Optical Coherence Tomography Angiography Findings in Deficiency Optic Neuropathy

ABSTRACT

A 44-year-old man was evaluated for bilateral progressive visual loss and diagnosed with vitamin B₁₂ deficiency optic neuropathy. Optical Coherence Tomography Angiography features of optic nerve and macula showed a decrease in peripapillary and macular vessel density that correlated well with the areas of retinal nerve fibre layer thinning seen on OCT. Further studies are needed to evaluate the role of this new technology in the evaluation of toxic and metabolic optic neuropathy.

Introduction

Optical coherence tomography angiography (OCTA) is a new non-invasive imaging technique that allows the estimation of the ocular vascular flow in real time. It is mainly used in the study of chorioretinal diseases such as diabetic retinopathy and choroidal neovascularization. Also, optic neuropathies are being investigated through this new tool as well, and microvascular alterations of the optic nerve head (ONH) are evident in ischaemic optic neuropathies and in other forms of optic neuropathy that are not primarily vascular diseases (e.g. demyelinating optic neuritis and compressive optic neuropathies). OCTA may help our understanding of the pathogenesis of these disorders. We describe a case of nutritional (deficiency) optic neuropathy in a young man from Africa, investigated by multimodal imaging in whom OCTA features correlated well with the involvement of the retinal nerve fibre layer at the level of the papillomacular bundle (PMB).

Case report

A 44-year-old man refugee from central Africa was evaluated for bilateral painless symmetrical progressive visual loss. Previous contrast enhanced brain and orbit magnetic resonance imaging was unremarkable. Genetic testing for Leber hereditary optic neuropathy and dominant optic atrophy were negative as was syphilis serology. At our examination best corrected visual acuity was 20/40 in both eyes (OU), pupils were equal with no relative afferent pupillary defect. Colour vision was affected bilaterally and the patient correctly identified only 4 out of 12 Ishihara colour plates in OU. Computerized visual field revealed a central scotoma OU and fundus examination was significant for optic nerve pallor temporally OU. Ganglion cell layer (GCL) was reduced centrally and in the PMB, and retinal nerve fiber layer (RNFL) thickness was bilaterally and symmetrically reduced in the temporal sector of the optic nerve (Figure 1). Vitamin B₁₂ levels were low at 90 ng/L (normal range is 180–914 ng/L). He was diagnosed with deficiency optic neuropathy (DON) and given intramuscular supplement of vitamin B₁₂ but was lost on follow-up and the primary cause was never ascertained. Swept-Source OCTA (Topcon DRI OCT Triton Plus®) with standard segmentation, was performed in order to study optic nerve and macula and the results compared to two normal controls (same refraction, age, sex and race). As compared to unaffected controls, a reduction of vascular density was evident at the level of the ONH (Figure 2) and PMB (Figure 3). Also, macular analysis (6mm x 6mm) showed vessel density attenuation in the entire area, especially in the foveal avascular zone that was enlarged in DON as compared to normal controls (Figure 4). No difference was evident at the level of choriocapillaris between the patient and normal control.

Figure 1.

Top. Retinography shows temporal pallor of the optic nerve. Middle. Computerized visual field test is consistent with a central scotoma in OS> OD. Bottom. Macular and optic nerve analysis shows reduced RNFL thickness in the temporal quadrant of the optic nerve and reduced GCL thickness in both eyes.

Figure 2.

Colour map of the optic nerve head. Perfusion colour-coded vessel density is reduced at the level of the optic nerve head (arrows) in the patient (top row) as compared to normal control (bottom row). Note marked reduction of vessel density at the papillomacular bundle (arrowhead).

Figure 3.

Colour map of the macula. Perfusion colour-coded topographic map shows vessel density diffusely reduced in the macula of the patient (top row) as compared to control (bottom row).

Figure 4.

Top row. Superficial macular capillary plexus of the patient shows enlarged foveal avascular zone and reduced capillary density as compared to normal control (bottom row).

