Pathology of Vogt–Koyanagi–Harada disease

Typical histopathologic features of Vogt–Koyanagi–Harada disease (VKH) include granulomatous panuveitis with preservation of the choriocapillaris and exudative retinal detachment. In the chronic stage of the disease, however, histologic changes consist of nongranulomatous uveitis followed, in the chronic recurrent stage, by granulomatous uveitis and involvement of the choriocapillaris. In chronic VKH the peripheral fundus scars are not Dalén–Fuchs nodules; they are, instead, indicative of focal chorioretinal atrophy with loss of retinal pigment epithelium.     

Vogt–Koyanagi–Harada disease diagnostic criteria

Several different sets of criteria have been proposed to establish the diagnosis of Vogt–Koyanagi–Harada disease (VKH). Various investigators have used the criteria proposed by Sugiura, those proposed by by the American Uveitis Society as well as the revised diagnostic criteria proposed by the First VKH International Workshop group. These three sets of criteria share several clinical features that are considered to be essential for establishing the diagnosis of VKH, including bilateral uveitis, meningismus, and other extraocular changes. The detection of cerebrospinal fluid pleocytosis is considered to be an absolute in the criteria proposed by Sugiura but is not required for the diagnosis of VKH by the revised diagnostic criteria. We applied the latter diagnostic criteria to 28 well-documented patients with early phase VKH and to 88 patients examined during the late phase of VKH. All of these early and late phase patients fulfilled the criteria of the revised diagnosti c criteria proposed by the workshop group, indicating 100% concurrence. However, none of the above proposed criteria were prospectively validated to show the positive and negative predictive value of the proposed criteria. Such a prospective study should be undertaken to address the validity of any one or all of the above sets of VKH diagnostic criteria.     

Vogt–Koyanagi–Harada disease in Hispanic patients

Purpose To describe the clinical features of Vogt–Koyanagi–Harada disease (VKH) in Hispanic patients. Methods Retrospective review of the records of 48 Hispanic patients diagnosed with VKH. The patients were divided into two groups: patients in the early phase of VKH (n = 11) were those who presented within 1 month after the onset of symptoms; patients in the late or chronic VKH phase (n = 37) were those who presented 6 months after onset of symptoms. Demographic data, clinical features, complications and initial and final visual acuity for each patient were recorded. Results All 11 patients in early phase VKH presented with bilateral uveitis (100%). Meningismus was noted in six cases and auditory disturbances in three. Ocular findings for these 11 patients included exudative retinal detachment in ten patients (91%) and marked optic disc edema in one patient. In the late phase VKH, ocular findings included sunset glow fundus in 26 patients (70%), peripheral nummular scars in 27 (73%), and retinal pigment epithelium hyperplasia in seven (19%). Extraocular manifestations noted in this group of patients included vitiligo in four, poliosis in six, and alopecia in five; auditory disturbances were found in four patients. The visual acuity improved in 60–70% of the patients after treatment with corticosteroids alone or in combination with immunosuppressive agents. Conclusion Hispanic patients with VKH often present without extraocular changes during early phase of the disease. However, once the disease evolves into the chronic phase, integumentary system involvement may become apparent in some patients. The authors have no proprietary interest in any of the materials presented herein.     

Vogt–Koyanagi–Harada disease presenting as optic neuritis

Vogt-Koyanagi-Harada (VKH) disease is a granulomatous multisystem inflammatory disorder that classically affects the uvea, inner ear, meninges, and skin. We report three patients who presented with initial findings suggestive of bilateral optic neuritis requiring CSF analysis and brain images. None of these patients had extraocular changes. Fluorescein angiography of the retina led to the diagnosis of VKH disease in all patients. Vogt-Koyanagi-Harada disease should be included in differential diagnosis of bilateral optic neuritis, even when extraocular manifestations of the disease are absent. In such cases, fluorescein angiography will aid diagnosis.     

Trabecular meshwork depigmentation in Vogt–Koyanagi–Harada disease

Purpose

Since some patients develop depigmentation of the trabecular meshwork in the course of Vogt–Koyanagi–Harada (VKH) disease, we examined the incidence of trabecular depigmentation and its correlation with other ocular findings and systemic symptoms.

Methods

We retrospectively reviewed the clinical charts of 53 Japanese patients diagnosed with VKH disease. The scores of trabecular and limbal pigmentation of all patients were recorded. We then examined the correlation between trabecular pigmentation and the presence of sunset glow fundus or skin lesions.

