Search

Purpose : To assess the immune status of acute retinal necrosis (ARN) patients and to investigate the immune cell types involved in the immunopathogenesis. Methods : Peripheral blood and intraocular fluid were collected from 17 ARN patients and 9 control subjects. The Percentage of immune cells was measured using flow cytometry, levels of complement and antibodies were determined by rate nephelometry, and cytokine levels in the serum and aqueous humor (AH) were detected using cytokine quantitative chips. Data were analyzed using SPSS 23.0. p < .05 was considered statistically significant. Results : Proportion of T-helper 17 cells ( p = .034) in serum and concentrations of multiple cytokines associated with Th17 cells (IL-6, IL-17, IL-17 F, IL-21, IL-22) in AH and serum were elevated of ARN patients. Conclusion : Th17 cells appeared to participate in the development of ARN. We found inflammatory cytokines and cells were elevated in the serum and AH of ARN patients.

Objective: To assess and understand the prevalence and clinical presentation of ocular morbidity in patients suffering from tuberculosis and compare it with ocular involvement in patients coinfected with tuberculosis and HIV AIDS., Materials and Methods: This was a non-comparative, observational, cross sectional study done on 580 patients, who were diagnosed cases of tuberculosis, pulmonary or extrapulmonary, on or off treatment, visiting the Ophthalmology OPD, Tuberculosis OPD and ART Centre of the institute in the period from March 2015 to March 2018, screened for ocular morbidity., Results: Out of 580, 408 patients had only tuberculosis and 172 had tuberculosis with HIV AIDS. 108 patients were found to have ocular involvement (18.6%) out of which 63 were males and 45 were females. The prevalence of ocular morbidity in patients with only tuberculosis was found to be 16.4% and in those having both tuberculosis and HIV AIDS was found to be 23.8%., Conclusion: Our study concludes that posterior uveitis, pan uveitis, periphlebitis and vitritis are the most common ocular manifestations in tuberculosis. In patients with both tuberculosis and HIV most common ocular findings included vitritis and herpes zoster ophthalmicus. Our study also concludes that lower CD4 counts (less than 200) in HIV AIDS patient is significantly associated with ocular involvement., (Copyright © 2019 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Herpes simplex virus, varicella zoster virus, human cytomegalovirus, and rubella virus are the most common causes of virus-induced anterior uveitis. They can present in a variety of entities not only with typical but also overlapping clinical characteristics. These viral infections are commonly associated with ocular infiltration of T cells and B/plasma cells, and expression of cytokines and chemokines typical of a proinflammatory immune response. The infections differ in that the herpes viruses cause an acute lytic infection and inflammation, whereas rubella virus is a chronic low-grade infection with slowly progressing immunopathological responses. The outcome of an intraocular viral infection may largely be guided by the characteristics of the virus, which subsequently dictates the severity and type of the immune response, and the host immune status.

Background: Herpes zoster ophthalmicus affects the eye and vision, and is caused by the reactivation of the varicella zoster virus in the distribution of the first division of the trigeminal nerve. An aggressive management of acute herpes zoster ophthalmicus with systemic antiviral medication is generally recommended as the standard first-line treatment for herpes zoster ophthalmicus infections. Both acyclovir and its prodrug valacyclovir are medications that are approved for the systemic treatment of herpes zoster. Although it is known that valacyclovir has an improved bioavailability and steadier plasma concentration, it is currently unclear as to whether this leads to better treatment results and less ocular complications., Objectives: To assess the effects of valacyclovir versus acyclovir for the systemic antiviral treatment of herpes zoster ophthalmicus in immunocompetent patients., Search Methods: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register; 2016, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2016), Embase (January 1980 to June 2016), Web of Science Conference Proceedings Citation Index-Science (CPCI-S; January 1990 to June 2016), BIOSIS Previews (January 1969 to June 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 13 June 2016., Selection Criteria: We considered all randomised controlled trials (RCTs) in which systemic valacyclovir was compared to systemic acyclovir medication for treatment of herpes zoster ophthalmicus. There were no language restrictions., Data Collection and Analysis: Two review authors independently selected trials, evaluated the risk of bias in included trials, and extracted and analysed data. We did not conduct a meta-analysis, as only one study was included. We assessed the certainty of the evidence for the selected outcomes using the GRADE approach., Main Results: One study fulfilled the inclusion criteria. In this multicentre, randomised double-masked study carried out in France, 110 immunocompetent people with herpes zoster ophthalmicus, diagnosed within 72 hours of skin eruption, were treated, with 56 participants allocated to the valacyclovir group and 54 to the acyclovir group. The study was poorly reported and we judged it to be unclear risk of bias for most domains.Persistent ocular lesions after 6 months were observed in 2/56 people in the valacyclovir group compared with 1/54 people in the acyclovir group (risk ratio (RR) 1.93 (95% CI 0.18 to 20.65); very low certainty evidence. Dendritic ulcer appeared in 3/56 patients treated with valacyclovir, while 1/54 suffered in the acyclovir group (RR 2.89; 95% confidence interval (CI) 0.31 to 26.96); very low certainty evidence), uveitis in 7/56 people in the valacyclovir group compared with 9/54 in the acyclovir group (RR 0.96; 95% CI 0.36 to 2.57); very low certainty evidence). Similarly, there was uncertainty as to the comparative effects of these two treatments on post-herpetic pain, and side effects (vomiting, eyelid or facial edema, disseminated zoster). Due to concerns about imprecision (small number of events and large confidence intervals) and study limitations, the certainty of evidence using the GRADE approach was rated as low to very low for the use of valacyclovir compared to acyclovir., Authors' Conclusions: This review included data from only one study, which had methodological limitations. As such, our results indicated uncertainty of the relative benefits and harms of valacyclovir over acyclovir in herpes zoster ophthalmicus, despite its widespread use for this condition. Further well-designed and adequately powered trials are needed. These trials should include outcomes important to patients, including compliance.

