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[Incidence of ocular manifestations in patients with histologically confirmed systemic sarcoidosis].

BACKGROUND: Intraocular findings in sarcoidosis were described by US studies with 35 % anterior uveitis, 25 % posterior uveitis and 20 - 30 % for late complications in case of first presentation. We report on the spectrum and diagnostic possibilities in 38 German patients. PATIENTS AND METHODS: 38 patients (68 eyes) aged 11 - 58 years (average 42.7 y), who suffered of intraocular manifestations in histological confirmed systemic sarcoidosis (1987 - 1997), were completely evaluated retrospectively. For additional diagnostic tools fluorescein angiography, optical coherence tomography, nuclear magnetic resonance tomography and measurements of angiotensin-converting enzyme, lysozyme and calcium in serum were performed. RESULTS: 15 patients (22 eyes = 32.4 %) had anterior uveitis: granulomatous keratouveitis (10 eyes), granulomas of the iris (6), granulomas of the trabecular meshwork (3) and 22 patients (42 eyes = 61.8 %) an intermediate and posterior uveitis: granulomatous perivasculitis (18 eyes), cystoid maculopathy (8), pars planitis (6), neuroretinitis (4), optic neuritis (3), choroiditis (3). Late complications in case of first presentation were found in 22 patients (39 eyes = 57.4 %): posterior synechiae 14 x, secondary glaucoma 10 x, cataracta complicata 8 x, optic atrophy 6 x, intraocular calcification 1 x. CONCLUSION: Compared to previous studies with heterogeneous ethnic composition, intraocular inflammations with confirmed sarcoidosis in German patients show more than 60 % involvement of the posterior segment. We may speculate on the reasons for these discrepancies as being due to ethnic reasons, age and long-term follow-up. In case of typical ocular signs of sarcoidosis, treatment should be started immediately even without histological confirmation. In some cases histological confirmation is successful 8 years after first presentation.

Adolescent↗

[Semiology and classification of uveitis].

Defined as an intraocular inflammation, uveitis may be linked to a systemic disease or represent an isolated entity. Screening for associated extra-ocular manifestations is mandatory in uveitis patients. The localisation of inflammation may be uni- or bilateral, anterior, intermediate or diffuse (panuveitis). Other main elements of the evaluation are the acute or chronic mode and the detection of a granulomatous presentation. In some cases, the examination of intraocular structures may be enough for the diagnosis of uveitis. When a correct approach is taken to the diagnosis of uveitis, causes are identified in approximately 50% of cases and presumed in 25% of patients; in one-fourth of cases, the origin of inflammation remains idiopathic.

Adult↗

[Vision-threatening complications in childhood uveitis].

PURPOSE: We analyzed the epidemiologic data and vision-threatening complications in different forms of childhood uveitis. METHODS: This retrospective study included 187 consecutive patients with onset of uveitis before the age of 16 years classified as anterior (AU), intermediate (IU), posterior (PU), and panuveitis (PanU). We analyzed the epidemiologic data as well as visual acuity, uveitic complications and the conservative and surgical therapy. RESULTS: Associated disease was observed in 85 of 187 patients. The most common complications in AU patients were cataract, posterior synechiae, band keratopathy and CME. IU was accompanied by dense vitreous opacities, cataract and CME. Macular scars were the most frequent cause for visual loss in PU. PanU was complicated by dense vitreous opacities, cataract, retinal detachment, CME and phthisis bulbi. CONCLUSIONS: Childhood uveitis is frequently associated with systemic immune-mediated diseases. The diverse uveitis types have different but typical complications.

Adolescent↗

[Intraocular non-Hodgkin's lymphoma and its therapy-- a case series of ten patients].

