Treatment contentment and preference of patients undergoing intravitreal anti-VEGF therapy.

PURPOSE: The aim of this study is to investigate patients´ treatment preference between the pro re nata (PRN) and treat and extend (T&E) regimens and their feelings and contentment undergoing intravitreal injections (IVI) with anti-vascular endothelial growth factor (anti-VEGF) agents. METHODS: Six months after the switch of the treatment regimen from PRN to T&E, answers of a 16-item questionnaire of 105 patients under IVI therapy regarding age, sex and treatment preference (T&E or PRN regimen), as well as burden and anxiety resulting from therapy, were evaluated. Analysis of associations between answers of the questionnaire was executed using Pearson's Chi2 test and Mann-Whitney U test. P values ≤ 0.05 were considered statistically significant. RESULTS: Nearly all patients (90.5%) felt well informed about disease and therapy. Comparing treatment regimen, 13.7% thought PRN was better and 23.3% felt T&E was better. The majority considered PRN and T&E to be equal (60.3%). No significant association between treatment regimen and age (p = 0.15), gender (p = 0.35) and duration of IVI therapy (p = 0.42) was seen. The examination results are associated with fear in the majority of patients (53.3%). Fear about the IVI was indicated by 47.6% of individuals and was significantly associated with pain during treatment (p = 0.0003), pain after treatment (p = 0.004) and fear about unfavourable examination results regarding disease activity (p = 7.94 × 10-7). CONCLUSIONS: Most patients are satisfied with the IVI therapy and the treatment regimen. Fear of the IVI and particularly of unfavourable examination results demonstrate the high treatment burden for patients undergoing anti-VEGF therapy. These aspects should be taken into account by healthcare professionals.

Volumetric Analysis and Clinical Outcome in 54 Patients with Retrobulbar Hematoma.

PURPOSE: Retrobulbar hematoma (RBH) is a rare but serious vision threatening emergency. We analyze the relationship between hematoma volume, visual impairment and outcome. METHODS: Fifty-four patients with RBH receiving orbital decompression were retrospectively included. Volumetric analysis of RBH was performed by semi-automatic segmentation based on preoperative CT scans using ITK-SNAP software. Best corrected visual acuity (BCVA) measurements were obtained and correlated in 2 groups (no light perception (NLP), severe visual impairment) with the hematoma volume. RESULTS: NLP was documented preoperatively in 5/28 and postoperatively in 9/43 patients. Preoperative NLP was significantly associated with a larger hematoma volume (P = .03) and higher hematoma/orbital volume ratio (P = .03). Postoperative severe visual impairment showed significant associations with a larger hematoma volume (P = .02) as well as higher hematoma/orbital volume ratio (P = .02). CONCLUSION: Eyes with severe visual impairment and large hematoma volumes preoperatively are at high risk of permanent vision loss. Hematoma volume calculation might represent an additional prognostic parameter for visual outcome after RBH.

Genetic and environmental risk factors for reticular pseudodrusen in the EUGENDA study.

PURPOSE: The purpose of this study was to analyze genetic and nongenetic associations with reticular pseudodrusen (RPD) in patients with and without age-related macular degeneration (AMD). METHODS: This case-control study included 2,719 consecutive subjects from the prospective multicenter European Genetic Database (EUGENDA). Color fundus photographs and optical coherence tomography (OCT) scans were evaluated for the presence of AMD and RPD. Association of RPD with 39 known AMD polymorphisms and various nongenetic risk factors was evaluated. Stepwise backward variable selection via generalized linear models (GLMs) was performed based on models including the following: a) age, sex, and genetic factors and b) all predictors. Receiver operating characteristic (ROC) curves and the areas under the curve (AUCs) were determined. RESULTS: RPD were present in 262 cases (no AMD, n = 9 [0.7%; early/intermediate AMD, n = 75 [12.4%]; late AMD, n = 178 [23.8%]). ROC analysis of the genetic model including age, APOE rs2075650, ARMS2 rs10490924, CFH rs800292, CFH rs12144939, CFI rs10033900, COL8A1 rs13081855, COL10A1 rs3812111, GLI3 rs2049622, and SKIV2L rs4296082 revealed an AUC of 0.871. Considering all possible predictors, backward selection revealed a slightly different set of genetic factors, as well as the following nongenetic risk factors: smoking, rheumatoid arthritis, steroids, antiglaucomatous drugs, and past sunlight exposure; the results showed an AUC of 0.886. CONCLUSIONS: RPD share a variety of genetic and nongenetic risk factors with AMD. Future AMD grading systems should integrate RPD as an important risk phenotype.

