A genotype-phenotype correlation matrix for ABCA4 disease based on long-term prognostic outcomes.

BackgroundMore than 1500 variants in the ATP-binding cassette, sub-family A, member 4 (ABCA4), locus underlie a heterogeneous spectrum of retinal disorders ranging from aggressive childhood-onset chorioretinopathy to milder late-onset macular disease. Genotype-phenotype correlation studies have been limited in clinical applicability as patient cohorts are typically small and seldom capture the full natural history of individual genotypes. To overcome these limitations, we constructed a genotype-phenotype correlation matrix that provides quantifiable probabilities of long-term disease outcomes associated with specific ABCA4 genotypes from a large, age-restricted patient cohort.MethodsThe study included 112 unrelated patients at least 50 years of age in whom 2 pathogenic variants were identified after sequencing of the ABCA4 locus. Clinical characterization was performed using the results of best corrected visual acuity, retinal imaging, and full-field electroretinogram testing.ResultsFour distinct prognostic groups were defined according to the spatial severity of disease features across the fundus. Recurring genotypes were observed in milder prognoses, including a newly defined class of rare hypomorphic alleles. PVS1 (predicted null) variants were enriched in the most severe prognoses; however, missense variants were present in a larger-than-expected fraction of these patients. Analysis of allele combinations and their respective prognostic severity showed that certain variants, such as p.(Gly1961Glu), and both rare and frequent hypomorphic alleles, were "clinically dominant" with respect to patient phenotypes irrespective of the allele in trans.ConclusionThese results provide much-needed structure to the complex genetic and clinical landscape of ABCA4 disease and add a tool to the clinical repertoire to quantitatively assess individual genotype-specific prognoses in patients.FUNDINGNational Eye Institute, NIH, grants R01 EY028203, R01 EY028954, R01 EY029315, P30 19007 (Core Grant for Vision Research); the Foundation Fighting Blindness USA, grant no. PPA-1218-0751-COLU; and Research to Prevent Blindness.

ACUTE SYPHILITIC POSTERIOR PLACOID CHORIORETINITIS: MULTIMODAL IMAGING AND ELECTROPHYSIOLOGIC FINDINGS BEFORE AND AFTER TREATMENT.

PURPOSE: To describe the clinical course of acute syphilitic posterior placoid chorioretinitis (ASPPC) in the preplacoid stage, placoid stage, and after treatment with penicillin. METHOD: A retrospective case report of serial multimodal imaging and electrophysiology studies of a patient with ASPPC, with 18 months of follow-up. RESULTS: A 47-year-old man presented with bilateral panuveitis. The patient defaulted follow-up and returned when his vision deteriorated. Tests for neurosyphilis and retroviral disease were positive, and treatment was initiated. The earliest change on serial optical coherence tomography was loss of the signal from the reflective band corresponding to the ellipsoid zone. In the placoid stage, there was nodular thickening of the retinal pigment epithelium. The ellipsoid zone signals reappeared after treatment. Fundus fluorescein angiogram at presentation showed peripapillary vasculitis and disk leakage; indocyanine green angiography revealed multiple hypofluorescent spots in the peripapillary region and posterior pole that was not visible clinically. The angiographic abnormalities resolved after treatment. Electrophysiology demonstrated bilateral maculopathy and reduction of both a- and b-waves from dark-adapted and light-adapted responses at presentation. The b-waves (inner retina) recovered partially with treatment. CONCLUSION: To the best of our knowledge, this is the first case report of the multimodal imaging and electrophysiology findings in a patient with acute syphilitic posterior placoid chorioretinitis, before the development of the classic placoid lesion. Improvement of structural and functional pathology after systemic treatment is demonstrated.

Ocular Outcome of Brazilian Patients With Congenital Toxoplasmosis.

