Ocular Surface Changes Associated with Ophthalmic Surgery

The aim of this review is to summarize the results of a consensus meeting held by a group of experts in dry eye disease (DED) to discuss the importance of tear substitutes in the treatment of DED. The meeting focused especially on the main characteristics of lacrimal substitutes, the development of in vitro models to investigate DED pathophysiology and treatment, the importance of conducting rigorous clinical trials, the requirements of the upcoming European Legislation on medical devices, the advances in the formulation of safer preservatives, the peculiarities of treatment in younger subjects, and the importance of an updated terminology for lacrimal substitutes. A literature search was conducted using MEDLINE, with different combinations of pertinent keywords, depending on the subject under discussion, such as "dry eye disease"; "tear substitutes"; "in vitro models"; "ocular surface"; "clinical trials"; "European Regulation"; "preservatives" "younger patients". Also, each author included in the discussion selected articles from their personal library. Using a consensus-based method called nominal group technique to reach a conclusion and proposal for a new classification of eye drops used to improve the tear film and ocular surface epithelia, the experts also conducted a round table meeting. The new terms proposed by the authors are "wetting agents", "multiple-action tear substitutes" or "ocular surface modulators". The new classification is needed to distinguish eye drops used to improve the tear film and ocular surface epithelia, in line with the new definition of DED, which recognizes the loss of ocular homeostasis, and the creation of a vicious circle of chronic inflammation and ocular damage as fundamental aspects of DED pathophysiology. Although tear substitutes have been historically used to provide eye lubrication to the ocular surface, recent advances in the pathophysiology of dry eye disease (DED) clarified that treatment should not just focus on tear film quality or quantity, but address the loss of homeostasis of the ocular surface, blocking the vicious circle of chronic inflammation and ocular damage. Given the scant comparative evidence on tear substitutes currently on the market, further studies should focus on developing new agents, considering the advantages provided by in vitro models, importance of conducting rigorous clinical trials, availability of less harmful preservatives and obligations related to the new European legislation on medical devices. Based on the discussion of these topics, a group of experts held a consensus meeting to identify new and more appropriate terms for different tear substitutes. The proposed terms are wetting agents, multiple-action tear substitutes and ocular surface modulators. Regardless of the agent used, it is important to note that tear substitutes represent one of many options for DED treatment, which should not overlook the psychological aspects of the disease and the peculiarities of younger subjects, who seem to have a higher risk for DED, possibly related to digital devices excessive use.

Ocular surface microbiota (OSM) dysbiosis is associated with dry eye disease (DED), but the underlying mechanisms remain poorly understood. This study investigated the role of lipoteichoic acid (LTA), a Gram-positive bacterial product, in DED pathogenesis. A cross-sectional study was conducted involving 277 participants to analyze OSM composition via 16S rRNA sequencing and quantify tear LTA levels. In vitro experiments using human corneal epithelial cells (HCE-T) and in vivo mouse models were used to explore LTA-induced inflammation. The involvement of Toll-like receptor 2 (TLR2) and platelet-activating factor receptor (PAFR) was assessed using siRNAs and the PAFR antagonist Apafant. Patients with DED showed functional enrichment in LTA synthesis-related pathways in their OSM. Tear LTA levels were significantly elevated in patients with DED and correlated positively with disease risk and clinical severity. Mechanistically, LTA activated p38 MAPK and NF-κB signaling pathways via TLR2 and PAFR, upregulating pro-inflammatory cytokine expression. In mice, topical LTA administration induced corneal epithelial damage, reduced tear secretion, and caused histopathological changes. Treatment with Apafant significantly alleviated LTA-induced corneal inflammation, improved tear secretion, and preserved epithelial integrity. Our findings establish a mechanistic link between OSM-derived LTA and DED. LTA promotes ocular surface inflammation and dysfunction through TLR2 and PAFR signaling, suggesting that targeting microbial products or their receptors, such as PAFR, may offer a novel therapeutic strategy for DED.

Research progress in surgery-related meibomian gland dysfunction

Seeing through tears: Understanding and managing dry eye disease.

