Macular Degeneration: Sunness JS

Sunness JS. · No affiliation provided · Br J Ophthalmol. · Pubmed #16547309 links to  free full text

This publication has no abstract.

Sunness JS. · The Wilmer Ophthalmological Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. · Mol Vis. · Pubmed #10562649 links to  free full text

Abstract: Geographic atrophy is the advanced form of atrophic age-related macular degeneration. It is present in 3.5% of people age 75 and over in the United States. It progresses gradually over time, often sparing the fovea until late in the course of the disease. Forty to fifty percent of eyes with geographic atrophy and good visual acuity at baseline lose three or more lines of acuity by two years and 27% become worse than 20/200 by four years. This article discusses the information known about age-related geographic atrophy at the present time.

Adackapara CA, Sunness JS, Dibernardo CW, Melia BM, Dagnelie G. · Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Retina. · Pubmed #18185146 No free full text.

Abstract: PURPOSE: To describe, in a group of patients with moderately advanced retinitis pigmentosa (RP), the prevalence of cystoid macular edema (CME), the variation in foveal thickness over a 48-week period, the correlation of visual acuity (VA) with retinal thickness, and the lack of response of CME to lutein administration. METHODS: Optical coherence tomography (OCT) imaging of the macula and clinical examination were evaluated for 77 eyes of 39 patients with RP over 11 months, with a scan done every 6 weeks. RESULTS: The prevalence of CME, defined by cysts visible on OCT, was 49%. Bilateral CME was present in 44% of patients (17 of 39), and an additional two patients had unilateral CME. Central retinal thickness varied little over the 48 weeks. Sixty-six percent of the eyes with CME had VA of 20/40 or better. The eyes with CME with VA worse than 20/40 had either greater degrees of thickening or in fact had lower thickness measures. For the eyes without CME, the eyes with VA worse than 20/40 tended to have lower retinal thickness than the eyes with VA of 20/40 or better. VA was highly concordant between eyes, and did not differ significantly between the groups with and without CME. Lutein did not show a statistically significant effect on retinal thickness in the patients with or without CME, nor was such an effect observed in subgroups of patients with vision better or worse than 20/40. CONCLUSION: The prevalence rate of CME is higher than in previous reports, perhaps because the patients had some preserved macular vision and because of the use of a definition based on OCT findings. Retinal thickness remains fairly stable over time, both in eyes with CME and in eyes without CME.

Sunness JS, Applegate CA, Gonzalez-Baron J. · Lions Vision Research and Rehabilitation Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Retina. · Pubmed #10783949 No free full text.

Abstract: PURPOSE: To study the improvement in visual acuity over time in patients with central scotomas. METHODS: In a prospective natural history study of geographic atrophy (GA) from age-related macular degeneration (ARMD) with annual follow-up, 36 patients with bilateral GA completed 3 years of follow-up. Protocol visual acuity (VA) measurements were performed. Scanning laser ophthalmoscopy (SLO) was performed, and the areas of GA were measured from fundus photographs. RESULTS: Six eyes of six patients with VA ranging from 20/80 to 20/500 had a VA improvement of two or more lines (mean, 3.2 lines). This was found only in the worse-seeing eyes of the patients and was contemporaneous with the deterioration in VA of the better-seeing eyes. Four of six eyes that improved in acuity had an improvement in the ability to find and hold the fixation target in an area of seeing retina, as assessed by SLO at follow-up, and a fifth eye changed from one fixation site that had little functional retina to another site. CONCLUSIONS: Spontaneous improvement in VA in eyes with bilateral GA and central scotomas may occur. It appears to be related to deterioration in VA of the better-seeing fellow eye and is associated with improvement of fixation in the worse-seeing eye. The worse-seeing eye of a patient with bilateral ARMD may have the potential for better vision than measured VA indicates. This finding may have implications for the choice of patients in treatment trials, for interpretation of long-term results, and for planning and assessment of low vision intervention.

