BY RACHEL M. RENSHAW, EXECUTIVE EDITOR

TOP PHACO CONCERNS

Endophthalmitis Prophylaxis

Are Intracameral Antibiotics Really the Answer?

Since March 2006, surgeons have been debating and discussing the report issued by the European Society of Cataract and Refractive Surgeons (ESCRS) on the early findings from its endophthalmitis study. The ESCRS recommended that, based upon the report, surgeons use intracameral cefuroxime as the standard of care to prevent endophthalmitis in cataract procedures. This has not sat well with many surgeons in the United States for various reasons and led critics to ask several questions about the study, which was halted early due to overwhelming evidence of the superiority of intracameral cefuroxime.

Ophthalmology Management recently had the opportunity to speak with Randall J. Olson, M.D., professor and chair, Ophthalmology & Visual Sciences, University of Utah School of Medicine, and director of Moran Eye Center. Dr. Olson discusses the ESCRS study, the recommendations on intracameral cefuroxime and the ensuing debate at the 2007 meeting of the ESCRS in Stockholm, Sweden, in which he participated, along with Peter J. Barry, F.A.C.S., chairman of the ESCRS Endophthalmitis Study Group.

The Evidence for Intracameral Cefuroxime

Dr. Olson says the topic of intracameral cefuroxime has been percolating for some time now. There have been several studies from Sweden showing an advantage to intracameral cefuroxime, such as a recently published large nationwide prospective study by Lündstrom, et al.¹ They looked at the effects of incision type and location on endophthalmitis rates and found that the incidence of endophthalmitis increased dramatically when intracameral antibiotics were not used (P<.001).

The ESCRS study was a randomized, masked clinical trial that enrolled 16,000 patients and completed follow-up for more than 13,000 patients, an enormous undertaking and a commendable effort, says Dr. Olson. The investigators reported a fivefold increase in cases of postoperative endophthalmitis when intracameral cefuroxime was not used (odds ratio 4.59; 95% confidence interval, 1.74-12.08; P=.002).² On unmasking and first analysis, the study results were so compelling in favor of intracameral cefuroxime that the Data Monitoring Committee recommended that enrollment be halted. The results were published in the March 2006 issue of The Journal of Cataract and Refractive Surgery.

"While I have a difference of opinion, I have to say that this is the single best study on endophthalmitis in patients ever attempted in ophthalmology," Dr. Olson says. "In any study, especially one this large and ambitious, there's always room for people to pick at it. The question is this: Are there issues where we can come to agreement?"

The Control Group

Included in the criticisms that have arisen, mostly from U.S. surgeons, is that the control group was administered a topical fluoroquinolone once on the day of surgery, or starting the day after surgery. Dr. Olson says that he believes it would have been preferable to have studied a topical fluoroquinolone administered frequently the day of surgery.

"I think that Mr. Barry and I were in agreement that the ESCRS study could not answer the question of whether frequent topical drops are as effective as intracameral cefuroxime," says Dr. Olson.

"We [Moran Eye Center] performed a retrospective case cohort study where we showed that frequent antibiotic drops the day of surgery dramatically reduced the rates of endophthalmitis as opposed to waiting until the first postoperative day," Dr. Olson says. "In fact, our odds ratio were even greater [than the ESCRS study] and also very statistically significant."³

Dr. Olson is quick to point out that because the Moran Study to which he refers was retrospective, the quality of the data cannot match that of the ESCRS, but he says a randomized clinical trial would have to be launched to conclusively answer this question — an expensive and an ambitious undertaking.

"The second issue that was raised — and this is one that I think was unfair in hindsight — was that the rate of endophthalmitis, particularly in those patients who were getting no antibiotic at all, was unusually high, insinuating sloppy surgery," says Dr. Olson. "Fortunately we do have a follow-up study of Mr. Barry's study — the Swedish study by Lündstrom et al.¹ This is the largest registry of endophthalmitis and prospective cases ever performed in ophthalmology with over 250,000 patients registered. The overall incidence was less than 1 in 2,000, which, for a large study, is very respectable."

Dr. Olson says further that in the Swedish study, in the small group of patients in whom intracameral cefuroxime was not used because of allergy concerns, the incidence of endophthalmitis was highly statistically worse and not dissimilar from the incidence in Mr. Barry's control group.

