SJOGREN, (1938).-Acta. O0hthal., APPLICATIONS Cashell, the' · TREATMENTOFSEPTIC ULCEROFTHECORNEABY LOCALAPPLICATIONS OF PENICILLIN 313 The recognised treatments of septic ulcer are

312 FRANK JULER antd M. Y. YOUNQLONDE, S. and PELZ, M. D. (1933).-Jl. of Pediatrics, Vol. II, p. 594.MEYER, H. S. (1934).-Jl. of Pediatrics, Vol. IV, p. 218.PAYNE, R. T. (1933).-Lancet, Vol. I, p. 348.PAYNE, R. T. (1936).-.-Lancet, Vol. I, p. 655.PEARSON,'R. S. B. (1935).-Arch. Dis. Child'ren, Vol. X, p. 363.PEARSON, R. S. B. (1936).-Guy's Hosp. Reports, Vol. LXXXVI, p. 333.PYRAH, L. N. (1933).-.Brit. Ji. Surg., Vol. XX, p. 508.REMOUCHAMPS, E. (1906).-Semaine medicale, Paris, Vol. XXVI, p. 49.SHELDON, J. H. (19381939).-Proc. Roy. Soc. Med., Vol. XXXII, p. 255.SJOGREN, H. (1933).-Acta Ophthal., Supp. II,pp. 1-151.SJ6GREN, H. (1935).- Acta. Ophthal., Vol. XIII, pp. 1-45. The latter reference

includes a separate paper (pp. 40-45) on 'the histological changes in thenasal glands in cases of kerato-conjunctivitis sicca. 9

SJOGREN, H. (1938).-Acta. O0hthal., Vol. XVI, pp. 70-88. * 'ESJOGREN, H.-A new conception of Kerato-conjunctivitis Sicca. (Keratitis Fili-

formis in Hypofunction of the Lacrimal Glands). English translation fromthe monograph published in Sweden in 1933, by J. Bruce Hamilton,Australasian Publishing Co., Sydney, 1943.

SMITH, J. E. and BuMP, W. S. (1928) -Annals of Surgery, Vol. LXXXVIII, p. 91.STAHEL, W. (1938).-Klin. Wochenschrift., Vol. XVII, p. 1692, and Helvetica

Medica Acta, Vol. V, p. 579.STrEINITZ, F. (1929).-Monatsschr.f. Kinderheilk., Vol. XLII, p. 432.WEBER, F. P. (1923).-Brit. Ji. Derm. and Syph., Vol. XXXV, pp. 169-180.WEBER, F. P. (1933).-Proc. Roy. Soc. Med., Vol. XXVI, p. 526.WEBER, F. P, (1940).-Proc. Roy. Soc. Med., Vol. XXXIII, p. 329 (remarks).WEBER, F. P. and SCHLUTER, A. (1937).-A,-Deutch..Arch. Klin. Med., Vol. CLXXX,

PP. 333-340.

THE TREATMENT OF SEPTIC ULCER OF THECORNEA BY LOCAL APPLICATIONS

OF PENICILLIN*BY

FRANK JULER and M. Y. YOUNG, C.I.E.FROM THE PENICILLIN UNIT, ST. MARY'S HOSPITAL, PAISDINGTON

REPORTS from various sources have shown that the therapeuticresults of penicillin applications to the eye are beneficial andoccasionally dramatic.

Examples'are to be found in the papers on catarrhal ophthalmias(Milner, Cashell, Crawford and King), ophthalmia neonatorum(Sorsby and Hoffa) and in deep infections (Rycroft).

Septic ulcer of the cornea with or without hypopyon is a matterof considerable clinical severity, and it is a fact well known toophthalmologists of experience, that the prognosis with regard tothe' immediate cessation of the ulcerative process is a matterdepending not only upon the virulence of the infecting organism,but also in a marked degree upon the general condition of thepatient. The prognosis varies definitely with the age of the patient.In children ulcer with hypopyon responds well to ordinary routinetreatment, but in old broken-down persons the prognosis may bebad indeed.

