Presumed ocular sarcoidosis.

BACKGROUND: Sarcoidosis is a multisystemic granulomatous disease of unknown etiology. Ocular manifestations commonly occur in patients with sarcoidosis, with a granulomatous anterior uveitis as the most-prevalent ocular sign. Acute symptoms of uveitis, such as pain, photophobia, lacrimation, or redness, may be absent. Without early detection and timely treatment, this "silent uveitis" may cause permanent ocular damage. CASE REPORTS: Two patients came in for routine eye examinations, with no symptoms of anterior uveitis. The first, a 36-year-old man, had a bilateral granulomatous anterior uveitis. The uveitis was treated with topical corticosteroids, with no complications. The second case involved a 44-year-old woman with chronic, recurrent, bilateral, non-granulomatous anterior uveitis. Despite treatment with topical and oral corticosteroids. the patient had a prolonged course with recurrent episodes leading to secondary sequelae, including glaucoma and cataract. Both patients were co-managed with internal medicine, and in each case, systemic workups were consistent with sarcoidosis. CONCLUSION: Anterior uveitis often manifests as the initial presentation of sarcoidosis. Without acute symptoms, the detection and diagnosis may be delayed, leading to visual deterioration. The diagnosis of sarcoidosis may be difficult, owing to the lack of definitive diagnostic criteria and a variety of presentations. Histologic confirmation may not always be possible or practical. However, a range of serological and radiological tests, when combined with physical and ophthalmic evaluation, can lead to the presumed diagnosis of sarcoidosis. Aggressive treatment is imperative in order to prevent permanent structural damage to the eye resulting from this idiopathic inflammation.     

Unusual ocular presentation of sarcoidosis.

A patient is presented with a probable sarcoid granuloma involving the surface of the optic disc. Systemic steroid administration resulted in a resolution of the fundus changes and return of normal vision. Although ocular sarcoidosis is usually manifested by anterior segment inflammation, it is apparent that it may also produce proliferative lesions of the optic nerve.     

Diagnosis of ocular sarcoidosis by diagnostic criteria for systemic sarcoidosis

PURPOSE: To evaluate the diagnostic criteria for systemic sarcoidosis in diagnosis of ocular sarcoidosis. SUBJECTS AND METHODS: Subjects were 105 ocular sarcoidosis suspects and 37 patients with other uveitis. We diagnosed ocular sarcoidosis suspects using the diagnostic criteria for systemic sarcoidosis proposed by the Japanese Committee for Diffuse Lung Diseases. The criteria included histological and clinical diagnosis, and the clinical diagnosis required 5 systemic tests: 1) tuberculin skin test, 2) serum gamma-globulin(gamma-gl), 3) serum angiotensin converting enzyme(ACE), 4) serum lysozyme, and 5) 67Ga scintigraphy. Three positive findings including either 1) or 3) fulfilled the clinical diagnosis. RESULTS: Sixty-two patients were histologically and/or clinically diagnosed, and 43 patients remained undiagnosed. The histological and clinical diagnosis did not produce the same diagnostic yields. The sensitivity of ACE and gamma-gl was low. The percentage of patients showing increased lymphocytosis and/or CD 4/8 in bronchoalveolar lavage was similarly high in the diagnosed and undiagnosed, suggesting the presence of definitive ocular sarcoidosis in the undiagnosed. CONCLUSIONS: The diagnostic criteria for systemic sarcoidosis yielded false negative results in diagnosing ocular sarcoidosis. The selection and combination of systemic tests for clinical diagnosis should be further studied.     

Assessment of blood flow in orbital arteries in ocular sarcoidosis

PURPOSE: Posterior uveitis in ocular sarcoidosis is characterized by obliterative arteriolitis, so-called "microangiopathy", in sarcoidosis that may affect blood flow in ocular arteries. This study was performed to evaluate blood flow velocity in orbital arteries in patients with ocular sarcoidosis. METHODS: This study is a case-control study. Thirty-two patients with posterior uveitis diagnosed on the basis of pathological or clinical findings as having ocular sarcoidosis functioned as cases and 24 healthy volunteers as controls. Pulse rate and blood flow velocities were measured in central retinal arteries, ophthalmic arteries, or short posterior ciliary arteries by the pulsed Doppler method. Laser flaremetry was also performed. Blood flow velocities were compared in patients with sarcoidosis and controls and the correlation coefficients between flare intensity values and flow velocities were evaluated using Student's t-test. RESULTS: Blood flow velocities in orbital arteries in eyes with sarcoidosis were significantly lower than those in normal eyes. The resistance index (RI) of peripheral vessels, which is calculated as (maximal velocity - minimal velocity)/maximal velocity, was significantly higher in patients with sarcoidosis. No association was found between flare intensity values and flow velocities. CONCLUSIONS: Patients with ocular sarcoidosis have impairment in ocular circulation. We speculate that changes in orbital blood flow resulted from inflammatory changes in fundus vasculature.     

Pediatric ocular sarcoidosis

Sarcoidosis is an uncommon cause of childhood uveitis. However, the ophthalmologist familiar with the clinical features of childhood sarcoidosis can play a key role in the diagnosis and treatment of this disorder. Two subsets of pediatric sarcoidosis are identified. The 8-15 year age group has almost universal lung involvement, with the eye, skin, liver, and spleen involved in 30-40% of cases. Children 5 years of age and under are characterized by the triad of uveitis, arthropathy, and skin rash. The epidemiology, clinical features, diagnostic evaluation, and ocular management of pediatric sarcoidosis are reviewed. The clinical and laboratory findings that distinguish sarcoidosis from other causes of childhood uveitis are discussed.     

Immunopathology of ocular sarcoidosis

Summary Sarcoidosis is a multisystem disease characterized by enhanced immune responses at sites of involvement. To elucidate the immunopathogenesis of ophthalmic lesions, cell infiltrates in biopsies from conjunctiva and other tissues involved (lungs, lymph nodes, skin) were studied in 26 patients with active sarcoidosis in order to define the surface phenotype and the distribution of cells in granulomatous lesions. Biopsy specimens were also stained for detection of immunoglobulins, complement and fibrinogen deposits. The data demonstrate a lymphocytes/macrophages interaction in the central core of granulomatous areas as the crucial event that initiates the maintains the state of inflammation: at all sites of disease activity is present a compartmentalization of T-cells expressing a helper-related phenotype which account for the great majority of infiltrating cells both in the early lesions (aggregate of macrophages surrounded by lymphocytic infiltrate) and in well-organized sarcoid granulomata. The presence of plasma cells and immunoglobulin deposits may represent an epiphenomenon in line with the helper infiltration, suggesting a local hyper-reactivity of the B-cells immune system. This study suggests some immunopathogenetic mechanisms leading to the formation and growth of conjunctival sarcoid granulomata.     

Diagnosis of ocular sarcoidosis

INTRODUCTION: Sarcoidosis is a chronic inflammatory disorder with an unknown etiology characterized by noncaseating granulomas. The disorder is a multisystemic disease and affects many organs, including most often the lung, lymph nodes, skin, heart, liver, muscles, and the eye. MATHERIAL AND METHODS: Based on a review of the literature and on an algorithm generated in an international workshop on sarcoidosis, this article provides the reader with a schematic and simple approach to the diagnosis of ocular sarcoidosis. CONCLUSIONS: In a considerable proportion of cases it is the ophthalmologist who first sees patients presenting with the ocular expression of sarcoidosis. In countries where the incidence of sarcoidosis is common, like Japan, a complete workup should be performed, whereas in countries where the incidence of the disease is less high, a noninvasive approach may be warranted at first.     

Interferon-alpha-associated presumed ocular sarcoidosis

Background  Interferon alpha, used in the treatment of different viral, autoimmune and malignant diseases, is known to induce a variety of side effects. Recently, induction of sarcoidosis during interferon therapy has been reported. We analyzed patients for uveitis, possibly induced by interferon alpha. Methods  We report on three patients who had developed typical signs of ocular sarcoidosis under treatment with interferon alpha for chronic hepatitis C virus infection. In two patients, conventional interferon alpha was used and in another one, pegylated interferon alpha-2b. All patients additionally received ribavirin. Results  In all three cases, panuveitis was diagnosed. The mean duration of interferon treatment before development of uveitis was 10 months. Clinically, all patients demonstrated granulomatous panuveitis with choroidal granulomas of various sizes. In one case, the uveitis developed together with renal failure, fever and malaise. In this patient, an elevated ACE level was detected. In another patient, the diagnosis of sarcoid induced uveitis was confirmed by positive chest CT scan. The intraocular inflammation was managed with a reduction of the interferon dosage. The therapy with ribavirin was not changed. All patients received topical steroids. Systemic steroids were applied only in the case with systemic disease manifestations. Conclusions  Uveitis can be a sign of sarcoidosis induced by interferon alpha. Further studies are required to support the observation that with early diagnosis the prognosis of uveitis seems to be good.     

