PURPOSE: Social media support groups can provide accessibility to advice and emotional regarding medical topics, such as retinal detachment repair, but this is almost universally provided by laypersons. We sought to determine how topics related to retinal detachment repair are associated with various emotional responses and the spread of misinformation, as identified through an online social media support group. METHODS: Retrospective observational study of the largest Facebook support group for retinal detachment from 03/19/2021 to 07/19/2021. Members of the support group that posted during the study period. Comments were coded by content (Pre-procedural, Peri-procedural Post procedural, Repeat procedures) and participant response (Emotional responses, Asking for medical advice, and Misinformation). Associations between content and responses were examined using Pearson's chi-squared test, two-sample t-test, and linear regression. RESULTS: Posts that included written comments from the study period were analyzed. Negative emotional responses appeared in 30% of posts and positive emotional responses were in 16% of posts. Misinformation was more likely to appear in pre-procedure posts (5.3% versus 1.4%, p = .03). Negative emotional responses trended towards being more common in topics related to repeat procedures (40% vs 28%), although this did not reach statistical significance (p = .06). CONCLUSIONS: Surgeons should be aware that patients frequently express negative experiences on this forum, asked for medical advice, even in the post-operative period, and that these posts generated high engagement. Misinformation may be propagated in support groups, though less commonly with regard to post-procedural questions.

PURPOSE: To determine the relationships of (1) tear osmolarity (TO) levels with the severity of signs and symptoms of dry eye disease (DED) and (2) changes in TO with changes in signs and symptoms. METHODS: Patients (N = 405) with moderate to severe DED in the Dry Eye Assessment and Management (DREAM) Study were evaluated at baseline and at six and 12 months. Associations of TO with signs and symptoms were evaluated using Pearson correlation coefficient (r) and regression models. RESULTS: The mean (standard deviation [SD]) TO was 303 (16) mOsm/L at baseline and 303 (18) mOsm/L at both six and 12 months. TO was higher in older patients (306 mOsm/L for ≥70 years vs. 300 mOsm/L for <50 years; P = 0.01) and those with Sjögren's disease (311 vs. 302 mOsm/L; P < 0.0001). TO did not differ between patients randomized to placebo and omega-3 fatty acid supplementation. TO was weakly correlated with conjunctival (r = 0.18; P < 0.001) and corneal staining scores (r = 0.17; P < 0.001), tear film break-up time (r = 0.06; P = 0.03), and Schirmer test score (r = -0.07; P = 0.02) but not with Ocular Surface Disease Index scores (r = 0.03; P = 0.40). Changes in signs and were not significantly correlated with change in TO at six or 12 months. CONCLUSIONS: Within DREAM, TO was weakly correlated with DED signs, explaining <5% variability in signs. Changes in tear osmolarity were not associated with changes in signs and symptoms of DED, indicating that the association may not be causal.

PURPOSE: To compare Early Treatment Diabetic Retinopathy Study (ETDRS) diabetic retinopathy (DR) severity on ultrawide field (UWF) colour imaging (CI) and UWF fluorescein angiography (FA). DESIGN: Cross-sectional retrospective review. SUBJECTS: Patients with diabetes mellitus and at least mild non-proliferative DR on UWF-CI. METHODS: UWF-CI and UWF-FA images acquired within 1 month of each other were evaluated independently using ETDRS DR Severity Scale (DRSS) for colour photography adapted for UWF-CI and UWF-FA. Extent of non-perfusion (NP, mm2) was determined from UWF-FA images. MAIN OUTCOME MEASURES: Agreement rate between DRSS on UWF-CI and UWF-FA. RESULTS: Images from 218 eyes of 137 patients with diabetes were evaluated. Agreement rate for DRSS between UWF-CI and UWF-FA was moderate to substantial (K=0.46, Kw=0.65). Over-all, DRSS was worse in 73 (33.5%) eyes on UWF-FA and in 16 (7.3%) on UWF-CI. Compared to UWF-CI, UWF-FA identified more severe DRSS in 26.5% (1 step) and 7.34% (≥2 steps) of eyes. DRSS was worse than UWF-FA in 56 (51.4%) in early DR (ETDRS levels 20-47, N=109) and 17 (15.6%) in eyes with severe DR (53 and higher, N=109). In this cohort, the extent of NP significantly increased as eyes approach moderate non-proliferative DR (levels 43-47, p=0.0065). CONCLUSION: When evaluating UWF-FA images using the ETDRS colour severity scale, DRSS is graded as more severe in a substantial number of eyes than when evaluating UWF-CI. It is uncertain how the DRSS levels using UWF-FA translate to clinical outcomes, but the additional lesions detected might provide added prognostic value. These and other recent data emphasise the need of obtaining outcome data based on UWF-FA and the potential need to develop DRSS specifically tailored for UWF-FA images.

