eMedicine Specialties > Ophthalmology > Ophthalmology for the General Practitioner

Ocular Manifestations of HIV: Treatment & Medication

Author: Robert Copeland, MD, Chair, Associate Professor, Department of Ophthalmology, Howard University College of Medicine
Coauthor(s): Brian A Phillpotts, MD, Former Vitreo-Retinal Service Director, Former Program Director, Clinical Assistant Professor, Department of Ophthalmology, Howard University College of Medicine
Contributor Information and Disclosures

Updated: Oct 1, 2009

Treatment

Medical Care

• Herpes zoster ophthalmicus
  • Intravenous acyclovir 10 mg/kg 3 times per day for 7 days, followed by oral acyclovir 800 mg to 1 g 3-5 times per day for an additional 7 days. This regimen is most effective when started within 72 hours of onset of the vesicular lesions. This treatment reduces the frequency of recurrences. Oral acyclovir used in the treatment of HZO has been demonstrated in a randomized clinical trial to reduce the shedding of the virus from the vesicles, decrease systemic spreading of the virus, and reduce the severity and duration of HZO complications (eg, dendritic keratitis, stromal keratitis, uveitis). However, oral acyclovir does not affect the incidence, severity, or duration of postherpetic neuralgia.
  • Famciclovir 500 mg 3 times per day for 7 days. This has an advantage of causing less adverse effects. If unresponsive to acyclovir or famciclovir, intravenous foscarnet should be tried.
  • Topical antiviral agents have not been shown to be effective for the management of HZO.
  • If intraocular inflammation is present, topical cycloplegic agent (ie, scopolamine 0.25% tid) and a topical steroid (ie, prednisolone acetate 1% q1-2h) should be started.
  • Generally, it is recommended that oral steroids be avoided because of the risk of further immunosuppression of the patient and exacerbation of the infection. However, oral steroids have been used by dermatology for the treatment of HZO to reduce the incidence of postherpetic neuralgia in patients older than 60 years.
  • Alternatively, topical capsaicin 0.25% ointment applied to the involved skin twice daily, or amitriptyline 25 mg by mouth 3 times daily may be useful in reducing the symptoms of postherpetic neuralgia.
  • In case of persistent punctate keratopathy, copious, nonpreserved ocular lubricant ointments, bandage contact lenses, or tarsorrhaphy may be needed.
• Kaposi sarcoma
  • Radiation therapy is effective for eyelid and conjunctival Kaposi sarcoma. Adverse effects of radiation therapy include loss of lashes, skin irritation, and conjunctivitis.
  • Local cryotherapy of eyelid and conjunctival lesions may be performed.
  • Intralesional chemotherapy with vinblastine, alpha interferon, and liposomal daunorubicin may be administered.
  • Surgical excision of the tumor may be performed in some patients with severe symptoms.
• Conjunctival microvasculopathy - Observation
• Keratoconjunctivitis sicca - Artificial tears and long-acting lubricating ointments used in association with punctal plugs for symptomatic relief.
• Molluscum contagiosum lesions of the skin can be treated with incision with or without curettage, cryotherapy, or various topical agents, including phenol and trichloracetic acid. Surgical treatment, although useful for individual lesions, may be inappropriate for patients with multiple lesions of the eyelids. Reconstitution of immune function with HAART can result in resolution of molluscum contagiosum without therapy directed toward the virus, but clearing of cutaneous lesions can take 5-6 months after the initiation of therapy.
• Varicella-zoster virus keratitis
  • Oral acyclovir 800 mg 5 times per day or famciclovir 125-500 mg by mouth 3-5 times per day. Chronic treatment may be required for VZV keratitis. This usually minimizes symptoms and shortens the duration of viral shedding.
  • Severe disciform stromal keratitis that causes significant reduction in visual acuity may be treated with topical corticosteroids.
• Herpes simplex virus keratitis
  • Most cases of HSV epithelial keratitis resolve spontaneously within several weeks. The rationale for treatment is to decrease corneal damage due to lytic viral infection and virus-incited immunologic response. Debridement of HSV epithelial keratitis with a dry cotton-tipped applicator or a cellulose sponge can hasten resolution and decrease the load of infectious virus and viral antigens.
  • Medical treatment includes the use of vidarabine ophthalmic 3% ointment 5 times daily for 14 days and/or trifluridine ophthalmic 1% solution every 3 hours for 14 days; or acyclovir topical 3% ointment 5 times daily for 14 days or oral dosage form 400 mg 5 times daily for 7 days; or famciclovir 500 mg by mouth 3 times daily for 7 days.
