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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Teprotumumab for thyroid eye disease in patients with hypothyroid/euthyroid state: a multicenter case series.
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie
Ugradar, S., Parunakian, E., Malkhasyan, E., Raika, P., Tolentino, J., Kossler, A. L., Cockerham, K., Amarikwa, L., Weinberg, D. A., Douglas, R. S.
2024
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Abstract
Teprotumumab, a novel IGF-1R antibody was recently shown to significantly reduce the signs of acute and chronic thyroid eye disease (TED) related to hyperthyroidism. Given the lower incidence of TED associated with hypothyroidism / euthyroidism, there is a paucity of data regarding the efficacy of teprotumumab in this group.In this multicenter study, consecutive patients who had been diagnosed with TED, presenting with either hypothyroidism or euthyroidism as their baseline thyroid dysfunction and treated with teprotumumab were included. All patients had measurements of proptosis, clinical activity scores (CAS), diplopia scores and four-point strabismus scores before and after therapy.Twenty-six patients met the inclusion criteria. Mean age was 48 ± 14 years old and mean duration of TED prior to treatment was 31 ± 43 months. All patients received 8 infusions. Mean (SD) reduction in proptosis for study orbits was 2.7 mm (1.8) (p < 0.05) and 1.8 mm (2.0) for the fellow orbit (p < 0.05). In the study orbit, mean (SD) CAS was 2.3 (1.3) before therapy and 1.0 (1.0) following therapy (p < 0.05). At baseline, mean (SD) diplopia score was 1.2 (1.1) and 0.9 (1.1) following therapy (p < 0.05).Teprotumumab reduces proptosis and inflammation in patients presenting with TED associated with hypothyroidism and euthyroidism. The results of this study highlight the potential for teprotumumab therapy in this subgroup and also provide a unique insight into the potential role of the IGF-1R in these patients.
View details for DOI 10.1007/s00417-024-06599-3
View details for PubMedID 39136754
View details for PubMedCentralID 3213650
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Impact of Obstructive Sleep Apnea on Diabetic Retinopathy Progression and Systemic Complications.
American journal of ophthalmology
Rahimy, E., Koo, E. B., Wai, K. M., Ludwig, C. A., Kossler, A. L., Mruthyunjaya, P.
2024
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Abstract
Evaluate the risk of diabetic retinopathy progression and systemic vascular events, including death, in patients with non-proliferative diabetic retinopathy (NPDR) with obstructive sleep apnea (OSA).Retrospective cohort study.Electronic chart query using TriNetX (Cambridge, MA, USA), an electronic health records network comprising data from over 124 million patients. Patients with NPDR with and without OSA were identified. Patients were excluded if they had history of proliferative disease (PDR), diabetic macular edema (DME), or prior ocular intervention (intravitreal injection, laser, or pars plana vitrectomy). Propensity score matching was performed to control for baseline demographics and comorbidities. Rate of progressing to vision threatening complications (VTCs), need for ocular intervention, and systemic events was measured at 1, 3, and 5 years.11,931 patients in each group were analyzed after propensity score matching. There was elevated risk of PDR in the OSA cohort at 1 (RR: 1.34, P<0.001), 3 (RR: 1.31, P<0.001), and 5 years (RR: 1.28, P<0.001). There was elevated risk of DME in the OSA group at all time points: 1 (RR: 1.31, P<0.001), 3 (RR: 1.19, P<0.001), and 5 years (RR: 1.18, P<0.001). With respect to ocular interventions, there was an increased risk of intravitreal injection in OSA patients at 1 (RR: 1.59, P<0.001), 3 (RR: 1.58, P<0.001), and 5 years (RR: 1.54, P<0.001), and similar trends were noted with laser photocoagulation, but not vitrectomy. Regarding systemic events, NPDR patients with OSA had a greater risk of stroke (1 year RR: 1.80, P<0.001; 3 year RR: 1.56, P<0.001; 5 year RR: 1.49, P<0.001), myocardial infarction (1 year RR: 1.51, P<0.001; 3 year RR: 1.46, P<0.001; 5 year RR: 1.43, P<0.001), and death (1 year RR: 1.31, P<0.001; 3 year RR: 1.19, P<0.001; 5 year RR: 1.15, P<0.001).There is an increased rate of DR progression to VTCs, need for ocular intervention, and systemic complications, including death, for patients with OSA. We emphasize the need for improved screening measures of patients with NPDR and potential OSA.
