2021

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Shuldiner SR, Boland MV, Ramulu PY, De Moraes GC, Elze T, Myers J, Pasquale L, Wellik S, Yohannan J. Predicting eyes at risk for rapid glaucoma progression based on an initial visual field test using machine learning. PLoS One 2021;16(4):e0249856.Abstract
OBJECTIVE: To assess whether machine learning algorithms (MLA) can predict eyes that will undergo rapid glaucoma progression based on an initial visual field (VF) test. DESIGN: Retrospective analysis of longitudinal data. SUBJECTS: 175,786 VFs (22,925 initial VFs) from 14,217 patients who completed ≥5 reliable VFs at academic glaucoma centers were included. METHODS: Summary measures and reliability metrics from the initial VF and age were used to train MLA designed to predict the likelihood of rapid progression. Additionally, the neural network model was trained with point-wise threshold data in addition to summary measures, reliability metrics and age. 80% of eyes were used for a training set and 20% were used as a test set. MLA test set performance was assessed using the area under the receiver operating curve (AUC). Performance of models trained on initial VF data alone was compared to performance of models trained on data from the first two VFs. MAIN OUTCOME MEASURES: Accuracy in predicting future rapid progression defined as MD worsening more than 1 dB/year. RESULTS: 1,968 eyes (8.6%) underwent rapid progression. The support vector machine model (AUC 0.72 [95% CI 0.70-0.75]) most accurately predicted rapid progression when trained on initial VF data. Artificial neural network, random forest, logistic regression and naïve Bayes classifiers produced AUC of 0.72, 0.70, 0.69, 0.68 respectively. Models trained on data from the first two VFs performed no better than top models trained on the initial VF alone. Based on the odds ratio (OR) from logistic regression and variable importance plots from the random forest model, older age (OR: 1.41 per 10 year increment [95% CI: 1.34 to 1.08]) and higher pattern standard deviation (OR: 1.31 per 5-dB increment [95% CI: 1.18 to 1.46]) were the variables in the initial VF most strongly associated with rapid progression. CONCLUSIONS: MLA can be used to predict eyes at risk for rapid progression with modest accuracy based on an initial VF test. Incorporating additional clinical data to the current model may offer opportunities to predict patients most likely to rapidly progress with even greater accuracy.
Siddiqui N, Chen EM, Parikh R, Douglas VP, Douglas KA, Feng PW, Armstrong GW. Epidemiology of United States Inpatient Open Globe Injuries from 2009-2015. Ophthalmic Epidemiol 2021;28(6):469-478.Abstract
PURPOSE: To study the epidemiology of inpatient open globe injuries (OGI) in the United States (US). METHODS: This was a retrospective cohort study of patients with a primary diagnosis of OGI in the National Inpatient Sample (NIS) from 2009 to 2015. Sociodemographic characteristics, including age, gender, race, ethnicity, insurance, and income were stratified for comparison. Annual prevalence rates were calculated using 2010 US Census data. Statistical analysis included Chi-square tests, ANCOVA, and Tukey tests. RESULTS: A total of 6,821 US inpatient hospital discharge records met inclusion/exclusion criteria. The estimated national prevalence of OGI during the 5-year period from 2009 to 2015 was 34,061 (95% confidence interval [CI] 31,445-36,677). The overall annual prevalence rate was 1.58 per 100,000 per year (CI 1.56-1.59). Overall, average annual prevalence rates were highest among patients 85 years or older (7.72, CI 6.95-8.49), on Medicare (3.92, CI 3.84-4.00), males (2.28, CI 2.25-2.30), African Americans (2.38, CI 2.32-2.44), and Native Americans (1.80, CI 1.62-2.00). OGI rates were lowest among Whites (1.21, CI 1.19-1.22), females (0.89, CI 0.87-0.91), those with private insurance (0.84, CI 0.82-0.86), and Asians (0.69, CI 0.64-0.74). Being in the lowest income quartile was a risk factor for OGI (p < .05). CONCLUSIONS: Inpatient OGIs disproportionately affected those over 85, young males, elderly females, patients of African-American descent, on Medicare, and in the lowest income quartile. Additionally, children and young children had lower rates of OGI compared to adolescents. Further studies should delineate causes for socioeconomic differences in OGI rates to guide future public health measures.