  • HSV neurotrophic keratopathy is a condition that should be managed with nonpreserved lubricants, eyelid patching, bandage contact lenses, and sometimes autologous serum and nerve growth factor.
• Fungal keratitis - Initially, corneal infiltrates and ulcers usually are treated as bacterial infections until the results of cultures and/or staining are obtained. If cultures indicate fungal keratitis, then the following action is recommended:
  • Patient should be admitted, unless very reliable, and start natamycin 5% (50 mg/mL) drops every 1-2 hours while awake and every 2 hours during the night hours.
  • Use a cycloplegic agent (eg, homatropine 5% tid, scopolamine 0.25% tid).
  • Avoid topical steroids.
  • Avoid eye patching.
  • For deep stromal infection, combination medication is recommended; topical amphotericin B, topical fumagillin, miconazole or clotrimazole and/or oral fluconazole, itraconazole, or albendazole.
• Microsporidia - Topical fumagillin has been used successfully to treat keratoconjunctivitis secondary to Microsporidia.
• Iridocyclitis - Topical corticosteroid drops are used frequently but with extreme caution and with proper antimicrobial coverage when infection is suspected. If toxicity from the medication is suspected, the dose should be tapered or the causative agent should be discontinued.
• HIV retinopathy - No treatment is required.
• Cytomegalovirus retinitis
  • Specific agents and modalities for the treatment of CMV retinitis include the following: oralvalganciclovir; oral, intravenous, and intravitreal ganciclovir; intravenous and intravitreal foscarnet or combined intravenous ganciclovir and foscarnet; or intravenous cidofovir. These agents, ganciclovir, foscarnet, and cidofovir, act by inhibiting CMV DNA polymerase.
  • Valganciclovir is the drug of choice for the treatment of CMV retinitis because of its convenience, lower cost, and lack of complications associated with IV administration. Valganciclovir is the valine ester of ganciclovir. The addition of the valine moiety increases the absorption of ganciclovir 10-fold. It is available as a 450-mg tablet. The recommended dose for induction is 900 mg twice a day and then 900 mg once a day for maintenance. Adverse effects are similar to those of intravenous ganciclovir and require periodic monitoring of complete blood count and renal function. Given the need for lifelong therapy for CMV retinitis in some HIV-positive patients, valganciclovir is a welcome alternative to long-term administration of intravenous antivirals.
  • Ganciclovir - Start induction with 5 mg/kg IV q12h for 14 days, then change to a maintenance IV dose of 5 mg/kg/d for 7 days. Adjust dose accordingly with renal insufficiency. The significant adverse effect with ganciclovir is myelosuppression. Monitor CBC with differential 2-3 times a week during induction phase, and weekly thereafter. If absolute neutrophil count drops less than 500 or platelet count drops less than 10,000, discontinue ganciclovir treatment.
  • During the treatment of CMV retinitis with ganciclovir, the dose of zidovudine may need to be reduced, unless hematopoietic growth factors (eg, regramostim, filgrastim) are used concurrently. This prevents exacerbation of myelosuppression.
  • Alternatively, intravitreal ganciclovir may be implanted to ensure adequate and prolonged intravitreal concentration of the drug. However, this does not preclude the use of oral ganciclovir to control the systemic infection.
  • Foscarnet - Start induction with 60 mg/kg IV q8h for 14 days, then change to a maintenance IV dose of 90-120 mg/kg/d. Hydration with 1000 mL of isotonic sodium chloride solution is recommended due to renal toxicity of foscarnet. Therefore, it is recommended that electrolyte status, particularly calcium and magnesium, serum creatine, and hemoglobin be monitored 2-3 times per week for 2 weeks, and weekly thereafter. Dosage adjustment is recommended if renal insufficiency is present, and the drug should be discontinued if serum creatine is greater than 2.8 mg/dL.
  • Cidofovir - Start induction with 5 mg/kg IV over 1 hour once weekly for 2 weeks, then change to maintenance dose of 5 mg/kg over 1 hour once every other week. This drug is nephrotoxic. Concurrent use of probenecid with cidofovir and hydration with 1-2 liters of normal saline reduces the risk of renal toxicity. Other adverse effects of cidofovir include iritis and ocular hypotony.
• Acute retinal necrosis
  • Start acyclovir 5-10 mg/kg/d IV in 3 divided doses for 1 week, then change to oral acyclovir 800 mg 5 times daily for the following 1-2 months. Monitor blood urea nitrogen and creatine levels because of the nephrotoxic effect of acyclovir.
  • Start a slow tapering dosage of prednisone 60-100 mg PO daily 24 hours after starting acyclovir, continue for about 1-2 months. Be sure to obtain a chest x-ray and PPD before starting the oral steroid.
