Outer retinal structure in patients with acute zonal occult outer retinopathy

Abstract

Purpose: To correlate visual function with high-resolution images of retinal structure using adaptive optics scanning laser ophthalmoscopy (AOSLO) in 4 patients with acute zonal occult outer retinopathy (AZOOR).

Design: Observational case series.

Methods: Four women, aged 18 to 51, with acute focal loss of visual field or visual acuity, photopsia, and minimal funduscopic changes were studied with best-corrected visual acuity (BCVA), Goldmann kinetic and automated perimetry and fundus-guided microperimetry, full-field and multifocal electroretinography (ffERG and mfERG), spectral-domain optical coherence tomography (SD-OCT), and AOSLO imaging. Cone spacing was measured in 4 eyes and compared with 27 age-similar normal eyes. Additional functional testing in 1 patient suggested that cones were absent but rods remained. Serum from all patients was analyzed for anti-retinal antibody activity.

Results: In all patients vision loss was initially progressive, then stable. Symptoms were unilateral in 2 and bilateral but asymmetric in 2 patients. In each patient, loss of retinal function correlated with structural changes in the outer retina. AOSLO showed focal cone loss in most patients, although in 1 patient with central vision loss such change was absent. In another patient, structural and functional analyses suggested that cones had degenerated but rods remained. Anti-retinal antibody activity against a ∼45 kd antigen was detected in 1 of the patients; the other 3 patients showed no evidence of abnormal anti-retinal antibodies.

Conclusions: Focal abnormalities of retinal structure correlated with vision loss in patients with AZOOR. High-resolution imaging can localize and demonstrate the extent of outer retinal abnormality in AZOOR patients.

Trial registration: ClinicalTrials.gov NCT00254605.

Copyright © 2012 Elsevier Inc. All rights reserved.

Figures

Figure 1. Acute Zonal Occult Outer Retinopathy

Patient 1, right eye; similar findings were present in the left eye (not shown). (Top left) The fundus examination was normal. (Top right) Parafoveal visual field (VF) defects with normal foveal sensitivities. (Middle) The multifocal electroretinographic first-order response traces, displayed in field view, reveal a discrete region, 50 temporal to fixation, of abnormally reduced response densities with delayed timing. (Bottom) Adaptive optics scanning laser ophthalmoscopy (AOSLO) images superimposed on an infrared fundus image reveal abnormal cone reflectivity in regions corresponding to the visual field defects and reduced multifocal electroretinography (mfERG) responses. The composite AOSLO image, which spans approximately 7.7×4.6 0, shows areas of reduced cone reflectivity around the foveal center, but otherwise contiguous cones with normal spacing (white circles). The insets, indicated by the black rectangles on the AOSLO montage, highlight retinal regions with contiguous cone coverage interspersed with areas of reduced retinal reflectivity. The lower insets show distinct transitions between normally-reflecting cones and reduced reflectance regions with less obvious cone mosaics. The left inset with black circles surrounding it demonstrates a retinal region with abnormal cone spacing. The spectral domain optical coherence tomography (SDOCT) scan (green line indicates scan location) shows irregularities in the inner segment/outer segment (IS/OS) junction corresponding with reduced reflectivity of cones. External limiting membrane (ELM) and IS/OS junction layers are labeled. The most affected region of the b-scan is indicated by the white line. Areas of reduced cone reflectivity correspond to regions of reduced sensitivity on the visual field test. Scale bar is 10.

Figure 2. Acute Zonal Occult Outer Retinopathy

Patient 2, left eye. (Top left) Mild retinal pigment epithelium (RPE) hypopigmentation was present temporal to the fovea. (Top right) Paracentral 100 scotoma nasal to fixation with normal foveal sensitivity. (Middle) The multifocal electroretinographic first-order response traces, displayed in field view, reveal a discrete area of reduced response density with delayed timing from 5-200 nasal to fixation. The area of reduced function corresponds to the paracentral scotoma present on VF testing and the retinal region with affected cone spacing. (Bottom) The AOSLO image, which spans approximately 8.9×2.40, is superimposed on an infrared fundus image (scale bar is 10). Cone spacing and coverage are normal (white circles) in all areas except locations near the relative scotoma (demarcated by the long white arrow), within which no cones are visible. The large inset (black rectangle) highlights the retinal region of normal cone spacing transitioning into abnormal or sparse cone spacing (black circles). The smaller insets (white squares) show a transition from cones to a localized region of hexagonal cells (white arrows) in addition to a localized retinal region with tightly packed cells, suspected to be rods.. The retinal region where RPE cells were observed is different from the region noted with presumed rods. The SDOCT scan (location indicated by the green line on the background image) shows reduced reflectance of the IS/OS junction within the relative scotoma. The inset above the SDOCT b-scan highlights the reflectance change.

