 |
|
|
|
|
HIV患者的眼科并发症
Lucia Sobrin, M.D., Janet L. Davis, M.D.
译者：吴婵 博士 北京协和医院 眼科 Email：wuchan99@gmail.com
审阅者：张峣 博士 北京协和医院 感染科 Email：zhangyao1@gmail.com
叶俊杰 教授 北京协和医院 眼科
INTRODUCTION Immunosuppression related to HIV infection is associated with a wide variety of ophthalmic diseases, some of which are potentially blinding. The introduction of HAART has altered the incidence, prevalence and natural history of ocular opportunistic infections. The primary clinician needs to assess ocular signs and symptoms and, if appropriate, refer patients for ophthalmologic evaluation. This chapter will describe the presentation, diagnosis and treatment of the most common ophthalmic diseases seen in HIV. It is organized by ocular anatomic location. 简介 HIV相关的免疫抑制会导致多种眼科疾病，有些可以致盲。高效抗逆转录病毒治疗（Highly active antiretroviral therapy，HAART）的出现改善了眼部机会性感染的发病率，患病率及其自然病程。首诊医师需要评估眼部症状及体征，如有必要，请眼科医生对患者进行专科评估。本章按眼部解剖部位描述了HIV常见眼科疾病的表现，诊断及治疗。
EPIDEMIOLOGY In the early 1980s, case series showed the prevalence of ophthalmic lesions in patients with AIDS to be between 40 and 73% (34, 70, 20). The most common findings were HIV retinopathy (cotton wool spots, microaneurysms, retinal hemorrhages) and cytomegalovirus (CMV) retinitis. With the introduction of HAART, the incidence of CMV retinitis declined markedly from 21.9 per 100-person years in 1994 to 3.7 per 100 person-years in 1997 (63). 流行病学 20世纪80年代初，一系列病例表明AIDS患者眼部病变的患病率为40-73% (34, 70, 20)。最常见的是HIV性视网膜病（棉絮斑，微血管瘤，视网膜出血）及巨细胞病毒性（CMV）视网膜炎。随着HAART的出现，CMV性视网膜炎的发病率显著降低，从1994年的21.9每100人每年降至1997年的3.7每100人每年(63)。
DIFFERENTIAL DIAGNOSIS 分类诊断 Subjective Complaints 主诉 Blurred Vision
视力模糊 a. 屈光不正 b. 老花眼 c. 视网膜或视神经病变
飞蚊征 a. 退行性变的漂浮物 b. 眼部病变所致炎性浮游体 Eye Pain
眼痛 c. 眼表感染 d. 干眼症 e. 眼眶病变 Double Vision
复视 a. 颅神经麻痹 b. 眼眶病变 c. 斜视（眼轴未对位） Visual Field Defects
视野缺损 a. 视网膜病变 b. 视神经病变 c. 中枢神经系统病变 Visible Lesions of the Adnexae and External Eye 可见的眼附属器及外眼病变
Inflammation of Anterior Segment (Iritis) 前节炎症（虹膜）
Retina and Choroid 视网膜和脉络膜
Neuro-ophthalmic 神经眼科
Orbital 眼眶
RISK FACTORS HIV retinopathy is associated with increased HIV viral load and decreasing CD4+ T lymphocyte counts. Opportunistic ocular infections and neoplasms typically occur late in the course of HIV infection. The CD4+ T lymphocyte count is more predictive of risk than the HIV viral load. CMV retinitis typically occurs with a CD4+ T lymphocyte count less than 100. Repeated or active herpetic infections (simplex or zoster) increase the risk of necrotizing herpetic retinitis as does ipsilateral herpes zoster ophthalmicus or disseminated cutaneous herpes. The risk of toxoplasmic chorioretinitis when cerebral toxoplasmosis is present has not been quantified. One study reported finding ocular toxoplasmosis in 18% of a small group of patients with a recent diagnosis of toxoplasmic encephalitis (1). Bacterial or fungal corneal ulcers are more common in contact lens wearers. Candidal and aspergillus endophthalmitis are associated with disseminated fungal infection and intravenous drug use. Chronic fungal sinusitis increases the risk of orbital aspergillosis. Pneumocystic choroiditis was associated with inhalational prophylaxis for pneumocystis pneumonia and is rarely if ever seen if systemic oral medications are used for prophylaxis. Diabetic retinopathy ordinarily does not occur until after at least 5 years of diabetes. It is unknown whether patients taking HAART who develop diabetes will develop retinopathy at an accelerated rate. 危险因素 HIV视网膜病与HIV病毒载量的增加及CD4+ T淋巴细胞数量的降低相关。机会性眼部感染及肿瘤主要发生于HIV感染病程晚期。CD4+ T淋巴细胞数量比HIV病毒载量更能预测危险性。CMV性视网膜炎主要发生在CD4+ T淋巴细胞数量小于100时。反复或活动性疱疹病毒感染(单纯疱疹或带状疱疹)增加了坏死性疱疹性视网膜炎及同侧眼部带状疱疹或播散性皮肤疱疹的发生风险。脑弓形虫病时发生弓形虫性脉络膜视网膜炎的风险尚未量化。一项研究报道在18%的一小组新近诊断弓形虫脑炎的患者中发现了眼部弓形虫病(1)。 细菌性或真菌性角膜溃疡常见于隐形眼镜佩戴者。假丝酵母菌及曲霉菌性眼内炎与播散性真菌感染及静脉用药有关。慢性真菌性鼻窦炎增加了眼眶曲霉菌病的风险。肺孢子虫性脉络膜炎与吸入性预防肺孢子虫性肺炎相关，但用口服药预防时罕见。 糖尿病视网膜病通常至少在5年糖尿病后发生。应用HAART的患者患糖尿病后是否更快出现视网膜病尚不清楚。
CLINICAL MANIFESTATIONS 临床表现 Signs and Symptoms Subjective 主观的表征及症状 Complaints: Blurred vision is most commonly due to refractive error or presbyopia. AIDS patients lose accommodation prematurely; reading glasses may be required in the early 30’s. However, blurred vision may also be a sign of serious retinal or optic nerve disease. Floaters are spots in the vision that drift or float with eye movements. Translucent and linear floaters are likely to be benign, degenerative floaters, but pinpoint black specks or black strands may indicate serious retinal infection or intraocular hemorrhage. Eye pain is virtually always an important sign of ophthalmic disease, especially if associated with redness, sensitivity to light, or blurred vision. Double vision or field defects may indicate either ocular or neurologic disease and are important clinical symptoms. The mnemonic RSVP is used in patient education to ask them to report redness, sensitivity to light, visual disturbance, or pain. 主诉: 视力模糊最常由屈光不正或老花引起。AIDS患者过早丧失适应性调节能力；30多岁早期可能就需要阅读眼镜。但是，视力模糊也可能是严重视网膜或视神经病变的表征。漂浮物是视物时出现的随眼球运动漂移或飘动的斑点。半透明的线性漂浮物可能是良性的退行性变的漂浮体，但极小的黑点或黑线可能预示着严重的视网膜感染或眼内出血。实际上眼痛常为眼部病变的重要征象，尤其和眼红，畏光或视力模糊相关时。复视或视野缺损可能预示着眼部或神经病变，是重要的临床症状。应提醒患者及时报告报告眼红，畏光，视力降低或疼痛的症状。 Visible Lesions Of The External Eye Raised Eyelid Lesions: Solitary or grouped 1-3 mm papules with a slightly rough surface and a central depression are characteristic of molluscum contagiosum. Ocular irritation and a red eye may occur if the lesions are on the eyelid margin, but molluscum is otherwise painless and there is no associated hyperemia of the skin. Styes (hordeola) and chalazia arise deep within the eyelid glands and have intact or slightly flaked or crusted skin; they are larger and harder than molluscum bodies. If infected (hordeola), they will be painful and red. 可见的外眼病变引发的眼睑病变: 孤立或成簇的表面轻度粗糙，中央凹陷的1-3 mm的丘疹是感染性软疣的特征。如果病变位于睑缘，可出现眼部刺激，眼红，否则软疣是无痛的，和皮肤充血也无关。麦粒肿（睑板腺炎）及霰粒肿发生于睑板腺深处，皮肤完好，可轻微脱屑或结痂；它们比软疣疣体更大，更硬。如果感染（睑板腺炎），会疼痛，发红。 Kaposi Sarcoma Lesions: (2) are painless macules or papules of deep red to purple color; older lesions may appear brown. There is a wide size range. Distortion of the eyelid by tumor growth or hemorrhage can cause ocular irritation, trichiasis (turning in of eyelashes), periorbital edema or mechanical visual obstruction from ptosis. 卡波西肉瘤: (2) 是无痛性深红色至紫色斑疹或丘疹，陈旧病变可表现为棕色。肉瘤大小范围较广。瘤体生长或出血所致眼睑变形可致眼部刺激，倒睫（睫毛向内转），眶周水肿或机械性视物障碍--上睑下垂所致。 Herpes Zoster Ophthalmicus: presents as painful, crusted vesicles in the distribution of the ophthalmic branch of the trigeminal nerve (6). Pain, red eye, tearing, foreign body sensation, and photophobia may be seen if there is associated corneal disease or iritis. 眼部带状疱疹: 呈沿三叉神经眼支分布的痛性结痂囊泡(6)。如有相关的角膜病变或虹膜炎，可出现疼痛，眼红，流泪，异物感及畏光。 Anterior Segment: Conjunctival neoplasms in HIV positive patients are CIN (conjunctival intraepithelial neoplasia) and Kaposi sarcoma (45). The symptoms associated with CIN are most often redness and foreign body sensation. The lesion is usually pink, raised, and located at the junction of the cornea and the conjunctiva. Pterygia or pingueculae are benign actinic changes that occur in palpebral fissure and may have the same appearance and symptoms as CIN. Acute and chronic conjunctivitis may appear as a diffuse moderate redness with or without discharge. Small bumps can sometimes be seen inside the lower eyelid. 前节: HIV阳性患者的结膜新生物为CIN (结膜上皮内瘤)和卡波西肉瘤(45)。CIN最常见的相关症状为充血及异物感。病变常为位于角膜结膜移行处的粉红色突起。翼状胬肉或睑裂斑是发生在睑裂处的良性光化性改变，和CIN可有同样的外观。急慢性结膜炎可表现为弥漫性中度充血，有或无分泌物。有时可见下睑内小肿块。 Redder, more hemorrhagic appearing lesions may be simple subconjunctival hemorrhages or Kaposi sarcoma (2). Kaposi sarcoma of the conjunctiva is often asymptomatic. It is a thicker, redder lesion than subconjunctival hemorrhage. It may be multicentric. Since it typically affects the inferior conjunctiva, pulling down the lower eyelid as the patient elevates the eye may be necessary to see the lesion. 更红，出血更多的病变可能是单纯结膜下出血或卡波西肉瘤(2)。结膜卡波西肉瘤通常无症状，比结膜下出血更厚更红，可为多灶性。因其主要侵及下方结膜，需要在患者上转眼球时将下睑下拨，可见病变。 Elevated Nodules: on the conjunctival surface are always significant. Irregular fibrosis may indicate invasive squamous cell carcinoma. Lymphoma appears as a homogeneous salmon-colored patch. Scleritis, which is sometimes infectious, is red and painful. 