BACKGROUND: Retinochoroiditis is the most frequent manifestation of congenital toxoplasmosis. We aimed to describe the ocular outcome and factors that may influence the visual prognosis of these patients. METHODS: Cohort of patients with confirmed congenital toxoplasmosis seen between 1996 and 2017 in Porto Alegre, southern Brazil. RESULTS: Seventy-seven patients were included, of which 65 (85.5%) were identified by routine screening. Median age at the end of the follow-up was 10 years (minimum 2, maximum 25). Retinochoroiditis was present in 55 patients (71.4%). New retinochoroidal lesions developed after the first year of life in 77.8% of the patients who began treatment after the fourth month of life, compared with 35.2% among those treated before 4 months of life (relative risk = 0.45, 95% confidence intervals: 0.27-0.75, P = 0.02) and 33.3% among those treated before 2 months of life (relative risk = 0.42, 95% confidence intervals: 0.25-0.72, P = 0.01). There was a peak incidence of new retinochoroidal lesions between 4 and 5 years and another peak between 9 and 14 years, the latter only among girls. Thirty-four patients with retinochoroiditis were followed up for 10 years or more, and the school performance was appropriate in 28 (82.4%). CONCLUSIONS: The high incidence of new retinochoroidal lesions during the follow-up period indicates the importance of long-term follow-up of patients with congenital toxoplasmosis. Initiating treatment within the first 4 months of life, especially within the first 2 months, was a protective factor against the later development of retinochoroiditis. Despite the usual favorable prognosis, the high morbidity of congenital toxoplasmosis in Brazil was confirmed.

Unilateral Birdshot Chorioretinopathy in an Elderly Patient.

[Full article available at http://rimed.org/rimedicaljournal-2019-02.asp].

Eccentric fixation patterns, clinical findings, and reading speed in patients with bilateral toxoplasmic macular retinochoroiditis / Padrões de fixação excêntrica, achados clínicos e velocidade de leitura em pacientes com retinocoroidite macular bilateral por toxoplasmose

ABSTRACT Purpose: To study visual acuity, refractive errors, eccentric fixation, and reading performance in patients with toxoplasmic macular retinochoroiditis. Methods: Twenty-three participants with bilateral toxoplasmic macular retinochoroiditis and 4 with toxoplasmic macular retinocho­roiditis in their unique eye were evaluated. Participants reported their eye dominance, confirmed by the Portus and Miles test. Best corrected visual acuity, spherical equivalent refraction, magnification need, and reading speed were measured. Microperimetry (MAIA, Centervue - Padova, Italy) recorded the preferred retinal locus and fixation stability by means of the bivariate contour ellipse area. Fourteen eyes from 14 normally sighted subjects served as controls. Results: Mean ± SD best corrected visual acuity was better in the dominant eye than in the nondominant eye: 0.9 ± 0.2 (logMAR 0.5 to 1.4) vs. 1.2 ± 0.3 (logMAR 0.6 to 1.7) (p<0.0001, paired t-test). Spherical equivalent myopia of -4.00 or higher was present in 42% of the eyes. Microperimetry was performed in 42 eyes. Eccentric fixation was observed in all examined eyes. In 14 eyes (33%), the preferred retinal locus was placed (in the retina) superior temporal to the macular lesion, in 10 (24%) superior nasal, in 6 (14%) inferior temporal, and in 12 (28%) inferior nasal. There was no significant difference in the distribution of the preferred retinal locus position between dominant and nondominant eyes (p=0.85, Pearson test). There was no correlation between reading speed and the distance between the preferred retinal locus and the estimated original foveal position (r=-0.09; p=0.73), the bivariate contour ellipse area (r=-0.19; p=0.44), or best corrected visual acuity (r=0.024; p=0.92). Conclusions: Myopia is more prevalent in patients with toxoplasmic macular retinochoroiditis. Reading speed is not dependent on preferred retinal locus position, stability, or visual acuity. Nevertheless, documentation of fixation provides new data on the impact of visual impairment in these patients and may be useful for rehabilitation efforts.

