ORTISONE IN OPHTHALMOLOGY
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130 ORTISONE IN OPHTHALMOLOGY By A. J. B. GOLDSMITH, F.R.C.S. and H. E. HOBBS, F.R.C.S. With its complexity of tissues and clear media through which the reactions of many of these tissues can be directly observed under considerable magnification, the eye is in many ways the ideal experimental organ in which to observe the effects of a powerful agent such as cortisone; it is not surprising, therefore, that since the introduction of this drug a considerable mass of experimental and clinical observation has accumulated from which generally accepted indications for, and methods of, treatment have been derived. In any consideration of the proper place of cor- tisone in ocular therapeutics, particularly when it is administered, as it generally is, by local applica- tion either by drops or by subconjunctival injec- tion, it is essential always to bear in mind its local clinical effects. These, in ocular disease may be summarized, in so far as is possible at the present time, by saying that it blocks temporarily the exudative phases of inflammation, whether bac- terial, allergic or traumatic in origin; that by inhibiting fibroblast formation in the process of repair it reduces the severity of, or in favourable circumstance may even prevent the damage and and scarring which may be catastrophic visually, inherent in the later processes of resolution, fibrosis and repair generally; while-most important of all from the long-term therapeutic point of view- it influences, in no way that one is aware of, the basic cause of the disease process. It has been confirmed by clinical experience that it is entirely without effect on the organized sequelae of organic disease, nor has it any effect on degenerative con- ditions except in so far as they, or some of them, may, during some period of their evolution, be associated with exudative phenomena. It follows from this very brief summary of its broad clinical effects that cortisone might be expected to be of greatest value in the treatment of certain acute inflammatory diseases of the eye, and in practice this has proved to be the case. In the management of such diseases it is fair to say that cortisone has provided the greatest advance in ocular therapeutics since the introduction of the various chemotherapeutic and antibiotic drugs now at our disposal. At first sight this statement may appear anomalous since it has been expressly stated that cortisone does not influence the funda- mental cause of the disease process, but two points must be borne in mind. The first is that many inflammatory diseases of the eye are self-limiting, either in their entirety or in their relapsing acute exacerbations; the second, that in the eye a very small area of scarring, which in practically every other tissue of the body would be without demon- strable effect on its economy and function, may have serious or disastrous results so far as vision is concerned, as, for example, corneal scars result- ing from various forms of keratitis, blocking up of the pupil by organization of the exudate poured out in a case of acute iritis and damage to the macular region of the retina by the oedema, or later by the scarring engendered by a disturbance in an adjacent region of the choroid. It is in the inhibition of such concomitants and sequelae of the acute inflammatory process that the great value of cortisone lies, so far as ocular diseases are con- cerned; but in using it, spectacular though its results may be, it is essential always to remember that in many of the conditions in which it is used the underlying causes of disease, the causes which may well be responsible for subsequent relapses, remain unaffected, and all possible steps must be taken to eliminate these if a cure in the real sense of the term is to be achieved. It cannot be too strongly emphasized that the making of a red eye white, gratifying though this may be, does not mean that everything necessary in the manage- ment of the case has been accomplished. Before discussing some conditions in which cortisone is of proven value its mode of administra- tion may be briefly reviewed. The effect of the drug upon the particular ocular lesion will, of of course, depend upon the local concentration achieved and, where this is in the superficial tissues-conjunctiva, episclera or superficial corneal layers-drops of a dilution of I :5 or i :Io of the standard suspension (2.5 or 5 mg. per ml.) are usually effective. As a maintenance dose they may be used two or'three times a day while in acute cases they may be given hourly. In acute inflam- mations of the anterior segment-iridocyclitis, copyright. on May 1, 2022 by guest. Protected by http://pmj.bmj.com/ Postgrad Med J: first published as 10.1136/pgmj.31.353.130 on 1 March 1955. Downloaded from
Transcript of ORTISONE IN OPHTHALMOLOGY
130
ORTISONE IN OPHTHALMOLOGYBy A. J. B. GOLDSMITH, F.R.C.S. and H. E. HOBBS, F.R.C.S.
