Sudden mono-ocular blindness with recurrent transient diplopia and ptosis in a middle-aged woman

Abstract

Sudden painless loss of vision is an ophthalmologic and a medical emergency resulting from various causes such as occlusion of retinal artery or vein, macular or vitreous haemorrhages, retinal detachment, and anterior and posterior ischaemic optic neuropathy. We report a 48-year-old woman presenting with right monocular blindness due to branch retinal artery occlusion whose vision recovered due to timely paracentesis coupled with treatment with adequate antiplatelet agents and anticoagulants. The patient had transient diplopia and ptosis despite adequate antiplatelet agents and anticoagulants. Thorough search for aetiology revealed the underlying cause to be aortoarteritis. Aortoarteritis is a rare disease, and ocular involvement occurs late in the disease. We review ophthalmologic manifestation of aortoarteritis and diagnostic utilities of various modalities for aortoarteritis.

Background

We intend to stress on the meticulous evaluation and management of uniocular vision loss to rule out the underlying medical condition. A patient of retinal artery occlusion was thoroughly investigated and finally diagnosed of having Takayasu’s aortoarteritis (TA) with multiple diagnostic dilemmas in the process.

Management of retinal artery occlusion on the war footing is intended here to salvage the vision. Simple means like posterior chamber paracentesis in resource-limited settings as done in our patient can be immensely useful to prevent vision loss. Our patient improved drastically and her vision restored to near normal. Further branched retinal artery occlusion occurring as a complication due to aortoarteritis is extremely rare but still such a complication should be kept in mind. We faced difficulty in diagnosis as the MR angiography of the patient was inconclusive leading us to use ¹⁸FDG PET-CT to confirm the same. Trends in recent times have shifted from the use of more invasive conventional angiography to less invasive imaging modality, like CT or MR angiography; yet, in some cases like ours, the MR angiography fails to pick up the aortoarteritis and hence remains inconclusive. Consequently, newer imaging options like ¹⁸FDG PET-CT can be immensely useful in such cases to pick up inflammation and plan further management. We strongly support this upcoming modality in such diagnostic dilemmas.

Case presentation

A 48-year-old married woman presented to the emergency medical services of a tertiary hospital with sudden onset painless loss of vision in the right eye involving the right inferotemporal quadrant of half-hour duration. She also complained of episodic right hemicranial headache for the past 2 months. There was no history of aura, jaw claudication or sensory-motor deficit. A week ago, she had transient diplopia lasting for a few hours followed 2 days later by monocular vision loss in the right eye lasting for 15 min. Her ophthalmologic, neurologic examination and MRI brain at that time were reported to be normal.

In the past, she was diagnosed to be hypertensive at the age of 38 years and was on losartan 50 mg daily until recently when her family physician added atenolol 50 mg for recent increase in her blood pressure. Headache was attributed to the recent rise in blood pressure. At the age of 42, she was subjected to right iliac artery stenting at some other centre in view of right lower limb claudication of 1 year duration when angiography of lower limbs revealed 90% block in right iliac artery. Laboratory tests at that time were normal except for an erythrocyte sedimentation rate (ESR) of 86 mm at 1 h. She was not on any antiplatelet agents or anticoagulants. In 2005, at the age of 44 she had reported to our rheumatology services for pain in small joints of hands of 1-week duration. There was no history of fever, rash, Raynaud’s, preceding dysentery or urinary tract infection. Systemic examination revealed tenderness at bilateral second and third metacarpophalangeal joints. Non-steroidal anti-inflammatory drugs were used for treatment and she improved within 2–3 weeks. Biochemical investigations, lipid profile and urine examination at that time were normal, and antinuclear antibody (ANA) and rheumatoid factor were absent. Hepatitis B and C serology was negative. She was c-ANCA positive, but anti-PR3 negative, and anticardiolipin antibodies were positive, IgM 64 and IgG 50 GPU. She was labelled to have a probable anti-phospholipid antibody syndrome and was offered anticoagulation, which she declined, and she was lost to follow-up.

