Advanced Macular Degeneration Research Articles

Early Choriocapillaris Loss in a Porcine Model of RPE Cell Debridement Precedes Pathology That Simulates Advanced Macular Degeneration.

No large-mammal surgical models exist for geographic atrophy (GA), choroidal neovascularization (CNV), and pachychoroidal vascular remodeling. Our goal was to develop a porcine RPE debridement model of advanced macular degeneration to study photoreceptor cell loss and choroidal remodeling. Seven 2-month-old female domestic pigs were used for this study. After 25G vitrectomy, the area centralis was detached via subretinal bleb. A nitinol wire (Finesse Flex Loop) was used to debride RPE cells across a 3- to 5-mm diameter region. Fluid-air exchange was performed, and 20% SF6 gas injected. Animals underwent fundus photography, fluorescein angiography, optical coherence tomography (OCT), and OCT-angiography (OCTA) at 2 weeks, 1month, 2months, 3months, and 6 months postoperatively. Retinal histology was obtained at euthanasia, 2months (n = 3), 3months (n = 2), or 6months (n = 2) after surgery. RPE debridement resulted in GA with rapid loss of choriocapillaris, progressive loss of photoreceptors, and pachychoroidal changes in Sattler's and Haller's layers in all seven eyes undergoing debridement within 2 months. OCT and histological findings included subretinal disciform scar with overlying outer retinal atrophy; outer retinal tubulations and subretinal hyper-reflective material. OCTA revealed type 2 CNV (n = 4) at the edges of the debridement zone by 2 months, but there was no significant exudation noted at any time point. Surgical debridement of the RPE results in GA, CNV, and pachychoroid and reproduced all forms of advanced macular degeneration. This surgical model may be useful in examining the role of RPE and other cell replacement in treating advanced macular disease.

Influence of Dietary Seafood on the Prevention of Ocular Disorders: A Clinical Analysis

Age-related macular degeneration, retinal dysfunction, dry eye syndromes, cataract formation, and the prevalence of other vision defects are directly related to nutrients in the diet. People consuming seafood are less prone to several vision disorders. The present study was designed to validate the view. In this study, 712 visitors to tertiary eye care for eye check-ups were interviewed using a standard questionnaire, and from them, 264 persons were identified with some ocular defects. The identified cases were further screened based on their dietary habits with seafood. The isolated cases were clinically examined, and the development of ocular defects such as macular edema, optic neuropathy, myopia, double vision, dry eye syndrome, and color blindness was recorded. The results show that the respondents taking one or another type of three fishes regularly have a low impact on visual disorders. Respondents with fish intake above 500 g/week were less affected by all five ocular disabilities tested when compared with occasional users. Among the total respondents, the percentage of visual defects was seen in 62.12% in seafood users, but among the non-seafood users, the presence of visual defects was 89.6%. Statistical analysis using the Pearson population correlation coefficient, ρ (rho), further confirmed the relationship between eye wellness and a seafood diet. The omega-3 fatty acids linked with vision were also high in the fish consumed by the people. This study confirms that a regular seafood diet is good for eye health and can prevent the epidemics of several eye diseases. As fish intake contains a good amount of long-chain polyunsaturated omega-3 fatty acids, people who consume fish in their diet are less susceptible to advanced macular degeneration and other vision impairments responsible for age-related blindness.

Bioprinted 3D outer retina barrier uncovers RPE-dependent choroidal phenotype in advanced macular degeneration.

