|Year : 1997 | Volume
| Issue : 3 | Page : 177-180
Topical ketorolac 0.5% solution for the treatment of vernal keratoconjunctivitis
A Sharma, R Gupta, J Ram, A Gupta
Department of Ophthalmology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Department of Ophthalmology, Postgraduate Institute of Medical Education and Research, Chandigarh
Source of Support: None, Conflict of Interest: None
The efficacy of topical ketorolac 0.5% in treatment of vernal keratoconjunctivitis (VKC) was evaluated in a randomised double-blind prospective trial in 21 patients. Ketorolac treated eyes showed 50.7% reduction in main symptoms of itching compared to 33.3% relief in placebo treated eyes after 2 weeks of treatment (p<0.01). Photophobia, ropy discharge, and conjunctival injection also lessened by 39.9%, 31.6%, and 39.1%, respectively, in ketorolac treated eyes compared to 23.8%, 17.3%, and 20.3% in placebo group. Transient stinging sensation was observed in 3 (14.3%) patients on ketorolac therapy. This study shows efficacy of ketorolac 0.5% solution in controlling symptoms in VKC.
Keywords: Vernal keratoconjunctivitis, ketorolac tromethamine, clinical trial
|How to cite this article:|
Sharma A, Gupta R, Ram J, Gupta A. Topical ketorolac 0.5% solution for the treatment of vernal keratoconjunctivitis. Indian J Ophthalmol 1997;45:177-80
Vernal keratoconjunctivitis (VKC) is an allergic ocular disorder primarily affecting children. The peak incidence of vernal conjunctivitis is between 11 to 13 years of age. Symptoms of VKC usually persist despite treatment. Topical vasoconstrictors alone or in combination with antihistamines, cromolyn sodium, topical corticosteroids and systemic antihistamines have been advocated for the treatment of VKC. Vasoconstrictors alone or in combination with antihistamines provide short term and inadequate symptomatic relief. Topical corticosteroids remain the mainstay of therapy. However prolonged use of steroids may result in glaucoma, cataract, dry eye and secondary infections. Serious side effects seen with steroids and incomplete amelioration of symptoms with the use of vasoconstrictors and antihistamines necessitated the study of efficacy of other therapeutic agents.
Ketorolac tromethamine is a new nonsteroidal antiinflammatory drug that blocks the cyclo-oxygenase enzyme that catalyzes the conversion of arachidonic acid to prostaglandins. The efficacy and safety of ketorolac tromethamine 0.5% solution has not been widely evaluated in the treatment of VKC though this drug has been used in other ocular inflammatory conditions. Ketorolac tromethamine has been evaluated and found effective in controlling postoperative inflammation following cataract surgery.In this study, we evaluated efficacy of topical ketorolac tromethamine 0.5% solution in VKC.
| Materials and Methods|| |
This prospective trial, carried out as a double-masked paired comparison study evaluates the efficacy and safety of ketorolac 0.5% solution for the treatment of VKC. VKC was diagnosed on the basis of itching, ropy discharge, presence of papillae in upper tarsal conjunctiva and limbal changes. All patients underwent complete ophthalmic examination including record of details of symptoms, visual acuity, slit lamp biomicroscopy and direct ophthalmoscopy. Presence of symptoms such as itching, swollen eyes, ropy discharge, photophobia, burning and foreign body sensation were recorded and graded according to the symptoms score scale. Patients were shown red, orange and green coloured pencils and were asked to pick up green for mild (score 1), orange for moderate (score 2), and red for severe (score 3) symptoms. Patients not having a particular symptom were ascribed score 0 for that symptom. The signs including lid edema, chemosis, conjunctival injection, discharge, papillae in upper tarsal conjunctiva, limbal hypertrophy and keratitis were also graded according to the signs severity scale [Table - 1]. Patients with dry eye detected on tear film examination and Schirmer test were excluded. Patients having allergic symptoms following use of drugs were also excluded. Prior treatment was stopped for one week before inclusion into the study. All patients were informed of the aim of the clinical trial.
Ketorolac 0.5% solution was prepared by adding 5 ml of normal saline to 1 ml ampoule of ketorolac tromethamine (30 mg/ml) injection. Six ml each of ketorolac (0.5%) solution and normal saline (placebo) were dispensed in identical vials. Coding of the vials was done by masked health personnel unassociated with the study. Both the ophthalmologist and the patients were masked to the nature of drug in each vial. One eye each of the 21 patients was randomly assigned to ketorolac and other to placebo. Both ketorolac and placebo drops were used 4 times a day for 2 weeks.
