A recent Pediatric Eye Disease Investigator Group article demonstrates that treatment of amblyopia with weekend atropine provides the same level of improvement as daily atropine.1Pediatric Eye Disease Investigator GroupA randomized trial of atropine regimens for treatment of moderate amblyopia in children.Ophthalmology. 2004; 111: 2076-2085Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar It was previously shown that atropine occlusion is equivalent to patching2Pediatric Eye Disease Investigator GroupA randomized trial of atropine vs. patching for treatment of moderate amblyopia in children.Arch Ophthalmol. 2002; 120: 268-278Crossref PubMed Scopus (427) Google Scholar and that 6 hours of patching is equivalent to 2 hours of daily patching.3Repka M.K. Beck R.W. Holmes J.M. et al.Pediatric Eye Disease Investigator GroupA randomized trial of patching regimens for treatment of moderate amblyopia in children.Arch Ophthalmol. 2003; 121: 603-611Crossref PubMed Scopus (340) Google Scholar It remains necessary to certify that the treatment protocols are more effective than a placebo. Although the authors “did not believe that [they] feasibly could include an untreated control group,”1Pediatric Eye Disease Investigator GroupA randomized trial of atropine regimens for treatment of moderate amblyopia in children.Ophthalmology. 2004; 111: 2076-2085Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar it would have been possible, for example, to add in a group treated only with a short-acting cycloplegic. “Clinical research must be designed and conducted with rigorous methodology to generate reliable and valid data. A placebo control must be required to optimize the chance of achieving a valid test or treatment efficacy.”4Miller F.G. Emanuel E.J. Rosenstein D.L. Straus S.E. Ethical issues concerning research in complementary and alternative medicine.JAMA. 2004; 291: 599-604Crossref PubMed Scopus (95) Google Scholar This concept was recently reaffirmed in the ophthalmic literature.5Beck R.W. Reporting the results of randomized clinical trials a priority of Archives of Ophthalmology.Arch Ophthalmol. 2004; 122: 1038-1039Crossref PubMed Scopus (1) Google Scholar Amblyopia studies should not be exempted from these basic requirements. It would be helpful for future studies of amblyopia treatment to comply with accepted standards of clinical research. Atropine Regimens for Amblyopia: Author replyOphthalmologyVol. 112Issue 8PreviewWe disagree with Dr Lempert’s comment with regard to our methodology. The randomized trials conducted by the Pediatric Eye Disease Investigator Group follow well-accepted clinical trial methodology. In a randomized clinical trial, a control group may be assigned standard care rather than a placebo. In this specific amblyopia treatment trial, the daily atropine group was the control group, which was compared with the weekend-only atropine group. Before initiation of a Pediatric Eye Disease Investigator Group study, every protocol is reviewed and approved by an independent National Eye Institute-appointed panel of experts that includes statisticians and clinical trialists. Full-Text PDF

BACKGROUND:To plan a future randomized clinical trial, we conducted a pilot study to determine whether children randomized to near or non-near activities would perform prescribed activities. A secondary aim was to obtain a preliminary estimate of the effect of near versus non-near activities on amblyopic eye visual acuity, when combined with 2 hours of daily patching.METHODS:Sixty-four children, 3 to less than 7 years of age, with anisometropic, strabismic, or combined amblyopia (20/40 to 20/400) were randomly assigned to receive either 2 hours of daily patching with near activities or 2 hours of daily patching without near activities. Parents completed daily calendars for 4 weeks recording the activities performed while patched and received a weekly telephone call in which they were asked to describe the activities performed during the previous 2 hours of patching. Visual acuity was assessed at 4 weeks.RESULTS:The children assigned to near visual activities performed more near activities than those assigned to non-near activities (by calendars, mean 1.6 +/- 0.5 hours versus 0.2 +/- 0.2 hours daily, P < 0.001; by telephone interviews, 1.6 +/- 0.4 hours versus 0.4 +/- 0.5 hours daily, P < 0.001). After 4 weeks of treatment, there was a suggestion of greater improvement in amblyopic eye visual acuity in those assigned to near visual activities (mean 2.6 lines versus 1.6 lines, P = 0.07). The treatment group difference in visual acuity was present for patients with severe amblyopia but not moderate amblyopia.CONCLUSIONS:Children patched and instructed to perform near activities for amblyopia spent more time performing those near activities than children who were instructed to perform non-near activities. Our results suggest that performing near activities while patched may be beneficial in treating amblyopia. Based on our data, a formal randomized amblyopia treatment trial of patching with and without near activities is both feasible and desirable.

