2021

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Rageh A, Ashraf M, Fleming A, Silva PS. Automated Microaneurysm Counts on Ultrawide Field Color and Fluorescein Angiography Images. Semin Ophthalmol 2021;36(4):315-321.Abstract
BACKGROUND: The severity and extent of microaneurysms (MAs) have been used to determine diabetic retinopathy (DR) severity and estimate the risk of DR progression over time. The recent introduction of ultrawide field (UWF) imaging has allowed ophthalmologists to readily image nearly the entire retina. Manual counting of MAs, especially on UWF images, is laborious and time-consuming, limiting its potential use in clinical settings. Automated MA counting techniques are potentially more accurate and reproducible compared to manual methods. METHOD: Review of available literature on current techniques of automated MA counting techniques on both ultrawide field (UWF) color images (CI) and fluorescein angiography (FA) images. RESULTS: Automated MA counting techniques on UWF images are still in the early phases of development with UWF-FA counts being further along. Early studies have demonstrated that these techniques are accurate and reproducible. CONCLUSION: Automated techniques may be an appropriate option for detecting and quantifying MAs on UWF images, especially in eyes with earlier DR severity. Larger studies are needed to appropriately validate these techniques and determine if they add substantially to clinical practice compared to standard DR grading.
Rahimkhoei V, Jabbari N, Nourani A, Sharifi S, Akbari A. Potential small-molecule drugs as available weapons to fight novel coronavirus (2019-nCoV): A review. Cell Biochem Funct 2021;39(1):4-9.Abstract
Since the new coronavirus known as 2019-nCoV (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has widely spread in Wuhan, China, with severe pneumonia, scientists and physicians have made remarkable efforts to use various options such as monoclonal antibodies, peptides, vaccines, small-molecule drugs and interferon therapies to control, prevent or treatment infections of 2019-nCoV. However, no vaccine or drug has yet been confirmed to completely treat 2019-nCoV. In this review, we focus on the use of potential available small-molecule drug candidates for treating infections caused by 2019-nCoV.
Rashad R, Shanbhag SS, Kwan J, Chodosh J, Saeed S, Saeed HN. Chronic ocular complications in lamotrigine vs. trimethoprim-sulfamethoxazole induced Stevens-Johnson syndrome/toxic epidermal necrolysis. Ocul Surf 2021;21:16-18.Abstract
PURPOSE: The purpose of this study is to compare the severity of chronic ocular complications of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) induced by lamotrigine (LT) vs. trimethoprim-sulfamethoxazole (TS). METHODS: This retrospective cross-sectional study evaluated all SJS/TEN patients treated within our hospital network from 2008 to 2018. Inclusion criteria included patients with reactions identified as caused by either LT or TS, and patients with at least one ophthalmology follow up in the chronic phase (≥3 months from disease onset). Primary outcome measures included LogMAR best-corrected VA at most recent visit and the presence or absence of severe ocular complications (SOC). Secondary outcome measures included chronic ocular complication severity scores using a modified Sotozono scoring system. RESULTS: Forty-eight eyes of 24 patients were included in the study. The mean duration of follow-up was 39.50 ± 35.62 vs. 48.17 ± 33.09 months, respectively (p = 0.482). The LT group had worse average VA at the most recent visit (LogMAR VA; 0.508 vs. 0.041, p < 0.0001) and had a higher prevalence of SOCs (66.7% vs. 8.3%, p = 0.0038). The LT group scored worse on Sotozono chronic complications scores for the cornea (1.875 vs. 0.5, p = 0.0018), eyelid margin (5.583 vs.3.083, p = 0.0010), and overall condition (8.500 vs. 4.833, p = 0.0015). Sub-analyses showed that a moderate or severe acute ocular severity score was a significant predictor of chronic outcomes. CONCLUSIONS: Compared to patients with TS-induced SJS/TEN, patients with LT-induced SJS/TEN developed worse chronic ocular complications on several parameters. Future prospective studies are warranted to provide additional insight into the drug type as a predictor of chronic ocular complications.
