Association between Vogt-Koyanagi-Harada syndrome and HLA-DR1 and -DR4 in Hispanic patients living in southern California.

BACKGROUND: Vogt-Koyanagi-Harada (VKH) syndrome is associated with human leukocyte antigen (HLA)-B54, -DR4, -DR beta 1*0405, -DQ4, and -DR53 in Japanese patients. Disease-associated HLA specificities may differ among races. This study examined HLA associations with VKH syndrome in Hispanic patients living in southern California, a racial subgroup at increased risk for the disease. METHODS: Human leukocyte antigen specificities were determined on 25 Hispanic patients with VKH syndrome and compared with HLA specificities of 217 healthy Hispanic control subjects. Inclusion criteria for study patients were nontraumatic panuveitis with exudative retinal detachments, with or without extraocular manifestations. Tests were performed using standard cytotoxic assays. RESULTS: HLA-DR4 was present in 14 (56%) patients with VKH syndrome and in 62(29%) control subjects (relative risk = 1.96). HLA-DR1 was present in 9 (36%) patients with VKH syndrome and in 19 (9%) control subjects (relative risk = 4.11). HLA-DR1 and DR4 share a common epitope within the DR beta 1 gene. HLA-DR1 and/or DR4 were present in 21 (84%) patients with VKH syndrome and in 76 (35%) control subjects (relative risk = 2.40). CONCLUSIONS: HLA-DR1 and -DR4 were found in a significantly disproportionate number of Hispanic patients with VKH syndrome living in southern California. HLA-DR4, although not HLA-DR1, has been previously associated with VKH syndrome in other groups. These associations suggest a common immunogenic predisposition to VKH among different racial groups, and suggest that a common epitope shared by DR1 and DR4 may be involved in the pathogenesis of the disease.

Trabeculectomy and Molteno implantation for glaucomas associated with uveitis.

PURPOSE: This study compares the outcomes of trabeculectomy and Molteno implantation in the treatment of glaucomas associated with uveitis. METHODS: Forty-five patients with uveitis, who had undergone filtering surgery for glaucomas associated with uveitis, were reviewed retrospectively. Successful outcome was defined as final intraocular pressure (IOP) of 6 to 21 mmHg, with a minimum follow-up of 6 months without visually devastating complications or loss of light perception. RESULTS: One- and two-year life-table success rates, respectively, were 81% and 73% with trabeculectomy (16 patients); 53% and 31% with combined trabeculectomy and first-stage (reserve) Molteno implantation (19 patients); and 79% and 79% with one-stage Molteno implantation (10 patients). In 11 patients who underwent second-stage Molteno implantation after trabeculectomy failure, 1- and 2-year life-table success rates were 79% and 79%, respectively. Complications included surgically treated choroidal effusions (1/45; 2%), choroidal hemorrhages (3/45; 7%), and chronic hypotony (3/45; 7%). Follow-up in all groups ranged from 5 to 70 months (mean +/- standard deviation, 28 +/- 17 months). CONCLUSIONS: Trabeculectomy provides surprisingly good results in glaucomas associated with uveitis (modulation of wound healing with antimetabolites probably would afford an even higher success rate). However, when significant, immediate postoperative and/or moderate chronic postoperative inflammation is likely, aqueous drainage devices appear more likely to control IOP.

Incidence and management of glaucoma in Vogt-Koyanagi-Harada syndrome.

BACKGROUND: The Vogt-Koyanagi-Harada syndrome is a bilateral panuveitis associated with neurologic and dermatologic manifestations. METHODS: The authors reviewed the charts of all patients with Vogt-Koyanagi-Harada syndrome seen at their institution over the past decade to determine the incidence of glaucoma, as well as the results of medical and surgical therapy for glaucoma, in this group of patients. FINDINGS: Of 42 patients diagnosed with Vogt-Koyanagi-Harada syndrome, evidence of glaucoma requiring either medical or surgical intervention occurred in 16 patients (38.1%). Of these, nine (56.3%) had open-angle glaucoma and seven (43.7%) had angle-closure secondary to pupillary block. In 5 (31.3%) of the 16 patients, medical therapy alone was sufficient to control intraocular pressure. Eleven patients (68.7%) required surgical intervention, consisting of laser iridotomy, surgical iridectomy, trabeculectomy with or without 5-fluorouracil, and/or Molteno implantation. CONCLUSION: The relative success of each of these procedures in this group of patients is discussed. Glaucoma is a common complication in the Vogt-Koyanagi-Harada syndrome, and one that is often difficult to control.

