Digital droplet polymerase chain reaction analysis of common viruses in the aqueous humour of patients with Posner-Schlossman syndrome in Chinese population.

BACKGROUND: To compare the detection results consistency of quantitative polymerase chain reaction (qPCR) and digital droplet polymerase chain reaction (ddPCR), and determine the value of ddPCR for viral detection in the aqueous humour. METHODS: A total of 130 aqueous humour samples were collected, including 60 patients with Posner-Schlossman syndrome (PSS) in case group and 70 elderly patients with senile cataract in control group. The target nucleic acid fragments of human cytomegalovirus (HCMV), herpes simplex virus, Epstein-Barr virus and varicella zoster virus in aqueous humour were analysed by qPCR and ddPCR, respectively, for the diagnosis and curative effect monitoring of pathogen-induced PSS. Samples with inconsistent results were verified by next-generation sequencing. RESULTS: There were 27 and 20 HCMV-positive cases detected in the case group by ddPCR and qPCR, respectively. ddPCR increased the sensitivity for the HCMV virus detection from 400 to 100 copies/mL. No other pathogens were found in this study. The results of ddPCR were consistent with that of next generation sequencing. The mean (SD) of Lg (HCMV copies/mL) detected by ddPCR and qPCR were 1.66 (1.92) and 1.10 (1.61), respectively (P < 0.001). Compared with qPCR, results of ddPCR showed better consistency with validity of clinical treatment. All patients with ddPCR-positive results had good validity on antiviral therapy, exhibiting anterior chamber inflammation remission, resolution of corneal oedema and good IOP control within 1 month. CONCLUSIONS: HCMV was the leading cause of pathogen-induced PSS in the Chinese population. ddPCR was a promising tool for early detection, accurate diagnosis and therapeutic validity monitoring of pathogen-induced PSS. The high sensitivity of ddPCR could avoid repeated anterior chamber tap.

Polymorphisms in cytomegalovirus genotype in immunocompetent patients with corneal endotheliitis or iridocyclitis.

Cytomegalovirus (CMV) that caused corneal endotheliitis and iridocyclitis in immunocompetent patients was genotyped. The gB type1 was detected in seven endotheliitis samples (77.8%) and five iridocyclitis samples (100%), and the gB type 3 was detected in two endotheliitis samples (22.2%). The UL144 type 1 was found in five endotheliitis samples (45.5%) and five iridocyclitis samples (83.3%). The UL144 type 2 was found in two endotheliitis samples (18.2%) and one iridocyclitis sample (16.7%). The gB type 1 was predominant in endotheliitis and iridocyclitis, and the CMV genotypes in eyes with endotheliitis and iridocyclitis were similar.

[Endotoxin Is a Companent in Pathogenesis of Chronic Viral Diseases].

The level of endotoxin and indicators of activity of antiendotoxin immunity (antibody concentration to glycolipid Re-chemotype and general antigen of enterobacteria) were estimated in serum of 174 patients with persistent viral infections (viruses: herpes simplex, hepatitis C, human immunodeficiency). The presence of markers of systemic inflammatory response syndrome (interleukin IL-1ß) and acquired immunodeficiency (CD4+) in HIV-infected patients were also determined. Persistent viral infections are accompanied by endotoxin aggression intestinal origin (caused by them), which is able to induce the development of systemic inflammatory response syndrome. In HIV-infected patients with this syndrome is cyclical, when the phase of hyperactivity replaced immunodeficiency. Schematically, this process can be represented as the following sequence of events: HIV-mediated damage to the intestinal barrier--the development of endotoxin aggression--induction ofsystemic inflammatory response syndrome--the depletion of the immune system, which is transient and is related to the duration of activity of the virus replication cycle, i.e., with damage to enterocytes. Using antiendotoxin component (means of reducing levels of endotoxin in the blood) in the scheme of treatment of persistent viral infections can serve as an element of a successful prevention of complications.

Overview of Cytomegalovirus Ocular Diseases: Retinitis, Corneal Endotheliitis, and Iridocyclitis.

