A Systematic Review of Clinical Trials in Uveitis: Lessons Learned.

PURPOSE: Clinical trials in uveitis have led to the expansion of therapeutic options for the management of non-infectious uveitis. The purpose of this systematic review is to investigate why some clinical trials have yielded successful results and regulatory approval of new therapies, and some have not. METHODS: A systematic literature search of the Pubmed/MEDLINE database and clinicaltrials.gov was performed from 2006 to 2021, according to the PRISMA guidelines. Phase III clinical trials of systemic and local therapies in adults with non-infectious intermediate, posterior, and panuveitis were included. RESULTS: A total of 79 clinical trials were collected from ClinicalTrials.gov and PubMed/MEDLINE database search. Based on the inclusion and exclusion criteria, 14 clinical trials were included. CONCLUSION: This review summarizes the study design, outcome measures, and results of recent phase III trials in non-infectious uveitis, in the interest of understanding limitations and rethinking new methods of defining endpoints in clinical trial design.

Computer Vision Syndrome in Undergraduate and Medical Students During the COVID-19 Pandemic.

Purpose: The purpose of this study was to evaluate Computer Vision Syndrome (CVS) in undergraduate and medical students since transitioning to online learning during the COVID-19 pandemic. Patients and Methods: This was a cross-sectional single center survey-based study using a validated CVS questionnaire (CVS-Q). The survey was distributed to 20,080 undergraduate students and 680 medical students at the University of Illinois at Chicago. The primary outcome measures were prevalence of CVS (based on CVS severity score of 6 or more), frequency of CVS and intensity of CVS symptoms. Results: The survey was completed by 2300 undergraduate students (11.4% response rate) and 154 medical students (22.6% response rate). The prevalence of CVS was 77.1% in undergraduate students and 69.1% in medical students. CVS-Q severity scores were highest for headaches and eye dryness, with over half of students reporting worsening of symptoms since March 2020. Increased time spent on online learning (undergraduate: P <0.001, medical: P = 0.018), blue light glasses usage (undergraduate: P <0.001, medical: P = 0.0015), and increased number of device usage were associated with higher CVS severity scores (undergraduate: P <0.001, medical: P = 0.0032). Conclusion: CVS among undergraduate and medical students has increased since the start of the COVID-19 pandemic. More focus should be placed on the management of CVS for students in higher education. Physicians should be cognizant of the consequences of online learning and be proactive about providing advice regarding preventative measures.

An ophthalmology professionalism survey tool: outcomes from a multi-center study in Central India.

Purpose: To describe a professionalism survey tool and its use to assess knowledge of medical professionalism in ophthalmology training programs in Central India. Settings and Design: Multi-center survey study. Methods: A validated 33-question, scenario-based survey addressing professionalism attributes was administered at five centers in central India. The attributes tested included "personal characteristics," "physician-patient relationships," "workplace practice and relationships," and "socially responsible behaviors." A mean attribute score (%) was calculated and compared to "gold standard" responses by a group of expert senior ophthalmologists (100% agreement for responses). Results: A total of 225 participants completed the survey; 124 residents, 47 fellows, and 54 consultants (98.4% response rate). The total mean attribute score was 80.7 ± 9.1 (min 16.67, max 100). There was variation in the mean attribute score by professionalism attribute (P < 0.001), and a trend toward higher mean attribute scores for consultants compared to trainees across all attribute groups. The scores for "personal characteristics" (93 ± 9.7) and "physician-patient relationship" (82 ± 15.8) were the highest, whereas scores for "socially responsible behaviors" (73.9 ± 18.6) and "workplace practices" were low (72 ± 13). Conclusions: There is a generally high level of professionalism knowledge among ophthalmologists in central India. The results suggest that experience does impact knowledge of professionalism. Potential for improvement in professionalism exists in around "workplace practices", and around "socially responsible behaviors". These findings may serve as a valuable discussion starter and teaching tool to enhance professionalism in ophthalmology training programs.

Quantitative contrast sensitivity test to assess visual function in central serous chorioretinopathy.

