HLA-B27相关的前葡萄膜炎眼后节并发症的临床特点

目的探讨HLA—B27阳性的前葡萄膜炎眼后节并发症的临床特点及治疗。方法2002年1月至2005年10月就诊的前葡萄膜炎患者采用流式细胞术进行外周HLA-B27的检测，筛选出71-例82眼HLA-B27阳性前葡萄膜炎患者，分为两组：实验组为眼后节受累的患者24例31眼，对照组为眼后节未受累的患者47例51眼。另有HLA—B27阴性前葡萄膜炎患者74例116眼作参考。所有患者均进行裂隙灯、眼底镜等常规眼科查体，部分行眼底荧光血管造影。分析了HLA—B27相关的前葡萄膜炎眼后节并发症的临床特点。采用x^2检验及t检验进行统计学分析。结果71例82眼HLA—B27阳性前葡萄膜炎中有24例31眼占37．8％出现眼后节并发症者，包括：黄斑囊样水肿12例15眼占48．4％，视乳头水肿7例8眼占25．8％，而玻璃体炎最多见为21例27眼占87．1％，8例10眼占32．3％患者存在两种或两种以上的眼后节表现。74例116眼HLA—B27阴性者有8例12眼占10．3％有眼后节表现。实验组中发生前房成型纤维素渗出31眼中18眼占58．06％和积脓31眼中9眼占29．03％明显高于对照组（前房纤维素渗出51眼中3眼，5．88％，X^2=27．56，P〈0．01；前房积脓51眼中1眼，1．96％，X^2=13．20，P〈0．01）；实验组中伴发相关全身性疾病24例中有16例占66．67％的几率高于对照组（47例中有17例，31．66％，X^2=5．94，P〈0．05）。出现眼后节并发症的患者经全身及局部应用糖皮质激素治疗，31眼中有11眼最佳矫正视力≥1．0。结论HLA-B27阳性前葡萄膜炎易出现眼后节并发症，HLA—B27相关的前葡萄膜炎眼后节受累的患者发生相关全身性疾病和前房纤维素渗出与积脓的几率较高。     

Melanocyte lysis by cytotoxic T lymphocytes recognizing the MART-1 melanoma antigen in HLA-A2 patients with Vogt Koyanagi Harada disease

The MART-1/Melan-A melanoma antigen recognized by the majorityof HLA-A2-restricted tumorinfiltrating lymphocytes is a selfantigen expressed on melanocytes and the retina. We have investigatedwhether Vogt–Koyanagi–Harada (VKH) disease and sympatheticophthalmia (SO), systemic inflammatory disorders affecting variousorgans containing melanocytes, are autoimmune diseases directedtoward the MART-1 antigen. In two of three patients with VKHdisease and one patient with SO, CD8⁺ T cell clones (TCC) fromintraocular fluid of HLA-A2⁺ patients lysed T2 cells when pulsedwith a HLA-A2-binding MART-1 peptide, but not a HLA-A2-bindingpMel-17 or tyrosinase peptide, in a HLA-A2-restricted manner.These CD8⁺ TCC lysed both melanocytes and melanoma cells ina HLA-A2-restricted manner. In addition, CD8⁺ TCC recognizinga HLA-A2-binding MART-1 peptide were also established from peripheralblood mononuclear cells of a patient with VKH disease. In contrast,either CD4⁺ TCC from these patients or CD8⁺ TCC from the intraocularfluid of HLA-A2⁺ patients with uveitis associated with Behcet'sdisease or HTLV-I uveitis did not show this cytotoxicity. Theresults demonstrate that the MART-1 peptide-specific cytotoxicT lymphocytes lyse melanocytes in the eye of patients with VKHdisease or SO, suggesting that these diseases are autoimmunediseases directed toward the MART-1 antigen in HLA-A2⁺ patients.     

Apoptosis of CD4+ T cells occurs in experimental autoimmune anterior uveitis (EAAU)

To investigate the spontaneous turning off mechanism of endogenous uveitis, EAAU was induced in Lewis rats. Immunohistochemical and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) stains revealed that CD4+ T cells were predominant in the uveal tissue of EAAU and that the apoptosis of these cells had occurred and progressed throughout the inflammatory period in EAAU eyes. The immunohistochemistry and in situ hybridization for Fas ligand (FasL) expression showed that the expression of Fas ligand was increased in the EAAU eyes compared with control eyes. These results suggest that the apoptosis of CD4+ T cells may play a key role in the spontaneous turning off mechanism of intra-ocular inflammation and that the induction of apoptosis may be mediated by the Fas-FasL system in EAAU.     

