The Evolving Landscape of Dry Eye Disease Risk Factors: A Comparative Analysis of the TFOS DEWS II (2017) and DEWS III (2025) Reports

Abstract

Objective

To systematically compare the classification of risk factors for dry eye disease (DED) between the Tear Film and Ocular Surface Society (TFOS) International Dry Eye Workshop (DEWS) II (2017) and DEWS III (2025) reports, highlighting changes in the level of evidence certainty, modifiability status, and clinical implications.

Methods

The TFOS DEWS II Epidemiology Report and the TFOS DEWS III reports were analyzed. Risk-factor classifications were extracted and compared along two axes: evidence certainty (consistent, probable, inconclusive) and modifiability (non-modifiable, modifiable). Key changes were identified, grouped into categories that included upgrades, downgrades, and reclassifications, and then reorganized and transformed into a practical table format based on the level of evidence certainty.

Results

The DEWS II framework classified risk factors into a 2×3 matrix, whereas DEWS III introduced a more detailed 4-quadrant risk-factor matrix. This study effectively reorganized and transformed the aforementioned risk-factor matrix into a practical table format designed to maximize its clinical utility. The most notable change was the reclassification of meibomian gland dysfunction (MGD) from a non-modifiable to a modifiable risk factor, reflecting a shift toward early intervention and advances in treatment options. Other key updates included elevating thyroid disease, sarcoidosis, and anticholinergics from probable to consistent evidence, and downgrading hormone replacement therapy and air pollution from consistent to probable evidence. Several conditions, such as rosacea, pterygium, and psychiatric disorders, were reclassified from non-modifiable to modifiable. DEWS III also introduced revised diagnostic thresholds and a refined subtype classification system.

Conclusions

The shift from DEWS II to DEWS III marks a significant development reflecting an evolution in the understanding of DED risk factors. The reclassification of MGD as a modifiable risk factor has profound implications for clinical practice, emphasizing the importance of early detection and proactive management. By incorporating the updated criteria and providing this newly reorganized and transformed practical table, this framework can serve as a practical tool that facilitates the application of the consensus framework for researchers and clinicians, with the goal of improving clinical diagnostic precision and enhancing personalized patient care. These changes underscore the need for revised and updated clinical guidelines and support the identification of future research priorities.

Plain Language Summary

What is already known on this topic

The TFOS DEWS II (2017) and TFOS DEWS III (2025) reports provide the international consensus on dry eye disease risk factors, classifying them by the level of evidence certainty and modifiability. DEWS II organized risk factors into a 2×3 matrix, while DEWS III introduced a 4-quadrant risk-factor matrix with updated diagnostic thresholds and a refined subtype classification system.

What this study adds

This study offers the first systematic, side-by-side comparison of risk-factor classifications in DEWS II and DEWS III. It highlights key changes, including the reclassification of MGD from non-modifiable to modifiable, characterized as a paradigm shift. This study has reorganized and transformed the aforementioned risk-factor matrix into a practical table format, organized by level of evidence certainty, to facilitate the application of the framework for researchers and clinicians and to improve clinical diagnostic precision. Specifically, it tracks how the evidence base has evolved to elevate major systemic conditions, including thyroid disease and sarcoidosis, as well as medications such as anticholinergics, to the status of consistent risk factors. It also outlines the transition to the new three-category etiological subtype classification framework, which replaces the previous binary aqueous-deficient/evaporative model, and supports more targeted, mechanism-based management strategies by enabling clinicians to address etiological drivers in a personalized manner.

How this study might influence research, practice, or policy

The findings support the need for early detection of MGD and updating clinical guidelines. A clear overview of modifiable and non-modifiable risk factors by level of evidence certainty is provided. Research priorities could include longitudinal MGD studies, intervention trials for subclinical disease, and population-based studies in underserved areas.

