Correlation between photoreceptor layer integrity and visual function in patients with Stargardt disease: implications for gene therapy.
OBJECTIVE
To perform a clinical characterization of Stargardt patients with ABCA4 gene mutation, and to investigate the correlation between the inner and outer segment (IS/OS) junction morphology and visual acuity, fundus lesions, electroretinogram abnormalities, and macular sensitivity.


METHODS
Sixty-one patients with Stargardt disease (STGD) were given a comprehensive ophthalmic examination. Inner-outer photoreceptor junction morphology evaluated by spectral-domain optical coherence tomography was correlated with visual acuity, fundus lesions, fundus autofluorescence, full-field and multifocal electroretinography responses, and microperimetric macular sensitivities. We classified STGD patients into three groups: (1) IS/OS junction disorganization in the fovea, (2) IS/OS junction loss in the fovea, and (3) extensive loss of IS/OS junction. Mutation analysis of the ABCA4 gene was carried out by sequencing the complete coding region.


RESULTS
A significant difference in visual acuity was observed between IS/OS groups 1 and 2 and between IS/OS groups 2 and 3 (P < 0.0001). A significant difference in microperimetry sensitivity was observed between IS/OS groups 2 and 3, and between IS/OS groups 1 and 3 (P < 0.0001). There was also a statistically significant correlation between IS/OS abnormalities and the extent of fundus lesions (Spearman P ≤ 0.01), as well as with the type of ERG and multifocal ERG results (Spearman P ≤ 0.01). Finally, the degree of IS/OS junction preservation showed a statistically significant correlation with the extension of foveal abnormalities assessed by fundus autofluorescence imaging (Spearman P ≤ 0.01). The G1961E mutation was more frequent in the patients without extensive loss of IS/OS junction (P = 0.01) confirming its association with a milder STGD phenotype.


CONCLUSIONS
The results of this study suggest that a comprehensive approach in the examination of Stargardt patients has the potential to improve the understanding of vision loss and may provide a sensitive measure to evaluate the efficacy of future experimental therapies in patients with STGD.
Department of Ophthalmology, Department of General Pathology, Seconda Università degli Studi di Napoli, Naples, Italy.
Francesco
F
Testa
Settimio
S
Rossi
Andrea
A
Sodi
Ilaria
I
Passerini
Valentina
V
Di Iorio
Michele
M
Della Corte
Sandro
S
Banfi
Enrico Maria
EM
Surace
Ugo
U
Menchini
Alberto
A
Auricchio
Francesca
F
Simonelli
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005451:Fluorescein Angiography; D015316:Genetic Therapy; D006801:Humans; D008268:Macular Degeneration / Q000151:congenital / Q000235:genetics / Q000503:physiopathology*; D008875:Middle Aged; D012160:Retina / Q000503:physiopathology*; D055211:Retinal Photoreceptor Cell Inner Segment / Q000473:pathology*; D055214:Retinal Photoreceptor Cell Outer Segment / Q000473:pathology*; D000080362:Stargardt Disease; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology*; D058609:Visual Field Tests; D014794:Visual Fields / Q000502:physiology; D055815:Young Adult
C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters