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Purpose: To describe eight patients with toxoplasma retinochoroiditis following exposure to wild game. Methods: Retrospective, multicenter case series Results: Eight men, aged 29 to 71 (mean, 56 ye...

Importance Advanced age-related macular degeneration (AMD) is a leading cause of blindness in Western countries. Causal, modifiable risk factors need to be identified to develop preventive measures for advanced AMD. Objective To assess whether smoking, alcohol consumption, blood pressure, body mass index, and glycemic traits are associated with increased risk of advanced AMD. Design, Setting, Participants This study used 2-sample mendelian randomization. Genetic instruments composed of variants associated with risk factors at genome-wide significance (P

Age-related macular degeneration (AMD) is a leading cause of irreversible visual loss and is primarily treated with nutritional supplementation as well as with anti-vascular endothelial growth factor (VEGF) agents for certain patients with neovascular disease. AMD is a complex disease with both genetic and environmental risk factors. In addition, treatment outcomes from nutritional supplementation and anti-VEGF agents vary considerably. Therefore, it is reasonable to suspect that there may be pharmacogenetic influences on these treatments. Many series have reported individual associations with variants in complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2), and other loci. However, at this time there are no validated associations. With respect to AMD, pharmacogenetics remains an intriguing area of research but is not helpful for routine clinical management.

Age-related macular degeneration (AMD) is the most common cause of permanent central visual acuity loss in persons over 65 years of age in industrialized nations. Today, intravitreal vascular endothelial growth factor (VEGF) inhibitors are the mainstay of treatment worldwide. Areas covered: The following review covers the current treatments and challenges of wet AMD management. It also covers emerging therapies including radiation, latest generation anti-VEGF agents, and combination therapies. Expert opinion: Current neovascular AMD therapy is aimed at decreasing the VEGF effect at the choroidal neovascularization (CNV) complex. The most important existing challenges in the treatment of neovascular AMD are improving visual outcomes, decreasing the treatment burden, and minimizing geographic atrophy. Clinicians are using many treatment strategies to minimize intravitreal injections without sacrificing visual outcomes. Combination of anti-VEGF therapy with other previously available treatments that target a different pathophysiological mechanism may be a reasonable clinical strategy to minimize intravitreal injections. Many exciting novel drugs that target newly discovered pathways associated with CNV development and progression hold clinical promise. The results of ongoing randomized clinical trials will answer the important concerns surrounding new drugs and delivery devices: safety and visual outcomes.

A 70-year-old Caucasian gentleman presented with decreased vision in the left eye and a subtle whitish macular plaque in the left eye and pigment mottling bilaterally. Indocyanine green angiography...

PURPOSE: To report spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) documentation of late stage macular findings associated with Sjogren-Larsson Syndrome in three adult siblings. METHODS: Three adult siblings with Sjogren-Larrson Syndrome underwent ophthalmic examination and imaging. RESULTS: Crystalline maculopathy and subretinal deposits, presumably lipofuscin accumulation, with macular atrophy were present in varying degrees in all three adult siblings. DISCUSSION: In adults with Sjogren-Larsson Syndrome, crystalline retinopathy can progress to macular atrophy and the appearance of lipofuscin accumulation.

Three adult siblings with Sjögren-Larsson syndrome (SLS) demonstrated signs of late-stage SLS maculopathy, including intraretinal crystals, atrophic changes, and lipofuscin deposition. This first report of SLS maculopathy imaged with optical coherence tomography angiography revealed decreased retinal capillary density, vessel dilation, and increased flow voids in the superficial and deep capillary plexuses. [ Ophthalmic Surg Lasers Imaging Retina . 2018;49:e78–e82.]

Crystalline retinopathies may be associated with different etiologies including genetic, toxic, degenerative, idiopathic, and iatrogenic causes. We outline the various types of crystalline retinopathies and summarize their associated etiologies, pathogenesis, clinical presentations, multimodal imaging findings, and management strategies.

Optical coherence tomography angiography (OCTA) is a recently established noninvasive technology for evaluation of the retinal and choroidal vasculature. The literature regarding the findings in macular telangiectasia type 2 (MacTel2) is scarce. We report the OCTA findings associated with a subject with MacTel2 and secondary subretinal neovascularization (SNV). The commercially available Cirrus 5000 with AngioPlex (Zeiss, Jena, Germany) was used, without any subsequent image modification or processing. Subretinal neovascularization was detectable with OCTA at the level of the outer retina and choriocapillaris. Microvascular abnormalities associated with MacTel2 were present mostly in the deep capillary plexus of the retina temporally.

