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Simulate Leber congenital amaurosis (LCA) — the most severe group of inherited retinal dystrophies, presenting at birth or within the first year of life with profound visual impairment, nystagmus, and near-extinguished full-field electroretinogram (ERG). LCA is genetically heterogeneous, caused by mutations in more than 25 genes encoding proteins critical to photoreceptor or retinal pigment epithelium (RPE) function: RPE65 (visual cycle isomerase — LCA2, the first LCA gene approved for gene therapy), CEP290 (centrosomal protein 290 — LCA10, the most commonly mutated gene, responsible for ~15–20% of all LCA cases, involving a deep-intronic splicing mutation c.2991+1655A>G that creates a cryptic exon), GUCY2D (retinal guanylate cyclase 1 — LCA1, phototransduction cGMP synthesis defect, often with remarkable preservation of photoreceptor structure despite functional loss), AIPL1 (aryl hydrocarbon receptor interacting protein-like 1 — LCA4, chaperon for PDE6 assembly), RPGRIP1 (RPGR-interacting protein 1 — LCA6, photoreceptor connecting cilium), and CRB1 (crumbs homologue 1 — LCA8, outer limiting membrane integrity). The Franceschetti oculo-digital sign (eye poking/pressing) is a classical behavioural feature. RPE65+associated LCA (LCA2) is the only form with an approved gene therapy: voretigene neparvovec (LUXTURNA, Spark Therapeutics / Novartis, US FDA approved 2017), which delivers a functional RPE65 copy to RPE cells via subretinal AAV2 injection, restoring the visual cycle and enabling meaningful vision improvement. Model three LCA genetic subtypes: RPE65-associated LCA (visual cycle block, gene therapy responsive), CEP290/ciliopathy LCA (most common, deep-intronic mutation, antisense oligonucleotide research), and GUCY2D LCA (phototransduction cGMP deficit, structurally preserved photoreceptors). Inspect ΔE colour shift, CIE xy chromaticity, and image-level simulation of severe congenital visual loss.

Leber congenital amaurosis colour science simulation by Auric Artisan.

Base color
LCA subtype & settings
Severity / retinal degeneration 50%
Image simulation
Upload JPG/PNG (max 1200 × 1200). See how a scene appears through RPE65 visual cycle failure, CEP290 ciliopathy pan-photoreceptor loss, or GUCY2D phototransduction block with structural preservation.
Research notes
Leber congenital amaurosis was first described by Theodor Leber in 1869 as congenital amaurosis with nystagmus. It represents the most severe group of inherited retinal dystrophies — responsible for 10–18% of childhood blindness. LCA is genetically heterogeneous: 25+ causative genes encode proteins involved in retinoid processing (RPE65, LRAT, RDH12), photoreceptor cilia (CEP290, RPGRIP1, IQCB1), phototransduction (GUCY2D, AIPL1), photoreceptor structure (CRB1, TULP1), and transcriptional regulation (CRX, OTX2). The RPE65 c.271C>T p.Arg91Trp variant is among the most common RPE65 mutations. LCA10 (CEP290 c.2991+1655A>G) accounts for approximately 15% of all LCA. The 2017 FDA approval of voretigene neparvovec (LUXTURNA) for RPE65-associated LCA marked the first gene therapy for an inherited retinal disease to receive regulatory approval.
Swatches
Normal
HEX: — • RGB: — • xy: —
LCA affected
HEX: — • RGB: — • xy: —
ΔE (CIE76)
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ΔE (CIEDE2000)
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Deep preview
Normal
LCA (deep)
Chromaticity (CIE xy)
Pan-photoreceptor loss chromaticity shift toward D65
D65 white point: 0.313, 0.329
Image simulation

Leber congenital amaurosis simulations model the near-complete photoreceptor functional loss of LCA using a gene-subtype-dependent photoreceptor channel weight model in the sRGB colour space. RPE65-associated LCA models a blocked visual cycle (11-cis-retinal depletion) as severe pan-photoreceptor attenuation with relative preservation of photoreceptor structure — reflecting the RPE65 paradox of structurally intact but functionally silent rods and cones. CEP290/ciliopathy LCA models progressive pan-photoreceptor degeneration from ciliary dysfunction (loss of outer segment disc renewal), expressed as near-complete luminance and colour signal loss. GUCY2D LCA models the cGMP-driven constitutive photoreceptor depolarisation as severe functional loss despite relatively preserved anatomy. ΔE2000 per Sharma et al. (2005). Not for clinical diagnosis — LCA requires genetic panel testing (25+ genes), full-field ERG, and paediatric ophthalmic examination. Any child with poor visual behaviour from birth, nystagmus, or eye-poking requires urgent paediatric ophthalmology evaluation.

Multi-condition comparison
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Compare RPE65 visual cycle block, CEP290 ciliopathy pan-degeneration, and GUCY2D phototransduction deficit stages. Image simulation applies severe luminance and colour signal loss modelling profound congenital photoreceptor dysfunction.