Comparison of topical nepafenac 0.1% and 0.3% on aqueous flare and macular thickness in patients with pseudoexfoliation following cataract surgery

Abstract

Purpose:

To evaluate and compare the efficacy of topical nepafenac 0.1% administered three times daily versus nepafenac 0.3% administered once daily in patients with pseudoexfoliation syndrome (PEX) following routine cataract surgery.

Methods:

In this retrospective cohort study, patients with PEX undergoing routine cataract surgery were divided into two groups for analysis. Group 1 received nepafenac 0.1% three times daily, while Group 2 received nepafenac 0.3% once daily. In both groups, nepafenac was started 1 day before surgery and continued for 2 weeks postoperatively. Anterior chamber flare was quantified using laser flare photometry (LFP), and central macular thickness (CMT) was measured using optical coherence tomography. Measurements were taken preoperatively, at 1 week, and at 6 weeks postoperatively.

Results:

The study included 85 eyes from 85 patients, with 39 eyes in Group 1 and 46 eyes in Group 2. During the first postoperative week, Group 2 showed a significant reduction in LFP measurements (P = 0.047) compared to Group 1. Notably, no significant difference was observed between the groups at the preoperative visit or at postoperative week 6. Comparisons of preoperative, 1-week, and 6-week postoperative CMT values also revealed no significant differences between the groups.

Conclusion:

Nepafenac 0.3% used in routine cataract surgery in patients with PEX was shown to be at least as effective as nepafenac 0.1% in terms of aqueous flare and CMT. Aqueous flare values were more favorable with nepafenac 0.3% during the first week. In addition, the convenience of once-daily dosing may offer further advantages.

Pseudoexfoliation syndrome (PEX) constitutes a prevalent condition associated with advanced age, and it is distinguished by the anomalous formation and deposition of fibrillar extracellular material in a multitude of tissues, including eyes.[1] The ocular manifestations involve nearly all components of the anterior eye, including the cornea, iris, iridocorneal angle, lens, and zonular fibers.[2,3]

Previous research has indicated that alterations in the blood–aqueous barrier (BAB) are present in eyes with PEX.[4,5,6,7,8] As a consequence, the degree of postoperative inflammation is greater in PEX cataracts than in routine cataracts.[2,9,10] It can be proposed that the fragility of BAB and the prominent postoperative inflammatory response observed in some cases may contribute to an elevated risk of developing cystoid macular edema in eyes with PEX.[11,12,13]

Conventionally, ocular inflammation assessment is based on a subjective examination of the anterior chamber at the slit lamp, a method that is semi-quantitative and exhibits low reproducibility.[14,15] Laser flare photometry (LFP) is an effective, noninvasive, and highly reproducible quantitative method to evaluate variations in anterior chamber aqueous flare, which may prove useful in assessing patients diagnosed with PEX.[16]

Nepafenac 0.1% is a nonsteroidal anti-inflammatory drug (NSAID) used to treat intraocular inflammation following phacoemulsification.[17] As a prodrug, nepafenac quickly penetrates the cornea and is converted into its active form, amfenac, by intraocular enzymes. This conversion takes place in vascular tissues such as the retina, choroid, ciliary body, and iris.[18,19] Nepafenac is considered more effective than other topical NSAIDs due to its superior corneal penetration, targeted tissue activation, longer action duration, and extended inhibition of prostaglandin release.[20,21] The 0.3% nepafenac formulation, which has received US Food and Drug Administration approval, features a higher concentration of the active metabolite, reduced particle size for better absorption, and a guar-based retentive system that enhances its bioavailability, compared to the 0.1% version.[22]

In this study, we aimed to compare the effects of topical nepafenac 0.1% administered three times daily versus 0.3% administered once daily in patients with PEX following cataract surgery using optical coherence tomography (OCT) for central macular parameters and LFP.

Methods

This retrospective study was performed at a tertiary eye care hospital with the approval of the local ethics committee and institutional review board. All participants in the study provided written informed consent in compliance with the ethical principles outlined in the Helsinki Declaration.

