PURPOSE: To determine the utility of ophthalmology evaluation, dark-adapted threshold, and full-field electroretinogram for early detection of Usher syndrome in young patients with bilateral sensorineural hearing loss. METHODS: We identified 39 patients with secure genetic diagnoses of Usher Syndrome. Visual acuity, spherical equivalent, fundus appearance, dark-adapted threshold, and full-field electroretinogram results were summarized and compared to those in a group of healthy controls with normal hearing. In those Usher patients with repeated measures, regression analysis was done to evaluate for change in visual acuity and dark-adapted threshold with age. Spherical equivalent and full-field electroretinogram responses from dark- and light-adapted eyes were evaluated as a function of age. RESULTS: The majority of initial visual acuity and spherical equivalent results were within normal limits for age. Visual acuity and dark-adapted threshold worsened significantly with age in Usher type 1 but not in Usher type 2. At initial test, full-field electroretinogram responses from dark- and light-adapted eyes were abnormal in 53% of patients. Remarkably, nearly half of our patients (17% of Usher type 1 and 30% of Usher type 2) would have been missed by tests of retinal function alone if evaluated before age 10. CONCLUSIONS: Although there is an association of abnormal dark-adapted threshold and full-field electroretinogram at young ages in Usher patients, it appears that a small but important proportion of patients would not be detected by tests of retinal function alone. Thus, genetic testing is needed to secure a diagnosis of Usher syndrome.

PURPOSE: To describe the clinical and pathologic features of a case of epibulbar proliferative fasciitis and to compare it with other focal or diffuse myxoid lesions. METHODS: A clinical, histopathologic, and immunohistochemical analysis was performed. The clinical history, photographic documentation, history, and referred slides were reanalyzed. Additional immunohistochemical stains were performed at our institution. RESULTS: A 68-year-old woman developed over a week a brightly vascularized and focally hemorrhagic placoid lesion on the temporal side of the OS. She had had earlier augmentation breast surgery that had been mistakenly initially reported to us to be for breast carcinoma. Hematoxylin- and eosin-stained reactions revealed microscopically a spindle cell lesion with an intact nonkeratinizing epithelium and a background myxoid stroma with prominent capillaries and a light dispersion of small T-cell lymphocytes. Most striking among the spindle cells were some widely separated large atypical cells. The atypical cells were cytokeratin positive, but an expansive panel of immunohistochemical stains for breast carcinoma was negative. The lesion was diagnosed as proliferative fasciitis and has not recurred after 1-year follow up. CONCLUSION: A rapidly evolving conjunctival lesion is unlikely to be a primary or metastatic carcinoma. In the current case, the large ganglioform or rhabdomyoblast-like cells displayed diffuse cytokeratin positivity, still consistent with a mesenchymal or connective tissue cell lineage. Cytokeratin expression has been a finding previously reported in connective tissue tumors and in lymphoma cells. While the current lesion clinically resembles a conventional nodular fasciitis, the presence of the large atypical cells can lead to the misdiagnosis of a sarcoma, which typically displays a much higher Ki-67 proliferation index in comparison with nodular/proliferative fasciitis.

