eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Chorioretinitis: Treatment & Medication

Author: Ayesha Mirza, MD, Assistant Professor, Pediatric Infectious Diseases, University of Florida College of Medicine Jacksonville
Coauthor(s): Diana E Guinazu, MD, Fellow in Pediatric Infectious Diseases, University of Florida College of Medicine
Contributor Information and Disclosures

Updated: Oct 16, 2009

Treatment

Medical Care

• Medical care in chorioretinitis (CR) focuses on the establishment of specific therapies for treatable etiologies and on the stabilization of the patient with chorioretinitis to prevent further loss of vision especially in immunocompromised infants and children.
• Care for individuals with chorioretinitis is complex and requires thorough consideration of short-term and long-term care and goals to maintain quality of life.
• Available treatment options for specific causes of chorioretinitis are as follows:
  • Antivirals: Four drugs have been licensed for the systemic treatment of cytomegalovirus (CMV) infection. These include ganciclovir, valganciclovir (oral prodrug of ganciclovir), foscarnet, and cidofovir. Fomivirsen is licensed for intravitreal administration to treat CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS). Newer drugs such as maribavir, which has the potential to be useful in ganciclovir-resistant strains of CMV, are under clinical investigation.^8,23
  • For children with human immunodeficiency virus (HIV) infection, the drug of choice for initial treatment for CMV retinitis is intravenous ganciclovir. Oral valganciclovir is an option primarily for older children who are able to receive the adult dose and tablet formulation of valganciclovir. An alternative to treat CMV disease or for use in ganciclovir-resistant CMV infections in children with HIV is foscarnet. Combination therapy with ganciclovir and foscarnet delays progression of retinitis in certain patients failing monotherapy and can be used as initial therapy among children with sight-threatening disease. Intravenous ganciclovir and foscarnet may also be considered in initial therapy of CMV CNS disease. However, combination therapy is associated with substantial rates of adverse effects.
  • Several agents are used to treat toxoplasmosis. Treatment with antiparasitic drugs is effective for active infections but not for the encysted form. The classic treatment includes triple drug therapy with pyrimethamine (0.5-1 mg/kg/d), sulfadiazine (120-150 mg/kg/d), and prednisone. Concurrent folinic acid helps to minimize bone marrow toxicity produced by the pyrimethamine. High-performance liquid chromatography with ultraviolet and mass spectrometric detection has been developed for monitoring the plasma levels of pyrimethamine and sulfadiazine during treatment using a small amount of plasma (25 mcL). This may be helpful in determining the relationship between plasma concentrations and treatment efficacy.²⁴
  • Alternative antibiotic treatments include atovaquone (40 mg/kg/d has been used in adults, no dosage for children), azithromycin (5 mg/kg/d) and trimethoprim-sulfamethoxazole (40 mg/kg/d sulfamethoxazole, 8 mg/kg/d trimethoprim). Adjunctive clindamycin (20 mg/kg/d) is used for coverage against the encysted form. Treatment duration for congenital infection is typically 1 year.
  • Prevention of fetal infection after maternal Toxoplasma seroconversion during pregnancy is attempted with spiramycin administration. A 60% decrease has been reported in the congenital infection rate in patients who received this treatment; however, it does not ameliorate the fate of infants who are infected.
  • Catscratch disease is usually a self-limited disease in immunocompetent patients. B henselae is sensitive to many antibiotics in vitro, but only aminoglycosides have bactericidal activity. In immunocompetent patients, doxycycline at 200 mg/d is usually administered because of its property to cross the blood-brain and blood-ocular barrier. Caution should be used if administered to children because it may cause dental changes. Ciprofloxacin (1.5 g/d), gentamicin (3-5 mg/kg/d), erythromycin (20-50 mg divided into 3 doses; adults, 2 g/d), trimethoprim-sulfamethoxazole (40 mg/kg/d sulfamethoxazole, 8 mg/kg/d trimethoprim) are good alternatives and, like doxycycline, are usually given for 14-28 days. Immunodeficient patients need a more prolonged course of treatment, usually as long as 4 months. Steroids are also indicated for ocular disease.^25,26
  • Treatment of chorioretinitis due to fungal infections can be difficult and prolonged. Intravitreous amphotericin B (5-10 mcg) has been used to treat serious fungal chorioretinitis.
    • Candida species infection: Fluconazole (6-12 mg/kg/d) and amphotericin B (0.75-1 mg/kg/d) has been recommended as preferred antifungals for treatment of Candida endophthalmitis. New-generation triazoles (eg, voriconazole, posaconazole, ravuconazole) are changing the conventional approach to fluconazole-resistant Candida strains, as well as the approach to fungal endophthalmitis. Caspofungin is the first echinocandin approved to treat fungal endophthalmitis. Concomitant systemic caspofungin and voriconazole therapy has successfully treated endophthalmitis due to Candida albicans.^27,28,29,30 Experimental intraocular voriconazole (£ 25 mcg/mL) has been used for azole-resistant Candida infection with some success.
    • Ocular histoplasmosis: Treatment is limited to photocoagulation of neovascular membranes, particularly when the macula is threatened. Antifungal therapy has no role in treatment of this disease because no actively replicating organisms are present. Amphotericin B is used to treat systemic disease (0.75-1 mg/kg/d).³¹
    • Cryptococcus species infection: Amphotericin B (0.75-1 mg/kg/d) is used.
  • Antituberculosis drugs are administered in patients with M tuberculosis (MTB) and include isoniazid (10-30 mg/kg/d), rifampicin (10-20 mg/kg/d), pyrazinamide (30 mg/kg/d), and ethambutol (15 mg/kg/d). Other drugs, such as aminoglycosides and quinolones, may be used for treatment of drug-resistant organisms. Duration of therapy depends on the extent of the disease and on the immune status of the host.
  • Anthelmintics, including diethylcarbamazine (6 mg/kg/d), albendazole (400 mg PO bid), and mebendazole (100-200 mg PO bid), are usually administered with corticosteroids in patients with toxocariasis or baylisascariasis.
  • Etiologic treatments may not alter the clinical course of chorioretinitis because the pathologic changes may be due to an inflammatory and/or immunologic response instead of infection.
  • Treatment of other infectious etiologies, such as syphilis, yersiniosis, neuroborreliosis, depends on extent of disease but is likely to be successful in most patients.
• Eye symptoms can be treated as follows:
  • Steroids may have a role in the acute management of many vasculitides, collagen vascular diseases, or sarcoidosis; in some infectious processes (eg, MTB); or in some cases infections caused by Toxoplasma species.
  • Laser treatment of retinal lesions is used in certain conditions with good results.

