Impact of herpetic stromal immune keratitis in corneal biomechanics and innervation.

PURPOSE: To study corneal innervation in eyes with history of herpetic keratitis and its correlation with corneal sensitivity and biomechanical properties. METHODS: A total of 56 eyes were included, of which 16 had a history of unilateral immune stromal herpetic keratitis, 16 were their contralateral eyes, and 20 were healthy controls. Structural analysis of corneal nerve plexus was performed by confocal microscopy. Biomechanical properties were measured with the Ocular Response Analyzer. Corneal sensitivity was assessed by contact (Cochet-Bonnet) and non-contact (Belmonte) esthesiometry. RESULTS: The eyes with a history of herpetic keratitis had reduced sensitivity for mechanical stimuli when compared to healthy eyes (1441.88 ± 83 ml/min vs. 67.9 ± 7.86 ml/min). Nerve fiber density in the corneas with a history of herpetic disease was lower (4.13 ± 2.19 U/image) than in the contralateral eyes (7.44 ± 2.9 U/image, p value = 0.01) and than in healthy controls (10.35 ± 2.01, p value < 0.0001). The best structural and functional correlation was established between the total length of nerves per section and mechanic threshold assessed by Belmonte esthesiometer (Coef. -0.58 p value < 0.0001) and between total length of nerves and corneal resistance factor (CRF) (Coef. -0.64, p value < 0.0001). CONCLUSIONS: The corneal sensitivity impairment in eyes with immune stromal herpetic keratitis can be explained by the loss of nerve fibers. Biomechanical corneal properties are affected as well. Corneal hysteresis (CH) and CRF are lower for the eyes with a history of herpetic keratitis, and also for the contralateral eye when compared to healthy controls.

Immunogenicity, transplacental transfer of pertussis antibodies and safety following pertussis immunization during pregnancy: Evidence from a randomized, placebo-controlled trial.

BACKGROUND: Pertussis immunization during pregnancy is recommended in many countries. Data from large randomized controlled trials are needed to assess the immunogenicity, reactogenicity and safety of this approach. METHODS: This phase IV, observer-blind, randomized, placebo-controlled, multicenter trial assessed immunogenicity, transplacental transfer of maternal pertussis antibodies, reactogenicity and safety of a reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap) during pregnancy. Women received Tdap or placebo at 27-36 weeks' gestation with crossover ≤ 72-hour-postpartum immunization. Immune responses were assessed before the pregnancy dose and 1 month after, and from the umbilical cord at delivery. Superiority (primary objective) was reached if the lower limits of the 95% confidence intervals (CIs) of the pertussis geometric mean concentration (GMC) ratios (Tdap/control) in cord blood were ≥ 1.5. Solicited and unsolicited adverse events (AEs) and pregnancy-/neonate-related AEs of interest were recorded. RESULTS: 687 pregnant women were vaccinated (Tdap: N = 341 control: N = 346). Superiority of the pertussis immune response (maternally transferred pertussis antibodies in cord blood) was demonstrated by the GMC ratios (Tdap/control): 16.1 (95% CI: 13.5-19.2) for anti-filamentous hemagglutinin, 20.7 (15.9-26.9) for anti-pertactin and 8.5 (7.0-10.2) for anti-pertussis toxoid. Rates of pregnancy-/neonate-related AEs of interest, solicited general and unsolicited AEs were similar between groups. None of the serious AEs reported throughout the study were considered related to maternal Tdap vaccination. CONCLUSIONS: Tdap vaccination during pregnancy resulted in high levels of pertussis antibodies in cord blood, was well tolerated and had an acceptable safety profile. This supports the recommendation of Tdap vaccination during pregnancy to prevent early-infant pertussis disease. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02377349.