We report three patients with ophthalmic herpes zoster (HZ) manifestations on the background diagnosis of multiple myeloma (MM). It seems that immunocompromised status has caused reactivation of the varicella zoster virus (VZV) producing a well-characterised neurological syndrome and subsequent postherpetic neuralgia in two patients. One patient experienced lymphocytic leptomeningitis resulting in unilateral optic neuritis. All patients received similar myeloma disease-specific treatment prior to HZ reactivation. All patients were treated with thalidomide and steroids, and they thereafter underwent autologous stem cell transplantation. Prior to HZ reactivation they received new immunomodulatory drugs in the form of thalidomide in addition to bortezomib (2 patients) and lenalidomide (1 patient). Immediate specific antiviral therapy was successfully applied with intravenous acyclovir for 10 days, followed by long-term oral famciclovir maintenance. Two patients progressed to have chronic HZ ophthalmicus and postherpetic neuralgia requiring ongoing antiviral therapy and neuroepileptic medications for the neuropathic pain.

Background: A positive Hutchinson's sign indicates an increased risk of ocular involvement in herpes zoster ophthalmicus (HZO). We examined the sensitivity of Hutchinson's sign as an indicator of ocular involvement in a consecutive series of patients presenting with HZO., Methods: We conducted a descriptive observational prospective study of patients > or =18 years old presenting with HZO and consenting to pre-and post-test counselling and HIV and CD4 testing. A full ophthalmological examination focused on the extent of ocular involvement, and the presence of Hutchinson's sign was confirmed by two clinicians., Results: Thirty-three patients were enrolled; 29 were HIV positive, of whom 18 (62%) had not been diagnosed with HIV prior to enrollment. Of the 29 HIV-positive patients, 21 (72%) were Hutchinson's sign positive (HSP), all of whom had intra-ocular involvement (95% confidence interval 88 - 100%). Of the 8 HIV-positive, Hutchinson's sign-negative (HSN) patients, 4 did and 4 did not display intra-ocular involvement. Neither the mean CD4 count nor the average age in the HSP group differed significantly from the HSN group., Conclusion: We confirmed that a Hutchinson's sign- and HIV-positive patient with HZO has a very high positive predictive value for intra-ocular involvement. Neither age nor CD4 count had predictive value for ocular involvement. Young adults presenting with HZO should be suspected of having HIV, and HIV-positive patients with HZO but HSN may still have ocular involvement. All patients with HZO should be seen by an ophthalmologist.

Aim: To describe the course and complications of varicella zoster ophthalmicus (VZO) in patients attending an eye clinic in a community with a high HIV seroprevalence., Study Design: Prospective cohort study of consecutive patients presenting to a tertiary hospital eye clinic with VZO., Method: Patients recruited in 2001 and 2002 received standardized initial topical and systemic management, which was then modified according to complications. Information on the course and complications of the disease was entered in a database prior to statistical analysis., Results: Information on 102 patients who had 250 visits to the eye clinic was collected. HIV serology was positive, negative, and unknown in 66, 22, and 14 patients, respectively. The most common complication was uveitis (40/102). Median delay from onset of rash to starting acyclovir was 5 days. Complications were present in 33 patients at the first visit. Complications were commoner in patients with positive Hutchinson's sign and were less common at CD4 counts <200. At CD4 counts, > or =200 HIV infection had little effect on the course and complications of VZO. Timing of commencement of Acyclovir therapy within or after 72 h had no demonstrable effect on the incidence of new complications., Conclusion: In a resource-limited setting, patients with the following characteristics should have immediate ophthalmic assessment: symptoms suggesting ocular complications or the presence of Hutchinson's sign. All VZO patients should receive antiviral therapy at the first doctor's visit even if they present >72 h after onset of the rash.

