
Central serous chorioretinopathy (CSC) is characterized by posterior pole neurosensory retinal detachment caused by active retinal pigment epithelium (RPE) leakage [1,2]. The condition has been associated with corticosteroid use, type A personality, organ transplantation, pregnancy, hypertension, and psychopharmacologic medication use [3]. Affected patients complain of vision deterioration, including blurred vision, metamorphopsia, relative central scotoma, and micropsia. Fortunately, most cases of CSC are self-limiting, and serous retinal detachment (SRD) typically resolves spontaneously within 3-4 months [4-6]. Therefore, observation with or without removal of risk factors is one of the mainstays of therapy for acute CSC. However, in some cases, CSC can recur and often results in progressive vision loss [6-9]. Thus, early interventions should be considered in CSC patients, before disruption of the retinal layers.
Researchers have demonstrated that choroidal vasculopathy plays a significant role in the pathogenesis of CSC, with studies finding evidence of hyperpermeability from the choriocapillaris during fluorescein angiography in eyes with CSC [10-12]. However, the exact pathogenesis of CSC is not fully understood, although it has been hypothesized that choroidal hyperpermeability with secondary RPE dysfunction plays a significant role. Because of its unknown etiology, there is no standardized treatment protocol for CSC. Various treatment modalities, including observation, corticosteroid discontinuation, photodynamic therapy (PDT), selective retinal therapy, standard laser photocoagulation, intravitreal anti-vascular endothelial growth factor therapy, and systemic medications (e.g., carbonic anhydrase inhibitors, β-blockers, and aldosterone antagonists), are being used. However, none of these treatments are the gold standard, and some can have unwanted complications [13-17].
In such circumstances, topical non-steroidal anti-inflammatory drug (NSAID) could be a safe and effective solution for the treatment of CSC. In a previous study [18], it was suggested a topical NSAID as an acute CSC treatment with fewer complications and comparable efficacy, demonstrating an increase in visual acuity and decrease in SRF and SCT after topical pranoprofen treatment. NSAIDs inhibit cyclooxygenases and decrease prostaglandin production [19-24]. The drug type may inhibit choroidal inflammation and ischemic processes involved in CSC pathogenesis. However, although numerous studies of the effects of topical NSAID in acute CSC have been reported, few compare the effects between NSAIDs. Therefore, this study aimed to compare the effects of two different types of NSAIDs.
Using optical coherence tomography (OCT) parameters and visual acuity analysis, this study compared the clinical and structural efficacy of topical pranoprofen 0.1% and bromfenac 0.1% in acute CSC.
We conducted a retrospective study of 185 patients diagnosed with acute CSC for the first time and treated with topical NSAIDs. All subjects were seen at the hospital between January 2014 and October 2022. This study was approved by the institutional review board and ethics committee of the Dong-A University Hospital (no. DAUHIRB-23-115), and all study conduct adhered to the tenets of the Declaration of Helsinki. Informed consent was waived due to the retrospective nature of the study.
The diagnosis of CSC was based on the presence of SRD at the macula confirmed by OCT and focal leakage from the RPE on fluorescein angiography (FAG). Patients who met all the following inclusion criteria were included: 1) first CSC episode with symptoms presenting less than six weeks before diagnosis; 2) presence of SRF under the fovea as seen on OCT and active fluorescein leakage on FAG, and 3) a follow-up period longer than 3 months since the first visit. Exclusion criteria were as follows: 1) history of ocular disorders other than CSC that could affect the macula or the posterior retina (e.g., diabetic retinopathy, macular degeneration, choroidal neovascularization), 2) prior treatment for CSC (e.g., intravitreal injections, PDT, focal laser photocoagulation), and 3) known or suspected hypersensitivity to NSAID formulations.
