Published in Ocular Surface

Is It Dry Eye Or Not?

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11 min read

Discover how optometrists can identify and manage five common ocular surface conditions with similar symptoms to dry eye.

Is It Dry Eye Or Not?
Dry eye disease is an important clinical consideration when caring for patients. The prevalence of dry eye disease is believed to be 11.66% for patients 50 years and older.1
It is an increasing component of the comprehensive optometrist’s practice as it affects several areas, including corneal and conjunctival health, visual quality, and symptoms of discomfort.
Advances in technology have provided us opportunities to better diagnose and treat this prevalent condition. Saying that, it is critical to appropriately differentiate it from other ocular surface conditions that can present with similar symptoms.
Here we will look at five common conditions that are important to differentiate from dry eye disease (DED).

Five common dry eye masqueraders

1. Epithelial basement membrane dystrophy (EBMD)

Epithelial basement membrane dystrophy (EBMD) is a condition in which aberrant corneal epithelial attachments to the underlying basement membrane create elevated areas in the cornea. The basement membrane is highly irregular and extends into the epithelial tissue, which is thought to be part of the reason for the irregular corneal surface.2
Depending on the location of corneal irregularities, these patients may present with symptoms of blurry vision or vision that fluctuates. Additionally, these individuals may have ocular discomfort that mimics symptoms of dry eye.

Treatment for EBMD

Treatment for these individuals will often depend on the amount of symptoms that these patients present with. In mild cases, consider artificial tears or lubricants for the ocular surface.
If these patients have concurrent recurrent corneal erosions, appropriate treatment needs to be considered to help reduce the risk of recurring events, including phototherapeutic keratectomy, corneal debridement, and the use of amniotic membranes.3
For patients whose vision is affected by the condition, a rigid lens such as a corneal gas permeable lens, a hybrid lens, or a scleral lens can provide visual benefits. Additional treatment to renormalize the corneal surface may include corneal debridement or phototherapeutic keratectomy.

Staining in patients with EBMD

Be cautious when viewing these patients' eyes with fluorescein stain, a cobalt blue light, and a Wratten #12 filter, as these elevated epithelial areas can appear similar to areas of reduced tear film breakup.
The key differentiator is that the negative staining present with EBMD is always on the same part of the cornea after the blink while tear film breakup will oftentimes be in different regions of the cornea.
Figure 1 is an example of a large region of negative staining secondary to EBMD.
EBMD Staining
Figure 1: Courtesy of Mile Brujic, OD, FAAO.
Figure 2 illustrates a dry eye patient with severely reduced tear film breakup time.
Dry Eye Staining
Figure 2: Courtesy of Mile Brujic, OD, FAAO.

2. Floppy eyelid syndrome

Floppy eyelid syndrome (FES) is a condition in which low elastin levels in the eyelids create a loose eyelid apposition to the globe. As such, it creates a situation in which lid eversion can easily occur. This can be easily seen during slit lamp evaluation and attempted lid eversion, as these patients have very little elastic resistance when eversion is performed.4
In the evening, these patients can have spontaneous eversion, creating exposure of the palpebral and bulbar conjunctival surface along with the cornea. This can cause several signs and symptoms that mimic the dry eye patient. By everting the lid during the slit lamp evaluation, you can rule out this condition as the potential cause for the patient's ocular discomfort.

Treatment for floppy eyelid syndrome

The treatment for FES initially includes simply making sure that the eyelids do not evert in the evening. This can be accomplished in several ways, including a sleep mask, goggles, and taping the lids shut with either medical grade tape or SleepTite/SleepRite (Ophthalmic Resources Partners).5
Additionally, these patients may benefit from ointments applied to the ocular surface in the evening or before bed to protect the ocular surface by reducing friction and the subsequent papillary reaction due to the mechanical rubbing often observed in DED.5
In more severe cases or for those intolerant of the previous treatments, an eyelid resection may be warranted to tighten the eyelids' relationship with the globe.6

The link between FES and sleep apnea

It is important to understand the strong association between FES and obstructive sleep apnea. Sometimes, these patients may already be diagnosed with sleep apnea and simply didn’t think about discussing this with us. If they are not diagnosed, sleep studies are recommended to rule out sleep apnea.
Left undiagnosed and untreated, patients with this condition run the risk of developing retinal vein occlusion, non-arteritic anterior ischemic optic neuropathy (NAION), heart attack, stroke, cardiac arrhythmia, and congestive heart failure.7
Figure 3 illustrates the excessive lid laxity present in patients with FES.
Floppy Eyelid Syndrome
Figure 3: Courtesy of Cory J. Lappin, OD, MS, FAAO.

