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Fan N-W, Li J, Mittal SK, Foulsham W, Elbasiony E, Huckfeldt RM, Chauhan SK, Chen Y. Characterization of Clinical and Immune Responses in an Experimental Chronic Autoimmune Uveitis Model. Am J Pathol 2021;191(3):425-437.Abstract
Autoimmune uveitis is a sight-threatening intraocular inflammatory disease. For >30 years, the mouse model of experimental autoimmune uveitis has been employed to investigate disease mechanisms and test immunotherapeutic approaches. However, inflammation in this model is self-limited, and does not replicate the chronic, insidious nature prevalent in the human disease. Herein, a robust and reliable model of chronic autoimmune uveitis was developed and characterized in two strains of wild-type mice by modifying interphotoreceptor retinoid-binding protein dose and peptide fragments from conventional experimental autoimmune uveitis models. In both of these murine strains, immunization with our modified protocols resulted in a slowly progressive uveitis, with retinal scars and atrophy observed in the chronic stage by fundoscopy. Optical coherence tomography demonstrated decreased retinal thickness in chronic autoimmune uveitis mice, and electroretinography showed significantly reduced amplitudes of dark-adapted a- and b-waves and light-adapted b-waves. Histologic examination revealed prominent choroiditis with extensive retinal damage. Flow cytometry analysis showed substantially increased numbers of CD44IL-17IFN-γ memory T-helper 17 (Th17) cells in the retina, cervical lymph nodes, inguinal lymph nodes, and spleen. These data establish new modified protocols for inducing chronic uveitis in wild-type mice, and demonstrate a predominant memory Th17 cell response, suggesting an important role for memory Th17 cells in driving chronic inflammation in autoimmune uveitis.
Lu Y, Wang JC, Cui Y, Zhu Y, Zeng R, Lu ES, Katz R, Husain D, Vavvas DG, Kim LA, Miller JW, Miller JB. A quantitative comparison of four optical coherence tomography angiography devices in healthy eyes. Graefes Arch Clin Exp Ophthalmol 2021;259(6):1493-1501.Abstract
PURPOSE: Optical coherence tomography angiography (OCT-A) is a novel imaging modality for the diagnosis of chorioretinal diseases. A number of FDA-approved OCT-A devices are currently commercially available, each with unique algorithms and scanning protocols. Although several published studies have compared different combinations of OCT-A machines, there is a lack of agreement on the consistency of measurements across OCT-A devices. Therefore, we conducted a prospective quantitative comparison of four available OCT-A platforms. METHODS: Subjects were scanned on four devices: Optovue RTVue-XR, Heidelberg Spectralis OCT2 module, Zeiss Plex Elite 9000 Swept-Source OCT, and Topcon DRI-OCT Triton Swept-Source OCT. 3 mm × 3 mm images were utilized for analysis. Foveal avascular zone (FAZ) area was separately and independently measured by two investigators. Fractal dimension (FD), superficial capillary plexus (SCP), and deep capillary plexus (DCP) vessel densities (VD) were calculated from binarized images using the Fiji image processing software. SCP and DCP VD were further calculated after images were skeletonized. Repeated measures ANOVA, post hoc tests, and interclass correlation coefficient (ICC) were performed for statistical analysis. RESULTS: Sixteen healthy eyes from sixteen patients were scanned on the four devices. Images of five eyes from the Triton device were excluded due to poor image quality; thus, the authors performed two sets comparisons, one with and one without the Triton machine. FAZ area showed no significant difference across devices with an ICC of > 95%. However, there were statistically significant differences for SCP and DCP VD both before and after skeletonization (p < 0.05). Fractal analysis revealed no significant difference of FD at the SCP; however, a statistically significant difference was found for FD at the DCP layer (p < 0.05). CONCLUSIONS: The results showed that FAZ measurements were consistent across all four devices, while significant differences in VD and FD measurements existed. Therefore, we suggest that for both clinical follow-up and research studies, FAZ area is a useful parameter for OCT-A image analysis when measurements are made on different machines, while VD and FD show significant variability when measured across devices.
