Retina-Related Clinical Trials: A Resource Bibliography

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Chapter 94 Retina-Related Clinical Trials

A Resource Bibliography

Barbara S. Hawkins, Usha Chakravarthy

The subspecialty of Retina has probably seen some of the most innovative changes in the field of ophthalmology, largely owing to ground-breaking randomized clinical trials, with several or many centers typically participating, conducted to test novel treatment strategies in the management of diabetes, age-related macular degeneration, and retinal vaso-occlusive disease, among others. In previous decades, large clinical trials of interventions for retinal disorders laid the foundations for evidence-based clinical practice; foremost among these was the Diabetic Retinopathy Study, which was also one of the first initiatives of the National Eye Institute of the USA upon its creation as one of the National Institutes of Health. The Diabetic Retinopathy Study was one of the largest and best-conducted clinical trials of the safety and effectiveness of panretinal photocoagulation in diabetic retinopathy. This trial provided ophthalmologists with the evidence that was needed to show that proliferative diabetic retinopathy could be managed effectively with laser and also demonstrated the potential of the retinal community to generate the evidence base for treatment of retinal disorders through a networked approach. Since the Diabetic Retinopathy Study, the number of clinical trials in retinal disorders has burgeoned, with increasing sponsorship from industry and agencies in other countries. The purpose of this chapter is to provide the retinal specialist with a bibliography of publications in peer-reviewed journals from studies undertaken on the common retinal disorders of diabetes, age-related macular degeneration, and retinal vein occlusion, as well as other retinal disorders for which important clinical trials have been conducted. The organization of the citations is by retinal condition and then by specific randomized clinical trials or sets of trials, with clinical trials that focus on the same condition grouped together. The order of the conditions is chronologic by publication of findings from the first major clinical trial in each condition. Whenever a randomized trial was conducted as part of a larger study, preceded by a pilot study, or continued as an observational study, publications from the pilot study or selected publications from the larger study or observational study have been included in the bibliography for the clinical trial or set of clinical trials.

Diabetic retinopathy

Findings from several clinical trials of treatment or prevention of diabetic retinopathy are discussed in Chapters 47 (Nonproliferative diabetic retinopathy and diabetic macular edema) and 48 (Proliferative diabetic retinopathy).

Diabetic Retinopathy Study (DRS)

The historical importance of and other information about the DRS are described above. From 1972 through 1975, 1758 patients enrolled at DRS-participating centers.

Diabetic Retinopathy Study Research Group. Preliminary report on effects of photocoagulation therapy. Am J Ophthalmol 1976;81:383–96.

With 1732 patients enrolled and one eye of each patient assigned to photocoagulation, visual acuity of 5/200 or worse at two consecutive examinations 4 months apart was observed in 9% of untreated eyes versus 4% of treated eyes, leading to the decision to halt enrollment of new patients, to disseminate the findings to physicians, and to offer panretinal photocoagulation to all untreated eyes deemed to be at high risk of progression and vision loss.

Diabetic Retinopathy Study Research Group. Photocoagulation treatment of proliferative diabetic retinopathy: the second report of Diabetic Retinopathy Study findings. Ophthalmology 1978;85:82–106.

A detailed analysis of findings for all patients enrolled confirmed that scatter photocoagulation compared to no treatment reduced severe visual acuity loss and reduced the rate of progression to more severe stages of proliferative diabetic retinopathy. Throughout 3 years of follow-up, treated eyes had approximately half the risk of visual acuity of 5/200 or worse at two or more consecutive examinations.

Diabetic Retinopathy Study Research Group. Four risk factors for severe visual loss in diabetic retinopathy: the third report from the Diabetic Retinopathy Study. Arch Ophthalmol 1979;97:654–5.

The four risk factors were: (1) presence of vitreous or preretinal hemorrhage; (2) presence of new vessels; (3) location of new vessels on or near the optic disc; and (4) severity of new vessels. Risk of severe visual acuity loss increased by the number of factors present.

Diabetic Retinopathy Study Research Group. Photocoagulation treatment of proliferative diabetic retinopathy: a short report of long range results. Diabetic Retinopathy Study (DRS) report number 4. International Congress series no. 500, Diabetes 1979. In: Waldhausl WK, editor. Proceedings of the 10th Congress of the International Diabetes Federation. Amsterdam: Excerpta Medica; 1979. p. 789–94.

Diabetic Retinopathy Study Research Group. Photocoagulation treatment of proliferative diabetic retinopathy: relationship of adverse treatment effects to retinopathy severity. Diabetic Retinopathy Study report no. 5. Dev Ophthalmol 1981;2:248–61.

Diabetic Retinopathy Study Research Group. Diabetic Retinopathy Study report number 6: Design, methods, and baseline results. Invest Ophthalmol Vis Sci 1981;21:149–208.

Diabetic Retinopathy Study Research Group. Diabetic Retinopathy Study report number 7: A modification of the Airlie House classification of diabetic retinopathy. Invest Ophthalmol Vis Sci 1981;21:210–26.

Diabetic Retinopathy Study Research Group. Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of Diabetic Retinopathy Study (DRS) findings. DRS report number 8. Ophthalmology 1981;88:583–600.

Knatterud GL. Mortality experience in the Diabetic Retinopathy Study. Isr J Med Sci 1983;19:424–8.

Ederer F, Podgor MJ, the Diabetic Retinopathy Study Research Group. Assessing possible late treatment effects in stopping a clinical trial early: a case study. Diabetic Retinopathy Study report no. 9. Control Clin Trials 1984;5:373–81.

Rand LI, Prud’homme GJ, Ederer F, et al. Factors influencing the development of visual loss in advanced diabetic retinopathy: Diabetic Retinopathy Study (DRS) report no. 10. Invest Ophthalmol Vis Sci 1985;26:983–91.

Kaufman SC, Ferris FL, Swartz M, et al. Intraocular pressure following panretinal photocoagulation for diabetic retinopathy: Diabetic Retinopathy report no. 11. Arch Ophthalmol 1987;105:807–9.

Ferris FL, Podgor MJ, Davis MD, et al. Macular edema in Diabetic Retinopathy Study patients. Diabetic Retinopathy Study report number 12. Ophthalmology 1987;94:754–60.

Kaufman SC, Ferris FL, Seigel DG, et al. Factors associated with visual outcome after photocoagulation for diabetic retinopathy: Diabetic Retinopathy Study report no. 13. Invest Ophthalmol Vis Sci 1989;30:23–8.

Diabetic Retinopathy Study Research Group. Indications for photocoagulation treatment of diabetic retinopathy: Diabetic Retinopathy Study report no. 14. Int Ophthalmol Clin 1987;27:239–53.

UK Multicentre Controlled Study

This randomized trial of xenon arc photocoagulation for diabetic maculopathy was conducted concurrently with the DRS; initial findings were published shortly after the first publication from the DRS. This multicenter trial was sponsored by the British Diabetic Association and the Wellcome Trust.

Multicentre Controlled Study Coordinating Committee. Photocoagulation treatment of diabetic maculopathy. Interim report of a multicentre controlled study. Lancet 1975;2:1110–3.

Photocoagulation with the xenon arc led to less deterioration in visual acuity than no treatment. Initiation of treatment was recommended before visual acuity was “seriously impaired.”

Multicentre Controlled Study Coordinating Committee. Proliferative diabetic retinopathy: treatment with xenon-arc photocoagulation. Interim report of multicentre controlled randomised controlled trial. Br Med J 1977;1:739–41.

Photocoagulation with the xenon arc led to less monocular blindness than no treatment. New vessels on the disc regressed more in treated eyes than in untreated eyes.

Diabetic Retinopathy Vitrectomy Study (DRVS)

The primary goal of the DRVS was to compare early vitrectomy with conventional management of severe vitreous hemorrhage secondary to diabetic retinopathy. Patient accrual began in October 1976 and ended in June 1983. The DRVS was sponsored by the National Eye Institute.

Diabetic Retinopathy Vitrectomy Study Research Group. Two-year course of visual acuity in severe proliferative diabetic retinopathy with conventional management. Diabetic Retinopathy Vitrectomy Study (DRVS) report no. 1. Ophthalmology 1985;92:492–502.

After 2 years of follow-up, visual acuity of eyes assigned to conventional treatment was worse than 5/200 in 45% of eyes with more than four disc areas of new vessels and visual acuity of 10/30 to 10/50 at baseline.

Diabetic Retinopathy Vitrectomy Study Research Group. Early vitrectomy for severe vitreous hemorrhage in diabetic retinopathy. Two-year results of a randomized trial. Diabetic Retinopathy Vitrectomy Study report 2. Arch Ophthalmol 1985;103:1644–52.

Visual acuity was 10/20 or better in 25% of the early vitrectomy group compared with 15% of the deferral group 2 years after entry.

Diabetic Retinopathy Vitrectomy Study Research Group. Early vitrectomy for severe proliferative diabetic retinopathy in eyes with useful vision. Results of a randomized trial – Diabetic Retinopathy Vitrectomy Study report 3. Ophthalmology 1988;95:1307–20.

Diabetic Retinopathy Vitrectomy Study Research Group. Early vitrectomy for severe proliferative diabetic retinopathy in eyes with useful vision. Clinical application of results of a randomized trial – Diabetic Retinopathy Vitrectomy Study report 4. Ophthalmology 1988;95:1321–34.

Diabetic Retinopathy Vitrectomy Study Research Group. Early vitrectomy for severe vitreous hemorrhage in diabetic retinopathy. Four-year results of a randomized trial: Diabetic Retinopathy Vitrectomy Study report 5. Arch Ophthalmol 1990;108:958–64, 1452.

Early Treatment Diabetic Retinopathy Study (ETDRS)

The ETDRS was designed to evaluate the effectiveness of laser photocoagulation and aspirin, together and singly, in delaying or preventing progression of early diabetic retinopathy to more severe stages and blindness and to determine the optimum time to initiate photocoagulation in diabetic retinopathy. This multicenter clinical trial was sponsored by the National Eye Institute. Initiation of the ETDRS was a motivating factor in the development of a new visual acuity chart for use in prospective clinical research studies; see articles that report on the design and evaluation of the chart at the end of the ETDRS bibliography.

Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Arch Ophthalmol 1985;103:1796–806.

Eyes with clinically significant macular edema benefited from focal photocoagulation and were about half as likely to lose three or more lines of vision as eyes assigned to deferral of photocoagulation.

Early Treatment Diabetic Retinopathy Study Research Group. Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 2. Ophthalmology 1987;94:761–74.

Early Treatment Diabetic Retinopathy Study Research Group. Techniques for scatter and local photocoagulation treatment of diabetic retinopathy: Early Treatment Diabetic Retinopathy Study report no. 3. Int Ophthalmol Clin 1987;27:254–64.

Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema: Early Treatment Diabetic Retinopathy Study report no. 4. Int Ophthalmol Clin 1987;27:265–72.

This report summarizes ETDRS reports number 1 and number 2.

Early Treatment Diabetic Retinopathy Study Research Group. Case reports to accompany Early Treatment Diabetic Retinopathy Study reports 3 and 4. Int Ophthalmol Clin 1987;27:273–334.

Kinyoun J, Barton F, Fisher M et al. Detection of diabetic macular edema: ophthalmoscopy versus photography – Early Treatment Diabetic Retinopathy Study report number 5. Ophthalmology 1989;96:746–51.

Prior MJ, Prout T, Miller D, et al. C-peptide and the classification of diabetes mellitus patients in the Early Treatment Diabetic Retinopathy Study: report number 6. Ann Epidemiol 1993;3:9–17.

Early Treatment Diabetic Retinopathy Study Research Group. Early Treatment Diabetic Retinopathy Study design and baseline patient characteristics. ETDRS report number 7. Ophthalmology 1991;98:741–56.

Early Treatment Diabetic Retinopathy Study Research Group. Effects of aspirin treatment on diabetic retinopathy: ETDRS report number 8. Ophthalmology 1991;98:757–65.

Aspirin (650 mg/day) had no clinically beneficial or harmful effects in patients with retinopathy.

Early Treatment Diabetic Retinopathy Study Research Group. Early photocoagulation for diabetic retinopathy: ETDRS report number 9. Ophthalmology 1991;98:766–85.

Initiation of scatter photocoagulation was recommended for eyes with high-risk proliferative retinopathy. Whenever possible, scatter photocoagulation should be applied after completion of focal laser in eyes with macular edema.

Early Treatment Diabetic Retinopathy Study Research Group. Grading diabetic retinopathy from stereoscopic color fundus photographs – an extension of the modified Airlie House classification. ETDRS report number 10. Ophthalmology 1991;98:786–806.

Early Treatment Diabetic Retinopathy Study Research Group. Classification of diabetic retinopathy from fluorescein angiograms. ETDRS report number 11. Ophthalmology 1991;98:807–22.

Early Treatment Diabetic Retinopathy Study Research Group. Fundus photographic risk factors for progression of diabetic retinopathy: ETDRS report number 12. Ophthalmology 1991;98:823–33.

Severity of intraretinal microvascular abnormalities, hemorrhages and/or microaneurysms, and venous beading were the most important factors in predicting progression to proliferative diabetic retinopathy.

Early Treatment Diabetic Retinopathy Study Research Group. Fluorescein angiographic risk factors for progression of diabetic retinopathy: ETDRS report number 13. Ophthalmology 1991;98:834–40.

Fluorescein leakage, capillary loss and dilation, and various arteriolar abnormalities were associated with progression to proliferative retinopathy.

Early Treatment Diabetic Retinopathy Study Investigators. Aspirin effects on mortality and morbidity in patients with diabetes mellitus: Early Treatment Diabetic Retinopathy Study report 14. JAMA 1992;268:1292–300.

Fong DS, Barton FB, Bresnick GH, et al. Impaired color vision associated with diabetic retinopathy: Early Treatment Diabetic Retinopathy Study report no. 15. Am J Ophthalmol 1999;128:612–7.

Chew EY, Williams GA, Burton TC, et al. Aspirin effects on the development of cataracts in patients with diabetes mellitus: Early Treatment Diabetic Retinopathy Study report 16. Arch Ophthalmol 1992;110:339–42.

Flynn HW, Chew EY, Simons BD, et al. Pars plana vitrectomy in the Early Treatment Diabetic Retinopathy Study. ETDRS report number 17. Ophthalmology 1992;99:1351–7.

Ferris FL. Early photocoagulation in patients with either type I or type II diabetes. Trans Am Ophthalmol Soc 1996;94:505–36.

Patients with type 2 diabetes were more likely to benefit from early scatter photocoagulation than patients with type 1 diabetes based on analysis of data from both the DRS and ETDRS.

Davis MD, Fisher MR, Gangnon RE, et al. Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss: Early Treatment Diabetic Retinopathy Study report no. 18. Invest Ophthalmol Vis Sci 1998;39:233–52.

Early Treatment Diabetic Retinopathy Study Research Group. Focal photocoagulation treatment of diabetic macular edema. Relationship of treatment effect to fluorescein angiographic and other retinal characteristics at baseline: ETDRS report no. 19. Arch Ophthalmol 1995;113:1144–55.

Chew EY, Klein ML, Murphy RP, et al. Effects of aspirin on vitreous/preretinal hemorrhage in patients with diabetes mellitus: Early Treatment Diabetic Retinopathy Study report no. 20. Arch Ophthalmol 1995;113:52–5.

Braun CI, Benson WE, Remaley NA, et al. Accommodative amplitudes in the Early Treatment Diabetic Retinopathy Study. ETDRS report number 21. Retina 1995;15:275–81.

Chew EY, Klein ML, Ferris FL, et al. Association of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy: Early Treatment Diabetic Retinopathy Study (ETDRS) report 22. Arch Ophthalmol 1996;114:1079–84.

