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.

Predictive masking of an artificial scotoma is associated with a system-wide reconfiguration of neural populations in the human visual cortex.

The visual brain has the remarkable capacity to complete our percept of the world even when the information extracted from the visual scene is incomplete. This ability to predict missing information based on information from spatially adjacent regions is an intriguing attribute of healthy vision. Yet, it gains particular significance when it masks the perceptual consequences of a retinal lesion, leaving patients unaware of their partial loss of vision and ultimately delaying diagnosis and treatment. At present, our understanding of the neural basis of this masking process is limited which hinders both quantitative modeling as well as translational application. To overcome this, we asked the participants to view visual stimuli with and without superimposed artificial scotoma (AS). We used fMRI to record the associated cortical activity and applied model-based analyzes to track changes in cortical population receptive fields and connectivity in response to the introduction of the AS. We found that throughout the visual field and cortical hierarchy, pRFs shifted their preferred position towards the AS border. Moreover, extrastriate areas biased their sampling of V1 towards sections outside the AS projection zone, thereby effectively masking the AS with signals from spared portions of the visual field. We speculate that the signals that drive these system-wide population modifications originate in extrastriate visual areas and, through feedback, also reconfigure the neural populations in the earlier visual areas.

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.

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.

Comparison of 10-2 and 24-2C Test Grids for Identifying Central Visual Field Defects in Glaucoma and Suspect Patients.

PURPOSE: To compare the ability of 24-2C and 10-2 test grids in measuring visual field global indices, identifying central visual field defects, and facilitating macular structure-function analysis with OCT scans in glaucoma and glaucoma suspect patients. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: One eye from 131 glaucoma and 57 glaucoma suspect patients recruited from a referral-only, university-based glaucoma clinic. METHODS: Each subject underwent perimetric testing using 24-2C SITA-Faster and 10-2 SITA-Fast in random order, and Cirrus OCT macular imaging (Ganglion Cell Analysis) for structure-function correlations. MAIN OUTCOME MEASURES: Visual field global indices (mean deviation, pattern standard deviation, binarized "cluster" pass/fail, and central mean sensitivity), number and proportion of visual field defects, and structure-function concordance with the Cirrus OCT deviation map following visual field location displacement for correspondence with underlying retinal ganglion cell position. RESULTS: Global indices (mean deviation, pattern standard deviation, and central mean sensitivity) were similar between both grids. The 10-2 detected more defects compared with the 24-2C (P < 0.0001 for all patients, P = 0.006 for glaucoma patients). This was preserved when analyzing the proportion of defects in the central visual field for all patients (P = 0.02) but was not significantly different for glaucoma patients (P = 0.051). The 10-2 identified more central "clusters" of 2+ contiguous points of deficit (P < 0.0001). Structure-function comparisons performed at locations where visual field and OCT test locations were colocalized revealed greater concordance of structural and functional deficits using the 10-2 (P < 0.0001). The 10-2 took a median of 201 seconds, and the 24-2C took a median of 154 seconds, corresponding to the different thresholding algorithms. CONCLUSIONS: The 24-2C and 10-2 test grids return similar global indices of visual field performance and proportionally similar amounts of central visual field loss. The additional points in the 10-2 grid return more "clusters" of defects and a greater rate of structure-function concordance compared with the 24-2C test grid. Thus, the 24-2C can identify the presence of a clustered central visual field defect using similar probability criteria, whereas the 10-2 may be more useful in comprehensively characterizing the defect and predicting central visual function.

Saccadic adaptation in the presence of artificial central scotomas.

Saccadic adaptation can occur over a short period of time through a constant adjustment of the saccade target during the saccade, resulting in saccadic re-referencing, which directs the saccade to a location different from the target that elicited the saccade. Saccade re-referencing could be used to help patients with age-related macular degeneration to optimally use their residual visual function. However, it remains unknown whether saccade adaptation can take place in the presence of central scotomas (i.e., without central vision). We tested participants in two experiments in a conventional double-step paradigm with a central gaze-contingent artificial scotoma. Experiment 1 (N = 12) comprised a backward adaptation paradigm with no scotoma control, visible, and invisible 3° diameter scotoma conditions. Experiment 2 (N = 13) comprised a forward adaptation paradigm with no scotoma control, invisible 2°, and 4° diameter scotoma conditions. In Experiment 1, we observed significant adaptation in both the visible and invisible scotoma conditions comparable to the control condition with no scotoma. This was the case even when the saccade landed such that the target was occluded by the scotoma. We observed that adaptation occurred based on peripheral viewing of the stepped target during the deceleration period. In Experiment 2, we found that both scotoma conditions showed adaptation again comparable to the control condition with no scotoma. We conclude that saccadic adaptation can occur with central scotomas, showing that it does not require central vision and can be driven primarily by peripheral retinal error.

