The editorial accompanying TFOS DEWS III presents this workshop as the latest stage in a structured international effort to standardize how dry eye disease is understood and managed. It begins with the role of the Tear Film & Ocular Surface Society, described as a nonprofit organization created to advance research, literacy, and education in the scientific field of the tear film and ocular surface, and places dry eye disease at the center of that mission. In the editorial, dry eye disease is framed as a highly prevalent disorder that affects hundreds of millions of people worldwide and remains a leading reason for visits to eye care practitioners. Its burden is also presented as extending well beyond ocular irritation alone, because in moderate or severe forms it is associated with significant pain, role limitations, low vitality, and poor general health. This opening perspective explains why the TFOS workshops have been positioned not simply as literature reviews, but as evidence-based attempts to organize a rapidly evolving field around shared definitions, clearer diagnostic pathways, and more coherent treatment strategies. The editorial recalls that TFOS organized the original Dry Eye WorkShop in 2005 with the explicit goal of providing an evidence-based critical review of the definition, classification, epidemiology, diagnosis, management, and research techniques of dry eye disease. That first workshop involved 58 members from 11 countries and 7 subcommittees, and its 2007 report is described as a landmark in the history of dry eye research and treatment. The editorial reinforces that status by reporting that respected experts viewed the original TFOS DEWS report as an authoritative resource for clinicians and researchers seeking to understand contemporary thinking across the dry eye field. It then describes the impact of that first report as unprecedented. According to the editorial, it promoted greater international awareness of external eye diseases, enhanced governmental funding for tear film and ocular surface research, stimulated the development of therapeutic drugs and diagnostic devices, and influenced the design and conduct of clinical trials for novel dry eye treatments. The scale of that influence is further underlined by the statement that the number of peer-reviewed dry eye publications in the nine years after the first report doubled relative to the previous ten years. This rapid expansion of knowledge led to TFOS DEWS II, which the editorial describes as involving 150 experts from 23 countries, 12 subcommittees, and almost two and a half years of work. The 2017 report is then presented as even more impactful than the original 2007 publication. Among the developments specifically highlighted in the editorial are the creation of an evidence-based single-sentence definition of dry eye disease, a reclassification designed to improve patient care, identification of the core mechanism of disease, recognition that evaporative dry eye is the most common form of dry eye, recognition that obstructive meibomian gland dysfunction is the major cause of evaporative disease, recognition of the importance of iatrogenic dry eye, and identification of the best evidence-based approach for diagnosis and treatment. Against this background, TFOS DEWS III is introduced as the necessary response to another major increase in research output. The editorial states that more than 8000 peer-reviewed articles on dry eye disease were published during the following six years, and presents this as the immediate reason why TFOS launched DEWS III in November 2023. Its mission, as described in the editorial, was to update TFOS DEWS II recommendations on dry eye subclassification, diagnostic methodology, and management and therapy. At the same time, TFOS DEWS III added a Digest intended to highlight advances in epidemiology, sex, gender, and hormones, pathophysiology, tear film, pain and sensation, iatrogenic dry eye, and clinical trials. The editorial therefore portrays DEWS III not as a single document with a narrow technical purpose, but as a coordinated package built to connect updated clinical guidance with a broader interdisciplinary synthesis. It also emphasizes the process by which this new consensus was developed. TFOS DEWS III involved 80 experts from 18 countries and relied on an evidence-based approach together with open communication, dialogue, and transparency to reach global consensus on multiple aspects of dry eye disease. In this way, the editorial contributes a form of scientific framing rather than detailed clinical instruction. It explains why a new consensus was needed, why the field had reached another point of revision, and why the resulting documents claim international relevance. The closing sections reinforce the sense of continuity and institutional memory around the workshop series. The editorial expresses gratitude to Anthony J. Bron, identified as the Chair of the original TFOS DEWS, for laying the foundation of the TFOS Workshop series, and acknowledges the individuals whose organizational and illustrative contributions helped make TFOS DEWS III possible. It also dedicates the report to four pioneers in tear film and ocular surface research: Claes H. Dohlman, Gary N. Foulks, Michael A. Lemp, and Juan Murube del Castillo. Read as an introduction, the editorial positions TFOS DEWS III as both a scientific update and a landmark moment in the continuing maturation of dry eye research. Its central message is that dry eye disease remains an extremely prevalent and clinically important ocular disorder, that previous TFOS workshops had already changed the field in meaningful ways, and that the volume and breadth of new evidence had become large enough to require a further international, evidence-based synthesis.

