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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 3  |  Issue : 1  |  Page : 9-13

Comparative observational analysis of clinical outcomes in patients of vernal keratoconjunctivitis treated with eye drops olopatadine or bepotastine besilate


1 Department of Ophthalmology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
2 Department of Pharmacology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India

Date of Submission23-Jun-2020
Date of Decision10-Sep-2020
Date of Acceptance16-Oct-2021
Date of Web Publication28-Apr-2022

Correspondence Address:
Dr. Ajai Agrawal
Department of Ophthalmology, All India Institute of Medical Sciences, Rishikesh - 249 203, Uttarakhand
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JME.JME_107_20

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  Abstract 


Objective: Observation and comparison of resolution of signs and relief of symptoms in patients of Vernal Keratoconjunctivitis (VKC) treated with 0.1% olopatadine eye drops or 1.5% bepotastine besilate eye drops. Materials and Methods: It was a prospective observational study of 60 patients of VKC from January 2018 to July 2019. Thirty confirmed cases of VKC were included in the study in each group. One group received 0.1% olopatadine eye drops and second group received 1.5% bepotastine besilate eye drops and were followed up for a period of 4 weeks. The main outcome measures were scoring and comparison of Total subjective symptom scores (TSSS) and Total objective sign scores (TOSS) within and between the groups at each follow up. Wilcoxon rank-sum test (Mann Whitney U test) was used to compare the two groups in terms of symptom and sign score at each of the time points. Friedman test was used to explore the change in score over time within each group. Generalized Estimating Equations method was used to explore the difference in change in score between the two groups over time. A p value of < 0.05 was considered statistically significant. Results: With treatment both TSSS and TOSS decreased consistently in both groups at the end of the two week and four week follow up time points. P Value of Comparison of the Two Groups in Terms of Difference of Subjective Score Total from Baseline to Follow-up Time points was statistically significant (P<0.001). Conclusion: At the end of the study, olopatadine 0.1 % eye drops was found to be more efficacious than 1.5% bepotastine besilate eye drops both for relief of symptoms and resolution of signs.

Keywords: Vernal keratoconjunctivitis, Olopatadine 0.1%, Bepotastine besilate 1.5%


How to cite this article:
Yadav P, Agrawal A, Dhamija P, Singh A, Mittal SK, Samanta R. Comparative observational analysis of clinical outcomes in patients of vernal keratoconjunctivitis treated with eye drops olopatadine or bepotastine besilate. J Med Evid 2022;3:9-13

How to cite this URL:
Yadav P, Agrawal A, Dhamija P, Singh A, Mittal SK, Samanta R. Comparative observational analysis of clinical outcomes in patients of vernal keratoconjunctivitis treated with eye drops olopatadine or bepotastine besilate. J Med Evid [serial online] 2022 [cited 2022 Oct 6];3:9-13. Available from: http://www.journaljme.org/text.asp?2022/3/1/9/344279




  Introduction Top


Vernal keratoconjunctivitis (VKC) is a recurrent chronic inflammatory disease of the conjunctiva. The disease primarily affects children and adolescents. In patients under 20 years of age, the male:female ratio is 3–4:1,[1],[2] whereas the ratio in those older than 20 years of age is 1:1 with onset, generally from about the age of 5 years onwards.[1],[2],[3] Greater prevalence is seen in the regions with hot, humid climate and higher load of airborne allergens. The signs and symptoms of VKC usually occur from April to August, although some patients have a perennial form of the disease.[4] The reported risk of visual loss is generally greater in tropical countries, which is about 10%.[5],[6] The state of Uttarakhand located in the foothills of the Himalayas has climate predisposing to VKC.[7]

The disease may present in three clinical forms: palpebral, limbal and mixed form. The patients generally present with itching, watering, hyperaemia, photophobia and sticky discharge. On ocular examination, conjunctival hyperaemia, chemosis, sticky and/or filamentous mucus discharge, papillary hypertrophy on the upper tarsal conjunctiva and localised swelling and edema of limbal conjunctiva (Trantas dots) can be found, along with punctate epitheliopathy, epithelial erosions, ulcers and plaques when the cornea is involved.