[Retinal Detachment Part 2 - Treatment Strategies]. / Netzhautablösung ­ Teil 2.

This review article summarizes the relevant surgical strategies for retinal detachment repair and discusses common postoperative complications, as well as factors influencing the functional and anatomical results. Treatment of retinal detachment requires surgery. In most cases, pars plana vitrectomy is performed. In phakic patients with a clear lens scleral buckling can be considered as an alternative. Laser and cryotherapy are still the standard for treatment in symptomatic retinal tears or degenerations without retinal detachment. Postoperatively, the occurrence of a re-detachment as well as the development of proliferative vitreoretinopathy can have a negative influence on postoperative results. Furthermore, typical complications include the occurrence of a cystoid macular edema, epiretinal membrane or even persistent neurosensory detachment. Functional results are significantly influenced by macular involvement and the primary anatomical success rate.

The Effect of Genetic Variants Associated With Age-Related Macular Degeneration Varies With Age.

Purpose: The prevalence of age-related macular degeneration (AMD) increases dramatically with age. This large collaborative study investigates the effects of 51 late-AMD-associated genetic variants in different ages, focusing on individuals above the age of 90 years. Methods: The study included 27,996 individuals of the International AMD Genomics Consortium; 14,539 showed late AMD (51.9%) and 13,457 were controls (48.1%). Four age groups were compiled: 60 to 69 years, n = 6514, AMD = 2210 (33.9%); 70 to 79 years, n = 12228, AMD = 6217 (51.7%); 80 to 89 years, n = 8285, AMD = 5326 (64.3%); and ≥90 years, n = 969, AMD = 686 (70.8%). The effect sizes of 51 AMD-associated genetic variants were calculated for all age groups and were compared among the age groups. Results: Six variants were associated with late AMD in individuals ≥ 90 years of age (P ≤ 0.0006). For rs10922109 and rs570618 (both in CFH), the minor allele (MA) was protective, and minor allele frequency (MAF) increased with age in cases and controls. For rs116503776 in C2/CFB/SKIV2L, the MA was protective, and MAF increased in cases. For rs3750846 in ARMS2/HTRA1, the MA increased risk, and MAF was lower in cases with increasing age. For rs6565597 in NPLOC4/TSPAN10, the MA increased risk. For rs5754227 in SYN3/TIMP3, the MA was protective, and there was no consistent variation in MAF with age. Variants in CFH and ARMS2 showed lower effect sizes at greater age. Interaction analysis showed strong age-related effects for rs570618 (P = 2.24 × 10-7) and rs3750846 (P = 0.001). Total genetic risk was lower in individuals ≥ 90 years old (area under the curve [AUC], 0.795) than in those 70 to 79 years old (AUC, 0.831; P = 0.03). Conclusions: Effect sizes and MAF of genetic risk factors for late AMD differed among the age groups. These results could guide future work on AMD risk assessment in older individuals.

[Retinal Detachment Part 1 - Epidemiology, Risk Factors, Clinical Characteristics, Diagnostic Approach]. / Netzhautablösung ­ Teil 1.

This review article gives an overview of the epidemiology, relevant risk factors, clinical characteristics and the diagnostic approach of rhegmatogenous retinal detachment. Rhegmatogenous retinal detachment is an ophthalmologic emergency needing immediate surgical treatment. Main risk factors are retinal tears, myopia and previous cataract surgery. For patients with symptoms of posterior vitreous detachment, indirect ophthalmoscopy under pupil dilatation is necessary to diagnose retinal tears or retinal detachment. Differential diagnoses are tractive or exudative forms of retinal detachment or retinoschisis.

Genetic and environmental risk factors for extramacular drusen.