Silpa-Archa S, Ittharat W, Chotcomwongse P, Preble JM, Foster SC. Analysis of Three-Dimensional Choroidal Volume with Enhanced Depth Imaging Findings in Patients with Recurrent Vogt-Koyanagi-Harada Disease. Curr Eye Res 2021;46(7):1010-1017.Abstract
Purpose: To demonstrate changes in three-dimensional choroidal volume with enhanced depth imaging optical coherence tomography (EDI-OCT) in patients with recurrent stage of Vogt-Koyanagi-Harada disease (VKH).Materials and Methods: This prospective comparative case series included 9 patients with recurrent VKH, 10 patients with quiet VKH, and 15 healthy controls after sample size was calculated. All VKH cases with recurrences underwent raster scanning with EDI-OCT at active and inactive stages of the disease.Results: All choroidal parameters in the active stage significantly reduced when the inflammation subsided: total choroidal volume (P = .02), central choroidal volume (P = .01), central choroidal thickness (P = .03). The changes in central choroidal volume over the resolution phase were more pronounced than the changes in central choroidal thickness in 56% of cases. Two cases presenting with only subclinical posterior segment recurrence had their choroidal parameters recovered after prompt treatment.Conclusions: In the recurrent stage of VKH, alteration in choroidal volume was evident by EDI-OCT even in an absence of anterior segment inflammation. Central choroidal volume may serve as a biomarker for detecting choroidal morphological change.
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.
Simpson FC, McTiernan CD, Islam MM, Buznyk O, Lewis PN, Meek KM, Haagdorens M, Audiger C, Lesage S, Gueriot F-X, Brunette I, Robert M-C, Olsen D, Koivusalo L, Liszka A, Fagerholm P, Gonzalez-Andrades M, Griffith M. Collagen analogs with phosphorylcholine are inflammation-suppressing scaffolds for corneal regeneration from alkali burns in mini-pigs. Commun Biol 2021;4(1):608.Abstract
The long-term survival of biomaterial implants is often hampered by surgery-induced inflammation that can lead to graft failure. Considering that most corneas receiving grafts are either pathological or inflamed before implantation, the risk of rejection is heightened. Here, we show that bioengineered, fully synthetic, and robust corneal implants can be manufactured from a collagen analog (collagen-like peptide-polyethylene glycol hybrid, CLP-PEG) and inflammation-suppressing polymeric 2-methacryloyloxyethyl phosphorylcholine (MPC) when stabilized with the triazine-based crosslinker 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride. The resulting CLP-PEG-MPC implants led to reduced corneal swelling, haze, and neovascularization in comparison to CLP-PEG only implants when grafted into a mini-pig cornea alkali burn model of inflammation over 12 months. Implants incorporating MPC allowed for faster nerve regeneration and recovery of corneal sensation. CLP-PEG-MPC implants appear to be at a more advanced stage of regeneration than the CLP-PEG only implants, as evidenced by the presence of higher amounts of cornea-specific type V collagen, and a corresponding decrease in the presence of extracellular vesicles and exosomes in the corneal stroma, in keeping with the amounts present in healthy, unoperated corneas.
Singh RB, Liu L, Yung A, Anchouche S, Mittal SK, Blanco T, Dohlman TH, Yin J, Dana R. Ocular redness - II: Progress in development of therapeutics for the management of conjunctival hyperemia. Ocul Surf 2021;21:66-77.Abstract
Conjunctival hyperemia is one of the most common causes for visits to primary care physicians, optometrists, ophthalmologists, and emergency rooms. Despite its high incidence, the treatment options for patients with conjunctival hyperemia are restricted to over-the-counter drugs that provide symptomatic relief due to short duration of action, tachyphylaxis and rebound redness. As our understanding of the immunopathological pathways causing conjunctival hyperemia expands, newer therapeutic targets are being discovered. These insights have also contributed to the development of animal models for mimicking the pathogenic changes in microvasculature causing hyperemia. Furthermore, this progress has catalyzed the development of novel therapeutics that provide efficacious, long-term relief from conjunctival hyperemia with minimal adverse effects.
