Early Proliferative Diabetic Retinopathy Research Articles

Cataract surgery and diabetic retinopathy

Diabetes is a risk factor for the development of cataracts. Studies have shown an increased risk of ocular complications in diabetics after cataract surgery, but modern surgical techniques have minimized them, leading to an overall good visual outcome. Macular edema before surgery is the most common condition that limits post-operative visual recovery. Thus, pre-operative laser treatment is needed. Photocoagulation of preproliferative or early proliferative diabetic retinopathy is also advisable, due to the increased risk of iris neovascularization or retinopathy progression after surgery.

Efficacy of Octreotide in the Therapy of Severe Nonproliferative and Early Proliferative Diabetic Retinopathy: A Randomized Controlled Study

We appreciate both Dr. Gehrs' (1) careful examination of our study (2) on the efficacy of octreotide in the therapy of severe nonproliferative and early proliferative diabetic retinopathy and the opportunity to respond to her thoughtful comments. In response to her question concerning the baseline scores, the control group and octreotide-treated group baseline Early Treatment of Diabetic Retinopathy Study (ETDRS) scores were not different, with mean (± SD) values of 51.6 ± 4.0 for control and 51.6 ± 4.8 for treated groups. Although a reading center was not used in this pilot study, each retinal specialist used identical criteria for …

Results After Lens Extraction in Patients With Diabetic Retinopathy

To assess the visual results after surgical lens removal in patients with diabetic retinopathy. A multicenter randomized clinical trial designed to assess the effect of photocoagulation and aspirin in patients with mild to severe nonproliferative or early proliferative diabetic retinopathy and/or macular edema. Of the 3711 patients enrolled in the Early Treatment Diabetic Retinopathy Study, lens surgery was performed on 205 patients (270 eyes) during follow-up that ranged from 4 to 9 years. Visual acuity, macular edema status, and degree of diabetic retinopathy. In addition, risk factors associated with lens extraction and with poor postoperative visual acuity (worse than 20/100) were assessed. The risk of lens extraction increased with increasing age, female sex, and baseline proteinuria. Ocular variables associated with increased risk of lens surgery included poor baseline visual acuity and vitrectomy performed during the course of the study. At 1 year after lens surgery, visual acuity improvement of 2 or more lines from preoperative levels occurred in 64.3% of the operated-on eyes assigned to early photocoagulation and 59.3% of eyes assigned to deferral of photocoagulation. In eyes assigned to early photocoagulation, 46% of eyes achieved visual acuity better than 20/40; 73%, better than 20/100; and 8%, 5/200 or worse at 1 year after surgery. Visual acuity results for eyes assigned to deferral of laser photocoagulation at 1 year were not as favorable; 36% achieved visual acuity better than 20/40; 55%, better than 20/100; and 17%, 5/200 or worse at 1 year after surgery. Evaluation of 1-year postoperative visual acuities for all eyes with mild to moderate nonproliferative diabetic retinopathy at the annual visit before lens surgery showed that 53% were better than 20/40; 90%, better than 20/100; and 1%, 5/200 or worse. However, for eyes with severe nonproliferative or worse retinopathy at the annual visit before lens surgery, only 25% were better than 20/40; 42%, better than 20/100; and 22%, 5/200 or worse at 1 year after lens surgery. There was little change in visual acuity between 1 and 2 years postoperatively. Increased severity of retinopathy and poor visual acuity before surgery were associated with visual acuity of worse than 20/100 at 1 year after surgery. Lens surgery was associated with a borderline statistically significant increased risk of progression of diabetic retinopathy in the adjusted analyses (P = .03). No statistically significant long-term increased risk of macular edema was documented after lens surgery. Visual acuity results after lens surgery in patients in the Early Treatment Diabetic Retinopathy Study were better than published results for similar patients. This may be because of more intensive photocoagulation for lesions of diabetic retinopathy in the Early Treatment Diabetic Retinopathy Study than in previously reported studies. Although patients with severe nonproliferative retinopathy or worse before lens surgery had poorer visual results, visual improvement was seen in 55% of these patients at 1-year follow-up. The main causes of poor visual results in eyes after lens surgery were complications of proliferative retinopathy and/or macular edema.

