The common causes of CME include retinal vascular diseases, such as diabetic retinopathy, uveitis, post-intraocular surgery for conditions such as cataract, macular diseases such as vitreo-macular traction syndrome, retinitis pigmentosa, and use of eye drop formulations such as latanoprost [
8,
9]. However, none of these CME-causing conditions was observed in this case, leading us to conclude that CME had arisen as a complication of ICE syndrome. Kocaoğlan et al. have discussed the proliferation of abnormal endothelial cells in the iridocorneal angle and iris plane and the subsequent contraction of the membrane of proliferated cells contributing to the collapse of the inner blood-retinal barrier as a possible mechanism for the complication of ICE syndrome with CME [
5]. In addition, Fourmaux & Velasque have speculated that the mechanism of action may be similar to that in cases with CME after cataract surgery [
6]. In this case, we considered the following factors as a mechanism for the onset of CME as a complication of ICE syndrome. First, increasing use of swept-source optical coherence tomography in recent years has led to indications of a connection between the vitreous pocket and Cloquet’s canal [
10]. Further, in CME caused by use of an eye drop formulation of latanoprost, a prostaglandin analog used for glaucoma [
9] and CME following cataract surgery [
11], inflammatory material from the anterior chamber may reach the macula and lead to collapse of the inner blood-retinal barrier. Use of an eye drop formulation of diclofenac sodium (an NSAID) to prevent the development of CME after cataract surgery has proven to be effective [
11]. In this case, since topical nepafenac was effective against macular edema, we believe that prostaglandin-like material derived from abnormal endothelial cells may have reached the macula and contributed to the collapse of the inner blood-retinal barrier. A topical or systemic steroid is another candidate for treatment of CME, but we used topical nepafenac, because ICE syndrome often causes glaucoma. Only one of the previous case reports documented the method of treatment [
5], where both steroid and NSAID eye drops appeared to be ineffective. It is difficult to account for this discrepancy. It is possible that CME could have resolved in our patient as part of the natural history of this disorder, but previous cases did not include disappearance of CME, and we had observed our patient for 3 months without treatment and did not find improvement. Therefore, it is more likely that topical nepafenac eliminated the macular edema. This case suggests the possibility that NSAID eye drops could be effective for the treatment of CME accompanying ICE syndrome. However, we need more cases to confirm this possibility.
Finally, we need to address the issue of possible toxicity of NSAIDs to the cornea. Nepafenac-induced corneal graft melt was reported in one case with graft-versus-host disease [
12], and nepafenac-associated bilateral corneal melt was reported in one case where nepafenac was used in error every 2 h [
13]. Our patient and a previously reported patient treated with nepafenac had no corneal complications, but in patients with ICE who have malfunctioning endothelial cells, we have to be very careful about use of NSAIDs.