Cytomegalovirus (CMV) infection is a significant clinical concern in newborns, immunocompromised patients with acquired immunodeficiency syndrome (AIDS), and patients undergoing immunosuppressive therapy or chemotherapy. CMV infection affects many organs, such as the lungs, digestive organs, the central nerve system, and eyes. In addition, CMV infection sometimes occurs in immunocompetent individuals. CMV ocular diseases includes retinitis, corneal endotheliitis, and iridocyclitis. CMV retinitis often develops in infected newborns and immunocompromised patients. CMV corneal endotheliitis and iridocyclitis sometimes develop in immunocompetent individuals. Systemic infections and CMV ocular diseases often require systemic treatment in addition to topical treatment.

High concordance of intraocular antibody synthesis against the rubella virus and Fuchs heterochromic uveitis syndrome in Slovenia.

PURPOSE: To prospectively study the relationship between Fuchs heterochromic uveitis syndrome (FHUS) and intraocular production of specific antibodies against the rubella virus (RV) in Slovenia. METHODS: Using the Goldmann-Witmer coefficient technique, intraocular synthesis of specific antibodies against RV, herpes simplex virus, varicella-zoster virus, cytomegalovirus (CMV) and Toxoplasma gondii-specific immunoglobulin G antibodies was performed in 12 consecutive patients with clinically diagnosed FHUS and 12 patients with idiopathic recurrent unilateral anterior uveitis (AU) without clinical features of FHUS. RESULTS: Specific intraocular antibody synthesis against RV with a positive Goldmann-Witmer coefficient was proven in 11 of 12 (92%) FHUS patients, and in none of the non-FHUS AU patients (Fisher's exact test <0.0001). In one patient with FHUS, specific antibodies against RV and varicella-zoster virus were concurrently detected. Specific antibodies against cytomegalovirus were detected in one patient with unilateral recurrent AU. CONCLUSIONS: Intraocular production of specific immunoglobulin G against RV was proven in the majority of tested cohort of FHUS patients from Slovenia as compared to the group of patients with idiopathic AU, which suggests that RV is involved in the pathogenesis of FHUS in this geographic area.

Polymorphisms of the cytomegalovirus glycoprotein B genotype in patients with Posner-Schlossman syndrome.

AIMS: The aim of this observational study was to report the distribution of glycoprotein B (gB) genotypes in the eyes of cytomegalovirus (CMV) positive patients with Posner-Schlossman syndrome (PSS), and to investigate their clinical characteristics and outcomes. METHODS: We collected aqueous humour samples from 165 patients clinically diagnosed with PSS between 2017 and 2019. PCR was performed to analyse the CMV DNA and identify the gB genotypes in the samples. Clinical characteristics and responses to antiviral treatment were compared among patients with different gB genotypes. RESULTS: CMV DNA was detected in 94 (56.97%) of the 165 aqueous humour specimens analysed. Owing to the quantity requirement for CMV gB genotype analysis, results could be obtained from only 14 specimens. CMV gB type 1 was detected in 11 samples (78.6%), whereas CMV gB type 3 was detected in three samples (21.4%). No other gB genotypes or mixed genotypes were detected. Overall, 9.1% (1/11) of the patients in the gB type 1 group and 66.7% (2/3) of the patients in the gB type 3 group had bilateral attacks (p=0.093). The concentration of anti-CMV immunoglobulin G (IgG) in the type 1 group was 0.94±0.79 s/co (ratio of aqueous humour CMV IgG/serum CMV IgG to aqueous humour albumin concentration/serum albumin concentration), whereas that in the type 3 group was 0.67±0.71 s/co. CONCLUSION: Genotype 1 was the most prevalent genotype in the aqueous humour of CMV-infected patients with PSS. Bilateral attack was predominant among patients with gB genotype 3. CMV gB gene may be related to the pathogenicity of CMV virus strain in patients with PSS.

Cytokine Changes in the Aqueous Humor in Rubella-Related Fuchs Heterochromic Iridocyclitis.

