CLINICAL AND STRUCTURAL IMPACT OF SUBMACULAR FLUID AFTER PNEUMATIC RETINOPEXY REPAIR FOR RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To assess the impact of submacular fluid (SMF) after pneumatic retinopexy for primary rhegmatogenous retinal detachment repair. METHODS: Retrospective review of consecutive patients treated with pneumatic retinopexy for primary rhegmatogenous retinal detachment repair. 387 eyes (374 patients) were included, of which 166 underwent optical coherence tomography imaging after successful pneumatic retinopexy. Foveal-centered optical coherence tomography scans were reviewed. RESULTS: SMF occurred in 59 eyes (35.5%) and was associated with macular detachment ( P ≤ 0.001) and phakic lens status ( P = 0.007). Submacular fluid resolved over an average of 9.39 months and was associated with worse preprocedure best-corrected visual acuity and delayed visual recovery. The mean final best-corrected visual acuity was 0.277 logarithm of the minimum angle of resolution (20/40) in eyes with SMF and 0.162 logarithm of the minimum angle of resolution (20/30) in those without SMF ( P < 0.001). Submacular fluid was associated with discontinuity of the interdigitation zone ( P = 0.003), ellipsoid zone ( P = 0.005), and external limiting membrane ( P ≤ 0.001) after SMF resolution. Ellipsoid zone discontinuity was associated with worse visual prognosis ( P = 0.009). CONCLUSION: Trace SMF detected by optical coherence tomography is common after successful pneumatic retinopexy and resulted in delayed visual recovery and increased rates of outer retinal discontinuity after SMF resorption, although the final difference in best-corrected visual acuity in those with and without SMF was minimal.

Radiological protocol in spinal trauma: literature review and Spinal Cord Society position statement.

PURPOSE: The Spinal Cord Society constituted a panel tasked with reviewing the literature on the radiological evaluation of spinal trauma with or without spinal cord injury and recommend a protocol. This position statement provides recommendations for the use of each modality, i.e., radiographs (X-rays), computed tomography (CT), magnetic resonance imaging (MRI), as well as vascular imaging, and makes suggestions on identifying or clearing spinal injury in trauma patients. METHODS: PubMed was searched for the corresponding keywords from January 1, 1980, to August 1, 2017. A MEDLINE search was subsequently undertaken after applying MeSH filters. Appropriate cross-references were retrieved. Out of the 545 articles retrieved, 105 relevant papers that address the present topic were studied and the extracted content was circulated for further discussions. A draft position statement was compiled and circulated among the panel members via e-mail. The draft was modified by incorporating relevant suggestions to reach a consensus. RESULTS AND CONCLUSION: For imaging cervical and thoracolumbar spine trauma patients, CT without contrast is generally considered to be the initial line of imaging and radiographs are required if CT is unavailable or unaffordable. CT screening in polytrauma cases is best done with a multidetector CT by utilizing the reformatted images obtained when scanning the chest, abdomen, and pelvis (CT-CAP). MRI is indicated in cases with neurological involvement and advanced cervical degenerative changes and to determine the extent of soft tissue injury, i.e., disco-ligamentous injuries as well as epidural space compromise. MRI is also usually performed when X-rays and CT are unable to correlate with patient symptomatology. These slides can be retrieved under Electronic Supplementary Material.

Idiopathic Acute Exudative Polymorphous Vitelliform Maculopathy: Clinical Spectrum and Multimodal Imaging Characteristics.

PURPOSE: To describe clinical findings in patients with acute exudative polymorphous vitelliform maculopathy (AEPVM). DESIGN: Retrospective, observational, multicenter case series review. PARTICIPANTS: Consecutive patients diagnosed with idiopathic AEPVM. METHODS: Review of clinical charts, multimodal imaging, electrophysiologic findings, and genetic findings in previously unpublished patients and review of the literature. MAIN OUTCOME MEASURES: Clinical features of idiopathic AEPVM and differential diagnosis. RESULTS: Eighteen patients (age range, 21-74 years) with typical features of AEPVM, including initial localized, serous detachments followed by the development of characteristic yellow-white deposits in the vitelliform space. Over time, this hyperautofluorescent material gravitated within the larger lesions, resulting in typical curvilinear deposits characteristic of later stages. Symptoms and clinical findings lasted from weeks to several years. Some patients showed previously undescribed features such as fluorescein-negative intraretinal cystic changes, choroidal neovascularization, serous retinal elevations mimicking retinal folds, increased choroidal thickness, lack of rapid visual recovery, and recurrence years after complete resolution of initial manifestations. CONCLUSIONS: Acute exudative polymorphous vitelliform maculopathy can present with a more variable natural course than previously described. Paraneoplastic retinopathy and autosomal recessive bestrophinopathy closely resemble AEPVM, necessitating medical and hereditary evaluation to exclude these clinical possibilities. This series of patients with AEPVM expands the clinical spectrum of the disorder, including demographics, clinical manifestations, imaging features, natural course, and visual prognosis.

Accuracy of Self-reported Weight in Hispanic/Latino Adults of the Hispanic Community Health Study/Study of Latinos.

BACKGROUND: Previous US population-based studies have found that body weight may be underestimated when self-reported. However, this research may not apply to all US Hispanics/Latinos, many of whom are immigrants with distinct cultural orientations to ideal body size. We assessed the data quality and accuracy of self-reported weight in a diverse, community-based, US sample of primarily foreign-born Hispanic/Latino adults. METHODS: Using baseline data (2008-2011) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we described the difference between contemporaneous self-reported and measured current body weight (n = 16,119) and used multivariate adjusted models to establish whether the observed trends in misreporting in potential predictors of inaccuracy persisted after adjustment for other predictors. Last, we described the weighted percentage agreement in body mass classification using either self-reported or measured weight (n = 16,110). RESULTS: Self-reported weight was well correlated with (r = 0.95) and on average 0.23 kg greater than measured weight. The range of this misreporting was large and several factors were associated with misreporting: age group, gender, body mass categories, nativity, study site by background, unit of self-report (kg or lb), and end-digit preference. The percentage agreement of body mass classification using self-reported versus measured weight was 86% and varied across prevalent health conditions. CONCLUSIONS: The direction of misreporting in self-reported weight, and thus the anticipated bias in obesity prevalence estimates based on self-reported weights, may differ in US Hispanic/Latinos from that found in prior studies. Future investigations using self-reported body weight in US Hispanic/Latinos should consider this information for bias analyses.See video abstract at, http://links.lww.com/EDE/B276.

Whole exome sequencing of extreme age-related macular degeneration phenotypes.

PURPOSE: Demographic, environmental, and genetic risk factors for age-related macular degeneration (AMD) have been identified; however, a substantial portion of the variance in AMD disease risk and heritability remains unexplained. To identify AMD risk variants and generate hypotheses for future studies, we performed whole exome sequencing for 75 individuals whose phenotype was not well predicted by their genotype at known risk loci. We hypothesized that these phenotypically extreme individuals were more likely to carry rare risk or protective variants with large effect sizes. METHODS: A genetic risk score was calculated in a case-control set of 864 individuals (467 AMD cases, 397 controls) based on 19 common (≥1% minor allele frequency, MAF) single nucleotide variants previously associated with the risk of advanced AMD in a large meta-analysis of advanced cases and controls. We then selected for sequencing 39 cases with bilateral choroidal neovascularization with the lowest genetic risk scores to detect risk variants and 36 unaffected controls with the highest genetic risk score to detect protective variants. After minimizing the influence of 19 common genetic risk loci on case-control status, we targeted single variants of large effect and the aggregate effect of weaker variants within genes and pathways. Single variant tests were conducted on all variants, while gene-based and pathway analyses were conducted on three subsets of data: 1) rare (≤1% MAF in the European population) stop, splice, or damaging missense variants, 2) all rare variants, and 3) all variants. All analyses controlled for the effects of age and sex. RESULTS: No variant, gene, or pathway outside regions known to be associated with risk for advanced AMD reached genome-wide significance. However, we identified several variants with substantial differences in allele frequency between cases and controls with strong additive effects on affection status after controlling for age and sex. Protective effects trending toward significance were detected at two loci identified in single-variant analyses: an intronic variant in FBLN7 (the gene encoding fibulin 7) and at three variants near pyridoxal (pyridoxine, vitamin B6) kinase (PDXK). Aggregate rare-variant analyses suggested evidence for association at ASRGL1, a gene previously linked to photoreceptor cell death, and at BSDC1. In known AMD loci we also identified 29 novel or rare damaging missense or stop/splice variants in our sample of cases and controls. CONCLUSIONS: Identified variants and genes may highlight regions important in the pathogenesis of AMD and are key targets for replication.

DIDANOSINE RETINAL TOXICITY.