Singh RB, Blanco T, Mittal SK, Alemi H, Chauhan SK, Chen Y, Dana R. Pigment Epithelium-Derived Factor Enhances the Suppressive Phenotype of Regulatory T Cells in a Murine Model of Dry Eye Disease. Am J Pathol 2021;191(4):720-729.Abstract
Pigment epithelium-derived factor (PEDF) is a widely expressed 50-kDa glycoprotein belonging to the serine protease inhibitor family, with well-established anti-inflammatory functions. Recently, we demonstrated the immunoregulatory role played by PEDF in dry eye disease (DED) by suppressing the maturation of antigen-presenting cells at the ocular surface following exposure to the desiccating stress. In this study, we evaluated the effect of PEDF on the immunosuppressive characteristics of regulatory T cells (Tregs), which are functionally impaired in DED. In the presence of PEDF, the in vitro cultures prevented proinflammatory cytokine (associated with type 17 helper T cells)-induced loss of frequency and suppressive phenotype of Tregs derived from normal mice. Similarly, PEDF maintained the in vitro frequency and enhanced the suppressive phenotype of Tregs derived from DED mice. On systemically treating DED mice with PEDF, moderately higher frequencies and significantly enhanced suppressive function of Tregs were observed in the draining lymphoid tissues, leading to the efficacious amelioration of the disease. Our results demonstrate that PEDF promotes the suppressive capability of Tregs and attenuates their type 17 helper T-cell-mediated dysfunction in DED, thereby playing a role in the suppression of DED.
Singh RB, Gupta P, Kartik A, Farooqui N, Singhal S, Shergill S, Singh KP, Agarwal A. Ocular Manifestations of Neuronal Ceroid Lipofuscinoses. Semin Ophthalmol 2021;36(7):582-595.Abstract
Neuronal ceroid lipofuscinoses (NCLs) are a group of rare neurodegenerative storage disorders associated with devastating visual prognosis, with an incidence of 1/1,000,000 in the United States and comparatively higher incidence in European countries. The pathophysiological mechanisms causing NCLs occur due to enzymatic or transmembrane defects in various sub-cellular organelles including lysosomes, endoplasmic reticulum, and cytoplasmic vesicles. NCLs are categorized into different types depending upon the underlying cause i.e., soluble lysosomal enzyme deficiencies or non-enzymatic deficiencies (functions of identified proteins), which are sub-divided based on an axial classification system. In this review, we have evaluated the current evidence in the literature and reported the incidence rates, underlying mechanisms and currently available management protocols for these rare set of neuroophthalmological disorders. Additionally, we also highlighted the potential therapies under development that can expand the treatment of these rare disorders beyond symptomatic relief.
Singh RB, Das S, Chodosh J, Sharma N, Zegans ME, Kowalski RP, Jhanji V. Paradox of complex diversity: Challenges in the diagnosis and management of bacterial keratitis. Prog Retin Eye Res 2021;:101028.Abstract
Bacterial keratitis continues to be one of the leading causes of corneal blindness in the developed as well as the developing world, despite swift progress since the dawn of the "anti-biotic era". Although, we are expeditiously developing our understanding about the different causative organisms and associated pathology leading to keratitis, extensive gaps in knowledge continue to dampen the efforts for early and accurate diagnosis, and management in these patients, resulting in poor clinical outcomes. The ability of the causative bacteria to subdue the therapeutic challenge stems from their large genome encoding complex regulatory networks, variety of unique virulence factors, and rapid secretion of tissue damaging proteases and toxins. In this review article, we have provided an overview of the established classical diagnostic techniques and therapeutics for keratitis caused by various bacteria. We have extensively reported our recent in-roads through novel tools for accurate diagnosis of mono- and poly-bacterial corneal infections. Furthermore, we outlined the recent progress by our group and others in understanding the sub-cellular genomic changes that lead to antibiotic resistance in these organisms. Finally, we discussed in detail, the novel therapies and drug delivery systems in development for the efficacious management of bacterial keratitis.
