Artificial Tears Demystified: A Clinical Guide to Choosing the Right Formulation for Your Dry Eye Patients

Dry eye disease (DED) remains one of the most prevalent and challenging conditions encountered in optometric practice. With a market saturated with dozens of artificial tear formulations—each claiming superior efficacy—eye care practitioners are often left asking: Which drop is best for this particular patient?

A recent systematic review by Semp et al. (2023) sought to address this clinical conundrum by analysing 64 randomized controlled trials (RCTs) comparing different artificial tear formulations. Their findings offer valuable, evidence-backed insights to guide prescribing behaviour and refine treatment protocols.

This blog post synthesises their key findings and presents a practical guide for matching artificial tear formulations to specific clinical presentations.

The Role of Artificial Tears in Dry Eye Management

Artificial tears are more than just symptomatic relief. According to the review, they play multiple therapeutic roles:

Hydration and lubrication

Restoration of tear film osmolarity

Support of ocular surface healing

Adjunctive use in contact lens wear, conjunctivitis, and minor abrasions

Their low risk profile and ease of use make them the mainstay of first-line treatment for mild to moderate DED. However, one formulation does not fit all.

Key Insights from the Systematic Review

Combination drops outperform single-ingredient formulations.

PEG-containing formulations are more effective than CMC or HPMC-based drops.

Lipid-based or cationic emulsions work better for evaporative dry eye.

Trehalose, CoQ10, and osmoprotectants enhance anti-inflammatory and cytoprotective effects.

Preservative-free drops are preferable—especially in moderate to severe DED.

Symptomatic relief usually occurs within 1 month, but signs take longer (≥3 months) to improve.

Formulation Matching: What to Prescribe and When

🟢 Aqueous Deficient Dry Eye

Key Features:

Reduced Schirmer’s test score

Tear film breakup time (TBUT) may still be within normal range

Lissamine Green or Rose Bengal staining in interpalpebral zone

Recommended Formulations:

Sodium hyaluronate or hyaluronic acid (HA): High water-binding capacity, excellent retention time.

High molecular weight HA provides better symptom relief and anti-inflammatory benefits than low MW forms.

Combination drops (e.g., HA + CMC or HA + trehalose): Enhanced performance via dual action—hydration + antioxidation.

PEG-based lubricants: Longer ocular surface retention.

Clinical Tip: If no improvement in symptoms after 4 weeks of compliant use, reassess the diagnosis or consider advanced therapies like punctal plugs or anti-inflammatory agents.

🟡 Evaporative Dry Eye (Meibomian Gland Dysfunction)

Key Features:

Normal tear volume but fast TBUT (<5 seconds)

Increased lipid layer thinning on interferometry

Often associated with rosacea, blepharitis

Recommended Formulations:

Lipid-based emulsions or sprays (e.g., Systane Balance, Tears Again): Mimic natural meibum and improve lipid layer stability.

Cationic emulsions (e.g., Cationorm): Enhance lipid spreading and retention on the ocular surface.

Omega-3 or phospholipid-based formulations: Effective for patients with significant lipid deficiency.

Evidence: Liposomal sprays showed superior improvement in TBUT and symptoms in those with poor baseline lipid layer grading (Craig et al., 2021).

🔵 Mixed Mechanism DED

Key Features:

Both aqueous and evaporative signs

Abnormal TBUT and low Schirmer’s

Diffuse staining

Recommended Formulations:

Multifunctional combinations (e.g., Systane Complete, Refresh Optive Fusion): Target multiple tear film layers—aqueous, mucin, and lipid.

HA + trehalose + CoQ10: Combats oxidative stress and supports epithelial repair.

Clinical Tip: Consider these in patients with moderate-to-severe symptoms or ocular surface damage.

🔴 Hyperosmolar Dry Eye

Key Features:

Tear film osmolarity >308 mOsm/L

Burning sensation, foreign body sensation

Poor correlation with Schirmer’s or TBUT

Recommended Formulations:

Osmoprotectant-based drops (e.g., erythritol, levocarnitine, trehalose): Counteract the cellular stress induced by hyperosmolarity.

Low-osmolarity HA drops (e.g., 150 mOsm): Proven to reduce corneal staining and discomfort (Troiano et al., 2008).

Note: Baseline osmolarity testing, where available, can guide formulation selection.

🟠 Contact Lens Wearers

Considerations:

Must be compatible with lens material

Should not cause blurring or deposits

Preferably preservative-free

Recommended Formulations:

Low viscosity HA or PEG-based drops (e.g., Blink Contacts, Refresh Contacts): Provide relief without interfering with lens clarity.

Preservative-free unit-dose options: Reduce risk of hypersensitivity or biofilm formation.

Tip: Recommend application before lens insertion and after removal—not while lenses are worn unless explicitly approved.

⚪ Post-Surgical or Inflamed Ocular Surface

Features:

Recent LASIK, cataract surgery, or corneal insult

Higher inflammation risk

Delayed epithelial healing

Recommended Formulations:

HA + CoQ10 or tamarind seed polysaccharide: Promote epithelial regeneration.

Non-preserved formulations: Minimise cytotoxicity.

HA + trehalose: Effective against oxidative and UV-induced damage.

Evidence: CoQ10 + HA reduced epithelial hyperreflectivity and improved comfort post-surgery (Postorino et al., 2018).

Preservatives: Handle with Caution

Avoid:

Benzalkonium chloride (BAK): Toxic to epithelial cells; exacerbates DED.

Prefer:

Polyquaternium (Polyquad)

Sodium perborate or purite (vanishing preservatives)

Preservative-free unit doses in moderate to severe DED or frequent use.

Additional Considerations in Choosing a Drop

Patient Dexterity: Liposomal sprays are easier for elderly or tremor patients.

Lifestyle: Preservative-free multi-dose bottles offer convenience and hygiene.

Price Sensitivity: Guide toward effective but affordable options, avoiding trial-and-error wastage.

Compliance: Most studies assume 4x/day dosing—actual adherence is often lower. Educate and follow up.

When to Re-Evaluate

Artificial tears aren’t a panacea. If there is no symptomatic improvement within 4 weeks, despite regular use:

Reassess for:

Undiagnosed MGD

Neurotrophic keratitis

Sjögren’s syndrome

Allergic conjunctivitis

Consider:

Switching to anti-inflammatories (e.g., cyclosporine)

In-office procedures (e.g., LipiFlow)

Specialist referral

Conclusion: A Personalized, Evidence-Based Approach

This systematic review reinforces that artificial tears are effective—but only when matched to the right clinical profile. As optometrists, we need to move beyond the “one-size-fits-all” mentality and use our clinical tools—history taking, validated questionnaires, TBUT, osmolarity, and meibography—to identify the underlying dry eye subtype.

Armed with this knowledge, we can make informed, tailored prescribing decisions that not only relieve symptoms but also protect and restore the ocular surface.

References

Semp DA, Beeson D, Sheppard AL, Dutta D, Wolffsohn JS. Artificial Tears: A Systematic Review. Clinical Optometry. 2023;15:9-27. doi:10.2147/OPTO.S350185

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