PURPOSE: To report nine new cases of retinal degeneration secondary to didanosine toxicity and to summarize the previously reported cases in the literature. METHODS: This was a multicenter, retrospective, observational case study from seven institutions. Medical records of patients who demonstrated well-demarcated severe midperipheral chorioretinal degeneration and who were previously treated with didanosine therapy were collected and the following information was reviewed: age, gender, medical history, detailed medication history including current and previous antiretroviral use, ocular and retinal examination findings, and multimodal imaging findings with optical coherence tomography, fundus photography, wide-field fundus autofluorescence, and wide-field fluorescein angiography. When available, findings with electrophysiology testing and automated perimetry were also collected and reviewed. A literature review was also performed to collect all reported cases of chorioretinal degeneration secondary to didanosine toxicity. RESULTS: Nine patients were identified who had findings consistent with peripheral retinal toxicity secondary to didanosine use. Eight of the 9 patients were men, and the median age was 54 years at the time of presentation (mean: 55 years, range, 42-71 years). Snellen distance acuity ranged from 20/20 to 20/32. At least three of the cases in the series demonstrated progression of the peripheral retinal pigment epithelium and photoreceptor atrophy despite didanosine cessation. A review of the literature revealed 10 additional cases of didanosine toxicity. Seven of the 10 cases were in men (70%), and the average age was 26 years with a wide range (2-54 years). Chorioretinal findings were very similar to this cohort. CONCLUSION: Herein, we report the largest series of nine cases of peripheral chorioretinal degeneration secondary to didanosine toxicity in adults. When combined with the cases in the literature, 19 cases of didanosine toxicity, 4 of which occurred in children, were collected and analyzed. Three of the new cases presented showed clear progression of degeneration despite didanosine cessation. Newer nucleoside reverse transcriptase inhibitors may potentiate mitochondrial DNA damage and lead to continued chorioretinal degeneration.

Estimating cumulative pathway effects on risk for age-related macular degeneration using mixed linear models.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the elderly in developed countries and typically affects more than 10% of individuals over age 80. AMD has a large genetic component, with heritability estimated to be between 45% and 70%. Numerous variants have been identified and implicate various molecular mechanisms and pathways for AMD pathogenesis but those variants only explain a portion of AMD's heritability. The goal of our study was to estimate the cumulative genetic contribution of common variants on AMD risk for multiple pathways related to the etiology of AMD, including angiogenesis, antioxidant activity, apoptotic signaling, complement activation, inflammatory response, response to nicotine, oxidative phosphorylation, and the tricarboxylic acid cycle. While these mechanisms have been associated with AMD in literature, the overall extent of the contribution to AMD risk for each is unknown. METHODS: In a case-control dataset with 1,813 individuals genotyped for over 600,000 SNPs we used Genome-wide Complex Trait Analysis (GCTA) to estimate the proportion of AMD risk explained by SNPs in genes associated with each pathway. SNPs within a 50 kb region flanking each gene were also assessed, as well as more distant, putatively regulatory SNPs, based on DNaseI hypersensitivity data from ocular tissue in the ENCODE project. RESULTS: We found that 19 previously associated AMD risk SNPs contributed to 13.3% of the risk for AMD in our dataset, while the remaining genotyped SNPs contributed to 36.7% of AMD risk. Adjusting for the 19 risk SNPs, the complement activation and inflammatory response pathways still explained a statistically significant proportion of additional risk for AMD (9.8% and 17.9%, respectively), with other pathways showing no significant effects (0.3% - 4.4%). DISCUSSION: Our results show that SNPs associated with complement activation and inflammation significantly contribute to AMD risk, separately from the risk explained by the 19 known risk SNPs. We found that SNPs within 50 kb regions flanking genes explained additional risk beyond genic SNPs, suggesting a potential regulatory role, but that more distant SNPs explained less than 0.5% additional risk for each pathway. CONCLUSIONS: From these analyses we find that the impact of complement SNPs on risk for AMD extends beyond the established genome-wide significant SNPs.

Hemorrhagic Ligamentum Flavum Cyst in the Adjacent Level of Lytic Spondylolisthesis - A Case of Diagnostic and Therapeutic Dilemma.