Diagnostic Methodology

The TFOS DEWS III Diagnostic Methodology report reframes dry eye disease as a condition that must be approached through a standardized clinical pathway, because consistency in diagnosis is presented as essential both for patient reassurance and for comparability across practitioners and health systems. The report revises the TFOS DEWS II definition by explicitly stating that dry eye is a multifactorial, symptomatic disease characterized by loss of homeostasis of the tear film and or ocular surface, with tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities identified as etiological factors. In doing so, it preserves several core principles while sharpening their clinical implications. Dry eye is reaffirmed as a disease rather than a syndrome, a distinction the report links to advances in understanding of diagnostic features, disease progression, and response to specific treatments. At the same time, it is described as necessarily symptomatic, which means that ocular surface signs alone are not sufficient to define dry eye disease. The report is particularly careful on this point. Ocular surface abnormalities without symptoms may indicate ocular surface disease, but not dry eye disease specifically, while symptoms without clinically meaningful signs may also arise from other conditions. This conceptual position is illustrated by the diagram on page 3, where dry eye is shown as the overlap between signs and symptoms, with differential diagnoses occupying adjacent areas and with coexistence between dry eye and other ocular surface or pain-related disorders clearly acknowledged. The document also stresses that vision-related complaints belong within the symptom profile of dry eye disease. It explains that tear film destabilization can disrupt the smooth refractive surface between blinks, producing light scatter and visual fluctuation, while surface damage can impair corneal transparency. For that reason, visual disturbance is treated not as an accessory complaint but as one component of the symptomatic burden of dry eye disease.
A major contribution of the report is its insistence that diagnosis must begin with differential diagnosis rather than with isolated test results. The authors describe both symptoms and signs of dry eye disease as heterogeneous and state that the differential diagnosis is extensive, encompassing much of ocular surface disease and even some non-ocular surface disorders. The large schematic on page 4 groups these differentials anatomically and emphasizes that several disorders can mimic dry eye, coexist with it, or even act as triggers for it. The text highlights eyelid-related disorders such as anterior blepharitis, meibomian gland dysfunction, chalazion, hordeolum, entropion, ectropion, trichiasis, floppy eyelid syndrome, blepharospasm, ocular rosacea, Bell’s palsy, and canaliculitis as causes of symptoms that may resemble dry eye. Conjunctival and corneal disorders are also given substantial weight. A careful history is recommended especially in patients with contact lens wear, multiple eye drops, or toxic exposure, because these factors may change the pattern of ocular surface staining and redirect diagnosis toward medication toxicity, limbal stem cell deficiency, contact lens-related disease, superior limbic keratoconjunctivitis, or other pathologies. The report also reviews allergic, viral, and bacterial conjunctivitis, cicatrizing conjunctivitis, conjunctivochalasis, pinguecula, pterygium, conjunctival concretions, neurotrophic keratitis, corneal dystrophies and degenerations, bullous keratopathy, infectious keratitis, Thygeson superficial punctate keratitis, limbal stem cell deficiency, ocular neuropathic pain, and a range of non-ocular surface disorders including refractive problems, digital eye strain, intermittent angle closure, scleritis, uveitis, thyroid eye disease, carotid cavernous fistula, nasolacrimal disorders, sinusitis, and headache syndromes. The report’s message is not merely that these diagnoses exist, but that missing them can delay appropriate treatment and worsen outcomes. It therefore recommends a detailed anterior segment examination when history suggests a masquerading condition and proposes focused triage questions about pain versus discomfort, facial flushing or mouth dryness, timing and triggering events, whether vision improves after blinking, asymmetry between eyes, and the presence of itching, swelling, crusting, or discharge. This history-taking model is intended to prevent premature labeling of ocular symptoms as dry eye before more specific causes have been excluded.