Purpose: Varicella zoster virus (VZV)-induced retinitis is characterized by the presence of virus-infected cells in the retinal layer and the ocular infiltration of VZV-specific T cells. Herein, the susceptibility of human retinal pigment epithelial (RPE) cells to VZV infection and the ability of virus-specific CD4(+) T cells to control VZV infection in RPE cells in vitro is addressed., Methods: Human primary RPE cell cultures (n=2) were infected with a VZV strain expressing green fluorescent protein. The infection and viability of infected RPE cells was monitored by flow cytometry or by a fluorescent imager on RPE monolayers. RPE cells, pretreated with or without interferon-gamma (IFN-gamma), were infected with VZV and subsequently cultured with VZV-specific CD4(+) T-cell clones (TCCs; n=3) recognizing disparate VZV proteins presented by different HLA class II alleles. IFN-gamma production and cytotoxicity of the TCCs in response to VZV-infected RPE cells was determined by flow cytometry., Results: Human RPE cells are permissive to a productive VZV infection. VZV-infected RPE cells presented the cognate antigen to the CD4(+) TCCs only if the RPE cells were pretreated with IFN-gamma and expressed the appropriate HLA class II allele. VZV-specific TCCs inhibited productive VZV infection in RPE cells, which was in part attributed to TCC-mediated killing of the VZV-infected RPE cells., Conclusions: The results presented suggest that RPE cells may play a role as retina-resident antigen-presenting cells in the intraocular, VZV-specific, T cell-mediated inflammatory response of VZV-induced uveitis.

Unilateral stromal keratitis is a known rare sequela of primary varicella infection. The authors describe a unique case of immunological (Wessely) ring formation and progressive ring thinning following primary varicella infection in a 6-year-old girl.

Background: Necrotising retinopathy in immunocompromised hosts is characterised by an unfavourable course often with unspecific clinical features. Therefore, differential diagnosis can be critical., History and Signs: A case of an initially therapy-resistant, necrotizing retinopathy is presented in a 65-year-old immunocompromised male patient suffering from chronic B-cell leukemia., Therapy and Outcome: Despite demonstration of cytomegalovirus and Varicella-Zoster-Virus DNA by polymerase chain reaction in vitreous, aqueous humour samples and from retinal biopsy with specific antiviral therapy, a progression of retinal necrosis was noted. Finally Toxoplasma gondii DNA was detected and retinal necrosis resolved after specific treatment. However, visual acuity remains poor because of optic nerve atrophy., Conclusions: The polymerase chain reaction is an important diagnostic tool for differential diagnosis in immunocompromised patients suffering from necrotising retinopathy. If resistance to therapy is noted atypical ocular toxoplasmosis should be considered. The presented case report shows that even multiple infections are possible in the same host.

Since experimental, herpes simplex virus-induced acute retinal necrosis (ARN) develops in mice only if the mice fail to acquire virus-specific delayed hypersensitivity (DH) and despite their production of anti-viral antibodies (i.e. ACAID), I investigated whether a similar situation exists for patients with either varicella zoster virus (VZV)-induced ARN or anterior uveitis caused by VZV. Patients with either acute VZV-induced ARN, anterior uveitis with dermatitis (herpes zoster ophthalmicus, ZO-AU), or anterior uveitis without dermatitis (zoster sine herpete, ZSH-AU) were skin-tested with VZV to evaluate DH. The formal diagnoses of ARN associated with VZV, ZO-AU, and ZSH-AU were established by PCR analysis of the ocular samples and/or by the Goldmann-Witmer coefficient to determine levels of local antibody production. ARN, ZO-AU, and ZSH-AU activity were assessed clinically, and DH skin tests were repeated three months after onset when ocular recovery had taken place. All patients with VZV-induced skin disease alone (control group) displayed intense DH when tested with VZV antigen. In contrast, subsets of patients with ARN or ZO-AU displayed loss of VZV-specific DH. Patients with the most severe ARN or ZO-AU had the lowest DH responses to VZV antigens. Serum anti-VZV antibody titers were higher in ARN patients than in normal controls, and the anti-viral titer correlated inversely with the intensity of anti-VZV DH responses. VZV-specific DH responses were restored in patients who recovered from ARN. Patients with ZSH-AU also failed to display VZV-specific DH. The absence of DH reactivity to VZV antigens (i.e. immune deviation) appears to be a concomitant feature of VZV uveitis of high intensity, implying that virus-specific DH may interfere with the emergence of VZV-induced ARN or anterior uveitis.