PURPOSE: To analyze risk factors for extramacular drusen (EMD) in patients with age-related macular degeneration (AMD) and healthy control individuals. METHODS: This case-control study included 1,520 patients from the prospective multicenter European Genetic Database (EUGENDA). Color fundus photographs and optical coherence tomography scans were evaluated for the presence of AMD and EMD. EMD was considered present if ten or fewer drusen including at least one intermediate-sized drusen were detected outside the macula. Association of EMD was evaluated with various genetic and non-genetic risk factors (31 single nucleotide polymorphisms, systemic complement activation, smoking, cardiovascular factors, and sunlight exposure) using logistic regression models adjusted for age, gender, and AMD. RESULTS: EMD was found in 608 subjects (40%) and AMD in 763 (50%) of 1,520 participants. EMD was strongly associated with AMD (p = 2.83 × 10-63, odds ratio [OR] 7.63). After adjustment for AMD, age (p = 0.06, OR 1.02), female gender (p = 3.34 × 10-24, OR 4.44), history of sunlight exposure ≥ 8 h /day (p = 0.0004, OR 1.99), serum complement activation (p = 0.004, OR 1.61), and polymorphisms in ARMS2 (p = 0.00016, OR 1.43) and CFI (p = 0.043, OR 1.20) were identified as risk factors for EMD. The final prediction model including these variants showed an area under the curve of 0.820. CONCLUSIONS: The comprehensive analysis of various risk factors revealed a common genetic and pathological pathway of EMD with AMD. Future longitudinal studies are needed to evaluate the role of EMD in otherwise healthy subjects as an expanded phenotype of AMD.

Complement Activation Levels Are Related to Disease Stage in AMD.

Purpose: To study the levels of complement activation in different disease stages of AMD and the influence of genetic polymorphisms in complement genes. Methods: We included 797 patients with AMD and 945 controls from the European Genetic Database. Patients were grouped into five AMD stages: early AMD, intermediate AMD, central geographic atrophy, active choroidal neovascularization or inactive choroidal neovascularization. Differences in complement activation, as defined by the systemic C3d/C3 ratio, between AMD stages were evaluated using general linear modeling. In addition, we evaluated the influence of 18 genetic AMD polymorphisms in complement genes and their effect on complement activation. Differences in complement activation between stages were evaluated stratifying by complement associated haplotypes. Results: Complement activation levels differed significantly between AMD disease stages. As compared with controls, the C3d/C3 ratio was higher in patients with intermediate AMD (P < 0.001) and central geographic atrophy (P = 0.001). Two polymorphisms in CFH (rs10922109 and rs570618) and one in CFB (rs116503776) were significantly associated with complement activation. The association between AMD disease stage and complement activation was more pronounced in patients with haplotypes associated with the highest complement activation. Conclusions: In general, consecutive AMD disease stages showed increasing levels of complement activation, especially in individuals with a genetic burden in complement genes. These findings contribute to the discussion on the pathogenesis of AMD in relation to complement activation and might suggest refinement in patient selection and the optimum window of treatment with complement inhibitors. Prospective studies are needed to confirm these results.

Major Predictive Factors for Progression of Early to Late Age-Related Macular Degeneration.

INTRODUCTION: We present a prediction model for progression from early/intermediate to advanced age-related macular degeneration (AMD) within 5.9 years. OBJECTIVES: To evaluate the combined role of genetic, nongenetic, and phenotypic risk factors for conversion from early to late AMD over ≥5 years. METHODS: Baseline phenotypic characteristics were evaluated based on color fundus photography, spectral-domain optical coherence tomography, and infrared images. Genotyping for 36 single-nucleotide polymorphisms as well as systemic lipid and complement measurements were performed. Multivariable backward logistic regression resulted in a final prediction model. RESULTS AND CONCLUSIONS: During a mean of 5.9 years of follow-up, 22.4% (n = 52) of the patients (n = 232) showed progression to late AMD. The multivariable prediction model included age, CFH variant rs1061170, pigment abnormalities, drusenoid pigment epithelial detachment (DPED), and hyperreflective foci (HRF). The model showed an area under the curve of 0.969 (95% confidence interval 0.948-0.990) and adequate calibration (Hosmer-Lemeshow test, p = 0.797). In addition to advanced age and carrying a CFH variant, pigment abnormalities, DPED, and HRF are relevant imaging biomarkers for conversion to late AMD. In clinical routine, an intensified monitoring of patients with a high-risk phenotypic profile may be suitable for the early detection of conversion to late AMD.

