Macular Degeneration: Hughes MS

Shah GK, Sang DN, Hughes MS. · Barnes Retina Institute, Washington University School of Medicine, St. Louis, Missouri, USA. · Retina. · Pubmed #19202423 No free full text.

Abstract: BACKGROUND: Neovascular age-related macular degeneration is characterized by choroidal neovascularization that has a complex pathogenesis. Combining agents that have different mechanisms of action (i.e., verteporfin photodynamic therapy, antivascular endothelial growth factor, and/or anti-inflammatory therapies) could maximize clinical benefits through potential complementary effects. This review discusses findings from studies investigating this hypothesis. METHODS: Articles were retrieved from PubMed using relevant search terms. Abstracts from recent scientific meetings and details of ongoing trials from clinicaltrials.gov were also included. RESULTS: Following its approval, verteporfin was important in the management of choroidal neovascularization due to age-related macular degeneration for several years. Improved visual outcomes have now been reported with antiangiogenic agents (e.g., intravitreal ranibizumab), especially when frequently administered. Results from investigator-sponsored trials, retrospective case studies and Registries, which have provided insights into the latest findings from clinical practice in the "real-world" setting, as well as randomized controlled trials, suggest that a combination approach is generally well tolerated and may maintain improvements in visual and anatomic outcomes with fewer retreatments. CONCLUSION: A rationale exists for investigating combination approaches to target different processes in choroidal neovascularization pathogenesis, which may optimize treatment benefits in neovascular age-related macular degeneration. Encouraging data suggest that combination strategies are not associated with major adverse events.

Kaiser PK, Anonymous00056, Boyer DS, Garcia R, Hao Y, Hughes MS, Jabbour NM, Kaiser PK, Mieler W, Slakter JS, Samuel M, Tolentino MJ, Roth D, Sheidow T, Strong HA. · Cole Eye Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. · Ophthalmology. · Pubmed #19243834 No free full text.

Abstract: PURPOSE: To assess outcomes for patients with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) treated with verteporfin photodynamic therapy (PDT) and bevacizumab. DESIGN: Retrospective, case series database study (registry). PARTICIPANTS: We included 1196 patients with CNV due to AMD who received > or =1 combination treatment of 1.25 mg intravitreal bevacizumab within 14 days of verteporfin PDT. METHODS: Retrospective analysis of baseline data with ongoing follow-up. Physicians from 45 clinical centers entered patient data at baseline and follow-up examinations, including subsequent treatments, into a secure, Web-accessed database. Snellen visual acuity (VA) was converted to logarithm of the minimum angle of resolution (logMAR) for statistical analyses. MAIN OUTCOME MEASURES: Change from baseline in VA and retreatment rates of any therapy after the initial combination treatment. RESULTS: Of 1196 patients, 1073 patients had > or =6 months of follow-up. For these 1073 patients, mean baseline VA was 0.967 logMAR (approximate Snellen 20/185) and 56.3% of patients (604/1073) were treatment naïve. After their baseline combination treatment, patients received a mean of 0.6 additional verteporfin PDT retreatments and 2.0 bevacizumab retreatments over a mean follow-up period of 15.0 months. By 12 months, 82% of patients (578/701) had stable or improved vision (loss of <3 lines or a gain in VA), 36% (255/701) improved by > or =3 lines, and 17% (121/701) improved by > or =6 lines. By 12 months, patients gained approximately 1.2 lines (6 letters) of VA from baseline. Patients who were treatment naïve gained significantly more VA by month 12 (+8.4 letters) compared with those who had been previously treated (+2.4 letters; P<0.01). Most serious adverse events (26/30) were judged by investigators as not related to any study treatment, although 3 ocular events were judged related to bevacizumab alone, and 1 ocular event was judged related to both bevacizumab and PDT. CONCLUSIONS: Combination therapy with PDT and bevacizumab led to vision benefit for most patients, particularly those who were treatment naïve at baseline. The number of retreatments was lower than published reports with either treatment delivered as monotherapy. Randomized clinical trials are underway to confirm these findings.

Hughes MS, Sang DN. · Schepens Eye Research Institute and the Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA. · Ophthalmic Surg Lasers Imaging. · Pubmed #17152537 No free full text.

Abstract: BACKGROUND AND OBJECTIVE: Vascular endothelial growth factor (VEGF)-A, both necessary and sufficient in promoting ocular neovascularization, is an attractive therapeutic target. Combining nonselective and selective VEGF blockade may provide clinical benefit with minimal risks in the treatment of neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: Twenty patients with all subtypes of neovascular AMD and a broad range of baseline vision were treated with intravitreal bevacizumab followed by pegaptanib sodium for 54 weeks. Visual acuity measurements, biomicroscopy, funduscopy, fluorescein angiography, optical coherence tomography, and adverse event assessments were performed. RESULTS: Mean visual acuity improved from approximately 20/200 at baseline to 20/80. All patients experienced an improvement in retinal thickness, ranging from -47 to -297 microns. Adverse events were limited to transient irritation or redness. No significant elevation in intraocular pressure occurred following either bevacizumab or pegaptanib injections. CONCLUSIONS: Nonselective VEGF blockade with bevacizumab induction and selective VEGF165 blockade with pegaptanib as maintenance therapies may offer clinically meaningful outcomes with acceptable safety profiles in patients with AMD.