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Leber congenital amaurosis caused by Lebercilin (LCA5) mutation: retained photoreceptors adjacent to retinal disorganization.

Jacobson SG, Aleman TS, Cideciyan AV, Sumaroka A, Schwartz SB, Windsor EA, Swider M, Herrera W, Stone EM - Mol. Vis. (2009)

Bottom Line: P1 showed a prominent central island of retinal pigment epithelium (RPE) surrounded by alternating elliptical-appearing areas of decreased and increased pigmentation.Retinal remodeling was present in pericentral regions in both patients.The NIR reflectance and NIR-AF imaging in the younger patient suggested preserved RPE in retinal regions with retained photoreceptors.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA. jacobsos@mail.med.upenn.edu

ABSTRACT

Purpose: To determine the retinal disease expression in the rare form of Leber congenital amaurosis (LCA) caused by Lebercilin (LCA5) mutation.

Methods: Two young unrelated LCA patients, ages six years (P1) and 25 years (P2) at last visit, both with the same homozygous mutation in the LCA5 gene, were evaluated clinically and with noninvasive studies. En face imaging was performed with near-infrared (NIR) reflectance and autofluorescence (AF); cross-sectional retinal images were obtained with optical coherence tomography (OCT). Dark-adapted thresholds were measured in the older patient; and the transient pupillary light reflex was recorded and quantified in both patients.

Results: Both LCA5 patients had light perception vision only, hyperopia, and nystagmus. P1 showed a prominent central island of retinal pigment epithelium (RPE) surrounded by alternating elliptical-appearing areas of decreased and increased pigmentation. Retinal laminar architecture at and near the fovea was abnormal in both patients. Foveal outer nuclear layer (ONL) was present in P1 and P2 but to different degrees. With increasing eccentricity, there was retinal laminar disorganization. Regions of pericentral and midperipheral retina in P1, but not P2, could retain measurable ONL and less laminopathy. P2 had a small central island of perception with >5 log units of sensitivity loss. Pupillary responsiveness was present in both LCA5 patients; the thresholds were abnormally elevated by >or=5.5 log units.

Conclusions: LCA5 patients had evidence of retained photoreceptors mainly in the central retina. Retinal remodeling was present in pericentral regions in both patients. The NIR reflectance and NIR-AF imaging in the younger patient suggested preserved RPE in retinal regions with retained photoreceptors. Detailed phenotype studies in other LCA5 patients with longitudinal follow-up will help determine the feasibility of future intervention in this rare disease.

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En face near-infrared reflectance and autofluorescence images of the LCA5 patients. A: Near-infrared (NIR) reflectance (REF) image of the left fundus of P1 is shown. Inset to the left is a schematic drawing of the retinal regions corresponding to low reflection (black), intermediate reflection (hatched), and high reflection and choroidal visibility (white). Inset to the right is a NIR reflectance view of the fundus of a 6 year-old child with normal vision. B: Near-infrared-autofluorescence (NIR-AF) image of the left fundus of P1 is shown. Black arrows indicate the boundaries of the midperipheral transitions to healthier retinal pigment epithelium; and gray arrow points to the parafoveal annular region of low intensity. Inset is a normal image. C: NIR reflectance image of the left fundus of P2 is shown. Inset is an enlarged view of the optic nerve head (ONH) region with ONH drusen. D: NIR-AF image of the left fundus of P2 is shown. Inset is an enlarged view of the ONH region. All images are shown contrast stretched for visibility of features.
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f1: En face near-infrared reflectance and autofluorescence images of the LCA5 patients. A: Near-infrared (NIR) reflectance (REF) image of the left fundus of P1 is shown. Inset to the left is a schematic drawing of the retinal regions corresponding to low reflection (black), intermediate reflection (hatched), and high reflection and choroidal visibility (white). Inset to the right is a NIR reflectance view of the fundus of a 6 year-old child with normal vision. B: Near-infrared-autofluorescence (NIR-AF) image of the left fundus of P1 is shown. Black arrows indicate the boundaries of the midperipheral transitions to healthier retinal pigment epithelium; and gray arrow points to the parafoveal annular region of low intensity. Inset is a normal image. C: NIR reflectance image of the left fundus of P2 is shown. Inset is an enlarged view of the optic nerve head (ONH) region with ONH drusen. D: NIR-AF image of the left fundus of P2 is shown. Inset is an enlarged view of the ONH region. All images are shown contrast stretched for visibility of features.

Mentions: P1, at age 6 years, had light perception vision, hyperopia (+6.50 sphere), nystagmus, and no corneal or lenticular opacities. An en face montage of the ocular fundus of P1 using NIR reflectance imaging showed a distinctly demarcated dark central island surrounded by alternating elliptical regions of lighter and darker appearance (Figure 1A). A schematic of the darker-appearing regions is shown (Figure 1A, inset left). The reflectance pattern in LCA5 P1 was in contrast to the more homogeneous NIR reflectance view from an age-matched normal subject (Figure 1A, inset right). The lighter regions in LCA5 P1 showed greater visibility of the choroid, suggesting depigmentation of RPE. Darker regions likely correspond to more preserved RPE. NIR-AF provided further information on the RPE with the use of melanosome-specific signals from the fundus [31]. High intensity NIR-AF signal originates from the irregular-shaped central island, suggesting a preserved or hyperpigmented RPE at this location (Figure 1B). There was a region of lower intensity NIR-AF in the parafovea, and this likely corresponds to chorioretinal atrophic change. At greater eccentricities, there was an incremental increase in NIR-AF. In the superotemporal and superonasal near midperiphery, there was a distinct boundary of a further increase in NIR-AF signal with a spatially homogeneous appearance, representing more retained and pigmented RPE.


