Commentary: Treatment of postoperative cystoid macular edema in vitrectomized eyes: An enigma.

Abstract

Post-operative cystoid macular edema (PCME) is a sight-threatening complication that could affect visual recovery following a successful ocular surgery. Irvine–Gass syndrome, that is, PCME following cataract surgery has extensively been studied. The incidence of clinical CME following phacoemulsification ranges from 0.2% to 2.35%.[1] The incidence of PCME following vitrectomy for vitreous floaters, rhegmatogenous retinal detachment (RRD), and the epiretinal membrane (ERM) has been found to be around 5%, 10–25%, and 13–47%, respectively.[1-4] Although the exact pathophysiology of PCME remains debatable, the most probable cause seems to be subclinical low-grade inflammation. Studies have shown that the levels of cytokines and prostaglandins are elevated in such eyes, leading to blood–aqueous barrier breakdown and consequent fluid accumulation.[1-4] Pole et al.[2] described the optical coherence tomography (OCT) characteristics of PCME after RRD surgery. These included fovea-involving diffuse CME, which involved all four macular quadrants and cysts in the inner nuclear and outer plexiform layers. In untreated eyes, the cysts may coalesce into larger irregular, polygonal-shaped cavities. CME may resolve spontaneously but cause disorganization and atrophy of the retinal layers. Several risk factors for the development of PCME following vitrectomy have been identified. Risk factors following RRD surgery include old age, cataract surgery, macula-off RRD, longer duration, pre-existing proliferative vitreoretinopathy changes (C or higher), intra-operative retinectomy, and multiple surgeries.[12] Risk factors following ERM removal surgery include old age, cataract surgery, stage 4 ERM, and the presence of pre-existing intraretinal cysts.[34] The post-operative tamponading agent did not influence the development of PCME in either pathology.[1-4] To date, there has been no consensus on the treatment for PCME. Its management is often complex due to its recurring nature. The various available treatment options include topical steroid and non-steroidal anti-inflammatory drug (NSAID) drops; intravitreal anti-vascular endothelial growth factor (VEGF) and triamcinolone acetonide (TA) injections; intravitreal dexamethasone and fluocinolone implants; suprachoroidal triamcinolone injection; and posterior subtenon and trans-tenon retrobulbar triamcinolone injection. The efficacy of topical treatment in previously vitrectomized eyes is usually limited.[12] Similarly, anti-VEGF injections also tend to be less effective in vitrectomized eyes due to faster clearance and reduced half-life.[12] Intravitreal triamcinolone acetonide (IVTA) injection has been found to be better than anti-VEGF injections in improving macular thickness and visual acuity.[2] However, the mean elimination half-life in vitrectomized eyes is merely 3.2 days compared to 18.6 days in non-vitrectomized eyes.[5] On the contrary, the vitreoretinal pharmacokinetic profiles of dexamethasone and fluocinolone implants in vitrectomized eyes are similar to that in non-vitrectomized eyes. Intravitreal dexamethasone implant has been found to be an effective treatment option for eyes with PCME following vitrectomy for RRD and even endophthalmitis.[67] Eyes that underwent vitrectomy for ERM compared to RRD, presence of subretinal fluid, intact outer retinal layers, and worse baseline best-corrected visual acuity (BCVA) have higher chances of visual improvement. Owing to the recurrent nature of the disease, multiple injections are often needed.[6] Intravitreal fluocinolone acetonide implant has been shown to achieve persistent functional and anatomical improvement with long recurrence-free periods. Miguel–Escuder et al.[8] suggested that it could be considered as a therapeutical option in eyes with refractory PCME following vitrectomy. Suprachoroidal TA injection with the help of custom-made needles is another treatment option. Due to its unique position, the suprachoroidal space serves as a drug reservoir with slow drug washout and better absorption. Animal model-based pharmacokinetic studies have shown that a 12-fold higher drug concentration can be achieved in the retina along with reduced entry drug in the anterior chamber, thus reducing the risk of intraocular pressure rise and cataract formation.[9] Trans-Tenon’s retrobulbar TA infusion has also been used successfully for the management of refractory diabetic macular edema (DME) in vitrectomized eyes. The described technique included making an incision in the conjunctiva and the Tenon’s capsule in the inferotemporal quadrant followed by infusion of 40 mg triamcinolone acetonide with a 25-gauge curved blunt cannula into sub-Tenon’s space under topical anesthesia.[10] Posterior subtenon triamcinolone (PST) injections have classically been used for the management of intermediate uveitis. It has been shown to provide a sustained high level of TA in the vitreous cavity level along with low systemic TA levels that cannot alter the systemic cortisol levels.[11] We congratulate the authors for their manuscript evaluating the efficacy and safety of PST for the treatment of chronic PCME in vitrectomized eyes.[12] However, prospective randomized studies with a larger sample size are required to compare the efficacy with other treatment modalities. Because simultaneous complicated cataract surgery is itself a risk factor for the development of PCME, eyes with nucleus drop should be excluded. Additionally, the management of a raised intraocular pressure in the steroid responder eyes may be challenging, because the depot of TA in the posterior subtenon location is difficult to remove completely.