B. Tengroth

EFFECTS OF LONG-TERM SYSTEMIC STEROIDS ON CATARACT FORMATION AND ON AQUEOUS HUMOUR DYNAMICS

The occurrence of posterior subcapsular cataracts in some patients with rheumatoid arthritis treated with corticosteroid hormones in high doses over a long period of time was reported by Black et al. 1960 (6). This paper was later followed by more detailed reports by the same authors ( 7 ) . Afterwards subsequent papers have appeared in the literature, with diverging opinions concerning the relationship between corticosteroid treatment and cataract. In a recent paper by Sundmark where 3 cases of subcapsular cataracts were found among 48 patients, the literature is reviewed (17 ) . One of the objections is that many of the patients in the previous reports suffered from rheumatoid arthritis, and such a generalized disease might in itself play a r81e for the development of a cataract. The problem of a possible relationship between the development of a cataract and the intake of corticosteroids over a long period of time is also of a great interest because it might throw some new light on the physiology of the lens. Observations in cases of senile cataract indicating a reduction in blood flow through the secretory part of the eye and in aqueous flow has been demonstrated (9, 13). Topical application of steroids was found to increase the rate of aqueous flow in human eyes and the normal variations in flow during day and night were reduced in patients without normal adrenocortical activity (10, 12, 14). Recently a marked elevation of the intraocular pressure and an increased outflow resistance following topical application of steroids were reported (2, 8). A group of patients on long-term systemic steroid therapy showed an increased applanation pressure and a decreased water provocative facility of out-

HISTOLOGICAL STUDIES OF ORBITAL TISSUES IN A CASE OF ENDOCRINE EXOPHTHALMOS BEFORE AND AFTER REMISSION.

From the observations made by Asboe-Hansen 8c Iversen (1951 & 1952), Ludwig Boas & Soffer (1951) and others we know that there are characteristic changes in all mesenchymal tissues in humans with an endocrine exophthalmos as well as in experimental animals with a TSH-induced exophthalmos. Changes in the retrobulbar tissue in patients with endocrine exophthalmos have been studied previously (see Wybar 1957), both with ordinary histologic methods (Falconer & Alexander 1951) or with differenit histochemical (Iversen & Asboe-Hansen 1952) and biochemical techniques (Ludwig, Boas & Soffer 1951) The changes reported consist of an inflammatory readion, an accumulation of water-binding mucopolysaccharides and an increase in the number of mast cells. In this way a mucoid edema develops in the tissues However, only biopsies taken during decompression operations or operations on the external eye-muscles have hitherto been available. In the present case ,there was a unique opportunity to remove a large part of the orbital tissues before and after clinical remission. This makes a comparison between humans with endocrine exophthalmos and thyroxine treated animals with an experimentally induced exophthalmos possible.

RETINAL LESIONS PRODUCED BY Q-SWITCHED LASERS

In an earlier study, I (Bergqvist et al. 1965), investigations were made of the laser irradiance levels at which retinal lesions start to appear in a rabbit eye. These minimal lesions were observed in an ophthalmoscope. The radiation sources were ruby and Nd-glass lasers. The study showed that the threshold irradiance levels (peak values) were of the same order of magnitude with all the lasers. The mean value of the retinal irradiance, covering Q-switched as well as normal ruby lasers (6943 A), was given as 170 MWcm-2. Studies of a corresponding nature have been made by Ham et al. (1965). They state threshold radiation doses which are considerably below those observed in study 1. In the case of a Q-switched laser one has a well defined radiation pulse and it should be possible to find the relation between the values given in study I and by Ham et al. (1965). For Q-switched ruby laser radiation the data in the latter paper correspond to a threshold retinal irradiance of 2.4 MWcm-2. The large discrepancies between the irradiance values found by Ham et al. and by us cannot be explained solely as a consequence of a difference in the definition of a minimal lesion or in the ophthalmoscopic technique. The experimental conditions differ in that, in study I, we used the direct laser beam, whereas Ham et al. irradiated the eye with a divergent beam. Subsequently the size of the retinal spot has been very small in study I and large, 0.8 mm, in the investigations by Ham et al. The choice of method of irradiating the eye is in general dependent on the

LASER ACTION ON THE HUMAN EYE.