Yang Z, Stratton C, Francis PJ, Kleinman ME, Tan PL, Gibbs D, Tong Z, Chen H, Constantine R, Yang X, Chen Y, Zeng J, Davey L, Ma X, Hau VS, Wang C, Harmon J, Buehler J, Pearson E, Patel S, Kaminoh Y, Watkins S, Luo L, Zabriskie NA, Bernstein PS, Cho W, Schwager A, Hinton DR, Klein ML, Hamon SC, Simmons E, Yu B, Campochiaro B, Sunness JS, Campochiaro P, Jorde L, Parmigiani G, Zack DJ, Katsanis N, Ambati J, Zhang K. · Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China. · N Engl J Med. · Pubmed #18753640 links to  free full text

Abstract: BACKGROUND: Age-related macular degeneration is the most common cause of irreversible visual impairment in the developed world. Advanced age-related macular degeneration consists of geographic atrophy and choroidal neovascularization. The specific genetic variants that predispose patients to geographic atrophy are largely unknown. METHODS: We tested for an association between the functional toll-like receptor 3 gene (TLR3) variant rs3775291 (involving the substitution of phenylalanine for leucine at amino acid 412) and age-related macular degeneration in Americans of European descent. We also tested for the effect of TLR3 Leu and Phe variants on the viability of human retinal pigment epithelial cells in vitro and on apoptosis of retinal pigment epithelial cells from wild-type mice and Tlr3-knockout (Tlr3(-/-)) mice. RESULTS: The Phe variant (encoded by the T allele at rs3775291) was associated with protection against geographic atrophy (P=0.005). This association was replicated in two independent case-control series of geographic atrophy (P=5.43x10(-4) and P=0.002). No association was found between TLR3 variants and choroidal neovascularization. A prototypic TLR3 ligand induced apoptosis in a greater fraction of human retinal pigment epithelial cells with the Leu-Leu genotype than those with the Leu-Phe genotype and in a greater fraction of wild-type mice than Tlr3(-/-) mice. CONCLUSIONS: The TLR3 412Phe variant confers protection against geographic atrophy, probably by suppressing the death of retinal pigment epithelial cells. Since double-stranded RNA (dsRNA) can activate TLR3-mediated apoptosis, our results suggest a role of viral dsRNA in the development of geographic atrophy and point to the potential toxic effects of short-interfering-RNA therapies in the eye.

Sunness JS, Rubin GS, Broman A, Applegate CA, Bressler NM, Hawkins BS. · The Richard E Hoover Rehabilitation Services for Low Vision and Blindness, Greater Baltimore Medical Center, Baltimore, Maryland 21204, USA. · Ophthalmology. · Pubmed #18486216 No free full text.

Abstract: OBJECTIVE: To show that low luminance visual dysfunction is predictive of subsequent visual acuity (VA) loss in eyes with geographic atrophy (GA) resulting from age-related macular degeneration (AMD). DESIGN: Cohort study examining the prospective natural history study of GA from 1992 through 2000 at the Wilmer Eye Institute. PARTICIPANTS: Ninety-one participants with GA resulting from AMD without choroidal neovascularization in at least 1 eye who completed a 2-year study examination. METHODS: Annual examinations included measurement of best-corrected VA, low luminance VA, Pelli-Robson contrast sensitivity, reading speed, examination, and fundus photography. The total GA area was quantified, as was the GA within a 10.2-mm(2) circle centered on the fovea. MAIN OUTCOME MEASURES: Visual acuity loss at 2 years and risk factors for visual loss. RESULTS: Participants with baseline VA of 20/50 or more had a 40% 2-year rate of VA loss of 3 lines or more, compared with 13% for the participants with worse baseline acuities. The baseline low-luminance deficit (LLD) in VA was a strong predictor of subsequent VA loss for all levels of baseline VA. Within the good baseline VA group, the relative risk (RR) of 3-line loss for the worse LLD group compared with the better LLD group was 2.88 (95% confidence interval [CI], 1.13-7.35). The LLD is a stable and reproducible measure. Other significant visual function predictors of subsequent VA loss in eyes with good baseline VA included foveal dark-adapted sensitivity (RR, 4.20; 95% CI, 1.39-12.71) and reduced reading rate (RR, 2.43; 95% CI, 1.11-5.31). The rate of VA loss within the good acuity group was higher when the GA included 25% to 75% of the central 10.2 mm(2) than in eyes with GA including less than 25% or more than 75% of the central 10.2 mm(2). The following were not significant predictors of subsequent VA loss among these participants: age, gender, fellow eye diagnosis, fellow eye VA, baseline GA area, and GA enlargement rate. CONCLUSIONS: Visual function measures can predict the risk of future VA loss in subjects with GA and good baseline VA. They may allow identification of the highest risk group for VA loss, enabling more efficient design of clinical trials. They also may be appropriate surrogate measures of foveal health in short-term treatment trials.

