What’s new in contemporary ophthalmic drug delivery systems

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Georg Ebers in 1872 discovered Egyptian formulas with copper and manganese that had anti-infective properties.¹ Since then, a lot has changed in the ways of medical practice. In 2024, there is an increasing need for better ophthalmic drugs utilizing optimal drug delivery systems. Contemporary challenges for new ophthalmic drugs and drug delivery systems are frequency of administration, adherence, duration, and ineffective intraocular bioavailability at the target tissue. In situ gels, ocular implants, and nanoparticles constitute modern formulations often used in clinical practice. Furthermore, the use of preservatives in ophthalmic drug vehicles can cause adverse effects as described by the National Eye Institute (NEI), National Institutes of Health (NIH), in the early 1970s.²

One very important and growing theme of ophthalmic drug delivery systems is the move toward preservative-free drug delivery systems. When prescribing all types of ophthalmic drugs including OTC products, it is increasingly important that optometrists understand the nuances of contemporary ophthalmic drug delivery systems to provide better care for our patients. This article will concentrate mostly on topical ophthalmic drug delivery systems that are vital for every clinical optometrist’s toolbox. Additionally, I will briefly mention new injectables and implantable drug delivery systems that have been approved since 2023.

Innovations in the treatment of dry eye

Let’s review recent FDA approvals for ophthalmic drugs approved for the treatment of the signs and symptoms of dry eye disease (DED):

A collaboration between Bausch + Lomb and Novaliq, Miebo (perfluorohexyloctane ophthalmic solution; formerly NOV03) was designed to significantly reduce tear evaporation.³ It is a preservative-free drug to be applied 4 times a day to each eye. It is the only FDA-approved drug for DED that was specifically designed to reduce tear evaporation.³

Novaliq’s Vevye (cyclosporine ophthalmic solution) 0.1% is for use in treating signs and symptoms of DED. Vevye, previously known as CyclASol, is the first and only cyclosporine solution that demonstrates efficacy in alleviating symptoms of DED after only a 4-week treatment period.⁴ Vevye targets the extensively documented inflammatory root cause of DED, consistently showcasing early and clinically significant efficacy in addressing both signs and symptoms.⁴

In 2022, the iVizia line of OTC eye care products (Théa Pharma) became available in the United States. iVizia is a preservative-free drop with an innovative, optimized bottle and unique filter cartridge designed for better patient ergonomics, reduced risk of contamination, and better calibration of drug amount delivery.⁵ The iVizia line also includes a preservative-free lubricant eye gel, which is available in a single-use vial.⁵ Povidone, trehalose, and hyaluronic acid are the active ingredients that increase tear thickness, thereby reducing ocular surface inflammation and relieving dry eye symptoms of blurred vision, burning, and itching.⁴

There has been a recent surge in popularity of the ophthalmic drug Cequa 0.09%, which is a nanomicellar topical formulation of cyclosporine.⁶ Restasis 0.05% and Ikervis 0.1% (the current forms of cyclosporine eye drops) have the disadvantages of delayed onset and the need for regular dosing.^6,7 The nanomicelles in Cequa are amphiphilic surfactants that contain hydrophobic cyclosporine A and help Cequa penetrate the tear film and the ocular structures.⁸

Xdemvy (lotilaner ophthalmic solution) 0.25% is an effective treatment for Demodex blepharitis. It is the first and only FDA-approved treatment targeting Demodex mites and is manufactured by Tarsus Pharmaceuticals.⁹ Many optometric practices see patients where Demodex blepharitis is increasingly more common.¹⁰

The pharmacologic treatment of presbyopia

The treatment of presbyopia via spectacles, contact lenses, and premium IOLs has been an integral part of optometry and ophthalmology practice for decades. The recent resurgence of pilocarpine and other pupil-constricting medication offers some hope for presbyopic patients. Certainly, pupil size, adverse effects, proper dosing, and cost are challenges for optometrists as we consider prescribing these medications. Treatment options available include the following:

Vuity (1.25% pilocarpine HCl ophthalmic solution) by Allergan is a twice-daily ophthalmic medication for presbyopia.¹¹ The second dose—an extra drop in each eye—is recommended to be applied 3 to 6 hours after the initial dose. Twice-daily dosing of Vuity by an eye care professional has the potential to extend its effectiveness for several hours.¹¹

Qlosi (0.4% pilocarpine hydrochloride ophthalmic solution) by Orasis Pharmaceuticals is an ophthalmic drug used for the treatment of presbyopia is anticipated to be available in the United States this year.^12,13 It is hoped that the lower concentration of pilocarpine will have fewer adverse effects.¹⁴ It can be used either once or twice daily.¹²

LNZ100 is an aceclidine-based eye drop by Lenz that has shown both rapid onset and long duration in phase 3 presbyopia trials. Aceclidine is a pupil-selective miotic that decouples iris stimulation from ciliary muscle stimulation.¹⁵

In-office dilation and the reversal of mydriasis

Other significant new ophthalmic drugs with the potential to impact optometric practices in the future include the following:

