Managing the Patient with Bilateral Wet Macular Degeneration
Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents, ranibizumab (Lucentis, Genentech, South San Francisco, CA) and off-label intravitreal bevacizumab (Avastin, Genentech, South San Francisco, CA), are currently the most common agents used to treat wet age-related macular degeneration (AMD). Different treatment regimens have been employed in clinical trials utilizing ranibizumab including monthly injections (MARINA,1 ANCHOR2 trials) or less frequent treatments (PRONTO,3 SAILOR,4 PIER5 trials). In clinical practice, other paradigms used include injections according to need, and the "treat and extend" protocol.6 The clinical trials have shown the greatest visual recovery with monthly injections.
Simultaneous bilateral choroidal neovascularization (CNV) associated with AMD is a relatively common occurrence. In the Age-related Eye Disease Study, participants with advanced AMD in one eye or vision loss due to non-advanced AMD in one eye had a 43% expected probability of progression to advanced AMD in the fellow eye at five years.7 Bilateral wet AMD poses a dilemma for treatment as the treating physician attempts to balance the risk of delay in treatment with the risk of concurrent treatment. In addition, the burden of monthly injections must be considered when treating patients with bilateral wet AMD. Risks of bilateral treatment include risks of bilateral complications including endophthalmitis,8,9 inflammation,10 retinal detachment, corneal abrasions, and ocular irritation. If the burden of monthly injections to the patient and family becomes too great, the patient may become non-compliant with office visits and injections, and lose vision due to under-treatment. Current treatment strategies are being employed to attempt to combine the best possible outcome and least patient burden with the lowest risk.
New patients who present with simultaneous bilateral wet AMD can be treated with multiple regimens, as reported in the literature.11 One strategy is to perform bilateral simultaneous intravitreal injections of an anti-VEGF agent.12 A separate povidone-iodine prep, speculum, needle and syringe should be used for each eye.12 This is commonly practiced in the United States, and has been reported to be well-tolerated by patients.12 Many times newly diagnosed patients with bilateral wet AMD are not psychologically or physically prepared for simultaneous injections. In addition, initial therapy with bilateral injections does not allow assessment of patient tolerability and adverse effects to the medications. Therefore, for the first treatment session, it may be desirable to perform unilateral intravitreal injection of an anti-VEGF medication into one eye followed by contralateral intravitreal injection within the week. In addition to decreasing risk, it allows the patient time for psychological preparation as to the extent of his/her disease and required treatment. After the patient tolerates the initial injections, bilateral simultaneous injections may be desirable to patients as this allows less frequent trips to the physician.
Another option involves the use of combination therapy with photodynamic therapy (PDT) and intravitreal injection of medications including steroids and anti-VEGF agents.13, 14 Some studies have shown a potential ability to lengthen the time to needing retreatment.13, 14 One benefit of PDT treatment for bilateral exudative AMD is that simultaneous treatment utilizes a single intravenous injection of verteporfin. Our regimen is to perform reduced fluence PDT on both eyes on the day of the initial visit. Intravitreal injections can be performed in one eye on the same day as the PDT followed by injections into the contralateral eye several days later. Combination therapy may help delay patient visits and help ease the burden of monthly treatments.
Simultaneous bilateral CNV secondary to AMD is relatively common and provides a treatment dilemma. Several treatment approaches can be utilized to balance the benefit of early treatment with the risk of simultaneous bilateral treatments.
Rosenfeld PJ, Brown DM, Heier JS, et al.; MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006;355(14):1419-31.
Brown DM, Kaiser PK, Michels M, et al.; ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 2006;355(14):1432-44.
Rosenfeld PJ, Rich RM, Lalwani GA. Ranibizumab: Phase III clinical trial results. Ophthalmol Clin North Am. 2006;19(3):361-72.
Fung AE, Lalwani GA, Rosenfeld PJ, et al. An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration. Am J Ophthalmol 2007;143(4):566-83.
Regillo CD, Brown DM, Abraham P, et al. Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER Study year 1. Am J Ophthalmol 2008;145(2):239-248.
Spaide R. Ranibizumab according to need: a treatment for age-related macular degeneration. Am J Ophthalmol 2007;143(4):679-80
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;119:1417-1436
Fintak DR, Shah GK, Blinder KJ, et al. Incidence of endophthalmitis related to intravitreal injection of bevacizumab and ranibizumab. Retina 2008;28(10):1395-9.
Diago T, McCannel CA, Bakri SJ, et al. Infectious endophthalmitis after intravitreal injection of antiangiogenic agents. Retina. 2009 May;29(5):601-5.
Bakri SJ, Larson TA, Edwards AO. Intraocular inflammation following intravitreal injection of bevacizumab. Graefes Arch Clin Exp Ophthalmol. 2008 May;246(5):779-81.
Bakri SJ, Risco M, Edwards AO, Pulido JS. Bilateral Simultaneous Intravitreal Injections in the Office Setting. Am J Ophthalmol. 2009 Apr 27. [Epub ahead of print]
Fung AE, Palanki R, Bakri SJ, Depperschmidt E, Gibson A. Applying the CONSORT and STROBE statements to evaluate the reporting quality of neovascular age-related macular degeneration studies. Ophthalmology. 2009 Feb;116(2):286-96.
Augustin AJ, Puls S, Offermann I. Triple therapy for choroidal neovascularization due to age-related macular degeneration: verteporfin PDT, bevacizumab, and dexamethasone. Retina. 2007 Feb;27(2):133-40.
Bakri SJ, Couch SM, McCannel CA, Edwards AO. Same-day triple therapy with photodynamic therapy, intravitreal dexamethasone, and bevacizumab in wet age-related macular degeneration. Retina. 2009 May;29(5):573-8.
About our author(s):
Steve M. Couch, MD
Sophie J. Bakri, MD
Associate Professor of Ophthalmology
Vitreoretinal Diseases and Surgery