Systemic Antiviral Therapy Research Articles

Treatment of antiviral-resistant recurrent erythema multiforme with dapsone.

Recurrent erythema multiforme (REM) is a chronic disease characterized by frequent episodes of target cutaneous lesions in an acral distribution. Conventional treatment includes systemic corticosteroids and antiviral therapy. The aim of this study was to evaluate dapsone as a potential steroid sparing-agent for the treatment of REM after a failed trial of at least one antiviral therapy (acyclovir, famciclovir, or valacyclovir). A retrospective chart review was conducted on thirteen patients with a diagnosis of REM who underwent treatment with dapsone after failing at least one antiviral therapy. Out of 13 patients, 6 showed complete response (CR) and 5 showed partial response (PR). The underlying cause was identified in 5 patients with all showing at least PR. Adverse effects, observed in 4 patients, included fatigue, macrocytic anemia, anxiety, insomnia and involuntary movements, and drug-induced lupus erythematosus. A continuous course of dapsone, titrated up from 25 mg/day to a dose at which clinical improvement is seen with acceptable patient tolerance, is a viable steroid sparing-agent for REM treatment after a failed trial of antiviral therapy.

Effectiveness of platelet‐rich plasma treatment in patients with chronic corneal erosions, associated with Herpetic keratitis

Purpose3 courses of platelet‐rich plasma (PRP) instillations were investigated for their effect on corneal epithelialization, in cases, associated with Herpetic keratitisMethodsThe study involved 21 patients with chronical corneal erosions of Herpetic keratitis origin. Etiology was confirmed by immunosorbent immunoglobulins M, G assay for Herpes Simplex Virus 1,2, Cytomegalovirus and Virus Epstein ‐ Barrie. All patients had previous unsuccessful courses of reparative therapy. First step of treatment consist of local and systemic antiviral therapy (Gancyclovir eye gel 0.15% and Valcyclovir). After the antiviral therapy, common volume 15 ml. of blood, taken from patients cubital vein, was mixed with anticoagulant (Sodium citrate with Dextrosa), and undergone a double centrifugation for 4 min. at 3,500 rpm. Patients were receiving: PRP instillations 6 times a day in combination with subconjunctival injection ones a week, Sulfated glicosaminoglicans 0.01% 4 times a day, Dexpanthenol 5% 4 times a day. Course of treatment was 3 weeks, procedure of obtaining PRP was performed 1 time per week. Dynamic of the treatment was assessed by Efron scale (cornea fluorescein coloring at 5 sectors in points). The patient's condition before therapy was used as a control.ResultsThe average index of the corneal lesion before treatment was 9.7 points. After the 1st and 2nd procedure average lesion index was 8.2 and 5.9 points respectively. After 3 weeks, complete epithelization was observed in 12 patients. In 6 patients a gradual disappearance of the epithelial defects was shown after 5–6 courses. 3 patients did not respond to the treatment.ConclusionsPRP treatment showed positive dynamic in cases of previously unsuccessfully treated chronical corneal erosion.

Herpes zoster und postzosterische Neuralgie

Herpes zoster develops by endogenous reactivation of varizella zoster virus (VZV). Incidence increases with age. Females are more frequently affected than males. The reactivation rate in seropositive individuals is about 20 %. After ashort prodromal stage, herpetiform-grouped vesicles appear in segmental arrangement. Pain and paresthesia are typical zoster symptoms. Complications like bacterial superinfections, vasculopathy, paresis, and oculopathy may occur. During pregnancy herpes zoster is athreat for mother and child. Among elderly patients, cardiovascular risk is increased during the first week of herpes zoster infection. Postherpetic neuropathy is feared. Diagnosis can be made clinically and by the use of polymerase chain reaction. First-line treatment is systemic antiviral drug therapy with either acyclovir or brivudine. Adjuvant therapies consist of pain management and topical treatment.

Management of Cytomegalovirus Retinitis in HIV and Non-HIV Patients.

