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Diabetic macular edema (DME) remains an important worldwide cause of visual loss. Corticosteroids have a role in the treatment of some patients with advanced or recurrent DME. The best studied steroids for this indication are triamcinolone acetonide, dexamethasone, and fluocinolone acetonide. All steroids are associated with risks of cataract and intraocular pressure elevation. In addition, intravitreal injection of any medication is associated with risks of infectious endophthalmitis, which has led to the investigation of various extended-release steroid implants. At this time, no steroid is approved by the United States Food and Drug Administration (FDA) for the treatment of DME.

Patients with prominent vitreous opacities may demonstrate a characteristic shadowing on the volume-scanning protocols using spectral-domain optical coherence tomography. The authors present five cases of this characteristic shadowing artifact. This finding may be useful in objectively documenting the status of vitreous opacification and verifying the patient’s complaint of symptomatic floaters, a so-called “floater scotoma.” [ Ophthalmic Surg Lasers Imaging Retina. 2013;44:415–418.]

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.]

Update on controversies in the surgical management of rhegmatogenous retinal detachment.There are multiple new reports regarding the development and management of retinal detachment. Current use of oral fluoroquinolones may be associated with onset of retinal detachment, although the clinical relevance of this correlation is uncertain at this time and the finding has not been replicated in subsequent studies. Pars plana vitrectomy (PPV) continues to demonstrate efficacy as a primary treatment for retinal detachment, especially in pseudophakic patients. In many patients with macula-on retinal detachment, scheduling surgery after a short time delay is not necessarily deleterious and may actually be beneficial. Novel surgical tools, including bioerodible scleral buckling materials and artificial vitreous substitutes, are being investigated.Retinal detachment remains an important cause of visual loss. Although current surgical techniques demonstrate high rates of anatomic and visual success, further advances will probably benefit patients with retinal detachment.

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

An 11-year-old patient was diagnosed with tuberous sclerosis complex based on retinal and cutaneous findings and confirmed by genetic testing. Spectral-domain optical coherence tomography (OCT) demonstrated subtle solid intraretinal tumors that focally replaced the inner retina and displaced the outer retinal layers. OCT angiography demonstrated prominent intrinsic vascularity but no feeder vessels. [ Ophthalmic Surg Lasers Imaging Retina . 2017;48:756–758.]

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.

Acute-onset postoperative endophthalmitis after cataract surgery remains a rare but important cause of visual loss. There is no global consensus regarding the optimal strategies for prophylaxis of endophthalmitis and practices vary substantially around the world, especially with respect to the use of intracameral antibiotics. The European Society of CataractRefractive Surgeons in a randomized clinical trial (2007) reported an approximately 5-fold reduction in endophthalmitis rates associated with the use of intracameral cefuroxime. Despite this report, the use of intracameral antibiotics has not been universally adopted.Various endophthalmitis prophylaxis patterns around the world (including the United States, Canada, Australia/New Zealand, Japan, China, India, Indonesia, South Africa, Argentina, Russia, Sweden and Mexico) are compared. Each contributing author was asked to provide similar information, including endophthalmitis rates based on published studies, current practice patterns, and in some cases original survey data. Various methods were used to obtain this information, including literature reviews, expert commentary, and some new survey data not previously published.Many different practice patterns were reported from around the world, specifically with respect to the use of intracameral antibiotics.There is no worldwide consensus regarding endophthalmitis prophylaxis with cataract surgery.

