Results after lens extraction in patients with diabetic retinopathy: early treatment diabetic retinopathy study report number 25.

OBJECTIVE: To assess the visual results after surgical lens removal in patients with diabetic retinopathy. DESIGN: 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. PARTICIPANTS: 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. OUTCOME MEASUREMENTS: 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. RESULTS: 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. CONCLUSIONS: 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.

Prevalence-value-accuracy plots: a new method for comparing diagnostic tests based on misclassification costs.

The clinical accuracy of diagnostic tests commonly is assessed by ROC analysis. ROC plots, however, do not directly incorporate the effect of prevalence or the value of the possible test outcomes on test performance, which are two important factors in the practical utility of a diagnostic test. We describe a new graphical method, referred to as a prevalence-value-accuracy (PVA) plot analysis, which includes, in addition to accuracy, the effect of prevalence and the cost of misclassifications (false positives and false negatives) in the comparison of diagnostic test performance. PVA plots are contour plots that display the minimum cost attributable to misclassifications (z-axis) at various optimum decision thresholds over a range of possible values for prevalence (x-axis) and the unit cost ratio (UCR; y-axis), which is an index of the cost of a false-positive vs a false-negative test result. Another index based on the cost of misclassifications can be derived from PVA plots for the quantitative comparison of test performance. Depending on the region of the PVA plot that is used to calculate the misclassification cost index, it can potentially lead to a different interpretation than the ROC area index on the relative value of different tests. A PVA-threshold plot, which is a variation of a PVA plot, is also described for readily identifying the optimum decision threshold at any given prevalence and UCR. In summary, the advantages of PVA plot analysis are the following: (a) it directly incorporates the effect of prevalence and misclassification costs in the analysis of test performance; (b) it yields a quantitative index based on the costs of misclassifications for comparing diagnostic tests; (c) it provides a way to restrict the comparison of diagnostic test performance to a clinically relevant range of prevalence and UCR; and (d) it can be used to directly identify an optimum decision threshold based on prevalence and misclassification costs.

Ganciclovir implant exchange. Timing, surgical procedure, and complications.

BACKGROUND: The ganciclovir implant is effective for the treatment of cytomegalovirus (CMV) retinitis. The device eventually runs out of drug, however, and must be replaced. We report our experience with exchanging ganciclovir implants during the course of a randomized clinical trial. METHODS: During our study, patients with newly diagnosed peripheral CMV retinitis were treated with a ganciclovir implant. The implant was scheduled for exchange at 32 weeks. It was exchanged earlier if progression of CMV retinitis occurred. Patient examinations and standard fundus photography were performed at 2-week intervals after the exchange procedure. RESULTS: Twenty-six exchange procedures were performed. Twenty-two eyes in 15 patients received a second implant and 4 eyes in 4 patients later received a third implant. Cytomegalovirus retinitis was rendered or maintained inactive in 22 of 23 cases with more than 1 month of follow-up after the second or third implants. Complications after the second implant procedure included transient vitreous hemorrhage in 5 eyes, postoperative inflammation in 1 eye, and retinal detachment in 1 eye. Median visual acuity returned to 20/25 by 28 days and to 20/20 by 42 days. Complications after the third implant procedure included dense vitreous hemorrhage in 3 of 4 eyes. Median survival time after a second implant procedure was 89 days. CONCLUSIONS: The initial ganciclovir implant exchange procedure is well tolerated with continued long-term control of CMV retinitis. Multiple reentries through the same wound may be associated with an increased risk for vitreous hemorrhage.

Association of visual field, cup-disc ratio, and magnetic resonance imaging of optic chiasm.

