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Classification of severity of diabetic retinopathy Lesions presentSeverityNonproliferativeNo retinal lesionsNo retinopathyNo lesions other than microaneurysmsMicroaneurysms onlyMicroaneurysms plus retinal hemorrhage,hard exudateMild NPDR,venous loops,or bothMild NPDR plus cottonwool spots and/or IRMAModerate NPDRPresence of one of the following features:microaneurysms plus venous beading and/or H/MA Standard photograph 2A in four quadrants,or marked venous beading in two or more quadrants, or moderate IRMA(standard photograph 8A in one or more quadrants) Severe NPDRTwo or more of the above features described in severe NPDRVery severe NPDRProliferativeNew vessels and/or fibrous proliferations;or preretinal and/or vitreous hemorrhagePDR without HRCNVDstandard photograph 10A;or less extensive NVD,if vitreous or preretinal hemorrhage is present;or NVEhalf disc area,if vitreous or preretinal hemorrhage is presentPDR with HRCExtensive vitreous hemorrahage precluding grading,retinal detachment involving the macula,or phthisis bulbi or enucleation secondary to a complication of diabetic retinopathy Advanced PDR

SIMPLIFIED CLASSIFICATION OF DIABETIC RETINOPATHYln an attempt to improve communication between the ophthalmologists and the primary care physicians caring for patients with diabetes and between clinicians worldwide, a recent international classification of diabetic retinopathy and macular edema was developed. This classification is based on the data collected in the clinical trials and epidemiologic studies of diabetic retinopathy and it simplifies the ETDRS classification ofdiabetic retinopathy for clinical.With the introduction of this new simplified scale, it is hoped that these systems will be valuable in improving both screening of individuals with diabetes and communication and discussion among individuals caring for these patients.

EPIDEMIOLOGY OF DIABETES AND DIABETIC RETINOPATHYThe Centers for Disease Control estimate that 18.2 millionAmerican have diabetes and 5.2 million don't know they haveit . Type 2 diabetes accounts for up to 95% of aIl diabetes cases ,affecting 8% of the population aged 20 and older. Among the population 60 years and older, 18.6% are affected with diabetes . The prevalence of type 2 diabetes has tripled in the last 30 years , much of it due to an increase in obesity.

Among the estimated 10.2 million individuals in the USA older than 40 years of age and with known diabetes, the prevalence rates of diabetic retinopathy and vision-threatening diabetic retinopathy were 40.3% and 82%, respectively. This translates to 4.1 million adults over the age of 40 years having diabetic retinopathy; one in every 12 known persons with diabetes has severe visionthreatening diabetic retinopathy.

Data from population-based studies such as the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) provide valuable information regarding both the prevalence and the risk factors associated with the development of diabetic retinopathy.

ln the younger-onset group, which consists of patients whose age at diagnosis of diabetes was less than 30 years and who were taking insulin at the time of the examination (presumably those with type 1 diabetes), retinopathy, either proliferative or nonproliferative, was seen in 13% of patients with less than a 5-year duration of diabetes and in 90% of patients with a duration of 10 to 15 years.

PDR, the most vision-threatening form of the disease, is present in approximately 25% of patients with type 1 diabetes and a 15-year duration of the disease.

For patients with an onset of diabetes at 30 years of age or older (those with type 2 diabetes) and a duration of diabetes less than 5 years, 40% of those taking insulin and 24% of those not taking insulin have retinopathy.

These rates increase to 84% and 53%,respectively, with an increased diabetes duration of 15 to 19 years. PDR develops in 2% of patients with type 2 diabetes and a duration less than 5 years and 25% of patients with a duration of 25 or more years of diabetes.

The prevalence of diabetic macular edema did not vary as much by diabetes type. The prevalence of diabetic macular edema is approximately 18% to 20% in patients with either type 1 or type 2 (insulin-taking) diabetes.

RISK FACTORS FOR PROGRESSION OF RETINOPATHYSeverity of retinopathyAs retinopathy progresses from the mild to moderate to severe and then very severe stages, the risk of developing PDR or visualloss also increases.

ln the ETDRS, eyes with very severe NPDR or mild to moderate PDR, or both, had a 60-fold increased risk of developing high-risk PDR after 1 year of follow-up, compared with eyes with mild NPDR (48.5% versus 0.8%).

After 5 years of follow-up, there was still a fivefold increased risk (74.4% versus 14.3%).

For patients with bilateral moderate NPDR, the 4-year risk of progression to PDR was increased by 40-fold when compared with patients who had microaneurysms in only one eye.