Sunness JS, Applegate CA, Bressler NM, Hawkins BS. · Richard E. Hoover Rehabilitation Services for Low Vision and Blindness, Greater Baltimore Medical Center, Baltimore, Maryland 21204, USA. · Retina. · Pubmed #17290203 No free full text.

Abstract: PURPOSE: To derive information from the Geographic Atrophy (GA) Natural History Study that is relevant to recruiting patients and designing clinical trials for GA. METHODS: A prospective natural history study with annual follow-up enrolled patients with GA and no choroidal neovascularization (CNV) in at least one eye. Characteristics of recruited and enrolled patients are analyzed, in the context of progression data from the study. RESULTS: The data show that GA from age-related macular degeneration (AMD) was seen in 82% of the referred patients, there was an attrition rate of 14%, and 60% of the patients with GA from AMD had bilateral GA without CNV. Within the 83 patients in the bilateral GA group with follow-up, 50 patients (60%) met both the proposed visual acuity and the proposed GA area criteria for a treatment trial in one or both eyes. CONCLUSION: These data should be helpful in planning future treatment trials for GA.

Sunness JS, Margalit E, Srikumaran D, Applegate CA, Tian Y, Perry D, Hawkins BS, Bressler NM. · Richard E. Hoover Rehabilitation Services for Low Vision and Blindness, Greater Baltimore Medical Center, Baltimore, Maryland 21204, USA. · Ophthalmology. · Pubmed #17270676 links to  free full text

Abstract: PURPOSE: To report the enlargement rate of geographic atrophy (GA) over time, its relationship to size of atrophy at baseline and to prior enlargement rate, and the implications for designing future treatment trials for GA. DESIGN: Prospective natural history study of GA resulting from age-related macular degeneration. PARTICIPANTS: Two hundred twelve eyes of 131 patients were included in the analysis. METHODS: Annual follow-up included stereo color fundus photographs. The areas of GA were identified and measured, and the rate of enlargement of the atrophy was assessed. Sample sizes for clinical trials using systemic treatment and uniocular treatment were determined. MAIN OUTCOME MEASURE: Rate of enlargement of the atrophy. RESULTS: The median overall enlargement rate was 2.1 mm2/year (mean, 2.6 mm2/year). Eyes with larger areas of atrophy at baseline tended to have larger enlargement rates, but knowledge of prior rates of enlargement was the most significant factor in predicting subsequent enlargement rates. There was high concordance between the enlargement rates in the 2 eyes of patients with bilateral GA (correlation coefficient, 0.76). To detect a 25% reduction in enlargement rate for a systemic treatment (alpha, 0.05; power, 0.80; losses to follow-up, 15%), 153 patients each in a control and treatment group would be required for a trial with a 2-year follow-up period for each patient. For a uniocular treatment, 38 patients with bilateral GA would be required, with the untreated eye serving as a control for the treated eye. CONCLUSIONS: Treatment trials for GA with an outcome variable of change in enlargement rate are feasible.

Sunness JS, Ziegler MD, Applegate CA. · Richard E. Hoover Rehabilitation Services for Low Vision and Blindness, the Greater Baltimore Medical Center, Maryland 21204, USA. · Retina. · Pubmed #16829810 No free full text.

