Macular Degeneration: Sternberg P

Bressler NM, Hawkins BS, Sternberg P, McDonald HR, Steinberg P. · No affiliation provided · Ophthalmology. · Pubmed #11237895 No free full text.

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Sternberg P, Lewis H. · Department of Ophthalmology and Visual Sciences (P.S.), Vanderbilt University Medical Center, Nashville, Tennessee, USA. · Am J Ophthalmol. · Pubmed #15013872 No free full text.

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Cai J, Nelson KC, Wu M, Sternberg P, Jones DP. · Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA. · Prog Retin Eye Res. · Pubmed #10674708 No free full text.

Abstract: This review provides a model for the role of oxidative stress in the etiology of age-related macular degeneration (AMD). Epidemiological studies of diet, environmental and behavioral risk factors suggest that oxidative stress is a contributing factor of AMD. Pathological studies indicate that damage to the retinal pigment epithelium (RPE) is an early event in AMD. In vitro studies show that oxidant treated RPE cells undergo apoptosis, a possible mechanism by which RPE cells are lost during early phase of AMD. The main target of oxidative injury seems to be mitochondria, an organelle known to accumulate genomic damages in other postmitotic tissues during aging. The thiol antioxidant GSH and its amino acid precursors protect RPE cells from oxidant-induced apoptosis. Similar protection occurs with dietary enzyme inducers which increase GSH synthesis. These results indicate that therapeutic or nutritional intervention to enhance the GSH antioxidant capacity of RPE may provide an effective way to prevent or treat AMD.

Winkler BS, Boulton ME, Gottsch JD, Sternberg P. · Eye Research Institute, Oakland University, Rochester, MI 48309, USA. · Mol Vis. · Pubmed #10562656 links to  free full text

Abstract: This article provides current information on the potential role of oxidation in relation to age-related macular degeneration (AMD). The emphasis is placed on the generation of oxidants and free radicals and the protective effects of antioxidants in the outer retina, with specific emphasis on the photoreceptor cells, the retinal pigment epithelium and the choriocapillaris. The starting points include a discussion and a definition of what radicals are, their endogenous sources, how they react, and what damage they may cause. The photoreceptor/pigment epithelium complex is exposed to sunlight, is bathed in a near-arterial level of oxygen, and membranes in this complex contain high concentrations of polyunsaturated fatty acids, all considered to be potential factors leading to oxidative damage. Actions of antioxidants such as glutathione, vitamin C, superoxide dismutase, catalase, vitamin E and the carotenoids are discussed in terms of their mechanisms of preventing oxidative damage. The phototoxicity of lipofuscin, a group of complex autofluorescent lipid/protein aggregates that accumulate in the retinal pigment epithelium, is described and evidence is presented suggesting that intracellular lipofuscin is toxic to these cells, thus supporting a role for lipofuscin in aging and AMD. The theory that AMD is primarily due to a photosensitizing injury to the choriocapillaris is evaluated. Results are presented showing that when protoporphyric mice are exposed to blue light there is an induction in the synthesis of Type IV collagen synthesis by the choriocapillary endothelium, which leads to a thickened Bruch's membrane and to the appearance of sub-retinal pigment epithelial fibrillogranular deposits, which are similar to basal laminar deposits. The hypothesis that AMD may result from oxidative injury to the retinal pigment epithelium is further evaluated in experiments designed to test the protective effects of glutathione in preventing damage to cultured human pigment epithelial cells exposed to an oxidant. Experiments designed to increase the concentration of glutathione in pigment epithelial cells using dimethylfumarate, a monofunctional inducer, are described in relation to the ability of these cells to survive an oxidative challenge. While all these models provide undisputed evidence of oxidative damage to the retinal pigment epithelium and the choriocapillaris that is both light- and oxygen-dependent, it nevertheless is still unclear at this time what the precise linkage is between oxidation-induced events and the onset and progression of AMD.