ORCA study: real-world versus reading centre assessment of disease activity of neovascular age-related macular degeneration (nAMD).

BACKGROUND/AIMS: The prospective, non-interventional ORCA module of the OCEAN study (Observation of Treatment Patterns with Lucentis in Approved Indications) evaluated the qualiy of spectral domain-optical coherence tomography (SD-OCT) image interpretation and treatment decisions by clinicians in Germany and the impact on visual outcomes over 24 months in patients with neovascular age-related macular degeneration (nAMD). METHODS: 2286 SD-OCT scans of 205 eyes were independently evaluated by clinicians and reading centres (RCs) regarding signs of choroidal neovascularisation (CNV) activity, including presence of intraretinal fluid, subretinal fluid, and/or increase in pigment epithelial detachments. Agreement between clinicians and RCs was calculated. Treatment decisions by clinicians and the impact on treatment outcomes were evaluated. RESULTS: CNV activity was detected by RCs on 1578 scans (69.0%) and by clinicians on 1392 scans (60.9%), with agreement in 74.9% of cases. Of the 1578 scans with RC detected CNV activity, anti-vascular endothelial growth factor injections were performed by clinicians in only 35.5% (560/1578). In 19.7% of cases (311/1578), lack of treatment was justified by patients request, termination criteria or chronic cystoid spaces without other signs for CNV activity. In 44.8% of cases (707/1578) with RC detected CNV activity, clinicians claimed no treatment was necessary despite having correctly detected CNV activity in about 2/3 of these cases. In 34% of cases with presumed undertreatment, visual acuity declined in the following visit. CONCLUSION: Although broad agreement on CNV activity parameters was observed between clinicians and RCs, correct identification of CNV activity did not always lead to the initiation of (re-)treatment. To preserve vision over time, correct interpretation of SD-OCT scans and careful retreatment decisions are required. TRIAL REGISTRATION NUMBER: NCT02194803.

[Baseline diagnostics and initial treatment decision for anti-vascular endothelial growth factor treatment in retinal diseases : Comparison between results by study physician and reading centers (ORCA/OCEAN study)]. / Initiale Diagnostik und Indikationsstellung zur Anti-Vascular-Endothelial Growth-Factor-Therapie bei Netzhauterkrankungen : Vergleich der Befundung durch Studienarzt versus Reading Center (ORCA/OCEAN-Studie).

BACKGROUND: The ORCA module of the non-interventional OCEAN study investigated the use of retinal imaging diagnostics in the clinical treatment of patients undergoing vascular endothelial growth factor (VEGF) inhibitor treatment as part of routine clinical care. This article analyzes the agreement between the diagnosis documented by the treating ophthalmologist and the evaluation of reading centers at baseline as well as the effect on the response to treatment during the course. METHODS: A total of 396 patients (age 75.4 years) were enrolled in which ranibizumab treatment was indicated by the treating ophthalmologist due to either diabetic macular edema (DME), neovascular age-related macular degeneration (nvAMD) or retinal venous occlusion (RVO). Over a period of 24 months, patient and examination data, treatments and interpretation of retinal imaging data by the treating ophthalmologist were systematically recorded. Furthermore, retinal imaging data were also evaluated by three reading centers. RESULTS: In 338 out of 396 (85.4%) study eyes, the baseline diagnosis of the treating ophthalmologist was confirmed by the reading centers (DME 87.5%, nvAMD 82.3%, RVO 94.9%). In 17 of the remaining 58 eyes with a discrepant diagnosis, there was at least a consensus with respect to the indications for VEGF inhibitor therapy. The differential diagnoses included a variety of different retinal diseases. During follow-up of up to 3 months, eyes with a consistent diagnosis showed a clear increase in visual acuity (6.4 versus 2.7 letters, p = 0.05) and greater decrease in central retinal thickness (-112.3 versus -24.4 µm, p < 0.0001). DISCUSSION: The initial treatment decision for anti-VEGF therapy with consideration of the differential diagnoses can be challenging. Accurate evaluation of the clinical and imaging findings along with appropriate expertise appear to be important. The observation of superior initial response in eyes with a consensus of the diagnosis at baseline underlines the relevance of an adequate initial assessment for a successful treatment outcome.