Systemic viral infections and their retinal and choroidal manifestations.

Viruses are one of the most common causes of infections involving the posterior segment of the eye. Such infections can occur either on a congenital or an acquired basis, and may affect primarily the retina or the choroid. Congenital cytomegalovirus (CMV) and rubella infections may result in retinitis. CMV retinitis is also the most common cause of acquired viral retinitis, primarily because of the acquired immunodeficiency syndrome (AIDS). Other types of viral retinitis, such as those caused by herpes simplex or herpes zoster, can occur in immunocompromised or immunocompetent individuals. Retinitis or choroiditis caused by viruses such as measles, influenza, Epstein-Barr virus, and Rift Valley fever virus, typically occurs subsequent to an acute viral systemic illness. The systemic and ocular manifestations, as well as the histopathology, laboratory tests, differential diagnoses, and treatment regimens for each of the individual viruses are discussed in detail.

Torulopsis candida (Candida famata) endophthalmitis simulating Propionibacterium acnes syndrome.

Four months after undergoing extracapsular cataract extraction with implantation of a posterior chamber intraocular lens, a 74-year-old woman developed granulomatous anterior uveitis. Although she initially responded well to corticosteroid therapy, she experienced multiple recurrences on discontinuation of this therapy. Slit-lamp examination showed the ocular inflammation to be associated with white cortical material within the lens capsular sac. She underwent removal of the implant as well as the lens capsular sac. Anaerobic culture yielded no organisms, but fungus cultures yielded Torulopsis candida. Histopathologic and electron microscopic studies showed large numbers of yeast sequestered within the lens capsular sac and mild granulomatous inflammation around the sac. Torulopsis candida is occasionally isolated from specimens as a contaminant, but has not yet been shown to produce human disease. The case reported herein documents potential pathogenicity of Torulopsis candida and reveals the importance of organisms other than anaerobic bacteria in causing delayed and localized intraocular inflammation that is virtually identical to Propionibacterium acnes infection.

Repair of retinal detachment caused by cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome.

Twenty-two eyes of 19 patients with the acquired immunodeficiency syndrome who had pars plana vitrectomy and silicone-oil injection after retinal detachment caused by cytomegalovirus retinitis were studied. All patients but one were monitored until time of death. The postoperative survival time and the factors that predicted anatomic success (retinal attachment) and functional success (visual acuity) were analyzed. No intraoperative complications were encountered. The mean survival time after surgery was four months. Of all of the preoperative and intraoperative factors studied, only the duration of cytomegalovirus retinitis was predictive of survival (P less than .03). The anatomic success rate was 89.5% (17 of 19 patients). None of the factors showed a trend or statistical significance in relation to anatomic success. Fifteen of 19 patients (79%) had lost at least two lines of Snellen visual acuity at time of death. Vision declined in a bimodal pattern (within the first postoperative month and after four months postoperatively). The optic nerve was pink and well perfused preoperatively in 16 of 19 patients (81.8%), but optic-nerve atrophy was observed postoperatively in 18 of 19 patients (95.5%). There was a trend for functional success to be influenced by increased intraocular pressure and optic-nerve atrophy, although our sample size was too small for statistical significance.

Anterior uveitis and hypopyon.

We undertook a study to determine the incidence of hypopyon, as well as the most common anterior uveitis entities with which hypopyon is associated. A total of 216 patients with anterior uveitis were studied. The uveitis was acute in 155. Of the 155 patients, 11 (7.1%) had hypopyon. Nine of the 11 patients with hypopyon were positive for HLA B27. Of these nine, two had Reiter's syndrome and one had ankylosing spondylitis; the other six had no confirmed systemic disease. Of the two patients with hypopyon who were HLA B27-negative, one had mixed connective-tissue vascular disease, and one had idiopathic anterior uveitis. Of the 155 patients with acute anterior uveitis, 62 were HLA B27-positive. Thus, the incidence of hypopyon uveitis among HLA B27-positive patients was 14.5% (nine of 62 patients), whereas the incidence among HLA B27-negative patients was only 2.2% (two of 93 patients). These results suggest that HLA B27-related anterior uveitis is the most common cause of hypopyon uveitis, and that most patients with anterior uveitis associated with hypopyon will test positive for HLA B27. Although these results reflect a referral population, they should be of benefit in the treatment of patients with anterior uveitis.

