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PURPOSE: To describe a syndrome of hemorrhagic occlusive retinal vasculitis (HORV) that developed after seemingly uncomplicated cataract surgery. DESIGN: Retrospective case series. SUBJECTS: Eleven eyes of 6 patients from 6 different institutions. METHODS: Cases were identified after discussion among retina specialists. The findings on presentation, clinical course, and outcome of a series of 7 eyes of 4 patients were compared with a previous report of 4 eyes of 2 patients, and data from both series were combined for a comprehensive analysis. MAIN OUTCOME MEASURES: Historical data, examination findings, imaging results, systemic evaluation findings, treatment regimens, and visual outcomes. RESULTS: Eleven eyes of 6 patients underwent otherwise uncomplicated cataract surgery, receiving viscoelastic and prophylactic intracameral vancomycin during the procedure. Despite good initial vision on postoperative day 1, between 1 to 14 days after surgery, all eyes demonstrated painless vision loss resulting from HORV. Extensive ocular and systemic evaluations were unrevealing in all patients. All patients were treated with aggressive systemic and topical corticosteroids. Additional treatments included systemic antiviral medication in 4 patients, intravitreal antibiotics in 4 eyes, and pars plana vitrectomy in 4 eyes. Skin testing for vancomycin sensitivity showed negative results in 3 patients and was not performed in the others. Neovascular glaucoma developed in 7 eyes, and all eyes received intravitreal anti-vascular endothelial growth factor (VEGF) injection, panretinal photocoagulation, or both for retinal ischemia. Final visual acuity was less than 20/100 in 8 of 11 eyes. CONCLUSIONS: Postoperative HORV is an exceedingly rare and potentially devastating condition that can occur after otherwise uncomplicated cataract surgery. Although the precise cause remains unknown, this disease may represent a delayed immune reaction similar to vancomycin-induced leukocytoclastic vasculitis. Despite treatment with high-dose corticosteroids, antiviral medication, and early vitrectomy in many patients, visual outcomes typically were poor in this series. Early intervention with intravitreal anti-VEGF medication and panretinal photocoagulation may help to prevent additional vision loss resulting from neovascular glaucoma.

PURPOSE: To report the technique and result of keratopigmentation using a femtosecond laser for the treatment of functional visual disabilities caused by peripheral iridectomies. DESIGN: Case report. METHODS: Two eyes of 2 patients underwent femtosecond laser-assisted keratopigmentation (FLAK) for moderate to severe visual dysfunction secondary to peripheral iridectomies. The main outcomes measures of the study were changes in visual-related symptoms, cosmesis, and intraoperative surgical complications. RESULTS: Following FLAK, the visual-related symptoms (ghosting, glare, and monocular diplopia) improved in both cases with significant improvement to total elimination of symptoms. No patient lost any lines of visual acuity, and no significant complications were observed during the follow-up period. The cosmetic appearance was reported as very good. CONCLUSIONS: FLAK is minimally invasive and results in a significant decrease in the subjective glare and photophobia and even in resolution of monocular diplopia. The cosmetic outcome was also favorable. This technique allows surgeons to correct visual disabilities associated with iris defects with a high success rate while avoiding more aggressive intraocular surgery.

The field of gene therapy for retinal blinding disorders is experiencing incredible momentum, justified by hopeful results in early stage clinical trials for inherited retinal degenerations. The premise of the use of the gene as a drug has come a long way, and may have found its niche in the treatment of retinal disease. Indeed, with only limited treatment options available for retinal indications, gene therapy has been proven feasible, safe, and effective and may lead to durable effects following a single injection. Here, we aim at putting into context the promise and potential, the technical, clinical, and economic boundaries limiting its application and development, and speculate on a future in which gene therapy is an integral component of ophthalmic clinical care.