With its complexity of tissues and clear mediathrough which the reactions of many of thesetissues can be directly observed under considerablemagnification, the eye is in many ways the idealexperimental organ in which to observe the effectsof a powerful agent such as cortisone; it is notsurprising, therefore, that since the introduction ofthis drug a considerable mass of experimental andclinical observation has accumulated from whichgenerally accepted indications for, and methods of,treatment have been derived.
In any consideration of the proper place of cor-tisone in ocular therapeutics, particularly when itis administered, as it generally is, by local applica-tion either by drops or by subconjunctival injec-tion, it is essential always to bear in mind its localclinical effects. These, in ocular disease may besummarized, in so far as is possible at the presenttime, by saying that it blocks temporarily theexudative phases of inflammation, whether bac-terial, allergic or traumatic in origin; that byinhibiting fibroblast formation in the process ofrepair it reduces the severity of, or in favourablecircumstance may even prevent the damage andand scarring which may be catastrophic visually,inherent in the later processes of resolution, fibrosisand repair generally; while-most important ofall from the long-term therapeutic point of view-it influences, in no way that one is aware of, thebasic cause of the disease process. It has beenconfirmed by clinical experience that it is entirelywithout effect on the organized sequelae of organicdisease, nor has it any effect on degenerative con-ditions except in so far as they, or some of them,may, during some period of their evolution, beassociated with exudative phenomena.
It follows from this very brief summary of itsbroad clinical effects that cortisone might beexpected to be of greatest value in the treatment ofcertain acute inflammatory diseases of the eye, andin practice this has proved to be the case. In themanagement of such diseases it is fair to say thatcortisone has provided the greatest advance inocular therapeutics since the introduction of thevarious chemotherapeutic and antibiotic drugs nowat our disposal. At first sight this statement may
appear anomalous since it has been expresslystated that cortisone does not influence the funda-mental cause of the disease process, but two pointsmust be borne in mind. The first is that manyinflammatory diseases of the eye are self-limiting,either in their entirety or in their relapsing acuteexacerbations; the second, that in the eye a verysmall area of scarring, which in practically everyother tissue of the body would be without demon-strable effect on its economy and function, mayhave serious or disastrous results so far as visionis concerned, as, for example, corneal scars result-ing from various forms of keratitis, blocking up ofthe pupil by organization of the exudate pouredout in a case of acute iritis and damage to themacular region of the retina by the oedema, orlater by the scarring engendered by a disturbancein an adjacent region of the choroid. It is in theinhibition of such concomitants and sequelae ofthe acute inflammatory process that the great valueof cortisone lies, so far as ocular diseases are con-cerned; but in using it, spectacular though itsresults may be, it is essential always to rememberthat in many of the conditions in which it is usedthe underlying causes of disease, the causes whichmay well be responsible for subsequent relapses,remain unaffected, and all possible steps must betaken to eliminate these if a cure in the real senseof the term is to be achieved. It cannot be toostrongly emphasized that the making of a red eyewhite, gratifying though this may be, does notmean that everything necessary in the manage-ment of the case has been accomplished.
Before discussing some conditions in whichcortisone is of proven value its mode of administra-tion may be briefly reviewed. The effect of thedrug upon the particular ocular lesion will, ofof course, depend upon the local concentrationachieved and, where this is in the superficialtissues-conjunctiva, episclera or superficial corneallayers-drops of a dilution of I :5 or i :Io of thestandard suspension (2.5 or 5 mg. per ml.) areusually effective. As a maintenance dose they maybe used two or'three times a day while in acutecases they may be given hourly. In acute inflam-mations of the anterior segment-iridocyclitis,
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March I955 GOLDSMITH AND HOBBS: Cortisone in Ophthalmolog 131
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FIG. i.-Syphilitis interstitial keratitis. Local cortisone treatment at onset of the attack.Eventual visual acuity 6/6. Faint corneal scars only.
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FIG. 2.-Syphilitis interstitial keratitis. In this case cortisone was started only after aperiod of systemic anti-syphilitic treatment and when the keratitis was in a floridstate. The end result is a dense central corneal scar and reduction of visual acuityto hand movements.
