Romanian Journal of Ophthalmology, Volume 66, Issue 2, April-June 2022.

pp:153-157

CASE REPORT

DOI:10.22336/rjo.2022.30

A case report of a patient with severe thyroid eye disease

Mioara-Laura Macovei, Űnal Azis

Department of Ophthalmology, “Carol Davila” University of Medicine and Pharmacy, Bucharest 050474, Romania

Accepted: May 16th, 2022

Abstract
Correspondence to: Objective: Our aim was to present a rare case of a middle-aged male patient,
Unal Azis, diagnosed with Graves’ orbitopathy, which had an atypical rapid unilateral
Ophthalmology Department, “Dr. Carol onset. Initially, the left eye presented exophthalmos, eyelid retraction,
Davila” Central Military Emergency corneal ulceration, and pannus formation with an important vascular
University Hospital, Bucharest, component due to corneal exposure. The same symptoms developed in the
134 Calea Plevnei Street, District 1,
Bucharest, Romania,
right eye within a short period of time.
Mobile phone: +40744 626 997, Methods: A 52-year-old man presented in our department with bilateral
E-mail: resid_yunal@yahoo.com proptosis, decrease in visual acuity, and orbital pain, which developed
initially in the left eye seven months before the right eye. Slit lamp
examination revealed conjunctival hyperemia, purulent discharge, chemosis
and inflammation of the caruncle in both eyes. The fluorescein eye stain test
was positive due to corneal ulceration with the presence of cells and flare in
anterior chamber in the RE (right eye). The LE (left eye) presented a corneal
pannus. We documented the changes using a slit lamp biomicroscope, a
fundus camera, orbital ultrasonography, and contrast CT (computer
tomography) scans.
Discussions: The severe Graves’ ophthalmopathy represents a challenge
both in active or inactive phase. Medical and surgical therapies should be
taken into consideration in order to prevent the complications following
corneal perforation or optic neuropathy. Also, ophthalmic, and systemic
adverse reactions of systemic steroids used in the treatment of Graves’
disease are important in the prognosis of the visual outcome.
Conclusions: The management of Graves’ ophthalmopathy is
multidisciplinary and needs a very good therapy adherence in order to
achieve a satisfactory prognosis and quality of life.
Keywords: Graves’ disease, exophthalmos, corneal ulceration

Introduction rapid onset of orbitopathy are the predictors of

severe thyroid eye disease [2]. The target cells of the
Thyroid associated orbitopathy (TAO) represents immune process are represented by the pluripotential
an autoimmune, self-limiting disease that occurs in orbital fibrocytes, which are both found in orbital fat
patients with Graves’ disease (90%), Hashimoto tissue and striated muscle. TRAB (thyrotropin-
thyroiditis (3%), primary hypothyroidism (1%) or in receptor antibodies), also known as TSH-R (thyroid
the absence of thyroid abnormalities (6%) [1]. stimulating hormone receptor) are secreted by an
It is known as the most common orbital disease aberrant population of lymphocytes in Graves’
globally, which has a peak of incidence between disease. The circulating TRAB binds to CD40+
fourth and sixth decade. The risk factors for receptors expressed by the orbital fibrocytes and
developing TAO are represented by female gender, induces the upregulation of inflammatory cytokines
smokers, family history, life stressors and poorly such as IL-6, IL-8, and PGE E2, which increases the
controlled hypothyroidism following radioactive production of hyaluronan and glycosaminoglycan.
iodine, whereas male gender, increasing age and a The expansion of orbital fat is caused by a
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153
© 2022 The Authors.
Romanian Journal of Ophthalmology published by Romanian Society of Ophthalmology
Romanian Journal of Ophthalmology 2022; 66(2): 153-157

subpopulation of fibrocytes, which differentiates into evaluated. Ultrasound was performed and revealed
adipocytes. The clinical features depend on the orbital the enlargement of the extraocular muscles, without
tissue involved [2]. The most common symptoms and other particular signs. According to the European
signs of TAO are upper eyelid retraction (75%), lid lag Group on Graves’ Orbitopathy (EUGOGO) TED
with downgaze (50%), and dull orbital pain (35%). (thyroid eye disease) severity scale, the patient was
Most TAO patients develop a pattern that involves fat referred with “very serious disease”, due to corneal
expansion, has a slow progression, and occurs ulceration and had a clinical activity score (CAS) of 7
predominantly in young females. This pattern is at presentation (Fig. 3). The nervous system and
represented by eyelid retraction, proptosis, and systemic evaluation were normal.
ocular exposure [1]. The muscle centric pattern
affects older people, has an increased severity and it
is highly associated with smoking and family history
of TAO. The enlargement of the extraocular muscles
determines restricted ocular ductions, diplopia,
edema and congestion of eyelids and conjunctiva and
dysthyroid optic neuropathy [1].