IMPORTANCE: To facilitate comparative clinical outcome research in low vision rehabilitation, we must use patient-centered measurements that reflect clinically meaningful changes in visual ability. OBJECTIVE: To quantify the effects of currently provided low vision rehabilitation (LVR) on patients who present for outpatient LVR services in the United States. DESIGN, SETTING, AND PARTICIPANTS: Prospective, observational study of new patients seeking outpatient LVR services. From April 2008 through May 2011, 779 patients from 28 clinical centers in the United States were enrolled in the Low Vision Rehabilitation Outcomes Study. The Activity Inventory, a visual function questionnaire, was administered to measure overall visual ability and visual ability in 4 functional domains (reading, mobility, visual motor function, and visual information processing) at baseline and 6 to 9 months after usual LVR care. The Geriatric Depression Scale, Telephone Interview for Cognitive Status, and Medical Outcomes Study 36-Item Short-Form Health Survey physical functioning questionnaires were also administered to measure patients' psychological, cognitive, and physical health states, respectively, and clinical findings of patients were provided by study centers. MAIN OUTCOMES AND MEASURES: Mean changes in the study population and minimum clinically important differences in the individual in overall visual ability and in visual ability in 4 functional domains as measured by the Activity Inventory. RESULTS: Baseline and post-rehabilitation measures were obtained for 468 patients. Minimum clinically important differences (95% CIs) were observed in nearly half (47% [95% CI, 44%-50%]) of patients in overall visual ability. The prevalence rates of patients with minimum clinically important differences in visual ability in functional domains were reading (44% [95% CI, 42%-48%]), visual motor function (38% [95% CI, 36%-42%]), visual information processing (33% [95% CI, 31%-37%]), and mobility (27% [95% CI, 25%-31%]). The largest average effect size (Cohen d = 0.87) for the population was observed in overall visual ability. Age (P = .006) was an independent predictor of changes in overall visual ability, and logMAR visual acuity (P = .002) was predictive of changes in visual information processing. CONCLUSIONS AND RELEVANCE: Forty-four to fifty percent of patients presenting for outpatient LVR show clinically meaningful differences in overall visual ability after LVR, and the average effect sizes in overall visual ability are large, close to 1 SD.

PURPOSE: Retinitis pigmentosa is a Mendelian disease with a very elevated genetic heterogeneity. Most mutations are responsible for less than 1% of cases, making molecular diagnosis a multigene screening procedure. In this study, we assessed whether direct testing of specific alleles could be a valuable screening approach in cases characterized by prevalent founder mutations. METHODS: We screened 275 North American patients with recessive/isolate retinitis pigmentosa for two mutations: an Alu insertion in the MAK gene and the p.Lys42Glu missense in the DHDDS gene. All patients were unrelated; 35 reported Jewish ancestry and the remainder reported mixed ethnicity. RESULTS: We identified the MAK and DHDDS mutations homozygously in only 2.1% and 0.8%, respectively, of patients of mixed ethnicity, but in 25.7% and 8.6%, respectively, of cases reporting Jewish ancestry. Haplotype analyses revealed that inheritance of the MAK mutation was attributable to a founder effect. CONCLUSION: In contrast to most mutations associated with retinitis pigmentosa-which are, in general, extremely rare-the two alleles investigated here cause disease in approximately one-third of North American patients reporting Jewish ancestry. Therefore, their screening constitutes an alternative procedure to large-scale tests for patients belonging to this ethnic group, especially in time-sensitive situations.Genet Med 17 4, 285-290.

BACKGROUND: Graft failure because of immune rejection remains a significant problem in organ transplantation, and lymphatic and blood vessels are important components of the afferent and efferent arms of the host alloimmune response, respectively. We compare the effect of antihemangiogenic and antilymphangiogenic therapies on alloimmunity and graft survival in a murine model of high-risk corneal transplantation. METHODS: Orthotopic corneal transplantation was performed in hemevascularized and lymph-vascularized high-risk host beds, and graft recipients received subconjunctival vascular endothelial growth factor (VEGF)-trap, anti-VEGF-C, sVEGFR-3, or no treatment, beginning at the time of surgery. Fourteen days after transplantation, graft hemeangiogenesis and lymphangiogenesis were evaluated by immunohistochemistry. The frequencies of Th1 cells in regional lymphoid tissue and graft-infiltrating immune cells were evaluated by flow cytometry. Long-term allograft survival was compared using Kaplan-Meier curves. RESULTS: VEGF-trap significantly decreased graft hemangiogenesis as compared to the control group and was most effective in reducing the frequency of graft-infiltrating immune cells. Anti-VEGF-C and sVEGFR3 significantly decreased graft lymphangiogenesis and lymphoid Th1 cell frequencies as compared to control. VEGF-trap (72%), anti-VEGF-C (25%), and sVEGFR-3 (11%) all significantly improved in the 8-week graft survival compared to control (0%), although VEGF-trap was significantly more effective than both anti-VEGF-C (P < 0.05) and sVEGFR-3 (P < 0.05). CONCLUSION: In a clinically relevant model of high-risk corneal transplantation in which blood and lymphatic vessels are present and treatment begins at the time of transplantation, VEGF-trap is significantly more effective in improving long-term graft survival as compared to anti-VEGF-C and sVEGFR-3, but all approaches improve survival when compared to untreated control.

