Published in Ocular Surface

Everything That Is Not Dry Eye with Cheat Sheet

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14 min read
Join Nandini Venkateswaran, MD, and Brent Kramer, MD, to review dry eye masqueraders and download the cheat sheet for a deeper dive into the conditions.
In this episode of Interventional Mindset, Nandini Venkateswaran, MD, a fellowship-trained cornea, cataract, and refractive surgeon at Massachusetts Eye and Ear (MEE), sits down with Brent Kramer, MD, a cataract, cornea, refractive, and complex anterior segment surgeon who practices at Vance Thompson Vision to discuss dry eye masqueraders.
The doctors review conditions they have encountered in clinical practice that are common dry eye masqueraders, as well as pearls for appropriately triaging and treating these patients.
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Identifying dry eye masqueraders as corneal specialists

Dr. Kramer noted that corneal specialists are likely to encounter patients with conditions that may present similarly to dry eye since they receive referrals of patients who have been prescribed a multitude of dry eye treatments with no clinical improvements, often requiring further testing and evaluation.
He added that when treating a patient he suspects has ocular surface disease (OSD), he prefers to examine their eye from front to back—starting with the eyelids and ending with the cornea—for a comprehensive assessment of the patient’s ocular surface health.

Download the Dry Eye Masqueraders Cheat Sheet here

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Dry Eye Masqueraders Cheat Sheet

Use this cheat sheet with clinical information on 11 dry eye masqueraders ophthalmologists are likely to encounter in practice for pearls on detecting, diagnosing, and managing the conditions.

Eyelid conditions that can masquerade as dry eye

Nasolacrimal duct obstruction

Dr. Venkateswaran explained that nasolacrimal duct obstruction (NLDO) is one of the first conditions that come to mind as a dry eye masquerader. One of her favorite questions to ask patients to query NLDO is, “Are you tearing? If so, describe what your tears are like.”
The response can help indicate whether an anatomic abnormality may be causing the persistent epiphora. She added that if she observes an asymmetric tear lake, she opts to send the patient for an oculoplastics referral to check for NLDO.

Lid laxity

An additional condition within the spectrum of lid disease that Dr. Venkateswaran has encountered at the clinic is lid laxity. When examining patients, she checks how the eyelid sits against the counter of the globe, particularly in elderly patients experiencing connective tissue changes around the eye.
Dr. Kramer explained that when he’s at the slit lamp examining a patient’s cornea, he always zooms out and assesses the eyelids as well for a thorough evaluation of the patient’s ocular anatomy. Similar to Dr. Venkateswaran, he looks for signs of lid abnormalities such as ectropion, spastic entropion, and patients without a fully-formed tear lake along the tear margin.
When treating patients with lid laxity, Dr. Venkateswaran explained that she often asks if they have sleep apnea. Further, she always everts the upper lid to evaluate the floppiness of the lid and observe the appearance of the superior bulbar conjunctiva, palpebral conjunctiva, and fornix for pathology during a routine eyelid exam.
Of note, lissamine green and fluorescein staining can be helpful in identifying damage to the lower corneal and conjunctival regions, which is often consistent with lagophthalmos.

Giant fornix syndrome

Dr. Kramer described seeing a variety of giant fornix syndrome (GFS) cases ranging in severity, which is a rare but underdiagnosed infectious inflammatory condition of the superior and, less commonly, the inferior conjunctival fornices.1 It is associated with abnormally deep fornices, recurrent bacterial overgrowth of the conjunctiva, and age-related levator aponeurosis degradation.1
When the fornices exhibit significant depth, it can result in a “petri dish” effect where bacterial overgrowth in the eye could lead to increased mucus production and mild conjunctivitis, explained Dr. Kramer. These patients tend to have recurring mucus production and are typically referred in for dry eye or chronic conjunctivitis. In mild cases, he recommends moxifloxacin and prednisolone BID to clear up the bacterial infection.
For more severe forms of GFS, Dr. Venkateswaran mentioned betadine washes and oral antibiotics as approaches to manage bacterial overgrowth. Both Dr. Kramer and Dr. Venkateswaran emphasized that they have encountered the mild form more often, which is often characterized by mucopurulent conjunctivitis.
If a GFS patient is motivated to get off drops and the procedure is indicated, Dr. Kramer has referred these patients to an oculoplastic surgeon to perform a Müllerectomy to shorten the superior fornix.2

