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ORIGINAL ARTICLE
Year : 2017  |  Volume : 24  |  Issue : 4  |  Page : 202-206  

Comparison of the efficacy of carboxymethylcellulose 0.5%, hydroxypropyl-guar containing polyethylene glycol 400/propylene glycol, and hydroxypropyl methyl cellulose 0.3% tear substitutes in improving ocular surface disease index in cases of dry eye


1 Department of Ophthalmology, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India
2 Department of Community Medicine, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India

Date of Web Publication12-Jan-2018

Correspondence Address:
Prafulla K Maharana
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, Room-S5, 1st Floor, All India Institute of Medical Sciences, New Delhi-110029
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/meajo.MEAJO_165_15

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   Abstract 

PURPOSE: To compare the efficacy of carboxymethylcellulose 0.5% (CMC), hydroxypropyl-guar containing polyethylene glycol 400/propylene glycol (PEG/PG), and hydroxypropyl methylcellulose 0.3% (HPMC) as tear substitutes in patients with dry eye.
METHODS: A retrospective evaluation of cases presenting with symptoms of dry eye from July 2014 to June 2015 was done. Patients with Ocular Surface Disease Index (OSDI) scoring >12 were included in the study. Parameters such as age, gender, Schirmer test (ST), and tear film breakup time (TBUT) were recorded on day 0, week 1, and week 4. For analysis, cases were divided into three groups; Group 1 – CMC, Group 2 – PEG/PG, and Group 3 – HPMC.
RESULTS: Overall, 120 patients were included in the study. Demographic data and baseline characteristics were comparable among the groups. Group 2 had significant improvement in percentage change in OSDI (weeks 0–1, 0–4, and 1–4, P = 0.00), TBUT (weeks 0–1, P = 0.01; 0–4, P = 0.006; and 1–4, P = 0.007), and in ST (weeks 0–1, P = 0.02; 0–4, P = 0.002; and 1–4, P = 0.008) compared to Group 1 at all follow-ups. Group 3 had improvements similar to Group 2, but it was not at all follow-ups (improvement in percentage change OSDI [weeks 0–1, 0–4, and 1–4, P = 0.00], TBUT [weeks 0–1, P = 0.10; 0–4, P = 0.03; and 1–4, P = 0.04], and in ST [weeks 0–1, P = 0.007; 0–4, P = 0.03; and 1–4, P = 0.12]). No significant difference was found between Groups 2 and 3.
CONCLUSIONS: Hydroxypropyl-guar containing PEG/PG and HPMC as tear substitutes are better than CMC. While HPMC was comparable to PEG/PG in subjective improvement, the objective improvement was not consistent.

Keywords: Artificial tear, carboxymethylcellulose, dry eye, hydroxypropyl methylcellulose, Ocular Surface Disease Index, polyethylene glycol


How to cite this article:
Maharana PK, Raghuwanshi S, Chauhan AK, Rai VG, Pattebahadur R. Comparison of the efficacy of carboxymethylcellulose 0.5%, hydroxypropyl-guar containing polyethylene glycol 400/propylene glycol, and hydroxypropyl methyl cellulose 0.3% tear substitutes in improving ocular surface disease index in cases of dry eye. Middle East Afr J Ophthalmol 2017;24:202-6

How to cite this URL:
Maharana PK, Raghuwanshi S, Chauhan AK, Rai VG, Pattebahadur R. Comparison of the efficacy of carboxymethylcellulose 0.5%, hydroxypropyl-guar containing polyethylene glycol 400/propylene glycol, and hydroxypropyl methyl cellulose 0.3% tear substitutes in improving ocular surface disease index in cases of dry eye. Middle East Afr J Ophthalmol [serial online] 2017 [cited 2021 Oct 23];24:202-6. Available from: http://www.meajo.org/text.asp?2017/24/4/202/223104




