Endothelial Implant (EndoArt): A Potential Alternative to Endothelial Keratoplasty
Sunita Chaurasia, MD - LV Prasad Eye Institute
Discussion 11:20 AM
Endo-TekTM: A Novel Endothelial Cell Therapy Using a Vitrigel Carrier
11:25 AM
Albert Jun, MD, PhD - University of Virginia School of Medicine
Discussion 11:35 AM
Prevention and Management of Post-Keratoplasty Infections
11:40 AM
Bennie Jeng, MD - University of Pennsylvania Perelman School of Medicine
Discussion 11:50 AM
Donor Corneas for Transplantation: An Evidence-Based Approach
11:55 AM
Jennifer Li, MD - University of California, Davis
Discussion 12:05 PM
PANEL 2 - INNOVATION AND NEW TECHNOLOGIES
12:10 PM
Pictured left to right:
Moderators: Sadeer B. Hannush, MD /Martine Jager, MD, PhD
Kathryn Colby, MD, PhD - NYU Grossman School of Medicine
Giulio Ferrari, MD, PhD - Ospedale San Raffaele, Milan
Enrique Graue-Hernández, MD, MSc - Universidad Nacional Autonoma de México
Viridiana Kocaba, MD, PhD - Singapore Eye Research Institute
Shigeto Shimmura, MD, PhD - Fujita Medical Innovation Center Tokyo
LUNCH 12:50-2:15 PM
SESSION 6 - INNOVATION
Moderator: Joseph Ciolino, MD
2:15 PM
Corneal Stromal Regeneration: Stem Cells, Hydrogels, & 3D Bioprinting
Sayan Basu, MD, PhD - LV Prasad Eye Institute
Discussion 2:25 PM
2:30 PM
Novel Translational Investigations in Management of Corneal & Ocular Surface Immune Disorders
Reza Dana, MD, MSc, MPH - Harvard Medical School
Discussion 2:40 PM
Repurposing Insulin for the Ocular Surface
2:45 PM
Silke Oellerich, PhD - University Hospital Brussels
Discussion 2:55 PM
PROGRAM - Saturday, October 5, 2024 (Continued)
SESSION 6 - INNOVATION (Continued)
3:00 PM
AI in Keratoplasty
Pravin Vaddavalli, MD, PhD - LV Prasad Eye Institute
Discussion 3:10 PM
Novel Lymphangioregressive Pretreatment of High-Risk Corneas to Promote Graft
3:15 PM
Survival: Preclinical and Early Clinical Evidence
Claus Cursiefen, MD, PhD - University Hospital of Cologne
Discussion 3:25 PM
3:30-3:50 PM
3:50 PM
4:00 PM
4:50 PM
Introduction to Claes H. Dohlman Lecture
Ula Jurkunas, MD - Harvard Medical School
CLAES H. DOHLMAN LECTURE
The Innervation of the Cornea: Molecular and Cellular Basis of Sensation, Plasticity and Trophism
Carlos Belmonte, MD, PhD - Universidad Miguel Hernández-CSIC
Closing Remarks and Poster Winners and Travel Award Announcement
Ula Jurkunas, MD - Harvard Medical School
GROUP PHOTO 5:00-5:10 PM
8:00-10:00 PM
DINNER AT CASA DO ALENTEJO (R. das Portas de Santo Antão 58, 1150-268)
POSTER SESSION
To access the online program with poster abstracts, scan the QR code or visit: bit.ly/3BcRDfU
#) AUTHOR - TITLE
1) Anna Agas-Lange - Various Types of Endothelial Corneal Dystrophy in Confocal Microscopy
2) Dennis Akrobetu - Pediatric Corneal Scarring: Etiologies and Visual Burden
3) Shazia Ashraf - Modulation of ATM Enhances DNA Repair in G2/M Phase of Cell Cycle and Averts Senescence in Fuchs Endothelial Corneal Dystrophy
4) Shreya Bhatt - Investigating Visual Photosensitivity and Dry Eye Symptoms in Individuals With Traumatic Brain Injuries
5) Raluca Bievel-Radulescu - A New Resource for Eye Banks: Post- SMILE Stromal Corneal Lenticules
6) Nikolay Boychev - Sociodemographic Risks Associated With Acute Corneal Hydrops
7) Enchi Chang - Outcomes of Using the Biovance® 3L Ocular Human Amniotic Membrane Allograft for Corneal Epithelial Defects
8) Se Hyun Choi - Development of a Comprehensive Dry Eye Management App: Key Insights From Patient and Ophthalmologist Surveys in South Korea
9) In Young Chung - Structural and Functional Characteristics of Glaucoma in Patients With Boston Keratoprosthesis Type 1
10) Neha Deshpande - Transcriptome Analyses of Human Corneal Endothelial Cell Lines Derived From Patients With Fuchs Endothelial Corneal Dystrophy
POSTER SESSION (Continued)
#) AUTHOR - TITLE
11) Hongyu Duan - Novel Cytokine CSBF: An Endogenous Regulator of Inflammation in Dry Eye Disease and its Therapeutic Potential
12) Eileen (Yilin) Feng - Minimizing Eye Drop Burden After Cataract Surgery in Patients With Retinitis Pigmentosa
13) Dominique Geoffrion - Inflammatory Tear Cytokine Levels in Patients With Boston Keratoprosthesis Type 1 Versus Primary Angle Closure Glaucoma
14) Andrew Griswold - Spatial Regulation of the NLRP1 Inflammasome in the Cornea
15) Oylum Buse Gur - Evaluation of Temperature Changes on the Ocular Surface After Intravitreal Injection Using a Thermal Camera
16) Helen Gutiérrez - Refining Cell Culture of Corneal Epithelial Cells Obtained After Advanced Surface Ablation
17) Ema Karakoleva - PTSD is Associated With Increased Activation of Photophobia Brain Circuits in Individuals With Chronic Ocular Pain
18) Agnieszka Kuligowska - Modern Diagnostic and Treatment Strategies for Avellino Dystrophy – A Case Study
19) Hayoung Lee - Therapeutic Effects of Decellularized Extracellular Matrix-Based Adhesive Restorative Material on the Corneal Regeneration in a Model of Corneal Alkali Burn
20) Jie Liu - Minimally Invasive Keratoprosthesis (mi-KPro) for Vision Restoration After Severe Chemical Injury
21) Mert Mestanoglu - Fibrillar Layer Positive Fuchs Endothelial Corneal Dystrophy Eyes Demonstrate Tomographic Features of Corneal Edema
22) In Hee Moon - Analysis of Tear Proteome and Clinical Correlations in Patients With Dry Eye Disease
23) Guillaume Mullie - Comparison of Outcomes Between the Ahmed Glaucoma Valve and the Baerveldt Glaucoma Implant in Eyes With Boston Keratoprosthesis
24) Mustafa Kemal Özaslan - The Influence of Different Eye-Rubbing Techniques on Corneal and Anterior Segment Morphology: A Comparative Analysis of Knuckle, Fingertip, and Fingernail Methods
25) Calin Pater - A Double-Masked, Randomized, Placebo-Controlled, Parallel-Group, 12-Week, Phase 2 Study to Investigate the Safety and Efficacy of Ripasudil (K-321) Eye Drops After Descemetorhexis in Patients With Fuchs Endothelial Corneal Dystrophy
26) Hong Qi - CMTM3 Plays a Pathogenic Role in Dry Eye Disease
27) Alberto Recchioni - Swept-source Optical Coherence Tomography in Ocular Surface Diseases: Repeatability and Limits of Anterior Segment Analysis
28) Chhavi Saini - T Cell Cytokine Profiles in Subjects With Boston Keratoprosthesis
29) Chloe Shields - Acute Impact of Transcutaneous Electrical Nerve Stimulation on Ocular Pain
30) Hueyjong Shih - Case Report of use of Compounded Losartan Drops to Minimize Corneal Scarring After a Full Thickness Corneal Laceration
31) Shweta Suiwal - Ritanserin and Duloxetine as Treatment Options for Aniridia Associated Keratopathy (AAK) – Gene Expression Study in Primary Limbal Epithelial Cells, In Vitro
32) Rachel Tandias - Concurrent Limbal Stem Cell Deficiency and Neurotrophic Keratopathy in Graft-Versus-Host Disease
33) Bernd Vanmeerhaeghe - Corneal Endothelial Cell Transfection by Photoporation of a Photosensitizer Loaded Hyaluronic Acid Gel
34) Joanna Wasielica-Poslednik - Management of Postoperative Intraocular Pressure Elevation After DMEK
35) Qingguo Xu - Nanomedicine Strategy for Treating High Risk Corneal Transplantation Rejection
36) Gink Yang - Can FGF7 be a Therapeutic Target for Fuchs Endothelial Corneal Dystrophy?
37) Leyla Yavuz Saricay - 1-Year Changes in the Central Cornea on Anterior Segment OCT and In Vivo Confocal Microscopy in Eyes With Limbal Stem Cell Deficiency Receiving Cultivated Autologous Limbal Epithelial Cell (CALEC) Transplantation
38) Haozhe Yu - Tear Lipid Peroxidation Products as new Potential Biomarkers for Dry Eye Disease Diagnosis
39) Sarah Zwingelberg - The Influence of Obesity, Diabetes Mellitus and Smoking on Fuchs Endothelial Corneal Dystrophy (FECD)
Silver Level
Bronze Level
Contributor Level
Funding for this conference was made possible (in part) by 1R13EY036277-01A1 from the National Eye Institute. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention by trade names, commercial practices, or organizations imply endorsement by the U.S. Government.
Candidate: Anna Agas-Lange
Poster #: 1
Various Types of Endothelial Corneal Dystrophy in Confocal Microscopy
Anna Agaś-Lange, Martyna Nocoń-Bratek, Adrian Smędowski
Purpose: To investigate the characteristics of endothelial corneal dystrophies and their impact on the progression of the local condition.
Methods: All patients were examined by slit-lamp biomicroscopy followed by evaluation using in vivo confocal microscopy (HRT III, RCM, Heidelberg, Germany), focusing on the corneal endothelium and Descemet’s membrane.
Results: In confocal microscopy examination, precise visualization of characteristic features of endothelial corneal dystrophy is attainable. Posterior Corneal Dystrophies include Fuchs endothelial corneal dystrophy (FECD), posterior polymorphous corneal dystrophy (PPCD), congenital hereditary endothelial corneal dystrophy (CHED) and X- linked endothelial corneal dystrophy (XECD). By evaluating reduced endothelial cell count, pleomorphism in size and shape of endothelial cells and thickening of Descemet’s m embrane we are able to estimate the risk of developing corneal edema in the future. It helps in predicting the future necessity of a corneal transplant and allows for the detection of patients susceptible to corneal complications from other ophthalmic procedures such as cataract surgery.
Conclusions: The presented data demonstrate that in vivo confocal microscopy complements slit-lamp examination for assessing patients suspected of corneal dystrophies. Confocal microscopy allows for the precise visualization of even the smallest abnormalities, which may go unnoticed in standard ophthalmic examinations. This method enables the detection of early signs of intracorneal changes and the assessment of their scope and severity. As a result, it allows for the formulation of a precise therapeutic plan. The acquired confocal images constitute valuable elements for further monitoring of the disease progression.
Candidate: Dennis Akrobetu
Poster #: 2
Pediatric Corneal Scarring: Etiologies and Visual Burden
Dennis Akrobetu, Leyla Yavuz Saricay, Asmaa A. Zidan, Rachel Tandias, Euna Lee, Gena Heidary, David G. Hunter, Thomas H. Dohlman
Purpose: Corneal scarring is one of the most common ophthalmic conditions leading to visual deficit worldwide. Despite this, relatively little is known about the prevalence and impact of corneal scarring in the pediatric population (patients < 18 years of age) in the United States. Given the risk of amblyopia, it is important to clarify the causes and visual outcomes of pediatric corneal scarring. In this study, we investigated the demographics, etiologies, and visual burden for pediatric patients seen through the Mass. Eye and Ear Cornea Service and the Boston Children’s Hospital Pediatric Ophthalmology Service with a diagnosis of corneal scar over a 15-year period (July, 2007, to June, 2022).
Methods: For this retrospective study, patients meeting inclusion criteria were found via Hound Dog word search within the electronic medical record system, with subsequent manual review of clinical notes to identify those with a diagnosis of corneal scarring and/or corneal opacity.
Results: In total, 325 patients were included in our analysis. Fifty-nine percent were male; the median age was 7.0 years with an interquartile range of 4.0 and 9.0 years. The median best corrected visual acuity (BCVA) at time of diagnosis was 0.30 (logMAR). Most corneal scars were unilateral (94%). Overall, the most common etiology for scarring was trauma (29%). Congenital disease was most likely to lead to visually significant outcomes, while non-infectious keratitis was least likely to lead to visually significant outcomes. Corneal degeneration was associated with the poorest average BCVA (logMAR 3.0) and non-infectious keratitis was associated with the best average BCVA (logMAR 0.10).
Conclusions: There are diverse etiologies for corneal scarring in the pediatric population. Each etiology is associated with varying visual outcomes, with corneal degeneration being associated with the poorest BCVA and noninfectious keratitis being associated with the best BCVA.
