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The effects of beta sympathetic drugs on positive accommodation (accommodation for near vision) were studied in vervet monkeys. Isoproterenol, a beta sympathetic stimulator, depressed the positive accommodation function. It was not a complete antagonist since 3 to 4 diopters of accommodation remained. Only atropine, a parasympathetic blocker, could abolish these 3 to 4 D as well as the entire function. In many of the experimental animals, positive accommodation function was biphasic. The initial component had a flatter slope, lower amplitude, and lower threshold of stimulation than the second. The transition point of the components was between 2 and 4 D. Beta sympathetic stimulation appeared to abolish selectively the second component while parasympathetic inhibition abolished both components. It appeared that peripherally, parasympathetic inhibition was a more potent and thus more important mechanism in antagonizing positive accommodation than beta sympathetic stimulation.

The effects of alpha sympathetic drugs on positive accommodation (accommodation for near vision) were studied in 15 vervet monkeys. Levarterenol 5%, a predominantly alpha stimulating drug, when applied topically in one eye produced a depression in accommodation in that eye. This response appeared to be mediated through beta receptor sites, since it was inhibited by propranolol, a beta sympathetic antagonist, rather than phentolamine, an alpha inhibitor. Larger topical doses (10%) or subconjunctival administration of 5 mg or more, when given unilaterally, depressed accommodation bilaterally without dilating the contralateral pupil. These effects appeared to be indirectly induced. It would seem from our studies that stimulation of alpha sympathetic receptors served no important function in antagonizing positive accommodation.

INTRODUCTION Recent electron microscopic studies have demonstrated the presence of two distinct types of muscle fiber, Fibrillenstruktur and Felderstruktur,1 in the extraocular muscles of guinea pig,2 cat,3 and man.4 In the Fibrillenstruktur fibers, the myofibrils have a punctate appearance, and the sarcoplasmic reticulum surrounds clearly the individual fibrils. The Felderstruktur fibers, on the other hand, have larger myofibrils which are not regularly separated from each other and appear to be fused together. Physiologically, the Fibrillenstruktur fibers appear to be associated with relatively rapid twitch responses, whereas the Felderstruktur fibers respond to stimulation with prolonged contracture.3There are, in addition, two kinds of nerve endings in the extraocular muscles which can be histochemically differentiated by cholinesterase staining; these are the "en plaque" and "en grappe" endings.2-7 The "en plaque" endings stain intensely and show the same configuration as the subneural apparatus of motor end-plates in

INTRODUCTION The development of iris cysts along the pupillary border has been associated with the topical administration of miotics. The incidence of these lesions is particularly high in young patients treated for accommodative esotropia with the long-acting cholinesterase inhibitors, eg, isofluorophate (Floropryl, DFP) and echothiophate iodide (Phospholine Iodide). A number of studies have been performed to elucidate the mode of action of these agents in the therapy of strabismus.1,2 These investigations have shown that the therapeutic effectiveness of the miotics in the management of esotropia cannot be accounted for on the basis of increased depth of focus resulting from pupil constriction. It should be possible, therefore, to use a mydriatic in conjunction with the miotic and still achieve the desired result. The preliminary clinical experiences of one of us (G. M. B.) have shown that a regimen of 10% phenylephrine (t.i.d.) with echothiophate tended to inhibit cyst formation.2

Study of a diverse group of supranuclear muscle affections has revealed certain unusual and, in some instances, characteristic phenomena. The technique has been described in previous publications.1,2 Frequently noted has been a spindle pattern of innervation in the extraocular muscles in which the discharge builds up to a peak and then declines in a rhythmic fashion. This pattern is similar to that seen in the electroencephalogram during sleep and barbiturate hypnosis. Motor spindles were also observed in sleep (Fig. 1) and have been encountered in gaze palsies or deviations. The presence of such spindles suggests the existence of a supranuclear disturbance of motility. The location and nature of the generator for such potentials is of course unknown. It may be suggested that the reticular formation is involved in their genesis. Pendular nystagmus shows a similar pattern. Saccadic movements and innervation are also characteristic of gaze disturbances. A. CONJUGATE

