thyroid eye disease ( ted ) is a chronic inflammatory disease of the eye that can occur in patients with systemic thyroid disorder .
it is the most common cause of bilateral and unilateral proptosis with a female preponderance and peak incidence in the 5th decade of life.1 ) although thyroid ophthalmopathy is not uncommon , its pathogenesis has not been thoroughly studied and remains unclear .
a consistent pathogenic link between graves ' disease and ophthalmopathy has yet to be identified.2 ) the pathogenesis involves immunoglobulin g antibody and an organ - specific autoimmune reaction .
t - cell lymphocytes and thyroid follicular cells with shared antigenic epitopes are thought to react in the retro - orbital space .
sight - threatening compressive optic neuropathy is one of the most feared complications of thyroid ophthalmopathy .
however , the occurrence of optic neuropathy is rare and constitutes about 4% to 8% of all complications.34 ) management of thyroid eye disease is based on the consensus statement produced by the european group on graves ' orbitopathy .
thyroid eye disease is usually self - limiting ; its frequency is declining ; and 3% to 5% cases are sight threatening.5 ) treatment for graves ' disease is directed towards alleviating symptoms , managing hyperthyroidism , and addressing issues such as smoking and other aggravating factors .
the following cases illustrate the atypical and subtle presentations of sight - threatening thyroid eye disease that can be missed during an initial visit .
they also illustrate the worsening of thyroid eye disease and its relationship to radioactive iodine ( rai ) therapy .
a 67-year - old malay man presented with gradual onset of bilateral eye redness and tearing for 2 months after receiving a second rai therapy for thyrotoxicosis without oral steroid coverage .
ocular examination revealed a poor visual acuity of 6/60 and n24 bilaterally with an absence of relative afferent pupillary defect ( rapd ) .
extraocular muscle examinations revealed generalized restriction in all positions of gaze particularly on downgaze ( figure 1 ) .
anterior segment examination of both eyes revealed fullness and redness of the eyelids , both of which appeared ptotic .
conjunctival injection and chemosis , as well as caruncle swelling and redness were also present .
there were minimal nuclear sclerosis cataracts present bilaterally and intraocular pressures were normal in both the primary gaze and upgaze .
further color vision , hess chart , binocular single vision , and bjerrum visual fields tests were performed , all of which revealed a derangement of color vision with d15 testing and constricted visual fields consistent with aspects of compressive optic neuropathy in both eyes . magnetic resonance imaging ( mri ) of the orbit ( figure 2 ) revealed crowding of the orbital apex consistent with thyroid ophthalmopathy .
a thyroid function test revealed that the patient , although taking oral thyrosine , was biochemically hypothyroid .
the patient was admitted , and a regimen of high - dose pulse intravenous methylprednisolone was commenced . after the fourth week of treatment , his visual acuity improved to 6/9 bilaterally , and a gradual resolution of the clinical signs and symptoms of thyroid eye disease was noted ( figure 3 ) . a 48-year - old malay woman presented with diplopia on upward gaze for 2 months following rai therapy without oral steroid coverage for her thyrotoxicosis .
she was newly diagnosed with thyrotoxicosis 4 months prior to the rai therapy . upon presentation ,
ocular examination of the right eye revealed a visual acuity of 6/36 , 6/12 with a pinhole occluder , and a near vision of n36 , while examination of the left eye revealed a visual acuity of 6/12 with a pinhole occluder and a near vision of n6 .
both eyes appeared proptosed , and extra - ocular muscle examination revealed restrictions in all gaze positions , especially in the upgaze ( figure 4 ) .
anterior segment examination revealed conjunctiva chemosis and injection particularly at the site of recti - muscle insertion .
nuclear sclerosis cataracts affecting the patient 's vision were present bilaterally , and were more pronounced over the right eye .
her intraocular pressures ( iop ) were high in both the primary gaze and upgaze .
fundus examination revealed a slightly hyperemic and swollen superior edge of the right optic disc , while the optic disc over the left eye was normal .
binocular single vision testing revealed diplopia at all gazes except the inferior gaze ( figure 5 ) .
hess chart , color vision , and bjerrum visual field tests were normal . computed tomography of the orbit with contrast showed a crowding of the right orbital apex with hypertrophy of all the extraocular muscles .
these results are consistent with thyroid ophthalmopathy . considering the clinical evidence for optic neuropathy ,
a 67-year - old malay man presented with gradual onset of bilateral eye redness and tearing for 2 months after receiving a second rai therapy for thyrotoxicosis without oral steroid coverage .
ocular examination revealed a poor visual acuity of 6/60 and n24 bilaterally with an absence of relative afferent pupillary defect ( rapd ) .
extraocular muscle examinations revealed generalized restriction in all positions of gaze particularly on downgaze ( figure 1 ) .
anterior segment examination of both eyes revealed fullness and redness of the eyelids , both of which appeared ptotic .
conjunctival injection and chemosis , as well as caruncle swelling and redness were also present .
there were minimal nuclear sclerosis cataracts present bilaterally and intraocular pressures were normal in both the primary gaze and upgaze .
further color vision , hess chart , binocular single vision , and bjerrum visual fields tests were performed , all of which revealed a derangement of color vision with d15 testing and constricted visual fields consistent with aspects of compressive optic neuropathy in both eyes . magnetic resonance imaging ( mri ) of the orbit ( figure 2 ) revealed crowding of the orbital apex consistent with thyroid ophthalmopathy .
a thyroid function test revealed that the patient , although taking oral thyrosine , was biochemically hypothyroid .