As CMVR continues to affect HIV-positive and non-HIV immunosuppressed patients, ophthalmologists must continue to tailor diagnostics and therapeutics to individual cases. In HIV-related disease, ocular fluid sampling and intravitreal drug delivery are considerations, but systemic antiviral therapy is paramount in the initial management from both ophthalmic and systemic morbidity standpoints. Non-HIV-related disease should be approached with a multidisciplinary team, including an ophthalmologist/vitreoretinal/uveitis specialist for consideration of intravitreal antiviral therapy with qualitative and quantitative aqueous PCR monitoring, and consideration of PCR genome sequencing for CMV strains that may become resistant to antiviral therapies from long-term antiviral prophylactic exposure. Hematologists or oncologists may help with patients who remain bone marrow-suppressed following transplantation or systemic chemotherapy. Because of related toxicities of the anti-CMV medications and immunosuppressive medications (eg, bone marrow suppression and cytopenias), infectious disease consultation can help in the treatment and monitoring of side effects.

The plce of immunomodulators in the treatment of ENT organs

Acute and chronic diseases of the upper respiratory tract account for a significant proportion of diseases both in adults and children. For example, in the United States, sinusitis is now the most widespread disease the incidence of which is higher than that of hypertension and arthritis (according to the National Center for Health Statistics, USA). At the same time, inefficacy of local and systemic antimicrobial and antiviral therapies due to polyvalent resistance and absence of new formulas in the market is becoming a pressing issue. Physical therapy and surgical techniques do not always lead to a desired outcome. A review of causes of failed effectiveness of ENT treatments supports the fact immunological reactivity of the patients has changed

Clinical efficacy of oral and topical acyclovir in herpes simplex virus stromal necrotizing keratitis.

Purpose:To evaluate the efficacy of systemic and topical antiviral therapy in the treatment of active herpes simplex virus (HSV) necrotizing stromal keratitis (NSK).Design:Prospective interventional case series.Methodology:Patients with a diagnosis of HSV NSK based on history and clinical findings were enrolled in the study. A standard protocol was used for microbiologic investigations. Ten weeks regime of systemic acyclovir and 2 weeks of topical acyclovir was given. Complete ophthalmic examination was performed at every visit. Outcome measures were a reduction in the area of infiltration and improvement in visual acuity.Results:Fifteen patients were enrolled in the study. The mean age of presentation was 51.53 years. The duration of symptoms at presentation ranged from 2 to 8 weeks. HSV1 DNA polymerase chain reaction was positive in 70% cases of those tested. Area of infiltration at trial entry and at the end of 2 weeks of antiviral treatment reduced significantly (P = 0.007). All patients showed a complete resolution of keratitis at the end of study.Conclusion:Topical and systemic acyclovir for treatment of NSK facilitates healing of ulceration. Topical steroids after initial antiviral therapy are safe and decreases inflammation and improve visual recovery. Early initiation of therapy has better outcomes as compared to late presentations.

Clinical presentations of Herpes Zoster Ophthalmicus (diagnosis and therapy)

To study and summarize clinical features of HZO (including the rate of complications and their nature) and to determine the relationship between clinical and laboratory data from these patients. The study included 133 patients with ophthalmic and neurological complications of HZO (group 1 (n=28) - retrospective analysis of outpatient records for the period 1995-2005; group 2 (n=95) - a prospective study for the period 2005-2015), who received a course of conservative treatment in either the Botkin City Hospital, branch № 1, or in the ophthalmic department of the Moscow herpes centre (Gerpeticheskiy Tsentr Ltd.). Laboratory tests were performed only in patients from group 2 and included: examination of biological fluids for six types of herpes viruses by polymerase chain reaction, examination of tears and urine for DNA of Chlamydia, Mycoplasma, and Ureaplasma, and serological blood testing for markers of herpes virus infection. Patients from group 1 were prescribed topical antiviral, antibacterial, and anti-inflammatory therapy, in rare cases - acyclovir per os. In group 2, the treatment included systemic antiviral medications and immune correction therapy. Anti-inflammatory therapy consisted of local and systemic non-steroidal agents (NSAIDs). The most common ophthalmic complications of HZO in both groups were stromal keratitis and keratoiridocyclitis, neurological - III and VI cranial nerves palsies. The duration of the disease in the first group ranged from 2 months to 3 years; in the second group, patients were divided into two subgroups: subgroup A with the disease duration of no more than one month (n=81) and subgroup B with the disease duration from 1.5 to 9 months (n=14). Varicella-zoster virus (VZV) DNA was present in tears and/or other biological fluids of patients from group 2 in more than 70% of cases (n=67). Particularly, in 27.4% of cases the virus was isolated in two fluids and in 7.4% of cases - in three fluids. The duration of virus production in tears and other biological fluids (saliva, blood, and urine) ranged from 10 days to 4 months. Topical non-steroidal anti-inflammatory drugs and systemic etiological treatment in case of intraocular inflammation in HZO patients may reduce the risk of severe consequences of VZV reactivation and help avoid recurrences later in life.