This retrospective study is aimed at determining the correlation between cytokine levels and virus status in the aqueous humor of 38 patients with Fuchs heterochromic iridocyclitis (FHI) with/without a viral presence between May 2017 and January 2020. The levels of cytokines were analyzed in the groups with and without virus-related FHI. Among the patients, 50% had rubella virus, 5.26% had cytomegalovirus, and 2.63% had herpes simplex virus infections. The expression of interleukin-6 (IL-6) and IL-8 was significantly higher, and that of basic fibroblast growth factor (bFGF) was significantly lower in the virus-positive group than in the virus-negative group (P = 0.015, P = 0.001, and P = 0.001, respectively). Although there was no significant difference in the mean expression of vascular cell adhesion protein 1 (VCAM-1), IL-10, and vascular endothelial growth factor (VEGF), that of VCAM-1 and IL-10 was higher (M = 1338 and M = 1390, respectively; M = 6.225 and 10.600, respectively) and that of VEGF was lower (M = 134.5 and M = 38.70, respectively) in the virus-positive group than in the virus-negative group. Similar findings were observed for the expressions of IL-6, IL-8, and bFGF in the rubella-positive and rubella-negative groups. Viral presence was highly related to FHI, especially that of the rubella virus. High levels of inflammatory cytokines and low levels of neovascularization-related factors are involved in rubella-related FHI. These study findings could be helpful in the diagnosis and treatment of FHI.

Rubella virus as a possible etiological agent of Fuchs heterochromic iridocyclitis.

BACKGROUND: To determine whether rubella virus is involved in the pathogenesis of Fuchs heterochromic iridocyclitis (FHI). METHODS: Fourteen patients (14 eyes) diagnosed with FHI based on characteristic ocular manifestations and eight control subjects were studied. Aqueous humor (AH) samples from 14 FHI patients and one vitreous sample from a FHI patient were analyzed for intraocular antibody production against rubella virus by calculation of the Goldmann-Witmer coefficient (GWC). Viral detection by nested polymerase chain reaction and isolation by culture in RK-13 cells were conducted in nine FHI patients. In addition to laboratory examinations, medical history of rubella virus vaccination was also obtained. RESULTS: Ten patients with FHI examined showed intraocular synthesis of rubella virus antibodies (GWC > 3). A high index of rubella virus antibody production was also found in the vitreous sample (GWC = 30.6). GWC in all control subjects were below detectable level. The rubella genome was detected in two of nine patients, and rubella virus was isolated from one of nine patients with FHI. None of the patients with FHI had been vaccinated against rubella. CONCLUSIONS: Our laboratory data strongly suggest a relationship between FHI and rubella virus.

Intraocular antibody synthesis against rubella virus and other microorganisms in Fuchs' heterochromic cyclitis.

INTRODUCTION: Fuchs' heterochromic cyclitis (FHC) is a common intraocular disease of uncertain etiology that has recently been related to rubella virus (RV) infection. METHODS: We investigated the synthesis of RV-specific IgG using aqueous humor and serum samples from 63 consecutive patients with FHC. In addition, intraocular immunoglobulin G production against herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV) and toxoplasma gondii was determined. In 20 patients, the detection of RV RNA was additionally performed by RT-PCR on the E1 gene. Forty-six patients with HSV- and VZV-associated uveitis, HLA B-27 positive anterior uveitis, and Posner-Schlossman syndrome served as controls. RESULTS: Specific intraocular antibody synthesis against RV was confirmed in all 63 FHC patients, whereas none of the 46 controls was positive for RV IgG. Interestingly, in 11 patients with positive RV IgG synthesis, additional HSV (eight), VZV (one) and CMV (two) specific antibodies could be detected. Only twice was viral RNA detectable by PCR in a patient with FHC. CONCLUSIONS: In this largest reported series of FHC patients, we detected a strong association between FHC and intraocular antibody synthesis against rubella virus. Furthermore, in 11 patients, it was possible to confirm an additional intraocular antibody synthesis, in particular HSV. PCR-positive results in the aqueous humor were exclusively obtained for RV. In contrast to other studies, the RV genome could only be identified in two patients (10%).