This paper is one of a series of studies in vergence investigated by means of electromyography, parts of which have been previously reported.1,2 The present study is concerned with accommodative and fusional vergence.The technique has been fully described in previous reports.1-4 The energy levels of various positions have been determined with the integrator. I have deliberately inserted electrodes into only one muscle in many cases to minimize artefacts induced by multiple needle placements. The latter is a definitely limiting factor in evaluating fusional amplitudes and is conducive to blurriness of vision in the tested eye. Nevertheless, simultaneous studies of both medial and lateral rectus confirm the findings to be reported. The lateral rectus has often been selected for testing because the question of divergence is of considerable interest and because there is thus little interference with vision or examination. In some studies very fine electrodes (No. 31

INTRODUCTION During the past several years sufficient experience has been gained in the technique of electromyography of the human extraocular muscles to fairly appraise its usefulness.1-10 As a research tool it is of inestimable value in the analysis of the innervational basis of normal and disordered motility. Fundamental insights are being gained in the mechanisms maintaining normal extraocular muscle balance, so essential to binocular single vision. The sources of tonic innervation of eye muscle, although not well understood, now have become considerably clearer and may eventually be fully revealed in the course of analytic studies. The complex interrelationship of versions and vergences is being clarified, permitting a new understanding of the manner in which central adjustment of opposing sources of innervation is brought about. Through the study of varied types of pathologic involvement of the extraocular muscles it has been possible to make certain preliminary judgments concerning the nature

Electrophysiologic approaches to the analysis of innervation in ocular motility have made evident the need for quantitative techniques.1 That need has now been satisfied with the development of a full wave integrator and differentiator in one instrument. The former provides an integration of the energy developed in specific time intervals. The height of the condenser discharge is exactly proportional to the energy accumulated and discharged within these intervals. This discharge is fed into a second beam of the dual beam oscilloscope or can be written out on an ink writer. A simple linear measurement gives the desired information. The frequency response is from 5 to 1000 cps—a spectrum deemed adequate for electromyographic potentials.The importance of this advance cannot be underestimated, since the evaluation of neuromuscular activity involves consideration of both amplitude and frequency. Inspection methods are inadequate to perform this task satisfactorily.In addition, the differentiator provides an

Considerable interest attaches to the position of the eyes during anesthesia and sleep. Reported observations have been conflicting.1 During anesthesia different degrees of vergence have been noted, both vertical and horizontal, as well as roving motions during the induction. In surgical anesthesia the movements cease, and during the asphyxial stage a convergent depressed position may be assumed. A similar behavior may be noted during sleep.2It is frequently observed that esotropia disappears during anesthesia, with straight eyes or divergence taking its place. This finding differentiates a purely innervational from an anatomic or mechanical strabismus and may trap the uninitiated into minimizing the necessary surgery.Electromyography casts light upon the peculiar innervation during anesthesia and sleep. Operative procedures were carried out in a shielded room. The electromyographic technique has been previously reported.3 Electro-oculography also was carried out with use of capacitance-coupled preamplifiers with a time constant of 0.5

The question of extraocular muscle proprioception * has been labored long and vehemently in ophthalmologic literature. The existence of muscle sense, that is, a knowledge of the position of the eyes due to messages from the ocular muscles, strongly advocated by Sherrington,1 has now been generally denied. The information derived from vision and the innervational urge are said to be adequate to explain our awareness or lack of awareness of eye position.2,3 That the extraocular muscles should lack a mechanism for the recording of muscle tension, however, would place them so far apart from other skeletal muscle as to arouse wonder and doubt that they should be so distinguished. The fact that the extraocular muscles do have anatomic and pharmacologic peculiarities has been long appreciated.The existence of unusual nerve endings in these muscles has been reported, and the occurrence of muscle spindles and other low-threshold stretch receptors has

Electromyography (EMG) of the extraocular muscles has afforded insight into innervational patterns of common and uncommon diseases affecting ocular motility. The method has been described previously.1,2 The following applications are of particular interest. A. NEUROGENIC PALSIES OF EXTRAOCULAR MUSCLES 1. Third, fourth, and sixth nerve palsies are frequently encountered in ophthalmological and neurological practice. It is of diagnostic and prognostic importance to establish the site and character of the lesion. Electromyography has an important role to play in such studies. The following observations considerably amplify the findings of Bjork.3 The presence of lower motor neuron denervation may be determined. The cardinal sign of denervation is fibrillation—the minute discharge of single muscle fiber potentials which occur spontaneously without relation to volition and indicate lower motor neuron damage. Characteristic fibrillations have been noted in oculomotor palsies.1 Caution is necessary in the interpretation of ocular muscle potentials, since small, single