Causes of severe visual loss in the early treatment diabetic retinopathy study: ETDRS report no. 24

PURPOSE: To describe the causes of and risk factors for persistent severe visual loss occurring in the Early Treatment Diabetic Retinopathy Study (ETDRS).METHODS: The ETDRS was a randomized clinical trial investigating photocoagulation and aspirin in 3,711 persons with mild to severe nonproliferative or early proliferative diabetic retinopathy. Severe visual loss, defined as best-corrected visual acuity of less than 5/200 on at least two consecutive 4-month follow-up visits, developed in 257 eyes (219 persons). Of these 257 eyes, 149 (127 persons) did not recover to 5/200 or better at any visit (persistent severe visual loss). Ocular characteristics of these eyes were compared with those of eyes with severe visual loss that improved to 5/200 or better at any subsequent visit. Characteristics of patients with severe visual loss that did and did not improve and those without severe visual loss were also compared.RESULTS: Severe visual loss that persisted developed in 149 eyes of 127 persons. In order of decreasing frequency, reasons recorded for persistent visual loss included vitreous or preretinal hemorrhage, macular edema or macular pigmentary changes related to macular edema, macular or retinal detachment, and neovascular glaucoma. Compared with all patients without persistent severe visual loss, patients with persistent severe visual loss had higher mean levels of hemoglobin A1c (10.4% vs 9.7%; P = .001) and higher levels of cholesterol (244.1 vs 228.5 mg/dl; P = .0081) at baseline. Otherwise, patients with persistent severe visual loss were similar to patients with severe visual loss that improved and to those without severe visual loss.CONCLUSIONS: Persistent severe visual loss was an infrequent occurrence in the ETDRS. Its leading cause was vitreous or preretinal hemorrhage, followed by macular edema or macular pigmentary changes related to macular edema and retinal detachment. The low frequency of persistent severe visual loss in the ETDRS is most likely related to the nearly universal intervention with scatter photocoagulation (either before or soon after high-risk proliferative diabetic retinopathy developed) and the intervention with vitreous surgery when clinically indicated.

Effects of Aspirin on Vitreous/Preretinal Hemorrhage in Patients With Diabetes Mellitus

To assess whether the use of aspirin exacerbates the severity or duration of vitreous/preretinal hemorrhages in patients with diabetic retinopathy. The Early Treatment Diabetic Retinopathy Study (ETDRS), a multicenter randomized clinical trial, was designed to assess the effect of photocoagulation and aspirin on 3711 patients with mild to severe nonproliferative or early proliferative diabetic retinopathy. Patients were randomly assigned to either an aspirin (650 mg/d) or a placebo group. One eye of each patient was randomly assigned to early photocoagulation and the other to deferral of photocoagulation. The severity and duration of the vitreous/preretinal hemorrhages were determined from gradings of the annual, seven standard stereoscopic field, fundus photographs. Clinical examinations scheduled every 4 months also provided information on the presence and duration of hemorrhages. Annual fundus photographs of eyes assigned to deferral of photocoagulation revealed vitreous/preretinal hemorrhages at some time during follow-up in 564 patients (30%) assigned to the placebo group and 585 patients (32%) assigned to the aspirin group (P = .48). Based on gradings of fundus photographs, there were no statistical differences in the severity of vitreous/preretinal hemorrhages (P = .11) or their rate of resolution (P = .86) between the groups. Clinical examination of eyes assigned to deferral of photocoagulation revealed 721 eyes (39%) assigned to the aspirin group and 689 (37%) assigned to the placebo group that had vitreous/preretinal hemorrhages during the course of the study (P = .30). Again, no statistically significant difference was found between the rates of resolution, as assessed clinically, between the two treatment groups (P = .43). As previously reported, the use of aspirin did not increase the occurrence of vitreous/preretinal hemorrhages in patients enrolled in the ETDRS. The data presented in this report demonstrate that the severity and duration of these hemorrhages were not significantly affected by the use of aspirin and that there were no ocular contraindications to its use (650 mg/d) in persons with diabetes who require it for treatment of cardiovascular disease or for other medical indications.

The effect of panretinal laser photocoagulation on visual acuity, visual fields and on subjective visual impairment in preproliferative and early proliferative diabetic retinopathy.