突起的结节:位于结膜表面常意义重大。不规则纤维化可能意味着侵润性鳞状细胞癌。淋巴瘤表现为均匀的肉色斑块。巩膜炎时眼红痛，有时可传染。 Loss of the shiny, smooth appearance of the cornea indicates an epithelial defect that can be confirmed with fluorescein staining and a cobalt blue light. Epithelial defects are seen with infectious corneal ulcers from trauma, contact lens wear or conjunctivitis. They typically cause pain, tearing, red eye, foreign body sensation, discharge and blurred vision. Corneal abrasion from minor trauma may present with the same symptoms and an epithelial defect, but on inspection with a penlight, corneal infections are characterized by a white infiltrate or clouding of the cornea. Patients with HIV infection may be more prone to develop corneal infections following simple corneal abrasions. Aggressive pseudomonal keratitis has been reported in AIDS patients (60). 角膜失去光泽平滑的外表表明上皮缺损，荧光素染色后钴蓝光观察可确诊。上皮缺损可见于创伤、佩戴角膜接触镜或结膜炎所致感染性角膜溃疡。典型者可致疼痛，流泪，眼红，异物感，分泌物增多及视力模糊。小创伤所致角膜磨损可有相同症状及上皮缺损，但以笔式手电检查时，角膜感染的特征为角膜的白色侵润或云翳。HIV感染患者在单纯角膜磨损后可能更倾向于发展为角膜感染。已有AIDS患者侵袭性假单胞菌性角膜炎的报道(60)。 Herpes Zoster Keratitis: is not associated with a discharge and may occur in the absence of skin lesions in patients with HIV, although presence of a vesicular skin lesion on the ipsilateral side on the tip of the nose confers a higher probability of corneal involvement (Hutchinson’s sign) (16). Pain is the prominent symptom in herpes zoster keratitis, and a prolonged course is more common in patients with HIV (4). Herpes simplex keratitis is also more likely to have a prolonged course and frequent recurrences in HIV patients (31). Microsporidial keratitis is often bilateral and may be associated with symptoms of concomitant sinus or pulmonary disease (77). It is more common in subtropical climates. 带状疱疹性角膜炎: 无分泌物，并可发生于HIV患者无皮肤病变时，尽管同侧鼻尖的疱性皮肤病变使角膜受累(Hutchinson’s征)的概率更高(16)。疼痛是带状疱疹性角膜炎的突出症状，且HIV患者病程延长(4)。HIV患者的单纯疱疹性角膜炎也更可能出现病程延长及频繁复发(31)。微孢子虫性角膜炎常为双侧，可伴有鼻窦及肺部病变(77)。亚热带气候时更常见。 Keratitis Sicca: or dry eye syndrome, is present in 20-25% of patients with HIV infection and presents with dry eye sensation, foreign body sensation, redness, and sometimes associated with dry mouth (26). Signs of the disease, such as decreased tear lake and fluorescein staining of the cornea, are best appreciated with a slit lamp examination. 干燥性角膜炎: 或干眼症，20-25%的HIV感染患者可出现，可有眼干，异物感，眼红，有时有口干(26)。该病的体征，如泪湖减少及角膜荧光素染色，最好以裂隙灯检查评定。 Inflammation of the Anterior Segment (Iritis): The symptoms of iritis, regardless of cause, are pain, photophobia, headache, red eye, and decreased vision. Iritis is a diagnosis made at the slit lamp by observation of white blood cells floating in the anterior chamber. 前节炎症(虹膜炎): 不考虑病因，虹膜炎的症状有疼痛，畏光，头痛，眼红及视力下降。裂隙灯下观察到前房中浮游的白细胞即可诊断虹膜炎。 Iritis may be associated with one of the many ocular opportunistic infections discussed elsewhere in this chapter or with immune recovery and a heightened immune response to a previous, healed retinal CMV infection. Iritis occurs in fewer than 1 in 100 patients taking rifabutin (36, 72, 73, 84) and about 1 in 10 patients receiving cidofovir (12). Rifabutin uveitis is typically acute in onset, unilateral or bilateral, and severe (36, 84). It is occasionally so severe as to produce a hypopyon that may be seen with a penlight as a layering out of white blood cells in the anterior chamber. Cidofovir, in both its intravitreal and intravenous forms, can cause iritis (3,12). Onset is typically 4 or 5 days after a dose of drug and may have mild symptoms although continued dosing may increase the intensity. Low eye pressure caused by cidofovir may result in permanently reduced vision. 虹膜炎可能和本章讨论的多种眼部机会性感染之一有关，或与先前已治愈的视网膜CMV感染后免疫复原及高免疫反应有关。服用利福布汀的患者的虹膜炎发生率小于1/100(36, 72, 73, 84)，接受西多福韦治疗的患者约1/10(12)。典型利福布汀性虹膜炎急性发作，单侧或双侧，且病情严重(36, 84)。有时重至产生前房积脓，笔式手电可见前房中成层的白细胞。玻璃体腔内及静脉内应用西多福韦都可致虹膜炎(3,12)。典型的发作是在用药后4或5天，症状可以很轻，尽管持续用药可加重。西多福韦所致低眼压可致永久性视力减退。 Iritis due to reactive arthritis (Reiter syndrome) or other HLA-B27 associated diseases may continue even after the onset of immunosuppression from HIV infection. The attacks of iritis are characteristically unilateral, severe, and of sudden onset. 反应性关节炎（Reiter综合征）或其他HLA-B27相关疾病所致虹膜炎甚至在HIV感染导致免疫抑制后仍可持续。其虹膜炎发作特点为单侧，严重，且突然发作。 Retina and Choroid: Posterior segment disease can be divided into three categories: vascular, infectious, and neoplastic. 视网膜及脉络膜: 后节病变可分为三种：血管性，感染性及新生物性。 Vasculopathy: HIV retinopathy is the most frequent form of ocular involvement seen in patients with AIDS and is most often asymptomatic. The most common findings are retinal cotton wool spots in the posterior pole; retinal hemorrhages and microaneurysms similar to diabetic retinopathy can also be seen. Cotton wool patches are the same yellow-white color as retinal infections, but are less than one-half disc diameter in size, have a feathered edge, and fade within 6 to 8 weeks. HIV retinopathy does not affect vision unless there is severe capillary closure. A presumed variant of HIV retinopathy may rarely lead to closure of large arterioles or venules in the eye with sudden loss of vision. 血管病: HIV性视网膜病是AIDS患者眼部受累的最常见形式，且大多无症状。最常见表现为后极部视网膜棉絮斑；还可见类似糖尿病性视网膜病的视网膜出血及微血管瘤。棉絮斑为黄白色，与视网膜感染相同，但大小小于1/2视盘直径，边缘羽毛状，并于6-8周内消退。直到出现严重的毛细血管闭塞，HIV性视网膜病才会影响视力。一种尚未确定的变异性HIV视网膜病可偶然导致眼内大的小动脉或小静脉闭塞而致突然失明。 Diabetic Retinopathy: in HIV patients with preexisting diabetes appears to be more severe and rapidly progressive, presumably from cumulative damage to the vascular beds. 糖尿病视网膜病:先前患有糖尿病的HIV患者似乎更严重并迅速进展，大概源自血管床的双重损伤。 Infectious Retinitis and Choroiditis: The most frequent symptoms of infectious retinitis are decreased vision, visual field defect, and floaters. Pain and redness are rare in viral retinitis associated with HIV infection. Infections may be totally asymptomatic if the lesions are small or peripheral. The appearance of the retina and choroid as examined by an experienced ophthalmologist is often sufficient to diagnose a specific infection based on characteristic signs. The most frequent symptoms of CMV retinitis are floaters and vague visual complaints. Up to 54% of patients with CMV retinitis may be asymptomatic at the time of diagnosis after routine screening (49). The characteristic fundus lesion is a slowly expanding, yellow-white, granular lesion with an active border and a scarred center. The lesion is often wedge-shaped or arcuate, following a vascular pattern. Satellite lesions, perivascular sheathing, intraretinal hemorrhages (“pizza fundus”), and retinal detachment may also be seen. 感染性视网膜炎及脉络膜炎: 感染性视网膜炎最常见的症状为视力下降，视野缺损及飞蚊征。HIV感染相关的病毒性视网膜炎罕见疼痛及眼红。如果病变较小或位于周边，感染可以完全无症状。有经验的眼科医师检查视网膜及脉络膜的外观通常就足以根据其特有的表征诊断特异性感染。CMV性视网膜炎的常见症状为飞蚊征及视物模糊。高达54%的CMV性视网膜炎患者在常规筛查后诊断时可无症状(49)。其特征性眼底病变为缓慢延伸的黄白色颗粒状病变，周边活动，中心为疤痕。病变常为楔形或弓形，沿血管走形。还可见卫星灶病变，血管旁鞘，视网膜内出血（“比萨样眼底”）及视网膜脱离。 In some patients with preexisting CMV retinitis, immunologic improvement with HAART therapy increases intraocular inflammation. This immune recovery uveitis appears to be a reaction to CMV antigens and can occur in patients whose lesions are either active or inactive. In one study, its onset was 2 to 16 weeks (median 4 weeks) after increase in CD4+ T lymphocyte counts (43). Another group reported a lag time of up to eight months between the addition of a protease inhibitor and the onset of inflammation (90). Floaters and painless loss of vision are frequent symptoms. Inflammatory cells in the vitreous humor and optic disc edema are the most common findings. Immune recovery uveitis can lead to chronic, vision-limiting complications, including macular edema and epiretinal membrane formation. The incidence has been widely estimated at 5 to 30% of patients with preexisting CMV retinitis who begin HAART therapy. 提高免疫的 HAART疗法可使一些先前患有CMV性视网膜炎的患者发生眼内炎症增加。这种免疫恢复性葡萄膜炎似乎是对CMV抗原的应答，病变活动或不活动的患者都可发生。一项研究报道在CD4+ T淋巴细胞计数增加后2-16周（平均4周）发作(43)。另一组报道的时间间隔更长，增加蛋白酶抑制剂和炎症发作间隔长达8个月(90)。飞蚊征及无痛性视力丧失是常见症状。玻璃体内炎性细胞及视盘水肿是最常见的发现。免疫重建性葡萄膜炎可致慢性视力受损，包括黄斑水肿及视网膜前膜形成。估计先前患有CMV性视网膜炎的患者开始HAART治疗后发病率为5-30%。 