Aqueous fluid sequencing shows promise for diagnosing intraocular lymphoma

Primary intraocular lymphoma is a great masquerader and can be mistaken for uveitis, often delaying diagnosis. In this study, the authors explored whether metagenomic deep sequencing (MDS) of ocular fluid could replace biopsy as a diagnostic test for primary intraocular lymphoma.

Study design

Aqueous fluid samples from 2 patients—one with vitreal lymphoma and another with intraocular B-cell lymphoma—were sent for MDS. The high-throughput sequencing approach can detect pathogens as well as common and rare cancer mutations.

Outcomes 

The first patient was HIV positive. Sequencing detected the presence of Epstein-Barr virus (HHV-4/EBV) and human herpes virus 8 (HHV-8) RNA, both implicated in a type of HIV-related lymphoma. Vitrectomy in this case was suggestive of lymphoma.

In the second patient, a rare mutation was found in the MYD88 gene—an uncommon mutation associated with B-cell lymphoma. Vitrectomy, performed 1 year prior, was negative for lymphoma. Histopathology of the anterior chamber tap, however, showed lymphoma cells.

Limitations

These were only 2 cases in this proof-of-concept study. Further testing in infectious and noninfectious uveitis and lymphoma cases is necessary to assess whether diagnostic biopsy can be replaced by this technique.

Clinical significance

The findings presented here demonstrate that MDS can accurately detect pathogen-related causes of inflammation that drive intraocular lymphomas, as well as common and rare cancer-associated mutations, in just 20 to 50 µL of aqueous fluid.

If shown reliable, this technique could potentially improve detection rates and permit earlier management of intraocular lymphomas. Aqueous samples could easily be obtained in the clinic from patients with suspected lymphoma.