Outcomes in Patients with Vogt-Koyanagi-Harada Disease from the First-line Antimetabolites for Steroid-sparing Treatment Uveitis Trial.

PURPOSE: To compare the effectiveness of methotrexate (MTX) and mycophenolate mofetil (MMF) in achieving corticosteroid-sparing control of uveitis in patients with Vogt-Koyanagi-Harada (VKH) disease. METHODS: A subanalysis of patients with VKH from the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial, a randomized, observer-masked, comparative effectiveness trial, with comparisons by treatment (MTX versus MMF) and disease stage (acute versus chronic). Individuals with noninfectious uveitis were placed on a standardized corticosteroid taper and block randomized 1:1 to either 25mg weekly oral MTX or 1.5g twice daily oral MMF. The primary outcome was treatment success defined by corticosteroid-sparing control of uveitis at 6 months. Additional outcomes included change in best spectacle-corrected visual acuity (BSCVA), retinal central subfield thickness (CST), and resolution of serous retinal detachment (SRD). RESULTS: Ninety-three out of 216 enrolled patients had VKH; 49 patients were randomized to MTX and 44 to MMF, of which 85 patients (46 on MTX, 39 on MMF) contributed to the primary outcome. There was no significant difference in treatment success by antimetabolite (80.4% for MTX compared to 64.1% for MMF; P=.12) or in BSCVA improvement (P=.78). Methotrexate was superior to MMF in reducing CST (P=.003) and resolving SRD (P=.02). There was no significant difference in treatment success by disease stage (P=.25), but patients with acute VKH had greater improvement in BSCVA (P<.001) and reduction of CST (P=.02) than chronic VKH patients. CONCLUSIONS: MTX and MMF have comparable outcomes as corticosteroid-sparing immunosuppressive therapies for VKH. Visual acuity improvement was greater in acute vs chronic VKH. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00182929.

Risk of failing both methotrexate and mycophenolate mofetil from the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial.

BACKGROUND: The antimetabolites methotrexate (MTX) and mycophenolate mofetil (MMF) are commonly used as initial corticosteroid-sparing treatment for uveitis. There is little data examining risk factors for failing both MTX and MMF. The objective of this study is to determine risk factors for failing both MTX and MMF in patients with non-infectious uveitis. MAIN BODY: This is a sub-analysis of the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial, which was an international, multicenter, block-randomized, observer-masked, comparative effectiveness trial comparing MTX and MMF as initial treatments for non-infectious uveitis. This study was undertaken at multiple referral centers in India, the United States, Australia, Saudi Arabia and Mexico between 2013 and 2017. A total of 137 patients who completed all 12 months of follow-up from the FAST trial, were included in this study. The primary outcome was failing both antimetabolites over the 12 months of the trial. Potential predictors included: age, sex, bilateral involvement, anatomic location of the uveitis, presence of cystoid macular edema (CME) and retinal vasculitis at baseline visit, uveitis duration, and country/study sites as risk factors for failing both MTX and MMF. The presence of retinal vasculitis posterior to the equator on fluorescein angiogram was associated with failing both MTX and MMF. CONCLUSION: Retinal vasculitis may be a risk factor for failing multiple antimetabolites. Clinicians could consider more quickly advancing these patients to other medication classes, such as biologics.

Risk factors for subretinal fibrosis in patients with Vogt Koyanagi Harada syndrome.

PURPOSE: To identify the risk factors for the development of subretinal fibrosis (SRF) among patients with Vogt-Koyanagi-Harada (VKH) syndrome. METHODS: In this case-control study, electronic clinical records from patients diagnosed with VKH syndrome who attended the Inflammatory Eye Disease Clinic at a tertiary care ophthalmology reference center were assessed to identify risk factors from demographic, clinical, and epidemiological variables. Cases were defined as SRF and VKH, whereas the controls were VKH patients without SRF. RESULTS: A total of 150 electronic charts were reviewed, 92 patients with a follow-up longer than 12 months were included; 39 cases and 53 controls. A multivariate analysis found bullous serous retinal detachment as a significant risk factor for SRF (adjusted OR 8.93, 95% CI 1.94-41.1). CONCLUSION: Patients with VKH syndrome who develop a bullous retinal detachment have an 8 times higher risk of developing SRF in the long term.

Alternaria chartarum sclerokeratouveitis: A new fungus cause.

