Year : 1982 | Volume
: 30 | Issue : 4 | Page : 209--211
Antiviral agents in herpes simplex keratitis
West, Virginia, USA
V K Raju
|How to cite this article:|
Raju V K. Antiviral agents in herpes simplex keratitis.Indian J Ophthalmol 1982;30:209-211
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Raju V K. Antiviral agents in herpes simplex keratitis. Indian J Ophthalmol [serial online] 1982 [cited 2023 Sep 21 ];30:209-211
Available from: https://journals.lww.com/ijo/pages/default.aspx/text.asp?1982/30/4/209/29430
Simple mechanical removal of the disease , epithelium, chemical cauterization and thermal cautery have been used for many years. Although epithelial debridement is still prefer�red by many ophthalmologists, there has been a widespread growing use of antiviral agents in epithelial keratitis. Currently three such agents are available for clinical use. These are : [ododeoxyuridine (IDU) : Adenine arabinoside (ARA-A or Vidarabine); and trifluorothymidine (TFT or F3-TDR), which is also the most recently introduced agent.
Each of these anti-viral agents and their therapeutic effect on Herpes Simplex keratitis are discussed separately as follows
1. Iododeoxyuridine (IDU)
Early experiments with IDU in rabbits stimulated many experiments and clinical trials. IDU causes healing of the keratitis within 10 days in 55 . 70% of cases. This is in comparison to 22-26% spontaneous cure rate.
IDU is effective in controlling the disease if therapy is started early, but corneas may per�forate from the disease even while undergoing drug therapy. IDU therapy of active herpetic disease can decrease the number of viral isola�tes to less than 4% and in vitro IDU can in�hibit cell and virus growth, which suggests that one of the beneficial effects of this drug may be attributed to a simultaneous cauterizing action on the virus and the epithelial cells. IDU is also known to adversely affect the metabolism of corneal epithelial cells, because these cells also take up the drug as well as the virus.
It was also discovered that the drug was not successful in the treatment of deep stromal disease because of its poor solubility.
IDU acts by competitively inhibiting the uptake of thymidine into the DNA molecule producing a faulty DNA chain which cannot function in infection producing viruses. It gradually became apparent that IDU was not a cure for primary disease. In addition to its poor solubility, IDU is topically toxic, unsta�ble, cannot eliminate the virus from the eye, and is more toxic in dry eye patients. Further�more, IDU is known to cause drug allergy, stenosis of lacrimal punctum, follicular con�junctivitis, narrowing of meibomian gland orifices, inhibition of keratocyte mitosis, inhi�bition of corneal stromal repair, and retarda�tion of corneal epithelial regeneration. It has also produced resistant virus strains.
2. Adenine arabinoside : (ARA-A, Vidarabine)
Because of the many problems associated with IDU new and more effective drugs for treatment of herpetic keratitis have been exa�mined. ARA-A was initially developed as an anti cancer drug in the early 1960's ARA-A (9-B-D-arabinofuranosyladenine) appears to function as a chain terminator preventing the lengthening of the DNA chain. It also func�tions as an inhibitor of DNA polymerise by acting as an analog of ATP. Its maior break�down product, adenine arabinoside hypoxan�thine (ARA-HX) is still active against the herpes virus but is less effective.
ARA-A-Hx has been found to be more soluble but less effective than ARA-A. In many clinical studies of ocular herpes simplex, results were the same whether stromal disease was treated with IDU or ARA-A. In addition ARA-A has been found to be effective against IDU resistant viruses in vitro as well as in clini�cal studies. ARA-A appears to be relatively nontoxic without cross allergenicity to IDU. It can be used intravenously to treat herpetic kerato uveitis. Because of the few side effects of this drug, its low toxicity, lack of cross allergenicity, and its effectiveness in cases unresponsive to IDU, ARA-A has become one of the major durgs used to treat herpes simplex keratitis.
3. Trifluoro thymidine : (TFT, F3T, F3TDR)
This new drug is more potent and more active than IDU in experimental animals. In its nucleotide form, HT is a potent inhibitor of thymidulate synthetase, thereby inhibiting both viral and host DNA synthesis. It is also incorporated directly into viral and cellular DIA, thus producing defective viral progeny and toxic side effects in normal host tissues.Various studies indicate that F3T is more effective than 1DU. It was also found that F3T was effective in cases where IDU or ARA-A therapy has failed. There is no cross toxicity or allergenicity among HT, IDU or ARA-A.
F3T is twice as potent and 10 times more soluble than IDU in a 1% solution. Because of high intraocular penetration it is effective in the treatment of herpetic iritis.
Clinical approach for the management of herpes simplex keratitis
1. Dendric ulcer without stromal involvement
Mechanical epithelial debridement and pressure patching : re advised as primary therapy. IDU ointment (0.5%) 5 times a day may also be used. If there is no improvement in the lesion in 5 days, curettage of the epithelium and patching may be employed If F3T or ARA-A are available, they may be employed after the curettage of the epithelium.
2. Stromal keratitis
Without antiviral therapy, 50% of the stromal disease cases would resolve spont�aneously but may take many months. Stromal involvement is accompanied by severe pain, deep edema, keratie precipitates, ciliary injection, and peripheral corneal vasculariza�tion. In these cases, curettage and debridement of the epithelium are not successful. The deep stromal disease and iritis may be treated with judicious use of cortico steroids in combination with antiviral agents. Topical antibiotics should be employed when topical steroids are being used.
3. Disciform keratitis and uveitis
This condition is considered to be an anti�gen antibody reaction. The patient presents with poor vision, painful eye, stromal edema in a disciform pattern overlying endothelial KP's. The epithelium may or may not be intact. This condition may be treated with topical steroids or with non steroid anti-infla�minatory agents, such as phenylbutazone, aspirin, or indomethacin. When topical steroids are used, concomitant use of prophy�lactic antibiotics and antiviral agents is advised. A serious problem with steroids is that once the kerato uveitis has been treated with steroids it will be difficult to control recurrences with�out again using steroids. Cycloplegics are indicated for iritis.
4. Metaherpetic ulcer (post herpetic erosion)
Metaherpetic ulcers are sterile and are secondary to the preceding viral and inflam�matory damage to the basement membrane. If the basement membrane is damaged during the infection it heals slowly and retards the healing of the overlying epithelium. As there is no multiplying virus in this disease, antiviral therapy in the absence of concomitant steroid is not indicated. The greatest danger in metaherpetic ulcer is collagenolytic activity with subsequent corneal stromal melting and perforation. Therapeutic soft contact lenses have greatly increased tae frequency and rapi�dity of healing of these ulcers. Artificial tears should be instilled 4 times a day. Cycloplegics are used if iritis is present. It is wise not to use topical steroids. A conjunctival lap or penetrating keratoplasty should be done if everything else fails.
Herpes Simplex of the eye is a multifaceted disease with multiple pathogenic mechanisms. In primary infection and recurrent dendritic ulcers without stromal involvement, simple mechanical debridment and pressure patching are recommended either with or without antiviral agents. A brief account of currently available anti viral agents and management of some common forms of herpetic corneal disease are discussed.