Singh RB, Liu L, Anchouche S, Yung A, Mittal SK, Blanco T, Dohlman TH, Yin J, Dana R. Ocular redness - I: Etiology, pathogenesis, and assessment of conjunctival hyperemia. Ocul Surf 2021;21:134-144.Abstract
The translucent appearance of the conjunctiva allows for immediate visualization of changes in the circulation of the conjunctival microvasculature consisting of extensive branching of superficial and deep arterial systems and corresponding drainage pathways, and the translucent appearance of the conjunctiva allows for immediate visualization of changes in the circulation. Conjunctival hyperemia is caused by a pathological vasodilatory response of the microvasculature in response to inflammation due to a myriad of infectious and non-infectious etiologies. It is one of the most common contributors of ocular complaints that prompts visits to medical centers. Our understanding of these neurogenic and immune-mediated pathways has progressed over time and has played a critical role in developing targeted novel therapies. Due to a multitude of underlying etiologies, patients must be accurately diagnosed for efficacious management of conjunctival hyperemia. The diagnostic techniques used for the grading of conjunctival hyperemia have also evolved from descriptive and subjective grading scales to more reliable computer-based objective grading scales.
Singh RB, Khera T, Ly V, Saini C, Cho W, Shergill S, Singh KP, Agarwal A. Ocular complications of perioperative anesthesia: a review. Graefes Arch Clin Exp Ophthalmol 2021;259(8):2069-2083.Abstract
Ocular complications associated with anesthesia in ocular and non-ocular surgeries are rare adverse events which may present with clinical presentations vacillating between easily treatable corneal abrasions to more serious complication such as irreversible bilateral vision loss. In this review, we outline the different techniques of anesthetic delivery in ocular surgeries and highlight the incidence and etiologies of associated injuries. The changes in vision in non-ocular surgeries are mistaken for residual sedation or anesthetics, therefore require high clinical suspicion on part of the treating ophthalmologists, to ensure early diagnosis, adequate and swift management especially in surgeries such as cardiac, spine, head and neck, and some orthopedic procedures, that have a comparatively higher incidence of ocular complications. In this article, we review the literature for reports on the clinical incidence of different ocular complications associated with anesthesia in non-ocular surgeries and outline the current understanding of pathophysiological processes associated with these adverse events.
Singh N, Singh R, Bowen RC, Abdel-Rahman MH, Singh AD. Uveal Melanoma in BAP1 Tumor Predisposition Syndrome: Estimation of Risk. Am J Ophthalmol 2021;224:172-177.Abstract
PURPOSE: To estimate point prevalence of uveal melanoma in the patients with germline BAP1 pathogenic variant. DESIGN: Cohort study with risk assessment using Bayesian analysis. METHODS: The point prevalence estimate was obtained by Bayes's rule of reverse conditional probabilities. The probability of uveal melanoma given that BAP1 mutation exists was derived from the prevalence of uveal melanoma, prevalence of germline BAP1 pathogenic variants, and the probability of germline BAP1 pathogenic variant given that uveal melanoma is present. Confidence intervals (CIs) for each variable were calculated as the mean of Bernoulli random variables and for the risk estimate, by the delta method. The age at diagnosis and the gender of the uveal melanoma patients with BAP1 germline pathogenic variants obtained from previous publications or from authors' unpublished cohort was compared with those in the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: The point prevalence of uveal melanoma in patients with the germline BAP1 pathogenic variants in the US population was estimated to be 2.8% (95% CI, 0.88%-4.81%). In the SEER database, the median age at diagnosis of uveal melanomas was 63 (range 3-99 years) with a male-to-female ratio of 1.01:1. In comparison, uveal melanoma cases with BAP1 germline pathogenic variants from the US population (n = 27) had a median age at diagnosis of 50.5 years (range 16-71). CONCLUSIONS: Quantification of the risk of developing uveal melanoma can enhance counseling regarding surveillance in patients with germline BAP1 pathogenic variant.
