Herpetic Eye Disease Study: A Controlled Trial of Topical Corticosteroids for Herpes Simplex Stromal Keratitis.

PURPOSE: To evaluate the efficacy of topical corticosteroids in treating herpes simplex stromal keratitis. METHODS: The authors performed a randomized, double-masked, placebo-con- trolled, multicenter clinical trial of 106 patients with active herpes simplex stromal keratitis who had not received any corticosteroids for at least 10 days before study enrollment. Patients were assigned to the placebo group (n = 49) or the steroid group (topical prednisolone phosphate; n = 57); both regimens were tapered over 10 weeks. Both groups received topical trifluridine. Visual acuity assessment and slit-lamp biomicroscopy were performed weekly for 10 weeks, every other week for an additional 6 weeks or until removal from the trial, and at 6 months after randomization. RESULTS: The time to treatment failure (defined by specific criteria as persistent or progressive stromal keratouveitis or an adverse event) was significantly longer in the steroid group compared with the placebo group. Compared with placebo, corticosteroid therapy reduced the risk of persistent or progressive stromal keratouveitis by 68%. The time from randomization to resolution of stromal keratitis and uveitis was significantly shorter in the steroid group compared with the placebo group even though both groups included patients who were removed from the study and treated with topical corticosteroids according to best medical judgment. Nineteen (33%) of the steroid-treated patients and 11 (22%) of the placebo-treated patients completed the 10 weeks of protocol therapy and had stable, noninflamed corneas after 16 weeks. At 6 months after randomization, no clinically or statistically significant differences in visual outcome or recurrent herpetic eye disease were identified between the steroid and placebo groups. CONCLUSIONS: The topical corticosteroid regimen used in this study was significantly better than placebo in reducing persistence or progression of stromal inflammation and in shortening the duration of herpes simplex stromal keratitis. Postponing steroids during careful observation for a few weeks delayed resolution of stromal keratitis but had no detrimental effect as assessed by visual outcome at 6 months.

Adenovirus advances: new diagnostic and therapeutic options.

PURPOSE OF REVIEW: Adenoviral infection is common, can be severe, and may cause significant morbidity. RECENT FINDINGS: Ophthalmologists and optometrists are often guilty of spreading adenovirus because it is highly contagious and has 53 serotypes with variable morphology. Adenovirus is often difficult to diagnose based on clinical appearance and, in the early stages, is associated with a red eye or superficial keratitis common to herpes and other infections. This difficulty results in the indiscriminate use of antibiotics, which are expensive and of no established value in treating a viral infection. The difficulty of accurate diagnosis also makes the use of newer proposed treatments less valuable and even potentially hazardous. SUMMARY: New diagnostic tests such as the Rapid Pathogen Screening (RPS) Adeno Detector that are practical, rapid, and inexpensive to use in the office may obviate these problems.

The high prevalence of herpes simplex virus type 1 DNA in human trigeminal ganglia is not a function of age or gender.

The purpose of this study was to determine the presence and copy numbers of herpes simplex virus type 1 (HSV-1) DNA in human trigeminal ganglia (TG) with respect to age, gender, and postmortem interval (PMI). Human TG (n = 174, obtained from the Oregon Brain Bank, with data on age, gender, and PMI) were analyzed for HSV-1 DNA copies (HSV-1 DNA polymerase gene) by using real-time PCR. We found that 89.1% (131/147) of subjects and 90.1% (155/174) of TG contained HSV-1 DNA. The copy numbers of HSV-1 DNA in the positives ranged from very high (>10(6)) to very low (5). These data confirm and strengthen our previous findings that subjects were positive for HSV-1 DNA in tears (46/50; 92%) and saliva (47/50; 94%). These TG data and tear and saliva data demonstrated considerable variability in copy numbers of HSV-1 DNA per subject. Statistical analysis showed no significant relationship between gender and copy number, age and copy number, or PMI and copy number for each pair of variables. A factorial analysis of gender, age, and PMI with respect to copy number also showed no statistical significance. This is the first study that provides statistical analysis that documents that the prevalence of HSV-1 DNA in the human TG is not a function of either gender or age.

