Purpose: Our recent publication used optical coherence tomography (OCT) to follow thinning of the retinal ganglion cell layer (GCL) in central retinal artery occlusion (CRAO). Thinning of the inner layers also occurs in patients with branch retinal artery occlusion (BRAO). The mechanism for such thinning may be partially due to proteolysis by a calcium-activated protease called calpain. Calpain inhibitor SNJ-1945 ameliorated the proteolysis in a past series of model experiments. The purposes of the present retrospective study were to: 1) use segmentation analysis of OCT images to follow the loss of retinal layers in BRAO compared to CRAO patients, and 2) predict the number of patients and days of observation needed for a clinical trial of a calpain inhibitor against BRAO.
Methods: A retrospective, case control study was conducted by computer-aided search in a medical records database for BRAO (ICD10 Code H34.239) with at least one OCT procedure (CPT: 92134). Non-proliferative, co-morbid eye diseases were allowed in the patient data base, and manual correction of auto-segmentation errors was performed. GCL thickness changes were followed over time and Cohen-d/sample size statistics were used to predict minimal patients needed for drug trials.
Results: The thickness of the GCL layer in BRAO decreased rapidly with time as in CRAO, but in more limited quadrants. The data, as fit to a single-phase decay curve, showed that GCL thickness could be used to provide sample size statistics in a clinical trial to test a calpain inhibitor. For example, a 60-day trial with a 60% effective inhibitor would need a minimum of 29 patients.
Conclusions: Using thickness changes in the GCL layer to monitor the efficacy of potential inhibitors against BRAO and CRAO is practical in human trials requiring a reasonable number of patients and relatively short trial period.
Translational Relevance: Measurement of GCL thickness would be a useful indicator of amelioration of BRAO and CRAO progression in a clinical trial of a putative inhibitor.
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| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0279920 | PLOS |
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9815566 | PMC |
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