Variations in clinical features of the Vogt-Koyanagi-Harada syndrome.

Forty-eight cases of the Vogt-Koyanagi-Harada (VKH) syndrome occurring in patients residing in southern California were reviewed. Thirty-six patients were Hispanic and 12 of other racial groups. Symptoms of meningismus, predominantly headache, were present in 32 (67%) cases, but the other characteristic neurologic symptoms, i.e., tinnitus and dysacusis, were present in only eight (17%) and six (13%) cases, respectively. Dermatologic changes were rare; vitiligo occurred in five (10%) patients, alopecia in six (13%), and poliosis in three (6%). In this patient population, extraocular signs and symptoms of the VKH syndrome, other than headache, were unusual. The ocular manifestations of the VKH syndrome are more constant and include iridocyclitis, vitritis, diffuse swelling of the choroid, serous retinal detachment, and optic disc hyperemia. Procedures that may aid in the diagnosis include lumbar puncture, fluorescein angiography, and standardized echography. The ophthalmologist must be prepared to make this diagnosis and initiate treatment with high-dose systemic steroids based on the typical ocular findings even in the absence of other (extraocular) manifestations of this disease.

Echographic features of the Vogt-Koyanagi-Harada syndrome.

Vogt-Koyanagi-Harada (VKH) syndrome represents a spectrum of bilateral panuveitis with associated central nervous system and dermatologic manifestations. The diagnosis is based on clinical and angiographic findings, but some of the characteristic features may be either absent or difficult to visualize in the presence of opaque media. With the use of standardized echography (standardized A-scan and contact B-scan echography), we examined nine patients with clear media and clinical evidence of VKH syndrome. Consistent echographic findings included (1) diffuse, low to medium reflective thickening of the choroid posteriorly; (2) serous retinal detachment, located inferiorly or in the posterior pole; (3) mild vitreous opacities with no posterior vitreous detachment; and (4) thickening of the sclera and/or episclera posteriorly. Resolution of these findings occurred with systemic corticosteroid therapy. Standardized echography should be considered an important diagnostic tool in VKH syndrome, especially when visualization of the fundus is poor or when clinical presentation is atypical.

Rapidly progressive outer retinal necrosis in the acquired immunodeficiency syndrome.

Two patients, both seropositive for the human immunodeficiency virus, developed rapidly progressive retinal necrosis associated with a systemic herpes zoster infection. The retinitis in these patients was characterized by primary involvement of the outer retina, with sparing of the inner retina and retinal vasculature until late in the disease process; a rapidly progressive course; poor response to intravenous acyclovir; and development of rhegmatogenous retinal detachment. In one of the patients, the retinitis was initially multifocal. Electron microscopy of a retinal biopsy specimen from one of the patients demonstrated virus particles consistent with a herpesvirus, and polymerase chain reaction disclosed herpesvirus in a retinal biopsy specimen of the other patient. This entity may represent a distinct form of acute retinal necrosis that is seen in immunocompromised individuals.

Pneumocystis carinii choroiditis after long-term aerosolized pentamidine therapy.

Pneumocystis carinii pneumonia is a major cause of morbidity and mortality in patients with the acquired immunodeficiency syndrome. When P. carinii is disseminated, the choroid may be involved and the infection is often fatal. We examined, treated, and followed up two patients who developed choroidal lesions typical of P. carinii while taking aerosolized pentamidine for prophylaxis. The choroidal lesions gradually resolved after three weeks of therapy with intravenous trimethoprim and sulfamethoxazole in one patient, and after three weeks of therapy with parenteral pentamidine in the other patient. The patients did not have clinical or laboratory evidence of P. carinii infection other than in the eye. It thus appears that early ophthalmologic examination may detect disease before it is threatening to sight and allow systemic therapy to be instituted before widely disseminated infection results in a fatal outcome.