Elevation of intraocular pressure (IOP) due to therapeutic use of glucocorticoids is called steroid-induced ocular hypertension (SIOH); this can lead to steroid-induced glaucoma (SIG). Glucocorticoids initiate signaling cascades ultimately affecting expression of hundreds of genes; this provides the potential for a highly personalized pharmacological response. Studies attempting to define genetic risk factors were undertaken early in the history of glucocorticoid use, however scientific tools available at that time were limited and progress stalled. In contrast, significant advances were made over the ensuing years in defining disease pathophysiology. As the genomics age emerged, it appeared the time was right to renew investigation into genetics. Pharmacogenomics is an unbiased discovery approach, not requiring an underlying hypothesis, and provides a way to pinpoint clinically significant genes and pathways that could not have been discovered any other way. Results of the first genome-wide association study to identify polymorphisms associated with SIOH, and follow-up on two novel genes linked to the disorder, GPR158 and HCG22, is discussed in the second half of the article. However, knowledge of genetic variants determining response to steroids in the eye also has value in its own right as a predictive and diagnostic tool. This article concludes with a discussion of how the Precision Medicine Initiative®, announced by U.S. President Obama in his 2015 State of the Union address, is beginning to touch the practice of ophthalmology. It is argued that SIOH/SIG may provide one of the next opportunities for effective application of precision medicine.

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.

Intraocular pharmacotherapy (vascular endothelial growth factor [VEGF] inhibitors and corticosteroids) has become first-line therapy for diabetic retinopathy (DR). A series of intraocular injections is usually required before disease modulation decreases the treatment burden in some patients, but others with chronic diabetic macular edema may require intensive longer-term therapy.Recent studies showing successful pharmacologic treatment of proliferative DR will probably lead to increased use of pharmacotherapy, thereby further emphasizing the need for longer duration drugs. Recently approved anti-VEGF drugs (aflibercept) and corticosteroids (dexamethasone and fluocinolone inserts) provide extended durations of action. Longer action anti-VEGF molecules, sustained release devices and pumps, and encapsulated cell technology, may further decrease treatment burden, though regulatory approval may not occur for at least 5 years. Oral medications (danazol and minocycline) and modified topical drugs (loteprednol) will require daily administration but may decrease the frequency of visits to physicians' offices. Intravitreally administered drugs that target different biochemical pathways are being developed as monotherapy and combination therapy, and their effects on durability remains to be seen.The rich development pipeline promises to provide improved therapeutic options in addition to drugs and devices with longer duration of action.

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.

There are many reasons to suspect a genetic influence on the development and progression of diabetic retinopathy, including substantial variability in disease severity among patients with similar risk factors. Linkage studies have suggested associations with chromosomes 1, 3, 12 and others. The most studied individual genes are those encoding vascular endothelial growth factor, aldose reductase, and the receptor for advanced glycation end products, all of which have shown statistically significant associations in multiple series from various parts of the world. At this time, no definite genetic associations with diabetic retinopathy have been consistently reported. This may be due to small sample sizes, differences in study design, underlying genetic differences between study populations, or other factors. As we continue to collect data, these relationships may become more clear.

The role of intravitreal triamcinolone acetonide (IVTA) for patients with diabetic macular edema is controversial. Three diabetic macular edema case studies are presented to illustrate short-term outcomes. The main outcome measures included visual acuity (VA), optical coherence tomography (OCT), macular thickening (in microns), and improvement in visual acuity. IVTA appears to have short-term efficacy in selected patients with diabetic macular edema, and it is a reasonable treatment option for patients with very poor presenting VA. A controlled prospective study to evaluate the emerging role of IVTA in combination with other treatment options for diabetic macular edema, especially among patients with poor VA at presentation, is underway through the Diabetic Retinopathy Clinical Research network.

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.

A patient presented with acute-onset, postoperative endophthalmitis and visual acuity of light perception. Because of a time delay in arranging a pars plana vitrectomy (PPV), the patient was treated with a prompt vitreous tap for culture an injection of vancomycin and ceftazidime. Four hours later, the PPV was performed and additional antibiotics were injected. The cultures from both the initial needle tap and the subsequent PPV isolated methicillin-resistant Staphylococcus epidermidis sensitive to vancomycin, but resistant to fourth-generation fluoroquinolones. The patient eventually recovered a visual acuity of 20/80 before developing retinal detachment. This case illustrates the time lag necessary to sterilize the vitreous cavity, and suggests a possible two-step staged treatment strategy for situations in which access to PPV equipment and support staff may be limited.

