Macular Degeneration: Perlman I

Lang Y, Leibu R, Shoham N, Miller B, Perlman I. · Department of Ophthalmology, Ha'Emek Medical Center, Afula, Israel. · Ophthalmology. · Pubmed #17224183 No free full text.

Abstract: OBJECTIVE: To evaluate possible functional toxicity of intravitreal Kenalog (commercial triamcinolone acetonide) in patients' retinas. DESIGN: Observational case series. PARTICIPANTS: Thirty-two phakic eyes of 16 patients who had nonproliferative diabetic retinopathy and bilateral macular edema refractory to laser therapy, which had no other eye disorder and no previous ophthalmic operation. INTERVENTION: Kenalog (4 mg/0.1 ml) was injected intravitreally to one eye, whereas the second eye served as the control. The experimental eye was chosen as the eye with worse visual acuity (VA). MAIN OUTCOME MEASURES: Deterioration of electroretinogram parameters of the study eye measured at 3 months of follow-up when compared with the electroretinogram responses of the fellow, control eye and when compared with electroretinogram responses obtained before injection. Visual acuity, intraocular pressure (IOP), and eventual complications were assessed. No improvement or deterioration of VA or any increase in IOP was regarded as a secondary outcome. RESULTS: Average maximal response amplitude ratios of the dark-adapted b-wave (treated/control eyes) of the electroretinogram were 0.93 before (P = 0.221) and 0.94 (P = 0.387) 3 months after Kenalog injection. Average ratios of the light-adapted b-wave amplitude (treated/control eyes) of the electroretinogram were 1.04 (P = 0.702) before and 0.86 (P = 0.138) 3 months after Kenalog injection. No significant differences (P>0.05) were found between the electroretinogram parameters obtained from all eyes before and 3 months after Kenalog injection. Average VAs in the treated eyes were 1.08, 0.8, and 1.0 logarithm of the minimum angle of resolution units before and 2 and 4 months after injection, respectively. Temporary elevation of IOP was found in 4 treated eyes of 4 patients (25%). CONCLUSIONS: No electroretinographic evidence of a retinotoxic effect of intravitreal Kenalog was found in our patients.

Leibu R, Jermans A, Hatim G, Miller B, Sprecher E, Perlman I. · Department of Ophthalmology, Rambam Medical Center, Haifa, Israel. · Ophthalmology. · Pubmed #16650681 No free full text.

Abstract: PURPOSE: To evaluate retinal function in subjects suffering from hypotrichosis with juvenile macular dystrophy (HJMD). DESIGN: Retrospective case-control study. PARTICIPANTS: Sixteen HJMD patients belonging to 2 genetic groups and 20 control subjects. METHODS: The HJMD patients underwent clinical ophthalmological examination and electrophysiological testing for a period of as many as 14 years. The electroretinogram (ERG), electro-oculogram (EOG), and visual evoked potential (VEP) were recorded serially to assess visual function and to follow possible progression of the disease. MAIN OUTCOME MEASURES: Amplitudes and implicit times of ERG and VEP, and Arden ratio of EOG. RESULTS: Fundus examination revealed pigmentary abnormalities with atrophic changes at the posterior pole extending to regions beyond the macular area. A slow and time-dependent decline in visual acuity was noted. The ERG responses were subnormal in amplitude. The ERG deficit was similar for light- and dark-adapted responses. There was a gradual but consistent decrease in the ERGs with time. The EOG measurements were within the normal range. Pattern reversal VEPs were very subnormal, even in patients with mild deterioration of visual acuity. The flash VEPs were of slightly subnormal amplitudes and implicit times in the upper limit of the normal range. CONCLUSIONS: The fundus pictures and electrophysiological tests were consistent with retinal involvement extending beyond the macular region. Follow-up of visual acuity and ERG testing indicated a slowly progressing retinal disorder affecting cone-mediated vision as well as rod-mediated vision. Therefore, we suggest that a more appropriate name for this syndrome is hypotrichosis with cone-rod dystrophy.

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.

Sprecher E, Bergman R, Richard G, Lurie R, Shalev S, Petronius D, Shalata A, Anbinder Y, Leibu R, Perlman I, Cohen N, Szargel R. · Department of Dermatology, Rambam Medical Center, Haifa 31096, Israel. · Nat Genet. · Pubmed #11544476 No free full text.

Abstract: Congenital hypotrichosis associated with juvenile macular dystrophy (HJMD; MIM601553) is an autosomal recessive disorder of unknown etiology, characterized by hair loss heralding progressive macular degeneration and early blindness. We used homozygosity mapping in four consanguineous families to localize the gene defective in HJMD to 16q22.1. This region contains CDH3, encoding P-cadherin, which is expressed in the retinal pigment epithelium and hair follicles. Mutation analysis shows in all families a common homozygous deletion in exon 8 of CDH3. These results establish the molecular etiology of HJMD and implicate for the first time a cadherin molecule in the pathogenesis of a human hair and retinal disorder.

Perlman I, Segev E, Mazawi N, Merhav-Armon T, Lei B, Leibu R. · The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa. · Doc Ophthalmol. · Pubmed #11475365 No free full text.

Abstract: The visual evoked cortical potential (VECP) is widely used to verify complaints of reduced visual performance and to identify the site of the disorder. In this study, we investigated the correlation between reduced visual acuity and VECP in volunteers with normal corrected visual acuity and in patients suffering from inherited macular degeneration or from age related macular degeneration (ARMD). Flash evoked VECP was not affected by the visual acuity in the cases of refractive error and in ARMD patients but was reduced in amplitude and delayed in implicit time in the patients suffering from inherited macular degeneration. The VECP elicited by pattern reversal checkerboard (PVECP) was not affected by the quality of the visual image in volunteers with uncorrected refractive error when checks of 60' or larger were used but were considerably reduced in size and prolonged in implicit time for checks smaller than 15'. In both groups of patients suffering from macular dysfunction, pattern reversal VECP was very subnormal and was characterized by prolonged implicit time compared to values expected from their visual acuity. These findings indicate that the PVECP does not directly correlate with visual acuity but rather with foveal function. Therefore, we suggest that recordings of PVECP can be used to differentiate between refractive error and macular disorders as causing reduction in visual acuity when other clinical signs are missing or not available.