Photoreceptor Structure and Function in Patients with Congenital Achromatopsia

Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, USA.
Investigative ophthalmology & visual science (Impact Factor: 3.4). 07/2011; 52(10):7298-308. DOI: 10.1167/iovs.11-7762
Source: PubMed


To assess photoreceptor structure and function in patients with congenital achromatopsia.
Twelve patients were enrolled. All patients underwent a complete ocular examination, spectral-domain optical coherence tomography (SD-OCT), full-field electroretinographic (ERG), and color vision testing. Macular microperimetry (MP; in four patients) and adaptive optics (AO) imaging (in nine patients) were also performed. Blood was drawn for screening of disease-causing genetic mutations.
Mean (± SD) age was 30.8 (± 16.6) years. Mean best-corrected visual acuity was 0.85 (± 0.14) logarithm of the minimal angle of resolution (logMAR) units. Seven patients (58.3%) showed either an absent foveal reflex or nonspecific retinal pigment epithelium mottling to mild hypopigmentary changes on fundus examination. Two patients showed an atrophic-appearing macular lesion. On anomaloscopy, only 5 patients matched over the entire range from 0 to 73. SD-OCT examination showed a disruption or loss of the macular inner/outer segments (IS/OS) junction of the photoreceptors in 10 patients (83.3%). Seven of these patients showed an optically empty space at the level of the photoreceptors in the fovea. AO images of the photoreceptor mosaic were highly variable but significantly disrupted from normal. On ERG testing, 10 patients (83.3%) showed evidence of residual cone responses to a single-flash stimulus response. The macular MP testing showed that the overall mean retinal sensitivity was significantly lower than normal (12.0 vs. 16.9 dB, P < 0.0001).
The current approach of using high-resolution techniques to assess photoreceptor structure and function in patients with achromatopsia should be useful in guiding selection of patients for future therapeutic trials as well as monitoring therapeutic response in these trials.

26 Reads
  • Source
    • "If so, correct intracellular M-opsin distribution should also be restored since cone cell bodies are still be present although cone functional degeneration has occurred early. This would have important implications for human Cnga3 achromatopsia which is characterized by a gradual and variable degree of cone loss [9], [40]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Achromatopsia is a rare autosomal recessive disorder which shows color blindness, severely impaired visual acuity, and extreme sensitivity to bright light. Mutations in the alpha subunits of the cone cyclic nucleotide-gated channels (CNGA3) are responsible for about 1/4 of achromatopsia in the U.S. and Europe. Here, we test whether gene replacement therapy using an AAV5 vector could restore cone-mediated function and arrest cone degeneration in the cpfl5 mouse, a naturally occurring mouse model of achromatopsia with a CNGA3 mutation. We show that gene therapy leads to significant rescue of cone-mediated ERGs, normal visual acuities and contrast sensitivities. Normal expression and outer segment localization of both M- and S-opsins were maintained in treated retinas. The therapeutic effect of treatment lasted for at least 5 months post-injection. This study is the first demonstration of substantial, relatively long-term restoration of cone-mediated light responsiveness and visual behavior in a naturally occurring mouse model of CNGA3 achromatopsia. The results provide the foundation for development of an AAV5-based gene therapy trial for human CNGA3 achromatopsia.
    PLoS ONE 04/2012; 7(4):e35250. DOI:10.1371/journal.pone.0035250 · 3.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Die räumliche Orientierung und das Beurteilen von Distanzen sind ebenso wie die Farbwahrnehmung im visuellen System verankert. Allerdings sind verschiedene Zentren – ausgehend vom primären visuellen Kortex im Okzipitallappen – in unterschiedlicher Ausprägung in die verschiedenen Aspekte der visuellen Verarbeitung involviert. In diesem Artikel werden Untersuchungstechniken und -designs beschrieben, welche mittels funktioneller Magnetresonanztomographie (fMRT) die verschiedenen Aufgaben innerhalb des visuellen Systems den jeweils dafür spezialisierten Zentren im Parietal- bzw. Temporallappen zuordnen können.
    Der Radiologe 07/2013; 53(7). DOI:10.1007/s00117-013-2482-9 · 0.43 Impact Factor
  • Source
    Topics in Adaptive Optics, 01/2012; , ISBN: 978-953-307-949-3
Show more