Collarette Elimination and Demodex Mite Eradication with Topical Lotilaner Ophthalmic Solution, 0.25.

Purpose: To evaluate the efficacy of topical lotilaner ophthalmic solution, 0.25%, in patients with Demodex blepharitis. Methods: Eighteen adults with Demodex blepharitis, defined as >10 collarettes on the upper lid and/or mite density of ≥1.5 mites per lash (upper and lower), were treated bid for 42 days with the topical lotilaner ophthalmic solution, 0.25%. Contact lens wear, artificial eyelashes, and lid structural abnormalities were among the exclusion criteria. No other antibacterial, antiparasitic, or anti-inflammatory treatment or lid hygiene products were permitted. One eye of each patient was selected for analysis and assessed on day 7, 14, 28, and 42. Collarettes were graded at each visit, and mite density was evaluated by microscopy at each visit except day 7. Outcome measures were collarette elimination (≤2 lashes with collarettes) and mite eradication (0 mites). Drop tolerability, adverse events, visual acuity, and slit-lamp biomicroscopy were assessed. Results: Collarette elimination was achieved in 13/18 participants (72.2%) by day 42. Mean collarette grade (upper lid) declined from 3.56 ± 0.17 to 0.28 ± 0.11. Mite eradication was achieved in 14/18 participants (77.8%) by day 42. Mean mite density decreased from 2.63 ± 0.39 to 0.12 ± 0.08 mites/lash. Participants reported good tolerability. Adverse events were mild and transient and did not result in treatment discontinuation. Conclusion: Six weeks of at-home topical therapy with the lotilaner ophthalmic solution, 0.25%, was effective in eliminating the most common objective signs of Demodex blepharitis, with a collarette elimination rate of 72% and mite eradication in 78% of eyes by day 42. ISRCTN registration #: 24398865.

The effect of lid hygiene on the tear film and ocular surface, and the prevalence of Demodex blepharitis in university students.

AIM: To evaluate the effect blepharitis lid cleansers have on the tear film and ocular surface, and to examine the prevalence of Demodex folliculorum in a young population. METHODS: Forty-eight university students completed a randomised, controlled, investigator-masked, eight-week clinical trial. Three eyelid hygiene products were investigated: blepharitis eyelid cleanser (OCuSOFT® Lid Scrub® PLUS foam), diluted baby shampoo (10% Johnson's® No More Tears ®) and a tea-tree based face wash (dr.organic®). Cooled boiled water was used as a control. Subjects attended for four visits: baseline, two weeks, four weeks and eight weeks. At each visit, subjective symptoms, non-invasive tear break up time, ocular surface staining and Demodex folliculorum investigation were assessed to evaluate any positive or negative effect on the tear film and ocular surface. Osmolarity was also measured at baseline and week eight only. RESULTS: The overall prevalence of Demodex folliculorum found at baseline was 15%. Subjective symptoms improved in all groups, including control. There was no significant difference in mean osmolarity between the groups or within each group after eight weeks. There was a significant increase in osmolarity inter-eye variability in the baby shampoo group (5.5 ±â€¯5.4 vs 15.2 ±â€¯9.5; p = 0.03). There was no significant change in non-invasive tear break up time or ocular surface staining demonstrated after eight weeks of eyelid hygiene. CONCLUSION: A low prevalence of Demodex folliculorum can be found in a young population. All blepharitis lid cleansers used demonstrated subjective improvement in symptoms, with no negative effects on tear break-up time or ocular surface staining. The blepharitis eyelid cleanser and tea-tree based face wash revealed no adverse effect on mean osmolarity or inter-eye variability. Similarly, baby shampoo did not cause a significant increase in mean osmolarity, however, a significant increase in inter-eye variability was found; suggesting a possible increase in ocular surface inflammation.

Ice compresses aid the reduction of swelling and pain after scleral buckling surgery.

