Postoperative infectious endophthalmitis is one of the most feared complications of cataract surgery. Prevention of endophthalmitis is of utmost importance, as this severe intraocular infection can lead to permanent vision loss. In this section, we will address postoperative infectious endophthalmitis.
The term endophthalmitis is used for pan-intraocular inflammation involving both the anterior and posterior segments of the eye. It can involve all coats of the eye, as well as adjacent structures. Endophthalmitis can be infectious or sterile, postoperative or endogenous. In postoperative infectious endophthalmitis, the most common organisms are coagulase-negative Staphylococcus, Staphylococcus aureus, and gram negative bacilli. The infection can cause widespread damage to intraocular structures, leading to permanent loss of vision due to direct invasion of the organism into the intraocular structures, as well as due to the robust inflammatory response that ensues. Postoperative endophthalmitis is thought to occur when organisms are introduced into the eye during intraocular surgery. There is some evidence to suggest that the bacteria can influx into the eye after surgery, due to a pressure differential and changes in the flow through the surgical wound. Once in the eye, these organisms replicate and cause widespread infection.
Techniques for infection prophylaxis are aimed at reducing organisms on the ocular surface prior to surgery, reducing the exposure to organisms during the surgical procedure, and eradicating bacteria that enter the eye after cataract surgery is complete.
Prevention of postoperative infectious endophthalmitis is a subject that all intraocular surgeons need to address in their surgical practice. Surgeons institute a wide variety of techniques intended to prevent endophthalmitis, and there is not one single regimen that is universally agreed upon for this purpose. Many studies have been performed to address the efficacy of various prophylactic protocols; however there are numerous inherent complexities in designing high quality clinical trials to address this issue. Endophthalmitis is a rare entity, thus generating high powered studies is challenging. Also, differences in surgical technique vary widely between surgeons, and controlling for these factors can be difficult. Many studies have used surrogate measures for endophthalmitis, such as cultures of periocular flora or anterior chamber sampling. Other studies use animal models, so the results may not be perfectly applicable to the human eye. There are no placebo controlled, double blinded, randomized clinical trials that compare all the currently used methods of endophthalmitis prophylaxis. Therefore it is difficult to make solid recommendations about the gold standard of care. This article will address a variety of methods used for this purpose.
Measures used prior to the surgical procedure are aimed at the reduction of resident flora on the lids, lashes, and the ocular surface. Patients are often instructed to commence meticulous lid hygiene prior to surgery. This treatment is aimed at reducing blepharitis, with the added benefit of enhancing the health of the surface tear film through concomitant treatment of meibomian gland dysfunction. Warm soaks with simple lid scrubs directed at the base of the lashes, utilizing a washcloth with a gentle soap can be instituted. Commercial over-the-counter eyelid cleaners are available for this purpose. Preoperative topical antibiotic regimens are often instituted. There are no well-controlled high quality studies that have definitely shown a benefit in preoperative (or postoperative) topical antibiotics in the prevention of culture-proven endophthalmitis. However, prospective studies have been performed demonstrating reduced cultures of periocular flora with administration of preoperative topical antibiotics . Duration of preoperative administration vary: some surgeons begin dosaging 1 hour prior to surgery, other recommend starting 1-3 days prior to surgery. Some surgeons feel that the extra cost to the patient and society associated with preoperative topical antibiotics and the lack of any data suggesting efficacy are reason to not recommend this regimen. Others worry that preoperative exposure to an antimicrobial agent that will again be used postoperatively may help select for resistant organisms postoperatively, thereby negating any benefit of a preoperative course. Without quality data, a standard-of-care has not been established.
Once the patient is in the operating room, proper sterile preparation of the surgical site is of utmost importance. Instillation of Povidone-Iodine 5% onto the ocular surface at least 3-5 minutes prior to surgery is recommended. This measure has the most long-standing and highest quality evidence to support its efficacy . In addition, sterile preparation of the skin surrounding the surgical eye with Povidone-Iodine 10% is often utilized. Meticulous draping of the lids and eyelashes is performed to achieve a sterile field. Eyelash trimming has not been determined to reduce the bacterial flora and is not recommended .
