Choroidal Detachment After Intravitreal Injection of Faricimab.

This case report discusses a diagnosis of choroidal detachment and suprachoroidal hemorrhage in a patient aged 70 years after an uneventful intravitreal injection of faricimab for neovascular age-related macular degeneration.

The Sensitivity of Ultra-Widefield Fundus Photography Versus Scleral Depressed Examination for Detection of Retinal Horseshoe Tears.

PURPOSE: Ultra-widefield (UWF) imaging is commonly used in ophthalmology in tandem with scleral depressed examinations (SDE) to evaluate peripheral retinal disease. Because of the increased reliance on this technology in tele-ophthalmology, it is critical to evaluate its efficacy for detecting the peripheral retina when performed in isolation. Therefore, we sought to evaluate UWF imaging sensitivity in detecting retinal horseshoe tears (HSTs). STUDY DESIGN: Retrospective clinical validity and reliability study. METHODS: A single-institutional retrospective analysis was performed on patients at the Shiley Eye Institute, University of California, San Diego. Patients with HSTs seen on SDE who underwent treatment with laser were included in the study. A total of 140 patients with HSTs in the right and/or left eyes met the inclusion criteria. Those with concomitant ruptured globes, retinal detachments, and vitreous hemorrhages were excluded. A total of 123 patients with 135 HSTs were included in the final analysis. The primary outcome was the number of HSTs detected by UWF imaging. A secondary outcome was HST location. Sensitivity was measured with respect to HST location, and statistical significance was calculated by Fisher exact testing. RESULTS: A total of 69 (51.1%) HSTs were visualized on UWF images and 66 (48.9%) were not visualized. The sensitivity of UWF imaging in capturing HSTs was 7 of 41 (17.1%), 8 of 25 (32.0%), 7 of 14 (50.0%), and 47 of 55 (85.5%) for the superior, inferior, nasal, and temporal quadrants, respectively. Sensitivities between HST visibility and location were statistically significant (P < .001). CONCLUSIONS: Nearly half of HSTs were missed by UWF imaging. This study demonstrates that UWF imaging alone is not sufficiently sensitive to exclude the presence of HSTs.

DIRECT MACULAR HOLE MANIPULATION RESULTS IN HIGH SUCCESS RATE IN SECONDARY MACULAR HOLE REPAIR.

PURPOSE: To investigate closure rates and functional outcomes of surgery for refractory and recurrent macular holes (MHs) in a real-world setting. METHODS: Retrospective review of secondary MH surgeries. RESULTS: A total of 72 eyes from 72 patients were included. Eyes had a mean of 1.51 surgeries before inclusion into this study with a mean MH size of 762 µ m and a mean baseline logarithm of the minimum angle of resolution best-corrected visual acuity of 1.11 (∼20/260 Snellen). Closure rates were 89.3% for tissue transplantation, 77.3% for internal limiting membrane (ILM) flaps, 92.9% for MH manipulation, and 12.5% for repeat ILM peeling ( P < 0.05). Best-corrected visual acuity changes in logarithm of the minimum angle of resolution from baseline to postoperative month six were +0.29 for ILM peeling alone (15 Early Treatment Diabetic Retinopathy Study letters worse), -0.39 for MH manipulation (20 Early Treatment Diabetic Retinopathy Study letters improved), -0.23 for tissue transplantation (13 Early Treatment Diabetic Retinopathy Study letters improved), and -0.2 for ILM flaps (10 Early Treatment Diabetic Retinopathy Study letters improved; P < 0.05). CONCLUSION: Secondary MH closure is possible using various surgical techniques with acceptable anatomical closure rates. Repeat ILM peeling is associated with the lowest closure rates and poorest functional results. To distinguish between techniques would require a large sample size of approximately 750 eyes.

Progression of Stargardt Disease as Determined by Fundus Autofluorescence Over a 24-Month Period (ProgStar Report No. 17).

