A proposal for an updated staging system for LCHADD retinopathy

Abstract

Objective: To develop an updated staging system for long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency (LCHADD) chorioretinopathy based on contemporary multimodal imaging and electrophysiology.

Methods: We evaluated forty cases of patients with genetically confirmed LCHADD or trifunctional protein deficiency (TFPD) enrolled in a prospective natural history study. Wide-field fundus photographs, fundus autofluorescence (FAF), optical coherence tomography (OCT), and full-field electroretinogram (ffERG) were reviewed and graded for severity.

Results: Two independent experts first graded fundus photos and electrophysiology to classify the stage of chorioretinopathy based upon an existing published system. With newer imaging modalities and improved electrophysiology, many patients did not fit cleanly into a single traditional staging group. Therefore, we developed a novel staging system that better delineated the progression of LCHADD retinopathy. We maintained the four previous delineated stages but created substages A and B in stages 2 to 3 to achieve better differentiation.

Discussion: Previous staging systems of LCHADD chorioretinopathy relied on only on the assessment of standard 30 to 45-degree fundus photographs, visual acuity, fluorescein angiography (FA), and ffERG. Advances in recordings of ffERG and multimodal imaging with wider fields of view, allow better assessment of retinal changes. Following these advanced assessments, seven patients did not fit neatly into the original classification system and were therefore recategorized under the new proposed system.

Conclusion: The new proposed staging system improves the classification of LCHADD chorioretinopathy, with the potential to lead to a deeper understanding of the disease's progression and serve as a more reliable reference point for future therapeutic research.

Keywords: LCHAD deficiency; LCHADD; chorioretinopathy; staging.

Figure 1.

First row; fundus images representing from stage 1 to 4. Second row representing fundus autofluorescence start from speckle hypoautofluorescence mostly within vascular arcades in stage 2A progressing to nearly total dense hypoautofluorescence towards periphery in stage 4 (red arrow) third row demonstrates cross-sectional OCT scan of central macular area comparing each stages, severe attenuation of choroid was observed by OCT in stage 3B.(yellow arrow) fourth and fifth rows showing scotopic ERG and photopic ERG response respectively, amplitude of b wave gradually decline in more advance stages.