Cerebrovascular reactivity in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations.

Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic manifestations (RVCL-S) is a small vessel disease caused by TREX1 mutations. RVCL-S is characterized by retinal vasculopathy and brain white matter lesions with and without contrast enhancement. We aimed to investigate cerebrovascular reactivity (CVR) in RVCL-S. In this cross-sectional observational study, 21 RVCL-S patients, 23 mutation-negative family members, and 31 healthy unrelated controls were included. CVR to a hypercapnic challenge was measured using dual-echo arterial spin labeling magnetic resonance imaging. Stratified analyses based on age were performed. We found that CVR was decreased in gray and white matter of RVCL-S patients compared with family members and healthy controls (ANCOVA; P < 0.05 for all comparisons). This was most noticeable in RVCL-S patients aged ≥40 years (ANCOVA, P < 0.05 for all comparisons). In RVCL-S patients aged < 40 years, only CVR in white matter was lower when compared to healthy controls (P < 0.05). Gray matter CVR was associated with white matter lesion volume in RVCL-S patients (r = -0.527, P = 0.01). In conclusion, impaired cerebrovascular reactivity may play an important role in the pathophysiology of RVCL-S and may be an useful early biomarker of cerebrovascular disease severity.

Parafoveal Microvascular Alterations in Ocular and Non-Ocular BehÒ«et's Disease Evaluated With Optical Coherence Tomography Angiography.

Purpose: To compare quantitative optical coherence tomography angiography (OCT-A) measurements of the parafoveal microvasculature in retinal capillary plexuses among BehÒ«et uveitis (BU) patients, non-ocular BehÒ«et's disease (NOBD) patients, and healthy volunteers (HVs). Methods: Sixty-eight subjects were enrolled in this prospective observational cross-sectional study. OCT-A imaging was performed using the Heidelberg Engineering Spectralis OCT. A custom algorithm was developed to calculate the vessel density (VD) in three retinal vascular layers: deep capillary plexus, intermediate capillary plexus, and superficial vascular plexus. The foveal avascular zone (FAZ) and acircularity index were calculated for the whole retinal vascular complex. Results: We analyzed one eye from 21 BU patients (age, 51 ± 10 years), 23 NOBD patients (age, 48 ± 14 years), and 22 HVs (age, 44 ± 13 years). One-way multivariate analysis of covariance showed a statistically significant difference in VD among the three groups when combining the layers after controlling for scan quality (P < 0.001). The VD was lowest in the BU group and highest in the HV group in all layers. The FAZ area was also statistically significant different among the groups (P < 0.005), with the largest FAZ areas in BU patients and smallest FAZ areas in the HV group. However, no statistically significant difference was found for the acircularity index. Conclusions: The parafoveal microvasculature is affected not only in BU patients but also in NOBD patients. Most deviations in the retinal microcirculation in BehÒ«et patients were found in the deeper layers of the retina by using the quantitative VD measurement.

Combination of Intravenous Methotrexate and Methylprednisolone Therapy in the Treatment of Severe Ocular Inflammatory Diseases.

Purpose: To evaluate the efficacy of intravenous methotrexate and methylprednisolone in severe, sight-threatening ocular inflammatory conditions.Methods: This was a retrospective observational case series. Patients who had received intravenous methotrexate for ocular inflammation with at least 24 months of follow-up were included in the study.Results: Ten patients (20 eyes) were included in this study. Mean age of the patients was 47.2 ± 17.7 (range:19-74). At 1-month follow-up visit, nine patients showed improvement and one patient failed treatment. At 12-month follow-up visit, all patients were in remission. Two patients were only on intravenous methotrexate infusions. At twenty-four-month follow-up visit, only one patient, in remission, was on intravenous methotrexate therapy. Leukopenia was the only adverse effect observed.Conclusion: Intravenous methotrexate and methylprednisolone infusions can be an effective method of treatment in patients with severe, sight-threatening ocular inflammatory conditions.

Escalation to Weekly Adalimumab for the Treatment of Ocular Inflammation.

