Intra-host diversity of drug-resistant cytomegalovirus: A case report of cytomegalovirus infection after allogeneic hematopoietic cell transplantation.

Cytomegalovirus (CMV) is a major infectious agent causing severe complications in allogeneic hematopoietic cell transplantation (HCT) recipients, thereby warranting the need for aggressive preemptive or targeted antiviral therapy. However, prolonged or repeated use of antiviral agents, such as ganciclovir (GCV), foscarnet (FOS), and cidofovir (CDV), can result in drug-resistant CMV infection, posing challenges to successful outcomes. Here, we report a case of a patient with acute myeloid leukemia and drug-resistant CMV infection who presented with persistent CMV DNAemia, colitis, pneumonia, and encephalitis. An intra-host diversity of UL97 and UL54 mutations were detected through the genotypic resistance testing conducted on two blood samples (D+199 and D+224) and a cerebrospinal fluid (CSF) specimen (D+260) collected from the patient. UL97 L595W/L595F and L595W mutations were detected in the blood and CSF samples, respectively, that conferred GCV resistance. UL54 F412L mutation detected in all three samples conferred GCV/CDV resistance. However, the V787L mutation of UL54, conferring GCV/FOS resistance, was observed only in the D+224 blood sample. Despite combination therapy with FOS and high dose GCV and adjunctive therapy with leflunomide, the patient died from CMV infection and multiple organ failure on D+279. Further data on resistant mutations and intra-host diversity of CMV should be accumulated to elucidate the antiviral resistance and related outcomes.

Detection of Pre-clinical Involvement of the Second Eye in Viral Acute Retinal Necrosis Using Optical Coherence Tomography.

PURPOSE: To report the detection of retinitis in the second eye of a patient with viral acute retinal necrosis (ARN), before the appearance of clinical change, using swept-source optical coherence tomography. RESULTS: A 63 year-old male developed right-sided varicella-zoster virus (VZV) ARN, confirmed with aqueous sampling. High-dose intravenous aciclovir caused renal impairment and was suspended for two-days. One day later, left eye macular SS-OCT revealed focal retinal thickening and disruption of retinal architecture without clinically detectable retinitis. The patient was asymptomatic. Aqueous sampling was VZV PCR positive. He received bilateral foscarnet injections and renal adjusted dose of aciclovir. The left OCT signs improved with full restoration of retinal layers. CONCLUSIONS: We report for the first time the use of OCT to detect pre-clinical second eye retinitis during ARN. Prompt diagnosis and combined systemic and intensive local antiviral therapy resulted in a favourable structural and functional outcome.

ACUTE RETINAL NECROSIS: Difference in Outcome by Viral Type and Options for Antiviral Therapy.

PURPOSE: To investigate differences in outcomes of acute retinal necrosis with confirmed viral polymerase chain reaction between viral types and highlight different treatment options. METHODS: The study evaluated 22 eyes in 18 patients of polymerase chain reaction-positive acute retinal necrosis at the University of Pittsburgh Medical Center from 2007 to 2018. Outcome measures included final visual acuity, treatment paradigms, and retinal detachment rate. RESULTS: Eight eyes were polymerase chain reaction-positive for varicella zoster virus, two eyes for herpes simplex virus Type 1 (HSV-1), and 12 eyes for herpes simplex virus Type 2 (HSV-2). Final Snellen best-corrected visual acuity averaged 20/51 for varicella zoster virus, 20/25 for HSV-1, and 20/814 for HSV-2. Retinal detachment occurred in 2 (25%) of varicella zoster virus eyes and 8 (75%) of HSV-2 eyes. One eye with HSV-1 and three eyes with HSV-2 received cidofovir for treatment of refractory retinitis. CONCLUSION: Acute retinal necrosis secondary to HSV-2 tended to have persistent active retinitis with a higher rate of retinal detachment despite similar treatment protocols, suggesting that in some cases combination intravenous acyclovir and adjuvant intravitreal foscarnet injections are not sufficient. Despite the risk of renal toxicity, intravenous cidofovir may be a consideration in select patients.

Management of Ganciclovir Resistant Cytomegalovirus Retinitis in a Solid Organ Transplant Recipient: A Review of Current Evidence and Treatment Approaches.