Symptoms and signs were assessed at baseline (day 0) and the scores were evaluated at day 7 and day 14 of treatment. Patient's complaints regarding use of drugs were recorded. After completion of the trial at two weeks, codes were revealed. Data obtained were analysed using unpaired Student's 't' test for within group and paired Student's 't' test for between treatment groups comparison.
| Results|| |
Twenty-one patients satisfied the inclusion criteria for this study. Sixteen patients were male and 5 female. The mean age of the patients was 14.7 years (range 5 to 38 years). These 21 patients included 6 of palpebral, 8 of limbal, and 7 of mixed form of VKC. Certain symptoms such as swollen eyes, burning, foreign body sensation and signs such as lid edema, chemosis, conjunctival mucus and keratitis were excluded from the analysis because of low base line scores (<0.75 mean or <25% of maximum score).
| Baseline scores|| |
The baseline symptom and sign scores in the ketorolac and placebo groups are shown in [Table - 2]. These scores between the two groups were not significantly different.
Symptoms. The mean scores for itching at day 7 and 14 were significantly lower than baseline in both ketorolac and placebo group (p<0.001). The mean scores for itching at day 7 and 14 were significantly lower in ketorolac group as compared to placebo group (p<0.001 and p<0.01, respectively).
The mean symptom scores for ropy discharge at day 7 and day 14 were significantly lower than at the baseline in ketorolac and placebo group (p<0.05). The mean scores for ropy discharge at day 7 and day 14 were lower in ketorolac group as compared to placebo, however, the difference was not statistically significant (p>0.05).
The mean scores for photophobia in ketorolac group at day 7 and day 14 were significantly lower (p<0.05) than at baseline. However, in placebo group, the mean scores for photophobia at day 7 and day 14 were not significantly different from baseline score (p>0.05).
Signs. Amongst signs, both ketorolac and placebo groups had significantly reduced conjunctival inflammation at day 7 and day 14. The mean scores at day 7 and 14 in ketorolac group were lower compared to the mean scores in placebo group though the difference was not statistically significant (p>0.05). No changes from baseline mean scores were found in both ketorolac and placebo group for papillary hypertrophy and limbal changes.
Overall, ketorolac 0.5% solution was effective in lessening the severity of itching (50.7%) ropy discharge (39.9%), photophobia (31.6%) and conjunctival injection (39.1%) from their onset after 2 weeks of therapy. The effect was less pronounced (33.3%, 23.8%, 17.3%, and 20.3%, respectively) in placebo treated eyes (Figure). Transient stinging sensation was observed by 3 patients (14.3%) in the ketorolac treated group.
| Discussion]|| |
VKC is a severe allergic conjunctivitis involving the conjunctiva and cornea. The condition is seen predominantly in children or young adults. Frequently they have history of other atopic diseases like eczema, asthma or hay fever. The main symptoms are severe itching and a tenacious stringy mucous discharge. The disease generally affects the upper tarsal conjunctiva with papillary hypertrophy and in severe cases cobble stone appearance is typical. The limbal conjunctiva may also be affected with gelatinous thickening. It is considered to be an atopic disease mediated by IgE antibodies (type I hypersensitivity reaction).
Ketorolac is a new non-steroidal anti-inflammatory (NSAID) drug that blocks the cyclooxygenase enzyme which catalyzes the conversion of arachidonic acid to prostaglandins.
Prostaglandins are believed to be the chemical mediators involved in the disease process. Ketorolac tromethamine 0.5% solution has been found effective in alleviating signs and symptoms of seasonal allergic conjunctivitis. [6,7] In the present study, ketorolac tromethamine 0.5% solution has been found safe and effective in the treatment of VKC. The treatment was effective in alleviating the prominent ocular symptoms of itching (p<0.001), discharge (p<0.05), and photophobia (p<0.05) both at day 7 and day 14 after initiation of therapy. Amongst the signs, conjunctival inflammation was reduced significantly (p<0.01) but other signs such as papillary hyperplasia and limbal changes showed little change. This is probably due to short duration of treatment in the present study. Because of high frequency of low average baseline scores larger changes from baseline for many allergic symptoms and signs could not be detected in either ketorolac or control treated eyes.
Studies have shown that a vehicle would act as an ocular wash and produce some relief of allergic symptoms and signs. A similar placebo effect was seen in our study. Normal saline has significantly reduced itching (p<0.001), ropy discharge (p<0.05) and conjunctival inflammation (p<0.05) both at day 7 and day 14 of study. However, ketorolac treated eyes consistently showed better response to allergic signs and symptoms throughout the treatment period. Ketorolac was more effective in reducing the prominent ocular symptom of itching compared to placebo and the difference was statistically significant both at day 7 (p<0.001) and day 14 (p<0.01).
No significant complications of tropical ketorolac were observed during the trial. Transient stinging sensation was observed by three patients (14.3%) in the ketorolac group but it did not lead to any discontinuation of therapy.
In conclusion, topical ketorolac tromethamine 0.5% solution was found safe and appeared effective in treatment of VKC. However, a larger study is required to confirm these results.
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[Figure - 1]
[Table - 1], [Table - 2]