Improving diagnostic acumen in pupillary evaluation: a review for the primary care physician.

Many primary care physicians perform only a superficial pupillary evaluation as part of the physical examination. The authors review several maneuvers that require no special equipment and help to improve diagnostic yield. The "swinging flashlight" test aids in detecting a relative afferent pupillary defect. When a patient has anisocoria, the initial diagnostic challenge is to determine which pupil is abnormal. Comparing the extent of pupillary inequality under both dim and bright illumination almost always identifies the dysfunctioning pupil(s) and narrows the differential diagnosis. The authors compare third-nerve palsy and Horner's syndrome as causes of anisocoria and review light-near dissociation, another important category of pupillary dysfunction. This latter phenomenon is seen in the Argyll Robertson pupil, the dorsal midbrain syndrome, and the tonic pupil syndromes. Pupillary size and activity are key diagnostic parameters in the evaluation of patients in coma. Structural and mechanical iris defects are also frequently responsible for pupillary anomalies.

Recovery of pupillomotor function after cataract surgery.

To determine the effect of cataract surgery upon pupillomotor function, we studied the pupillary response to light in four subjects who had extracapsular cataract extraction with implantation of an intraocular lens. A video infrared pupillometer was used to record pupillary responses 6-20 weeks after surgery. Non-operated eyes were compared to operated eyes in each subject. Amplitudes and peak velocities of constriction for operated versus non-operated eyes differed over a small range (2-14%). No evidence of dilation lag or segmental palsy was found in the operated eyes. The latency of constriction was not prolonged. We conclude that pupillomotor function can be expected to recover in aviators who require routine cataract surgery, and that visual disability due to a poorly dilating or constricting pupil should not be an overriding concern.

Hyperglycemia does not modify the pupillary effects of mu and kappa opiate agonists in mice.

The effects of mu and kappa opiate agonists were assessed on the pupillary size in normoglycemic and hyperglycemic conditions in mice. The mu agonists used were, morphine (10, 30 and 100 mg/kg), fentanyl (50, 100 and 150 micrograms/kg) and sufentanil (5, 10 and 20 micrograms/kg). The highly selective kappa opiate agonists used were, U-50488H and U-69593 (30 mg/kg). Chronic hyperglycemia was induced by streptozotocin injection (200 mg/kg i.p) 7-8 days before the experiment. Acute hyperglycemia was induced by intraperitoneal glucose (5 g/kg i.p) injection at the time of subcutaneous injection of opiates. In the normoglycemic mice, the mu agonists produced significant mydriasis (P less than 0.05), while kappa agonists had no effect on the pupil. However, both acute and chronic hyperglycemic condition did not affect the mydriatic ratio of the mu opiate agonists. These results indicate that mu opiate receptors induce mydriasis in mice and suggest that the hyperglycemia is not the mechanism involved in the opiate induced mydriasis in mice. With the dose of kappa agonists used, the involvement of kappa receptors in the pupillary effects in mice were not clear. These results support the hypothesis that hyperglycemia is not the primary mechanism for the altered sensitivity of opiates in the animal models of diabetes.

Vegetative imbalance in migraine. A dynamic TV pupillometric evaluation.

In this study we investigated the variations of pupillary diameter obtained in different experimental conditions (dark/light adaptation, light reflex, sural nerve stimulation) in a group of migraine patients with unilateral location of pain in almost all the attacks and in healthy controls by means of a TV pupillometric device. The data obtained seems to document the existence in migraine of unbalanced vegetative function ascribable either to a strong sympathetic activity or to a parasympathetic deficiency. Moreover, an involvement of central integrative pathways regulating pupil functioning cannot be excluded.

Two cases of Hashimoto's thyroiditis with pupillary disturbances.

Two cases of Hashimoto's thyroiditis with pupillary disturbances are reported. Case 1 was a 58-year-old housewife, displaying pandysautonomia. Case 2 was a 65-year-old housewife, suffering from chronic polyneuropathy and polymyopathy. Both patients showed similar pupillary disturbances, suggesting both sympathetic and parasympathetic postganglionic denervation of the pupil. Hashimoto's thyroiditis may have caused the pupillary disturbances in association with generalized polyneuropathy or pandysautonomia.

Argon laser-induced ocular hypertension: animal model of ocular inflammation.

There is substantial evidence that prostaglandins (PG's) mediate acute elevations of intraocular pressure (IOP) due to laser irradiation of the iris. In the present study, we determined the optimal laser parameters needed to produce the maximal rise in IOP in anesthetized rabbits. Application of argon laser (0.75 watts, 0.5 sec. duration, and 8 spots of 500 micron size) to the iris of pigmented rabbits elicited an acute rise in IOP and miosis accompanied by an increase in aqueous protein concentration. This response was followed by a delayed ocular hypotension that lasted for more than 3 days and returned to baseline by day 5. The onset of ocular hypertension occurred within 15 min. and remained elevated for at least 90 min. The laser induced rise in IOP was related more to the number of laser spots applied to the iris than to the intensity of the total laser energy utilized. Pretreatment with either indomethacin or flurbiprofen produced a dose dependent inhibition of ocular hypertensive response and significantly reduced aqueous protein concentration. Indomethacin (0.01-30 mg/kg) was administered intraperitonially 1 hr. before laser treatment and flurbiprofen (0.03-0.3%) was administered topically 45 and 15 min. prior to laser application. The hypertensive response was reduced by more than 90% of control after both drugs, whereas the delayed hypotension was significantly antagonized only at the highest dose of indomethacin. Neither indomethacin nor flurbiprofen altered the maximum miotic response to laser irradiation of the iris. However, 0.3% flurbiprofen and 30 mg/kg indomethacin significantly increased the recovery rate of the miotic pupil. The results of this study support the contention that argon laser induced ocular hypertension may provide a quantitative assessment of inhibition of prostaglandin mediated responses.