Franco J, Lee NG. Granulomatosis with polyangiitis presenting as recurrent, multifocal orbital myositis. Orbit 2021;40(6):529-531.Abstract
A 43-year-old woman was referred with a 10 month history of persistent pain in the left orbit. Two years prior, she experienced similar pain in the right orbit. Magnetic resonance imaging (MRI) at the time revealed an enlarged right medial rectus muscle. She was diagnosed with idiopathic orbital myositis and was successfully treated with oral corticosteroids. A year later, she developed symptoms in the left orbit with similar imaging findings. For ten months, she remained on high dose corticosteroids for presumed left medial rectus myositis before presenting to our service. Computed tomography (CT) imaging after corticosteroid taper revealed enlarged left medial rectus and left lateral rectus muscles. Orbital biopsy established a diagnosis of granulomatosis with polyangiitis (GPA), for which she was successfully treated with rituximab. This case underscores the importance of not only proceeding with biopsy in atypical cases of orbital myositis but to also taper steroids prior to biopsy.
Chen CL, McLeod SD, Lietman TM, Shen H, Boscardin JW, Peggy Chang H-Y, Whooley MA, Gelb AW, Lee SJ, Dudley AR. Preoperative Medical Testing and Falls in Medicare Beneficiaries Awaiting Cataract Surgery. Ophthalmology 2021;128(2):208-215.Abstract
PURPOSE: Delaying cataract surgery is associated with an increased risk of falls, but whether routine preoperative testing delays cataract surgery long enough to cause clinical harm is unknown. We sought to determine whether the use of routine preoperative testing leads to harm in the form of delayed surgery and falls in Medicare beneficiaries awaiting cataract surgery. DESIGN: Retrospective, observational cohort study using 2006-2014 Medicare claims. PARTICIPANTS: Medicare beneficiaries 66+ years of age with a Current Procedural Terminology claim for ocular biometry. METHODS: We measured the mean and median number of days between biometry and cataract surgery, calculated the proportion of patients waiting ≥ 30 days or ≥ 90 days for surgery, and determined the odds of sustaining a fall within 90 days of biometry among patients of high-testing physicians (testing performed in ≥ 75% of their patients) compared with patients of low-testing physicians. We also estimated the number of days of delay attributable to high-testing physicians. MAIN OUTCOME MEASURES: Incidence of falls occurring between biometry and surgery, odds of falling within 90 days of biometry, and estimated delay associated with physician testing behavior. RESULTS: Of 248 345 beneficiaries, 16.4% were patients of high-testing physicians. More patients of high-testing physicians waited ≥ 30 days and ≥ 90 days to undergo surgery (31.4% and 8.2% vs. 25.0% and 5.5%, respectively; P < 0.0001 for both). Falls before surgery in patients of high-testing physicians increased by 43% within the 90 days after ocular biometry (1.0% vs. 0.7%; P < 0.0001). The adjusted odds ratio of falling within 90 days of biometry in patients of high-testing physicians versus low-testing physicians was 1.10 (95% confidence interval [CI], 1.03-1.19; P = 0.008). After adjusting for surgical wait time, the odds ratio decreased to 1.07 (95% CI, 1.00-1.15; P = 0.06). The delay associated with having a high-testing physician was approximately 8 days (estimate, 7.97 days; 95% CI, 6.40-9.55 days; P < 0.0001). Other factors associated with delayed surgery included patient race (non-White), Northeast region, ophthalmologist ≤ 40 years of age, and low surgical volume. CONCLUSIONS: Overuse of routine preoperative medical testing by high-testing physicians is associated with delayed surgery and increased falls in cataract patients awaiting surgery.
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.
