Interocular Symmetry of Foveal Cone Topography in Congenital Achromatopsia

Litts, Katie M.; Georgiou, Michalis; Langlo, Christopher S; Patterson, Emily J; Mastey, Rebecca; Kalitzeos, Angelos; Linderman, Rachel E; Lam, Byron L.; Fishman, Gerald A.; Pennesi, Mark E.; Kay, Christine N.; Hauswirth, William W.; Michaelides, Michel; Carroll, Joseph

doi:10.1080/02713683.2020.1737138

Cited by 26 publications

(20 citation statements)

References 39 publications

(61 reference statements)

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“…15,18,20,26,28,40 Moreover, interocular symmetry extends to the topography of the foveal cone mosaic as imaged with adaptive optics scanning light ophthalmoscopy. 16,41 Given the structural and functional symmetry, it can be assumed that both eyes in patients with ACHM have similar therapeutic potential.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Investigation of Retinal Function in Patients with Achromatopsia

Georgiou

Singh

Kane

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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To investigate the long-term natural history of retinal function of achromatopsia (ACHM). METHODS. Subjects with molecularly confirmed ACHM were recruited in a prospective cohort study of mesopic microperimetry. Coefficient of repeatability and intraclass correlation coefficient (ICC) of mean sensitivity (MS) were calculated. Best-corrected visual acuity (BCVA), bivariate contour ellipse area (BCEA), contrast sensitivity (CS), MS, total volume (V TOT), and central field volume (V 5°) from volumetric and topographic analyses were acquired. Correlation of functional parameters with structural findings from optical coherence tomography (OCT) was performed. RESULTS. Eighteen subjects were recruited. Mean follow-up was 7.2 years. The MS testretest repeatability coefficient was 1.65 decibels (dB), and the ICC was 0.973 (95% confidence interval, 0.837-0.98). Mean MS was similar for right and left eyes (16.97dB and 17.14dB, respectively). A negative significant correlation between logMAR BCVA and the retinal sensitivity indices (MS, V TOT , V 5°) was found. A significant negative correlation between logCS and MS, V TOT , and V 5°w as also observed. BCVA and BCEA improved during follow-up. Mean CS, MS, V TOT , and V 5°a t final follow-up were similar to baseline. MS was similar between CNGA3-and CNGB3-ACHM. Patients with and without the presence of a foveal ellipsoid zone on OCT had similar MS (16.64 dB and 17.17 dB, respectively). CONCLUSIONS. We demonstrate a highly reproducible assessment of MS. Retinal function including MS, volumetric indices, and CS are stable in ACHM. Improvement of fixation stability and small changes of BCVA over time may be part of the natural history of the disease.

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Section: Discussionmentioning

confidence: 99%

Long-Term Investigation of Retinal Function in Patients with Achromatopsia

Georgiou

Singh

Kane

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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“…Axial length was measured using a Zeiss IOL Master (Carl Zeiss Meditec, Jena, Germany) and used to scale AOSLO images as previously described. 26 AOSLO montages were manually aligned using Adobe Photoshop CS6 to infrared reflectance and en face SDOCT images using retinal vasculature. For intrapatient comparisons between visits, AOSLO montages were transformed to the same scale (µm/pixel).…”

Section: Methodsmentioning

confidence: 99%

Longitudinal Assessment of Remnant Foveal Cone Structure in a Case Series of Early Macular Telangiectasia Type 2

Litts

Okada

Heeren

et al. 2020

Trans. Vis. Sci. Tech.

