ASEPTIC TECHNIQUE IN OPHTHALMOLOGY BY Henry F. Allen, M.D. ASEPTIC TECHNIQUE in hospital and office practice can be defined as a systematized, continuing effort to prevent infection by eliminating pathogenic micro-organisms from the patient's environment. As a form of preventive medicine it is inseparable from diagnostic procedure and therapeutic practice. It should be directed by the chief of service through his representative and should be supported by every member of the staff. It is of direct concern to the hospital administrator. It is above all a team effort, demanding the intelligent participation of all hospital and clinic personnel. The basis for aseptic procedure rests on fundamental concepts re- lating to the communicability, virulence, and destruction of microbes and the resistance or susceptibility of tissues. These foundations are firmly established in microbiology, epidemiology, and general surgery; specialized considerations determine their application to ophthalmo- logy. Bacteriologic fundamentals include such data as thermal death times of various groups and species of organisms, the relative steriliz- ing efficiency of moist and dry heat, and the ability of certain species to multiply in unpreserved solutions. Epidemiologic methods may reveal modes of transfer and vectors of disease. Surgical principles stress operating room procedure and discipline, hemostasis, and respect for tissues. When infections occur, violation of basic principles should always be suspected. XVhen claims for a new method or com- potund are at variance with existing knowledge of similar procedures and substances, acceptance should follow only after careful experi- mental and clinical evaluation of these claims. Whereas other tissues can usually deal successfully witlh smaller or larger numbers of pathogenic bacteria, the avascutlarity of the cornea, lens, and vitreous renders them especially vulnerable to attack bv pathogens and even by organisms which are relatively nonpathogenic for vascular structures. The latter, even though invaded, may emerge functionally unimpaired after elimination of infection by normal de- fense mechanisms with or without the help of specific therapy. But TR. AM. OPHTH. SOC., Vol. 57, 1959 t378 Henry F. Allen since transparency is synonymous with function in the cornea, lens, and vitreous, and since repair of damaged neural elements can occur to no significant degree in the retina, the development of an infectious process in the eye may lead to irreversible disability in spite of prompt and ultimately effective treatment. In intraocular infections there is literally no substitute for prevention. All ophthalmologists presumably wish to prevent infection and believe that they are taking all possible steps to do so. However, a large body of evidence shows the need for wider understanding of the principles and practices on which aseptic eye surgery must be based. This evidence consists of: (i) the continued occurrence of postopera- tive infections, both reported and unreported; (ii) breaks in technique apparent to the casual observer in many eye wards and clinics; (iii) ignorance on the part of many surgeons of basic safeguards against infection; and (iv) widespread use ofpreparations and devices, which, in spite of manufacturers' claims, not only are inefficient antiseptics, disinfectants, and sterilizers but may actually serve as vehicles of the very infections they are intended to prevent. Although much progress has been made, the constant threat of postoperative endophthalmitis can be minimized only by a systematic approach to the entire problem. In the absence of any other comprehensive treatment of the subject, these circumstances justify an outline of aseptic technique in ophthal- mology. With a view to the needs of ophthalmologists and others concerned with aseptic eye surgery, the following purposes were established: (1) To restate and summarize the principles of aseptic technique andhospitalhygiene ((2) To relatetheseprinciples to ophthalmicpractice and surgery (3) To present a systematic approach to prevention of eye infection with emphasis on methods ofprovedreliability (4) To point out the limitations and dangers of other methods (5) To evaluate certain devices and compounds in terms of their efficiency as sterilizers for practical use (6) To provide a ready reference source and bibliography of the subject (7) Toreportpreviously unpublished data from our laboratory (8) To suggest standards which may serve as a guide to hospitals wishing to strengthen their defences against infection Several excellent texts (1-4) cover the broad subjects of sterilization and prevention of infection in general surgery and other fields. It is Aveptic Technique in Ophlthalmiology 379 assumed that every ophtlhalmic surgeon has some familiarity with their contents and has received training in the fundamentals of operating room technique. To avoid repetition of material covered in these volumes, only