Decrease in the risk of bilateral acute retinal necrosis by acyclovir therapy

We reviewed the course of 54 patients who had unilateral acute retinal necrosis at initial examination. Thirty-one patients were treated with acyclovir, whereas 23 were not. Of the 31 patients treated with acyclovir, 27 (87.1%) had fellow eyes that remained disease-free throughout a median follow-up of 12 months. Of the 23 patients not treated with acyclovir, seven (30.4%) had fellow eyes that remained disease-free throughout a median follow-up of 11 months. Survival analysis indicated that the fellow eyes of the group of patients treated with acyclovir were more likely to remain disease-free than the fellow eyes of the group not treated with acyclovir (P = .0013). Two years after initial onset, the proportion of fellow eyes that remained disease-free was 75.3% for the group treated with acyclovir and 35.1% for the group not treated with acyclovir. These results suggest that acyclovir treatment reduces the risk of involvement of the fellow eye in patients with acute retinal necrosis.     

Acyclovir treatment in stromal herpetic keratitis

Twenty-five patients with long standing deep stromal herpetic keratitis and iritis were treated with acyclovir (3%) ointment and corticosteroids. All patients healed in about two to four weeks, independent of the duration of the keratitis before acyclovir treatment and independent of the antiviral medication given previously. Recurrences could not be prevented by acyclovir treatment. No serious side effects of acyclovir were noted.     

Oral acyclovir (Zovirax) in herpes simplex dendritic corneal ulceration.

Sixty patients with simple dendritic corneal ulceration were randomly assigned to double blind treatment with either acyclovir tablets (400 mg) or acyclovir ophthalmic ointment administered five times daily. There was no significant difference in the proportions of patients healed in either treatment group (88.9% on oral acyclovir and 96.6% on acyclovir ointment). The median healing time was five days in both groups. No systemic or significant local side effects were noted in either treatment group. Trough levels of acyclovir in the tear fluid of those who received the oral preparation were within or above the range of mean in-vitro ID50 levels for herpes simplex virus type 1. We conclude that oral administration of acyclovir (400 mg, five times daily) may be an effective alternative to topical therapy in selected patients.     

Light adaptation and the luminance-response function of the cone electroretinogram

Corneal graft survival in 13 patients (14 eyes) receiving oral acyclovir following corneal transplantation for herpes simplex keratitis was compared to that in nine patients (9 eyes) who underwent penetrating keratoplasty for herpes simplex keratitis without receiving postoperative acyclovir. Mean age, duration of disease, and time of follow-up did not differ in the two groups. There were no recurrences of herpes simplex keratitis in any patient receiving acyclovir during a mean follow-up of 16.5 months compared to a 44% (4/9) recurrence rate in patients without acyclovir during a mean follow-up of 20.6 months (p < 0.01). Graft failure occurred in 14% (2/14) of acyclovir treatment eyes and in 56% (5/9) of the grafts in patients not receiving acyclovir. Long term prophylactic oral acyclovir significantly decreased the recurrence of herpes simplex keratitis and reduced corneal graft failure in patients with a history of recurrent herpes simplex keratitis who underwent corneal transplantation.Abbreviations ACV acyclovir - HSK herpes simplex keratitis - PK penetrating keratoplasty Presented as a paper at The American Academy of Ophthalmology, annual meeting in Anaheim, California 13–17 October 1991.     

Pharmacokinetics of oral acyclovir (Zovirax) in the eye.

Patients due for cataract extraction received 5 doses of 400 mg acyclovir (Zovirax) orally during the 24 hours prior to surgery. Aqueous humour levels of acyclovir (mean 3.26 microM) were well above the normal ED50 range for herpes simplex virus type 1, and showed a significant correlation with plasma concentrations (mean 8.74 microM). There was also a correlation between the age of the patient and the concentration of acyclovir in the plasma. Oral acyclovir was well tolerated.     

