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Ocular Complications in HIV Patients
Lucia Sobrin, M.D., Janet L. Davis, M.D.
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.
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).
DIFFERENTIAL DIAGNOSIS
Subjective Complaints Blurred Vision
Eye Pain
Double Vision
Visual Field Defects
Visible Lesions of the Adnexae and External Eye
Inflammation of Anterior Segment (Iritis)
Retina and Choroid
Neuro-ophthalmic
Orbital
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.
CLINICAL MANIFESTATIONS Signs and Symptoms Subjective 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. 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. Kaposi Sarcoma Lesions: 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. Herpes Zoster Ophthalmicus: 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. 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. 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. 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. 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). 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. 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. 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. 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. 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. Retina and Choroid: Posterior segment disease can be divided into three categories: vascular, infectious, and neoplastic. 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. Diabetic Retinopathy: in HIV patients with preexisting diabetes appears to be more severe and rapidly progressive, presumably from cumulative damage to the vascular beds. 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. 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. 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. 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. 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. 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. 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). 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). 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. 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. 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). 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). 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). Orbital 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. 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).
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.
DIAGNOSIS 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. 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. 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. 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. 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. 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. 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. Invasive Diagnostic Tests 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. 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. 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. 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. 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).
MANAGEMENT Table 1 summarizes drug therapies for various HIV ocular complications. 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). 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). Retina and Choroid Treatment for HIV retinopathy is immune reconstitution via HAART. 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. 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. 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). 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. 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. 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. 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. 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. 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). 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. 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. 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). 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. 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). 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. 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).
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
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]
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