Search

STAMP (System-Theoretic Accident Model and Processes) techniques such as STPA (System- Theoretic Process Analysis) and STPA-Sec (STPA for Security) have been applied only in an adhoc manner, without the aid of tools. More recently, tools have been proposed to help the application of STPA and STPA-Sec. Most of the tools focus on user experience issues and do not cover all the aspects of STPA and STPA-Sec. Three aspects of tools are systematization, automation and analysis completeness. Systematization allows the analysis to be performed in a more disciplined way while automation allows a more time efficient analysis. Analysis’ completeness is the analysis coverage in a given domain. We identify the essential requirements supporting business and stakeholders' needs for a STAMP based tool. We propose a STAMPcompliant web application, named WebSTAMP, for STPA and STPA-Sec. WebSTAMP is intended to aid analysts throughout the analysis process in a more automated and comprehensive way, and it aims to be a collaborative tool. We illustrate how the requirements are implemented in the current version of WebSTAMP with an example of use. The results show that WebSTAMP assists analysts to conduct safety and security analyses in a more systematic, automated and comprehensive manner.

Purpose: To present paradoxical reaction (PR) in three cases with ocular tuberculosis (OTB) treated with antitubercular therapy (ATT), highlighting diagnostic challenges and treatment strategies., Methods: We retrospectively reviewed clinical records of three OTB patients presenting with paradoxical worsening after ATT initiation at two Brazilian university hospitals., Results: The patients (2 males, 1 female) experienced worsening clinical presentation (increased inflammation, vision loss) within two to three weeks after initiating ATT. One patient who was HIV-positive with unilateral multifocal choroiditis developed PR soon after starting antiretroviral therapy. The second patient presented with a choroidal tuberculoma in both eyes. The third patient also had multifocal choroiditis and developed a localized choroidal elevation with a double-layer sign as a manifestation of PR. All patients were maintained on ATT therapy in association with corticosteroids and experienced improvement of inflammatory signs., Conclusion: This case series highlights the potential for PR in OTB patients. Close monitoring and prompt therapeutic adjustments are crucial for management success.

Unvaccinated identical twins developed bilateral anterior uveitis soon after the onset of coronavirus disease 2019 symptoms. During follow-up, both patients developed choroiditis, and one twine developed posterior scleritis and serous retinal detachment. Prompt treatment with oral prednisone ameliorated the lesions, and no recurrence was observed at the 18-month follow-up. Choroiditis may rarely be associated with severe acute respiratory syndrome coronavirus 2 infection, and it responds well to corticosteroid therapy. Although the exact mechanism is unknown, we hypothesize that the virus may act as an immunological trigger for choroiditis.

Aims: To investigate the changes in quality-of-life (QoL) metrics at a 24-month interval in non-acute VKHD patients and their association with inflammation, treatment, and visual function., Methods: SF-36 and VFQ-25 questionnaires were administered at two 24-month-apart moments to 22 non-acute VKHD patients followed for ≥12 months since acute disease onset. "Improvement," "unchanged," or "worsening" in questionnaires scores (difference >5-point) between M1 and M2 and their associations were sought., Results: Absence of systemic treatment or optic disc hyperfluorescence was associated with improved general health (SF-36). Improvement in binocular contrast sensitivity resulted in better ocular pain score; absence of anterior uveitis relapse, stable fundus findings, no use of cyclosporine or no intravitreal injections resulted in unchanged/better dependency score; no intravitreal injections resulted in unchanged/better mental health score (VFQ-25)., Conclusion: Stability/improvement in QoL scores was associated with controlled inflammation, better visual function, and no need for treatment. Subclinical inflammatory signs did not impact QoL scores.

Purpose: To evaluate the parafoveal macular microvasculature and the macular function in patients with retinal vasculitis associated with Behçet's uveitis., Methods: In 14 patients with inactive Behçet's uveitis and 26 control individuals (13 with nonocular Behçet's syndrome and 13 healthy subjects), we analyzed the retinal nerve fiber layer, ganglion cell layer, full retinal thickness, foveal avascular zone area and sectorial parafoveal vascular density in the superficial vascular plexus, intermediate capillary plexus, and deep capillary plexus using SPECTRALIS optical coherence tomography (OCT) 2 and OCT angiography. Macular sensitivity was analyzed using an MP-3 microperimeter., Results: Eighteen eyes (78%) had a best-corrected visual acuity ≥ 20/25. Significant differences were found in Behçet's uveitis in comparison with the controls on the OCT and OCT angiography: 14.8%, 22.4%, and 14.9% ganglion cell layer thinning in the global, nasal, and inferior sectors, respectively; 6%, 13.2%, and 7.5% full retinal thickness thinning in the superior, nasal, and inferior sectors; and 16.8%, 14.9%, 23.6%, 15.8%, and 12.6% mean deep capillary plexus density reduction in the global, superior, nasal, inferior, and temporal sectors. Microperimetry data demonstrated significant mean reductions of 21% and 23.6% in central and average macular sensitivities and 28.8%, 40.4%, 27.7%, and 24.2% in the superior, nasal, inferior, and temporal sectors, respectively. Outer plexiform layer elevations were observed in Behçet's uveitis (69.6%)., Conclusion: Behçet's uveitis presented structural and functional macular damage despite good best-corrected visual acuity, mainly affecting the nasal sector and the deep capillary plexus. On OCT and OCT angiography, quantitative and qualitative changes can be valuable biomarkers of ocular involvement in Behçet's syndrome.

