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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: To determine whether propranolol can decrease surgical tremor and anxiety in residents performing ocular microsurgery without impairing patient or physician safety. METHODS: In this randomized, double-masked, crossover study, 5 third-year ophthalmology residents ingested a capsule containing either propranolol, 40 mg, or placebo 1 hour prior to performing ophthalmic microsurgery. All residents were healthy men under age 30 years. Prior to commencement of the study, all participants had successfully been administered a test dose of propranolol without side effects. The study took place over a 10-week period. At the conclusion of each case, both the resident and attending surgeon observer independently completed a form grading, on a sliding scale: (1) amount of overall tremor; (2) amount of tremor during placement of the first 3 sutures after lens or nucleus extraction; (3) anticipated difficulty of the case; (4) actual difficulty with the case; and (5) anxiety (surgeon only). In addition, the type of procedure performed, complications encountered, and surgeon side effects were recorded. The data were analyzed with a 2-way analysis of variance for unbalanced data. RESULTS: A total of 73 surgical cases were performed; the surgeons were administered propranolol for 40 cases and placebo for 33. As judged by the resident surgeon, there was a highly significant effect of propranolol in decreasing anxiety (P = .0058), reducing surgical tremor overall (P < .0001), and reducing tremor while placing the first 3 sutures following lens extraction (P < .0001). There was no treatment-by-surgeon interaction for any of the measures. Complications and difficulty of the case, as judged by both the resident and attending surgeons, were not significantly different in the propranolol versus placebo groups (P > .05). There were no side effects reported or observed in any of the surgeons. CONCLUSIONS: Propranolol, 40 mg, administered 1 hour prior to surgery, significantly decreases tremor and anxiety in the surgeon without untoward effects to the surgeon and the patient. However, it is unknown whether decreased tremor and anxiety improved surgical outcome.

OBJECTIVE: To evaluate the feasibility of conducting a randomized, controlled trial of thrombolytic therapy for central retinal vein occlusion (CRVO) using tissue plasminogen activator (TPA); to establish relative efficacy and safety of various dosing regimens. DESIGN AND PATIENTS: Ninety-six patients with CRVO were treated with TPA between May 1986 and December 1992. Prior to patient enrollment, a standardized, detailed protocol was developed for evaluation and treatment of all patients. This included standard protocols for determining eligibility, reporting complications, performing photography and electroretinography, and measuring visual acuity. MAIN OUTCOME MEASURES: Best corrected visual acuity at 6 months, systemic and ophthalmic treatment complications. RESULTS: At 6 months' follow-up, 42% (n = 89) of eyes gained three or more lines of vision from pretreatment levels (average gain, 5.1 lines), 37% remained stable, and 21% lost three or more lines. Of eyes with 20/100 or worse pretreatment vision (n = 32), 59% gained three or more lines vision (average gain, 6.4 lines), 31% remained stable, and 9% lost three or more lines. One patient suffered a fatal stroke. Three patients developed intraocular bleeding during TPA administration. CONCLUSION: Thromobolytic therapy with TPA appears to be a promising, albeit risky, new treatment; conclusive evaluation of safety and efficacy awaits a multicenter, randomized, clinical trial; feasibility of such a trial has been established by this study.

A posterior staphyloma is characterised by scleral ectasia and is pathognomonic for pathological myopia.1,2 Posterior staphylomas are classified in to five types based on the anatomic location.1 Type 1 staphylomas extend from the nasal border of the optic nerve into the macular region and are the most frequent staphyloma seen in myopes.1 Type 2 staphylomas are centred on the macula while type 3 staphylomas are centred on the optic disc without macular extension.1 Type 4 staphylomas are located nasal to the optic disc and type 5 staphylomas develop inferior to the optic disc.1 Staphylomas can be associated with multiple complications including retinal pigment epithelial atrophy, lacquer cracks, retinal and subretinal haemorrhages, and choroidal neovascularisation.1,3 This report describes a patient with undiagnosed, bilateral type 2 macular staphylomas compounded by cone dystrophy. To the best of our knowledge, this is a novel association not reported in the literature and with potential therapeutic implications. A 32 year old white woman presented to the Wilmer Ophthalmological Institute, Baltimore, MD, for a second opinion. She …

Three patients developed cellulitis and skin necrosis following fluorescein dye extravasation. This experience prompted a survey of the Macula Society membership to determine whether this complication of fluorescein angiography is as rare as the paucity of cases in the literature suggests. In addition, the manufacturer was asked to reexamine the dye lot to determine whether an impurity had been introduced unintentionally during the manufacturing process. No impurity was found in the dye lots tested. The survey disclosed only nine additional cases of skin necrosis, leading to the conclusion that skin necrosis probably represents a rare, idiosyncratic reaction. Although fluorescein angiography remains a safe procedure, efforts should be directed toward prevention of dye extravasation. When extravasation does occur, prompt and proper medical attention with close follow-up study may minimize the likelihood of skin necrosis.

Cystoid macular edema frequently complicates recovery from cataract surgery. Our understanding of this disease would be enhanced by more sensitive and quantitative methods to evaluate it. We performed vitreous fluorophotometry in 66 nondiabetic patients who had recently undergone cataract surgery. Eyes with definite macular edema on fluorescein angiography were ranked according to the severity of the leakage. The rank of the leakage correlated significantly with the vitreous fluorophotometry values (P less than 0.01). The mean fluorophotometry result in the eyes with cystoid macular edema was greater than that in the phakic, control group (P less than 0.01). However, eyes with minimal or no leakage visible on fluorescein angiography had fluorophotometry values indistinguishable from normal. The quantitative vitreous fluorophotometry results provided an indicator of cystoid macular edema that may prove useful in following this problem and evaluating therapy for it.

The Macular Photocoagulation Study (MPS) Fundus Photograph Reading Center has developed a standard set of methods for assessing color photographs and fluorescein angiograms on study patients. For pretreatment angiograms, these methods are used to determine the location and extent of the choroidal neovascularization. For posttreatment color fundus photographs, these methods are used to assess the extent and intensity of treatment. Although these methods were developed to judge eligibility and treatment of patients enrolled in the MPS, they provide an excellent way for all treating ophthalmologists to evaluate their patients' angiograms and to assess immediately the intensity and extent of laser photocoagulation. The technique requires a microfilm reader or slide projection device to determine the completeness of treatment. The authors superimpose independent drawings made from pre- and posttreatment photographs. The techniques described can be applied readily in clinical practice. Since persistent neovascularization is highly correlated with incomplete and/or inadequate photocoagulation treatment, clinicians may adopt these Reading Center techniques to minimize the frequency of persistent neovascularization and, possibly, to reduce the frequency of visual loss in treated eyes.

Seven diabetic patients experienced severe but transient visual loss after panretinal photocoagulation for proliferative diabetic retinopathy. In all patients, visual acuity decreased shortly after treatment to levels ranging from 5/200 to no light perception. In five of the patients, no observable ocular disease or surgical complications could explain the degree of visual loss. The other two patients developed exudative macular detachments, although it was not clear that this change accounted for their severe visual loss. Vision improved in all patients over a period ranging from nine days to nine months. In five patients, visual acuity returned to within two Snellen lines of the pretreatment level.