Multimodal imaging including semiquantitative short-wavelength and near-infrared autofluorescence in achromatopsia

Invest. Ophthalmol. Vis. Sci.

Singh

Kane

et al. 2020

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.

Section: Discussionmentioning

confidence: 91%

Long-Term Investigation of Retinal Function in Patients with Achromatopsia

Invest. Ophthalmol. Vis. Sci.

Singh

Kane

et al. 2020

“…However, the clinical significance of FAF in ACHM remains poorly established, and we would predict that any progression in this parameter is likely to be slow and small in magnitude. Interestingly, recent work by Matet et al 15 has advocated the role of near-infrared autofluorescence (NIR-AF) in the investigation of ACHM. While the Spectralis device performs short-wavelength autofluorescence (SW-AF) imaging, NIR-AF is a less frequently used imaging modality.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Assessment of Retinal Structure in Achromatopsia Patients With Long-Term Follow-up

Hirji

Invest. Ophthalmol. Vis. Sci.

Kalitzeos

et al. 2018

PurposeTo longitudinally characterize structural retinal changes in achromatopsia (ACHM) over extended follow-up.MethodsFifty molecularly confirmed ACHM subjects underwent serial spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) imaging. Foveal structure on SD-OCT was graded and compared for evidence of progression, and foveal total retinal thickness (FTRT) and outer nuclear layer (ONL) thickness were serially measured. FAF patterns were characterized and compared over time.ResultsMean SD-OCT follow-up was 61.6 months (age range at baseline, 6–52 years). Forty-five of the subjects had serial FAF (mean follow-up: 48.5 months). Only 6 (12%) of the subjects demonstrated qualitative change on serial foveal SD-OCT scans. Among the entire cohort, there was no statistically significant change over time in FTRT (P = 0.2459) or hyporeflective zone (HRZ) diameter (P = 0.3737). There was a small—but statistically significant—increase in ONL thickness (P = 0.0084). Three different FAF patterns were observed: centrally increased FAF (13/45), normal FAF (14/45), and well-demarcated reduced FAF (18/45), with the latter group displaying a small gradual increase in the area of reduced FAF of 0.055 mm2 over 43.4 months (P = 0.0011).ConclusionsThis longitudinal study of retinal structure in ACHM represents the largest cohort and longest follow-up period to date. Our findings support the presiding notion that ACHM is essentially a stationary condition regarding retinal structure, and any change over time is likely to be small, slow, and variable across patients. This may potentially afford a wider window for therapeutic intervention.

“…For example, Sundaram et al 12 and Langlo et al 8 reported symmetry in the grade of the ellipsoid zone disruption on OCT (using this fact to support a study design in which they conducted more detailed analyses in just one eye of each subject). In addition, Matet et al 31 found no interocular difference in the size of ellipsoid zone defect on OCT. Mastey et al 11 also demonstrated no significant difference in foveal ONL thickness in 76 subjects with ACHM (though the ONL thickness was generally reduced compared to control subjects). In addition, Matet et al 31 showed no difference between eyes in the extent of the hyperautofluorescent perifoveal ring observed using short-wavelength autofluorescence or the extent of the central hypoautofluorescence observed using near-infrared autofluorescence.…”

Section: Accepted Manuscriptmentioning

confidence: 95%

“…In addition, Matet et al 31 found no interocular difference in the size of ellipsoid zone defect on OCT. Mastey et al 11 also demonstrated no significant difference in foveal ONL thickness in 76 subjects with ACHM (though the ONL thickness was generally reduced compared to control subjects). In addition, Matet et al 31 showed no difference between eyes in the extent of the hyperautofluorescent perifoveal ring observed using short-wavelength autofluorescence or the extent of the central hypoautofluorescence observed using near-infrared autofluorescence. Aboshiha et al 17 also reported no difference in fundus autofluorescence between eyes in a cohort of 38 patients with ACHM.…”

Section: Accepted Manuscriptmentioning

confidence: 95%

Interocular Symmetry of Foveal Cone Topography in Congenital Achromatopsia

Litts

Langlo

et al. 2020

Current Eye Research

Purpose: To determine interocular symmetry of foveal cone topography in achromatopsia (ACHM) using non-confocal split-detection adaptive optics scanning light ophthalmoscopy (AOSLO).Methods: Split-detector AOSLO images of the foveal cone mosaic were acquired from both eyes of 26 subjects (mean age 24.3 years; range 8 -44 years, 14 females) with genetically confirmed CNGA3-or CNGB3-associated ACHM. Cones were identified within a manually delineated rod-free zone. Peak cone density (PCD) was determined using an 80 × 80 μm sampling window within the rod-free zone. The mean and standard deviation (SD) of intercell distance (ICD) were calculated to derive the coefficient of variation (CV). Cone density difference maps were generated to compare cone topography between eyes.Results: PCD (mean ± SD) was 17,530 ± 9,614 cones/mm 2 and 17,638 ± 9,753 cones/mm 2 for right and left eyes, respectively (p = 0.677, Wilcoxon test). The mean (± SD) for ICD was 9.05 ± 2.55 µm and 9.24 ± 2.55 µm for right and left eyes, respectively (p = 0.410, paired t test). The mean (± SD) for CV of ICD was 0.16 ± 0.03 µm and 0.16 ± 0.04 µm for right and left eyes, respectively (p = 0.562, paired t test). Cone density maps demonstrated that cone topography of the ACHM fovea is non-uniform with local variations in cone density between eyes.Conclusions: These results demonstrate interocular symmetry of the foveal cone mosaic (both density and packing) in ACHM. As cone topography can differ between eyes of a subject, PCD does not completely describe the foveal cone mosaic in ACHM. Nonetheless, these findings are of value in longitudinal monitoring of patients during treatment trials and further suggest that both eyes of a given subject may have similar therapeutic potential and non-study eye can be used as a control.