eMedicine Specialties > Ophthalmology > Cornea
Keratitis, Interstitial: Treatment & Medication
Updated: Dec 14, 2007
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Treatment of IK is dependent on the specific underlying disorder.
- The use of topical corticosteroids has markedly changed the natural history of IK due to congenital syphilis. Without the use of these anti-inflammatory modifiers, the typical scenario was permanent corneal opacity with variable visual outcome. Due to its anti-inflammatory properties, topical corticosteroids reduce inflammation and neovascularization and often result in better visual acuity than if the condition were left untreated.
- Treatment of syphilitic IK includes antibiotic therapy for untreated cases. Intravenous penicillin is the preferred treatment, and the dosages vary depending on the stage of disease. Most commonly, tertiary syphilis or neurosyphilis dosages of intravenous penicillin are administered. Ocular therapy is concentrated on reducing the local inflammatory reaction, as well as controlling the other sequelae of the inflammation, most commonly elevated intraocular pressure. While the corneal inflammation associated with IK resolves spontaneously, the use of topical corticosteroids shortens the duration and the severity of the corneal inflammation. Studies have shown that the visual outcome is better and recurrences are fewer in patients who are treated with topical corticosteroids in a tapering fashion over a long period of time. The usual antiglaucoma medications may be used as needed to control intraocular pressure.
- Tuberculous IK also responds well to topical corticosteroid treatment. Systemic therapy is indicated using the recommended multidrug regimens.
- For patients with lepromatous IK, in addition to systemic treatment using dapsone, clofazimine, and rifampin, local treatment, including topical corticosteroids, may be used with caution due to the presence of neurotrophic disease and its deleterious effect on the corneal epithelium and wound healing.
- Treatment of Lyme disease includes the appropriate systemic antibiotic therapy, which is based on the stage of the illness and topical anti-inflammatory medications (eg, corticosteroids), which act to reduce the local morbidity as in the other forms of IK.
- Treatment of Acanthamoeba keratitis includes discontinuation of infected contact lenses, as well as using various antibiotic, antifungal, and antiparasitic topical and systemic medications. The medications may need to be continued for a significant length of time, and, typically, Acanthamoeba remains a very difficult infection to treat.
- The various parasitic causes of IK share systemic antiparasitic therapy as the basis of treatment. In cases of onchocerciasis, systemic treatment with ivermectin is the accepted standard of care.
- Leishmania requires systemic treatment with sodium stibogluconate, or meglumine antimonate may be combined with the same medications topically to treat keratitis.
- Treatment of IK due to trypanosomiasis is via the systemic antiprotozoal agents (eg, suramin, nifurtimox).
- Microsporidia remains a very rare cause of IK, and treatment options vary from systemic antiparasitic agents to surgical reconstruction with penetrating keratoplasty.
- Treatment of herpetic stromal disease has been described as part of the Herpetic Eye Disease Study (HEDS). Topical steroids were found to be beneficial when combined with topical antiviral agents in the treatment of herpetic stromal disease, but oral acyclovir was not found to have any additional benefit when combined with topical corticosteroids and topical antiviral agents (eg, trifluridine). Oral acyclovir does appear to reduce the likelihood of recurrent herpetic disease.
Surgical Care
In cases of permanent corneal opacity, corneal transplantation is an option, but it should be performed only when the ocular inflammation has become quiescent to prevent postoperative complications, such as rejection and graft failure.
Consultations
Rheumatologic and ear, nose, and throat (ENT) consultations should be obtained in suspected cases of Cogan syndrome. Infectious disease consultation may be beneficial in cases of unusual infections.
Medication
A wide variety of medications may be used to treat IK, with the specific agent selected based on the particular etiology of the condition. It is strongly recommended that systemic treatment be initiated and maintained by an internist, an infectious disease specialist, or a rheumatologist.
Although parasites are unusual causes of IK in the United States, in developing countries, the incidence is higher. Antiparasitic agents have been shown to be helpful in eradicating the immunologic stimulus and in preventing other associated ocular morbidity. Consultation with an infectious disease specialist is recommended in cases of suspected parasitic keratitis.
Corticosteroids
Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.
Prednisolone acetate 1% (PredForte)
Treats acute inflammations following eye surgery or other types of insults to eye.
Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
In cases of bacterial infections, concomitant use of anti-infective agents is mandatory; if signs and symptoms do not improve after 2 days, reevaluate patient. Dosing may be reduced, but advise patients not to discontinue therapy prematurely.