Introduction

The Tear Film and Ocular Surface Society (TFOS) International Dry Eye Workshop (DEWS) reports represent the international consensus on the definition, classification, diagnosis, and management of dry eye disease (DED). The initial 2007 DEWS report established a foundational framework, which the 2017 TFOS DEWS II report greatly expanded.¹ Among its many contributions, the DEWS II Epidemiology Report offered a comprehensive classification of DED risk factors, categorizing them by evidence certainty (consistent, probable, or inconclusive) and modifiability (non-modifiable or modifiable).² DED affects hundreds of millions worldwide and is the leading cause of eye care visits, significantly impairing quality of life.^2,3 Recognizing DED risk factors is essential for identifying at-risk populations, developing preventive strategies, improving patient counseling, and guiding research priorities.^2,4 A structured classification of risk factors provides clinicians with a framework for holistic patient assessment and offers researchers a roadmap to investigate disease mechanisms. Meibomian gland dysfunction (MGD) has become the most common cause of DED, making its classification especially important.²

In 2025, TFOS published the DEWS III reports, updating and refining this framework after a decade of additional epidemiological and clinical research.³ The recent DEWS III report introduced a novel 4-quadrant risk-factor matrix, reorganized existing categories, incorporated newly identified risk factors, updated diagnostic thresholds, and refined the subtype classification system. The 2017 DEWS II report established a baseline, and the 2025 DEWS III report updated the risk factors, but it does not provide a historical comparison or cross-reconciliation of changes relative to the previous framework. However, no systematic comparison of how the risk-factor landscape has changed from DEWS II to DEWS III has been published to date. A targeted literature search conducted in April 2026 and updated in June 2026 confirmed the absence of any prior published systematic comparison of risk-factor classifications between DEWS II and DEWS III. This comparative study provides a novel, systematic, side-by-side, structured comparison of the risk-factor classifications in DEWS II and DEWS III. By highlighting significant changes, including upgrades, downgrades, and reclassifications, this study equips clinicians and researchers with a clear understanding of how the evidence base has evolved and discusses the clinical and research implications of these updates.

Methods

The comparative analysis in this study is based on two primary source documents: the TFOS DEWS II Epidemiology Report (Stapleton et al, 2017),² and the TFOS DEWS III reports, including the Executive Summary, Diagnostic Methodology report, Digest, and Management and Therapy report (Wolffsohn et al, 2025; Stapleton et al, 2025; Perez et al, 2026).^3,5–7 Risk factors for DED were extracted from each report and categorized using the classification frameworks and systems presented in the reports: by two essential input variables of evidence certainty and modifiability in DEWS II, and by a quadrant matrix framework, applying input variables of evidence certainty and modifiability in DEWS III. For DEWS II, risk factors were classified by evidence certainty (consistent, probable, inconclusive) and modifiability (non-modifiable, modifiable). For DEWS III, risk factors were organized by the level of evidence certainty and modifiability within a 4-quadrant matrix based on the illustration in Figure 5 of the Executive Summary of the DEWS III report,⁶ with additional attention to the refined subtype classification system. Because the two reports used different organizational frameworks, a 2×3 matrix (DEWS II) vs a 4-quadrant matrix (DEWS III), there were no overlapping categories to reconcile or disagreements to resolve before the comparison was conducted. The comparison was therefore performed by directly contrasting the risk-factor classifications between the two reports, with the aim of identifying changes in the certainty and modifiability of evidence between DEWS II and DEWS III. The detected changes constituted the results, which were presented with each framework shown as originally structured, in a systematic side-by-side manner.

Key changes were identified through a direct comparison of the two frameworks. The identified changes were categorized into four groups. These categories were defined using predefined criteria: upgraded was defined as an increase in the certainty of the evidence; downgraded was defined as a decrease in the certainty of the evidence; reclassified was defined as a change in modifiability status; and newly identified was defined as risk factors present only in DEWS III. These categories are outlined below:

• 1)Upgraded: Evidence certainty has increased (eg, from probable to consistent).
• 2)Downgraded: Evidence certainty has decreased (eg, from consistent to probable).
• 3)Reclassified: Modifiability status has been updated (eg, from non-modifiable to modifiable).
• 4)Newly identified: Present only in DEWS III.

The findings are presented in tabular form to enhance visual communication and enable direct comparison. Table 1 outlines the DEWS II risk-factor classification, while Table 2 presents the comprehensive DEWS III risk-factor matrix, reorganized and transformed from a 4-quadrant matrix layout into a practical table format based on the level of evidence certainty. Table 3 summarizes key findings and highlights the main differences between the two frameworks.

