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Tsoka P, Barbisan PR, Kataoka K, Chen XN, Tian B, Bouzika P, Miller JW, Paschalis EI, Vavvas DG. NLRP3 inflammasome in NMDA-induced retinal excitotoxicity. Exp Eye Res 2019;181:136-144.Abstract
N-methyl-D-aspartate (NMDA)-induced excitotoxicity is an acute form of experimental retinal injury as a result of overactivation of glutamate receptors. NLRP3 (nucleotide-binding domain, leucine-rich-repeat containing family, pyrin domain containing-3) inflammasome, one of the most studied sensors of innate immunity, has been reported to play a critical role in retinal neurodegeneration with controversial implications regarding neuroprotection and cell death. Thus far, it has not been elucidated whether NMDA-mediated excitotoxicity can trigger NLRP3 inflammasome in vivo. Moreover, it is unknown if NLRP3 is beneficial or detrimental to NMDA-mediated retinal cell death. Here, we employed a murine model of NMDA-induced retinal excitotoxicity by administering 100 nmoles of NMDA intravitreally, which resulted in massive TUNEL (TdT-dUTP terminal nick-end labelling) cell death in all retinal layers and especially in retinal ganglion cells (RGCs) 24 h post injection. NMDA insult in the retina potentiates macrophage/microglia cell infiltration, primes the NLRP3 inflammasome in a transcription-dependent manner and induces the expression of interleukin-1β (IL-1β). However, despite NLRP3 inflammasome upregulation, systemic deletion of Nlrp3 or Casp1 (caspase-1) did not significantly alter the NMDA-induced, excitotoxicity-mediated TUNEL retinal cell death at 24 h (acute phase). Similarly, the deletion of the two aforementioned genes did not alter the survival of the Brn3a (brain-specific homeobox/POU domain protein 3A) RGCs in a significant way at 3- or 7-days post injection (long-term phase). Our results indicate that NMDA-mediated retinal excitotoxicity induces immune cell recruitment and NLRP3 inflammasome activity even though inflammasome-mediated neuroinflammation is not a leading contributing factor to cell death in this type of retinal injury.
Raghuram A, Cotter S, Gowrisankaran S, Kanji J, Howell DR, Meehan WP, Shah AS. Post-Concussion: Receded Near Point of Convergence is Not Diagnostic of Convergence Insufficiency. Am J Ophthalmol 2019;Abstract
PURPOSE: To determine the frequency of receded near point of convergence (NPC) in patients with chronic concussion-related symptoms, and among those with receded NPC to enumerate the frequency of convergence insufficiency and other oculomotor disorders. STUDY: Design: Retrospective cross-sectional study METHODS: Clinic charts were retrospectively reviewed for the prior 3.5 years to identify all patients <21 years old who were >28 days post-concussion, had chronic concussion-related symptoms, had normal visual acuity, and received a comprehensive sensorimotor examination. The frequency of receded NPC and oculomotor diagnoses were determined. RESULTS: Of the 83 eligible patients, 74 (89%) had receded NPC. Of these, 70 (95%) had oculomotor disorders; 30 (41%) had disorders of accommodation only, 21 (28%) had convergence insufficiency and accommodation deficits, and 6 (8%) had convergence insufficiency only. Six (8%) had a convergence deficit other than convergence insufficiency (all with concurrent accommodative disorders), 4 (5%) had both a non-specific vergence dysfunction and accommodation deficits, 2 (3%) had convergence excess only, and 1 (1%) had both convergence excess and accommodative deficits. CONCLUSION: A receded NPC was present in the majority of young patients with chronic post-concussion symptoms. Associated with numerous underlying oculomotor dysfunctions, the clinical finding of a receded NPC is not synonymous with the diagnosis of convergence insufficiency. Because treatment options for the various oculomotor dysfunctions differ, it is prudent that these patients undergo a thorough examination of their vergence and accommodative systems so that an accurate diagnosis can be made and appropriate treatment prescribed.
