A novel eye drop application monitor to assess patient compliance with a prescribed regimen: a pilot study.

PURPOSE: To assess the ability of a novel imaging device to allow physicians to personalize therapeutic regimens based on objective patient drop administration data. METHODS: A novel imaging system was used to record video of the drop technique of subjects in clinic (n=25) or at home (n=17) for 1 week. Video assessment by a reading center was compared with patient reporting and their prescribed regimen with respect to how many drops were applied and how many landed in the eye. RESULTS: Reading center assessment of both drops dispensed and drops landing in the eye was significantly different from the prescribed regimen in the clinic (Pd=0.005, Pi<0.001, respectively) and at-home arms (Pd=0.003, Pi<0.001, respectively). CONCLUSIONS: This imaging system is a powerful tool to help physicians tailor patient therapy more accurately, to help researchers evaluate new drop therapies with objective rather than subjective data, and to potentially facilitate better patient training for improved drug delivery.

gammadelta T cells as regulators of airway hyperresponsiveness.

Airway responsiveness (AR) is determined by complex mechanisms reflecting lung responses to airborne stimuli. Murine studies have identified a number of potential factors modulating AR and thus have contributed to the current understanding of these mechanisms. In allergic inflammation, immune cells, in particular alphabeta T cells, have emerged as important contributors to increased AR. We have found that in contrast to alphabeta T cells, gammadelta T cells can have a negative regulatory effect on AR. Here, we review the current studies on gammadelta T cells in allergic inflammation and discuss their role in modulating AR. We propose that gammadelta T cells exhibit different immune properties depending on the type of stimulus and inflammation. These differential immune properties appear to be associated with specific gammadelta T cell subsets, which control AR to airborne stimuli. In particular, our recent data indicate that the Vgamma4(+) T cell subset acts as an important negative regulator of AR and contributes to maintaining normal lung function in mice.

Irreversible corneal decompensation in patients treated with topical dorzolamide.

PURPOSE: To describe irreversible corneal decompensation after topical dorzolamide hydrochloride (Trusopt; Merck and Co, Inc, West Point, Pennsylvania) therapy in nine patients who had histories consistent with corneal endothelial compromise. METHOD: Multicenter review of patients' charts. RESULTS: Nine eyes of nine patients developed overt corneal decompensation after starting topical dorzolamide, a condition that did not resolve with drug cessation. This occurred after 3 to 20 weeks (mean, 7.8) of therapy. All nine patients had undergone intraocular surgery. Eight patients had undergone cataract surgery; three were aphakic and three had posterior chamber intraocular lenses. Two patients had anterior chamber intraocular lenses and also had undergone trabeculectomies. Four patients had undergone penetrating keratoplasties, each case complicated by episodes of corneal allograft rejection that were successfully treated. Two patients had asymptomatic Fuchs endothelial dystrophy. Seven patients have since undergone successful penetrating keratoplasties. CONCLUSION: The reports suggest that dorzolamide can cause irreversible corneal edema in a subset of glaucoma patients with endothelial compromise. The findings suggest a rationale for research into the long-term effects of dorzolamide on the corneal endothelium.

Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF.

Apoptosis in vivo is followed almost inevitably by rapid uptake into adjacent phagocytic cells, a critical process in tissue remodeling, regulation of the immune response, or resolution of inflammation. Phagocytosis of apoptotic cells by macrophages has been suggested to be a quiet process that does not lead to production of inflammatory mediators. Here we show that phagocytosis of apoptotic neutrophils (in contrast to immunoglobulin G-opsonized apoptotic cells) actively inhibited the production of interleukin (IL)-1beta, IL-8, IL-10, granulocyte macrophage colony-stimulating factor, and tumor necrosis factor-alpha, as well as leukotriene C4 and thromboxane B2, by human monocyte-derived macrophages. In contrast, production of transforming growth factor (TGF)-beta1, prostaglandin E2, and platelet-activating factor (PAF) was increased. The latter appeared to be involved in the inhibition of proinflammatory cytokine production because addition of exogenous TGF-beta1, prostaglandin E2, or PAF resulted in inhibition of lipopolysaccharide-stimulated cytokine production. Furthermore, anti-TGF-beta antibody, indomethacin, or PAF receptor antagonists restored cytokine production in lipopolysaccharide-stimulated macrophages that had phagocytosed apoptotic cells. These results suggest that binding and/or phagocytosis of apoptotic cells induces active antiinflammatory or suppressive properties in human macrophages. Therefore, it is likely that resolution of inflammation depends not only on the removal of apoptotic cells but on active suppression of inflammatory mediator production. Disorders in either could result in chronic inflammatory diseases.