We disagree with Dr Lempert’s comment with regard to our methodology. The randomized trials conducted by the Pediatric Eye Disease Investigator Group follow well-accepted clinical trial methodology. In a randomized clinical trial, a control group may be assigned standard care rather than a placebo. In this specific amblyopia treatment trial, the daily atropine group was the control group, which was compared with the weekend-only atropine group. Before initiation of a Pediatric Eye Disease Investigator Group study, every protocol is reviewed and approved by an independent National Eye Institute-appointed panel of experts that includes statisticians and clinical trialists. In addition, Dr Lempert inaccurately cites the Archives of Ophthalmology editorial written by one of us (RWB).1Beck R.W. Reporting the results of randomized clinical trials a priority of Archives of Ophthalmology.Arch Ophthalmol. 2004; 122: 1038-1039Crossref PubMed Scopus (1) Google Scholar The importance of randomization in clinical trials is emphasized, but the editorial does not address the issue of placebo controls and when they are needed. Atropine Regimens for AmblyopiaOphthalmologyVol. 112Issue 8PreviewA recent Pediatric Eye Disease Investigator Group article demonstrates that treatment of amblyopia with weekend atropine provides the same level of improvement as daily atropine.1 It was previously shown that atropine occlusion is equivalent to patching2 and that 6 hours of patching is equivalent to 2 hours of daily patching.3 Full-Text PDF

OBJECTIVE:To compare patching and atropine sulfate as treatments for moderate amblyopia in children 18 months after completion of a 6-month randomized trial.METHODS:In a randomized, multicenter (47 sites) clinical trial, 419 children younger than 7 years with amblyopia (20/40 to 20/100 in the affected eye) were assigned to receive either patching or atropine eye drops for 6 months. Between 6 months and 2 years, treatment was at the discretion of the investigator. Main Outcome Measure Visual acuity in the amblyopic eye and sound eye after 2 years.RESULTS:At 2 years, visual acuity in the amblyopic eye improved from baseline a mean of 3.7 lines in the patching group and 3.6 lines in the atropine group. The difference in visual acuity between treatment groups was small: 0.01 logMAR (95% confidence interval, -0.02 to 0.04). In both treatment groups, the mean amblyopic eye acuity was approximately 20/32, 1.8 lines worse than the mean sound eye acuity, which was approximately 20/20.CONCLUSIONS:Atropine or patching for 6 months followed by best clinical care until 2 years produced similar improvement of moderate amblyopia in children between 3 and 7 years of age at enrollment. However, on average the amblyopic eye acuity was still approximately 2 lines worse than the sound eye.

Objective: To determine whether earlier treatment using ablation of the avascular retina in high-risk prethreshold retinopathy of prematurity (ROP) results in improved grating visual acuity and retinal structural outcomes compared with conventional treatment.Methods: Infants with bilateral high-risk prethreshold ROP (n=317) had one eye randomized to early treatment with the fellow eye managed conventionally (control eye). in asymmetric cases (n=84), the eye with high-risk prethreshold ROP was randomized to early treatment or conventional management. High risk was determined using a model based on the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity natural history cohort. At a corrected age of 9 months, visual acuity was assessed by masked testers using the Teller acuity card procedure. At corrected ages of 6 and 9 months, eyes were examined for structural outcome. Outcomes for the 2 treatment groups of eyes were compared using chi(2) analysis, combining data for bilateral and asymmetric cases.Results: Grating acuity results showed a reduction in unfavorable visual acuity outcomes with earlier treatment, from 19.5% to 14.5% (P=.01). Unfavorable structural outcomes were reduced from 15.6% to 9.1% (P<.001) at 9 months. Further analysis supported retinal ablative therapy for eyes with type I ROP, defined as zone I, any stage ROP with plus disease (a degree of dilation and tortuosity of the posterior retinal blood vessels meeting or exceeding that of a standard photograph); zone I, stage 3 ROP without plus disease; or zone II, stage 2 or 3 ROP with plus disease. The analysis supported a wait-and-watch approach to type 2 ROP, defined as zone I, stage I or 2 ROP without plus disease or zone II, stage 3 ROP without plus disease. These eyes should be considered for treatment only if they progress to type I or threshold ROP.Conclusions: Early treatment of high-risk prethreshold ROP significantly reduced unfavorable outcomes to a clinically important degree. Additional analyses led to modified recommendations for the use of peripheral retinal ablation in. eyes with ROP. Long-term follow-up is being conducted to learn whether the benefits noted in the first year after birth will persist into childhood.