Bressler NM, Bressler SB, Childs AL, Haller JA, Hawkins BS, Lewis H, MacCumber MW, Marsh MJ, Redford M, Sternberg P, Thomas MA, Williams GA, Anonymous00091. · SST Coordinating Center, Wilmer Clinical Trials and Biometry, 550 North Broadway, 9th Floor, Baltimore, MD 21205-2010, USA. · Ophthalmology. · Pubmed #15522364 links to  free full text

Abstract: PURPOSE: To present best-corrected visual acuity (BCVA) findings and other clinical outcomes from eyes of patients enrolled in one of the Submacular Surgery Trials (SST) evaluating surgical removal versus observation of predominantly hemorrhagic subfoveal choroidal neovascularization (CNV) associated with age-related macular degeneration. DESIGN: Randomized clinical trial (SST Group B Trial). PARTICIPANTS: Eligible patients had subfoveal choroidal neovascular lesions greater than 3.5 disk areas (8.9 mm2) composed of at least 50% blood (either blood or CNV underlying the center of the foveal avascular zone) and BCVA of 20/100 to light perception in the study eye. INTERVENTION: Patients were assigned randomly at time of enrollment to observation or surgical removal of blood and any associated CNV. MAIN OUTCOME MEASURE: A successful outcome was defined a priori as either improvement in visual acuity (VA), no change in VA, or a decline in VA of no more than 1 line (7 letters) from baseline to the 24-month examination based on an intent-to-treat analysis. RESULTS: Of 336 patients enrolled, 168 were assigned to each treatment arm; treatment arms were balanced by baseline characteristics. Of 1501 expected examinations 3 months through 36 months after baseline, 1370 (91%) were performed. Loss of > or =2 lines (> or =8 letters) of VA occurred in 56% of surgery eyes, versus 59% of observation eyes examined at 24 months. Although severe loss of VA was not the primary outcome of interest, surgery more often prevented such loss: 36% in the observation arm versus 21% in the surgery arm at the 24-month examination (chi2 P = 0.004). Of initially phakic eyes, the cumulative percentage that had undergone cataract surgery by 24 months was 44% in the surgery arm, compared with 6% in the observation arm. Twenty-seven eyes (16%) in the surgical arm, compared with 3 eyes (2%) in the observation arm, had a rhegmatogenous retinal detachment (RD). CONCLUSIONS: Submacular surgery as performed in the SST Group B Trial did not increase the chance of stable or improved VA (the primary outcome of interest) and was associated with a high risk of rhegmatogenous RD, but did reduce the risk of severe VA loss in comparison with observation. This article contains additional online-only material available at http://www.ophsource.com/periodicals/ophtha.

Hawkins BS, Bressler NM, Miskala PH, Bressler SB, Holekamp NM, Marsh MJ, Redford M, Schwartz SD, Sternberg P, Thomas MA, Wilson DJ, Anonymous00089. · SST Coordinating Center, Wilmer Clinical Trials and Biometry, 550 North Broadway, 9th Floor, Baltimore, MD 21205-2010, USA. · Ophthalmology. · Pubmed #15522362 links to  free full text