The Cefuroxime Problem

The next issue that was raised regarding the study's implications to the worldwide community, says Dr. Olson, is that cefuroxime is not available in unit doses in the United States.

"In order to get widespread acceptance [of intracameral cefuroxime], especially in the litigious United States, you need something that people aren't mixing in the OR," Dr. Olson says. "It may be impossible to get a unit dose of cefuroxime because it appears that it never will be stable longer than a week or so. To use it, you'd basically have to have a hospital pharmacy make it. And what's the next concern stemming from that? Toxic anterior segment syndrome [TASS]."

Dr. Olson says that even in the ESCRS study, Mr. Barry reports that early on, some doctors formulated the cefuroxime incorrectly with sterile water instead of balanced salt solution and a mild form of TASS resulted.

"The anterior chamber is the least forgiving place for utilization of something intraocularly that exists in the body," he says. "The criteria and the standards that are set up for the Food and Drug Administration even for something that is intravenous, which is much more forgiving, are extremely strict with regard to criteria for particulates, pH and osmolarity, so when there is an approved unit dose for intraocular use, it's likely to be a fluoroquinolone, most likely of the fourth generation."

Dr. Olson says that surgeons should be cautious when considering topical fluoroquinolones for intraocular use. "The criteria for a topical drop vs. intravenous solution are vastly different in regard to purity, particulates and sterility — not even to mention that the bottles in which topical drops are packaged are not sterile," he says.

"I think a company ought to step up and go through the process of getting an approved intraocular fluoroquinolone that meets all those standards of purity that we would expect in something that we inject into the eye," says Dr. Olson.

Red Herring

According to Dr. Olson, another area of controversy arising from the findings of the ESCRS Endophthalmitis Study is that silicone IOLs were found to be associated with higher rates of endophthalmitis.²

"Mr. Barry has said that this was not the object of the study — surgeons could use any implant they wish, so it wasn't randomized," he says.

Techniques for Management of Floppy Iris Syndrome

By Uday Devgan, M.D. Intraoperative floppy iris syndrome (IFIS) was described by David Chang, M.D., in 2005 as a condition during cataract surgery associated with use of tamsulosin, (Flomax, Boehringer Ingelheim Pharmaceuticals, Inc.) an alpha blocker used in the treatment of prostate enlargement. Permanent changes to the iris tone can occur even after a short course of tamsulosin years prior to cataract surgery. The options for the management of IFIS are varied, from pharmacologic treatment to use of mechanical devices intra-operatively. The first sign of IFIS is often a poorly dilating pupil prior to the surgery. Upon making the first incision into the eye, excessive floppiness of the iris is apparent, as well as low iris tone and a tendency for the iris to prolapse out of the eye (Figure 1). Pharmacologic Treatment Preoperative mydriatic agents such as atropine (1% solution) can help to restore tone to the iris and achieve a sufficient level of dilation prior to the surgery. Robert Osher, M.D., has described the use of atropine 1% topically, twice a day for a few days before surgery.1 Sam Masket, M.D., has combined the preoperative atropine with intraoperative use of diluted epinephrine to further enhance the iris tone and level of pupillary dilation.2 Various strengths of epinephrine can be used, ranging from 1:4,000 to 1:20,000; however care should be taken to ensure that it is non-preserved, bisulfite-free epinephrine and the diluting agent should be balanced salt solution. Figure 1. Iris prolapse out of the corneal incision due to IFIS. Joel Shugar, M.D., has created a very effective mixture that he calls "epi-Shugarcaine" which is pH neutral agent that gives intracameral anesthesia as well as increased iris tone and pupillary dilation.3 This is created by mixing the following agents:4 ► 9 cc fortified balanced salt solution [BSS Plus, Alcon Laboratories] ► 4 cc bisulfite-free 1:1000 epinephrine [American Regent] ► 3 cc non-preserved lidocaine 4% [Hospira Inc.] This results in a final mixture which has a neutral pH of 7, 1:4000 epinephrine, and 0.75% lidocaine. A small amount, 0.25 to 0.5 cc, is placed into the anterior chamber at the beginning of the case. Note that since this is a non-preserved mixture, it should be refrigerated and any left over solution should be discarded at the end of the day or sooner if the solution takes on a reddish/brown color. Dr. Shugar and others have found the solution effective for nearly all cases of IFIS, particularly when supplemented with additional epi-Shugarcaine intraoperatively. Mechanical Devices To expand the pupil and prevent the iris from prolapsing, mechanical devices can be used to hold the iris. The most commonly used are iris hooks which are placed through additional incisions to retract the iris, typically at four points. There are other devices such as the Graether Pupil Expander (EagleVision Ophthalmics, Memphis, Tenn.) and the Perfect Pupil Expander (Milvella, Eden Prairie, Minn.). Of interest is a new device that is surprisingly simple, yet very effective, the Malyugin ring (MicroSurgical Technologies MST], Redmond, Wash. [Figure 2]), which retracts the iris and expands the pupil (Figure 3).