Ashraf M, Shokrollahi S, Pisig AU, Sampani K, AbdelAl O, Cavallerano JD, Robertson G, Fleming A, van Hemert J, Pitoc CM, Sun JK, Aiello LP, Silva PS. Retinal Vascular Caliber Association with Nonperfusion and Diabetic Retinopathy Severity Depends on Vascular Caliber Measurement Location. Ophthalmol Retina 2021;5(6):571-579.Abstract
PURPOSE: To evaluate the association of retinal nonperfusion and diabetic retinopathy (DR) severity with location of vascular caliber measurement using ultrawide field (UWF) imaging. DESIGN: Retrospective image review. PARTICIPANTS: Adults with diabetes mellitus. METHODS: All images from subjects with same-day UWF fluorescein angiography (FA) and color imaging were evaluated. Predominantly peripheral lesions (PPL) and DR severity were graded from UWF color images. Nonperfusion was quantified using UWF-FA in defined retinal regions [posterior pole (PP), mid-periphery (MP), far-periphery (FP)]. Retinal vessel calibers were measured at an optic disc centered inner and outer zone. MAIN OUTCOME MEASURES: Nonperfusion index (NPI) in the PP, MP and FP. Mean arteriole and venule diameter in the inner and outer zones. RESULTS: Two hundred eighty-five eyes of 193 patients (24.9% mild nonproliferative DR [NPDR], 22.8% moderate NPDR, 37.5% severe NPDR and 14.7% proliferative DR [PDR]) were reviewed. No significant associations between inner zone arteriolar diameter and retinal NPI overall or in any retinal region. In the outer zone, eyes with thinnest arteriolar calibers (quartile 1) were associated with a 1.7- to 2.4-fold nonperfusion increase across all retinal regions compared to the remaining eyes (P = 0.002 [PP] to 0.048 [FP]). In the outer zone, the percentage of eyes in the thinnest quartile of retinal arteriolar diameter increased with worsening DR severity (mild NPDR: 10% vs PDR: 31%, P = 0.007). This association was not observed when measured within the inner zone (P = 0.129). All venular caliber associations were not statistically significant when corrected for potentially confounding factors. Thinner outer zone retinal arteriolar caliber (quartile 1) was more common in eyes with PPL compared to eyes without PPL (34.1% vs 20.8%, P = 0.017) as were thicker outer venular calibers (quartile 4) (33% vs 21.3%, P = 0.036). Presence of PPL was associated with thinner outer zone arteriolar caliber (109.7 ± 26.5μm vs 123.0 ± 29.5μm, P = 0.001). CONCLUSIONS: The association of vascular caliber with nonperfusion and DR severity differs based upon the retinal location at which vascular caliber is measured. Peripheral arterial narrowing is associated with increasing nonperfusion, worsening DR severity and presence of PPL. In contrast, inner zone retinal arteriolar caliber is not associated with these findings.
Bakshi SK, Lin SR, Ting DSW, Chiang MF, Chodosh J. The era of artificial intelligence and virtual reality: transforming surgical education in ophthalmology. Br J Ophthalmol 2021;105(10):1325-1328.Abstract
Training the modern ophthalmic surgeon is a challenging process. Microsurgical education can benefit from innovative methods to practice surgery in low-risk simulations, assess and refine skills in the operating room through video content analytics, and learn at a distance from experienced surgeons. Developments in emerging technologies may allow us to pursue novel forms of instruction and build on current educational models. Artificial intelligence, which has already seen numerous applications in ophthalmology, may be used to facilitate surgical tracking and evaluation. Within immersive technology, growth in the space of virtual reality head-mounted displays has created intriguing possibilities for operating room simulation and observation. Here, we explore the applications of these technologies and comment on their future in ophthalmic surgical education.
