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Kalra G, Ichhpujani P, Thakur S, Singh RB, Sharma U, Kumar S. A pilot study for smartphone photography to assess bleb morphology and vasculature post-trabeculectomy. Int Ophthalmol 2021;41(2):483-490.Abstract
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.
Thulasi P, Saeed HN, Rapuano CJ, Hou JH, Appenheimer AB, Chodosh J, Kang JJ, Morrill AM, Vyas N, Zegans ME, Zuckerman R, Tu EY. Oral Miltefosine as Salvage Therapy for Refractory Acanthamoeba Keratitis. Am J Ophthalmol 2021;223:75-82.Abstract
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.
Wendt S, Abdullah Z, Barrett S, Daruwalla C, Go JA, Le B, Li E, Livingston C, Miller M, Nakhleh L, Pecha J, Pothula S, Pradhan S, Sathappan V, Shah A, Sonuyi A-M, Ugoh P, Wang Q, Weber N, Succar T, Blieden L, Mortensen P, Elkin Z, Sun G, Lee AG. A virtual COVID-19 ophthalmology rotation. Surv Ophthalmol 2021;66(2):354-361.Abstract
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.
Latifi G, Banafshe Afshan A, Houshang Beheshtnejad A, Zarei-Ghanavati M, Mohammadi N, Ghaffari R, Ghassemi H, Mohammadi SS, Kheirkhah A. Changes in Corneal Subbasal Nerves after Punctal Occlusion in Dry Eye Disease. Curr Eye Res 2021;46(6):777-783.Abstract
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.
Kumar V, Ali Shariati M, Mesentier-Louro L, Jinsook Oh A, Russano K, Goldberg JL, Liao YJ. Dual Specific Phosphatase 14 Deletion Rescues Retinal Ganglion Cells and Optic Nerve Axons after Experimental Anterior Ischemic Optic Neuropathy. Curr Eye Res 2021;46(5):710-718.Abstract
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.
Solaguren-Beascoa M, Bujakowska KM, Méjécase C, Emmenegger L, Orhan E, Neuillé M, Mohand-Saïd S, Condroyer C, Lancelot M-E, Michiels C, Demontant V, Antonio A, Letexier M, Saraiva J-P, Lonjou C, Carpentier W, Léveillard T, Pierce EA, Dollfus H, Sahel J-A, Bhattacharya SS, Audo I, Zeitz C. WDR34, a candidate gene for non-syndromic rod-cone dystrophy. Clin Genet 2021;99(2):298-302.Abstract
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.
Tomita Y, Cagnone G, Fu Z, Cakir B, Kotoda Y, Asakage M, Wakabayashi Y, Hellström A, Joyal J-S, Talukdar S, Smith LEH, Usui Y. Vitreous metabolomics profiling of proliferative diabetic retinopathy. Diabetologia 2021;64(1):70-82.Abstract
AIMS/HYPOTHESIS: Proliferative diabetic retinopathy (PDR) with retinal neovascularisation (NV) is a leading cause of vision loss. This study identified a set of metabolites that were altered in the vitreous humour of PDR patients compared with non-diabetic control participants. We corroborated changes in vitreous metabolites identified in prior studies and identified novel dysregulated metabolites that may lead to treatment strategies for PDR. METHODS: We analysed metabolites in vitreous samples from 43 PDR patients and 21 non-diabetic epiretinal membrane control patients from Japan (age 27-80 years) via ultra-high-performance liquid chromatography-mass spectrometry. We then investigated the association of a novel metabolite (creatine) with retinal NV in mouse oxygen-induced retinopathy (OIR). Creatine or vehicle was administered from postnatal day (P)12 to P16 (during induced NV) via oral gavage. P17 retinas were quantified for NV and vaso-obliteration. RESULTS: We identified 158 metabolites in vitreous samples that were altered in PDR patients vs control participants. We corroborated increases in pyruvate, lactate, proline and allantoin in PDR, which were identified in prior studies. We also found changes in metabolites not previously identified, including creatine. In human vitreous humour, creatine levels were decreased in PDR patients compared with epiretinal membrane control participants (false-discovery rate <0.001). We validated that lower creatine levels were associated with vascular proliferation in mouse retina in the OIR model (p = 0.027) using retinal metabolomics. Oral creatine supplementation reduced NV compared with vehicle (P12 to P16) in OIR (p = 0.0024). CONCLUSIONS/INTERPRETATION: These results suggest that metabolites from vitreous humour may reflect changes in metabolism that can be used to find pathways influencing retinopathy. Creatine supplementation could be useful to suppress NV in PDR. Graphical abstract.