Table 1.

DEWS II Risk-Factor Classification (2017)

Category	Consistent Evidence	Probable Evidence	Inconclusive Evidence
Non-modifiable	• Age • Female sex • Asian ethnicity • MGD • Connective tissue diseases • Sjögren syndrome	• Diabetes • Thyroid disease • Rosacea • Pterygium • Psychiatric conditions	• Hispanic ethnicity • Menopause • Acne • Sarcoidosis
Modifiable	• Androgen deficiency • Digital screen use • Contact lens wear • Hormone replacement therapy • Environmental factors (pollution, low humidity) • Medications (antihistamines, antidepressants, anxiolytics, isotretinoin)	• Anticholinergics • Diuretics • Beta-blockers	• Oral contraceptives

Notes: Adapted from Stapleton et al, TFOS DEWS II Epidemiology Report (2017)².

Table 2.

Comprehensive DEWS III Risk-Factor Matrix (2025)

Order (Clock Position)	Quadrant	Evidence Certainty	Modifiability	Pathophysiological Domain	Specific Risk Factors
1 (9–12)	II	Consistent	Non-modifiable	Demographic factors	• Aging • Female sex and gender • Asian/non-white race
				Systemic disorders; Autoimmune disorders	• Sjögren’s disease • Rheumatoid arthritis • Systemic sclerosis • Systemic lupus erythematosus • Sarcoidosis • Thyroid disease • Inflammatory bowel disease • Psoriasis
				Systemic disorders; Hormonal disorders	• Diabetes
				Systemic disorders; Dermatological/atopic disease	• Asthma
				Systemic disorders; Pain Disorders	• Irritable bowel syndrome • Fibromyalgia • Chronic pelvic pain • Migraine • Other headache disorders • Osteoarthritis
				Ocular Disorders	• Facial nerve paralysis
				Surgery/Procedures	• Refractive surgery • Cataract surgery • Intravitreal injections • Eyelid and periorbital surgery • Periocular botulinum toxin injections • Hematopoietic stem cell transplantation
2 (6–9)	III	Consistent	Modifiable	Ocular Disorders Systemic disorders	• Meibomian gland dysfunction (MGD) • Anterior blepharitis • Allergic conjunctivitis • Ocular surface inflammatory or lid/tear conditions; Pterygium, Conjunctivochalasis • Thyroid eye disease • Ocular rosacea • Glaucoma • Hormone disorders: androgen deficiency • Dermatological/atopic disease: rosacea, eczema, allergy • Sleep disorders: sleepapnea, insomnia • Psychiatric disorders: depression,anxiety, stress • Other: Osteoporosis, Parkinson´s disease
				Medications	• Anti-cholinergics • Chemotherapeutics • Preserved topical medications • A derivatives (isotretinoin) • Dupilumab • Anti-androgen therapies
				Environment/Lifestyle	• Low humidity • Screen use • Contact lens wear • Use of cosmetics and skin care products
				Other/Nutritional	• Vitamin A deficiency • Vitamin C deficiency • Omega-3 fatty acid deficiency
3 (12–3)	I	Probable	Non-modifiable		• Dermatological/ atopic disease: Acne
				Systemic disorders	• Pain disorders: Temporomandibular joint disorder • Neurodevelopmental disorders: Autism
				Surgery or Procedures	• Cosmetic periocular and ocular procedures
				Other	• Genetic predisposition
4 (3–6)	IV	Probable	Modifiable		• Hormone disorders: Polycystic ovary syndrome
				Systemic disorders	• Dermatological/atopic disease: Acne
					• Psychiatric disorders/burnout
					• Other:Sinusitis
				Medications	• Estrogen replacement therapy • Proton pump inhibitors
				Environment/Lifestyle	• Air pollution (NO2, CO) • Temperature extremes (high or low temperatures) • Air conditioning or windy conditions
				Other/Nutritional	• Vitamin B12 deficiency • Vitamin D deficiency • Altered gut microbiome • Diet

Notes: Adapted from TFOS DEWS III reports (2025).^3,5–7 The quadrants’ designations follow standard mathematical mapping corresponding to designated clock positions (first column) to facilitate visual orientation (see The TFOS DEWS III Risk-Factor Framework (2025) for details). The vertical order in the table prioritizes the strength of evidence (with consistent factors first, from the top) rather than a clockwise arrangement.

