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Up Front | Sep 2008

What is the Best Endophthalmitis Prophylaxis?

The jury is still out on this topic. CRST Europe invited cataract surgeons worldwide to comment on their preferred protocol.

The prevention of postoperative endophthalmitis has recently become a prominent issue among cataract surgeons because of the incrimination of leaky clear corneal incisions and the European Society of Cataract and Refractive Sugeons' (ESCRS) demonstration of an 80% reduction in endophthalmitis incidence with intracameral cefuroxime.1,2 Endophthalmitis is probably the most horrible complication of cataract surgery, and as a proponent of simultaneous bilateral cataract surgery (SBCS), I think nothing can strike greater fear in my heart than the prospect of bilateral simultaneous endophthalmitis.3 For the past 15 years, I have carefully studied antiinfective protocols. I have adopted the following protocol, which I feel is as good as any, and better than most.

Preoperatively, I administer four topical moxifloxacin drops, one drop every 10 minutes. I believe that fourth-generation fluoroquinolones are superior to older drugs in their spectrum of efficacy; they have lower frequencies of resistant strains. All patients also receive 5% povidone-iodine drops before entering the operating room, which has been demonstrated to reduce the risk of postoperative endophthalmitis.4 Povidine-iodine 10% is applied to the skin of the eyelids, nose, and forehead of the operative eye just before surgery.

I use diamond knives of my own design, as I strongly believe that cleaner, better sealing clear corneal incisions are one of the most important steps in endophthalmitis prevention. I fashion my incisions meticulously and keep them tight. Strict sterile separation of the right and left eyes is mandatory (Figure 1). Nothing travels from the right eye to the left, and we try to use balanced salt solution from different lots for the two eyes, and ophthalmic viscosurgical devices (OVDs; some carry a higher bioburden of 1/1,000 than other surgical supplies, 1/1,000,000) from different companies. The eye drape is changed after the first eye surgery, and the doctor and nurse(s) change their gloves before beginning the second eye. Additionally, continuity can be maintained by avoiding the changing of scrub nurses during a procedure; however, it is encouraged between left and right eyes.

I use intracameral moxifloxacin 100 µg in 0.1 cc balanced salt solution, injected via the sideport, as the final step of surgery. Injecting it into the capsular bag pressurizes the eye as the cannula is withdrawn.5 I used vancomycin in the past, but the generic vancomycin sold in Canada carries the risk of toxic anterior segment syndrome (TASS), and governments always buy generics. Cefuroxime has a narrower spectrum of efficacy than moxifloxacin, is more difficult to make up, carries the risk of allergy, and is a time-dependent drug, whereas moxifloxacin is dose dependent, assuring a much higher kill rate of methicillin-resistant Staphylococcus aureus in 3 hours.

I have used intracameral moxifloxacin in more than 2,500 eyes. I believe it to be the safest, most effective prophylactic agent.6 The 2007 American Society of Cataract and Refractive Surgery (ASCRS) member survey demonstrated strong preference for pre- and postoperative topical antibiotic prophylaxis, particularly fourth-generation topical fluoroquinolones, as opposed to intracameral antibiotics. Seventy-seven percent of respondents were not injecting intracameral antibiotics, citing possible risks including dilution errors, bacterial contamination and TASS. While most American surgeons do not report injecting intracameral antibiotics, 82% would do so if a reasonably priced commercial preparation were available.7 Europeans, however favor intracameral antibiotics, with cefuroxime being the favorite, undoubtedly due to the ESCRS' study and guidelines.8

I also emphasize and repeatedly reinforce the importance of postoperative antibiotics. I use moxifloxacin 0.5% (Vigamox; Alcon Laboratories, Inc. Fort Worth, Texas), prednisolone acetate 1% (Pred Forte; Allergan, Inc., Irvine, California) and ketorolac tromethamine 0.5% (Acular; Allergan, Inc.) drops six times daily for the first 3 days, followed by four times daily until all the bottles are empty. Different bottles are used for each eye, marked as such and taped together as right and left eye drops. Postoperative examination is performed on day 1, then between 7 and 12 days later, as determined by scheduling issues.

I have performed slightly in excess of 3,000 SBCS patients using the above protocol (except that I used vancomycin intracamerally before changing to moxifloxacin in October 2004). To date, I have had no endophthalmitis cases.

Scientifically sound studies of endophthalmitis prophylaxis are difficult to perform, mainly because the incidence of postoperative endophthalmitis is low, the medicolegal risks are high, and individual surgeons are reluctant to change their habits. To get any surgeon to stop using whatever prophylactic method he considers effective and study another method is difficult.

