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Background: The coexistence of fundus torpedoes and Gardner syndrome was initially reported in 1989 and 1992 by Gass and Roseman. Gardner syndrome is a dominantly inherited disease characterized by a multitude of potentially lethal gastrointestinal polyps. Over the ensuing quarter century, several publications demonstrated uncommon, but easily recognized, fundus lesions called Torpedo Maculopathy in apparently normal individuals. These fundus abnormalities were thought to be single and isolated without systemic associations. During the same period of time, a variety of nonspecific fundus abnormalities were described in Gardner syndrome, which, in retrospect, included highly specific lesions that closely resembled macular torpedoes and sometimes were indistinguishable from them.Patient and methods: We now report a confirmed case of Gardner syndrome with numerous fundus torpedoes, and carefully analyze the voluminous literature of both Gardner syndrome and Torpedo Maculopathy.Results: We demonstrate shared features of the fundus lesions in both diseases, and hypothesize that they may have genetic as well as ophthalmoscopic similarities in common.Conclusions: We therefore recommend that individuals with classic isolated torpedoes undergo evaluations for mutations in the Gardner gene (Adenomatous polyposis coli) and for the presence of gastrointestinal polyps and other systemic features of Gardner syndrome. We also suggest that apparently normal individuals, who are genetically related to patients with known classic torpedoes, undergo inspection of their fundi for the possible presence of characteristic lesions.

Purpose: This work analyzes data from a series of surveys developed by the American Society of Retina Specialists (ASRS) that assesses the impact of COVID-19 on physicians, their practices, and their patients. Methods: Five surveys were sent by the ASRS between March and July 2020 to more than 2600 US and international retina specialists. Data and trends from these surveys were analyzed. Results: Most responding retina specialists (87%-95% in the United States and internationally) reported having no known COVID-related symptoms despite reported limitations in personal protective equipment. Clinic volumes globally were drastically reduced in March 2020 with only partial recovery through July 2020, which was slower internationally than in the United States. Practices were compelled to reduce staff and physician employment levels. Most respondents estimated some degree of delay in patient treatment with corresponding declines in vision and/or anatomy that were attributed most frequently to patients’ fears of the pandemic and least frequently to office unavailability. Conclusions: The reported impact of COVID-19 on retina specialists, their practices, and their patients has been substantial. Although retina specialists were quickly resilient in optimizing delivery of patient care in a manner safe for patients and providers, the reduction in clinic volume has been devastating in the United States and internationally, with negative impacts on patient outcomes, reductions in practices’ volume and employment, and risk to practices’ financial health. Future studies will be required to quantify losses associated with these unprecedented and ongoing circumstances caused by the pandemic.

Purpose To assess the immunohistochemical and histopathologic changes in a subject with autosomal dominant vitreoretinochoroidopathy (ADVIRC). Design Research manuscript. Participant A 92-year-old white man with ADVIRC. Methods The subject was documented clinically for 54 years. The retina/choroid complex of the right eye was evaluated with cryosections stained with hematoxylin–eosin or periodic acid–Schiff (PAS) reagent. Cryosections also were evaluated with immunofluorescence or alkaline phosphatase (APase) immunohistochemistry (IHC) using primary antibodies against bestrophin 1 (BEST1), glial fibrillary acidic protein (GFAP), pigment epithelium–derived factor (PEDF), RPE65, transforming growth factor (TGF)-β, vascular endothelial growth factor (VEGF), and vimentin. The left retina and choroid were evaluated as flatmounts using immunofluorescence. Ulex europaeus agglutinin (UEA) lectin was used to stain viable vasculature. Main Outcome Measures The immunohistochemical and histopathologic changes in retina and choroid from a subject with ADVIRC. Results The subject had a heterozygous c.248G>A variant in exon 4 of the BEST1 gene. There was widespread chorioretinal degeneration and atrophy except for an island of spared retinal pigment epithelium (RPE) monolayer in the perimacula/macula in both eyes. In this region, some photoreceptors were present, choriocapillaris (CC) was spared, and RPE cells were in their normal disposition. There was a Muller cell periretinal membrane throughout much of the fundus. Bestrophin-1 was not detected or only minimally present by IHC in the ADVIRC RPE, even in the spared RPE area. Beyond the island of retained RPE monolayer on Bruch's membrane (BrMb), there was migration of RPE into the neuroretina, often ensheathing blood vessels and producing excessive matrix within their perivascular aggregations. Conclusions The primary defect in ADVIRC is in the RPE, the only cells in the eye that express the BEST1 gene. The dysfunctional RPE cells may go through epithelial/mesenchymal transition as they migrate from BrMb to form papillary aggregations in the neuroretina, often ensheathing blood vessels. This may be the reason for retinal blood vessel nonperfusion. Migration of RPE from BrMb also was associated with attenuation of the CC.