BACKGROUND: To characterise the contrast sensitivity function (CSF) in central serous chorioretinopathy (CSCR) compared with healthy controls using novel computerised contrast sensitivity (CS) testing with active learning algorithms. METHODS: Prospective observational study measuring CSF in CSCR eyes and controls using the Manifold Platform (Adaptive Sensory Technology, San Diego, California). Mixed effects multivariate regression models were used. Outcomes included area under the log CSF (AULCSF), CS thresholds at 1, 1.5, 3, 12 and 18 cycles per degree (cpd) and best-corrected visual acuity (BCVA). Associations of contrast outcomes with structural findings on optical coherence tomography (OCT) and subjective symptomatology were investigated. RESULTS: Forty CSCR eyes and 89 controls were included with median BCVA logarithm of median angle of resolution 0.10 (20/25) versus 0.00 (20/20), respectively (p=0.01). When accounting for age, CSCR was associated with significantly reduced median AULCSF (p=0.02, ß=-0.14) and reduced CS thresholds at 6 cpd (p=0.009, ß=-0.18), 12 cpd (p<0.001, ß=-0.23) and 18 cpd (p=0.04, ß=-0.09), versus controls. Within the CSCR group, subjectively perceived visual impairment (N=22) was associated with significantly decreased CS thresholds at all spatial frequencies and in AULCSF compared with asymptomatic CSCR eyes (N=18). Ellipsoid zone attenuation and subfoveal fluid on OCT were associated with decreased AULCSF and CS thresholds specifically at 3, 6 and 12 cpd, whereas presence of extrafoveal fluid at 1.5 and 3 cpd. CONCLUSION: Contrast sensitivity is significantly reduced in CSCR, and strongly correlates with subjective visual impairment. Different structural biomarkers correlate with contrast thresholds reductions at different spatial frequencies.

Epidemiology and Risk Factors in Non-infectious Uveitis: A Systematic Review.

Purpose: Non-infectious uveitis is a leading cause of vision loss in the developed world. The purpose of this systematic review is to investigate the epidemiology and risk factors of non-infectious uveitis over the last 50 years. Methods: A systematic literature search of Pubmed/MEDLINE database was performed in the 50-year period from January 1971 to January 2021, according to the PRISMA guidelines. Studies that assessed the epidemiology and risk factors for non-infectious uveitis were included. Results: Few epidemiologic studies focus specifically on non-infectious uveitis. In the Unites States, the estimated prevalence of non-infectious uveitis is 121/100,000. The incidence and prevalence varies considerably worldwide. Females and the working age group (20-50 years) appear to be the most affected. Smoking and vitamin D deficiency are the biggest risk factors for non-infectious uveitis, while pregnancy appears to be protective. Additional risk factors include presence of other autoimmune diseases (thyroid disease, diabetes, celiac), pre-eclampsia/eclampsia, psychological stress, and certain medications (bisphosphonates, immune checkpoint inhibitors, female hormone therapy, and etanercept). Discussion: Our systematic review summarizes the incidence and prevalence of non-infectious uveitis and associated modifiable and non-modifiable risk factors.

Active Learning of Contrast Sensitivity to Assess Visual Function in Macula-off Retinal Detachment.

PURPOSE: To characterize the contrast sensitivity function (CSF) in patients with successful repair of macula-off rhegmatogenous retinal detachment (RD) using an adaptive computerized contrast testing device. METHODS: CSF was prospectively measured in macula-off RD patients following successful repair and age-matched controls at W. K. Kellogg Eye Center and Massachusetts Eye and Ear, employing the active learning device Manifold Contrast Vision Meter (Adaptive Sensory Technology, San Diego, CA). Outcome measures included average area under the CSF curve (AULCSF), CS thresholds at 1-18 cycles per degree (cpd) and best correctd visual acuity (BCVA) in RD eyes fellow eyes and controls. A sub-analysis was performed in eyes with BCVA of 20/30 or better. RESULTS: Twenty-three macula-off RD eyes status post repair, fellow healthy eyes and 45 age-matched control eyes underwent CSF testing. The mean BCVA of the 23 RD eyes was 0.250 logMAR, significantly reduced compared to fellow eyes 0.032 (p<0.001) and controls 0.026 (p< 0.00001). There was a statistically significant reduction in AULCSF in RD eyes compared to the fellow eyes (p<0.0001) and to age-matched controls (Z-score -0.90, p<0.0001) and CSF reduction across all spatial frequencies. In the 15 RD eyes with BCVA of 20/30 or better, the mean CSF was significantly reduced compared to fellow eyes (p=0.0158) and controls (p=0.0453). CONCLUSIONS: CSF in macula-off RD eyes following repair was significantly reduced compared to fellow eyes and age-matched controls. CSF seems to be a promising visual function endpoint with potential applications in the clinical practice and future clinical trials.

Disorganization of Retinal Inner Layers (DRIL) and Neuroretinal Dysfunction in Early Diabetic Retinopathy.