We report a case of Alternaria chartarum sclerokeratouveitis with an unfavorable response to treatment. To the best of our knowledge, there are no previous reports of this fungus invading the sclera. A 68-year-old diabetic farmer male patient presented with a 3-week history of pain and redness and a decrease in visual acuity occurring 5 days before admittance in the right eye. Examination revealed severe mixed hyperemia and a scleral calcified plaque with a surrounding area of ischemia and lysis. The cornea showed diffuse infiltrates, stromal edema, and hypopyon. Initial scrapings were negative, and empiric antibiotics were started. After a fungus was reported, topical and systemic antifungals were initiated, but there was no clinical response. The eye was enucleated. A slow-growing fungus A. chartarum, resistant to voriconazole, was isolated. Fungal etiology must be kept in mind when dealing with infectious scleritis. Despite treatment, the outcome of this case was unfavorable due to the slow-growing nature of the fungus and this strain's resistance to voriconazole.

Association of retinal detachment with age 50 years or younger at onset in patients with acute retinal necrosis.

BACKGROUND: Due to the guarded prognosis of acute retinal necrosis (ARN), it is relevant to develop a strategy to early categorize those patients in a higher risk of worse outcomes. The purpose of this study is to describe clinical features and predictive factors for retinal detachment (RD) in patients with ARN. METHODS: Retrospective observational case series of 34 adult patients (38 eyes) with ARN examined between January 2005 and July 2015 in the National Eye Institute (Bethesda, USA), the Department of Ophthalmology, University of Chile (Santiago, Chile), and APEC (CDMX, Mexico). RESULTS: A total of 16 males and 18 females with a mean age at presentation of 44.5 ± 16.8 years were included. Twenty-seven patients (79.4%) received intravenous acyclovir as first-line treatment, and 7 patients received either oral antiviral (4 patients) or oral plus intravitreal antiviral (3 patients). All subjects were treated with prednisone, with a mean initial dose of 57.7 ± 16.3 mg per day. Seventeen patients (50.0%) developed retinal detachment. An association of retinal detachment with age at onset was observed (p = 0.04), with patients younger than 50 years presenting a higher risk (OR = 14.86, p = 0.0009). Additionally, patients in this higher risk group had more inflammation in both anterior chamber and vitreous (p = 0.04 and 0.03, respectively). No other predictive factor for retinal detachment was found in the present study. CONCLUSIONS: RD represents an important complication in patients with ARN. Younger patients may be at higher risk of this complication, possibly secondary to the presence of a higher level of inflammation.

Initial-onset acute and chronic recurrent stages are two distinctive courses of Vogt-Koyanagi-Harada disease.

PURPOSE: To describe distinctive stages of Vogt-Koyanagi-Harada (VKH) disease: initial-onset acute versus chronic recurrent disease. METHODS: A comprehensive literature review regarding stages and clinical presentations of VKH disease was conducted. RESULTS: Despite a list of signs that has been described as characteristic features of early or late phases of VKH disease, the current classification -developed by an international committee and published in 2001- does not consider a distinction regarding the time from onset of disease symptoms, and specific findings observed at certain time point from the symptoms presentation and outcomes related to the stage of VKH disease. In that sense, chronic recurrent VKH disease is more refractory to treatment and is associated with a higher rate of complications. Accordingly, this subset of VKH patients has poorer functional and anatomical outcomes than patients with an initial-onset acute disease. CONCLUSIONS: An early clear distinction of VKH phenotype [Initial-onset acute versus chronic recurrent disease] should be considered in each clinical scenario, evaluating the delay in diagnosis and the clinical presentation, since it may help clinicians to perform a correct disease prognosis categorization and thus to make treatment decisions in terms of potential refractoriness or expected clinical outcomes.

Characterization of cyclitic membranes by ultrabiomicroscopy in patients with pars planitis.

BACKGROUND: In previous studies, authors use ultrasound biomicroscopy (UBM) to analyze the characteristics of cyclitic membranes and the associated complications in patients with pars planitis. However, there are no reports regarding the prevalence of cyclitic membranes or complications at diagnosis and during follow-up. PURPOSE: To describe the characteristics and complications of cyclitic membranes, as determined by UBM in patients with pars planitis using AVISO-S™ (Quantel Medical) equipment with a 50-MHz linear probe with a focus at the pars plana. DESIGN: This retrospective study reviewed UBM images of patients diagnosed with pars planitis, from the Inflammatory Eye Disease Clinic in Mexico City from January 2010 to June 2016. RESULTS: Cyclitic membranes were observed in the first UBM image in 67 eyes (56.7%) and during follow-up in 81 eyes (68.62%). In 67 eyes (82.71%), the cyclitic membranes extended through one or two quadrants. Extension toward the posterior lens capsule was recognized in 15 eyes (18.52%) and extension toward the peripheral retina in 12 eyes (14.81%). Complications included ciliary body detachments in 10 eyes (12.35%) and peripheral retinal traction in 8 eyes (9.88%). CONCLUSIONS: UBM is a valuable tool for the diagnosis of cyclitic membranes at admittance and during follow-up of patients with pars planitis; it helps the clinician to detect this complication early.