AIMS AND OBJECTIVES: To investigate the therapeutic effects of a local ice compress in alleviating eyelid swelling and errhysis and providing relief from pain after surgery. BACKGROUND: Eyelid swelling and pain are the most common postoperative symptoms after scleral buckling surgery. A local ice compress can reduce the severity of swelling, errhysis and pain after acute injury as well as after surgery. DESIGN: A retrospective study. METHODS: A total of 100 patients who had undergone scleral buckling surgery for retinal detachment were classified into an ice compress group or a control group. All patients received standard postoperative medical care: a 1% Tropicamide ophthalmic solution (Minims® Tropicamide; Bausch & Lomb, Surrey, UK), a 1% prednisolone acetate (Pred-Forte; Allergan, Irvine, CA, USA), an ophthalmic tobramycin 0·3%/dexamethasone 0·1% combination ointment (Tobradex® ; Alcon, Fort Worth, Texas, USA) and 0·5% Levofloxacin eye drops (Santen Pharmaceutical, Osaka, Japan), plus a homemade ice pack was placed over the operated eye of patients in the ice compress group for 30 minutes, three times a day for two consecutive postoperative days. RESULTS: The severity of swelling, pain and errhysis in the operated eyes was significantly lower in the ice compress group. CONCLUSIONS: The local ice compress therapy helped reduce swelling, errhysis and pain in the operated eye after scleral buckling surgery. RELEVANCE TO CLINICAL PRACTICE: Use of a local ice compress after scleral buckling surgery can reduce swelling and pain on operated eyes, providing greater comfort for patients.

Incidence, recurrence, and outcomes of herpes simplex virus eye disease in Olmsted County, Minnesota, 1976-2007: the effect of oral antiviral prophylaxis.

OBJECTIVES: To provide an estimate of the incidence of herpes simplex virus (HSV) eye disease in a community-based cohort, and to investigate the effect of prophylactic oral antiviral therapy on HSV recurrences and outcomes. METHODS: All Olmsted County, Minnesota, residents diagnosed with ocular HSV from 1976 through 2007 were retrospectively reviewed. The frequency of recurrences and adverse outcomes, such as vision loss or need for surgery, were compared between untreated patients and those treated prophylactically with oral antiviral medication. RESULTS: Three hundred ninety-four patients with ocular HSV were identified, yielding an annual incidence of 11.8 per 100,000 people (95% confidence interval [CI], 10.6-13.0). No trends in incidence or adverse outcomes were identified during the 32-year period. Oral antiviral therapy was prescribed in 175 patients. Patients were 9.4 times more likely (95% CI, 5.0-17.9) to have a recurrence of epithelial keratitis, 8.4 times more likely (95% CI, 5.2-13.7) to have a recurrence of stromal keratitis, and 34.5 times more likely (95% CI, 10.8-111.1) to have a recurrence of blepharitis or conjunctivitis if not being treated prophylactically at the time of the recurrence. Twenty patients experienced adverse outcomes, and 17 (85%) were not being treated with oral antiviral medications immediately preceding the adverse event. CONCLUSIONS: Oral antiviral prophylaxis was associated with a decreased risk of recurrence of epithelial keratitis, stromal keratitis, conjunctivitis, and blepharitis due to HSV. Patients with adverse outcomes due to ocular HSV were usually not being treated with oral antiviral prophylaxis.

Switching from a preserved to a preservative-free prostaglandin preparation in topical glaucoma medication.

PURPOSE: The purpose of this study was to investigate the tolerability and intraocular pressure (IOP) reducing effect of the first preservative-free prostaglandin tafluprost (Taflotan) in patients exhibiting ocular surface side-effects during latanoprost (Xalatan) treatment. METHODS: A total of 158 patients were enrolled in this open-label multicentre study. Eligible patients had to have at least two ocular symptoms, or one sign and one symptom, during treatment with latanoprost. At baseline, the patients were directly switched from latanoprost to preservative-free tafluprost for 12 weeks. The patients were queried for ocular symptoms, and ocular signs were assessed by using tear break-up time, Schirmer's test, fluorescein staining and evaluation of conjunctival hyperaemia and blepharitis. In addition, HLA-DR and MUC5AC in conjunctival impression cytology specimens were analyzed, and a drop discomfort/quality of life (QoL) questionnaire was employed. IOP was measured at all visits. RESULTS: Preservative-free tafluprost maintained IOP at the same level after 12- weeks treatment (16.4 +/- 2.7 mmHg) as latanoprost at baseline (16.8 +/- 2.5 mmHg). During treatment with preservative-free tafluprost, the number of patients having irritation/burning/stinging (56.3%), itching (46.8%), foreign body sensation (49.4%), tearing (55.1%) and dry eye sensation (64.6%) decreased to 28.4%, 26.5%, 27.1%, 27.1% and 39.4% correspondingly. The number of the patients with abnormal fluorescein staining of cornea (81.6%) and conjunctiva (84.2%), blepharitis (60.1%), conjunctival hyperaemia (84.2%) and abnormal Schirmer's test (71.5%) was also reduced significantly to 40.6%, 43.2%, 40.6%, 60.0% and 59.4% correspondingly. The tear break-up time improved significantly from 4.5 +/- 2.5 seconds to 7.8 +/- 4.9 seconds. A reduction in the number of patients with abnormal conjunctival cells based on HLA-DR and MUC5AC was also detected. CONCLUSIONS: Preservative-free tafluprost maintained IOP at the same level as latanoprost, but was better tolerated in patients having signs or symptoms while on preserved latanoprost. Preservative-free tafluprost treatment resulted in improved QoL, increased patient satisfaction and drop comfort.

