FasL was recently shown be required for bacterial clearance in C57BL/6 mice that express the FasL.1 allotype. The FasL.2 allotype is expressed in BALB/c mice and exhibits increased binding affinity to and increased cytotoxic activity against Fas(+) target cells. Therefore, we hypothesized that BALB/c mice would be more resistant to Staphylococcus aureus-induced endophthalmitis. To test this hypothesis, C57BL/6, BALB/c, and BALB(gld) mice received intravitreal injections of 2,500 CFU of S. aureus (RN6390). Clinical examinations, electroretinography (ERG), histology, and bacterial quantification were performed at 24, 48, 72, and 96 h postinjection. The myeloperoxidase (MPO) assay was used to quantitate neutrophil infiltration. At 96 h postinfection, 86% of C57BL/6 mice presented with complete destruction of the eye, compared to only 29% of BALB/c mice with complete destruction. To our surprise, in the absence of Fas ligand, BALB(gld) mice showed no difference in bacterial clearance compared to BALB/c mice. However, histology and ERG analysis revealed increased retinal damage and significant loss of retinal function. MPO analysis revealed equal numbers of neutrophils in BALB(gld) and BALB/c mice at 24 h postinfection. However, at 48 h, the neutrophil numbers remained significantly elevated in BALB(gld) mice, correlating with the increased retinal damage observed in BALB(gld) mice. We conclude that the increased resistance to S. aureus induced endophthalmitis in BALB/c mice is not dependent upon the FasL. However, in contrast to C57BL/6 mice, FasL is required for resolution of inflammation and protecting host tissue from nonspecific damage in BALB/c mice.

PURPOSE: Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein known to regulate extracellular matrix (ECM) in many tissues and is highly expressed in trabecular meshwork (TM). SPARC-null mice have a 15% to 20% decrease in intraocular pressure (IOP) compared to wild-type (WT) mice. We hypothesized that mouse aqueous outflow is segmental, and that transgenic deletion of SPARC causes a more uniform pattern that correlates with IOP and TM morphology. METHODS: Eyes of C57BL6-SV129 WT and SPARC-null mice were injected with fluorescent microbeads, which were also passively exposed to freshly enucleated eyes. Confocal and electron microscopy were performed. Percentage effective filtration length (PEFL) was calculated as PEFL = FL/TL × 100%, where TL = total length and FL = filtration length. IOP was measured by rebound tonometry. RESULTS: Passive microbead affinity for WT and SPARC-null ECM did not differ. Segmental flow was observed in the mouse eye. SPARC-null mice had a 23% decrease in IOP. PEFL increased in SPARC-null (70.61 ± 11.36%) versus WT mice (54.68 ± 9.95%, P < 0.005; n = 11 pairs), and PEFL and IOP were negatively correlated (R(2) = 0.72, n = 10 pairs). Morphologically, TM of high-tracer regions had increased separation between beams compared to low-tracer regions. Collagen fibril diameter decreased in SPARC-null (28.272 nm) versus WT tissue (34.961 nm, P < 0.0005; n = 3 pairs). CONCLUSIONS: Aqueous outflow in mice is segmental. SPARC-null mice demonstrated a more uniform outflow pattern and decreased collagen fibril diameter. Areas of high flow had less compact juxtacanalicular connective tissue ECM, and IOP was inversely correlated with PEFL. Our data show a correlation between morphology, aqueous outflow, and IOP, indicating a modulatory role of SPARC in IOP regulation.

In this work we present the results of the cognitive impact evaluation regarding the use of Audiopolis, an audio and/or haptic-based videogame. The software has been designed, developed and evaluated for the purpose of developing orientation and mobility (O&M) skills in blind users. The videogame was evaluated through cognitive tasks performed by a sample of 12 learners. The results demonstrated that the use of Audiopolis had a positive impact on the development and use of O&M skills in school-aged blind learners.

