This article was originally published in a sponsored newsletter.

Ocular surface homeostasis is impacted by so many contrasting elements including the environment, topical medications and systemic and ocular disease; not to mention patients’ lifestyle choices such as screen time, lack of sleep and use of contact lenses and cosmetics, In some cases, the amount and duration of ocular surface insults do not seem to matter, but in other instances, ocular surface homeostasis is fragile and breaks quickly. Why? How does the ocular surface maintain “normal” tear film structure and cellular homeostasis under all these influences?

I have a colleague who experienced meibomian gland dropout in superior and inferior lids in both eyes, along with a slightly reduced tear film break-up time and no staining, all without dry eye symptoms. Remarkably, in one of her superior lids, she has only little nubs of meibomian glands and one large, central meibomian gland. Her case begs the question: How many glands are needed in this redundant system of checks and balances?

The ocular surface system is robust until it isn’t.

In my opinion, this is the challenge of ocular surface disease. We can’t easily predict what will have a critical impact or be “the final straw” on patients’ ocular surface homeostasis. In this issue, our columnists discuss the impact of cosmetics and lash serums—one of the many impacts on ocular surface homeostasis—as well as advice that can be provided to patients. Currently, we try to make connections in retrospect after a patient is diagnosed with ocular surface disease, rather than predicting ocular surface disease before it happens. Ultimately though, artificial intelligence may help clinicians put together all the pieces to the puzzle that seem unrelated. Wouldn’t it be nice to advise patients that the risk of dry eye could be reduced with changes that are specific to them?

I look forward to the day of simplifying, rather than complicating, ocular surface disease. It will be here before we know it.

Kelly K. Nichols, OD, MPH, PhD
Editor

Out of Sight, Out of Mind

How often do patients arrive at your office and say, “I didn’t wear my eye makeup because I knew you’d mess it up!”? This sentiment brings up an important aspect of eye care that often goes unchecked: What makeup, lash serums and other at-home products are your patients using to enhance their eye appearance? Unfortunately, patients don’t always link what’s best for their comprehensive eye care to what they want from their beauty care, and they likely don’t know what they don’t know when it comes to the delicate area in and around their eyes. This concern applies to many products and ingredients, but this month, we’re talking about prostaglandins.

Some lash serums and many popular eye makeup brands contain prostaglandins and synthetic prostaglandin analogs—such as isopropyl cloprostenate—that can promote inflammation and lead to ocular surface damage. For example, when used in glaucoma medications (which was the original use for which prostaglandin analogs were designed), patients experienced a significant growth in lashes, but they also showed signs of conjunctival hyperemia and meibomian gland dysfunction.¹

When asked, our patients report a variety of symptoms, from ocular redness, burning, itching or blurred vision to foreign body sensation as result beauty enhancements. false lashes lash extensions are easy recognize causative factors, but we may not have clear idea other products that using if don’t ask. they certainly won’t volunteer information, especially it mean discontinuing self-care regimen enjoy. therefore, it’s important for us foster open communication and understanding with so feel comfortable answering questions.

Doing research and finding a couple of good brands that don’t have prostaglandins will put patients at ease because you can offer an effective compromise: Patients can continue their self-care routine with products that we know won’t damage their ocular surface. For the last few years, I’ve recommended Twenty/Twenty Beauty and Eyes Are The Story as brands that don’t use prostaglandins, and recently, Bausch + Lomb launched a new prostaglandin-free OTC lash and brow serum that I intend to share with my patients.

Taking a different approach to understanding our patients’ lifestyles is key to setting a good foundation for treatment. All the work we do evaluating, prescribing, advocating and treating can be undone unknowingly by patients every time they use their seemingly innocuous beauty products. However, simply asking about their skin care and beauty regimens can clear possible roadblocks to successful outcomes.

