Comparison of topical nepafenac 0.1% and 0.3% for the treatment of pseudophakic cystoid macular edema following cataract surgery

Abstract

Purpose

To compare the effectiveness of topical nepafenac 0.1% and 0.3% in the management of pseudophakic cystoid macular edema (PCME) following cataract surgery.

Methods

In this retrospective comparative study, patients with PCME after cataract surgery and a follow-up of at least three months were included. Patients were assigned to two groups according to the topical nepafenac treatment initiated after PCME diagnosis: 0.1% (Group-1) or 0.3% nepafenac (Group-2). Best-corrected visual acuity (BCVA), macular and choroidal parameters assessed by optical coherence tomography (OCT) were evaluated at diagnosis and during follow-up and were compared between the groups.

Results

The study included 97 eyes from 78 patients, with a mean age of 71.3 ± 7.1 years. Baseline demographic characteristics and surgical parameters were comparable between the groups. BCVA, macular and choroidal parameters improved in both groups during follow-up. At the third month, Group-1 showed significantly better mean BCVA (0.056 ± 0.082 vs. 0.122 ± 0.135, p = 0.028). At the first month, mean central foveal subfield thickness was significantly thinner in Group-1 (348.0 ± 96.5 vs. 387.9 ± 130.7, p = 0.047). Mean choroidal vascular index (CVI) increased during follow-up in both groups, with a greater increase observed in Group-2 at the first month (0.5 ± 2.7 vs. 2.1 ± 3.7, p = 0.024). Complete anatomical response at the first month was observed more often in Group-1 (60.0% vs. 38.1%, p = 0.033).

Conclusion

Topical nepafenac 0.1% and 0.3% were both associated with improvement in PCME. Group-1 showed better early anatomical and later visual outcomes, whereas Group-2 showed a greater early CVI increase. However, these findings do not establish the superiority of either regimen.

Introduction

Pseudophakic cystoid macular edema (PCME), or Irvine–Gass syndrome, is a common cause of decreased vision following cataract surgery [1]. Reported risk factors for PCME include young age (< 65 years), male gender, history of PCME in the contralateral eye, diabetes mellitus (DM), and complicated cataract surgery [2, 3]. While the incidence of PCME is higher in the presence of risk factors, the reported incidence of clinically significant vision loss associated with PCME ranges from 1.17% to 4.04% [4].

Increased postoperative inflammatory mediators in the aqueous and vitreous are thought to lead to PCME by disrupting the blood–aqueous and blood–retinal barriers [5]. Increased vascular permeability causes fluid to leak from perifoveal capillaries, forming cystic spaces in the center of the macula, particularly in the outer plexiform and inner nuclear layers, leading to the development of PCME [1].

Treatment approaches for PCME, including topical, peri- and intraocular steroids, topical nonsteroidal anti-inflammatory drugs (NSAIDs), and anti–vascular endothelial growth factor agents, and carbonic anhydrase inhibitors are used with varying success rates to suppress inflammation [6]. Nepafenac is a potent topical NSAID commonly used for this purpose, inhibiting inflammation-related disruption of the blood–retinal barrier and is available in concentrations of 0.1% and 0.3% [7, 8]. Previous studies have demonstrated that both concentrations of nepafenac are effective in controlling postoperative inflammation, preventing PCME, and treating PCME [8–11]. However, to the best of our knowledge, comparative data on different nepafenac concentrations in patients with PCME have not yet been reported in the literature.

The aim of this study was to compare the effectiveness of topical nepafenac 0.1% and 0.3% treatments in patients who developed PCME following cataract surgery.

