As eye surgeons, one of the things that matters most to us is that patients use all their medications appropriately. However, despite best intentions, virtually no patient is 100% adherent to the therapeutic regimen. This applies to IOP-lowering drops for our glaucoma patients or postoperative medications following cataract surgery.

The reasons for this lack of compliance include the burden of regimen frequency and complexity, forgetfulness and physical dexterity — particularly in the elderly. Numerous studies show that not only do patients have difficulty successfully administering the correct number of drops, but they also often miss their eye.^1-6 This combination of factors naturally has a negative impact on the agents’ efficacy.

This means we have to engineer a way to take the matter of compliance out of patients’ hands as much as possible so we can truly dictate and control the medications they receive.

GLAUCOMA TREATMENT

A look at the medication burden

Simply put, if our glaucoma patients are not taking drops consistently or appropriately, they will not achieve the desired results — preserving vision. The drugs work, but if they do not get into the eye, they cannot be effective. On top of that, glaucoma drops are notorious for their side effects owing to preservatives such as benzalkonium chloride (BAK). Used in approximately 70% of ophthalmic formulations, BAK is well known to cause cytotoxic damage to conjunctival and corneal epithelial cells, resulting in signs and symptoms of ocular surface disease (OSD), such as ocular surface staining, increased tear break-up time and higher OSD symptom scores.⁷ Discoloration of the iris or skin around the eye is also a common complaint.

The MIGS option

Minimally invasive glaucoma surgery (MIGS) including laser, has transformed the glaucoma therapy landscape. Its safety and efficacy have allowed us to be much more interventional in our approach to managing glaucoma.

For my patients who have a new diagnosis of glaucoma and have never been on drops, often I elect to perform selective laser trabeculoplasty (SLT) as first-line therapy as opposed to prescribing a prostaglandin agent. Results from the LiGHT trial support this, finding that SLT provided more robust IOP lowering while being a more cost-efficient first-line treatment when compared to drops.⁸

Coming from an interventional mindset, I have more control over the IOP-lowering effect that can be achieved. If patients do not reach the target pressure, I can always add medications. I think minimally invasive surgery first, medication second when it comes to glaucoma management.

Sustained-release

Another advance I have been using for about a year is the recently-approved sustained-release 10-mcg bimatoprost implant. Intracameral, biodegradable Durysta (Allergan) is indicated to reduce IOP in patients with open-angle glaucoma or ocular hypertension. The spongy capsule is simple and quick to implant in the anterior chamber where it slowly releases bimatoprost over the course of months and, in my experience, sometimes as long as a year.

My patients have responded very well to the implant, with many not having to go back to their prostaglandin analogue drop for a year. Drug elution is the next generation of medication reduction.

Back to the drawing board with drops

When drops are necessary, I make sure to counsel patients and their caretakers and take the time to let them know how glaucoma works. When patients are not in pain and have no vision issues, it can be difficult to convince them to stick to a regimen, especially one that is costly, has side effects and must be done on a daily basis. I may be the first to explain the process to them.

I let patients and their caretakers know that, although they may be seeing well now, glaucoma is progressive and will affect their peripheral vision if not well controlled. I say, “It takes away more and more until eventually you are left with tunnel vision. That is why it is imperative you stick to this medication regimen.”

I tell them that glaucoma is the silent thief of vision, explaining that, “I’m not trying to scare you, but I want you to know that using this drop daily is what’s going to keep you from going blind.” These phrases have been very helpful in encouraging their adherence.

CATARACT SURGERY

Postop conundrums

Drop regimens after cataract surgery are notoriously cumbersome. In the past when I prescribed three agents — a nonsteroidal anti-inflammatory drug (NSAID), steroid and antibiotic — patients would frequently come to their follow-up appointment with the wrong caps on the bottles. They might be using the NSAID four times a day instead of the steroid or vice versa.

In a cataract patient with glaucoma, the scenarios are even worse: imagine six bottles of drops. Frankly, it is unsafe.

Accompanying patients’ rampant confusion regarding the three-drop regimen was the endless callbacks. As a high-volume center, we perform more than 5,000 cataract procedures a year. The amount of time my call center and other team members spent talking to patients about their drops was staggering. Also, patients would be frustrated by the cost of their medications. Often, they would think we were “in on it” and that we were getting “a cut.” We had to explain to patients that we have no control over what the insurance company or the pharmacy charges.

