Edilberto Olivalves

HLA-DRB1∗0405 is the Predominant Allele in Brazilian Patients With Vogt-Koyanagi-Harada Disease

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.

Enhanced depth imaging optical coherence tomography in long-standing Vogt–Koyanagi–Harada disease

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.

Revised Diagnostic Criteria for Vogt-Koyanagi-Harada Disease: Considerations on the Different Disease Categories

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.

Chlorambucil and cyclosporine A in Brazilian patients with Behçet's disease uveitis: a retrospective study

PURPOSE To assess the efficacy and side effects of immunosuppressive therapy in patients with Behçets disease uveitis. METHODS A nonrandomized retrospective case-series study analyzed data from 22 patients with Behçets 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 Behçets 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 Behçets disease uveitis.

Fundus-Based and Electroretinographic Strategies for Stratification of Late-Stage Vogt-Koyanagi-Harada Disease Patients

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.

Indocyanine green angiography findings in patients with long-standing Vogt-Koyanagi- Harada disease: a cross-sectional study

BackgroundTo 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.MethodsTwenty-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.ResultsDisease-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).ConclusionICGA 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.

Severe bilateral necrotising retinitis caused by Toxoplasma gondii in a patient with systemic lupus erythematosus and diabetes mellitus

Ocular toxoplasmosis may be remarkably atypical in situations of evident immunosuppression such as acquired immunodeficiency syndrome, malignancy, and use of chronic immunosuppressive drug therapy.1 Aggressive forms in immunocompetent hosts are very rare.2,3 We present a case of severe, bilateral necrotising retinitis by Toxoplasma gondii initially misdiagnosed as an acute retinal necrosis (ARN) syndrome, in a patient with systemic lupus erythematosus (SLE) and diabetes mellitus type 2, who was taking medium dose prednisone. A 47 year old woman reported a 3 month history of rapid visual loss in the right eye followed by a decrease in her left eye vision 2 months later. Twenty days before the onset of ocular symptoms the patient had a seizure. Her medical history showed a SLE,4 with an active lupus central nervous system disease controlled with prednisone (0.5 mg/kg/day), and type 2 diabetes mellitus. At her first visit to our service, visual acuity was hand movements in both eyes. Slit lamp examination showed 3+ aqueous cells and flare, and 2+ anterior vitreous cells in both eyes. The fundus showed a 2+ vitreous haze and almost 360° creamy white necrotising retinitis extending from the ora serrata to the posterior pole, including the macula in both eyes (Fig 1A and B). Thumbprint patches at the border between necrotic and scanty normal retina could be observed, and also diffuse vascular attenuation. Figure 1 (A) Fundus appearance of …

Inflamação idiopática da órbita com extensão extra-orbital: relato de caso

The authors report a case of a patient with idiopathic orbital inflammation with extension beyond the orbit. Biopsy was performed to confirm the diagnosis of idiopathic orbital inflammation and computed tomography demonstrated the extraorbital extension. Treatment with methotrexate and radiotherapy was used.

Outcomes of phacoemulsification in patients with uveitis at a tertiary center in São Paulo, Brazil: a review of cases from 2007 to 2012

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.

Mycophenolate mofetil as an immunomodulator in refractory noninfectious uveitis

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.