Pupil Dilatation

Sympathomimetic mydriatic agents (phenylephrine 2.5%) and parasympatholytic cycloplegics (tropicamide or cyclopentolate 1.0%) usually are used together before extracapsular nuclear expression, phacoemulsification (phaco), or femtosecond laser-assisted cataract surgery (FLACS). Used excessively, sympathomimetics increase the possibility of a severe systemic hypertensive response with associated systemic risks in older adults. For this reason, phenylephrine 10% is not recommended routinely. To assist adequate pupil dilatation, pilocarpine and other cholinergic miotics should be discontinued 12 to 24 hours before surgery (approximately twice the expected duration of action of the specific agent).

Topical nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in cataract surgery to prevent pupillary miosis, reduce surgically induced inflammation, and prevent postoperative cystoid macular edema. NSAIDs inhibit cyclooxygenase, decreasing prostaglandin synthesis from arachidonic acid. Prostaglandin E2 (PGE2) enhances the constrictor action of the iris sphincter through a mechanism not dependent on cholinergic receptors. Topical flurbiprofen 0.03%, the first agent used for this indication, was demonstrated to be clinically superior to topical indomethacin 1%. Currently, diclofenac 0.1%, ketorolac 0.5%, and nepafenac 0.1% have the same indication. Although diclofenac and flurbiprofen adequately maintain mydriasis during surgery, ketorolac appears to inhibit miosis more effectively.

Intracameral mydriatic solutions using cyclopentolate 0.1%, phenylephrine 1.5%, xylocaine 1% or tropicamide 0.5%, phenylephrine 5%, and diclofenac 0.1%, in preservative-free solutions are safe to the corneal endothelium and effective in producing and maintaining pupillary dilatation and are used in various combinations ( Table 5.7.2 ). Effective redilatation has also occurred with use of these mydriatics intracamerally during surgery on contracted pupils.

Anti-infective Prophylaxis

No worldwide consensus exists on prophylactic topical antibiotics in cataract surgery, although their use has been an accepted practice for decades. A large randomized study of preoperative topical antibiotics for the prevention of endophthalmitis has yet to be carried out. The most important source of potential infectious organisms is the patient’s own natural conjunctival and skin flora. Intraoperative cultures indicate that 5% of intraocular surgeries result in measurable anterior chamber contamination from indigenous flora, but the vast majority of patients develop no adverse clinical sequelae. Cultures from the conjunctiva and anterior chamber of patients who subsequently developed endophthalmitis usually yielded the same bacterial strains. Staphylococci ( Staphylococcus epidermidis and S. aureus ), diphtheroids ( Corynebacterium ), streptococci ( Streptococcus viridans ), and Gram-negative bacilli (pseudomonas, serratia, and enterobacteriaceae species, anaerobic Propionibacterium acnes, and others) are the most common infecting agents in decreasing order of occurrence. Medications should adequately cover these bacteria during the operative and perioperative periods. Before cataract surgery, topical anti-infective regimens historically included gramicidin–neomycin–polymyxin B sulfate; aminoglycosides, such as gentamicin or tobramycin (which provide Gram-negative and pseudomonas coverage); and the fluoroquinolones—ciprofloxacin, norfloxacin, ofloxacin 0.3% or levofloxacin 0.5%. Of these, levofloxacin provided superior coverage and anterior-chamber penetration, before fourth-generation fluoroquinolone (G4FQ) became available. The G4FQs gatifloxacin 0.3% and moxifloxacin 0.5% are currently preferred because they offer better penetration compared with previous generations (moxifloxacin appears to be better than gatifloxacin), broader-spectrum coverage, lower incidence of bacterial resistance, and equal safety. Antibacterial prophylaxis for cataract surgery has become an increasingly prominent issue after the confirmation of increased incidence of postoperative endophthalmitis with clear corneal incisions. Retrospective studies indicate that endophthalmitis rates are lower with the postoperative use of topical G4FQ compared with historical controls. There have been no prospective studies determining ideal dosing for prophylactic use, but some authors have suggested that administration of antibiotics 3 days preoperatively may yield superior intraocular drug levels at surgery. A similar consensus of antibiotic use 1 to 3 days preoperatively occurred in the 2007 ASCRS member survey. There appeared to be no difference in bacterial load with the use of moxifloxacin either 1 or 3 days preoperatively. Several recent cases raised concerns that prophylactic use of potent antibiotics in healthy patients with cataract may lead to bacterial resistance, thereby theoretically increasing the risk of postoperative infection with a resistant strain in patients so treated. Ong-Tone demonstrated that the aqueous concentration of antibiotics administered topically is maximal when the drops are given within 2 hours of surgery, rendering their administration days in advance unnecessary. Therefore, topical antibiotic administration every 15 minutes for three to four doses before surgery seems optimal, yielding the highest anterior chamber concentration, which permits insufficient time for resistant strains to take hold. On a population scale, the authoritative Medical Letter has stated that the risk of causing resistant strains from the use of antibiotics in ophthalmology is minimal because of the low number of viable bacteria exposed to the agent; therefore, long-term preoperative administration of topical antibiotics may select out existing resistant strains but cannot induce new ones.