The report also places strong emphasis on associated and risk factors, not as secondary background information, but as elements that can help explain etiology, subtype, comorbidity, and even discordance between symptoms and signs. Dry eye is described as both multifactorial and heterogeneous, and the report notes that more than 200 associated factors have been described in the literature. It explicitly cautions that not all are necessarily causal and that some are linked more strongly to symptoms while others are linked more strongly to signs. Even so, the document argues that systematic collection of these factors is clinically useful because many are modifiable and may inform prevention, education, and management choices. The figure on page 9 visually organizes consistent and probable associated factors, while the text recommends using a questionnaire before consultation to capture them efficiently. This approach fits the broader logic of the report, which repeatedly resists reducing dry eye disease to a single test result or a single symptom score. In the same section, the report discusses symptom patterns and acknowledges that patients with dry eye often report grittiness, burning, dryness, scratchiness, watery eyes, and variable severity through the day. Yet it also underscores that symptoms alone are an unreliable guide to biological status. The section on discordance between signs and symptoms states that poor correlation is well established and summarizes multiple reasons for it: measurement error, the dynamic nature of disease, environmental effects, differences in the time window covered by symptom questionnaires and sign-based tests, the coexistence of different etiologies within one patient population, the fact that common clinical tests do not directly measure all core mechanisms such as neurosensory abnormalities and inflammation, the presence of comorbid ocular surface disease, the asymptomatic nature of some conditions such as meibomian gland dysfunction, and the uneven effects of treatments on symptoms and signs. The report further notes that certain patient characteristics are associated with symptoms outweighing signs, while others are associated with fewer symptoms than expected from ocular findings. The practical implication is clear: clinicians should not assume that severe symptoms always reflect severe surface damage, nor that limited symptoms exclude important disease. This is one reason why the report pushes toward a formalized diagnostic sequence rather than reliance on clinical impression alone.
That standardized sequence begins with symptom confirmation, and here TFOS DEWS III makes one of its clearest methodological changes. After reviewing the large number of available dry eye questionnaires and their uneven comparability, the report recommends the OSDI-6 as the single standardized symptom-screening questionnaire for diagnostic purposes. The text explains that the OSDI-6 was developed as a shortened form of the original OSDI in order to reduce response burden while maintaining performance. It contains six questions, uses a one-month recall period, and can be scored rapidly by summing the item scores. The diagnostic cut-off is a summed score of at least 4, as shown in the table on page 10. The report presents the OSDI-6 as more repeatable than the full OSDI or the DEQ-5, while still yielding comparable outcomes and requiring less time to complete and score. It also notes that the abbreviated format may be more suitable for children because it requires less time and assistance. Importantly, the report does not claim that the OSDI-6 alone diagnoses dry eye disease. Instead, it functions as the standardized symptom gateway into the rest of the algorithm. The purpose is consistency: because different questionnaires are not interchangeable, one instrument is needed if clinicians are to classify patients in a comparable way across settings. Other questionnaires may still be useful for supplementary exploration of risk factors, quality of life, or treatment selection, but the OSDI-6 is the one recommended for diagnostic screening.