Purpose: To report the outcomes of the escalation of adalimumab (ADA) dose for refractory ocular inflammatory diseases.Methods: A retrospective case series of 15 patients (29 eyes) diagnosed with ocular inflammatory disease, including uveitis and scleritis, which was not adequately controlled with standard, every other week ADA dosing, leading to an escalation to weekly dosing.Results: Ten of fifteen patients escalated to weekly ADA achieved control of their inflammation; neither of the two patients increased for control of cystoid macular edema (CME) had resolution and required regional corticosteroids. One patient discontinued weekly ADA due to serious infection. The median length of follow up was 12 months.Conclusion: Our series suggests that the escalation of ADA can be a useful strategy for treating recalcitrant ocular inflammation, but may not be adequate to treat refractory CME.

Multimodal Imaging Characteristics and Functional Test Findings in a Case of Acute Macular Neuroretinopathy Accompanied by Behçet Disease.

Purpose: To report a case of acute macular neuroretinopathy (AMN) in Behçet Disease.Case: A 23-year-old male presented with a complaint for central scotoma in his right eye. He had been diagnosed with Behçet Disease 3 years ago. Best-corrected visual acuity (BCVA) was 20/20. Anterior chamber and fundus examinations were unremarkable. Optical coherence tomography revealed a paracentral area of outer nuclear layer thinning. Infrared reflectance showed a well-defined, circular, hyporeflective area. Optical coherence tomography angiography revealed an area of capillary dropout in deep retinal capillary plexus corresponding to that hyporeflective lesion. Microperimetry test showed decreased macular sensitivity on the lesion area and the loss of the macular integrity. In multifocal electroretinogram, diminished amplitudes of the central cone responses were detected nasal to fixation.Conclusion: Behçet disease is a cause of occlusive retinal vasculitis. Accompanied retinal microvascular disease may be a possible risk factor of AMN suggesting ischemic etiopathogenesis for AMN.

Resurgence of ocular syphilis in British Columbia between 2013-2016: a retrospective chart review.

OBJECTIVE: To characterize the trends and explore the demographics, ophthalmic manifestations, and outcomes of ocular syphilis cases in British Columbia. DESIGN: Retrospective chart review. PARTICIPANTS: Ocular syphilis cases reported to the British Columbia Centre for Disease Control (BCCDC) between January 2013 and December 2016. METHODS: The demographic and clinical data were extracted from the BCCDC's centralized sexually transmitted infection database and the ophthalmologists' clinical charts. RESULTS: There was a steady increase in the rate of syphilis infection per 100 000 population, from 3.4 in 2010 to 18.4 in 2018. There were 39 ocular syphilis cases identified from January 2013 to December 2016. The median age was 50 years (interquartile range: 40-59.5 years); 82.1% were male and 51.3% were HIV positive. The clinical charts belonging to 32 patients were available for review, 14 of which (43.8%) presented with bilateral ocular complaints (46 affected eyes). The most commonly noted ocular presentations were uveitis (93.5%), including retinal vasculitis in 54.3%, and optic nerve involvement in 65.2% (which included papillitis, optic nerve swelling, or pallor). Panuveitis was the most frequent type of uveitis (52.2% of all eyes); 77.8% of affected eyes with best-corrected visual acuity (BCVA) ≤20/50 on presentation had an improvement of 2 or more Snellen lines of visual acuity at their final assessment. At presentation, 37.0% of eyes had BCVA ≤20/200, which decreased to 17.1% at final assessment. CONCLUSION: Ocular syphilis, although rare, is on the rise globally and can result in serious ocular sequelae. A high index of suspicion is required for proper diagnosis and treatment.

A Long-Term Follow-up of Retinal Vasculitis - Do They Develop Systemic Disease?

Purpose: To study systemic association and relapses in a long-term follow-up of primary retinal vasculitis (PRV) and possible tubercular vasculitis (PTV) cases. Method: Retrospective, descriptive chart review of patients diagnosed as PRV and PTV with ≥1-year follow-up. Clinical presentation, systemic association, morphology of vasculitis, relapses, and treatment were noted. Results: 123 eyes of 76 patients were studied. Occlusive (n = 97), exudative (n = 16), combined (n = 10) and focal (n = 7) vasculitis were seen. Vitreous hemorrhage at presentation was noted in 27% eyes (n = 33). Four patients (3.25%) developed systemic disease during follow-up (2 psoriasis, 1 Systemic Lupus Erythematosus, 1 ulcerative colitis). Mean number of cases with relapses were 45 (59.21%). Number of cases with relapses in PRV and PTV were 20 (66.66%) and 16 (66.66%), respectively. (p = 1) Conclusion: Systemic disease attributed to vasculitis can rarely develop during follow up of PRV and PTV patients. Relapses remain almost same in PTV and PRV.