Ma KK, Kinde B, Doan T, Jacobs DS, Ong Tone S. Dual Molecular Diagnosis of Microsporidia (Encephalitozoon hellem) Keratoconjunctivitis in an Immunocompetent Adult. Cornea 2021;40(2):242-244.Abstract
PURPOSE: To report a case of microsporidia (Encephalitozoon hellem) keratoconjunctivitis acquired through avian transmission in an immunocompetent adult, diagnosed by metagenomic deep sequencing (MDS), and confirmed by polymerase chain reaction. METHODS: A case report. RESULTS: An 18-year-old woman was referred with unilateral keratoconjunctivitis unresponsive to topical and systemic therapy after exposure to birdcage debris. Slit-lamp examination of the left eye revealed a follicular papillary reaction of the palpebral conjunctiva and multiple corneal punctate epithelial opacities that stained minimally with fluorescein. In vivo confocal microscopy revealed bright double-walled structures and smaller bright round structures in the superficial epithelial debris and epithelium. Molecular diagnosis with MDS of E. hellem was confirmed by polymerase chain reaction. Clinical resolution and normalization of in vivo confocal microscopy was observed after a 6-week course of topical azithromycin. The patient elected a 3-week course of topical voriconazole 1% for definitive antimicrosporidial treatment, with no evidence of persistent infection 1 month later. CONCLUSIONS: Microsporidial (E. hellem) keratoconjunctivitis can occur through avian transmission in immunocompetent hosts. Topical azithromycin may be effective against this pathogen. MDS has utility in the diagnosis of atypical keratoconjunctivitis.
Swan G, Goldstein RB, Savage SW, Zhang L, Ahmadi A, Bowers AR. Automatic processing of gaze movements to quantify gaze scanning behaviors in a driving simulator. Behav Res Methods 2021;53(2):487-506.Abstract
Eye and head movements are used to scan the environment when driving. In particular, when approaching an intersection, large gaze scans to the left and right, comprising head and multiple eye movements, are made. We detail an algorithm called the gaze scan algorithm that automatically quantifies the magnitude, duration, and composition of such large lateral gaze scans. The algorithm works by first detecting lateral saccades, then merging these lateral saccades into gaze scans, with the start and end points of each gaze scan marked in time and eccentricity. We evaluated the algorithm by comparing gaze scans generated by the algorithm to manually marked "consensus ground truth" gaze scans taken from gaze data collected in a high-fidelity driving simulator. We found that the gaze scan algorithm successfully marked 96% of gaze scans and produced magnitudes and durations close to ground truth. Furthermore, the differences between the algorithm and ground truth were similar to the differences found between expert coders. Therefore, the algorithm may be used in lieu of manual marking of gaze data, significantly accelerating the time-consuming marking of gaze movement data in driving simulator studies. The algorithm also complements existing eye tracking and mobility research by quantifying the number, direction, magnitude, and timing of gaze scans and can be used to better understand how individuals scan their environment.
Hu A, Gu SZ, Friedman DS, Cao K, Wang N. Six-Year Incidence and Causes of Low Vision and Blindness in a Rural Chinese Adult Population: The Handan Eye Study. Ophthalmic Epidemiol 2021;28(2):160-168.Abstract
PURPOSE: To determine the six-year incidence, risk factors, and causes of visual impairment in a Chinese population. METHODS: This was a population-based study of eye disease in Chinese adults in a rural district of Handan in China. 6,830 individuals were invited to participate in 2006 and 5,394 returned for follow-up in 2012. All participants underwent standardized eye examinations. Visual impairment was defined according to WHO criteria. The incidence of visual impairment was age- and gender-standardized to the 2010 China Census. Multivariable logistic regression analysis was used to determine risk factors for visual impairment. RESULTS: The leading causes of visual impairment were cataract and refractive error. Based on (PVA), the six-year incidence rates of low vision and blindness were 5.2% and 0.5%, respectively. Incidence of low vision was associated with older age ( < .001), less education ( < .001), diabetes ( < .05), and lower BMI ( < .001). The incidence of blindness was associated with diabetes ( < .05). Based on (BCVA), the six-year incidence rates of low vision and blindness were 0.8% and 0.1%, respectively. Incidence of low vision was associated with older age ( < .001) and lower BMI ( < .05). None of these factors were associated with the incidence of blindness. CONCLUSION: In Handan, the incidence of visual impairment was high and associated with older age, less education, diabetes, and lower BMI. The majority of cases were due to unoperated cataract and uncorrected refractive error, reflecting the need for improved eye care in this region.