The only measures supported by scientific evidence are (1) preoperative povidone-iodine4 and (2) intracameral cefuroxime at the end of the surgery;2 however, this does not mean that other interventions do not prevent endophthalmitis. It is impossible to study every factor involved in cataract surgery, but we must use common sense and clinical judgment when deciding how to prevent endophthalmitis. A consensus protocol, like the one proposed in the guidelines set forth by the ESCRS,8 can be quite helpful.

It is probably more common than we would like to admit that the surgeon first meets the patient at the operating table. If he finds blepharitis or a prosthetic fellow eye, it is too late to take adequate prophylactic measures. For this reason, the surgeon or a well-trained assistant must identify and treat the risk factors for endophthalmitis before the day of surgery.

I do not routinely use preoperative topical antibiotics (theoretically, the bacterial load on the ocular surface is reduced; however, no study proves that topical antibiotics effectively prevent endophthalmitis). I prescribe a short course of fusidic acid and a lid scrub if the patient is atopic or has blepharitis.

For preoperative antisepsis, I use 5% povidone-iodine on the conjunctiva and periorbital skin, allowing it to act for at least 3 minutes. Although 3 minutes is a short time, in a busy operating theater it seems like a lifetime. Therefore, I tend to apply the povidone-iodine in an area outside the operating theater, such as a waiting area for patients. Before applying the povidone-iodine, a drop of local anesthetic is applied, and the patient is instructed to keep his eyes closed—thereby avoiding a dry corneal epithelium. The anesthetic should cut the stinging sensation brought on by the povidone-iodine. In cases of allergy or hyperthyroidism, I use 0.05% aqueous chlorhexidine instead of povidone-iodine.

Drapes should be properly placed, and due attention should be taken to make a well-designed watertight incision. When in doubt, I always place a stitch.

Driven by results of the Swedish9 and ESCRS2 endophthalmitis studies, I almost always use an intracameral injection of 1 mg of cefuroxime in 0.1 mL of normal saline solution at the end of the surgery. I believe vancomycin should not be used for prophylaxis; however, I would consider using it in patients allergic to cefuroxime.10 Moxifloxacin is could be an alternative; however, in Spain it is not available in the form of an eyedrop.

I never combine antibiotics with the irrigating solution, and I cannot understand why some colleagues favor this technique versus an intracameral injection of a controlled and exact dose at the end of surgery.

There is a lot of discussion whether to routinely use cefuroxime or moxifloxacin intracamerally. Accepting that we do not have an ideal antibiotic, I would rather use one supported by an ample experience in Sweden and by a randomized, controlled, prospective study (ie, cefuroxime)2,9 rather than one that has yet to prove its theoretical advantages11,12 (ie, vancomycin or moxifloxacin).

At the end of surgery, I always check the patient's wound and start a frequent topical antibiotic for approximately 1 week or until wound healing is secure. It is also important to warn the patient about postoperative signs and symptoms of infection that require a prompt check-up during the early postoperative weeks.

I start the patient with a fourth-generation fluoroquinolone (gatifloxacin [Zymar; Allergan, Inc.] or moxifloxacin [Vigamox]) four times daily, the day before surgery. This is continued for 1 week after surgery. The patient is asked to wash his face with soap and water the night before and the morning of surgery.

One drop of 2.5% povidone-iodine (10% diluted 1:4 with BSS Plus [Alcon Laboratories, Inc.]), is placed in the cul-de-sac and not washed out. A 4X4 soaked with 2.5% povidone-iodine is placed on the patient's closed eyelids for 10 minutes before surgery. No additional prep is done. We found that 5% povidone-iodine caused punctate keratitis; 2.5% causes less.

At the end of surgery, I hydrate the incisions (using the Wong hydration technique for both sideport and main incision) with vancomycin 1 mg per 0.1 cc. The anterior chamber is also pressurized with this solution (approximately 0.5 cc, for a total of 5 mg).

Paying attention to seemingly small details is the key to preventing endophthalmitis. I believe there are four key components that can reduce the risk: (1) using neutralized povidone-iodine pre- and postoperatively, (2) creating a well-designed, tight-sealing incision architecture, such as the scleral-limbal-corneal (SLIC) incision (a wisp of white keeps the wound tight), (3) intraoperative filtering of irrigating solutions with antibiotic prophylaxis, and (4) measuring intraocular pressure (IOP) 15 to 45 minutes postoperatively.