BACKGROUND AND OBJECTIVE: When delivered via a single intravitreal injection, ocriplasmin can effect proteolytic resolution of symptomatic vitreomacular adhesion (VMA). The authors describe their initial clinical experience with ocriplasmin at a large academic center. PATIENTS AND METHODS: Retrospective review of all patients with symptomatic VMA treated with ocriplasmin from January 2013 through May 2013 at a single center. RESULTS: Nineteen patients with symptomatic VMA received intravitreal ocriplasmin. Eight patients (42%) exhibited resolution of VMA. Macular holes in three of six patients (50%) closed after injection. A higher proportion of VMA resolution was observed in patients with the following baseline characteristics: age less than 65 years, focal adhesions less than or equal to 1,500 μm, presence of macular hole, phakic status, and absence of epiretinal membrane. CONCLUSION: Initial clinical outcomes using ocriplasmin in this study are consistent with those reported in the phase 3 clinical trials. Improved clinical results can be achieved with careful case selection based on specific baseline characteristics. [ Ophthalmic Surg Lasers Imaging Retina. 2013;44:334–343.]

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

Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate the understanding of AMD biology and help design new therapies, we executed a collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 loci associated at P

Purpose Progression rate of age-related macular degeneration (AMD) varies substantially, yet its association with genetic variation has not been widely examined. Methods We tested whether progression rate from intermediate AMD to geographic atrophy (GA) or choroidal neovascularization (CNV) was correlated with genotype at seven single nucleotide polymorphisms (SNPs) in the four genes most strongly associated with risk of advanced AMD. Cox proportional hazards survival models examined the association between progression time and SNP genotype while adjusting for age and sex and accounting for variable follow-up time, right censored data, and repeated measures (left and right eyes). Results Progression rate varied with the number of risk alleles at the CFH:rs10737680 but not the CFH:rs1061170 (Y402H) SNP; individuals with two risk alleles progressed faster than those with one allele (hazard ratio [HR] = 1.61, 95% confidence interval [CI] = 1.08-2.40, P < 0.02, n = 547 eyes), although this was not significant after Bonferroni correction. This signal was likely driven by an association at the correlated protective variant, CFH:rs6677604, which tags the CFHR1-3 deletion; individuals with at least one protective allele progressed more slowly. Considering GA and CNV separately showed that the effect of CFH:rs10737680 was stronger for progression to CNV. Conclusions Results support previous findings that AMD progression rate is influenced by CFH, and suggest that variants within CFH may have different effects on risk versus progression. However, since CFH:rs10737680 was not significant after Bonferroni correction and explained only a relatively small portion of variation in progression rate beyond that explained by age, we suggest that additional factors contribute to progression.

Age-related macular degeneration is a complex disease, with both genetic and environmental risk factors interacting in unknown ways. Currently, 52 gene variants within 34 loci have been significantly associated with age-related macular degeneration. Two well-studied major genes are complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2). There exist several commercially available tests that are proposed to stratify patients into high-risk and low-risk groups, as well as predict response to nutritional supplementation. However, at present, the bulk of the available peer-reviewed evidence suggests that genetic testing is more useful as a research tool than for clinical management of patients.

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.

A 69-year-old woman presented with a “veil” over the left eye. Clinical examination demonstrated signs of central retinal artery occlusion. Visual acuity was compromised to 1/200E in the left eye. Ocular massage and anterior chamber paracentesis failed to improve vision. An emergent intra-arterial catheterization with verapamil and alteplase infusion was performed less than 12 hours following symptom onset. Initial optical coherence tomography (OCT) showed inner retinal edema. One year later, OCT revealed relatively minor thinning, which could explain the patient’s visual recovery to 20/40. This may be the first article to report OCT changes following this treatment for central retinal artery occlusion. [ Ophthalmic Surg Lasers Imaging Retina. 2015;46:77–79.]

