Gala Beykin

All Publications

• Phase I NT-501 Ciliary Neurotrophic Factor Implant Trial for Primary Open-Angle Glaucoma: Safety, Neuroprotection, and Neuroenhancement. Ophthalmology science Goldberg, J. L., Beykin, G., Satterfield, K. R., Nunez, M., Lam, B. L., Albini, T. A. 2023; 3 (3): 100298

  Abstract

  Purpose: To assess the safety and efficacy of a ciliary neurotrophic factor (CNTF) intraocular implant on neuroprotection and neuroenhancement in glaucoma.Design: Open-label, prospective, phase I clinical trial.Participants: A total of 11 participants were diagnosed with primary open-angle glaucoma (POAG). One eye of each patient was assigned as the study (implant) eye.Methods: The study eye was implanted with a high-dose CNTF-secreting NT-501 implant, whereas the other eye served as a control. All patients were followed up for 18 months. Analysis was limited to descriptive statistics.Main Outcome Measures: Primary outcome was safety through 18 months after implantation assessed by serial eye examinations, structural and functional testing, and adverse events (AEs) recording. Parameters measured included visual acuity (VA), Humphrey visual field (HVF), pattern electroretinogram, scanning laser polarimetry with variable corneal compensation (GDx VCC), and OCT. These parameters were also used for secondary analysis of efficacy outcome.Results: All NT-501 implants were well tolerated with no serious AEs associated with the implant. The majority of AEs were related to the implant placement procedure and were resolved by 12 weeks after surgery. Foreign-body sensation was the most commonly reported AE and was self-limited to the postoperative period. The most common implant-related AE was pupil miosis; no patients underwent explant. Visual acuity and contrast sensitivity decreased more in fellow eyes than in study eyes (VA,-5.82 vs.-0.82 letters; and contrast sensitivity,-1.82 vs.-0.37 letters, for fellow vs. study eyes, respectively). The median HVF visual field index and mean deviation measurements worsened (decreased) in fellow eyes (-13.0%,-3.9 dB) and improved (increased) in study eyes (2.7%, 1.2 dB). Implanted eyes showed an increase in retinal nerve fiber layer thickness measured by OCT and by GDx VCC (OCT, 2.66 mum vs. 10.16 mum; and GDx VCC, 1.58mumvs. 8.36mum in fellow vs. study eyes, respectively).Conclusions: The NT-501 CNTF implant was safe and well tolerated in eyes with POAG. Eyes with the implant demonstrated both structural and functional improvements suggesting biological activity, supporting the premise for a randomized phase II clinical trial of single and dual NT-501 CNTF implants in patients with POAG, which is now underway.Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

  View details for DOI 10.1016/j.xops.2023.100298

  View details for PubMedID 37197702

• Corrigendum to Phase 1b Randomized Controlled Study of Short Course Topical Recombinant Human Nerve Growth Factor (rhNGF) for Neuroenhancement in Glaucoma: Safety, Tolerability, and Efficacy Measure Outcomes. Am J Ophthalmol 2022;234:223-234. American journal of ophthalmology Beykin, G., Stell, L., Halim, M. S., Nunez, M., Popova, L., Nguyen, B. T., Groth, S. L., Dennis, A., Li, Z., Atkins, M., Khavari, T., Wang, S. Y., Chang, R., Fisher, A. C., Sepah, Y. J., Goldberg, J. L. 2022

  View details for DOI 10.1016/j.ajo.2022.07.018

  View details for PubMedID 35977854

• Structural and Metabolic Imaging after Short-term Use of the Balance Goggles System in Glaucoma Patients: A Pilot Study. Journal of glaucoma Sun, M. T., Beykin, G., Lee, W. S., Sun, Y., Chang, R., Nunez, M., Li, K. Z., Knasel, C., Rich, C., Goldberg, J. L. 2022

