AIMS: To evaluate ocular disease characteristics and successful therapeutic regimens in patients with scleritis associated with relapsing polychondritis (RP). To compare these features with those seen in patients with scleritis associated with other systemic immune-mediated diseases (SIMD). METHODS: Electronic health records of 13 scleritis patients associated with RP were analysed and compared with those of 113 scleritis patients associated with other SIMD seen at two tertiary referral centres. RESULTS: Scleritis in patients with RP was often bilateral (92.3%), diffuse (76.9%), recurrent (84.6%), sometimes with decreased vision (46.2%), anterior uveitis (38.5%), peripheral keratitis (15.4%) and ocular hypertension (30.8%). Patients with scleritis associated with RP more often had bilateral scleritis (p=0.001), necrotising scleritis (23.1%; p=0.02), recurrences (p=0.001) and decreased vision (three of the six with legal blindness; p=0.012), as compared with patients who had scleritis associated with other SIMD. Nine patients (69.2%) had one or more SIMD other than RP, including systemic vasculitis (4) or other autoimmune disease (8); they antedated RP by 9 years (range 2-21 years). Successful therapy included cyclophosphamide (5), methotrexate (3), azathioprine (3), mycophenolate mofetil (2), infliximab (2) and adalimumab (1). CONCLUSIONS: Scleritis may be the first manifestation whose study leads to the diagnosis of RP. Scleritis associated with RP is more often bilateral, necrotising, recurrent and associated with decrease of vision than scleritis associated with other SIMD. About 69.2% of patients will have an additional SIMD disorder. Scleritis associated with RP most often will require immunomodulatory therapy. Occasionally, scleritis with RP may appear while using antitumor necrosis factor α agents.

Copy number variability at 16p13.11 has been associated with intellectual disability, autism, schizophrenia, epilepsy, and attention-deficit hyperactivity disorder. Adolescent/adult- onset psychosis has been reported in a subset of these cases. Here, we report on two children with CNVs in 16p13.11 that developed psychosis before the age of 7. The genotype and neuropsychiatric abnormalities of these patients highlight several overlapping genes that have possible mechanistic relevance to pathways previously implicated in Autism Spectrum Disorders, including the mTOR signaling and the ubiquitin-proteasome cascades. A careful screening of the 16p13.11 region is warranted in patients with childhood onset psychosis. © 2016 Wiley Periodicals, Inc.

A 12-month-old male infant, noted from birth to have a diffuse right temporal epibulbar thickening that encroached on the limbus inferotemporally, was found to manifest stigmata of Goldenhar syndrome, including a limbal dermoid with vellus hairs, esotropia, astigmatism, fullness and ectropion of the lower eyelid, preauricular skin tag, agenesis of the right kidney, and a supernumerary rib. In the excised epibulbar specimen, in addition to a solid dermoid, lobules of lacrimal gland tissue were interpreted as a portion of the palpebral or orbital lobes. This tissue displayed a unique histopathologic finding. Within some of the lobules were cuffs of eosinophilic squamous (epidermoid) cells that surrounded the intralobular ductules and made variable incursions into, with replacement of, the acinar units. Immunohistochemistry disclosed that the normal acinar and lumen-forming ductular cells were intermediate weight cytokeratin7-positive. The acinar cells were additionally gross cystic disease fluid protein-15 positive. The cells of the squamous cuffs were heavy weight cytokeratin 5/6-positive. The outermost basal cells of the cuffs were cytokeratin 14-positive, in common with the myoepithelial cells of the acini. The intraacinar squamous cells were negative for smooth muscle actin and gross cystic disease fluid protein-15. These findings suggest, but do not prove, that the source of the periductular and acinar squamous metaplasia was the germinal transitional cells where the acinar myoepithelium interfaces and imperceptibly converts into ductular basal cells. The foregoing findings are evaluated in the context of the panoply of ocular, facial, and visceral anomalies manifested in Goldenhar spectrum.

