Andrew Berneshawi

All Publications

• Glaucoma Home Self-Testing Using VR Visual Fields and Rebound Tonometry Versus In-Clinic Perimetry and Goldmann Applanation Tonometry: A Pilot Study. Translational vision science & technology Berneshawi, A. R., Shue, A., Chang, R. T. 2024; 13 (8): 7

  Abstract

  This pilot study aimed to assess the feasibility, accuracy, and repeatability of unsupervised, at-home, multi-day glaucoma testing using the Olleyes VisuALL Virtual Reality Platform (VRP) and the iCare HOME handheld self-tonometer.Participants were trained to use two U.S. Food and Drug Administration-registered or approved devices before conducting self-tests at home over 3 consecutive days. The iCare HOME intraocular pressure (IOP) measurements were collected four times daily per eye, and VRP visual field tests were performed once daily. The results were compared with one in-clinic Humphrey Field Analyzer (HFA) visual field test performed on the day of device training, iCare HOME measurements by the trainer, and the last five Goldmann applanation tonometer (GAT) results.Of 15 enrolled participants, nine of them (60%) completed the study. The six excluded participants could not self-measure using iCare HOME. There was significant correlation between the average mean deviation (MD) values of the at-home VRP tests and in-clinic HFA test (r2 = 0.8793, P < 0.001). Additionally, the average of the sensitivities in five of six Garway-Heath sectors were significantly correlated. VRP test duration was also shorter than in-clinic HFA testing (P < 0.001). Finally, at-home tonometry yielded statistically similar values compared to trainer-obtained iCare HOME values. The mean and range of at-home tonometry were also statistically similar to those for in-clinic GAT, but at-home tonometry demonstrated higher maximum IOP values (P = 0.0429).Unsupervised, at-home, multi-day glaucoma testing using two devices resulted in the capture of higher maximum IOPs than in the clinic and good MD correlation of VRP with HFA. However, 40% of participants could not self-measure IOP using iCare HOME.The study findings suggest that at-home remote glaucoma monitoring correlates with in-office testing and could provide additional information for glaucoma management, although patients had more difficulty with the iCare HOME than the VRP.

  View details for DOI 10.1167/tvst.13.8.7

  View details for PubMedID 39102241

• Primary cilia formation requires the Leigh syndrome-associated mitochondrial protein NDUFAF2. The Journal of clinical investigation Lo, C. H., Liu, Z., Chen, S., Lin, F., Berneshawi, A. R., Yu, C. Q., Koo, E. B., Kowal, T. J., Ning, K., Hu, Y., Wang, W. J., Liao, Y. J., Sun, Y. 2024; 134 (13)

  Abstract

  Mitochondria-related neurodegenerative diseases have been implicated in the disruption of primary cilia function. Mutation in an intrinsic mitochondrial complex I component NDUFAF2 has been identified in Leigh syndrome, a severe inherited mitochondriopathy. Mutations in ARMC9, which encodes a basal body protein, cause Joubert syndrome, a ciliopathy with defects in the brain, kidney, and eye. Here, we report a mechanistic link between mitochondria metabolism and primary cilia signaling. We discovered that loss of NDUFAF2 caused both mitochondrial and ciliary defects in vitro and in vivo and identified NDUFAF2 as a binding partner for ARMC9. We also found that NDUFAF2 was both necessary and sufficient for cilia formation and that exogenous expression of NDUFAF2 rescued the ciliary and mitochondrial defects observed in cells from patients with known ARMC9 deficiency. NAD+ supplementation restored mitochondrial and ciliary dysfunction in ARMC9-deficient cells and zebrafish and ameliorated the ocular motility and motor deficits of a patient with ARMC9 deficiency. The present results provide a compelling mechanistic link, supported by evidence from human studies, between primary cilia and mitochondrial signaling. Importantly, our findings have significant implications for the development of therapeutic approaches targeting ciliopathies.

