Postoperative Endophthalmitis: Prevention and Management

Combating this devastating complication of cataract surgery.

BY STEVEN M. SILVERSTEIN, M.D., F.A.C.S.

Endophthalmitis, though relatively uncommon with a reported incidence between 0.08% and 0.3%,¹ is considered the most potentially devastating, yet perhaps the most preventable complication of modern day cataract surgery. Following a decade of relative stability in the 1980s, the incidence of endophthalmitis following cataract surgery has been gradually on the rise since the early to mid 1990s. It is common to point out, that from an epidemiologic perspective, this increase in occurrence coincides with the introduction of the clear corneal incision (CCI) in 1992. It is certainly true that wound location and architecture play a role, yet there are additional risk factors that make equally important contributions to this rise in incidence. In this article, I will discuss the causes of postoperative endophthalmitis and provide guidance for the prevention and management of this, one of the most serious of all cataract surgery complications.

Though not the direct subject of this article, I should also point out that with the many thousands of VEGF-inhibitor and steroid injections now being performed, the incidence of endophthalmitis is increasing in this arena, and endophthalmitis (early or late onset) following trabeculectomy and other glaucoma filtering procedures has always been of concern. Most recently, we are seeing a rise in the number of endophthalmitis cases caused by methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE) infections, for which our normal routine of antibiotic therapy may not be effective.

The subjective symptoms of endophthalmitis may include pain, photophobia, fever and decreased vision. Patients often present with the clinical findings of conjunctival hyperemia, chemosis, discharge, lid edema and erythema, associated corneal edema and infiltrate, anterior chamber reaction (mild in chronic cases such as that seen with the bacteria p. acnes, or in those patients with suppressed immunocompetency), or severe, demonstrating a fibrinoid reaction and/or hypopyon formation), and vitritis, rarely with an associated retinitis or papillitis. Most cases are identified within the first 4 to 7 days postoperatively. Though bacteria, fungi, viruses and even parasites have all been implicated, by far the most common underlying culture-proven etiology include gram positive microorganisms.

Endophthalmitis may also be non-infectious (referred to as sterile endophthalmitis) if no identifying organism is identified, and the inflammatory response is treated successfully with steroidal and other anti-inflammatory medication. Toxic anterior segment syndrome (TASS), is one such example and is most commonly associated with instrument-cleaning techniques thought to be due to retained detergent material or denatured viscoelastic caused by an enzymatic cleaner.²

Key Factors in the Endophthalmitis Equation: Wound Architecture

As mentioned in the introduction, wound location and construction are frequently implicated as being a principal cause of postoperative endophthalmitis, particularly since I. Howard Fine, M.D., introduced us to the clear corneal incision in 1992. He and his colleagues have presented their own data showing that with proper use of this technique, they have not seen a single incidence of endophthalmitis in more than 10,000 cases.³ However, numerous national and international studies have reported a significant increase in the incidence of endophthalmitis in cases employing this method when compared to those in which a scleral tunnel or other non-clear corneal technique was used.

Classic endophthalmitis with hypopyon, corneal infiltrate and edema, a fibrinoid anterior chamber reaction and hyperemic eye.

Investigations performed and reported by Paul H. Ernest, M.D., concluded that due to differences in wound healing at the limbus vs. in the avascular clear cornea, limbal-based incisions heal within 7 days, whereas CCIs require 30 to 60 days. This, he believes, is due to fibroblastic activity seen at the limbus, but not in the avascular cornea, which requires keratocytes for complete wound healing.³

In a retrospective study performed by Peter J. McDonnell, M.D., Mehran Taban, M.D., et al, a review of 215 cataract papers, encompassing more than three million cataract surgeries performed between 1963 and 2003, revealed an increase of at least 2.5 times in the rate of acute postoperative endophthalmitis during the decade, which coincides with the introduction and adoption of the CCI technique.⁴ In another study that was also performed by Drs. McDonnell and Taban, et al, the potential for ocular surface fluid to ingress into the anterior chamber of cadaveric human eyes with CCIs at varying intraocular pressures using India ink, was eloquently demonstrated. They concluded that under certain circumstances, CCIs appeared to be compromised, not permitting fluid to leak out, but allowing some fluid to leak in.⁵