Necrotizing Herpetic Retinitis: is caused by herpes zoster or herpes simplex I and II viruses (8, 83). A unilateral or bilateral, confluent, rapidly progressive, necrotizing retinitis that starts in the periphery and spreads centripetally is typical. In HIV-infected patients, there may be a complete lack of inflammatory signs such as hyperemia, iritis or vitritis; this destructive variant has been called progressive outer retinal necrosis. In one study, bilateral blindness occurred in two-thirds of patients treated with acyclovir within one month of onset. There is also a higher risk of retinal detachment in necrotizing herpetic retinitis than in CMV retinitis. 坏死性疱疹性视网膜炎:由带状疱疹病毒或单纯疱疹病毒I型及II型引起(8, 83)。典型表现为始于周边部并向后极部蔓延的单侧或双侧，融合性，快速进展的坏死性视网膜炎。感染HIV的患者可能完全缺乏炎性体征，如充血，虹膜炎或玻璃体炎；这种破坏性病变称为进展性外部视网膜坏死。一项研究中，发作一个月内应用阿昔洛韦治疗的患者有2/3双眼失明。坏死性疱疹性视网膜炎发生视网膜脱离的危险也高于CMV性视网膜炎。 Toxoplasmic Chorioretinitis: classically presents with focal chorioretinal inflammation at the border of an existing chorioretinal scar. However, in patients with AIDS, there is often no visible chorioretinal scar and the lesions may be very large. Usually more intense inflammatory reaction with floaters and pain is noted than with viral retinitis. 弓形虫性脉络膜视网膜炎: 经典表现为原有脉络膜视网膜瘢痕边缘的局灶性脉络膜视网膜炎症。但AIDS患者通常无可见的脉络膜视网膜瘢痕，且病变可以很大。通常比病毒性视网膜炎的飞蚊征及眼痛等炎性反应更强烈。 Syphilitic Chorioretinitis: Syphilitic chorioretinitis is usually seen in the secondary stage of syphilis. HIV-infected patients may have active syphilitic uveitis without a positive RPR or VDRL and often have recurrent disease despite treatment (30). The most classic findings are yellow, deep infiltrates in the temporal macula, and vitritis. The appearance may vary widely, however, and may resemble CMV retinitis. 梅毒性脉络膜视网膜炎: 梅毒性脉络膜视网膜炎通常见于二期梅毒。感染HIV的患者可有活动性梅毒性葡萄膜炎而非RPR或VDRL阳性，即使给以治疗，也有复发(30)。最经典的表现为颞侧黄斑的黄色深层侵润及玻璃体炎。其表现变化多端，可以类似CMV性视网膜炎。 Cryptococcal Choroiditis: Cryptococcal choroiditis was more common before efficient antifungal prophylaxis. It remains common in Africa. Dissemination from non-CNS sites produces the most widespread choroidal involvement. Ocular manifestations of cryptococcal meningitis are usually confined to the optic nerve (see below), but there may be spread to the adjacent retinochoroid. 隐球菌性脉络膜炎:隐球菌性脉络膜炎在进行有效的抗真菌预防前更常见。在非洲仍很常见。最广泛的脉络膜受累由源于非中枢神经系统部位的播散产生。隐球菌性脑膜炎的眼部表现通常限于视神经（见下文），但乙脑可播散到临近视网膜脉络膜。 Pneumocystis Choroiditis: Pneumocystis choroiditis is a rare complication of advanced HIV disease, occurring most often in the context of systemic pneumocystosis (66). It has a distinct appearance of sparse, oval, deep, choroidal, homogenous, yellow to orange, multifocal, posterior lesions. Vitritis is not seen. Patients are frequently asymptomatic or have only mild visual symptoms even when lesions are directly under the fovea (48). 肺孢子虫性脉络膜炎:肺孢子虫性脉络膜炎是罕见的晚期HIV病的并发症，最常发生于系统性肺孢子虫病时(66)。其表现独特，为稀疏的多灶性深在均匀黄色至橙色卵形脉络膜后部病变。未见玻璃体炎。患者常无症状或仅有轻度视觉症状，即使病变正位于中心凹下(48)。 Endogenous Endophthalmitis: Endogenous endophthalmitis can occur in virtually any disseminated bacterial or fungal disease. Certain organisms predominate. In candidal endophthalmitis, choroidal infiltrates enlarge to form a white nodule that penetrates the retina and seeds the vitreous cavity (“fungus ball”). A thick, diffuse, yellow chorioretinal plaque that typically involves the macula and vitritis is typical of aspergillus endophthalmitis. Histoplasmosis capsulatum can cause bilateral chorioretinitis characterized by large subretinal nodules and secondary retinal detachment (28). Sepsis with any bacterial organism may lead to a focal retinochoroiditis with inflammation or to a panophthalmitis with loss of the eye. Disseminated tuberculosis rarely involves the eye. It is characterized by elevated, focal, white, outer retinal lesions that are slowly progressive and relatively well tolerated for prolonged periods (64). Bartonella henselae (cat scratch disease) is a less serious systemic infection that may involve the eye with multiple, small retinal infiltrates and vascular occlusions. These infiltrates may be confused with the cotton wool spots of HIV retinopathy (37). 内源性眼内炎:内源性眼内炎事实上可发生于任何播散性细菌或真菌疾病。某些菌群占优势。假丝酵母菌性眼内炎时，脉络膜侵润扩大，形成白色结节，穿透视网膜并播散至玻璃体腔（“真菌球”）。通常涉及黄斑及玻璃体的弥漫性黄色脉络膜视网膜厚斑块是曲霉菌性眼内炎的典型特征。荚膜组织胞浆菌病可致双侧脉络膜视网膜炎，特征为视网膜下大结节及继发性视网膜脱离(28)。任何细菌病原体所致脓毒症可致局灶性视网膜脉络膜炎，出现炎症反应，甚至发展为全眼球炎，损害整个眼球。播散性肺结核很少涉及眼部。其特点为突起的局灶性白色外部视网膜病变，进展缓慢，可长期较好忍受(64)。巴尔通体（猫抓病）是一种病情较轻的系统性感染，可累及眼部，表现为多发的视网膜小侵润及血管闭塞。这些侵润可与HIV性视网膜病的棉絮斑混淆(37)。 Neoplasms: Intraocular tumors are rare in HIV. Non-Hodgkin's B-cell lymphoma is the most common type of intraocular lymphoma. Despite the relative frequency of NHL in AIDS, intraocular lymphoma is rare. Melanoma is the most common intraocular tumor of adults, but no increase in incidence in AIDS has been reported. Choroidal metastases are most likely to occur from breast, lung, gastrointestinal and prostate malignancies. 肿瘤:HIV罕见眼内肿瘤。非霍奇金氏B细胞淋巴瘤是最常见的眼内淋巴瘤类型。尽管NHL在AIDS相对多见，但眼内淋巴瘤很少发生。黑色素瘤是成人最常见的眼内肿瘤，但其在AIDS中的发病率增加未见报道。脉络膜转移癌最可能源于乳房，肺，胃肠道及前列腺的恶性肿瘤。 Neuro-Ophthalmic: Infections may directly affect the optic nerve with profound loss of vision. The most common cause of neuroophthalmic lesions in patients with HIV is cryptococcal meningitis (46). Vision loss and/or visual field defects can result from meningitis-related papilledema or optic neuropathy from direct infiltration of the optic nerve by fungi anywhere along its path. An afferent pupillary defect may be seen in these cases. Sudden, profound vision loss from optic nerve cryptococcosis has been reported but is rare (5). Cryptococcus can also produce cranial nerve palsies, particularly cranial nerve VI palsies, with double vision and abduction defects of the ocular movements. 神经眼科:感染可以直接侵袭视神经，视力严重丧失。HIV患者神经性眼病最常见的病因为隐球菌性脑膜炎(46)。脑膜炎相关性视乳头水肿或因真菌直接侵润视神经通路上任何位置所致视神经病可导致视力丧失和/或视野缺损。传入性瞳孔阻滞可见于这些病例。视神经隐球菌病引起突然性重度视力丧失已有报道，但很罕见(5)。隐球菌还可引起颅神经麻痹，尤其是第VI颅神经麻痹，出现复视及眼球外展运动不足。 Toxoplasmic papillitis: Toxoplasmic papillitis has been reported as an initial manifestation of AIDS and presents with vision loss and optic nerve edema. Associated chorioretinitis may be present (18). Herpes class virus (varicella, simplex, or CMV) can infect the papilla directly. In the case of herpes zoster or simplex, a retrobulbar neuritis with sudden vision loss may precede the typical fundus findings of necrotizing herpetic retinitis by a few days. Ethambutol may cause an optic neuropathy characterized by reduced color vision and optic nerve pallor. An optic neuritis has been associated with didanosine therapy (50). 弓形虫性视乳头炎: 弓形虫性视乳头炎已被作为AIDS的初始症状报道，表现为视力丧失及视神经水肿。可存在相关的脉络膜视网膜炎(18)。疱疹类病毒(水痘，单纯或CMV) 可直接感染视乳头。带状疱疹或单纯疱疹病例中，突然丧失视力的球后视神经炎可在坏死性疱疹性视网膜炎的典型眼底表现前数天出现。乙胺丁醇可致视神经病，特征为色觉减退及视神经苍白。一种视神经炎和去羟肌苷治疗有关(50)。 Progressive Multifocal Leukoencephalopathy (PML): PML commonly affects the visual system with patchy or homonymous visual field defects, visual agnosias, cranial nerve palsies and nystagmus (62). 进行性多灶白质脑病(PML): PML常影响视觉系统，表现为片状或同侧视野缺损，视觉失认，颅神经麻痹及眼球震颤(62)。 Cranial Nerve Palsies: Cranial nerve palsies may be seen in other nervous system diseases such as herpes zoster ophthalmicus (Ramsey-Hunt syndrome), cryptococcal meningitis, cerebral toxoplasmosis, or central nervous system lymphoma (21). In addition, subtle ocular motility defects in patients with AIDS, detected using eye movement recordings, appear directly related to HIV infection of the CNS (61). 颅神经麻痹: Cranial nerve palsies 颅神经麻痹可见于其他神经系统疾病，如眼部带状疱疹(Ramsey-Hunt综合征，耳带状疱疹-膝状神经节综合征)，隐球菌性脑膜炎，脑弓形虫病，或中枢神经系统淋巴瘤(21)。此外，应用眼动记录技术可发现AID患者的微小眼球运动不足，这似乎与CNS的HIV感染直接相关(61)。 Orbital 眼眶 Orbital Aspergillosis: Orbital aspergillosis presents with lid edema and erythema, orbital pain, proptosis, loss of ocular motility and decreased vision (87). The progression of disease may be subacute in AIDS patients as compared with the more chronic course in immunocompetent patients. 眼眶曲霉菌病: 眼眶曲霉菌病表现为眼睑水肿及红斑，眶周疼痛，眼球突出，眼球不能活动及视力减退(87)。AIDS患者的病程进展可为亚急性，而有免疫活性的患者病程相对更慢。 Orbital Lymphoma: Orbital lymphoma can present with a firm palpable orbital mass, periorbital erythema and edema, proptosis and pain. The disease is more aggressive and rapidly progressive in patients with AIDS as compared with lymphoma in immunocompetent hosts (85). 眼眶淋巴瘤: 眼眶淋巴瘤可表现为触及眼眶实性肿物，眶周红斑及水肿，眼球突出及疼痛。和有免疫活性患者的淋巴瘤相比，AIDS患者的该病更具侵袭性，且快速进展(85)。.
