Lifitegrast for the Treatment of Dry Eye Disease

Holland, Edward J.; Luchs, Jodi; Karpecki, Paul; Nichols, Kelly K.; Jackson, Mitchell; Sall, Kenneth; Tauber, Joseph; Roy, Monica; Raychaudhuri, Aparna; Shojaei, Ali Asghar

doi:10.1016/j.ophtha.2016.09.025

Cited by 145 publications

(102 citation statements)

References 14 publications

(13 reference statements)

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“…As in other clinical trials of treatments for dry eye disease, the placebo effect was substantial. 13,14 Results from the analysis of the primary outcome (mean change in the OSDI score), prespecified subgroup analyses, and analyses of all the secondary outcomes consistently showed a difference between the active supplement group and the placebo group that was small and not significant.…”

Section: Discussionmentioning

confidence: 94%

n−3 Fatty Acid Supplementation for the Treatment of Dry Eye Disease

Asbell²,

et al. 2018

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BACKGROUND Dry eye disease is a common chronic condition that is characterized by ocular discomfort and visual disturbances that decrease quality of life. Many clinicians recommend the use of supplements of n–3 fatty acids (often called omega-3 fatty acids) to relieve symptoms. METHODS In a multicenter, double-blind clinical trial, we randomly assigned patients with moderate-to-severe dry eye disease to receive a daily oral dose of 3000 mg of fish-derived n–3 eicosapentaenoic and docosahexaenoic acids (active supplement group) or an olive oil placebo (placebo group). The primary outcome was the mean change from baseline in the score on the Ocular Surface Disease Index (OSDI; scores range from 0 to 100, with higher scores indicating greater symptom severity), which was based on the mean of scores obtained at 6 and 12 months. Secondary outcomes included mean changes per eye in the conjunctival staining score (ranging from 0 to 6) and the corneal staining score (ranging from 0 to 15), with higher scores indicating more severe damage to the ocular surface, as well as mean changes in the tear break-up time (seconds between a blink and gaps in the tear film) and the result on Schirmer’s test (length of wetting of paper strips placed on the lower eyelid), with lower values indicating more severe signs. RESULTS A total of 349 patients were assigned to the active supplement group and 186 to the placebo group; the primary analysis included 329 and 170 patients, respectively. The mean change in the OSDI score was not significantly different between the active supplement group and the placebo group (−13.9 points and −12.5 points, respectively; mean difference in change after imputation of missing data, −1.9 points; 95% confidence interval [CI], −5.0 to 1.1; P=0.21). This result was consistent across prespecified subgroups. There were no significant differences between the active supplement group and the placebo group in mean changes from baseline in the conjunctival staining score (mean difference in change, 0.0 points; 95% CI, −0.2 to 0.1), corneal staining score (0.1 point; 95% CI, −0.2 to 0.4), tear break-up time (0.2 seconds; 95% CI, −0.1 to 0.5), and result on Schirmer’s test (0.0 mm; 95% CI, −0.8 to 0.9). At 12 months, the rate of adherence to treatment in the active supplement group was 85.2%, according to the level of n–3 fatty acids in red cells. Rates of adverse events were similar in the two trial groups. CONCLUSIONS Among patients with dry eye disease, those who were randomly assigned to receive supplements containing 3000 mg of n–3 fatty acids for 12 months did not have significantly better outcomes than those who were assigned to receive placebo. (Funded by the National Eye Institute, National Institutes of Health; DREAM ClinicalTrials.gov number, NCT02128763.)

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Section: Discussionmentioning

confidence: 94%

n−3 Fatty Acid Supplementation for the Treatment of Dry Eye Disease

Asbell²,

et al. 2018

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“…Treatments currently available to control inflammation in DED and prevent severe cornea complications include corticosteroids, 6,7 cyclosporine A (CsA), [8][9][10] and lifitegrast (a novel integrin antagonist), 11,12 even though the latter is intended for the treatment of mild-to-moderate DED in patients who are more prone to respond well to artificial tears. 13 Corticosteroids are very effective at controlling inflammation.…”

Section: Introductionmentioning

confidence: 99%

Modulation of Inflammation-Related Genes in the Cornea of a Mouse Model of Dry Eye upon Treatment with Cyclosporine Eye Drops