Summary Age-related macular degeneration (AMD) is a complex degenerative retinal disease influenced by both genetic and environmental risk factors. We assessed whether single nucleotide polymorphisms (SNPs) in the NOS2A gene increase risk and modulate the effect of smoking in AMD. 998 Caucasian subjects (712 AMD cases and 286 controls) were genotyped for 17 SNPs in NOS2A. Multivariable logistic regression models containing SNP genotypes, age, sex, smoking status and genotype/smoking interaction were constructed. SNP rs8072199 was significantly associated with AMD (OR = 1.3; 95% CI : 1.02, 1.65; P= 0.035). A significant interaction with smoking was detected at rs2248814 (P= 0.037). Stratified data by genotypes demonstrated that the association between AMD and smoking was stronger in carriers of AA genotypes (OR = 35.98; 95% CI: 3.19, 405.98) than in carriers of the AG genotype (OR = 3.05; 95% CI: 1.36, 6.74) or GG genotype (OR = 2.1; 95% CI: 0.91, 4.84). The results suggest a possible synergistic interaction of AA genotype with smoking, although the result bears replication in larger samples. Our data suggests that SNPs in the NOS2A gene are associated with increased risk for AMD and might modulate the effect of smoking on AMD.

Contains fulltext : 167823.pdf (Publisher’s version ) (Open Access) PURPOSE: Age-related macular degeneration is a common form of vision loss affecting older adults. The etiology of AMD is multifactorial and is influenced by environmental and genetic risk factors. In this study, we examine how 19 common risk variants contribute to drusen progression, a hallmark of AMD pathogenesis. METHODS: Exome chip data was made available through the International AMD Genomics Consortium (IAMDGC). Drusen quantification was carried out with color fundus photographs using an automated drusen detection and quantification algorithm. A genetic risk score (GRS) was calculated per subject by summing risk allele counts at 19 common genetic risk variants weighted by their respective effect sizes. Pathway analysis of drusen progression was carried out with the software package Pathway Analysis by Randomization Incorporating Structure. RESULTS: We observed significant correlation with drusen baseline area and the GRS in the age-related eye disease study (AREDS) dataset (rho = 0.175, P = 0.006). Measures of association were not statistically significant between drusen progression and the GRS (P = 0.54). Pathway analysis revealed the cell adhesion molecules pathway as the most highly significant pathway associated with drusen progression (corrected P = 0.02). CONCLUSIONS: In this study, we explored the potential influence of known common AMD genetic risk factors on drusen progression. Our results from the GRS analysis showed association of increasing genetic burden (from 19 AMD associated loci) to baseline drusen load but not drusen progression in the AREDS dataset while pathway analysis suggests additional genetic contributors to AMD risk.

A 60-year-old man diagnosed with macular telangiectasia type 1 (MacTel 1) was treated for 3 years with monthly aflibercept (Eylea; Regeneron, Tarrytown, NY) and serially imaged with spectral-domain optical coherence tomography. When administered monthly, aflibercept appeared to have a beneficial effect on macular edema secondary to MacTel 1. Visual acuity preservation despite minimal chronic macular edema could be attributed to the lack of significant photoreceptor disruption. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:593–595.]

The Age-Related Eye Disease Study (AREDS) recommended treatment with antioxidants plus zinc in patients with intermediate or advanced age-related macular degeneration in order to reduce progression risks. Recent pharmacogenetic studies have reported differences in treatment outcomes with respect to variants in genes for CFH and ARMS2, although the treatment recommendations based on these differences are controversial. Different retrospective analyses of subsets of patients from the same AREDS trial have drawn different conclusions. The practicing clinician, who is not an expert on genetics, clinical trial design, or statistical analysis, may be uncertain how to interpret these results. Based on the balance of the available literature, we suggest not changing established practice recommendations until additional evidence from clinical trials becomes available.

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. Electronic supplementary material The online version of this article (doi:10.1186/s12859-015-0760-4) contains supplementary material, which is available to authorized users.

Evaluation of: Sallo FB, Leung BA, Chung M et al. MacTel Study Group. Retinal crystals in type 2 idiopathic macular telangiectasia. Ophthalmology 118, 2461–2467 (2011).Idiopathic macular telangiectasia (MacTel) is a bilateral anomaly of retinal capillaries that involves the juxtafoveal region around the horizontal raphe. Clinical features include intraretinal crystalline deposits, subretinal pigment plaques, right-angle vessels, inner lamellar cysts and, in some cases, subretinal neovascularization. Currently, there is no effective treatment for this condition and the etiology is unknown. Funded by the Lowy Medical Research Institute Ltd., the MacTel Study Project is a worldwide multicenter endeavor dedicated to exploring the causes of MacTel and investigating possible treatments. In the featured article, the study group characterizes the intraretinal crystalline deposits associated with MacTel.

