Research and Publications
Current Research & Scholarly Interests
Thyroid Eye Disease (Video: TEPEZZA® - FDA-Approved Treatment)
Adenoid Cystic Carcinoma of the Lacrimal Gland
Lacrimal Gland Stimulation for the Treatment of Dry Eyes
Neurostimulation
Orbital Tumors
Floppy Eyelid Syndrome and Obstructive Sleep Apnea
View more information about our Thyroid Eye Disease Clinical Trials in our pamphlet or in the trial details below.
1. A phase 3b/4 double masked, randomized clinical trials to evaluate the safety, efficacy and tolerability of different dosing duration of Teprotumumab
Status: Active
Research Coordinator: Farheen (fqshaikh@stanford.edu)
For eligibility and more information, please see NCT05002998.
Background: This is a double-masked, randomized, parallel-assignment, multicenter trial examining the safety and tolerability of teprotumumab in the treatment of Thyroid Eye Disease (TED) in adult participants. This international, Phase 3b/4 trial is being conducted to fulfill an FDA post-marketing requirement for a descriptive trial to evaluate the safety, efficacy and need for re-treatment of 3 different teprotumumab treatment durations for TED. In addition, serum samples from participants with a Baseline Clinical Activity Score (CAS) ≥3 will be evaluated for biomarkers of disease.
2. A Phase 2b, Randomized, Double-Mask, Placebo Controlled, Study to Evaluate the Safety, Pharmacokinetics and Efficacy of Oral Linsitinib in Subjects with Active, Moderate to Severe Thyroid Eye Disease
Status: Active
Co-PI: Chrysoula Dosiou, MD, MS
Research Coordinator: Farheen (fqshaikh@stanford.edu)
For eligibility and more information, please see NCT05276063.
Background: The overall objective is to study the safety, pharmacokinetics and efficacy of linsitinib (a small molecule IGF-1R inhibitor) administered orally twice daily (BID) vs. placebo, at 24 weeks in the treatment of subjects with active, moderate to severe thyroid eye disease (TED).
3. Evaluate the safety, tolerability and Efficacy of VRDN-001, a monoclonal antibody in patients with Thyroid Eye disease
Status: Active
Research Coordinator: Farheen (fqshaikh@stanford.edu)
For eligibility and more information, please see NCT05176639.
Background: The investigational drug, VRDN-001, is a monoclonal antibody that inhibits the activity of a cell surface receptor called insulin-like growth factor-1 receptor (IGF-1R). Inhibition of IGF-1R may help to reduce the inflammation and associated tissue swelling that occurs in patients with thyroid eye disease (TED). This clinical trial will evaluate the safety, tolerability and pharmacokinetics (the concentration of drug in the blood over time) of VRDN-001 in healthy volunteers and in patients with TED. Study participants with TED will also be evaluated over time for changes in their signs and symptoms of TED compared to their baseline measurements.
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The Secondary Beneficial Effects of Prostaglandin Analog Treatment in Thyroid Eye Disease Patients.
The purpose of this study is to evaluate the potential secondary beneficial effect of prostaglandin analogues (PA) treatment in thyroid eye disease (TED) patients. This study aims to determine if PA would change the course of the orbitopathy in TED patients by altering the progression of the common features of TED, including fatty hypertrophy, proptosis, eyelid retraction and optic nerve compression. The eyes with thyroid eye disease and elevated intraocular pressure will be randomised to the PA treatment and the other eye will serve as a control eye and will be treated with Timolol.
Investigator
Not accepting patients at this time View Details -
Surgical Idiopathic Intracranial Hypertension Treatment Trial
Randomized trial of adults (≥18 years old) with idiopathic intracranial hypertension and moderate to severe visual loss without substantial recent treatment who are randomly assigned to (1) medical therapy, (2) medical therapy plus ONSF, or (3) medical therapy plus VPS. The primary outcome is visual field mean deviation change at first of Month 6 (26 weeks) or time of treatment failure of the eligible eye(s), followed by a continuation study to assess time to treatment failure. The determination of eligible eye(s) is based on meeting the eligibility criteria at baseline.
