May 5, 2023 Open Letter to the Ophthalmic and Optometric Press

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OPEN LETTER TO THE OPHTHALMIC AND OPTOMETRIC PRESS

Illegal Marketing of Unapproved Amniotic Fluid Eye Drops

Dry Eye Drugs in a Post-Truth Medical Era

Dear Editors-in-Chief and Editorial Boards:

The Dry Eye Foundation is a 501(c)(3) nonprofit organization serving the ocular surface disease and ocular surface pain patient communities. Our activities include public education about eye drop safety, in particular unapproved biologic eye drops. (1) (2)

On April 10, 2023 the FDA posted a Public Safety Notification on amniotic fluid eye drops. (3) This notification read, in part:

“There are currently no FDA-approved amniotic fluid eye drops to treat, mitigate or cure eye diseases or conditions…. In addition, as these products are not FDA-approved, the agency does not have information about their manufacture, and there are no assurances that the products are safe and effective for any disease or condition.”

Two amniotic fluid eye drops have been extensively marketed through eye care trade publications: Regener-Eyes Pro and Regener-Eyes Lite. Both are manufactured by Regenerative Processing Plant LLC and distributed by Regener-Eyes LLC.

Eye care journals such as those you publish contain materials which state the following unapproved indications for these products:

Blepharitis
Corneal wounds
Corneal abrasions
Dry eye disease (mild, moderate, severe)
Exposure keratitis
Filamentary keratitis
Keratitis
Limbal Stem Cell Deficiency

Meibomian gland disease
Neurotrophic pain (sic)
Ocular surface issues resulting from surgery
Punctate epithelial keratitis
Recurrent corneal erosions
Sjögrens syndrome
Stevens-Johnson syndrome
Post EBK re-epithelialization

Regener-Eyes LLC repeatedly uses full page advertisements to promote their products. Since 2021, at least 42 full page ads for Regener-Eyes have appeared in at least seven different trade publications. (Attachment A) Two such advertisements were published the same month that the FDA Public Safety Notification was posted.

Regener-Eyes LLC also uses the influence of Key Opinion Leaders to market their products.

At least 34 Key Opinion Leaders (ophthalmologists and optometrists) authored or were interviewed for articles which mention, discuss or feature Regener-Eyes eye drops. (Attachment B)
At least 36 such articles have appeared in 12 different journals, of which 26 have been published in the past 24 months. (Attachment B)
The KOLs include ophthalmologists and optometrists who serve on Regener-Eyes LLC’s Clinical Advisory Board. (Attachment C) In a majority of articles there is no clear disclosure of this potential source of bias.
A White Paper published as a trade journal supplement, and co-authored by a (then) Clinical Advisory Board member and the owner of Regenerative Processing Plant LLC, (Attachment D) was, until recently, a central feature of the company’s advertising campaign.

Regener-Eyes LLC has never undergone a single clinical trial and cannot advertise in peer-reviewed clinical journals. Instead, its direct-to-provider marketing efforts found a natural home in the eye care industry trade magazines. Your publications unwittingly provided a veneer of legitimacy and credibility to amniotic fluid eye drops, since full-page advertisements and favorable articles by Key Opinion Leaders are typical marketing channels for FDA approved prescription drugs, and FDA compliant OTC drugs.

Damage to patient-physician relationship

Even prior to the FDA Notification, the Dry Eye Foundation received patient phone calls and emails regarding amniotic fluid eye drops. This was often prompted by the eye drops’ high cost and the aggressive telephone marketing tactics of Regener-Eyes LLC, as well as the self-evidently amateurish appearance of the bottle and label. A frequent refrain was that the drops had been recommended by their optometrists or ophthalmologists. Upon learning of the unproven and unapproved status of these products, many patients expressed dismay and distrust of their eye doctor’s quality of care and knowledge, as well as concerns about financial conflict of interest.

