Laura M. Periman, MD

home

authors

laura-m-periman-md

Research indicates that because nocturnal evaporative stress is a frequently overlooked and undermanaged component of dry eye care.

We frequently educate our patients on the role of sleep as a facilitator of overall good health. But what happens when our diligent sleepers wake up with dry eye symptoms that are decidedly worse, not better?

The strange phenomena of my patients getting more and better sleep-and still waking up with peak severity dry eye symptoms-led me to investigate the cause of, and potential remedies for, symptomatic dry eye that worsens overnight.

According to recent research published by Korb, Blackie, and Nau in 2017, poor eyelid performance while sleeping-and subsequently, the 

 that follows-is prevalent in patients suffering from refractory dry eye. Further, they identified that poor lid performance correlates relatively neatly with moderate-to-severe symptoms.

This research is significant because NES is a frequently overlooked and undermanaged component of dry eye care. By taking a more proactive approach to identifying and managing this nuanced set of aggravators, we can help soften our patients’ symptoms and boost their quality of life.

First, we should recognize that the severity of nocturnal evaporative stress is influenced by both external and internal factors as well as 

External factors, such as those studied by Korb et. al., are essentially biomechanical failures: for instance, poor lid performance, sleeping position preference or the presence of floppy eyelid syndrome (which has been shown to negatively impact the tear film’s functionality).

Internal factors may include medications, allergic responses to dust mites, or direct contact with turbulent vent and fan air, all of which can induce desiccating stress that damages the eye’s protective layers, aqueous or lipid.

Dry eye practitioners are good at investigating external factors. Most of us already advise our dry eye patients to avoid fans and allergens and review the medications list for relevant drying side effects. More careful examination for evidence of poor nocturnal lid performance is a good place to start, as diagnostic testing and remedial options are both straightforward and effective.

Intense Pulsed Light Therapy For The Treatment Of Chalazia

However, from my experience talking to patients and colleagues, we can improve our considerations and assessments for a wider range of internal factors with improved knowledge of common ocular surface drying medications.  

To test my patients’ lid performance in clinical examination, I have adopted the Korb-Blackie lid leak test, which was described as a way to evaluate dry eye symptom prevalence and severity with respect to lid closure.

The test itself is simple: in a darkened room, place a muscle light or transilluminator gently at the upper tarsus of the closed eye, and direct the light toward the interpalpebral fissure. If light escapes between the eyelids, it is a positive test. More light leakage indicates a more significant nocturnal lid seal insufficiency which is associated with more exposure/desiccating stress and greater symptom severity.

The test is so simple and informative, I made it a part of my standard dry eye diagnostic workup. It takes 15 seconds to perform. We record this in the EMR as “Lid Seal Insufficiency”-negative, mild, moderate, or severe-based on the amount of light leaking in between the closed eyelids.

I complement this test by performing an even simpler “snap test:” pulling gently on the patient’s upper and lower lids to assess elasticity, with slow return to normal position indicating a lack of elasticity, and subsequently, lid performance.

Lift the upper lids to look for excess laxity, papillary reaction of the superior palpebral conjunctiva. These two findings, in addition to temporal upper eyelash ptosis, suggests floppy eyelid syndrome and a sleep study for obstructive sleep apnea is ordered.

If light is escaping, the lids are not adequately protecting the ocular surface. A special eye mask can make a significant difference for these cases. Clinically, I’ve observed in cases of asymmetric lid seal insufficiency that the meibomian gland drop is often more pronounced on the more severe lid seal insufficiency side.

Once I identify poor nocturnal lid protection, I instruct the patient to take a series of proactive steps to protect the ocular surface from overnight desiccating stresses, even if he or she does not report disproportionate pain or discomfort in the morning. First, I instruct them to direct fans and vents well away from the head. I also tell them to avoid dust-mite allergens (dust mite pillow covers, mattress covers, and weekly hot water washings of bedding).

