Successful Management of Herpes Simplex Keratitis With Oral Valganciclovir in Patients Unresponsive or Allergic to Conventional Antiviral Therapy.

PURPOSE: To describe 4 cases of presumably immunocompetent patients with herpes simplex virus (HSV) keratitis unresponsive (n = 3) or allergic (n = 1) to conventional antiviral therapy that improved with oral valganciclovir treatment. METHODS: Retrospective case series of 4 patients with HSV keratitis treated with oral valganciclovir between March 2016 and June 2018. RESULTS: We reviewed the records of 4 patients with recurrent epithelial HSV keratitis. Three patients were on antiviral prophylaxis because of a history of HSV keratitis. All patients were on oral acyclovir, valacyclovir, and/or famciclovir treatment with/without topical antiviral therapy for 4 to 6 months for prophylaxis and/or recurrent dendriform epithelial keratitis. While 3 patients had recurrent episodes during their active prophylaxis with oral antiviral therapies, one patient had a recurrence after she discontinued her oral prophylactic antiviral therapy due to recurrent self-reported allergic reactions. The patients presented with recurrent dendriform epithelial keratitis despite conventional antiviral therapy. We initiated oral valganciclovir 900 mg twice a day for 10 days as a treatment dose, followed by 900 mg daily for prophylaxis. The corneal epithelium subsequently healed within the first 2 weeks in all patients. The mean follow-up time for patients on valganciclovir prophylaxis was 8 months (range: 6-12 months), and none of the patients presented with any further recurrences. CONCLUSIONS: In case of treatment-related side effects or failure with conventional antiviral therapies, oral valganciclovir may present an alternative for the treatment and prophylaxis of HSV keratitis.

Perinatal photoperiod imprints the circadian clock.

Using real-time gene expression imaging and behavioral analysis, we found that the perinatal photoperiod has lasting effects on the circadian rhythms expressed by clock neurons as well as on mouse behavior, and sets the responsiveness of the biological clock to subsequent changes in photoperiod. These developmental gene × environment interactions tune circadian clock responses to subsequent seasonal photoperiods and may contribute to the influence of season on neurobehavioral disorders in humans.

Population encoding by circadian clock neurons organizes circadian behavior.

Mammalian circadian rhythms are orchestrated by the suprachiasmatic nuclei (SCN) of the hypothalamus. The SCN are composed of circadian clock neurons, but the mechanisms by which these populations of neuronal oscillators encode rhythmic behavior are incompletely understood. We have used ex vivo real-time gene expression imaging of the neural correlates of circadian behavior, combined with genetic disruption of vasoactive intestinal polypeptide, a key SCN signaling molecule, to examine the neural basis of circadian organization in the SCN. We show that the coherence and timing of clock neuron rhythms are correlated with the coherence and timing of behavioral rhythms within individual mice and that the degree of disruption of SCN neuronal organization correlates with the degree of behavioral disruption within individuals. Our results suggest that the SCN encode circadian phase as a temporal population vector of its constituent neurons; such that as the neuronal population becomes desynchronized, phase information becomes ambiguous.