First Diquafosol Treatment for Dry Eye: 10-Year Follow-Up

To the Editor:

Since dry eye is a chronic symptomatic ocular surface disease, patients have to use eye drops for a long time. There have been limited reports on the long-term follow-up of continuous dry eye treatment. The long-term follow-up outcomes of topical cyclosporine were reported in 2 studies.^1,2 Ten years ago, a 3% diquafosol sodium ophthalmic solution (Diquas ophthalmic solution 3%; Santen Pharmaceutical Co, Osaka, Japan) was launched for dry eye treatment in Japan, where cyclosporine is not an approved treatment for dry eye. Diquafosol stimulates tear fluid and mucin secretion on the ocular surface, thus alleviating dry eyes.³ Shortly after its commercialization and clinical in early 2011, we reported that the short-term clinical results of diquafosol for 6 months produced significant subjective and objective improvements in 15 aqueous tear-deficient dry eyes.⁴ Herein, we discussed the first cohort of dry eye patients reexamined 1 decade after diquafosol treatment initiation.

Of the 15 patients, 7 were available for examination with an average follow-up duration of 10 years (122.3 ± 1.5 months) from March to August 2021. The total corneal staining, conjunctival staining, and symptom scores improved during the 10-year follow-up visit in all patients (Supplementary Digital Content Figure 1A and 1B, http://links. lww.com/APJO/A138). The previous study results were successfully maintained.⁴ The total corneal and conjunctival staining scores improved from 4.1 ± 1.8 and 5.3 ± 0.7 at baseline to 1.1 ± 1.1 and 3.7± 1.7 after 6 months.⁴ Considering the influence of cataract progression in this population (average age of 68 years during the last visit), only ocular symptoms were assessed. The symptoms improved from 5.7 ± 0.5 at baseline to 1.6 ± 0.5 during the 10-year follow-up. In contrast, no remarkable change was observed in the breakup time (BUT), Schirmer test, or central corneal staining score. Although BUT improvement was observed after 6 months in the previous study,⁴ this was unlikely at the 10-year visit. All subjects were not examined at the same time of the day and season between the 2-time points. The indoor environment of the examination room was mostly stable; however, the exact degree of temperature/humidity might differ, and these data were not recorded. Along with the very small number of patients in this case series, these factors may partly contribute to the BUT results of this study. The improvement in the corneal and conjunctival staining scores was possibly caused by the improved ocular surface wettability due to increased tear fluid and mucin secretion. According to a previous study on rats,⁵ there was no significant age-related decrease in P2Y2 receptor expression on rat ocular surface tissue. The clinical efficacy of 10-year diquafosol treatment in elderly patients in this study may suggest the maintenance of P2Y2 receptor expression on the ocular surface. Further investigation is needed to clarify this.

During the initial 6-month study period,⁴ the patients were instructed to apply only diquafosol 6 times daily on both eyes. After the initial study, all patients used diquafosol only. Four of the 7 patients complied with the frequency of diquafosol application (6 times daily). Although patients were not strictly instructed to timely record the usage, they reported consistency in usage across all seasons. Using nonpreserved artificial tear eye drops was not prohibited after the initial 6-month study period. However, none of the patients reportedly used artificial tear eye drops. No systemic and topical side effects were noted during the 10-year follow-up period.

According to a recent web survey conducted in Japan, the prevalence of ophthalmic follow-up discontinuation among dry eye patients was 67%, which was considerably higher than that of patients with other diseases, such as diabetes mellitus (11%) and psychiatric disorders (53%).⁶ Although the first 10 years of the diquafosol treatment series had weaknesses, such as small sample size, retrospective study design, and performance in a university hospital setting, this review of 7 dry eye patients suggests the sustained effects of continuous diquafosol treatment after a 10-year follow-up. Dry eye is generally not vision-threatening; however, regarding the quality of vision and life, long-term continuous monitoring for dry eye is important, as in other ocular conditions, such as glaucoma or medical retina, where long-term 10-year outcomes are reported.