Ocular HSV-1 latency, reactivation and recurrent disease.

Ocular infection with HSV-1 continues to be a serious clinical problem despite the availability of effective antivirals. Primary infection with HSV-1 can involve ocular and adenaxial sites and can manifest as blepharitis, conjunctivitis, or corneal epithelial keratitis. After initial ocular infection, HSV-1 can establish latent infection in the trigeminal ganglia for the lifetime of the host. During latency, the viral genome is retained in the neuron without producing viral proteins. However, abundant transcription occurs at the region encoding the latency-associated transcript, which may play significant roles in the maintenance of latency as well as neuronal reactivation. Many host and viral factors are involved in HSV-1 reactivation from latency. HSV-1 DNA is shed into tears and saliva of most adults, but in most cases this does not result in lesions. Recurrent disease occurs as HSV-1 is carried by anterograde transport to the original site of infection, or any other site innervated by the latently infected ganglia, and can reinfect the ocular tissues. Recurrent corneal disease can lead to corneal scarring, thinning, stromal opacity and neovascularization and, eventually, blindness. In spite of intensive antiviral and anti-inflammatory therapy, a significant percentage of patients do not respond to chemotherapy for herpetic necrotizing stromal keratitis. Therefore, the development of therapies that would reduce asymptomatic viral shedding and lower the risks of recurrent disease and transmission of the virus is key to decreasing the morbidity of ocular herpetic disease. This review will highlight basic HSV-1 virology, and will compare the animal models of latency, reactivation, and recurrent ocular disease to the current clinical data.

Efficacy of a helicase-primase inhibitor in animal models of ocular herpes simplex virus type 1 infection.

PURPOSE: The aim of this study was to evaluate the effect of BAY 57-1293, a helicase-primase inhibitor, on herpes simplex virus type 1 (HSV-1) reactivation in mice and its efficacy on established disease in rabbits. METHODS: BALB/c mice latent for McKrae-strain HSV-1 were reactivated via heat stress, treated with BAY 57-1293, and their corneas were swabbed for virus or the trigeminal ganglia (TG) obtained for quantification of viral DNA. New Zealand white rabbits were infected and treated topically or orally in comparison with trifluridine or valacyclovir. RESULTS: Oral BAY 57-1293 suppressed reactivation in HSV-1-infected mice and reduced the viral load in TG up to four orders of magnitude. In the rabbits, the therapeutic efficacies of topical BAY 57-1293 and trifluridine were similar. Once-daily oral BAY 57-1293 was significantly more effective than valacyclovir and as effective as twice a day topical trifluridine. CONCLUSIONS: BAY 57-1293 may be more effective than valacyclovir, without the cytotoxicity or potential healing retardation seen with trifluridine. Oral BAY 57-1293 may be a substitute for eye drops as an effective treatment for herpetic keratitis and might be useful in treating stromal keratitis and iritis, as well as preventing recurrences of ocular herpes.

Clinical corneal confocal microscopy.

Confocal microscopy allows non-invasive in vivo imaging of the ocular surface. Its unique physical properties enable microscopic examination of all layers of the cornea and have been used to investigate numerous corneal diseases: epithelial changes, numerous stromal degenerative or dystrophic diseases, endothelial pathologies, corneal deposits, infections, and traumatic lesions. It offers a new approach to study the physiological reactions of the cornea to different stimuli and the pathophysiologic events leading to corneal dysfunction in certain diseases. Confocal microscopy proves to be a powerful diagnostic tool and is especially of value in certain corneal diseases by allowing straightforward and non-invasive recognition of the pathologic conditions.

The use of the Fugo Blade in corneal surgery: a preliminary animal study.

