A 56-year-old woman presented with periocular nodules that were clinically suspected to be neurofibromas. Histopathologic examination of excised nodules revealed a pronounced granulomatous reaction to a foreign material that was composed of glossy polygonal palely eosinophilic fragments. These fragments were outlined in red with Masson trichrome, stained gray with the elastic stain, and were uniformly red with Gomori methenamine silver staining. The histopathologic appearance was consistent with a granulomatous reaction to Dermalive facial filler. Postoperatively the patient admitted that she had filler injections many years earlier in another country, and that nodules appeared 1 year after injection. Treatment with steroids, intralesional immunosuppressive agents and surgery had been previously attempted to eradicate the nodules. The literature pertaining to granulomatous reactions to Dermalive and related hybrid facial fillers is reviewed and treatment options are discussed. This report is the first to illustrate the unique histopathologic staining characteristics of Dermalive, which may be useful to ophthalmic pathologists in identifying this uncommon foreign material.

Retinal neuronal abnormalities occur before vascular changes in diabetic retinopathy. Accumulating experimental evidence suggests that neurons control vascular pathology in diabetic and other neovascular retinal diseases. Therefore, normalizing neuronal activity in diabetes may prevent vascular pathology. We investigated whether fibroblast growth factor 21 (FGF21) prevented retinal neuronal dysfunction in insulin-deficient diabetic mice. We found that in diabetic neural retina, photoreceptor rather than inner retinal function was most affected and administration of the long-acting FGF21 analog PF-05231023 restored the retinal neuronal functional deficits detected by electroretinography. PF-05231023 administration protected against diabetes-induced disorganization of photoreceptor segments seen in retinal cross section with immunohistochemistry and attenuated the reduction in the thickness of photoreceptor segments measured by optical coherence tomography. PF-05231023, independent of its downstream metabolic modulator adiponectin, reduced inflammatory marker interleukin-1β (IL-1β) mRNA levels. PF-05231023 activated the AKT-nuclear factor erythroid 2-related factor 2 pathway and reduced IL-1β expression in stressed photoreceptors. PF-05231023 administration did not change retinal expression of vascular endothelial growth factor A, suggesting a novel therapeutic approach for the prevention of early diabetic retinopathy by protecting photoreceptor function in diabetes.

Cosmetic products, such as mascara, eye shadow, eyeliner and eye makeup remover are used extensively to highlight the eyes or clean the eyelids, and typically contain preservatives to prevent microbial growth. These preservatives include benzalkonium chloride (BAK) and formaldehyde (FA)-releasing preservatives. We hypothesize that these preservatives, at concentrations (BAK = 1 mg/ml; FA = 0.74 mg/ml) approved for consumer use, are toxic to human ocular surface and adnexal cells. Accordingly, we tested the influence of BAK and FA on the morphology, survival, and proliferation and signaling ability of immortalized human meibomian gland (iHMGECs), corneal (iHCECs) and conjunctival (iHConjECs) epithelial cells. iHMGECs, iHCECs and iHConjECs were cultured with different concentrations of BAK (5 μg/ml to 0.005 μg/ml) or FA (1 mg/ml to 1 μg/ml) under basal, proliferating or differentiating conditions up to 7 days. We used low BAK levels, because we found that 0.5 mg/ml and 50 μg/ml BAK killed iHMGECs within 1 day after a 15 min exposure. Experimental procedures included analyses of cell appearance, cell number, and neutral lipid content (LipidTox), lysosome accumulation (LysoTracker) and AKT signaling in all 3 cell types. Our results demonstrate that BAK and FA cause dose-dependent changes in the morphology, survival, proliferation and AKT signaling of iHMGECs, iHCECs and iHConjECs. Many of the concentrations tested induced cell atrophy, poor adherence, decreased proliferation and death, after 5 days of exposure. Cellular signaling, as indicated by AKT phosphorylation after 15 (FA) or 30 (BAK) minutes of treatment, was also reduced in a dose-dependent fashion in all 3 cell types, irrespective of whether cells had been cultured under proliferating or differentiating conditions. Our results support our hypothesis and demonstrate that the cosmetic preservatives, BAK and FA, exert many toxic effects on cells of the ocular surface and adnexa.