  Abstract

  Short-term use of the Balance Goggles System in glaucoma patients was not associated with observable changes in conventional OCT imaging but metabolic imaging using peripapillary flavoprotein fluorescence may represent a useful adjuctive investigation.To determine whether the intraocular pressure (IOP)-lowering effects of the Balance Goggles System (BGS) are accompanied by changes in retinal thickness measured by ocular coherence tomography, retinal vascular density measured by OCT-angiography, or novel peripapillary metabolic profiling using flavoprotein fluorescence (FPF) measured by a fundus camera.Prospective comparative case-series.8 eyes from 8 patients with open-angle glaucoma ranging from mild to severe.In this prospective, single-center, open-label, non-randomized, single-arm study patients received a baseline evaluation including retinal imaging, then one hour of negative pressure application through the BGS, followed by repeat retinal imaging. Participants then used the BGS at home for 1 month and underwent a repeat evaluation at the conclusion of the trial.Changes in nerve fiber layer thickness, OCTA vascular parameters and FPF scores.Mean baseline IOP was 18.0±3.1 mmHg and there was no significant change in IOP at follow-up. At 1 month compared to baseline, there was a statistically significant improvement in FPF optic nerve head rim scores (12.7±11.6 to 10.5±7.5; P=0.04). Additionally, there was there was a trend towards an increase in RNFL thickness after 1 month (69.5±14.2 to 72.0±13.7; P=0.1), but there were no statistically significant differences observable with any of the OCTA vascular parameters either at 1 hour or after 1 month.There were no significant changes observable using conventional OCT imaging following short-term use of the BGS, although metabolic imaging using FPF may be a useful potential biomarker to complement existing investigations. Additional studies are warranted to further investigate these changes.

  View details for DOI 10.1097/IJG.0000000000002066

  View details for PubMedID 35696700

• Repeatability of swept-source optical coherence tomography angiography (SS-OCTA) metrics in healthy and glaucomatous eyes Manivannan, N., Lee, G. C., Callan, T., Sandhoefner, B., Sung, K., Beykin, G., Trang, K., Lai, G., Wollstein, G., Ishikawa, H., Zambrano, R., Ede, E., Leung, C., Goldberg, J. L., Schuman, J. S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844437002007

• Repeatability of metrics from swept-source optical coherence tomography angiography (SS-OCTA) in normal and glaucomatous eyes Durbin, M., Beykin, G., Callan, T., Trang, K., Michalec, G., Wollstein, G., Ishikawa, H., Sandhoefner, B., Zambrano, R., Lee, G., Ede, E., Leung, C., Goldberg, J. L., Schuman, J. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021

  View details for Web of Science ID 000720324200027

• Phase 1b randomized controlled study of short course topical recombinant human nerve growth factor (rhNGF) for neuroenhancement in glaucoma: safety, tolerability and efficacy measure outcomes. American journal of ophthalmology Gala, B., Laurel, S., Sohail, H. M., Mariana, N., Lilia, P., Bac T, N., Sylvia L, G., Amy, D., Zhongqiu, L., Melissa, A., Tom, K., Sophia Y, W., Robert, C., Ann C, F., Yasir J, S., Jeffrey L, G. 2021