Surgical Care

• Vitrectomy is usually not needed and is reserved for severe cases that are resistant to conservative medical treatment. 
• Ocular cytology used to detect the presence of eosinophils, ocular antibody, and immunoglobulin E (IgE) levels should always be performed to differentiate toxocaral ocular larva migrans from malignant retinoblastoma to prevent unnecessary enucleations.

Consultations

• Involvement of the following specialists is helpful in performing a diagnostic workup, determining the length of treatment, and planning the total management of a child with chorioretinitis:
  • Ophthalmologist - For determination of eye damage, treatment, and long-term follow-up care 
  • Infectious disease specialist - For diagnostic workup, selection of therapeutic agents and options, investigation of potential drug toxicities, and determination of treatment length in consultation with the ophthalmologist
• Other specialists include the following:
  • Neurologist - For seizure control and long-term follow-up care of neurologic deficits 
  • Allergy and immunology/rheumatology specialist - To treat other associated conditions (ie, juvenile rheumatoid arthritis)
  • Audiologist - For assessment and corrective measures to detect and treat deafness (if possible)
  • Physical therapist - For maximization of functions and range of motions of muscles and joints and for referral to an orthopedist for surgical intervention if needed
• Occasionally, genetic testing is required to investigate possible dysmorphic syndromes.

Medication

Over the last few years the list of therapeutic options available has grown. This section includes information on specific treatment options available.

Antivirals

Treatment of congenital viral infections with chorioretinitis, such as HSV (CNS, mucocutaneous, sepsis), CMV, or varicella-zoster virus, has resulted in lower mortality rates. Older children may benefit from intravitreal administration, which requires consultation with an ophthalmologist.