HLA antigens in uveitis

HLA antigens are associated with a number of inflammatory eye diseases, most notably HLA B2 with anterior uveitis (AU). This association varies between different populations and ethnic groups. The aim of this study was to investigate the relationship between uveitis and HLA A, B and DR locus antigens in an Australian population. Seventy-two consecutive patients with uveitis were studied (37 males and 35 females) over a 6 month period. Thirty-two percent of the AU patients were HLA B27+, as were 42% of males (19% females) with their first attack of AU compared with 60% of males (23% females) with recurrent AU. The only significant difference in etiology between males and females was the greatly increased incidence of rheumatic diseases in males, in whom 77% (10/13) had radiological evidence of sacroiliitis. Additional findings included a lack of association between the HLA B7 cross reactive group and DR locus antigens in AU as well as the lack of any HLA associations in the 13 patients with posterior uveitis (PU).     

The distribution of clinical findings in Bechterew's syndrome (ankylosing spondylitis) suggests distinct genetic subgroups

One hundred and twenty-two consecutive patients hospitalized for ankylosing spondylitis (AS) were reexamined. The frequency of clinical signs and results of tests for associations are presented. Psoriasis was associated with a distal pattern of peripheral arthropathy. Spinal rigidity was predominantly seen in males. Males with phalangeal arthropathy exhibited preserved spinal mobility. This was the case also when HLA B27 positives and patients who did not have psoriasis were considered separately. HLA B27 positive patients in this group had frequently experienced acute anterior uveitis. It seems possible that the disease in such males is the result of combined predisposition to ankylosing spondylitis and psoriatic arthropathy. Hip arthropathy was frequently present in males with spinal rigidity. The associations observed confirm that AS is a heterogenous group of diseases. The term "syndrome" may be suitable for such a heterogenous group, and we prefer the term "Bechterew's syndrome" as the name of this group. When these new findings are added to the previous observations that acute anterior uveitis probably is a clinical, sex-influenced characteristic of HLA B27 positive Bechterew's syndrome, that HLA B27 negative patients with Bechterew's syndrome frequently had psoriasis and were HLA B13 and B17 negative, and that psoriasis was frequent in HLA B27 positive patients as well, we tentatively conclude that different and interacting genetic mechanisms may be involved in the etiology of Bechterew's syndrome.     

HLA antigens, psoriasis and acute anterior uveitis in Bechterew's syndrome (ankylosing spondylitis)

One hundred and twenty-two consecutively hospitalized patients with ankylosing spondylitis (AS) were reexamined. Ninety-two per cent were HLA B27 positive. Of the HLA B27 negative patients, 60% were found to have psoriasis, as opposed to 11 % of the HLA B27 positive patients. Acute anterior uveitis (AAU) was found only in HLA B27 positive patients, and more frequently in males than in females. The genetic and clinical heterogeneity of AS, together with the overlapping clinical criteria for AS and psoriatic spondylitis, may make the term "Bechterew's syndrome" preferable. Based on these findings and previous reports, we conclude that (i) AAU is a manifestation of Bechterew's syndrome in HLA B27 positive patients, (ii) HLA B27 negative patients without any obvious accompanying manifestations may suffer from psoriatic spondylitis, and (iii) genetic predisposition to psoriasis in persons who are HLA B13, B17 and B37 negative, may interact with the genetic predisposition to Bechterew's syndrome in HLA B27 positive persons and produce Bechterew's syndrome with psoriasis or psoriasis-like skin eruptions.     

Intracellular T lymphocyte cytokine profiles in the aqueous humour of patients with uveitis and correlation with clinical phenotype

This study aimed to investigate whether T cells in aqueous humour are different in different types of uveitis and correlate with clinical phenotype. Patients with clinically different types of uveitis, but all displaying active anterior uveitis, were phenotyped and samples of aqueous humour (AH) and peripheral blood (PB) collected. Cells from AH and PB were separated by centrifugation and by density gradient centrifugation (to obtain mononuclear cells PBMC), respectively. Cells were activated with PMA and ionomycin in the presence of Brefeldin A, stained for surface markers and intracellular cytokines, and analysed by flow cytometry. The cytokine profile was correlated with the clinical phenotype. Increased percentages of interleukin (IL)-10+-, but not interferon (IFN)-gamma+ T lymphocytes were found in AH compared with PB in patients with acute anterior uveitis (AAU), FHC or chronic panuveitis (PU). There was a trend towards elevated levels of IL-10+ T cells in AH from patients with FHC compared with AH from acute uveitis and panuveitis patients. Increased levels of IL-10+ T cells in AH compared with PB were also found in samples from patients with isolated uveitis, but not those with associated systemic disease. Levels of cytokine-positive T cells were not associated with the use of topical steroids or to the severity of the anterior uveitis. While type I cytokine-producing T lymphocytes are present in AH during AU, the presence of increased proportions of IL-10+ T lymphocytes in AH from patients with uveitis may be indicative of an anti-inflammatory mechanism that may influence the type and course of ocular inflammation in these patients.     

