Norman Ashton

Role of Oxygen in the Genesis of Retrolental Fibroplasia: A Preliminary Report

IN view of the present controversy centring in the role of oxygen in the aetiology of retrolental fibroplasia, we have thought it essential to investigate the influence of varying concentrations of oxygen upon the immature retina. Since it is now well established that the earliest stages of this disease are angioblastic in nature and present as an overgrowth of the developing retinal vessels, it was necessary to select a laboratory animal in which the anatomy and embryology of the retinal vessels were comparable with those in man. In the cat, embryo vascular budding commences at the disc between the 35th and 45th day of intra-uterine life, but the vessels do not reach the retinal periphery until about 3 weeks after birth, whereas, in man, the retinal vasculature is complete at birth. The degree of retinal vascularization in the full-term kitten at birth and in the ensuing 3 weeks is therefore comparable in extent to that in the premature baby. Since, with minor variations, the retinal vascular development is in all other respects very similar to that in man, the kitten appeared to be ideal for our purpose. Our experiments have, therefore, been designed to investigate the immediate and remote effects of high, moderate, and low concentrations of oxygen upon the process of retinal vascularization during the first 3 weeks of the kittens life. Not all of these experiments have been completed and several others are now in progress, but the findings so far obtained appear to be sufficiently striking and significant to warrant a preliminary communication. Full experimental details and a discussion of the results will be given in a subsequent paper; this report will be confined to a description of the effect of high concentrations of oxygen upon growing retinal vessels, and the subsequent developments which follow the transfer of the animal to ordinary atmospheric conditions.

Retinal Vascularization in Health and Disease: Proctor Award Lecture of the Association for Research in Ophthalmology

It was my intention to speak today on the whole problem of new vessel formation in the eye, but owing to several new observations made in my department just before I left, which I would like to report to you, it will be necessary to confine my remarks to vessel growth in the retina.

Anatomical Study of Schlemm's Canal and Aqueous Veins by Means of Neoprene Casts Part I. Aqueous Veins

THE purpose of this paper is to report a new technique which has been devised to demonstrate the anatomy of Schlemms canal, its immediately related vessels and the aqueous veins in particular. It has long been recognized that an exact knowledge of the anatomy of Schlemms canal, apart from being of academic interest, is pre-requisite to the proper understanding of those physiological and pathological processes which are concerned with the elimination of intra-ocular fluids. Among the many important papers on the subject are those of Hovius (1716), Fontana (1781), Schlemm (1830), Retzius (1834), Rouget (1856), Schwalbe (1870), Leber (1873), Waldeyer (1875), Rochon-Duvigneaud (1892), Troncoso (1905), Henderson (1908), Maggiore (1917), Dvorak-Theobald (1934), Swindle (1937), and Kiss (1943). The work of most of these writers has been so well reviewed by Dvorak-Thepbald (1934) that there is no purpose to be served by re-capitulating it here. All their studies were made upon specimens injected with dyes or Indian ink, reconstructed serial sections, or combinations of the two methods. While the use of serial sections is a valuable technique in this type of investigation, it is one which has a number of serious disadvantages. It is exceedingly tedious and time-consuming, thus limiting the number of eyes which can be examined; furthermore, the specimen is distorted in varying degrees in the process of fixation and cutting, and models constructed from such preparations may, therefore, be most misleading. The present work began with an anatomical study of aqueous veins and, since there are no known histological characteristics by which they may be recognized in a section, it was decided to attempt to prepare Neoprene casts of Schlemms canal in eyes removed at operation in which aqueous veins had been previously identified and marked with a loop suture. Neoprene latex was first introduced for renal vascular studies by Lieb (1940), and has since been used by

PRIMARY TUMOURS OF THE IRIS

PRIMARY tumours of the iris have lately excited much attention and there are a number of interesting studies in the recent literature. Duke and Dunn (1958) carried out a pathological and follow-up examination of 43 iris tumours; Rones and Zimmerman (1958) studied a selected group of 38 melanotic, or potentially pigmented, neoplasms treated by iridectomy only; Cleasby (1958) followed up 21 cases of malignant melanomata of the iris; Reese and Cleasby (1959) analysed a series of 157 cases of malignant melanomata with special regard to treatment and prognosis, and Jensen (1963) reported upon a small series of ten such cases. A histological and follow-up study of cases of primary tumour of the iris from this Department is now reported, in which the analytical methods of the above workers have been closely followed in order to provide data as nearly comparable as possible. Some of the findings dealing with malignant melanomata were reported at the meeting of the European Ophthalmological Society in Vienna (Ashton and Wybar, 1964).

ANATOMICAL STUDIES OF THE TRABECULAR MESHWORK OF THE NORMAL HUMAN EYE

IN recent years increasing evidence has been obtained of an abnormal resistance to aqueous outflow in eyes affected with chronic simple glaucoma; it now appears essential to determine to what extent this may be attributable to structural changes and at which particular site or sites in the drainage area the impediment is located. In this problem, consideration of the trabecular meshwork is clearly of primary importance, but a true assessment of morbid anatomical changes and their distinction from appearances due to artefact can be based only upon an accurate knowledge of normal structure. Although many anatomical studies of the trabecular meshwork are available both in. papers and textbooks, they are frequently deficient in detail and differ from each other in important respects. As a preliminary to future work on pathological material, we have therefore thought it necessary to sununarize existing knowledge and to carry out, by old and new methods, a further anatomical study of this region.