RESUMO Objetivo: Estudar a acuidade visual, erros de refração, fixação excêntrica e desempenho de leitura em pacientes com retinocoroidite macular por Toxoplasmose. Métodos: Vinte e três pacientes com retinocoroidite macular por Toxoplasmose bilateral e quatro com retinocoroidite macular por Toxoplasmose no seu único olho foram avaliados. Os participantes relataram sua dominância ocular, confirmada pelo teste de Portus e Miles. A acuidade visual melhor corrigida, refração em equivalente esférico, magnificação necessária e velocidade de leitura foram medidas. A microperimetria (MAIA, Centervue - Padova, Italy) registrou a estabilidade preferida do locus e da fixação da retina por meio da área da elipse de con­torno bivariada. Quatorze olhos de 14 pacientes com boa visão serviram como controles. Resultados: A média ± DP da acuidade visual melhor corrigida foi melhor no olho do­minante do que no não dominante: 0,9 ± 0,2 (logMAR 0,5 a 1,4) vs. 1,2 ± 0,3 (logMAR 0,6 a 1,7) (p<0,0001, teste t pareado). Miopia em equivalente esférico de -4,00 ou maior estava presente em 42% dos olhos. Microperimetria foi realizada em 42 olhos. Fixação excêntrica foi observada em todos os olhos examinados. Em 14 olhos (33%), o locus retiniano preferencial estava localizado, na retina, na região súpero-temporal à lesão macular, em 10 (24%) súpero-nasal, em 6 (14%) ínfero-temporal, e em 12 olhos (29%) ínfero-nasal. Não houve diferença significativa na distribuição da posição do locus retiniano preferencial entre olhos dominantes e não dominantes (p=0,85, teste de Pearson). Não houve correlação entre velocidade de leitura e distância entre o locus retiniano preferencial e a posição foveal original estimada (r=-0,09; p=0,73), a área bivariada de contorno elipsóide (r=-0,19; p=0,44) ou acuidade visual melhor corrigida (r=0,024; p=0,92). Conclusões: A miopia é mais prevalente em pacientes com retinocoroidite macular por Toxoplasmose. A velocidade de leitura não é dependente da posição do locus retiniano preferencial, da estabilidade ou da acuidade visual. A documentação do padrão de fixação excêntrica, entretanto, oferece novos dados no impacto da deficiência visual nesses pacientes e pode ser útil em estratégias de reabilitação.

Eccentric fixation patterns, clinical findings, and reading speed in patients with bilateral toxoplasmic macular retinochoroiditis.

PURPOSE: To study visual acuity, refractive errors, eccentric fixation, and reading performance in patients with toxoplasmic macular retinochoroiditis. METHODS: Twenty-three participants with bilateral toxoplasmic macular retinochoroiditis and 4 with toxoplasmic macular retinocho-roiditis in their unique eye were evaluated. Participants reported their eye dominance, confirmed by the Portus and Miles test. Best corrected visual acuity, spherical equivalent refraction, magnification need, and reading speed were measured. Microperimetry (MAIA, Centervue - Padova, Italy) recorded the preferred retinal locus and fixation stability by means of the bivariate contour ellipse area. Fourteen eyes from 14 normally sighted subjects served as controls. RESULTS: Mean ± SD best corrected visual acuity was better in the dominant eye than in the nondominant eye: 0.9 ± 0.2 (logMAR 0.5 to 1.4) vs. 1.2 ± 0.3 (logMAR 0.6 to 1.7) (p<0.0001, paired t-test). Spherical equivalent myopia of -4.00 or higher was present in 42% of the eyes. Microperimetry was performed in 42 eyes. Eccentric fixation was observed in all examined eyes. In 14 eyes (33%), the preferred retinal locus was placed (in the retina) superior temporal to the macular lesion, in 10 (24%) superior nasal, in 6 (14%) inferior temporal, and in 12 (28%) inferior nasal. There was no significant difference in the distribution of the preferred retinal locus position between dominant and nondominant eyes (p=0.85, Pearson test). There was no correlation between reading speed and the distance between the preferred retinal locus and the estimated original foveal position (r=-0.09; p=0.73), the bivariate contour ellipse area (r=-0.19; p=0.44), or best corrected visual acuity (r=0.024; p=0.92). CONCLUSIONS: Myopia is more prevalent in patients with toxoplasmic macular retinochoroiditis. Reading speed is not dependent on preferred retinal locus position, stability, or visual acuity. Nevertheless, documentation of fixation provides new data on the impact of visual impairment in these patients and may be useful for rehabilitation efforts.

Use of En Face Swept-Source Optical Coherence Tomography Angiography in Identifying Choroidal Flow Voids in 3 Patients With Birdshot Chorioretinopathy.