Auditory evoked responses in the management of acutely brain-injured children and adults.

In recent years, the role of auditory evoked responses (AERs) in the intensive care unit (ICU) setting has expanded dramatically for both pediatric and adult brain-injured patient populations. AERs have unique value in early identification and evaluation of peripheral auditory dysfunction that can result directly from head trauma or as a consequence of intensive medical therapy (such as prolonged intubation and ototoxic drugs). AERs can also be applied in evaluating and monitoring neurologic status during the acute period following a severe brain injury, similar to their common intraoperative use as a neurophysiologic monitor. This paper reviews factors influencing measurement of AERs in the ICU, including the effect of (1) intensive medical therapy (e.g., neuromuscular blockers, sedatives, barbiturates, aminoglycosides, and loop diuretics); (2) coma; and (3) computed tomography confirmed temporal bone fracture. The rationale for monitoring neurologic status with AERs in this setting is presented and supported with original group data. Important points are illustrated with selected case reports.

Effects of routine pupillary dilation on functional daylight vision.

The visual acuity of 100 patients between the ages of 16 and 66 years, seen for routine ophthalmologic examination, was measured before and after dilation. All patients had a predilation visual acuity of 20/40 or better. Postdilation binocular visual acuity using the patients' usual correction was measured first in the office and then outdoors, both with the patient's back to and the patient facing the sun, with and without the aid of postmydriatic sunglasses. Twelve percent experienced disabling photophobia even with the use of postmydriatic sunglasses, with 3% having significant objective visual loss defined as 20/50 or worse. No objective visual loss was found in 30 controls examined outdoors before dilation, without sunglasses. We recommend that patients who have experienced significant photophobia with dilation in the past, or who have never before undergone dilation, make arrangements for transportation after a dilated examination.

Paradoxic pupillary phenomena. A review of patients with pupillary constriction to darkness.

The presence of pupillary constriction to darkness is said to be a useful indicator of retinal disease. However, it is also associated with optic nerve disease. The phenomenon has been reported in patients with congenital stationary nightblindness, congenital achromatopsia, bilateral optic neuritis, and dominant optic atrophy. We have observed this response in additional disorders, including anomalies of the optic nerve development, congenital nystagmus, and a variety of diseases affecting the retina. Notably, four of our patients with strabismus and amblyopia, but without apparent retinal or optic nerve disease, have also demonstrated this paradoxic pupil response. While the mechanism for pupillary constriction to darkness remains unclear, the finding of this response in patients without retinal or optic nerve abnormalities questions its value as a localizing sign.

Dysfunction of the sympathetic nervous system in cluster headache.

Ocular sympathetic function was studied in 13 cluster headache patients during and between attacks and several weeks or months after attacks had subsided. The pupillary response to tyramine eyedrops and facial sweating and flushing in response to body heating and to the taste of chilies were also investigated during remission. Pupillary dilatation lag on the symptomatic side persisted between bouts and correlated significantly with loss of thermoregulatory sweating in the lower part of the forehead. In six patients in remission, pupillary dilatation in response to tyramine eyedrops was impaired on the symptomatic side, whereas five patients showed no sign of ocular sympathetic deficit. These findings indicate that incomplete sympathetic deficit persisted on the symptomatic side in a subgroup of cluster headache patients during remission. In most of this subgroup the pattern of sympathetic deficit was consistent with impaired function of postganglionic cervical sympathetic fibres.

Pupil responsiveness in cluster headache: a dynamic TV pupillometric evaluation.

In this study the variations in pupil diameter induced by different stimuli (dark-light adaptation, light reflex, electric stimulation of the sural nerve) were investigated in episodic (in the active or remission phases) and in chronic cluster headache (CH) patients. Pupil size monitoring was performed with a monocular, infrared TV pupillometer, and sural nerve stimuli were applied after the pain threshold had been measured as the flexion reflex threshold of the biceps femoris muscle (RIII reflex). The results were compared with those obtained in patients with "peripheral" (third neuron) Horner's syndrome and in healthy sex- and age-matched controls. On the symptomatic side we found an impairment of pupil response to light flashes and nociceptive stimuli; similar findings were sometimes evident on the pain-free side, too. These results substantiate previous observations that in cluster headache a dysfunction of the integrative central nervous system pathways also exists intercritically and mostly bilaterally, involving both autonomic regulation and pain perception mechanisms.