If the patient’s lid seal insufficiency is mild and the signs and symptoms are mild, I may suggest over-the-counter preservative free lubricating gels and ointments. However, these topicals may dry out overnight and patients may report increased morning irritation and discomfort. I am increasingly recommending my patients purchase a high-quality sleep mask.

The silicone, medical-grade products offered by Eye Eco, particularly Eye Seals, work very well in my patients. Patients readily adapt to the masks and some even report improved sleep (by keeping out ambient light and early morning light). Typically, patients also report improved morning eye comfort and satisfaction with the masks, provided they are properly cleaned and maintained.

This simple approach to identifying and managing poor nocturnal lid protection is, in my opinion, particularly helpful for patients with micro-exposures, since reduction of ongoing desiccating stress may help us manage MGD.

Research from James Jester, et. al. showed that inducing desiccating stress in mice created an altered protein-to-lipid ratio in the meibomian gland, inducing MGD in this in vivo mouse model.

 Specifically, the meibomian glands upregulated cell turnover in response to desiccating stress, inducing faster meibum production yet with an abnormal protein-to-lipid ratio.

As with any animal study, it is important to realize the limitations of early research and base clinical decisions primarily on human-based evidence. However, we understand that MGD is a complex, multifactorial condition that heavily influences the broader dry eye “vicious circles,” so to speak.

By aggressively treating nocturnal evaporative stress in our MGD patients, we have potentially much to gain with very little or nothing to lose. Controlled moist heat masks may help promote healthy meibomian gland function, as well as improve signs and symptoms of MGD as part of homecare continuance of in-office therapeutic processes like LipiFlow.

As busy practitioners, we are often forced to minimize our patient consultation time and see as many patients as possible. Accordingly, it is tempting to run new dry eye patients through a minimalist protocol or script that covers the basics: medication, lifestyle, and other surface-level factors that provide important, but not comprehensive information.

Taking a few extra seconds to examine a little deeper and identify nocturnal evaporative stress is worth the time spent. Simply asking your dry eye patients “How do your eyes feel upon awakening?” and using the lid seal test provides us a very efficient way to simply make a big difference for our dry eye and MGD patients. If we, as practitioners, are going to recommend patients focus on good sleep hygiene and habits, we should also ensure that their eyes are also getting full rest from drying exposures.

Sharpen Your Medical Mind. Be A Dry Eye Sleuth.

Dr. Periman reports she is a speaker for Allergan, Lumenis, Shire, Takeda, Novartis, and Sun Pharmaceuticals. Dr. Periman serves as a consultant for Eyedetec, Eyevance, Science Based Health, TearLab, Visant, and Umay.

1. Korb, D. Blackie, C. Nau, A. Prevalence of Compromised Lid Seal in Symptomatic Refractory Dry Eye Patients and Asymptomatic Patients. 

Investigative Ophthalmology & Visual Science.

2. Liu, D. et. al. Tear Film Dynamics in Floppy Eyelid Syndrome. 

3. Korb, D. Blackie, C. The Korb-Blackie Lid Light Test. 

Investigative Ophthalmology & Visual Science

4. Sulahim, J. et. al. Effect of Desiccating Stress on Mouse Meibomian Gland Function. 

Articles

Poor eyelid performance while sleeping a common contributing factor

Physicians should investigate nocturnal evaporative stress in dry eye patients

Any time we perform ocular surgery—whether 

, oculoplastic, or any other ocular procedure—we want to set the patient up for success. 

Part of that is addressing any potential sources of infection, inflammation, and ocular surface disease that could complicate the postoperative course. It is common to see patients with meibomian gland dysfunction (MGD), dry eye disease (DED), and blepharitis.

For long-term efficacy, therapeutic choices are focused on the underlying cause or causes of the problem. 



Considering Demodex infestation and cataract surgery

 was 1 potential cause that we tended to overlook or ignore, because there was little we could do to address the specific problem of 

 mite infestation. 

Now we are beginning to understand the role of 

 in blepharitis and inflammatory DED, and the treatment outlook has markedly improved.


 is the presence of collarettes, or cylindrical dandruff, at the base of the eyelashes.