Results

Trabecular pigmentation was significantly lower in the patients with sunset glow fundus than in those without it (P = 0.022), whereas limbal pigmentation showed no significance. However, there were no significant differences in trabecular and limbal pigmentation between the patients with and those without skin lesions. Furthermore, there was no correlation between trabecular and limbal pigmentation.

Conclusions

Depigmentation of the trabecular meshwork develops in some patients in the course of VKH disease. This depigmentation is significantly correlated with sunset glow fundus, but not with limbal depigmentation or skin lesions.     

Unilateral Ocular Manifestations of Vogt–Koyanagi–Harada Disease

Purpose: To describe a case of unilateral Vogt–Koyanagi–Harada (VKH) disease and associated multimodal imaging.

Methods: Retrospective case report.

Results: A 50-year-old Hispanic male presented with three days of painless decreased vision in his left eye, headache, and decreased hearing. His visual acuity was 20/20 in the right eye and counting fingers in the left eye. Examination of his right eye was unremarkable. Funduscopic examination of his left eye revealed multiple serous retinal detachments. Fluorescein angiography demonstrated late multifocal pinpoint hyperfluorescence in his left eye and a diagnosis of VKH disease was made. He was treated with oral prednisone. Serial re-examination demonstrated resolution of the serous retinal detachments and a taper of his oral prednisone was initiated with improvement of his visual acuity to 20/25.

Conclusions: Our patient had imaging and a clinical course that was consistent with VKH disease. This unilateral presentation may represent a clinical variant of VKH disease.     

Vogt–Koyanagi–Harada disease in elderly Japanese patients

PURPOSE: The purpose of this study was to evaluate the characteristics of Vogt-Koyanagi-Harada (VKH) disease in elderly (age > or =65 years) Japanese patients. METHODS: We reviewed the medical records of all patients diagnosed with VKH disease at the Department of Ophthalmology, Oita University Hospital between October 1982 and March 2005. Data extracted included age, gender, prodromal symptoms, visual acuity, ocular manifestations, extraocular findings, human leukocyte antigen (HLA), ocular complications, treatment, and smoldering inflammation. RESULTS: Of the 68 patients with VKH disease, seven (10%) were classified as elderly at onset. The incidence of optic disk hyperemia, choroidal detachment, and cataract was significantly higher in the elderly patients than the non-elderly patients (<65 years). The total dose of corticosteroid used was higher in the elderly. The incidence of smoldering inflammation was more frequent in the elderly. Final visual acuity was preserved relatively well in the elderly. CONCLUSION: The significantly higher incidence of optic disk hyperemia, choroidal detachment, and cataract, and the more frequent smoldering inflammation in elderly VKH patients indicate that special attention should be paid to these parameters in elderly patients.     

Adalimumab Treatment in Patients with Vogt–Koyanagi–Harada Disease

Purpose: To evaluate the clinical outcome and safety of adalimumab in patients with Vogt–Koyanagi–Harada (VKH) disease.

Methods: VKH patients treated with adalimumab seen at the University of Buenos Aires were reviewed. Main outcome measures were visual acuity, anterior segment inflammation, optic nerve inflammation (ONI), steroid sparing effect, number of immunosuppressives, and relapses.

Results: In total, 14 VKH patients, mean age 23.07 ± 8 years; median of adalimumab treatment 10 months, were analyzed. At start of adalimumab treatment (baseline), median of corticosteroid dose was 20 mg and at 6 months, 4 mg. At baseline, 11 patients were on immunosuppressive treatment and at 6 months only four continued with immunosuppressive therapy. In the 28 eyes, the median of active inflammation was 2 at baseline and 0 after 6 months on adalimumab.

Conclusions: Treatment with adalimumab is an effective and safe option, reducing the need for oral corticosteroid and conventional immunosuppressive therapy.     

The spectrum of Vogt–Koyanagi–Harada disease in Iran

Purpose

To report the spectrum of Vogt–Koyanagi–Harada (VKH) disease in Persians.

Materials and methods

This is a retrospective chart review of patients diagnosed with VKH disease at four referral centers in Iran. Patients’ demographics, ocular and extraocular manifestations, treatment modalities, complications, and visual outcomes were collected and analyzed.

Results

Eighty-eight patients with a mean age of 32.1 ± 12.6 years (range 7–79 years) were studied. Fifty-nine patients (67.0%) were female. Sunset glow fundus was seen in 40.9%, and nummular peripheral chorioretinal scars in 55.7% of eyes. Integumentary findings were noticed in 14.8% of the patients. In patients with acute presentation, exudative retinal detachment was the most common ocular finding (87.8%) followed by optic disk swelling (71.4%). Anterior uveitis and vitritis each were found in about half of the studied eyes. Auditory symptoms were reported by 38.8% of the patients. Overall, immunomodulatory agents were used in 72.7% of the patients. Ocular complications occurred in 36.4% of eyes (mean follow-up 3.8 years, range 6–228 months). Final visual acuity was 20/40 or better in 73.3% of eyes. Four patients (4.5%) were classified as having ‘complete’ type of the disease, 36 (40.9%) ‘incomplete’ type, and 48 (54.5%) ‘probable’ type.