Background: The tomographic finding, which has been called the "fingerprint sign" in en face reconstructions, seems to be the result of a variety of processes that cause distension of the outer plexiform layer (OPL) and the Henle fiber layer (HFL). The aim of this paper is to describe the appearance of concentric rings at the OPL/HFL interface visualized using en face reconstructions of cross-sectional optical coherence tomography images of patients with Vogt-Koyanagi-Harada disease., Methods: Retrospective analysis of images of six eyes of three patients obtained by cross-sectional OCT imaging and en face reconstruction at the level of the OPL/HFL interface., Results: All eyes presented with a dentate or saw-tooth pattern of the OPL/HFL interface on cross-sectional OCT with corresponding concentric rings on en face OCT reconstruction, consistent with the recently published "fingerprint sign". Initial OPL/HFL interface changes were observed between the first and fourth months after treatment and resolution of VKHD associated serous retinal detachments. These OPL/HFL interface changes have persisted for many years following the resolution of the active inflammation., Conclusions: Changes in the OPL/HFL interface can be identified following successful treatment of VKHD. These included both a dentate or saw-tooth pattern on cross-sectional imaging and concentric rings or the "fingerprint sign" on en face reconstructions. These changes persisted for many years despite disease quiescence., (© 2022. The Author(s).)

Purpose: To evaluate associations between functional and structural measurements in patients with non-acute VKHD., Methods: In this cross-sectional study, 16 non-acute VKHD patients (32 eyes; 14 female) were evaluated with multifocal electroretinogram (mfERG), standardized automated perimetry (SAP) and optical coherence tomography (OCT)examinations. All included patients had a minimum 12 months of follow-up from acute onset and were participants of an ongoing prospective study since acute phase with systematic clinical imaging evaluations and electroretinogram examinations within a predefined treatment. Age- and gender-matched controls were included. Main outcomes were functional and structural abnormalities and their correlation; secondary outcome was correlation of these findings with clinical characteristics, including fundus abnormalities., Results: SAP and mfERG parameters were significantly worse in patients than in controls. Fourteen eyes (43.7%) had disrupted ellipsoid zone (EZ); visual acuity (VA) was similar between eyes with intact or disrupted EZ. Eyes with intact and disrupted EZ differed significantly concerning N1 and P1 amplitudes and N1 peak time values on mfERG and mean sensitivity (MS), central sensitivity (CS), foveal threshold, visual field index, mean deviation (MD) and pattern standard deviation values on SAP. The area under the curve on receiver operating curves for P1 amplitude was 0.81 (cut-off value = 34.7 nV/deg 2 ) and for MD value was 0.84 (cut-off value = -5.2 dB). Central retinal thickness (CRT) significantly correlated with N1 and P1 amplitudes and P1 peak time values on mfERG (r = 0.354, r = 0.442 and r = -0.405, respectively) and MD, MS, CS and fovea threshold (log values) on SAP (r = 0.372, r = 0.406, r = 0.431 and r = 0.414, respectively). Statistically significant associations were found with the presence of peripapillary atrophy and recurrent anterior uveitis with a worse MD value (p = 0.004 and p < 0.001, respectively)., Conclusion: In non-acute VKHD, disrupted EZ and reduced CRT were correlated with impaired mfERG and SAP parameters, even in patients with good VA., (© 2020 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose : To assess the effectiveness of intravitreal (IV) bevacizumab and the need for systemic immunosuppressive therapy (IMT) in choroidal neovascularization (CNV) in Vogt-Koyanagi-Harada disease (VKHD). Methods : CNV treatment consisted of three monthly IV bevacizumab injections as a loading dose; if intra/subretinal fluid (IRF) persisted, further injections were proceeded besides increment in systemic IMT. Outcome analyses at 3, 6, and 12 months were visual acuity, central foveal thickness, macular volume, IRF, and addition of IMT. Results : Seven eyes of six patients were included. Five patients (five eyes) completed a 12-month follow-up and received 12 IV bevacizumab injections. At the 12-month follow-up, visual acuity improved in four out of five eyes ( p = .0568); all eyes had decreased macular volume ( p = .0431) but they still had persistent IRF; and all cases needed IMT introduction/increment. Conclusion : Intravitreal bevacizumab in association with systemic IMT was effective for CNV in VKHD. Active CNV may indicate disease of inadequate clinical control.

Aims : To evaluate associations between vision-related (VR-) and health-related (HR-) QoL metrics and inflammation and treatment in non-acute VKHD patients. Methods : Cross-sectional study in a tertiary center in Sao Paulo, Brazil with 22 patients with non-acute VKHD followed prospectively for ≥12 months since acute disease onset, with systematic evaluation and predefined treatment protocols. VR- and HR-QoL aspects were assessed by VFQ-25 and SF-36 questionnaires, respectively. Associations between the questionnaire's subscale item scores with inflammation and systemic medical therapies were assessed. Results : After generalized linear model analysis, worse VA, severe fundus changes, fluctuation of VA and fluctuation of anterior chamber cells impacted negatively on VR-QoL items. Higher cumulative total dose of corticosteroids and use of immunosuppressive therapy impacted negatively on both questionnaires. Conclusion : Worse VA, clinical inflammation and systemic treatment have a significant impact on VR- and HR-QoL questionnaires. Subclinical choroidal inflammation did not seem to impact QoL.

