Safety and Efficacy of AGN-241622 for Presbyopia: Results From a First-in-Human, Phase 1/2, Randomized, Vehicle-Controlled Study.

IntroductionThe aim of this case series was to examine the association between unaided binocular visual acuity for near vision and pupil change after the instillation of a special topical formulation for presbyopia treatment.MethodsThis was a case series consisting of consecutive participants with presbyopia aged 40–70 years who were tested for visual acuity and pupil diameter before and 2 h after instillation of a formulation of pilocarpine and phenylephrine drops (FOV Tears) for presbyopia. Participants underwent subjective refraction, photopic and scotopic pupil diameter measurement and unaided monocular and binocular visual acuity testing by logMAR for distance and near vision both pre- and post-instillation of eye drops.ResultsThe study enrolled 363 subjects (n = 176 women, 48%) with a mean (± standard deviation) age of 50.4 ± 5.8 years. Mean spherical equivalent (SE) changed significantly (− 0.17 Diopters) after instillation of the FOV Tears formulation (p < 0.001). Post-instillation of eye drops, the scotopic pupil diameter decreased by 0.97 ± 0.98 mm, and the near visual acuity by logMAR improved significantly by nearly two lines (p < 0.01). In the linear regression analyses, age (p < 0.001) and SE pre-drop instillation (p < 0.001) were associated with unaided binocular visual acuity. The changes in photopic pupil diameter and the scotopic pupil diameter were not associated with unaided binocular visual acuity.ConclusionsThe use of the pilocarpine and phenylephrine formulation (FOV Tears) improved binocular visual acuity for near vision in presbyopic patients, and the effect was independent of pupil change.

Efficacy and safety profile of ketorolac 0.5% ophthalmic solution in the prevention of surgically induced miosis during cataract surgery

Treatment of Bilateral Refractive Amblyopia in Children Three to Less Than 10 Years of Age

Treatment of Acute Visual Loss in Giant Cell Arteritis

To assess the grating visual acuity of Chinese normal infants from 5 to 24 months, evaluate the development of grating visual acuity in infants. The Teller acuity card(TM) II (Stero-Optical Company, America) was used to assess the grating visual acuity of 244 infants aged from 5 to 24 months, who met the eligible criteria. Binocular visual acuity and monocular visual acuity were both assessed. They were divided into 19 groups according to their age sequence from 5 to 24 months. Average binocular and monocular visual acuity of every group were recorded and calculated. The relationship between visual acuity and age were analyzed. The practicality and possibility of the application for the Teller acuity card in infants were assessed. Binocular visual acuity was obtained in 241 infants (98.77%). Monocular visual acuity from both eyes was completed in 89.2% infants. All the tests can be finished in 2 to 5 minutes. The average of binocular visual acuities of the 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 21, 24 months separately was: 0.17, 0.21, 0.22, 0.23, 0.23, 0.25, 0.26, 0.30, 0.33, 0.32, 0.37, 0.39, 0.42, 0.47, 0.56, 0.60, 0.83. The average of monocular visual acuities separately was: 0.15, 0.19, 0.19, 0.20, 0.20, 0.21, 0.21, 0.27, 0.23, 0.26, 0.24, 0.35, 0.26, 0.41, 0.40, 0.56, 0.80. The binocular visual acuity was slightly higher than the monocular visual acuity. The difference was less than one octave. The intraocular acuity difference was less than one octave. There were no significant differences between left and right eyes. Visual acuity of the infants aged form 5 to 14 months increased slowly from 5.1 to 9.6cpd, about 1 octave. There was an increase started from 15 months. Everyone who was reached 24 months got a visual acuity of 26cpd (snellen = 0.833), closed to the adult level. Compared to the visual acuity of 12 months age, 1.5 octaves were increased. TAC is useful and practical for age norms of visual acuity of infants in clinical and vision research. Visual acuity increases progressively with age. The development of visual acuity shows a different speed in different age period. Monocular visual acuity is slightly lower than binocular visual acuity. There is a balanced visual development of both eyes.

