Dry eye is a chronic disease that may begin in childhood

Blepharitis is one of the few diseases that lasts a lifetime, James M. Rynerson, MD, told Primary Care Optometry News. “We wouldn’t possibly think that for an 80-year-old with dry eye disease, the problem started when they were a baby.”

Rynerson believes the process of blepharitis and, hence, dry eye, begins in infancy, when a biofilm forms on the lids in the first few months to years of life.

As more studies help define the natural progression of dry eye in its various forms and new diagnostics help objectively measure this progression, John A. Hovanesian, MD, FACS, sees dry eye management becoming more proactive and glaucoma-like.

According to Hovanesian, the likelihood of a person developing dry eye later in life is equal to their age in percentage, which he credits learning from Richard Lindstrom, MD, Ocular Surgery News medical editor and PCON Editorial Board member. For example, a 50-year-old has a 50% chance, and an 80-year-old has an 80% chance.

“If that’s the progression, it means there’s early disease happening somewhere that we’re missing in the majority of patients that need treatment,” Hovanesian said.

“Providers should seek out patients who have the signs, but maybe not the symptoms, and treat the symptoms we do see aggressively enough to wipe them out,” he said. “Treat dry eye more like glaucoma, where you don’t rely on symptoms, but on signs to judge its progress.”

Image: Hogan CL

Casey L. Hogan, OD, FAAO, owner of Advanced Eye Care Professionals, and Richard L. Maharaj, OD, FAAO, clinical director at eyeLABS Optometry and Center for Ocular Surface Diseases, have established niches in dry eye management in Chicago and Toronto, respectively.

Often the symptoms are much greater than the clinical signs, they said.

Dry eye can confuse providers, as patients often come in with specific complaints, often referred to as “pain, no stain,” which can lead to misunderstanding, Hogan told PCON.

Maharaj said he manages dry eye proactively, simply by looking for it, daily.

“I think dry eye is in most of our chairs, most of the time,” he said in an interview. “I look for it and ask questions.”

Severe dry eye can be debilitating, Hovanesian said, and more aggressive, earlier intervention may be the answer.

Scott Schachter, OD, who practices in Pismo Beach, Calif., said he follows the guidelines from the Tear Film and Ocular Surface Society’s Dry Eye Workshop (DEWS), classifying patients in levels 1 through 4.

“All I did was listen to the expert consensus and I started finding a lot more dry eye,” he said.

Schachter said that when he lectures he often is introduced as an optometrist who treats dry eye “aggressively.”

“I’m not aggressive,” he said. “I’m simply appropriately treating.”

Dry eye blepharitis syndrome

Historically, it was widely accepted that the cause of dry eye disease was multifactorial, with overlapping presentations, and separate from blepharitis. It was also believed that anterior blepharitis was unique from posterior blepharitis, and that evaporative dry eye was distinct in its etiology from aqueous insufficiency, according to Rynerson.

He said there is only one underlying ideology common to all of these diseases: blepharitis manifesting itself in a variety of ways.

Images: Hovanesian JA

Rynerson, who is CEO of BlephEx LLC, and co-author Henry D. Perry, MD, attribute a new term to this chronic disease, dry eye blepharitis syndrome (DEBS), in a white paper from Clinical Ophthalmology.

“We, as an industry, didn’t understand the underlying cause and that these different entities all have different symptoms, depending on the stage of disease, which made it confusing,” Rynerson said.

The key to dry eye is the underlying chronic inflammation in the lid margin caused by bacterial virulence factors being produced in a thickening biofilm, which gets more difficult to remove as a patient ages, according to Rynerson.

Once you understand the biofilm, you understand dry eye, he said.

Rynerson and Perry outlined the four lifelong stages for DEBS. Each step corresponds with the amount of accumulated biofilm and what anatomical areas of the lid margin have been encroached.

As soon as normal bacterial flora colonize the lid margin, biofilm will begin to be produced, perhaps as early as 2 months of age, according to Rynerson. However, because it is thin, it causes no problems. In early adulthood, biofilm can accumulate in the lash follicle, leading to folliculitis, which is stage one. Folliculitis can worsen throughout life, eventually leading to lash loss.