Ocular autoimmunity: the price of privilege?

Summary:  The eye is the prototypic immune-privileged organ. Its antigens were once believed to be expressed exclusively in the eye, which resides behind an efficient blood–organ barrier, and were believed to be unknown to the immune system. Self-tolerance to ocular components was therefore believed to be based not on immune tolerance but on immune ignorance. It is now known that the relationship between the immune system and the eye is much more complex. On the one hand, immune privilege is now known to involve not only sequestration but also active mechanisms that (i) inhibit innate and adaptive immune processes within the eye and (ii) shape the response that develops systemically to antigens released from the eye. On the other hand, retinal antigens are found in the thymus and have been shown to shape the eye-specific T-cell repertoire. However, thymic elimination of self-reactive T cells is incomplete, and such 'escapee' T cells are tolerized in the periphery as they recirculate through the body by encounter with self-antigen in healthy tissues. Due to the relative inaccessibility of the healthy eye to the immune system, peripheral tolerance mechanisms may not operate efficiently for ocular antigens, leaving a weak link in the homeostasis of tolerance. The case shall be made that although immune privilege protects vision by keeping the immune system at bay, a potential for developing destructive anti-retinal autoimmunity may be the price for the day-to-day protection afforded by immune privilege against inflammatory insults.     

Suprachoroidal Injection of Triamcinolone Acetonide Injectable Suspension for the Treatment of Macular Edema Associated With Uveitis in the United States: A Cost-Effectiveness Analysis

ObjectivesSuprachoroidal injection of triamcinolone acetonide is the first Food and Drug Administration–approved treatment for macular edema associated with uveitis. A cost-effectiveness analysis was performed comparing this treatment with best supportive care (BSC) for the management of this indication from US Medicare and commercial payer perspectives.MethodsA patient-level simulation was developed per the patient characteristics and changes in best-corrected visual acuity letter scores observed in a phase III study of triamcinolone acetonide (PEACHTREE). The wholesale acquisition cost of triamcinolone acetonide was $1650/injection; suprachoroidal injection cost was assumed at $200/injection. Healthcare costs were informed by a US claims–based analysis. Mortality risk associated with severe vision loss and blindness was modeled by applying a hazard ratio to all-cause mortality rates of the US general population. Health-related quality of life weights, obtained from a regression model fitted to the Visual Function Questionnaire-25 data from PEACHTREE, were applied based on the best-corrected visual acuity scores of both eyes. Costs (2020 US dollar) and benefits were discounted at 3% annually. Incremental cost-effectiveness ratios were estimated over a 10-year horizon.ResultsIn the base-case, the incremental cost-effectiveness ratio comparing triamcinolone acetonide with BSC was $28 479 per quality-adjusted life-year gained. The wholesale acquisition cost for triamcinolone acetonide for suprachoroidal use was ～68%, ～56%, and ～27% below the willingness-to-pay thresholds of $150 000, $100 000, and $50 000 per quality-adjusted life-year gained, respectively. Results were robust in sensitivity and scenario analyses.ConclusionsTriamcinolone acetonide for suprachoroidal use is cost-effective compared with BSC for patients with macular edema associated with uveitis.     

超声乳化术治疗色素膜炎并发性白内障

目的 评估色素膜炎并发性白内障超声乳化手术的疗效。方法 钝化分离瞳孔后粘连及剪除机化膜,牵拉扩张瞳孔后,采用原位碎核技术对19例（21只眼）色素膜炎并发性白内障行超声乳化,结果 术后1周矫正视力≥0.5者16只眼（76.2%）,≥0.2者18只眼（85.7%);手术并发症为虹膜损伤,角膜水肿,未见后囊膜破裂及角膜失代偿;术后19只眼（90.5%)恢复圆瞳孔;2只眼（9.5%)瞳孔不规则。结论 超声乳化术治疗色素膜炎并发性白内障,具有对虹膜损伤小,术后前房炎症反应轻,视力早期恢复等优点,值得推广应用。