Background Dry eye is among the most prevalent complications following refractive surgery, significantly impacting the training and daily lives of recruits. While recent years we have witnessed some advancements in understanding the occurrence and progression of dry eye, the specific effects of refractive surgery on this condition remain unclear. This study aims to investigate the impact of refractive surgery on dry eye among 300 army recruits. Methods A series of examinations specific to dry eye were conducted on the subjects using the OSDI questionnaire and the ocular surface comprehensive analyzer. The correlation between refractive surgery and dry eye was analyzed in conjunction with dry eye symptoms and related data. Additionally, optical coherence tomography (OCT) was employed to observe fundus changes in dry eye patients, comparing those with low to moderate myopia against patients with high myopia prior to surgery. The morphology of the meibomian glands in the upper eyelid was assessed using the Keratograph 5M ocular surface analyzer, where the area of meibomian gland loss was calculated and scored, facilitating an exploration of the relationship between meibomian gland loss and dry eye. Furthermore, the dry eye detection rates of Non-Invasive Break-Up Time (NIBUT), Lipid Layer Thickness Measurement (LTMH), and basal Schirmer secretion (SIT) were calculated, and the diagnostic differences among these three methods for dry eye were analyzed. Results According to the OSDI questionnaire, 117 (39%) patients opted for SMILE, 60 (20%) for F-LASIK, and 123 (41%) for LASIK. Among the recruits, 78 (26%) were diagnosed with dry eye following refractive surgery. Single factor and multiple logistic regression analyses indicated that LASIK may serve as an independent risk factor for the development of dry eye after refractive surgery. Furthermore, the incidence of leopard-pattern fundus was significantly higher in recruits with high myopia compared to those with low to moderate myopia. Keratograph5M assessments revealed that 52.6% of patients exhibited no meibomian gland loss; 45.5% had meibomian gland loss of less than 1/3; 1.9% experienced meibomian gland loss ranging from 1/3 to 2/3; and no patients had meibomian gland loss exceeding 2/3. These results suggest that there is no direct relationship between dry eye and meibomian gland loss following refractive surgery. Additionally, the dry eye detection rate using non-invasive tear break-up time (NIBUT) was 92.6%, while the detection rate for LTMH dry eye was 91.0%. The basal Schirmer test (SIT) yielded a dry eye detection rate of 78.2%, indicating that non-invasive tear assessment methods have a higher detection rate for dry eye. Conclusions The incidence of dry eye among recruits following excimer laser corneal refractive surgery is significantly higher than that observed with other surgical methods, suggesting that it may represent an independent risk factor for dry eye post-refractive surgery. Consequently, we do not recommend the use of laser in situ keratomileusis for refractive surgery.

Dry eye is among the most prevalent complications following refractive surgery, significantly impacting the training and daily lives of recruits. While recent years we have witnessed some advancements in understanding the occurrence and progression of dry eye, the specific effects of refractive surgery on this condition remain unclear. This study aims to investigate the impact of refractive surgery on dry eye among 300 army recruits. A series of examinations specific to dry eye were conducted on the subjects using the OSDI questionnaire and the ocular surface comprehensive analyzer. The correlation between refractive surgery and dry eye was analyzed in conjunction with dry eye symptoms and related data. Additionally, optical coherence tomography (OCT) was employed to observe fundus changes in dry eye patients, comparing those with low to moderate myopia against patients with high myopia prior to surgery. The morphology of the meibomian glands in the upper eyelid was assessed using the Keratograph 5M ocular surface analyzer, where the area of meibomian gland loss was calculated and scored, facilitating an exploration of the relationship between meibomian gland loss and dry eye. Furthermore, the dry eye detection rates of Non-Invasive Break-Up Time (NIBUT), Lipid Layer Thickness Measurement (LTMH), and basal Schirmer secretion (SIT) were calculated, and the diagnostic differences among these three methods for dry eye were analyzed. According to the OSDI questionnaire, 117 (39%) patients opted for SMILE, 60 (20%) for F-LASIK, and 123 (41%) for LASIK. Among the recruits, 78 (26%) were diagnosed with dry eye following refractive surgery. Single factor and multiple logistic regression analyses indicated that LASIK may serve as an independent risk factor for the development of dry eye after refractive surgery. Furthermore, the incidence of leopard-pattern fundus was significantly higher in recruits with high myopia compared to those with low to moderate myopia. Keratograph5M assessments revealed that 52.6% of patients exhibited no meibomian gland loss; 45.5% had meibomian gland loss of less than 1/3; 1.9% experienced meibomian gland loss ranging from 1/3 to 2/3; and no patients had meibomian gland loss exceeding 2/3. These results suggest that there is no direct relationship between dry eye and meibomian gland loss following refractive surgery. Additionally, the dry eye detection rate using non-invasive tear break-up time (NIBUT) was 92.6%, while the detection rate for LTMH dry eye was 91.0%. The basal Schirmer test (SIT) yielded a dry eye detection rate of 78.2%, indicating that non-invasive tear assessment methods have a higher detection rate for dry eye. The incidence of dry eye among recruits following excimer laser corneal refractive surgery is significantly higher than that observed with other surgical methods, suggesting that it may represent an independent risk factor for dry eye post-refractive surgery. Consequently, we do not recommend the use of laser in situ keratomileusis for refractive surgery.

