In vitro studies have demonstrated a relative resistance of herpes simplex virus type 2 to antiviral therapy when compared with herpes simplex virus type 1. The in vivo studies, however, show an excellent therapeutic response to both antiviral drugs in experimentally induced viral keratoconjunctivitis.

Animals↗

PubMed1976

Intraocular penetration of the soluble antiviral, Ara AMP.

Earlier studies on intraocular penetration of the antiviral drugs idoxuridine and vidarabine (formerly Ara A) reveal that either inactive metabolites from the former or very low levels of less active metabolites from the latter actually enter the aqueous. Additionally, to achieve therapeutic levels, systemically administered vidarabine must be given in large fluid volumes because of poor solubility. The present time-curve study on the intraocular penetration of the highly soluble nucleotide form of vidarabine, Ara AMP, reveals that, in rabbits, very high aqueous levels of the antiviral metabolite, Ara Hx, are achieved after intravenous does in small fluid volume. Moderately low levels are attained after subconjunctival injection, extremely low levels are attained after subconjunctival injection, and extremely low levels are present after topical administration. This indicates that intravenous and possibly subconjunctival injection may be useful in treatment of deep ocular herpetic disease.

Administration, Topical↗

PubMed1976

Penetrating keratoplasty in acute herpetic corneal performations.

Central corneal perforations have traditionally been managed by conjunctival flaps, tissue adhesives, soft contact lenses, corneal patches and other conservative measures for the immediate preservation of the eye. An alternative method of treatment is immediate penetrating keratoplasty. We present the result of immediate keratoplasty for 25 eyes referred with acute central corneal perforations, 20 of herpetic origin and 5 with a chemical burn or dry eye syndrome. In all cases, the eye was successfully preserved. Twelve of 20 grafts (60%) for herpetic perforation went on to eventual clear grafts as opposed to 1 of 5 grafts (20%) in the dry eye or chemically burned patients. Significant complications encountered included cataract formation, secondary glaucoma and persistent epithelial defects; however, these should not preclude eventual restoration of good visual acuity. Penetrating keratoplasty in acutely inflamed and perforated eyes used to lead to angle closure and secondary glaucoma in a considerable number of cases, sometimes progressing to total disaster. We have shown that if enough corticosteroids are given immediately postoperatively, the risk for angle closure is not significant.

Administration, Topical↗

PubMed1976

Ara AMP- a highly soluble new antiviral drug.

While vidarabine (Ara A) is in several ways superior to idoxuridine (IDU) it still has the disadvantages of rapid inactivation and poor solubility. The monophosphate ester or vidarabine, Ara AMP, however, is metabolized very slowly in humans and is extremely soluble with good tissue penetrance. The present study indicates that Ara AMP drops are equipotent or superior to vidarabine ointment in treatment of type 1 and type 2 herpes simplex keratitis. While iritis was significantly less in all treated groups, a suspicion of chemical side effect was raised but could not be proven in subsequent toxicity tests.

Adenosine Monophosphate↗

PubMed1975

Pilocarpine ocusert system for sustained control of ocular hypertension.

A pilocarpine-containing, polymermembrane unit (Ocusert) was evaluated in 29 patients with open-angle glaucoma. Patients placed the system in the cul-desac once a week; they retained it well and tolerated its continuing use without appreciable difficulty. Intraocular pressure was controlled satisfactorily by the use of systems releasing either 20mug/hr or 40mug/hr of pilocarpine; concomitant medications were used where indicated. Side-effects from the ocular therapeutic system were minimal or absent. An attempt to correlate eyedrop strength required for ocular pressure control with the release rate of the Ocusert system required was generally unsuccessful. All the data on pressure response to the system, however, indicate that it provides control comparable to that achieved with the commonly used pilocarpine eyedrop concentrations.

Consumer Behavior↗

PubMed1975

Idoxuridine ocular insert therapy. Use in treatment of experimental Herpes simplex keratitis.

