Purpose

The aim of this study was to briefly review the clinical and diagnostic features of vitreoretinal lymphoma (VRL) and to introduce the recent introduction of metagenomic deep sequencing in this ocular lymphomatous disease.

Design and methods

Review and description of the process of using metagenomic deep sequencing for ocular specimens at the Proctor Foundation, University of California, San Francisco, CA.

Results

VRL masquerades as a uveitis, but clinical signs of subretinal lesions, and vitritis should prompt the inclusion of VRL in a differential diagnosis. Imaging features such as hyporeflective infiltrative lesions between the retinal pigment epithelium and Bruch's membrane are compatible with VRL, but diagnosis requires satisfying specific cytopathological and immunohistochemical or molecular features. Diagnosis, then, is subject to the cellularity, viability, and volume of the specimen submitted for these tests. Metagenomic deep sequencing has the ability to detect numerous lymphoma-associated mutations and is able to utilize minute volume samples and cell-free nucleic acid, so is well-suited for ocular tissues.

Conclusions

Metagenomic deep sequencing may offer an additional tool in the future with which to diagnose VRL.

Purpose

To identify peripheral blood transcriptome differences in uveitis patients with sarcoidosis compared to those with Vogt-Koyanagi-Harada (VKH) syndrome and controls.

Methods

Ten patients with uveitis compatible with sarcoidosis (eight with pulmonary sarcoidosis, one with central nervous system sarcoidosis, and one with conjunctival sarcoidosis), nine patients with VKH, and nine healthy controls were prospectively enrolled.

Results

Ten genes exhibited a four-fold difference in expression in sarcoidosis patients compared to controls, many being involved in regulating inflammatory processes or cellular responses to microbes.

Conclusions

This research suggests that the transcriptome in sarcoidosis is robust enough to be detected in the peripheral blood and that sarcoidosis can be distinguished from healthy controls. Differentially expressed genes may serve as candidates warranting further investigation with respect to disease pathophysiology and may provide additional information, such as ability to stratify patients based on associated disease severity and anatomical location of inflammation within the eye.

Purpose

The purposes of this study were to assess the reproducibility of a novel standardized technique for capturing corneal subbasal nerve plexus images with in vivo corneal confocal microscopy and to compare nerve metrics captured with this method in participants with dry eye and control participants.

Methods

Cases and controls were recruited based on their International Statistical Classification of Diseases and Related Health Problems (ICD-10) diagnoses. Participants completed the following 3 ocular symptom questionnaires: the Ocular Surface Disease Index, Neuropathic Pain Symptom Inventory, and Dry Eye Questionnaire 5. A novel eye fixation-grid system was used to capture 30 standardized confocal microscopy images of the central cornea. Each participant was imaged twice by different operators. Seven quantitative nerve metrics were analyzed using automated software (ACCmetrics, Manchester, United Kingdom) for all 30 images and a 6-image subset.

Results

Forty-seven participants were recruited (25 classified as dry eye and 22 controls). The most reproducible nerve metrics were corneal nerve fiber length [intraclass correlation (ICC) = 0.86], corneal nerve fiber area (ICC = 0.86), and fractal dimension (ICC = 0.90). Although differences were not statistically significant, all mean nerve metrics were lower in those with dry eye compared with controls. Questionnaire scores did not significantly correlate with nerve metrics. Reproducibility of nerve metrics was similar when comparing the entire 30-image montage to a central 6-image subset.

Conclusions

A standardized confocal imaging technique coupled with quantitative assessment of corneal nerves produced reproducible corneal nerve metrics even with different operators. No statistically significant differences in in vivo corneal confocal microscopy nerve metrics were observed between participants with dry eye and control participants.

Introduction

Cytomegalovirus (CMV) anterior uveitis is a recognised cause of anterior uveitis in immunocompetent patients and is preventable cause of vision loss. Ocular sequelae include corneal endothelial damage which can cause corneal oedema and failure, as well as glaucoma. Recurrences of inflammation are common and therefore patients are often exposed to long-term therapy. Oral therapy is available in the form of valganciclovir, although with the caveat of systemic side effects such as bone marrow suppression and renal failure necessitating regular interval laboratory monitoring. Recent reports have demonstrated that topical 2% ganciclovir solution may offer promising treatment outcomes in patients with CMV anterior uveitis with superior safety, cost-effectiveness and convenience profiles. An investigation into the relative equipoise of these therapies is warranted for these reasons.

Methods and analysis

The Systemic and Topical Control of Cytomegalovirus Anterior uveitis: Treatment Outcomes (STACCATO) trial is designed as a multicentre, block randomised by site, double-masked, placebo-controlled trial comparing the efficacy of oral valganciclovir, 2% topical ganciclovir and placebo in treating PCR-proven CMV anterior uveitis. Participant clinical evaluation will occur at three study time points by a masked study ophthalmologist over a 28-day period to assess resolution of ocular inflammation (secondary outcome). A control group will provide additional information about the possible impact that the infected host's immune response may play in controlling local viral replication. The primary analysis is an analysis of covariance (three arms) correcting for baseline to compare quantitative CMV viral load in the anterior chamber (AC) aqueous fluid before and 7 days after treatment.

Ethics and dissemination

The University of California San Francisco Committee on Human Research and the Khon Kaen University Institutional Review Board have given ethical approval. The results of this trial will be presented at local and international meetings and submitted for peer-reviewed journals for publication.

Trial registration number

NCT03576898.