basic principles will be reviewed. There will also be included material of importance to ophthalmologists which was omitted from such texts or has appeared since their publication. Data derived from surveys and experimental investigations carried out by our laboratory will be reported where pertinent. The primary emphasis will be upon etiology, epidemiology, and practical prophylaxis of ocular infections. Antibiotics may supplement but can never substitute for careful aseptic technique. In the brief history of these drugs, the development of bacterial resistance and of specific human hypersensitivity have refuted both their infallibility against organisms and their innocuous- ness to patients. The rise of antibiotic-resistant staphylococci and the existence of suchrefractory species as Proteus and Pseudomonas forbid complacency. It is unlikely that any antibiotic administered by any route can prevent infection resulting from irrigation of the anterior chamber with a pure culture of organisms in an aqueous solution. Anaphylactic deaths and other severe reactions make one consider the risk of sensitizing patients to future injections or of provoking a reaction in a previously sensitized patient. Before administering the antibiotics for prophylactic purposes, the surgeon must weigh their advantages against their hazards for each individual patient. The use of antibiotics in ophthalmology is a subject for a treatise in itself. As such, it falls largely outside the scope of this review. The greatest impediment to improvement in aseptic technique is the false sense of security generated in the minds of ophthalmic surgeons by the absence of infection from a series of intraocular operations. In some cases, this result must be attributed more to the fact that infec- tious agents do not readily establish themselves in the eye than to the perfection of the technique employed. As will be shown, only the busiest ophthalmic surgeons can cite a series large enough to have statistical significance. When postoperative infection strikes, it does so without warning. It may involve the eyes of several patients at once, and it usually destroys useful vision in the eyes it touches. For these reasons every avenue of exogenous infection must be considered and every means employed toblock these routes and to eliminate organisms at their source. Pitfalls commonly encountered in sterility testing are responsible for the majority of improbable or unsubstantiated claims by manufacturers 380 Heiii-y F. Allen and other proponents of products for sterilization. Such pitfalls include the use of starvation media for culturing test organisms, carryover of unneutralized bacteriostatic substances, failure to use resistant spores, and failure to incubate cultures long enough. The direct responsibility for aseptic technique, as for other aspects of patient care and protection, belongs to the physician who treats the patient. The surgeon who operates in ignorance of conditions and pro- cedures in his hospital cannot shift responsibility to higher authority or impute negligence to subordinate personnel. Personal responsibility carries both the right and the obligation to investigate and to correct or insist in writing upon correction of deficiencies. Rigid self-discipline must precede criticism of infractions on the part of others. In hospitals where ophthalmology is not a separate service, the ophthalmic chief must be prepared to educate the chief of surgery in the specific requirements of aseptic eye surgery. The hospital adminis- trator, the chief of the nursing service, and the hospital pharmacist must be oriented in the same direction. The initial institution of seemingly adequate precautions is not sufficient in itself. Many factors operate to inactivate or to infiltrate the barriers erected against bacteria. Periodic checks must, therefore, be carried out to ensure the continued effectiveness of current practices. Cultures of air, instruments, and supplies from the autoclave should be performed at regular intervals. The methods of conducting sterility surveys will be outlined below. Aseptic technique can be no stronger than its weakest component. An error on the part of any one of several individuals can break the chain of asepsis. The duty of the ophthalmologist is to educate, to organize, and to inspire with the desire for perfection the members of his team. Only when discipline becomes second nature and any break in tech- nique is detected instantly can it be said that the system is functioning as it should. Only by striving for the ideal of no infections can the incidence of infection be reduced to a minimum. THE DEVELOPMENT OF ANTISEPTIC AND ASEPTIC TECHNIQUE IN GENERAL AND OPHTHALMIIC SURGERY CONCEPTS OF INFECTION BEFORE 1850 The history of aseptic technique began with the discovery of micro- organisms and ofmethods for their destruction. Before the modern era, the value of dry heat (stoving) for rendering innocuous the fomites of