Patients with PEX and older than 50 years of age with senile cataract who underwent routine phacoemulsification with intraocular lens (IOL) implantation in the bag between January 2024 and July 2024 were included in the study. Exclusion criteria were any history of previous intraocular surgery or trauma, any complication during the surgery (capsular tear, vitreous loss, zonular dialysis, floppy iris syndrome, etc.), ocular diseases other than senile cataract (glaucoma, uveitis, corneal and retinal pathologies, etc.), systemic diseases like diabetes mellitus and uncontrolled hypertension, connective tissue disorders, history of allergy to nepafenac, and patients who used steroids, NSAIDs, or prostaglandins in the previous month.

Participants were divided into two groups: nepafenac 0.1% (Apfecto 0.1%; World Medicine Ophthalmics, Essex, UK) three times daily (Group 1) and nepafenac 0.3% (Apfecto 0.3%; World Medicine Ophthalmics, Essex, UK) once daily (Group 2). The type of eyedrop was selected at the discretion of the clinician. All patients received nepafenac for 1 day preoperatively and 2 weeks postoperatively. In addition, all eyes received topical moxifloxacin 0.5% four times a day for a week after surgery and prednisolone acetate 1% eye drops starting four times a day and tapering in 4 weeks. One skilled surgeon conducted all procedures under topical anesthesia using a standard 2.4-mm clear corneal incision, phacoemulsification through the Centurion system (Alcon, Fort Worth, TX, USA), ophthalmic viscosurgical device (Duovisc; Alcon, Fort Worth, TX, USA), and a hydrophilic acrylic IOL placed within the bag. At the end of the surgical procedure, intracameral cefuroxime was administered.

All patients underwent a thorough ophthalmological assessment, which included taking the best-corrected visual acuity (BCVA), examining the anterior segment using a slit lamp, measuring intraocular pressure (IOP), and dilated fundus examinations both before and following the surgery. All the patients underwent postoperative examination on day 1, week 1, and week 6.

LFP was conducted using the Kowa FM 700 laser flare meter (Kowa Company Ltd, Nagoya, Japan). The measurements were obtained by a single skilled technician and were conducted in accordance with the manufacturer’s instructions. Central macular thickness (CMT) measurements were performed using Xephilio OCT-S1 (Canon, Tokyo, Japan). The thickness of the central subfield (1.0 mm) and the total macular volume (MV) were recorded.

The statistical analysis was conducted using Statistical Package for the Social Sciences for Windows (version 22.0, SPSS, Inc.). Mean and standard deviation were used to express continuous variables. The Shapiro–Wilk test was used to assess the normality of the data. Student’s t-test was conducted to compare groups when the data had a normal distribution. In the case of data without a normal distribution, Mann–Whitney U test was performed. A P value of <0.05 was considered statistically significant.

Results

The study included 85 eyes from 85 patients. In Group 1, there were 39 patients, with 20 (51.3%) being females. Group 2 consisted of 46 patients, 19 (41.3%) of whom were females. The average age for patients in Group 1 was 73.3 ± 7.8 years, whereas for Group 2 it was 72.1 ± 6.3 years (P = 0.526). There were no significant differences between the two groups regarding baseline IOP, BCVA, central corneal thickness, anterior chamber depth, axial length, mean keratometry, and endothelial cell count (P > 0.05 for all) [Table 1]. In addition, the mean BCVA at the 6-week postoperative follow-up did not show a significant difference between Group 1 (0.90 ± 0.08) and Group 2 (0.87 ± 0.10) (P = 0.367).

Table 1.