Investigators
Not accepting patients at this time View Details
Publications
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Why Metrics Matter in Thyroid Eye Disease: An Innovate TED Initiative.
JAMA ophthalmology
Kazim, M., Baldeshi, L., Cruz, A. A., Dolman, P. J., Dosiou, C., Eckstein, A., Kikkawa, D., Kossler, A. L., Mawn, L. A., Singh Ospina, N., Perros, P., Rootman, D. B., Salvi, M., Stan, M. N., Sullivan, T. J., Wester, S. T.
2026
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Abstract
Advances in the understanding of the pathophysiology of thyroid eye disease (TED) provide an opportunity to use novel, targeted therapeutic agents. However, our capacity to assess the efficacy and indications for the new agents is potentially limited by the clinical metrics used in recent research trials, which fail to adequately capture the clinical complexity and diversity of TED.To review the features of TED that make it atypical among autoimmune diseases, review the limitations of the currently available metrics, and introduce the Innovate TED Initiative to develop new outcome metrics.To best evaluate and use potential new therapeutic agents for TED, physicians with expertise in the field perceive the need for a novel set of metrics. The outlined Innovate TED Initiative can, through the design and execution of prospective validation studies, develop the requisite metrics for the mutual benefit of physicians, regulatory bodies, the pharmaceutical industry, and patients with TED.
View details for DOI 10.1001/jamaophthalmol.2026.3823
View details for PubMedID 42720935
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WSOPRAS and ITEDS Consensus Statement on the Assessment and Management of Thyroid Eye Disease.
Ophthalmic plastic and reconstructive surgery
Kossler, A. L., Grover, A. K., Cruz, A. A., Baldeschi, L., Kazim, M., Sullivan, T. J.
2026
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Abstract
To develop a globally applicable consensus statement for the assessment and management of thyroid eye disease (TED).The World Society of Ophthalmic Plastic Reconstructive and Aesthetic Surgery council selected a 6-member, geographically diverse TED task force to develop a consensus statement on the assessment and management of TED. Consensus was achieved through monthly meetings from January to July 2025, alongside an analysis of the literature in terms of relevance, level of evidence, and global versus local applicability. A draft document was circulated to all World Society of Ophthalmic Plastic Reconstructive and Aesthetic Surgery constituent societies for feedback. Using a modified Delphi approach, the expert panel convened over 6 additional virtual sessions from July 2025 to March 2026 to review the submitted feedback, incorporating comments with agreement from at least 5 of 6 experts. The final statement was approved by both the World Society of Ophthalmic Plastic Reconstructive and Aesthetic Surgery council and the International Thyroid Eye Disease Society board of directors.Consensus was achieved regarding methods, TED definitions, assessment, medical and surgical management, and safety recommendations. The consensus statement delineates acceptable standards, workup, and evaluation time points for basic-, intermediate-, and advanced-level assessment tailored to diverse global contexts, as well as tiered medical and surgical interventions, recommended for the different phases and severities of TED.The World Society of Ophthalmic Plastic Reconstructive and Aesthetic Surgery-International Thyroid Eye Disease Society consensus statement on TED, developed by oculoplastic and orbital surgeons, provides a global framework for the standardized assessment and management of TED to improve TED care and enhance patient outcomes.
View details for DOI 10.1097/IOP.0000000000003277
View details for PubMedID 42684865
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Paired longitudinal tear proteomics reveals persistent ocular surface dysregulation after teprotumumab therapy in thyroid eye disease.
Communications medicine
Velez, G., Ngo, G. H., Young, D., Amarikwa, L., Dufour, A., Kossler, A. L., Mahajan, V. B.