After symptoms have been established, the report defines a homeostasis-based sign battery for confirmation of disease. The diagnostic logic is summarized in the abstract and further refined in the section on key methodological changes. A diagnosis of dry eye requires a positive symptom screen together with evidence of loss of tear film and or ocular surface homeostasis. The report identifies three principal sign domains for this purpose: tear film instability, hyperosmolarity, and ocular surface staining. A positive diagnosis can be made when the OSDI-6 threshold is met together with a non-invasive breakup time below 10 seconds, or tear hyperosmolarity at or above 308 mOsm/L in either eye or an interocular difference greater than 8 mOsm/L, or ocular surface staining above the stated thresholds. The staining component is broader than corneal fluorescein staining alone. The report specifically includes corneal fluorescein staining, conjunctival lissamine green staining, and lid margin lissamine green staining, and argues that full staining assessment is important because limiting evaluation to the cornea alone markedly reduces sensitivity. It also states that the overall diagnostic approach is robust. The analysis summarized in the report indicates that although only one positive homeostasis sign is needed to support diagnosis, at least two signs need to be assessed to safely exclude a diagnosis, because evaluating only a single sign can miss patients who would otherwise meet criteria. The text also notes that omission of either non-invasive breakup time or osmolarity has only a minor effect on prevalence estimates, which is part of the rationale for simplifying the revised algorithm for clinical practice. These changes are presented not as a conceptual reinvention, but as an evidence-based refinement of the TFOS DEWS II approach.
The most forward-looking feature of the Diagnostic Methodology report is its move away from a simple aqueous-deficient versus evaporative classification and toward an etiological driver-based subclassification. Once dry eye disease has been diagnosed, the report recommends identifying the dominant drivers in the individual patient so that management can target the mechanisms actually present. In the abstract and later summary sections, these drivers are divided into tear film deficiencies, eyelid anomalies, and ocular surface abnormalities. Tear film deficiencies include lipid, aqueous, and mucin glycocalyx components. Eyelid anomalies include blink and lid closure problems and lid margin disease. Ocular surface abnormalities include anatomical misalignment, neural dysfunction, ocular surface cell damage or disruption, and primary inflammation or oxidative stress. The example test sequence described in Table 7 is explicitly ordered from least to most invasive in order to preserve measurement integrity. It begins with symptoms, then moves through blink and lid closure assessment, tear meniscus height, non-invasive breakup time, anatomical lid or globe misalignment, redness, interferometry, osmolarity, lid margin examination and diagnostic expression, optional fluorescein breakup time, ocular surface staining, meibography, and neural testing where indicated. The report states that diagnosis and subtype assessment may be performed in a single visit if time allows or separated across two visits, but that tests should always be ordered from least to most invasive. This is where the report’s practical ambition is most visible. It is not satisfied with defining dry eye disease at a high level; it tries to translate that definition into a reproducible clinical workflow that connects symptom screening, differential diagnosis, homeostasis testing, subtype identification, and later management decisions. In that sense, the report lays the methodological foundation for the whole TFOS DEWS III framework.

Digest

The TFOS DEWS III Digest serves as the interdisciplinary scientific backbone of the new workshop, updating the evidence published since TFOS DEWS II and explicitly linking that evidence to diagnostic methodology, disease subtype, and management. Its stated purpose is not to redefine dry eye disease on its own, but to synthesize the main advances across seven domains that shape how dry eye should now be interpreted: sex, gender, and hormones; epidemiology; pathophysiology; tear film; pain and sensation; iatrogenic dry eye; and clinical trial design. This gives the document a distinct role within the overall TFOS DEWS III package. Whereas the diagnostic and management reports are organized around clinical decisions, the Digest explains why those decisions had to change by assembling the scientific developments that occurred between 2017 and 2024. At the level of broad conclusions, the report states that sex- and gender-related differences significantly influence the ocular surface through hormonal effects, sex chromosomes, sex-specific autosomal factors, epigenetics, care-seeking behaviors, and service use; that epidemiologic patterns vary depending on diagnostic criteria; that pathophysiologic distinctions between aqueous-deficient and more evaporative forms have become clearer; that tear film research is increasingly focused on dynamic interactions and biomarkers; that ocular pain perception depends on both peripheral and central neural mechanisms; that iatrogenic dry eye can arise from medications, contact lenses, and procedures; and that clinical trials increasingly aim to align outcomes with dry eye subtype and therapeutic mechanism. In this sense, the Digest supports a more differentiated view of dry eye disease than a simple symptom-based or binary classification model.