Involvement of STAT4 in IgG subtype switching and ocular HSV-1 replication in mice.

PURPOSE: To assess the relative impact of elevated T-helper 2 (T(H)2)- and reduced T-Helper 1 (T(H)1)-dependent immune responses on ocular herpes simplex virus type 1 (HSV-1) infection. METHODS: Signal transducer and activator of transcription protein 4 knockout mice (BALB/c-STAT4(-/-)) and wild-type BALB/c control mice were immunized with avirulent HSV-1 strain KOS or were mock-immunized. Three weeks after the third immunization, neutralizing antibody titers were determined by plaque reduction assays. Following ocular infection with virulent HSV-1 strain McKrae, viral replication in the eye, blepharitis, corneal scarring (CS), survival, and immunoglobulin (Ig) isotypes in sera were determined. RESULTS: Vaccinated STAT4(-/-) and BALB/c mice contained significant and similar neutralizing antibody titers and were completely protected against HSV-1-induced death and CS. In contrast to vaccinated STAT4(-/-) mice, mock-vaccinated STAT4(-/-) mice had higher ocular HSV-1 titers than mock-vaccinated BALB/c mice on days 2-3 post-ocular infection. There were also significant differences in the levels of IgG2a, IgG2b, and IgG3 in the sera of STAT4(-/-) mice when compared to the control BALB/c mice. CONCLUSIONS: These results suggest that the absence of T(H)1 cytokine responses did alter protection against viral replication and IgG isotypes but not eye disease or survival.

Soft contact lens use for upper eyelid surgery.

PURPOSE: To evaluate the usefulness of silicone hydrogel soft contact lenses in upper eyelid procedures. METHODS: Thirteen patients (14 eyes) who had full thickness upper lid reconstruction were studied. PureVision contact lenses were placed on the eyes at the commencement of the surgery. To evaluate the effectiveness of soft contact lens use, we looked at comfort, conjunctival injection, chemosis, corneal abrasion, lid oedema, evidence of infection and speed of healing. RESULTS: Nine eyes (64.29 per cent) were entirely asymptomatic. Three eyes developed corneal abrasions and changing the contact lenses led to resolution of the symptoms. One eye developed cloudy vision at one week due to accumulation of discharge behind the contact lens and another eye had foreign body sensation. Both had immediate relief with contact lenses removal. Mean duration of contact lens wear was 19.5 days (range, seven to 35 days). There were no cases of chemosis, infection, unexplained post-operative inflammation or delayed wound healing. CONCLUSIONS: Despite its limitations, our study suggests that a soft contact lens may be a useful option in upper lid surgery.

Macrophages are important determinants of acute ocular HSV-1 infection in immunized mice.

PURPOSE: To determine the effect of macrophage depletion on herpes simplex virus type (HAV)-1 replication in the eye and on the establishment of latency in trigeminal ganglia (TG) of immunized and ocularly infected mice. METHODS: BALB/c mice were immunized with five HSV-1 glycoprotein DNA genes or were sham immunized. The virulent HSV-1 strain KOS was used as a positive vaccine control. Immunized mice were depleted of their macrophages by dichloromethylene diphosphonate (Cl(2)MDP) injection. After ocular infection with the HSV-1 strain McKrae, virus replication in the eye, blepharitis, corneal scarring, and dermatitis were determined. Finally, the copy numbers of latency-associated transcript (LAT) and CD4(+) and CD8(+) T-cell transcripts in the TGs of surviving mice 30 days after infection were determined by RT-PCR. RESULTS: Depletion of macrophages in immunized mice increased HSV-1 replication in the eye of infected mice between days 1 and 5 after ocular infection. Depletion of macrophages did not alter the HSV-1-induced death or corneal scarring in immunized mice. Macrophage depletion, however, resulted in increased blepharitis in immunized mice. Finally, macrophage depletion had no effect on the establishment of latency in immunized mice, as the TGs from both depleted and mock-depleted mice were negative for the presence of the LAT transcript. CONCLUSIONS: In immunized mice during primary HSV-1 ocular infection, macrophages play an important role in vaccine efficacy against HSV-1 replication in the eye and blepharitis in infected mice. During the latent stage of HSV-1 infection, however, macrophage depletion failed to have any observable effect on HSV-1 latency in the TGs of infected mice.