Figure 3. Acute Zonal Occult Outer Retinopathy

(Top) Kinetic perimetry for patient 2, left eye. (Left) Two-color dark-adapted Goldmann kinetic field isopters. The isopter for the V3c long-wavelength stimulus target (red solid line) and the isopter for the V3̅c short- wavelength stimulus target (blue solid line) are superimposed. The isopter for the II3c long- wavelength stimulus target and the isopter for the II3̅c short- wavelength stimulus target (not shown) were also superimposed. In these rod-mediated tests, the scotoma is absent and both red and blue stimuli were seen as achromatic, although the patient reported the blue targets to appear “blurry or dimmer” in the region of the scotoma. (Right) Light-adapted, Goldmann kinetic field isopters obtained by using a white target stimulus shows full peripheral fields with the II3c and V3c targets; the I4e stimulus shows the scotoma. (Bottom) Dark-adapted two-color fundus-guided microperimetry for patient 2, left eye. The data from microperimetry is superimposed onto a fundus image. (Top) Dark adapted blue (Blue DA) sensitivities were normal throughout the regions tested (background illuminance of 0cd/m2, 200 ms Goldmann V blue stimulus, 2.0 neutral density (ND) filter. (Bottom) Dark adapted red (Red DA) sensitivities showed a dense scotoma beginning about 3 degrees temporal to fixation (background illuminance of 0cd/m2, 200 ms Goldmann V red stimulus, 1.0 ND filter). The difference between Blue DA and Red DA sensitivity values for each retinal location in the region of scotoma was at least 8dB, demonstrating rod-mediated sensitivity in the scotomatous region.

Figure 4. Acute Zonal Occult Outer Retinopathy

Patient 3, right eye. (Top left) The composite AOSLO image superimposed on an infrared fundus image reveals normal cone spacing and coverage (white circles) throughout the macula in the affected right eye despite the central scotoma. Two retinal locations indicated slightly abnormal cone spacing (black circles) but an otherwise contiguous cone mosaic. The composite image spans approximately 6.6×8.250 (scale bar is 10). The smaller AOSLO montage toward the disc indicates the location of the preferred retinal locus for fixation. (Center left) The magnified AOSLO montage is indicated by the black inset. The black dot in the inset is the location of the anatomical fovea. The SDOCT scan (green line indicates scan location) shows an uninterrupted IS/OS junction layer corresponding to the central region of scotoma. (Bottom left) SDOCT scans of the affected right eye (top) and the normal left eye (bottom). The left eye has been flipped horizontally for comparison purposes. ELM and IS/OS junction layers are labeled. The symptomatic eye shows attenuation of the outer nuclear and inner retinal layers compared to the contralateral eye. The laminar appearance of the optical components of the photoreceptors shows normal reflectance of the IS/OS junction across the macula, with subtle abnormalities of the OS/RPE junction. (Top right) Humphrey visual field (HVF) 30-2 at presentation (left) and 10-2 3 months later (right) reveals the initial temporal visual field defect decreasing in size, resulting in a central scotoma 60 in diameter over 3 months, which persisted 2 years after symptoms onset; foveal sensitivity was reduced by at least 3.5 log units. (Center right) The data from microperimetry is superimposed into fundus image. Microperimetry using a white background and a white Goldmann III 200 ms stimulus reveals at least 2 log units sensitivity loss in the central 40 in diameter. (Bottom right) The mfERG first-order responses displayed in field view also reveal unilateral reduced response densities centrally corresponding with the HVF defect.

Figure 5. Acute Zonal Occult Outer Retinopathy

Patient 4, right eye. (Top left) The composite AOSLO image, which spans approximately 7.7×70 (scale bar is 10) is superimposed on an infrared (IR) SLO fundus image. The AOSLO image shows a region of abnormal cone structure within the macula. The preferred retinal locus for fixation is superior to the anatomical fovea, labeled with a small black circle. Cones at the edges of the AOSLO field have lower density than normal (black circles). The locations of the insets are indicated by the black rectangles on the AOSLO montage. The lower left inset over the foveal center reveals sparse, irregularly-arranged cones and hexagonal cells consistent with RPE cells. A detail of the RPE cells is shown in the upper left inset. The right inset shows the transition from absence to presence of regular cone mosaics, albeit with reduced density. The SDOCT scan (location indicated by green line on the IR fundus image) indicates disruption and loss of the IS/OS junction in the central macula along with thinning of the outer nuclear layer. (Bottom left) SDOCT 12 months after initial presentation shows further loss of the IS/OS junction and outer segment layer, indicating progressive loss of the optical components of the photoreceptors in the macula. ELM and IS/OS junction layers are labeled. (Top right) Reduced visual acuity of 20/200 corresponded to a 40-diameter central scotoma with reduced foveal sensitivity of 18 dB (normal > 34 dB). (Top right) RPE depigmentation was present in the fovea. (Center right) Fundus-guided microperimetry using a white background and a white Goldmann III 200 ms stimulus shows reduced sensitivities by 1–2 log units in the central 2 degrees. Similar results were observed in the left eye (not shown). (Bottom right) Multifocal electroretinographic first-order response densities are reduced in the central 5–10 degrees.