Evaluation of serum sphingolipids and the influence of genetic risk factors in age-related macular degeneration.

Sphingolipids are bioactive molecules associated with oxidative stress, inflammation, and neurodegenerative diseases, but poorly studied in the context of age-related macular degeneration (AMD), a prevalent sight-threatening disease of the ageing retina. Here, we found higher serum levels of hexosylceramide (HexCer) d18:1/16:0 in patients with choroidal neovascularization (CNV) and geographic atrophy (GA), two manifestations of late stage AMD, and higher ceramide (Cer) d18:1/16:0 levels in GA patients. A sensitivity analysis of genetic variants known to be associated with late stage AMD showed that rs1061170 (p.Y402H) in the complement factor H (CFH) gene influences the association of Cer d18:1/16:0 with GA. To understand the possible influence of this genetic variant on ceramide levels, we established a cell-based assay to test the modulation of genes in the ceramide metabolism by factor H-like protein 1 (FHL-1), an alternative splicing variant of CFH that also harbors the 402 residue. We first showed that malondialdehyde-acetaldehyde adducts, an oxidation product commonly found in AMD retinas, induces an increase in ceramide levels in WERI-Rb1 cells in accordance with an increased expression of ceramide synthesis genes. Then, we observed that cells exposed to the non-risk FHL-1:Y402, but not the risk associated variant FHL-1:H402 or full-length CFH, downregulated ceramide synthase 2 and ceramide glucosyltransferase gene expression. Together, our findings show that serum ceramide and hexosylceramide species are altered in AMD patients and that ceramide levels may be influenced by AMD associated risk variants.

Whole-Exome Sequencing in Age-Related Macular Degeneration Identifies Rare Variants in COL8A1, a Component of Bruch's Membrane.

PURPOSE: Genome-wide association studies and targeted sequencing studies of candidate genes have identified common and rare variants that are associated with age-related macular degeneration (AMD). Whole-exome sequencing (WES) studies allow a more comprehensive analysis of rare coding variants across all genes of the genome and will contribute to a better understanding of the underlying disease mechanisms. To date, the number of WES studies in AMD case-control cohorts remains scarce and sample sizes are limited. To scrutinize the role of rare protein-altering variants in AMD cause, we performed the largest WES study in AMD to date in a large European cohort consisting of 1125 AMD patients and 1361 control participants. DESIGN: Genome-wide case-control association study of WES data. PARTICIPANTS: One thousand one hundred twenty-five AMD patients and 1361 control participants. METHODS: A single variant association test of WES data was performed to detect variants that are associated individually with AMD. The cumulative effect of multiple rare variants with 1 gene was analyzed using a gene-based CMC burden test. Immunohistochemistry was performed to determine the localization of the Col8a1 protein in mouse eyes. MAIN OUTCOME MEASURES: Genetic variants associated with AMD. RESULTS: We detected significantly more rare protein-altering variants in the COL8A1 gene in patients (22/2250 alleles [1.0%]) than in control participants (11/2722 alleles [0.4%]; P = 7.07×10-5). The association of rare variants in the COL8A1 gene is independent of the common intergenic variant (rs140647181) near the COL8A1 gene previously associated with AMD. We demonstrated that the Col8a1 protein localizes at Bruch's membrane. CONCLUSIONS: This study supported a role for protein-altering variants in the COL8A1 gene in AMD pathogenesis. We demonstrated the presence of Col8a1 in Bruch's membrane, further supporting the role of COL8A1 variants in AMD pathogenesis. Protein-altering variants in COL8A1 may alter the integrity of Bruch's membrane, contributing to the accumulation of drusen and the development of AMD.

Genome-Wide Association Study Reveals Variants in CFH and CFHR4 Associated with Systemic Complement Activation: Implications in Age-Related Macular Degeneration.

