Adaptive Optics Imaging of Foveal Sparing in Geographic Atrophy Secondary to Age-Related Macular Degeneration

Querques, Giuseppe; Kamami-Levy, Cynthia; Georges, Anouk; Pedinielli, Alexandre; Capuano, Vittorio; Blanco-Garavito, Rocío; Poulon, Fanny; Souied, Eric H.

doi:10.1097/iae.0000000000000692

Cited by 24 publications

(13 citation statements)

References 29 publications

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“…This may be because the preserved foveal region was too small to evoke normal ERGs, and we suggest that the etiology of our three cases was similar to that reported by Kondo et al 44 A sparing of the fovea is commonly observed in different types of macular diseases, such as in ABCA4-and PRPH2associated retinopathies, 17,18,43,[45][46][47][48] mitochondrial retinal dystrophy, 49 macular dystrophy with CRB1 mutation, 50 and agerelated macular degeneration. [51][52][53][54] The explanations for the physiologic and anatomic sparing of the fovea have been presented in many publications. [55][56][57][58][59][60][61][62][63] However, foveal sparing in these macular diseases is usually accompanied by RPE atrophy around the fovea, and the border between the atrophic region and normal fovea is distinct.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the pathologic mechanism for the foveal sparing may differ between the cases with POC1B mutations and other macular dystrophies. 17,18,43,[45][46][47][48][49][50][51][52][53][54] Although the numbers of the eyes with foveal sparing are limited, further investigations to determine whether there is a significant association between the genotype and RPE findings (i.e., the presence or absence of RPE atrophy) in a large cohort with foveal sparing could determine the mechanism of the foveal sparing.…”

Section: Discussionmentioning

confidence: 99%

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Phenotypical Characteristics ofPOC1B-Associated Retinopathy in Japanese Cohort: Cone Dystrophy With Normal Funduscopic Appearance

Kameya

Fujinami

Ueno

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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Citation: Kameya S, Fujinami K, Ueno S, et al. Phenotypical characteristics of POC1B-associated retinopathy in Japanese cohort: cone dystrophy with normal funduscopic appearance. Invest Ophthalmol Vis Sci. 2019;60:3432-3446. https://doi.org/ 10.1167/iovs.19-26650 PURPOSE. Cone/cone-rod dystrophy is a large group of retinal disorders with both phonotypic and genetic heterogeneity. The purpose of this study was to characterize the phenotype of eight patients from seven families harboring POC1B mutations in a cohort of the Japan Eye Genetics Consortium (JEGC). METHODS.Whole-exome sequencing with targeted analyses identified homozygous or compound heterozygous mutations of the POC1B gene in 7 of 548 families in the JEGC database. Ophthalmologic examinations including the best-corrected visual acuity, perimetry, fundus photography, fundus autofluorescence imaging, optical coherence tomography, and full-field and multifocal electroretinography (ERGs) were performed.RESULTS. There were four men and four women whose median age at the onset of symptoms was 15.6 years (range, 6-23 years) and that at the time of examination was 40.3 years (range, 22-67 years). The best-corrected visual acuity ranged from À0.08 to 1.52 logMAR units. The funduscopic appearance was normal in all the cases except in one case with faint mottling in the fovea. Optical coherence tomography revealed an absence of the interdigitation zone and blurred ellipsoid zone in the posterior pole, but the foveal structures were preserved in three cases. The full-field photopic ERGs were reduced or extinguished with normal scotopic responses. The central responses of the multifocal ERGs were preserved in two cases. The diagnosis was either generalized cone dystrophy in five cases or cone dystrophy with foveal sparing in three cases.CONCLUSIONS. Generalized or peripheral cone dystrophy with normal funduscopic appearance is the representative phenotype of POC1B-associated retinopathy in our cohort.Whole-exome sequencing and targeted sequence analyses of the 301 retinal disease-associated genes (including genes of Retnet; https://sph.uth.edu/retnet/, in the public domain) were done according to the published protocol of the NISO. 35 Paired-end sequence library construction and exome capturing Downloaded from iovs.arvojournals.org on 07/08/2020 FIGURE 8. Horizontal and vertical OCT images of the left eye of patient 1 recorded at the age 35 years (A) and 39 years (B).Longitudinal reflectivity profiles at the fovea are shown below the OCT images. EZ and IZ are preserved in the fovea at the age 35 years but they are blurred at the age of 39 years. The reflectivity profiles show small peaks of IZ at the age 35 years but not at 39 years. The reflectance intensity of the IZ relative to the RPE was 0.82 at the age 35 years and 0.63 at the age 39 years. The reflectance intensity of the EZ relative to the RPE was 0.86 at the age 35 years and 0.77 at the age 39 years. The reflectivity was averaged in width as indicated by the yellow lines. ILM, internal limiting membra...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Phenotypical Characteristics ofPOC1B-Associated Retinopathy in Japanese Cohort: Cone Dystrophy With Normal Funduscopic Appearance

Kameya

Fujinami

Ueno

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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“…Cells are variably identified among these authors, including RPE 48 , RPE packed with pigment granules 4, 6, 54, 55 , RPE/macrophages 38 , and melanin-containing cells. 59 Like others using electron microscopy, we considered these subretinal cells RPE, because they contained numerous RPE-characteristic granules at a concentration resembling that of cells in the RPE layer 8, 18 and because evidence for other cell types was lacking.…”

