The prevalence of dry eye disease (DED) continues to rise, with numbers reflecting approximately 38 million adults suffering from DED in the US. Given its strong association with advancing age, the burden of DED is expected to increase further as the population ages. Additionally, there has been a notable rise in DED among young adults and even children, linked, in part, to lifestyle factors such as screen time and cosmetic use.1,2
While only 18 million of those living with DED have received a formal diagnosis, even fewer are being actively treated. This highlights current deficiencies in both diagnosis and treatment. Managing this multifactorial condition is further complicated by patient compliance and treatment cost burden.1 Early assessment of the ocular surface and proactive management strategies can help address these challenges.
We spoke with Shane Kannar, OD; Kaleb Abbott, OD, MS, FAAO, FOWNS; Cecelia Koetting, OD, FAAO, Dipl. ABO; and Jeffry Gerson, OD, FAAO about their approach to diagnosing and treating this complex condition.
Dry eye disease overview
DED is a multifactorial disease of the ocular surface characterized by tear film instability, ocular surface inflammation, and neurosensory abnormalities. Patients commonly report symptoms such as dryness, burning, foreign body sensation, tearing, photophobia, fluctuating vision, itching, and redness. Tear film instability and resultant ocular surface damage can compromise corneal integrity, contributing to light scatter and visual fluctuation.3
The relationship between signs and symptoms in DED is not always straightforward. Some patients, particularly those with neurosensory abnormalities, may experience significant symptoms despite minimal clinical signs while others may demonstrate notable ocular surface findings with few symptoms. In addition, other ocular surface conditions may coexist with DED, making accurate diagnosis and a multimodal management approach essential.3
DED also significantly affects quality of life (QoL), impacting visual function, daily activities, workplace productivity, mental health, and overall well-being, while contributing to substantial economic burden.1
Ocular surface assessment: Establishing the diagnosis
Some DED tests rely on subjective scoring, and the sequence of testing can influence outcomes. Since DED is a dynamic condition, symptoms can vary over time, and test results may be affected by environmental factors, time of day, and recent lubricating drop instillation.3
When determining DED diagnosis, it’s important to undergo a systematic ocular surface evaluation. The Tear Film & Ocular Surface Society (TFOS) Dry Eye Workshop (DEWS) III Diagnostic Methodology paper is recommended as a guide to dry eye evaluation and diagnosis.3
Patient history and risk factors
Patient history is essential. Understanding a patient's systemic diseases, medications, digital device usage, contact lens history, and environmental factors can help pinpoint the underlying cause of DED.3
Several risk factors are associated with DED. Among the most well-established are age and sex, with older adults and female patients at higher risk. However, these are not the only contributors. Autoimmune disorders, gut dysbiosis, hormonal imbalance, dermatologic disease, chronic pain conditions, and mental health disorders have also been implicated in the development and severity of DED.4
Ocular conditions, including allergic conjunctivitis and blepharitis, as well as a history of ocular surgery, particularly refractive and cataract procedures, are well-established risk factors for DED.10 Meibomian gland dysfunction (MGD) is the most common cause of evaporative dry eye, with clinic-based studies estimating that over 80% of DED patients have concurrent MGD.11
Additional modifiable risk factors include prolonged digital device use, which reduces blink rate and promotes tear film instability; use of eye cosmetics, particularly eyeliner applied along the lid margin, which can obstruct meibomian gland function; and environmental exposures such as low humidity, high wind speed, air pollution, and temperature extremes.12-14
Validated questionnaires
Validated questionnaires can be useful for initiating patient discussions, monitoring symptom severity over time, and standardizing assessment in clinical practice. A variety of validated instruments are available, which can make selection challenging; however, commonly used tools include the original Ocular Surface Disease Index (OSDI), the OSDI-6, the Standard Patient Evaluation of Eye Dryness (SPEED), and the Dry Eye-Related Quality-of-Life Score (DEQS).
According to the TFOS DEWS III Diagnostic Methodology, the OSDI-6 is currently recommended as a screening questionnaire, with a cutoff score >4 suggesting dry eye disease, due to its reduced respondent burden with only six items (Figure 1).3
Figure 1: Example of the OSDI-6 Questionnaire.
Slit lamp exam
A comprehensive slit lamp examination of the anterior segment is essential in the evaluation of DED and OSD. The examination should be systematic, with attention to signs of tear film instability, eyelid disease, and ocular surface damage.3
Eyelashes and lid margins:
Telangiectasia, erythema, rosacea, anterior and posterior blepharitis, trichiasis, distichiasis, madarosis, collarettes/cylindrical dandruff, and abnormalities of the meibomian gland orifices (e.g., obstruction, pouting, capping, or dropout). Meibomian gland expression may reveal reduced expressibility or altered meibum quality, consistent with meibomian gland dysfunction.
