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Ursula Schmidt-Erfurth, Christopher Schuetze, Sebastian Waldstein, Bianca Gerendas, Christian Simader, Li Zhang, Michael Abramoff, Milan Sonka, Bernhard Baumann, Christoph Hitzenberger; Morphologic effects of anti-VEGF therapy on retinal pigment epithelium (RPE) and choroidal vasculature (CV) in neovascular age-related macular degeneration (AMD). Invest. Ophthalmol. Vis. Sci. 2013;54(15):6275.
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Intravitreal VEGF inhibition is the recommended first-line therapy in neovascular age-related macular degeneration (AMD). Recently, clinical evidence was noted of therapy-related adverse effects on retinal pigment epithelium (RPE) and choroidal vasculature (CV). In this prospective study, advanced imaging modalities were used to monitor RPE- and CV-related changes under continued anti-angiogenic therapy.
25 eyes with subfoveal neovascularization in AMD underwent standard ranibizumab treatment with a monthly regimen for 12 months, followed by PRN until month 24. RPE and CV layers were imaged at quarterly intervals during two years of follow-up. RPE alteration was determined by 3D polarization-sensitive optical coherence tomography (PS-OCT) with a resolution of 5 µm, a raster of 128x512 scans and an area of 6x6 mm. CV anatomy was reconstructed using a validated algorithm with Hessian analysis-based object detection followed by classic region-growing segmentation from spectral domain (SD)-OCT data (Zeiss Cirrus) and CV thickness was quantified by fitting a thin-plate spline of both sides.
Best-corrected visual acuity (BCVA) improved from 58 letters at baseline to 68 letters at 12 months and reached 57 letters at 24 months, while central retinal thickness (CRT) decreased from 453µm to 275µm and 325 µm, respectively. PS-OCT demonstrated persistent RPE integrity in 10 eyes, novel development of geographic atrophy (GA) in 14 eyes with 7 extrafoveal lesions. Progressive growth of GA with 0.25mm/0.51mm at 12/24 months was significant (p=0.01). Mean CV thickness in the central 6x6 mm area decreased from 143 µm at baseline to 138, 140 and 120 µm at month 3, 12 and 24, representing a progressive, but non-significant trend.
Continued anti-VEGF therapy of neovascular AMD appears to induce morphological changes at the level of RPE and choroid. RPE atrophy was progressive and significant, choroidal thinning was discrete, but detectable. Advanced imaging modalities are useful to identify and quantify disease- and treatment-related changes in a precise and reproducible manner, particularly since changes may be minor initially and progress slowly over time.
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