The influence of background diabetic retinopathy in the second eye on rates of progression of diabetic retinopathy between 2005 and 2010

Abstract PURPOSE: The Gloucestershire Diabetic Eye Screening Programme offers annual digital photographic screening for diabetic retinopathy to a countywide population of people with diabetes. This study was designed to investigate progression of diabetic retinopathy in this programme of the English NHS Diabetic Eye Screening Programme. METHODS: Mydriatic digital retinal photographs of people with diabetes screened on at least 2 occasions between 2005 and 2010 were graded and included in this study if the classification at first screening was no DR (R0), background DR in one (R1a) or both eyes (R1b). Times to detection of referable diabetic retinopathy (RDR) comprising maculopathy (M1), preproliferative (R2) or proliferative retinopathy (R3) were analysed using survival models. RESULTS: Data were available on 19 044 patients, 56% men, age at screening 66 (57-74) years (median, 25th, 75th centile). A total of 8.3% of those with R1a and 28.2% of those with R1b progressed to any RDR, hazard ratios 2.9 [2.5-3.3] and 11.3 [10.0-12.8]. Similarly 7.1% and 0.11% of those with R1a progressed to M1 and R3, hazard ratios 2.7 [2.3-3.2] and 1.6 [0.5-5.0], compared to 21.8% and 1.07% of those with R1b, hazard ratio 9.1 [7.8-10.4] and 15.0 [7.1-31.5]. CONCLUSIONS: The risk of progression is significantly higher for those with background DR in both eyes than those with background retinopathy in only one or in neither eye

Functional and structural findings of neurodegeneration in early stages of diabetic retinopathy:cross-sectional analyses of baseline data of the EUROCONDOR project

Cross-sectional study evaluating the relationship between: a) functional and structural measurements of neurodegeneration in initial stages of diabetic retinopathy (DR); and b) presence of neurodegeneration and early microvascular impairment. We analyzed baseline data of patients with type 2 diabetes (n=449) enrolled in the EUROCONDOR study (NCT01726075). Functional studies by multifocal ERG (mfERG) evaluated neurodysfunction and structural measurements using spectral domain optical-coherence tomography (SD-OCT) evaluated neurodegeneration. The mfERG P1 amplitude was more sensitive than the P1 implicit time (IT), and was lower in patients with ETDRS 20-35 than in patients with ETDRS <20 (p=0.005). In 58% of cases, mfERG abnormalities were present in the absence of visible retinopathy. Correspondence between SD-OCT thinning and mfERG abnormalities was shown in 67% of the eyes with ETDRS <20 and in 83% of the eyes with ETDRS 20-35. Notably, 32% of patients with ETDRS 20-35 presented no abnormalities in mfERG or SD-OCT. We conclude that there is a link between mfERG and SD-OCT measurements which increases with the presence of microvascular impairment. However, in our particular study population (ETDRS ≤ 35) a significant proportion of patients had normal GC-IPL thickness and normal mfERG findings. We raise the hypothesis that neurodegeneration may play a role in the pathogenesis of DR in many, but not in all type 2 diabetic patients

Effects of Topically Administered Neuroprotective Drugs in Early Stages of Diabetic Retinopathy:Results of the EUROCONDOR Clinical Trial

The primary objective of this study was to assess whether the topical administration of two neuroprotective drugs (brimonidine and somatostatin) could prevent or arrest retinal neurodysfunction in patients with type 2 diabetes. For this purpose, adults aged between 45 and 75 years with a diabetes duration ≥5 years and an Early Treatment of Diabetic Retinopathy Study (ETDRS) level of ≤35 were randomly assigned to one of three arms: placebo, somatostatin, or brimonidine. The primary outcome was the change in implicit time (IT) assessed by multifocal electroretinography between baseline and at the end of follow-up (96 weeks). There were 449 eligible patients allocated to brimonidine (n = 152), somatostatin (n = 145), or placebo (n = 152). When the primary end point was evaluated in the whole population, we did not find any neuroprotective effect of brimonidine or somatostatin. However, in the subset of patients (34.7%) with preexisting retinal neurodysfunction, IT worsened in the placebo group (P < 0.001) but remained unchanged in the brimonidine and somatostatin groups. In conclusion, the topical administration of the selected neuroprotective agents appears useful in preventing the worsening of preexisting retinal neurodysfunction. This finding points to screening retinal neurodysfunction as a critical issue to identify a subset of patients in whom neuroprotective treatment might be of benefit

Other retinal conditions in diabetes

Systemic hypertension is all too frequently co‐existent with diabetes mellitus, meaning that it is often difficult or impossible to clearly differentiate which is the cause of a particular retinal lesion. Hypertensive retinopathy shares several common lesions with diabetic retinopathy, principally retinal haemorrhage, cotton wool spots, hard exudates and apparent vascular occlusions. Microaneurysms, intraretinal microvascular abnormalities (IRMA) and venous beading are not, however, features commonly associated with hypertension. In older patients, central retinal vein occlusion (CRVO) is commonly associated with diabetes, hypertension and arteriosclerosis. CRVO is a severe or total outflow obstruction to the main vein leaving the eye. This occurs out of sight of the observer and happens within the confines of the retrobulbar region of the optic disc. Occlusion of the central artery requires the blockage to have occurred in the retrobulbar region of the eye, before bifurcation of the central artery as it enters the visible globe