Eyelids and blink function:
Assessment of lid position and function including ectropion, entropion, lagophthalmos, incomplete blink, dermatochalasis, and floppy eyelid syndrome. Lid wiper epitheliopathy may be identified with lissamine green staining and is often associated with increased frictional stress at the ocular surface.
Palpebral conjunctiva:
Follicles, papillae, hyperemia, edema, and scarring. Conjunctival inflammation and mechanical changes may contribute to tear film instability and ocular surface irritation.
Bulbar conjunctiva:
Hyperemia, chemosis, conjunctivochalasis, pinguecula, and pterygium. Lissamine green staining may demonstrate interpalpebral or exposure-related staining patterns consistent with ocular surface compromise.
Tear film:
Tear meniscus height, tear debris, and mucus strands. Fluorescein tear break-up time (TBUT) is used to assess tear film stability and is typically reduced in evaporative and mixed forms of DED.3
Cornea:
Fluorescein staining patterns including punctate epithelial erosions, epithelial basement membrane dystrophy (EBMD), Salzmann nodular degeneration, filaments, marginal keratitis, infectious or sterile ulceration, and corneal scarring (including post-operative changes).
Overall, slit lamp findings should be interpreted in the context of ocular surface homeostasis, recognizing that evaporative and aqueous-deficient mechanisms frequently coexist in DED.3
Diagnostic tests for dry eye disease
Diagnostic testing in DED includes objective measures of tear film homeostasis, ocular surface structure, and inflammation. Commonly used tests include meibography, tear osmolarity, corneal sensitivity assessment, Schirmer testing, and inflammatory markers such as matrix metalloproteinase-9 (MMP-9).3
- Tear osmolarity: Tear osmolarity reflects tear film homeostasis and is considered a key diagnostic biomarker in DED. Values >308 mOsm/L or an inter-eye difference >8 mOsm/L are suggestive of tear film instability consistent with dry eye disease.3
- MMP-9 testing: MMP-9 is an inflammatory biomarker elevated in the tears of patients with ocular surface inflammation. Point-of-care testing can aid in identifying inflammatory contributions to DED and may help guide anti-inflammatory treatment strategies.3
Personalizing treatment for multifactorial disease
As already discussed, DED is a multifactorial condition driven by overlapping mechanisms. Because of this complexity, treatment must be individualized based on each patient’s dominant disease drivers, severity, and response to therapy.
The TFOS DEWS III framework emphasizes identifying and treating the underlying drivers of tear film instability, including abnormalities of the lipid, aqueous, and mucin/glycocalyx components of the tear film, as well as inflammation and neurosensory abnormalities—rather than relying on a rigid stepwise escalation model.3
Treatments are often used concurrently and adjusted dynamically rather than escalated in a linear sequence. Management should therefore be guided by ongoing reassessment. Therapy is modified based on persistent symptoms, tear film instability, progression of ocular surface damage, or increasing inflammation.
Within this framework, treatment selection is not strictly tied to disease severity, as therapeutic options, including lubricating drops, prescription therapies, in-office procedures, biologics, and amniotic membrane or autologous serum, may be appropriate at any stage of disease.
Instead, management is individualized based on the patient’s dominant pathophysiology, symptom burden, clinical findings, treatment response, and practical factors such as access, cost, and adherence. The goal is targeted, mechanism-based therapy rather than escalation by severity alone.
First-line OTC strategies as foundational therapy
Lifestyle modifications and OTC therapies remain important cornerstones of DED management and are frequently used throughout the disease course, either alone or in combination with prescription and procedural treatments. Recommendations should be tailored to the patient's underlying disease mechanisms, symptom burden, and preferences.
Attention should be given to sleep quality, digital device habits, cosmetic practices, environmental exposures, and systemic medications that may contribute to ocular surface disease.
Common OTC strategies include the following:7
- Tear supplements: Lubricating drops are designed to supplement and stabilize the tear film by mimicking deficient tear components. Formulations vary considerably and although effective for symptom relief, they do not replicate the full biologic complexity of natural tears.
- Lid hygiene: Cleansers, sprays, foams, wipes, and gels can help reduce debris, bacterial overgrowth, biofilm, Demodex and inflammatory load along the lid margin.
- Available formulations may include ingredients such as hypochlorous acid, hyaluronic acid, tea tree oil, okra-derived extracts, manuka honey, or surfactants, depending on the underlying condition being addressed.