PURPOSE: To estimate the progression rate of atrophic lesions in Stargardt disease derived from fundus autofluorescence (FAF). DESIGN: International, multicenter, prospective cohort study. METHODS: A total of 259 participants aged ≥6 years with disease-causing variants in the ABCA4 gene were enrolled from 9 centers and followed over a 24-month period. FAF images were obtained every 6 months, and areas of definitely decreased autofluorescence (DDAF) and decreased autofluorescence (DAF) were quantified. Progression rates were estimated from linear mixed models with time as the independent variable. RESULTS: A total of 488 study eyes of 259 participants (88.8% with both eyes) were enrolled and images from 432 eyes were followed for 24 months. The overall estimated progression of DDAF was 0.74 mm2/y (95% CI 0.64-0.85, P < .0001) and that of DAF was 0.64 mm2/y (95% CI 0.57-0.71) over a 24-month period in univariate analysis. Growth rates were strongly dependent on baseline lesion area. After square root transformation, the DDAF growth rate was not dependent on baseline lesion radius (P = .11), whereas the DAF growth rate was dependent (P < .0001). Genotype was not found to significantly impact the growth rate of DDAF or DAF lesions. CONCLUSIONS: FAF may serve as a convenient monitoring tool and suitable end point for interventional clinical trials that aim to slow disease progression. DDAF and DAF lesion sizes at baseline are strong predicting factors for lesion area growth and can be partially accounted for by square root transformation.

PATIENT WITH UNILATERAL CHOROIDAL AND SEROUS RETINAL DETACHMENT WITH A HISTORY OF TREATED PROSTATE CANCER AND UNTREATED SARCOIDOSIS.

BACKGROUND/PURPOSE: To report a case of unilateral choroidal detachment and serous retinal detachment in a patient with a history of untreated sarcoidosis. METHODS: Case report. The patient is a 67-year-old African American man with a history of nontreated sarcoidosis and prostate cancer. His prostate cancer was treated several years earlier with external beam radiation therapy. The patient presented with blurred visual acuity of 20/30 and floaters in the right eye. He was discovered to have several hypopigmented choroidal lesions, 360-degree choroidal detachment, and shallow serous retinal detachment in the right eye. RESULTS: The patient was treated with subtenons kenalog and oral prednisone with subsequent improvement of vision and resolution of choroidal and retinal detachment. CONCLUSION: Ocular sarcoidosis can involve any part of the eye and its adnexal tissues and may cause uveitis, episcleritis, scleritis, eyelid abnormalities, conjunctival granuloma, optic neuropathy, lacrimal gland enlargement, and orbital inflammation. Most patients with ophthalmic sarcoidosis have evidence of systemic involvement at the time of the initial examination and have bilateral ocular presentation. We present here the unique case of a 67-year-old man with unilateral 360-degree choroidal detachment and serous retinal detachment as an ocular presentation of sarcoidosis.

JUXTAPAPILLARY CAPILLARY RETINAL ANGIOMA AND EPIRETINAL MEMBRANE MANAGEMENT IN A MONOCULAR PATIENT WITH VON HIPPEL-LINDAU SYNDROME.

PURPOSE: To report a case of von Hippel-Lindau syndrome in a monocular patient with progressive vision loss due to a juxtapapillary capillary retinal angioma and an epiretinal membrane (ERM) formation. PATIENT: We describe a 37-year-old white male patient with von Hippel-Lindau syndrome who presented for retinal evaluation. The right eye was blind with no light perception vision. The left eye had a best-corrected visual acuity of 20/30 and exhibited a peripheral capillary hemangioblastoma at 12 o'clock and a juxtapapillary capillary hemangioma with an ERM covering the fovea. The patient underwent two sessions of fluorescein-potentiated argon laser treatment to the peripheral capillary hemangioblastoma with initial stabilization of vision. After 18 months of follow-up, the ERM contracted causing decline in vision to 20/50. Intravitreal injection of bevacizumab was given without improvement in vision or distortion. Twenty-five-gauge pars plana vitrectomy with ERM peeling and internal limiting membrane removal was performed with immediate improvement in vision and distortion. CONCLUSION: This case suggests that pars plana vitrectomy is a reasonable treatment option for vision loss due to a juxtapapillary capillary retinal angioma and ERM formation.

Longitudinal Changes of Fixation Stability and Location Within 24 Months in Stargardt Disease: ProgStar Report No. 16.

PURPOSE: Stargardt disease type 1 (STGD1) is the most common macular dystrophy. The assessment of fixation describes an important dimension of visual function, but data on its progression over time are limited. We present longitudinal changes and investigate its usefulness for clinical trials. DESIGN: International, multicenter, prospective cohort study. METHODS: Included were 239 individuals with genetically confirmed STGD1 (one or more disease-causing ATP binding cassette subfamily A member 4 [ABCA4] variant). We determined the fixation stability (FS) using 1 SD of the bivariate contour ellipse area (1 SD-BCEA) and fixation location (FL) using the eccentricity of fixation from the fovea during five study visits every 6 months. RESULTS: At baseline, 239 patients (105 males [44%]) and 459 eyes, with a median age of 32 years, were included. The baseline mean logBCEA was 0.70 ± 1.41 log deg2 and the mean FL was 6.25° ± 4.40°. Although the mean logBCEA did not monotonically increase from visit to visit, the overall yearly increase in the logBCEA was 0.124 log deg2 (95% CI, 0.063-0.185 log deg2). The rate of change was not different between the 2 years but increased faster in eyes without flecks outside of the vascular arcades and depended on baseline logBCEA. FL did not change statistically significantly over time. CONCLUSIONS: Fixation parameters are unlikely to be sensitive outcome measures for clinical trials in STGD1 but may provide useful ancillary information in selected cases to longitudinally describe and understand an eye's visual function.