PURPOSE: To evaluate the performance of the Fugo Blade in cutting corneal tissue in animals, both in vitro and in vivo. METHODS: Corneal incisions were made on pig eyes using the Fugo Blade. The histologic characteristics of these cuts were then evaluated. Similar cuts were also performed in rabbit corneas in vivo and compared with cuts performed with mechanical blades. The rabbits were euthanized, and the corneas were obtained for histopathologic examination 14 days after surgery. RESULTS: Slit-lamp examinations and histologic findings showed that the Fugo Blade can produce sharp cuts in the cornea with minimal tissue damage beyond the edges of the incisions. It cuts without resistance and permits normal wound healing. CONCLUSIONS: Although the Fugo Blade is currently approved by the Food and Drug Administration for anterior capsulotomy, our study demonstrates that the Fugo Blade can safely and quickly produce resistance-free cuts in corneal tissue in animals, opening additional avenues for use of this device in corneal surgery.

Healing process at the flap edge in its influence in the development of corneal ectasia after LASIK.

PURPOSE: Post-laser in situ keratomileusis (LASIK) corneal ectasia is a progressive deformation of the gross corneal anatomy that occurs after surgery. However, this is a rare event even after deep lamellar keratoplasty. We hypothesize that the strength of the lamellar keratoplasty wound is derived from the sutures that enhance the wound edge healing response. This study compares, in a rabbit model, the stability of previously sutured and unsutured microkeratome flaps. METHODS: Unilateral 160-micro m-thick LASIK flaps using a mechanical microkeratome was performed in 20 rabbit eyes. Animals were then divided in two groups: In group A, the flap was left without sutures. In group B, the flap was sutured with 12 interrupted 10/0 nylon stitches that were removed after 3 weeks under general anesthesia. Six weeks after surgery, all rabbits had corneal topographies performed at their baseline intraocular pressure (IOP) (14 mmHg) and at two artificially increased pressures (25 and 45 mmHg) using an anterior chamber maintainer implanted in the inferior limbal area. The animals were humanely euthanized, and immunohistological analysis of the corneas was performed. RESULTS: A delta K1 value, which indicates the difference in the simulated keratometric value at baseline and the one measured at 25 mmHg, was calculated for all eyes. It showed a mean steepening effect of 2.74 D +/- 0.38 D in group A compared with 1.08 D +/- 0.27 D in group B (p < 0.05). Similarly, a delta K2 value, which indicates the difference in the simulated keratometric value at baseline and the one obtained at 45 mmHg, was registered. It showed a mean steepening effect of 3.02 D +/- 0.87 D in group A compared with 0.75 D +/- 0.44 D in group B (p < 0.05). Six weeks after surgery, the peripheral flap interface in group B consisted of 14.3% +/- 4.15% of positive monoclonal mouse anti-alpha smooth muscle actin (alpha-SMA) cells compared with 4.18 +/- 3.76% in group A (p < 0.05). CONCLUSIONS: The addition of sutures in the corneal flap after LASIK appears to reduce the amount of corneal steepening when the IOP is artificially increased up to 25 mmHg in this rabbit model. Our results suggest that an increase in the amount of myofibroblastas induced by the sutures may be responsible for this behavior. Corneal ectasia may be related to the clinically observed lack of corneal wound-healing at the edge of the flap that allows the cornea to bulge. By stimulating a stronger wound-healing response at the edge of the flap, the cornea may better resist steepening under increased IOP conditions and improve the long-term stability of LASIK surgery in borderline thin corneas.

A new surgical technique for anterior segment ectasia: tectonic lamellar sclerokeratoplasty.

A 41-year-old patient with severe anterior segment ectasia and a previous history of failed corneal graft was treated by placing a 14-mm tectonic corneoscleral allograft in the eye to support both the corneal and the scleral thinning. Nylon 10-0 interrupted sutures were used at the sclero-scleral junction. The host conjunctiva, including the limbal area, was carefully sutured to the donor limbal area. Three months postoperatively, the graft was stable with no progression of the ectasia. The suturing of a corneoscleral graft over a severely ectatic cornea may be an acceptable technique for providing tectonic tissue support and stabilizing eyes with severe anterior segment ectasia.

