Challenges to topical drop adherence after cataract surgery

Special to Ophthalmology Times®

In general, patient adherence to using eye drops is poor, with studies suggesting an overall nonadherence rate of about 30%.¹

Patients’ belief in the utility of the eye drop, remembering to use it regularly, cost, and access to medication are concerns across a variety of disease states.

However, most of what is known about drop adherence has been learned in the context of chronic topical therapy for glaucoma.

Related: (AAO) Study outlines use of injectable intraocular steroid over drops

I recently conducted a review of the literature on medication adherence after cataract surgery and found that the problem of patient nonadherence in this context may be more substantial, albeit unintentional.² 

In part, this is because patients undergoing cataract surgery are typically in the age group most likely to have difficulties in instilling eye drops, 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.^3,4

Older patients also may have cognitive or memory problems that impair their ability to adhere to a drop schedule.

In a prospective Canadian study in which patients who had cataract surgery were video-recorded instilling their drops on postoperative day 1, only 7% of the 54 patients did everything right.

Most patients missed their eye completely (31.5%), instilled the wrong number of drops (31.5%), failed to wash their hands (77.8%), and/or contaminated the bottle tip (57.4%).⁵

A complex regimen
Odds are against success when it comes to eye drops in the cataract surgery population, thanks to the complexity of the regimen. We typically prescribe an antibiotic, a steroid, and a nonsteroidal anti-inflammatory drug (NSAID), each of which has a different instilling schedule.

Related: Drug delivery vs drops: Controlling postop pain, inflammation in cataract surgery patients


Patients may also be using drops for pre-existing conditions, such as glaucoma or dry eye. They (or their caregivers) may be instilling up to 14 drops per day from 4 or more bottles following the first eye surgery, and then a different schedule for the second eye a few weeks later.

The confusion can be compounded when, because of insurance restrictions, the pharmacy fills a prescription for a branded qd topical NSAID with a tid or qid generic substitution, necessitating major changes in the drop schedule instructions.

If patients followed our instructions to wait 15 minutes between drops to avoid washout (they do not), their entire day could revolve around drop schedules. This is burdensome for patients and their family members or caregivers.

Even when they do instill the drops on schedule, there is the challenge of getting a topically applied drug to the target tissue inside the eye.

In addition to the problem of the drops landing on the lids, cheek, or lashes, physiological barriers including reflex tearing and the tight junctions of the corneal epithelium mean that only 1% to 7% of the instilled drug reaches the aqueous humor.⁶

With steroid drops, patients often fail to vigorously shake the bottle long enough to achieve a homogenized suspension of the active ingredient.

This can lead to the patient getting mostly vehicle and very little drug during the initial weeks after surgery, and too much drug later in the course of therapy.

Related: Teleretinal screening fails to do double duty for detecting glaucoma, cataracts


Fixing the problem
Increasingly, I have become convinced that wherever possible, we should move away from topical regimens following cataract surgery.

The consequences of missed or incorrectly instilled doses can range from mild corneal edema, discomfort, and slower visual recovery to an increased risk of corneal abrasions, cystoid macular edema, and endophthalmitis.

Through a combination of sustained-release technologies and compounded medications, it is possible to eliminate some or all postoperative drops.

For surgeons who have not used any of these options, I would encourage my colleagues to first consider how comfortable they are with compounded medications vs FDA-approved drugs.

Although compounded injections and topical drops are legal, some clinicians or facilities are less comfortable using them.

Related: Minimize inflammation after cataract surgery

Next, I would suggest replacing 1 topical therapy at a time. The prime candidate for elimination is the topical steroid because it contributes the greatest complexity to the regimen, with a long duration of use that is complicated by a tapered instilling schedule and, often, the requirement to shake the bottle.

We now have compounded steroid injections or combination drops from ImprimisRx and Ocular Science, and 2 FDA-approved sustained-release dexamethasone products (Dexycu, EyePoint Pharmaceuticals, and Dextenza, Ocular Therapeutix) to reduce the adherence burden on patients and give surgeons more control over delivery of the steroid.

Dexycu is a biodegradable, extended-release formulation of dexamethasone 9% that is injected into the ciliary sulcus or into the capsular bag at the end of cataract surgery, where it delivers a tapering dose of steroid for the first few weeks after surgery.

In a randomized, controlled clinical trial, complete anterior chamber cell clearing was achieved in 60% of the Dexycu eyes versus 20% in the placebo group at postoperative day 8.⁷

Dextenza is a bioerodible 0.4-mg dexamethasone insert that can be placed in the lower canaliculus before, during, or after cataract surgery, where it releases steroid onto the ocular surface for 30 days.

