Ultra-Wide–Field and Autofluorescence Imaging of Choroidal Dystrophies

Introduction

Choroideremia and gyrate atrophy are generalized choroidal dystrophies. Choroideremia is an X-linked recessive disorder localized to Xq13-q22, whereas gyrate is autosomal recessive localized to 10q26. The two diseases have overlapping features including diffuse peripheral loss of the retinal pigment epithelium and choriocapillaris and late involvement of the posterior pole. The first area affected is usually the midperiphery and imaging of these cases by traditional angiography has limitations.¹ In advanced cases, these conditions can be difficult to distinguish.

Traditional fluorescein angiography typically captures 30° or 50° of the fundus in one image. Imaging protocols have been developed to view the periphery; for example, the Early Treatment of Diabetic Retinopathy Study 7-field protocol visualizes 75°.² Photomontages can be assembled to obtain a wide-field image.³ However, manual or automated photomontages, including multi-field imaging systems, have inherent difficulties such as matching intensity and contrast levels, peripheral field of view aberrations, defocusing of the periphery, and misalignment of images. Fluorescein angiography montages are also unable to image the entire retina at single time points and the quality of the peripheral views is also dependent on the skills of the photographer. These limitations make assembling photomontages a laborious, imprecise, and inconsistent process.

A recent ultra-wide–field imaging technique allows 200° of the retina to be captured in a single image (essentially the entire retina). This ultra-wide angle field is achieved by using a confocal scanning laser ophthalmoscope with dual focal points, one of which lies posterior to the iris plane. This yields increased depth of focus and improved imaging through media opacities such as cataract and inflammation. Despite the curved nature of the retina, all points in the image are focused using this imaging modality.⁴

We present 5 cases of choroidal dystrophy in which ultra-wide–field imaging was undertaken. These cases highlight the characteristic features of these conditions as visualized by ultra-wide–field imaging.

Report

Institutional Review Board approval was obtained for a retrospective review of the Jules Stein Eye Institute imaging database. Two characteristic cases of gyrate atrophy, 3 cases of choroideremia, and 1 choroideremia carrier were reviewed. Their clinical characteristics are given in the table. Cases 1 and 2 are siblings. Cases 3 and 4 are also siblings and case 6 is their mother. Wide-field images were taken with the Optos ultra-wide–field imaging system (Optomap fa; Optos plc, Dunfermline, UK). Traditional fundus images were taken with a Zeiss FF 450 fundus camera (Carl Zeiss Meditec, Dublin, CA) and autofluorescence images were taken with a Heidelberg Spectralis imaging system (Heidelberg Engineering, Vista, CA).

Table: Patient Clinical Details

Gyrate atrophy cases demonstrated severe and confluent chorioretinal atrophy that extended from just anterior to the posterior pole to the periphery. This area of involvement was symmetric and sharply demarcated 360° posteriorly and typically failed to involve the posterior pole or the ora serrata region (Fig. 1), although patches of chorioretinal atrophy were identified more posteriorly in advanced cases (Fig. 2). The distinct margins of these atrophic lesions give it a characteristic “scalloped” appearance (Fig. 1). These features of gyrate atrophy were difficult to appreciate with conventional 50° fundus photography (Fig. 1A) because the lesions often do not involve the posterior pole. Montage composites were necessary to identify the characteristic lesions of gyrate atrophy using conventional fundus photography (Fig. 1B), whereas a single image using the ultra-wide–field imaging system nicely highlighted the salient features (Fig. 1C). On wide-field fluorescein angiography (Fig. 1D), the borders between the atrophic areas and normal choroid and retina exhibited leakage and staining from the sclera underneath. Baring of the large choroidal vessels was also evident in the areas of choriocapillaris loss (Fig. 1D).

Figure 1. Comparison of Traditional Fundus Photography (50°) and Ultra-Wide–Field Scanning Laser Ophthalmoscopy in a Patient with Gyrate Atrophy. (A) Traditional Fundus Photograph (50°). (B) Montage Color Photograph. (C) Ultra-Wide–Field Color Photograph. (D) Ultra-Wide–Field Fluorescein Angiogram. Note the Well-Delineated and Scalloped Posterior Edge, Which Hyperfluoresced Late Due to Local Diffusion of Dye and Staining of the Sclera. Posterior Pole Involvement in Gyrate Atrophy Is Typically Patchy, as Seen Here. A Montage Was Necessary to Visualize All of the Salient Features Using Traditional Photography, Whereas a Single Image Was Sufficient Using Ultra-Wide–Field Imaging.

Figure 2. Comparison of a Montage and Ultra-Wide–Field Imaging in a Patient with Advanced Gyrate Atrophy and Cataract. (A) Montage Color Photograph. (B) Ultra-Wide–Field Color Photograph. (C) Ultra-Wide–Field Fluorescein Angiogram. The Distinct Posterior Borders Were Better Appreciated in the Ultra-Wide–Field Images. Note the Better Image Quality of the Ultra-Wide–Field Images in This Patient Who Had a Cataract.

Media opacities such as cataracts degrade the image quality of traditional fundus photographs more than ultra-wide–field images. Due to a cataract in one of our patients, adequate peripheral views were not obtainable to reconstruct a comprehensive montage (Fig. 2A). However, sufficient detail of the periphery is discernable with ultra-wide–field photography and fluorescein angiography (Figs. 2B and 2C). The distinct, scalloped posterior borders of the gyrate lesions are much more evident in the ultra-wide–field images compared with the montage. In advanced cases of gyrate atrophy, ultra-wide–field imaging can help facilitate and document the proper diagnosis, especially with media opacities.

