Update on ocular tuberculosis.

PURPOSE OF REVIEW: Despite recent downtrends, tuberculosis remains a worldwide public health concern. This review provides an update on recent demographic data, clinical and experimental data, and diagnostic modalities. RECENT FINDINGS: Quantitative PCR showing mycobacterial load in intraocular fluids may have an emerging role in the diagnosis of ocular tuberculosis when used in combination with ophthalmic features of tuberculosis. Recent investigations in porcine models of ocular tuberculosis have provided valuable insight into the microbiologic, histologic, and clinical features of Mycobacterium tuberculosis infection of the choroid. Differentiating features between sarcoidosis and tuberculosis include tuberculin skin test status, the presence of ocular surface disease, and the anatomic relationship between vasculitis and choroiditis. SUMMARY: The diagnosis of presumed ocular tuberculosis remains a clinical challenge with currently available diagnostic modalities. Although newer interferon-γ release assays can distinguish exposure to M. tuberculosis from the Bacille-Calmette-Guérin vaccine strain, they currently lack the specificity to distinguish between latent tuberculosis infection and active tuberculosis. Continued improvement in the currently available molecular diagnostic techniques including quantitative PCR may be valuable in our ability to establish an earlier etiologic diagnosis and institute appropriate antimycobacterial therapy.

Phenotypic and Genetic Spectrum of Autosomal Recessive Bestrophinopathy and Best Vitelliform Macular Dystrophy.

Purpose: Autosomal recessive bestrophinopathy (ARB) and vitelliform macular dystrophy (VMD) are distinct phenotypes, typically inherited through recessive and dominant patterns, respectively. Recessively inherited VMD (arVMD) has been reported, suggesting that dominant and recessive BEST1-related retinopathies represent a single disease spectrum. This study compares adVMD, arVMD, and ARB to determine whether a continuum exists and to define clinical and genetic features to aid diagnosis and management. Methods: One arVMD patient and nine ARB patients underwent standard ophthalmic examination, imaging, electrophysiology, and genetic assessments. A meta-analysis of reported BEST1 variants was compiled, and clinical parameters were analyzed with regard to inheritance and phenotype. Results: Among 10 patients with biallelic BEST1 variants, three novel ARB variants (p.Asp118Ala, p.Leu224Gln, p.Val273del) were discovered. A patient with homozygous p.Glu35Lys was clinically unique, presenting with VMD, including hyperautofluorescence extending beyond the macula, peripheral punctate lesions, and shortened axial-length. A tritan-axis color vision deficit was seen in three of six (50%) of ARB patients. Attempts to distinguish recessively-inherited ARB and dominantly-inherited VMD genotypically, by variant frequency and residue location, did not yield significant differences. Literature meta-analysis with principle component analysis of clinical features demonstrated a spectrum of disease with arVMD falling between adVMD and ARB. Conclusions: This study suggests that arVMD is part of a continuum of autosomal recessive and dominant BEST1-related retinopathies. Detailed clinical and molecular assessments of this cohort and the literature are corroborated by unsupervised analysis, highlighting the overlapping heterogeneity among BEST1-associated clinical diagnoses. Tritan-axis color vision deficit is a previously unreported finding associated with ARB.

Fundus autofluorescence changes in cytomegalovirus retinitis.

PURPOSE: The purpose of this study was to describe fundus autofluorescence imaging features of cytomegalovirus (CMV) retinitis and to correlate fundus autofluorescence features with clinical activity. METHODS: A retrospective case series was undertaken to evaluate nine eyes of six patients with active CMV retinitis. Patients were evaluated with a comprehensive ophthalmic examination, fundus autofluorescence imaging, and fundus photography. Oral valganciclovir, intravitreal ganciclovir, intravitreal foscarnet, or an ganciclovir implant was administered as clinically indicated. RESULTS: In all nine eyes with active CMV retinitis, a hyperautofluorescent signal on fundus autofluorescence imaging was correlated spatially with the border of advancing CMV retinitis. Stippled areas of alternating hyperautofluorescence and hypoautofluorescence were observed in regions of retinal pigment epithelium atrophy from prior CMV retinitis. In three eyes with subtle CMV reactivation, a hyperautofluorescent border was helpful in the detection and localization of active CMV retinitis. In another patient, diffuse, punctate hyperautofluorescence after intravitreal ganciclovir and foscarnet was a concern for medication-related toxicity. CONCLUSION: Fundus autofluorescence imaging was valuable in highlighting areas of active CMV retinitis in all patients in this series, including two patients with subtle clinical features. Fundus autofluorescence may be useful as an adjunctive imaging modality for the detection of CMV activity and aid in our understanding of the structural changes during episodes of CMV retinitis.

A double-masked, randomized study to investigate the safety and efficacy of daclizumab to treat the ocular complications related to Behçet's disease.

PURPOSE: To investigate the safety and efficacy of daclizumab (Zenapax, humanized anti-Tac, HAT) in controlling the ocular manifestations of Behçet's disease. DESIGN: Randomized, placebo-controlled, double-masked clinical trial. PARTICIPANTS: Seventeen participants with Behçet's disease experiencing at least two prior ocular attacks and requiring treatment with immunosuppressive agents for the ocular complications of Behçet's disease. METHODS: Participants received either intravenous placebo or daclizumab (1 mg/kg) infusions every two weeks for six weeks, then every four weeks while continuing their standard immunosuppressive regimens. If clinically indicated, tapering of the standard immunosuppressive medications was allowed after six months of study enrollment. Complete ocular and physical examinations and an adverse event assessment were performed at baseline and prior to each study infusion. MAIN OUTCOME MEASURES: Primary safety endpoints were the development of a life-threatening complication or a severe opportunistic infection. Primary efficacy outcomes were the number of ocular attacks and an assessment of systemic immunosuppressive medications required during the study, including the ability to taper concomitant immunosuppressive therapy. RESULTS: Nine participants randomized to daclizumab and eight to placebo were followed monthly. Follow-up ranged from one to 34 months, with a median follow-up of 15 months. Two participants randomized to daclizumab discontinued study therapy prior to the end of the study for personal reasons. No participant experienced a safety endpoint, and visual acuity remained stable in all participants during the course of the study. Ten participants (six daclizumab, four placebo) experienced ocular attacks requiring therapy. The median ocular attack rate during the study was greater in the daclizumab arm than the placebo arm (median 1.27 vs. 0.17 attacks/year, respectively). Participants in the placebo arm also experienced a greater reduction in the immunosuppressive medication score compared to participants receiving daclizumab (median -4.0 vs. -1.0, respectively). CONCLUSIONS: The observed results in the placebo group demonstrate that careful follow-up and treatment with standard combination immunosuppressive therapy can be effective for the management of the ocular complications of Behçet's disease. In our small study, there was no suggestion that daclizumab was beneficial in comparison with placebo. However, the low observed attack rate limited our ability to make a definitive treatment group comparison.