- Warm compresses: Warm compress therapy, with a microwaveable, electronic or air activated mask, is commonly recommended for MGD to soften and liquefy altered meibum, facilitating gland expression and improving lipid layer function. Compress therapy is typically followed by gentle lid massage to promote evacuation of stagnant gland contents.
- Nutraceuticals: Nutritional supplementation may provide benefit in select patients with DED, particularly those with MGD. Re-esterified Omega-3 fatty acids containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been associated with improvements in dry eye signs and symptoms in some studies, although findings have been mixed across clinical trials.7
- Gamma-linolenic acid (GLA), an omega-6 fatty acid, in combination with Omega-3 PUFAs, has also demonstrated benefit through its anti-inflammatory effects and may improve ocular comfort and tear function.16
- Emerging evidence suggests that omega-7 fatty acids, particularly palmitoleic acid from sea buckthorn oil, may improve symptoms and tear film parameters by supporting mucosal surface health and reducing ocular surface inflammation, although larger studies are needed to better define their role in DED management.15
- Additionally, combinations containing lutein, zeaxanthin, curcuminoids, and vitamin D have shown promise in improving tear parameters and reducing ocular surface inflammatory markers such as MMP-9.7
Prescription treatment options for dry eye disease
Anti-inflammatory agents
Prescription anti-inflammatory therapies are considered when there is evidence of ocular surface inflammation, persistent symptoms despite baseline therapy, or when the underlying disease mechanism warrants earlier intervention. These treatments may be used at any stage of DED depending on clinical presentation.
Corticosteroids
Topical corticosteroids are used for short-term control of ocular surface inflammation, particularly during flares, significant staining, or as a bridge when initiating longer-term immunomodulatory therapy. They provide rapid symptom relief but require monitoring due to potential adverse effects with prolonged use.7
Immunomodulators
These agents target chronic inflammatory pathways in DED and are typically used for longer-term disease control. Cyclosporine reduces T-cell activation and inflammatory cytokine production, supporting tear film restoration in chronic inflammatory and aqueous-deficient dry eye disease. While multiple concentrations and formulations are available, differences in drug delivery vehicles and emulsions may influence tolerability and clinical response, and individual patients may respond better to one formulation than another.
Lifitegrast blocks LFA-1/ICAM-1 interaction, reducing T-cell adhesion and downstream inflammatory signaling, and is used in symptomatic inflammatory DED.
Anti-evaporative
Perfluorohexyloctane is a non-aqueous, semifluorinated alkane used to reduce tear film evaporation in evaporative dry eye disease. It works by spreading across the tear film lipid layer, stabilizing the air–tear interface and reducing evaporative loss without relying on traditional surfactants or preservatives.
It is primarily used in patients with meibomian gland dysfunction–driven evaporative DED, particularly when tear film instability is a dominant feature.
Neuromodulator
Varenicline solution is an intranasal spray that activates the trigeminal parasympathetic pathway and lacrimal functional unit (LFU) via nasal mucosal receptors, stimulating the nasolacrimal reflex and increasing natural tear production. It is used in aqueous-deficient or mixed dry eye disease where tear volume is a limiting factor.
Acoltremon ophthalmic solution is a TRPM8 agonist that activates the LFU by stimulating corneal cold-sensitive sensory nerves, increasing basal tear production via TRPM8 receptor activation. It is used in aqueous-deficient or mixed dry eye disease where tear volume deficiency contributes to disease burden.
Topical biologics
Topical biologic therapies are used to support ocular surface function and healing by delivering growth factors, cytokines, and bioactive proteins that more closely approximate the natural tear film environment than conventional artificial tears.7 These agents are particularly useful in not only patients with severe ocular surface damage and corneal neurologic dysfunction, but those with early or mild DED as well.
Autologous serum tears (ASED) and platelet-rich plasma (PRP) are derived from the patient’s own blood and contain a complex mixture of growth factors, vitamins, immunoglobulins, and neuromediators that support epithelial health.7 These therapies promote epithelial cell proliferation, reduce apoptosis, and enhance ocular surface regeneration in mild to severe DED and corneal neurological dysfunction-related disease states.
Another biologic therapy used in ocular surface disease is cenegermin, a recombinant human nerve growth factor indicated for neurotrophic keratitis. It promotes corneal nerve regeneration and epithelial healing by supporting neuronal survival and restoring corneal sensitivity. While not a traditional dry eye therapy, it is relevant in cases where severe ocular surface disease overlaps with neurotrophic dysfunction and impaired corneal healing capacity.