Sinha S, Singh RB, Dohlman TH, Taketani Y, Yin J, Dana R. Prevalence and Risk Factors Associated With Corneal Perforation in Chronic Ocular Graft-Versus-Host-Disease. Cornea 2021;40(7):877-882.Abstract
PURPOSE: To determine the prevalence and risk factors associated with corneal perforation in patients with chronic ocular graft-versus-host disease (oGVHD). METHODS: We reviewed the case records of 405 patients diagnosed with chronic oGVHD over 8 years at a single academic center and assessed the prevalence of corneal perforation in the cohort. We reviewed patient demographics, indication for and type of hematopoietic stem cell transplantation (HSCT), time elapsed between HSCT and perforation, and clinical characteristics including oGVHD severity scores, ocular comorbidities, and topical medications at the time of perforation. Data were analyzed to determine the characteristics of patients with corneal perforation and establish the risk factors. RESULTS: Of the 405 patients with chronic oGVHD, 15 (3.7%) developed a corneal perforation. The mean age of patients at the time of perforation was 64 ± 11 years and 10 (67%) were men. The median time to corneal perforation was 3.3 years post-HSCT. Although perforation occurred unilaterally in all cases, 44% had epithelial defects and 38% had stromal abnormalities in the contralateral eye. Of the patients with corneal perforation, 9 (60%) had a National Institute of Health oGVHD severity score of 2 and 6 (40%) had a score of 3. Patients with chronic oGVHD on antiglaucoma drops had a significantly higher risk of corneal perforation (P < 0.001). CONCLUSIONS: Corneal perforation is a rare but vision-threatening complication of chronic oGVHD. Our study emphasizes the need for frequent and long-term follow-up of patients with oGVHD regardless of the severity of disease. In particular, patients with chronic oGVHD on topical antiglaucoma medications should be monitored closely due to a higher risk for corneal perforation.
Sobel RK, Aakalu VK, Vagefi RM, Foster JA, Tao JP, Freitag SK, Wladis EJ, McCulley TJ, Yen MT. Orbital Radiation for Thyroid Eye Disease: A Report by the American Academy of Ophthalmology. Ophthalmology 2021;Abstract
PURPOSE: To review the current literature on the safety and efficacy of orbital radiation for the management of thyroid eye disease (TED). METHODS: A literature search was conducted last in February 2021 of the PubMed database to identify all articles published in the English language on original research that assessed the effect of orbital radiation on TED. The search identified 55 articles, and 18 met the inclusion criteria for this assessment. A panel methodologist then assigned a level of evidence rating for each study, and all of them were rated level III. RESULTS: Two large retrospective studies demonstrated the efficacy of radiation treatment, with or without corticosteroid use, in preventing or treating compressive optic neuropathy (CON). Three studies highlighted the role of orbital radiation therapy (RT) to facilitate the tapering of corticosteroids. Several other studies showed a possible role for RT to improve diplopia and soft tissue signs. CONCLUSIONS: Although no level I or level II evidence exists, the best available evidence suggests that orbital radiation, used with or without corticosteroids, is efficacious in preventing CON, improving motility restriction, and decreasing clinical activity in TED. Orbital radiation also may facilitate a corticosteroid taper. Together, these studies show that RT seems to modify the active phase of TED. Short-term risks of orbital radiation are minor, but long-term outcome data are lacking.
Sobrin L, Yu Y, Han S, Susarla G, Kempen JH, Hubbard RA, VanderBeek BL. Decreased risk of non-infectious anterior uveitis with statin therapy in a large healthcare claims database. Graefes Arch Clin Exp Ophthalmol 2021;259(9):2783-2793.Abstract
PURPOSE: The purpose of this study is to determine if statin therapy decreases the incidence of non-infectious uveitis (NIU) using a retrospective cohort study. METHODS: Patients enrolled in a national insurance plan who initiated statin (n = 711,734, statin cohort) or other lipid-lowering therapy (n = 148,044, non-statin cohort) were observed for NIU development. Incident NIU in the primary analysis was defined as a new diagnosis code for NIU followed by a second instance of a NIU code within 120 days. For the secondary outcome definition, a corticosteroid prescription or code for an ocular corticosteroid injection within 120 days of the NIU diagnosis code was used instead of the second NIU diagnosis code. Estimation of NIU incidence used multivariable Cox proportional hazards regression. The proportional hazards assumption was satisfied by creating two time periods of analysis, ≤ 150 and > 150 days. Subanalyses were performed by anatomic subtype. RESULTS: Overall, the primary outcome occurred 541 times over 690,465 person-years in the statin cohort and 103 times over 104,301 person-years in the non-statin cohort. No associations were seen in the ≤ 150-day analyses (p > 0.20 for all comparisons). However, after 150 days, the statin cohort was less likely to develop any uveitis [hazard ratio (HR) = 0.70, 95% confidence interval (CI): 0.51-0.97, P = 0.03] in the primary outcome analysis, but did not meet significance for the secondary outcome (HR = 0.85, 95% CI: 0.63-1.15, P = 0.30). Similarly, in the anatomic subtype analysis, after 150 days, the statin cohort was less likely to develop anterior uveitis (HR = 0.67, 95% CI: 0.47-0.97, P = 0.03) in the primary analysis, but the association did not reach significance for the secondary outcome (HR = 0.82, 95% CI: 0.56-1.20, P = 0.31). CONCLUSION: Our results suggest that statin therapy for > 150 days decreases the incidence of NIU.
