Eye (1987) 1,441-465 Duke-Elder Lecture Retinal Arteritis, Retinal Vasculitis and Autoimmune Retinal Vasculitis M. D. SANDERS London I would like to thank the President and directorship of Professor Arnold Sorsby. This Council for honouring me with the task of Unit was subsequently transferred to St delivering the 4th Duke-Elder Lecture, and Thomas' with the Royal Eye Hospital in 1973. enabling me to pay tribute to one of the most Staffed by physicians, neurologists and oph­ distinguished British Ophthalmologists of this thalmologists, the Unit has provided a base century. for itensive in-patient investigation of compli­ Born near Dundee in 1898, Sir Stewart cated medical and neuro-ophthalmic prob­ Duke-Elder graduated from St Andrew's lems. Secondly, he was instrumental in this University with a BSc and special distinction author obtaining the Alexander Piggott in physiology. After medical training in Dun­ Warner Memorial Fellowship to study at the dee and Edinburgh he graduated, and like University of California, San Francisco, in many of his compatriots took the high road 1967-1968 under Professor W. F. Hoyt. south to London, where he was fortunate in On joining the staff of the Medical Eye Unit gaining the close friendship of one of at St Thomas' Hospital, it became clear to me London's most illustrious scientific ophthal­ that 'Retinal Vasculitis' was a major cause of mologists, Sir Herbert Parsons. His career visual morbidity and occurred particularly in progressed after appointments at Moorfields young people. In America, 10 per cent of Eye Hospital and St George's Hospital, to patients with severe visual handicap were attain the highest accolades available in his noted to have inflammatory eye disease.l In own land, and his international reputation many cases retinal changes occurred in the similarly grew as he received honours abroad. context of a systemic disease and the ocular His phenomenal ability to condense, con­ changes provided specific diagnostic clues to centrate and clarify, enabled him to write the the systemic disease. Retinal veins were pre­ greatest textbook of ophthalmology ever pro­ dominantly involved, although in some condi­ duced. His broad scientific scholarship tions the arteries appeared to bear the brunt enabled him to initiate and direct the Institute of the disease. Complex immunological of Ophthalmology in London, which he investigations were performed in addition to expanded to become an institute of world full ophthalmic examination so that the renown. natural history of the disease has been Sir Stewart had some influence on the observed over a period of 10 years. This paper nature of this lecture by two actions. In 1954 will therefore present clinical and immu­ he supported the establishment of a Medical nological information on 150 cases of retinal Eye Unit at the Royal Eye Hospital under the vasculitis seen at St Thomas' between 1975 From: National Hospital for Nervous Diseases and St Thomas' Hospital, London. Correspondence to: Mr. M. D. Sanders, FRCP, FRCS, Consultant Ophthalmologist, National Hospital for Nervous Diseases, Queen Square, London WCI. Presented at the Annual Congress of the Ophthalmological Society of the United Kingdom, April 1987. 442 M. D. SANDERS and 1985 which have been subdivided into later related to both arthritic and scrofular those with an associated systemic inflamma­ conditions.ll The advent of the ophthalmo­ tory disease and those with isolated 'Auto­ scope allowed advances in the diagnosis of immune Retinal Vasculitis'. All cases were retinal and choroidal conditions and deemed to have immune mediated vasculitis choroiditis became recognised.12 Combined and in all cases inflammatory causes were inflammation in the iris and choroid was actively excluded. The role of auto-immunity termed uveitis, which relates to the uvea· or has been established clinically and by the grape-like coat of the eye, due to its similarity development of an experimental animal to a black grape. Improved examination of the model which has enabled us to make immu­ eye by the slit lamp and indirect ophthalmo­ nological, neurophysiological, pathological scopy resulted in the recognition of peripheral and therapeutic observation. uveitis. Inflammation of the ciliary body has been Historical Aspects termed peripheral uveitis, 13 pars planitis14 and The concept of inflammationof the veins was more recently intermediate uveitis. firstestablished by another outstanding Scots­ Some revision of this classifiation now man in 1784, when John Hunter first pub­ seems appropriate with the realisation that lished a paper on 'Observations on the the retina contains many powerful antigens, Inflammation of the Internal Coats of the and may be more immunologically active than Veins'.2 Inflammation of the retinal vessels the uvea. The recent availability of monoclo­ was noted over 100 years later in pathological nal antibodies and the detection of retinal specimens by Parsons. 