Detecting progression of acute zonal occult outer retinopathy (AZOOR) with optical coherence tomography angiography: A case report.

CLINICAL CASE: A 48-year-old woman with persistent superotemporal scotomas and photopsias for 2 months, and depigmented zones in the retina of both eyes with a trizonal pattern on multimodal imaging. Brain magnetic resonance imaging, positron emission tomography, antiretinal antibodies, immunological, infectious and tumor markers tests were negative, thus acute zonal occult outer retinopathy was diagnosed. Patient was treated with adalimumab. Nevertheless, 19 months later symptoms increased, and progression was detected on optic coherence tomography angiography, as well as in Humphrey visual field test and electroretinogram, thus, mycophenolate mofetil was added showing improvement and stabilization of the disease in a 4-year follow-up. DISCUSSION: Optic coherence tomography angiography may be a potential tool to monitor progression and response to treatment in addition to other imaging modalities in acute zonal occult outer retinopathy, and the combination of adalimumab and mycophenolate may be useful in recurrent disease.

Highly accurate retinotopic maps of the physiological blind spot in human visual cortex.

The physiological blind spot is a naturally occurring scotoma corresponding with the optic disc in the retina of each eye. Even during monocular viewing, observers are usually oblivious to the scotoma, in part because the visual system extrapolates information from the surrounding area. Unfortunately, studying this visual field region with neuroimaging has proven difficult, as it occupies only a small part of retinotopic cortex. Here, we used functional magnetic resonance imaging and a novel data-driven method for mapping the retinotopic organization in and around the blind spot representation in V1. Our approach allowed for highly accurate reconstructions of the extent of an observer's blind spot, and out-performed conventional model-based analyses. This method opens exciting opportunities to study the plasticity of receptive fields after visual field loss, and our data add to evidence suggesting that the neural circuitry responsible for impressions of perceptual completion across the physiological blind spot most likely involves regions of extrastriate cortex-beyond V1.

Visual Field Characteristics in East Asian Patients With Occult Macular Dystrophy (Miyake Disease): EAOMD Report No. 3.

Purpose: The purpose of this study was to investigate the perimetric features and their associations with structural and functional features in patients with RP1L1-associated occult macular dystrophy (OMD; i.e. Miyake disease). Methods: In this international, multicenter, retrospective cohort study, 76 eyes of 38 patients from an East Asian cohort of patients with RP1L1-associated OMD were recruited. Visual field tests were performed using standard automated perimetry, and the patients were classified into three perimetric groups based on the visual field findings: central scotoma, other scotoma (e.g. paracentral scotoma), and no scotoma. The association of the structural and functional findings with the perimetric findings was evaluated. Results: Fifty-four eyes (71.1%) showed central scotoma, 14 (18.4%) had other scotomata, and 8 (10.5%) had no scotoma. Central scotoma was mostly noted in both eyes (96.3%) and within the central 10 degrees (90.7%). Among the three perimetric groups, there were significant differences in visual symptoms, best-corrected visual acuity (BCVA), and structural phenotypes (i.e. severity of photoreceptor changes). The central scotoma group showed worse BCVA often with severe structural abnormalities (96.3%) and a pathogenic variant of p.R45W (72.2%). The multifocal electroretinogram (mfERG) groups largely corresponded with the perimetric groups; however, 8 (10.5%) of 76 eyes showed mfERG abnormalities preceding typical central scotoma. Conclusions: The patterns of scotoma with different clinical severity were first identified in occult macular dystrophy, and central scotoma, a severe pattern, was most frequently observed. These perimetric patterns were associated with the severity of BCVA, structural phenotypes, genotype, and objective functional characteristics which may precede in some cases.

Intrasession and Intersession Reproducibility of Artificial Scotoma pRF Mapping Results at Ultra-High Fields.