Table 3.

Key Changes from DEWS II to DEWS III

Risk Factor	DEWS II Classification	DEWS III Classification	Type of Change
MGD	Non-modifiable, Consistent	Modifiable, Consistent	Reclassified (Paradigm shift)
Thyroid disease	Non-modifiable, Probable	Non-modifiable, Consistent	Upgraded
Sarcoidosis	Non-modifiable, Inconclusive	Non-modifiable, Consistent	Upgraded
Acne	Non-modifiable, Inconclusive	Non-modifiable, Probable	Upgraded
Anticholinergics	Modifiable, Probable	Modifiable, Consistent	Upgraded
Oral contraceptives	Modifiable, Inconclusive	Modifiable, Probable	Upgraded
Rosacea	Non-modifiable, Probable	Modifiable, Consistent	Reclassified + Upgraded
Pterygium	Non-modifiable, Probable	Modifiable, Consistent	Reclassified + Upgraded
Psychiatric conditions	Non-modifiable, Probable	Modifiable, Probable	Reclassified
Hormone replacement therapy	Modifiable, Consistent	Modifiable, Probable	Downgraded
Air pollution	Modifiable, Consistent	Modifiable, Probable	Downgraded

Notes: This table highlights the most clinically significant changes; parenthetical text denotes a fundamental clinical shift in disease understanding/classification, while additional minor reclassifications are detailed in the comprehensive TFOS DEWS III matrix (Table 2).

Results

The TFOS DEWS II Risk-Factor Framework (2017)

The DEWS II Epidemiology Report organized DED risk factors into a 2×3 matrix based on the certainty of evidence and modifiability, as shown in Table 1. Non-modifiable risk factors supported by consistent evidence included age, female sex, Asian ethnicity, meibomian gland dysfunction (MGD), connective tissue diseases, and Sjögren syndrome. Probable non-modifiable factors comprised diabetes, thyroid disease, rosacea, pterygium, and psychiatric conditions, while inconclusive non-modifiable factors encompassed Hispanic ethnicity, menopause, acne, and sarcoidosis. Modifiable risk factors with consistent evidence included androgen deficiency, digital screen use, contact lens wear, hormone replacement therapy, environmental factors (pollution, low humidity, sick building syndrome), and medications such as antihistamines, antidepressants, anxiolytics, and isotretinoin. Probable modifiable factors consisted of anticholinergics, diuretics, and beta-blockers, while oral contraceptives were classified as inconclusive modifiable risk factors.² In addition, the DEWS II Epidemiology Report included a meta-analysis of prevalence data, which demonstrated that dry eye prevalence increases linearly with age, by 2.0–10.5% per decade, depending on the diagnostic criteria used, and that clinical signs of dry eye showed a greater increase with age than symptom-based diagnoses.²

The TFOS DEWS III Risk-Factor Framework (2025)

The TFOS DEWS III report introduced a more detailed 4-quadrant matrix that classified risk factors based on two main input variables, evidence certainty (consistent vs probable) and modifiability (non-modifiable vs modifiable). The DEWS III matrix follows a Cartesian quadrant layout, as described in Badian (2023, Figure 2),⁸ which outlines the Cartesian unit system with four quadrants. In the original figure, presented in the DEWS III Executive Summary, Figure 5,⁶ the matrix consists of four quadrants, utilizing a bivariate spatial arrangement; the vertical axis (ordinate) categorizes risk factors from non-modifiable superiorly at the apex to modifiable inferiorly at the base, while the horizontal axis (abscissa) plots scientific certainty, progressing from consistent evidence on the far left to probable evidence on the far right of the horizontal axis. This spatial arrangement results in four distinct quadrants, each representing a specific combination of evidence certainty and modifiability. To describe the sequential order and spatial layout of these quadrants, the Cartesian-based schematic sectioning approach that aligns with standard mathematical coordinate mapping was applied (Badian, 2023):⁸ Quadrant I corresponds to the 12–3 o’clock position, Quadrant II corresponds to the 9–12 o’clock position, Quadrant III corresponds to the 6–9 o’clock position, and Quadrant IV corresponds to the 3–6 o’clock position. Within this designated 4-quadrant layout, the specific quadrants and clock positions correspond to distinct levels of evidence certainty and modifiability: Quadrant I (12–3 o’clock) includes probable and non-modifiable factors; Quadrant II (9–12 o’clock) includes consistent and non-modifiable factors; Quadrant III (6–9 o’clock) contains consistent and modifiable factors; and Quadrant IV (3–6 o’clock) covers probable and modifiable factors.