All-Distance Visual Acuity and Contrast Visual Acuity in Eyes with a Refractive Multifocal Intraocular Lens with Minimal Added Power

Background/Aim. In aviation, visual functions are important for the simultaneous monitoring the instrument panel and signs in the environment. From the very beginning of the development of aviation, visual function has been deemed particularly important. The effect of +Gz acceleration on the organ of vision is very significant for investigations in aviation medicine. Visual functions are the most important of all sensory functions where flight safety and quality of flight performance are concerned. High acceleration onset rates may cause changes in pupil diameter of a pilot with significant changes in visual function. However, it is important to maintain visual functions due to rapid pilot?s orientation in the space. The aim of this study was to establish whether there was any pupillary response in Air Force and Air Defence pilots or changes in pupil diameter when exposed to +Gz acceleration in the human centrifuge. ??thods. The study was conducted on 65 Air Force and Air Defence pilots aged from 28 to 45 years of age. The pilots were exposed to an acceleration of +5.5Gz to +7Gz. We examined the obtained differences in pupil diameter according to a rate of acceleration in the period of three consecutive days. R?sults. Changes in pupil diameter during the pilot?s exposure to different high values of acceleration in the course of three days, measured before, during and after the exposure, generated statistically significant results. No statistically significant differences in pupil diameter were noticed when the pilots were exposed to the same values of acceleration before the testing on the first, second or third day. During the test, pupil diameter was statistically significantly larger than before the test. Conclusion. Transient changes in pupil diameter occurred in pilots exposed to a +7Gz acceleration. Pilots were able to withstand exposure to a +5.5Gz acceleration, without any major changes in the pupil diameter. Physiological training of pilots in the human centrifuge mimicking conditions of real G acceleration, improves tolerance to acceleration, which is important for flight safety.

Background: Estimation of time interval since death is an important aspect of forensic medicine, it is used as an evidence in both civil and criminal cases. There are multiple techniques used worldwide but reaction of pupil to chemical agents is currently the topic of interest. Studies on the role of pilocarpine in estimating the post-mortem interval (PMI) are very limited worldwide so the current study aimed to estimate the time interval since death using pilocarpine eye drops. Methods: An experimental Cross-sectional study was conducted at the department of forensic medicine and toxicology of a tertiary care hospital of Karachi (Autopsy Lab). The diameter of the pupil of each eye was measured using a Vernier caliper. After that 2% pilocarpine eye drops were administered to both eyes. About 10 to 15 minutes was allowed for pupillary reaction. The pupillary diameter was measured again after 25 minutes. The data was analyzed using Statistical Package for Social Science (SPSS) for Windows Version 22. p-value ≤ 0.05 was considered as significant. Results: The mean age of the study participants was 61 ± 13.4 years and reported significant association with the postmortem interval. The mean postmortem interval was 5 hours 42 minutes ± 3 hours 19 minutes. It has been noted that the longest duration of pupillary reaction was 16 hours 2 minutes. There was a strong correlation of postmortem interval with the change in pupillary diameter after pilocarpine drops. Soon after death, in initial 2 hours the change in pupillary diameter after pilocarpine was 98.8% while the percentage of pupillary reaction decreases as long as the time since death. After 16 hours of death there was no change in pupillary diameter after administering pilocarpine drops. Conclusion: It can be concluded that pupillary reaction after pilocarpine eye drops is significantly associated with time interval since death as 98.8% response was recorded in first two hours after death. The longest postmortem interval up to which the pupil can response to eye drop is 16 hours. Keywords: Pilocarpine, Postmortem interval, Pupillary reaction

Luminance-independent changes in pupil diameter (PD) during wakefulness influence and are influenced by neuromodulatory, neuronal, and behavioral responses. However, it is unclear whether changes in neuromodulatory activity in a specific brain area are necessary for the associated changes in PD or whether some different mechanisms cause parallel fluctuations in both PD and neuromodulation. To answer this question, we simultaneously recorded PD and cortical neuronal activity in male and female mice. Namely, we measured PD and neuronal activity during adaptation to sound contrast, which is a well-described adaptation conserved in many species and brain areas. In the primary auditory cortex (A1), increases in the variability of sound level (contrast) induce a decrease in the slope of the neuronal input-output relationship, neuronal gain, which depends on cortical neuromodulatory zinc signaling. We found a previously unknown modulation of PD by changes in background sensory context: high stimulus contrast sounds evoke larger increases in evoked PD compared with low-contrast sounds. To explore whether these changes in evoked PD are controlled by cortical neuromodulatory zinc signaling, we imaged single-cell neural activity in A1, manipulated zinc signaling in the cortex, and assessed PD in the same awake mouse. We found that cortical synaptic zinc signaling is necessary for increases in PD during high-contrast background sounds compared with low-contrast sounds. This finding advances our knowledge about how cortical neuromodulatory activity affects PD changes and thus advances our understanding of the brain states, circuits, and neuromodulatory mechanisms that can be inferred from pupil size fluctuations.