Conclusion

In our series, there are clinical features that differ from those reported in other studies. While auditory symptoms occurred in more than one-third of patients, integumentary findings were rather rare. Most patients exhibited the ‘probable’ type of VKH disease. The overall visual prognosis was favorable.

     

Hypothalamic–pituitary–adrenal axis function following intravitreal triamcinolone acetonide injection

To evaluate the pituitary–adrenal axis function by means of the adrenocorticotropic hormone (ACTH) stimulation test following a single intravitreal injection of triamcinolone acetonide (IVTA). Prospective comparative clinical interventional study. Twenty-eight patients (28 eyes) received a single IVTA (4 mg in 0.1 ml) for macular edema. The basal cortisol level and the response to 1 μg adrenocorticotropic hormone stimulation were determined on the morning before IVTA injection and at 1 day and 1, 2, and 4 weeks after IVTA injection. Results were compared with those obtained from a control group of 50 healthy subjects. All patients in the study had normal basal cortisol and normal response to ACTH challenge before receiving IVTA. 1 day following IVTA, basal cortisol was suppressed in one patient in the study group. Fasting serum cortisol levels at 1, 2, and 4 weeks after IVTA injection were normal in all patients in the study group. 1 day following IVTA, the peak response to ACTH at 30 min was blunted in four patients (14.3 % of the study group, p = 0.05) and the cortisol response at 60 min was suppressed (p = 0.009). 1 week following IVTA, the response to ACTH challenge was blunted in only one patient. A single IVTA injection may be associated with impaired hypothalamic–pituitary–adrenal function in some patients during the first 24 h following IVTA.     

Atypical Vogt–Koyanagi–Harada disease or new uveomeningitic syndrome?

Purpose To report on a patient affected by bilateral intermediate uveitis (IU) as the initial sign of an uveomeningitic syndrome.Methods Thorough history, physical examination and ancillary laboratory and radiological testing were performed in this observational case study.Results A 23-year-old Caucasian man developed bilateral IU, primarily diagnosed as idiopathic since a detailed etiologic work-up was not indicative of underlying disease. Seven months later, he presented with poliosis and vitiligo. Lumbar puncture revealed cerebrospinal fluid pleocytosis. Optical coherence tomography showed bilateral subclinical macular edema (ME). The visual acuity was still 20/20 in both eyes. Clinical, laboratory and radiological results did not fit into any known syndrome.Conclusions According to all the tests performed, the disease in our patient is a uveomeningitic disease with IU and ME which could be interpreted as an atypical form of Vogt–Koyanagi–Harada disease or a new uveomeningitic syndrome because there is no evidence for any other known disease.This study received no funding, and the authors had no financial or proprietary interest in it.     

Changes in Scleral Architecture in Chronic Vogt–Koyanagi–Harada Disease

Purpose: To describe scleral changes in chronic VKH.

Methods: Medical records of patients with chronic VKH were retrospectively reviewed. Change of scleral architecture was defined as progressive posterior bowing on OCT, axial length elongation, and/or increased myopia more than –1.0 D, not explicable by other etiologies.

Results: In total, 28 eyes (16 patients) with mean age of disease onset 32.5 ± 14.0 years were included in the study. Disease duration was 15.1 ± 10.2 years. Eight eyes (28.6%) showed progressive scleral architectural changes. Five eyes (18%) developed scleral changes on OCT, not seen on prior imaging (2–12 years earlier). One eye had posterior bowing on OCT with increased axial length, both eyes of a bilateral pseudophake developed increased myopia with increased axial length. Well-circumscribed chorioretinal atrophy within the arcade was associated with progressive scleral change.

Conclusions: Progressive scleral change may develop as a late complication of VKH. The association with well-circumscribed chorioretinal atrophy suggests that chronic choroidal inflammation may be responsible.     

Anterior ischemic optic neuropathy associated with Vogt–Koyanagi–Harada disease

Background

Optic disc swelling is a common finding associated with Vogt–Koyanagi–Harada disease (VKH); however, visual field loss from optic disc involvement is uncommon. This reports report presents recent findings regarding unusual patients with visual field defects from optic disc involvement, thus suggesting the presence of anterior ischemic optic neuropathy (AION) in the acute phase of VKH.