Figure 2. The Malyugin ring.

Figure 3:. Use of the Malyugin ring to dilate the pupil and retract the iris in cases of IFIS.

Ophthalmic Viscoelastic Devices (OVDs) An effective way to keep the iris secured in position and to prevent excessive floppiness and prolapse is to use a super-cohesive OVD such as Healon 5 or Healon GV (Advanced Medical Optics, Santa Ana, Calif.) as a barrier and mechanical plug. Other cohesive OVDs are acceptable; however thesuper-cohesives tend to perform better in this situation (Figure 4). Figure 4. Use of Healon 5 as a mechanical barrier in IFIS. A) Visco-mydriasis with the OVD expanding the pupil and retracting the iris. B) Injecting a plug of Healon 5 to depress the sub-incisional iris and prevent it from prolapsing during phacoemulsification. C) Another plug of OVD is injected prior to cortex removal with the irrigation-aspiration probe. D) a final plug of Healon 5 to keep the iris away from the incision prior to insertion of the intraocular lens implant. Incision Construction and Leakage The clear corneal incision should be placed slightly more anterior than usual. If the incision is too posterior and close to the anterior chamber angle and iris root, there may be an increased tendency for the iris to prolapse. In addition, making a long tunnel length for the incision can provide added stability. The corneal incision should be just large enough to place the phaco probe in the eye, without an excessive amount of wound fluid leakage. The leakage of fluid causes anterior chamber instability and the iris is more likely to prolapse via the leakage sites. The incisions can be checked with fluorescein dye at the end of the case to ensure water-tightness. If there is any doubt as to the sealing of the incision, a 10-0 nylon or vicryl suture should be placed to secure the wound. The Stepwise Approach I have found it most convenient to follow a stepwise approach to the management of IFIS. I routinely use an epinephrine mixture such as Epi-Shugarcaine for these patients. If I still notice excessive iris floppiness, I will add a plug or ring of Healon 5 on top of the iris. If this is not sufficient, a mechanical device such as the Malyugin ring can be inserted. Intraoperative Floppy Iris Syndrome certainly can make cataract surgery more challenging, but with the large spectrum of products available, it can be effectively managed. References Osher RH. Preoperative atropine in IFIS. J Cataract Refract Surg.2007;33:364. Masket S, Belani S. Combined preoperative topical atropine sulfate 1% and intracameral nonpreserved epinephrine hydrochloride 1:4000 [corrected] for management of intraoperative floppy-iris syndrome. J Cataract Refract Surg. 2007;33:580-582. Erratum in: J Cataract Refract Surg. 2007;33:1145. Shugar JK. Use of epinephrine for IFIS prophylaxis. J Cataract Refract Surg. 2006;32:1074-1075. Shugar JK. Prophylaxis for IFIS. J Cataract Refract Surg. 2007;33:942-943. Uday Devgan, M.D., F.A.C.S., is in private practice at the Maloney Vision Institute in Los Angeles, and is chief of Ophthalmology at Olive View - UCLA Medical Center, UCLA School of Medicine. He can be reached at 10921 Wilshire Blvd #900, Los Angeles, CA 90024, tel 310-208-3937, fax 310-208-0169, website: www.maloneyvision.com, email: devgan@ucla.edu . Dr Devgan has no financial interests in the products mentioned. He is a consultant to AMO, B&L, eyeonics, Staar, Allergan, and Ista Pharmaceuticals.

