Topical NSAIDs in ocular surgery: A head-to-head trial of Nepafenac versus bromfenac after phacoemulsification

Introduction

Cataract remains a predominant cause of reversible visual impairment globally, particularly in aging populations. Phacoemulsification, owing to its rapid recovery and minimal invasiveness, has become the standard surgical technique for cataract removal [1] . Despite the precision and safety associated with modern cataract extraction, postoperative inflammation continues to be a significant concern, potentially impairing visual rehabilitation and leading to complications such as cystoid macular edema (CME) [2] . This inflammation results primarily from the disruption of the blood-aqueous barrier following intraocular manipulation. It is characterized clinically by anterior chamber cells and flare, which reflect the infiltration of leukocytes and protein exudation [3] . Effective control of this inflammation is crucial to minimize the risk of CME and to enhance postoperative comfort and visual outcomes [4] . Traditionally, topical corticosteroids have been the mainstay of postoperative anti-inflammatory therapy. However, their use is limited by potential side effects including elevated intraocular pressure, delayed wound healing, and increased susceptibility to infections [5] . Topical nonsteroidal anti-inflammatory drugs (NSAIDs) have emerged as a valuable alternative or adjunct to corticosteroids due to their targeted cyclooxygenase (COX) inhibition and lower incidence of steroid-associated complications [6] . Among the various NSAIDs used in ophthalmology, Nepafenac and bromfenac have gained widespread clinical acceptance due to their favorable pharmacokinetic profiles and once-daily dosing convenience [7] . Nepafenac, a prodrug that is hydrolyzed to amfenac within ocular tissues, allows enhanced penetration and site-specific anti-inflammatory activity [8] . Bromfenac, on the other hand, is a potent COX-2 inhibitor with improved lipophilicity, providing sustained anti-inflammatory action [9] . Although both agents are approved for postoperative inflammation control, comparative clinical data remain inconclusive. Some studies have reported that bromfenac may provide superior reduction in macular thickening, whereas others suggest comparable efficacy between the two drugs in reducing inflammation and pain [10] . Moreover, subtle differences in molecular structure, tissue distribution, and onset of action could potentially influence clinical outcomes. This study aims to fill the existing gap in direct comparative evidence by evaluating the clinical efficacy of Nepafenac versus bromfenac in managing postoperative inflammation following phacoemulsification cataract surgery. The study focuses on objective parameters such as anterior chamber cell and flare grades, central macular thickness (CMT), and subjective discomfort levels.

Materials and Methods Study Design and Setting

This was a prospective, randomized, single-blinded, comparative clinical study conducted at the Department of Ophthalmology, Sree Balaji Medical College and Hospital, Chennai, over a period of 12 months (from Janurary 2016 to Decemebr 2016). The study was approved by the Institutional Ethics Committee. Written informed consent was obtained from all participants prior to enrollment.

Study Population

A total of 120 patients scheduled for elective unilateral phacoemulsification cataract surgery with intraocular lens (IOL) implantation were included. Patients were recruited based on the following inclusion criteria: Age 50-80 years, senile cataract with Grade II-III nuclear sclerosis, no history of ocular inflammation or intraocular surgery, and ability to provide informed consent. Exclusion criteria included, preexisting ocular conditions such as glaucoma, uveitis, or diabetic retinopathy, use of systemic or topical antiinflammatory medication within one month prior to surgery, known hypersensitivity to NSAIDs, intraoperative complications (e.g., posterior capsule rupture), and poor media clarity impeding postoperative imaging.

Randomization and Intervention

Patients were randomized into two equal groups (N=60 each) using a computer-generated random number table.  Group A: Received 0.1% Nepafenac ophthalmic suspension, instilled once daily for 28 days postoperatively.  Group B: Received 0.09% bromfenac ophthalmic solution, also instilled once daily for the same duration.

Both medications were initiated 24 hours post-surgery, with all patients receiving standard postoperative care including topical antibiotics and lubricants. No corticosteroids were prescribed to isolate the anti-inflammatory effects of the study drugs.