Abstract: PURPOSE: To demonstrate the potential and limits of autofluorescence imaging in identifying and delineating areas of atrophy. METHODS: Fundus photographs and infrared scanning laser ophthalmoscope (SLO) imaging, SLO macular perimetry, and SLO autofluorescence imaging results were compared for two patients with geographic atrophy (GA) from age-related macular degeneration, one patient with pigmentary alteration of the retina, and two patients with Stargardt disease. The main outcome measure in this case series was the presence of reduced autofluorescence. RESULTS: Drusen may become undetectable during autofluorescence imaging for some patients, allowing simple identification of areas of GA with areas of reduced autofluorescence. In other patients, drusen themselves have decreased autofluorescence, despite having intact retinal function in the retina overlying them. Some patients may have areas of reduced autofluorescence that persist for many years, without evidence of the development of atrophy. In Stargardt disease, decreased autofluorescence can easily detect and delineate areas of scotoma. Areas with mottled autofluorescence may have overlying function, but the function may not be adequate to support a fixation locus in that area. CONCLUSIONS: Using decreased autofluorescence to delineate areas of atrophy may be helpful in atrophic macular disorders. For GA, correlation with fundus photographs or macular perimetry findings may be necessary to differentiate between drusen and atrophy. For Stargardt disease, the nature of areas of decreased autofluorescence may help explain visual function of those areas.

Sunness JS, Applegate CA. · Greater Baltimore Medical Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21204, USA. · Am J Ophthalmol. · Pubmed #16376656 links to  free full text

Abstract: PURPOSE: To study whether fixation patterns changed over time in patients with central scotomas from geographic atrophy from age-related macular degeneration. DESIGN: Prospective cohort study. METHODS: setting: Institutional. patient or study population: Prospective natural history study of geographic atrophy included 34 eyes of 25 patients with baseline acuity between 20/80 and 20/200 and with subsequent follow-up. observation procedures: Baseline and annual follow-up visits included best-corrected visual acuity, scanning laser ophthalmoscope macular perimetry, reading rate, and clinical evaluation. main outcome measures: Location of eccentric preferred retinal locus for fixation (PRL). RESULTS: At baseline, 77% of study eyes had a PRL. At the final visit (median follow-up, 5.3 years), 91% of study eyes had a PRL, with 81% of the eyes retaining the baseline PRL location. Fixation with the scotoma to the right and fixation with the scotoma superior were the first and second most common fixation patterns, respectively. Reading rates of <50 words/min were present in 54% of eyes. Eyes fixating with the scotoma to the left tended to have lower reading rates than eyes fixating with right or superior patterns. CONCLUSION: Fixation with right pattern remained the most common fixation pattern, both in patients with a PRL at baseline and in patients who had a PRL during follow-up. Eyes with a PRL at baseline generally retained this pattern. The reading rate data suggest an advantage of fixation with right or superior pattern, rather than left. Reading rate declined further during follow-up in most patients.

Sunness JS, Liu T, Yantis S. · Lions Vision Center of the Wilmer Ophthalmologic Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. · Ophthalmology. · Pubmed #15288993 No free full text.

Abstract: PURPOSE: To describe retinotopic mapping of the visual cortex when a central scotoma is present. DESIGN: Single observational case report. METHODS: Scanning laser ophthalmoscope perimetry was used to define the site and stability of fixation and the area of dense scotoma. Functional magnetic resonance imaging of the visual cortex was performed while the patient viewed an expanding annular stimulus. RESULTS: Retinotopic mapping of the visual cortex for a patient with a horseshoe scotoma from geographic atrophy involving the macular region showed a loss of stimulation to the cortical areas representing the site of the atrophic lesion. CONCLUSIONS: Cortical retinotopic mapping can be performed successfully in patients with central scotomas from macular disease. This study can serve as a basis for the future investigation of cortical plasticity in visual cortex.

Fujii GY, De Juan E, Humayun MS, Sunness JS, Chang TS, Rossi JV. · Doheny Retina Institute, Doheny Eye Institute, University of Southern California, Keck School of Medicine, Los Angeles, California 90033, USA. · Am J Ophthalmol. · Pubmed #14644217 No free full text.