Background: Dry eye disease is a multifactorial disorder of the ocular surface and is a common cause of postoperative discomfort following cataract surgery, especially in the elderly population. Symptoms such as foreign body sensation, grittiness, ocular fatigue, and visual disturbance significantly affect the quality of life and patient satisfaction after surgery. Cataract surgery, being the most frequently performed ophthalmic procedure, particularly for senile cataract, can exacerbate pre-existing or subclinical ocular surface disease due to surgical trauma, corneal nerve damage, and postoperative topical medications. Early identification and management of dry eye are therefore essential to improve postoperative outcomes. Methods: This prospective comparative study included 160 patients undergoing cataract surgery, divided equally into two groups: 80 patients underwent manual Small Incision Cataract Surgery (SICS) and 80 underwent phacoemulsification. Patients were evaluated preoperatively (1 day before surgery) and postoperatively at 7, 30, and 90 days. Dry eye was assessed using the Ocular Surface Disease Index (OSDI) questionnaire, Tear Break-Up Time (TBUT), and Schirmer’s test. The incidence and severity of dry eye and ocular surface damage were compared between the two surgical techniques. Results: A significant increase in dry eye signs and symptoms was observed during the first postoperative week in both groups, evidenced by increased OSDI scores and reduced TBUT and Schirmer’s values. OSDI and TBUT showed better correlation with dry eye severity compared to Schirmer’s test. By 30 and 90 days postoperatively, tear film parameters gradually improved and returned to near-normal levels. Phacoemulsification was associated with a significantly lower incidence and severity of postoperative dry eye compared to manual SICS. Conclusion: Dry eye disease is a common but transient postoperative complication following both manual SICS and phacoemulsification. Symptoms are more pronounced in the early postoperative period, likely due to frequent use of topical medications and ocular surface toxicity and resolve as medications are tapered. OSDI and TBUT are more reliable indicators of postoperative dry eye than Schirmer’s test. Early postoperative ocular surface evaluation and the use of tear substitutes can reduce epithelial damage and improve patient comfort. Phacoemulsification causes less ocular surface disturbance and offers better postoperative patient well-being.

Actuality. Today, laser correction of refractive errors is a high-tech and safe industry in ophthalmic surgery, which provides highly predictable and stable refractive results in patients with ametropia. But at the same time, keratorefractive surgery can cause the development of induced dry eye syndrome, which will be one of the main reasons for dissatisfaction with the result of surgery in patients. Even a mild form of dry eye syndrome can significantly affect a patient's quality of life, leading to decreased performance. Purpose. To study the data of modern literature sources on the main aspects of etiopathogenesis and diagnosis of dry eye syndrome in refractive patients. Material and methods. To perform the review, we analyzed the search for literature sources on PubMed reference databases using the keywords «tear film», «dry eye syndrome», «keratorefractive surgery» according to Russian publications on the subject of the article for the period up to and including 2025. Results and discussion. An important basis for understanding dry eye syndrome is not only the etiology of the pathogenesis of the disease, but also the conduct of a qualitative diagnosis followed by ensuring the comfort of visual functions in patients with refractive profile. Conclusion. Identifying patients at risk of developing dry eye syndrome after refractive surgery allows the ophthalmologist to take the necessary measures to optimize the condition of the eye surface before surgery, which helps to obtain a portrait of a happy refractive patient. Key words: tear film, ocular surface, dry eye syndrome, keratorefractive surgery.

