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)

VIP [xv]

Treatment of occult AMD CNV with PDT

PDT reduces risk of vision loss by 40% for subfoveal purely occult CNV (cf. observation)

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

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.

MT BLANC [xxiii]

DENALI [xxiv]

Combination PDT + IVR

Mt. Blanc (Europe): PDT + IVR (PRN) non-inferior to IVR monotherapy (PRN) BUT no benefit in reducing the number of IVR retreatments over 12 months.

Denali (USA): PDT + IVR (PRN) not non-inferior to IVR monotherapy (PRN)

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

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


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