Abstract: PURPOSE: To evaluate the effects of subfoveal choroidal neovascularization secondary to age-related macular degeneration on functional parameters obtained by scanning laser ophthalmoscope microperimetry. DESIGN: Retrospective observational case series and cross-sectional study. METHODS: At the Doheny Retina Institute and Wilmer Eye Institute a consecutive series of 179 eyes of 175 patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration was studied. The onset of visual symptoms, best-corrected visual acuity, fluorescein angiography, evaluation of fundus microperimetry and fixation pattern using the Rodenstock scanning laser ophthalmoscope were obtained for each patient. The main outcome measures were central retinal sensitivity and fixation pattern (fixation location and fixation stability) in eyes with subfoveal choroidal neovascularization and their relationship to the length of disease, type and characteristics of choroidal neovascularization, and visual acuity. RESULTS: Of 179 eyes, 135 (75%) had central fixation, 27 (15%) had poor central fixation, and 17 (9%) had predominantly eccentric fixation. Seventy-six eyes (42%) had stable fixation, 70 eyes (39%) had relatively unstable fixation, and 33 eyes (18%) had unstable fixation. In 50 eyes (28%) a dense central scotoma was noted. Eighty-nine of 100 eyes (89%) with length of symptoms of less than 3 months had predominantly central fixation and 58 (58%) had stable fixation; 14 of 34 eyes (41%) with length of symptoms of more than 6 months had predominantly central fixation, and 5 eyes (15%) had stable fixation. In 15 eyes of patients who elected not to receive treatment, successive scanning laser ophthalmoscope microperimetry were obtained over time (follow-up of 18 months after onset of symptoms). Three months or less after the onset of symptoms, 13 eyes (87.7%) had predominantly central fixation and 9 eyes (60%) had stable fixation. More than 3 months and 6 months or less after the onset of symptoms, 10 eyes (66.7%) had predominantly central fixation and 7 eyes (46.7%) had stable fixation. This trend was further demonstrated in eyes more than 6 months after the onset of symptoms. CONCLUSIONS: We conclude that the sequence of events leading to visual function deterioration appears to involve an initial mild decrease in central retinal sensitivity and visual acuity followed by progressive fixation instability and, ultimately, development of an absolute central scotoma with totally eccentric fixation. Increased length of disease is associated with worse fixation pattern and retinal sensitivity deterioration as assessed by scanning laser ophthalmoscope microperimetry. A better understanding of the characteristics of visual loss assessed by fixation pattern evaluation and microperimetry in age-related macular degeneration may help optimize timing, patient selection, and treatment options in eyes with this condition.

Margalit E, Sunness JS, Green WR, Kelman SE, Schachat AP, Fiergang D, Allikmets R. · Wilmer Eye Institute, Baltimore, Maryland 21205, USA. · Arch Ophthalmol. · Pubmed #14609928 No free full text.

This publication has no abstract.

Pianta MJ, Aleman TS, Cideciyan AV, Sunness JS, Li Y, Campochiaro BA, Campochiaro PA, Zack DJ, Stone EM, Jacobson SG. · Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, 51 N, 39th Street, Philadelphia, PA 19104, USA. · Exp Eye Res. · Pubmed #12565808 No free full text.

Abstract: Best macular dystrophy (BMD) is an autosomal dominant retinopathy caused by mutations in the VMD2 gene that encodes a chloride channel in the basolateral membrane of the retinal pigment epithelium (RPE). BMD patients were studied using optical coherence tomography (OCT) to understand the disease process in the macula leading to vision loss. BMD patients (ages 5-61), representing four families with known VMD2 mutations, were included. OCT scans were recorded in the central retina and longitudinal reflectivity profiles were analysed. The central retina in BMD showed different OCT abnormalities at or near the level of the highly reflective deep retinal band termed the outer retina-choroid complex (ORCC). Two types of ORCC change were noted to occur either separately or together: (1) splitting with or without intervening hyporeflective areas; and (2) elevation. Longitudinal study of a BMD patient indicated that such abnormalities were dynamic and changed in type and degree with time. The pathogenetic sequence in BMD may begin with defective fluid transport across the RPE secondary to the channelopathy in the basolateral membrane. In the macula, this leads to an abnormal interface with adjacent structures at both apical and basal surfaces of the RPE. The disease process results in detachments of the neurosensory retina, such as in central serous chorioretinopathy, and sub-RPE pathology resembling some stages of age-related macular degeneration, with eventual loss of photoreceptors, inner retina and central vision.

