Ocular Herpes Simplex Research Articles

OCULAR HERPES SIMPLEX INFECTIONS IN CHILDREN

A survey of "hospitalised" Herpes simplex infections in otherwise normal healthy children under the age of 13 years over a 15 year period between 1964 and 1979 at Princess Margaret Hospital for Children. This survey highlighted the unnecessarily high transference rate of Herpes simplex virus (HSV) infection to the under 3 year old within the home environment. There were three hundred and forty (340) cases of non-fatal "hospitalized" HSV infections in the under 3 year old of which sixty three (63) were ocular infections. Over all age groups one hundred and forty five (145) children were hospitalised on one or several occasions with ocular HSV infection. Of these children before reaching the age of 13 years, fifteen (15) developed intraocular HSV infection and twenty seven (27) had a permanent visual acuity of less than 6/12. As a result of this survey the Princess Margaret Hospital motto for the I.Y.D.P. is: "Cuddle but do not kiss your child when you have an acute coldsore"

An Increase in Herpes Simplex Virus Type 1 in the Anterior Segment of the Eye Is Linked to a Deficiency in NK Cell Infiltration in Mice Deficient in CXCR3

In response to ocular herpes simplex virus type 1 (HSV-1) infection in mice, a rapid induction or increase in the local expression of chemokines, including CXCL10, is found. The present study investigated the role of the receptor for CXCL10, CXCR3, in the host response to corneal HSV-1 infection. Mice deficient in CXCR3 (CXCR3(-/-)) were found to have an increase in infectious virus in the anterior segment of the eye by day 7 postinfection. Coinciding with the increase, selective chemokines, including CCL2, CCL3, CCL5, CXCL9, and CXCL10, were elevated in the anterior segment of the HSV-1-infected CXCR3(-/-) mice. In contrast, there was a time-dependent reduction in the recruitment of natural killer (NK) cells (NK1.1(+)CD3(-)) into the anterior segment of CXCR3(-/-) mice. A reduction in NK cells residing in the anterior segment of mice following antiasialoGM1 antibody treatment resulted in an increase in infectious virus. No other leukocyte populations infiltrating the tissue were modified in the absence of CXCR3. Collectively, the loss of CXCR3 expression specifically reduces NK cell mobilization into the cornea in response to HSV-1.

Laser in situ keratomileusis in patients with a history of ocular herpes

To report the outcomes of laser in situ keratomileusis (LASIK) in patients with a history of ocular herpes simplex virus (HSV) or herpes zoster ophthalmicus (HZO). Clínica Baviera, Instituto Oftalmológico Europeo, Madrid, Spain. In this retrospective case series, the records of eyes with a history of ocular herpes that had LASIK from 2003 through 2005 were reviewed. The main outcome measure was postoperative recurrence of ocular herpes. Forty-nine eyes (48 patients) with a history of ocular herpes (HSV keratitis, 28 eyes; HSV eyelid lesions, 17 eyes; HZO, 4 eyes) were identified. All LASIK procedures were uneventful. Herpetic disease was inactive at the time of surgery in all eyes and for more than 1 year in 31 eyes. Perioperative antiviral systemic prophylaxis was used in 13 patients with a history of HSV keratitis. No eye developed reactivation of herpetic keratitis during the follow-up (range 1 to 28 months). Laser in situ keratomileusis was safe in patients with a history of ocular herpes; no recurrences occurred during the follow-up period. However, candidates should be selected with caution and surgery performed only in eyes in which the herpes has been inactive for 1 year before surgery, without stromal disease, and with regular topography and pachymetry maps and normal corneal sensitivity. The most reasonable clinical strategy is perioperative systemic antiviral prophylaxis.

Lactoferrin Glu561Asp polymorphism is associated with susceptibility to herpes simplex keratitis

Lactoferrin plays an important role in the defense against infections, including herpes simplex virus (HSV) keratitis. We studied the impact of three single nucleotide polymorphisms in the human lactoferrin gene on the susceptibility to HSV infections of the eye and the severity of such infections. Lactoferrin gene polymorphisms were determined by PCR combined with restriction fragment length analysis in 105 HSV keratitis patients and 145 control subjects. Bilateral tear samples were harvested from 50 patients and 40 healthy controls and tear lactoferrin concentrations were determined by ELISA. Patients' records were used to acquire information about the severity of the HSV keratitis. The frequencies of the Glu561Asp polymorphism, but not those of the Ala11Thr and Lys29Arg polymorphisms, differed significantly between patients and control subjects with an under-representation of the Asp561 allele in the patient group. Furthermore, the values for best corrected visual acuity, frequency of recurrences since onset, and average duration of clinical episodes did not differ among patients with various lactoferrin genotypes. In addition, tear lactoferrin concentrations were the same in patients with HSV keratitis and healthy controls and also did not differ among patients with various lactoferrin genotypes. Lactoferrin Glu561Asp polymorphism is associated with the susceptibility to HSV keratitis with a protective role for lactoferrin variants comprising Asp561. However, no beneficial effects of this lactoferrin variant on the clinical outcome of ocular HSV keratitis were noted.

