Ikervis and Restasis treatment of DED was effective, as both improved OSS and FBUT. Fluorescein staining as measured by OSS is a well-established method for evaluating the health of the ocular surface and its barrier function; hence, improved staining values would be of particular interest as they indicate improvement in ocular surface integrity. Previous studies have shown that Restasis decreases OSS and improves OSDI, Schirmer’s test, and FBUT 24–27. Similar results have been shown for Ikervis, with significant improvement as early as 1 month after the initiation of treatment 28–30. Our results found no major differences between the improvement in the two groups. High OSS at baseline appeared to result in a greater response to treatment.
The Schirmer’s test with anesthesia is a measure of baseline tear production, whereas the test without anesthesia measures the combination of baseline and reflex tear production as the ocular surface is irritated by the paper strip. Wan et al. hypothesized that the improved OSS, a sign of decreased inflammation and improved ocular surface epithelial quality, results in decreased sensory-driven reflex tear production 24. The authors supported this assertion by demonstrating a significant increase in the score for the Schirmer’s test without local anesthesia along with an improvement in OSS. On the contrary, the patients in the present study had consistently undergone the Schirmer’s test without anesthesia and did not show any improvement. Sall et al. have reported the same findings as the present study 25.
The subgroup and regression analysis showed that patients with severe symptoms (OSDI score > 33) at baseline were the only ones to show significant improvements in symptoms after treatment in both groups. A change in OSDI score by ≥ 10 is considered clinically significant 31. Leonardi et al. reported a significant decrease in OSDI score by 14.4 after 6-months Ikervis use 29. Baudouin et al. demonstrated similar results in their Ikervis study 28, and many studies have shown clinically significant improvements by Restasis 32–34. The OSDI results in our study agree with those in the previous studies for patients with severe symptoms.
Interestingly, we found that Ikervis-treated patients with none or mild symptoms at baseline had a significant increase in symptoms over six months. There were not enough Restasis-treated patients in these subgroups for a similar analysis. Ikervis is known to cause pain upon instillation 28 and the OSDI-questionnaire requires the patients to answer if they have had any ocular discomfort in the last week 18. As the side-effects of Ikervis includes discomfort, this may have confounded the OSDI-results. Patients with few dry eye related complaints at baseline should be warned of a potential increase in symptoms during the initial six months of treatment. Further and larger long-term studies, however, are warranted to draw more certain conclusions.
The tear film is a complex fluid that protects the ocular surface. Tear film instability, a key finding in DED, causes more frequent blinking, which may lead to interference with visual tasks and to visual fatigue. The tear film is restored after a blink, when fluid secretion from the meibomian glands is released onto the ocular surface. The stability of the tear film can be quantified with FBUT, which improved significantly after treatment with both drugs when baseline FBUT was under five seconds. This was seen in previous studies for both drugs 24,26,28. Interestingly, our findings show that Restasis patients had a larger increase in FBUT than Ikervis. The treatment was also more effective at increasing FBUT in males and in younger patients.
The anti-inflammatory effect of CsA is beneficial for treating MGD as it may improve MQ 35–38. In the present study, all patients had MGD to a certain degree, with decreased FBUT and increased MQ and ME, and they were instructed to undergo warming therapy in addition to CsA treatment, although compliance is unknown. MGD is the leading cause of DED and has been associated with increased levels of inflammatory cytokines in tear fluids, such as IL-1, IL-6, IL-8, IL-12, epidermal growth factor, and tumor necrosis factor-alpha 39,40. Of special interest is IL-6, the levels of which differ most greatly between healthy and dry eyes 41,42. CsA can decrease IL-6, which may explain its usefulness for treating DED caused by MGD 43. In our study, both drugs improved FBUT significantly with some superiority to Restasis, whereas Ikervis showed superiority in regards to ME improvement. Hence, both drugs seem to be effective at treating MGD.
Our study has some limitations. A retrospective study design is not ideal for comparing two drugs and therefore offers a lower level of evidence compared to a prospective randomized controlled study. The data for this study was collected over a period of many years, and during this time the operating procedure at the clinic evolved and more data was gradually collected at control visits. As a result, the number of parameters included at six months follow-up is not the same for all the patients, offering less evidence for our results on ME, MQ, and OSDI. The major strength of this study beside sample size is that there is no other comparisons of these two drugs in the scientific literature. Thus, our results offer a unique insight into their efficacies.
In conclusion, our study does not indicate a substantial difference in efficacy between the two drugs as both Restasis and Ikervis caused objective and subjective improvement in DED patients. The severity of DED appears to be a good indicator for therapy response in both groups, with Restasis being more effective at improving FBUT and Ikervis more effective at improving ME.