Investigating The Role Of Infectious Pathogens In Ocular

众所周知，包括细菌、分枝杆菌、真菌、病毒和原虫在内的感染性病原体可引起各种可识别的眼部感染，这些感染可以在临床上诊断并使用特定的抗生素治疗。典型的感染性眼病以炎性反应为特征，以清除宿主中的有害微生物。有几种眼部疾病，包括肿瘤性、退行性和自身免疫性疾病，常规临床检查显示没有直接证据表明是致病的感染性病原体。我们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，我们小组继续调查我们去年报告的人类T细胞淋巴营养病毒1型(HTLV-1)角膜病变的病原学。所有HTLV-1角膜病变的指征病例均发现血清免疫球蛋白水平升高。对HTLV-1相关性脊髓病/热带痉挛截瘫和成人T细胞白血病/淋巴瘤(ATL)患者的队列检查显示，血清免疫球蛋白水平升高与HTLV-1角膜病变有关，且ATL患者更有可能发生HTLV-1角膜病变。在尸检眼球的临床病理研究中，我们证明了ATL可以作为坏死性脉管炎出现在眼睛中。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。一位患有慢性肉芽肿性疾病(CGD)并有反复细菌感染病史的儿童患者，临床表现为脉络膜视网膜肿块，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，有慢性炎症的平滑肌细胞和纤维组织异常增殖，但没有感染生物体的证据。这一发现扩大了CGD眼部表现的范围。最后，今年我们继续利用聚合酶链式反应技术结合显微解剖的力量来诊断一例培养阴性痤疮丙酸杆菌眼内炎。这一案例进一步证明了这项技术在诊断感染性眼病和通过适当的治疗预防眼部疾病方面的应用。

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.