Introduction: Occurrence of hemorrhagic cyst inside ligamentum flavum is a very rare phenomenon and presents with back pain, radiculopathy, or neurogenic claudication. Various causes reported in the literature are trauma, anticoagulant therapy, and increased micromotion in the setting of unstable and degenerated motion segment. Case Report: We report a case of 41-year-old male patient who presented with claudication pain in both lower limbs for the past 6 months associated with bilateral calf atrophy. Plain radiograph with dynamic films showed lytic spondylolisthesis at L4-L5 level. Magnetic resonance imaging revealed a hemorrhagic cyst inside ligamentum flavum at the L3-L4 level occupying the posterior epidural space severely compressing the thecal sac. After a thorough diagnostic and therapeutic work up, we did a midline sparing decompression of L3-L4 level under microscope without fixing the listhetic segment. The patient had significant pain relief after surgery and doing well till now. Conclusion: In general, hemorrhagic cyst of ligamentum flavum is seen in a degenerated lumbar spine at the areas of increased micromotion and instability. Our case has shown that it can also occur in an adjacent segment of spondylolisthesis or instability. The obvious finding like listhesis in the adjacent segment may hinder a spine surgeon from diagnosing the cyst component and may guide to a erroneous treatment outline. Hence, it should not be missed in the imaging.

Genetic factors in nonsmokers with age-related macular degeneration revealed through genome-wide gene-environment interaction analysis.

Relatively little is known about the interaction between genes and environment in the complex etiology of age-related macular degeneration (AMD). This study aimed to identify novel factors associated with AMD by analyzing gene-smoking interactions in a genome-wide association study of 1207 AMD cases and 686 controls of Caucasian background with genotype data on 668,238 single nucleotide polymorphisms (SNPs) after quality control. Participants' history of smoking at least 100 cigarettes lifetime was determined by a self-administered questionnaire. SNP associations modeled the effect of the minor allele additively on AMD using logistic regression, with adjustment for age, sex, and ever/never smoking. Joint effects of SNPs and smoking were examined comparing a null model containing only age, sex, and smoking against an extended model including genotypic and interaction terms. Genome-wide significant main effects were detected at three known AMD loci: CFH (P = 7.51×10(-30) ), ARMS2 (P = 1.94×10(-23) ), and RDBP/CFB/C2 (P = 4.37×10(-10) ), while joint effects analysis revealed three genomic regions with P < 10(-5) . Analyses stratified by smoking found genetic associations largely restricted to nonsmokers, with one notable exception: the chromosome 18q22.1 intergenic SNP rs17073641 (between SERPINB8 and CDH7), more strongly associated in nonsmokers (OR = 0.57, P = 2.73 × 10(-5) ), with an inverse association among smokers (OR = 1.42, P = 0.00228), suggesting that smoking modifies the effect of some genetic polymorphisms on AMD risk.

Variants at chromosome 10q26 locus and the expression of HTRA1 in the retina.

Variations in a locus at chromosome 10q26 are strongly associated with the risk of age-related macular degeneration (AMD). The most significantly associated haplotype includes a nonsynonymous SNP rs10490924 in the exon 1 of ARMS2 and rs11200638 in the promoter region of HTRA1. It is under debate which gene(s), ARMS2, HTRA1 or some other genes are functionally responsible for the genetic association. To verify whether the associated variants correlate with a higher HTRA1 expression level as previously reported, HTRA1 mRNA and protein were measured in a larger human retina-RPE-choroid samples (n = 82). Results show there is no significant change of HTRA1 mRNA level among genotypes at rs11200638, rs10490924 or an indel variant of ARMS2. Furthermore, two AMD-associated synonymous SNPs rs1049331 and rs2293870 in HTRA1 exon 1 do not change its protein level either. These results suggest that the AMD-associated variants in the chromosome 10q26 locus do not significantly affect the expression of HTRA1.

A novel mutation at the N-terminal domain of the TIMP3 gene in Sorsby fundus dystrophy.

PURPOSE: To report a novel mutation occurring in the N-terminal domain of the tissue inhibitor of metalloproteinase 3 (TIMP3) gene in Sorsby fundus dystrophy. METHODS: Retrospective review of medical records of two patients who had clinical features consistent with Sorsby fundus dystrophy. Genetic testing confirmed a mutation in the TIMP3 gene in both patients. RESULTS: Both patients had findings of drusenlike deposits, retinal pigment epithelial and photoreceptor atrophy, and bilateral, recurrent choroidal neovascularization. A strong family history of early onset macular degeneration was present in both. The patients developed choroidal neovascularization at the age of 45 and 48 years, and both had multiple recurrences in both eyes. Genetic testing in both patients confirmed a heterozygous nucleotide change of C113G, causing a Ser38Cys change in Exon 1 of the N-terminal domain of the TIMP3 gene. CONCLUSION: All previously reported mutations in Sorsby fundus dystrophy occur at Exon 5 in the C-terminal domain. We report 2 patients with novel mutations in Exon 1 of the N-terminal domain. Although the mutation occurs at a different location on the TIMP3 gene, the clinical features are similar to other reported patients with Sorsby fundus dystrophy. This finding assists in understanding the pathogenesis of this disorder.

Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration.

We executed a genome-wide association scan for age-related macular degeneration (AMD) in 2,157 cases and 1,150 controls. Our results validate AMD susceptibility loci near CFH (P < 10(-75)), ARMS2 (P < 10(-59)), C2/CFB (P < 10(-20)), C3 (P < 10(-9)), and CFI (P < 10(-6)). We compared our top findings with the Tufts/Massachusetts General Hospital genome-wide association study of advanced AMD (821 cases, 1,709 controls) and genotyped 30 promising markers in additional individuals (up to 7,749 cases and 4,625 controls). With these data, we identified a susceptibility locus near TIMP3 (overall P = 1.1 x 10(-11)), a metalloproteinase involved in degradation of the extracellular matrix and previously implicated in early-onset maculopathy. In addition, our data revealed strong association signals with alleles at two loci (LIPC, P = 1.3 x 10(-7); CETP, P = 7.4 x 10(-7)) that were previously associated with high-density lipoprotein cholesterol (HDL-c) levels in blood. Consistent with the hypothesis that HDL metabolism is associated with AMD pathogenesis, we also observed association with AMD of HDL-c-associated alleles near LPL (P = 3.0 x 10(-3)) and ABCA1 (P = 5.6 x 10(-4)). Multilocus analysis including all susceptibility loci showed that 329 of 331 individuals (99%) with the highest-risk genotypes were cases, and 85% of these had advanced AMD. Our studies extend the catalog of AMD associated loci, help identify individuals at high risk of disease, and provide clues about underlying cellular pathways that should eventually lead to new therapies.

A 66-year-old woman with two weeks of distorted vision in the left eye.

PURPOSE: To report a case of concurrent melanoma metastasis to the orbit and MEK inhibitor-associated retinopathy. METHODS: Case report of a 66-year-old female patient undergoing mutation targeted MEK-inhibitor treatment for metastatic melanoma with retinal manifestations. RESULTS: After initiating MEK-inhibitor therapy our patient presented with bilateral blurred vision. Clinical examination and OCT imaging revealed multifocal bilateral serous retinal detachments consistent with MEKAR. Extrafoveal subretinal fluid foci resolved after discontinuation of MEK-inhibitor therapy, but her foveal lesions persisted for over 18 months. Years after her initial evaluation for MEKAR, our patient developed metamorphopsia in the left eye resulting from chorioretinal folds secondary to intraconal orbital metastasis. MRI revealed additional intracerebral and lung metastases, and the patient expired in 2 months. CONCLUSION: We report a case of prolonged MEKAR with concomitant orbital metastasis from melanoma. Multimodal imaging in conjunction with history and clinical features allows for disease identification and monitoring.

NIVOLUMAB-INDUCED HARADA-LIKE UVEITIS WITH BACILLARY DETACHMENT MIMICKING CHOROIDAL METASTASIS.

PURPOSE: To describe a patient with metastatic clear cell renal cell carcinoma in remission on maintenance nivolumab therapy who developed late-onset ocular toxicity manifesting as creamy chorioretinal lesions with exudative retinal detachment concerning for choroidal metastasis. METHOD: Case report. Main outcome measures include ophthalmoscopic examination, fundus photography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, spectral domain optical coherence tomography, and B-scan ultrasonography. RESULTS: A 49-year-old woman with a medical history of metastatic clear cell renal cell carcinoma in remission for two years after immunotherapy with four cycles of ipilimumab and nivolumab followed by maintenance nivolumab infusions developed lesions concerning for choroidal metastases in her right eye. Optical coherence tomography of the lesions revealed a bacillary layer detachment containing possible fibrinous exudate organized into layers and underlying choroidal thickening with chorioretinal folds. Later, choroidal thickening and chorioretinal folds also occurred in the left eye. Given that pan imaging detected no metastasis and the posterior segment abnormalities resolved after cessation of nivolumab and treatment with systemic corticosteroids, the patient was diagnosed with nivolumab-induced Vogt-Koyanagi-Harada-like uveitis. CONCLUSION: This case expands on the clinical spectrum of nivolumab-induced Vogt-Koyanagi-Harada-like uveitis, a condition that can also present with bacillary layer detachment mimicking an early choroidal metastasis, manifest asymmetrically in each eye, and develop after long-standing treatment.