Converging evidence suggests that the perception of auditory pitch exhibits a characteristic spatial organization. This pitch-space association can be demonstrated experimentally by the Spatial Musical Association of Response Codes (SMARC) effect. This is characterized by faster response times when a low-positioned key is pressed in response to a low-pitched tone, and a high-positioned key is pressed in response to a high-pitched tone. To investigate whether the development of this pitch-space association is mediated by normal visual experience, we tested a group of early blind individuals on a task that required them to discriminate the timbre of different instrument sounds with varying pitch. Results revealed a comparable pattern in the SMARC effect in both blind participants and sighted controls, suggesting that the lack of prior visual experience does not prevent the development of an association between pitch height and vertical space.

PURPOSE: To examine the efficacy and complications of laser peripheral iridotomy (LPI) in subjects with primary angle closure (PAC). METHODS: Literature searches in the PubMed and Cochrane databases were last conducted in August 2017 and yielded 300 unique citations. Of these, 36 met the inclusion criteria and were rated according to the strength of evidence; 6 articles were rated level I, 11 articles were rated level II, and 19 articles were rated level III. RESULTS: Reported outcomes were change in angle width, effect on intraocular pressure (IOP) control, disease progression, and complications. Most of the studies (29/36, 81%) included only Asian subjects. Angle width (measured by gonioscopy, ultrasound biomicroscopy, and anterior segment OCT) increased after LPI in all stages of angle closure. Gonioscopically defined persistent angle closure after LPI was reported in 2% to 57% of eyes across the disease spectrum. Baseline factors associated with persistent angle closure included narrower angle and parameters representing nonpupillary block mechanisms of angle closure, such as a thick iris, an anteriorly positioned ciliary body, or a greater lens vault. After LPI, further treatment to control IOP was reported in 0%-8% of PAC suspect (PACS), 42% to 67% of PAC, 21% to 47% of acute PAC (APAC), and 83%-100% of PAC glaucoma (PACG) eyes. Progression to PACG ranged from 0% to 0.3% per year in PACS and 0% to 4% per year in PAC. Complications after LPI included IOP spike (8-17 mmHg increase from baseline in 6%-10%), dysphotopsia (2%-11%), anterior chamber bleeding (30%-41%), and cataract progression (23%-39%). CONCLUSIONS: Laser peripheral iridotomy increases angle width in all stages of primary angle closure and has a good safety profile. Most PACS eyes do not receive further intervention, whereas many PAC and APAC eyes, and most PACG eyes, receive further treatment. Progression to PACG is uncommon in PACS and PAC. There are limited data on the comparative efficacy of LPI versus other treatments for the various stages of angle closure; 1 randomized controlled trial each demonstrated superiority of cataract surgery over LPI in APAC and of clear lens extraction over LPI in PACG or PAC with IOP above 30 mmHg.

PURPOSE: To determine whether botulinum toxin augments the effect of strabismus surgery in pediatric patients with large-angle infantile esotropia. DESIGN: Retrospective, comparative, case series. METHODS: Setting: Tertiary-care pediatric hospital. STUDY POPULATION: Patients with large-angle infantile esotropia. INTERVENTION: Treatment with botulinum toxin-augmented bilateral medial rectus muscle recessions ("augmented-surgery group") or traditional bilateral medial rectus muscle recessions ("surgery-only group"). MAIN OUTCOME MEASURE: The effect of surgery on ocular alignment at 4 months, measured in prism diopters of change per mm of surgery (PD/mm). RESULTS: There were 14 patients in the augmented-surgery group and 16 patients in the surgery-only group. The mean effect on alignment was significantly greater in the augmented-surgery group compared to the surgery-only group at 4 months (5.7 ± 1.3 vs 4.0 ± 1.4 PD/mm, P = .002) and at 1 year (5.4 ± 1.2 vs 3.7 ± 1.2 PD/mm, P = .002). There was a partial loss of treatment effect between 4 months and 1 year in both groups, which was similar in magnitude (P = .57). On linear regression, there was a trend toward a positive correlation between botulinum toxin dose and treatment effect, but this was not statistically significant (P = .09). CONCLUSIONS: Botulinum toxin augments the surgical effect of medial rectus muscle recession. Botulinum toxin-augmented surgery may be an alternative to traditional options for large-angle infantile esotropia. A surgical dosing table is proposed for this technique.