On examination, she was a well-maintained middle-aged lady with normal vitals. Right femoral, posterior tibial and dorsalis pedis were feeble. Bilateral carotids were well felt but there was a bruit over the right carotid artery. Blood pressure was 140/84 mm Hg in both upper limbs. Systemic and rheumatological examination was normal. Temporal arteries were not tender. Visual acuity in the left eye was 6/6 and in the right eye was 6/24. There was a relative afferent papillary defect in the right eye with reduced corneal sensations.

Right funduscopic examination revealed a superior temporal quadrant branched retinal artery occlusion with fragmented blood column with an evident embolus. There was macular oedema with foveal splitting without any hypertensive changes (figure 1). She was given 300 mg of aspirin and 0.6 mg of subcutaneous low-molecular weight heparin (LMWH), after collecting blood for procoagulant state tests and serology. Urgent ophthalmology consultation was obtained.

Figure 1.

Right funduscopic image showing a superior temporal quadrant BRAO with fragmented blood column with an evident embolus near the bifurcation. Associated macular oedema with foveal splitting without any hypertensive changes is seen.

Investigations

Her present lab tests were haemoglobin, 10.8 g/dl; white cells, 4800/mm³; ESR, 56 mm/h; C reactive protein (CRP), 8.2 mg/l; creatinine, 1 mg/dl; total cholesterol, 204 mg/dl (low-density lipoprotein, 102; high-density lipoprotein, 42); and triglycerides, 148 mg/dl. ANA and antineutrophil cytoplasmic antibody (ANCA) were negative. HIV, VDRL, HBsAg and anti-HCV serology was negative. Anticardiolipin antibodies were negative from two different labs. Her 2D ECHO of the heart was normal. Carotid Doppler revealed absent waveform on right internal carotid artery from its origin with a normal left carotid, while MR brain with angiography showed 100% block of right internal carotid artery at its origin. Temporal artery biopsy was normal.

Differential diagnosis

Branched retinal artery occlusion with suspected underlying cause as TA, antiphospholipid antibody syndrome or temporal arteritis.

Treatment

Within 4 h of presentation, she was subjected to anterior chamber paracentesis by the ophthalmologist, which led to dislodgement of the embolus to peripheral retinal vessels (figure 2) with improved retinal perfusion and subjective improvement in vision by 30%. For reducing the retinal oedema, she was given intravenous methylprednisone 1 g for 3 days followed by oral steroids 1 mg/kg/day. Other medications included LMWH 0.4 mg subcutaneous twice daily, aspirin 75 mg and clopidogrel 75 mg.

Figure 2.

Right funduscopic image after anterior chamber paracentesis showing dislodged embolus, improved retinal perfusion and subsiding macular oedema.

Outcome and follow-up

As inflammatory markers were persistently high since 2003, aortoarteritis was suspected. Contrast-enhanced MR aortography of the entire aorta was performed using 3D-SPGR after intravenous gadolinium DTPA. 3D MIPs’ axial and coronal reformations were obtained. It was reported as follows: ‘The ascending arch and descending thoracic aorta were normal in calibre and their wall were smooth, both carotids, brachiocephalic, origins of both subclavians were normal. There was mild short segment narrowing of 3rd part of the left subclavian artery. The abdominal aorta was normal in calibre with mild eccentric thickening of left lateral wall of abdominal aorta at level of renal arteries. Renal arteries and superior mesenteric arteries were normal. There was mild short segment narrowing of origin of Ciliac artery. Stent was seen in right common iliac artery with good distal flow.’ The radiologist’s opinion was that this report was not consistent with the diagnosis of aortoarteritis. While on dual antiplatelet agents and LMWH on the sixth day, she developed ptosis of the right eye, which improved spontaneously within 4 h. Warfarin was added. Interventional radiologist advised digital subtraction angiography or a conventional angiography for a detailed study of origin and lumen of the right internal carotid artery. But considering a possible risk of thromboembolism involved in the procedure and also the need for stopping warfarin prior to the procedure, angiography was not done. Instead ¹⁸FDG PET-CT scan was performed on the 15th day. It revealed evidence of active inflammation in aorta and its branches suggestive of active aortoarteritis (figure 3). The linear pattern of abnormality did not favour thrombi. Oral prednisolone 1 mg/kg/day and oral methotrexate 15 mg/week were continued. At 2-week follow-up visit, the patient reported 60% subjective improvement in her vision, and a well-controlled hypertension now requiring only one antihypertensive, losartan 50 mg/day, and relief of headache. At 12-week follow-up, the patient reported 80% subjective improvement in vision, CRP 3.4 mg/l (normal: 0–6) and blood pressure controlled on 25 mg losartan. PET/CT at 12 weeks revealed a decrease in the inflammatory activity in almost all the previously seen arteries (aorta and its branches) without involvement of any new arterial region suggesting favourable response to therapy.