Importance: Patients with birdshot chorioretinopathy (BSCR) can experience a delay in diagnosis owing to the challenges of identifying the condition prior to evolution of characteristic choroidal scars. An objective, noninvasive method for detecting early lesions in BSCR might have an effect on preventing vision loss in these patients. Objective: To test the feasibility of swept-source optical coherence tomography angiography (SS-OCTA) in the detection of BSCR choroidal lesions and to use en face image analysis of choroidal layers to localize lesion depth. Design, Setting, and Participants: Prospective, longitudinal, observational case series of 3 patients diagnosed as having BSCR at 1 of 2 tertiary care uveitis centers between August 2017 and October 2017. Exposures: Widefield SS-OCTA and indocyanine green angiography (ICGA). Main Outcomes and Measures: En face SS-OCTA slabs through the choroid were evaluated for the presence of flow voids corresponding to hypocyanescent lesions by ICGA. Baseline and posttreatment images were compared. Results: Six eyes of 3 patients with previously undiagnosed and untreated BSCR were imaged at baseline and after initiation of immune modulation treatment. Two patients had a history of recent-onset BSCR, and the third patient had a history of chronic untreated disease of at least 5 years' duration. All patients were white and between the ages of 50 and 67 years. All eyes demonstrated multiple flow voids on en face SS-OCTA images that corresponded with hypocyanescent lesions by ICGA. Analysis of serial depth en face SS-OCTA flow images identified that in the acute-onset patients, flow voids were located adjacent to large vessels in the Haller layer and regressed with treatment. In the patient with chronic, untreated disease, full-thickness choroidal flow voids were identified that did not regress with treatment. Conclusions and Relevance: For these 3 patients, SS-OCTA provided a noninvasive method for identifying early BSCR lesions previously visible only with ICGA. The depth information provided by SS-OCTA suggests acute lesions originate in the Haller layer, and that in the absence of treatment, damage extends up thorough the superficial choroid, and ultimately to the retinal pigment epithelium and retina. Swept-source OCTA may represent a new and noninvasive method for detecting and monitoring disease activity in BSCR.

Pregnancy-induced hypertension-related chorioretinitis resembling uveal effusion syndrome: A case report.

RATIONALE: Pregnancy-induced hypertension (PIH) is a major cause of maternal and fetal mortality. Hypertensive choroidopathy is a preliminary sign of vasogenic edema in the choroid, and is associated with PIH. Here, we report a post-natal case of PIH-related chorioretinitis with bilateral severe serous retinal detachment (SRD) resembling uveal effusion syndrome. PATIENT CONCERNS: A 35-year-old woman was diagnosed with severe PIH at 37 weeks of pregnancy. She underwent an emergency cesarean delivery. Four days after delivery, she perceived a sudden decrease of vision. At presentation, fundus examination demonstrated bullous SRD and multiple white mottles in the posterior poles of both eyes. Optical coherence tomography (OCT) showed macula edema and retinal pigment epithelium (RPE) folds. Indocyanine green angiography (ICGA) demonstrated delayed filling of choroidal circulation in the early phase and multiple hyperfluorescent spots in the mid phase. DIAGNOSES: PIH. INTERVENTIONS: Antihypertension treatment alone resulted in gradual resolution of the SRD. OUTCOMES: At 463 days after delivery, fundus photographs of both eyes showed leopard spots corresponding to hyperautofluorescent spots with dark rim observed on fundus autofluorescence images. LESSONS: Ophthalmologists should be aware of PIH-related chorioretinitis with similar clinical manifestations as uveal effusion syndrome, and should treat with antihypertensive agents in cooperation with obstetricians.

Intravenous Ceftriaxone for Syphilitic Uveitis.

PURPOSE: Report of clinical/multimodal imaging outcomes of patients with syphilitic uveitis alternatively treated with intravenous(IV) ceftriaxone, due to unavailability of penicillin G. METHODS: Chart review of all cases of syphilitic uveitis presenting to Hospital São Geraldo/HC-UFMG and treated with intravenous ceftriaxone, between January and August 2014. Clinical, serological and ophthalmological data were collected. RESULTS: Twelve consecutive patients with syphilitic uveitis receiving IV ceftriaxone were identified. All 24 eyes had active intraocular inflammation on clinical examination. All patients received IV ceftriaxone (2-4 g daily) for 14-21 days, supplemented with oral corticosteroid as needed in 9 patients (75%), after documented clinical response. Improvement in intraocular inflammation was seen in all 24 eyes, with median best-corrected visual acuity (BCVA) increasing from 20/50 to 20/20, after a mean follow-up of 5.3 months. CONCLUSION: IV ceftriaxone may be an effective alternative for treatment of syphilitic uveitis, in the setting of unavailability of penicillin G.