Abstract: PURPOSE: To present visual acuity (VA) and related findings from patients enrolled in one of the Submacular Surgery Trials (SST) evaluating surgical removal versus observation of subfoveal choroidal neovascularization secondary to age-related macular degeneration (SST Group N Trial). DESIGN: Randomized clinical trial. PARTICIPANTS: Eligible patients had age-related macular degeneration with subfoveal choroidal neovascularization, some with a classic pattern on fluorescein angiography, and best-corrected VA (BCVA) of 20/100 to 20/800 in one eye (study eye) that had received no treatment in the macula. Any contiguous blood had to account for <50% of the total area occupied by the subfoveal lesion (maximum size, 9.0 disc areas [22.9 mm2]). METHODS: Randomization was stratified by VA and by clinical center. All patients were scheduled for study examinations at 3, 6, 12, and 24 months after enrollment for assessment of study outcomes. MAIN OUTCOME MEASURE: A successful outcome was defined a priori to be either improvement of BCVA or VA no more than 1 line (7 letters) worse than baseline at the 24-month examination. RESULTS: Of 454 patients enrolled, 228 study eyes were assigned to observation and 226 to surgery. The percentages of eyes that had successful outcomes were similar in the 2 arms: 44% assigned to observation and 41% assigned to surgery. Median VA losses from baseline to the 24-month examination were 2.1 lines (10.5 letters) in the observation arm and 2.0 lines (10 letters) in the surgery arm. Median VA declined from 20/100 at baseline to 20/400 at 24 months in both arms. No subgroup of patients was identified in which submacular surgery led to better VA outcomes. In the surgery arm, 55 (39%) of 142 initially phakic eyes had cataract surgery by the 24-month examination, compared with 6 (5%) of 133 eyes in the observation arm. Rhegmatogenous retinal detachment occurred in 12 surgery eyes (5%) and 1 observation eye. CONCLUSIONS: Submacular surgery, as performed in this clinical trial, did not improve or preserve VA for 24 months in more eyes than observation and is not recommended for patients with similar lesions. This article contains additional online-only material available at http://www.ophsource.com/periodicals/ophtha.

Bressler NM, Bressler SB, Hawkins BS, Marsh MJ, Sternberg P, Thomas MA, Anonymous00036. · No affiliation provided · Am J Ophthalmol. · Pubmed #11024412 No free full text.

Abstract: PURPOSE: To report complications and changes in vision during 2 years of follow-up of patients with age-related macular degeneration assigned randomly to surgical removal or to laser photocoagulation of subfoveal recurrent neovascular lesions in a pilot trial designed to test methods, to refine estimates of outcome rates, and to project patient accrual rates for a larger multicenter randomized trial to evaluate submacular surgery. PATIENTS AND METHODS: Eligible patients with previous laser photocoagulation of extrafoveal or juxtafoveal choroidal neovascularization secondary to age-related macular degeneration were enrolled at 15 collaborating clinical centers. Assignments to treatment arm were made by personnel at a central coordinating center. Adherence to eligibility criteria and treatment assignment was assessed centrally at a photograph reading center. Patients were examined at 3, 6, 12, and 24 months after treatment for data collection purposes. Outcome measures reported include treatment complications, adverse events, requirements for additional treatment, and 2-year changes in visual acuity from baseline. RESULTS: Of 70 patients enrolled, 36 were assigned to laser photocoagulation and 34 to submacular surgery; all were treated as assigned. One patient in each group died before the 2-year examination. Visual acuity was measured at the 2-year examination for 31 of the surviving patients (89%) in the laser arm and for 28 of the surviving patients (85%) in the surgery arm. The 2-year measurements for 36 of the 59 patients (61%) were made by an examiner masked to treatment assignment and to the identity of the study eye. Improvements and losses of visual acuity were observed in both treatment arms; 20 of 31 study eyes (65%) in the laser arm and 14 of 28 study eyes (50%) in the surgery arm had visual acuity 2 years after enrollment that was better than or no more than 1 line worse than the baseline level. Changes in visual acuity and the size of the central macular lesions from baseline to the 2-year examination were similar in the treatment arms. Few serious complications were observed in either arm at the time of initial treatment; serious adverse events were rare. During follow-up, 11 laser-treated eyes and 18 surgically treated eyes had additional intraocular procedures. CONCLUSIONS: The data from this pilot trial suggest no reason to prefer submacular surgery over laser photocoagulation for treatment of patients with age-related macular degeneration who have lesions similar to those studied in this pilot trial. Any clinical trial designed to compare submacular surgery with laser photocoagulation in eyes with age-related macular degeneration and subfoveal recurrent neovascular lesions must enroll several hundred patients in order to reach a statistically valid conclusion regarding differences between these two methods of treatment with respect to either changes in visual acuity or complication rates.

