Tailoring treatment to the patient: Prescription medications for dry eye disease

Dry eye disease (DED) is a common ocular condition marked by a loss of homeostasis anywhere in the cycle, causing or worsening tear film instability, hyperosmolarity, and inflammation of the ocular surface.¹ This condition significantly impairs visual quality, leading to challenges in daily activities such as driving, reading, and computer use.² Addressing DED is crucial for improving patient satisfaction and quality of life and maintaining practice efficiency.^3,4

Supportive care often falls short for patients with DED

Patients with DED frequently report symptoms including burning, stinging, grittiness, foreign body sensation, light sensitivity, ocular pain, and blurred vision.^2,5,6 These symptoms negatively impact quality of life and may also reduce visual function and productivity.^2,6 If left untreated, DED may lead to recurring patient complaints,⁷ persistent discomfort, and long-term ocular damage.⁵ Early diagnosis and intervention are essential to prevent these adverse outcomes and improve the patient’s visual function and overall well-being.⁵

DED can be identified through comprehensive evaluations, including clinical assessments like corneal staining⁸ and Schirmer tests.⁹ Management strategies often include artificial tear supplements, prescription therapies targeting various causative factors, and lifestyle modifications.¹⁰ Proactive management can alleviate symptoms, enhance visual function, and reduce risk of increased follow-ups.⁵

Prescription therapies for DED

DED is commonly categorized as aqueous deficient, evaporative, or mixed. Excessive tear evaporation due to meibomian gland dysfunction is the leading cause, affecting approximately 90% of patients with DED.^11,12

Prescription treatments target the insufficient tear production, inflammatory pathways, or excessive evaporation that perpetuate DED. Cyclosporine-based therapies (Restasis, AbbVie; Cequa, Sun Ophthalmics; Vevye, Harrow) act by inhibiting T-cell activation through the calcineurin-phosphate pathway, resulting in increased tear production and protection of conjunctival goblet cells.^13-15 Cequa employs nanomicellar technology to enhance cyclosporine delivery¹⁵ whereas Vevye uses a semifluorinated alkane (SFA), perfluorobutylpentane (PFBP or F4H5), as a vehicle.¹⁶

Lifitegrast ophthalmic solution 5% (Xiidra; Bausch+Lomb) addresses ocular inflammation through mechanisms such as inhibiting T-cell activation, blocking T-cell recruitment to the ocular surface, and reducing inflammatory cytokine secretion.^15,17 Lifitegrast binds to lymphocyte function-associated antigen-1, a protein found on the surface of leukocytes, preventing its interaction with its ligand intercellular adhesion molecule-1.^15,17

Perfluorohexyloctane ophthalmic solution (Miebo; Bausch+Lomb) targets the evaporative aspect of DED.^18,19 Composed entirely of perfluorohexyloctane (PFHO or F6H8), Miebo reduces tear evaporation by forming a stable monolayer on the tear film and has a prolonged ocular surface residence time due to its low volatility.¹⁸ In doing so, PFHO compensates for deficiencies in meibum and stabilizes the lipid layer of the tear film, which results in improved tear film homeostasis.¹⁸ Although both Miebo and Vevye contain an SFA (chemically inert molecules consisting of a fluorocarbon segment and a hydrocarbon segment),²⁰ their physiochemical properties lead to distinct functionalities. The SFA in Vevye’s formulation (PFBP) serves as a vehicle to solubilize cyclosporine better than PFHO yet does not inhibit evaporation.¹⁶ In contrast, Miebo (PFHO) exhibits antievaporative effects due to its unique chemical structure.¹⁸ The longer chain length of PFHO enables the formation of a stable monolayer at air-liquid interfaces.²¹ Additionally, PFHO’s higher boiling point²² (indicating lower volatility) ensures slower evaporation and prolonged ocular surface residence time.^18,23 Unlike PFBP, PFHO was shown to stabilize the tear film lipid layer in a 7-day study in rabbits.²⁴

Varenicline nasal spray (Tyrvaya; Viatris) stimulates tear production via the trigeminal parasympathetic pathway.²⁵ Varenicline, a nicotinic acetylcholine receptor agonist, activates this pathway when administered intranasally.²⁵

Symptom reduction as a key differentiator among treatments

Clinical trials evaluating cyclosporine-based treatments for DED include randomized, vehicle-controlled studies of Restasis,²⁶ Cequa,²⁷ and Vevye.^28,29 Across these studies, cyclosporine-based eye drops showed significantly greater improvements in DED signs (eg, corneal staining, Schirmer test) compared with vehicle controls.^26-29 However, reductions in DED symptoms were generally similar between the active treatment and control groups.^26-29 For Restasis, no significant differences were observed between the treatment and control groups for symptoms such as eye dryness, sandy/gritty sensation, burning, stinging, itching, and pain, although a notable improvement in blurred vision was observed.²⁶ For Cequa, changes in the global symptom score were comparable to the vehicle.²⁷ For Vevye, the primary symptom end points (Ocular Surface Disease Index score in ESSENCE-1 and eye dryness in ESSENCE-2) were not met, although secondary analyses showed a significantly greater reduction in eye dryness for Vevye compared with vehicle in ESSENCE-1.^28,29

Lifitegrast was assessed in 4 randomized, placebo-controlled trials (phase 2, OPUS-1, OPUS-2, OPUS-3).^30-33 Pooled results from these trials demonstrated that lifitegrast effectively addressed both prespecified end points: signs (corneal staining) and symptoms (eye dryness and discomfort) of DED, with improvements in eye dryness as early as 2 weeks after treatment initiation.^30-33

PFHO was found to deliver rapid and sustained improvements in both signs (corneal staining) and symptoms (eye dryness, burning/stinging) of DED, with consistently greater effects than a hypotonic saline (0.6%) control in 2 randomized controlled trials (GOBI, MOJAVE).^34,35 Both signs and symptoms were improved by the earliest assessment time point of day 14. A postmarketing study recently demonstrated relief of patients’ symptoms as early as day 3 of treatment.³⁶

In randomized, vehicle-controlled studies (ONSET-1, ONSET-2), varenicline nasal spray outperformed the vehicle in improving Schirmer test scores, consistent with its mechanism of action), and significantly reduced eye dryness at most assessments in ONSET-1.^37,38

Implications for clinical practice

Identifying and appropriately treating DED is vital to ensure patient comfort and visual quality and function. Treatment decisions should consider disease etiology, symptom burden, and patient preferences. For aqueous-deficient DED, cyclosporine-based products or varenicline nasal spray may be appropriate, with patient choice guiding between a drop or nasal spray. PFHO is particularly effective for evaporative DED, whereas lifitegrast may be favored in cases involving inflammation. Products that alleviate symptoms, such as lifitegrast and PFHO, may be preferable for patients most troubled by discomfort. A personalized approach to therapy selection can optimize outcomes for individuals with DED.

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