A familial study of the inheritance of HLA-B27-positive acute anterior uveitis

To determine whether factors besides HLA-B27 play a pathogenic role in acute anterior uveitis, we examined 152 first-degree relatives of 42 randomly selected HLA-B27-positive acute anterior uveitis patients. Nine relatives, all from different families, had acute anterior uveitis: eight were HLA-B27 positive and one was HLA-B27 negative. The prevalence of acute anterior uveitis in HLA-B27-positive first-degree relatives of HLA-B27-positive acute anterior uveitis patients was 13% (eight of 63). This is significantly more (P less than .0001) than the frequency of 1% in the normal HLA-B27-positive Dutch population. Ankylosing spondylitis was found in four of 38 (11%) HLA-B27-positive family members over the age of 45 years. This is also significantly more than the prevalence of 1% in a normal HLA-B27-positive Dutch population. Of these four relatives with ankylosing spondylitis, three also had acute anterior uveitis. It was remarkable that two of these four relatives had a proband who had no ankylosing spondylitis.     

Detection of Borrelia burgdorferi DNA in urine of patients with ocular Lyme borreliosis

AIM: To evaluate the diagnostic value of the polymerase chain reaction (PCR) to detect Borrelia burgdorferi DNA in patients with ocular Lyme borreliosis. METHODS: Of 256 consecutive uveitis patients six selected individuals with clinical evidence for Lyme borreliosis and 30 patients with non-Lyme uveitis were enrolled. Lyme serology was performed by ELISA and western blotting. Urine samples were examined by an optimised nested polymerase chain reaction (PCR) protocol. RESULTS: Only four of six uveitis patients suspected for Lyme borreliosis were ELISA positive, while all six subjects showed a positive western blot. B burgdorferi PCR was positive in all of these six patients. Whereas two of the 30 controls had a positive Lyme serology, B burgdorferi DNA was not detectable by PCR in any sample from these patients. CONCLUSIONS: PCR for the detection of B burgdorferi DNA in urine of uveitis patients is a valuable tool to support the diagnosis of ocular Lyme borreliosis. Moreover, these patients often show a weak humoral immune response which may more sensitively be detected by immunoblotting.     

Clinical features of acute anterior uveitis

We studied the clinical features and prognosis of 73 patients with HLA-B27 positive and 71 patients with HLA-B27 negative acute anterior uveitis using computer analysis of more than 50 variables per patient. The patients with HLA-B27 positive acute anterior uveitis showed the following characteristics which were significantly different from patients with HLA-B27 negative acute anterior uveitis: younger age at onset; high male to female ratio; frequent unilateral alternating eye involvement; severe ocular symptoms during activity, such as presence of fibrin in the anterior chamber; absence of mutton fat keratic precipitates; high incidence of ocular complications; and frequent association with seronegative spondyloarthropathies. Despite the difference of disease severity and incidence of complications, the long-term visual outcome did not differ significantly between the two groups. No distinctions were observed when patients with HLA-B27 positive acute anterior uveitis were subdivided according to sex or the presence of ankylosing spondylitis. HLA-B27 positive acute anterior uveitis formed a distinct clinical entity associated with serious prognosis as compared to HLA-B27 negative acute anterior uveitis.     

Positive polymerase chain reaction and histology with borderline serology in Parinaud's oculoglandular syndrome

PURPOSE: To report a case of Parinaud's oculoglandular syndrome (POS) in which, despite a borderline serology, polymerase chain reaction (PCR) testing for a conjunctival biopsy was positive for Bartonella henselae, a source of cat-scratch disease. A Steiner silver stain demonstrated the organism. METHODS: Case Report. RESULTS: A 65-year-old man was seen for a foreign body in his left eye (OS) associated with chemosis and a preauricular node. CONCLUSION: B. henselae is a known cause of POS. This gram-negative pleomorphic rod has been more frequently discovered in connection with this syndrome due to improved diagnostic testing such as indirect immunofluorescence antibody and PCR testing. Frequently, serology is positive if the organism is present. This report describes a patient with clinical findings of POS who, despite borderline serology, had pleomorphic rods on Steiner silver stain and positive PCR testing compatible with Bartonella henselae.     