Remember that there are multiple variations of CCI technique in which the type of blade (stainless steel vs. diamond, trapezoidal, etc.), width and chord length, shape of wound (square vs. rectangular), proximity from the limbus, superior vs. temporal wound position, and "dimpling down," all play important roles in wound integrity. Dimpling down refers to an initial straight-ahead anterior stromal entry, followed by an immediate angling downward toward the macula, at which point the tip of the keratome creates a dimple in the corneal stroma. This maneuver is well-documented to produce a hinged flap which, after properly pressurizing the anterior chamber with BSS, creates a relatively self-sealing wound.

A white paper published by the American Society of Cataract and Refractive Surgery in 2006 examined the relationship between CCIs and the risk of postoperative endophthalmitis. The authors concluded that "with appropriate use of aseptic methods, including careful draping, chemoprophylaxis and particularly CCI design, construction, and sealing — the risk for infection can be appropriately low."⁶

Antibiotic Usage, Prophylaxis and Resistance

The controversy surrounding the use of peri-operative antibiotics rages on. In the United States, the application of pre- and postoperative topical antibiotics is standard of care, while this is not always the case in other countries. Mark B. Abelson, M.D., and others have taught us that the most common organisms responsible for endophthalmitis following cataract surgery include the gram positive bacteria staph epidermidis, staph aureus and strep species, followed by pseudomonas aeruginosa, proteus and haemophilus microorganisms.⁷ These and other common pathogens, such as mycobacteria, are ubiquitous, being isolated in water supplies, as well as part of our normal eyelid, ocular surface and nasal flora.⁸ The (over) use of antibiotics has created serious problems with resistance, leading to the development of the fourth-generation fluoroquinolones, gatifloxacin (Zymar, Allergan) and moxifloxacin (Vigamox, Alcon). In addition to superior ocular penetration and efficacy with a broader spectrum of activity than the third-generation fluoroquinolones, this group of antibiotics temporarily strengthens our battle against bacterial resistance due to its dual mechanism of action via inhibition of both DNA gyrase and topoisomerase IV.⁹

Presenting in Lancashire, England, in 2004, Manita S. Gupta, M.D., showed data to support the use of vancomycin (50mg/500ml of BSS) added to the irrigation solution at the time of cataract surgery. Dr. Gupta evaluated two groups, each with a cohort of over 3,000 patients between March 2000 and April 2002. One group received vancomycin in the irrigating solution and the other received no antibiotic in the irrigant. The study revealed a decline in postoperative endophthalmitis from 0.4% to 0.16%.¹⁰ Similarly, James Gills, M.D., in Tarpon Springs, Fla., reported no cases of endophthalmitis in 25,000 surgeries after he began placing vancomycin in the BSS irrigating bottle.¹¹

More recently, a European examination that included many surgical sites in multiple countries, evaluated the use of intracameral cefuroxime. This large study concluded that the use of this agent led to a significant decline in the incidence of postoperative endophthalmitis.¹² This study has been under great scrutiny in the United States. Critics of the data point to a relative lack of standardization and the fact that the use of pre- and postoperative topical antibiotics is not the standard of care in Europe.

A newly reported study by Patrick Yu-Wai-Man, M.D., et al, reported a statistically significant decrease in the number of cases of endophthalmitis in patients administered intracameral cefuroxime when compared to those receiving a subconjunctival injection of cefuroxime at the time of cataract surgery.¹³

Indeed, all studies investigating the incidence and cause-and-effect relationships of endophthalmitis are limited by sample size (a significant prospective study would require at least 100,000 cases of endophthalmitis), surgeon/technical variability and bias. Therefore, most studies with a significant cohort have been retrospective in design.

