EyeWorld is the official news magazine of the American Society of Cataract & Refractive Surgery.
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To claim CME credit and view expanded content, go to www.CMESupplement.eyeworld.org Understanding surgical stress and the inflammatory cascade by Clara C. Chan, MD S urgical stress begins prior to incisions and is influenced by many factors during surgery, some of which are beyond the surgeon's control. This stress triggers a cascade of metabolic events that results in increased inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids act at different and synergistic parts of the inflammatory cascade, thus they can be effective when used in combination. Sources of surgical stress There are three sources of surgical stress: the incision, epithelial trauma, and endothelium loss. Epithelial trauma is caused by dilation and anesthetic drops and the povidone iodine preparation. Additionally, there is endothelium loss. There is more endothelial cell loss if the axial length is shorter or if the phaco time is longer. The type of incision (scleral tunnel or clear corneal incisions) also plays a role in the amount of endothelium loss. Whenever ultrasound energy is used, there is the potential for wound burn. My colleagues and I published a study to determine the risk factors for wound burn.1 We found that the risk of wound burn decreased 45% with a doubling of surgical volume. Additionally, exothermic viscosurgical devices (dispersive viscoelastics) seem to create more heat production than the cohesive forms. Phaco techniques also play a role. Divide-and-conquer takes more time and uses more energy than chopping techniques. Therefore, the risk of wound burn with divide-and-conquer is higher. Risk was not found to be related to the machine used. Foreign substances also have an effect. For example, povidone iodine is toxic if it inadvertently enters the anterior chamber. Toxic anterior segment syndrome has been reported with the use of the generic form of trypan blue. Intracameral antibiotics can also cause surgical stress, if there is dilution error or the wrong pH level. This has been reported with the intracameral use of both cefuroxime and vancomycin. Surgical difficulties—dense nucleus, broken capsule, retained nucleus or cortex, iris turbulence and trauma, floppy iris syndrome or zonular damage, intraoperative miosis—can also cause surgical stress. The inflammatory cascade Certainly, prostaglandins are the biggest mediator. They have been shown to increase leukocyte migration, pain stimulation, miosis, vasodilation, vascular permeability, and disruption of the blood-aqueous barrier causing increased cell and flare reaction. There are two strategies to avoid the synthesis and release of pro-inflammatory mediators: use steroids to stop it Demonstration of how corticosteroids and NSAIDs can inhibit different parts of the inflammatory cascade early in the cascade and use NSAIDs to stop it later in the cascade. Steroids inhibit phospholipase A2 early on in the inflammatory cascade to prevent the release of arachidonic acid from cell membrane phospholipids. Later in the cascade, NSAIDs can act on the cyclooxygenase pathway (COX-1 and COX-2) to inhibit conversion of arachidonic acid to prostaglandins. Certainly, a comprehensive strategy is better than just a single tactic. Because NSAIDs and corticosteroids act at different and synergistic parts of the inflam- matory cascade, they can be very effective when used in combination. Reference 1. Sorensen T, Chan CC, Bradley M, Braga-Mele R, Olson RJ. Ultrasound-induced corneal incision contracture survey in the United States and Canada. J Cataract Refract Surg. 2012;38(2):227-233. Dr. Chan is from the Department of Ophthalmology and Vision Sciences, University of Toronto. She can be contacted at clarachanmd@gmail.com. Perioperative strategies to prevent inflammation by David A. Goldman, MD A ny inflammation reduces patient satisfaction, so our goal should be to eliminate, not just reduce, inflammatory side effects of cataract surgery. We need to use the most potent therapies available and adapt a regimen to encourage compliance. Surgeons need a multi-pronged strategy that starts with preoperative prevention. This includes the use of topical nonsteroidal anti-inflammatory drugs (NSAIDs) in high-risk cases and pulsed topical corticosteroids on the day of surgery. It is also important to use a surgical technique that minimizes trauma and a postoperative regimen that maximizes patient compliance and outcomes. Medication strategies I only use NSAIDs before the day of surgery and only in high-risk patients. They are valuable if they prevent miosis and allow surgeons to avoid iris hooks. They are also useful in cases where there is a high risk for inflammation. However, I typically don't use NSAIDs preoperatively for routine cataract surgery because most patients are only willing to use one bot- tle of medication, and I would rather that they extend the NSAID therapy postoperatively. I do not use steroids or antibiotics preoperatively. Steroid use without antibiotics can increase bacterial overgrowth on the ocular surface, and antibiotic use can select for resistant strains preoperatively. My regimen On the day of surgery, patients receive NSAIDs in the preoperative area. Patients receive one drop of difluprednate in the operating room at the end of the case and another drop in the recovery area. I then instruct them to instill another drop when they get home. This pulsed dose helps their eyes to be clear and comfortable by dinner time. Postoperatively, patients use difluprednate once a day in the morning and nepafenac once a day in the evening. If patients have corneal edema on postoperative day one, I give them an extra drop of difluprednate in the clinic. Typical postoperative regimens include a tapering dose of steroids over several weeks and an NSAID regimen until the bottle is gone. Patients appreciate the ease of my regimen because it is one drop in the morning and one drop in the evening for the entire course of treatment. I think all patients benefit from a less frequent dosing regimen. They can leave their drops at home and not be concerned about it during the day. There are advantages and disadvantages to all of the currently available steroids. However, only difluprednate and loteprednol are available as emulsions. Steroids that are available as suspensions must be shaken before use, and studies have shown that, even when shaking the drops, the dose is variable. Some doses are 50% of the label claim, while other doses are 200% of the label claim. In contrast, an emulsion will have the same amount of medication every time. All NSAIDs can have corneal toxicity. One of the biggest concerns with NSAIDs is keratitis, and this may be due to the analgesic effect that the NSAID has on the ocular surface. I prefer to dose the NSAID in the evening before patients go to sleep so that their eyes are closed after instillation. The advantage of using both a steroid and an NSAID is the synergistic effect on the inflammatory pathway. Because of this synergistic effect, we are able to use less of each medication, reducing the chance of an IOP spike and keratitis, respectively. Additionally, steroids and NSAIDs are more effective than steroids alone in preventing CME, and preventing CME is much better than treating CME in terms of visual outcomes. Surgical technique Surgical technique is also important. We want to minimize phaco energy. We want to try to keep the phaco tip away from the endothelium as much as possible because it's not just how much energy is used but where it is being used. If a patient has endothelial compromise, a soft-shell technique is very effective, and it is important to make sure to remove all of the lens material. Dr. Goldman is in private practice, Palm Beach Gardens, Fla. He can be contacted at david@goldmaneye.com. Copyright 2013 ASCRS Ophthalmic Corporation. All rights reserved. The views expressed here do not necessarily reflect those of the editor, editorial board, or the publisher, and in no way imply endorsement by EyeWorld or ASCRS.