�ʹڲ�Ʊ

Research title:��The ocular surface innate and adaptive immune response in dry eye disease

Supervisors:��Scientia Professor Fiona Stapleton, Professor Isabelle Jalbert, Associate Professor Blanka Golebiowski

��

Abstract

The immune system plays a significant role in the pathogenesis of dry eye disease (DED) by modulating ocular surface inflammation. Inflammation is evidenced by elevated tear cytokines and chemokines, and by the activation of pro-inflammatory cells such as dendritic cells and lymphocytes. A systematic review and meta-analysis of in vivo confocal microscopy (IVCM) studies was conducted and showed significantly higher central corneal epithelial immune cell (EIC) density in both Sjögren disease associated DED (SjD-DED) and non-Sjögren disease DED (nSjD-DED) compared to healthy controls. Subgroup analysis revealed that SjD-DED exhibited significantly greater central corneal immune activity than nSjD-DED. However, data on EIC distribution across other corneal locations in DED remain limited. To address this gap, a cross-sectional study was conducted to assess the topographical distribution, diurnal variation, and day-to-day repeatability of EIC density and morphology in DED. No significant diurnal variation was observed in EIC density or morphology. However, corneal location had a significant effect on EIC density: it was highest at the inferior cornea (mean: 99.5 ± 50.04 cells/mm²) and temporal limbus (100.5 ± 32.7 cells/mm²), and lowest at the central cornea (45.6 ± 41.0 cells/mm²) (all p < 0.001). Larger and dendriform EICs were more frequently observed in the conjunctiva, inferior, and temporal cornea than in the central cornea (all p ≤ 0.007). Day-to-day repeatability was lower in the central and temporal cornea than in other locations (CoR: ±23.8–47.9 cells/mm²). These findings highlight the presence of location-specific immune activity, suggesting that imaging sites beyond the central cornea should be considered. The absence of diurnal variation supports the potential of EICs as reliable biomarkers for DED diagnosis and treatment monitoring. Functional IVCM (Fun-IVCM), a novel dynamic imaging technique, enables real-time assessment of corneal immune cell behavior. Time-lapse videos allow differentiation of corneal EIC subtypes: T cells (highly motile, small), dendritic cells (larger, with dendrites, less motile), and anterior stromal macrophages. Additionally, conjunctival immune profiling using impression cytology and flow cytometry allows phenotyping of immune cell populations (CD45, CD3, CD4, CD8, CD11c, HLA-DR). While topical ciclosporin A (CsA) is an established treatment for DED, however, its direct effects on ocular immune responses and tear cytokines have not been systematically investigated. A randomized controlled clinical trial is currently underway to compare the effects of 0.1% CsA+ its vehicle versus its vehicle alone over 12 weeks on ocular immune responses, utilizing Fun-IVCM, flow cytometry, and multiplex cytokine assays (IL-2, IL-4, IL-6, IL-12, IL-17, IL-23, IFN-γ).

��

Biography

Soumen Sadhu is an optometrist and clinical researcher specializing in ocular surface immunobiology and the development of targeted anti-inflammatory therapies for dry eye disease (DED). As an early-career researcher, he has established a strong academic profile with 12 peer-reviewed publications (including six as first author), accumulating 151 citations, an H-index of 4 (Google Scholar, March 2025), and a Field-Weighted Citation Impact (FWCI) of 1.9 (Scopus, March 2025).

In 2021, he became one of the youngest researchers from India to be elected as a Fellow of the American Academy of Optometry (FAAO). His PhD is supported by the University International Postgraduate Award, one of Australia’s most competitive scholarships for international doctoral students.

Soumen has been awarded distinction in the Foundations of University Learning and Teaching (FULT) program and holds AdvanceHE certification, demonstrating his commitment to excellence in teaching and professional development. He has presented his research at 11 international conferences and has received five international awards, including the prestigious 2025 Rod Tahran Ezell Fellowship from the American Academy of Optometry.

He aspires to become a clinical scientist, contributing meaningful advancements to ocular immunology and inflammation research. His research focuses on immunomodulatory drug development, immune cell profiling in DED, and the identification of novel immune biomarkers for treatment monitoring. He believes this work will benefit patients with refractory and treatment-resistant inflammatory dry eye disease.

��

Education

2023- Present - Ph.D. student in Optometry at University of New South Wales, Australia

2018-2021- Master of Optometry from The Tamil Nadu Dr. MGR Medical University, Sankara Nethralaya, Chennai, India

2012- 2016 – Bachelor’s in optometry from West Bengal University of Technology, NSHM Knowledge Campus, India

��

Awards

2025 - Rod Tahran Ezell Fellowship (EssilorLuxottica) recipient, American Academy of Optometry

2025 - Australian and New Zealand society of immunology International travel Award

2025 - �ʹڲ�Ʊ Development and Research Training Grant

2024- Australian and New Zealand society of immunology travel bursary Award

2024- American Academy of Optometry Foundation & Cooper Vision Student Travel Fellowship Award

2024- �ʹڲ�Ʊ Development and Research Training Grant

2023 - Scholarship, University International Postgraduate Award to study Ph.D. �ʹڲ�Ʊ, Australia

2022 - Best Oral Presentation Award - India Vision Institute Optometry Conference, India

2021 - Best Ocular Scientific Photography Award- Dr. Rajeswari Mahadevan memorial scientific session

��

Memberships and Affiliations

2024 – present Member, The Association for Research in Vision and Ophthalmology (ARVO)

2024 – present Member, Australian and New Zealand Society of Immunology

2023 – present Member, Cornea and Contact Lens Society of Australia

2021 – present Member, American Academy of Optometry

2020 – present Member, Tear Film and Ocular Surface Society

2018 – present Member, Sankara Nethralaya Alumni

2018 – present Member, Indian Eye Research Group & Association of Research and Vision Ophthalmology

��