Effects of ROCK Inhibitors on Apoptosis of Corneal Endothelial Cells in CMV-Positive Posner-Schlossman Syndrome Patients.

Purpose: To examine the role of aqueous tumor necrosis factor α (TNF-α)-RhoA-Rho kinase (ROCK) signaling in cytomegalovirus (CMV)-induced apoptosis and the barrier function of cultured human corneal endothelial cells (hCECs) in CMV-positive Posner-Schlossman syndrome (CMV+/PSS) patients. Methods: Aqueous levels of TNF-α, IL-8, IL-10, and several other cytokines in 19 CMV+/PSS patients and 20 healthy control subjects were quantitated using a multiplex assay. The expression of active RhoA in hCECs post-CMV infection was determined using western blotting (WB). The expression levels of TNF-α and nuclear factor kappa B (NF-κB) in CMV-infected hCECs were examined by immunocytochemistry (ICC) and WB with and without ROCK inhibitors. The apoptotic rate and barrier integrity in CMV-infected hCECs were also examined. Results: The expression levels of TNF-α, monocyte chemoattractant protein-1 (MCP-1), IL-8, and IL-10 were upregulated in the aqueous humor of CMV+/PSS patients, and among these upregulated cytokines aqueous TNF-α was negatively correlated with the number of corneal endothelial cells. In CMV-infected hCECs, upregulation of TNF-α and NF-κB was determined by WB and ICC. In hCECs, CMV infection induced apoptosis and significantly impaired cell-cell contacts, effects that were attenuated by treatment with a ROCK inhibitor. Conclusions: Aqueous TNF-α was upregulated in CMV+/PSS patients, which may have triggered corneal endothelial cell loss. Modulation of TNF-α, including its downstream Rho-ROCK signaling, could serve as a novel treatment modality for corneal endothelial cell loss in CMV+/PSS patients.

Ocular manifestations associated with chikungunya.

PURPOSE: To report ocular manifestations associated with chikungunya. DESIGN: Retrospective, nonrandomized, observational case series. PARTICIPANTS: Nine chikungunya patients with ocular involvement. METHODS: All patients with chikungunya infection presenting with ocular complaints from September 2006 to October 2006 were included in the study. The infection was confirmed by demonstration of chikungunya immunoglobulin M antibody in sera of all patients. All patients underwent an ophthalmic examination including fundus photography, fundus fluorescein angiography, confocal microscopy of keratic precipitates, and optical coherence tomography. Positive ocular changes were recorded and tabulated. MAIN OUTCOME MEASURES: Characteristics, frequency, and locations of ocular lesions found in the participants. RESULTS: There were 9 patients with ocular lesions; 1 had nodular episcleritis, 5 presented with acute iridocyclitis, and 3 had retinitis. Four to 12 weeks before the development of ocular manifestations, all of these patients had fever. Although there were no specific changes of iridocyclitis that were diagnostic of the fever, the retinal changes were consistent with viral retinitis. All patients recovered from the infection with relatively good vision. CONCLUSION: It appears that iridocyclitis and retinitis are the most common ocular manifestations associated with chikungunya, with a typically benign clinical course. Less frequent ocular lesions include episcleritis. All the patients responded well to the treatment with preservation of good vision. To the best of our knowledge, similar ocular manifestations associated with chikungunya infection have not been reported. In the differential diagnosis of iridocyclitis and retinitis with features suggestive of a viral infection, the entity of chikungunya-associated ocular changes should be considered in the regions affected by the epidemic.

Rubella virus-associated uveitis: clinical manifestations and visual prognosis.

