Cataract surgery is not only the most common intraocular surgery, but may well be the most common surgery performed annually in the United States. It is estimated that there are approximately 1.5 million cataract surgeries performed in the United States annually. Modern cataract extraction surgery is relatively safe with low incidence of complications, considering the large overall number of surgeries performed, although perioperative complications may affect the visual rehabilitation of a significant number of patients .
Perioperative complications encountered with cataract extraction surgery can be divided into intraoperative and postoperative. The postoperative group can be further subdivided into early and late. Intraoperative complications include posterior capsule rupture, with or without vitreous loss, loss of all or part of the lens nucleus, iris trauma and damage, Descemet’s membrane detachment, wound leak, and suprachoroidal hemorrhage.
Early postoperative complications include pupillary block, hyphema, elevation of the intraocular pressure associated with the use of viscoelastic substances, persistent uveitis (with or without hypopyon), and endophthalmitis. Late postoperative complications include intraocular lens malposition, secondary glaucoma, cystoid macular edema, retinal detachment, and pseudophakic bullous keratopathy .
Postoperative endophthalmitis is a devastating complication of cataract surgery. Modern advances in surgical technique and infection prophylaxis may have reduced the incidence of complications. Nevertheless, current reports indicate an incidence of postoperative endophthalmitis ranging from 0.072%  to 0.17% . The pooled percentage of eyes experiencing postoperative endophthalmitis (weighted by the sample size and, when pertinent, by quality score of the individual studies but not adjusted for variation in duration of follow-up) was 0.13% in a metaanalysis of current published literature . This complication rate implies an incidence of about 1500 cases of postoperative endophthalmitis annually.
The outcome of treatment of endophthalmitis can vary from useful vision to loss of the eye. Identification of the pathogenic organisms and prompt institution of the appropriate treatment does not always prevent serious visual morbidity. Prevention of infectious endophthalmitis remains the most effective means toward better visual outcomes
Source and Access of Pathogens
The major source of the infecting organisms causing postoperative endophthalmitis is the patient’s own eyelid flora. Genetic analysis, using DNA isolation and characterization, has shown an association between the external bacterial flora and the bacteria isolated from vitrectomy specimens in 82% of patients with postoperative endophthalmitis . The most common organisms isolated in this study were Staphylococcus epidermidis, Staphylococcus aureus, and Streptococcus pneumoniae,
The most common organisms found in the eyelids as normal flora are Staphylococcus epidermidis and Staphylococcus aureus [7, 9]. These same organisms are also responsible for 80 to 90% of all bacterial endophthalmitis [1-3, 6, 10] (Table 1). These observations have dictated sterile surgical techniques and isolation of the patient’s ocular adnexa from the operative field as important measures in the prevention of postoperative endophthalmitis.
Complications during cataract extraction and intraocular lens implantation are associated with increased incidence of postoperative endophthalmitis. Posterior capsule rupture either with or without subsequent intraoperative anterior vitrectomy can increase the incidence of postoperative infection by a 5-to IO-fold (from I in 1000 to I in 100 to 200 patients) [4, II, 12]. When the capsular barrier is compromised antibiotic prophylaxis may play an even more significant role in reducing the incidence of postoperative infection. In exogenous bacterial inoculation following cataract extraction surgery, the epithelial break of the surgical incisions appears to be the port of entry for microorganisms into the anterior chamber [13, 14]. In modern small incision, scleral tunnel cataract extraction surgery, draping the conjunctiva over the scleral surgical wound prevents contact between the scleral incision and the nonsterile tear film. This precaution inhibits the direct access to the scleral tunnel incision of microorganisms that may contaminate the tear film postoperatively.
Scleral tunnel and corneal valve incisions have gained wide acceptance among cataract surgeons. In scleral tunneling incisions, a scleral lamellar dissection is carried forward into clear cornea so that the entrance into the anterior chamber forms a watertight internal closure. The posterior placement, narrow profile, and absence of sutures also reduce postoperative astigmatism and improve both short- and long-term keratorefractive stability [14, 15]. Besides these advantages, there is potential for new infectious complications associated with these new surgical techniques. The scleral tunnel lies mostly in relatively nonvascular sclera, creating a potential abscess cavity when inoculated by an infectious organism . Although rare in occurrence, an infection of the scleral tunnel may be difficult to access by topical antimicrobials and may require surgical revision.
The internal corneal lip designed for sutureless surgery acts as a oneway valve, preventing egress of fluid from the anterior chamber. The roof and the floor of the scleral pocket must be in tight apposition to prevent ingress into the anterior chamber. An infective inoculum can be introduced into the anterior chamber by intraoperative or early postoperative fluids ingress through the external opening of the scleral tunnel as a result of external pressure applied to the scleral lip. Eye rubbing, particularly with the eye in extreme infraduction, can promote such a mechanism. An example of this mechanism is the clinical observation of “sterile” endophthalmitis, attributed to the postoperative entry of the subconjunctival antibiotic into the anterior chamber through the one-way valve incision . This influx port to the anterior chamber exists until the surgical wound has reepithelialized. These observations have alerted clinicians to the fact that prophylactic subconjunctival antibiotics can conduit into the eye in scleral tunnel sutureless procedures.