2026
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Abstract
Thyroid eye disease (TED) is a complex autoimmune disorder that is frequently disfiguring and sight-threatening. Recent advances have shifted treatment from surgery toward targeted biologic therapies like teprotumumab (TMB), an IGF-1R inhibitor that improves proptosis, diplopia, and inflammation. However, ocular surface symptoms often persist.We conducted a longitudinal pre-post comparative study of patients with active, moderate-to-severe TED treated with TMB at a tertiary academic medical center, with tear sampling at two prespecified time points: baseline (collected within the 3 weeks strictly antecedent to the first infusion) and post-treatment (within 6 months of the final infusion). Adults with active, moderate-to-severe TED who received ≥4 TMB infusions were eligible. All patients contributed paired pre- and post-treatment tear samples (22 eyes). Controls were adults without TED or ocular surface disease (32 eyes). Tear fluid was collected by Schirmer strips and analyzed by liquid chromatography-tandem mass spectrometry. Differential expression was assessed using a linear mixed-effects model to explicitly account for the intrinsic correlation between paired eyes; correlations between LFQ intensities and clinical metrics used Spearman rank correlation.A total of 2974 proteins were identified across 76 tear samples. Unsupervised analyses demonstrated separation between control, pre-treatment, and post-treatment TED tear proteomes. Although TMB induced substantial proteomic changes, post-treatment profiles did not revert to a control-like state. Proteins involved in inflammation, oxidative stress, and cytoskeletal organization remained persistently dysregulated, while a subset of tear film stability-associated proteins normalized. Several persistently dysregulated protein targets overlapped with FDA-approved drugs.These observational findings support tear proteomics as a platform for biomarker discovery and therapeutic prioritization and warrant validation in larger, independent cohorts.
View details for DOI 10.1038/s43856-026-01757-6
View details for PubMedID 42380591
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A Novel Trans-Orbital Surgical Procurement Technique for Human Whole Eye Transplant
Pakdel, F., Kossler, A. L., Nguyen, D., Kinde, B., Kim, T., Dong, X., Pirmarzdashti, N., Mamchik, V., Tadevosyan, E., Goldberg, J. L.
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2026
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View details for Web of Science ID 001878001900036
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THRIVE: A Phase 3, Randomized, Double-Masked, Placebo-Controlled Study of Veligrotug for Active Thyroid Eye Disease.
Ophthalmology
Yen, M. T., Cockerham, K., Saeed, P., Leibowitz, S., Mudumbai, R. C., Schittkowski, M. P., Lee, V., Abrams, J., Turbin, R. E., Pío-Rendón, J. B., Bertelmann, E., Eade, E., Nijhawan, N., Pérez-López, M., Sales-Sanz, M., Zhang-Nunes, S., Kossler, A. L., Pajak, A., Narvekar, A., Tripuraneni, R., Garrido-Hermosilla, A. M.
2026
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Abstract
Thyroid eye disease (TED) is a debilitating autoimmune disease with significant unmet needs. This study's objective was to assess the efficacy and safety of veligrotug, a full antagonist monoclonal antibody to the insulin-like growth factor-1 receptor, in patients with active TED.Veligrotug was assessed in THRIVE, a global, multicenter, randomized, double-masked, placebo-controlled phase 3 trial.Adult patients with moderate-to-severe active TED (onset ≤ 15 months, proptosis ≥ 3 mm above normal, and clinical activity score [CAS] ≥ 3) received either veligrotug or placebo.Patients were randomized 2:1 to receive 10 mg/kg veligrotug or placebo administered every 3 weeks for a total of 5 IV infusions.The primary end point at week 15 was the proptosis responder rate (PRR; ≥ 2-mm reduction by Hertel exophthalmometry) or overall responder rate (ORR; PRR and ≥ 2-point reduction in CAS), depending on geographic region. Efficacy and safety were assessed through week 52.A total of 113 patients received veligrotug (n = 75) or placebo (n = 38). Baseline characteristics were balanced between the 2 arms. Improvements were observed at week 3, with a significantly greater response at week 15 for veligrotug versus placebo (P < 0.001) across all primary and secondary end points including: PRR by Hertel, 70% versus 5%; PRR by magnetic resonance imaging (MRI) or computed tomography (CT), 71% versus 9%; ORR, 67% versus 5%; mean proptosis reduction, 2.90 mm versus 0.48 mm (Hertel) and 2.96 mm versus 0.58 mm (MRI/CT); diplopia improvement, 59% versus 20%; and diplopia resolution, 49% versus 12%. At week 52, 70% of initial responders maintained proptosis response. Veligrotug was generally well tolerated, with a 4% treatment discontinuation rate. Most adverse events were mild and resolved, with no serious treatment-related adverse events and no changes in the safety profile through week 52.A 5-infusion course of veligrotug administered over 12 weeks was generally well tolerated and led to rapid and significant improvements in diplopia, proptosis, and disease activity, with a durable response through week 52. Veligrotug may become a promising new treatment option for active TED.Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
View details for DOI 10.1016/j.ophtha.2026.04.022
View details for PubMedID 42223386
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IL-11 receptor is a novel target for drug development with pharmacological activity in fibro-inflammatory disease.
