Diagnostic Fundus Autofluorescence Patterns in Achromatopsia

Fahim, Abigail T.; Khan, Naheed W.; Zahid, Sarwar; Schachar, Ira H.; Branham, Kari; Kohl, Susanne; Wissinger, Bernd; Elner, Victor M.; Heckenlively, John R.; Jayasundera, Thiran

doi:10.1016/j.ajo.2013.06.033

Cited by 39 publications

(46 citation statements)

References 33 publications

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“…Our findings of three distinct FAF patterns is in broad agreement with those of Fahim et al 24 We also found a very small but statistically significant increase in the area of reduced FAF over time among patients who displayed that pattern, indicating that serial FAF may play a role in assessing change in ACHM. There was no statistically significant difference between ages in the three FAF patterns.…”

Section: Fundus Autofluorescencesupporting

confidence: 93%

“…This factor, along with the significant degree of patient variability observed, also highlights the need to consider patients on an individual basis in terms of potential suitability for intervention. The use of further quantitative FAF analyses 24,35,36 may increase the sensitivity of FAF assessment in ACHM, but it is still likely that any progression by this measure will occur at a very slow rate in a subset of patients.…”

Section: Fundus Autofluorescencementioning

confidence: 97%

“…Michaelides et al 23 reported that the FAF appearance was normal in five affected members of a GNAT2 family. In a recent study of 10 achromats, Fahim et al 24 suggested an age-dependent change in FAF, with younger patients exhibiting increased foveal autofluorescence (AF), whereas older patients had reduced AF with discrete borders corresponding to outer retinal defects on SD-OCT. Greenberg et al 25 also observed FAF abnormalities, including increased and/or decreased AF (n ¼ 17). However, again these were cross-sectional studies of relatively small size, with no longitudinal FAF data in ACHM published to date.…”

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confidence: 98%

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A Prospective Longitudinal Study of Retinal Structure and Function in Achromatopsia

Aboshiha

Dubis

Cowing

et al. 2014

Invest. Ophthalmol. Vis. Sci.

110

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Previously published cross-sectional studies have described conflicting findings with respect to the age-dependency of progression. This study, which constitutes the largest and longest prospective longitudinal study of ACHM to date, suggests that although ACHM may be progressive, any such progression is slow and subtle in most patients, and does not correlate with age or genotype. We also describe the first serial assessment of FAF, which is highly variable between individuals, even of similar age and genotype.

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Section: Fundus Autofluorescencesupporting

confidence: 93%

Section: Fundus Autofluorescencementioning

confidence: 97%

mentioning

confidence: 98%

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A Prospective Longitudinal Study of Retinal Structure and Function in Achromatopsia

Aboshiha

Dubis

Cowing

et al. 2014

Invest. Ophthalmol. Vis. Sci.

110

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“…However, ERG recordings demonstrate that their cone function is attenuated, but not absent 19,41 . This is in contrast to ERG recordings in most human ACHM patients in which cone function is usually undetectable [51][52][53][54] to be further investigated.…”

Section: Discussioncontrasting

confidence: 55%

Gene Augmentation Therapy Restores Retinal Function and Visual Behavior in a Sheep Model of CNGA3 Achromatopsia

et al. 2015

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Achromatopsia is a hereditary form of day blindness caused by cone photoreceptor dysfunction. Affected patients suffer from congenital color blindness, photosensitivity, and low visual acuity. Mutations in the CNGA3 gene are a major cause of achromatopsia, and a sheep model of this disease was recently characterized by our group. Here, we report that unilateral subretinal delivery of an adeno-associated virus serotype 5 (AAV5) vector carrying either the mouse or the human intact CNGA3 gene under the control of the red/green opsin promoter results in long-term recovery of visual function in CNGA3-mutant sheep. Treated animals demonstrated shorter maze passage times and a reduced number of collisions with obstacles compared with their pretreatment status, with values close to those of unaffected sheep. This effect was abolished when the treated eye was patched. Electroretinography (ERG) showed marked improvement in cone function. Retinal expression of the transfected human and mouse CNGA3 genes at the mRNA level was shown by polymerase chain reaction (PCR), and cone-specific expression of CNGA3 protein was demonstrated by immunohistochemisrty. The rescue effect has so far been maintained for over 3 years in the first-treated animals, with no obvious ocular or systemic side effects. The results support future application of subretinal AAV5-mediated gene-augmentation therapy in CNGA3 achromatopsia patients.

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“…In a recently published study, most of the CNGA3 mutated patients had nonrecordable photopic and 30 Hz flicker responses. Photopic ERG responses of CNGB3 patients were more variable and ranged from nonrecordable to barely detectable responses [25]. Fahim et al suggest that this difference demonstrates that the beta subunit loss is better tolerated than the alpha subunit loss [25].…”

Section: Discussionmentioning

confidence: 99%

Flicker cone function in normal and day blind sheep: a large animal model for human achromatopsia caused by CNGA3 mutation

et al. 2014

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Purpose Recently we reported on day blindness in sheep caused by a mutation in the CNGA3 gene, thus making affected sheep a naturally occurring large animal model for therapeutic intervention in CNGA3 achromatopsia patients. The purpose of this study was to characterize flicker cone function in normal and day blind sheep, with the aim of generating a normative data base for ongoing gene therapy studies. Methods Electoretinographic (ERG) cone responses were evoked with full-field conditions in 10 normal, 6 heterozygous carriers and 36 day blind sheep. Following light adaptation (10 min, 30 cd/m2), responses were recorded at four increasing light intensities (1, 2.5, 5 and 10 cd s/m2). At each of these intensities, a single photopic flash response followed by 8 cone flicker responses (10–80 Hz) was recorded. Results were used to generate a normative data base for the three groups. Differences between day blind and normal control animals were tested in two age-matched groups (n = 10 per group). Results The normal sheep cone ERG wave is bipartite in nature, with critical flicker fusion frequency (CFF) >80 Hz. In all four flash intensities, the single photopic flash a-wave and b-wave amplitudes were significantly lower (p < 0.005), and implicit times significantly delayed (p < 0.0001), in day blind animals. In all four flash intensities, CFF values were significantly lower (p < 0.0001) in day blind sheep. Conclusions Cone function is severely depressed in day blind sheep. Our results will provide a normative data base for ongoing gene therapy studies.

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Diagnostic Fundus Autofluorescence Patterns in Achromatopsia

Cited by 39 publications

References 33 publications

A Prospective Longitudinal Study of Retinal Structure and Function in Achromatopsia

A Prospective Longitudinal Study of Retinal Structure and Function in Achromatopsia

Gene Augmentation Therapy Restores Retinal Function and Visual Behavior in a Sheep Model of CNGA3 Achromatopsia

Flicker cone function in normal and day blind sheep: a large animal model for human achromatopsia caused by CNGA3 mutation

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