PURPOSE: To assess anatomic changes after laser peripheral iridotomy (LPI) and predictors of angle widening based on anterior segment (AS) OCT and angle opening based on gonioscopy. DESIGN: Prospective observational study. PARTICIPANTS: Primary angle-closure suspects (PACSs) 50 to 70 years of age. METHODS: Participants of the Zhongshan Angle Closure Prevention (ZAP) Trial underwent gonioscopy and AS-OCT imaging at baseline and 2 weeks after LPI. Primary angle-closure suspect was defined as the inability to visualize pigmented trabecular meshwork in 2 or more quadrants on static gonioscopy. Laser peripheral iridotomy was performed on 1 eye per patient in superior (between 11 and 1 o'clock) or temporal or nasal locations (at or below 10:30 or 1:30 o'clock). Biometric parameters in horizontal and vertical AS-OCT scans were measured and averaged. Linear and logistic regression modeling were performed to determine predictors of angle widening, defined as change in mean angle opening distance measured at 750 μm from the scleral spur (AOD750); poor angle widening, defined as the lowest quintile of change in mean AOD750; and poor angle opening, defined as residual PACS after LPI based on gonioscopy. MAIN OUTCOME MEASURES: Anatomic changes and predictors of angle widening and opening after LPI. RESULTS: Four hundred fifty-four patients were included in the analysis. Two hundred nineteen underwent superior LPI and 235 underwent temporal or nasal LPI. Significant changes were found among most biometric parameters (P < 0.006) after LPI, including greater AOD750 (P < 0.001). One hundred twenty eyes (26.4%) showed residual PACS after LPI. In multivariate regression analysis, superior LPI location (P = 0.004), smaller AOD750 (P < 0.001), and greater iris curvature (P < 0.001), were predictive of greater angle widening. Temporal or nasal LPI locations (odds ratio [OR], 2.60, P < 0.001) was predictive of poor angle widening. Smaller mean gonioscopy grade (OR, 0.34, 1-grade increment) was predictive of poor angle opening. CONCLUSIONS: Superior LPI location results in significantly greater angle widening compared with temporal or nasal locations in a Chinese population with PACS. This supports consideration of superior LPI locations to optimize anatomic changes after LPI.

We recently discovered that by changing environmental signals, differentiated immortalized human meibomian gland epithelial cells (IHMGECs) de-differentiate into proliferating cells. We also discovered that following exposure to appropriate stimuli, these proliferative cells re-differentiate into differentiated IHMGECs. We hypothesize that this plasticity of differentiated and proliferative IHMGECs is paralleled by very significant alterations in cellular gene expression. To begin to test this hypothesis, we compared the gene expression patterns of IHMGECs during differentiation and proliferation. IHMGECs were cultured for four days in either differentiating or proliferating media. After four days of culture, cells were processed for the analysis of gene expression by using Illumina BeadChips and bioinformatic software. Our study identified significant differences in the expression of more than 9200 genes in differentiated and proliferative IHMGECs. Differentiation was associated with significant increases in the expression of specific genes (e.g. S100 calcium binding protein P; 7,194,386-fold upregulation) and numerous ontologies (e.g. 83 biological process [bp] ontologies with ≥100 genes were upregulated), such as those related to development, transport and lysosomes. Proliferation also led to a significant rise in specific gene expressions (e.g. cathelicidin antimicrobial peptide; 859,100-fold upregulation) and many ontologies (115 biological process [bp] ontologies with ≥100 genes were upregulated), with most of the highly significant ontologies related to cell cycle (z scores > 13.9). Our findings demonstrate that gene expression in differentiated and proliferative IHMGECs is extremely different. These results may have significant implications for the regeneration of HMGECs and the reversal of MG dropout in MG dysfunction.

Pigment epithelium-derived factor (PEDF) is a widely expressed 50-kDa glycoprotein belonging to the serine protease inhibitor family, with well-established anti-inflammatory functions. Recently, we demonstrated the immunoregulatory role played by PEDF in dry eye disease (DED) by suppressing the maturation of antigen-presenting cells at the ocular surface following exposure to the desiccating stress. In this study, we evaluated the effect of PEDF on the immunosuppressive characteristics of regulatory T cells (Tregs), which are functionally impaired in DED. In the presence of PEDF, the in vitro cultures prevented proinflammatory cytokine (associated with type 17 helper T cells)-induced loss of frequency and suppressive phenotype of Tregs derived from normal mice. Similarly, PEDF maintained the in vitro frequency and enhanced the suppressive phenotype of Tregs derived from DED mice. On systemically treating DED mice with PEDF, moderately higher frequencies and significantly enhanced suppressive function of Tregs were observed in the draining lymphoid tissues, leading to the efficacious amelioration of the disease. Our results demonstrate that PEDF promotes the suppressive capability of Tregs and attenuates their type 17 helper T-cell-mediated dysfunction in DED, thereby playing a role in the suppression of DED.