Cyclosporin A inhibits eosinophilic infiltration into the conjunctiva mediated by type IV allergic reactions.

BACKGROUND: Eosinophils are important effector cells in severe allergic conjunctivitis such as vernal keratoconjunctivitis. Infiltration of eosinophils into the conjunctiva is mediated by type I and type IV allergic reactions. Cyclosporin A (CsA) eye drops are administered therapeutically for severe allergic conjunctivitis, but the mechanism by which CsA acts, that is, by inhibiting type I, type IV or both types of allergic reactions, is not known. We investigated whether CsA eye drops inhibit type I, type IV or both types of allergic reactions in the conjunctiva. METHODS: Experimental immune-mediated blepharoconjunctivitis (EC) was induced in BALB/c mice by either active immunization or passive immunization by transfer of ragweed (RW)-primed splenocytes and RW-specific IgE, followed by RW challenge to the conjunctiva. These mice were treated in eye drops with vehicle, 0.1% CsA, 0.5% CsA or 0.1% betamethasone five times (1 and 2 h before RW challenge and 1, 2 and 3 h after RW challenge). Twenty-four hours after the challenge, the conjunctivas were harvested for histological analysis to evaluate eosinophilic infiltration. To evaluate effects of CsA eye drops on systemic immune responses, sera and spleens were collected from actively immunized mice at the time of sacrifice to examine serum IgE levels and cellular immune responses, respectively. RESULTS: CsA eye drops significantly inhibited eosinophilic infiltration into the conjunctiva in actively immunized EC-developing mice compared with vehicle-treated mice. The CsA-induced inhibition was similar to inhibition induced by 0.1% betamethasone. Serum IgE levels and splenocyte responses in CsA-treated mice were equivalent to those in vehicle-treated mice. Betamethasone treatment inhibited eosinophilic infiltration into the conjunctiva induced by both splenocyte transfer and IgE transfer, while CsA treatment inhibited infiltration induced by splenocyte transfer. CONCLUSIONS: CsA eye drops inhibited eosinophilic infiltration into the conjunctiva without affecting systemic immune responses. CsA predominantly inhibits eosinophilic infiltration by interfering with the type IV allergic reaction in the conjunctiva.

Artificial tears inhibit the development of experimental immune-mediated blepharoconjunctivitis.

PURPOSE: To investigate whether treatment with artificial tears inhibits the development of experimental immune-mediated blepharoconjunctivitis (EC). METHODS: Brown Norway rats were immunized with ovalbumin (OVA) or ragweed (RW) emulsified in complete Freund's adjuvant. Fourteen days after immunization, the rats were challenged with the same antigen (Ag) in eye drops. Treated rats were administered artificial tears by eye drops immediately after, 15 min after, or 30 min after the Ag challenge. Treatment doses of 2, 4, or 8 drops per eye were evaluated. Twenty-four hours after the Ag challenge, the rats were killed and their eyes were harvested for histological studies. RESULTS: Treatment with artificial tears immediately after and 15 min after challenge with partially insoluble RW Ag suppressed infiltration of inflammatory cells into the conjunctiva. Inhibition was not observed at any time following challenge with OVA Ag, which is a soluble protein. The treatment dose of artificial tears administered did not affect the extent of inhibition of EC following challenge with either Ag. CONCLUSIONS: Treatment with artificial tears by eye drops inhibited the development of EC induced by the partially insoluble RW Ag when administered within 15 min of the Ag challenge.

Improved protection from primary ocular HSV-1 infection and establishment of latency using multigenic DNA vaccines.