Materials and methods

Study design

The medical records of patients undergoing cataract surgery with phacoemulsification and posterior chamber intraocular lens implantation at our clinic between January 2021 and June 2025 were retrospectively evaluated. The diagnosis of PCME was established based on a subjective decrease in visual acuity, together with optical coherence tomography (OCT) findings demonstrating increased central macular thickness and cystoid retinal changes. In cases where the diagnosis of PCME was uncertain, fundus fluorescein angiography (FFA) was performed to confirm the diagnosis. Among patients who developed PCME, those treated with topical nepafenac were selected and divided into two groups. Group-1 comprised patients treated with nepafenac 0.1% (Apfecto 0.1%; World Medicine Ophthalmics, UK), whereas Group-2 comprised patients treated with nepafenac 0.3% (Apfecto 0.3%; World Medicine Ophthalmics, UK). In both groups, topical nepafenac therapy was initiated after the diagnosis of PCME. In accordance with the approved standard regimen for each formulation, nepafenac 0.1% was administered three times daily and nepafenac 0.3% was administered once daily for at least 4 weeks. Treatment decisions were made based on the surgeons’ preference. All patients underwent standard phacoemulsification surgery and received a standardized postoperative treatment protocol. Accordingly, topical moxifloxacin 0.5% was administered four times daily for 10 days postoperatively, while topical prednisolone acetate 1% was initiated at four times daily and gradually tapered over four weeks. Routine topical NSAID prophylaxis was not used before the diagnosis of PCME. Topical nepafenac treatment was initiated only after PCME diagnosis.

The study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Istanbul University, Istanbul Faculty of Medicine Clinical Research Ethics Committee (Approval date and no: January 12, 2026; No. 3829850). All participants provided written informed consent before cataract surgery and subtenon injections.

Inclusion and exclusion criteria

Inclusion criteria were defined as: Having undergone cataract surgery at our clinic within three months before the diagnosis of PCME, presenting with clinical and OCT findings consistent with clinically significant PCME, having a follow-up duration of at least three months after PCME diagnosis, and having an axial length between 21.0 and 26.5 mm.

Exclusion criteria were defined as: Previous ocular trauma or intraocular surgery, epiretinal membrane, and a history or clinical evidence of retinal vein occlusion, pathologic myopia or myopic maculopathy, history of diagnosed uveitis, and the use of carbonic anhydrase inhibitors.

Age related macular degeneration (AMD) and DM were not considered exclusion criteria; however, those treated for exudative AMD or eyes with signs of diabetic retinopathy were excluded. In patients with DM, diabetic retinopathy was excluded based on dilated fundus examination and macular OCT findings; FFA was performed when clinically indicated or when the diagnosis was uncertain.

Outcomes

Patients’ demographic data (age, gender) and comorbid systemic diseases, including DM, hypertension, and benign prostatic hyperplasia (cases using alpha-adrenergic blockers) were recorded. During all follow-up visits, the best-corrected visual acuity (BCVA) value, detailed biomicroscopic anterior segment and fundoscopic examination findings were recorded. Nuclear cataract stage was classified into two groups based on the Lens Opacities Classification System III (LOCS III): stage ≤ 3 and stage ≥ 4 [12]. Axial length measurements were recorded. Intraoperative parameters, including the occurrence of surgical complications, the need for anterior vitrectomy, placement of a 10 − 0 nylon suture at the corneal incision, and intraocular lens position (in-the-bag or ciliary sulcus), were documented. The timing of PCME onset was recorded based on the postoperative week in which the diagnosis was established.

Retinal imaging was performed with Spectral-Domain OCT (Heidelberg Engineering, Germany) in infrared and OCT (IR&OCT) mode, providing simultaneous infrared and OCT imaging, with a 30° macular volume scan and automatic real-time (ART) image averaging enabled in retina scan mode. Enhanced depth imaging (EDI) mode was also activated for choroidal assessment and choroidal vascular index (CVI) analysis. OCT scans were repeated at the time of diagnosis of PCME and at first- and third-month follow-ups after topical nepafenac treatment.

Measurements included central macular thickness (CMT), defined as retinal thickness at the foveal center; central foveal subfield thickness (CST), defined as the mean thickness within the central 1-mm diameter area; and central choroidal thickness (CCT), defined as the subfoveal distance between the Bruch membrane and the inner scleral surface. Intraretinal cysts, subretinal fluid, hyperreflective foci, and the integrity of the outer retinal layers, external limiting membrane (ELM) and ellipsoid zone (EZ), were evaluated on the same scans. CVI was defined as the proportion of luminal area relative to the total choroidal area within the subfoveal area, using ImageJ software, as previously described [13]. All OCT measurements were obtained by two experienced ophthalmologists masked to the study groups. At the first- and third-month follow-up visits after PCME diagnosis, a complete anatomical response to treatment was defined as complete resolution of intraretinal cysts, absence of subretinal fluid, and a clinically meaningful decrease in CMT. Patients who were referred for additional treatment with subtenon steroid injection based on OCT findings at the third-month follow-up were recorded.

