In this episode of Interventional Mindset, Eric Donnenfeld, MD, and John Hovanesian, MD, discuss three ways drug delivery in cataract surgery can be optimized with new therapies and devices while offering clinical pearls for performing dropless cataract surgery.
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The shift to dropless cataract surgery via improved drug delivery
Taking control of your patient’s medications is the second most important factor to treatment success in cataract surgery after the actual procedure, began Dr. Donnenfeld. Dr. Hovanesian agreed, noting that, for patients, the procedure is only 5 to 10 minutes (wherein they are asleep), but the part that is most memorable to them is the before and after care—including the number of drops they take for the weeks following the procedure.
Topical treatments post-cataract surgery are full of pitfalls, with compliance being the foremost, as around 30 to 93% of patients fail to comply in some way with their drop regimen.1,2 This is largely due to physical limitations that may inhibit patients from adequately instilling a drop into the eye.
Further, a study by Vandenbroeck et al. demonstrated that almost 40% of patients struggle with nonadherence to eye drop treatments.3 There is nothing more frustrating than performing a perfect surgery and then having the patient’s visual results go awry due to compliance issues, emphasized Dr. Donnenfeld.
He then listed the 5 Cs for how optimized drug delivery can potentially improve cataract surgery:
- Compliance: Patients are more likely to comply because more of the treatment is in the hands of the clinician.
- Cornea: Topical drops have preservatives that can cause dry eye and toxicity.
- Comfort: Similarly, drops can cause stinging, which may demotivate patients from continuing to use the drops.
- Cost: Many of the post-operative drops are expensive, which creates financial barriers to patients receiving the care they need.
- Cosmesis: Topical drops can cause red eye and irritation, which can impact the patient’s cosmesis, and it can be particularly difficult for patients who wear makeup as the drops can cause smearing.
Dr. Hovanesian added a sixth C, control, reiterating the importance of putting as much control of the treatment in the clinician’s hands to ensure a higher probability of successful treatment outcomes.
How drug delivery in cataract surgery can be improved
The doctors then switched to discussing the three areas where improved drug delivery in cataract surgery could optimize treatment outcomes via prevention of infection, reduced inflammation, and prevention of cystoid macular edema (CME).
1. Preventing infection after cataract surgery
While topical antibiotics have been the standard of care to prevent infection following cataract surgery for a long time, there is data that has demonstrated the benefit of injecting antibiotics directly into the eye, explained Dr. Hovanesian.
Intracameral antibiotics are starting to become more of a standard of care in the US, although roughly less than half of American surgeons use them during cataract surgery.4 The most common medication used for intracameral antibiotics is moxifloxacin, followed by cefuroxime and vancomycin. Of the three, moxifloxacin tends to have the broadest spectrum coverage, does not use preservatives, is widely available, and has low toxicity.4
Dr. Donnenfeld noted that he leverages intracameral antibiotics in all of his cataract surgery patients as his go-to, however, occasionally, he supplements this with topical antibiotics. Specifically, if he is performing fairly large limbal relaxing incisions (LRIs) or making incisions into the eye (i.e. larger clear corneal incisions, scleral tunnels with or without sutures), he prefers to coat the ocular surface with antibiotics as well.
Studies supporting the use of intracameral moxifloxacin
Most American surgeons have gravitated toward intracameral moxifloxacin, observed Drs. Hovanesian and Donnenfeld, and findings from studies have illustrated that rates of endophthalmitis are very low. For example, one study measured the rates of posterior capsule rupture (PCR) and post-operative endophthalmitis (POE) in 10 Aravind Eye hospitals in India, showing that with intracameral moxifloxacin, the rate of POE was 2 per 10,000.5
Additionally, a study by Shorstein et al. found intracameral moxifloxacin could be used successfully without topical drops.6 They demonstrated that adopting intracameral antibiotic injection correlated with a decline in the rate of POE, and a lower infection rate was reported with intracameral injection alone.
Of note, in Europe, topical antibiotic prophylaxis has almost completely disappeared. Intraocular delivery of antibiotics has become universal practice in Sweden, is deemed the standard of care in France and Denmark, and is recommended by national societies in several countries.2
2. Anti-inflammatory treatments in cataract surgery
Similar to topical antibiotics, prednisone acetate was the standard of care for anti-inflammatory treatments. Now a commonly used drug delivery system for steroidal anti-inflammatory medication is a preservative-free intracanalicular insert that can be placed in the punctum at the time of surgery, called Dextenza (dexamethasone ophthalmic insert 0.4mg, Ocular Therapeutix).
Dextenza is FDA-approved with an indication for both 1) the treatment of ocular inflammation and pain following ophthalmic surgery and 2) ocular itching associated with allergic conjunctivitis.7 The process is similar to inserting a temporary collagen punctal plug, as it is made of hydrogel material that dissolves and releases the dexamethasone in a tapered dose in the punctum for up to 30 days.
Over time, Dextenza resorbs and exits the nasolacrimal system without the need for surgical intervention. With its low-dose steroid formula, it may help to treat post-operative dry eye by acting as a punctal plug that bathes the cornea with topical dexamethasone to possibly prevent a heightened inflammatory response.