Section: Discussionmentioning

confidence: 99%

Visualizing Retinal Pigment Epithelium Phenotypes in the Transition to Geographic Atrophy in Age-Related Macular Degeneration

Zanzottera

Ach

Huisingh

et al. 2016

Retina

136

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Purpose To inform the interpretation of clinical optical coherence tomography and fundus autofluorescence?imaging in geographic atrophy (GA) of age-related macular degeneration (AMD) by determining the distribution of retinal pigment epithelium (RPE) phenotypes in the transition from health to atrophy (GA) in donor eyes. Method In RPE-Bruch’s membrane flat mounts of 2 GA eyes the terminations of organized RPE cytoskeleton and autofluorescent material were compared. In high-resolution histological sections of 13 GA eyes, RPE phenotypes were assessed at ±500 and ±100 µm from the descent of the external limiting membrane (ELM) towards Bruch’s membrane. The ELM descent was defined as curved, reflected, or oblique in shape. Thicknesses of RPE, basal laminar deposit (BLamD), and RPE+BLamD were measured. Results A border of atrophy that can be precisely delimited is the ELM descent, as opposed to the termination of the RPE layer itself, because of dissociated RPE in the atrophic area. Approaching the ELM descent, the percentage of abnormal RPE morphologies increases, the percentage of age-normal cells decreases, overall RPE thickens, and BLamD does not thin. The combination of RPE plus BLamD is 19.7% thicker at −100 µm from the ELM descent than at −500 µm (23.1 ± 10.7 vs 19.3 ± 8.2 µm; p=0.05). Conclusion The distribution of RPE phenotypes at the GA transition support the idea that these morphologies represent defined stages of a degeneration sequence. The idea RPE dysmorphia including rounding and stacking helps explain variable autofluorescence patterns in GA 14 is reinforced. The ELM descent and RPE+BLamD thickness profile may have utility as SDOCT metrics in clinical trials.

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“…32,37 Such pattern of early relative preservation of visual acuity and then rapid loss is reminiscent of numerous maculopathies that show preservation of visual acuity despite severe central retinal disease. [79][80][81][82][83][84] Thus, visual acuity in this condition, as in most IRDs, is not a reliable indicator of the severity of the central retinal phenotype, although it is critical to the patients' quality of life. 27,78 Once the central island is compromised a rapid decline of the patients' VA may be expected.…”

Section: Discussionmentioning

confidence: 99%

RDH12Mutations Cause a Severe Retinal Degeneration With Relatively Spared Rod Function

Alemán

Uyhazi

Serrano

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To describe the retinal phenotype of pediatric patients with mutations in the retinol dehydrogenase 12 (RDH12) gene. METHODS. Twenty-one patients from 14 families (ages 2-17 years) with RDH12-associated inherited retinal degeneration (RDH12-IRD) underwent a complete ophthalmic exam and imaging with spectral domain optical coherence tomography (SD-OCT) and near infrared and short-wavelength fundus autofluorescence. Visual field extent was measured with Goldmann kinetic perimetry, visual thresholds with dark-adapted static perimetry or with dark-adapted chromatic full-field stimulus testing (FST) and transient pupillometry. RESULTS. Visual acuity ranged from 20/40 to light perception. There was parafoveal depigmentation or atrophic maculopathies accompanied by midperipheral intraretinal pigment migration. SD-OCT revealed foveal thinning in all patients and detectable but thinned outer nuclear layer (ONL) at greater eccentricities from the fovea. Photoreceptor outer segment (POS) signals were only detectable in small pockets within the central retina. Measurable kinetic visual fields were limited to small (<5-108) central islands of vision. Electroretinograms were reported as undetectable or severely reduced in amplitude. FST sensitivities to a 467 nm stimulus were rod-mediated and reduced on average by~2.5 log units. A thinned central ONL colocalized with severely reduced to nondetectable conemediated sensitivities. Pupillometry confirmed the psychophysically measured abnormalities. CONCLUSIONS. RDH12-IRD causes an early-onset, retina-wide disease with particularly severe central retinal abnormalities associated with relatively less severe rod photoreceptor dysfunction, a pattern consistent with an early-onset cone-rod dystrophy. Severely abnormal POS but detectable ONL in the pericentral and peripapillary retina suggest these regions may become targets for gene therapy.

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Adaptive Optics Imaging of Foveal Sparing in Geographic Atrophy Secondary to Age-Related Macular Degeneration

Cited by 24 publications

References 29 publications

Phenotypical Characteristics ofPOC1B-Associated Retinopathy in Japanese Cohort: Cone Dystrophy With Normal Funduscopic Appearance

Phenotypical Characteristics ofPOC1B-Associated Retinopathy in Japanese Cohort: Cone Dystrophy With Normal Funduscopic Appearance

Visualizing Retinal Pigment Epithelium Phenotypes in the Transition to Geographic Atrophy in Age-Related Macular Degeneration

RDH12Mutations Cause a Severe Retinal Degeneration With Relatively Spared Rod Function

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