All enrolled patients were divided into two groups according to topical NSAID formulations: the Pranopulin® (Pranoprofen ophthalmic, 0.1%; JW Shinyak Corp.) group and the Bronuck® (Bromfenac ophthalmic, 0.1%; Taejoon) group. The patients in both groups instilled one drop of the medication four times a day (QID).
All patients underwent a full ophthalmological evaluation, which included best-corrected visual acuity (BCVA) measurement, slit lamp examination, fundus examination, OCT, and FAG at the first visit. Follow-up examinations were performed at 1 and 3 months after the initiation of treatment and included BCVA measurement, dilated fundoscopy, and OCT assessment. The primary outcomes were changes in BCVA, subfoveal choroidal thickness (SCT), and maximum height of SRF after therapy.
Visual acuity was measured with a Snellen chart and converted to the logarithm of the minimum angle of resolution (logMAR) for data analysis. SCT and SRF values were obtained from a spectral-domain OCT system (Cirrus HDOCT; Carl Zeiss Meditec) or a swept-source OCT system (PLEX® Elite 9000; Carl Zeiss Meditec) obtained by the EDI-OCT maneuver. SCT was defined as the vertical distance from the hyperreflective line of Bruch’s membrane to the innermost hyperreflective line of the chorio-scleral interface. The maximum height of SRF was defined as the greatest distance between the outer surface of the neuroretina and the inner surface of the RPE layer at the neurosensory detachment. All OCT values were measured manually using a caliper included in the software by two blinded investigators (E.J. and Y.H.) and tested by calculating the intraclass correlation coefficient to assess consistency.
The statistical analyses were performed using SPSS® version 18.0 (IBM Corp.). Categorical variables were analyzed using the chi-square test or Fisher’s exact test. Student’s t test or Mann–Whitney U test was used to analyze continuous variables. The independent t test was used to compare continuous variables between two groups, and the pairedt test was used for comparisons within groups. Data were considered statistically significant at p-values < 0.05.
Clinical charts from 185 eyes with CSC were reviewed, with 101 eyes treated with topical pranoprofen 0.1% and 84 eyes t reated w ith t opical b romfenac 0.1%. D emographic characteristics, baseline visual acuity, and OCT values of the pranoprofen and bromfenac groups are shown in Table 1. The average age of patients was 45.74 ± 10.83 years in the pranoprofen group and 49.96 ± 11.97 years in the bromfenac group (p-value = 0.013). The mean BCVA of study eyes at baseline was 0.23 ± 0.25 and 0.17 ± 0.18 in the pranoprofen and bromfenac groups, respectively. There were no significant differences in gender, baseline BCVA, SCT, or maximum height of SRF between the two groups (Table 1).
In the pranoprofen group, there was a significant improvement in visual acuity at 1 month after treatment compared to baseline (p = 0.002). At 3 months of treatment, the improved visual acuity persisted (p = 0.000). In the bromfenac group, the mean BCVA improved significantly from baseline (1 month: p = 0.000; 3 months: p = 0.000) (Table 2). Changes in the mean BCVA between two groups at 1 and 3 months were not significant (p = 0.998, p = 0.540, respectively) (Table 3). In addition, although there was no statistically significant difference in the baseline SCT between the two groups (384.33 ± 80.97 μm in the pranoprofen group and 411.35 ± 107.90 μm in the bromfenac group, p-value = 0.060), the baseline SCT showed relatively high results in the bromfenac group. Therefore, it was necessary to further confirm if there were variations in the relative change compared to baseline SCT. When comparing the delta SCT/baseline SCT ratio, the delta SCT/baseline SCT ratio at 1 month after treatment was 0.035 ± 0.047 in the pranoprofen group and 0.059 ± 0.047 in the bromfenac group, still showing a significant difference between the two groups (p = 0.000). Similarly, at 3 months after treatment, the ratio was 0.041 ± 0.049 in the pranoprofen group and 0.072 ± 0.067 in the bromfenac group, showing a significant difference (p = 0.001).
