Ocular Surface Center

A standard approach to the diagnosis of dry eye disease across eye care practitioners is critical to reassuring the patient, providing consistency between practitioners and informing governments as to the true prevalence and resulting healthcare needs. The Tear Film & Ocular Surface Society (TFOS) Dry Eye Workshop (DEWS) III has reviewed the evidence-base since their previous reports published in 2017 and revised the definition to "Dry eye is a multifactorial, symptomatic disease characterized by a loss of homeostasis of the tear film and/or ocular surface, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities are etiological factors." Key features from the definition include that dry eye disease is multifactorial, is a disease and not a syndrome and is always symptomatic. Differential diagnosis and ocular examination guidance is given along with the risk factors that should be discussed with the patient. The recommended screening questionnaire is the OSDI-6 with a cut-off score ≥4. A positive result together with a non-invasive breakup time <10s or alternatively tear film hyperosmolarity (≥308mOsm/L in either eye or an interocular difference >8mOsm/L) or alternatively >5 corneal fluorescein and/or >9 conjunctival lissamine green punctate spots and/or lid margin lissamine green staining of ≥2mm length & ≥25 % width, gives a diagnosis of dry eye. Subclassification was separated into tear film deficiencies (lipid, aqueous and mucin/glycocalyx), eyelid anomalies (blink/lid closure and lid margin) and ocular surface abnormalities (anatomical misalignment, neural dysfunction, ocular surface cell damage/disruption and primary inflammation/oxidative stress) components, with appropriate clinical tests and cut-offs provided to identify these etiological drivers in an individual, to inform appropriate management and therapy.

ABSTRACT Background Ocular surface disorders (OSD) and glaucoma often co exist. Intraocular pressure lowering medications and preservatives used with them may lead to ocular surface toxicity and drug induced cicatrizing conjunctivitis (DICC). Surgical management of glaucoma helps in reducing the requirement of topical anti glaucoma drugs but, at the same time, may also disrupt the ocular surface. On the other hand, medical therapies and surgeries required for management of OSD often lead to secondary glaucoma, thereby inducing a vicious cycle. Methods Relevant articles (English only) up to January, 2025 were searched from PubMed and summarized. Results Our review discusses the epidemiology, various diagnostic, therapeutic and surgical aspects of this interlinked scenario in a comprehensive manner. Medical therapies (steroids) utilized for controlling inflammation in OSD and related steroid induced glaucoma, anti glaucoma medications (and their preservatives) causing OSD and their respective available alternatives have been discussed in individual sections. Similarly, glaucoma surgeries causing OSD, surgeries for OSD leading to secondary glaucoma and the surgical considerations with possible alternatives, including the novel therapies, have been reviewed. The future directions, along with the role of gut microbiome in ocular diseases and the various therapeutic agents/interventions under clinical investigations, are also explored. Conclusion A deeper understanding of the interplay of different factors in these co-morbid conditions will help in breaking the vicious cycle induced and therefore, in offering more effective treatment. Recommendations for clinicians have been suggested to help optimize the treatment provided to this specific patient cohort of ‘OSD and glaucoma’.

Aging is a risk factor for dry eye. We sought to identify changes in the aged mouse corneal epithelial transcriptome and determine how age affects corneal sensitivity, re-epithelialization, and barrier reformation after corneal debridement. Corneal epithelium of female C57BL/6J (B6) mice of different ages (2, 12, 18, and 24months) was collected, RNA extracted, and bulk RNA sequencing performed. Cornea sensitivity was measured with an esthesiometer in 2- to 3-month-old, 12- to 13-month-old, 18- to 19-month-old, and 22- to 25-month-old female and male mice. The 2-month-old and 18-month-old female and male mice underwent unilateral corneal debridement using a blunt blade. Wound size and fluorescein staining were visualized and photographed at different time points, and a re-epithelialization rate curve was calculated. There were 157 differentially expressed genes in aged mice compared with young mice. Several pathways downregulated with age control cell migration, proteoglycan synthesis, and collagen trimerization, assembly, biosynthesis, and degradation. Male mice had decreased corneal sensitivity compared with female mice at 12 and 24 months of age. Aged mice, irrespective of sex, had delayed corneal re-epithelialization in the first 48 hours and worse corneal fluorescein staining intensity at day 14 than young mice. Aged corneal epithelium has an altered transcriptome. Aged mice regardless of sex heal more slowly and displayed more signs of corneal epithelial defects after wounding than young mice. These results indicate that aging significantly alters the corneal epithelium and its ability to coordinate healing.

The purpose of this study was to determine if there are significant differences in the concentrations of tear proteins in Sjögren's syndrome keratoconjunctivitis sicca (SS KCS) compared to healthy controls. Tear samples were collected with unmarked Schirmer strips from 15 patients with SS KCS and 21 healthy controls. Tear protein was eluted and the concentration measured. Inflammatory mediators were assayed with a Raybiotech L-507 glass slide array and normalized by strip wetting length. All patients underwent an ocular surface exam to evaluate tear break-up time (TBUT), corneal fluorescein (CF) staining, and conjunctival (CJ) staining. The symptom assessment questionnaire in dry eye (SANDE) scores were collected for all patients. Two hundred fifty-three of the 507 tear proteins analyzed were significantly different in patients with SS compared to controls. Two hundred forty-one if the proteins were upregulated and 12 were downregulated. One hundred eighty-one differentially expressed proteins were significantly correlated with all four clinical parameters: TBUT, CF staining, CJ staining, and SANDE score. These findings indicate that hundreds of factors can be assayed in tear proteins collected from a Schirmer strip. The results suggest tear protein concentrations are altered in patients with SS KCS compared to controls. The upregulated tear proteins correlated with clinical measures of dry eye symptoms and disease severity. Tear proteins could serve as important biomarkers for studying pathogenesis and in clinical diagnosis and management of SS KCS.

Aging is associated with inflammation and oxidative stress in the lacrimal gland (LG). We investigated if heterochronic parabiosis of mice could modulate age-related LG alterations. In both males and females, there were significant increases in total immune infiltration in isochronic aged LGs compared to that in isochronic young LGs. Male heterochronic young LGs were significantly more infiltrated compared to male isochronic young LGs. While both females and males had significant increases in inflammatory and B-cell-related transcripts in isochronic and heterochronic aged LGs compared to levels isochronic and heterochronic young LGs, females had a greater fold expression of some of these transcripts than males. Through flow cytometry, specific subsets of B cells were increased in the male heterochronic aged LGs compared to those in male isochronic aged LGs. Our results indicate that serum soluble factors from young mice were not enough to reverse inflammation and infiltrating immune cells in aged tissues and that there were specific sex-related differences in parabiosis treatment. This suggests that age-related changes in the LG microenvironment/architecture participate in perpetuating inflammation, which is not reversible by exposure to youthful systemic factors. In contrast, male young heterochronic LGs were significantly worse than their isochronic counterparts, suggesting that aged soluble factors can enhance inflammation in the young host. Therapies that aim at improving cellular health may have a stronger impact on improving inflammation and cellular inflammation in LGs than parabiosis.