[Ophthalmoneurology. IV. The pupillary reflex and its disorders. 3. Pharmacology of the pupil].
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In spite of the clarification of some significant physiological factors of visual fatigue caused by VDT work, pupillary reflexes have not been studied as to how they are affected after prolonged visual work. This study examined visual function changes objectively in terms of pupillary reflexes and lens accommodative responses after a 4-hr VDT operation task. The relationship between the two functions was also examined. Two measurements in this paper revealed the physiological function changes due to VDT operation. The subjects involved were five students with an average age of 22.6 years. First, near-reflex measurement ascertained decreases in amplitude and the velocity of accommodation function after the visual task. Second, light-reflex measurement revealed a delay of the reflex, an increase in the amplitude of the reflex, and a decrease in pupil size after the visual task. A weak correlation between the decrease in pupil size and accommodation function was found. The occurrence of visual fatigue due to 4-hr VDT operation was also confirmed by CFF measurements and reported subjective visual symptoms in this experiment.
Trigeminal stimulation can induce pupillary changes. In vivo and in vitro studies have demonstrated that electrical impulses applied at the trigeminal level can provoke a miotic response, whose nature has been ascribed to the anti-dromic release of neuropeptides (substance P in particular). In order to better define the pupil response to trigeminal stimulation, we investigated the human pupil response to quantified (painless and painful) corneal stimuli by means of a combined (neurophysiological and pharmacological) technique. The response to corneal stimulation was bilateral, direct and consensual. It had a biphasic progression with an initial mydriasis (which directly correlated with the stimulus intensity), followed by a miotic phase. The mydriatic phase disappeared after thymoxamine application, while homatropine pre-treatment prevented occurrence of the miotic phase. The data obtained indicate that the pupillary response to corneal stimulation (trigemino-pupillary reflex) is a multisynaptic reflex with an afferent branch involving the trigeminal system, and an afferent branch involving both the sympathetic and the parasympathetic system. Other pathways, such as the SP-mediated release of acetylcholine, cannot be excluded. Thus the reflex appears to be a potentially useful tool for investigating pain/vegetative interactions in various clinical conditions. In turn, the description of its changes in pathologies characterized by a sympathetic/parasympathetic deficit or by a SP-ergic imbalance will allow us to better describe its inner mechanisms.
The existence of a true neuronal consensual pupillary reflex (CPR) in birds has long been debated. In this century Noll (Noll, A. (1915). Archiv für Physiologie (Leipzig), 350-372.) claimed to observe a neuronal CPR in a pigeon, but this was contradicted by Levine (Levine, J. (1955). Science, 122, 699.), who observed a direct transillumination effect (Durchleuchtungs-effekt) due to the retinas of the two eyes of the pigeon being in close apposition. To determine if a neuronal CPR exists, we transected the optic nerves of 28 chicks and observed and videotaped the direct and indirect pupillary responses. Twenty-one of the chicks exhibited no direct response in the operated eye but did exhibit an indirect pupillary response. The non-operated eye showed a direct but no indirect response. These results conclusively demonstrate for the first time that a true neuronal CPR does exist in chickens.
UNLABELLED: The effect of dopamine D2 receptor antagonists, such as chlorpromazine and haloperidol, on pupil size in awake subjects suggests that these drugs might also alter pupillary reflex dilation and pupil size during general anesthesia. Forty-seven patients undergoing lower abdominal surgery under combined epidural/general anesthesia were randomized to receive one of the 5 following open labeled drugs: 10 mL saline, 0.13 mg/kg ondansetron, 0.25 mg/kg metoclopramide, 0.5 mg/kg metoclopramide, or 0.02 mg/kg droperidol. Three measurements of reflex dilation were taken at 5-min intervals and after the last measurement (time 0) the drug was administered. Measurements were then taken 5, 10, 20, and 40 min after I.V. drug administration. Reflex dilation was induced by intermittent noxious stimulation of the C5 dermatome with a tetanic electric current (60-70 mamp, 100 Hz, 3-s duration) after a stable level of epidural analgesia had been established with 3/8% bupivacaine and maintained with a continuous infusion. Metoclopramide produced a small decrease in pupil diameter and transiently depressed reflex dilation, whereas droperidol decreased pupil size at 10 min and depressed reflex dilation throughout the 40-min study period. Maximal change in reflex dilation was -6.6 +/- 3.3 mm-sec after droperidol. Ondansetron had no effect on pupil diameter or reflex dilation. When pupillary diameter measurements are used to gauge opioid levels during experimental conditions or during surgical anesthesia, antiemetic medication acting on the dopamine D2 receptor should be avoided. IMPLICATIONS: Miosis is often considered an effect of opioid administration during general anesthesia, but other drugs, such as antiemetics, might produce a similar effect on the pupil. This study demonstrates that 2 antiemetics, droperidol and metoclopramide, constrict the pupil and block the pupillary dilation brought about by nociceptive stimuli.
