Tear Film Thickness (TFT) is the Most Sensitive Measure to Capture Differences in the Critical Quality Attributes of a Formulation Using Anterior Segment Optical Coherence Tomography (AS-OCT)

Abstract

Purpose : The purpose of this study was to obtain TFT and menisci measurements on Dutch Belted (DB) rabbit ocular surface post instillation (PI) of cyclosporine ophthalmic emulsion formulations (CsF) with varying viscosity and globule size distribution (GSD).

Methods : A total of 416 experiments were conducted on 16 DB rabbits. Tear variable measurements were obtained using Heidelberg Spectralis^® Eye Explorer (HEYEX) software on the scans captured with AS-OCT. Inter-operator and inter-occasion reproducibility of HEYEX was also established. Five compositionally identical CsF with varying GSD and viscosity, three placebos, 3 lots of Restasis®, Refresh Liquigel® (RL) and sterile water were tested for tear variables like TFT, upper and lower tear film meniscus cross-sectional area (UMA & LMA) immediately after instillation, and at 5, 10, 20, and 40 minutes.

Results : All formulations resulted in immediate increase in the levels of TFT, UMA and LMA. TFT and LMA levels were followed by a sharp decrease within 10 minutes and then a more gradual decrease afterwards. UMA levels were followed by a sharp decrease within 5 minutes. For most formulations, tear variables levels returned to baseline within 20 minutes. The formulation with highest viscosity/similar GSD produced higher TFT at 5 minutes. Similarly, the formulation with highest GSD/similar viscosity produced highest TFT among all CsF at 5 minutes. Formulations with lower GSD/medium viscosity and higher GSD/medium viscosity had higher TFT compared to other CsF at 20 minutes. Placebo with low to high viscosity established a correlation between TFT levels and viscosity. RL and Placebo with highest viscosity had the greatest increase in TFT among all formulations immediately PI. All 3 lots of Restasis exhibited comparable TFT levels at all time points. Water exhibited the lowest TFT. Restasis, CsF and RL exhibited comparable UMA and LMA levels at all time points. Highest GSD formulations gave rise to largest change in all tear variables. Highest viscosity formulations appeared to have the greatest changes to TFT and LMA.

Conclusions : Overall, TFT data revealed that earlier time points within 10 minutes PI correlate well with formulations that vary in GSD and viscosity. TFT appears to be the most sensitive measure to capture differences in GSD and viscosity.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.