One of the most substantial contributions of the Digest is its treatment of sex, gender, and hormones as central biological and clinical determinants rather than background modifiers. The report describes significant sex-related differences in the lacrimal gland, meibomian gland, cornea, and eyelid, and states that these differences may contribute to the higher prevalence of dry eye disease in females. In the lacrimal gland, the report summarizes evidence that sex influences gene expression, tissue morphology, and inflammatory responses, including in murine models of Sjögren-related disease, and notes that female human lacrimal glands show a higher frequency of multiple degenerative changes with aging. In the meibomian gland, the report emphasizes that sex-related patterns are complex and sometimes inconsistent, even though meibomian gland dysfunction remains a major cause of dry eye. It also notes sex-related differences in corneal thickness, sensitivity, nerve regeneration, epithelial healing, and blinking behavior. Hormonal regulation is treated in equally specific terms. The report states that androgens are extremely important in the regulation of the ocular surface and adnexa, and that androgen deficiency is associated with both aqueous-deficient and evaporative dry eye. It also reviews more mixed findings for estrogens, including animal studies, aromatase inhibitor observations, and the absence of benefit in one recent topical estradiol trial. Progesterone is described as a possible modulator of ocular discomfort and pain, while insulin-like growth factor and insulin are linked to tear film and ocular surface health, particularly in the context of diabetes. Thyroid eye disease is presented as another important intersection between endocrine and ocular surface disease. The figure on page 6 is especially useful because it visually summarizes the proposed mechanisms linking thyroid eye disease to dry eye, including orbital inflammation, mechanical effects, and thyroid hormone impairment, together with the associated clinical findings such as wide open eye, superior limbic keratoconjunctivitis, low tear film breakup time, incomplete blinking, punctate keratitis, corneal opacity, conjunctival hyperemia, and meibomian gland dysfunction. The report also remains cautious where evidence is still limited, especially regarding the ocular effects of gender-affirming hormone therapy. It states that both sex and gender influence dry eye risk and presentation, but that there is still limited information about the impact of gender-affirming hormone therapy on vision and ocular surface health.
The epidemiology section reinforces the idea that dry eye disease cannot be described by a single prevalence figure. Instead, the report shows that prevalence varies substantially according to how disease is defined. The meta-analytic framework includes several diagnostic categories, among them Women’s Health Study criteria, symptomatic disease, symptoms plus signs, criteria aligned with TFOS DEWS II, clinical diagnosis, and both any and clinically significant meibomian gland dysfunction. The table on page 9 summarizes the prevalence ranges observed across these categories, and the report repeatedly emphasizes that not all patterns increase with age or show the same sex distribution. Broadly, the report states that studies using Women’s Health Study criteria show an increase with age and a higher frequency in women, while clinically diagnosed dry eye also shows female predominance but less obvious age dependence. Symptom-based and sign-plus-symptom definitions yield different distributions again, and meibomian gland dysfunction appears particularly age-related, with older males more likely to show meibomian gland dysfunction than older females when any gland dysfunction is considered. The Digest also highlights that data in people under 20 years of age remain limited. In this age group, rates of clinically diagnosed dry eye and clinically significant meibomian gland dysfunction are lower than in adults, but symptom reporting can still be high, which the report notes is not specific enough by itself to define dry eye disease. Beyond prevalence, the report reviews incidence and natural history. It states that annual incidence appears to be higher in women than men and tends to increase with age, but also notes that incidence estimates are difficult because symptoms may fluctuate over time and because claims data can be influenced by reimbursement and treatment changes. Longitudinal evidence is described as limited. Even so, the report states that there is reasonable evidence that signs may develop before symptoms in untreated disease, a point that has implications for both case finding and timing of intervention. The epidemiology section also updates the field’s understanding of risk factors. The report identifies conclusive and probable factors across systemic disease, ophthalmic disease, surgery and procedures, medications, environment, demographics, and lifestyle, and recommends systematic collection of these factors in practice because they may help clarify etiology and identify disease drivers in the individual patient.