Leber congenital amaurosis caused by Lebercilin (LCA5) mutation: retained photoreceptors adjacent to retinal disorganization.

Jacobson SG, Aleman TS, Cideciyan AV, Sumaroka A, Schwartz SB, Windsor EA, Swider M, Herrera W, Stone EM - Mol. Vis. (2009)

En face near-infrared reflectance and autofluorescence images of the LCA5 patients. A: Near-infrared (NIR) reflectance (REF) image of the left fundus of P1 is shown. Inset to the left is a schematic drawing of the retinal regions corresponding to low reflection (black), intermediate reflection (hatched), and high reflection and choroidal visibility (white). Inset to the right is a NIR reflectance view of the fundus of a 6 year-old child with normal vision. B: Near-infrared-autofluorescence (NIR-AF) image of the left fundus of P1 is shown. Black arrows indicate the boundaries of the midperipheral transitions to healthier retinal pigment epithelium; and gray arrow points to the parafoveal annular region of low intensity. Inset is a normal image. C: NIR reflectance image of the left fundus of P2 is shown. Inset is an enlarged view of the optic nerve head (ONH) region with ONH drusen. D: NIR-AF image of the left fundus of P2 is shown. Inset is an enlarged view of the ONH region. All images are shown contrast stretched for visibility of features.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2690955&req=5

f1: En face near-infrared reflectance and autofluorescence images of the LCA5 patients. A: Near-infrared (NIR) reflectance (REF) image of the left fundus of P1 is shown. Inset to the left is a schematic drawing of the retinal regions corresponding to low reflection (black), intermediate reflection (hatched), and high reflection and choroidal visibility (white). Inset to the right is a NIR reflectance view of the fundus of a 6 year-old child with normal vision. B: Near-infrared-autofluorescence (NIR-AF) image of the left fundus of P1 is shown. Black arrows indicate the boundaries of the midperipheral transitions to healthier retinal pigment epithelium; and gray arrow points to the parafoveal annular region of low intensity. Inset is a normal image. C: NIR reflectance image of the left fundus of P2 is shown. Inset is an enlarged view of the optic nerve head (ONH) region with ONH drusen. D: NIR-AF image of the left fundus of P2 is shown. Inset is an enlarged view of the ONH region. All images are shown contrast stretched for visibility of features.
Mentions: P1, at age 6 years, had light perception vision, hyperopia (+6.50 sphere), nystagmus, and no corneal or lenticular opacities. An en face montage of the ocular fundus of P1 using NIR reflectance imaging showed a distinctly demarcated dark central island surrounded by alternating elliptical regions of lighter and darker appearance (Figure 1A). A schematic of the darker-appearing regions is shown (Figure 1A, inset left). The reflectance pattern in LCA5 P1 was in contrast to the more homogeneous NIR reflectance view from an age-matched normal subject (Figure 1A, inset right). The lighter regions in LCA5 P1 showed greater visibility of the choroid, suggesting depigmentation of RPE. Darker regions likely correspond to more preserved RPE. NIR-AF provided further information on the RPE with the use of melanosome-specific signals from the fundus [31]. High intensity NIR-AF signal originates from the irregular-shaped central island, suggesting a preserved or hyperpigmented RPE at this location (Figure 1B). There was a region of lower intensity NIR-AF in the parafovea, and this likely corresponds to chorioretinal atrophic change. At greater eccentricities, there was an incremental increase in NIR-AF. In the superotemporal and superonasal near midperiphery, there was a distinct boundary of a further increase in NIR-AF signal with a spatially homogeneous appearance, representing more retained and pigmented RPE.

Bottom Line: P1 showed a prominent central island of retinal pigment epithelium (RPE) surrounded by alternating elliptical-appearing areas of decreased and increased pigmentation.Retinal remodeling was present in pericentral regions in both patients.The NIR reflectance and NIR-AF imaging in the younger patient suggested preserved RPE in retinal regions with retained photoreceptors.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA. jacobsos@mail.med.upenn.edu

ABSTRACT

Purpose: To determine the retinal disease expression in the rare form of Leber congenital amaurosis (LCA) caused by Lebercilin (LCA5) mutation.

Methods: Two young unrelated LCA patients, ages six years (P1) and 25 years (P2) at last visit, both with the same homozygous mutation in the LCA5 gene, were evaluated clinically and with noninvasive studies. En face imaging was performed with near-infrared (NIR) reflectance and autofluorescence (AF); cross-sectional retinal images were obtained with optical coherence tomography (OCT). Dark-adapted thresholds were measured in the older patient; and the transient pupillary light reflex was recorded and quantified in both patients.

Results: Both LCA5 patients had light perception vision only, hyperopia, and nystagmus. P1 showed a prominent central island of retinal pigment epithelium (RPE) surrounded by alternating elliptical-appearing areas of decreased and increased pigmentation. Retinal laminar architecture at and near the fovea was abnormal in both patients. Foveal outer nuclear layer (ONL) was present in P1 and P2 but to different degrees. With increasing eccentricity, there was retinal laminar disorganization. Regions of pericentral and midperipheral retina in P1, but not P2, could retain measurable ONL and less laminopathy. P2 had a small central island of perception with >5 log units of sensitivity loss. Pupillary responsiveness was present in both LCA5 patients; the thresholds were abnormally elevated by >or=5.5 log units.

Conclusions: LCA5 patients had evidence of retained photoreceptors mainly in the central retina. Retinal remodeling was present in pericentral regions in both patients. The NIR reflectance and NIR-AF imaging in the younger patient suggested preserved RPE in retinal regions with retained photoreceptors. Detailed phenotype studies in other LCA5 patients with longitudinal follow-up will help determine the feasibility of future intervention in this rare disease.

Show MeSH
Related in: MedlinePlus