PURPOSE: To determine the clinical relevance of prelaminar wedge defects (PLWDs) detected by swept-source optical coherence tomography (SS-OCT) in primary open-angle glaucoma (POAG). MATERIALS AND METHODS: In this retrospective case-control study, PLWDs were defined as triangular-shaped defects at the surface of the optic nerve prelaminar tissue, not adjacent to blood vessels, present on cross-sectional SS-OCT scans. Two observers masked to diagnosis independently reviewed scans to detect PLWDs and lamina cribrosa defects. History of disc hemorrhage, occurring within 2 years prior to imaging, was obtained from chart review. One eye per subject was randomly selected. Two-sided t-tests, analysis of variance with Bonferroni correction, and multivariable logistic regression analysis were performed to explore demographic and clinical features associated with PLWDs. RESULTS: 40 POAG and 23 control eyes were included. PLWDS were found in 27.5% of POAG (n = 11) and 4.3% of controls (n = 1, p = .04). Eyes with repeat SS-OCT imaging (7 POAG and 0 controls) had persistent PLWDs. More POAG eyes with PLWDs had a history of disc hemorrhage (45.5%) than POAG eyes without PLWDs (3.4%, p = .004). On multivariable analysis, compared to POAG without PLWDs, POAG with PLWDs had increased odds of observed disc hemorrhage (OR = 21.6, 95% CI, 2.2-589.0, p = .02) after adjusting for age, gender, visual field mean deviation and maximum intraocular pressure (IOP). POAG with PLWDs had more lamina cribrosa defects (45.5%) than POAG without PLWDs (3.4%, p = .01) but did not differ significantly from controls (8.7%, p = .07). Compared to all patients without PLWDs, patients with PLWDs had increased odds of having lamina cribrosa defects (OR = 44.8; 95% CI, 6.3-703.6, p < .001) after adjusting for age, gender, and maximum IOP. CONCLUSIONS: PLWDs were more frequently found in POAG than control eyes and were associated with a history of disc hemorrhage and lamina cribrosa defects. PLWDs may be a useful imaging biomarker of glaucomatous damage.

PURPOSE: The current grading systems used for bleb morphology assessment in patients post-trabeculectomy are based on standardized slit-lamp photographs and anterior segment imaging devices. The lack of availability of these expensive and non-portable devices in resource-deficient settings is a significant deterrent in their widespread utilization for proper post-operative management. The rapidly evolving utilization of smartphone photography has significantly benefited diagnostics of posterior segment disorders and is now being increasingly utilized for monitoring anterior segment pathologies as well as post-surgical course. In this study, we study a novel use of smartphones for bleb photography for assessing the morphological characteristics as vascularity and microcysts. METHODS: In this pilot, observational study, we compared the trabeculectomy bleb images of five subjects, obtained by iPhone X (dual lens) and iPhone 6S (single lens). We captured two image sets with both smartphones first with a focussed torchlight and then with a built-in flash video light. RESULTS: The images resulting from the newer iPhone X were substantially superior than those from iPhone 6S. For the 12-megapixel dual-camera set-up on the iPhone X, the 1 × lens resulted in better images than the 2 × lens with contrast and overall clarity of the area of interest. While the macro-lens attachment had promising results at 1 × zoom, there is no added advantage of the macro-lens attachment as it resulted in considerable loss of image quality at twice the zoom. Using a 20 D lens helped attain higher magnification and better framing as it reduced the focussing distance needed to get sharp images. The images obtained from both smartphones were of higher quality when illuminated from an external source when compared to the native iPhone flash due to even exposure and fewer autofocus artefacts. CONCLUSION: Analyses of all image sets showed that the current generation in-built camera app on IOS and newer iPhone camera optics resulted in high-quality images of the ocular surface with high magnification without any loss in clarity.