Age-related macular degeneration (AMD), a leading cause of blindness, initiates in the outer-blood-retina-barrier (oBRB) formed by the retinal pigment epithelium (RPE), Bruch's membrane, and choriocapillaris. The mechanisms of AMD initiation and progression remain poorly understood owing to the lack of physiologically relevant human oBRB models. To this end, we engineered a native-like three-dimensional (3D) oBRB tissue (3D-oBRB) by bioprinting endothelial cells, pericytes, and fibroblasts on the basal side of a biodegradable scaffold and establishing an RPE monolayer on top. In this 3D-oBRB model, a fully-polarized RPE monolayer provides barrier resistance, induces choriocapillaris fenestration, and supports the formation of Bruch's-membrane-like structure by inducing changes in gene expression in cells of the choroid. Complement activation in the 3D-oBRB triggers dry AMD phenotypes (including subRPE lipid-rich deposits called drusen and choriocapillaris degeneration), and HIF-α stabilization or STAT3 overactivation induce choriocapillaris neovascularization and type-I wet AMD phenotype. The 3D-oBRB provides a physiologically relevant model to studying RPE-choriocapillaris interactions under healthy and diseased conditions.

Common and rare variants in patients with early onset drusen maculopathy.

Early onset drusen maculopathy (EODM) can lead to advanced macular degeneration at a young age, affecting quality of life. However, the genetic causes of EODM are not well studied. We performed whole genome sequencing in 49 EODM patients. Common genetic variants were analysed by calculating genetic risk scores based on 52 age-related macular generation (AMD)-associated variants, and we analysed rare variants in candidate genes to identify potential deleterious variants that might contribute to EODM development. We demonstrate that the 52 AMD-associated variants contributed to EODM, especially variants located in the complement pathway. Furthermore, we identified 26 rare genetic variants predicted to be pathogenic based on in silico prediction tools or based on reported pathogenicity in literature. These variants are located predominantly in the complement and lipid metabolism pathways. Last, evaluation of 18 genes causing inherited retinal dystrophies that can mimic AMD characteristics, revealed 11 potential deleterious variants in eight EODM patients. However, phenotypic characteristics did not point towards a retinal dystrophy in these patients. In conclusion, this study reports new insights into rare variants that are potentially involved in EODM development, and which are relevant for future studies unravelling the aetiology of EODM.

Evaluating the Occurrence of Rare Variants in the Complement Factor H Gene in Patients With Early-Onset Drusen Maculopathy

Early-onset drusen maculopathy (EODM) is a severe disease and can lead to advanced macular degeneration early in life; however, genetic and phenotypic characteristics of individuals with EODM are not well studied. To identify genotypic and phenotypic characteristics of individuals with EODM. This case-control study collected data from the European Genetic Database from September 2004 to October 2019. A total of 89 patients with EODM diagnosed at 55 years or younger and 91 patients with age-related macular degeneration (AMD) diagnosed at 65 years or older were included. Coding regions of CFH, CFI, C3, C9, CFB, ABCA4, PRPH2, TIMP3, and CTNNA1 genes were sequenced, genetic risk scores (GRS) were calculated based on 52 AMD-associated variants, and phenotypic characteristics on color fundus photographs were analyzed comparing patients with EODM and AMD. GRS, frequency of rare genetic complement variants, and phenotypic characteristics. This case-control study included 89 patients with EODM (mean [SD] age, 51.8 [8.7] years; 58 [65.2%] were female) and 91 patients with AMD (mean [SD] age, 77.6 [6.1] years; 45 [49.5%] female). At a mean (SD) age of 56.4 (7.3) years, 40 of 89 patients with EODM (44.9%) were affected by geographic atrophy or choroidal neovascularization. A lower GRS was observed in patients with EODM compared with patients with AMD (1.03 vs 1.60; P = .002), and 27 of 89 patients with EODM (30.3%) carried rare variants in the CFH gene compared with 7 of 91 patients with AMD (7.7%). Carriership of a rare CFH variant was associated with EODM (odds ratio, 7.2; 95% CI, 2.7-19.6; P < .001). A large macular drusen area (more than 50% covered with drusen) was observed in patients with EODM (24 of 162 eyes [14.8%]) compared with patients with AMD (9 of 164 eyes [5.5%]) (odds ratio, 4.57; 95% CI, 1.5-14.1; P = .008). A large proportion of patients with EODM in this study carried rare CFH variants, with most of the identified CFH variants clustered in the first 7 complement control protein domains affecting factor H and factor H-like 1. Because EODM frequently leads to advanced macular degeneration at an early age and can result in many years of vision loss, this study supports targeting the complement system and sequencing the CFH gene in patients with EODM to improve genetic counseling and future treatments for AMD.

