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Presentation

A 62-year-old Asian female presented with chief complaints of blurry vision, mild burning, redness, watery eyes, and slight pain. She reported that her symptoms were worse on windy days and she regularly woke up at night to put drops in. She had been diagnosed with severe dry eye, and her medical history was significant for Sjögren’s syndrome (8 years), rheumatoid arthritis, and mixed connective tissue disorder.

The patient had previously been given moisture retention goggles and punctal plugs to treat her dry eyes. At the time of presentation, her ocular medications included topical cyclosporine 0.05%, a dual acting mast cell stabilizer/antihistamine agent as needed, topical corticosteroid, and preservative-free artificial tears to be taken hourly in both eyes. She was also taking systemic medications, including the anti-inflammatories naproxen, hydroxychloroquine, and prednisone, plus oral pilocarpine for her dry mouth, and medications for hypertension (atenolol and amlodipine) and allergy (fluticasone and loratadine).

Based on the patient’s history and presentation, what do you think I immediately suspected as the primary cause of her symptoms?

 
a. Dry eye
Yes. It is common for dry eye patients to have primarily vision complaints.1 Vision disturbances in dry eye such as episodes of blurred vision are thought to be associated with tear film instability and corneal surface irregularity.1 Although burning, redness, watery eyes, and pain are nonspecific ocular surface symptoms, exacerbation of such symptoms by environmental factors such as wind is a characteristic sign of dry eye. In addition, the patient’s previous diagnosis of dry eye and long history of Sjögren’s syndrome and other autoimmune diseases all point toward a diagnosis of Sjögren’s syndrome-related dry eye.
  1. Goto E, Yagi Y, Matsumoto Y, Tsubota K. Impaired functional visual acuity of dry eye patients. Am J Ophthalmol. 2002;133:181-6.
 
b. Allergic conjunctivitis
Please select again. Although the patient may have had ocular allergy, I did not consider this her primary problem.
 
c. Infectious keratitis
Please select again. This was not my impression. Infectious keratitis is typically unilateral; and the patient’s history was not consistent with corneal infection.
 
d. Anterior uveitis
Please select again. Typical symptoms of anterior uveitis include photophobia, pain, and decreased vision. This patient’s presenting complaints and ocular history suggest an etiology other than inflammation of the anterior uvea.
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Examination

The patient’s uncorrected visual acuity was 20/25 OD and 20/30 -2 OS. External evaluation showed bilateral meibomian gland dysfunction (MGD) and a punctal plug OD (missing plug OS). Anterior segment evaluation showed conjunctival injection, conjunctivochalasis, and diffuse punctate epithelial keratopathy across the entire corneal surface of both eyes.

Tear osmolarity measured 333 mosm/L OD and 287 mosm/L OS. Testing for matrix metalloproteinase-9 found elevated levels. Tear film breakup time was 2-3 seconds, and Schirmer test results were 2mm OD, 3mm OS.

These results support a diagnosis of poorly controlled Sjögren’s syndrome-associated dry eye. Notably, the patient was not experiencing significant pain despite the advanced state of her disease.

What do you think might explain the absence of significant burning and foreign body sensation, which are common complaints in patients with the Sjögren’s syndrome-associated severe dry eye?

 
a. MGD
Please select again. I did not consider this a likely explanation. MGD is frequently found in patients with Sjögren’s syndrome, contributing to dry eye symptoms and ocular surface changes through excessive evaporation and tear film instability.1 MGD would likely increase rather than ameliorate symptoms.
  1. Shimazaki J, Goto E, Ono M, et al. Meibomian gland dysfunction in patients with Sjögren syndrome. Ophthalmology. 1998;105(8):1485-8.
 
b. Punctate epithelial keratopathy
Please select again. Punctate epithelial keratopathy is a common form of ocular surface damage often seen in cases of tear hyperosmolarity and ocular surface inflammation. That said, I do not think epitheliopathy explains the absence of pain symptoms.
 