Subconjunctival injections of antibiotics has been shown to reach adequate aqueous humor concentrations. Retrospective studies have found that subconjunctival antibiotics are effective at lowering the incidence of postoperative endophthalmitis.

Complete conjunctival sterility is not achievable with the use of preoperative antibiotics alone. The topical nonselective antiseptic agent povidone-iodine 5%, instilled as a single drop 10 to 30 minutes before surgery, is one of the most effective measures to decrease this bacterial flora. In fact, a recent prospective study found that topical moxifloxacin 0.5% lacked a significant additive effect on the preoperative reduction of conjunctival bacterial colonization beyond the effect of povidone-iodine 5%. No consensus currently exists with regard to the use of 5% or 10% concentration of povidone-iodine. In the event of a known or suspected iodine allergy, polyhexidine or chlorhexidine gluconate is a well-tolerated alternative, and chlorhexidine is used as a standard in Sweden instead of povidone-iodine.

Novel approaches for prophylaxis may be on the horizon, including drug delivery nanoparticles and presoaked intraocular lenses (IOLs) with antibiotic.

Additives to Irrigating Solutions, Intracameral Antibiotics, and Other Intraocular Drugs Used During the Surgical Procedure

Table 5.7.3 gives a summary of commonly used intraoperative pharmacotherapeutic routines. In general, the addition of antibiotics, mydriatics, epinephrine (adrenaline), or lidocaine (lignocaine) is not recommended by the companies that produce irrigating solutions for cataract surgery because any effect on stabilizers and preservatives in the solutions could alter their pH, chemical balance, or osmolarity and influence the potential toxicities of both the irrigating solution and the additive. Caution is advised with any alteration to commercial irrigating solutions.

To prevent intraoperative miosis, nonpreserved epinephrine (1 : 1000) 0.5 mL/500 mL is the most frequently used additive. This concentration appears nontoxic to the corneal endothelium and allows normal endothelial function.

A new U.S. Food and Drug Administration (FDA)–approved combination drug, phenylephrine 1.0%–ketorolac 0.3% (Omidria) has been studied for the treatment of intraoperative miosis and postoperative ocular pain. The study found that this medication was better than placebo in maintaining mydriasis and preventing postoperative pain in the early postoperative period.

Insufficient evidence exists to support the addition of antibiotics into the irrigating solution, although smaller studies previously demonstrated a benefit. Vancomycin (20 µg/mL (0.02 mg/mL)) combined with gentamicin (8 µg/mL (0.008 mg/mL)) in the irrigating solution, has been reported to eradicate Gram-positive, coagulase-negative micrococci, with minimal associated complications. Gentamicin alone has been used intraoperatively in the dosage range of 8 to 80 µg/mL in the irrigating solution, which avoids retinal toxicity and also decreases the intracameral bacterial load. However, a recent large study showed no significant benefit of antibiotics added to the irrigating solution, whereas intracameral antibiotics were very effective.