In pathophysiology and tear film biology, the Digest helps explain why TFOS DEWS III moved toward etiological drivers rather than relying only on the older aqueous-deficient versus evaporative distinction. The report states that research published since TFOS DEWS II has clarified differences between and within aqueous-deficient and evaporative forms, while also expanding the range of relevant stresses and mechanisms. Evaporative disease is described as commonly characterized by a more muted inflammatory response at the ocular surface, meibomian gland dysfunction, and possible phenotypic changes in corneal epithelial cells. At the same time, the report emphasizes a growing role for metabolic, hormonal, physical, neural, and cellular stresses, including hyperosmolarity, mitochondrial stress, and neurogenic inflammation. This broadens the conceptual model of dry eye beyond tear deficiency alone. The tear film section aligns with that shift by emphasizing interactions among tear lipids, proteins, mucins, and cellular responses rather than treating the tear film as a static structure. The report states that advances in tear film research support new approaches to understanding pathogenesis and identifying biomarkers, including microRNAs. It also signals a more critical approach to measurement, highlighting the need for reproducible methods and biologically meaningful markers that can better distinguish subtypes and treatment responses. This theme then overlaps with the pain and sensation section, which moves the field beyond the assumption that symptoms are simply a direct reflection of tear deficiency or epithelial damage. The Digest states that ocular pain perception is linked to the structural integrity of corneal nerves, the functional capacity of neurons, and the activity of the peripheral and central nervous systems. This is important because it offers a mechanistic basis for the symptom-sign mismatch that appears throughout dry eye research and clinical practice. The report therefore supports a more integrated view in which tear film instability, inflammation, neural dysfunction, and ocular pain are connected but not interchangeable.
The remaining sections on iatrogenic dry eye and clinical trial design show how the field is becoming both more clinically aware and more methodologically demanding. The Digest states that iatrogenic dry eye can result from medications, contact lenses, and surgical procedures, and frames this not as a marginal issue but as one of the new risk domains that should influence both history taking and management planning. In parallel, the clinical trial design section is described as moving toward closer alignment between endpoints, dry eye subtypes, and therapeutic mechanisms. Rather than assuming that all dry eye patients form a single responsive population, the report indicates that newer studies increasingly recognize disease heterogeneity and the need to match trial design to the mechanism targeted by the intervention. This is one of the most important overarching messages of the Digest. It does not argue that dry eye disease has become simpler or more unified. On the contrary, it presents dry eye as a multifactorial condition whose epidemiology, biology, symptoms, and treatment responses all depend on the interplay of subtype, risk factor burden, systemic context, and mechanism. For that reason, the Digest is not merely supplementary reading. It is the document that makes the logic of TFOS DEWS III intelligible: it explains why the updated diagnostic report insists on better subclassification, why the management report is organized around etiologic drivers, and why the future of dry eye research is likely to depend on better biomarker definition, better neural phenotyping, and better-designed subtype-specific trials.

Management and Therapy

The TFOS DEWS III Management and Therapy report presents treatment as a direct extension of the new diagnostic and subclassification framework, rather than as a generic escalation ladder applied in the same way to all patients with dry eye disease. Its stated aim is to provide a contemporary overview of the evidence on management, to build an evidence-based algorithm that helps clinicians decide when to use available therapies, and to determine whether there is evidence supporting each option for one or more of the updated TFOS DEWS III subclasses. From the outset, the report makes clear that management should be tied to the presenting signs, symptoms, and diagnostic testing that identify the relevant etiological drivers in the individual patient. It also notes that many treatments overlap in mechanism and may act across more than one broad management category, a point that becomes important throughout the report because dry eye disease is repeatedly treated as a multifactorial condition that often requires more than one therapeutic approach. The abstract summarizes this philosophy clearly. First-line management is described as focusing on methods to replenish, conserve, and stimulate the tear film, with ocular supplements remaining the cornerstone of treatment. Meibomian gland dysfunction, identified as a primary contributor to dry eye disease, is typically approached with warm compresses and a wide variety of in-office interventions, including technologies that warm the eyelids, intense pulsed light therapy, low-level light therapy, and other emerging procedures. Lid hygiene approaches are also included, such as lid wipes, anti-Demodex therapies, blepharoexfoliation, and topical antibiotics. Beyond these approaches, the report states that dry eye associated with particular etiological drivers may benefit from anti-inflammatory therapy, including topical and oral corticosteroids, T-cell immunomodulatory drugs, and a broad range of pharmacological agents, as well as biologic tear substitutes such as autologous serum and platelet-rich plasma. Emerging options are said to include neuromodulation through nasal neurostimulation and other novel pharmacological treatments, while advanced options for severe or refractory disease include amniotic membrane grafts and more complex surgical methods. The report also explicitly incorporates lifestyle modifications, including optimized blinking, dietary supplementation, and environmental adjustment, and emphasizes that patient education and adherence remain essential for sustained symptom relief. This overall structure is therefore not simply a catalogue of therapies. It is an attempt to align therapies with pathophysiology and to support targeted management of the dry eye subtype or subtypes present in a given individual.