   Introduction Top


Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability, with potential damage to the ocular surface.[1] It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface.[1] Dry eye is one of the most common causes of ocular morbidity in patients presenting to an ophthalmology outpatient department. Approximately one out of seven individuals aged 65–84 years reports symptoms of dry eye often or all of the time.[2] Management of dry eye depends on the cause and severity of the condition.[1] Various strategies have been described for medical management of dry eye; these include, the topical use of lubricants (artificial tear substitutes), topical corticosteroids and anti-inflammatory therapies, cyclosporine ophthalmic emulsion, and the systemic use of antioxidants (e.g., omega-3 fatty acids).[1],[2]

Artificial tears are aqueous solutions containing polymers that determine their viscosity, retention time, and adhesion to the ocular surface. Various polymers currently in use include cellulose derivatives (e.g., hydroxypropyl methylcellulose [HPMC], carboxymethylcellulose [CMC]), polyvinyl derivatives (e.g., polyvinyl alcohol), chondroitin sulfate, and sodium hyaluronate.[1],[3] In mild-to-moderate cases, they are the mainstay of treatment. Artificial tears act by replenishing the deficient aqueous layer of the tear film and diluting the inflammatory cytokines.[1],[2],[3]

In this study, we compared the efficacy of three commonly used tear substitutes, i.e., CMC 0.5%, HPMC 0.3%, and hydroxypropyl-guar containing polyethylene glycol 400/propylene glycol (PEG/PG) in the treatment of patients with dry eye.


   Methods Top


Medical records of all cases of clinically diagnosed dry eye attending the corneal clinic of Department of Ophthalmology, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India, from July 2014 to June 2015, were reviewed. The protocol for this study was approved by the local Institutional Review Board/Ethical Committee. The study adhered to the tenets of the Declaration of Helsinki. Inclusion criteria for the study were cases with Ocular Surface Disease Index (OSDI) scoring[4] of >12 and cases in whom topical steroid in the form of loteprednol 0.5% and cyclosporine 0.05% was started along with topical lubricants. We excluded cases in whom only topical lubricants or either steroid or cyclosporine was prescribed, cases already on treatment for dry eye, cases in whom dry eye was secondary to some ocular or systemic disease, and patients with any concurrent disease or condition that could have complicated or interfered with the administration or evaluation of the study drug.

The OSDI is a validated questionnaire-based scoring system for diagnosis of dry eye.[5] It consists of 12 questions that provide a rapid assessment of the symptoms of ocular irritation and their impact on vision-related functions. The response to each item was scored from 0 (none of the time) to 4 (all of the time); an average score was generated and transformed into a scale of 0–100, with higher scores representing greater disability.[4],[5],[6]

For the purpose of analysis, the cases were categorized into three groups; Group-1 included cases prescribed CMC 0.5% four times a day (prepared at our compound pharmacy), Group-2 included cases prescribed with hydroxypropyl-guar containing PEG/PG (Systane Ultra, Novartis [India] Ltd.) twice a day, and Group-3 included cases prescribed with HPMC 0.3% (Genteal Eye Drops, Novartis [India] Ltd.). Details of demographic data such as age and sex were recorded. Parameters such as OSDI, tear film breakup time (TBUT), Schirmer test (ST), and slit-lamp examination findings were recorded at day 0 (before start of treatment), week 1, and week 4. Comparative analysis was done among different groups for improvement in OSDI scores, TBUT, and ST at each follow-up.

Statistical methods

The efficacy variables included TBUT, ST, and OSDI score. All variables were evaluated at days 0, 1 week, and 4 weeks. A repeated measures analysis of variance (ANOVA) was used to test for mean treatment group differences by day changes from baseline of TBUT, ST, and individual OSDI scores. ANOVA test was used to compare mean differences between treatment groups at day 0, week 1, week 4 in the OSDI score, TBUT, ST, and age characteristics. To find out which of the three drugs were most effective, post hoc test (Games–Howell) is applied which compares the drugs one by one. The Chi-square test was used to compare treatment group differences in demographic characteristics.