​ Altered homeostasis of the ocular surface microenvironment is a hallmark of dry eye disease (DED). The alpha-7 nicotinic acetylcholine receptor (α7nAChR) plays a key role in DED pathophysiology. In this study, we established a rabbit model of DED using scopolamine hydrobromide (Scop) to determine the effect of electroacupuncture (EA) on ocular surface damage in DED and to explore its underlying mechanisms.​ Methods: New Zealand White rabbits (1.5-2.0 kg) were subcutaneously administered Scop for 21 days prior to EA treatment. After 35 days, the homeostasis of the ocular surface microenvironment was evaluated using the Schirmer I test (SIT), tear break-up time (BUT), corneal fluorescein (FL) staining, and measurement of tear osmolarity. The expression levels of ACh, α7nAChR, and high mobility group box 1 (HMGB1) were detected via histopathological examination of the cornea, lacrimal glands, and conjunctiva, combined with immunohistochemistry and western blotting. Additionally, protein chip technology was used to determine the expression levels of downstream factors.​ Results: EA stimulation significantly improved the homeostasis of the ocular surface microenvironment, as evidenced by increased SIT values and BUT, reduced corneal FL intensity, and decreased tear osmolarity. It also alleviated pathological damage to the cornea, conjunctiva, and lacrimal glands; upregulated the expression of ACh and α7nAChR; and downregulated the expression of HMGB1 and related inflammatory factors. However, these changes were reversed following administration of α-Bungarotoxin.​ Conclusion: EA stimulation improves ocular surface homeostasis and reduces inflammation in DED, potentially via activation of the α7nAChR signaling pathway, which in turn inhibits the expression of HMGB1 and inflammatory factors.​.

The cornerstone of managing dry eye syndrome (DES) remains the administration of artificial tear substitutes, the selection of which is challenging due to their extensive diversity. A rational therapeutic approach necessitates accounting for the nature of ocular surface changes and the severity of DES. According to TFOS DEWS II (2017) recommendations, DES may be categorized as evaporative DES due to increased tear film instability, corresponding to mild DES as per the classification of V.V. Brzeski et al. (2016), or aqueous-deficient DES, which corresponds to moderate, severe, and particularly severe forms of DES. Furthermore, the ADES (2020) guidelines describe an additional subtype of DES linked to reduced corneal wettability associated with membrane-associated mucin deficiency (e.g., conjunctival and corneal epitheliopathy). Based on these diagnostic frameworks, the treatment of mild evaporative DES typically involves the use of lipid-based agents that stabilize the lipid layer of the tear film or artificial tear substitutes that increase viscosity to counteract the excessive aqueous component of the tear film, with products such as hyaluronic acid (HA)-based formulations. In cases of aqueous-deficient DES, the treatment tactics focus on restoring the aqueous-mucin component of the tear film by utilizing agents that enhance viscosity. Such agents are commonly delivered as fixed combinations (FC) of HA and compounds that improve the qualitative and quantitative characteristics of the tear film. For severe epitheliopathy, it is advisable to incorporate additional agents that interact with the damaged epithelium to modify the ocular surface or employ reparative agents to facilitate tissue recovery. In mixed forms of DES, FC are suitable, including formulations that simultaneously replace both the lipid and aqueous-mucin layers of the tear film, osmoprotective agents, and components that directly influence the ocular surface epithelium. KEYWORDS: dry eye syndrome, evaporation, aqueous deficiency, mucin deficiency, hyaluronic acid, polyethylene glycol, triglycerides, carbomer, dexpanthenol. FOR CITATION: Yanchenko S.V., Odilov M.Yu., Kharibova E.A., Malyshev A.V., Teshaev Sh.Zh., Davlatov S.S., Shonazarov A. Differentiated approaches to correcting the condition of the ocular surface in dry eye syndrome: a literature review. Russian Journal of Clinical Ophthalmology. 2025;25(2):109–116 (in Russ.). DOI: 10.32364/2311-7729-2025-25-2-5