BACKGROUND: The timely and correct diagnosis of intraocular non-Hodgkin's lymphoma represents a huge challenge to clinicians. Two thirds of intraocular lymphomas are a manifestation of a primary CNS lymphoma (PCNSL) arising outside the lymphatic system and are localized in the brain, the meninges or the spinal chord. Ten to twenty percent commence as vitreous or retinal infiltrates mimicking uveitis. Ninety five percent of PCNSL are B cell lymphomas. PATIENTS: Three exemplary cases from a group of ten patients treated between 1998 and 2002 are presented. A table provides a summary of the relevant details of all ten patients. RESULTS: The mean age at presentation was 63.5 years with a female to male ratio of 6 to 4. Nine patients were diagnosed as having intermediate or posterior uveitis, in one patient choroidal metastases were suspected. Six patients had a concomitant CNS lesion while four patients showed isolated intraocular lymphoma only. The presence of a highly malignant B cell lymphoma was proven by vitreous biopsy in nine cases and by stereotactic biopsy of a CNS lesion in one patient. All patients were treated by intravenous chemotherapy, however, no binding recommendations with regard to treatment exist to date. CONCLUSIONS: We give an overview of all current treatment regimens and their pitfalls. At present it is recommended that all patients with proven PCNSL be entered in a multicenter randomized study under the auspices of the Department of Internal Medicine III of the Benjamin-Franklin-University-Hospital, Berlin and the Department of Neurology of the University Hospital of Tuebingen.

Aged↗

Genetic heterogeneity in uveitis.

Eighty-nine unrelated patients with ocular inflammation (uveitis) were investigated for the HLA class I and class II genetic markers, We subdivided our patients according to: 1. the anatomical location of the lesion; 2. the temporal course of the disease; 3. the aetiology. We eliminated from our sample of patients the individuals with other systemic diseases. We could not find an association with B27, as previously described, but we did note statistically significant differences between the class II antigen distribution in the different anatomical subgroups. HLA-DR3 seems a marker of the intermediate form of uveitis (p, uncorrected 0.03); the absence of DR1 in the patient group with posterior uveitis may be a protecting factor (p. uncorrected less than 0.01); the presence of DR4 in all cases of panuveitis is statistically significant (p, uncorrected = 0.0006).

Adolescent↗

Ocular manifestations and treatment of syphilis.

Syphilis is a sexually transmitted, chronic, systemic infection caused by the spirochete Treponema pallidum. If left untreated, the disease progresses through four stages, with the potential to cause significant morbidity to any major organ of the body. Frequent syphilitic ocular manifestations, which can occur at any stage of the disease, include interstitial keratitis, anterior, intermediate, and posterior uveitis, chorioretinitis, retinitis, retinal vasculitis and cranial nerve and optic neuropathies. Diagnosis is centered around a high level of clinical suspicion and includes treponemal specific and non-treponemal serologic tests. All patients with newly diagnosed syphilis should be tested for co-infection with human immunodeficiency virus, as the risk factors are similar for both diseases. Additionally, all patients with ocular syphilis should be tested for neurosyphilis. The preferred treatment for all stages of syphilis remains parenteral penicillin G. With proper diagnosis and prompt antibiotic treatment, the majority of cases of syphilis can result in a cure.

Anti-Bacterial Agents↗

[Humoral and cellular immune responses to retinal S-antigen in uveitis patients].

Humoral and cellular immune responses to purified S-Ag were determined in 73 patients with anterior-, intermediate- and pan-uveitis and in 55 healthy subjects by ELISA and leucocyte migration inhibition test. The positive rates of humoral immune response to S-Ag in patients and controls were comparable; however, the positive rate of cellular immune response to S-Ag in the patients (54.6%) was significantly higher than that in the controls (3.3%), and that in pan-uveitis patients (69.4%) was significantly higher than in patients with anterior uveitis (15.4%), highly suggesting that the cellular immune response to S-Ag was involved in the onset of uveitis, especially when the choroid and retina were affected. The breakdown of anterior chamber associated immune deviation and abnormal expression of intraocular MHC-II antigens may contribute to the development of cellular immune response. More studies are needed.

Adolescent↗

Uveitis associated with childhood rheumatic diseases.