Retinae from mouse embryos were transplanted to the midbrain of neonatal rats which were unilaterally enucleated at the time of transplantation. At maturity the host's remaining optic nerve was cut and the skull over the transplant was removed. Illumination of the transplant caused pupilloconstriction of the host eye, a response abolished by removal of the transplant or damage to the olivary pretectal nucleus which is the pupilloconstriction center of the brain stem. The degree of constriction correlated with the intensity of transplant illumination. Using mouse-specific monoclonal antibodies, we demonstrated that the grafts projected only to areas of the brain stem normally innervated by the eye. The density of label in the olivary pretectal nucleus did not, however, correlate with the briskness of the graft-mediated pupillary reflex. In summary, this study shows that ectopic neural xenografts are capable of making specific connections which can drive an appropriate response to a natural stimulus in the host animal. While important in showing the ability of transplants to make specific connections, this study also provides a simple assay system for examining conditions which may influence the efficacy of host innervation by the transplant.
The effects of some antimuscarinic compounds on oxotremorine-induced gastric damage, the pupil size and the pupillary light reflex have been studied in the rat. Unlike atropine, propantheline and methylscopolamine, pirenzepine is effective in preventing gastric erosions at doses much lower than those that affect pupillary reflex.
AIMS: To test the hypothesis that the alpha2-adrenergic agonist, dexmedetomidine, dilates the pupil and does not alter the pupillary light reflex of anaesthetized patients. METHODS: Eight volunteers were administered general anaesthesia with propofol, nitrous oxide and alfentanil. One hour and 25 min after induction of anaesthesia, a 45 min infusion of dexmedetomidine was begun, targeting a plasma concentration of 0.6 ng x ml(-1). Pupil size, pupillary light reflex amplitude, light reflex recovery time, and reflex dilation were measured before and during dexmedetomidine infusion. RESULTS: Dexmedetomidine produced no change in pupil size and light reflex recovery time, increased the light reflex from 0.30 +/- 0.14 to 0.37 +/- 0.12 mm and significantly reduced pupillary reflex dilation by 72 +/- 62%. CONCLUSIONS: These pupillary effects of dexmedetomidine in humans are difficult to reconcile with the findings obtained in cats and rats that have demonstrated a direct inhibitory effect of alpha2-adrenergic agonists on the pupilloconstrictor nucleus. The increase in the magnitude of the light reflex in response to dexmedetomidine does not necessarily involve an anxiolytic mechanism.
BACKGROUND: Regional anesthesia causes sympathetic blockade, vasodilation and higher skin temperature in anesthetized dermatomes. Measurement of skin temperature changes might provide a useful estimate of the level of caudal anesthesia in children. Pupillary reflex dilation (PRD) allows estimation of the sensory level during combined general/epidural anesthesia in adults, but has not been assessed in children. This study was designed to evaluate skin temperature and PRD as methods of estimating sensory level in children receiving combined general/caudal epidural anesthesia. METHODS: Twenty ASA I and II children aged 10 months-5 years were enrolled. Anesthesia was induced with sevoflurane and N2O in O2 and maintained with 1 MAC isoflurane and air in O2. Caudal epidural anesthesia was achieved by injection of 1 ml x kg(-1) 0.25% bupivacaine. Skin temperature was measured by rapid response infrared thermometry. PRD was measured using an ophthalmic ultrasound biomicroscope (UBM). The three criteria used to estimate sensory level were a drop in skin temperature of 0.5 degrees C between dermatomes, PRD of 50% and PRD of 0.2 mm. RESULTS: A drop in skin temperature of 0.5 degrees C between dermatomes allowed estimation of the sensory level in only 20% of patients. PRD of 50%, and PRD of 0.2 mm allowed estimation of the sensory level in 45 and 100% of patients, respectively. PRD was significantly greater above the T10 dermatome compared with L2 (P < 0.01). The maximum pupillary dilation was significantly greater in children over 2 years of age [1.3 +/- 0.8 mm sd)] compared with children less than two years of age [0.6 +/- 0.3 mm sd)]. CONCLUSIONS: Skin temperature cannot be used to estimate sensory level during combined general/caudal epidural anesthesia. PRD of 0.2 mm is sensitive to the loss of analgesia but is not clinically useful. PRD may be useful above 2 years of age.