Sobrin L, Yu Y, Li A, Kempen JH, Hubbard RA, VanderBeek BL. Angiotensin Converting Enzyme-Inhibitors and Incidence of Non-infectious Uveitis in a Large Healthcare Claims Database. Ophthalmic Epidemiol 2021;:1-6.Abstract
: To determine if angiotensin converting enzyme-inhibitors (ACE-I) alter the incidence of non-infectious uveitis (NIU). Patients in a large healthcare claims database who initiated ACE-I (n = 695,557) were compared to patients who initiated angiotensin receptor blockers (ARB, n = 354,295). A second comparison was also made between patients who initiated ACE-I (n = 505,958) and those who initiated beta-blockers (BB, n = 538,109). The primary outcome was incident NIU defined as a first diagnosis code for NIU followed by a second instance of a NIU code within 120 days. For the secondary outcome, a corticosteroid prescription or code for an ocular corticosteroid injection within 120 days of the NIU diagnosis code was used instead of the second NIU diagnosis code. Data were analyzed using Cox regression modeling with inverse probability of treatment weighting (IPTW). Sub-analyses were performed by anatomic subtype. When comparing ACE-I to ARB initiators, the hazard ratio (HR) for incident NIU was not significantly different for the primary outcome [HR = 0.95, 95% Confidence Interval (CI): 0.85-1.07, = .41] or secondary outcome [HR = 0.96, 95% CI: 0.86-1.07, = .44]. Similarly, in the ACE-I and BB initiators comparison, the HR for incident NIU was not significantly different comparing ACE-I and BB initiators for either outcome definition or any of the NIU anatomical subtypes. Our results suggest there is no evidence that ACE-I have a protective effect on NIU.
Sobrin L, Yu Y, Han S, Susarla G, Kempen JH, Hubbard RA, VanderBeek BL. Risk of Non-infectious Uveitis with Metformin Therapy in a Large Healthcare Claims Database. Ocul Immunol Inflamm 2021;:1-7.Abstract
PURPOSE: To determine if metformin is associated with noninfectious uveitis (NIU). METHODS: Patients in an insurance claims database who initiated metformin (n = 359,139) or other oral anti-diabetic medications (n = 162,847) were followed for NIU development. Both cohort and case-control analyses were performed to assess differing exposure lengths using Cox and conditional logistic regression, respectively. RESULTS: The hazard ratio (HR) for incident NIU was not significantly different between the metformin and non-metformin cohorts [HR = 1.19, 95% Confidence Interval (CI): 0.92-1.54, = .19]. The case control analysis similarly showed no association between any metformin use 2 years before the outcome date and NIU [odds ratio (OR) = 0.64, 95% CI: 0.39-1.04, = .07]. However, there was a protective 20 association between cumulative metformin duration [(445-729 days) adjusted OR (aOR) = 0.49, 95% CI: 0.27-0.90, = .02] and dosage (>390,000 mg aOR = 0.44, 95% CI: 0.25-0.78, = .001) compared with no metformin use. CONCLUSIONS: Our results suggest metformin use for longer durations may be protective of NIU onset.