A consistent theme in the report is that treatment cannot be separated from lifestyle and chronic disease education. The lifestyle section states that lifestyle factors play a critical role in both the development and management of dry eye disease, influencing ocular health as well as quality of life. Modern behaviors such as poor sleep, cosmetic use, elective ocular and periocular procedures, and systemic medications are described as capable of exacerbating or creating dry eye symptoms. Excessive digital device use is singled out as a major contributor because reduced blink rate and incomplete blinking during screen use can induce tear film instability, increased evaporation, and ocular surface damage. Diet is also discussed, with diets rich in omega-3 fatty acids described as potentially improving tear quality and reducing inflammation, while diets low in essential nutrients may contribute to systemic inflammation and worsening ocular surface disease. Environmental conditions such as humidity, airflow, pollutants, and allergens are presented as additional influences on the ocular surface. The report then translates these observations into practical management concepts, including avoidance of known symptom triggers, local humidity control, physical protection of the ocular surface, and a broad view of lifestyle modification across all dry eye subtypes. The text is careful not to isolate these elements as minor adjuncts. Instead, lifestyle advice is framed as relevant across the entire management spectrum, regardless of subtype or other therapies selected. This makes the management report notably broader than a drug or device review. It repeatedly brings treatment back to the chronic, multifactorial, and behavior-sensitive nature of dry eye disease.
The section on tear insufficiency further illustrates how TFOS DEWS III organizes therapy by mechanism and by component of tear film dysfunction. Tear supplements and stabilizers are described as agents that enhance and or stabilize the tear film and remain a cornerstone of management for tear insufficiency or dysfunction regardless of underlying etiology. Their overall goal is presented as restoration of tear film and ocular surface homeostasis and interruption of the cycle of instability, hyperosmolarity, inflammation, and epithelial damage. The report then reviews several formulation classes, including aqueous viscosity-enhancing agents, lipid-containing formulations for evaporative disease, tear stabilizers such as perfluorohexyloctane, hyaluronic acid-based products, osmoprotectants, preservatives and preservative-free strategies, and combinations of polymers designed to improve lubrication, retention, and hydration. Across these formulations, the report stresses that efficacy may depend on the full composition of the product rather than on one ingredient in isolation. It also recognizes that selection remains difficult because head-to-head evidence is limited and because different products may be better suited to different tear film deficiencies. Even within this apparently familiar treatment area, TFOS DEWS III remains closely tied to subtype logic. Lipid-containing supplements are presented as particularly relevant to lipid deficiency, while the report also notes that one month of regular use may be sufficient to determine symptomatic benefit, whereas signs may require a longer period of treatment to improve. This kind of distinction reflects the broader effort of the management report to move from generalized dry eye care toward a more explicit driver-based prescribing logic.