Candidate: Shazia Ashraf
Poster #: 3
Modulation of ATM Enhances DNA Repair in G2/M Phase of Cell Cycle and Averts Senescence in Fuchs Endothelial Corneal Dystrophy
Shazia Ashraf, Neha Deshpande, Ula Jurkunas
Purpose: Fuchs endothelial corneal dystrophy (FECD) is an age-related disorder leading to accelerated loss of corneal endothelial cells (CEnCs). We have previously shown that ultraviolet-A (UVA) light causes DNA damage and leads to FECD phenotype in a non-genetic mouse model. Here, we investigate the mechanism of Ataxia Telangiectasia Mutated (ATM) mediated DDR activation under acute and chronic oxidative stress induced by UVA and catechol estrogen 4-OHE2 exposure.
Methods: NQO1+/+ and NQO1-/- cell lines were treated with UVA and 4-OHE2 +/-ATM inhibitor (ATMi), followed by recovery for 1 and 24 h for acute, and 5 days for chronic stress. Levels of pATM, DNA damage marker γH2AX and cell-cycle checkpoint regulator pChk2, were evaluated at 1 h by western blotting. Cellcycle distribution was measured by flow cytometry, the treated cells were sorted into G0/G1-G2/M with MoFLo and expression of DNA repair and senescence related genes was quantified by qPCR at 24 h and 5 days. In vivo, cell cycle activation, DNA damage and senescence were assesed in CEnCs using whole mount corneas (+/-UVA) of wildtype (WT) and Atm-null mice.
Results: Acute treatment with UVA+4-OHE2 resulted in (i) an early and increased activation of pATM (3fold), γH2AX (2-fold), and pChk2 (2.5-fold), and (ii) greater cell-cycle arrest in G2/M phase (1.5-fold), in NQO1-/- compared to NQO1+/+ cells. Loss of NQO1, seen in FECD, also led to higher upregulation of DNA repair genes, LIG3 (2.5-fold), NEIL2 (5-fold), TOP3A (20-fold), and XPC (5.5-fold) in G2/M phase indicating that cell-cycle arrest and activation of DNA repair is more pronounced in FECD. Addition of ATMi suppressed G2/M arrest and DNA repair upregulation, demonstrating that early ATM activation is critical for initiation of DDR. Likewise, UVA induced cell-cycle reentry, γH2AX foci, and senescence-associated heterochromatin, were reduced in Atm-null mice. Chronic treatment caused ATM-mediated arrest in G0/G1 phase of cell cycle in both NQO1+/+ and NQO1-/- cells. However, a markedly reduced expression of DNA-repair genes, LIG3 (2fold), NEIL2 (5-fold), TOP3A (4-fold), and XPC (3-fold) was noted in G0/G1 phase of NQO1-/-, compared to NQO1+/+ cells, signifying that DNA repair is severely diminished in the absence of NQO1 chronically. Interestingly, use of ATMi enhanced DNA repair in G2/M phase and averted senescence in chronic cellular model of FECD lacking NQO1.
Conclusions: We demonstrate that under acute conditions, increased activation of ATM is indeed beneficial for cells, leading to G2/M cell-cycle arrest, increased DNA repair and protective senescence. However, chronic stress leads to greater DNA damage, G0/G1 arrest of cell-cycle with significantly decreased DNA repair, cytotoxic senescence and an onset of FECD. We suggest that ATM-driven modulation of cell cycle and DNA repair can potentially provide a novel therapeutic strategy against FECD.
Candidate: Shreya Bhatt
Poster #: 4
Investigating Visual Photosensitivity and Dry Eye Symptoms in Individuals With Traumatic Brain Injuries
Shreya Bhatt, Mariela C. Aguilar, Heather A. Durkee, Alex Gonzalez, David Valdes Arias, Shivam P. Patel, Cornelis Rowaan, Gemayaret Alvarez, Barry E. Hurwitz, Byron L. Lam, Elizabeth R. Felix, Jean-Marie A. Parel, Anat Galor
Purpose: Individuals can experience a traumatic brain injury (TBI) from a wide variety of causes including falls and motor vehicle collisions that can result in an array of consequences ranging from minor concussions to profound disability. A prevalent symptom associated with TBI is photophobia, which can vary in intensity. This study aimed to quantify the severity of dry eye symptoms and visual photosensitivity sequelae in individuals who have suffered TBI by employing validated questionnaires and evaluating visual sensitivity to light.
Methods: Forty-six participants with TBI (average age 42.0±15.0 years) and forty-six healthy participants (average age 32.5±13.4 years) attended two study visits (V1 and V2) spaced at least one month apart. At both visits, the participants completed the following questionnaires to evaluate their symptoms: the Ocular Surface Disease Index (OSDI, range: 0-100), the 5 Item Dry Eye Questionnaire (DEQ-5, range: 0-22), the Neuropathic Pain Symptom Inventory modified for the Eye (NPSI-Eye, range: 0-100), and the Visual Light Sensitivity Questionnaire-8 (VLSQ-8, range: 8-40). The participants also underwent evaluation with the Ocular Photosensitivity Analyzer (OPA) to determine their Visual Photosensitivity Threshold (VPT, range: 04.5 log lux). Intraclass correlation coefficients (ICCs) were used to assess the consistency of measures between the two visits, while Pearson correlations were computed to examine the relationship between VPT and questionnaire scores.
Results: TBI participants when compared to healthy participants reported significantly higher mean scores on the OSDI (10.2±10.5 vs. 2.2±3.3 in V1, 12.3±10.3 vs. 2.4±3.5 in V2; p<0.001), DEQ -5 (7.8±5.4 vs. 3.5±3.5 in V1, 7.7±5.1 vs. 3.8±3.3 in V2; p<0.001), NPSI -Eye (8.1±14.4 vs. 1.0±3.3 in V1, 12.2±16.6 vs. 1.3±2.8 in V2; p<0.001), and VLSQ-8 (21.1±8.3 vs. 11.5±3.4 in V1, 21.8±8.0 vs. 11.3±3.7 in V2; p<0.001) indicating more severe dry eye symptoms. The average VPT of TBI participants was significantly lower than healthy participants (1.8±0.9 vs. 2.6±0.8 log lux in V1, 1.4±0.8 vs. 2.3±0.8 log lux in V2; p<0.001), indicating greater visual photosensitivity in this group.
Conclusions: This study highlighted the substantial impact of TBI on dry eye symptoms and visual photosensitivity. Based on the ocular symptomatology questionnaires and OPA VPT measurements, participants with TBI displayed significantly more severe dry eye symptoms and visual photosensitivity than healthy participants. These findings suggest that the questionnaires and OPA VPT could be effective tools for assessing symptom severity and evaluating intervention outcomes in this population. Additional research is required to elucidate the mechanisms driving photophobia in TBI patients and to investigate targeted treatments for its debilitating sequelae.
Candidate: Raluca Bievel-Radulescu
Poster #: 5
A New Resource for Eye Banks: Post- SMILE Stromal Corneal Lenticules
Raluca Bievel- Radulescu, Elena Paveggio, Stefano Ferrari, Diego Ponzin
Purpose: The aim of our study is to establish a lenticule eye bank by collecting and processing stromal lenticules extracted during ReLEx SMILE refractive surgeries. These lenticules, typically discarded, will be preserved and prepared for therapeutic applications, including additive and tectonic keratoplasty, as well as scleral patches. By validating the safety and viability of the lenticules, our goal is to create a standardized, readily available resource for surgeons, promoting the widespread adoption of this innovative approach in ophthalmic treatments.
Methods: This study, approved by the Ethical Committee for Clinical Trials (CESC) of the Province of Venice and IRCCS San Camillo (262A/CESC/18.04.2023), adhered to the Declaration of Helsinki. Informed consent was obtained from 44 myopic patients (73% female, average age 33.6 years), leading to the collection of 84 stromal lenticules during SMILE surgeries. Donor selection followed criteria set by the Italian National Transplant Service, excluding those with ocular or systemic conditions. Lenticules were transported within 48 hours to the Fondazione Banca degli Occhi del Veneto in Coldix, Hyaluronic acid, Storagix, or BASE media. Thickness and diameter were measured using Optical Coherence Tomography (Casia, AS-OCT, Tomey, Japan), with the central thickness calculated by averaging three measurements within ±2 µm. Transparency was assessed using a custom setup based on a Lux meter with a pinhole technique. Histological analysis involved fixing lenticules in formaldehyde, embedding in paraffin, and staining with hematoxylin-eosin, PAS, and Masson's trichrome.
Results: 1) Thickness Measurements: Lenticule thickness increased significantly after storage in all media. Hyaluronic Acid (HA) showed the least swelling (139 µm to 180 µm, p < 0.0001), while Coldix (144 µm to 306 µm), Storagix (148 µm to 352 µm), and Base (14 µm to 345 µm) showed greater increases (p < 0.0001). Coldix caused a significantly higher increase than HA (p < 0.0001), but Storagix and Base showed no significant difference from Coldix. 2) Transparency Measurements: Transparency was slightly higher in HA-stored lenticules compared to Coldix, but the difference was not statistically significant (p=0.3770), indicating similar transparency levels between the two storage conditions. 3) Diameter Measurements: No significant difference in diameter was observed between lenticules stored in HA and Coldix (p = 0.3421), suggesting similar structural preservation in both media. 4)Histology: Histological analysis using H&E, Masson's Trichrome, and PAS staining revealed well-preserved tissue structure and morphology in lenticules stored in both HA and Coldix. The collagen network and biochemical composition remained intact, with no signs of fibrosis or abnormal polysaccharide distribution, indicating effective preservation.
Conclusions: This study successfully established a process for collecting, preserving, and analyzing stromal lenticules from SMILE surgeries. Lenticules stored in different media exhibited varying degrees of thickness changes. Transparency remained consistent across storage conditions, and histological analysis confirmed the structural and biochemical integrity of the preserved lenticules. These findings support the viability of creating a lenticule eye bank, providing a valuable resource for future therapeutic applications in ophthalmology.
Candidate: Nikolay Boychev
Poster #: 6
Sociodemographic Risks Associated With Acute Corneal Hydrops
Nikolay Boychev, Levi Kanu, Leah Margolis, Meredith Fry, Cherry Le, Veronica Ng, Jules Hutchison, Joseph Ciolino
Purpose: To identify sociodemographic risks associated with the development of acute corneal hydrops.
Methods: A retrospective case-control study of acute corneal hydrops patients at Mass Eye and Ear was conducted. Potential cases were identified by ICD-10 code using the Research Patient Data Registry and reviewed for inclusion. Sociodemographic and biometric data spanning 2016-2022 was extracted. Data was analyzed by t-test and chi-squared test.
Results: Among 758 patients with unstable keratoconus, 113 (14.9%) developed acute corneal hydrops. Compared to those without hydrops, the hydrops group had a higher percentage of Black patients (30.1% vs 13.8%, P<0.0001), a higher proportion of non-English speakers (9.0% vs 6.0%, P=0.04), a higher unemployment rate (22.4% vs 12.5%, P<0.0001), a lower rate of private health insurance (64.9% vs 82.8%, P<0.0001), and showed a trend towards a worse area deprivation index (36.3±32.9 vs 30.5±30.1, P=0.06). Developmental delay (17.7% vs 3.2%, P<0.0001) and atopy (48.2% vs 30.4%, P=0.0002) were more prevalent in the hydrops group, and these patients had a higher average BMI (34.1±10.0 vs 29.2±8.1, P<0.0001).
Conclusions: Our findings indicate significant associations between sociodemographic risks and the incidence of acute corneal hydrops. A large multi-site study to determine the clinical implications of these results is underway.
Candidate: Enchi Chang
Poster #: 7
Outcomes of Using the Biovance® 3L Ocular Human Amniotic Membrane Allograft for Corneal Epithelial Defects
Enchi Chang, Nandini Venkateswaran
Purpose: A novel three-layer acellular amniotic membrane, the Biovance® 3L Ocular Human Amniotic Membrane Allograft by Verséa Therapeutics, has become recently available and has not been widely studied in clinical practice. As such, we aim to evaluate the use of this new amniotic membrane allograft in patients with various corneal pathologies or undergoing corneal procedures.
Methods: This was a retrospective chart review of 7 eyes from 6 patients who underwent amniotic membrane transplantation (AMT) with the new Biovance® 3L Ocular Human Amniotic Membrane Allograft between January and October 2023. Outcome measures included best-corrected visual acuity, resolution of the epithelial defect, and any complications from the amniotic membrane transplantation.
Results: This study included 7 eyes from 6 patients, ages 31 – 80, with follow-up ranging from 5-41 weeks. Corneal diagnoses treated were recurrent corneal erosions, Salzmann’s nodular degeneration and persistent epithelial defects in prior corneal grafts. The visual acuities for 6 eyes at their last visits were improved or stable compared to their pre-AMT placement visit and ranged from 20/25 to hand motion. The AMT dissolved within 1 week with resolution of the epithelial defect for most eyes. Complications included AMT incorporating into the epithelium, a late recurrent epithelial defect with elevated intraocular pressure, and progressive corneal graft thinning.
