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Intraoperative use of intraocular pharmaceuticals may improve cataract surgery outcomes
Currently, two methods are used for intraoperative administration of pharmaceuticals.
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To have clinical efficacy, topical eye medications need to be formulated to adhere to the ocular surface and pass through the cornea and ocular tissues to achieve an adequate intraocular concentration of drug. But, if we can place these medications directly inside the eye during surgery, we have the ability to rapidly administer the desired dose.
Considerations
Pharmaceuticals that are injected or infused directly inside the eye must be safe, nontoxic, and both preservative- and bisulfite-free to avoid damage to delicate structures such as the corneal endothelium and the retina. This is different from medications that are given as periocular injections, either subconjunctivally or in the sub-Tenon’s layer, which can have preservatives.
Commonly used medications include anti-inflammatories such as ketorolac and triamcinolone, anti-VEGF agents such as bevacizumab, antibiotics including vancomycin and cefuroxime, and mydriatric agents such as phenylephrine and epinephrine. These drugs can have a beneficial effect during surgery or for postoperative recovery and quelling of inflammation.
A large study organized by the European Society of Cataract and Refractive Surgeons concluded that giving intracameral cefuroxime at the time of cataract surgery significantly reduced the rate of endophthalmitis. But when we compound and prepare drugs for off-label intraocular use, caution must be used to follow the exact recipe and achieve the proper dilution under sterile conditions. Otherwise, the risk of inducing toxic anterior segment syndrome or even endophthalmitis increases. In contrast, it is easier to use medications that are designed for intraocular use and come premixed and sterile.
Methods of delivery
Intraocular administration of drugs during surgery is localized to either the anterior segment or the vitreous cavity, depending on the desired target tissue.
Medication administered into the anterior chamber typically lasts hours because of the rapid turnover of aqueous every 90 to 120 minutes. This can be extended to a few days with injection of larger suspended particles, such as triamcinolone, which will adhere to the iris and other tissues and take longer to be washed out. Some surgeons advocate placing aliquots of medication within the capsular bag at the time of cataract surgery to prevent premature washout.
Figure 1. In a clinical trial of OMS302, which is a combination of ketorolac and phenylephrine designed for injection into the balanced salt solution infusion bottle during cataract surgery, patients receiving the product had significantly better maintenance of mydriasis, with just 1% of patients having a 50% reduction in operative field (pupil area) compared with 27% of patients receiving placebo.
Image: Devgan U
Injecting medications through the zonular apparatus or via the pars plana into the vitreous cavity will give a longer duration of action and a depot effect lasting many weeks. New time-release particles are being studied now to achieve months of therapy.
Instead of simply injecting medications into the eye during surgery, another option is adding these pharmaceuticals to the infusion bottle during cataract surgery. The advantage of a constant infusion of medication within the balanced salt solution is a prolonged pharmaceutical effect without washout during cataract surgery. This is often done with epinephrine and vancomycin, but new products are being investigated with more potential benefits. During a typical cataract surgery there is pupillary constriction as the procedure progresses, which reduces the operative field (the pupil area) and can make surgery more challenging.
Clinical results
Omeros has developed OMS302, which is a combination of ketorolac and phenylephrine that is designed to be injected into the balanced salt solution infusion bottle used in cataract surgery. The ketorolac is a potent NSAID, and the phenylephrine provides maximum pupil dilation for good access to the cataract. The potential clinical benefits are many, including better patient outcomes, fewer complications, improved visual recovery, safer and easier procedures, and the ability to manage higher-risk cases, such as intraoperative floppy iris syndrome.
In a recent clinical trial, patients receiving OMS302 had significantly better maintenance of mydriasis during cataract surgery. The results were dramatic, with just 1% of OMS302-treated patients having a 50% reduction of the operative field. This corresponded to about a 2.5-mm or more decrease in pupil diameter compared with 27% of placebo-treated patients (Figure 1). In addition, the patients who had the benefit of OMS302 had significantly less pain in the early postoperative period.
It seems natural to use this type of product for challenging cases such as small pupils, intraoperative floppy iris syndrome and in patients in whom more inflammation or pain is expected due to a complicated surgical situation. But, it may have an even greater role in routine cases in which the goal is to minimize surgical challenges like miosis, to avoid complications such as iatrogenic iris trauma, to address inflammation at the tissue site immediately as it develops, and to deliver a comfortable and pain-free experience to our patients.
Our goal for all of our cataract patients is simple: deliver a safe and gentle surgery with a quick recovery of excellent vision. Administering intraocular pharmaceutical agents at the time of surgery, either by direct injection or continuous infusion, can help our patients achieve the best outcomes.