Fong DS, Segal PP, Myers F, et al. Subretinal fibrosis in diabetic macular edema. ETDRS report 23. Arch Ophthalmol 1997;115:873–7.

Fong DS, Ferris FL, Davis MD, et al. Causes of severe visual loss in the Early Treatment Diabetic Retinopathy Study: ETDRS report no. 24. Am J Ophthalmol 1999;127:137–41.

Chew EY, Benson WE, Remaley NA, et al. Results after lens extraction in patients with diabetic retinopathy: Early Treatment Diabetic Retinopathy Study report number 25. Arch Ophthalmol 1999;117:1600–6.

Cusick M, Chew EY, Hoogwert B, et al. and the ETDRS Research Group. Risk factors for renal replacement therapy in the Early Treatment Diabetic Retinopathy Study (ETDRS). ETDRS report no. 26. Kidney International 2004;66:1173–9.

Cusick M, Davis MD, Meleth AD, et al for the Early Treatment Diabetic Retinopathy Study (ETDRS) Research Group. Associations of mortality and diabetes complications in patients with type 1 and type 2 diabetes. Early Treatment Diabetic Retinopathy Study report no. 27. Diabetes Care 2005;28:617–25.

Barton FB, Fong DS, Knatterud GL, et al. Classification of Farnsworth–Munsell 100-hue test results in the Early Treatment Diabetic Retinopathy Study. Am J Ophthalmol 2004;138:119–24.

Gangnon RE, Davis MD, Hubbard LD, et al. A severity scale for diabetic macular edema developed from ETDRS data. Invest Ophthalmol Vis Sci 2008;49:5041–7.

Ferris FL, Kassoff A, Bresnick GH, et al. New visual acuity charts for clinical research. Am J Ophthalmol 1982;94:91–6.

Ferris FL, Sperduto RD. Standardized illumination for visual acuity testing in clinical research. Am J Ophthalmol 1982;94:97–8.

Ferris FL, Freidlin V, Kassoff A, et al. Relative letter and position difficulty on visual acuity charts from the Early Treatment Diabetic Retinopathy Study. Am J Ophthalmol 1993;116:735–40.

Sorbinil Retinopathy Trial (SRT)

The SRT was sponsored by the National Eye Institute and by Pfizer.

Sorbinil Retinopathy Trial Research Group. A randomized trial of sorbinil, an aldose reductase inhibitor, in diabetic retinopathy. Arch Ophthalmol 1990;108:1234–44.

Sorbinil, as administered in the SRT, did not have a clinically important effect on the course of diabetic retinopathy in adults with insulin-dependent diabetes.

Sorbinil Retinopathy Trial Research Group. The Sorbinil Retinopathy Trial: neuropathy results. Neurology 1993;43:1141–9.

Cohen RA, Hennekens CH, Christen WG, et al. Determinants of retinopathy progression in type 1 diabetes mellitus. Am J Med 1999;107:45–51.

Christen WG, Manson JE, Bubes V, et al. Risk factors for progression of distal symmetric polyneuropathy in type 1 diabetes mellitus. Am J Epidemiol 1999;150:1142–51.

Krypton Argon Regression of Neovascularization Study (KARNS)

The KARNS was a multicenter clinical trial with the primary goal of comparing krypton red laser with argon blue–green laser for panretinal photocoagulation with respect to regression of disc neovascularization in diabetic retinopathy.

Singerman LJ, Ferris FL, Mowery RP, et al. Krypton laser for proliferative diabetic retinopathy: the Krypton Argon Regression of Neovascularization Study. J Diab Complications 1988;2:189–96.

Krypton Argon Regression of Neovascularization Study Research Group. Randomized comparison of krypton versus argon scatter photocoagulation for diabetic disc neovascularization. Ophthalmology 1993;100:1655–64.

Scatter photocoagulation with either krypton red or argon blue–green laser was equally effective in the treatment of proliferative diabetic retinopathy.

Diabetes Control and Complications Trial (DCCT)

The DCCT was a multicenter randomized clinical trial designed to compare intensive with conventional glucose control with respect to development and progression of early vascular and neurologic complications of insulin-dependent diabetes mellitus. The DCCT was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, the National Eye Institute, and the National Center for Research Resources (National Institutes of Health, US Department of Health and Human Services) and various corporate sponsors. A follow-up study of members of the DCCT cohort, the Epidemiology of Diabetes Interventions and Complications (EDIC), was undertaken to assess the long-term effects of intensive and conventional diabetes therapy during the DCCT.

Diabetes Control and Complications Trial Research Group. The Diabetes Control and Complications Trial (DCCT): design and methodologic considerations for the feasibility phase. Diabetes 1986;35:530–45.

Diabetes Control and Complications Trial Research Group. The Diabetes Control and Complications Trial (DCCT): Results of feasibility study. Diabetes Care 1987;10:1–10.

Diabetes Control and Complications Trial Research Group. Feasibility of centralized measurements of glycated hemoglobin in the Diabetes Control and Complications Trial, a multicenter study. Clin Chem 1987;33:2267–71.

Diabetes Control and Complications Trial Research Group. Implementation of a multicomponent process to obtain informed consent in the Diabetes Control and Complications Trial. Control Clin Trials 1989;10:83–96.

Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977–86.

Relative to rates in the conventional treatment arm, intensive therapy reduced onset and progression of diabetic retinopathy by 76% and 54%, respectively, occurrence of nephropathy by 54%, and onset of neuropathy by 60%.

Diabetes Control and Complications Trial Research Group. Expanded role of the dietician in the Diabetes Control and Complications Trial: implications for clinical practice. J Am Diet Assoc 1993;93:758–64, 767.

Diabetes Control and Complications Trial Research Group. Nutrition interventions for intensive therapy in the Diabetes Control and Complications Trial. J Am Diet Assoc 1993;93:768–72.

Diabetes Control and Complications Trial Research Group. Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus: Diabetes Control and Complications Trial. J Pediatr 1994;125:177–88.

In the DCCT cohort of young patients (13–17 years old), intensive control reduced the risk of development and progression of retinopathy compared to conventional treatment by 53% and 70%, respectively.

Diabetes Control and Complications Trial Research Group. A screening algorithm to identify clinically significant changes in neuropsychological functions in the Diabetes Control and Complications Trial. J Clin Exp Neuropsychol 1994;16:303–16.

Diabetes Control and Complications Trial Research Group. The effect of intensive diabetes treatment on the progression of diabetic retinopathy in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial. Arch Ophthalmol 1995;113:36–51.

Intensive therapy significantly reduced the risk of a three-step progression of retinopathy to 12% compared to 54% in the conventional therapy group.

Diabetes Control and Complications Trial Research Group. Progression of retinopathy with intensive versus conventional treatment in the Diabetes Control and Complications Trial. Ophthalmology 1995;102:647–61.

Intensive therapy reduced the risk of development of any retinopathy to 70% from 90% in the conventional treatment arm and also reduced the risk of progression. Intensive therapy was most effective when initiated early after diagnosis of insulin-dependent diabetes mellitus.

Diabetes Control and Complications Trial Research Group. Implementation of treatment protocols in the Diabetes Control and Complications Trial. Diabetes Care 1995;18:361–76.

Diabetes Control and Complications Trial (DCCT) Research Group. Effect of intensive diabetes management on macrovascular events and risk factors in the Diabetes Control and Complications Trial. Am J Cardiol 1995;75:894–903.

Diabetes Control and Complications Trial Research Group. The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the Diabetes Control and Complications Trial. Diabetes 1995;44:968–83.

Diabetes Control and Complications Trial (DCCT) Research Group. Effect of intensive diabetes treatment on nerve conduction in the Diabetes Control and Complications Trial. Ann Neurol 1995;38:869–80.

Diabetes Control and Complications Trial Research Group. Influence of intensive diabetes treatment on quality-of-life outcomes in the Diabetes Control and Complications Trial. Diabetes Care 1996;19:195–203.

Diabetes Control and Complications Trial Research Group. The absence of a glycemic threshold for the development of long-term complications: the perspective of the Diabetes Control and Complications Trial. Diabetes 1996;45:1289–98.

Diabetes Control and Complications Trial Research Group. Lifetime benefits and costs of intensive therapy as practiced in the Diabetes Control and Complications Trial. JAMA 1996;276:1400–15.

Diabetes Control and Complications Trial Research Group. Pregnancy outcomes in the Diabetes Control and Complications Trial. Am J Obstet Gynecol 1996;174:1343–53.

Diabetes Control and Complications Trial Research Group. Effect of intensive therapy on residual β-cell function in patients with type I diabetes in the Diabetes Control and Complications Trial. Ann Intern Med 1998;128:517–23.

Diabetes Control and Complications Trial Research Group. Early worsening of diabetic retinopathy in the Diabetes Control and Complications Trial. Arch Ophthalmol 1998;116:874–86.

Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group. Design, implementation, and preliminary results of a long-term follow-up of the Diabetes Control and Complications Trial cohort. Diabetes Care 1999;22:99–111.

Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group. Effect of intensive diabetes treatment on carotid artery wall thickness in the Epidemiology of Diabetes Interventions and Complications. Diabetes 1999;48:383–90.

Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Retinopathy and nephropathy in patients with type I diabetes four years after a trial of intensive therapy. N Engl J Med 2000;342:381–9.

The intensive therapy group continued to demonstrate a persistent reduction in the risk of progressive retinopathy and nephropathy compared to the conventional therapy group 4 years after the conclusion of the DCCT.

Diabetes Control and Complications Trial Research Group. Effect of pregnancy on microvascular complications in the Diabetes Control and Complications Trial. Diabetes Care 2000;23:1084–91.

Diabetes Control and Complications Trial (DCCT)/ Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group. Beneficial effects of intensive therapy of diabetes during adolescence: outcomes after the conclusion of the Diabetes Control and Complications Trial (DCCT). J Pediatr 2001;139:804–12.

Diabetes Control and Complications Trial Research Group. Influence of intensive diabetes treatment on body weight and composition of adults with type 1 diabetes in the Diabetes Control and Complications Trial. Diabetes Care 2001;24:1711–21.

Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA 2002;287:2563–9.

Diabetes Control and Complications Trials/Epidemiology of Diabetes Interventions and Complications Research Group. Intensive diabetes therapy and carotid intima-media thickness in type 1 diabetes mellitus. N Engl J Med 2003;348:2294–303.

Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: the Epidemiology of Diabetes Interventions and Complications (EDIC) Study. JAMA 2003;290(16):2159–67.

Lyons TJ, Jenkins AJ, Zheng D, et al. Diabetic retinopathy and serum lipoprotein subclasses in the DCCT/EDIC cohort. Invest Ophthalmol Vis Sci 2004;45:910–8.

Nathan DM, Cleary PA, Backlund JY, et al. for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005;353(25):2643–53.

Steffes M, Cleary P, Goldstein D, et al. Hemoglobin A1c measurements over nearly two decades: sustaining comparable values throughout the Diabetes Control and Complications Trial and the Epidemiology of Diabetes Interventions and Complications Study. Clin Chem 2005;51(4):753–8.

Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Prolonged effect of intensive therapy on the risk of retinopathy complications in patients with type 1 diabetes mellitus. Arch Ophthalmol 2008;126(12):1707–15.

Hubbard LD, Sun W, Cleary PA, et al. for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study Research Group. Comparison of digital and film grading of diabetic retinopathy severity in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study. Arch Ophthalmol 2011;129(6):718–26.

UK Prospective Diabetes Study (UKPDS)

Since 1983, the UKPDS investigators have published more than 75 articles to report findings from this prospective study.

United Kingdom Prospective Diabetes Study Group. UK Prospective Study of Therapies of Maturity-Onset Diabetes. I: Effect of diet, sulphonylurea, insulin or biguanide therapy on fasting plasma glucose and body weight over 1 year. Diabetelogia 1983;24:404–11.

United Kingdom Prospective Study Group. United Kingdom Prospective Diabetes Study. III. Prevalence of hypertension and hypotensive therapy in patients with newly diagnosed diabetes. Hypertension 1985;7(Suppl 2):8–13.

United Kingdom Prospective Study Group. United Kingdom Prospective Diabetes Study. IV. Characteristics of newly-presenting type 2 diabetic patients: male preponderance and obesity at different ages. Diabetic Med 1988;5:154–9.

United Kingdom Prospective Diabetes Study Group. United Kingdom Prospective Diabetes Study. VI. Complications in newly diagnosed type 2 diabetic patients and their association with different clinical and biochemical risk factors. Diabetes Res 1990;13:1–11.

United Kingdom Prospective Diabetes Study Group. UK Prospective Diabetes Study (UKPDS): VIII. Study design, progress and performance. Diabetologia 1991;34:877–90.

United Kingdom Prospective Diabetes Study Group. UK Prospective Diabetes Study IX: Relationships of urinary albumin and N-acetylglucosaminidase to glycemia and hypertension at diagnosis of type 2 (non-insulin-dependent) diabetes mellitus and after 3 months diet therapy. Diabetologia 1992;36:835–42.

United Kingdom Prospective Diabetes Study Group. UK Prospective Diabetes Study (UKPDS) XII. Differences between Asian, Afro-Caribbean, and White Caucasian type 2 diabetic patients at diagnosis of diabetes. Diabetic Med 1994;11:670–7.

Kohner EM, Aldington SJ, Stratton IM, et al. United Kingdom Prospective Diabetes Study, 30: Diabetic retinopathy at diagnosis of non-insulin-dependent diabetes mellitus and associated risk factors. Arch Ophthalmol 1998;116:297–303.

United Kingdom Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837–53.

Over a 10-year period, a 25% risk reduction in microvascular endpoints was observed in the intensive treatment group (median hemoglobin (Hb) A1c 7.0%) compared with the conventional treatment group (median HbA1c 7.9%).

United Kingdom Prospective Diabetes Study (UKPDS) Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. Br Med J 1998;317:705–13.

Tight blood pressure control (mean, 144/82 mmHg) compared to lesser control (mean, 154/87 mmHg) reduced progression rates of diabetic retinopathy and deterioration of visual acuity.

United Kingdom Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. Br Med J 1998;317:713–20.

United Kingdom Prospective Diabetes Study Group. Cost effectiveness of improved blood glucose control in hypertensive patients with type 2 diabetes: UKPDS 40. Br Med J 1998;317:720–6.

Stratton IM, Kohner EM, Aldington SJ, et al. UKPDS 50: Risk factors for incidence and progression of retinopathy in type II diabetes over 6 years from diagnosis. Diabetologia 2001;44:156–63.

Of 1216 patients without retinopathy at diagnosis of type 2 diabetes, 22% had developed retinopathy (microaneurysms or worse in both eyes) by 6 years after diagnosis. HbA1c was strongly associated with incidence and, especially, progression of retinopathy. Incidence of retinopathy also was strongly associated with systolic blood pressure. Smoking was associated with a reduced incidence of retinopathy.

Gray A, Clarke P, Farmer A, et al. Implementing intensive control of blood glucose concentration and blood pressure in type 2 diabetes in England: cost analysis (UKPDS 63). Br Med J 2002;325:860–5.

UK Prospective Diabetes Study (UKPDS) Group. Risks of progression of retinopathy and vision loss related to tight blood pressure control in type 2 diabetes mellitus (UKPDS 69). Arch Ophthalmol 2004;122:1631–40.

Stratton IM, Cull CA, Adler AI, et al. Additive effects of glycaemia and blood pressure exposure on risk of complications in type 2 diabetes: a prospective observational study (UKPDS 75). Diabetologia 2006;49:1761–9.

Diabetic Retinopathy Clinical Research Network (DRCR.net)

The DRCR.net investigators have conducted a number of randomized clinical trials and observational studies of diabetic retinopathy. A complete list of publications from the DRCR.net is maintained on the DRCR.net Public Web Site (http://drcrnet.jaeb.org/Publications.aspx [cited 2012 27 Feb]).

