Dry eye disease (DED) is one of the most commonly encountered conditions for eye care practitioners. The prevalence of DED can be as high as 30% of the population. In the past decade, only one drug has been approved for the treatment of DED by the US Food and Drug Administration (FDA) in the USA (ie, Restasis ® by Allergan, Inc.). The total annual cost (ie, treatment and lost productivity due to symptoms) to the US economy of dry eye can be more than $55 billion. Thus, the development of new drug treatments for dry eye is important for both the dry eye patient and the ophthalmic industry. There are many drugs in development for the treatment of dry eye. This manuscript reviews the drugs listed on the ClinicalTrials.gov website (FDA list of clinical trials) being investigated for the treatment of dry eye. A large number of these drugs are designed to target a specific cause of dry eye and some of these drugs will be approved for clinical use in the next 10 years. This will result in a significant increase in the clinician's choice of treatment and potentially better control of the dry eye patient's condition.
Knowledge of eye position in the brain is critical for localization of objects in space. To investigate the accuracy and precision of eye position feedback in an unreferenced environment, subjects with normal ocular alignment attempted to localize briefly presented targets during monocular and dichoptic viewing. In the task, subjects’ used a computer mouse to position a response disk at the remembered location of the target. Under dichoptic viewing (with red (right eye)–green (left eye) glasses), target and response disks were presented to the same or alternate eyes, leading to four conditions [green target–green response cue (LL), green–red (LR), red–green (RL), and red–red (RR)]. Time interval between target and response disks was varied and localization errors were the difference between the estimated and real positions of the target disk. Overall, the precision of spatial localization (variance across trials) became progressively worse with time. Under dichoptic viewing, localization errors were significantly greater for alternate-eye trials as compared to same-eye trials and were correlated to the average phoria of each subject. Our data suggests that during binocular dissociation, spatial localization may be achieved by combining a reliable versional efference copy signal with a proprioceptive signal that is unreliable perhaps because it is from the wrong eye or is too noisy.
PURPOSE. To investigate the longitudinal change in horizontal and vertical ocular alignment in normal and prism-reared infant monkeys during the critical developmental period. METHODS. Ocular alignment was measured using Hirschberg photographic methods in 6 infant monkeys reared under prism-viewing from day 1 after birth to 4 months, and 2 monkeys reared with normal visual experience. Photographs were acquired twice a week for the first 6 months of life and analyzed to identify pupil center and the first Purkinje image from which eye positions and strabismus angle were calculated. RESULTS. At 3 weeks after birth, prism monkeys presented with significant horizontal ocular misalignment. A gradual change in alignment was seen in all prism-reared monkeys stabilizing at approximately 11 weeks, at which time 5 monkeys were exotropic (mean, 16°XT; range, 13°-24°) and 1 monkey was esotropic (5°ET). A reduction in ocular misalignment was observed after exposure to normal visual environment at 16 weeks, but at 34 weeks of age, that is, 18 weeks after removal of prisms, prism-reared monkeys displayed a mean horizontal strabismus of 7°XT (range, 2°ET to 20°XT), which was still significantly different from normal monkeys. CONCLUSIONS. Prism-rearing disrupts binocular fusion mechanisms, and horizontal and vertical strabismus is seen to develop as early as 3 weeks of age in monkey models, equivalent to approximately 3 months in humans. The time course of change in alignment overlaps with disruption in various visual sensory functions, suggesting a causal temporal link between sensory and motor mechanisms for alignment.
Contrast sensitivity functions reveal information about a subject’s overall visual ability and have been investigated in several species of nonhuman primates (NHPs) with experimentally induced amblyopia and glaucoma. However, there are no published studies comparing contrast sensitivity functions across these species of normal NHPs. The purpose of this investigation was to compare contrast sensitivity across these primates to determine whether they are similar. Ten normal humans and eight normal NHPs (Macaca fascicularis) took part in this project. Previously published data from Macaca mulatta and Macaca nemestrina were also compared. Threshold was operationally defined as two misses in a row for a descending method of limits. A similar paradigm was used for the humans except that the descending method of limits was combined with a spatial, two-alternative forced choice (2-AFC) technique. The contrast sensitivity functions were fit with a double exponential function. The averaged peak contrast sensitivity, peak spatial frequency, acuity, and area under the curve for the humans were 268.9, 3.40 cpd, 27.3 cpd, and 2345.4 and for the Macaca fascicularis were 99.2, 3.93 cpd, 26.1 cpd, and 980.9. A two-sample t-test indicated that the peak contrast sensitivities (P = 0.001) and areas under the curve (P = 0.010) were significantly different. The peak spatial frequencies (P = 0.150) and the extrapolated visual acuities (P = 0.763) were not different. The contrast sensitivities for the Macaca fascicularis, Macaca mulatta, and Macaca nemestrina were qualitatively and quantitatively similar. The contrast sensitivity functions for the NHPs had lower peak contrast sensitivities and areas under the curve than the humans. Even though different methods have been used to measure contrast sensitivity in different species of NHP, the functions are similar. The contrast sensitivity differences and similarities between humans and NHPs need to be considered when using NHPs to study human disease.
Knowledge of eye position in the brain is critical for localization of objects in space. To investigate the accuracy and precision of eye position feedback in an unreferenced environment, subjects with normal ocular alignment attempted to localize briefly presented targets during monocular and dichoptic viewing. In the task, subjects’ used a computer mouse to position a response disk at the remembered location of the target. Under dichoptic viewing (with red (right eye) - green (left eye) glasses), target and response disks were presented to the same or alternate eyes, leading to four conditions [green target – green response cue (LL), green-red (LR), red-green (RL), and red-red (RR)]. Time interval between target and response disks was varied and localization errors were the difference between the estimated and real positions of the target disk. Overall, the precision of spatial localization (variance across trials) became progressively worse with time. Under dichoptic viewing, localization errors were significantly greater for alternate-eye trials as compared to same-eye trials and were correlated to the average phoria of each subject. We suggest that during these tasks, subjects are unable to compensate for their phoria, implying that oculomotor proprioception may not provide the required feedback of eye position.
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