Purpose: Cytomegalovirus retinitis (CMVR) is a serious and potentially sight-threatening infection in immunocompromised individuals. Strategies for the management of drug-resistant CMVR are described. Methods: A case of severe bilateral CMVR in a single lung transplant patient, with UL97 mutation conferring ganciclovir-resistance, is presented. Treatment with standard antiviral agent and adjuvant leflunomide, immunosuppression modifications (calcineurin inhibitors and corticosteroid), intravitreal antiviral therapy and novel use of CMV-immunoglobulin is described. A literature review to support drug-resistant CMVR management is presented. Results: Severe and progressive CMV retinitis was refractory to intravitreal foscarnet and systemic leflunomide. Drug-toxicity restricted systemic antiviral therapy options. The use of combined leflunomide and CMV-immunoglobulins, in the absence of viremia, has not been previously reported. Loss of ganciclovir-resistance was eventually observed permitting successful treatment with systemic and intravitreal ganciclovir. Conclusions: Drug-resistant CMVR is a complex clinical challenge. Multiple systemic and local treatment strategies may be necessary but toxicity, resistance, and co-morbidities may severely restrict available options.

Acute retinal necrosis in a patient with remote severe herpes simplex encephalitis.

A 60-year-old man with a history of severe herpes simplex virus type 1 (HSV-1) encephalitis 2 years prior presented with acute onset of visual loss in the left eye. Dilated funduscopic examination showed retinitis and occlusive vasculitis with retinal necrosis. PCR of the vitreous fluid was positive for HSV-1, and he was diagnosed with acute retinal necrosis (ARN) due to HSV-1. The patient was treated with intravenous acyclovir and intravitreous foscarnet for 2 weeks, followed by high dose oral valacyclovir for 2 weeks. He was subsequently placed on planned life-long suppressive valacyclovir. His case demonstrates that acute visual loss concomitant with or subsequent to HSV-1 encephalitis warrants suspicion of ARN. Prompt therapy with effective antiviral medication is necessary to reduce the risk of sight-threatening complications. Chronic suppression with oral antiviral therapy after ARN is recommended to prevent involvement of the contralateral eye, though there is no consensus on the duration and dosage of antivirals.

Resistant Cytomegalovirus Infection After Renal Transplantation: Literature Review.

BACKGROUND: Resistant cytomegalovirus (R-CMV) is an emerging problem in the renal transplantation population. The most frequent CMVs are high-resistance mutations (UL97 gene). METHODS: We describe our experience in management of R-CMV after renal transplant at our center (2012-2016). RESULTS: We encountered 3 cases of R-CMV infection after renal transplant (all primary infections). All 3 patients received induction therapy with corticosteroids, tacrolimus, and mycophenolate mofetil. The first patient (basiliximab induction, preemptive CMV) developed CMV replication on day +53, which responded poorly both to standard-dose valganciclovir (vGCV) and high-dose ganciclovir (GCV) (creatinine clearance [CrCl] >70 mL/min; vGCV 900 mg twice daily for 50 days and GCV 7.5 mg/kg twice daily for 8 days). Hematologic toxicity occurred. The R-CMV test was positive and foscarnet (FOS) was initiated (90 mg/kg twice daily for 21 days). The second patient presented CMV infection (day +30, thymoglobulin induction, CMV prophylaxis), which was not controlled with the high dose (CrCl 23 mL/min; GCV 3.5 mg/kg twice daily and vGCV 900 mg twice daily), resulting in severe neutropenia. R-CMV was detected and FOS initiated (FOS 50 mg/kg twice daily for 7 days and 50 mg/kg every 2 days for 13 days). The third patient's infection occurred on day +22 (basiliximab induction, preemptive CMV). Standard-dose vGCV was uneffective (CrCl >70 mL/min, vGCV 900 mg twice daily) and it did not respond to the high dose (GCV 7.5 mg/kg twice daily and vGCV 2700 mg/d). Moderate hematologic toxicity occurred. R-CMV was diagnosed and FOS treatment begun (FOS 70 mg/kg per day for 2 weeks). CONCLUSIONS: Resistant CMV infection may be severe due to viral infection and side effects of high-dose antiviral treatment. We presented 3 cases requiring the use of FOS in the absence of response or toxic effects from the usual treatment, with an optimal sustained response (temporary in case 2) and without serious side effects.

[Acyclovir-resistant perineal HSV infection revealing chronic lymphoid leukaemia]. / Herpès chronique périnéal résistant à l'aciclovir révélateur d'une leucémie lymphoïde chronique.

