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Bilateral angle-closure glaucoma in association with the acquired immune deficiency syndrome.

Two homosexual men, 35 and 42 years old, had bilateral acute angle-closure glaucoma in association with the acquired immune deficiency syndrome. In one patient, the angle-closure attack was the initial manifestation of AIDS. Choroidal effusion with secondary anterior rotation of the ciliary body at the scleral spur appeared to be the pathophysiologic mechanism. Pupillary block, angle crowding, and inflammatory synechial angle closure must be differentiated from anterior rotation of the ciliary body as the mechanism of the angle closure to provide optimal treatment. Whereas primary angle closures are treated with miotics and iridectomy, secondary angle closure may be worsened with this treatment. Cycloplegics and, if necessary, drainage of suprachoroidal fluid may be curative in AIDS-related angle closure associated with a choroidal detachment. Both patients died before the long-term efficacy of this treatment could be assessed.

Acquired Immunodeficiency Syndrome↗

Liposomes are effective carriers for the ocular delivery of prophylactics.

Liposomes containing acetylcholinesterase were prepared by the freeze-drying method. The multilamellar morphology of the vesicles was revealed by freeze-fracture electron microscopy and their size distribution was determined by quasi-elastic light scattering. The vesicle diameters were in the range of about 0.2-4.0 micron. The liposome preparations were tested for their ocular delivery of an entrapped cholinesterase enzyme in counteracting the miotic effect of diisopropylfluorophosphate (DFP), a prototype of a family of organophosphate poisons. The topical application of the enzyme-containing liposomes to the rabbit eye was found to confer a significant level of protection against DFP-induced miosis. In comparing the prophylactic effectiveness of different enzyme-bearing liposomes, positively charged vesicles were found to be more effective than either neutral or negatively charged vesicles. Although the precise protective mechanism is not clear, our in vitro studies indicate that DFP molecules freely associate with liposomes and tear fluid promotes the release of liposome-entrapped enzymes. Thus, it is conceivable that the enzyme-liposome complex may act somewhat like a sponge by sequestering DFP molecules which diffuse into the vesicle, and also by releasing the entrapped enzyme to combine with DFP, thereby neutralizing its in vivo toxic effect.

Acetylcholinesterase↗

Efferent discharge patterns in the ciliary nerve of rabbits and the pupillary light reflex.

Unitary discharges in the efferent ciliary nerves were studied in cervical sympathectomized rabbits. In all, 279 units were recorded and categorized, except 7 units, into the following 3 types from their responses to photic and other stimuli, i.e. type A (170 units), type B (42 units) and type C (60 units). Type A units were characterized by exhibiting excitatory response to ipsilateral eye illumination and the response was closely related to the luminance level. The type A was further classified into AI (excitation), AII (no change) and AIII (inhibition) on the basis of the response to contralateral illumination. It was inferred that the type A was functionally related to active pupilloconstriction. Type B units were characterized by showing an exclusively inhibitory response to ipsilateral and/or contralateral illumination and the inhibition was luminance-dependent. It was therefore assumed that the type B was concerned with active pupillodilation. Type C units were not responsive to light stimulus, though the type C displayed characteristic reflex response to mechanical or thermal stimulus within the receptive field. The reflexive response, however, was not mediated via the oculomotor nerve. In order to confirm the results of the unit analysis, pupillary light reflex was examined. In particular, the consensual reflex varied depending upon individual rabbits. Namely, one became miotic, another mydriatic and a third remained uninfluenced, which corresponded well with the response pattern of the light-sensitive units.

Accommodation, Ocular↗

Horner'sy syndrome and its significance in the management of head and neck trauma.

The history, mechanism and aetiology of Horner'sy Syndrome is presented and the pharmacology of the pupil is discussed. The case reported is a rare combination of Horner's Syndrome in a patient who sustained bilateral fractures of the mandible and a chest injury. It is emphasised that the miotic changes in Horner's Syndrome, in combination with head injuries can lead to confusion in diagnosis and the potential anaesthetic hazards and their influence on the management of the facial injury are outlined.

Adolescent↗

Neurogenic mechanisms in control of the rabbit iris sphincter muscle.

The iris sphincter muscle is supplied with cholinergic, adrenergic and substance P-containing nerve fibers, all with a possible role in the control of pupil size. The functional significance of the various nervous components in the rabbit iris sphincter muscle was examined in vitro and in vivo. The contractile response to electrical stimulation is composed of several contractions, occurring along different time scales. Single pulse stimulation produced an atropine-sensitive twitch. Pulse train stimulation revealed two successive atropine-sensitive twitches followed by a slow, long-lasting contraction, sensitive to Spantide, an antagonist of tachykinins such as substance P. A guanethidine- and phentolamine-sensitive contractile response to pulse train stimulation could be demonstrated in the presence of both atropine and Spantide. Only the Spantide-sensitive response could be completely exhausted by prolonged electrical stimulation. In vivo, neither the adrenergic nor the substance P-containing nerve fibres appeared to contribute to the miotic response to light since Spantide and guanethidine were without effect. This response was inhibited by atropine only.