To facilitate efficient orientation for clinicians, researchers, and readers navigating Table 2 relative to Figure 5 of the TFOS DEWS III Executive Summary,⁶ the aforementioned clock positions have been applied. Moreover, the order in Table 2 is optimized for evidence-based presentation, prioritizing the strength of evidence by placing consistent factors before probable factors, regardless of their respective allocated quadrants. Consequently, the vertical, top-to-bottom arrangement in Table 2, where the sequential order of quadrants is determined based on evidence-focused hierarchy to optimize clinical utility and highlight the strength of evidence by descending certainty (II → III → I → IV), is utilized rather than the spatial clockwise sequence in the original TFOS DEWS III Figure 5.

The framework also incorporated pathophysiological domains to group related factors, as shown in Table 2. This table retains the original quadrant structure (Quadrants I–IV) and arranges the factors in an evidence-based order (consistent factors first, then probable factors). In addition to the risk-factor matrix, the TFOS DEWS III Diagnostic Methodology report introduced updated diagnostic thresholds, including an OSDI-6 score of ≥4 for symptom screening; an osmolarity cut-off of ≥308 mOsm/L (or an interocular difference >8 mOsm/L); a non-invasive tear breakup time of less than 10 seconds (<10 s); and refined ocular surface staining criteria (corneal fluorescein staining >5 punctate spots; lissamine green conjunctival staining >9 punctate spots; and/or lissamine green lid margin staining ≥2 mm in length and ≥25% in width). When fluorescein is used, the tear film stability cutoff is reduced from 10 seconds to 5 seconds to account for its invasive nature and the volume effect of the instillation.⁵

Key Changes from TFOS DEWS II to DEWS III

MGD: The Paradigm Shift

The most significant change is the reclassification of Meibomian gland dysfunction (MGD) from a non-modifiable, consistent risk factor in DEWS II to a modifiable, consistent risk factor in DEWS III. This shift reflects advances in therapeutic options, greater recognition of the potential of early intervention, and a fundamental reconceptualization of MGD as an actionable target rather than an unavoidable, age-related degenerative process. The DEWS III Executive Summary highlights that most dry eye disease (DED) is now recognized as evaporative or hyperevaporative in nature, with MGD as the primary driver.⁶ This reclassification represents an evolution in understanding that positions MGD not merely as a comorbidity but as the key target for early intervention and disease management.

Upgraded Risk Factors

For several risk factors, the certainty of evidence has increased, as summarized in Table 3. The upgrades include thyroid disease, from probable to consistent; sarcoidosis, from inconclusive to consistent; acne, from inconclusive to probable; anticholinergics, from probable to consistent; and oral contraceptives, from inconclusive to probable.

Downgraded Risk Factors

Two risk factors were downgraded in evidence certainty: hormone replacement therapy and air pollution, both moving from consistent to probable evidence (Table 3).

Reclassified Risk Factors (Modifiability Changed)

Several conditions were reclassified from non-modifiable to modifiable, including rosacea, pterygium, and psychiatric conditions (Table 3). This shift recognizes that these conditions are treatable and that effective management can reduce the risk of DED.

Newly Identified Risk Factors in TFOS DEWS III

TFOS DEWS III has introduced several risk factors not explicitly listed in DEWS II, including dupilumab, antiandrogen therapies, chemotherapeutic agents, an altered gut microbiome, and specific nutritional deficiencies (vitamin B12 and D). The framework also broadened the range of autoimmune, pain, and surgical/procedural factors, as shown in Table 2.

