Case report: successful closure of a large macular hole secondary to uveitis using the inverted internal limiting membrane flap technique

To the best of our knowledge, this is the first report of the successful closure of a large MH secondary to uveitis using the inverted ILM flap technique. Hassan et al. reported a closure rate of 17 % for MHs secondary to uveitis after vitrectomy, ILM peeling, and gas or silicone tamponade [1], which was much lower than the rate for idiopathic MHs [2, 3]. They suggested that the reasons for this lower closure rate was the presence of damage to the retina and retinal pigment epithelium due to inflammation and the large diameter of the MHs [1]. In addition to these observations, our case presented with ERM formation, post-inflammatory chorioretinal atrophy, and retinal degeneration including the juxtafoveal region, which can cause adhesion of the retina and RPE in this area. The presence of these conditions in the eye led us to use the inverted ILM flap technique instead of conventional ILM peel in this patient.

Although we achieved a successful closure of the MH in this patient, long-term observation will be needed to check for excessive gliosis in the retina. Michalewska et al. hypothesized that the inverted ILM flap technique stimulates proliferation of glial cells that fill MHs, thereby enhancing closure and improving MH closure rates [4]. In the neural tissues of the central nervous system and the retina, activation of glial cells occurs in response to any form of injury or disease and can have both protective and detrimental effects [6]. Müller cells are the principal glial cells in the retina and play of crucial roles in supporting neuronal function [7]. At the early stage of tissue damage, gliosis is an important neuroprotective event that is thought to be a cellular attempt to limit the extent of tissue damage [7]. However, the persistent activation of glial cells may contribute to tissue damage, including endothelial dysfunction and angiogenesis [8]. In eyes with a history of uveitis, larger amount of inflammatory cytokines can be secreted in response to surgery than in normal eyes. In such cases, Müller cells may be activated, proliferate excessively along the inverted ILM flap, and may induce excessive gliosis in the retina. In our patient, however, we did not see any excessive gliosis, which appears as highly reflective material in OCT [9, 10], during the 7 month follow-up period.

Recently, Shin et al. have reported two modifications of the original inverted ILM technique [11]. The first modification was covering the MH with a single-layered ILM flap, which may provide a more physiological structure for glial proliferation and retinal regeneration. The second modification was keeping the inverted ILM flap in position during surgery by applying perfluoro-n-octane (PFO) over the macula. However, this modified technique required creating three flaps along MH in specific order, which ware removed to create the fourth flap to be used as cover flap, which seemed technically complicated and difficult.

In addition, it took several minutes for the PFO to evaporate completely at the end of the fluid-air exchange, while continuously removing fluid from the disc. In this study, we modified their procedure for creating a single-layered ILM flap and keeping the flap in position. First, we peeled off the ILM in a circular fashion, leaving it attached at the edge of the MH, and then trimmed half of the peeled ILM with a vitreous cutter to create a single-layered ILM flap. Second, we used low molecular weight hyaluronic acid to stabilize the inverted ILM flap and left this in place at the end of the surgery. These modifications enable us to make a single-layered ILM flap and stabilize it more easily than in the previous methods described.

We initially used CBBG to stain the ILM and then re-stained it with 0.25 % ICG. Imai et al. reported that an expansion of RPE atrophy occurred 1 week after inverted ILM flap technique using ICG staining [12]. They assumed that the ICG-stained ILM flap provoked the RPE damage. In our patient, however, we have observed no expansion of the pre-existing chorioretinal atrophy up to 6 months after surgery. Further observations will be required to assess the safety of using ICG staining in the inverted ILM flap technique.

In conclusion, our case report suggests that the inverted ILM flap technique may be beneficial for the treatment of large MHs, secondary to uveitis. To determine the actual efficacy of this technique, further prospective studies involving a larger number of patients will be required.