Caveolin-1 is the primary structural component of endothelial caveolae that is essential for transcellular trafficking of albumin and is also a critical scaffolding protein that regulates the activity of signaling molecules in caveolae. Phosphorylation of caveolin-1 plays a fundamental role in the mechanism of oxidant-induced vascular hyper permeability. However, the regulatory mechanism of caveolin-1 phosphorylation remains unclear. Here we identify a previously unexpected role for AMPK in inhibition of caveolin-1 phosphorylation under oxidative stress. A pharmacological activator of AMPK, 5-amino-4-imidazole carboxamide riboside (AICAR), inhibited oxidative stress-induced phosphorylation of both caveolin-1 and c-Abl, which is the major kinase of caveolin-1, and endocytosis of albumin in human umbilical vein endothelial cell. These effects were abolished by treatment with two specific inhibitors of AICAR, dipyridamole, and 5-iodotubericidin. Consistently, knockdown of the catalytic AMPKα subunit by siRNA abolished the inhibitory effect of AICAR on oxidant-induced phosphorylation of both caveolin-1 and c-Abl. Pretreatment with specific c-Abl inhibitor, imatinib mesylate, and knock down of c-Abl significantly decreased the caveolin-1 phosphorylation after H2O2 exposure and abolished the inhibitory effect of AICAR on the caveolin-1 phosphorylation. Interestingly, knockdown of Prdx-1, an antioxidant enzyme associated with c-Abl, increased phosphorylation of both caveolin-1 and c-Abl and abolished the inhibitory effect of AICAR on the caveolin-1 phosphorylation. Furthermore, co-immunoprecipitation experiment showed that AICAR suppressed the oxidant-induced dissociation between c-Abl and Prdx1. Overall, our results suggest that activation of AMPK inhibits oxidative stress-induced caveolin-1 phosphorylation and endocytosis, and this effect is mediated in part by stabilizing the interaction between c-Abl and Prdx-1.

5-Aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR), an analog of AMP is widely used as an activator of AMP-kinase (AMPK), a protein that regulates the responses of the cell to energy change. Recently, we showed that AICAR-induced AMPK activation inhibits the growth of retinoblastoma cells in vitro by decreasing cyclins and by inducing apoptosis and S-phase arrest. In this study, we investigated the effects of AMPK activator AICAR on the growth of retinoblastoma in vivo. Intraperitoneal injection of AICAR resulted in 48% growth inhibition of Y79 retinoblastoma cell tumors in mice. Tumors isolated from mice treated with AICAR had decreased expression of Ki67 and increased apoptotic cells (TUNEL positive) compared with the control. In addition, AICAR treatment suppressed significantly tumor vessel density and macrophage infiltration. We also showed that AICAR administration resulted in AMPK activation and mTOR pathway inhibition. Paradoxically observed down-regulation of p21, which indicates that p21 may have a novel function of an oncogene in retinoblastoma tumor. Our results indicate that AICAR treatment inhibited the growth of retinoblastoma tumor in vivo via AMPK/mTORC1 pathway and by apoptogenic, anti-proliferative, anti-angiogenesis mechanism. AICAR is a promising novel non-chemotherapeutic drug that may be effective as an adjuvant in treating Retinoblastoma.

Enterococcus faecalis is a Gram-positive commensal member of the gut microbiota of a wide range of organisms. With the advent of antibiotic therapy, it has emerged as a multidrug resistant, hospital-acquired pathogen. Highly virulent strains of E. faecalis express a pore-forming exotoxin, called cytolysin, which lyses both bacterial and eukaryotic cells in response to quorum signals. Originally described in the 1930s, the cytolysin is a member of a large class of lanthionine-containing bacteriocins produced by Gram-positive bacteria. While the cytolysin shares some core features with other lantibiotics, it possesses unique characteristics as well. The current understanding of cytolysin biosynthesis, structure/function relationships, and contribution to the biology of E. faecalis are reviewed, and opportunities for using emerging technologies to advance this understanding are discussed.