McLeod DS, Taomoto M, Otsuji T, Green WR, Sunness JS, Lutty GA. · Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, Maryland 21287-9115, USA. · Invest Ophthalmol Vis Sci. · Pubmed #12037009 links to  free full text

Abstract: PURPOSE: An image-analysis technique was developed to quantify changes in the retinal pigment epithelium (RPE) and choriocapillaris in eyes of deceased donors with age-related macular degeneration (AMD). METHODS: Both eyes of two donors with AMD and of one normal control donor were used to develop this technique. After removal of the anterior segments, the eyecups were hemisected through the macula, with the disc included in one half of the eyecup. The choroid with RPE cells was dissected from the sclera and incubated for alkaline phosphatase (APase) activity, and the pigment was partially bleached with H2O2. The APase-incubated choroid was flat embedded and sectioned after image and morphometric analyses. Quantitative computer-assisted morphometric analyses of the two AMD-affected eyes (cases 1 and 2) were compared with analysis of the normal eye of a 70-year-old control subject (case 3). RESULTS: The right eye in case 1 had geographic atrophy (GA) and demonstrated a large area in the posterior pole with very few RPE cells (90% loss of RPE), but the border of the area of RPE atrophy was not well defined. The density of choroidal blood vessels in this area was reduced 30% to 50%, compared with the same regions in the control eye. No area was completely devoid of choriocapillaris. Clinically undetected choroidal neovascularization (CNV) was observed in the right eye in case 1 in both the periphery and the macula and was generally associated with surviving RPE cells. The right eye in case 2 had GA (areolar RPE atrophy) and demonstrated a reduction in vascular density in the area from disc to macula that was even greater than that in the eye in case 1 (53% reduction in the submacular region). RPE atrophy between the disc and macula was almost complete. The border of the RPE defect was clearly delineated and coincided closely with the area of decreased choroidal vascular density. Surviving choriocapillaris in the area of RPE atrophy was significantly narrower than choriocapillaris in the control subject and in normal areas of the eyes with GA (P < 0.0001). CONCLUSIONS: In these eyes with GA, RPE atrophy was more severe than loss of choriocapillaris. Surviving choriocapillaris in areas with complete RPE loss was highly constricted. The association of surviving RPE cells with CNV suggests that RPE cells may furnish a stimulus for new vessel formation or stabilization.

Zhang K, Garibaldi DC, Kniazeva M, Albini T, Chiang MF, Kerrigan M, Sunness JS, Han M, Allikmets R. · Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Am J Ophthalmol. · Pubmed #10612508 No free full text.

Abstract: PURPOSE: To identify additional mutations in the ABCR gene and describe the clinical features of four affected siblings with autosomal recessive Stargardt disease. METHODS: A cohort of eight siblings was identified for study. Four of these individuals were diagnosed with Stargardt disease based on clinical evaluation and fluorescein angiography. Blood samples were obtained from seven of eight siblings, including all those affected. All 50 exons of the ABCR gene were analyzed by single-stranded confirmation polymorphism analysis, followed by direct sequencing of observed variants, to identify mutations in the ABCR gene. RESULTS: We identified a previously unreported kindred of eight siblings, four of whom had mutations in both of their ABCR alleles. A previously described G-to-C transversion of nucleotide 2588, predicting a Gly863Ala amino acid substitution, and a novel G-to-A transition of nucleotide 161, resulting in a Cys54Tyr substitution, were identified. These mutations co-segregated with the affected members of this family. Three of the siblings demonstrated clinical features characteristic of classic Stargardt disease, with bilateral regions of macular atrophy associated with yellow-white "flavimaculatus" flecks in the posterior pole at the level of the retinal pigment epithelium. The fourth affected sibling showed features of early Stargardt disease, with a beaten-bronze appearance to both maculas, as well as perimacular flecks. In all four affected patients, fluorescein angiography showed a characteristic peripheral dark choroid. CONCLUSIONS: We have identified both a previously described and a novel mutation in the ABCR gene in four patients with autosomal recessive Stargardt disease. In-depth knowledge of the ABCR mutation spectrum in patients with Stargardt disease will provide for more efficient screening and may provide potential therapies for Stargardt disease and other retinal diseases.