First, povidone-iodine has always been an important part of my infection control regimen. It works quickly and lasts longer than broad-spectrum antibiotics.13-15 Mark G. Speaker, MD, PhD, of New York, found that bacteria from external sources around the eye are the most common source of endophthalmitis.4 Therefore, I pay particular attention to the conjunctiva. Undiluted povidone-iodine may produce toxic effects on the cornea; however, I have developed a protocol for neutralizing it: (1) draw up 36.6 cc of balanced saline solution, (2) draw up 2 cc povidone-iodine solution 10%, and (3) add 1.4 cc sodium bicarbonate 8.4%. The protocol for diluted povidone-iodine, along with several other solutions, may be found on our Web site: www.stlukeseye.com/professionals.

Using a neutralized solution, we have had a 90% reduction of complaints from secondary tear deficiency syndrome. We have had no new problems with tear deficiency syndrome after surgery and no evidence of toxic effects to the cornea.

Second, the surgeon must use an incisional architecture that seals tightly. If the incision does not seal well, endophthalmitis may result. I have found that a SLIC incision, starting in the sclera and passing through the limbus into the cornea, makes good engineering sense. This limbal incision starts just posterior to the limbus, catching a wisp of sclera to create a better seal and tight wound closure. The incision measures 2X2.7 mm. Ideally, the more square the incision, the better the seal.

Third, the irrigation solution is filtered through a 0.5-µm millipore filter. At the end of the case, an antibiotic is injected into the anterior chamber. This practice is a key element in antibiotic prophylaxis;16 although there has been much controversy about resistance, I believe it is a nonissue because the dose is approximately one-tenth of the therapeutic dose. We have used these controlled dosages intracamerally at the end of the procedure for more than 25 years. The solution is composed of the following medications in a 0.1-cc intraocular solution: (1) 33.3 µg vancomycin, (2) 20 µg ceftazidime, and (3) 99 µg dexamethasone.

Fourth, we check IOP in the early postoperative period. This simple procedure is one of the most important things we can do to prevent endophthalmitis. It is often overlooked because many operating rooms are arranged without access to tonometry. This early postoperative check can be crucial in detecting low IOP, which may allow the influx of bacteria into the eye and cause endophthalmitis. It is equally important to catch elevated IOP secondary to residual viscoelastic or overfilling of the anterior chamber at the end of surgery. Early detection is key in lowering the risk of endophthalmitis caused by hypotony and IOP spikes.

In conclusion, endophthalmitis is generally preventable. Following these four principles has substantially reduced the risk of endophthalmitis in my practice.

In addition to assessing the cataract during the preoperative workup, I determine whether the patient is at increased risk for endophthalmitis. If an existing clinical condition may increase the risk (eg, infectious blepharitis), I treat that condition before I proceed with the cataract operation.

Once the patient who is scheduled for cataract surgery arrives at our outpatient surgery unit, dilating drops are applied. A total of four drops of fourth-generation fluoroquinolone are administered to the eye, once every 15 minutes before surgery. Intraoperatively, a drape is used to isolate the eyelids and lashes after a topical antiseptic (ie, povidone-iodine) has been applied to the lids and cul-de-sac.

After cataract removal and IOL implantation, I ensure that the wound closure is watertight without stromal hydration. I typically use a temporal clear corneal incision. I always double check to be certain that the wound is watertight. If it is not, I place a suture. In these instances, one suture is usually sufficient to obtain watertightness.

At the conclusion of the procedure, the fourth-generation fluoroquinolone is used again, this time flooding the surface. Postoperatively, the patient is given the same fourth-generation fluoroquinolone to use four times daily for 10 to 14 days. My choice is moxifloxacin because of its superior penetration capabilities.

A big mistake we have seen in recent years is that surgeons have tried to save time in the operating room by not suturing wounds that are not watertight. Taking the time to suture adds minimal cost and time on the clock. Deviating from the surgical principle of a watertight wound at the conclusion our surgery is probably the biggest reason that we have seen an increase in postoperative endophthalmitis.

Despite improvements in surgical instrumentation and techniques leading to smaller incisions and shorter intraoperative times, the risk of endophthalmitis after cataract extraction remains a major concern. A substantial number of studies suggest an uptrend in the incidence of postoperative infection following the introduction of sutureless clear corneal surgery,17 while others suggest that rates have been fairly stable.

Well-designed prospective randomized clinical trials that address interventions for surgical prophylaxis are few and far between. With a relatively rare complication like endophthalmitis, the sample size (and associated costs) of such studies can truly be daunting. The vast majority of studies rely on the surrogate endpoint of cultures of aqueous taken at the conclusion of the procedure.