Case presentation
A 52-year-old Caucasian male was referred to our
Ophthalmology Department for a one-month history
of bilateral orbital pain, proptosis and decrease in
visual acuity. The patient reported that the onset of
symptoms was unilateral, initially affecting the left
eye, for which he was diagnosed six months before
with preseptal cellulitis in another Ophthalmology
Service and was treated with systemic and topical
antibiotics, non-steroidal anti-inflammatories, Fig. 1 RE: Corneal inferior ulceration with KPs and
mydriatics and preservative free lubricants. The important hyperemia
symptoms did not improve after the initial treatment.
No family history of thyroid disease was known, nor
previous exposure to radioactive iodine. The patient
reported a recent decrease in visual acuity of the right
eye with blurring for approximately one month,
associated with anorexia, chronic headache, and
fatigability. He was also a heavy smoker (60 cigarettes
per day for more than 20 years). Physical examination
showed bilateral marked proptosis (24 mm in RE, 26
mm in LE), mainly affecting the left eye, eyelid
retraction, erythema and edema of the eyelids and
low-grade orbital pain on palpation. The best
corrected visual acuity was 0.6 on RE and the patient
perceived the hand movements with the LE. The
intraocular pressure was normal (12 mm Hg) in RE
and increased on palpation in the LE.
Ophthalmological examination revealed conjunctival
redness and purulent discharge, chemosis, Fig. 2 LE: Corneal pannus with vascularization
inflammation of caruncles, evident restriction of the
movement in both eyes. An inferior marginal corneal
ulceration, cells, and flare in the anterior chamber and The patient was admitted to hospital for further
keratic precipitates on the posterior surface of the investigations, endocrinologic assessment and
cornea were documented in the RE (Fig. 1). A corneal management. Initial blood investigations, including
pannus affected the two-thirds of the cornea of the LE blood count, liver biochemistry, glycemia, serum
with the presence of dilated, tortuous vessels (Fig. 2). electrolytes, fasting lipid profile, serum creatinine,
Fundus evaluation of the right eye was normal, blood urea nitrogen, erythrocyte sedimentation rate,
without suggestive signs for dysthyroid optic C reactive protein were normal. The thyroid function
neuropathy, whereas the left eye could not be and antibody tests were also performed, revealing

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Romanian Journal of Ophthalmology
 Romanian Journal of Ophthalmology 2022; 66(2): 153-157

hyperthyroidism based on high levels of FT3 and FT4, reduce the modifiable risk factors such as smoking.
with low TSH. The presence of high levels of TSH-R The patient received effective support in order to
autoantibodies suggested an active phase of Graves’ cease smoking. A clinical study revealed that cigarette
disease. Orbital imaging confirmed the diagnosis smoking may corelate with increase in retrobulbar
based on contrast CT scans, which showed venous congestion in thyroid associated
enhancement of the extraocular muscle sheaths and ophthalmopathy [4].
stranding of surrounding orbital fat, typical findings A regular follow-up of the thyroid function at four
for the active inflammatory phase. Cerebral MRI weeks depending on the severity of the disease [5]
(magnetic resonance imaging) confirmed the absence and an ophthalmologic assessment was
of dysthyroid optic neuropathy or the presence of recommended by the endocrinologist. At the first
other lesions. The ultrasound exam of thyroid gland month follow-up, the patient showed a suboptimal
revealed: mixed echogenicity, diffusely enlarged response to high dose intravenous
thyroid gland, inhomogeneous structure and ventrally methylprednisolone. We observed an increase of the
hypoechoic micronodular structure. Following the CAS score suggested by the exophthalmos, which was
endocrinologic assessment and ophthalmic similar to the previous examination, a decrease of
examination, the diagnosis of severe Graves’ best corrected visual acuity in RE and perception of
ophthalmopathy was established. hand movements in the LE, while the corneal
ulceration showed a slight amelioration (Fig. 4). The
thyroid function test showed euthyroidism. The liver
and renal function were assessed and both were
normal. The endocrinologist decided to continue the
corticosteroid therapy in order to cease the
inflammation. The radiotherapy or decompression
surgery were not suitable in this case.