Golnaz Javey1, Stephen G Schwartz2, Andrew A Moshfeghi2, Sanjay Asrani3, Harry W Flynn Jr21Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX, USA; 2Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA; 3Department of Ophthalmology, Duke University Medical Center, Durham, NC, USAAbstract: A patient presented with acute-onset, postoperative endophthalmitis and visual acuity of light perception. Because of a time delay in arranging a pars plana vitrectomy (PPV), the patient was treated with a prompt vitreous tap for culture an injection of vancomycin and ceftazidime. Four hours later, the PPV was performed and additional antibiotics were injected. The cultures from both the initial needle tap and the subsequent PPV isolated methicillin-resistant Staphylococcus epidermidis sensitive to vancomycin, but resistant to fourth-generation fluoroquinolones. The patient eventually recovered a visual acuity of 20/80 before developing retinal detachment. This case illustrates the time lag necessary to sterilize the vitreous cavity, and suggests a possible two-step staged treatment strategy for situations in which access to PPV equipment and support staff may be limited.Keywords: endophthalmitis, pars plana vitrectomy, tap and inject

Endophthalmitis following intravitreal injection is an infrequent but serious clinical problem. Infectious endophthalmitis must be differentiated from noninfectious inflammation. Depending on the series, the risk of endophthalmitis is very low. The use of a standardized injection protocol can reduce the risk of infection.

Diabetic macular edema remains an important cause of vision loss among patients with diabetes mellitus. Improved control of blood pressure and blood sugar, as well as photocoagulation, are effectiv...

Pharmacogenomics is an evolving research discipline in medicine. Within ophthalmology, the earliest candidate gene investigations have studied primary and secondary open-angle glaucoma (OAG), as well as normal tension glaucoma (NTG). At this time, pharmacogenomics data are not generally used to make clinical decisions. However, as we collect data from clinical trials, the role of pharmacogenomics in the care of patients with glaucoma and allied diseases will become clearer. There are at least two potential future roles for applying pharmacogenomics in the treatment of OAG and allied disorders. First, more targeted therapy may lead to better treatment outcomes, with less exposure to medications in patients unlikely to respond to them. Second, pharmacogenomic research may lead to the development of novel therapies for these diseases.

Elevation of intraocular pressure (IOP) following injection of intravitreal triamcinolone acetonide (IVTA) is an important clinical problem. The etiology of the steroid response is poorly understood, although a genetic determinant has long been suspected. We performed a pharmacogenomic association study with glucocorticoid receptor polymorphisms.Fifty-two patients (56 eyes) who underwent treatment with IVTA for various retinal diseases were genotyped for six well-studied glucocorticoid receptor polymorphisms (ER22/23EK, N363S, BclI, N766N, and single nucleotide polymorphisms (SNPs) within introns 3 and 4).Three polymorphisms (ER22/23EK, N363S, and the intron 3 SNP) were essentially nonpolymorphic within this population sample and excluded from further analysis. The remaining three polymorphisms (BclI, N766N, and within intron 4) passed the Hardy-Weinberg Equilibrium test, indicating good genotyping quality and normal population distribution of allelic frequency. No statistically significant correlations were found between these three polymorphisms and magnitude of IOP elevation following IVTA, using single point association and haplotype analyses.In this small, pilot study, we found no statistically significant relationship between glucocorticoid receptor polymorphisms and IOP elevation following IVTA. The precise etiology of the steroid response remains obscure. To our knowledge, this is the first published pharmacogenomic study of this common clinical entity.

Stephen G Schwartz, Harry W Flynn JrDepartment of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USAAbstract: Pars plana vitrectomy (PPV) is growing in popularity for the treatment of primary rhegmatogenous retinal detachment (RD). PPV achieves favorable anatomic and visual outcomes in a wide variety of patients, especially in pseudophakic RD. A growing number of clinical series, both retrospective and prospective, have demonstrated generally comparable outcomes comparing PPV and scleral buckling (SB) under a variety of circumstances. The Scleral Buckling Versus Primary Vitrectomy in Rhegmatogenous Retinal Detachment (SPR) study is a multicenter, randomized, prospective, controlled clinical trial comparing SB versus PPV. This study should provide useful guidelines in the future. At this time, the choice of SB versus PPV should be based on the characteristics of the RD, the patient as a whole, and the experience and preference of the individual retinal surgeon.Keywords: pars plana vitrectomy, rhegmatogneous retinal detachment, scleral buckling

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.