References:

1. Sullivan DA, da Costa AX, Del Duca E, et al. TFOS lifestyle: impact of cosmetics on the ocular surface. Ocul Surf. 2023 Jul;29:77-130. doi:10.1016/j.jtos.2023.04.005

At its core, dry eye disease (DED) is an imbalance of ocular surface homeostasis. Alterations in osmolarity and pH result in damage to the epithelial cells, triggering a cascade of inflammatory mediators that includes prostaglandin E2 (PGE2) and interleukin-17 (IL-17). This response is a key factor in the continuous development of DED and a wide range of biological actions caused by PGE2:

• Increased vascular permeability during the inflammation process
• Pain and hypersensitivity
• Effects to the thermoregulatory center
• Local tissue edema

The production of these inflammatory mediators in turn prompts the immune system to produce T helper cells. These immune cells have been linked to a variety of autoimmune conditions, including inflammatory bowel disease, uveitis/scleritis and rheumatoid arthritis. A newly discovered type of T helper cell, known as Th17, is thought to have a prominent role in the inflammatory cycle and has been linked to the development and continuation of DED specifically.

This study aimed to explore whether PGE2 can promote the progression of Th17-induced DED using a dry eye mouse model.¹ Two groups of mice were used in the study. Group 1 compared control mice to mice that were induced into a dry eye (DE) model via subcutaneous scopolamine injection in order to assess production of PGE2 and other signs of DE. Group 2 was designed to determine whether PGE2 could induce DE symptoms. These mice were divided into control, PGE2 and PGE2 plus AH6809 cohorts. PGE2 was administered via an ocular surface drip. AH6809 was used to inhibit the PGE2 receptor to determine whether the results seen via the PGE2 drip were specific to the application of PGE2.

Results from Group 1 demonstrated that the DE model was successfully established. PGE2 levels were significantly higher in the experimental group as compared to controls. Additionally, the tear break-up time (TBUT) and tear secretion was lower in the experimental group as compared to controls. Taken together, these outcomes indicate that PGE2 was highly expressed in the DE mouse model.

In Group 2, PGE2 effectively suppressed tear production and repressed TBUT. AH6809 significantly reversed PGE2 inhibition upon tear production and TBUT repression, indicating that PGE2 could induce DE-like symptoms; PGE2 receptor blockage alleviated the effects of PGE2 on DE.

Additionally, the authors concluded that PGE2 increases IL-17 concentration in tears and increases Th17 cell proportion in DE. PGE2 inhibition by AH6809 also reversed the effects of PGE2 on Th17 cell proportion. The study findings indicate that PGE2 may be a new target for the treatment of DE.

References:

1. Chen J, Gong Y, Sun X, et al. Prostaglandin E2 may clinically alleviate dry eye disease by inducing Th17 cell differentiation. Chem Biol Drug Des. 2024 Feb;103(2):e14477. doi:10.1111/cbdd.14477

Prostaglandin E2 may clinically alleviate dry eye disease by inducing Th17 cell differentiation

Jingyao Chen, Yu Gong, Xiaoyu Sun, Nuo Chen, Zijun Zhao, Weijia Zhang, and Yixin Zheng
Chem Biol Drug Des. 2024 Feb;103(2):e14477. doi:10.1111/cbdd.14477

Dry eye (DE) is a multifactorial ocular surface disease characterised by an imbalance in tear homeostasis. The pathogenesis of DE is complex and related to environmental, immunological (e.g., T helper 17 cells) and other factors. However, the DE disease pathogenesis remains unclear, thereby affecting its clinical treatment. This study aimed to explore the mechanism through which prostaglandin E2 (PGE2) affects DE inflammation by regulating Th17. The DE mouse model was established through subcutaneous injection of scopolamine hydrobromide. The tear secretion test and break-up time (BUT) method were used to detect tear secretion and tear film BUT, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of PGE2, interleukin (IL)-17, IL-6 and tumour necrosis factor (TNF-α) in tear fluid and those of PGE2 and IL-17 in the serum. RT-qPCR and western blotting were used to test the mRNA and protein expression levels of IL-17 and retinoid-related orphan receptor-γt (RORγt). PGE2 was highly expressed in the DE mouse model. The mRNA and protein levels of IL-17 and the key Th17 transcription factor RORγt were increased in tissues of the DE mice. Moreover, PGE2 promoted tear secretion, reduced the BUT, increased the IL-17 concentration in tears and increased the Th17 cell proportion in DE, whereas the PGE2 receptor inhibitor AH6809 reversed the effects of PGE2 on tear secretion, BUT, and the Th17 cell proportion in draining lymph node (DLN) cells. Taken together, the study findings indicate that PGE2 could induce DE-related symptoms by promoting Th17 differentiation.