合并成型性渗出的急性前葡萄膜炎与HLA-B27的相关性研究

目的 探讨急性渗出性前葡萄膜炎与HLA-B27的相关性。方法 对53例前房内出现成型性渗出的急性前葡萄膜炎（AAUPE）患者及61例前房内无成型性渗出的急性前葡萄膜炎（AAU）患者进行HLA-B27的检测,并结合临床表现加以分析。结果 成型性渗出的AAUPE患者的HLA-B27阳性率为100％,而无成型性渗出的AAU患者的HLA-B27阳性率仅为50.8％。二者有显著差异性（P<0.01）。两组HLA-B27阳性的病人强直性脊柱炎发生率分别为50.0％和42.9％。结论 结果进一步证实了HLA-B27与成型性渗出密切相关的论点。提示检测AAU患者HLA-B27的阳性率,发现成型性渗出裂隙灯检查似与血清法检测同样准确。     

Acute anterior uveitis and conjunctivitis following yersinia infection in children

We studied characteristics of ocular inflammation associated with yersinia infection in six children, three boys and three girls, ranging in age between 4 and 14 years. Four patients developed acute anterior uveitis with aqueous flare and cells, small keratic precipitates, cells in the vitreous, and occasionally with fibrinous exudates, posterior synechiae and macular edema. The uveitis was unilateral in two patients and bilateral in two. In three 10- to 14-year-old patients the uveitis resolved during corticosteroid treatment in 3 to 8 (mean 6) weeks. In a 4-year-old girl with positive antinuclear antibody titers bilateral uveitis lasted for 17 weeks. Two uveitis patients had recurrent episodes. Two patients had mucopurulent bilateral mild conjunctivitis which resolved in 3 to 5 days. All patients had symptoms of reactive arthritis and one had sacroiliitis. All tested patients were HLA-B27 positive. Our results indicate that in HLA-B27 positive children, especially after the age of 10 years, yersinia infection may occasionally trigger reactive iritis or conjunctivitis which often occur together with other HLA-B27 associated rheumatic diseases.Department of Ophthalmology, University of Tampere, PO Box 607, SF-33101 Tampere, Finland     

Ophthalmic findings and frequency of extraocular manifestations in patients with HLA-B27 uveitis: a study of 175 cases

OBJECTIVE: To analyze ocular and extraocular manifestations in patients with HLA-B27-associated uveitis. DESIGN: Large, observational case series. PARTICIPANTS: One hundred seventy-five consecutive patients with HLA-B27-associated uveitis seen in a single center between January 1996 and March 2001. METHODS: Features of uveitis were noted and patients were referred systematically to rheumatologists. The history of previous uveitis attacks and extraocular manifestations of spondyloarthropathy was recorded. Assessments of spondyloarthropathies were based on criteria established by the European Spondyloarthropathy Study. MAIN OUTCOME MEASURES: Percentage of patients with extraocular manifestations. The time between the first episode of uveitis and symptoms or diagnosis of extraocular disease was estimated. Characteristics of uveitis were analyzed. RESULTS: The male-to-female ratio was 1.3 to 1, and the median age at the time of the first attack of uveitis was 31 years. An HLA-B27-associated extraocular disorder was seen in 136 cases (77.7%). Of these, ankylosing spondylitis was diagnosed in 81 patients (46.3%) and presumed in 17 (9.7%). Undifferentiated spondyloarthropathy was observed in 21 patients (12%) and other HLA-B27-associated diseases in 17 patients (9.7%). The onset of extraocular symptoms occurred at a younger age (mean+/-standard deviation [SD], 26.4+/-11.1 years) than the first attack of uveitis (mean+/-SD, 34.0+/-14.1 years; P<0.0001). The diagnosis of an extraocular disease was made only after the appearance of ophthalmic manifestations in 88 of 136 patients. Among 117 patients (66.9%) with more than 1 episode of uveitis, same eye attacks were observed in 48 of 117 patients (41.0%), more than the expected percentage than attacks of a random eye (P<0.0001). The median +/- SD frequency of active episodes of uveitis was 0.8+/-0.6 per year and decreased as the duration of the disease lengthened (P<0.0001). Patients with extraocular disease had a greater total number of attacks of uveitis (P = 0.02), but other ophthalmic findings did not differ between patients with and without an extraocular disorder. CONCLUSIONS: Uveitis is frequently the first indication of a previously undiagnosed HLA-B27-associated extraocular disease. The most common of these diseases are spondyloarthropathies.     