Received for publication, May 11, 1945.

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TREATMENT OF SEPTIC ULCER OF THE CORNEA BYLOCAL APPLICATIONS OF PENICILLIN 313

The recognised treatments of septic ulcer are numerous andvaried, and it has been a source' of interest through a number ofyears to one of us (F.A.J.) to see the enthusiasm actorded to newforms of treatment, relegated in due course to the long list of " alsoran.A recent vaunted local treatment, sodium sulphacetamide, does

not appear to have convinced surgeons, in Southern England atany rate, of its outstanding value. It was therefore with hope thatclinical treatment with penicillin was started and this report is con,sidered by the authors to show that we have in this new remedy apowerful agent for good in this devastating disease.No attempt has been made in this series to evaluate the effect of

intramuscular penicillin; the product has been used by localmethods only;The number of ulcers treated to date is 23, two of which (No. 7)

occurred in the same eye with an interval of one month betweenthe attacks.We have ventured to assess the results as excellent in 14 cases,

good in five cases, poor in two cases and bad in two cases.The ages of those affected can be grouped as follows:Seven over 60 years old; of these, four did excellently and three

did well.Six between 50 and 60 years; one of these did badly (No. 1),

three did excellently, and two did poorly (Nos. 14 and 19).Seven were between -40 and 49 years; two did well, and five

excellently.One was aged 35 years and did not react to penicillin (No. 4,

Bac. Pyocyaneus).One was only 14 years of age, and reacted excellently.Method of use.-The routine treatment has been to instil two

drops of the solution on to the lower conjunctiva or if po'ssible onto the cornea itself. After some seconds the instillation is repeated.This programme is carried out hourly by day, and two hourly

by night until the condition is obv'iously under control, whenlonger.'intervals are permitted.

In addition, atropine sulphate is used three or fdur times daily,and a flap cover over the eye is attached to the forehead.The solution used- is of sodium penicillate in strength 500 units

to the c.c.: the drops are well to.lerated by the tissues.In a number of cases, with or without the previous application

of decicain, a few crystals. of the salt have been applied to the §ur-face of the corneal ulcer itself, the eyelids being held apart by thefingers for approximately a minute after the positioning of thecrystals. It was soon found that this application caused no unduereaction to the tissues of the cornea and conjunctiva, and that itcould be repeated.,at discretion with impunity. It some cases'thesub§sequent.pain was severe, necessitating rnor ia or a retrobulbars~~~~~~ecessitating.



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314 FRANK JULER and M. Y. YOUNG

injection of 4 per cent. procain. .It is suggested that impurity inthe drug is th5 cause of this pain.

Recently, it has been the practice to curette beneath the over-hanging edge the underlying infiltrated tissue with a small sharp,curette or spud, so that the subsequefit triturationor the crystallinesalt should enable the latter to attack the infection more vigorously.It is hoped that the severer types of case will respond more readilywith this method.With increasing experience, this metiod of attack, the rubbing

of the strong salt well into the severely infiltrated part of the cornea,is being made use of more frequently. It would seem only reason-able to expect that such a method would give the. best chance forthe drug to attack or stultify the infection, for the flow of lymphis from the periphery of the cornea, and toward the surface, whilstthe increase of tissue tension, even without increased intra-oculartension, must interfere with the diffusion of the salt into the infecteddeeper tissues.This method has also been found of service in disciform ker4titis,

the surface being scratched or abraded with a Graefe knife, and the- \ crystals rnubbed in.

