Optic Disc Edema Is an Under-Recognized Feature of Birdshot Chorioretinitis.

BACKGROUND: Optic disc edema is a feature of many ophthalmic and neurologic conditions. It remains an underappreciated feature of birdshot chorioretinitis (BSCR), leading to delay in diagnosis and treatment. The purpose of our study was to identify clinical features that are concomitant with optic disc edema and suggest a diagnosis of BSCR. METHODS: Retrospective multicenter case series of 29 patients who were referred to a neuro-ophthalmologist or uveitis specialist for evaluation of disc edema and were ultimately diagnosed with BSCR. RESULTS: Fifty-four eyes of 30 patients, from the practices of 15 uveitis specialists, met the eligibility criteria. In addition to disc edema, concomitant features in all patients included vitritis, chorioretinal lesions, and retinal vasculitis. Visual recovery to 20/40 or better occurred in 26 of 29 patients. Visual acuity remained 20/100 or worse in 2 patients previously diagnosed with idiopathic intracranial hypertension, 1 patient previously diagnosed with optic neuritis, and 1 patient for whom treatment was delayed for years, leading to optic disc atrophy. CONCLUSIONS: Optic disc edema is a presenting feature in some cases of BSCR. A diagnosis of BSCR should be considered when disc edema occurs with vitritis, chorioretinal inflammation, and retinal vasculitis. Patients should be referred to a uveitis specialist for treatment.

Oscillatory potentials in patients with birdshot chorioretinopathy.

PURPOSE: The electroretinogram (ERG) has proven to be useful in the evaluation and monitoring of patients with posterior uveitis. ERG oscillatory potentials (OPs) are sometimes reduced in many uveitic eyes with otherwise grossly normal ERG responses. This study compares ERG parameters, including OPs, between patients with birdshot chorioretinopathy, other posterior uveitis, and controls. METHODS: This was a retrospective case-control study. Sixty-four patients seen at a clinical practice had a total of 93 visits during which ERG was performed on both eyes. ERG data from 93 age-matched controls were also collected. Root-mean-squared (RMS) energy of the OPs was calculated using Fourier analysis for 88 patients and 88 age-matched controls for whom complete data were available. Photopic flicker amplitudes, photopic flicker latencies, scotopic b-wave amplitudes, and OP RMS values were compared between patients and controls. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves. RESULTS: The mean ages of patients and controls were 55.9 ± 10.8 (SD) years and 55.1 ± 11.5, respectively. 83% of the patients had a diagnosis of BCR. The mean OP RMS value was significantly different in patients (15.6 µV ± 9.7 µV) versus control eyes (33.0 µV ± 12.7 µV), p < 0.001. Area under the ROC curves (AUROC) was 0.75 for photopic flicker amplitudes, 0.77 for photopic flicker latencies, 0.72 for scotopic b-wave amplitudes, and 0.88 for OP RMS. AUROC was significantly different between OP RMS and photopic flicker amplitudes (p < 0.001), between OP RMS and flicker latencies (p = 0.0032), and between OP RMS and scotopic b-wave amplitudes (p < 0.0001). CONCLUSION: Analysis of OPs shows greater sensitivity and specificity in the diagnosis and evaluation of patients with birdshot chorioretinopathy than photopic and scotopic ERG amplitudes and photopic flicker latencies.

Nab-paclitaxel-induced cystoid macular edema in a patient with pre-existing optic neuropathy.

Paclitaxel is a widely used chemotherapy agent that has rarely been associated with ophthalmic toxicities. Cystoid macular edema is one such rare side effect of paclitaxel therapy. Its pathophysiology remains poorly understood. Here, we report on a 69-year-old woman who developed cystoid macular edema associated with the albumin-bound formulation of paclitaxel after several months of therapy for breast cancer. After 2 months of drug withdrawal, her vision improved and there was a significant improvement in the macular edema by imaging with spectral-domain optical coherence tomography. Oncologists using taxane agents should be aware of this rare adverse outcome for timely patient referral to an ophthalmologist and appropriate treatment to preserve a patient's visual acuity.

EXPANDED CLINICAL SPECTRUM OF MULTIPLE EVANESCENT WHITE DOT SYNDROME WITH MULTIMODAL IMAGING.

