Special Report

Controlling Inflammation and Preventing Postoperative Infection

Current thinking on perioperative prophylaxis among anterior segment surgeons.

By Roger F. Steinert, MD

The safety and efficacy of any type of surgery depends, in large part, on effective control of inflammation and prevention of infection. Two main areas of concern for ocular anterior segment surgeons are cystoid macular edema (CME) and endophthalmitis. How surgeons manage these two potential complications continues to evolve.

Targeting Cystoid Macular Edema

CME is an inflammatory reaction believed to be caused by a prostaglandin-mediated breach of the blood-retinal barrier, which leads to capillary leakage and localized thickening of the retina.¹ Because it is recognized as the most common cause of decreased vision following cataract surgery,² even when the surgery is uncomplicated, CME is the key inflammatory reaction surgeons aim to prevent.

The reported incidence of CME following cataract surgery has been variable, and the reason for the variability among studies is not completely understood. However, most studies suggest that clinically significant CME occurs in 1-2% of cases,^3-5 and retinal thickening detectable by angiography or OCT is present in approximately 20% of cases.⁵ Surgeons have become equally concerned about clinically significant and subclinical CME because studies have shown that even low levels of inflammation reduce contrast sensitivity and adversely affect visual acuity.⁶

While there have been no major breakthrough studies to validate a specific protocol for preventing CME following cataract surgery, an accumulation of studies and clinical experience over the past several years has led to changes in how most surgeons approach CME prevention.⁷ What has evolved is the awareness that using both topical steroids and topical NSAIDs postoperatively has a synergistic effect for reducing the rate of CME.⁸ In addition, it appears that using NSAID drops for a period of time prior to surgery as well as after surgery helps to suppress the release of inflammatory mediators, further reducing the risk that they will permeate to the retina and trigger CME.^8-10

The body of available evidence has made the use of NSAIDs before and after routine cataract surgery a common practice among ophthalmic surgeons. Some choose to pre-treat beginning 30 minutes before the procedure, although the dominant strategy is to prescribe NSAID drops from 1 to 3 days prior. (Patients at high risk of developing CME, such as those with a history of iritis, uveitis or diabetes, are typically prescribed both steroid and NSAID drops preoperatively.) Postoperative prophylactic regimens for routine cases vary as well, but it is now common for surgeons to prescribe both steroid and NSAID drops for 4 to 6 weeks after surgery. By following these pre-and postoperative regimens, most surgeons, myself included, have seen a dramatic reduction in postoperative inflammation.

The protocol I use for routine cases in my practice is as follows:

• NSAID drops 4 times per day starting 3 days prior to surgery
• NSAID drops and steroid drops 4 times per day for 1 week postop
• NSAID drops and steroid drops twice per day for the second and third weeks postop
• NSAID drops and steroid drops once per day for the fourth through sixth weeks postop.

Preventing Endophthalmitis

Endophthalmitis, an acute panuveitis that most often results from bacterial infection following penetrating ocular trauma or intraocular surgery, can be sight-threatening and as such is considered a medical emergency.¹¹ Given its potentially devastating effects, and that it can occur after any incisional surgical procedure, preventing it is an important focus for anterior segment surgeons.

The incidence and prevention of endophthalmitis are difficult to study because it occurs infrequently and a large number of surgeon and patient variables are involved with even the most standardized procedures, such as routine cataract surgery. To obtain useful results, a well-designed, large-scale study would need to include an extremely high number of patients and would be cost-prohibitive. Based on the current literature, the incidence of endophthalmitis following routine cataract surgery is believed to be 0.04% to 0.5%.^12-15

For effective prevention, the literature most strongly supports the use of povidone-iodine immediately prior to and perhaps after surgery. Povidone-iodine ophthalmic solution has been shown to effectively reduce the bacterial flora of the eye, i.e., the microbial pathogens present on the patient's external tissues—which is known to be the most common source of infection¹⁶—and is used universally by cataract surgeons around the world.¹⁷

For prophylaxis in addition to povidone-iodine, a range of opinions exists regarding which antibiotics to use and how to use them. In the United States, pre- and postoperative administration of topical antibiotics (used off-label, as most are indicated for the treatment of bacterial conjunctivitis) is a common approach.^18,19 It is based on the rationale that infection can be prevented if antibiotic levels in the aqueous are higher than the minimum inhibitory concentration of bacteria.²⁰

Most U.S. surgeons are moving toward the use of third-and fourth-generation fluoroquinolones as opposed to older drugs. Many studies have been published indicating that fourth-generation fluoroquinolones penetrate more effectively into the eye, resulting in meaningful levels in the anterior chamber.^21-23 To be effective against endophthalmitis, antibiotics must also be capable of eradicating a broad spectrum of bacteria. A recently FDA-approved topical antibiotic, besifloxacin ophthalmic suspension 0.6% (Besivance, Bausch + Lomb), gives surgeons an additional option in this drug category and has been shown to effectively treat gram-positive and gram-negative pathogens.^24-26 In addition to the pre- and postoperative use of topical fluoroquinolones surrounding cataract surgery, there is also general agreement among U.S. surgeons that any signs of eyelid disease should be treated and resolved before a patient undergoes a surgical procedure.

