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Research Letters |

High-Definition Optical Coherence Tomographic Visualization of Photoreceptor Layer and Retinal Flecks in Fundus Albipunctatus Associated With Cone Dystrophy FREE

Giuseppe Querques, MD; Pascal Carrillo, MD; Lea Querques, MD; Anna V. Bux, MD; Maria V. Del Curatolo, MD; Nicola Delle Noci, MD
Arch Ophthalmol. 2009;127(5):703-706. doi:10.1001/archophthalmol.2009.87.
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Fundus albipunctatus was originally thought to be a stationary disease. Lauber1 first described fundus albipunctatus and differentiated it from retinitis punctata albescens (a progressive tapetoretinal degeneration). Several investigators, however, recently suggested that cone dystrophy gradually develops in some patients.24 It was reported that mutations of the 11-cis–retinol dehydrogenase (RDH5) gene, which is expressed predominantly in the retinal pigment epithelium (RPE), cause fundus albipunctatus.5

In this article, we show by high-definition optical coherence tomography (OCT) in vivo the disruption of the photoreceptor (PR) layer and hyperreflective lesions located in the inner part of the RPE in a patient with fundus albipunctatus associated with cone dystrophy.

A 47-year-old woman was referred to our department for gradual progression of visual impairment, including constriction of the visual field, night blindness, and photophobia. The patient, who had initially noticed poor night vision during childhood, was clinically diagnosed with fundus albipunctatus a few years earlier by a local ophthalmologist; this diagnosis was then confirmed by direct genomic sequencing, showing a homozygous Gly35Ser mutation of the RDH5 gene. The patient signed a comprehensive consent form according to good clinical practice guidelines before proceeding with any examinations. Best-corrected visual acuity was 20/80 OU. Fundus examination revealed numerous yellow-white flecks throughout the midperipheral to far-peripheral retina, and the maculae each showed a bull’s-eye lesion (Figure 1). Fundus autofluorescence showed an abnormal circular hypoautofluorescence within the macular area surrounded by a hyperautofluorescent halo in both eyes (Figure 1). The standard flash electroretinogram disclosed severely decreased a- and b-waves in both eyes after 30 minutes of dark adaptation. After 2 hours of dark adaptation, standard flash electroretinogram a- and b-waves showed recovery, although not to the normal level. The photopic electroretinogram and multifocal electroretinogram responses were significantly reduced. High-definition spectral-domain OCT (OCT 4000 Cirrus; Humphrey-Zeiss, San Leandro, California) showed reduction of central macular thickness in both eyes and allowed for visualization of transverse PR loss in the foveal region as well as disruption and focal loss of the inner segment–outer segment junction (Figure 2). Moreover, in correspondence with retinal flecks, we observed hyperreflective lesions seen as dome-shaped deposits located in the inner part of the RPE layer and at the level of the outer segment of the PR continuous with the RPE layer (Figure 2).

Place holder to copy figure label and caption
Figure 1.

Color fundus photographs of the right (A) and left (B) eyes show numerous yellow-white flecks throughout the midperipheral retina and a bull’s-eye lesion at the macula. Fundus autofluorescence in the right (C) and left (D) eyes shows an abnormal circular hypofluorescence within the macular area surrounded by a hyperautofluorescent halo in both eyes.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

High-definition spectral-domain optical coherence tomographic scans in the right (A) and left (B) eyes allow for visualization of transverse photoreceptor loss in the foveal region as well as disruption and focal loss of the inner segment (IS)–outer segment (OS) junction. In correspondence with retinal flecks, high-definition spectral-domain optical coherence tomographic scans in the right (C) and left (D) eyes show hyperreflective lesions (arrowheads in enlarged view) seen as dome-shaped deposits located in the inner part of the retinal pigment epithelium (RPE) layer and at the level of the OS of the photoreceptor continuous with the RPE layer.

Graphic Jump Location

High-definition OCT is a high-speed OCT system using spectral- or Fourier-domain detection with an axial image resolution of 5 μm. Hence, in vivo visualization of intraretinal structures and especially the RPE as well as the inner segment and outer segment of the PR layer is possible. In our patient, high-definition OCT allowed not only visualization of transverse PR loss in the foveal region but also, in correspondence with retinal flecks, hyperreflective lesions located in the inner part of the RPE, similar to type 1 lesions reported for Stargardt disease.6 Moreover, these high-definition OCT hyperreflective lesions due to a deficiency of 11-cis–retinol dehydrogenase look similar to the retinal deposits reported by Berson7 in squirrels that are deprived of vitamin A by dietary restriction.

To our knowledge, there is no histopathologic study of eyes with fundus albipunctatus and no previous description of the layer within the retina in which the flecks in this disease occur.

