Macular Degeneration: Zarbin MA

Zarbin MA. · No affiliation provided · Am J Ophthalmol. · Pubmed #17386276 No free full text.

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Zarbin MA. · No affiliation provided · Br J Ophthalmol. · Pubmed #16547308 links to  free full text

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Bhagat N, Grigorian RA, Tutela A, Zarbin MA. · The Institute of Ophthalmology and Visual Science, New Jersey Medical School, Newark, New Jersey, USA. · Surv Ophthalmol. · Pubmed #19171208 No free full text.

Abstract: Diabetic macular edema is a major cause of visual impairment. The pathogenesis of macular edema appears to be multifactorial. Laser photocoagulation is the standard of care for macular edema. However, there are cases that are not responsive to laser therapy. Several therapeutic options have been proposed for the treatment of this condition. In this review we discuss several factors and mechanisms implicated in the etiology of macular edema (vasoactive factors, biochemical pathways, anatomical abnormalities). It seems that combined pharmacologic and surgical therapy may be the best approach for the management of macular edema in diabetic patients.

Zarbin MA. · Institute of Ophthalmology and Visual Science at the New Jersey Medical School, University of Medicine and Dentistry of New Jersey, 90 Bergen Street, Suite 6100, Newark, NJ 07103-2499, USA. · Arch Ophthalmol. · Pubmed #15078679 No free full text.

Abstract: OBJECTIVE: To review and synthesize information concerning the pathogenesis of age-related macular degeneration (AMD). METHODS: Review of the English-language literature. RESULTS: Five concepts relevant to the cell biology of AMD are as follows: (1) AMD involves aging changes plus additional pathological changes (ie, AMD is not just an aging change); (2) in aging and AMD, oxidative stress causes retinal pigment epithelial (RPE) and, possibly, choriocapillaris injury; (3) in AMD (and perhaps in aging), RPE and, possibly, choriocapillaris injury results in a chronic inflammatory response within the Bruch membrane and the choroid; (4) in AMD, RPE and, possibly, choriocapillaris injury and inflammation lead to formation of an abnormal extracellular matrix (ECM), which causes altered diffusion of nutrients to the retina and RPE, possibly precipitating further RPE and retinal damage; and (5) the abnormal ECM results in altered RPE-choriocapillaris behavior leading ultimately to atrophy of the retina, RPE, and choriocapillaris and/or choroidal new vessel growth. In this sequence of events, both the environment and multiple genes can alter a patient's susceptibility to AMD. Implicit in this characterization of AMD pathogenesis is the concept that there is linear progression from one stage of the disease to the next. This assumption may be incorrect, and different biochemical pathways leading to geographic atrophy and/or choroidal new vessels may operate simultaneously. CONCLUSIONS: Better knowledge of AMD cell biology will lead to better treatments for AMD at all stages of the disease. Many unanswered questions regarding AMD pathogenesis remain. Multiple animal models and in vitro models of specific aspects of AMD are needed to make rapid progress in developing effective therapies for different stages of the disease.

Sugino IK, Wang H, Zarbin MA. · Institute of Ophthalmology and Visual Science, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 90 Bergen Street, Box 1709, Newark, NJ 07101-1709, USA. · Mol Neurobiol. · Pubmed #14576455 No free full text.

Abstract: Choroidal new vessel (CNV) excision may improve vision in patients with age-related macular degeneration (AMD) by eliminating the source of subretinal bleeding and scarring. Visual recovery after CNV excision is usually poor in AMD patients, probably because of removal of the associated retinal pigment epithelium (RPE), coupled with the inability of native RPE at the edge of the dissection bed to resurface the iatrogenic RPE defect. Experiments using in vitro and in vivo RPE wound-healing models have provided insight into the factors that regulate RPE wound healing in situ.Wound-healing studies using aged submacular human Bruch's membrane in organ culture show that resurfacing of localized RPE defects is influenced by the depth of damage to Bruch's membrane as well as factors that are intrinsic to the aged RPE at the wound edge. The Bruch's membrane organ-culture paradigm provides a surface for RPE wound healing that closely resembles the surface on which RPE must grow after CNV excision in AMD patients. An understanding of the factors that influence RPE wound healing might lead to treatments that stimulate RPE resurfacing and improve visual outcome after CNV excision.