Canter JA, Olson LM, Spencer K, Schnetz-Boutaud N, Anderson B, Hauser MA, Schmidt S, Postel EA, Agarwal A, Pericak-Vance MA, Sternberg P, Haines JL. · Center for Human Genetics Research, Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America. · PLoS One. · Pubmed #18461138 links to  free full text

Abstract: The objective of this study was to determine if MTND2*LHON4917G (4917G), a specific non-synonymous polymorphism in the mitochondrial genome previously associated with neurodegenerative phenotypes, is associated with increased risk for age-related macular degeneration (AMD). A preliminary study of 393 individuals (293 cases and 100 controls) ascertained at Vanderbilt revealed an increased occurrence of 4917G in cases compared to controls (15.4% vs.9.0%, p = 0.11). Since there was a significant age difference between cases and controls in this initial analysis, we extended the study by selecting Caucasian pairs matched at the exact age at examination. From the 1547 individuals in the Vanderbilt/Duke AMD population association study (including 157 in the preliminary study), we were able to match 560 (280 cases and 280 unaffected) on exact age at examination. This study population was genotyped for 4917G plus specific AMD-associated nuclear genome polymorphisms in CFH, LOC387715 and ApoE. Following adjustment for the listed nuclear genome polymorphisms, 4917G independently predicts the presence of AMD (OR = 2.16, 95%CI 1.20-3.91, p = 0.01). In conclusion, a specific mitochondrial polymorphism previously implicated in other neurodegenerative phenotypes (4917G) appears to convey risk for AMD independent of recently discovered nuclear DNA polymorphisms.

Jiang S, Moriarty-Craige SE, Li C, Lynn MJ, Cai J, Jones DP, Sternberg P. · Department of Medicine, Emory University School of Medicine, Emory University, Atlanta, Georgia, USA. · Invest Ophthalmol Vis Sci. · Pubmed #18385048 links to  free full text

Abstract: PURPOSE: To evaluate the associations between plasma-soluble Fas ligand (sFasL) and age-related macular degeneration (AMD). METHODS: Plasma samples were obtained from 230 individuals (age range, 45-85), with or without AMD. The concentrations of sFasL were determined by an enzyme-linked immunosorbent assay (ELISA). The measured sFasL levels were transformed into cubic roots and were fitted into linear regression models against AMD status, with adjustment for age and sex. RESULTS: Plasma sFasL increased with age and AMD. There was a linear correlation between age and the cubic roots of sFasL. The plasma sFasL concentrations in non-AMD subjects ranged from 0 to 1.63 ng/mL (median, 0.69 ng/mL), whereas in patients with AMD, sFasL ranged from 0 to 2.43 ng/mL (median, 0.18 ng/mL). Between the ages of 61 and 84, the subjects with AMD had significantly higher sFasL than did the non-AMD subjects. There was a sexual dimorphism of the plasma sFasL levels. In non-AMD subjects, sFasL was lower in the females. In patients with AMD, sFasL was higher in the females. CONCLUSIONS: An elevation of plasma sFasL with aging may play a role in the development of AMD and is a potential peripheral marker for monitoring disease progression.

Moriarty-Craige SE, Ha KN, Sternberg P, Lynn M, Bressler S, Gensler G, Jones DP. · Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. · Am J Ophthalmol. · Pubmed #17157802 links to  free full text

Abstract: PURPOSE: To determine the effects of zinc supplementation on plasma thiol metabolites and their redox status in a cohort of patients with age-related macular degeneration (AMD). DESIGN: Randomized clinical trial that evaluated the effects of high doses of zinc and antioxidants on plasma biomarkers of oxidative stress. METHODS: This was an ancillary study of the Age-Related Eye Disease Study (AREDS). Subjects with AMD were randomized to one of four treatment groups: (1) antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg), (2) zinc (80 mg zinc oxide, 2 mg cupric oxide), (3) antioxidants plus zinc, or (4) placebo. At 20 and 80 months after randomization, blood specimens were collected and analyzed for glutathione (GSH), oxidized glutathione (GSSG), cysteine (Cys), and cystine (CySS). RESULTS: Although zinc supplementation had no apparent effect on plasma thiol/disulfide redox status at the first blood draw, the group of patients receiving zinc supplementation at the second blood draw had significantly less CySS compared with those not receiving zinc (54.9 vs 64.1 microM; P = .01). There was a time-dependent oxidation of the plasma GHS pool and was not affected by zinc supplementation. CONCLUSIONS: Because increased CySS level is associated with aging, oxidative stress, and age-related diseases, the apparent prevention of increased CySS by zinc supplementation warrants additional investigation.