Your eye care industry publications have therefore, regrettably, harmed the patient-physician relationship by repeatedly promoting Regener-Eyes eye drops to ophthalmologists and optometrists.

The Dry Eye Foundation urges the Editorial Boards and the publishers of the eye care press to develop policies which prevent the marketing of unapproved or non-compliant drugs in their journals. This would include both paid advertising, and the publication of educational articles that favorably mention these products, either by name or by drug class.

Sincerely,

Sandra Brown MD, Board Member and Medical Advisor
Rebecca Petris, Executive Director
Aidan Moore, Deputy Executive Director

Notes

(1) Eyedropsafety.org

(2) Biologiceyedrops.org

(3) FDA 4/10/23 Public Safety Notification on Amniotic Fluid Eyedrops

Attachments

A: Regener-Eyes advertisements in trade journals

Full-page advertisements for Regener-Eyes appear in the following publications. (Note: Digital versions are not available earlier than 2021 for several of these publications.)

Contact Lens Spectrum: May and July 2021

Ophthalmology Management: April, October, November and December 2021; January, February, April, May, June, August, September and October 2022; April 2023

Ophthalmology Times: February and September 2021

Optometric Management: July, August and September 2021; February, March, April, May, July, August, September and October 2022

Review of Ophthalmology: September, November and December 2021; April, June, September and October 2022

Review of Optometry: March, September and December 2021; February, April, June and September 2022

Vision Monday: April 2021

Examples of ads

B: Trade journal articles mentioning, discussing or featuring Regener-Eyes

Kristine Brennan; interviewee: Darren Gregory MD (11/2016) Thicker than Water: Autologous Serum. Review of Ophthalmology

Whitney Hauser, OD (9/2018) Clinical: Dry Eye / Mail-Order Options, Optometric Management

Elizabeth Yeu, MD (12/2018) Amniotic Derived Therapies Prove Effective in Treating Ocular Surface Disease, Ophthalmology Management

Alison Bozung OD & Paul Hammong OD (8/2019) When Corneal Wounds Won’t Heal, Review of Optometry

Peter Hersh, MD, James Loden MD, Luke Rebenitsch MD (4/2020) Therapeutic Refractive Corneal Surgery, Eyeworld

Michelle Dalton; interviewee: Elizabeth Yeu MD (4/2020) Dry Eye Disease Treatment Options, Ophthalmology Management

Jill Gallagher; ref. Randall Thomas OD and Ron Melton OD (10/2020) The State of Eye Care Today, Review of Optometry

Arthur Epstein OD (1/2021) Off the Cuff: Some Secret Sauce, Review of Optometry

Joe Darrah; interviewee: Cynthia Matossian MD (3/2021) Rx Perspective: A Natural Treatment for Dry Eye, Ophthalmology Management

Steven Sorkin OD (4/2021) Corneal Dystrophies 101, Modern Optometry

n/a (4/2021) Industry Insider: Regener-Eyes Bob Colucci, Ophthalmology Management

Paul Karpecki OD (4/2021) New Options, Front to Back, Review of Optometry

Ahmad Fahmy OD (5/2021) A New Tool in the Dry Eye Armamentarium, Optometric Management

Paul Karpecki OD (5/2021) How Getting Dry Eye Right Changes Patient Lives & Easily Adds $100,000+ Annually, Review of Optometric Business

Darrell White MD (5/2021) Treating Dry Eye 401: A Master Class in Treating Complex Cases, Ocular Surgery News (5/2021)

O.D. Notebook: Maintain Patient Communication, Optometric Management

Arthur Epstein OD (6/2021) The Essentials: A Master Class in Dry Eye, Contact Lens Spectrum

Kambiz Silani OD (7/2021) Focus: Drop-in Moisture, Optometric Management

Leanne Spiegle (9/2021) Approaches and Methods for Treating Dry Eye: 2021, Review of Ophthalmology

Steven Sobel OD (11/2021) Ophthalmic Biologics, Modern Optometry

Paul Karpecki OD (11/2021) Owning OSD: New Treatments can Help Us Keep Up With This Perennial Problem, Review of Optometry