Marmalidou A, Palioura S, Dana R, Kheirkhah A. Medical and surgical management of conjunctivochalasis. Ocul Surf 2019;Abstract
Conjunctivochalasis (CCH) is a bilateral conjunctival condition characterized by loose, redundant conjunctival folds, typically in the inferior bulbar conjunctiva. It is a common cause of ocular irritation, especially in older age. For asymptomatic CCH, no treatment is necessary. For treatment of symptomatic CCH, however, a variety of medical and surgical approaches are currently available, which will be thoroughly appraised in this review article. The first step in the management is medical therapy, which involves enhanced lubrication and use of anti-inflammatory medications. In refractory cases, a surgical approach may be undertaken for symptom relief. Several techniques have been described for this, with varying success rates. These include conjunctival cauterization, conjunctival excision, scleral fixation of the conjunctiva, conjunctival ligation, laser conjunctivoplasty, and radiowave electrosurgery. Among these, conjunctival cauterization and excision of the redundant conjunctiva, with or without tissue grafting, have gained popularity.
Hutcheon AEK, Zieske JD, Guo X. 3D in vitro model for human corneal endothelial cell maturation. Exp Eye Res 2019;184:183-191.Abstract
Corneal endothelium is a cellular monolayer positioned on the Descemet's membrane at the anterior cornea, and it plays a critical role in maintaining corneal clarity. Our present study examines the feasibility of utilizing our 3-dimensional (3D) corneal stromal construct, which consists of human corneal fibroblasts (HCF) and their self-assembled matrix, to observe the development and maturation of human corneal endothelial cells (HCEndoCs) in a co-culture model. Three-dimensional HCF constructs were created by growing the HCFs on Transwell membranes in Eagles' minimum essential medium (EMEM) + 10% FBS + 0.5 mM Vitamin C (VitC) for about 4 weeks. HCEndoCs, either primary (pHCEndoC) or cell line (HCEndoCL), were either seeded in chamber slides, directly on the Transwell membranes, or on the 3D HCF constructs and cultivated for 5 days or 2 weeks. The HCEndoCs that were seeded directly on the Transwell membranes were exposed indirectly to HCF by culturing the HCF on the plate beneath the membrane. Cultures were examined for morphology and ultrastructure using light and transmission electron microscopy (TEM). In addition, indirect-immunofluorescence microscopy (IF) was used to examine tight junction formation (ZO-1), maturation (ALDH1A1), basement membrane formation (Laminin), cell proliferation (Ki67), cell death (caspase-3), and fibrotic response (CTGF). As expected, both pHCEndoCs and HCEndoCLs formed monolayers on the constructs; however, the morphology of the HCEndoCLs appeared to be similar to that seen in vivo, uniform and closely packed, whereas the pHCEndoCs remained elongated. The IF data showed that laminin localization was present in the HCEndoCs' cytoplasm as cell-cell contact increased, and when they were grown in the 3D co-culture, the beginnings of what appears to be a continuous DM-like structure was observed. In addition, in co-cultures, ALDH1A1-positive HCEndoCs were present, ZO-1 expression localized within the tight junctions, minimal numbers of HCEndoCs were Ki67-or Caspase-3-positive, and CTGF was positive in both the HCEndoCs cytoplasm and the matrix of the co-culture. Also, laminin localization was stimulated in HCEndoCs upon indirect stimuli secreted by HCF. The present data suggests our 3D co-culture model is useful for studying corneal endothelium maturation in vitro since the co-culture promotes new DM-like formation, HCEndoCs develop in vivo-like characteristics, and the fibrotic response is activated. Our current findings are applicable to understanding the implications of corneal endothelial injection therapy, such as if the abnormal DM has to be removed from the patient, the newly injected endothelial cells will seed onto the wound area and deposit a new DM-like membrane. However, caution should be observed and as much of the normal DM should be left intact since removal of the DM can cause a posterior stromal fibrotic response.
