Triazole-derivatized near-infrared cyanine dyes enable local functional fluorescent imaging of ocular inflammation.

Near-infrared (NIR) chemical fluorophores are promising tools for in-vivo imaging in real time but often succumb to rapid photodegradation. Indocyanine green (ICG) is the only NIR dye with regulatory approval for ocular imaging in humans; however, ICG, when employed for applications such as labelling immune cells, has limited sensitivity and does not allow precise detection of specific inflammatory events, for example leukocyte recruitment during uveitic flare-ups. We investigated the potential use of photostable novel triazole NIR cyanine (TNC) dyes for detecting and characterising activated T-cell activity within the eye. Three TNC dyes were evaluated for ocular cytotoxicity in-vitro using a MTT assay and optimised concentrations for intraocular detection within ex-vivo porcine eyes after topical application or intracameral injections of the dyes. TNC labelled T-cell tracking experiments and mechanistic studies were also performed in-vitro. TNC-1 and TNC-2 dyes exhibited greater fluorescence intensity than ICG at 10 µM, whereas TNC-3 was only detectable at 100 µM within the porcine eye. TNC dyes did not demonstrate any ocular cell toxicity at working concentrations of 10 µM. CD4+T-cells labelled with TNC-1 or TNC-2 were detected within the porcine eye, with TNC-1 being brighter than TNC-2. Detection of TNC-1 and TNC-2 into CD4+T-cells was prevented by prior incubation with dynole 34-2 (50 µM), suggesting active uptake of these dyes via dynamin-dependent processes. The present study provides evidence that TNC dyes are suitable to detect activated CD4+T-cells within the eye with potential as a diagnostic marker for ocular inflammatory diseases.

Headache Diary Mobile Application for Monitoring and Characterizing Posttraumatic Headaches.

OBJECTIVE: This study analyzed the data collected using a headache diary mobile application to characterize posttraumatic headaches (PTHs) in a sample of US veterans. Specifically, we measured patient engagement with the mobile application and compared our findings with previous literature regarding PTHs. SETTING: A Headache Center of Excellence (HCoE) in a Veterans Health Administration facility. PARTICIPANTS: Forty-nine veterans currently being treated for ongoing PTH-related complaints with English fluency, reliable access to the internet, and a mobile phone. DESIGN: Observational study of PTH characteristics using the mobile application over the course of 1 year. MEASURES: Main outcome measures were collected via a headache diary mobile application developed for patients to track headache-associated symptoms, headache location, triggers, type, intensity, and duration. Patients also completed a baseline Headache Impact Test (HIT-6) survey. RESULTS: In total, 1569 entries were completed during the first year of application deployment. On average, patients completed 2.5 entries per week and used the application for 70 days. They frequently reported associated PTH symptoms of photophobia (56.7%) and headaches triggered by emotional stress (35.1%). Network analyses revealed patterns of co-occurrence in triggers of headache pain, associated symptoms, and headache pain location. Headache pain severity and impact ratings from the headache diary demonstrated convergent validity with the established HIT-6 measure. CONCLUSIONS: Headache diary mobile applications are a promising tool for monitoring and characterizing PTHs in veterans. Present results mirror past studies of PTH characteristics. Mobile application headache diaries may be used in both clinical and research settings to monitor headache symptoms and communicate the functional impact of headaches in real time.