OBJECTIVE: To assess the association of visual field, vertical cup-disc (VC/D) ratio, and vertical height of optic chiasm. DESIGN: Case series. SETTING: Outpatient eye clinic. PATIENTS: Eighteen patients with low, normal, or elevated intraocular pressure, with or without visual field defects. INTERVENTION: Measurement of visual field, VC/D ratio, and vertical height of optic chiasm. MAIN OUTCOME MEASURES: Association between VC/D ratio and visual field defects compared with association between vertical height of optic chiasm and visual field defects. RESULTS: Visual field defects were graded as 0, 1 to 10, and 11 to 20 (from least to most severe). Group mean VC/D ratios were 0.47 (0), 0.55 (1-10), and 0.69 (11-20) for right eyes and 0.48 (0), 0.57 (1-10), and 0.75 (11-20) for left eyes. The significance level for trend was P = .02 for right eyes and P = .006 for left eyes. Group mean chiasm heights were 3.5 (0), 2.9 (1-10), and 2.2 (11-20) mm for right eyes and 3.5 (0), 2.8 (1-10), and 2.2 (11-20) mm for left eyes. The significance level for trend was P < .001 for right eyes and P = .002 for left eyes. To assess the simultaneous effects of VC/D ratio and chiasm height on the visual field defects groups, we used ordinal logistic regression models. Models with both variables implied that chiasm height was a stronger predictor of visual field defects group than VC/D ratio (for right eyes, P = .04 [VC/D ratio], P = .001 [chiasm height]; for left eyes, P = .11 [VC/D ratio], P = .005 [chiasm height]). CONCLUSIONS: When chiasm and VC/D ratio were analyzed in the same model, chiasm height was a stronger predictor of visual field defects. In advanced visual field defects, the optic chiasm is atrophic.

Association of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy. Early Treatment Diabetic Retinopathy Study (ETDRS) Report 22.

OBJECTIVE: To evaluate the relationship between serum lipid levels, retinal hard exudate, and visual acuity in patients with diabetic retinopathy. DESIGN: Observational data from the Early Treatment Diabetic Retinopathy Study. PARTICIPANTS: Of the 3711 patients enrolled in the Early Treatment Diabetic Retinopathy Study, the first 2709 enrolled had serum lipid levels measured. MAIN OUTCOME MEASURES: Baseline fasting serum lipid levels, best-corrected visual acuity, and assessment of retinal thickening and hard exudate from stereoscopic macular photographs. RESULTS: Patients with elevated total serum cholesterol levels or serum low-density lipoprotein cholesterol levels at baseline were twice as likely to have retinal hard exudates as patients with normal levels. These patients were also at higher risk of developing hard exudate during the course of the study. The risk of losing visual acuity was associated with the extent of hard exudate even after adjusting for the extent of macular edema. CONCLUSIONS: These data demonstrate that elevated serum lipid levels are associated with an increased risk of retinal hard exudate in persons with diabetic retinopathy. Although retinal hard exudate usually accompanies diabetic macular edema, increasing amounts of exudate appear to be independently associated with an increased risk of visual impairment. Lowering elevated serum lipid levels has been shown to decrease the risk of cardiovascular morbidity. The observational data from the Early Treatment Diabetic Retinopathy Study suggest that lipid lowering may also decrease the risk of hard exudate formation and associated vision loss in patients with diabetic retinopathy. Preservation of vision may be an additional motivating factor for lowering serum lipid levels in persons with diabetic retinopathy and elevated serum lipid levels.

Associations between siblings for esotropia and exotropia.

OBJECTIVE: To quantify familial aggregation of esotropia and exotropia in children examined in a large multicenter study. METHODS: Pregnant women and their children were examined in the Collaborative Perinatal Project of the National Institute of Neurological Disorders and Stroke, Bethesda, Md. Strabismus was evaluated in the children during follow-up examinations up to the age of 7 years. The second-order generalized estimating equations approach to logistic regression was used to estimate familial aggregation of esotropia and exotropia. RESULTS: For any pair of siblings, the odds for one sibling having esotropia more than doubled when the other sibling had esotropia. For exotropia, there were differences in sibling associations based on birth relationships. In particular, there was no statistically significant association between siblings from separate single births. On the other hand, for the pairs of siblings from multiple births (ie, twins, triplets, and quadruplets), the odds for exotropia in one sibling were increased by at least a factor of 17 when the other sibling from that birth also had exotropia. For both esotropia and exotropia, adjustment for previously identified risk factors only somewhat reduced the magnitudes of the observed associations. Limited data on zygosity showed a stronger association between monozygotic twins than between dizygotic twins. CONCLUSIONS: There is a significant familial component in the cause of strabismus. Furthermore, there are important contributions to this familial aggregation beyond those associated with known risk factors for strabismus.

Metabolic control and progression of retinopathy. The Diabetes in Early Pregnancy Study. National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study.

