Faculty Bibliography

Age-related macular degeneration (AMD) is the most frequent cause of irreversible blindness in the elderly in developed countries. Our previous studies implicated activation of complement in the formation of drusen, the hallmark lesion of AMD. Here, we show that factor H (HF1), the major inhibitor of the alternative complement pathway, accumulates within drusen and is synthesized by the retinal pigmented epithelium. Because previous linkage analyses identified chromosome 1q25-32, which harbors the factor H gene (HF1/CFH), as an AMD susceptibility locus, we analyzed HF1 for genetic variation in two independent cohorts comprised of approximately 900 AMD cases and 400 matched controls. We found association of eight common HF1 SNPs with AMD; two common missense variants exhibit highly significant associations (I62V, chi2 = 26.1 and P = 3.2 x 10(-7) and Y402H, chi2 = 54.4 and P = 1.6 x 10(-13)). Haplotype analysis reveals that multiple HF1 variants confer elevated or reduced risk of AMD. One common at-risk haplotype is present at a frequency of 50% in AMD cases and 29% in controls [odds ratio (OR) = 2.46, 95% confidence interval (1.95-3.11)]. Homozygotes for this haplotype account for 24% of cases and 8% of controls [OR = 3.51, 95% confidence interval (2.13-5.78)]. Several protective haplotypes are also identified (OR = 0.44-0.55), further implicating HF1 function in the pathogenetic mechanisms underlying AMD. We propose that genetic variation in a regulator of the alternative complement pathway, when combined with a triggering event, such as infection, underlie a major proportion of AMD in the human population

PURPOSE: To investigate the effect of photodynamic therapy (PDT) with verteporfin on patients with vitelliform lesions caused by cuticular drusen or adult-onset foveomacular vitelliform dystrophy (AOFVD). DESIGN: Observational case series. PATIENTS AND METHODS: Eight eyes of seven patients from two centers were examined prospectively. Each patient received PDT with verteporfin applied to the vitelliform lesions. RESULTS: Photodynamic therapy did not significantly affect the median visual acuity outcome (20/50 before PDT and 20/66 after PDT) in all seven treated patients. Of note, however, were four eyes of four patients who experienced a severe decrease in visual acuity after PDT with verteporfin. The temporary relationship of the vision loss to the treatment suggests that this may represent an adverse effect from therapy. The fluorescein angiographic appearance was virtually unchanged in all treated patients, whereas indocyanine green angiography showed typical PDT-associated reduction of choroidal perfusion in the treatment area. CONCLUSION: Photodynamic therapy does not have a positive influence on the visual outcome in patients with vitelliform lesions and may have a negative impact on vision in some treated patients. It is important for physicians using PDT to exercise caution in distinguishing between choroidal neovascular membranes and vitelliform lesions because the outcome in this latter group may be worse with application of PDT than with the natural course