Ratanawongphaibul K, Tsikata E, Zemplenyi M, Lee H, Margeta MA, Ondeck CL, Kim J, Pan BX, Petrakos P, Coleman AL, Yu F, de Boer JF, Chen TC. Earlier Detection of Glaucoma Progression Using High-Density 3-Dimensional Spectral-Domain OCT Optic Nerve Volume Scans. Ophthalmol Glaucoma 2021;4(6):604-616.Abstract
PURPOSE: To compare onset times of glaucoma progression among different glaucoma tests: disc photography (DP), visual field (VF) testing, 2-dimensional (2D) retinal nerve fiber layer (RNFL) thickness, and 3-dimensional (3D) spectral-domain (SD) OCT neuroretinal rim measurements. DESIGN: Prospective, longitudinal cohort study. PARTICIPANTS: One hundred twenty-four eyes of 124 patients with open-angle glaucoma. METHODS: Over a 5-year period, 124 patients with open-angle glaucoma underwent yearly DP, VF testing, SD OCT RNFL thickness scans, and optic nerve volume scans (Spectralis; Heidelberg Engineering), all performed on the same day. From high-density optic nerve volume scans, custom-built software calculated the minimum distance band (MDB) thickness, a 3D neuroretinal rim parameter. Patients were classified as glaucoma progressors or nonglaucoma progressors using event-based analysis. Progression by DP and VF testing occurred when 3 masked glaucoma specialists unanimously concurred. Progression by RNFL and MDB thickness occurred if change of more than test-retest variability was observed. Kaplan-Meier curves were constructed to analyze time-to-progression data. Kappa Coefficients were used to measure agreement of progressing eyes among methods. MAIN OUTCOME MEASURES: Time to glaucoma progression among all 4 methods. RESULTS: Global MDB thickness detected glaucoma progression in the highest percentage of eyes (52.4%) compared with DP (16.1%; P < 0.001) and global RNFL thickness (15.3%; P < 0.001). Global MDB thickness detected glaucoma progression earlier than either DP (23 months vs. 44 months; P < 0.001) or global RNFL thickness (23 months vs. 33 months; P < 0.001). Among MDB progressing eyes, 46.2% were confirmed simultaneously or later by other conventional methods. Agreement of glaucoma-progressing eyes for all 4 methods in paired fashion were slight to fair (κ = 0.095-0.300). CONCLUSIONS: High-density 3D SD OCT neuroretinal rim measurements detected glaucoma progression approximately 1 to 2 years earlier compared with current clinically available structural tests (i.e., DP and 2D RNFL thickness measurements).
Raval V, Binkley E, Aronow ME, Valenzuela J, Peereboom DM, Singh AD. Primary central nervous system lymphoma - ocular variant: an interdisciplinary review on management. Surv Ophthalmol 2021;66(6):1009-1020.Abstract
Primary central nervous system lymphoma-ophthalmic variant (PCNSL-O) is an ocular subset of PCNSL predominantly involving subretinal pigment epithelium space, retina, and vitreous. The ophthalmic manifestations can precede, occur simultaneously, or follow other compartments of the CNS. Clinical trials have resulted in a significantly improved outcome in PCNSL patients over the past 2 decades, with a higher proportion of patients receiving frontline high dose methotrexate-based polychemotherapy regimens with curative intent; however, the current management of PCNSL-O remains controversial owing to lack of prospective data. The goals of PCNSL-O treatment are both to achieve local (ocular) control and to prevent tumor-specific mortality from further CNS involvement. Despite achieving high rates of ocular control with intravitreal agents like methotrexate and rituximab, the overall survival is poor, as 65-85% of patients eventually succumb to CNS disease. Few studies define the role of systemic chemotherapy with/without local treatment as a first line induction treatment for PCNSL-O considering limiting factors such as ocular penetration of systemically administered drugs and treatment related neurotoxicity. Also, the role of adjuvant treatment for PCNSL-O to prevent CNS progression and to improve overall survival is unknown. In this systematic review of the literature, we analyze treatment outcomes of various regimens (local, systemic, and combination) in terms of local control, CNS progression, and overall survival.
Reshef ER, Bleier BS, Freitag SK. The Endoscopic Transnasal Approach to Orbital Tumors: A Review. Semin Ophthalmol 2021;36(4):232-240.Abstract
Historically, surgical access to orbital tumors has required a transcutaneous, transconjunctival or transcranial approach. Resection of orbital tumors is notoriously challenging due to the surrounding dense network of critical structures in a confined bony cavity. Advances in endoscopic endonasal surgery, initially used for sinonasal and skull base conditions, have allowed for expansion of its applications beyond the sinorbital interface. In the past decade, the evolution of techniques has enabled a purely endoscopic, minimally invasive approach to medially located orbital pathology with good outcomes. With experience and multidisciplinary collaboration between orbit and rhinologic surgeons, this has expanded to allow for a safe and effective transnasal approach to nearly all regions of the orbit with or without assistance from the orbital side. This review summarizes the relevant anatomy, variations of surgical approaches, and literature regarding outcomes of the endoscopic endonasal approach to orbital tumors.