Dry eye disease (DED) is a clinically significant multifactorial disorder of the ocular surface and tear film as it results in ocular discomfort and visual impairment and predisposes the cornea to infections. It is important for the quality of life and tends to be a chronic disease. It is also common, as the prevalence is estimated between 5 % to 30 % and this increases with age. Therefore, it is recognised as a growing public health problem that requires correct diagnosis and appropriate treatment. There are two main categories of DED: the deficiency of tear production (hyposecretive), which includes Sjögren syndrome, idiopathic or secondary to connective tissue diseases (e.g. rheumatoid arthritis), and non-Sjögren syndrome (e.g. age-related); and the tear evaporation category, where tears evaporate from the ocular surface too rapidly due to intrinsic causes (e.g. meibomian gland disease or eyelid aperture disorders) or extrinsic causes (e.g. vitamin A deficiency, contact lenses wear, ocular allergies). Management of the disease aims to enhance the corneal healing and reduce patient’s discomfort. This is based on improving the balance of tear production and evaporation by increasing the tear film volume (lubrication drops) and improving quality of tear film (ex omega-3 supplements, lid hygiene, tetracyclines), reducing the tear film evaporation (paraffin ointments, therapeutic contact lenses), reducing tear’s drainage (punctal plugs, cautery) and finally by settling down the ocular surface inflammation (steroids, cyclosporine, autologous serous), as appropriate. In this article we will review the clinical presentation, differential diagnosis and treatment options for DED.

Dry Eye Disease: The Clinician’s Guide to Diagnosis and Treatment Penny A. Asbell and Michael A. Lemp, New York, Thieme; 2006. $139.95. Two of the most well known names in the field of dry eye disease have put together this remarkable book on the diagnosis and treatment of one of the most common diseases encountered in caring for patients and their eyes. It is a slim volume at just over 200 pages and consequently not too onerous to pick up and carry around. Within these 200 pages are eighteen chapters, each penned by a group of one to three experts who have helped contribute to our contemporary understanding of this complex disease. Each chapter begins with a bulleted listing of “key points” to help the reader quickly focus in on the most salient issues. The chapters are subdivided into meaningful sections that assist in finding the desired information. And there is a wealth of information reviewed in each chapter. The information is enhanced by the inclusion of numerous tables and figures, with some chapters including several descriptive color photographs. Its organization generally allows the reader rapid access to information on the performance of clinical diagnostic tests and treatment options, in both cases covering the old standbys as well as more novel approaches. It discusses dry eye disease in the context of lid disease, contact lens wear, refractive surgery, and systemic disease. Overall it is an excellent resource for students and seasoned clinicians that provides a thorough review of current understandings of dry eye disease diagnosis and treatment options through the eyes of some highly respected experts. The book begins with a two chapters reviewing the epidemiology of dry eye disease and its pathogenesis. The next three chapters are devoted to the diagnosis of dry eye using questionnaires, in-office diagnostic tests, and an interesting summary of a number of potentially useful newer tests that have yet to find their way into most clinics. You will then find a chapter on the diagnosis and management of meibomian gland disease and following that, four chapters on treatments for dry eye disease covering tear replacement strategies, modulation of inflammation and immunity, complementary and alternative medicine approaches, and mucin stimulation and hormonal treatments. The next chapters are devoted to dry eye disease in the context of contact lens wear and refractive surgery, the diagnosis and treatment of severe dry eye disease, and a description of surgical approaches including the use of punctal plugs as well as more invasive approaches that are used in the management of severe lid and ocular surface disorders. A chapter on dry eye in the context of systemic issues provides a fairly detailed guide to Sjogren’s Syndrome and aqueous deficient dry eye, and brief discussions of sex hormones, graft-versus-host disease, Stevens-Johnson syndrome, and pseudo-pemphigoid. The final three chapters are aimed at passing along lessons learned from clinical trials in dry eye disease, keeping current on medical information and drug development for dry eye disease, and providing a peek at what the future might hold. The book is far more detailed than a straightforward clinical “guide” and accordingly I think it will find its use more in the context of a usefully thorough and informed reference on dry eye disease from its milder forms through its most severe. It is not a simple step-by-step guide to take you from the moment the dry eye patient sits down in your chair to when they leave your office with a diagnosis and treatment plan. That is not to say that such information is not in the book. It is. For example, Chapter 4 contains not only fairly in-depth descriptions of the most commonly used diagnostic tests including pictorial descriptions of surface staining grading systems, but also a recommended ordering for the conduct of such tests for a routine dry eye examination. It might have been nice to have some of the most clinically useful information also available on little note-sized cards to pull out and tack up on the wall for easy reference on the fly. Nevertheless, having such a thorough discussion of dry eye and all of its nuances together in one tidy volume should help any clinician who manages patients with dry eye disease. A little disappointing to me is the timing of the book’s release at just about the same moment as the publication of the full report of the International Dry Eye Workshop (DEWS; Ocular Surface, 2007). Thus, readers will not find the newest definition of dry eye disease and some other information that became available with the publication of the DEWS report. This is a common issue affecting books in general, but there are advantages to the book too. Whereas the DEWS report represents a consensus view derived from the efforts of a large group of international experts, here each author has had more leeway to emphasize his/her own point of view. The book does a nice job of emphasizing the evolution in our understanding of dry eye disease, its complexity, and its importance to our patients. It is written for the clinician by clinicians, but ultimately, I hope that our patients would be the biggest beneficiaries of the book as more clinicians gain a broader and more evidence-based understanding of how to diagnose and effectively manage this very common and troubling eye disease. Debra A. Schaumberg Brigham and Women’s Hospital Harvard Medical School Boston MassachusettsFigure