Conclusions: The Biovance® 3L amniotic membrane is a safe, well-tolerated and effective for the treatment of corneal epithelial defects due to various corneal pathologies or corneal procedures. Complications were related to the graft incorporating into the epithelium, recurrent epithelial defect, and corneal graft thinning.
Candidate: Se Hyun Choi
Poster #: 8
Development of a Comprehensive Dry Eye Management App: Key Insights From Patient and Ophthalmologist Surveys in South Korea
Se Hyun Choi, Daejoon Alex Hwang
Purpose: Dry eye syndrome is a multifaceted condition characterized by tear film instability, hyperosmolarity, inflammation, and damage to the ocular surface. Although various diagnostic tools have been developed to measure these factors, there is often insufficient time to perform comprehensive testing or to interpret the results of tests that have been conducted. Therefore, we conducted a survey to identify the elements that doctors and patients consider necessary for dry eye management and aim to develop an application that allows users to input and interpret comprehensive dry eye results.
Methods: A comprehensive survey was conducted with 55 dry eye patients and 44 ophthalmologists in South Korea to assess the need for a dry eye management application. Based on the findings, an initial version of the application was developed for the Android system, incorporating features for inputting OSDI, Schirmer test, and BUT results.
Results: Patients' ages ranged from under 20 to over 70, with the majority in their 50s (27.3%) and predominantly women (76.5%). Most patients (74.5%) and ophthalmologists (54.5%) preferred Android OS for their phones. There was a high demand for the application, with 98.2% of patients and 70.5% of ophthalmologists expressing interest. Key desired features included MMP9 (50.9%) and the Schirmer test (41.8%) among patients, and OSDI (90.6%) and BUT (87.5%) among ophthalmologists. Time constraints in clinics led to the underutilization of these diagnostics: 50% of ophthalmologists used OSDI in less than 10% of new cases, and 31.8% reported being unable to conduct adequate tests for more than half of their patients. More than 80% of ophthalmologists were willing to use an app that includes OSDI input. Based on these results, we developed an initial application for Android OS that includes input for OSDI, Schirmer test, and BUT.
Conclusions: In conclusion, our survey reveals a significant demand for a comprehensive dry eye management tool among both patients and ophthalmologists. The developed Android prototype application, which integrates OSDI, Schirmer test, and BUT results, is poised to meet this need by facilitating more efficient and effective management of dry eye disease.
Candidate: In Young Chung
Poster #: 9
Structural and Functional Characteristics of Glaucoma in Patients With Boston Keratoprosthesis Type 1
In Young Chung, Song Luo, Mengyu Wang, Chhavi Saini, Thomas H. Dohlman, Eleftherios I. Paschalis, Lucy Q. Shen
Purpose: To assess the structural and functional characteristics of glaucoma in patients with Boston keratoprosthesis type 1 (KPro) and determine if these features align more closely with primary open-angle glaucoma (POAG) or primary angle-closure glaucoma (PACG).
Methods: This study included 65 adult KPro patients from Massachusetts Eye and Ear who underwent spectral-domain optical coherence tomography (SD-OCT) retinal nerve fiber layer (RNFL) imaging. Due to incomplete data, 48 of these patients were included in Humphrey visual field (HVF) testing analysis. RNFL thickness (RNFLT) in four quadrants and HVF total deviation (TD) values at 52 test locations were compared between KPro patients, patients with POAG (n=4110) and patients with PACG (n=283). Statistical comparisons were made using Student’s t-test and Χ² test, with linear regression applied to adjust for average RNFLT for OCT measurements and to adjust for mean deviation (MD) for visual field (VF) data.
Results: Of the 65 KPro patients, 40% were female, and 75.4% identified as White, with a mean age±SD of 66.4±13.2 years. KPro patients had a thinner average RNFLT (70.35±21.76 µm) compared to PACG (77.09±20.16 µm; P=0.025) and a similar average RNFLT compared to POAG (70.65±13.91 µm; P=0.911). KPro patients had thinner adjusted RNFL in the superior and inferior quadrants and less thinning in the temporal quadrant compared to PACG. They also had thinner superior RNFL and less temporal thinning than POAG. KPro patients showed worse diffuse VF function (HVF MD -15.4±8.9 dB) than POAG (-7.5±6.9 dB; P<0.001) or PACG (-7.7±7.9 dB; P<0.001). After adjusting for MD, they had slightly lower TD values in superior and inferior paracentral locations than PACG, and lower inferior paracentral and higher superior arcuate TD values than POAG.
Conclusions: In this study involving a relatively large number of KPro patients, we showed diffuse RNFL thinning in KPro eyes worse than PACG, while the pattern of structural RNFL thinning in quadrants differed from both POAG and PACG. In visual field assessment, KPro eyes showed worse overall functional loss than POAG and PACG. However, the pattern of VF loss in KPro eyes was similar to PACG. These findings suggest that KPro patients may exhibit distinct patterns of optic nerve damage from glaucoma, highlighting the need to obtain and monitor both structural and functional changes in suitable patients. Further investigation into the mechanisms and patterns of glaucomatous optic nerve damage in eyes with keratoprosthesis is needed.
Candidate: Neha Deshpande
Poster #: 10
Transcriptome Analyses of Human Corneal Endothelial Cell Lines Derived From Patients With Fuchs Endothelial Corneal Dystrophy
Neha Deshpande, Shazia Ashraf, Shan Zhu, Stephan Ong Tone, Ula V. Jurkunas
Purpose: Fuchs Endothelial Corneal Dystrophy (FECD) is an age-related disorder that affects about 4% of the population over the age of 40 years and is genetically associated with CTG repeat expansion in Transcription factor-4 (TCF4) gene. Although both genetic variants as well as environmental factors like ultraviolent-A light (UVA) have been reported to cause FECD, there are no pharmacological treatments due to the lack of understanding of disease pathogenesis. The purpose of this study is to evaluate the gene expression changes in the corneal endothelial (CE) cells from FECD tissues with or without CTG repeat expansions in TCF4 and thereby understand the disease-causing molecular mechanisms of FECD.
Methods: We performed RNA-sequencing (RNAseq) on Illumina HiSeq 2500 instrument (Illumina) using three normal CE cell lines and seven FECD cell lines, including 3 generated from patient tissues with TCF4 repeat expansions (FECD-R) and 4 from non-expanded patient tissues (FECD-NR). Differential expression analysis was performed using the EdgeR method and genes were classified as differentially expressed based on the cutoffs of 2-fold change in expression value and false discovery rates (FDR) below 0.05. The RNA seq datasets were subjected to Ingenuity Pathway Analysis (IPA) (Qiagen Inc.) and the top canonical pathways and upstream regulators were reported. mRNA expression analysis and western blotting were used to validate genes of interest from the datasets.
Results: Transcriptomic profiles of all 7 FECD cell lines compared to normal, revealed 214 differentially expressed genes (DEGs) with 193 down- and 21 up-regulated genes. IPA detected hepatic fibrosis and endothelial-mesenchymal transition pathways as top canonical pathways. We identified transcriptional regulator genes, MAFB, TFAP2B, and POU6F2 to be differentially downregulated in FECD. 48 common DEGs including β-estradiol, TGF-β1, AHR, and transcription regulators like CEBPA and SMARCA4, were detected in both FECD-R and FECD-NR. 29 DEGs were identified only in FECD-R, compared to normal cells. Canonical pathways like tryptophan and melatonin degradation, Wnt signaling, Aryl hydrocarbon receptor signaling, mitochondrial dysfunction, were also highly enriched in FECD.
Conclusions: The enrichment of hepatic fibrosis and endothelial-mesenchymal transition, both known to contribute to guttae formation, amongst the top canonical pathways in FECD cell lines suggests that the classic pathways defining FECD phenotype are still preserved in the immortalized cell lines obtained from patient tissues. The involvement of β-estradiol and TGF-β1, previously implicated in FECD, as upstream regulators in both FECD-R and FECD-NR groups, suggests their possible role in the unifying mechanism of FECD pathogenesis. Overall, our data identify genes and potential pathways that are altered during disease progression and therefore represent therapeutic targets for FECD. Further investigation of the DEGs in animal models is warranted to validate these data.
Candidate: Hongyu Duan
Poster #: 11
Novel Cytokine CSBF: An Endogenous Regulator of Inflammation in Dry Eye Disease and its Therapeutic Potential
Hongyu Duan, Baikai Ma, Wenling Han, Hong Qi
Purpose: Dry Eye Disease (DED) is a chronic inflammatory condition triggered by multiple factors. The corneal epithelium, being in direct contact with environmental stressors, serves as the starting point for the vicious cycle of inflammation in DED. Current anti-inflammatory treatments for DED largely consist of immunosuppressants that act in the later stages of the inflammatory response by inhibiting T-cell activation. However, these treatments often come with significant side effects and a slow onset of action. Therefore, identifying endogenous anti-inflammatory molecules and upstream therapeutic targets in the inflammatory response is crucial for advancing DED treatment.
Methods: This study investigated the expression of a novel cytokine, Colon-derived SUSD2 binding factor (CSBF), in DED using clinical cross-sectional studies, animal models, and cell models. To elucidate the role of CSBF in DED, wild-type (WT) and Csbf -/- (knockout, KO) mice were exposed to desiccating stress combined with subcutaneous scopolamine injection to induce a mixed model of DED. The DED phenotype was evaluated using the phenol red thread test to measure tear secretion, corneal fluorescein staining to assess corneal damage, and flow cytometry to analyze CD4+ T cell subset infiltration in draining lymph nodes and ocular surface tissues. Bone marrow adoptive transfer experiments were conducted to determine the cellular source of CSBF's function in DED. To explore the therapeutic potential of recombinant CSBF protein in DED, either PBS or recombinant CSBF protein was administered as eye drops to dry eye mice, followed by assessment of the DED phenotype. Additionally, an immortalized human corneal epithelial cell line (HCEC) was pretreated with PBS or human recombinant CSBF protein and cultured under hyperosmolar conditions (500 mOsM) to measure inflammatory cytokine levels.
Results: CSBF levels were found to be elevated in the tears of DED patients and were negatively correlated with inflammatory cytokine levels. CSBF expression was also upregulated in the corneal tissues of DED mice and in hyperosmolar-stimulated HCE-T cells. KO mice showed increased corneal damage and a higher proportion of T helper 17 (Th17) cells in the draining lymph nodes, conjunctiva, and lacrimal glands after DED induction. KO recipient mice receiving bone marrow cells from WT donors exhibited more sev ere corneal epithelial damage and a higher proportion of conjunctival Th17 cells compared to WT recipient mice. Therapeutically, recombinant CSBF protein eye drops significantly reduced corneal damage and ocular surface inflammation in dry eye mice.
Conclusions: CSBF, derived from corneal epithelial cells, has a protective role in DED by mitigating corneal epithelial damage and ocular surface inflammation. As an endogenous negative immune regulatory molecule, CSBF holds promising potential for clinical application in anti-inflammatory therapy for DED.
Candidate: Eileen (Yilin) Feng
Poster #: 12
Minimizing Eye Drop Burden After Cataract Surgery in Patients With Retinitis Pigmentosa
Yilin (Eileen) Feng, Sila Bal, Jovany J. Franco, Roberto Pineda
Purpose: To describe the outcomes and complications of dropless cataract surgery (DCS) in patients with retinitis pigmentosa (RP).
Methods: Retrospective review of patients with RP who underwent DCS performed by a single surgeon between January 2019 and January 2022 at a tertiary referral academic center. DCS was defined as intraoperative use of 0.1 mg of intracameral moxifloxacin and 0.2 mg of subconjunctival triamcinolone (40mg/ml) without post-operative supplementary steroid or antibiotic eye drops. Patients who received a topical carbonic anhydrase inhibitor following surgery were included.
Results: Twelve eyes of 10 patients with a mean age of 65.6 years and follow-up of 761 days were included. The mean baseline visual acuity was 20/184, which improved to 20/84 at final follow-up (p=0.04). There was no difference in the pre- and post-operative intraocular pressures (p=0.52). Topical dorzolamide was used in 58.3% of eyes to prevent cystoid macular edema (CME). Two eyes from one patient had chronic CME that worsened after DCS so topical prednisolone 1% and ketorolac 0.5% were added. No other eyes developed CME or required steroid or antibiotic drops. Eleven (91.7%) eyes developed posterior capsular opacification, and six eyes ultimately underwent a YAG laser capsulotomy.
Conclusions: DCS is a safe and effective alternative to traditional post-cataract surgery management to reduce drop burden in RP patients.
Candidate: Dominique Geoffrion
Poster #: 13
Inflammatory Tear Cytokine Levels in Patients With Boston Keratoprosthesis Type 1 Versus Primary Angle Closure Glaucoma
Dominique Geoffrion, Georges M. Durr, Marie-Claude Robert, Younes Agoumi, Robert K. Koenekoop, Adriana Di Polo, Mona HarissiDagher
Purpose: To characterize the difference in ocular surface inflammation between Boston keratoprosthesis (KPro) and primary angle closure glaucoma patients.
