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Biomedical subjects

N A McBrien

Publications and source records attributed to N A McBrien.

At least 37 records · Page 2Linked to original sources

Pirenzepine prevents form deprivation myopia in a dose dependent manner.

Previous studies have demonstrated that muscarinic antagonists, such as atropine and pirenzepine, block form deprivation myopia in avian and mammalian models. The aim of the present investigation was to establish dose-response curves for intravitreal and subconjunctivally injected pirenzepine and to determine receptor specificity. Chicks were monocularly deprived of form vision for five days and received daily injections of either pirenzepine or saline. Keratometry, retinoscopy and A-scan ultrasonography of axial ocular dimensions were then taken. Intravitreally injected pirenzepine was effective at preventing form deprivation myopia in a dose dependent manner with an ED50 of 175 micrograms. A 500 micrograms dose totally prevented induced myopia (+0.9 D versus -13.7 D) and axial enlargement (-0.14 mm versus +0.32 mm). Daily subconjunctival injection of pirenzepine was significantly less effective in preventing form deprivation myopia. Form deprivation myopia could still be induced in animals which had undergone pirenzepine treatment. Pirenzepine was effective in preventing the axial elongation associated with experimental myopia in a dose dependent manner and via a functional not toxic mechanism.

Animals↗

Form deprivation myopia: elastic properties of sclera.

Thinning of the posterior sclera may imply that stretching and/or weakening of the sclera plays a role in axial elongation of myopic eyes. We investigated the elastic stress-strain properties of sclera from developing tree shrew eyes made myopic by monocular deprivation (MD) of form vision. Five days of MD induced a relative myopia (mean +/- SEM) of -5.6 D +/- 0.6 D (retinoscopy) and a vitreous chamber elongation (deprived minus control) of 106 +/- 14 microns, n = 10 (ultrasonography). Posterior scleral test samples (2 mm wide) cut from myopic eyes were significantly thinner than their contralateral eye controls (149 +/- 4 microns versus 164 +/- 4 microns, n = 10, P < 0.01) when measured with a force-controlled micrometer. However, posterior sclera from control eyes was significantly thicker than that from age-matched normal eyes (164 +/- 4 microns versus 149 +/- 3 microns, n = 10, P < 0.01). Under uniaxial tension, posterior scleral samples from myopic eyes failed at 18% lower load (162 g versus 198 g) and extended approximately 25% more than controls at a load corresponding to 20 mm Hg intraocular pressure. These differences were largely accounted for by the differences in scleral thickness. Finite element modelling of tree shrew eyes using the material properties summarised above, implies that simple elastic stretching of the sclera accounts for less than 20% of the observed difference in axial length between myopic and contralateral control eyes.

Animals↗

Prevention of collagen crosslinking increases form-deprivation myopia in tree shrew.

To examine whether collagen crosslinking is important for the regulation of refractive development, tree shrews were treated with agents that block collagen crosslinking [beta-aminoproprionitrile (beta-APN), or D-penicillamine (DPA)] and underwent monocular deprivation (MD) of form vision by eyelid closure to induce myopia. MD began on the first day of visual exposure and continued for 75 days. After 15-20 days of visual exposure, daily intraperitoneal injections of beta-APN (beta-APN MD animals, n = 5) or DPA (DPA MD animals, n = 5) were administered for 17-21 days. beta-APN open animals (n = 5) received the same injection schedule, but both eyes remained open. Saline MD animals (n = 5) received i.p. saline and MD. At 75 days of visual exposure, the MD eyes of beta-APN treated tree shrews were highly myopic (-23.6 +/- 3.3 D) in comparison to their open control eyes. This was markedly greater than the difference in saline MD animals (-11.0 +/- 0.8 D). DPA MD animals showed a relative myopia of -14.3 +/- 2.2 D. The structural correlate of the myopia, elongation of the vitreous chamber in the deprived eyes relative to the control eyes, was significantly greater in the beta-APN MD animals 0.53 +/- 0.03 mm, which was not significantly different from the saline MD group. Thinning of the posterior sclera, but not the cornea, was observed in the deprived eyes of beta-APN treated tree shrews, along with a tessellated appearance to the fundus. The eyes of the beta-APN open animals showed no significant differences from normal. Beta-APN MD and DPA MD treated chickens did not develop greater myopia or vitreous chamber elongation than standard MD chickens. The selective effect of the lathyritic agents on the deprived eyes in tree shrew suggests that collagen crosslinking interacts, in the mammalian sclera, with a retinally-derived signal to regulate the elongation of the eye in myopia.

