Although multiple indications exist for macular peeling, the most common include surgical correction for an epiretinal membrane (ERM; either primary or secondary) or macular hole (MH).¹ Reports describing the removal of preretinal proliferations began in the 1970s, with Machemer being the first to remove macular warping epiretinal membranes in the absence of other conditions.² Surgery is indicated for membrane removal in cases where vision is significantly impacted; however, in patients with increased disorganization of the retinal inner layers (DRIL), visual improvement after ERM removal may be limited.³ There is debate around the necessity of concurrently peeling the internal limiting membrane (ILM) when performing ERM surgery. Internal limiting membrane removal is recommended by some surgeons because the ILM may act as a scaffold for ERM recurrence, whereas others argue that ILM removal does not improve visual outcomes, recurrence of ERM is generally insignificant, and the long-term consequences of ILM peeling are unknown.^4,5 In MHs, ILM peeling, with the addition of ERM removal when present, is necessary to remove all tractional forces on the fovea. Typical surgery, consisting of a combination of pars plana vitrectomy, ILM peel, and gas tamponade, results in successful closure in more than 90% of MHs.^6-8

COMPLICATIONS

General complications may arise in the setting of a vitrectomy combined with a membrane peel, including, but not limited to, intraocular pressure fluctuations, cataract progression or pseudophakic lens dislocation, phototoxicity, retinal tears and/or detachment, retinal pigment epithelial changes, visual field defects, hypotony, vitreous hemorrhage, and endophthalmitis.^1,9,10 These are likely secondary to vitrectomy itself and not macular peeling and thus will not be the focus of this article. Complications more likely secondary to macular surgery, including retinal hemorrhages, retinoschisis and edema, paracentral scotomas and electroretinogram (ERG) changes, foveal displacement, eccentric macular holes, choroidal neovascular membranes, indocyanine green (ICG) toxicity, and dissociated optic nerve fiber layer (DONFL), will be discussed here.

RETINAL AND SUBRETINAL HEMORRHAGES

During the performance of the ILM peel, whitening of the underlying retina and small preretinal hemorrhages may appear. However, they do not lead to permanent damage.¹¹ Subretinal and vitreous hemorrhage have been reported during peeling, which might resolve spontaneously or with increased infusion pressure during vitrectomy.¹²

RETINOSCHISIS AND MACULAR EDEMA

Macular edema occurs, but often it occurs after cataract surgery, with the pattern of macular edema consistent with Irvine–Gass syndrome.^13,14 Retinoschisis has rarely been reported after membrane peeling with associated visual field defect.¹⁵

PARACENTRAL SCOTOMAS AND MULTIFOCAL ELECTRORETINOGRAPHY CHANGES

Paracentral scotomas can occur, even in patients with excellent surgical outcomes and visual acuity scores, and have been attributed to ILM removal or mechanical trauma to the nerve fiber layer.^13,16 In some patients, retinal edema seen in the postoperative period may be replaced by atrophy with corresponding visual field defects.¹⁵ It is hypothesized that removal of the ILM alters the architecture and function of the inner retina, and despite successful anatomic results, visual improvement may be limited, as demonstrated with multifocal electroretinography.¹⁷

FOVEAL DISPLACEMENT TOWARD THE OPTIC DISC

Both the peeling of ERM and ILM are linked to postoperative displacement of the fovea toward the optic disc. A clear explanation for this phenomenon has not been elucidated, but it may be secondary to releasing the increased traction on the temporal side of the fovea with an ILM peel, contractility changes within the retinal nerve fiber layer (RNFL) after peeling, or eccentric opening of the MH.^18-20

ECCENTRIC HOLES

First described by Rubinstein et al in 2005, iatrogenic extrafoveal full-thickness holes occur in less than 1% of cases and often develop within 1 week to 3 years following ILM peel.^21-23 The mechanism may be linked to trauma, ILM elevation, or a weakening of the retinal glial architecture.^1,22 These are often asymptomatic with no subretinal fluid; however, proximity to the fovea portends worse visual prognosis.^21,22 Optical coherence tomography may reveal flat, full-thickness holes.¹

RETINAL PIGMENT EPITHELIUM CHANGES AND CHOROIDAL NEOVASCULARIZATION

Iatrogenic punctate chorioretinopathy has been reported in the literature after ILM peeling without dye. Usually, these findings do not cause negative surgical outcomes.²⁴ Rarely, patients will develop choroidal neovascularization or retinal angiomatosis proliferation after ILM peeling, likely secondarily to trauma to the RPE and Bruch’s membrane, although some reports have documented a rate of up to 3%.^25,26

INDOCYANINE GREEN TOXICITY

Indocyanine green toxicity is a well-documented phenomenon, resulting in visual field defects (mainly of the nasal kind), reduced RNFL thickness, RPE changes, and, in late stage disease, optic nerve injury.^27,28 Steps should be taken to minimize toxicity, including appropriate ICG concentrations, limiting exposure to the retina, administering the dye in a fluid-filled eye, and protecting the subretinal space in a MH, because reports have shown atrophic RPE alterations at the site of the MH.²⁹ The mechanism is unknown, but it may be secondary to a directly toxic impact of ICG on the RPE or retina, or enhanced phototoxicity.³⁰

Chronically retained ICG can also pass along axons, and residual ICG may accumulate on the nerve fiber layer with resultant visual field defects.²⁸ Histologic studies have suggested that the use of ICG may also alter the cleavage plane of the inner retina, although this may also be secondary to the fluidics or infusion of vitrectomy.^1,31

DISSOCIATED OPTIC NERVE FIBER LAYER

Tadayoni et al were the first to describe DONFL, a condition characterized by a “moth-eaten” appearance. Initially it may present as a swelling of the arcuate RNFL, followed by arcuate striate within the posterior pole on infrared and autofluorescence imaging, or as dark spots on macular imaging with en-face OCT (Figure 1). These can cause thickness changes primarily within the RNFL, although a few studies have found variations within the ganglion cell layer as well.^32,33 These typically occur within 3 months of the macular peel in more than 50% of patients.^32,34

Spaide later noted that the characteristic dimples seen on en-face OCT are secondary to trauma to the RNFL, as part of the healing response, and are not caused by the dissociation of optic nerve fibers.³⁵ The pathophysiology of DONFL is not well understood, but it has been attributed to damage of the Müller cells and the inner retina, dye use, and/or to the temporal retinal thinning, secondary to traction.³⁴ These changes are not linked to overall visual acuity decline, but they may be associated with retinal sensitivity loss and scotomas, although this remains in dispute.^36-38

EPIMACULAR PROLIFERATIVE RESPONSE

Epimacular proliferation following ILM peel is rarely seen and is hypothesized to occur secondary to injury during the ILM peel, which stimulates glial proliferation.³⁹ In one study, postoperative ERM formation was noted in 5% of patients.¹¹

CONCLUSION

Generally, macular peeling is well tolerated with favorable anatomic and visual outcomes. Surgeons should be aware of potential complications during and after this procedure. RP

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