Stage two involves inflammation and eventual atrophy of the meibomian gland from an internal accumulation of biofilm and virulence factors, Rynerson said.

“We see this clinically as evaporative dry eye disease, which can occur anywhere from age 20 (contact lens wearers) to age 80,” he said. “The meibomian gland takes longer to affect, simply because it is a larger structure and is more difficult for the biofilm to access than a lash follicle.”

Eventually the biofilm gains access to the lacrimal glands, causing lacrimalitis and aqueous insufficiency, stage three, Rynerson continued.

“This will always occur after meibomian gland disease due to the protected and distant location of the glands of Krause and Wolfring,” he said.

By stage four, inflammation has persisted for so long that there can be a breakdown in the structural integrity of the eyelid, manifesting as ectropion and entropion, Rynerson said. Anywhere the biofilm becomes thick enough for a quorum-sensing gene activation to occur, inflammation can occur.

“Blepharitis can look different in a 40-year-old compared to a 60-year-old compared to an 80-year-old, depending on the thickness of the biofilm and which eyelid structure is affected,” Rynerson said. “The essence of all of the diseases is the same: low-grade chronic, everyday, never-ending, inflammatory damage.”

In nature, all bacteria live in biofilms, which is an impenetrable fortress in which the bacteria thrive, he continued. Biofilms grow virtually everywhere, in almost any environment, from plaque on teeth to glaciers in the poles and around deep-sea vents at the bottom of the ocean.

The biofilm microscopically builds up year after year, layer upon layer. It never willingly disperses, dissolves or sloughs, according to Rynerson. As the biofilm thickens with age, the bacterial counts continue to increase, eventually causing activation of virulence-factor-producing genes. The highly inflammatory virulence factors slowly increase, leading to low-grade chronic disease, explaining the increase in incidence and degree of disease in the aging patient.

“There is only one place on the entire human body that never routinely gets cleaned during our entire life: the eyelid margin,” Rynerson wrote.

Looking to the American Dental Association

The industry should look to the example set by the American Dental Association in improving regular lid hygiene, according to Drs. Hogan, Rynerson and Maharaj.

“[People] will laugh today if you asked if they brushed their teeth. That’s where we need to take lid margin hygiene,” Rynerson said.

More than 100 years ago, no one brushed their teeth daily or practiced any form of regular oral hygiene. After decades of cavities, gingivitis, gum infections and a slew of other oral health problems, teeth would decay, loosen and fall out, he said. Full sets of dentures were commonplace.

“The same thing is going on in the meibomian glands,” Rynerson said. “After 20, 40, 60 years of chronic lid inflammation, we start to lose lid structures, and lashes and meibomian glands get shut down and atrophy. Lacrimal glands get attacked. It’s an exact parallel, plaque is a biofilm.

“If dentistry can effectively treat gingivitis and eventual tooth loss with patient education and regular and routine oral hygiene, why cannot eye doctors effectively treat blepharitis and eventual meibomian gland loss?” Rynerson wrote.

Rynerson foresees routine lid cleaning by an eye doctor on a regular basis in the late 20s or early 30s.

Hogan suggests patient education from a younger age. Her office has a dry eye page on Facebook and dry eye information and products available in office; she even has a dedicated dry eye suite.

The more convenient and affordable the products, the more compliant the patient will be, she noted.

Making the diagnosis

Drs. Hogan, Hovanesian and Maharaj recommend using a validated questionnaire before the examination to highlight important dry eye symptoms and signs.

“By the time a patient sees me, we’ve already uncovered their symptoms, which helps guide the clinical exam,” Maharaj said.

In adults, Hovanesian also recommends screening methods such as the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire for routine administration, even in healthy exams, to identify signs of dry eye. He also suggests a question such as, “How often do your eyes feel dry, gritty, sandy or burning?” and using a response scale of: seldom-never, sometimes, often, never or always.

Schachter said corneal staining is often performed incorrectly, which leads to underdiagnosis.

Hogan utilizes Allergan’s ocular surface disease app on a tablet for patient use, to help gauge symptoms and progress of treatment. Patients go through a full ocular surface evaluation encompassing an oral history, Ocular Surface Disease Index questionnaire, review of symptoms, routine dry eye testing, staining, Schirmer’s and point-of-care testing such as MMP-9 and the TearLab osmolarity test.