Aminopropionitrile↗

Experimental myopia in a diurnal mammal (Sciurus carolinensis) with no accommodative ability.

1. We examined the functional morphology of the intra-ocular muscles of the grey squirrel using pharmacological and histological methods. Using sympathomimetic (phenylephrine) and parasympathomimetic (carbachol) agents, administered by transcorneal iontophoresis, the response of the iris sphincter and dilator muscles and the ciliary muscle were recorded. Measurement techniques included both streak retinoscopy and coincidence optometry for measurement of ocular refraction and high resolution ultrasonography to monitor changes in the intra-ocular component dimensions. 2. The grey squirrel was found not to possess a functional accommodative system. No change in ocular refraction or intra-ocular dimensions could be induced with 40% carbachol. Marked changes in pupil diameter occurred with topical application of both phenylephrine (dilation) and carbachol (constriction). Histological findings were in agreement with pharmacological findings in showing well developed iris sphincter and dilator muscles but only a poorly developed ciliary muscle. 3. Calculation of the depth of focus of the grey squirrel eye reveals that this could be sufficient to account for the behavioural observations of near viewing habits. 4. We then determined whether we could induce axial elongation of the vitreous chamber and a consequent myopia by monocular deprivation (MD) of pattern vision. 5. Monocular deprivation of pattern vision produced a significant experimental myopia due to axial elongation of the vitreous chamber in the deprived eye. 6. The results demonstrate that a functional accommodative system is not necessary to induce experimental myopia in the grey squirrel eye.

Accommodation, Ocular↗

Atropine reduces experimental myopia and eye enlargement via a nonaccommodative mechanism.

PURPOSE: To determine whether the muscarinic antagonist atropine effectively reduces or prevents experimentally induced myopia via a nonaccommodative mechanism. METHODS: Chicks were monocularly deprived (MD) of pattern vision by placement of a translucent occluder over the left eye. In two of the three MD groups, chicks received a series of intravitreal injections of atropine (n = 8) or saline vehicle (n = 8) with MD. Control groups (n = 8) of chicks were employed to assess the effects of MD, intravitreal injections, and drug effects. RESULTS: In sham-injected or saline-injected MD chicks, 8 days of MD produced -18.5 D and -20.9 D of experimental myopia, respectively. In atropine-injected MD chicks, 8 days of MD produced only -2.8 D of experimental myopia. This significant reduction in experimentally induced myopia in atropine-injected MD chicks was associated with a marked reduction in the relative axial elongation of the deprived eye (0.21 mm) when compared to saline-injected or sham-injected MD chicks (1.04 mm and 1.00 mm). This reduction in axial length in atropine-injected MD chicks was predominantly the result of a reduction in vitreous chamber elongation, although a reduction in anterior segment depth also was observed. Mean equatorial diameter was significantly reduced in atropine-injected MD chicks compared to saline-injected and sham-injected MD chicks, although to a lesser extent. Control experiments demonstrated that intravitreally injected atropine did not reduce carbachol-induced accommodation or light-induced pupil constriction in the skeletal intraocular muscles of the chick eye. CONCLUSIONS: These findings demonstrate that chronic administration of the muscarinic antagonist atropine prevents experimentally induced myopia in chick via a nonaccommodative mechanism.

Accommodation, Ocular↗

Normal development of refractive state and ocular component dimensions in the tree shrew (Tupaia belangeri).

The normal development of refractive state, ocular components and simple visually-guided behaviors was examined in maternally-reared tree shrews. Six groups consisting of 5 animals each were anesthetized and examined after 0, 15, 30, 45, 60 and 75 days of normal binocular visual exposure. Measures in the 75-day group provided values for an improved schematic eye of the tree shrew. Cycloplegic refraction showed a marked hyperopia (+25 D) at eye opening which decreased rapidly during the first 15 days of visual exposure and stabilized near the value (+5 D) expected in an eye of this axial length (approx. 7.8 mm). Corneal radius increased slightly during development. Anterior segment depth, measured by A-scan ultrasonography, seemed to complete most of its development at an earlier age (15-30 days of visual exposure) than did other ocular parameters. Lens thickness increased steadily throughout development. Vitreous chamber depth increased rapidly until 15 days of visual exposure, and then decreased because the lens thickness increased more rapidly than axial length. Crude orienting to, and following of, large objects developed shortly after eye opening (median age at onset, 5 and 6 days, respectively). Triggered visual placing responses developed at about the same time that the refractive state completed the rapid drop from highly hyperopic values. The slowed rate of ocular development after 15 days of visual exposure may be related to increased retinal activity that is permitted by neural maturation and by the presence of a relatively well-focussed retinal image. The increased activity may influence the final dimensions of the eye to coordinate the axial length with the focal length of the eye.