Protective Immunity against Ocular Herpes Infection and Disease Induced by Highly Immunogenic Self-Adjuvanting Glycoprotein D Lipopeptide Vaccines

An important phase in the development of an ocular herpes simplex virus type 1 (HSV-1) subunit vaccine is the identification of an efficient, safe, and adjuvant-free antigen delivery system capable of inducing and sustaining long-term memory T-cell protective immunity. This study was conducted to test the hypothesis that immunization with self-adjuvanting lipopeptide bearing HSV-1 glycoprotein D (gD) T-cell epitopes would elicit long-term HSV-specific T cells and decrease infection, disease, or both in a ocular herpes mouse model. Five immunodominant CD4(+) T-cell peptide epitopes (gD(1-29), gD(49-82), gD(146-179), gD(228-257), and gD(332-358)), recently identified from HSV-1 gD, were covalently linked to a palmitic acid moiety (lipopeptides) and delivered subcutaneously in adjuvant-free saline. The primary and memory T cells induced by these molecularly defined lipopeptides and their protective efficacy were assessed, in terms of virus replication in the eye, ocular disease, and survival. Three gD lipopeptides, that drive dendritic cell maturation in vitro, induced long-term, virus-specific, IFN-gamma-producing CD4(+) Th(1) responses, associated with a reduction in ocular herpes infection and disease. Immunization with a cocktail of these three highly immunogenic Th(1) lipopeptides increased survival, lowered the peak of ocular virus titer, and cleared the ocular disease. Vaccination with a mixture self-adjuvanting lipopeptides containing novel HSV-1 immunodominant gD T-cell epitopes protected mice from ocular herpes infection and disease. The strength of protective immunity induced by these lipopeptides together with their safety provide a molecularly defined vaccine formulation that could combat ocular herpes infection and disease in humans.

Efficacy of Valacyclovir vs Acyclovir for the Prevention of Recurrent Herpes Simplex Virus Eye Disease: A Pilot Study

To compare the efficacy of one-year treatment with valacyclovir vs acyclovir in preventing recurrence of the herpes simplex virus (HSV) eye disease. Prospective, randomized, clinical trial pilot study. Fifty-two immunocompetent patients with a history of recurrent ocular HSV disease were treated at the Ocular Immunology Service, San Raffaele Hospital, Milan, Italy. Twenty-six patients were randomized to the valacyclovir group (one 500 mg tablet daily), and 26 patients were randomized to the acyclovir group (one 400 mg tablet twice daily). The recurrence rate of ocular HSV disease during 12 months of treatment and drug-related side effects were monitored. Recurrence of any type of ocular HSV disease during the 12-month treatment period was 23.1% in the valacyclovir group, compared with 23.1% in the acyclovir group. No difference between the two groups was observed regarding the nature, frequency, or severity of adverse events. The most frequent adverse events were nausea and headache. One-year suppression therapy with oral valacyclovir (500 mg tablet daily) was shown to be as effective and as well tolerated as acyclovir (400 mg tablet twice daily) in reducing the rate of recurrent ocular HSV disease.

Herpes Simplex Keratitis After Intravitreal Triamcinolone Acetonide

To report a case of recurrent herpes simplex virus (HSV) epithelial keratitis after intravitreal triamcinolone acetonide injection for the treatment of diabetic macular edema. Case report. We describe a case of a 59-year-old woman with a history of ocular HSV disease and severe proliferative diabetic retinopathy. She received an intravitreal injection of triamcinolone acetonide for macular edema in the right eye. One week later, she developed foreign body sensation, redness, and photophobia in the same eye. Slit-lamp examination revealed a corneal epithelial dendritic lesion. She was diagnosed with a recurrence of HSV epithelial keratitis and was treated with oral acyclovir 400 mg, 5 times a day, with good resolution of HSV signs and symptoms. Intravitreal triamcinolone acetonide injection may result in reactivation of HSV keratitis.

