EDITORIAL THE SURGERY OF CORNEAL GRAFTS
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1 EDITORIAL THE SURGERY OF CORNEAL GRAFTS " The old never dies till this happen, till all the soul of the good that was in it get itself transformed into the practical new."--carlyle (I795-I88I). DURING the last twenty years there has been a steady expansion in the practice and progress of corneal graft surgery, brought about mainly by the influence of advances in associated branches of medicine and surgery as well as by quickened interest in international ophthalmology. Formerly, the achievement of a successful corneal graft was bedevilled by the constant presence of sepsis from which many eyes were lost, from the use of poor tools, inadequate anmsthesia, and no conception of the specific nature and reactions of tissue transplants. Nevertheless, for over a century, courageous attempts and failures continued to be recorded in spite of much disappointment, disheartenment, and widespread scepticism. " L'id6e de Reisinger qui consiste ~ remplacer la corn6e trouble d'un homme par la corn6e claire d'un animal est, certes, une fantaisie audacieuse et serait le plus grand succ& de la chirurgie si cette opdration r6ussissait " (Dieffenbach, 1831 ). However, the advent of the Listerian era at the end of the nineteenth century and the discovery of ether and chloroform paved the way for future successes which were exemplified by the case of Zirm in I9O6, who clearly proved that a successful corneal transplantation with subsequent improvement of vision was possible. At that time Zirm also enumerated his principles which hold good to this day, namely the avoidance of infection, the minimum of trauma and the maximum of protection to the graft, speedy technique, and the insistence that the graft must be obtained from the same species. To-day the conception of corneal transplantation within the same species is an accepted fact ; it is true that corneal grafts from different species may heal well, but such grafts never maintain transparency. Also, instruments of exquisite manufacture are now available from many countries, anaesthesia is no longer a problem, and infection has been well-nigh obliterated. So it is little wonder that corneal transplantation has become an established procedure in ophthalmic surgery and has enabled sight to be restored to many people who were blind from corneal disease and for whom otherwise, but for this operation, there was no hope. Problems still remain, however, to be solved: they are largely concerned with adequate supplies of sterile donor material and the correct interpretation of biological reactions which are common to grafts anywhere in the body. Surgical Technique.--The modern technique of corneal transplantation need not be discussed in detail. There are two types of graft in use: (I) Full thickness for deep corneal scars, comparable to a Wolfe graft (Figs. I and 2); (2) partial thickness for superficial scars, comparable to a Thiersch graft (Fig. 3). As in plastic surgery, firm fixation of the corneal graft is essential, and accurate adaptation of the edges of graft and host is of paramount importance for ultimate 17
2 EDITORIAL: THE SURGERY OF CORNEAL GRAFTS 171 transparency. Not only must the corneal graft heal but it must remain clear with little distortion of optical meridians. Methods of fixation vary from the use of multiple direct sutures with o.i mm. silk on 5 mm. needles to simple overlay FIG. I FIG. 2 Fig. I.--Keratitis profunda. Vision : hand movements. Fig. 2.--One month after operation ; 6 ram. full-thickness keratoplasty using donor graft stored twenty-three days at + 4 C. in liquid paraffin. After seven months the corrected vision of this eye was 6/6 and J. 2 (B. W. R.). (Case of Mr Campbell Shaw of Bournemouth). From B. W. Rycroft, " Corneal Grafts." Butterworth & Co. A FIG. 3 A, Initial state of an eye burned by molten metal. Male, aged 19 years. There was almost total symblepharon of upper and lower fornices which were treated by split-skin homoplasty. Two therapeutic lamellar corneal grafts were then carried out (G. J. Romanes) (from Brit. J. Ophthal. (I953), 37,239). B, The same eye two years later. Vision 6/36. From B. IV. Rycroft, " Corneal Grafts." B Butterworth & Co. sutures which pass over a disc of egg membrane covering the corneal graft underneath (Fig. 4). From various methods of technique it can be stated that all corneal grafts heal well ; about 8o per cent. acquire varying degrees of clarity, and about 5 per cent. of all cases of corneal blindness subjected to grafting obtain permanent improvement of vision in varying degrees.