Conditions with appearances similar to diabetic retinopathy

It is important to make a differential diagnosis between drusen and the presence of any retinal hard exudates which are diabetic in origin. One of the most frequently detected abnormal retinal features are drusen. The normal adult human eye possesses usually unobservable superficial retinal nerve fibres, connecting the photoreceptors ultimately to the visual cortex. Retinal nerve fibres, unlike those within the optic nerve itself, are usually devoid of a myelin sheath. On examination, myelinated nerve fibres (MNFs) can be seen as highly reflective whitish‐yellow opaque patches surrounding the optic disc with marked striations. The correct identification of patches of MNF is important in order to differentiate these from cotton wool spots, hard exudates and, in some cases, even retinal oedema. Coats' disease is an idiopathic retinal telangiectasia first described by the Scottish ophthalmologist George Coats in 1908

Screening for diabetic retinopathy: new perspectives and challenges

Although the prevalence of all stages of diabetic retinopathy has been declining since 1980 in populations with improved diabetes control, the crude prevalence of visual impairment and blindness caused by diabetic retinopathy worldwide increased between 1990 and 2015, largely because of the increasing prevalence of type 2 diabetes, particularly in low-income and middle-income countries. Screening for diabetic retinopathy is essential to detect referable cases that need timely full ophthalmic examination and treatment to avoid permanent visual loss. In the past few years, personalised screening intervals that take into account several risk factors have been proposed, with good cost-effectiveness ratios. However, resources for nationwide screening programmes are scarce in many countries. New technologies, such as scanning confocal ophthalmology with ultrawide field imaging and handheld mobile devices, teleophthalmology for remote grading, and artificial intelligence for automated detection and classification of diabetic retinopathy, are changing screening strategies and improving cost-effectiveness. Additionally, emerging evidence suggests that retinal imaging could be useful for identifying individuals at risk of cardiovascular disease or cognitive impairment, which could expand the role of diabetic retinopathy screening beyond the prevention of sight-threatening disease. Vujosevic S1, Aldington SJ2, Silva P3, Hernández C4, Scanlon P2, Peto T5, Simó R6

United kingdom prospective diabetes study, 30: Diabetic retinopathy at diagnosis of non-insulin-dependent diabetes mellitus and associated risk factors

Objectives: To report on the prevalence of retinopathy in patients with newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) and to evaluate the relationship of retinopathy to clinical and biochemical variables. Design: A multicenter, randomized, controlled clinical study of therapy in patients with NIDDM. Setting and Patients: Patients were part of the United Kingdom Prospective Diabetes Study, a 23-center study of 2964 white patients who had both eyes photographed and assessed. Outcome Measures: The presence and severity of diabetic retinopathy were evaluated by sex, and the relationship of retinopathy to medical and biochemical parameters was assessed. Results: Retinopathy, defined as microaneurysms or worse lesions in at least 1 eye, was present in 39% of men and 35% of women. Marked retinopathy with cotton wool spots or intraretinal microvascular abnormalities was present in 8% of men and 4% of women. The severity of retinopathy was related in both sexes to higher fasting plasma glucose levels, higher systolic and diastolic blood pressure, lower serum insulin levels, and reduced β-cell function. In addition, in men, increased alcohol consumption was related to increased severity of retinopathy, while leaner women had more severe eye lesions. Visual acuity was normal in most patients, but in men there was a trend for those with more severe retinal lesions to have worse visual acuity. Conclusions: Diabetic retinopathy is common in patients with newly diagnosed NIDDM. Careful ophthalmic assessment at diagnosis is important.</p

The Usefulness of Serum Biomarkers in the Early Stages of Diabetic Retinopathy: Results of the EUROCONDOR Clinical Trial

The main aim of this study was to evaluate the ability of serum biomarkers to predict the worsening of retinal neurodysfunction in subjects with type 2 diabetes. For this purpose, we measured selected molecules (N-epsilon-carboxy methyl lysine (CML), laminin P1 (Lam-P1), and asymmetric dimethylarginine (ADMA)) in the serum of 341 participants of the EUROCONDOR study at baseline, 24, and 48 weeks. Retinal neurodysfunction was assessed by measuring implicit time (IT) using multifocal electroretinography, and structural changes were examined by spectral domain-optical coherence tomography. The values of IT at baseline were directly correlated with baseline serum concentrations of CML (r = 0.135, p = 0.013). Furthermore, in the placebo group, increase in CML concentration throughout follow-up correlated with the IT (r = 0.20; p = 0.03). Baseline serum levels of CML also correlated with macular retinal thickness (RT) (r = 0.231; p < 0.001). Baseline Lam-P1 levels correlated with the increase of the RT at the end of follow-up in the placebo group (r = 0.22; p = 0.016). We provide evidence that CML may be a biomarker of both retinal neurodysfunction and RT, whereas Lam-P1 was associated with RT only. Therefore, circulating levels of these molecules could provide a complementary tool for monitoring the early changes of diabetic retinopathy (DR)