Spectral-Domain Optical Coherence Tomography Staging and Autofluorescence Imaging in Achromatopsia

Abstract

IMPORTANCE Evidence is mounting that achromatopsia is a progressive retinal degeneration, and treatments for this condition are on the horizon.OBJECTIVES To categorize achromatopsia into clinically identifiable stages using spectral-domain optical coherence tomography and to describe fundus autofluorescence imaging in this condition. DESIGN, SETTING, AND PARTICIPANTSA prospective observational study was performed between 2010 and 2012 at the Edward S. Harkness Eye Institute, New York-Presbyterian Hospital. Participants included 17 patients (aged 10-62 years) with full-field electroretinography-confirmed achromatopsia.MAIN OUTCOMES AND MEASURES Spectral-domain optical coherence tomography features and staging system, fundus autofluorescence and near-infrared reflectance features and their correlation to optical coherence tomography, and genetic mutations served as the outcomes and measures. RESULTS Achromatopsia was categorized into 5 stages on spectral-domain optical coherence tomography: stage 1 (2 patients [12%]), intact outer retina; stage 2 (2 patients [12%]), inner segment ellipsoid line disruption; stage 3 (5 patients [29%]), presence of an optically empty space; stage 4 (5 patients [29%]), optically empty space with partial retinal pigment epithelium disruption; and stage 5 (3 patients [18%]), complete retinal pigment epithelium disruption and/or loss of the outer nuclear layer. Stage 1 patients showed isolated hyperreflectivity of the external limiting membrane in the fovea, and the external limiting membrane was hyperreflective above each optically empty space. On near infrared reflectance imaging, the fovea was normal, hyporeflective, or showed both hyporeflective and hyperreflective features. All patients demonstrated autofluorescence abnormalities in the fovea and/or parafovea: 9 participants (53%) had reduced or absent autofluorescence surrounded by increased autofluorescence, 4 individuals (24%) showed only reduced or absent autofluorescence, 3 patients (18%) displayed only increased autofluorescence, and 1 individual (6%) exhibited decreased macular pigment contrast. Inner segment ellipsoid line loss generally correlated with the area of reduced autofluorescence, but hyperautofluorescence extended into this region in 2 patients (12%). Bilateral coloboma-like atrophic macular lesions were observed in 1 patient (6%). Five novel mutations were identified (4 in the CNGA3 gene and 1 in the CNGB3 gene).CONCLUSIONS AND RELEVANCE Achromatopsia often demonstrates hyperautofluorescence suggestive of progressive retinal degeneration. The proposed staging system facilitates classification of the disease into different phases of progression and may have therapeutic implications.

A Prospective Longitudinal Study of Retinal Structure and Function in Achromatopsia

“…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.…”

Achromatopsia: On the Doorstep of a Possible Therapy

“…Several clinical studies in recent years have investigated outer retinal architecture and foveal morphology in detail using high-resolution optical coherence tomography (OCT) and adaptive optics [12,13,14,27,29,30,31,32,33,34]. The macular appearance in OCT can show either normal lamination or variable degrees of disruption of the photoreceptor layers and loss of retinal pigment epithelium.…”

“…In recent years, several studies have investigated photoreceptor morphology in ACHM [29,30,31,32,33,34]. Carroll et al [32] observed a severely disrupted cone mosaic in the fovea and parafoveal area of a single patient with mutations in CNGB3.…”

“…ACHM has long been considered an ideal target for gene therapy based on the observation that - in contrast to other progressive retinal dystrophies - functioning photoreceptors are expected to be largely preserved [27,28,29,30,31,32,33,34]. A further advantage is that small- (mouse) and large- (dog and sheep) animal models exist for all three major genetic forms (CNGA3, CNGB3, and GNAT2) of the disease in which this hypothesis could be tested [15,16,17,18,19].…”

Significance of the hyperautofluorescent ring associated with choroidal neovascularisation in eyes undergoing anti-VEGF therapy for wet age-related macular degeneration

“…Twenty per cent (20.9%) of the eyes in their series had a hyper-type or mixed-type FAF, and this finding was significantly associated with loss of the ellipsoid zone line of the photoreceptors on OCT, suggesting that a larger hyper-FAF-type or mixed-FAF-type lesion may indicate a more severely damaged ellipsoid zone line 22. On the other hand, Greenberg et al 25 evaluated the autofluorescence features of achromatopsia and concluded that the area of HAF found in 71% of their patients likely reflected increased cone outer segment turnover, marked by intensified bisretinoid deposition in the RPE.…”