Demodex blepharitis

Demodex blepharitis (DB) is a common dry eye masquerader, noted Dr. Kramer, because it can affect such a broad spectrum of patients—in fact, studies have demonstrated that DB accounts for ≥60% of patients with blepharitis.3
The key to identifying DB is to zoom out on the slit lamp and check the eyelid margin for collarettes—the pathognomonic sign of DB. He added that has been pleasantly surprised to see how XDEMVY (lotilaner ophthalmic solution 0.25%, Tarsus Pharmaceuticals) melts away collarettes even without the addition of lid wipes or other lid margin therapies.
Dr. Venkateswaran mentioned that she has become significantly better at detecting and diagnosing the condition with thorough ocular surface exams.
The entire ocular surface exam takes her less than 1 minute and includes:
  1. Having patients look down to check the upper lid margin for collarettes.
  2. Everting the upper lid to assess the upper palpebral conjunctiva for signs of inflammation.
  3. Checking the patient’s meibomian glands for normal meibum secretions.
She remarked that in pediatric patients, she has seen severe DB cause corneal neovascularization, scarring, and corneal perforations. As such, expedient diagnosis and having an effective treatment plan is critical to managing the OSD associated with lid margin disease.

Check out the Dry Eye Masqueraders Cheat Sheet for a deeper dive into the conditions

Conjunctival conditions that can masquerade as dry eye

Conjunctivochalasis (CCH)

Moving further into the eye, Dr. Kramer remarked that another commonly underdiagnosed and undertreated dry eye masquerader is conjunctivochalasis (CCH). Dr. Venkateswaran noted that she mentions CCH to patients when she sees excessive redundant conjunctival folds nasally and temporally, which takes her back to her favorite symptom—excessive tearing.
She then asks the patient to describe how the tears feel in their eye(s). In her professional medical opinion, if patients have multiple areas of CCH, you can often see their tears pool irregularly, which might explain why they describe feeling like their tears pool and eventually just fall out of the eye.

Conjunctival cautery to treat CCH

To manage CCH, Dr. Venkateswaran performs conjunctival cautery by numbing the lower bulbar conjunctiva with either topical Lidogel (lidocaine HCl 2.8% gel) or subconjunctival lidocaine and using a low-temperature thermal cautery and an angled forceps to apply a diffuse superficial injury across the inferior conjunctiva to shrink it.
This is a cost-effective approach that allows surgeons to address the conjunctivochalasis easily with minimal instrumentation, and patients tend to heal in a few weeks with topical steroid eye drops.5 Additionally, she has followed patients many years after the procedure and observed that the CCH generally doesn’t typically recur.
There have been severe cases where she has taken the patient to the operating room (OR) for conjunctival resection and reconstruction with amniotic membrane; however, that is not the case for the majority of the CCH patients at her practice.
When discussing CCH with patients, Dr. Kramer tells patients that in his surgical experience, 50 to 70% of patients see an improvement after conjunctival cautery. He then explains to patients how tears are made in the lacrimal glands, and when tears move across the eye, the CCH acts as a roadblock before they can drain into the punctum and eventually the nose.
Further, if time permits, he provides slit lamp photographs to show patients the changes to their conjunctival anatomy before and after the procedure. He added that he prefers to use high-temperature thermal cautery, and for the sake of convenience for the patient, he has combined this procedure with other intraocular surgeries in the OR setting. Dr Kramer emphasized that he takes the opportunity to treat CCH because, for some patients, it can significantly improve their symptomatology.

CCH and cataract surgery

Subsequently, Dr. Venkateswaran remarked that she has observed a cohort of patients with worsening conjunctivochalasis following cataract surgery. These patients tend to have dry eye complaints, and after cataract surgery, experience persistent foreign body sensation from the CCH.
She has found that performing conjunctival cautery on these patients has been successful in addition to topical immunomodulators or lubrication. She added that this interesting correlation is potentially caused by how the lid speculum is placed during cataract surgery or related to changes in the ocular surface after surgery that alter the overall ocular anatomy.

Corneal conditions that can masquerade as dry eye

Neurotrophic keratitis

Dr. Venkateswaran noted that the most common corneal condition she has encountered that masquerades as dry eye is neurotrophic keratitis (NK). Many times these patients are found to have keratopathy that is recalcitrant to conventional dry eye therapies. These patients can also have other co-morbidities that compound the situation, such as drop toxicity from multiple glaucoma medications, multiple previous ocular surgeries, or prior herpetic keratitis.
The hallmark sign of NK is a disproportionately mild symptomatic response to a severe clinical presentation due to reduced corneal sensitivity, she explained. NK patients tend to have notable staining without being uncomfortable—which is the origin of the classic phrase “stain without pain.”
In her professional medical experience, patients with stage 1 NK tend to have moderate to severe keratopathy and don’t complain about dryness, but instead often describe having blurry vision, which is caused by the keratopathy.
While Dr. Kramer’s practice has a Cochet-Bonnet aesthesiometer, he has found that a cotton swab wisp is generally sufficient to determine if the patient has some form of NK. Additionally, in his clinical experience, whorl keratopathy suggests the patient has NK or limbal stem cell issues.

