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 Table of Contents    
Year : 2020  |  Volume : 52  |  Issue : 6  |  Page : 476-481

To evaluate the efficacy and safety of olopatadine 0.1% ophthalmic solution and bepotastine 1.5% ophthalmic solution in patients with vernal keratoconjunctivitis in a tertiary care hospital

Department of Pharmacology, Osmania Medical College, Hyderabad, Telangana, India

Date of Submission22-Apr-2020
Date of Decision16-Sep-2020
Date of Acceptance04-Jan-2021
Date of Web Publication19-Feb-2021

Correspondence Address:
Dr. Resu Neha Reddy
Department of Pharmacology, Osmania Medical College, Turrebaz Road, Koti, Hyderabad - 500 095, Telangana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijp.IJP_174_20

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 » Abstract 

INTRODUCTION: Vernal conjunctivitis comprises 0.5% of allergic eye diseases. The study is intended to collate the effectiveness of drugs by observing the reduction in signs and symptoms.
OBJECTIVES: The objective of the study is to evaluate the effectiveness and safety of olopatadine 0.1% ophthalmic drops with bepotastine besilate 1.5% ophthalmic drops in patients with vernal keratoconjunctivitis (VKC).
MATERIALS AND METHODS: A randomized, open-label, comparative study conducted in Sarojini Devi Eye Hospital, Telangana. The study included 50 patients diagnosed with VKC, of which Group A and Group B were given olopatadine 0.1% ophthalmic drops and bepotastine besilate 1.5% ophthalmic drops, respectively, twice a day for 8 weeks. The reduction in signs and symptoms in both groups was compared. The observations and results were tabulated accordingly, and data were analyzed using the SPSS. The unpaired t-test is used as the test of significance in between two groups. P value is statistically significant when it is less than 0.05.
RESULTS: Overall, 50 cases were included in the study, 72% of total patients were in the age group of 5–10 years, and 28% were in the age group of 11–15 years. There were 39 males and 11 females. After 8 weeks of follow-up, the mean reduction in the scoring of symptoms and signs provided better and quicker relief of watering, ocular discomfort, and conjunctival hyperemia with bepotastine 1.5% eye drops. Olopatadine 0.1% eye drops provided faster improvement in papillary hypertrophy. Both drugs were equally effective in reducing itching. Laboratory findings of absolute eosinophil count had no statistical significance in between the two groups.
CONCLUSIONS: In this study, based on the evaluation of therapeutic performance, bepotastine eye drops proved quicker relief of symptoms and signs compared to olopatadine eye drops but was not statistically significant which would prove beneficial for the patients.

Keywords: Absolute eosinophil count, allergy, bepotastine, olopatadine, vernal keratoconjunctivitis

How to cite this article:
Sruthi V, Reddy RN, Sowmini K, Grace NS. To evaluate the efficacy and safety of olopatadine 0.1% ophthalmic solution and bepotastine 1.5% ophthalmic solution in patients with vernal keratoconjunctivitis in a tertiary care hospital. Indian J Pharmacol 2020;52:476-81

How to cite this URL:
Sruthi V, Reddy RN, Sowmini K, Grace NS. To evaluate the efficacy and safety of olopatadine 0.1% ophthalmic solution and bepotastine 1.5% ophthalmic solution in patients with vernal keratoconjunctivitis in a tertiary care hospital. Indian J Pharmacol [serial online] 2020 [cited 2023 Oct 1];52:476-81. Available from: https://www.ijp-online.com/text.asp?2020/52/6/476/309722

 » Introduction Top

Allergies are the fifth leading cause of the world's chronic illnesses, affecting 40% of the population.[1] Globally, in the last 10 years, there has been a drastic increase in allergic diseases. The occurrence of allergic diseases among children is rising moderately in between 0.3% and 20.5%. There are so many causative factors such as genetics, pets, air pollution, and early childhood exposure being the reasons for this increase.[2] Among the causes of ocular morbidity in India, allergic conjunctivitis is at the second position and involves about 15%–20% of people attending ophthalmology clinic. School absenteeism in children is common because of its distressing symptoms.[3]