Abdelsalam A, Del Priore L, Zarbin MA. · Department of Ophthalmology, New Jersey Medical School, Newark, USA. · Surv Ophthalmol. · Pubmed #10466585 No free full text.

Abstract: Drusen are subretinal pigment epithelial deposits that are characteristic of but not uniquely associated with age-related macular degeneration (AMD). Age-related macular degeneration is associated with two types of drusen that have different clinical appearances and different prognoses. Hard drusen appear as small, punctate, yellow nodules and can precede the development of atrophic AMD. Areolar atrophy of the retinal pigment epithelium (RPE), choriocapillaris, and outer retina develop as the drusen disappear, but drusen can regress without evidence of atrophy. Soft drusen appear as large (usually larger than 63 microm in diameter), pale yellow or grayish-white, dome-shaped elevations that can resemble localized serous RPE detachments. They tend to precede the development of clinically evident RPE detachments and choroidal neovascularization. Drusen characteristics correlated with progression to exudative maculopathy include drusen number (five or more), drusen size (larger than 63 microm in diameter), and confluence of drusen. Focal hyperpigmentation in the macula and systemic hypertension also are associated with an increased risk of developing choroidal new vessels (CNVs). Large drusen are usually a sign of diffuse thickening of Bruch's membrane with basal linear deposit, a vesicular material that probably arises from the RPE, constitutes a diffusion barrier to water-soluble constituents in the plasma, results in lipidization of Bruch's membrane, and creates a potential cleavage plane between the RPE basement membrane and the inner collagenous layer of Bruch's membrane through which CNVs can grow. Disappearance of drusen spontaneously and in areas adjacent to laser photocoagulation scars was first noted by Gass (Gass JD: Arch Ophthalmol 90:206-217, 1973; Trans Am Acad Ophthalmol Otolaryngol 75:580-608, 1971). Subsequent reports have confirmed these observations. Photocoagulation-induced drusen regression might prevent patients with drusen from developing exudative maculopathy. The mechanism for spontaneous drusen regression probably involves RPE atrophy. The mechanism for photocoagulation-induced drusen regression is unknown. If photocoagulation-induced drusen regression is anatomically similar to atrophy-associated drusen regression, then the former will be associated with dissolution of basal linear deposit and a residuum of basal laminar deposit. Sarks and coworkers (Sarks JP, Sarks SH, Killingsworth MC: Eye 11:515-522, 1997) proposed that this in turn will eliminate the potential cleavage plane between the RPE basement membrane and inner collagenous layer of Bruch's membrane through which CNVs grow, thus retarding the growth of CNVs.

Ruiz-Moreno JM, Montero JA, Barile S, Zarbin MA. · Department of Ophthalmology, Miguel Hernández University School of Medicine, Alicante, Spain. · Retina. · Pubmed #16829800 No free full text.

Abstract: PURPOSE: To evaluate the efficacy of photodynamic therapy with verteporfin (PDT) and high-dose intravitreous triamcinolone acetonide to treat choroidal new vessels (CNVs) associated with age-related macular degeneration (AMD). METHODS: In this prospective, consecutive, comparative, nonrandomized, interventional case series, 30 consecutive eyes of 30 patients with subfoveal CNVs associated with AMD were treated with PDT followed by the intravitreal injection of 19.4 +/- 2.1 mg /0.1 mL triamcinolone 5 days later. Fifteen eyes had received no previous treatment (group 1), and 15 had been treated previously with PDT alone (group 2). A group of 15 eyes of 15 patients treated with PDT alone, matched for age and CNV composition and size, served as controls. Changes in best-corrected visual acuity (BCVA; logMAR), the number of Snellen lines improved or lost, and the number of PDT sessions were considered as primary outcome indicators. RESULTS: Group 1 improved an average of 0.7 +/- 3.7 Snellen lines (range, -5 to 10) (P = 0.62), group 2 lost an average of -0.7 +/- 1.5 Snellen lines (range, -5 to 1) (P = 0.08), and the control group lost an average of -2.2 +/- 0.4 Snellen lines (range, -9 to 4) (P = 0.06; Wilcoxon signed rank test). The average number of PDT treatments during the 12-month follow-up was 1.6, 1.2, and 2.8 for group 1, group 2, and the control group, respectively. Intraocular pressure rose in 8 (57%) of 14 eyes in group 1 and in 7 (50%) of 14 eyes in group 2. Cataracts developed in 4 eyes (31%) in group 1 and in 4 eyes (33%) in group 2. CONCLUSION: Combined PDT/intravitreal triamcinolone acetonide as treatment for AMD-associated CNVs was associated with improved final BCVA and reduced the need for retreatment compared with historical controls.