Acute-onset postoperative endophthalmitis is an uncommon but potentially severe complication of intraocular surgery. Acute-onset postoperative endophthalmitis is a clinical diagnosis, which is then confirmed by culture of vitreous or aqueous. The Endophthalmitis Vitrectomy Study (EVS) provided valuable treatment guidelines which are still relevant today. However, visual outcomes are frequently poor, even after prompt and appropriate treatment. Endophthalmitis cannot be completely prevented, but its incidence can be significantly reduced with the use of preoperative povidone-iodine antisepsis and attention to risk factors. Intracameral antibiotics are gaining in popularity, especially in Europe, although their efficacy is controversial.

Endophthalmitis remains an important cause of visual morbidity, even with appropriate and prompt treatment. Infectious endophthalmitis may be categorized by the cause of the infection and the characteristic timing of clinical symptoms and signs. The differential diagnosis includes noninfectious inflammation, such as toxic anterior segment syndrome, as well as pseudohypopyon composed of triamcinolone acetonide or dehemoglobinized intraocular hemorrhage. Two relatively newly appreciated categories of endophthalmitis that are becoming more prevalent are endophthalmitis associated with microbial keratitis and endophthalmitis following intravitreal injection. The Endophthalmitis Vitrectomy Study provides useful guidelines for the management of endophthalmitis. Prompt administration of antimicrobials is usually associated with better visual outcome making early diagnosis important. Advances in the management and prevention of endophthalmitis will probably come from improved antibiotic coverage, more effective r...

Clinical risk factors for diabetic retinopathy (DR), such as duration of disease and degree of glucose control, do not adequately predict disease progression in individual patients, suggesting the presence of a genetic component. Multiple smaller studies have investigated genotype-phenotype correlations in genes encoding vascular endothelial growth factor, aldose reductase, the receptor for advanced glycation end products, and many others. In general, reported results have been conflicting, due to factors including small sample sizes, variations in study design, differences in clinical end points, and underlying genetic differences between study groups. At this time, there is no confirmed association with any risk allele reported. As we continue to collect data from additional studies, the role of genetics in DR may become more apparent.

Rhegmatogenous retinal detachment (RRD) is a common clinical challenge that affects up to one of every 170 people.1 RRD treatment is one of the most common indications for vitreoretinal surgery, and such repair is one of the most cost-effective practices in the treatment of all vitreoretinal disorders.2–4 Retinal reattachment surgery is unusual among ophthalmic surgeries because excellent outcomes may be obtained using three distinct approaches: scleral buckling (SB) first described in the 1950s,5–7 pars plana vitrectomy (PPV) first reported in 19718 and pneumatic retinopexy (PR) first reported in 1986.9 Core surgical principles for RRD management include identification and treatment of all retinal breaks.10 PPV is increasingly employed in the repair of primary RRD. A 2012 US Medicare claims database analysis reported 74%, 11% and 15% of primary RRD being repaired with PPV, SB and PR, respectively,11 with substantial regional differences. Given the expansion of PPV use, vitreoretinal fellows are being exposed to fewer SB procedures. In a 2010 survey of 66% of USA vitreoretinal fellows, it was reported that 39% performed