Clinical outcomes of combined versus separate carbachol and brimonidine drops in correcting presbyopia.

BACKGROUND: To test and compare in a masked fashion the efficacy of using a parasympathomimetic drug (3% carbachol) and an alpha-2 agonist (0.2% brimonidine) in both combined and separate forms to create optically beneficial miosis to pharmacologically improve vision in presbyopia. METHODS: A prospective, double-masked, randomized, controlled clinical trial was conducted. Ten naturally emmetropic and presbyopic subjects between 42 and 58 years old with uncorrected distance visual acuity of at least 20/20 in both eyes without additional ocular pathology were eligible for inclusion. All subjects received 3% carbachol and 0.2% brimonidine in both combined and separate forms, 3% carbachol alone and 0.2% brimonidine (control) alone in their non-dominant eye in a crossover manner with one week washout between tests. The subjects' pupil sizes and both near and distance visual acuities will be evaluated pre- and post-treatment at 1, 2, 4, and 8 h, by a masked examiner at the same room illumination. RESULTS: Statistically significant improvement in mean near visual acuity (NVA) was achieved in all subjects who received combined 3% carbachol and 0.2% brimonidine in the same formula compared with those who received separate forms or carbachol alone or brimonidine alone (P < 0.0001). CONCLUSION: Based on the data, the combined solution demonstrated greater efficacy than the other solutions that were tested. Improving the depth of focus by making the pupil small caused statistically significant improvement in near visual acuity, with no change in binocular distance vision. TRIAL REGISTRATION: ACTRN12616001565437. Registered 11 November 2016.

HSV-1 DNA in tears and saliva of normal adults.

PURPOSE: To assess the frequency of shedding of herpes simplex virus type 1 (HSV-1) DNA in tears and saliva of asymptomatic individuals. METHODS: Fifty subjects without signs of ocular herpetic disease participated. Serum samples from all subjects were tested for HSV IgG antibodies by enzyme-linked immunosorbent assay (ELISA) and for HSV-1 by neutralization assay. HSV-1 DNA copy number and frequency of shedding were determined by real-time polymerase chain reaction (PCR) analysis of tear and saliva samples collected twice daily for 30 consecutive days. RESULTS: Thirty-seven (74%) of the 50 subjects were positive for HSV IgG by ELISA. The percentages of positive eye and mouth swabs were approximately equivalent: 33.5% (941/2806) and 37.5% (1020/2723), respectively. However, the percentage of samples with high HSV-1 genome copy numbers was greater in saliva than in tears, which may have been a result of the sample volume collected. Shedding frequency in tears was nearly the same in men (347/1003; 34.6%) and women (594/1705; 34.8%); in saliva, men had a higher frequency of shedding (457/1009; 45.3% vs. 563/1703; 33.1%, men versus women). Overall, 49 (98%) of 50 subjects shed HSV-1 DNA at least once during the course of the 30-day study. CONCLUSIONS: The percentage of asymptomatic subjects who intermittently shed HSV-1 DNA in tears or saliva was higher than the percentage of subjects with positive ELISA or neutralization antibodies to HSV. Because most HSV transmission occurs during asymptomatic shedding, further knowledge of the prevalence of HSV-1 DNA in tears and saliva is warranted to control its spread. Shedding is simple to study, and its suppression may be an efficient way to evaluate new antivirals in humans.

Topical tacrolimus ointment for treatment of refractory anterior segment inflammatory disorders.