Deiner MS, McLeod SD, Wong J, Chodosh J, Lietman TM, Porco TC. Google Searches and Detection of Conjunctivitis Epidemics Worldwide. Ophthalmology 2019;126(9):1219-1229.Abstract
PURPOSE: Epidemic and seasonal infectious conjunctivitis outbreaks can impact education, workforce, and economy adversely. Yet conjunctivitis typically is not a reportable disease, potentially delaying mitigating intervention. Our study objective was to determine if conjunctivitis epidemics could be identified using Google Trends search data. DESIGN: Search data for conjunctivitis-related and control search terms from 5 years and countries worldwide were obtained. Country and term were masked. Temporal scan statistics were applied to identify candidate epidemics. Candidates then were assessed for geotemporal concordance with an a priori defined collection of known reported conjunctivitis outbreaks, as a measure of sensitivity. PARTICIPANTS: Populations by country that searched Google's search engine using our study terms. MAIN OUTCOME MEASURES: Percent of known conjunctivitis outbreaks also found in the same country and period by our candidate epidemics, identified from conjunctivitis-related searches. RESULTS: We identified 135 candidate conjunctivitis epidemic periods from 77 countries. Compared with our a priori defined collection of known reported outbreaks, candidate conjunctivitis epidemics identified 18 of 26 (69% sensitivity) of the reported country-wide or island nationwide outbreaks, or both; 9 of 20 (45% sensitivity) of the reported region or district-wide outbreaks, or both; but far fewer nosocomial and reported smaller outbreaks. Similar overall and individual sensitivity, as well as specificity, were found on a country-level basis. We also found that 83% of our candidate epidemics had start dates before (of those, 20% were more than 12 weeks before) their concurrent reported outbreak's report issuance date. Permutation tests provided evidence that on average, conjunctivitis candidate epidemics occurred geotemporally closer to outbreak reports than chance alone suggests (P < 0.001) unlike control term candidates (P = 0.40). CONCLUSIONS: Conjunctivitis outbreaks can be detected using temporal scan analysis of Google search data alone, with more than 80% detected before an outbreak report's issuance date, some as early as the reported outbreak's start date. Future approaches using data from smaller regions, social media, and more search terms may improve sensitivity further and cross-validate detected candidates, allowing identification of candidate conjunctivitis epidemics from Internet search data potentially to complementarily benefit traditional reporting and detection systems to improve epidemic awareness.
Baker CW, Glassman AR, Beaulieu WT, Antoszyk AN, Browning DJ, Chalam KV, Grover S, Jampol LM, Jhaveri CD, Melia M, Stockdale CR, Martin DF, Sun JK, Sun JK. Effect of Initial Management With Aflibercept vs Laser Photocoagulation vs Observation on Vision Loss Among Patients With Diabetic Macular Edema Involving the Center of the Macula and Good Visual Acuity: A Randomized Clinical Trial. JAMA 2019;Abstract
Importance: Intravitreous injections of antivascular endothelial growth factor agents are effective for treating diabetic macular edema (DME) involving the center of the macula (center-involved DME [CI-DME]) with visual acuity impairment (20/32 or worse). The best approach to treating patients with CI-DME and good visual acuity (20/25 or better) is unknown. Objective: To compare vision loss at 2 years among eyes initially managed with aflibercept, laser photocoagulation, or observation. Design, Setting, and Participants: Randomized clinical trial conducted at 91 US and Canadian sites among 702 adults with type 1 or type 2 diabetes. Participants had 1 study eye with CI-DME and visual acuity of 20/25 or better. The first participant was randomized on November 8, 2013, and the final date of follow-up was September 11, 2018. Interventions: Eyes were randomly assigned to 2.0 mg of intravitreous aflibercept (n = 226) as frequently as every 4 weeks, focal/grid laser photocoagulation (n = 240), or observation (n = 236). Aflibercept was required for eyes in the laser photocoagulation or observation groups that had decreased visual acuity from baseline by at least 10 letters (≥ 2 lines on an eye chart) at any visit or by 5 to 9 letters (1-2 lines) at 2 consecutive visits. Main Outcomes and Measures: The primary outcome was at least a 5-letter visual acuity decrease from baseline at 2 years. Antiplatelet Trialists' Collaboration adverse events (defined as myocardial infarction, stroke, or vascular or unknown death) were reported. Results: Among 702 randomized participants (mean age, 59 years; 38% female [n=264]), 625 of 681 (92% excluding deaths) completed the 2-year visit. For eyes with visual acuity that decreased from baseline, aflibercept was initiated in 25% (60/240) and 34% (80/326) in the laser photocoagulation and observation groups, respectively. At 2 years, the percentage of eyes with at least a 5-letter visual acuity decrease was 16% (33/205), 17% (36/212), and 19% (39/208) in the aflibercept, laser photocoagulation, and observation groups, respectively (aflibercept vs laser photocoagulation risk difference, -2% [95% CI, -9% to 5%]; relative risk, 0.88 [95% CI, 0.57-1.35; P = .79]; aflibercept vs observation risk difference, -3% [95% CI, -11% to 4%]; relative risk, 0.83 [95% CI, 0.55-1.27; P = .79]; laser photocoagulation vs observation risk difference, -1% [95% CI, -9% to 6%]; relative risk, 0.95 [95% CI, 0.64-1.41; P = .79]). Antiplatelet Trialists' Collaboration vascular events occurred in 15 (7%), 13 (5%), and 8 (3%) participants in the aflibercept, laser photocoagulation, and observation groups. Conclusions and Relevance: Among eyes with CI-DME and good visual acuity, there was no significant difference in vision loss at 2 years whether eyes were initially managed with aflibercept or with laser photocoagulation or observation and given aflibercept only if visual acuity worsened. Observation without treatment unless visual acuity worsens may be a reasonable strategy for CI-DME. Trial Registration: ClinicalTrials.gov Identifier: NCT01909791.