Statistical analysis

Statistical analysis was performed using the Number Cruncher Statistical System (NCSS, Utah, USA). All BCVA measurements were converted from Snellen lines to logarithmic minimum angle of resolution (logMAR) equivalents. Descriptive statistical methods were used to evaluate the data: mean, standard deviation, median, and interquartile range. Normality of data distribution was assessed using the Shapiro–Wilk test. Between-group comparisons were performed using the independent t-test for normally distributed variables and the Mann–Whitney U test for non-normally distributed variables, while categorical data were analyzed using the chi-square or Fisher’s exact test. A p value of < 0.05 was considered statistically significant.

Results

A total of 97 eyes (Group-1: 55; Group-2: 42) from 78 patients were included in the study. There were no statistically significant differences between the groups in terms of age, gender distribution, and accompanying systemic diseases (p > 0.05 for all). LOCS III–based nuclear cataract grade (≤ 3 vs. ≥ 4), ocular comorbidities, and intraoperative parameters were comparable between the groups (p > 0.05 for all). Table 1 presents the baseline demographic, clinical, and surgical parameters of the patients. The mean time to PCME development after cataract surgery was 5.9 ± 3.0 weeks, with no significant difference between the groups (5.8 ± 2.9 and 6.1 ± 3.1 weeks, respectively; p = 0.591).

Table 1.

Demographic, clinical and surgical parameters of the patients and intergroup comparisons

Mean ± SD or n - %		Total (n = 97)			Group-1 (n = 55)		Group-2 (n = 42)		p
Age (Year)		71.3 ± 7.1			71.7 ± 6.8		70.7 ± 7.6		0.518*
Sex	Male	60	61.9%		36	65.5%	24	57.1%	0.404**
	Female	37	38.1%		19	34.5%	18	42.9%
Eye	Right	56	57.7%		33	60.0%	23	54.8%	0.605**
	Left	41	42.3%		22	40.0%	19	45.2%
Diabetes Mellitus		30	30.9%		14	25.5%	16	38.1%	0.182**
Systemic Hypertension		56	57.7%		31	56.4%	25	59.5%	0.755**
Benign prostatic hyperplasia (α-blocker use) ***		13	21.7%		5	13.9%	8	33.3%	0.073**
LOCS III nuclear cataract stage	stage ≤ 3	66	68.0%		36	65.5%	30	71.4%	0.391**
	stage ≥ 4	31	32.0%		19	34.5%	12	28.6%
Axial Length		23.6 ± 1.0			23.6 ± 0.9		23.6 ± 1.1		0.811*
Glaucoma		11	11.3%		6	10.9%	5	11.9%	0.878**
PEX		15	15.5%		11	20.0%	4	9.5%	0.157**
AMD		9	9.3%		7	12.7%	2	4.8%	0.180**
Intraocular lens position	In-the-bag	81		83.5%	46	83.6%	35	83.3%	0.968**
	Ciliary sulcus	16		16.5%	9	16.4%	7	16.7%
Anterior vitrectomy		15		15.5%	8	14.5%	7	16.7%	0.775**
Corneal incision suturing (10 − 0 nylon)		28		28.9%	12	21.8%	16	38.1%	0.080**

SD: Standard deviation, PEX: Pseudoexfoliation, AMD: Non-exudative age-related macular degeneration, LOCS III: Lens Opacities Classification System III, PCME: Pseudophakic cystoid macular edema

*Independent t-test

**Chi-square test

***: Percentages calculated among male patients only

At the three-month follow-up after treatment, the mean BCVA was significantly better in Group-1 (p = 0.028; Table 2). Mean CMT and CST values decreased over time in both groups during the follow-up after PCME diagnosis. At the 1-month follow-up, mean CST differed significantly between the groups (p = 0.047). Mean CCT values did not differ significantly between the groups at the time of PCME diagnosis or during follow-up (p > 0.05 for all). CVI values were significantly higher in Group-1 at the time of PCME diagnosis and at the three-month follow-up (p = 0.006 and 0.047, respectively).

Table 2.

