Glaucoma Clinical Research: Trends in Treatment Strategies and Drug Development

Abstract

Purpose: To investigate the trends and progresses in glaucoma research by searching two major clinical trial registries; clinicaltrials.gov, and Australianclinicaltrials.gov.au.Methods: All clinical trials with glaucoma covered by Clinicaltrials.gov, and Australianclinicaltrials.gov.au starting the study before 1 January 2021 were included. Trials evaluating glaucoma treatment were separated from non-treatment trials and divided into three major categories: “laser treatment,” “surgical treatment,” and “medical treatment.” In the category of “medical treatment,” new compounds and their individual targets were identified and subcategorized according to treatment strategy; intraocular pressure (IOP)-lowering, neuroprotective or vascular. The phase transition success rates were calculated.Results: One-thousand five hundred and thirty-seven trials were identified. Sixty-three percent (n = 971) evaluated glaucoma treatment, of which medical treatment accounted for the largest proportion (53%). The majority of medical trials evaluated IOP-lowering compounds, while trials with neuroprotective or vascular compounds accounted for only 5 and 3%, respectively. Eighty-eight new compounds were identified. Phase I, II, and III transition success rates were 63, 26, and 47%, respectively.Conclusion: The number of clinical trials in glaucoma research has increased significantly over the last 30 years. Among the most recently evaluated compounds, all three main treatment strategies were represented, but clinical trials in neuroprotection and vascular modalities are still sparse. In addition to traditional medicines, dietary supplements and growth factors are assessed for a potential anti-glaucomatous effect. Phase II and III success rates were below previously reported success rates for all diseases and ophthalmology in general. A stricter phenotyping of patients can improve the success rates in glaucoma and ophthalmological research and gain a better understanding of responders and non-responders.

Brain-Derived Neurotrophic Factor-Mediated Neuroprotection in Glaucoma: A Review of Current State of the Art

“…Besides, topical administration of BMD is associated with greater side effects, including hyperemia, discomfort, and hypersensitivity, as compared to other topical anti-glaucoma medications. A selectively higher dropout rate could have skewed the results in the BMD arm as compared to the timolol arm ( Storgaard et al, 2021 ). Unfortunately, this observation is not limited to BMD only.…”

“…Besides that, there have been no substantial evidence of non-IOP lowering medications that could alter the glaucoma progression, and none of them could provide neuroprotection to recover the retinal and neural function in clinical trials ( Lusthaus and Goldberg, 2019 ). An analytical review by Storgaard et al suggests that despite several glaucoma related preclinical and clinical trials in the last 30 years, a successful translations to actual clinical use has not been achieved ( Storgaard et al, 2021 ). The barriers to translate from preclinical into clinical practice may include heterogeneous nature of disease that is difficult to mimic fully in animal models leading to the variability in outcome measures, differences in ocular bioavailability, and the optimal timing of intervention.…”

Designs and Methodologies Used in Landmark Clinical Trials of Glaucoma: Implications for Future Big Data Mining and Actionable Disease Treatment

“…The field of glaucoma has the second largest number of published randomized controlled trials in all of ophthalmology, the majority of which evaluate glaucoma treatments ( 5 , 6 ). Landmark randomized controlled trials have shaped the practice of glaucoma care and are commonly used to teach medical learners the basics of treating patients with suspected or diagnosed glaucomatous optic neuropathy ( 7 – 10 ).…”

Retinal degeneration induced in a mouse model of ischemia–reperfusion injury and its management by pemafibrate treatment

“…12,13 Therefore, various therapeutic approaches have been examined for the prevention and suppression of retinal I/R injury at preclinical stages. 14 Pemafibrate is a selective peroxisome proliferatoractivated receptor α (PPARα) modulator, which was developed and marketed by Kowa Pharmaceuticals as a clinically effective treatment for metabolic diseases, including dyslipidemia. 15,16 Over the past decades, a positive point of view on PPARα modulation-based therapy has been stacked in the central nervous system diseases in terms of the protective and preventive effects.…”