HLA-B27-associated acute anterior uveitis in the University Referral Centre in North Thailand: clinical presentation and visual prognosis

BACKGROUND: Acute anterior uveitis (AAU) is the most frequent type of uveitis encountered in the west. Although human leucocyte antigen (HLA)-B27-associated ankylosing spondylitis was reported in South East Asia, it is not known whether HLA-B27-associated ocular disease is prevalent in Thailand. METHODS: A prospective study of 100 unrelated blood donors and 121 consecutive patients with AAU was carried out. All people underwent HLA-B27 typing and full ocular examination. Radiological examination of the sacroiliac joints was conducted in patients with low back pain or arthralgias. RESULTS: The prevalence of HLA-B27 was 10% among the blood donors in contrast with 44% in the AAU group (p<0.001). The clinical characteristics of HLA-B27-associated AAU were similar to those published throughout the world (unilaterality in 74%, hypopyon in 31%, recurrent AAU in 64%). However, the increased intraocular pressure (IOP) was more common in the HLA-B-27-negative group (p = 0.03) than in their HLA-B27-positive counterparts. At least 15% of the HLA B27-positive group had radiological signs of ankylosing spondylitis. CONCLUSION: The prevalence of HLA-B27 in the population without uveitis in Thailand is about 10% and clinical characteristics of HLA-B27-positive AAU are similar to those reported in the west. In contrast with earlier reports, HLA-B27-negative AAU in Thailand was associated with increased IOP and should be further studied.     

Ocular bartonellosis

PURPOSE: To review recent advances in the basic and clinical biology of Bartonella-related eye disease. METHOD: A review of the pertinent medical literature was performed. RESULTS: A number of novel Bartonella species have been identified over the past decade. Of these, Bartonella henselae, the etiologic agent in cat scratch disease, is most often associated with ocular complications, which may include Parinaud oculoglandular syndrome, neuroretinitis, and focal retinochoroiditis. Although cat and flea exposure appear to be the main risk factors for contracting cat scratch disease, the diagnosis of ocular bartonellosis relies primarily on the recognition of suggestive clinical signs in conjunction with positive serologic testing. B. henselae-associated ocular complications are usually self-limited but may be treated with doxycycline or erythromycin, with or without rifampin, when the infections are severe or sight-threatening. CONCLUSIONS: B. henselae infection is common and should be considered in patients with Parinaud oculoglandular syndrome, neuroretinitis, or focal retinochoroiditis, particularly when there is a history of cat or flea exposure.     

HLA-B27-associated uveitis and cystoid macular edema

Objective: To determine which ocular and systemic characteristics are associated with cystoid macular edema (CME) in patients with HLA-B27-associated uveitis. Methods: The authors reviewed the records of 129 patients (157 eyes) with HLA-B27-associated uveitis seen at the Massachusetts Eye and Ear Infirmary from June 1980 to June 1995. Data obtained from the records included: age, gender, duration of uveitis, follow-up duration, ocular and systemic findings, presence of CME, therapeutic intervention, and visual outcome. Results: Twenty-one of 157 eyes (13.4%) with HLA-B27-associated uveitis presented with or subsequently developed CME. In 14 (67%) eyes with CME, vitreous cells were noted either at presentation or during follow-up. Forty-nine of 136 eyes (36%) without CME had vitreous cells at presentation or developed vitreous cells during follow-up. The estimated odds ratio for developing CME associated with the presence of vitreous cells was 2.9 (95% confidence interval: 1.0–8.3). No other demographic, ocular, or systemic characteristics appeared to be associated with the presence of CME. Conclusion: The presence of vitreous cells in patients with HLA-B27-associated uveitis may indicate an increased risk of CME development.     