Therapy of VKC includes the use of topical vasoconstrictors, antihistamines, inhibitors of mast cell degranulation, corticosteroids and immunomodulators. The continuous search for safer and effective treatment for VKC is an ever-developing arena. The latest topical anti-allergy medications for allergic conjunctivitis are the dual-action agents, which combines strong antihistaminic activity with mast cell-stabilising properties to provide both rapid and long-lasting relief. These multimodal agents combine the actions of histamine receptor antagonists, superior to previous generation antihistamines, coupled with the actions of mast-cell stabilisers. These collective mechanisms provide immediate and sustained relief during both early and late-phase ocular allergic reactions.[8],[9] Some of the dual-acting antihistamines are olopatadine, ketotifen, epinastine, azelastine, bepotastine and alcaftadine. With an array of dual-acting agents presently available, we assessed the resolution of clinical symptoms and signs with 0.1% olopatadine hydrochloride versus 1.5% bepotastine besilate ophthalmic solution. There have been quite a few studies evaluating the efficacy and/or side effect profile of 0.1% olopatadine eye drops and 1.5% bepotastine besilate ophthalmic solution individually as well as their comparisons with other drugs separately. However, there is a paucity of literature comparing the efficacy and the side effect profile of the above two drugs. In this study, we observed and recorded the resolution of symptoms and signs, eye drop comfort and preferred medicine when treating VKC with eye drop bepotastine besilate 1.5% compared with eye drop olopatadine hydrochloride 0.1% over a 4-week period.


  Materials and Methods Top


This study adhered to the Declaration of Helsinki and institute ethical clearance was obtained prior to conducting the study. It was a prospective observational study conducted in the Department of Ophthalmology at a tertiary care centre of North India over a period of 1½ years from 1 January 2018- to 31 July 2019. The study is registered under the Clinical Trials Registry of India (CTRI No): CTRI/2018/03/012788.

Patients with a clinical diagnosis of VKC, of either gender, >5 years of age and who gave written consent for all required study visits and were ready to follow instructions from study investigators were included in the study. Patients in active stage of any other ocular inflammatory disease besides VKC, other causes of allergic conjunctivitis, presence of glaucoma, uveitis, patients on any oral or topical steroids, pregnant or lactating women, presence of systemic diseases other than co-existing allergic rhinitis, asthma and atopic dermatitis and those with any documented history of hypersensitivity to the said drugs were excluded from the study.

A total of 67 patients were enrolled as per convenience sampling according to the inclusion and exclusion criteria and informed consent was obtained. Seven patients dropped out of the study and 30 patients from each group were included in the study (Group A received drug 0.1% olopatadine and Group B received 1.5% bepotastine besilate eye drops).

Clinical resolution of symptoms and signs in patients of VKC was observed over a period of 4 weeks. This study compared the efficacy and safety of both drugs in a pragmatic setting. Prescribing pattern and follow-up of patients was done as per routine clinical practice.

Patients on their first visit (baseline, day 0) were asked to sign the informed consent. A complete ophthalmic evaluation comprising visual acuity (Snellen chart), slit-lamp biomicroscopy, intraocular pressure and fundoscopy under pupillary dilatation was done. Patients fulfilling eligibility criteria were included in the study. Patients on their first visit (day 0) were examined and all the symptoms and signs were recorded on the pro forma.

The symptoms recorded were itching, lacrimation, foreign body sensation, photophobia and discharge. The patients were asked to scale on 0, 1, 2 and 3 scoring system.[10] The score of all individual symptoms and total subjective symptom score at each follow-up visit were recorded for both Group A and B [Table 1].
Table 1: Mean score of symptoms and total symptom score in patients with vernal keratoconjunctivitis during the study period (Group A and B)

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The signs of VKC were assessed under the headings of conjunctival hyperaemia, tarsal conjunctival papillary hypertrophy, limbal infiltration, punctate keratitis and Trantas dots. The scoring was done on a scale on 0, 1, 2 and 3 scoring system. The score of all individual signs and total objective sign score at each follow-up visit were recorded for both Group A and B [Table 2].
Table 2: Mean score of signs and total sign score in patients with vernal keratoconjunctivitis during the study period (Group A and B)

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Any other ocular or oral anti-allergic drugs with the exception of preservative-free artificial tears and cold compresses were discontinued in the 28-day study period during which the symptoms and signs of the patients were scored. No oral corticosteroid was allowed. All the above parameters were reassessed on day 14 (visit 2) and day 28 (visit 3). All these visits were as per the standard of care of the patient.