PURPOSE: To report 4 cases of patients treated with topical tacrolimus ointment 0.03% for ocular inflammatory conditions refractory to traditional treatment. METHODS: Four patients were treated topically with tacrolimus 0.03% ointment twice daily: 2 patients with blepharokeratoconjunctivitis, 1 patient with severe atopic keratoconjunctivitis, and 1 patient with chronic follicular conjunctivitis. RESULTS: Three patients had a dramatic improvement of their ocular condition as early as 2 weeks after starting tacrolimus ointment. One patient developed a herpes simplex virus dendrite after 1 week of tacrolimus use. CONCLUSION: Tacrolimus ointment appears to be an effective alternative for certain ocular inflammatory conditions refractory to traditional treatments. There may be an increased risk of herpes simplex virus keratitis associated with topical use. Our results support previous literature of patients benefiting from topical tacrolimus use.

Preliminary in vitro evaluation of 2-octyl cyanoacrylate (Dermabond) to seal corneal incisions.

OBJECTIVE: To compare the efficacy of Dermabond with conventional nylon sutures for sealing linear corneal incisions. METHODS: A keratome knife was used to create a 4-mm full-thickness linear corneal incision anterior to the limbal arcade in 20 fresh pig eyes. The incision was sealed with Dermabond tissue adhesive or closed with 10-0 nylon sutures. A 27-gauge needle connected via tubing to a bottle containing balanced salt solution (BSS) was inserted into the anterior chamber. Infusion pressure was controlled by varying the height of the column of BSS. The tensile strength of the incisions was measured by increasing the infusion pressure to the point where leakage was noted. RESULTS: The mean height at which leakage was detected was 100.20 +/- 31.19 cm H(2)O (equivalent to a pressure of 73.70 +/- 22.99 mm Hg) for the nylon suture group (n = 10 eyes) and 113.80 +/- 31.20 cm H(2)O (equivalent to a pressure of 83.71 +/- 22.95 mm Hg) for the Dermabond group (n = 10 eyes). The difference was not significant (P = 0.343). CONCLUSIONS: The mean leakage pressures were comparable for the 2 groups. Either method of closure should be able to withstand any postoperative increases in intraocular pressure. Dermabond adhesive may be considered as an alternative to conventional sutures in corneal wound closure.

Immunohistochemical analysis of orbital connective tissue specimens of patients with active Graves ophthalmopathy.

PURPOSE: To explore the immune mechanism of Graves ophthalmopathy (GO) by analyzing infiltrating cells in orbital connective tissue (OCT) specimens of patients with active GO using immunohistochemical methods. METHODS: Five OCT specimens obtained from patients with active GO and five control specimens obtained from forensic cadavers who died from nonmedical reasons were stained with anti-CD3, CD4, CD8, CD45RO, HLA-Dr, CD25, and TNF-alpha monoclonal antibodies. Positively stained cells were counted and results were interpreted as cell counts/mm2. Four of five GO patients had never been treated with any immunomodulating therapy. Only one had received oral prednisolone prior to tissue sampling, but this treatment had ceased 5 months before surgery. RESULTS: The retro-orbital tissue specimens obtained from forensic cadavers did not show any significant positive staining for any monoclonal antibody tested. However, the specimens from GO patients showed positively stained means of 36.66 +/- 4.61 HLA-Dr+, 12.8 +/- 3.42 CD8+, 11.8 +/- 1.78 CD4+, 16.6 +/- 1.81 CD3+, 21.2 +/- 3.12 CD45RO+, 10.4 +/- 2.07 TNF-alpha+, 7.2 +/- 1.48 CD25+, 3.2 +/- 1.09 CD4+CD8+, 4.6 +/- 1.67 CD4+CD45RO+, 2.8 +/- 0.83 CD8+CD45RO+, 1.6 +/- 0.89 CD4+CD25+, and 1.8 +/- 1 0.83 CD8+CD25+ cells/mm2. CONCLUSIONS: Our study supports that most of the infiltrating lymphocytic cells in the active stage of GO are T cells, and a significant proportion of them are CD45RO+ cells. Infiltration of OCT by HLA-Dr+, CD25+, and TNF-alpha cells suggests that Th1-type immune reaction with the interference of proinflammatory cytokine(s) (TNF-alpha) may be important in the pathogenesis of disease. Further studies are needed to understand the disease pathogenesis and may provide a scientific basis for future treatment alternatives for the disease (e.g., anti-cytokine treatment).

