Craig M. Greven

Effects of medical therapies on retinopathy progression in type 2 diabetes.

BACKGROUND We investigated whether intensive glycemic control, combination therapy for dyslipidemia, and intensive blood-pressure control would limit the progression of diabetic retinopathy in persons with type 2 diabetes. Previous data suggest that these systemic factors may be important in the development and progression of diabetic retinopathy. METHODS In a randomized trial, we enrolled 10,251 participants with type 2 diabetes who were at high risk for cardiovascular disease to receive either intensive or standard treatment for glycemia (target glycated hemoglobin level, <6.0% or 7.0 to 7.9%, respectively) and also for dyslipidemia (160 mg daily of fenofibrate plus simvastatin or placebo plus simvastatin) or for systolic blood-pressure control (target, <120 or <140 mm Hg). A subgroup of 2856 participants was evaluated for the effects of these interventions at 4 years on the progression of diabetic retinopathy by 3 or more steps on the Early Treatment Diabetic Retinopathy Study Severity Scale (as assessed from seven-field stereoscopic fundus photographs, with 17 possible steps and a higher number of steps indicating greater severity) or the development of diabetic retinopathy necessitating laser photocoagulation or vitrectomy. RESULTS At 4 years, the rates of progression of diabetic retinopathy were 7.3% with intensive glycemia treatment, versus 10.4% with standard therapy (adjusted odds ratio, 0.67; 95% confidence interval [CI], 0.51 to 0.87; P=0.003); 6.5% with fenofibrate for intensive dyslipidemia therapy, versus 10.2% with placebo (adjusted odds ratio, 0.60; 95% CI, 0.42 to 0.87; P=0.006); and 10.4% with intensive blood-pressure therapy, versus 8.8% with standard therapy (adjusted odds ratio, 1.23; 95% CI, 0.84 to 1.79; P=0.29). CONCLUSIONS Intensive glycemic control and intensive combination treatment of dyslipidemia, but not intensive blood-pressure control, reduced the rate of progression of diabetic retinopathy. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov numbers, NCT00000620 for the ACCORD study and NCT00542178 for the ACCORD Eye study.)

Intraocular foreign bodies: management, prognostic factors, and visual outcomes.

OBJECTIVE To determine prognostic factors and visual outcomes in patients with intraocular foreign bodies (IOFBs). DESIGN Retrospective, noncomparative, interventional case series. PARTICIPANTS Fifty-nine consecutive patients undergoing removal of an IOFB with a minimum of 6 months of follow-up. INTERVENTION Surgical removal of the IOFB and repair of associated ocular trauma. MAIN OUTCOME MEASURES Final best corrected visual acuity was the main outcome measured. Ocular findings at presentation were compared with final visual acuity to determine prognostic factors for visual outcome. RESULTS Final best corrected visual acuity of 20/40 or more was obtained in 42 patients (71%) and ambulatory vision (>5/200) was achieved in 50 patients (85%). Presenting visual acuity was predictive of final visual outcome (P < 0.01). Prognostic factors for a better visual outcome (P < 0.05) included better presenting visual acuity and hammering metal on metal as the mechanism of injury. Prognostic factors for a poor outcome (P < 0.05) included poor presenting visual acuity, the presence of an afferent pupillary defect, and vitreous hemorrhage. CONCLUSIONS Final visual outcomes were excellent in 71% of patients. Presenting visual acuity was the strongest predictor of final visual outcome in this series. Additional predictive factors included the mechanism of injury, the presence of an afferent pupillary defect, and vitreous hemorrhage.

Retinal Arterial Occlusions in Young Adults

PURPOSE To determine the cause, associated factors, visual results, and systemic morbidity in patients less than 40 years old with retinal arterial occlusions. METHODS We studied 27 eyes with nontraumatic retinal arterial occlusions in 21 patients less than 40 years old (range, 22 to 38 years; mean, 28 years). RESULTS Of the 21 patients, branch retinal artery (arteriolar) occlusion occurred in 15 (71%), central retinal artery occlusion occurred in five (24%), and cilioretinal artery occlusion occurred in one (5%). Retinal artery occlusions were bilateral in six patients (29%) and occurred in 14 women (67%). Emboli were identifiable in seven patients (33%). Cardiac valvular disease was the most commonly recognized etiologic agent and was present in four patients (19%). Various associated factors leading to a hypercoagulable state or embolic condition were identified in 19 patients (91%). CONCLUSION Retinal arterial occlusions in young adults occur via multiple mechanisms. Systemic evaluation allows detection of a risk factor for retinal arterial occlusive disease in most patients.

Surgical Removal of Massive Subretinal Hemorrhage Associated with age-related Macular Degeneration

The authors report on 11 patients with age-related macular degeneration associated with massive subretinal hemorrhage, who were treated with surgical removal of the hemorrhage and associated fibrosis. Preoperative visual acuity ranged from 20/400 to hand motions. Postoperative visual acuity ranged from 20/200 to light perception with a minimum of 3 months of follow-up. Complications included partial or total retinal detachment in four patients (36%) and cataract in four patients (36%). Four of 11 patients showed some improvement in vision (36%). All four of these patients had surgery within 1 week of the onset of severe visual loss. Although surgical removal of large subretinal hemorrhages is technically feasible, visual recovery is limited, even in uncomplicated cases, by macular degenerative changes.