Scientific reports
King, D. J., Swaney, J. S., Rich, C., Jun, H. T., Vasquez, Y., Geller, S., Chidester, C., Chai, M., Elliott, E., Witherden, D., Hershoff, H., Kafi, A., Strauwald, A., Kossler, A. L., Silkiss, R. Z., Oester, A., Garrido-Hermosilla, A. M., Malik, M., Kikkawa, D. O., Fardis, M.
2026
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Abstract
IL-11, a novel target for drug development, has been associated with several fibroinflammatory diseases including thyroid eye disease (TED), where it plays an important role in signaling to stromal cells activating multiple intracellular pathways. In TED patient tissue, IL-11 is elevated and stimulates multiple effects important in disease progression, including the production of proinflammatory cytokines, hyaluronic acid (HA) and fibrotic markers. LASN01, a potent antibody to IL-11 receptor, inhibits these effects and is a potential therapeutic agent for TED. Teprotumumab, an antibody to IGF-1 receptor, inhibits HA production and adipogenesis and is effective in reduction of proptosis. Activation of the IGF-1 and IL-11 pathways in TED tissue induces the expression of fibroinflammatory genes regulated by LASN01 and lipid biosynthetic genes regulated by Teprotumumab. Clinical studies show that LASN01 is well tolerated and in a placebo-controlled phase II trial in TED, LASN01 resulted in a statistically significant resolution of clinical activity score (CAS) in 88% of treated patients (p = 0.028), but had lesser effects on proptosis. The data supports the importance of IL-11 biology in fibroinflammatory disease and that IL-11 receptor is a pharmacologically active target for drug development.
View details for DOI 10.1038/s41598-026-51600-0
View details for PubMedID 42069852
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Effect of Oral Opioid Prescription on Rates of Postoperative Pain among Ophthalmology Subspecialties: A Large Database Analysis
OPHTHALMOLOGY SCIENCE
Toth, A. B., Binczyk, N. M., Tran, E. M., Wai, K. M., Koo, E. B., Kossler, A. L., Rahimy, E., Mruthyunjaya, P., Koo, E. B.
2026; 6 (5): 101120
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To assess whether postoperative opioid prescriptions are associated with reduced pain diagnoses or emergency room (ER) visits after ophthalmic surgery.Retrospective cohort study using aggregated electronic health record data (June 2005-June 2025) from the TriNetX collaborative research network.Patients who underwent ophthalmic procedures across 11 subspecialty categories in the past 20 years, with or without a postoperative opioid prescription.Data were analyzed using the TriNetX integrated analytics platform. Patients with chronic pain syndrome or opioid dependence were excluded. Ophthalmic procedures were identified using Current Procedural Terminology codes, and characterized as cataract; major or minor cornea, glaucoma, oculoplastics, trauma; retina; or strabismus. Associations were assessed by calculating absolute risk differences with 95% confidence intervals (CIs) and risk ratios.Diagnosis of postprocedural pain or ER visits within 2 weeks after surgery.The study included 2 510 984 patients. Absolute rates of postoperative pain diagnoses were low across all subspecialties. Opioid prescriptions were associated with small absolute reductions in postprocedural pain diagnoses in glaucoma major (-1.3%, 95% CI: -1.4% to -1.2%, P < 0.001), oculoplastics major (-0.9%, 95% CI: -1.2% to 0.6%, P < 0.001), cornea major (-0.8%, 95% CI: -0.9% to -0.7%, P < 0.001), cornea minor (-0.8%, 95% CI: -0.8% to -0.7%, P < 0.001), trauma major (-0.8%, 95% CI: -0.9% to -0.6%, P < 0.001), trauma