Comparative study of 3 techniques to detect a relative afferent pupillary defect.

PURPOSE: To compare the standard method of testing for a relative afferent pupillary defect (RAPD) using the Standard Swinging Flashlight Method (S-SFM) with 2 novel techniques, to evaluate the validity and reproducibility of each method, and to validate the clinical significance of detecting more subtle RAPDs by correlating the extent of glaucoma damage with the presence or absence of an RAPD as assessed by each method. PATIENTS AND METHODS: In this prospective, observational study 101 consecutive patients (68 diagnosed glaucoma patients, 20 glaucoma suspects including ocular hypertensives, and 13 controls) were screened for the presence or absence of an RAPD using the S-SFM, Magnifier-Assisted Swinging Flashlight Method (MA-SFM), and Ophthalmoscopic Swinging Flashlight Method . Humphrey visual field mean deviation (MD) of each eye and the intereye differences in MD and Disc damage likelihood score (DDLS) and intereye difference in DDLS were calculated. Sensitivities for each method (S-SFM, MA-SFM, and Ophthalmoscopic Swinging Flashlight Method) were calculated at increasing levels of change in DDLS and MD. Weighted κ scores were calculated for agreement between tests. RESULTS: MA-SFM is the most sensitive method for determining an RAPD in terms of both intereye difference in DDLS and intereye differences in MD at all levels of change. Weighted κ scores revealed substantial agreement between tests for the same method, and moderate to substantial agreement among the observers. CONCLUSIONS: This study confirms results of our earlier study suggesting that swinging flashlight test modified with magnification (MA-SFM) can provide a simple, inexpensive, reproducible method of detecting an RAPD.

Metallothionein I and II mitigate age-dependent secondary brain injury.

Both the immediate insult and delayed apoptosis contribute to functional deficits after brain injury. Secondary, delayed apoptotic death is more rapid in immature than in adult CNS neurons, suggesting the presence of age-dependent protective factors. To understand the molecular pathobiology of secondary injury in the context of brain development, we identified changes in expression of oxidative stress response genes during postnatal development and target deprivation-induced neurodegeneration. The antioxidants metallothionein I and II (MT I/II) were increased markedly in the thalamus of adult C57BL/6 mice compared to mice <15 days old. Target deprivation generates reactive oxygen species that mediate neuronal apoptosis in the central nervous system; thus the more rapid apoptosis observed in the immature brain might be due to lower levels of MT I/II. We tested this hypothesis by documenting neuronal loss after target-deprivation injury. MT I/II-deficient adult mice experienced greater thalamic neuron loss at 96 hr after cortical injury compared to that in controls (80 +/- 2% vs. 57 +/- 4%, P < 0.01), but not greater overall neuronal loss (84 +/- 4% vs. 79 +/- 3%, MT I/II-deficient vs. controls). Ten-day-old MT I/II-deficient mice, however, experienced both faster onset of secondary neuronal death (30 vs. 48 hr) and greater overall neuronal loss (88 +/- 2% vs. 69 +/- 4%, P = 0.02). MT I/II are thus inhibitors of age-dependent secondary brain injury, and the low levels of MT I/II in immature brains explains, in part, the enhanced susceptibility of the young brain to neuronal loss after injury. These findings have implications for the development of age-specific therapeutic strategies to enhance recovery after brain injury.