Ruiz-Moreno JM, Montero JA, Zarbin MA. · Department of Ophthalmology, Miguel Hernández University School of Medicine, Alicante, Spain. · Retina. · Pubmed #17420698 No free full text.

Abstract: PURPOSE: To evaluate the efficacy of photodynamic therapy (PDT) and high-dose intravitreal triamcinolone acetonide (TA) injection to treat choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) at the 2-year follow-up. METHODS: In this prospective, consecutive, comparative, nonrandomized, interventional case series, 30 eyes of 30 consecutive patients with subfoveal CNV associated with AMD were treated by PDT followed by intravitreal injection of 19.4 +/- 2.1 mg TA. Fifteen eyes were naive to treatment (group 1), and 15 had been treated previously by PDT alone (group 2). A group of 15 eyes of 15 patients treated by PDT alone served as controls. The number of Snellen lines gained or lost and PDT sessions were evaluated. RESULTS: Best-corrected visual acuity (BCVA) did not change significantly in group 1 from baseline (0.0 +/- 3.4 Snellen line; range, -5 to 9 Snellen lines; P = 0.81); group 2 lost an average -0.6 +/- 2.5 line (range, -7 to 3 Snellen lines) (P = 0.41), and the control group lost an average of -2.2 +/- 3.4 lines (range, -8 to 2 Snellen lines) (P = 0.03, Wilcoxon signed rank test). The average number of PDT sessions during the 24-month follow-up was 1.9, 1.2, and 3.9 for group 1, group 2, and the control group, respectively. CONCLUSION: Two years after combined PDT/high-dose intravitreal TA to treat AMD-associated CNV, final BCVA was stable, and the need for retreatment was reduced compared with historical controls.

Duncan JL, Paskowitz DM, Nune GC, Yasumura D, Yang H, Matthes MT, Zarbin MA, LaVail MM. · University of California, San Francisco, California 94143, USA. · Adv Exp Med Biol. · Pubmed #17249587 No free full text.

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Gullapalli VK, Sugino IK, Van Patten Y, Shah S, Zarbin MA. · Institute of Ophthalmology and Visual Science, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey, USA. · Trans Am Ophthalmol Soc. · Pubmed #15747751 links to  free full text

Abstract: PURPOSE: To determine whether cultured fetal human retinal pigment epithelium (RPE) cells can attach and differentiate on submacular Bruch's membrane from donors over age 55. METHODS: Differential debridements of Bruch's membrane were performed to expose three different surfaces: the RPE basement membrane, the superficial inner collagenous layer (ICL) directly below the RPE basement membrane, and the deeper ICL. Approximately 3,146 cells/mm2 were seeded onto these Bruch's membrane explants and cultured for 1 or 7 days. Explants were bisected and examined histologically or analyzed with scanning electron microscopy. Nuclear density counts were performed on stained sections. Morphology and cell density were compared to those of cells seeded onto bovine corneal endothelial cell-extracellular matrix (BCE-ECM). RESULTS: Compared to cells seeded onto BCE-ECM at similar density, cell coverage and cellular morphology were poor at both time points. Unlike cells on BCE-ECM, cell density remained the same or decreased with time. In general, cell morphology on all surfaces worsened by day 7 compared to day 1. Although cells were more pigmented on RPE basement membrane and deep ICL at day 7, poor cellular morphology indicated the remaining cells were not well differentiated. An explant from a donor with large soft drusen showed the poorest resurfacing at day 7 in organ culture. CONCLUSIONS: These data indicate that aged submacular human Bruch's membrane does not support transplanted RPE survival and differentiation. The formation of localized RPE defects, cell death, and worsening cellular morphology on aged Bruch's membrane suggest that modification of Bruch's membrane may be necessary in patients with age-related macular degeneration receiving RPE transplants to prevent graft failure.