Statistical analysis

Data were entered into MS EXCEL spreadsheet and analysis was done using IBM Statistical Package for Social Sciences, Windows version 23.0 (IBM Corp., Armonk, N.Y., USA). Categorical variables were presented as proportion with confidence interval (CI) and continuous variables were presented as mean ± standard deviation and median. Statistical tests applied were as follows:

As we had nonparametric data, Wilcoxon rank-sum test (Mann–Whitney U-test) was used to compare the two groups in terms of symptom and sign score at each of the time points.

Friedman test was used to explore the change in score over time within each group.

The generalised estimating equation method was used to explore the difference in change in score between the two groups over time. P <0.05 was considered statistically significant.


  Results Top


The mean age of Group A was 19.37 ± 10.80. The mean age in Group B was 19.40 ± 9.98. There was no significant difference between the groups in terms of age (years) (P = 0.888). Out of 60 patients, 39 (65%) were male and 21 (35%) were female in our study. In Group A, 56.7% of the patients were male and 43.3% were female. In Group B, 73.3% of the patients were male and 26.7% were female. There was no significant difference between the various groups in terms of distribution of gender (P = 0.176).

There was a statistically significant difference between the two groups (P < 0.001) in terms of change in subjective score total from the baseline time point to the 2-week follow-up and 4-week follow-up, with olopatadine showing mean of change as −8.90 ± 1.52 as compared to bepotastine with mean of change −6.97 ± 1.33 at the end of 4 weeks [Figure 1]. On comparison of change between the two groups, there was a significant difference in the lacrimation score, Foreign body sensation score and discharge score and no significant difference in the trend of itching (P = 0.037) and photophobia score (P = 0.464). For olopatadine, 95% CI of absolute change of subjective score total at the end of 4 weeks from baseline was − 11.88 to −5.92 and for bepotastine, it was −9.58 to −4.36.
Figure 1: Distribution of subjective score total at baseline, 2-week follow-up and 4-week follow-up time points

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The two groups differed significantly (P < 0.001) in terms of change in objective score total from the baseline time point to the 2-week and 4-week follow-up, with olopatadine showing mean of change as −6.87 ± 1.38 as compared to bepotastine with a mean of change-5.07 ± 1.28 at the end of 4 weeks [Figure 2]. On comparison of change between the two groups, there was a significant difference in the trend of tarsal papillae score and conjunctival hyperaemia score over time in both the groups (P < 0.001). There was no significant difference in the trend of limbal infiltration score (P = 0.163), punctate keratitis score (P = 0.199) and trantas dots score (P = 0.053) over time in both the groups. For olopatadine, 95% CI of absolute change of objective score total at the end of 4 weeks from baseline was −9.57–−4.17 and for bepotastine, it was −7.58–−2.56.
Figure 2: Distribution of objective score total at baseline, 2-week follow-up and 4-week follow-up time points

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  Discussion Top


In the current study, treatment with both topical 0.1% olopatadine eye drops and 1.5% bepotastine besilate eye drops was found to be effective for patients with VKC. Topical olopatadine of various concentrations has been investigated for various forms of allergic conjunctivitis. Abelson[11] studied olopatadine eye drops of various concentrations (0.01%, 0.05%, 0.1% or 0.15%) in one eye and placebo in the other and found that all the above four concentrations of olopatadine were clinically and statistically better than placebo in preventing ocular itching and the 0.1% concentration was found to be most effective.