Wladis EJ, Aakalu VK, Tao JP, Sobel RK, Freitag SK, Foster JA, Mawn LA. Monocanalicular Stents in Eyelid Lacerations: A Report by the American Academy of Ophthalmology. Ophthalmology 2019;126(9):1324-1329.Abstract
PURPOSE: To determine the efficacy and complication rates of monocanalicular stents in the setting of canalicular lacerations. METHODS: A literature search was performed in May 2018 in the PubMed database to identify all English-language reports of monocanalicular stenting to address canalicular lacerations. Studies that did not include at least 10 patients with at least 3 months of follow-up evaluation after surgery were excluded. Ninety-nine articles were identified, and 15 of these met criteria for data abstraction and were included in this assessment. The panel methodologist (V.K.A.) evaluated the quality of evidence and assigned a level-of-evidence rating to each of these studies. RESULTS: All 15 studies were rated as level III evidence. Anatomic and functional success rates after surgery ranged from 68% to 100% and 79% to 100%, respectively. Stents were generally well tolerated, although extrusion rates varied from 0% to 29%. CONCLUSIONS: Only level III evidence was available, and studies were not powered to detect differences between groups for rare complications or failure. Monocanalicular stents seem to be efficacious and well tolerated in the management of canalicular lacerations. Potential complications include extrusion (most commonly), tube displacement, granuloma, ectropion, slit punctum, fistula, and infection. Further comparative studies would help to identify the optimal time for device removal and to directly compare monocanalicular with bicanalicular stents.
Sayres R, Taly A, Rahimy E, Blumer K, Coz D, Hammel N, Krause J, Narayanaswamy A, Rastegar Z, Wu D, Xu S, Barb S, Joseph A, Shumski M, Smith J, Sood AB, Corrado GS, Peng L, Webster DR. Using a Deep Learning Algorithm and Integrated Gradients Explanation to Assist Grading for Diabetic Retinopathy. Ophthalmology 2019;126(4):552-564.Abstract
PURPOSE: To understand the impact of deep learning diabetic retinopathy (DR) algorithms on physician readers in computer-assisted settings. DESIGN: Evaluation of diagnostic technology. PARTICIPANTS: One thousand seven hundred ninety-six retinal fundus images from 1612 diabetic patients. METHODS: Ten ophthalmologists (5 general ophthalmologists, 4 retina specialists, 1 retina fellow) read images for DR severity based on the International Clinical Diabetic Retinopathy disease severity scale in each of 3 conditions: unassisted, grades only, or grades plus heatmap. Grades-only assistance comprised a histogram of DR predictions (grades) from a trained deep-learning model. For grades plus heatmap, we additionally showed explanatory heatmaps. MAIN OUTCOME MEASURES: For each experiment arm, we computed sensitivity and specificity of each reader and the algorithm for different levels of DR severity against an adjudicated reference standard. We also measured accuracy (exact 5-class level agreement and Cohen's quadratically weighted κ), reader-reported confidence (5-point Likert scale), and grading time. RESULTS: Readers graded more accurately with model assistance than without for the grades-only condition (P < 0.001). Grades plus heatmaps improved accuracy for patients with DR (P < 0.001), but reduced accuracy for patients without DR (P = 0.006). Both forms of assistance increased readers' sensitivity moderate-or-worse DR: unassisted: mean, 79.4% [95% confidence interval (CI), 72.3%-86.5%]; grades only: mean, 87.5% [95% CI, 85.1%-89.9%]; grades plus heatmap: mean, 88.7% [95% CI, 84.9%-92.5%] without a corresponding drop in specificity (unassisted: mean, 96.6% [95% CI, 95.9%-97.4%]; grades only: mean, 96.1% [95% CI, 95.5%-96.7%]; grades plus heatmap: mean, 95.5% [95% CI, 94.8%-96.1%]). Algorithmic assistance increased the accuracy of retina specialists above that of the unassisted reader or model alone; and increased grading confidence and grading time across all readers. For most cases, grades plus heatmap was only as effective as grades only. Over the course of the experiment, grading time decreased across all conditions, although most sharply for grades plus heatmap. CONCLUSIONS: Deep learning algorithms can improve the accuracy of, and confidence in, DR diagnosis in an assisted read setting. They also may increase grading time, although these effects may be ameliorated with experience.