Rodríguez-Valdés PJ, Rehak M, Zur D, Sala-Puigdollers A, Fraser-Bell S, Lupidi M, Chhablani J, Cebeci Z, Laíns I, Chaikitmongkol V, Fung AT, Okada M, Unterlauft JD, Smadar L, Loewenstein A, Iglicki M, Busch C. GRAding of functional and anatomical response to DExamethasone implant in patients with Diabetic Macular Edema: GRADE-DME Study. Sci Rep 2021;11(1):4738.Abstract
To analyze functional and anatomical response patterns to dexamethasone (DEX) implant in diabetic macular edema (DME), to describe proportion of responders and non-responders, and to propose a new DME grading system. Retrospective, multicenter, observational cohort study. Naïve and non-naïve DME patients were treated with DEX, with visual acuity (VA) ≥ 0.2 logMAR and central subfield thickness (CST) of ≥ 300 µm. Functional and anatomical responses were graded after 2 and 4 months, and categorized as early and stable improvement, early and progressive improvement, pendular response, delayed improvement, and persistent non-response. 417 eyes were included (175 treatment naïve eyes). Compared to non-naïve eyes, naïve eyes showed a very good functional response (VA gain ≥ 10 letters) more frequently after 2 and 4 months (56% and 57% [naïve] vs. 33% and 28% [non-naïve], p < 0.001). A VA gain < 5 letters (non-response) after 2 and 4 months was seen in 18% and 16% of naïve eyes, and in 49% and 53% of non-naïve eyes (p < 0.001). A lack of anatomical response was rare in both groups, but more frequently in non-naïve eyes (12% vs. 4%, p = 0.003). Functionally and anatomically, naïve eyes showed most frequently an early and stable improvement (functionally: 77/175 44%; anatomically: 123/175 eyes, 70%). Most non-naïve eyes experienced no significant improvement functionally (97/242 eyes, 40%), despite a mostly early and stable improvement anatomical response pattern (102/242 eyes, 42%). Functional but not anatomical response patterns were influenced by baseline VA. Naïve and non-naïve eyes show different functional and anatomical response patterns to DEX implant. Functional non-responders are rare in naïve eyes, whereas anatomical non-response is unusual in both groups.
Roldan AM, Zebardast N, Pistilli M, Khachatryan N, Payal A, Begum H, Artornsombudh P, Pujari SS, Rosenbaum JT, Sen NH, Suhler EB, Thorne JE, Bhatt NP, Foster SC, Jabs DA, Levy-Clarke GA, Nussenblatt RB, Buchanich JM, Kempen JH, for Group SITED (SITE) CSR. Corneal Endothelial Transplantation in Uveitis: Incidence and Risk Factors. Am J Ophthalmol 2021;Abstract
PURPOSE: To estimate the incidence of corneal endothelial transplantation and identify risk factors among patients with non-infectious ocular inflammation. DESIGN: Retrospective cohort study. METHODS: Adult patients attending United States tertiary uveitis care facilities diagnosed with non-infectious ocular inflammation were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Time-to-event analysis was used to estimate the incidence of corneal endothelial transplantation (CET), including penetrating keratoplasty, Descemet stripping endothelial keratoplasty, or Descemet Membrane Endothelial Keratoplasty procedures. The incidence of CET was calculated; potential risk factors for CET were also evaluated using Cox regression, accounting for correlation between eyes of the same patient. RESULTS: Overall, 14,264 eyes met eligibility criteria for this analysis with a median follow-up 1.8 eye-years. The Kaplan-Meier estimated incidence of CET within 10 years was 1.10% (95% CI, 0.68%-1.53%). Risk factors for CET included age >60 years vs. <40 years (aHR 16.5; 95% CI,4.70-57.9), anterior uveitis and scleritis vs. other types (aHR 2.97; 95% CI, 1.46-6.05 and aHR 4.14; 95% CI,1.28-13.4, respectively), topical corticosteroid treatment (aHR 2.84; 95% CI, 1.32-6.13), cataract surgery (aHR 4.44; 95% CI, 1.73-11.4), tube shunt surgery (aHR 11.9; 95% CI, 5.30-26.8), band keratopathy (aHR 5.12; 95% CI, 2.34-11.2), and hypotony (aHR 7.38; 95% CI, 3.14-17.4). Duration of uveitis, trabeculectomy, PAS, and ocular hypertension had no significant association after multivariate adjustment. CONCLUSIONS: In patients with ocular inflammation, CET occurred infrequently. Tube shunt surgery, hypotony, band keratopathy, cataract surgery, and anterior segment inflammation were associated with increased risk of undergoing corneal endothelial transplantation; these factors likely are associated with endothelial cell damage.