Sterile Technique

In discussions regarding appropriate practices toward the prevention of endophthalmitis, the first point on every list focuses on the importance of proper preoperative sterile technique, which must include the careful and repeated application of periocular 5% to 10% povidone-iodine, as well as the flushing of the conjunctiva with the same solution. In addition, Samuel Masket, M.D., and others have highlighted the importance of meticulous draping, particularly when sequestering the lashes with steri-strips, a bladed lid speculum or both.¹⁴

Other Risk Factors

The following additional factors have also been implicated in the incidence of endophthalmitis following cataract surgery:
► capsular tear and vitreous loss, unintentional aphakia
► prolonged surgical time
► immunocompetency, including a history of diabetes, recent immunosuppression, active systemic infection
► TASS-related issues (discussed previously) inadequate instrument sterilization
► wound burn
► IOL or haptic polymers
► prosthetic orbital implant in the contralateral eye.

When Treatment Is Required

When endophthalmitis is suspected or identified, immediate referral to a vitreoretinal specialist (if one is available) is critical. Though the treatment strategy is variable, vitreous tap for culture and sensitivity followed by the intravitreal injection of vancomycin and amikacin or ceftazidime is the most common regimen.¹⁵ Often, subconjunctival and/or systemic antibiotics are also administered. The intravitreal injection of a steroid is sometimes added to the cocktail in order to minimize the risk of further scarring and damage caused by the eye's own inflammatory response. Topical administration of a fourth-generation fluoroquinolone, a fortified antibiotic, or both, is initiated and titrated based upon culture and sensitivity results, or the clinical response to treatment.

Vitrectomy, as per the Endophthalmitis Vitrectomy Study, is usually performed in advanced cases. In this study, vitrectomy performed in patients with hand motion or better acuity had no advantage over vitreous tap, but was found to have a threefold improvement in eyes with light perception only.¹⁶

Recommendations for Prevention

Though research and discussion surrounding endophthalmitis is intensely focused on the pre-, intra- and postoperative milieu, it is also well understood that the patient and or his/her caregiver play important roles in the transfer of infectious microorganisms to the eye. Therefore, careful emphasis should be placed on proper hygiene and the proper care, storage and administration of eye drops, both during the immediate postop education session as well as a reminder at the time of subsequent postoperative office visits. This is particularly important for patients receiving their care in a nursing home or visiting nurse setting. These instructions should be clearly defined on the postop information sheet.

Special attention should also be given pre- and postoperatively to the control of blepharitis and meibomitis.

In regard to wound construction and architecture, many recommendations have found their way to the literature. Stromal hydration of the wound margins at the conclusion of surgery further ensure a relatively watertight, self-sealing incision. Dr. Fine and his group, employing anterior segment OCT, have demonstrated that this deliberate wound hydration remains present for at least 24 hours.³ I advocate stromal hydration of both the primary surgical wound as well as the sideport incision. An incision which appears to be well sealed at the conclusion of surgery may still leak postoperatively due to the mechanical forces created on both wounds with eye rubbing and blinking, which cause the incisions to fish mouth. Many surgeons place a single 10-0 criss-cross nylon suture in the CCI for 1 to 4 weeks. Keep the internal wound length as long as possible; at least 2 mm is considered ideal.³

Endophthalmitis with corneal infiltration involving the surgical incision site.

Culture any eye suspected of having an infectious conjunctivitis prior to surgery.

Consider providing fresh bottles of chronic medications postoperatively, such as glaucoma drops and artificial tears.

Treat low-risk patients with a bacteriocidal antibiotic for at least 2 days prior and on the day of surgery (longer in patients considered at higher risk, such as patients with diabetes, those on immunosuppression therapy and patients with a history of a recent systemic infection).

Review the procedures for proper hygiene and the administration of pre- and postoperative drops with your OR or ambulatory surgery center personnel.

Save all BSS bottles and other injectables used in each patient's surgery for 1 week. If endophthalmitis is suspected, sending these fluids and viscoelastics for culture and sensitivity may provide guidance toward appropriate therapy earlier than the clinical course may suggest.

Some physicians such as William J. Oktavec, M.D., in St. Augustine, Fla., advocate the continuous placement of ultraviolet radiation units in the operating rooms in an attempt to kill mold and bacteria using electrostatic filters.¹

Looking Ahead

As IOL technology enters its next generation of implantable lenses through sub-2 mm incisions, greater emphasis will be placed on bimanual or microincisional coaxial surgical technique, which will shift the paradigm to significantly smaller wound characteristics. It will be most interesting to learn what impact this change will have on the incidence of postoperative endophthalmitis. New developments toward improving antibiotic penetration, efficacy and resistance may further assist in lowering the incidence of this disease, as well as newly designed multicenter studies which shed light upon the proper usage of antibiotics (i.e., in the irrigating solution and/or intracamerally).

