The functional competence of corneal endothelial cells (CEnCs) is critical for survival of corneal allografts, but these cells are often targets of the immune response mediated by graft-attacking effector T cells. Although regulatory T cells (Tregs) have been studied for their role in regulating the host's alloimmune response towards the graft, the cytoprotective function of these cells on CEnCs has not been investigated. The aim of this study was to determine whether Tregs suppress effector T cell-mediated and inflammatory cytokine-induced CEnC death, and to elucidate the mechanism by which this cytoprotection occurs. Using 2 well-established models of corneal transplantation (low-risk and high-risk models), we show that Tregs derived from low-risk graft recipients have a superior capacity in protecting CEnCs against effector T cell-mediated and interferon-γ and tumor necrosis factor-α-induced cell death compared to Tregs derived from high-risk hosts. We further demonstrate that the cytoprotective function of Tregs derived from low-risk hosts occurs independently of direct cell-cell contact and is mediated by the immunoregulatory cytokine IL-10. Our study is the first to report that Tregs provide cytoprotection for CEnCs through secretion of IL-10, indicating potentially novel therapeutic targets for enhancing CEnC survival following corneal transplantation.

PURPOSE: To review the published literature assessing the efficacy of binocular therapy for the treatment of amblyopia compared with standard treatments. METHODS: Literature searches with no date restrictions and limited to the English language were conducted in January 2018 and updated in April 2019 in the PubMed database and the Cochrane Library database with no restrictions. The search yielded 286 citations, and the full text of 50 articles was reviewed. Twenty articles met the inclusion criteria for this assessment and were assigned a level of evidence rating by the panel methodologist. Six studies were rated level I, 1 study was rated level II, and 13 studies were rated level III because of the impact on the development and popularization of this technology. RESULTS: Two of the level I and II studies reviewed described a significant improvement in visual acuity in the binocular group versus standard patching standard treatment (the total number of patients in these 2 studies was 147). However, the 5 studies that failed to show a visual improvement from binocular therapy compared with standard treatments were larger and more rigorously designed (the total number of patients in these 5 studies was 813). Level I and II studies also failed to show a significant improvement over baseline in sensory status, including depth of suppression and stereopsis of those treated with binocular therapy. Several smaller level III case series (total number of patients in these 13 studies was 163) revealed more promising results than the binocular treatments studied in the level I and II studies, especially using treatments that are more engaging and are associated with better compliance. CONCLUSIONS: There is no level I evidence to support the use of binocular treatment as a substitute for current therapies for amblyopia (including patching and optical treatment). Furthermore, 2 large randomized controlled trials showed inferior performance compared with standard patching treatment. On the basis of this review of the published literature, binocular therapy cannot be recommended as a replacement for standard amblyopia therapy. However, more research is needed to determine the potential benefits of proposed binocular treatments in the future.

Over the last decade, genetic studies, including genome-wide association studies (GWAS), have accelerated the discovery of genes and genomic regions contributing to primary open-angle glaucoma (POAG), a leading cause of irreversible vision loss. Here, we review the findings of genetic studies of POAG published in English prior to September 2019. In total, 74 genomic regions have been associated at a genome-wide level of significance with POAG susceptibility. Recent POAG GWAS provide not only insight into global and ethnic-specific genetic risk factors for POAG susceptibility across populations of diverse ancestry, but also important functional insights underlying biological mechanisms of glaucoma pathogenesis. In this review, we also summarize the genetic overlap between POAG, glaucoma endophenotypes, such as intraocular pressure and vertical cup-disc ratio (VCDR), and other eye disorders. We also discuss approaches recently developed to increase power for POAG locus discovery and to predict POAG risk. Finally, we discuss the recent development of POAG gene-based therapies and future strategies to treat glaucoma effectively. Understanding the genetic architecture of POAG is essential for an earlier diagnosis of this common eye disorder, predictive testing of at-risk patients, and design of gene-based targeted medical therapies none of which are currently available.

Cannabis is the most prevalent drug in the world and its consumption is growing. Cannabinoid receptors are present in the human central nervous system. Recent studies show evidence of the effects of cannabinoids on the retina, and synthesising the results of these studies may be relevant for ophthalmologists. Thus, this review adopts standardised, systematic review methodology to investigate the effects of exposure to cannabis and components on the retina. We searched five online databases for the combined terms for outcome ("retina") and exposure ("cannabis"). Eligibility of studies were conducted by two independent reviewers, and risk of bias was assessed. We retrieved 495 studies, screened 229 studies, assessed 52 studies for eligibility, and included 16 studies for qualitative analysis. The cannabinoids most frequently investigated were delta-9-tetrahydrocannabinol (THC), abnormal cannabidiol, synthetic cannabinoid, and cannabidiol (CDB). The outcomes most studied were neuroretinal dysfunction, followed by vascular effects. The studies also included investigation of neuroprotective and anti-inflammatory effects and teratogenic effects. This review suggests that cannabinoids may have an important role in retinal processing and function.