Rosenblatt TR, Vail D, Ludwig CA, Al-Moujahed A, Pasricha MV, Ji MH, Callaway NF, Moshfeghi DM. Fall risk in patients with pseudophakic monovision. Can J Ophthalmol 2021;Abstract
OBJECTIVE: Vision changes can precipitate falls in the elderly resulting in significant morbidity and mortality. We hypothesized that pseudophakic monovision and ensuing anisometropia and aniseikonia impact elderly fall risk. This study assessed fall risk in patients with pseudophakic monovision, pseudophakic single vision distance (classic cataract surgery), and cataracts with no surgery. DESIGN: Retrospective single-institution cohort study PARTICIPANTS: Patients with bilateral cataracts diagnosed at 60 years of age or older who underwent bilateral cataract surgery (monovision or single vision distance) or did not undergo any cataract surgery (n = 13 385). Patients with unilateral surgery or a fall prior to cataract diagnosis were excluded. METHODS: Data were obtained from the Stanford Research Repository. Time-to-fall analysis was performed across all 3 groups. Primary outcome was hazard ratio (HR) for fall after second eye cataract surgery or after bilateral cataract diagnosis. RESULTS: Of 13 385 patients (241 pseudophakic monovision, 2809 pseudophakic single vision, 10 335 no surgery), 850 fell after cataract diagnosis. Pseudophakic monovision was not associated with fall risk after controlling for age, sex, and myopia. Pseudophakic single-vision patients had a decreased time to fall compared with no-surgery patients (log rank, p < 0.001). Older age at cataract diagnosis (HR =1.05, 95% confidence interval [CI] 1.04-1.06, p < 0.001) or at time of surgery (HR = 1.05, 95% CI 1.03-1.07, p < 0.001) increased fall risk, as did female sex (HR = 1.29, 95% CI 1.10-1.51, p = 0.002) and preexisting myopia (HR = 1.31, 95% CI 1.01-1.71, p = 0.046) among nonsurgical patients. CONCLUSIONS: Pseudophakic monovision did not impact fall risk, but pseudophakic single vision may increase falls compared with patients without cataract surgery.
Rosenblatt TR, Ji MH, Vail D, Ludwig CA, Al-Moujahed A, Pasricha MV, Callaway NF, Kumm J, Moshfeghi DM. Key factors in a rigorous longitudinal image-based assessment of retinopathy of prematurity. Sci Rep 2021;11(1):5369.Abstract
To describe a database of longitudinally graded telemedicine retinal images to be used as a comparator for future studies assessing grader recall bias and ability to detect typical progression (e.g. International Classification of Retinopathy of Prematurity (ICROP) stages) as well as incremental changes in retinopathy of prematurity (ROP). Cohort comprised of retinal images from 84 eyes of 42 patients who were sequentially screened for ROP over 6 consecutive weeks in a telemedicine program and then followed to vascular maturation or treatment, and then disease stabilization. De-identified retinal images across the 6 weekly exams (2520 total images) were graded by an ROP expert based on whether ROP had improved, worsened, or stayed the same compared to the prior week's images, corresponding to an overall clinical "gestalt" score. Subsequently, we examined which parameters might have influenced the examiner's ability to detect longitudinal change; images were graded by the same ROP expert by image view (central, inferior, nasal, superior, temporal) and by retinal components (vascular tortuosity, vascular dilation, stage, hemorrhage, vessel growth), again determining if each particular retinal component or ROP in each image view had improved, worsened, or stayed the same compared to the prior week's images. Agreement between gestalt scores and view, component, and component by view scores was assessed using percent agreement, absolute agreement, and Cohen's weighted kappa statistic to determine if any of the hypothesized image features correlated with the ability to predict ROP disease trajectory in patients. The central view showed substantial agreement with gestalt scores (κ = 0.63), with moderate agreement in the remaining views. Of retinal components, vascular tortuosity showed the most overall agreement with gestalt (κ = 0.42-0.61), with only slight to fair agreement for all other components. This is a well-defined ROP database graded by one expert in a real-world setting in a masked fashion that correlated with the actual (remote in time) exams and known outcomes. This provides a foundation for subsequent study of telemedicine's ability to longitudinally assess ROP disease trajectory, as well as for potential artificial intelligence approaches to retinal image grading, in order to expand patient access to timely, accurate ROP screening.
