Macular Degeneration: Lewis GP

Wickham L, Lewis GP, Charteris DG, Fisher SK, Da Cruz L. · Vitreoretinal department, Moorfields Eye Hospital, City Road, London EC1V 2PD, UK. · Br J Ophthalmol. · Pubmed #19091855 No free full text.

Abstract: AIMS: To carry out a histopathological analysis of retinal specimens of patients undergoing translocation surgery for age-related macular degeneration (ARMD). METHODS: A histopathological analysis, using confocal microscopy, was performed on six retinal specimens. Results were compared with those from two further retinal specimens, collected during RPE transplantation, to control for the effects of vitrectomy and ARMD. In addition, a third control specimen from a cadaver with no history of ophthalmic disease was also analysed. RESULTS: In the translocation specimens, rods and cones were relatively well preserved but showed reduced density and outer segment length. In four specimens, there were focal areas of rod opsin redistribution to the inner segment, but this was not observed in the controls. Staining with calbindin was decreased in cones compared with controls but normal in horizontal and amacrine cells. Rod bipolar cells were mildly disorganised, and in one there was evidence of neurite sprouting. Glial fibrillar acidic protein was raised in both translocation and transplantation retinae but not in the cadaver control. CONCLUSIONS: In this study, there was little evidence of cellular injury following iatrogenic detachment; however, the rate of PVR following translocation surgery infers that cellular events set in motion may continue despite early reattachment.

Shahar J, Avery RL, Heilweil G, Barak A, Zemel E, Lewis GP, Johnson PT, Fisher SK, Perlman I, Loewenstein A. · Department of Ophthalmology, Tel-Aviv Medical Center, Israel. · Retina. · Pubmed #16508424 No free full text.

Abstract: PURPOSE: Intravitreal bevacizumab (Avastin; Genentech Inc., San Francisco, CA) is a new treatment for age-related macular degeneration. The aim of this study was to evaluate retinal penetration and toxicity of bevacizumab. METHODS: Ten albino rabbits were injected intravitreally with 0.1 mL (2.5 mg) of Avastin into one eye and 0.1 mL saline into the fellow eye. The electroretinogram (ERG) was recorded after 3 hours, 3 days, and 1, 2, and 4 weeks. The visual evoked potential (VEP) was recorded after 4 weeks. Confocal immunohistochemistry was used to assess retinal penetration. RESULTS: The ERG responses of the control and experimental eyes were similar in amplitude and pattern throughout the follow-up period. The flash VEP responses of the experimental eyes were of normal pattern and amplitude and did not differ from those recorded by stimulation of the control eye alone. Full thickness retinal penetration was present at 24 hours and was essentially absent at 4 weeks. CONCLUSIONS: Bevacizumab was found to be nontoxic to the retina of rabbits based on electrophysiologic studies. Full thickness retinal penetration may explain observed clinical effects of intravitreal bevacizumab. Although it is difficult to directly extrapolate to humans, our study supports the safe use of intravitreal bevacizumab injection.

Johnson PT, Lewis GP, Talaga KC, Brown MN, Kappel PJ, Fisher SK, Anderson DH, Johnson LV. · Neuroscience Research Institute, University of California, Santa Barbara, California 93106, USA. · Invest Ophthalmol Vis Sci. · Pubmed #14507896 links to  free full text

Abstract: PURPOSE. Drusen are variably sized extracellular deposits that form between the retinal pigmented epithelium (RPE) and Bruch's membrane. They are commonly found in aged eyes, however, numerous and/or confluent drusen are a significant risk factor for age-related macular degeneration. The purpose of this study was to investigate the impact of drusen on overlying cells of the retina. METHODS. Tissue containing retina and RPE/choroid was dissected from human donor eyes, embedded in agarose, and sectioned at 100 micro m using a vibratome. Sections were immunostained with a panel of antibodies that labeled glial cells, first-, second-, and third-order retinal neurons and processed for confocal microscopy. RESULTS. Retinal cells that overlie both soft and hard drusen exhibited numerous structural and molecular abnormalities. Normally detectable only in the outer segments of rod photoreceptors, rod opsin immunolabeling was also observed in the inner segment, cell body, axon, and axon terminal of photoreceptors that overlie drusen. Labeling with this antibody also revealed the deflection and shortening of rod inner and outer segments. Cone photoreceptors displayed similar structural abnormalities, as well as a decrease in cone opsin immunoreactivity. Drusen-associated abnormalities in the synaptic terminals of photoreceptor cells were also observed. In addition, an increase in intermediate filament protein immunoreactivity (vimentin and glial fibrillary acidic protein) was observed within Müller glial cells in areas of retina overlying drusen. Both soft and hard drusen were associated with a similar spectrum of effects in both macular and extramacular regions. Second- and third-order neurons, including bipolar, horizontal, amacrine, and ganglion cells all appeared unaffected. The structural and molecular abnormalities observed in photoreceptors and Müller glial cells were confined to retinal regions directly overlying and immediately adjacent to drusen; more distant retinal regions appeared unperturbed. Remarkably, significant abnormalities were observed over small subclinical drusen. CONCLUSIONS. Retinal cells overlying both soft and hard drusen exhibit structural and molecular abnormalities indicative of photoreceptor degeneration and Müller glial activation. These abnormalities resemble the degenerative effects common to many forms of retinal degeneration, but are confined to areas directly overlying drusen. This suggests that photoreceptor cell function is compromised as a consequence of drusen formation.