Weisz JM, Humayun MS, De Juan E, Del Cerro M, Sunness JS, Dagnelie G, Soylu M, Rizzo L, Nussenblatt RB. · Department of Ophthalmology, Wilmer Ophthalmological Institute, Johns Hopkins Medical Institutes, Baltimore, Maryland 21287, USA. · Retina. · Pubmed #10606456 No free full text.

Abstract: PURPOSE: To test the hypothesis that healthy fetal retinal pigment epithelium (RPE) can rescue the remaining viable RPE and choriocapillaries and thereby the photoreceptors in non-neovascular age-related macular degeneration (ARMD) (geographic atrophy [GA]). METHODS: A 65-year-old legally blind woman with non-neovascular ARMD underwent fetal RPE transplantation. Best-corrected visual acuity testing, detailed fundus examination, fundus photography, fluorescein angiography, scanning laser ophthalmoscope macular perimetry, and humoral and cellular immune response testing were performed. A suspension of RPE was infused into the subretinal space through a retinotomy along the superotemporal arcade at the edge of the area of GA. The patient did not take systemic immunosuppressants. RESULTS: The patient's vision remained unchanged for 5 months after the surgery. Fluorescein angiography after transplantation showed leakage and staining at the level of the outer retina. There was progressive subretinal fibrosis in the area of the transplant. Immune response studies showed a weakly positive mixed lymphocyte response against phosducin and rhodopsin. CONCLUSION: Although it is surgically feasible to transplant fetal RPE to the subretinal space of patients with GA, such an allogenic RPE transplant without immunosuppression leads to leakage on fluorescein angiography and eventual fibrosis. A very weak immune response against proteins associated with photoreceptors is also of concern.

Sunness JS, Gonzalez-Baron J, Applegate CA, Bressler NM, Tian Y, Hawkins B, Barron Y, Bergman A. · Wilmer Ophthalmological Institute, Lions Vision Research and Rehabilitation Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Ophthalmology. · Pubmed #10485549 No free full text.

Abstract: OBJECTIVE: To describe the progression of geographic atrophy (GA) from age-related macular degeneration (AMD) with respect to visual acuity (VA) loss and enlargement of atrophy. DESIGN: A prospectively observed case series. SETTING: Tertiary retinal referral center. PARTICIPANTS: One hundred twenty-three patients with GA due to AMD who completed at least 1 year of follow-up (median follow-up, 3 years) were examined annually. METHODS: At each examination, a protocol best-corrected VA of each eye was measured, a clinical examination was performed, and color fundus photographs were taken. The areas of atrophy were drawn and measured. MAIN OUTCOME MEASURES: Visual acuity loss and enlargement of total and central atrophy. RESULTS: At baseline, median VA was poorer with larger areas of atrophy, but there was wide variation related to sparing of the fovea. Thirty-one percent of all study eyes suffered a three-line VA loss from baseline by 2 years, and 53% had a three-line loss by 4 years. Those eyes with VA better than 20/50 had the highest rate of acuity loss; 27% of these eyes had acuities of 20/200 or worse at 4 years. Visual acuity loss in the GA study eye was similar in patients with bilateral GA and in those with choroidal neovascularization in the fellow eye. Total atrophy enlarged a median of 1.8 Macular Photocoagulation Study disc areas (DA) at 2 years; atrophy within a 4-DA circle centered on the fovea enlarged a median of 0.9 DA. Two (22%) of nine patients with GA in one eye and only drusen without advanced AMD in the fellow eye developed GA in the fellow eye at 2 years. CONCLUSIONS: Geographic atrophy is associated with a significant decline in VA over time in many eyes. Areas of atrophy continue to enlarge over time, even when already large at baseline. The combination of reduced VA with enlargement of atrophy, occurring bilaterally in most patients, can lead to significant impairment of visual function.