3 In 1890 a Birmingham antibodies should allow a more precise cate­ ophthalmologist, Henry Eales4 described 5 gorisation of ocular inflammatory disease. It cases of young men suffering from con­ does appear that retinal vasculitis emerges as stipation, epistaxis and associated retinal a distinct clinical entity though the primary haemorrhages. Though a high arterial tension immunological event may be directed against was described, in no patient was the sphyg­ constituents of the photoreceptor cells. The momanometer used. A tuberculous origin retina is presented to the immune system by was postulated by Axenfeld and Stock5 and it the retinal vessels and thus the predominant is probable that this was the cause of the con­ clinical and inflammatoryevents occur in rela­ dition Eales described though he obtained no tion to these vessels. Many of the conditions aetiological information in any of his cases. producing retinal disease have been pre­ The association of inflammatory changes in viously termed uveitis, though the author the retinal vessels with uveitis and systemic agrees with Maumenee15 who stated that diseases became well-recognised,6.7.s but a inflammation of the uvea as a primary event is strict nosological entity was not established. A rare and the term uveitis as generally applied form of central 'Retinal Vasculitis' was is inappropriate. described by Lyle and Wybar9 but evidence for an inflammatory basis has never been Vasculitis--The Clinical Spectrum established and Hart and otherslO considered Vasculitis is a clinico-pathological process this an haematological disorder, though characterised by inflammationand necrosis of extensive investigations have failed to elicit blood vessels. In some diseases vasculitis may the initiating cause. be a major feature, whereas in other diseases it occurs as a secondary phenomenon. Vessels Terminological Aspects of any size, and situated in any organ may be Confusion has persisted over the terminology involved. An association either direct or of inflammatory conditions of the eye. Many indirect can be established with immuno­ terms evolved on anatomical grounds without pathogenic mechanisms and immune com­ sufficient clinical, experimental pr path­ plexes mediation is being increasingly ological information being available. Iritis recognised as the underlying mechanism.16 was recognised by the ancients as an inflam­ The prevailing theory relates to primary or mation of the anterior portion of the eye and secondary deposition of immune complexes in DUKE-ELDER LECTURE 443 blood vessel walls, and elegant animal models titude of different causes. support these hypotheses.17 Similarly when the kidney is involved there Necrotising vasculitis was firstdescribed by is the potential for histological examination Kussmaul and Maier in 186618 in a 27 year old and evidence has accrued that DNA related man with classic periarteritis nodosa. antibodies have a predeliction for deposition Systemic vasculitis is recognised as an impor­ in the kidney. tant feature of several of the connective tissue Thus there is a wide spectrum of vasculitis or collagen vascular diseases such as rheu­ in the body, and the ophthalmologist must be matoid arthritis and detectable immune aware of some of these conditions in order to system abnormalities such as hypergam­ provide diagnostic advice. However, the reti­ maglobulinaemia, rheumatoid factor, nal vessels are unique in providing a substrate cryoglobulinaemia, circulating immune com­ in which a microcirculation may be studied plexes and hypocomplementaemia also testify with great precision. The ophthalmologist to an immunological aberration. therefore has a major role in clarifying the A relationship with viral induced disease nosological and diagnostic debate in patients such as hepatitis B, antigen-associated nec­ with vasculitis. rotising vasculitis, or to drug induced hyper­ The aim of this lecture is to concentrate the sensitivity reactions raises the question of attentions of ophthalmologists on the retina multiple triggering mechanisms. and the retinal vessels as being 'a priori' source of immunopathogenic activity and to Polyarteritis Classic escape from the conventional view that nodosa Allergic granulomatosis inflammatory ocular disease is labelled under Systemic necrotising the all encompassing blanket term 'uveitis'. Hypersensitivity Churg Strauss Syndrome Retinal vasculitis should be considered Vasculitis Henoch Schonlein when major inflammatory changes occur in purpura relation to the retinal vessels, often with Essential mixed accompanying