PURPOSE: Orbital trauma, particularly with open globe injury, can have a wide range of visual outcomes, which can be difficult to predict at presentation. Clinical features on presentation may provide insight into visual prognosis. We hypothesized that patients with open globe injuries and concomitant orbital fractures have poorer visual outcomes than patients without orbital fractures. METHODS: We reviewed the charts of 77 patients with isolated open globe injuries (OG) and 76 patients with open globe injuries and concomitant orbital fractures (OGOF). Multivariate regression analysis was performed to assess the relative influence of individual presenting historical and clinical features on visual outcome. RESULTS: OGOF patients were more likely to have sustained blunt trauma than a sharp, penetrating injury compared to OG patients. Ocular wound locations were more posterior and likely to involve multiple zones in OGOF compared to OG patients. Among OGOF patients, orbital floor fractures were the most common and roof fractures were the least common, but the latter was associated with presenting NLP vision and multiple zone involvement. The presence of an orbital fracture independently increased the odds of subsequent evisceration/enucleation (OR: 4.6, 95% CI 1.3-20.1, = .0246) and NLP vision (OR: 6.81, 95% CI 2.42-21.85, = .0005) when controlling for zone, mechanism of injury, uveal prolapse and demographic variables. CONCLUSIONS: The presence of an orbital fracture independently confers a worse visual and ocular prognosis in patients with open globe injuries. Patients with open globe injuries in this category should be appropriately counseled.

BACKGROUND/AIMS: Although being a more objective tool for assessment and follow-up of angle closure, reliability studies have reported a moderate diagnostic performance for anterior segment optical coherence tomography (OCT) technologies when comparing with gonioscopy as the reference standard. We aim to determine factors associated with diagnostic disagreement in angle closure when assessed by anterior segment swept source OCT (SS-OCT, CASIA SS-1000; Tomey, Nagoya, Japan) and gonioscopy. METHODS: Cross-sectional study. A total of 2027 phakic subjects aged ≥50 years, with no relevant previous ophthalmic history, were consecutively recruited from a community polyclinic in Singapore. Gonioscopy and SS-OCT (128 radial scans) for the entire circumference of the angle were performed for each subject. A two-quadrant closed gonioscopic definition was used. On SS-OCT images, angle closure was defined as iridotrabecular contact (ITC) to the extent of ≥35%, ≥50% and ≥75% of the circumferential angle. Diagnostic disagreements between both methods, that is, false positives or overcalls and false negatives or undercalls were defined, respectively, as gonioscopic open/closed angles inversely assessed as closed/open by SS-OCT. RESULTS: Two hundred and seventy-two (14.7%) resulted in overcall results (false positives) when ≥50% of the angle circumference was closed using SS-OCT. These eyes had significantly wider (anterior chamber width, 11.7 vs 11.6 mm, p<0.001) and deeper (anterior chamber depth (ACD), 2.4 vs 2.2 mm, p<0.001) anterior chambers than eyes assessed by both methods as closed (true positives). Deeper ACD (OR 9.31) and lower lens vault (LV) (OR 0.04) were significantly associated with a false positive diagnosis in the multivariate analysis. Most of these cases had short (52.6%) or irregular (39%) ITC in SS-OCT images. CONCLUSIONS: We found that anterior chamber dimensions, determined by ACD and LV, were factors significantly associated with diagnostic disagreement between anterior segment SS-OCT and gonioscopy in angle closure assessment.

PURPOSE: Lubricin, a boundary lubricant, is the body's unique antiadhesive, antifibrotic, antifriction, and antiinflammatory glycoprotein. This amphiphile is produced by numerous tissues and acts to regulate a number of processes, such as homeostasis, shear stress, tissue development, innate immunity, inflammation, and wound healing. We hypothesize that lubricin is also synthesized and expressed by the amniotic membrane (AM), which also possesses antiadhesive, antifibrotic, and antiinflammatory properties. We also hypothesize that lubricin, at least in part, mediates these AM capabilities. Our goal was to test our hypothesis. METHODS: We obtained multiple samples of fresh, cryopreserved (CP), and freeze-dried (FD) human AMs, as well as fresh placental tissue as positive controls, and processed them for light microscopy, immunofluorescence, and western blot analyses. We also evaluated the ability of recombinant human lubricin to associate with FD-AMs. RESULTS: Our results demonstrate that all fresh placental, fresh AM, and CP-AM samples contained lubricin. Lubricin was expressed in placental chorionic villi, AM epithelial and stromal cells, and CP-AM epithelia. No lubricin could be detected in FD-AMs but could be restored in FD-AMs after overnight incubation with recombinant human lubricin. CONCLUSIONS: This study supports our hypothesis that lubricin is expressed in human AMs. In addition, our data show that preservation methods influence the extent of this expression. Indeed, the disappearance of lubricin in FD-AMs may explain why dried AM reportedly loses its antiinflammatory and antiscarring abilities. It is possible that lubricin may mediate, at least in part, many of the biological properties of AMs.