minor (-0.7%, 95% CI: -0.9% to -0.5%, P < 0.001), and oculoplastics minor (-0.1%, 95% CI: -0.2% to < -0.1%, P = 0.008) procedures. Emergency room visit reduction was observed only for glaucoma major procedures (-0.1%, 95% CI: -0.1% to < -0.1%, P < 0.001). In other subspecialties, opioid prescriptions were not associated with reduced ER utilization and were associated with higher ER visit rates in oculoplastics, retina, and trauma major procedures.Postoperative opioid prescriptions were associated with small absolute reductions in pain diagnoses in selected subspecialties, including cornea, glaucoma, oculoplastics, and trauma, but not cataract, retina, or strabismus. Opioid prescriptions offered no consistent benefit in reducing ER visits and were linked to higher ER visit rates in some subspecialties. These findings highlight the limited clinical benefit of routine opioid prescribing after many ophthalmic procedures and underscore the need for subspecialty-specific, evidence-based postoperative pain management strategies in ophthalmology.Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
View details for DOI 10.1016/j.xops.2026.101120
View details for Web of Science ID 001733468400001
View details for PubMedID 41958712
View details for PubMedCentralID PMC13059299
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The Role of Systemic Methotrexate on Preventing Proliferative Vitreoretinopathy Following Retinal Detachment Repair.
Ophthalmic surgery, lasers & imaging retina
Yavari, N., Alsoudi, A. F., Wai, K. M., Koo, E., Ludwig, C. A., Kossler, A. L., Mruthyunjaya, P., Rahimy, E.
2026; 57 (5): 320-326
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Abstract
This study aimed to evaluate the association between systemic methotrexate (MTX) use and the incidence of proliferative vitreoretinopathy (PVR) following retinal detachment (RD) repair.A retrospective cohort study was conducted using the TriNetX Health Research Network. Patients undergoing RD repair were identified by CPT codes and stratified into MTX users (systemic exposure within one year prior to or on the day of RD repair) versus nonusers. Cases of proliferative diabetic retinopathy were excluded. The primary endpoint was development of PVR-related complications within 3, 6, and 12 months postoperatively. Propensity score matching (PSM) was performed to balance baseline demographics and clinical covariates.After 1:1 PSM, 496 patients were identified in both cohorts (mean age: 56.5 (19.0) years). MTX use was associated with significantly higher odds of tractional RD at 3 months (22.38% vs 8.06%; odds ratio [OR] 3.28, 95% CI: 2.23-4.83, P < .0001), 6 months (24.95% vs 8.11%; OR 3.76, 95% CI: 2.57-5.52, P < .0001), and 12 months (20.29% vs 10.63%; OR 2.14, 95% CI: 1.44-3.17, P < .0001). Postoperative ERM development was more frequent in MTX cohort at 3 months (11.49% vs 6.65%, OR 1.82, 95% CI: 1.16-2.85, P = .0080). No significant differences were observed in complex RD repair, repeat PPV, and PPV with ERM removal.Systemic MTX use within one year of RD repair was not associated with a reduced risk of PVR. MTX exposure correlated with increased odds of tractional RD and higher rates of ERM development rate. These findings suggest systemic MTX may not offer protective benefit against PVR.
View details for DOI 10.3928/23258160-20260413-01
View details for PubMedID 42139590
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Xanthelasma and its association with developing major cardio-cerebrovascular events.
Atherosclerosis
Yavari, N., Wai, K. M., Alsoudi, A. F., Koo, E., Ludwig, C. A., Kossler, A. L., Mruthyunjaya, P., Rahimy, E.