Prostaglandins and Non-Prostaglandins in Cosmetics

The eyelash serum market is well on its way to becoming a billion-dollar industry by 2031.¹ Whether we like it or not, many of our patients will reach for these products to boost their lash length, while inadvertently exposing their eyes to ingredients that can have detrimental effects to their ocular surface in the process. Simply telling our patients not to use these products, however, is about as effective as forbidding my two-year-old from eating an ice cream cone as soon as I turn my back. So, how should we advise our patients to ensure that we’re giving scientifically-backed guidance while respecting their desire to enhance their appearance?

The main ingredients in eyelash serum are generally classified as prostaglandin analogs (PGAs) or non-PGAs. We know that bimatoprost is the only FDA-approved molecule that has been extensively studied for eyelash growth efficacy and safety, and while that knowledge brings some comfort when patients ask for product recommendations, we also know that FDA approval doesn’t confer safety. It can only provide a side effect profile that was deemed tolerable at the time of review. Further, dechloro ethylcloprostenolamide and isopropyl cloprostenate (ICP) are two common yet non-FDA-approved PGAs found in OTC lash serums, and neither has been adequately studied in terms of efficacy or safety.²

In a 2022 study by Rahman, et al., 64 eyelash serums were evaluated by liquid chromatography tandem mass spectrometry to identify their components.³ Four products contained bimatoprost, but only one declared it as an ingredient. Eight other serums contained unknown PGAs that have never been used in pharmaceuticals, suggesting that manufacturers do not always fully disclose their ingredients list.³ In short, with all of these possible ingredient issues, PGAs that have been evaluated by the FDA for long-term use—even for different indications—carry a higher recommendation than unstudied PGAs, such as dechloro ethylcloprostenolamide, ICP and other unknown molecules.²

It’s worth mentioning, however, that prostaglandin-associated periorbitopathy (long-term periocular changes and orbital fat atrophy due to PGAs) was not known at the time of bimatoprost’s FDA approval. One could argue that PGAs favor short-term beauty outcomes at the expense of a long-term youthful appearance.

There’s a long list of non-PGA ingredients in OTC lash serums that purportedly enhance lash length: peptides, growth factors, panthenol, proline, pumpkin seed oil, Jarilla-Coffea extract and castor oil.² They all have different and multifaceted mechanisms of action, but they, too, have been understudied,² and patients should still be cautioned against the use of understudied products.

Fellow eye doctors are encouraged to pump the brakes on recommending poorly studied OTC lash serums to patients. The well-known skincare company Rodan + Fields was part of three separate class-action lawsuits due to side effects associated with ICP in their product, including macular edema, iris color change and ocular irritation.⁴ For those wary of pharmaceuticals, magnetic eyelashes are yet another option. That topic, though, is worthy of an entirely different column!

References:

1. Correa D. Eyelash serum market to reach $1.3 Bn, globally, by 2031 at 5.7% CAGR: Allied Market Research. PR Newswire. June 8, 2022. Accessed July 10, 2024. https://www.prnewswire.com/news-releases/eyelash-serum-market-to-reach-1-3-bn-globally-by-2031-at-5-7-cagr-allied-market-research-301563924.html
2. Baiyasi M, St. Claire K, Hengy M, Tur K, Fahs F, Potts G. Eyelash serums: a comprehensive review. J Cosmet Dermitol. 2024 Jul;23(7):2328-2344. doi:10.1111/jocd.16278
3. Rahman MS, Yoshida N, Hanafusa M, et al. Screening and quantification of undeclared PGF2⍺ analogs in eyelash-enhancing cosmetic serums using LC-MS/MS. J Pharm Biomed Anal. 2022 Sep;219:114940. doi:10.1016/j.jpba.2022.114940
4. Lewis, et al. v. Rodan & Fields, LLC. United States District Court for the Northern District of California. Case No: 4:18-cv-02248-PJH. Accessed July 10, 2024. https://krcomplexlit.com/currentcases/rodan-fields-lash-boost-litigation