A comparative study of efficacy, safety and quality of life with lifitegrast 5 percentage and cyclosporine 0.05 percentage eye drops in moderate to severe dry eye disease.

Dry Eye Disease (DED) is a complex, multifactorial condition affecting the ocular surface, characterized by an imbalance in tear film homeostasis. It involves key pathological mechanisms including tear film instability, ocular surface inflammation and damage, increased tear osmolarity and neurosensory dysfunction.

DED is emerging as an important cause of ocular morbidity, with its worldwide prevalence being 29.5%and 17.7% in India.The prevalence of DED is high in women and individuals aged 50 and above. However, in recent years, there has been an increase in the prevalence of DED among young adults, which can be attributed to the widespread use of electronic devices in day-to-day life. The long-term use of contact lenses has also led to the risk of the development of DED.

Patients with DED report redness, burning and stinging, ocular dryness, photophobia, foreign body sensation, grittiness, and visual disturbance, all of which significantly affect quality of life, such that up to 34 % of sufferers report impairment in daily activities. School going children, with DED, appear to experience a similar profile of symptoms to adults and the impact of DED on quality of life is considerable, with effects on presenteeism, concentration, and performance at school and other activities, including reading and playing.

The diagnosis of DED is made by using clinical tests, along with the signs and symptoms of DED. According to the International Dre Eye Workshop (DEWS), sponsored by the Tear Film and Ocular Surface (TFOS) Society (TFOS DEWS II), diagnostic criteria for dry eye disease includes ocular surface index (OSDI), tear film breakup time (TFBUT/TBUT), Schirmer’s tear test (STT), corneal fluorescein staining (CFS) and conjunctival redness.

The management and treatment of DED includes a spectrum of interventions, like patient education, environmental changes, dietary and lifestyle modifications, tear retention, replacement and stimulation approaches, ocular surface protection, topical and/or systemic anti-inflammatory medications, and in more severe cases, surgical intervention.

Lifestyle modifications and lubricants are the common, first line treatment for mild cases of DED. Tear supplements also known as artificial tears (ATs), like polyethylene glycol, are approved by the Food and Drug Administration (FDA), for the temporary relief of symptoms caused by DED. They primarily act as lubricants; hence they only provide quick symptomatic relief but fail to address the root cause of the condition. Also, many formulations of artificial tears contain preservatives, which can lead to ocular damage or can trigger allergic, toxic or inflammatory responses, with their prolonged use.

Therefore, in more severe forms of disease, topical anti-inflammatory drugs like NSAIDS, corticosteroids and cyclosporine is required which breaks the vicious cycle of inflammation in DED. NSAIDs drops like diclofenac sodium and ketorolac tromethamine help to alleviate the inflammation caused by DED. The long-term use of corticosteroids like loteprednol etabonate can increase the risk of side effects like glaucoma, cataract and opportunistic infections.

Cyclosporine 0.05% eye drops has been approved by FDA as topical anti-inflammatory medication for DED, which acts by interfering with the growth and activity of T cells. It enters the T cells and binds with cyclophilin. This cyclosporine –cyclophilin complex blocks the action of calcineurin, thereby inhibiting the release of proinflammatory mediators.

Lifitegrast 5% eye drops was approved by the FDA in 2016, but it was approved by CDSCO in India in 2023. It targets the Lymphocyte function associated antigen –1(LFAA-1). It reduces the activation of T cells, by inhibiting the interaction between LFAA-1 and InterCellular Adhesion Molecule 1(ICAM-1). Thus, preventing the T cell mediated inflammation and is the first FDA approved medication for treatment of both signs and symptoms of DED.

Hence this study primarily aims to compare the efficacy, safety and quality of life with lifitigrast 5% eye drops and cyclosporine 0.05% eye drops, in moderate to severe dry eye disease.

AIM

To evaluate and compare the efficacy, safety, and quality of life with Lifitegrast 5% and Cyclosporine 0.05% eye drops, in moderate to severe DED.

OBJECTIVES:

1.        To assess the efficacy of Lifitegrast 5% and Cyclosporine 0.05% eyedrops in DED, by observing Tear film breakup time (TBUT), Schirmers Test -1 (ST- 1) and Corneal Fluorescein Staining (CFS) at baseline, 2, 6   and 12 weeks.

2.        To assess the safety of Lifitegrast 5% and Cyclosporine 0.05% eyedrops in DED by assessing ADR monitoring and ophthalmic examination throughout the study.

3.        To assess the quality of life with Lifitegrast 5% and cyclosporine 0.05% eyedrops in DED, by assessing the Ocular Surface Disease Index (OSDI), at baseline and 12 weeks.

DRUG TREATMENT

The eligible patients after the screening will be randomly allocated to two treatment groups. Each study group will minimally have 35 patients and will receive one of the following treatments topically for 12 weeks.

Group A: Cyclosporine eye drops 0.05% BD

Group B: Lifitigrast eye drops 5% BD

Available commercial preparation (same brand) of the drugs will be used.

Statistical analysis:

Data will be expressed as Mean ± SEM unless specified otherwise. Intragroup and intergroup statistical analysis will be done in all the groups. Intragroup analysis for repeated measures will be done using ANOVA for parametric data and Friedman’s test for non-parametric data. Intergroup analysis will be done using an unpaired t-test for parametric data and Mann Whitney U test for non-parametric data. Categorical data like the incidence of adverse events in all the groups will be analyzed using the Chi-square test or Fisher exact test where appropriate. A p-value <0.05 will be considered statistically significant.