PURPOSE: To compare accuracy of intraocular lens (IOL) power calculation formulae in infantile eyes with primary IOL implantation. DESIGN: Comparative case series. METHODS: The Hoffer Q, Holladay 1, Holladay 2, Sanders-Retzlaff-Kraff (SRK) II, and Sanders-Retzlaff-Kraff theoretic (SRK/T) formulae were used to calculate predicted postoperative refraction for eyes that received primary IOL implantation in the Infant Aphakia Treatment Study. The protocol targeted postoperative hyperopia of +6.0 or +8.0 diopters (D). Eyes were excluded for invalid biometry, lack of refractive data at the specified postoperative visit, diagnosis of glaucoma or suspected glaucoma, or sulcus IOL placement. Actual refraction 1 month after surgery was converted to spherical equivalent and prediction error (predicted refraction - actual refraction) was calculated. Baseline characteristics were analyzed for effect on prediction error for each formula. The main outcome measure was absolute prediction error. RESULTS: Forty-three eyes were studied; mean axial length was 18.1 ± 1.1 mm (in 23 eyes, it was <18.0 mm). Average age at surgery was 2.5 ± 1.5 months. Holladay 1 showed the lowest median absolute prediction error (1.2 D); a paired comparison of medians showed clinically similar results using the Holladay 1 and SRK/T formulae (median difference, 0.3 D). Comparison of the mean absolute prediction error showed the lowest values using the SRK/T formula (1.4 ± 1.1 D), followed by the Holladay 1 formula (1.7 ± 1.3 D). Calculations with an optimized constant showed the lowest values and no significant difference between the Holladay 1 and SRK/T formulae (median difference, 0.3 D). Eyes with globe AL of less than 18 mm had the largest mean and median prediction error and absolute prediction error, regardless of the formula used. CONCLUSIONS: The Holladay 1 and SRK/T formulae gave equally good results and had the best predictive value for infant eyes.

OBJECTIVE: To identify nutritional and weight gain limitations associated with retinopathy of prematurity (ROP) severity among very preterm newborns. PATIENTS AND METHODS: 1180 infants <28 weeks GA at birth with ROP examination results were grouped and analyzed by quartile of weekly total calorie, carbohydrate, protein, and lipid intake, as well as growth velocity between postnatal days 7 and 28 (adjusted for GA and birth weight Z-score). ROP was categorized by development of no, mild (

OBJECTIVE: Vascular endothelial cells (ECs) are continuously exposed to blood flow that contributes to the maintenance of vessel structure and function; however, the effect of hemodynamic forces on transforming growth factor-β (TGF-β) signaling in the endothelium is poorly described. We examined the potential role of TGF-β signaling in mediating the protective effects of shear stress on ECs. APPROACH AND RESULTS: Human umbilical vein ECs (HUVECs) exposed to shear stress were compared with cells grown under static conditions. Signaling through the TGF-β receptor ALK5 was inhibited with SB525334. Cells were examined for morphological changes and harvested for analysis by real-time polymerase chain reaction, Western blot analysis, apoptosis, proliferation, and immunocytochemistry. Shear stress resulted in ALK5-dependent alignment of HUVECs as well as attenuation of apoptosis and proliferation compared with static controls. Shear stress led to an ALK5-dependent increase in TGF-β3 and Krüppel-like factor 2, phosphorylation of endothelial NO synthase, and NO release. Addition of the NO donor S-nitroso-N-acetylpenicillamine rescued the cells from apoptosis attributable to ALK5 inhibition under shear stress. Knockdown of TGF-β3, but not TGF-β1, disrupted the HUVEC monolayer and prevented the induction of Krüppel-like factor 2 by shear. CONCLUSIONS: Shear stress of HUVECs induces TGF-β3 signaling and subsequent activation of Krüppel-like factor 2 and NO, and represents a novel role for TGF-β3 in the maintenance of HUVEC homeostasis in a hemodynamic environment.

PURPOSE: Ocular local anesthetics currently used in routine clinical practice for corneal anesthesia are short acting and their ability to delay corneal healing makes them unsuitable for long-term use. In this study, we examined the effect of the site 1 sodium channel blocker tetrodotoxin (TTX) on the duration of corneal anesthesia, applied with either proparacaine (PPC) or the chemical permeation enhancer octyl-trimethyl ammonium bromide (OTAB). The effect of test solutions on corneal healing was also studied. METHODS: Solutions of TTX, PPC, and OTAB, singly or in combination, were applied topically to the rat cornea. The blink response, an indirect measure of corneal sensitivity, was recorded using a Cochet-Bonnet esthesiometer, and the duration of corneal anesthesia was calculated. The effect of test compounds on the rate of corneal epithelialization was studied in vivo after corneal debridement. RESULTS: Combination of TTX and PPC resulted in corneal anesthesia that was 8 to 10 times longer in duration than that from either drug administered alone, whereas OTAB did not prolong anesthesia. The rate of corneal healing was moderately delayed after coadministration of TTX and PPC. CONCLUSIONS: Coadministration of TTX and PPC significantly prolonged corneal anesthesia, but in view of delayed corneal reepithelialization, caution is suggested in the use of the drug combination.