Diabetic retinopathy disease severity scaleProposed disease severity levelFinding observable upon dilated ophthalmoscopyNo apparent retinopathyNo abnormalitiesMild nonproliferative diabetic retinopathyMicroaneurysms onlyModerate nonproliferative diabetic retinopathyMore than just microaneurysms but less than severe nonproliferative diabeticretinopathySevere nonproliferative diabetic retinopathyAny of the following: More than 20 intraretinal hemorrhages in each of four quadrantsDefinite venous beading in more than two quadrantsProminent intrartinal microvascular abnormalities in more than one quadrant and no signs of proliferative retinopathyProliferative diabetic retinopathyOne or more of the following:NeovascularizationVitreous/preretinal hemorrhageDiabetic macular edema disease severity scaleProposed disease severity levelFinding observable upon dilated ophthalmoscopyDiabetic macular edema apparently absentNo apparent retinal thickening or hard exudates in posterior poleDiabetic macular edema apparently presentSome apparent retinal thickening or hard exudates in posterior poleIf diabetic macular edema is present,it can be categorized as follows:Proposed disease severity levelFinding observable upon dilated ophthalmoscopyDiabetic macular edema presentMild diabetic macular edemaSome retinal thickening or hard exudates in posterior pole but distant from the center of the maculaModerate diabetic macular edemaRetinal thickening or hard exudates approaching the center of the macula but not involving the centerSevere diabetic macular edemaRetinal thickening or hard exudates involving the center of the macula

Glycemic controlThe relationship of glucose control and the chronic complications of diabetes has been extensively studied in observational studies.These studies all demonstrated that increased severity of diabetic retinopathy is associated with poorer glucose contral.

Randomized , controlled clinical trials of glycemic control were designed to address the causal role of glucose control in diabetic complications.ln the Diabetes Control and Complications Trial (DCCT),1441 patients with type 1 diabetes were randomly assigned to either conventional or intensive insulin treatment and followed for a period of 4 to 9 years.

Conventional treatment was characterized by one or two daily insulin injections, daily self-monitoring of urine or blood glucose, and diet and exercise education. Hemoglobin A1c (HbA1c) values were not used to guide treatment, unless an upper limit of 13% was exceeded.

Intensive treatment consisted of insulin administered three or more times daily by injection or an external pump, with dose adjusted according to self-monitoredblood glucose results performed at least four times per clay, as weIl as anticipated dietary intake and exercise, and with the goal of lowering HbA1c (measured monthly) to within the nondiabetic range (< 6.05%).

The DCCT demonstrated that intensive insulin treatment is associated with a decreased risk of either the development or progression of diabetic retinopathy in patients with type 1 diabetes.

The benefit of the strict control was also evident in patients with existing retinopathy (50% reduction in the rate of progressionof retinopathy compared with controls). At 6- and 12-month visits, a small adverse effect of intensive treatment on retinopathy progression was seen, similar to that described in other trials of glucose control.

However, in eyes with little or no retinopathy at the time of initiating intensive glucose control, this early worsening of retinopathy is unlikely to threaten vision. When the DCCT results were stratified by hemoglobin A1 C (HbA1 C) levels, there was a 35% to 40% reduction in the risk of retinopathy progression for every 10% decrease in HbA1C (e.g., from 8% to 7.2%).

With an additional 7 more years of foIlow-up when the HbA1Cs in both treatment groups were not statistically significant (8.1 % versus 8.2%, P = 0.09), the rate of progression of retinopathy remained statistically significantly less in those treated with the intensive therapy than in the conventional therapy.

The intensive glycemic control over a period of 6.5 years conferred benefits weIl beyond the period of treatment. These data have resulted in recommendations for achieving intense control with HbA1C level below 7% as soon as the diagnosis of diabetes is made.

The effect of glycemic control on the incidence and progression of diabetic retinopathy is similar in patients with type 2 diabetes, as assessed in observational studies and randomized studies conducted in Japan and the UK.

Findings in a study of Japanese patients with type 2 diabetes have shown that multiple insulin-injection treatment reduced the onset ofretinopathy from 32% to 8% and reduced a two-step progression retinopathy from 44% to 19%, compared with people receiving conventional insulin treatments over 6 years.

ln the UK Prospective Diabetes Study (UKPDS), the largest and longest study of patients with type 2 diabetes, there was a 25% reduction in the risk of the "any diabetes-related microvascular end point," including the need for retinal photocoagulation in the intensive treatment group compared to the conventional treatment group.

After 6 years of follow-up,a smaller proportion of patients in the intensive treatment group than in the conventional group had a two-step progression(worsening) in .diabetic retinopathy(P