Mutations in BEST1 account for autosomal dominant vitreoretinochoroidopathy (ADVIRC), a rare inherited retinal dystrophy with presenile cataracts and incomplete anterior segment development. The long-term clinical findings and visual prognosis of these patients continues to evolve over time.The retina was assessed by fundus photography, fluorescein angiography, and spectral domain optical coherence tomography. Sanger dideoxy chain-termination sequencing identified mutations in BEST1. Bioinformatic tools were used to predict changes in splicing. An in vitro splicing assay was applied to evaluate for altered pre-mRNA splicing.Long-term follow up of the first ever reported ADVIRC proband revealed progressive foveal atrophy in both eyes 3 decades after his initial presentation. Progressive retinal ischemia, bilateral iris atrophy, and pseudophakodnesis were observed on follow up. The patient was heterozygous for a c.248G A missense mutation in exon 4 of BEST1, affecting a highly conserved transmembrane domain. Although computational prediction models suggest a change in the binding probability of splicing-associated SR proteins, in vitro splicing assays failed to demonstrate an effect of the c.248G A mutation on splicing of BEST1 exon 3 or exon 4.Progressive posterior chorioretinal changes occurred over time in the initial ADVIRC proband, leading to visual loss. The causative mutation in this patient falls in the transmembrane domain of the BEST1 protein, with unclear functional consequences. Although previous studies showed alteration in pre-mRNA splicing, in vitro splicing assays failed to demonstrate this in our patient.

Purpose To describe a new classification of stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR). Design Retrospective case series and literature review. Participants A total of 17 patients from 5 institutions. Methods Detailed case history, multimodal imaging, and genetic testing were reviewed for patients with macular schisis without a known predisposing condition. Patients with a stellate appearance centered on the fovea with correlating confirmed expansion of the outer plexiform layer (OPL) by optical coherence tomography (OCT) were included. Exclusion criteria included a family history of macular retinoschisis, a known genetic abnormality associated with retinoschisis, myopic traction maculopathy, epiretinal membrane, vitreoretinal traction, optic or scleral pit, or advanced glaucomatous optic nerve changes. Main Outcome Measures Clinical features, anatomic characteristics, and visual acuity. Results A total of 22 eyes from 16 female patients and 1 male patient with foveomacular schisis were reviewed from 5 institutions. Initial visual acuity was ≥20/50 in all eyes (mean, 20/27), but visual acuity in a single eye decreased from 20/20 to 20/200 after the development of subfoveal fluid. The refractive status was myopic in 16 eyes, plano in 3 eyes, and hyperopic in 2 eyes. Three eyes had a preexisting vitreous separation, and 19 eyes had an attached posterior hyaloid. Follow-up ranged from 6 months to >5 years. Conclusions In this largest known series of patients with SNIFR, all patients demonstrated splitting of the OPL in the macula with relatively preserved visual acuity (≥20/40) except in a single patient in whom subretinal fluid developed under the fovea.

Purpose The purpose of this was to describe the clinical improvement of chronic central serous chorioretinopathy in a patient treated with rifampin for tuberculosis. Methods A 54-year-old Hispanic man with a distant history of pulmonary tuberculosis presented with reduced vision in the right greater than left eye for over 1 year. He had diffuse chorioretinopathy in both eyes and a serous retinal detachment in his right eye. The findings were most consistent with chronic central serous chorioretinopathy, although tuberculosis -related choroiditis could not be excluded. Treatment with multidrug antituberculosis medications, including rifampin, resulted in the reduction in leakage and resolution of subretinal fluid. Fluid recurred on cessation of all medications and resolved again with retreatment. Monotherapy with rifampin maintained the absence of fluid. Discussion This case represents the first report of chronic central serous chorioretinopathy responding to systemic therapy with rifampin. We hypothesize that the clinical response observed is secondary to induction of cytochrome P450 with increased hepatic metabolism of endogenous corticosteroids and a reduction in systemic cortisol levels.

