The Ocular Conjunctiva as a Mucosal Immunization Route: A Profile of the Immune Response to the Model Antigen Tetanus Toxoid

Background: In a quest for a needle-free vaccine administration strategy, we evaluated the ocular conjunctiva as an alternative mucosal immunization route by profiling and comparing the local and systemic immune responses to the subcutaneous or conjunctival administration of tetanus toxoid (TTd), a model antigen. Materials and methods: BALB/c and C57BL/6 mice were immunized either subcutaneously with TTd alone or via the conjunctiva with TTd alone, TTd mixed with 2% glycerol or TTd with merthiolate-inactivated whole-cell B. pertussis (wBP) as adjuvants. Mice were immunized on days 0, 7 and 14 via both routes, and an evaluation of the local and systemic immune responses was performed two weeks after the last immunization. Four weeks after the last immunization, the mice were challenged with a lethal dose (2 x LD50) of tetanus toxin. Results: The conjunctival application of TTd in BALB/c mice induced TTd-specific secretory IgA production and skewed the TTd-specific immune response toward a Th1/Th17 profile, as determined by the stimulation of IFN gamma and IL-17A secretion and/or the concurrent pronounced reduction of IL-4 secretion, irrespective of the adjuvant. In conjunctivaly immunized C57BL/6 mice, only TTd administered with wBP promoted the establishment of a mixed Th1/Th17 TTd-specific immune response, whereas TTd alone or TTd in conjunction with glycerol initiated a dominant Th1 response against TTd. Immunization via the conjunctiva with TTd plus wBP adjuvant resulted in a 33% survival rate of challenged mice compared to a 0% survival rate in non-immunized animals (p lt 0.05). Conclusion: Conjunctival immunization with TTd alone or with various adjuvants induced TTd-specific local and systemic immune responses, predominantly of the Th1 type. The strongest immune responses developed in mice that received TTd together with wBP, which implies that this alternative route might tailor the immune response to fight intracellular bacteria or viruses more effectively

Management of high-risk corneal grafts

MACMILLAN BUILDING,4 CRINAN ST, LONDON, ENGLAND, N1 9X

Longitudinal changes in dry eye symptoms and signs following lifitegrast therapy and relationship to tear osmolarity

Jay S Pepose,1 Mujtaba A Qazi,2 Douglas K Devries3 1Pepose Vision Institute, Chesterfield, MO, USA; 2Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO, USA; 3Eye Care Associates of Nevada, Sparks, NV, USA Background: This study measured longitudinal changes in dry eye disease (DED) symptoms and signs following lifitegrast therapy and assessed their relationship to tear osmolarity to test the hypothesis that a decline in tear osmolarity is a reliable leading indicator of subsequent improvement in DED symptoms and signs after initiating lifitegrast treatment.Methods: This phase IV, prospective, single-arm, open-label, 12-week study enrolled subjects aged ≥18 years with eye dryness score ≥40 (0–100 VAS) and tear osmolarity ≥308 mOsm/L. Subjects were prescribed lifitegrast ophthalmic solution 5%, twice daily in each eye. DED symptoms were assessed via VAS at baseline and 2, 6, and 12 weeks. Signs included tear osmolarity, meibomian gland dysfunction, tear breakup time, and fluorescein corneal staining. In post-hoc analysis, subjects with ≥5 mOsm/L decrease in osmolarity over 12 weeks were Responders.Results: Of 26 subjects in the intent-to-treat population, 23 were female; mean age was 67.4 years. Baseline mean±SD eye dryness was 68.7±16.5 and tear osmolarity was 317.8±8.5 mOsm/L. All seven symptoms (dryness, burning, foreign body sensation, pain, photophobia, itching, blurred vision) declined significantly (P<0.01) from baseline to 6 and 12 weeks. Signs did not change significantly. For 13 Responders, tear osmolarity decreased from baseline to 12 weeks (319.2±8.5 to 300.6±12.3 mOsm/L, P<0.001) and corneal staining trended toward improvement (1.1±0.9 to 0.6±0.7, P=0.136). Among Nonresponders, osmolarity increased from 316.4+8.7 to 329.6+13.9 (P<0.01) and corneal staining showed no change (1.3±0.8 to 1.0±0.7 at 12 weeks, P=0.293).Conclusions: Lifitegrast reduced DED symptoms among subjects with moderate-to-severe disease (severity defined by VAS for eye dryness). Potential reasons that may underlie the dichotomous effect of drug treatment on tear osmolarity are discussed. Keywords: dry eye, ocular drug therapy, tear deficiency, lifitegras

A randomized controlled trial of povidone-iodine/dexamethasone ophthalmic suspension for acute viral conjunctivitis

Jay S Pepose,1,2 Abhijit Narvekar,3 Wenlei Liu,4 Reza Haque3 1Pepose Vision Institute, Chesterfield, MO, USA; 2Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO, USA; 3Ophthalmics, Shire, A Takeda Company, Lexington, MA, USA; 4Biostatistics and Programming, Shire, A Takeda Company, Lexington, MA, USA Purpose: To evaluate the clinical safety and efficacy of povidone-iodine (PVP-I) 0.6%/dexamethasone (DEX) 0.1% ophthalmic suspension vs vehicle in patients with clinically suspected acute viral conjunctivitis. Patients and methods: This was a randomized, double-masked, parallel-group, vehicle-controlled study. Adults with a clinical diagnosis of suspected acute viral conjunctivitis were randomized 1:1 to PVP-I/DEX ophthalmic suspension or vehicle bilaterally four times daily for 5 days (Days 1–5). Evaluation was on Days 1, 3 (+1-day window), and 6 (+1). Patients with signs of acute viral conjunctivitis at the Day 6 visit received open-label PVP-I/DEX for five additional days and were evaluated on Day 11–14. The primary efficacy endpoint was clinical resolution of acute viral conjunctivitis in the study eye at the Day 6 visit. Results: Overall, 132 patients were randomized and received treatment (PVP-I/DEX, n=66; vehicle, n=66); 38 patients continued into the open-label portion of the study. Not enough patients with confirmed adenoviral conjunctivitis (n=32/132) were enrolled to assess the primary endpoint, although there were some efficacy trends in the PVP-I/DEX group for global clinical score (sum of watery conjunctival discharge and bulbar conjunctival redness). There were no serious treatment-emergent adverse events (TEAEs) and no patients discontinued due to a TEAE. In the masked phase, 56.1% of patients receiving PVP-I/DEX experienced at least one TEAE vs 43.9% in the vehicle group; 78.9% of patients in the open-label phase experienced at least one TEAE. Most TEAEs were mild in severity. Conclusion: PVP-I/DEX ophthalmic suspension administered for ≤14 days had a favorable safety profile and was generally well tolerated. Keywords: adenoviral conjunctivitis, dexamethasone, povidone-iodine, randomized controlled tria