  View details for DOI 10.1172/JCI175560

  View details for PubMedID 38949024

• Repeatability of a Virtual Reality Headset Perimeter in Glaucoma and Ocular Hypertensive Patients. Translational vision science & technology Nascimento E Silva, R., Kim, J. A., Li, Y., Chen, C., Chaudhry, A. F., Berneshawi, A. R., Zhang, M., Villarreal, A., Liu, J., Shue, A., Chang, D. S., Chang, R. T. 2024; 13 (6): 14

  Abstract

  The VisuALL S is an automated, static threshold, virtual reality-based perimeter for mobile evaluation of the visual field. We examined same-day and 3-month repeatability.Adult participants with a diagnosis of glaucoma or ocular hypertension underwent two VisuALL 24-2 Normal T- Full threshold strategy tests at baseline and one additional exam at 3 months for each eligible eye. Spearman, intraclass correlation coefficients (ICCs), and Bland-Altman plots were used to assess the correlation of individual point sensitivities and mean deviation (MD) among three tests.Eighty-eight eyes (44 participants) were included. Average age was 68.1 ± 14.3 years, and 60.7% were male. VisuALL MD was highly correlated between tests (intravisit: r = 0.89, intervisit: r = 0.82; P < 0.001 for both). Bland-Altman analysis showed an average difference in intravisit MD of -0.67 dB (95% confidence interval [CI], -6.04 to 4.71 dB) and -0.15 dB (95% CI, -8.04 to 7.73 dB) for intervisit exams. Eight-five percent of pointwise intravisit ICCs were above 0.75 (range, 0.63 to 0.93), and 65% of pointwise intervisit ICCs were above 0.75 (range, 0.55 to 0.91).VisuALL demonstrated high correlation of MD between tests and good repeatability for individual point sensitivities among three tests in 3 months, except at the points around the blind spot and superiorly.The preliminary reproducibility results for VisuALL are encouraging. Its portable design makes it a potentially useful tool for patients with glaucoma, enabling more frequent assessments both at home and in clinical settings.

  View details for DOI 10.1167/tvst.13.6.14

  View details for PubMedID 38899952

• Oculometric biomarkers of visuomotor deficits in clinically asymptomatic patients with systemic lupus erythematosus undergoing long-term hydroxychloroquine treatment. Frontiers in ophthalmology Berneshawi, A. R., Seyedmadani, K., Goel, R., Anderson, M. R., Tyson, T. L., Akay, Y. M., Akay, M., Leung, L. B., Stone, L. S. 2024; 4: 1354892

  Abstract

  Introduction: This study examines a set of oculomotor measurements, or "oculometric" biomarkers, as potential early indicators of visual and visuomotor deficits due to retinal toxicity in asymptomatic Systemic Lupus Erythematosus (SLE) patients on long-term hydroxychloroquine (HCQ) treatment. The aim is to identify subclinical functional impairments that are otherwise undetectable by standard clinical tests and to link them to structural retinal changes.Methods: We measured oculomotor responses in a cohort of SLE patients on chronic HCQ therapy using a previously established behavioral task and analysis technique. We also examined the relationship between oculometrics, OCT measures of retinal thickness, and standard clinical perimetry measures of visual function in our patient group using Bivariate Pearson Correlation and a Linear Mixed-Effects Model (LMM).Results: Significant visual and visuomotor deficits were found in 12 asymptomatic SLE patients on long-term HCQ therapy compared to a cohort of 17 age-matched healthy controls. Notably, six oculometrics were significantly different. The median initial pursuit acceleration was 22%, steady-state pursuit gain 16%, proportion smooth 7%, and target speed responsiveness 31% lower, while catch-up saccade amplitude was 46% and fixation error 46% larger. Excluding the two patients with diagnosed mild toxicity, four oculometrics, all but fixation error and proportion smooth, remained significantly impaired compared to controls. Across our population of 12 patients (24 retinae), we found that pursuit latency, initial acceleration, steady-state gain, and fixation error were linearly related to retinal thickness even when age was accounted for, while standard measures of clinical function (Mean Deviation and Pattern Standard Deviation) were not.Discussion: Our data show that specific oculometrics are sensitive early biomarkers of functional deficits in SLE patients on HCQ that could be harnessed to assist in the early detection of HCQ-induced retinal toxicity and other visual pathologies, potentially providing early diagnostic value beyond standard visual field and OCT evaluations.