Giant extragenital Bowen’s disease

Giant extragenital forms of Morbus Bowen are extremely rare. The already described cases in the word literature are most commonly with periungual localization, as well as located on the foot and neck area. The clinical manifestation is presented most commonly by non-specific erythematous to erythematous-squamous plaques or papules, which is confusing to the clinician. From the pathogenic point of view, it is important to be confirmed or rejected the presence of human papilloma viruses (HPVs) in each case of affected patient, as this information is mandatory in respect to the adequate selection of the subsequent regimen. If HPVs are detected, systemic antiviral therapy could be initiated to reduce the size of the lesions before subsequent surgical eradication. A postoperative prevention through vaccination could be also considered additionally. In cases of HPV-negative giant extragenital forms of Morbus Bowen (as in the described patient), the focus should be on local immunomodulation by substances such as imiquimod, which reduce the size of the lesions, thereby creating optimal opportunities for their future surgical eradication. Other possible options described in the literature include topical application of 5-fluorouracil, photodynamic therapy, cryotherapy, and laser therapy (carbon dioxide laser). The choice of the most appropriate regimen should have been an individual decision of the clinician, considering also the location and the extent of the lesion.

Herpes Simplex Keratitis: Bilateral Effects.

disease. 2 It is plausible that viral reactivation occurred in both trigeminal ganglia and possibly the cornea, resulting in the presence of virus in both clinically affected and fellow eyes. The absence of clinically recognizable disease in fellow eyes would support the differences in nerve count, sensation, and ECD between affected and contralateral eyes. What is important about this study is the demonstration of the bilateral effects of HSK particularly in terms of ECD and corneal innervation. These bilateral effects of clinical unilateral HSK raise significant issues regarding treatment, prophylaxis, and management, particularly with regard to consideration of greater use of systemic antiviral therapy. Future work would be to longitudinally sample for HSV-1 and image the affected and unaffected areas of the cornea in the affected and fellow eyes, including other measurements of sensation in addition to mechanical touch such as temperature and chemical stimuli, which may be selectively altered in HSK. 4

Cytomegalovirus Retinitis in a Human Immunodeficiency Virus-negative Cohort: Long-term Management and Complications

Purpose: To examine the clinical outcomes achieved by using intravitreal ganciclovir injections combined with systemic anti-viral therapy in treating cytomegalovirus (CMV) retinitis in patients without human immunodeficiency virus (HIV) infection.Methods: Twenty-three eyes of 15 HIV-negative patients diagnosed with CMV retinitis were included in this retrospective study.Results: The median follow-up was 68 weeks (range, 12–156), and median number of injections was 10 (range, 2–22). The retinal lesions stopped progressing within 1–2 weeks following treatment. All of the eyes showed either unchanged or ≥2 line improvements of BCVA at last visit. There was no development of CMV retinitis in a fellow eye, or recurrence in a studied eye. Systemic complications such as neutropenia were not detected.Conclusions: Intravitreal ganciclovir injections combined with systemic anti-viral treatment is a good therapeutic option for treating CMV retinitis without HIV infection. Such treatment provided favorable visual outcomes, with minimal ocular and systemic complications.

Incidence of herpes zoster and its complications in Germany, 2005–2009

After introduction of a herpes zoster (HZ) vaccine in Germany in 2013, a potential recommendation by the German Standing Vaccination Committee is still pending. This study estimated data on the disease burden of HZ in Germany to extend the data basis for the decision process. A retrospective cohort study on data from 7 million statutory health insurance members from 2005 to 2009 was conducted. HZ cases were identified using ICD-10-codes. IRs of HZ and complications were estimated overall, by age, sex and immune status. The proportion of postherpetic neuralgia (PHN), hospitalizations, the diagnosing physician specialty and systemic antiviral therapy were assessed. Annual standardized IRs ranged between 5.3 and 5.5 per 1000 person-years (PY) between 2006 and 2009 with higher IRs in females. In 2009, 72.4% of HZ patients were without complications, while 15.5% suffered from nervous system involvement. The age-related increase was higher for HZ complications than for uncomplicated HZ. Immunocompromised patients suffered slightly more complications than immunocompetent patients. The PHN proportion increased to 15% in 2009 with a steady age-related increase. About 3% of HZ cases were hospitalized. Age-related increases of HZ complications and PHN suggest that particularly older patients might benefit from HZ vaccination.

