Full-field electroretinogram behavior in Vogt-Koyanagi-Harada disease: a 24-month longitudinal study in patients from acute onset evaluated with multimodal analysis.

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.

Vogt-Koyanagi-Harada disease: review of a rare autoimmune disease targeting antigens of melanocytes.

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.

High rate of clinical recurrence in patients with Vogt-Koyanagi-Harada disease treated with early high-dose corticosteroids.

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.

Choroidal bulging in patients with Vogt-Koyanagi-Harada disease in the non-acute uveitic stage.

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.

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

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.