Discussion

OCTA is a recently introduced non-invasive imaging technique that generates volumetric angiography images^1,2 without the use of dye. Fluorescein angiography (FA) and indocyanine green angiography remain the gold standard to study and classify most of the retinal and choroidal diseases, but their use is limited in optic nerve disorders. OCTA, on the contrary, may provide information concerning the peripapillary capillary network³, and the papillary microvasculature in general so that it may help our understanding of ONH disorders. OCTA has already been used for the study of microvascular changes in glaucomatous and ischaemic optic neuropathies but, at our knowledge, not yet in DON. The latter is characterized by bilateral symmetric painless progressive visual loss associated to central scotoma and optic disc pallor.⁴ The diagnosis of DON should be suspected in individuals who are malnourished or have a primary or secondary malabsorption problem. However, the optic neuropathy of pernicious anaemia and dietary vitamin B₁₂ deficiency can occur in seemingly healthy individuals without obvious symptoms or signs of nutritional deficiency.⁵ The differential diagnosis of DON is broad: certain maculopathies may present with silent fundus but mainly hereditary optic neuropathies and compressive lesions should be excluded. The role of OCTA in DON is still unknown, but this new tool might improve our understanding about the pathogenesis of optic nerve disorders caused by toxic exposure and nutritional/metabolic dysfunction even if they are not primarily vascular diseases. Our case shows interesting features of vascular alterations of ONH (Figure 5) and macula. These are probably secondary microvascular changes reflecting the reduction of RNFL/GCL thickness, more evident at the level of the PMB. A recent interesting article by Chen et al.⁶ highlighted the retinal OCTA features in chronic optic neuropathies. The authors retrospectively evaluated OCT angiography in 10 patients with different chronic optic neuropathies, and found that all of them showed a decrease in peripapillary vessel density on OCT angiography, regardless of the aetiology of the optic neuropathy. The peripapillary vessel loss on OCT angiography correlated well with the areas of retinal nerve fibre layer thinning seen on OCT. This finding is in line with our case, in which the vessel density loss well matched with the nerve fibre layer thickness reduction. Moreover we studied the macular OCTA findings and not only the peripapillary area, and found that also at macular level the vessel density was reduced in the affected patient as compared to normal controls. FA has been shown to demonstrate decrease of the microvascular bed in the ONH in atrophic nerves from any cause, but OCTA has a few advantages over FA. It is a noninvasive technique that also allows a manual, customized segmentation of the scansion level. All available machines are able to perform a standard OCT of the macula and ONH in the same exam, and many of them are also capable of ganglion cell complex analysis. Moreover the macular analysis is also available and the results (reduction of the vessel density in the PMB) are more evident in OCTA than in FA. We agree with Chen et al. that loss of the peripapillary capillary network in chronic optic neuropathies spatially corresponds to locations of RNFL thinning seen on standard OCT and that this finding is a result of the RNFL damage rather than the primary cause. The same mechanism may be applied to the PMB, as GCL loss that occurs in DON is more evident at this level. In conclusion, although the (differential) diagnosis of DON in mainly clinical, OCTA of the ONH and macula highlights interesting microvascular abnormalities of this uncommon clinical entity. A larger series of eyes with DON is needed to understand a possible prognostic value of OCTA features, i.e. if a reduced microvascular density of macula and ONH might influence visual recovery. It would be intriguing to find out if multimodal imaging (including OCTA) could help in the early differential diagnosis between nutritional optic neuropathy and chiasmal compression, the differential diagnosis of which may be difficult in some cases. To the authors’ knowledge this is the first case report in the English literature of macular and optic nerve OCTA features in a case of DON.

Figure 5.

OCTA of the ONH. Left from right: OCT angiography of nerve head, vitreous, radial peripapillary capillaries, choroid/disc. A reduction of vessel density is evident at all levels in the affected patient (A,C) compared to control (B,D). In the right column (choroid/disc level) note vessel density reduction at the level of the cup of the disc in the affected eye (arrows) as compared to unaffected control (dotted arrows).