OBJECTIVE: To evaluate the role of metabolic control in the progression of diabetic retinopathy during pregnancy. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study of 155 diabetic women in the Diabetes in Early Pregnancy Study followed from the periconceptional period to 1 month postpartum. Fundus photographs were obtained shortly after conception (95% within 5 weeks of conception) and within 1 month postpartum. Glycosylated hemoglobin was measured weekly during the 1st trimester and monthly thereafter. RESULTS: In the 140 patients who did not have proliferative retinopathy at baseline, progression of retinopathy was seen in 10.3, 21.1, 18.8, and 54.8% of patients with no retinopathy, microaneurysms only, mild nonproliferative retinopathy, and moderate-to-severe nonproliferative retinopathy at baseline, respectively. Proliferative retinopathy developed in 6.3% with mild and 29% with moderate-to-severe baseline retinopathy. Elevated glycosylated hemoglobin at baseline and the magnitude of improvement of glucose control through week 14 were associated with a higher risk of progression of retinopathy (adjusted odds ratio for progression in those with glycohemoglobin > or = 6 SD above the control mean versus those within 2 SD was 2.7; 95% confidence interval was 1.1-7.2; P = 0.039). CONCLUSIONS: The risk for progression of diabetic retinopathy was increased by initial glycosylated hemoglobin elevations as low as 6 SD above the control mean. This increased risk may be due to suboptimal control itself or to the rapid improvement in metabolic control that occurred in early pregnancy. Excellent metabolic control before conception may be required to avoid this increase in risk. Those with moderate-to-severe retinopathy at conception need more careful ophthalmic monitoring, particularly if their diabetes was suboptimally controlled at conception.

Digoxin does not accelerate progression of diabetic retinopathy.

OBJECTIVE: To test the hypothesis that digoxin, an inhibitor of Na(+)-K(+)-ATPase activity, accelerates the progression of diabetic retinopathy. RESEARCH DESIGN AND METHODS: We compared the incidence and risk of retinopathy in 120 digoxin-taking vs. 867 non-digoxin-taking diabetic participants in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) and in 117 digoxin-taking vs. 1,883 non-digoxin-taking diabetic subjects in the Early Treatment Diabetic Retinopathy Study (ETDRS). In both studies, retinopathy was detected by grading stereoscopic color photographs using the modified Airlie House classification scheme, and a two-step difference in baseline retinopathy grade was considered significant. RESULTS: After controlling for other risk factors, we found no statistically significant association with either 4-year incidence of retinopathy (WESDR) or progression of retinopathy (WESDR and ETDRS) in patients taking digoxin at baseline compared with those not taking digoxin. CONCLUSIONS: These data suggest that digoxin therapy does not adversely affect the course of diabetic retinopathy.

Effects of aspirin on vitreous/preretinal hemorrhage in patients with diabetes mellitus. Early Treatment Diabetic Retinopathy Study report no. 20.

OBJECTIVE: To assess whether the use of aspirin exacerbates the severity or duration of vitreous/preretinal hemorrhages in patients with diabetic retinopathy. DESIGN: 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. INTERVENTION: 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. MAIN OUTCOME MEASURES: 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. RESULTS: 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). CONCLUSIONS: 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.

Accommodative amplitudes in the Early Treatment Diabetic Retinopathy Study.

PURPOSE: Accommodative amplitude in persons with diabetes was investigated using data collected as part of the Early Treatment Diabetic Retinopathy Study. METHODS: Accommodative amplitude was measured at the baseline visit in 1,058 patients who had good visual acuity and who were less than 46 years old. Risk factors for low accommodative amplitude at baseline were evaluated using multivariable linear regression. Change in accommodative amplitude after photocoagulation was evaluated using paired t tests and repeated measures analysis of variance for the 578 patients who underwent follow-up measurements at the 4-month visit. RESULTS: Accommodative amplitudes in Early Treatment Diabetic Retinopathy Study patients were lower than normal accommodative amplitudes. Older age (P < 0.001) and increased duration of diabetes (P < 0.01) were risk factors associated with low amplitudes of accommodation in the Early Treatment Diabetic Retinopathy Study. Full scatter photocoagulation was associated with an apparently transient additional reduction in accommodative amplitude; a one third diopter loss in accommodative amplitude was demonstrated only at the 4-month visit (P < 0.001). CONCLUSION: This study demonstrates that diabetes and duration of diabetes, along with age, are important risk factors for reduced accommodative amplitude. These factors along with an apparently transient decrease in accommodative amplitude following scatter photocoagulation should be considered when assessing the accommodative needs of patients with diabetes and when discussing side effects of full scatter photocoagulation.