Alice Epitropoulos MD (1/2022) Treating DED in Contact Lens Patients, Ophthalmology Management

Mark Tosh; interviewee Kimberly Riordan OD (2/2022) Increasing Incidence of Dry Eye Disease Presents Opportunity for ODs, Vision Monday

Frederick Ditmars BS, Kimberly Brondeel BS, W. Samuel Fagg MSC PhD, Pamela Theriot OD (3/2022) A Double-Header: Dry Eye and Filamentary Keratitis, Modern Optometry

Rachel Dandar MD, John Sheppard MD (5/2022) Four Novel Approaches to DED Treatment, Ophthalmology Management

Jerry Robben OD, Patti Barkey COE (5/2022) How We Built Dry Eye Services That Spurred 20%+ Growth in Annual Revenue, Review of Optometric Business

C. Randall Harrell MD (5/2022) Bringing Biologics to Eye Health, Ophthalmology Times

Maria Sampalis OD (5/2022) The Technology Powering My New Dry Eye Center, Review of Optometric Business

Mahnia Madan OD, Mark Eltis OD (6/2022) From Basics to Biologics: Selecting Drops for Every Dry Eye Patient, Review of Cornea & Contact Lens

Elise Kramer OD (6/2022) Therapy Options Based on DED Severity, Optometry Times

Christopher Kuc OD (7/2022) Five Rules of Thumb for Managing the Ocular Surface, Modern Optometry

Emilie Seitz OD (7/2022) Sjögren Syndrome: Ocular Manifestations of an Underlying Systemic Disease, Modern Optometry

Arthur Epstein OD (8/2022) A Master Class in Dry Eye - Breakthroughs in Understanding and Managing Dry Eye, Contact Lens Spectrum

Mitchell Jackson MD (8/2022) Spotlight on Dry Eye: Create a Process, Offer Packages, Ophthalmology Times

Carly Rose OD (11/2022) DED: Developing a 360 Diagnosis and Treatment Plan, Optometry Times

Pam Theriot OD, Lisa Hornick OD (3/2023) Dry Eye Drugs: What’s New and What’s Next, Review of Optometry'

Catlin Nalley; interviewee James Thimons OD (3/2023) Restrictive Drug Formularies: How to Beat the Odds, Review of Optometry

Ethan Lindgren BS, Neel Pasricha MD (4/2023) Medical Management of Dry Eye Disease, Ophthalmology Management

C: Regener-Eyes Clinical Advisory Board

Source: regenereyes.com/clinical-advisory-board/ as of May 5, 2023

D: EyeWorld White Paper on Regener-eyes

Marguerite McDonald MD, Carl Randall Harrell MD (7/2021) Therapeutic Potential of Regener-Eyes Ophthalmic Solution in the Treatment of Dry Eye Disease, Eyeworld Supplement

Excerpt: “Regener-Eyes is an engineered biological product derived from human placental-based biomaterials, manufactured under current Good Manufacturing Practices (cGMP), regulated and reviewed by the Food and Drug Administration (FDA). Regener-Eyes incorporates Regenerative Processing Plant’s (RPP) proprietary patented sterilization process to provide for a safe, sterile product for clinical use.”

Conclusion: “Regener-Eyes® drops are a topical therapy for DED; they are an engineered biological product. The drops contain a large number of anti-inflammatory and trophic factors that attenuate the detrimental immune response in the eye and protect the epithelial cells of the ocular surface from injury and inflammation.1,9,12–13,15 Topical administration of Regener-Eyes® may suppress ongoing ocular inflammation, may improve meibomian gland function, and may enhance the restoration of the ocular surface barrier in DED patients, without causing treatment-related adverse events.1,13 Due to its potent immunosuppressive and regenerative properties, Regener-Eyes® should be considered as a powerful new therapeutic option in the management of DED.”