Finally, several studies are examining the benefit of sealing the cataract incisions with tissue adhesive, in order to produce an immediate watertight seal. OM

References

1. Riddle JS. Heading off acute postop endophthalmitis. Rev Ophthalmol. 2003;10. http://www.revophth.com/index.asp?page=1_395.htm. Accessed April 3, 2008.
2. American Society of Cataract and Refractive Surgery; American Society of Ophthalmic Registered Nurses. Recommended practices for cleaning and sterilizing intraocular surgical instruments. Insight. 2007;32:22-28.
3. Guttman C. Debate continues on role of incision type in endophthalmitis. Ophthalmol Times. 2008 Mar 1. http://ophthalmologytimes.modernmedicine.com/ophthalmologytimes/Cataract/Debate-continues-on-role-of-incisiontype-in-endop/ArticleStandard/Article/detail/500235. Accessed April 3, 2008.
4. Guttman C. Clear corneal incision linked to rising endophthalmitis risk: surgeons urged to take special care in construction of incision for cataract surgery. Ophthalmol Times. 2004 Jun 1. http://www.accessmylibrary.com/coms2/summary_0286-31133191_ITM. Accessed April 3, 2008.
5. Taban M, Sarayba MA, Ignacio TS, Behrens A, McDonnell PJ. Ingress of India ink into the anterior chamber through sutureless clear corneal cataract wounds. Arch Ophthalmol. 2005;123:643-648.
6. Nichamin LD, Chang DF, Johnson SH, et al; American Society of Cataract and Refractive Surgery Cataract Clinical Committee. ASCRS White Paper: What is the association between clear corneal cataract incisions and postoperative endophthalmitis? J Cataract Refract Surg. 2006;32:1556-1559.
7. Abelson M, Kennedy K, Lilyestrom L. Unraveling the mystery of endophthalmitis: a look at what we know about this dreaded complication and steps that might help prevent it. Rev Ophthalmol. 2004;11. http://www.revophth.com/index.asp? page=1_13692.htm. Accessed April 3, 2008.
8. Gaining Perspective in Incidence, Prevention and Treatment of Infection: Francis S. Mah, M.D.: Ophthalmology Management: April, 2006.
9. Roberts C. Penetration of the fourth-generation fluoroquinolones: consider risks vs. benefits. Ther Updates Ophthalmol. 2005;6:1.
10. Gupta MS, Guttman, C. Intracameral agent reduces incidence of endophthalmitis. Ophthalmol Times. 2004;29:52-53.
11. Gills JP. Filters and antibiotics in irrigating solution for cataract surgery. J Cataract Refract Surg. 1991;17:385.
12. 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.
13. Yu-Wai-Man P, Morgan SJ, Hildreth AJ, Steel DH, Allen D. Efficacy of intracameral and subconjunctival cefuroxime in preventing endophthalmitis after cataract surgery. J Cataract Refract Surg. 2008;34:447-451.
14. Masket S. Lecture at the Johns Hopkins Lecture Series, Current Concepts in Ophthalmology; Vail, Colo. March 2006.
15. Abelson M, Forbes M. The enigma of endophthalmitis. Rev Ophthalmology. 2004;11. http://www.revophth.com/index.asp?page=1_605.htm. Accessed April 3, 2008.
16. The Endophthalmitis Vitrectomy Study Group. Results of the Endophthalmitis Vitrectomy Study. A randomized trial of immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis. Arch Ophthalmol. 1995;113:1479-1496.

Steven M. Silverstein, M.D., F.A.C.S., is a partner in Silverstein Eye Centers, P.C., in Kansas City, Mo. He is also clinical professor of ophthalmology at the University of Missouri Kansas City Medical School and clinical professor of ophthalmology at the University of Health Sciences. He can be reached via e-mail at ssilverstein@silversteineyecenters.com