PURPOSE: To investigate the clinical profile of patients with chronic anterior uveitis and intraocular analyses positive for intraocular Rubella virus infection and assess eventual similarities to Fuchs heterochromic uveitis (FHU). DESIGN: Retrospective case-control study. METHODS: Clinical records of 30 patients with anterior uveitis positive for intraocular antibody production against Rubella virus by Goldmann-Witmer coefficient determination and/or polymerase chain reaction were reviewed and compared with clinical records of 13 patients with chronic anterior uveitis of undetermined origin. Multiple variables were assessed and patient records were evaluated at onset and at one year after their first visit to the University Medical Center Utrecht. RESULTS: Patients with Rubella virus-associated uveitis were younger at time of initial ophthalmologic presentation (P = .014). Rubella virus-positive patients presented more frequently with unilateral ocular disease (P < .001), keratic precipitates (KPs; P = .014), iris atrophy and/or heterochromia (P = .051), associated vitreous opacities (P = .024), and cataract (P = .004). Also, the combination of KPs, absence of posterior synechiae, cataract, and vitreous opacities occurred more often in the Rubella virus-positive group (P = .026) and the presence of three or four of these criteria occurred more frequently in the Rubella virus-positive group (P = .004). CONCLUSIONS: Rubella virus causes a distinct clinical spectrum of ocular symptoms similar to the FHU syndrome, which suggests that Rubella virus might be involved in the pathogenesis of FHU.

Clinical features of cytomegalovirus anterior uveitis in immunocompetent patients.

PURPOSE: To describe the clinical presentation of cytomegalovirus (CMV) anterior uveitis in human immunodeficiency virus (HIV)-negative patients. DESIGN: Retrospective, interventional case series. METHODS: HIV-negative patients with anterior uveitis associated with elevated intraocular pressure (hypertensive anterior uveitis) seen at the Singapore National Eye Centre had their aqueous analyzed for viral deoxyribonucleic acid by polymerase chain reaction, and their records were reviewed for demographic data, ocular findings, laboratory results, and treatment. RESULTS: Aqueous was obtained from 105 of 106 eligible eyes. Twenty-four eyes demonstrated positive results for CMV (22.8%). Eighteen eyes had Posner-Schlossman syndrome (PSS; 75%) at presentation, five eyesba had Fuchs heterochromic iridocyclitis (FHI; 20.8%), and one eye had a presumed herpetic anterior uveitis. Twelve of the 24 eyes were treated with ganciclovir. Of the 12 who completed treatment, all responded clinically, and their aqueous demonstrated negative results for CMV on repeat testing. However, nine had recurrences within eight months of stopping treatment and required further courses of ganciclovir. The 81 CMV-negative eyes included 30 with PSS, 11 with FHI, 27 with uveitic glaucomas of unknown cause, and 13 with presumed herpetic anterior uveitis. CONCLUSIONS: CMV anterior uveitis is not uncommon in our immunocompetent patients and it may present as a recurrent acute or chronic inflammation, resembling PSS, herpetic anterior uveitis, or FHI.

Rubella virus-associated uveitis in a nonvaccinated child.

PURPOSE: To report presumed Fuchs heterochromic uveitis (FHU) associated with Rubella virus (RV)-specific intraocular antibody production in a child who was not vaccinated against rubella. DESIGN: Observational case report. METHODS: We examined a 13-year-old boy with chronic anterior uveitis complicated by mature cataract. Two aqueous humor (AH) samples taken with an interval of four weeks were analyzed for intraocular antibody production against RV by calculation of the Goldmann-Witmer coefficient. RESULTS: The patient showed all the clinical signs for FHU: iris atrophy, stellate keratic precipitates, and cataract. Analysis of the AH demonstrated intraocular antibody production against RV in two sequential samples. CONCLUSIONS: The data show that RV-associated uveitis can already present during childhood. Moreover, this finding suggests that nonvaccinated children may be at risk to develop uveitis after RV infection.

Epidemiologic relationship between fuchs heterochromic iridocyclitis and the United States rubella vaccination program.