3. Incomplete lid seal

In a normal individual, when the eyelids close, the upper and lower eyelids create a seal that holds the moisture on a patient's ocular surface. When the normal interaction of the eyelids is disrupted, and an adequate lid seal is not present, it can create small levels of exposure.

Testing for incomplete lid seal

An easy test to perform in-office is the Korb-Blackie light test. The test is performed by placing a transilluminator against the relaxed, closed, outer upper eyelids of semi-reclined patients.
The amount of visible light emanating from the lid area between the lashes is then graded. In a patient with an incomplete lid seal, the light will pass through where the upper and lower eyelid meet.8

Treatment for incomplete lid seal

These patients will oftentimes complain of eye dryness symptoms in the morning.9 Treatment includes protecting the ocular surface from exposure. Ointments in the evening can be helpful for these patients.
Additionally, sleep masks and goggles, such as Eyeseals 4.0 (EyeEco/PRN Vision Group), and taping the lids shut with either medical grade tape or SleepTite/SleepRite, can help reduce the evaporative effects related to incomplete lid closure in the evening for these patients.
To learn more about ocular surface conditions that can masquerade as dry eye, check out the article Everything That Is Not Dry Eye and download the cheat sheet!

4. Neurotrophic keratitis

Neurotrophic keratitis is a condition in which the nerve plexus within the cornea, or at any point along the trigeminal sensory pathway from which it arises, is altered, creating a poorly innervated ocular surface.
The impairment of sensory innervation causes a reduction in the lacrimation reflex and the vitality, metabolism, and mitosis of epithelial cells, with a subsequent deficiency in epithelial repair, and abnormal development of the basal lamina.10,11,12,13,14
However, due to the lack of corneal sensation, these patients will oftentimes not have significant discomfort. This is often referred to as “stain without pain” indicating that corneal staining is present without the perception of the typical pain we would expect these patients to have.

Testing for neurotrophic keratitis

It is important to diagnose these patients and not misdiagnose them as dry eye patients. The diagnosis of neurotrophic keratitis is made through corneal sensitivity testing, which can be performed by using a Cochet-Bonnet aesthesiometer or the end of a cotton-tipped applicator made into a wisp, which is then touched against the corneal surface.
If the patient cannot feel the implement touch the surface, or there is reduced sensation, this is indicative of neurotrophic keratitis.11,12,13,14
Figure 4 demonstrates corneal sensitivity testing being performed with a cotton wisp.
Corneal Sensitivity Testing
Figure 4: Courtesy of Cory Lappin, OD, MS, FAAO.

Treatments for neurotrophic keratitis

Ocular lubricants are oftentimes recommended for these patients, but very rarely utilized compliantly because of the lack of traditional dry eye symptoms. However, topical lubrication alone does not address the underlying nerve dysfunction and more advanced treatments are typically necessary.
Treatment for these patients may include a temporary application of an amniotic membrane.15 Additionally, Oxervate (cenegermin-bkbj ophthalmic solution 0.002% [20mcg/mL], Dompé US), a recombinant form of neurotrophic growth factor (NGF) that is structurally identical to endogenous NGF, is available for these patients as well and is FDA-approved as a drop used six times a day for a 2-month course.16

5. Demodex blepharitis

In our efforts to identify the underlying reason for symptoms a patient may be experiencing, we oftentimes overlook the lid margin as a contributory factor. Be cautious not to miss the presence of collarettes at the base of the lashes.
This is a pathognomonic sign associated with Demodex overpopulation in the lash follicles.17 It is important to identify the presence of collarettes in patients with symptoms of dry eye as they present with similar symptoms.
Figure 5 offers a high-magnification view of collarettes at the base of the eyelashes.
Demodex Blepharitis
Figure 5: Courtesy of Mile Brujic, OD, FAAO.

Treatment for Demodex blepharitis

We have traditionally treated this in a number of ways including lid hygiene, tea tree oil, and microblepharoexfoliation.17
Recently, a pharmaceutical agent was FDA-approved for the treatment of Demodex blepharitis in the form of Xdemvy (lotilaner ophthalmic solution 0.25%, Tarsus Pharmaceuticals), which is dosed twice a day for 6 weeks.