Purpose To evaluate the safety and efficacy of a preoperative intravitreous injection of microplasmin in patients scheduled for vitreous surgery. Design Phase 2, multicenter, placebo-controlled, double-masked, parallel-group, dose-ranging clinical trial. Participants One hundred twenty-five patients scheduled for pars plana vitrectomy (PPV), primarily for treatment of either vitreomacular traction or macular hole. Intervention A single intravitreous injection of either microplasmin at 1 of 3 doses (25 μg, 75 μg, or 125 μg in 100 μl) or placebo injection administered 7 days before PPV. Main Outcome Measures Presence or absence of posterior vitreous detachment (PVD) at the time of PPV, progression of PVD, and resolution of vitreomacular interface abnormality precluding the need for PPV. Results Rates of total PVD at the time of surgery were 10%, 14%, 18%, and 31% in the placebo group (n = 30), 25-μg (n = 29), 75-μg (n = 33), and 125-μg microplasmin groups (n = 32), respectively. The secondary end point resolution of vitreomacular interface abnormality precluding the need for vitrectomy at the 35-day time point was observed at rates of 3%, 10%, 15%, and 31% in the placebo, and the 25-μg, the 75-μg, and the 125-μg microplasmin groups, respectively. At the 180-day time point, the equivalent rates were 3%, 7%, 15%, and 28%, respectively. Conclusions Microplasmin injection at a dose of 125 μg led to a greater likelihood of induction and progression of PVD than placebo injection. Patients receiving microplasmin were significantly more likely not to require vitrectomy surgery. More definitive evaluation in phase 3 clinical trials therefore is warranted. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Objective To evaluate the anatomic and visual outcomes after a surgical procedure for displacement of thick submacular hemorrhage in patients with age-related macular degeneration. Design Retrospective, noncomparative, interventional case series. Participants Twenty-nine consecutive eyes of 28 patients with thick submacular hemorrhage secondary to age-related macular degeneration. Intervention The procedure consisted of a pars plana vitrectomy with subretinal recombinant tissue plasminogen activator injection (125 mg/ml) through a translocation microcannula, followed by fluid–air exchange and postoperative prone positioning. Main outcome measures Intraoperative and postoperative surgical complications, preoperative and postoperative best-corrected visual acuities, postoperative fluorescein angiography results, and additional postoperative treatments. Results Total subfoveal blood displacement was achieved in 25 eyes, with subtotal displacement in the others. Based on fluorescein angiography results, 8 eyes were eligible for additional postoperative treatments. At 3 months, 17 eyes had gained more than 2 lines of visual acuity, whereas 3 had lost more than 2 lines. The difference between preoperative and 3-month postoperative visual acuity was statistically significant ( P = 0.0167). Complications consisted of 2 cases of vitreous hemorrhage that cleared within 4 weeks. Conclusions This surgical technique seems useful in displacing thick submacular hemorrhage secondary to age-related macular degeneration, allowing postoperative fluorescein angiography testing and, potentially, subsequent treatments. No significant complication from the procedure was identified. However, further controlled studies will be required to assess its efficacy in the management of this difficult clinical problem.

Purpose The purpose of the study was to report a unique case that suggests a communication between a colobomatous eye and the orbit. Methods Case report. Patients Eleven-year-old girl. Results Gas moved from the vitreous cavity into the orbit during vitrectomy in a colobomatous microphthalmic eye. Conclusion As this case suggests, there may be an occult connection through the coloboma and the surrounding extraocular tissue, possibly providing an additional etiology of subretinal fluid that can be associated with these congenital optic nerve disorders.

