202 Vol. 29, No. 4, Oct – Dec, 2013 Pakistan Journal of Ophthalmology Original Article Comparison between Topical Olopatadine Hydrochloride 0.1% and Ketotifen Fumarate 0.025% for the Relief of Symptoms of Vernal Keratoconjunctivitis (VKC) Muhammad Rizwan Khan, Muhammad Naeem Azhar, Muhammad Sufyan Aneeq Ansari, Tariq Mahmood Arain, Zaheer Uddin Aqil Qazi Pak J Ophthalmol 2013, Vol. 29 No. 4 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . See end of article for authors affiliations …..……………………….. Correspondence to: Muhammad Rizwan Khan Bahawal Victoria Hospital Bahawalpur …..……………………….. Purpose: To compare the topical administration of Olopatadine HCL 0.1 % and Ketotifen fumarate 0.025% for the relief of symptoms of VKC. Material and Methods: From April 2010 to September 2010, this randomized controlled trial was conducted on 120 diagnosed patients of VKC from out-door patient department of Bahawal Victoria Hospital Bahawalpur, equally and randomly enrolled in two groups. In group A patients were given topical Olopatadine HCL 0.1% QID and in group B topical Ketotifen fumarate 0.025% QID. Regular follow up of all the patients were done for relief of symptoms on day 0, 7 and 28. Final outcome was determined at the end of 4 th week from start of the treatment. Results: All 120 patients completed the study with regular follow up. Patients presented with multiple symptoms and clinical types of VKC. All the patients felt early and significant relief in their symptoms, but the effectiveness and tolerability of Olopatadine HCL 0.1% was significantly more (P<0.05) as compared to ketotifen fumarate 0.025%. Conclusion: Both topical Olopatadine HCL 0.1% and ketotifen fumarate 0.025% are effective in treating the VKC. However, Olopatadine HCL 0.1% provides greater symptomatic relief in patients of VKC as compared to Ketotifen fumarate 0.025%. cular allergies are the most common conditions affecting the external ocular adnexa throughout the world1. These allergies are type 1 hypersensitivity reactions mediated by Ig-E in response to various environ- mental allergens such as pollens, mites, molds, dust, grass, weeds and animals dander2,3. Vernal Keratoconjunctivitis (VKC) is a bilateral, recurrent allergic conjunctivitis affecting the children and young adults in 5-15 years age group usually2. VKC rarely persists till puberty2. VKC is associated with genetic predisposition, history of atopy and non- specific hypersensitivity. VKC is an Ig-E and cell- mediated immune response in the conjunctival mucosa to exogenous allergens2. It usually occurs at the onset of hot weather (spring season) and subsides during winter2. Seasonal recurrences with exacerba- tions and remissions are common2. Symptoms of VKC consist of: intense itching, lacrimation, redness, foreign body sensation, photophobia, thick mucoid discharge2. The clinical signs of VKC on slit lamp examination are; conjunctival hyperemia, chemosis, papillary hypertrophy, macro papillae, gelatinous thickening of limbal conjunctiva and punctuate epithelial erorions2. Conjunctival mast cells play the main role in the pathophysiology of VKC. When a specific allergen O COMPARISON BETWEEN TOPICAL OLOPATADINE HYDROCHLORIDE 0.1% AND KETOTIFEN FUMARATE 0.025% Pakistan Journal of Ophthalmology Vol. 29, No. 4, Oct – Dec, 2013 203 binds to the sensitized mast cells in the conjunctiva, degranulation of the mast cells and release of inflammation mediators such as histamine, eosinophilic chemotactic factor, prostaglandins, Leukotrienes, platelet activating factors occur1,2. These inflammatory mediators predominantly histamine are responsible for symptoms of VKC1,2. The main clinical types of VKC are: Palpebral, Limbal, Mixed, Corneal disease or keratopathy1,2,8. The rationale of the study is to compare the effectiveness of Olopatadine HCL 0.1% and Ketotifen fumarate 0.025% for the relief of symptoms of VKC. MATERIAL AND METHODS From April 2010 to September 2010, this randomized controlled trial was conducted on 120 diagnosed patients of VKC from out-door patient department of Bahawal Victoria Hospital Bahawalpur, equally and randomly enrolled in two groups. 120 patients included in the study, 62 were male and 58 patients were female. The age varied from 5-20 years in both groups. Mean age of the patients was 9.10 ± 3.90 years. In group A patients were given topical Olopatadine HCL 0.1% Qid and in group B topical Ketotifen fumarate 0.25% Qid. Regular follow up of all MUHAMMAD RIZWAN KHAN, et al 204 Vol. 29, No. 4, Oct – Dec, 2013 Pakistan Journal of Ophthalmology the patients were done for relief of symptoms on day 0, 7 and 28. Final outcome was determined at the end of 4th week from start of the treatment. The efficacy of two drugs was determined by the relief of symptoms of VKC. Symptoms included in this study were; itching, redness, watering, foreign body sensation, photophobia. Relief of the symptoms was considered as resolution of disease. DATA ANALYSIS The collected data was entered and analyzed by using the SPSS version 10. The data was analyzed and presented in univariate and bivariate tables. For categorical variables like gender, frequencies & percentages were presented. Effect modifiers like age & gender were controlled to observe the effect on outcome between two groups. The level of statistical significance was p <0.05. Chi-Square Test was used as the test of significance to compare the proportion of relief of symptoms between the two groups. RESULTS All 120 patients were included in two study groups (each group consisting of 60 patients). Group A was treated with topical Olopatadine HCL 0.1% and the Group B was treated with topical ketotifen fumarate 0.025%. Among 120 patient included in the study, 62 were male and 58 patients were female. The age varied from 5-20 years in both groups. Mean age of the patients was 9.10 ± 3.90 years. All patients completed the study and came for follow up. Drug compliance was very good among the patients and they followed the directions very well. All the patients were followed up until the resolution of their complaints of allergy (Table 1). Patients presented with multiple symptoms and clinical types of VKC. All the patients felt early and significant relief in their symptoms, but the effectiveness and tolerability of Olopatadine HCL 0.1% was significantly more (P<0.05) from ketotifen fumarate 0.025% (Table 2). DISCUSSION Ocular allergies affects more than 20% of the world’s population and impairs their daily activities. The number of ocular allergy symptoms is increasing day by day along with the environmental pollution. Allergic conjunctivitis hampers the quality of life. The goal of treatment of VKC is to rapidly and effectively resolve the clinical signs and symptoms and improve the quality of life. As the mast cells degranulation and release of Histamine and other inflammatory mediators is the main event in the ocular allergic cascade, so the aim of treatment of VKC is to antagonize the histamine activity and to maintain stability of mast cells. The pharmacotherapy of allergic conjunctivitis consists of several classes of drugs, antihistamines, mast cells stabilizers, dual acting agents, NSAIDS and steroids2,6,8. Ketotifen is a mast cell stabilizer with inhibitory effects upon the release of inflammatory mediators and eosinophilic chemotaxis. It has been shown to offer great efficacy in controlling the symptoms of VKC. It is the only drug available in unit dose form without preservatives. Olopatadine in turn possess dual action and better tolerability7,8. In this study Olopatadine HCL 0.1% and Ketotifen fumarate 0.025% ophthalmic solutions were instilled as a dose of 1 drop QID in two sets of 60 patients each and their effects in relieving the symptoms of VKC were studied and compared. This study showed that Olopatadine was significantly more effective and well tolerated as compared to ketotifen. This study also revealed that Olopatadine is significantly more effective (p<0.05) against symptoms of VKC as compared to ketotifen after four weeks. This is the first comparative study between 0.1% Olopatadine and 0.025% ketotifen in treatment of vernal keratoconjunctivitis in Pakistan. The results of our study favour the Olopatadine for treatment of VKC. The use of Olopatadine provides quick recovery to eyes suffering from VKC with no apparent risk of side effects. As this study was conducted on a limited number of patients and was a single centre trial, so further prospective interventional multicentered placebo controlled trials may be needed for better assessment of efficacy and safety of these new treatment modalities in management of VKC. CONCLUSION Both topical Olopatadine HCL 0.1% and ketotifen fumarate 0.025% are effective in treating the VKC. However, Olopatadine HCL 0.1% provides greater symptomatic relief in patients of VKC as compared to Ketotifen fumarate 0.025%. COMPARISON BETWEEN TOPICAL OLOPATADINE HYDROCHLORIDE 0.1% AND KETOTIFEN FUMARATE 0.025% Pakistan Journal of Ophthalmology Vol. 29, No. 4, Oct – Dec, 2013 205 Author’s Affiliation Dr. Muhammad Rizwan Khan Medical Officer Bahawal Victoria Hospital Bahawalpur Dr. Muhammad Naeem Azhar Ophthalmologist LRBT Free Eye Hospital Lahore Dr. Muhammad Sufyan Aneeq Ansari RMO LRBT Free Eye Hospital Lahore DR. Tariq Mahmood Arain Associate Professor Bahawal Victoria Hospital Bahawalpur Dr. Zaheer uddin Aqil Qazi Chief Consultant Ophthalmologist LRBT Free Eye Hospital Lahore REFERENCES 1. Katelaris CH. Ocular allergy: implications for the clinical immunologist. Ann Allergy Asthma – Immunol. 2003; 90: 23-7. 2. Kanski JJ. Clinical ophthalmology: A systematic approach, 7th edition Butterworth Heinemann Elsevier; 2011; 200-1. 3. Avunduk AM, Tekelioglu Y, Turk A, Akyol N. Comparison of the effects of ketotifen fumarate 0.025% and olopatadine HCl 0.1% ophthalmic solutions in seasonal allergic conjunctivities: a 30 – day, randomized, double-masked, artificial tear substitute – controlled trial. Clin Ther. 2005; 27: 1392-402. 4. Greiner JV, Mundorf T, Dubiner H, Lonsdale J, Casey R, Parver L, et al. Efficacy and safety of ketotifen fumarate 0.025% in the conjunctival antigen challenge model of ocular allergic conjunctivitis. Am J Ophthalmol. 2003; 136: 1097-105. 5. 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