Acute zonal occult outer retinopathy complex disease: Lessons learned about choroid, photoreceptors, and retinal function.

PURPOSE: Retinal photoreceptors layer integrity is considered essential to visual function. We report a case of acute zonal occult outer retinopathy (AZOOR) complex disease (namely AIBSE: acute idiopathic blind spot enlargement) in which apparently a full anatomic regeneration is not needed for a complete functional recovery. METHODS: Case report with multimodal imaging. REPORTS: Visual field recovery in the presence of photoreceptors layer disruption studied by means of Optical Coherence Tomography. Choroid and photoreceptors layer thickness thinned progressively during recovery. CONCLUSION: This case suggests that anatomical retinal integrity as shown by OCT does not always correspond to visual function. Our case highlights that a complete visual recovery can occur even when structural abnormalities are still observable.

Simultaneously performed combined 24-2 and 10-2 visual field tests in glaucoma.

Using either 24-2 or 10-2 visual field (VF) testing only is not enough to cover all the various types of glaucomatous VF defects. We investigated the performance of the combined 24-2 and 10-2 perimetry when conducted together and separately using the structure-function relationship. A total of 30 glaucoma patients with isolated peripheral nasal step, 37 patients with isolated paracentral scotoma, and 38 patients with both paracentral and nasal scotoma were included. To create the combined Humphrey VF test, a custom test pattern was established using the built-in custom point options, an example of the X, Y coordinate system. In glaucoma patients with peripheral nasal step, the superotemporal topographic structure-function relationship with peripapillary retinal nerve fiber layer (RNFL) thickness was superior in relation to the combined or 24-2 perimetry relative to the 10-2 perimetry (both P < 0.05). The combined VF test showed more favorable inferotemporal or inferonasal structure-function correlation with the corresponding ganglion cell-inner plexiform layer (GCIPL) thickness when compared with results gleaned using the 24-2 VF test (P < 0.05). Simultaneously performed 24-2 and 10-2 VF tests demonstrated a superior topographic structure-function relationship when compared with them separately performed in some sectors.

Long-term Outcome of Zonal Outer Retinopathy in Punctate Inner Choroidopathy or Multifocal Choroiditis.

Purpose: To report the long-term prognosis of punctate inner choroidopathy (PIC) or multifocal choroiditis (MFC) and associated zonal outer retinopathy (ZOR).Method: Retrospective study in patients with PIC/MFC and ZOR with a clinical follow-up of 4 years or longer.Results: There were 14 patients in this study (M: F = 11:3). All patients received systemic steroid therapy. The initial and final median logarithm of minimal angle of resolution of BCVA were 1.00 and 0.22 (p = .002). Ellipsoid zone recovery was noted in all patients. The median visual field loss improved from -6.38 dB to -3.41 dB (p = .035). The median of total area of PIC/MFC lesions enlarged from 6.82 mm2 to 8.77 mm2 (p = .005). Recurrent disease was noted in 4 eyes and maintenance steroid was needed in 3 eyes.Conclusion: With steroid therapy, most patients with PIC/MFC and ZOR had good visual prognosis.

Effectiveness of Low Vision Rehabilitation Using Microperimetric Acoustic Biofeedback Training in Patients with Central Scotoma.

PURPOSE: To evaluate the efficacy of visual rehabilitation with microperimeter biofeedback in patients with central scotoma. MATERIALS AND METHODS: 35 consecutive patients with central scotoma (17 age-related macular degeneration (AMD), 14 Stargardt disease, and 4 cone dystrophy) were included in the study. Visual acuity, reading performance by Minnesota Low Vision Reading Test (MNREAD), quality of life by 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25), and fixation analysis by MAIA microperimeter were evaluated before and 1 month after training. The rehabilitation program consisted of 10 training sessions of 10 minutes. RESULTS: The median best-corrected visual acuity (BCVA) was 0.80 logMAR (range 0.3 to 1.3 logMAR). Fifty-nine percent of patients with AMD developed a preferred retinal locus (PRL) nasal to the fovea, and 64% of the patients with Stargardt disease preferred a PRL superior to the fovea. The PRL location in 3 of 4 cone dystrophy patients was nasal to the fovea. The mean PRL distance from the fovea was 7.57 ± 3.61 degrees. Fixation stability improved with P1 values of 22.34 ± 11.81 versus 32.05 ± 18.79 (p = .003) and 95% bivariate contour ellipse area (BCEA) values of 41.6 versus 23.6 (p = .018) before and after training, respectively. There was a significant difference in reading acuity between before and after training (p = 0.008). The overall score and near activities score of NEI VFQ-25 were found to be increased at the end of the rehabilitation (p < 0.001). CONCLUSION: Rehabilitation with acoustic biofeedback in patients with central scotoma looks like a useful technique for improving fixation stability, reading performance and quality of life.