Demographics and preoperative measurements of both groups

		Group 1 (n=39)		Group 2 (n=46)		P
Age (years)		73.3±7.8		72.1±6.3		0.526
Gender (F, %)		20 (51.3%)		19 (41.3%)		0.389
IOP (mmHg)		15.4±3.1		16.1±2.8		0.326
BCVA (decimals)		0.2±0.17		0.19±0.14		0.591
AL (mm)		23.01±0.83		23.29±0.82		0.151
ACD (mm)		2.76±0.42		2.80±0.50		0.724
CCT (mm)		520±36		531±37		0.140
K mean (D)		43.26±0.87		44.08±0.63		0.261
ECD (cell/mm2)		2337±340		2284±403		0.210

ACD=anterior chamber depth, AL=axial length, BCVA=best-corrected visual acuity, CCT=central corneal thickness, ECD=endothelial cell density, F=female, IOP=intraocular pressure, K=keratometry

Table 2 shows the phacoemulsification parameters. The mean surgery time was 16.2 ± 5.2 min for Group 1 and 15.8 ± 4.3 min for Group 2 (P = 0.875). No statistically significant differences were observed in the phacoemulsification parameters between the two groups (P > 0.05 for all).

Table 2.

Peroperative measurements of the phacoemulsification parameters

		Group 1 (n=39)		Group 2 (n=46)		P
Surgery time (min)		16.2±5.2		15.8±4.3		0.875
CDE		11.6±4.2		12.3±4.8		0.261
Ultrasound time (sec)		67.5±29.9		73.8±32.3		0.074
Aspiration time (sec)		283.7±89.1		261.2±101.0		0.126
Estimated fluid aspirated (mL)		124.2±39.7		131.4±44.1		0.243

CDE=cumulative dissipated energy

No significant differences in CMT were found between the groups at baseline, 1 week postoperatively, or 6 weeks postoperatively (P > 0.05 for all) [Table 3]. The average increase in CMT from preoperative values to 6 weeks postoperative values was 16.4 ± 10.7 μm in Group 1 and 11.2 ± 8.3 μm in Group 2 (P = 0.074). Within-group analysis of CMT changes revealed a significant difference in Group 1, showing a notable change from its preoperative measurements at 6 weeks postoperatively (P = 0.023). However, no significant differences were observed in other within-group comparisons (P > 0.05 for all) across baseline, 1-week, and 6-week assessments. In addition, there were no significant differences between groups regarding MV at baseline and postoperatively (P > 0.05 for all) [Table 3]. While Group 2 did not show any intraretinal cysts on OCT scans, one patient (2.6%) in Group 1 developed intraretinal cysts by the 6-week mark (P = 0.459).

Table 3.

Measurements of the CMT, MV, and aqueous flare parameters

		Group 1 (n=39)		Group 2 (n=46)		P
CMT (μm)
Baseline     Postoperative week 1     Postoperative week 6		265±45 269±38 281±34		263±42 271±44 274±45		0.707 0.706 0.673
MV (mm3)
Baseline     Postoperative week 1     Postoperative week 6		8.0±0.9 8.2±0.5 8.0±0.7		8.3±1.0 8.4±0.9 8.4±1.0		0.126 0.489 0.213
Flare (ph/ms)
Baseline     Postoperative week 1     Postoperative week 6		15.89±4.98 24.16±6.51 19.63±5.38		16.27±5.41 21.13±5.23 19.05±4.67		0.324 0.047 0.264

CMT=central macular thickness, MV=macular volume, The bold value indicates a P < 0.05.

Comparison of the mean LFP measurements did not reveal any statistically significant difference at baseline and postoperative week 6 (P > 0.05 for all). However, at postoperative week 1, a significant difference (P = 0.047) was observed between the two groups. The mean LFP level was observed to be higher in Group 1 (24.16 ± 6.51 ph/ms) than in Group 2 (21.13 ± 5.23 ph/ms) [Table 3]. Moreover, a comparison of the LFP level from week 1 and the baseline measurement revealed a statistically significant difference between the two groups, with group 1 (8.27 ± 3.91 ph/ms) exhibiting a higher LFP difference than group 2 (4.86 ± 2.31 ph/ms) (P = 0.013).