Rossin EJ, Gilbert AL, Koen N, Leslie-Mazwi TM, Cunnane ME, Rizzo JF. Site of Origin of the Ophthalmic Artery Influences the Risk for Retinal Versus Cerebral Embolic Events. J Neuroophthalmol 2021;41(1):24-28.Abstract
BACKGROUND: Embolic events leading to retinal ischemia or cerebral ischemia share common risk factors; however, it has been well documented that the rate of concurrent cerebral infarction is higher in patients with a history of transient ischemic attack (TIA) than in those with monocular vision loss (MVL) due to retinal ischemia. Despite the fact that emboli to the ophthalmic artery (OA) and middle cerebral artery share the internal carotid artery (ICA) as a common origin or transit for emboli, the asymmetry in their final destination has not been fully explained. We hypothesize that the anatomic location of the OA takeoff from the ICA may contribute to the differential flow of small emboli to the retinal circulation vs the cerebral circulation. METHODS: We report a retrospective, comparative, case-control study on 28 patients with retinal ischemia and 26 patients with TIA or cerebral infarction caused by embolic events. All subjects underwent either computed tomography angiography or MRA. The location of the ipsilateral OA origin off the ICA was then graded in a blinded fashion and compared between cohorts. Vascular risk factors were collected for all patients, including age, sex, hypertension, hyperlipidemia, arrhythmia, diabetes, coronary artery disease, and smoking. RESULTS: We find that in patients with retinal ischemia of embolic etiology, the ipsilateral OA takeoff from the ICA is more proximal than in patients with cerebral infarcts or TIA (P = 0.0002). We found no statistically significant differences in demographic, vascular, or systemic risk factors. CONCLUSIONS: We find that the mean anatomical location of the OA takeoff from the ICA is significantly more proximal in patients with MVL due to retinal ischemia compared with patients with TIA or cerebral ischemia. This finding contributes significantly to our understanding of a long observed but poorly understood phenomenon that patients with MVL are less likely to have concurrent cerebral ischemia than are patients with TIA.
Rossin EJ, Tsui I, Wong SC, Hou KK, Prakhunhungsit S, Blair MP, Shapiro MJ, Leishman L, Nagiel A, Lifton JA, Quiram P, Ringeisen AL, Henderson RH, Arruti N, Buzzacco DM, Kusaka S, Ferrone PJ, Belin PJ, Chang E, Hubschman J-P, Murray TG, Leung EH, Wu W-C, Olsen KR, Harper AC, Rahmani S, Goldstein J, Lee T, Nudleman E, Cernichiaro-Espinosa LA, Chhablani J, Berrocal AM, Yonekawa Y. Traumatic Retinal Detachment in Patients with Self-Injurious Behavior: An International Multicenter Study. Ophthalmol Retina 2021;5(8):805-814.Abstract
PURPOSE: To describe the clinical characteristics, surgical outcomes, and management recommendations in patients with traumatic rhegmatogenous retinal detachment (RRD) resulting from self-injurious behavior (SIB). DESIGN: International, multicenter, retrospective, interventional case series. PARTICIPANTS: Patients with SIB from 23 centers with RRD in at least 1 eye. METHODS: Clinical histories, preoperative assessment, surgical details, postoperative management, behavioral intervention, and follow-up examination findings were reviewed. MAIN OUTCOME MEASURES: The rate of single-surgery anatomic success (SSAS) was the primary outcome. Other outcomes included new RRD in formerly attached eyes, final retinal reattachment, and final visual acuity. RESULTS: One hundred seven eyes with RRDs were included from 78 patients. Fifty-four percent of patients had bilateral RRD or phthisis bulbi in the fellow eye at final follow-up. The most common systemic diagnoses were autism spectrum disorder (35.9%) and trisomy 21 (21.8%) and the most common behavior was face hitting (74.4%). The average follow-up time was 3.3 ± 2.8 years, and surgical outcomes for operable eyes were restricted to patients with at least 3 months of follow-up (81 eyes). Primary initial surgeries were vitrectomy alone (33.3%), primary scleral buckle (SB; 26.9%), and vitrectomy with SB (39.7%), and 5 prophylactic SBs were placed. Twenty-three eyes (21.5%) with RRDs were inoperable. The SSAS was 23.1% without tamponade (37.2% if including silicone oil), and final reattachment was attained in 80% (36.3% without silicone oil tamponade). Funnel-configured RRD (P = 0.006) and the presence of grade C proliferative