RETINAL CAPILLARY DENSITY IN PATIENTS WITH BIRDSHOT CHORIORETINOPATHY.

PURPOSE: To quantify retinal capillary density and determine its correlation with visual acuity in patients with birdshot chorioretinopathy (BCR). METHODS: Patients with BCR and age-matched controls were imaged using a commercially available spectral domain optical coherence tomography angiography system (RTVue- XR Avanti; Optovue, Inc). We used the integrated software of the optical coherence tomography angiography device to analyze the foveal avascular zone area and the capillary density in the full retina as well as in the superficial capillary plexus and deep capillary plexus. We assessed the correlation between these parameters and visual acuity. RESULTS: Seventy-four eyes of 42 study participants (37 eyes of 21 BCR and 37 eyes of 21 healthy subjects) were included in this observational cross-sectional study. Capillary density of the full retina, superficial capillary plexus, and deep capillary plexus were significantly decreased in BCR compared with the healthy control group (P < 0.01). Visual acuity in patients with BCR was significantly associated with the capillary density of the superficial capillary plexus, deep capillary plexus, and full retina (P < 0.01) but not with the area of the foveal avascular zone. CONCLUSION: The decrease in visual acuity in patients with BCR is associated with retinal vascular impairment. Vessel density of the retinal capillary plexuses may be a promising imaging biomarker for BCR disease severity.

Intravitreal Injection of Sulfamethoxazole and Trimethoprim Associated with Dexamethasone as an Alternative Therapy for Ocular Toxoplasmosis.

PURPOSE: To evaluate intravitreal injections of sulfamethoxazole/trimethoprim in association with dexamethasone for treating toxoplasmic retinochoroiditis. METHODS: Thirteen patients with active, recurrent ocular focal toxoplasmic retinochoroiditis and visual acuity worse than 20/63 in the affected eye were included. Ocular toxoplasmosis was diagnosed according to the classic clinical findings. The primary end point was the change in the final best-corrected visual acuity (BCVA). RESULTS: The intraocular inflammation decreased within 2 weeks after injection in all eyes and resolved in 8 (62%) eyes with only one injection after 30 days; the remaining eyes received two injections. In all eyes, the retinitis was inactive and no patient had decreased early treatment diabetic retinopathy study lines of BCVA at the final examination. CONCLUSION: The combination of intravitreal trimethoprim/sulfamethoxazole and dexamethasone might be an alternative treatment strategy in patients with toxoplasmic retinochoroiditis.

Safety profile and efficacy of tacrolimus in the treatment of birdshot retinochoroiditis: a retrospective case series review.

AIM: Evaluation of the use of tacrolimus in the treatment of birdshot retinochoroiditis (BRC) at a tertiary referral centre with the aim to describe its safety and efficacy. METHODS: The medical records of 25 patients diagnosed with BRC at uveitis service, Moorfields Eye Hospital, and who had received tacrolimus treatment were retrospectively reviewed. The main outcome measures of the study were (1) safety of tacrolimus in terms of side effects and (2) efficacy, as measured both by control of inflammation and visual function assessed by Humphrey visual fields and electrophysiological testing over at least 6 months and then 1 year. RESULTS: Tacrolimus was commenced in 25 patients (mean age 50.4±10.8 years) and was well tolerated in 21 patients (84%). It was necessary to stop the tacrolimus in four patients. No patient showed major changes in renal function: 3/21 patients (14.28%) showed slightly abnormal (less than 30%) function at the end of the first month of treatment; 1/21 (4.76%) patients at 3 months, but at the end of a 6-month treatment period only 1/21 patients (4.76%) showed minor abnormality in renal function. The mean daily prednisolone dose was 19.7 mg at the beginning of the study, which had fallen to 6.9 mg at the end (t=5.071, p=0.001). Visual acuity mostly remained stable. Visual fields improved over time (mean improvement in Humphrey mean deviation, right eye=1.8±2.4 dB, t=3.821, p=0.004; left eye=1.9±2.7, dB, t=3.06, p=0.007). Electrophysiological function showed improvement in 10 patients, and in four patients an initial deterioration in function improved following tacrolimus dose adjustment. CONCLUSION: Tacrolimus has a good safety profile for long-term use in patients with BRC as a second-line agent enabling steroid sparing and visual function stabilisation or improvement.

