The present retrospective study was performed to evaluate the effectiveness of topical NSAIDs and corticosteroids for the treatment of pseudophakic macular edema in real-life clinical practice. In over 80% of the patients, the macular edema was successfully resolved by following the treatment algorithm described in Fig. 1. Of the 33 cases, 19 (57.6%) resolved (no intraretinal or subretinal fluid) with topical NSAIDs after 2 to 9 months of treatment. Median BCVA improved significantly from 0.5 to 0.3 and CRT decreased significantly from 435 to 316 μm. Of the 13 eyes that received second-line corticosteroid treatment, the edema resolved in 9 eyes (69.2%), with a non-significant improvement in median BCVA (from 0.7 to 0.4), and a significant decrease in CRT (from 492 to 317 μm) and CCT (from 204 to 182 μm). Intravitreal dexamethasone implant was effective even in a case that had not responded previously to topical NSAIDs and peribulbar triamcinolone.
Guclu et al. [22] applied a 3 month course of topical nepafenac 0.1% four times a day in 30 eyes with PME, reporting a significant improvement in ETDRS BCVA from 20.9 to 32.9 letters (logMAR scale: approximately 1.3 to 1.1) and a significant decrease in CRT from 501.2 to 364.9 μm after 6 months. However, the resolution rate of macular edema was not reported.
Yüksel et al. [23] applied a 12 week course of topical nepafenac 0.1% three times a day in 24 eyes with PME, reporting a significant logMAR BCVA improvement from 0.84 to 0.37, and a significant decrease in CRT from 483.7 to 278.0 μm after 6 months. The edema resolved in all patients.
In our study, 33 eyes received once-daily topical nepafenac 0.3% for at least 2 months. Median BCVA improved significantly from 0.5 to 0.3 and CRT decreased significantly from 435 to 316 μm. The resolution rate of macular edema was 57.6%.
Bellocq et al. [13] applied intravitreal dexamethasone implant in 58 eyes with PME. Of these, 14% were treatment-naïve, while the others had received previous treatments (topical NSAIDs, oral acetazolamide, intravitreal or subconjunctival triamcinolone, intravitreal anti-VEGF). The study included patients with macular edema after cataract and several other types of surgery. Twelve months after a mean of 1.7 injections, the ETDRS BCVA improved significantly from 58.5 to 71 letters (logMAR scale: approximately 0.55 to 0.3) and CRT decreased significantly from 518.3 to 342.7 μm. Intraocular pressure > 25 mmHg was observed in 6.2% of the patients, but no filtering surgery was required. The specific resolution rate of macular edema for PME at 12 months was not reported. Abdolrahimzadeh et al. [15] applied intravitreal dexamethasone implant in 10 eyes with PME after uncomplicated phacoemulsification. The patients were unresponsive to topical steroids and NSAIDs. Five patients showed recurrence after one intravitreal dexamethasone implant and they received a second implant at month 7. After a twelve-month follow-up, the ETDRS BCVA improved significantly from 62 to 79 letters and CRT decreased significantly from 622 to 282 μm. Two patients were excluded from the study, and intraocular pressure remained stable during the follow-up. Furino et al. [16] applied a single injection of intravitreal dexamethasone implant in 11 eyes with PME after uncomplicated phacoemulsification. Six months later, BCVA improved significantly from 20/40 to 20/22 and CRT decreased significantly from 462 to 276 μm. Intraocular pressure did not increase significantly during the follow-up.
Erden et al. [12] applied a single injection of 40 mg subtenon triamcinolone in 21 treatment-naïve eyes diagnosed with PME. In that study, logMAR BCVA improved significantly from 0.71 to 0.24 and CRT decreased significantly from 431 to 299 μm after 6 months. The edema resolved in 90% of patients. Although the intraocular pressure increased slightly, this increase was not statistically significant.
In our study, 13 eyes received second-line corticosteroid treatment (intravitreal dexamethasone implant or peribulbar triamcinolone) after a course of at least 2 months of topical NSAIDs. The edema resolved in 9 eyes (69.2%), with a non-significant improvement in median BCVA (from 0.7 to 0.4), and a significant decrease in CRT (from 492 to 317 μm).