PURPOSE: To compare the effectiveness of immunization with "naked" DNA corresponding to the genes encoding five HSV-1 glycoproteins, gB, gC, gD, gE, and gI (5gP DNA), with immunization with the five glycoproteins (5gP protein). Also, to compare immunization of 5gP protein in Montanide ISA 720 (SEPPIC, Paris, France), an adjuvant recently approved for use in humans, with immunization of 5gP protein in Freund's adjuvant. METHODS: BALB/c mice were vaccinated with 5gP DNA or 5gP protein emulsified in ISA 720 or Freund's adjuvant. Neutralizing antibody titers were determined by plaque-reduction assays. IL-2, -4, and -12 and IFN-gamma levels were determined by ELISA after in vitro stimulation of spleen cells. After ocular challenge with 2 x 10(5) plaque-forming units [pfu] per eye of HSV-1 strain McKrae, virus replication in the eye, survival, blepharitis, corneal scarring, and latency were determined. RESULTS: Neutralizing antibody titers (approximately 1:800-1:1200), corneal scarring (trace) and survival (100%) were similar for all vaccine groups, including 5gP DNA. Compared with the other vaccine groups, the 5gP DNA group had less ocular virus replication, as judged both by maximum virus titer and time of viral clearance. ISA 720 appeared more effective than Freund's against ocular virus replication and eye disease. The 5gP DNA-vaccinated mice had less blepharitis and latency than any other group and had the highest levels of IL-12 and IFN-gamma. All vaccine groups had similar levels of IL-2. CONCLUSIONS: The 5gP DNA vaccine appeared to be more effective than the corresponding protein subunit vaccine, regardless of adjuvant. Emulsification of the 5gP protein in ISA 720 appeared to be more effective than emulsification in Freund's adjuvant.

Long-term acyclovir use to prevent recurrent ocular herpes simplex virus infection.

OBJECTIVE: To evaluate the effectiveness of more than 12 months of oral acyclovir therapy in reducing recurrences of ocular herpes simplex virus. METHODS: We retrospectively compared ocular herpes simplex virus recurrence in 2 groups of patients. In group 1, patients used oral acyclovir for at least 12 months and then discontinued the treatment. In group 2, patients received the treatment for at least 18 months. We compared recurrences when both groups were using acyclovir (period 1) and when only group 2 was receiving the drug (period 2). Statistical analysis was performed with the t test, chi2 test, and Kaplan-Meier method. RESULTS: Group 1 had 18 patients and a mean +/- SD follow-up of 45.2 +/- 22.2 months. Group 2 had 22 patients and a mean +/- SD follow-up of 42.4 +/- 30.2 months. Six patients (33%) in group 1 and 4 patients (18%) in group 2 had recurrence in period 1 (P =.3). In period 2, 14 patients (78%) in group 1 and 8 patients (36%) in group 2 had recurrence (P =.01). Mean +/- SD recurrence-free survival in period 2 was 15.3 +/- 5.5 months in group 1 and 37.3 +/- 6.3 months in group 2 (P =.001). CONCLUSIONS: Long-term oral acyclovir use seems to remain effective in decreasing the number of ocular herpes simplex virus recurrences beyond 12 months.

Enhanced clearance of herpes simplex virus type 1 and reduced herpetic eye disease in STAT6 knockout mice is associated with increased IL-2.

STAT6 (signal transducers and activators of transcription 6)-deficient (STAT6-/-) mice have defects in IL-4- and IL-13-mediated functions and thus have a reduced T(H)2-mediated immune response. Conversely, they have elevated levels of IL-2 and thus an increased T(H)1-mediated immune response. To assess the relative impact of reduced T(H)2- and elevated T(H)1-dependent immune responses on HSV-1 infection, vaccinated and mock-vaccinated STAT6-/- mice were challenged ocularly with HSV-1. Mock-vaccinated STAT6-/- mice were as susceptible to lethal HSV-1 infection as parental BALB/c mice. Mock-vaccinated STAT6-/- mice had reduced HSV-1 titers in their eyes compared to BALB/c mice. Furthermore, mock-vaccinated STAT6-/- mice had significantly less corneal scarring than their BALB/c counterparts. Vaccination induced significantly higher serum-neutralizing antibody titers in STAT6-/- mice compared to BALB/c mice, while completely protecting both types of mice against HSV-1-induced death and corneal scarring. Vaccinated STAT6-/- mice had reduced HSV-1 titers in their eyes compared to BALB/c mice. Lymphocytes from both vaccinated and mock-vaccinated STAT6-/- mice secreted higher amounts of IL-2 than lymphocytes from BALB/c mice, in the presence or absence of stimulation with UV-inactivated HSV-1. Finally, depletion of IL-2 increased ocular virus replication in STAT6-/- mice to levels similar to that measured in BALB/c mice. Our results suggest that in the absence of the STAT6 pathway, IL-2-mediated immune responses are up-regulated. This, in turn, leads to faster viral clearance and, consequently, lower levels of eye disease.