The Age-Related Eye Disease Study (AREDS) was initially conceived as a long-term multicenter, prospective study of the clinical course of age-related macular degeneration (AMD) and age-related cataract. Data on progression rates and risk factors from the study will increase understanding of the clinical course of both conditions, generate hypotheses about etiology, and aid in the design of clinical trials of potential interventions. In addition to collecting natural history data, AREDS includes a clinical trial of high-dose vitamin and mineral supplements for AMD and a clinical trial of high-dose vitamin supplements for cataract. The clinical trials were initiated largely because of the widespread public use in the United States of commercially available pharmacologic doses of vitamins and minerals to treat these two eye conditions and the absence of definitive studies on the safety and efficacy of their use. Important design issues for the clinical trials include: defining cataract and AMD, estimating event rates, determining the type and dosage of vitamins and minerals to be tested for each condition, and identifying the parameters necessary for monitoring safety and efficacy. This paper describes the AREDS design, including the study rationale and operational structure, and the approach adopted to combine, for two diseases, clinical trials with a natural history study. Control Clin Trials 1999;20:573–600

Purpose: The purpose of the study is to assess the hospital charges associated with the treatment of endophthalmitis using a sample of patients from the Endophthalmitis Vitrectomy Study (EVS). Methods: The Endophthalmitis Vitrectomy Study was a multicenter, randomized clinical trial with a two-by-two factorial design to compare immediate pars plana vitrectomy to tap—biopsy and to compare the use of systemic antibiotics (intravenous) to no intravenous antibiotics in the management of postoperative endophthalmitis. Hospital charge data were collected retrospectively from 129 patients from the 4 clinical centers participating in this ancillary study. This represents 31 % of the total Endophthalmitis Vitrectomy Study population. An analysis of variance was used to compare hospital charges across center and treatment. A charge-effectiveness analysis compared measures the effectiveness across treatment groups. The annual savings of hospital charges in the United States was estimated for a range of annual incidence rates of endophthalmitis. Results: The use of intravenous antibiotics significantly increased hospital charges. Patients undergoing vitrectomy had significantly higher hospital charges than did patients undergoing tap—biopsy. The most charge-effective treatment for patients presenting with light perception only vision was immediate vitrectomy, whereas the most charge-effective treatment for patients presenting with better vision was tap—biopsy. Factors other than treatment independently associated with hospital charges were female sex, history of diabetes, symptom of red eye, and baseline vision of light perception only. Conclusions: Assuming the results of the Endophthalmitis Vitrectomy Study were used as a guide for the treatment of endophthalmitis, the estimated annual nationwide reduction of hospital charges would be between $7.6 million and $40.0 million.

Purpose: The authors determine if specific features of the clinical presentation of acute postoperative endophthalmitis correlate with the microbiologic culture results. Methods: A total of 420 patients who had clinical evidence of endophthalmitis within 6 weeks after cataract surgery or secondary intraocular lens implantation were evaluated as part of a randomized clinical trial. Results of cultures performed on aqueous and vitreous specimens obtained at presentation were categorized as follows: gram-positive coagulase-negative micrococci, "other" gram-positive, gram-negative, and equivocal/no growth. Results: Eleven features of the initial clinical presentation were associated with significant differences in the microbiologic spectrum ( P Conclusions: The presenting characteristics of acute endophthalmitis after cataract surgery may be helpful in predicting the most likely culture results. Such predictions do not appear sufficiently strong to guide the initial empiric choice of intravitreal antibiotics.

Myopic macular retinoschisis is a source of visual impairment in patients with high myopia. Many patients present with progressive visual loss or increasing distortion. Some eyes progress to macular hole or foveal retinal detachment, causing further vision loss. The mechanisms for development of myopic macular retinoschisis have been postulated to be from tractional forces exerted on the inner retina, either anteriorly from a shortened internal limiting membrane and the retinal vessels or posteriorly from staphylomatous changes. Surgical intervention is often indicated for patients with declining visual function. The authors report a case of myopic macular retinoschisis that spontaneously improved without surgical intervention. [ Ophthalmic Surg Lasers Imaging Retina . 2013;44:499–501.]