PURPOSE: To evaluate corneal subbasal nerve plexus by in vivo confocal microscopy (IVCM) following punctal occlusion in patients with moderate to severe dry eye disease (DED). MATERIALS AND METHODS: Patients with grade 3 or 4 severity of DED based on Delphi Panel dry eye severity grading scheme were enrolled in the study. Permanent inferior punctal occlusion was performed. A comprehensive ophthalmic evaluation, including Ocular Surface Disease Index (OSDI) questionnaire, tear break-up time (TBUT), corneal fluorescein staining, conjunctival Rose bengal staining, Schirmer's test, and corneal sensation by Cochet-Bonnet esthesiometry, were performed at baseline, and 1 and 3 months after punctal occlusion. Furthermore, density and number of corneal subbasal nerves were evaluated by IVCM. RESULTS: Forty-one eyes of 23 patients with a mean age of 46.3 ± 9.0 years were enrolled. Corneal fluorescein staining, Rose bengal staining, and TBUT significantly improved at 3 months following punctal occlusion (p < .015). Corneal esthesiometry significantly increased at both postoperative visits (p < .03), and OSDI scores improved only at 3-month follow-up (p < .005). Nerve density and total number significantly increased 3 months after punctal occlusion (p < .045). Baseline nerve density had significant correlations with TBUT, fluorescein staining, Rose bengal staining (p < .012), but not with esthesiometry, Schirmer scores, or OSDI scores (p > .329). CONCLUSIONS: Corneal subbasal nerve density and total number increased following punctal occlusion in patients with moderate to severe DED. These findings were associated with improvements in corneal sensation, and signs and symptoms of DED. This emphasizes the effect of punctal occlusion in regeneration of corneal subbasal nerve plexus.

PURPOSE: To describe the demographic features and clinical characteristics of patients with herpes keratitis (HK) and limbal stem cell deficiency (LSCD) and identify possible factors associated with development of LSCD after HK. METHODS: In this retrospective case-series study, records of patients with a clinical diagnosis of HK seen at Massachusetts Eye and Ear over a 5-year period were reviewed for evidence of LSCD. Patient demographics, medical history, treatment, and best-corrected visual acuities (BCVAs) were recorded. RESULTS: We identified 626 patients with HK. Fifty-seven had been diagnosed with LSCD (9.3%). Thirteen percent of patients with herpes zoster keratitis (N= 25) and 7% of patients with herpes simplex keratitis (N= 32) had LSCD (P = 0.01). Keratitis caused by herpes zoster virus [odds ratios (OR), 1.77; 95% confidence interval (CI), 0.97-3.19; P = 0.01], stromal involvement (OR, 2.28; 95% CI, 1.27-4.18; P = 0.02), and the use of topical antihypertensives (OR, 2.28; 95% CI, 1.27-4.18; P = 0.02) were found to be associated with a higher likelihood of developing LSCD. The final logarithm of the minimum angle of resolution (LogMAR) BCVA was significantly lower in patients with LSCD compared with those without LSCD with a mean BCVA of 1.34 ± 1.52 LogMar (∼20/200) as compared to 0.18 ± 0.54 LogMar (∼20/30 ± 20/60) in those patients without LSCD (P = 0.005). CONCLUSIONS: Our data suggest that HK may be a risk factor for development of LSCD. Patients with HK should be monitored for the development of LSCD to reduce the risk of chronic ocular surface morbidity.

The coronavirus (COVID-19) pandemic temporarily suspended medical student involvement in clinical rotations, resulting in the need to develop virtual clinical experiences. The cancellation of clinical ophthalmology electives and away rotations reduces opportunities for exposure to the field, to network with faculty, conduct research, and prepare for residency applications. We review the literature and discuss the impact and consequences of COVID-19 on undergraduate medical education with an emphasis on ophthalmic undergraduate medical education. We also discuss innovative learning modalities used from medical schools around the world during the COVID-19 pandemic such as virtual didactics, online cases, and telehealth. Finally, we describe a novel, virtual neuro-ophthalmology elective created to educate medical students on neuro-ophthalmology foundational principles, provide research and presentation opportunities, and build relationships with faculty members. These innovative approaches represent a step forward in further improving medical education in ophthalmology during COVID-19 pandemic and beyond.