Daull

Barabino

Feraille³

et al. 2019

Current Eye Research

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Purpose/Aim: Inflammation is recognized as playing an etiological role in dry eye disease. This study aimed to assess the efficacy of various topical cyclosporine A (CsA) formulations on cornea inflammatory markers in a mouse model of dry eye. Material and Methods: Six-to 7-week-old mice treated with scopolamine were housed in a controlled environment room to induce dry eye. Following dry eye confirmation by corneal fluorescein staining (CFS), the mice were treated three times a day with: 0.05%CsA (Restasis, Allergan), 0.1%CsA (Ikervis, Santen), 1%CsA oil solution, and 0.5% loteprednol etabonate (LE, Lotemax, Baush+Lomb), or left untreated. Aqueous tear production and CFS scores were assessed during the treatment period, and corneas were collected to measure the expression profile of a selection of inflammatory genes. Results: After 7 days of treatment, the CFS scores were reduced by 21%, 31%, and 44% with 0.05%CsA, 0.1%CsA, and 1%CsA eye drops, respectively. By contrast, 0.5% LE did not decrease corneal fluorescein staining at day 10. A statistically significant dose-dependent CFS reduction was observed only between the 0.05% and 1%CsA formulations. The gene expression profiles indicated that 12, 18, 17 genes were downregulated by 0.05%CsA, 0.1%CsA, 1%CsA, respectively. Among them, the genes significantly downregulated were: IL1A, IL1R1, and TLR4 with 0.05%CsA; H2-Eb1, IL1A, IL1B, IL1RN, IL6, TGFB2, TGFB3, TLR2, TLR3, and TLR4 with 0.1%CsA; IL1B, IL6, TGFB3, and TLR4 with 1%CsA. TGFB1 and TGFBR1 were the only genes upregulated in all groups, but only TGFB1 upregulation reached significance. IL6RA was significantly upregulated by 0.05%CsA. Conclusions: This study indicates that the three CsA formulations effectively modulated TLR4, TGFβ1, IL1, and IL6 pathways to reduce corneal epithelium lesions in a mouse model of severe dry eye. The study also suggests that the different anti-inflammatory eye drops modulated inflammatory genes in a slightly different manner. ARTICLE HISTORY

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“…In a study by Gürdal et al, Cyclosporine A 0.05% was shown to significantly decrease MMP-9 expression in conjunctival epithelial cells of thyroid orbitopathy patients with dry eye syndrome [46]. Lifitegrast 5% (Xiidra; Shire, Lexington, MA) is a more recently available ophthalmic drop that has been shown to be effective in the treatment of the signs and symptoms of dry eye disease [47,48]. Lifitegrast works as a lymphocyte function-associated antigen-1 (LFA-1) antagonist that blocks binding of intercellular adhesion molecule-1 to LFA-1, which facilitates cellmediated inflammation associated with DED, including honing dendritic cells to T cells and subsequent T cell activation, differentiation, migration, retention and expression on the ocular surface [49].…”

Section: Discussionmentioning

confidence: 99%

Association of Ramadan daytime fasting with ocular surface inflammation and dry eye

et al. 2019

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Purpose Despite the widespread practice of fasting, there are no studies looking at ocular surface inflammation, specifically matrix metalloproteinase 9 (MMP-9) testing, during fasting. In this prospective study, we wanted to evaluate the effect of Ramadan fasting on the level of tear film MMP-9 as well as other standard indicators of dry eye disease. Methods Forty healthy patients without history of ocular disease were tested before and toward the end of Ramadan. Each patient was assessed at each timepoint for tear film MMP-9 positivity as measured by a commercially available test (InflammaDry; Quidel Corp., San Diego, CA, USA) which detects MMP-9 levels of more than 40 ng/ml. Ocular surface disease index (OSDI) scores, tear breakup time (TBUT), Schirmer I test (S1T) and corneal fluorescein staining (CFS) were also evaluated at each timepoint. Results InflammaDry was positive in 10 patients (25%) prior to Ramadan and 21 patients (52.5%) during Ramadan fasting, and this change was statistically significant (p = 0.02). Mean TBUT decreased from 7 s prior to Ramadan to 5.3 s during Ramadan fasting, and this change was statistically significant (p = 0.01). OSDI, CFS and S1T did not show any statistically significant changes (p [ 0.05 for all). Conclusion Ramadan fasting has a significant impact on TBUT and ocular surface inflammation detected by Inflamma Dry testing. Patients who suffer from dry eye disease and those who develop symptoms during Ramadan are advised to consult with a physician before or during Ramadan fasting.

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Lifitegrast for the Treatment of Dry Eye Disease

Abstract: Lifitegrast significantly improved symptoms of eye dryness, as measured by EDS, versus placebo in participants with DED. Improvement in EDS was observed as early as day 14. Lifitegrast appeared well tolerated.

Cited by 145 publications

References 14 publications

n−3 Fatty Acid Supplementation for the Treatment of Dry Eye Disease

n−3 Fatty Acid Supplementation for the Treatment of Dry Eye Disease

Modulation of Inflammation-Related Genes in the Cornea of a Mouse Model of Dry Eye upon Treatment with Cyclosporine Eye Drops

Association of Ramadan daytime fasting with ocular surface inflammation and dry eye

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