To evaluate rates of reoperation and retinal detachment (RD) after macular hole surgery.Retrospective cross-sectional study.Patients in the insurance claim-based MarketScan databases from 2007 through 2013 with a record of macular hole surgery.Patients with macular hole surgery were identified. Cases of definite (the same eye was coded both times) and presumed (the eye laterality was not coded) macular hole reoperations within 2, 3, and 12 months were queried. In addition, cases of postoperative RD within 2, 3, and 12 months were captured.Rates of macular hole reoperation and postoperative RD, including subgroup analysis based on presence or absence of internal limiting membrane (ILM) peeling.Records of 23465 macular hole surgeries among 20 764 patients were analyzed. Among presumed reoperations, the rates of reoperation were 4.3% (4.1% after ILM peeling and 5.0% after no ILM peeling; P = 0.01) within 2 months of surgery, 5.5% (5.3% after ILM peeling and 6.2% after no ILM peeling; P = 0.03) within 3 months of surgery, and 9.5% (9.0% after ILM peeling and 11.0% after no ILM peeling; P = 0.01) within 12 months of surgery. The rates for definite reoperations were 1.3% (1.2% after ILM peeling and 1.8% after no ILM peeling; P = 0.04) at 2 months, 1.7% (1.6% after ILM peeling and 2.5% after no ILM peeling; P = 0.004) at 3 months, and 4.1% (3.3% after ILM peeling and 7.5% after no ILM peeling; P0.001) at 12 months. The cumulative rate of postoperative RD was 1.81±0.09% to 2.18±0.5% after 2 months, 2.27±0.10% to 3.18±0.67% after 3 months, and 3.92±0.16% to 5.70±1.1% after 12 months. Internal limiting membrane peeling was associated negatively with postoperative RD at 2 months (2.3% vs. 1.7%; P = 0.007), 3 months (2.8% vs. 2.1%; P = 0.004), and 12 months (4.7% vs. 3.3%; P0.001).In this sample, reoperations for macular hole were performed at low rates. Internal limiting membrane peeling was associated with lower rates of reoperation and RD.

Endophthalmitis following intravitreal injection is uncommon. There are currently no randomized clinical trials evaluating the role of prophylactic topical antibiotics in this setting. Many large series have reported that topical antibiotics do not decrease, and may in fact increase the rate of endophthalmitis. The reason for this apparent paradoxical finding is unknown but may be due to changes in conjunctival flora due to repeated exposure to antibiotics. At this time, antiseptics (specifically povidone-iodine), rather than antibiotics, are preferred for the majority of patients undergoing intravitreal injections.

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.

Glaucoma is a leading cause of irreversible blindness, presently affecting approximately 70 million people worldwide.1,2 The most common form is primary open-angle glaucoma (POAG), which accounts for approximately 90% of all cases. Ocular hypertension (OH) is the major risk factor for POAG and lowering IOP is the only effective treatment.3 However, many patients remain refractory to existing IOP-lowering interventions and eventually may become blind, underscoring the unmet medical need for novel approaches to control IOP. Intraocular pressure is a product of the rate of aqueous humor production, resistance to outflow, and episcleral venous pressure.3,4 The aqueous outflow pathways in the angle of the eye are composed of a spongy tissue called the trabecular meshwork (TBM), which leads into Schlemm's canal. Much of the resistance to outflow resides within the TBM, putatively within 7 to 14 μm of the inner wall of Schlemm's canal in a region known as the juxtacanalicular or cribriform region.5–,8 Primary open-angle glaucoma is caused by an increase in outflow resistance9,10 due to poorly understood defects in this region.11–,14 Ocular hypertension in POAG has been associated with dysregulated intracellular signaling pathways controlled by IL-1/NF-κB,15 TGF-β superfamily,16 and Wnt.17,18 The pathophysiology of OH leading to POAG shares many features with a secondary form of OH caused by treatment with glucocorticoids (GCs).19–,25 Glucocorticoids are a class of steroid hormones released in response to stress. As part of the natural feedback mechanism that turns down the inflammatory response, they are useful for treating a wide variety of diseases.26 Complicating this, however, is the considerable interindividual variability and tissue-specific GC sensitivity among individuals, which can cause a variety of systemic side effects.27–,31 Treatment with steroids, such as dexamethasone or triamcinolone acetonide (TA), in the eye causes elevated IOP in predisposed individuals. It has been documented that approximately 40% of the normal population develops an IOP increase > 6 mm Hg above baseline following topical administration of GCs, 4 times a day for 4 to 6 weeks.32 When GCs are administered intravitreally, IOP may increase by 30% or more in up to half of patients.33 These individuals are considered to be “steroid responders.” Interestingly, almost all POAG patients are steroid responders25,32,34–,40; conversely, steroid-responders who do not have POAG are at much higher risk of developing POAG compared to nonresponders.37–,41 A better understanding of genetic and molecular mechanisms underlying individual variation in the response to steroids could shed light on our understanding of steroid-induced OH and OH leading to POAG. That being said, mechanisms of steroid-induced OH and OH leading to POAG also show distinct differences; therefore, studying the genetics of steroid-induced OH specifically could lead to discovery of genes involved in IOP regulation that could not have been revealed any other way. The genome-wide association study (GWAS) represents an agnostic approach for prioritization of genes that are associated with a disease process, and makes it possible to discover novel genes that could not otherwise be identified. In the current study, we performed a pharmaco-GWAS for this purpose, using a cohort enrolled from patients treated with off-label intravitreal TA (IVTA) for various retinal indications, and followed up with an independent candidate gene study. We identified two independent quantitative trait loci (QTLs) at chromosomal locus 6p21.33 associated with the novel mucin gene HCG22.