In the United States, preoperative povidone-iodine antisepsis is common, and the literature generally supports this intervention.4 The use of topical antibiotics pre- and postoperatively is also widespread; however, no antibiotics are approved for this use in ophthalmology, and the supportive evidence is weak.18

A number of European studies support the intraoperative injection of intracameral antibiotics. In the ESCRS study, intracameral cefuroxime was associated with a lower risk of infection;16 however, there was an apparently high rate of infection in eyes not treated with intracameral drug (3.4 cases per 1,000), and a much higher (almost sixfold) incidence of endophthalmitis in eyes with clear corneal incisions compared with scleral tunnels.2 To date, this strategy for prophylaxis has not been widely accepted into clinical practice.

One reservation regarding use of cefuroxime is the lack of a commercially available preparation. Therefore, surgeons must accept responsibility for the preparation of appropriate dilutions of drug and the risk of TASS that attends the use of such an intraocular solution. Additionally, concerns exist regarding statistical analysis because two different groups not receiving cefuroxime were combined and compared with two other groups that received cefuroxime.

Currently, evidence of efficacy for different strategies of prophylaxis is inconclusive. My personal belief is that rigorous adherence to a sterile technique, preoperative povidone-iodine antisepsis, and pre- and postoperative topical antibiotic therapy is reasonable. Careful attention to wound architecture is crucial, and if there is any doubt about the integrity of the wound, a suture should be placed at the end of surgery.19

My preference would be to see a second, well-designed clinical trial that would clearly resolve lingering uncertainty as to the value of intracameral antibiotics.

Attention to detail is everything in cataract surgery. I like to work in a cool theater. When the temperature creeps above 20°C, long operating lists become more tiring, and patients tend to sweat more—particularly if they are anxious—potentially releasing bacteria from the eyelid skin.

In common with most UK surgeons, I do not use topical antibiotic drops before surgery because there is no real evidence of their effectiveness. The pupil is dilated with cyclopentolate and phenylephrine. I carefully prep the eyelids, lashes, and brow using 10% povidone-iodine, making sure that it gets into the conjunctival sac. I then carefully dry the lids and lashes with two sponge swabs and drape the eye, making sure that the drape wraps around the lid margins and the lashes are out of the surgical field.

In my opinion, a quick and efficient surgical procedure is extremely important. My anesthesiologist used to say, "Quick surgery is not always good, but slow surgery is always bad." I think there is some truth in this; the shorter the operation, the less risk of unwanted events, such as infection.

I inject, rather than fold, the lens because it restricts contact with the ocular surface. For many years, I used vancomycin in the infusion fluid (10 mg/L). Although it may not be politically correct, it seemed to effectively prevent endophthalmitis. After our hospital took part in the ESCRS endophthalmitis study, however, we transitioned to intracameral cefuroxime (1 mg in 0.1 mL of normal saline solution).

Wound management is particularly important at the end of surgery, and no patient of mine leaves the table with a leaking wound. I hydrate the wound and then check that it is watertight with a dry sponge swab. If there is any doubt about the watertightness of the wound, I place a in a 10-0 Vicryl suture; however, this is rarely needed.

Postoperatively, my patients immediately start on tobramycin plus dexamethasone (Tobradex; Alcon Laboratories, Inc.) four times a day for 3 weeks. Touching wood, this protocol seems to work very well; I have not had a case of endophthalmitis for several years now.

The incidence of endophthalmitis after cataract surgery has appeared to increase over the past decade. Some studies show a greater incidence of postoperative endophthalmitis with clear corneal incisions than with scleral incisions, and a systematic literature review reported an uptrend in endophthalmitis rates after the inception of clear cornea wounds.20-22 The design, construction, and integrity of the clear corneal incision play a pivotal role in the reported increased rates of infection.23-25

A sound surgical technique can alter the risk of contamination of the anterior chamber with microbes. Poorly constructed and distorted wounds increase the likelihood of postoperative anterior chamber contamination. If the anterior chamber collapses and becomes shallow during surgery, it may also lead to contamination. One should adhere to closed-chamber technique principles, including a valvular incision and injection of an ophthalmic viscosurgical device before removing instruments from the eye, which averts fish-mouthing of the wound and distortion of the internal entry.

In routine phaco procedures, we make a paracentesis incision 2 to 3 clock-hours away from the site of the main incision. We use the soft shell viscosurgical technique to maintain a firm eye before creating the main incision. Sub-sequently, we make a temporal single-plane clear corneal incision in a single motion; the internal entry is approximately 1.5 mm long (Figure 2). If the incision is too short, the wound may be susceptible to postoperative perturbation and wound abnormality.