Purpose : To assess health-related (HR-) and vision-related (VR-) quality of life (QoL) in patients with long-standing Vogt-Koyanagi-Harada disease (VKHD). Methods : Cross-sectional study of 49 patients with disease duration ≥12 months followed at Uveitis Service, Universidade de São Paulo, BR, for at least 12 months. HR- and VR-QoL were evaluated using SF-36 and NEI VFQ-25 questionnaires, respectively. Demographic, clinical and visual function data were compared with questionnaire scores. Results : After generalized linear models, lower mensal household income was associated with lower scores in both questionnaires while unemployment was associated with SF-36 questionnaire only. Treatment with peri-/intraocular medications and ocular surgery were associated with higher scores on SF-36 questionnaire. Worse visual acuity (VA), ocular complications and no ocular surgery were related to lower scores on NEI VFQ-25 questionnaire. Conclusions : On HR- and VR-QoL questionnaires difficulties perceived by patients with long-standing VKHD were mainly associated with socio-economic aspects, VA, local treatment and ocular complications.

Objective: To evaluate the role of intraocular fluid analysis as a diagnostic aid for uveitis., Methods: Twenty-eight samples (27 patients including 3 HIV-infected patients) with active (n=24) or non-active (n=4) uveitis were submitted to aqueous (AH; n=12) or vitreous humor (VH) analysis (n=16). All samples were analyzed by quantitative PCR for herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Toxoplasma gondii., Results: The positivity of the PCR in AH was 41.7% (5/12), with 50% (2/4) in immunocompetent and 67% (2/3) in HIV+ patients. The positivity of the PCR in VH was 31.2% (5/16), with 13% (1/8) in immunocompetent and 50% (4/8) in immunosuppressed HIV negative patients. The analysis was a determinant in the diagnostic definition in 58% of HA and 50% of VH., Conclusion: Even in posterior uveitis, initial AH analysis may be helpful. A careful formulation of possible clinical diagnosis seems to increase the chance of intraocular sample analysis being meaningful.

Purpose: To prospectively evaluate the dynamic changes of the full-field electroretinogram (ff-ERG) and its association with inflammatory signs in patients with Vogt-Koyanagi-Harada disease (VKHD) followed up after acute onset., Methods: Twelve acute VKHD patients, who were followed up for at least 24 months, were enrolled at a tertiary center from June 2011 to January 2017. Treatment consisted of intravenous methylprednisolone followed by 1 mg/kg/day of oral prednisone with a slow tapering associated with late non-steroidal immunosuppressive therapy in previously defined cases. Inflammation was systematically evaluated with clinical and posterior segment imaging (PSI) exams (fluorescein angiography, FA, indocyanine green angiography, ICGA, enhanced depth imaging optical coherence tomography, EDI-OCT). A ff-ERG was performed upon enrollment as well as at predefined intervals. Scotopic ff-ERG parameters changes between the 12th and 24th months defined the ERG-stable or ERG-worsening groups. "Flare" was defined as an appearance or worsening of inflammatory signs (after the initial 6 months following disease onset) under the predefined treatment protocol., Results: ff-ERG parameters initially improved in all eyes; in the evaluation between the 12th and 24th months, ff-ERG results were stable in 17 eyes (71 %) and worsened in 7 eyes (29 %). Subnormal ff-ERG results were observed in 15 eyes (62 %) at the 24th month. On the other hand, the flare was observed in 8 eyes (33 %) as cells in the anterior chamber and in 24 eyes (100 %) as any PSI inflammatory sign. The ERG-worsening group presented thicker subfoveal choroid at the first month (p = 0.001) and fluctuations in choroidal thickness more often during follow-up when compared to the ERG-stable group (p = 0.02)., Conclusions: Scotopic ff-ERG parameters worsened between the 12th and 24th months in a quarter of the patients. Subclinical inflammation detected as an increase in CT seems to be related to worsening in visual function measured with ffERG.

Aims: To analyse the clinical features, systemic associations, treatment and visual outcomes of uveitis in children from a referral centre in São Paulo, Brazil., Methods: Clinical records of patients under 16 years old who attended the Uveitis Service, Hospital das Clinicas, Faculdadede Medicina, Universidade de São PauloFMUSP, between April and September 2017, were reviewed retrospectively. Patients with incomplete medical records, previous ocular trauma, or less than six6 months of follow-up were excluded., Results: Thirty-nine children (25 female/14 male) were included. There was predominance of bilateral (89.7%), asymptomatic (56.4%) and recurrent/chronic cases (84.6%). The mean age at study inclusion was 10.7±3.4 years (range 3-16 years). Improvement or preservation of visual acuity (VA) was observed in 27 patients (84%); VA was not informed in 8 patients. Patients were referred early to tertiary centre (55% within 6 months of uveitis diagnosis). Anterior uveitis was the most common involvement (46%), followed by intermediate uveitis (26%). Juvenile idiopathic arthritis (JIA)-associated uveitis (41%) and immune-mediated intermediate uveitis (25.6%) were the principal non-infectious conditions; ocular toxoplasmosis (7.7%) and toxocariasis (5.1%) were the most common infectious conditions. Ocular complications were observed at first visit in 46% of patients and in 90% during final evaluation. Oral prednisone, immunosuppressive therapy (IMT) and/or biologic agents were used in all non-infectious conditions (32 children, 82%); IMT and/or biologic agents were used in all patients with JIA-associated uveitis and in 50% of patients with immune-mediated intermediate uveitis., Conclusion: Paediatric patients with uveitis are referred early to this centre and, although severe, adequate management with systemic IMT may preserve VA., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: To analyze the contribution of IgG anti-Toxocara antibodies in the diagnosis of ocular toxocariasis (OT) in serum samples of patients attending a public referral center for ophthalmology in Brazil and to determine the most frequent ocular signs and symptoms., Study Design: This was a retrospective descriptive study of a cohort of outpatients followed from December 1989 to May 2006., Methods: IgG anti-Toxocara antibody titers were determined by enzyme-linked immunosorbent assay. The results were correlated with the clinical and funduscopic findings., Results: Of the diagnoses for the 126 patients, 42 were considered as probable OT, 48 as negative, and 36 as inconclusive. The median IgG anti-Toxocara antibody titers of the patients with probable OT were significantly higher than those of the patients in the negative or inconclusive groups (P = 0.0001). Higher titers were observed more frequently in patients in the probable OT group (P = 0.01) than in the negative group, in which titers were absent or lower in most patients (P < 0.0001). The right eye was affected more in the OT group than in the negative group (P = 0.01), and inflammation was located mostly in the intermediate and posterior poles. The mean age of the patients diagnosed with probable OT was significantly lower (mean, 8 years) than that of the negative patients (mean, 14.5 years) (P = 0.006)., Conclusions: Higher levels of antibodies could help with the diagnosis of OT in patients with symptoms and clinical signs; however, negative results cannot exclude possible OT. Conversely, patients with negative serology or low titers make the diagnosis of OT less likely.