The effect of panretinal laser scatter treatment on visual fields, visual acuity and subjective complaints was assessed in 11 patients with severe nonproliferative or early proliferative diabetic retinopathy. Patients were prospectively examined before and after panretinal treatment using automated static threshold perimetry with program 30-2 on the Humphrey perimeter, and they were interviewed. Visual field sensitivity was often depressed even before treatment with mean MD -4.3 (-1, -11.6) dB, but was significantly lower (p < 0.01, ANOVA) 2 weeks after treatment with mean MD -8.6 dB. Visual fields remained stable 4 months later. Treatment increased the number of eyes with visual fields as defined by abnormal MD values at the p < 0.05 level from 8 to 16 among the 17 treated. In spite of considerable impairment of visual fields after treatment, subjective problems were small and the visual field impairment seemed to have little influence on everyday life.

Visual field loss with capillary non-perfusion in preproliferative and early proliferative diabetic retinopathy.

Thirty two eyes of 19 patients with capillary non-perfusion from preproliferative and early proliferative diabetic retinopathy underwent visual field testing on the 30-2 program of the Humphrey visual field analyser. The mean defect (MD) p value was < 5% in 30 (94%) eyes and the corrected pattern standard deviation (CPSD) was < 10% in 31 (97%) eyes. Areas of capillary non-perfusion demonstrated by fundal fluorescein angiography were closely associated with areas of reduced retinal sensitivity in these 31 eyes. More severe visual field defects were present in non-insulin dependent diabetics and in older patients. MD and CPSD p values of less than 0.5% and 1% respectively were found to be associated with non-insulin dependent diabetes (p < 0.05 and p < 0.01 respectively) and with the older age group (p < 0.05). There was no correlation between severity of field defects with hypertension and degree of retinopathy.

Pars Plana Vitrectomy in the Early Treatment Diabetic Retinopathy Study: ETDRS Report Number 17

The Early Treatment Diabetic Retinopathy Study (ETDRS) enrolled 3711 patients with mild-to-severe nonproliferative or early proliferative diabetic retinopathy in both eyes. Patients were randomly assigned to aspirin 650 mg/day or placebo. One eye of each patient was assigned randomly to early photocoagulation and the other to deferral of photocoagulation. Follow-up examinations were scheduled at least every 4 months, and photocoagulation was initiated in eyes assigned to deferral as soon as high-risk proliferative retinopathy was detected. Aspirin was not found to have an effect on retinopathy progression or rates of vitreous hemorrhage. The risk of a combined end point, severe visual loss or vitrectomy, was low in eyes assigned to deferral (6% at 5 years) and was reduced by early photocoagulation (4% at 5 years). Vitrectomy was carried out in 208 patients during the 9 years of the study. This report presents baseline and previtrectomy characteristics and visual outcome in these patients. Information collected at baseline and during follow-up as part of the ETDRS protocol was supplemented by review of clinic charts for visual acuity and ocular status immediately before vitrectomy. Vitrectomy was performed in 208 (5.6%) of the 3711 patients (243 eyes) enrolled in the ETDRS. The 5-year vitrectomy rates for eyes grouped by their initial photocoagulation assignment were as follows: 2.1% in the early full scatter photocoagulation group, 2.5% in the early mild scatter group, and 4.0% in the deferral group. The 5-year rates of vitrectomy (in one or both eyes) were 5.4% in patients assigned to aspirin and 5.2% in patients assigned to a placebo. The indications for vitrectomy were either vitreous hemorrhage (53.9%) or retinal detachment with or without vitreous hemorrhage (46.1%). Before vitrectomy, visual acuity was 5/200 or worse in 66.7% of eyes and better than 20/100 in 6.2%. One year after vitrectomy, the visual acuity was 20/100 or better in 47.6% of eyes, including 24.0% with visual acuity of 20/40 or better. With frequent follow-up examinations and timely scatter (panretinal) photocoagulation, the 5-year cumulative rate of pars plana vitrectomy in ETDRS patients was 5.3%. Aspirin use did not influence the rate of vitrectomy.