Current Concepts Concerning Infection Prophylaxis
Careful inspection of the patient’s eyelids preoperatively will often reveal significant underlying disease . Significant preoperative blepharitis and meibomitis raise the issue of preoperative treatment. Lid hygiene in conjunction with topical antibiotic ointments or systemic antibiotics can be very effective in reducing the microbial counts of the eyelid flora preopera- tively [19,20].
As mentioned previously the eyelid flora harbors most of the organisms responsible for postoperative infections . Propping the patient’s periocular skin with 5% povidone iodine solution with special attention given to propping of the eyelashes addresses the infectious risks described above .
Bacterial colonization of the patient’s ocular adnexa can orginate from preexisting prosthetic devices (contact lenses, prosthetic scleral shell) and can act as a harbor for cataract wound contamination . Special caution is warranted for the intraoperative isolation of such potential adnexal infectious sources, as well as their perioperative disinfection with operative scrubbing techniques and antimicrobial use.
Empiric prophylactic treatment has become common practice with its aim to prevent severe ocular morbitity associated with postoperative endophthalmitis. Antibiotic treatment of a potential infectious inoculum during cataract surgery is commonly used as means of prophylaxis, despite treatment of preexisting eyelid disease, sterilization of the operative field, and draping of the eyelid cilia (Table 2). Routine aqueous humor samples taken upon completion of uncomplicated consecutive cataract extractions have yielded a positive culture in up to 43% of patients [23, 24]. These observations suggest that even in uncomplicated procedures with routine sterility measures taken a significant number of eyes are inoculated with external bacterial flora. Surprisingly, the incidence of endophthalmitis is far less common, suggesting that natural immune processes can battle routine intra- and postoperative bacterial inoculations. Postoperative prophylactic management of cataract patients with antibiotics may eradicate such inoculations.
Perioperative Antibiotic Prophylaxis
There is no agreement over the regimen used in preoperative, intraoperative, or postoperative antibiotic prophylaxis in cataract surgery. The older literature documents a significant reduction in endophthalmitis with the use of perioperative antibiotics [25, 26]. The use of the aminoglycosides tobramycin or gentamycin as monotherapy following cataract extraction has been a popular practice. Their adverse effects include epithelial and retinal toxicity. Their activity is good against Gram-negative organisms and Staphylococcus aureus. They are poorly active against Staphylococcus epidermidis and Streptococcus pneumoniae, which are responsible for a large fraction of postoperative endophthalmitis cases . Therefore, the use of a single agent with a specific antibacterial spectrum of action may not provide adequate prophylaxis for postoperative infection. Fluoroquinolones are broad-spectrum antibiotics and can be used for endophthalmitis prophylaxis. They have low toxicity along with a broad spectrum of antibacterial activity. In oral form both ciprofloxacin and ofloxacin have excellent intravitreal penetration [27-29]. Ofloxacin has higher internal solubility that may provide an added advantage to postoperative prophylaxis, by contributing higher topically available concentrations and better penetration into the eye.
Recent concern has been raised regarding the occurrence of antibiotic resistance to these broad-spectrum antimicrobials with their widespread use. It appears that the small number of bacteria in the tear film, as well as the very high concentration accomplished with topical administration of these antibiotics, makes resistance following ocular administration much less likely compared to systemic use.
Subconjunctival antibiotics used at the completion of cataract surgery have been a common form of perioperative prophylaxis of infection since the mid-1950s; from the beginning, their use has been controversial . Several randomized prospective studies have indicated no advantage to topical treatment in the prevention of postoperative infections following cataract extraction [31, 32]. Potential toxicity with the use of these agents is a major disadvantage of their use. Use of subconjunctival gentamycin has been associated with conjunctival hyperemia, edema, and capillary closure . Significant higher degrees of conjunctival injection and anterior chamber activity have been noted with subconjunctival injections [17, 34]. Retinal toxicity following subconjunctival antibiotic injections has emerged as a very significant concern and has been suggested in several studies [35, 36]. The use of subconjunctival antibiotics for the prophylaxis of postoperative infections remains subject to the surgeon’s personal preference.
With the recent transition of cataract extraction from extracapsular to smaller incision phacoemulsification, several cataract surgeons have begun the use of antibiotics in the irrigation fluid used during phacoemulsification. This technique has been suggested mainly by high-volume surgeons on the basis of a small number of reports suggesting their effectiveness [37, 38]. The antibiotics used are commonly an aminoglycoside or a cephalosporine. Continuous flow of antibiotic during phacoemulsification intraocularly does provide the theoretical advantage of sterilization of any infectious inoculum, although in practice the amount of antibiotic that is routinely used may be insufficient for this purpose [38A]. However, the exposure of intraocular tissues and subsequent toxicity would depend on the duration and amount of irrigation fluid used during the procedure, parameters that are not quite standardized for each individual surgery and surgeon. There is potential for extensive toxicity of the corneal endothelium, trabecular meshwork, and retina, especially in cases where the posterior capsule is compromised. The potential for dosage error in the irrigation fluid preparation can result in devastating complications. In most cases the actual preparation of the irrigation fluid/antibiotic mixture is not even done by the surgeon.