In conclusion

There are several conditions that masquerade as dry eye in both the symptoms that a patient will experience in addition to the signs that they present with.
It is critical to identify these conditions in order to differentiate them from dry eye and provide appropriate therapy for these patients.
  1. Dana R, Bradley JL, Guerin A, et al.  Estimated Prevalence and Incidence of Dry Eye Disease Based on Coding Analysis of a Large, All-age United States Health Care System. Am J Ophthalmol. 2019 Jun:202:47-54.
  2. Bozkurt B, Irkec M. In vivo laser confocal microscopic findings in patients with epithelial basement membrane dystrophy. Eur J Ophthalmol. 2009 May-Jun;19(3):348-54.
  3. Yeu E, Hashem O, Sheha H. Treatment of Epithelial Basement Membrane Dystrophy to Optimize the Ocular Surface Prior to Cataract Surgery. Clin Ophthalmol. 2022;16:785-795. Published 2022 Mar 15. doi:10.2147/OPTH.S356421
  4. Salinas R, Puig M, Fry CL, et al. Floppy eyelid syndrome: A comprehensive review. Ocul Surf. 2020 Jan;18(1):31-39.
  5. De Grogorio A, Cerini A, Scala A, et al. Floppy eyelid, an under-diagnosed syndrome: a review of demographics, pathogenesis, and treatment. Ther Adv Ophthalmol. 2021;13:25158414211059247. Published 2021 Dec 5. doi:10.1177/25158414211059247
  6. Ezra DG, Beaconsfield M, Sira M, et al. Long-term outcomes of surgical approaches to the treatment of floppy eyelid syndrome. Ophthalmology. 2010;117(4):839-846. doi:10.1016/j.ophtha.2009.09.009
  7. Kloosterboer A, Negron CY, Stokkermans TJ. Floppy Eyelid Syndrome. In: StatPearls. Treasure Island (FL): StatPearls Publishing; April 19, 2023.
  8. Blackie CA, Korb DR. A novel lid seal evaluation: the Korb-Blackie light test. 2015 Mar;41(2):98-100.
  9. Kenrick C. Morning dry eye may be caused by incomplete lid seal. Healio. Published January 4, 2018.
  10. Semeraro F, Forbice E, Romano V, et al. Neurotrophic keratitis. Ophthalmologica. 2014;231(4):191-7.
  11. Bonini S, Rama P, Olzi D, Lambiase A. Neurotrophic keratitis. Eye (Lond). 2003;17(8):989-995. doi:10.1038/sj.eye.6700616
  12. Mastropasqua L, Massaro-Giordano G, Nubile M, et al. Understanding the Pathogenesis of Neurotrophic Keratitis: The Role of Corneal Nerves. J Cell Physiol. 2017;232(4):717-724. doi:10.1002/jcp.25623
  13. Norn MS. Measurement of sensitivity. In: Norn MS (ed). External Eye Diseases. Methods of Examination. Copenhagen, Denmark: Munksgaard International Publisher Ltd; 1974.
  14. Faulkner WJ, Varley GA. Corneal diagnostic technique. In: Krachmer JH, Mannis MJ, Holland EJ (eds). Cornea: Fundamentals of Cornea and External Disease. St Louis, MO, USA: Mosby; 1997; 275–281.
  15. Sacchetti M, Lambiase A. Diagnosis and management of neurotrophic keratitis. Clin Ophthalmol. 2014;8:571-579.
  16. Voelker R. New drug treats rare, debilitating neurotrophic keratitis. JAMA. 2018;320(13):1309.
  17. Rhee MK, Yeu E, Barnett M, et al. Demodex Blepharitis: A Comprehensive Review of the Disease, Current Management, and Emerging Therapies. Eye Contact Lens. 2023 Aug 1;49(8):311-318.
Mile Brujic, OD, FAAO
About Mile Brujic, OD, FAAO

Mile Brujic, OD, FAAO is a 2002 graduate of the New England College of Optometry. He is a partner of Premier Vision Group, a successful four location optometric practice in Northwest Ohio. He practices full scope optometry with an emphasis on ocular disease management of the anterior segment and specialty contact lenses. He is active at all levels of organized optometry. Dr. Brujic is on the editorial board for a number of optometric publications. He has published over 400 articles and has given over 1800 lectures, both nationally and internationally on contemporary topics in eye care.

Mile Brujic, OD, FAAO
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