Purpose: To evaluate the diagnostic usefulness of enzyme linked immuno-sorbent assay (ELISA) in single serum samples to associate herpes simplex virus (HSV), varicella zoster virus (VZV) or cytomegalovirus (CMV) with viral retinitis as against polymerase chain reaction (PCR) on intraocular specimens. It was also designed to study the seroprevalence in normal healthy individuals, and the genomic prevalence of HSV, VZV and CMV in patients without an active viral inflammatory process., Methods: PCR for the detection of HSV, VZV and CMV genomes was done on 33 and 90 intraocular fluids from viral retinal patients and non-viral controls respectively. ELISA was done on 30 and 100 serum samples from viral retinitis patients and normal healthy controls respectively., Results: PCR did not detect HSV, VZV and CMV genomes except one, in which VZV-DNA was detected. ELISA showed prevalence rates of 28%, 83% and 90% for antibodies against HSV, VZV and CMV respectively in the normal population. In the 30 viral retinitis patients, PCR detected HSV-DNA in 2 (6.7%), VZV-DNA in 7 (23.3%) and CMV-DNA in 6 (20.0%) patients, while ELISA detected antibodies against HSV, VZV and CMV in 13 (43.3%), 24 (80.0%) and 23 (76.7%) patients respectively. ELISA was of value in indirect diagnosis only in 6 (20.0%) as compared to 15 (50.0%) of 30 patients by PCR, this difference was statistically significant (McNemar test, P value = 0.005)., Conclusion: Serology by ELISA is no longer a useful diagnostic tool to associate HSV, VZV and CMV viruses with viral retinitis.

Background: We recently reported that acute retinal necrosis in humans develops in a setting where delayed hypersensitivity (DH) to the varicella-zoster virus (VZV) antigen was absent, implying that virus-specific DH mitigates against acute retinal necrosis., Objective: To determine whether a similar correlation exists for patients with anterior uveitis caused by VZV., Design: Using VZV and purified protein derivative (PPD) antigens to evaluate DH, we skin tested patients with acute, VZV-induced anterior uveitis (herpes zoster ophthalmicus [ZO-AU]) (n = 12), those with uveitis caused by VZV in the absence of dermatitis (zoster sine herpete [ZSH-AU]) (n = 3), and age-matched patients whose ophthalmic herpes zoster was unassociated with uveitis as controls (n = 7). Varicella-zoster virus-induced anterior uveitis was diagnosed by polymerase chain reaction methods and serum antibody titration. Serum samples were collected and analyzed for anti-VZV antibody titers. Anterior uveitis activity was assessed clinically. Delayed hypersensitivity skin tests were repeated in patients with zoster sine herpete 3 months after onset, when ocular recovery had taken place., Results: All patients with VZV-induced skin disease alone (control group) displayed intense DH when tested with VZV and PPD antigens. By contrast, only 4 (33%) of 12 patients with ZO-AU had a positive DH to VZV, whereas 11 (91.6%) of these patients displayed positive PPD skin reactions. The clinical intensity of anterior uveitis correlated negatively with VZV DH responses (P<.05). Serum anti-VZV and anti-herpes simplex virus antibody titers were comparable in DH-positive VZV cases and in DH-negative patients with uveitis. Patients with uveitis and ZSH-AU also displayed absent VZV-specific DH, although their PPD responses were normal., Main Outcome Measures: Varicella-zoster virus-specific DH, PPD-specific DH, VZV-specific antibody titration, and intraocular pressure in patients with ZO-AU., Conclusions: Absence (or loss) of DH reactivity to VZV antigens seems to be a concomitant feature of VZV uveitis of high intensity, implying that virus-specific DH may interfere with the emergence of VZV-induced anterior uveitis, as it does for acute retinal necrosis., Clinical Relevance: In a clinical setting, absence of virus-specific DH to anterior uveitis caused by VZV may not only reveal a possible pathogenic mechanism, but a negative DH response may prove useful in diagnosing ZSH-AU in the acute stage.