Effects of Aspirin Treatment on Diabetic Retionopathy: ETDRS Report Number 8

Aspirin treatment did not alter the course of diabetic retinopathy in patients enrolled in the Early Treatment Diabetic Retinopathy Study (ETDRS). In this randomized clinical trial supported by the National Eye Institute, 3711 patients with mild-to-severe nonproliferative or early proliferative diabetic retinopathy were assigned randomly to either aspirin (650 mg per day) or placebo. Aspirin did not prevent the development of high-risk proliferative retinopathy and did not reduce the risk of visual loss, nor did it increase the risk of vitreous hemorrhage. This was true both for eyes assigned randomly to deferral of photocoagulation and for eyes assigned randomly to early argon laser photocoagulation. The ETDRS results indicate that for patients with mild-to-severe nonproliferative or early proliferative diabetic retinopathy, it is likely that aspirin has no clinically important beneficial effects on the progression of retinopathy. The data also show that aspirin 650 mg per day had no clinically important harmful effects for diabetic patients with retinopathy. These findings suggest there are no ocular contraindications to aspirin when required for cardiovascular disease or other medical indications.

Early Photocoagulation for Diabetic Retinopathy: ETDRS Report Number 9

The Early Treatment Diabetic Retinopathy Study (ETDRS) enrolled 3711 patients with mild-to-severe nonproliferative or early proliferative diabetic retinopathy in both eyes. One eye of each patient was assigned randomly to early photocoagulation and the other to deferral of photocoagulation. Followup examinations were scheduled at least every 4 months and photocoagulation was initiated in eyes assigned to deferral as soon as high-risk proliferative retinopathy was detected. Eyes selected for early photocoagulation received one of four different combinations of scatter (panretinal) and focal treatment. This early treatment, compared with deferral of photocoagulation, was associated with a small reduction in the incidence of severe visual loss (visual acuity less than 5/200 at two consecutive visits), but 5-year rates were low in both the early treatment and deferral groups (2.6% and 3.7%, respectively). Adverse effects of scatter photocoagulation on visual acuity and visual field also were observed. These adverse effects were most evident in the months immediately following treatment and were less in eyes assigned to less extensive scatter photocoagulation. Provided careful follow-up can be maintained, scatter photocoagulation is not recommended for eyes with mild or moderate nonproliferative diabetic retinopathy. When retinopathy is more severe, scatter photocoagulation should be considered and usually should not be delayed if the eye has reached the high-risk proliferative stage. The ETDRS results demonstrate that, for eyes with macular edema, focal photocoagulation is effective in reducing the risk of moderate visual loss but that scatter photocoagulation is not. Focal treatment also increases the chance of visual improvement, decreases the frequency of persistent macular edema, and causes only minor visual field losses. Focal treatment should be considered for eyes with macular edema that involves or threatens the center of the macula.

Early Treatment Diabetic Retinopathy Study Design and Baseline Patient Characteristics: ETDRS Report Number 7

The Early Treatment Diabetic Retinopathy Study (ETDRS), a multicenter collaborative clinical trial supported by the National Eye Institute, was designed to assess whether argon laser photocoagulation or aspirin treatment can reduce the risk of visual loss or slow the progression of diabetic retinopathy in patients with mild-to-severe nonproliferative or early proliferative diabetic retinopathy. The 3711 patients enrolled in the ETDRS were assigned randomly to either aspirin (650 mg per day) or placebo. One eye of each patient was assigned randomly to early argon laser photocoagulation and the other to deferral of photocoagulation. Both eyes were to be examined at least every 4 months and photocoagulation was to be initiated in eyes assigned to deferral as soon as high-risk proliferative retinopathy was detected. Examination of a large number of baseline ocular and patient characteristics indicated that there were no important differences between randomized treatment groups at baseline.

Proliferative diabetic retinopathy

The pathogenesis of proliferative diabetic retinopathy is unknown. Although there are some established clinical and histological facts, the exact sequence of events is yet to be determined. Diabetic angiopathy is widespread in the body and appears to be a complication ofand related to the duration of the diabetic state. The essential difference between this and proliferative diabetic retinopathy is the absence of microaneurysm formation and neovascularization outside the eye. It thus seems that local ocular factors, either genetic, metabolic, or anatomical, modify the generalized response. The role of the last factor has not yet been investigated, so that it is not known whether the anatomical pattern of the retinal arteries and veins has any relationship to the sites and size of areas of neovascularization. It is the purpose of this paper to study the size and distribution of those areas in early proliferative diabetic retinopathy which are of sufficient size to be visible in fundus photographs and to subject them to statistical analysis to see if any definable pattern emerges.