker of cardiovascular morbidity and mortality. However, there is little data on the relationship between RDW and diabetes-associated complications. The aim was to investigate whether there is any association between RDW, nephropathy, neuropathy and peripheral arterial disease (PAD) in a type 2 diabetic population. MethodsThis study included 196 diabetic patients with proliferative diabetic retinopathy. All subjects were investigated for diabetic nephropathy, diabetic neuropathy and PAD. Participants underwent 24-h blood pressure monitoring and were analysed for markers of the metabolic syndrome, inflammation, and insulin resistance. Results57% of the participants had diabetic nephropathy, 46% had diabetic neuropathy while 26% had PAD. No significant association was found between RDW, diabetic neuropathy and PAD (p=NS). However, RDW was strongly associated with diabetic nephropathy (p=0.006), even following adjustment for potential confounding variables. Multivariate logistic regression analysis showed RDW (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.15–2.35, p=0.006), estimated glomerular filtration rate (OR 0.98, 95% CI 0.96–0.99, p<0.001), night-time diastolic blood pressure (OR 1.07, 95% CI 1.03–1.11, p=0.001) and erythrocyte sedimentation rate (OR 1.03, 95% CI 1.004–1.05, p=0.019) to be independently associated with diabetic nephropathy. ConclusionsThis is the first study to report lack of association between RDW, neuropathy and PAD in subjects with type 2 diabetes mellitus. More importantly, RDW was shown to be significantly associated with diabetic nephropathy in a type 2 diabetic population with advanced proliferative retinopathy independent of traditional risk factors, including diabetes duration and glycaemic control.

Advanced proliferative diabetic retinopathy in four young patients with flexion contractures (Rosenbloom syndrome)

In this report, we present four patients with type 1 diabetes of long duration (more than 20 years) who had multiple joint contractures (Rosenbloom syndrome) and who presented with reduced vision and advanced proliferative diabetic retinopathy. All of the cases had short stature which was non-familial and all had other microvascular complications (nephropathy and neuropathy). It seems that limited joint mobility (LJM) is a risk factor not only for microvascular complications, but also for more severe and advanced proliferative retinopathy.

Elevated plasma CD105 and vitreous VEGF levels in diabetic retinopathy

Diabetic retinopathy is the leading cause of blindness in the industrialized world. Hyperglycaemia induces retinal hypoxia that upregulates a range of vasoactive factors which may lead to macular oedema and/or angiogenesis and hence potentially sight threatening retinopathy. In this study, we have focused on the association of CD105 and vascular endothelial growth factor (VEGF) with the development and progression of diabetic retinopathy by means of quantifying their expression in the plasma and vitreous of diabetic patients. CD105 levels were quantified in the plasma of 38 type I diabetic patients at various stages of retinopathy and 15 non-diabetic controls. In an additional cohort of 11 patients with advanced proliferative retinopathy and 23 control subjects, CD105 and VEGF were measured in the vitreous. The values were expressed as median (range) and statistical analysis was carried out using the non-parametric Mann-Whitney U test. Plasma CD105 levels were significantly increased in diabetic patients [1.8 (1.1-2.4) ng/ml] compared with non-diabetic controls [0.7 (0.3-1.8) ng/ml] (p<0.01). Plasma CD105 levels were elevated in diabetic patients with all stages of retinopathy, the highest level was observed in background retinopathy [2.3 (2.1-2.5) ng/ml] followed by proliferative retinopathy [2.1 (0.9-2.8) ng/ml] and advanced proliferative retinopathy [1.4 (0.6-1.8) ng/ml]. Vitreous contents of CD105 did not differ between controls and patients with advanced proliferative retinopathy, but vitreous levels of VEGF were elevated by approximately 3-fold in patients with advanced proliferative retinopathy [7.2 (1.90-15.60) ng/ml] compared with the control subjects [1.80 (1.10-2.210)] (p<0.01). These observations indicate that plasma levels of CD105 and vitreous levels of VEGF are associated with diabetic retinopathy, suggesting that CD105 and the angiogenic factor VEGF may play a critical role in the development and progression of diabetic retinopathy. Further studies are required to determine whether circulating CD105 levels could serve as a surrogate marker for early stage retinopathy and for monitoring disease progression.

Molecular imaging system for possible prediction of active retinopathy in patients with Diabetes mellitus