   Results Top


One hundred and twenty patients were included in the study. Group 1 (CMC 0.5%), Group 2 (hydroxypropyl-guar containing PEG/PG), and Group 3 (HPMC 0.3%) included 41, 48, and 31 cases, respectively. Male patients accounted for 53.3% of the cases. The mean age in Group 1, Group 2, and Group 3 was 44.10 ± 17.82, 49.21 ± 15.31, and 42.58 ± 16.21 years, respectively. Demographic data were similar across treatment groups as shown in [Table 1]. The three groups were comparable in their baseline characteristics that included mean scores for OSDI (P = 0.462), mean TBUT (P = 0.172), and the mean scores for ST (P = 0.226) [Table 1]. Cases were divided into mild, moderate, and severe depending on the OSDI score (mild: 13–22 points, moderate: 23–32 points, and severe: 33–100 points).[7] There was no difference in severity between the three groups (P = 0.827) [Table 1].
Table 1: Comparison of patients' baseline characteristics between Groups 1, 2, and 3*

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Ocular Surface Disease Index

Mean OSDI in Group 1 was 30.14 ± 11.57 at week 1 and 25.78 ± 11.86 at week 4. Mean OSDI in Group 2 was 24.88 ± 9.66 at week 1 and 14.28 ± 6.83 at week 4. Mean OSDI in Group 3 was 28.86 ± 15.83 at week 1 and 17.98 ± 11.89 at week 4. Patients in Group 2 had a significantly lower mean OSDI score than those in Group 1 at week 1 (P = 0.000) and at week 4 (P = 0.000). Patients in Group 3 had a significantly lower mean OSDI score than those in Group 1 at week 1 (P = 0.001) and at week 4 (P = 0.000). Patients in Group 2 and Group 3 had no significant difference in mean OSDI score at week 1 (P = 0.541) and week 4 (P = 0.717). Change in OSDI at 1 week in Group 1 was 16.32%, in Group 2, it was 35.13%, and in Group 3, it was 31.5%. Change in OSDI at week 4 in Group 1 was 29.17%, in Group 2, it was 62.9%, and in Group 3, it was 57.3%.

Patients in Group 2 had a significantly better percentage change in OSDI than those in Group 1; at 0–1 week (P = 0.000), 0–4 weeks (P = 0.000), and 1–4 weeks (P = 0.000) [Table 2]. Patients in Group 3 had a significantly better percentage change in OSDI than those in Group 1, at 0–1 week (P = 0.000), 0–4 weeks (P = 0.000), and 1–4 weeks (P = 0.000). Patients in Group 2 and Group 3 had no significant difference in percentage change in OSDI at 0–1 week (P = 0.138), 0–4 weeks (P = 0.45), and 1–4 weeks (P = 0.113).
Table 2: Comparison of percentage change in Ocular Protection Disease Index score between Groups 1, 2, and 3

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Tear breakup time

Mean TBUT in Group 1 was 9.20 ± 2.15 at week 1 and 9.57 ± 1.88 at week 4. Mean TBUT in Group 2 was 8.88 ± 2.33 at week 1 and 9.96 ± 1.64 at week 4. Mean TBUT in Group 3 was 8.88 ± 2.43 at week 1 and 9.85 ± 1.64 at week 4. Patients in Group 2 had a significant increase in mean TBUT than those in Group 1 at week 1 (P = 0.003) and at week 4 (P = 0.001). Patients in Group 3 had no significant difference in improvement in TBUT than those in Group 1 at week 1 (P = 0.06), but there was significant improvement of TBUT at week 4 (P = 0.014). There was no significant difference in improvement of TBUT in Group 2 and Group 3 at week 1 (P = 0.984) and at week 4 (P = 0.936).