Marmamula S, Barrenakala NR, Challa R, Kumbham TR, Modepalli SB, Yellapragada R, Bhakki M, Reddy JC, Friedman DS, Khanna RC. Visual outcomes after cataract surgery among the elderly residents in the 'homes for the aged' in South India: the Hyderabad Ocular Morbidity in Elderly Study. Br J Ophthalmol 2021;105(8):1087-1093.Abstract
BACKGROUND/AIM: To report visual outcomes and factors associated with good visual outcomes after cataract surgery among the elderly residents in 'homes for the aged' in Hyderabad, India. METHODS: Individuals aged ≥60 years were recruited from 41 'homes for the aged'. All participants had a detailed eye examinations including visual acuity (VA) assessment , refraction, slit-lamp examination and fundus imaging by trained professionals. A detailed history of cataract surgery was recorded. Multivariate logistic regression was used to determine the factors associated with good visual outcomes after cataract surgery which was defined as presenting VA of 6/18 or better in the operated eye. Visual impairment (VI) is defined as presenting VA worse than 6/18 in the operated eye. RESULTS: 1215 eyes of 703 individuals had cataract surgery. The mean age of these participants was 77.5 years (SD: 8.2 years; range: 60-108 years), 66.8% were women, 29.9% reported diabetes and 61% reported hypertension. 406/1215 (33.4%; 95% CI 30.8 to 36.1) eyes had VI after cataract surgery. Posterior capsular opacification (31.8%; n=129) was the leading cause of VI followed by uncorrected refractive error (24.1%; n=98). The prevalence of good outcomes was 66.6% (95% CI 63.8 to 69.2). On applying multivariable analysis, younger age, self-reported hypertension, independent mobility, surgery in a non-government (as opposed to private) hospital and undergoing paid surgery were associated with good outcomes. CONCLUSIONS: One-third of the eyes of elderly individuals living in homes for the aged that had previously undergone cataract surgery had VI. Regular eye examinations with the provision of laser capsulotomy and appropriate refractive correction can substantially improve their vision.
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.
Franco JJ, Reyes Luis JL, Rahim S, Greenstein S, Pineda R. Survival of the fittest: phacoemulsification outcomes in four corneal transplants by Dr Ramon Castroviejo. Br J Ophthalmol 2021;105(8):1076-1081.Abstract
AIM: To evaluate and report the outcomes following phacoemulsification on four eyes, 45 years or more after corneal transplantation. METHODS: A retrospective case series of four eyes in three patients (P1, P2, P3), undergoing phacoemulsification at least 45 years after corneal transplantation by Dr Ramon Castroviejo. Corneal graft survival outcome measures included central corneal thickness (CCT), best-corrected visual acuity (BCVA), corneal clarity and endothelial cell count (ECC). RESULTS: Phacoemulsification was successfully completed in all four cases with no instances of graft failure during the postoperative follow-up period, which ranged from 17 months to 76 months. At the conclusion of the follow-up period, all four grafts remained clear, and BCVA remained better than or similar to preoperative values. Long-term follow-up revealed no meaningful changes in CCT after phacoemulsification. All but one case experienced a decrease in ECC, with ECC values in the four cases ranging from 538 cells/mm2 to 1436 cells/mm2 at the conclusion of postoperative follow-up. CONCLUSION: Limited data have been published on the long-term survival of corneal grafts after intraocular surgery, especially for extremely 'mature' corneal transplants. This case series demonstrates that with appropriate preoperative, intraoperative and postoperative measures, successful phacoemulsification can be performed in these cases with excellent long-term results.

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