PURPOSE: To evaluate and characterize multiple evanescent white dot syndrome abnormalities with modern multimodal imaging modalities. METHODS: This retrospective cohort study evaluated fundus photography, fluorescein angiography, indocyanine green angiography, optical coherence tomography, enhanced depth imaging optical coherence tomography, short-wavelength autofluorescence, and near-infrared autofluorescence. RESULTS: Thirty-four multiple evanescent white dot syndrome patients with mean age of 28.7 years were studied (range, 14-49 years). Twenty-six patients were women, and eight were men. Initial mean visual acuity was 0.41 logMAR. Final mean visual acuity was 0.03 logMAR. Fluorescein angiography shows a variable number of mid retinal early fluorescent dots distributed in a wreathlike pattern, which correlate to fundus photography, fundus autofluorescence, and indocyanine green angiography. Indocyanine green angiography imaging shows the dots and also hypofluorescent, deeper, and larger spots, which are occasionally confluent, demonstrating a large plaque of deep retinal hypofluorescence. Optical coherence tomography imaging shows multifocal debris centered at and around the ellipsoid layer, corresponding to the location of spots seen with photography, indocyanine green angiography, and fluorescein angiography. Protrusions of the hyperreflectant material from the ellipsoid layer toward the outer nuclear layer correspond to the location of dots seen with photography, indocyanine green angiography, and fluorescein angiography. CONCLUSION: Multimodal imaging analysis of the retina in patients with multiple evanescent white dot syndrome shows additional features that may help in the diagnosis of the disease and in further understanding its etiology. Multiple evanescent white dot syndrome is predominantly a disease of the outer retina, centered at the ellipsoid zone, but also involving the interdigitation zone and the outer nuclear layer.

New best1 mutations in autosomal recessive bestrophinopathy.

PURPOSE: To report the ocular phenotype in patients with autosomal recessive bestrophinopathy and carriers, and to describe novel BEST1 mutations. METHODS: Patients with clinically suspected and subsequently genetically proven autosomal recessive bestrophinopathy underwent full ophthalmic examination and investigation with fundus autofluorescence imaging, spectral domain optical coherence tomography, electroretinography, and electrooculography. Mutation analysis of the BEST1 gene was performed through direct Sanger sequencing. RESULTS: Five affected patients from four families were identified. Mean age was 16 years (range, 6-42 years). All affected patients presented with reduced visual acuity and bilateral, hyperautofluorescent subretinal yellowish deposits within the posterior pole. Spectral domain optical coherence tomography demonstrated submacular fluid and subretinal vitelliform material in all patients. A cystoid maculopathy was seen in all but one patient. In 1 patient, the location of the vitelliform material was seen to change over a follow-up period of 3 years despite relatively stable vision. Visual acuity and fundus changes were unresponsive to topical and systemic carbonic anhydrase inhibitors and systemic steroids. Carriers had normal ocular examinations including normal fundus autofluorescence. Three novel mutations were detected. CONCLUSION: Three novel BEST1 mutations are described, suggesting that many deleterious variants in BEST1 resulting in haploinsufficiency are still unknown. Mutations causing autosomal recessive bestrophinopathy are mostly located outside of the exons that usually harbor vitelliform macular dystrophy-associated dominant mutations.

Redefining multifocal choroiditis and panuveitis and punctate inner choroidopathy through multimodal imaging.