Diabetic Retinopathy Clinical Research Network. Diurnal variation in retinal thickening measurement by optical coherence tomography in center-involved diabetic macular edema. Arch Ophthalmol 2006;124:1701–7.

Diabetic Retinopathy Clinical Research Network. Reproducibility of macular thickness and volume using Zeiss optical coherence tomography in patients with diabetic macular edema. Ophthalmology 2007;114:1520–5.

Diabetic Retinopathy Clinical Research Network. A phase 2 randomized clinical trial of intravitreal bevacizumab for diabetic macular edema. Ophthalmology 2007;114(10):1860–7.

Bhavsar AR, Ip MS, Glassman AR for the DRCRnet and the SCORE Study Group. The risk of enophthalmitis following intravitreal triamcinolone injection in the DRCRnet and SCORE clinical trials. Am J Ophthalmol 2007;144:454–6.

Writing Committee for the Diabetic Retinopathy Clinical Research Network. Comparison of the modified Early Treatment Diabetic Retinopathy Study and mild macular grid laser photocoagulation strategies for diabetic macular edema. Arch Ophthalmol 2007;124:469–80.

Bressler NM, Edwards AR, Antoszyk AN, et al. on behalf of the Diabetic Retinopathy Clinical Research Network. Retinal thickness on Stratus optical coherence tomography in people with diabetes and minimal or no diabetic retinopathy. Am J Ophthalmol 2008;145:894–901.

Diabetic Retinopathy Clinical Research Network. A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology 2008;115:1447–59.

Scott IU, Bressler NM, Bressler SB, et al. and the Diabetic Retinopathy Clinical Research Network. Agreement between clinician and reading center gradings of diabetic retinopathy severity level at baseline in a phase 2 study of intravitreal bevacizumab for diabetic macular edema. Retina 2008;28:38–40.

Browning DJ, Altaweel MM, Bressler NM, et al. on behalf of the Diabetic Retinopathy Clinical Research Network. Diabetic macular edema: What is focal and what is diffuse? Am J Ophthalmol 2008;146:649–55.

Diabetic Retinopathy Clinical Research Network. Three-year follow up of a randomized trial comparing focal/grid photocoagulation and intravitreal triamcinolone for diabetic macular edema. Arch Ophthalmol 2009;127(3):245–51.

Bressler NM, Edwards AR, Beck RW, et al. for the Diabetic Retinopathy Clinical Research Network. Exploratory analysis of diabetic retinopathy progression through 3 years in a randomized clinical trial that compares intravitreal triamcinolone acetonide with focal/grid photocoagulation. Arch Ophthalmol 2009;127(12):1566–71.

Diabetic Retinopathy Clinical Research Network. Observational study of the development of diabetic macular edema following panretinal (scatter) photocoagulation given in 1 or 4 sittings. Arch Ophthalmol 2009;127(2):132–40.

Sun JK, Aiello LP, Stockman M, et al. for the Diabetic Retinopathy Clinical Research Network. Effects of dilation on electronic-ETDRS visual acuity (EVA) in diabetic patients. Invest Ophthalmol Vis Sci 2009;50(4):1580–4.

Diabetic Retinopathy Clinical Research Network Writing Committee. Vitrectomy outcomes in eyes with diabetic macular edema and vitreomacular traction. Ophthalmology 2010;117:1087–93.

Diabetic Retinopathy Clinical Research Network Writing Committee: Googe J, Brucker AJ, Bressler NM, et al. Randomized trial evaluating short-term effects of intravitreal ranibizumab or triamcinolone acetonide on macular edema after focal/grid laser for diabetic macular edema in eyes also receiving panretinal photocoagulation. Retina 2011;31:1009–27.

Diabetic Retinopathy Clinical Research Network. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 2010;117:1064–77.

Diabetic Retinopathy Clinical Research Network. Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 2011;118:609–14.

Other diabetic retinopathy trials

Chaturvedi N, Sjolie A-K, Stephenson JM, et al. and the EUCLID Study Group. Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes. Lancet 1998;351:28–31.

Keech AC, Mitchell P, Summanen PA, et al. for the FIELD study investigators. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet 2007;370:1687–97.

Sjolie AK, Klein R, Porta M, et al. for the DIRECT Programme Study Group. Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomised placebo-controlled trial. Lancet 2008;372:1385–93.

Chaturvedi N, Porta M, Klein R, et al. for the DIRECT Programme Study Group. Effect of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials. Lancet 2008;372:1394–402.

Stolk RP, Vingerling JR, Cruickshank JK, et al. on behalf of the AdRem project team and ADVANCE management committee. Rationale and design of the AdRem study: Evaluating the effects of blood pressure lowering and intensive glucose control on vascular retinal disorders in patients with type 2 diabetes mellitus. Contemp Clin Trials 2007;28:6–17.

Stolk RP, Thom SAMcG, van Schooneveld MJ, et al. on behalf of the AdRem Project Team and ADVANCE Management Committee. Retinal vascular lesions in patients with Caucasian and Asian origin with type 2 diabetes. Baseline results from the ADVANCE Retinal Measurements (AdRem) study. Diabetes Care 2008;31:708–13.

Beulens JWJ, Patel A, Vingerling JR, et al. on behalf of the AdRem project team and ADVANCE management committee. Effects of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in patients with type 2 diabetes mellitus: a randomised controlled trial. Diabetologia 2009;52:2027–36.

Lee CC, Stolk RP, Adler AI, et al. on behalf of the AdRem project team and ADVANCE management committee. Association between alcohol consumption and diabetic retinopathy and visual acuity – the AdRem Study. Diabet Med 2010;27:1130–7.

Chew EY, Ambrosium WT, Howard LT, et al. for the ACCORD Study Group. Rationale, design, and methods of the Action to Control Cardiovascular Risk in Diabetes Eye Study (ACCORD-EYE). Am J Cardiol 2007;99(Suppl):103i-111i.

ACCORD Study Group and ACCORD Eye Study Group. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med 2010;363:233–44.

Ambrosius WT, Danis RP, Goff DC, et al. for the ACCORD Study Group. Lack of association between thiazolidinediones and macular edema in type 2 diabetes. Arch Ophthalmol 2010;128(3):312–8.

Ahmadieh H, Shoeibi N, Entezari M, et al. Intravitreal bevacizumab for prevention of early postvitrectomy hemorrhage in diabetic patients. A randomized clinical trial. Ophthalmology 2009;116:1943–8.

Gillies MC, Simpson JM, Gaston C, et al. Five-year results of a randomized trial with open-label extension of triamcinolone acetonide for refractory diabetic macular edema. Ophthalmology 2009;116:2182–7.

Nguyen QD, Shah SM, Heier JS, et al. for the READ-2 Study Group. Primary end point (six months) results of the Ranibizumab for Edema of the mAcula in Diabetes (READ-2) Study. Ophthalmology 2009;116:2175–81.

Nguyen QD, Shah SM, Khwaja AA, et al. for the READ-2 Study Group. Two-year outcomes of the Ranibizumab for Edema of the mAcula in Diabetes (READ-2) Study. Ophthalmology 2010;117:2146–51.

Haller JA, Kuppermann BD, Blumenkranz MS, et al. for the Dexamethasone DDS Phase II Study Group. Randomized controlled trial of an intravitreous dexamethasone drug delivery system in patients with diabetic macular edema. Arch Ophthalmol 2010;128(3):289–96.

Mitchell P, Bandello F, Schmidt-Erfurth U, et al. on behalf of the RESTORE study group. The RESTORE Study. Ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology 2011;118:615–25.

Vein occlusions

Cochrane Systematic Review

Braithwaite T, Nanji AA, Greenberg PB. Anti-vascular endothelial growth factor for macular edema secondary to central retinal vein occlusion. Cochrane Database of Systematic Review 2010, Issue 10, Art. No.: CD007325. DOI: 10.1002/14651858.CD007325.pub2.

Branch Vein Occlusion Study (BVOS)

The BVOS was a multicenter randomized clinical trial sponsored by the National Eye Instititue and designed to assess in eyes with retinal branch vein occlusion whether scatter photocoagulation with the argon laser could prevent development of neovascularization and peripheral scatter photocoagulation could prevent vitreous hemorrhage, and whether macular photocoagulation would improve visual acuity in eyes with macular edema and visual acuity of 20/40 or worse. BVOS findings are discussed in Chapter 53 Branch retinal vein occlusion.

Finkelstein D, Clarkson J, Diddie K, et al. Branch vein occlusion: retinal neovascularization outside the involved segment. Ophthalmology 1982;89:1357–61.

Branch Vein Occlusion Study Group. Argon laser photocoagulation for macular edema in branch vein occlusion. Am J Ophthalmol 1984;98:271–82.

Argon laser photocoagulation improved visual acuity in eyes with macular edema secondary to retinal branch vein occlusion, macular edema, and visual acuity of 20/40 or worse, with a gain of 2 or more lines of visual acuity in more laser-treated eyes than untreated eyes.

Branch Vein Occlusion Study Group. Argon laser scatter photocoagulation for prevention of neovascularization and vitreous hemorrhage in branch vein occlusion: a randomized clinical trial. Arch Ophthalmol 1986;104:34–41.

Peripheral scatter argon laser photocoagulation decreased the risk of vitreous hemorrhage compared to untreated eyes. In addition, scatter treatment before development of neovascularization was not beneficial; treatment after development of neovascularization was recommended.

Central Vein Occlusion Study (CVOS)

The CVOS included two randomized trials and two observational studies in its design. The goals of the CVOS were: (1) to determine whether photocoagulation therapy could prevent iris neovascularization in eyes with central vein occlusion and evidence of ischemic retina; (2) to assess whether grid photocoagulation could reduce loss of central visual acuity due to macular edema secondary to central vein occlusion; (3) to describe the course and prognosis for eyes with central vein occlusion. Patients were divided into four groups at entry: (1) perfused; (2) nonperfused; (3) indeterminate perfusion; or (4) macular edema. Findings from the CVOS are discussed in Chapter 54 (Central retinal vein occlusion).

Central Vein Occlusion Study Group. Central Vein Occlusion Study of photocoagulation therapy. Baseline findings. Online J Curr Clin Trials 1993,Oct 14; Doc. No. 95.

Central Vein Occlusion Study Group. Baseline and early natural history report. The Central Vein Occlusion Study. Arch Ophthalmol 1993;111:1087–95.

Clarkson JG. Central Vein Occlusion Study: Photographic protocol and early natural history. Trans Am Ophthalmol Soc 1994;92:203–13.

Central Vein Occlusion Study Group. Evaluation of grid pattern photocoagulation for macular edema in central vein occlusion. The Central Vein Occlusion Study Group M report. Ophthalmology 1995;102:1425–33.

Macular grid photocoagulation reduced macular edema but did not provide a better visual acuity outcome than no treatment.

Central Vein Occlusion Study Group. A randomized clinical trial of early panretinal photocoagulation for ischemic central vein occlusion. The Central Vein Occlusion Study Group N report. Ophthalmology 1995;102:1434–4.

Prophylactic panretinal photocoagulation decreased development of angle neovascularization or 2 or more clock-hours of iris neovascularization but did not prevent neovascularization. These findings suggest that photocoagulation should be administered at the time neovascularization is detected.

Central Vein Occlusion Study Group. Natural history and clinical management of central retinal vein occlusion. Arch Ophthalmol 1997;115:486–91.

Standard Care vs COrticosteroid for REtinal Vein Occlusion Study (SCORE)

SCORE is a multicenter study sponsored by the National Eye Institute that includes two randomized trials of intravitreal triamcinolone, one for patients with central vein occlusion and one for patients with branch vein occlusion.

Scott IU, Vanveldhuisen PC, Oden N, et al., SCORE Study Investigator Group. SCORE Study report 1: Baseline associations between cenral retinal thickness and visual acuity in patients with retinal vein occlusion. Ophthalmology 2009;116(3):504–12.

Scott IU, Blodi BA, Ip MS, et al., SCORE Study Investigator Group. SCORE Study report 2: Interobserver agreement between investigator and reading center classification of retinal vein occlusion type. Ophthalmology 2009;116(4):756–61.

Ip MS, Oden NL, Scott IU, et al., SCORE Study Investigator Group. SCORE Study report 3: Study design and baseline characteristics. Ophthalmology 2009;116(9):1770–7.

Domalpally A, Blodi BA, Scott IU, et al., SCORE Study Investigator Group. The Standard Care vs. Corticosteroid for Retinal Vein Occlusion (SCORE) Study system for evaluation of optical coherence tomograms: SCORE Study report no. 4. Arch Ophthalmol 2009;127(11):1461–7.

Ip MS, Scott IU, VanVeldhuisen PC, et al., SCORE Study Research Group. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with observation to treat vision loss associated with macular edema secondary to central vein occlusion: Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) Study report no.5. Arch Ophthalmol 2009;127(6):1101–4.

Scott IU, Ip MS, VanVeldhuisen PC, et al., SCORE Study Research Group. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with standard care to treat vision loss associated with macular edema secondary to branch retinal vein occlusion: Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) Study report no. 6. Arch Ophthalmol 2009;127(9):1115–28.

Scott IU, Oden NL, VanVeldhuissen PC, et al., SCORE Study Investigator Group. SCORE Study report 7: Incidence of intravitreal silicone oil droplets associated with staked-on vs luer cone syringe design. Am J Ophthalmol 2009;148(5):725–32.

Oden N, VanVeldhuisen PC, Scott IU, Ip MS, SCORE Study Investigator Group. SCORE Study report 8: Closed tests for all pairwise comparisons of means. Drug Inform J 2010;44:405–20.

Blodi BA, Domalpally AM, Scott IU, et al. for the SCORE Study Research Group. Standard care vs. corticosteroid for retinal vein occlusion (SCORE) Study system for evaluation of stereoscopic color fundus photographs and fluorescein angiograms. SCORE Study Report 9. Arch Ophthalmol 2010;128(9):1140–5.

Scott IU, VanVeldhuisen PC, Oden NL, for the Standard Care versus COrticosteroid for REtinal Vein Occlusion Study Investigator Group. Baseline predictors of visual acuity and retinal thickness outcomes in patients with retinal vein occlusion: Standard Care versus Corticosteroid for Retinal Vein Occlusion Study report 10. Ophthalmology 2011;118:345–52.

Chan CK, Ip MS, VanVeldhuisen PC, et al. for the SCORE Study Investigator Group. SCORE Study report no. 11. Incidences of neovascular events in eyes with retinal vein occlusion. Ophthalmology 2011;118:1364–72.

Other clinical trials for vein occlusion

Campochiaro PA, Heier JS, Feiner L, et al. for the BRAVO Investigators. Ranibizumab for macular edema following branch retinal vein occlusion. Six-month primary end point results of a phase III study. Ophthalmology 2010;117:1102–12.

Brown DM, Campochiaro PA, Bhisitkul RB, et al. Sustained benefit from ranibizumab for macular edema following branch retinal vein occlusions: 12-month outcomes of a phase III study. Ophthalmology 2011;118:1594–602.

Brown DM, Campochiaro PA, Singh RP, et al for the CRUISE Investigators. Ranibizumab for macular edema following central retinal vein occulusion. Six-month primary end point results of a phase III study. Ophthalmology 2010;117:1124–39.

Age-related macular degeneration and other conditions associated with choroidal neovascularization

Findings from many of the trials listed below are discussed in Chapters 66 (Neovascular (Exudative or “Wet”) Age-Related Macular Degeneration), 67 (Pharmacotherapy of Age-Related Macular Degeneration), 68 (Myopic macular degeneration) 70 (Ocular Histoplasmosis). Because of the numerous trials that have been conducted for these conditions during the past three decades, the clinical trials cited have been subdivided into treatment trials and prevention trials.