Multimodal Imaging in Birdshot Retinochoroiditis.

PURPOSE: To describe retinal vascular changes in Birdshot Retinochoroiditis (BSRC) with multimodal imaging techniques and functional values. METHODS: In this single-center study, 64 eyes of 32 subjects with BSRC were classified according to disease activity and duration and underwent imaging with spectral domain optical coherence tomography, fluorescein angiography, indocyanine green angiography, fundus autofluorescence, and optical coherence tomography angiography (OCTA). RESULTS: Mean age of the patients was 60 years (range, 38-74). OCTA revealed capillary loops (58%), telangiectatic vessels (44%), increased intercapillary spaces (52%), altered vascular architecture (53%), and rarefication of C-scans (63%) in retinal layers. Increased rarefications of C-scans (p = 0.0056; p = 0.0046) and altered vascular architecture (p = 0.0120; p = 0.0243) in superficial and deep capillary layers were significantly correlated with disease activity. CONCLUSION: OCTA adds new insights in a multimodal imaging approach of retinal vascular layer visualization in BSRC and may contribute to existing methods for diagnosing severity and potentially progression of the disease.

Fundus Autofluorescence Findings in Eyes With Birdshot Chorioretinitis.

Purpose: The purpose of this study was to describe fundus autofluorescence (FAF) findings in eyes with birdshot chorioretinitis (BSCR) and to compare findings to demographic, medical, and clinical characteristics. Methods: In this multicenter, prospective, cross-sectional study, 172 eyes (86 patients) with BSCR were investigated. Participants underwent a standardized evaluation including collection of demographic data, ophthalmic and treatment history, and ophthalmologic examination. Using a standardized protocol, hypo- and hyperautofluorescence in macular and extramacular regions and specific patterns of abnormal FAF could be scored for 167 eyes. Images were scored by two independent, masked graders. Measures of visual function included best-corrected visual acuity (BCVA), contrast sensitivity (CS), color vision, and Humphrey visual field mean deviation (HVF-MD). Results: Any abnormal FAF finding was observed in 132 eyes (79.0%); macular abnormalities were observed in 84 eyes (49.1%). The most common findings were peripapillary confluent hypoautofluorescence (122 eyes [73.1%]); extramacular granular hypoautofluorescence (100 eyes [59.9%]); and macular granular hypoautofluorescence (67 eyes [40.1%]). Confluent hypoautofluorescence was related to longer median disease duration (8.7 years) than granular hypoautofluorescence (7.9 years) or hyperautofluorescence (5.6 years). Macular confluent hypoautofluorescence was associated with BCVA ≤20/25 (odds ratio [OR] = 7.83, P = 0.007), BCVA ≤20/50 (OR = 4.94, P = 0.002), and abnormal CS (OR = 4.56, P = 0.009). Presence of macular or extramacular hypoautofluorescence was related to HVF-MD ≤-3 dB (OR = 2.43, P = 0.01 and OR = 2.89, P = 0.003, respectively). Conclusions: In this large cohort, various FAF abnormalities were found, indicating that disorders of the retinal pigment epithelium are features of BSCR. Abnormal FAF is a marker of visual dysfunction in the disease.

Choroidal Imaging with Swept-Source Optical Coherence Tomography in Patients with Birdshot Chorioretinopathy: Choroidal Reflectivity and Thickness.