PURPOSE: To evaluate the characteristics of multifocal choroiditis and panuveitis (MCP) and punctate inner choroidopathy (PIC) using multimodal imaging. METHODS: This is a retrospective, consecutive, observational case series of 38 eyes of 22 patients. Each eye of patients with multiple yellow-white idiopathic inflammatory lesions in the fundus was classified as having MCP or PIC using standard diagnostic criteria in a masked fashion. The features of these eyes as determined from color fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, and angiography were compared across diagnostic categories. The main outcome measures were the features of both MCP and PIC as evidenced by multimodal imaging. RESULTS: Of the 38 eyes, 23 eyes had MCP, 15 had PIC; and 7 patients had a discordant pairing of one diagnosis in 1 eye with the other diagnosis in the fellow eye. Acute lesions appeared as nodular collections under the retinal pigment epithelium. These solid retinal pigment epithelium detachments appeared to rupture leading to inflammatory infiltration of the subretinal space and outer retina, often with a widespread loss of the outer retinal architecture beyond the confines of the inflammatory exudate. Treatment with corticosteroids caused a rapid regression of this material with a slower resolution of the abnormalities of the outer retinal architecture. The pattern of inflammatory involvement seen by multimodal imaging did not vary between PIC and MCP. No consistent abnormalities were seen in the choroid in either condition, although there was slight thickening of the choroid underlying some acute lesions. CONCLUSION: Despite the names of these diseases, the principle sites involved appears to be the subretinal pigment epithelium and outer retinal spaces. Because both MCP and PIC target the same essential structures in the same phenotypic manner and, when active, are treated the same way, there seems to be limited clinical utility in trying to differentiate them. Based on multimodal imaging results, a reappraisal of pathogenic features and naming conventions of these diseases seems indicated.

Outer retinal tubulation in degenerative retinal disorders.

PURPOSE: To demonstrate outer retinal tubulation (ORT) in various degenerative retinal disorders. METHODS: This was a retrospective review of the multimodal imaging of 29 eyes of 15 patients with various retinal dystrophies and inflammatory maculopathies manifesting ORT. The morphologic features of ORT and its evolution over time were analyzed using spectral-domain optical coherence tomography data. RESULTS: Outer retinal tubulation was identified as round or ovoid structures with hyperreflective borders in pattern dystrophy (six eyes), acute zonal occult outer retinopathy (five eyes), retinitis pigmentosa (four eyes), Stargardt disease (four eyes), gyrate atrophy (two eyes), choroideremia (two eyes), and various other degenerative conditions. These structures appeared to develop from the invagination of photoreceptors at the junction of intact and atrophic outer retina. During follow-up, the number and distribution of ORT largely remained stable. As zones of atrophy enlarged, the frequency of ORT appeared to increase. The ORT structures were found in <10% of patients with retinitis pigmentosa, Stargardt disease, or pattern dystrophy. CONCLUSION: Outer retinal tubulation is found in various degenerative retinal disorders that share in common damage to the outer retina and/or retinal pigment epithelium. The presence of ORT may be an indicator of underlying disease stage and severity.

Chronic retinal necrosis: cytomegalovirus necrotizing retinitis associated with panretinal vasculopathy in non-HIV patients.

PURPOSE: To characterize a unique cytomegalovirus (CMV)-associated retinopathy in patients with limited immune dysfunction. METHODS: Retrospective observational case series. CMV was confirmed as the pathogenic agent via polymerase chain reaction analysis of aqueous or vitreous humor samples or via immunohistochemical analysis of retinal biopsy specimens. RESULTS: Five non-HIV patients with granular necrotizing retinitis, vitritis, and severe occlusive vasculopathy were identified. Patient histories all suggested a basis for limited immune dysfunction including advanced age (n = 4), diabetes mellitus (n = 4), and noncytotoxic immunotherapy (n = 3). Diagnosis of CMV retinitis was delayed in all cases and patients received either no antiviral therapy (n = 2) or incorrect antiviral therapy (n = 3) for presumed herpes simplex/varicella zoster-related acute retinal necrosis. Retinitis subsequently regressed in all cases with introduction of systemic ganciclovir/valganciclovir (n = 5) and/or intravitreal foscarnet (n = 2). Four of five patients developed neovascularization because of extensive retinal ischemia. CONCLUSION: The clinical expression of CMV-associated retinopathy is strongly related to immune status. In patients with limited immune dysfunction, a mixed clinical picture of intraocular inflammation with panretinal occlusive vasculopathy, more characteristic of acute retinal necrosis, and peripheral slowly progressive granular retinitis, more characteristic of classic CMV retinitis, is observed. Recognition of this atypical clinical presentation, which the authors term chronic retinal necrosis, should prompt molecular testing for CMV to determine the appropriate antiviral therapy. Consideration should also be given to prophylactic panretinal photocoagulation in such eyes, given the high risk of neovascular complications.

Initial Occurrence of Bilateral Anterior Uveitis in a Patient with Juvenile Idiopathic Arthritis following Discontinuation of Topical Steroids after Bilateral Strabismus Surgery.

