Prednisolone and Ketorolac vs Ketorolac Monotherapy or Sub-Tenon Prophylaxis for Macular Thickening in Cataract Surgery: A Randomized Clinical Trial

Abstract

Importance: The choice of anti-inflammatory prophylaxis parallel to cataract surgery is important for patient safety and successful outcome of surgery, but which regimen to choose is contested.

Objectives: To determine whether a combination of prednisolone and nonsteroidal anti-inflammatory drug (NSAID) eye drops was superior in preventing increased central macular thickness (central subfield thickness [CST]) after uncomplicated cataract surgery compared with NSAID monotherapy and sub-Tenon capsule depot (dropless surgery), and to test whether preoperative initiation of eye drop treatment was superior to initiation on the day of surgery.

Design, setting, and participants: This investigator-driven, single-center, randomized clinical trial with masked statistical analyses enrolled patients at the Department of Ophthalmology, Rigshospitalet Glostrup, Glostrup, Denmark, from February 1, 2018, to August 15, 2019. Follow-up was completed December 18, 2019. Participants included low-risk patients undergoing phacoemulsification for age-related cataract by an experienced surgeon (1 eye per participant). Data were analyzed from February 17 to June 15, 2020.

Interventions: Participants scheduled for cataract removal were randomized to 1 of 5 anti-inflammatory prophylactic regimens: eye drops with a combination of prednisolone, 1%, and ketorolac tromethamine, 0.5%, with or without preoperative initiation (preoperative prednisolone plus NSAID [control] and postoperative prednisolone plus NSAID groups), ketorolac monotherapy with or without preoperative initiation (preoperative and postoperative NSAID groups), or sub-Tenon depot of dexamethasone phosphate (sub-Tenon group). Eye drops were administered 3 times per day until 3 weeks postoperatively.

Main outcomes and measures: CST 3 months postoperatively.

Results: A total of 470 participants (mean [SD] age, 72.2 [7.0] years; 290 women [61.7%]) with 94 participants in each group were included in the analysis. Three months after surgery, the mean CST was 250.7 (95% CI, 247.6-253.7) μm in the preoperative prednisolone plus NSAID group, 250.7 (95% CI, 247.8-253.7) μm in the postoperative prednisolone plus NSAID group, 251.3 (95% CI, 248.2-254.4) μm in the preoperative NSAID group, 249.2 (95% CI, 246.2-252.3) μm in the postoperative NSAID group, and 255.2 (95% CI, 252.0-258.3) μm in the sub-Tenon group. There were no significant differences in CST or visual acuity compared with control and no differences between preoperative and postoperative groups, but 47 of 83 participants (56.6%) in the sub-Tenon group needed additional anti-inflammatory treatment.

Conclusions and relevance: No differences in CST or visual acuity were detected between the combination of prednisolone and NSAID eye drops vs NSAID monotherapy or sub-Tenon dexamethasone depot, although more than one-half of patients in the sub-Tenon arm received additional anti-inflammatory treatment. Initiating prophylaxis 3 days preoperatively was not superior to initiation on the day of surgery. Monotherapy with NSAIDs may be preferred in uncomplicated cataract surgery.

Trial registration: ClinicalTrials.gov Identifier: NCT03383328.

Figure 1.. Consort Diagram for Flow of Participants

Preoperative prednisolone plus nonsteroidal anti-inflammatory drug (NSAID) indicates group receiving a combination of prednisolone, 1%, and ketorolac tromethamine, 0.5%, eye drops 3 times per day until 3 weeks after surgery with initiation 3 days before surgery; postoperative prednisolone plus NSAID, group receiving a combination of prednisolone, 1%, and ketorolac, 0.5%, eye drops 3 times per day until 3 weeks after surgery with initiation on the day of surgery; preoperative NSAID, group receiving monotherapy with ketorolac, 0.5%, eye drops 3 times per day until 3 weeks after surgery with initiation 3 days before surgery; postoperative NSAID, group receiving monotherapy with ketorolac, 0.5%, eye drops 3 times per day until 3 weeks after surgery with initiation on the day of surgery; and sub-Tenon, group receiving sub-Tenon depot consisting of 0.5 mL of dexamethasone phosphate, 4 mg/mL. Participants who withdrew did so before surgery and before investigational medicine was administered; for those outside the time frame, postoperative visits took place outside the prespecified 2 to 4 days for the 3-day visit, 14 to 28 days for the 3-week visit, and 60 to 120 days for the 3-month visit. Some participants who attended a visit outside the specified time frame returned for the next postoperative visit within the specified time frame of that visit.

Figure 2.. Mean Central Subfield Thickness (CST) From Baseline to 3 Months After Surgery

Error bars represent 95% CIs. Only 1 error bar is presented at baseline because estimates per definition are the same for all groups in the constrained linear mixed model with inherent baseline adjustment. Groups are described in the legend for Figure 1.