A prospective study was performed in 50 eyes of 25 patients by Corum et al.[12] between December 2002 and April 2003 on the drug olopatadine 0.1%, it was noted that at the end of the 2-month treatment period, all symptoms evidenced a statistically significant improvement: itching (P = 0.03); tearing (P = 0.01); hyperaemia (P = 0.03); foreign-body sensation (P = 0.006); visual disturbance (P = 0.035) and burning (P = 0.002), except for photophobia (P = 0.07).

In our study too, when the overall change in photophobia score over time was compared in the two groups, there was no significant difference in the trend of photophobia score over time in both the groups (P = 0.464). In the same study by Corum et al., clinical signs also showed a statistically significant improvement: Mucus discharge (P = 0.008); upper tarsal conjunctiva hyperaemia (P = 0.025); mucus discharge on upper tarsal conjunctiva (P = 0.025); bulbar conjunctival swelling (P = 0.046); limbal conjunctival hyperaemia (P = 0.003) and corneal involvement (P = 0.038). The treatment was not effective for limbal papillae (P = 1). In the present study, the overall change in limbal infiltration score over time when compared in the two groups did not show any significant difference over time in both the groups (P = 0.163).

Topical bepotastine of 1% and 1.5% concentrations have been investigated for various forms of allergic conjunctivitis.

In a study by Bergmann et al. in 2014, two Phase III, placebo-controlled, double-masked, randomised clinical trials were conducted at a total of six separate centres using the Conjunctival allergen challenge (CAC) model of allergic conjunctivitis. A statistically significant reduction in ocular itching was observed for bepotastine besilate ophthalmic solution 1.5% treatment compared to placebo at all-time points (P < 0.0001).[13]

Another clinical trial evaluated the safety and effectiveness of bepotastine besilate ophthalmic solutions 1.0% and 1.5% compared with placebo for the treatment of ocular itching and conjunctival hyperaemia (redness) using the CAC model of allergic conjunctivitis when dosed 16 h before a CAC test. Both bepotastine besilate ophthalmic solution 1% and 1.5% demonstrated clinical effectiveness and statistical significance in comparison to placebo for the reduction in CAC-induced ocular itching 16 h after drug administration. Bepotastine besilate ophthalmic solution 1.5% was more effective than bepotastine besilate ophthalmic solution 1.0%.[14]

A randomised, observer-masked, single-centre, cross-over study comparing the efficacy of bepotastine besilate 1.5% ophthalmic solution versus olopatadine hydrochloride 0.2% ophthalmic solution evaluated by patient preference showed that bepotastine besilate offered significantly better relief of morning and evening itchy/running nose, evening ocular itch and relief of morning and evening ocular allergy symptoms than olopatadine 0.2%. About 66.7% of patients stated that they would prefer bepotastine besilate 1.5% over olopatadine hydrochloride 0.2% to treat allergic conjunctivitis.[8]

In our study, we compared the individual symptom score, total subjective symptoms score, individual sign score and total objective sign score at the 2-week and 4-week follow-up time points with each drug. The two groups differed significantly in terms of change in subjective score total from the baseline time point to the following time points: 2-week follow-up and 4-week follow-up, with olopatadine showing mean of change −8.90 ± 1.52 as compared to bepotastine with mean of change −6.97 ± 1.33 at the end of 4 weeks. On comparison of change between the two groups, there was a significant difference in the lacrimation score, foreign-body sensation score and discharge score and no significant difference in the trend of itching and photophobia score.

The two groups differed significantly (P < 0.001) in terms of change in objective score total from the baseline time point to the 2-week and 4-week follow-up, with olopatadine showing mean of change as −6.87 ± 1.38 as compared to bepotastine with mean of change −5.07 ± 1.28 at the end of 4 weeks [Figure 2]. On comparison of change between the two groups, there was a significant difference in the trend of tarsal papillae score and conjunctival hyperaemia score over time in both the groups (P < 0.001). There was no significant difference in the trend of limbal infiltration score, punctate keratitis score and trantas dots score over time in both the groups.

In this study, both the drugs olopatadine 0.1% eye drops and bepotastine besilate 1.5% eye drops significantly reduce symptoms and signs in patients of VKC. All patients showed marked improvement without developing significant side effects.