Purpose: To evaluate the efficacy of macular grid photocoagulation in preserving or improving central visual acuity in eyes with macular edema due to central vein occlusion (CVO) and best-corrected visual acuity of 20/50 or poorer. Methods: Patients with angiographically documented macular edema due to CVO were entered into a multicenter randomized controlled clinical trial supported by the National Eye Institute. Eligibility was determined based on both clinical examination findings and photographic documentation evaluated at a photograph reading center. Eyes were assigned randomly to macular grid photocoagulation (77 eyes) or no treatment (78 eyes). Patients were followed every 4 months for 3 years or until the end of the study. The outcome measure was visual acuity. Results: The study population consisted of 155 eyes in 155 patients. There was no difference between treated and untreated eyes in visual acuity at any point during the follow-up period. Initial median visual acuity was 20/160 in treated eyes and 20/ 125 in control eyes. Final median visual acuity was 20/200 in treated eyes and 20/160 in control eyes. However, treatment clearly reduced angiographic evidence of macular edema. Conclusion: The results of this study do not support a recommendation for macular grid photocoagulation for the population meeting the Central Vein Occlusion Study macular edema group eligibility criteria.

Purpose: The purpose of this study is to assess the benefit of vitreous surgery in preventing full-thickness macular holes in patients with impending (stage 1) macular holes. Methods: A prospective randomized multicenter clinical trial was conducted on patients with full-thickness macular holes in their first eye (stage 3 or 4) and signs and symptoms of stage 1 macular holes in their fellow eye (study eye). The study eye was randomized to vitreous surgery or observation. Outcome was assessed by standardized measurement of visual acuity, detailed clinical examination, fundus photographs, and fluorescein angiography. Results: A full-thickness macular hole developed in 10 (37%) of 27 patients in the vitrectomy group compared with 14 (40%) of 35 patients randomized to observation ( P = 0.81). This difference of 3% has a 95% confidence interval of (-21%,27%). Conclusion: The study was terminated because of low recruitment. The authors were unable to prove (or disprove) the benefit of vitreous surgery in patients with stage 1 macular holes. The authors can state, however, that should a beneficial effect from vitrectomy exist, it would probably be minimal. Considering the cost and morbidity of vitreous surgery, a conservative approach for stage 1 macular hole might be appropriate.

The authors report 2-year follow-up information on 179 of 198 eyes (90%) enrolled in a previously published multicenter, randomized, controlled clinical trial comparing pneumatic retinopexy (PR) with scleral buckling (SB) for the management of selected retinal detachments. Scleral buckling was compared with PR with regard to redetachment after the initial 6-month follow-up period (1% versus 1%), overall attachment (98% versus 99%), subsequent cataract surgery (18% versus 4%; P less than 0.05), preoperative visual acuity (no significant difference), and final visual acuity of 20/50 or better in eyes with macular detachment for a period of 14 days or less (67% versus 89%; P less than or equal to 0.05). Reoperations after a failed PR attempt did not adversely affect visual outcome. After 2 years, PR continues to compare favorably with SB.

The materials and techniques for retinal surgery have undergone continued refinement over the past 40 years. This has resulted in a relatively high rate of retinal reattachment. Further understanding of the pathophysiology of retinal detachment together with pharmacologic and instrument advances should contribute to even further success in the future, with even less patient morbidity. Recently, advances in sutureless primary vitrectomy have been introduced. Although these techniques clearly have some advantages, they are unlikely to completely eliminate the need for sutures and excellent suturing technique.

Objective To determine the safety and efficacy of the artificial silicon retina(ASR) microchip implanted in the subretinal space to treat vision loss fromretinitis pigmentosa. Methods The ASR microchip is a 2-mm-diameter silicon-based device that containsapproximately 5000 microelectrode-tipped microphotodiodes and is powered byincident light. The right eyes of 6 patients with retinitis pigmentosa wereimplanted with the ASR microchip while the left eyes served as controls. Safetyand visual function information was collected. Results During follow-up that ranged from 6 to 18 months, all ASRs functionedelectrically. No patient showed signs of implant rejection, infection, inflammation,erosion, neovascularization, retinal detachment, or migration. Visual functionimprovements occurred in all patients and included unexpected improvementsin retinal areas distant from the implant. Main Outcome Measures Subjective improvements included improved perception of brightness,contrast, color, movement, shape, resolution, and visual field size. Conclusions No significant safety-related adverse effects were observed. The observationof retinal visual improvement in areas far from the implant site suggestsa possible generalized neurotrophic-type rescue effect on the damaged retinacaused by the presence of the ASR. A larger clinical trial is indicated tofurther evaluate the safety and efficacy of a subretinally implanted ASR.