BACKGROUND: Chronic HSV infection is a cause of chronic perineal ulcerations. We report a case of a chronic and refractory HSV infection revealing chronic lymphoid leukaemia. PATIENTS AND METHODS: An 85-year-old woman with an 8-month history of chronic perineal ulcerations was referred to our dermatology department. She had no previous medical history of herpes infection. Skin biopsies ruled out carcinoma but were consistent with HSV infection. A local swab was positive for HSV2. Treatment with valaciclovir and intravenous acyclovir (ACV) at the recommended doses was ineffective. Laboratory tests revealed type-B chronic lymphoid leukaemia. Molecular biology studies confirmed the presence of ACV-resistant HSV via decreased thymidine kinase activity (stop codon: M183stop). Foscarnet was administered for a period of 3 weeks with almost complete healing of the ulcerations. Treatment was stopped prematurely due to acute renal insufficiency and the remaining lesions were treated using imiquimod cream. Valaciclovir was prescribed to prevent further episodes. The condition recurred a mere 11 months later. DISCUSSION: The prevalence of ACV-resistant HSV is 0.32 % in immunocompetent patients and 3.5 % in immunocompromised patients. Insufficient dosing regimens or prolonged treatment with TK inhibitors result in the local selection of pre-existing mutant HSV viruses. Foscarnet, a DNA polymerase inhibitor, is the treatment of choice in HSV-resistant infections. ACV-resistant HSV is less virulent and replicates less, with reactivations being mainly due to wild-type HSV latent in the neural ganglia. Valaciclovir can be used as a preventive treatment. To our knowledge, this is the first case of ACV-resistant HSV infection revealing chronic lymphoid leukaemia. CONCLUSION: Chronic perineal ulcerations can be the first manifestation of immunodeficiency seen for example with haematological diseases. In the event of clinical resistance of an HSV infection to recommended thymidine kinase inhibitor regimens, the use of foscarnet should be considered.

Epidemiology and Outcome of Ganciclovir-Resistant Cytomegalovirus Infection After Solid Organ Transplantation: A Single Transplant Center Experience in Thailand.

BACKGROUND: Data on drug-resistant cytomegalovirus (CMV) infection in solid organ transplantation (SOT) are not often reported from resource-limited settings. We aimed to investigate the epidemiology and outcomes of this infection in SOT recipients at our institution. METHODS: This was a retrospective study conducted from January 2012 to May 2015. We included all SOT recipients who were suspected for drug-resistant CMV infection. Genotypic assay for UL97 gene mutation was analyzed by real-time polymerase chain reaction. Patients were reviewed for demographic data, clinical presentation, virologic data, treatment, and outcomes. RESULTS: The population consisted of 18 (12 kidney, 6 liver) SOT recipients with a median age of 20 years (interquartile range [IQR], 1-49); 44% were male. Anti-CMV resistance testing was analyzed at a median time of 23 days (IQR, 14-33) after initiation of anti-CMV therapy with a median CMV load of log 3.79 copies/mL (IQR, 3.37-4.58). During a median period of 2 years (IQR, 1-3), 6 SOT recipients were identified with UL97 gene mutation in codon 460, conferring ganciclovir (GCV) resistance. Patients with UL97 gene mutation had a longer mean duration of CMV DNAemia compared with those without mutation (263 vs 107 days; P = .04). All patients received high-dose GCV. Two patients received foscarnet and cidofovir. Two patients died (non-CMV-related), and 4 patients developed opportunistic infections other than CMV. CONCLUSIONS: GCV-resistant CMV infection in SOT recipients is an emerging clinical problem in resource-limited country. Those with UL97 mutation CMV infection have prolonged duration of CMV DNAemia. Clinicians should be aware of this condition when caring for SOT recipients.

Recurrent Herpes Labialis in Adults: New Tricks for an Old Dog.

Herpes labialis remains a common worldwide affliction. Recent advances in understanding the basic pathogenesis have led to new therapeutic intervention, both on-label and off-label. Aside from reducing the duration and symptomatology of acute outbreaks, another goal of treatment is to decrease the frequency of future episodes. Oral and topical acyclovir and its analogues are the mainstay of both chronic suppressive and episodic therapy. A new muco-adhesive formulation of acyclovir provides a decrease in outbreaks, probably due to a diminution of herpesvirus load in all reservoir sites. Acyclovir-resistant strains are rare in immunocompetent hosts; parenteral foscarnet and cidofovir are administered in this situation. Parenteral acyclovir is the drug of choice for eczema herpeticum, which may begin as herpes labialis in an atopic dermatitis patient. Thermotherapy may be beneficial, and a certified device to deliver heat is available outside the United States.