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132 POSTGRADUATE MEDICAL JOURNAL March I955
interstitial keratitis, etc.-o.25 ml. (6.25 mg.) ofthe standard suspension is often given by injectionunder the conjunctiva; whilst, if the posterior seg-ment of the globe is affected, the injection may bemade further back, into Tenon's capsule. Theinjections, which cause little or no reaction, maybe repeated every three or four days if necessaryor may be superseded by drops once the desiredeffect is achieved. Fortunately, in such cases, thedosage is so small that no risk of side effects needbe considered and no precautions in regard to suchneed be taken.
It is, of course, usual in cases treated withcortisone, however well they may be expected torespond, to continue with such other local treat-ment-atropine, antibiotics and the like-as maybe indicated, while as soon as possible steps shouldbe taken to investigate or, when known, to treatany systemic condition which may have a bearingon the local disease.
Certain conditions, to which brief reference willbe made later, are also treated by systemic cor-tisone and, of course, ACTH; in these the modeof administration, dosage and precautions followgeneral principles which need not be discussed;during such treatment, however, the eye should bekept under the most careful observation since itsresponse is not always that anticipated anddesired.Whether local or systemic administration is
used, a word of warning is called for in those casesdiagnosed as of tuberculous aetiology. In these,if the local reaction is allergic, proliferative andexudative, in nature, immediate benefit may wellaccrue; if, however, the local reaction is caseating(and the differentiation may well be clinicallyimpossible) the use of either cortisone or ACTHmay lead to an almost immediate deterioration inthe condition of the eye, an indication of coursefor the immediate cessation of these drugs and achange to the appropriate antibiotic therapy.
In the ensuing very brief discussion of illustra-tive specific ocular diseases in which cortisone isused more emphasis will be laid on those in whichit is of proven value than on the others in which itseffect is merely symptomatic or capricious. Ofthe former, the first to be mentioned is interstitialkeratitis. In its common form this is a manifesta-tion of congenital syphilis occurring usually inlate childhood or adolescence. Both eyes tend tobe affected, often with an interval which may be ofmonths or even years between the two, but it isunusual to have more than one attack in each eye.Systemic antisyphilitic treatment, if given duringthe course of an attack in one eye, has no influenceon its evolution; nor, given at this stage or earlier,does it diminish the liability of the second or ofboth eyes as the case may be, to be affected by
the disease. Clinically the affected eye is inflamed,red and painful, while there is a diffuse haze of thecornea which is soon followed by the growth intoit of superficial and deep blood vessels. Patho-logically there is, in the early stages, an inflam-matory oedema of the deep layers of the corneawith separation of the lamellae, a heavy leucocyticinfiltration and ingrowth of new vessels from thelimbal region. As the inflammatory process sub-sides, there is left more or less dense scarring ofthe deeper part of the cornea with permanentvascularization and opacity which is usually denseenough to interfere fairly seriously with clearvision, while the presence of blood vessels pre-judices the chances of a subsequent successfulkeratoplasty in that sooner or later the graft itselfmay become invaded by these vessels and becomeopaque.
In these cases, if cortisone is administered at anearly stage, the obvious signs of inflammation, thepain and redness of the eye disappear, the corneaclears remarkably rapidly, its neovascularization isinhibited or, if it has already started, ceases toprogress and the later sequelae of scarring andopacification are prevented. The comparison be-tween a case treated in the early stage with cor-tisone and one first treated only when the corneawas heavily vascularized, is well seen in theillustrations (Figs. i and 2). It is interesting thatalthough the response to cortisone may be quitedramatic and the eye may look almost normalwithin a few days, the use of the drug must becontinued for some six to eight weeks, which is thelength of time the attack would have persisted in amore or less florid form had its active manifesta-tions not been masked in this manner; if it isdiscontinued during this period the obviousdisease processes become reactivated. What pre-cisely is happening in the corneal tissues duringthis time to suppress their response to the noxiousfactor causing the inflammation is not known.From the fact that the other cornea may later beinvolved it would appear, however, that theprocess is a purely local one.The aetiology of many cases of acute iridocyclitis
