Although the non-steroidal anti-inflammatory drugs (NSAIDs) have almost replaced steroids in providing an effective anti-inflammatory alternative after cataract surgery,1234 this is not so following strabismus surgery. In a 1997 survey of strabismologists more than 90% respondents were using topical corticosteroids after surgery.5 Since steroids are associated with risks of delayed wound healing,6 decreased resistance to infections and intraocular pressure (IOP) elevations,78 it is prudent to replace them with a safer alternative. Only recently have NSAIDs been considered equally effective in controlling postoperative pain and inflammation in strabismus surgery.9101112
We designed a prospective, randomized, double-blind, single-center, clinical trial to compare the anti-inflammatory action of topical diclofenac sodium (0.1% ophthalmic solution) with topical dexamethasone (0.1% ophthalmic solution) after strabismus surgery. The main outcome measure was the evaluation of the inflammatory response and the secondary outcome was the IOP during follow-up.
Materials and Methods
After approval from the faculty ethical committee and obtaining an informed consent, 48 consecutive patients, referred to the strabismus clinic were included. The cases were recruited if they had constant strabismus and needed uniocular recession-resection surgery on two horizontal rectus muscles. They were not enrolled if any of the following criteria were present: (1) a history of strabismus surgery, (2) underwent > two muscle surgery or bilateral surgery, (3) too young to cooperate with IOP assessment or to provide an adequate response to our pre-tested questionnaire, (4) a known hypersensitivity to the drugs used in the study, (5) neurological anomaly or systemic disorder, (6) ocular inflammatory condition, whether active or healed or (7) use of systemic anti-inflammatory drugs in the last four weeks.
Baseline parameters were recorded. All cases were operated in a similar manner by a single surgeon (AKA). Ciprofloxacin 0.3% four times daily was instilled into the eye starting a day prior to surgery and was continued postoperatively for four weeks. Children were operated under inhalational halothane and the adults under standard peribulbar anesthesia. The horizontal rectus muscles were approached via Von Noorden's limbal conjunctival incisions, 6mm long and concentric with the limbus, extended by two radial cuts posteriorly 5mm in length. No cautery was used. Muscle-scleral attachments were made with 6/0 Vicryl (Ethicon; NW 2670), while the conjunctival closure was obtained by 8/0 Vicryl (Ethicon; NW 2348), using buried knots with four sutures. Block randomization (in blocks of six) was done to allocate the cases to receive either dexamethasone sodium 0.1% (NSAID: Syntho Pharmaceuticals Pvt. Ltd., Lucknow) or diclofenac sodium 0.1% eye drops (Solodex: Jawa Pharmaceutical Pvt. Ltd., Gurgaon), in identical vials. The nature of the drug was masked from the patients, the surgeon and the assessor by removing the labels from similar 5ml bottles and sealing three such bottles in one opaque sachet. Patients were given identical instructions to instill the study drops four times a day for four weeks. The unmasking was done at the time of the final analyses after the data collection was completed.
The patients were evaluated on the first postoperative day and at two and four weeks after surgery. The conjunctival injection over the site of muscle attachments was graded objectively by comparing against a series of color photographs. Inflammatory symptoms were analyzed subjectively by a questionnaire assessing patient discomfort, discharge and drop intolerance. Chemosis was graded as absent to severe. Inflammatory parameters were scored as: 0 (nil), 1 (mild), 2 (moderate) or a 3 (severe) response. Additionally, we algebraically added the grading of the five inflammatory characteristics to arrive at a total inflammatory score (TIS): possible range 0 (minimum) to 15 (maximum). The IOP was recorded by Goldmann applanation tonometer. For each subject, at each follow-up, we calculated the difference in IOP from baseline, to evaluate the net change in IOP. Any patients not available at two-week or four-week follow-up, were considered as lost to follow-up and excluded from the analyses.
Since the main outcome variables were graded responses, to be analyzed by the non-parametric test, we considered that a minimum of 20 patients in each group would suffice for the study. Statistical analyses were performed using SPSS for Window, Version 10. Bivariate data were analyzed by chi square statistic, while continuous (parametric) and graded variables (non-parametric) were subjected to t-test and the Mann Whitney U test respectively. Significance was set at P ≤ 0.05.