  • A topical steroid, such as prednisolone acetate 1%, instilled q2-6h, and a cycloplegic agent, such as homatropine 5% instilled 2-3 times daily.
  • Add Zantac 150 mg PO twice daily for steroid-induced gastritis.
  • In fulminate cases, particularly in HIV-positive patients, IV or intravitreal ganciclovir and/or foscarnet, or intravenous cidofovir may be considered (see CMV for dosage).
  • Use of retinal laser photocoagulation to surround the necrotic lesion is still controversial.
  • For retinal detachment, vitrectomy, membranectomy, endolaser, and silicone oil infusion usually is required.
• Progressive outer retinal necrosis - See ARN for the treatment of VZV-associated retinitis in HIV patients.
• Syphilis
  • All HIV-positive patients with syphilitic eye findings are considered to have tertiary syphilis and are treated accordingly.
  • Treatment of syphilis is with intravenous penicillin G (24 million U/d for 7-10 d). Relapse may occur in spite of adequate treatment. For penicillin-allergic patients, tetracycline 500 mg 4 times per day or doxycycline 200 mg twice a day by mouth for 30 days or a third-generation cephalosporin (ceftriaxone).
  • Cycloplegia with either cyclopentolate 2% or homatropine 5% 3 tid and prednisolone acetate 1% qid is recommended if anterior segment inflammation is present.
• Tuberculosis
  • Patients should be given isoniazid (INH) 300 mg PO daily, rifampin 600 mg PO daily, and pyrazinamide 25-35 mg/kg PO daily for 2 months; then, continue with INH and rifampin for an additional 7 months. Drug resistance is most common with streptomycin and INH; however, this may be minimized by the use of multiple bacteriocidal antituberculous drugs.
  • Pyridoxine 25 mg PO daily usually is added to the regimen to prevent peripheral neuritis.
• P carinii is treated with intravenous Bactrim (trimethoprim/sulfamethoxazole) or intravenous pentamidine.
• Toxoplasma retinochoroiditis
  • For small peripheral retinochoroiditis (not affecting or threatening the macula) - Treat anterior chamber inflammation with a topical cycloplegic with or without topical steroid (eg, prednisolone acetate 1% qid). The topical steroid should be tapered gradually as the anterior chamber inflammation resolves.
  • For active retinochoroiditis within 2-3 mm of the disc or fovea, which threatens vision, or peripheral lesion associated with severe vitritis - Start first-line therapy for 3-6 weeks, as follows: (1) pyrimethamine 75 mg PO load, 25 mg PO bid, plus, (2) folinic acid 3-5 mg PO twice weekly (to reduce the adverse effect of bone marrow toxicity of pyrimethamine), and (3) sulfadiazine 2 g PO load, then 1 g PO qid.
  • Clindamycin 300 mg PO qid may be used with sulfadiazine as alternative treatment. Patients on clindamycin should be monitored for the possible adverse effect of pseudomembranous colitis. Other alternative therapeutic regimens include the following: trimethoprim/sulfamethoxazole (160 mg/800 mg) 1 tablet PO bid, with or without clindamycin.
  • Platelet count and CBC should be monitored once to twice weekly for patients on pyrimethamine. If the platelet count falls below 100,000, then a reduction in the dose along with an increase in the dose of folinic acid should be initiated. It is important that patients on pyrimethamine avoid taking vitamins containing folic acid.
  • Retinal laser photocoagulation, cryotherapy, and vitrectomy have been used as adjunct therapy in the treatment of ocular toxoplasmosis.
• Histoplasma chorioretinitis
  • Following diagnosis of disseminated histoplasmosis, amphotericin, or ketoconazole is the recommended pharmacologic treatment of choice. Patients with AIDS usually receive a higher dose of amphotericin B (1-2.5 g), followed by daily ketoconazole (lifelong), or weekly maintenance amphotericin B treatment.
  • Laser retinal photocoagulation may be used to treat CNVM in the macula.
  • Treatment is recommended within 72 hours of the diagnosis of CNVM with positive fluorescein angiography.
  • Amsler grid use daily is recommended to assess central vision, and patients are advised to report any sudden change in vision as soon as possible.
• Cryptococcal chorioretinitis
  • Early diagnosis and treatment of cryptococcal chorioretinitis is important. Combination treatment with flucytosine and intravenous amphotericin B is considered the treatment of choice for disseminated or meningeal cryptococcal infection. However, there have been cases of cryptococcal chorioretinitis successfully treated with intravenous amphotericin B alone.
  • Fluconazole and itraconazole have been reported to be effective in the treatment of cryptococcal chorioretinitis.
  • Early vitrectomy is recommended with persistent vitritis despite treatment.
• Options for neuro-ophthalmologic manifestations in HIV include radiation for lymphoma and specific antibiotics for infectious causes. No treatment is available for progressive multifocal leukoencephalopathy (PML).