Fractal Dimension Analysis of Widefield Choroidal Vasculature as Predictor of Stage of Macular Degeneration.

PurposeTo evaluate the fractal dimension (Df) of the choroidal vasculature using widefield indocyanine green (ICG) angiography and correlate it with the stage of age-related macular degeneration (AMD).MethodsWidefield ICG angiography performed on 38 eyes was retrospectively analyzed using the FracLac application within the National Institutes of Health ImageJ software to determine regional fractal dimensions in the macular field and widefield. These values were then associated with a diagnosis of no AMD, non-exudative AMD (subdivided into early/intermediate stage vs. advanced stage), or exudative AMD (subdivided into with or without geographic atrophy). The mean values were compared using Wilcoxon's test.ResultsEarly/intermediate non-exudative AMD and exudative AMD without geographic atrophy were found to have statistically significantly lower Df values compared to an absence of AMD when examining the macular field. Exudative AMD with geographic atrophy was found to have a statistically significant lower choroidal fractal dimension compared to no AMD when studied in the widefield.ConclusionsAdvanced stages of macular degeneration were found to have significantly decreased the fractal dimensions of choroidal vasculature on widefield ICG compared to early/intermediate stages, possibly implying a generalized reduction in complexity and/or vessel caliber of the choroid with advancing stage of AMD. This finding agrees with previous understanding of the development of choriocapillaris atrophy in advanced macular degeneration.Translational RelevanceThese findings suggest that using automated fractal analysis techniques can aid in differentiating stages of macular degeneration and, with further study, may be used to predict advancement of macular degeneration.

Altered photoreceptor metabolism in mouse causes late stage age-related macular degeneration-like pathologies

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. While the histopathology of the different disease stages is well characterized, the cause underlying the progression, from the early drusen stage to the advanced macular degeneration stage that leads to blindness, remains unknown. Here, we show that photoreceptors (PRs) of diseased individuals display increased expression of two key glycolytic genes, suggestive of a glucose shortage during disease. Mimicking aspects of this metabolic profile in PRs of wild-type mice by activation of the mammalian target of rapamycin complex 1 (mTORC1) caused early drusen-like pathologies, as well as advanced AMD-like pathologies. Mice with activated mTORC1 in PRs also displayed other early disease features, such as a delay in photoreceptor outer segment (POS) clearance and accumulation of lipofuscin in the retinal-pigmented epithelium (RPE) and of lipoproteins at the Bruch's membrane (BrM), as well as changes in complement accumulation. Interestingly, formation of drusen-like deposits was dependent on activation of mTORC1 in cones. Both major types of advanced AMD pathologies, including geographic atrophy (GA) and neovascular pathologies, were also seen. Finally, activated mTORC1 in PRs resulted in a threefold reduction in di-docosahexaenoic acid (DHA)-containing phospholipid species. Feeding mice a DHA-enriched diet alleviated most pathologies. The data recapitulate many aspects of the human disease, suggesting that metabolic adaptations in photoreceptors could contribute to disease progression in AMD. Identifying the changes downstream of mTORC1 that lead to advanced pathologies in mouse might present new opportunities to study the role of PRs in AMD pathogenesis.

Association between macular degeneration and mild to moderate chronic kidney disease: A nationwide population-based study.