Контагиозный моллюск в практике детского хирурга

В работе представлены сведения о контагиозном моллюске у детей. Контагиозный моллюск — доброкачественное заразное заболевание кожи, возникающее при контакте с больным человеком. Возбудителем является патогенный эпидермотропный вирус (Мolluscum contagiosum virus). В клинике детской хирургии им. проф. Н.Л. Куща за последние 15 лет (1997–2012 гг.) лечилось 116 детей по поводу контагиозного моллюска в возрасте от 8 месяцев до 16 лет. Лиц женского пола было 60 (51,7 %), мужского пола — 56 (48,3 %). Основную группу пациентов (около 70 %) составили больные в возрасте от 2 до 5 лет. Давность заболевания варьировала от нескольких недель до 4–6 месяцев. Диагноз заболевания устанавливали после изучения элементов сыпи с последующей патогистологической верификацией. При наличии нетипичных или сомнительных опухолеподобных образований диагноз контагиозного моллюска устанавливался только после гистологического исследования. В случаях типичных элементов сыпи диагноз контагиозного моллюска до оперативного лечения был выставлен у 102 детей. У остальных больных (14 пациентов) не исключалось также наличие папилломы, бородавки или дерматофибромы. Удаление контагиозного моллюска наблюдаемым детям проводилось методом диатермокоагуляции (электрокоагуляции) опухолеподобных узелков с тщательным удалением содержимого с последующей обработкой спирто-йодной настойкой. В обязательном порядке проводили патогистологическое исследование удаленных тканей моллюска. При единичных элементах использовали местный анестетик путем предварительного нанесения крема ЭМЛА (22 ребенка) за 30–40 минут до манипуляции. У оставшихся больных применяли общую кратковременную анестезию. Осложнений не наблюдали. Рецидивы заболевания имели место у 6 детей. После повторной диатермокоагуляции наступило выздоровление. Всем детям, независимо от места дальнейшего лечения, по показаниям назначались системная противовирусная терапия, поливитамины, пробиотики, иммуномодуляторы. Доказаны доступность и высокая эффективность лечения. Больного, у которого диагностирован контагиозный моллюск, изолируют от детского коллектива до полного выздоровления. Профилактика контагиозного моллюска заключается в своевременном выявлении инфекции и соблюдении правил личной гигиены. Выводы. Диатермокоагуляция контагиозного моллюска у детей является простым, доступным и эффективным методом лечения. Больные с контагиозным моллюском нуждаются в изоляции. После отпадения корочек в местах диатермокоагуляции дети могут посещать детский сад или школу.

A Clinical Study of Herpes Zoster Ophthalmicus

Background: Herpes Zoster Ophthalmicus(HZO) occurs from the reactivation of latent Varicella Zoster virus within the ophthalmic division of the Trigeminal nerve. Ophthalmic involvement has been considered the most important and potentially serious of all sites of Herpes Zoster. Objectives: 1.To study the modes of presentation and ocular manifestations of HZO. 2.To study the predisposing factors for the development of HZO. 3.To study the ocular complications of HZO after treatment with oral Acyclovir during a follow-up period of one year. Materials and Methods: This prospective clinical study was conducted with all patients who were clinically diagnosed to have HZO who attended the Outpatient Department of Ophthalmology. All the patients underwent a comprehensive ocular examination and were medically treated and followed up for one year. Results: 27 patients with HZO were studied. Advancing age was the most common predisposing factor. Acute neuralgia and skin lesions were the most common modes of presentation. Ocular involvement was seen in 16(59.25%) of the patients with HZO. Cornea was the most common ocular structure involved(62.5%). Conclusion: The potential ocular manifestations of HZO are numerous. Ocular complications were less frequent among patients who received prompt systemic antiviral therapy with oral Acyclovir started within 72 hours of skin rash. Among treated patients development of a serious inflammatory complication was associated with a delay in therapy.