Hudson HL, Lane SS, Heier JS, Stulting RD, Singerman L, Lichter PR, Sternberg P, Chang DF, Anonymous00087. · Retina Centers, Tucson, Arizona, USA. · Ophthalmology. · Pubmed #16989902 No free full text.

Abstract: PURPOSE: To evaluate the safety and efficacy of an implantable visual prosthetic device (IMT; VisionCare Ophthalmic Technologies, Saratoga, CA) in patients with bilateral, end-stage age-related macular degeneration (AMD). DESIGN: Prospective, open-label, multicenter clinical trial with fellow eye controls. PARTICIPANTS: A total of 217 patients (mean age, 76 years) with AMD and moderate to profound bilateral central visual acuity loss (20/80-20/800) resulting from bilateral untreatable geographic atrophy, disciform scars, or both were enrolled. METHODS: A visual prosthetic device (implantable telescope), designed to enlarge retinal images of the central visual field, was implanted monocularly in the capsular bag after lens extraction. Fellow eyes were not implanted to provide peripheral vision and served as controls. Study patients participated in 6 visual rehabilitation visits after surgery. MAIN OUTCOME MEASURES: Best-corrected distance visual acuity (BCDVA) and best-corrected near visual acuity (BCNVA), quality-of-life scores from the National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) and the Activities of Daily Life scale, endothelial cell density (ECD), and incidence of complications and adverse events. RESULTS: At 1 year, 67% of implanted eyes achieved a 3-line or more improvement in BCDVA versus 13% of fellow eye controls (P<0.0001). Fifty-three percent of implanted eyes achieved a 3-line or more improvement in both BCDVA and BCNVA versus 10% of fellow eyes (P<0.0001). Mean BCDVA and BCNVA improved 3.5 lines and 3.2 lines, respectively, in implanted eyes versus 0.8 lines and 1.8 lines, respectively, in fellow eyes (P<0.0001). Change in visual acuity was not related to lesion type. Mean NEI VFQ-25 scores improved by more than 7 points from baseline (P<0.01) on 7 of 8 relevant subscales. Eleven eyes did not receive the device because of an aborted procedure. Endothelial cell density was reduced by 20% at 3 months and 25% at 1 year. The decrease in ECD was correlated with postsurgical edema (P<0.0001), and there was no evidence that endothelial cell loss is accelerated by ongoing endothelial trauma after implantation. CONCLUSIONS: This implantable visual prosthesis can improve visual acuity and quality of life in patients with moderate to profound visual impairment caused by bilateral, end-stage AMD.

Ha KN, Chen Y, Cai J, Sternberg P. · Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-8808, USA. · Invest Ophthalmol Vis Sci. · Pubmed #16723490 links to  free full text

Abstract: PURPOSE: To determine the molecular mechanisms underlying the protective effects of zinc against oxidative stress in cultured retinal pigment epithelial (RPE) cells. METHODS: Cultured ARPE-19 cells were treated with different concentrations of zinc for various times. Cellular glutathione (GSH) and glutathione disulfide (GSSG) levels were measured by high-performance liquid chromatography (HPLC). Glutamate-cysteine ligase (GCL) expression was measured by quantitative reverse transcription-PCR (RT-PCR). Nuclear factor erythroid2-related factor (Nrf2) activity was measured in a dual luciferase assay after transfection of reporter plasmids containing the antioxidant response element (ARE). The small interference (si)RNA approach was used to knock down the expression of Nrf2. RESULTS: Zinc significantly increased GSH levels in ARPE-19 cells through induction of the de novo synthesis pathway. At 150 microM, zinc increased the GSH level by 70%. At similar concentrations, zinc upregulated the mRNA level of GCL and activated the ARE-Nrf2 pathway. The effects of zinc on ARE activation and GSH synthesis were inhibited by knockdown of Nrf2 expression using the siRNA approach. CONCLUSIONS: Induction of the ARE-Nrf2 pathway by zinc provides powerful and prolonged antioxidation and detoxification that may explain the beneficial effects of zinc observed in the treatment of age-related macular degeneration (AMD).