Optimal management of childhood rheumatic diseases requires an appreciation of their multisystem nature. The eye represents an important site of involvement, and inflammation of the uveal tract is a particularly frequent and potentially debilitating extra-articular feature of some childhood rheumatic diseases. Anterior uveitis associated with oligoarticular juvenile idiopathic arthritis is an especially distinctive entity. Other disorders in children, however, can be associated with posterior and intermediate uveal tract inflammation. The potentially debilitating consequences of uveitis associated with childhood rheumatic diseases, the inadequacies of existing therapies, and the immunopathogenic basis for particular forms of uveitis have prompted the use of immunomodulatory therapy, including new biologic agents, to treat childhood uveitis. This review summarizes recent contributions to the literature that help to clarify the spectrum of conditions associated with uveitis in children, consider evidence for immunopathogenic processes associated with uveitis, and address new approaches to therapy.

Adjuvants, Immunologic↗

Seasonal variation of endogenous uveitis in south-western Finland.

PURPOSE: To evaluate if there is a seasonal pattern to the incidence of endogenous uveitis in south-western Finland with special reference to acute anterior uveitis. METHODS: The incidence rates per month of the 414 new uveitis cases from years 1980-82 and 1988 in the district of Turku University Hospital were calculated. The months of the year were grouped into warm (June to September), transitional (April, May, October, November), and cold (December to March) seasons based on the mean air temperature of the months in Turku. RESULTS: We observed a statistically significant increase in the incidence of all uveitis cases in the warm and transitional seasons compared with the cold season (p=0.030 and p=0.008 respectively). A similar seasonal trend was found among anterior uveitis cases, but not among the intermediate, posterior or panuveitis cases. The incidence of acute anterior uveitis cases was higher in the transitional than in the cold season (p=0.025). No seasonal variation of the incidence was found in the subgroup of acute anterior uveitis where ankylosing spondylitis had been confirmed (p=0.70). CONCLUSION: The present data suggests that there is seasonal variation of the incidence of uveitis in south-western Finland.

Acute Disease↗

Ocular lesions in 200 patients infected by the human T-cell lymphotropic virus type 1 in martinique (French West Indies).

PURPOSE: To describe the ophthalmologic features observed in patients infected by the human T-cell lymphotropic virus, type 1 (HTLV-1) in Martinique (French West Indies). DESIGN: Prospective consecutive observational case series. METHODS: A complete ophthalmic examination was performed. PATIENTS: Of 200 patients infected by HTLV-1, 77 (38.5%) were seropositive and 123 (61.5%) had HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). RESULTS: Uveitis was found in 29 cases (14.5%). Symptoms were mild and the uveitis had little effect on visual function. Ten cases of uveitis were discovered through a systematic examination and had no ocular symptoms. Most of the uveitis was anterior or intermediate. The lesions responded to corticosteroid therapy, but tended to recur. Keratoconjunctivitis sicca existed in 74 patients (37%), accompanied by lymphoplasmocytoid infiltration of the secondary salivary glands rated 3 or 4 on the Chisholm scale in nearly 50% of cases. Corneal alterations were observed in 20 cases (10%), and alterations in the retinal pigment epithelium in 3 cases. CONCLUSION: The three types of ocular affections seen most frequently were uveitis, keratoconjunctivitis sicca, and interstitial keratitis. In patients with HAM/TSP, uveitis was more frequent among younger patients, patients with earlier onset of HAM/TSP, and patients with severe motor disability. Because uveitis is related to a high intrathecal production of immunoglobulin, it could represent a marker for severity of HTLV-1 infection with respect to the course of HAM/TSP. The sicca syndrome related to HTLV-1 virus differs from primary or secondary Sjögren syndrome, because it does not reveal any of the immunologic anomalies generally seen in this disease. Interstitial keratitis was more frequent among patients with HAM/TSP who had high proviral DNA levels.

Adult↗

Mycophenolate mofetil is a highly effective and safe immunosuppressive agent for the treatment of uveitis : a retrospective analysis of 106 patients.