PURPOSE: To identify genetic variants associated with complement activation, which may help to select age-related macular degeneration (AMD) patients for complement-inhibiting therapies. DESIGN: Genome-wide association study (GWAS) followed by replication and meta-analysis. PARTICIPANTS: AMD patients and controls (n = 2245). METHODS: A GWAS on serum C3d-to-C3 ratio was performed in 1548 AMD patients and controls. For replication and meta-analysis, 697 additional individuals were genotyped. A model for complement activation including genetic and non-genetic factors was built, and the variance explained was estimated. Haplotype analysis was performed for 8 SNPs across the CFH/CFHR locus. Association with AMD was performed for the variants and haplotypes found to influence complement activation. MAIN OUTCOME MEASURES: Normalized C3d/C3 ratio as a measure of systemic complement activation. RESULTS: Complement activation was associated independently with rs3753396 located in CFH (Pdiscovery = 1.09 × 10-15; Pmeta = 3.66 × 10-21; ß = 0.141; standard error [SE] = 0.015) and rs6685931 located in CFHR4 (Pdiscovery = 8.18 × 10-7; Pmeta = 6.32 × 10-8; ß = 0.054; SE = 0.010). A model including age, AMD disease status, body mass index, triglycerides, rs3753396, rs6685931, and previously identified SNPs explained 18.7% of the variability in complement activation. Haplotype analysis revealed 3 haplotypes (H1-2 and H6 containing rs6685931 and H3 containing rs3753396) associated with complement activation. Haplotypes H3 and H6 conferred stronger effects on complement activation compared with the single variants (P = 2.53 × 10-14; ß = 0.183; SE = 0.024; and P = 4.28 × 10-4; ß = 0.144; SE = 0.041; respectively). Association analyses with AMD revealed that SNP rs6685931 and haplotype H1-2 containing rs6685931 were associated with a risk for AMD development, whereas SNP rs3753396 and haplotypes H3 and H6 were not. CONCLUSIONS: The SNP rs3753396 in CFH and SNP rs6685931 in CFHR4 are associated with systemic complement activation levels. The SNP rs6685931 in CFHR4 and its linked haplotype H1-2 also conferred a risk for AMD development, and therefore could be used to identify AMD patients who would benefit most from complement-inhibiting therapies.

Alteration of retinal layers in healthy subjects over 60 years of age until nonagenarians.

PURPOSE: To assess alterations of retinal layers in healthy subjects over 60 years old. METHODS: Retinal layers of 160 healthy subjects (aged 60-100 years) without any retinal pathology were imaged using spectral domain optical coherence tomography. Mean thickness of retinal nerve fiber layer, ganglion cell/inner plexiform layer (GCLIPL), inner nuclear layer, outer plexiform layer/outer nuclear layer, photoreceptor complex (PR) and retinal thickness (RT) were measured in a 3.45 mm grid. Correlations between age and layers were estimated and linear regression equations were calculated. Different age-groups (60-69, 70-79, 80-89 years and nonagenarians, each group with 40 participants) were compared. RESULTS: Significant age-thickness correlations were observed for GCLIPL (P<0.001, r=-0.394), PR (P<0.001, r=-0.370) and RT (P<0.001, r=-0.290). A comparison between age groups 60-69 years and nonagenarians showed no significant thickness alteration of retinal nerve fiber layer (21.80±2.18 µm vs 22.82±2.97 µm, P=0.163), inner nuclear layer (37.23±3.02 µm vs 36.01±3.24 µm, P=0.07) and outer plexiform layer/outer nuclear layer (104.95±6.56 µm vs 104.23±7.59 µm, P=0.567), while GCLIPL (83.35±7.35 µm vs 74.38±9.09 µm), PR (83.03±3.31 µm vs 79.34±2.09 µm) and RT (330.64±12.63 µm vs 316.83±18.35 µm) showed a significant decrease (P<0.001 for all). CONCLUSION: Our study provides normative data of alterations of retinal layers for persons aged 60 years to nonagenarians and indicates a continuous decrease of RT, PR, and GCLIPL. This data may be useful for clinical trials investigating macular diseases in older patients.