Moriarty-Craige SE, Adkison J, Lynn M, Gensler G, Bressler S, Jones DP, Sternberg P. · Department of Ophthalmology, Biochemistry, and Medicine, Emory University, Atlanta, Georgia, USA. · Am J Ophthalmol. · Pubmed #16376645 No free full text.

Abstract: PURPOSE: Determine whether antioxidant supplements alter the plasma glutathione and/or cysteine redox potential in age-related macular degeneration (AMD) patients. DESIGN: This was an ancillary study to the Age-Related Eye Disease Study (AREDS), where subset of AREDS subjects at two sites were studied at two time points, an average of 1.7 and 6.7 years after enrollment. METHODS: Plasma glutathione (GSH), glutathione disulfide (GSSG), cysteine (Cys), and cystine (CySS) were measured by high-performance liquid chromatography, and redox potentials of GSH/GSSG (E(h) GSH) and Cys/CySS (E(h) Cys) were calculated. The means of the metabolites and redox potentials were compared by repeated-measures analysis of variance for subjects receiving antioxidants and those not receiving antioxidants. RESULTS: At the first blood draw, the means for the antioxidant group (n = 153) and no antioxidant group (n = 159) were not significantly different for any of the metabolites or redox potentials. At the second draw, the GSH parameters were not significantly different between the antioxidant (n = 37) and no antioxidant (n = 45) groups; however, mean Cys was significantly higher in the antioxidant group (9.5 vs 7.2 micromol/l, P = .008). Also, mean E(h) Cys was significantly more reduced in the antioxidant group (-74 vs -67.3 mV, P = .03). CONCLUSIONS: The AREDS antioxidant supplements reduced oxidation of E(h) Cys but had no effect on GSH. Because Cys is important for cell growth, apoptosis, and immune function, the beneficial effect of antioxidant supplementation on progression to advanced AMD may be partially explained by its effect on E(h) Cys and/or its effect on Cys availability.

Jiang S, Moriarty-Craige SE, Orr M, Cai J, Sternberg P, Jones DP. · Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, USA. · Invest Ophthalmol Vis Sci. · Pubmed #15728565 links to  free full text

Abstract: PURPOSE: To test whether variation in extracellular cysteine (Cys) redox potential (E(h)) over the physiologic range occurring in human plasma affects oxidant-induced apoptosis in cultured human retinal pigment epithelial (hRPE) cells. METHODS: The hRPE cells were incubated in culture medium with E(h) established over the range of -16 mV (most oxidized) to -158 mV (most reduced) by adding different concentrations of Cys and cystine (CySS) with constant total Cys equivalents. Apoptosis was induced with tert-butylhydroperoxide (tBH). RESULTS: The hRPE cells were sensitized to tBH-induced apoptosis in the more oxidized extracellular conditions (E(h) > -55 mV) compared with the reduced conditions (E(h) < -89 mV). Loss of mitochondrial membrane potential (Deltapsi(m)), release of cytochrome c, and activation of caspase 3 after tBH treatments all increased under the more oxidized conditions. However, the extracellular redox state did not affect expression of Fas or FasL in hRPE cells. CONCLUSIONS: The hRPE cells that are exposed to a more oxidized extracellular redox environment have increased susceptibility to oxidant-induced apoptosis through the intrinsic mitochondrial pathway, which could contribute to an age-related decline in cell populations in the retina and thereby provide a potential mechanism for the degenerative changes that are associated with age-related macular degeneration (ARMD).