Background: Frosted branch angiitis is a rare, severe condition. It can be either a primary or a secondary condition and is characterized by rapid deterioration of vision and fulminant retinal vasculitis that manifests as diffuse sheathing of retinal vessels, macular edema, papillitis, vitritis and anterior uveitis. We aimed to describe a case of frosted branch angiitis and cerebral venous sinus thrombosis as an initial neuro-Behçet's disease onset. Diagnosis of Behçet's disease was based on the current 2014 International Criteria for Behçet's Disease and the International consensus recommendation criteria for neuro-Behçet's disease. In addition, a literature review using search parameters of "frosted branch angiitis", "Behçet" and "neuro-Behçet" in the PubMed database is presented., Case Presentation: A 28-year-old Brazilian pardo woman presented to our hospital with abrupt bilateral vision loss associated with recurrent aphthous oral ulcers 6 months before visual symptom onset. A fundus examination showed bilateral widespread retinal vasculitis with venous and arterial white sheathing, optic disc swelling, macular edema, and retinal hemorrhages, leading to the diagnosis of frosted branch angiitis. An extensive systemic workup for retinal vasculitis was uneventful, except for brain magnetic resonance imaging demonstrating cerebral venous sinus thrombosis and lymphocytic aseptic meningitis. A diagnosis of neuro-Behçet's disease was made, and treatment was started with methylprednisolone therapy 1 g/day for 5 consecutive days, followed by oral mycophenolate mofetil and infliximab 5 mg/kg infusion. The patient's response was rapid, with improvement of visual acuity to hand movement and counting fingers by day 7 and final visual acuity of counting fingers and 20/130., Conclusions: Frosted branch angiitis may be associated with infectious, noninfectious, or idiopathic causes. An extensive workup should be done to exclude systemic vasculitis such as Behçet's disease. Treatment with systemic steroids must be promptly initiated in association with specific treatment aimed at inflammation control and blindness risk reduction.

Purpose:: To evaluate the outcomes of phacoemulsification with intraocular lens (IOL) implantation in eyes with uveitis., Methods:: Consecutive patients with uveitis and cataracts who had phacoemulsification and acrylic IOL implantation during 2007-2012 were evaluated for visual outcomes, etiology, and complications. Inflammation was controlled for at least 3 months before surgery, and oral prednisone (0.5 mg/kg/day) was administered to patients with non-infectious uveitis., Results:: This study investigated 45 eyes in 38 patients with a mean age of 52 ± 12.5 years. The most common etiologies among non-infectious causes (n=32; 73.3%) were Vogt-Koyanagi-Harada disease (n=9), Fuchs heterochromic iridocyclitis (n=4), and sympathetic ophthalmia (n=3). Four cases were idiopathic. Among infectious cases (n=13; 28.9%), the most common causes were toxoplasmosis (n=6) and presumed ocular tuberculosis (n=4). An acrylic IOL was implanted in-the-bag in all cases. After 1-year follow-up, an improvement in visual acuity of two or more lines was observed in 38 eyes (84.4%), and 28 eyes (62.2%) achieved a postoperative visual acuity of ≥0.5. Posterior capsule opacification was observed in 10 eyes (22.2%). Persistent postoperative inflammation (of >6 months) was observed in seven eyes (15.5%) and recurrence occurred in four eyes (8.8%). IOL was explanted in one eye. Intraocular hypertension was observed in six eyes (13.3%)., Conclusions:: Phacoemulsification with IOL implantation improved vision in most patients with coexisting cataracts and uveitis. Good preoperative and postoperative control of inflammation plays an important role in achieving favorable visual outcomes. Furthermore, the final visual outcome depends on the posterior segment status.