J Drugs Dermatol. 2017;16(3 Suppl):s49-53.

Adjuvant and salvage therapy with leflunomide for recalcitrant cytomegalovirus infections in hematopoietic cell transplantation recipients: A case series.

Cytomegalovirus (CMV) reactivation is a clinically significant complication in hematopoietic stem cell transplant (HCT) recipients. Alternative therapy for multidrug-resistant CMV is limited and often fails. Leflunomide has been used to treat resistant CMV infections, however, data on efficacy, safety, and guidance for therapeutic drug level monitoring are lacking. In this report, we describe 3 HCT recipients with multi-drug resistant CMV infections who received leflunomide as adjuvant and salvage therapy. The therapeutic effect of leflunomide as an anti-CMV agent based on virologic responses and therapeutic drug monitoring were evaluated.

Acute myelitis by human herpes virus 7 in an HIV-infected patient.

BACKGROUND: HHV7 reactivation has been occasionally reported as a cause of encephalitis or myelitis in transplant recipients, but to our knowledge it has never been associated with neurological disease in HIV-infected patients. We report a case of acute myelitis in an HIV-infected patient, with sustained HHV-7 DNA amplification in cerebrospinal fluid (CSF) and a favourable response to foscarnet. CASE REPORT: A 40 year-old man with HIV infection was admitted with asymmetric hypoesthesia in legs and paraparesis. He was receiving treatment with efavirenz, emtricitabine and tenofovir, his CD4 count was 580/mm3 and HIV viral load was undetectable. Magnetic resonance imaging showed a focal central hyperintensity on T2 and STIR sequences, on the torathic spinal cord, with slight enhancement after intravenous gadolinium. All microbiological studies were negative except for HHV-7 DNA amplification in CSF. With a diagnosis of idiopathic transverse myelitis, treatment with high-dose intravenous methylprednisolone was initiated. However, paraparesis continued worsening, and a second CSF obtained 12 days after the first one resulted again in HHV-7 amplification. RESULTS: The patient was treated with a 2 week course of foscarnet, and a rapid neurological improvement was noted. After treatment, PCR for HHV-7 in CSF was negative. Neurological exam was normal one month after treatment initiation. CONCLUSION: HHV-7 reactivation may cause neurological disease in patients with HIV infection. Foscarnet is an effective treatment in HHV-7 associated myelitis.

[Systemic cytomegalovirus infection: changes in serum calcium and magnesium levels with foscarnet treatment]. / Infección sistémica por citomegalovirus: influencia del tratamiento con foscarnet en los niveles plasmáticos de calcio y magnesio.

Cytomegalovirus infection is common in cardiac transplant patients. Foscarnet is used, with limited evidence, as second-line treatment after ganciclovir failure in these patients. We describe the case of a paediatric cardiac transplant patient who developed electrolyte disturbances during foscarnet treatment for cytomegalovirus infection. The infection resolved after 6 weeks of treatment. Low ionized calcium and magnesium levels were observed during the drug infusion, which were treated with supplements. The serum levels reverted to normal after drug withdrawal.

Presumed cytomegalovirus-associated retrobulbar optic neuritis in a patient after allogeneic stem cell transplantation.

A case of cytomegalovirus (CMV)-associated bilateral retrobulbar optic neuritis (ON) following haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is reported. Abrupt onset of bilateral decreased vision occurred in a 33-year-old man 7 months after haplo-HSCT. His cerebrospinal fluid (CSF) demonstrated pleocytosis with an absence of leukemic cells. CMV DNA was detected in his blood and CSF sample. Neither encephalopathy nor retinopathy was found in this patient. He was diagnosed with bilateral retrobulbar ON. Although he was given enough antiviral treatment against CMV and immunosuppression with high-dose methylprednisolone, the patient's vision showed no improvement, and he has almost total bilateral blindness. This is the first report, to our knowledge, of CMV-associated bilateral retrobulbar ON in allogeneic stem cell transplantation.

Treatment of HIV-related primary central nervous system lymphoma with AZT high dose, HAART, interleukin-2 and foscarnet in three patients.