Evaluation of the effects of acyclovir and/or human amniotic membrane on herpes virus culture and quantitative virus inactivity by real-time polymerase chain reaction

AIM: To investigate the permeability of amniotic membrane in herpes virus cell culture to acyclovir with real time polymerase chain reaction (RT-PCR).METHODS: Madin-Darby Bovine Kidney (MDBK) cell culture and Bovine Herpes Virus (BHV1) type 1 were used in the study. Cell cultures were grouped into two on the basis of herpes virus inoculation. Each group was sub-grouped into three. Amniotic membrane (V-HAM), acyclovir (V-A), and amniotic membrane and acyclovir (V-HAM-A) were applied to these subgroup cultures, respectively. After the application of the membrane and the drug, the cultures were evaluated at 24 and 48h for cytopathic effect positive (CPE+) with a tissue culture microscope. In the CPE (+) samples, the DNA was extracted for viral DNA analysis by RT-PCR.RESULTS: In control cultures without herpes virus CPE was not detected. Besides, amniotic membrane and acyclovir did not have cytotoxic effect on cell cultures. CPE were detected in Bovine Herpesvirus type-1 inoculated cell cultures after amniotic membrane and/or acyclovir application. DNA analysis with RT-PCR indicated that Cycle threshold (Ct) values were lower in the BHV1 and membrane applied group (amniotic membrane group< acyclovir group< membrane and acyclovir group). This showed that membrane did not have antiviral effect. The membrane and acyclovir cell culture groups with high Ct values indicated that membrane was permeable and had a low barrier effect to drug,CONCLUSION: In our in-vitro study, we found that amniotic membrane, which can be used in the treatment of corneal diseases, did not have antiviral effect. Besides, we detected that amniotic membrane was permeable to acyclovir in BHV-1 inoculated MDBK cell culture. However, more studies are necessary to investigate the quantitative effects of amniotic membrane and acyclovir.     

Intravenous acyclovir treatment for extensive herpetic keratitis in a liver transplant patient

Herpetic infection is a common complication among immune suppressed patients following heart, kidney and bone marrow transplantations,in leukemia patients, in AIDS patients, and during treatment with cytotoxic drugs. In the cases described in the literature, oral acyclovir was recommended as a treatment for the acute infection, as well as for prophylaxis. Intravenous acyclovir is not a routine treatment for herpetic keratitis, but is recommended for cases of insufficient clinical response to oral treatment, and defective absorption of acyclovir by the gastrointestinal tract. We present a patient who underwent 4 liver transplantations,was treated regularly with immunosuppressive drugs, and who developed extensive herpetic keratitits. The keratitis was resistant to both topical ointment and oral acyclovir treatment. Recovery was only achieved following the intravenous administration of acyclovir. We recommend intravenous acyclovir treatment at avery early stage for immune suppressed patients with extensive herpes simplex keratitis. This revised version was published online in July 2006 with corrections to the Cover Date.     

Oral Acyclovir in the Management of Herpes Simplex Ocular Infections

Acyclovir, an oral antiviral agent that inhibits viral DNA replication, was used to treat 27 patients (16 males, 11 females) (mean age, 50 years) with vision-threatening herpes simplex virus (HSV) infections. Twenty patients had active stromal keratitis or keratouveitis, four had controlled nonnecrotizing stromal keratitis but could not taper topical medications, and four eczema patients with previous HSV infections had intraocular surgery (1 of these patients also is included in the 20 with active stromal keratitis). All 20 patients with active stromal keratitis or keratouveitis improved on acyclovir, all four patients using acyclovir postoperatively were disease-free while on the drug, but only two of the four patients using acyclovir to assist tapering topical medications were successful. There has been only one recurrence during a cumulative 194 months while on acyclovir. Thirteen patients have remained on acyclovir, and three who stopped acyclovir had prompt recurrences. Acyclovir seems to be a promising adjunct antiviral agent for the treatment of recalcitrant epithelial, stromal, or uveal disease secondary to HSV.     