scarlatina and smallpox was demonstrated by William Henry (5) in Aseptic Techniqcue in Ophthalmiiology 381 1831. It remained for Koch and WVolfhuegel (6) fifty years later to work out thermal death times of anhydrous spores. Their results have full validity today. A device designed by a French physicist in 1679 and known as "Papin's Digester" was the precursor of the modern auto- clave. Pasteur employed steam under pressure at 120° C. for steriliza- tion (1). Redard (7) demonstrated that this was an effective means of killing spores. During the first half of the nineteenth century, postoperative sup- puration and methods for its prevention received but scant mention in the ophthalmic literature. Infection was considered to be endogenous and therefore unavoidable in a certain percentage of cases. Travers (1825) believed that the degree of inflammation following cataract extraction depended upon "bodily habit" (8). He recommended cupping, purging, and an abstemious life, but his treatise contains no reference to cleanliness or to the care of instruments. OPHTHALMIC SURGERY IN THE PRE-ANTISEPTIC ERA, 1850-1875 The invention of the ophthalmoscope by Von Helmholtz at mid- century marked the beginning of modern ophthalmology. A few years later, the techniques of Albrecht von Graefe gave to intraocular surgery its first major advance since the introduction of cataract extraction through a corneal incision over one hundred years before. All of this preceded proof of the germ theory of disease by several years. The members of the First International Congress of Ophthal- mology, meeting at Brussels in 1857, could scarcely have dreamed that three years later Pasteur would awaken the world to the science of bacteriology with his Alemoire su1' la fernmenitation alcoolique. The rest of the third quarter-century would pass before Lister's contributions to antiseptic surgery would find their modified expression in the ophthalmic field. Describing conditions as they were in the pre-antiseptic period, Ernst Fuchs (9) noted that when he started as an aspirant at the clinic of the University of Vienna in 1873, Von Arlt "taught us to wipe Daviel's spoon between our lips before putting it into the eye, in order that it be moistened and made slippery." It is surprising that the inci- dence of cataract wound infection was only 8 to 10 percent under those circumstances. Following iridectomy, infections of the wound were exceptional. Fuchs attributed this difference to the role of free lens material in providing a good culture medium for bacteria. This it undoubtedly does. Kinoshita (10) has observed Pseudomonas con- tamination oflens homogenates at 4° C. t382 Henry 1'. Allen The following year Fuchs was sent on detached service to Billroth's general surgical clinic. By a stroke of good fortune, Lister himself came to demonstrate his methods to Billroth over a period of several weeks, and personally assisted Fuchs during his stay. When Fuchs returned in 1876 to become assistant in Von Arlt's clinic, he applied antiseptic techniques to preparation of the operative field and to sterilization of instruments and supplies. By this time others were beginning to follow the new trend and it was possible for the first time to visualize the beginning of the end of septic complications in intra- ocular surgery. THE ANTISEPTIC ERA, 1876-1886 The arrival ofthe new era was signalized in the ophthalmic literature in 1878 by Alfred Graefe's paper, "Antiseptic Wound-Treatment in Cataract Extraction" (11). Before his adoption of antiseptic measures, Graefe reported a minimum loss of 4 percent of eyes operated for cataract extraction, with an upper limit of 10 percent and an average loss of 5 to 6 percent. He succeeded in reducing these figures to the loss of two eyes in 114 consecutive operations by adoption of a modi- fied Listerian routine. The essential features of this were as follows: 1. Before operation the conjunietival sac was irrigated and the lids were l)athed with 2 percent carbolic acid. 2. Instruments were dipped in absolute alcohol (for an unspecified time). 3. Duriing operation, sponges freshly moistened in carbolic acid were used for swabbing the conjunctiva, sponging away aqueous and blood and cleansing the operative field. 4. At the end of operation, after removal of clots and coagula, the eye was meticulously cleansed with carbolized sponges. 5. In order to avoid contaminationi of the lids by airborne bacteria the enitire orbital regioni was immediately covered with closely applied Listerian boric lint (cotton impregnated with hot saturated boric acid solution and dried), which wvas theni covered with borated Eniglish oilcloth and padded with cottoin battinig before the final applicationi of a finie elastic flannel binocular bandage. 6. The operated eye was dressed daily for seven to eight days in the same mainner, keeping the lids closed and exposing them to the air for only the shortest interval betweeni carbolic bathing anid application of the boric dressings. 