Purpose: To elucidate the relationship between disorganization of retinal inner layers (DRILs) and retinal function in diabetic patients without diabetic retinopathy (DR) and with nonproliferative DR, but without diabetic macular edema (DME). Methods: Fifty-seven participants with diabetes mellitus (DM) and 18 healthy controls underwent comprehensive ophthalmic examination, fundus photography, and spectral-domain optical coherence tomography. Scans of the fovea were evaluated for the presence of DRIL. Retinal function was evaluated using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity, the quick contrast sensitivity function (qCSF) on the AST Sentio Platform, short-wavelength automated perimetry (SWAP), standard automated perimetry (SAP), and frequency doubling perimetry (FDP). ANOVA and Kruskal-Wallis were used to compare retinal function in subjects with and without DRIL. Tukey-Kramer test and Wilcoxon were used for post hoc analysis. Results: DRIL was identified in 9 of 57 diabetic subjects. DRIL subjects had higher body mass index and longer diabetes duration compared to diabetic subjects without DRIL (P = 0.03 and P = 0.009, respectively). Subjects with DRIL had reduced ETDRS visual acuity (P = 0.003), contrast sensitivity function (P = 0.0003), and SAP performance (PSD, P < 0.0001) compared to controls and diabetic subjects without DRIL. Structural analysis revealed inner retinal thinning, and some outer retinal thinning, associated with DRIL. Conclusions: Diabetic subjects with DRIL have reduced retinal function compared to those without DRIL, and defective retinal lamination may be an early cellular consequence of diabetes responsible for this in some patients. Following further longitudinal studies, DRIL may be a readily available and reliable structural biomarker for reduced retinal function in early diabetic neuroretinal disease.

Multidimensional Functional and Structural Evaluation Reveals Neuroretinal Impairment in Early Diabetic Retinopathy.

Purpose: To test whether quantitative functional tests and optical coherence tomography (OCT)-defined structure can serve as effective tools to diagnose and monitor early diabetic neuroretinal disease. Methods: Fifty-seven subjects with diabetes (23 without diabetic retinopathy [no DR], 19 with mild nonproliferative diabetic retinopathy [mild NPDR], 15 with moderate to severe [moderate NPDR]), and 18 controls underwent full ophthalmic examination, fundus photography, spectral-domain optical coherence tomography (SD-OCT), e-ETDRS (Early Treatment Diabetic Retinopathy Study) acuity, and the quick contrast sensitivity function (qCSF) method. Perimetry testing included short-wavelength automated perimetry (SWAP), standard automated perimetry (SAP), frequency doubling perimetry (FDP), and rarebit perimetry (RBP). Results: ETDRS acuity and RBP were not sensitive for functional differences among subjects with diabetes. AULCSF, a metric of qCSF, was reduced in diabetics with moderate compared to mild NPDR (P = 0.03), and in subjects with no DR compared to controls (P = 0.04). SWAP and SAP mean deviation (MD) and foveal threshold (FT) were reduced in moderate compared to mild NPDR (SWAP, MD P = 0.002, FT P = 0.0006; SAP, MD P = 0.02, FT P = 0.007). FDP 10-2 showed reduced MD in moderate compared to mild NPDR (P = 0.02), and FDP 24-2 revealed reduced pattern standard deviation (PSD) in mild NPDR compared to no DR (P = 0.02). Structural analysis revealed thinning of the ganglion cell layer and inner plexiform layer (GCL+IPL) of moderate NPDR subjects compared to controls. The thinner GCL+IPL correlated with impaired retinal function. Conclusions: This multimodal testing analysis reveals insights into disruption of the neuroretina in diabetes and may accelerate the testing of novel therapies.

Peripheral Visual Fields in ABCA4 Stargardt Disease and Correlation With Disease Extent on Ultra-widefield Fundus Autofluorescence.

PURPOSE: To evaluate the disease extent on ultra-widefield fundus autofluorescence (UWF-FAF) in patients with ABCA4 Stargardt disease (STGD) and correlate these data with functional outcome measures. DESIGN: Retrospective cross-sectional study. METHODS: Setting: Kellogg Eye Center, University of Michigan. STUDY POPULATION: Sixty-five patients with clinical diagnosis and proven pathogenic variants in the ABCA4 gene. Observational Procedures: The UWF-FAF images were obtained using Optos (200 degrees) and classified into 3 types. Functional testing included kinetic widefield perimetry, full-field electroretinogram (ffERG), and visual acuity (VA). All results were evaluated with respect to UWF-FAF classification. MAIN OUTCOME MEASURES: Classification of UWF-FAF; area comprising the I4e, III4e, and IV4e isopters; ffERG patterns; and VA. RESULTS: For UWF-FAF, 27 subjects (41.5%) were classified as type I, 17 (26.2%) as type II, and 21 (32.4%) as type III. The area of each isopter correlated inversely with the extent of the disease and all isopters were able to detect differences among UWF-FAF types (IV4e, P = .0013; III4e, P = .0003; I4e, P < .0001 = 3.93e-8). ffERG patterns and VA were also different among the 3 UWF-FAF types (P < .001 = 6.61e-6 and P < .001 = 7.3e-5, respectively). CONCLUSION: Patients with widespread disease presented with more constriction of peripheral visual fields and had more dysfunction on ffERG and worse VA compared to patients with disease confined to the macula. UWF-FAF images may provide information for estimating peripheral and central visual function in STGD.