Purpose:: To evaluate the efficacy and tolerance of mycophenolate mofetil (MMF) for the treatment of noninfectious uveitis using the methods advocated by the Standardization of Uveitis Nomenclature (SUN) Working Group and to compare this with other studies of immunosuppression in ocular inflammation., Methods:: Retrospective case series. Patients with noninfectious uveitis, followed at a tertiary Uveitis Service in São Paulo, Brazil, from 2007 to 2014 and receiving oral MMF for a minimum of 6 months, were retrospectively reviewed. After reaching an optimal dose of MMF, patients were evaluated after 6 (T6), 12 (T12), and 24 months (T24). The optimal dose varied for each patient (medium 2.2 g/day, range 1.0-3.0 g/day). The main outcome measures were: 1) success on achieving complete control of inflammation in both eyes and/or oral prednisone dosage reduction to ≤10 mg per day, and 2) the length of time required to reduce oral prednisone to ≤10 mg/day, partial control of ocular inflammation, and side effects., Results:: In a cohort of 16 patients with refractory noninfectious uveitis, 67% reached the ideal prednisone dose after 1 year of MMF treatment and 83% after 2 years of MMF treatment. Complete or partial inflammation control was achieved in 43.7% at T12. Two patients (14%) had disease remission after 4.7 years of MMF treatment. Adverse effects were gastrointestinal disturbances, infection, insomnia, and liver function abnormalities at a rate of 0.03 patient-year each., Conclusions:: This small retrospective case series is consistent with the literature concerning the high efficacy and moderate tolerability of MMF in noninfectious uveitis. Observation of patients should be continued for at least 1 year to clearly determine MMF efficacy.

Vogt-Koyanagi-Harada disease (VKHD) is a rare granulomatous inflammatory disease that affects pigmented structures, such as eye, inner ear, meninges, skin and hair. This disease is mainly a Th1 lymphocyte mediated aggression to melanocytes after a viral trigger in the presence of HLA-DRB1*0405 allele. The absence of ocular trauma or previous intraocular surgery sets VKHD appart from sympathetic ophthalmia, its main differential diagnosis. The disease has an acute onset of bilateral blurred vision with hyperemia preceded by flu-like symptoms. The acute uveitic stage is characterized by a diffuse choroiditis with serous retinal detachment and optic disc hyperemia and edema. Fluorescein angiography in this phase demonstrates multiple early hyperfluorescent points. After the acute uveitic stage, ocular and integumentary system pigmentary changes may appear. Ocular findings may be accompanied by lymphocytic meningitis, hearing impairment and/or tinnitus in a variable proportion of patients. Prompt diagnosis followed by early, aggressive and long-term treatment with high-dose corticosteroids is most often ensued by good visual outcomes. However, some patients may experience chronic uveal inflammation with functional eye deterioration. The current review discusses the general features of VKHD, including epidemiology, classification into categories, differential diagnosis and current therapeutic approaches.

Purpose: To analyse the rate of clinical recurrences in Brazilian patients with Vogt-Koyanagi-Harada (VKH) disease after early high-dose corticosteroid treatment., Methods: Retrospective study including patients treated with early high-dose corticosteroids (prednisone, 1-1.5 mg/kg/day, or 3-day 1 g methylprednisolone pulsetherapy) within 1 month from disease onset followed by slow taper (at least 6 months). Patients with a minimum 12-month follow-up were subdivided based on the presence of disease recurrence or persistence after 6 months from initial presentation into: acute-resolved (AR, no recurrences), chronic-recurrent (CR), and chronic-recurrent with subretinal fibrosis (SRF). Recurrences were defined as the presence of clinical and/or fluorescein angiography findings., Results: Twenty-nine patients (58 eyes) with a median follow-up of 65 months were included. Six (21 %), 11 (38 %) and 12 (41 %) patients were allocated to AR, CR, and SRF groups respectively. Though having received treatment within 1 month of onset, median time to initial treatment differed among groups (11, 15, and 25 days, in AR, CR, and SRF groups respectively). Intensity of immunosuppression, cataract development, and longer time to achieve logMAR visual acuity ≤0.8 differed significantly among the groups, being more severe in SRF group. HLA-DRB1*0405 allele followed the same trend, though not reaching significance (0.5 in AR group, 0.6 in CR, and 0.8 in SRF)., Conclusion: VKH disease in Brazilian patients evolved to chronic-recurrent disease in 79 % of cases; 38 % developed subretinal fibrosis, in spite of similar initial treatment regimens. Time to initiate treatment influenced outcomes.