Chronic kidney disease (CKD) and macular degeneration (MD) are 2 grave diseases leading to significant disability secondary to renal failure and blindness. The 2 diseases share not only common risk factors but also similar pathogenic mechanisms to renal and retinal injuries. Previous epidemiological studies indicated association between these 2 diseases. However, this concept is challenged by recent investigations. Patients with mild to moderate CKD (n = 30,696) between January 1, 1995 and December 31, 2005 were selected from the Taiwan National Health Insurance Database. Controls (n = 122,784) were matched by age, gender, diabetes mellitus type 2, and hypertension status (1:4 ratios). The risk of MD was compared between the 2 groups. The mean age of patients was 54.9 ± 15.7 years. The proportion of MD was 2.7% in mild to moderate CKD patients and 1.9% in normal controls (P < 0.001); and, 0.39% and 0.26% (P < 0.001) in advanced MD. Mild to moderate CKD patients had higher risk for MD [adjusted odds ratio (OR), 1.301; 95% confidence interval (CI), 1.200–1.411; P < 0.001] than normal renal function subjects. The association was more pronounced for advanced MD. From all age strata (10 years increase), the presence of CKD in those patients aged less than 40 years had highest OR for all MD (OR = 2.125, 95% CI: 1.417–3.186, P < 0.001). The results were consistent in interaction terms, highlighting the importance of CKD in young age patient for risk of MD. The high risk for MD in mild to moderate CKD patients remains significant after adjustment for personal habits (alcohol drinking and smoking, model 1; OR: 1.371; 95% CI: 1.265–1.486; P < 0.001), comorbidities (dyslipidemia, cerebrovascular disease, and peripheral vascular disease, model 2; OR: 1.369; 95% CI: 1.264–1.484; P < 0.001) and all these factors (model 3; OR: 1.320, 95% CI: 1.218–1.431, P < 0.001). This association was consistent in the subanalysis, excluding those patients with diabetic retinopathy. Proper diagnosis and timely intervention should be warranted to retard visual loss of these patients.

Subretinal Transplantation of Embryonic Stem Cell-Derived Retinal Pigment Epithelium for the Treatment of Macular Degeneration: An Assessment at 4 Years.

Advanced macular degeneration is an important cause of vision loss in the United States with over 2 million people affected by the disease. Despite substantial progress in the development of new therapies for wet AMD, the severe visual impairment associated with geographic atrophy in dry AMD or Stargardt disease remains untreatable. Recently, two phase I/II studies involving 18 patients with these diseases have demonstrated that it is possible to safely implant human embryonic stem cell-derived RPE (hESC-RPE) in an attempt to rescue photoreceptors and visual function. The anatomical and functional results are encouraging, with more than half of treated patients experiencing sustained improvements in visual acuity and demonstrating evidence of possible cellular engraftment. However, any conclusions remain tempered by the relatively short follow-up time, lack of a formal control group, poor initial visual acuity, and small number of patients. Aside from an instance of postoperative infectious endophthalmitis, no adverse events related to the cell therapy, such as hyperproliferation, tumorigenicity, or rejection-related inflammation were noted in this initial cohort of 18 patients. These first-in-human safety studies have opened the door to future studies enrolling patients with less advanced disease, treating other diseases that result in RPE loss, employing shorter immunosuppressive regimens, and using alternative strategies for RPE transplantation such as sheets of cells with or without scaffolding to mimic Bruch's membrane. The ultimate goal of these initial safety studies is to promote continued translation of complex biological therapies into meaningful treatment strategies that may address unmet medical needs.

Anxiety and depression in patients with advanced macular degeneration: current perspectives.

Age-related macular degeneration (AMD) – despite advances in prevention and medical treatment options – remains prevalent among older adults, often resulting in functional losses that negatively affect the mental health of older adults. In particular, the prevalence of both anxiety and depression in patients with AMD is high. Along with medical treatment options, low vision rehabilitation and AMD-specific behavioral and self-management programs have been developed and have demonstrated effectiveness in improving the mental health of AMD patients. This article reviews the prevalence of anxiety and depression in patients with advanced AMD, discusses potential mechanisms accounting for the development of depression and anxiety in AMD patients, presents the state-of the-art of available interventions for addressing anxiety and depression in AMD patients, and delineates recommendations for eye care professionals regarding how to screen for these two prevalent mental health problems and how to facilitate appropriate treatment for patients with AMD.