A 22-year-old woman with definite multiple sclerosis had right-eye blindness with preserved direct and consensual pupillary reflex to light. The anatomy of the fibers inside the optic nerve did not give a satisfactory explanation of this phenomenon. On the other hand, this case appeared to support the idea of biochemical differences between the myelin of visual pathways and that of reflex pathways. Studies are necessary to confirm this hypothesis.
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With a modified method of infrared pupillography--especially developed for the use in clinical neurological routine diagnosis--the time course of the direct phasic pupillary light reflex in man was investigated under physiological and pathological conditions. The described method allows a high resolution of the time course of the light reflex and is superior to kinematographic as well as video-methods described so far. Normally the physiological time parameters are bilaterally symmetrical, also in cases of so-called physiological anisocoria. On the other hand in pathological anisocorias of various etiology pronounced side-differences and abnormal time parameters can be found. Also in cases of isocoria with clinically no abnormal findings of pupillomotor response pathological side-differences can be determined by infrared pupillography. Disturbances of the afferent arc, of the efferent arc and of combination of those as well as pupillary abnormalities to be located in the midbrain area, can be exactly analyzed and documented. Furthermore the method allows an objective documentation of the course in cases of dysfunction of the autonomic nervous system, like in intoxications, or to monitor drug-induced therapeutical measurements. The investigations and findings indicate that infrared pupillography, an objective method for analyzing the dynamics of the pupillary light reflex, is suitable for clinical neurological routing diagnosis.
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BACKGROUND: Pupil size is determined by an interaction between the sympathetic and parasympathetic divisions of the autonomic nervous system. Noxious stimulation dilates the pupil in both unanesthetized and anesthetized humans. In the absence of anesthesia, dilation is primarily mediated by the sympathetic nervous system. In contrast, pupillary dilation in cats given barbiturate or cloralose anesthesia is mediated solely by inhibition of the midbrain parasympathetic nucleus. The mechanism by which noxious stimuli dilate pupils during anesthesia in humans remains unknown. Accordingly, the authors tested the hypothesis that the pupillary dilation in response to noxious stimulation during desflurane anesthesia is primarily a parasympathetic reflex. METHODS: In six volunteers, the alpha-I adrenergic receptors of the iris musculature were blocked by unilateral administration of topical dapiprazole; six other volunteers were given unilateral topical tropicamide to block the muscarinic receptors in the iris. Desflurane anesthesia was subsequently induced in all volunteers. Sympathetic nervous system activation, with reflex dilation of the pupil, was produced by noxious electrical stimulation during 4% and 8% end-tidal desflurane, and by a rapid 4%-to-8% step-up in the desflurane concentration. Pupil diameter and the change in pupil size induced by a light stimulus (light reflex amplitude) were measured with infrared pupillometry. RESULTS: Dapiprazole drops produced a Horner's miosis, but pupils were equally small after induction of anesthesia. Pupillary dilation after noxious stimulation and desflurane step-up was identical in the unblocked and dapiprazole-blocked pupils. After tropicamide administration, the pupil was dilated and the light reflex was completely inhibited. Noxious stimulation nonetheless produced a slight additional dilation. CONCLUSIONS: During desflurane anesthesia, pupillary dilation in response to noxious stimulation or desflurane step-up is not mediated by the sympathetic nervous system (as it is in unanesthetized persons). Although inhibition of the pupillo-constrictor nucleus may be the cause of this dilation, the mechanism remains unknown.