Objective To explore the clinical value of frosted glass eye-shade in monocular visual acuity measurement by comparison of binocular and monocular visual acuity under various cover condition in light. Methods A total of 247 people came for physical examination were made distance visual acuity measurement by three ways: one eye was covered by a fiosted glass plate, opaque eye-shade, and no cover as well respectively, then was compared with each other. Pupil diameter was also measured in the states, and it's relation to visual acuity was discussed. Results The monocular visual acuity under opaque eye-shade was lower then the other two. Comparing the monocular visual acuity under frosted glass eye-shade with binocular visual acuity, there was no remarkable meaning in the difference (q=2.05, P ＞0.05). Activity of pupil was in relation to the difference of visual acuity under various conditions. Conclusions Monocular visual acuity under frosted glass eye-shade is more real and steady, and is more close to binocular visual acuity. Key words: Monocular visual acuity; Binocular summation; Optometry; Monocular visual measurement under translucent cover; , Pupil diameter

Objective To study the relation of retinal nerve fiber layer thinning to clinical and physiologic measures of visual function in patients with MS or neuromyelitis optica and unilateral optic neuropathy. Methods We studied a cohort of control subjects (n = 64) and patients (n = 24) with evidence of unilateral thinning of their average retinal nerve fiber layer as measured by optical coherence tomography in order to characterize the relationship between ganglion cell axonal degeneration and its impact upon vision and pupillary light reflex metrics using infrared pupillometry. Results When compared to the normal fellow eye, and with respect to normal subjects’ eyes, we confirmed significant abnormalities in retinal nerve fiber layer thickness, total macular volume, low-contrast letter acuity, and pupillary reflex metrics in the eye with the thinner retinal nerve fiber layer. For each −5% change in pupil diameter, there was a corresponding 7.1 µm reduction in the average retinal nerve fiber layer thickness. There was a significant difference between the pupillary metric of percent change in diameter and a decrease in low-contrast letter acuity (P < 0.001). Each −5% change in pupil diameter was associated with a substantial 3.4 line loss of low-contrast letter acuity (P < 0.001). Each −5% change in pupil diameter was associated with a 0.2 mm2 decrease in total macular volume (P < 0.001). Conclusion These findings further corroborate the hypothesis that the retina can be utilized as a model to advance our understanding of the mechanisms of axonal and neurodegeneration, and the corresponding impact of these processes upon the pathophysiology of MS and related disorders.

To determine the effect of individual Zernike wavefront aberrations on binocular summation and binocular visual acuity. A 0.25-microm wavefront aberration of second, third and fourth order Zernike modes were introduced into a set of log minimum angle of resolution unit (logMAR) visual acuity charts convolved by CTView. Subjects were dilated and fitted with an artificial pupil of 3 mm. For each set of charts, right eye, left eye, and binocular acuity was measured. The gain in binocular visual acuity over monocular visual acuity was defined as binocular summation. The visual acuity lost binocularly reading aberrated charts was normalized for each subject and defined as the aberration induced loss in acuity. Binocular summation was 10.0% (95% limits of agreement 8.8 to 11.1%) in the unaberrated state and ranged from 17.3 to 3.4% in the Zernike modes studied. Binocular summation was greatest in defocus followed by coma and astigmatism. The aberration induced loss in monocular and binocular acuity was higher for Zernike modes with low angular frequency compared to those with high angular frequency. Linear regression showed a significant relationship between aberration-induced loss of visual acuity and binocular summation. A fixed amount of root mean square (RMS) aberration has a varied effect on binocular vision depending on the angular frequency and radial order of Zernike mode. Binocular vision has a positive effect in reducing the visual impact of aberrations as Zernike modes that suffer from the most loss of visual acuity also experience the greatest amounts of binocular summation.

Pupillometry has been used in the studies of postural control to assess cognitive load during dual tasks, but its response to increased balance task intensity has not been investigated. Furthermore, it is unknown whether side‐specific changes in pupil diameter occur with more demanding balance tasks providing additional insights into postural control. The two aims of this study were to analyze differences in steady‐state pupil diameter between balance tasks with increased intensity and to determine whether there are side‐specific changes. Forty‐eight healthy subjects performed parallel and left and right one‐legged stances on a force plate with and without foam with right and left pupil diameters measured with a mobile infrared eye‐tracker. Differences between balance tasks in parameters (average pupil diameter of each eye, average of both pupil diameters and the difference between the left and right pupil diameter) were analyzed using a two‐way repeated measures analysis of variance, and deep learning neural network models were used to investigate how pupillometry predicted each balance task. The pupil diameter of the left eye, the average pupil diameter of both eyes and the difference in pupil diameters increased statistically significantly from simpler to more demanding balance tasks, with this being more pronounced for the left eye. The deep learning neural network models revealed side‐specific changes in pupil diameter with more demanding balance tasks. This study confirms pupillary responses to increased intensity of balance task and indicates side‐specific pupil responses that could be related to task‐specific involvement of higher levels of postural control.