Rather more than three years ago Maiman constructed the first laser or optical maser as it then was called. Since that time the device has undergone vast improvement and been used not only in scientific research, but also for military and industrial application. Lately possible medical uses of the laser have begun to be charted. Indeed, the laser beam will irresistibly revolutionize many aspects of science and technology. Up to the present the ruby laser has been the most common type. Its operating principle is that photons from a flash tube are pumped in to a ruby crystal in the form of a cylindrical rod with parallel and flat end surfaces which are coated with a reflecting substance, say silver, one end somewhat more thinly than the other. The light flashes excite chromium ions in the ruby crystal to a higher energy state. On returning to their normal state the chromium ions emit a red glow. If the proportion of exited ions exceeds a certain minimum, red light will be transmitted, almost wholly in axial direction so-called stimulated emission. One might say that a stream of photons are reflected to and fro in the crystal between its end surfaces, a process which constantly stimulates excited chromium ions to emit in step new photons in axial direction. The beam leaves the ruby rod from the end having the thinner reflecting coating and exhibits the following properties: it is a pencil of parallel rays, a coherent light of a definite wavelength and has extremely high intensity. Since the light pulse is parallel1 the illumination intensity does not diminish

ON THE OCCURRENCE AND NATURE OF EXOPHTHALMOGENIC SUBSTANCES, ESPECIALLY IN HUMAN SERUM

Biological factors capable of inducing an inflammatory reaction in connective tissue are known to exist. The mesenchymal reaction induced by these substances is characterized by a cellular infiltration and a mucoid edema. These changes, aptly described by the term mesenchymitis, lead to an increase in volume of the tissues afflicted. The pathogenetic substances are endogenously produced and they are perhaps involved in the hormonal control of connective tissue although their physiological role is unknown as yet. A disturbance in this control will give rise to disease and the most extensively studied disease characterized by the abovementioned changes is endocrine exophthalmos. The biochemical, histological and clinical picture of this disorder has recently been discussed elsewhere (Tengroth & F r i s h 1965). Although this mesenchymitis is for anatomical reasons most clearly manifested in the retrobulbar tissues and thus presents as exophthalmos, it is probably a systemic disorder. The active substances are widespread in action but nevertheless the descriptive term exophthalmogenic substances is convenient and will be used here. In the following, the nature of the exophthalmogenic substances and their occurrence in human serum in health and disease will be discussed. As the de-

THE TREATMENT OF RETINOBLASTOMAS WITH A 60CO APPLICATION

For more than six years a special 6OCo applicator has been used as a routine method for the treatment of patients with retinoblastoma. This applicator, which was described by Tengroth (1) and Rosengren and Tengroth (2), is a modification of that originally designed by Stallard (3). The device is in the form of a silver ring which can be sutured circumlimbal to the episclera. Attached to this ring is a malleable arm, the distal end of which is threaded to receive the platinum covered cobalt applicator. The size of the ring as well as the length of the arm can be chosen to fit the individual case (Figs. 1 a and 1 b). The radioactivity which in 1960 measured about 10 mCi has decreased to

RADIATION STUDIES ON THE RETINA

The study of radiation damage in different cell systems has been intensive during the last decade. Noel1 et al. (1954), Cibis et al. (1955) and Brown et al. (1955) have studied the radiation effects on the retina, with respect to electrophysiology, morphology and metabolism and have reported interesting data concerning an organ which together with the brain has been looked upon as radioresistant. The change in the ERG after x-radiation is of great interest, since it is a sensitive method that can be used repeatedly in patients. The possibility of following the ERG in patients treated with ionizing radiation would give the clinician an idea of the systemic effects. However, the nature of the ERG is still obscure, and it is not known exactly in which part or layer of the retina the different ERG components originate. As the cell elements in the retina differ from each other in radioresponsiveness, one could expect changes in ERG that would differ at different dose levels. In the investigations cited above a morphological technique was used for describing the changes in the single cells. Using a technique, by which small and reversible changes can be demonstrated, it should be possible to correlate small changes in ERG with small changes in the different cell elements and thus provide more detailed information concerning the nature of the ERG. The present investigation was performed in order to correlate the effects of irradiation on the ERG and the different cell elements in the retina. This part o f the study concerns the inner ganglion cells of the retina.

