Optical coherence tomography angiography of choroidal neovascularization in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD)

Abstract

Purpose: To report the clinical utility of optical coherence tomography angiography (OCTA) for demonstrating choroidal neovascularization (CNV) associated with Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency (LCHADD) retinopathy.

Methods: Thirty-three participants with LCHADD (age 7-36 years; median 17) were imaged with OCTA and the Center for Ophthalmic Optics & Lasers Angiography Reading Toolkit (COOL-ART) software was implemented to process OCTA scans.

Results: Seven participants (21 %; age 17-36 years; median 25) with LCHADD retinopathy demonstrated evidence of CNV by retinal examination or presence of CNV within outer retinal tissue on OCTA scans covering 3 × 3 and/or 6 × 6-mm. These sub-clinical CNVs are adjacent to hyperpigmented areas in the posterior pole. CNV presented at stage 2 or later of LCHADD retinopathy prior to the disappearance of RPE pigment in the macula.

Conclusion: OCTA can be applied as a non-invasive method to evaluate the retinal and choroidal microvasculature. OCTA can reveal CNV in LCHADD even when the clinical exam is inconclusive. These data suggest that the incidence of CNV is greater than expected and can occur even in the early stages of LCHADD retinopathy.

Keywords: CNV; Choroidal neovascularization; LCHADD retinopathy; Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency; OCT angiography.

Fig. 1

Patient 1 of LCHADD complicated with CNV in the right eye. A, Color fundus photograph revealing a nummular hyperpigmented lesion in the right macula with a scar temporal and superonasal to the pigmented lesion. B, Color fundus photograph of the same patient after 22 years follow up showing extension of the dense hyperpigmented lesion and faint scar surrounded by a pale macular choroidal atrophy. C, After applying the projection resolved algorithm to a 6 × 6 mm red box area in B, color-coded composite en face OCTA, subretinal choroidal neovascular plexus (yellow) was highlighted D, Cross-sectional Spectral Domain-OCTA image corresponding to the white dot line in C showing subfoveal choroidal neovascularization. E, En-face slab of choriocapillaris showing an enlarged area of subfoveal CNV network. F, En-face OCT slab of the photoreceptor demonstrated subretinal fibrotic scar. Retinal tubulation adjacent to the CNV were observed. (yellow arrow). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 2

Left column demonstrates a progression of the fundus changes in LCHADD in patient 2, starting at 6 years of age until 31 years of age. The retinal vessels are tortuous. RPE pigmentation is presented in the central fovea of both eyes. A peripapillary area of bare sclera has appeared and enlarged over time along with diminished pigment clumps in the central fovea in the left eye (non-affected eye). Finally, the bare sclera is visible over the whole posterior pole. Only a few large choroidal vessel trunks are seen in the center of the macula and temporal to it. Pigment clumping is persisted in the central macula of the right eye (affected eye). Red box delineates 6 × 6 mm area corresponding to OCTA images. The middle and right columns demonstrate OCTA images of CNV-associated LCHADD. A,B, En face OCTA slab at the choroidal layer and Ellipzoid zone of photoreceptor, showing the appearance of subfoveal choroidal neovascularization. C, Color composite en face OCTA of inner retinal vasculature (purple) and CNV vessels (yellow) in a circular pattern. D, Cross-sectional Spectral Domain-OCTA image corresponding to the white dot line in C showing type 2 neovascular membrane and pigment with relative flow (yellow) within the lesion. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 3

Patient 3 of LCHADD complicated by CNV OS. A, Fundus photo shows diffuse chorioretinal atrophy OU with white fibrotic scar and pigment clumping at macula OS, Red box delineates a 6 × 6 mm area corresponding to OCTA images. B, 6 × 6 mm OCTA in inner and outer retinal slab revealed the CNV plexus (yellow) C, En-face slab of choriocapillaris showing an enlarged area of CNV network. D, segmented cross-sectional scan of OCTA of white dot line in B demonstrates angiographic flow (yellow) within subretinal hyperreflective tissue of left eye. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 4

Patient 4 of CNV associated LCHADD. A, Fundus photo shows subretinal white scar at perimacular region in stage 2 LCHADD retinooathy OD, central choroidal atrophy and pigment clumping at macula OS from previous CNV. Red box delineates 6 × 6 mm area corresponding to B and C images. B, En-face 6 × 6 mm OCTA in outer retinal slab revealed the CNV plexus (yellow) C, Cross-sectional Spectral Domain-OCTA image at the white dot line in B showing type 1 neovascular membrane. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 5

A and B, patient 5 OD and OS respectively,C, patient 6 of CNV-associated LCHADD. First column is the fundus photographs of these two patients in advance stage, choroidal atrophy were observed in all cases with pigment clumping at macula OS in patient 6. Second column demonstrated En face OCTA slab of photoreceptors. Retinal tubulation were observed in difference patterns. (yellow arrow) Third column, en-face 6 × 6 mm OCTA in the outer retinal slab corresponding to area within the red boxes in column A revealed subretinal CNV plexus (yellow). The last column showed cross-sectional Spectral Domain-OCTA with color-coded flow overlay corresponding to white dot line in the third column, illustrated the angiographic flow of CNV (yellow). OCTA image of a bottom row from patient 6 revealed slightly low flow signal which possible a small CNV. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)