 

These waxy collarettes are the waste material of 

 mites living inside the hair follicles. When you regularly look for collarettes, you’ll likely be surprised at how common 

About 84% of people 60 years or older have 

 infestation, as do 100% of patients 70 years or older.

 overpopulation as well, particularly those with MGD and keratitis.

 

The higher incidence in older populations is not well understood. We hypothesize that the natural defenses and skin barrier function may be compromised with age, allowing 

 to gain the upper hand, but we do not know for certain.



Drop shows effectiveness for Demodex blepharitis in phase 2a stud

 can have a spectrum of manifestations, from asymptomatic infestation to significant blepharitis inflammation. 

Generally, significant 

 infestation results in significant inflammation. Patients have classic dry eye and blepharitis symptoms, including dry or gritty feeling, foreign body sensation and fluctuating vision. 

Because mites inside the lash follicles cause the condition, patients also can have follicular distention, hyperplasia, eyelash loss, and eyelid keratinization.

 blepharitis and bacterial blepharitis are also strongly correlated.


Despite its prevalence, there have been few treatments for 

 infestation, and there are no treatments approved for that specific indication. 

Although many patients with 

 infestation come to me having already been prescribed an immunomodulator such as cyclosporine (Cequa; Sun Pharma; Restasis; Allergan) or lifitegrast (Xiidra; Novartis), these medications treat the ocular surface sequelae of 

 infestation rather than the infestation itself. 



Making dry eye manageable for patients working from home


We could hypothesize that these medications might increase the ability to fight 

 by reducing inflammation and improving skin health, but we do not have evidence to support that idea.

Certain comorbidities, such as diabetes, place patients at higher risk for 

 blepharitis, so a primary care physician should help manage any systemic condition that has not been adequately controlled. 

To prepare a patient with 

 infestation for surgery, I usually use a combination of mechanical and chemical methods to remove collarettes, kill mites, and enhance skin barrier function in the patient.



For patients, home maintenance is important to help keep the 

 population under control. It is key to communicate this to patients.

In the office, we can perform microblepharoexfoliation using mechanical tools (AB Max; Myco Industries; BlephEx) or kits that combine tools and agents to treat Demodex (Cliradex; Bio-Tissue; ZEST; Zocular).



Where to start with treating OSD patients

and rosacea, intense pulsed light (IPL) therapy (Optima IPL; Lumenis) can be used to decrease the 

 burden in patients also afflicted with rosacea.

, ivermectin can be prescribed orally or topically (Soolantra; Galderma) to control the facial Demodex burden.


At home, good hygiene is essential to keep 

 under control after in-office treatment, but traditional shampoos are not very effective. 

Cleansing towelettes with 4-terpineol isolate (Cliradex; Bio-Tissue), the miticidal component of tea tree oil, have the highest antidemodectic activity of all the commercial cleansers.


Patients use the towelettes to clean the eyelids, lashes, and face. Hypochlorous acid cleanser (Avenova; NovaBay Pharmaceuticals), which I use for many dry eye patients, has minimal effect on 

but it can be used as a complementary therapy to 4-terpineol isolate.

Patients can also use a device at home that cleans the eyelid margins and stimulates the meibomian glands (NuLids; NuSight Medical), as well as gel cleaner for the eyelids and lashes (ZocuShield; Zocular).


 blepharitis are very new, and more treatments are in development. They are the consequence of our growing understanding of the disease and the pressing need to address it effectively. 

We have gone from strictly mechancal approaches to removing the mites, to chemical options, to the possibility of pharmaceutical options for the treatment of patients with this issue.



Amid pandemic, friendly bugs can help protect the eye from infection

 burden that is driving blepharitis and inflammation is growing rapidly, making it easier than ever to resolve the problem before elective surgery and keep patients on track long term. 




Periman is an ocular surface disease expert and director, dry eye services and clinical research, Periman Eye Institute, Seattle, Washington.

