The emergence of diabetes as a global epidemic is accompanied by the rise in diabetes‑related retinal complications. Diabetic retinopathy, if left undetected and untreated, can lead to severe visual impairment and affect an individual's productivity and quality of life. Globally, diabetic retinopathy remains one of the leading causes of visual loss in the working‑age population. Teleophthalmology for diabetic retinopathy is an innovative means of retinal evaluation that allows identification of eyes at risk for visual loss, thereby preserving vision and decreasing the overall burden to the health care system. Numerous studies worldwide have found teleophthalmology to be a reliable and cost‑efficient alternative to traditional clinical examinations. It has reduced barriers to access to specialized eye care in both rural and urban communities. In teleophthalmology applications for diabetic retinopathy, it is critical that standardized protocols in image acquisition and evaluation are used to ensure low image ungradable rates and maintain the quality of images taken. Innovative imaging technology such as ultrawide field imaging has the potential to provide significant benefit with integration into teleophthalmology programs. Teleophthalmology programs for diabetic retinopathy rely on a comprehensive and multidisciplinary approach with partnerships across specialties and health care professionals to attain wider acceptability and allow evidence‑based eye care to reach a much broader population.

Central corneal thickness (CCT) is one of the most heritable ocular traits and it is also a phenotypic risk factor for primary open angle glaucoma (POAG). The present study uses the BXD Recombinant Inbred (RI) strains to identify novel quantitative trait loci (QTLs) modulating CCT in the mouse with the potential of identifying a molecular link between CCT and risk of developing POAG. The BXD RI strain set was used to define mammalian genomic loci modulating CCT, with a total of 818 corneas measured from 61 BXD RI strains (between 60-100 days of age). The mice were anesthetized and the eyes were positioned in front of the lens of the Phoenix Micron IV Image-Guided OCT system or the Bioptigen OCT system. CCT data for each strain was averaged and used to QTLs modulating this phenotype using the bioinformatics tools on GeneNetwork (www.genenetwork.org). The candidate genes and genomic loci identified in the mouse were then directly compared with the summary data from a human POAG genome wide association study (NEIGHBORHOOD) to determine if any genomic elements modulating mouse CCT are also risk factors for POAG.This analysis revealed one significant QTL on Chr 13 and a suggestive QTL on Chr 7. The significant locus on Chr 13 (13 to 19 Mb) was examined further to define candidate genes modulating this eye phenotype. For the Chr 13 QTL in the mouse, only one gene in the region (Pou6f2) contained nonsynonymous SNPs. Of these five nonsynonymous SNPs in Pou6f2, two resulted in changes in the amino acid proline which could result in altered secondary structure affecting protein function. The 7 Mb region under the mouse Chr 13 peak distributes over 2 chromosomes in the human: Chr 1 and Chr 7. These genomic loci were examined in the NEIGHBORHOOD database to determine if they are potential risk factors for human glaucoma identified using meta-data from human GWAS. The top 50 hits all resided within one gene (POU6F2), with the highest significance level of p = 10-6 for SNP rs76319873. POU6F2 is found in retinal ganglion cells and in corneal limbal stem cells. To test the effect of POU6F2 on CCT we examined the corneas of a Pou6f2-null mice and the corneas were thinner than those of wild-type littermates. In addition, these POU6F2 RGCs die early in the DBA/2J model of glaucoma than most RGCs. Using a mouse genetic reference panel, we identified a transcription factor, Pou6f2, that modulates CCT in the mouse. POU6F2 is also found in a subset of retinal ganglion cells and these RGCs are sensitive to injury.

Natural products have served as an inspiration to scientists both for their complex three-dimensional architecture and exquisite biological activity. Promysalin is one such Pseudomonad secondary metabolite that exhibits narrow-spectrum antibacterial activity, originally isolated from the rhizosphere. We herein utilize affinity-based protein profiling (AfBPP) to identify succinate dehydrogenase (Sdh) as the biological target of the natural product. The target was further validated in silico, in vitro, in vivo, and through the selection, and sequencing, of a resistant mutant. Succinate dehydrogenase plays an essential role in primary metabolism of Pseudomonas aeruginosa as the only enzyme that is involved both in the tricarboxylic acid cycle (TCA) and in respiration via the electron transport chain. These findings add credence to other studies that suggest that the TCA cycle is an understudied target in the development of novel therapeutics to combat P. aeruginosa, a significant pathogen in clinical settings.