A genomic region located on chromosome 9p21 is associated with primary open-angle glaucoma and normal tension glaucoma in genome-wide association studies. The genomic region contains the gene for a long noncoding RNA called CDKN2B-AS, two genes that code for cyclin-dependent kinase inhibitors 2A and 2B (CDKN2A/p16(INK4A) and CDKN2B/p15(INK4B)) and an additional protein (p14(ARF)). We used a transgenic mouse model in which 70 kb of murine chromosome 4, syntenic to human chromosome 9p21, are deleted to study whether this deletion leads to a discernible phenotype in ocular structures implicated in glaucoma. Homozygous mice of this strain were previously reported to show persistent hyperplastic primary vitreous. Fundus photography and optical coherence tomography confirmed that finding but showed no abnormalities for heterozygous mice. Optokinetic response, eletroretinogram, and histology indicated that the heterozygous and mutant retinas were normal functionally and morphologically, whereas glial cells were activated in the retina and optic nerve head of mutant eyes. In quantitative PCR, CDKN2B expression was reduced by approximately 50% in the heterozygous mice and by 90% in the homozygous mice, which suggested that the CDKN2B knock down had no deleterious consequences for the retina under normal conditions. However, compared with wild-type and heterozygous animals, the homozygous mice are more vulnerable to retinal ganglion cell loss in response to elevated intraocular pressure.

PURPOSE: To investigate associations between serum 25-hydroxyvitamin D levels and dry eye syndrome (DES), and to evaluate the differential effect of vitamin D on ocular diseases including age-related macular disease (AMD), diabetic retinopathy (DR), cataract, and DES. METHODS: A total of 16,396 participants aged >19 years were randomly selected from the Korean National Health and Nutrition Examination Survey. All participants participated in standardized interviews, blood 25-hydroxyvitamin D level evaluations, and comprehensive ophthalmic examinations. DES was defined by a history of clinical diagnosis of dry eyes by a physician. The association between vitamin D and DES was compared to the associations between vitamin D and AMD, DR, cataract, and DES from our previous studies. RESULTS: The odds of DES non-significantly decreased as the quintiles of serum 25-hydroxyvitamin D levels increased (quintile 5 versus 1, OR = 0.85, 95%CI: 0.55-1.30, P for trend = 0.076) after adjusting for potential confounders including age, sex, hypertension, diabetes, smoking status, and sunlight exposure times. The relative odds of DES (OR = 0.70, 95% CI: 0.30-1.64) and cataract (OR = 0.76, 95% CI: 0.59-0.99) were relatively high, while those of DR (OR = 0.37, 95% CI: 0.18-0.76) and late AMD (OR = 0.32, 95% CI: 0.12-0.81) were lower in men. CONCLUSIONS: The present study does not support an association between serum 25-hydroxyvitamin D levels and DES. The preventive effect of serum 25-hydroxyvitamin D may be more effective for DR and late AMD than it is for cataract and DES.

PURPOSE: To evaluate the anatomical outcomes of corneal patch grafts in patients with progressive scleral necrosis secondary to plaque radiotherapy used for uveal malignant melanoma management. METHODS: In this case series, 4 patients with progressive scleral necrosis after Ru-106 plaque radiotherapy underwent corneal patch grafts with the anterior corneal button from Descemet stripping automated endothelial keratoplasty donor tissue to strengthen the sclera and to improve appearance of the eye. RESULTS: Ciliary body involvement was evident in all cases. All 4 patients had received radiation doses of 400 Gy or more to the tumor base. The mean time interval between plaque radiotherapy and scleral necrosis was 24.5 ± 7.5 months (range, 18-34 months). Successful results were achieved in all patients with tectonic graft. No patients experienced graft thinning, rejection, infection, or tumor recurrence in a mean follow-up of 28.5 ± 7.9 months (range, 20-39 months). CONCLUSIONS: Corneal patch graft by anterior corneal button from Descemet stripping automated endothelial keratoplasty donor tissue results in successful restoration of globe integrity and satisfactory cosmetic appearance in patients with scleral necrosis secondary to plaque radiotherapy.