Oral acyclovir for the management of herpes simplex virus keratitis in children

PURPOSE: To evaluate the use of oral acyclovir in pediatric patients with herpes simplex virus (HSV) keratitis. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Seven pediatric patients seen at the University of Minnesota Hospitals and Clinics with herpes simplex virus (HSV) infectious epithelial keratitis between January 1992 and October 1998. Patient ages ranged from 6 weeks to 5 years at time of presentation with a median of 1.7 and mean of 1.9 years. INTERVENTION: All patients received oral acyclovir; six of seven patients also received topical antiviral medications. Three of seven patients had topical antiviral therapy fail before being placed on oral acyclovir, and the remaining four patients were placed on oral acyclovir primarily. RESULTS: All patients showed resolution of HSV infectious epithelial keratitis. Three patients have been maintained on prophylactic dosage of oral acyclovir because of recurrent disease or because they have been chronically treated with topical corticosteroids for immune stromal keratitis. All patients tolerated acyclovir well, and there were no adverse reactions. CONCLUSIONS: Oral acyclovir is useful in treating HSV infectious epithelial keratitis in pediatric patients. It is beneficial in treating infectious epithelial keratitis and prophylactically either while treating with topical corticosteroids for immune stromal keratitis or for preventing recurrent infectious epithelial keratitis.     

Acyclovir (Zovirax) in herpetic disciform keratitis.

Forty patients with disciform keratitis were randomly assigned to double-blind treatment with 3% acyclovir and 0.01% betamethasone drops or acyclovir and matching placebo. All patients who received the combination healed in a median time of 21 days, while 11 of 19 patients who received acyclovir alone were withdrawn because their condition remained static or worsened (p less than 0.001). The combination therapy produced a faster rate of healing (p = 0.004); other clinical parameters also improved more favourably in the combination treatment group. Three patients had mild transient punctate keratopathy, but no serious adverse effects were seen despite treatment for a median duration of 28 days in the acyclovir group and 38 days in the combined therapy group. A combination of acyclovir and dilute steroid drops is effective in the management of disciform keratitis.     

Acute retinal necrosis

Five patients with the acute stages of acute retinal necrosis underwent vitrectomy, with acyclovir in the infusion fluid, and the placement of a 360 degrees scleral buckle after intravenous therapy with acyclovir. Anatomic reattachment was achieved in all patients, and improvement over preoperative visual acuity was obtained in four. Recommendations for the treatment of acute retinal necrosis include a high index of suspicion in healthy patients with retinitis, early diagnosis, early intravenous therapy with acyclovir, early pars plana vitrectomy with the use of intravitreal acyclovir in the infusion fluid, and a 360 degrees scleral buckling procedure.     

Oral acyclovir in the management of dendritic herpetic corneal ulceration.

A controlled trial of oral acyclovir in herpetic dendritic corneal ulcers was carried out on 31 patients. All patients received minimal wiping debridement of the ulcer, following which they were randomly allocated to receive either oral acyclovir or placebo for 7 days. At the end of treatment 67% of dendritic ulcers in patients receiving acyclovir had healed compared with 43% in placebo recipients. The proportion of ulcers healed in the 2 groups at 7 days showed no significant difference (p = 0.18), but the rate of healing was significantly faster in acyclovir group (p = 0.03).     

Vitreous penetration of orally administered valacyclovir

PURPOSE: To investigate the vitreous penetration of acyclovir, the active metabolite of valacyclovir, after oral administration of valacyclovir. DESIGN: Prospective, interventional case series. METHODS: Ten patients scheduled for elective pars plana vitrectomy at a single academic institution were given three oral doses of valacyclovir 1000 mg eight hours apart the day before surgery, with a fourth dose on the morning of surgery. Blood and undiluted vitreous samples were obtained during surgery and subsequently were analyzed with high-performance liquid chromatography to determine the concentrations of acyclovir present. RESULTS: Ten eyes of 10 subjects ranging in age from 46 to 83 years were included. All patients had normal renal and hepatic function as confirmed by metabolic panels obtained before surgery. Mean serum acyclovir concentration +/- standard deviation was 4.41 +/- 0.88 microg/ml (range, 3.18 to 5.92 microg/ml), mean vitreous acyclovir concentration was 1.03 +/- 0.23 microg/ml (range, 0.67 to 1.33 microg/ml), and mean vitreous-to-serum concentration ratio of acyclovir was 0.24 +/- 0.06 (range, 0.16 to 0.34). CONCLUSIONS: Orally administered valacyclovir results in substantial vitreous penetration of acyclovir. The vitreous concentrations achieved in noninflamed eyes are within the reported inhibitory ranges for most strains of herpes simplex 1, herpes simplex 2, and varicella zoster virus. This suggests that orally administered valacyclovir may be an alternative to intravenous acyclovir in the treatment of acute retinal necrosis.     