A similar procedure in late infections occurring through trephineblebs has been hopeful in- its results. It would seem that a crystalallowed to dissolve on the surface of a trephine bleb exercises abeneficial effect onl an infection which has already reached theaqueous and even the vitreous.Bacteriology.-The bacteriology should be investigated both by

smear and by culture, from the ulcer itself and from the lower con-junctival fornix. It is important that the investigations should bemade but penicillin treatment should not be delayed until the cul-tures are developed. In these urgent cases penicillin treatmentshould be commenced immediately and if next day the culturesshow only insensitive organisms it can be- discontinued. Insen-sitive organisms are rare in the conjunctiva: the Bac. pyocyaneuswas the only one met with in the present series, and that only inone case. The others encountered were all sensitive: the list wasas follows:Pneumococcus in 5 cases.Staphylococcus aureus in 7 cases.Streptococcus in 5 cases.Morax-Axenfeld diplobacillus in 3 cases.Pneumobacillus in 2 cases.-Bac. Py0cyaneus in 1 case. -

An incident of interest was the frequent negative report of smearand/or culture. The use of fluorescein is sometimes responsible forthis, whilst previous treatment may at times clear the §urface orthe lacrimal lysozyine may have a surface effect.



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TREATMENT O SEPTIc_ULCER OF THE CRIEA BY-IILAL APPLICATIONS OF PENICILLIN 315

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TREATMENT OF SEPTIC ULCER OF THE CORNEA -BYLOCAL APPLICATIONS OF PENICILLIN 319

Clinical course.-In a few cases, especially of the less advancedtypes, the improvement has been dramatic, and in 12 to 14 hoursit may -be obvious. More frequently, however, especially inadvanced cases in ill nourished persons, it may be several days'before amelioration is obvious. Cases with much conjunctival dis-charge usually get rid of the latter in 24 to 48 hours.

' Cases with secondary glaucoma.-It is in these cases that delayin improvement is most marked, and it has been necessary to per-form Saeni'sch's section on account of spread of ulceration in -fiveeyes in addition to that with the non-sensitive (BR. Pyocyaneus)infection. In two of these penicillin solution was run into theanterior chamber without any harm to the interior of the eye, butit is doubtful if such a procedure is'worth while, for the hypopyonhas been found sterile on each occasion.Following the operation, there has been further spread of

ulceration in two cases (case 1, -in which the infection may wellhave been from a non-sensitive organism, and case 19).We have come to the conclusion that Saemisch section should

not be delayed in cases in which improvement is not materialisingand especially where the intra-ocular tension is raised, Rycroftendorses th'is view and points out the superiority of a Saemischsection over a sifnple paracentesis; we are in agreemerlt with this,but are not so happy as he is when he states that there is no riskof tfie formation of broad anterior synechiae. We feel sure, how-ever, that the benefits are outstanding, and suggest that theincision into the anterior chamber need not be a large one, althoughthe swollen infiltrated cornea, should be cut through over a widearea.

AddendumA note on the compatibility of penicillin--w[th the drugs used in

ophthalmology in solutions and ointments.Rycroft and Cameron have given interesting cultural results of

various substances which might be thought to modify the actionof penicillin and similar experiments have been carried out here,though not all of them with simila,r results. From the tests madewe can state that solutions of the following chemicals in commonuse in Ophthalmic therapy' do not interfere with the potency ofpenicillin 'by' tests in vitro t atropine sulphate, cocaine hydro-chloride, homatropine hydrobromf'ide, 'procaine and decicain.Fluorescein, however, in higher concentrations, inhibits penicillinto a small extent and might, perhaps, be avoided in immediate usewith penicillin.

Rycroft's'tests seem to indicate that'vaseline and adeps lanaeinterfere with the action of penicillin. We have not found this.Penicillin mixed with both of these substances retained its activityfor ten to twelve weeks in the refrigerator. At room temperature,



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FIG. 1.-Above (1) vaseline and penicillin (200 units) freshly made. Below (2)penicillin control (5 units).

FIG. 2.-Lanoline and pen' Penicillin control (5 units).