Visual acuity and optical coherence tomography parameters at pseudophakic cystoid macular edema diagnosis and during follow-up

Parameter	Time Point	Total (n = 97)	Group-1 (n = 55)	Group-2 (n = 42)	p
BCVA (LogMAR)	Preoperative	0.559 ± 0.372	0.571 ± 0.391	0.542 ± 0.348	0.886*
	Postoperative	0.109 ± 0.189	0.099 ± 0.116	0.123 ± 0.256	0.588*
	At PCME diagnosis	0.209 ± 0.212	0.204 ± 0.220	0.215 ± 0.202	0.588*
	Month 1	0.148 ± 0.191	0.116 ± 0.147	0.193 ± 0.233	0.292*
	Month 3	0.084 ± 0.111	0.056 ± 0.082	0.122 ± 0.135	0.028*
CMT (µm)	At PCME diagnosis	424.0 ± 149.3	411.4 ± 136.2	440.6 ± 165.1	0.343**
	Month 1	334.1 ± 139.6	316.1 ± 122.8	357.7 ± 157.4	0.147**
	Month 3	284.6 ± 89.5	268.5 ± 64.4	304.8 ± 111.3	0.088**
CST (µm)	At PCME diagnosis	442.6 ± 122.9	427.7 ± 108.9	462.7 ± 138.3	0.169**
	Month 1	365.3 ± 113.7	348.0 ± 96.5	387.9 ± 130.7	0.047**
	Month 3	323.2 ± 73.2	309.6 ± 55.8	339.7 ± 88.1	0.080**
CCT (µm)	At PCME diagnosis	225.5 ± 77.9	229.6 ± 68.6	220.1 ± 89.2	0.557**
	Month 1	215.7 ± 75.7	218.3 ± 68.9	212.3 ± 84.6	0.702**
	Month 3	206.5 ± 78.1	205.4 ± 70.0	207.7 ± 88.1	0.903**
CVI (%)	At PCME diagnosis	62.7 ± 3.6	63.6 ± 3.3	61.6 ± 3.6	0.006**
	Month 1	63.9 ± 3.0	64.2 ± 2.7	63.66 ± 3.4	0.409**
	Month 3	64.3 ± 3.3	65.0 ± 3.4	63.5 ± 3.1	0.047**

PCME: Pseudophakic cystoid macular edema, BCVA: Best-corrected visual acuity, LogMAR: Logarithm of the minimum angle of resolution, CMT: Central macular thickness, CST: central foveal subfield thickness, CCT: central choroidal thickness, CVI: choroidal vascular index

Bold: Statistically significant

*: Mann Whitney U test

**: Independent t-test

Table 3 shows the mean changes in visual acuity and OCT parameters at 1- and 3-months follow-up from the time of PCME diagnosis. No statistically significant difference was found between the groups in terms of changes in BCVA, CMT, CST, and CCT between the time of PCME diagnosis and the 1st and 3rd month controls (p > 0.05 for all). However, the change in CVI from the time of PCME diagnosis to 1 month was statistically significantly higher in Group-2 (p = 0.024). No significant between-group differences were observed in CVI changes at other follow-up intervals (p > 0.05).

Table 3.

Mean changes in visual acuity and optical coherence tomography parameters from pseudophakic cystoid macular edema diagnosis to 1- and 3-month follow-up

Parameter	Time Interval	Total (n = 97)	Group-1 (n = 55)	Group-2 (n = 42)	p*
BCVA (LogMAR)	PCME → Month 1	-0.062 ± 0.178	-0.088 ± 0.186	-0.025 ± 0.163	0.180
	PCME → Month 3	-0.130 ± 0.194	-0.146 ± 0.208	-0.108 ± 0.174	0.553
	Month 1 → Month 3	-0.059 ± 0.147	-0.053 ± 0.116	-0.068 ± 0.185	0.746
CMT (µm)	PCME → Month 1	-89.9 ± 160.9	-95.3 ± 135.7	-82.9 ± 190.5	0.595
	PCME → Month 3	-151.0 ± 155.7	-138.6 ± 128.6	-166.5 ± 185.2	0.614
	Month 1 → Month 3	-64.4 ± 111.2	-53.0 ± 106.9	-78.7 ± 116.5	0.274
CST (µm)	PCME → Month 1	-75.7 ± 129.9	-79.6 ± 108.5	-70.4 ± 155.4	0.512
	PCME → Month 3	-127.3 ± 124.4	-116.3 ± 99.0	-141.1 ± 150.9	0.683
	Month 1 → Month 3	-55.0 ± 87.4	-44.6 ± 78.2	-67.6 ± 97.1	0.313
CCT (µm)	PCME → Month 1	-9.8 ± 42.3	-11.3 ± 42.3	-7.9 ± 42.8	0.558
	PCME → Month 3	-17.2 ± 47.6	-23.5 ± 40.6	-9.6 ± 54.6	0.094
	Month 1 → Month 3	-7.1 ± 42.4	-14.3 ± 44.8	1.6 ± 38.0	0.065
CVI (%)	PCME → Month 1	1.2 ± 3.3	0.5 ± 2.7	2.1 ± 3.7	0.024
	PCME → Month 3	1.7 ± 3.4	1.7 ± 3.2	1.7 ± 3.7	0.737
	Month 1 → Month 3	0.4 ± 2.9	0.9 ± 2.3	-0.3 ± 3.5	0.061