The prevalence of asteroid hyalosis in adults ≥ 40 years old was 0.6–0.8% in the 2005–2008 National Health and Nutrition Examination Survey (NHANES). Older age and elevated serum creatinine were associated with the presence of asteroid hyalosis.

PURPOSE: To assess the effect of corneal scarring location on corneal nerve regeneration in patients with herpes simplex virus (HSV) keratitis in their affected and contralateral eyes over a 1-year period by in vivo confocal microscopy (IVCM), and to correlate these findings to corneal sensation measured by Cochet-Bonnet Esthesiometer. METHODS: Prospective, longitudinal, case-control study. Bilateral corneal nerve density and corneal sensation was analyzed centrally and peripherally in 24 healthy controls and 23 patients with unilateral HSV-related corneal scars using IVCM. RESULTS: In the central scar (CS) group, total nerve density in the central cornea remained significantly lower compared to controls at follow-up (11.05 ± 1.97mm/mm2, p < 0.001), and no significant nerve regeneration was observed (p = 0.090). At follow-up, total nerve density was not significantly different from controls in the central and peripheral cornea of peripheral scar (PS) group (all p > 0.05), and significant nerve regeneration was observed in central corneas (16.39 ± 2.39mm/mm2, p = 0.007) compared to baseline. In contralateral eyes, no significant corneal nerve regeneration was observed in central or peripheral cornea of patients with central scars or peripheral scars at 1-year follow-up, compared to baseline (p > 0.05). There was a positive correlation between corneal nerve density and sensation in both central (R = 0.53, p < 0.0001) and peripheral corneas (R = 0.27, p = 0.0004). In the CS group, the corneal sensitivity was <4 cm in 4 (30.8%) and 7 (53.8%) patients in the central and peripheral corneas at baseline, and in 5 (38.5%) and 2 subjects (15.4%) at follow-up, whereas in the PS group only 1 patient (10%) showed a corneal sensation < 4cm in the central cornea at baseline, and only 1 (10.0%), 3 (30.0%) and 1 (10.0%) patients at follow-up in the central, affected and opposite area of the cornea, respectively. CONCLUSION: The location of HSV scarring in the cornea affects the level of corneal nerve regeneration. Eyes with central corneal scar have a diminished capacity to regenerate nerves in central cornea, they show a more severe reduction in corneal sensation in the central and peripheral cornea that persist at follow-up, and they have a reduced capability to restore the corneal sensitivity above the cut-off of 4 cm. Thus, clinicians should be aware that CS patients would benefit from closer monitoring for potential complications associated with neurotrophic keratopathy, as they have a lower likelihood for nerve regeneration.

PURPOSE: Data from healthy eyes is needed to interpret optical coherence tomography angiography (OCTA) findings. However, very little normative data is available for wide-field swept-source OCTA (WF SS-OCTA), particularly 12 × 12-mm and disc-centered angiograms. Therefore, we aim to report quantitative metrics in a large sample of control eyes. METHODS: In this cross-sectional observational study, 482 eyes of 375 healthy adults were imaged on the 100 kHz Zeiss PLEX® Elite 9000 using protocols centered on the fovea (3 × 3, 6 × 6, and 12 × 12-mm) and optic disc (6 × 6 and 12 × 12-mm) between December 2018 and January 2022. The ARI Network (Zeiss Portal v5.4) was used to calculate vessel density (VD) and vessel skeletonized density (VSD) in the superficial capillary plexus, deep capillary plexus, and whole retina, as well as foveal avascular zone (FAZ) parameters. Mixed-effect multiple linear regression models were used for statistical analysis. RESULTS: The subjects' median age was 55 (38-63) years, and 201 (53.6%) were female. Greater age and worse best-corrected visual acuity (BCVA) were associated with significantly lower VD and VSD (p < 0.05). VD and VSD differed based on race and cataract status, but not sex, on some scan protocols (p < 0.05). FAZ circularity decreased with age, and FAZ dimensions differed based on race and ethnicity in certain scan protocols. CONCLUSIONS: We report a large database of parafoveal and peripapillary vascular metrics in several angiogram sizes. In referencing these values, researchers must consider characteristics such as age, race, and BCVA, but will have a valuable point of comparison for OCTA measurements in pathologic settings.