Functional magnetic resonance imaging (fMRI) combined with population receptive field (pRF) mapping allows for associating positions on the visual cortex to areas on the visual field. Apart from applications in healthy subjects, this method can also be used to examine dysfunctions in patients suffering from partial visual field losses. While such objective measurement of visual deficits (scotoma) is of great importance for, e.g., longitudinal studies addressing treatment effects, it requires a thorough assessment of accuracy and reproducibility of the results obtained. In this study, we quantified the reproducibility of pRF mapping results within and across sessions in case of central visual field loss in a group of 15 human subjects. We simulated scotoma by masking a central area of 2° radius from stimulation to establish ground-truth conditions. This study was performed on a 7T ultra-high field MRI scanner for increased sensitivity. We found excellent intrasession and intersession reproducibility for the pRF center position (Spearman correlation coefficients for x, y: >0.95; eccentricity: >0.87; polar angle: >0.98), but only modest reproducibility for pRF size (Spearman correlation coefficients around 0.4). We further examined the scotoma detection performance using an automated method based on a reference dataset acquired with full-field stimulation. For the 2° artificial scotoma, the group-averaged scotoma sizes were estimated at between 1.92° and 2.19° for different sessions. We conclude that pRF mapping of visual field losses yields robust, reproducible measures of retinal function and suggest the use of pRF mapping as an objective method for monitoring visual deficits during therapeutic interventions or disease progression.

Investigation of progression pattern and associated risk factors in glaucoma patients with initial paracentral scotomas using Humphrey 10-2.

Central visual field (VF) progression could directly threaten patientss visual function compared to glaucomatous damage. This study was designed to investigate visual field (VF) progression pattern and associated risk factors including optical coherence topography angiographic (OCT-A) findings in glaucoma patients with initial paracentral scotoma. This prospective, observational study included 122 eyes presenting as initial paracentral scotomas with serial 24-2 and 10-2 VF tests at the glaucoma clinic of Seoul St Mary's Hospital between November 2017 and August 2020. The participants underwent at least 5 serial VF exams and OCT-A at baseline. Numerical values of the initial and final 10-2 VF tests were averaged for each VF test point using the total deviation map. Innermost 10-2 VF progression was defined as three or more new contiguous points at the central 12 points on 10-2 VF. Other clinical characteristics were collected including history of disc hemorrhage and vessel density (VD) was measured from OCT-A images. Linear regression analysis was performed to obtain the change of mean deviation and a cut-off for progression was defined for both 24-2 and 10-2 VFs. The average total deviation maps of the initial 10-2 VF tests shows initial paracentral scotoma located in the superior region in an arcuate pattern that was deep in the 4°-6° region above fixation. This arcuate pattern was more broadly located in the 4°-10° region in the primary open-angle glaucoma (POAG) group, while it was closer to fixation in 0°-4° region in the normal-tension glaucoma (NTG) group. The final average map shows deepening of scotomas in the 4°-10° region in POAG, which deepened closer to the region of fixation in NTG. The diagnosis of NTG (ß 1.892; 95% CI 1.225-2.516; P = 0.035) and lower choroidal VD in the peripapillary atrophy (PPA) region (ß 0.985; 95% CI 0.975 to 0.995; P = 0.022) were significantly related to innermost 10-2 VF progression. Initial paracentral scotomas in NTG tended to progress closer to the region of fixation, which should be monitored closely. Important progression risk factors related to paracentral scotoma near the fixation were the diagnosis of NTG and reduced choroidal VD in the ß-zone PPA region using OCT-A. We should consider vascular risk factors in NTG patients presenting with initial paracentral scotoma to avoid vision threatening progression of glaucoma.

Mapping the binocular scotoma in macular degeneration.

When the scotoma is binocular in macular degeneration (MD), it often obscures objects of interest, causing individuals to miss information. To map the binocular scotoma as precisely as current methods that map the monocular scotoma, we propose an iterative eye-tracker method. Study participants included nine individuals with MD and four age-matched controls. We measured the extent of the monocular scotomata using a scanning laser ophthalmoscope/optical coherence tomography (SLO/OCT). Then, we precisely mapped monocular and binocular scotomata with an eye tracker, while fixation was monitored. Participants responded whenever they detected briefly flashed dots, which were first presented on a coarse grid, and then at manually selected points to refine the shape and edges of the scotoma. Monocular scotomata measured in the SLO and eye tracker are highly similar, validating the eye-tracking method for scotoma mapping. Moreover, all participants used clustered fixation loci corresponding to their dominant preferred fixation locus. Critically, for individuals with binocular scotomata, the binocular map from the eye tracker was consistent with the overlap of the monocular scotoma profiles from the SLO. Thus, eye-tracker-based perimetry offers a reliable and sensitive tool for measuring both monocular and binocular scotomata, unlike the SLO/OCT that is limited to monocular viewing.