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Purpose To determine the extent of remnant cone structure within early foveal ellipsoid zone (EZ) lesions in macular telangiectasia type 2 longitudinally using both confocal and split detector adaptive optics scanning light ophthalmoscopy (AOSLO). Methods Spectral domain optical coherence tomography (SDOCT), confocal and split detector AOSLO were acquired from seven patients (10 eyes) with small (early) EZ lesions on SDOCT secondary to macular telangiectasia type 2 at baseline, 6 months, and 12 months. The presence of cone structure on AOSLO in areas of EZ loss as well as cones at 1° eccentricity, and their change over time were quantified. Results By split detector AOSLO, remnant cone structure was identified within and on the borders of all foveal EZ lesions. Within the extent of these lesions, cone spacing ranged from 4.97 to 9.95 µm at baseline, 5.30 to 6.10 µm at 6 months, and 4.99 to 7.12 µm at 12 months. Four eyes with significantly smaller EZ lesions showed evidence of recovery of EZ reflectivity on SDOCT B-scans. Remnant cone structure was identified in some areas where EZ reflectivity recovered at the following time point. Eyes that showed recovery of EZ reflectivity had a continuous external limiting membrane. Conclusions Remnant cone structure can persist within small SDOCT-defined EZ lesions, which can wax and wane in appearance over time. AOSLO can help to inform the interpretation of SDOCT imaging. Translational Relevance The absence of EZ in early macular telangiectasia type 2 and other retinal conditions needs careful interpretation because it does not always indicate an absence of underlying cone structure. The integrity of the external limiting membrane may better predict the presence of remnant cone structure and recovery of EZ reflectivity.

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“…[21][22][23][24] Marked variability in the cone mosaic has been observed across patients with ACHM. 23,[25][26][27][28] Nonconfocal split-detection AOSLO demonstrated that inner segment structure remained in these "dark spaces." The degree of remnant inner segment structure may be important for participant selection for gene therapy trials and could be used to identify patients most likely to benefit from cone-directed rescue.…”

Section: Introductionmentioning

confidence: 99%

Intraobserver Repeatability and Interobserver Reproducibility of Foveal Cone Density Measurements in CNGA3- and CNGB3-Associated Achromatopsia

Georgiou

Litts

Singh

et al. 2020

Trans. Vis. Sci. Tech.

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To examine repeatability and reproducibility of foveal cone density measurements in patients with CNGA3-and CNGB3-associated achromatopsia (ACHM) using split-detection adaptive optics scanning light ophthalmoscopy (AOSLO). Methods: Thirty foveae from molecularly confirmed subjects with ACHM, half of whom harbored disease-causing variants in CNGA3 and half in CNGB3, underwent nonconfocal split-detection AOSLO imaging. Cone photoreceptors within the manually delineated rod-free zone were manually identified twice by two independent observers. The coordinates of the marked cones were used for quantifying foveal cone density. Cone density and difference maps were generated to compare cone topography between trials. Results: We observed excellent intraobserver repeatability in foveal cone density estimates, with intraclass correlation coefficients (ICCs) ranging from 0.963 to 0.991 for CNGA3 and CNGB3 subjects. Interobserver reproducibility was also excellent for both CNGA3 (ICC = 0.952; 95% confidence interval [CI], 0.903-1.0) and CNGB3 (ICC = 0.968; 95% CI, 0.935-1.0). However, Bland-Altman analysis revealed bias between observers. Conclusions: Foveal cone density can be measured using the described method with good repeatability and reproducibility both for CNGA3-and CNGB3-associated ACHM. Any degree of bias observed among the observers is of uncertain clinical significance but should be evaluated on a study-specific basis. Translational Relevance: This approach could be used to explore disease natural history, as well as to facilitate stratification of patients and monitor efficacy of interventions for ongoing and upcoming ACHM gene therapy trials.

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Interocular Symmetry of Foveal Cone Topography in Congenital Achromatopsia

Cited by 26 publications

References 39 publications

Long-Term Investigation of Retinal Function in Patients with Achromatopsia

Long-Term Investigation of Retinal Function in Patients with Achromatopsia

Longitudinal Assessment of Remnant Foveal Cone Structure in a Case Series of Early Macular Telangiectasia Type 2

Intraobserver Repeatability and Interobserver Reproducibility of Foveal Cone Density Measurements in CNGA3- and CNGB3-Associated Achromatopsia

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