Abstract
Purpose :
Cyclosporine and punctal plugs are used for the treatment of dry eye disease (DED) to increase tear production and tear conservation, respectively. OTX-CSI, a cyclosporine intracanalicular insert, combines the two modalities into a single treatment, and is designed to provide sustained release cyclosporine along with punctal occlusion. The objective of this study was to investigate the pharmacokinetics of cyclosporine drug released from OTX-CSI in a dry eye model following administration in beagle dogs.
Methods :
Dry eye was surgically induced in the right eye of 12 beagle dogs by removal of lacrimal glands while the left eye was untreated (healthy). Ten days after surgery, OTX-CSI was administered in the canaliculus of both eyes on Day 0. Schirmer tears test were performed in both eyes pre-surgery (baseline prior to surgery on Day -10), post-surgery (Day -3, -2 and -1) and post-insertion of OTX-CSI (Days 11, 20 and 29) to monitor tear production. Tear fluid samples were collected using 10 mm Schirmer test strips at 3 hours, 1, 7, 14 and 28 days post-insertion and analyzed for cyclosporine concentrations by liquid chromatography tandem mass spectrometry.
Results :
Mean Schirmer Tear Test Score was higher in healthy eyes at all timepoints post-baseline compared to dry eyes and was sustained through Day 29 showing successful induction of dry eye model (Figure 1). Mean tear fluid cyclosporine concentrations in the dry eye group were generally higher compared to concentrations in healthy eyes at most time points (Table 1) likely due to less dilution of the cyclosporine on the ocular surface with the reduced tear fluid production of surgically induced dry eyes. OTX-CSI was well tolerated and not associated with any substantial ocular findings and had no adverse effects on general, non-ocular health.
Conclusions :
OTX-CSI successfully released cyclosporine into the tear fluid of surgically induced dry eyes of beagle dogs as demonstrated by cyclosporine concentrations greater than or equal to concentrations in healthy eyes. The reduction in tear fluid production (typically seen in dry eye subjects) does not appear to inhibit transport of cyclosporine to the tear fluid in beagle dry eyes. The insert is currently being evaluated for efficacy and safety in a Phase 2, randomized, masked, vehicle-controlled, multicenter clinical trial in subjects with dry eye (NCT04362670).
This is a 2021 ARVO Annual Meeting abstract.