Gullapalli VK, Sugino IK, Van Patten Y, Shah S, Zarbin MA. · Institute of Ophthalmology and Visual Science, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ, USA. · Exp Eye Res. · Pubmed #15670802 No free full text.

Abstract: Resurfacing of diseased or iatrogenically damaged Bruch's membrane with healthy retinal pigment epithelium (RPE) has been proposed as adjunctive treatment for age-related macular degeneration (AMD). The purpose of this study was to determine whether cultured fetal human RPE cells can attach and differentiate on aged submacular human Bruch's membrane. Bruch's membrane was debrided to expose native RPE basement membrane, the superficial inner collagenous layer directly below the RPE basement membrane, or the deep inner collagenous layer. These are three surfaces that transplanted RPE cells will encounter in situ. Approximately 3146 cultured fetal RPE cells mm(-2) were seeded onto these three surfaces and grown in organ culture for 1, 7, or 14 days. Explants were bisected and examined histologically or analyzed with a scanning electron microscope. RPE nuclear density was measured on stained sections. Morphology and cell density were compared to cells seeded onto bovine corneal endothelial cell-extracellular matrix (BCE-ECM). In situ submacular RPE nuclear density was also measured in tissue sections of donor eyes ranging from 18 weeks gestation to 88 years of age to determine the effect of age on RPE density. Compared to cells seeded onto BCE-ECM at similar density, RPE cell coverage and cellular morphology on aged submacular human Bruch's membrane was poor at all time points. In contrast to cells on BCE-ECM, RPE cell density on Bruch's membrane decreased with time. In general, cell morphology on all three Bruch's membrane surfaces worsened by day-7 compared to day-1. Although some cells were more pigmented on RPE basement membrane and the deep inner collagenous layer at day-7, poor cellular morphology indicated the remaining cells were not well differentiated. At day-14, the cells were uniform and cuboidal on BCE-ECM, with cell density similar to that at day-7 and similar to in situ density of young donors (<age 30 years). The morphology of cells on Bruch's membrane was variable, and the nuclear density declined over time. A Bruch's membrane explant from a donor with large soft drusen showed the poorest resurfacing at day-7 in organ culture. These data indicate that aged submacular human Bruch's membrane does not support transplanted RPE survival and differentiation readily. The formation of localized RPE defects, cell death, and worsening cellular morphology on aged Bruch's membrane indicates that modification of Bruch's membrane may be necessary to prevent graft failure in AMD patients receiving RPE transplants.

Paskowitz DM, Nune G, Yasumura D, Yang H, Bhisitkul RB, Sharma S, Matthes MT, Zarbin MA, Lavail MM, Duncan JL. · Department of Ophthalmology, University of California, San Francisco, 94143-0730, USA. · Invest Ophthalmol Vis Sci. · Pubmed #15505074 links to  free full text

Abstract: PURPOSE: Verteporfin photodynamic therapy (PDT) is the most effective treatment for age-related macular degeneration, using laser activation of a photosensitizing dye to achieve closure of choroidal neovascularization. Although PDT preferentially affects pathologic vessels, it can also cause collateral damage to the overlying retina. In the current study, it was found that the neuroprotective agent brain-derived neurotrophic factor (BDNF) reduces this retinal damage. METHODS: Normal adult rats received intravitreal BDNF in one eye and PBS or no injection in the other eye 2 days before PDT. RESULTS: Control eyes exhibited choroidal hypofluorescence, moderate to severe photoreceptor loss, and depression of local retinal function measured using multifocal ERG in the laser-treated area. BDNF-injected eyes had more surviving photoreceptors and improved multifocal ERG responses 1 week after PDT. BDNF did not diminish the effect of PDT on the choroidal circulation as assessed by fluorescein angiography, and there was no evidence of retinal toxicity due to BDNF treatment. CONCLUSIONS: These results suggest that adjunctive neuroprotective therapy may reduce collateral damage to photoreceptors and improve visual outcome after PDT.