PURPOSE To describe hypertensive optic neuropathy and choroidopathy caused by renal failure in an 18-year-old woman. METHODS The clinical and angiographic findings of a young patient with hypertensive optic neuropathy and choroidopathy caused by hypertensive emergency secondary to renal failure are described. RESULTS The patient's visual acuity, bilateral optic nerve swelling, and macular edema improved with blood pressure control. Several small areas of exudative retinal detachment remain. CONCLUSION Accelerated or malignant hypertension is a common cause of bilateral optic nerve swelling and exudative retinal detachments. Treatment of systemic hypertension is essential in reversing the ocular manifestations of the condition.

BACKGROUND AND OBJECTIVE: To assess the incidence and outcomes of infectious endophthalmitis after intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents. PATIENTS AND METHODS: Patient records at the Bascom Palmer Eye Institute (BPEI) from January 1, 2005, through December 31, 2014, were reviewed. The largest commercial claims and encounters database in the U.S. (MarketScan) was utilized to calculate the population-based endophthalmitis rate for 2011 to 2013. RESULTS: The population-based rate of endophthalmitis after anti-VEGF injections for 2011 to 2013 was 391/740,757 (0.053%). BPEI’s rate was 20/121,285 (0.016%) during the study period: eight after bevacizumab (0.012%), six after ranibizumab (0.018%), and six after aflibercept (0.031%) injection. Nine BPEI cases (45%) were culture-positive: Streptococcus species (5), coagulase-negative Staphylococcus (3), and non-anthracis Bacillus (1). Final visual acuity varied from 20/25 to no light perception. CONCLUSION: Endophthalmitis after anti-VEGF injection was uncommon in our institution and in the population-based database. Treatment outcomes were variable but generally fared better in the culture-negative cases. [ Ophthalmic Surg Lasers Imaging Retina . 2015;46:643–648.]

Awhitewoman inher late70spresentedwithanasymptomaticchoroidal macrovessel in the right eye in the setting of non-neovascular age-relatedmaculardegeneration (AMD)(Figure).1,2Thepatienthad afamilyhistoryofAMDandhermedicalhistorywassignificantforcataract surgery in both eyes, hypothyroidism, migraine headaches, chronic pancreatitis, and urinary incontinence. Her medications included Age-Related Eye Disease Study 2 vitamin supplementation. Her best-corrected visual acuity was stable at 20/30 OU and intraocular pressure was normal at 15mmHgOD and 13mmHgOS. Non-neovascular AMDwas present in the left eye aswell.

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.

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.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.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)).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.

This chapter provides a review of the discovery of anti-vascular endothelial growth factor (VEGF) agents, the evolution of drug development, and the refinement of evidence-based treatment strategies for neovascular AMD.

To assess the rate of infectious endophthalmitis and to describe the clinical and microbiological features of eyes that develop clinically suspected endophthalmitis after an intravitreal injection of vascular endothelial growth factor antagonists.The medical records of patients undergoing intravitreal injections of anti-vascular endothelial growth factor agents from January 1, 2005, through December 31, 2010, at a single university referral center and associated satellite clinics were retrospectively analyzed to determine the rate of infectious endophthalmitis after intravitreal anti-vascular endothelial growth factor injections.Twelve cases (11 patients) of clinically suspected endophthalmitis were identified after a total of 60,322 injections (0.02%; 95% confidence interval, 0.0114%-0.0348%). Of the 12 cases, 11 presented within 3 days of the injection. Of the 7 culture-positive cases, 5 were because of Streptococcus species. In 4 of the 5 Streptococcus cases, final visual acuity was hand motions or worse. The rate of clinically suspected endophthalmitis was 0.018% after bevacizumab and 0.027% after ranibizumab injections.A very low rate of endophthalmitis after intravitreal injections of anti-vascular endothelial growth factor agents was observed. Patients typically presented within 3 days of injection. Streptococcus species was the most common bacteria isolated, and it was generally associated with poor visual outcomes.