Randomised double-blind trial of acyclovir and idoxuridine in dendritic corneal ulceration.

The results of a randomised double-blind clinical trial of 3% acyclovir and 0.5% idoxuridine (IDU) ophthalmic ointments in 60 patients with corneal dendritic ulceration are presented. Ulcers in all 30 patients treated with acyclovir healed compared with 22 (76%) of 29 patients treated with IDU (P < 0.01). Patients treated with acyclovir healed more rapidly (average 4.4 days) than those who received IDU (average 9.2 days) (P < 0.01). No serious side effects were observed, though transient stinging was recorded in 8 patients receiving acyclovir and in 2 patients receiving IDU. Other side effects in the IDU treated group were watering in 2 patients and superficial punctate erosions in 6 patients.     

Effect of Prolonged Oral Acyclovir Treatment in Acute Retinal Necrosis

Background: To examine the effectiveness of prolonged oral acyclovir treatment in patients with acute retinal necrosis (ARN).

Methods: Fifty-five ARN patients (62 eyes) who had been treated with short-term or long-term oral acyclovir were identified in this retrospective study: one group treated with prolonged oral acyclovir (≥14 weeks) and the other group treated with a shorter duration of oral acyclovir (<14 weeks). The authors examined whether the prolonged treatment reduced the involvement of the contralateral eye. They also evaluated prognostic factors for visual outcome.

Results: Prolonged oral acyclovir treatment reduced the involvement of the contralateral eye (p =?.036). The visual outcome was influenced by the timing of treatment initiation after symptom onset (p =?.030), the age of the patient (p =?.027), the area of retinal disease (p =?.026), and the retinal detachment (p =?.002).

Conclusions: Prolonged oral acyclovir treatment had a significant role in preventing the involvement of the contralateral eye.     

Ocular penetration of acyclovir and its peptide prodrugs valacyclovir and val-valacyclovir following systemic administration in rabbits: An evaluation using ocular microdialysis and LC-MS

PURPOSE: To investigate the ocular penetration of acyclovir and its prodrugs following systemic administration and to elucidate the mechanism of penetration. METHODS: Hydrophilic peptide prodrugs of acyclovir were infused intravenously in New Zealand albino rabbits over 45 min at a dose equivalent to 30 mmoles/kg acyclovir. Aqueous and vitreous humor samples were obtained utilizing ocular microdialysis and blood samples were obtained from the mid ear vein using a cannula. RESULTS: The plasma bioavailability for acyclovir, valacyclovir and val-valacyclovir were similar with area under curve values being 896.24 (+/-143.58), 776.54 (+/-197.52), 824.69 (+/-217.43) min x micromoles/L respectively. Anterior segment area under curve values were 53.70 (+/-35.58), 139.85 (+/-9.43) and 291.05 (+/-88.13) min x micromoles/L respectively while the mean residence time values were 46.47 (+/-24.94), 76.30 (+/-7.24) and 188.39 (+/-80.73) min respectively. Vitreous levels of the prodrugs were not measurable. CONCLUSIONS: The valine and valine-valine ester prodrugs of ACV penetrated the anterior segment of the eye much better than acyclovir alone, probably via a carrier mediated transport mechanism.     