Allergic conjunctivitis includes persistent allergic conjunctivitis, seasonal allergic conjunctivitis (SAC), vernal keratoconjunctivitis (VKC), and atopic keratoconjunctivitis. SAC is about 25%–50% of cases.[4] VKC constitutes 0.5% of allergic diseases in eye.[5] VKC occurs most frequently in the male population belongs to warm, dry, subtropical areas such as Japan, India, Thailand, South America, Mediterranean, Central, Middle East, and Western Africa. Most common VKC seen in dark-skinned African and Indian population is limbal form. The prevalence for Western Europe was 3.2 in 10,000, whereas a higher prevalence ranging from 2.4 to 27.8 in 10,000 was seen in Italy, a country with a Mediterranean climate.[6]

VKC is a persistent, bilateral, occasionally asymmetric, cyclically worsened, allergic ocular surface inflammation that includes bulbar and/or tarsal conjunctiva. VKC is characterized by giant papillae seen in both upper tarsal conjunctiva or at the limbus.[7] It is an IgE- and T cell-mediated condition, progressing to a chronic inflammatory conjunctival allergic response involving eosinophil, lymphocyte, and structural cell activation. New antihistamines that combine stabilizing properties of the mast cells with antagonism to histamine receptors such as olopatadine, bepotastine, alcaftadine, azelastine, epinastine, and ketotifen are currently available.

Olopatadine hydrochloride is a second-generation antihistamine (as well as anticholinergic and mast cell stabilizer) that exerts comprehensive pharmacological actions such as histamine H1 receptor antagonism, chemical mediator suppression, tachykinin release inhibitory action, and eosinophil infiltrative suppression.[8],[9] During 1996 and 2002, olopatadine ophthalmic solution was approved for the treatment of SAC and chronic allergic conjunctivitis in the USA and the European Union, respectively. In India, olopatadine 0.1% ophthalmic drops with the trade name of Pataday or Olopat, which is used for once or twice-daily regimen in severe cases of allergic conjunctival diseases.[10] In animal studies and clinical trials, olopatadine ophthalmic solution proved to be a safe and efficacious medicament in SAC and perennial allergic conjunctivitis. Drug successfully alleviates itching, redness, edema, watering, and nasal allergic symptoms.[11] In rats and rabbits, olopatadine was established to be not having any teratogenic potential. This drug should be used in pregnant women cautiously, considering risk–benefit ratio, as there are no abundant and controlled trials in pregnant women. Olopatadine was detected after oral administration in nursing rat milk. There is no evidence for sufficient systemic absorption with topical ocular administration, so caution should be exercised. In patients below the age of 2 years, safety and efficacy have not yet been established.

Bepotastine is a second-generation nonsedating antihistamine with diverse mechanisms being appropriately investigated in both animal studies and clinical trials. The US Food and Drug Administration accepted its use in the management of allergic conjunctivitis, with the dose of twice daily in patients 2 years of age and above in 2009.[12] It is a double-acting agent with both extremely selective histamine H1 receptor antagonism and mast cell-stabilizing effects. It exerts anti-inflammatory actions by inhibiting leukotriene B and improving eosinophilic chemotaxis and activation.[13] Topical bepotastine has been used to treat ocular itching, conjunctival erythema, and other signs and symptoms associated with allergic conjunctivitis. There is no availability of human studies for use of bepotastine during pregnancy causing any side effects or complications. The developmental and health advantages of breastfeeding, along with the therapeutic need of the mother for bepotastine, should be considered. In patients under 2 years of age, the safety and effectiveness of bepotastine besilate ophthalmic solution 1.5% were not identified. A study by Okubo et al. has established that bepotastine besilate is effective and safe for perennial allergic rhinitis patients aged 7–15 years.[14]

Being a chronic condition, prudent use of medicament is needed because drug treatment is prolonged and frequent. There were only minimal research studies done in VKC by comparing efficacy and safety of 0.1% olopatadine and 1.5% bepotastine in India. Our study is intended to compare the effectiveness and safety of olopatadine 0.1% ophthalmic drops and bepotastine besilate 1.5% ophthalmic drops with BD administration to relieve the symptoms of VKC.

