Kheirkhah A, Syed ZA, Satitpitakul V, Goyal S, Müller R, Tu EY, Dana R.
Sensitivity and Specificity of Laser-Scanning In Vivo Confocal Microscopy for Filamentous Fungal Keratitis: Role of Observer Experience. Am J Ophthalmol 2017;179:81-89.
AbstractPURPOSE: To determine sensitivity and specificity of laser-scanning in vivo confocal microscopy (LS-IVCM) for detection of filamentous fungi in patients with microbial keratitis and to evaluate the effect of observer's imaging experience on these parameters. DESIGN: Retrospective reliability study. METHODS: This study included 21 patients with filamentous fungal keratitis and 24 patients with bacterial keratitis (as controls). The etiology of infection was confirmed based on the response to specific therapy regardless of culture results. All patients had undergone full-thickness corneal imaging by a LS-IVCM (Heidelberg Retina Tomograph 3 with Rostock Cornea Module; Heidelberg Engineering, Heidelberg, Germany). The images were evaluated for the presence of fungal filaments by 2 experienced observers and 2 inexperienced observers. All observers were masked to the clinical and microbiologic data. RESULTS: The mean number of images obtained per eye was 917 ± 353. The average sensitivity of LS-IVCM for detecting fungal filaments was 71.4% ± 0% for the experienced observers and 42.9% ± 6.7% for the inexperienced observers. The average specificity was 89.6% ± 3.0% and 87.5% ± 17.7% for these 2 groups of observers, respectively. Although there was a good agreement between the 2 experienced observers (κ = 0.77), the inexperienced observers showed only a moderate interobserver agreement (κ = 0.51). The LS-IVCM sensitivity was higher in patients with fungal infections who had positive culture or longer duration of the disease. CONCLUSIONS: Although LS-IVCM has a high specificity for diagnosing filamentous fungal keratitis, its sensitivity is moderate and highly dependent on the level of the observer's experience and training with this imaging modality.
Kheirkhah A, Di Zazzo A, Satitpitakul V, Fernandez M, Magilavy D, Dana R.
A Pilot Randomized Trial on Safety and Efficacy of a Novel Topical Combined Inhibitor of Janus Kinase 1/3 and Spleen Tyrosine Kinase for GVHD-Associated Ocular Surface Disease. Cornea 2017;36(7):799-804.
AbstractPURPOSE: Janus kinase (JAK) and spleen tyrosine kinase (SYK) play critical functions in T-cell activation and in inflammation. Because of their antiinflammatory effects, JAK and SYK inhibitors have recently been evaluated in several immunopathogenic disorders. This pilot study was designed to assess the safety and efficacy of a topical combined JAK/SYK inhibitor, R348, ophthalmic solution for treatment of ocular surface disease in graft-versus-host disease (GVHD). METHODS: This phase 2, double-masked, randomized, pilot trial included 30 patients with ocular surface disease due to GVHD who were randomized to receive topical 0.5% R348, 0.2% R348, or vehicle, twice daily for 12 weeks. Before and after treatment, a comprehensive ophthalmic evaluation was performed, which included Ocular Surface Disease Index (OSDI) questionnaire, Ocular Comfort Index questionnaire, corneal fluorescein staining, conjunctival lissamine green staining, and Schirmer test with anesthesia. Changes in these parameters were compared between the 3 groups. RESULTS: The mean decrease in total corneal fluorescein staining at 12 weeks after treatment was higher in the 0.5% R348 group (-6.0 ± 3.9, NEI scoring) compared with the vehicle (-2.1 ± 2.6, P = 0.045) or the 0.2% R348 group (-4.1 ± 3.6, P = 0.34). However, there were no significant differences among the groups in terms of treatment-induced changes in OSDI, Ocular Comfort Index, conjunctival lissamine green staining, or Schirmer scores. R348 eye drops were well tolerated. CONCLUSIONS: This pilot study indicates that 0.5% R348 JAK/SYK inhibitor ophthalmic solution is well tolerated and may have some therapeutic efficacy in treating ocular GVHD. Larger trials are required to derive more definitive data.