RADIOGRAPHIC MANIFESTATIONS Radiologic studies are of limited use in the evaluation of ocular lesions but are extremely useful in neuro-ophthalmic and orbital diseases. Brain MRI is used to identify PML, toxoplasmosis, and CNS lymphoma lesions when there are retrochiasmal visual field defects or associated neurologic signs (62). Orbital computed tomographic scan is used to identify orbital lesions and plan their management. Like most typical orbital lymphomas, the tumor in patients with AIDS will generally conform to the shape of the globe (54). However, a more aggressive form of orbital lymphoma that indents and displaces the globe may be seen in the AIDS population (85). Ophthalmic ultrasonography is useful in defining intraocular lesions in eyes with opaque media. 影像学表现 影像学分析对眼部病变的评估作用有限，但对神经眼科及眼眶疾病非常有用。有视交叉后性视野缺损或相关神经系统体征时，可用头颅MRI鉴别进行性多灶白质脑病（PML），弓形虫病及中枢神经系统（CNS）淋巴瘤病变(62)。眼眶CT扫描可用于确定眼眶病变及制定处理计划。AIDS患者的肿瘤和大多数典型的眼眶淋巴瘤一样，通常顺应眼球形态(54)。但是， 一种更具侵袭性的眼科淋巴瘤可见于AIDS人群，它们可以嵌入眼球并使其移位(85)。眼科超声波扫描有助于定位介质不透明眼的眼内病变。
DIAGNOSIS 诊断 Asymptomatic Patients The optimal interval for screening eye examinations is unknown. The incidence of CMV retinitis in patients with CD4+ lymphocyte counts < 100 is high enough to warrant complete eye examinations every 6 to 12 months. 无症状患者 眼部筛查的最佳时间间隔尚不清楚。CD4+淋巴细胞计数< 100的患者CMV性视网膜炎的发病率非常高，需确保每6-12月进行一次全面的眼科检查。 Symptomatic Patients Whereas a simple refraction will suffice to diagnose blurred near vision related to presbyopia, most patients with AIDS should receive a complete eye examination if ocular complaints are present. 有症状的患者 尽管简单的屈光检查足以诊断老花相关的近视力模糊，大多数AIDS患者若有眼部不适时，还应当接受全面的眼科检查。 Eyelid Lesions: Diagnosis of the lesions is based primarily on their clinical appearance. Fluid from vesicles suspected to be secondary to herpes zoster or simplex can be sent for specific immunofluorescent staining to confirm the diagnosis. 眼睑病变: 病变的诊断主要根据其临床表现。怀疑继发于带状或单纯疱疹的液性囊泡可送检特异性免疫荧光染色以确诊。 Anterior Segment: Actinic changes that do not require biopsy (pterygia or pingueculae) can be diagnosed by an ophthalmologist by their appearance. Both conjunctivitis in AIDS patients and infectious corneal ulcers may require specialized cultures from the ocular surface by an ophthalmologist. Measurement of the rate of tear production under controlled conditions by the wetting of special filter paper strips (Schirmer’s test) is useful in the diagnosis of keratitis sicca. A determination of drug-induced uveitis is made on the basis of medication history and slit lamp findings. 前节:光化学改变无需活检(翼状胬肉或睑裂斑)，眼科医师根据其外观即可诊断。AIDS患者的结膜炎及感染性角膜溃疡可能需要眼科医师从眼表取样进行专科培养。在限定的条件下以浸湿特异性滤纸条(Schirmer’s实验) 的方式测量泪液流率有助于诊断干燥性角膜炎。药物性葡萄膜炎是根据用药史及裂隙灯检查结果确定的。 Retina and Choroid: Diagnosis of diseases of the retina and choroid is made ophthalmoscopically by an experienced observer. An approach to screening and diagnosis of CMV retinitis is depicted in Figure 1 (11). The reduction in cases of CMV retinitis has made diagnosis somewhat more challenging as the relative percentage of other types of retinitis has increased. RPR, FTA-Abs, PPD, CXR, and Bartonella henselae serum antibody titers can be helpful in confirming specific infectious etiologies. 视网膜及脉络膜:有经验的医师可用眼底镜诊断视网膜及脉络膜病变。一种筛查及诊断CMV性视网膜炎的方法在图1(11)进行了描述。CMV性视网膜炎病例的减少使其诊断更具挑战性，因为其它类型视网膜炎的相对百分比增加了。RPR，FTA-Abs，PPD，CXR及亨氏巴尔通体血清抗体滴度可帮助确定特异性感染源。 Neuro-Ophthalmic: Clinical exam along with proper imaging as described above is often sufficient for diagnostic purposes. Particular attention should be given to the eye movements (ductions and saccades) during the exam. PML-related visual field defects are best detected by Goldmann 60-degree visual field testing, which is generally available only in academic centers. 神经眼科:前述的临床检测连同特有的影像通常足以诊断。检查过程中应特别关注眼球运动（转向及眼跳）。最好以Goldmann 60度视野测试查出进行性多灶白质脑病(PML)相关性视野缺损，但通常仅能在学术中心进行。 Orbital: Eye movements are often restricted in orbital disease. Mass lesions may produce a notable protrusion of the globe, swelling, or congestion. Palpation within the orbital rim can sometimes detect the anterior edge of a retroorbital mass. 眼眶:眼眶病变时眼球运动通常受限。块状病变可使眼球明显突出，肿胀或充血。眶缘触诊有时可发现眶后肿块的前缘。 Invasive Diagnostic Tests 有创性诊断性检查 Eyelid Lesions: Incisional or excisional biopsies of eyelid lesions can be used to obtain material for histopathology if the diagnosis is unclear from clinical appearance. Curettage of molluscum lesions can be also submitted for histopathology. 眼睑病变: 如果临床表现不能明确诊断，切开或切除活检眼睑病变可获取组织病理学材料。刮取软疣病变亦可送检组织病理学。 Anterior Segment: Conjunctival neoplasms require excisional biopsy for diagnosis by an experienced ophthalmic pathologist for proper diagnosis. Corneal biopsy is needed only rarely for infectious ulcers when they are unresponsive to conventional treatment and/or cultures are unrevealing or equivocal. 前节: 结膜新生物需由有经验的眼科病理医师行切除活检以作出正确的诊断。角膜活检仅在感染性溃疡对常规治疗无反应及/或培养阴性或可疑时需要进行。 Retina and Choroid: Removal of aqueous and/or vitreous humor for PCR (polymerase chain reaction) assay, antibody detection or culture may be indicated when an infectious etiology is suspected and the diagnosis is unclear based on clinical appearance. This should be performed by an experienced ophthalmologist. Severely involved eyes with previously undescribed manifestations, or in which bacterial or fungal involvement is suspected will generally require diagnostic vitrectomy with extensive cultures, PCR studies, and possibly retinal biopsy. The volume of vitreous available for analysis is much greater in this method and thus more likely to yield a positive result. Diagnostic tests are also commonly performed in conjunction with a therapeutic surgical intervention, such as retinal detachment repair. 视网膜及脉络膜:当怀疑某种感染源且仅依靠临床表现不能明确诊断时，取房水和/或玻璃体进行PCR（聚合酶链反应）化验，抗体检测或培养可能能指明问题。这应由有经验的眼科医师操作。有前文未描述表现的严重受累眼，或怀疑有细菌或真菌感染时，通常需要进行诊断性玻璃体切除取材进行广谱培养，PCR研究，还可能需要视网膜活检。这种方法可取的用于分析的玻璃体量太大，因此更可能产生阳性结果。诊断性检查的操作也常与治疗性手术干预相结合，如视网膜脱离的修复。 In AIDS patients with active, untreated CMV retinitis, the PCR-based assay performed on vitreous obtained during a surgical procedure is 95% sensitive (56). If the patient has already received treatment, the sensitivity declines to 47.5%. PCR for detection of VZV and HSV in the vitreous is also useful for distinguishing between the causes of viral retinitis when the diagnosis is unclear clinically (47). In the investigation of necrotizing retinitis, comparative serology in the aqueous or vitreous with serum for antibodies against toxoplasmosis, CMV, herpes simplex and VZV may be helpful as well (11). However, antibody determinations are probably less useful than PCR in patients with AIDS because of an inconsistent immune response. 未经治疗的活动性CMV性视网膜炎的AIDS患者在手术过程中所取玻璃体进行PCR化验的敏感性为95%(56)。如果患者已经接受了治疗，敏感性降至47.5%。应用PCR检测玻璃体中的VZV及HSV也有助于在临床诊断不明确时鉴别病毒性视网膜炎的病因(47)。研究坏死性视网膜炎时，房水或玻璃体对比血清的抗弓形虫，CMV，单纯疱疹及VZV抗体的比较血清学检查可能也有帮助(11)。但是，AIDS患者的抗体测定可能没PCR有用，因为他们的免疫应答不一致。 Neuro-Ophthalmic: Lumbar puncture should be performed to confirm the diagnosis when a CNS lesion or infection is present. The studies ordered will depend on the clinical and radiologic appearance of the lesion and could include cryptococcal antigen, JC virus cultures for PML, and cytology for lymphoma. Orbital: Incisional biopsy for suspected lymphoma should be performed. Fine needle aspiration of an Aspergillus abcess is performed with examination of the fluid for hyphal elements (87). 神经眼科:中枢神经系统（CNS）病变或感染时应行腰椎穿刺检查以明确诊断。检查要根据病变的临床及影像学表现来安排，可包括隐球菌抗原检查，针对PML的JC病毒培养及针对淋巴瘤的细胞学检查。眼眶:怀疑淋巴瘤时应行切开活检。对于曲霉菌脓肿可以用细针穿刺检查菌丝的存在(87)。
MANAGEMENT 治疗 Table 1 summarizes drug therapies for various HIV ocular complications. 表1 概述了多种HIV眼部并发症的药物疗法。 Eyelid Lesions Removal of molluscum contagiosum lesions by surgery and cryotherapy appears to be of limited long-term benefit in patients with AIDS, as the disease usually recurs within 6 to 7 weeks (69). Successful treatment of molluscum lesions in HIV positive patients using topical imiquimod and intravenous or topical cidofovir has been reported in the dermatologic literature (51, 89). Imiquimod can only be used on the eyelid itself and not at the eyelid margin. Maintenance therapy is often required. A single treatment of 800 cGy radiotherapy has been shown to be effective, safe palliative therapy for ocular Kaposi sarcoma with only a 22% recurrence rate (27). Cryotherapy of lid lesions is effective with early (stage I and II) lesions but is associated with recurrence in stage III lesions (14). Observation is also a reasonable option (2). HIV positive patients with herpes zoster ophthalmicus should be treated with a 7-day course of high-dose (30mg/kg/day) intravenous acyclovir followed by oral therapy to minimize serious neurologic complications (74). 眼睑病变 通过手术及冷冻疗法清除传染性软疣病变似乎对AIDS患者的长期有效性有限，因为该病常在6-7周内复发 (69)。 皮肤病学文献已有报道，应用局部咪喹莫特及静脉内或局部西多福韦可成功治疗HIV阳性患者的软疣病变(51,89)。咪喹莫特仅可用于眼睑本身，而不能用于睑缘。通常需要维持治疗。 单纯应用800 cGy放射线治疗已显示有效，对眼部卡波西肉瘤进行安全的姑息疗法仅有22%的复发率(27)。眼睑病变的冷冻疗法对早期(I期和II期)病变有效，但与III期病变的复发相关(14)。