Animals↗

Effect of thymoxamine on the human pupil.

The specificity of thymoxamine, an alpha-adrenoceptor antagonist was determined from in vitro organ bath studies using isolated preparations of canine saphenous and portal mesenteric veins. It was found that thymoxamine interacts mainly with postjunctional alpha-adrenoceptors. The miotic effects of topical thymoxamine hydrochloride were measured in normal human eyes using infrared pupillography. The effects of five different concentrations of thymoxamine were measured over time. Time-response and concentration-response relationships were calculated. The maximal pupillary response occurs at 60 min after instillation of the drug and has a half-life of 10 hr. The minimum effective concentration of thymoxamine is 0.01%, and the maximum effective concentration is 1.3%. Thymoxamine's properties could make it a clinically useful drug to diagnose angle-closure glaucoma, and also to reverse drug-induced mydriasis.

Adult↗

The pupillary effects of opioids.

Morphine's miotic action on the pupil is an easily recognizable and quantifiable effect in man. The neural pathways responsible for regulating pupil size are reasonably well defined. Yet, the mechanisms behind this and related effects of opioids on the eye in humans and laboratory animals have just begun to be explored. In this review, we have attempted to organize the available information on pupillary actions of opioids, emphasizing the dynamic nature of the responses, their species specificity, possible mechanisms of action, and the recently discovered development of tolerance to these actions. Our current knowledge regarding differences among the opioids, the effects of endogenous opioid peptides and the role of the various opiate receptor subtypes in pupillary effects is also summarized.

Animals↗

Ocular pharmacokinetics of dapiprazole.

Dapiprazole is a drug having specific alpha 1 adrenergic blocking properties. Following topical instillation on the eye, it crosses the corneal epithelium reaching high concentrations in the ocular tissue and producing a prompt miotic and hypotensive effect. The high concentration ratio between ciliary bodies and iris versus aqueous humor suggests a peculiar affinity for these structures containing adrenoceptors of the alpha type. The very low concentrations in the plasma, as compared to those after systemic administration, and in the fellow eye indicate that the systemic absorption is negligible.

Administration, Topical↗

Malignant glaucoma.

The term "malignant glaucoma" referred originally to a rare and highly feared form of glaucoma occurring in certain postoperative patients. Over time the concept of the disease was expanded to include a group of angle closure glaucomas unresponsive to traditional miotic or filtering therapy. The haphazard lumping of many disease entities under such an umbrella term has caused confusion, which we attempt to resolve through a mechanistic approach to elucidating the pathogenesis of malignant glaucoma based on the anatomical location of obstruction to normal aqueous flow; surgical treatments are suggested based on the pathogenesis. Attention is drawn to the role of the vitreous and anterior hyaloid in combination with a block to normal aqueous circulation, redirection of its flow, high intraocular pressure and vitreous swelling in precipitating malignant glaucoma and creating a vicious circle to maintain it. Surgical management is directed to correcting the obstruction to normal aqueous flow and removing aqueous accumulated in the posterior chamber, vitreous or suprachoroidal space.

Eye Diseases↗

Aging, senile miosis and spatial contrast sensitivity at low luminance.

The purpose of this study was to determine how aging affects spatial contrast sensitivity at low light levels and to examine whether senile miosis, which reduces retinal illuminance in the aged eye, underlies any observed sensitivity loss. Contrast thresholds for targets having a range of spatial frequencies were measured in young (n = 13, M age = 24) and older (n = 11, M age = 73) adults who were free from identifiable ocular pathology. Measurements were carried out at three luminance levels spanning a three log unit range. Results indicated that older adults' loss in contrast sensitivity not only increased with increasing spatial frequency, but also became more pronounced with decreases in luminance level. Additional threshold measurements where pupil diameter was varied indicated that senile miosis was not responsible for older adults' loss in spatial vision at any level tested. Rather, older adults' miotic pupil tended to have a positive effect on their spatial vision in that it slightly improved their contrast sensitivity.

Adult↗

Surgical treatment of spontaneous cerebellar hemorrhage.