To evaluate the anatomic and visual outcomes after a surgical procedure for displacement of thick submacular hemorrhage in patients with age-related macular degeneration.Retrospective, noncomparative, interventional case series.Twenty-nine consecutive eyes of 28 patients with thick submacular hemorrhage secondary to age-related macular degeneration.The procedure consisted of a pars plana vitrectomy with subretinal recombinant tissue plasminogen activator injection (125 micrograms/ml) through a translocation microcannula, followed by fluid-air exchange and postoperative prone positioning [correction].Intraoperative and postoperative surgical complications, preoperative and postoperative best-corrected visual acuities, postoperative fluorescein angiography results, and additional postoperative treatments.Total subfoveal blood displacement was achieved in 25 eyes, with subtotal displacement in the others. Based on fluorescein angiography results, 8 eyes were eligible for additional postoperative treatments. At 3 months, 17 eyes had gained more than 2 lines of visual acuity, whereas 3 had lost more than 2 lines. The difference between preoperative and 3-month postoperative visual acuity was statistically significant (P = 0.0167). Complications consisted of 2 cases of vitreous hemorrhage that cleared within 4 weeks.This surgical technique seems useful in displacing thick submacular hemorrhage secondary to age-related macular degeneration, allowing postoperative fluorescein angiography testing and, potentially, subsequent treatments. No significant complication from the procedure was identified. However, further controlled studies will be required to assess its efficacy in the management of this difficult clinical problem.

Experimental and observational data suggest that micronutrients with antioxidant capabilities may retard the development of age-related cataract.To evaluate the effect of a high-dose antioxidant formulation on the development and progression of age-related lens opacities and visual acuity loss.The 11-center Age-Related Eye Disease Study (AREDS) was a double-masked clinical trial. Participants were randomly assigned to receive daily oral tablets containing either antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg) or no antioxidants. Participants with more than a few small drusen were also randomly assigned to receive tablets with or without zinc (80 mg of zinc as zinc oxide) and copper (2 mg of copper as cupric oxide) as part of the age-related macular degeneration trial. Baseline and annual (starting at year 2) lens photographs were graded at a reading center for the severity of lens opacities using the AREDS cataract grading scale.Primary outcomes were (1) an increase from baseline in nuclear, cortical, or posterior subcapsular opacity grades or cataract surgery, and (2) at least moderate visual acuity loss from baseline (/=15 letters). Primary analyses used repeated-measures logistic regression with a statistical significance level of P =.01. Serum level measurements, medical histories, and mortality rates were used for safety monitoring.Of 4757 participants enrolled, 4629 who were aged from 55 to 80 years had at least 1 natural lens present and were followed up for an average of 6.3 years. No statistically significant effect of the antioxidant formulation was seen on the development or progression of age-related lens opacities (odds ratio = 0.97, P =.55). There was also no statistically significant effect of treatment in reducing the risk of progression for any of the 3 lens opacity types or for cataract surgery. For the 1117 participants with no age-related macular degeneration at baseline, no statistically significant difference was noted between treatment groups for at least moderate visual acuity loss. No statistically significant serious adverse effect was associated with treatment.Use of a high-dose formulation of vitamin C, vitamin E, and beta carotene in a relatively well-nourished older adult cohort had no apparent effect on the 7-year risk of development or progression of age-related lens opacities or visual acuity loss.

To the Editor. —The surgical treatment of patients with macular pucker from epiretinal membrane formation has become increasingly common with the advent of new vitreoretinal techniques. Typically, after vitrectomy is performed, an edge of the epiretinal tissue is elevated with a bent needle or membrane pick, enabling the membrane to be grasped and removed with forceps. It is often difficult to identify an accessible membrane edge, particularly in patients with idiopathic epiretinal membranes, and intraoperative complications, such as bleeding and/or creation of retinal tears, can occur. We recently used an alternative technique to facilitate the elevation and removal of epiretinal tissue in our patients with idiopathic epiretinal membranes. Surgical Technique. —A standard three-port vitrectomy setup is used. Deep vitrectomy is performed, with the complete removal of all formed vitreous over the posterior pole. A 20-gauge soft-tipped extrusion cannula (Model 149.52, Grieshaber, Schaffhausen, Switzerland) is introduced just over the surface of