Wang H, Ninomiya Y, Sugino IK, Zarbin MA. · University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey 07103-2499, USA. · Invest Ophthalmol Vis Sci. · Pubmed #12714662 links to  free full text

Abstract: PURPOSE: To compare retinal pigment epithelium (RPE) resurfacing on the RPE basement membrane and inner collagenous layer (ICL) in human submacular Bruch's membrane explants. METHODS: Debridements were created in RPE-choroid-sclera explants (mean donor age 71.91 +/- 7.76 years) to create defects exposing the RPE basement membrane (RPEbm(+) defects), the ICL immediately below the RPE basement membrane (superficial ICL, [SICL]) or deeper layers of the ICL (DICL). Eleven pairs of eyes--four pairs with one eye having an RPEbm(+) defect and the fellow eye having an SICL defect and seven pairs with corresponding RPEbm(+) and DICL defects--were observed for 10 days by visualizing RPE ingrowth with 4',6'-diamino-2-phenylindole (DAPI) filters. At day 10, specimens were processed for scanning electron microscopy. RESULTS: Resurfacing of localized RPE defects occurred to some degree in all 11 pairs of eyes. No significant difference in the percentage of resurfacing of RPEbm(+) defects (67.35% +/- 18.82%) and SICL defects (64.26% +/- 16.07%) was observed although healing of the SICL showed more variability in the morphology of RPE cells migrating into the defect. Significant differences in healing were observed between pairs with RPEbm(+) defects versus DICL defects (84.07% +/- 15.35% and 54.00% +/- 14.54% resurfacing, respectively). RPE ingrowth into DICL defects exhibited the greatest morphologic variability. CONCLUSIONS: RPE basement membrane supports RPE resurfacing of localized RPE defects. The deeper portion of the ICL of aged submacular human Bruch's membrane does not support RPE resurfacing to the same extent as does the RPE basement membrane. The poor RPE resurfacing observed in DICL defects mimics the histopathological findings in patients with age-related macular degeneration after excision of choroidal new vessels.

Tsukahara I, Ninomiya S, Castellarin A, Yagi F, Sugino IK, Zarbin MA. · Department of Ophthalmology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, U.S.A. · Exp Eye Res. · Pubmed #11950236 No free full text.

Abstract: Retinal pigment epithelium (RPE) transplantation might replace cells lost as a consequence of choroidal neovascular membrane excision in patients with age-related macular degeneration (AMD). Autologous transplantation of RPE cells harvested from a peripheral biopsy may overcome problems of immune rejection. To study the feasibility of autologous RPE cell transplantation, the authors examined the attachment of freshly harvested RPE cells from aged donors onto Bruch's membrane explants, debrided to (1) remove or (2) preserve the RPE basement membrane. Human retinal pigment epithelial sheets were harvested from adult donor eyes (N = 12, mean age 79.00 +/- 9.40 years) and, following incubation in collagenase, were mechanically fragmented into microaggregates. Microaggregates (approximately 120 000 cells) were seeded onto the paired explants (7 mm diameter) and incubated for 20 min, 1, 4, or 24 hr at 37 degrees C. The percent coverage of the debrided surface by microaggregates was determined by sampling the center of the explants with scanning electron microscopy. RPE microaggregate attachment to Bruch's membrane was significantly greater at all time points analysed in samples with intact basement membrane versus those with an exposed inner collagenous layer. Coverage of debridements retaining intact RPE basement membrane was 1.83 +/- 1.10% at 20 min, 3.54 +/- 2.14% at 1 hr, and 8.68 +/- 2.63% at 4 hr. Coverage of debridements lacking basement membrane was 0.10 +/- 0.04% at 20 min, 0.39 +/- 0.25% at 1 hr, and 0.63 +/- 0.42% at 4 hr. Based on their morphologic appearance, many cells were dying as early as 1 hr following seeding. To increase surface coverage, the authors seeded four times the above number of cells and incubated the specimens for 1 hr. Coverage on explants lacking RPE basement membrane showed no increase in the number of cells attached to the inner collagenous layer. There was a significant approximately three-fold increase in the number of cells attached in the presence of basement membrane. These results indicate that if RPE cells from aged human donors are used for transplantation, some modification of the Bruch's membrane surface or the cells must be considered for cell attachment and eventual cell survival.

Fujii GY, De Juan E, Zarbin MA, Humayun MS, Au Eong KG, Phillips S. · Wilmer Ophthalmological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9277, USA. · Retina. · Pubmed #11508889 No free full text.

This publication has no abstract.

Bhagat N, Von Hagen S, Zarbin MA. · No affiliation provided · Am J Ophthalmol. · Pubmed #11860993 No free full text.

This publication has no abstract.