Treatment trials

Macular Photocoagulation Study (MPS)

The MPS was initiated in 1979 under the sponsorship of the National Eye Institute to evaluate laser photocoagulation for choroidal neovascularization secondary to age-related macular degeneration and ocular histoplasmosis. In addition, small trials of laser photocoagulation for idiopathic choroidal neovascularization were conducted. The MPS Group conducted three multicenter randomized trials of argon laser photocoagulation of extrafoveal choroidal neovascularization (begun in 1979), three trials of krypton laser photocoagulation for juxtafoveal neovascular lesions (begun in 1981), and two trials of laser photocoagulation (with a second randomization of eyes assigned to laser photocoagulation between argon green and krypton red laser) of subfoveal choroidal neovascularization secondary to age-related macular degeneration only (begun in 1985).

Macular Photocoagulation Study Group. Argon laser photocoagulation for senile macular degeneration: results of a randomized clinical trial. Arch Ophthalmol 1982;100:912–8.

After fewer than half the eyes in each treatment arm had been followed for 1 year, severe loss of visual acuity from the baseline levels (loss of six or more lines on a logMar chart) was observed among 25% of laser-treated eyes versus 60% of untreated eyes, the first indication that any treatment for choroidal neovascularization was able to delay or prevent loss of visual acuity.

Macular Photocoagulation Study Group. Argon laser photocoagulation for ocular histoplasmosis: results of a randomized clinical trial. Arch Ophthalmol 1983;101:1347–57.

Laser photocoagulation of extrafoveal choroidal neovascularization was even more effective in eyes with ocular histoplasmosis than in eyes with age-related macular degeneration. By 2 years after enrollment, only 13% of laser-treated eyes versus 46% of untreated eyes had visual acuity 6 or more lines worse than at baseline.

Macular Photocoagulation Study Group. Argon laser photocoagulation for idiopathic neovascularization: results of a randomized clinical trial. Arch Ophthalmol 1983;101:1358–61.

Among a much smaller number of eyes with idiopathic extrafoveal choroidal neovascularization, the findings with respect to severe loss of visual acuity were intermediate between those of the other two MPS trials for extrafoveal lesions.

Macular Photocoagulation Study Group. Changing the protocol: a case report from the Macular Photocoagulation Study. Control Clin Trials 1984;5:203–16.

Macular Photocoagulation Study Group. Recurrent choroidal neovascularization after argon laser photocoagulation for neovascular maculopathy. Arch Ophthalmol 1986;104:503–12.

After more than 80% of the 284 eyes that initially had extrafoveal choroidal neovascularization had been followed for 3 years or more, 59% of eyes with age-related macular degeneration, 30% of eyes with ocular histoplasmosis, and 33% of eyes with idiopathic choroidal neovascularization had recurrent choroidal neovascularization documented at one or more follow-up examinations.

Macular Photocoagulation Study Group. Argon laser photocoagulation for neovascular maculopathy: three-year results from randomized clinical trials. Arch Ophthalmol 1986;104:694–701.

Initial reports of the effectiveness of laser photocoagulation were confirmed with follow-up for 3 years or longer of patients in all three trials for eyes with extrafoveal choroidal neovascularization.

Macular Photocoagulation Study Group. Krypton laser photocoagulation for neovascular lesions of ocular histoplasmosis: results of a randomized clinical trial. Arch Ophthalmol 1987;105:1499–1507.

The effect of laser photocoagulation of juxtafoveal choroidal neovascular lesions of ocular histoplasmosis was equally dramatic as when used to treat extrafoveal lesions: 6% versus 26% with severe visual acuity loss from baseline by the 3-year examination.

Macular Photocoagulation Study Group. Persistent and recurrent neovascularization after krypton laser photocoagulation for neovascular lesions of ocular histoplasmosis. Arch Ophthalmol 1989;107:344–52.

Blackhurst DW, Maguire MG, the Macular Photocoagulation Study Group. Reproducibility of refraction and visual acuity measurement under a standard protocol. Retina 1989;9:163–9.

Chamberlin JA, Bressler NM, Bressler SB, et al. The use of fundus photographs and fluorescein angiograms in the identification and treatment of choroidal neovascularization in the Macular Photocoagulation Study. Ophthalmology 1989;96:1526–34.

Macular Photocoagulation Study Group. Krypton laser photocoagulation for neovascular lesions of age-related macular degeneration: results of a clinical trial. Arch Ophthalmol 1990;108:816–24.

Three years after enrollment, 49% of laser-treated eyes versus 58% of untreated eyes that enrolled with juxtafoveal neovascular lesions had lost 6 or more lines of visual acuity from baseline. Laser treatment was recommended only for patients without definite hypertension.

Macular Photocoagulation Study Group. Persistent and recurrent neovascularization after krypton laser photocoagulation for neovascular lesions of age-related macular degeneration. Arch Ophthalmol 1990;108:825–31.

Macular Photocoagulation Study Group. Krypton laser photocoagulation for idiopathic neovascular lesions: results of a randomized clinical trial. Arch Ophthalmol 1990;108:832–7.

Bressler SB, Maguire MG, Bressler NM, et al. Relationship of drusen and abnormalities of the retinal pigment epithelium to the prognosis of neovascular macular degeneration. Arch Ophthalmol 1990;108:1442–7.

Large drusen and focal hyperpigmentation were risk factors for development of choroidal neovascularization in the fellow eye. Also, the risk of recurrent neovascularization was nearly three times higher among study eyes after laser treatment of extrafoveal choroidal neovascularization for patients who had large drusen in the fellow eye at baseline compared to those who did not.

Folk JC, Blackhurst DW, Alexander J, et al. Pretreatment fundus characteristics as predictors of recurrent choroidal neovascularization. Arch Ophthalmol 1991;109:1193–4.

Bressler NM, Bressler SB, Alexander J, et al. Loculated fluid: a previously undescribed fluorescein angiographic finding in choroidal neovascularization associated with macular degeneration. Arch Ophthalmol 1991;109:211–5.

Macular Photocoagulation Study Group. Argon laser photocoagulation for neovascular maculopathy: five-year results from randomized clinical trials. Arch Ophthalmol 1991;109:1109–14.

The benefits of laser photocoagulation of extrafoveal choroidal neovascularization due either to age-related macular degeneration or to ocular histoplasmosis and of idiopathic extrafoveal choroidal neovascularization persisted through 5 years of follow-up.

Macular Photocoagulation Study Group. Laser photocoagulation of subfoveal neovascular lesions in age-related macular degeneration: results of a randomized clinical trial. Arch Ophthalmol 1991;109:1220–31.

Despite initially larger losses of visual acuity from baseline among laser-treated than untreated eyes, by 2 years after entry, 21% of laser-treated eyes versus 38% of untreated eyes had visual acuity that was 6 or more lines worse than at baseline.

Macular Photocoagulation Study Group. Laser photocoagulation of subfoveal recurrent neovascular lesions in age-related macular degeneration: results of a randomized clinical trial. Arch Ophthalmol 1991;109:1232–41.

Laser photocoagulation was particularly effective for subfoveal recurrent choroidal neovascularization, with only 10% of laser-treated eyes versus 32% of untreated eyes having visual acuity six or more lines worse at the 2-year examination than at baseline.

Macular Photocoagulation Study Group. Subfoveal neovascular lesions in age-related macular degeneration: guidelines for evaluation and treatment in the Macular Photocoagulation Study. Arch Ophthalmol 1991;109:1242–57.

Fine SL, Wood WJ, Singerman LJ, et al. Laser treatment for subfoveal neovascular membranes in ocular histoplasmosis syndrome: results of a pilot randomized clinical trial. Arch Ophthalmol 1993;111:19–20.

Orr PR, Blackhurst DW, Hawkins BS. Patient and clinic factors predictive of missed visits and inactive status in a multicenter clinical trial. Control Clin Trials 1992;13:40–9.

Macular Photocoagulation Study Group. Five-year follow-up of fellow eyes of patients with age-related macular degeneration and unilateral extrafoveal choroidal neovascularization. Arch Ophthalmol 1993;111:1189–99.

Choroidal neovascularization developed in fellow eyes initially free of such lesions at a rate of approximately 5% per year during 5 years of follow-up.

Macular Photocoagulation Study Group. Laser photocoagulation of subfoveal neovascular lesions of age-related macular degeneration. Updated findings from two clinical trials. Arch Ophthalmol 1993;111:1200–9.

Macular Photocoagulation Study Group. Visual outcome after laser photocoagulation for subfoveal choroidal neovascularization secondary to age-related macular degeneration: the influence of initial lesion size and initial visual acuity. Arch Ophthalmol 1994;112:480–8.

Eyes with lesions larger than 2 disc areas and visual acuity of 20/160 or better had little or no benefit from treatment.

Macular Photocoagulation Study Group. Persistent and recurrent neovascularization after laser photocoagulation for subfoveal choroidal neovascularization of age-related macular degeneration. Arch Ophthalmol 1994;112:489–99.

Macular Photocoagulation Study Group. Laser photocoagulation for juxtafoveal choroidal neovascularization. Five-year results from randomized clinical trials. Arch Ophthalmol 1994;112:500–9.

Macular Photocoagulation Study (MPS) Group. Evaluation of argon green vs krypton red laser for photocoagulation of subfoveal choroidal neovascularization in the Macular Photocoagulation Study. Arch Ophthalmol 1994;112:1176–84.

Macular Photocoagulation Study Group. Laser photocoagulation for neovascular lesions nasal to the fovea. Results from clinical trials for lesions secondary to ocular histoplasmosis or idiopathic causes. Arch Ophthalmol 1995;113:56–61.

Macular Photocoagulation Study Group. The influence of treatment extent on the visual acuity of eyes treated with krypton laser for juxtafoveal choroidal neovascularization. Arch Ophthalmol 1995;113:190–4.

Macular Photocoagulation Study Group. Occult choroidal neovascularization. Influence on visual outcome in patients with age-related macular degeneration. Arch Ophthalmol 1995;114:400–12.

Macular Photocoagulation Study Group. Five-year follow-up of fellow eyes of individuals with ocular histoplasmosis and unilateral extrafoveal or juxtafoveal choroidal neovascularization. Arch Ophthalmol 1996;114:677–88.

Among fellow eyes free of choroidal neovascularization at the time patients enrolled in one of the MPS trials for eyes with ocular histoplasmosis, choroidal neovascularization developed in 9% within 5 years. New choroidal neovascular lesions developed in areas of the macula in which “atypical” histo spots were present earlier in follow-up.

Macular Photocoagulation Study Group. Risk factors for choroidal neovascularization in the second eye of patients with juxtafoveal or subfoveal choroidal neovascularization secondary to age-related macular degeneration. Arch Ophthalmol 1997;115:741–7.

Four independent risk factors were identified: (1) five or more drusen; (2) focal hyperpigmentation; (3) any large drusen; and (4) definite systemic hypertension. Five-year incidence of choroidal neovascularization in second eyes ranged from 7% in eyes with none of these risk factors to 87% of eyes with all four risk factors.

Jefferys JL, Alexander J, Hiner CJ, et al. for the Macular Photocoagulation Study Group. Reproducibility of gradings of retinal photographs of eyes with subfoveal choroidal neovascularization and age-related macular degeneration in the Macular Photocoagulation Study. Ophthalm Epidemiol 2008;15:191–201.

Other trials of laser treatment of choroidal neovascularization and a Cochrane systematic review

Coscas G, Soubrane G, Ramahefasolo C, et al. Perifoveal laser treatment for subfoveal choroidal new vessels in age-related macular degeneration. Results of a randomized clinical trial. Arch Ophthalmol 1991;109:1258–65.

Canadian Ophthalmology Study Group. Argon green vs krypton red laser photocoagulation of extrafoveal choroidal neovascular lesions. One-year results in age-related macular degeneration. Arch Ophthalmol 1993;111:181–5.

Canadian Ophthalmology Study Group. Argon green vs krypton red laser photocoagulation for extrafoveal choroidal neovascularization. One-year results in ocular histoplasmosis. Arch Ophthalmol 1994;112:1166–73.

Virgili G, Bini A. Laser photocoagulation for neovascular age-related macular degeneration. Cochrane Database of Systematic Reviews 2007, Issue 3, Art. No.: CD004763.DOI: 10.1002/14651858.CD004763.pub2.

Trials of photodynamic therapy with verteporfin (Visudyne) and a Cochrane systematic review

Multicenter randomized clinical trials of verteporfin were initiated in 1996 under industry sponsorship to evaluate safety and efficacy for treating subfoveal choroidal neovascularization secondary to age-related macular degeneration. The Verteporfin in Photodynamic Therapy (VIP) trial also investigated the use of verteporfin for subfoveal choroidal neovascularization secondary to pathologic myopia.

Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials – TAP report 1. Arch Ophthalmol 1999;117:1329–45.

After 1 year of follow-up, 67% of eyes with predominantly classic subfoveal lesions assigned to verteporfin compared with 39% of eyes assigned to placebo had lost fewer than 15 letters of visual acuity from baseline.

Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: two-year results of 2 randomized clinical trials – TAP report 2. Arch Ophthalmol 2001;119:198–207.

After 2 years of follow-up, 59% of eyes with predominantly classic subfoveal lesions assigned to verteporfin compared with 31% of eyes assigned to placebo had lost fewer than 15 letters of visual acuity from baseline.

Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Verteporfin therapy of subfoveal choroidal neovascularization in patients with age-related macular degeneration: additional information regarding baseline lesion composition’s impact on vision outcomes – TAP report no. 3. Arch Ophthalmol 2002;120:1443–54.

Rubin GS, Bressler NM, Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Effects of verteporfin therapy on contrast sensitivity: results from the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) investigation – TAP report no. 4. Retina 2002;22:536–44.

Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Verteporfin therapy for subfoveal choroidal neovascularization in age-related macular degeneration: three-year results of an open-label extension of 2 randomized clinical trials – TAP report no. 5. Arch Ophthalmol 2002;120:1307–14.

Bressler SB, Pieramici DJ, Koester JM, et al. Natural history of minimally classic subfoveal choroidal neovascular lesions in the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) investigation. Outcomes potentially relevant to management – TAP report no. 6. Arch Ophthalmol 2004;122:325–9.

Verteporfin in Photodynamic Therapy (VIP) Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in pathologic myopia with verteporfin. 1-year results of a randomized clinical trial – VIP report no. 1. Ophthalmology 2001;108:841–52.

After 1 year of follow-up, 72% of verteporfin-treated eyes compared with 44% of placebo-treated eyes lost fewer than eight letters, with 32% versus 15% improving at least five letters.

Verteporfin in Photodynamic Therapy Study Group. Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: two-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization – Verteporfin in Photodynamic Therapy report no. 2. Am J Ophthalmol 2001;131:541–60.

After 2 years of follow-up of patients with lesions composed of occult with no classic choroidal neovascularization who had recent disease progression, 55% of verteporfin-treated eyes compared with 68% of placebo-treated eyes lost at least 15 letters.

Verteporfin in Photodynamic Therapy (VIP) Study Group. Verteporfin therapy of subfoveal choroidal neovascularization in pathologic myopia: 2-year results of a randomized clinical trial – VIP report no. 3. Ophthalmology 2003;110:667–73.

After 2 years of follow-up, 36% of verteporfin-treated eyes compared with 51% of placebo-treated eyes lost at least eight letters on a logMAR visual acuity chart, with 40% versus 13% gaining at least five letters.

Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) and Verteporfin in Photodynamic Therapy (VIP) Study Groups. Effect of baseline lesion size, visual acuity, and lesion composition on visual acuity changes from baseline with and without verteporfin therapy in choroidal neovascularization secondary to age-related macular degeneration – TAP and VIP report no. 1. Am J Ophthalmol 2003;136:407–18.

Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) and Verteporfin in Photodynamic Therapy (VIP) Study Groups. Photodynamic therapy of subfoveal choroidal neovascularization with verteporfin. Fluorescein angiographic guidelines for evaluation and treatment – TAP and VIP report no. 2. Arch Ophthalmol 2003;121:1253–68.

Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) and Verteporfin in Photodynamic Therapy (VIP) Study Groups. Acute severe visual acuity decrease after photodynamic therapy with verteporfin: case reports from randomized clinical trials – TAP and VIP report no. 3. Am J Ophthalmol 2004;137:683–96.

Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) and Verteporfin in Photodynamic Therapy (VIP) Study Groups. Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: meta-analysis of 2-year safety results in three randomized clinical trials: TAP and VIP report no. 4. Retina 2004;24:1–12.

Japanese Age-Related Macular Degeneration Trial (JAT) Study Group. Japanese Age-Related Macular Degeneration Trial (JAT): 1-year results of photodynamic therapy with verteporfin in Japanese patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration. Am J Ophthalmol 2003;136:1049–61.

Wormald R, Evans JR, Smeeth LL, et al. Photodynamic therapy for neovascular age-related macular degeneration. Cochrane Database of Systematic Reviews 2007, Issue 3, Art. No.: CD002030. DOI: 10.1002/14651858.CD002030.pub3.

Submacular Surgery Trials (SST)

The SST was designed to evaluate the safety and effectiveness of surgical removal of subfoveal neovascularization. This set of multicenter randomized trials was sponsored by the National Eye Institute and was preceded by four randomized pilot trials, the SST Pilot Study.

Grossniklaus HE, Green WR, for the Submacular Surgery Trials Research Group. Histopathologic and ultrastructural findings of surgically excised choroidal neovascularization. Arch Ophthalmol 1998;116:745–9.

Submacular Surgery Trials Pilot Study Investigators. Submacular Surgery Trials randomized pilot trial of laser photocoagulation versus surgery for recurrent choroidal neovascularization secondary to age-related macular degeneration. I. Ophthalmic outcomes. Submacular Surgery Trials Pilot Study report number 1. Am J Ophthalmol 2000;130:387–407.

Of 31 patients in the laser treatment arm and 28 patients in the surgery arm with visual acuity measured 2 years after enrollment (89% of 70 patients enrolled in the SST Group R pilot trial), 65% of laser-treated eyes versus 50% of surgery eyes had visual acuity that was better than or no more than one line worse than at baseline.

Submacular Surgery Trials Pilot Study Investigators. Submacular Surgery Trials randomized pilot trial of laser photocoagulation versus surgery for recurrent choroidal neovascularization secondary to age-related macular degeneration. II. Quality of life outcomes. Submacular Surgery Trials Pilot Study report number 2. Am J Ophthalmol 2000;130:408–18.

SF-36 summary scores were similar for both treatment arms throughout 2 years of follow-up in the SST Group R pilot trial and were consistent with those of the general US population of similar age.

Submacular Surgery Trials Research Group. Responsiveness of the National Eye Institute Visual Function Questionnaire to changes in visual acuity: findings in patients with subfoveal choroidal neovascularization. SST report no. 1. Arch Ophthalmol 2003;121:531–9, Erratum 1513.

Submacular Surgery Trials Research Group. Clinical trial performance of community-based compared with university-based practices: lessons from the Submacular Surgery Trials. SST report no. 2. Arch Ophthalmol 2004;122:857–63.

Childs AL, the Submacular Surgery Trials Patient-Centered Outcomes Subcommittee for the Submacular Surgery Trials Pilot Study Investigators. Responsiveness of the SF-36 Health Survey to changes in visual acuity among patients with subfoveal choroidal neovascularization. Am J Ophthalmol 2004;137:373–5.

Sadda SR, Pieramici DJ, Marsh MJ, et al. Changes in lesion size after submacular surgery for subfoveal choroidal neovascularization in the Submacular Surgery Trials Pilot Study. Retina 2004;24:888–99.

Orr PR, Marsh MJ, Hawkins BS, et al. Evaluation of the Traveling Vision Examiner Program of the Submacular Surgery Trials Pilot Study. Ophthalmic Epidemiol 2005;12:47–57.

Submacular Surgery Trials Research Group. Effect of order of administration of health-related quality of life instruments on responses. SST report no. 3. Qual Life Res 2005;14:493–500.

Submacular Surgery Trials Research Group. Health- and vision-related quality of life among patients with choroidal neovascularization secondary to age-related macular degeneration at time of enrollment in randomized trials of submacular surgery. SST report no. 4. Am J Ophthalmol 2004;138:91–108.

Submacular Surgery Trials Research Group. Health- and vision-related quality of life among patients with ocular histoplasmosis or idiopathic choroidal neovascularization at time of enrollment in a randomized trial of submacular surgery. Submacular Surgery Trials report no. 5. Arch Ophthalmol 2005;123:78–88.

Submacular Surgery Trials Research Group. Patients’ perceptions of the value of current vision: assessment of preference values among patients with subfoveal choroidal neovascularization – the Submacular Surgery Trials (SST) Vision Preference Value Scale: SST report no. 6. Arch Ophthalmol 2004;122:1856–67.

Submacular Surgery Trials Research Group. Histopathological and ultrastructural features of surgically-excised subfoveal choroidal neovascular lesions: SST report no. 7. Arch Ophthalmol 2005;123:914–21.

Submacular Surgery Trials Research Group. Guidelines for interpreting retinal photographs and coding findings in the Submacular Surgery Trials (SST): SST report no. 8. Retina 2005;25:253–68.

Submacular Surgery Trials Research Group. Surgical removal versus observation for subfoveal choroidal neovascularization, either associated with the ocular histoplasmosis syndrome or idiopathic. I. Ophthalmic findings from a randomized clinical trial: Submacular Surgery Trials Group H Trial. SST report no. 9. Arch Ophthalmol 2004;122:1597–611.

After 2 years of follow-up, 55% of eyes in the surgery arm versus 46% of eyes in the observation arm had visual acuity that was better than or within one line (7 letters) of baseline visual acuity. Within the subgroup of eyes with visual acuity worse than 20/100 at baseline, these percentages were 76% and 50%, respectively, suggesting that surgery should be considered for such eyes.

Submacular Surgery Trials Research Group. Surgical removal versus observation for subfoveal choroidal neovascularization, either associated with the ocular histoplasmosis syndrome or idiopathic. II. Quality-of-life findings from a randomized clinical trial: SST Group H Trial. SST report no. 10. Arch Ophthalmol 2004;122:1616–28.

Submacular Surgery Trials Research Group. Surgery for subfoveal choroidal neovascularization in age-related macular degeneration: ophthalmic findings. SST report no. 11. Ophthalmology 2004;111:1967–80.

Findings from the SST Group N trial showed no clinically or statistically meaningful difference in ophthalmic outcomes between eyes assigned to surgery and eyes assigned to observation.

Submacular Surgery Trials Research Group. Surgery for subfoveal choroidal neovascularization in age-related macular degeneration: quality-of-life findings. SST report number 12. Ophthalmology 2004;111:1981–92.

Submacular Surgery Trials Research Group. Surgery for hemorrhagic choroidal neovascular lesions of age-related macular degeneration: ophthalmic findings. SST report no. 13. Ophthalmology 2004;111:1993–2006.

Surgery reduced the risk of severe visual acuity loss in the SST Group B trial but the percentage of eyes that achieved stable or improved visual acuity did not differ between the surgery and observation arms. In the absence of any other effective treatment, surgery may be considered in similar eyes with relatively good visual acuity to reduce the risk of severe visual acuity loss.

Submacular Surgery Trials Research Group. Surgery for hemorrhagic choroidal neovascular lesions of age-related macular degeneration: quality-of-life findings. SST report no. 14. Ophthalmology 2004;111:2007–14.

Submacular Surgery Trials Research Group. Comparison of 2D reconstructions of surgically excised subfoveal choroidal neovascularization with fluorescein angiographic features: SST report no. 15. Ophthalmology 2006;113:267–79.

Grossniklaus HE, Wilson DJ, Bressler SB, et al., for the Submacular Surgery Trials Research Group. Clinicopathologic studies of eyes that were obtained postmortem from four patients who were enrolled in the Submacular Surgery Trial: SST report no. 16. Am J Ophthalmol 2006;141:93–104.

Submacular Surgery Trials Research Group. Surgical removal vs observation for idiopathic or ocular histoplasmosis syndrome-associated subfoveal choroidal neovascularization. III. Vision Preference Value Scale findings from the randomized Group H Trial: SST report no. 17. Arch Ophthalmol 2008;126:1626–32.

Submacular Surgery Trials Research Group. Comparison of methods to identify incident cataract in eyes of patients with neovascular maculopathy. Submacular Surgery Trials report no. 18. Ophthalmology 2008;115:127–33.

Submacular Surgery Trials Research Group. Evaluation of minimum clinically meaningful changes in scores on the National Eye Institute Visual Function Questionnaire (NEI-VFQ). SST report no. 19. Ophthalmic Epidemiol 2007;14(4):205–15.

Submacular Surgery Trials Research Group. Incident choroidal neovascularization in fellow eyes of patients with unilateral subfoveal choroidal neovascularization secondary to age-related macular degeneration. SST report no. 20 from the Submacular Surgery Trials Research Group. Arch Ophthalmol 2007;125:1323–30.

Submacular Surgery Trials Research Group. Risk factors for second eye progression to advanced age-related macular degeneration. SST report no. 21. Retina 2009;29:1080–90.

Solomon SD, Dong LM, Haller JA, et al. on behalf of the SST Research Group and the SST Adverse Event Review Committee. Risk factors for rhegmatogenous retinal detachment in the Submacular Surgery Trials. SST report no. 22. Retina 2009;29:819–24.

Trials of radiotherapy for choroidal neovascularization and a Cochrane systematic review

Chakravarthy U, Houston RF, Archer D. Treatment of age-related subfoveal neovascular membranes by teletherapy: a pilot study. Br J Ophthalmol 1993;77:265–73.

Radiation Therapy for Age-Related Macular Degeneration (RAD) Study Group. A prospective, randomized, double-masked trial on radiation therapy for neovascular age-related macular degeneration (RAD Study). Ophthalmology 1999;106:2239–47.

Char DH, Irvine AI, Posner MD, et al. Randomized trial of radiation for age-related macular degeneration. Am J Ophthalmol 1999;127:574–8.

Kobayashi H, Kobayahsi K. Age-related macular degeneration: Long-term results of radiotherapy for subfoveal neovascular membranes. Am J Ophthalmol 2000;130:617–35.

Marcus DM, Sheils WC, Johnson MH, et al. External beam irradiation of subfoveal choroidal neovascularization complicating age-related macular degerneration. One-year results of a prospective, double-masked, randomized clinical trial. Arch Ophthalmol 2001;119:171–80.

Hart PM, Chakravarthy U, Mackenzie G, et al. Visual outcomes in the Subfoveal Radiotherapy Study: A randomized controlled trial of teletherapy for age-related macular degeneration. Arch Ophthalmol 2002;120:1029–38.

AMDRT Research Group. The Age-Related Macula Degeneration Radiotherapy Trial (AMDRT): One year results from a pilot study. Am J Ophthalmol 2004;138:818–28.

Jaakkola A, Heikkonen J, Tommila P, et al. Strontium plaque brachytherapy for exudative age-related macular degeneration. Three-year results of a randomized study. Ophthalmology 2005;112:567–73.

Zambarakji HJ, Lane AM, Ezra E, et al. Proton beam irradiation for neovascular age-related macular degeneration. Ophthalmology 2006;113:2012–9.

Evans JR, Sivagnanavel V, Chong V. Radiotherapy for neovascular age-related macular degeneration. Cochrane Database of Systematic Reviews 2010, Issue 5, Art. No.: CD004004. DOI: 10.1002/14651858.CD004004.pub3.

Trials of anti-VEGF therapy for choroidal neovascularization

Arguably the most important development in the treatment of neovascular age-related macular degeneration, antivascular endothelial growth factor (VEGF) agents have changed the treatment paradigm and the prognosis for this condition. Trials of anti-VEGF agents for neovascular age-related macular degeneration have been sponsored primarily by industry.

V.I.S.I.O.N.

Gragoudas ES, Adamis AP, Cunningham ET, et al. for the VEGF Inhibition Study in Ocular Neovascularization Clinical Trial Group. Pegaptanib for neovascular age-related macular degeneration. N Engl J Med 2004;351:2805–16.

VEGF Inhibition Study in Ocular Neovascularization (V.I.S.I.O.N.) Clinical Trial Group. Pegaptanib sodium for neovascular age-related macular degeneration. Two-year safety results of the two prospective, multicenter, controlled clinical trials. Ophthalmology 2006;113:992–1001.

MARINA

Rosenfeld PJ, Brown DM, Heier JS, et al. for the MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006;355:1419–31.

Monthly intravitreal injections of ranibizumab improved visual acuity by 15 or more letters from baseline in approximately one-third of treated eyes and yielded some improvement in almost all eyes so treated.

Kaiser PK, Blodi BA, Shapiro H, et al., for the MARINA Study Group. Angiographic and optical coherence tomographic results of the MARINA study of ranibizumab in neovascular age-related macular degeneration. Ophthalmology 2007;114:1868–75.

Boyer DS, Antoszyk AN, Auh CC, et al. for the MARINA Study Group. Subgroup analysis of the MARINA study of ranibizumab in neovascular age-related macular degeneration. Ophthalmology 2007;114:246–52.

Chang TS, Bressler NM, Fine JT, et al. for the MARINA Study Group. Improved vision-related function after ranibizumab treatment of neovascular age-related macular degeneration. Results of a randomized clinical trial. Arch Ophthalmol 2007;125(11):1460–9.

ANCHOR

Brown DM, Kaiser PK, Michels M, et al. for the ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 2006;355:1432–44.

Brown DM, Michels M, Kaiser PK, et al. for the ANCHOR Study Group. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degenerantion: Two-year results of the ANCHOR study. Ophthalmology 2009;116:57–65.

Bressler NM, Chang TS, Fine JT, et al. for the Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related Macular Degeneration (ANCHOR) Research Group. Improved vision-related function after ranibizumab vs photodynamic therapy. A randomized clinical trial. Arch Ophthalmol 2009;127(1):13–21.

FOCUS

Heier JS, Boyer DS, Ciulla TA, et al. for the FOCUS Study Group. Ranibizumab combined with verteporfin photodynamic therapy in neovascular age-related macular degeneration. Year 1 results of the FOCUS Study. Arch Ophthalmol 2006;124:1532–42.

Antoszyk AN, Tuomi L, Ghung CY, Singh A on behalf of the FOCUS Study Group. Ranibizumab combined with verteporfin photodynamic therapy in neovascular age-related macular degeneration (FOCUS): Year 2 results. Am J Ophthalmol 2008;145:862–74.

ABC Trial

Patel PJ, Chen FK, Rubin GS, et al. Intersession repeatability of visual acuity scores in age-related macular degeneration. Invest Ophthalmol Vis Sci 2008;49:4347–52.

Patel PJ, Chen FK, Rubin GS, et al. Intersession repeatability of contrast sensitivity scores in age-related macular degeneration. Invest Ophthalmol Vis Sci 2009;50:2621–5.

Tufail A, Patel PJ, Egan C, et al. Bevacizumab for neovascular age related macular degeneration (ABC Trial): multicentre randomised double masked study. Br Med J 2010;340:c2459. doi:10.1136/bmh.c2459.