Clinical trials have served as the foundation of much of the knowledge we have gained in the last 50 years with regard to the efficacy of treatments of various medical conditions. In very few conditions is the natural history of the disease so well defined, and the outcome of intervention so evident, that the benefits and adverse effects of a treatment can be determined without a prospective, controlled trial. Sometimes trial results confirm clinical impressions, and sometimes they do not. Drs von Noorden and Campos indicate that in their experience full-time patching produces better results than part-time patching in treating severe amblyopia. However, they provide no data to support this conclusion, and we are not aware of a prospective study that supports this claim. They indicate that, for most clinicians, full-time patching has been the standard of care for severe amblyopia. Nevertheless, whether to prescribe full-time or part-time patching for severe amblyopia is a controversy recently reported in the literature1Tan J.H Thompson J.R Gottlob I Differences in management of amblyopia between European countries.Br J Ophthalmol. 2003; 87: 291-296Crossref PubMed Scopus (25) Google Scholar and confirmed by a survey of our investigator group in 1998. Drs von Noorden and Campos state that “children who wear their patch only part of the prescribed time do not respond as well to treatment,” citing studies that report the response to patching, as a function of compliance, and measured by an occlusion dose monitor.2Loudon S.E Polling J.R Simonsz H.J A preliminary report about the relation between visual acuity increase and compliance in patching therapy for amblyopia.Strabismus. 2002; 10: 79-82Crossref PubMed Scopus (49) Google Scholar, 3Loudon S.E Polling J.R Simonsz H.J Electronically measured compliance with occlusion therapy for amblyopia is related to visual acuity increase.Graefes Arch Clin Exp Ophthalmol. 2003; 241: 176-180Crossref PubMed Scopus (71) Google Scholar In these studies, 14 children were prescribed a wide range of part-time occlusion regimens (from 15 minutes a day to 3 complete days per week) for a wide range of amblyopia severity (0.78 [20/25]–0.03 [20/667]). We question whether these data are useful in addressing the issue of part-time versus full time patching in severe amblyopia. In addition, any analysis of clinical trial data limited to compliant patients has considerable potential for bias and production of erroneous conclusions, particularly in a condition such as amblyopia, in which the response to treatment may influence subsequent compliance. There are examples in the literature of erroneous conclusions drawn from selected compliant populations.4Chene G Morlat P Leport C et al.Intention-to-treat vs. on-treatment analyses of clinical trial data experience from a study of pyrimethamine in the primary prophylaxis of toxoplasmosis in HIV-infected patients.Control Clin Trials. 1998; 19: 233-248Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar, 5The Coronary Drug Project Research GroupInfluence of adherence to treatment and response of cholesterol on mortality in the Coronary Drug Project.N Engl J Med. 1980; 303: 1038-1041Crossref PubMed Scopus (663) Google Scholar Drs von Noorden and Campos contend that a treatment group difference might have become apparent with longer follow up. In designing the trial, the 4-month follow-up period represented the maximum length of time we believed that the fixed treatment regimens (6 hours/day or full-time patching) could be prescribed before a change in the treatment might be necessary for patients who had not responded well to the randomized treatment assignment. It is conceivable that treating for longer might show greater benefit with full-time than part-time patching, although there is no suggestion of even a trend in our data favoring a delayed benefit for full-time patching comparing our results at 5 weeks with our results at 4 months. As noted by Drs von Noorden and Campos, we state that our study compared prescribed patching regimens and not the actual number of hours of occlusion that were achieved. We commented in the “Discussion” that it is possible that the results reflect, at least in part, suboptimal compliance in the full-time patching group. However, we designed this trial to assess the effectiveness of the prescribed patching regimens rather than their efficacy. Efficacy refers to whether a treatment has benefit under highly controlled conditions, whereas effectiveness refers to whether a treatment has benefit as used in the real world. A greater number of hours of actual patching could have greater efficacy than fewer hours, but if this intensity of patching can only be achieved in a minority of cases, it would not be a very effective treatment. Our compliance data suggest that most patients are not able to achieve full-time patching, so although it is of scientific interest as to whether full-time occlusion can produce a better outcome than part-time occlusion, this may have limited clinical utility. We have not yet studied the potential benefit of full-time patching in patients who have had an incomplete response to part-time patching, but our data suggest it is entirely reasonable to prescribe an initial course of part-time occlusion for severe amblyopia. In response to Dr Greenberg's comments, the inclusion of multiple community-based sites, rather than limiting a trial to tertiary referral centers, has the advantage of enhancing generalizability of the results. The type of patient enrolled in this study, with severe anisometropic or strabismic amblyopia and no patching during the preceding 6 months, was seen much more commonly at our community-based sites than at our institution-based sites. Including multiple community-based centers in the trial design is not unorthodox, but is a priority for future clinical trials funded by the National Institutes of Health, according to its director.6Re-engineering the clinical research enterprise. Available at: http://www.nihroadmap.nih.gov/clinicalresearch/index.asp. Accessed January 13, 2004Google Scholar As a rule, it is highly inaccurate to extrapolate from an individual's recollection of his or her own practice to the number of patients that can be recruited for a randomized clinical trial with strict inclusion criteria such as severe anisometropic or strabismic amblyopia and no patching during the preceding 6 months. Clinical trialists often use 50% or even 10% of the number cited by individual investigators before a study when considering feasibility of recruitment. As noted above, a substantial proportion of pediatric eye care providers prescribed part-time patching for severe amblyopia before the initiation of our study. Many eye care providers request that the child perform some activities at near requiring visual attention for some of the time the patch is worn. Because, as noted by Dr Greenberg, it is not known whether performing near activities influences the response to occlusion therapy, this was included in the protocol in both groups to standardize that aspect of the treatment regimens. We will be conducting a future trial to determine whether near activities are beneficial during patching. Dr Greenberg provides a single case report to refute our findings. Of interest, in the occlusion dose monitor studies cited earlier,2Loudon S.E Polling J.R Simonsz H.J A preliminary report about the relation between visual acuity increase and compliance in patching therapy for amblyopia.Strabismus. 2002; 10: 79-82Crossref PubMed Scopus (49) Google Scholar, 3Loudon S.E Polling J.R Simonsz H.J Electronically measured compliance with occlusion therapy for amblyopia is related to visual acuity increase.Graefes Arch Clin Exp Ophthalmol. 2003; 241: 176-180Crossref PubMed Scopus (71) Google Scholar there was one patient with severe strabismic amblyopia and an initial visual acuity (VA) of 20/200 who improved to 20/25 with only 1 hour of patching per day. We do not believe that a conclusion should be drawn from the latter case, that little patching improves severe amblyopia, any more than a conclusion should be drawn from Dr Greenberg's case that full-time patching is needed to treat successfully every case of severe amblyopia. Disparate results in case reports and case series point to the critical importance of prospective, randomized trials for providing meaningful, clinically relevant information for establishing treatment guidelines. Randomization reduces the potential selection bias to which Dr Greenberg refers. Complete masking of all outcome measurements is rarely obtainable in clinical trials, and >90% masking would be considered excellent. In our study, the VA outcome was measured using a highly automated, computerized, VA testing protocol, where there was little opportunity for even a biased nonmasked tester to influence the results.7Holmes J.M Beck R.W Repka M.X et al.The Amblyopia Treatment Study visual acuity testing protocol.Arch Ophthalmol. 2001; 119: 1345-1353Crossref PubMed Scopus (257) Google Scholar, 8Moke P.S Turpin A.H Beck R.W et al.Computerized method of visual acuity testing; adaptation of the Amblyopia Treatment Study visual acuity testing protocol.Am J Ophthalmol. 2001; 132: 903-909Abstract Full Text Full Text PDF PubMed Scopus (202) Google Scholar We believe that our trial of 175 patients provides the best evidence available to date on the response of severe amblyopia to different prescribed patching regimens. We contend that our study was conducted with a high degree of rigor and that the validity of the results are comparable to that of any other trial funded by the National Eye Institute, including the 2 trials Dr Greenberg mentions. Perhaps Dr Greenberg will be reassured in knowing that an independent data and safety monitoring committee (Drs Barlow, Buckley, Davis, Dobson, Keltner, Osman, Palmer, and Phelps—see article for listing of full names and affiliations) appointed by the National Eye Institute approved the protocol before its initiation, monitored the data during the conduct of the trial, reviewed the results at the end of the trial, and approved the manuscript before its submission to Ophthalmology. The Pediatric Eye Disease Investigator Group, which conducted this trial, remains open to new investigators. We would welcome the involvement of Dr Greenberg and others with busy pediatric eye care practices. For information on becoming an investigator in the Pediatric Eye Disease Investigator Group, please contact the Pediatric Eye Disease Investigator Group Coordinating Center at [email protected].