1. Gao YY, Di Pascuale MA, Li W, et al. High prevalence of Demodex in eyelashes with cylindrical dandruff. 

. 2005;46(9):3089-3094. doi:10.1167/iovs.05-0275

2. Liu J, Sheha H, Tseng SCG. Pathogenic role of Demodex mites in blepharitis. 

2010;10(5):505-510. doi:10.1097/ACI.0b013e32833df9f4

3. Liang L, Liu Y, Ding X, Ke H, Chen C, Tseng SCG. Significant correlation between meibomian gland dysfunction and keratitis in young patients with Demodex brevis infestation. 

. 2018;102(8):1098-1102. doi:10.1136/bjophthalmol-2017-310302

4. Fishman HA, Periman LM, Shah AA. Real-time video microscopy of In vitro Demodex death by intense pulsed light. 

2020;38(8):472-476. doi:10.1089/photob.2019.4737

5. Cheung IMY, Xue AL, Kim A, Ammundsen K, Wang MTM, Craig JP. In vitro anti–demodectic effects and terpinen-4-ol content of commercial eyelid cleansers. 

 2018;41(6):513-517. doi:10.1016/j.clae.2018.08.003

6. Kabat AG. In vitro demodicidal activity of commercial lid hygiene products. 

 2019;13:1493-1497. doi:10.2147/OPTH.S209067

New options open possibilities for treatment, resulting in better outcomes for patients.


Treating Demodex blepharitis efficiently before surgery

,” a blog series featuring contributions from members of the ophthalmic community. These blogs are an opportunity for ophthalmic bloggers to engage with readers with about a topic that is top of mind, whether it is practice management, experiences with patients, the industry, medicine in general, or healthcare reform. “

” continues with this latest piece by Laura Periman, MD. The views expressed in these blogs are those of their respective contributors and do not represent the views of 

The headlines are disturbing: Vaping has been linked to deaths, as well as lung transplants for otherwise healthy teens. 

What’s going on? What are the implications for the eyes?

We know that exposure to any smoke can inflame the ocular surface, but what about vapor from vaping? Can vaping affect other parts of the eyes as well?

Ophthalmology can 'adopt' technologies from other specialties 


	Unlike cigarettes, which contain the amount of nicotine that naturally occurs in tobacco, vaping fluid contains extracted nicotine in levels that are uncontrolled and often unknown.

Doctors are seeing nicotine-induced illness (“nic-sick”), particularly in teens.

 This includes seizures, anxiety, depression, cognitive compromise, and inattention.

Pictured: A 36-year old ocular surface disease (OSD) meibomian gland dysfunction (MGD) patient who frequently uses vaped THC.
	

Effects of nicotine on the eye include pupil constriction

 and reduced retinal activity visible on electroretinogram (ERG).

 Treating dry eye with recombinant human nerve growth factor 

Vaping fluid is packed with other chemicals.


	In addition to nicotine, vaping fluid components include acrolein (2-propenal), an aldehyde that severely limits regulatory t-cells - a mechanism that can thereby activate and contribute to chronic dry eye disease (DED).

Carriers and flavor additives can also cause lung toxicity and directly activate the transit receptor potential (TRP) of the ocular surface immune system and corneal nerves.

Some vaping chemicals may also activate the immune mechanism of chronic 

 Other potential components have additional health implications as well, including nitrosamines, benzaldehyde, benzyl alcohol, propylene glycol, and ethylene glycol.
	
	

New for 2020 and beyond: Dry eye disease agents in pipeline 


	The rash of cases where vapers experienced severe lung toxicity requiring lung transplants occurred after a change in manufacturing resulted in the addition of vitamin E to some vaping cartridges.

A retrospective analysis of the vaping fluid composition showed that 100% of the cartridges used by the affected patients contained vitamin E, which had not been present in the same cartridge brand in the past. The sticky ester was used as a filler, but it is not safe for inhalation.
	
	

Nutrition a priority for dry eye patients 

Without regulation, it is impossible to know if or when other potentially dangerous substances will be added to vaping fluid in the future. The reputation of the brand does not confer pulmonary or other organ system safety to our patients.

Researchers are now studying OSD and vaping.