Therapy of acute Herpes simplex keratitis in rabbits with idoxuridine-releasing ocular inserts showed that an application rate of 30mug/hr gave significantly better results than conventional treatment with idoxuridine drops and ointment while exposing the eye to 40% less drug. Delivery rates lower than this were equal or not as effective as drop and ointment therapy and rates up to 100 mug/hr did not produce significantly better results than rates of 30mug/hr. Serial viral cultures demonstrated the persistence of virus beyond the period of clinical resolution of disease in all treatment groups, indicating that therapy should be continued longer than apparent resolution of disease.

Animals↗

PubMed1975

Clinical evaluation of adenine arabinoside and idoxuridine in the treatment of ocular herpes simplex.

A Double-blind clinical study comparing idoxuridine (IDU) with adenine arabinoside (ara-A) in treating 54 routine herpetic ulcers, and an open ara-A therapy study of 58 herpetic ulcers in patients intolerant of or resistant to IDU, was carried out over a four-year period. There was no significant difference in healing time between IDU-treated eyes (11.5 days) and ara-A-treated eyes (12.4 days) in the double-blind study but there were four moderate to marked adverse reactions to IDU and only two mild reactions to ara-A. In the open-drug study 21 patients who were intolerant of IDU because of allergy or toxicity and 37 patients who had ulcers resistant to or deteriorating on IDU therapy used ara-A up to 192 days without any adverse reaction. Mean healing time was 10.6 days for 49 of 57 patients in the efficacy analysis. Eight patients developed trophic ulcers that responded to soft lens therapy and one was dropped from the study because his initial disease could not be distinguished from severe IDU-induced keratitis.

Adolescent↗

PubMed1975

Diagnosis and management of herpes simplex ocular infection.

The multifaceted nature of ocular herpes simplex has become more clearly defined in recent years, as it has become apparent that it is a disease characterized by both infectious and immune components. Therapy Therapy of infectious epithelial dendritic-geographic disease is generally gentle debridement of the ulcer followed by antimetabolite chemotherapy with IDU or Ara A. Tropic (metaherpetic) ulceration may occur postinfection and is caused by sterile basement membrane damage, which makes it difficult for the epithelium to heal across the damaged ulcer base. Therapy is generally that of recurrent erosion and involves patching, soft contact lenses, and lubricating drops and ointments. Stromal disease may be (1) viral interstitial keratitis, which is slowly responsive to antiviral therapy, or (2) immune disciform reaction, which may or (hopefully) may not necessitate steroid therapy with prophylactic antiviral and antibiotic cover. Herpetic iritis may occur alone or with any form of corneal disease. While it is generally felt to be caused by intact intraocular virus, therapy is still steroid-oriented for lack of more effective and penetrating antiviral drugs. Antimetabolite-induced medicamentosa may mimic almost any form of herpetic disease and should be ruled out in any differential diagnosis of a patient deteriorating under therapy.

Administration, Topical↗

PubMed1975

Recent advances in antiviral therapy.

It has been demonstrated in clinical trials that (1) the antimetabolites Ara A and F3T are both significantly better than IDU in the treatment of many forms of ocular herpes, and (2) they are not significantly different from each other. In preclinical trials, the IDU ocular insert also has shown itself to be significantly better than IDU drop-ointment therapy, while exposing the eye to 40 percent less drug and adding tremendous convenience and ease of compliance by patients to an otherwise difficult medication schedule. Both photodynamic inactivation and cryotherapy have been shown in clinical trials to have notable therapeutic efficacy against herpes, but undesirable and occasionally severe side-effects have slowed down and possibly stopped the further development of these techniques.

Antiviral Agents↗

PubMed1975

Penetrating keratoplasty for herpetic keratitis: decision-making and management.

The outlook for keratoplasty in herpetic keratitis has improved significantly over the past decade. While only two out of three grafts in vascularized and regrafted eyes and in eyes with active disease are clear after two years, in quiet eyes with no significant vascularization, the success rate exceeds 80 percent. The significant factor in the improved results, in both favorable and unfavorable cases, is the improvement in surgical technique, involving the operating microscope, the 10-0 nylon suture, and the increased understanding of the pathophysiology of corneal grafting, which has resulted in more sophisticated postoperative care. In our experience, the routine use of high levels of topical steroids in the immediate postoperative period, followed by a rapid tapering of these medications, has been particularly successful.

Administration, Topical↗

PubMed1975