Percentage change in TBUT among the three groups is summarized in [Table 3]. Patients in Group 2 had a significantly better percentage change in TBUT than those in Group 1; at 0–1 week (P = 0.016), 0–4 weeks (P = 0.006), and 1–4 weeks (P = 0.007). Patients in Group 3 had no significant difference in percentage change in TBUT than those in Group 1 at 0–1 weeks (P = 0.105), but there was a significant difference at 0–4 weeks (P = 0.032) and 1–4 weeks (P = 0.046). Patients in Group 2 and Group 3 had no significant difference in percentage change in TBUT from 0 to 1 week (P = 0.996), 0 to 4 weeks (P = 0.984), and 1 to 4 weeks (P = 0.982).
Table 3: Comparison of percentage change in tear film breakup time between Groups 1, 2, and 3

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Shirmer's test

Mean ST in Group 1 was 25.78 ± 8.03 at week 1 and 26.06 ± 7.57 at week 4. Mean ST in Group 2 was 24.25 ± 8.37 at week 1 and 26.33 ± 6.67 at week 4. Mean ST in Group 3 was 23.72 ± 9.93 at week 1 and 25.46 ± 8.52 at week 4. Patients in Group 2 exhibited significant improvement in ST than Group 1 at week 1 (P = 0.018) and week 4 (P = 0.000). Patients in Group 3 exhibited significant improvement in ST than those in Group 1 at week 1 (P = 0.028) and week 4 (P = 0.015). There was no significant difference in improvement of ST in Group 2 and Group 3 at week 1 (P = 0.994) and week 4 (P = 0.939).

The percentage change in ST in the three groups is summarized in [Table 4]. Patients in Group 2 had a significant difference in percentage change in ST than Group 1 at 0–1 week (P = 0.029), 0–4 weeks (P = 0.002), and 1–4 weeks (P = 0.008). Patients in Group 3 had a significant difference in percentage change in ST than those in Group 1 at 0–1 week (P = 0.033) and 0–4 weeks (P = 0.033), but no significant difference at 1–4 weeks (P = 0.120). Patients in Group 2 and Group 3 had no significant difference in percentage change in ST at 0–1 week (P = 0.997), 0–4 weeks (P = 0.863), and 1–4 weeks (P = 0.904).
Table 4: Comparison of percentage change in Schirmer's test between Groups 1, 2, and 3*

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   Discussion Top


Tear substitutes are an essential component of the treatment regimen of dry eye. The OSDI has been used previously for the diagnosis of dry eye.[5] The OSDI scoring is probably a more practical approach to evaluate the improvement in dry eye from a patient's perspective. In this study, both hydroxypropyl-guar containing PEG 400/PG and HPMC 0.3% were better compared to CMC 0.5% in improving the OSDI.

The improvement with hydroxypropyl-guar containing PEG/PG as a tear substitute was consistent at all follow-ups compared to CMC 0.5%. In addition to OSDI, improvement was also seen in other objective parameters analyzed, that is, ST and TBUT. Hydroxypropyl-guar containing PEG/PG works through a unique biphasic mechanism of action in which the product first binds to damaged hydrophobic areas of epithelial cells to add volume to the tear film, and then restructures the tear film by forming a protective gel matrix that provides long-lasting protection.[8] The high molecular weight (1000–5000 kDa) hydroxypropyl-guar molecules, along with the natural mucin layer, prolong retention of the demulcents on the ocular surface, which provides sustained lubrication of the eye. This protects the ocular surface from further damage during the process of epithelial healing and remodeling.[8] In addition, the new formulation has sorbitol, which serves to optimize the viscosity of the drop through control of the aforementioned borate/hydroxypropyl-guar gel.[8],[9] In clinical studies, the daily use of PEG/PG, for 28 days or more in patients with dry eye, has been consistently associated with significant decrease in conjunctival and/or corneal staining,[10],[11],[12],[13],[14] increase in TBUT (invasive or noninvasive),[13],[15] in patient-assessed parameters (drop comfort, ocular comfort, and dry eye symptoms), and a significantly greater ocular protection index.[15] The result of our study corroborates with those of previous studies. Thus, it can be concluded that hydroxypropyl-guar containing PEG/PG can lead to early and sustained relief in both objective and subjective parameters compared to CMC 0.5% tear substitutes.