PCME: Pseudophakic cystoid macular edema, BCVA: Best-corrected visual acuity, LogMAR: Logarithm of the minimum angle of resolution, CMT: Central macular thickness, CST: central foveal subfield thickness, CCT: central choroidal thickness, CVI: choroidal vascular index

Bold: Statistically significant

*: Mann Whitney U test

Table 4 shows the distribution of OCT-based retinal findings at the time of PCME diagnosis and at first and third months of follow-up visits. While intraretinal cysts were observed in all cases at the time of PCME diagnosis, both groups showed regression in terms of intraretinal cysts, hyperreflective foci, ELM/EZ disruption, and subretinal fluid presence during follow-up. When these parameters were evaluated individually, no statistically significant difference was observed between the groups (p > 0.05 for all). However, a significantly higher rate of complete anatomical response was observed in Group-1 at the first-month follow-up (p = 0.033). At the third-month follow-up, although complete anatomical response rates increased in both groups, the intergroup difference was not statistically significant (p = 0.236). At the end of the three-month follow-up period, one eye in Group-1 (1.8%) and three eyes in Group-2 (7.1%) showed an indication for subtenon steroid injection (p = 0.191).

Table 4.

Optical coherence tomography based retinal findings at PCME diagnosis and during follow-up

Parameter	Time Point	Total (n = 97)		Group-1 (n = 55)		Group-2 (n = 42)		p*
IRC	At PCME diagnosis	97	100.0%	55	100.0%	42	100.0%	N/A
	Month 1	42	43.3%	21	38.2%	21	47.6%	0.244
	Month 3	19	19.6%	9	16.4%	10	23.8%	0.360
HRF	At PCME diagnosis	12	12.4%	6	10.9%	6	14.3%	0.617
	Month 1	9	9.3%	5	9.1%	4	9.5%	0.942
	Month 3	7	7.2%	3	5.5%	4	9.5%	0.443
ELM / EZ disruption	At PCME diagnosis	35	36.1%	22	40.0%	13	31.0%	0.358
	Month 1	22	22.7%	12	21.8%	10	23.8%	0.816
	Month 3	11	11.3%	5	9.1%	6	12.3%	0.424
SRF	At PCME diagnosis	56	57.7%	30	54.5%	26	61.9%	0.467
	Month 1	31	32.0%	14	25.5%	17	40.5%	0.116
	Month 3	11	11.3%	4	7.3%	7	16.7%	0.148
Complete anatomical response	Month 1	49	50.5%	33	60.0%	16	38.1%	0.033
	Month 3	77	79.4%	46	83.6%	31	73.8%	0.236

PCME: Pseudophakic cystoid macular edema, IRC: Intraretinal cysts, HRF: Hyperreflective foci, ELM: External limiting membrane, EZ: Ellipsoid zone, SRF: Subretinal fluid, N/A: Not applicable

*: Chi-Square test

Bold: Statistically significant

Discussion

The pathophysiology, clinical findings, and efficacy of medications used in the treatment of PCME after cataract surgery have been evaluated in previous studies [2, 6, 14, 15]. Additionally, the efficacy of nepafenac in controlling inflammation and the treatment of PCME after cataract surgery has been demonstrated in various studies in the literature [9, 16, 17]. However, to the best of our knowledge, the literature does not include any study comparing the efficacy of different nepafenac eye drop concentrations in the treatment of PCME. In the present study, we evaluated the effects of topical nepafenac treatments at 0.1% and 0.3% concentrations on anatomical and functional outcomes in PCME. Our findings indicate that both concentrations are effective in the treatment of PCME. However, 0.1% nepafenac was associated with a higher rate of complete anatomical response in the early period and better visual acuity outcomes in the late period.