Novel findings in enhanced S-cone syndrome: a case with macular retinal neovascularization and severe retinal vasculitis.

PURPOSE: To describe a novel association of enhanced S-cone syndrome (ESCS) with macular retinal neovascularization and severe retinal vasculitis. METHODS: Clinical examination, spectral domain optical coherence tomography, fluorescein angiography, fundus autofluorescence, infrared reflectance and electroretinography were used to study a 25-year-old male with a history of night blindness from early childhood and recent accelerated visual loss in right eye. RESULTS: Pigmented lesions were observed along the arcades without peripheral retinal involvement. Intraretinal cystoid spaces, retinal neovascularization of posterior pole and severe peripheral and posterior retinal vasculitis were found on clinical examination and multimodal imaging. Based on characteristic clinical and electroretinographic findings, a diagnosis of ESCS was made. CONCLUSION: This case highlights novel associations of retinal neovascularization and vasculitis with ESCS.

Vascular Inflammation Risk Factors in Retinal Disease.

Inflammation of the blood vessels that serve the central nervous system has been increasingly identified as an early and possibly initiating event among neurodegenerative conditions such as Alzheimer's disease and related dementias. However, the causal relevance of vascular inflammation to major retinal degenerative diseases is unresolved. Here, we describe how genetics, aging-associated changes, and environmental factors contribute to vascular inflammation in age-related macular degeneration, diabetic retinopathy, and glaucoma. We highlight the importance of mouse models in studying the underlying mechanisms and possible treatments for these diseases. We conclude that data support vascular inflammation playing a central if not primary role in retinal degenerative diseases, and this association should be a focus of future research.

Ocular Manifestations and Visual Outcomes of Behçet's Uveitis in a Thai population.

PURPOSE: To report on ocular manifestations and visual outcomes of Thai patients with Behçet's Uveitis (BU). METHODS: We reviewed medical records of 50 BU patients (31 males and 19 females). Ocular manifestations, treatment modalities, complications, and visual outcomes were registered. RESULTS: Ocular involvement was bilateral in 76% of patients, resulting in 89 affected eyes. Panuveitis and posterior uveitis were the most common types. Retinal vasculitis was noted in majority of affected eyes and specifically arteritis was noticed in 32/57(56%). Most patients received combination therapy of systemic corticosteroids and immunosuppressive agents (azathioprine 72%). At final visit, VA ≤20/200 was observed in 25 affected eyes (28%). Risk factors for poor visual outcome were poor visual acuity at presentation (p < 0.001) and development of optic atrophy (p = 0.01). CONCLUSIONS: Typical ocular manifestations of Thai patients with BU consisted of bilateral uveitis affecting posterior eye segment with high rate of complications and frequent visual loss.

Clinical Characteristics and Prognostic Factors in Ankylosing Spondylitis Associated Uveitis.

PURPOSE: To identify the clinical features and prognostic factors of uveitis associated with ankylosing spondylitis (AS). METHODS: This retrospective, interventional case series study reviewed the medical records of 91 AS patients with uveitis. RESULTS: The characteristics of AS-associated uveitis included male preponderance (70%), average onset in the fourth decade, unilateral manifestation (87.9%), and vitreous involvement or retinal vascular leakage (36.3%). All patients had acute anterior uveitis. The best corrected visual acuity in logMAR improved from 0.8 ± 0.3 to 0.1 ± 0.2. The use of biologic agents was the only significant factor in the multivariate analysis. Patients with vitreous involvement/retinal vascular leakage were more likely to use systemic/peribulbar steroids for inflammation control, and achieved equally favorable visual outcome as in those without vitreous involvement/retinal vascular leakage. CONCLUSION: The clinical characteristics and profile of visual prognostic factors suggest an association between the severity of ocular inflammation and systemic disease.