Over the past few years, antivascular endothelial growth factor (VEGF) therapy has become a standard treatment for neovascular age-related macular degeneration (AMD). During this time, treatment strategies have evolved from a monthly dosing schedule to individualized regimens. This paper will review the currently available anti-VEGF agents and evidence-based treatment strategies.

Persistent placoid maculopathy is a rare entity characterized by bilateral well-delineated whitish plaque-like lesions in the macula. Secondary choroidal neovascularization and extensive retinal pigment epithelial damage, highlighted by spectral domain optical coherence tomography and autofluorescence imaging, can limit visual prognosis. Aggressive immunosuppression can preserve vision and perhaps delay the onset of choroidal neovascularization.

Purpose To report the first case of endophthalmitis after Descemet's stripping with automated endothelial keratoplasty caused by Mycobacterium abscessus. Methods Observational case report. Results An immunocompetent 88-year-old woman presented with endophthalmitis 2 months after a routine Descemet's stripping with automated endothelial keratoplasty resulting in decreased visual acuity and persistent vitreous opacities despite aggressive medical treatment. She underwent eventual pars plana vitrectomy with explantation of the posterior chamber intraocular lens and tube shunt. Operative cultures isolated Mycobacterium abscessus. With continued antibiotic therapy, the endophthalmitis eventually resolved with significant improvement of visual acuity. Conclusions We report a case of endophthalmitis as a complication of Descemet's stripping with automated endothelial keratoplasty. Although a rare pathogen in endophthalmitis, M. abscessus is difficult to culture and treat. Surgical hypotony combined with contamination of intraoperative materials and/or postsurgical drops are the likely mechanisms of infection.

A patient presented with subfoveal choroidal neovascularization associated with angioid streaks and was treated with three intravitreal injections of off-label bevacizumab (1.25 mg) in the right eye. Visual acuity improved from 20/70 to 20/20 and remained at this level for 32 months. In certain patients with choroidal neovascularization from angioid streaks, intravitreal bevacizumab may produce normalization of visual acuity and macular anatomy for an extended period of time. [Ophthalmic Surg Lasers Imaging 2009;40:77-79.]

Purpose: To determine if inhibition of vascular endothelial growth factor-A affects visual acuity, fluorescein angiographic, and optical coherence tomography outcomes in patients with perifoveal telangiectasia (PT), also referred to as macular telangiectasia, Type 2 and previously known as juxtafoveolar retinal telangiectasis group 2A. Methods: A retrospective review of patients with PT treated with intravitreal bevacizumab was performed at the Bascom Palmer Eye Institute. Best-corrected visual acuity, fluorescein angiography, and optical coherence tomography measurements were performed. Results: Nine eyes of eight patients were identified. Five of these eyes had proliferative PT characterized by subretinal neovascularization involving the macula. After treatment, follow-up ranged from 4 to 27 months. The mean best-corrected visual acuity remained stable for the four eyes with nonproliferative PT. In the five eyes with proliferative PT, best-corrected visual acuity was unchanged or improved after treatment. All eyes demonstrated decreased intraretinal leakage on fluorescein angiography after an injection of bevacizumab, and eyes with proliferative PT showed decreased growth and leakage of the subretinal neovascularization. The mean decrease in optical coherence tomography central retinal thickness was less than 30 μm. Conclusion: In nonproliferative PT, intravitreal bevacizumab decreases fluorescein angiographic leakage in PT but has no short-term effect on visual acuity or optical coherence tomography appearance. In proliferative PT, intravitreal bevacizumab arrests the leakage and growth of subretinal neovascularization with the possibility of visual acuity improvement.

Best's disease is an autosomal dominant disorder characterized by bilateral vitelliform macular lesions that progress through several stages throughout life. The authors describe a 20-month-old child with hereditary Best's disease inherited from his father. To their knowledge, this is the youngest child to be diagnosed as having Best's disease using photographic documentation.