Methods: Prospective cross-sectional study of 68 eyes: 10 controls, 10 primary angle closure glaucoma without KPro (PACG), 41 KPro with glaucoma (KPro G), and 7 KPro without glaucoma (KPro NoG). A multiplex bead immunoassay measured the levels of 27 cytokines in the tear fluid of all eyes. Ancillary testing included visual acuity, intraocular pressure, anterior segment OCT and posterior segment OCT for all patients. Statistical analysis included univariable and multivariable analyses.
Results: All groups had similar age and gender distribution. Mean time from KPro surgery to tear collection was 7.9±3.5 years. Compared to PACG patients, KPro G patients had higher tear levels of IL-1RA (P <0.0001), IL-8 (P=0.002), IL-15 (P=0.003) and RANTES (P=0.001). A generalized linear model showed that KPro and angle status were significantly associated with IL-1RA (b= 7236, P<0.0001; b=-3846, P=0.005), IL- 8 (b=825.3, P=0.002; b= -550.7, P=0.03), and RANTES levels (b=12.73, P=0.0008; b=-10.76, P=0.003), respectively, after adjusting for age, gender, and glaucoma. KPro status was associated with IL-15 (b=3.344, P=0.012) after adjusting for age, gender, angle and glaucoma status.
Conclusions: Results show that KPro G eyes have a particular inflammatory profile compared to PACG. IL1RA, IL-8, IL-15, and RANTES are elevated in tear fluid of KPro G compared to PACG and may serve as biomarkers. Ocular surface inflammation in KPro eyes may be influenced by angle closure which ought to be managed earlier.
Candidate: Andrew Griswold
Poster #: 14
Spatial Regulation of the NLRP1 Inflammasome in the Cornea
Andrew R. Griswold, Antonio E. Herrera, Thomas H. Dohlman
Purpose: Inflammasomes are multiprotein complexes that detect danger signals and trigger pyroptosis, an immunostimulatory form of cell death. NLRP1 was the first characterized inflammasome. Mutations in NLRP1 cause severe autoinflammatory disease of the cornea and other barrier epithelial tissues. We have recently shown that NLRP1 is ubiquitously expressed and upon activation forms a functional inflammasome causing cell death in primary human corneal epithelial cells. Whether NLRP1 is limited to the corneal epithelium or extends into deeper corneal layers remains unknown. Here we tested whether NLRP1 can induce pyroptosis in corneal stromal fibroblasts.
Methods: The dipeptidyl peptidase 8/9 inhibitor, Val-boroPro (VbP), is a commercially available activator of the NLRP1 inflammasome. Here we treated mouse corneal fibroblasts (MK/T-1) with VbP. Pyroptotic cell death was assessed by release of lactate dehydrogenase (LDH) and interleukin-1 beta (IL-1β) into culture media at 24 hours. Publicly available single cell RNA seq data was examined to assess NLRP1 expression in the cornea.
Results: Treatment of MK/T-1 cells with VbP for 24 hours did not significantly increase release of LDH or IL1β into cell culture media as compared to DMSO-treated control cells. Single cell RNA seq data suggested NLRP1 is preferentially expressed by corneal epithelial cells.
Conclusions: Here we show that unlike corneal epithelial cells, corneal stromal fibroblasts do not undergo NLRP1 dependent pyroptosis. RNA seq data suggests that NLRP1 is likely spatially regulated to the corneal epithelium. Together this data implicates a pro-inflammatory niche for NLRP1 at the ocular surface.
Candidate: Oylum Buse Gur
Poster #: 15
Evaluation of Temperature Changes on the Ocular Surface After Intravitreal Injection Using a Thermal Camera
Purpose: This study aims to evaluate the temperature changes on the corneal surface, nasal, and temporal conjunctiva following intravitreal injection in patients with various retinal conditions, including macular degeneration, diabetic retinopathy, degenerative myopia, and retinal vein occlusion. Understanding these temperature fluctuations is crucial for assessing the ocular surface's physiological response to intravitreal injections.
Methods: A total of 15 patients diagnosed with macular degeneration, diabetic retinopathy, degenerative myopia, and retinal vein occlusion were included in this prospective study. Temperature measurements of the corneal surface, nasal, and temporal conjunctiva, along with room temperatures at the same time points, were performed using a FLIR One Edge Pro handheld thermal camera at five different time points: pre-injection, Day 1, Day 3, Day 7, and Day 10 post-injection. The distance between the thermal camera and the patient’s eye was standardized at 30 cm to ensure consistent and accurate temperature readings. The collected data were statistically analyzed to identify significant temperature changes over time using Friedman test with statistical significance set at p<0.05.
Results: There was a consistent temperature drop from pre-injection values (36.1±0.8°C) to Day 1 (35.8±0.7°C), Day 3 (35.5±1.0°C), Day 7 (35.7±0.6°C) and Day 10 (35.2±1.3°C) on the corneal surface (all p<0.05). Although similar trends were observed for nasal and temporal conjunctiva measurements, the differences were not statistically significantly different.
Conclusions: A reduction in ocular surface temperature following intravitreal injections may be associated with the anti-inflammatory effects of Anti-VEGF and intravitreal dexamethasone, with their impact increasing over time. Further studies could explore the implications of these findings on patient management in greater detail.
Candidate: Helen Gutiérrez
Poster #: 16
Refining Cell Culture of Corneal Epithelial Cells Obtained After Advanced Surface Ablation
Helen Gutiérrez, Antonio López-García, Miguel J. Maldonado, Laura García-Posadas
Purpose: In refractive surgery using the advanced surface ablation (ASA) technique, a sheet of epithelial cells from the central cornea is obtained. This study aims to maximize the potential use of these cells in in vitro models through their characterization, viability assessment, and the optimization of a cell culture protocol, with the purpose of advancing the study of ocular surface diseases.
Methods: This study was approved by the Ethics Committee of the University of Valladolid. Corneal epithelial cells were obtained from 41 patients undergoing ASA. The central cornea was exposed to 20% ethanol for 30 seconds to remove the epithelial layer. The sample was collected in a cell culture medium, and tests were performed by adding trehalose to this medium to reduce oxidative stress and increase cell viability. Initial cell viability was assessed using the LIVE/DEAD assay. Samples were embedded in OCT Compound or paraffin, sectioned, and stained to evaluate the expression of corneal epithelial (CK3, CK12), cell barrier (E-cadherin, ZO-1), and proliferative markers (Ki67) using immunofluorescence. For cell culture, the tissue was cut in half and disaggregated with trypsin/EDTA for 10 or 15 minutes. The cells were then seeded in a supplemented DMEM/F12 medium. Cell proliferation was measured with the AlamarBlue assay under several conditions: 1. Fetal bovine serum (FBS) versus human serum (HS). 2. Supplementation with 1 µM hydrocortisone. 3. Coating the culture surface with 10 mg/ml type I collagen (Col1). 4. Addition of trehalose. Cells from the disaggregated tissues were also co-cultured with corneal epithelial (IM-HCEpiC), conjunctival epithelial (IM-HConEpiC), and corneal fibroblast (P10872-IM) cell lines. Results were presented as mean ± standard deviation. A Student’s t-test was used to analyze differences.
Results: The epithelial tissue maintained high cell viability. Trehalose addition to the sample medium reduced intracellular vacuoles under hematoxylin-eosin staining. Histology showed a well-preserved structure with intraepithelial edema, corneal markers (CK3, CK12), and cell junction proteins (E-cadherin, ZO-1), with some Ki67-positive cells. Trypsinization was more efficient at 15 minutes, yielding higher cell count and viability. FBS culture increased metabolic activity 2.7-fold (p=0.001). Hydrocortisone boosted proliferation 1.9-fold, collagen coating 11-fold, and trehalose 5.3-fold (all p<0.001). Co-culture with fibroblasts and epithelial cells increased proliferation 1.5- and 2.8-fold, respectively (p<0.001).
Conclusions: The corneal epithelium removed during ASA surgery retains cell viability and the expression of key cellular markers, making it a valuable source for creating in vitro models. This study identified various factors, including the use of FBS, hydrocortisone, type I collagen, and trehalose, that can enhance corneal epithelial cell culture. These findings contribute to the development of robust in vitro models for studying ocular surface diseases.
Candidate: Ema Karakoleva
Poster #: 17
PTSD is Associated With Increased Activation of Photophobia Brain Circuits in Individuals With Chronic Ocular Pain
Ema V. Karakoleva, David Valdes, Nicholas Reyes, Chloe M. Shields, Shreya Bhatt, Sakina A. Qazi, Nicholas J. Pondelis, Elizabeth R. Felix, Anat Galor, Eric A. Moulton
Purpose: Chronic ocular pain (COP) is a prevalent condition significantly affecting quality of life. It has been linked to a higher prevalence of post-traumatic stress disorder (PTSD), a psychiatric comorbidity that may exacerbate the experience of pain. Despite this association, the underlying neurological mechanisms remain poorly understood. In this study, we aimed to explore how PTSD influences the brain’s pain processing pathways in response to light stimuli. By identifying key neurological differences between PTSD patients and controls, we sought to provide insight into the complex interplay between PTSD and COP, ultimately guiding more targeted and effective treatment strategies.
Methods: We examined the impact of post-traumatic stress disorder (PTSD) on light-induced pain processing pathways in South Florida veterans with COP (n=45, 55.6±11.6, 62.2% male, average pain level ≥1 in the past week) using functional magnetic resonance imaging (fMRI) and light-evoked pain and unpleasantness ratings (score 0-100). Subjects were grouped into two groups – PTSD patients (n=14, PTSD checklist score ≥33) and controls. Brain regions with statistically significant differences in Blood Oxygen Level Dependent (BOLD) responses to light stimuli between the two groups were identified and used for subsequent analysis. We constructed 7 masks on the standard MNI152 in FSLeyes using Regions of Interest (ROIs) extracted according to the cortical Harvard –Oxford probabilistic atlas. Masks were linearly aligned to the MNI-152 space using FSL’s Linear Image Registration Tool (FSL-flirt), and a linear registration approach was used to preserve native geometry. fMRI activation maps, reflecting the statistical differences between low and high PTSD groups, were voxelwise thresholded at Z > 2.3 and then masked for the ROIs to identify significant activations within the predefined brain regions.
Results: Compared to controls, individuals with PTSD exhibited increased BOLD responses to light stimuli in several brain regions, including the left amygdala (37.1% activated voxels), left primary somatosensory cortex (13.8% activated voxels), bilateral central opercular cortex (17.5% activated voxels), left hippocampus (6.9% activated voxels), bilateral lateral occipital cortex superior (9.0% activated voxels) and inferior (31.2% activated voxels) divisions, and right midcingulate cortex (9.9% activated voxels). Additionally, PTSD subjects reported generally higher, though statistically non-significant, levels of eye pain and unpleasantness.
Conclusions: Our study reveals that PTSD affects the brain's response to light-induced pain in individuals with chronic ocular pain (COP). By showing increased neural activity in specific brain regions, our findings enhance understanding of the interplay between PTSD and COP. These insights are crucial for developing targeted treatments that address both PTSD and chronic ocular pain, potentially improving outcomes for affected individuals. Future research should build on these results to further elucidate the contributing neural mechanisms and refine therapeutic treatment approaches.
Candidate: Agnieszka Kuligowska
Poster #: 18
Modern Diagnostic and Treatment Strategies for Avellino Dystrophy –A Case Study
Agnieszka Kuligowska, Oskar Lorenc, Anna Machalińska
Purpose: Granular corneal dystrophy type 2 (GCD2/Avellino) is an epithelial/stromal TGFBI dystrophy causing increased irregularity of the corneal surface, progressive deterioration of visual acuity and mild erosions. The diagnosis of GCD2 is based on a clinical examination supported by confocal microscopy (IVCM) and anterior segment OCT (AS-OCT). The treatment includes surgical interventions, i.e.: deep anterior layered keratoplasty (DALK) and laser - therapeutic photokeratectomy (PTK) – importantly both of them saving the patient's own endothelium. The aim of this study was to analyze the final effects of DALK and PTK and to define the dynamic of clinical improvement in both methods in GCD2.
Methods: 30-year-old female patient with progressive deterioration of visual acuity, strong photophobia and chronic pain caused by recurrent erosions was diagnosed with GCD2 of different degrees of advancement in the right (RE) and the left eye (LE). Visual acuity in the LE was 0.2 and in RE was 0.4 Snellen. Central corneal sensitivity (CS) was noted in both eyes at 4 mm of nylon thread length (NTL)using Cohet-Bonnett aesthesiometer, central corneal thickness (CCT) was 680 µm and 555 µm, and endothelial cell count (ECC)was 3478 cc/mm2 and 3169 cc/mm2, respectively. Due to the penetration of the amyloid and hyaline deposits below 260 µm into the corneal stroma DALK procedure in the LE was performed. DALK corneal graft diameter was 8.25 mm and the cutting depth in the recipient bed was 450 µm. Suture removal took place 12 months after surgery. The depth of the deposits in the RE was 125 µm what resulted in the decision to conduct the transPTK, which was performed using Schwind AMARIS 1050S excimer laser with th e following laser settings: depth of ablation: 90 µm, diameter: 8,5 mm, time: 40 seconds and was followed by 40 seconds mitomycin (MMC) exposition for haze prophylaxis. During regular follow-up visits after 1,3 and 6 months after post-DALK suture removal in LE and transPTK in RE best corrected visual acuity (BCVA), CS, mean astigmatism (MA), higher order aberrations (HOA) and CCT in AS-OCT were evaluated. Corneal reepithelialization was evaluated weekly until full using IVCM.