Foscarnet (Foscavir)

Analog of pyrophosphate. Inhibits DNA polymerase of CMV and reverse transcriptase of HIV. Virostatic with renal excretion. As effective as ganciclovir. Median time to relapse is 53 d.
In the foscarnet and ganciclovir CMV retinitis trial, 234 newly diagnosed patients were randomized. Same efficacy was reported for controlling retinitis and preserving vision. Survival with foscarnet was 12.6 mo versus 8.5 for ganciclovir group; mortality risk was 1.79x. Controlling for antiretroviral use, still better survival with foscarnet. Foscarnet has anti-HIV activity but has more dose-limiting toxicity.

Valganciclovir (Valcyte)

L-valyl ester prodrug of ganciclovir used to treat 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. Has the advantage of once daily or bid PO administration. Achieves levels comparable to those obtained with IV ganciclovir.

Acyclovir (Zovirax, Avirax)

Indicated for neonatal HSV and varicella-zoster infections. Treatment is most efficacious when started earlier in disease course. More effective in younger children than in adults.

Ganciclovir (Cytovene)

Indicated for CMV retinitis. Synthetic guanine derivative active against CMV. An acyclic nucleoside analog of 2'-deoxyguanosine that inhibits replication of herpes viruses both in vitro and in vivo. Levels of ganciclovir-triphosphate are as much as 100-fold more than in CMV-infected cells than in uninfected cells, possibly due to preferential phosphorylation of ganciclovir in virus-infected cells. For patients who experience progression of CMV retinitis while receiving a maintenance treatment with either dosage form of ganciclovir, the reinduction regimen should be administered.

Cidofovir (Vistide)

Used for CMV retinitis. Nucleotide analog that selectively inhibits viral DNA production in CMV and other herpes viruses.

Antitoxoplasmosis agents

Pyrimethamine and sulfadiazine are synergistic against Toxoplasma species. Spiramycin is used to treat pregnant women. Clindamycin has occasionally been administered to patients with AIDS and CNS toxoplasmosis. It is also used in patients who are unable to tolerate pyrimethamine and sulfadiazine due to side effects. Other treatments with atovaquone and newer macrolide antibiotics are being investigated.

Pyrimethamine (Daraprim)

Folic acid antagonist that selectively inhibits plasmodial dihydrofolate reductase. Highly selective against plasmodia and T gondii. Length of treatment is not well documented. Some infants with active chorioretinitis have been treated for more than 6 mo. Most often combined with sulfadiazine or clindamycin.

Sulfadiazine (Microsulfon)

Used synergistically with pyrimethamine. Length of treatment is not well documented. Some infants with active chorioretinitis have been treated for more than 6 mo. Administer with pyrimethamine.

Spiramycin

Used in European countries to lower risk of vertical transmission of toxoplasmosis in primoinfections of pregnant women by 60% but does not ameliorate fate of infants who are infected. Not commercially available in the US (obtain from FDA). Take on an empty stomach.

Clindamycin (Cleocin)

Lincosamide for treatment of serious skin and soft tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. As an alternative to sulfonamides, clindamycin may be beneficial when used with pyrimethamine in acute treatment of CNS toxoplasmosis in patients with AIDS.

Dapsone (Avlosulfon)

Bactericidal and bacteriostatic against mycobacteria; mechanism of action is similar to that of sulfonamides where competitive antagonists of PABA prevent formation of folic acid, inhibiting bacterial growth.

Antifungals

Amphotericin B and its various lipid forms are the principal drugs for parenteral use. For synergy, 5 flucytosine (5FC) could be administered with amphotericin B. Azoles (chiefly fluconazole, itraconazole, and voriconazole) are agents of choice for long-term oral therapy. Both voriconazole and caspofungin are being increasingly used in patients with susceptible fungal infections as well as those resistant to conventional antifungal agents

Amphotericin B (Amphocin, Fungizone)