Adult
1 gtt in the affected eye, ranging from qh to qd in tapering doses
Pediatric
Administer as in adults
Effects may decrease in patients taking phenytoin, barbiturates, and rifampin
Documented hypersensitivity; epithelial herpes simplex keratitis; fungal or mycobacterial keratitis
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May elevate IOP and increase incidence of cataract formation
Antibiotics
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Antibiotics, such as penicillin, may be used in cases of IK secondary to untreated tertiary syphilis.
Penicillin (Pfizerpen)
Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms.
Adult
Primary/secondary syphilis: 2.4 million U (1 dose)
Tertiary syphilis: 2.4 million U/wk for 3 wk
Pediatric
Congenital syphilis: 50,000 U/kg
Probenecid can increase effects of penicillin; coadministration of tetracyclines can decrease effects of penicillin
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Avoid intra-arterial or IM injection; caution in impaired renal function
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. Bacteriostatic and bactericidal against Mycobacterium leprae.
Adult
100 mg PO qd
Pediatric
Not established; dosage is proportional to adult dose
May inhibit anti-inflammatory effects of clofazimine; hematologic reactions may increase with folic acid antagonists, eg, pyrimethamine (monitor for agranulocytosis during the second and third months of therapy); probenecid increases dapsone toxicity; trimethoprim with dapsone may increase toxicity of both drugs; due to increased in renal clearance, dapsone levels may significantly decrease when administered concurrently with rifampin
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Perform weekly blood counts (first month), followed by monthly WBC counts (6 mo) and then semiannually; discontinue if significant reduction in platelets, leukocytes, or hematopoiesis is seen; caution in methemoglobin reductase deficiency, G-6-PD deficiency (patients receiving >200 mg/d), or hemoglobin M due to high risk for hemolysis and Heinz body formation; caution in patients exposed to other agents or conditions (eg, infection, diabetic ketosis) capable of producing hemolysis; peripheral neuropathy can occur (rare); phototoxicity may occur when exposed to UV light
Rifampin (Rifadin, Rimactane)
For use in combination with at least one other antituberculous drug; inhibits DNA-dependent bacterial but not mammalian RNA polymerase. Cross-resistance may occur.
Treat for 6-9 months or until 6 months have elapsed from conversion to sputum culture negativity.
Adult
10 mg/kg PO qd; not to exceed 600 mg/d for several months, depending on treatment regimen
Pediatric
10-20 mg/kg PO qd; not to exceed 600 mg/d
Induces microsomal enzymes, which may decrease effects of acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, oral contraceptives, corticosteroids, mexiletine, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, clofibrate, quinidine, dapsone, tazobactam, sulfonylureas, theophyllines, tocainide, and digoxin; blood pressure may increase with coadministration of enalapril; coadministration with isoniazid may result in higher rate of hepatotoxicity than with either agent alone (discontinue one or both agents if alterations in LFTs occur)
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Obtain CBCs and baseline clinical chemistries prior to and throughout therapy; in liver disease, weigh benefits against risk of further liver damage; interruption of therapy and high-dose intermittent therapy are associated with thrombocytopenia that is reversible if therapy is discontinued as soon as purpura occurs; if treatment is continued or resumed after appearance of purpura, cerebral hemorrhage or death may occur
Antivirals
Antiviral medications, such as trifluridine and acyclovir, and its derivatives, valacyclovir and famciclovir, have shown activity against herpes simplex.
Trifluridine (Viroptic)
A fluorinated pyrimidine nucleoside with in vitro and in vivo activity against HSV1 and HSV2. Interferes with DNA synthesis.
Adult
1 gtt in affected eye(s) q2h, followed by tapering as epithelial keratitis improves
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause mild, local irritation of conjunctiva and cornea upon instillation
Acyclovir (Zovirax)
Synthetic purine nucleoside analogue with in vitro and in vivo activity against HSV1, HSV2, and varicella-zoster virus. Inhibitory activity is highly selective due to its affinity for the enzyme thymidine kinase encoded by HSV and VZV. Following biological conversion of acyclovir to acyclovir triphosphate, the new compound inhibits viral DNA synthesis.
Adult
400 mg PO 5 times/d
Pediatric
Not established
Concomitant use of probenecid or zidovudine prolongs half-life and increases CNS toxicity of acyclovir
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal failure or when using nephrotoxic drugs
Valacyclovir (Valtrex)
Prodrug rapidly converted to the active drug acyclovir. More expensive but has a more convenient dosing regimen than acyclovir.
Adult
500 mg PO bid
Pediatric
Not established
Probenecid, zidovudine, or cimetidine coadministration prolongs half-life and increases CNS toxicity of valacyclovir
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal failure and coadministration of nephrotoxic drugs; associated with onset of hemolytic uremic syndrome
Famciclovir (Famvir)
Prodrug that when biotransformed into active metabolite, penciclovir, may inhibit viral DNA synthesis/replication.