Minimally invasive treatments
Minimally invasive in-office and device-based procedures are an important component of DED management and are used in conjunction with topical, systemic, and regenerative therapies. These interventions target tear retention, MGD, ocular surface inflammation, and epithelial compromise and may be utilized across disease severities depending on clinical findings, response to therapy, and access considerations such as insurance coverage and cost.
Minimally invasive interventions clinicians can consider for DED include:
- Punctal occlusion: Reduces tear drainage by partially or completely blocking the puncta, increasing tear retention on the ocular surface. Traditional silicone or collagen plugs are commonly used in aqueous-deficient and mixed DED when inflammation is controlled.
- Cross-linked hyaluronic acid hydrogel plugs offer a resorbable alternative that also delivers sustained hydration via water-binding properties, providing both mechanical occlusion and a lubricating, tear-stabilizing effect.
- Amniotic membrane therapy: Provides a biologically active scaffold rich in growth factors, anti-inflammatory mediators, and extracellular matrix components that support epithelial healing. Although more commonly associated with advanced ocular surface disease, persistent epithelial defects, and neurotrophic or inflammatory compromise, they may be utilized across all stages of dry eye disease when clinically indicated.
- Ocular surface lavage: Conjunctival fornix irrigation is used to mechanically remove inflammatory debris, allergens, biofilm, and toxic tear film components that may contribute to ocular surface irritation and inflammation. It can be particularly helpful in patients with significant lid margin disease, exposure to environmental irritants, or refractory surface inflammation.
- Thermal pulsation therapy: Applies controlled heat and pressure to the eyelids to liquefy meibum and facilitate expression from obstructed meibomian glands. It improves gland function and supports tear film lipid layer stability and is primarily used in evaporative DED associated with MGD.
- Light-based therapies: Intense pulsed light (IPL) is used in rosacea-associated and MGD-related dry eye disease to reduce periocular inflammation, abnormal telangiectatic vessels, microbial load, and oxidative stress, while improving meibomian gland function and tear film stability.
- Photobiomodulation (low-level light therapy), though less extensively studied in use for DED/OSD, uses specific wavelengths of light to modulate cellular activity, reduce inflammation, and support tear film homeostasis.
- Lid margin debridement: Mechanically removes keratinized debris, biofilm, and obstructive material from the lid margin, improving meibomian gland orifice patency and enhancing meibum flow into the tear film. While it can be done standalone, it is often utilized in conjunction with light based therapies and thermal pulsation.
- Specialty contact lenses: Therapeutic contact lenses provide mechanical protection and a hydrated environment for the ocular surface. Bandage lenses can be used short term to support epithelial healing and reduce friction, while scleral lenses vault the cornea and maintain a fluid reservoir that improves vision, comfort, and can be used as a more long term therapy for ocular surface stability in DED.
Improving patient adherence to treatment plan and real-world outcomes
Adherence presents a significant challenge to effective treatment. When patients do not adhere, it can lead to worse disease outcomes and a greater burden for both patients and healthcare providers.8 A study involving patients with DED found that 89.8% did not use eye drops at the recommended frequency, and 81.7% were unsure of the suggested schedule.9
Common reasons for non-adherence include poor tolerability, blurred vision, insufficient or delayed symptom relief, high dosing frequency, and limited access to eye drops, including physical access to pharmacies or medications and financial barriers such as insurance coverage and copay costs.9
With this in mind, patient education and expectation setting are essential to improving adherence. Simplifying treatment regimens, clearly explaining the rationale for each recommendation, and ensuring appropriate follow-up and monitoring can all support more consistent use of therapy.
However, cost and access remain significant barriers, as even over-the-counter and prescription options can create financial burden for patients. Clinicians should be aware of available cost-saving programs, manufacturer assistance initiatives, and pharmacy cash-pay arrangements that may help reduce out-of-pocket expense and improve treatment continuity.
Overall, OTC and prescription therapies should be selected based on patient-specific needs, access, and sustainability rather than a rigid treatment sequence.
Key takeaways for clinical practice
DED is a multifactorial condition requiring an individualized, mechanism-based approach rather than a uniform treatment sequence. Early identification of underlying drivers and targeted intervention are essential to improving outcomes.
Management should integrate clinical findings, objective testing, and patient-specific factors, with ongoing reassessment to guide therapy modification over time due to variable sign–symptom correlation.
Optimal care often involves combining OTC, prescription, procedural, biologic, and regenerative therapies based on disease profile and patient access. Clinicians are central to setting expectations, supporting adherence, and addressing barriers to care to improve long-term outcomes and quality of life.