Figure 3.

¹⁸FDG PET-CT images – sagittal view shows diffuse increased uptake of FDG in entire aorta with few focal active sites in the thoracic part of descending aorta.

Discussion

TA is a granulomatous pan-arteritis affecting the aorta and its branches, with onset before 40 years of age. It is most prevalent in adolescent girls and young women in their 30s with female:male occurrence of 8:1. Clinical presentations are related to compromised blood flow to the vessel involved. Common presenting features are hypertension in the young (32–93%), peripheral and visceral claudication (17–93%), cerebrovascular events (58%) and pyrexia of unknown origin (33%).¹ It occurs in three stages: (1) early systemic stage, (2) vascular inflammatory stage and (3) stage of fibrosis. By the time pulseless disease sets in, the disease is in the stage of fibrosis. In one third of the patients, the arch of aorta is involved leading to ischaemic symptoms in the cerebral and ocular circulation and the upper limbs. Involvement of the aorta is patchy with normal vessel between lesions.

Eye involvement occurs late and is reported in up to 35% of patients with 8% presenting as transient vision loss.¹ Takayasu, a Japanese ophthalmologist, after whom the disease is named was the first to describe a 21-year-old female patient with loss of vision and a wreath-like vascular anastomosis of retinal vasculature surrounding the optic disc in 1908. The ocular features in TA occur late resulting from the ocular hypoperfusion secondary to obliteration of carotid arteries and its branches. Classical features of Takayasu retinopathy were described by Uyama and Asayama in 1976² as ischaemic retinopathy with dilatation of small vessels (stage I), capillary microaneurysm formation (stage II), arteriovenous anastomosis (stage III), and further ocular complications as neovascularisation, retinal and vitreous haemorrhage, retinal detachment, secondary cataract and glaucoma (stage IV). Hypertensive retinopathy and anterior ischaemic optic neuropathy are also described in aortoarteritis. Patients can present with amaurosis fugax (CRAO, BRAO), sudden onset painless vision loss (retinal or vitreous haemorrhage), progressive painless (cataract) or painful (angle closure glaucoma) diminution of vision, diplopia and ptosis (due to ischaemia of extraocular muscles).

Branched retinal artery occlusion is rare in TA with only few reported cases.^3–5 Branch retinal artery occlusion (BRAO) is an ophthalmic emergency with measures directed to re-perfuse the hypoxic retina within the retinal tolerance time after which irreversible ischaemic damage is seen. Retinal tolerance time as in primates was 105 min⁶ whose extrapolation to humans ranged from 24⁷ to 48 h.⁸ However, shorter the occlusion time, better is the eventual visual recovery with the prognosis being directly proportional to the visual acuity at presentation.⁹ Various treatment modalities like dilatation of retinal artery (sublingual isosorbide dinitrate, carbogen inhalation), physical removal of obstruction (by ocular massage), reduction of intraocular pressure (anterior chamber paracentesis, intravenous acetazolamide or mannitol), thrombolysis (intravenous or local intra-arterial thrombolysis, Nd:YAG laser), antiplatelets (aspirin, clopidogrel), anticoagulation (LMWH and warfarin) and thrombolysis by low-dose (50 mg) recombinant tissue plasminogen activator¹⁰ have been tried with varying success rates. Anterior chamber paracentesis needs expertise. Its availability improved vision in our patient.