PURPOSE: Fuchs endothelial corneal dystrophy (FECD) is an oxidative stress disorder that leads to age-related and gradual loss of corneal endothelial cells resulting in corneal edema and loss of vision. To date, other than surgical intervention, there are no treatment options for patients with FECD. We have shown that in FECD, there is a deficiency in nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated antioxidant defense due to decreased Nrf2 nuclear translocation and activation of antioxidant response element (ARE). In this study, we used sulforaphane (SFN) and D3T to investigate a strategy of targeting Nrf2-ARE in FECD. METHODS: FECD and normal ex vivo corneas and human corneal endothelial cell lines were pretreated with SFN or D3T and exposed to oxidative stress with tert-Butyl hydroperoxide (tBHP). Apoptosis was detected with TUNEL. Cellular localization of Nrf2 and p53 was assessed by immunohistochemistry. Effect of SFN was determined by using DCFDA assay, Western blot and real-time PCR. RESULTS: After pretreatment with SFN, oxidative stress was induced with tBHP. In ex vivo FECD specimens, SFN decreased CEC apoptosis by 55% in unstressed group and by 43% in tBHP-treated specimens. SFN enhanced nuclear translocation of Nrf2 in FECD specimens and decreased p53 staining under oxidative stress. Pretreatment with SFN enhanced cell viability by decreasing intracellular reactive oxygen species production. Upregulation of Nrf2 levels led to increased synthesis of DJ-1, heme oxygenase 1, and nicotinamide adenine dinucleotide quinone oxidoreductase-1. SFN significantly upregulated major ARE-dependent antioxidants and ameliorated oxidative stress-induced apoptosis in FECD. CONCLUSIONS: Our results suggest that targeting Nrf2-ARE pathway may arrest degenerative cell loss seen in FECD.

The cellular entry of viruses represents a critical area of study, not only for viral tropism, but also because viral entry dictates the nature of the immune response elicited upon infection. Epidemic keratoconjunctivitis (EKC), caused by viruses within human adenovirus species D (HAdV-D), is a severe, ocular surface infection associated with corneal inflammation. Clathrin-mediated endocytosis has previously been shown to play a critical role in entry of other HAdV species into many host cell types. However, HAdV-D endocytosis into corneal cells has not been extensively studied. Herein, we show an essential role for cholesterol rich, lipid raft microdomains and caveolin-1, in the entry of HAdV-D37 into primary human corneal fibroblasts. Cholesterol depletion using methyl-β-cyclodextrin (MβCD) profoundly reduced viral infection. When replenished with soluble cholesterol, the effect of MβCD was reversed, allowing productive viral infection. HAdV-D37 DNA was identified in caveolin-1 rich endosomal fractions after infection. Src kinase activity was also increased in caveolin-1 rich endosomal fractions after infection, and Src phosphorylation and CXCL1 induction were both decreased in caveolin-1-/- mice corneas compared to wild type mice. siRNA knock down of caveolin-1 in corneal cells reduced chemokine induction upon viral infection, and caveolin-1-/- mouse corneas showed reduced cellular entry of HAdV-D37. As a control, HAdV-C2, a non-corneal pathogen, appeared to utilize the caveolar pathway for entry into A549 cells, but failed to infect corneal cells entirely, indicating virus and cell specific tropism. Immuno-electron microscopy confirmed the presence of caveolin-1 in HAdV-D37-containing vesicles during the earliest stages of viral entry. Collectively, these experiments indicate for the first time that HAdV-D37 uses a lipid raft mediated caveolin-1 associated pathway for entry into corneal cells, and connects the processes of viral entry with downstream proinflammatory cell signaling.