 » Materials and Methods Top

The study was done in the Outpatient Department of Ophthalmology in Sarojini Devi Eye Hospital, Hyderabad, for duration of 6 months from July 2019 to December 2019. Institutional ethics committee approved the study (Reg. No. ECR/300/Inst/AP/2013/RR-19). For participants above 18 years of age, written informed consent was taken in an authorized format in local language after describing all study procedures and course of action. For participants less than 18 years of age, their parents or guardians were explained the procedures, and written informed consent was attained. For illiterate people, left thumb mark was taken. After acquiring informed consent from all participants, the analytical details of 59 patients including past and present history and clinical and slit-lamp examination of eyes performed were entered. Diagnosis for VKC was made by an ophthalmologist. Following the screening of 59 patients, 50 patients were enlisted in the study who fit into inclusion and exclusion criteria.

Inclusion criteria

  1. Clinically diagnosed with VKC by an ophthalmologist
  2. Patients with the age group of 5–25 years.
  3. Patients who can adherent to follow-up schedule.

Exclusion criteria

  1. Age less than 5 years
  2. Contact lens wearer during the period of study
  3. Patients with active ocular infections and pathological conditions
  4. Patients with ocular disorders such as pterygium, dry eyes, and ophthalmic conditions such as uveitis or glaucoma
  5. History of ocular surgery in 3 months.

By simple randomization (odd/even number) method, registered patients were grouped into A and B. Group A and Group B were given olopatadine 0.1% ophthalmic drops and bepotastine besilate 1.5% ophthalmic drops, respectively, administered one drop in the affected eye twice daily for 8 weeks.

The ocular signs such as conjunctival hyperemia and papillary hypertrophy were evaluated. The gradings were given according to the severity of signs (absence of signs as grade 0, mild signs as grade 1, moderate signs as grade 2, and severe signs as grade 3). Ocular symptoms such as itching, discomfort, and watering were estimated by discussing with the patients, and grading was given depending on severity (absence of signs as grade 0, mild signs as grade 1, moderate signs as grade 2, and severe signs as grade 3). During the study, none of the patients were lost to follow-up.

Statistical analysis

The observations and results were tabulated accordingly and data were analyzed using the SPSS Version 16, IBM, Chennai, Tamil Nadu, India. The unpaired t-test is used as the test of significance in between two groups. P value is statistically significant when it is less than 0.05.

 » Results Top

Among 50 patients, 36 patients (72%) are in the range of 5–10 years, and 14 patients (28%) are in the range of 11–15 years. The age distribution of the study population is shown in [Figure 1]. Of 50 patients included in the study, 39 (78%) patients were male and 11 (22%) patients were female as shown in [Figure 2]. [Table 1] shows mean itching scores during each visit. The itching scores among the treatment groups with all follow-ups compared with baseline are not statistically significant (P > 0.05). [Table 2] shows the mean ocular discomfort scores during each visit. At the 1st, 2nd, and 3rd follow-up, there is statistical significance in ocular discomfort scores with Group B (P < 0.05). [Table 3] shows the mean watering scores during each visit. In Group B, during the 2nd, 3rd, and 4th follow-ups, there is statistical significance in watering scores (P < 0.05). [Table 4] shows the mean conjunctival hyperemia scores during each visit. During 1st, 2nd, and 3rd follow-ups, there is statistical significance in conjunctival hyperemia scores with Group B (P < 0.05). [Table 5] shows the mean papillary hypertrophy scores during each visit. During the 2nd, 3rd, and 4th visits, there is statistical significance in papillary hypertrophy scores with Group A (P < 0.05). [Figure 2] shows the absolute eosinophil count (AEC) levels between treatment groups. Before and after the treatment, there is no statistical significance in reduction of AEC levels.
Figure 1: Age and gender distribution

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Figure 2: Changes in the levels of absolute eosinophil count between treatment groups

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Table 1: Mean itching scores during each visit

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Table 2: Mean ocular discomfort scores during each visit

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Table 3: Mean watering scores during each visit

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Table 4: Mean conjunctival hyperaemia scores during each visit

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Table 5: Mean papillary hypertrophy scores during each visit

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Very minimal patients complained of adverse events during the study. In Group A, two patients had headache, and in Group B, three patients encountered headache and one had sinusitis.

