Natl. J. Physiol. Pharm. Pharmacol. (2025), Vol. 15(1): 114–118

Research Article

10.5455/NJPPP.2025.v15.i1.20

Effectiveness and safety of carboxymethyl cellulose eye drops in dry eye disease: A real-world study

Aditi Agashe, Janarthanan R., Ajitkumar Gondane*, Dattatray Pawar, Akhilesh Sharma

Medical Affairs Division, Alkem Laboratories, Mumbai, India

*Corresponding Author: Ajitkumar Gondane. Medical Affairs Division, Alkem Laboratories, Mumbai, India. Email: ajitkumar.gondane [at] alkem.com

Submitted: 08/11/2024 Accepted: 16/12/2024 Published: 31/01/2025

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ABSTRACT

Background: Dry eye disease (DED) is a prevalent multifactorial disorder that affects individuals worldwide and is characterized by insufficient tear production or excessive tear evaporation. Carboxymethyl cellulose (CMC) eye drops are widely used for managing DED because of their bio-adhesive properties, which enhance tear retention. However, real-world data on its effectiveness and safety are lacking.

Aim: To evaluate clinical effectiveness and safety in diverse real-world clinical settings.

Methods: This multicenter, retrospective, real-world study assessed the medical records of adult patients with DED treated with CMC eye drops. The severity of symptoms, such as pain, dryness, irritation, poor vision, and sensitivity to light, was assessed using a Likert scale at baseline and follow-up visits. Tear break-up time (TBUT) and adverse events were recorded during follow-up. Data were analyzed using descriptive statistics.

Results: A total of 1853 patients (mean age [±SD]), 43.78 ± 10.66 years; males, 63%) were included in the analysis. The duration of illness noted varied from 0.5 to 100 weeks. CMC 0.5% or 1% eye drops were prescribed at a frequency of twice, three times, or four times daily depending on the disease severity. The majority of patients were followed up after 1 month, with an average follow-up duration of 47.30 days. From baseline to follow-up assessment visit, the severity of pain, dryness, irritation, poor vision, and sensitivity to light were reduced by 80%, 68%, 77%, 72%, and 78%, respectively. TBUT was documented at the follow-up visit in 772 patients; of these, 99% of patients had a normal TBUT (≥10 seconds) and no patient had an abnormal TBUT (<5 seconds). No adverse events were reported during the study period.

Conclusion: CMC eye drops significantly reduced DED symptoms and showed a favorable safety profile, with no adverse events and normal tear break-up times in most patients.

Keywords: Tear break-up time (TBUT), Retrospective study, CMC, DED.

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Introduction

Dry eye disease (DED) is a global condition that is traditionally associated with the older population but is now increasingly affecting younger individuals, primarily due to increased screen time (Talens-Estarelles et al., 2021; Al-Mohtaseb et al., 2021). The global prevalence rate of DED has been identified to be 5%–50%, depending on the geographical disorder (Honavar 2023). The prevalence increases with age, and a higher incidence is observed in women than in men. In fact, the female sex is a significant risk factor for the development of dry eye, especially in postmenopausal women (Garcia-Alfaro et al., 2021). DED is a multifactorial disorder of the ocular surface characterized by insufficient tear production or excessive tear evaporation, leading to discomfort, visual disturbances, and damage to the ocular surface (Golden et al., 2024). Certain risk factors that may contribute to the development of DED include age, sex, lifestyle, sociodemographic factors, environmental factors, concomitant diseases (glaucoma, diabetes mellitus, human immunodeficiency virus, and so on), and medications (anti-anxiety, beta blockers, calcium channel blockers, loop diuretics, and cholesterol-lowering agents) (Hasan 2021). DED can be identified by various symptoms, including redness, burning, stinging, foreign body sensation, pruritus, and photophobia (Lemp and Foulks 2007).

The management of DED follows a stepwise approach that aligns with the severity of the condition and considers factors such as associated meibomian gland dysfunction, potential inflammation of the ocular surface, and any related systemic diseases (Pflugfelder et al., 2007). The treatment options currently available for DED include artificial tears, anti-inflammatory agents (Anakinra), topical corticosteroids, topical cyclosporine A 0.05% eyedrop, tacrolimus 0.03% eyedrop, tetracyclines (40–400 mg/day doxycycline), macrolides (azithromycin 1%), omega-3 fatty acids, and so on (Messmer 2015). Artificial tears serve as the primary remedy for DED comprising various formulations, including carboxymethyl cellulose (CMC) and hyaluronic acid (HA). CMC has favorable bio-adhesive properties, which leads to an enhancement in tear retention time. On the other hand, HA formulations possess the capability to bind water molecules and prevent dehydration (Peppas and Buri 1985; Song et al., 2017). Numerous large-scale clinical studies have demonstrated the efficacy of both CMC and HA in alleviating signs and symptoms of DED. To determine the superior treatment, several studies have compared the effectiveness of CMC and HA using various assessment methods, such as tear break-up time (TBUT), corneal or conjunctival staining, Schirmer’s test, and dry eye symptom scoring, in which both drugs displayed similar efficacy (Lee et al., 2011; Brignole et al., 2005).