2026; 416: 120647
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Abstract
To evaluate short- and long-term incidence of major adverse cardio-cerebrovascular events (MACCEs) in patients with xanthelasma.Using TriNetX, an aggregated electronic health-records network, we identified adults with xanthelasma and matched controls with presbyopia without xanthelasma. Patients with a history of myocardial infarction (MI), ST-elevation/non-ST-elevation MI, stroke, and transient ischemic attack (TIA) any time prior to diagnosis were excluded in both cohorts. Cohorts were matched 1:1 by propensity scores, and MACCEs were compared at 1-, 5-, and 10-years. A Kaplan-Meier was evaluated with the log-rank test based on the incidence of MACCEs.After PSM, there were a total of 17,925 patients with at least 12 months of follow-up in each cohort. At 1 year, xanthelasma was associated with higher incidence of MI (1.00% vs 0.35%; hazard ratio (HR) 2.92, 95% confidence interval (CI): 2.20, 3.90), stroke (0.95% vs 0.30%; HR 3.35, 95% CI: 2.44-4.52), and TIA (0.60% vs 0.19%; HR 3.29, 95% CI: 2.24, 4.84). At 5 years, MI (2.26% vs 1.13%; HR 2.24, 95% CI: 1.89, 2.65), stroke (2.25% vs 1.03%; HR 2.46, 95% CI: 2.06, 2.93), and TIA (1.60% vs 0.74%; HR 2.41, 95% CI: 1.96, 2.97) remained high. At 10 years, MI (3.13% vs 1.73%; HR 2.14, 95% CI: 1.85, 2.45), stroke (3.00% vs 1.53%; HR 2.32, 95% CI: 2.00, 2.70), and TIA (2.00% vs 1.13%; HR 2.10, 95% CI: 1.75, 2.50) remained elevated. All comparisons were statistically significant (p < 0.0001).Xanthelasma is associated with higher short- and long-term incidence of MACCEs up to 10 years, highlighting its value as a clinical marker for cardiocerebrovascular risk stratification and preventive management.
View details for DOI 10.1016/j.atherosclerosis.2026.120647
View details for PubMedID 42019468
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Risk of Retinal Redetachment After Cataract Surgery Following Retinal Detachment Repair in Myopic and Highly Myopic Eyes.
Journal of vitreoretinal diseases
Mesfin, Y., Arnal, L., Salvi, A., Wai, K. M., Brodie, F., Koo, E., Kossler, A. L., Koo, E., Rahimy, E., Mruthyunjaya, P., Ludwig, C. A.
2026: 24741264261418517
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Abstract
Purpose: To describe how risk factors such as repair of rhegmatogenous retinal detachment (RRD), cataract extraction, and myopia interrelate to influence the risk of retinal redetachment. Methods: This retrospective cohort study included patients with phakic RRD who had subsequent cataract extraction. The incidence and risk of redetachment were compared using Cox regression and χ2 analyses. Stratified analyses were performed based on time after cataract extraction, age, myopia status, and retinal repair type. Results: Of 1222 patients identified, no significant association was found between myopia and the incidence of redetachment, although the proportion of redetachments increased with the degree of myopia (nonmyopes, 8.5%, myopes, 9.5%, high myopes, 15.6%; P = .36). Myopia and high myopia were not associated with an increased risk of redetachment over time (hazard ratio, 1.01, P = .96; hazard ratio, 1.54, P = .35, respectively). Additionally, the incidence of redetachment was not significantly correlated with the time after cataract extraction (P = .33). A significant difference was observed between the incidence of redetachment and age (P = .003). Patients between 18 and 35 years experienced the highest incidence of redetachment within 1, 3, and 12 months after cataract extraction (5.26%, 7.02%, 7.02%, respectively). Such patients were overrepresented among those who underwent complex surgeries for initial phakic RRD repair (30-39 years, residual: 2.71; 40-49 years, residual: 3.32). Conclusions: Among patients with a phakic RRD, myopia did not significantly increase the risk of redetachment after cataract extraction. However, an upward trend was noted between the proportion of redetachments and the degree of myopia. Younger patients exhibited the highest incidence of redetachment and should be closely monitored after cataract extraction.
View details for DOI 10.1177/24741264261418517
View details for PubMedID 41756349
View details for PubMedCentralID PMC12932135