As three months is currently accepted as the threshold for distinguishing acute from chronic PCME, only patients who developed PCME within three months after cataract surgery were included, and follow-up after PCME diagnosis was limited to three months [14]. Common clinical conditions frequently encountered in PCME cases in routine practice, such as pseudoexfoliation, DM, use of alpha-adrenergic blockers, and complicated cataract surgery, were not considered exclusion criteria to maintain the generalizability of the study population [3, 18, 19]. However, no significant difference was observed between the groups in terms of the distribution of systemic and ocular comorbidities. In contrast, retinal diseases that could directly affect PCME pathophysiology and OCT-based measurements, including diabetic retinopathy, epiretinal membrane, and exudative AMD, were excluded from the study [3, 20].

Although PCME can lead to clinically significant vision loss, subclinical cases are now more frequently detected due to the widespread use of OCT [21]. In our clinic, OCT scans are performed in patients reporting subjective visual disturbances, even when visual acuity appears normal on the Snellen chart. This approach is also supported by previous studies recommending OCT evaluation in patients with subjective visual complaints, even when visual acuity is relatively preserved, rather than performing OCT in all postoperative cases [2, 22, 23]. This may explain why some patients diagnosed with PCME in our study had relatively preserved visual acuity at presentation. While there was no significant difference in BCVA between the groups at PCME diagnosis or at the first-month follow-up, Group-1 showed significantly better BCVA at the third-month follow-up. This finding may be related to the more frequent dosing of 0.1% nepafenac and thus the more balanced maintenance of the anti-inflammatory effect in retinal tissues over time. The thinner mean CST values observed in Group-1 at the first month of treatment suggest that early anatomical improvement may contribute to improved visual outcomes over time. However, anatomical and functional recovery in PCME may not always occur in parallel, as a reduction in macular thickness does not necessarily result in a proportional visual gain [24]. This may be explained by several factors, including baseline visual acuity, outer retinal integrity, residual inflammatory changes, and ocular comorbidities, all of which may influence final BCVA [25]. Sengupta et al. reported that in acute PCME cases, improvements in visual acuity were more limited in patients with poorer baseline vision and that anatomical recovery often preceded functional improvement [25]. Previous studies have also reported that differences in visual outcomes among various anti-inflammatory treatments for PCME become more apparent during longer-term follow-up [17, 26].

Our study findings show a consistent decrease in central macular thickness parameters during the follow-up period with both NSAID treatments. Inflammation plays a key role in the pathogenesis of PCME [6]. NSAID treatment reduces macular thickness by decreasing retinal vascular permeability and thereby provides an anatomical response [6]. Previous studies have also reported a significant decrease in macular thickness after topical nepafenac treatment in PCME patients, and this anatomical response may vary among cases [9, 27]. The observation of thinner CST values in the 0.1% nepafenac group in the early period in our study may suggest that dosing frequency could influence inflammation control at the foveal level. However, this difference was not significant in the long term. In addition, no significant difference was observed between the groups in the mean changes in CMT and CST between the time of PCME diagnosis and follow-up visits. These findings may suggest that the two nepafenac treatments provide comparable anatomical improvement in PCME treatment. In addition, the need for subtenon steroid injection was higher in Group-2, but the difference was not statistically significant. This finding may suggest that nepafenac treatments effectively controlled the anatomical response in PCME, while the need for subtenon steroid injection may vary independently of the treatment regimen.

OCT-derived macular morphological findings (IRC, HRF, ELM/EZ disruption, and SRF) showed no significant differences between the groups; however, the complete anatomical response, defined as regression of all findings, was significantly higher in Group-1 at the first month. More frequent dosing of nepafenac in the early stages of PCME may be associated with faster control of retinal edema. The absence of a significant difference between the groups in terms of complete anatomical response rates at the third month suggests that nepafenac treatments provide comparable long-term anatomical efficacy. In a preclinical study, it was reported that the levels of the active metabolite (amfenac) achieved in retinal tissue with 0.3% nepafenac administered once daily were lower compared to treatment with 0.1% nepafenac administered three times daily [28]. While this approach may be adequate for CME prophylaxis, it has been suggested to be insufficient for treating established CME [10]. Accordingly, in established postoperative CME, Giarmoukakis et al. [9] administered 0.3% nepafenac twice daily to achieve stable therapeutic levels, an approach that was associated with anatomical improvement.