remains speculative and even in those cases inwhich a definite association with diseases else-where, such as Still's disease, ankylosing spondy-litis and posterior urethritis, can clearly be demon-strated, treatment of the apparently primarycondition cannot with certainty prevent recurrentocular trouble. This, however, is no reason fornot taking such measures as may be possible toreduce the frequency and severity of the attackseven although the ravages of these may be com-pletely controlled. In iridocyclitis cortisone is ofmost value in those attacks associated with markedexudation, and in such its use even for a few days
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March 1955 GOLDSMITH AND HOBBS: Cortisone in Ophthalmology '33
only helps very greatly in controlling secondaryglaucoma, in preventing the formation of adhesionsof the iris to the lens and in the angle of theanterior chamber, and in preventing organizationof the exudate to form a membrane occluding thepupil and interfering thereby with vision. In themore chronic, granulomatous forms of iridocyclitis,in which plastic exudation is not a prominentfeature, cortisone is correspondingly of far lessvalue and is perhaps best used only to tide over atemporary crisis until other therapeutic measurescan begin to take effect. Somewhat similar con-siderations apply in cases of acute choroiditisaffecting the posterior part of the uveal tract,although the response of acute choroiditis to cor-tisone given either systemically or by orbitalinjection is capricious and is by no means asmarked, nor as satisfactory, as that of acuteinflammations of the anterior segment of the eye.The beneficial effects seen in iridocyclitis may
present dramatically in cases of sympatheticophthalmitis. In this condition, which typicallyfollows a perforating wound of the ciliary regionof one eye, a severe generalized inflammation ofthe. whole uveal tract (iris, ciliary body andchoroid) and retina develops, affecting not onlythe injured eye, but also the previously normal eyeand progresses only too frequently to disruptionof the whole ocular economy, shrinking of theeyes and complete blindness, the whole un-fortunate course being accompanied by severephysical pain as well as the mental stress obviouslyinvolved. The pathogenesis of the condition isstill obscure but it appears most likely on theevidence available to be primarily a virus infectionof the uveal tract, probably with a secondary de-velopment of allergy to uveal pigment which tendsto keep up activity once the primary virus infesta-tion has died out. The possibility of sympatheticophthalmitis has always been a grave anxiety tosurgeons dealing with wounds of the eye and withthese the generally accepted policy has always beento consider seriously excision of the eye, even whenpotentially useful, if the more active signs ofinflammation do not show marked and definiteevidence of subsiding within io to 14 days. Withthe advent of cortisone, however, this policy hasshown a change, and, provided that theinflammation responds to the use of cortisone andthat there is a reasonable chance of the injured eyebeing of value functionally or even only cosmetic-ally, most surgeons feel happier in making moreprolonged attempts to conserve the injured eyewithout feeling that they are running an unjustifi-able risk in regard to both. Fortunately, also,even in established cases of sympathetic ophthal-mitis, cortisone may be as useful as in interstitialkeratitis, although in the former disease its use may
have to be continued for as long as two years andwhen it is discontinued the eye must be watchedcarefully so that it can be resumed if necessary.There is no clinical indication as to when eyessuffering from this condition will be safe once theprotective influence of cortisone is withdrawn.As a corollary it will be obvious that cortisone
will be of equal value in such conditions as opera-tive wounds, in which, although the danger ofsympathetic ophthalmitis is not anticipated, theeye reacts unfavourably either inherently, throughthe trauma involved, or by the liberation of irritantmaterial such as soft lens matter. In these casescortisone in the small quantities used seems to havelittle or no prejudicial effect on wound healingand often helps to tide over the early post-operativeperiod and prevents more serious complicationsdeveloping such as, for example, the invasion of thegraft by blood vessels in an eye which has recentlybeen subjected to the operation of keratoplasty.
In many acute localized lesions of the cornea,sclera and conjunctiva cortisone has a valuable roleto play, provided always that adequate measuresare taken to determine the cause and treat it whereit is detectable. In infective conditions, providedthat the infection has been brought under con-trol, cortisone is unlikely adversely to affecthealing when employed topically in the usualamounts. Intractable conjunctivitis, spring catarrh,phlyctenular kerato-conjunctivitis, episcleritis androsacea keratitis are all conditions in which itsvalue appears to be chiefly in producing sympto-matic relief and administration may have to be pro-longed; in all of them it would seem justifiableto use cortisone in default or sometimes in anticipa-tion of response to other therapeutic measures; butin view of our ignorance of the effects-if any-ofreally prolonged administration, it would equallyseem advisable to take such other measures as maybe available to achieve permanent cure or evenonly quasi-permanent symptomatic relief.