Discussion

This study showed that nepafenac 0.3% administered once daily was as effective as nepafenac 0.1% given three times a day in preventing and treating ocular inflammation and cystoid macular edema following routine cataract surgery in patients with PEX. These findings align with those of two previous studies that compared two doses after uneventful phacoemulsification.[22,23] In contrast to other studies, our investigation exclusively encompassed patients with PEX.

Patients with PEX exhibit a compromised BAB, which results in elevated levels of inflammation after phacoemulsification.[9,10] Despite the existence of numerous clinical trials that have assessed the impact of topical NSAIDs on ocular inflammation following cataract surgery, data pertaining to patients with PEX remain scarce, particularly given the absence of studies that have compared the efficacy of two different nepafenac doses in this patient population. Previous research has demonstrated the efficacy of NSAIDs in attenuating inflammation when initiated before surgical procedures (1–3 days).[24] In particular, in high-risk populations (e.g., individuals with diabetes, PEX, uveitis, etc.), these agents play a pivotal role in regulating postoperative inflammation.[25,26]

The anterior chamber flare values of patients with PEX have been shown to be elevated.[27] Furthermore, NSAIDs have been demonstrated to result in a notable reduction in these values during the postoperative period.[28] Our study’s results revealed that both baseline and 6-week LFP measurements followed a similar pattern. In postoperative week 1, the mean LFP was significantly lower in the 0.3% nepafenac group compared to the 0.1% nepafenac group. These findings may be linked to nepafenac’s mechanism of action and its preoperative use, which has been shown to diminish inflammation caused by surgical trauma. It is expected that the higher concentration of 0.3% nepafenac in tissues before surgery will more effectively inhibit cyclooxygenase enzyme activity, mitigate the inflammatory response, and support the resolution of inflammation induced by the trauma. Therefore, nepafenac 0.3% may have been more effective in suppressing inflammation compared to nepafenac 0.1% in the immediate postoperative period. The study conducted by Bardoloi et al.,[23] similar to our own investigation, indicated that nepafenac 0.3% yielded considerably superior outcomes in terms of pain and inflammation management on days 1 and 7. In a previous study comparing nepafenac 0.3% and nepafenac 0.1%, it was determined that both groups demonstrated significantly superior outcomes in terms of inflammatory control compared to the vehicle control. In addition, nepafenac 0.3% exhibited comparable efficacy to nepafenac 0.1%.[22]

Several studies have demonstrated the impact of NSAID use on both CMT and MV in patients undergoing cataract surgery.[28,29,30] Our findings revealed that MV and CMT exhibited comparable levels in both groups across all visits. However, the study conducted by Bardoloi et al.[23] demonstrated that CMT in the group administered 0.3% nepafenac exhibited a significant reduction compared to the 0.1% nepafenac group during the first and third months. The discrepancy may be attributed to the inclusion of patients with PEX in our investigation, in addition to the fact that both groups received the same steroid treatment, which differs from that used in the previous study.

To the authors’ knowledge, this study is the first to compare the effectiveness of a once-daily 0.3% nepafenac regimen with a three-times-daily 0.1% nepafenac regimen in patients with PEX who have undergone cataract surgery. Nonetheless, the study has a number of limitations, including its retrospective design and the relatively small size of the sample. The retrospective design of the study also limited the ability to analyze certain parameters, such as pain scores, lid edema, corneal edema, grading of anterior chamber inflammation, and randomization of patients.

Conclusion

No significant difference was observed between the groups in CMT and anterior chamber LFP measurements at week 6. However, week 1 LFP measurements were found to be significantly lower in the nepafenac 0.3% group. Considering the ease of use and the fact that the majority of cataract patients are elderly, 0.3% nepafenac administered as a single daily dose may be a more advantageous option than 0.1% nepafenac administered three times a day after routine cataract surgery in patients with PEX.

Ethical approval

This study obtained ethical clearance from the Basaksehir Cam and Sakura City Hospital Ethics Committee (reference number: 2024-201) with the 1964 Helsinki Declaration.

Consent to participate

Written informed consent was provided by all subjects in accordance with the principles of the Helsinki Declaration.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.