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\title{Methotrexate Monotherapy for Unilateral Active Thyroid-Related Eye
Disease}



\author[1]{Ayman Elnahry}%
\author[2]{Joseph Talbet}%
\author[1]{Gehad Elnahry}%
\affil[1]{Cairo University Kasr Alainy  Faculty of Medicine}%
\affil[2]{Howard University College of Medicine}%


\vspace{-1em}



  
  \date{April 25, 2026}


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\selectlanguage{english}
\begin{abstract}
A type 1 diabetic patient with unilateral active thyroid-related eye
disease was intolerant to systemic steroid therapy due to uncontrollable
blood sugar levels. She was treated with low-dose methotrexate
monotherapy which resulted in a marked improvement of her condition with
no adverse events.%
\end{abstract}%



\sloppy


\textbf{Methotrexate Monotherapy for Unilateral Active Thyroid-Related
Eye Disease}

Ayman G. Elnahry\textsuperscript{1} M.D., Ph.D., Joseph H.
Talbet\textsuperscript{2} B.A., Gehad A. Elnahry\textsuperscript{1}M.D.,
Ph.D.

\textsuperscript{1}Department of Ophthalmology, Faculty of Medicine,
Cairo University, Cairo, Egypt.

\textsuperscript{2} College of Medicine, Howard University, Washington,
DC, USA.

\textbf{Corresponding author, and correspondence to:} Ayman G. Elnahry
M.D., Ph.D., Department of Ophthalmology, Cairo University, Faculty of
Medicine, Kasr Alainy street, Cairo, Egypt 11956. Phone: +20-1224927604.
Fax: +20223682030. E-mail: ayman\_elnahri@hotmail.com

\textbf{Running title:} Methotrexate for Active Thyroid Eye Disease

\textbf{Ethical approval:} This report was approved by Cairo University
research ethics committee and followed the tenets of the Declaration of
Helsinki

\textbf{Financial support:} None

\textbf{Conflicts of Interest and Source of Funding:} None

\textbf{Keywords:} Euthyroidism; Methotrexate; Monotherapy;
Thyroid-related eye disease.

\textbf{Key Clinical Message:} Active thyroid-related eye disease may be
safely and effectively managed using low-dose methotrexate monotherapy
especially in patients intolerant to steroid therapy.

\emph{Abstract}

A type 1 diabetic patient with unilateral active thyroid-related eye
disease was intolerant to systemic steroid therapy due to uncontrollable
blood sugar levels. She was treated with low-dose methotrexate
monotherapy which resulted in a marked improvement of her condition with
no adverse events.

\emph{Case Description}

A 43-year-old female presented with right eye redness and pain of
gradual onset and insidious course. She had diabetes mellitus for 25
years controlled by insulin. Her best corrected vision was 20/20
bilaterally with 12/12 color vision and no afferent pupillary defect.
She had mild right ocular motility limitation. External exam showed
eyelid edema and 23 mm protrusion of the right eye compared to 20 mm in
the left by exophthalmometry. There was also mild right upper eyelid
retraction with increased inferior scleral show (Figure 1A). Slit-lamp
examination showed dilated right conjunctival vessels with normal
anterior and posterior segments. Orbital MRI revealed right extraocular
muscle enlargement with tendon sparing (Figure 1B). Laboratory
investigations showed normal free-T3, free-T4, and thyroid-stimulating
hormone (TSH) levels but positive TSH-receptor antibodies and she was
diagnosed with unilateral active thyroid-related eye disease (TED) and
prescribed 60 mg/day of oral prednisone. After 2 weeks, however, she was
intolerant to steroid due to uncontrollable blood sugar levels and was
rapidly tapered off treatment and prescribed 10 mg of methotrexate
weekly as monotherapy. Six months later she experienced marked
improvement (Figure 1C) and was gradually tapered off methotrexate
without relapse.

TED usually occurs with hyperthyroidism but can also rarely occur with
hypothyroidism or euthyroidism.\textsuperscript{1} It can be unilateral
or bilateral, and in cases of euthyroidism, requires the detection of
anti-thyroid antibodies for diagnosis. The mainstay of treatment of
moderate to severe active TED is glucocorticoids, however, methotrexate
monotherapy can be safe and effective in cases of glucocorticoid
intolerance.\textsuperscript{2}

\emph{Ethics statement}

Written informed consent for publication of photographs was obtained
from the patient and is available upon request. This case report did not
receive any funding. Authors have access to all source data for this
case report.

\emph{Acknowledgements}

None.

\emph{Conflict of interest}

None.

\emph{Author contributions}

AGE has made substantial contributions in the acquisition and
interpretation of data, and in drafting of the manuscript. JHT has made
substantial contributions in the analysis and interpretation of the
data, and in revising the manuscript. GAE treated the patient and has
made substantial contributions in the acquisition and interpretation of
data, and in revising the manuscript. All authors read and approved the
final version of the manuscript and agree to be accountable for all
aspects of the work.

\emph{References}

Khong, J. J., McNab, A. A., Ebeling, P. R., Craig, J. E., and Selva, D.
2016. Pathogenesis of thyroid eye disease: review and update on
molecular mechanisms. The British journal of ophthalmology 100(1):
142--150.

Rubinov, A., Zommer, H., Aghazadeh, H., and Weis, E. 2018. Role of
methotrexate in thyroid-related orbitopathy. Canadian journal of
ophthalmology. Journal canadien d'ophtalmologie 53(1): 34--38.

\emph{Figure legend}

\emph{Figure 1:}

At presentation, there was redness, proptosis, upper eyelid edema and
retraction, and increased inferior scleral show of the right eye
compared to the left (\textbf{A} ). Magnetic resonance imaging of the
orbit revealed an enlargement of the extraocular muscles of the right
eye compared to the left (\textbf{B} ). Six months following
methotrexate monotherapy, there was marked improvement of the clinical
condition apart from mild residual conjunctival chemosis (\textbf{C} ).\selectlanguage{english}
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