Refrigeration reduces instillation discomfort of a 0.09% cyclosporine A solution.

Abstract

Significance: Topical cyclosporine A (CsA) for the treatment of dry eye disease is often associated with instillation discomfort, which may negatively influence patient adherence to therapy. This study found that refrigerating topical CsA reduced instillation discomfort compared with instillation of warm CsA. Thus, refrigerating CsA prior to instillation may improve patient experience when using CsA to manage dry eye disease.

Purpose: This study aimed to quantify instillation discomfort associated with cold or warm instillation of a 0.09% CsA.

Methods: Forty participants with symptomatic aqueous deficient dry eye were enrolled. A drop of cold (4°C) CsA was instilled in one eye, and a drop of warm (23°C) CsA was instilled in the other eye. The order and eye receiving the cold drop were randomized. Participants rated the discomfort of each eye (0, no discomfort; 10, maximal discomfort) prior to drop instillation, immediately post-instillation, and at each subsequent minute for 10 minutes. Area under the curve was used to quantify cumulative discomfort.

Results: Forty participants (39.6 ± 18.9 years old, 82% female) completed the study. A majority of participants (n = 24, 60%) experienced reduced cumulative discomfort with cold CsA, whereas the remainder experienced minimal difference (n = 10, 25%) or increased cumulative discomfort (n = 6, 15%). For those with reduced discomfort (n = 24), cumulative discomfort associated with cold instillation (median, 11.5 [2.2, 20.0]) was significantly lower (p<0.01) than cumulative discomfort associated with warm instillation (median, 17.5 [11.2, 32.2]). Cold instillation was associated with a median reduction of 1 discomfort point immediately post-instillation and at all subsequent time points (all p≤0.04, but not significant at t = 10), compared with warm instillation.

Conclusions: Up to 60% of participants found that cold instillation of CsA solution induced less discomfort than warm instillation, lasting up to 9 minutes post-instillation. In contrast, although 15% of participants found reduced discomfort with warm instillation, the magnitude of discomfort associated with warm instillation was not significantly different than cold instillation.