PURPOSE: To describe 3 cases of corneal clearance after the use of topical rho-kinase inhibitor, netarsudil, in the setting of endothelial cell dysfunction in comparison to one case without corneal clearance after the use of netarsudil. METHODS: Four patients presenting to a busy academic clinical corneal practice with visual complaints from corneal edema secondary to endothelial cell dysfunction were treated with topical netarsudil one drop daily in the affected eye. RESULTS: Corneal clearance was observed in 1) a case of peripheral corneal edema in the setting of iridocorneal endothelial syndrome after 4 weeks on netarsudil, 2) a case of corneal edema in the setting of early penetrating keratoplasty graft failure after 2-week use of netarsudil, and 3) a case of corneal edema in the setting of chronic penetrating keratoplasty graft failure after 4-week use of netarsudil. Corneal clearance was not observed in a case of corneal edema in the setting of pseudophakic bullous keratopathy from previous complicated intraocular lens exchange surgery with placement of an anterior chamber intraocular lens after the use of netarsudil for 12 weeks. CONCLUSIONS: Addition of topical rho-kinase inhibitor in the form of netarsudil can result in corneal clearance in a variety of certain cases of endothelial cell dysfunction, not previously documented in the literature.

Purpose: One rehabilitation strategy taught to individuals with hemianopic field loss (HFL) is to make a large blind side scan to quickly identify hazards. However, it is not clear what the minimum threshold is for how large the scan should be. Using driving simulation, we evaluated thresholds (criteria) for gaze and head scan magnitudes that best predict detection safety. Methods: Seventeen participants with complete HFL and 15 with normal vision (NV) drove through 4 routes in a virtual city while their eyes and head were tracked. Participants pressed the horn as soon as they detected a motorcycle (10 per drive) that appeared 54 degrees eccentricity on cross-streets and approached toward the driver. Results: Those with HFL detected fewer motorcycles than those with NV and had worse detection on the blind side than the seeing side. On the blind side, both safe detections and early detections (detections before the hazard entered the intersection) could be predicted with both gaze (safe 18.5 degrees and early 33.8 degrees) and head (safe 19.3 degrees and early 27 degrees) scans. However, on the seeing side, only early detections could be classified with gaze (25.3 degrees) and head (9.0 degrees). Conclusions: Both head and gaze scan magnitude were significant predictors of detection on the blind side, but less predictive on the seeing side, which was likely driven by the ability to use peripheral vision. Interestingly, head scans were as predictive as gaze scans. Translational Relevance: The minimum scan magnitude could be a useful criterion for scanning training or for developing assistive technologies to improve scanning.

Nrf2, a transcription factor that regulates the response to oxidative stress, has been shown to rescue cone photoreceptors and slow vision loss in mouse models of retinal degeneration (rd). The retinal pigment epithelium (RPE) is damaged in these models, but whether it also could be rescued by Nrf2 has not been previously examined. We used an adeno-associated virus (AAV) with an RPE-specific (Best1) promoter to overexpress Nrf2 in the RPE of rd mice. Control rd mice showed disruption of the regular array of the RPE, as well as loss of RPE cells. Cones were lost in circumscribed regions within the cone photoreceptor layer. Overexpression of Nrf2 specifically in the RPE was sufficient to rescue the RPE, as well as the disruptions in the cone photoreceptor layer. Electron microscopy showed compromised apical microvilli in control rd mice but showed preserved microvilli in Best1-Nrf2-treated mice. The rd mice treated with Best1-Nrf2 had slightly better visual acuity. Transcriptome profiling showed that Nrf2 upregulates multiple oxidative defense pathways, reversing declines seen in the glutathione pathway in control rd mice. In summary, Nrf2 overexpression in the RPE preserves RPE morphology and survival in rd mice, and it is a potential therapeutic for diseases involving RPE degeneration, including age-related macular degeneration (AMD).