SD-OCT may help diagnose primary vitreoretinal lymphoma

Hyper-reflective subretinal infiltrates visible on spectral domain optical coherence tomography (SD-OCT) could help diagnose primary vitreoretinal lymphoma (PVRL), researchers believe.

The finding could lead to earlier diagnosis of the rare disease; wrote Dr Robert J. Barry from the University of Birmingham, Birmingham, UK, and colleagues in the British Journal of Ophthalmology. “It is hoped that increased awareness of characteristic OCT findings in PVRL may improve patient outcomes in this life-limiting disease,” they said.

Most often an extranodal presentation of non-Hodgkin's lymphoma, PVRL can be hard to diagnose. It only turns up in 0.01% of all ocular diagnoses, so many clinicians do not even think of it. And the clinical findings are non-specific; it can look like some other form of posterior or intermediate uveitis.

Its characteristic features, large non-clumped vitreous cells and yellow subretinal deposits associated with retinal pigment epithelium detachments, can be found in a lot of other diseases.

Clinical clues include vitreous cells in sheets, visual acuity better than predicted from the amount of uveitic involvement and lack of cystoid macular oedema. However, confirmation usually requires vitreoretinal biopsy, and even then 30% to 40% of cytology specimens generate false negative results. Immunological analyses only work with highly differentiated tumours and may be limited by the development of a T-lymphocyte-driven inflammatory response to tumour antigens.

Hyper-reflective lesion findings

SD-OCT has appeared successful as a non-invasive aid to diagnosis in previous very small case series. To further this research, Dr Barry and colleagues analysed records of 32 eyes of 22 patients from Moorfields Eye Hospital in London, UK, whose PVRL was later confirmed by biopsy.

Dr Barry and another masked observer assessed anonymised OCT images, compiling a list of positive findings. They used the earliest-available images, created prior to any lymphoma-specific treatment. They discussed these findings with the four other co-authors of the study to create a final list of features associated with PVRL.

They observed hyper-reflective lesions across multiple retinal layers. In 17 eyes, they found these lesions in the subretinal space, either in the form of discrete nodules or a confluent band.

These lesions were accompanied by disruption of the photoreceptor inner segment/outer segment junction. They found hyper-reflective infiltration in the inner layers of the retina in six eyes and irregularity of the retinal pigment epithelium in five eyes.

In five eyes, there were hyper-reflective foci in the posterior vitreous. In three, there were subretinal pigment epithelial deposits associated with steep elevation of the retinal pigment epithelium. There was cystoid macular oedema in five eyes.

The sub-retinal pigment epithelium infiltrates observed in these patients differed from choroidal infiltrates seen in choroidal lymphoma, the researchers said. In PVRL, the infiltration is localised between the retinal pigment epithelium and Bruch’s membrane. The choroid appears separately to the retinal pigment epithelium and immediately deep to Bruch’s membrane. The infiltration shows a homogenous, hyper-reflective quality.

By contrast, in choroidal lymphoma, the infiltration is usually of a mucosa-associated lymphoid tissue seen deep to Bruch’s membrane, without separation of the retinal pigment epithelium.

Recommendations

The researchers recommend prompt referral of patients with such findings to specialised uveitis services, and early consideration of oncology review. Early diagnosis of ocular lesions prior to the development of central nervous system disease can prolong life, they explained.

In addition to SD-OCT, fluorescein and indocyanine green angiography could also contribute to the diagnosis of PVRL, they suggested, adding that such tests have a positive predictive value of 89% and a negative predictive value of 85%.

On fluorescein angiography, punctuate hyperfluorescent window defects, round hypofluorescent lesions, masking and granularity can suggest PVRL. On indocyanine green angiography, small hypofluerescent lesions in the early phase become less apparent in the late frames.

Infiltration due to PVRL often improves with steroid therapy, leading to diagnostic confusion, they noted, so steroid therapy should halt for 2 weeks before a biopsy.

The researchers speculated that the OCT features they identified represent infiltrating lymphoma cells at various levels in the retina. Larger studies are needed to confirm whether the features identified are truly specific to PVRL, they concluded.