View details for DOI 10.1016/j.ajo.2024.07.021
View details for PubMedID 39089360
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Re: Shah et al.: Teprotumumab-related adverse events in thyroid eye disease: a multicenter study (<i>Ophthalmology</i>. 2024;131:458-467) REPLY
OPHTHALMOLOGY
Shah, S. A., Amarikwa, L., Sears, C. M., Clauss, K. D., Rajjoub, R. D., Kang, J. Y., Tamhankar, M. A., Briceno, C. A., Harrison, A. R., Cockerham, K. P., Wester, S. T., Douglas, R. S., Dosiou, C., Kossler, A. L.
2024; 131 (6): e27-e28
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View details for Web of Science ID 001247989300001
View details for PubMedID 38724205
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An Analysis of Solicitations from Predatory Journals in Ophthalmology.
American journal of ophthalmology
Justin, G. A., Huang, C., Nguyen, M. K., Lee, J., Seddon, I., Wesley, T. A., Bakri, S. J., Campbell, J. P., Cavuoto, K., Collins, M., Gedde, S. J., Kossler, A. L., Milman, T., Shukla, A., Sridhar, J., Syed, Z. A., Williams, B. K., Woreta, F. A., Patel, S. N., Yonekawa, Y.
2024
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Abstract
To evaluate trends associated with email communication from potentially predatory publishers to faculty in ophthalmology.Cross sectional study METHODS: Ophthalmologists (n=14) from various subspecialties and institutions were recruited to participate. Participants identified unsolicited emails they had received originating from publishers in May 2021. Information collected included details on email contents and publisher organizations. Trends in communications from predatory publishers were evaluated.Over a 30-day study period, a total of 1813 emails were received from 383 unique publishers and 696 unique journals with a mean (SD) of 4.73 (2.46) emails received per day per participant. Of the 1813 emails identified, 242 (13%) emails were invitations to conferences, whereas 1440 (80%) were solicitations for article submissions to open-access pay-to-publish journals. A total of 522 (29.0%) emails were related to ophthalmology, and reference to a prior publication of the participant occurred in 262 emails (14%). Of the 696 unique journals identified, 174 (25%) journals were indexed on PubMed and 426 (61%) were listed on Beall's list. When comparing journals listed on PubMed versus those that were not, PubMed indexed journals had a higher impact factor (2.1 vs 1.5, p=0.002), were less likely to use "greetings" (76% vs 91%, p<0.001), had fewer spelling/grammar errors (40% vs 51%, p=0.01), and were less likely to offer rapid publication (16% vs 25%, p=0.02).Unsolicited requests to publish occur frequently and may diminish the quality of the scientific literature. We encourage individuals in ophthalmology to be aware of these trends in predatory publishing.
View details for DOI 10.1016/j.ajo.2024.02.030
View details for PubMedID 38490339
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Association of ocular manifestations of Marfan syndrome with cardiovascular complications.
American journal of ophthalmology
Tran, E. M., Wai, K. M., Kossler, A. L., Mruthyunjaya, P., Rahimy, E., Koo, E. B.