PURPOSE: To investigate an epidemiologic association between Fuchs heterochromic iridocyclitis (FHI) and the rubella vaccination program in the United States. DESIGN: Observational case series. METHODS: The percentages of patients with FHI, idiopathic chronic iridocyclitis, and idiopathic chronic granulomatous iridocyclitis at the University of Illinois were compared over time. Analysis of country of origin (United States vs foreign-born) was also performed. Findings were correlated with implementation of the rubella vaccination program in the United States in 1969. RESULTS: A total of 3,856 patients were seen between 1985 and 2005. Percentages of patients with FHI and idiopathic chronic granulomatous iridocyclitis born between 1919 and 1958 were similar (FHI 3.51% to 5.19%; idiopathic chronic granulomatous iridocyclitis 3.51% to 4.72%), with more variability in the idiopathic chronic iridocyclitis group (6.63% to 11.32%). A 64.8% reduction in FHI subjects was seen for those born the following decade (1959 to 1968). An additional 39.7% drop in FHI occurred in patients born between 1969 and 1978. Only one patient with FHI was born during the decade 1979 to 1988. The trend over time for FHI differed significantly from idiopathic chronic iridocyclitis (P = .0007) and idiopathic chronic granulomatous iridocyclitis (P = .0002), with no difference between the controls (P = .5437). The percentage of foreign-born patients with FHI increased after the institution of the rubella vaccination program (42% to 55%) compared with those born in previous decades (24% to 25%). This was not observed in the controls. CONCLUSION: FHI is less common in patients born since the introduction of the US rubella vaccination program, with a corresponding increase in percentage of foreign-born cases. This epidemiologic study supports a relationship between the rubella virus and FHI.

Rubella virus is associated with fuchs heterochromic iridocyclitis.

PURPOSE: To determine whether rubella virus (RV) is involved in the pathogenesis of Fuchs heterochromic iridocyclitis (FHI). DESIGN: Retrospective patient-controlled study. METHODS: Intraocular immunoglobulin G production against RV, herpes simplex virus (HSV), varicella zoster virus (VZV), and Toxoplasma gondii was determined in the aqueous humor of 14 patients with FHI, 13 control subjects with herpetic uveitis anterior, and 19 control subjects with ocular toxoplasmosis by calculation of the Goldmann-Witmer coefficient (GWC). RESULTS: All patients and control subjects were seropositive for RV. Intraocular antibody production (GWC >3) against RV was found in 13 of 14 patients (93%) with FHI. Intraocular antibody production against HSV, VZV, or T gondii was not detected. None of the control subjects with herpetic uveitis anterior or with toxoplasma chorioretinitis had a positive GWC for rubella virus (P < .0001, Fisher exact test). CONCLUSION: Rubella virus, but not HSV, VZV, or T gondii, is associated with FHI.

Diagnosis and treatment of cytomegalovirus iridocyclitis without retinal necrosis.

AIM: To describe the diagnostic and therapeutic management of cytomegalovirus (CMV) anterior uveitis unassociated with retinal necrosis in immunocompetent patients. METHODS: Patients referred between 2001 and 2003 for management of unilateral, chronic, recurrent uveitis associated with secondary glaucoma underwent extensive investigation including laboratory tests for herpes virus infections. Specific antiviral treatment was initiated in all cases and the level of ocular inflammation was evaluated during the follow up. RESULTS: Five patients, three men and two women, were included. Median age was 50 years old (range 30-80 years). Anterior unilateral uveitis without iris atrophy was observed in all cases. Uveitis was chronic in three cases and recurrent in two cases. Glaucoma was observed in all patients with a median intraocular pressure of 30 mm Hg (range 22-43 mm Hg). Five patients responded initially to specific anti-CMV therapy. Even though glaucoma surgery was necessary in two cases, both ocular inflammation and glaucoma were controlled in all cases. Relapses occurred in three cases after cessation of therapy, requiring prolonged maintenance therapy with valganciclovir. CONCLUSIONS: CMV infection and specific antiviral therapy should be considered in all cases of relapsing or chronic iridocyclitis and secondary glaucoma. Maintenance regimens of valganciclovir may be necessary to prevent further relapses.