Thymoma with immunodeficiency with multiple recurrent oral herpetic infections

Thymomas with immunodeficiency (formerly Good's syndrome) are a rare acquired disease of combined T- and B-cell immunodeficiency accompanying a thymoma. Recurrent opportunistic infections associated with disorders of both humoral and cell-mediated immunity frequently accompany this rare primary, adult-onset immunodeficiency. This is a report of a case of a thymoma with immunodeficiency in a 65-year-old male patient who developed recurrent oral herpetic infections. He consulted us about recurrent vesiculo-ulcerative lesions on his tongue, lower lip, and buccal mucosa. Results of laboratory examinations indicated hypogammaglobulinemia accompanied by diminished B cells in the peripheral blood, which is consistent with the characteristic features of a thymoma with immunodeficiency. After a diagnosis confirming herpes simplex virus infection, systemic antiviral therapy was administered, which was effective for his vesiculo-ulcerative lesions at follow-up. When an intractable infection accompanied by a thymoma is encountered, increased awareness about the clinical and immunological profiles of this primary immunodeficiency may help in its early diagnosis, thereby preventing mortality.

Ping-Pong-Transmission von Herpes-simplex-Virus 1 nach Hornhauttransplantation

Primary corneal graft failure (PCGF) after penetrating keratoplasty (PKP) despite good endothelial cell count of the transplant in organ culture rarely occurs in young patients. A herpes simplex virus type I (HSV-1) infection (transmission through the donor or reactivation by the patient) can lead to PCGF. We report on a 43-year-old man with pellucid marginal corneal degeneration and neurodermitis, who was underwent penetrating keratoplasty (PKP) on the left eye after acute corneal hydrops in both eyes. A repeat keratoplasty (re-PKP) had to be performed 15 days after the first PKP due to a primary graft failure. A re-re-PKP with simultaneous amniotic membrane transplantation (as a patch) and partial lateral tarsorrhaphy became necessary 4 months after the re-PKP due to melting on the edge of the graft with persistent epithelial defects. After intensive cooperation between ophthalmologists and pathologists the histopathological findings showed keratocytes which reacted immunohistochemically positive for HSV-1 antigens in the deep corneal stroma of both corneal grafts. The excised own cornea of the patient was histopathologically negative but the DNA-PCR for HSV-1 was weakly positive. After adequate topical and systemic antiviral therapy the third graft has remained clear for 12 months. In cases of PCGF after normal risk corneal transplantation the possibility of HSV infection should always be considered. After confirmation of the diagnosis with the help of the immunohistochemical tests and/or PCR, an adequate treatment with antiviral medication (acyclovir tablets 2 × 400mg for more than 1 year) should be administered to the patient after repeat PKP.

Acute retinal necrosis. 3 case reports

AbstractPurpose To present three case reports of acute retinal necrosis (ARN) syndrome and discuss the aspects of diagnosis, treatment and prognosis.Methods Retrospective analysis of clinical, laboratory, photographic and angiographic records of three immunocompetent patients with acute retinal necrosis syndrome.Results Two male 22 and 36 years old and one female 25 years old patients had typical clinical symptoms of ARN syndrome: sudden decrease of vision acuity, eye pain, multiple areas of peripheral retinal necrosis, occlusive vasculitis, opticopathia, anterior uveitis and vitritis. Serum Ig G antiviral (VZV, HSV, CMV) titers were the basis for the etiological diagnosis. After applying systemic antiviral and steroid therapy, a rapid improvement of symptoms with the development of pigmentation in the areas of retinal whitening was observed in all patients. Retinal detachment occurred in 2 male patients and was successfully treated.Conclusion Acute retinal necrosis syndrome is one of the vision threatening diseases for immunocompetent patients with poor prognosis. Early diagnosis and urgent antiviral therapy is therefore of vital importance for visual outcomes. Long term follow‐up is necessary due to high risk of retinal detachment.

Prevention and treatment of oral lesion in AIDS by Chinese herb gargle

Objective To study the effects of self-made Chinese sherbal gargle on AIDS related oral lesion.Methods 353 hospitalized AIDS patients from June 2007 to December 2009 were divided randomly into the experimental group(179 patients)and the control group(174 patients).ALL the patients were treated with systemic anti-viral therapy while the experimental group was mouthwashed by self-made herbal gargle and the control group with normal saline solution.The incidence of new oral lesion and the changes of the originM lesion were observed.Results The incidence of new oral lesion in the experimental group was obviously lower than that of the control group.The cure rate and effective rate of original oral lesion were much higher than the control group.Conclusions Self-made herbal gargle shows good effect in preventing and treating the AIDS related oral lesion. Key words: AIDS; Oral lesion; Chinese herbs gargle