vitreoretinopathy (P = 0.002) correlated with re-detachment. The use of an SB predicted the final attachment rate during the initial surgery (P = 0.005) or at any surgery (P = 0.008. These associations held if restricting to 64 patients with ≥12 months followup. Anatomic reattachment correlated with better visual acuity (P < 0.001). CONCLUSIONS: RRD resulting from SIB poses therapeutic challenges because of limited patient cooperation, bilateral involvement, chronicity, and ongoing trauma in vulnerable and neglected patients. The surgical success rates were some of the lowest in the modern retinal detachment literature. The use of an SB may result in better outcomes, and visual function can be restored in some patients.
Rossin EJ, Sobrin L, Kim LA. Single-cell RNA sequencing: An overview for the ophthalmologist. Semin Ophthalmol 2021;36(4):191-197.Abstract
Understanding the molecular composition of pathogenic tissues is a critical step in understanding the pathophysiology of disease and designing therapeutics. First described in 2009, single cell RNA sequencing (scRNAseq) is a methodology whereby thousands of cells are simultaneously isolated into individual micro-environments that can be altered experimentally and the genome-wide RNA expression of each cell is captured. It has undergone significant technological improvement over the last decade and gained tremendous popularity. scRNAseq is an improvement over prior pooled RNA analyses which cannot identify the cellular composition and heterogeneity of a tissue of interest. This new approach offers new opportunity for new discovery, as tissue samples can now be sub-categorized into groups of cell types based on genome-wide gene expression in an unbiased fashion. As ophthalmologists, we are uniquely positioned to obtain pathologic samples from the eye for further study. ScRNAseq has already been applied in ophthalmology to characterize retinal tissue, and it may offer the key to understanding various pathological processes in the future.
Rossin EJ, Szypko C, Giese I, Hall N, Gardiner MF, Lorch A. Factors Associated With Increased Risk of Serious Ocular Injury in the Setting of Orbital Fracture. JAMA Ophthalmol 2021;139(1):77-83.Abstract
Importance: Orbital fractures are common in ocular trauma, and there is a need to develop predictive tools to estimate risk of concurrent ocular injury. Objective: To identify clinical and radiographic features that are associated with increased risk of substantial ocular injury in the setting of orbital fracture. Design, Setting, and Participants: Retrospective consecutive case series of patients who sustained orbital fractures between 2012 and 2018. Examinations were done at 1 of 2 level 1 trauma centers in the emergency or inpatient setting. A total of 430 consecutive patients (500 eyes) between 2012 and 2017 met inclusion criteria for the training sample. After building a predictive model, 88 additional consecutive patients (97 eyes) between 2017 and 2018 who met inclusion criteria were collected as a test sample. Main Outcomes and Measures: The primary outcome measure was substantial ocular injury distinct from orbital fracture. Results: The mean age of our patient population was 53.5 years (range, 16-100 years). The overall rate of substantial ocular injury was 20.4%, and the rate of injury requiring immediate ophthalmic attention was 14.4%. Five variables were found to be associated with increased risk of substantial ocular injury: blunt trauma with a foreign object (odds ratio [OR], 19.4; 95% CI, 6.3-64.1; P < .001), inability to count fingers (OR, 10.1; 95% CI, 2.8-41.1; P = .002), roof fracture (OR, 9.1; 95% CI, 2.8-30.0; P = .002), diplopia on primary gaze (OR, 6.7; 95% CI, 1.7-25.1; P = .003), and conjunctival hemorrhage or chemosis (OR, 4.2; 95% CI, 2.2-8.5; P < .001). The results were translated into a bedside tool that was tested in an independent group of eyes (n = 97) and found to be associated with substantial ocular injury with a 95% sensitivity (95% CI, 77.2-99.9), 40% specificity (95% CI, 28.9-52.0), 31.8% positive predictive value (95% CI, 27.5-36.5), and 96.8% negative predictive value (95% CI, 81.3-99.5). Conclusions and Relevance: A minority of patients with an orbital fracture had a substantial ocular injury. Certain radiographic and clinical findings were associated with substantial ocular injury. Testing of the algorithm in prospective longitudinal settings appears warranted.