Rubella Virus-associated Anterior Uveitis in a Vaccinated Patient: A Case Report.

Rubella virus is involved in the pathogenesis of Fuchs heterochromic uveitis and almost all cases in Europe show an active antibody production in the aqueous humor against rubella virus. Herein we report a case of a fully vaccinated patient with common variable immunodeficiency who developed unilateral Fuchs heterochromic uveitis secondary to rubella virus which was proven by intraocular fluid examination. Awareness of rubella associated anterior uveitis should remain also in vaccinated patients, especially those without a fully competent immune system.

Trabeculectomy ab interno (trabectome): yet another possibility in the treatment of uncontrolled glaucomatocyclitic crisis under systemic valganciclovir therapy?

PURPOSE: To assess the outcome of trabectome surgery in the treatment of glaucomatocyclitic crisis (Posner-Schlossman syndrome) in patients with uncontrolled intraocular pressure (IOP). PATIENTS/METHODS: Trabectome surgery was performed in seven patients with diagnosed glaucomatocyclitic crisis and uncontrolled IOP where cytomegalovirus DNA was verified by polymerase chain reaction in aqueous humour samples. All patients were treated with oral valganciclovir. After surgery the patients were followed-up for 12 months. RESULTS: Mean IOP before trabectome surgery was 40±10 mm Hg (range 33-58 mm Hg). The mean number of antiglaucoma medication prior to surgery was 3.1±0.4. By the end of the 12 months, IOP in all patients was reduced to normal level (13±1 mm Hg) and their antiglaucoma medication was decreased to 0.8±1.1. No recurring attack of glaucomatocyclitic crisis occurred. DISCUSSION: In addition to oral valganciclovir therapy, trabectome surgery seems to be a reliable and effective tool for the management of glaucomatocyclitic crisis with uncontrolled IOP.

A controlled trial of oral acyclovir for iridocyclitis caused by herpes simplex virus. The Herpetic Eye Disease Study Group.

OBJECTIVE: To assess the benefit of adding oral acyclovir to a regimen of topical prednisolone phosphate and trifluridine for the treatment of iridocyclitis caused by herpes simplex virus (HSV). METHODS: Patients with HSV iridocyclitis were enrolled in a multicenter controlled clinical trial supported by the National Eye Institute, Bethesda, Md, and randomly assigned to receive a 10-week course of either oral acyclovir, 400 mg, 5 times daily, or oral placebo in conjunction with regimens of topical trifluridine and a topical corticosteroid. Follow-up examinations were performed weekly during the 10-week treatment period, every 2 weeks for an additional 6 weeks, and at 26 weeks after enrollment in the trial. Treatment failure was defined as a persistence or worsening of ocular inflammation, withdrawal of medication because of toxicity, or a request by the patient to withdraw from the trial for any reason. The trial was stopped because of slow recruitment after only 50 of the originally planned 104 patients were enrolled in more than 4 years. RESULTS: A treatment failure occurred in 11 (50%) of the 22 patients in the acyclovir-treated group and in 19 (68%) of the 28 patients in the placebo group. Compared with the placebo group, the adjusted rate ratio for a treatment failure in the acyclovir-treated group during the 10-week treatment period was 0.43 (90% confidence interval, 0.18-1.02; P = .06, 1-tailed) and during the 16-week follow-up period (10-week treatment period plus 6-week observation period) was 0.60 (90% confidence interval, 0.29-1.25; P = .13, 1-tailed in a proportional hazards model). The treatment effect seemed slightly greater when only the patients with a persistence or worsening of ocular HSV disease were considered as treatment failures (ie, excludes terminations because of toxic effects of the drug and patients who requested to withdraw from the trial). By life-table analysis, similar results were obtained; the possible benefit of acyclovir became apparent after the first 3 weeks of follow-up. CONCLUSION: While the number of patients recruited in this trial was too small to achieve statistically conclusive results, the trend in the results suggests a benefit of oral acyclovir in the treatment of HSV iridocyclitis in patients receiving topical corticosteroids and trifluridine prophylaxis.