Outcome Measures

Primary outcomes included anterior chamber inflammation assessed via slit-lamp biomicroscopy using the Standardization of Uveitis Nomenclature (SUN) grading for cells and flare. Secondary outcomes included:  Central macular thickness (CMT) measured by spectraldomain optical coherence tomography (OCT; Zeiss Cirrus HD-OCT)  Subjective ocular discomfort using a 10-point Visual Analog Scale (VAS) Assessments were performed on postoperative days 1, 7, 14, and 28 by a masked examiner.

Statistical Analysis

All data were entered into Microsoft Excel and analyzed using SPSS software. Descriptive statistics were used for demographic variables. Quantitative data were compared using unpaired Student's t-test, while categorical variables were analyzed using chi-square test. A p-value < 0.05 was considered statistically significant. Confidence intervals (95% CI) were calculated for key comparisons. Sample size was calculated to detect a minimum 15% difference in inflammation scores with 80% power and α = 0.05.

Results

Table Central macular thickness (CMT), a critical marker for macular edema, was lower in the bromfenac group throughout the postoperative period. On day 28, mean CMT was 204.9 µm in the bromfenac group compared to 212.7 µm in the Nepafenac group (P=0.008), suggesting better macular protection and lower risk of edema with bromfenac. Subjective discomfort measured via the visual analog scale (VAS) showed significantly reduced scores in the bromfenac group from day 7 onward (2.5±0.8 vs. 3.1±1.0, P=0.014), with this trend persisting through day 28 (0.5±0.3 vs. 0.8±0.5, P=0.032), indicating better tolerability and symptom relief.

Discussion

Phacoemulsification, while minimally invasive, triggers postoperative inflammation due to disruption the bloodaqueous barrier, leading to prostaglandin-mediated responses [11] . If unaddressed, this inflammation may result in cystoid macular edema (CME) and suboptimal visual recovery [12] . While corticosteroids have traditionally served as first-line therapy, topical nonsteroidal anti-inflammatory drugs (NSAIDs) are increasingly favored due to their more favorable side effect profile and targeted cyclooxygenase (COX) inhibition [13] .

In the present study, bromfenac demonstrated significantly greater efficacy than Nepafenac in reducing anterior chamber cell grades, central macular thickness (CMT), and patient-reported discomfort scores over a four-week postoperative period. These findings are consistent with the pharmacological profile of bromfenac, which possesses enhanced COX-2 selectivity and superior ocular bioavailability, as reported by Yanni et al. [14] . Walters and Goldberg [15] , in a comparative trial, found that bromfenac reduced CME incidence more effectively than Nepafenac, particularly in diabetic patients a trend echoed in our findings, where macular thickness was consistently lower in the bromfenac group. Similarly, Yilmaz et al. [16] reported that bromfenac provided faster resolution of anterior chamber inflammation and improved ocular comfort when compared to Nepafenac. Our data corroborate this, with statistically significant differences emerging from postoperative day 7 onward. Nepafenac, as a prodrug converted into amfenac, is known for its ability to penetrate posterior ocular tissues. However, studies such as those by Gamache et al. [17] have noted that bromfenac's higher lipophilicity and tissue-binding capacity result in more sustained intraocular anti-inflammatory effects. These attributes likely explain the greater reduction in CMT observed in the bromfenac group in our study (204.9 µm vs 212.7 µm at day 28, P=0.008). Donnenfeld et al. [18] emphasized the importance of simplified once-daily regimens for elderly patients, especially given the prevalence of polypharmacy. In our study, the better VAS scores in the bromfenac group support this, suggesting higher patient adherence and comfort.

Conclusion

This study demonstrated that both Nepafenac and bromfenac are effective in managing postoperative inflammation following phacoemulsification. However, bromfenac showed superior efficacy in reducing anterior chamber inflammation, maintaining lower central macular thickness, and enhancing subjective patient comfort throughout the recovery period. The statistically significant improvements observed with bromfenac suggest that it may offer better prophylaxis against cystoid macular edema and provide greater symptom relief with a comparable safety profile. Given its once-daily dosing and higher patient tolerability, bromfenac appears to be a more suitable option for routine anti-inflammatory therapy after cataract surgery. Further multicenter trials with longer follow-up durations may strengthen the clinical consensus regarding its superiority in varied patient populations.

Acknowledgement

AcknowledgementThe authors would like to thank the institutional staff for their support during the conduct of this study.

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