Acute anterior uveitis and HLA-B27

Acute anterior uveitis is the most common form of uveitis. HLA-B27-associated acute anterior uveitis is a distinct clinical entity that has wide-ranging medical significance due to its ocular, systemic, immunologic, and genetic features. The association between HLA-B27 and the spectrum of HLA-B27-associated inflammatory diseases remains one of the strongest HLA-disease associations known to date. This review examines acute anterior uveitis with particular focus on HLA-B27-associated acute anterior uveitis, including the epidemiology, immunopathology, association with HLA-B27 and its subtypes, clinical features, complications, prognosis, and potential new therapies such as anti-TNFalpha therapy and oral HLA-B27-peptide tolerance. There have been substantial recent advances in both clinical and basic scientific research in this field, including studies of the various animal models of acute anterior uveitis and the HLA-B27 transgenic animals, and these are summarized in this review. To the ophthalmologist, HLA-B27-associated acute anterior uveitis is an important clinical entity that is common, afflicts relatively young patients in their most productive years, and is associated with significant ocular morbidity due to its typically recurrent attacks of inflammation and its potentially vision-threatening ocular complications. Furthermore, to the ophthalmologist and the internist, HLA-B27-associated acute anterior uveitis is also of systemic importance due to its significant association with extraocular inflammatory diseases.     

Prevalence of serologic evidence of cat scratch disease in patients with neuroretinitis

OBJECTIVE: To determine the prevalence of Bartonella henselae seropositivity in patients with a clinical diagnosis of neuroretinitis. DESIGN: Retrospective, clinic-based, cross-sectional study. PARTICIPANTS: Eighteen consecutive patients seeking treatment at the Casey Eye Institute from November 1993 through November 1998 who had neuroretinitis. METHODS: The billing and photographic records of the Casey Eye Institute were searched for patients with a primary or secondary diagnosis of neuroretinitis or Leber's idiopathic stellate neuroretinitis. Charts were then reviewed to determine the results of B. henselae antibody titers and other pertinent clinical information. MAIN OUTCOME MEASURES: Results of B. henselae serologic testing. RESULTS: Fourteen of 18 patients with neuroretinitis had serologic studies. Nine of the 14 tested patients (64.3%) were found to have elevated IgM or IgG for B. henselae, suggesting current or past infection. Patients with positive serologic analysis results tended to have worse vision at presentation. There were no other obvious differences between seropositive and seronegative groups in this study, including duration or quality of recovery. CONCLUSIONS: At our tertiary care ophthalmology institution, most tested patients with neuroretinitis had evidence of past or present cat-scratch disease based on positive serologic analysis for B. henselae, a much greater prevalence than is expected to be found in the general population or in patients with idiopathic uveitis. Further study is indicated to clarify the prevalence of cat-scratch disease in neuroretinitis and the role and efficacy of antibiotics in treatment.     

Clinical features and outcomes of HLA-b27-positive and HLA-B27-negative acute anterior uveitis in a Turkish patient population

