Ocular allergy is a commonly encountered pathology in clinical practice, with an increase in number of patients noticed in the last decade.[1 2 3 4 5 6 7 8 9 10 11
Avoidance of allergans and lubricants plays a key role in the management of allergic conjunctivitis. Addition of anti-histaminics such as levocarbastine reduce inflammation, whereas mast cell stabilizers prevent mast cell degranulation on exposure to allergans.[12 13 14 15 16 olopatadine , bepotastine, and alcaftadine) are FDA approved for use in allergic conjunctivitis, but there is not much literature comparing these three agents directly. There are a few masked trials available, but this study is a double-blinded, observer-masked trial directly comparing the efficacy of three topical anti-allergic medications in mild to moderate allergic conjunctivitis.
Methods
This was a prospective, observer-masked, single center clinical trial conducted at a tertiary care center in South India. The protocol was registered with the Ethics Committee of our Institute and adhered to the tenets of the Declaration of Helsinki. Consecutive 45 patients with mild to moderate allergic conjunctivitis [Table 1 ] presenting to outpatient department and willing to participate in the study were included after written informed consent. The criteria for exclusion were need for topical steroids or topical immunosuppressives, contact lens wearers, concurrent ocular diseases such as dry eye, planning to undergo ocular surgery during study period, known hypersensitivity to either agent, a history of alcohol or drug abuse, a positive history of an ocular herpetic infection, an active ocular infection, or any significant illness, actively taking systemic steroids or antihistamines within 7 days prior to enrolment, pregnant, planning to become pregnant, or nursing/lactating and use of any other topical ocular medications.
Table 1: Classification of allergic conjunctivitis
Patients were sequentially enrolled in one of the three groups according to computer-generated random numbers and given topical anti-allergic medication for twice daily use.
Group 1: Topical 0.1% Olopatadine eyedrops BID
Group 2: Topical 1.5% Bepotastine eyedrops BID
Group 3: Topical 0.25% Alcafatadine eyedrops BID
All patients received lubricants and were asked to use and note down whenever they needed these eyedrops. Patients were instructed to use gentle eyelid closure for at least 2 min after dosing, and to repeat instillation of a single drop, if there was uncertainty as to whether successful instillation of the treatment had occurred.
For uniform grading of symptoms and signs at each visit, we used scoring scales with 0 indicating no itch and 3 indicating constant desire to itch. Ocular redness and discharge were scored using 5-point scale (0–4), where 0 indicated no redness or no discharge and 4 indicated severe redness or copious discharge. Foreign body sensation and watering were graded using the 4-point scale (0–3), where 0 indicated absent symptoms and 3 indicated severe foreign body sensation or constant epiphora. In signs, upper tarsal papillae were graded using 4-point scale (0–3) with 0 indicating no papillae and 3 indicating predominance of giant papillae. Similarly, limbal activity was graded using 4-point scale with 0 indicating no limbal activity and 3 indicating Horner Tranta dots.[17
Before starting treatment, patients filled a questionnaire grading their symptoms, and the signs were evaluated by a masked investigator [Table 2 ]. The instillation of the first eyedrop of anti-allergic medication was done in the outpatient department, and the patient was asked to fill the same questionnaire after 15 min and telephonically on the next day. Patients were reviewed at 1 week and 1 month. Masked investigator assessed signs, and patient completed the questionnaire form at review visits.
Table 2: Proforma used for recording symptoms and signs of patients at each visit
The sample size was calculated to detect a difference in means of 0.70 units assuming that the common standard deviation is 1.00.[18 P values were two-tailed at a significance level of 0.05. Intention to treat analysis was done in this trial.
Results
We did not have any study drop out as all the patients came for follow-up visits. Age and gender distribution of patients in three groups is shown in Table 3 . Number of patients with moderate allergic conjunctivitis in three groups were group 1: 6/15 (40%); group 2: 5/15 (33.3%); and group 3: 4/15 (26.6%). Mean time for the beginning of relief of itching was comparable in three groups with no statistically significant difference (P > 0.05, range 5-15 min, mean: group 1- 8.67, group 2-8.33, group 3-8.33 min). All three medications showed statistically significant relief in itching, with effect starting in minutes and complete relief of itching at 1-week follow-up. [Shown in Table 4 and Figure 1 ] After 15 min of instillation of eyedrop, patients in all three groups had either no or minimal itching (itch score of 0 or 1), illustrating quick onset of action of all three medications. All three medications helped in relief of other symptoms such as redness, watering, discharge, and foreign body sensation with complete symptomatic relief in 1 week time [Figure 2 ]. None of the patients needed topical steroid for worsening symptoms. All three medications were well-tolerated except for mild burning sensation noticed by a few patients, which was transient in nature. Such symptoms were noted by 2 patients (13%) in group 1, 4 patients (26%) in group 2, and 6 patients (40%) in group 3.
Table 3: Age and gender distribution of patients in each group
Table 4: Paired analysis of mean itch scores at various time intervals (in three groups)
Figure 1: Bar graphs showing distribution of itch score of patients in three groups at various time intervals
Figure 2: Bar diagrams showing number of patients with relief of symptoms at various time points. Relief is considered as absence of symptom or two-point reduction from the level at presentation
As we included cases with only mild to moderate allergic conjunctivitis, severe upper tarsal papillae or Horner Tranta dots were not noted in the study group. Patients included in the study had ocular signs such as few upper tarsal papillae and limbal hyperemia, which did not respond to these topical medications.
Discussion
Most of the earlier studies comparing the efficacy of anti-allergic medications were according to conjunctival allergan challenge.[18 19 20 21 22 23
Alcaftadine 0.25%, olopatadine 0.2%, and bepotastine 1.5% eyedrops have been proved to be safe and well-tolerated topical medication for allergic conjunctivitis.[18 19 21 22 23
Efficacy of these anti-allergic medications over placebo has been proved in previous studies.[18 19 21 22 23
Comparative trials done earlier have not compared these three medications in a single randomized control trial. Among 0.25% alcaftadine and 0.2% olopatadine in a study using conjunctival allergan challenge, alcaftadine was found superior to olopatadine at the earliest time point (3 min post-challenge). Only alcaftadine provided significant relief in chemosis at 16 and 24 h post-instillation.[18 olopatadine was noted in another study enrolling 284 subjects. They found that subjects treated with alcaftadine had a lower overall mean itch score at 3, 5, and 7 min than the subjects treated with olopatadine .[19 22 olopatadine and alcaftadine showed similar efficacy profiles and mast cell numbers. Alcaftadine prevented a decrease in expression of the junctional protein, ZO-1, which is caused by allergan challenge. In addition, animals treated with alcaftadine showed significantly lower conjunctival eosinophil infiltration.[24 olopatadine and bepotastine showed better relief of ocular allergy symptoms and relief of runny nose. They found that a higher percentage of patients preferred bepotastine over olopatadine for treatment.[20
An additional part of our study was an independent masked observer for evaluation of signs of allergic conjunctivitis. We found that these medications did not help in regression of signs such as limbal or palpebral papillae. This hints toward the benefit of these medications for symptomatic relief alone in cases of allergic conjunctivitis. More potent anti-allergic medications like topical steroids should be considered in cases with significant palpebral and limbal papillae.
Although our sample size is small, we conducted a thorough observer-masked evaluation of each case at regular intervals for 1 month.
Conclusion
We concluded a similar efficacy of three medications in relieving symptoms and inefficacy in regressing signs in cases of allergic conjunctivitis.
Patient consent
Written informed consent was taken from every patient included in the study.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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