	One recent paper looked at ocular surface findings in vapers versus non-vapers and found that vapers had staining and compromised tear breakup time.

Schirmer’s tests were inconsistent in the vaping group, and may be attributed to compensatory lacrimal gland output phases of dry eye disease, which can burn out over time. 
	
	

 Diving into dry eye can help physicians solve patients' woes


	After reading more about the chemicals involved in vaping and their effects, I believed more than ever that treatment for 

 includes educating patients on natural and self-induced environmental challenges.

Particularly, if they are exposed to chemicals that may affect the inflammatory cycle, then treatments that reduce inflammation-such as omega-3 fatty acids (HydroEye, ScienceBased Health), cyclosporine (Restasis, Allergan; Cequa, Sun), lifitegrast (Xiidra, Novartis), intense pulsed light therapy (Optima IPL, Lumenis) and thermal in-office modalities (TearCare, Sight Sciences; iLux, Alcon; and LipiFlow, Johnson & Johnson Vision)-may be offered to help tip the scales in the positive direction.
	
	

 Ocular surface inflammation: Vicious cycle of ocular surface disruption 

Most importantly, I’ve added vaping to my practice’s Dry Eye Services intake form. I want to know if patients vape, as well as if they’re routinely exposed to vaping secondhand.

My patients need to understand the risks they’re taking for their eyes and their overall health. Physician efforts to educate patients often result in improved patient health.
	
	

Dr. Periman is an ocular surface disease expert and director of Dry Eye Services and Clinical Research in Seattle, Washington.

Effect of vaping on the eyes

Patients can benefit as physicians take advantage of new treatment options 

Many medical specialties share medications and technologies, from various classes of drugs to diagnostic testing and surgical instruments.
	
	In ophthalmology, we tend to see ourselves as set apart from most specialties because of the unique needs and limitations of working with the eye. We’ve seen a few crossovers, particularly from aesthetics. Here are a few “adopted” technologies we’re happy to see in the hands of ophthalmologists.
	
	


	IPL therapy has been used in aesthetics since the 1990s to improve skin texture and treat rosacea. First-generation platforms required tremendous expertise, but newer, sixth-generation technologies (Optima IPL with the OPT technology, Lumenis), coupled with corneal shields, have the safety profile needed to address the eyelid and adnexa.
	
	


	
	Dozens of peer-reviewed papers report the efficacy of IPL as an effective drug-free approach to treating ocular rosacea-associated and non-rosacea-associated meibomian gland dysfunction (MGD) and DED. This effect is thought to occur via multi-level impacts on the inflammation factors that drive both the MGD and DED components of ocular surface disease.
	
	IPL has been shown to improve noninvasive tear breakup time more than five seconds over baseline, and 86% of patients report improved symptoms. With three or four IPL treatments, spaced two to five weeks apart, we observe reductions in MMP-9 levels and improved tear osmolarity. Patients then repeat IPL one or two times per year, depending on the severity of the underlying disease comorbidities.
	
	


	In recent years, we have seen several topical medications migrate both ways between aesthetics and ophthalmology. Few ophthalmic pharmaceuticals have transitioned into the aesthetic world like the topical drug, bimatoprost. Widely used for glaucoma, the drug’s side effect of increased eyelash growth led to its rebranding for aesthetic treatment of hypotrichiasis (Latisse, Allergan).
	
	In addition to the aerodynamic impacts on evaporative 

 from the abnormal eyelash lengthening effect associated with overuse, prostaglandins can also create lid margin redness, discoloration, dermatitis, and exacerbation of MGD. XAF5, a topical prostaglandin ointment by Topokine Therapeutics, is undergoing phase IIb/III trials to assess its efficacy in treating lower eyelid steatoblepharon.
	
	

(PODCAST) Episode 8: It's time to add IPL therapy to your toolbox


	
	Hyaluronic acid gel (HAG) fillers have been used in intraocular surgery for decades. The aesthetic uses of HAG products such as Juvederm (Allergan) and Restylane (Nestle Skin Health) are well known and offer a popular method of non-invasive facial rejuvenation.
	