BACKGROUND: We evaluated the outcomes of patients with different forms of chronic uveitis treated with mycophenolate mofetil (MMF) as an immunomodulatory and steroid-sparing agent. The multi-system side effects that arise after long-term treatment with corticosteroids and other immunosuppressants prompted us to use MMF. MMF is a selective inhibitor of inosine monophosphate dehydrogenase, thus blocking purine synthesis via the de novo pathway preferentially used by T and B lymphocytes. METHODS: Between 1998 and 2003, 106 patients were treated for uveitis (anterior n=26, intermediate n=51, posterior n=23, panuveitis n=6) with MMF at a dose of 1g twice daily. Treatment duration was at least 6 months (n=10), in most cases greater than 12 months (n=77) and in 25 cases between 24 months and 41 months, when the present retrospective evaluation was undertaken. Patient charts were analysed according to a standardized evaluation protocol. RESULTS: In 95 patients MMF was combined with prednisolone at a dosage of 2.5-10 mg per day. In 8 patients MMF was used as a monotherapy, and in 3 cases one further systemic immunosuppressant was required. The number of recurrences during MMF treatment was none or one in 92 patients, two in 6 cases and three or more in 8 patients. In none of the patients had MMF been stopped at the time of data analysis. The most frequently observed side effects were gastrointestinal upset (15%), followed by headache (9.3%), fatigue (5.7%), eczema (5%), and hair loss (3.5%). Other side effects were sporadic. Most of these phenomena were transitory. Forty-two patients experienced no side effects at all. In 4 patients MMF was judged ineffective due to failure to reduce the number of recurrences of severe inflammation compared with the previous therapeutic regime, or indeed occurrence of persistent macular oedema. CONCLUSIONS: Our results show that MMF is an effective immunosuppressant in patients with uveitis. We provide evidence that MMF controls the disease in the majority of patients with an acceptable profile of side effects.

Adolescent↗

HLA-B27 typing in the categorisation of uveitis in a HLA-B27 rich population.

AIMS: To determine whether HLA-B27 typing helps the clinician in the diagnostic examination of uveitis in a HLA-B27 rich population and also whether the clinical picture of HLA-B27 positive unilateral acute or recurrent anterior uveitis (AAU) is distinguishable from the idiopathic negative form. METHODS: During a 3 year period 220 consecutive patients with undetermined uveitis at onset were examined in the Helsinki University Eye Clinic. HLA-B27 antigen was tested for 85% of the patients. Other laboratory or x ray examinations were performed on the basis of the anatomical classification of uveitis and the biomicroscopic features characteristic of uveitis associated systemic diseases. RESULTS: HLA-B27 antigen was found significantly more often in patients with anterior (71%) and acute/recurrent unilateral (79%) uveitis than in patients with intermediate, posterior panuveitis (7%), and chronic (7%) or bilateral (12%) forms. Of the 16 cases of HLA-B27 negative unilateral AAU, five showed biomicroscopic features representing uveitis entities. The remaining 11 cases did not differ in any respect from the cases of HLA-B27 positive unilateral AAU. CONCLUSION: HLA-B27 antigen helps the clinician in the diagnostic examination of unilateral AAU. Positive test results serve as a clue to search for spondyloarthropathies, and negative results indicate the need to look for specific uveitis entities and other systemic diseases. The occurrence of HLA-B27 positivity in conjunction with uveitis entities other than unilateral AAU is of the same level or less than in the population of Finland in general.

Acute Disease↗

Analysis of pediatric uveitis cases at a tertiary referral center.