Keane PA, Patel PJ, Ouyang Y, et al. Effects of retinal morphology on contrast sensitivity and reading ability in neovascular age-related macular degeneration. Invest Ophthalmol Vis Sci 2010;51:5431–7.

Patel PJ, Chen FK, Da Cruz L, et al. for the ABC Trial Study Group. Contrast sensitivity outcomes in the ABC Trial: A randomized trial of bevacizumab for neovascular age-related macular degeneration. Invest Ophthalmol Vis Sci 2011;52:3089–93.

Patel PJ, Chen FK, Da Cruz L, et al. Test–retest variability of reading performance metrics using MNREAD in patients with age-related macular degeneration. Invest Ophthalmol Vis Sci 2011;52:3854–9

PIER and other randomized trials of ranibizumab for neovascular age-related macular degeneration

Regillo CD, Brown DM, Abraham P, et al. on behalf of the PIER Study Group. Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER Study year 1. Am J Ophthalmol 2008;145:239–48.

Rosenfeld PJ, Rich RM, Lalwani GA. Ranibizumab: Phase III clinical trial results. Ophthalmol Clin N Am 2006;19:361–72.

Rosenfeld PJ, Shapiro H, Tuomi L, et al. for the MARINA and ANCHOR Study Groups. Characteristics of patients losing vision after 2 years of monthly dosing in the phase III ranibizumab clinical trials. Ophthalmology 2011;118:523–30.

Comparison of Age-related Macular Degeneration Treatments Trial (CATT)

CATT is sponsored by the National Eye Institute. Patient accrual was completed in December 2009.

Martin DF, Maguire MG, Fine SL. Identifying and eliminating the roadblocks to comparative effectiveness research. N Engl J Med 2010;363:105–7.

CATT Research Group. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med 2011;364:1897–908.

Treatment with ranibizumab and bevacizumab yielded similar visual acuity results when administered following the same regimen.

Comparisons of Age-Related Macular Degeneration Treatment Trials (CATT) Research Group. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration. Two-year results. Ophthalmology 2012;119:1388–98.

IVAN Study Investigators. Ranibizumab versus bevacizumab to treat neovascular age-related macular degeneration. One-year findings from the IVAN randomized trial. Ophthalmology 2012;119:1399–411.

Trials of other pharmacologic treatments for choroidal neovascularization

Pharmacological Therapy for Macular Degeneration Study Group. Interferon alfa-2 is ineffective for patients with choroidal neovascularization secondary to age-related macular degeneration. Results of a randomized placebo-controlled clinical trial. Arch Ophthalmol 1997;115:865–72.

Anecortave Acetate Clinical Study Group. Anecortave acetate as monotherapy for treatment of subfoveal neovascularization in age-related macular degeneration. Twelve-month clinical outcomes. Ophthalmology 2003;110:2372–85.

Slakter JS, Bochow T, D’Amico DJ, et al., Anecortave Acetate Clinical Study Group. Anecortave acetate (15 milligrams) versus photodynamic therapy for treatment of subfoveal neovascularization in age-related macular degeneration. Ophthalmology 2006;113:3–13.

Gillies MC, Simpson JM, Penfold P, et al. A randomized clinical trial of a single dose of intravitreal triamcinolone acetonide for neovascular age-related macular degeneration. One-year results. Arch Ophthalmol 2003;121:667–73.

Gillies MC, Simpson JM, Billson FA, et al. Safety of an intravitreal injection of triamcinolone. Results from a randomized clinical trial. Arch Ophthalmol 2004;122:336–40.

Neovascular Age-Related Macular Degeneration, Periocular Corticosteroids, and Photodynamic Therapy (NAPP) Trial Research Group. Periocular triamcinolone and photodynamic therapy for subfoveal choroidal neovascularization in age-related macular degeneration. Ophthalmology 2007;114;1713–21.

Prevention trials

Age-Related Eye Disease Study (AREDS and AREDS 2)

The goal of AREDS, a multicenter prospective study of persons aged 55–80 years, was to assess the clinical course of age-related macular degeneration and age-related cataract. AREDS included a placebo-controlled randomized prevention trial of high-dose vitamin and mineral supplements for patients at risk of age-related macular degeneration and of high-dose vitamin supplement for patients at risk of age-related cataract. Patient accrual began in September 1990 and ended in January 1998. The National Eye Institute sponsored AREDS and currently is sponsoring AREDS 2, a second study to evaluate other supplements.

Age-Related Eye Disease Study Research Group. The Age-Related Eye Disease Study (AREDS): design implications. AREDS report no. 1. Control Clin Trials 1999;20:573–600.

Age-Related Eye Disease Study Research Group. The Age-Related Eye Disease Study (AREDS): a clinical trial of zinc and antioxidants. AREDS report no. 2. J Nutr 2000;130(Suppl):1516–9.

Age-Related Eye Disease Study Research Group. Risk factors associated with age-related macular degeneration. A case-control study in the Age-Related Eye Disease Study: Age-Related Eye Disease Study report number 3. Ophthalmology 2000;107:2224–32.

Age-Related Eye Disease Study Research Group. The Age-Related Eye Disease Study (AREDS) system for classifying cataracts from photographs: AREDS report no. 4. Am J Ophthalmol 2001;131:167–75.

Age-Related Eye Disease Study Research Group. Risk factors associated with age-related nuclear and cortical cataract. A case-control study in the Age-Related Eye Disease Study, AREDS report no. 5. Ophthalmology 2001;108:1400–8.

Age-Related Eye Disease Study Research Group. The Age-Related Eye Diseases Study system for classifying age-related macular degeneration from stereoscopic color fundus photographs: the Age-Related Eye Disease Study report number 6. Am J Ophthalmol 2001;132:668–81.

Age-Related Eye Disease Study Research Group. The effect of five-year zinc supplementation on serum zinc, serum cholesterol, and hematocrit in persons assigned to treatment group in the Age-Related Eye Disease Study: AREDS report no. 7. J Nutr 2002;132:697–702.

Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss. AREDS report no. 8. Arch Ophthalmol 2001;119:1417–36.

With an average follow-up of the 3609 participants of 6.3 years, treatment with zinc alone or zinc in combination with antioxidants reduced the risk of advanced age-related macular degeneration among eyes at highest risk. Antioxidants plus zinc reduced the rate of moderate visual acuity loss.

Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E and beta carotene for age-related cataract and vision loss. AREDS report no. 9. Arch Ophthalmol 2001;119:1439–52.

Clemons TE, Chew EY, Bressler SB, et al. National Eye Institute Visual Function Questionnaire in the Age-Related Eye Disease Study (AREDS). AREDS report no. 10. Arch Ophthalmol 2003;121:211–7.

Age-Related Eye Disease Study Research Group. Potential public health impact of Age-Related Eye Disease Study results. AREDS report no. 11. Arch Ophthalmol 2003;121:1621–4.

Age-Related Eye Disease Study Research Group. Associations of mortality with ocular disorders and an intervention of high-dose antioxidants and zinc in the Age-Related Eye Disease Study. AREDS report no. 13. Arch Ophthalmol 2004;122:716–26.

Age-Related Eye Disease Study Research Group. Responsiveness of the National Eye Institute Visual Function Questionnaire to progression to advanced age-related macular degeneration, vision loss, and lens opacity. AREDS report no. 14. Arch Ophthalmol 2005;123:1207–14.

Rankin MW, Clemons TE, McBee WL, Age-Related Eye Disease Study (AREDS) Research Group. Correlation analysis of the in-clinic and telephone batteries from the AREDS cognitive function ancillary study. AREDS report no. 15. Ophthalm Epidemiol 2005;12:271–7.

Age-Related Eye Disease Study Research Group. Cognitive impairment in the Age-Related Eye Disease Study. AREDS report no. 16. Arch Ophthalmol 2006;124:537–43.

Age-Related Eye Disease Study Research Group. The Age-Related Eye Disease Study severity scale for age-related macular degeneration. AREDS report no. 17. Arch Ophthalmol 2005;123:1484–98.

Age-Related Eye Disease Study Research Group. A simplified severity scale for age-related macular degeneration. AREDS report no. 18. Arch Ophthalmol 2005;123:1570–4.

Age-Related Eye Disease Study Research Group. Risk factors for the incidence of advanced age-related macular degeneration in the Age-Related Eye Disease Study (AREDS). AREDS report no. 19. Ophthalmology 2005;112:533–9.

Age-Related Eye Disease Study Research Group. The relationship of dietary lipid intake and age-related macular degeneration in a case-control study. AREDS report no. 20. Arch Ophthalmol 2007;126:671–9.

Age-Related Eye Disease Study Research Group. Centrum use and progression of age-related cataract in the Age-Related Eye Disease Study (AREDS). AREDS report no. 21. Ophthalmology 2006;113:1264–70.

Age-Related Eye Disease Study Research Group. The relationship of dietary carotenoid and vitamin A, E, and C intake with age-related macular degeneration in a case-control study. AREDS report no. 22. Arch Ophthalmol 2007;123:1225–32.

SanGiovanni JP, Chew EY, Agron E, et al for the Age-Related Eye Disease Study Research Group. The relationship of dietary ω-3 long-chain polyunsaturated fatty acid intake with incident age-related macular degeneration. AREDS report no. 23. Arch Ophthalmol 2008;126(9):1274–9.

Chew EY, Sperduto RD, Milton RC, et al. Risk of advanced age-related macular degeneration after cataract surgery in the Age-Related Eye Disease Study. AREDS report 25. Ophthalmology 2009;116:297–303.

AREDS Research Group. Change in area of geographic atrophy in the Age-Related Eye Disease Study. AREDS report number 26. Arch Ophthalmol 2009;127:1168–74.

Forooghian F, Agron E, Clemons TE, et al. for the AREDS Research Group. Visual acuity outcomes after cataract surgery in patients with age-related macular degeneration: Age-Related Eye Disease Study report no. 27. Ophthalmology 2009;116:2093–100.

Cukras C, Agron E, Klein ML, et al. for the Age-Related Eye Disease Study Research Group. Natural history of drusenoid pigment epithelial detachment in age-related macular degeneration: Age-Related Eye Disease Study report no. 28. Ophthalmology 2010;117:489–99.

Hubbard LD, Danis RP, Neider MW, et al., Age-Related Eye Disease 2 Research Group. Brightness, contrast, and color balance of digital versus film retinal images in the Age-Related Eye Disease Study 2. Invest Ophthalmol Vis Sci 2008;49:3269–82.

Complications of AMD Prevention Trial (CAPT)

CAPT was a multicenter randomized trial designed to evaluate low-intensity laser treatment as a method of preventing vision loss among patients at risk of choroidal neovascularization and other manifestations of advanced age-related macular degeneration due to having large drusen in both eyes. CAPT was sponsored by the National Eye Institute and was preceded by a pilot study, the Choroidal Neovascularization Prevention Trial (CNVPT).

Choroidal Neovascularization Prevention Trial Research Group. Laser treatment in eyes with large drusen: short-term effects seen in a pilot randomized clinical trial. Ophthalmology 1998;105:11–23.

Although choroidal neovascularization developed with low frequency among both treated and untreated eyes in the Bilateral Drusen Study, it developed in more treated eyes in the Fellow Eye Study: 10 of 59 treated eyes versus two of 59 untreated eyes.

Choroidal Neovascularization Prevention Trial Research Group. Choroidal neovascularization in the Choroidal Neovascularization Prevention Trial. Ophthalmology 1998;105:1364–72.

Kaiser RS, Berger JW, Maguire MG, et al. Laser burn intensity and the risk for choroidal neovascularization in the CNVPT fellow eye study. Arch Ophthalmol 2001;119:826–32.

Choroidal Neovascularization Prevention Trial Research Group. Laser treatment in fellow eyes with large drusen: updated findings from a pilot randomized clinical trial. Ophthalmology 2003;110:971–8.

By 4 years of follow-up, the cumulative incidence of choroidal neovascularization in treated and untreated eyes was similar. The highest risk in treated eyes was during the first 1–2 years after prophylactic laser.

Complications of Age-related Macular Degeneration Prevention Trial Study Group. Complications of Age-related Macular Degeneration Prevention Trial (CAPT): rationale, design and methodology. Clin Trials 2004;1:91–107.

Complications of Age-related Macular Degeneration Prevention Trial Research Group. Baseline characteristics, the 25-item National Eye Institute Visual Functioning Questionnaire, and their associations in the Complications of Age-related Macular Degeneration Prevention Trial (CAPT). Ophthalmology 2004;111:1307–16.

Complications of Age-related Macular Degeneration Prevention Trial Research Group. Laser treatment in patients with bilateral large drusen. Ophthalmology 2006;113:1974–86.

Maguire MG, Alexander J, Fine SL and the Complications of Age-related Macular Degeneration Prevention Trial (CAPT) Research Group. Characteristics of choroidal neovascularization in the Complications of Age-related Macular Degeneration Prevention Trial. Ophthalmology 2008;115:1468–73.

Complications of Age-related Macular Degeneration Prevention Trial (CAPT) Research Group. Risk factors for choroidal neovascularization and geographic atrophy in the Complications of Age-related Macular Degeneration Prevention Trial. Ophthalmology 2008;115:1474–9.

Ying G, Maguire MG, Liu C, et al. for the Complications of Age-related Macular Degeneration Prevention Trial Research Group. Night vision symptoms and progression of age-related macular degeneration in the Complications of Age-related Macular Degeneration Prevention Trial. Ophthalmology 2008;115:1876–82.

Ying G, Maguire MG, Alexander J, et al. for the Complications of Age-related Macular Degeneration Prevention Trial (CAPT) Research Group. Description of the Age-related Eye Disease Study 9-step severity scale applied to participants in the Complications of Age-related Macular Degeneration Prevention Trial. Arch Ophthalmol 2009;127:1147–51.

Maguire MG, Ying G, McCannel CA. et al. for the Complications of Age-related Macular Degeneration Prevention Trial (CAPT) Research Group. Statin use and the incidence of advanced age-related macular degeneration in the Complications of Age-related Macular Degeneration Prevention Trial. Ophthalmology 2009;116:2381–5.

Ying G, Maguire MG for the Complications of Age-related Macular Degeneration Prevention Trial Research Group. Development of a risk score for geographic atrophy in [the] Complications of Age-related Macular Degeneration Prevention Trial. Ophthalmology 2011;118:332–8.

Other trials of potential preventive treatment for age-related macular degeneration and a Cochrane systematic review

Olk RJ, Friberg TR, Stickney KL, et al. Therapeutic benefits of infrared (810-nm) diode laser macular grid photocoagulation in prophylactic treatment of neoexudative age-related macular degeneration. Two-year results of a randomized pilot study. Ophthalmology 1999;106:2082–90.

Friberg TR, Musch DC, Lim JI, et al. PTAMD Study Group. Prophylactic Treatment of Age-related Macular Degeneration report number 1: 810-nanometer laser to eyes with drusen. Unilaterally eligible patients. Ophthalmology 2006;113:612–22.

Christen WG, Manson JE, Glynn RJ, et al. Beta carotene supplementation and age-related maculopathy in a randomized trial of US physicians. Arch Ophthalmol 2007;125:333–9.

Christen WG, Glynn RJ, Chew EY, et al. Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women. The Women’s Antioxidant and Folic Acid Cardiovascular Study. Arch Intern Med 2009;169:335–41.

Christen WG, Glynn RJ, Chew EY, et al. Vitamin E and age-related macular degeneration in a randomized trial of women. Ophthalmology 2010;117:1163–8.

Owens SL, Bunce C, Brannon AJ, et al. and the Drusen Laser Study Group. Prophylactic laser treatment hastens choroidal neovascularization in unilateral age-related maculopathy: Final results of the Drusen Laser Study. Am J Ophthalmol 2006;141:276–81.