In clinical trials, it resulted in less pain and inflammation than a placebo insert.⁸ Patients greatly prefer these sustained-release options over topical steroid drops.^9,10

Both are FDA approved and have pass-through status, so their cost is typically covered by Medicare or private insurance.

Related: Improving surgical safety, efficiency, and outcomes for patients

Intracameral dexamethasone has the advantage of being applied much closer to the target tissue than topical or intracanalicular options. It does not have to cross the corneal and conjunctival barriers; instead, the surgeon places it under the iris and near the ciliary body, where the inflammatory cascade begins.

When I participated in the Dexycu clinical trials, I noticed how quiet the anterior chambers appeared postoperatively, with hardly any cell or flare on postoperative day 1. I attribute this to not only the site of injection, but also the timing.

With topical drops, although we instruct the patient to instill the steroid 4 times a day starting several hours after surgery or starting the next morning if the eye is patched at the time of surgery, the reality is that family members may still need to make a trip to the pharmacy, or the patient may go home and fall asleep before instilling the drops.

It can be from 12 to 24 hours or more before the first dose of topical steroid is delivered to the eye, compared with just a few seconds when the surgeon injects Dexycu at the conclusion of the case.

Related: Changing patient conversations around cataract surgery

There is a bit of a learning curve for the proper injection technique for Dexycu; there is also the possibility of migration of the dexamethasone spherule onto the IOL optic or onto the iris, where it becomes visible until its absorption within a few days.

With intraoperative sustained-release steroids—perhaps coupled with other injected or sustained-release drugs—we can eliminate the gambles of patient adherence.

This has the potential to greatly enhance the patient experience, improve practice flow, and provide the surgeon with more control over unwanted postoperative complications.

Read more by Dr. Matossian

About the author
Cynthia Matossian, MD, FACS, ABES
e:cmatossian@cmassociatesllc.net
Matossian is the founder and medical director of Matossian Eye Associates, an integrated ophthalmology and optometry group practice with 3 offices in Pennsylvania and New Jersey. Matossian Eye is an affiliate of Prism Vision Group. She also serves as a clinical instructor in the Department of Ophthalmology at Temple University Lewis Katz School of Medicine. Matossian is a consultant to Allergan, Bausch + Lomb, ImprimisRx, Shire/Novartis, and Sun Pharmaceuticals.

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References
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2. Matossian C. Noncompliance with prescribed eyedrop regimens among patients undergoing cataract surgery—prevalence, consequences, and solutions. US Ophthalmic Review. 2020;13(1):18-22. doi:10.17925/USOR.2020.13.1.18

3. Dietlein TS, Jordan JF, Lüke 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(8):856-859. doi:10.1111/j.1755-3768.2007.01155.x

4. Connor AJ, Severn PS. Force requirements in topical medicine use—the squeezability factor. Eye (Lond). 2011;25(4):466-469. doi:10.1038/eye.2011.5

5. An JA, Kasner O, Samek DA, Levesque V. Evaluation of eyedrop administration by inexperienced patients after cataract surgery. J Cataract Refract Surg. 2014;40(11):1857-1861. doi:10.1016/j.jcrs.2014.02.037

6. Ghate D, Edelhauser HF. Ocular drug delivery. Expert Opin Drug Deliv. 2006;3(2):275-287. doi:10.1517/17425247.3.2.275

7. Donnenfeld E, Holland E. Dexamethasone intracameral drug-delivery suspension for inflammation associated with cataract surgery: a randomized, placebo-controlled, phase III trial. Ophthalmology. 2018;125(6):799-806. doi:10.1016/j.ophtha.2017.12.029

8. Walters T, Bafna S, Vold S, et al. Efficacy and safety of sustained release dexamethasone for the treatment of ocular pain and inflammation after cataract surgery: results from two phase 3 studies. J Clin Exp Ophthalmol. 2016;7:4. doi:10.4172/2155-9570.1000572

9. Donnenfeld ED, Solomon KD, Matossian C. Safety of IBI-10090 for inflammation associated with cataract surgery: phase 3 multicenter study. J Cataract Refract Surg. 2018;44(10):1236-1246. doi:10.1016/j.jcrs.2018.07.015

10. Gira JP, Sampson R, Silverstein SM, et al. Evaluating the patient experience after implantation of a 0.4 mg sustained release dexamethasone intracanalicular insert (Dextenza): results of a qualitative study. Patient Prefer Adherence. 2017;11:487-494. doi:10.2147/PPA.S126283