观察也是一种合理的选择(2)。 有眼部带状疱疹的HIV阳性患者应先以高剂量(30mg/kg/天) 静脉内阿昔洛韦治疗7天，再口服治疗，将神经性并发症的严重程度减至最轻(74)。 Anterior Segment CIN in AIDS patients is effectively treated with excision (41). Topical application of Mitomycin C and interferon alpha-2b have also shown efficacy in non-AIDS patients, but their role in the HIV-positive population, in which the disease tends to be more aggressive, is untested (22, 44, 86). As with the adnexal form of the disease, AIDS-related conjunctival Kaposi sarcoma can be adequately controlled with radiotherapy (7, 27). Interferon alpha-2b has also been shown to be effective (35). The treatment of infectious corneal ulcers is directed by culture results. It is important to provide empiric anti-pseudomonal coverage for bacterial ulcers until culture results are available because of the aggressive course of pseudomonal ulcers in HIV patients (60). Herpes zoster and simplex keratitis are treated with topical antivirals until epithelial healing takes place. Maintenance therapy with oral antiviral therapy may be important in HIV patients because of the higher recurrence rate in this group (31). Topical fumagillin and dibromopropamidine ointment (neither of which are approved for human use in the United States) are safe agents for the treatment of microsporidial keratoconjunctivitis (25, 57). Frequent artificial tears and punctal occlusion are usually sufficient to control the symptoms of keratitis sicca. Drug-induced uveitis is treated by stopping the offending agent and using a topical steroid and cycloplegic. Visual acuity may not return to the previous level in cidofovir-associated uveitis despite resolution of inflammation (12). 前节 切除术可有效治疗AIDS患者的CIN (结膜上皮内瘤)(41)。局部应用丝裂霉素C及干扰素α-2b也已在非AIDS患者中显示出其功效，但对HIV阳性人群的作用未经试验，而该病在HIV人群进展更迅速(22, 44, 86)。 和其他部位的卡波西肉瘤一样，放疗可以充分控制AIDS相关性结膜卡波西肉瘤(7, 27)。干扰素α-2b也已显示出其有效性(35)。 感染性角膜溃疡的治疗应根据培养结果进行。得到培养结果前对于细菌性溃疡进行经验性抗假单胞菌覆盖治疗很重要，因为HIV患者的假单胞菌性溃疡病程进展迅速(60)。带状疱疹及单纯疱疹性角膜炎应进行局部抗病毒治疗，直到上皮恢复。口服抗病毒药维持治疗对HIV患者可能很重要，因为他们复发率更高(31)。局部烟曲霉素及双溴丙脒眼膏(二者用于人类都未经美国认可)都是治疗微孢子虫性角结膜炎的安全药物(25, 57)。 频繁应用人工泪液及泪点栓塞通常足以控制干燥性角膜炎的症状。药物性葡萄膜炎可通过停止给药并局部应用激素及睫状肌麻痹剂来治疗。尽管炎症消退，视力可能无法恢复到原先的水平(12)。 Retina and Choroid 视网膜及脉络膜 Treatment for HIV retinopathy is immune reconstitution via HAART. HIV性视网膜病的治疗是通过HAART进行免疫重建。 The treatment of CMV retinitis has changed rapidly over the past few years with introduction of new agents (See Table 2). Figure 2 displays our current therapeutic recommendations. Induction therapy at an initial high dose is followed by lower dose maintenance therapy that presumably decreases side effects. The gold standard for induction therapy has been intravenous ganciclovir 5mg/kg BID for 2 – 3 weeks. Foscarnet can also be used for induction, but is less well tolerated (81). Valganciclovir, the oral prodrug of ganciclovir approved by the FDA in April 2001, is rapidly absorbed and provides high oral bioavailability. Oral valganciclovir 900 mg BID for 3 weeks is equivalent to induction therapy with intravenous ganciclovir for the same period (9). Oral induction makes outpatient induction a possibility, however, hospitalization may be preferable for some patients with multiple problems to permit treatment in a structured environment. 随着新药物的引进，CMV性视网膜炎的治疗在过去的几年里变化迅速(见表2)。图2显示了目前推荐的治疗方法。初始高剂量诱导治疗，而后低剂量维持治疗可以降低副作用。诱导治疗的金标准为静脉内更昔洛韦5mg/kg BID 2-3周。膦甲酸也可用于诱导，但其可耐受性略差(81)。2001年4月FDA认可的口服更昔洛韦药物前体缬更昔洛韦，可以快速吸收，有着高的口服生物利用度。口服缬更昔洛韦900 mg BID 3周相当于静脉内更昔洛韦3周的诱导治疗(9)。口服诱导使门诊患者诱导治疗成为可能，但是，一些多重问题的患者可能住院更好，这样可以在一个整体环境中进行治疗。 After induction, therapy is determined by whether the patient is HAART naïve or HAART experienced and failing treatment. In HAART naïve patients who are beginning potent antiretroviral therapy, oral maintenance therapy with oral valganciclovir 900 mg daily is preferred. Daily intravenous ganciclovir 5 mg/kg, intermittent intravenous cidofovir 3-5 mg/kg every 2 weeks, or intravenous foscarnet 90 - 120 mg/kg daily can be used in patients who cannot take oral therapy. The intravenous maintenance regimens offer no particular benefit over oral valganciclovir although the periodic cidofovir infusions provide a way to monitor compliance to treatment and can usually be given without implantation of a central venous catheter. 诱导后的治疗由患者是否未经HAART还是经历过HAART但治疗失败决定。开始有效的抗逆转录病毒治疗的未经HAART的患者，首选每日口服缬更昔洛韦900 mg的口服维持治疗。每日静脉内更昔洛韦5 mg/kg，每两周间断静脉内西多福韦3-5 mg/kg，或每日静脉内膦甲酸90 - 120 mg/kg可用于不能口服治疗的患者。尽管定期输注西多福韦提供了监控治疗相关并发症的方法，且通常不需植入中央静脉导管即可输注，但静脉内维持方案和口服缬更昔洛韦相比并无特殊益处。 Patients failing HAART who develop CMV retinitis will often have poor response to maintenance therapy, similar to patients of the pre-HAART era in 50% of whom there was recurrence of active CMV retinitis within 60 days of beginning anti-CMV therapy (81). Therefore, patients with sight-threatening CMV retinitis in whom immune recovery is not anticipated may benefit from implantation of the ganciclovir intraocular device at the time of diagnosis of CMV retinitis or by use of the ganciclovir implant as maintenance therapy after a course of systemic induction. Systemic induction treatment prior to ganciclovir implant placement allows formation of stable chorioretinal scars, which may reduce the risk of retinal detachment, and permits the treatment of extraocular foci of disease. Some form of systemic anti-CMV therapy (usually oral ganciclovir or valganciclovir) is indicated in virtually every patient after implantation of the ganciclovir intraocular device to prevent systemic disease or infection of the fellow eye (55). 发生CMV性视网膜炎的HAART 失败患者通常对维持疗法反应较弱，与HAART 出去前的患者相似，其中50%在开始抗CMV治疗60天内复发活动性CMV性视网膜炎(81)。因此，一经诊断CMV性视网膜炎即植入眼内更昔洛韦埋植剂，或在系统性诱导疗程后应用更昔洛韦埋植剂维持治疗，对免疫力未能按预期恢复，视力受到威胁的CMV性视网膜炎患者可能有益。更昔洛韦埋植剂置入前的系统性诱导治疗有利于稳定的脉络膜视网膜瘢痕形成，这可以降低视网膜脱离的风险，并有利于眼外病灶的治疗。事实上每位植入眼内更昔洛韦埋植剂的患者都显示需要某种方式的系统性抗CMV治疗（通常为口服更昔洛韦或缬更昔洛韦），以预防系统性疾病或对侧眼的感染(55)。 Determination of the retinitis status is made by ophthalmologic examination every 1 to 2 months. If recurrent disease develops, change in therapy is indicated. Reinduction with the same drug or switching to another monotherapy is ineffective, although cidofovir has not been formally tested. Combination therapy with both ganciclovir and foscarnet is more successful than reinduction with either drug alone but is a highly burdensome treatment and only produces a remission of 4 to 5 months before the retinitis recurs again (80). The ganciclovir intraocular device has a much longer time to recurrence than systemic therapy and achieves four-fold higher intraocular ganciclovir levels than intravenous ganciclovir (29, 59). Implantation is optimal if it is performed at the first recurrence as there is only a 50% success rate with implantation if prior exposure to ganciclovir exceeds six months (71). If viral resistance is not present, the ganciclovir intraocular device should maintain remission for 6 to 8 months, which is the expected duration of the drug depot. 每1-2月一次眼科检查可确定视网膜状态。如果疾病复发，表示需要更改治疗。应用同种药物或其它单一疗法进行再次诱导无效，尽管西多福韦尚未正式测试。更昔洛韦及膦甲酸联合疗法比单用其中一种药物再诱导更有效，但负担很重，且仅能维持4-5月不复发(80)。眼内更昔洛韦埋植剂比系统疗法的不复发期长很多，且比静脉内更昔洛韦后眼内更昔洛韦水平高出1/4(29, 59)。初次复发即植入最佳，因为如果此前暴露于更昔洛韦超过6个月，成功率仅有50%(71)。如果没有病毒耐受，眼内更昔洛韦埋植剂应能维持6-8月不复发，这是所储药物的预期持续时间。 For patients failing standard regimens, there are several strategies depending on the current therapy. If the patient already has an intravitreal ganciclovir implant, then intravenous foscarnet or off-label intravitreal injections of foscarnet 1.2 to 2.4 mg in 0.1 ml may be helpful (13). Combination injections of ganciclovir 2.0 mg (88) and foscarnet 1.2 mg are also a potent off-label form of salvage therapy. Intravenous cidofovir combined with probenecid is useful in recurrent disease but displays some cross resistance with ganciclovir. Anterior uveitis and alterations in intraocular pressure may occur with cidofovir (12,65). Intravitreous injections are administered by an experienced ophthalmologist in the office setting under topical anesthesia from twice a week to monthly depending on agent and are essentially painless. 一些依赖于现有疗法的策略可用于标准方案失败的患者。如果患者已经有了玻璃体内更昔洛韦埋植剂，静脉内膦甲酸或药物许可适应症以外静脉内注射膦甲酸1.2 -2.4 mg in 0.1 ml可能有帮助(13)。联合注射更昔洛韦2.0 mg (88)及膦甲酸1.2 mg也是有效的药物适应症以外的抢救方式。静脉内西多福韦联合丙磺舒对复发病变有效，但与更昔洛韦有部分交叉耐受。 应用西多福韦后可发生前部葡萄膜炎及眼压变化(12,65)。玻璃体腔内注射于专科环境中由有经验的眼科医师在局部麻醉下进行，根据药物选择每周2次到每月1次，基本无痛。 Recent data demonstrate an association between CMV load and both CMV retinitis progression and the occurrence of resistant CMV (36). Despite the strong association between CMV load and these outcomes, the clinical utility of a high CMV load is limited because of its low positive predictive value for these outcomes. However, the negative predictive value of CMV load for occurrence of resistant CMV is good (i.e., if a patient’s viral load is low, it is unlikely they harbor resistant CMV). Because CMV load testing results can be obtained within one day, whereas conventional CMV susceptibility testing takes weeks, it may be a useful screening tool for determination of whom to test for resistant CMV by use of more conventional means. 