Parodi MB, VIrgili G, Evans JR. Laser treatment of drusen to prevent progression to advanced age-related macular degeneration. Cochrane Database of Systematic Reviews 2009, Issue 3, Art. No.: CD006537. DOI: 10.1002/14651858.CD006537.pub2.

Retinopathy of prematurity

Initiation of the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) was stimulated by an increase in the incidence of retinopathy of prematurity following a decline after early clinical trials demonstrated that exposure to 100% oxygen in incubators had been responsible for the epidemic of retinopathy of prematurity in the USA in the 1950s. Increased incidence in the 1970s and 1980s was attributable to advances in neonatal medicine that had increased survival among very-low-birthweight premature infants. CRYO-ROP was designed to determine the safety and efficacy of transscleral cryotherapy of the peripheral retina in selected low-birthweight infants with retinopathy of prematurity and to study the natural history of retinal vessel development and outcome in such children. Following completion of CRYO-ROP, three additional trials were undertaken to evaluate proposed approaches to reduce the complications of retinopathy of prematurity, all with sponsorship by the National Eye Institute, either alone or in collaboration with other institutes of the National Institutes of Health. Findings from these trials are discussed in Chapter 61 (Pediatric retinal vascular diseases) and Chapter 114 (Retinopathy of prematurity).

Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP)

Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of Cryotherapy for Retinopathy of Prematurity: preliminary results. Arch Ophthalmol 1988;106:471–9.

Among eyes of infants assigned to cryotherapy, 22% versus 43% of eyes assigned to observation had a posterior retinal detachment, retinal fold involving the macula, or retrolental tissue.

Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of Cryotherapy for Retinopathy of Prematurity: preliminary results. Pediatrics 1988;81:697–706.

This article is a coordinated duplicate publication of the above findings.

Phelps DL, Phelps CE. Cryotherapy in infants with retinopathy of prematurity. A decision model for treating one or both eyes. JAMA 1989;261:1751–6.

Palmer EA. Results of US randomized clinical trial of cryotherapy for ROP (CRYO-ROP). Doc Ophthal 1990;74:245–51.

Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of Cryotherapy for Retinopathy of Prematurity: three-month outcome. Arch Ophthalmol 1990;108:195–204.

Three-month outcomes from the randomized trial for all 260 infants enrolled update the 1988 preliminary report on effectiveness of transscleral cryotherapy. Eyes treated with cryotherapy had reduced risk of posterior retinal detachment, retinal fold involving the macula, or retrolental tissue compared to untreated eyes: 31% versus 51% respectively.

Watzke RC, Robertson JE, Palmer EA, et al. Photographic grading in the Retinopathy of Prematurity Cryotherapy trial. Arch Ophthalmol 1990;108:950–5.

Dobson V, Quinn GE, Biglan AW, et al. Acuity card assessment of visual function in the Cryotherapy for Retinopathy of Prematurity trial. Invest Ophthalmol Vis Sci 1990;31:1702–8.

Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of Cryotherapy for Retinopathy of Prematurity: One-year outcome – structure and function. Arch Ophthalmol 1990;108:1408–16.

After 1 year of follow-up, eyes assigned to transscleral cryotherapy had reduced risk of posterior retinal detachment, retinal fold involving the macula, or retrolental tissue compared to untreated eyes: 26% versus 47%, respectively. Assessment of grating visual acuity using the Teller Acuity Card correlated with retinal findings: 35% of eyes treated with cryotherapy versus 56% of eyes not treated had an unfavorable functional outcome at 1 year.

Palmer EA, Hardy RJ, Davis BR, et al. Operational aspects of terminating randomization in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity. Control Clin Trials 1991;12:277–92.

Hardy RJ, Davis BR, Palmer EA, et al. Statistical considerations in terminating randomization in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity. Control Clin Trials 1991;12:293–303.

Palmer EA, Flynn JT, Hardy RJ, et al. Incidence and early course of retinopathy of prematurity. Ophthalmology 1991;98:1628–40.

Phelps DL, Brown DR, Tung B, et al. 28-day survival rates of 6676 neonates with birth weights of 1250 grams or less. Pediatrics 1991;87:7–17.

Quinn GE, Dobson V, Barr CC, et al. Visual acuity in infants after vitrectomy for severe retinopathy of prematurity. Ophthalmology 1991;98:5–13.

Gilbert WS, Dobson V, Quinn GE, et al. The correlation of visual function with posterior retinal structure in severe retinopathy of prematurity. Arch Ophthalmol 1992;110:625–31.

Summers G, Phelps DL, Tung B, et al. Ocular cosmesis in retinopathy of prematurity. Arch Ophthalmol 1992;110:1092–7.

Evans MS, Wallace PR, Palmer EA. Fundus photography in infants. J Ophthalm Photo 1993;15:38–9.

Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of Cryotherapy for Retinopathy of Prematurity: 3-year outcome – structure and function. Arch Ophthalmol 1993;111:339–44.

Reynolds J, Dobson V, Quinn GE, et al. Prediction of visual function in eyes with mild to moderate posterior pole residua of retinopathy of prematurity. Arch Ophthalmol 1993;111:1050–6.

Schaffer DB, Palmer EA, Plotsky DF, et al. Prognostic factors in the natural course of retinopathy of prematurity. Ophthalmology 1993;100:230–7.

Cryotherapy for Retinopathy of Prematurity Cooperative Group. The natural ocular outcome of premature birth and retinopathy. Status at 1 year. Arch Ophthalmol 1994;112:903–12.

Dobson V, Quinn GE, Summers CG, et al. Effect of acute-phase retinopathy of prematurity on grating acuity development in the very low birth weight infant. Invest Ophthalmol Vis Sci 1994;35:4236–44.

Quinn GE, Dobson V, Biglan A, et al. Correlation of retinopathy of prematurity in fellow eyes in the Cryotherapy for Retinopathy of Prematurity study. Arch Ophthalmol 1995;113:469–73.

Dobson V, Quinn GE, Saunders RA, et al. Grating visual acuity in eyes with retinal residua of retinopathy of prematurity. Arch Ophthalmol 1995;113:1172–7.

Dobson V, Quinn GE, Tung B, et al. Comparison of recognition and grating acuities in very-low-birth-weight children with and without retinal residua of retinopathy of prematurity. Invest Ophthalmol Vis Sci 1995;36:692–702.

Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of Cryotherapy for Retinopathy of Prematurity: Snellen visual acuity and structural outcome at years after randomization. Arch Ophthalmol 1996;114:417–24.

Kivlin JD, Biglan AW, Gordon RA, et al. Early retinal vessel development and iris vessel dilation as factors in retinopathy of prematurity. Arch Ophthalmol 1996;114:150–4.

Quinn GE, Dobson V, Barr CC, et al. Visual acuity of eyes after vitrectomy for retinopathy of prematurity: follow-up at years. Ophthalmology 1996;103:595–600.

Gilbert WS, Quinn GE, Dobson V, et al. Partial retinal detachment at 3 months after threshold retinopathy of prematurity. Long-term structural and functional outcome. Arch Ophthalmol 1996;114:1085–91.

Quinn GE, Dobson V, Hardy RJ, et al. Visual fields measured with double-arc perimetry in eyes with threshold retinopathy of prematurity from the Cryotherapy for Retinopathy of Prematurity trial. Ophthalmology 1996;103:1432–7.

Dobson V, Quinn GE, Abramov I, et al. Color vision measured with pseudoisochromatic plates at five-and-a-half years in eyes of children from the CRYO-ROP study. Invest Ophthalmol Vis Sci 1996;37:2467–74.

Bartholomew PA, Chao J, Evans JL, et al. Acceptance/use of the teller acuity card procedure in the clinic. Am Orthop J 1996;46:99–105.

Saunders RA, Donahue ML, Christmann LM, et al. Racial variation in retinopathy of prematurity. Arch Ophthalmol 1997;115:604–8.

Bremer DL, Palmer EA, Fellows RR, et al. Strabismus in premature infants in the first year of life. Arch Ophthalmol 1998;116:329–33.

Quinn GE, Dobson V, Kivlin J, et al. Prevalence of myopia between 3 months and years in preterm infants with and without retinopathy of prematurity. Ophthalmology 1998;105:1292–300.

Repka MX, Summers CG, Palmer EA, et al. The incidence of ophthalmologic interventions in children with birth weights less than 1251 grams. Results through years. Ophthalmology 1998;105:1621–7.

Dobson V, Quinn GE, Siatkowski RM, et al. Agreement between grating acuity at age 1 year and Snellen acuity at age years in the preterm child. Invest Ophthalmol Vis Sci 1999;40:496–503.

Harvey EM, Dobson V, Tung B, et al. Interobserver agreement for grating acuity and letter acuity assessment in 1- to -year-olds with severe retinopathy of prematurity. Invest Ophthalmol Vis Sci 1997;40:1565–76.

Repka MX, Palmer EA, Tung B, et al. Involution of retinopathy of prematurity. Arch Ophthalmol 2000;118:645–9.

Quinn GE, Dobson V, Siatkowski RM, et al. Does cryotherapy affect refractive error? Results from treated versus control eyes in the Cryotherapy for Retinopathy of Prematurity trial. Ophthalmology 2001;108:343–7.

Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of Cryotherapy for Retinopathy of Prematurity: ophthalmological outcomes at 10 years. Arch Ophthalmol 2001;119:1110–8.

Cryotherapy for Retinopathy of Prematurity Cooperative Group. Effect of retinal ablative therapy for threshold retinopathy of prematurity: results of Goldmann perimetry at the age of 10 years. Arch Ophthalmol 2001;119:1120–5.

Cryotherapy for Retinopathy of Prematurity Cooperative Group. Contrast sensitivity at age 10 years in children who had threshold retinopathy of prematurity. Arch Ophthalmol 2001;119:1129–33.

Editorial Committee for the Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter Trial of Cryotherapy for Retinopathy of Prematurity. Natural history of ROP: ocular outcome at years in premature infants with birth weights less than 1251 g. Arch Ophthalmol 2002;120:595–9.

Hardy RJ, Palmer EA, Dobson V, et al. Risk analysis of prethreshold retinopathy of prematurity. Arch Ophthalmol 2003;121:1697–701.

Cryotherapy for Retinopathy of Prematurity Cooperative Group. 15-year outcomes following threshold retinopathy of prematurity. Final results from the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity. Arch Ophthalmol 2005;123:311–8.

Cryotherapy for Retinopathy of Prematurity Cooperative Group. Visual acuity at 10 years in Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) Study eyes. Arch Ophthalmol 2006;124:199–202.

Multicenter Study of Light Reduction in Retinopathy of Prematurity (LIGHT-ROP)

Reynolds JD, Hardy RJ, Kennedy KA, et al. Lack of efficacy of light reduction in preventing retinopathy of prematurity. N Engl J Med 1998;338:1572–6.

Reduced nursery lighting did not decrease the incidence of retinopathy of prematurity compared to normal nursery lighting among premature infants with birth weights of 1250 g or less in this randomized trial.

LIGHT-ROP Cooperative Group. The design of the multicenter study of Light Reduction in Retinopathy of Prematurity (LIGHT-ROP). J Pediatr Ophthalmol Strabismus 1999;36:257–63.

Kennedy KA, Fielder AR, Hardy RJ, et al. Reduced lighting does not improve medical outcomes in very-low-birth-weight infants. J Pediatr 2001;139:527–31.

Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity (STOP-ROP)

STOP-ROP Multicenter Study Group. Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity (STOP-ROP), a randomized, controlled trial. I: Primary outcomes. Pediatrics 2000;105:295–310.

Premature infants with prethreshold disease and median pulse oximetry less than 94% saturation were randomly assigned to conventional oxygen with pulse oximetry targeted at 89–94% saturation or supplemental oxygen with pulse oximetry targeted at 96–99% saturation. No substantive difference in rates of progression was found.

Oden NL, Phelps DL, the STOP-ROP Multicenter Study Group. Statistical issues related to early closure of STOP-ROP, a group-sequential trial. Control Clin Trials 2003;24:28–38.

Early Treatment of Retinopathy for Prematurity (ETROP or EARLY-ROP)

Early Treatment for Retinopathy of Prematurity Cooperative Group. Revised indications for the treatment of retinopathy of prematurity. Results of the Early Treatment for Retinopathy of Prematurity randomized trial. Arch Ophthalmol 2003;121:1684–96.

Early treatment with peripheral retinal ablation reduced unfavorable outcomes with respect to both visual acuity and structure in comparison to standard management of prethreshold retinopathy of prematurity in this randomized trial.

Hardy RJ, Good WV, Dobson V, et al. for the Early Treatment for Retinopathy of Prematurity Cooperative Group. Multicenter trial of early treatment for retinopathy of prematurity: Study design. Control Clin Trials 2004;24:311–26.

Davitt BV, Dobson V, Good WV, et al. for the Early Treatment for Retinopathy of Prematurity Cooperative Group. Prevalence of myopia at 9 months in infants with high-risk prethreshold retinopathy of prematurity. Ophthalmology 2005;112:1564–8.

Repka MX, Tung B, Good WV, et al. Outcome of eyes developing retinal detachment during the Early Treatment for Retinopathy of Prematurity Study (ETROP). Arch Opthalmol 2006;124:24–30.

VanderVeen DK, Coats DK, Dobson V, et al. for the Early Treatment for Retinopathy of Prematurity Cooperative Group. Prevalence and course of strabismus in the first year of life for infants with prethreshold retinopathy of prematurity. Arch Ophthalmol 2006;124:766–73.

Early Treatment for Retinopathy of Prematurity Cooperative Group. The Early Treatment for Retinopathy of Prematurity Study: structural findings at age 2 years. Br J Ophthalmol 2006;90:1378–82.

Quinn GE, Dobson V, Davitt BV, et al. on behalf of the Early Treatment for Retinopathy of Prematurity Cooperative Group. Progression of myopia and high myopia in the Early Treatment for Retinopathy of Prematurity Study. Findings to 3 years of age. Ophthalmology 2008;115:1058–64.

Early Treatment for Retinopathy of Prematurity Cooperative Group. Final visual acuity results in the Early Treatment for Retinopathy of Prematurity Study. Arch Ophthalmol 2010;128:663–71.

Early Treatment for Retinopathy of Prematurity Cooperative Group. Visual field extent at 6 years of age in children who had high-risk prethreshold retinopathy of prematurity. Arch Ophthalmol 2011;129:127–32.

Early Treatment for Retinopathy of Prematurity Cooperative Group. Grating visual acuity results in the Early Treatment for Retinopathy of Prematurity Study. Arch Ophthalmol 2011;129:840–6.

Other retinal and retina-related conditions

Collaborative Ocular Melanoma Study (COMS)

The COMS was designed and conducted to evaluate radiotherapy for treatment of choroidal melanoma, either in comparison to enucleation (COMS randomized trial of iodine-125 brachytherapy) or in combination with enucleation (COMS randomized trial of pre-enucleation radiation). Both US and Canadian centers participated in the COMS. In addition, a nonrandomized observational study of small choroidal melanoma was conducted at a subset of COMS centers. A parallel prospective study of quality of life among patients in the brachytherapy trial (COMS-QOLS) was conducted as well. The COMS was sponsored by the National Eye Institute and the National Cancer Institute, National Institutes of Health, US Department of Health and Human Services. The COMS design and findings are discussed in detail in Chapter 150 (Collaborative Ocular Melanoma Study), which cites most publications from the COMS; only primary outcome publications are cited here.

Collaborative Ocular Melanoma Study Group. The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre-enucleation radiation of large choroidal melanoma. II: Initial mortality findings. COMS report no. 10. Am J Ophthalmol 1998;125:779–96.