BACKGROUND:Although amblyopia can be successfully treated with patching or atropine, there have been few prospective studies of amblyopia recurrence once treatment is discontinued.METHODS:We enrolled 156 children with successfully treated anisometropic or strabismic amblyopia (145 completed follow-up), who were younger than 8 years of age and who received continuous amblyopia treatment for the previous 3 months (prescribed at least 2 hours of daily patching or prescribed at least one drop of atropine per week) and who had improved at least 3 logMAR levels during the period of continuous treatment. Patients were followed off treatment for 52 weeks to assess recurrence of amblyopia, defined as a 2 or more logMAR level reduction of visual acuity from enrollment, confirmed by a second examination. Recurrence was also considered to have occurred if treatment was restarted because of a nonreplicated 2 or more logMAR level reduction of visual acuity.RESULTS:Recurrence occurred in 35 (24%) of 145 cases (95% confidence interval 17% to 32%) and was similar in patients who stopped patching (25%) and in patients who stopped atropine (21%). In patients treated with moderately intense patching (6 to 8 hours per day), recurrence was more common (11 of 26; 42%) when treatment was not reduced prior to cessation than when treatment was reduced to 2 hours per day prior to cessation (3 of 22; 14%, odds ratio 4.4, 95% confidence interval 1.0 to 18.7).CONCLUSIONS:Approximately one fourth of successfully treated amblyopic children experience a recurrence within the first year off treatment. For patients treated with 6 or more hours of daily patching, our data suggest that the risk of recurrence is greater when patching is stopped abruptly rather than when it is reduced to 2 hours per day prior to cessation. A randomized clinical trial of no weaning versus weaning in successfully-treated amblyopia is warranted to confirm these observational findings.