PURPOSE: To determine the demographic features of patients affected by limbal stem cell deficiency (LSCD), and to identify the underlying causes of LSCD DESIGN: Retrospective, multi-center case series SETTING: Two large tertiary care ophthalmology hospitals SUBJECTS: Patients with a diagnosis of LSCD presenting from January 1, 2005 to December 31, 2014 METHODS: Records of patients with a clinical diagnosis of LSCD were reviewed. Demographic details and clinical features at presentation, as well as the underlying cause of LSCD (if identified) were noted. Descriptive statistical analysis and chart preparation were done. MAIN OUTCOME MEASURES: Type of LSCD (unilateral or bilateral), age and sex of patients, extent of LSCD (clock hours of limbus involved) and underlying cause of LSCD RESULTS: We found 1331 patients with LSCD in the ten year period under study. Unilateral LSCD was more common (791 patients) than bilateral LSCD (540 patients). Out of 1331 patients, 875 (65.74%) were male. The median age of patients was 24 years. Extent of LSCD could be determined in 1849 eyes, of which 1239 eyes (67%) had total LSCD. The underlying cause of LSCD could be identified in 1512 eyes. In cases of unilateral LSCD, ocular surface burns was the commonest identifiable cause ( 83.73%). The leading identifiable causes of bilateral LSCD were ocular surface burns (29.95%), allergic conjunctivitis (29.48%), Stevens Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) (23.11%), aniridia (9.43%) and mucous membrane pemphigoid (3.54%). Lime ("chuna") injury was responsible for ocular surface burns in 352 (62.08%) out of 567 cases in which the agent was identified. CONCLUSIONS: In our study, unilateral LSCD was more common than bilateral LSCD. Young males were commonly affected, with a majority of eyes suffering from total LSCD. Overall, ocular surface burns are the leading cause of LSCD.Unilateral and bilateral LSCD had a markedly different distribution of causes, necessitating different approaches to management.

PURPOSE: To present 2 patients in whom orbital radiation preceded the development of periorbital extranodal marginal zone lymphoma by more than a decade and to investigate the likelihood of this representing irradiation-induced malignancy. METHODS: Retrospective chart review and histopathologic study with immunohistochemistry of 2 cases. RESULTS: The first patient was a 58-year-old woman who developed an orbital mass within the vicinity of the lateral rectus muscle 17 years after external beam proton radiation therapy for an inferotemporal choroidal melanoma. The second patient was a 32-year-old woman who developed a mass in the right lacrimal gland 12 years after external beam photon radiation therapy for chronic inflammatory dacryoadenitis. Histopathologic and immunohistochemical studies confirmed orbital extranodal marginal zone lymphoma in both cases. Retrospective review of older histopathologic slides from the second patient revealed underlying immunoglobulin G4-related disease. DISCUSSION: The unusual sequence of events in these 2 cases raises the question of whether orbital radiation may in rare instances promote the development of orbital extranodal marginal zone lymphoma. The literature pertaining to irradiation-induced secondary malignancy in the orbit is reviewed. CONCLUSIONS: Clinicians should consider the possibility of a secondary malignancy when evaluating a patient with an orbital mass and a history of prior local radiation exposure.

Interleukin-1β (IL-1β) is a potent mediator of innate immunity commonly up-regulated in a broad spectrum of inflammatory diseases. When bound to its cell surface receptor, IL-1β initiates a signalling cascade that cooperatively induces the expression of canonical IL-1 target genes such as IL-8 and IL-6. Here, we present galectin-3 as a novel regulator of IL-1β responses in corneal keratinocytes. Using the SNAP-tag system and digitonin semi-permeabilization, we show that recombinant exogenous galectin-3 binds to the plasma membrane of keratinocytes and is internalized into cytoplasmic compartments. We find that exogenous galectin-3, but not a dominant negative inhibitor of galectin-3 polymerization lacking the N-terminal domain, exacerbates the response to IL-1β by stimulating the secretion of inflammatory cytokines. The activity of galectin-3 could be reduced by a novel d-galactopyranoside derivative targeting the conserved galactoside-binding site of galectins and did not involve interaction with IL-1 receptor 1 or the induction of endogenous IL-1β. Consistent with these observations, we demonstrate that small interfering RNA-mediated suppression of endogenous galectin-3 expression is sufficient to impair the IL-1β-induced secretion of IL-8 and IL-6 in a p38 mitogen-activated protein kinase-independent manner. Collectively, our findings provide a novel role for galectin-3 as an amplifier of IL-1β responses during epithelial inflammation through an as yet unidentified mechanism.