PURPOSE: To compare the clinical features and outcomes of HLA-B27-positive and HLA-B27-negative acute anterior uveitis (AAU) in a large Turkish patient population. METHODS: Forty-four patients with HLA-B27-positive AAU and 65 with HLA-B27-negative AAU were reviewed retrospectively. HLA-B27 typing, gender, laterality, clinical features (fibrinous reaction, hypopyon formation), ocular complications, medical treatment, and final visual acuity were recorded. Statistical analyses included Student's t-test, Fisher's exact test, Yate's corrected Chi2 test, and Mann-Whitney U test. A p-value of <0.05 was considered statistically significant. RESULTS: Forty percent of all patients with AAU were found to be positive for HLA-B27 antigen. HLA-B27-positive AAU was significantly more common in males and HLA-B27-negative AAU in females. Unilateral or bilateral alternating AAU as well as fibrinous reaction and hypopyon formation were more common in HLA-B27-positive patients. Posterior iris synechiae and cataract formation were more common and systemic immunosuppressive agents were exclusively required in patients with HLA-B27-negative AAU. Visual outcome did not differ significantly between the HLA-B27-positive and HLA-B27-negative groups. CONCLUSIONS: HLA-B27 association is less common in Turkish patients with AAU than in other populations reported in the literature. Although distinct features of HLA-B27 uveitis were confirmed in our study, visual outcome did not differ from idiopathic AAU. Therefore, we believe that HLA-B27 typing in patients with AAU helps the clinician with the diagnosis. However, it has a limited value in determining the prognosis.     

Presumed ocular bartonellosis

BACKGROUND: The spectrum of diseases caused by Bartonella henselae continues to expand and ocular involvement during this infection is being diagnosed with increasing frequency. METHODS: The clinical features and visual prognosis for 13 patients with intraocular inflammatory disease and laboratory evidence of bartonellosis were investigated. There were nine patients with neuroretinitis and four with panuveitis with positive antibody titres against B henselae determined by an enzyme immunoassay (IgG exceeding 1:900 and/or IgM exceeding 1:250). RESULTS: Positive IgG levels were found for eight patients and positive IgM levels for five. Despite animal exposure of 10 patients, only two (IgG positive) cases had systemic symptoms consistent with the diagnosis of cat scratch disease. Pathological fluorescein leakage of the optic disc was observed in all affected eyes. At 6 months' follow up, 3/18 (17%) affected eyes had a visual acuity of less than 20/100, owing to optic disc atrophy and cystoid macular oedema. 12 patients (17 eyes) were treated with antibiotics; visual acuity improved two or more Snellen lines for 9/17 (53%) eyes. CONCLUSIONS: The possibility of B henselae infection should be considered in patients with neuroretinitis and panuveitis (especially in cases with associated optic nerve involvement) even in the absence of systemic symptoms typical for cat scratch disease.     

Acute anterior uveitis and HLA-B27 subtypes

The tissue antigen HLA-B27 is found in 50% of Dutch acute anterior uveitis (AAU) patients. The prevalence of HLA-B27 in the normal population is only 8%. However, only approximately 1% of HLA-B27+ individuals will develop AAU. Therefore, it is possible that the disease is associated with a particular B27 subtype. We typed lymphocytes of 36 B27+ AAU patients, of which 20 also had ankylosing spondylitis, for three serologically defined B27 subtypes (B27 W, B27 K and B27 non W/non K). These subtypes were normally associated with AAU. The subtype frequencies in the patients suffering from both AAU and AS also showed no preference for a certain subtype. Subtype-specific characteristics of the primary structure of the various B27 subtype molecules therefore cannot be responsible for the disease association.     

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.     

Risk for uveitis after laser in situ keratomileusis in patients positive for human leukocyte antigen-B27