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.]

Endophthalmitis remains a rare but serious cause of visual loss. Over time, changes have been noted in endophthalmitis in terms of predominant causes, infecting organisms, and antibiotic susceptibilities. There is controversy regarding the use of intracameral prophylactic antimicrobials during cataract surgery. Alternatively, there appears to be increasing evidence against using routine topical antibiotics for intravitreal injections. There are also increasing reports of multidrug-resistant organisms causing endophthalmitis, but the combination of vancomycin and ceftazidime appears effective for the vast majority of cases. Future trends may involve increasing utilization of polymerase chain reaction for diagnosis, and possibly office-based pars plana vitrectomy for treatment of endophthalmitis.

Diabetic macular edema (DME) is the most common cause of visual impairment due to diabetic retinopathy. The treatment of DME has recently undergone a paradigm shift. Traditionally, photocoagulation was standard treatment, but pharmacologic therapies are becoming increasingly used for this purpose. All currently available drug therapies for DME are either anti-VEGF agents or corticosteroids.The pathogenesis of DME involves angiogenesis, inflammation and oxidative stress. The scientific rationale to treat DME through the pharmacologic blockade of VEGF and other pro-angiogenic factors is discussed. The fluocinolone insert is approved for the treatment of DME in several European countries, but not in the US at this time. Some medications that are already approved for other retinal diseases, most prominently aflibercept and the dexamethasone delivery system, have recently obtained approval for DME in the US. Other compounds are being studied in earlier-phase clinical trials.Pharmacologic treatment of DME will likely become increasingly used, especially for patients with edema involving the fovea. At this time, the two main classes of medication for treatment of DME are anti-VEGF agents and corticosteroids. As we continue to collect clinical trials data, the precise role of individual agents, and the continuing role for photocoagulation, will become more clear.

We tried to identify the earliest cataract surgeons in the English-speaking areas of America. In 1751, couching was performed on the Caribbean island of Montserrat by John Morphy. William Stork of England, who couched cataracts, practiced in Jamaica in 1760 and then in cities from Annapolis to Boston between 1761 and 1764. Frederick William Jericho of Germany, upon completion of his training at Utrecht, published his 1767 treatise on his preferred surgical technique of extracapsular cataract extraction. Jericho had practiced in the Leeward Islands by 1776 and then in cities from Charleston to Boston between 1783 and 1785. The French surgeon Lewis Leprilete was the first to advertise cataract extraction in the United States in 1782 and probably passed on the skill to his protégé, Nathaniel Miller of Massachusetts. Leprilete was also the first to publicize Benjamin Franklin's invention of bifocals.. These pioneers exposed American doctors and the public to cataract surgery. Shortly after their arrival, evidence emerges of other surgeons performing these procedures in America.