Long-Term Patient-Reported Outcomes of Visual Field Defects and Compensatory Mechanisms in Patients After Cerebral Hemispherectomy.

BACKGROUND: In cases of intractable epilepsy resistant to drug therapy, hemispherectomy is often the only treatment option to mitigate seizures; however, the true long-term subjective visual outcomes are relatively unexplored. In this study, we sought to determine and characterize patient-reported visual function years after hemispherectomy. METHODS: This was an observational study conducted on a large cohort of children with seizure disorder treated with cerebral hemispherectomy. An online survey was sent to parents with questions to assess subjective visual function with a variety of questions from presence of visual field defects after hemispherectomy, to improvement over time, compensatory mechanisms used, and development of strabismus. RESULTS: This survey was emailed to 248 parents of previously evaluated children who agreed to be re-surveyed, 48 (20%) of which responded. The average age at hemispherectomy was approximately 5 (±4) years, and the average time after hemispherectomy was 7 (±5) years. Thirty-nine patients (81%) were seizure-free after 1 surgery and 85% (n = 41) were seizure-free after ≥1 surgeries. Thirty-four (71%) experienced a visual field defect after surgery, but 25 (52%) experienced subjective improvement over time. Thirty-eight (79%) used compensatory mechanisms, such as head tilting, with 16 (33%) patients experiencing subjective improvement over time. Twenty-seven (56%) patients experienced a decrease in visual acuity after surgery with 12 (25%) experiencing subjective improvement over time. CONCLUSION: In a large cohort examining patient-reported visual outcomes years after hemispherectomy, most patients experienced strabismus and/or visual field defects. However, more than half reported improvements and compensatory mechanisms (exotropic strabismus and ipsilateral esotropic strabismus) over time, presumably to enhance visual field function. By exploring subjective visual and cognitive function, this paper uniquely characterizes patient-reported improvements over time, and provides motivation for larger longitudinal studies using more quantitative measures of visual function and improvement after hemispherectomy.

Three cases of Charles Bonnet Syndrome in patients with advanced glaucomatous visual field loss but preserved visual acuity.

PURPOSE: To describe three cases of Charles Bonnet syndrome (CBS) in glaucoma patients with preserved visual acuity. METHODS: Three glaucoma patients who had taken part in a recent CBS study were interviewed about their hallucinations. The patients underwent macular optical coherence tomography (OCT) of both eyes. The visual function was evaluated with visual field measurement (Humphrey visual field analyser) and visual acuity testing (Snellen scale). RESULTS: All three patients had preserved visual acuity (≥0.5 in both eyes) and at least one eye with advanced visual field defect (Mean Deviation worse than -12.00 decibel). They all reported vivid visual hallucinations with insight into the unreal nature of the hallucinations. CONCLUSION: Charles Bonnet syndrome can occur in glaucoma despite preserved visual acuity. Awareness of this relation is desirable among clinicians, as it will improve communication with patients.

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.

An Increased Choroidal Microvasculature Dropout Size is Associated With Progressive Visual Field Loss in Open-Angle Glaucoma.

PURPOSE: To investigate whether the choroidal microvasculature dropout (CMvD) increases in size over time among open-angle glaucoma (OAG) eyes presenting with CMvD at baseline and evaluate the association between longitudinal CMvD size increases and subsequent visual field (VF) progression. DESIGN: Retrospective cohort study. METHODS: This study enrolled 101 eyes from 101 consecutive patients with OAG with a localized CMvD and glaucomatous VF defects at baseline and a minimum 2-year follow-up. The angular circumference (AC) of the CMvD was determined from choroidal layer images using optical coherence tomography angiography at the baseline and final follow-up. Demographic and ocular characteristics, including the rate of retinal nerve fiber layer thickness loss and amount of CMvD AC increase during follow-up, were compared between OAG eyes with and without VF progression. Cox proportional hazard analysis was performed to identify the clinical factors associated with VF progression. The relationships between CMvD angular enlargement during follow-up and clinical factors were assessed. RESULTS: CMvD angular enlargement was found in 21.8% of patients while VF progression was observed in 26.7% of the OAG eyes with CMvD during a mean 2.52-year follow-up. OAG eyes with VF progression showed a significantly greater CMvD angular enlargement. A larger increase in the CMvD AC was an independent predictor of VF progression. CMvD AC changes were significantly correlated with the rates of VF deterioration. CONCLUSIONS: VF progression is significantly associated with a greater longitudinal increase in the CMvD AC in OAG eyes with CMvD. CMvD AC changes have significant correlations with the rate of VF loss.