BACKGROUND/AIMS: To evaluate ex vivo biomechanical and enzymatic digestion resistance differences between standard myopic laser in-situ keratomileusis (LASIK) compared with LASIK+CXL, in which high-irradiance cross-linking (CXL) is added. METHODS: Eight human donor corneas were subjected to femtosecond-assisted myopic LASIK. Group A (n=4) served as a control group (no CXL). The corneas in LASIK+CXL group B were subjected to concurrent prophylactic high-irradiance CXL (n=4). Saline-diluted (0.10%) riboflavin was instilled on the stroma, subsequently irradiated with UV-A through the repositioned flap. The cornea stroma and flap specimens were separately subjected to transverse biaxial resistance measurements; biomechanical differences were assessed via stress and Young's shear modulus. Subsequently, the specimens were subjected to enzymatic degradation. RESULTS: For the corneal stroma specimen, stress at 10% strain was 128±11 kPa for control group A versus 293±20 kPa for the LASIK+CXL group B (relative difference Δ=+129%, p<0.05). The stress in group B was also increased at 20% strain by +68% (p<0.05). Shear modulus in group B was increased at 10% strain by +79%, and at 20% strain by +48% (both statistically significant, p<0.05). The enzymatic degradation time to dissolution was 157.5±15.0 min in group A versus 186.25±7.5 min in group B (Δ=+18%, p=0.014). For the flaps, both biomechanical, as well as enzymatic degradation tests showed no significant differences. CONCLUSIONS: LASIK+CXL appears to provide significant increase in underlying corneal stromal rigidity, up to +130%. Additionally, there is significant relevant enzymatic digestion resistance confirmatory to the above. LASIK flaps appear unaffected biomechanically by the LASIK+CXL procedure, suggesting effective CXL just under the flap.

The paucity of animal models exhibiting full pathology of diabetic retinopathy (DR) has impeded understanding of the pathogenesis of DR and the development of therapeutic interventions. Here we investigated if hyperhexosemic marmosets (Callithrix jacchus) develop characteristic retinal vascular lesions including macular edema (ME), a leading cause of vision loss in DR. Marmosets maintained on 30% galactose (gal)-rich diet for two years were monitored for retinal vascular permeability, development of ME, and morphological characteristics including acellular capillaries (AC) and pericyte loss (PL), vessel tortuosity, and capillary basement membrane (BM) thickness. Excess vascular permeability, increased number of AC and PL, vascular BM thickening, and increased vessel tortuosity were observed in the retinas of gal-fed marmosets. Optical coherence tomography (OCT) images revealed significant thickening of the retinal foveal and the juxtafoveal area, and histological analysis showed incipient microaneurysms in retinas of gal-fed marmosets. Findings from this study indicate that hyperhexosemia can trigger retinal vascular changes similar to those seen in human DR including ME and microaneurysms. The striking similarities between the marmoset retina and the human retina, and the exceptionally small size of the monkey, offer significant advantages to this primate model of DR.

PURPOSE: To report the prevalence and risk factors for retinopathy in African Americans with impaired fasting glucose (IFG) and type 2 diabetes in the Jackson Heart Study and to determine if P-selectin plasma levels are independently associated with retinopathy in this population. DESIGN: Prospective, cross-sectional observational study. METHODS: setting: Community-based epidemiologic study. STUDY POPULATION: Total of 629 patients with type 2 diabetes and 266 participants with impaired fasting glucose. OBSERVATION PROCEDURES: Bilateral, 7-field fundus photographs were scored by masked readers for diabetic retinopathy (DR) level. Covariate data including P-selectin plasma levels and genotypes were collected in a standardized fashion. MAIN OUTCOME MEASURES: Association between risk factors, including P-selectin plasma levels and genotypes, and retinopathy. RESULTS: The prevalences of any retinopathy among participants with IFG and type 2 diabetes were 9.4% and 32.4%, respectively. Among those with type 2 diabetes, in multivariate models adjusted for age, sex, and other traditional risk factors, higher P-selectin levels were associated with any DR (odds ratio = 1.11, 95% confidence interval = 1.02-1.21, P = .02) and proliferative DR (odds ratio = 1.23, 95% confidence interval = 1.03-1.46, P = .02). To further investigate the relationship between P-selectin and DR, we examined the association between P-selectin genotype and DR. Minor allele homozygotes for the variant rs6128 were less likely to develop DR (P after Bonferroni correction = 0.03). CONCLUSIONS: Both serologic and genetic data show an association between P-selectin and DR in the Jackson Heart Study. If confirmed in other studies, this association may provide insight into the pathogenesis of retinopathy.