The application of electrophysiologic techniques to the analysis of ocular motility problems has yielded important information and provided a most useful tool for diagnosis and research in related fields of ophthalmology and neurology.1-3Our understanding of normal patterns of innervation of the extraocular muscles has been advanced, and considerable insight has been obtained in the altered dynamics of ocular muscle pareses, myopathies, ptosis, myasthenia gravis, comitant strabismus, and nystagmus. The effect of drugs may be readily evaluated.The technique requires the subconjunctival insertion of fine-gauge concentric electrodes directly into the extraocular muscles, using only topical anesthesia. This is a simple, practical procedure, devoid of harmful effects—the only complication is the occasional occurrence of a subconjunctival ecchymosis which is a cosmetic blemish of brief duration. The muscle potentials are suitably amplified, displayed on dual beam oscilloscopes, and recorded with moving film photography. Extraocular muscle motor units have a duration of

THE FOLLOWING study on the treatment of glaucoma with the carbonic anhydrase inhibitor acetazoleamide ( 2-acetylamino-1,3,4-thiadiazole-5-sulfonamide; Diamox) was initiated in October, 1953, and covers a four-month period of observation.Inhibition of carbonic anhydrase by acetazoleamide is a new and useful means of lowering the intraocular pressure. Acetazoleamide, a heterocyclic sulfonamide, was developed by Roblin and associates, in 1950,* as a diuretic agent whose action was based on inhibition of carbonic anhydrase in the renal tubular epithelium. Carbonic anhydrase catalyzes the hydration of carbon dioxide to form carbonic acid: H2O+CO2⇄ H2CO3. The carbonic acid dissociates to form H+ and HCO3-. Thus, the level of hydrogen ions and bicarbonate ions is affected by this enzyme. In the kidney there ensues a hydrogen-sodium exchange between the tubular epithelium and the glomerular filtrate, resulting in the normal conservation of base and the formation of an acid urine.

IN THE Proctor Lecture of 1951, Duke-Elder1 described three main types of phasic variation of the intraocular tension in simple glaucoma. These were, first, the falling type of curve, occurring in 20% of cases, in which the tension was highest early in the morning; second, the rising type, occurring in 25% of cases, in which the tension was highest in the late afternoon, and, third, the double variation, or biphasic type, occurring in 55% of cases, in which there were two peaks, one in the forenoon and the other in the late afternoon. He noted that simple glaucoma was a state "characterized initially by an instability of the ocular tension which shows a diurnal phasic variation of more than 5.0 mm. Hg."Grant,2 in 1950, described his technique for tonography in detail and discussed its theory and application. As he stated, his work was based on the calculations

SCLEREDEMA adultorum, first described by Buschke1 (1900, 1902), is a rare systemic disease characterized by generalized nonpitting edema of the body unassociated with fever, loss of weight, or much evidence of illness. It is preceded by an acute infection, usually respiratory, and of streptococcal origin. There follows an asymptomatic period, varying from a few days to several months, although occasionally there may be a prodrome of malaise, myalgia, and low-grade fever. Then begins a pale, firm swelling of the skin, commencing as a rule at the nape of the neck and referred to by the patient as a "stiff neck." It spreads to the face, chest, trunk, and abdomen, and, to a less extent, the extremities. The evolution of edema is rapid, being sometimes a matter of only two or three weeks. A slow regression commences soon, which may take from one to eight months. Isolated patches or islands

An inverse relationship between accommodative convergence to accommodation (AC/A ratio) and the monocular amplitude of accommodative response was found in ten young patients with accommodative esotropia. Drugs which act on the ciliary muscle caused reciprocal changes in these two measures: a cycloplegic increased the AC/A with a decrease in amplitude, while a miotic lowered the AC/A and raised the amplitude. The suggestion is made that the magnitude of the AC/A in these cases may be determined by the efficiency of the peripheral accommodative mechanism. A high AC/A ratio would indicate a weakness of this mechanism. Thus, greater effort would be necessary to bring about a unit change in accommodation and more accommodative convergence is produced.