Animals↗

The development of experimental myopia and ocular component dimensions in monocularly lid-sutured tree shrews (Tupaia belangeri)

Tree shrews were monocularly deprived (MD) from the day of eye opening for periods of 15, 30, 45, 60 and 75 days. The initial structural change after 15 days of MD was a flattening of the corneal curvature in the deprived eye causing a hyperopic increase in refraction, relative to the fellow control eye. A relative myopia was first observed after 30 days of deprivation and increased as the length of MD increased. Animals monocularly deprived for 75 days consistently showed high degrees of myopia (greater -10 D). An increase in vitreous chamber depth was found after 30 days of deprivation and continued to increase, relative to the control eye, throughout the developmental period under investigation. There was a strong correlation (r = 0.84) between increase in vitreous chamber depth and the amount of experimentally-induced myopia. Anterior chamber depth was shallower in the deprived eyes of all animals. The crystalline lens was also consistently thinner in the deprived eye. Based on optical modeling, the observed myopia was consistent with the changes in ocular component dimensions. The susceptible period for experimental myopia begins about 15 days after eye opening.

Animals↗

Prevalence of myopia and myopic progression in a population of clinical microscopists.

The frequency of refractive errors in a population of clinical microscopists is presented. The prevalence of myopia in this population (N = 251) was found to be 71%, with 49% of the population reporting onset or progression of myopia after entry into clinical microscopy (after 21 years of age). Of subjects undergoing renewed progression of an existing myopia since starting clinical microscopy, 56% reported no refractive change for the 5 years before entering their profession. Accuracy of reporting refractive changes was found to be high. No differences were found in task-related functions between those subjects reporting myopic change in adulthood from those who did not report myopic change.

Adult↗

Differences in adaptation of tonic accommodation with refractive state.

It has recently been demonstrated that intersubject variations in tonic (dark focus) levels of accommodation are related to corrected refractive state (McBrien and Millodot, 1987). The aim of the present study was to investigate the effect of sustained visual tasks on the tonic level of accommodation in different refractive groups. Eleven hyperopes, 16 emmetropes, ten early onset myopes and ten late onset myopes had their tonic accommodation measured with the objective infrared optometer Canon Autoref R-1 before and after a 15 min sustained visual counting task. The post-task tonic accommodation level was monitored for 15 min to assess the decay rate of any observed task-induced changes in tonic accommodation. Subjects repeated the experimental procedure for four task locations (6 m, pre-task tonic position, 37 cm and 20 cm). Late onset myopes showed significant positive (myopic) changes in their tonic level of accommodation at both near viewing distances, which showed no evidence of decay during the 15 min post-task monitoring period. Hyperopes, however, underwent transient "counteradaptive" decreases in their tonic level of accommodation after sustained near viewing. Emmetropes and early onset myopes showed little change in tonic levels at the two near distances. Differences between groups were also obtained at tonic and far viewing distances. Post-task changes in tonic accommodation demonstrated only a weak negative correlation with pre-task tonic accommodation levels at each task distance. It is proposed that the observed differences in adaptation of tonic accommodation among refractive groups may be related to variations in autonomic innervation of the ciliary muscle.

Accommodation, Ocular↗

A biometric investigation of late onset myopic eyes.

There is a paucity of biometric information on late onset myopia (onset after 15-years-old). The present investigation compared the ocular component dimensions of 30 late onset myopes and 30 emmetropes, who were both age and sex matched. Measurement techniques included A-scan ultrasonography and keratometry. The findings revealed that the ultimate cause of late onset myopia is vitreous chamber elongation. Late onset myopes were also found to have significantly deeper anterior chambers and thinner crystalline lenses, no differences being found in corneal curvature measures. Possible mechanisms leading to these observed biometric differences are discussed in the light of recent findings.

Adolescent↗

The relationship between tonic accommodation and refractive error.

