13 Clinical Trials Summary
13.0 Introduction
13.1 Cornea
13.2 Cataract
13.3 Medical Retina – Age-Related Macular Degeneration (AMD)
13.4 Medical Retina - Diabetes
13.5 Medical Retina – Retinal Vein Occlusion (RVO)
13.6 Vitreoretinal Surgery
13.7 Glaucoma
13.8 Oculoplastics
13.9 Paediatrics
13.10 Neuro-Ophthalmology
13.11 Ocular Oncology
13.3 Medical Retina – Age-Related Macular Degeneration (AMD)
IVB = Bevacizumab, IVR = Ranibizumab, IVA = Aflibercept, IVTA = Triamcinolone, PDT = Photodynamic Therapy, PCV = Polypoidal Choroidal Vasculopathy
MPS [xiii]
Macular Photocoagulation Study
Laser decreased risk of vision loss by 15-30% for extra- and juxtafoveal CNV (cf. Observation), but high risk of recurrent CNV (~50%)
Fine, S.L. 1980. Macular Photocoagulation Study. Archives of Ophthalmology 98(5) 832-832.
TAP [xiv]
Treatment of classic AMD CNV with PDT
PDT halves risk of vision loss for subfoveal classic CNV (cf. observation)
No reduction in vision loss with minimally classic (i.e. < 50% classic)
Kaiser, P.K. 2006. Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: 5-year results of two randomized clinical trials with an open-label extension: TAP report no. 8. Graefes Arch Clin Exp Ophthalmol 244(9) 1132-1142
VIP [xv]
Treatment of occult AMD CNV with PDT
PDT reduces risk of vision loss by 40% for subfoveal purely occult CNV (cf. observation)
2001. 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 2. Am J Ophthalmol 131(5) 541-560.
ANCHOR [xvi,xvii]
Classic AMD CNV
Monthly IVR far superior to PDT for classic CNV
(95% maintain VA cf. 60% PDT; 40% gain 3 lines cf. 5% PDT) at 1 year
Brown, D.M., Michels, M., Kaiser, P.K. et al. 2009. Ranibizumab versus Verteporfin Photodynamic Therapy for Neovascular Age-Related Macular Degeneration: Two-Year Results of the ANCHOR Study. Ophthalmology 116(1) 57-65.e55.
Kaiser, P.K., Brown, D.M., Zhang, K. et al. 2007. Ranibizumab for Predominantly Classic Neovascular Age-related Macular Degeneration: Subgroup Analysis of First-year ANCHOR Results. American Journal of Ophthalmology 144(6) 850-857.e854.
MARINA [xviii,xix]
Occult AMD CNV
Monthly IVR far superior to observation for occult CNV
(95% maintain VA cf. 62% Sham; 34% gain 3 lines cf. 5% Sham)
Boyer, D.S., Antoszyk, A.N., Awh, C.C. et al. 2007. Subgroup Analysis of the MARINA Study of Ranibizumab in Neovascular Age-Related Macular Degeneration. Ophthalmology 114(2) 246-252.
Chang, T.S., Bressler, N.M., Fine, J.T. et al. 2007. Improved Vision-Related Function After Ranibizumab Treatment of Neovascular Age-Related Macular Degeneration: Results of a Randomized Clinical Trial. Archives of Ophthalmology 125(11) 1460-1469.
PrONTO [xx]
Neovascular AMD PRN treatment
PRN ranibizumab treatment satisfactory cf monthly
3 induction IVR doses, then monthly f/u & PRN dosing based on OCT
Reduces number of injections from 12 to 5 per year, while maintaining VA
Lalwani, G.A., Rosenfeld, P.J., Fung, A.E. et al. 2009. A variable-dosing regimen with intravitreal ranibizumab for neovascular age-related macular degeneration: year 2 of the PrONTO Study. Am J Ophthalmol 148(1) 43-58.e41.
PIER [xxi]
Neovascular AMD quarterly treatment
Monthly ranibizumab superior to quarterly injections
Abraham, P., Yue, H. and Wilson, L. 2010. Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER study year 2. Am J Ophthalmol 150(3) 315-324.e311.
SAILOR [xxii]
IVR Safety
No difference in rate of endophthalmitis and arterial thromboembolic events in 0.5 vs 0.3mg IVR group or frequency of injection use. Increased risk of stroke if prior history of stroke
Boyer, D.S., Heier, J.S., Brown, D.M. et al. 2009. A Phase IIIb study to evaluate the safety of ranibizumab in subjects with neovascular age-related macular degeneration. Ophthalmology 116(9) 1731-1739.
Larsen, M., Schmidt-Erfurth, U., Lanzetta, P. et al. 2012. Verteporfin plus ranibizumab for choroidal neovascularization in age-related macular degeneration: twelve-month MONT BLANC study results. Ophthalmology 119(5) 992-1000
Kaiser, P.K., Boyer, D.S., Cruess, A.F. et al. 2012. Verteporfin plus ranibizumab for choroidal neovascularization in age-related macular degeneration: twelve-month results of the DENALI study. Ophthalmology 119(5) 1001-1010.
CATT 1 AND 2 [xxv]
Comparison of Age-Related Macular Degeneration Treatments Trials
IVR equivalent to IVB
Monthly dosing superior to PRN
Monthly dosing showed more geographic atrophy
Martin DF, Maguire MG, Ying GS, Grunwald JE, Fine SL, Jaffe GJ. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med. 2011 May 19;364(20):1897-908. doi: 10.1056/NEJMoa1102673. Epub 2011 Apr 28. PMID: 21526923; PMCID: PMC3157322.
AREDS [xvvi]
Age-Related Eye Disease Study Category 3 – Extensive intermediate drusen, 1 large druse or noncentral geographic atrophy Category 4 – advanced AMD (central GA or wet AMD) in 1 eye only
Progression of AMD 5 years:
- Category 3: 20%
- Category 4: 40%
AREDS formulation: Beta-carotene, Vitamin C, Vitamin E, Zinc, Copper
25% risk reduction for development advanced AMD for categories 3 & 4
Group, A.-R.E.D.S.R. 2001. 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. Archives of Ophthalmology 119(10) 1417-1436.
AREDS2 [xvvii]
AREDS2 formulation: Lutein, Zeaxanthin, Vitamin C, Vitamin E, Zinc, Copper
Adding Omega 3 or lutein + zeaxanthin to AREDS → no additional benefit
Beta-carotene for smokers = more lung Ca
Replace AREDS beta-carotene with lutein + zeaxanthin → slightly better than AREDS alone
If deficient diet, lutein and zeaxanthin were more effective Reduced dose of Zinc → no change
Group*, T.A.-R.E.D.S.R. 2013. Lutein + Zeaxanthin and Omega-3 Fatty Acids for Age-Related Macular Degeneration: The Age-Related Eye Disease Study 2 (AREDS2) Randomized Clinical Trial. JAMA 309(19) 2005-2015.
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13.2 Cataract
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