A Role for Thalamic Projection GABAergic Neurons in Circadian Responses to Light

The thalamus is an important hub for sensory information and participates in sensory perception, regulation of attention, arousal and sleep. These functions are executed primarily by glutamatergic thalamocortical neurons that extend axons to the cortex and initiate cortico-thalamocortical connectional loops. However, the thalamus also contains projection GABAergic neurons that do not extend axons toward the cortex. Here, we have harnessed recent insight into the development of the intergeniculate leaflet (IGL) and the ventral lateral geniculate nucleus (LGv) to specifically target and manipulate thalamic projection GABAergic neurons in female and male mice. Our results show that thalamic GABAergic neurons of the IGL and LGv receive retinal input from diverse classes of retinal ganglion cells (RGCs) but not from the M1 intrinsically photosensitive retinal ganglion cell (ipRGC) type. We describe the synergistic role of the photoreceptor melanopsin and the thalamic neurons of the IGL/LGv in circadian entrainment to dim light. We identify a requirement for the thalamic IGL/LGv neurons in the rapid changes in vigilance states associated with circadian light transitions.SIGNIFICANCE STATEMENT The intergeniculate leaflet (IGL) and ventral lateral geniculate nucleus (LGv) are part of the extended circadian system and mediate some nonimage-forming visual functions. Here, we show that each of these structures has a thalamic (dorsal) as well as prethalamic (ventral) developmental origin. We map the retinal input to thalamus-derived cells in the IGL/LGv complex and discover that while RGC input is dominant, this is not likely to originate from M1ipRGCs. We implicate thalamic cells in the IGL/LGv in vigilance state transitions at circadian light changes and in overt behavioral entrainment to dim light, the latter exacerbated by concomitant loss of melanopsin expression.     

Interpreting the Tinnitus Questionnaire (German version): what individual differences are clinically important?

Objective: Reporting of clinical significance is recommended because findings can be statistically significant without being relevant to patients. For aiding clinical interpretation of the Tinnitus Questionnaire (TQ), many investigators use a 5-point change cut-off as a minimal clinically important difference (MCID). But there are shortcomings in how this value was originally determined. Design: The MCID was evaluated by analysing retrospective clinical data on the TQ (German version). Following recommended standards, multiple estimates were computed using anchor- and distribution-based statistical methods. These took into account not only patients’ experience of clinical improvement, but also measurement reliability. Study sample: Pre- and post-intervention scores were assessed for 202 patients. Results: Our six estimates ranged from 5 to 21 points in TQ change score from pre- to post- intervention. The 5-point TQ change score was obtained using a method that considered change between groups, and did not account for measurement error or bias. The size of the measurement error was considerable, and this comprises interpretation of individual patient change scores. Conclusions: To enhance confidence that a TQ change over time in individual patients is clinically meaningful, we advise at least the median MCID of 12 points.     

Disposable contact lenses in penetrating keratoplasty.

PURPOSE: To evaluate the therapeutic efficacy of disposable contact lenses in management of complications after keratoplasty. METHODS: Twenty-eight patients with various post keratoplasty complications were fit with disposable contact lenses (45% Vifilcon A and 55% water content). Indications for lens use included persistent epithelial defects, wound leak, graft edema, dry eye and protection of normal corneal epithelium. RESULTS: Success was obtained with the therapeutic use of disposable lenses in 20 of the 28 cases. The best results were seen in maintenance and restoration of healthy ocular surface and small wound leaks. Stromal graft edema with no epithelial involvement was the major area of therapeutic failure. CONCLUSIONS: Disposable contact lenses are an attractive low cost option in the management of complications after keratoplasty. They are particularly useful in maintaining a healthy ocular surface, providing symptomatic relief and avoiding resurgery in patients with small wound leaks.