UNLABELLED: Spontaneous cerebellar hemorrhage accounts for 5%-10% of intracerebral hemorrhage in most series. From June 1979 to June 1983 we had 26 surgical cases of spontaneous cerebellar hemorrhage. There were 15 men and 11 women. The typical history was sudden onset of severe headache, vomiting, dizziness, and inability to walk. Disturbance of consciousness was usually a late feature. Common signs were truncal ataxia, nystagmus, conjugate eyeball deviation, small miotic pupils with or without light reflex and abducens palsy. Surgical indications are (a) disturbance of consciousness, (b) signs of brainstem compression and (c) hematoma with transverse diameter greater than 3 cm. The overall surgical mortality was 34.6%. Twenty-two patients underwent suboccipital craniectomy to evacuate hematomas with or without ventriculostomy; mortality rate was 27%. Four patients underwent ventriculostomy only; mortality was 75%. Causes of death were (a) brainstem failure, six patients; (b) airway obstruction, one patient; (c) chest infection, one patient; (d) chronic renal failure, one patient. CONCLUSION: (a) suboccipital craniectomy to evacuate the hematoma is the most effective procedure where treatment is indicated; (b) the clinical recovery of the survivors show that 31% return to work, 38% are moderately disabled but take care of themselves, and 31% remain dependent on others; (c) deeply comatose patients may still benefit from early operation.

Adult↗

Ocular responses to leukotriene C4 and D4 in the cat.

The effects of leukotriene C4 (LTC4) and D4 (LTD4) on the iridial smooth muscles, intraocular pressure, blood-aqueous barrier and regional blood flow in the eye have been studied in cats. The test compounds were injected into the anterior chamber. Both LTC4 and LTD4 caused a dose-dependent constriction of the pupil, the agents being about equipotent. The effect on the iridial sphincter muscle was not dependent on nerve conduction, cyclo-oxygenase products or muscarinic receptors. Maximal constriction was achieved with 0.1-1 microgram of the test compounds. The smallest dose to induce a decrease in pupil diameter was 0.01 microgram. After intracameral injection of 4 micrograms the miotic response was markedly delayed. This indicates that in high concentrations LTC4 and LTD4 probably also stimulate the iridial dilator muscle. The blood flow in the anterior uvea decreased after intracameral injection of 4 micrograms LTC4/LTD4. Smaller doses had no clear effect. There was no effect on the blood-aqueous barrier as judged from the aqueous humor protein concentration. The intraocular pressure decreased slightly after injection of the test compounds.

Animals↗

Interaction between nicotine and endogenous opioid mechanisms in the unanesthetized dog.

Nicotine produced a distinct reproducible syndrome in the conscious dog when injected intravenously or intracerebroventricularly. Intravenously administered nicotine (40 micrograms/kg/min for 20 minutes) increased cardiac and respiratory rates and produced analgesia, miosis, hypothermia, behavioral restlessness and emesis. When microinjected into the third cerebral ventricle, nicotine (100-200 micrograms) similarly increased cardiac and respiratory rates and pupillary diameter; and produced behavioral restlessness, emesis, erratic analgesia and maintained wakefulness and a desynchronized EEG. Microinjection of nicotine (5-25 micrograms) into the periaqueductal gray failed to alter any of the parameters studied. Intravenous pretreatment with the opioid antagonist naltrexone (2 mg/kg) influenced the action of intravenous nicotine on certain physiological systems. While naltrexone alone produced a significant degree of tachycardia, miosis, and analgesia, it potentiated the tachypnea and antagonized the miotic response evoked by nicotine. Methionine-enkephalin was detected in perfusates obtained from the lateral cerebral ventricles of conscious dogs. Nicotine produced a non-significant decrease in enkephalin levels. These observations suggest that there are interactions between endogenous opioid and nicotinic processes. However, they are complex and may differ from one functional system to another.

Animals↗

Pupillary response to atrial natriuretic factor in rabbits.

This study was designed to evaluate the pupillary and intraocular pressure (IOP) response to exogenously administered atrial natriuretic factor (ANF) in rabbits. Dose-response studies were conducted by administering intracameral (i.c.) ANF (0.1-5 micrograms). The effect of route of administration was evaluated by administering ANF (5 micrograms/kg) intravenous (i.v.) subcutaneous (s.c.) and intraperitoneal (i.p.). In a final study, normal rabbit serum or ANF antiserum were administered i.c. In all studies, pupillary diameter (PD) and IOP were evaluated. Intracameral administration of ANF (0.1-5 micrograms) produced a significant (P less than 0.01) dose-dependent unilateral miosis without affecting IOP. Peripheral (i.v., s.c., i.p.) administration ANF did not affect PD or IOP. Finally, ANF antiserum did not affect PD significantly. These data suggest that ocular, but not circulating ANF may contribute to regulate pupillary function. The mechanism of the miotic response to ANF probably involves interactions with other autonomic neurotransmitters because immunoneutralization of endogenous ocular ANF was without measurable effect.

Animals↗

Loss of supersensitivity of the cat eye to carbachol at prolonged periods after ciliary ganglionectomy.