Methods

Observational case series. A consecutive series of 52 patients with VKH (6 complete VKH, 46 incomplete VKH) was reviewed. Fifteen patients in this series had optic disc swelling, and six of them developed irreversible visual field defects in the acute phase of VKH. The clinical features of these six patients were analyzed.

Results

The patients with associated visual field loss were four males and two females between 54 to 79 years of age. They had bilateral panuveitis associated with meningismus. All of the patients had bilateral optic disc swelling and fluorescein angiography showed both a filling delay and late leakage of the optic disc. Visual field examinations revealed various degrees of visual field defects in 11 eyes. They were treated with high-dose corticosteroid therapy, and several weeks later, both the uveal inflammation and optic disc swelling disappeared. The visual fields showed some improvement as the retinal detachments and disc swelling resolved, but the visual field defects remained in ten eyes. The small and localized visual field defects were asymptomatic. Subsequently, optic disc pallor developed in nine eyes and retinal nerve fiber layer thickness, measured by optical coherence tomography, was decreased in six eyes. The fundus gradually showed various degrees of hypopigmentation, but did not show any chorioretinal atrophy causing visual field loss. Four patients had risk factors for AION, including diabetes mellitus or a relatively small optic nerve head.

Conclusions

In this consecutive series of patients with VKH, 15 out of 52 patients were found to have disc swelling, and six patients, who were mostly elderly, had associated visual field loss, which is probably due to AION associated with VKH.     

Comparative study of phacoemulsification–subscleral trabeculectomy versus phacoemulsification–deep sclerectomy

PurposeTo compare the surgical outcomes of phacoemulsification–subscleral trabeculectomy versus phacoemulsification–deep sclerectomy with intraoperative mitomycin C in open-angle glaucoma.MethodsThe study was conducted on 40 chronic primary open-angle glaucomatous eyes with senile cataract. They were divided into two groups: group I (n = 20): eyes undergoing phacoemulsification with subscleral trabeculectomy, and group II (n = 20): eyes undergoing phacoemulsification with deep sclerectomy. Intraoperative mitomycin C (0.4 mg/ml for 3 min) was applied in both groups. Postoperative intraocular pressure (IOP), complications, glaucoma medications, visual outcomes, and the bleb appearance were assessed for 12 months.ResultsThe mean postoperative IOP was significantly lower (P < 0.05) in both groups in all time intervals in comparison to their preoperative values. The mean postoperative IOP was 14.1 ± 5.4 mmHg in group I, and 14.8 ± 3.1 mmHg in group II. No major complications were encountered in either procedure, but complications such as shallow anterior chamber, hypotony, and delayed bleb leaks were common in group I, whereas intraoperative perforation of Descemet’s membrane occurred in group II. No significant difference in visual acuity improvement, visual field changes, and surgical success outcome were found between both groups.ConclusionThere was no significant difference in IOP reduction, surgical complications and visual outcomes between subscleral trabeculectomy, or deep sclerectomy with intraoperative mitomycin C in combination with phacoemulsification and intraocular lens implantations in patients with primary open-angle glaucoma.     

Utility of lumbar puncture in diagnosis of Vogt–Koyanagi–Harada disease

Purpose To determine the significance of lumbar puncture in diagnosis of Vogt–Koyanagi–Harada disease (VKH). Method A retrospective analysis was conducted on 116 consecutive patients diagnosed with VKH. Two additional patients who presented with acute VKH were included in the analysis. Demographic characteristics, including gender, age, and ethnicity, were extracted from the medical record. The stage of disease at presentation was documented. Pertinent laboratory results and diagnostic procedures such as lumbar puncture, fluorescein angiography, and echography that contributed to the diagnosis of VKH were collected. Results Lumbar puncture results for 10 patients were available. Eight of these patients presented with pleocytosis consistent with a diagnosis of VKH. Clinical features and fluorescein angiography confirmed the diagnosis in these patients. Both of the patients who did not exhibit cerebrospinal fluid (CSF) pleocytosis presented with headache, vision loss, and bilateral uveitis. Fluorescein angiography disclosed multiple foci of leakage at the retinal pigment epithelium level with accumulation of dye under the retina and disc leakage, confirming diagnosis of VKH. Conclusion The utility of lumbar puncture as a diagnostic criterion for VKH should be re-evaluated given that clinical features and fluorescein angiography alone often support the diagnosis. The inherent risks and complications associated with the procedure must prompt the clinician to reserve this evaluation for atypical presentations.     

Karl Lindner 1883–1961

Ohne Zusammenfassung