The deposition of advanced glycation end products is enhanced in Diabetes mellitus (DM) and has been linked to diabetic complications such as a microvascular disease. Glycated proteins have receptors on mononuclear blood cells (MBCs) and have been shown to generate reactive oxygen species altering gene expression and modifying cellular targets, such as endothelial cells. Retinal angiopathy is a frequently observed microvascular complication in DM-patients. Because of the central role of activated MBCs, we hypothesised a functional link between specific alterations in gene expression of MBCs, an increased activity of matrix proteases in serum, and the extent of retinal angiopathy in DM. An appearance and proliferation index of diabetic retinopathy was evaluated in 38 DM-patients using fluorescein angiography. Alterations of gene transcription levels in MBCs were investigated using hybridisation of individual mRNA-pools to Atlas Array with a concomitant quantification of specific cDNAs by "Real-Time"-PCR. The activity of matrix metalloproteinases MMP-2 and MMP-9 in individual serum samples was measured by zymography combined with densitometric imaging system. Hybridisation to Atlas Array of mRNA-pools isolated from MBCs revealed an enhanced expression of recoverin in DM-patients compared to the control group. "Real-Time"-PCR showed the highest recoverin levels in the DM-subgroup with a high proliferation index. MMP-2 activity was highly increased in 36% of all patients, and in 44, 44, and 19% of patients with proliferative retinopathy, advanced proliferative retinopathy, and no detectable proliferation respectively. In those 3 groups MMP-9 activity was highly increased in 56, 67, and 31% of patients respectively, and in 44% of all DM-patients. In contrast to patients with active proliferation, the simultaneous high activation of all three genes was not observed in patients without active proliferation. The ex vivo molecular imaging system developed in this work may be helpful for the prediction of active proliferative retinopathy in DM.

Advanced Proliferative Retinopathy and Iris Neovascularization in an Intravenous Drug Abuser

Advanced Proliferative Retinopathy and Iris Neovascularization in an Intravenous Drug Abuser

Ophthalmological follow-up of Type 1 (insulin-dependent) diabetic patients after kidney and pancreas transplantation

We studied the effect of successful kidney and pancreas transplantation on visual function and diabetic retinopathy in 18 patients with long-term Type 1 (insulin-dependent) diabetes mellitus (17 to 38 years) and with advanced proliferative retinopathy. The average age of the patients was 42 years. Prior to transplantation, 5 eyes were in end-stage ophthalmic complication due to neovascular glaucoma. An ophthalmological follow-up was performed between 1-6 years post-surgery. Analysis of the results showed that the diabetic retinopathy had stabilized after transplantation in 12 cases (66%) with a supplementary photocoagulation in the majority of cases. The proliferation continued in 4 patients (22%) leading to blindness in 2 patients and recurrence of vitreous haemorrhages despite the photocoagulation in the other 2 cases. An improvement was observed on fluorescein angiography in a patient with pre-papillar glial proliferation without photocoagulation. Ten patients were reported to have a cataract and were operated on in two cases before transplantation; in one patient, the cataract increased following transplantation. In conclusion, the kidney and pancreas transplantation was not effective in our patients in reversing the clinical and angiographic signs of diabetic retinopathy. Moreover, a worsening of the lesions was observed in some cases; this was probably due to the irreversible microangiopathic lesions due to advanced evolution of diabetes.

Progression of diabetic retinopathy after pancreas transplantation for insulin-dependent diabetes mellitus.

We studied the effect of successful pancreas transplantation and consequent normoglycemia (mean total hemoglobin A1, 7.0 percent; range, 5.8 to 8.3) on visual function and diabetic retinopathy in 22 patients with Type I diabetes mellitus (study group). Sixteen similar patients in whom pancreas transplantation had been unsuccessful (mean total hemoglobin A1, 12.0 percent; range, 8.0 to 18.0) served as a control group. The majority of patients in both groups had advanced proliferative retinopathy. At a mean follow-up of 24 months we found no significant difference between the groups in the rate of progression of retinopathy, expressed as a score. Success of the transplantation did not prevent progression of retinopathy across the range of retinopathy studied. Progressive retinopathy was observed more commonly in patients with low retinopathy scores (nonproliferative or mild proliferative retinopathy) at base line in both the study group (13 of 17 eyes, or 76 percent) and the control group (7 of 12 eyes, or 58 percent). Further analysis suggested the possibility that after three years of euglycemia, the study group had less deterioration than the control group, particularly in eyes with advanced retinopathy. We observed no difference in the rate of loss of vision between the two groups. This study provides evidence that pancreas transplantation and subsequent normoglycemia neither reverse nor prevent the progression of diabetic retinopathy.

Clinical arrangement of classification of diabetic retinopathy.

A new classification for diabetic retinopathy was presented and modified from Scott's classification which was most commonly used in Japan. Diabetic retinopathy was divided into benign and malignant retinopathy, and the former was named type A and the latter type B. Type A included background retinopathy and the interrupted stage of proliferative retinopathy. Background retinopathy was divided into two groups (AI, and AII). Interrupted proliferative retinopathy was also divided into three groups (AIII, IV, and V). Type B included preproliferative retinopathy, advanced proliferative retinopathy and the final stage of proliferative retinopathy. Preproliferative retinopathy was labeled Stage BI and advanced proliferative retinopathy was divided into two groups (BII and BIII). The final stage of proliferative diabetic retinopathy was divided into three stages (BIV, BV and VI). This new classification also presents the therapeutic method to be employed at each stage of diabetic retinopathy.

Proliferative diabetic retinopathy at the time of diabetes diagnosis

The diagnosis of proliferative retinopathy led to a search for a hitherto undiagnosed diabetes mellitus in 5 patients. In 3 further patients advanced proliferative retinopathy was found only a few months after diagnosis of diabetes. In all 8 patients it was possible to regulate the diabetes with oral medication. The mean age of the patients was 49.1 years, the youngest being 42, the oldest 54. The question as to whether the courses of proliferative retinopathy and diabetes mellitus may be heterogeneous is discussed.