Effect of Early Detection of Neovascular AMD on Visual Outcome
Carl D. Regillo, MD
It certainly is logical to assume that early detection and treatment of neovascular AMD results in a better visual outcome. However, based on the way the pivotal clinical trials were designed in terms of analyzing outcomes, solid proof of this concept is lacking. There is, nevertheless, evidence to support the validity of our clinical impression that early intervention optimizes the ultimate visual outcome for our patients with neovascular AMD.
Going back to the photodynamic therapy trials with verteporfin, there was subgroup analysis from both the TAP and the VIP studies that suggest that smaller neovascular lesions of the occult and minimally classic type responded better to photodynamic therapy than larger lesions.1,2 In these trials, the proportion of eyes losing less than three lines of vision was higher with lesions that were less than four disc areas in size. Similarly, in the Macugen phase III VISION studies, there were trends in terms of the responder rates being higher in patients with small “early” lesions.3
With Lucentis, the jury is still out with regards to specific subgroup analyses that might help answer this question about better outcomes with early detection. What is known from the pivotal Lucentis trials is that the drug works well both in terms of stabilizing visual acuity over 12 to 24 months, and also improving vision.4,5 If there are similar rates of vision improvement regardless of the initial lesion size and acuity, it makes sense that when detecting the condition early when the visual acuity is still relatively good, the final visual acuity will likely be better compared to more advanced disease when the pretreatment visual acuity has already declined to a great degree.
In general, with all our therapies for AMD, what we are doing essentially is slowing or halting the progression of the disease and reducing or eliminating the exudative features. Whether this translates into visual stabilization or improvement, if the pretreatment visual acuity is relatively good, it seems likely that the final visual acuity will also be relatively better, and the limited available data support this impression.
We all look forward to further analyses of the clinical trial results to help support this impression.
1. Verteporfin Roundtable 2000 and 2001 Participants, Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP) Study Group Principal Investigators, and Verteporfin in Photodynamic Therapy (VIP) Study Group Principal Investigators. Guidelines for using verteporfin in photodynamic therapy to treat choroidal neovascularization due to age-related macular degeneration and other causes. Retina 2002;22:6-18.
2. Treatment of Age-related Macular Degeneration with Photodynamic Therapy and Verteporfin in Photodynamic Therapy Study Groups. Effect of lesion size, visual acuity, and lesion composition on visual acuity change with and without verteporfin therapy for choroidal neovascularization secondary to age-related macular degeneration: TAP and VIP report
no. 1. Am J Ophthalmol 2003;13:407-418.
3. The VEGF Inhibition Study in Ocular Neovascularization (V.I.S.I.O.N.) Clinical Trial Group. Enhanced efficacy associated with early treatment of neovacular age-related macular degeneration with pegaptanib sodium: An Exploratory Analysis Retina 2005;25:815-827.
4. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006;355:1419-1431.
5. Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 2006;355:1432-1444.