Observational and experimental data suggest that antioxidant and/or zinc supplements may delay progression of age-related macular degeneration (AMD) and vision loss.To evaluate the effect of high-dose vitamins C and E, beta carotene, and zinc supplements on AMD progression and visual acuity.The Age-Related Eye Disease Study, an 11-center double-masked clinical trial, enrolled participants in an AMD trial if they had extensive small drusen, intermediate drusen, large drusen, noncentral geographic atrophy, or pigment abnormalities in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye. At least 1 eye had best-corrected visual acuity of 20/32 or better. Participants were randomly assigned to receive daily oral tablets containing: (1) antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg); (2) zinc, 80 mg, as zinc oxide and copper, 2 mg, as cupric oxide; (3) antioxidants plus zinc; or (4) placebo.(1) Photographic assessment of progression to or treatment for advanced AMD and (2) at least moderate visual acuity loss from baseline (or =15 letters). Primary analyses used repeated-measures logistic regression with a significance level of.01, unadjusted for covariates. Serum level measurements, medical histories, and mortality rates were used for safety monitoring.Average follow-up of the 3640 enrolled study participants, aged 55-80 years, was 6.3 years, with 2.4% lost to follow-up. Comparison with placebo demonstrated a statistically significant odds reduction for the development of advanced AMD with antioxidants plus zinc (odds ratio [OR], 0.72; 99% confidence interval [CI], 0.52-0.98). The ORs for zinc alone and antioxidants alone are 0.75 (99% CI, 0.55-1.03) and 0.80 (99% CI, 0.59-1.09), respectively. Participants with extensive small drusen, nonextensive intermediate size drusen, or pigment abnormalities had only a 1.3% 5-year probability of progression to advanced AMD. Odds reduction estimates increased when these 1063 participants were excluded (antioxidants plus zinc: OR, 0.66; 99% CI, 0.47-0.91; zinc: OR, 0.71; 99% CI, 0.52-0.99; antioxidants: OR, 0.76; 99% CI, 0.55-1.05). Both zinc and antioxidants plus zinc significantly reduced the odds of developing advanced AMD in this higher-risk group. The only statistically significant reduction in rates of at least moderate visual acuity loss occurred in persons assigned to receive antioxidants plus zinc (OR, 0.73; 99% CI, 0.54-0.99). No statistically significant serious adverse effect was associated with any of the formulations.Persons older than 55 years should have dilated eye examinations to determine their risk of developing advanced AMD. Those with extensive intermediate size drusen, at least 1 large druse, noncentral geographic atrophy in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye, and without contraindications such as smoking, should consider taking a supplement of antioxidants plus zinc such as that used in this study.

Objectives. —This report presents information on the effects of aspirin on mortality, the occurrence of cardiovascular events, and the incidence of kidney disease in the patients enrolled in the Early Treatment Diabetic Retinopathy Study (ETDRS). Study Design. —This multicenter, randomized clinical trial of aspirin vs placebo was sponsored by the National Eye Institute. Patients. —Patients (N=3711) were enrolled in 22 clinical centers between April 1980 and July 1985. Men and women between the ages of 18 and 70 years with a clinical diagnosis of diabetes mellitus were eligible. Approximately 30% of all patients were considered to have type I diabetes mellitus, 31% type II, and in 39% type I or II could not be determined definitely. Intervention. —Patients were randomly assigned to aspirin or placebo (two 325-mg tablets once per day). Main Outcome Measures. —Mortality from all causes was specified as the primary outcome measure for assessing the systemic effects of aspirin. Other outcome variables included cause-specific mortality and cardiovascular events. Results. —The estimate of relative risk for total mortality for aspirin-treated patients compared with placebo-treated patients for the entire study period was 0.91 (99% confidence interval, 0.75 to 1.11). Larger differences were noted for the occurrence of fatal and nonfatal myocardial infarction; the estimate of relative risk was 0.83 for the entire follow-up period (99% confidence interval, 0.66 to 1.04). Conclusions. —The effects of aspirin on any of the cardiovascular events considered in the ETDRS were not substantially different from the effects observed in other studies that included mainly nondiabetic persons. Furthermore, there was no evidence of harmful effects of aspirin. Aspirin has been recommended previously for persons at risk for cardiovascular disease. The ETDRS results support application of this recommendation to those persons with diabetes at increased risk of cardiovascular disease. (JAMA. 1992;268:1292-1300)