Subconjunctival triamcinolone acetonide
However, Dextenza can be expensive for patients when insurance coverage is challenged or denied, so a potential alternative could be subconjunctival triamcinolone acetonide, mentioned Dr. Donnenfeld. For doctors with patients who might not be a good fit for a canalicular insert, subconjunctival triamcinolone is a straightforward and inexpensive alternative.
The second report from the PREvention of Macular EDema after cataract surgery (PREMED) study from the European Society of Cataract and Refractive Surgeons (ESCRS) found that perioperative 40mg subconjunctival triamcinolone acetonide could dramatically reduce the risk of CME in diabetic patients undergoing cataract surgery.8
In fact, patients who received a subconjunctival injection of triamcinolone acetonide towards the end of cataract surgery had both a lower macular thickness and macular volume at 6 and 12 weeks post-operatively.
Consequently, for all of his diabetic patients, Dr. Donnenfeld recommends subconjunctival triamcinolone acetonide. While the recommended dose is 40mg, for a routine cataract surgery, Dr. Donnenfeld prefers to use around 10mg of triamcinolone.
Dr. Hovanesian added that both of these alternatives provide tapering doses, and the taper for topical therapies is only as good as the patient’s adherence to follow the drop regimen and the ability of the vial to provide a consistently tapering dose, which is not always possible with a suspension formulation, such as in prednisone acetate.
3. Preventing CME after cataract surgery
The first report from the PREMED study compared the efficacy of topical corticosteroids (dexamethasone 0.1%), non-steroidal anti-inflammatory drugs (NSAIDs, bromfenac 0.09%), and a combination of both following cataract surgery to prevent the occurrence of CME in nondiabetic patients.9 The findings demonstrated that bromfenac 0.09% twice daily for 2 weeks was more effective than dexamethasone 0.1% four times daily with one drop less per day every following week.
Dr. Donnenfeld explained that in the past, doctors relied on ketorolac tromethamine 0.4% ophthalmic solution QID, with patient reports of irritation and burning upon instillation of the drops. However, topical bromfenac has become a helpful alternative and can be used once a day, which he finds to be similarly effective.
Intracameral OMIDRIA for intra-operative mydriasis and CME prevention
Additional alternatives in the form of intracameral NSAIDs now exist as well. In particular, both Drs. Donnenfeld and Hovanesian recommended intracameral OMIDRIA (phenylepinephrine and ketorolac intraocular solution 1% / 0.3%, Rayner Surgical).
OMIDRIA is a sterile solution in which ketorolac is placed in a balanced salt solution (BSS) with phenylepinephrine to maintain mydriasis during surgery by preventing intra-operative miosis and potentially reducing post-operative pain.10 Currently, OMIDRIA is in an ongoing clinical trial to investigate whether intracameral OMIDRIA can deliver appropriate therapeutic levels of ketorolac into the vitreous to provide a sustained release of NSAIDs at the time of surgery.11
Dr. Donnenfeld highlighted a prospective study that he will present at ASCRS, comparing the levels of ketorolac in patients undergoing combined cataract surgery and vitrectomy (usually in patients with cataracts and epiretinal membranes), who were prescribed either topical ketorolac QID for 3 days or intracameral OMIDRIA. Initial analyses have indicated that trace levels of ketorolac are around five times higher with the use of OMIDRIA than with topical drops.12
These results support the clinical findings that patients who undergo cataract surgery with intracameral OMIDRIA have “white, quiet eyes with a lower risk of CME,” explained Dr. Donnenfeld.
Nepafenac and IOL attachment
Dr. Donnefeld mentioned an additional study published in the Journal of Cataract and Refractive Surgery (JCRS) on the safety and efficacy of a nepafenac punctal plug delivery system that resulted in significantly more pain-free patients, reduced inflammation, and better vision.13 Of note, the plug retention rate was 98% at Day 14 post-operatively.
Finally, Dr. Hovanesian brought up OcuRing (ketorolac ophthalmic implant, LayerBio), which is a bioerodible sustained-release ketorolac implant that can be applied to the haptic of an intraocular lens (IOL) during cataract surgery.14
Comparing drug delivery systems to a topical regimen after cataract surgery
Drs. Donnenfeld and Hovanesian recently published a paper together comparing three dropless drug delivery systems to conventional topical therapy in cataract surgery.15
Patients with bilateral cataracts were randomized to receive either intracanalicular dexamethasone insert (Dextenza), intracameral phenylephrine 1% / ketorolac 0.3% (OMIDRIA), and intracameral moxifloxacin 50μg in the study group while the control group consisted of topical moxifloxacin 0.5%, ketorolac 0.5%, and prednisolone acetate 1.0% QID.
They found that there was no CME in any of the 30 patients (60 eyes), and there were similar scoring of ocular inflammation and pain levels. However, what differentiated the two most significantly was both cost and patient preference. Nearly all of the patients greatly favored the dropless regimen (94.7%).15
Conclusion
Both Drs. Donnenfeld and Hovanesian agreed that improved drug delivery is the future of cataract surgery, and interested surgeons can make the change today by either reducing the number of drops utilized after cataract surgery or fully switching to a dropless regimen.
With a range of options, such as intracameral moxifloxacin, Dextenza, intracameral OMIDRIA, nepafenac punctal plug, and more, there is a significant opportunity to take an interventional mindset by treating cataract surgery patients with either a low dose or no dose of topical drops to potentially improve treatment outcomes and overall patient care.