Noble CW, Gangaputra SS, Thompson IA, Yuan A, Apolo AB, Lee J-M, Papaliodis GN, Kodati S, Bishop R, Magone TM, Sobrin L, Sen NH. Ocular Adverse Events following Use of Immune Checkpoint Inhibitors for Metastatic Malignancies. Ocul Immunol Inflamm 2019;:1-6.Abstract
PURPOSE: To report the clinical features, severity, and management of ocular immune-related adverse events (irAEs) in the setting of immune checkpoint inhibitor therapy for metastatic malignancies. METHODS: Retrospective chart review at three tertiary ophthalmology clinics. Electronic medical records were reviewed between 2000 and 2017 for patients with new ocular symptoms while undergoing checkpoint inhibition therapy. RESULTS: Eleven patients were identified. Ocular irAEs ranged from keratoconjunctivitis sicca to Vogt-Koyanagi-Harada-like findings. Average timing of irAEs from starting checkpoint inhibitor therapy was 15.7 weeks. Ocular inflammation was successfully controlled with corticosteroids in most cases, however three patients discontinue treatment as a result of ocular inflammation with decreased visual acuity, two discontinued due to progression of metastatic disease, and one discontinued due to severe systemic irAEs. CONCLUSION: We found a wide spectrum of ocular irAEs associated with immune checkpoint inhibitors. In most cases, ocular AEs did not limit ongoing cancer treatment.
Garza-Leon M, Amparo F, Ortíz G, de la Parra-Colin P, Sanchez-Huerta V, Beltran F, Hernandez-Quintela E. Translation and validation of the contact lens dry eye questionnaire-8 (CLDEQ-8) to the Spanish language. Cont Lens Anterior Eye 2019;42(2):155-158.Abstract
PURPOSE: To present the process of cultural and psychometric adaptation, and clinical validation of a new version in the Spanish language of the Contact Lens Dry Eye Questionnaire-8 (CLDEQ-8). MATERIALS AND METHODS: The translation-retro-translation method was applied to the CLDEQ-8 questionnaire. Two independent native Spanish-speaking translators adapted the questionnaire from English to Spanish, and then a committee of experienced clinicians (CE) evaluated the semantic equivalence and designed a Spanish version of the CLDEQ-8 questionnaire. The resulting translated version was tested conducting a pilot study in contact lens users and assessing their perception and overall understanding of the terminology. The results were analyzed and a final version was designed. The final version was retro-translated to English by a native English-speaking translator and compared with the original CLDEQ-8 version to confirm there were no meaningful differences. To clinically validate the new instrument, a prospective study was conducted to apply the new Spanish CLDEQ-8 to 50 contact lens users. RESULTS: Fifty patients were studied with an average age of 21.50 ± 1.66 years. The average CLDEQ-8 score was 13.28 ± 6.81 points (range 1-31). The internal consistency (Cronbach's alpha) was 0.89, with a corrected index of homogeneity >0.50 for all evaluated items. CONCLUSIONS: The process of trans-cultural adaptation of the questionnaire CLDEQ-8 resulted in the elaboration of a reliable and much needed instrument capable of measuring frequency and intensity of dry eye symptoms in Spanish-speaking contact lens users.
