Repeated pulse corticosteroid therapy in Vogt-Koyanagi-Harada disease. A case report

Vogt-Koyanagi-Harada disease is an autoimmune bilateral uveitis that occurs in people with genetic sensitivity. Diagnosis was based on the association of ocular inflammatory manifestations such as diffuse choroiditis, with or without anterior uveitis, and extraocular manifestations such as meningismus, tegumentary or auditory findings. Intravenous pulses of corticosteroid followed by oral corticosteroid is the mainstay therapy. We present the case of a woman who showed a first improvement of symptoms with three consecutive daily pulses of corticosteroid, but none during the following oral therapy. A second phase of intravenous pulses of corticosteroid, a Month after the first one, induced great improvement in symptoms and retinal findings, whereas oral therapy seemed not to be effective. This case provides the opportunity for a discussion on the advantages of multiple pulses of corticosteroid at the acute phase of this disease, because of its vascular effects associated with anti-inflammatory effects.     

Systemic corticosteroid treatment in Vogt-Koyanagi-Harada disease

Twenty patients with Vogt-Koyanagi-Harada disease who had been given systemic corticosteroids were retrospectively analyzed. Sixteen patients were successfully treated with systemic corticosteroids without recurrence of uveitis. Since the advent of corticosteroid treatment, there have been fewer ocular complications as well as extraocular signs and symptoms in most cases. Recurrence of the inflammation, however, occurred in four cases. Drip infusion of 200 mg prednisolone daily, widely employed for the treatment, did not always have good results. It is suggested that the dosage of corticosteroid should be adjusted according to the severity of uveomeningitis. Oral administration of corticosteroid (less than 100 mg prednisolone daily) may be enough for suppression of the inflammation in the Harada type, while a drip infusion of the massive dosage (more than 200 mg prednisolone daily) with gradual tapering off is possibly requisite in the Vogt-Koyanagi type.     

Correlation between peripapillary atrophy and corticosteroid therapy in patients with Vogt-Koyanagi-Harada disease

AIMS: To determine the correlation between systemic corticosteroid therapy and the occurrence and size of peripapillary atrophy (PPA) in patients with Vogt-Koyanagi-Harada (VKH) disease. METHODS: All patients with VKH disease were retrospectively reviewed for their corticosteroid regimen. The extent of the PPA, if present, was measured using digitized imaging software, by two masked observers. Eyes with myopia greater than 6 dioptres or glaucoma were excluded. The patients were classified into three groups: early high (EH), late high (LH), and low dose (LD), according to the dose and timing of corticosteroids received during the acute phase of the disease. RESULTS: There were 40 eyes in the EH group, 25 eyes in the LH group, and 23 eyes in the LD group. Multivariate analysis showed that corticosteroid therapy was the main determinant of PPA occurrence. All the eyes in the LD group had PPA and eyes in the LH groups were 4.02 times (95% confidence interval 1.24-13.07) more likely to develop PPA than those in the EH group. The LD group also had larger PPA to disc ratios than the EH group. (Mean of 2.83 vs0.19, P<0.001). CONCLUSION: The development and extent of PPA in patients with VKH disease appear to be dependent on the dose and timing of systemic corticosteroids.     

Vogt-小柳-原田综合征的大量激素疗法

目的探讨Vogt-小柳-原田综合征的大量激素治疗的临床经过及荧光素眼底血管造影(fundus fluorescein angiography，FFA)、吲哚青绿(fundus indocyanine green agiography，ICGA)眼底血管造影在不同时期的改变情况。方法分析1992年1月至1995年12月间日本关西医科大学眼科教研室应用大量激素治疗Vogt-小柳-原田综合征新鲜病例31例62眼。运用大剂量强的松龙，方法为首剂每日100—200mg行静脉滴注，根据眼底改变及FFA、ICGA所见改变情况而行激素递减，激素最低用药期限为6个月。结果激素治疗开始后，FFA造影平均10d后开始改善，渗出性视网膜脱离及后极部视网膜水肿的消退时间平均为36d，ICGA造影平均78d开始改善。在激素递减过程中，由于眼底所见恶化而增加激素用量的病例有6例，而激素用药停止后未见复发病例。结论大量激素疗法治疗Vogt-小柳-原田综合征是行之有效的，治疗过程中如果对激素逐渐减量、间歇给药的话可以预防Vogt-小柳-原田综合征的复发，同时激素的减量应按照FFA和ICGA造影所见的共同改善情况而减量。     