Results: Complete re-epithelialization in the RE occurred after 4 weeks. BCVA improved gradually (0.4 after 1, 0.6 after 3 and 0.9 after 6 months), MA increased in the 1st month (0.67D) and returned to the pre-op (0.27D) values. HOA decreased and then remained stable (0.22D pre-op, 0.15-0.17D post-op). In the LE, BCVA improved instantly (0.6 after 1 and 3, 0.7 after 6 months). MA increased in the 1st month (1.28D) and returned to the pre-op (0.87D) values. HOA finally decreased slightly (0.46 pre-op, 0.45 after 1, 0.51 after 3 and 0.39D after 6 months). Both in the RE and LE there were temporary CS disturbances during follow -up visits and then CS improved finally to 5 in the RE and 4.5 NTL in the LE.
Conclusions: PTK is a safe alternative to DALK in eyes with low-grade GCD2 and it should be considered every time before deciding on surgical treatment. Nevertheless, prolonged epithelial healing after PTK in GCD2 shouldn’t be overlooked. The role of early laser intervention is important, as it might significantly postpone the need for surgical procedure and allow to maintain functional VA. In patients with a high stage of GCD2 and the presence of the opacities in the deep stromal layers, DALK remains the method of choice. It should be also emphasized that saving the patient's own endothelium in both methods significantly reduces the risk of complications such as graft rejection or corneal decompensation.
Candidate: Hayoung Lee
Poster #: 19
Therapeutic Effects of Decellularized Extracellular Matrix-Based Adhesive Restorative Material on the Corneal Regeneration in a Model of Corneal Alkali Burn
Hayoung Lee, Changmin Kim, Eun-Ah Ye, Yeji Yoon, Minah Jeon, Ji Yoon Park, Ryunhee Lee, Younhee Chae, Ju Young Park, Jinah Jang, Hun Lee
Purpose: We aimed to develop an alkali corneal burn model and investigate the therapeutic effects and potential applications of gelatinized cornea-derived decellularized ECM (GelCODE) for treating alkali corneal burns.
Methods: We generated a rat model of alkali corneal burn by applying 0.5N NaOH to the ocular surface for 30 seconds. Afterward, we applied porcine cornea-derived GelCODE to the damaged cornea and initiated a crosslinking reaction using 450-500 nm blue light for 1 minute. Ocular observations were conducted for up to 4 weeks post-treatment to assess changes in corneal erosion and abrasion, neovascularization, corneal opacity, and corneal thickness. After sacrifice, the eyes were enucleated for tissue analysis and fixed in formalin, and immunohistochemistry (IHC) was performed on the tissue prepared on slides. Additionally, we used an open field test to evaluate visual impairment-related mobility in the rat model of alkali corneal burns.
Results: In the GelCODE-treated group, the mean score of corneal opacity and scarring decreased from 3.5(SD=0.4) to 1.7(SD=1.7) compared to the untreated group. Histological analysis revealed positive effects of GelCODE on stromal fibrosis and tight junction integrity. Although the alkali burn increased IL-1β expression, GelCODE suppressed the expression of IL-1β. The open field test showed an average mobility improvement of 543 cm (SD = 190) to 903 cm (SD = 184) in the treated group, suggesting a relative recovery of visual impairment. Overall, GelCODE promoted wound repair by reducing inflammation, aiding matrix regeneration, and preserving corneal transparency.
Conclusions: The ECM-based tissue recovery adhesive derived from the porcine cornea played a crucial role in stimulating corneal regeneration in alkali corneal burns by reducing corneal scarring, preserving the epithelial and stromal layer structures, and improving corneal transparency.
Candidate: Jie Liu
Poster #: 20
Minimally Invasive Keratoprosthesis (mi-KPro) for Vision Restoration After Severe Chemical Injury
Jie Liu, Jyoti Sharma, Thomas H. Dohlman, Chengxin Zhou, Peter York, Fengyang Lei, Robert Woods, Claes Dohlman, James Chodosh, Roberto Pineda, Eleftherios I. Paschalis
Purpose: Approximately 1.5-2 million patients globally become corneal blind every year, of which a significant proportion is not amenable to standard corneal transplantation. To this end, artificial corneas have become the mainstay of treatment of severe corneal blindness. More than 20,000 eyes have been treated with the most successful FDA approved artificial corneas, the Boston Keratoprosthesis (B-KPro) and the Lucia. However, complications, such as, ocular hypertension, glaucoma, endophthalmitis and retroprosthetic membrane (RPM) formation often compromise long-term outcomes and cause terminal blindness. To overcome these limitations, we developed a minimally invasive KPro (mi-KPro) device, to minimize the aforementioned complications while being amenable for patients with severe ocular pathologies.
Methods: Corneal alkali and acid injury models were employed in rabbits, using 2N NaOH (n=12) or 2N HCl (n=12), respectively. One month after injury, animals underwent either mi-KPro surgery (n=12) or penetrating keratoplasty (PKP) (n=12). Animals were followed with anterior and posterior eye optical coherent tomography (OCT), photography, and intraocular pressure (IOP) with cannulation at baseline and monthly for 12 months. At 12 months, rabbits were euthanized and both the eyes and optic nerves were enucleated for histological analyses.
Results: Eye implanted with the mi-KPro had an excellent anatomic retention for 12 months and minimal complications as compared to standard keratoplasty that exhibited graft rejection within 3 months. None of the mi-KPro implanted rabbits developed ocular hypertension, while retinal thickness and optic nerve cup to disc ratio remained unchanged, as compared to baseline OCT measurements. In contrast, PKP control animals exhibited significant retinal thinning (n=6, p=0.004), and showed significant loss in optic nerve axons (n=6, p=0.01), as compared to KPro implanted eyes.
Conclusions: The mi-KPro achieves excellent anatomic retention for over a year in chemically inured eye and does not lead to post-surgical IOP elevation, glaucoma, PRM, or infection. This translates to preservation of the retina and optic nerve at 1 year after injury suggesting superiority in the treatment of chemically injured eyes, as compared to PKP or historical data from rabbit B-KPro surgeries. The pre-clinical safety and efficacy profile of the mi-KPro is exception and supportive of further evaluation in patients.
Mert Mestanoglu, Antonia Howaldt, Mario Matthaei, Felix Bock, Björn Bachmann, Claus Cursiefen
Purpose: Central geographic subendothelial collagen deposits in the form of a fibrillar layer (FL) are present in about 80% of advanced Fuchs endothelial corneal dystrophy (FECD) eyes. In a previous study with a smaller cohort, we have shown that FL positive FECD eyes have increased central corneal thickness compared to FL negative eyes. However, the clinical significance of these Descemet membrane changes is so far unknown. This study aimed to investigate if the presence and features of FL correlate with t he tomographic features of subclinical corneal edema in FECD.
Methods: FECD eyes scheduled for DMEK or triple DMEK surgery and with high quality preoperative Scheimpflug imaging were included in this retrospective monocenter study. Corneal densitometry, pachymetry and posterior elevation maps were exported. FL status was determined through corneal densitometry maps. FL area and caliper diameters and the three tomographic features of corneal edema (loss of parallel isopachs in the pachymetry map, displacement of the thinnest point of cornea, focal area of posterior surface depression) were evaluated and correlated.
Results: A total of 306 patients could be included. 247 eyes (80.7%) were FL positive, and 59 eyes (19.3%) were FL negative. In 219 FL positive eyes (88.6 %) 2 or 3 of the 3 tomographic features were present, whereas in only 7 (11.9%) of the FL negative 2 or 3 of the tomographic features was present. Compared to FL-negative eyes, FL-positive eyes showed higher positive proportions of all three criteria of (subclinical) corneal edema as well as higher overall scores. Correlation analysis showed weak correlation of displacement of thinnest point and FL horizontal caliper diameter (r=0.133, p=0.037) and FL maximum caliper diameter (r=0.130, p=0.041), respectively.
Conclusions: FL-positive eyes demonstrate higher scores of tomographic features of (subclinical) corneal edema. The FL identified by Scheimpflug backscatter imaging may therefore represent a morphologic marker of more advanced FECD status. Further studies are needed to evaluate the diagnostic and prognostic value of FL in FECD.
Candidate: In Hee Moon
Poster #: 22
Analysis of Tear Proteome and Clinical Correlations in Patients With Dry Eye Disease
In Hee Moon, Chae-Eun Moon, Kyung Yul Seo, Yong Woo Ji
Purpose: This study aims to evaluate the clinical characteristics and proteomic profiles of patients with dry eye disease (DED). By understanding the correlation between clinical parameters and tear protein expression, the study seeks to uncover insights into the pathophysiology of DED and guide more effective, individualized therapeutic approaches.
Methods: Seventeen patients diagnosed with DED were enrolled at Severance hospital, Yonsei University College of Medicine. Clinical evaluations included tear breakup time (TBUT), tear meniscus height (TMH), corneal staining score (CSS), and conjunctival redness using the Efron grading scale. LipiView® was used to measure lipid layer thickness (LLT), while meibomian gland dysfunction (MGD) was assessed through meibomian gland expression (MGE) and meibum quality (MQ). Individual tear samples were collected and analyzed using proteomic methods, including principal component analysis (PCA) and gene ontology (GO) analysis to identify significant protein changes and their correlation with clinical parameters. Statistical analyses such as Pearson correlation, Mann-Whitney U test, and Chi-square test were performed using SPSS version 23.0 and Python. Proteomic data were obtained using Nano RSLC Ultimate 3000 and QExactive Orbitrap HF-X, followed by data-dependent acquisition (DDA) and label-free quantification (LFQ).
Results: The study included 17 patients (mean age 35.29 ± 11.40 years, 82.4% female). Key clinical parameters observed were TBUT (3.62 ± 1.65 seconds), TMH (0.20 ± 0.17 mm), and CSS (0.47 ± 0.60). Conjunctival redness was graded as 1.37 ± 0.59 for the bulbar conjunctiva and 1.58 ± 0.54 for the palpebral conjunctiva. LLT measured 63.06 ± 24.07 nm. MGE and MQ were recorded as 0.35 ± 0.59 and 1.27 ± 0.62, respectively. Individual proteomic analysis identified 863 proteins after filtering, with significant correlations found between specific proteins and clinical parameters. Notably, proteins associated with immune response-activating cell surface receptor signaling pathways showed significant differences.
Conclusions: This study demonstrates the utility of combining clinical and proteomic data to enhance the understanding of DED. Proteomic approach in DED patients showed significant correlations between tear proteins and clinical severity, supporting the potential of tear proteome analysis in understanding DED's underlying mechanisms and guiding personalized treatment. Further research is needed to validate these findings and explore their therapeutic implications.
Candidate: Guillaume Mullie
Poster #: 23
Comparison of Outcomes Between the Ahmed Glaucoma Valve and the Baerveldt Glaucoma Implant in Eyes With Boston Keratoprosthesis
Guillaume Mullie, Dominique Geoffrion, Joseph R. Hakim, Younes Agoumi, Mona Harissi-Dagher
Purpose: To compare two frequently used aqueous shunts for the treatment of glaucoma in eyes with Boston keratoprosthesis type 1 (KPro).
Methods: Retrospective comparative study of 37 eyes (36 patients). 32 eyes received the Ahmed FP7 valve (AGV) and 5 eyes received the Baerveldt 101- 350 implant (BGI) at the same time or after KPro. Primary outcome was shunt failure (intraocular pressure [IOP] outside 6-21 mmHg or reduced <20% from baseline for 2 visits, severe vision loss or de novo glaucoma surgery). Secondary outcomes were IOP, topical medication use, and postoperative complications.
Results: At 5 years, the cumulative probability of failure was 55% for AGV and 80% for BGI (P=0.204). The most common cause of failure was the need for additional glaucoma surgery (48%). Mean IOP decreased in AGV eyes by 27% (22 to 16 mmHg) at 5 years, and in BGI eyes, by 21% (19 to 15 mmHg) (P=0.607).
Medications per eye increased by 2% at 5 years in AGV, while they decreased by 20% in BGI (P=0.281). The major complication for both groups was high IOP (22%).
Conclusions: Both shunts were effective at reducing the IOP in KPro. The BGI had a higher failure rate and lower IOP on fewer glaucoma medications compared to the AGV.