Treatment of cytomegalovirus retinitis with an intraocular sustained-release ganciclovir implant. A randomized controlled clinical trial.

BACKGROUND AND METHODS: We performed a randomized controlled clinical trial to assess the safety and efficacy of a 1 microgram/h ganciclovir implant for the treatment of newly diagnosed cytomegalovirus (CMV) retinitis in patients with the acquired immunodeficiency syndrome (AIDS). Patients with previously untreated peripheral CMV retinitis were randomly assigned either to immediate treatment with the ganciclovir implant or to deferred treatment. Standardized fundus photographs were taken at 2-week intervals and analyzed in a masked fashion. The study end point was progression of retinitis based on the photographic assessment. RESULTS: Twenty-six patients (30 eyes) were enrolled. The median time to progression of retinitis was 15 days in the deferred treatment group (n = 16) vs 226 days in the immediate treatment group (n = 14) (P < .00001, log-rank test). During the study, 39 primary implants and 12 exchange implants were placed in immediate-treatment eyes, deferred-treatment eyes that progressed, or contralateral eyes that developed CMV retinitis. Postoperative complications in the total series included seven late retinal detachments and one retinal tear without detachment. Final visual acuity was 20/25 or better in 34 of 39 eyes. The estimated risk of developing CMV retinitis in the fellow eye was 50% at 6 months. Biopsy-proven visceral CMV disease developed in eight (31%) of 26 patients. The median survival was 295 days. CONCLUSION: The ganciclovir implant is effective for the treatment of CMV retinitis. Patients with unilateral CMV retinitis treated with the implant are likely to develop CMV retinitis in the fellow eye, and some patients will develop visceral CMV disease.

Risk factors for esotropia and exotropia.

OBJECTIVE: To identify risk factors associated with the two major types of strabismus--esotropia and exotropia--in a cohort of children followed up from gestation to age 7 years. DESIGN: Pregnant women were enrolled in the Collaborative Project of the National Institute of Neurological Disorders and Stroke, Bethesda, Md, from 1959 to 1965 at 12 university centers. This large multidisciplinary study was designed to evaluate the developmental consequences of complications during pregnancy and the perinatal period. Data on maternal, socioeconomic, perinatal, and neonatal characteristics were collected from 39,227 children and their mothers by medical examination and interview. Examinations of the children were performed at birth, 4 months, 8 months, 1 year, and 7 years. OUTCOME MEASURES: The evaluation of the presence of strabismus was performed during follow-up examinations and confirmed at the 7-year follow-up visit. Potential risk factors for strabismus were evaluated from the maternal, socioeconomic, perinatal, and neonatal characteristics. RESULTS: Esotropia developed in 1187 children (3.0%), and exotropia developed in 490 children (1.2%). Esotropia was more common in whites (3.9% in whites vs 2.2% in blacks, P < .0001). The occurrence of exotropia was similar in the two races (1.2% in whites and 1.3% in blacks). Results of multivariable logistic regression models showed that the risk of strabismus increased with low birth weight (P < .0001). For infants weighing 1500 g at birth compared with those weighing 4000 g at birth, the odd ratios were 3.26 (95% confidence interval, 2.50 to 4.25) for esotropia and 4.01 (95% confidence interval, 2.77 to 5.80) for exotropia. Maternal cigarette smoking during pregnancy also increased the risk of each type of strabismus (P < .0001). For offspring of mothers who smoked more than two packs of cigarettes per day compared with those whose mothers did not smoke, the odds ratios were 1.83 (95% confidence interval, 1.51 to 2.22) for esotropia and 2.32 (95% confidence interval, 1.72 to 3.13) for exotropia. Maternal age was also a significant risk factor for esotropia (P = .0005). The risk of esotropia increased with increasing age until age 34 years. In particular, the odds ratio for mothers aged 30 to 34 years relative to that for mothers aged 20 to 24 years was 1.43 (95% confidence interval, 1.19 to 1.70). CONCLUSIONS: Esotropia was more common in whites than in blacks. The occurrence of exotropia was similar in the two races. Maternal cigarette smoking during pregnancy and low birth weight were independent and important risk factors for both esotropia and exotropia. There was an increased risk of esotropia with increasing maternal age.

Radial keratotomy does not affect intraocular pressure.