2024
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To evaluate associations between ocular manifestations of Marfan syndrome and cardiovascular complications.retrospective cohort study METHODS: Setting: TriNetX Analytics platform, a federated health research network of aggregated deidentified electronic health record data of over 119 million patients.Patients diagnosed with Marfan syndrome.Univariate logistic regression models were used to evaluate the association of ocular manifestations of Marfan syndrome (such as retinal tears/detachment, lens dislocation, and myopia), with cardiovascular comorbidities. Additional sensitivity analyses were performed using propensity matching.Odds ratio and 95% confidence intervals for incidence of cardiovascular comorbidities (including aortic dissection, valvular disease, and arrhythmias) following diagnosis of Marfan syndrome.19,105 patients were identified that were diagnosed with Marfan disease without ocular manifestations, and an additional 3,887 Marfan patients with ocular comorbidities. Patients who were diagnosed with ocular disease included 883 with ectopic lens, 417 with retinal tear or detachment, 683 with aphakia, 534 with pseudophakia, and 2,465 with myopia. Patients with any ocular manifestations of Marfan were significantly more likely to be diagnosed with all cardiovascular comorbidities modeled including aortic aneurysm and dissection (OR=2.035; p=<0.0001), mitral valve prolapse (OR=2.725; p= p=<0.0001), tricuspid valve disorders (OR=2.142; p=<0.0001), cardiac arrhythmias (OR=1.836; p=<0.0001), and all cardiovascular outcomes combined (OR=2.194; p=<0.0001).In a large and diverse cohort of patients with Marfan syndrome, ocular manifestations of the disorder appear strongly associated with cardiovascular comorbidities.
View details for DOI 10.1016/j.ajo.2024.02.023
View details for PubMedID 38403098
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Reply.
Ophthalmology
Shah, S. A., Amarikwa, L., Sears, C. M., Clauss, K. D., Rajjoub, R. D., Kang, J. Y., Tamhankar, M. A., Briceño, C. A., Harrison, A. R., Cockerham, K. P., Wester, S. T., Douglas, R. S., Dosiou, C., Kossler, A. L.
2024
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View details for DOI 10.1016/j.ophtha.2024.01.003
View details for PubMedID 38349298
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Anatomic and Surgical Considerations in the Management of a Sellar and Suprasellar Arachnoid Cyst: 2-Dimensional Operative Video.
Operative neurosurgery (Hagerstown, Md.)
Rychen, J., Constanzo, F., Chan, D., Kossler, A. L., Fernandez-Miranda, J. C.
2024
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View details for DOI 10.1227/ons.0000000000001061
View details for PubMedID 38198191
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Teprotumumab for the Treatment of Recalcitrant Thyroid Eye Disease.
Ophthalmic plastic and reconstructive surgery
Men, C. J., Amarikwa, L., Pham, B., Sears, C., Clauss, K., Lee, B. W., Lee, W. W., Pasol, J., Ugradar, S., Shinder, R., Cockerham, K., Wester, S., Douglas, R., Kossler, A. L.
2023
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Abstract
Teprotumumab, an insulin-like growth factor 1 receptor monoclonal antibody, is FDA-approved to treat thyroid eye disease (TED). The initial clinical trials excluded patients with previous orbital irradiation, surgery, glucocorticoid use (cumulative dose >1 gm), or prior biologic treatment. Information on the use of teprotumumab for patients who failed prior therapy is limited. Our purpose is to characterize the efficacy of teprotumumab for the treatment of recalcitrant TED.This is a multicenter retrospective study of all patients treated with teprotumumab for moderate-to-severe TED after failing conventional therapy with corticosteroids, orbital radiation, surgical decompression, biologics, or other steroid-sparing medications. Treatment failure was defined as an incomplete response to or reactivation after previous treatment. Only patients who received at least 4 infusions of teprotumumab were included in the analysis. Primary outcome measures comprised proptosis response (≥2 mm reduction in the study eye without a similar increase in the other eye), clinical activity score (CAS) response (≥2-point reduction in CAS), and diplopia response (≥1 point improvement in Gorman diplopia score in patients with baseline diplopia) following treatment. Adverse events and risk factors for recalcitrant disease were also evaluated.Sixty-six patients were included in this study, 46 females and 20 males. Average age was 59.3 years (range 29-93). The mean duration of disease from TED diagnosis to first infusion was 57.8 months. The proptosis, CAS, and diplopia responses in this recalcitrant patient population were 85.9%, 93.8%, and 69.1%, respectively. Patients experienced a mean reduction in proptosis of 3.1 ± 2.4 mm and a mean improvement in CAS of 3.8 ± 1.6. Patients who underwent prior decompression surgery experienced a statistically significant decrease in diplopia response (46.7% vs. 77.5%, p = 0.014) and proptosis response (75.0% vs. 90.9%, p = 0.045) when compared with nondecompression patients. Additionally, there were no significant differences in proptosis, CAS, and diplopia responses between patients with acute (defined as disease duration <1 year) versus chronic (disease duration ≥1 year) TED. While most adverse events were mild to moderate, 4 patients reported serious adverse events related to persistent hearing loss.Patients with recalcitrant TED demonstrated a significant improvement after teprotumumab in each of the primary study outcomes. The degree of proptosis reduction, diplopia response, and CAS improvement in the recalcitrant group were similar to those of treatment-naïve patients from the pivotal clinical trials. Patients with a prior history of orbital decompression, however, demonstrated poor improvement in diplopia and less reduction in proptosis than surgery naïve patients. These results indicate that teprotumumab is a treatment option for the treatment of patients with TED recalcitrant to prior medical therapies.
