Showing papers by "Philip J. Rosenfeld published in 2012"

PERSPECTIVE Aflibercept for Age-Related Macular Degeneration: A Game-Changer or Quiet Addition?

Abstract: ● PURPOSE: To describe the pharmacokinetics, preclinical studies, and clinical trials of the newly approved anti–vascular endothelial growth factor (VEGF) drug aflibercept (Eylea (VEGF Trap-Eye); Regeneron; and Bayer). ● DESIGN: Review with editorial commentary. ● METHODS: A review of the medical literature and pertinent Internet postings combined with analysis of key studies with expert opinion regarding the use of aflibercept for the treatment of exudative age-related macular degeneration. ● RESULTS: Aflibercept, a fusion protein with binding domains from native VEGF receptors, binds VEGF-A, VEGF-B, and placental growth factors 1 and 2 with high affinity. Preclinical ophthalmologic studies demonstrated that aflibercept suppresses choroidal neovascularization in several animal models. The results of phase 1 and 2 trials showed excellent short-term suppression of choroidal neovascularization in patients with exudative agerelated macular degeneration and suggested a longer durability of aflibercept compared with other anti-VEGF drugs. The pivotal phase 3 Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration 1 and 2 trials showed that monthly and bimonthly aflibercept were noninferior to monthly ranibizumab at preventing vision loss (< 15-letter loss) with comparable vision gains and safety. Year 2 treatment involved monthly pro re nata injections with required injections every 3 months and maintained vision gains from the first year, with an average of 4.2 injections of aflibercept and 4.7 injections of ranibizumab. ● CONCLUSIONS: Aflibercept promises to deliver excellent visual outcomes for exudative age-related macular degeneration patients while undergoing fewer injections compared with ranibizumab. With a wholesale cost of $1850 per dose, the cost per patient with aflibercept

Automated detection of the foveal center improves SD-OCT measurements of central retinal thickness.

Abstract: BACKGROUND AND OBJECTIVE To investigate the performance of an automated foveal center detection algorithm on spectral-domain optical coherence tomography (SD-OCT). PATIENTS AND METHODS Fifty normal eyes and 50 eyes with early stage dry age-related macular degeneration (AMD) were analyzed. The actual scan center (SC), automatically detected foveal center (AF), and manually identified foveal center (MF) were compared. RESULTS The mean of the radial distances was 89 ± 120 μm from MF to SC and 54 ± 41 μm from MF to AF for normal eyes and 179 ± 125 μm from SC to MF and 104 ± 62 μm from AF to MF for eyes with AMD. The differences were statistically significant (P < .001). CONCLUSION The automated algorithm designed to detect the foveal center was more accurate in detecting the foveal center than relying on the fixation target of the SD-OCT instrument.

Review of Emerging Treatments for Age-Related Macular Degeneration

Abstract: In the era of pathway-based therapy, all treatments for AMD will address some step in the pathway that leads from early to late AMD. Steps in AMD pathogenesis that appear to be good targets for drug development include the following: (1) oxidative damage, (2) lipofuscin accumulation, (3) chronic inflammation, (4) mutations in the complement pathway, (5) mitochondrial damage, (6) Alu RNA accumulation in RPE, and (7) BMP-4 accumulation in RPE. Steps in neovascularization that can be targeted for drug development and combination therapy include the following: (1) angiogenic factor production, (2) extracellular factor release, (3) binding of factors to extracellular receptors (and activation of intracellular signaling after receptor binding), (4) endothelial cell activation (and basement membrane degradation), (5) endothelial cell proliferation, (6) directed endothelial cell migration, (7) extracellular matrix remodeling, (8) tube formation, and (9) vascular stabilization. Combination therapy will likely supplant monotherapy as the treatment of choice because the clinical benefits will likely be superior in preventing the complications of AMD.

Strategies for following dry age-related macular degeneration.

Abstract: Spectral domain optical coherence tomography (SDOCT) provides a novel strategy for imaging and monitoring progression in patients with age-related macular degeneration (AMD). The advantage of SDOCT over other imaging modalities or functional tests is that one modality can be used to image both drusen and geographic atrophy while obtaining reproducible, quantitative data on both drusen morphology and the area of geographic atrophy. Moreover, this strategy enables the clinician to follow the disease as it progresses from drusen to both geographic atrophy and choroidal neovascularization. No other imaging modality is able to quantitatively assess all forms of AMD. This unique feature of SDOCT makes it the ideal imaging modality for monitoring patients with AMD, providing routine care, and for following patients in clinical trials designed to assess the efficacy of new drugs for the treatment of dry AMD.

Management of Submacular Hemorrhage Secondary to Neovascular Age-Related Macular Degeneration with Anti-Vascular Endothelial Growth Factor Monotherapy

Abstract: � PURPOSE: To report the visual and anatomic outcomes of anti–vascular endothelial growth factor (VEGF) monotherapy in the management of marked submacular hemorrhage secondary to neovascular age-related macular degeneration (AMD). � DESIGN: Retrospective, interventional, consecutive case series. � METHODS: Nineteen eyes of 18patients with neovascular AMD and fovea involving submacular hemorrhage comprising greater than 50% of the lesion area were treated with anti-VEGF monotherapy. Main outcome measures included mean visual acuity change from baseline, mean central lesion thickness change from baseline, mean number of injections at 6 months, and adverse events.Snellenvisualacuitywasconvertedtoapproximate ETDRS letter score for the purpose of statistical analysis. � RESULTS: The mean change in approximate ETDRS letter score from baseline was D12 letters at 3 months (P [ .003), D18 letters at 6 months (P [ .001), andD17lettersat12monthsfollow-up(P[.02).Seven eyes received ranibizumab, 6 eyes received bevacizumab, and 6 eyes received both at various time points. The mean number of injections at 6 months was 4.7. The mean OCT central lesion thickness decreased from 755 mm to 349 mm at 6 months follow-up (P [ .0008).