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Corneal basement membrane dystrophy: Dry eye disease’s sticky wicket
Consider this sneaky condition in patients who have a healthy tear film but still experience discomfort.
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Our severe dry eye disease archetype, “Linda Blair,” has come to your office with her eyes aflame and her head a-spinning. She has marched into your exam room spewing horrific invective at any and all who sat on the other end of your Haag-Streit, but you were prepared. You read all three parts of our series on starting and building a dry eye practice, and you went all the way and put into place the advanced dry eye protocol along with your entire staff.
When Linda arrived, you evaluated her with tear osmolarity (elevated), MMP-9 inflammation testing (positive) and even a Schirmer (inconclusive). Your bravest tech held her head still so that you could do LipiView (low oil/never, ever blinks) and obtain meibomian gland imaging (mostly burned out ... get it?). Your next bravest tech held her in the slit lamp (tech No. 1 was now possessed) so that you could determine that she had a tear breakup time of 4 and diffuse superficial punctate keratitis.
Once you acquired all of your data, a care plan took shape. Linda was placed on your favorite treatment for inflammatory DED, Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan) or Xiidra (lifitegrast ophthalmic solution 5%, Shire), mega-doses of re-esterified fish oil and an oil-based artificial tear like Retaine MGD (OcuSoft). This initial regimen improved her symptoms enough that she was able to sit by herself through a LipiFlow (TearScience) treatment session (good thing — with two techs now possessed, you were running out of help). A few weeks later the demonic specter of The Exorcist is nowhere to be seen. On follow-up examination, Linda now has a tear breakup time of 8, no superficial punctate keratitis, an osmolarity of 302 in each eye, and a barely registering InflammaDry (RPS). She seems almost happy, except for one thing: Linda still has pain.
Underlying cause of pain
This is an all-too familiar scenario for those of us who treat severe DED. Your patient has diligently followed all of your instructions, and your treatment program has resulted in massive improvements in pretty much everything you can measure, including symptoms. Yet for all of that, there is still a nagging, ever-present discomfort. Sometimes it is an aching sensation, and at other times it is sharp. Despite all of your apparent success this discomfort remains, rocking the psyche and shaking the confidence of your otherwise happier patient. A quick trip back to the slit lamp is likely to reveal the culprit. The silent, stealthy enemy underlying the pain is very often corneal basement membrane dystrophy (BMD).
Sometimes it takes a time or three looking at your patient for BMD to register in your consciousness. Try not to feel too badly about that. There is so much to look at and think about in a complex DED patient that oftentimes we look right past the obvious. It has certainly happened to me more than once. Common things are common, and they certainly can be present along with other common things. Like DED and BMD. The longer I treat DED, and the more patients I see with both DED and BMD, the more it has become evident that BMD is responsible for many more symptoms than I recall learning about in my residency training.
Also known as map/dot/fingerprint dystrophy, BMD is an abnormality of the basement membrane underlying the corneal epithelium. There are probably multiple genetic variants. Sheets of basement membrane curl and bunch upon themselves. Sometimes tiny nests of epithelial cells become entrapped in these sheets. This all, in turn, creates an uneven epithelial surface. I like to describe the outer layer of the cornea as “rumply and bumply” to my patients. Even an otherwise perfectly healthy tear film can be challenged to lubricate both the peaks and the valleys of the corneal surface.
Dryness from lack of lubrication of any type causes inflammation. The underside of the epithelium typically attaches to the top of the basement membrane much like the loops and hooks of Velcro. In a patient with BMD this is often more like the connection between a tire and the road on a stormy night: The corneal epithelium is “hydroplaning” on its basement membrane and susceptible to both micro- and macro-erosions. These erosions are probably responsible for the scarring we can see in late-stage BMD, as well as inflammation.
Diagnosis and treatment
Making the diagnosis of BMD can be pretty tricky. For sure there are cases that fairly jump through the slit lamp right into your brain, but I am always impressed by how subtle the diagnosis can be. On occasion, something your patient says might prompt you to bump up the magnification on the slit lamp, letting you see the faintest of irregularities just under the epithelial surface. More often than not I pick up the subtle cases after I have instilled fluorescein dye and cranked up my cobalt blue filter. Sometimes there is a tiny area of barely elevated, speckled staining. However, the most common “tell” is what I have come to call “ghost staining”: an area of normal fluorescence that surrounds a relatively dark space. The presence of multiple ghost stains is probably pathognomonic for BMD.
Once we identify our nemesis, how should we go about treating the discomfort that is caused by BMD? Job No. 1, as you have already done for Linda, is to maximize the health of the tear film. Having accomplished that, if you elicit a history of discomfort that is more prominent in the morning, treatment for a presumed micro-erosion with hypertonic saline ointment could be tried. A very logical, and in my opinion vastly underutilized, option is to prescribe a topical NSAID. The best of these for this indication is one of the versions of bromfenac. Given the outstanding track record of DuraSite (InSite Vision) in the setting of ocular surface disease, I am particularly looking forward to having BromSite (bromfenac ophthalmic solution 0.075%, Sun Pharma) available for these patients.
What if none of this works and you are still convinced that BMD is the cause of the recalcitrant discomfort? At this point you are more than justified to be aggressive and to try to surgically alter the basement membrane/epithelial junction. Are there discrete areas that look like they are repeatedly eroding or appear to be difficult to lubricate “bumples?” Go ahead and perform micro-puncture of the epithelium with your YAG laser. (Use a needle? In this age of femtosecond laser surgery for 0.37 D cylinder? Please.) If the entire cornea is just one massive landscape littered with ghost staining, consider a wide epithelial debridement. The ultimate treatment (for those of you old enough to remember the earliest days of laser vision correction) is phototherapeutic keratectomy, in which the basement membrane is smoothed by the excimer laser. It is not typically paid for by insurance, but the last time I checked, the PTK key card is free. Go ahead and give it away. Doing so will make both you and your patient feel good.
Corneal basement membrane dystrophy is sneaky. Be on the lookout for it in those patients with a healthy tear film who are still uncomfortable.
- For more information:
- Darrell E. White, MD, can be reached at SkyVision Centers, 2237 Crocker Road, Suite 100, Westlake, OH 44145; email: dwhite@healio.com.
Disclosure: White reports he is a consultant for Bausch + Lomb, Allergan, Shire and Eyemaginations; is on the speakers board for Bausch + Lomb, Allergan and Shire; and has a financial interest in TearScience.