Investigating The Role Of Infectious Pathogens In Ocular

已知包括细菌、分枝杆菌、真菌、病毒和原生动物在内的感染性病原体可引起多种可识别的眼部感染，这些感染可在临床上诊断并用特异性抗生素治疗。典型的感染性眼部疾病的特征在于炎症反应，以清除宿主的侵入性微生物。有几种眼部疾病，包括肿瘤性、退行性和自身免疫性疾病，其中常规临床研究没有发现致病性感染病原体的直接证据。我们的研究小组有兴趣研究感染性病原体在眼部疾病发病机制中的作用，这可能会导致更好的诊断方法和治疗策略。在正在进行的临床研究中，我们的小组继续研究我们去年报道的人类T细胞嗜酸性病毒1型（HTLV-1）角膜病变的病因。在所有HTLV-1角膜病变的指数病例中均发现血清免疫球蛋白水平升高。对HTLV-1相关性脊髓病/热带痉挛性下肢轻瘫和成人T细胞白血病/淋巴瘤（ATL）患者队列的检查显示，血清免疫球蛋白水平升高与HTLV-1角膜病变相关，并且HTLV-1角膜病变更可能发生在ATL患者中。在一个死后地球仪的临床病理学研究中，我们证明了ATL可以在眼睛中表现为坏死性血管炎。此外，在ATL患者的结膜活检中，我们发现结膜驻留细胞表达T细胞趋化因子可能有助于浸润性淋巴瘤细胞的侵袭模式。一名患有慢性肉芽肿性疾病（CGD）并有复发性细菌感染病史的儿科患者出现脉络膜视网膜肿块，疑似脉络膜肉芽肿、眼内脓肿或眼内肿瘤。然而，对脉络膜视网膜活检标本的研究显示，平滑肌细胞和纤维组织异常增殖，伴慢性炎症，无感染性微生物的证据。这一发现扩大了CGD的眼科表现谱。最后，今年我们继续利用聚合酶链反应技术结合显微切割的力量来诊断一例培养阴性的痤疮丙酸杆菌眼内炎。该病例进一步证明了该技术在诊断由传染性病原体引起的眼部疾病和通过适当治疗预防眼部发病方面的实用性。

Infectious pathogens including bacteria, mycobacteria, fungi, viruses and protozoa are known to cause a wide variety of recognizable ocular infections that can be diagnosed clinically and treated with specific antibiotic therapy. Typically infectious ocular diseases are characterized by an inflammatory response to rid the host of the offending microorganism. There are several ocular conditions including neoplastic, degenerative and autoimmune diseases in which routine clinical investigations reveal no direct evidence of a causative infectious pathogen. Our group is interested in investigating the role of infectious pathogens in the pathogenesis of ocular diseases that may lead to better diagnostic methods and treatment strategies. In ongoing clinical studies our group continues to investigate the etiology of Human T cell Lymphotrophic Virus, Type 1 (HTLV-1) keratopathy which we reported last year. Elevated serum immunoglobulin levels were found in all of the index cases of HTLV-1 keratopathy. Examination of cohort of patients with HTLV-1 associated myelopathy/tropical spastic paraparesis and adult T-cell leukemia/lymphoma (ATL) showed that elevated serum immunoglobulin levels were associated with HTLV-1 keratopathy and that HTLV-1 keratopathy was more likely in patients with ATL. In a clinicopathologic study of a postmortem globe we demonstrated that ATL can present in the eye as a necrotizing vasculitis. Additionally, in conjunctival biopsies of patients with ATL we found that expression of T cell chemokines by conjunctival resident cells may contribute to the pattern of invasion of the infiltrating lymphoma cells. A pediatric patient with chronic granulomatous disease (CGD) and a history of recurrent bacterial infections presented with a chorioretinal mass suspicious for a choroidal granuloma, intraocular abscess or an intraocular neoplasm. The study of a chorioretinal biopsy specimen, however, revealed an unusual proliferation of smooth muscle cells and fibrous tissue with chronic inflammation without evidence of infectious organisms. This finding expands the spectrum of the ophthalmic manifestations of CGD. Finally, this year we continued to exploit the power of the polymerase chain reaction technique combined with microdissection to diagnose a case of culture negative Propionibacterium Acnes endophthalmitis. This case further demonstrates the utility of this technology to diagnose ocular disease induced by infectious agents and with appropriate treatment prevent ocular morbidity.