An Off-Label Application of Anti-VEGF in Refractory Posttraumatic Irvine-Gass Syndrome: A Case Report

Background

Following intraocular surgery, Irvine-Gass syndrome (IGS) is the most common cause of unexpected visual diminution and is caused by cystoid macular oedema (CME) [1]. Probably due to its largely unknown aetiology, it causes a major therapeutic challenge.

The exact pathophysiology of CME in IGS remains unclear. The main hypotheses are based on acute intraocular inflammation and associated release of various chemical inflammatory mediators (prostaglandins, cytokines, endotoxin, and immune complex) during cataract surgery [1], [2]. Via activation of vascular endothelial growth factor (VEGF), as an angiogenic inducer, this leads to increased vascular permeability of the perifoveal capillaries [3].

By increasing phosphorylation of the tight junction proteins, the blood-retina barrier breaks down, thereby contributing to the development of intraretinal macular oedema [4]. Recent studies on patients with macular oedema confirmed elevated levels of VEGF and interleukin-6 in ocular fluids [1], [2]. The retina is initially resistant to the effect of local inflammatory mediators until prolonged exposure when increased vascular permeability of the perifoveal retinal capillaries occurs and CME manifests [1], [5]. All the discussed mechanisms represent the basis of the use of anti-VEGFs for the treatment of CME. Their safety has been tested in clinical trials [6].

Apart from the approved on-label application of ranibizumab and aflibercept in exudative age-related macular degeneration [7], macular oedema following retinal vein occlusion and diabetic macular oedema, an off-label anti-VEGF therapy with bevacizumab, can be as effective as steroids in exudative diseases. Due to its antioxidative effect, but also the decrease of choroidal vascular hyperpermeability and improvement of retinal pigment epithelium integrity, intravitreal injection of bevacizumab showed a benefit in the treatment of persistent serous retinal detachment in patients with Vogt-Koyanagi-Harada syndrome [8]. Despite the proven efficacy of bevacizumab in systemic use, it is still off-label in ophthalmology and therefore remains a controversial treatment option. Several studies, however, have shown its safety profile, particularly in terms of the absence of post-intervention inflammatory reactions [7], [9], [10], [11].

In 2009, the dexamethasone implant (Ozurdex, Allergan, Pharmaceuticals Inc., Westport, Ireland) was approved for the intravitreal treatment of CME in noninfectious posterior uveitis and branch or central retinal vein occlusion [12]. Based on the inflammation-triggered pathogenesis in diabetic macular oedema (DME), several studies were conducted to prove its efficacy. They demonstrated the effect of the dexamethasone implant particularly in DME patients with a specific inflammatory pattern, including hyperreflective patches and serous neuroretinal detachment [13]. During the COVID pandemic, in patients unable to maintain their anti-VEGF intravitreal, dexamethasone demonstrated a longer mechanism of action as well as anatomical and functional benefits [14].

For refractory IGS, the implantation of a dexamethasone depot is the primary on-label treatment. Corticosteroids target mediators in both the inflammatory and angiogenic cascades [15], restoring the blood-retinal barrier, as well as inducing Müller cell and RPE (retinal pigment epithelium) proliferation [16]. Intravitreal dexamethasone demonstrated improvement in patients with IGS, refractory to other treatments [17]. Its prolonged duration of action is of advantage in patients with IGS [18]. Cataract development and elevated intraocular pressure is a frequent complication of intravitreal dexamethasone and can be managed in most cases [19]. Nevertheless, in some patients with glaucoma or special anatomic situations, alternative treatment modalities should be considered.

In the case presented, we report the application of anti-VEGF therapy with bevacizumab (Avastin; Genentech und Roche, Basel, Switzerland) as a “first-line” treatment following unsuccessful topical therapy with prednisolone acetate 4 times daily and bromfenac eye drops once daily.

Publication History

Received: 28 September 2021

Accepted: 27 February 2022

Article published online:
26 April 2022

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