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Teprotumumab improves light sensitivity in patients with thyroid eye disease

  • Oculoplastics and Orbit
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Abstract

Background

Teprotumumab, a novel IGF-1R antibody, has been shown to significantly reduce the signs of acute and chronic Thyroid Eye Disease (TED). Light sensitivity is a reported symptom in patients with TED. There is a lack of a prospective study that has explored the effects on light sensitivity in a large cohort of patients with acute and chronic TED following treatment with teprotumumab.

Methods

Consecutive patients who were diagnosed with TED and reported light sensitivity at baseline were considered for study eligibility. All patients had measurements of Visual Light Sensitivity Questionnaire-8 (VLSQ-8), proptosis, clinical activity score (CAS), and MRD1 (distance between the upper eyelid margin and corneal reflex, mm) and MRD2 (distance between the lower eyelid margin and corneal reflex, mm) before and after treatment.

Results

Ninety patients (41 acute, 49 chronic) met the inclusion criteria. The mean (SD) age was 47.3 (14.3). Eighty-six (95.6%) patients completed all 8 infusions. There was a significant reduction in the total score and across all categories of the VLSQ-8 (p <  0.01 for all). Seventy-two (80%) patients had a clinically significant improvement (≥2 reduction) in at least one category. There was no significant difference in the total VLSQ-8 score between the acute and chronic group (p = 0.8).

Conclusion

Teprotumumab improves light sensitivity in patients with acute and chronic TED.

The results of this study highlight that the improvements in light sensitivity following treatment are not directly related to the mechanical changes in TED, suggesting another underlying mechanism is potentially involved.

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References

  1. Tsui S, Naik V, Hoa N et al (2008) Evidence for an association between thyroid-stimulating hormone and insulin-like growth factor 1 receptors: a tale of two antigens implicated in graves’ disease. J Immunol 181:4397–4405. https://doi.org/10.4049/jimmunol.181.6.4397

    Article  CAS  PubMed  Google Scholar 

  2. Ugradar S, Shi L, Wang Y et al (2021) Teprotumumab for non-inflammatory thyroid eye disease (TED): evidence for increased IGF-1R expression. Eye 35:2607–2612. https://doi.org/10.1038/s41433-020-01297-w

    Article  CAS  PubMed  Google Scholar 

  3. Smith TJ, Kahaly GJ, Ezra DG et al (2017) Teprotumumab for thyroid-associated Ophthalmopathy. N Engl J Med 376:1748–1761. https://doi.org/10.1056/NEJMoa1614949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Douglas RS, Kahaly GJ, Patel A et al (2020) Teprotumumab for the treatment of active thyroid eye disease. N Engl J Med 382:341–352. https://doi.org/10.1056/NEJMOA1910434

    Article  CAS  PubMed  Google Scholar 

  5. Ugradar S, Kang J, Kossler AL et al (2022) Teprotumumab for the treatment of chronic thyroid eye disease. Eye (Lond) 36:1553–1559. https://doi.org/10.1038/s41433-021-01593-z

    Article  CAS  PubMed  Google Scholar 

  6. Douglas RS, Couch S, Wester ST et al (2023) Efficacy and safety of teprotumumab in patients with thyroid eye disease of long duration and low disease activity. J Clin Endocrinol Metab 109:25–35. https://doi.org/10.1210/clinem/dgad637

  7. Cockerham KP, Padnick-Silver L, Stuertz N et al (2021) Quality of life in patients with chronic thyroid eye disease in the United States. Ophthalmol Ther 10:975–987. https://doi.org/10.1007/s40123-021-00385-8

    Article  PubMed  PubMed Central  Google Scholar 

  8. Ugradar S, Zimmerman E, Parunakian E et al (2023) Change in lacrimal gland volume and aqueous tear production following treatment with teprotumumab. Clin Experiment Ophthalmol 51:339–348. https://doi.org/10.1111/ceo.14208

    Article  PubMed  Google Scholar 

  9. Verriotto JD, Gonzalez A, Aguilar MC et al (2017) New methods for quantification of visual photosensitivity threshold and symptoms. Transl Vis Sci Technol 6:18. https://doi.org/10.1167/tvst.6.4.18

    Article  PubMed  PubMed Central  Google Scholar 

  10. Venkateswaran N, Hwang J, Rong AJ et al (2020) Periorbital botulinum toxin a improves photophobia and sensations of dryness in patients without migraine: case series of four patients. Am J Ophthalmol Case Rep 19:100809. https://doi.org/10.1016/j.ajoc.2020.100809