Background: Because experimental acute retinal necrosis (ARN) induced by herpes simplex virus in mice develops only if mice fail to acquire virus-specific delayed hypersensitivity (DH), although they produce antiviral antibodies (ie, anterior chamber-associated immune deviation), we sought to determine whether a similar inverse correlation exists for patients with varicella-zoster virus (VZV)-induced ARN., Design: Patients with acute, VZV-induced ARN and age-matched control subjects were skin tested with VZV and purified protein derivative antigens to evaluate DH. Varicella-zoster virus-induced ARN was diagnosed using polymerase chain reaction and intraocular antibody quotient. Serum samples were collected and analyzed for anti-VZV and anti-herpes simplex virus antibody titers. Acute retinal necrosis activity was assessed clinically, and DH skin tests were repeated 3 months after onset when ocular recovery had taken place., Results: Whereas controls displayed intense DH when tested with VZV and purified protein derivative antigens, a subset of patients with ARN displayed absent VZV-specific DH (although their purified protein derivative responses were normal). Patients with the most severe ARN had the lowest DH responses to VZV antigens. Serum anti-VZV antibody titers were higher in patients with ARN than in controls, and antiviral titer correlated inversely with the intensity of anti-VZV DH responses. Varicella-zoster virus-specific DH responses were restored in patients who recovered from ARN., Conclusion: Varicella-zoster virus-ARN develops in a setting where DH reactivity to viral antigens is absent, implying that virus-specific DH might ameliorate the severity of ARN., Clinical Relevance: Linking virus-specific DH to vulnerability to ARN in individuals infected with VZV might reveal an underappreciated pathogenic mechanism.

Purpose: To determine the causative virus in acute retinal necrosis (ARN) syndrome in a series of patients by calculation of modified Witmer coefficients., Design: Noncomparative case series., Participants: Ten patients with ARN syndrome from four medical centers., Methods: Aqueous samples, vitreous samples, or both were collected prospectively during surgery from patients with a clinical diagnosis of ARN syndrome. Serologic measures of intraocular and serum antibodies to potentially causative viruses were measured by enzyme-linked immunosorbent assay., Main Outcome Measures: Modified Witmer coefficients (immunoglobulin G and immunoglobulin A) for herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), varicella zoster virus (VZV), and cytomegalovirus (CMV), as well as adenovirus type 2, were calculated from aqueous or vitreous samples, or both., Results: Intraocular antibody measurements were strongly suggestive of a single diagnosis in 9 of 10 patients tested. Modified Witmer coefficients demonstrated intraocular antibody production to HSV in five patients and antibodies to VZV in four patients, and the measurement was inconclusive in one patient. No patients were positive for adenovirus or CMV. Strain-specific antibody titers demonstrated that all HSV-positive patients were reactive only to HSV-2. Herpes simplex virus type 2 was found predominantly in younger patients with ARN syndrome (mean age, 21.2 +/- 10 years; range, 17-39 years), whereas VZV was more commonly seen in older patients (mean age, 40.8 +/- 12.2 years; range, 29-58 years; P = 0.033). Immunoglobulin A testing confirmed immunoglobulin G testing in all patients examined., Conclusions: Although VZV is thought to be the most common cause of ARN syndrome, HSV-2 is an important cause of ARN syndrome, particularly in younger patients. Because infection with HSV-2 has important medical ramifications, these results suggest that determination of a causal agent should be considered in some cases of ARN syndrome.

Background: The production of intraocular antibodies is considered a specific marker for active infectious uveitis. The aim of our study was to evaluate the diagnostic value of aqueous humor analysis in consecutive patients referred to a tertiary clinical center., Methods: We analyzed 91 paired aqueous humor/serum samples from 89 patients with intraocular inflammation. In 71 patients aqueous humor analysis was used as a positive or negative confirmation of the suspected cause, whereas in 18 patients the clinical diagnosis was completely uncertain. A modified micro-ELISA technique was used to detect intraocular IgG production against Toxoplasma gondii, varicella zoster virus, herpes simplex virus and cytomegalovirus. Statistical analysis was performed using the "Cohen's kappa" test., Results: Specific intra-ocular antibody production could be detected in 12 (66.7%) of 18 patients with uncertain diagnosis. Subsequently initiated therapy led to clinical improvement in 10 patients, whereas 2 patients remained unchanged. In 2 (2.8%) of 71 patients aqueous humor analysis led to revision of the initially suspected etiology and to a change of therapy. Statistical analysis showed a significant accordance of diagnosis and aqueous humor analysis (P<0.01)., Conclusion: In patients with infectious uveitis, analysis of intraocular synthesis of specific antibodies is a valuable tool to establish the etiology rapidly and allows initiation of targeted antimicrobial treatment.