Periodic alternating gaze deviation is an involuntary, continuous (except during sleep), cyclic disorder of eye movements. A single cycle consists of a conjugate horizontal deviation of the eyes to one side for about two minutes, followed by a slow conjugate horizontal movement of the eyes to the opposite side, maintenance of the conjugate horizontal deviation to this latter side for about two minutes, and then slow conjugate horizontal movement of the eyes back to the original side.This phenomenon is rare. The only other patient reported was briefly described by Kestenbaum.5 "Both eyes were turned to the right in a conjugate deviation. After a certain time, both eyes wandered slowly to the left and stayed there in conjugate deviation to the left. Then the eyes returned to the right, etc. The periods of each deviation lasted from 1 to 2 minutes. The patient had a complete palsy of voluntary

INTRODUCTION Recent advances in energy amplification techniques have culminated in the development of a new light source, the laser (optical maser).1-3 The unusually intense, monochromatic beam which characterizes laser emission is of particular interest to the ophthalmologist and may find wide application in the biomedical sciences.4,5The present study describes the gross and microscopic appearance of ocular lesions produced by a pulsed ruby laser. Therapeutic photocoagulation, potential research applications, and personnel hazard are discussed. PRINCIPLES OF LASER EMISSION* The term laser is an achronym for /ight amplification by the stimulated emission of

FOR MANY years the existence of an angioma of the choroid has been consistently noted in the relatively few eyes examined histologically from cases of the Sturge-Weber syndrome. The features of this syndrome are well known and offer no diagnostic problems. In fully developed form, they are (1) nevus flammeus of the face, involving the cutaneous and conjunctival distribution of the trigeminal nerve; (2) glaucoma, of either infantile (buphthalmic) or adult type; (3) neurologic signs—Jacksonian epilepsy affecting the opposite half of the body, hemiplegia, dyspituitarism, and meningeal telangiectasia, which may be calcific.Less well known are the cases of choroidal angioma in which cutaneous stigmas are lacking and glaucoma may or may not be exhibited at the time of examination. Most of these tumors are found in eyes enucleated for absolute glaucoma (Lindenmeyer,1 1932; Hill and Dart,2 1936). Of particular interest and importance are the tumors which are

TERATOMAS have been the subject of innumerable scientific and philosophic speculations since the inception of oncology. Their bizarre disorganization of structure and their even more bizarre approach to organogenesis have long aroused great interest among pathologists and embryologists.Teratoma, literally a wondrous or monstrous growth, may be defined as a tumor containing tissues derived from two or more germ layers Most body tissues have been described in these tumors, and it has been said that the teratoma may well serve for a review of histology.1 Characteristically, however, gonadal tissues are hardly ever seen, and certain other tissues, such as liver, very rarely. Skin, bone, cartilage, connective tissue elements, epithelium of the respiratory and gastrointestinal tracts, smooth and striated muscle and glial and nerve tissues may all be present in abundance. These tissues may be mature or immature, the latter constituting the malignant, embryonal teratoma; but even the adult tissues

In the past few years there has been a great deal of interest in the recording of the action potentials of the extraocular muscles. This is a natural extension of the field of clinical electromyography, which has contributed so largely to understanding of the disturbances in nerve and muscle function throughout the body induced by trauma and disease. Studies of the human extraocular muscles were not attempted because of difficulties of technique and instrumentation. These obstacles have been overcome, and we now find ourselves on the threshold of a new understanding of many old problems common to ophthalmology and neurology; indeed, these disciplines are brought into even closer harmony. HISTORY High lights in the evolution of electrophysiologic concepts of nerve and muscle function are the following: 1. Dubois-Reymond, in 1848,1 established the "action current" principle, or wave of electrical negativity of the nerve impulse. 2. Piper,2 in 1907,

CHELATING agents (χηλ[unk], claw) are compounds which, by forming soluble complexes with specific metals or compounds, remove them from the chemical milieu in which they occur, thus extracting, or clawing, them out.This process can be demonstrated both in solutions and in tissues, affording us a useful tool in research and therapy. Grant1 (1952) reported on the use of the neutral sodium salt of ethylenediamine-tetraacetic acid, edathamil calcium-disodium (EDTA *) in the chelation of calcium from corneas exhibiting band keratopathy. Significant clearing was accomplished with 0.01 or 0.05 M. solutions applied in drop fashion for about 15 minutes to the previously deepithelized corneas. The calcific component of an opacity could be removed, but actual scarring, inflammatory infiltration, or vascularization was unaffected. The visual result, therefore, depended on the proportion of these components in the corneal lesion and upon any deeper alterations present in the eye.Band keratopathy is usually associated with