PURPOSE: Understanding molecular changes is essential for designing effective treatments for nonarteritic anterior ischemic optic neuropathy (AION), the most common acute optic neuropathy in adults older than 50 years. We investigated changes in the mitogen-activated protein kinase (MAPK) pathway after experimental AION and focused on dual specificity phosphatase 14 (Dusp14), an atypical MAPK phosphatase that is downstream of Krüppel-like transcription factor (KLF) 9-mediated inhibition of retinal ganglion cell (RGC) survival and axonal regeneration. MATERIALS AND METHODS: We induced severe AION in a photochemical thrombosis model in adult C57BL/6 wild-type and Dusp14 knockout mice. For comparison, some studies were performed using an optic nerve crush model. We assessed changes in MAPK pathway molecules using Western blot and immunohistochemistry, measured retinal thickness using optical coherence tomography (OCT), and quantified RGCs and axons using histologic methods. RESULTS: Three days after severe AION, there was no change in the retinal protein levels of MAPK ERK1/2, phosphorylated-ERK1/2 (pERK1/2), downstream effector Elk-1 and phosphatase Dusp14 on Western blot. Western blot analysis of purified RGCs after a more severe model using optic nerve crush also showed no change in Dusp14 protein expression. Because of the known importance of the Dusp14 and MAPK pathway in RGCs, we examined changes after AION in Dusp14 knockout mice. Three days after AION, Dusp14 knockout mice had significantly increased pERK1/2+, Brn3A+ RGCs on immunohistochemistry. Three weeks after AION, Dusp14 knockout mice had significantly greater preservation of retinal thickness, increased number of Brn3A+ RGCs on whole mount preparation, and increased number of optic nerve axons compared with wild-type mice. CONCLUSIONS: Genetic deletion of Dusp14, a MAPK phosphatase important in KFL9-mediated inhibition of RGC survival, led to increased activation of MAPK ERK1/2 and greater RGC and axonal survival after experimental AION. Inhibiting Dusp14 or activating the MAPK pathway should be examined further as a potential therapeutic approach to treatment of AION. Abbreviations: AION: anterior ischemic optic neuropathy; Dusp14: dual specific phosphatase 14; ERK1/2: extracellular signal-regulated kinases 1/2; Elk-1: ETS Like-1 protein; GCC: ganglion cell complex; GCL: ganglion cell layer; inner nuclear layer; KO: knockout; MAPK: mitogen-activated phosphokinase; OCT: optical coherence tomography; RGC: retinal ganglion cell; RNFL: retinal nerve fiber layer.

OBJECTIVES: To evaluate a novel approach to determine the refractive target for patients undergoing cataract surgery who are dependent on therapeutic scleral lenses, to avoid the need for postoperative scleral lens replacement. METHODS: Retrospective single-surgeon case series. The target refraction for intraocular lens selection was determined by considering the effective scleral lens system power. This was calculated by adding the known scleral lens spherical power to the difference between the scleral lens base curve and the average keratometry value. RESULTS: Six eyes from three patients with moderate myopia or emmetropia with ocular graft versus host disease dependent on therapeutic scleral lenses underwent cataract surgery with intraocular lens selection based on this method. All six eyes had corrected visual acuities of 20/30 or better while wearing their previous scleral lenses at the postoperative week 1 visit. All six eyes resumed full-time scleral lens use 1 week after phacoemulsification and did not require scleral lens replacement. CONCLUSIONS: Using this method, patients requiring therapeutic scleral lenses can quickly experience optimal vision, comfort, and ocular surface protection 1 week after cataract surgery. These patients can continue to use their existing scleral lenses and avoid the costs and burdens associated with lens replacement.

Rod-cone dystrophy (RCD), also called retinitis pigmentosa, is characterized by rod followed by cone photoreceptor degeneration, leading to gradual visual loss. Mutations in over 65 genes have been associated with non-syndromic RCD explaining 60% to 70% of cases, with novel gene defects possibly accounting for the unsolved cases. Homozygosity mapping and whole-exome sequencing applied to a case of autosomal recessive non-syndromic RCD from a consanguineous union identified a homozygous variant in WDR34. Mutations in WDR34 have been previously associated with severe ciliopathy syndromes possibly associated with a retinal dystrophy. This is the first report of a homozygous mutation in WDR34 associated with non-syndromic RCD.

PURPOSE: To report a case series of patients with treatment-resistant Acanthamoeba keratitis (AK) using oral miltefosine, often as salvage therapy. DESIGN: Descriptive, retrospective multicenter case series. METHODS: We reviewed 15 patients with AK unresponsive to therapy who were subsequently given adjuvant systemic miltefosine between 2011 and 2017. The main outcome measures were resolution of infection, final visual acuity, tolerance of miltefosine, and clinical course of disease. RESULTS: All patients were treated with biguanides and/or diamidines or azoles without resolution of disease before starting miltefosine. Eleven of 15 patients retained count fingers or better vision, and all were considered disease free at last follow-up. Eleven of 15 patients had worsening inflammation with miltefosine, with 10 of them improving with steroids. Six patients received multiple courses of miltefosine. Most tolerated oral miltefosine well, with mild gastrointestinal symptoms as the most common systemic side effect. CONCLUSIONS: Oral miltefosine is a generally well-tolerated treatment adjuvant in patients with refractory AK. The clinician should be prepared for a steroid-responsive inflammatory response frequently encountered during the treatment course.