Photodynamic therapy for subfoveal choroidal neovascularisation in Vogt-Koyanagi-Harada disease

AIM: To assess the effects of photodynamic therapy (PDT) with verteporfin in the treatment of subfoveal choroidal neovascularisation (CNV) secondary to Vogt-Koyanagi-Harada disease (VKH). METHODS: Six eyes of six patients with VKH who developed subfoveal CNV underwent standard PDT. Repeated treatments were performed at 3 month intervals for persistent leakage. Charts and angiographic data were analysed retrospectively. RESULTS: Age of patients ranged between 17 years and 27 years. Five CNV lesions were recent and classic (greatest lesion diameter was 1100-3100 microm). One CNV was chronic and partially scarred. Mean visual acuity (VA) at presentation was 20/200. Five patients had more than 1 year of follow up. In five eyes there was active inflammation and CNV. Of these eyes, the first three required one PDT each. The final CNV scar was smaller/stable with improvement of VA in two eyes. The third developed a larger CNV scar with loss of two lines of VA. Submacular fibrosis developed in all three. In the fourth eye, mild CNV leakage persisted after one PDT but hazy media precluded a second PDT. At 18 months the CNV scar and VA were stable. The fifth case, with mild inflammation, required three PDT. The CNV leakage became minimal, the lesion became smaller, and VA improved significantly. The sixth eye with CNV had no inflammation and needed two PDT sessions to halt the CNV leakage. The final lesion was smaller and vision was stable. There were no PDT related complications in our series. CONCLUSION: Photodynamic therapy with verteporfin appears to be a safe and viable treatment option for subfoveal CNV secondary to VKH. It offers a chance for stabilisation or even improvement of vision. Further study is warranted.     

Vogt-Koyanagi-Harada disease

Vogt-Koyanagi-Harada (VKH) disease affects primarily persons who are Asian, Latino, Native American, or Asian Indian. Women appear to be affected more commonly than men, and VKH disease may occur at all ages, including childhood. Experimental data continue to support an autoimmune etiology for VKH disease, directed most probably against an antigenic component of the melanocyte, possibly tyrosinase or a tyrosinase-related protein. The clinical diagnosis of VKH disease continues to be based on physical findings. Newer imaging modalities such as magnetic resonance imaging, indocyanine green angiography, and digital image analysis have not added appreciably to our understanding of the condition. First-line therapy consists of high-dose corticosteroids, with use of corticosteroid-sparing agents for resistant or recalcitrant disease. Complications are the main cause of reversible and irreversible vision loss, with subretinal fibrosis and choroidal neovascular membranes having particularly poor prognoses.     

不同种类糖皮质激素治疗Vogt-小柳-原田综合征的疗效分析

目的：探讨Vogt-小柳-原田综合征(Vogt-Koyanagi-Harada syndrome,VKHS)的诊断及不同糖皮质激素治疗VKHS的临床疗效。

方法：回顾性分析本院2010-01/2014-02收治VKHS 45例90眼。按糖皮质激素种类不同分为两组：观察组25例50眼：静滴注射用甲基强的松龙(1.0g)3d后,减量为0.5g治疗2d,然后改为晨起顿服强的松片(60mg); 对照组20例40眼：静滴地塞米松注射液(12mg)5d,然后改为晨起顿服强的松片(60mg)。两组均随炎性反应减轻逐渐减量,每次减5mg,当药物减至15～20mg时,维持治疗>6mo,再逐渐减量直至停药,总疗程≥9mo。观察分析治疗前后患者视力、光学相干断层扫描(optical coherence tomography,OCT)及荧光素眼底血管造影(fundus fluorescein angiography,FFA)变化情况。

