Validity of Postmortem Glycated Hemoglobin to Determine Status of Diabetes Mellitus in Corneal Donors.

PURPOSE: To examine the stability of postmortem glycated hemoglobin (HbA1c) measurement and its relationship to premortem glycemia. METHODS: Postmortem blood samples were obtained from 32 donors (8 known diabetic) and shipped on ice to a central laboratory to examine the stability of HbA1c measurements during the first 9 postmortem days. Thirty-nine other suspected diabetic donors underwent comparison of premortem and postmortem HbA1c measurements. RESULTS: Postmortem HbA1c measurements remained stable after 9 postmortem days (all measurements within ±0.2% from baseline with a mean difference of 0.02% ± 0.10%). Of the premortem measurements obtained within 90 days before death, 79% were within ±1.0% of the postmortem measurements compared with 40% for measurements more than 90 days apart. Three of the postmortem HbA1c measurements exceeded 6.5% (considered a threshold for diabetes diagnosis), although the medical histories did not indicate any previous diabetes diagnosis. CONCLUSIONS: Postmortem HbA1c testing is feasible with current eye bank procedures and is reflective of glycemic control of donors during 90 days before death. HbA1c testing could potentially be a useful adjunct to review of the medical history and records for donor assessment for endothelial keratoplasty suitability and long-term graft success.

Electron beam radiation for conjunctival squamous carcinoma.

PURPOSE: To describe the authors' technique and preliminary results using electron beam radiation as rescue therapy for recalcitrant squamous cell carcinoma of the conjunctiva and cornea. METHODS: A retrospective review comprised of an interventional case series of patients with pathologically confirmed diagnosis of squamous cell carcinoma of the conjunctiva and cornea, who had failed multiple standard treatments and underwent electron beam radiation therapy. Outcomes, radiation-related complications, and adverse effects were documented. Mortality and local control rates were calculated by the Kaplan-Meier survival probability method. RESULTS: Eight patients met the inclusion criteria; of these, 6 (75%) were men and 2 (25%) were women, with ages ranging from 38 to 65 years (mean 50 years). One tumor (12.5%) was classified as T2N0M0, 6 (75%) were classified as T3N0M0, and one (12.5%) was classified as T4N0M0. Follow up from electron beam radiation therapy ranged from 3 to 72 months (mean 30.25 months). The most common side effect was erythema and edema of the eyelids with diffuse transient eyelash loss, seen in all patients. Tumor local control and regression after electron beam radiation therapy were noted in 6 patients (75%); recurrence was noted in 2. There was neither metastatic spread nor tumor-related deaths. CONCLUSIONS: The authors report a small case series where local tumor control was achieved with electron beam radiation therapy for recalcitrant squamous cell carcinoma of the conjunctiva and cornea. This approach may be considered for patients who fail conventional therapy.

Topical application of the cornea post-infection with plasmid DNA encoding interferon-alpha1 but not recombinant interferon-alphaA reduces herpes simplex virus type 1-induced mortality in mice.

A study was undertaken to compare the efficacy of recombinant interferon (rIFN)-alphaA to plasmid DNA encoding IFN-alpha1 against ocular herpes simplex virus type 1 (HSV-1) infection. The topical application of rIFN-alphaA (100-300 units/eye) onto the cornea of mice subsequently infected 24 h later with HSV-1 antagonized viral-induced mortality. The enhancement in cumulative survival in the rIFN-alphaA-treated mice correlated with a reduction of viral titers recovered in the eye and trigeminal ganglion (TG) at 3 and 6 days post-infection. The protective effect was site-specific such that when rIFN-alphaA was administered orally or intranasally, no efficacy against HSV-1 was observed. However, the protective effect was time-dependent. Specifically, when the rIFN-alphaA (100-1000 units/eye) was administered at 24 h post-infection, no protective effect was observed against HSV-1 compared to the vehicle-treated group. In contrast, plasmid DNA (100 microg/eye) containing the IFN-alpha1 transgene showed significant protection when topically applied 24 h post-infection. Although the transgene was found to traffic distal from the site of application (eye), including the trigeminal ganglion and the spleen where CD11b(+) and CD11c(+) cells express the transgene, the migration of the transgene did not correlate with efficacy. Collectively, the results suggest that naked DNA encoding type I IFN applied post-infection provides a greater degree of protection against ocular HSV-1 infection in comparison with recombinant protein effectively antagonizing viral replication and spread.

Effect of famciclovir on herpes simplex virus type 1 corneal disease and establishment of latency in rabbits.

Famciclovir (FCV) is efficacious in the treatment of acute herpes zoster and recurrent genital infections but has not been used to treat ocular herpes simplex virus (HSV) infections. We evaluated the efficacy of orally administered FCV in treating HSV-1 epithelial keratitis and determined its effects on the establishment of latency and subsequent reactivation. Rabbits were inoculated with HSV-1 strain 17 syn+ and treated twice daily with increasing concentrations of FCV (60 to 500 mg/kg of body weight). This resulted in a significant, dose-dependent improvement in keratitis scores, as well as prolonged survival. Regardless of the dose of drug used, all groups exhibited the high rates of spontaneous and induced reactivation characteristic of 17syn+. The efficacy of 250 mg of FCV per kg was also compared to topical treatment with 1% trifluorothymidine (TFT). Although TFT treatment was more effective at reducing eye disease, FCV-treated rabbits had a better survival rate. Real-time quantitative PCR analysis of rabbit trigeminal ganglia (TG) demonstrated that FCV significantly reduced the HSV-1 copy number compared to that after treatment with TFT or the placebo but not in a dose-dependent manner. In summary, oral FCV treatment significantly reduces the severity of corneal lesions, reduces the number of HSV-1 genomes in the TG, improves survival, and therefore may be beneficial in reducing the morbidity of HSV keratitis in the clinic.