The postoperative capsular bag is a sequestered avascular site that harbors a foreign body (the intraocular lens) and may act as the nidus for most cases of endophthalmitis. Introduced by James Gills in the early 1990s, intracameral vancomycin (1 mg in 0.1 mL balanced salt solution [BSS]) was the first antibiotic agent injected directly into the capsular bag as the final surgical step. This mode of delivery is considered superior to antibiotics added in the irrigating solution because the concentration achieved in the anterior chamber is much higher; furthermore, it is done at the end of the procedure, leaving a high dose in the anterior chamber for the early postoperative period. Considerable discussion occurred among clinicians and researchers about the safety and efficacy of intracameral injections until the large, multicenter, prospective, randomized, controlled European Society of Cataract and Refractive Surgeons (ESCRS) study showed intracameral cefuroxime (1 mg in 0.1 cc, first proposed by Montan et al.) to be effective in producing an 80% reduction in endophthalmitis rates. The global use of prophylactic intracameral antibiotics with cataract surgery has been steadily increasing since the ESCRS study. Dilution of cefuroxime remains a problem in the United States, but outside North America, prediluted cefuroxime is available from Thea (France) as Aprokam. However, cefuroxime does not cover multiresistant enterococci . A recent multicenter retrospective analysis of postoperative endophthalmitis in immediate sequential bilateral cataract surgery found intracameral vancomycin (1 mg in 0.1 mL) and moxifloxacin (100–500 µg in 0.1–0.2 mL) to be at least as effective as cefuroxime. Routine use of vancomycin is controversial because it is reserved as the last resort for multiresistant bacteria. The recent discovery of 36 cases of vancomycin-associated hemorrhagic occlusive retinal vasculitis has reduced surgeons’ enthusiasm about using prophylactic intracameral vancomycin. Intracameral moxifloxacin has theoretical benefits because of its potent bactericidal activity, availability as a self-preserved commercial formulation (Vigamox ^® ; Alcon Laboratories, Fort Worth, TX) requiring only very simple dilution, if any, and the fact that its mechanism of action differs from current antibiotics of choice for endophthalmitis, theoretically making any possible breakthrough endophthalmitis cases easily treatable. Its use is steadily increasing globally. Mounting evidence supports the use of intracameral antibiotics at the conclusion of surgery because they achieve supra-threshold antibiotic levels for an extended period.

Rapid miosis can be produced at the end of the surgical procedure by using intraocular parasympathomimetics acetylcholine chloride 1% or carbachol 0.01%. Current commercial preparations show no evidence of endothelial toxicity, and the choice of agent depends on the desired clinical features. Acetylcholine 1% has an onset of less than 1 minute with a relatively brief 10-minute duration of miosis, whereas carbachol 0.01% takes 2 minutes to act and lasts 2 to 24 hours. Both agents lower postoperative intraocular pressure spikes. Topical carbachol 0.2% is effective to induce 24-hour miosis and reduce postoperative IOP spikes but is no longer commercially available; therefore, pilocarpine 2% may be used, but its effect lasts only 8 hours, so the patient may be given the pilocarpine minim (in countries where minims are available; Bausch & Lomb) to reapply one drop at bedtime (personal observation – SAA).

Agents currently under investigation include low-molecular-weight heparin, enoxaparin (10 IU/mL added to standard irrigating solution), which produces a decreased inflammatory response immediately after cataract surgery with minimal side effects (e.g., hemorrhage). A preliminary study of ozonated water (4 parts per million [ppm] concentration) in anterior chamber irrigation confirmed its bactericidal effects, and this may potentially be another tool against endophthalmitis.

Irrigating Solutions

In the early days of phaco, the only irrigating solutions available were normal saline, Plasma-Lyte, and lactated Ringer’s solution. Their main adverse effect was endothelial cell toxicity. Irrigating solutions with calcium, glutathione, and bicarbonate form more physiologically balanced solutions ( Table 5.7.4 ). Several comparative studies found BSS Plus to be protective of the corneal endothelium and hence superior to BSS and other irrigating solutions. Unlike BSS, BSS Plus is physiologically similar to human aqueous and vitreous, especially with regard to calcium concentration and the addition of glucose, glutathione, and bicarbonate. BSS Plus maintains endothelial cell function over periods ranging from 15 minutes to in excess of a few hours. The buffer in BSS Plus is bicarbonate, which is an improvement over the sodium acetate and citrate buffers in BSS. Nevertheless, BSS Plus is currently used much less frequently compared with BSS because of cost and the progressive reduction in the volume of irrigating fluid used in surgery as techniques improve over time.

Corneal surface irrigation to maintain hydration and surgical clarity has traditionally been performed throughout intraocular procedures with BSS. The development of an elastoviscous Hylan Surgical Shield 0.45% (HSS), which decreases the surgeon’s dependence on manual corneal irrigation, is an improvement over BSS in maintaining corneal hydration and clarity intraoperatively. Some surgeons use a drop of ophthalmic viscosurgical device (OVD) on the cornea at the beginning of surgery to achieve prolonged wetting and reduced need for BSS irrigation with two newer topical OVDs specifically targeting this use: Visthesia (NaHa 0.3% + lidocaine 2%; Carl Zeiss Meditech) and Cornea Protect (HPMC 2%; Bausch & Lomb).