The eye: "mirror" of physical health?
We look at the symptoms and diagnostic criteria of endocrine orbitopathy, a progressive and very common inflammatory disease of the eye orbit.
Is there an optimal treatment for endocrine orbitopathy?
Endocrine orbitopathy is an autoimmune inflammatory disease of the orbit that can be associated with significant ocular morbidity. The typical presentation consists of exophthalmos, eyelid retraction and associated widening of the palpebral fissure. Exophthalmos is an important part of the Merseburg triad. This symptom complex also includes tachycardia and goiter. Exophthalmos is measured with an exophthalmometer. In addition, intraocular pressure measurement, perimetry, assessment of the eye muscles, determination of the palpebral fissure width and, if possible, optic disc OCT diagnostics should be performed. Sicca syndrome symptoms associated with exophthalmos can be determined by Schirmer's test or BUT test.1
The consequences of upper eyelid retraction and exophthalmos
Unilateral or bilateral upper eyelid retraction is one of the most common signs of endocrine orbitopathy. It occurs in over 90% of people affected by Graves' disease. Exophthalmos itself is second in frequency of occurrence. It occurs in 60% of patients. Lagophthalmos (incomplete closure of the eyelids) is present in 50% of cases. Chronic exposure of the eyes leads to sicca symptoms. If the condition persists for a long time, it can result in severe keratopathy without adequate treatment. This brings further risks with it. Scarring and associated corneal opacity, perforation and, in the worst case, endophthalmitis may occur.1
Ocular muscle involvement in endocrine orbitopathy
40 % of patients unfortunately suffer from dysfunction of the extraocular muscles. This can lead to diplopia. In most cases, the medial rectus muscle and the inferior rectus muscle are affected, which may be manifested by the appearance of hypotropia (downward deviation) or esotropia (inward deviation).1
Staged therapy for endocrine orbitopathy
A few years ago, Prof. Dr. Anja Eckstein already advocated the following step-by-step scheme, in which the therapy of endocrine orbitopathy is oriented towards the severity of the disease:
- Mild form of endocrine orbitopathy 🡪 Supplementation with selenium and, if necessary, intravenous steroid therapy.
- Moderate form of endocrine orbitopathy 🡪 Intravenous steroid therapy in combination with radiation. This combination therapy can be supplemented with biologics or immunosuppressants.
- Severe form of endocrine orbitopathy 🡪 Immediate surgical relief of the orbit.2
European guidelines on the treatment of endocrine orbitopathy
The European guideline recommends the choice of treatment based on the assessment of clinical activity as well as the severity of the endocrine orbitopathy. In mild endocrine orbitopathy with inflammatory activity, control of risk factors, local treatment, and selenium supplementation are advised. If risk factors are present, combination of radioiodine therapy with low-dose oral prednisone prophylaxis is recommended.
Intravenous steroid therapy should be preferred to oral administration in active moderate to severe endocrine orbitopathy as well as in vision-threatening endocrine orbitopathy. The combination of i.v. methylprednisolone and mycophenolate sodium is also recommended as initial treatment.
The optimal treatment regimen is a cumulative dose of 4.5g i.v. methylprednisolone every 12 weeks. In second-line treatment of moderate to severe endocrine orbitopathy with inflammatory activity, the following options are available:
- The second administration of i.v. methylprednisolone (7.5 g).
- Administration of oral prednisone/prednisolone in combination with cyclosporine or azathioprine.
- Orbital radiotherapy in combination with oral or i.v. glucocorticoids.
- Teprotumumab.
- Rituximab.
- Tocilizumab.3
Where do we stand on targeted therapies for endocrine orbitopathy?
On 21 January 2020, the FDA approved the monoclonal antibody as the first drug for the treatment of endocrine orbitopathy in Graves' disease. Teprotumumab (Tepezza®) is directed against the IGF-1 receptor and has "orphan drug" status. In the pivotal study, the use of teprotumumab avoided the need for decompression surgery in some patients.
In low and also in high inflammatory activity, teprotumumab was able to significantly reduce exophthalmos.4,5 However, concerns about teprotumumab have been raised by endocrinology professionals. Prof. Helmut Schatz wrote in 2021 that teprotumumab led to hearing damage in 80% of treated individuals in a prospective study.6,7 Perhaps this is one of the reasons why EMA approval has not yet been granted.
- Szelog J. et al. (2022). Thyroid Eye Disease. Mo Med. 2022 Jul-Aug;119(4):343-350.
- In German Only: https://deutsch.medscape.com/artikelansicht/4909943#vp_2
- 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).
- In German Only: https://www.arzneimitteltherapie.de/heftarchiv/2020/04/aktuelle-meldungen-der-arzneimittelzulassungs-und-pharmakovigilanzbehoerden.html
- In German Only: https://biermann-medizin.de/morbus-basedow-neue-leitlinie-empfiehlt-doppeltherapie/
- In German Only: https://blog.endokrinologie.net/teprotumumab-basedow-hoerschaeden-4997/
- In German Only: Abstract No. 22 auf dem 90. ATA-Kongress, präsentiert am 3. Oktober 2021. Based on: Nancy A. Melville: Hearing Dysfunction With New Thyroid Eye Drug Is Common, Persistent.