Inhibition of cyclooxygenase 2 synthesis suppresses Herpes simplex virus type 1 reactivation.

Recurrent herpes virus infection, in which the virus reactivates from the nervous system and causes painful lesions in peripheral tissues, is a significant clinical problem. Our recent studies showing that the amount of cyclooxygenase 2 (COX-2) in the trigeminal ganglia of heat-stressed untreated mice is higher than the amount in heat-stressed mice treated with the COX-2 inhibitor, celecoxib, have indicated that the prostaglandin synthesis pathway--and in particular COX-2--may be an intermediate in the pathway to herpes viral reactivation. To further study this process, we infected the corneas of mice using topical application to a lightly scratched epithelium and waited 30 days for Herpes simplex virus type 1 (HSV-1) latency to be established in the trigeminal ganglia. Prior to the induction of viral reactivation, the mice were treated orally with celecoxib. Treated and untreated mice were induced to undergo reactivation by immersion in 43 degrees C water for 10 min. The shedding of virus at the ocular surface was determined by culturing ocular swabs with indicator cells. The presence of infectious virus in the trigeminal ganglion was evaluated by incubating ganglion homogenates with indicator cells and observing for cytopathic effect. Celecoxib treatment significantly suppressed viral reactivation when given prophylactically by the gastrointestinal route. The numbers of corneas and ganglia containing infectious virus were significantly lower in the celecoxib-treated animals, compared to the placebo-treated mice. These experiments demonstrate that a selective COX-2 inhibitor can suppress hyperthermic stress-induced herpes viral reactivation in the nervous system. It may be possible to use COX-2 inhibitors to prevent viral reactivation in high-risk patients by drug prophylaxis.

Corneal healing after uncomplicated LASIK and its relationship to refractive changes: a six-month prospective confocal study.

PURPOSE: To investigate corneal healing and the factor(s) possibly responsible for refractive changes after laser in situ keratomileusis (LASIK). METHODS: Twenty eyes of 10 patients who underwent LASIK for myopia were examined clinically and by real-time confocal microscopy for 6 months. Epithelial and posterior stromal thicknesses and the thickness of the keratocyte activation zone were measured, and refractive changes were compared with these values. Keratocyte morphology, flap thickness, and subbasal nerve fiber bundle morphology after LASIK were also investigated. RESULTS: No significant change was detected over time in epithelial thickness after LASIK treatment; however, the posterior stromal thickness was found to be significantly higher 1 month after surgery. A slight but statistically significant negative correlation was detected between the thickness of the keratocyte activation zone and the spheroequivalent refraction after LASIK. The subbasal nerve fiber bundle's morphology returned to its preoperative appearance 6 months after LASIK, but in the flap stroma the nerve fiber bundle morphology remained abnormal at 6 months after LASIK surgery. CONCLUSIONS: A weak but significant negative correlation between the thickness of the keratocyte activation zone and spheroequivalent refraction was found after LASIK. The different refractive properties of activated keratocytes may be responsible for the myopic shift after LASIK. Further studies are needed to clarify this hypothesis.

The comparison of efficacies of topical corticosteroids and nonsteroidal anti-inflammatory drops on dry eye patients: a clinical and immunocytochemical study.