PURPOSE: To characterize choroidal thickness and choroidal reflectivity in the eyes of patients with birdshot chorioretinopathy (BSCR). DESIGN: Cross-sectional observational study. PARTICIPANTS: Two hundred twenty BSCR patients and 59 healthy controls. METHODS: Patients with BSCR and healthy controls underwent imaging of the macula in both eyes with a swept-source optical coherence tomography device (DRI-OCT1 Atlantis; Topcon). Images were exported from the device, and analysis was performed by 2 graders in the Doheny Image Reading Center using Image J software. The choroidal thickness at the foveal center was measured. In addition, the inner and outer boundaries of the choroid and retinal pigment epithelium (RPE) as well as the inner retinal surface all were segmented to allow the brightness and reflectivity of the pixels in the choroid, RPE band, and overlying vitreous to be quantified. An adjusted or normalized choroidal reflectivity, with the RPE as the bright reference standard and the vitreous as the dark reference standard, was computed using the formula: normalized choroidal reflectivity = (choroidal reflectivity-vitreous reflectivity)/RPE reflectivity. MAIN OUTCOME MEASURES: Choroidal reflectivity and choroidal thickness. RESULTS: Three hundred eighty-six eyes in the BSCR group and 59 eyes in the control group were included in this analysis. Higher choroidal reflectivity and lower choroidal thickness were documented in inactive BSCR patients compared with active BSCR and controls (P < 0.01). Active BSCR patients showed lower choroidal thickness compared with controls (P < 0.01). There was a negative correlation between choroidal reflectivity and choroidal thickness (r = -0.793; P < 0.001). On multiple regression analysis, choroidal thickness, age, and disease duration (all P < 0.01) all were significant predictors of choroidal reflectivity. CONCLUSIONS: Choroidal reflectivity and choroidal thickness changes are evident in active and inactive BSCR patients. Novel choroidal parameters such as choroidal reflectivity may warrant further study in the setting of BSCR.

Analysis of autofluorescence pattern in birdshot chorioretinopathy.

PURPOSE: To characterize and correlate the different patterns of fundus autofluorescence (FAF) in patients with birdshot chorioretinopathy (BSCR), with functional and anatomical parameters. METHODS: Twenty-one BSCR patients were prospectively studied in 2013 and 2014. Each patient underwent visual acuity (VA) and visual field (SITA standard 30.2) testing as well as fluorescein and indocyanine green angiography, spectral-domain optical coherence tomography (SD-OCT) B scan, enhanced depth imaging (EDI), and fundus autofluorescence (FAF) imaging. The disease was classified as active, chronic, or quiescent. RESULTS: The patients' mean age was 60.3 ± 9.2 years and 60% were female. Disease duration was 5.7 ± 3.7 years. Autofluorescence imaging showed punctiform hyper-FAF spots in 23 out of the 29 eyes (79%), which was significantly associated with a greater visual field mean deviation (-7 ± 7 versus -3 ± 2 dB, p = 0.04). Hypo-FAF was defined as peripapillary (n = 25; 86.2%), macular (n = 10; 34.5%), lichenoid (n = 17; 58.6%), and/or diffuse (n = 13; 44.8%). Lichenoid hypo-FAF was significantly associated with worse VA (0.18 ± 0.24 vs. 0.05 ± 0.07 LogMAR, p = 0.04). Macular hypo-FAF was associated with a history of macular edema (62.5%; p = 0.06). Diffuse hypo-FAF was observed more frequently (p = 0.01) in chronic disease (66.7%) than in active (0%) or quiescent disease (27.3%). CONCLUSIONS: Autofluorescence analysis in BRSC patients contributes to evaluating disease activity and could be useful to guide follow-up and treatment.

Electroretinogram and visual field changes in a case of birdshot chorioretinopathy.

PURPOSE: This case report explores the role of the visual field perimetry and electroretinogram (ERG) in cases of non-infectious uveitis in the assessment and monitoring of retinal function and response to treatment. METHODS: A 59-year-old Caucasian female presenting with bilateral posterior uveitis newly diagnosed as birdshot chorioretinopathy (BSCR) presenting with bilateral decrease in visual acuity and cystoid macular edema, as well as a paracentral scotoma in the right eye. The diagnosis and follow-up of the case was done using visual field perimetry, optical coherence tomography (OCT), and ERG. RESULTS: Baseline ERG showed a marked decrease in the amplitudes of the scotopic and photopic responses and a delay of peak times mainly in the right eye. Mycophenolate mofetil at 2 g/day and oral prednisolone at 1 g/kg/day were administered with gradual tapering of the corticosteroids. After 5 months, there was a noticeable improvement in the visual acuity, macular edema in OCT, and an obvious increase in the amplitudes of the ERG associated with a decrease in peak times, particularly in the 30 Hz photopic 3.0 Flicker of the right eye. CONCLUSION: This case report highlights the importance of the peak time and wave amplitudes of the 30 Hz photopic DA 3.0 Flicker as being a sensitive parameter in the diagnosis and follow-up of BSCR.