While some studies have found comparable effectiveness between CMC and HA, indicating no significant difference in their therapeutic outcomes, others have observed superior efficacy between the two treatments. However, despite their widespread use, there remains an urgent need to comprehensively evaluate the real-world effectiveness and safety profile of CMC eye drops in patients undergoing DED. This retrospective study sought to address this gap by assessing the effectiveness and safety of CMC eye drops in patients diagnosed with DED in a real-world scenario.

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Methods

This is a multicenter, retrospective, medical records-based, real-world evidence, and single-arm study. The study was initiated after receiving ethics committee approval. The data were collected from approximately 500 centers. The medical records of 1853 patients were collected from June to September 2024. Patients in all age groups diagnosed with DED who received 0.5% or 1% CMC eye drops were included in the analysis. Patients with incomplete medical records were excluded from the study. The patient records were captured using an Excel sheet. Each patient’s records were assigned a unique ID number, starting with 001, for each investigator. The index date on which CMC treatment was initiated was considered the baseline visit. Data were collected from the start of treatment until the posttreatment follow-up, which was approximately 1–3 months after therapy. At the start of therapy, demographic details (age in years and gender), medical history [clinical characteristics, including duration and severity of DED, severity of clinical symptoms, and concomitant ocular medications for current medical illness (if any)], and treatment dose, frequency, and duration of CMC prescribed were collected. At the post-treatment follow-up between 1 and 3 months, data on the duration of therapy, severity of clinical symptoms, TBUT (if available), and adverse events reported during treatment were also captured. Microsoft Excel was used for data analysis. The data collected from the database were analyzed for demographic characteristics, effectiveness, and safety. Data were presented as mean ± SD or number (percentage). Descriptive statistics were used. A p-value of <0.05 was considered statistically significant.

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Results

A total of 1853 patients from approximately 500 centers who received 0.5% or 1% CMC eyedrops from June to September 2024 were included in the analysis. Among the total participants, 1,169 were male and 684 were female. The duration of illness noted varied from 0.5 to 100 weeks, with an average duration of 5.89 weeks. Patients were prescribed 0.5% or 1% CMC eye drops, depending on disease severity, at a frequency of twice, thrice, or four times daily. The majority of patients were followed up after 1 month, with an average follow-up duration of 47.30 days. The reduction in symptom severity was calculated according to the decrease in symptom scores from baseline to follow-up visits.

Patient demographics

Table 1 shows the gender distribution of the analyzed patients. Out of 1853 patients analyzed, 1169 were male and 684 were female. Table 2 shows the average age of the patients analyzed. The age of patients ranged from 7 to 80 years. The mean age of patients noted was 43.78 years. The male patient had a mean age of 44.56 years and the female patient had a mean age of 44.56 and 42.42 years.

Duration of illness

Table 3 illustrates the distribution of patients with DED according to the duration of their condition. This result highlights that a significant proportion of patients (34.97%) have experienced symptoms for less than 4 weeks, whereas the percentage decreases notably in subsequent categories. The number of patients with DED decreased progressively for 4 weeks (27.52%) to those with symptoms lasting beyond 12 weeks (1.45%).

Decrease in the severity of ocular symptoms from baseline to follow-up visit (Assessment 1 vs. Assessment 2)

The severity of ocular symptoms, such as pain, dryness, irritation, poor vision, and sensitivity to light, was captured at baseline and follow-up visits. Each symptom was given a score from 0 to 3 (0 being no symptom and 3 being severe symptom). The mean score for each symptom was compared from baseline visit (assessment 1) and follow-up visits (assessment 2) as shown in fig 1. Table 4 presents the percentage reduction in each symptom from the baseline visit to follow-up visit. The findings demonstrate a notable decrease in the severity of all symptoms. From baseline to follow-up assessment visit, it was noted that the severity of pain, dryness, irritation, poor vision, and sensitivity to light were reduced by 80%, 68%, 77%, 72%, and 78%, respectively.

Fig. 1. Reduction in symptom severity from assessment 1 to assessment 2.

Table 1. Gender distribution of participants.

Table 2. Mean age of participants by gender.

Table 3. Duration of illness.

Tear break-up time

The tear break-up time test data were available for 772 evaluated patients with DED at follow-up visits. Table 5 presents the number of patients with normal (10–35 seconds), marginal (5–10 seconds), and abnormal (less than 5 seconds) TBUT. A majority of participants (762) exhibited a normal TBUT, with only 10 participants classified as marginal, and none of the patients had an abnormal TBUT (<5 seconds). These results indicate that CMC plays an important role in the stability of tear films.

The mean age of patients with DED was 43.78 years, and most experienced symptoms for less than 4 weeks, indicating its presentation in the young population as well. The study demonstrated that CMC eye drops effectively managed DED in most of the patients, showing marked symptom improvement—reductions of 68%–80% in pain, dryness, irritation, poor vision, and light sensitivity. Additionally, tear break-up time (TBUT) results indicated improved tear film stability, with most patients achieving normal TBUT values. These findings suggest that CMC eye drops not only relieve DED symptoms but also enhance ocular surface health, supporting their beneficial role in managing DED.