Acute retinal necrosis (ARN) is a rare, potentially blinding retinal disease resulting from ocular infections with herpes simplex virus (HSV) or varicella-zoster virus (VZV). To determine the antigen specificity and functional characteristics of ocular infiltrating T cells in ARN, T cells were isolated and expanded nonspecifically from intraocular fluid (IOF) samples from 2 patients with HSV-1- and 3 with VZV-mediated ARN. HSV-specific T cell reactivity could be detected only in the IOF-derived T cell lines (TCLs) of the 2 patients with HSV-mediated ARN. These TCLs consisted of both HSV type-common and type-specific CD4+ and CD8+ T cell clones (TCCs) with differential T cell receptor usage. Irrespective of their phenotype, the TCCs were cytolytic and secreted interferon-gamma, tumor necrosis factor-alpha, interleukin-4, and interleukin-5. In both patients, the antigen specificity of a substantial number of HSV-1-specific TCCs could be mapped to approximately 0.67-0.73 HSV-1 map units. The data presented suggest the contribution of T cells, specific for the triggering virus, to the pathogenesis of ARN.

Acyclovir treatment of acute herpes zoster speeds rash healing and decreases pain and ocular complications. The limited oral bioavailability of acyclovir necessitates frequent dosing. Valaciclovir, the l-valyl ester of acyclovir, is rapidly and almost completely converted to acyclovir in vivo and gives three- to fivefold increases in acyclovir bioavailability. In a randomized, double-blind, multicenter study, the safety and efficacy of oral valaciclovir given at a dosage of 1,000 mg three times daily for 7 or 14 days and oral acyclovir given at a dosage of 800 mg five times daily for 7 days were compared in immunocompetent adults aged > or = 50 years with herpes zoster. Patients were evaluated for 6 months. The intent-to-treat analysis (1,141 patients) showed that valaciclovir for 7 or 14 days significantly accelerated the resolution of herpes zoster-associated pain (P = 0.001 and P = 0.03, respectively) compared with acyclovir; median pain durations were 38 and 44 days, respectively, versus 51 days for acyclovir. Treatment with valaciclovir also significantly reduced the duration of postherpetic neuralgia and decreased the proportion of patients with pain persisting for 6 months (19.3 versus 25.7%). However, there were no differences between treatments in pain intensity or quality-of-life measures. Cutaneous manifestations resolved at similar rates in all groups. Adverse events were similar in nature and prevalence among groups, and no clinically important changes occurred in hematology or clinical chemistry parameters. Thus, in the management of immunocompetent patients > or = 50 years of age with localized herpes zoster, valaciclovir given at 1,000 mg three times daily for 7 days accelerates the resolution of pain and offers simpler dosing, while it maintains the favorable safety profile of acyclovir.

Background: Intraocular antibodies have been measured as a diagnostic aid in necrotizing retinitis but interpretation of results may be difficult., Methods: Vitreous or aqueous and serum immunoglobulin G antibodies to toxoplasmosis, cytomegalovirus, herpes simplex virus I and II, and varicella zoster virus were subjected to enzyme-linked immunosorbent assay in 27 patients with necrotizing retinitis and 15 control patients. A quotient was derived quantitating the amount of excess antibody in the eye compared to serum. Different interpretative rules were analyzed to determine which yielded the highest sensitivity and specificity., Results: The highest intraocular antibody relative to serum among the 4 antibodies correctly predicted the final clinical diagnosis in 21 of 27 patients, for a sensitivity of 78% and a specificity of 90%. Interpretive rules that relied on a high numeric value of the antibody quotient or did not consider the relative ranking of the four antibody quotients were less sensitive and specific because multiple antibodies were detected in most eyes. The technique was safe and rapid., Conclusion: Interpretation of antibody titers in intraocular fluids is facilitated by testing several relevant antibodies and comparing the results. The technique may be helpful to diagnose necrotizing retinitis and to ascertain viral cause in acute retinal necrosis.

Purpose: To explore the possibility that inoculation of the eyes of African green monkeys with simian varicella virus (SVV) induces the symptoms of herpes zoster ophthalmicus (HZO), as seen in humans, and to develop a realistic and reproducible animal model of herpes zoster ophthalmicus for experimental studies., Methods: In the first experiment, the right eyes of three African green monkeys were inoculated by intrastromal and subconjunctival injections with a suspension of SVV-infected Vero cells. In the second experiment, three additional monkeys were pretreated with intramuscular injections of methylprednisolone (41 mg/kg) for 7 days before ocular inoculation with SVV and for 3 weeks at 14 mg/kg after virus inoculation. The eyes were examined by slit-lamp biomicroscopy. Histologic, immunohistochemical, and electron microscopic studies were performed., Results: In the first experiment, all three animals developed high titers of anti-SVV antibodies (IgG). Diffuse stromal opacity, with keratitic precipitates, stromal edema, and mild vascularization of the cornea, appeared 12 to 14 days after inoculation. The onset of ocular disease was correlated with the rise in serum antibody levels. There was no clinical evidence of a systemic viral infection resulting from the corneal inoculations in these monkeys. In the second experiment, all three animals treated with methylprednisolone developed severe ocular pathology within 1 week of inoculation. The clinical appearance of the diseased eyes strongly indicated that local viral infection had occurred. Dendritiform keratitis, corneal erosion, and stromal necrosis with vascularization of the cornea was seen in all the eyes. The disease resolved within 4 to 5 weeks of inoculation, leaving opaque, vascularized corneas. Histologic studies showed that inflammatory cells and viral antigens were widespread throughout the diseased corneas. A high titer of anti-SVV antibody (IgG) was detected in the immunosuppressed monkeys, but no evidence of systemic viral infection was observed., Conclusions: The authors propose that inoculation of the eyes of methylprednisolone-treated African green monkeys with simian varicella virus provides an appropriate animal model for studies of the virology and immunopathology of ocular varicella virus infection.