Adherence to a Mediterranean diet, genetic susceptibility, and progression to advanced macular degeneration: a prospective cohort study

Adherence to a Mediterranean-type diet is linked to a lower risk of mortality and chronic disease, but the association with the progression of age-related macular degeneration (AMD) and genetic susceptibility is unknown. We examined the association of adherence to the Mediterranean diet and genetic susceptibility with progression to advanced AMD. Among 2525 subjects in the AREDS (Age-Related Eye Disease Study), 1028 eyes progressed to advanced AMD over 13 y. Baseline data for demographic and behavioral covariates were collected by using questionnaires. Dietary data were collected from food-frequency questionnaires. The alternate Mediterranean diet (aMeDi) score (range: 0-9) was constructed from individual intakes of vegetables, fruit, legumes, whole grains, nuts, fish, red and processed meats, alcohol, and the ratio of monounsaturated to saturated fats. Ten genetic loci in 7 genes [complement factor H (CFH), age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase 1 (ARMS2/HTRA1), complement component 2 (C2), complement factor B (CFB), complement component 3 (C3), collagen type VIII α 1 (COL8A1), and RAD51 paralog B (RAD51B)] were examined. Survival analysis was used to assess individual eyes for associations between incident AMD and aMeDi score, as well as interaction effects between aMeDi score and genetic variation on risk of AMD. A high aMeDi score (score of 6-9) was significantly associated with a reduced risk of progression to advanced AMD after adjustment for demographic, behavioral, ocular, and genetic covariates (HR: 0.74; 95% CI: 0.61, 0.91; P-trend = 0.007). The aMeDi score was significantly associated with a lower risk of incident advanced AMD among subjects carrying the CFH Y402H nonrisk (T) allele (P-trend = 0.0004, P-interaction = 0.04). The aMeDi score was not associated with AMD among subjects who were homozygous for the risk (C) allele. Higher adherence to a Mediterranean diet was associated with reduced risk of progression to advanced AMD, which may be modified by genetic susceptibility. This trial was registered at clinicaltrials.gov as NCT00594672.

New add-on intraocular lens for patients with age-related macular degeneration

We present a new option for visual rehabilitation of patients with advanced macular degeneration and evaluate the outcomes in the first 8 patients who had implantation of the ciliary sulcus-fixated macular add-on intraocular lens (IOL) (Scharioth Macula Lens) at our institute. The surgical technique for implantation of the add-on IOL is described. Near vision improved in 7 eyes and was stable in 1 eye. The corrected near visual acuity improved by 4.4 lines with the macular add-on IOL at 15 cm versus with glasses at 40 cm; it improved by 2.1 lines with the macular add-on IOL at 15 cm versus with glasses at 15 cm. Distance vision was stable in all eyes. No intraoperative or postoperative complication occurred. The macular add-on IOL has the potential of improving near vision and reading ability in patients with advanced age-related macular degeneration. Dr. Scharioth is a consultant to Alcon Laboratories, Inc., and Medicontur Ltd. He is the inventor of the Scharioth Macula Lens and receives royalties.