Carreno-Galeano JT, Dohlman TH, Yin J, Dana R. Limbal Stem Cell Deficiency Associated With Herpes Keratitis. Cornea 2021;40(8):967-971.Abstract
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.
Chiou CA, Wang M, Taniguchi EV, Silva RNE, Khoroshilov A, Li D, Wang H, Greenstein SH, Brauner SC, Turalba AV, Pasquale LR, Shen LQ. Characterization of Prelaminar Wedge-Shaped Defects in Primary Open-Angle Glaucoma. Curr Eye Res 2021;46(6):895-902.Abstract
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.
Silva RNE, Chiou CA, Wang M, Devlin J, Li D, Lovelace S, Wang H, Greenstein SH, Brauner SC, Shen LQ. Quantification of the Peripapillary Microvasculature in Eyes with Glaucomatous Paracentral Visual Field Loss. Ophthalmol Glaucoma 2021;4(3):286-294.Abstract
PURPOSE: To quantify abnormalities in the peripapillary microvasculature in eyes with primary open-angle glaucoma (POAG) and paracentral visual field (VF) loss. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: Thirty-three POAG patients, including 15 with paracentral VF loss and 18 with peripheral VF loss, and 31 control participants underwent swept-source OCT angiography (OCTA) of the peripapillary region. METHODS: The POAG groups were matched by VF mean deviation (MD). The peripapillary microvasculature from the internal limiting membrane to the retinal nerve fiber layer (RNFL) interface was quantified within a 0.70-mm annulus around Bruch's membrane opening after removal of large vessels. Both vessel density (VD) and the integrated OCTA by ratio analysis signal (IOS) suggestive of flow were measured. Regional VD and IOS were measured from the affected hemisphere corresponding to the VF hemifield of more severe loss, which was used to calculate the paracentral total deviation (PaTD), or total deviation within the central 10°. One eye per participant was included. MAIN OUTCOME MEASURES: Difference in peripapillary OCTA measurements between paracentral and peripheral VF loss groups and correlation of peripapillary VD and IOS with PaTD. RESULTS: The POAG groups had matched VF MD (-3.1 ± 2.5 dB paracentral vs. -2.3 ± 2.0 dB peripheral; P = 0.31), did not differ in average RNFL thickness (71.1 ± 14.7 μm vs. 78.1 ± 15.0 μm; P = 0.55), but differed in age (59.2 ± 9.6 years paracentral vs. 67.4 ± 6.6 years peripheral; P = 0.02). Compared with control participants, both paracentral and peripheral VF loss groups showed reduced VD (P < 0.001 and P = 0.009, respectively) and IOS (P < 0.001 and P = 0.01, respectively) in the affected hemisphere. Compared with POAG eyes with peripheral VF loss, the paracentral group showed reduced peripapillary VD (38.0 ± 2.0%, 35.0 ± 2.2%, respectively; P = 0.001) and IOS (44.3 ± 3.1%, 40.4 ± 4.0%, respectively; P = 0.02) in the affected hemisphere. Among all POAG eyes, peripapillary VD and IOS of the affected hemisphere correlated significantly with functional measurement of paracentral loss (PaTD, r = 0.40, P = 0.02; r = 0.45, P = 0.008; respectively). These correlations remained significant after adjusting for age (r = 0.41, P = 0.02; r = 0.47, P = 0.01; respectively). CONCLUSIONS: Regional peripapillary microvasculature showed decreased VD and flow in POAG with paracentral loss, supporting its importance in this glaucoma subtype.