Vogt-Koyanagi-Harada (VKH) disease is a systemic autoimmune disorder that affects pigmented tissues of the body, with its most dire manifestations affecting the eyes. This review focuses on the diagnostic criteria of VKH disease, including some information on history, epidemiology, appropriate clinical and classification criteria, etiopathogenesis, treatment and outcomes. Expert review of most relevant literature from the disease's first description to 2013 and correlation with the experience in the care of VKH disease patients at a tertiary Uveitis Service in Brazil gathered over the past 40 years. The clinical manifestations and ancillary assessment of VKH disease have been summarized in the Revised Diagnostic Criteria proposed in 2001 in a manner that allows systematic diagnosis of both acute and chronic patients. It includes the early acute uveitic manifestations (bilateral diffuse choroiditis with bullous serous retinal detachment and optic disk hyperemia), the late ocular manifestations (diffuse fundus depigmentation, nummular depigmented scars, retinal pigment epithelium clumping and/or migration, recurrent or chronic anterior uveitis), besides the extraocular manifestations (neurological/auditory and integumentary). There are two exclusion criteria, i.e. absence of previous ocular penetrating trauma or surgery and any other ocular disease that could be confounded with VKH disease. HLA-DRB1*0405 plays an important role in pathogenesis, rendering carriers more susceptible to disease. The primary ocular pathological feature is a diffuse thickening of the uveal tract in the acute phase. Later on, there may be a compromise of choriocapillaris, retinal pigment epithelium and outer retina, mostly due to an "upstream" effect, with clinical correlates as fundus derangements. Functional tests (electroretinogram and visual field testing) as well as imaging modalities (retinography, fluorescein/indocyanine green angiography, optical coherence tomography and ultrasound) play an important role in diagnosis, severity grading as well as disease monitorization. Though high-dose systemic corticosteroids remain gold-standard therapy, refractory cases may need other agents (cyclosporine A, anti-metabolites and biological agents). In spite of good visual outcomes in the majority of patients, knowledge about disease progression even after the acute phase and its impact on visual function warrant further investigation., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Detection of choroidal inflammation in Vogt-Koyanagi-Harada (VKH) disease is still a challenge. Progression to sunset glow fundus has been observed despite apparent good clinical control of inflammation. Indocyanine green angiography (ICGA) permits choroid inflammation detection, though it is invasive, time consuming, and costly. The purpose of the present study is to report a sign indicative of probable inflammation on enhanced depth imaging spectral-domain optical coherence tomography (EDI-OCT): a localized increase in choroidal thickness with bulging of the outer retina ('choroidal bulging') in patients with VKH disease in the non-acute uveitic stage., Findings: This is a retrospective observational study. The choroidal bulging was a particular finding observed in four eyes of three patients with VKH disease in the non-acute uveitic stage (median disease duration 55.3 ± 40.3 months, range 10 to 108). This study is part of an ongoing longitudinal study in patients with VKH disease carried out in the Uveitis Service, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil. In all eyes, the choroidal bulging was identified in the presence of anterior chamber cells and/or on fundus angiographic (fluorescein and indocyanine green) findings, indicative of disease activity. Changes in the thickness of the choroidal bulging accompanied the variation in the clinical and angiographic signs of inflammation., Conclusion: The choroidal bulging is a particular finding detected on EDI-OCT that may indicate ongoing inflammation in the posterior segment of the eye. This EDI-OCT feature may assist in the treatment-monitoring of patients with Vogt-Koyanagi-Harada disease in the non-acute uveitic stage.

Aim: To evaluate the choroidal thickness (CT) in patients with long-standing Vogt-Koyanagi-Harada (VKH) disease using enhanced depth imaging optical coherence tomography (EDI-OCT)., Methods: A prospective case-control study developed at a tertiary centre at São Paulo, Brazil. EDI-OCT images were obtained in 16 patients (30 eyes) with VKH disease who had had the disease for more than 6 months since disease onset, and in 17 normal individuals controlled by age (32 eyes). Comprehensive ophthalmic examination and EDI-OCT evaluation were performed. CT was measured at the fovea and at 1000 µm intervals from the foveal centre in both temporal and nasal directions. CT was correlated with disease duration, clinical disease activity and fundus-based disease severity., Results: Mean subfoveal CT was 333 µm (±85.8) in controls and 250.7 µm (±93.3) in VKH patients (p=0.002). The choroid was significantly thinner in patients when compared to controls in all but one nasal point. In patients, the CT measurements at the foveal centre presented a negative correlation with disease duration (p<0.001). No significant difference in CT measurements was observed between eyes with and without clinical inflammation (p=0.42). There was a trend towards more severe fundus changes being associated with a thinner choroid (p=0.28)., Conclusions: Patients with VKH and long-standing disease had thinner choroids when compared to controls. Progressive choroidal thinning related to disease duration was observed at the macula of these patients. Whether this finding is part of the natural history of the disease or the result of a clinically undetected choroidal inflammation remains to be determined.

Background: To investigate indocyanine green angiography (ICGA) findings in patients with long-standing Vogt-Koyanagi-Harada (VKH) disease and their correlation with disease activity on clinical examination as well as with systemic corticosteroid therapy., Methods: Twenty-eight patients (51 eyes) with long-standing (≥6 months from disease onset) VKH disease whose treatment was tapered based only in clinical features were prospectively included at a single center in Brazil. All patients underwent standardized clinical evaluation, which included fundus photography, fluorescein angiography and ICGA. Clinical disease activity was determined based in the Standardization in Uveitis Nomenclature Working Group. Fisher exact test and logistic regression models were used for statistical analysis., Results: Disease-related choroidal inflammation on ICGA was observed in 72.5% (31 of 51 eyes). Angiographic findings suggestive of (choroidal and/or retinal) disease activity were not observed on FA. Clinically active disease based on clinical evaluation was observed in 41.2% (21 of 51 eyes). In these 21 eyes, disease-related choroidal inflammation on ICGA was observed in 76.2% (16 of 21 eyes); in the remaining eyes (without clinical active disease) disease-related choroidal inflammation on ICGA was observed in 70.0% (21 of 30 eyes). In respect to systemic corticosteroid therapy, 10 patients (18 of 51 eyes) were under treatment with prednisone. In these 10 (18 of 51 eyes) patients, disease-related choroidal inflammation on ICGA was observed in 83.3% (15 of 18 eyes); in the remaining patients (33 of 51 eyes) disease-related choroidal inflammation on ICGA was observed in 66.7% (22 of 33 eyes)., Conclusion: ICGA findings suggestive of disease-related choroidal inflammation were observed in a considerable proportion of patients with long-standing VKH disease, independent of the inflammatory status of the disease on clinical examination or current use of systemic corticosteroid. Therefore, the current study reinforces the crucial role of ICGA to assist the management and treatment of patients with long-standing VKH disease.