PURPOSE: Combined immunomodulatory and antiviral treatment was administered to three patients with newly diagnosed HIV-associated primary central nervous system lymphoma (PCNSL) in an attempt to improve outcomes. PATIENTS AND METHODS: Three patients from our institution who were recently diagnosed with HIV-associated PCNSL received intravenous azidothymidine (AZT) 1.6 gr. bid for two weeks, followed by oral AZT 250mg bid from day 15. In addition, complementary highly active antiretroviral therapy (HAART) with a second nucleoside reverse transcriptase inhibitor (NRTI) plus one protease inhibitor (PI) and interleukin 2 (IL-2) subcutaneously 2 million units twice daily (bid) plus foscarnet 90mg/kg bid were administered on days 1-14. One patient received anti-Epstein-Barr virus (EBV)-maintenance therapy with ganciclovir, followed by cidofovir. RESULTS: All patients experienced progressive disease while on induction therapy, and switched early to whole-brain radiation therapy (WBRT) as second line-treatment. No grade 3 or 4 toxicities were observed. Two patients died on days 50 and 166 respectively due to progressive disease. The third patient with histo?logically proven lymphoproliferation and only suspected PCNSL remained alive at 53 months. He was on HAART and remained clinically and neurologically stable. CONCLUSION: Although IL-2, HAART, high-dose AZT and foscarnet are used for other HIV-related conditions, they did not demonstrate benefit in lymphoma remission for 2 HIV- associated PCNSL patients. The third patient went into delayed remission after additional radiotherapy and was in good clinical and neurological health status over 53 months after diagnosis.

Foscarnet salvage therapy for acyclovir-resistant varicella zoster: report of a novel thymidine kinase mutation and review of the literature.

The authors describe an acyclovir-resistant varicella zoster virus infection in a pediatric patient after hematopoietic stem cell transplant, the use of foscarnet as salvage therapy, and review the literature to clarify the pediatric experience with foscarnet in this setting. A novel thymidine kinase mutation is described, along with a new phenotypic assay for characterizing acyclovir resistance in varicella zoster virus.

Long-term foscarnet therapy remodels thymidine analogue mutations and alters resistance to zidovudine and lamivudine in HIV-1.

OBJECTIVE: To study the evolution of multi-drug-resistant HIV-1 in treatment-experienced patients receiving foscarnet (PFA) as part of salvage therapy and to investigate the virological consequences of emerging mutations. METHODS: Genotypic and phenotypic resistance tests were performed on plasma viruses from seven patients at baseline and during treatment with PFA. The phenotypic effects of mutations suspected to be associated with PFA resistance were evaluated by site-directed mutagenesis of wild-type or thymidine analogue mutations (TAM)-carrying pNL4-3. Reversion of single mutations was performed in a patient-derived recombinant clone. RESULTS: Baseline multi-drug-resistant isolates exhibited hypersusceptibility to PFA. In two patients who received > 12 months of PFA treatment, a novel mutation pattern including K70G, V75T, K219R and L228R emerged. These viruses had 3-6-fold resistance to PFA, a 2-20-fold decrease in resistance to zidovudine compared to baseline, and 14-39-fold resistance to lamivudine, in the absence of M184V. In wild-type clones mutations K70G and V75T induced moderate PFA resistance. In the case of TAMs, combinations of > or = 3 mutations (K70G+K219R+L228R+/-V75T) induced PFA resistance and decreased zidovudine resistance 3-13-fold. These mutants exhibited high-level lamivudine resistance (>20-fold) without mutation M184V. Reversion of K70G --> R and K219R --> E in a patient-derived clone confirmed the contribution of individual mutations and the negative association between PFA resistance and zidovudine resistance. CONCLUSIONS: In the context of multiple TAMs, hypersusceptibility to PFA was observed and a novel pattern of resistance, including alternative amino acid substitutions at TAM loci, emerged. This mutational pattern was associated with decreases in zidovudine resistance and surprisingly high-level lamivudine resistance.

Is combination antiviral therapy for CMV superior to monotherapy?