the patient was admitted , and a regimen of high - dose pulse intravenous methylprednisolone was commenced . after the fourth week of treatment , his visual acuity improved to 6/9 bilaterally , and a gradual resolution of the clinical signs and symptoms of thyroid eye disease was noted ( figure 3 ) .
a 48-year - old malay woman presented with diplopia on upward gaze for 2 months following rai therapy without oral steroid coverage for her thyrotoxicosis .
she was newly diagnosed with thyrotoxicosis 4 months prior to the rai therapy . upon presentation ,
ocular examination of the right eye revealed a visual acuity of 6/36 , 6/12 with a pinhole occluder , and a near vision of n36 , while examination of the left eye revealed a visual acuity of 6/12 with a pinhole occluder and a near vision of n6 .
both eyes appeared proptosed , and extra - ocular muscle examination revealed restrictions in all gaze positions , especially in the upgaze ( figure 4 ) .
anterior segment examination revealed conjunctiva chemosis and injection particularly at the site of recti - muscle insertion .
nuclear sclerosis cataracts affecting the patient 's vision were present bilaterally , and were more pronounced over the right eye . her intraocular pressures ( iop ) were high in both the primary gaze and upgaze .
fundus examination revealed a slightly hyperemic and swollen superior edge of the right optic disc , while the optic disc over the left eye was normal .
binocular single vision testing revealed diplopia at all gazes except the inferior gaze ( figure 5 ) .
computed tomography of the orbit with contrast showed a crowding of the right orbital apex with hypertrophy of all the extraocular muscles .
these results are consistent with thyroid ophthalmopathy . considering the clinical evidence for optic neuropathy ,
therefore , detection of this condition during clinical examination is highly important so that it can be efficiently managed .
progression of ophthalmopathy was more common in patients treated with rai than in those who received anti - thyroid drugs or surgery.16 ) one study proposed that the development or progression of ophthalmopathy after rai therapy may be related to the release of thyroid antigens as a result of radiation injury and to the subsequent enhancement of autoimmune responses directed toward antigens shared by the thyroid and orbit.7 ) rai for graves ' hyperthyroidism was followed by the development , or more often , the progression of ophthalmopathy in patients treated with rai alone , but not in those treated with rai and prednisolone.8 ) in these two cases , both patients were not administered oral steroids prior to or during rai therapy . in case 1 , the patient 's eyes appeared not proptosed , but ptotic .
there was evidence of optic neuropathy confirmed by constriction of the visual field , and mri of the orbit showed crowding of the orbital apex due to enlargement of the extraocular muscles .
this pathogenesis is due to the accumulation of glycosaminoglycans , which leads to a retention of water , increasing the intraorbital soft tissue volume and pushing the eye forward , resulting in proptosis .
therefore , the absence of proptosis in active ted increases the risk of optic nerve compression , because the swollen soft tissue within the confined space of the orbit prevents forward decompression of the optic nerve .
diagnosis of optic nerve dysfunction might be missed if there is no obvious proptosis as highlighted in case 1.9 ) it also stated that an increase in orbital pressure will precipitate dysthyroid optic neuropathy when there is lack of proptosis .
the lack of rapd detection may suggest that there was equal and bilateral involvement of the optic nerves by compression . in case 2 , both eyes appeared proptosed and there was grade 1 rapd over the left eye with secondary high iop in both eyes .
the subtle signs of optic neuropathy must be detected quickly , so that a treatment plan can be initiated to prevent further vision loss .
both patients were treated with 500 mg pulse intravenous methylprednisolone for 6 weeks and then 250 mg once weekly for another 6 weeks ( total period of 12 weeks with total dose of 4,500 mg ) .
this treatment regime was adapted according to the recommendation by kahaly et al.10 ) in patients receiving radiotherapy for ted , modifying the treatment can slow the development of ophthalmopathy.2 ) the administration of glucocorticoids prior to rai is generally expected to limit the progression of ophthalmopathy.11 ) in conclusion , active thyroid eye disease often presents as pseudoptosis instead of the classical lid retraction with ' starry ' gaze ( kocher sign ) .
although rai therapy is one of the primary treatment modalities for ted , it can also have a disastrous effect on the vision .
therefore , it is imperative for the patient to be administered glucocorticoids prior to treatment with rai for hyperthyroidism . family medicine practitioners and physicians need to anticipate the possibility for the development or worsening of thyroid eye disease post - rai treatment , as timely intervention can prevent the vision loss that results from compressive optic neuropathy in active thyroid eye disease .
 in patients with thyroid disease , ocular involvement or thyroid ophthalmopathy is common , irrespective of their thyroid status . a common feature of thyroid eye disease is eyelid retraction , which leads to a classical starry gaze ( kocher sign ) . 
 treatment with radioactive iodine ( rai ) is a known therapy for hyperthyroidism . 
 however , this treatment may lead to or worsen thyroid ophthalmopathy . 
 we report a case series of two patients with thyrotoxicosis , who presented with an atypical and subtle occurrence of thyroid eye disease ( ted ) soon after rai therapy . 
 one of the patients was initially diagnosed and treated for dry eyes ; however , over a period of time , the patient 's vision progressively deteriorated . 
 clinical and radiological investigations confirmed thyroid ophthalmopathy with low serum thyroid hormone levels . 
 both patients recovered well after immediate intensive intravenous steroid treatment . 
 these cases highlight the importance of recognizing partial ptosis as one of the presenting signs of active ted among general practitioners and physicians . 