In children or young adults, the morphology of the skull can be altered by excessive drainage of CSF following placement of a ventriculoperitoneal (VP) shunt. In Sunken Eyes, Sagging Brain Syndrome, gradual enlargement of the orbital cavity occurs from low or negative intracranial pressure (ICP), leading to progressive bilateral enophthalmos. The authors report several heretofore unrecognized manifestations of this syndrome, which developed in a 29-year-old man with a history of VP shunt placement following a traumatic brain injury at the age of 9 years. Magnetic resonance imaging showed typical features of chronic intracranial hypotension, and lumbar puncture yielded an unrecordable subarachnoid opening pressure. The calvaria was twice its normal thickness, owing to contraction of the inner table. The paranasal sinuses were expanded, with aeration of the anterior clinoid processes, greater sphenoid wings, and temporal bones. The sella turcica showed a 50% reduction in cross-sectional area as compared with that in control subjects, resulting in partial extrusion of the pituitary gland. These new features broaden the spectrum of clinical findings associated with low ICP. Secondary installation of a valve to restore normal ICP is recommended to halt progression of these rare complications of VP shunt placement.

PURPOSE: The Cutler-Beard procedure is a commonly used technique to reconstruct large upper eyelid defects. Eyelid retraction and entropion are common complications. To prevent these problems, the authors modified the traditional Cutler-Beard procedure with secondary placement of an autologous tarsoconjunctival graft. METHODS: This is a retrospective review of 2 patients with large upper eyelid defects necessitating upper eyelid reconstruction. The initial stage is unaltered. At the time of flap division, a tarsoconjunctival graft from the contralateral upper eyelid is sutured to the posterior surface of the newly constructed upper eyelid. Two patients underwent this procedure, and follow up was 4 and 23 months, respectively. Patients developed no postoperative complications, including entropion or retraction. CONCLUSIONS: This modification to the Cutler-Beard operation is a technically simple procedure that can restore a more anatomically correct eyelid and can prevent subsequent entropion or retraction. This technique is unique, offering 3 major advances: first, placing the graft at the second surgical stage; second, replacing the tarsus and conjunctiva with like tissue; and third, preserving a lip of conjunctiva to cover the edge of the newly reconstructed upper eyelid.

PURPOSE: To report the features of the rare and under-recognized condition of canaliculops (or canaliculocele) of the eyelid, which is a dilation of the canaliculus, and to evaluate treatment with marsupialization. DESIGN: Retrospective interventional case series. METHODS: The records of 2 patients with canaliculops from the Massachusetts Eye and Ear Infirmary were reviewed. Data collected included clinical history, surgical technique, histopathologic analysis, and comparative immunohistochemical analysis of a range of cytokeratins in normal conjunctival epithelium, normal canalicular epithelium, and canaliculops epithelium. RESULTS: Two women, 53 and 66 years of age, experienced chronic, noninflammatory, painless medial eyelid and eyelid margin fluctuant swelling after earlier trauma or eyelid surgery. The external mass was accompanied by a whitish opalescent or bluish discoloration of a palpebral surface bulge. Biopsy revealed multilaminar (up to 12 cells thick), nonkeratinizing, tightly packed small squamous epithelial cells that surmounted a highly regimented basal layer with a picket fence arrangement. No goblet cells or subepithelial inflammation were present. Immunohistochemistry revealed only superficial CK7 immunostaining and positive patchy suprabasilar CK17 staining in the canaliculops epithelium, contrasting with their full-thickness positivity and negativity, respectively, in normal conjunctival epithelium. Marsupialization achieved resolution of the condition in each patient. CONCLUSIONS: An improved awareness of the normal canalicular epithelial structure and its immunohistochemical features can definitively separate canaliculops from conjunctival cysts. Previous treatment of canaliculops has involved complete excisions. Canaliculops may, however, be effectively treated with less invasive marsupialization while obtaining an adequate biopsy specimen for histopathologic diagnosis.