INTRODUCTION: The term Dry eye can be attributed to the Swedish ophthalmologist Henrik S.C. Sjogren. He was the first to refer to the triad of dry eye, dry mouth, and joint pain in his original thesis in 1933 Zur kenntnis der keratoconjuctivitis sicca. Dry eye disease is a “multifactorial disease of the tears and ocular surface that results in discomfort, visual disturbance, and tear film instability resulting in damage to the ocular surface. Dry eye disease is also accompanied by increase in osmolarity of the tear film and inflammation of the ocular surface” [i] The ocular surface (cornea, conjunctiva, accessory lacrimal glands), meibomian glands (specific sebaceous glands of the eyelid margin, which produce the outer lipid film of the tear film), the main lacrimal gland, and the innervation between them form a functional unit. Any or all of these structures may be affected in dry eye disease Recent studies show that dry eye is an inflammatory disease that has many features in common with autoimmune disease Stress to the ocular surface (environmental factors, infection, endogenous stress, antigens, genetic factors) is considered as the main triggering mechanism. Proinflammatory cytokines, chemokines, and matrix metalloproteinases lead to the expansion of autoreactive T helper cells which infiltrate the ocular surface and lacrimal gland which results in damage to the ocular surface.Classification into “dry eye with reduced tear production (aqueous-deficient)” and “dry eye with increased evaporation of the tear film (hyperevaporative)” has proved useful on practical grounds.From different studies it is assumed that around 10% of patients with dry eye have aqueous-deficient disorder AND Hyperevaporative disorders is mostly caused by dysfunction of the meibomian glands..Mixed hyperevaporative/aqueous-deficient accounts for more than 80% of the total cases.[ii] The prevalence of dry eye in the world population ranges from 6 to 34 %. It is more common in those aged over 50, and affects mainly women. Since the introduction of the Schirmer’s test in 1903, other tests have been developed to evaluate dry eye, such as biomicroscopy, the tear film breakup time (BUT), vital dyes (lissamine green and rose bengal), fluorescein, leaf fern test, corneal sensitivity test, conjunctiva impression cytology, optical coherence tomography (OCT), and tear osmolarity measurement. There is no gold standard diagnostic test but it is recommended to combine at least two tests. Strategies for treating Dry Eye Disease have recently been modified and include patient education, tear substitute, corticosteroids, secretagogues, fatty acids, immunomodulators, occlusion of lacrimal puncta surgery and, tarsorrhaphy. Biological therapy and new topical immunomodulators such as tacrolimus, tofacitinib and IL-1 receptor inhibitor are being tested.[iii] [i] Brewitt H, Sistani F. Dry eye disease: the scale of the problem. Survey of ophthalmology. 200 Mar 11;45:S199-202. [ii] Messmer EM. The pathophysiology, diagnosis, and treatment of dry eye disease. Deutsches Ärzteblatt International. 2015 Jan;112(5):71. [iii] Valim V, Trevisani VF, de Sousa JM, Vilela VS, Belfort R. Current approach to dry eye disease. Clinical reviews in allergy & immunology. 2015 Dec;49(3):288-97.

