Long-Term Investigation of Retinal Function in Patients with Achromatopsia

Abstract

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.

Clinical and Molecular Characterization of Achromatopsia Patients: A Longitudinal Study

“…Our findings are in agreement with the observations of Sundram et al who reported a decline of MS with age in 40 patients [23]. Conversely, Aboshiha et al and more recently Georgiou et al did not observe significant changes in MS in 38 and 18 patients, respectively [9,24]. These discrepancies may be due to the shorter follow-up reported in the first case (i.e., 19.5 months) [9] and to the different distribution of mutated genes [24].…”

“…As regards the retinal function, we found that MS negatively correlated with patient's age and decreased significantly over the follow-up period. To date, only few studies assessed the MS of ACHM patients by MP [9,23,24,32]. Our findings are in agreement with the observations of Sundram et al who reported a decline of MS with age in 40 patients [23].…”

“…Conversely, Aboshiha et al and more recently Georgiou et al did not observe significant changes in MS in 38 and 18 patients, respectively [9,24]. These discrepancies may be due to the shorter follow-up reported in the first case (i.e., 19.5 months) [9] and to the different distribution of mutated genes [24]. Finally, we observed unrecordable or markedly reduced light-adapted responses that did not change significantly during the follow-up.…”

“…Defining the disease course can have important implications for therapies, hence the need to conduct longitudinal studies. Although several studies [4,5,9,[22][23][24][25] looked into the clinical course of ACHM patients to assess disease progression, there is still an open debate on whether ACHM is a progressive or stable condition. In particular, some reports showed that at least a subset of patients present progressive vision loss with impaired cone photoreceptor function and poorly preserved foveal integrity [4,5,9,26,27].…”

Disease Progression in CNGA3 and CNGB3 Retinopathy; Characteristics of Slovenian Cohort and Proposed OCT Staging Based on Pooled Data from 126 Patients from 7 Studies

“…Several studies explored the clinical course of ACHM patients to assess disease progression [18,19,22,[25][26][27][28]. Although some reports showed visual and structural deterioration [18,19,22,28,29], other studies report no correlation of clinical presentation with age [12,17,25].…”