Post-operative inflammation is a well-known complication of intraocular surgery. This is especially true in patients with a prior history of uveitis or with a predisposition for an inflammatory response. We report the first published case of a patient who developed bilateral anterior uveitis after bilateral strabismus surgery. It was the first episode of uveitis for this patient who had a pre-existing diagnosis of juvenile idiopathic arthritis.

Novel Case of Multifocal Choroiditis following Powassan Virus Infection.

PURPOSE: To present a case study that describes novel ocular manifestations of Powassan virus encephalitis using fundus imaging. STUDY DESIGN: Case Report. RESULTS: In this case study, fundus photographs, fundus autofluorescence, and fluorescein angiography were used to highlight Powassan virus-induced multifocal choroiditis with linear streaks. CONCLUSIONS: Our case study demonstrates novel retinal findings of Powassan virus, a pattern which is commonly described in eyes infected with West Nile Virus, another type of flavivirus.

Adolescents of the U.S. National Longitudinal Lesbian Family Study: sexual orientation, sexual behavior, and sexual risk exposure.

This study assessed Kinsey self-ratings and lifetime sexual experiences of 17-year-olds whose lesbian mothers enrolled before these offspring were born in the longest-running, prospective study of same-sex parented families, with a 93% retention rate to date. Data for the current report were gathered through online questionnaires completed by 78 adolescent offspring (39 girls and 39 boys). The adolescents were asked if they had ever been abused and, if so, to specify by whom and the type of abuse (verbal, emotional, physical, or sexual). They were also asked to specify their sexual identity on the Kinsey scale, between exclusively heterosexual and exclusively homosexual. Lifetime sexual behavior was assessed through questions about heterosexual and same-sex contact, age of first sexual experience, contraception use, and pregnancy. The results revealed that there were no reports of physical or sexual victimization by a parent or other caregiver. Regarding sexual orientation, 18.9% of the adolescent girls and 2.7% of the adolescent boys self-rated in the bisexual spectrum, and 0% of girls and 5.4% of boys self-rated as predominantly-to-exclusively homosexual. When compared with age- and gender-matched adolescents of the National Survey of Family Growth, the study offspring were significantly older at the time of their first heterosexual contact, and the daughters of lesbian mothers were significantly more likely to have had same-sex contact. These findings suggest that adolescents reared in lesbian families are less likely than their peers to be victimized by a parent or other caregiver, and that daughters of lesbian mothers are more likely to engage in same-sex behavior and to identify as bisexual.

TREATMENT OF REFRACTORY TUBERCULAR SERPIGINOUS-LIKE CHOROIDITIS WITH INTRAVITREAL METHOTREXATE.

PURPOSE: To describe a case of tubercular serpiginous-like choroiditis that progressed, despite antitubercular medication, corticosteroids, and immunomodulatory treatment, which ultimately quieted after two intravitreal methotrexate injections. METHODS: Case report. RESULTS: A 35-year-old woman reported a shadow in the left eye for 2 weeks. She presented with tubercular serpiginous-like choroiditis in the right eye 2 years prior. At that time, she was started on antituberculosis therapy but was noncompliant and lost to follow-up. On re-presentation, there was a new active left-eye serpiginous lesion, with repeat positive QuantiFERON gold testing. Four antituberculosis drugs were started, followed by corticosteroids and azathioprine, with continued progression despite aggressive treatment. She was finally given 2 intravitreal methotrexate injections (400 µg/0.1 cc) 1 month apart, with final arrest of lesion extension. The uveitis remained quiet for over 24 months, and the patient was able to discontinue all systemic therapy. CONCLUSION: Intravitreal methotrexate injections halted progression of treatment-refractory tubercular serpiginous-like choroiditis.

TUBERCULOUS CHOROIDITIS IN PATIENT WITH VOGT-KOYANAGI-HARADA DISEASE.