Dry eye disease (DED) is a chronic ocular surface condition that affects millions of people and has a worldwide prevalence of over 50%. Morbidities associated with DED include pain, discomfort, and blurring of vision. DED has evolved into a pressing public health concern due to the economic and psychosocial burden it imparts on affected individuals. A multitude of etiological or risk factors has been identified, ranging from aging, surgery, and malnutrition to occupational environment. These factors contribute to ocular surface inflammation, epitheliopathy, hyperosmolarity, tear film instability, and neurosensory abnormalities that culminate in the presentation of signs and symptoms of DED. Aberrant and chronic ocular surface inflammation emerged as a key modifiable contributor in DED pathobiology due to its direct association with signs and symptoms of DED, and resolution of disease following the use of anti-inflammatory agents. Despite being one of the most successful therapeutic strategies in DED management, there is a substantial number of patients who are refractory to anti-inflammatory regimen and other current forms of treatment. In addition, complexity in the management of DED increases with the presence of discordance between signs and symptoms in some patients. Hence, there is an urgent and constant need to identify additional disease mechanisms and contributors that can be targeted to resolve the morbidities associated with DED. The current special issue DED is designed to report and highlight the various translational investigations that have been directed towards improving DED management in clinical practice. These include (i) disease-specific and biomarker-based stratification of patients for personalized treatment and prevention of disease progression; (ii) newer therapeutic strategies that include both pharmacological and non-pharmacological (such as thermal pulsation therapy) approaches; (iii) novel molecular factors and mechanisms including novel proteins, interferon imbalance and ionic imbalances; (iv) physiological variations, such as hormonal and nutritional changes; (iv) newer disease models, including animal models that can be used to understand newer mechanisms and to test emerging and novel therapeutic agents. In summary, the contributors to this special issue have provided critical additions to the DED knowledgebase, with reference to both pathological mechanisms and clinical management. About the AuthorDr. Rohit Shetty Dr. Rohit Shetty is the Vice Chairman of Narayana Nethralaya, Bangalore, a cornea-refractive surgeon and a clinician scientist with a keen interest in keratoconus, corneal ectatic disorders and dry eye disease. He has been practicing high volume refractive surgery for 15 years now. Dr Shetty obtained his FRCS Glasgow in 2006 and is currently an FRCS examiner. He is the Chief Mentor for the Dual Academic Program (PhD & Clinical Fellowship) at Narayana Nethralaya Eye Institute, Bangalore and Maastricht University. He was recently awarded the Fellowship of the American College of Surgeons. Dr Shetty has close to 350 publications in peer-reviewed journals and is a reviewer for many indexed journals in the specialty. He is also on the editorial board of the Journal of Refractive Surgery. With a keen interest in imaging, some of his research includes, waveform analysis of deformation and deflection amplitude in keratoconus, influence of ocular spherical aberration on near and intermediate visual acuity in presbyopic eyes, biomechanics of LASIK Flap and SMILE Cap and corneal tomography in post-refractive surgery ectasia. In the 2015 annual conference of the All India Ophthalmological Society, Dr Shetty won the prestigious Col. Rangachari Award for his work on "Is Inflammation Driving Keratoconus? A Holistic Study of Molecular Pathways". The American Academy of Ophthalmology recently conferred the Achievement Award to Dr Rohit Shetty for distinguished services rendered over the years to the programs of the society. Besides being conferred the Casebeer Award for outstanding contribution to refractive surgery, he was recently awarded the Achievement Award by the Asia-Pacific Academy of Ophthalmology.

Homeostasis of the lacrimal functional unit is needed to ensure a well-regulated ocular immune response comprising innate and adaptive phases. When the ocular immune system is excessively stimulated and/or immunoregulatory mechanisms are disrupted, the balance between innate and adaptive phases is dysregulated and chronic ocular surface inflammation can result, leading to chronic dry eye disease (DED). According to the Tear Film and Ocular Surface Society Dry Eye Workshop II definition, DED is a multifactorial disorder of the ocular surface characterized by impairment and loss of tear homeostasis (hyperosmolarity), ocular discomfort or pain, and neurosensory abnormalities. Dysregulated ocular immune responses result in ocular surface damage, which is a further contributing factor to DED pathology. Several therapeutics are available to break the vicious circle of DED and prevent chronic disease and progression, including immunosuppressive agents (steroids) and immunomodulators (cyclosporine and lifitegrast). Given the chronic inflammatory nature of DED, each of these agents is commonly used in clinical practice. In this study, we review the immunopathology of DED and the molecular and cellular actions of current topical DED therapeutics to inform clinical decision making.