Interestingly, the larger study by Lündstrom et al. showed the opposite, says Dr. Olson — while not statistically significant, the higher rates of endophthalmitis were found to be in patients who had received acrylic IOLs, suggesting a trend in the opposite direction.¹ Because of the lack of randomization and, more importantly, conflicting evidence from the Swedish study, Dr. Olson says that the ESCRS finding provides no overwhelming evidence against silicone and should be viewed as a red herring.

Recommendations for U.S. Surgeons

Dr. Olson concludes that currently, cefuroxime is the only agent that should be used intracamerally. "Nothing else has been studied, and there's nothing else that meets the purity requirements for intraocular injection," he says.

"I'm doing as good a job with frequent topical fluoroquinolones," says Dr. Olson. "I'm using a fourth-generation fluoroquinolone frequently the day of surgery and 4 times a day for 2 weeks postoperative. At this point in time, I don't think there's a difference between the fourth-generation fluoroquinolones. As resistance becomes greater, that might change, but for now that is my recommendation."

Finally, Dr. Olson says that he urges surgeons to lobby the pharmaceutical companies for a safe, effective product for intracameral use. "Whoever does that I think is going to do very well in the market," he says.

References

1. Lündstrom M, Wejde G, Stenevi U, Thorburn W, Montan P. Endophthalmitis after cataract surgery. Ophthalmology. 2007;114:866-870.
2. Barry P, Seal DV, Gettinby G, Lees F, Peterson M, Revie CW; ESCRS Endophthalmitis Study Group. ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery: preliminary report of principal results from a European multicenter study. J Cataract Refract Surg. 2006;32:407-410.
3. Wallin T, Parker J, Jin Y, et al. Cohort study of 27 cases of endophthalmitis at a single institution. J Cataract Refract Surg.2005;31:735-741.

Bimanual or Microcoaxial?

Two surgeons share their experience and opinion about these two platforms for microphaco.

Microsurgery for phacoemulsification represents the next revolution in technique for cataract surgery. When bimanual microsurgery was first introduced, about 5 years ago, the rally behind the push was that surgeons needed to learn smaller incision technique because IOLs that could be inserted into sub–2-mm incisions were on the horizon. Those IOLs are still not here, but microphaco has caught on, mainly because a smaller incision for phaco induces less trauma in the eye and the final incision, even when enlarged to insert the IOL, seals better after surgery is complete, according to two surgeons who spoke to Ophthalmology Management for this article. Newtechnology has also expanded the options for surgeons who wish to phaco through smaller incisions — microcoaxial technology in addition to bimanual. So, how do you decide which technology to employ?

Both Approaches Have Benefits

Rosa Braga-Mele, M.D., F.R.C.S.(c), associate professor of ophthalmology at the University of Toronto and director of Cataract Unit and Surgical Teaching at Mount Sinai Hospital in Toronto, was one of the first surgeons to use bimanual microphaco. Dr. Braga-Mele says that the point of distinction for bimanual, more than the incision size, is the separation of irrigation and aspiration (I&A).

"The splitting of I&A is a big advantage for the mere reason that you have more control over the fluidics in the anterior segment with irrigation through your sideport incision. So you can maneuver your irrigation into areas where you need it — either away from the cornea, toward the capsular bag or away from areas of zonular instability," says

Dr. Braga-Mele. "Conversely, in coaxial phaco, I&A are married, so wherever you go with the phaco needle, you pretty much go with irrigation, which increases the risk for fluid misdirection syndrome in areas of increased turbulence and zonular instability."

Louis "Skip" Nichamin, M.D., medical director of the Laurel Eye Clinic in Brookville, Pa., agrees that there may be some advantages to the separation of I&A.

"When bimanual was first introduced, I too was drawn to the technique," Dr. Nichamin says. "I am also a vitreoretinal surgeon, and we routinely separate infusion from aspiration in the posterior segment, working toward watertight incisions and a nonturbulent state. In cataract surgery, it makes sense that you would want to separate the opposite forces so that you don't push away the material that you are trying to remove."

However, Dr. Nichamin says that the instrumentation for bimanual needs to continue to improve to address the wound leakage that can result with sleeveless phaco and problems obtaining adequate infusion though the chopper.

To address the wound leakage, Dr. Braga-Mele uses a trapezoidal incision. "It's important that the internal diameter of your wound match that of the phaco needle. For instance, if I'm using a 19-gauge system, I'll make my internal diameter 1.4 mm but my external diameter with a trapezoidal blade will be 1.6 mm. This way, I'll have more room to torque and won't be shearing or tearing the cornea," she says.