Varicella-zoster virus necrotising retinitis, retinal vasculitis and panuveitis following uncomplicated chickenpox in an immunocompetent child.

A 4-year-old girl presented with acute left visual loss 4 weeks after uneventful chickenpox. She was found to have left necrotising retinitis and profound retinal vasculitis and vitritis. Aqueous humour was PCR positive for varicella-zoster virus. Combined intravenous and intravitreal antiviral treatment led to rapid improvement with settled retinitis, no vascular occlusion and good recovery of vision. Her recent coinfection with Epstein-Barr virus may have acted to provoke the retinitis.

Epidemiology and clinical features of inflammatory retinal vascular occlusions: pooled data from two tertiary-referral institutions.

IMPORTANCE: In a subset of patients with retinal vasculitis, there is occlusion of blood flow through the retinal vessels. These eyes are at high risk of sight-threatening complications. BACKGROUND: To characterize epidemiology, clinical course, treatment and outcomes of occlusive retinal vasculitis (ORV). DESIGN: Retrospective study PARTICIPANTS: Seventy-seven uveitis patients with ORV at two large tertiary-care institutions (the USA and India). METHODS: Out of 2438 patients screened, 346 patients were diagnosed with retinal vasculitis of which 77 patients (96 eyes) were diagnosed with ORV. Patients with ORV (capillary, arteriolar and/or venular) were further analysed. Diagnostic criteria for occlusive vasculitis included (i) absence of blood flow in vessels (arterioles, venules and/or capillaries), (ii) capillary non-perfusion areas and/or arteriolar-venous anastomosis and (iii) intraretinal haemorrhages, cotton-wool spots or vitreous haemorrhage. MAIN OUTCOME MEASURES: Best-corrected visual acuity, treatment and complications. RESULTS: The mean age was 32.09 ± 13.51 years. Most common aetiologies were tuberculosis and Adamantiades-Behçet's disease in India and systemic lupus erythematosus in the USA. Best-corrected visual acuity improved from 0.38 ± 0.30 logMAR (20/48 Snellen equivalent) (baseline) to 0.25 ± 0.30 (20/35 Snellen equivalent) at final visit (P < 0.0001). Vitreous haemorrhage was seen in 31.08% eyes. Pars plana vitrectomy was performed in 12.16% eyes. Therapy with systemic steroids was required in 78.48% patients. In addition, 46.75% patients required immunomodulators and/or biologics. CONCLUSIONS: Occlusive retinal vasculitis is caused by heterogeneous group of uveitides depending upon the geographic location. It is imperative to identify eyes with ORV as they are predisposed to complications requiring aggressive therapy.

Review of people with retinal vasculitis and positive QuantiFERON®-TB Gold test in an area nonendemic for tuberculosis.

PURPOSE: To assess the frequency of a positive QuantiFERON®-TB Gold test (quantiferon) among patients with retinal vasculitis in an area nonendemic for tuberculosis (TB); to review clinical characteristics and management of affected individuals. METHODS: Consecutive patients with retinal vasculitis and a positive quantiferon were retrospectively analyzed. Demographics, clinical data, laboratory, imaging findings, and therapy were evaluated. RESULTS: Among 49 patients with retinal vasculitis, 12 (24%) had a positive quantiferon. Median age was 37 years, there were five female patients. Five individuals (42%) had previously lived in a country endemic for TB. Retinal vasculitis was occlusive in six patients (50%). On chest imaging, pulmonary tuberculosis was suspected in one patient (8.3%). Treatment modalities included full antitubercular treatment (n = 1), isoniazid prophylaxis (n = 6), systemic corticosteroids (n = 8), and laser treatment (n = 5). After a median follow-up of 27.5 months, inflammation was inactive (n = 6) or recurrently present (n = 6). No patient lost ≥ 2 lines of best-corrected visual acuity during follow-up. CONCLUSIONS: The quantiferon test is recommended in the evaluation of people with retinal vasculitis. Interpretation of a positive result can be challenging in a country nonendemic for TB. The majority of patients with quantiferon-positive retinal vasculitis were found to have latent TB.