Candidate: Mustafa Kemal Özaslan
Poster #: 24
The Influence of Different Eye-Rubbing Techniques on Corneal and Anterior Segment Morphology: A Comparative Analysis of Knuckle, Fingertip, and Fingernail Methods
Mustafa Kemal Özaslan, Fatih Apaydin, Musacan Yalcin, Eray Atalay
Purpose: This study aims to evaluate the effects of three distinct eye-rubbing techniques knuckle, fingertip, and fingernail on corneal and anterior segment morphology in healthy volunteers, utilizing Pentacam.
Methods: Eighteen healthy volunteers participated in this study. Exclusion criteria included central corneal thickness ≤450 µm, recent contact lens use, ocular surface disease, ocular allergies, spherical equivalent ≥±3.00 D, astigmatism ≥3.50 D, corneal curvature >47 D, clinical or familial signs of keratoconus. Each eyerubbing technique was performed on separate days, at the same time, using the Oculus Pentacam device. Baseline corneal topography was recorded, which was followed by a second measurement immediately after 20 seconds of eye rubbing using the particular technique. Techniques were applied in the following sequence: knuckle (using the joint), fingertip (using the pad of the finger), and fingernail. Statistical analysis was conducted using the Wilcoxon signed-rank test, with significance set at p < 0.05.
Results: No statistically significant alterations in baseline corneal topographical parameters were observed post-rubbing across all techniques. However, a significant increase in the anterior chamber angle was noted with the knuckle technique, rising from a mean of 35.6° to 36.8° (p = 0.03). Although a minor increase in Kmax was observed following knuckle rubbing (44.1 D to 44.2 D), it did not reach statistical significance (p = 0.06).
Conclusions: This study highlights that while short-term eye rubbing, regardless of technique, does not induce significant corneal topographic changes, the knuckle technique significantly affects the anterior chamber angle. The observed increase in chamber angle may be attributed to the greater force applied during knuckle rubbing, potentially pushing the iris base posteriorly. Although the increase in Kmax w as not statistically significant, the trend suggests that repeated, forceful eye rubbing could have cumulative effects on corneal morphology over time. Future studies should further explore the long-term implications of habitual eye rubbing on corneal integrity.
Candidate: Calin Pater
Poster #: 25
A Double-Masked, Randomized, Placebo-Controlled, Parallel-Group, 12-Week, Phase 2 Study to Investigate the Safety and Efficacy of Ripasudil (K-321) Eye Drops After Descemetorhexis in Patients With Fuchs Endothelial Corneal Dystrophy
Kathryn A. Colby, Friedrich E. Kruse, Gregory Moloney, José Luis Güell, Jesper Østergaard Hjortdal, Daniel Francis P. Larkin, Sophie X. Deng, Sadeer B. Hannush, Ula V. Jurkunas, Tsutomu Inatomi, Noriko Koizumi, Shona Pendse, Kazuhito Suehira, Hideki Sugan
Purpose: Fuchs endothelial corneal dystrophy (FECD) has in the past been considered a disease underpinned by weak and deficient endothelial cells (ECs) leading to corneal oedema, corneal opacity and severe loss of visual acuity. In previous decades, transplantation was reserved for these patients, but with the development of Descemet membrane endothelial keratoplasty (DMEK), operations have been taking place much earlier in the course of disease, and this is continuing with Descemet's Stripping Only (DSO). There is a need for medication that can speed healing after DSO. Kowa is pursuing development of ripasudil for the indication of treatment after DSO in patients with FECD as an alternative to corneal transplantation.
Methods: We conducted a Phase 2, multi-center, double-masked, randomized, parallel-group, placebocontrolled, 2-period study with 65 patients to investigate the efficacy and safety of ripasudil (0.4% QID and 0.4% BID) in patients with FECD after DSO.
Results: The study achieved its primary endpoint by demonstrating an improvement in endothelial cell density (ECD) with ripasudil (531 cells/mm2 in the QID group (p = 0.0065), 468 cells/mm2 in the BID group (p= 0.0344) and 228 cells/mm2 in the Placebo group). In addition, there was an improved speed of corneal clearance ( 80% of patients in the QID group (p < 0.001) and 60 % in the BID group (p 0.0028) achieved complete clearance of corneal edema, as compared to 9% on placebo) and improved speed of visual recovery, after 12 weeks of treatment with ripasudil after DSO with no safety concerns. In addition, it decreases the need for medical and surgical rescue therapy.
Conclusions: DSO can be used as the initial surgical treatment in management of symptomatic endothelial disease due to FECD. The clinical value of treatment with ripasudil after DSO lies in its acceleration of recovery very soon after DSO. Phase 3 pivotal studies will establish the clinical benefit of ripasudil after DSO in earlier disease stages as an alternative to the current treatment of corneal transplantation and will include patients after both DSO with/without cataract surgery.
Candidate: Hong Qi
Poster #: 26
CMTM3 Plays a Pathogenic Role in Dry Eye Disease
Hong Qi, Yifan Zhou, Yangbo Huo, Hongyu Duan
Purpose: Dry eye disease (DED) is a chronic, non-infectious inflammatory condition affecting the ocular surface, with the highest prevalence in the world. It is characterized by ocular surface barrier damage and a persistent inflammatory response. Previous studies have indicated that the expression of CMTM3 is upregulated in corneal epithelial cells of dry eye mouse models, suggesting a potential role for CMTM3 in the pathogenesis of DED.
Methods: An experimental mouse model of DED was induced by subcutaneous injections of scopolamine hydrobromide (SCOP, 0.5 mg/0.2 mL in sterile saline) twice daily (9 AM and 5 PM) in eight-week-old female mice for 14 days. The mice were housed in a desiccator with humidity levels below 25% and exposed to continuous airflow for 24 hours. Control mice were injected with sterile saline and maintained under conditions of 50–75% relative humidity. For in vitro studies, the HCE-T cell line, verified by short tandem repeat (STR) profiling, was cultured in DMEM/F12 medium supplemented with 10 ng/mL human epidermal growth factor (hEGF), 5 μg/mL insulin, and 10% fetal bovine serum at 37 °C in a 5% CO2 atmosphere. HCE-T cells were subjected to hyperosmolar stress (500 mOsM) for varying durations. CMTM3 mRNA expression was measured at 8 hours, while protein expression was evaluated at 24 hours. The supernatant was collected for cytometric bead array (CBA) analysis.
Results: Our study demonstrated that CMTM3 expression is upregulated in both the in vivo and in vitro dry eye models at the mRNA and protein levels, as confirmed by qPCR and immunofluorescence staining. Furthermore, CMTM3 was found to exacerbate ocular surface damage in dry eye models. Knockdown or knockout of CMTM3 alleviated the phenotypes of DED in both models.
Conclusions: CMTM3 contributes to the pathogenesis of DED. Targeting CMTM3 may offer a potential therapeutic strategy for managing DED.
Candidate: Alberto Recchioni
Poster #: 27
Swept-source Optical Coherence Tomography in Ocular Surface Diseases: Repeatability and Limits of Anterior Segment Analysis
Alberto Recchioni, Abinaya Priya Venkataraman, Saaeha Rauz, Alberto Domínguez Vicent
Purpose: This study aims to assess the repeatability of anterior segment optical coherence tomography (ASOCT) across various ocular surface disorder (OSD) cohorts. It explores multiple anterior segment parameters and evaluates their accuracy within different disease groups.
Methods: A total of 239 participants across six distinct OSD groups and healthy controls underwent AS-OCT imaging using the Tomey CASIA 2 device. Anterior segment parameters including anterior chamber depth, width, angle metrics, corneal thickness, keratometry, lens vault, and others were meticulously assessed. Statistical analyses determined repeatability limits and coefficients of variation for each parameter within the different OSD cohorts.
Results: Repeatability for anterior chamber and corneal parameters remained consistent across all OSD groups, indicating minimal impact of ocular surface disease on accuracy. The coefficient of variation (CoV) for the trabecular iris-space area was about 20% for all cohorts. Ocular surface inflammation emerged as a key factor in dry eye, affecting immune-mediated and non-immune conditions alongside age-related ocular surface changes. While anterior chamber depth measurements showed variations, particularly in immune (CoV=2.5%) and non-immune (CoV=3.8%) OSD groups, parameters like anterior chamber width and angle to angle showed similar values among the cohorts. Keratometry measures remained stable despite OSD (CoV lower than 1%).
Conclusions: The Tomey CASIA 2 demonstrated reliable repeatability in measuring anterior segment parameters across diverse OSD cohorts. Despite the challenges posed by dry eye conditions, this technology shows promise in assessing OSD, suggesting that potential clinical protocols could be similar to those used for healthy controls.
Candidate: Chhavi Saini
Poster #: 28
T Cell Cytokine Profiles in Subjects With Boston Keratoprosthesis
Chhavi Saini, Kin-Sang Cho, Shuhong Jiang, In Young Chung, Maximilian Braun, Eleftherios I. Paschalis, Thomas H. Dohlman, Dong Feng Chen, Lucy Q. Shen
Purpose: We previously demonstrated that T cells are involved in the death of retinal ganglion cells and glaucomatous neurodegeneration, while tumor necrosis factor-α is elevated chronically in patients with Boston keratoprosthesis type I (KPro). Given the high incidence of glaucoma in patients with KPro, we investigated the levels of T cell-associated cytokines in the peripheral blood of patients implanted with KPro. Results were compared with controls consisting of i) healthy subjects who do not have glaucoma or KPro and ii) glaucoma patients who do not have KPro.
Methods: Healthy adult control subjects (n=34), patients with glaucoma (n=36) and patients with KPro (n=11) were prospectively enrolled. Patients with autoimmune or immunodeficiency disorders were excluded from the study. Ophthalmic and demographic data were collected for all subjects. Retinal nerve fiber layer thickness (RNFLT) was measured with optical coherence tomography. Peripheral venous blood samples were collected and used to quantify T-cell cytokines by a commercial enzyme-linked immunosorbent assay (ELISA) including cytokines such as interferon-gamma (IFN-γ), interleukin-17 (IL-17), interleukin-10 (IL-10) and transforming growth factor-β (TGF-β). Briefly, IFN-γ is a proinflammatory cytokine primarily secreted by type-1 T helper (Th1) cells to activate macrophages, control apoptosis and is associated with retinal ganglion cell death.1 IL-17 is a proinflammatory cytokine secreted by Th17 cells to induce matrix metalloproteinases (MMPs) and enable T cell infiltration into the retina. IL-10 is secreted by Th2 cells, stimulates B cell proliferation and can also be an immune suppressor. Finally, TGF-β is secreted by regulatory T cells (Treg) and suppresses autoimmunity.
Results: Controls, glaucoma and KPro subjects were similar in age, gender, and body mass index (all p>0.06). RNFLT was higher in controls (100.9±9.6µm) compared to glaucoma (75.7±12.9µm) or KPro (86.6±16.4µm, all p≤0.01) and, similar in glaucoma and KPro subjects (p=0.07). IFN-γ measurements were lower in controls (10.0±4.3pg/ml) compared to glaucoma (35.4±11.7pg/ml) and KPro (26.6±5.5pg/ml, all p≤0.01), and higher in the glaucoma vs KPro group (p=0.01). IL-17 levels were higher in glaucoma compared to controls (p<0.001). IL-10 levels were similar in all groups (p=0.75). TGF-β levels were higher in glaucoma compared to KPro (p=0.004). The ratios of Th1:Treg cytokines (IFN-γ:TGF-β) and Th17:Treg cytokines (IL17:TGF-β) were higher in glaucoma and KPro groups compared to controls (all p≤0.02).
Conclusions: We explored T cell cytokines in glaucoma patients and KPro patients. Th1 cytokine IFN-γ may be associated with glaucomatous neurodegeneration given its levels were higher in both glaucoma patients and KPro subjects, who have thinner RNFLT compared to controls. KPro patients had lower TGF-β compared to glaucoma patients, suggesting less regulatory T cell activity. Hence, it is likely that the high incidence of glaucoma in KPro patients is due to the imbalance of pro-inflammatory and anti-inflammatory T cell cytokines. Larger sample size is needed to confirm these results.
Candidate: Chloe Shields
Poster #: 29
Acute Impact of Transcutaneous Electrical Nerve Stimulation on Ocular Pain
Chloe Shields, Sakina Qazi, Ana Zaldivar, Kimberly Cabrera, Simran Mangwani Mordani, Anat Galor, Elizabeth Roy Felix
Purpose: Transcutaneous Electrical Nerve Stimulation (TENS) has been shown to be a useful adjuvant for the treatment of non-ocular chronic pain conditions. Its analgesic effect is thought to be driven by inhibition of nociceptor signaling through peripheral nerves stimulation (i.e., gate control theory). However, the impact of TENS on maladaptive nociceptive processes in individuals with neuropathic/nociplastic ocular pain (NOP) has not been examined. This study aims to evaluate the short-term analgesic effect of TENS on ocular pain.
Methods: In our prospective pilot study, participants with suspected NOP were randomized to an active or sham forehead TENS treatment for a 6-month period. During the first in-lab trial, all participants underwent a 20-minute treatment with their assigned device and the intensity of current ocular pain was queried before treatment and at 5-, 30-, 60-, and 120-minutes post- treatment. The patients were then instructed to use their device a few times throughout the week. At the 6-month time point, individuals were unmasked. Of the 42 subjects enrolled in our ongoing study, 29 have been unmasked, 20 of whom received the active device and 9 of whom received the sham device. For this study, we compared post-vs pre- TENS ocular pain intensity ratings (0-10 scale) at the initial in-lab trial in the active vs sham group. We used paired t-tests to examine change in pain report within each group and independent t-tests to examine differences between the two groups.