The percentage change in OSDI in Group 3 cases on HPMC, when compared to those in Group 1, showed a trend similar to patients in Group 2, with significantly better change at all follow-up. This can be attributed to hydroxypropyl methylcellulose's superior cohesive and emollient properties compared to CMC.[16] However, unlike Group 2, the improvement in objective parameters such as TBUT was not consistent throughout the entire follow-up period. It was significant at week 1–4 and 0–4 but not in the 1st week (0–1 week) of starting therapy. The percentage change in ST was also inconsistent unlike Group 2. It was significant at 0–1 week (P = 0.007) and 0–4 weeks (P = 0.033) but not significant at 1–4 weeks' follow-up (P = 0.120). When Groups 2 and 3 were compared, no significant difference was found in any of the parameters at any follow-up. Thus, it can be said, although HPMC can provide immediate symptomatic relief to patients with dry eye similar to hydroxypropyl-guar containing PEG/PG, in terms of objective improvement such as TBUT and ST, it is not as consistent as hydroxypropyl-guar containing PEG/PG.

The limitation of using OSDI scoring is that it can be biased by possible mistakes owing to misunderstanding of words, reflecting individual and regional differences in word choice, rather than different quality of responses.[5],[6] Moreover, the level of tolerance can also vary among different patients. All these factors can lead to variable scores even in patients with equal severity of dryness. Also, a study by Fenga et al.[6] found that OSDI is not as reliable as tear osmolarity for diagnosis of dry eye. To avoid such bias, we included both TBUT and ST, which showed results similar to OSDI scoring.


   Conclusion Top


To conclude, both artificial tears such as hydroxypropyl-guar containing PEG 400/PG and HPMC 0.3% are equally effective in improving the subjective component of dry eye while the improvement in objective parameters is more consistent with hydroxypropyl-guar containing PEG 400/PG tear substitutes.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
The epidemiology of dry eye disease: Report of the Epidemiology Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007;5:93-107.  Back to cited text no. 1
    
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Unlü C, Güney E, Akçay Bİ, Akçalı G, Erdoǧan G, Bayramlar H, et al. Comparison of ocular-surface disease index questionnaire, tear film break-up time, and Schirmer tests for the evaluation of the tear film in computer users with and without dry-eye symptomatology. Clin Ophthalmol 2012;6:1303-6.  Back to cited text no. 5
    
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Christensen MT, Cohen S, Rinehart J, Akers F, Pemberton B, Bloomenstein M, et al. Clinical evaluation of an HP-guar gellable lubricant eye drop for the relief of dryness of the eye. Curr Eye Res 2004;28:55-62.  Back to cited text no. 8
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Rolando M, Autori S, Badino F, Barabino S. Protecting the ocular surface and improving the quality of life of dry eye patients: A study of the efficacy of an HP-guar containing ocular lubricant in a population of dry eye patients. J Ocul Pharmacol Ther 2009;25:271-8.  Back to cited text no. 12
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Versura P, Profazio V, Campos EC. One month use of systane improves ocular surface parameters in subjects with moderate symptoms of ocular dryness. Clin Ophthalmol 2008;2:629-35.  Back to cited text no. 13
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Davitt WF, Bloomenstein M, Christensen M, Martin AE. Efficacy in patients with dry eye after treatment with a new lubricant eye drop formulation. J Ocul Pharmacol Ther 2010;26:347-53.  Back to cited text no. 14
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Ousler GW, Michaelson C, Christensen MT. An evaluation of tear film breakup time extension and ocular protection index scores among three marketed lubricant eye drops. Cornea 2007;26:949-52.  Back to cited text no. 15
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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