Central Visual Field Defects in Patients with Distinct Glaucomatous Optic Disc Phenotypes.

PURPOSE: To investigate central visual field (VF) defects among 4 phenotypes of glaucomatous optic discs. DESIGN: Cross-sectional study. METHODS: Optic disc phenotypes were determined in eyes with definite or suspected glaucoma that had a 24-2 VF with mean deviation (MD) better than -12 dB and a 10-2 VF. 10-2 VFs were classified as abnormal based on a cluster criterion. Additionally, the average of the total deviation values at each 10-2 test point was compared by optic disc phenotype. RESULTS: The following 4 glaucomatous optic disc phenotypes were identified in 448 eyes of 309 patients: focal ischemic (FI) (n = 121); generalized cup enlargement (GE) (n = 109); myopic glaucoma (MY) (n = 66); and senile sclerotic (SS) (n = 152). Although 24-2 VF MD values were similar among optic disc phenotypes, GE eyes had higher 10-2 VF MD (P = .004), as well as lower 24-2 VF pattern standard deviations (PSD) (P < .001) and VF 10-2 PSD (P < .001) than the other phenotypes. The prevalence of an abnormal VF 10-2 was highest in FI eyes (78.5%) and lowest in GE eyes (50.5%) (P < .001). In glaucoma suspects, the prevalence of an abnormal 10-2 VF was highest in the MY eyes (31.2%) and FI eyes (23.5%) and lowest in GE eyes (8.6%). In mild glaucoma, the prevalence of abnormal 10-2 VF test results was highest in FI eyes (79.2%) and lowest in GE eyes (44.4%) (P = .013). CONCLUSIONS: The severity and prevalence of central VF loss varied among different glaucomatous optic disc phenotypes. Glaucomatous eyes with FI and MY optic disc phenotypes are more likely to have 10-2 VF loss, particularly in early disease, and especially may benefit from testing with both 10-2 and 24-2 VF tests.

We don't all look the same; detailed examination of peripheral looking strategies after simulated central vision loss.

Loss of central vision can be compensated for in part by increased use of peripheral vision. For example, patients with macular degeneration or those experiencing simulated central vision loss tend to develop eccentric viewing strategies for reading or other visual tasks. The factors driving this learning are still unclear and likely involve complex changes in oculomotor strategies that may differ among people and tasks. Although to date a number of studies have examined reliance on peripheral vision after simulated central vision loss, individual differences in developing peripheral viewing strategies and the extent to which they transfer to untrained tasks have received little attention. Here, we apply a recently published method of characterizing oculomotor strategies after central vision loss to understand the time course of changes in oculomotor strategies through training in 19 healthy individuals with a gaze-contingent display obstructing the central 10° of the visual field. After 10 days of training, we found mean improvements in saccadic re-referencing (the percentage of trials in which the first saccade placed the target outside the scotoma), latency of target acquisition (time interval between target presentation and a saccade putting the target outside the scotoma), and fixation stability. These results are consistent with participants developing compensatory oculomotor strategies as a result of training. However, we also observed substantial individual differences in the formation of eye movement strategies and the extent to which they transferred to an untrained task, likely reflecting both variations in learning rates and patterns of learning. This more complete characterization of peripheral looking strategies and how they change with training may help us understand individual differences in rehabilitation after central vision loss.

Combining fixation and lateral masking training enhances perceptual learning effects in patients with macular degeneration.

Macular degeneration (MD), a retinal disease affecting central vision, represents the leading cause of visual impairment in the Western world, and MD patients face severe limitations in daily activities like reading and face recognition. A common compensation strategy adopted by these patients involves the use of a region in the spared peripheral retina as a new fixation spot and oculomotor reference (preferred retinal locus, or PRL). Still, peripheral vision is characterized by poorer visual acuity, fixation stability, and larger crowding zones that further hinder processes like object recognition, visual search, and reading. Perceptual learning (PL) has been successfully used to improve visual acuity in mild visual conditions (e.g., presbyopia, amblyopia and myopia), but results in MD are less clear, often showing limited generalization of learning, unlike what is observed in a healthy population. A possible reason is the suboptimal fixation in the PRL that might prevent patients from processing the briefly presented training stimuli. Following this hypothesis, we trained five MD patients and four age- and eccentricity-matched controls with a protocol that combined contrast detection and a task previously used to train fixation stability. Results showed transfer of learning to crowding reduction, reading speed, and visual acuity in both MD patients and controls. These results suggest that in the case of central vision loss, PL training might benefit from the integration of oculomotor components to optimize the effect of training and promote transfer of learning to other visual functions.