The same logic continues across tear conservation and tear restoration strategies. Contact lenses are discussed both as a potential risk factor for dry eye and as a therapeutic tool in selected cases. Moisture-retaining spectacles are described as increasing periocular humidity and reducing tear evaporation. Punctal occlusion is presented as an interventional option for moderate to severe aqueous-deficient dry eye, although the report also notes limitations in the evidence and the possibility of adverse reactions. Across these sections, the authors repeatedly point out that some established approaches are widely used in practice but still lack the degree of robust comparative evidence that would allow confident ranking. That caution becomes even more important in the sections on newer therapies. The report includes biologic and regenerative approaches, epithelial promoters, neurotrophic strategies, and novel topical agents, but it rarely presents them as universally established solutions. Instead, it distinguishes between approaches that already have substantial clinical support and those that are still emerging or still require higher quality evidence. This restrained tone is especially relevant to the broader message of the report. TFOS DEWS III does not present management as a fixed hierarchy in which every patient should progress through the same sequence. It presents a framework in which multiple pathogenic drivers may coexist, multiple therapies may need to be combined, and treatment choice should be justified by a mechanism of action that is relevant to the patient’s individually identified subtype profile.

Silk proteins

Within the section on epithelial promoters and ocular surface regenerative strategies, the report includes a specific subsection on silk-derived protein, placing it among newer pharmacological treatments under investigation for dry eye disease. The rationale given for this approach is closely tied to the biology of the tear film. The report states that tear film mucins enhance ocular surface wetting because of their amphiphilic chemistry and also provide natural bioactivity that helps maintain a healthy ocular surface. Silk-derived protein 4, abbreviated SDP-4, is described as a naturally derived protein obtained from the Bombyx mori silkworm cocoon. According to the report, it behaves in a mucin-like way by improving wetting of the ocular surface and by acting as a replacement for demulcents and surfactants that may have higher toxicity profiles. The section then summarizes the preclinical basis for interest in this material. In vitro studies are reported to show that silk fibroin can modulate proinflammatory signaling by inhibiting the NF-kB pathway. The report also cites a murine dry eye model in which aqueous silk fibroin protein improved clinical outcomes, including increased tear production, decreased corneal irregularity, inhibition of epithelial cell detachment, and increased goblet cell density, together with reduced inflammatory cytokine gene expression and secretion of intercellular adhesion molecule 1, MMP-2, and MMP-9. On this basis, silk-derived protein is presented as a biologically active candidate rather than simply another lubricant vehicle.
The clinical evidence described in the same subsection remains much more limited and is presented cautiously. The report identifies one randomized in-human clinical trial using SDP-4 in participants with moderate-to-severe dry eye disease. In that study, participants were dosed twice daily for up to 84 days in a double-masked, randomized, parallel-group, serial cohort design. The report states that participants receiving eye drops containing 1% SDP-4 showed a significant increase in tear breakup time from baseline, and that this increase was significantly greater than the change observed in the vehicle control group. It also notes that patient symptoms were reduced, but in a manner similar to the control group, and that more than 90% of participants found the formulation comfortable. The wording of the report is important here. It does not describe silk-derived protein as a proven standard therapy, nor does it claim superiority across all outcomes. What it does show is that TFOS DEWS III considers SDP-4 a credible emerging option with a biologically plausible mechanism, supportive preclinical evidence, and early human evidence of improved tear film stability and good tolerability in moderate-to-severe disease. Within the overall architecture of the management report, this places silk-derived protein among the newer regenerative or tear film-supportive approaches that may become more relevant as subtype-driven management continues to evolve.
Read as a whole, the Management and Therapy report transforms TFOS DEWS III from a diagnostic consensus into a treatment framework. Its central message is that treatment should no longer be chosen only by broad labels such as mild or severe dry eye, or only by the older aqueous-deficient versus evaporative division. Instead, management should be linked to the identified etiological drivers, should usually combine more than one intervention when multiple mechanisms coexist, and should integrate lifestyle, tear film support, eyelid management, anti-inflammatory therapy, regenerative approaches, and in selected cases advanced or emerging therapies. The inclusion of silk-derived protein within this framework is therefore significant, not because the report presents it as definitive, but because it exemplifies the direction of TFOS DEWS III as a whole: moving toward more mechanism-aware, biologically informed, and subtype-sensitive treatment selection.

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