c. Corneal hypoesthesia
Yes. Corneal hypoesthesia—reduced corneal sensation—has been observed in patients with chronic dry eye.1 Those with Sjögren’s syndrome may exhibit corneal hypoesthesia to even a greater extent due to more severe corneal nerve damage. 2 Indeed, Sjögren’s syndrome patients with extensive corneal staining usually have fewer dry eye symptoms than those with less corneal stain, and this discrepancy between objective signs and subjective symptoms has been attributed to the loss of corneal sensation.2,3 In this patient’s case, the neurotrophic state of the cornea probably explains why dry eye manifested itself largely through vision disturbances rather than through significant symptoms of discomfort.
  1. Bourcier T, Acosta MC, Borderie V, et al. Decreased corneal sensitivity in patients with dry eye. Invest Ophthalmol Vis Sci. 2005;46(7):2341-5.
  2. Han SB, Hyon JY, Wee WR, et al. Reduced corneal sensitivity in patients with primary Sjögren's syndrome. Acta Ophthalmol. 2010;88(7):277-8.
  3. Adatia FA, Michaeli-Cohen A, Naor J, Caffery B, et al. Correlation between corneal sensitivity, subjective dry eye symptoms and corneal staining in Sjögren's syndrome. Can J Ophthalmol. 2004;39(7):767-71.
 
d. Conjunctivochalasis
Please select again. This is an unlikely the explanation. The presence of conjunctivochalasis can contribute to pathogenesis of dry eye and exacerbate dry eye symptoms.1
  1. Di Pascuale MA, Espana EM, Kawakita T, et al. Clinical characteristics of conjunctivochalasis with or without aqueous tear deficiency. Br J Ophthalmol. 2004;88(3):388-92.
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Treatment Symptom Relief

The first goal of treatment for moderate to severe dry eye is to relieve symptoms and restore ocular comfort. This patient’s symptomatic complaints, along with tear hyperosmolarity in the right eye and signs of ocular surface damage, indicated that she needed additional treatment.

On top of the preservative-free artificial tear drop the patient was already using, I prescribed LACRISERT® (hydroxypropyl cellulose ophthalmic insert), which acts to lubricate the eye and is indicated to treat moderate to severe dry eye.1

  1. Koffler BH, McDonald M, Nelinson D. Improved signs and symptoms and quality of life with dry eye syndrome: hydroxypropyl cellulose ophthalmic insert patient registry. Eye Contact Lens. 2010;3:170-6.

 

In addition to its lubricating effect and efficacy in symptom relief, what features of LACRISERT® (hydroxypropyl cellulose ophthalmic insert) do you think I considered particularly beneficial for this patient?

 
a. Once-a-day dosing (some patients may require twice-a-day dosing)
Please select again. Yes. The patient had been expected to use artificial tears once every hour. LACRISERT® inserts are typically placed once daily.1 What other features of LACRISERT may benefit this patient?
  1. Lacrisert [package insert] Bridgewater, NJ: Valeant Pharmaceuticals International, Inc.; 2014.
 
b. Continuous ocular surface protection
Please select again. Yes. The polymer slowly released from LACRISERT® can thicken and stabilize the tear film, allowing it to remain on the ocular surface longer to help protect the surface.1 What other features may be beneficial in this case?
  1. Lacrisert [package insert] Bridgewater, NJ: Valeant Pharmaceuticals International, Inc.; 2014.
 
c. Safety
Please select again. This was not a particular concern in this case.
 