	However, more recently, the functional use of fillers to improve eyelid malposition or mid-face revolumization has shown promise. HAG has been found to be as efficacious as allograft dermal grafting or hard palate grafting to improve the position of the lower eyelids, as well as to improve and restore normal eyelid anatomy.
	
	Ophthalmology, dermatology, and aesthetics benefit each other through shared medications and technologies. In the future, we anticipate seeing many more crossovers and “adopted” technologies used routinely in ophthalmology.
	
	


	Dr. Periman is an ocular surface disease expert and director of Dry Eye Services and
	Clinical Research in Seattle, WA.
	
	


	Dr. Shah is founder of SF Gotox, a Mobile Aesthetic Care Company in the Bay Area, CA.

1. Liu R, Rong B, Tu P, et al. Analysis of Cytokine Level in Tears and Clinical Correlations After Intense Pulsed Light Treating Meibomian Gland Dysfunction. 

 2017 Nov;183: 81-90.
	2. Craig JP, Chen YH, Turnbull PR. Prospective trial of intense pulsed light for the treatment of meibomian gland dysfunction. 

 2015 Feb 12;56(3):1965-70.
	3. Yin Y, Liu N, Gong L, Song N. Changes in the Meibomian Gland After Exposure to Intense Pulsed Light in Meibomian Gland Dysfunction (MGD) Patients. 

. 2018 Mar;43(3).
	4. Scott AB, Miller JM, Shieh KR. Treating Strabismus by Injecting the Agonist Muscle with Bupivacaine and the Antagonist with Botulinum Toxin.

 2009 Dec;107:104-109.
	5. Romanov A, Pokushalov E, Ponomarev D, et al. Long-term suppression of atrial fibrillation by botulinum toxin injection into epicardial fat pads in patients undergoing cardiac surgery: Three-year follow-up of a randomized study. 

 2019 Feb;16(2):172-177.
	6. Park J, Park HJ. Botulinum Toxin for the Treatment of Neuropathic Pain. 

. 2017 Sep; 24;9(9):260.
	7. Diel RJ, Kroeger ZA, Levitt RC, et al. Botulinum Toxin A for the Treatment of Photophobia and Dry Eye. Ophthalmology. 2018 Jan; 125(1): 139–140.
	8. Ho MC, Hsu WC, Hsieh YT. Botulinum Toxin Type A Injection for Lateral Canthal Rhytids. 

. 2014;132(3):332- 337.
	9. Lu R, Huang R, Li K, et al. The influence of benign essential blepharospasm on dry eye disease and ocular inflammation. 

 2014 Mar;157(3):591-7.e1-2.
	10. Gumus K, Lee S, Yen MT, Pflugfelder SC. Botulinum toxin injection for the management of refractory filamentary keratitis. 

 2012 Apr;130(4):446-50.
	11. Sahlin S, Chen E, Kaugesaar T. Effect of eyelid botulinum toxin injection on lacrimal drainage. 

. 2000 Apr;129(4):481-6.
	12. Fouda SM, Mattout HK. Comparison Between Botulinum Toxin A Injection and Lacrimal Punctal Plugs for the Control of Post-LASIK Dry Eye Manifestations: A Prospective Study. 

. 2017 Jun;6(1):167-174.
	13. Singh S, Ali MJ, Paulsen F. A review on use of botulinum toxin for intractable lacrimal drainage disorders. 

. 2018 Oct;38(5):2233-2238.
	14. MÃ©rida S, Palacios E, Navea A, Bosch-Morell F. New Immunosuppressive Therapies in Uveitis Treatment. 

 2015 Aug 11;16(8):18778-95.
	15. Goldberg RA, Lee S, Jayasundera T, et al. Treatment of lower eyelid retraction by expansion of the lower eyelid with hyaluronic Acid gel. 

. 2007 Sep-Oct;23(5):343-8.
	16. Mancini R. Managing eyelid malpositions with hyaluronic acid gel injections. 