结果：两组治疗前视力差异无统计学意义,治疗5d后视力均有提高,且观察组视力(0.44±0.19)优于对照组(0.55±0.29),差异有统计学意义(P<0.05); 治疗15d后,两组视力均进一步提高,观察组视力(0.32±0.17)好于对照组(0.39±0.22),差异无统计学意义; 治疗30d后,两组视力基本恢复正常。治疗前有84眼(93%)OCT检查显示视网膜黄斑中心凹存在神经上皮层脱离或视网膜浆液性脱离,脱离高度为观察组1009.67±319.40μm,对照组1098.13±283.45μm。治疗5d后,两组视网膜下积液明显吸收,观察组脱离高度(307.79±71.35μm)低于对照组(434.13±88.67μm),两组间差异有显著统计学意义(P<0. 01); 治疗15d后,两组黄斑中心凹视网膜下液基本吸收,观察组为290.61±52.55μm,对照组为296.55±61.57μm,差异无统计学意义; 治疗30d后,两组黄斑中心凹形态基本恢复正常。治疗30d后,大部分患眼荧光素眼底血管造影基本正常,仅8眼有轻度视盘渗漏。

结论：早期大剂量甲基强的松龙冲击治疗VKHS可快速提高患者视力,促进视网膜下液吸收,临床疗效优于地塞米松,而且不良反应少,值得推广。     

Vogt-Koyanagi-Harada disease

Vogt-Koyanagi-Harada disease is a chronic, granulomatous systemic autoimmune disease with manifestations in the ocular, central nervous, auditory, and integumentary systems. The target of attack seems to be antigens associated with melanocytes. Patients are usually of Asian, Middle Eastern, Asian Indian, Native American, or Hispanic ethnicity, and complain of neurologic symptoms quickly followed by decreased vision caused by a choroiditis, frequently with exudative retinal detachments. Corticosteroids are the mainstay of therapy, but other immunosuppressive therapy may be required. Complications, including cataract, glaucoma, choroidal neovascular membrane formation, and subretinal fibrosis, may limit final visual acuity.     

Vogt-Koyanagi-Harada disease

Vogt-Koyanagi-Harada disease (VKH) is a multisystem autoimmune disorder principally affecting pigmented tissues in the ocular, auditory, integumentary and central nervous systems. Patients are typically 20 to 50 years old and have no history of either surgical or accidental ocular trauma. Pigmented races are more commonly affected. Depending on revised diagnostic criteria, the disease is classified as complete, incomplete or probable based on the presence of extraocular findings (neurological, auditory and integumentary). The clinical course of VKH is divided into four phases: prodromal (mimics a viral infection), uveitic (bilateral diffuse uveitis with papillitis and exudative retinal detachment), convalescent (tissue depigmentation), and chronic recurrent (recurrent uveitis and ocular complications). The pathogenesis of VKH is thought to be related to an aberrant T cell-mediated immune response directed against self-antigens found on melanocytes. VKH has been linked to human leukocyte antigen DR4 (HLA-DR4) and HLA-Dw53, with strongest associated risk for HLA-DRB1*0405 haplotype. The diagnosis of VKH is clinical, and differential includes sympathetic ophthalmia, sarcoidosis, primary intraocular B-cell lymphoma, posterior scleritis, and uveal effusion syndrome. Treatment is typically initiated with high-dose oral corticosteroids, but other immunomondulatory agents (most oftentimes cyclosporine) may be needed for non-responsive patients or when corticosteroid side-effects are not tolerated. Visual prognosis is generally good with prompt diagnosis and aggressive immunomodulatory treatment.     