Purpose: The purpose of this study was to analyse our ARN-patients, perform an extensive review of the literature, suggest a physiopathogenic hypothesis for the disease that should influence the therapeutical approach of these cases., Patients and Methods: From 1985 to 1993, 15 HIV-negative cases of ARN were seen in our clinic. Eleven cases were analysed prospectively: the herpetic agent involved in each case was searched for by the determination of intraocular specific antibody production and a complete immunological work-up was performed., Results: Our collective included 4 cases of bilateral ARN (BARN). In 9 cases the clinical presentation was that of a typical ARN, in 3 cases ARN was of the "mild-type" and in 3 cases lesions were multifocal involving initially the posterior pole resembling the clinical picture of PORN (progressive outer retinal necrosis). The viral agent was varicella-zoster virus in 7 cases, herpes simplex virus in 3 cases, cytomegalovirus in 1 case and was not determined in 4 cases. In the 216 published cases a state of immunodepression was found in 15.7%. In our group with systematic immunological work-up this rate was 46%., Conclusion: This is in support of the thesis that an immune dysfunction is probably at the origin of ARN. We therefore suggest to avoid to add systemic steroids to the specific antiviral therapy but to treat inflammation by periocular steroids.

Humoral immune parameters were measured in 93 patients suffering from ophthalmic herpes zoster. The control group consisted of 31 other ophthalmic patients. In all cases, electrophoresis, immunoglobulins, acutephase proteins, immune complexes, antinuclear antibody and complement components were determined as well. In patients suffering from ophthalmic herpes zoster the main immunological deviations among the humoral parameters were found in the non-specific immune response. These alterations were comparable with the extent and severity of the pathological processes. Para-proteins were detected in 12% of the patients. In contrast they were not present in the control group.

Background: Since the era of bone marrow transplantation, the picture of acute and/or chronic transplant reaction of the host cells against grafted bone marrow has become more frequent. The so-called adaptive immune therapy bases on the fact that patients who present with a low grade of GvHD less often suffer from a relapse of the malignant leukaemic disease. Therefore, new therapeutic regimen are now performed which keep the patient on a low level of GvHD to prevent a recurrence of leukaemia. Here a close cooperation of oncologists and ophthalmologists becomes more and more important to estimate the stage of GvHD., Patients: Demonstrating two case reports, we report on the ophthalmological symptoms of acute and chronic GvHD. Both patients presented with acute ocular GvHD as well as with signs of chronic ocular GvHD. Concerning the ophthalmological symptoms, in acute or chronic GvHD the conjunctival involvement is most important. There is a lymphocytic infiltration of the conjunctiva and of the lacrimal glands which leads to an extreme sicca-syndrome. The acute GvHD of the conjunctiva can be classified into 4 stages: injection/exudation and chemosis/formation of pseudomembranes/defects of the corneal epithelium. These stages correlate directly to the prognosis of the survival time of the patient. A pathognomonic sign for the chronic GvHD of the conjunctiva are the fibrous-scarry Arlt-lines of the tarsal conjunctiva., Conclusions: All patients who underwent a bone marrow transplantation for leukaemia need to be followed up closely to estimate the level of GvHD they are in. This applies especially to those patients who are treated according to the regimen of adaptive immune therapy. A close cooperation of oncologists and ophthalmologists during adaptive immune therapy is mandatory, as the ophthalmologist can provide important information to help to grade the level of GvHD, judging by the morphological picture at the slit lamp.