Three New Genetic Loci (R1210C in CFH, Variants in COL8A1 and RAD51B) Are Independently Related to Progression to Advanced Macular Degeneration

ObjectivesTo assess the independent impact of new genetic variants on conversion to advanced stages of AMD, controlling for established risk factors, and to determine the contribution of genes in predictive models.MethodsIn this prospective longitudinal study of 2765 individuals, 777 subjects progressed to neovascular disease (NV) or geographic atrophy (GA) in either eye over 12 years. Recently reported genetic loci were assessed for their independent effects on incident advanced AMD after controlling for 6 established loci in 5 genes, and demographic, behavioral, and macular characteristics. New variants which remained significantly related to progression were then added to a final multivariate model to assess their independent effects. The contribution of genes to risk models was assessed using reclassification tables by determining risk within cross-classified quintiles for alternative models.ResultsThree new genetic variants were significantly related to progression: rare variant R1210C in CFH (hazard ratio (HR) 2.5, 95% confidence interval [CI] 1.2–5.3, P = 0.01), and common variants in genes COL8A1 (HR 2.0, 95% CI 1.1–3.5, P = 0.02) and RAD51B (HR 0.8, 95% CI 0.60–0.97, P = 0.03). The area under the curve statistic (AUC) was significantly higher for the 9 gene model (.884) vs the 0 gene model (.873), P = .01. AUC’s for the 9 vs 6 gene models were not significantly different, but reclassification analyses indicated significant added information for more genes, with adjusted odds ratios (OR) for progression within 5 years per one quintile increase in risk score of 2.7, P<0.001 for the 9 vs 6 loci model, and OR 3.5, P<0.001 for the 9 vs. 0 gene model. Similar results were seen for NV and GA.ConclusionsRare variant CFH R1210C and common variants in COL8A1 and RAD51B plus six genes in previous models contribute additional predictive information for advanced AMD beyond macular and behavioral phenotypes.

Validation of a Prediction Algorithm for Progression to Advanced Macular Degeneration Subtypes

Risk score models predicting the progression of age-related macular degeneration (AMD) to its advanced forms may be useful for targeting high-risk individuals for lifestyle changes that reduce risk for AMD progression, helping with differential diagnosis of AMD and its subtypes, identifying high-risk subjects for participation in clinical trials, and selecting appropriate therapies. To develop and validate a predictive model for progression to advanced stages of AMD in 2 independent cohorts. DESIGN Participants in a validation cohort and an independent derivation population were classified into 5 stages of AMD based on ocular examination and fundus photographs at baseline. Progression was defined as either eye progressing from stage 1, 2, or 3 to either stage 4 or stage 5 at any follow-up visit to the end of the study. Cox proportional hazards models were used for progression analyses. Covariates included demographic and environmental factors, 6 variants in 5 genes, and baseline AMD grades in both eyes. The algorithm developed with the derivation sample was assessed for calibration and discrimination in the validation data set. Clinic populations and referrals. The derivation population comprised 2914 subjects with 809 progressors. The independent validation cohort comprised 980 individuals with no, early, or intermediate AMD in at least one eye at baseline, of whom 294 progressed to advanced stages of geographic atrophy or neovascular disease. Progression to advanced AMD. RESULTS For the model with all nongenetic and genetic factors, the respective C statistics for progression to advanced AMD in the derivation and validation samples were 0.858 and 0.750 at 5 years and 0.884 and 0.809 at 10 years, and models also discriminated risk for progression to geographic atrophy and neovascular disease separately. For unilateral or bilateral intermediate AMD, 5-year cumulative incidence rates of progression to advanced AMD were 10% with the low-risk score and 50% with the high-risk score; for unilateral advanced disease, the progression rates were 22% and 80% for the fellow eye. The risk prediction model was validated in an independent study of progression from no, early, or intermediate stages to advanced subtypes of AMD and will be useful for research, clinical trials, and personalized medicine.