Berner D, Hoja U, Zenkel M, Ross JJ, Uebe S, Paoli D, Frezzotti P, Rautenbach RM, Ziskind A, Williams SE, Carmichael TR, Ramsay M, Topouzis F, Chatzikyriakidou A, Lambropoulos A, Sundaresan P, Ayub H, Akhtar F, Qamar R, Zenteno JC, Cruz-Aguilar M, Astakhov YS, Dubina M, Wiggs J, Ozaki M, Kruse FE, Aung T, Reis A, Khor CC, Pasutto F, Schlötzer-Schrehardt U. The protective variant rs7173049 at LOXL1 locus impacts on retinoic acid signaling pathway in pseudoexfoliation syndrome. Hum Mol Genet 2019;Abstract
LOXL1 (lysyl oxidase-like 1) has been identified as the major effect locus in pseudoexfoliation (PEX) syndrome, a fibrotic disorder of the extracellular matrix and frequent cause of chronic open-angle glaucoma. However, all known PEX-associated common variants show allele effect reversal in populations of different ancestry, casting doubt on their biological significance. Based on extensive LOXL1 deep sequencing, we report here the identification of a common noncoding sequence variant, rs7173049A>G, located downstream of LOXL1, consistently associated with a decrease in PEX risk (OR=0.63, p=6.33x10-31) in nine different ethnic populations. We provide experimental evidence for a functional enhancer-like regulatory activity of the genomic region surrounding rs7173049 influencing expression levels of ISLR2 (immunoglobulin superfamily containing leucine-rich repeat protein 2) and STRA6 (stimulated by retinoic acid receptor 6), apparently mediated by allele-specific binding of the transcription factor THRβ (thyroid hormone receptor beta). We further show that the protective rs7173049-G allele correlates with increased tissue expression levels of ISLR2 and STRA6 and that both genes are significantly downregulated in tissues of PEX patients together with other key components of the STRA6 receptor-driven retinoic acid signaling pathway. siRNA-mediated downregulation of retinoic acid signaling induces upregulation of LOXL1 and PEX-associated matrix genes in PEX-relevant cell types. These data indicate that dysregulation of STRA6 and impaired retinoid metabolismare involved in the pathophysiology of PEX syndrome and that the variant rs7173049-G, which represents the first common variant at the broad LOXL1 locus without allele effect reversal, mediates a protective effect through upregulation of STRA6 in ocular tissues.
Wang SK, Xue Y, Rana P, Hong CM, Cepko CL. Soluble CX3CL1 gene therapy improves cone survival and function in mouse models of retinitis pigmentosa. Proc Natl Acad Sci U S A 2019;116(20):10140-10149.Abstract
Retinitis pigmentosa (RP) is a disease that initially presents as night blindness due to genetic deficits in the rod photoreceptors of the retina. Rods then die, causing dysfunction and death of cone photoreceptors, the cell type that mediates high acuity and color vision, ultimately leading to blindness. We investigated immune responses in mouse models of RP and found evidence of microglia activation throughout the period of cone degeneration. Using adeno-associated vectors (AAVs), delivery of genes encoding microglial regulatory signals led to the identification of AAV serotype 8 (AAV8) soluble CX3CL1 (sCX3CL1) as a promising therapy for degenerating cones. Subretinal injection of AAV8-sCX3CL1 significantly prolonged cone survival in three strains of RP mice. Rescue of cones was accompanied by improvements in visual function. AAV8-sCX3CL1 did not affect rod survival, microglia localization, or inflammatory cytokine levels in the retina. Furthermore, although RNA sequencing of microglia demonstrated marked transcriptional changes with AAV8-sCX3CL1, pharmacological depletion of up to ∼99% of microglia failed to abrogate the effect of AAV8-sCX3CL1 on cone survival. These findings indicate that AAV8-sCX3CL1 can rescue cones in multiple mouse models of RP via a pathway that does not require normal numbers of microglia. Gene therapy with sCX3CL1 is a promising mutation-independent approach to preserve vision in RP and potentially other forms of retinal degeneration.