From antiquity through the Renaissance, congenital blindness was generally regarded as incurable, as noted in both medical and lay publications. The earliest reference to congenital cataract surgery that we identified, reported in 1663, referred to an 18-year-old female treated by English oculist John Stepkins (d. 1652). An examination of the literature related to the Stepkins family reveals the presence of male and female oculists during that period, including his daughter, Lady Theodosia Ivy. Eye waters attributed to Stepkins contained tutty (an oxide of zinc), roses, sugar candy, and other ingredients. Interestingly, John Thomas Woolhouse, the author of the next identified report of congenital cataract surgery in 1706, stated that he was related to Stepkins. Woolhouse reported by 1721 that he had performed 36 congenital cataract surgeries, with the youngest patient being 18 months of age.

Schizophrenia is associated with deficits in higher-order processing of visual information. This study evaluated the integrity of early visual processing in order to evaluate the overall pattern of visual dysfunction in schizophrenia.Steady-state visual-evoked potential responses were recorded over the occipital cortex in patients with schizophrenia and in age- and sex-matched comparison volunteers. Visual-evoked potentials were obtained for stimuli composed of isolated squares that were modulated sinusoidally in luminance contrast, number of squares, or chromatic contrast in order to emphasize magnocellular or parvocellular visual pathway activity.Responses of patients to magnocellular-biased stimuli were significantly lower than those of comparison volunteers. These lower response levels were observed in conditions using both low luminance contrast and large squares that biased processing toward the magnocellular pathway. In contrast, responses to stimuli that biased processing toward the parvocellular pathway were not significantly different between schizophrenia patients and comparison volunteers. A significant interaction of group and stimulus type was observed in the condition using low luminance contrast.These findings suggest a dysfunction of lower-level visual pathways, which was more prominent for magnocellular than parvocellular biased stimuli. The magnocellular pathway helps in orienting toward salient stimuli. A magnocellular pathway deficit could contribute to higher-level visual cognitive deficits in schizophrenia.