Fig. 3 Right eye (RE) at presentation

The patient was hospitalized for two weeks. A

protocol with intravenous methylprednisolone 500
mg weekly for 6 weeks, reduced to 250 mg weekly for
6 weeks was initiated. Topical broad-spectrum
antibiotics were instilled in both eyes. Preservative- Fig. 4 RE: Slight improvement of the corneal ulceration
free lubricants were used in order to relief the
symptoms of corneal exposure and a mydriatic was
administered 3 times per day in the right eye in order At the sixth month follow-up, the ophthalmologic
to avoid the formation of posterior synechiae. The IOP examination revealed an improvement of
of the LE was lowered by using a topical combination exophthalmos in both eyes and a corneal pannus in
of timolol and dorzolamide. Doxycycline was also RE similar to LE (Fig. 5). The visual acuity in RE
administered due to its efficiency in the treatment of showed an important decrease caused by a cataract,
inflammatory ocular conditions by inhibiting the which developed secondary to systemic
synthesis and the release of corneal MMPs [3]. corticosteroid therapy. The thyroid test function
Patching of both eyes during night was also revealed a drug-induced hypothyroidism and the
performed. Thyrozol and propranolol were treatment was switched to thyroid hormones
prescribed to optimize the thyroid function. The substitutes. The patient delayed the surgical
patient was also instructed to cease smoking. A target treatment of the cataract. The following
in the management of Graves’ ophthalmopathy is to

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Romanian Journal of Ophthalmology 2022; 66(2): 153-157

ophthalmologic and endocrinologic exams did not ocular surface lubricating therapies are an important
reveal any modification of his status. tool in the treatment of the exposure keratopathy [8].
The corneal involvement could be related to
inflammatory processes including the systemic
disease itself and the dry eye syndrome (DES) [11].
DES is common even in the early phases of Graves’
ophthalmopathy without exophthalmos. In Graves’
orbitopathy, DES is mainly evaporative due to corneal
exposure and it can also be associated with CAS and
reduced corneal sensitivity [12]. The alterations of
the lacrimal film of these patients are caused by the
impairment of the extraocular muscles and the
immune-mediated dysfunction of the lacrimal glands
[13].
The severe exposure keratopathy represents an
urgence, thus decompression surgery could be
indicated. In the active phase, local treatment such as
tarsorrhaphies, corneal patches, or gluing can be used
in order to avoid corneal perforation or to treat the
corneal breakdown, while in the inactive phase,
Fig. 5 RE: Pannus formation and secondary cataract
with synechiae decompression, ophthalmic plastic, and strabismus
surgery can be an important tool for the repair of
residual damage (exophthalmos, lid retractions,
Discussion eyelid, and periorbital puffiness, strabismus) [7].
The thyroid associated ophthalmopathy has a
biphasic evolution, which was described by Rundle:
Conclusions
an active, dynamic phase, which has a mean duration In conclusion, severe forms of Graves’
of 6-18 months [1] and an inactive, static phase [6]. In ophthalmopathy are sight-threatening and need a
the dynamic phase, the immunomodulatory multidisciplinary approach of the management of the
treatment and external beam radiotherapy are disease and its complications. Also, the therapy
recommended in order to cease inflammation, while adherence and modifiable risk factors, such as
in the static phase, reconstructive surgery can be smoking, play a major role for the outcome of the
attempted [1]. Graves’ ophthalmopathy.
The management of moderate-to-severe Graves’
ophthalmopathy consists of the control of the risk Conflict of Interest Statement
factors, local treatments, and immunosuppression [7]. The authors state no conflict of interest.
A recent study concerning the trends in the
treatment of active thyroid associated Informed Consent and Human and Animal Rights
ophthalmopathy concludes that aggressive therapies statement
such as oral or IV glucocorticoids, Rituximab and/ or Informed consent has been obtained from the
Tocilizumab and orbital radiotherapy are used in the patient included in the study.
severe forms [8]. IV glucocorticoids in association
with mycophenolate mofetil represent the first line Authorization for the use of human subjects
therapy, while the oral prednisone or prednisolone Ethical approval: The research related to human
with Azathioprine or Cyclosporine, Rituximab, use complies with all the relevant national
Tocilizumab, and orbital radiation with oral or IV regulations, institutional policies, it is in accordance
glucocorticoids are the second line therapy [7]. with the tenets of the Helsinki Declaration and has
A novel IGF-1R (insulin growth-factor-1 receptor) been approved by the review board of Department of
antibody, Teprotumumab, plays an important role in Ophthalmology, “Carol Davila” Central Military
the treatment of active Graves’ ophthalmopathy [9]. University Hospital, Bucharest, Romania.
Also, in chronic phase, it showed benefits on
proptosis, inflammation, diplopia, strabismus, and Acknowledgements
orbital soft tissue volume [10]. None.
Moreover, topical steroids are prescribed in order
to manage the symptoms of ocular inflammation Sources of Funding
consisting of dryness and hyperemia. Likewise, the None.