PURPOSE: To describe a novel case of intraocular tuberculosis (TB) arising in a patient undergoing treatment for Vogt-Koyanagi-Harada disease, and to highlight the use of spectral domain optical coherence tomography for helping confirm the diagnosis and monitor treatment response. METHODS: Case report of a patient with Vogt-Koyanagi-Harada disease on prednisone, with acute clinical changes suspicious for bilateral tuberculous choroiditis. Spectral optical coherence tomography, fundus photography, and B-scan ultrasonography were all used to capture the acute lesions, and to monitor their responses after initiation of anti-TB therapy. RESULTS: New subretinal lesions arose bilaterally, as characterized by spectral domain optical coherence tomography, and appeared to regress after a first round of anti-TB therapy, thereby helping confirm the presumed diagnosis of intraocular TB. A new peripheral choroidal lesion arose shortly after temporary cessation of antimicrobial treatment, and again regressed once four-drug therapy was instituted, with no recurrent lesions thereafter. CONCLUSION: The use of multimodal imaging was instrumental in the management of a rare case of intraocular TB arising in the setting of underlying Vogt-Koyanagi-Harada disease.

MULTIMODAL IMAGING OF IGG4-RELATED PAPILLITIS AND RETINAL DISEASE.

PURPOSE: To report a case of IgG4-related ophthalmic disease, which presented with papillitis and subretinal deposits. METHODS: Observational case report with multimodal imaging. RESULTS: A 52-year-old man with a history of persistent lymphadenopathy presented with decreased vision in his left eye. Funduscopic examination demonstrated cuticular drusen in both eyes and florid edema of the left optic nerve, along with scattered circumscribed grey-yellow subretinal deposits that were distinct from the cuticular drusen. Swept-source optical coherence tomography demonstrated a hyper-reflective subretinal material corresponding to the grey-yellow subretinal deposits on clinical examination along with diffuse outer retinal disruption. Fundus autofluorescence revealed scattered hypoautofluorescence corresponding to cuticular drusen and also larger patches of hypoautofluorescence corresponding to the grey-yellow subretinal deposits. Fluorescein angiography demonstrated hypofluorescence corresponding to the large subretinal deposits and leakage at the optic nerve. Lymph node biopsy demonstrated IgG4-positive plasma cells and elevated serum IgG4 levels leading to a diagnosis of IgG4-related ophthalmic disease. The patient was treated with oral prednisone with subsequent resolution of the optic nerve edema. CONCLUSION: We describe multimodal imaging of unique retinal and optic nerve findings associated with IgG4-related ophthalmic disease. Our report broadens the spectrum of ocular involvement associated with IgG4-related disease.

Trends in State Policy Support for Sexual Minorities and HIV-Related Outcomes Among Men Who Have Sex With Men in the United States, 2008-2014.

BACKGROUND: To examine trends in state-level policy support for sexual minorities and HIV outcomes among men who have sex with men (MSM). METHODS: This longitudinal analysis linked state-level policy support for sexual minorities [N = 94 metropolitan statistical areas (MSAs) in 38 states] to 7 years of data (2008-2014) from the Centers for Disease Control and Prevention on HIV outcomes among MSM. Using latent growth mixture modeling, we combined 11 state-level policies (eg, nondiscrimination laws including sexual orientation as a protected class) from 1999 to 2014, deriving the following 3 latent groups: consistently low policy support, consistently high policy support, and increasing trajectory of policy support. Outcomes were HIV diagnoses per 10,000 MSM, late diagnoses (number of deaths within 12 months of HIV diagnosis and AIDS diagnoses within 3 months of HIV diagnosis) per 10,000 MSM, AIDS diagnoses per 10,000 MSM with HIV, and AIDS-related mortality per 10,000 MSM with AIDS. RESULTS: Compared with MSAs in states with low policy support and increasing policy support for sexual minorities, MSAs in states with the highest level of policy support had lower risks of HIV diagnoses [risk difference (RD) = -37.9, 95% confidence interval (CI): -54.7 to -21.0], late diagnoses (RD = -12.5, 95% CI: -20.4 to -4.7), and AIDS-related mortality (RD = -33.7, 95% CI: -61.2 to -6.2), controlling for time and 7 MSA-level covariates. In low policy support states, 27% of HIV diagnoses, 21% of late diagnoses, and 10% of AIDS deaths among MSM were attributable to the policy climate. CONCLUSION: The state-level policy climate related to sexual minorities was associated with HIV health outcomes among MSM and could be a potential public health tool for HIV prevention and care.