Produced from a strain of Streptomyces nodosus. Antifungal activity of amphotericin B results from its ability to insert itself into fungal cytoplasmic membrane at sites containing ergosterol or other sterols. Aggregates of amphotericin B accumulate at sterol sites, resulting in an increase in cytoplasmic membrane permeability to monovalent ions (eg, potassium, sodium). At low concentrations, the main effect is increased intracellular loss of potassium, resulting in reversible fungistatic activity; however, at higher concentrations, pores of 40-105 nm in cytoplasmic membrane are produced, leading to large losses of ions and other molecules. A second effect of amphotericin B is its ability to cause auto-oxidation of the cytoplasmic membrane and release of lethal free radicals. Main fungicidal activity of amphotericin B may reside in ability to cause auto-oxidation of cell membranes.
Particularly active against Candida, Cryptococcus, and Aspergillus species.
Fungal endophthalmitis has been treated with intraocular injection of amphotericin B. An infectious diseases specialist should be consulted regarding the appropriate protocol and dosage. Several studies have shown poor intravitreal penetration when administered systemically.
Special attention is required when making the dilutions and injecting in gas-filled eyes because it has a narrow therapeutic range and can cause retinal toxicity. Subconjunctival injections of amphotericin B have no role in fungal ocular infections.

Flucytosine (Ancobon)

Although the exact mode of action is unknown, flucytosine is believed to act directly on fungal organisms by competitive inhibition of purine and pyrimidine uptake and is believed to act indirectly by intracellular metabolism, in which it is converted to 5-fluorouracil after penetrating fungal cells. Inhibits RNA and protein synthesis. Active against Candida and Cryptococcus species; generally used in combination with amphotericin B.
Use in combination with another agent because acquired resistance develops frequently when flucytosine is administered alone.
Well absorbed PO but should be administered IV to critically ill patients.

Fluconazole (Diflucan)

Synthetic PO 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. Has little affinity for mammalian cytochromes, which is believed to explain its low toxicity. Available as tablets for PO administration, as a powder for PO susp, and as a sterile solution for IV use. Has fewer adverse effects and better tissue distribution than older systemic imidazoles.
Effective against Candida, Cryptococcus, and Aspergillus species. Bioavailability following PO administration is comparable with parenteral administration. Good CSF and intravitreal penetration is achieved after systemic administration.

Itraconazole (Sporanox)

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.

Voriconazole (VFEND)

Used for primary treatment of invasive aspergillosis and treatment of Fusarium species or Scedosporium apiospermum infections. A triazole antifungal agent that inhibits fungal cytochrome P450-mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis. Has also proven to be effective for the treatment of disseminated Candida infections as well as other fungal infections (eg, cryptococcus, Blastomyces).

Caspofungin (Cancidas)

Used to treat refractory invasive aspergillosis. First of a new class of antifungal drugs (glucan synthesis inhibitors). Inhibits synthesis of beta-(1,3)-D-glucan, an essential component of fungal cell wall. Also approved for the treatment of candidemia and general invasive candidiasis in adult patients. Emerging role in treating fungal endophthalmitis with or without voriconazole.

Anthelmintics

Parasite biochemical pathways are different from those of the human host; thus, the toxicity is directed to the parasite, egg, or larvae. The mechanism of action varies within the drug class. Antiparasitic actions may include the following:

• Inhibition of microtubules, which causes irreversible block of glucose uptake
• Tubulin polymerization inhibition
• Depolarizing neuromuscular blockade
• Cholinesterase inhibition
• Increased cell membrane permeability, resulting in intracellular calcium loss
• Vacuolization of the schistosome tegument
• Increased cell membrane permeability to chloride ions via chloride channels alteration

Albendazole (Albenza)

A benzimidazole carbamate drug that inhibits tubulin polymerization, resulting in degeneration of cytoplasmic microtubules. Decreases ATP production in worms, causing energy depletion, immobilization, and, finally, death. Converted in the liver to its primary metabolite, albendazole sulfoxide. Less than 1% of the primary metabolite is excreted in the urine. Plasma level is noted to significantly rise (as much as 5-fold) when ingested after high-fat meal. Experience with patients <6 y is limited.
To avoid inflammatory response in CNS, patients must also be started on anticonvulsants and high-dose glucocorticoids.

Diethylcarbamazine (Hetrazan)

A piperazine derivative, diethylcarbamazine has effects on the 5-lipoxygenase pathway, targets the cyclooxygenase pathway and COX-1, and enhances the phagocytosis of the parasite.

Mebendazole (Vermox)

Exerts inhibitory effect on tubulin polymerization resulting in loss of cytoplasmic microtubules in the parasite.

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