Cluster headache: combined assessment with pupillometry and evaporimetry.

Twenty-nine patients with cluster headache have been examined with the pupillometer and the evaporimeter. Pupils were dilated by sympathicomimetic drugs instilled into the conjunctival sacs, and responses of the two sides were compared. Forehead sweating was stimulated by body heating and by pilocarpine injection, and sweat evaporation on the two sides was compared. Most patients demonstrated the known patterns of hyposecretion on heating, of pilocarpine supersensitivity, and of deficient pupillary dilatation on OH-amphetamine stimulation on the symptomatic side and a supersensitivity of this pupil to phenylephrine. There were deviations from the rule for all methods of testing. Sixteen patients demonstrated a typical supersensitivity response of the pupil and of the sweat glands on the symptomatic side. Six patients had no such response, and seven patients had a discrepancy between the pupillary and the sweat gland response to stimulation, supersensitivity being present in one system only. There was a high degree of concordance between the results of the various methods of examination.

Chronic paroxysmal hemicrania. XIII. The pupillometric pattern.

Pupillometric studies were carried out in eight patients with chronic paroxysmal hemicrania (CPH) and in age- and sex-matched controls in the basal condition and after instillation of 2% tyramine (CPH, n = 5; controls, n = 17), 1% OH-amphetamine (CPH, n = 6; controls, n = 12), and 1% phenylephrine (CPH, n = 6; controls, n = 17). The pupil on the symptomatic and non-symptomatic sides in CPH patients was significantly smaller in the basal condition than in controls, particularly on the symptomatic side. The mydriatic responses to pharmacologic stimulation were essentially similar on the symptomatic and non-symptomatic sides. An evaporimetric study of the forehead sweat glands, using the body heating and pilocarpine tests, was also carried out in these patients and in age- and sex-matched controls. "Early", "intermediate", and "late" measurements demonstrated symmetry of forehead sweating. The findings for both methods of examination thus contrast with those in cluster headache patients. Pupillometric and forehead sweating patterns therefore suggest differences in the pathogenesis of the two headache entities. These tests may be used to distinguish CPH and cluster headache clinically.

Enhanced specificity of prognosis in severe head injury.

Data from 523 patients admitted to the Medical College of Virginia with severe head injury and known 6-month outcomes were analyzed in order to determine the optimal combination of early-available prognostic factors. Twenty-one prognostic indicators noted in the emergency room at admission were used to predict outcomes into four categories: good, moderately disabled, severely disabled, or vegetative/dead. A combination of the patient's age (in years), the best motor response (graded in the usual six-point scale), and pupillary response (in both eyes) was found to be the most accurate indicator. The model correctly predicted outcome into one of the four outcome categories in 78% of cases ("specifically accurate predictions"). If predictions into an outcome category adjacent to the actual outcome were accepted, this model was accurate in 90% of cases ("grossly accurate predictions"). A set of three simple graphs based on this model can be used for rapid early estimation of probable outcome in a severely head-injured patient at admission.

Determining interrater reliability of nurses' assessments of pupillary size and reaction.

Pupil changes provide vital information related to the cause and location, and at times, severity of disease processes which alter level of consciousness. Size and reactivity are sensitive to a variety of influences including local eye damage, functional state of brainstem, local systemic drugs, seizures and anoxia. Therefore, accurate measurement of pupillary size and reactivity is essential. The purposes of this study were to determine if pairs of nurses (1) achieved the same measurement of pupil sizes with and without an objective measure, and (2) selected the same descriptor for pupillary reaction to light. Sixty-eight pairs of nurses employed in adult and pediatric units of a large teaching hospital participated in the study. Interrater reliability of pupillary assessment of 136 nurses was determined. There was no significant difference in the reliability of nurses assessing pupillary size regardless of whether they used a penlight pupil gauge to measure or used observation without a pupil gauge. Agreement among the nurses on the pupillary size was high. Agreement on the pupillary reaction, however, was poor to good.

Binocular luminance summation (BLS) in esotropic and exotropic kittens

Normal kittens showed a gradual increase from 17.6% to 25.5% of BLS with aging from the fifth week to the ninth. Young kittens showed significantly less BLS than do adult ones (p < 0.1), There was significant difference of BLS between exotropic and normal kittens or alternating and non-alternating strabismic ones. However, there was a significant diftrence between esotropic and normal ones (p < 0.1). These results suggested that the BLS can be used as a index for the extent of total field from both eyes.

Pupillary sympathetic hypofunction and asymmetry in muscle contraction headache and migraine.

Pupillary autonomic dysfunction and right-left differences were investigated in muscle contraction headache (MCH) and migraine, by means of biocular infrared videopupillography (biocular Iriscorder). The study was performed on 36 patients with MCH or migraine and on 23 healthy controls. The pupillary area before light stimuli and maximum dilatation velocity of pupils, in MCH patients and migraineurs, showed significant differences from those of controls. Pupillary asymmetry was observed in both headache categories. The behavior of MCH pupils to light stimuli under dark conditions was rather similar to that of migraine pupils. Both pupillary sympathetic hypofunction and subtle anisocoria were present not only in patients with migraine but also in those with MCH.