156 © 2022 The Authors.

Romanian Journal of Ophthalmology
 Romanian Journal of Ophthalmology 2022; 66(2): 153-157

Disclosures
None.

Contribution
Both authors contributed equally to this article.

References

1. Yanoff M, Duker JS. Ophthalmology, the Fourth Edition, 2011.

2. A. A. of Ophthalmology. Oculofacial Plastic and Orbital
Surgery. 53(9).
3. Smith VA, Cook SD. Doxycycline—a role in ocular surface
repair. Br. J. Ophthalmol. May 2004; 88(5):619 LP–625. doi:
10.1136/bjo.2003.025551.
4. Sadeghi-Tari A et al. Effect of smoking on retrobulbar blood
flow in thyroid eye disease. Eye. 2016; 30(12):1573–1578.
doi: 10.1038/eye.2016.184.
5. Perros P, Neoh C, Dickinson J. Thyroid eye disease. BMJ. Mar.
2009; 338:b560. doi: 10.1136/bmj.b560.
6. Bartley G. Rundle and His Curve. Arch. Ophthalmol. Mar.
2011; 129:356–358. doi: 10.1001/archophthalmol.2011.29.
7. Bartalena L et al. The 2021 European Group on Graves’
orbitopathy (EUGOGO) clinical practice guidelines for the
medical management of Graves’ orbitopathy. Eur. J.
Endocrinol. 2021; 185(4):G43–G67. doi: 10.1530/EJE-21-
0479.
8. Wang Y et al. Trends in Treatment of Active, Moderate-to-
Severe Thyroid Eye Disease in the United States. J. Endocr.
Soc. Dec. 2020; 4(12), doi: 10.1210/jendso/bvaa140.
9. Douglas RS et al. Teprotumumab for the Treatment of Active
Thyroid Eye Disease. N. Engl. J. Med. Jan. 2020; 382(4):341–
352. doi: 10.1056/NEJMoa1910434.
10. Ugradar S et al. Teprotumumab for the treatment of chronic
thyroid eye disease. Eye. 2021. doi: 10.1038/s41433-021-
01593-z.
11. Villani E et al. Corneal Involvement in Graves’ Orbitopathy:
An In Vivo Confocal Study Invest. Ophthalmol. Vis. Sci. Sep.
2010; 51(9):4574–4578. doi: 10.1167/iovs.10-5380.
12. Achtsidis V et al. Dry Eye in Graves’ Ophthalmopathy:
Correlation with Corneal Hypoesthesia. Eur. J. Ophthalmol.
Apr. 2013; 23(4):473–479. doi: 10.5301/ejo.5000259.
13. Selter J, Gire A, Sikder S. The relationship between Graves’
ophthalmopathy and dry eye syndrome. Clin. Ophthalmol.
Jan. 2015; 9:57–62, doi: 10.2147/OPTH.S76583.

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