Peripheral Blood Transcriptome in Patients with Sarcoidosis-Associated Uveitis.

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.

High Resolution DNA Typing of Human Leukocyte Antigen A29 in Familial Birdshot Chorioretinopathy.

Purpose: To describe high-resolution DNA typing of HLA-A29 in patients with familial birdshot chorioretinopathy (BSCR).Methods: A retrospective clinical chart review was performed of all patients at the Francis I. Proctor Foundation with BSCR with a documented family history of HLA-A29 positive BSCR. High-resolution HLA-A29 typing was performed for these patients.Results: Two families with familial BSCR were identified. Family 1 consisted of a mother, daughter and maternal aunt with BSCR. All were positive for the HLA-A29*02 allele. Family 2 consisted of two sisters with BSCR who were both positive for the HLA-A29*02 allele.Conclusions: Familial BSCR is rare and we report the high-resolution DNA typing of HLA-A29 in two families with familial BSCR and their associated clinical outcomes, including the first documented case of multigenerational BSCR.

Validation of a Novel Confocal Microscopy Imaging Protocol With Assessment of Reproducibility and Comparison of Nerve Metrics in Dry Eye Disease Compared With Controls.

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.

Treatment of Cytomegalovirus Anterior Uveitis at a North American Tertiary Center With Oral Valganciclovir.

PURPOSE: Cytomegalovirus is an increasingly recognized cause of anterior uveitis. We present clinical features of cytomegalovirus anterior uveitis (CMVAU) and outcomes of oral valganciclovir treatment at a tertiary referral center in North America. METHODS: This is a retrospective case series review (2002-2014) of immunocompetent patients with CMVAU treated with valganciclovir 900 mg BID and subsequent maintenance dosing of ≤450 mg BID. Most patients were prescribed topical corticosteroids concurrently. Diagnostic evaluations and clinical features at baseline and follow-up were reviewed. Resolution time, maintenance of quiescence, and adverse events were assessed. RESULTS: Eighteen eyes of 16 patients were included. The mean age of diagnosis was 41 years. At diagnosis, mean best-corrected visual acuity was 0.30 LogMAR and mean intraocular pressure (IOP) was 18.4 mm Hg; 14 eyes (78%) had an active anterior chamber (AC) cell, 8 (44%) had circinate keratic precipitates, and 6 (33%) had iris atrophy. The mean follow-up duration was 48 months. Fourteen eyes of 12 patients were available for the 12-month follow-up; patients demonstrated improvement in best-corrected visual acuity (difference: -0.21 LogMAR, 95% CI -0.33 to -0.09; P = 0.003), AC cell (OR = 0.10, 95% CI 0.02-0.41; P = 0.002), and IOP (difference: -4.21 mm Hg, 95% CI -7.98 to -0.44; P = 0.03) compared with baseline. One patient experienced a serious adverse event likely due to valganciclovir. Thirteen eyes experienced recurrence of inflammation: 7 (54%) on prophylactic dose of valganciclovir and 6 (46%) after stopping. CONCLUSIONS: Valganciclovir appears effective and safe for treating CMVAU in this retrospective case series. Long-term antiviral prophylaxis does not abolish recurrences, although it may possibly reduce their frequency when compared with no prophylaxis.

IgA Nephropathy-Associated Uveitis: A Case Presentation.

Purpose: To describe a case of bilateral panuveitis in the setting of IgA nephropathy. Methods: Retrospective review of clinical records, fundus, and optical coherence tomographic (OCT) images, and fluorescein angiography. Results: A 36-year-old female presented with IgA nephropathy and contemporaneous ocular manifestations of one-year duration. Clinical exam demonstrated bilateral panuveitis, 3+ anterior chamber (AC) cell in the right eye (OD), and 0.5+ AC cell in the left eye (OS). Funduscopic exam demonstrated diffuse yellow drusenoid deposits bilaterally (OU), accentuated on fundus autofluorescence as focal areas of hyperautofluorescence. Deposits correlated with retinal pigment epithelium hyper-reflectivity on OCT, and choroidal hypo-fluorescence on fluorescein angiography. The patient was managed with oral prednisone. Conclusion: IgA nephropathy is a systemic autoimmune disease that may be associated with uveitis. Immunosuppression with corticosteroids appears to be an effective therapy.

A double masked randomised 4-week, placebo-controlled study in the USA, Thailand and Taiwan to compare the efficacy of oral valganciclovir and topical 2% ganciclovir in the treatment of cytomegalovirus anterior uveitis: study protocol.

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.

Primary vitreoretinal lymphoma: empowering our clinical suspicion.

PURPOSE OF REVIEW: Vitreoretinal lymphoma (VRL) is well known as a masquerade syndrome. However, delays in diagnosis are common particularly because of the small volume of tissue that is used for investigative studies. We outline the current diagnostic tests available to clinicians and provide a glimpse of possible future novel diagnostics. RECENT FINDINGS: The use of spectral domain ocular coherence tomography to identify subretinal lesions has proven to be a reliable ally to clinicians. Nevertheless, the diagnostic gold standard remains cytology, which requires a skilled pathologist. Molecular tests, including MYD88 polymerase chain reaction testing has further refined our diagnostic capabilities. Metagenomic deep sequencing is a newer molecular test that offers the ability to identify any mutation associated with lymphoma development and may offer more sensitive testing in the future. SUMMARY: Clinicians have developed a strong acumen for suspecting VRL based upon clinical features, which can further be supported by a variety of imaging modalities. Delays in diagnosis continue to occur particularly because of the small volume of ocular fluid available for testing and because current tests offer a biased approach in terms of limited scope of detecting a specific mutation or cytopathologic feature(s). Newer molecular techniques feature an expanded scope of detecting any mutation associated with lymphomatous development.