Consultations

Consultation with an internist for proper monitoring and treatment of the HIV infection is recommended.

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Antivirals

Reduce frequency of recurrence. In HZO, oral acyclovir has been reported to reduce shedding of virus from vesicles, decrease systemic spreading of virus, and reduce severity and duration of HZO complications (eg, dendritic keratitis, stromal keratitis, uveitis). However, oral acyclovir does not affect incidence, severity, or duration of postherpetic neuralgia. Topical antiviral agents have not been shown to be effective for the management of HZO.

Cidofovir (Vistide)

For CMV retinitis, nucleotide analog that selectively inhibits viral DNA production in CMV and other herpes viruses.

Acyclovir (Zovirax)

Indicated for initial and recurrent treatment of oral and genital herpes (HSV-1 and HSV-2), particularly in immunocompromised patients. Indicated also for treatment of herpes zoster (shingles) and chickenpox.

Famciclovir (Famvir)

Prodrug of antiviral agent penciclovir, which inhibits DNA synthesis in HSV types 1 and 2, as well as VZV. Indicated for treatment of HZV infection. Has the advantage of causing less adverse effects.

Vidarabine (Vira-A)

For keratoconjunctivitis. Topical idoxuridine that interferes with early steps of viral DNA synthesis. If no signs of improvement after 7 d or incomplete reepithelialization in 21 d, consider alternative therapy. Severe cases may require longer treatment. After reepithelialization occurs, treat bid for another 7 d to prevent recurrence.

Trifluridine (Viroptic)

For herpes simplex infections. Inhibits viral replication by incorporating into viral DNA in place of thymidine. If no response in 7-14 d, consider other treatments.

Foscarnet (Foscavir)

Use in CMV retinitis in individuals with AIDS. Foscarnet is a pyrophosphate analogue, which acts as a noncompetitive inhibitor of several RNA and DNA polymerases, and HIV reverse transcriptase. It is a virostatic, and does not require activation by thymidine kinase for activity.

Ganciclovir (Cytovene)

Used in the treatment of CMV retinitis in immunocompromised patients, including patients with AIDS; prophylaxis of CMV infection in transplant patients; may be used in combination with foscarnet in patients who relapse after monotherapy with either drug.

Valganciclovir (Valcyte)

L-valyl ester prodrug of ganciclovir used to treat cytomegalovirus (CMV) retinitis in patients with AIDS. Ganciclovir is synthetic analogue of 2'-deoxyguanosine, which inhibits replication of human CMV in vitro and in vivo. Inhibits viral activity by inhibiting viral DNA synthesis. bioavailability of valganciclovir is significantly higher than from ganciclovir capsules. Has the advantage of qd or bid PO administration. Achieves levels comparable to those obtained with IV ganciclovir.
Indicated for the treatment of CMV retinitis in patients with AIDS. Valcyte tablets are administered orally and should be taken with food. If renal function is impaired, dosage adjustments are required for valganciclovir.

Amitriptyline (Elavil)

For depressions, herpetic neuralgic pain. Inhibits reuptake of serotonin and/or norepinephrine at presynaptic neuronal membrane, which increases concentration in CNS.

Mydriatics/cycloplegics

Reduce pain from ciliary muscle spasm that is seen with uveitis. Formation of posterior synechiae from intraocular inflammation also is prevented.

Cyclopentolate HCl (Cyclogyl)

Anticholinergic whose action blocks cholinergic stimulation of iris sphincter muscle and ciliary body producing pupillary dilation and paralysis of accommodation.

Scopolamine HBr 0.25% (Isopto Hyoscine)

Anticholinergic agent that inhibits cholinergic stimulation of iris sphincter muscle and ciliary body thus causing pupillary dilation and paralysis of accommodation.
Indicated for mydriasis and cycloplegia in diagnostic procedures and in therapy of iridocyclitis.

Antifungals

Their mechanism of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.

Amphotericin B (Amphocin; Fungizone)

For fungal infections. Polyene antibiotic produced by a strain of Streptomyces nodosus; can be fungistatic or fungicidal. Binds to sterols, such as ergosterol, in the fungal cell membrane, causing intracellular components to leak with subsequent fungal cell death.

Flucytosine (Ancobon)

For fungal infections. Converted to fluorouracil after penetrating fungal cells. Inhibits RNA and protein synthesis. Active against Candida and Cryptococcus species and generally used in combination with amphotericin B.

Fluconazole (Diflucan)

For fungal infections. Fungistatic activity. Synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes.

Itraconazole (Sporanox)

For candidiasis. Fungistatic activity. Synthetic triazole antifungal agent that slows fungal cell growth by inhibiting cytochrome P-450-dependent synthesis of ergosterol, a vital component of fungal cell membranes.

Albendazole (Albenza)

For hookworm, pinworm, roundworm. Decreases ATP production in worm, causing energy depletion, immobilization, and finally death.

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