Inhibitory effects of FK506 on the development of experimental allergic/immune-mediated blepharoconjunctivitis in Lewis rats by systemic but not by topical administration.

BACKGROUND: FK506 has been used for treatment of cell-mediated immune disorders such as graft rejection in transplantation or Behçet disease. To evaluate the effectiveness of FK506 in another ocular disease model, we injected FK506 in rats with experimental allergic/immune-mediated blepharo conjunctivitis (EAC) the induction mechanism of which depends on cell-mediated immunity. METHODS: Lewis rats were immunized with ovalbumin (OVA) in emulsion of complete Freund's adjuvant (CFA). We injected 2 (n = 6), 20 (n = 6) or 200 (n = 5) microg of FK506 intramuscularly daily from the day of immunization (day 0) to day 6. Control rats were not treated with FK506 (n = 4). In addition, we injected 200 microg of FK506 from day 7 to day 13 (n = 12) to compare the timing of FK506 administration (day 0 to day 6, n = 12; control, n = 12). Twenty-one days after immunization, all rats were challenged with OVA by eye drops, and 24 h later they were killed after clinical evaluation and their eyes, blood and draining lymph nodes were harvested for histology, antibody titers and proliferation assay or flow cytometric analysis. In another set of experiments, rats that had received OVA-primed lymph node cells did (n = 9) or did not (n = 9) receive additional FK506 by injection daily for 4 days. Four days after transfer, these rats were challenged with OVA and evaluated as mentioned. To investigate possible suppression of disease by topical administration of FK506, both actively immunized and passively immunized rats received OVA together with 0.3% (weight/volume) of FK506 (n = 16) or vehicle (n = 10) by eye drops and 24 h after challenge, rats were evaluated as mentioned. RESULTS: Development of disease, induced by either active or passive immunization, was inhibited in the group treated with 200 microg of FK506, regardless of timing of administration. Cellular proliferative responses to OVA were inhibited only in this group. Flow cytometry demonstrated a decrease of about 20% in the proportion of all cells made up by CD4-positive T cells. Topical administration of FK506 inhibited the development of EAC, though not significantly. CONCLUSIONS: Systemic treatment with 200 microg of FK506 either in the induction or the effector phase inhibits the development of EAC in Lewis rats. Topical administration is not so effective as systemic administration.

Acyclovir for the prevention of recurrent herpes simplex virus eye disease. Herpetic Eye Disease Study Group.

BACKGROUND: Long-term treatment with antiviral agents has been shown to prevent recurrences of genital and orofacial herpes simplex virus (HSV) disease, but it is uncertain whether prophylactic treatment can prevent recurrences of ocular HSV disease. METHODS: We randomly assigned 703 immunocompetent patients who had had ocular HSV disease within the preceding year to receive 400 mg of acyclovir or placebo orally twice daily. The study outcomes were the rates of development of ocular or nonocular HSV disease during a 12-month treatment period and a 6-month observation period. RESULTS: The cumulative probability of a recurrence of any type of ocular HSV disease during the 12-month treatment period was 19 percent in the acyclovir group and 32 percent in the placebo group (P<0.001). Among the 337 patients with a history of stromal keratitis, the most common serious form of ocular HSV disease, the cumulative probability of recurrent stromal keratitis was 14 percent in the acyclovir group and 28 percent in the placebo group (P=0.005). The cumulative probability of a recurrence of nonocular (primarily orofacial) HSV disease was also lower in the acyclovir group than in the placebo group (19 percent vs. 36 percent, P<0.001). There was no rebound in the rate of HSV disease in the six months after treatment with acyclovir was stopped. CONCLUSIONS: After the resolution of ocular HSV disease, 12 months of treatment with acyclovir reduces the rate of recurrent ocular HSV disease and orofacial HSV disease. Long-term antiviral prophylaxis is most important for patients with a history of HSV stromal keratitis, since it can prevent additional episodes and potential loss of vision.