  Abstract

  No approved therapies directly target retinal ganglion cells (RGCs) for neuroprotection or neuroenhancement in glaucoma. Recombinant human nerve growth factor (rhNGF) has been shown to promote RGC survival and function in animal models of optic neuropathy. Here we evaluate safety, tolerability, and efficacy of short-term, high-dose rhNGF eye drops versus placebo in a cohort of glaucoma patients.This study is a single-center, randomized, double-masked, vehicle-controlled, parallel group study designed to assess safety and tolerability as well as short-term neuroenhancement of structure and function (Clinicaltrials.gov NCT02855450). Sixty open-angle glaucoma patients were randomized 40:20 to receive either 180 μg/ml rhNGF or vehicle control eye drops in both eyes, three times daily for 8 weeks, with a 24-week post-treatment follow-up. One eye was officially selected as the study eye, although both eyes were studied and dosed. Primary endpoints were safety, as assessed through adverse events, and tolerability, as assessed through patient reported outcomes. Secondary outcome measures included best corrected visual acuity (BCVA), Humphrey visual field (HVF), electroretinogram (ERG), and optical coherence tomography (OCT) of retinal nerve fiber layer (RNFL) thickness at baseline, after 8 weeks of treatment, and at 4 and 24 weeks after treatment (12- and 32-weeks total).Of the 60 randomized subjects, 23 were female (38%) and the average age was 66.1 years. Through week 32, there were no treatment-related serious adverse events, including no unexpectedly severe progression of optic neuropathy, no adverse events affecting ocular function or pressure, and no drug-related systemic toxicity. Topical high-dose rhNGF was tolerated well, with low level of symptom burden mainly eliciting periocular ache (in 52% of treated, 5% of placebo) and only 3 patients (7.5%) discontinuing treatment due to discomfort, out of whom 1 patient (2.5%) prematurely withdrawing from the study. There were no statistically significant differences in global indices of HVF, and no meaningful differences in total, quadrant, or clock-hour mean RNFL thickness between the groups, although both of these function and structure measures showed non-significant trends towards significance in favor of rhNGF. Real-world participant data was used to generate an estimate of cohort size needed to power subsequent studies.rhNGF is safe and tolerable in a topical 180 μg/ml formulation. Although no statistically significant short-term neuroenhancement was detected in this trial, given the strong effects of NGF in preclinical models and trends detected in this study, analysis for efficacy in a neuroprotection trial is warranted.

  View details for DOI 10.1016/j.ajo.2021.11.002

  View details for PubMedID 34780798

• Discovery and clinical translation of novel glaucoma biomarkers. Progress in retinal and eye research Beykin, G., Norcia, A. M., Srinivasan, V. J., Dubra, A., Goldberg, J. L. 2020: 100875

  Abstract

  Glaucoma and other optic neuropathies are characterized by progressive dysfunction and loss of retinal ganglion cells and their axons. Given the high prevalence of glaucoma-related blindness and the availability of treatment options, improving the diagnosis and precise monitoring of progression in these conditions is paramount. Here we review recent progress in the development of novel biomarkers for glaucoma in the context of disease pathophysiology and we propose future steps for the field, including integration of exploratory biomarker outcomes into prospective therapeutic trials. We anticipate that, when validated, some of the novel glaucoma biomarkers discussed here will prove useful for clinical diagnosis and prediction of progression, as well as monitoring of clinical responses to standard and investigational therapies.

  View details for DOI 10.1016/j.preteyeres.2020.100875

  View details for PubMedID 32659431

• An Open-Label Phase Ib Study to Evaluate Retinal Imaging After Short-term Use of the Balance Goggles System (BGS) in Patients with Glaucoma Li, Z., Knasel, C., Nunez, M., Beykin, G., Goldstein, A., Fisher, A. C., Singh, K., Sun, Y., Chang, R. T., Lee, W., Goldberg, J. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020

  View details for Web of Science ID 000554528303047

• Molecular Biomarkers for Glaucoma. Current ophthalmology reports Beykin, G., Goldberg, J. L. 2019; 7 (3): 171–76

  Abstract

  Purpose of review: This article summarizes the current studies on molecular biomarkers with potential implications in diagnosis, prognosis, and response to treatment in patients with glaucoma.Recent findings: Important advances have occurred in the understanding of the pathogenesis of glaucomatous neurodegeneration. Protein biomarkers associated with inflammatory, neurodegenerative, and other molecular pathways have been described in glaucoma patients in tear film, aqueous fluid, vitreous fluid, and serum, however, we are still far from having a clear picture of the whole molecular network that relates to the disease and its implications in clinical use.Summary: Although more studies are needed, current and emerging molecular biomarkers candidates in glaucoma may eventually transition into clinical use and contribute to outline the concept of precision medicine and precision health in glaucoma.

  View details for DOI 10.1007/s40135-019-00213-0

  View details for PubMedID 33133776