Takusagawa HL, Hoguet A, Junk AK, Nouri-Mahdavi K, Radhakrishnan S, Chen TC. Swept-Source OCT for Evaluating the Lamina Cribrosa: A Report by the American Academy of Ophthalmology. Ophthalmology 2019;126(9):1315-1323.Abstract
PURPOSE: To review the published literature on the use of swept-source (SS) OCT for evaluating the lamina cribrosa in glaucoma. METHODS: A PubMed and Cochrane Library literature search initially conducted on March 3, 2017, and updated on June 26, 2018, yielded a total of 64 articles. Articles that were reviews or that were not published in English were excluded, and 29 were found to fit the inclusion criteria. The panel methodologist then assigned a level of evidence rating to each study. Fifteen studies were rated level III, 14 studies were rated level II, and no studies were rated level I. RESULTS: Different aspects of the lamina cribrosa were studied using SS-OCT, including the anterior lamina cribrosa curvature, anterior lamina cribrosa depth, anterior lamina cribrosa insertions, laminar thickness, focal lamina cribrosa defects (FLCDs), and lamina cribrosa microarchitecture. In general, imaging of the anterior lamina can be achieved reliably, although shadowing from blood vessels at the neuroretinal rim remains an issue. Imaging of the posterior lamina can be achieved with varying levels of success. In glaucoma, there is posterior migration of the anterior lamina cribrosa insertions as well as increased thinning and posterior curvature of the lamina cribrosa. Focal lamina cribrosa defects appear more commonly in glaucoma, and this may hint at the pathogenesis of axonal damage. In addition, there may be remodeling of the microarchitecture of the lamina, resulting in more variable laminar pores. There are limited studies comparing SS-OCT with spectral-domain (SD) OCT with regard to imaging of the lamina, but the difference in image quality between enhanced depth imaging (EDI) with SD-OCT and SS-OCT seems minimal. CONCLUSIONS: Imaging of the lamina cribrosa using SS-OCT has demonstrated that the lamina cribrosa is likely biomechanically active and that significant changes occur in glaucoma. The diagnostic utility of SS-OCT for lamina cribrosa imaging is promising, but standardized nomenclature, automated measurements, and longitudinal studies with larger and more diverse sample sizes are needed.
Moein H-R, Saeed HN, Jacobs DS, Rapoport Y, Yoon MK, Shah AS, Khan H, Raoof D, Jurkunas UV. Exposure, entropion, and bilateral corneal ulceration in a newborn as a manifestation of chromosome 22 q11.2 duplication syndrome. Am J Ophthalmol Case Rep 2019;13:16-19.Abstract
Purpose: Chromosome 22q11.2 micro-duplication syndrome (MDS), is a rare autosomal dominant condition, with a highly variable phenotype that ranges from unremarkable and asymptomatic, to fatal due to cardiovascular defects. Hypertelorism, downslanting palpebral fissures, superior displacement of the eyebrows, and ptosis are the most commonly reported ocular manifestations. Here, we report a newborn with bilateral exposure, entropion, and corneal ulceration related to 22q11.2 MDS. Observation: A newborn girl presented with bilateral upper eyelid entropion, bilateral lower eyelid ectropion, and lagophthalmos. She subsequently developed bilateral corneal ulcers. Topical antibacterial drops, bandage contact lenses, medroxyprogesterone 1%, and fluorometholone 0.1%, together with partial tarsorrhaphy and correction of eyelid malposition, were used to treat the ulcers and address the underlying issues of exposure and entropion. Genetic testing revealed chromosome 22q11.2.MDS; further evaluation revealed systemic manifestations of this syndrome. The ocular surface healed well with gradual improvement of corneal opacification as well as bilateral partial tarsorrhaphy. Conclusion and importance: This report is the first that describes a newborn with 22q11.2 MDS presenting with sight-threatening corneal ulceration. Entropion, ectropion, and lagophthalmos were identified and treated, allowing for healing of the corneal surface. Genetic testing revealed a syndrome not known to be associated with eyelid abnormalities and corneal ulceration, but with other important systemic and ocular implications. Bilateral partial tarsorrhaphy should not be excluded as a treatment option for infants who fail more conservative measures for the treatment of exposure.

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