BACKGROUND: Retinitis pigmentosa (RP) comprises a group of hereditary eye diseases characterized by progressive degeneration of retinal photoreceptors. It results in severe visual loss that may lead to blindness. Symptoms may become manifest during childhood or adulthood which include poor night vision (nyctalopia) and constriction of peripheral vision (visual field loss). Visual field loss is progressive and affects central vision later in the disease course. The worldwide prevalence of RP is approximately 1 in 4000, with 100,000 individuals affected in the USA. At this time, there is no proven therapy for RP. OBJECTIVES: The objective of this review was to synthesize the best available evidence regarding the effectiveness and safety of vitamin A and fish oils (docosahexaenoic acid (DHA)) in preventing the progression of RP. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Trials Register (2020, Issue 2); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov; the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP); and OpenGrey. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 7 February 2020. SELECTION CRITERIA: We included randomized controlled trials that enrolled participants of any age diagnosed with any degree of severity or type of RP, and evaluated the effectiveness of vitamin A, fish oils (DHA), or both compared to placebo, vitamins (other than vitamin A), or no therapy, as a treatment for RP. We excluded cluster‐randomized trials and cross‐over trials. DATA COLLECTION AND ANALYSIS: We prespecified the following outcomes: mean change from baseline visual field, mean change from baseline electroretinogram (ERG) amplitudes, and anatomic changes as measured by optical coherence tomography (OCT), at one‐year follow‐up, and mean change in visual acuity, at five‐year follow‐up. Two review authors independently extracted data and evaluated risk of bias for all included trials. We also contacted study investigators for further information when necessary. MAIN RESULTS: In addition to three trials from the previous version of this review, we included a total of four trials with 944 participants aged 4 to 55 years. Two trials included only participants with X‐linked RP and the other two included participants with RP of all forms of genetic predisposition. Two trials evaluated the effect of DHA alone; one trial evaluated vitamin A alone; and one trial evaluated DHA and vitamin A versus vitamin A alone. Two trials recruited participants from the USA, and the other two recruited from the USA and Canada. All trials were at low risk of bias for most domains. We did not perform meta‐analysis due to clinical heterogeneity. Four trials assessed visual field sensitivity. Investigators found no evidence of a difference in mean values between the groups. However, one trial found that the annual rate of change of visual field sensitivity over four years favored the DHA group in foveal (−0.02 ± 0.55 (standard error (SE)) dB versus −0.47 ± 0.03 dB, P = 0.039), macular (−0.42 ± 0.05 dB versus −0.85 ± 0.03 dB, P = 0.031), peripheral (−0.39 ± 0.02 versus −0.86 ± 0.02 dB, P < 0.001), and total visual field sensitivity (−0.39 ± 0.02 versus −0.86 ± 0.02 dB, P < 0.001). The certainty of the evidence was very low. The four trials evaluated visual acuity (LogMAR scale) at a follow‐up of four to six years. In one trial (208 participants), investigators found no evidence of a difference between the two groups, as both groups lost 0.7 letters of the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity per year. In another trial (41 participants), DHA showed no evidence of effect on visual acuity (mean difference −0.01 logMAR units (95% confidence interval −0.14 to 0.12; one letter difference between the two groups; very low‐certainty evidence). In the third trial (60 participants), annual change in mean number of letters correct was −0.8 (DHA) and 1.4 letters (placebo), with no evidence of between‐group difference. In the fourth trial (572 participants), which evaluated (vitamin A + vitamin E trace) compared with (vitamin A trace + vitamin E trace), decline in ETDRS visual acuity was 1.1 versus 0.9 letters per year, respectively. All four trials reported electroretinography (ERG). Investigators of two trials found no evidence of a difference between the DHA and placebo group in yearly rates of change in 31 Hz cone ERG amplitude (mean ± SE) (−0.028 ± 0.001 log μV versus −0.022 ± 0.002 log μV; P = 0.30); rod ERG amplitude (mean ± SE) (−0.010 ± 0.001 log μV versus −0.023 ± 0.001 log μV; P = 0.27); and maximal ERG amplitude (mean ± SE) (−0.042 ± 0.001 log μV versus −0.036 ± 0.001 log μV; P = 0.65). In another trial, a slight difference (6.1% versus 7.1%) in decline of ERG per year favored vitamin A (P = 0.01). The certainty of the evidence was very low. One trial (51 participants) that assessed optical coherence tomography found no evidence of a difference in ellipsoid zone constriction (P = 0.87) over two years, with very low‐certainty evidence. The other three trials did not report this outcome. Only one trial reported adverse events, which found that 27/60 participants experienced 42 treatment‐related emergent adverse events (22 in DHA group, 20 in placebo group). The certainty of evidence was very low. The rest of the trials reported no adverse events, and no study reported any evidence of benefit of vitamin supplementation on the progression of visual acuity loss. AUTHORS' CONCLUSIONS: Based on the results of four studies, it is uncertain if there is a benefit of treatment with vitamin A or DHA, or both for people with RP. Future trials should also take into account the changes observed in ERG amplitudes and other outcome measures from trials included in this review.

The use of anti-vascular endothelial growth factor (VEGF) agents has led to a dramatic increase in the number of intravitreal injections. Endophthalmitis remains a rare but potentially vision-threatening complication of intravitreal injections. Recent large series have estimated this risk to be about one in 3,000 injections or less. Bevacizumab, which is generally prepared by a compounding pharmacy, is associated with additional risks of contamination. Although endophthalmitis cannot be prevented in all cases, certain risk reduction strategies have been proposed, including the use of an eyelid speculum, povidone iodine, avoidance of needle contact with the eyelid margin or eyelashes, and avoidance of routine post-injection antibiotics. Despite these precautions, some patients will develop endophthalmitis following intravitreal anti-VEGF injections, and outcomes may be poor despite prompt and appropriate therapy.

Torpedo maculopathy is a congenital solitary, oval-shaped lesion typically located temporal to the center of the macula. Congenital hypertrophy of the retinal pigment epithelium (RPE), RPE lesions of Gardner syndrome, and other lesions can present with similar characteristics. Because of its unique clinical and imaging features, torpedo maculopathy generally can be differentiated from other posterior segment lesions. [ Ophthalmic Surg Lasers Imaging Retina . 2014;45:222–226.]