When PCME develops, inflammation may not be limited to the retina and may also involve the choroid. Fleissig et al. [29] demonstrated that CCT increases during the acute phase of PCME and decreases following resolution of the edema. Similarly, in our study, mean CCT values decreased after treatment in both groups. However, no significant differences were observed between the groups in terms of mean CCT values or the changes in CCT values across follow-up visits. CVI, which reflects both the vascular and stromal components of the choroid, has recently gained attention as an indirect marker of choroidal vascular structure and inflammatory response [30, 31]. In our study, CVI increased during follow-up in both treatment groups. CVI values were significantly higher in Group-1 at PCME diagnosis and at the third-month follow-up, whereas no significant difference was observed between the groups at the first-month follow-up. Therefore, the greater early increase in CVI observed in Group-2 should be interpreted cautiously, considering the lower baseline CVI values in this group. Overall, these findings suggest that CVI may provide additional insight into choroidal changes during PCME treatment. However, because the two regimens differed in both nepafenac concentration and dosing frequency, the present study cannot determine the contribution of each factor to the observed CVI changes.

This study has several limitations. Due to the study’s retrospective design, selection bias cannot be excluded because the treatment groups were determined by surgeon preference rather than randomization. However, baseline demographic, clinical, and surgical characteristics were comparable between the groups. In addition, medication adherence could not be objectively assessed because of the retrospective design, and differences in dosing frequency between the two nepafenac treatments may have influenced treatment compliance. As no control or placebo group was included, the natural course of PCME could not be evaluated, and prospective randomized controlled studies are needed to confirm these findings. Although exudative AMD was excluded, the inclusion of non-exudative AMD cases may have affected BCVA and some OCT findings. The absence of additional functional assessments, such as contrast sensitivity, is another limitation. Although PCME diagnosis was based on characteristic OCT findings, FFA was not routinely performed, which may also be considered a limitation. Finally, objective anterior segment inflammation was not assessed using laser flare photometry. Nevertheless, to the best of our knowledge, this study is among the first to compare different approaches to nepafenac treatment for PCME.

In conclusion, both 0.1% and 0.3% nepafenac treatments were associated with improvements in cystoid macular edema and visual acuity in patients with PCME. The 0.1% nepafenac group showed a higher early complete anatomical response and better BCVA at the third-month follow-up, whereas the 0.3% nepafenac group showed a greater early increase in CVI. However, the between-group differences in the changes in BCVA and macular thickness parameters were not statistically significant during follow-up. Currently, there is no standardized treatment approach for PCME. These findings may contribute to the clinical understanding of different nepafenac regimens in PCME and support the need for prospective randomized studies to clarify their comparative effects.

Abbreviations

PCME

Pseudophakic cystoid macular edema

BCVA

Best-corrected visual acuity

OCT

Optical coherence tomography

CVI

Choroidal vascular index

DM

Diabetes mellitus

NSAID

Nonsteroidal anti-inflammatory drug

FFA

Fundus fluorescein angiography

AMD

Age-related macular degeneration

LOCS III

Lens Opacities Classification System III

ART

Automatic real-time

EDI

Enhanced depth imaging

CMT

Central macular thickness

CST

Central foveal subfield thickness

CCT

Central choroidal thickness

ELM

External limiting membrane

EZ

Ellipsoid zone

logMAR

Logarithm of the minimum angle of resolution

Author contributions

S.C. contributed to the conception and design of the study, data collection, analysis and interpretation, and drafting of the manuscript. M.S. and E.A. contributed to data collection, analysis, and drafting of the manuscript. Z.C., G.E., and Ş.B. contributed to data analysis and interpretation, supervision, and critical revision of the manuscript for important intellectual content. All authors approved the final version of the manuscript and agree to be accountable for all aspects of the work.

Funding

No funding or financial support was received for this study.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

The study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Istanbul University, Istanbul Faculty of Medicine Clinical Research Ethics Committee (Approval date and no: January 12, 2026; No. 3829850). All participants provided written informed consent before cataract surgery and subtenon injections.

Consent for publication

Not applicable.

Competing interests

The corresponding author is a member of the Editorial Board of BMC Ophthalmology and had no role in the editorial handling or peer review process of this manuscript.