Development of a novel protocol to evaluate contact-lens related ocular surface health on marmosets (Callithrix jacchus)

Abstract

Contact lens wear affects the ocular surface and can cause contact lens-induced dry eye (CLIDE). The purpose of this study was bifold: (1) to develop a novel protocol to assess the ocular surface in a non-human primate (NHP) model, the common marmoset (Callithrix jacchus), and (2) to characterize central corneal thickness (CCT), tear osmolarity, blink rate and tear meniscus height (TMH) longitudinally, in untreated marmosets (controls) compared to animals treated with contact lenses (CL). Longitudinal changes in CCT (N = 10 control; N = 10 treated with contact lenses, CL-treated), osmolarity (N = 4 control; N = 6 CL-treated), blink rate (N = 8 control; N = 10 CL-treated) and TMH (N = 8 control; N = 6 CL-treated) were assessed using high frequency A-scan ultrasound, the I-PEN Vet Tear Osmolarity System, a video recording system (745 frames/minute) and Image J respectively, from 70 days to 224 days (5 months) at approx. 9am, and again after 9hrs of CL wear (methafilcon A, 55% water content; Capricornia, Australia) after every 4 weeks of contact lens wear for a total of 22 weeks of treatment. Repeated measures ANOVA was used to compare eyes over time and student t-test was used to compare treated to control eyes at each time point. At baseline, untreated marmosets had a CCT (mean ± SD) of 0.31 ± 0.01 mm, tear osmolarity 311.67 ± 11.48 mOsms/L, blink rate 1.83 ± 1.79 blinks per minute (bpm) and TMH 0.07 ± 0.02 arbitrary units (au), all of which remained stable over 5 months, except blink rate that increased to 5.32 ± 1.58 bpm (p < 0.01) after 5 months. In CL-treated marmosets, however, CCT progressively increased with CL wear (baseline: 0.30 ± 0.01 mm; 5 months: 0.31 ± 0.02 mm, p < 0.05), while osmolarity decreased after 2 and 3 months of CL wear (baseline: 316.11 ± 13.63; 2 months: 302.63 ± 11.27, p < 0.05; 3 months: 302.92 ± 14.58, p < 0.05). The decrease in osmolarity occurred in parallel to an increase in blink rate (baseline: 0.98 ± 1.18 bpm; 2 months: 3.46 ± 3.04 bpm, p < 0.05; 3 months: 3.73 ± 1.50 bpm, p < 0.001). TMH decreased during the third month of CL wear (baseline: 0.06 ± 0.00 au; 3 months: 0.05 ± 0.01 au, p < 0.05), and increased after 4 months (0.08 ± 0.01 au, p < 0.05). As TMH decreased, tear osmolarity increased in both control (R = -0.66, p < 0.05) and CL-treated marmosets (R = -0.64, p < 0.05). The results suggest that marmosets treated with CL for 5 months experienced an increase in blink rate, CCT and TMH, along with a decrease in osmolarity within the first few months of CL treatment that differed from the unaffected stable ocular surface findings observed untreated animals. We hypothesize that CL wear in marmosets might induce an increased blink rate and TMH, in turn delaying the development of hyperosmolarity. These findings confirm that the marmoset is a good novel animal model for ocular surface research for the assessment of novel contact lens materials aimed to alleviate CLIDE.

Keywords: Blink rate; Contact lens; Corneal thickness; Dry eye; Osmolarity; Tear meniscus.