Treatment options for neurotrophic keratitis

For a stage 1 NK patient who has already been prescribed preservative-free tears, lubricating ointments, and anti-inflammatory medications, Dr. Venkateswaran stated that she would recommend either Oxervate (cenegermin-bkbj ophthalmic solution 0.002% [20mcg/mL], Dompé) or autologous serum tears.
She described having success with both treatments, as Oxyervate is a synthetic nerve growth factor (NGF), which is a key player in NK, and autologous serum drops promote wound healing.6 Further, she expressed appreciation for the fact that she can start patients on one therapy and then transition them to the other depending on the severity of the keratopathy or if symptoms do not improve.
She added that if she is concerned that the patient has severe keratopathy and she wants to intervene before it progresses to stage 2, she may place an amniotic membrane and start them on Oxervate to bridge them successfully between treatments.
Dr. Kramer mentioned that he likes Oxervate because it has a finite treatment window for the treatment of NK, which is critical for dry eye patients who are often prescribed a multitude of concurrent therapies that can worsen compliance.
Additionally, Dompé has made efforts to make Oxervate more accessible to patients. Dr. Venkateswaran noted that Dompé has patient education resources that describe the process of preparing and instilling Oxervate to improve treatment understanding and adherence.

Conclusion

Corneal specialists are in a unique position to detect and treat dry eye masqueraders, as they often receive referrals of patients with recalcitrant dry eye symptoms that require further testing.
From the eyelids to the corneal nerves, ophthalmologists can uncover dry eye masqueraders by:
  • Asking patients about the quality of their tears to identify NLDO and CCH
  • Zooming out from the cornea during slit lamp examinations to evaluate the eyelids for:
    • Demodex collarettes
    • Lid laxity
    • Loose or redundant conjunctival folds caused by CCH
  • Checking patients with chronic conjunctivitis for GFS
  • Assessing corneal sensitivity with a cotton swab wisp in patients suspected of having NK

Before you go, download the Dry Eye Masqueraders Cheat Sheet

  1. Moshirfar M, Kay WC, Ronquillo Y. Giant Fornix Syndrome. In: StatPearls. Treasure Island (FL): StatPearls Publishing; July 18, 2023.
  2. Jones D, Lyle CE, Fleming J. Superior Conjunctivoplasty-Mullerectomy for Correction of Chronic Discharge and Concurrent Ptosis in the Anophthalmic Socket with Enlarged Superior Fornix. Ophthalmic Plast Reconstr Surg. 2010;26(3):172-175. doi:10.1097/IOP.0b013e3181b8c49a
  3. 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;49(8):311-318. doi:10.1097/ICL.0000000000001003
  4. XDEMVY Prescribing Information. Tarsus Pharmaceuticals. Published July 2023. Accessed May 30, 2024. https://tarsusrx.com/wp-content/uploads/XDEMVY-Prescribing-Information-24JUL23.pdf.
  5. Allen RC. Conjunctival Cautery for Conjunctivochalasis. American Academy of Ophthalmology. Published December 14, 2023. Accessed May 30, 2024. https://www.aao.org/education/clinical-video/conjunctival-cautery-conjunctivochalasis.
  6. Venkateswaran N, Dang V. Everything You Need to Know About Autologous Serum Eye Drops. Eyes On Eyecare. Published April 17, 2024. Accessed May 30, 2024. https://eyesoneyecare.com/resources/everything-you-need-to-know-autologous-serum-eye-drops/.
Nandini Venkateswaran, MD
About Nandini Venkateswaran, MD

Dr. Nandini Venkateswaran is a member of the Cornea and Refractive Surgery Service at Massachusetts Eye and Ear and an Assistant Professor of Ophthalmology at Harvard Medical School. She is a fellowship-trained cataract, cornea and refractive surgeon.

Dr. Venkateswaran earned her medical degree with a distinction in community health from the University of Rochester School of Medicine and Dentistry, where she was inducted into the Alpha Omega Alpha medical honor society. She completed her Ophthalmology residency at the Bascom Palmer Eye Institute/University of Miami, after which she completed a fellowship in cornea, external disease and refractive surgery at Duke University.

She specializes in complex cataract surgery with use of premium lens technologies, refractive surgery (LASIK/PRK/SMILE/ICL/RLE), corneal crosslinking and transplantation as well as ocular surface disease.

Nandini Venkateswaran, MD
Brent Kramer, MD
About Brent Kramer, MD

Brent Kramer, MD, is an anterior segment surgeon who works at Vance Thompson Vision in Sioux Falls, SD, and Alexandria, MN. He is a diehard Tarheel fan who completed his cornea fellowship at Duke University and also made pitstops at South Dakota State, the University of Iowa, and UNC along the way.

When he's not doing surgery, he loves spending time with his wife, two kids, and two Vizsla puppies.

Brent Kramer, MD
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