OBJECTIVE: To analyze demographics, anatomic data, diagnoses, systemic associations, and visual outcomes of pediatric patients in a large tertiary eye center. DESIGN: Retrospective cohort study. METHODS: The records of 1242 patients with uveitis referred to the Ocular Immunology and Uveitis Service of the Massachusetts Eye and Ear Infirmary (MEEI) from 1985 to 2003 were reviewed retrospectively. Two hundred sixty-nine patients 16 years and younger were identified. RESULTS: Among 269 children with uveitis, 53.5% were girls, 82% were Caucasian, and 82% were born in the United States. Mean age was 8 years (standard deviation, 3.8; range, 1-16). Anterior uveitis represented 56.9% of cases; intermediate, 20.8%; panuveitis, 16%; and posterior, 6.3%. Nongranulomatous (77.6%) and noninfectious (85.7%) were the most frequent types of inflammation. The process was bilateral in 74.4% of patients. Mean follow-up was 22 months, with mean age of 8 years at diagnosis. Mean duration of uveitis at the time of presentation at the MEEI was 2 years. The range of time between the diagnosis of uveitis and referral was 1 day to 5.6 years. The length of time between diagnosis of uveitis and the referral to the tertiary center strongly correlated with the complication rate and degree of visual impairment in our study. The longer the time before the patients were seen by the uveitis expert, the worse the visual outcomes. No systemic associations were found in 58% of patients, juvenile idiopathic arthritis was responsible for 33% of cases, 8% of patients had other systemic associations, and 1% had tubulointerstitial nephritis uveitis syndrome. CONCLUSIONS: Uveitis remains a serious cause of morbidity and visual loss in children. Timely referral to uveitis specialists in the tertiary referral centers may lead to improved visual outcomes in children with chronic uveitis.

Acute Disease↗

A randomized, masked, cross-over trial of acetazolamide for cystoid macular edema in patients with uveitis.

PURPOSE: To study the effect of acetazolamide on cystoid macular edema in patients with uveitis. METHODS: Forty patients with chronic intermediate, posterior, or panuveitis associated cystoid macular edema were randomized into a masked, cross-over trial comparing acetazolamide versus placebo. Patients received an initial 4-week course of either acetazolamide or placebo (course A) followed by a 4-week washout period. They then received a 4-week course of the opposite study medication (course B). Primary endpoints included area of cystoid macular edema measured on late-phase views of fluorescein angiography and visual acuity. RESULTS: Thirty-seven patients completed the trial and were available for analysis; 17 (46%) were randomized to receive acetazolamide and 20 (54%) to receive placebo during course A. Acetazolamide resulted in a 0.5-disc area (25%) decrease in cystoid macular edema over that of placebo (P = 0.01; estimated treatment effect = -0.5 disc areas; 95% confidence interval, -0.9 to -0.1). However, there was no statistically significant effect of acetazolamide on visual acuity (P = 0.61; estimated treatment effect = 0.6 letters; 95% confidence interval, -2 to 3). CONCLUSIONS: A 4-week course of acetazolamide therapy results in a statistically significant but small decrease in cystoid macular edema in patients with chronic uveitis, and does not improve visual acuity. In contrast to previous studies in the literature, acetazolamide may have a more limited clinical benefit in patients with long-standing cystoid macular edema associated with chronic uveitis.

Acetazolamide↗

Schematic interpretation of indocyanine green angiography in posterior uveitis using a standard angiographic protocol.

OBJECTIVE: Indocyanine green angiography (ICGA) detects fluorescence produced by the ICG molecule in the near infrared wave lengths showing choroidal vascular structures. Indocyanine green angiography may prove useful in the workup of uveitis with choroidal involvement. The authors' purpose was to test a standardized ICGA protocol for posterior uveitis to gather systematic and comparable data and to design a schematic approach for the interpretation of angiographic signs. DESIGN: The proposed ICGA procedure included the search for preinjection fluorescence. In the early phase of ICGA (until +/- 2-3 minutes postinjection), posterior pole frames were taken to detect abnormalities in the retinal and choroidal arteriovenous circulation patterns. During the intermediate phase (12 +/- 3 minutes), posterior pole frames and eight 360 degrees panorama frames were taken to detect fluorescence abnormalities in the background impregnation of the choroid, the same sequence being repeated in the late phase (40 +/- 10 minutes). A cohort of more than 300 patients was analyzed in this standard fashion in 2 centers. PARTICIPANTS AND MAIN OUTCOME MEASURE: Determination of ICGA features and the proposed schematic approach for ICGA interpretation were based on the analysis of 109 cases of posterior uveitis with a well-determined diagnosis. RESULTS: For uveitis, the intermediate and late phases of ICGA were found to yield the most valuable information showing either ICG hyperfluorescence or hypofluorescence or both. The ICG hyperfluorescence, always reflecting increased leakage or staining but not window defects because there is no pigment epithelium screen in ICGA, could originate either from increased leakage of the choriocapillaris, the large choroidal, or the retinal vessels. The characteristic ICG hypofluorescent dark dots indicating impairment of physiologic impregnation of the choroid could take at least five different patterns. CONCLUSION: To date, ICGA features still are difficult to interpret. The proposed standardized ICGA protocol and schematized interpretation for posterior uveitis will help determine ICGA semiology for these disorders and might give new insights into their pathophysiology.