Purpose: To assess the efficacy and side effects of immunosuppressive therapy in patients with Behçet's disease uveitis., Methods: A nonrandomized retrospective case-series study analyzed data from 22 patients with Behçet's disease uveitis, from a single Uveitis Service, São Paulo, Brazil (period 1978-2007), under systemic chlorambucil and/or cyclosporine A, for at least 6 months with a minimum one-year follow-up. Drug efficacy was measured by reduction in relapse rate and reduction of prednisone dose., Results: Patients (10M/12F) mean age was 29 (range 10-43) years-old at the onset of uveitis. The median duration of followup was 11 (range 1-29) years-old. Chlorambucil (2-6 mg/day) was used in 13 patients and cyclosporine A (3-5 mg/kg/day) in 9 patients at initiation. Drugs were switched because of no effectiveness or side-effects. Chlorambucil was effective in 78.5% (11/14) and induced disease remission in 43% (6/14) of patients, whereas cyclosporine A was effective in 57% (8/14) of patients. Chlorambucil and cyclosporine A were discontinued due to side effects in 21% (leucopenia) and in 57% of patients (nephrotoxicity, 36% and gastrointestinal complications, 21%), respectively. No case of late malignancy was observed. 36% (16/44) of eyes had final visual acuity < or =0.1, among which 69% (11/16) had already this visual acuity at the first visit., Conclusion: This study reiterates previous data that chlorambucil can induce long-term remission of Behçet's disease uveitis, whereas cyclosporine is effective but side effects limit its use. Chlorambucil therapy may still be a reasonable option in patients with intractable, sight-threatening Behçet's disease uveitis.

Although human toxocariasis ranks among the most common zoonotic infections worldwide, it remains relatively unknown to the public. The causal agents are the nematode parasites Toxocara canis and T. cati, whose definitive hosts are dogs and cats, respectively. When embryonated eggs are accidentally ingested by humans, larvae hatch in the small intestine, penetrate the intestinal wall and migrate, via the bloodstream, to the liver, lungs, muscles, eye and central nervous system. Although most human infections are asymptomatic, two well-defined clinical syndromes are classically recognised: visceral larva migrans (a systemic disease caused by larval migration through major organs) and ocular larva migrans (a disease limited to the eyes and optic nerves). Two less-severe syndromes have recently been described, one mainly in children (covert toxocariasis) and the other mainly in adults (common toxocariasis). Here, the current laboratory diagnosis, epidemiology and main clinical features of both the systemic and ocular forms of human toxocariasis are reviewed. New developments in serological diagnosis are described, the available seroprevalence data are analysed, and the results of relevant clinical studies that have been published over the last decade are explored, to provide an updated overview of this neglected but highly prevalent human infection.

Purpose: To propose an analytic framework for ocular fundus alterations in late-stage Vogt-Koyanagi-Harada (VKH) disease, to describe the characteristics of overall retinal function as measured with full-field electroretinography (ERG), and to correlate the intensity of the fundus changes with full-field ERG alterations and to stratify patients accordingly., Design: Cross-sectional case series., Methods: Forty-seven eyes of 26 patients with late-stage VKH disease (> 6 months past disease onset) followed-up at the University of São Paulo School of Medicine underwent fundus photography within 2 months of a full-field ERG examination, both according to predefined protocols. Fundus pictures were evaluated by two observers regarding diffuse fundus depigmentation, nummular lesions, pigment clumps, and subretinal fibrosis, and an overall analysis classified the fundus changes as mild, moderate, or severe. Full-field ERG results were analyzed according to fundus-based stratification and also were stratified into 3 groups solely on the basis of decreasing amplitudes (ERG based or cluster stratification). The concordance between fundus-based and full-field ERG-based stratification strategies was estimated., Results: Overall fundus grading showed substantial interobserver concordance (kappa = 0.78). Comparison of full-field ERG parameters of the three fundus-based stratified groups showed diffusely diminished amplitudes with preservation of implicit times (P < .05). Fundus-based and full-field ERG-based stratification strategies also showed substantial concordance (kappa = 0.68)., Conclusions: The analytic framework for fundus findings proposed in this study seems reproducible and useful, because the severity categories do correlate with retinal function as measured by full-field ERG. This system may allow more precise exchange of information between practitioners as well as researchers with regard to identifying patients with greater retinal compromise rapidly as well as in comparison of outcomes of different treatment regimens.

Purpose: To evalulate the applicability of the Revised Diagnostic Criteria for Vogt-Koyanagi-Harada (VKH) disease to Brazilian patients and to verify the association between different disease categories, clinical parameters, and the presence of HLA-DRB1*0405., Design: A retrospective observational case series., Methods: Medical charts of 67 patients (10 to 64 years in age; 12 men and 55 women), from the Uveitis Service, Hospital das Clínicas, University of São Paulo School of Medicine (HCFMUSP), São Paulo, Brazil were reviewed. Patients, previously diagnosed with VKH disease using criteria proposed by the American Uveitis Society, underwent retrospective classification based on the Revised Diagnostic Criteria. The degree of concordance was assessed. At presentation, 46 patients (69%) were in the early phase. In this group, the mean time from disease onset to treatment was 15 days (range, one to 30 days). Forty-eight patients (72%) were typed for HLA-DRB1*0405 by polymerase chain reaction-sequence specific primer and polymerase chain reaction-sequence-specific oligonucleotides primer. Disease categories, phase at initial presentation, and ocular complications were analyzed., Results: There was a 100% of concordance between the two criteria. Disease was classified as complete in 10 patients (15%), incomplete in 37 patients (55%), and probable in 20 patients (30%). In each group, respectively, 90%, 76%, and 45% were in the early phase at presentation (P = .017). There was no association between disease categories, the presence of HLA-DRB1*0405, and clinical parameters., Conclusion: The Revised Diagnostic Criteria proved useful for diagnosis of VKH disease in Brazilian patients. The present retrospective study did not find any association between disease category and severity parameters. To better understand the relevance of disease categories, a minimum follow-up period to categorize patients should be included in future prospective studies.