PURPOSE: To determine whether an association between Vitamin D and noninfectious ocular inflammation exists. METHODS: Retrospective case-control study with 765 patients (333 uveitis cases, 103 scleritis cases, 329 controls). Logistic regression models examined the relationship between hypovitaminosis D and ocular inflammation. RESULTS: The odds of having uveitis were 1.92 times higher for patients with hypovitaminosis D compared to patients with normal Vitamin D levels in the multivariate analysis [odds ratio (OR) = 1.92, 95% Confidence Interval (CI) = 1.36-2.72, p = 2.32 × 10]. A secondary analysis demonstrated that the odds of developing uveitis or scleritis were 5% lower and 4% lower, respectively, for every unit increase in Vitamin D level (uveitis: OR = 0.95, 95% CI = 0.94-0.97, p = 9.87 × 10; scleritis: OR = 0.96, 95% CI = 0.93-0.99, p = 0.009). CONCLUSION: Hypovitaminosis D was associated with increased risk of ocular inflammation in this retrospective study.

PURPOSE: To report the long-term surgical outcomes for a cohort of children with large-angle infantile esotropia. DESIGN: Multicenter, nonrandomized clinical study. METHODS: Setting: Two tertiary-care pediatric hospitals. STUDY POPULATION: Children with large-angle (≥55 prism diopters) infantile esotropia. INTERVENTION: Surgical treatment of infantile esotropia. MAIN OUTCOME MEASURE: Success rate at final follow-up (postoperative deviation ≤ 10 prism diopters and no need for retreatment). RESULTS: A total of 88 patients with large-angle infantile esotropia were treated during the 13-year study period. Treatment was bilateral medial rectus muscle recessions in 70 patients, botulinum toxin-augmented surgery in 15 patients, and 3-muscle surgery in 3 patients. After a mean follow-up of 40 months, 20 patients (23%) had a successful outcome compared to 68 treatment failures (77%). Of the 68 treatment failures, 59 had residual or recurrent esotropia and 9 had sequential exotropia. On multivariate logistic regression, treatment modality was the only factor significantly associated with a successful outcome. Specifically, patients treated with botulinum toxin-augmented surgery were more likely to have a successful outcome compared to patients treated with bilateral medial rectus muscle recessions. For the 26 patients (30%) who underwent retreatment, the mean number of procedures was 2.1, and 7 (27%) had a deviation of ≤10 prism diopters at final follow-up. CONCLUSIONS: The overall success rate for treatment of large-angle infantile esotropia was poor in this cohort, with most failures owing to recurrent or residual esotropia. Botulinum toxin-augmented surgery was associated with a higher success rate at final follow-up.

Objectives: Vancomycin-resistant Enterococcus faecium is a leading cause of MDR hospital infection. Two genetically definable populations of E. faecium have been identified: hospital-adapted MDR isolates (clade A) and vancomycin-susceptible commensal strains (clade B). VanN-type vancomycin resistance was identified in two isolates of E. faecium recovered from blood and faeces of an immunocompromised patient. To understand the genomic context in which VanN occurred in the hospitalized patient, the risk it posed for transmission in the hospital and its origins, it was of interest to determine where these strains placed within the E. faecium population structure. Methods: We obtained the genome sequence of the VanN isolates and performed comparative and functional genomics of the chromosome and plasmid content. Results: We show that, in these strains, VanN occurs in a genetic background that clusters with clade B E. faecium, which is highly unusual. We characterized the chromosome and the conjugative plasmid that carries VanN resistance in these strains, pUV24. This plasmid exhibits signatures of in-host selection on the vanN operon regulatory system, which are associated with a constitutive expression of vancomycin resistance. VanN resistance in clade B strains may go undetected by current methods. Conclusions: We report a case of vancomycin resistance in a commensal lineage of E. faecium responsible for an atypical bacteraemia in an immunocompromised patient. A reservoir of transferable glycopeptide resistance in the community could pose a concern for public health.