BACKGROUND: Many clinicians are under the impression that the combination of ganciclovir (GCV) and foscarnet is synergistic versus cytomegalovirus (CMV) and/or that combination therapy might prevent the emergence of resistance to one or both antivirals. The combination is frequently used when resistance to either drug is suspected. OBJECTIVE: To review in vitro and clinical data regarding the activity of ganciclovir plus foscarnet and evidence of synergy between the two drugs. STUDY DESIGN: We reviewed two in vitro studies of synergy between ganciclovir and foscarnet followed by reviewing all clinical studies utilizing series of patients. RESULTS: The combination of ganciclovir and foscarnet was synergistic against three clinical isolates, the Towne strain and one laboratory derived strain moderately resistant to GCV but synergy was not demonstrated against laboratory derived strains highly resistant to GCV or foscarnet. AD169, susceptible to both drugs, was not inhibited synergistically by the combination in one study but was in the second study. In the only carefully controlled in vivo study of combination versus monotherapy for GCV susceptible viremia superiority of the combination was not demonstrated. In treating clinically resistant CMV retinitis, the combination was superior to continued or alternative monotherapy. CONCLUSION: There is suggestive but inconclusive evidence of in vitro synergy for the combination of GCV and foscarnet versus CMV with very limited data versus GCV resistant virus. The in vivo data for synergy is even less convincing. Additional in vitro and in vivo data is needed, especially to prevent or treat CMV resistance.

A phase II, double-masked, randomized, placebo-controlled evaluation of a human monoclonal anti-Cytomegalovirus antibody (MSL-109) in combination with standard therapy versus standard therapy alone in the treatment of AIDS patients with Cytomegalovirus retinitis.

ACTG 266 was designed as a randomized study to evaluate two doses of the human monoclonal antibody directed against CMV gH (MSL-109) versus placebo, each in combination with standard antiviral therapy for the treatment of newly diagnosed Cytomegalovirus (CMV) retinitis in AIDS patients. A total of 82 subjects were enrolled and received either placebo (n = 28), or MSL-109 at 15 mg (n = 26) or 60 mg (n = 28) every 2 weeks until disease progression was diagnosed. The primary endpoint, disease progression, was determined by masked reading of retinal photographs taken every 4 weeks read by a single investigator. The median time to progression was 8.0, 8.3, and 12.1 weeks in the placebo, MSL-109 15mg and MSL-109 60 mg cohorts, respectively (P = 0.087, placebo versus 60 mg cohort). There were 22 deaths during the study period (9, 9, and 4 in the placebo, MSL-109 15 mg and MSL-109 60 mg cohorts, respectively (P = 0.0058, placebo versus 60 mg cohort)). MSL-109 was well tolerated with no significant adverse events attributable to study medication. The unexplained survival advantage in the higher dose cohort was discordant with the findings of the parallel Studies of Ocular Complications of AIDS Research Group (SOCA)-Monoclonal Anti-CMV Retinitis Trial (MACRT), which was prematurely halted because of increased mortality in subjects treated with high-dose MSL-109, recognizing that A266 enrolled subjects with newly diagnosed, whereas the MACRT enrolled subjects with relapsed, CMV retinitis.

Clinical characteristics of acute HSV-2 retinal necrosis.

PURPOSE: To report the clinical features and evaluate the visual outcome of eleven cases of herpes simplex virus-2 (HSV-2) related acute retinal necrosis syndrome (ARN). DESIGN: Retrospective interventional case series. METHODS: Twelve eyes of eleven patients from two European centers, diagnosed with HSV-2 related acute retinal necrosis syndrome were retrospectively reviewed. Herpes simplex virus-2 DNA was detected by polymerase chain reaction in intraocular fluids (aqueous and/or vitreous). Findings at initial examination, clinical evolution with antiviral therapy, complications and final visual acuity were evaluated. RESULTS: Herpes simplex virus-2 DNA was detected in all cases. No sample was positive for more than one virus. The mean age of disease in the first eye was 36 years (ranged from 10 to 57 years). Five patients were women and six were men. All patients were immunocompetent. Previous medical history included neonatal herpes (n = 1), previous ARN (n = 3), trauma (n = 1) and systemic corticosteroid administration before occurrence of ARN (n = 3). Preexisting pigmented chorioretinal scars were found in three cases. Patients were treated with high dose intravenous acyclovir or foscarnet +/- intravitreal ganciclovir +/- interferon. The mean follow-up was 14.5 months (from 5 to 22 months). At the end of the follow-up period, five eyes (41.7%) showed improvement of visual acuity of two or more lines. Final visual acuity was 20/60 or better in four eyes (33.3%), 20/400 or better in four eyes (33.3%) and less than 20/400 in four eyes. CONCLUSION: History of neonatal herpes, triggering events such as neurosurgery, periocular trauma, high-dose corticosteroids, and chorioretinal scars suggest that HSV-2 retinitis reflects reactivation of HSV-2 infection.