Results: The mean age of the 29 unmasked subjects was 57± 13 years, with the majority of subjects identified as female (55%, n=16). Pre-TENS, mean ocular pain intensities were 3.75 ± 2.85 in the active group and 5.00 ± 2.12 in the sham group (p=0.25). After a 20-minute treatment, pain intensity decreased by an average of 1.30, 2.06, 2.28, and 2.21 points at 5, 30, 60, and 120 minutes, respectively, in the active group (p<0.05 for all), and by an average of 2.44, 2.67, 2.44, and 2.56 points at the same time points in the sham group (p<0.05 for all). Mean pain intensities at 120 minutes post-TENS were 1.42±2.19 in the active group and 2.44±2.88 in the sham group (p=0.31).
Conclusions: A significant decrease in pain intensity was found in the active and sham TENS group at all four time points. Further studies are needed to assess mechanisms that underlie the clinical findings.
Candidate: Hueyjong Shih
Poster #: 30
Case Report of use of Compounded Losartan Drops to Minimize Corneal Scarring After a Full Thickness Corneal Laceration
Hueyjong Shih, Emma Davies
Purpose: The purpose of this study was to report our first clinical experience using topical losartan to minimize corneal scarring after traumatic full thickness corneal laceration.
Methods: Losartan is an angiotensin II receptor blocker that acts as an inhibitor of transforming growth factor-β. Animal studies have shown that topical losartan decreases stromal scarring fibrosis following Descemtorhexis in rabbits. The first human case of Losartan being used to treat corneal scarring occurred in a patient with corneal scarring fibrosis after LASIK surgery complicated by a free cap and severe diffuse lamellar keratitis. It has also been used in humans to treat severe corneal haze after epithelium-off corneal cross-linking. We report the case of a 40-year-old male who sustained a full thickness corneal laceration (Zone 1 open globe injury) due to penetration with a high-speed metallic foreign body while grinding metal. At presentation, the patient’s visual acuity (VA) was count fingers (CF) at face and exam showed an 8mm paracentral corneal laceration with lens violation and anterior lens capsule rupture. He required an open globe repair with lensectomy and anterior vitrectomy. At the time of presentation to cornea clinic, it had been 10 months since his open globe operation. He reported ghosting, “frosty” vision, and persistent monocular diplopia. Corneal topography showed extensive irregular astigmatism from corneal scarring and slit lamp exam revealed full thickness stromal whitening. The patient was hesitant to pursue full thickness corneal transplant and elected to proceed with off-label use of topical losartan 6 times daily to improve his corneal scar.
Results: The patient returned to clinic 5 months later with significant improvement in corneal scarring; exam showed faded stromal whitening surrounding his previous irregular full thickness corneal laceration (Figures 1-3). His BCVA was 20/25. In addition, Kmax on corneal topography decreased from 57.8D to 55.9D. He was continued on a repeat course of losartan 6 times daily in the left eye to determine if any more improvement could be achieved. At the most recent visit, 2 years from the original injury, he requested a third trial of losartan given his level of improvement from previous trials.
Conclusions: Our clinical experience highlights topical losartan as a promising novel therapeutic option for significant corneal scarring following a full thickness corneal laceration injury secondary to high-speed penetrating trauma resulting in a Zone 1 open globe injury. Further clinical studies are needed to identify optimal treatment dosages, durations, and other corneal insults which may have a course of healing that is positively impacted with the use of topical losartan.
Candidate: Shweta Suiwal
Poster #: 31
Ritanserin and Duloxetine as Treatment Options for Aniridia
Associated Keratopathy (AAK) – Gene Expression Study in Primary Limbal Epithelial Cells, In Vitro
Shweta Suiwal, Mahsa Nastaran Pour, Fabian Norbert Fries, Li Zhen, Ning Chai, Berthold Seitz, Maryam Amini, Tanja Stachon, Nóra Szentmáry
Purpose: In congenital aniridia, in case of PAX6 haploinsufficiency, chronic progressive limbal epithelial stem cell insufficiency and corneal conjunctivalization is observed, which is called aniridia-associated keratopathy (AAK). Due to the low number of aniridia patients, the availability of primary aniridia limbal epithelial cells to develop new therapeutic options is limited. The antipsychotropic drug duloxetine and a potent serotonin 2A receptor antagonist, ritanserin increased PAX6 expression in aniridia-like CRISPR/Cas9 genome edited corneal epithelial cells by inhibiting the MEK\ERK signaling pathway. Our purpose was to investigate the effect of ritanserin and duloxetine on gene expression of PAX6 and target genes (K12, K3, DSG1, ALDH1A1, ADH7, FABP5, ABCG2, SPINK7) in healthy primary limbal epithelial cell cultures (pLECs), aniridia patient’s pLECs culture, small interfering RNA (siRNA) based primary aniridia cell model, with PAX6 gene knockdown, in undifferentiated and differentiated primary limbal epithelial cell cultures.
Methods: Primary LECs were isolated from corneoscleral rims of healthy donors and cultured in serum free keratinocyte growth medium (KGM3). The treatment of 5 µM ritanserin and duloxetine has been performed for 24 hours on healthy pLECs culture and aniridia pLECs cultures. For siRNA knockdown, 48 hrs transfection (PAX6 knockdown) has been performed prior to the drug treatment. For differentiation of pLECs, 0.9mM calcium supplemented KGM3 medium was used. PAX6, K12, K3, DSG1, ALDH1A1, ADH7, FABP5, ABCG2, SPINK7 gene expression of the pLECs has been analyzed by qRT-PCR and western blot.
Results: Duloxetine inhibits the expression of phosphorylated kinases (pERK) nevertheless, did not significantly enhance the expression of PAX6. Ritanserin did not have significant effect on pERK and PAX6 expression in healthy and in anridia patient’s pLECs cultures. The expression of PAX6 remained unaltered in undifferentiated and differentiated aniridia cell model cultures upon duloxetine and ritanserin treatment. The expression of PAX6 related target genes also did not alter after the addition of duloxetine and ritanserin.
Conclusions: In healthy and PAX6 deficient aniridia primary limbal epithelial cells, ritaserin and duloxetine have no significant effect on PAX6 expression. The aniridia cell model (PAX6 knockdown) in undifferentiated and differentiated state did not show any significant alterations in expression of PAX6, cornea specific keratin K12 and K3, adhesion protein DSG1, retinoic acid signaling components ALDH1A1, ADH7 and FABP5, stem cell marker ABCG2 and proteases marker SPINK7.
Candidate: Rachel Tandias
Poster #: 32
Concurrent Limbal Stem Cell Deficiency and Neurotrophic Keratopathy in Graft-Versus-Host Disease
Leyla Yavuz Saricay, Pier Luigi Surico, Rachel Tandias, Ula V. Jurkunas, Reza Dana
Purpose: To explore the concurrence of limbal stem cell deficiency (LSCD) and neurotrophic keratopathy (NK) in patients with ocular graft-versus-host disease (GVHD).
Methods: Medical records of patients with ocular GVHD were retrospectively reviewed. Parameters collected included corneal sensitivity measured via non-contact esthesiometer, corneal fluorescein staining score (CFS, NEI grading scale), and tear volume (Schirmer-I test). Corneal nerve density, epithelial dendritic cell density, and limbal anatomy were assessed by in-vivo confocal microscopy (IVCM).
Results: Among 28 patients with ocular GVHD, 50% (n=14) had partial LSCD, and 32% (n=9) had complete LSCD. Corneal sensitivity was reduced (sensitivity threshold >4 mbar) in 27 patients (96%). IVCM analysis revealed a reduced mean total nerve density of 8059±3469 mm/mm2 and an increased mean dendritic cell density of 17.5±16.9 cells/mm2. Mean CFS score was 7.0±3.7, and mean Schirmer's test value was 8.0±7.5 mm/5 min. Corneal total nerve density (p=0.006), dendritic cell density (p=0.04), and corneal sensation (p=0.02) were significantly reduced in patients with complete LSCD compared to those with no LSCD.
Conclusions: Nearly all patients with ocular GVHD showed reduced corneal nerve density and corneal sensation, suggesting a diagnosis of NK. Most also had partial or complete LSCD. The high concurrence of these disorders suggests a compelling potential pathophysiological link.
Candidate: Bernd Vanmeerhaeghe
Poster #: 33
Corneal Endothelial Cell Transfection by Photoporation of a Photosensitizer Loaded Hyaluronic Acid Gel
Bernd Vanmeerhaeghe, Kevin Braeckmans, Dimitri Roels, Stefaan De Smedt, Félix Sauvage
Purpose: Current treatment of corneal endothelial diseases (e.g. Fuch’s dystrophy) is limited to corneal transplantation which suffers from a low number of available qualitative grafts, limiting the number of patients that can be treated. New pharmacological alternatives, e.g. nucleic acids (NA) inhibiting the Rho kinase pathway, which could stimulate the proliferation of corneal endothelial cells (CEC), are of current interest. However, selectively delivering NA to CEC is challenging due to several corneal barriers and lysosomal degradation of NA. Using in vitro and ex vivo models, we investigated whether photoporation, a technique creating transient pores in cell membranes by imploding vapor nanobubbles (VNB’s) originating from pulsed laser light irradiation of photosensitizers, overcomes these barriers and facilitates NA transfection. Additionally, embedding NA together with photosensitizers, i.e. gold nanoparticles (AUNPs), in a ready-to-use hyaluronic acid (HA) gel, commonly used to protect CEC during cataract surgery, was investigated to improve applicability and reduce tissue accumulation of AUNP after photoporation.
Methods: Immortalized human CEC (HCEC-B4G12), bovine corneas and human corneal explants were used as in vitro and ex vivo models to study delivery and transfection efficiencies of FITC-dextran (FD) 150, FD 500, siRNA and eGFP mRNA to CEC. AUNPs with a size of 100 nm were irradiated by a 561 nm pulsed laser (<7ns; 1.6 J/cm²) to generate VNB’s. These particles were also embedded in a HA (1000-2000 kDa) gel. Optimization was performed in vitro by investigating transfection efficiency and viability by flow cytometry and CellTiterGLo assay respectively. Residual gold after photoporation was determined using ICP-MS. Microscopy was used to detect ex vivo transfection and two functional CEC markers on both models with the optimized conditions.
Results: In vitro FD delivery resulted in optimal transfection using 32*10^7 AUNP/mL for non-embedded AUNPs, while HA embedded AUNPs showed most optimal transfection at 512*10^7 AUNPs/mL. These conditions were used for ex vivo FD 150 and 500 delivery in bovine CEC’s while FD 150, FD 500, anti P-16 siRNA and eGFP mRNA delivery was successful in human CEC’s. Embedding AUNPs in HA gel results in reduced intracellular gold after photoporation while functional CEC markers show no difference between non treated and photoporated CEC’s.
Conclusions: Using in vitro optimized photoporation conditions it was feasible to deliver NA to ex vivo human CEC’s, even when AUNPs were embedded inside a HA gel. Embedding AUNPs in a HA gel resulted in reduced intracellular amount of gold after treatment while CEC functionality remains unaltered.
Candidate: Joanna Wasielica-Poslednik
Poster #: 34
Management of Postoperative Intraocular Pressure Elevation After DMEK
Anna L. Engel, Lena Elbert, Stephanie Grabitz, Adrian Gericke, Norbert Pfeiffer, Joanna Wasielica-Poslednik
Purpose: Descemet membrane endothelial keratoplasty (DMEK) is a highly effective surgical treatment for patients suffering from dysfunctional corneal endothelium. This study aimed to analyze the incidence and risk factors for early intraocular pressure (IOP) elevation following DMEK. Additionally, the study examined the frequency, types, and outcomes of IOP-lowering interventions performed in the patient cohort.
Methods: In this retrospective study, patients who underwent DMEK from January 2020 to December 2022 at a single university eye clinic were included. The primary outcome measures were IOP, intracameral gas fill, and IOP-lowering interventions assessed at the first clinical slit-lamp examination three hours postoperatively, as well as during the following two days.
Results: The study included 358 eyes of 263 patients, with an average age of 73.7 ± 11.2 years, of which 55.3% were women. The indications for DMEK were Fuchs corneal endothelial dystrophy (64%), pseudophakic bullous keratopathy (23%), and other reasons (13%). An IOP-lowering intervention was performed in 64 of the 358 eyes (17.9%) at the three-hour follow-up. Specifically, reduction of intracameral gas fill via venting was performed in 29 eyes (n=8.1%) while systemic acetazolamide was administered in 40 eyes (11.1%). Six eyes required more than one intervention. Both venting and medication effectively normalized IOP within the first day after DMEK in all cases.