Physical Activity and Age-related Macular Degeneration: A Systematic Literature Review and Meta-analysis.

PURPOSE: To better understand the association, in a white population, of physical activity and age-related macular degeneration (AMD)-the main cause of irreversible severe vision loss in developed countries-given the suggestion that a healthy lifestyle may assist in delaying the onset and progression of AMD. DESIGN: Systematic review and meta-analysis. METHODS: Medline, EMBASE, and Google Scholar were systematically searched for studies up to May 2015. Reference lists of published articles were hand searched and study authors were contacted to provide additional data. Those in the lowest category of activity in each study were compared with all other participants to assess the association between physical activity and both early and late AMD using random-effects meta-analysis. RESULTS: Nine studies (subject age range 30-97 years) were included in the meta-analysis. Physical activity was found to have a protective association with both early AMD (8 studies, n = 38 112, odds ratio (OR) 0.92, 95% confidence interval [CI] 0.86-0.98) and late AMD (7 studies, n = 28 854, OR 0.59, 95% CI 0.49-0.72). CONCLUSIONS: Physical activity is associated with lower odds of early and late AMD in white populations. These findings have important implications, reinforcing the public health message of staying active throughout life. However, further longitudinal studies are required to confirm and further characterize a protective effect of physical activity on the onset and/or progression of AMD.

Effect of Symptom Duration until Surgery on First-Year Outcome in Pseudophakic Primary Rhegmatogenous Retinal Detachment.

PURPOSE: To investigate the effect of symptom duration in pseudophakic primary rhegmatogenous retinal detachment (RRD) with or without macular involvement on functional and anatomical outcome during first-year follow-up. PROCEDURES: Retrospective review of cases with pars plana vitrectomy for retinal detachment repair. Symptom duration, functional outcome, and redetachment rates were analyzed. Symptom duration was grouped (1-3, 4-7, 8-14, 15-30, >30 days) and correlated to outcome in the first year of follow-up. RESULTS: 371 macula-off and 230 macula-on RRDs could be included. In macula-off RRDs, longer symptom duration was associated with higher redetachment rates (10-21%; p = 0.032). Patients presenting symptoms for less than 8 days showed significantly lower rates than those with a longer symptom duration (p = 0.046). In macula-on RRDs, symptom duration and outcome were not associated (p > 0.6). CONCLUSIONS: In macula-off RRD, early reattachment surgery is necessary to lower the risk for retinal redetachment. The aim in macula-on RRD is to prevent conversion to a macula-off situation.

RISK OF MULTIPLE RECURRING RETINAL DETACHMENT AFTER PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT REPAIR.

PURPOSE: To evaluate functional and anatomical outcomes of patients with retinal redetachments (re-RD) after surgery for primary rhegmatogenous retinal detachment. METHODS: Medical records of eyes with re-RD after rhegmatogenous retinal detachment surgery between 1999 and 2014 at the Department of Ophthalmology, University of Cologne, Germany, were retrospectively evaluated. Data included preoperative and postoperative clinical findings, best-corrected visual acuity, presence and grade of proliferative vitreoretinopathy, surgical procedures, and complication rates. RESULTS: Three hundred and twenty-eight eyes of 2,457 developed a re-RD (13.3%). Of these 328 eyes, 242 eyes (73.8%) had only one re-RD, whereas 86 eyes (26.2%) had 2 or more re-RDs. Visible presence of proliferative vitreoretinopathy during first redetachment surgery increased risk of re-RD with relative risk ratio of 1.46 (P = 0.05). Best-corrected visual acuity deteriorated with every additional re-RD (P < 0.001). Two hundred and thirty-seven eyes received oil endotamponde at least once. In 91 cases, oil endotamponade was left for long-term until last follow-up. CONCLUSION: Multiple re-RD (≥2 re-RDs) is an infrequent complication after rhegmatogenous retinal detachment surgery. After a first re-RD occurred, risk for multiple re-RD doubles compared with the risk of a first redetachment. Mean functional outcome is unfavorable, whereas predictability remains nevertheless poor because of the wide range of interindividual postoperative best-corrected visual acuity.