New Subtype Classification in TFOS DEWS III

Beyond reclassifying individual risk factors, DEWS III introduced a fundamental shift in how the conceptualization of DED subtypes is understood. Specifically, this new framework moves beyond the traditional binary classification of aqueous-deficient and evaporative DED and categorizes DED into three broad etiological categories: tear-film component deficiencies, eyelid anomalies, and ocular-surface abnormalities.⁷ This refined three-category classification framework aims to support more targeted, mechanism-based treatment strategies, enabling clinicians to choose therapies that address the specific factors influencing each patient.

Discussion

This comparative analysis demonstrates that transitioning from TFOS DEWS II to DEWS III represents a substantial evolution in the understanding of DED risk factors, rather than a mere administrative update. These revisions reflect a decade of accumulated epidemiological and clinical evidence, advances in treatment options, and a deeper understanding of the complex, multifactorial nature of DED.

Clinical Implications of the MGD Reclassification

As highlighted in the introduction, the classification of MGD is particularly consequential. The reclassification of MGD as a modifiable risk factor has profound implications for clinical practice. In the DEWS II epoch (2017–2025), MGD was often viewed as an inevitable consequence of aging and demographic factors, with management focused on symptomatic relief. The DEWS III framework positions MGD as an actionable target, emphasizing early detection, proactive intervention, and the potential to alter the disease trajectory.⁹ This shift aligns with a broader movement in medicine toward preventive and precision-based approaches, impacting patient counseling, clinical guidelines, and healthcare policy. Clinicians should now routinely assess meibomian gland function even in asymptomatic individuals. This is especially important in the older age strata of the population, where subclinical MGD is highly prevalent.¹⁰ The high prevalence of asymptomatic MGD documented in recent large clinic-based and population-based studies underscores the significance of the active early screening approach.^11–13

Understanding Upgrades and Downgrades

The upgrade of thyroid disease, sarcoidosis, and anticholinergics to consistent evidence reflects the maturation of the evidence base linking these factors to DED. For example, multiple large-scale studies have now confirmed the association between thyroid dysfunction and DED, warranting its reclassification as a consistent risk factor.¹⁴ Similarly, the well-documented anticholinergic burden of many medications has solidified their status as consistent modifiable risk factors. The upgrade of these factors to consistent evidence aligns with the aforementioned age-related pattern, as conditions such as thyroid dysfunction and anticholinergic medication use become more common with advancing age. The downgrading of hormone replacement therapy and air pollution reflects a more nuanced evidence base rather than a contradiction in epidemiological findings. For hormone therapy, subsequent studies have revealed complex, context-dependent effects that vary by formulation, duration, and patient characteristics, tempering earlier conclusions.¹⁵ For air pollution, while the association with DED remains robust, evidence on specific pollutants and exposure thresholds has proven more heterogeneous than initially acknowledged.¹⁶

The Expansion of Modifiable Risk Factors

The reclassification of rosacea, pterygium, and psychiatric conditions from non-modifiable to modifiable marks an important conceptual advance. For rosacea and pterygium, this change in status recognizes that these conditions are treatable and that effective management can reduce the risk of DED.^17,18 For psychiatric conditions, the reclassification acknowledges that targeted mental health interventions could improve DED outcomes, although the evidence base still remains at the probable level.¹⁹

Beyond these specific updates, the evolution from TFOS DEWS II to DEWS III reflects a general trend toward greater granularity and clinical utility. Ultimately, the risk-factor reclassification of these conditions from non-modifiable to modifiable broadens the scope of actionable interventions and underscores the interconnectedness of DED with other treatable conditions.^17,19

The New Subtype Classification and Its Implications

The refined subtype classification introduced in DEWS III moves beyond the binary aqueous-deficient/evaporative model to include three broad etiological categories: tear film component deficiencies, eyelid anomalies, and ocular surface abnormalities.⁷ This methodological framework provides a foundation for more targeted, mechanism-based management. When combined with the updated diagnostic thresholds introduced in the TFOS DEWS III Diagnostic Methodology report³ and the comprehensive 4-quadrant risk-factor matrix, which this study has reorganized and transformed into a practical table format based on the level of evidence certainty, presented as Table 2. This methodology equips clinicians with the tools required to achieve optimal diagnostic precision, deliver personalized treatment, and improve patient outcomes. Specifically, this practical table format helps clinicians be more aware of modifiable and non-modifiable risk factors based on the level of evidence certainty, thereby allowing them to focus more effectively on the risk factors during patient evaluations.