The mean subfoveal choroidal thickness decreased significantly at 1 and 3 months in the pranoprofen group (p = 0.000 and p = 0.000, respectively) and the bromfenac group (p = 0.000 and p = 0.000) (Table 2). SCT reductions in the two groups were 13.35 ± 16.36 μm and 24.26 ± 20.54 μm at 1 month, respectively, and 16.15 ± 17.66 μm and 29.18 ± 29.49 μm at 3 months, a significant difference (p = 0.000 and p = 0.001) (Table 3). In addition, although there was no statistically significant difference in the baseline SCT between the two groups (384.33 ± 80.97 μm in the pranoprofen group and 411.35 ± 107.90 μm in the bromfenac group, p-value = 0.060), the baseline SCT showed relatively high results in the bromfenac group. Therefore, it was necessary to further confirm if there were variations in the relative change compared to baseline SCT. When comparing the delta SCT/baseline SCT ratio, the delta SCT/baseline SCT ratio at 1 month after treatment was 0.035±0.047 in the pranoprofen group and 0.059 ± 0.047 in the bromfenac group, still showing a significant difference between the two groups (p = 0.000). Similarly, at 3 months after treatment, the ratio was 0.041 ± 0.049 in the pranoprofen group and 0.072 ± 0.067 in the bromfenac group, showing a significant difference (p = 0.001).
The mean maximum height of SRF decreased significantly at 1 and 3 months in the pranoprofen group (p = 0.000 and p = 0.000, respectively) and the bromfenac group (p = 0.000 and p = 0.000) (Table 2). Changes in maximum height of SRF were 86.74 ± 104.48 μm and 104.81 ± 107.08 μm at 1 month and 138.66 ± 133.11 μm and 163.54 ± 136.24 μm at 3 months in the pranoprofen and bromfenac groups, respectively. There was no significant difference between the two groups regarding reabsorption of SRF (1 month: p = 0.248; 3 months: p = 0.212) (Table 3).
No serious adverse events were reported.
CSC is an idiopathic SRD secondary to increased permeability of choroidal vessels and leakage of fluid through impaired retinal pigment epithelial detachment [1,2]. Since prolonged detachment of the neurosensory retina is associated with PRE cells and photoreceptor atrophy, leading to irreversible loss of vision [6-9], various therapeutic approaches have been tried to avoid a chronic course and reduce progressive anatomical and functional loss. However, none of the treatments have shown superiority, and some can have unwanted complications. In this regard, topically applied NSAIDs could be an alternative, safe treatment option.
Topical NSAIDs inhibit the expression of cyclooxygenase enzymes, reducing endogenous production of prostaglandins, which act on the iris and ciliary body to induce vasodilation, blood-ocular barrier disruption, and pain. Topical NSAID has conventionally been used in the field of ophthalmology to control postoperative pain and posterior segment inflammation diseases, including uveitis, cystoid macular edema, and CSC.
Various reports have shown that patients treated with topical NSAIDs had a significantly faster resolution of SRF and improved visual acuity [18-22]. In a previous study [18], we reported that CSC patients that were treated with topical pranoprofen 0.1% showed a rapid improvement in visual acuity, SRF, SCT, and central macular thickness compared to the observation group. Khan et al. [19] demonstrated that topical bromfenac drops (one drop twice daily) returned macular thickness and visual acuity to near normal levels within 10 days. Our present results were similar to those of previous studies and supported the significant efficacy of topical NSAIDs on functional and anatomical recovery in acute CSC patients.
Although there has been a growing body of research that explores the effectiveness of NSAID eye drops in the treatment of CSC, there are few studies that compare the efficacy of NSAID formulations. Indeed, anti-inflammatory potency and the amount of drug penetration into ocular tissues can vary by formulation, and it would be worthwhile to compare the effectiveness of different NSAIDs in the treatment of CSC. This study, for the first time, compared two kinds of topical NSAIDs, pranoprofen and a relatively newly-approved bromfenac, in CSC patients. Our results show that bromfenac 0.1% QID is statistically superior in reducing SCT than pranoprofen 0.1% QID, while the two treatments were equally effective in improving BCVA and resolving SRF.