We evaluated the influence of an antioxidant and zinc nutritional supplement [the Age-Related Eye Disease Study (AREDS) formulation] on delaying or preventing progression to neovascular AMD (NV) in persons with age-related macular degeneration (AMD). AREDS subjects (n = 802) with category 3 or 4 AMD at baseline who had been treated with placebo or the AREDS formulation were evaluated for differences in the risk of progression to NV as a function of complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genotype groups. We used published genetic grouping: a two-SNP haplotype risk-calling algorithm to assess CFH, and either the single SNP rs10490924 or 372_815del443ins54 to mark ARMS2 risk. Progression risk was determined using the Cox proportional hazard model. Genetics-treatment interaction on NV risk was assessed using a multiiterative bootstrap validation analysis. We identified strong interaction of genetics with AREDS formulation treatment on the development of NV. Individuals with high CFH and no ARMS2 risk alleles and taking the AREDS formulation had increased progression to NV compared with placebo. Those with low CFH risk and high ARMS2 risk had decreased progression risk. Analysis of CFH and ARMS2 genotype groups from a validation dataset reinforces this conclusion. Bootstrapping analysis confirms the presence of a genetics-treatment interaction and suggests that individual treatment response to the AREDS formulation is largely determined by genetics. The AREDS formulation modifies the risk of progression to NV based on individual genetics. Its use should be based on patient-specific genotype.

The purpose of this study was to describe the histopathologic appearance of dermal eyelid fillers that were unexpectedly encountered in ophthalmic plastic surgery samples from patients with mild eyelid disfigurements, and to review eyelid cases with complications that had previously been described in the literature. A retrospective histopathologic study with Alcian blue, elastic, and Masson trichrome stains of 2 cases that were submitted to the Ocular Pathology Department was conducted, and a critical review of previously published cases of the histopathologic characteristics of dermal filler material in the periocular region was also conducted. Two periocular tissue samples were found to contain dermal filler material. In one case, porcine collagen appeared as amorphous or indistinctly microfibrillar aggregates that stained light blue with the Masson trichrome method. In the other case, hyaluronic acid gel appeared as vivid blue amorphous pools of material in extracellular locules after staining with the Alcian blue method. An inflammatory response was not observed in either case. Patients who undergo facial filler procedures may, at a later time, require a surgical excisional procedure from which a specimen is generated. Previously injected dermal filler that the patient neglected to mention may be present in the pathologic sample, potentially perplexing the unsuspecting pathologist. Both ophthalmic plastic surgeons and ocular pathologists should be aware of the histopathologic features of dermal fillers. It is helpful if a surgeon who submits a specimen to the pathology service makes note of any known prior use of facial filler material or is alert to its possible presence when unfamiliar foreign material is discovered in the dermis of the eyelids.

Local corticosteroid injections are frequently employed by ophthalmologists to treat a variety of ocular, periocular, and orbital inflammatory conditions. Triamcinolone acetonide is a slowly dissolving crystalline corticosteroid that is often used for this purpose because of its prolonged anti-inflammatory effect. On occasion, previously injected corticosteroid material persists in tissues longer than anticipated, creating nodules that may masquerade as other disease conditions, or appearing incidentally in excised lesions on histopathologic examination. The histopathologic features of corticosteroid residues are unfamiliar to most ophthalmic pathologists and general pathologists. These features are described herein. Triamcinolone acetonide deposits in the skin appear as pale eosinophilic lakes of acellular frothy material on hematoxylin-eosin staining and are occasionally surrounded by a mild inflammatory reaction.

PURPOSE: To delineate the histopathologic appearance of gelatin-based hemostatic agents, Surgiflo, Gelfoam, and Floseal, which are used by ophthalmic plastic surgeons, and which may incidentally be found as foreign materials in histopathologic tissue samples. METHODS: Histopathologic analysis was performed with hematoxylin-eosin, periodic acid-Schiff, Masson trichrome, and elastin staining on tissue samples in which gelatin-based agents were found. To better characterize these materials, similar analyses were performed on in vitro samples of commonly used gelatin-based hemostatic agents. RESULTS: Surgiflo and Gelfoam are composed of small stellate pieces of gelatin with a smooth, homogeneous quality. In tissues, they are faintly positive with periodic acid-Schiff staining, amphophilic with Masson trichrome staining, and ink-black with elastin staining. Floseal has a distinctly different morphology of large rectangular sheets, yet almost identical in vitro staining properties. DISCUSSION: While the morphology of the gelatin-based hemostatic agents is consistent under various conditions, the staining properties of these materials differ based on whether they have been in contact with human tissue. CONCLUSIONS: Gelatin-derived hemostatic agents are best identified based on their morphologic characteristics. Elastin staining highlights these materials prominently within tissue samples and may be helpful in distinguishing them from other foreign materials.