Sunness JS, Bressler NM, Tian Y, Alexander J, Applegate CA. · Lions Low Vision Center, The Wilmer Ophthalmological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. · Invest Ophthalmol Vis Sci. · Pubmed #10393046 links to  free full text

Abstract: PURPOSE: To present a method developed for measuring areas of geographic atrophy (GA) in advanced age-related macular degeneration, METHODS: A microfilm reader projected the 30 degrees fundus photograph of the macula. Retinal landmarks, atrophic areas, and spared areas within the atrophy were traced, without access to drawings of other years. The total atrophic area was calculated, as was the atrophy within a four-disc-area circle entered on the estimated foveal center. The configuration of the atrophy was documented. RESULTS: Avoidable sources of discrepancy included variability in peripapillary atrophy seen on the photograph, and variability seen in the extent of the field. Reproducibility studies found a median absolute difference of 0.19 Macular Photocoagulation Study disc areas (DA) in total atrophy between repeat drawings, with 75% of repeat drawings having a difference of less than 0.33 DA. For central atrophy measures, there was a median difference of 0.08 DA, with 75% of pairs having a difference of less than 0.18 DA. Features making the definition of borders of GA difficult include the presence of drusen and pigmentary alteration, a fundus in which choroidal vessels are easily visible, and variation in the appearance of GA within a single area of atrophy. CONCLUSIONS: This method provides a reliable means of measuring the size of atrophic areas in GA and will be useful for measuring longitudinal change. It may be difficult to determine whether central spared areas are present, and correlation with visual acuity and macular perimetry may be helpful.

Sunness JS, Gonzalez-Baron J, Bressler NM, Hawkins B, Applegate CA. · Lions Vision Research and Rehabilitation Center, Baltimore, Maryland, USA. · Ophthalmology. · Pubmed #10328389 No free full text.

Abstract: OBJECTIVE: To determine the rate of developing choroidal neovascularization (CNV) in eyes with geographic atrophy (GA) from age-related macular degeneration (AMD) and the characteristics of the CNV in these eyes. DESIGN: Prospective natural history study with cohort analysis. PARTICIPANTS: One hundred fifty-two patients with GA and no CNV by fluorescein angiography in at least 1 eye, with annual follow-up. MAIN OUTCOME MEASURES: The development of CNV. RESULTS: Thirteen eyes with GA developed CNV. For patients with bilateral GA and no CNV at baseline, 2% developed CNV by 2 years and 11% by 4 years. For patients with CNV in the fellow eye, 18% developed CNV in the study eye with GA by 2 years and 34% by 4 years. The eyes that developed CNV experienced more acuity loss than did the eyes with only GA. Within the fellow eye CNV group, those study eyes with GA that had less central atrophy (and better acuity) at baseline were more likely to develop CNV. The CNV developed at a peripheral border of GA in nine eyes, in the spared foveal region in two eyes, and in both center and border in one eye. No eye developed CNV in the area of atrophy itself. The appearance of CNV was evanescent in some cases and had a final appearance of an enlarged area of GA. Twelve other eyes had hemorrhages without definite evidence of CNV; three were thought to be suspicious for CNV and the remainder were thought to be hemorrhages that may be seen in elderly patients. CONCLUSION: An eye with GA whose fellow eye has CNV is at significant risk for the development of CNV in the GA eye. A patient with bilateral GA and no evidence of CNV is at relatively low risk for developing CNV. The CNV may be evanescent and may not be detected. Intraretinal hemorrhages unrelated to CNV are relatively common in this older population.

Apte RS, Sunness JS, Goldstein BG, Park WL, Sunness JS, Raden RZ, Elman MJ. · No affiliation provided · Br J Ophthalmol. · Pubmed #12881357 links to  free full text

This publication has no abstract.

Apte RS, Sunness JS, Goldstein BG, Park WL, Sunness JS, Raden RZ, Elman MJ. · No affiliation provided · Br J Ophthalmol. · Pubmed #12881357 links to  free full text

This publication has no abstract.