Functional Relevance of Hyper-Reflectivity in Macular Telangiectasia Type 2.

Purpose: The purpose of this study was to quantify hyper-reflective lesions on en face optical coherence tomography (OCT) and study its functional relevance in macular telangiectasia type 2 (MacTel). Design: This was a retrospective, cross-sectional cohort study. Methods: Baseline image and functional data from participants of a phase II clinical trial (NCT01949324) that studied the effect of Ciliary Neurotrophic Factor in patients with MacTel were analyzed. The projection of hyper-reflectivity within different layers on OCT was used to generate an en face view and measure the en face size of hyper-reflectivity. Ellipsoid zone (EZ)-loss was additionally evaluated, and en face images were superimposed onto microperimetry sensitivity maps, allowing to estimate mean retinal sensitivity within areas displaying hyper-reflectivity and EZ-loss, respectively. Best-corrected visual acuity (BCVA) and reading speed were also analyzed. Results: Fifty-two eyes from 52 patients were analyzed. Hyper-reflectivity was present in 32 eyes (62%), and EZ-loss in 50 (96%) eyes. Mean lesion size was 0.11 mm² (range = 0.01-0.26) for hyper-reflectivity and 0.51 mm² (range = 0.02-1.34) for EZ-loss, and lesion sizes correlated strongly (Spearman r = 0.79, P < 0.001). Although both hyper-reflectivity and EZ-loss were associated with a significant decrease in retinal sensitivity, mean sensitivity thresholds differed significantly between lesions (0.9 dB vs. 16.3 dB; P < 0.001), indicating an almost complete loss of sensitivity in hyper-reflective areas. No correlations were found between the size of hyper-reflectivity and BCVA (r = 0.09) or reading speed (r = -0.17). Conclusions: En face OCT can be used to quantify the area of hyper-reflective lesions in MacTel. Hyper-reflectivity in MacTel is associated with severe functional impairment, leading to an almost complete loss of retinal sensitivity as observed on microperimetry.

DIMINUTIVE PARACENTRAL ACUTE MIDDLE MACULOPATHY LESION.

PURPOSE: To describe a transient positive scotoma and corresponding optical coherence tomography (OCT) structural and angiographic findings. METHODS: The patient was evaluated with a comprehensive ophthalmic examination to include OCT structural and angiographic imaging with two different instruments, the Zeiss Plex Elite and the Optovue RTVue XR Avanti. RESULTS: A 45-year-old man had a sudden onset of a positive scotoma in the visual field of the left eye. No abnormalities were noted by ophthalmoscopy or fundus photography. Optical coherence tomography angiography was performed to evaluate the macular perfusion status. With each instrument, a small hyperreflective area, 175 µm in diameter, was imaged in the inner nuclear layer. The OCT angiographic images suggested a small area of decreased perfusion in the deep capillary plexus. Except for the diminutive size, the lesion had an appearance suggestive of paracentral acute middle maculopathy. The symptoms lessened rapidly, and when examined 4 days later, the lesion was less hyperreflective. Two weeks after presentation, the positive scotoma was not present and there was no longer any hyperreflectivity in the inner nuclear layer. CONCLUSION: Detection of the lesion was aided by using OCT angiographic scans, which have a much higher scan density than conventional OCT evaluations. The diminutive abnormality was consistent with a paracentral acute middle maculopathy lesion, although smaller than those previously reported. Micro-paracentral acute middle maculopathy lesions should be considered in the differential diagnosis of positive scotomas.

Optical Coherence Tomography Findings in the Junctional Scotoma of Traquair.