Severity Staging by Early Features of Age-Related Maculopathy Exhibits Weak Relationships with Functional Deficits on SWS Grating Acuity

To examine the relationship between short-wavelength-sensitive (SWS) resolution acuity and epidemiologically defined stages of early age-related maculopathy (ARM). Subjects consisted of 88 adults aged 51 to 87 years. Psychophysical testing was undertaken in only one eye of each subject (the study eye). All study eyes had a LogMAR acuity of 0.30 (20/40 Snellen) or better. SWS and achromatic grating resolution acuity were measured at 6 degrees eccentricity from the fovea. Stereoscopic color fundus photographs centered on the macula were taken on both eyes of each subject and were graded using the Wisconsin Age-Related Maculopathy Grading System (WARMGS). After grading, features of ARM were combined to assign a severity stage from 0 to 5 using the methods described by the Rotterdam Eye Study. Relationships between visual function, study eye ARM stage, and fellow eye status were examined with the use of standard statistical analysis. Although SWS resolution acuity was significantly reduced in eyes classified as having any ARM compared with eyes classified as having no ARM (P = 0.002), there was no relationship between the severity of functional deficits and the morphologic severity from stage 1 to stage 4. On reassigning subject eyes to a revised severity staging (stage 0, stages 1 to 4 combined, and stage 5), SWS acuity was significantly different among these three groups (P < 0.001). No significant relationship was found between achromatic resolution acuity and ARM staging. The status of the fellow eye (advanced macular degeneration present or absent) was not significantly related to visual function in the study eye. Significant functional deficits in SWS resolution acuity were found in eyes with ARM features, but the severity of functional loss did not correlate well with the currently accepted method of assigning a morphologic severity stage. Longitudinal studies may reveal further information on the relationships between functional deficits, ARM status, disease progression, and outcome.

Micropulse laser treatment of retinal–choroidal anastomoses in age-related macular degeneration

Retinal-choroidal anastomoses (RCA) are a common finding in advanced cases of age-related macular degeneration. These high-flow lesions are associated with extensive subretinal exudation. This study examines the role of high-energy, short-duration (micropulse) laser pulses in effectively closing these shunts and reducing subretinal fluid. Nineteen consecutive eyes with advanced age-related macular degeneration undergoing treatment of RCAs to reduce subretinal exudation in a referral-only retina practice were reviewed retrospectively. RCA were identified using high-speed indocyanine green angiography. RCA were closed using a high-energy, short-duration laser pulse technique. Outcome measures included visual acuity, resolution of subretinal fluid and persistence of RCA. Nineteen eyes with RCA associated with macular degeneration were successfully treated. Mean baseline visual acuity was 20/140 (HM to 20/50). One hundred percent of eyes had subretinal exudation and 73% had subretinal fibrosis at the time initial treatment. At mean follow-up of 11.7 (2-23) months, patients had undergone an average of 3.52 (1-12) sessions of laser treatment. Average final visual acuity was 20/146 (CF to 20/40). Fifty-three percent of eyes had complete resolution of subretinal fluid. One hundred percent had subretinal fibrosis. Forty-three percent had complete closure of RCA. No significant complications were encountered. High-energy, short-duration laser appears to be a reproducible technique to obtain closure of RCA associated with advanced macular degeneration. It appears to be effective in reducing subretinal exudation associated with these lesions. The technique is associated with stabilization of visual acuity without significant risk of complication.

X-Linked Recessive Atrophic Macular Degeneration from RPGR Mutation

We mapped a new X-linked recessive atrophic macular degeneration locus to Xp21.1–p11.4 and show allelic involvement of the gene RPGR, which normally causes severe peripheral retinal degeneration leading to global blindness. Ten affected males whom we examined had primarily macular atrophy causing progressive loss of visual acuity with minimal peripheral visual impairment. One additional male showed extensive macular degeneration plus peripheral loss of retinal pigment epithelium and choriocapillaries. Full-field electroretinograms (ERGs) showed normal cone and rod responses in some affected males despite advanced macular degeneration, emphasizing the dissociation of atrophic macular degeneration from generalized cone degenerations, including X-linked cone dystrophy (COD1). The RPGR gene nonsense mutation G→T at open reading frame (ORF)15+1164 cosegregated with the disease and may create a donor splice site. Identification of an RPGR mutation in atrophic maculardegeneration expands the phenotypic range associated with this gene and provides a new tool for the dissection of the relationship between clinically different retinal pathologies.