Usher syndrome (USH) is the most common form of hereditary deaf-blindness in humans. USH is a complex genetic disorder, assigned to three clinical subtypes differing in onset, course and severity, with USH1 being the most severe. Rodent USH1 models do not reflect the ocular phenotype observed in human patients to date; hence, little is known about the pathophysiology of USH1 in the human eye. One of the USH1 genes, USH1C, exhibits extensive alternative splicing and encodes numerous harmonin protein isoforms that function as scaffolds for organizing the USH interactome. RNA-seq analysis of human retinae uncovered harmonin_a1 as the most abundant transcript of USH1C. Bulk RNA-seq analysis and immunoblotting showed abundant expression of harmonin in Müller glia cells (MGCs) and retinal neurons. Furthermore, harmonin was localized in the terminal endfeet and apical microvilli of MGCs, presynaptic region (pedicle) of cones and outer segments (OS) of rods as well as at adhesive junctions between MGCs and photoreceptor cells (PRCs) in the outer limiting membrane (OLM). Our data provide evidence for the interaction of harmonin with OLM molecules in PRCs and MGCs and rhodopsin in PRCs. Subcellular expression and colocalization of harmonin correlate with the clinical phenotype observed in USH1C patients. We also demonstrate that primary cilia defects in USH1C patient-derived fibroblasts could be reverted by the delivery of harmonin_a1 transcript isoform. Our studies thus provide novel insights into PRC cell biology, USH1C pathophysiology and development of gene therapy treatment(s).

Clinical staging systems for diagnosis and treatment of diabetic retinopathy (DR) must closely relate to endpoints that are both relevant for patients and feasible for physicians to implement. Current DR staging systems for clinical eye care and research provide detailed phenotypic characterization to predict patient outcomes in diabetes but have limitations. Biochemical biomarkers provide a rich pool of potential candidates for new DR staging systems that can be readily measured in accessible fluids. Circulating biomarkers that are specific to the retina and relate to angiogenesis and inflammation have been suggested as relevant for DR. Although there is a lack of multi-ethnic studies evaluating circulatory biomarkers in DR, variability in circulatory biomarkers have been reported in people from different ethnic and racial backgrounds. Therefore, there is a need for future studies to evaluate individual or combinations of biomarkers in diverse populations with DR from different ethnic and racial backgrounds.

Artificial intelligence (AI) applications in healthcare will have a potentially far-reaching impact on patient care, however issues regarding algorithmic bias and fairness have recently surfaced. There is a recognized lack of diversity in the available ophthalmic datasets, with 45% of the global population having no readily accessible representative images, leading to potential misrepresentations of their unique anatomic features and ocular pathology. AI applications in retinal disease may show less accuracy with underrepresented populations that may further widen the gap of health inequality if left unaddressed. Beyond disease symptomatology, social determinants of health must be integrated into our current paradigms of disease understanding, with the goal of more personalized care. AI has the potential to decrease global healthcare inequality, but it will need to be based on a more diverse, transparent and responsible use of healthcare data.

Corneal transplant rejection primarily occurs due to T helper 1 (Th1) effector cell mediated immune response of the host toward allogeneic tissue. The evidence suggests that Type 1 migratory conventional CD103+ dendritic cells (CD103+DC1) acquire an immunosuppressive phenotype in the tumor environment; however, the involvement of CD103+DC1 in allograft survival continues to be an elusive question of great clinical significance in tissue transplantation. In this study, we assess the role of CD103+DC1 in suppressing Th1 alloreactivity against transplanted corneal allografts. The immunosuppressive function of CD103+DC1 has been extensively studied in non-transplantation settings. We found that host CD103+DC1 infiltrate the corneal graft and migrate to the draining lymph nodes (DLN) to suppress alloreactive CD4+ Th1 cells via the programmed death-ligand 1 (PD-L1/ PD-1) axis. The systemic depletion of CD103+ DC1 in allograft recipients leads to amplified Th1 activation, impaired Treg function, and increased frequency of allograft rejection. While allograft recipient Rag1 null mice reconstituted with naïve CD4+CD25- T cells efficiently generated peripheral Treg cells (pTreg), the CD103+DC1-depleted mice failed to generate pTreg. Furthermore, adoptive transfer of pTreg failed to rescue allografts in CD103+DC1-depleted recipients from rejection. These data demonstrate the critical role of CD103+DC1 in regulating host alloimmune responses. Short title: Role of CD103+ DCs in corneal allograft survival.