ABSTRACT: A 43-year-old woman presented with a right-sided visual field defect in the right eye. The visual acuity was normal and there was a right relative afferent pupillary defect. Formal visual field testing revealed a junctional scotoma of Traquair. The fundus examination showed optic atrophy in the right eye and optical coherence tomography demonstrated unilateral band atrophy. Neuroimaging revealed a sellar and suprasellar cystic pituitary adenoma for which she underwent a transsphenoidal drainage. We demonstrate the clinical and radiographic features of the junctional scotoma of Traquair and describe the differentiating features vs the junctional scotoma.

Abnormal Visual Function Outside the Area of Atrophy Defined by Short-Wavelength Fundus Autofluorescence in Stargardt Disease.

Purpose: To examine the extent of visual function abnormality outside the dark lesion on short-wavelength fundus autofluorescence (SW-AF), and its correlation with background SW-AF features and optical coherence tomography (OCT) in recessive Stargardt disease (STGD1). Methods: Forty-nine eyes of 25 participants in the ProgStar (the Natural History of the Progression of Atrophy Secondary to Stargardt Disease) study at our center were included. Patients underwent microperimetry (both threshold and dense scotoma mapping), OCT, SW-AF, and visual acuity testing. The Fisher's exact test, the χ2 test, and unpaired t-tests were used to analyze the data. Results: Of 40 eyes without central fixation, 33 (82%) placed fixation remote (most ≥5°) from the dense scotoma edge, despite good intervening retinal sensitivity. OCT findings accounted for the remote fixation in 75%. Eighteen (37%) of all 49 eyes had dense scotoma extending past the dark lesion border. OCT was not adequate to define the edge of the scotoma. Of the 49 eyes, 28 (57%) had the mottled background pattern, 10 (20%) had the uniform pattern, and 11 (22%) had the other pattern, with >75% of eyes in each pattern having remote fixation. The dense scotoma exceeded the dark lesion primarily in the mottled pattern. The two eyes of each patient were concordant in all features. Conclusions: Functional abnormalities in STGD1 extend past the SW-AF dark lesion. The disruption of the ellipsoid zone shows that photoreceptor abnormality extends peripheral to the dark lesion, and it explains in part the remote fixation pattern and the dense scotoma exceeding the dark lesion. This has implications for clinical trials for STGD1.

Contextual influences in the peripheral retina of patients with macular degeneration.

Macular degeneration (MD) is the leading cause of low vision in the elderly population worldwide. In case of complete bilateral loss of central vision, MD patients start to show a preferred retinal region for fixation (PRL). Previous literature has reported functional changes that are connected with the emergence of the PRL. In this paper, we question whether the PRL undergoes a use-dependent cortical reorganization that alters the range of spatial lateral interactions between low-level filters. We asked whether there is a modulation of the excitatory/inhibitory lateral interactions or whether contextual influences are well accounted for by the same law that describes the integration response in normal viewers. In a group of 13 MD patients and 7 age-matched controls, we probed contextual influences by measuring the contrast threshold for a vertical target Gabor, flanked by two collinear high-contrast Gabors. Contextual influences of the collinear flankers were indicated by the changes in contrast threshold obtained at different target-to-flanker distances (λs) relative to the baseline orthogonal condition. Results showed that MDs had higher thresholds in the baseline condition and functional impairment in the identification tasks. Moreover, at the shortest λ, we found facilitatory rather than inhibitory contextual influence. No difference was found between the PRL and a symmetrical retinal position (non-PRL). By pulling together data from MD and controls we showed that in the periphery this inversion occurs when the target threshold approach the flankers' contrast (about 1:3 ratio) and that for patients it does occur in both the PRL and a symmetrical retinal position (non-PRL). We conclude that contrary to previous interpretations, this modulation doesn't seem to reflect use-dependent cortical reorganization but rather, it might result from a reduction of contrast gain for the target that promotes target-flankers grouping.

Improved Diagnosis of Retinal Laser Injuries Using Near-Infrared Autofluorescence.