Eyenovia’s MydCombi is a microdose ophthalmic spray containing tropicamide 1% and phenylephrine HCl 2.5%.¹⁶ MydCombi is the first fixed-dose combination of tropicamide approved in the United States.¹⁶ It received regulatory approval in May 2023 and uses Eyenovia’s innovative Optejet device. Using a combination ophthalmic spray can improve comfort for our patients, especially children, while improving the effectiveness of mydriatics.¹⁶

Ryzumvi is an antimicrobial, preservative-free, topical eye drop formulation featuring phentolamine ophthalmic solution 0.75%.¹⁷ Its primary indication is treating pharmacologically induced mydriasis triggered by adrenergic agonistssuch as phenylephrine or parasympatholytic agents, including tropicamide. Ryzumvi is characterized as a relatively nonselective α-1 and α-2 adrenergic agonist.¹⁷ The reversal of dilation and its adverse effects has the potential to improve the safety and comfort of our patients while driving.¹⁷

Retinal disease and new ophthalmic injectables

Recent advances in ophthalmic injectable drugs for the treatment of retinal conditions such as GA include the following:

Iveric Bio received FDA approval for ophthalmic injectable Izervay (avacincaptad pegol intravitreal solution) in August 2023 for the treatment of GA caused by age-related macular degeneration (AMD).¹⁸ Izervay, a novel complement C5 inhibitor, is the only FDA-approved treatment for GA. Izervay demonstrated a significant reduction (P < .01) in the rate of progression of GA at the 12-month primary end point in 2 phase 3 clinical trials.¹⁹

Eylea HD (aflibercept 8 mg) by Regeneron was FDA approved in August 2023 for patients with wet AMD, diabetic retinopathy (DR), and diabetic macular edema (DME).²⁰ It substantially prolongs dosing intervals for patients who can now benefit from less frequent injections after their initial monthly doses and still experience the similar vision improvement, anatomic improvements, and the safety profile of Eylea.²⁰

Genentech’s Vabysmo (faricimab-svoa) was given FDA approval in October 2023 for the treatment of macular edema caused by retinal vein occlusion by intravitreal injection.²¹ Vabysmo has existing approvals for wet AMD and DME. Vabysmo inhibits 2 signaling pathways associated with these retinal conditions by neutralizing angiopoietin-2 and VEGF-A.²¹

Conclusions

Improved drug delivery systems are something that both optometrists and ophthalmologists need to understand when treating common diagnoses, such as DED, blepharitis, and presbyopia. Conventional drug delivery systems often require more frequent application or increased drug levels in their formulation, leading to improper use and patient adherence issues. Our traditional method of in-office dilation is highly effective, but can it be improved, in turn allowing patients to return to work, drive, and other activities simplifying patient education processes? Overall, innovative technologies in ophthalmic drug delivery systems are improving outcomes for our patients and their experience in our offices.

This article is an overview of the most recent ophthalmic drug delivery systems at the time of publication and is not a comprehensive list of approved options. Keep up to date on new drug delivery systems as they are approved by following Optometry Times’ website.

References:

1. König H. The history of ophthalmology, vol 1: antiquity. JAMA. 1984;251(1):93. doi:10.1001/jama.1984.03340250069032

2. Newsome DA, Wong VG, Cameron TP, Anderson RR. “Steroid-induced” mydriasis and ptosis. Invest Ophthalmol. 1971;10(6):424-429.

3. Bausch + Lomb and Novaliq announce FDA approval of Miebo (perfluorohexyloctane ophthalmic solution) for the treatment of the signs and symptoms of dry eye disease. News release. Bausch + Lomb. May 18, 2023. Accessed July 24, 2024. https://ir.bausch.com/press-releases/bausch-lomb-and-novaliq-announce-fda-approval-miebotm-perfluorohexyloctane

4. Harrow announces availability of Vevye (cyclosporine ophthalmic solution) 0.1%, the first and only cyclosporine-based product indicated for treating both signs and symptoms of dry eye disease. News release. Harrow. January 11, 2024. Accessed July 24, 2024. https://www.biospace.com/article/releases/harrow-announces-availability-of-vevye-cyclosporine-ophthalmic-solution-0-1-percent-the-first-and-only-cyclosporine-based-product-indicated-for-treating-both-signs-and-symptoms-of-dry-eye-disease/

5. Appold K. iVizia lubricant eyedrops combine hydrating and protecting ingredients to provide symptom relief. Ophthalmology Management. May 2022. https://ophthalmologymanagement.com/issues/2022/may/rx-perspective/

6. Hutton D. Cyclosporine ophthalmic solution 0.09% phase 4 data indicates sustained improvement in dry eye signs, symptoms in patients switched from cyclosporine ophthalmic emulsion 0.05%. Ophthalmology Times. October 13, 2023. Accessed July 30, 2024. https://www.ophthalmologytimes.com/view/cyclosporine-ophthalmic-solution-0-09-phase-4-data-indicates-sustained-improvement-in-dry-eye-signs-symptoms-in-patients-switched-from-cyclosporine-ophthalmic-emulsion-0-05-