Allergic eye disease, as in most forms of atopy, ranges in severity among individuals from immediate hypersensitivity to a severe and debilitating chronic disease. Dendritic cells play a key role in stimulating pathogenic T cells in allergen re-exposure, or secondary responses. However, molecular cues by dendritic cells underpinning allergic T cell response levels and the impact that this control has on consequent severity of allergic disease are poorly understood. Here, we show that a deficiency in thrombospondin-1, a matricellular protein known to affect immune function, has subsequent effects on downstream T cell responses during allergy, as revealed in an established mouse model of allergic eye disease. More specifically, we demonstrate that a thrombospondin-1 deficiency specific to dendritic cells leads to heightened secondary T cell responses and consequent clinical disease. Interestingly, whereas thrombospondin-1-deficient dendritic cells augmented activity of allergen-primed T cells, this increase was not recapitulated with naïve T cells in vitro. The role of dendritic cell-derived thrombospondin-1 in regulating secondary allergic T cell responses was confirmed in vivo, as local transfer of thrombospondin-1-sufficient dendritic cells to the ocular mucosa of thrombospondin-1 null hosts prevented the development of augmented secondary T cell responses and heightened allergic eye disease clinical responses. Finally, we demonstrate that topical instillation of thrombospondin-1-derived peptide reduces T cell activity and clinical progression of allergic eye disease. Taken together, this study reveals an important modulatory role of dendritic cell-derived thrombospondin-1 on secondary allergic T cell responses and suggests the possible dysregulation of dendritic cell-derived thrombospondin-1 expression as a factor in allergic eye disease severity.

PURPOSE: To assess whether stereopsis outcomes of patients with accommodative esotropia with high accommodative convergence/accommodation relationship (AC/A) were improved after treatment with bifocal glasses compared with single-vision lenses. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with high AC/A accommodative esotropia; evidence of stereopsis, binocularity (on Worth 4-dot testing), or improvement in near angle with +3.00 D lenses; and at least 4 years of records available for review, who were seen in the Department of Ophthalmology at Boston Children's Hospital between 2006 and 2014. METHODS: Use of bifocal or single-vision glasses. Charts were reviewed retrospectively. Stereopsis was log transformed for statistical analysis. Linear (for stereopsis) or logistic (for surgery) regression was used to control for confounders. MAIN OUTCOME MEASURES: Stereopsis at final follow-up, difference in stereopsis between final and initial visits, and progression to strabismus surgery. Secondary outcomes included final near and distance deviations. RESULTS: Of the 180 patients who met inclusion criteria, 77 used bifocals and 103 used single-vision lenses. Bifocals did not improve stereopsis outcomes compared with single-vision lenses. In both groups, stereopsis was similar at the initial and final visits, with similar improvement in both groups. Children in the bifocal group had a 3.6-fold higher rate of strabismus surgery than children in the single-lens group (P = 0.04.) Additionally, children in the bifocal group had near deviations 4 PD larger than those with single lenses at final follow-up, even after controlling for age and initial deviation (P = 0.02). These results did not change if surgical patients were eliminated or in the subgroup with initial distance deviation of 0 PD in full hyperopic correction. CONCLUSIONS: Despite their widespread use, there is no evidence that bifocals improve outcomes in children with accommodative esotropia with high AC/A. In our retrospective review, children with bifocals had higher surgical rates and a smaller improvement in near deviation over time. Although our results suggest that eliminating bifocals could reduce the cost and complexity of care while potentially improving quality, prospective, randomized controlled trials are needed to determine whether a change in practice is warranted.

UNLABELLED: Poor postnatal growth after preterm birth does not match the normal rapid growth in utero and is associated with preterm morbidities. Insulin-like growth factor 1 (IGF-1) axis is the major hormonal mediator of growth in utero, and levels of IGF-1 are often very low after preterm birth. We reviewed the role of IGF-1 in foetal development and the corresponding preterm perinatal period to highlight the potential clinical importance of IGF-1 deficiency in preterm morbidities. CONCLUSION: There is a rationale for clinical trials to evaluate the potential benefits of IGF-1 replacement in very preterm infants.

Endomucin is a membrane-bound glycoprotein expressed luminally by endothelial cells that line postcapillary venules, a primary site of leukocyte recruitment during inflammation. Here we show that endomucin abrogation on quiescent endothelial cells enables neutrophils to adhere firmly, via LFA-1-mediated binding to ICAM-1 constitutively expressed by endothelial cells. Moreover, TNF-α stimulation downregulates cell surface expression of endomucin concurrent with increased expression of adhesion molecules. Adenovirus-mediated expression of endomucin under inflammatory conditions prevents neutrophil adhesion in vitro and reduces the infiltration of CD45(+) and NIMP-R14(+) cells in vivo. These results indicate that endomucin prevents leukocyte contact with adhesion molecules in non-inflamed tissues and that downregulation of endomucin is critical to facilitate adhesion of leukocytes into inflamed tissues.