3 172 BRITISH JOURNAL OF PLASTIC SURGERY FIG. 4 Stages in full-thickness trephine keratoplasty and direct suture fixation. From B. IV. Rycroft, " Corneal Grafts." Butterworth & Co. The Source of the Transplant.--(I) The ideal donor is the same patient, but whereas this source is generally possible in plastic surgery it is hardly ever available to the ophthalmic surgeon. However, cases have been reported and an example is shown (Figs. 5 and 6). This patient had a blind left eye but with a healthy cornea ; the right eye was blind in spite of previous attempts at lamellar keratoplasty on a dense corneal scar. A full-thickness corneal graft of 5 mm. was taken from the left cornea and transplanted to the right cornea. Vision in the right eye is now practically normal (6/9); the scar tissue was implanted in the left cornea to avoid the influence of any foreign transplant. (2) A second source of corneal graft material lies in the small number of
4 EDITORIAL: THE SURGERY OF CORNEAL GRAFTS I73 fresh eyes which have to be excised for intraocular growth or other involvement of the posterior half of the eyeball. With the advent of radium therapy and light coagulation fewer eyes are being excised for neoplasm, and this source is quite inadequate for the amount of corneal material required to-day. Fie. 5 Corneal autoplasty. Male, aged 56 years. Right eye: keratitis disciformis and previous lamellar keratoplasty. Left eye: normal cornea ; old optic atrophy. No perception of light. From B. W. Ryeroft, " Corneal Grafts." Butterworth & Co. FIG. 6 Five miuimetre full-thickness keratoplasty in the right eye with donor graft taken from the left eye. Placement of scar disc from the right eye in the left cornea to avoid immunological reaction (B. W.R.). (Case of Dr S. S. Sumner of Preston.) From B. W. Rycroft, " Corneal Grafts." Butterworth & Co. (3) Adequate supplies, therefore, can be obtained only from cadavers, and the idea of this source originated with the work of Filatov in I934 who showed that transparent corneal grafts could be obtained from the cadaver donor cornea. If the full value of this source is to be realised it follows that methods of preservation must be adequate. The use of inorganic material as donor material has varied from glass to
5 I74 BRITISH JOURNAL OF PLASTIC SURGERY plastic substances, but no permanent improvement of vision has yet been recorded, although the plastic implant has been retained for varying periods. The Donor Graft.--If the donor material is to be of value for an optical graft it must be excised within ten hours of death under aseptic precautions: it is only recently that the influence of potential infection from cadaver corneas has been realised. At the Regional Eye Bank at East Grinstead over 4o per cent. of all cadaver grafts have been found to be infected with pathogens, and these organisms are largely penicillin-resistant owing to previous penicillin therapy to the deceased. Therefore, it is essential that sterility of the material must be ensured before preservation, since preservation at low temperatures alone does not ensure sterility and is frequently the cause of spore formation. There are three main methods of preservation in use at the present time: (I) As a day-to-day measure in water vapour at 4 C. (refrigerator) ; (2) up to a FIG. 7 FIG. 8 Fig. 7.--The frozen eye is seen in the container immediately after removal from the deep=freeze bank where it has been for six months. Fig. 8.--After fifteen minutes at 37 C. The cornea and lens are clear. The air bubbles have run together and are seen just above centre. The eye is soft. From B. IV. Rycroft, " Corneal Grafts." Butterworth & Co. fortnight in liquid paraffin at 4 C. (refrigerator); (3) indefinitely at --79 C. (deep freeze). The preservation of a corneal graft in water vapour has been successfully employed for short periods, but it is of use only where there are large supplies of donor material. The liquid paraffin method of Burki is valuable and is the popular method of choice at the present day: it has been successfully employed at East Grinstead for nearly ten years. The deep-freeze method of preservation has not yet been entirely proven in the case of fuu-thickness grafts, but it is probable that this will be the method of the future. If successful, the adoption of this method will enable large quantities of grafts to be stored without wastage and will facilitate the orderly admission of patients to hospital. The technical principles are based on the work of Polge, Smith, and Parkes (1949) who showed that fowl sperm could be preserved for long periods at --79 C. after previous impregnation with 15 per cent. glycerol for sixty minutes. In applying these principles to corneal graft preservation, several criteria must be observed. The cells of the graft must remain viable and
6 EDITORIAL2 THE SURGERY OF CORNEAL GRAFTS I75 the graft must be sterile. Suitable material is first immersed in antibiotic solution for twenty minutes and then for one hour in 15 per cent. glycerol solution. Thereafter, the donor eye is dried, placed in a sterile vial which is immersed in CO2 snow contained within a large Dewar flask. When required for use the eye is rapidly thawed to 37 C. before use (Figs. 7 and 8). Preservation by freeze-drying or chemical means destroys the ceils and is unsuitable for corneal tissue though effective for bone or homostatic grafts. Successful clear grafts have been obtained after preservation for three weeks in liquid paraffin at 4 C. and after six months in the deep-freeze chamber. Biological Reactions.