 » Discussion Top

VKC is a bilateral, long-term, cyclical allergic ocular inflammation which affects bulbar or tarsal conjunctiva. Children and young adults with an atopic history are more prone to VKC.[15] It commonly affects people with history of allergic conditions such as seasonal allergy, bronchial asthma, or eczema.[16] VKC has a wide geographic distribution. Young males are primarily affected in the dry and hot climates.[17] It is prevailing in Mediterranean temperate zones, Western Africa, Middle East, Japan, Indian subcontinent, and South America.[18] 49% of VKC patients show familial history of allergic conditions such as asthma, rhinitis, eczema, urticaria, and multiple atopic diseases.[19] Among them, asthma is the most frequently seen allergic disorder in VKC.[20] Other inflammatory diseases, such as psoriasis and thyroiditis, may be associated with a family history.[21],[22] It has a major impact on day-to-day life and performance in school-going children.

The present research was conducted in an attempt to determine which agent would help regulate the symptoms of VKC in our patient population. It is very important to understand the fundamental mechanisms in allergy and selection of the right medication. Olopatadine found to be effective in VKC.[23],[24] Bepotastine is a less commonly used drug.[25],[26] In this review, we seek to assess the two medications and evaluate their effectiveness in treating Spring Catarrh. For this study, different signs and symptoms of VKC were used as criteria for assessment.[27] This is a randomized open-label study in which the patients diagnosed with VKC who attended ophthalmic outpatient department divided into Group A and Group B. Group A patients were given olopatadine 0.1% twice a day for 8 weeks, and Group B patients were given bepotastine besilate 1.5% twice a day for 8 weeks. Olopatadine which is commonly used compared with Bepotastine for efficacy, safety, and tolerability. In the present study, out of 59 patients who were screened, 50 patients were included in the study, randomized to Group A and Group B, each including 25. During the study period, none of the patients have not missed their follow-ups.

In a study done by McCabe and McCabe, bepotastine when compared to olopatadine showed a significant reduction in ocular itching and no significance between the comfort ratings.[10] A study between 0.1% olopatadine, 1.5% bepotastine, and 0.25% alcaftadine worked similarly in relief of mild-to-moderate allergic conjunctivitis symptoms, after 1 week of treatment.

For allergic conjunctivitis, 0.2% olopatadine and 1.5% bepotastine eye drops are safe and well-tolerated topical medications.[28],[29] In a study done by Hida et al., a comparison between 0.1% olopatadine hydrochloride and 0.025% ketotifen fumarate in VKC between the baseline and the 2nd visit, olopatadine treatment resulted in decreased burning, but ketotifen was slightly better after 4th visit. Papillae and Horner-trans dots in both classes were not significantly different.

In our study, during initial follow-ups on days 7, 21, and 35, bepotastine showed significant reduction in symptoms such as ocular discomfort, watering, and capillary hyperemia, suggesting the faster onset of action. Olopatadine showed marked reduction in papillary hypertrophy. After 8 weeks of treatment, both drugs were uniformly efficacious in reducing signs and symptoms of VKC. Studies with different attributes such as larger sample size, double masking, and patient preference and studies at different geographical locations and during different seasons of the year are needed for better definition of therapy in VKC.

 » Conclusions Top

In this study, although bepotastine altered the natural course with quicker onset of action at the end of the 8th week, both drugs are equally effective in reducing the signs and symptoms. Bepotastine proved quicker to relieve watering, ocular discomfort, and conjunctival hyperemia. Olopatadine provided faster improvement in papillary hypertrophy. Laboratory findings had no statistical significance between 0.1% olopatadine and 1.5% bepotastine in improving the AEC of the VKC patients. Being more commonly prescribed of the two drugs, olopatadine is readily available at the pharmacy store. Bepotastine, on the other hand, was available at a few selected retail outlets and was costlier. Researches with above-mentioned attributes can be done in the future.


The authors thank Dr. T. Chakradhar, Professor and Head, Department of Pharmacology, for expert advice. We also thank Dr. Santha Sheela Kumari for statistical help. We wish to express our gratitude to the patients of Sarojini Devi Eye Hospital for their cooperation.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 » References Top

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  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

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