Of the 87 patients initially assessed for the study, five refused consent and 34 did not meet the inclusion criteria [Fig. 1]. The remaining 48 patients were randomized (24 in each group). Five were lost to follow-up. We thus finally analyzed 43 cases: 21 in the dexamethasone group and 22 in the diclofenac group. The groups were comparable in their baseline characteristics, including preoperative IOP [Table 1]. The subjects were analyzed on intention to treat basis.
The two groups were comparable in age, gender, preoperative IOP, amount and type of strabismus, proportion with onset prior to five years-age and proportion undergoing strabismus surgery under general anesthesia [Table 1]. Surgery was uncomplicated in all cases.
Table 2 depicts the graded response to each of the five inflammatory variables under study at follow-up. No significant differences were observed on the Mann-Whitney U test (P > 0.05). The TIS was comparable throughout the follow-up [Table 3]. On the first postoperative day, there was no significant difference in the IOP between the two groups (P = 0.36) [Table 3]. The mean IOP in the dexamethasone group was significantly higher at two weeks (P = 0.03, 95% CI for difference 0.17 to 3.25) and at four weeks (P = 0.002, 95% CI for difference 1.09 to 4.24) compared to the diclofenac group. The net rise of IOP from baseline was statistically significant only at four weeks (µ rise: 1.07, 95% CI 0.60 to 3.14).
Similar to our result, no statistical difference in discomfort level has been reported by others.91011 Although Apt et al.12 arrived at a similar conclusion, they used oral analgesics in both the groups. Snir10 reported a significantly lesser discomfort (and pain) at two weeks (P = 0.003) and at four weeks (P = 0.02) with diclofenac.
Akin to us, previous studies have1112 failed to detect any significant difference for chemosis and injection. In contrast Snir et al.10 found significantly less chemosis (P = 0.02) and inflammation (P = 0.04) in the diclofenac group at two weeks, but this did not persist until the fourth week postoperatively. Apt et al.12 evaluated discharge between the two groups, although only until one week postoperatively. Like us, they found no significant dissimilarity between the two groups.
We could not find any study which explicitly discussed drop intolerance. Wright et al.9 may have referred to it where they report that both the treatments were well tolerated with parents reporting either no or only mild discomfort after instillation of eye drops with no difference between groups. Unfortunately, this is a subjective variable and imprecisely recorded, especially in cases of children. Our study, it may be argued would score marginally better because the older age group may yield a clearer response to such a query. We failed to detect any significant difference between the two groups for drop intolerance. It is important to point out that the preservatives were different in the two groups: diclofenac having benzalkonium chloride 0.02% and dexamethasone having phenyl mercuric nitrite 0.001%. There thus remains a possibility that despite their small quantities, they may influence and confound this outcome.
Wright et al.9 used total inflammatory scores to compare betamethasone-neomycin and diclofenac-gentamycin groups. Similarly, we used a standard series of clinical photographs to grade and compare injection over the site of muscle surgery thereby increasing objectivity in the assessment. We failed to demonstrate any significant difference in the TIS between the two groups at any point during four weeks of follow-up.
Similar to our results, other authors1011 have demonstrated statistically significant ocular hypertensive response to dexamethasone compared to diclofenac after strabismus surgery. The ocular hypertensive response may be greater in children on account of the immaturity of the trabecular meshwork.13 This implies that an immature trabecular meshwork may have a greater predisposition to a hypertensive response to steroids. Since more than 88% of our cases were older than 10 years and thus have a more mature trabecular meshwork compared to children, this could explain the lack of any clinically meaningful ocular hypertensive response in the present study.
We lacked a 'no treatment arm', the importance of which is brought out by Wortham et al.14 when they demonstrated that the anti-inflammatory response to prednisolone 1% was equivalent to a placebo (polyvinyl alcohol 0.4%). Unfortunately our study did not include a further follow-up to identify the time period when the IOP in the two groups became equivalent.
It is concluded that instillation of diclofenac 0.1% drops after strabismus surgery is comparable to dexamethasone 0.1% in providing anti-inflammatory and analgesic effect and has the advantage of significantly lesser rise of intraocular pressure.
Source of Support:
Conflict of Interest:
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