Depression, visual acuity, comorbidity, and disability associated with age-related macular degeneration

Objective To examine (1) the prevalence of depressive disorders in community-dwelling adults with advanced age-related macular degeneration (AMD) and (2) the relationship in this population between depression, visual acuity, the number of comorbid medical conditions, disability caused by vision loss as measured by the National Eye Institute-Vision Function Questionnaire (NEI-VFQ) and the vision-specific Sickness Impact Profile (SIPV), and disability caused by overall health status as measured by the Sickness Impact Profile-68 (SIP). Design Analysis of cross-sectional baseline data from a randomized clinical trial. Participants Participants were 151 adults aged 60 and older (mean age, 80 years) with advanced macular degeneration whose vision was 20/60 or worse in their better eye. Methods Subjects were interviewed using measures of depression, disability, and chronic medical conditions. Visual acuity was obtained. Nonparametric correlation analyses and linear regression analyses were performed. Main outcome measures Structured Clinical Interview for DSM-IV (SCID-IV), Geriatric Depression Scale (GDS), NEI-VFQ, SIPV, and SIP. Results Of the participants, 32.5% (n = 49) met SCID-IV criteria for depressive disorder, twice the rate observed in previous studies of community-dwelling elderly. Over and above depression (GDS), visual acuity aided in prediction of the level of vision-specific disability (NEI-VFQ and SIPV). Conclusions Depressive disorder is a significant problem for the elderly afflicted with advanced macular degeneration. Further research on psychopharmacologic and psychotherapeutic interventions for depressed AMD patients is warranted to improve depression and enhance functioning. Over and above depression, visual acuity aided in predicting vision-specific disability. Treatment strategies that teach patients to cope with vision loss should be developed and evaluated.

Rehabilitation of the visually handicapped with advanced macular degeneration. A follow-up study at the Low Vision Clinic, Department of Ophthalmology, University of Linköping.

Hundred-and-twenty patients with advanced macular degeneration (senile, disciform, and hereditary forms), which could not be helped in a satisfactory way by simple magnifying aids, were studied for an average of 5 years (a minimum of 3 years), during which they had access to a full range of low vision rehabilitation measures including advanced optical aids and educational methods for training in the use of these aids and in the utilization of residual vision. The mean age of the patients was 72 years. They were all in a mental condition enabling them to understand and follow instructions. Just over half the patients were obliged to learn from the outset how to utilize peripheral retina, i.e. through eccentric viewing, high magnification low vision aids and very short reading distances, a mean of 4.4 cm, which demand specially qualified educational methods for low vision training. (A second group of 198 patients with macular degeneration was handled by the optician alone because either macular degeneration was moderate and the patients could manage with simple optical aids, or the patients were in such a bad mental condition, obvious already from the referral documents, that they were unable to use sophisticated aids in spite of the fact that they would have needed them with regard to their poor vision.) Telescopes were the most frequent aid used for distance, having a mean magnification of 4.6 X. Among the aids for reading, the most common were increased near additions and hyperocular lenses, having a mean power of 22.6 dioptres (magnification 5.7 X). Aids were also furnished for intermediate distance and for 'spot use'. The mean number of series of visits was 2.5 and the number of training sessions (1 h) per series of visits was 3.0. Mean visual acuity improved from 0.18 to 0.64 with aids and training on the first series of visits, and reached 0.53 by the last series. The number of patients able to read TV titles increased from 6.7% to 57.5% and was 49.2% after the last series of visits. The number of individuals able to read newspaper text increased from 0.8% to 92.5%. After the last series of visits, the number was still as high as 80.0%. The results show that the presented methods for rehabilitation of patients with macular degeneration through optical aids and educational methods for training in the utilization of these aids and of residual vision are outstandingly successful. The use of the individual's vision and his situation in life often improve dramatically.(ABSTRACT TRUNCATED AT 400 WORDS)