Finally there may be mentioned certain con-ditions in the treatment of which systemic cortisoneorACTH appears to offer a more efficient means ofcontrolling the ocular manifestations of thedisease than has been hitherto available.
Opacification of the vitreous by the passage intoit of inflammatory exudates is an inconstant butgrave concomitant of uveitis, either as irido-cyclitis or as posterior uveitis, and the prognosis forultimate visual recovery when once dense vitreousopacities have formed becomes progressively worsethe longer their absorption is delayed. Cortisone,if it can reach the vitreous in adequate concentra-tion during the stage of active exudation, mayproduce rapid clearing of the vitreous and dramaticvisual improvement and in such cases the supple-
G1
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menting of intratenon injections by systemicACTH is valuable.
In cranial arteritis an ocular concomitant isblindness, usually bilateral, due to involvementnot of the central retinal artery but presumably ofthe small nutrient twigs supplying the optic nerveand usually occurring some little time after theother manifestations of pain in the face and headand tenderness of the temporal vessels. Immediatesymptomatic relief of the latter group of symptomsis usually given by systemic cortisone in smalldoses; it is not known in what proportion of casestreated or untreated by cortisone, blindness super-venes, but the symptomatic relief, and the pos-sibility that it may avert the ocular complicationmake its use eminently justifiable, especially asthere is no other known method of preventing thelesion of the optic nerve, nor of alleviating it andrestoring vision once it has developed.
Similar considerations apply in some of thedemyelinating lesions, particularly perhaps neuro-my:litis optica (Devic's disease), a comparativelyrare condition characterized ocularly by a bilateral
optic neuritis. This is of varying severity and it isimpossible to predict the outcome in terms of per-manent visual impairment. Systemic cortisone inthe early stages, however, often effects considerableimmediate visual improvement, but it is impossibleat the present time to say whether or not this isreflected in the eventual visual results.To summarize, cortisone cannot be said to cure
any ocular disease and its action is confined to thetime it is administered and shortly thereafter. Itsuse can in no way justifiably replace specificaetiological investigation and treatment, since inthe majority of the diseases in which it is used theultimate prognosis is dominated by the tendencyto relapses. Within this limitation its value is verygreat, particularly in acute cases and when thecause of the malady is eradicable, or the inflam-mation is self-limiting. There is no value, andevery possible danger, in its haphazard administra-tion in every chronic and recalcitrant diseaseaffecting the eye particularly if, in these cases, it isallowed to become a substitute for rational con-sideration, diagnosis, investigation and treatmentof the particular case.
CHEMOTHERAPEUTIC AND ANTIBIOTIC DRUGSReprinted from the Postgraduate Medical Journal
Price: 5s. the set, plus 3d. postageINTRODUCTION: THE PRINCIPLES OF CHEMOTHERAPY OF TROPICALCHEMOTHERAPY INFECTIONS OF THE BOWELC. A. Keele, M.D., F.R.C.P. A. R. D. Adams, M.D., F.R.C.P., D.TJM.
CHEMOTHERAPY OF NON-TUBERCULOUS CHEMOTHERAPY OF MALARIADISEASESOFTHECHEMOTHERAPY OF MALARIADISEASES OF THE CHESTHorace Joules, M.D., F.R.C.P. Prof. F. Murgatroyd, M.D., F.R.C.P., D.T.M.Horace Joules, M.D., F.R.C.P.
CHOEMOTHERAPY OF PULMONARY CHEMOTERAPY OF TUBERCULOUSTUBERCULOSIS IPNFECTIONS OF THE URINARY TRACTJ. G. Scadding, M.D., F.R.C.P. Arthur Jacobs, F.R.F.P.S.
CHEMOTHERAPY OF NON-PULMONARY CHEMOTHERAPY OF NON-TUBERCULOUSTUBERCULOUS CONDITIONS INFECTIONS OF THE URINARY TRACTPeter H. Buxton, M.R.C.P. F. R. Kilpatrick, M.S., F.R.C.S., and Kenneth
CHEMOTHERAPY AND THE VENEREAL Maclean, M.D., M.R.C.P.DISEASES MOST RECENT ANTIBIOTIC AGENTSR. R. Willcox, M.D. G. Brownlee, Ph.D., D.Sc.
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