Adult
125-250 mg PO bid
Pediatric
Not established
Coadministration of probenecid or cimetidine may increase toxicity; coadministration increases bioavailability of digoxin
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal failure or coadministration of nephrotoxic drugs
More on Keratitis, Interstitial |
| Overview: Keratitis, Interstitial |
| Differential Diagnoses & Workup: Keratitis, Interstitial |
 Treatment & Medication: Keratitis, Interstitial |
| Follow-up: Keratitis, Interstitial |
| References |
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References
Cali A, Meisler DM, Lowder CY, Lembach R, Ayers L, Takvorian PM, et al. Corneal microsporidioses: characterization and identification. J Protozool. Nov-Dec 1991;38(6):215S-217S. [Medline].
Cogan DG, Dickersin GR. Nonsyphilitic interstitial keratitis with vestibuloauditory symptoms. A case with fatal aortitis. Arch Ophthalmol. Feb 1964;71:172-5. [Medline].
Cogan DS. Syndrome of nonsyphilitic interstitial keratitis and vestibuloauditory symptoms. Arch Ophthalmol. 1945;33:144-9.
Dekkers NW, Treskes M. Measles keratitis. Ophthalmol Clin North Am. 1994;74:574.
Dinis da Gama R, Cidade M. Images in clinical medicine. Interstitial keratitis as the initial expression of syphilitic reactivation. N Engl J Med. Jun 6 2002;346(23):1799. [Medline].
Ffytche T. Ocular leprosy--the continuing challenge. Int Ophthalmol. Sep 1991;15(5):289-93. [Medline].
Goegebuer A, Ajay L, Claerhout I, Kestelyn P. Results of penetrating keratoplasty in syphilitic interstitial keratitis. Bull Soc Belge Ophtalmol. 2003;(290):35-9. [Medline].
Helm CJ, Holland GN. Ocular tuberculosis. Surv Ophthalmol. Nov-Dec 1993;38(3):229-56. [Medline].
Jones BR, McGill JI, Steele AD. Recurrent suppurative kerato-uveitis with loss of eye due to infection by Acanthamoeba castellani. Trans Ophthalmol Soc U K. Jul 1975;95(2):210-3. [Medline].
Labetoulle M, Offret H, Bournerias I, Frau E. Rapid improvement of chronic interstitial keratitis with acitretin. Br J Ophthalmol. Dec 2002;86(12):1445-6. [Medline].
Lee ME, Lindquist TD. Syphilitic interstitial keratitis. JAMA. Nov 24 1989;262(20):2921. [Medline].
Matoba AY. Ocular disease associated with Epstein-Barr virus infection. Surv Ophthalmol. Sep-Oct 1990;35(2):145-50. [Medline].
North DP. The treatment of interstitial keratitis. Br Med J. Jul 3 1954;4878:7-9. [Medline].
Norton EW, Cogan DG. Syndrome of nonsyphilitic interstitial keratitis and vestibuloauditory symptoms; a long-term follow-up. AMA Arch Ophthalmol. May 1959;61(5):695-7. [Medline].
Orsoni JG, Zavota L, Manzotti F, Gonzales S. Syphilitic interstitial keratitis: treatment with immunosuppressive drug combination therapy. Cornea. Jul 2004;23(5):530-2. [Medline].
Pepose JS. Herpes simplex keratitis: role of viral infection versus immune response. Surv Ophthalmol. Mar-Apr 1991;35(5):345-52. [Medline].
Rabb MF, Fine M. Penetrating keratoplasty in interstitial keratitis. Am J Ophthalmol. Jun 1969;67(6):907-17. [Medline].
Roizenblatt J. Interstitial keratitis caused by American (mucocutaneous) leishmaniasis. Am J Ophthalmol. Feb 1979;87(2):175-9. [Medline].
Tamesis RR, Foster CS. Ocular syphilis. Ophthalmology. Oct 1990;97(10):1281-7. [Medline].
Taylor HR, Semba RD, Newland HS, Keyvan-Larijani E, White A, Dukuly Z, et al. Ivermectin treatment of patients with severe ocular onchocerciasis. Am J Trop Med Hyg. May 1989;40(5):494-500. [Medline].
Zaidman GW. The ocular manifestations of Lyme disease. Int Ophthalmol Clin. 1993;33(1):9-22. [Medline].
Further Reading
Keywords
interstitial keratitis, IK, syphilitic keratitis, Cogan syndrome, syphilitic disease, syphilis, herpes