Choroidal folds in Vogt-Koyanagi-Harada disease

PURPOSE: To analyze choroidal folds in Vogt-Koyanagi-Harada (VKH) disease by fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT). DESIGN: Retrospective, consecutive case series. METHODS: Records of 95 patients diagnosed with VKH disease from October 2001 to July 2006 were reviewed. All patients underwent FA, 17 patients underwent ICGA, and 20 underwent OCT. RESULTS: Of the 95 patients, 11 (12.0%) had choroidal folds and showed 10 to 15 hypofluorescent bands radiating from the optic disk that were similar to the large retinal vessels in shape and number on FA. On ICGA, the choroidal folds showed hyperfluorescence at the late stage. OCT showed clear folds but the number of folds was larger than on FA and ICGA. CONCLUSIONS: Choroidal folds are not uncommon in VKH disease. FA, ICGA, and OCT can help to identify their pathogenesis.     

Vogt-Koyanagi-Harada disease in monozygotic twins

We encountered two cases of Harada's disease in monozygotic twins, and this is the first such report as far as could be determined. Case 1 was a 32-year-old woman who presented a typical clinical picture of Harada's disease. Seven years later, case 2 (the younger sister), also presented with the disease at 39 years of age. Case 2 had a transitional diffuse type of Harada's disease, which was possibly due to differences in her treatment. Both patients had papilledema. Since these twins both developed Harada's disease, it is suggested that hereditary factors including HLA type are very important in its development. The HLA type of both these patients was A2, A26, B51, B7, CW7, DR1, and DR4.     

Prognostic factors in Vogt-Koyanagi-Harada disease

Purpose To identify prognostic factors for final visual outcome, development of complications, and recurrent inflammation in patients with Vogt-Koyanagi-Harada (VKH) disease. Methods All patients diagnosed with acute uveitis associated with VKH disease at the King Khaled Eye Specialist Hospital and King Abdulaziz University Hospital between January 1999 and February 2004 were reviewed. Data collected included age, gender, initial and final visual acuities, clinical findings at presentation, interval between onset of disease and starting treatment, treatment received, complications, number of recurrences, extraocular manifestations, and duration of follow-up period. Results Sixty-eight patients were identified. There were 51 (75%) females and 17 (25%) males with a mean age of 25.04 ± 10.28 years (range 7–55 years). The mean follow-up period was 34.4 ± 20.1 months (range 8–62 months). The following factors were significantly associated with final visual acuity of 20/20 by univariate analysis: good initial visual acuity of better than 20/200 (p = 0.0415), absence of posterior synechiae of the iris at presentation (p = 0.0106), use of systemic corticosteroids for longer than nine months (p = 0.0479), slow tapering of systemic corticosteroids (p = 0.0024), absence of complications (p < 0.001), and absence of extraocular manifestations (p = 0.0124). Logistic regression analysis identified the use of systemic corticosteroids for longer than nine months to be associated with final visual acuity of 20/20 [odds ratio = 3.4; 95% confidence interval (CI) = 1.14–10.1]. The following factors were significantly associated with the development of complications by univariate analysis: age older than 18 years (p = 0.0161), initial visual acuity of 20/200 or worse (p = 0.0011), and presence of posterior synechiae of the iris at presentation (p = 0.0453). Factors identified after logistic regression analyses were age older than 18 years (odds ratio = 3.3; 95% CI = 1.33–8.17), and presence of posterior synechiae of the iris at presentation (odds ratio = 3.42; 9% CI = 1.38–8.47). Initial visual acuity of better than 20/200 was significantly associated with a lower risk of developing complications (odds ratio = 0.283; 95% CI = 0.129–0.629). The following factors were significantly associated with recurrent inflammation of three times or more by univariate analysis: initial visual acuity of 20/200 or worse (p = 0.0179), anterior chamber reaction of more than 2+ at presentation (p < 0.001), rapid tapering of systemic corticosteroids (p < 0.001), and development of extraocular manifestations (p = 0.0277). Conclusions Clinical findings at presentation, duration and method of tapering of systemic corticosteroids, and development of extraocular manifestations are significantly associated with final visual acuity, development of ocular complications, and recurrent inflammation. The development of ocular complications was significantly associated with a worse final visual acuity.