Validation of international criteria for the diagnosis of ocular sarcoidosis proposed by the first international workshop on ocular sarcoidosis

Purpose  

To validate the international criteria for the diagnosis of ocular sarcoidosis as proposed by the First International Workshop on Ocular Sarcoidosis (FIWOS).     

Risk factors for ocular sarcoidosis

We reviewed 121 consecutive patients with biopsy-proven sarcoidosis who visited the sarcoidosis clinic of the University Hospital in Amsterdam, to determine the risk factors for the development of ocular manifestations. Of 121 patients 52 (43%) were black. Ocular disease developed in 50 (41%) patients and was more common in female and in black patients. Uveitis was the most frequent manifestation of ocular sarcoidosis (29 out of 50 or 58%). There were no differences in the extra-ocular manifestations of the sarcoidosis between patients with and without ocular disease or between uveitis and non-uveitis patients. This study covered a mixed racial population and shows that different types of uveitis are seen in white and black patients. Anterior uveitis was more frequent in black patients (P < .001), whereas posterior uveitis was more common in white patients (P < .01). Chronic posterior uveitis with complications occurred most frequently in white female patients with late onset of the systemic disease. Uveitis was an early feature of sarcoidosis (25 out of 29 or 86%); moreover in 9 out of 29 (31%) cases, uveitis preceded the non-ocular detectable signs of sarcoidosis by more than one year. This emphasizes the importance of periodic re-evaluation of uveitis patients for sarcoidosis.     

Unusual clinical and histopathological findings in ocular sarcoidosis.

A 37-year-old Caucasian woman presented with a blind left eye and granulomatous panuveitis in the right eye. There was a subretinal neovascular membrane with haemorrhage beneath the macula and widespread subretinal lesions that were interpreted as choroidal granulomas in the right eye. A chest x-ray that showed diffuse pulmonary fibrosis without hilar lymphadenopathy was the only contributory clinical finding. Systemic and subconjunctival steroids and photocoagulation to the right macula brought about temporary remission. The painful left eye was enucleated. Histopathological examination revealed diffuse, noncaseating granulomas in the iris and ciliary body, retina, choroid, optic nerve, sclera and scleral emissaria, and inferior oblique muscle. A preretinal membrane was studied by electron microscopy. It was composed of a collagenous matrix containing fibroblasts and fibrous astrocytes. Some vessels, surrounded by a multilaminar basement membrane, revealed many features of normal retinal vasculature. Others were lined by markedly attenuated endothelial cells with occasional "open' junctions and fenestrations.     

Course and outcome of ocular sarcoidosis

In a series of 281 patients with histologically confirmed sarcoidosis, 79 initially had ophthalmic sarcoid manifestations. Of 22 patients with uveitis, 21 were seen regularly as long as the inflammation was active, and 71 of the 79 patients (90%) underwent a follow-up study five to 16 years (mean, nine years) later and using the same protocol. In the 21 patients with uveitis, the disease exhibited either a monophasic course (eight patients) with favorable visual outcome or a relapsing course (13 patients) with severe visual loss in five eyes. Thirty-three patients showed chronic ophthalmic changes at the follow-up examination, including conjunctival granulomas (13 patients), lacrimal gland involvement (22 patients), uveitis (four patients), and involvement of lacrimal passages (three patients). In 15 of these 33 patients, the general physical examination and the chest x-ray showed no evidence of systemic sarcoidosis. However, the serum angiotensin converting enzyme level was increased in a significantly greater proportion of these 15 patients than in the patients assessed as totally recovered from sarcoidosis.     

Retinal macroaneurysm associated with ocular sarcoidosis

Purpose  

To characterize retinal macroaneurysm, which although rare, has been reported as a specific complication of ocular sarcoidosis.     

Ocular hypertension associated with ocular sarcoidosis

PURPOSE: To report bilateral ocular hypertension in association with ocular sarcoidosis. METHODS: Case note review of patients with a diagnosis of sarcoidosis-related uveitis. RESULTS: The authors identified 5 patients who fulfilled the diagnostic criteria for ocular sarcoidosis and who had intraocular pressures of > 40 mmHg in each eye. CONCLUSIONS: Physicians should be aware of the association of raised intraocular pressure with ocular sarcoidosis.