Soeken TA, Ross AE, Kohane DS, Kuang L, Legault GL, Caldwell MC, Brundridge WL, Merkley MB, Ciolino JB, Townley RJ. Dexamethasone-Eluting Contact Lens for the Prevention of Postphotorefractive Keratectomy Scar in a New Zealand White Rabbit Model. Cornea 2021;40(9):1175-1180.Abstract
PURPOSE: To evaluate the safety and efficacy of an experimental dexamethasone-eluting contact lens (DCL) for the prevention of postphotorefractive keratectomy (PRK) corneal haze in a New Zealand White (NZW) rabbit model. METHODS: Both eyes of 29 NZW rabbits underwent PRK. The rabbits were randomized to one of the 5 study arms for 4 weeks: tarsorrhaphy only, tarsorrhaphy and bandage contact lens (BCL) replaced weekly, tarsorrhaphy and BCL for 1 week plus topical 0.1% dexamethasone ophthalmic solution (drops) for 4 weeks, tarsorrhaphy and BCL replaced weekly plus topical dexamethasone for 4 weeks, and tarsorrhaphy and DCL changed weekly for 4 weeks. Each week for 4 consecutive weeks postoperatively, the tarsorrhaphies were opened, the eyes underwent evaluation and imaging, and the tarsorrhaphies were replaced. Contact lenses were cultured on removal. Central corneal haze was assessed weekly with corneal densitometry. After 4 weeks, the animals were killed, and the eyes were enucleated for histopathologic analysis. RESULTS: The tarsorrhaphy only group displayed more haze with a greater change in optical densitometry from pre-op compared with the other treatment groups. There was no difference between the DCL group and the groups receiving a BCL and dexamethasone drops in densitometry or histopathology. No NZW rabbits developed clinical signs of infection, and cultures from DCLs and BCLs grew similar organisms. CONCLUSIONS: In the post-PRK rabbit model, DCLs worn weekly for 4 weeks were safe and as effective at preventing corneal haze as 0.1% dexamethasone drops applied 4 times a day for 4 weeks.
Soh Z, Yu M, Betzler BK, Majithia S, Thakur S, Tham YC, Wong TY, Aung T, Friedman DS, Cheng C-Y. The Global Extent of Undetected Glaucoma in Adults: A Systematic Review and Meta-analysis. Ophthalmology 2021;128(10):1393-1404.Abstract
TOPIC: Glaucoma is the leading cause of irreversible blindness, despite having good prognosis with early treatment. We evaluated the global extent of undetected glaucoma and the factors associated with it in this systematic review and meta-analysis. CLINICAL RELEVANCE: Undetected glaucoma increases the risk of vision impairment, which leads to detrimental effects on the quality-of-life and socioeconomic well-being of those affected. Detailed information on the extent and factors associated with undetected glaucoma aid in the development of public health interventions. METHODS: We conducted a systematic review and meta-analysis of population-based studies published between January 1, 1990, and June 1, 2020. Article search was conducted in online databases (PubMED, Web-of-Science), grey literatures (OpenGrey), and nongovernment organization reports. Our outcome measure was the proportion of glaucoma cases that were undetected previously. Manifest glaucoma included any form of glaucoma reported in the original studies and may include primary open-angle glaucoma (POAG), primary angle-closure-glaucoma, secondary glaucoma, or a combination thereof. Undetected glaucoma was defined as glaucoma cases that were undetected prior to diagnosis in the respective study. Random-effect meta-analysis was used to estimate the pooled proportion of undetected glaucoma. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Meta-analysis of Observational Studies in Epidemiology guidelines in our study. RESULTS: We identified 61 articles from 55 population-based studies (n = 189 359 participants; n = 6949 manifest glaucoma). Globally, more than half of all glaucoma cases were undetected previously on average in each geographical region. Africa (odds ratio [OR], 12.70; 95% confidence interval [CI], 4.91-32.86) and Asia (OR, 3.41; 95% CI, 1.63-7.16) showed higher odds of undetected glaucoma as compared with Europe. Countries with low Human Development Index (HDI; <0.55) showed a higher proportion of undetected manifest glaucoma as compared with countries of medium to very high HDI (≥0.55; all P < 0.001). In 2020, 43.78 million POAG cases were projected to be undetected, of which 76.7% were in Africa and Asia. DISCUSSION: Undetected glaucoma is highly prevalent across diverse communities worldwide and more common in Africa and Asia. Strategies to improve detection are needed to prevent excess visual disability and blindness resulting from glaucoma.
Sokol JT, Schechet SA, Komati R, Eliott D, Vavvas DG, Kaplan RI, Ittiara ST, Farooq AV, Sheth VS, MacCumber MW, Ke R, Gentile RC, Skondra D. Macular Hole Closure with Medical Treatment. Ophthalmol Retina 2021;5(7):711-713.

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