Rothman AL, Chang R, Kolomeyer NN, Turalba A, Stein JD, Boland MV. American Glaucoma Society Position Paper: Information Sharing Using Established Standards is Essential to the Future of Glaucoma Care. Ophthalmol Glaucoma 2021;
Ruan Y, Jiang S, Musayeva A, Pfeiffer N, Gericke A. Corneal Epithelial Stem Cells-Physiology, Pathophysiology and Therapeutic Options. Cells 2021;10(9)Abstract
In the human cornea, regeneration of the epithelium is regulated by the stem cell reservoir of the limbus, which is the marginal region of the cornea representing the anatomical and functional border between the corneal and conjunctival epithelium. In support of this concept, extensive limbal damage, e.g., by chemical or thermal injury, inflammation, or surgery, may induce limbal stem cell deficiency (LSCD) leading to vascularization and opacification of the cornea and eventually vision loss. These acquired forms of limbal stem cell deficiency may occur uni- or bilaterally, which is important for the choice of treatment. Moreover, a variety of inherited diseases, such as congenital aniridia or dyskeratosis congenita, are characterized by LSCD typically occurring bilaterally. Several techniques of autologous and allogenic stem cell transplantation have been established. The limbus can be restored by transplantation of whole limbal grafts, small limbal biopsies or by ex vivo-expanded limbal cells. In this review, the physiology of the corneal epithelium, the pathophysiology of LSCD, and the therapeutic options will be presented.
Rubinfeld RS, Gum GG, Talamo JH, Parsons EC. The Effect of Sodium Iodide on Stromal Loading, Distribution and Degradation of Riboflavin in a Rabbit Model of Transepithelial Corneal Crosslinking. Clin Ophthalmol 2021;15:1985-1994.Abstract
Purpose: To evaluate effects of sodium iodide (NaI) on riboflavin concentration in corneal stroma before and during ultraviolet A (UVA) light exposure using a novel transepithelial corneal collagen crosslinking (CXL) procedure (EpiSmart CXL system, CXL Ophthalmics, Encinitas CA). Methods: Riboflavin solutions with NaI (Ribostat, CXL Ophthalmics, Encinitas CA) and without NaI were used for CXL in rabbits using EpiSmart. A pilot study determined sufficient riboflavin loading time. Four rabbits were dosed and monitored. Riboflavin fluorescence intensity was assessed from masked slit-lamp photos. A 12 min loading time was selected. Sixteen additional rabbits received the two formulae in contralateral eyes for CXL. Riboflavin uptake was assessed at 0, 10, 15, 20, 25, and 30 min of UVA exposure using a scale for riboflavin fluorescence previously validated against stromal concentration. Post sacrifice, corneal stromal samples were analyzed for concentrations of riboflavin and riboflavin 5'-phosphate. Results: Eyes dosed with NaI riboflavin had higher riboflavin grades compared to eyes dosed with the NaI-free riboflavin formulation immediately after riboflavin loading and persisting throughout UVA exposure, with significantly higher (P < 0.01 to < 0.05) riboflavin grades from 15 through 25 min of UVA exposure. Riboflavin grades decreased more slowly in eyes dosed with NaI riboflavin through 25 minutes of UVA exposure. Minor conjunctival irritation was noted with or without NaI. Conclusion: The addition of NaI to riboflavin solution is associated with increased riboflavin concentration in corneal stroma throughout a clinically relevant time course of UVA exposure. This effect may be a combination of enhanced epithelial penetration and reduced riboflavin photodegradation and should enhance intrastromal crosslinking.