Ultrabiomicroscopic Findings in Acute Uveitic, Convalescent and Chronic Recurrent Stage of Vogt-Koyanagi-Harada Syndrome.

PURPOSE: To describe the ultrabiomicroscopy (UBM) characteristics in patients with uveitic, convalescent, and recurrent Vogt-Koyanagi-Harada (VKH) disease. METHODS: In this prospective, non-interventional, and observational study, all UBM variables, namely pars plicata and pars plana thickness, ciliochoroidal detachment, angle chamber, anterior chamber depth, ID2, and presence of ciliary processes, were compared between acute uveitic, convalescent, and chronic-recurrent phases. RESULTS: Ninety-one eyes were analyzed. Ciliochoroidal detachment (20%) and unclear ciliary processes (15%) are the most characteristic findings of the uveitic phase. At 1 and 3 months, ciliochoroidal detachment is no longer observed. In recurrent phase, pars plicata and pars plana thickness increases again and then decreases after the first month of treatment. Convalescent-phase does not show significant differences in UBM variables after a 6-month follow up. CONCLUSIONS: UBM may have a role in evaluating response to treatment in uveitic and recurrent phases and in the early detection of recurrences.

Echographic findings in the late stages of Vogt-Koyanagi-Harada disease in mexican population / Resultados ecográficos nas fases atrasadas da doença de Vogt-Koyanagi-Harada na população mexicana

Purpose: To correlate clinical findings of Vogt-Koyanagi-Harada disease with standardized echography findings in a cross-sectional, descriptive and observational study. Methods: Patients with Vogt-Koyanagi-Harada disease in the convalescent and recurrence phases were evaluated with standardized ocular echography. Eyes with opaque media were excluded. Clinical findings were correlated with echographic data. Results: Thirty-seven eyes of 25 patients were included. Best corrected visual acuity was in average 20/100 (0.70 logMAR). Clinical findings included: sunset glow fundus (92%), pigment migration (92%), nummular chorioretinal depigmented scars (68%) and subretinal fibrosis (64.8%). Standardized echography was able to recognize all the cases with subretinal fibrosis (n=24) described clinically. Standardized echography showed a 100% sensitivity and specificity of finding subretinal fibrosis. Subretinal fibrosis in patients with Vogt-Koyanagi-Harada represents a risk factor for low vision. In our patients’ eyes, presence of subretinal fibrosis had a 2.5 time relative risk of having a visual acuity equal or worst to 20/70. Conclusions: Standardized echography represents a useful tool in patients with VKH in the chronic (convalescence and recurrence) phase of the disease. Subretinal fibrosis, a sight threatening complication in the convalescence and recurrent phases of Vogt-Koyanagi-Harada, can be diagnosed with ocular echography, with characteristic images. Knowledge of these images can be useful in cases with opaque media and bilateral anterior segment granulomatous inflammatory disease. .

Objetivo: Correlacionar achados clínicos da síndrome de Vogt-Koyanagi-Harada com resultados ecográficos padronizado da doença em um estudo transversal, descritivo e observacional. Métodos: Pacientes com a doença de Vogt-Koyanagi-Harada, o convalescente e recorrência em fases padronizadas foram avaliados com ecografia ocular. Olhos com material opaco foram excluídos. Achados clínicos foram correlacionados com dados ecográficos. Resultados: Um total de 25 pacientes e trinta e sete olhos foram incluídos no estudo. A acuidade visual (AV) 20/100 foi em média 0.70 logMAR. Os achados clínicos incluídos: sunset glow fundus (92%), pigmento migração (92%), numular despigmentado cicatrizes coriorretinianas (68%) e fibrose sub-retiniana (64,8%). A ecografia padronizada foi capaz de reconhecer todos os casos de fibrose sub-retiniana (n= 24) descrito clinicamente. A ecografia revelou um padrão 100% de sensibilidade e especificidade do diagnóstico fibrose sub-retiniana. Sub-retiniana em pacientes com fibrose Vogt-Koyanagi-Harada representa um fator de risco para a baixa visão. Em nossos pacientes olhos, presença de fibrose subretiniana tinham um risco relativo 2,5 hora de ter uma acuidade visual igual ou pior para 20/70. Conclusão: Ecografia padronizadarepresenta uma ferramenta útil em pacientes portadores da doença na fase crônica (convalescença, e recidiva). Fibrose sub-retiniana, uma visão ameaçadora e complicação na convalescença e recorrentes nas fases da Síndrome de Vogt-Koyanagi- Harada, podem ser diagnosticados com ecografia ocular, com imagens características. O conhecimento dessas imagens pode ser útil em casos com material opaco e segmento anterior bilateral da doença inflamatória granulomatosa. .