Intraoperative antibiotic administration in the irrigation fluid during phacoemulsification is another form of perioperative prophylaxis with questionable efficacy and serious potential complications. Their use remains again to the preference and clinical experience of the individual surgeon, although the available literature is not quite convincing.
Diagnosis and Management of Postoperative Infections
The diagnosis of endophthalmitis is suspected in any patient with excessive intraocular inflammation following cataract extraction. The predominant symptoms are decreased vision and pain . Once the diagnosis of endophthalmitis is suspected prompt management can improve the prognosis . Postoperative Propionibacterium endophthalmitis is a form of delayed-onset infection often confused with persistent postoperative inflammation in the past. Recent reports have increased the clinical awareness for this entity where surgical management is associated with little recurrence potential and relatively good prognosis [41, 42]. As determined by the outcome of endophthalmitis management, early suspicion and diagnosis plays an essential role in the eventual visual rehabilitation of the patient.
Current guidelines consist of a complete ophthalmic evaluation including ophthalmoscopy and posterior segment ultrasonography if needed . Intraocular cultures, taken at that point may confirm the diagnosis and guide medical treatment. Vitreous cultures obtained by pars plana vitrectomy or vitreous aspirate appear to have a higher positive yield than anterior chamber cultures alone . Inoculation of the aqueous or vitreous specimen on multiple culture media may optimize the culture yield. Customarily, the media used are blood agar and chocolate agar for identification of bacteria, Sabouraud’s agar for isolation of fungal organisms, and thioglycolate breath for isolation of anaerobic organisms.
Pars plana vitrectomy can be utilized as a diagnostic as well as a treatment remedy in the management of endophthalmitis. The theoretical advantages of vitrectomy in the management of infectious endophthalmitis include the debulking of the infectious load and removal of toxins, as well as the improved penetration and distribution of the intraocular medications as they can be administered intravitreally during the procedure. Disadvantages include the risks and complications associated with any vitrectomy . The consensus regarding therapeutic vitrectomy, prior to the Endophthalmitis Vitrectomy Study, was utilizing pars plana vitrectomy when there is extensive vitreous inflammation precluding the visualization of the retina and also impairing significantly the patient’s visual acuity .
Although not the primary focus of this article, the antibiotic treatment of endophthalmitis currently consists of intravitreal antibiotic administration. The most popular antibiotic regimen consists of ceftazidime (2.25mg/O.1 ml) in conjunction with vancomycin (1 mg/O.1 ml) with or without the addition of intravitreal corticosteroid administration (dexamethasone 0.4 mg/O.1 ml). It appears that culture-negative and Staphylococcal endophthalmitis have better prognosis than Streptococcal, Hemophilus, or Bacillus infections [18, 43, 44, 46].
The prognosis of postoperative endophthalmitis is closely related to the type of infective organism as noted above, as well as the length of time between onset of infection and initiation of therapy. Traditionally, the visual outcomes are divided in better than 20/400 or worse than 20/400 visual acuity. Overall success of treatment of postcataract surgery endophthalmitis indicates that vision of equal to or better than 20/400 is achieved in 44% to 73% of eyes [40, 43].
Finally, the results of the recent Endophthalmitis Vitrectomy Study suggest that the use of systemic antibiotics along with intravitrea does not affect the prognosis and could be omitted. Also, immediate vitrectomy after the diagnosis of endophthalmitis benefited only patients with poor visual acuity (light perception) at the time of diagnosis . In this multicenter prospective study of 420 patients, the intravitreal antibiotics used were amikacin (0.4 mg in O.I ml, and vancomycin 1.0 mg in O.I ml). The systemic antibiotics used in this trial, however, are not effective against Staphylococcus epidermidis, the most common cause of postoperative endophthalmitis. This study suggests that the omission of systemic antibiotic treatment and, for that reason, inpatient care, can reduce toxic effects and the cost of care. Also, immediate vitrectomy in patients with visual acuity better than light perception is probably not necessary, but may offer a substantial benefit to the patients that present with light perception-only vision. In summary, postoperative endophthalmitis can be a devastating complication of cataract surgery. Recent advances in surgical technique have introduced new mechanisms for pathogenic organisms to cause infection. The infectious source and its access into the eye are now better understood. This review focused on current concepts involving the incidence, etiology, intraoperative and postoperative risks, antibiotic prophylaxis and diagno- sis, and management of infection following cataract surgery. Additional research may clarify and improve the role of prophylactic intraoperative and postoperative antibiotic administration.
Anastasios John Kanellopoulos, MD