We conducted experimental and clinical trials26-28 on incisional architecture and its effect on incisional integrity with different phacoemulsification techniques. In a rabbit study, a sleeveless phaco tip caused greater collagen damage to the incision than a sleeved tip26 (Figure 3).

We also compared ocular surface fluid ingress into the anterior chamber after cortex removal (time point one) and IOL implantation as well as stromal hydration (time point two) in microcoaxial, standard coaxial, and bimanual phacoemulsification. Using trypan blue as the quantifying tracer, we found that trypan blue ingress was statistically significantly higher in the bimanual group than the standard coaxial and microcoaxial groups at both time points. At time point two, there was no statistically significant difference between the standard coaxial and microcoaxial groups.27

Several methods have been suggested to ensure proper sealing of the incision at the end of surgery. Currently, many surgeons use stromal hydration to enhance wound sealing and preclude the need for sutures. We prefer sealing the two paracenteses by hydrating the stroma with BSS Plus using the tip of a 27-gauge cannula. The main incision is sealed with stromal hydration of the incision's sidewalls and opposing the roof and floor by gently irrigating BSS Plus into the stroma. Additional BSS Plus is injected at the internal ends of the lateral walls until the internal entry is sealed (Figure 4). Any incision suspected of incompetence, including sideport paracenteses, should be considered for suturing with 10-0 Vicryl or nylon sutures. When we used trypan blue as a quantifiable ingress tracer, we found that stromal hydration of clear corneal incisions reduced ingress into the anterior chamber of trypan blue instilled on the ocular surface at the end of phacoemulsification.29

All surgeons should perform meticulous surgery with a well-controlled surgical technique using minimal intraoperative instrumentation. This will facilitate the maintenance of a well-formed anterior chamber throughout the operation. It is important to pay attention to incision distortion and resultant integrity at the conclusion of the surgery. Incision characteristics, such as ease of construction of the incision and the ability to self seal with high resistance to leakage, are preferred to reduce anterior chamber contamination and prevent endophthalmitis.

Steve A. Arshinoff, MD, FRCSC, practices with York Finch Eye Associates, Humber River Regional Hospital, and The University of Toronto, Ontario, Canada. Dr. Arshinoff states that he has no financial interest in the products or companies mentioned. He may be reached at tel: +1 416 745 6969; fax: +1 416 745 6724; e-mail: ifix2is@sympatico.ca.

Luis Cordovés, MD, is an Ophthalmic Surgeon at Servicio de Oftalmología, Hospital Universitario de Canarias, Tenerife, Spain. Dr. Cordovés states that he has no financial interest in the products or companies mentioned. He may be reached at e-mail: luis@cordoves.e.telefonica.net.

Luther L. Fry, MD, is Founder of Fry Eye Associates, Garden City, Kansas, and a Clinical Assistant Professor at the University of Kansas. Dr. Fry states that he has no financial interest in the products or companies mentioned. He may be reached at tel: +1 620 275 7248; fax: +1 620 275 5262; e-mail: lufry@fryeye.com.

James P. Gills, MD, is a Clinical Professor of Ophthalmology, University of South Florida, Consulting Professor, Duke University, and practices at St. Luke's Cataract & Laser Institute, Tarpon Springs, Florida. Dr. Gills states that he has no financial interest in the products or companies mentioned. He may be reached at tel: +1 727 938 2020; fax: +1 727 945 9481; e-mail: jgills@stlukeseye.com.

James McCulley, MD, is Professor and Chairman, Department of Ophthalmology, UT Southwestern Medical Center, Dallas. Dr. McCulley states that he is a consultant to Alcon Laboratories, Inc. He may be reached at e-mail: james.mcculley@utsouthwestern.edu.

Peter J. McDonnell, MD, is the William Holland Wilmer Professor and Director, The Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore. Dr. McDonnell states that he has no financial interest in the products or companies mentioned. He may be reached at tel: +1 443 287 1511; fax: +1 443 287 1514; e-mail: pmcdonn1@jhmi.edu.

David Spalton, FRCS, FRCP, FRCOphth, is a Consultant Ophthalmic Surgeon at St. Thomas' Hospital, London. Dr. Spalton is a member of the CRST Europe Editorial Board. He may be reached at spalton@eyepractice.fsnet.co.uk.

Abhay R. Vasavada, MS, FRCS, and Praveen R. Mamidipudi, DOMS, practice at the Iladevi Cataract & IOL Research Centre, Ahmedabad, India. Drs. Vasavada and Mamidipudi state that they have no financial interest in the products or companies mentioned. They may be reached at tel: +91 79 27492303 or +91 79 27490909; fax: +91 79 27411200; e-mail: icirc@abhayvasavada.com.