Corneal Thickness and Anterior Chamber Flare After Cataract Surgery: A Randomized Controlled Trial Comparing Five Regimens for Anti-Inflammatory Prophylaxis

Abstract

Purpose

To investigate the relationship between early post-operative anterior chamber inflammation (aqueous flare) and central corneal thickness (CCT) after cataract surgery and to evaluate the effect of anti-inflammatory prophylaxis on CCT.

Setting

Department of Ophthalmology, Rigshospitalet-Glostrup, University Hospital Copenhagen, Denmark.

Design

Post-hoc analysis of a prospective randomized controlled trial.

Patients and Methods

A total of 470 participants who underwent standard cataract surgery were randomly allocated to prophylactic treatment with nonsteroidal anti-inflammatory drug (NSAID, groups C and D) or a combination of NSAID and steroid eye drops (groups A and B), commenced either pre-operatively (A and C) or post-operatively on the day of surgery (B and D), or “drop-less surgery” (peri-operative subtenon depot of dexamethasone, group E). Aqueous flare was measured before and three days after surgery. CCT was measured before surgery, three days, three weeks, and three months after surgery. Data were analyzed according to the intention-to-treat method.

Results

Doubling of aqueous flare increased mean CCT by 15.6 microns (95% CI 9.8; 21.3, P<0.001) three days after surgery. Mean CCT increased from 549 microns (95% CI 545; 552) at baseline to 594 microns (95% CI 585; 602) three days after surgery and returned to 551 microns (95% CI 545; 557) three months after surgery. Mean CCT was thinner in group C compared to group A three days after surgery. No difference was found for any other groups or time points.

Conclusion

Increased anterior chamber inflammation was associated with significant corneal thickening three days after cataract surgery. Choice of anti-inflammatory regimen seemed to be of no or minimal importance on CCT when the effect of inflammation was accounted for. Corneal thickening is possibly mediated by underlying deterioration of the blood-aqueous barrier and corneal endothelium pump function caused by a post-operative inflammatory response.

Keywords:

• cataract surgery
• anterior chamber inflammation
• central corneal thickness
• NSAID

Abbreviations

ACD, anterior chamber depth; AMD, age-related macular degeneration; AREDS, age-related eye disease study; BAB, blood-aqueous barrier; CCT, central corneal thickness; CDE, cumulated dissipated energy; CDVA, corrected distance visual acuity; CI, confidence interval; drop-less surgery, surgery where a peri-operatively placed subtenon depot of dexamethasone acted as post-operative anti-inflammatory treatment; ETDRS, Early Treatment Diabetic Retinopathy Study; EudraCT, European Union Drug Regulating Authorities Clinical Trials; FDA, United States Food and Drug Administration; FDR, False Discovery Rate; FLACS, Femtosecond laser-assisted cataract surgery; GCP, good clinical practice; Group A, intervention group that received Prednisolone + NSAID eye drop combination therapy initiated three days before surgery; Group B, intervention group that received Prednisolone + NSAID eye drop combination therapy initiated post-operatively on the day of surgery; Group C, intervention group that received NSAID eye drop mono therapy initiated three days before surgery; Group D, intervention group that received NSAID eye drop mono therapy initiated post-operatively on the day of surgery; Group E, intervention group that received therapy with a peri-operative subtenon depot of dexamethasone (drop-less surgery); IOL, intra-ocular lens; IOP, intra-ocular pressure; LogMAR, Logarithm to the Minimal Angle of Resolution; NSAID, nonsteroidal anti-inflammatory drug; OCT, optical coherence tomography.

Data Sharing Statement

The datasets generated and analyzed during the current study are not publicly available to avoid compromising patient confidentiality. Data are available from the corresponding author on reasonable request.

Ethics Approval and Informed Consent

The study was approved by the Danish Medicines Agency (Journal nr.: 2017064331), the Committee on Health Research Ethics, Capital Region, Denmark (Journal nr.: H-17025182) and The Danish Data Protection Agency (RH-2017-291, I-Suite nr.: 05860) and was monitored according to the good clinical practice (GCP) quality standard by the GCP unit at Copenhagen University Hospital. The study was conducted in accordance with the Declaration of Helsinki and all study participants provided written informed consent.

Author Contributions

JHE was responsible for data collection. NCH and JHE performed the statistical analysis. JHE, LMH and LK secured funding. All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

The study received funding from the Independent Research Fund Denmark (DFF – 7016-00161), Fight for Sight - Denmark and Henry og Astrid Møllers Fond. Funding bodies had no role in the study design, collection of data, data analysis, decision to publish, or preparation of the manuscript.