Characteristics and Visual Outcome of Refractory Retinal Vasculitis Associated With Antineutrophil Cytoplasm Antibody-Associated Vasculitides.

PURPOSE: To describe the clinical characteristics, therapies, visual outcomes, and prognoses of patients with retinal vasculitis associated with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). DESIGN: Retrospective case series. METHODS: Patients diagnosed with retinal vasculitis associated with AAV and at least 6 months of follow-up were included. Demographic data, systemic and ocular features, best-corrected visual acuity at the initial visit and latest visit, fluorescein angiography (FA) and indocyanine green angiography (ICGA) findings, therapy regimen, and outcome were collected from the Massachusetts Eye Research and Surgery Institution (MERSI) database from 2006 to 2017. RESULTS: Fourteen patients (22 eyes) were identified. Twelve had granulomatosis with polyangiitis (GPA) and 1 each had microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). FA showed that AAV affected small-to-medium-size retinal vessels. Seven cases (50%) had both vein/venule and artery/arteriole involvement. Four cases co-presented with choroidal vasculitis. All of them failed various immunomodulatory therapies prior to referral to MERSI. Six patients received rituximab plus prednisone as their final therapy and 5 of them achieved remission. Four patients who failed cyclophosphamide previously were induced into remission by rituximab. Patients were followed for 33.4 ± 25.5 (range 6-84) months. Nine of 14 patients (64.3%) achieved remission at their latest visit. Seventeen of 22 eyes (77.3%) met the criteria for a good (≥20/40) visual outcome. CONCLUSION: The majority of patients enjoyed a good visual outcome and achieved remission after aggressive treatment. Rituximab should be considered as an initial treatment for patients with refractory retinal vasculitis associated with AAV.

FROSTED BRANCH ANGIITIS IN METHIMAZOLE-INDUCED ANTINEUTROPHIL CYTOPLASMIC ANTIBODY-POSITIVE VASCULITIS.

PURPOSE: To describe an unusual case of frosted branch angiitis that developed in a patient with acute onset systemic vasculitis possibly triggered by the antithyroid medication methimazole. METHODS: We conducted a thorough review of the medical records of a 16-year-old female patient who presented with frosted branch angiitis. During the initial hospital admission, the patient underwent an extensive systemic workup to determine the etiology of her disease and ophthalmologic testing including fundus photographs and fluorescein angiography. RESULTS: Our patient presented with a unilateral acute onset loss of vision, whose fundus examination revealed the pathognomonic features of frosted branch angiitis. Extensive systemic workup revealed an antineutrophilic cytoplasmic antibody-positive vasculitis, possibly triggered by methimazole. CONCLUSION: This case is the first reported frosted branch angiitis associated with a drug-induced antineutrophilic cytoplasmic antibody-positive vasculitis triggered by methimazole.

Long-Term Outcomes of a Large Cohort of Patients with Eales' Disease.

PURPOSE: To analyze the long-term visual outcomes of Eales' patients. METHODS: A retrospective review of Eales' patients diagnosed between 1985 and 1995 with >10 years follow-up done. RESULTS: We included 500 patients (898 eyes) with mean follow-up duration of 15.8 years (10-25 years), and 81% patients had bilateral disease. Patients using oral steroid during acute stage disease had significantly better visual outcome at the final visit [0.42 logMar(6/18) ± 0.723 logMar(6/30)] compared to patients who did not receive oral steroids [(0.5907 logMar(6/24) ± 0.945 logMar(6/48)] (p = 0.004). Patients who received laser therapy had significantly better visual outcome at the final visit [(0.415 logMar(6/18) ± 0.66 logMar(6/30)] compared to those who did not undergo laser treatment [(0.9237 logMar(6/48) ± 1.31 logMar(6/120)] (p < 0.001). Poor presenting visual acuity and late stage of presentation were associated with poor visual outcome. Fifty-two percent of eyes had <5 recurrences over 10 years. CONCLUSION: Eales' disease is a bilateral recurrent retinal vasculitis disorder and timely treatment with steroid and/or laser photocoagulation result in better visual outcomes.