Introduction
Pseudopahkic cystoid macular edema (CME) is a common cause of visual acuity reduction after cataract surgery (1–3). The main risk factors of macular edema is a intraoperative vitreous loss, ocular trauma, anterior chamber intraocular lens, intraocular postoperative inflammation. These factors cause the release of inflammatory mediators, including prostaglandins. These substances cause a cascade of inflammation and rupture of the blood-retinal barrier and macular edema formation in some patients (1, 3). Most patients are treated with topical steroids, nonsteroidal anti-inflammatory drugs (NSAIDs) for several months (1–3). Some patients with chronic edema are treated with intravitreal ranibizumab (4), sub-Tenon betamethasone (5) and subcutaneously interferon alpha (6) with good results. Despite of many new treatment methods in some patients macular edema persists for many months.
However, the effectiveness of ophthalmic solution of bromfenac for acute pseudophakic CME has been reported previously. We describe two cases with resolution of chronic pseudophakic CME after topical administration of bromfenac sodium ophthalmic solution 0.09% documented with spectral domain optical coherence tomography (SD-OCT, Spectralis, Heidelberg Engineering Inc).

Material and methods
A 79-year-old woman (patient 1) presented with decreased visual acuity and metamorphopsia in the left eye and 64-year-old men (patient 2) with decreased visual acuity and metamorphopsia in the right eye that had lasted for 6 months and after undergoing subluxated phacoemulsifiaction cataract surgery with anterior chamber lens implantation in another departments. Both of them had been initially treated unsuccessfully with combination of diclofenac 0.1%, prednisolone acetate 1% and with oral acetazolamide for as long as 6 months.
SD-OCT examination showed pseudophakic CME with subretinal fluid and elongation of the photoreceptors layer: distance before external limiting membrane (ELM) and most protruding outer segment of photoreceptors. SD-OCT image after initially treatment showed also a central retinal thickness of 440 μm in the patient 1 (Figure 1a) and a central retinal thickness of 577 μm in the patient 2 (Figure 2b). Best-corrected visual acuity (BCVA) was 20/40 in patient 1, and was 20/80 in patient 2. The administed eye drops were discontinued. Bromfenac sodium ophthalmic solution 0.09% (Yellox) was topically administered twice a day and monitored with SD-OCT images.

Results
Completly resolution of CME was noted after 2 months of topical therapy, with improvement of visual acuity. Central retinal thickness had improved to 220 μm and BCVA was 20/25 in patient 1 (Figure 1b) and central retinal thickness had improved to 233 μm and BCVA was 20/20 in patient 2 (Figure 2b). During 6 months follow-up there has been no recurrence of CME. There were no side effects noted after treatment.

Discussion
To our knowledge, the current cases are the first description of the rapid resolution of chronic pseudophakic cystoid macular edema after topical administration of 0.09% bromfenac clearly documented in SD-OCT.
Cataract surgery can cause a cascade of inflammation and breakdown of to the blood-retinal barrier. This can lead to development of psuedophakic CME – accumulation of intraretinal fluid in the outer plexiform and inner nuclear layers of the retina or subretinal (7, 8). Actually there are no approved drugs for the treatment of psuedophakic CME.
The bromfenac (Yellox) was approved in Europe in 2011 for the treatment of postoperative inflammation in patients after cataract surgery (9). Despite the fact that the drug is registred in Poland for the treatment of postoperative inflammantion, we decided to give it because we think that pseudophakic CME is secondary to postoperative inflammation. Another factor why we applied bromfenac was no improvement after use of topical diclofenac. The bromfenac has got a lipophilic molecule structure that cause rapidly drug penetration. It cease prostaglandyn’s synthesis especially COX-2 enzyme (10). The experiments on animals showed that bromofenac is 32 times stronger inhibiting COX-2 than COX-1 enzyme and 18 times stronger inhibits COX-2 than ketorolac (11). As we know COX-2 enzyme is the strongest inflammation mediator in humane being eye (12). However, Warren et al. showed the effectiveness of NSAIDs as an additional drug for patients treated with an intravitreal triamcinolone and bevacizumab injection because of chronic pseudophakic CME. In eyes treated additionaly with nepafenac and bromfenac retinal thickness reduced significantly in comparison to placebo (13). The another author presented that twice-daily bromfenac was statistically effectiveness that diclofenac or ketorolac dosed 4 times daily for the treatment of acute pseudophakic CME (14).
In our patients complete resolution of CME was observed after 2 months of topical therapy, with improvement in visual acuity. SD-OCT shows normal foveal contour and well-visible normal-thickness photoreceptor layer. These facts suggest that the main role in the development of pseudophakic CME may play COX-2 enzyme.

