A comprehensive overview of diagnosis, imaging and treatment of vitreoretinal lymphoma

Abstract

Vitreoretinal lymphoma (VRL) is a rare B-cell intraocular neoplasia characterized by poor long-term prognosis and lack of effective therapies. It mainly involves the vitreous humor, the retina, and the retinal pigment epithelium (RPE), although anterior segment involvement can occur. VRL is classified as a lymphoma of immune privileged sites, along with testis lymphoma and primary central nervous system lymphoma (PCNSL). VRL and PCNSL are strictly connected indeed: 80% of VRL develop PCNSL, while 20% of patients with PCNSL present VRL during natural history of lymphoma. Due to the lack of worldwide consensus about diagnosis, therapy, and follow-up timing, VRL represents one of the most challenging ocular affections.VRL commonly masquerades as a posterior uveitis, and misdiagnosis often occurs because of partial response to topical steroids. Gold standard for diagnosis is cytological analysis of vitreous humor. However, this technique lacks sensitivity and supplemental molecular analyses can improve the diagnostic process. Multimodal imaging allows ophthalmologists to empower their clinical suspicion and a comprehensive examination can highlight typical features of VRL and justify further invasive procedures.There is no consensus about VRL therapy, and none of the therapeutical scheme has demonstrated to prevent cerebral involvement and improve patient's overall survival. Intravitreal injections of chemotherapeutics drugs, ocular radiation therapy and systemic chemotherapy can be considered in the treatment of VRL. Once cerebral involvement occurs, systemic chemotherapy must be included in the treatment as a life-saving therapy. Further multicentric studies are required to find out the best treatment of patients with VRL.

Keywords: MYD88; Vitreoretinal lymphoma; diagnostic vitrectomy; intravitreal chemotherapy; multimodal imaging; primary central nervous system lymphoma; uveitis.

Figure 1.

Multicolor fundus photography of a biopsy-proven VRL. Yellowish diffuse and irregular infiltrates can be disclosed at posterior pole.

Figure 2.

Ultra-widefield Fundus autofluorescence of two biopsy-proven VRL (a and b). Granular and mottled changes of alternating hyper- and hypo-autofluorescence can be disclosed in the retinal temporal mid-periphery (a) and at posterior pole (b). A leopard skin like appearance can be observed (b).

Figure 3.

B-scan Optical coherence tomography (OCT) of three biopsy-proven VRL. Retinal pigment epithelium (RPE) thickening and mottling can be disclosed, as well as small sub-RPE deposits (a, b and c, red asterisks). A small macular subretinal hypo-reflective deposit is marked in A (yellow asterisk). Vertical hyper-reflective spots are signs of intraretinal lymphomatous infiltration and have been highlighted in C (yellow arrows).

Figure 4.

Late phase fluorescein angiography of a biopsy-proven VRL. Diffused alternating areas of hyper- and hypo-fluorescence can be observed, with a leopard spot appearance.