近来有数据证明CMV载量与CMV性视网膜炎的进展及耐药CMV的发生都有关(36)。尽管CMV载量与这些结果联系紧密，但高CMV载量的临床效用有限，因为它对这些结果的阳性预测价值较低。但是，CMV载量对发生耐药CMV的阴性预测价值很好(如，如果患者的病毒载量低，他们不可能患有耐药CMV)。因为CMV载量检查一天内即可获得结果，而传统的CMV敏感性检查需要数周，所以它可作为有效的筛查工具来决定谁需要用更传统方法来检查耐受性CMV。 Patients with good response to HAART therapy may be considered for withdrawal from specific anti-cytomegalovirus therapy after the CD4+ T lymphocyte count has been maintained at roughly 150 cells/mm3 for 3 months or so (53). Consideration of the viral load and the CD4+ T lymphocyte count at the time of diagnosis of CMV retinitis helps predict which patients can be successfully withdrawn. Later reduction in CD4+ T lymphocyte count to 50 cells/mm3 requires resumption of maintenance therapy. 对HAART疗法反应很好的患者在CD4+ T淋巴细胞计数维持于大约150个细胞/mm3 3个月或左右后，可考虑撤除特异性抗巨细胞病毒治疗(53)。诊断CMV性视网膜炎时考虑病毒载量及CD4+ T淋巴细胞计数有助于预测哪些患者可以成功撤药。撤药后 CD4+ T淋巴细胞计数减少到50个细胞/mm3时需要重新开始维持治疗。 Reports of the course of CMV retinitis in the HAART era show that the rate of retinitis progression is decreased compared to the pre-HAART era, even among those with low CD4+ T cell counts (37). However, retinitis progression still occurs, even among patients with high CD4+ T-cell counts and presumed immune recovery. Rates of second eye involvement and retinal detachment are also reduced in the HAART era (38). However, among patients with CD4+ T-cell counts of < 50 μL, the rates were more similar to those from the pre-HAART era. Continued ophthalmologic follow-up of patients with immune recovery is recommended to detect early retinitis progression, second eye involvement, and complications such as retinal detachment. HAART后的CMV性视网膜炎病进展速度与HAART前相比下降，即使其中CD4+ T细胞计数低的也是如此(37)。但是，视网膜炎仍会进展，即便是那些CD4+ T细胞计数较高，免疫恢复的患者。第二只眼受累和视网膜脱离的速度在HAART后也有所降低(38)。但是，CD4+ T细胞计数< 50 µL的患者的进展速度更类似HAART治疗前的速度。建议持续眼科随访患者的免疫恢复情况，以早期发现视网膜炎的进展，第二只眼的受累及视网膜脱离等并发症。 Immune recovery uveitis can produce visual problems in patients who would have otherwise tolerated their CMV infection quite well. Visual acuity improvement has been documented after treatment with oral prednisone or periocular injection (43). In another study, vitritis and vision improved within six weeks regardless of whether or not anti-inflammatory therapy was given (90). Corticosteroid therapy of immune recovery uveitis has not been reported to cause reactivation of CMV retinitis lesions in patients with elevated CD4 counts (33). CMV retinitis can also be complicated by retinal detachment that requires prompt surgical repair (24, 82). 免疫重建性葡萄膜炎可使部分患者产生视力受损，其他患者则可很好地耐受CMV感染。已证实口服泼尼松或眼旁注射治疗后视力有改善(43)。另一项研究发现，无论是否给予抗炎治疗，玻璃体炎及视力在6周后都有改善(90)。糖皮质激素治疗不会导致在CD4计数升高的患者中CMV性视网膜炎再次活动(33)。CMV性视网膜炎还可并发视网膜脱离，需要及时手术修复(24, 82)。 Necrotizing herpetic retinitis requires immediate, aggressive therapy in all HIV patients regardless of immune status. Since the infection can progress rapidly to blindness, it is preferable to over-treat rather than risk an irretrievable failure. Combination intravenous antiviral therapy consisting of intravenous foscarnet and ganciclovir is often successful whereas intravenous acyclovir often fails (78). The use of intravitreal injections of combined ganciclovir 2.0 mg and foscarnet 1.2 mg up to 3 times per week for two weeks, then once or twice weekly until healed will benefit some patients (52). Laser demarcation of all areas of retinitis may reduce the risk of retinal detachment. Lifetime suppressive antiviral medication may be needed although this is less clear than with cytomegalovirus. Oral valganciclovir or oral valacyclovir might be sufficient after an initial prolonged course intravenous therapy. Removal of intraocular fluid for viral diagnostic studies in the acute phase is useful as herpes zoster would be predicted to require higher drug doses in maintenance than herpes simplex. 不管免疫状态如何，所有HIV患者的坏死性疱疹性视网膜炎都需要立刻积极治疗。这种感染可以快速进展致盲，所以宁可过度治疗，也不要冒无可挽回性失败的风险。由静脉内膦甲酸及更昔洛韦组成的联合静脉内抗病毒疗法通常有效，而静脉内阿昔洛韦常有治疗失败(78)。 玻璃体内注射联合更昔洛韦2.0 mg及膦甲酸1.2 mg 每周3次共两周，然后每周1次或两次，直到治愈，对一些患者有效(52)。激光划清所有视网膜炎区域界限可减少视网膜脱离的危险。可能需要终生应用抑制性抗病毒药物，尽管不像在CMV感染中那么常见. 初始长期静脉内疗程，而后口服缬更昔洛韦或伐昔洛韦可能已足够。急性期取眼内液体进行诊断性研究很有用，因为可以区分是否为带状疱疹，而它比单纯疱疹的维持治疗需要的药物剂量更高。 Treatment of toxoplasmic chorioretinitis with pyrimethamine, sulfadiazine, and clindamycin is effective in over 75% of patients (23). Corticosteroid treatment is unnecessary. Innovative treatment regimens with atovoquone 750 mg TID and clarithromycin 500 mg po BID can be considered for patients with sulfa allergy (42). Once resolution occurs, maintenance therapy is continued as relapses occur in the absence of treatment. Trimethoprim-sulfamethoxazole provides adequate prophylaxis against recurrence. 乙胺嘧啶，磺胺嘧啶及克林霉素治疗弓形虫性脉络膜视网膜炎对75%以上的患者有效(23)。不必应用糖皮质激素治疗。对磺胺类药过敏的患者可考虑应用阿托伐醌750 mg TID及克拉霉素500 mg po BID的创新型治疗方案(42)。一旦炎症消退，继以维持治疗，因为治疗中断可致复发。甲氧苄啶-磺胺甲口恶唑可充分预防复发。 Intravenous trimethoprim and sulfamethoxazole and parenteral pentamidine result in resolution of pneumocystis choroidal lesions (15). Systemic prophylaxis with Dapsone or trimethoprim-sulfamethoxazole effectively prevents recurrence (76). Syphilitic chorioretinitis in HIV patients is treated with intravenous penicillin according to the CDC recommendations for neurosyphilis (intravenous aqueous penicillin G, 24 million units per day, for 10 days OR intramuscular procaine pencillin G, 2.4 million units per day, for 10 days with probenecid 500 mg po QID). Appropriate anti-tuberculous therapy, such as a combination of isoniazid, rifampin and ethambutol, can result in healing of ocular lesions of tuberculous choroiditis (58). Doxycycline and rifampin appear to shorten the course of disease and hasten visual recovery in Bartonella retinitis (67). In patients with AIDS and Bartonella infection, a 1-month to 4-month course of erythromycin or doxycycline has also been recommended (40). 静脉内甲氧苄啶，磺胺甲口恶唑及肠外喷他脒可使肺孢子虫性脉络膜病变消退(15)。应用氨苯砜或甲氧苄啶-磺胺甲口恶唑进行系统性预防可以有效防止复发(76)。根据美国疾病控制中心对神经梅毒的建议以青霉素治疗HIV患者的梅毒性脉络膜视网膜炎(静脉青霉素G，2400万单位每天共10天；或肌注普鲁卡因青霉素G，240万单位每天共10天，同时丙磺舒500 mg po QID)。适当的抗结核治疗，如异烟肼，利福平及乙胺丁醇，可使结核性脉络膜炎的眼部病变康复(58)。多西环素及利福平似乎可以缩短巴尔通体性视网膜炎的病程，并加速视力的恢复(67)。1个月或4个月的红霉素或多西环素疗程也建议用于感染了巴尔通体的AIDS患者(40)。 Fungal endophthalmitis usually required intraocular treatment with amphotericin and debridement by vitrectomy. Intravenous amphotericin or oral fluconazole may adequately treat choroidal infections that have not penetrated into the vitreous cavity. Bacterial endophthalmitis can sometimes be treated solely with systemic antibiotics if the patient is debilitated and cannot undergo eye surgery. When possible, vitrectomy, culture, and injection of broad-spectrum intravitreal antibiotics are preferred. 真菌性眼内炎通常需要眼内治疗，需行玻璃体切除术清除，并应用两性霉素。静脉内两性霉素或口服氟康唑可充分治疗未侵入玻璃体腔的脉络膜感染。细菌性眼内炎患者如果很虚弱，不能承受眼部手术，有时也可单用系统性抗生素治疗。如有可能，首选玻璃体切除术，培养并玻璃体腔内注射广谱抗生素。 External beam radiation has been used in the treatment of AIDS-related intraocular lymphoma but efficacy is difficult to determine as patients have died from other AIDS complications before completion of therapy (68). Chemotherapy is also an option. Intravitreal methotrexate has been used as an adjunctive therapy in the treatment of intraocular lymphoma in non-AIDS patients (19). 体外放射治疗已用于AIDS相关性眼部淋巴瘤的治疗，但其疗效难以明确，因为患者在完成治疗前已死于其它AIDS并发症(68)。化疗也是种选择。玻璃体内甲氨喋呤已被用于非AIDS患者的辅助治疗(19)。 Neuro-ophthalmic IV Amphotericin (0.8 –1.5 mg/kg/day) followed by oral fluconazole (200 mg/day) has been shown to decrease the relapse rate of cryptococcal meningitis in AIDS patients (79). Toxoplasma papillitis should be treated with appropriate anti-parasitic therapy (32). No effective therapy for PML has been found to date. 神经眼科 IV两性霉素(0.8 –1.5 mg/kg/day)，随后口服氟康唑(200 mg/day)已显示可降低AIDS患者隐球菌性脑膜炎的复发速率(79)。弓形虫性视乳头炎应进行适当的抗寄生虫治疗(32)。进展性多灶白质脑病(PML) 至今尚无有效治疗。 Orbital Incision and drainage of an aspergillus abscess in conjunction with local and systemic amphotericin can achieve resolution of disease in HIV positive patients (87). Orbital lymphoma does show at least a short-term response to radiotherapy (54). 眼眶 切开引流曲霉菌性脓肿联合局部及系统性两性霉素可使HIV阳性患者的病变消退(87)。眼眶淋巴瘤对放疗至少显示出短期反应(54)。
TABLES AND FIGURES Table 1. Drugs for Treatment of HIV Ocular Complications [Download PDF] Table 2. Treatment of CMV retinitis: dosing and toxicities [Download PDF] Figure 1. Diagnostic Algorithm for CMV Retinitis Figure 2. Treatment Algorithm for CMV retinitis 表1. 治疗HIV眼部并发症的药物[下载 PDF]
表2. CMV性视网膜炎的治疗: 药物剂量与毒性[下载PDF]
图1. CMV性视网膜炎的诊断流程
图2. CMV性视网膜炎的治疗流程
REFERENCES 1. Arevalo JF, Quiceno JI,
Garcia RF, McCutchan JA, Munguia D, Nelson JA, Freeman WR. Retinal findings and
characteristics in AIDS patients with systemic Mycobacterium
avium-intracellulare complex and toxoplasmic encephalitis. Ophthalmic Surg