PURPOSE: To assess whether near infrared autofluorescence (NIR-AF) imaging is a useful imaging modality in the diagnosis of handheld laser retinal injuries. DESIGN: Retrospective observational case series. METHODS: Twelve patients identified to have handheld laser retinal injuries were included at 2 academic centers. Patients underwent ophthalmic assessment and retinal imaging including fundus photography, optical coherence tomography (OCT), conventional blue autofluorescence (B-AF), and NIR-AF imaging. RESULTS: In all cases, lesions consistent with retinal laser injury were detected by NIR-AF imaging. The lesions showed a characteristic appearance with central hyperfluorescence and surrounding hypofluorescence, although the number and extent of lesions varied between patients. Findings using other imaging modalities were variable: on color fundus photography these included localized pigmentary changes and on OCT imaging an ellipsoid zone interruption or outer nuclear layer changes. Only subtle changes were evident on B-AF imaging. Other macular conditions, such as poppers retinopathy or solar maculopathy, which may have similar findings on OCT imaging as laser damage, can be differentiated using NIR-AF imaging. CONCLUSION: An increased incidence of retinal injuries secondary to handheld lasers has been reported in recent years. We show that the diagnosis and full extent of retinal laser injuries is best demonstrated by NIR-AF, as other modalities give variable results. We propose that NIR-AF should be included when investigating patients suspected of macular injury secondary to exposure to handheld lasers.

Organization of area hV5/MT+ in subjects with homonymous visual field defects.

Damage to the primary visual cortex (V1) leads to a visual field loss (scotoma) in the retinotopically corresponding part of the visual field. Nonetheless, a small amount of residual visual sensitivity persists within the blind field. This residual capacity has been linked to activity observed in the middle temporal area complex (V5/MT+). However, it remains unknown whether the organization of hV5/MT+ changes following early visual cortical lesions. We studied the organization of area hV5/MT+ of five patients with dense homonymous defects in a quadrant of the visual field as a result of partial V1+ or optic radiation lesions. To do so, we developed a new method, which models the boundaries of population receptive fields directly from the BOLD signal of each voxel in the visual cortex. We found responses in hV5/MT+ arising inside the scotoma for all patients and identified two possible sources of activation: 1) responses might originate from partially lesioned parts of area V1 corresponding to the scotoma, and 2) responses can also originate independent of area V1 input suggesting the existence of functional V1-bypassing pathways. Apparently, visually driven activity observed in hV5/MT+ is not sufficient to mediate conscious vision. More surprisingly, visually driven activity in corresponding regions of V1 and early extrastriate areas including hV5/MT+ did not guarantee visual perception in the group of patients with post-geniculate lesions that we examined. This suggests that the fine coordination of visual activity patterns across visual areas may be an important determinant of whether visual perception persists following visual cortical lesions.

Correspondence between retinotopic cortical mapping and conventional functional and morphological assessment of retinal disease.

PURPOSE: The present study describes retinotopic mapping of the primary visual cortex using functional MRI (fMRI) in patients with retinal disease. It addresses the relationship between fMRI data and data obtained by conventional assessment including microperimetry (MP) and structural imaging. METHODS: Initial testing involved eight patients with central retinal disease (Stargardt disease, STGD) and eight with peripheral retinal disease (retinitis pigmentosa, RP), who were examined using fMRI and MP (Nidek MP-1). All had a secure clinical diagnosis supported by electrophysiological data. fMRI used population-receptive field (pRF) mapping to provide retinotopic data that were then compared with the results of MP, optical coherence tomography and fundus autofluorescence imaging. RESULTS: Full analysis, following assessment of fMRI data reliability criteria, was performed in five patients with STGD and seven patients with RP; unstable fixation was responsible for unreliable pRF measurements in three patients excluded from final analysis. The macular regions in patients with STGD with central visual field defects and outer retinal atrophy (ORA) at the macula correlated well with pRF coverage maps showing reduced density of activated voxels at the occipital pole. Patients with RP exhibited peripheral ORA and concentric visual field defects both on MP and pRF mapping. Anterior V1 voxels, corresponding to peripheral regions, showed no significant activation. Correspondence between MP and pRF mapping was quantified by calculating the simple matching coefficient. CONCLUSION: Retinotopic maps acquired by fMRI provide a valuable adjunct in the assessment of retinal dysfunction. The addition of microperimetric data to pRF maps allowed better assessment of macular function than MP alone. Unlike MP, pRF mapping provides objective data independent of psychophysical perception from the patient.