IL-10 and natural regulatory T cells: two independent anti inflammatory mechanisms in HSV induced ocular immonopathology (B63)

Abstract Our past studies have shown a protective role for both CD4+CD25+Foxp3+ natural regulatory T cells (nTregs) as well as IL-10 in Herpes Simplex Virus (HSV) induced Stromal Keratitis (SK). Among several other mechanisms, IL-10 has been shown to be involved in the nTreg mediated suppression. We have shown in vitro that blocking of IL-10 could partially block the Treg mediated suppression of activated effectors isolated from SK lesions. But it is not known whether in the in vivo conditions, IL-10 and nTreg influence the SK pathology independently or in concert. Interestingly, IL-10−/− animals depleted of nTregs prior to ocular HSV infection had more severe SK lesion as compared to undepleted IL-10−/− animals. These results show the presence of two independent anti inflammatory mechanisms in SK. Along this line, by using mice expressing GFP-Foxp3 we could not show CD4+GFP-Foxp3+IL-10+ cells in the DLNs and spleens of infected wild-type (WT) mice although animals depleted of nTregs had higher levels of IL-10 in the DLNs post infection. Furthermore, by using WT, IL-10−/− and nTreg depleted WT and IL-10−/− animals we have compared the relative importance of IL-10 and nTregs in reducing SK pathology. Although disease severity was significantly higher in IL-10−/− and both the nTreg depleted groups as compared to WT, highest severity was found in the IL-10−/− mice depleted of nTregs. Intracellular cytokine staining with UV-HSV and polyclonal stimulation of the cells isolated from infected corneas, DLN and spleens revealed that IL-10 has more profound anti inflammatory effects in SK as compared to nTregs and that the later could act in an IL-10 independent manner.

Epithelial Herpetic Simplex Keratitis Recurrence and Graft Survival After Corneal Transplantation in Patients With and Without Atopy

To compare the incidence of herpes simplex virus (HSV) epithelial recurrence and graft survival after penetrating keratoplasty (PK) in patients with and without self-reported atopy. Retrospective cohort comparative study. Cornea Service, Wills Eye Hospital. Patients who presented with previously diagnosed ocular HSV between March 2003 and March 2004 and who underwent primary PK for ocular HSV at the Cornea Service. From the 58 patients invited, 49 patients (50 eyes) were included. Nine patients were ineligible in accordance with the exclusion criteria: no active classic HSV episode before PK, immunosuppression, less than one year of follow-up, previous history of PK before presentation at the Service. Eligible patients filled out a questionnaire regarding their history of atopic disease, considering: presence of allergic rhinitis, asthma, or atopic dermatitis. Ocular history was obtained through chart review. main outcome measures: Incidence of epithelial HSV recurrences and corneal graft survival in both groups. Each group (atopic and nonatopic) included 25 eyes. The atopic patients had a mean incidence of 0.07 episode/eye year (SD +/- 0.9) compared with 0.12/eye year (standard deviation [SD] +/- 0.21) in the nonatopics (P = .002). At 10 years of follow-up, the survival rate in the atopics was of 92% and in the nonatopics was of 79% (P = .88). Nonatopics had significantly more epithelial recurrences after PK compared to atopics; however, both groups presented low incidences of recurrences and high graft survival rates.

Role of Stat4-Mediated Signal Transduction Events in the Generation of Aggressor CD4+T Cells in Herpetic Stromal Keratitis Pathogenesis

Ocular infection with herpes simplex virus (HSV) causes a vision-impairing inflammatory reaction called herpetic stromal keratitis. In murine models, herpetic stromal keratitis lesions appear to be immunopathologic, mediated by CD4(+) T cells of Th1 phenotype. To provide insight about cytokine networks and signaling events involved in the development of aggressor CD4(+) T cells, ocular HSV infection was followed in mice deficient in Stat4 (Stat4(-/-) mice), the signal transducer for the cytokine interleukin-12 (IL-12). After ocular HSV infection of Stat4(-/-) and control BALB/c mice, clinical, histologic, and immunologic analyses were carried out. Further, to evaluate the involvement of Stat4 in the development of this aggressor population, naive CD4(+) T cells from Stat4(-/-) and BALB/c mice were adoptively transferred to C.B-17 SCID mice 1 day after corneal infection. Although Stat4(-/-) mice demonstrated increased susceptibility to lethal encephalitis and facial lesions, interestingly, these mice had less severe stromal keratitis in comparison to control animals. Adoptive transfer of naive CD4(+) T cells from Stat4(-/-) mice failed to produce disease in infected SCID recipients. The data imply a significant role of Stat4-mediated signaling events in the generation of an aggressor CD4(+) T cell population in stromal keratitis pathogenesis.