Manifestaciones oculares de las vasculitis primarias sistémicas / Ocular manifestations of primary systemic vasculitis

Las vasculitis primarias (VP) pueden cursar con diversas manifestaciones oculares y estas pueden ser las únicas al inicio de la enfermedad. La afección ocular es común en las VP y potencialmente conduce a morbilidad significativa, incluyendo pérdida de la visión. El diagnóstico y tratamiento tempranos mejoran el pronóstico visual. El abordaje terapéutico constituye un reto y debe ser multidisciplinario. El tratamiento de las manifestaciones oculares corresponde al de la enfermedad de base. La primera línea de tratamiento son los corticoesteroides sistémicos, generalmente combinados con fármacos inmunomoduladores, que fungen también como ahorradores de glucocorticoides. Existen nuevos tratamientos, como los agentes biológicos, que parecen prometedores para las alteraciones oculares de las VP (AU)

A variety of ophthalmic manifestations can occur in patients who have systemic vasculitides and may be the presenting feature. Ocular involvement is frequently found and can result in significant morbidity, even in blindness. Early diagnosis and treatment may improve visual outcome. The management is challenging and requires a multidisciplinary approach. Treatment of ocular manifestations and systemic disease usually follows the same path. The mainstay of treatment is the use of systemic corticosteroids, usually combined with steroid-sparing immunosuppressive drugs. New, promising, emerging therapies rely on the development of biologic agents, which seem useful in the ocular manifestations of systemic vasculitides (AU)

[Ocular manifestations of primary systemic vasculitis]. / Manifestaciones oculares de las vasculitis primarias sistémicas.

A variety of ophthalmic manifestations can occur in patients who have systemic vasculitides and may be the presenting feature. Ocular involvement is frequently found and can result in significant morbidity, even in blindness. Early diagnosis and treatment may improve visual outcome. The management is challenging and requires a multidisciplinary approach. Treatment of ocular manifestations and systemic disease usually follows the same path. The mainstay of treatment is the use of systemic corticosteroids, usually combined with steroid-sparing immunosuppressive drugs. New, promising, emerging therapies rely on the development of biologic agents, which seem useful in the ocular manifestations of systemic vasculitides.

Lupus relapse presented as frosted branch retinal angiitis: case report.

PURPOSE: To describe a systemic lupus erythematosus (SLE) relapse, which presented as frosted branch retinal angiitis. DESIGN: Clinical case report. METHODS: A 16-year-old female patient had an SLE relapse that appeared as frosted branch angiitis while being treated with deflazacort and azathioprine. RESULTS: Complete resolution of the vasculitis was achieved with a 3-day course of pulsed intravenous methylprednisolone and oral prednisone 3 weeks later. CONCLUSIONS: Even with proper immunosuppressive treatment, SLE can relapse. This case presented as frosted branch retinal angiitis, which is a clinical picture that is rarely described in SLE.

Corneal ectasia secondary to peripheral endotheliopathy in a patient with classic pars planitis.

PURPOSE: To report a case of corneal ectasia secondary to pars planitis corneal endotheliopathy METHODS: Clinical case description and proposed hypothesis regarding development of corneal ectasia RESULTS: Eight-year-old male presented with 360° peripheral corneal endotheliopathy and edema, granulomatous keratic precipitates, and mild iritis OD. A progressive corneal ectasia then developed. Twenty months later, OS presented similarly and anterior chamber inflammatory cells, vitreous snowballs, and retinal vasculitis were observed OU. Classic pars planitis was diagnosed CONCLUSION: This is the first case of endotheliopathy as the first manifestation of pars planitis and as a cause of a secondary central cornea ectasia developed.

Familial case of Blau syndrome associated with a CARD15/NOD2 mutation.

PURPOSE: Blau syndrome is a rare autosomal dominant disorder characterized by early onset granulomatous arthritis, uveitis, skin rash and camptodactyly. We report a familial case of Blau syndrome associated with a CARD15/NOD2 mutation. METHODS: PCR amplification and automated DNA sequencing of the complete CARD15/NOD2 coding sequence was performed. RESULTS: Molecular analysis in affected subjects disclosed a heterozygous c.1147G>C point mutation in CARD15/NOD2 exon 4, that predicts a p.E383K change at the protein level. CONCLUSIONS: Blau syndrome should be considered in the differential diagnosis of childhood uveitis and the genetic analysis of the CARD15/NOD2 gene is helpful in the diagnosis.