Crunch Syndrome

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Article initiated by:

Amr K. Hassan

All contributors:

Leo A. Kim, MD, PhD, Oscar Chen, Amr K. Hassan

Assigned editor:

Durga Borkar, MD, MMCi

Review:

Assigned status Update Pending

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Disease Entity

Anti-Vascular Endothelial Growth Factor (VEGF) Crunch Syndrome is the progression to tractional retinal detachment (RD) following intravitreal anti-VEGF injections in eyes with proliferative diabetic retinopathy (PDR) .

Etiology

Available anti-VEGF agents include bevacizumab, pegaptanib, ranibizumab, and aflibercept. Despite promising efficacy in reducing vision loss in PDR, there have been several reports of serious adverse events associated with anti-VEGF therapy, including the development or progression of retinal detachment characterized as “crunch syndrome” .

Its incidence has been reported to be between 1.5%:18.4%. The incidence is higher in patients with severe PDR and preexisting RD .

Risk Factors

It occurs 1:6 weeks after intravitreal anti-VEGF injection, with a mean duration till onset of 13 days. The most commonly responsible Anti-VEGF agent is Bevacizumab . Risk factors include:

• Increased number of anti-VEGF injections.
• Increased severity of Diabetic Retinopathy.
• Associated fibrosis.
• Preexisting RD .
• patients with extensive areas of ischemia and severe fibrovascular proliferation .

Randomized controlled trials investigating the efficacy of ranibizumab compared with PRP did not report anti-VEGF crunch as an adverse event following treatment . There is currently no publication linking intravitreal aflibercept with anti-VEGF crunch for the treatment of PDR.

The incidence of Combined Tractional and Rhegmatogenous RD is quite low (0.05%:0.5%) , however, the risk increases when a ring-shaped fibrovascular membrane is present, up to 43% .

General Pathology

The resulting retinal detachment develops from contraction of vitreoretinal adhesions produced by extensive areas of angiogenesis and dense fibrous proliferation . The natural history of PDR is characterized by angiogenesis due to VEGF upregulation, vascular growth into the attached posterior hyaloid, fibrous tissue formation that accompanies neovascularization, and eventual contraction of fibrous tissue that results in tractional retinal detachment .

The pathogenesis of PDR implies that most PDR eyes will progress from angiogenesis dominance to fibrosis dominance over time. It has been postulated that an anti-VEGF drug is likely to accelerate the progression .

Diagnosis

History

Anti-VEGF crunch typically manifests as sudden vision loss between 1 and 6 weeks following intravitreal anti-VEGF injection . When injections are administered in patients with severe PDR refractory to PRP, the mean time to development or progression of crunch syndrome is 13 days, with a range of 3 to 31 days.

Signs

Fundus examination may reveal vitreous hemorrhage, regression of neovascular tissue, fibrovascular proliferation, scar tissue formation, shrinkage of neovascular membrane and TRD .

Differential Diagnosis

Crunch Syndrome may occur following Retinopathy of Prematurity , Eales disease , familial exudative vitreoretinopathy , and Coats disease .

Management

Patients with anti-VEGF crunch may be treated with vitrectomy, membranectomy, photocoagulation, and extended intraocular tamponade .

References

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