BACKGROUND: Recent reports have suggested that a secondary effect of radial keratotomy may be a reduction in intraocular pressure (IOP) levels. METHODS: In an effort to study the relationship of radial keratotomy to IOP, we compared the mean IOP from the baseline and follow-up visits during 1 year after surgery of operated versus nonoperated eyes of patients enrolled in the Prospective Evaluation of Radial Keratotomy (PERK) study. To investigate if radial keratotomy had more of an effect on eyes with higher baseline IOPs, the same analysis was performed on a subset (134 patients) who had a baseline IOP of 15 mm Hg or greater. RESULTS: The average baseline IOP for both operated eyes and nonoperated eyes was 14.6 mm Hg. There was no significant difference in mean IOP between operated and nonoperated eyes across all time points (p = .18). Although mean IOP changed over time, it did not clinically differ in operated versus nonoperated eyes at any time point. These findings were similar in the analysis of eyes with higher baseline IOP (15 mm Hg or greater). CONCLUSION: We conclude that the radial keratotomy performed in the PERK study had no effect on IOP within 1 year after surgery.

Arteriovenous crossing patterns in branch retinal vein occlusion. The Eye Disease Case-Control Study Group.

PURPOSE: The study was designed to evaluate the relative anatomic position of the crossing vessels at the site of occlusion in eyes with branch retinal vein occlusion (BRVO). METHODS: Fundus photographs of 106 eyes (104 patients) with recent BRVO from the Eye Disease Case-Control Study were used to examine the relative position of artery and vein at occluded crossings. Three separate comparison groups were formed by identifying corresponding arteriovenous crossings for each occluded crossing in: (1) the ipsilateral but opposite vessel arcade within eyes affected by BRVO; (2) the same quadrant in unaffected eyes of BRVO patients; and (3) the same quadrant in eyes of patients without BRVO, matched by age, sex, and race with the BRVO patients. RESULTS: The site of obstruction of the branch vein was an arteriovenous crossing in all affected eyes. In 99% of eyes with BRVO, the artery was located anterior to the vein at the obstructed site. In the three comparison groups, the artery was anterior to the vein in 62%, 61%, and 54% of the crossings, respectively, yielding statistically significant differences for each group of control crossings compared with BRVO crossings (P < 0.001). CONCLUSION: Finding the vein to be consistently between the more rigid artery and the retina at almost all arteriovenous crossings affected by BRVO suggests a possible role for mechanical obstruction in the pathogenesis of BRVO.

Pars plana vitrectomy in the Early Treatment Diabetic Retinopathy Study. ETDRS report number 17. The Early Treatment Diabetic Retinopathy Study Research Group.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Aspirin effects on the development of cataracts in patients with diabetes mellitus. Early treatment diabetic retinopathy study report 16.

The Early Treatment Diabetic Retinopathy Study, a randomized clinical trial supported by the National Eye Institute, was designed to assess the effect of photocoagulation and aspirin in 3711 patients with mild to severe nonproliferative or early proliferative diabetic retinopathy. Although the primary goal of the study was to evaluate the effect of photocoagulation and aspirin on diabetic retinopathy, the study also provided an opportunity to evaluate the effects of aspirin on the development of cataract. No evidence showed that aspirin use reduced the risk of development of cataract requiring extraction (4.1% vs 4.3% in patients assigned to aspirin or placebo treatment, respectively; Mantel-Cox P = .77; relative risk, 1.05; 99% confidence interval, 0.73 to 1.51). Aspirin use also did not reduce the risk of less extensive but visually significant lens opacities developing (29.6% vs 28.3%; Mantel-Cox P = .76; relative risk, 0.99; 99% confidence interval, 0.85 to 1.15). Early Treatment Diabetic Retinopathy Study results do not support the hypothesis that aspirin (at a dose of 650 mg/d) reduces the risk of cataract development in this diabetic population.

Acceptable values of kappa for comparison of two groups.

A model was developed for a simple clinical trial in which graders had defined probabilities of misclassifying pathologic material to disease present or absent. The authors compared Kappa between graders, and efficiency and bias in the clinical trial in the presence of misclassification. Though related to bias and efficiency, Kappa did not predict these two statistics well. These results pertain generally to evaluation of systems for encoding medical information, and the relevance of Kappa in determining whether such systems are ready for use in comparative studies. The authors conclude that, by itself, Kappa is not informative enough to evaluate the appropriateness of a grading scheme for comparative studies. Additional, and perhaps difficult, questions must be addressed for such evaluation.