Moshfeghi DM, Kaiser PK, Grossniklaus HE, Sternberg P, Sears JE, Johnson MW, Ratliff N, Branco A, Blumenkranz MS, Lewis H. · Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. · Am J Ophthalmol. · Pubmed #12614752 No free full text.

Abstract: PURPOSE: To report the clinicopathologic findings after submacular removal of choroidal neovascular membranes (CNV) treated with verteporfin ocular photodynamic therapy. DESIGN: Interventional case series. METHODS: Retrospective review of eight eyes of eight patients who underwent submacular surgery for CNV after having previously received verteporfin ocular photodynamic therapy for presumed ocular histoplasmosis (one patient), age-related macular degeneration ([AMD] three patients) pathologic myopia (two patients), punctate inner choroiditis (one patient), and idiopathic CNV (one patient). All cases had undergone ocular photodynamic therapy with verteporfin using standard protocols. Six of eight patients suffered a submacular hemorrhage after ocular photodynamic therapy, and two of eight patients refused further ocular photodynamic therapy. All patients subsequently had submacular surgery with removal of the CNV. One membrane was routinely processed, sectioned, and stained with hematoxylin and eosin. Five membranes were stained with toluidine blue for light microscopic examination. Semithin (1.0 microm) sections were cut and stained with uranyl acetate-lead citrate for transmission electron microscopy. RESULTS: Choroidal neovascular membranes were removed at 3 days (presumed ocular histoplasmosis), 29 days (punctate inner choroiditis), 63 days (AMD, pathologic myopia), 66 days (AMD), 107 days (pathologic myopia), 116 days (AMD), and 152 days (idiopathic) after verteporfin ocular photodynamic therapy. Histopathologic and ultrastructural examination showed areas of vascular occlusion at 3 days that were not seen at later time points. All specimens had patent CNV. There were signs of vascular damage with extravasated erythrocytes and fibrin, pigment clumping in cells, and inflammatory cells in all but the 3-day specimen.CONCLUSIONS: This case series presents data only from patients who refused repeat treatment with ocular photodynamic therapy or who developed submacular hemorrhage after initial photodynamic therapy. Histopathologic evaluation of CNV 3 days after verteporfin ocular photodynamic therapy showed partial vascular occlusion that was not present in later specimens. These later specimens demonstrated evidence of vascular damage. Verteporfin ocular photodynamic therapy does not appear to lead to permanent and complete occlusion of the CNV. Thus, treatments that lead to permanent closure of CNV without damage to the retinal pigment epithelium and sensory retina are still needed.

Sears J, Capone A, Aaberg T, Lewis H, Grossniklaus H, Sternberg P, DeJuan E. · Cleveland Clinic Eye Institute, The Cleveland Foundation, Ohio, USA. · Ophthalmology. · Pubmed #10328390 No free full text.

Abstract: OBJECTIVE: To report the authors' clinical experience with submacular surgery for subfoveal membranes in children and to evaluate the histopathologic findings of membranes in children with various etiologies of choroidal neovascularization. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Twelve eyes of 12 consecutive children with subfoveal choroidal neovascularization treated by vitrectomy and excision of the choroidal neovascular complex. INTERVENTION: Vitrectomy, excision of the choroidal neovascular complex, and air-fluid exchange. MAIN OUTCOME MEASURES: Visual acuity and recurrence of choroidal neovascular membrane. RESULTS: Preoperative visual acuities ranged from 20/60 to 20/800 (median, 20/300). Postoperative visual acuities ranged from 20/25 to 20/400 (median, 20/80) after an average follow-up of 20 months (range, 7-62 months). Ten of 12 eyes improved from immediate preoperative visual acuity, and four eyes developed recurrence of neovascular membranes over a mean follow-up of 18 months. Histopathologic examination of six excised membranes showed that the most common components of the membranes were retinal pigment epithelium, fibrocytes, vascular endothelium, and collagen. CONCLUSION: Selected eyes of children with subfoveal neovascular membranes and no evidence of membrane regression may benefit from submacular surgery. The histopathologic findings were similar to adult choroidal neovascularization not associated with age-related macular degeneration.