Choroid↗

Results of extracapsular cataract extraction with intraocular lens implantation in eyes with uveitis and Fuchs' heterochromic iridocyclitis.

A total of 63 cataractous eyes of 48 patients (group 1) with uveitis and 12 eyes of 12 patients (group 2) with Fuchs' heterochromic iridocyclitis underwent extracapsular cataract extraction (ECCE) with capsular bag fixation of a posterior-chamber intraocular lens (PC OIL). A perioperative regimen of systemic dexamethasone (0.8-1.5 mg/kg) was initiated. This dose was tapered by 20 mg/day, reaching zero within 4-8 days. Intraoperatively, synechiolysis was required in 51 of 63 eyes in group 1 and a sector iridectomy was necessary in 42 eyes. A fibrinous reaction occurred in 7 eyes. During a mean follow-up period of 2 years, 7 eyes developed uveitis recurrences that were successfully treated with topical and systemic steroids in 4 eyes; the other 3 eyes developed cystoid macular edema. Overall, mean visual acuity improved from 20/120 to 20/50. Intraoperatively, 3 patients in group 2 developed a transient hemorrhage from atypical anterior-chamber-angle vessels. Postoperatively, 3 eyes showed a transient fibrinous reaction. The mean visual acuity improved from 20/240 to 20/30. In patients with Fuchs' heterochromic iridocyclitis, ECCE with PC IOL implantation renders good intermediate results. In other selected patients with uveitis, in-the-bag IOL implantation may be performed with an acceptable risk. As judged from their improved visual acuity, 57 of 63 eyes (90.5%) benefited from the procedure.

Adult↗

The tuberculin skin test in the diagnosis of tuberculous uveitis.

Of 18 patients (seven men and 11 women, ranging in age from 15 to 63 years) with presumed tuberculous uveitis seen between 1970 and 1982, 11 had intermediate-strength tuberculin skin test responses of less than 10 mm of induration. Similarly, nine had intermediate-strength responses of less than 5 mm of induration. Thus, any response of erythema or induration may be significant in the diagnosis of tuberculous uveitis and evidence enough for further testing with an isoniazid therapeutic trial.

Adolescent↗

[Uveitis: an etiological study of 200 cases following a protocol].

BACKGROUND: To evaluate the usefulness of a systematic study of patients with uveitis and to assess the associated systemic diseases. METHODS: 200 patients seen in an outpatient clinic for the evaluation of uveitis between 1981 and 1988 were included in the study. Patients with eye disease associated with drug abuse or human immunodeficiency virus were excluded. The study protocol included an initial clinical and ophthalmological evaluation followed by selected specific investigations. RESULTS: Anatomical localization: anterior uveitis 122 (61%), posterior 41 (20.5%), panuveitis 30 (15%) and intermediate 7 (3.5%). ETIOLOGY: 74 cases (37%) were secondary, 101 (50.5%) were idiopathic, and 25 (12.5%) were specific syndromes of uveitis of unknown cause. Toxoplasmosis was the most common cause of infective uveitis, and ankylosing spondylitis was the most common noninfective cause. Diagnostic process: group 1, diagnosed by the ophthalmological investigation (25 cases); group 2, diagnosed on the basis of the accompanying clinical features and/or specific investigations (66 cases); and group 3, diagnosed by wider detection methods (8 cases). CONCLUSIONS: There was a remarkably high rate uveitis without etiological diagnosis. The evaluation of patients with uveitis requires a careful evaluation of ocular and systemic features, followed by selected specific investigation. The indiscriminate use of diagnostic tests is not warranted.

Adolescent↗