PURPOSE: To investigate whether conjunctival inflammation represents a primary event in the pathogenesis of keratoconjunctivitis sicca or whether it is a secondary inflammatory reaction caused by enhanced mechanical irritation as a result of surface dryness and whether anti-inflammatory drops (corticosteroids and nonsteroidal anti-inflammatory) have therapeutic effects and are similar. DESIGN: Single-masked, randomized, prospective clinical trial. METHODS: Thirty-two keratoconjuctivitis patients with or without Sjögren syndrome were included in the study. The patients were randomized to three groups. Group 1 patients received a topical artificial tear substitute (ATS); group 2 received ATS plus nonsteroidal anti-inflammatory drops (NSAID); and group 3 received ATS plus topical corticosteroidal drops. The eye symptom severity scores, Schirmer test values, rose bengal and fluorescein staining scores were evaluated before treatment and 15 and 30 days after start of treatment. Impression cytology specimens were stained using immunohistochemical methods to detect the percentages of human leukocyte antigen II (HLA-DR) positive, Apo 2.7 positive, and periodic acid-Schiff positive cells. Statistical analyses were performed within and between groups. Group 3 patients had significantly lower symptom severity scores, fluorescein and rose bengal staining, and HLA-DR positive cells on days 15 and 30 compared with patients in other groups. They also had a significantly higher number of periodic acid-Schiff positive (goblet) cells in their impression cytology specimens on days 15 and 30 compared with the other patients. On day 30, group 3 patients had significant differences compared with their baseline measurements in terms of above-mentioned parameters. However, we did not detect a significant effect of any treatment schedule on the Shirmer test value and the numbers of Apo 2.7 cells in impression cytology specimens. CONCLUSION: Topical corticosteroids had a clearly beneficial effect both on the subjective and objective clinical parameters of moderate-to-severe dry eye patients. These effects were associated with the reduction of inflammation markers of conjunctival epithelial cells.

Human fibrin tissue glue for corneal lamellar adhesion in rabbits: a preliminary study.

PURPOSE: To evaluate the use of a human fibrin tissue adhesive in the adherence of corneal lamellar flaps in rabbit eyes. METHODS: Corneal flaps were made using a microkeratome in both eyes of six New Zealand white rabbits. In the right eyes, the flaps were glued with fibrin tissue adhesive; in the left eyes, flaps were allowed to heal without adhesive (controls). All eyes were treated with antibiotics and steroids once daily for 10 days. Slit-lamp biomicroscopy was performed 1 and 10 days after surgery. The rabbits with surviving flaps were euthanized and the corneas obtained for histopathologic examination 10 days after surgery. RESULTS: Slit-lamp examinations showed no interface deposits and no other signs of corneal toxicity. Histologically, a few inflammatory cells were seen in both the experimental and control eyes, and microscopic gapping and tissue debris were observed in three of the six control eyes. CONCLUSIONS: Human fibrin tissue glue was well tolerated in these eyes, with no or minimal corneal toxicity. Further studies are needed to determine the tensile strength of the adhesive bond in the cornea.

Acetylsalicylic acid reduces viral shedding induced by thermal stress.

PURPOSE: To investigate the effect of acetylsalicylic acid on ocular shedding of herpes simplex virus type 1 (HSV-1). MATERIALS AND METHODS: Mice that were latent for the McKrae strain of HSV-1 were treated with acetylsalicylic acid, a nonspecific inhibitor of cyclooxygenases, either prophylactically or at the time of heat stress-induced viral reactivation. The effect of the drug on viral shedding in the tear film, infectious virus in the cornea and trigeminal ganglion, and viral DNA in the cornea and trigeminal ganglion was determined. RESULTS: Acetylsalicylic acid inhibited heat stress-induced shedding of virus in the tears and reduced the numbers of corneal and trigeminal ganglion homogenates containing virus. Intraperitoneal therapeutic and oral prophylactic plus therapeutic treatments were similar in their ability to inhibit reactivation. CONCLUSIONS: The results indicate that a cyclooxygenase inhibitor such as acetylsalicylic acid can reduce recurrent viral infection in mice. These findings may implicate prostaglandins as agents in the viral reactivation process and suggest that therapy to suppress viral reactivation using nontoxic inhibitors of prostaglandin synthesis may be effective in humans.