It is now well established that accommodation adopts an intermediate resting position in the absence of visual stimulation. It also has been shown that this tonic position of accommodation exhibits considerable variation among individuals (ie, 0-4 D). Previous studies have been somewhat inconclusive as to whether these individual differences in tonic accommodation are related to the refractive properties of the eye. This study investigates the relationship between tonic accommodation and refractive error with particular reference to both the value and the time course of tonic accommodation. Sixty-two subjects were used for the study, with an age range of 19-25 yr. Subjects were placed into one of four refractive groups, after considering factors pertaining to the theories of refractive development. Darkroom measures of tonic accommodation were determined using the infrared objective autorefractor, Canon Autoref R-1. Significant differences were found among the four refractive groups, with corrected hyperopes having the highest dioptric value of tonic accommodation and corrected late-onset myopes having the lowest dioptric value. The significant difference found between early- and late-onset myopes is suggested as a possible reason for the inconclusive results of some previous studies. It also was found that the time taken to reach a stable tonic position of accommodation was much slower for the hyperopic group than for the other refractive groups. The results are discussed in the light of recent findings on accommodative hysteresis and with respect to a dual innervation to the ciliary muscle.

Accommodation, Ocular↗

Effect of fixation target on objective refraction.

The effect of changes of fixation target color and detail on objective refraction were assessed using the Canon Autoref R-1. In addition, the effect of ambient illumination on objective refractive results for various color fixation targets was studied. The results show that any differences induced in emmetropic observers by different color and fixation targets, at different light levels, are small.

Adolescent↗

Amplitude of accommodation and refractive error.

This paper investigates the amplitude of accommodation of early onset myopes, late onset myopes, emmetropes, and hyperopes. Eighty subjects were used, 41 women and 39 men, with an age range of 18-22 yr (mean = 19.82). All subjects wore an optimum refractive correction, giving visual acuities of 20/20 or better. Significant differences were found between the four refractive groups, with late onset myopes having the largest amplitude of accommodation, followed by early onset myopes, emmetropes, and hyperopes. The results are discussed in the light of previous findings on tonic accommodation and the accommodative response gradient and interpretated in the context of a dual innervation to the ciliary muscle.

Accommodation, Ocular↗

The effect of refractive error on the accommodative response gradient.

The accommodative responses of early-onset myopes, late-onset myopes, emmetropes and hyperopes were measured over a range of 5 dioptres using an objective infra-red autorefractor. Differences were found between the four refractive groups, with hyperopes accommodating more for near targets than emmetropes, followed by early-onset myopes then late-onset myopes. Moreover a strong correlation between the accommodative response gradient and refractive error was found, suggesting that hyperopes accommodate more to a particular target than do emmetropes or myopes. The results are interpreted in the context of a dual innervation to the ciliary muscle.

Accommodation, Ocular↗

Clinical evaluation of the Canon Autoref R-1.

A clinical evaluation of the Canon Autoref R-1 was carried out on 93 subjects (186 eyes). Results were compared to clinical refractive data. A measure of the R-1 reliability was obtained both for successive measurements and measurements repeated on separate occasions. The validity of the instrument was found to be similar to that found in other investigations.

Adolescent↗

A review and evaluation of theories of refractive error development.

A review of theories of the development of refractive errors is presented. These are classified into three major groups: the biological-statistical theories, the use-abuse theories and theories of emmetropization. They are commented upon and their merits contrasted. Current research developments which relate to these theories are discussed.

Adolescent↗

Lid-suture myopia in tree shrews with retinal ganglion cell blockade.

To determine whether central communication of retinal signals is necessary for the development of an experimentally induced myopia, tree shrews were exposed to monocular deprivation (MD) while the action potentials of retinal cells in the deprived eye were blocked with intravitreally injected tetrodotoxin (TTX-MD animals). TTX injections (0.6 microgram in 3 microL) and MD began about 15 days after eye opening, at the start of the susceptible period for the development of lid-suture myopia. Six injections were given, one every second day to produce 12 days of MD and TTX-blockade. Control TTX animals (TTX-open) received TTX in one eye, but not MD, on the same injection schedule and were always found to be behaviorally unresponsive to visual stimuli through the injected eye indicating that TTX blocked central communication of action potentials. Other control animals received intravitreally injected saline in either an open eye (saline-open), or an MD eye (saline-MD). A sham-injected group (sham-inj-MD) received MD and all anesthetic and surgical manipulations except for penetration of the sclera. In all groups, one eye in each animal was an untreated control. Two effects were found. All MD groups, including the TTX-MD animals, developed a significant vitreous chamber elongation in the deprived eye, indicating that an experimental myopia developed despite ganglion cell blockade. Thus, retinal mechanisms in tree shrew can detect the presence of a degraded visual image and produce an experimental myopia that does not depend on the receipt of visual messages by central neural structures. In addition, eyes in which the sclera was punctured had smaller vitreous chamber depths than comparable uninjected eyes, indicating that puncturing the sclera reduced the normal elongation. These data suggest that forces within the eye normally contribute to its expansion and may be resisted by the choroid and/or the sclera.

Action Potentials↗