7. Johnston J. How optometrists are using Cequa (cyclosporine ophthalmic solution) 0.09% to treat chronic dry eye disease. Eyes on Eyecare. April 3, 2024. Accessed July 24, 2024. https://eyesoneyecare.com/resources/optometrists-treat-dry-eye-cequa/

8. Periman LM, Mah FS, Karpecki PM. A review of the mechanism of action of cyclosporine A: the role of cyclosporine A in dry eye disease and recent formulation developments. Clin Ophthalmol. 2020;14:4187-4200. doi:10.2147/OPTH.S279051

9. FDA approves Xdemvy (lotilaner ophthalmic solution) 0.25% for the treatment of Demodex blepharitis. Tarsus Pharmaceuticals. News release. July 25, 2023. Accessed July 24, 2024. https://ir.tarsusrx.com/news-releases/news-release-details/fda-approves-xdemvytm-lotilaner-ophthalmic-solution-025

10. Trattler W, Karpecki P, Rapoport Y, Sadri E, Schachter S, Whitley WO, Yeu E. The prevalence of Demodex blepharitis in US eye care clinic patients as determined by collarettes: a pathognomonic sign. Clin Ophthalmol. 2022;16:1153-1164. doi:10.2147/OPTH.S354692

11. Hutton D. FDA approved twice-daily dosing option for Vuity eye drops for presbyopia. Optometry Times. March 31, 2023. Accessed July 24, 2024. https://www.optometrytimes.com/view/fda-approved-twice-daily-dosing-option-for-vuity-eye-drops-for-presbyopia

12. Orasis Pharmaceuticals announces FDA approval of Qlosi (pilocarpine hydrochloride ophthalmic solution) 0.4% for the treatment of presbyopia. News release. Orasis Pharmaceuticals. October 18, 2023. Accessed July 24, 2024. https://www.orasis-pharma.com/orasis-pharmaceuticals-announces-fda-approval-of-qlosi-pilocarpine-hydrochloride-ophthalmic-solution-0-4-for-the-treatment-of-presbyopia/

13. Coming soon in 2024. Qlosi. Accessed July 29, 2024. https://qlosi.com/

14. Yoo YJ, Hwang JM, Yan HK. Dilute pilocarpine test for diagnosis of Adie’s tonic pupil. Sci Rep. 2021;11(1):10089. doi:10.1038/s41598-021-89148-w

15. Lenz Therapeutics announces positive topline data from phase 3 CLARITY presbyopia trials. Lenz Therapeutics. News release. April 3, 2024. Accessed July 24, 2024. https://ir.lenz-tx.com/news-events/press-releases/detail/11/lenz-therapeutics-announces-positive-topline-data-from-phase-3-clarity-presbyopia-trials

16. MydCombi: an easy way to dilate. MydCombi. Accessed July 24, 2024. https://mydcombi.com

17. Ocuphire Pharma and Viatris announce FDA approval of Ryzumvi (phentolamine ophthalmic solution) 0.75% eye drops for the treatment of pharmacologically-induced mydriasis produced by adrenergic agonists (e.g., phenylephrine) or parasympatholytic (e.g., tropicamide) agents. Ocuphire Pharma. News release. September 27, 2023. Accessed July 24, 2024. https://www.ocuphire.com/news-media/press-releases/detail/415/ocuphire-pharma-and-viatris-announce-fda-approval-of

18. Iveric Bio announces FDA accepts new drug application and grants priority review for avacinacaptad pegol for treatment of geographic atrophy. Iveric Bio. News release. February 16, 2023. Accessed July 24, 2024. https://investors.ivericbio.com/news-releases/news-release-details/iveric-bio-announces-fda-accepts-new-drug-application-and-grants

19. Hutton D. Iveric Bio releases 24-month topline results from phase 3 study of avacincaptad pegol intravitreal solution (Izervay) for geographic atrophy. September 19, 2023. Accessed July 24, 2024. https://www.optometrytimes.com/view/iveric-bio-releases-24-month-topline-results-from-phase-3-study-of-avacincaptad-pegol-intravitreal-solution-izervay-for-geographic-atrophy

20. Eylea HD (aflibercept) injection 8 mg approved by FDA for treatment of wet age-related macular degeneration (wAMD), diabetic macular edema (DME) and diabetic retinopathy (DR). Regeneron Pharmaceuticals. News release. August 18, 2023. Accessed July 24, 2024. https://www.globenewswire.com/news-release/2023/08/18/2728276/0/en/EYLEA-HD-aflibercept-Injection-8-mg-Approved-by-FDA-for-Treatment-of-Wet-Age-related-Macular-Degeneration-wAMD-Diabetic-Macular-Edema-DME-and-Diabetic-Retinopathy-DR.html

21. FDA approves Genentech’s Vabysmo for the treatment of retinal vein occlusion (RVO). News release. Genentech. October 26, 2023. Accessed July 24, 2024. https://www.gene.com/media/press-releases/15009/2023-10-26/fda-approves-genentechs-vabysmo-for-the-