PURPOSE: To assess the incidence of, risk for, and visual outcomes of acute anterior uveitis (AAU) in human leukocyte antigen (HLA)-B27 positive patients who had laser in situ keratomileusis (LASIK). SETTING: University-based center. METHODS: This study comprised 46 eyes of 23 HLA-B27 positive patients with a 5-year follow-up. Data on episodes of uveitis were reviewed retrospectively and the incidence rates calculated for LASIK and non-LASIK eyes. Kaplan-Meier survival probabilities were calculated for uveitis occurring during the final 36 to 60 months of the study. Survival probabilities between LASIK and non-LASIK eyes were compared. RESULTS: Twenty eyes (10 patients) had LASIK a mean of 36 months+/-2 (SD) after the diagnosis of HLA-B27. In the HLA-B27 positive patients, the incidence rates of uveitis between eyes that had and eyes that did not have LASIK were not significantly different. The incidence rates of uveitis after LASIK did not differ significantly between eyes with and eyes without episodes of uveitis before LASIK (P=.135). The probability of an eye having no episode of uveitis in the fourth and fifth year of follow-up was not significantly different between eyes that had LASIK and those that did not (P=.668). CONCLUSIONS: The occurrence rate of post-LASIK AAU in the HLA-B27 positive population was not higher than the general incidence in a similar HLA-B27 population without previous LASIK. A previous episode of uveitis did not appear to increase the risk for uveitis after LASIK in HLA-B27 positive patients.     

人类白细胞抗原与急性前葡萄膜炎的相关性

目的:探讨急性前葡萄膜炎(acute anterior uveitis,AAU)与人类白细胞抗原(human leucolyte antigen,HLA-B27)的相关性。方法:应用聚合酶链反应(sequence special prime polymer-ase chain reaction,SSP-PCR)基因检测技术,对AAU患者进行HLA-B27基因检测,观察HLA-B27阳性与阴性AAU临床特征并加以分析。结果:在36例AAU患者中,HLA-B27抗原阳性29例,阳性率81%,37例健康对照组,阳性9例,阳性率24%,两者有显著性差异(χ2=23.12,P<0.01)。结论:HLA-B27与AAU明显相关,HLA-B27阳性与阴性患者有一定程度的差异,常伴有全身脊柱关节病,采用SSP-PCR基因检测技术测定HLA-B27快速、简单、准确性高、客观性强,值得推广应用。     

Ocular manifestations of cat-scratch disease.

Bartonella henselae has only recently been isolated, characterized, and found to be the principal cause of cat-scratch disease (CSD). The availability of specific serologic investigations has allowed the recognition of a spectrum of ocular CSD syndromes that previously were ill defined and considered idiopathic. The primary inoculation complex causing regional lymphadenopathy is represented in the eye by Parinaud's oculoglandular syndrome; B. henselae is the most common cause. Leber's neuroretinitis has been identified for 80 years, and new data suggest that it is commonly a manifestation of CSD; the extent of the association remains to be determined. CSD optic neuritis is also described. The vitreoretinal manifestations include anterior uveitis, vitritis, pars planitis, focal retinal vasculitis, a characteristic retinal white spot syndrome, Bartonella retinitis, branch retinal arteriolar or venular occlusions, focal choroiditis, serous retinal detachments, and peripapillary angiomatous lesions. The pattern of ocular disease in AIDS-associated B. henselae infections is poorly delineated; unusual manifestations include conjunctival and retinal bacillary angiomatosis. The benefit of antimicrobial therapy for CSD in immunocompetent individuals has been difficult to establish, partly because most infections are self limited. Empirically, azithromycin, ciprofloxacin, rifampin, parenteral gentamicin, or trimethoprim-sulfamethoxazole provide the best therapeutic choices to minimize damage to the eye.     

HLA-B27-associated uveitis: overview and current perspectives

PURPOSE OF REVIEW: To review current knowledge about the pathogenesis, clinical presentation, and treatment of HLA-B27-associated uveitis, which is the most commonly identified cause of uveitis in community-based practice and an important cause of ocular morbidity. RECENT FINDINGS: Significant advances have been made in understanding the pathogenesis of HLA-B27-associated ocular and systemic disease, especially with regard to the genetic underpinning of these diseases. Increasing attention has also been focused on the use of alternative therapies in the treatment of HLA-B27-associated uveitis, with special attention to sulfa class antibiotics, historically have been used to treat the articular manifestations of the spondyloarthritides, and newer drugs that inhibit tumor necrosis factor-alpha. SUMMARY: The next several years promise to yield exciting new advances in understanding of the genetic epidemiology and treatment of HLA-B27-associated uveitis.