The glaucoma literature suggests that compliance with topical drops is poor and decreases with the number of drops required.^1-3 While adherence to short-term, post-surgical drop regimens may be a bit better, cataract surgeons say complex dosing schedules impose a significant burden on patients and caregivers.

To reduce that burden, there is increasing interest among the cataract surgery community in treatment strategies that eliminate or significantly reduce the number of topical drops required postoperatively. These include intraoperative steroid injections (Dexycu, EyePoint Pharmaceuticals), compounded multidrug formulations for intravitreal or intracameral injection (Dropless formulations, ImprimisRx), continuous intraoperative ketorolac injections (Omidria, Omeros), and sustained-release intracanalicular steroid implants (Dextenza, Ocular Therapeutix).

A variety of minimally invasive glaucoma surgery (MIGS) procedures also offer the opportunity to address glaucoma at the time of cataract surgery, thereby reducing the need for topical IOP-lowering drops afterward.

In some cases, these drop-reducing strategies involve additional costs that may be passed on to the patient. In others, ambulatory surgery centers (ASCs) absorb the costs that would normally be borne by patients (or their insurers) when prescriptions are filled. Advocates believe the extra cost is worth it, for both safety and efficacy reasons.

Here, three cataract surgeons share the drop-free compounded regimens they have adopted for patients in their ASCs:

Approach #1: Completely Drop-Free

Since 2015, Lawrence Woodard, MD, of Omni Eye Center in Atlanta, has relied primarily on intraoperative injections of triamcinolone acetonide 15 mg/mL and moxifloxacin HCl 1 mg/mL (Tri-Moxi, ImprimisRx), given via trans-zonular injection, for control of infection and inflammation after cataract surgery (Figure 1).

“We had been growing increasingly frustrated by the difficulty of ensuring that patients got the right medication and the right dose,” Dr. Woodard says. With insurance formularies and generic substitution, he explained, it wasn’t unusual to find that a patient had been dispensed a generic QID drug instead of the prescribed QD drug—but had then followed the surgeon’s instructions to instill once daily, thereby getting only one-fourth the intended dose. Pharmacy call-backs were taking up more and more staff time. And Dr. Woodard learned firsthand, when his mother-in-law stayed with his family for a month after cataract surgery, how much patients disliked drop instillation.

“By moving to an intraocular approach, we are able to eliminate compliance concerns, make our patients’ lives easier, and better control the dose,” he says. Most patients in his practice use no drops before or after surgery at all. Those who are at high risk of developing cystoid macular edema (CME) are prescribed a non-steroidal anti-inflammatory (NSAID).

In one recent study of 1,166 eyes undergoing drop-free cataract surgery, only 9.1% required additional steroid drops after injections of transzonular Tri-Moxi, and there were no cases of endophthalmitis.⁴

Dr. Woodard believes that the bolus of steroid at the time of surgery prevents inflammation from getting started in most cases, and that careful postoperative monitoring can help surgeons avoid the occasional case of rebound iritis or CME that many worry will occur without an NSAID.

“What I have learned is that it is important to quickly address early warning signs. If I see any cells in the anterior chamber at 1 week, I put the patient on an NSAID,” he says. “This simple step has prevented symptomatic inflammation.” If the patient is already symptomatic, he starts an NSAID and a steroid.

From a business perspective, there have been unexpected benefits to the drop-free approach, Dr. Woodard says. “Our referring ODs love not having to go over the drop schedule [with patients], so they increased their referrals to us,” he notes. Additionally, the ASC has seen a reduction in surgery cancellations. “We discovered that patients were sometimes cancelling surgery due to sticker shock at the pharmacy when they went to pick up their preoperative drops,” he explains. “With a drop-free approach, we don’t see that happening as much.”

Approach #2: Drop-Free + NSAID

Kamran M. Riaz, MD, clinical associate professor at the Dean McGee Eye Institute at the University of Oklahoma in Oklahoma City, first turned to intraoperative injections to address what he calls the “4 Cs” of topical drops: Cost, Compliance, Collateral damage (in the form of ocular surface toxicity), and Calls from patients and pharmacies.

Dr. Riaz was an early adopter of Tri-Moxi-Vanc but says he switched to Tri-Moxi after reports that vancomycin was associated with hemorrhagic occlusive retinal vasculitis (HORV).⁵ No cases of HORV have been reported with the Tri-Moxi combination, which he injects into the vitreous cavity using a 30-gauge needle and a pars plana approach (Figure 2).

“We have found that intravitreal antibiotic-steroid is as effective as topical regimens at controlling anterior segment inflammation, but not as effective at preventing CME,”⁶ he says. For this reason, he also prescribes once-daily topical bromfenac 0.07% (Prolensa, Bausch + Lomb) or ketorolac. Those patients who are at very high risk for inflammation due to underlying conditions, such as diabetes, get a topical steroid as well.

“The biggest complication we’ve seen from the injection is that about three-quarters of patients notice floaters on post-op day 1,” says Dr. Riaz. “However, as long as you set expectations with patients about this in advance and tell them the floater is a sign of the medication doing its job, most are not bothered by it at all.”

Dr. Riaz says surgeons should remember that most of their prophylactic measures surrounding cataract surgery are off-label, and be open-minded about considering compounded injected medications, as long as they come from a reputable source.