Limitations

The present study was observational and not a vigorously conducted randomised controlled clinical trial. It also had a small sample size (60) which cannot be extrapolated to a larger population. The duration of the study is less (4-week follow-up). Increased follow-up visits would yield better outcome evaluation.


  Conclusion Top


Through this study, we inferred that both topical 1.5% bepotastine besilate twice daily and topical olopatadine 0.1% twice daily significantly reduce the symptoms and signs of VKC over a 4-week follow-up period. However, the two groups differed significantly in terms of total subjective symptom score and total objective sign score at the 2-week and 4-week follow-up, with olopatadine 0.1% being more efficacious than 1.5% bepotastine besilate.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Collum MT. Vernal keratoconjunctivitis. Acta Ophthalmol Scand 1999;228:14-6.  Back to cited text no. 1
    
2.
Leonardi A, Busca F, Motterle L, Cavarzeran F, Fregona IA, Plebani M, et al. Case series of 406 vernal keratoconjunctivitis patients: A demographic and epidemiological study. Acta Ophthalmol Scand 2006;84:406-10.  Back to cited text no. 2
    
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De Smedt S, Wildner G, Kestelyn P. Vernal keratoconjunctivitis: An update. Br J Ophthalmol 2013;97:9-14.  Back to cited text no. 3
    
4.
Friedlaender MH. Allergy and Immunology of the Eye. Hagerstown: Harper and Row; 1979. p. 185-8.  Back to cited text no. 4
    
5.
Sandford-Smith JH. Vernal eye disease in Northern Nigeria. Trop Geogr Med 1979;31:321-8.  Back to cited text no. 5
    
6.
Baryishak YR, Zavaro A, Monselise M, Samra Z, Sompolinsky D. Vernal keratoconjunctivitis in an Israeli group of patients and its treatment with sodium cromoglycate. Br J Ophthalmol 1982;66:118-22.  Back to cited text no. 6
    
7.
Tuft SJ, Cree IA, Woods M, Yorston D. Limbal vernal keratoconjunctivitis in the tropics. Ophthalmology 1998;105:1489-93.  Back to cited text no. 7
    
8.
Namdar R, Valdez C. Alcaftadine: A topical antihistamine for use in allergic conjunctivitis. Drugs Today (Barc) 2011;47:883-90.  Back to cited text no. 8
    
9.
Williams JI, Kennedy KS, Gow JA, Torkildsen GL, Abelson MB, Gomes PJ, et al. Prolonged effectiveness of bepotastine besilate ophthalmic solution for the treatment of ocular symptoms of allergic conjunctivitis. J Ocul Pharmacol Ther 2011;27:385-93.  Back to cited text no. 9
    
10.
Bleik JH, Tabbara KF. Topical cyclosporine in vernal keratoconjunctivitis. Ophthalmology 1991;98:1679-84.  Back to cited text no. 10
    
11.
Abelson MB. Evaluation of olopatadine, a new ophthalmic antiallergic agent with dual activity, using the conjunctival allergen challenge model. Ann Allergy Asthma Immunol 1998;81:211-8.  Back to cited text no. 11
    
12.
Corum I, Yeniad B, Bilgin LK, Ilhan R. Efficiency of olopatadine hydrochloride 0.1% in the treatment of vernal keratoconjunctivitis and goblet cell density. J Ocul Pharmacol Ther 2005;21:400-5.  Back to cited text no. 12
    
13.
Bergmann MT, Williams JI, Gomes PJ. Treatment of allergic conjunctivitis with bepotastine besilate ophthalmic solution 1.5%. Clin Ophthalmol 2014;8:1495-505.  Back to cited text no. 13
    
14.
Macejko TT, Bergmann MT, Williams JI, Gow JA, Gomes PJ, McNamara TR, et al. Multicentre clinical evaluation of bepotastine besilate ophthalmic solutions 1.0% and 1.5% to treat allergic conjunctivitis. Am J Ophthalmol 2010;150:122-7.  Back to cited text no. 14
    


    Figures

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