Spontaneous ophthalmic artery occlusion in children due to Hyperhomocysteinemia.

Ophthalmic artery occlusion usually presents as a sudden onset profound decrease in vision in the middle-aged and elderly patients following periocular procedures (retrobulbar injection/glabellar fat injection), embolism from the heart or after prolonged systemic surgery. In this report, we describe three children with spontaneous ophthalmic artery occlusion who presented with unilateral loss of vision and diagnosed elsewhere as optic atrophy whose detailed history and examination were suggestive of ophthalmic artery occlusion. Detailed systemic and laboratory evaluation revealed hyperhomocysteinemia as the only potential risk factor. To the best of our knowledge, this is the first report of the association of hyperhomocysteinemia and spontaneous ophthalmic artery occlusion.

Introduction

Ophthalmic artery occlusion is a rare, but blinding condition that accounts for about 2% of all the ocular vascular occlusions.[1] It usually affects the middle aged and elderly with cardiovascular disease,[1] however, rarely it has rarely been reported to affect the children and young adults (<50 years) secondary to retrobulbar corticosteroid injections,[2] intranasal corticosteroid injections,[3] autologous fat injections into the glabellar regions,[4] following embolism from the a left atrial myxoma[5] and as a complication of prolonged surgery under general anesthesia especially neuro/spinal surgery.[6] In a previous report, Ganesh et al. described spontaneous ophthalmic artery occlusion in a 7-year-old girl without any underlying etiology.[7] Hyperhomocysteinemia is reported as an independent risk factor for systemic and ocular vaso-occlusive disorders, including non arteritic ischemic optic neuropathy (NAION), central retinal artery occlusion (CRAO), and central retinal vein occlusion, isolated ischemic cranial nerve palsies, especially in young patients.[8] In this report, we describe three children with ophthalmic artery occlusion where hyperhomocysteinemia was the only risk factor. To the best of authors’ knowledge, this is the first report of this presumed association.

Case Report

Between November 2008 and October 2013, we saw a total of six patients with ophthalmic artery occlusion in our institute. Of these, three were children (<16 years of age at time of onset). Table 1 summarizes the presenting features, clinical features and laboratory results of these patients. Two patients were girls and one boy. The mean age of patients at the time of onset of a decrease in vision was 12 years (range: 8-14 years).

Table 1

Clinical and demographic features of the patients

Two patients presented to us with a history of unilateral decrease in vision and were diagnosed to have optic atrophy previously. In two patients, the duration of the onset of symptoms was 2 months, whereas in the third patient the diminution of vision dated back to 6 years. Anterior segment examination was normal in all patients except presence of relative afferent papillary defect in the affected eye. Detailed fundus examination in these patients showed a diffuse pallor of the optic disc with marked attenuation of arterioles and diffuse retinal pigmentary (RPE) changes, suggestive of a possible ophthalmic artery occlusion [Figure 1, from patient 1 and patient 3 as representative of all the three patients]. The other eye fundus examination was unremarkable. Magnetic resonance imaging brain (done elsewhere for the evaluation of optic atrophy) in all patients was within normal limits.

Figure 1

Color Fundus photograph (montage view) of the patient 1 (a) and patient 3 (b), showing the presence of diffuse disc pallor (asterisk), attenuated blood vessels (black arrows), diffuse retinal pigmentary changes (arrow heads) along the entire retina suggestive of left ophthalmic artery occlusion in these patients

All the three patients underwent investigations for any potential risk factors such as diabetes mellitus, hypertension, dyslipidemia, collagen vascular disorders, source of embolism (two-dimensional echocardiography and carotid Doppler), prothromboic disorders (bleeding time, coagulation time, protein C, protein S deficiency) and serum homocysteine levels.

The erythrocyte sedimentation rate, C-reactive protein, lipid levels, blood glucose levels, blood pressure, coagulation profile, two-dimensional echo and carotid Doppler were within normal limits.

However, all the three patients had elevated serum homocysteine levels. Mean serum homocysteine levels were 37.60 μmol/L (Range: 15.20-65.00 μmol/L, standard deviation: 25.3 μmol/L normal: 3.90-13.90 μmol/L, chemiluminescence method). All patients were further evaluated for Vitamin B12 and folic acid levels, which were found to be normal in all except one child where serum Vitamin B12 levels was 152 pg/ml (normal folic acid >5.38 ng/ml, Vitamin B12-211-911 pg/ml). This patient was evaluated by a hematologist and was found to have a dietary deficiency of Vitamin B12. Further genetic analysis for the mutations in homocysteine metabolism were contemplated but were not feasible due to lack of facilities.

Situation and guarded visual prognosis were explained to the parents. All the patients were treated with oral vitamin supplementation (Vitamin B6-250 mg, Vitamin B12-1500 μg and folic acid-5 mg/day) and oral antiplatelet therapy (aspirin, 75 mg/day). None of the patients developed any further episodes of ocular or systemic vaso-occlusion.

Discussion

This report highlights three young children with unilateral ophthalmic artery occlusion. It can be differentiated from CRAO by widespread attenuation of arterioles, RPE stippling and absence of cherry red spot [Table 2]. Ophthalmic/retinal vascular occlusion (RVO) suggested an underlying systemic disease and recommended workup of a patient with RVO is suggested in Table 3.

Table 2

Differentiating features between central retinal artery and ophthalmic artery occlusion

Table 3

Suggested work up of patients with retinal vascular occlusion

Hyperhomocysteinemia characterized by an elevation of serum homocysteine levels, is a potent atherosclerotic risk factor that promotes thrombus formation and increases the risk of vascular occlusion.

A 5 μmol/L elevation of homocysteine levels has been reported to increase the risk of vaso-occlusive diseases by 60% in males and 80% in females with an increased odds ratio of 1.4-1.7.[9]

It has been reported that as many as 60% of the patients with ischemic strokes and 17% of young patients with NAION may have isolated hyperhomocysteinemia as a risk factor.

Similar to the previous reports, patients in our series were also young with a mean age of 14 years (range: 12-16 years). In our series, all patients presented with ophthalmic artery occlusion without any history of surgery or other known risk factor apart from the hyperhomocysteinemia.

We have previously reported a case series of young patients with abducens nerve palsy and hyperhomocysteinemia and a case of combined cilioretinal artery obstruction and NAION in a young patient with hyperhomocysteinemia.

Hyperhomocysteinemia is a potentially modifiable risk factor. Dietary supplementation of 250 mg of Vitamin B6, 5 mg of folic acid and 1500 μg Vitamin B12, daily has been shown to lower serum homocysteine levels.

Although hyperhomocysteinemia has been reported with various vaso-occlusive diseases, a causal association was not proven. However, in a recent study, Al Wadani et al.[10] reported in the age and sex matched patient with retinal vein occlusion and controls showed the presence of hyperhomocysteinemia was a risk factor for the development of RVO in Indian population. Hence, the authors’ recommend investigating and treat for hyperhomocysteinemia in vaso-occlusive diseases like ophthalmic artery obstruction.

The main limitation of our series is its retrospective nature with limited size. However, this is an uncommon condition and to the best of our knowledge, this is the first reported association of hyperhomocysteinemia with spontaneous ophthalmic artery occlusion. Based on our findings we recommend estimation of serum homocysteine in the work-up of young patients with spontaneous ophthalmic artery occlusion in the absence of other risk factors.