OBJECTIVE To evaluate outcomes at 10 years after randomization for eyes undergoing cryotherapy vs eyes serving as controls, for patients enrolled in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP). METHODS The randomized cohort originally consisted of 291 preterm children with birth weights less than 1251 g who developed a defined threshold of ROP severity in one or both eyes. Patients with bilateral threshold ROP (n = 240) were randomly assigned to receive cryotherapy to one eye and no cryotherapy to the other eye. Those with ROP of less severity than threshold in the fellow eye ("asymmetric"; n = 51) were randomly assigned to cryotherapy or no cryotherapy in the eye with threshold ROP. Ten years later, a tester who was masked to treatment status of each eye measured distance and near visual acuity, with "unfavorable" outcome being 20/200 or worse. Patients also were evaluated by study-certified ophthalmologists who assessed ROP residua primarily in the posterior pole of the fundus, with unfavorable outcome being a posterior retinal fold or worse. RESULTS For the 247 children examined, both functional and structural primary outcomes showed fewer unfavorable outcomes in treated vs control eyes: 44.4% vs 62.1% (P<.001) for distance visual acuity and 27.2% vs 47.9% (P<.001) for fundus status. Near acuity results were similar to those for distance (42.5% vs 61.6%; P<.001). Total retinal detachments had continued to occur in control eyes, increasing from 38.6% at 5(1/2) years to 41.4% at 10 years, while treated eyes remained stable (at 22.0%). A previously disturbing subgroup trend that more control eyes than treated eyes had visual acuity of 20/40 or better (in the 5(1/2)-year report) was no longer present at 10 years; eyes that received cryotherapy were found at least as likely as control eyes to have 20/40 or better visual acuity. CONCLUSIONS At 10 years, eyes that had received cryotherapy were much less likely than control eyes to be blind. A previous trend for a higher proportion of sighted control eyes than sighted treated eyes to show acuity in the normal range was not confirmed. The results show long-term value from cryotherapy in preserving visual acuity in eyes with threshold ROP.