To identify factors associated with best-corrected visual acuity (BCVA) presentation and 2-year outcome in 479 intermediate, posterior, and panuveitic eyes.Cohort study using randomized controlled trial data.Multicenter Uveitis Steroid Treatment (MUST) Trial masked BCVA measurements at baseline and at 2 years follow-up used gold-standard methods. Twenty-three clinical centers documented characteristics per protocol, which were evaluated as potential predictive factors for baseline BCVA and 2-year change in BCVA.Baseline factors significantly associated with reduced BCVA included age ≥50 vs50 years; posterior vs intermediate uveitis; uveitis duration10 vs6 years; anterior chamber (AC) flaregrade 0; cataract; macular thickening; and exudative retinal detachment. Over 2 years, eyes better than 20/50 and 20/50 or worse at baseline improved, on average, by 1 letter (P = .52) and 10 letters (P.001), respectively. Both treatment groups and all sites of uveitis improved similarly. Factors associated with improved BCVA included resolution of active AC cells, resolution of macular thickening, and cataract surgery in an initially cataractous eye. Factors associated with worsening BCVA included longer duration of uveitis (6-10 or10 vs6 years), incident AC flare, cataract at both baseline and follow-up, pseudophakia at baseline, persistence or incidence of vitreous haze, and incidence of macular thickening.Intermediate, posterior, and panuveitis have a similarly favorable prognosis with both systemic and fluocinolone acetonide implant treatment. Eyes with more prolonged/severe inflammatory damage and/or inflammatory findings initially or during follow-up have a worse visual acuity prognosis. The results indicate the value of implementing best practices in managing inflammation.

Purpose:Age-Related Macular Degeneration (AMD) is the leading cause of irreversible visual loss in developed countries. Its etiology includes genetic and environmental factors. Although VEGFA variants are associated with AMD, the joint action of variants within the VEGF pathway and their interaction with non-genetic factors has not been investigated. Methods:Affymetrix 6.0 chipsets were used to genotype 668,238 SNPs in 1,207 AMD cases and 686 controls. Environmental exposures were collected by questionnaire. A set-based test was conducted using the chi-square statistic at each SNP derived from Kraft's 2df joint test. Pathway and gene-based test statistics were calculated as the mean of all independent SNP statistics. Phenotype labels were permuted 10,000 times to generate an empirical p-value. Results: While a main effect of the VEGF pathway was not identified, the pathway was associated with neovascular AMD in women when accounting for birth control pill (BCP) use (P= 0.017). Analysis of VEGF's subpathways found that SNPs in the Proliferation subpathway were associated with neovascular AMD (P=0.029) when accounting for BCP use. Nominally significant genes within this subpathway were also observed. Stratification by BCP use revealed novel significant genetic effects in women who had taken BCPs. Conclusions: These results illustrate that some AMD genetic risk factors may only be revealed when considering complex relationships among risk factors. This shows the utility of exploring pathways of previously associated genes to find novel effects. It also demonstrates the importance of incorporating environmental exposures in tests of genetic association at the SNP, gene, or pathway level.

Purpose. To investigate whether female reproductive history and hormone replacement therapy (HRT) or birth control pills (BCPs) influence risk for age-related macular degeneration (AMD) and whether genetic factors interact with HRT to modulate AMD risk. Methods. Related and unrelated female participants (n = 799) were examined and data were analyzed with generalized estimating equations with adjustment for age and smoking. Individuals with AMD grades 1 to 2 were considered to be unaffected (n = 239) and those with grades 3 to 5 were considered affected (n = 560). Results. When comparing all cases with controls, significant inverse associations were observed for HRT (odds ratio [OR] = 0.65, 95% CI 0.48-0.90, P = 0.008) and BCPs (OR = 0.60, 95% CI 0.36-0.10, P = 0.048). When analyses were stratified by AMD severity (early versus geographic atrophy versus neovascular), the inverse association remained significant (HRT OR = 0.45, 95% CI 0.30-0.66, P < 0.0001; BCP OR = 0.55, 95% CI 0.32-0.96, P = 0.036) only when comparing neovascular AMD with the control. All pair-wise HRT-genotype and BCP-genotype interactions were examined, to determine whether HRT or BCP modifies the effect of established genetic risk factors. The strongest interactions were observed for HRT x ARMS2 coding SNP (R73H) rs10490923 (P = 0.007) and HRT x ARMS2 intronic SNP rs17623531 (P = 0.019). Conclusions. These findings provide the first evidence suggesting that ARMS2 interacts with HRT to modulate AMD risk and are consistent with previous reports demonstrating a protective relationship between exogenous estrogen use and neovascular AMD. These results highlight the genetic and environmental complexity of the etiologic architecture of AMD; however, further replication is necessary to validate them.