The acute retinal necrosis (ARN) syndrome is an increasingly occurring entity characterized by the triad of acute confluent peripheral retinitis with papillitis and anterior-chamber uveitis. We present case reports on four patients (age, 12-65 years) with an ARN syndrome caused by herpes simplex or varicella zoster virus and discuss diagnostic and therapeutic modalities. Immediate antiviral therapy in three patients exhibiting the typical clinical features reduced the intraocular inflammation. However, due to proliferative vitreoretinopathy with peripheral retinal necrosis, vitrectomy with encircling band and silicone oil instillation was necessary in all patients. The suspected diagnosis of an ARN syndrome induced by herpes simplex virus (HSV) was confirmed in one case during the early stage of the disease by the detection of increased levels of HSV-IgA in the vitreous and in another case by the measurement of increased titers of HSV-IgG in the vitreous. For the first time, we found intraocular HSV DNA sequences using the polymerase chain reaction (PCR) in one of these patients. In a fourth patient intraocular varicella zoster virus (VZV) infection was confirmed by the detection of elevated VZV-IgA levels and by positive PCR in the intraocular fluids. Two patients who were diagnosed and treated early retained a visual acuity of 0.4 and 0.5, respectively, whereas in the other two patients, whose diagnosis and therapy were delayed (> 6 weeks), visual acuity was reduced to light perception. We conclude that use of the PCR in the intraocular fluids together with detection of autochthonous antibodies in the vitreous seem to be the most important diagnostic laboratory tools.(ABSTRACT TRUNCATED AT 250 WORDS)

Corneal endotheliitis in the narrower sense is the term applied to immune reactions directed against the endothelial cells themselves. Virus antigens, histocompatibility antigens and autoantigens in the cell membrane represent the target for immune attack. The most significant clinical sign of endotheliitis is a strict correlation between the area of endothelial damage and the area of the (immune) precipitates.

We assessed delayed dermal hypersensitivity to varicella-zoster virus by a varicella skin test in 12 patients (nine women and three men ranging in age from 27 to 85 years) with ophthalmic herpes zoster during the acute stage and in a group of 27 healthy controls (15 women and 12 men ranging in age from 18 to 58 years). Of the 27 healthy individuals, 25 had positive skin test reactions whereas only one of the 12 patients with ophthalmic herpes zoster had a positive skin test reaction within two weeks after the onset of the eruption, suggesting that cellular immunity to varicella-zoster virus antigens is impaired in the development of ophthalmic herpes zoster. Our study also showed that the varicella skin test is a convenient way to diagnose ophthalmic herpes zoster during the acute stage of the disease.

Herpes zoster of the ophthalmic division of the left fifth cranial nerve with contralateral hemiparesis was observed in a 30-year-old man. Left carotid angiography showed segmental constrictions consistent with cerebral arteritis, possibly provoked by direct viral infection along the intracranial part of the ophthalmic nerve. An ischaemic lesion revealed by computed tomographic scan was considered secondary to arteritis and responsible for the hemiparesis. The presence of an immune response within the blood-CSF barrier was suggested by an increase of oligoclonal CSF IgG and IgA.

Herpes stromal disease is due to direct damage as a result of viral replication, virally induced immune mechanisms, or a combination of the two. Viral replication may have a major initiating role in the production of herpes simplex and herpes zoster induced stromal disease, and steroids may initially be harmful in their treatment. On topical antiviral drugs alone, in patients who never previously had had topical steroids, 14 of 15 cases of herpes simplex induced disciform keratitis responded favourably in an average of 44 days of treatment. This compared with one out of 14 responding if steroids had previously been used, 13 of 14 requiring topical steroids and an average 112 days' treatment. In herpes zoster stromal disease cases 78% had epithelial involvement, 54 of 57 responded to topical antivirals alone without the use of steroids, 2% recurred, and treatment averaged a total of 62 days. If steroids were used alone or in combination with antivirals, there was a 50% recurrence rate and 200 day total treatment duration.

A 55-year-old man with herpes zoster oticus and minimal cutaneous involvement developed reversible optic neuropathy, and ocular motor and cerebellar abnormalities. Serologic changes confirmed infection with herpes zoster. A demyelinating process seems likely to have been responsible for these lesions. It is suggested that herpes zoster antibody titers should be measured whenever the syndrome of polyneuritis cranialis of acute onset is being investigated.

This report proves the relationship between herpes zoster ophthalmicus and seropositivity for HTLV-III in young and often apparently healthy African patients. The ophthalmologist should screen patients with herpes zoster ophthalmicus for antibodies against HTLV-III in areas where this virus is endemic or if the patient belongs to a known risk group. If the test is positive, the patient should be instructed about the infectious nature of his condition to prevent spread of this sexually transmitted disease. As the rate of corneal involvement and postherpetic neuralgia are very high in these patients, it would be worthwhile to ascertain whether routine use of acyclovir treatment in HTLV-III seropositive patients with herpes zoster has a beneficial effect on these complications.