PURPOSE: To explore the visual and anatomic outcomes of patients with refractory or recurrent neovascular age-related macular degeneration (AMD) who were converted from bevacizumab and/or ranibizumab to aflibercept. DESIGN: Two-center, retrospective chart review. METHODS: Treatment history, visual acuity (VA), and central macular thickness (CMT) on spectral-domain optical coherence tomography were collected. Patients were divided into "refractory" (persistent exudation despite monthly injections) or "recurrent" (exudation suppressed, but requiring frequent injections). RESULTS: One hundred and two eyes of 94 patients were included; 68 were refractory and 34 were recurrent. Eyes received a mean of 20.4 prior bevacizumab/ranibizumab injections and a mean of 3.8 aflibercept injections. Mean follow-up was 18 weeks. Mean VA was 20/50-1 before conversion, 20/50-2 after 1 aflibercept injection (P = .723), and 20/50+2 after the final injection (P = .253). Subgroup analysis of refractory and recurrent cases also showed stable VA. Of the refractory cases, mean CMT had improved after 1 injection (P < .001) and the final injection (P < .001). Intraretinal (P < .001) and subretinal (P < .001) fluid decreased after 1 injection, and the mean injection interval was extended from 5.2 to 6.2 weeks (P = .003). Of the recurrent cases, mean CMT improved after 1 injection (P < .001) and the final injection (P < .001). Intraretinal (P = .003) and subretinal (P = .046) fluid decreased after 1 injection, and the mean injection interval was extended from 7.2 to 9.5 weeks (P = .001). CONCLUSIONS: Converting patients with chronic neovascular AMD to aflibercept results in stabilized vision and improved anatomic outcomes, while allowing injection intervals to be extended.

Sturge-Weber syndrome is a nonhereditary congenital neurocutaneous syndrome characterized by leptomeningeal angiomatosis, facial nevus flammeus, and diffuse choroidal hemangioma, which when complicated by total retinal detachment, portend a poor prognosis. Management is often limited to salvage external beam irradiation. We present a modified proton therapy technique for young children with total bullous retinal detachments that uses standard fractionation low-dose proton radiotherapy to decrease the risk of radiation complications. Treatment techniques for young children who cannot cooperate with conventional radiation protocols are also described.

Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a paraneoplastic syndrome characterized by cataract, photoreceptor loss and subretinal fluid overlying patchy areas of retinal pigment epithelium atrophy, and a diffusely thickened choroid with focal nodules. We present the case of a 64-year-old woman with a history of endometrial adenocarcinoma who developed BDUMP with bilateral exudative retinal detachments with inferior peripheral retinal ischemia. This new finding of peripheral nonperfusion expands the spectrum of BDUMP.

To study bilateral nerve changes in a newly developed novel mouse model for neurotrophic keratopathy by approaching the trigeminal nerve from the lateral fornix. Surgical axotomy of the ciliary nerve of the trigeminal nerve was performed in adult BALB/c mice at the posterior sclera. Axotomized, contralateral, and sham-treated corneas were excised on post-operative days 1, 3, 5, 7 and 14 and immunofluorescence histochemistry was performed with anti-β-tubulin antibody to evaluate corneal nerve density. Blink reflex was evaluated using a nylon thread. The survival rate was 100% with minimal bleeding during axotomy and a surgical time of 8±0.5 minutes. The blink reflex was diminished at day 1 after axotomy, but remained intact in the contralateral eyes in all mice. The central and peripheral subbasal nerves were not detectable in the axotomized cornea at day 1 (p<0.001), compared to normal eyes (101.3±14.8 and 69.7±12.0 mm/mm² centrally and peripherally). Interestingly, the subbasal nerve density in the contralateral non-surgical eyes also decreased significantly to 62.4±2.8 mm/mm² in the center from day 1 (p<0.001), but did not change in the periphery (77.3±11.7 mm/mm², P = 0.819). Our novel trigeminal axotomy mouse model is highly effective, less invasive, rapid, and has a high survival rate, demonstrating immediate loss of subbasal nerves in axotomized eyes and decreased subbasal nerves in contralateral eyes after unilateral axotomy. This model will allow investigating the effects of corneal nerve damage and serves as a new model for neurotrophic keratopathy.