Lasers 1997; 28: 50-4. 2. Brun SC, Jakobiec FA. Kaposi’s sarcoma of the ocular adnexa. Int Ophthalmol Clin 1997; 37: 25-38.[Pub Med] 3. Chavez-de la Paz E, Arevalo JF, Kirsch LS, Munguia D, Rahhal FM, De Clerq E, Freeman WR. Anterior nongranulomatous uveitis after intravitreal HPMPC (cidofovir) for the treatment of cytomegalovirus retinitis; analysis and prevention. Ophthalmology 1997;104:539-44.[Pub Med] 4. Chern KC, Conrad D, Holland GN, Holsclaw DS, Schwartz LK, Margolis TP. Chronic varicella-zoster virus epithelial keratitis in patients with acquired immunodeficiency syndrome. Arch Ophthalmol 1998;116:1011-7.[Pub Med] 5. Cohen DB, Glasgow BJ. Bilateral optic nerve cryptococcosis in sudden blindness in patients with acquired immune deficiency syndrome. Ophthalmology 1993;100:1689-94.[Pub Med] 6. Cole EL, Meisler DM, Calabrese LH, Holland GN, Mondino BJ, Conant MA. Herpes zoster ophthalmicus and acquired immune deficiency syndrome. Arch Ophthalmol 1984;102:1027-9. [Pub Med] 7. Cooper JS, Fried PR. Treatment of aggressive epidemic Kaposi’s sarcoma of the conjunctiva by radiotherapy. Arch Ophthalmol 1988;106:20-1. [Pub Med 8. Culbertson WW, Blumenkranz MS, Pepose JS, Stewart JA, Curtin VT. Varicella zoster virus is a cause of the acute retinal necrosis syndrome. Ophthalmology 1986; 93: 559-68; discussion by LM Jampol, 556-569. [Pub Med] 9. Curran M, Noble S. Valganciclovir. Drugs 2001;61:1145-50; discussion 1151-1152. [Pub Med] 10. Davis JL. An algorithmic approach to treatment of cytomegalovirus retinitis. Semin in Ophthalmol 1995;10:119-24. [Pub Med] 11. Davis JL, Feuer W, Culbertson WW, Pflugfelder SC. Interpretation of intraocular and serum antibody levels in necrotizing retinitis. Retina 1995;15:233-40. [Pub Med] 12. Davis JL, Taskintuna I, Freeman WR, Weinberg DV, Feuer WJ, Leonard RE. Iritis and hypotony after treatment with intravenous cidofovir for cytomegalovirus retinitis. Arch Ophthalmol 1997;115:733-7. [Pub Med] 13. Díaz-Llopis M, Chipont E, Sanchez S, España E, Navea A, Menezo JL. Intravitreal foscarnet for cytomegalovirus retinitis in a patient with acquired immunodeficiency syndrome. Am J Ophthalmol 1992; 114: 742-7. [Pub Med] 14. Dugel PU, Gill PS, Frangieh GT, Rao NA. Treatment of ocular adnexal Kaposi’s sarcoma in acquired immune deficiency syndrome. Ophthalmology 1992;99:1127-32. [Pub Med] 15. Dugel PU, Rao NA, Forster DJ, Chong LP, Frangieh GT, Sattler F. Pneumocystis carinii choroiditis after long-term aerosolized pentamidine therapy. Am J Ophthalmol 1990;110:113-7. [Pub Med] 16. Engstrom RE Jr, Holland GN. Chronic herpes zoster virus keratitis associated with the acquired immunodeficiency syndrome. (letter) Am J Ophthalmol. 1988;105:556-8. [Pub Med] 17. Engstrom RE Jr, Holland GN, Margolis TP, Muccioli C, Lindley JI, Belfort R Jr, Holland SP, Johnston WH, Wolitz RA, Kreiger AE. The progressive outer retinal necrosis syndrome; a variant of necrotizing herpetic retinopathy in patients with AIDS. Ophthalmology 1994;101:1488-502. [Pub Med] 18. Falcone PM, Notis C, Merhige K. Toxoplasmosis papillitis as the initial manifestation of acquired immunodeficiency syndrome. Ann Ophthalmol 1993;25:56-7. [Pub Med] 19. Fishburne BC, Wilson DJ, Rosenbaum JT, Neuwelt EA. Intravitreal methotrexate as an adjunctive treatment of intraocular lymphoma. Arch Ophthalmol 1997;115:1152-6. [Pub Med] 20. Freeman WR, Lerner CW, Mines JA, Lash RS, Nadel AJ, Starr MB, Tapper ML. A prospective study of the ophthalmologic findings in the acquired immune deficiency syndrome. Am J Ophthalmol 1984;97:133-42. [Pub Med] 21. Friedman DI. Neuro-ophthalmic manifestations of human immunodeficiency virus infection. Neurol Clin. 1991;9:55-72. [Pub Med] 22. Frucht-Pery J, Sugar J, Baum J, Sutphin JE, Pe’er J, Savir H, Holland EJ, Meisler DM, Foster JA, Folberg R, Rozeman Y. Mitomycin C treatment for conjunctival-corneal intraepithelial neoplasia; a multicenter experience. Ophthalmology 1997; 104:2085-93; discussion by PR Laibson, 2093. [Pub Med] 23. Gagliuso DJ, Teich SA, Friedman AH, Orellana J. Ocular toxoplasmosis in AIDS patients. Tr Am Ophthalmol Soc 1990; 88:63-86; discussion, 86-88. [Pub Med] 24. García RF, Flores-Aguilar M, Quiceno JI, Capparelli EV, Munguia D, Kuppermann BD, Arevalo F, Freeman WR. Results of rhegmatogenous retinal detachment repair in cytomegalovirus retinitis with and without scleral buckling. Ophthalmology 1995;102:236-245. [Pub Med] 25. Garvey MJ, Ambrose PG, Ulmer JL. Topical fumagillin in the treatment of microsporidial keratoconjunctivitis in AIDS. Ann Pharmacother 1995;29:872-4. [Pub Med] 26. Geier SA, Libera S, Klauss V, Goebel FD. Sicca syndrome in patients infected with the human immunodeficiency virus. Ophthalmology 1995;102:1319-24. [Pub Med] 27. Ghabrial R, Quivey JM, Dunn JP Jr, Char DH. Radiation therapy of acquired immunodeficiency syndrome-related Kaposi’s sarcoma of the eyelids and conjunctiva. Arch Ophthalmol 1992;110:1423-6. [Pub Med] 28. Gonzales CA, Scott IU, Chaudhry NA, Luu KM, Miller D, Murray TG, Davis JL. Endogenous endophthalmitis caused by Histoplasma capsulatum var. capsulatum; a case report and literature review. Ophthalmology 2000;107:725-9. [Pub Med] 29. Hatton MP, Duker JS, Reichel E, Morley MG, Puliafito CA. Treatment of relapsed cytomegalovirus retinitis with the sustained-release ganciclovir implant. Retina 1998;18:50-5. [Pub Med] 30. Hicks CB, Benson PM, Lupton GP, Tramont EC. Seronegative secondary syphilis in a patient infected with the human immunodeficiency virus (HIV) with Kaposi sarcoma; a diagnostic dilemma. Ann Intern Med 1987;107:492-5; erratum p. 946. [Pub Med] 31. Hodge WG, Margolis TP. Herpes simplex virus keratitis among patients who are positive or negative for human immunodeficiency virus; an epidemiology study. Ophthalmology 1997;104:120-4. [Pub Med] 32. Holland GN, Engstrom RE Jr, Glasgow BJ, Berger BB, Daniels SA, Sidikaro Y, Harmon JA, Fischer DH, Boyer DS, Rao NA, Eagle RC Jr, Kreiger AE, Foos RY. Ocular toxoplasmosis in patients with the acquired immunodeficiency syndrome. Am J Ophthalmol 1988;106:653-67. [Pub Med] 33. Holland GN. Immune recovery uveitis. Ocular Immunol Inflamm 1999;7:215-21. [Pub Med] 34. Holland GN, Pepose JS, Pettit TH, Gottlieb MS, Yee RD, Foos RY. Acquired immune deficiency syndrome; ocular manifestations. Ophthalmology 1983;90:859-72; discussion by DS Boyer, 872-3. [Pub Med] 35. Hummer J, Gass JD, Huang AJ. Conjunctival Kaposi’s sarcoma treated with interferon alpha-2a. (letter) Am J Ophthalmol 1993;116:502-3. [Pub Med] 36. Jabs DA, Martin BK, Forman MS, Ricks MO for the Cytomegalovirus Retinitis and Viral Resistance Research Group. Cytomegalovirus (CMV) blood DNA load, CMV retinitis progression, and occurrence of resistant CMV in patients with CMV retinitis. J Infect Dis 2005; 192: 640 -9. [Pub Med] 37. Jabs DA, Van Natta ML, Thorne JE, Weinberg DV, Meredith TA, Kupperman BD, Sepkowitz K, Li HK, Studies of Ocular Complications of AIDS Research Group. Course of cytomegalovirus retinitis in the era of highly active antiretroviral therapy: Retinitis progression. Ophthalmology 2004;111:2224-31. [Pub Med] 38. Jabs DA, Van Natta ML, Thorne JE, Weinberg DV, Meredith TA, Kupperman BD, Sepkowitz K, Li HK, Studies of Ocular Complications of AIDS Research Group. Course of cytomegalovirus retinitis in the era of highly active antiretroviral therapy: Second eye involvement and retinal detachment. Ophthalmology 2004;111:2232-9.[Pub Med] 39. Jacobs DS, Piliero PJ, Kuperwaser MG, Smith JA, Harris SD, Flanigan TP, Goldberg JH, Ives DV. Acute uveitis associated with rifabutin use in patients with human immunodeficiency virus infection. Am J Ophthalmol 1994;118:716-22. [Pub Med] 40. Jones MR, Cunningham ET Jr. Bartonella henselae-associated acute multifocal retinitis in a patient with acquired immunodeficiency syndrome. Retina 1997;17:457-9. [Pub Med] 41. Kaimbo Wa Kaimbo D, Parys-Van Ginderdeuren R, Missotten L. Conjunctival squamous cell carcinoma and intraepithelial neoplasia in AIDS patients in Congo Kinshasa. Bull Soc Belge Ophtalmol 1998;268:135-41. [Pub Med] 42. Katlama C, Mouthon B, Gourdon D, Lapierre D, Rousseau F. Atovaquone as long-term suppressive therapy for toxoplasmic encephalitis in patients with AIDS and multiple drug intolerance; Atovaquone Expanded Access Group. AIDS 1996;10:1107-12. [Pub Med] 43. Karavellas MP, Lowder CY, Macdonald C, Avila CP Jr, Freeman WR. Immune recovery vitritis associated with inactive cytomegalovirus retinitis; a new syndrome. Arch Ophthalmol 1998;116:169-75. [Pub Med] 44. Karp CL, Moore JK, Rosa RH Jr. Treatment of conjunctival and corneal intraepithelial neoplasia with topical interferon α-2b. Ophthalmology 2001;108:1093-8. [Pub Med] 45. Karp CL, Scott IU, Chang TS, Pflugfelder SC. Conjunctival intraepithelial neoplasia; a possible marker for human immunodeficiency virus infection? Arch Ophthalmol 1996;114:257-61. [Pub Med] 46. Kestelyn P, Taelman H, Bogaerts, Kagame A, Abdel Aziz M, Batungwanayo J, Stevens AM, Van de Perre P. Ophthalmic manifestations of infections with Cryptococcus neoformans in patients with the acquired immunodeficiency syndrome. Am J Ophthalmol 1993;116:721-7. [Pub Med] 47. Knox CM, Chandler D, Short GA, Margolis TP. Polymerase chain reaction-based assays of vitreous samples for the diagnosis of viral retinitis; use in diagnostic dilemmas. Ophthalmology 1998;105:37-45. [Pub Med] 48. Koser MW, Jampol LM, MacDonell K. Treatment of Pneumocystis carinii choroidopathy. Arch Ophthalmol 1990;108: 1214-5.