NONSYNDROMIC RETINITIS PIGMENTOSA WITH BILATERAL RETINAL NEOVASCULARIZATION DUE TO HGSNAT MUTATION.

PURPOSE: To describe a case of nonsyndromic retinitis pigmentosa caused by presumed compound heterozygous A615T and T522M mutations in HGSNAT, characterized by bilateral cystoid macular edema and retinal neovascularization. METHODS: Case report. The patient underwent clinical evaluation, multimodal imaging, and next-generation panel sequencing. In silico analysis was performed with PolyPhen-2, SIFT, and MutationTaster. Segregation analysis was not available. RESULTS: A 35-year-old hypertensive man presented with nyctalopia, photopsia, and difficulty reading for six months. He had no family history of visual deficits. The best-corrected visual acuity was 20/25 in the right eye and 20/20 in the left eye. Examination revealed midperipheral bone spicules and macular neovascularization in both eyes. Multimodal imaging demonstrated cystoid macular edema, ellipsoid band loss outside the central macula, and leakage from the neovascularization in both eyes. Sequencing detected four mutations in three genes, including two heterozygous mutations in HGSNAT (c.1843G>A, p.A615T and c.1565C>T, p.T522M). A615T is a pathogenic, hypomorphic mutation. T522M has not been previously phenotypically described. It is predicted damaging by in silico analysis and occurs at a conserved position near the eighth transmembrane domain, adjacent to residues in which missense mutations result in protein misfolding. CONCLUSION: This is, to the best of our knowledge, the first reported case of retinal neovascularization in a case of nonsyndromic retinitis pigmentosa due to HGSNAT mutation. The T522M variant likely functions as a severe mutation alongside the hypomorphic A615T mutation. These findings expand the genotypic and phenotypic spectrum of nonsyndromic retinitis pigmentosa.

A 48-YEAR-OLD CAUCASIAN MAN WITH UNILATERAL "SMUDGE" IN INFERIOR VISUAL FIELD.

PURPOSE: To report an increasingly prevalent fundoscopic manifestation of syphilitic uveitis. METHODS: Case report of a patient with acute retinal necrosis secondary to syphilis. RESULTS: A 48-year-old man presented with decreased vision, anterior segment inflammation, and a wedge-shaped retinal lesion in the superior periphery, with a diaphanous leading edge extending down toward the superior arcade. The patient was HIV+ and poorly compliant with therapy. The top three differential diagnoses were herpetic necrotizing retinitis, syphilis, and lymphoma. An extensive lab workup was positive for syphilis. The patient was treated with IV penicillin G and demonstrated improvement in visual acuity and examination. CONCLUSION: There have been an increasing number of reports of syphilis patients, especially in the population of men who have sex with men, who present with fundus findings similar to acute retinal necrosis. These findings include a characteristic ground glass, translucent appearance of unifocal or multifocal lesions, primarily affecting the inner retina and sometimes associated with co-localizing occlusive vasculitis. Treatment with IV penicillin G is warranted and has demonstrated good visual recovery.

The ARMS2 A69S variant and bilateral advanced age-related macular degeneration.

PURPOSE: To identify genetic associations between specific risk genes and bilateral advanced age-related macular degeneration (AMD) in a retrospective, observational case series of 1,003 patients: 173 patients with geographic atrophy in at least 1 eye and 830 patients with choroidal neovascularization in at least 1 eye. METHODS: Patients underwent clinical examination and fundus photography. The images were subsequently graded using a modified grading system adapted from the Age-Related Eye Disease Study. Genetic analysis was performed to identify genotypes at 4 AMD-associated variants (ARMS2 A69S, CFH Y402H, C3 R102G, and CFB R32Q) in these patients. RESULTS: There were no statistically significant relationships between clinical findings and genotypes at CFH, C3, and CFB. The genotype at ARMS2 correlated with bilateral advanced AMD using a variety of comparisons: unilateral geographic atrophy versus bilateral geographic atrophy (P = 0.08), unilateral choroidal neovascularization versus bilateral choroidal neovascularization (P = 9.0 × 10(-8)), and unilateral late AMD versus bilateral late AMD (P = 5.9 × 10(-8)). CONCLUSION: In this series, in patients with geographic atrophy or choroidal neovascularization in at least 1 eye, the ARMS2 A69S substitution strongly associated with geographic atrophy or choroidal neovascularization in the fellow eye. The ARMS2 A69S substitution may serve as a marker for bilateral advanced AMD.