Atypical, Severe Toxoplasmic Retinochoroiditis in Elderly Patients

BACKGROUND The diagnosis of toxoplasmic retinochoroiditis is based primarily on characteristic ocular findings, with supportive serologic evidence. Clinical recognition of atypical presentations is critical for timely antiparasitic drug therapy. METHODS Case histories were reviewed for seven presumed immunocompetent elderly patients with atypically severe (multifocal or diffuse or both) toxoplasmic retinochoroiditis. Three cases initially were misdiagnosed as acute retinal necrosis syndrome. The correct diagnosis was confirmed in each case by response to antiparasitic drug therapy, polymerase chain reaction studies of intraocular specimens, or histopathologic analysis. RESULTS The patients ranged in age from 69 to 82 years (median, 74 years). Only three patients had intercurrent medical conditions that may be associated with subtle immune dysfunction (diabetes mellitus and hepatitis C). The extensive necrotizing retinochoroiditis in each patient was nonhemorrhagic and not associated with occlusive retinal arteritis. Despite prompt response to antiparasitic drug therapy, prolonged treatment usually was required, and four patients had retinitis reactivation after discontinuing treatment. Significant visual loss accompanied the infection in most eyes. CONCLUSION Toxoplasmosis should be considered as a cause of multifocal or diffuse necrotizing retinitis or both in elderly patients. Older patients may be more susceptible to severe ocular Toxoplasma infections because of age-related decline in cell-mediated immunity and chronic underlying diseases.

Scleral Buckling in Stages 4B and 5 Retinopathy of Prematurity

Twenty-two eyes with traction retinal detachment (RD) secondary to retinopathy of prematurity (ROP) in 21 infants were treated by scleral buckling in combination with external cryotherapy and drainage of subretinal fluid. Anatomic reattachment of the retina was achieved in 13 (59%) of 22 eyes. Of those patients achieving anatomic reattachment with follow-up of 18 months or more, four (40%) of ten had 20/400 or better visual acuity.

The Effects of Medical Management on the Progression of Diabetic Retinopathy in Persons with Type 2 Diabetes: The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study

PURPOSE To report additional ocular outcomes of intensive treatment of hyperglycemia, blood pressure, and dyslipidemia in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. DESIGN Double 2×2 factorial, multicenter, randomized clinical trials in people with type 2 diabetes who had cardiovascular disease or cardiovascular risk factors. In the glycemia trial, targets of intensive and standard treatment were: hemoglobin A1c <6.0% and 7.0% to 7.9%, respectively, and in the blood pressure trial: systolic blood pressures of <120 and <140 mmHg, respectively. The dyslipidemia trial compared fenofibrate plus simvastatin with placebo plus simvastatin. PARTICIPANTS Of the 3472 ACCORD Eye Study participants enrolled, 2856 had 4-year data (85% of survivors). METHODS Eye examinations and fundus photographs were taken at baseline and year 4. Photographs were graded centrally for retinopathy severity and macular edema using the Early Treatment Diabetic Retinopathy Study (ETDRS) methods. MAIN OUTCOME MEASURES Three or more steps of progression on the ETDRS person scale or treatment of retinopathy with photocoagulation or vitrectomy. RESULTS As previously reported, there were significant reductions in the primary outcome in the glycemia and dyslipidemia trials, but no significant effect in the blood pressure trial. Results were similar for retinopathy progression by 1, 2, and 4 or more steps on the person scale and for ≥ 2 steps on the eye scale. In the subgroup of patients with mild retinopathy at baseline, effect estimates were large (odds ratios, ∼0.30; P < 0.001), but did not reach nominal significance for participants with no retinopathy or for those with moderate to severe retinopathy at baseline. CONCLUSIONS Slowing of progression of retinopathy by intensive treatment of glycemia was observed in ACCORD participants, whose average age and diabetes duration were 62 and 10 years, respectively, and who had cardiovascular disease or cardiovascular risk factors. The effect seemed stronger in patients with mild retinopathy. Similar slowing of progression was observed in patients treated with fenofibrate, with no effect observed with intensive blood pressure treatment. This is the second study to confirm the benefits of fenofibrate in reducing diabetic retinopathy progression, and fenofibrate should be considered for treatment of diabetic retinopathy.

Epiretinal Membrane Release and Posterior Vitreous Detachment

The spontaneous release of epiretinal membranes is a rare clinical phenomenon, the mechanism of which is poorly understood. The authors present three patients with epiretinal macular membranes associated with peripheral retinal lesions, in whom spontaneous release of the membrane occurred in conjunction with detachment of the posterior vitreous. In each patient, the membrane remained attached to the posterior vitreous face, and in each eye there was a decrease in retinal striae and an improvement in vision. The authors postulate that posterior vitreous separation was the mechanism by which these membranes detached from the macula.

Protein S deficiency and bilateral branch retinal artery occlusion

A macular branch retinal artery occlusion developed in the right eye of a 25-year-old woman when she was 38 weeks pregnant. She subsequently presented 5 days postpartum with a branch retinal artery occlusion in her left eye. Although her initial work-up did not reveal a source for her occlusions, subsequent studies have documented a deficiency of protein S.

The spectrum of cavitary optic disc anomalies in a family.

The current classification of cavitary optic disc anomalies including the morphologically related entities--optic nerve pit, morning glory disc anomaly, coloboma of the optic nerve, and retinochoroidal coloboma involving the optic nerve--is inexact and confusing. Traditionally, these disc abnormalities have been regarded as distinct morphologic anomalies. Thirty-five members of a five-generation kindred with autosomal dominantly inherited optic disc anomalies were examined. Observed abnormalities in this pedigree comprised a spectrum of morphologic variants ranging from large anomalous discs to typical pits and colobomas. The findings in this family suggest a variable expression of a single autosomal dominant defect rather than the chance occurrence of three separate, distinct, but morphologically similar entities occurring in a single pedigree.