Treatment of macular diseases: an overview of key randomized clinical trials

Macular diseases are traditionally a serious issue in ophthalmology, which has great social impact due to widespread occurrence and significant vision loss, often irreversible. Over the past few decades, the possibilities for the diagnosis and treatment of pathologies of the retina and choroid have been significantly expanded. Randomized clinical trials provided ophthalmologists with valuable information on the natural course and treatment strategies of common retinal diseases from the viewpoint of evidence-based medicine. However, due to the large number of trials conducted, it is often difficult to make an adequate choice of data to be used in daily practice. In this review, we systematize the most valuable randomized clinical trials. To this end, we selected 42 randomized clinical studies conducted between 1979 and 2019 and focused on the treatment of age-related macular degeneration (AREDS 1, AREDS 2, ANCHOR, MARINA, PrONTO, CATT, IVAN, VIEW 1, VIEW 2, EVEREST II, PLANET, SEVEN-UP, ALTAIR, HAWK, HARRIER), choroidal neovascularization of multiple etiology (myopic, post-inflammatory, angioid-streak-related, etc. — RADIANCE, REPAIR, MYRROR, MINERVA), diabetic eye lesions (diabetic retinopathy and diabetic macular edema — ETDRS, DRCR.net Protocols B, I, S and T, RISE, RIDE, VIVID-DME, VISTA-DME, MEAD, FAME), retinal vein occlusions (BVOS, CVOS, SCORE-CRVO, SCORE-BRVO, BRAVO, CRUISE, GALILEO, COPERNICUS, VIBRANT), as well as retinopathy of prematurity (CRYO-ROP, ETROP, RAINBOW). The review summarizes the main results of these studies, which confirm the effectiveness and safety of such treatment methods as antiVEGF and photodynamic therapy, retinal laser photocoagulation, cryotherapy, corticosteroids and nutraceuticals from the viewpoint of evidence-based medicine. For greater clarity, we provide a table summarizing information on each of the randomized clinical trials considered.

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2. Age-Related Eye Disease Study 2 Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS 2) randomized clinical trial. JAMA. 2013; 309 (19): 2005–15. doi: 10.1001/jama.2013.4997

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5. Lalwani G.A., Rosenfeld P.J., Fung A.E., et al. A variable-dosing regimen with intravitreal ranibizumab for neovascular age-related macular degeneration: year 2 of the PrONTO Study. Am. J. Ophthalmol. 2009; 148 (1): 43–58.e41. doi: 10.1016/j.ajo.2009.01.024

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12. Rofagha S., Bhisitkul R.B., Boyer D.S., Sadda S.R., Zhang K. Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: a multicenter cohort study (SEVEN-UP). Ophthalmology. 2013; 120 (11): 2292–9. doi: 10.1016/j.ophtha.2013.03.046

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16. Wolf S., Balciuniene V.J., Laganovska G., et al. RADIANCE: a randomized controlled study of ranibizumab in patients with choroidal neovascularization secondary to pathologic myopia. Ophthalmology. 2014; 121 (3): 682–92.e2. doi: 10.1016/j.ophtha.2013.10.023

17. Tan N.W., Ohno-Matsui K., Koh H.J., et al. Long-term outcomes of ranibizumab treatment of myopic choroidal neovascularization in East-Asian patients from the RADIANCE study. Retina. 2018; 38 (11): 2228–38. doi: 10.1097/IAE.0000000000001858

18. Tufail A., Narendran N., Patel P.J., et al. Ranibizumab in myopic choroidal neovascularization: the 12-month results from the REPAIR study. Ophthalmology. 2013; 120 (9): 1944–5.e1. doi: 10.1016/j.ophtha.2013.06.010

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21. 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 (7): 761–74.

22. Early Treatment Diabetic Retinopathy Study Research Group. Effects of aspirin treatment on diabetic retinopathy. ETDRS report number 8. Ophthalmology. 1991; 98 (5 Suppl): 757–65.

23. Diabetic Retinopathy Clinical Research Network. A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology. 2008; 115 (9): 1447–9. doi: 10.1016/j.ophtha.2008.06.015

24. Elman M.J., Ayala A., Bressler N.M., et al. Intravitreal ranibizumab for diabetic macular edema with prompt versus deferred laser treatment: 5-year randomized trial results. Ophthalmology. 2015; 122 (2): 375–81. doi: 10.1016/j.ophtha.2014.08.047

25. Wells J.A., Glassman A.R., Ayala A.R., et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema: two-year results from a comparative effectiveness randomized clinical trial. Ophthalmology. 2016; 123 (6): 1351–9. doi: 10.1016/j.ophtha.2016.02.022

26. Gross J.G., Glassman A.R., Jampol L.M., et al. Panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. JAMA. 2015; 314 (20): 2137–46. doi: 10.1001/jama.2015.15217

27. Nguyen Q.D., Brown D.M., Marcus D.M., et al. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012; 119 (4): 789–801. doi: 10.1016/j.ophtha.2011.12.039

28. Korobelnik J.F., Do D.V., Schmidt-Erfurth U., et al. Intravitreal aflibercept for diabetic macular edema. Ophthalmology. 2014; 121 (11): 2247–54. doi: 10.1016/j.ophtha.2014.05.006

29. Boyer D.S., Yoon Y.H., Belfort R.Jr., et al. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. Ophthalmology. 2014; 121 (10): 1904–14. doi: 10.1016/j.ophtha.2014.04.024

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33. Ip M.S., Scott I.U., VanVeldhuisen P.C., et al. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with observation to treat vision loss associated with macular edema secondary to central retinal vein occlusion: the Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) study report 5. Arch. Ophthalmol. 2009; 127 (9): 1101–14. doi: 10.1001/archophthalmol.2009.234

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37. Korobelnik J.F., Holz F.G., Roider J., et al. Intravitreal aflibercept injection for macular edema resulting from central retinal vein occlusion: one-year results of the phase 3 GALILEO Study. Ophthalmology. 2014; 121 (1): 202–8. doi: 10.1016/j.ophtha.2013.08.012

38. Heier J.S., Clark W.L., Boyer D.S., et al. Intravitreal aflibercept injection for macular edema due to central retinal vein occlusion: two-year results from the COPERNICUS study. Ophthalmology. 2014; 121 (7): 1414–20. doi: 10.1016/j.ophtha.2014.01.027

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