Pennington JD, Bleier BS, Freitag SK. Endoscopic endonasal resection of orbital schwannoma assisted with small-incision medial orbitotomy: case series and surgical technique. Orbit 2021;40(6):536-542.Abstract
PURPOSE: To describe a surgical approach for the resection of schwannomas occurring in the medial aspect of the orbit and to review a series of patients who underwent this novel technique. METHODS: This retrospective, non-comparative case series presents the surgical technique and outcomes of patients who underwent removal of a medial orbital schwannoma via an endoscopic endonasal approach combined with a small-incision medial orbitotomy by a team of two surgeons (BSB and SKF). Patient demographics, pre- and post-operative clinical examination findings, visual field testing, and radiographic studies were reviewed. Operative reports were reviewed for technical details and complications. RESULTS: The patients included a 12 year-old male, 73 year-old female and 8 year-old male. Indications for surgery included: decreased visual acuity, diplopia, proptosis and Humphrey visual field (HVF) deficit, in the presence of a medial orbital biopsy-proven schwannoma. The surgical approach in all three patients was primarily endoscopic endonasal. Additionally, two had transcaruncular orbitotomies and one had a small-incision medial lid crease orbitotomy to assist with lateral tumor dissection. Tumor resection was complete in one case and near-total in two cases. There were no intra-operative surgical complications. Average resected specimen volume was 3.41 cm3 ± 2.20. All patients had post-operative improvement in visual acuity (VA) and proptosis. Post-operative follow-up intervals were 27.5 months, 12.3 months and 3.5 months, respectively. CONCLUSION: Resection of orbital schwannomas using an endoscopic endonasal approach with small-incision medial transorbital assistance is a safe and effective option for a multidisciplinary surgical team.
Argüeso P. Galectins as Regulators of Corneal Inflammation. Curr Opin Physiol 2021;19:17-21.Abstract
The cornea is a transparent avascular tissue on the anterior segment of the eye responsible for providing refractive power and forming a protective barrier against the external environment. Infectious and inflammatory conditions can compromise the structure of the cornea, leading to visual impairment and blindness. Galectins are a group of β-galactoside-binding proteins expressed by immune and non-immune cells that play pivotal roles in innate and adaptive immunity. In this brief review, we discuss how different members of this family of proteins affect both pro-inflammatory and anti-inflammatory responses in the cornea, particularly in the context of infection, transplantation and wound healing. We further describe recent research showing beneficial effects of galectin-targeted therapy in corneal diseases.
Hainsworth DP, Gao X, Bebu I, Das A, Olmos de Koo L, Barkmeier AJ, Tamborlane W, Lachin JM, Aiello LP, and and of and Group DCCTF-up EDICR. Refractive Error and Retinopathy Outcomes in Type 1 Diabetes: The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study. Ophthalmology 2021;128(4):554-560.Abstract
PURPOSE: To determine the relationship between refractive error and diabetic retinopathy (DR). DESIGN: Clinical trial. PARTICIPANTS: Type I diabetes individuals with serial refractive error and DR stage measurements over 30 years in the Diabetes Control and Complications Trial (DCCT) and Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up study. METHODS: Stage of DR was measured every 6 months from standard fundus photographs, and refractive error was measured annually during the 6.5 years of DCCT; then, both were staggered every fourth year during EDIC with the full cohort measured at EDIC years 4 and 10. Outcomes of DR were 2- or 3-step progression, presence of proliferative DR (PDR), clinically significant macular edema (CSME), diabetic macular edema (DME), or ocular surgery. Myopia, emmetropia, and hyperopia were defined as a spherical equivalent of ≤-0.5, >-0.5 and <0.5, and ≥0.5, respectively. MAIN OUTCOME MEASURES: For each outcome separately, Cox proportional hazard (PH) models assessed the association between the refractive error status and the subsequent risk of that outcome, both without and with adjustment for potential risk factors. RESULTS: Hyperopia was associated with a higher risk of 2-step progression (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.05-1.59), 3-step progression (HR, 1.35; 95% CI, 1.05-1.73), and PDR (HR, 1.40; 95% CI, 1.02-1.92) compared with emmetropia in unadjusted models. These associations remained significant after adjustment for DCCT treatment group, cohort, age, sex, smoking, duration of diabetes, systolic and diastolic blood pressures, pulse, low-density lipoprotein, high-density lipoprotein, triglycerides, albumin excretion rate, and DCCT/EDIC mean updated hemoglobin A1c (HbA1c) (2-step progression: HR, 1.28; 95% CI, 1.03-1.58; 3-step progression: HR, 1.30; 95% CI, 1.00-1.68; PDR: HR, 1.38; 95% CI, 1.00-1.90). Myopia was not associated with any of the 5 DR outcomes in the unadjusted models and only marginally associated with 2-step progression (HR, 1.11; 95% CI, 1.00-1.24) in the adjusted models. CONCLUSIONS: Myopia is not associated with DR progression risk. Hyperopia is an independent risk factor for 2-step and 3-step DR progression and PDR.

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