Macular Degeneration: Lu F

Lu F, Adelman RA. · Department of Ophthalmology and Visual Science, Yale University, School of Medicine, 40 Temple Street, Suite 3D, New Haven, CT 06510, USA. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #18781316 No free full text.

Abstract: BACKGROUND: Vascular endothelial growth factor (VEGF) is an important stimulator of choroidal neovascularization (CNV). Bevacizumab (Avastin), ranibizumab (Lucentis) and pegaptanib sodium (Macugen) are anti-VEGF medications that have been used in the treatment of CNV. The purpose of our study is to evaluate the efficacy and safety of intravitreal injections of bevacizumab, ranibizumab and pegaptanib sodium in the treatment of CNV in a rat model. METHODS: Multiple CNV lesions were induced by laser photocoagulation of the retina in Brown-Norway rats. After 3 weeks, 17 rats were divided into three groups and received intravitreal injections of bevacizumab, ranibizumab or pegaptanib sodium in different dosages. The lesions were evaluated by fluorescein angiography 1, 7, 14, and 28 days later to assess the efficacy of these medications. RESULTS: Different doses of bevacizumab did not show any effect on stopping the leakage on fluorescein angiography on days 1, 7, 14, and 28. Ranibizumab and pegaptanib sodium did not stop the leakage of CNV either. No angiographic or histopathologic toxicity was observed. CONCLUSIONS: These three anti-VEGF agents did not show any therapeutic effect on stopping CNV leakage in rats. Previous experiments with ranibizumab in monkeys resulted in a significant decrease in leakage of CNV. The difference may be due to the fact that both ranibizumab and bevacizumab are humanized and species-specific. There are several studies evaluating the effect of bevacizumab in non-primates. Since bevacizumab is humanized, the results of studies on non-primates may not be similar to humans and non-human primates.

Lu F, Hu J, Zhao P, Lin Y, Yang Y, Liu X, Fan Y, Chen B, Liao S, Du Q, Lei C, Cameron DJ, Zhang K, Yang Z. · Human Molecular Biology & Genetics, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Sichuan 610072, China. · Vision Res. · Pubmed #17904186 No free full text.

Abstract: Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment in the world. Advanced AMD can be divided into wet AMD (choroidal neovascularization) and dry AMD (geographic atrophy, GA). Drusen is characterized by deposits in the macula without visual loss and is an early AMD sign in the Caucasian population. rs11200638 in the promoter of HTRA1 has recently been shown to increases the risk for wet AMD in both Caucasian and Hong Kong Chinese populations. In order to replicate these results in a different cohort, we genotyped rs11200638 for 164 Chinese patients (90 wet AMD and 74 drusen) and 106 normal controls in a Han Mainland Chinese cohort. The genotypes were compared using chi square analysis for an additive allelic model. rs11200638 was significantly associated with wet AMD (p=5.00x10(-12)). Unlike in the Caucasian population, the risk allele of rs11200638 was not associated with drusen in our Chinese population. These findings confirm the association of HTRA1 with wet AMD.

Chen YX, Ge J, Yan M, Jin CJ, Zhang MX, Dong FT, Lu F, Zhang CF, Zhao JL. · Department of Ophthalmology, Peking Union Medical College Hospital, Eye Research Center of Chinese Academy of Medical Sciences, Beijing 100730, China. · Zhonghua Yan Ke Za Zhi. · Pubmed #17605900 No free full text.

Abstract: OBJECTIVE: To determine the safety and efficacy of verteporfin (visudyne) photodynamic therapy in age-related macular degeneration patients with subfoveal predominant choroidal neovascularization in China. METHODS: Multicenter, open-label, non-controlled clinical study. The included patients are diagnosed AMD patients with predominant classic CNV. The included patients received verteporfin intravenously followed by 689 nm laser light administration 15 minutes after the infusion start. The patients were be followed up for 24 weeks (+/-12 days) after initial verteporfin PDT treatment. Clinical follow-up was done at the end of week 12 (+/-12 days) and week 24 (+/-12 days) after the initial treatment. Additional treatment was given after 12 weeks from initial treatment if leakage from CNV was observed on fundus fluorescein angiogram. The visual acuity with ETDRS visual chart and the retinal lesion changes were documented and compared with baseline. The adverse events both in the process of treatment and in the follow-up were recorded throughout the entire study period. RESULTS: Thirty-one patients (31 eyes) were included and completed the trial with vertepofin PDT treatment. During the 24 weeks of the trial, 38.7% of the treated eyes had a vision gain more than 5 letters, 83.9% of the treated eyes had less than 15 letters vision loss. At week 12 after the initial treatment, 12.9% of the treated eyes had no leakage; 61.3% of the treated eyes had leakages, but limited to the former lesion, 25.8% of the treated eyes had increased leakage. The results at week 24 after the initial treatment were similar to those at week 12. At week 24 after the initial treatment, there were only slight enlargements in the lesion size, area of retinal lesion, the lesion surrounding area, and greatest linear dimension (GLD) of the lesion, but no statistical significant difference was found between baseline and week 12 after initial treatment (P = 0.65, 0.31, 0.12, respectively). No obvious progress of the fibrosis was detected in most of the PDT treated eyes. Eleven cases of adverse events (AE) occurred in our trial and the incidence was 34.4%. Among the 11 patients with reported adverse event, 7 (21.9%) had mild adverse event; 3 (9.4%) had moderate adverse events; 1 (3.1%) had a serious adverse event. During the study period, no abnormal changes were found in most of the laboratory tests including serum and urine biochemistry, hematology and Electrocadiogram. CONCLUSIONS: The results of this trial showed positive efficacy of PDT with verteporfin in the treatment of predominantly subfoveal CNV secondary to AMD by reducing the risk of vision loss. The incidence of serious adverse events was only 3.1%. It is highly safe to use PDT with verteporfin in Chinese AMD patients with subfoveal predominant classical CNV.