“If you are going to inject a medication into the eye, it is important that it be from a compounding pharmacy with 503B designation, such as ImprimisRx or Leiters, to ensure quality control,” he says.

He also points out that injections at the time of cataract surgery are standard of care in many parts of the world, even though U.S. surgeons have continued to rely on topical drops.

“It’s easy to get stuck on ‘the way it’s always been done,’ but as the cost and burden of drops has increased, we should consider what is best for our patients,” Dr. Riaz says. “The cost to the ASC ends up being only about $24 per vial. Not only is it the right thing to do, but it quickly pays for itself in reduced staff time.”

The injection technique (see Haq et al.⁶ for a video demonstration) is easy to learn, he says: “Cataract surgeons absolutely should not consider the vitreous to be taboo.”

Approach #3: Drop-Free + Triple Drop

For those who want an NSAID on board but still want to minimize the number of drops, another approach is to combine an intraoperative injection with a combination once-daily drop after surgery.

Russell Swan, MD, of Vance Thompson Vision in Bozeman, MT, and adjunct assistant professor of ophthalmology at the University of Utah, says that is how his technique has evolved over time.

“For me, the driving force toward intraoperative injections was the antibiotic,” he says. “Endophthalmitis, while rare, is the most serious potential complication of cataract surgery. When you see a 7-fold reduction in that complication with intracameral moxifloxacin (Figure 1),⁷ I think you have to take that seriously.” He adds that the safety benefit makes it worth absorbing the small additional cost for the ASC.

Dr. Swan started with Tri-Moxi intravitreal injections, but wasn’t happy with the floaters associated with triamcinolone. He eventually settled on an intracameral injection of dexamethasone sodium phosphate 1 mg/mL / moxifloxacin HCl 0.5 mg/mL / ketorolac tromethamine 0.4 mg/mL (Dex-Moxi-Ketor, ImprimisRx). “Once surgery is complete and the wounds are sealed, I do an intracameral exchange of the anterior chamber volume with the injection,” he explains.

Inflammatory control is also important to him. “The published data from ESCRS and others^8,9 suggest that dual therapy (steroid + NSAID) results in at least a 2-fold reduction in CME compared to either type of anti-inflammatory alone,” he says (Figure 2). A combination triple drop—Dr. Swan relies on prednisolone 1% / moxifloxacin 0.5% / nepafenac 0.1%% (Pred-Moxi-Nepaf, LessDrops, ImprimisRx)—QD for 4 weeks is the simplest and most cost-effective regimen for patients.

“It has reduced [patients’] drop burden from 126 drops to 30 drops over the course of a month,” he says.

Although some colleagues are concerned about the risk of an IOP response to intracameral steroids, especially in glaucoma patients, Dr. Swan says he has found no difference in steroid response between patients on a topical regimen versus those with intraoperative steroids.¹⁰

The most important factor for him in the choice of compounded intraocular or topical formulations, Dr. Swan says, is that they be sourced from a 503B pharmacy.

“That designation provides a great deal of reassurance,” he says, “because it means there is potency, sterility, and endotoxin testing; stricter batch testing requirements; and regulatory oversight that you don’t get with 503A drugs.” ■

REFERENCES:

1. Stone JL, Robin AL, Novack GD, et al. An objective evaluation of eye drop instillation in patients with glaucoma. Arch Ophthalmol. 2009;127:732-736.
2. Hennessy AL, Katz J, Covert D, et al. Videotaped evaluation of eyedrop instillation in glaucoma patients with visual impairment or moderate to severe visual field loss. Ophthalmology. 2010;117:2345-2352.
3. Cate H, Bhattacharya D, Clark A, et al. Patterns of adherence behavior for patients with glaucoma. Eye. 2013;27:545-553.
4. Emara B. Dropless cataract surgery. American Society of Cataract and Refractive Surgery 2019 Annual Meeting, San Diego. May 5, 2019.
5. American Society of Cataract and Refractive Surgery. Clinical alert: HORV association with intraocular vancomycin. Ascrs.org/clinical-education/clinical-reports/2016-cr-clinical-alert-horv-association-with-intraocular-vancomycin . Last accessed June 3, 2020.
6. Haq Z, Zhang MH, Riaz KM. Short-term non-infectious outcomes after a pars plana intravitreal antibiotic-steroid injection of triamcinolone, moxifloxacin, and vancomycin during cataract surgery versus a standard postoperative topical regimen. Clin Ophth. 2020;14:1117-1125.
7. Haripriya A, Chang DF, Ravindran RD. Endophthalmitis reduction with intracameral moxifloxacin prophylaxis: Analysis of 600,000 surgeries. Ophthalmology. 2017;124(6):768-775.
8. Wielders LHP, Schouten JSAG, Winkens B, et al, ESCRS PREMED Study Group. European multicenter trial of the prevention of cystoid macular edema after cataract surgery in nondiabetics: ESCRS PREMED study report 1. J Cataract Refract Surg. 2018;44(4):429-439.
9. Hoffman RS, Braga-Mele R, Donaldson K, et al. Cataract surgery and nonsteroidal anti-inflammatory drugs. J Cataract Refract Surg. 2016;42:1368-1379.
10. Kindle T, Ferguson T, Ibach M, et al. Safety and efficacy of intravitreal injection of steroid and antibiotics in the setting of cataract surgery and trabecular microbypass stent. J Cataract Refract Surg. 2018;44(1):56-62.