--The mass necrosis of a skin homotransplant after a few weeks, except in uniovular twins, is familiar to all plastic surgeons, but it does not occur in a corneal transplant and the question is often asked as to why a corneal graft behaves differently from the skin. Medawar believes that this is mainly due to the absence of blood-vessels, and others suggest that the low cell content of a small corneal disc offers a poor antigen dose. There is no doubt that corneal tissue can act as an antigen (Maumenee), but the stimulus must be smau and massive necrosis is never seen. Furthermore, in an animal previously immunised, skin will survive much longer when implanted into the avascular cornea than when into the abdominal wall, presumably due to the difference in the blood supply. The " second set phenomenon" is also common to skin and cornea, and it is well known that if skin from the donor of a corneal graft is implanted within four weeks into the rabbit which has had a successful corneal graft from the same animal, the corneal graft will go opaque but not if the second transplantation occurs beyond eight weeks or comes from another animal. This suggests that the cells of the original corneal graft have been largely replaced by host tissue, and one explanation is that a corneal graft survives mainly as a scaffold with the slow substitution of donor cells by the host over a period. This view is also supported by the steady clarification of a corneal graft which clinically is known to occur during several months after transplantation. Another view is that the original graft remains intact, since it is implanted in a position of privilege in avascular tissue. For the present it must be concluded that whether a corneal graft remains as a homovital or a homostatic graft is not yet proven. Causes of Failure.--There is no general standard of assessment on the success of a corneal graft, since some authorities claim that anatomical success should be the guide, whereas others insist that improvement of vision is the only real yardstick of success. The writer has always insisted that the measure of true success is a combination of these two points of view, since a clear corneal graft may not improve vision because of the presence of an unsuspected cataract, and a cloudy corneal graft with bad anatomical contour may often improve vision. The causes of failure may be summarised as follows :m I. Inadequate technique. The accurate alignment of the corneal graft and the host is essential for future transparency, and it is for this reason that very few successes have been reported in gross corneal burns where there was extensive fibroplasia and thickening of the host cornea with disparity of host and corneal donor tissue. Skill in manoeuvre and the use of fine instruments constantly contribute to improvement of technique.
7 I76 BRITISH JOURNAL OF PLASTIC SURGERY 2. The graft should abut on normal corneal tissue, since osmotic interplay can thereby improve vitality of the graft. The chances of survival where the graft is embedded in dense fibrous tissue are very poor but, per contra, when a graft is performed for conical cornea in healthy corneal tissue the results of success are about 9o per cent. 3. Neo-vascularisation is a frequent source of failure. This may be due to antigen reaction and subsequent fibroplasia of the graft-host relationship, or it may be due to inclusion of the iris in the corneal section carrying blood-vessels into the graft. Failure is practically never due to infection. 4. (Edema of the graft is an ill-understood phenomenon and may persist for months. It is not necessarily associated with vascularisation but tends to occur with prolonged preservation and poor donor material. 5. The selection of cases suitable for corneal grafting requires experience. A suitable eye should have had no recent vascularisation of the cornea and there must be a complete absence of glaucoma and retinal dysfunction, either from h~emorrhage or detachment. Cataract is not a contraindication, but in such cases the corneal graft must be carried out before extraction of the lens. After thermal or chemical burns it is not wise to attempt wide reconstruction of the conjunctival fornices before a corneal graft operation: the subsequent vascularisation, accentuated by operation, may prejudice the clarity of the graft and encourage invasion by new blood-vessels. Suitable cases for treatment by corneal graft surgery result from ulcers, deep keratitis, burns of all types, corneal wounds and injuries, corneal dystrophies, and corneal complications of the muco-cutaneous syndromes. Thus, it will be seen that many problems facing the pioneers of the nineteenth century have been resolved and the percentage of improved sight has risen from IO per cent. in I934 to over 60 per cent. in I954 (Paton). With the correct interpretation and further control of the biological reactions it may be confidently expected that this percentage of improvement will continue to rise. The future success of corneal graft surgery depends on the wise selection of cases, skilled technique, adequate donor supplies, and the evaluation of the antigen reactions and research into the influence of hormone derivatives. These problems are not the sole perquisite of ophthalmic surgeons for they concern all those who aspire to surgical success in this present era of transplantation. REFERENCES BURKI, E. (1947). v. Graefes Arch. OphthaL, xi4, 288. DIEFFENBACH, J. F. (1831). Z. Ophthal., I, 172. FILATOV, V. P. (1934). v. Graefes Arch. Ophthal., 4, 222. MAtrMENEE, A. E. (1951). Amer. ff. Ophthal., 34, 142. PATON, R. T. (1954). Arch. Ophthal., N.Y., 52, 871. POLGE, C., "SMITH, A. U., and PARKES, A. S. (1949)- Nature, Lond., x64, 666. ZIRM, E. (19o6). v. Graefes Arch. Ophthal., 64, 581. B. W. R.
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