Approach to recurrent CMV disease and antiviral resistance

We appreciate the opportunity to further discuss our recent report on recurrent cytomegalovirus (CMV) retinitis in a non-HIV patient [1], in particular to respond to the interest and letter from Dr. Wiwanitkit, who asked us to address our approach to recurrent CMV disease and antiviral resistance. Presently, our patient remains disease-free, without evidence of retinitis or viremia. Favorably, she has not required further immunosuppression for the past 25 months. Treatment with high-dose (∼5,000–6,000 mcg/dose) GCV injections provided adequate local concentrations to inhibit/ control ocular infection. We suspect that lack of recurrent CMV disease is indicative of development of CMV-specific immunity. Our patient, in particular, experienced primary CMV infection with a high viral load during a period of intense immunodeficiency. Systemic antiviral therapy failed to suppress viremia and likely contributed to resistance. Viral clearance paralleled the rise in CD4 T lymphocytes [1]. Although CD4 T lymphocyte recovery suggests immune reconstitution, CD4 count recovery is not always associated with development of CMV-specific immunity, as demonstrated in an AIDS patient by Johnson et al. [2] and noted by Dr. Wiwanitkit. Among HIV patients, the best strategy to prevent CMV disease is early HAART, which has been associated with a marked decline in the incidence of CMV in this population. CMV drug resistance today primarily impacts solid-organ transplant recipients. We agree with Dr. Wiwanitkit that optimal treatment of drug-resistant CMV disease is limited and new agents are needed. Our case suggests that suprapharmacologic dosing of antivirals can be effective for treatment of retinitis due to drug-resistant CMV.

Klinik des Zoster Ophthalmicus

Zoster ophthalmicus (ZO) is a common disease, in particular in elderly and immunocompromised patients. In addition to the characteristic dermal lesions and to the postherpetic neuralgia, the clinical appearance may include very different forms of eye involvement. This article reviews the clinical features of ZO as well as the typical eye complications and therapy. 50 % of ZO patients have eye involvement. The acute phase of ZO is characterised by lid exanthema, conjunctivitis and epithelial keratitis (up to 65 %). In the late phase, stromal keratitis (up to 25 %), anterior uveitis (up to 50 %), and acute retinal necrosis (ARN) may occur. Typical complications are eyelid malposition, neurotrophic keratopathy (up to 25 %) and glaucoma. The diagnosis is usually based on the characteristic dermal lesions. In atypical cases, immunohistochemistry and PCR are tools for virus detection. All ZO patients should immediately receive systemic antiviral therapy. Corticosteroid therapy is essential for the management of the concomitant immune reaction that is relevant for the long-term prognosis, especially in stromal keratitis, uveitis, scleritis and ARN. All patients should receive systemic antiviral treatment to avoid complications and visual impairment. With appropriate medical and surgical therapy the prognosis is usually good. Postherpetic neuralgia is often the major issue in the later course. For the prevention of ZO and its complications, a vaccination is useful.

Recurrent CMV retinitis in a non-HIV patient with drug-resistant CMV

We report a case of recurrent cytomegalovirus (CMV) retinitis in an HIV-negative patient with CD4+ T lymphocytopenia. Case report. A 41-year-old HIV-negative woman with a history of systemic lupus erythematosus, idiopathic thrombocytopenic purpura requiring splenectomy, and diabetes presented with primary CMV infection, high-grade viremia, CMV pneumonia followed by CMV retinitis (CMVR) and a CD4+ T lymphocyte (CD4) count of 12 cells/mm(3) after therapy with rituximab, prednisone, and methotrexate. Persistent CMV viremia led to genotypic analysis of the circulating virus, which revealed UL97 and UL54 mutations known to be associated with resistance to ganciclovir (GCV) and cidofovir. CMV clearance from the bloodstream followed systemic antiviral therapy and recovery of CD4 cell count. However, CMVR recurred multiple times despite GCV implants, systemic valganciclovir, intravitreal GCV injections, and persistent CD4 counts greater than 100 cells/mm(3). Recurrent episodes of CMVR responded to multiple high dose intravitreal GCV injections (5000-6000 micrograms) and recovery of CD4 cell counts to greater than 200 cells/mm(3). This case demonstrates that recurrent CMVR occurs in HIV-negative patients at CD4 cell counts thought to be protective in HIV patients, and suggests that an ineffective local immune response to retinal infection combined with CMV drug resistance may have been important factors leading to recurrent disease in this patient. Treatment producing high local concentrations of GCV may be effective therapy for CMV retinitis due to GCV-resistant virus.