Chorioretinal Lesions Presumed Secondary to Zika Virus Infection in an Immunocompromised Adult.

IMPORTANCE: Zika virus has spread rapidly throughout the Americas since 2015. The public health implications of Zika virus infection lend special importance to identifying the virus in unsuspected hosts. OBJECTIVE: To describe relevant imaging studies and clinical features of chorioretinal lesions that are presumably associated with Zika virus and that share analogous features with chorioretinal lesions reported in cases of Dengue fever and West Nile virus. DESIGN, SETTING, AND PARTICIPANTS: This is a case report from an academic referral center in Miami, Florida, of a woman in her 60s from Guaynabo, Puerto Rico, who presented with reduced visual acuity and bilateral diffuse, subretinal, confluent, placoid, and multifocal chorioretinal lesions. The patient was observed over a 5-month period. MAIN OUTCOMES AND MEASURES: Visual acuity, clinical course, and multimodal imaging study results. RESULTS: Fluorescein angiography revealed early hypofluorescence and late staining of the chorioretinal lesions. Optical coherence tomography demonstrated outer retinal disruption in the placoid macular lesions. Zika RNA was detected in a plasma sample by real-time reverse transcription polymerase chain reaction testing and was suspected to be the cause of chorioretinal lesions after other viral and infectious causes were ruled out. Three weeks after the onset of symptoms, the patient's visual acuity had improved to 20/60 OD and 20/25 OS, with intraocular pressures of 18 mm Hg OD and 19 mm Hg OS. In 6 weeks, the chorioretinal lesions had healed and visual acuity had improved to 20/25 OD and 20/20 OS. Follow-up optical coherence tomography demonstrated interval recovery of the outer retina and photoreceptors. CONCLUSIONS AND RELEVANCE: Acute-onset, self-resolving, placoid, or multifocal nonnecrotizing chorioretinal lesions may be a feature of active Zika virus chorioretinitis, as reported in other Flavivirus infections in adults. Similar findings in potentially exposed adults suggest that clinicians should consider IgM antibody or polymerase chain reaction testing for Zika virus as well as diagnostic testing for Dengue fever and West Nile virus.

Assessment of retinal vascular calibres as a biomarker of disease activity in birdshot chorioretinopathy.

PURPOSE: Birdshot chorioretinopathy (BCR) is a potentially blinding ocular disorder involving the retinal vasculature and choroid without any systemic manifestations. The objective of the study was to describe vascular calibre changes in BCR and analyse the possibility of this optical biomarker for staging and monitoring disease activity in BCR. METHODS: This retrospective case-control study at a tertiary referral eye centre in the UK included 33 eyes from 21 patients with BCR and equal number of eyes from control subjects. Diagnosis of BCR was confirmed on fundus fluorescein and indocyanine green angiography. Vascular calibres were measured using validated semiautomated software. RESULTS: Patients with BCR had smaller retinal venular calibres central retinal venular equivalent (CRVE) than controls (211.3 versus 227.9 µm, p = 0.008). After adjusting for variables, the difference between the two groups for CRVE at baseline was statistically significant based on two different analysis methods. Central retinal venular equivalent (CRVE) was lower at the 6-month follow-up visit (206.2 versus 213.8 µm, p-value = 0.03), and arteriole-to-venule ratio was larger (0.74 versus 0.71, p = 0.04) in subjects with BCR. Arteriolar calibre (CRAE) remained the same. CONCLUSION: This study provides novel insight into the pattern of vascular involvement in BCR. There was significant difference in the CRVE in patients with BCR. More studies are needed to correlate this data with visual function and treatment outcome and to validate the findings.