Comparative Study of Ocular Herpes Simplex Virus in Patients With and Without Self-Reported Atopy

Comparative Study of Ocular Herpes Simplex Virus in Patients With and Without Self-Reported Atopy

Efficacy of Oral Antiviral Prophylaxis in Preventing Ocular Herpes Simplex Virus Recurrences in Patients With and Without Self-Reported Atopy

To compare the efficacy of oral antiviral prophylactic treatment for herpes simplex virus (HSV) recurrences in patients with and without self-reported atopy. Retrospective cohort comparative study. setting: Cornea Service, Wills Eye Hospital. study population: Patients who presented with previously diagnosed ocular HSV between March 2003 and March 2004. From 244 patients invited, 54 patients (58 eyes) were included. One hundred and ninety patients were excluded according to exclusion criteria: no active episode during follow-up, immunosuppression, less than one year of follow-up, or previous history of penetrating keratoplasty. The Questionnaire regarding history of atopic disease, considers: presence of allergic rhinitis, asthma or atopic dermatitis, and chart review of ocular history. main outcome measures: Incidence of all types of HSV recurrences with and without antiviral prophylaxis within each group and between groups. HSV episodes were classified into infectious, inflammatory, and mixed for analysis. Atopic/nonatopic (P value): mean follow-up without prophylaxis 8.1 (+/- 8.2)/7.3 years (+/- 8.6) (P = .71); mean follow-up with prophylaxis 2.9 (+/- 2.3)/2.6 years (+/- 2.2) (P = .51); the effect of prophylaxis significantly reduced the all recurrences in both groups except in the inflammatory recurrences in the atopic group and in the mixed recurrences in both groups. Prophylaxis decreased infectious episodes by 44% in nonatopic and 76% in atopics and decreased inflammatory manifestations by 69% in the nonatopic group and 8% in the atopic group. Antiviral prophylaxis for HSV recurrences was more effective in reducing infections in atopics and less effective in reducing inflammatory episodes in atopics versus nonatopics.

Comparative Study of Ocular Herpes Simplex Virus in Patients With and Without Self-Reported Atopy

To compare the characteristics of ocular herpes simplex virus (HSV) in patients with and without atopy. Retrospective cohort comparative study. Patients who presented at the Cornea Service, Wills Eye Hospital, between March 2003 and March 2004 who had been previously diagnosed in the same institution as having ocular HSV diagnosis or were just diagnosed as having the disease were asked to complete a study questionnaire that enabled categorization into atopic and nonatopic. In April 2005, 223 patients who agreed to be in the study had their charts reviewed, and 125 patients were excluded according to exclusion criteria: immunosuppression, follow-up less than one year, previous history of penetrating keratoplasty (PK) out of the Cornea Service, and no active HSV episode during follow-up. Incidence of all types of HSV recurrences. Bilaterality, visual loss, need for PK , and secondary bacterial infection in both groups. HSV episodes were classified into infectious, inflammatory, and mixed for analysis. Ninety eight patients (110 eyes) were included in the study. Atopic/nonatopic (P value): the mean follow-up was 11.6 (+/- 10.6)/8.8 years (+/- 8.4) (P = .14); the mean incidence of HSV episodes per year of follow-up was: total episodes 0.32 (+/- 0.36)/0.28 (+/- 0.33) (P = .14), infectious 0.16 (+/- 0.22)/0.10 (+/- 0.14) (P < .01), inflammatory 0.11 (+/- 0.19)/0.11 (+/- 0.19) (P < .01), and mixed 0.09 (+/- 0.20)/0.07 (+/- 0.16) (P = .06); bilateral HSV was present in 9/3 patients (P = .22); the mean loss of vision was four lines of Snellen in both groups; PK was performed in 14 of 16 eyes (P = .45); secondary bacterial infection was present in two of four eyes (P = .26). Atopic patients had considerably more infectious and fewer inflammatory episodes when compared with nonatopics.

Abnormal immune response of CCR5-deficient mice to ocular infection with herpes simplex virus type 1.