• Propofol is an intravenous anesthetic agent that was approved by the US Food and Drug Administration in October 1989. It has gained rapid acceptance and is in widespread use. In June 1990, the Centers for Disease Control reported four clusters of postsurgical infections associated with the use of propofol. We describe one of those clusters, consisting of four cases of endogenous Candida albicans endophthalmitis. These infections occurred in nonimmunocompromised patients after they had undergone nonophthalmologic surgery in which propofol had been used as anesthesia. An investigation by the Centers for Disease Control concluded that the infections in these patients were due to extrinsic contamination of propofol during preparation for use at the hospital. Ophthalmologists should be aware of this new potential source of endogenous endophthalmitis.

A major cause for failure of krypton red laser photocoagulation in patients with exudative age-related macular degeneration has been the development of recurrent choroidal neovascularization adjacent to the previously treated areas. After reviewing the possible causes of recurrences, it is apparent that a certain number are iatrogenic, ie, induced by krypton red laser causing disruption and damage to the pigment epithelium-Bruch's membrane-choroidal complex. We describe three separate episodes in two patients of iatrogenic recurrent choroidal neovascularization after krypton red laser photocoagulation.

Pneumatic retinopexy was compared with scleral buckling in a multicenter (7 centers), randomized, controlled, clinical trial with 198 patients. Admission criteria included detachments with retinal break(s) no greater than 1 clock hour in size, within the superior two thirds of the fundus, without significant proliferative vitreoretinopathy (PVR). All patients were followed for at least 6 months. Scleral buckling was compared with pneumatic retinopexy with regard to single-operation reattachment (82 versus 73%), reattachment with one operation and postoperative laser/cryotherapy (84 versus 81 %), overall reattachment with reoperations (98 versus 99%), final visual acuity of 20/50 or better in eyes with preoperative detachment of the macula for 2 weeks or less (56 versus 80%), PVR (5 versus 3%), and new retinal breaks (13 versus 23%). Complications, including reoperations, as measured by the "score" system, were similar. The anatomic results of the two operations were not significantly different ( P > 0.05), but pneumatic retinopexy had less morbidity and better postoperative visual acuity ( P = 0.01). Pneumatic retinopexy is recommended for cases meeting the admission criteria.

The authors describe in seven eyes of four patients a form of serpiginous choroiditis beginning in the macula without initial peripapillary activity. Eyes with macular serpiginous choroiditis often had a poor visual prognosis and sometimes developed subretinal neovascularization. Fluorescein angiography of the acute lesions showed hypofluorescence; some cases were thus initially diagnosed as having choroidal ischemia. Fluorescein angiography in one eye, however, suggested that at least some of the hypofluorescence seen acutely in eyes with serpiginous choroiditis is secondary to blocked fluorescence from "opaque" retinal pigment epithelium.

We examined nine patients in whom retinal tacks intruded into the eye and lodged in the subretinal space, preretinal space, vitreous cavity, or anterior chamber. Complications included retinal pigment epithelium atrophy; retinal phlebitis; vitreous hemorrhage; focal corneal, iris, and retinal injury; and corneal edema. The intrusion of the retinal tacks did not apparently cause, but was associated with retinal redetachment in five patients. Factors associated with intrusion of the retinal tacks included (1) absence of a barb at the end of the tack to anchor it to the sclera, (2) absence of a groove in the tack, (3) a short shaft, (4) incomplete penetration of the retina, choroid, and sclera by the tack, (5) self-inflicted trauma to the eye, (6) placing a scleral buckle after inserting the tacks, and (7) reproliferation of periretinal membranes. In four patients the intruded tacks did not cause any complications. In four patients the intruded tacks were removed without complications and in the remaining five patients, they were left in the eye.