In contrast to gyrate atrophy, choroideremia cases demonstrated more patchy, irregular, and asymmetric chorioretinal degeneration in the periphery that involved the posterior pole but spared the central macular region. The borders of the atrophic lesions in choroideremia were much less distinct when compared with gyrate atrophy and the lesions exhibited a more diffuse loss of pigment (Fig. 3). Advanced cases of choroideremia exhibited coalescing atrophic lesions extending from the posterior pole to the periphery (Fig. 4) and can be confused with gyrate atrophy lesions (Figs. 1 and 2). Mid-phase fluorescein angiography demonstrated baring of the large choroidal vessels due to severe chorioretinal degeneration and choriocapillaris loss in the areas of atrophy (Fig. 4B). Late phase angiograms demonstrated staining in areas of atrophy (Fig 3B). Autofluorescence imaging of two patients with choroideremia revealed coalescing hypo-autofluorescent patches with hyper-autofluorescent halos that represent a signature diagnostic finding (Fig. 5). These hypo-autofluorescent patches were in the posterior pole, but spared the central macula. The pattern observed with autofluorescence imaging was distinct from the pattern observed with color photography and fluorescein angiography.

Figure 3. Ultra-Wide–Field Imaging of Siblings with Choroideremia. (A) Color Photograph of Patient 3. (B) Late Phase Fluorescein Angiogram of Patient 3. (C) Color Photograph of Patient 4, a Sibling of Patient 3. Macular Pigmentation Causing the Dark Central Area and Hypo-Fluoresence, Respectively, Can Be Present in Choroideremia. Note also the Less Distinct Posterior Edge Compared to Gyrate Atrophy.

Figure 4. Ultra-Wide–Field Imaging of a Patient with Advanced Choroideremia. (A) Color Photograph. (B) Magnified Mid-Phase Fluorescein Angiogram. Note Sparing of the Macula and Central Macular Region. Advanced Cases of Choroideremia Can Be Confused with Gyrate Atrophy.

Figure 5. Autofluorescence Imaging of Siblings with Choroideremia. (A) Patient 3. (B) Patient 4. Large Coalescing Patches of Hypo-Autofluorescence with Distinct Borders Were Observed in the Posterior Pole. Compared with Figures 3A and 3C, These Patches Were Undetectable on Wide-Field Imaging.

Our carrier case demonstrated grade 2 peripheral reticular degeneration⁵ with a normal posterior pole and no evidence of chorioretinal atrophy (Fig. 6).

Figure 6. Ultra-Wide–Field Imaging of a Carrier of Choroideremia. (A) Color Photograph. (B) Fluorescein Angiogram. Peripheral Reticular Degeneration of the Retinal Pigment Epithelium Is Observed in Both the Color Photograph and Fluorescein Angiogram.

Discussion

Gyrate atrophy and choroideremia are diffuse choroidal degenerative diseases that are associated with panretinal degeneration in the absence of typical signs of retinitis pigmentosa such as bone spicule migration and optic nerve atrophy. The wide-field imaging system allows a much greater area of the fundus to be viewed, creating a panoramic view that better delineates the overall pattern of choroidal degeneration. The figures with traditional angiography (Figs. 1A, 1B, and 2A) and ultra-wide–field imaging (Figs. 1C, 1D, 2B, 3, and 4) demonstrate that choroidal degeneration is better appreciated with wide-field imaging.

This study demonstrates for the first time wide-field color photographic and fluorescein angiographic imaging of the periphery of these two diseases. Several features of this imaging system are highlighted. Color images are reconstructed from red and green wavelength lasers. With the absence of a blue laser, the color perception is different from light-based imaging.

There are several advantages to ultra-wide–field imaging. It has the theoretical advantage of being less affected by media opacities such as cataract (Fig. 2). Ultra-wide–field fluorescein angiography also allows for the entire fundus to be imaged at single time points (Figs. 1D, 2C, 3B, 4B, and 6B), which is not possible with montage composites of traditional fluorescein angiograms. Additionally, montage reconstructions require careful planning and photographer skill at imaging the far periphery. Finally, patients with photophobia often tolerate wide-field angiography better because the light is less intense.

Disadvantages to ultra-wide–field imaging include artifacts such as imaging of the eyelashes and the nose. There is also some distortion in the far periphery and a loss of resolution when the image is magnified. Finally, the absence of a blue laser generates images with inaccurate color reproduction and red saturation.

Our case series is limited by the small number of patients presenting with choroidal dystrophies. A larger case series would help further demonstrate the benefits of wide-field imaging compared with traditional fundus imaging. A second limitation to our study is the absence of photomontages or multi-field images covering the entire periphery 360° for comparison. However, our inability to obtain these other modalities for comparison in these rare disorders further highlights their disadvantages. Photomontages must be carefully planned and retrospective assembly of montages is often difficult or unobtainable.

Choroideremia and gyrate atrophy are rare conditions with phenotypes that can be confused. Fluorescein angiography can aid in diagnosis and ultra-wide–field angiography allows visualization of this pathology to be more precise.