d. Both a and b
Yes. In most cases, LACRISERT® requires application of only one insert each day; some patients may require twice daily use for optimal results. Because LACRISERT dissolves slowly, it is dosed once daily and acts to lubricate and protect the eye over that time period. This can be beneficial for patients with severe dry eye from Sjögren’s syndrome. These patients typically have a highly desiccated ocular surface and defective corneal sensation, which was the case with this patient. The reduced corneal sensation in these cases means that one important cue for taking a drop is missing. Reduced corneal sensitivity due to severe ocular dryness may impact drop usage, as these patients may delay application of artificial tears until vision disturbances occur, leaving the ocular surface at risk for further damage. To be proactive about helping to prevent such damage, I encourage use of LACRISERT in all my Sjögren’s syndrome patients with moderate to severe dry eye.
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Treatment Other Considerations

Besides improvement of subjective symptoms, one important component of dry eye treatment is restoring the ocular surface, including improving tear film integrity and homeostasis.

What else do you think I counseled the patient to do to improve her condition?

 
a. Continue with topical cyclosporine 0.05%
Please select again. Yes. Topical cyclosporine has been shown to increase tear production, which can improve signs and symptoms in patients with moderate-to-severe dry eye.1 What else may help improve the patient’s condition?
  1. Sall K, Stevenson OD, Mundorf TK, et al. Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease. CsA Phase 3 Study Group. Ophthalmology. 2000;107(4):631-9.
 
b. Discontinue use of oral pilocarpine
Please select again. I did not instruct the patient to stop using oral pilocarpine. Acting on salivary glands to stimulate saliva production, oral pilocarpine is approved for treatment of dry mouth in Sjögren’s syndrome. Pilocarpine can also stimulate tear secretion, albeit to a less degree than saliva secretion.1
  1. Vivino FB, Al-Hashimi I, Khan Z, et al. Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with Sjögren syndrome: a randomized, placebo-controlled, fixed-dose, multicenter trial. P92-01 Study Group. Arch Intern Med. 1999;159(2):174-81.
 
c. Discontinue use of loratadine
Please select again. Yes. Ocular dryness can occur with use of common oral antihistamines.1 Discontinuing use of oral loratadine eliminates one potential contributor to ocular dryness. What else may help improve the patient’s condition?
  1. Ousler GW, Wilcox KA, Gupta G, et al. An evaluation of the ocular drying effects of systemic antihistamines: loratadine and cetirizine hydrochloride. Ann Allergy Asthma Immunol. 2004;93:460-4.
 
d. Both a and c
Yes. Inflammation is a key element of the pathogenesis of Sjögren’s syndrome dry eye and a fundamental mechanism underlying dry eye symptoms and associated ocular surface damage.1 Topical cyclosporine has been shown to increase tear production in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca.2 On the other hand, oral antihistamines such as loratadine have drying effects on the eye3; use of such medications should be minimized or avoided altogether in patients with severe dry eye.
  1. Stevenson W, Chauhan SK, Dana R. Dry eye disease: an immune-mediated ocular surface disorder. Arch Ophthalmol. 2012;130(1):90-100.
  2. Sall K, Stevenson OD, Mundorf TK, et al. Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease. CsA Phase 3 Study Group. Ophthalmology. 2000;107(4):631-9.
  3. Ousler GW, Wilcox KA, Gupta G, et al. An evaluation of the ocular drying effects of systemic antihistamines: loratadine and cetirizine hydrochloride. Ann Allergy Asthma Immunol. 2004;93:460-4.
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First Follow-up

 

The patient returned for follow-up in 3 weeks.

What do you think I focused on during the patient’s first follow-up visit?

 
a. The patient’s experience with and ability to handle LACRISERT® (hydroxypropyl cellulose ophthalmic insert)
Yes. For patients to benefit from LACRISERT® therapy, they must use the insert properly. In order for them to insert properly, it is imperative that I train them. Proper placement of the insert is my first concern during follow-up, even though it is not a problem for most patients, including those with rheumatoid deformity in their hand.1 I eventually repeat the diagnostic tests such as measurement of tear osmolarity but only at some point after I am assured that the patient has been doing well with the insert.
  1. Hill JC. Slow-release artificial tear inserts in the treatment of dry eyes in patients with rheumatoid arthritis. Br J Ophthalmol. 1989;73(2):151-4.
 