Synergistic antiherpetic effect of acyclovir and mycophenolate mofetil following keratoplasty in patients with herpetic eye disease: first results of a randomised pilot study

Purpose The main reasons for graft failure following penetrating keratoplasty in patients with herpetic eye disease are recurrence of herpetic disease and allograft rejection. In a randomised trial the effect of systemic acyclovir and mycophenolate mofetil (MMF) on these post-keratoplasty complications was evaluated.Patients and methods Patients with typical clinical findings of recurrent herpetic keratitis were enrolled in this single-centre study after contraindications to systemic immunosuppression were ruled out. In a prospective randomised trial 30 patients were treated in three groups. In group A patients received acyclovir 200 mg five times/day for 3 weeks. In group B patients were treated with acyclovir 200 mg five times/day for 1 year, and patients in group C received acyclovir 200 mg five times/day in combination with MMF 1 g twice daily for 1 year.Results In group A 3 patients experienced seven herpes recurrences. One patient had a moderate and one further patient a severe allograft rejection. In group B three severe allograft rejections were observed. Herpes recurrences did not occur while receiving acyclovir prophylaxis, but only once after the prophylaxis had been stopped. In group C no herpes recurrence was observed, and only two mild allograft rejections occurred while being under combined acyclovir—MMF therapy. Another mild and one moderate allograft rejection were observed after cessation of MMF.Conclusions These results demonstrate that systemic acyclovir protects the grafts from recurrences of herpetic disease as long as it is administered at efficient doses. Simultaneously administered mycophenolate mofetil does not trigger herpes recurrences and protects the graft from severe allograft rejections, but mild, less dangerous immune reactions may still occur while receiving MMF. The combination of systemic acyclovir and mycophenolate mofetil therefore is recommended for patients at high risk for herpes recurrence and allograft rejections.     

Acyclovir-resistant herpes simplex virus keratouveitis after penetrating keratoplasty.

PURPOSE: A case of acyclovir-resistant herpes simplex virus keratouveitis after penetrating keratoplasty is reported. METHODS: Resistance to acyclovir was evident clinically and was confirmed by in vitro susceptibility testing. The susceptibility of the herpes simplex isolates to acyclovir and foscarnet was determined by a dye uptake assay that measured cytopathic effect, and thymidine kinase activity was measured by a plaque autoradiography technique. RESULTS: The viral isolate from postoperative day 22 was susceptible to acyclovir and foscarnet, and showed normal thymidine kinase activity. Isolates from postoperative days 29 and 32 (coinciding with deterioration in clinical appearance) were resistant to acyclovir, susceptible to foscarnet, and deficient in thymidine kinase activity. CONCLUSION: Practitioners should be aware of the potential for the emergence of resistance in this setting; prophylaxis and rational alternate therapies are discussed.     

Oral acyclovir in the therapy of acute herpes zoster ophthalmicus. An interim report

A prospective, randomized, double-masked, placebo-controlled clinical trial was conducted to study the effects of oral acyclovir on 55 patients with acute herpes zoster ophthalmicus. Treatment with oral acyclovir resulted in more prompt resolution of signs and symptoms, particularly in patients treated within 72 hours after onset of skin rash (P less than 0.05), and shortened the duration of viral shedding (P = 0.02). Vesicular skin lesions involving other dermatomes (microdissemination) occurred in five (19%) placebo-treated patients but in no acyclovir-treated patients (P = 0.03). Interim analysis of this longitudinal study suggests that the incidence and severity of secondary ocular inflammatory disease was reduced by acyclovir. Prolonged observation of these patients is ongoing to determine if oral acyclovir reduces post-herpes zoster neuralgia or the late ocular complications of ophthalmic zoster.     

Herpes zoster ophthalmicus complicated by hyphema and hemorrhagic glaucoma

We treated two patients with herpes zoster ophthalmicus in whom hyphema and hemorrhagic glaucoma occurred. Case 1 complained of facial skin eruption, and was given intravenous acyclovir for 7 days. Hyphema and high intraocular pressure occurred in the left eye 10 days after the onset of the skin eruption. Case 2 had severe pain and blisters on her face, and was given intravenous acyclovir for 7 days. An intracameral hemorrhage and glaucoma developed in the right eye 15 days after the onset of the skin lesion. Intravenous acyclovir may be necessary for longer than 7-day periods if the iridocyclitis remains.