OXYGEN CONSUMPTION STUDIES ON GUINEA PIGS AFTER ADMINISTRATION OF D- AND L-THYROXINE. EFFECT ON THE WHOLE ANIMAL COMPARED WITH THAT ON ITS EYE MUSCLES.

Ever since it became possible to synthetize thyroxine, two optical isomers have been known, viz . Dand L-thyroxine (Harrington, 1928). The naturally OCcurring laevorotatory form possesses considerably greater biological activity than the dextrorotatory isomer (Gaddum, 1930), a fact verified by several workers (Pitt-Rivers and Lerman, 1948; Tabachnik et al., 1956; Starr, 1961). The activity of the two isomers has mainly been studied by estimations of their calorigenic effects, and great variations in the ratios of these effects have been reported. The discrepant results have been attributed to the difficulty of synthetizing non-racemic forms of the two thyroxine isomers. Unlike these estimations in vivo, some of which suggest that D-thyroxine has no biological activity whatsoever (Pitt-Rivers and Lerman, 1948) experiments in vitro have shown that the two isomers have similar effects upon mitochondria1 swelling (Shaw and Lennan, 1959; Tapley, 1959). From observations of how the two thyroxine isomers influence the oxygen consumption of various tissues (Tapley, 1959; Dunne and Tapley, 1960) it has been deduced that dissimilar distributions of the isomers in the organism could be responsible for the discrepant effects observed in vivo and in vitro. Thus

AN IMPROVED METHOD FOR THE ASSAY OF EXOPHTHALMOS‐PRODUCING SUBSTANCE**)

The experimental animal of choice for the assay of exophthalmos-producing substance has been the fish. While not all fish are responsive, Fzcndulus heteroclitus (Dobyns and Steelman, 1953), Fzcndulus parvippinis (Brunish, 1958), Cyprinus carpi0 p e r Kinderen, et al. 1960) and Carassius auratus (Nagata, 1960, Brunish et al. 1962 a) have been found suitable. In the present study, a fish closely related to the latter, namely, Carassius carassius, has been employed. The standard procedure for the quantification of exophthalmos has utilized the hand caliper to measure the intercorneal distance before and after injection of test substance. The technique of X-ray photography has been used to measure proptosis in guinea pigs (Tengroth, 1961) and in humans (Tengroth, 1962). Its application to the fish assay of EPS has been reported upon briefly (Brunish and Tengroth 196.3). It is the purpose of the present paper to describe this technique more fully, and to compare the results obtained with Carrassius carassius to those reported for Cyprinus carpio in the well-described bioassay of de Waard et al. (1962).

Electromyographic study of the eye muscles in endocrine exophthalmos.

Opinions diverge as to whether or not a single basic mechanism underlies the syndrome of endocrine exophthalmos (Rose, 1952; Lamberg, 1954; Falconer & Alexander, 1951 ; Mulvany, 1944; Cordes, 1954; Rundle, FinlayJones & Noad, 1953). According to Mulvany a distinction can be made between a thyrotoxic and a thyrotrophic type of exophthalmos. I t is possible, however, that combinations of these forms exist (Copper, 1948; Dayton, 1953). All except three of our 17 patients either acquired exophthalmos or had exacerbation of existing exophthalmos following various types of antithyroid therapy. Though, in the opinion of Mulvany, this type of exophthalmos should be classified as thyrotrophic, it seems more plausible to regard it as a mixed form. In the three exceptions exophthalmos developed spontaneously without previous signs of thyroid dysfunction or previous antithyroid therapy, but in those cases too, a thyroid-pituitary disorder was detected. Weakness of the extraocular muscles, or ophthalmoplegia, is known to be a common symptom of endocrine exophthalmos (Brain). Many different theories have been propounded to account for this phenomenon. Kappis (1910) suggested a neurogenic etiology, but the consensus today is that the eye-muscle changes are primary and located in the muscle tissue itself. Their nature, however, remains obscure. Brain attributed the ophthalmoplegia to increased tension within the muscle cone, but this view seems to be invalidated by the fact that in many cases ophthalmoplegia preceded the protrusion. The changes in the interstitial connective tissue, with an increase of the mucopolysaccharide content as well as metachromatic semilunar structures beneath the sarcolemma, as demonstrated by Asboe-Hansen, Iversen & Wichman (1952), could well account for the loss of muscle function. The effect of thyrotrophic hormone