[Pub Med] 49. Kuppermann BD, Petty JG, Richman DD, Mathews WC, Fullerton SC, Rickman LS, Freeman WR. Correlation between CD4+ counts and prevalence of cytomegalovirus retinitis and human immunodeficiency virus-related noninfectious retinal vasculopathy in patients with acquired immunodeficiency syndrome. Am J Ophthalmol 1993;115:575-82. [Pub Med] 50. Lafeuillade A, Aubert L, Chaffanjon P, Quilichini R. Optic neuritis associated with dideoxyinosine. Lancet 1991;337: 615-6. [Pub Med] 51. Liota E, Smith KJ, Buckley R, Menon P, Skelton H. Imiquimod therapy for molluscum contagiosum. J Cutan Med Surg 2000;4:76-82. [Pub Med] 52. Luu KK, Scott IU, Chaudhry NA, Verm A, Davis JL. Intravitreal antiviral injections as adjunctive therapy in the managemtn of immunocompetent patients with necrotizing herpetic retinopathy. Am J Ophthalmol 2000; 29:811-3. [Pub Med] 53. Macdonald JC, Torriani FJ, Morse LS, Karavellas MP, Reed JB, Freeman WR. Lack of reactivation of cytomegalovirus (CMV) retintis after stopping CMV maintenance therapy in AIDS patients with sustained elevations in CD4 T cells in response to highly active antiretroviral therapy. J Infect Dis 1998;177:1182-7. [Pub Med] 54. Mansour AM. Orbital findings in acquired immunodeficiency syndrome. (letter) Am J Ophthamol 1990;110:706-7. [Pub Med] 55. Martin DF, Kuppermann BD, Wolitz RA, Palestine AG, Li H, Robinson CA. Oral ganciclovir for patients with cytomegalovirus retinitis treated with a ganciclovir implant; Roche Ganciclovir Study. N Engl J Med 1999;340:1063-70. [Pub Med] 56. McCann JD, Margolis TP, Wong MG, Kuppermann BD, Luckie AP, Schwartz DM, Irvine AR, Ai E. A sensitive and specific polymerase chain reaction-based assay for the diagnosis of cytomegalovirus retinitis. Am J Ophthalmol 1995;120: 219-26. [Pub Med] 57. McCluskey PJ, Goonan PV, Marriott DJ, Field AS. Microsporidial keratoconjunctivitis in AIDS. Eye 1993;7:80-3. [Pub Med] 58. Muccioli C, Belfort R Jr. Presumed ocular and central nervous system tuberculosis in a patient with the acquired immunodeficiency syndrome. Am J Ophthalmol 1996;121:217-9. [Pub Med] 59. Musch DC, Martin DF, Gordon JF, Davis MD, Kuppermann BD. Treatment of cytomegalovirus retinitis with a sustained-release ganciclovir implant; The Ganciclovir Implant Study Group. N Engl J Med 1997;337:83-90. [Pub Med] 60. Nanda M, Pflugfelder SC, Holland S. Fulminant pseudomonal keratitis and scleritis in human immunodeficiency virus-infected patients. Arch Ophthalmol 1991;109:503-5. [Pub Med] 61. Nguyen N, Rimmer S, Katz B. Slowed saccades in the acquired immunodeficiency syndrome. Am J Ophthalmol 1989; 107:356-60. [Pub Med] 62. Ormerod LD, Rhodes RH, Gross SA, Crane LR, Houchin KW. Ophthalmologic manifestations of acquired immune deficiency syndrome-associated progressive multifocal leukoencephalopathy. Ophthalmology 1996;103:899-906. [Pub Med] 63. Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection; HIV Outpatient Study Investigators. N Engl J Med 1998;338:853-60. [Pub Med] 64. Perez Blazquez E, Montero Rodriguez M, Mendez Ramos MJ. Tuberculous choroiditis and acquired immunodeficiency syndrome. Ann Ophthalmol 1994;26:50-4. [Pub Med] 65. Perry CM, Balfour JA. Fomivirsen. Drugs 1999;57:375-80; discussion 381. [Pub Med] 66. Rao NA, Zimmerman PL, Boyer D, Biswas J, Causey D, Beniz J, Nichols PW. A clinical, histopathologic, and electron microscopic studay of Pneumocystis carinii choroiditis. Am J Ophthalmol 1989;107:218-28. [Pub Med] 67. Reed JB, Scales DK, Wong MT, Lattuada CP Jr, Dolan MJ, Schwab IR. Bartonella henselae neuroretinitis in cat scratch disease; diagnosis, management, and sequelae. Ophthalmology 1998;105:459-66. [Pub Med] 68. Rivero ME, Kuppermann BD, Wiley CA, Garcia CR, Smith MD, Dreilinger A, Freeman WR. Acquired immunodeficiency syndrome-related intraocular B-cell lymphoma. Arch Ophthalmol 1999;117:616-22. [Pub Med] 69. Robinson MR, Udell IJ, Garber PF, Perry HD, Streeten BW. Molluscum contagiosum of the eyelids in patients with acquired immune deficiency syndrome. Ophthalmology 1992;99:1745-47. [Pub Med] 70. Rosenberg PR, Uliss AE, Friedland GH, Harris CA, Butkus Small C, Klein RS. Acquired immunodeficiency syndrome; ophthalmic manifestations in ambulatory patients. Ophthalmology 1983;90:874-8. [Pub Med] 71. Roth DB, Feuer WJ, Blenke AJ, Davis JL. Treatment of recurrent cytomegalovirus retinitis with the ganciclovir implant. Am J Ophthalmol 1999;127:276-82. [Pub Med] 72. Saran BR. Rifabutin-associated uveitis. Ann Pharmacother 1997;31:1405. [Pub Med] 73. Saran BR, Maguire AM, Nichols C, Frank I, Hertle RW, Brucker AJ, Goldman S, Brown M, Van Uitert B. Hypopyon uveitis in patients with acquired immunodeficiency syndrome treated for systemic Mycobacterium avium complex infection with rifabutin. Arch Ophthalmol 1994;112:1159- 65. [Pub Med] 74. Seiff SR, Margolis T, Graham SH, O’Donnell JJ. Use of intravenous acyclovir for treatment of herpes zoster ophthalmicus in patients at risk for AIDS. Ann Ophthalmol 1988;20:480-2. [Pub Med] 75. Sellitti TP, Huang AJ, Schiffman J, Davis JL. Association of herpes zoster ophthalmicus with acquired immunodeficiency syndrome and acute retinal necrosis. Am J Ophthalmol 1993;116:297- 301. [Pub Med] 76. Sha BE, Benson CA, Deutsch T, Noskin GA, Murphy RL, Pottage JC Jr, Finn WG, Roth SI, Kessler HA. Pneumocystis carinii choroiditis in patients with AIDS: clinical features, response to therapy, and outcome. J Acquired Immun Defic Syndr 1992:5;1051-8. [Pub Med] 77. Silverstein BE. Parasitic corneal infections. Int Ophthalmol Clin 1998;38:179-82. [Pub Med] 78. Spaide RF, Martin DF, Teich SA, Katz A, Toth I. Successful treatment of progressive outer retinal necrosis syndrome. Retina 1996;16:479-87. [Pub Med] 79. Stern JJ, Hartman BJ, Sharkey P, Rowland V, Squires KE, Murray HW, Graybill JR. Oral fluconazole therapy for patients with acquired immunodeficiency syndrome and cryptococcosis: experience with 22 patients. Am J Med 1988;85: 477-80. [Pub Med] 80. Studies of the Ocular Complications of AIDS Research Group in Collaboration with AIDS Clinical Trials Group. Combination foscarnet and ganciclovir therapy vs monotherapy for the treatment of relapsed cytomegalovirus retinitis in patients with AIDS; The Cytomegalovirus Retreatment Trial. Arch Ophthalmol 1996;114:23-33. [Pub Med] 81. Studies of Ocular Complications of AIDS Research group in Collaboration with the AIDS Clinical Trials Group. Foscarnet-ganciclovir cytomegalovirus retinitis trial. 4. Visual outcomes. Ophthalmology 1994;101:1250-61. [Pub Med] 82. Studies of Ocular Complications of AIDS (SOCA) Research Group in collaboration with the AIDS Clinical Trials Group (ACTG). Rhegmatogenous retinal detachment in patients with cytomegalovirus retinitis: the Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial. Am J Ophthalmol 1997;124:61-70. [Pub Med] 83. Thompson WS, Culbertson WW, Smiddy WE, Robertson JE, Rosenbaum JT. Acute retinal necrosis caused by reactivation of herpes simplex virus type 2. Am J Ophthalmol 1994;118:205-11. [Pub Med] 84. Tseng AL, Walmsley SL. Rifabutin-associated uveitis. Ann Pharmacother 1995;29:1149-55. [Pub Med] 85. Turok DI, Meyer DR. Orbital lymphoma associated with acquired immunodeficiency syndrome. Arch Ophthalmol 1992;110:610-1. [Pub Med] 86. Vann RR, Karp CL. Perilesional and topical interferon alfa-2b for conjunctival and corneal neoplasia. Ophthalmology 1999;106:91-7. [Pub Med] 87. Vitale AT, Spaide RF, Warren FA, Moussouris HF, D’Amico RA. Orbital aspergillosis in an immunocompromised host. (letter) Am J Ophthalmol 1992;113:725-6. [Pub Med] 88. Young S, Morlet N, Besen G, Wiley CA, Jones P, Gold J, Li Y, Freeman WR, Coroneo MT. High- dose (2000-μg) intravitreous ganciclovir in the treatment of cytomegalovirus retinitis. Ophthalmology 1998;105:1404-10. [Pub Med] 89. Zabawski EJ Jr. A review of topical and intralesional cidofovir. Derm On-Line J 2000;6:3. (http:/dermatology.cdlib.org) [Pub Med] 90. Zegans ME, Walton RC, Holland GN, O’Donnell JJ, Jacobson MA, Margolis TP. Transient vitreous inflammatory reactions associated with combination antiretroviral therapy in patients with AIDS and cytomegalovirus retinitis. Am J Ophthalmol 1998;125:292-300. [Pub Med]
|
|