Visual Psychophysics and Physiological Optics Effect of Age and Glaucoma on the Detection of Darks and Lights

PURPOSE. We have shown previously that normal observers detect dark targets faster and more accurately than light targets, when presented in noisy backgrounds. We investigated how these differences in detection time and accuracy are affected by age and ganglion cell pathology associated with glaucoma. METHODS. We asked 21 glaucoma patients, 21 age-similar controls, and 5 young control observers to report as fast as possible the number of 1 to 3 light or dark targets. The targets were positioned at random in a binary noise background, within the central 308 of the visual field. RESULTS. We replicate previous findings that darks are detected faster and more accurately than lights. We extend these findings by demonstrating that differences in detection of darks and lights are found reliably across different ages and in observers with glaucoma. We show that differences in detection time increase at a rate of approximately 55 msec/dB at early stages of glaucoma and then remain constant at later stages at approximately 800 msec. In normal subjects, differences in detection time increase with age at a rate of approximately 8 msec/y. We also demonstrate that the accuracy to detect lights and darks is significantly correlated with the severity of glaucoma and that the mean detection time is significantly longer for subjects with glaucoma than age-similar controls. CONCLUSIONS. We conclude that differences in detection of darks and lights can be demonstrated over a wide range of ages, and asymmetries in dark/light detection increase with age and early stages of glaucoma. Keywords: retina, thalamo-cortical, light-dark, perimetry, psychophysics V isual information travels from the eye to the rest of the brain through two major pathways that signal light increments (ON) and decrements (OFF) in local regions of visual space. In mammals, ON and OFF channels remain segregated in the thalamus and combine for the first time in visual cortex. However, ON-OFF cortical mixing is incomplete and unbalanced. Although single cortical neurons receive input from both channels, ON and OFF thalamic afferents segregate in different cortical domains 1-4 and cortical current sinks generated by OFF thalamic afferents are stronger and occupy larger territory than those generated by ON afferents. Moreover, cortical responses to dark stimuli are stronger, faster, more linearly related to luminance contrast, and have better spatial and temporal resolution than responses to light stimuli. 27-30 To investigate if dark/light asymmetries are affected by glaucoma within the central 308 of fixation, we asked human observers to report the number of dark or light targets presented in binary noise on a monitor screen. Our results demonstrated that darks are detected more accurately and faster than lights in control observers and observers with glaucoma. Moreover, we showed that these dark/light asymmetries increase with age and in the early stages of glaucoma. METHODS We recruited 21 patients with open angle glaucoma (48-83 years old; mean, 64.7 6 7.5 years old), 21 control observers with a similar age range (49-74 years old; mean, 62.2 6 7.3 years old), and 5 young control observers (21-25 years old). The study was performed following the principles outlined in the Declaration of Helsinki. The inclusion criteria for all groups were: best corrected visual acuity of at least 0.2 logMAR units (approximately 20/30), spherical equivalent refractive error within À6 to þ2 diopters (D), cylinder correction within 3 D, clear ocular media, and absence o

A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease

BACKGROUNDCreatine and minocycline were prioritized for testing in Phase II clinical trials based on a systematic evaluation of potentially disease modifying compounds for Parkinson disease (PD).OBJECTIVETo test whether creatine and minocycline alter the course of early PD relative to a predetermined futility threshold for progression of PD in a randomized, double-blind, Phase II futility clinical trial. Agents that do not perform better than the futility threshold are rejected as futile and are not considered for further study.METHODSParticipants had a diagnosis of PD within 5 years, but did not require medications for the management of symptoms. The primary outcome was the change in the total Unified Parkinson's Disease Rating Scale (UPDRS) score from baseline to either the time when there was sufficient disability to warrant symptomatic therapy for PD or 12 months, whichever came first. Subjects were randomized 1:1:1 to receive creatine 10 g/day, minocycline 200 mg/day, or matching placebo. The futility threshold was set as a 30% reduction in UPDRS progression based on the placebo/tocopherol arm of the Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism (DATATOP) trial. p values < or = 0.1 indicate futility.RESULTSTwo hundred subjects were randomized to the three groups. Neither creatine (p = 0.96) nor minocycline (p = 0.66) could be rejected as futile based on the DATATOP futility threshold. The rate of progression for the calibration placebo group fell outside the 95% CI for the DATATOP historical control. In a sensitivity analysis, based on the threshold derived from the calibration placebo group, again neither drug could be rejected as futile. Tolerability was 91% in the creatine group and 77% in the minocycline group. Common adverse events included upper respiratory symptoms (26%), joint pain (19%), and nausea (17%).CONCLUSIONSBoth creatine and minocycline should be considered for definitive Phase III trials to determine if they alter the long term progression of Parkinson disease (PD). Additional factors must be weighed before selecting agents for Phase III trials, including safety, tolerability, activity, cost, and availability of these two agents in comparison with other agents currently in development for PD

A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease

OBJECTIVETo determine if future studies of coenzyme Q(10) and GPI-1485 in Parkinson disease (PD) may be warranted.METHODSWe conducted a randomized, double-blind, calibrated futility clinical trial of coenzyme Q10 and GPI-1485 in early untreated PD using placebo data from the DATATOP study to establish the futility threshold.RESULTSThe primary outcome measure (change in total Unified Parkinson's Disease Rating Scale scores over 1 year) did not meet the prespecified criteria for futility for either agent. Secondary analyses using calibration controls and other more recent placebo data question the appropriateness of the predetermined definition of futility, and suggest that a more restrictive threshold may be needed.CONCLUSIONSCoenzyme Q(10) and GPI-1485 may warrant further study in Parkinson disease, although the data are inconsistent. Additional factors (cost, availability of other agents, more recent data on placebo outcomes, other ongoing trials) should also be considered in the selection of agents for Phase III studies