Ruiz-Lozano RE, Garza-Garza LA, Davila-Cavazos O, Foster SC, Rodriguez-Garcia A. The clinical and pathogenic spectrum of surgically-induced scleral necrosis: A review. Surv Ophthalmol 2021;66(4):594-611.Abstract
The onset of scleral necrosis after ocular surgery may have catastrophic ocular and systemic consequences. The two most frequent surgeries causing surgically-induced scleral necrosis (SISN) are pterygium excision and cataract extraction. Several pathogenic mechanisms are involved in surgically induced scleral necrosis. All of them are poorly understood. Ocular trauma increasing lytic action of collagenases with subsequent collagen degradation, vascular disruption leading to local ischemia, and immune complex deposition activating the complement system represents some of the events that lead to scleral necrosis. The complex cascade of events involving different pathogenic mechanisms and the patient's abnormal immune response frequently leads to delayed wound healing that predisposes the development of scleral necrosis. The management of SISN ranges from short-term systemic anti-inflammatory drugs to aggressive immunosuppressive therapy and surgical repair. Therefore, before performing any ocular surgery involving the sclera, a thorough ophthalmic and systemic evaluation must be done to identify high-risk patients that may develop SISN.
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Saddala MS, Lennikov A, Mukwaya A, Yang X, Tang S, Huang H. Data mining and network analysis reveals C-X-C chemokine receptor type 5 is involved in the pathophysiology of age-related macular degeneration. J Biomol Struct Dyn 2021;:1-10.Abstract
Our previous studies found that the C-X-C motif chemokine receptor 5 (CXCR5) loss leads to retinal pigment epithelium (RPE) dysfunction and AMD pathogenesis. The current study aimed to characterize the G protein-coupled receptor (GPCR) structure of CXCR5 and analyze its interactions with AMD-related risk genes. The sequence alignments, homology model of CXCR5 and structural assessment analysis were performed. Data and text mining were then performed to identify AMD-related risk genes and their interaction with CXCR5 using statistical and mathematical algorithms. Sequence alignment and phylogenetic tree analysis revealed that human CXCR5 was highly similar (85.4839%) to the rabbit. The least similarity (33.871%) was found to be in zebrafish compared to the other species. The CXCR5 model structural assessment and secondary structure analysis exhibited an excellent model. Network analysis revealed that IL10, TNF, ICAM1, CXCL1, CXCL8, APP, TLR4, SELL, C3, IL17A and CCR2 were the most connected genes CXCR5. These findings suggest that CXCR5 signaling may regulate the biological function of RPE and modulate AMD pathophysiology via GPCR signaling and interacting with identified AMD risk genes. In summary, the data presented here provide novel and crucial insights into the molecular mechanisms of CXCR5 involvement in AMD.Communicated by Ramaswamy H. Sarma.
Saeedi O, Boland MV, D'Acunto L, Swamy R, Hegde V, Gupta S, Venjara A, Tsai J, Myers JS, Wellik SR, DeMoraes G, Pasquale LR, Shen LQ, Li Y, Elze T. Development and Comparison of Machine Learning Algorithms to Determine Visual Field Progression. Transl Vis Sci Technol 2021;10(7):27.Abstract
Purpose: To develop and test machine learning classifiers (MLCs) for determining visual field progression. Methods: In total, 90,713 visual fields from 13,156 eyes were included. Six different progression algorithms (linear regression of mean deviation, linear regression of the visual field index, Advanced Glaucoma Intervention Study algorithm, Collaborative Initial Glaucoma Treatment Study algorithm, pointwise linear regression [PLR], and permutation of PLR) were applied to classify each eye as progressing or stable. Six MLCs were applied (logistic regression, random forest, extreme gradient boosting, support vector classifier, convolutional neural network, fully connected neural network) using a training and testing set. For MLC input, visual fields for a given eye were divided into the first and second half and each location averaged over time within each half. Each algorithm was tested for accuracy, sensitivity, positive predictive value, and class bias with a subset of visual fields labeled by a panel of three experts from 161 eyes. Results: MLCs had similar performance metrics as some of the conventional algorithms and ranged from 87% to 91% accurate with sensitivity ranging from 0.83 to 0.88 and specificity from 0.92 to 0.96. All conventional algorithms showed significant class bias, meaning each individual algorithm was more likely to grade uncertain cases as either progressing or stable (P ≤ 0.01). Conversely, all MLCs were balanced, meaning they were equally likely to grade uncertain cases as either progressing or stable (P ≥ 0.08). Conclusions: MLCs showed a moderate to high level of accuracy, sensitivity, and specificity and were more balanced than conventional algorithms. Translational Relevance: MLCs may help to determine visual field progression.

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