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Discussion

This study aimed to gain a profound understanding of the application of CMC in the context of DED. The main goal of this study was to assess the clinical effectiveness and safety profile of CMC eye drops for the treatment of DED in real-world clinical practice.

CMC is an anionic polymer of glucopyranose subunits that helps in water retention and has moistening properties; thus, it is often employed as a thickener, stabilizer, and film-forming agent (Salim et al., 2023; Rahman et al., 2021). CMC is a widely utilized cellulose derivative, and it has versatile applications across various industries, including pharmaceuticals, food, and biotechnology (Liu et al., 2021). In ophthalmology, CMC-based artificial tears are commonly used to treat DED by improving ocular surface hydration and enhancing tear film stability (Garrett et al., 2007). Its efficacy in alleviating dry eye symptoms is dose-dependent, with higher concentrations, such as 1.0%, showing superior effectiveness compared to lower concentrations such as 0.5% (Garrett et al., 2007). Additionally, CMC’s prolonged retention time on the ocular surface allows for better lubrication and cytoprotection, promoting epithelial wound healing after LASIK surgery, and minimizing dry eye symptoms (Garrett et al., 2007). Furthermore, CMC is highly biocompatible and reduces ocular irritation in contact lens wearers by minimizing corneal staining and enhancing lens comfort (Garrett et al., 2007).

Table 4. Percentage reduction in symptom severity from assessment 1 to assessment 2.

Table 5. Tear break-up time.

Numerous large-scale clinical studies have demonstrated the efficacy of both CMC and HA in alleviating the signs and symptoms of DED. To determine the superior treatment, several studies have compared the effectiveness of CMC and HA using various assessment methods, such as TBUT, corneal or conjunctival staining, Schirmer’s test, and dry eye symptom scoring, in which both drugs displayed equal potency (Lee et al., 2011; Brignole et al., 2005).

While some studies have found comparable effectiveness between CMC and HA, indicating no significant difference in their therapeutic outcomes, others have observed superior efficacy between the two treatments.

This multicenter, retrospective study assessed the efficacy and safety of CMC eye dropsy in 1853 patients with DED, primarily men (63.1%) with an average age of 44 years.

Most patients had experienced symptoms for 4–12 weeks before treatment. After 3–6 months of CMC use, significant improvements were observed, with reductions in discomfort (79.61%), dryness (67.77%), irritation (77.12%), impaired vision (71.69%), and light sensitivity (78.26%). Similarly, a study conducted by Garrett et al. (2007) investigated the effects of CMC on corneal epithelial wound healing and its potential role in alleviating the symptoms of dry eye disease. This research included both in vitro and in vivo experiments in which CMC was applied to human corneal epithelial cells and rabbit models with induced corneal scrape wounds. The findings revealed that CMC is effective in treating aqueous tear-deficient dry eye symptoms and ocular surface staining. The effect of CMC was found to be dose-dependent, with greater improvement observed with higher concentrations (1.0% CMC compared to 0.5% CMC) (Garrett et al., 2007).

Additionally, the TBUT improved in 98.7% of patients, reflecting enhanced tear film stability due to CMC’s bio-adhesive properties. A similar study by Song et al. (2017) performed a systematic review and meta-analysis to reconcile the differing results by pooling data from relevant studies and conducting a thorough analysis to determine the most efficacious treatment option between CMC and HA, which revealed no significant differences between the CMC and HA groups for TBUT. However, significant improvements in the CMC group compared with the HA group in terms of change in tear break-up time from baseline were observed (Song et al., 2017).

Yao et al. (2015) performed a multicenter, open-label, randomized controlled trial (RCT) in which they evaluated the efficacy and safety of CMC 1% ophthalmic solution combined with conventional therapy in treating DED in which they noticed a substantial rise in TBUT among patients in the treatment cohort when compared with the control group. Additionally, there were no noteworthy variances detected in terms of tolerability and safety between the group undergoing CMC treatment alongside conventional therapy and those solely receiving conventional therapy (Yao et al., 2015).

This study evaluating the effectiveness and safety of CMC eye drops in more than 1,800 patients with DED identified valuable strengths and limitations. The large, diverse sample size and insights from multiple centers provide robust, generalizable findings that reflect actual clinical practice, enhancing its relevance. However, the retrospective design introduces limitations such as the absence of randomization, potential selection bias, reliance on variable data quality, and lack of a control group, which can impact the conclusions. Despite these limitations, this study provides significant real-world evidence on the therapeutic use of CMC eye drops in DED.

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Conclusion

This retrospective multicenter study provides robust real-world evidence supporting the effectiveness and safety of CMC eye drops in managing DED. CMC eye drops have emerged as a viable first-line treatment option, largely due to their excellent safety profile, characterized by minimal and nonsevere side effects. These findings underscore the importance of early intervention and consistent treatment adherence for optimizing DED management. Clinicians can leverage this evidence to enhance patient outcomes by highlighting the therapeutic benefits of CMC eye drops in alleviating symptoms and improving the quality of life for individuals suffering from DED.

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