Vascular changes in diabetes with particular reference to the retinal vessels; preliminary report.

Though no toxoplasma parasites have been discovered, and it is perhaps rather late to expect a positive finding, there can be no doubt concerning the diagnosis. The mothers negative serum-reaction is difficult to explain. It is conceivable that the child acquired the infection after birth, but this would appear highly improbable in view of the extremely early age at which the sight was thought to be abnormal, and the presence of developmental abnormalities such as gross persistence of pupillary membrane. The mother is now seven months pregnant. X-rays of the foetal skull show no abnormal calcification at present, but this next child will be examined for toxoplasmosis soon after birth. My thanks are due to Dr. J. A. Dudgeon for performing the serological tests, and to Dr. B. R. D. Wilson for information regarding the general condition of the patient. REFERENCES

Arteriolar involvement in diabetic retinopathy.

IN recent studies of diabetic retinopathy much emphasis has been placed upon the pathological changes on the venous side of the retinal circulation, and little attention has been directed towards the arterial involvement, which is now generally regarded as a late, super-added, non-specific development, attributable to arteriosclerotic or hypertensive mechanisms. In longstanding diabetes it is well recognized that arterioles throughout the body are particularly prone to undergo hyaline degeneration and occlusion; such changes are strikingly apparent, for example, in the small arteries of the pancreas and in the glomerular arterioles of the kidney. This arteriolar degeneration may be remarkably severe; indeed it has been stated that a substantial deposit of hyaline material in the arteriolar walls is characteristic of diabetes and is strong presumptive evidence of its existence when found histologically (Bell, 1946). Renal arteriosclerosis, for instance, is over three times as frequent in normotensive diabetics as in normotensive non-diabetics and the lesions are much more severe in the former (Bell, 1952). Our own experience in the histological study of extra-ocular tissues, removed post mortem from diabetic subjects, is completely in accord with this view. In an extensive investigation of the problem of diabetic retinopathy now being carried out at the Institute of Ophthalmology, a study has been made of the changes on the arterial side of the circulation. It has been found that in the later stages of diabetes, the retinal arterioles may be affected as severely as the extra-ocular arterioles, and that the arteriolar hyalinization and obliteration is responsible for a characteristic type of new channel formation within the retina and subsequently for the final and total destruction of the retinal capillary bed. It is probable, therefore, that this severe degree of arteriolar involvement should not be regarded merely as a super-added hypertensive complication, but as a characteristic, late development of the diabetic process itself. It is the purpose of this paper to report these findings, which have so far been only incompletely described (Ashton, 1951), and, as would now appear from the examination of more extensive material, in part erroneously interpreted.

Observations on the Choroidal Circulation

THE discovery of aqueous veins and subsequent studies of their significance in health and disease have been responsible in no small measure for a new impetus to research work in the aetiology of glaucoma, which in turn has necessitated a re-examination of our fundamental knowledge of the anatomy and physiology of the ocular circulation and the drainage of the aqueous humour, with particular reference to the ocular tension. Amid the abundant recent literature on these subjects are a few papers directing attention towards the minute anatomy of the choroidal circulation, and the findings reported would be of very great importance if the evidence could be regarded as conclusive. It is the purpose of this paper to discuss these reports in the light of our own experience, and to introduce a technique which is likely to prove of value in future work in this field. The anatomy of the small vessels in such a structure as the choroid cannot be studied adequately by the methods at present in use. It is impossible to reconstruct complicated minute branches and anastomoses from serial sections; dye injection preparations, while of much greater value, are not suitable for dissection and are, therefore, prone to misinterpretation. The earlier investigators, using an injection mass of vermillion and size, were much nearer to the ideal technique. In a previous publication, the value of Neoprene latex in the study of Schlemms canal and aqueous veins has already been demonstrated (Ashton, 1951, 1952) and we have now applied this technique to a study of the choroidal circulation. We are using Neoprene casts, together with flat sections and bulk preparations, to investigate the possible existence of arterio-venous anastomoses, with or without a glomus-like apparatus, in the choroidal circulation both in normal and pathological conditions.

EXPERIMENTAL OCCLUSION OF RETINAL ARTERIOLES (USING GRADED GLASS BALLOTINI)

DISEASE of the retinal vessels usually involves in varying degree the whole retinal vascular system, so that in considering the pathogenesis of any particular lesion it is often difficult to decide whether it is primarily related to the arterioles, capillaries, or venules. From the experimental point of view it would be of value if the sequelae of uncomplicated lesions in each part of the vascular tree could be separately studied. With this object in mind we have sought, as an initial step, a suitable material with which to occlude in vivo the retinal arterioles. The artificial emboli must, of course, be the appropriate size, and should be inert, easily identifiable, and simple to prepare, to inject, and to store. We have found that small glass balls or ballotini are eminently satisfactory for this purpose and, to make the method available to others pursuing similar lines of work, we report in this preliminary communication a description of our technique together with a brief survey of some of our findings.

Effect of Cortisone on Healing of Corneal Wounds

THE evidence that cortisone inhibits wound healing in animals and man through its depressant action upon fibroblastic activity has already been reviewed (Duke-Elder and Ashton, 1951), but this conclusion might not apply equally to repair-processes in the non-vascularized tissue of the cornea, in which the metabolism is peculiar and the structure unique. The following experiments were therefore designed to determine the effect of cortisone upon the healing of perforating wounds of the rabbit cornea.