Retinal Fibrosis after Intravitreal Injections:Part 3:the Crunch Syndrom by Gabriela Grimaldi and Giuseppe Cancian

The Crunch Syndrome is a complication associated after anti-VEGF injections in eyes with retinal ischemia and neovascularization. It is crucial to underscore the risks of anti-VEGF treatment in the presence of severe retinal ischemic diseases. Our case highlights the inclusion of BRVO among these conditions.

Retinal Fibrosis 3/3

Too few anti-VEGF treatments in the case of nAMD are associated with poorer long-term visual acuity: the more injections, the better the outcomes.
The risks of undertreatment are clearly emphasized in this article by Prof. Bandello, which I recommend.

What this article tells us:

Clinical trials of anti-VEGF agents and their extension studies demonstrated initial VA gains maintained at 4 years and beyond (up to 7 years) with continuous proactive treatment. Visual outcomes correlated with injection frequency. In real-world practice, patients are usually undertreated, accounting for the VA decline over time.

However, what we want to emphasize in this issue of the EON is the concept that even excessive treatment with anti-VEGF can drastically reduce VEGF levels, triggering an angio-fibrotic switch that releases profibrotic factors, leading to rapid onset of retinal fibrosis (see also Dr. Di Sandro’s lecture in Notebook #43). This phenomenon—well known and described in proliferative diabetic retinopathy (Crunch Syndrome, Tan Y, 2021)—is presented here for the first time in the literature in the context of treating a highly ischemic branch retinal vein occlusion (BRVO).

Literature:

Tan,Yran et al. “Anti-VEGF crunch syndrome in proliferative diabetic retinopatrhy: a review. Survey of ophthalmology 66.6 (2021): 926-932

Kuiper EJ et al:The Angio-Fibrotic Switch of VEGF and CTGF in Proliferative Diabetic Retinopathy. PLoS ONE 3(7): e2675. doi:10.1371/journal.pone.0002675

Our hypothesis is that the severity of ischemia plays an essential role as a biomarker in the onset of severe fibrosis in response to anti-VEGF injection.

We had previously summarized Giuseppe’s lecture for another presentation elsewhere—perhaps this abstract helps contextualize the lecture and serves as a common thread:

Crunch-Syndrome after BRVO: nefarious effects of the anti-VEGF treatment

Abstract

Purpose: This speech presents the first description in the literature of Anti-VEGF-Crunch Syndrome in a case of Branch Retinal Vein Occlusion (BRVO) with a sequential analysis of macular Optical Coherence Tomography (OCT) and wide-field fundus photography.

Observation: A 61-year-old patient with an extremely ischemic superior temporal BRVO underwent treatment with anti-VEGF on a pro re nata (PRN) basis to resolve secondary cystoid macular edema (CME) (Visual Acuity (VA): 0.6). The treatment successfully resolved the edema. Two years later, the edema recurred, and fundus autofluorescence (AF) revealed persistent severe retinal ischemia, two areas of neovascularization, and an onset of retinal fibrosis. The patient underwent four additional rounds of anti-VEGF treatment, resolving the neovascularization but rapidly worsening the significant supramacular fibrosis associated with traction and retinal schisis (VA 0.1).

Conclusions: In the state of extreme retinal ischemia, the second round of anti-VEGF treatment initially resolved macular edema but subsequently induced significant retinal fibrosis, likely due to an imbalance between Vascular Endothelial Growth Factor (VEGF) and Connective Tissue Growth Factor (CTGF). This imbalance resolved the neovascularization but induced fibrosis. Similar to the ischaemic retina in diabetic retinopathy and other pathologies, the administration of anti-VEGF in BRVO can induce a Crunch Syndrome with fibrosis. Vitrectomy prevents the extension of the pathology but does not improve visual acuity. The Crunch Syndrome is a complication associated with intravitreal anti-VEGF injections in ischaemic retinal conditions, most commonly described in proliferative diabetic retinopathy, but also in Eales and Coats disease. It involves rapid progression of retinal fibrosis after anti-VEGF injections in eyes with retinal ischemia and neovascularization.

Importance: It is crucial to underscore the risks of anti-VEGF treatment in the presence of severe retinal ischemic diseases. Our case highlights the inclusion of BRVO among these conditions.

But let us not delay any further. .

The presentation is delivered at a high scientific level but also with a lighthearted spirit by these two excellent colleagues of mine!