Conventional catheterisation angiography is considered the gold standard technique but is invasive. Intravenous digital subtraction angiography and CT contrast angiography is a less invasive option but it fails to depict early stages of disease like aortic wall thickness and irregular outline of the descending thoracic aorta.¹¹ MR angiography is claimed by some to show early arterial wall thickening involving the aorta and major branches by using spin echo T1-weighted images and bright signals indicative of oedema in and around the inflamed vessels on T2-weighted images. Reports on sensitivity of MR aortography in the diagnosis of aortoarteritis are variable. In a case series assessing the role of MR angiography in aortoarteritis, signs of vessel wall oedema were demonstrated in more than 50% of all patients in whom Takayasu arteritis was judged to be clinically inactive or of uncertain activity status.¹² Gadolinium contrast reveals significant enhancement in and around the aorta and carotid arteries in the acute and chronic phase.¹³ A prospective blinded study at the National Institutes of Health in 10 patients of aortoarteritis reported that MR aortography (using 0.5-T MRI scan) had sensitivity of only 38% with patient-by-patient analysis and 54% with lesion-by-lesion analysis, thereby inferring that vascular imaging with MRI was inadequate in TA compared with angiography.¹⁴ In our patient on MR aortography, the entire thoracic aorta and abdominal aorta were normal but for a mild left lateral wall thickening of the aorta at the level of renal arteries. Narrowing at the origin of celiac artery and the third part of left subclavian was not considered significant enough by the radiologist for the diagnosis of aortoarteritis, though patchy involvement is known in aortoarteritis. Conventional aortography with cannulation of the carotid ostia to study the state of vessel wall and lumen as suggested by interventional radiologist was considered risky due to ongoing ischaemic events in right carotid territory.

¹⁸FDG PET-CT is a novel imaging method for the diagnosis of aortoarteritis where abnormal 18FDG uptake is seen in the walls of large vessels (>4 mm) if vascular inflammation is present. FDG uptake is related to both the metabolic rate of the cell and the abundance of glucose transporters. Principle advantage of ¹⁸FDG-PET is its ability to detect prestenotic disease in patients presenting with non-specific features commonly associated with early TA.^{15 16} In a case series of 12 patients of aortoarteritis, it showed sensitivity of 92% and specificity of 100% in diagnosis.¹⁷ Following adequate immunomodulatory therapy, reduction in uptake at the site of aortitis has been correlated with clinical improvement, reduction in acute-phase response and disease activity index, and a reduction in aortic wall thickness on angiography.^{17 18} In a recent study by Krishna et al,¹⁹ PET/CT confirmed Takayasu in 57% of patients who presented with peripheral vasculitis by demonstrating aortic involvement; it accurately identified responders and non-responders aiding the clinician in therapeutic decision and it confirmed active Takayasu disease in 87% of patients who were positive on morphological imaging PET/CT. Intense linear uptake of FDG is more characteristic of active vasculitis rather than atherosclerosis.

Our patient had hypertension at age 38, right iliac artery occlusion at age 42 and right monocular blindness, diplopia and ptosis at age 48. She had right carotid bruit. This could result from extensive atherosclerosis, thromboembolic phenomenon from the heart or aortoarteritis. Normal lipid profile in 2005 and 2009 ruled out atherosclerosis, though atherosclerosis affects the internal carotids and aortoarteritis involves the common carotids. Normal 2D echo examination of the heart ruled out heart as a source of recurrent embolisation. Her persistently high ESR made aortoarteritis a more likely possibility. Thus in our patient with ongoing disease activity, where conventional aortography was differed due to specific reasons, MR aortography failed to confirm the diagnosis of aortoarteritis and PET/CT was found to be an important diagnostic tool. It also correlated well with patient’s clinical improvement at 12 weeks.

Learning points.

• ▶Sudden monocular loss of vision needs to be dealt with utmost urgency.
• ▶Underlying rare medical conditions, like aortoarteritis, should be thought of and a thorough search should be carried out.
• ▶Simple OPD procedures, like posterior chamber paracentesis, done in time can save vision.
• ▶BRAO is an extremely rare and disastrous complication of aortoarteritis.
• ▶MR angiography is considered as a good alternative to the gold standard but invasive conventional angiography fails to pick up aortoarteritis in all cases. In such cases, novel modalities like ¹⁸FDG PET-CT can be crucial in arriving at the diagnosis.