b. Changes in the patient’s vision
Please select again. This was not my main concern for the first follow-up, although I did expect the patient’s vision to improve with long-term LACRISERT® therapy
 
c. Tear osmolarity changes
Please select again. I did plan to repeat measurement of tear osmolarity to assess dry eye status and treatment efficacy, but not as soon as the first follow-up visit.
 
d. Ocular surface evaluation
Please select again. There is no treatment that would lead me to expect rapid improvement of the ocular surface in advanced Sjögren’s syndrome dry eye.
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Additional Recommendations

 

At the follow-up, the patient reported no problem with the use of LACRISERT® (hydroxypropyl cellulose ophthalmic insert). I instructed her to continue with the therapy, along with the other aspects of her regimen. Additionally, I introduced and discussed advanced dry eye treatments with the patient, telling her that we were holding them in reserve for use should her condition warrant. These include autologous serum drops and amniotic membrane placement.

Many patients with Sjögren’s syndrome will have to consider such advanced therapies as their ocular condition progresses. Because initiating these types of treatments can be a particular challenge in this patient population, I find it extremely helpful to introduce potential follow-on therapies at an early point. Regardless of efficacy, each of these therapies has its own challenges. An amniotic membrane placement will blur vision for a while; autologous serum will require the patient to be vigilant about its storage. Having an early discussion makes patients aware of their options and prepares them to incorporate such treatments if and when the time comes.

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Douglas K. Devries, OD

Douglas K. Devries, OD Co-founder and managing partner of Eye Care Associates of Nevada and serves as both clinical director and optometric residency program director for the state-wide practice. He is an adjunct clinical professor of optometry at Pacific University and serves on the advisory board or speakers' bureau of Bausch + Lomb.

Indications and Usage

LACRISERT® (hydroxypropyl cellulose ophthalmic insert) is indicated in patients with moderate to severe dry eye syndromes, including keratoconjunctivitis sicca. LACRISERT® is indicated especially in patients who remain symptomatic after an adequate trial of therapy with artificial tear solutions. LACRISERT® is also indicated for patients with exposure keratitis, decreased corneal sensitivity, and recurrent corneal erosions.

Important Safety Information

  • LACRISERT® (hydroxypropyl cellulose ophthalmic insert) is contraindicated in patients who are hypersensitive to hydroxypropyl cellulose.
  • Instructions for inserting and removing LACRISERT® should be carefully followed.
  • If improperly placed, LACRISERT® may result in corneal abrasion. Because LACRISERT® may cause transient blurred vision, patients should be instructed to exercise caution when driving or operating machinery.
  • The following adverse reactions have been reported, but were in most instances mild and temporary: transient blurring of vision, ocular discomfort or irritation, matting or stickiness of eyelashes, photophobia, hypersensitivity, eyelid edema, and hyperemia.

To report suspected adverse reactions, contact Bausch & Lomb Incorporated at 1-800-321-4576 or FDA at 1-800-FDA-1088 or FDA.gov/medwatch.

Click here for full Prescribing Information

Indications and Usage

LACRISERT® (hydroxypropyl cellulose ophthalmic insert) is indicated in patients with moderate to severe dry eye syndromes, including keratoconjunctivitis sicca. LACRISERT® is indicated especially in patients who remain symptomatic after an adequate trial of therapy with artificial tear solutions.

Important Safety Information

  • LACRISERT® (hydroxypropyl cellulose ophthalmic insert) is contraindicated in patients who are hypersensitive to hydroxypropyl cellulose.
  • Instructions for inserting and removing LACRISERT® should be carefully followed.

Important Safety Information

LACRISERT® (hydroxypropyl cellulose ophthalmic insert) is contraindicated in patients who are hypersensitive to hydroxypropyl cellulose.