To explore the anatomic correlation of the retinal cone mosaic on adaptive optics images.
Retrospective nonconsecutive observational case series.
A retrospective review of the multimodal imaging charts of 6 patients with focal alteration of the cone mosaic on adaptive optics was performed. Retinal diseases included acute posterior multifocal placoid pigment epitheliopathy (n = 1), hydroxychloroquine retinopathy (n = 1), and macular telangiectasia type 2 (n = 4). High-resolution retinal images were obtained using a flood-illumination adaptive optics camera. Images were recorded using standard imaging modalities: color and red-free fundus camera photography; infrared reflectance scanning laser ophthalmoscopy, fluorescein angiography, indocyanine green angiography, and spectral-domain optical coherence tomography (OCT) images.
On OCT, in the marginal zone of the lesions, a disappearance of the interdigitation zone was observed, while the ellipsoid zone was preserved. Image recording demonstrated that such attenuation of the interdigitation zone co-localized with the disappearance of the cone mosaic on adaptive optics images. In 1 case, the restoration of the interdigitation zone paralleled that of the cone mosaic after a 2-month follow-up.
Our results suggest that the interdigitation zone could contribute substantially to the reflectance of the cone photoreceptor mosaic. The absence of cones on adaptive optics images does not necessarily mean photoreceptor cell death.
Adaptive optics is a new imaging modality allowing visualization of the cone mosaic. However, the subcellular structure of cone photoreceptors at the origin of their reflectance on adaptive optics images remains uncertain. The aim of this study was to improve our understanding of the origin of the hyperreflective signal leading to the cone mosaic pattern on adaptive optics images. For this purpose, we retrospectively analyzed the multimodal imaging data of 6 cases of 3 different diseases affecting the outer retina.
Patients and Methods
The charts of 6 patients who had been examined between October 2013 and January 2014 were retrospectively reviewed. One patient had acute posterior multifocal placoid pigment epitheliopathy (APMPPE), 1 patient had hydroxychloroquine retinopathy, and 4 patients had macular telangiectasia type 2. All patients underwent multimodal imaging in addition to the routine examination.
This institutional clinical study was registered on clinicaltrials.gov (NCT01546181) and the procedures conformed to the tenets of the Declaration of Helsinki. Approval of the Ethics Committee of Saint-Antoine Hospital (Paris, France) was obtained.
All patients underwent a comprehensive ophthalmologic examination, including the measurement of the best-corrected visual acuity (BCVA); dilated funduscopic examination; color and red-free fundus camera photography; infrared reflectance scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) imaging (Spectralis OCT; Heidelberg Engineering, Heidelberg, Germany). Fluorescein angiography (FA) and indocyanine green angiography (ICGA) were performed when necessary at the treating clinician’s discretion. In addition, adaptive optics images were obtained using a commercially available flood-illumination adaptive optics camera (rtx 1; Imagine Eyes, France). Retinal images were obtained in a 20 degree horizontal and 12 degree vertical field. Adaptive optics images were assembled in a montage and overlaid on the fundus photographs and the fundus projection of OCT images using i2k (DualAlign LLC, Clifton Park, New York, USA), GIMP v2.8.10, www.gimp.org, and Powerpoint (Microsoft, Seattle, Washington, USA).
A 35-year-old man with bilateral blurred vision, redness, and photophobia for 7 days and a history of viral syndrome 2 weeks prior was diagnosed with bilateral APMPPE. Baseline BCVA was 20/20.
Multimodal imaging of the paracentral lesion in the right eye showed a yellowish-white lesion on color photographs, early hypofluorescence and late staining on FA, hypo-autofluorescence on fundus autofluorescence, and hypofluorescence at the early and late phase of ICGA. On OCT, the outer retina was severely affected at the lesion center. Both the ellipsoid and the interdigitation zones had disappeared. Adaptive optics imaging showed a central zone of coarse, hyperreflective spots. On the edge of the lesion, the ellipsoid zone was slightly attenuated, while the interdigitation zone was absent. This surrounding zone co-localized with a circular dark annulus devoid of cone mosaic on adaptive optics images. A normal cone mosaic was observed outside of the lesion.
After a 2-month follow-up, the lesion appeared smaller and, on adaptive optics images, its center was atrophic and contained highly hyperreflective structures. The latter co-localized with hyperreflective deposits in or on the retinal pigment epithelium (RPE) layer on OCT. The edge of the lesion (ie, the previously dark annulus) showed a normal cone mosaic structure on adaptive optics images, with restoration of the interdigitation zone on OCT ( Figure 1 ).
A 45-year-old woman with a history of hydroxychloroquine sulfate intake for 20 years, at a dose of 200 mg/d for 10 years and then 400 mg/d for the next 10 years, was referred for retinopathy screening. The BCVA was 20/20. The treatment was discontinued because of paracentral defects on the Humphrey visual field test.
Multimodal imaging showed a central hyperreflective area on the infrared image (IR) surrounded by a hyporeflective annular structure in both eyes. Fundus autofluorescence was normal. OCT showed normal outer retinal layers in the central zone, whereas in the surrounding zone corresponding to the hyporeflective annular structure on IR a strong attenuation of the interdigitation zone was clearly seen. The overlying ellipsoid layer was still present and only slightly attenuated.
The central foveal zone showed the preservation of the outer retinal layers. This phenomenon of foveal photoreceptor resistance to toxic effects has been previously described.
Adaptive optics images of the central zone of the retina revealed a normal cone mosaic structure up to approximately 2 degrees from the center, which corresponded to a zone of normal outer retinal layers on OCT. An annular structure surrounding this central zone was detected at the limit between the normal and atrophic retina. On adaptive optics, the disappearance of the normal cone mosaic was progressively replaced by a blurred image with black and gray spots. This zone corresponded to the highly attenuated interdigitation zone on OCT, although the ellipsoid zone was still present ( Figure 2 ).
Patients 3, 4, 5, and 6
Four patients diagnosed with early-stage macular telangiectasia type 2 (MacTel2) were seen for annual follow-up as part of the MacTel natural history study. The visual acuity ranged from 20/50 to 20/25. Red-free fundus camera photography showed a whitening of the temporal side of the macular area. Fundus autofluorescence showed a slightly increased fluorescence temporal to the fovea. OCT showed foveal and parafoveal cysts in the inner and outer retina with disruption of the interdigitation and ellipsoid zones and a normal retinal thickness. Figure 3 shows the left eye of 1 patient with a visual acuity at 20/25. Nasal to the fovea, a zone with disappearance of the interdigitation zone but intact ellipsoid zone was seen. Adaptive optics images showed the disappearance of the cone mosaic in this area.