Conclusions
In summary, 0.09% bromfenac sodium ophthalmic solution has been demonstrated to as an effective treatment of chronic pseudophakic CME, but these results still remain unclear and needs further investigation.

References:
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Fig. 1a. Patient 1 – pseudophakic chronic cystoid macular edema (CME) before topical treatment of bromfenac solution. Spectral optical coherence tomography (SD-OCT) shows CME with subretinal fluid and elongation of the photoreceptors layer: distance before external limiting membrane (ELM) and most protruding outer segment of photoreceptors. Central retinal thickness was 440 μm.
Ryc. 1a. Pacjent nr 1 – pseudofakijny przewlekły torbielowaty obrzęk plamki przed leczeniem bromfenakiem. Spektralna optyczna koherentna tomografia (SD-OCT) pokazuje: torbielowaty obrzęk plamki, płyn pod siatkówką zmysłową, wydłużenie warstwy fotoreceptorów. Centralna grubość siatkówki wynosi 440 μm.



Fig. 2a. Patient 2 – pseudophakic chronic cystoid macular edema (CME) before topical treatment of bromfenac solution. SD-OCT shows CME with subretinal fluid and elongation of the photoreceptors layer. The hyper-reflective linear structure on the inner surface of the retina could be interpreted as a epiretinal membrane. Central retinal thickness was 577 μm. Ryc. 2a. Pacjent nr 2 – pseudofakijny przewlekły torbielowaty obrzęk plamki przed leczeniem bromfenakiem. W obrazie SD-OCT widać: torbielowaty obrzęk plamki, płyn pod siatkówką zmysłową, wydłużenie warstwy fotoreceptorów. Hiperefleksyjną linią na wewnętrznej powierzchni siatkówki może być błona nasiatkówkowa. Centralna grubość siatkówki wynosi 577 μm.



Fig. 1b. Patient 1 – pseudophakic chronic cystoid macular edema 6 months after bromfenac treatment. SD-OCT shows normal foveal contour, with completely resolution of CME, also shows well-visible normal-thickness photoreceptor layer without any defects. Central retinal thickness was 220 μm.
Ryc. 1b. Pacjent nr 1 – pseudofakijny przewlekły torbielowaty obrzęk plamki 6 miesięcy po miejscowym leczeniu bromfenakiem. W obrazie SD-OCT nie widać torbielowatego obrzęku plamki, widoczne są: prawidłowy kontur dołka i warstwa fotoreceptorów o normalnej grubości. Centralna grubość siatkówki wynosi 220 μm.



Fig. 2b. Patient 2 – pseudophakic chronic cystoid macular edema 6 months after bromfenac treatment. SD-OCT shows normal foveal contour, with completely resolution of CME, also shows well-visible normal-thickness photoreceptor layer without any defects. Central retinal thickness was 233 μm.
Ryc. 2b. Pacjent nr 2 – pseudofakijny przewlekły torbielowaty obrzęk plamki 6 miesięcy po miejscowym leczeniu bromfenakiem. W obrazie SD-OCT nie widać torbielowatego obrzęku plamki, widoczne są: prawidłowy kontur dołka i warstwa fotoreceptorów o normalnej grubości. Centralna grubość siatkówki wynosi 233 μm.