Research Priorities Emerging from the New Framework

The DEWS III framework outlines several priorities for future research:

1. Longitudinal studies tracking the natural history of MGD from midlife through old age to better understand its progression and identify optimal intervention windows.

2. Intervention trials examining the effectiveness of early treatment for subclinical MGD in preventing symptomatic DED.

3. Health economics research evaluating the cost-effectiveness of widespread meibomian gland screening in primary care settings.

4. Mechanistic studies elucidating the pathways linking newly identified risk factors (eg, gut microbiome, specific nutritional deficiencies) to DED.

5. Population-based studies in underrepresented regions aiming to refine prevalence estimates and identify region-specific risk factors.

The DEWS III report underscores significant progress in clinical trial design for DED, noting that aligning treatment mechanisms with specific patient subpopulations has improved the success rate of regulatory approvals (Figure 6 in the DEWS III Executive Summary).⁶ This development underscores the importance of the refined risk-factor and subtype classifications presented in this analysis, which provide a foundation for identifying responsive patient groups in future trials. These research objectives expand upon the milestones identified in the DEWS II report, which previously called for studies of younger populations, investigations into digital device use, and exploration of climate and environmental factors.²

Limitations

This analysis is limited to the risk-factor classifications outlined in the TFOS DEWS II and DEWS III reports and does not include a systematic review of primary studies or the literature. Furthermore, because the categorization of risk factors reflects expert consensus, it may not capture all individual empirical nuances of the broader evidence base. Finally, as clinical research on the ocular surface continues to advance, certain risk factors will inevitably require reclassification as new epidemiological evidence emerges, reflecting an evolving clinical and scientific landscape.

Conclusion

The transition from TFOS DEWS II to DEWS III marks a significant evolution in understanding DED risk factors, reflecting a decade of accumulated epidemiological and clinical evidence. This comparative analysis has identified several key changes with important implications for clinical practice, research priorities, and healthcare policy.

The DEWS II meta-analysis found that the prevalence of dry eye increases with age, by 2.0–10.5% per decade, depending on the diagnostic criteria used, and that clinical signs increase more rapidly than symptoms.² The DEWS III framework significantly refines this paradigm by expanding the risk-factor matrix and, most notably, reclassifying MGD from a non-modifiable to a modifiable risk factor. This reclassification represents not merely a conceptual update but a definitive paradigm shift that alters the clinical approach to DED. Rather than viewing MGD as an unchangeable consequence of aging, the new guidelines position it as a critical target for early screening, preventive management, and true disease modification. This study incorporates the updated diagnostic criteria and the comprehensive 4-quadrant risk-factor matrix presented in DEWS III, which has been reorganized and transformed by this study into a practical table format based on the level of evidence certainty (Table 2). By rearranging and transforming this matrix into a table format, this study provides a clear perspective on both modifiable and non-modifiable risk factors by the level of evidence certainty, enabling clinicians and researchers to focus more effectively on the risk factors that can be applied across different settings, such as patient evaluations and research initiatives. When applied in combination, these tools equip researchers and clinicians with a framework to achieve optimal diagnostic precision and to facilitate the delivery of enhanced personalized patient care. Given that the vast majority of dry eye cases are predominantly driven by tear-film evaporation related to underlying eyelid anomalies, integrating routine meibomian gland evaluation into standard care even for asymptomatic patient groups, is clinically essential.

Ultimately, the transition from TFOS DEWS II to DEWS III is more than an incremental update; it is an evolution, signifying a fundamental reconceptualization and a shift in understanding of DED as a complex, multifactorial condition in which modifiable risk factors, especially MGD, are central. By outlining how the risk-factor landscape has evolved, this analysis provides a structured comparative framework to help clinicians, researchers, and educators navigate the transition from DEWS II to DEWS III and apply these insights to improve the prevention, detection, and management of dry eye disease.

Funding Statement

There is no funding to report.

Author Contributions

R.A.B is the sole author and has made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; has agreed on the journal to which the article has been submitted; and agrees to be accountable for all aspects of the work.

Disclosure

The author declares no competing interests.