PURPOSE: To describe a cohort of children with late-recognized primary congenital glaucoma (LRPCG), including age of presentation, age-related diagnostic signs, clinical abnormalities, and results of glaucoma surgery. METHODS: The medical records of 31 patients (49 eyes) with PCG recognized after 1 year of age were reviewed retrospectively. Patients were confirmed to have PCG based on their increased intraocular pressure (IOP), anterior segment abnormalities including findings on gonioscopy, and the absence of other causes of childhood glaucoma. The outcome of glaucoma surgery was reviewed and success measured by assessment of the relative control of IOP, occurrence of significant complications, and need for additional glaucoma surgery. RESULTS: Average age at diagnosis of glaucoma was 4.7 years (36% diagnosed at > 4 years of age). The most common initial diagnostic signs were corneal enlargement (46%, average age of 2.0 years), photophobia (20%, average age of 3.3 years), and suspected poor visual acuity (32%, average age of 9.9 years). Corneal cloudiness was not an initial sign for any patient. Haab's striae were present in 60% of the affected 49 eyes. Gonioscopy findings were abnormal in 82%, but the ciliary body band was seen in 81% and the scleral spur was visible in 47%. Sixty-one goniotomy procedures were performed for 39 eyes with overall success in 95% (37 eyes) and complete success in 65% (27 eyes). The final visual acuity was 20/200 or worse in 31% (15 eyes) and 20/40 or better in 60% (29 eyes). CONCLUSIONS: An awareness of and familiarity with the subtle diagnostic signs of LRPCG can enable its differentiation from primary juvenile glaucoma and contribute to earlier recognition and treatment. Glaucoma surgery is often required for LRPCG and goniosurgery is the recommended initial procedure.

Uveal melanoma (UM) has a strong propensity to metastasize and the prognosis for metastatic disease is very poor. It has been suggested that occult micrometastases are already present, but undetectable, in many patients at the time when the primary ocular tumor is diagnosed and treated. To identify high-risk patients for close monitoring and early intervention with prophylactic adjuvant systemic therapy, an accurate predictive system is necessary for stratifying those patients at risk of developing metastatic disease. To date, many clinical and histopathological features, molecular pathway characteristics, and genetic fingerprints of UM have been suggested for disease prognostication. Among the newest of them, tumor genetics has received the most attention in demonstrating promise as a prognostic tool. Because of the plethora of recent developments, we summarize and compare in this review the important standard and more advanced cytogenetic prognostic markers. We further describe the variety of genetic tests available for prognostication of UM, and provide a critical assessment of the respective advantages and disadvantages of these tools.

Primary open-angle glaucoma (POAG) is a common disease with complex inheritance. The identification of genes predisposing to POAG is an important step toward the development of novel gene-based methods of diagnosis and treatment. Genome-wide association studies (GWAS) have successfully identified genes contributing to complex traits such as POAG however, such studies frequently require very large sample sizes, and thus, collaborations and consortia have been of critical importance for the GWAS approach. In this report we describe the formation of the NEIGHBOR consortium, the harmonized case control definitions used for a POAG GWAS, the clinical features of the cases and controls, and the rationale for the GWAS study design.

Epithelial cells lining mucosal surfaces impose multiple barriers to viral infection. At the ocular surface, the carbohydrate-binding protein galectin-3 maintains barrier function by cross-linking transmembrane mucins on the apical glycocalyx. Despite these defense mechanisms, many viruses have evolved to exploit fundamental cellular processes on host cells. Here, we use affinity assays to show that herpes simplex virus type 1 (HSV-1), but not HSV-2, binds human galectin-3. Knockdown of galectin-3 in human corneal keratinocytes by small interfering RNA significantly impaired HSV-1 infection, but not expression of nectin-1, indicating that galectin-3 is a herpesvirus entry mediator. Interestingly, exposure of epithelial cell cultures to transmembrane mucin isolates decreased viral infectivity. Moreover, HSV-1 failed to elute the biological counterreceptor MUC16 from galectin-3 affinity columns, suggesting that association of transmembrane mucins to galectin-3 provides protection against viral infection. Together, these results indicate that HSV-1 exploits galectin-3 to enhance virus attachment to host cells and support a protective role for transmembrane mucins under physiological conditions by masking viral entry mediators on the epithelial glycocalyx.