Five-year survival rates were 62% for patients assigned to pre-enucleation radiation and 57% for patients who had enucleation only. Five-year rates of death with histopathologically confirmed melanoma were 26% and 28%, respectively.

Collaborative Ocular Melanoma Study Group. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, III: Initial mortality findings. COMS report no. 18. Arch Ophthalmol 2001;119:969–82.

Among the 1317 patients enrolled in this COMS trial, 5-year all-cause mortality rates were 19% among those assigned to enucleation and 18% among those assigned to brachytherapy. Five-year rates of death with confirmed melanoma metastasis were 11% in the enucleation arm and 9% in the brachytherapy arm.

Collaborative Ocular Melanoma Study Group. The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre-enucleation radiation of large choroidal melanoma. IV. Ten-year mortality findings and prognostic factors. COMS report no. 24. Am J Ophthalmol 2004;138:936–51.

Collaborative Ocular Melanoma Study – Quality of Life Study Group. Quality of life after I-125 brachytherapy versus enucleation for choroidal melanoma: 5-year results from the Collaborative Ocular Melanoma Study. COMS-QOLS report no. 3. Arch Ophthalmol 2006;124:226–36.

Collaborative Ocular Melanoma Study Group. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma. V. Twelve-year mortality rates and prognostic factors. COMS report no. 28. Arch Ophthalmol 2006;124:1684–93.

Studies of the Ocular Complications of AIDS (SOCA)

In order to address issues regarding treatment of eye involvement, primarily cytomegalovirus retinitis, in patients with the acquired immune deficiency syndrome (AIDS), the National Eye Institute has sponsored SOCA, a clinical trials network. Most of the SOCA clinical trials have been conducted in collaboration with the AIDS Clinical Trials Group. Several of the trials also have had industry sponsorship. Accrual of patients to the first SOCA trial began in March 1990. Clinical applications of SOCA findings are discussed in Chapter 81 (HIV-Associated Infections). A longitudinal observational study (LSOCA) was undertaken by the SOCA investigators to provide information on ocular complications during the HAART era.

Studies of Ocular Complications of AIDS (SOCA) Research Group, in collaboration with the AIDS Clinical Trials Group (ACTG). Studies of Ocular Complications of AIDS foscarnet–ganciclovir cytomegalovirus retinitis trial: 1. Rationale, design, and methods. Control Clin Trials 1992;13:22–39.

Studies of Ocular Complications of AIDS Research Group, in collaboration with the AIDS Clinical Trials Group. Mortality in patients with the acquired immunodeficiency syndrome treated with either foscarnet or ganciclovir for cytomegalovirus retinitis. N Engl J Med 1992;326:213–20.

After 19 months of treatment, the rate of mortality in the ganciclovir group was 77% higher than in the foscarnet group, leading to suspension of the treatment protocol.

Studies of Ocular Complications of AIDS Research Group in collaboration with the AIDS Clinical Trials Group. Foscarnet–ganciclovir cytomegalovirus retinitis trial: 4. Visual outcomes. Ophthalmology 1994;101:1250–61.

At 6 months after randomization, visual outcomes were similar, with 88% of the forscarnet-assigned patients and 93% of the ganciclovir-assigned patients having a best-corrected visual acuity of 20/40 or better.

Studies of Ocular Complications of AIDS Research Group in collaboration with the AIDS Clinical Trials Group. Morbidity and toxic effects associated with ganciclovir or foscarnet therapy in a randomized cytomegalovirus retinitis trial. Arch Intern Med 1995;155:65–74.

Studies of Ocular Complications of AIDS Research Group, in collaboration with the AIDS Clinical Trials Group. Antiviral effects of foscarnet and ganciclovir therapy on human immunodeficiency virus p24 antigen in patients with AIDS and cytomegalovirus retinitis. J Infect Dis 1995;172:613–21.

Studies of Ocular Complications of AIDS Research Group, in collaboration with the AIDS Clinical Trials Group. Combination foscarnet and ganciclovir therapy vs monotherapy for the treatment of relapsed cytomegalovirus retinitis in patients with AIDS: the Cytomegalovirus Retreatment trial. Arch Ophthalmol 1996;114:23–33.

Combination therapy with foscarnet and ganciclovir decreased the rate of visual field loss and the rate of increase in retinal area involvement.

Studies of Ocular Complications of AIDS Research Group, in collaboration with the AIDS Clinical Trials Group. Clinical vs photographic assessment of treatment of cytomegalovirus retinitis: Foscarnet–Ganciclovir Cytomegalovirus Retinitis Trial report 8. Arch Ophthalmol 1996;114:848–55.

Wu AW, Coleson LC, Holbrook J, et al. Measuring visual function and quality of life in patients with cytomegalovirus retinitis: development of a questionnaire. Arch Ophthalmol 1996;114:841–7.

Studies of Ocular Complications of AIDS Research Group, in collaboration with the AIDS Clinical Trials Group. Assessment of cytomegalovirus retinitis: clinical evaluation vs centralized grading of fundus photographs. Arch Ophthalmol 1996;114:791–805.

Studies of Ocular Complications of AIDS Research Group, in collaboration with the AIDS Clinical Trials Group. MSL-109 adjuvant therapy for cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome: the Monoclonal Antibody Cytomegalovirus Retinitis Trial. Arch Ophthalmol 1997;115:1528–36. [Correction in Arch Ophthalmol 1998;116:296.]

Studies of Ocular Complications of AIDS Research Group, in collaboration with the AIDS Clinical Trials Group. Parenteral cidofovir for cytomegalovirus retinitis in patients with AIDS: the HPMPC Peripheral Cytomegalovirus Retinitis trial. A randomized, controlled trial. Ann Intern Med 1997;126:264–74.

Both low and high doses of cidofovir slowed progression of cytomegalovirus retinitis to medians of 64 and 21 days, respectively.

Studies of Ocular Complications of AIDS (SOCA) Research Group, in collaboration with the AIDS Clinical Trials Group (ACTG). Rhegmatogenous retinal detachment in patients with cytomegalovirus retinitis: the Foscarnet–Ganciclovir Cytomegalovirus Retinitis trial. Am J Ophthalmol 1997;124:61–70.

Studies of Ocular Complications of AIDS Research Group in collaboration with the AIDS Clinical Trials Group. Foscarnet–Ganciclovir Cytomegalovirus Retinitis Trial: 5. Clinical features of cytomegalovirus retinitis at diagnosis. Am J Ophthalmol 1997;124:141–57.

Studies of Ocular Complications of AIDS Research Group, in collaboration with the AIDS Clinical Trials Group. Cytomegalovirus (CMV) culture results, drug resistance, and clinical outcome in AIDS patients with CMV treated with either foscarnet or ganciclovir. J Infect Dis 1997;176:50–8.

Holbrook JT, Davis MD, Hubbard LD, et al. Risk factors for advancement of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome. Arch Ophthalmol 2000;118:1196–204.

Holbrook JT, Meinert CL, Van Natta ML, et al. Photographic measures of cytomegalovirus retinitis as surrogates for visual outcomes in treated patients. Arch Ophthalmol 2001;119:554–63.

Martin BK, Gilpin AMK, Jabs DA, et al. for the Studies of Ocular Complications of AIDS Research Group. Reliability, validity, and responsiveness of general and disease-specific quality of life measures in a clinical trial for cytomegalovirus retinitis. J Clin Epidemiol 2001;54:376–86.

Studies of Ocular Complications of AIDS Research Group in collaboration with the AIDS Clinical Trials Group. The ganciclovir implant plus oral ganciclovir versus parenteral cidofovir for the treatment of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome: The Ganciclovir Cidofovir Cytomegalovirus Retinitis Trial. Am J Ophthalmol 2001;131:457–67.

Jabs DA, Gilpin AMK, Min Y-I, et al. for the Studies of Ocular Complications of AIDS Research Group. HIV and cytomegalovirus viral load and clinical outcomes in AIDS and cytomegalovirus retinitis patients: Monoclonal Antibody Cytomegalovirus Retinitis Trial. AIDS 2002;16:877–87.

Holbrook JT, Jabs DA, Weinberg DV, et al. for the Studies of Ocular Complications of AIDS (SOCA) Research Group. Visual loss in patients with cytomegalovirus retinitis and acquired immunodeficiency syndrome before widespread availability of highly active antiretroviral therapy. Arch Ophthalmol 2003;121:99–107.

Dunn JP, Van Natta M, Foster G, et al for the Studies of Ocular Complications of AIDS Research Group. Complications of ganciclovir implant surgery in patients with cytomegalovirus retinitis. The Ganciclovir Cidofovir Cytomegalovirus Retinitis Trial. Retina 2004;24:41–50.

Jabs DA, Van Natta M, Thorne JE, et al. for the Studies of the Ocular Complications of AIDS Research Group. Course of cytomegalovirus retinitis in the era of highly active antiretroviral therapy. I. Retinitis progression. Ophthalmology 2004;111:2224–31.

Jabs DA, Van Natta M, Thorne JE, et al. for the Studies of the Ocular Complications of AIDS Research Group. Course of cytomegalovirus retinitis in the era of highly active antiretroviral therapy. 2. Second eye involvement and retinal detachment. Ophthalmology 2004;111:2232–9.

Kempen JH, Min Y-I, Freeman WR, et al. for the Studies of the Ocular Complications of AIDS Research Group. Risk of immune recovery uveitis in patients with AIDS and cytomegalovirus retinitis. Ophthalmology 2006;113:684–94.

Thorne JE, Jabs DA, Kempen JH, et al. for the Studies of Ocular Complications of AIDS Research Group. Incidence of and risk factors for visual acuity loss among patients with AIDS and cytomegalovirus retinitis in the era of highly active antiretroviral therapy. Ophthalmology 2006;113:1432–40.

Thorne JE, Jabs DA, Kempen JH, et al. for the Studies of Ocular Complications of AIDS Research Group. Causes of visual acuity loss among patients with AIDS and cytomegalovirus retinitis in the era of highly active antiretroviral therapy. Ophthalmology 2006;113:1441–5.

Trials of treatment of posterior uveitis

Callanan DG, Jaffe GJ, Marin DF, et al. Treatment of posterior uveitis with a fluocinolone acetonide implant. Three-year clinical trial results. Arch Ophthalmol 2008;126:1191–201.

Lowder C, Belfort B, Lightman S, et al. Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis. Arch Ophthalmol 2011;129:545–53.

Soheilian M, Ramezani A, Azimzadeh A, et al. Randomized trial of intravitreal clindamycin and dexamethasone versus pyrimethamine, sulfadiazine, and prednisolone in treatment of ocular toxoplasmosis. Ophthalmology 2011;118:134–41.

Silicone Study

The Silicone Study was conducted to compare postoperative tamponade effectiveness of intraocular silicone oil with that of long-acting gas for managing retinal detachment complicated by proliferative vitreoretinopathy. The Silicone Study was sponsored by the National Eye Institute. Clinical application of findings from the Silicone Study is discussed in Chapter 104 (Special adjuncts to treatment).

Azen SP, Irvine AR, Davis MD, et al. The validity and reliability of photographic documentation of proliferative vitreoretinopathy. Ophthalmology 1989;96:352–7.

Lean JS, Stern WH, Irvine AR, et al. Classification of proliferative vitreoretinopathy used in the Silicone Study. Ophthalmology 1989;96:765–71.

Azen SP, Boone DC, Barlow W, et al. Methods, statistical features, and baseline results of a standardized, multicentered ophthalmological surgical trial: the Silicone Study. Control Clin Trials 1991;12:438–55.

Silicone Study Group. Vitrectomy with silicone oil or sulfur hexafluoride gas in eyes with severe proliferative vitreoretinopathy: results of a randomized clinical trial. Silicone Study Report 1. Arch Ophthalmol 1992;110:770–9.

After 24 months of follow-up, more eyes assigned to silicone oil than assigned to sulfur hexafluoride gas had visual acuity of 5/200 or better. Macular attachment was achieved more often in eyes treated with silicone oil.

Silicone Study Group. Vitrectomy with silicone oil or perfluoropropane gas in eyes with severe proliferative vitreoretinopathy: results of a randomized clinical trial. Silicone Study Report 2. Arch Ophthalmol 1992;110:780–92.

McCuen BW, Azen SP, Stern W, et al. Vitrectomy with silicone oil or with perfluoropropane gas in eyes with severe proliferative vitreoretinopathy. Silicone Study Report No. 3. Retina 1993;13:279–84.

Barr CC, Lai MY, Lean JS, et al. Postoperative intraocular pressure abnormalities in the Silicone Study. Silicone Study report 4. Ophthalmology 1993;100:1629–35.

Blumenkranz MS, Azen SP, Aaberg T, et al. Relaxing retinotomy with silicone oil or long-acting gas in eyes with severe proliferative vitreoretinopathy. Silicone Study Report 5. Am J Ophthalmol 1993;116:557–64.

Hutton WL, Azen SP, Blumenkranz MS, et al. The effects of silicone oil removal. Silicone Study Report 6. Arch Ophthalmol 1994;112:778–85.

Abrams GW, Azen SP, Barr CC, et al. The incidence of corneal abnormalities in the Silicone Study. Silicone Study report 7. Arch Ophthalmol 1995;113:764–9.

Cox MS, Azen SP, Barr CC, et al. Macular pucker after successful surgery for proliferative vitreoretinopathy. Silicone Study report 8. Ophthalmology 1995;102:1884–91.

Lean J, Azen SP, Lopez PF, et al. The prognostic utility of the Silicone Study classification system. Silicone Study report 9. Arch Ophthalmol 1996;114:286–92.

Diddie KR, Azen SP, Freeman HM, et al. Anterior proliferative vitreoretinopathy in the Silicone Study. Silicone Study report number 10. Ophthalmology 1996;103:1092–9.

Abrams GW, Azen SP, McCuen BW, et al. Vitrectomy with silicone oil or long-acting gas in eyes with severe proliferative vitreoretinopathy: results of additional and long-term follow-up. Silicone Study report 11. Arch Ophthalmol 1997;115:335–44.

Macular hole trials

Freeman WR, Azen SP, Kim JW, et al. Vitrectomy for the treatment of full-thickness stage 3 or 4 macular holes: results of a multicenter randomized clinical trial. Arch Ophthalmol 1997;115:11–21.

Although more adverse events occurred in eyes treated surgically, those eyes had higher rates of hole closure and improvement in visual acuity than observed eyes.

Tadayoni R, Vicaut E, Devin F, et al. A randomized controlled trial of alleviated positioning after small macular hole surgery. Ophthalmology 2011;118:150–5.

Retinitis pigmentosa

Berson EL, Rosner B, Sandberg MA, et al. A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa. Arch Ophthalmol 1993;111:761–72.

Sandberg MA, Weigel-DeFranco C, Rosner B, et al. The relationship between visual field size and electroretinogram amplitude in retinitis pigmentosa. Invest Ophthalmol Vis Sci 1996;37:1693–8.

Berson EL, Rosner B, Sandberg MA, et al. Clinical trial of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment. Arch Ophthalmol 2004;122:1297–305.

Berson EL, Rosner B, Sandberg MA, et al. Further evaluation of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment: subgroup analyses. Arch Ophthalmol 2004;122:1306–14.

Berson EL, Rosner B, Sandberg MA, et al. Clinical trial of lutein in patients with retinitis pigmentosa receiving vitamin A. Arch Ophthalmol 2010;128:403–11.

Adackapara CA, Sunness JS, DiBernardo CW, et al. Prevalence of cystoid macular edema and stability of OCT retinal thickness in eyes with retinitis pigmentosa during a 48-week lutein trial. Retina 2008;28:103–10.

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Retina-Related Clinical Trials: A Resource Bibliography

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