From three bottles to one

Five years ago, we took a step back to figure out how to change this situation. The first thing I did was incorporate intracameral medications and reduced the drop burden down to a single bottle. This was achieved by using the so-called “dropless” and “less drops” strategies first commercialized in 2014 by ImprimisRx, a pharmaceutical compounding business that is a wholly owned subsidiary of Harrow Health, Inc. The three-in-one injection Dex-Moxi-Ketor consists of dexamethasone 1 mg, moxifloxacin 0.5 mg and ketorolac 0.4mg/mL. Additionally, we prescribe the company’s three-in-one drop Pred-Moxi-Nepaf — prednisolone acetate 1%, moxifloxacin 0.5% and nepafenac 0.1% — twice daily.

So, my regimen, which was once three different drops prescribed for a total of sometimes 12 times a day costing hundreds of dollars, now consists of one bottle twice a day. My instruction is simple: Instill these drops twice a day starting the day after surgery until the bottle is empty. Patients usually get 3 weeks of drops for each eye from one bottle.

This approach has been very successful: I have not seen an increase in cases of worsening cystoid macular edema or inflammation with the new approach compared to the traditional strategy. Call backs with concerns around postoperative cataract drops have reduced an estimated 90%. Using only one bottle is extremely easy for patients and has improved compliance dramatically — plus it is cheaper. Drops can sometimes cost patients more than $400; the three-in-one drop is around $80.

ImprimisRx having FDA’s 503B certification status as an outsourcing facility has been instrumental in allowing us to bring these medications in-house. Patients no longer need to go to the pharmacy and there is no mystery around cost; more than 90% of my patients elect to use the option. OSRX Pharmaceuticals is another supplier of combination formulations.

CONCLUSION

Generally speaking, patient adherence to using eyedrops is poor, with studies suggesting an overall nonadherence rate of about 30%. However, it is likely much higher.⁹ A recently conducted literature review of medication adherence after cataract surgery found that the problem of patient nonadherence in this setting may be more profound.¹⁰

Certainly, the patient population is more likely to have difficulties instilling eyedrops, including problems with manual dexterity, tremor, difficulty tilting the head back, visual impairment and conditions that affect hand strength and the ability to open and squeeze a bottle.^4,11 Compounding the problem, older patients may have cognitive or memory problems that make it less likely they can adhere to a drop schedule.

By employing alternative strategies to drop regimens, we can both alleviate the burden they put on patients and also gain more control over visual outcomes. OM

REFERENCES

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3. An JA, Kasner O, Samek DA, Levesque V. Evaluation of eye drop administration by inexperienced patients after cataract surgery. J Cataract Refract Surg. 2014; 40:1857-1861.
4. Dietlein TS, Jordan JF, Luke C, et al. Self-application of single-use eyedrop containers in an elderly population: comparisons with standard eyedrop bottle and with younger patients. Acta Ophthalmol. 2008; 86:856-859.
5. Newman-Casey PA, Robin AL, Blachley T, et al. The most common barriers to glaucoma medication adherence: a cross-sectional survey. Ophthalmology. 2015;122:1308-1316.
6. Renfro L, Snow JS. Ocular effects of topical and systemic steroids. Dermatol Clin. 1992;10:505-512.
7. Goldstein MH, Silva FQ, Blender N. Ocular benzalkonium chloride exposure: problems and solutions. Eye (Lond). 2021;14:1-8.
8. Gazzard G, Konstantakopoulou E, Garway-Heath D, et al. Selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma (LiGHT): a multicentre randomised controlled trial. Lancet. 2019;393:1505-1516.
9. Vandenbroeck S, De Geest S, Dobbels F, et al. Prevalence and correlates of self-reported nonadherence with eye drop treatment: the Belgian Compliance Study in Ophthalmology (BCSO). J Glaucoma. 2010;20:414-421.
10. Matossian C. Noncompliance with prescribed eyedrop regimens among patients undergoing cataract surgery—prevalence, consequences, and solutions. US Ophthalmic Review. 2020;13:18-22.
11. Connor AJ, Severn PS. Force requirements in topical medicine use — the squeezability factor. Eye (Lond). 2011;25:466-469.

Blake K. Williamson, MD, MPH, MS, is a refractive and anterior segment surgeon at Williamson Eye Center, Baton Rouge, Louisiana. Email him at blakewilliamson@weceye.com. Dr Williamson is a consultant to Glaukos, ImprimisRx, New World Medical and SightSciences.