The main advantage to microcoaxial, both surgeons say, is that there is no learning curve — the technology is the same and the techniques are very similar to standard coaxial surgery. In fact, says Dr. Nichamin, clear-corneal incisions, which have been linked to higher rates of endophthalmitis, are easier to create when they are smaller.

"Clear-corneal wounds are supposed to be square," he says. "The depth should equal the width. When they aren't square, they leak, and the risk for endophthalmitis goes up.¹ When you decrease the width to 2 mm or less, it becomes essentially a no-brainer to create a square incision."

Why Smaller Is Better

Regardless of which approach a surgeon uses for microphaco, the benefits of the smaller incision size will be realized, according to Drs. Braga-Mele and Nichamin. Dr. Braga-Mele makes a 1.4-mm incision with bimanual, using with either the Stellaris (Bausch & Lomb [B&L], Rochester, N.Y.), the Millennium (B&L) or the Sovereign with WhiteStar (Advanced Medical Optics, Santa Ana, Calif.), and Dr. Nichamin makes a 1.8-mm microcoaxial incision with the Stellaris, as does Dr. Braga-Mele, when she uses this approach.

"First of all you have better fluidics and better control with a microincision," Dr. Braga-Mele says. "Second, you have a smaller incision for the procedure so it closes tightly. Third, even though you enlarge your incision to insert the IOL, the area of corneal trauma is the 1.4-mm phaco incision. The extra millimeters of a margin for the enlarged wound seals well— almost as if it didn't happen."

Dr. Nichamin says that further proof that the portion of the wound that is enlarged for the IOL seals remarkably well can be found by looking to secondary or phakic IOL implantation. "For a secondary or phakic IOL we might make a 3.5 incision, slip a lens in and get out — and lo and behold those incisions seal remarkably well. That's because there's virtually no trauma," he says.

Considerations for Each Approach

Instances do exist where the features or nature of each approach tip the scales for certain situations, say the surgeons. With more challenging cases, Dr. Braga-Mele recommends that using a bimanual approach with the split I&A can give a surgeon an edge. "For example, in cases of IFIS, you can keep the irrigation above the plane of the iris, pushing the iris back and down, and still go into the back to remove nuclear pieces with your phaco needle," she says. "With coaxial, you need to go underneath the iris to get the pieces out with I&A, so you tend to push the iris out — resulting in a more floppy iris."

Both surgeons also say that microcoaxial is easier to learn.

"There's no learning curve and no foreign instruments," says Dr. Nichamin.

"Even though I believe in bimanual, I think that surgeons should learn microcoaxial first because it's a more natural transition," Dr. Braga-Mele says, adding, "It's important to note that bimanual fueled a lot of technology advances. IOL development, power modulation and development of microcoaxial — this has all resulted from the bimanual push."

Reference

1. Nichamin L, Chang D, Johnson S, et al. ASCRS White Paper: What is the association between clear corneal incisions and postoperative endophthalmitis? J Cataract Refract Surg.2006;32:1556-1559.

Difficult Case Management

Capsular tension rings, when indicated, can improve outcomes.

Thanks to technological advances in cataract surgery, surgeons have several tools to utilize when faced with more difficult cases. Among these options is the capsular tension ring (CTR), which is used to create a more stable environment in which to operate. I. Howard Fine, M.D., clinical professor of ophthalmology at the Oregon Health and Science University in Portland, Ore., and a founder of Drs. Fine, Hoffman & Packer, was the medical monitor for Morcher GmbH (Stuttgart, Germany) and uses CTRs for all his difficult cases where indicated, but he is concerned that not enough surgeons are using them because of lack of reimbursement.

"We use CTRs in any case where the zonular integrity is compromised," he says. "These devices can change a high-risk case to a routine case. Unfortunately, we have a problem — Medicare isn't willing to pay [the facility fee] for them."

Indications for CTRs

Dr. Fine says that he uses CTRs uniformly for psuedoexfoliation, and 100% of the time for patients who have traumatic zonular injury. He also uses them for all patients who have had previous glaucoma filtering surgery.