Ocular herpes simplex virus type 1 (HSV-1) infection elicits a strong inflammatory response that is associated with production of the beta chemokines CCL3 and CCL5, which share a common receptor, CCR5. To gain insight into the role of these molecules in ocular immune responses, the corneas of wild-type (WT) and CCR5-deficient (CCR5-/-) mice were infected with HSV-1 and inflammatory parameters were measured. In the absence of CCR5, the early infiltration of neutrophils into the cornea was diminished. Associated with this aberrant leukocyte recruitment, neutrophils in CCR5-/- mice were restricted to the stroma, whereas in WT mice, these cells trafficked to the stroma and epithelial layers of the infected cornea. Virus titres and cytokine/chemokine levels in the infected tissue of these mice were similar for the first 5 days after infection. However, by day 7 post-infection, the CCR5-/- mice showed a significant elevation in the chemokines CCL2, CCL5, CXCL9 and CXCL10 in the trigeminal ganglion and brainstem, as well as a significant increase in virus burden. The increase in chemokine expression was associated with an increase in the infiltration of CD4 and/or CD8 T cells into the trigeminal ganglion and brainstem of CCR5-/- mice. Surprisingly, even though infected CCR5-/- mice were less efficient at controlling the progression of virus replication, there was no difference in mortality. These results suggest that, although CCR5 plays a role in regulating leukocyte trafficking and control of virus burden, compensatory mechanisms are involved in preventing mortality following HSV-1 infection.

Ocular Herpes Simplex: Changing Epidemiology, Emerging Disease Patterns, and the Potential of Vaccine Prevention and Therapy

To review the changing epidemiology of herpes simplex virus infection, emerging patterns of herpetic ocular disease, and the challenges and promise of herpes simplex virus vaccine therapy. Perspective. Literature review. An epidemic increase in genital herpes simplex type 2 infection is reflected in a 30% increase in HSV-2 antibodies in the United States since 1976. Approximately one in four people in the United States over age 30 is infected with HSV-2. Primary acquisition of herpes simplex type 1 is becoming progressively delayed in many industrialized countries, in contrast to developing nations where the virus is acquired early in life and is ubiquitous. Changes in sexual behavior among young adults have been associated with a recent increase in genital HSV-1 infection, resulting from oral-genital rather than genital-genital contact. Clinical trials of HSV vaccines using selected herpes simplex virus type 2 proteins mixed in adjuvant have shown limited efficacy in seronegative women, but not in men. The recent epidemic of genital herpes simplex type 2 infection is likely to result in an increase in neonatal ocular herpes and in delayed cases of acute retinal necrosis syndrome. The increase in genital HSV-1 may lead to industry production of vaccines that contain components of both HSV-1 and HSV-2 targeted toward limiting genital disease and transmission. As newer herpes simplex vaccines become available, ophthalmologists must be vigilant that a boost in immunity against HSV does not have a paradoxical effect in exacerbating break-through cases that develop immune-mediated herpes simplex stromal keratitis.

The effects of aminoguanidine on primary and recurrent ocular herpes simplex virus infection

In primary ocular herpes simplex virus (HSV) infection, nitric oxide may function to control viral replication and herpetic stromal keratitis (HSK) lesions. Recurrent HSK, manifested as corneal opacity and neovascularization, is the potentially blinding sequel to primary infection. Here, we assess the effects of nitric oxide synthase inhibition on a mouse model of recurrent HSK. In preliminary primary infection experiments, NIH inbred mice treated with aminoguanidine, an inhibitor of inducible nitric oxide synthase (iNOS), experienced no changes in post-infection tear, brain, or ganglia virus titers, but encephalitis-related mortality was elevated. After UV-B stimulated viral reactivation, iNOS inhibition did not affect virus shedding or clinical disease. In contrast to primary HSK, there was no exacerbation of mortality in recurrent disease. Our findings indicate that nitric oxide can be neuroprotective without antiviral effects in primary HSK, and does not play a significant role in the pathogenesis of recurrent HSK. Compared with data from other mouse strains, this work suggests that there may be a genetic component to the importance of NO in controlling ocular HSV infection.