In our series, macular edema resolved in 84.8% of 33 eyes treated in accordance with our treatment algorithm (Fig. 1). To our knowledge, this is the first study of PME to describe a specific treatment algorithm and the success rate. Importantly, the effectiveness of corticosteroid treatment in our series could have been underestimated because these second-line treatments were applied in recalcitrant cases that failed to respond to a previous course of topical NSAIDs. In addition, in these cases, the PME had been present for an extended period of time, and the duration of PME may hinder fluid resolution and recovery of BCVA [10, 24]. In this regard, most of the patients treated with corticosteroids showed some degree of disruption of the external retinal layers on SS-OCT, which could explain why BCVA did not improve significantly (despite a clear trend towards improvement) even though both retinal and choroidal thicknesses decreased and the edema resolved in most of these cases. Considering these results, we can hypothesize that could be a very effective first-line option for PME, but we cannot confirm this supposition based on our study.
It is worth noting that we administered triamcinolone through the peribulbar route whereas other studies have used the subtenon route [12, 23]. As a result, it is difficult to directly compare our findings in these patients with other studies. To our knowledge, these two routes of administration have not been previously compared in PME.
The effectiveness of topical NSAIDs could have been underestimated in our study given that results were evaluated after an initial two-month course of treatment (although treatment was continued if some improvement was noted). By comparison, most studies that have evaluated the effectiveness of topical NSAIDs in PME have administered a three-month course of treatment [22, 23].
To date, no randomized trials have been performed to assess the optimal therapeutic protocol for PME. However, our treatment algorithm is a common approach to the management of PME [9, 10]. Since all of the patients were treated at the same ophthalmology department, the clinical management protocol was the same in all cases, performed in accordance with common criteria. This homogeneous management approach further strengthens the internal validity of our study.
Compared to other studies, the present case series is relatively large, particularly considering the single-institutional nature of the study [11, 12, 15, 16, 18, 19].
In addition, this is the first study to evaluate choroidal thickness in PME using SS-OCT. Other studies have previously evaluated choroidal thickness in PME using spectral domain OCT (SS-OCT) [25,26,27,28]. However, to the best of our knowledge, our study is the first one to evaluate choroidal thickness in PME using Swept-Source OCT. SS-OCT devices use longer wavelengths than spectral domain ones (1050 nm versus 840 nm). As a result, they experience less light scattering on the choroid and produce more precise images of the choroid. Besides, in our study we have utilized the application of the Triton SS-OCT to define automatically the limits of the choroid, while SD-OCT devices need the operator to manually establish the limits of the choroid in every case. This fact could cause a subjective bias when using SD-OCT to measure choroidal thicknesses, while SS-OCT has proved to be highly reproducible [29,30,31].
Importantly, we found that CCT decreased significantly after corticosteroid treatment, a finding that appears to support the hypothesis regarding the role of inflammation in PME, which may lead to the disruption of the blood-retina barrier and thus increased vascular permeability and fluid accumulation [7, 8]. Interestingly, this decrease in choroidal thickness was not evidenced in patients treated with topical NSAIDs, potentially due to the greater effectiveness of intravitreal dexamethasone implant [22]. Although peribulbar triamcinolone can resolve PME in cases that fail to respond to topical NSAIDs, one study found no statistically significant difference between the two treatments in terms of CRT in patients with PME [23]. The changes in CCT could shed light on the pathophysiology of PME and guide new treatments and future management of PME, if the association between inflammation and PME is confirmed. The decrease in CCT that we observed in eyes treated with corticosteroids could indicate an association between PME and the pachychoroid spectrum, with choroidal thickness being elevated in PME as occurs in central serous chorioretinopathy or aneurismal type 1 neovascularization [32], but further studies are needed to verify this hypothesis.
Study limitations
One limitation of this study is the sample size (33 eyes). Although this is larger than many of the studies on PME carried out to date, it is still insufficient to draw any definitive conclusions. Another potential limitation is the evaluation of the corticosteroid treatment, as corticosteroids were only administered in cases refractory to topical NSAIDs after several months of treatment. This could have negatively influenced the effectiveness of corticosteroid treatment in terms of resolution of the edema and final BCVA compared to upfront, first-line treatment with corticosteroids. However, this treatment sequence is widely used in ophthalmology to treat PME because NSAIDs are less invasive and have fewer side effects.