In a previous publication innervational aspects of convergence and divergence revealed by electromyography were described (Breinin and Moldaver,1 1955). It was shown that patients with intermittent exotropia experienced active innervation of the lateral rectus on diverging from the near point of convergence and at all times when the nonfixing eye deviated outward. This was true for all fixation distances.This report concerns additional data on the vergence mechanisms. In the cases of intermittent exotropia cited above, a remarkable finding in all instances was the fact that only the deviating eye showed increased innervation of the lateral rectus. The fixating eye showed no alteration of the innervation of either lateral or medial rectus. At first sight this suggested that the exo deviation was due to a monocular dissociation and that Hering's Law was invalid for this condition. If this were so, we should have to speak of an "abduction" rather

The fourth edition of Adler's Physiology of the Eye remains a tribute to the remarkable insight and industry of one man; it is also something of an anachronism. How rare it is, these days, to encounter a textbook based essentially upon the efforts of a single author—what a task it is to peruse, absorb, and distill the vast literature which has accumulated around the topics of ocular physiology! One has but to note the amazing proliferation of ophthalmic research journals during the past five years to recognize that our specialty is not isolated from the worldwide revolution in scientific communication. The subject matter of ocular physiology is not only to be found in the ophthalmic journals but to an everincreasing extent fills the pages of basic science journals in this country and abroad. It is obviously impossible for one man to digest the reams upon reams of facts and figures

TO THE EDITOR: —I have read Dr. Drohocki's letter with great interest. I certainly did not know of his work nor did our consulting engineers who are connected with major neurophysiological departments. Of course, integrating systems have been employed in electrophysiology for many years and in themselves are not unique. The particular combination of integrating and differentiating features in one instrument is I believe, unusual, although both principles have long been employed separately.Dr. Drohocki's first integrator was of the same type as ours, and certain of his criticisms are quite valid. It is tedious to measure amplitudes, but for certain purposes it supplies the best answer. The linearity, although not perfect, is adequate and is not altered by oscilloscope presentation (we do not use the inkwriter). As a matter of fact, the method upon which Dr. Drohocki finally settled, although most ingenious, would not suit the purpose of electromyography

In the article entitled "Chelation of Calcium with Edathamil Calcium-Disodium in Band Keratopathy and Corneal Calcium Affections," by Goodwin M. Breinin, M.D., and A. Gerard DeVoe, M.D. [December, 1954, issue, page 846], there appeared an error in nomenclature. Edathamil calcium-disodium was not the drug used in that study, but rather the authors used the disodium salt of ethylenediamine-tetraacetic acid, adjusted [to neutrality] with sodium bicarbonate.In the manuscript the term EDTA was used generically for the disodium salt of ethylenediamine-tetraacetic acid. This was regrettable, since it fostered confusion as to the substance used. In accordance with the A. M. A. policy of using [official or] Council-accepted nomenclature only, the manuscript editor unfortunately substituted the term edathamil calcium-disodium. This term actually refers to the end-product of calcium chelation, which would be quite ineffective as a treatment of such conditions.The exact nature of the chelating substance is complex and deserves future

This monograph in German is an up-to-date comprehensive review of the entire field of ocular electromyography. It includes an historical review of relevant material and carries the subject up to the present from the period of the monograph by Breinin, the papers by Papst and Esslen, and by Huber. The author discusses the anatomy and ultrastructure of extraocular muscle with a presentation of the problems implicit in the finding of slow and fast fibers in the extraocular muscle. There is a full discussion of technique and instrumentation, including the preparation of electromyographic needle electrodes, the quantitation of the electromyogram (EMG), and correlations of EMG with muscle biopsy specimens.The author reviews normal motility in terms of innervational aspects and extensively discusses the varieties of ocular motility disturbances. There is a rather extensive discussion of myopathy and an account of the findings in the retraction syndrome. Of interest is the observation