“You have to give the dye at least 90 seconds (2 minutes is best), and the staining will look far different,” he said. “That is a large part of why dry eye was underdiagnosed so much. Something as simple as that, correctly staining a cornea.”

Hogan also uses Oculus keratography to visualize the lid, which she said makes it “easy to show the patient and better educate the patient on their condition,” she said.

“You didn’t hear about the role of biofilms and addressing anti-biofilm therapies 5 years ago,” Hogan continued. “We need to look at chronic lid management and lid débridement, as bacteria aren’t always going to respond to antibiotics.”

Maharaj prescreens cataract patients prior to surgery. His team runs them through a dry eye questionnaire, osmolarity testing and meibography, and through this process he has uncovered a lot of disease that is asymptomatic.

“Close to 80% of our pre-cataract dry eye workups are at level 1 dry eye,” he said. “This has been such a game-changer. Patients are leaving more educated and informed.”

Maharaj said practitioners need to start looking for dry eye regularly, and the only tools needed to get started are a slit lamp, fluorescein strip and lissamine strip.

In-office treatment

This year, Maharaj’s practice incorporated intense pulsed light (IPL) therapy, which he finds complementary to the LipiFlow (TearScience). The IPL works on the bacteria and inflammation, and LipiFlow clears the obstructions, he said.

Maharaj also credits Rynerson’s BlephEx device as having a big impact on his practice.

“There is a lot of advanced technology out there, but if you have the basic tools, you’re off to the races and can already make an impact in diagnosing and, therefore, in therapy,” he said.

Maharaj said a Mastrota paddle can be purchased for $100 or less, and with a Q-tip, you can start expressing.

“It can be very daunting, as there is a lot of information out there, but it doesn’t have to be complicated,” he said. “We often get burdened or frightened by technology, but the tools we’ve had since day 1 can be used and employed today. We have the ability to make a difference now.” – by Abigail Sutton

• References:
• Bispo PJM, et al. Pathogens. 2015;doi:10.3390/pathogens4010111.
• Hovanesian JA. Blog: Treat dry eye like glaucoma. February 16, 2016. Healio.com/optometry.
• Hovanesian JA. Blog: Our failing dry eye report card. March 21, 2016. Healio.com/optometry.
• Rynerson JM, Perry HD. Clin Ophthalmol. 2016;10:2455-2467.

• For more information:
• Casey L. Hogan, OD, FAAO, is the owner of Advanced Eye Care Professionals PC, in Oak Lawn, Ill., and can be reached at: chogan6465@aol.com.
• John A. Hovanesian, MD, FACS, is a specialist in cataract, refractive, cornea and pterygium surgery at Harvard Eye Associates in Orange County, Calif., and a PCON Editorial Board member. He can be reached at: johnhova@gmail.com.
• Richard L. Maharaj, OD, FAAO, is the clinical director at eyeLABS Optometry and Center for Ocular Surface Disease and lead optometrist at York-Finch Eye Associates/Humber River Regional Hospital in Toronto, Canada. He can be reached at: rmaharaj@eyelabs.ca.
• James M. Rynerson, MD, is president and CEO of BlephEx LLC in Franklin, Tenn. He can be reached at: docjmrmd@gmail.com.
• Scott Schachter, OD, specializes in ocular surface disease, is in private practice in Pismo Beach, Calif., at Advanced Eyewear and serves as a Vision Source administrator for the central California coast. He can be reached at: applescott@me.com.

Disclosures: Hogan reported no relevant financial disclosures. Maharaj is a speaker for Allergan, Shire, Santen and JJVC – Canada. Rynerson is president and CEO of BlephEx. Hovanesian has financial interest in Allergan, Alcon, Bausch + Lomb, BlephEx, Shire, TearScience and TearFilm Innovations. Schachter serves on the advisory board for Allergan, BlephEx, RySurg, ScienceBased Health, Sun Pharma, and TearScience and is a speaker for Allergan, Bausch + Lomb and BioTissue.