Prevalence of dry eye diseases in metabolic dysregulated versus age-matched normal non-human primates

Abstract

Purpose : Dry eye disease (DED) is one of the most frequently encountered ocular disorders that co-existed with comorbidities including diabetes. However, limited availability of translational animal model has dampened investigation of its etiology, pathogenesis and development of effective therapies. This study was conducted to assess the prevalence of DED in aged and metabolically dysregulated cohorts of non-human primates (NHPs) with the aim that a human-like animal model with multifactorial etiologies will be developed.

Methods : KBI currently has over 3000 male cynomolguses with metabolic diseases caused by either HFD feeding or natural aging. Metabolic disease was monitored longitudinally using body weight, intravenous glucose tolerance tests (ivGTT), blood pressure and clinical chemistry. Monkeys were determined to have diabetes mellitus if the following requirements were met: fasting glucose level > 100mg/dL, glucose disposal rate < 1.3% and hemoglobin A1c test (HbA1c) > 5%. Additionally, ivGTT results provided more guidelines for identifying diabetic cynomolgus monkeys.
For the DED assessment, the monkeys were anesthetized with IM ketamine (5-10mg/kg) and xylazine (0.5-1mg/kg). DED was assessed using Schirmer’s I test (SIT), tear break up time (TBUT) and cornea fluorescein staining (CFS). Monkeys whose test results matched two of the following conditions were characterized with severe DED: SIT≤3mm or TBUT≤3sec or CFS score≥3. Monkeys with moderate DED matched two of the following conditions: SIT=3-10mm or TBUT=3-10sec or CFS score=2-3.

Results : As a progress report thus far, 87 monkeys of ages 15.3±0.3 years, of which 48 are diabetic and 39 are age matched non-diabetic, have been enrolled in the current study. Based on SIT, TBUT and CFS scores, among the 96 eyes assessed in diabetic monkeys, 11% and 58% were characterized as severe and moderate dry eye, respectively. From the 78 eyes examined in non-diabetic monkeys, 8% and 47% were characterized as severe and moderate dry eye, respectively. Based on TBUT (p<0.05), there were significantly more eyes categorized as severe dry eye in diabetic monkeys than in non-diabetic monkeys.

Conclusions : Even though DED symptoms developed spontaneously in both KBI diabetic and non-diabetic cynomolgus colonies, the prevalence of DED in diabetic monkeys was slightly greater than that of non-diabetic monkeys.

This is a 2020 ARVO Annual Meeting abstract.