View details for DOI 10.1097/IOP.0000000000002564
View details for PubMedID 37972960
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Teprotumumab-Related Adverse Events in Thyroid Eye Disease: A Multi-Center Study.
Ophthalmology
Shah, S. A., Amarikwa, L., Sears, C. M., Clauss, K. D., Rajjoub, R. D., Kang, J. Y., Tamhankar, M. A., Briceño, C. A., Harrison, A. R., Dosiou, C. C., Cockerham, K. P., Wester, S. T., Douglas, R. S., Kossler, A. L.
2023
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Abstract
To assess the duration, incidence, reversibility, and severity of adverse events (AEs) in patients with thyroid eye disease (TED) treated with teprotumumab.Multi-center retrospective observational cohort study.Patients with TED of all stages and activity levels treated with at least 4 infusions of teprotumumab.Patients were treated with teprotumumab between February 2020 and October 2022 at 6 tertiary centers. AE metrics were solicited and recorded at each visit. AEs were grouped according to the United States FDA Adverse Event Reporting System.Primary outcomes measure: AE incidence and onset.AE severity, reversibility, duration, proptosis response, clinical activity score (CAS) reduction, and Gorman diplopia score (GDS) improvement.The study evaluated 131 patients. Proptosis improved by 2mm or more in 77% (101/131) of patients with 3.0±2.1mm average proptosis improvement and 3.2 points average CAS reduction. GDS improved by at least one point for 50% (36/72) of patients with baseline diplopia. AEs occurred in 81.7% (107/131) of patients. Patients had a median of 4 AEs. Most patients' AEs were mild (74.0%, 97/131), 28.2% (37/131) moderate, and 8.4% (11/131) severe. Mean interval AE onset was 7.9 weeks after the first infusion. Resolved AEs had a mean duration of 17.6 weeks. Forty-six percent (60/131) of patients had at least 1 persistent AE at last follow-up. Patients had a mean follow-up of 70.2±38.5 weeks after the first infusion. The most common type of AEs was musculoskeletal (58.0%, 76/131), followed by gastrointestinal (38.2%, 50/131), skin (38.2%, 50/131), ear and labyrinth (30.5%, 40/131), nervous system (20.6%, 27/131), metabolic (15.3%, 20/131), and reproductive system (12.2%, 16/131). Sixteen patients (12.2%) discontinued therapy due to AEs, including hearing loss (n=4), inflammatory bowel disease flare (n=2), hyperglycemia (n=1), muscle spasms (n=1), and multiple AEs (n=8).AEs are commonly reported while receiving teprotumumab treatment. Most are mild and reversible; however, serious AEs can occur and may warrant treatment cessation. Treating physicians should inform patients about the AE risk, properly screen patients prior to treatment, monitor patients closely throughout therapy, and understand how to manage AEs should they develop.
View details for DOI 10.1016/j.ophtha.2023.10.018
View details for PubMedID 37852417
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Accuracy of Digital Image Analysis for Diagnosing IgG4 Related Ophthalmic Disease
Charoenkijkajorn, C., Gill, H., Glory, B., Shi, W., Homer, N., Men, C., Kossler, A., Wu, A., Lin, J.
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023
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View details for Web of Science ID 001053795606146