"There is frequently a period of hypotony after glaucoma surgery and as a result, the lens may move forward to the point that the zonules have weakened and wrinkling of the capsule occurs," says Dr. Fine.

Additionally, Dr. Fine says that although the cases they see are rare, they will also use a CTR in any patient who has had previous radial keratotomy with more than eight incisions. "This means that the surgeon was pushing to get the maximum amount of effect. And in many cases," he says, "they were going as deep as they could, resulting in a high incidence of micro- and macroperforation, flattening of the chamber and stretching of the zonules."

Technique

Dr. Fine says that controversy exists as to what point of surgery the CTR should go in. However, he maintains that it is best to perform cortical cleaving hydrodissection first and then inject the ring prior to phaco.

"Ike Ahmed published a study demonstrating that a good amount of stress is imposed on the capsule when a CTR is implanted,¹ but in fact, we always inject them through a 1-mm sideport incision," says Dr. Fine. "The injector does not go into the eye, but we control the forces on the capsule using a Lester hook (Katena Products, Inc., Denville, N.J.) in the opposite hand through a second 1-mm sideport incision 90° away. The CTR can be injected from any angle in the eye and any meridian. Our preference is to inject them toward the area of zonular weakness."

Dr. Fine says that his group was the first to inject the rings through a 1-mm sideport incision. "We did that because we use bimanual microincision phaco and CTRs also help to stabilize the lens during the phaco procedure itself. If you have an area with weakened zonules, you are always at risk of extending that area by tearing more zonules and without a ring in, any force that you exert on the capsule is transmitted only to the adjacent zonules," he says.

The CTR distributes any force on the capsule to the entire zonular apparatus, explains Dr. Fine, adding an extra margin of safety.

"We like to put them in before phaco, because it gives us better centration and more safety during the phacoemulsification procedure itself," he says. Dr. Fine adds that the CTR adds long-term stability to the IOL.

Dr. Fine offers the following pearls for using CTRs:
► Always try to have the ring start above the beginning of the zonular weakness so it goes toward the zonular weakness.
► Control the forces on the capsule by pushing or pulling on the ring as it is going in with a Lester hook from the opposite side of the eye.
► Perform cortical cleaving hydrodissection first to free the cortex from the capsule. Avoid stripping the cortex centrally with the ring already in.
► If the CTR is in and it appears to be holding cortex, do not strip the cortex centrally. It is better to strip the cortex tangentially to the capsulorrhexis to allow material to slip more easily around the ring, rather than pulling it perpendicular to the ring.

For most cases where a CTR is indicated, Dr. Fine uses a standard injector for the ring and a Lester hook through the sideport incision 90° away. "If there's more than 200° of zonular dialysis we will probably use an Ahmed Ring Segment or a Cionni Capsular Tension Ring (both Morcher/FCI Ophthalmics, Marshfield Hills, Mass.) that we suture in. But we almost always will start with a regular CTR," he says.

Underutilization of CTRs

Dr. Fine says that he thinks that CTRs are underutilized, primarily because of the added cost. However, Dr. Fine has used over 450 CTRs with uniformly good results, and believes that the cost is worth it, considering the alternative cost of a surgical complication.

"The biggest inefficiency and the biggest cost to the surgeon are complications," he says. "And so I want to prevent complications — I want a good result for every patient and I'm willing to pay more for that patient who's at risk.

"Your reputation is based on your results," Dr. Fine concludes. "No one cares whether you had a difficult case. It's how the patient sees." OM

Reference

1. Ahmed II, Cionni RJ, Kranemann C, Crandall AS. Optimal timing of capsular tension ring implantation: Miyake-Apple video analysis. J Cataract Refract Surg. 2005;31:1809-1813.

Editor's note: Randall J. Olson, M.D., is a consultant for Allergan. He reports no financial interest in the information contained in this article. Rosa Braga-Mele, M.D., F.R.C.S.(c), is a consultant for B&L, AMO and Alcon. She reports no financial interest in the information contained in this article. Louis D. "Skip" Nichamin, M.D., is a medical monitor for B&L. He reports no financial interest in the information contained in this article. I. Howard Fine, M.D., is a consultant for AMO, B&L, iScience, Carl Zeiss Meditec and Omeros Corporation. He receives travel support from Alcon, Eyeonics, STAAR Surgical and Rayner.