7. Atropine was instilled at the end of operation and once daily after the third day. Graefe's figures, both in regard to the pre-antiseptic incidence of intraocular infection and to reduction of this incidence by antiseptic Aseptic T'echnique in Ophthalmology38 a.38- techniques, were confirmed by a larger series reported by Horner three years later (12). Both Graefe and Fuchs mentioned specifically that the carbolic acid spray, used as ani integral part of the Listerian regime during operations elsewhere in the body, was too irritating to patient and surgeon to permit its use in ocular surgery. THE BEGINNINGS OFASEPSIS The decade 1880-90 saw many important milestones set along the road to surgical asepsis. The major advances may be tabuilated as follows (2): 1881 RobertKoch Destruction of spores by dry hot air GustavWolfhuegel 1882 RobertKoch Substituted bichloride of mercury for carbolic Ernst v. Bergmann acid Preoperative sterilization of instruments in bi- chloride Gustav Netuber Initroduced suirgical cap and gowin 1885 Curt Schimmelbuisch Live steam sterilization ofsurgical dressings 1888 Paul Redard First practical use of autoclatve for surgical sterilization' 1889 W. S. Halsted Combined asepsis with minimal trauma to tissues The last decade of the century saw two innovations which are now a permanent part of surgicaltechnique: 1896 Johannv. Mikulicz Introduced surgical mask 1898 Joseph Bloodgood Used sterile rubber gloves for aseptic ptur- poses0v In ophthalmology also, the trend changed from carbolic acid to bichloride of mercury. Millikin (1890) cites Landolt and Hirschberg as operators meticulous in their attention to details of asepsis and anti- sepsis (13). The former cleansed the lids and irrigated the conjunctival sac before and during operation with bichloride of mercury 1:5,000. The latter, with the Prussian passion for discipline, made every visitor wash his hands with soap, soak them in bichloride of mercury, and don *Pasteur had previously sterilized liquids by heating them to 1200C. tinder pressure. "0Halsted had previously used rubber gloves to protect the skin from bichloride of mercury. The history of the idea of wearing rubber gloves has recently been tracedbacktothe year 1834 (43). t384 Henry F. Allen a white robe before witnessing an operation. Hirschberg also subjected all his dressings, bandages, solutions, and instruments to high degrees of heat in containers specially made for the purpose. Like Landolt, he insisted on the most careful cleansing of the eye and the ocular adnexa before operation. Millikin noted that pain could be avoided by making up bichloride of mercury with 4 percent cocaine solution, but stated that hyperemic injection of the conjunctiva was considerable as a result ofthe irrigation. By the turn of the century, all the basic principles of asepsis as we know them today had been clearly set forth, and it can truly be said that few if any significant advances have been made since that time in this area. That infections have occurred and continue to occur can usually be explained by the failure to observe one or more of these principles. THEPROBLEM OF OCULARINFECTION ETIOLOGY OFOCULARINFECTIONS TYPES OF ETIOLOGIC AGENTS. The eye is susceptible to infection by most of the organisms which are pathogenic for other tissues of the body (14). These include many species of parasites, protozoa, fungi, bacteria, spirochetes, rickettsia, chlamydozoaceae, and true viruses. Although the diseases caused by these organisms are described in scattered reports and in textbooks of ophthalmology, there is need for a modern textbook ofinfectious diseases oftheeye. Certain organisms are pathogenic only in the eye, while others exert their pathogenic effects primarily upon ocular tissues. The agent of trachoma, C. trachomatis, has its natural reservoir in the human con- junctiva, cornea, and lacrimal passages. The diplobacilli of Morax- Axenfeld and of Petit, the Koch-Weeks bacillus (H. aegyptius), and the commonhaybacillus (B. subtilis) are species which are pathogenic chiefly by virtue oftheir effect upon the eye. Adenovirus types 8 and 7 have been identified in cases ofepidemic kerato-conjunctivitis (15, 56). Although the disease may be accompanied by fever, malaise, and regional adenopathy, the ocular manifestations overshadow all other signs and symptoms. Newcastle disease of fowls produces a follicular conjunctivitis in humans with mild systemic manifestations (57). The eye is involved in certain generalized virus diseases, especially measles. Other viruses, such as herpes simplex, zoster, mumps, and several of the adenoviruses may involve ocular tissues in addition to other structures ofthebody. Aseptic Technique in Ophthalmology 385 Amongprotozoan infections, identification of Toxoplasma gondii as a cause of chorioretinitis and scleritis constitutes one of the most sig- nificant contributions to the etiology of these inflammatory processes (16, 17). Recent reports (18, 19) point to an increasing incidence of ocular fungus infections. Ley (20) has shown that steroids and antibiotics may facilitate and aggravate experimental keratomycosis. We have observed ocular moniliasis in patients receiving broad-spectrum anti- biotics byprolonged topical instillation. ROUTES OF OCULAR INFECTION. The intraocular tissues are subject to infection as a result of (a) direct implantation of organisms, (b) inward extension of an external infection, and (c) invasion by blood- borne organisms. Accidental perforating trauma often leads to panoph- thalmitis caused by one of the spore-forming soil bacteria, either anaerobic (Cl. welchii) (21) oraerobic (B. subtilis). Bacterial infections which follow elective intraocular surgery are almost always caused by a member species of one of two groups of vegetative organisms. The gram-positive cocci are most often repre- sented by S. aureus, less often by pneumococci, and more rarely by hemolytic streptococci. Among the gram-negative rods, Ps. aeruginosa, the bacillus pyocyaneus, is the chiefoffender, followedbyA. aerogenes, Proteus sp. (22), and coliform bacilli (113). Although spore-forming organisms are seldom identified in postoperative infections, they are often found in operatingrooms and must always be taken into account. We have recently observed a mixed infection by Proteus and B. subtilis followingretinal detachmentsurgery. Postoperative intraocular fungus infections have been reported by several authors (25-27). Such infections may not be so rare as was formerly believed. Fine and Zimmerman (55) report 13 new cases of exogenous intraocular mycotic infection, of which nine followed intra- ocular surgery. In eight ofthese the operationwas a cataract extraction. The authors stress the characteristic latent period of days, weeks, or months between presumed introduction of the organism and develop- ment of the clinical picture of a plastic type of iridocyclitis with anterior endophthalmitis. In general, the globe is resistant to inward extension of external infection from the conjunctiva and orbital tissues. Trephine blebs and filtering cicatrices form an exception to this rule. Two species which apparently lack the power to invade the intact corneal epithelium but which produce severe ulceration after gaining entrance through a superficial break are the pneumococcus (D. pneumoniae) and the 386 Henry F. Allen pyocyaneus bacillus (Ps. aeruginosa). Anthrax of the lids apparently spares the globe inevery case (23). The ability to penetrate the unbroken conjunctiva is a property of M. tuberculosis, P. tularense, and species of leptothrix. Septicemicbacterial metastases to the eye often produce panophthal- mitis. This was formerly a common occurrence in streptococcal puer- peral septicemia, and not rare in pneumococcal meningitis and pneumonia. Lewis (24), reviewing the literature on meningococcal meningitis, found a 10 percent incidence of endophthalmitis. We have observed panophthalmitis in staphylococcal septicemia and embolism of the central retinal artery' in subacute bacterial endocarditis. In some cases of presumed bacterial endophthalmitis, the offending organism is never recovered. This failure may be due to inaccessibility of organisms within the eye, or to faulty culture techniques. Unless a blood culture is positive, a surgeon has no justification for attributing the cause of infection to endogenous sources. Even the recovery of a pathogenic organism by no means establishes its origin. By the time infection has developed, many of the possible sources of infection are no longer available for analysis. Since treatment is usually ineffective, the best hope lies in prevention of infection. The keys to prevention areanticipation andvigilance. EPIDEMIOLOGY OFOCULARINFECIIONS History records many mechanisms for transmission of ocular disease. These range from the use of urine as an eye wash to the role of insects in carrying bacteria from eye to eye. Mother-to-child transmission is observed prenatally in gonorrheal ophthalmia and inclusion blen- norrhea (29); postnatally, in herpes simplex and trachoma. Insect vectors are responsible for ocular filariasis and onchocerciasis. Swim- ming pools have been indicted in outbreaks of adenovirus infection (28); and inclusion blennorrhea of adults (34). Lymphogranuloma of theeye has been transmitted both venereally and as a laboratory infec- tion (30). Animal hosts have been identified in leptothricosis, cat- scratch disease, tularemia, and many others. Ingestion of infected meat may lead to trichinosis, of raw milk, to brucellosis and tubercu- losis. The most ironic methods of transfer are those mediated by medical personnel. Outbreaks of pyocyaneus infection from contaminated solutions and transmission of epidemic keratoconjunctivitis by infected tonometers, ophthalmoscopes, and unwashed fingers furnish the most common examples of iatrogenic spread of ocular disease. Ophthal-