A key mechanism of action of NSAIDs on choroidal thickness involves the reduction of prostaglandin synthesis. Ogawa et al. [23] reported that bromfenac inhibited the production of prostaglandins from the rabbit iris-ciliary body by 50% at a concentration of 1.1 μM and was 10.9 times more potent than pranoprofen. Hayasaka et al. [24] revealed that a single instillation of bromfenac sodium 0.1% and pranoprofen 0.1% 1 hour before PGE2 application inhibited 33 ± 7 and 15 ± 7% of PGE2-induced flare elevation, respectively. In addition, bromfenac sodium had stronger anti-inflammatory potency than pranoprofen. Differences in penetration rate by ocular surface can also affect results, likely due to differences in the pharmacodynamic and pharmacokinetic properties of pranoprofen and bromfenac. Pranoprofen is a propionic acid derivative that possesses strong anti-inflammatory and analgesic properties, and bromfenac is an NSAID formulation with a bromine atom at the C4 of the benzoyl ring position. Bromfenac’s chemical structure lengthens the duration of anti-inflammatory activity and enhances its absorption into the ocular tissues. The non-metal bromine modifies the properties of the structure to which it is bound and fosters penetration of cell membranes. In consequence, bromfenac would penetrate easier or faster into the eye than other NSAID formulations [25].
This study has some limitations: First, despite literature reports of adverse effects on the ocular surface epithelium due to the use of NSAIDs, our results showed no adverse effects. We attributed this to the small number of patients and the short follow-up duration. Second, SCT and SRF values were obtained from two kinds of OCT systems: a spectral-domain and a swept-source OCT system. Such a comparison has been shown to be valid in earlier studies that demonstrated a nonsignificant choroidal thickness difference between these two machines [26-28]. Third, there is a significant difference in the average age between the two groups, which may cause discrepancy in demographic characteristics. Fourth, there was no placebo control group to reflect the natural course of the disease involving spontaneous resolution. Fifth, risk factors that may affect the progression of the disease, such as corticosteroid use, stress, smoking, alcohol consumption, and hypertension, were not considered. Sixth, numerous studies have previously reported on the diurnal change in choroidal thickness, which ranges from 20 to 30 μm [29,30]. However, in our current analysis, SCT measurements were not obtained at the same time across sessions, which may have distorted the results. Finally, the extent of initial SCT reduction is known to be associated with future relapse [31]. But we didn’t include data on relapse because, unlike relatively defined treatment frequencies such as anti-VEGF injections or PDT laser therapy, the duration of eye drop treatment varies among patients, making it challenging to accurately analyze recurrence rates.
In conclusion, our results are in line with the findings of earlier studies that demonstrate promising functional and anatomical effects of topical NSAID formulations with no critical tissue damage in CSC patients. Further, this is the first clinical study comparing topical pranoprofen and bromfenac, which were relatively recently commercialized for the treatment of acute CSC. We found topical bromfenac to have statistically greater efficacy than topical pranoprofen in terms of reduction of SCT, which may reflect disease activity and the possibility of recurrence. Thus, our results could help clinicians make better decisions in treatment of acute CSC patients. Further studies with a longer follow-up period and an adequate number of patients are necessary to determine the efficacy of the drugs.
This study was approved by the Institutional Review Board of Dong-A University Hospital (DAUHIRB-23-115).
The authors declare no conflicts of interest relevant to this article.
Conception (Y.H.K.); Design (Y.H.K.); Data acquisition (E.J.K., Y.H.K.); Analysis (E.J.K., Y.H.K.); interpretation (E.J.K., Y.H.K.); writing (E.J.K.); review (Y.H.K.); Final approval of the article (All authors).
![]() |
![]() |