  View details for DOI 10.3389/fopht.2024.1354892

  View details for PubMedID 39104603

• Expert vs. Novice Review of Ophthalmic Data: An Oculography Study of Optic Neuropathies Patwardhan, A., Berneshawi, A., Yu, M., Liao, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023

  View details for Web of Science ID 001053795604029

• Expert vs. Novice: Characterizing Visuo-Motor Behavior During Static Perimetry Interpretation Berneshawi, A., Patwardhan, A., Yu, M., Liao, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023

  View details for Web of Science ID 001053795604039

• Conversion of hepatitis B virus relaxed circular to covalently closed circular DNA is supported in murine cells JHEP REPORTS Wei, L., Cafiero, T. R., Tseng, A., Gertje, H. P., Berneshawi, A., Crossland, N. A., Ploss, A. 2022; 4 (9): 100534

  Abstract

  HBV has a narrow host restriction, with humans and chimpanzees representing the only known natural hosts. The molecular correlates of resistance in species that are commonly used in biomedical research, such as mice, are currently incompletely understood. Expression of human NTCP (hNTCP) in mouse hepatocytes enables HBV entry, but subsequently covalently closed circular (cccDNA) does not form in most murine cells. It is unknown if this blockade in cccDNA formation is due to deficiency in repair of relaxed circular DNA (rcDNA) to cccDNA.Here, we deployed both in vivo and in vitro virological and biochemical approaches to investigate if murine cells contain a complete set of repair factors capable of converting HBV rcDNA to cccDNA.We demonstrate that HBV cccDNA does form in murine cell culture or in mice when recombinant rcDNA without a protein adduct is directly introduced into cells. We further show that the murine orthologues of core components in DNA lagging strand synthesis, required for the repair of rcDNA to cccDNA in human cells, can support this crucial step in the HBV life cycle. It is worth noting that recombinant HBV rcDNA substrates, either without a protein adduct or containing neutravidin to mimic HBV polymerase, were used in our study; it remains unclear if the HBV polymerase removal processes are the same in mouse and human cells.Collectively, our data suggest that the HBV life cycle is blocked post entry and likely before the repair stage in mouse cells, which yields critical insights that will aid in the construction of a mouse model with inbred susceptibility to HBV infection.Hepatitis B virus (HBV) is only known to infect humans and chimpanzees in nature. Mouse models are often used in modeling disease pathogenesis and preclinical research to assess the efficacy and safety of interventions before they are then tested in human participants. However, because mice are not susceptible to HBV infection it is difficult to accurately model human infection (and test potential treatments) in mouse models. Herein, we have shown that mice are able to perform a key step in the HBV life cycle, tightening the net around the possible reason why HBV can not efficiently infect and replicate in mice.

  View details for DOI 10.1016/j.jhepr.2022.100534

  View details for Web of Science ID 000860407000001

  View details for PubMedID 36035363

  View details for PubMedCentralID PMC9403495

• Repeatability and correlation of a virtual reality perimeter with standard automated perimetry in glaucoma patients Chaudhry, A., Berneshawi, A., Liu, J., Shue, A., Chang, D., Kim, J., Chang, R. T. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844401303262

• Correlated Changes in Retinal Thickness and Visuomotor Function in Asymptomatic Hydroxychloroquine Toxicity Patients Leung, L., Hwang, B., Berneshawi, A., Goel, R., Tyson, T., Chang, R. T., Stone, L. S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844437004206

• Feasibility of Glaucoma Home Self Testing Using a Virtual Reality Visual Field Test Combined with Home Tonometry Berneshawi, A., Shue, A., Chang, R. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844401303264