Background: Ocular toxocariasis is usually a unilateral posterior uveitis in otherwise asymptomatic children. The authors report the rare occurrence of presumed ocular toxocariasis presenting as a juxtapapillary lesion in a 52-year-old woman with systemic manifestations of visceral larva migrans., Case Report: A 52-year-old woman presented with blurred vision in her right eye for 2 months. She shared her bedroom with two puppies. Best-corrected visual acuity was 20/20 in both eyes; slit-lamp examination was unremarkable. Funduscopy revealed a whitish, elevated, juxtapapillary retinochoroidal lesion of approximately one disk diameter size with macular star formation. She also developed severe respiratory distress and diarrhea. An intense eosinophilia was detected. Investigation included a liver biopsy positive for Toxocara antigens upon staining with chromogen 3,3'-diaminobenzidin and anti-Toxocara immunoglobulin G >10,240 (enzyme-linked immunosorbent assay). Treatment with albendazole and corticosteroids was implemented. Third generation optical coherence tomography (Stratus Tomographer, Model 3,000, Carl Zeiss Ophthalmic Systems, Inc., Dublin, CA) (OCT) of the macular area was unremarkable, except for a slight increase in retinal thickness as it approached the inflammatory lesion. Two months after treatment, there was a hypopigmented scar with localized condensed vitreous opacities. The OCT demonstrated traction along the vitreoretinal interface as the inflammation waned. A conservative approach was maintained as visual acuity remained stable., Conclusion: OCT imaging may offer a practical means of locating and staging posterior pole lesions due to ocular toxocariasis.

We report the case of a 40-year-old woman with diffuse uveitis, sensorineural hearing loss and cerebrospinal fluid pleocytosis as features of Vogt-Koyanagi-Harada syndrome who developed symmetric polyarthritis and stiffness of small and large joints, in addition to rheumatoid arthritis. Although their target tissues are distinct, both diseases have a possible autoimmune origin strongly associated with HLA-DRB4.

Objectives: Although human T-cell lymphotropic virus type 1 (HTLV-1)-associated uveitis has been well recognized in Japan, related studies in Brazil are scarce. We performed a serologic survey for HTLV-1 infection among patients with uveitis and investigated the ocular findings in HTLV-1-asymptomatic carriers., Methods: One hundred ninety serum samples from patients with uveitis of determined (n = 137) and undetermined origins (n = 53) being examined at the Uveitis Service, University of São Paulo, São Paulo, Brazil, underwent testing using HTLV enzyme-linked immunosorbent assay and discriminatory Western blots. One hundred five asymptomatic blood donors and/or their relatives who were seropositive for HTLV-1 (carrier group) and 105 age- and sex-paired blood donors who were seronegative for HTLV-1 (control group) underwent ocular evaluation. For the statistical analysis, chi2 test was used., Results: Only 1 patient with uveitis was seropositive for HTLV- 1, and she belonged to the group with uveitis of undetermined origin. Results of tear films were evaluated in 52 carriers. The prevalence of a decreased tear break-up time was significantly higher in the carrier compared with the control group (P = .02). Two carriers had keratoconjunctivitis sicca. Three of the 105 carriers exhibited mild uveitis (cells in the vitreous, retinal and choroidal infiltrates, retinal vasculitis, and bilateral pars planitis). Retinal pigmentary changes were found in both groups (no statistical difference)., Conclusions: Early tear abnormalities may be present in asymptomatic carriers, and mild uveitis may be found among them. The relatively low seroprevalence of HTLV-1 in the Brazilian population made it difficult to establish the real importance of HTLV-1-associated uveitis among our patients with uveitis.

Vogt-Koyanagi-Harada (VKH) disease is a rare disorder affecting pigmented structures especially the eye and is the main cause of autoimmune non-infectious uveitis in the Brazilian population. The autoimmune target is believed to be the melanocyte. A strong association of VKH disease with HLA-DR4 in the Japanese population is well known. The same association, albeit with lower relative risks has been found in other populations. A secondary association to HLA-DR1 involving a sequence linked with susceptibility to Rheumatoid Arthritis has also been described. VKH disease is more common in non-Caucasian populations. Brazilian patients of varying ethnic origins have been typed for HLA class II antigens. Several of the features found in other population samples are present. Over half of the patients typed HLA-DR4 (20/37) and typing with sequence-specific oligonucleotides disclosed predominance of the DRB1*0405 allele with a relative risk of 11.76 over the general population. In addition, HLA-DR1 and DQ4 were also present, in patients both positive and negative for HLA-DR4. These results suggest that, as in other autoimmune diseases, multiple overlapping susceptibility factors encoded by the MHC complex contribute to the overall susceptibility for the disease, the major factor however, being the presence of the DRB1*0405 allele.