    Article  PubMed  PubMed Central  Google Scholar 

  11. Mourits MP, Koornneef L, Wiersinga WM et al (1989) Clinical criteria for the assessment of disease activity in graves’ ophthalmopathy: a novel approach. Br J Ophthalmol 73:639–644. https://doi.org/10.1136/bjo.73.8.639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Rüfer F, Schröder A, Erb C (2005) White-to-white corneal diameter. Cornea 24:259–261. https://doi.org/10.1097/01.ico.0000148312.01805.53

    Article  PubMed  Google Scholar 

  13. Villani E, Viola F, Sala R et al (2010) Corneal involvement in graves’ Orbitopathy: an in vivo confocal study. Investigative Opthalmology & Visual Science 51:4574. https://doi.org/10.1167/iovs.10-5380

    Article  Google Scholar 

  14. Wu L-Q, Cheng J-W, Cai J-P et al (2016) Observation of corneal Langerhans cells by in vivo confocal microscopy in thyroid-associated Ophthalmopathy. Curr Eye Res 41:927–932. https://doi.org/10.3109/02713683.2015.1133833

    Article  CAS  PubMed  Google Scholar 

  15. Oklar M, Yazicioglu T, Ozen MC et al (2023) Evaluation of corneal endothelium and correlation with disease severity in patients with graves’ ophthalmopathy: a specular microscopy-based study. Photodiagn Photodyn Ther 42:103592. https://doi.org/10.1016/j.pdpdt.2023.103592

    Article  CAS  Google Scholar 

  16. Wu Y-C, Zhu M, Robertson DM (2012) Novel nuclear localization and potential function of insulin-like growth Factor-1 receptor/insulin receptor hybrid in corneal epithelial cells. PLoS One 7:e42483. https://doi.org/10.1371/journal.pone.0042483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Nakamura M, Chikama T-I, Nishida T (2000) Characterization of insulin-like growth Factor-1 receptors in rabbit corneal epithelial cells. Exp Eye Res 70:199–204. https://doi.org/10.1006/exer.1999.0775

    Article  CAS  PubMed  Google Scholar 

  18. Rocha EM, Cunba DA, Carneiro EM et al (2002) Identification of insulin in the tear film and insulin receptor and IGF-1 receptor on the human ocular surface. Invest Ophthalmol Vis Sci 43

  19. Titone R, Zhu M, Robertson DM (2018) Insulin mediates de novo nuclear accumulation of the IGF-1/insulin hybrid receptor in corneal epithelial cells. Sci Rep 8:4378. https://doi.org/10.1038/s41598-018-21031-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Robertson DM, Zhu M, Wu Y-C (2012) Cellular distribution of the IGF-1R in corneal epithelial cells. Exp Eye Res 94:179–186. https://doi.org/10.1016/j.exer.2011.12.006

    Article  CAS  PubMed  Google Scholar 

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Funding

No funding was received for this research.

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Authors and Affiliations

  1. Private Practice, Beverly Hills, CA, USA

    Emanuil Parunakian, Shoaib Ugradar, Joseph Tolentino, Emil Malkhasyan, Pershanjit Raika, Joseph Ghaly, Chirag Bisht & Raymond S Douglas

Authors
  1. Emanuil Parunakian
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  2. Shoaib Ugradar
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  3. Joseph Tolentino
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  4. Emil Malkhasyan
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  5. Pershanjit Raika
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  6. Joseph Ghaly
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  7. Chirag Bisht
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  8. Raymond S Douglas
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Contributions

Raymond Douglas and Emanuil Parunakian were involved in the conception and design of the study. Emanuil Parunakian prepared the first manuscript; all authors were involved in drafting of the manuscript. All authors were involved in the data acquisition and analysis.

Corresponding author

Correspondence to Raymond S Douglas.

Ethics declarations

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the private practice of Dr. Raymond Douglas and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

The study was approved by the WCG-IRB (WCG, Puyallup, WA, USA) institutional review board (IRB No. 20210376).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Financial support

None.

Conflict of interest

Raymond Douglas is an employee of Sling Therapeutics. All other authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

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Parunakian, E., Ugradar, S., Tolentino, J. et al. Teprotumumab improves light sensitivity in patients with thyroid eye disease. Graefes Arch Clin Exp Ophthalmol (2024). https://doi.org/10.1007/s00417-024-06491-0

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  • DOI: https://doi.org/10.1007/s00417-024-06491-0

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