In conclusion, we show in vivo the disruption of the PR layer in fundus albipunctatus (a disease caused by a gene [RDH5] expressed in the RPE) associated with cone dystrophy as well as hyperreflective lesions similar to those reported for Stargardt disease (a disease caused by a gene [ABCA4] expressed in the PR). This may be the first solid evidence indicating the location of the flecks in fundus albipunctatus.

Correspondence: Dr G. Querques, Policlinico Riuniti di Foggia, University of Foggia, Viale Pinto, 1, 71100 Foggia, Italy (giuseppe.querques@hotmail.it).

Author Contributions: Dr G. Querques had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Financial Disclosure: None reported.

Lauber  H Die sogenaunte retinitis punctata albescens. Klin Monatsbl Augenheilkd 1910;48133- 148
Nakamura  MHotta  YTanikawa  ATerasaki  HMiyake  Y A high association with cone dystrophy in fundus albipunctatus caused by mutations of the RDH5 gene. Invest Ophthalmol Vis Sci 2000;41 (12) 3925- 3932
PubMed
Miyake  YShiroyama  NSugita  SHoriguchi  MYagasaki  K Fundus albipunctatus associated with cone dystrophy. Br J Ophthalmol 1992;76 (6) 375- 379
PubMed Link to Article
Wada  YAbe  TSato  HTamai  M A novel Gly35Ser mutation in the RDH5 gene in a Japanese family with fundus albipunctatus associated with cone dystrophy. Arch Ophthalmol 2001;119 (7) 1059- 1063
PubMed Link to Article
Yamamoto  HSimon  AEriksson  UHarris  EBerson  ELDryja  TP Mutations in the gene encoding 11-cis retinol dehydrogenase cause delayed dark adaptation and fundus albipunctatus. Nat Genet 1999;22 (2) 188- 191
PubMed Link to Article
Querques  GLeveziel  NBenhamou  NVoigt  MSoubrane  GSouied  EH Analysis of retinal flecks in fundus flavimaculatus using optical coherence tomography. Br J Ophthalmol 2006;90 (9) 1157- 1162
PubMed Link to Article
Berson  EL Experimental and therapeutic aspects of photic damage to the retina. Invest Ophthalmol Vis Sci 1973;1235- 44

Figures

Place holder to copy figure label and caption
Figure 1.

Color fundus photographs of the right (A) and left (B) eyes show numerous yellow-white flecks throughout the midperipheral retina and a bull’s-eye lesion at the macula. Fundus autofluorescence in the right (C) and left (D) eyes shows an abnormal circular hypofluorescence within the macular area surrounded by a hyperautofluorescent halo in both eyes.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

High-definition spectral-domain optical coherence tomographic scans in the right (A) and left (B) eyes allow for visualization of transverse photoreceptor loss in the foveal region as well as disruption and focal loss of the inner segment (IS)–outer segment (OS) junction. In correspondence with retinal flecks, high-definition spectral-domain optical coherence tomographic scans in the right (C) and left (D) eyes show hyperreflective lesions (arrowheads in enlarged view) seen as dome-shaped deposits located in the inner part of the retinal pigment epithelium (RPE) layer and at the level of the OS of the photoreceptor continuous with the RPE layer.

Graphic Jump Location

Tables

References

Lauber  H Die sogenaunte retinitis punctata albescens. Klin Monatsbl Augenheilkd 1910;48133- 148
Nakamura  MHotta  YTanikawa  ATerasaki  HMiyake  Y A high association with cone dystrophy in fundus albipunctatus caused by mutations of the RDH5 gene. Invest Ophthalmol Vis Sci 2000;41 (12) 3925- 3932
PubMed
Miyake  YShiroyama  NSugita  SHoriguchi  MYagasaki  K Fundus albipunctatus associated with cone dystrophy. Br J Ophthalmol 1992;76 (6) 375- 379
PubMed Link to Article
Wada  YAbe  TSato  HTamai  M A novel Gly35Ser mutation in the RDH5 gene in a Japanese family with fundus albipunctatus associated with cone dystrophy. Arch Ophthalmol 2001;119 (7) 1059- 1063
PubMed Link to Article
Yamamoto  HSimon  AEriksson  UHarris  EBerson  ELDryja  TP Mutations in the gene encoding 11-cis retinol dehydrogenase cause delayed dark adaptation and fundus albipunctatus. Nat Genet 1999;22 (2) 188- 191
PubMed Link to Article
Querques  GLeveziel  NBenhamou  NVoigt  MSoubrane  GSouied  EH Analysis of retinal flecks in fundus flavimaculatus using optical coherence tomography. Br J Ophthalmol 2006;90 (9) 1157- 1162
PubMed Link to Article
Berson  EL Experimental and therapeutic aspects of photic damage to the retina. Invest Ophthalmol Vis Sci 1973;1235- 44

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