Adult female cats (2.4-2.8 kg) underwent surgical removal of the left ciliary ganglion under pentobarbital anesthesia. Twenty-one, 560 and 616 days later, pupil size of both left and right (control) eyes was measured in response to progressively increasing doses of carbachol applied topically. By 21 days after denervation, ganglionectomized eyes showed marked supersensitivity to the miotic effects of pilocarpine and carbachol. By 560 days, however, responsiveness of the denervated eyes to lower and intermediate doses of carbachol was the same as that of contralateral control eyes, while responsiveness to higher doses was significantly reduced. Responsiveness to both lower and higher doses of carbachol was significantly less than that of the controls on the 616th day. Ganglionectomized eyes showed no pupillary response to light 14, 562, or 620 days after surgery. Histochemical analysis of iris tissue collected from eyes of these cats 720 days after ganglion removal revealed an almost complete absence of acetylcholinesterase-containing nerve fibers on the denervated side. These findings indicate that the return to normal or lower sensitivity to carbachol of denervated eyes at prolonged periods after ciliary ganglion removal is not due to significant cholinergic reinnervation of the iris sphincter muscle.

Acetylcholinesterase↗

Neuropeptide Y suppresses the neurogenic inflammatory response in the rabbit eye; mode of action.

Ocular injury in the rabbit causes miosis and breakdown of the blood aqueous barrier (aqueous flare response, AFR), reflecting a sensory nerve-mediated inflammatory response, elicited by the release of tachykinins and calcitonin gene-related peptide (CGRP) from C-fibers. Neuropeptide Y (NPY) occurs in sympathetic fibers in the eye. The study was designed to examine whether NPY and related peptides interfere with the inflammatory response to ocular injury in the rabbit in vivo. The isolated rabbit iris was studied with respect to NPY binding sites and second messenger coupling. The AFR and the miotic response to a standardized injury (infrared irradiation (IR) of the iris) were suppressed dose-dependently by NPY (0.01-1.0 nmol) injected intravitreally 30 min prior the trauma. The treated eye was compared with the contralateral eye, which received 0.9% saline and IR. The Y1 receptor agonist [Pro34]NPY, the Y2 receptor agonist NPY 13-36 and the structurally related peptide YY (1 nmol each) suppressed the AFR in response to IR. Injection of either NPY or the Y1 and Y2 receptor agonists (0.3 nmol each) suppressed the AFR evoked by exogenously applied CGRP (0.15 nmol). Saturation studies with 125I-NPY revealed both high and 'moderate' affinity binding sites in the iris. The Bmax values were 26 and 321 fmol/mg protein, respectively. NPY suppressed the forskolin-stimulated adenylate cyclase activity (IC50 value 19 nM). NPY did not affect basal or noradrenaline-induced accumulation of inositol phosphates in the iris. In conclusion, the rabbit iris seems to be rich in NPY receptors linked to inhibition of adenylate cyclase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗

Heightened cholinergic responsiveness in IgE-producing rabbits.

Atopic humans express an array of autonomic nervous system abnormalities. An animal model of IgE-mediated allergy was herein employed to determine if the induction of an IgE antibody response would affect autonomic responsiveness. Rabbits were immunized so as to selectively produce IgE antibodies, and their pupillary miotic and mydriatic responses to cholinergic and alpha adrenergic stimuli, respectively, were determined. IgE-producing rabbits exhibited hyperresponsiveness to cholinergic but not alpha adrenergic stimulation, a pattern resembling that seen in nonasthmatic atopic humans. Repeated sublethal anaphylactic episodes induced in three IgE-producing rabbits did not affect the pattern of autonomic responsiveness when compared to controls challenged with saline, despite clear evidence of increased plasma histamine levels immediately after antigen challenges in the IgE group. This study indicates that elicitation of an IgE antibody response is associated with the concomitant development of cholinergic hyper-responsiveness.

Animals↗

Unilateral impairment of pupillary response to trigeminal nerve stimulation in cluster headache.

The pupillary constriction induced ipsilaterally by transcutaneous electrical nerve stimulation (TENS) of the infratrochlear nerve was measured, using an electronic pupillometer, in 26 episodic cluster headache (CH) and 15 migraine sufferers tested during an attack-free period and in 16 healthy controls. In controls, TENS gave rise to a miosis which was slow in onset and long-lasting in duration, and which was comparable to that mediated by tachykinins in animals. A similar miotic response was bilaterally observed in migraine patients and in CH patients examined during the inactive phase. In CH sufferers during the cluster period, TENS only elicited a normal pupillary constriction in the asymptomatic eye, whereas the resulting response in the symptomatic eye was markedly decreased. Although the exact mechanism underlying the dysfunction remains to be clarified, these results seem to indicate that ocular trigeminal pathways are involved in CH.

Adolescent↗