In Vivo Kinetics of GITR and GITR Ligand Expression and Their Functional Significance in Regulating Viral Immunopathology

This report evaluates the role of interaction between glucocorticoid-induced tumor necrosis factor receptor (GITR) and GITR ligand (GITR-L) in the immuno-inflammatory response to infection with herpes simplex virus (HSV). Both GITR and GITR-L were transiently upregulated after ocular HSV infection, on antigen-specific T cells and antigen-presenting cells, respectively, in the draining lymph node (DLN). In addition, virus-specific T-cell responses in the DLN and spleen were enhanced by anti-GITR antibody treatment, an outcome expected to result in more severe inflammatory lesions. Intriguingly, the treatment resulted in significantly diminished T-cell-mediated ocular lesions. The explanation for these findings was that anti-GITR antibody treatment caused a reduced production of ocular MMP-9, a molecule involved in ocular angiogenesis, an essential step in the pathogenesis of herpetic keratitis. Our results are the first observations to determine in vivo kinetics of GITR and GITR-L expression after virus infection, and they emphasize the role of GITR-GITR-L interaction to regulate virus-induced immuno-inflammatory lesions.

Critical Role for the Oligoadenylate Synthetase/RNase L Pathway in Response to IFN-β during Acute Ocular Herpes Simplex Virus Type 1 Infection

We previously demonstrated that IFN-beta transgene treatment protects mouse trigeminal ganglia (TG) cells from acute HSV-1 infection in vitro. However, IFN-alpha6 transgene treatment does not provide protection against acute HSV-1 infection in vitro, even though equivalent levels of IFN are expressed with both transgene treatments. In the present study we show that IFN-beta transgene treatment before acute ocular HSV-1 infection protects mice from HSV-1-mediated mortality, whereas IFN-alpha6 transgene treatment does not reduce mortality. Treatment with the IFN-beta and IFN-alpha6 transgenes was associated with increased expression of oligoadenylate synthetase (OAS)1a mRNA in the eye. However, protein kinase R mRNA was not up-regulated in the eye. In TG, only IFN-beta transgene treatment reduced infectious virus levels. Furthermore, in the absence of a functional OAS pathway, corneal HSV-1 Ag expression was more widespread, and the ability of IFN-beta transgene treatment to reduce infectious HSV-1 in eyes and TG was lost. Along with selective up-regulation of OAS1a mRNA expression in TG from IFN-beta transgene-treated mice, we found increased levels of phospho-STAT1. Likewise, p38 MAPK phosphorylation was increased in TG from IFN-beta transgene-treated mice, compared with both IFN-alpha6 and vector-treated mice. We also observed a time-dependent increase in JNK phosphorylation in TG from IFN-beta transgene-treated vs IFN-alpha6 and vector-treated mice. Our results demonstrate that IFN-beta is a potent antiviral cytokine that exerts protection against ocular HSV-1 infection via selective up-regulation of OAS1a mRNA in TG and by altering the phosphorylation of proteins in antiviral signaling cascades.

Herpes Simplex Virus Keratitis After Laser in situ Keratomileusis

To report two cases of herpes simplex virus (HSV) keratitis after laser in situ keratomileusis (LASIK). Interventional small case series. Two patients underwent uneventful LASIK. History of herpes labialis in one patient and herpetic eye disease > 10 years prior to intervention in the other patient was reported. Both patients developed stromal herpetic keratitis 6 weeks and 2 years after the procedure, respectively. Treatment consisting of topical steroid drops and topical and systemic antiviral therapy was administered. Recurrences of the herpetic keratitis were seen after tapering of the topical steroids; four and three recurrences were observed, respectively. Final visual acuity was > 6/9 in both cases. Herpetic keratitis after LASIK is an uncommon, possibly under-reported, entity. Even patients without history of herpetic eye disease can present with this complication. Oral antiviral prophylaxis may be appropriate when performing LASIK on patients with a history of ocular or systemic HSV infection.

Association between ocular herpes simplex virus and topical ocular hypotensive therapy

The authors performed a population-based, retrospective, cohort study to determine if the use of particular ocular hypertensive therapies is associated with ocular herpes simplex virus (OHSV). An OHSV event was either a medical claim from the Protocare Sciences managed care database (United States) with an International Classification of Diseases Ninth Edition (ICD-9) code for OHSV or a pharmacy claim for vidarabine or trifluridine ophthalmic solution. A total of 93,869 eligible glaucoma patients, 21 different ocular hypotensive agents, and 192,840 agent-utilizing patient combinations were identified. The overall OHSV event rate was 0.11%. The prevalence rate was estimated to be 161 per 100,000 population for 2000 to 2001 and 165 per 100,000 population for 1999 and 2001. There was no significant association between OHSV events rates and agent use for either the set of 21 agents (P = .260) or when 14 products having <5% usage were combined (P = .058). The authors conclude that the prevalence of OHSV among patients using ocular hypotensive therapy is similar to that found in the general population and there is no association between any specific hypotensive agent and OHSV.—Michael D. Wagoner