Background: The LIGHT-ROP Study was a multicenter, prospective, randomized, controlled, clinical trial designed to determine if a reduction in ambient light exposure to premature infants' eyes would reduce the incidence of retinopathy of prematurity (ROP). Previous clinical reports were contradictory and had one or more methodological flaws.Methods: The LIGHT-ROP trial was designed in rigorous fashion to include randomization to treatment or control groups, masking of examiners, an adequate sample size of high-risk infants, a universal ROP classification system, a reliable and reproducible ophthalmologic examination protocol, a controlled method of light reduction, and monitoring of light levels in the nursery. The multicenter trial was conducted at three centers in Buffalo, Dallas, and San Antonio, with a separate coordinating center in Houston. The trial also utilized a-separate data and safety monitoring committee.Conclusion: The design of the LIGHT-ROP study represents the most rigorous and largest clinical trial to date. It has demonstrated that light reduction does not reduce the incidence of confirmed ROP in high risk infants.

PURPOSE: To evaluate the relationship between microbiologic factors, effect of treatment, and visual outcome in the Endophthalmitis Vitrectomy Study.METHODS: Four hundred twenty patients were enrolled in the Endophthalmitis Vitrectomy Study between February 1990 and January 1994. Of these, 394 completed 9 to 12 months of follow-up. Patients presented with features of bacterial endophthalmitis within 6 weeks of cataract extraction or secondary intraocular lens implantation. The relations between visual outcome and the identity of infecting species, gram stain results, antibiotic susceptibilities, and presence of vitrectomy cassette growth were examined.RESULTS: Rates of achieving final visual acuity of 20/100 or better for the more common isolates were as follows: gram-positive, coagulase-negative micrococci, 84%; Staphylococcus aureus, 50%; streptococci, 30%; enterococci, 14%; and gram-negative organisms, 56%. A positive gram stain or infection with species other than gram-positive, coagulase-negative micrococci were significantly associated with poorer visual outcome (P <.001 for species group comparisons). However, presenting visual acuity was more powerful than microbiologic factors in predicting visual outcome and favorable response to vitrectomy. Bacterial growth from the vitrectomy cassette specimen had prognostic significance equivalent to growth from other intraocular sources.CONCLUSIONS: Visual prognosis was strongly associated with the type of infecting organism and gram stain positivity. However, visual acuity at initial presentation appeared to be more useful than microbiologic factors in predicting visual outcome and judging the value of immediate vitrectomy in acute bacterial endophthalmitis after cataract surgery.

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.

Objectives: To evaluate panretinal photocoagulation for ischemic central vein occlusion and macular grid-pattern photocoagulation for macular edema with reduced visual acuity due to central vein occlusion and to further define the natural history of central vein occlusion.Design: A multicenter randomized controlled clinical trial supported by the National Eye Institute, Bethesda, Md.Patients: A total of 728 eyes from 725 patients were entered into one or more of four study groups: perfused, nonperfused, indeterminate perfusion, and macular edema.Results: Follow-up of study patients is still in progress and no results are available for the randomized groups (nonperfused and macular edema). Thirty-eight (83%) of 46 evaluable eyes in the indeterminate group eventually demonstrated at least 10 disc areas of nonperfusion (28 eyes) or developed iris and/or angle neovascularization before retinal status could be determined (10 eyes). Four-month follow-up information is available for 522 of the 547 eyes in the perfused group. Thirty of these 522 eyes demonstrated iris and/or angle neovascularization at or before the 4-month follow-up visit. An additional 51 eyes had developed evidence of at least 10 disc areas of nonperfusion by the time of the 4-month visit.Conclusions: These findings confirm the importance of frequent follow-up examinations, including undilated slit-lamp examination of the iris, and gonioscopy in the management of all patients with recent onset of central vein occlusion.