(200 units), t.wo months in refrigerator.I

I -



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TRBATMENT OF SEPTIC ULCER OF THE CORNEA 13YLOCAL A1PLICATIONS OF PENICILLIN S21'

FIG 3 Lanoline and penicilln (200 units), four months in refrigerator.Vase'line and penicillin (200 uis,two months at- room temperature.Peniicillin control (5,units).

however, the vaseline ointment wTas active for seven weeks but thelanoline ointment was inactive., Experiments suggest that.vaselineand lanoline vary in their action in accordance with their wa'tercontent.- With a completely anhydrous Ibase, penicillin fails to.diffuse, in vitro, but satisfactory resul-ts may be,obtained by theAddition, of 10-20 per cent. water to the base.

Lannette-wax cream. has occasionally been found ir'ritating to.very sensitive skinis but penicill-in-lanoline is fotally non-irritating.,The latter is too. hard for ready -use when removed,from- therefrigertator and is best prep'ared with arachis oil in the, proportionof three parts adeps-lantae to one part arachis oil.The photographs show the area. of inhibition of staphylococcus

ion agar plates around cups- in which penicillin preparations hadbeen placed. The darker areas around the cups 'represent the zonesof inhibition.



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322 ANNOTATION

SummaryThe result of treatment of septic ulcer of the cornea by local

applications of penicillin is reported in. twenty-three cases. Thecrystalline salt can. be applied to the ulcer itself without harm.

- Saemisch -section is advocated in serious cases. The results areconsidered favourable.

Acknowledgments.-Acknowledgment is made to the courtesyof. the Hon. Surgical staff at M.oorfields Eye Hospital for permis-sion for the transfer of cases for this research, and 'to the troubletaken by the house surgeons and almoners at the Hospital for thenecessary arrangQments..We also acknowledge with thafiks the assistance given by Dr.

C. H. Smith -in the laboratQry work, and to Mr. M. H. Payne onthe pharmaceutical side.

REFERENCESCASHELL, G. J. W. (1944).-Brit. Med. Jt,, Vol. I, p. 420,.MILNER,J. G. (194.4).-Brit. Med. Jl., Vol. II, p. 175..CRAWFORD, T. and KING. E. F. (1944).-BritJ1. Ophthal., Vol. XXVIII,.p. 373.SORSBY., A. a,nd HOFFA, E. (1945).-Brit. Med. JI., Vol. I, p. 114. -CAMERON cI94-.-Rrit. Med. Jl., Vol. I, p. 222.RYCROFT, B. W. (1945).-Brit. Ji. Ophthal., Vol. XXIX, P. 57.

ANNOTATION

The Ophthalmological Vineyard

In the -20th chapter of St. Matthew's gospel will be foutnd thewe:ll remembered parable of, the labourers in the vineyard. Forourselves we may acknowledge that we have always thought thatthose who were engaged first had cause for dissatisfaction when thelast comers received the same wage. All the emphasis seems to beon the side of the master. ' Friend, I do thee no wrong .... Isit not lawful for me to do what I will with my own?" We canunderstand the labourers viewing the matter in a different light,and those who had toiled all day b,eing indignant at the last comersbeing paid at the,same rates. It is not in human nature to workfor twelve hours for a penny or any other wage when you can getas much for only one hoir's work. Probably the 'parable containsmore than appears in this superficial view. What 'has this got -todo with ophthalmology ? The parable came into our mind -onreading letters on the subject of demobilisation from Army service.Those who have borne the burden and heat of the day, many ofwhom have been overseas for more than three years, will have alegitimate cause for grumbling if they are not returned to civil lifeas soon as possible after peace has been declared in Europe. If itis not possible to grant speedy release from Army service might it



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Documents

SJOGREN, (1938).-Acta. O0hthal., APPLICATIONS Cashell, the' · TREATMENTOFSEPTIC ULCEROFTHECORNEABY LOCALAPPLICATIONS OF PENICILLIN 313 The recognised treatments of septic ulcer are