During cataract surgery, there are several strategies aimed at reducing the risk of endophthalmitis. Meticulous attention should be paid to the construction of the incisions. In modern day phacoemulsification, small incision surgeries have evolved, which often do not require sutures to achieve a water-tight seal at the end of the surgery. However, with the increase in use of clear corneal incisions, there has thought to have been a concomitant rise in the rate of endophthalmitis just after the turn of the century, especially as compared to scleral tunnel incisions (Cooper et al). Defects in the clear corneal wound are postulated to be a risk factor for the development of endophthalmitis, allowing pathogens to enter the anterior chamber after surgery. Wound gape, leak, dehiscence, and vitreous wicks have been found in association with endophthalmitis (Maxwell et al). At the end of surgery, after the eye is re-inflated to physiologic pressure, surgeons will often perform hydration of the wound, Seidel testing for leakage, or check the wounds with a dry sponge to assess for wound leak. There is evidence that the effect of stromal hydration lasted for at least 1 week after surgery. There is also evidence to suggest that slightly elevated intraocular pressure at the end of surgery can help to seal the wound through improvement in the internal architecture (McDonnell et al). When there is evidence of wound leak or concerns about the integrity of the wound, it is prudent to place a single interrupted suture at the end of the surgery. This suture can be removed 1 week after surgery after the wound has a chance to seal, however this wound should be Seidel tested after the suture has been removed, to ensure that the wound has adequately healed.
Some surgeons have advocated the use of antibiotics in the irrigation fluid during surgery, however there are no robust studies showing efficacy. Vancomycin is considered to be a last line of defense for resistant organisms, and widespread use of this powerful antibiotic in routine cataract surgery comes with the risk of development of vancomycin resistant organisms. The use of vancomycin as a prophylactic measure in the irrigation fluid is not recommended on a routine basis.
The only large, prospective, randomized, study examining the efficacy of endophthalmitis prophylaxis was released by the European Society of Cataract and Refractive Surgeons in 2006. The landmark study was based on work by Per Montan, MD in Sweden. The injection of intracameral cefuroxime into the anterior chamber at the end of surgery reduced the occurrence of endophthalmitis (Peter Barry, MD and the ESCRS Endophthalmitis Study Group). Following publication of the ESCRS study, intracameral injection had not been widely adopted in the United States for various reasons, including concerns over the need to compound this medication, the risk of TASS, and the spectrum of activity of this class of antibiotics. A US study published in 2013, however showed similar results to the European study.
Intracameral moxifloxacin has also been used for prophylaxis with a good safety profile, (Lane et al). The potential advantages of moxifloxacin are better Gram negative coverage, in particular enterococcus, and ease of preparation as the drug can be drawn up undiluted from a commercially available preparation. Subconjunctival antibiotic injections have been popular in the past, but there is a paucity of high powered, large controlled studies to make a definitive statement about the role of these injections in the prevention of endophthalmitis.
There is another more recent large study regarding surgical endophthalmitis prophylaxis, but this one conducted by the Kaiser Permanente California program in USA and published in AAO in 2015. Herrington et al. conducted an observational, longitudinal cohort study to examine the effect of topical and injected antibiotics on risk of endophthalmitis in 315 246 cataract procedures realised from 2002 up to 2015. While the general incidence rate of endophthalmitis was low (0.07%), posterior capsular rupture was associated with a 2.68-fold(OR CI 1.89-7.20) increase and age above 80 year was also associated with a 0.46-fold increase (OR CI 1.05-2.05) in the incidence rate of post-operative endophthalmitis. Considering the antibiotic regimens, intracamerular antibiotic with either cefuroxime or moxifloxacin was more effective than using a topical agent alone with a reduction of 42% in the risk rate (OR of 0.58, 0.38-0.91) and definitely more effective than using no antibiotic regimen with a reduction of 70% in the risk rate ( OR 1.95, CI 1.22-3.11). When comparing and analysing intracamerular cefuroxime and moxifloxacin separately, only intracamerular cefuroxime injection proved to be statistically significant in the reduction of post-operative endophthalmitis compared to topical antibiotics only regimen (0.039% and OR 0.53, CI 0.30-0.95) with a slight lower incidence rate than the intracamerular moxiflocaxin injection group (0.047% and OR 0.68, CI 0.36-1.33). This trial also compared isolated intracamerular cefuroxime or moxiflocacin regimen (0.027%, OR 1) with combined intracamerular cefuroxime or moxifloxacin and topical gatifloxacin or ofloxacin antibiotics regimen (0.046%, OR 1.63 CI 0.48-5.47) and it concluded there is no statistically significant advantage in the reduction of endophthalmitis by combining antibiotic regiments and there is even a non-significant increase in the risk of endophthalmitis in the combiantion group, with an apparent 63% increase in the risk rate (OR of 1.63 with CI of 0.48-5.47). From this large study, we can confirm that while endophthalmitis incidence is low (0.07%) it can still be reduced with a maximal reduction being reached by the topical application of povidone-iodine 5% associated with intracamerular injection of antibiotics, particularly cefuroxime, reaching a 47% reduction (OR 0.53, statistically significant).
Postoperative topical antibiotic regimens are intended to reduce the bacterial burden during the time it takes for the surgical incision to re-epithelialize. There are no high quality studies that indisputably demonstrate the effectiveness of this strategy in preventing endophthalmitis. It is often recommended that patients continue their antibiotic drops for 1 week after surgery.
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