Conclusions: Standardized clinical examinations three hours after DMEK enable the early identification and treatment of raised IOP. Both reduction of intracameral gas fill and systemic acetazolamide administration effectively normalized IOP. However, these interventions should not be used interchangeably as the presence or absence of a pupillary block necessitates different approaches.
Candidate: Qingguo Xu
Poster #: 35
Nanomedicine Strategy for Treating High Risk Corneal Transplantation Rejection
Tuo Meng, Jinhua Zheng, Crystal Shin, Ghanashyam Acharya, Qingguo Xu
Purpose: High-risk corneal transplantation presents a formidable challenge, with over 50% grafts experiencing rejection despite intensive postoperative care involving very frequent topical eyedrop administration up to every two hours, gradually tapering over 6~12 months, and ongoing maintenance dosing. Effective anti-angiogenesis is important for managing high risk corneal transplantation rejection. Here, we engineered controlled release nanomedicine formulations comprising immunosuppressants via nanoparticles and anti-angiogenesis drugs via nanowafer, and evaluated the efficacy of the combination of nanoparticles and nanowafers for preventing high-risk graft rejection in a clinically-relevant rat model.
Methods: Dexamethasone sodium phosphate (DSP) loaded PLA-2COOH NP (PLA DSP-NP) were prepared by nanoprecipitation method, and PLA DSP-NP were shown to provide 6 months DSP release in rat eyes following a single subconjunctival (SCT) injection. The Axitinib loaded nanowafer (Axi NW) was fabricated using PVA polymer and containing arrays of 500 nm square drug reservoirs filled with Axi. The topical application of Axi NW was shown to enhance the drug retention and absorbtion on the ocular surface. To construct the HR PKP model, the corneal neovascularization was first developed by placing 3 intrastromal nylon sutures on Lewis rat’s cornea and the sutures were removed in 2 weeks. The high -risk corneal allograft transplantation was conducted at 3 weeks after suture removal when the active corneal NV was silenced. The PKP surgeries were performed by transplanting a 3.5 mm central corneal button from donor Fischer rats to the recipient Lewis rats. Immediately after the HR PKP surgery, the HR PKP eyes were given a single SCT injection of PLA DSP-NP (400µg DSP). Starting at POD3, the topical administration of Axi NW (10 µg Axi) was given once every other day for 7 times. The untreated group, or the monotherapy of either SCT injection of PLA DSP-NP (400µg DSP) only and topical Axi NW (10 µg Axi) only was used as control. N=5-8 for each group. The treated eyes were observed for clinical scores over 6 months in terms of corneal edema, neovascularization and opacity. Grafts were considered to have been rejected when the total score reached 5 with opacity score ≥3.
Results: We successfully developed the rat high-risk cornea transplantation rejection model to mimic the clinical setting that the PKP surgery was performed on the non-inflamed corneal bed with silenced or partially silenced corneal NV. Unlike untreated corneal grafts, which universally faced rejection within 2 weeks post-surgery, a single SCT injection of the long-acting immunosuppressant nanoparticle (PLA DSPNP) alone effectively averted graft rejection for 6 months achieving a graft survival rate of ~70%. Notably, the combination of immunosuppressant nanoparticle (PLA DSP-NP) and anti-VEGF nanowafer (Axi NW) yielded significantly better efficacy with a graft survival rate of >85%.
Conclusions: Both the single dosing of the PLA DSP-NP and the combination treatment of PLA DSP-NP with Axi NW successfully prevented the rat high-risk corneal transplantation rejection for 6 months. The sustained and enhanced delivery of corticosteroid and anti-angiogenesis therapies using the long-acting formulations provided promising treatment strategies for preventing high-risk corneal transplantation rejection with improved safety profiles and increased patient compliances, while without needing the tedious eyedrop dosing.
Candidate: Gink Yang
Poster #: 36
Can FGF7 be a Therapeutic Target for Fuchs Endothelial Corneal Dystrophy?
Gink N. Yang, Yu B. Y. Sun, Hothri Moka, Min K. Sung, Geraint J. Parfitt, Kathryn Davidson, Karl D. Brown, Greg J. Dusting, Jose M. Polo, Mark Daniell
Purpose: Fuchs Endothelial Corneal Dystrophy (FECD), a blinding disease remains the most common indication for corneal transplantation in high-income nations. To develop less invasive therapies and reduce the need for surgery for early symptomatic patients, Next Generation Sequencing has been used to reveal a range of therapeutic targets. Our latest snRNA-sequencing study investigated the spatial expression of FECD-related genes at a single cells level using FECD patient endothelium and healthy human endothelium as control. This study aimed to compare the genetic signatures between the diseased versus control to reveal key therapeutic targets for pharmaceutical development.
Methods: Healthy cadaveric donors with an average corneal endothelial cell count above 2500mm2 were recruited from Victoria, Australia. Individuals were excluded if the post-mortem time was longer than 12 hours, or they had a history of eye disease, infections, autoimmune disease, inflammatory disease or metabolic disorders. Living participants with FECD symptoms including pseudophakic bullous keratopathy and corneal decompensation were recruited to the study. Diseased corneal endothelium from patients was collected as surgical discard and snap-frozen in liquid nitrogen. Nuclei were isolated from the endothelium of the diseased and control samples. Isolated nuclei were enriched using fluorescence-activated cell sorting. Nuclei from H9ES and K562 cells were used as ‘spike-in’ sequencing quality control. Complimentary DNA library was constructed using the Chromium Single Cell 3’ Reagent Kit. Sequencing was carried out on Illumina NovaSeq 6000 using a paired-end 2x150bp sequencing strategy. hg19 genome was used to align the results to known genes. Samples with reads mapped to less than 90% to hg19 genome were considered a failed sequencing. Decluttering of FASTQ file was performed using unique molecular identifier (UMI) counting in Cellranger program (v.3.0.2) against Ensemble’s GRCh37 annotation. Integration analysis was carried out by the R package “Harmony”. Corneal endothelial cells were further annotated according to the expression of function-specific and membrane-specific CEC genes suggested by previous studies.
Results: Two out of three samples from each cohort were found to be successful sequencing. Given that less than three sets of data were derived from the experiments, the results were regarded as case studies. Seven distinctive cells clusters were identified using FECD-related genes as a clustering tool in the FECD samples. ALCAM, CA12, CACANA1A, CACNB4, COL4A3, COL8A1, COL8A2, DLG1, IER3, LAMB1, NCAM1, PCSK7, PTGDS, SLC20A11, SLC5A3 and SYNE2 were differentially expressed in these seven cell clusters. Specifically, the expression of fibroblast growth factor 7 (FGF7) was found to be 2-fold higher in more than 80% of cells in FECD endothelium compared to healthy controls. Consistently, the number of cells expressing FGF7 receptors including FGFR1 and FGFR2 is highly elevated in FECD endothelium compared to healthy controls.
Conclusions: Single cell RNA-sequencing is an effective tool at identifying distinct genetic signatures in FECD patient samples. Given that corneal endothelial cells go through mesenchymal transition during FECD disease progression, and FGF7 is known to exert its paracrine effect on cell differentiation via FGFR1 and FGFR2, reducing the expression of FGF7 may be beneficial at slowing down the progression of FECD.
Candidate: Leyla Yavuz Saricay
Poster #: 37
1-Year Changes in the Central Cornea on Anterior Segment OCT and In Vivo Confocal Microscopy in
Leyla Yavuz Saricay, Aaron R. Kaufman, Lynette K. Johns, Jia Yin, Lassana Samarakoon, Nidal Chowdhury, Allison R. Ayala, Maureen Maguire, Mohit Parekh, Diego E. Hernandez Rodriguez, Heather Daley, Reza Dana, Myriam Armant, Jerome Ritz, Ula V. Jurkunas
Purpose: To describe 1-year changes in the cornea as assessed by anterior segment optic coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM) for participants receiving a tissue graft generated from a new manufacturing process utilizing cultivated autologous limbal epithelial cells (CALEC).
Methods: Fourteen participants with unilateral limbal stem cell deficiency (LSCD) were enrolled at a single clinical center. Cellular grafts were produced in a two-stage manufacturing process following a GMPcompliant protocol. AS-OCT and IVCM were completed at baseline and 12 months after the treatment in subsets of these participants. Efficacy outcomes were determined based on improvement in central corneal epithelial basal cell density (EBCD), change in central corneal epithelial thickness (CET), and presence of conjunctival or corneal cells in central cornea.
Results: Among 14 participants, thirteen (93%) were male, 12 (86%) were white, the mean age at enrollment was 46±16 years, 11 (79%) had level III LSCD severity, and 10 (71%) had no epithelial defects at baseline. At baseline, the median BCVA was 1.91 [range: 0.30, 2.90] LogMAR, CET was 53 [range: 34, 64] microns, EBCD was 3964 [range: 822, 5788] cells/mm2; the central cornea contained corneal epithelial cells in 20% and conjunctival epithelial cells in in 90%. At 12 months postoperatively, the mean changes were -0.61 LogMAR in BCVA [P=0.06], 3 microns in CET [P=0.67], 1967 cells/mm2 in EBCD [P=0.02]; the proportion with central corneal epithelial cells increased to 75% and the proportion with conjunctival epithelial cells decreased to 38%.
Conclusions: The findings from AS-OCT and IVCM are consistent with the observed clinical enhancements in participants with LSCD treated with CALEC, likely attributable to the amelioration of corneal pannus and the optic axis becoming clear. Nevertheless, IVCM is notably more effective for in-depth analysis of the epithelial phenotype and thickness. Furthermore, these findings significantly bolster the proposition of cellular therapy products as a treatment alternative for individuals with LSCD
Candidate: Haozhe Yu
Poster #: 38
Tear Lipid Peroxidation Products as new Potential Biomarkers for Dry Eye Disease Diagnosis
Purpose: To investigate the diagnostic value of tear levels of lipid peroxidation products 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) in dry eye disease (DED).
Methods: Seventy-six suspected DED subjects who first visited the ophthalmology department were consecutively recruited. Before further diagnosis, their tears were collected and analyzed through enzymelinked immunosorbent assay to determine the level of 4-HNE and MDA. The diagnostic performance of tear 4-HNE and MDA level was assessed using area under curve (AUC), and their correlation with DED symptoms and signs was explored. Another 8 DED patients and 8 healthy subjects were recruited to repeat measure their tear 4-HNE and MDA levels at 9:00 am, 3:00 pm and 9:00 am the following day to evaluate inter-day and intra-day expression stability using Bland-Altman analysis and coefficient of variation (CV).
Results: The tear levels of 4-HNE and MDA in the DED group were higher than those in the non-DED group (P<0.001). The AUC values for tear 4-HNE and MDA levels in diagnosing DED were 0.800 (P<0.001) and 0.740 (P<0.001), respectively. Their level in tears also showed good correlation with subjective symptoms, ocular surface status, corneal nerve morphology, and meibomian gland function in patients with DED. The intraday-to-interday variation in tear 4-HNE and MDA levels was less than 1.2-fold with a CV less than 10% in the vast majority of both DED and healthy subjects.
Conclusions: Tear 4-HNE and MDA are effective diagnostic biomarkers for DED with a significant correlation with symptoms and signs and stable expression.
Candidate: Sarah Zwingelberg
Poster #: 39
The Influence of Obesity, Diabetes Mellitus and Smoking on Fuchs Endothelial Corneal Dystrophy (FECD)
Sarah B. Zwingelberg, Barbara Lautwein, Till Baar, Monika Heinzel-Gutenbrunner, Melanie von Brandenstein, Simiak Nobacht, Mario Matthaei, Björn O. Bachmann
Purpose: To detect environmental factors, which may be possible risk factors in the disease course of Fuchs’ endothelial corneal dystrophy (FECD).
Methods: Evaluation of patients with FECD registered in the FECD genetics database of the Center for Ophthalmology, University Hospital Cologne. For the evaluation, disease onset, central corneal thickness (CCT), best spectacle corrected visual acuity (BSCVA, logMAR), and modified Krachmer grading (grades 1-6) were correlated with the presence of diabetes mellitus (DM), body mass index (BMI), and smoking behavior. To put the age-related increase in Krachmer grading into perspective, a correction of grading were formed. Depending on the variables studied, differences between groups were examined by Mann-Whitney U test and chi-square test. The significance level was 5%.
Results: 403 patients with FECD were included in the analysis. The mean age of the patients was 70.0 ±10.32 (range 28-96) years. The mean age at diagnosis of those patients was 63.1 ±13.2 years. The femaleto-male ratio was 1.46:1. Patients with a BMI > 30.0 kg/m² developed FECD significantly earlier than patients with a BMI < 30 kg/m²,p = 0.001. Patients with DM showed significantly more often an Krachmer grade of 5, p = 0.015. Smoking had a negative effect on Krachmer grading (p = 0.024). Using the mediation analysis, the presence of DM correlated Krachmer Grade 5 (p = 0.015), and the presence of DM correlated with BMI > 30.0 kg/m2 (p = 0.012).
Conclusions: In addition to smoking and DM our study shows for the first time that obesity may have a negative impact on the development of FECD. Whether dietary interventions and hormones can influence the development or progression of the disease needs to be investigated in future studies.