BACKGROUND: Retinopathy of prematurity (ROP) is a vision-threatening disease in premature infants. Serum adiponectin (APN) concentrations positively correlate with postnatal growth and gestational age, important risk factors for ROP development. Dietary ω-3 (n-3) long-chain polyunsaturated fatty acids (ω-3 LCPUFAs) suppress ROP and oxygen-induced retinopathy (OIR) in a mouse model of human ROP, but the mechanism is not fully understood. OBJECTIVE: We examined the role of APN in ROP development and whether circulating APN concentrations are increased by dietary ω-3 LCPUFAs to mediate the protective effect in ROP. DESIGN: Serum APN concentrations were correlated with ROP development and serum ω-3 LCPUFA concentrations in preterm infants. Mouse OIR was then used to determine whether ω-3 LCPUFA supplementation increases serum APN concentrations, which then suppress retinopathy. RESULTS: We found that in preterm infants, low serum APN concentrations positively correlate with ROP, and serum APN concentrations positively correlate with serum ω-3 LCPUFA concentrations. In mouse OIR, serum total APN and bioactive high-molecular-weight APN concentrations are increased by ω-3 LCPUFA feed. White adipose tissue, where APN is produced and assembled in the endoplasmic reticulum, is the major source of serum APN. In mouse OIR, adipose endoplasmic reticulum stress is increased, and APN production is suppressed. ω-3 LCPUFA feed in mice increases APN production by reducing adipose endoplasmic reticulum stress markers. Dietary ω-3 LCPUFA suppression of neovascularization is reduced from 70% to 10% with APN deficiency. APN receptors localize in the retina, particularly to pathologic neovessels. CONCLUSION: Our findings suggest that increasing APN by ω-3 LCPUFA supplementation in total parental nutrition for preterm infants may suppress ROP.

The ability to form biofilms in a variety of environments is a common trait of bacteria, and may represent one of the earliest defenses against predation. Biofilms are multicellular communities usually held together by a polymeric matrix, ranging from capsular material to cell lysate. In a structure that imposes diffusion limits, environmental microgradients arise to which individual bacteria adapt their physiologies, resulting in the gamut of physiological diversity. Additionally, the proximity of cells within the biofilm creates the opportunity for coordinated behaviors through cell-cell communication using diffusible signals, the most well documented being quorum sensing. Biofilms form on abiotic or biotic surfaces, and because of that are associated with a large proportion of human infections. Biofilm formation imposes a limitation on the uses and design of ocular devices, such as intraocular lenses, posterior contact lenses, scleral buckles, conjunctival plugs, lacrimal intubation devices and orbital implants. In the absence of abiotic materials, biofilms have been observed on the capsule, and in the corneal stroma. As the evidence for the involvement of microbial biofilms in many ocular infections has become compelling, developing new strategies to prevent their formation or to eradicate them at the site of infection, has become a priority.

PURPOSE: To report on the accuracy of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for identifying patients with polymyalgia rheumatica (PMR) and concurrent noninfectious inflammatory ocular conditions in a large healthcare organization database. METHODS: Queries for patients with PMR and uveitis or scleritis were executed in two general teaching hospitals' databases. Patients with ocular infections or other rheumatologic conditions were excluded. Patients with PMR and ocular inflammation were identified, and medical records were reviewed to confirm accuracy. RESULTS: The query identified 10,697 patients with the ICD-9-CM code for PMR and 4154 patients with the codes for noninfectious inflammatory ocular conditions. The number of patients with both PMR and noninfectious uveitis or scleritis by ICD-9-CM codes was 66. On detailed review of the charts of these 66 patients, 31 (47%) had a clinical diagnosis of PMR, 43 (65%) had noninfectious uveitis or scleritis, and only 20 (30%) had PMR with concurrent noninfectious uveitis or scleritis confirmed based on clinical notes. CONCLUSIONS: While the use of ICD-9-CM codes has been validated for medical research of common diseases, our results suggest that ICD-9-CM codes may be of limited value for epidemiological investigations of diseases which can be more difficult to diagnose. The ICD-9-CM codes for rarer diseases (PMR, uveitis and scleritis) did not reflect the true clinical problem in a large proportion of our patients. This is particularly true when coding is performed by physicians outside the area of specialty of the diagnosis.