The pharmacological control of intraocular pressure (IOP) is as complex as any other physiological system. The influence of the parasympathetic side of the autonomic nervous system, acting through muscarinic cholinergic receptors, has long been known, and cholinergic agonists such as pilocarpine are widely used in treatment of glaucoma. The sympathetic nervous system influences IOP in a remarkable way; agonists and antagonists at alpha and beta adrenoceptors all lower IOP, probably by a variety of pharmacological actions which result in reduction of aqueous humour formation on one hand and decrease in outflow resistance on the other (Mishima, 1982; Mittag, 1983). Several drugs acting at adrenoceptors are used in management of glaucoma, including adrenaline, timolol (a beta-receptor antagonist) and guanethidine (which reduces noradrenaline release). The enzyme carbonic anhydrase is involved in aqueous humour formation, and inhibitors of the enzyme such as acetazolamide, and dichlorphenamide still have a place in treatment. There is considerable evidence that prostaglandins, particularly PGE2 and PGF22, can reduce IOP in several species (Bito et al., 1983), and it is probable that precipitation or aggravation of glaucoma by corticosteroids is due to their reduced production. If a stable prostaglandin analogue can be synthesized with topical activity in the eye, it might well prove of value in glaucoma. The influence ofdopamine receptor activity on IOP had not been recognized until recently, although it was known to be a neurotransmitter in the retina. A variety of dopamine receptor agonists, however, including bromocriptine, lergotrile and pergolide, have now been shown to produce doseand time-related ocular hypotension in rabbits and monkeys (Potter & Burke, 1982). Studies in normal volunteers showed that oral bromocriptine, 1.25 mg, produced a significant reduction in IOP at 3 and 4 hours after administration when compared with placebo under double-blind conditions (Mekki et al., 1983), the reduction being comparable in magnitude with that produced in healthy volunteers by oral or topical beta-adrenoceptor antagonists. A similar reduction in IOP was produced by 0.01% bromocriptine eye drops when compared with placebo in normal volunteers (Mekki et al., 1984). No change in systemic blood pressure, pupil diameter or plasma prolactin level accompanied these changes in IOP. Dopamine receptors are classified pharmacologically into DI and D2 receptors, bromocriptine being an agonist at D2 receptors. The role ofD2 receptors in the ocular hypotensive action was demonstrated in normal subjects by pretreating them with intravenous metoclopramide which completely abolished the fall in IOP produced by oral bromocriptine without influencing it when given alone (Mekki & Turner, 1985). Does bromocriptine lower IOP in ocular hypertension and glaucoma? The evidence of this is direct and indirect. Direct evidence has recently been provided by Wayyes et al. (1986) who studied 8 patients with chronic open-angle glaucoma, receiving treatment with pilocarpine or timolol eye drops. Bromocriptine in a single oral dose of 2.5 mg produced a significant reduction of more than 25% in IOP when compared with placebo. Indirect evidence was provided anecdotally by Lustig (1983) who reported that some patients with glaucoma who also had Parkinson's disease showed a fall in IOP when treatment was commenced with bromocriptine for their neurological disorder. He then proceeded to give bromocriptine 2.5 mg orally to patients with glaucoma but without Parkinson's disease, and found that it increased the fall in IOP produced by timolol in four offive patients. If these preliminary observations are confirmed in further prospective long-term trials, low dose topical or oral dopamine receptor agonists such as bromocriptine may be added to the list ofdrugs used in treatment of glaucoma. The mechanism of action is unclear. Some dopamine agonists are also partial agonists at alpha adrenoceptors, but the absence of change in pupil diameter suggests that alpha adrenoceptors are not primarily involved. Dynamic studies of aqueous flow in rabbits have indicated that the effect of bromocriptine is produced, at least in part, by suppression of aqueous humour formation (Potter et

This study proposes a convenient method of evaluating mental stress. The potential of monitoring changes in pupil diameter as a measure of human reliability while operating human-machine systems was examined experimentally. An experiment was carried out to clarify the relation between changes in pupil diameter and autonomic nervous activity by measuring an electrocardiogram and pupil diameter when 10 subjects completed a time-sensitive task. The electrocardiogram was measured using a multitelemeter system and pupil diameter was measured using an eye-mark recorder. Several relationships between changes in pupil diameter and autonomic nervous activity were revealed and indicated that measurement of pupil diameter was an effective indicator of autonomic nervous activity. Therefore, it may be possible to develop a monitoring system that measures changes in pupil diameter as an indicator of the mental state of workers operating human-machine systems.