Outside the United States, intracameral administration of antibiotics is a much more widely used strategy. Surgeons who use the intracameral approach cite a body of accumulated evidence, in particular a large multicenter study conducted by the European Society of Cataract and Refractive Surgeons utilizing cefuroxime,²⁷ which indicates intercamerally applying antibiotics at the time of surgery significantly decreases the risk of postoperative endophthalmitis. One study, conducted a year after the ESCRS publication, found that 55% of surgeons in the United Kingdom were using intracameral cefuroxime vs. 6% of the members of the American Society of Cataract and Refractive Surgery.²⁸

The antibiotic protocol I use for routine cases in my practice is as follows:

• fourth-generation fluoroquinolone drops 4 times per day beginning 3 days before surgery
• fourth-generation fluoroquinolone drops 4 times per day for 1 week after surgery.

Patient Education Fosters Compliance

Surgeons can further improve their efforts toward avoiding unwanted postoperative outcomes by helping their patients to be more educated, active partners in their care. In my practice, we do our best to make sure patients understand how to properly use the prescribed medications and why it is important to use them faithfully. We revise the informational forms we hand to patients as needed to ensure they are as clear as possible. Our handouts also include pictures of each medication bottle to help patients distinguish between them. We take the time to explain the information to patients' relatives and caregivers as well.

It is also important to educate patients about the symptoms of CME (e.g., blurred or decreased central vision, difficulty reading, dimness and objects looking distorted) and endophthalmitis (e.g., eye redness, pain, diminished vision, sensitivity to light, ocular discharge and eyelid swelling) and instruct them to contact the office immediately if they experience any of the listed symptoms.

Looking Ahead

From the patient's point of view, the eye drop regimens surgeons prescribe are quite demanding. Elderly patients in particular can become confused about which drops to use at what times and for how long. They may also struggle with dexterity, making the application of drops difficult. Patient compliance issues such as these have prompted efforts to develop topical medications that have increased potency and longer durations of action. These efforts have already come to fruition in the form of some of today's newer NSAIDs and antibiotics.

Hopefully in the not-too-distant future, alternative drug delivery systems, such as implantable depots or contact lenses, will be available so that treatment efficacy is far less dependent on patient compliance. In addition, with regard to antibiotics in particular, surgeons have expressed a desire to have a manufactured antibiotic for intracameral application, which would enhance safety by eliminating the need for drug preparation by compounding pharmacies.

References

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2. Flach AJ. The incidence, pathogenesis and treatment of cystoid macular edema following cataract surgery. Trans Am Ophthalmol Soc 1998;96: 557-634.
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22. Kim DH, Stark WJ, O'Brien TP, Dick JD. Aqueous penetration and biological activity of moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution in cataract surgery patients. Ophthalmology 2005;112(11):1992-1996.
23. Hariprasad SM, Blinder KJ, Shah GK, et al. Penetration pharmacokinetics of topically administered 0.5% moxifloxacin ophthalmic solution in human aqueous and vitreous. Arch Ophthalmol 2005;123:39-44.
24. BESIVANCE Prescribing Information, April 2009.
25. Karpecki P, DePaolis M, Hunter JA, et al. Besifloxacin ophthalmic suspension 0.6% in patients with bacterial conjunctivitis: a multicenter, prospective, randomized, double-masked, vehicle-controlled, 5-day efficacy and safety study. Clin Ther 2009;31(3):514-526.
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28. Gore DM, Angunawela RI, Little BC. United Kingdom survey of antibiotic pro-phylaxis practice after publication of the ESCRS Endophthalmitis Study. J Cataract Refract Surg 2009;35(4):770-773.

Roger F. Steinert, MD, is the Irving H. Leopold Professor and Chair of Ophthalmology, at the University of California, Irvine, professor of Biomedical Engineering and director of the Gavin Herbert Eye Institute. He can be reached at steinert@uci.edu.