The Progression of Stargardt Disease Using Volumetric Hill of Vision Analyses Over 24 Months: ProgStar Report No.15.

PURPOSE: To report the yearly rate of change in macular function in patients with Stargardt disease type 1 (STGD1) over 24 months and to establish a new volumetric visual function index for use in clinical trials investigating the efficacy on retinal sensitivity. METHODS: Design: International, multicenter, prospective cohort study with 5 study visits every 6 months over 24 months. PARTICIPANTS: A total of 233 individuals with genetically confirmed STGD1 (≥1 disease-causing ABCA4 variant). MAIN OUTCOME MEASURES: The total volume (VTOT) beneath the sensitivity surface of a 3-D model of the hill of vision and mean sensitivity (MS) derived from mesopic microperimetry performed with a white stimulus. Changes of VTOT over time and its correlation with the ABCA4 genotype and baseline features. RESULTS: At baseline, 440 eyes (233 patients) with a mean (SD) age of 33.7 (15.0) years, mean (SD) visual acuity of 46.08 (16.03) ETDRS letters were analyzed with an average VTOT of 0.91 decibel-steradian (dB-sr) and an MS of 10.73 dB. The overall mean rate of decrease in sensitivity [95% confidence interval] was 0.077 [0.064, 0.090] dB-sr/y for VTOT and 0.87 [0.72, 1.02] dB/year for MS. The progression rate of VTOT depended on baseline visual function (0.029 dB-sr/year for low and 0.120 dB-sr/year for high baseline VTOT; P < .001) and exhibited a difference in the first vs second year of follow-up (0.065 dB-sr/year vs 0.089 dB-sr/year, respectively; P < .001). The absence of pigmentary abnormalities of the retinal pigment epithelium at baseline was found to be associated with a faster progression rate (P < .001), whereas a significant association with the genotype was not detected (P = .7). CONCLUSION: In STGD1, both microperimetric outcomes demonstrate statistically significant and clinically meaningful changes after relatively short follow-up periods. Volumetric modeling may be useful in future interventional clinical trials that aim to improve retinal sensitivity or to slow down its decline and for structure-function correlations.

Longitudinal Microperimetric Changes of Macular Sensitivity in Stargardt Disease After 12 Months: ProgStar Report No. 13.

Importance: Functional end points for clinical trials investigating the efficacy of emerging treatments for Stargardt disease type 1 (STGD1) are needed. Objective: To assess the yearly rate of change of macular function in patients with STGD1 using microperimetry. Design, Setting, and Participants: This multicenter prospective cohort study was conducted in an international selection of tertiary referral centers from October 21, 2013, to February 15, 2017. The study included participants with ABCA4-related STGD1 who were enrolled in the Natural History of the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) study at baseline. Data were analyzed from February 16, 2017, to December 1, 2019. Exposure: ABCA4-related STGD1 with a minimum lesion size on fundus autofluorescence and a minimum visual acuity. Main Outcomes and Measures: Changes in overall macular sensitivity (MS), deep scotoma count, number of points that tested normal, and location-specific sensitivity changes. Results: Among the 359 eyes from 200 patients (87 [43.5%] men; mean [SD] age, 33.3 [15.2] years) who underwent microperimetry examination graded at baseline and month 12, the mean (SD) yearly change in MS was -0.68 (2.04) dB (95% CI, -0.89 to -0.47 dB; P < .001), and deep scotoma points increased by a mean (SD) of 1.56 (5.74) points per year. The points with sensitivity of 12 dB or higher decreased in sensitivity by a mean (SD) of -3.01 (9.84) dB (95% CI, -4.03 to -1.99 dB; P < .001). The mean (SD) yearly change in MS was not significantly different between the eyes with a grading of good or fair pattern placement at both visits (-0.67 [2.1] dB) and the eyes with a poor pattern placement during at least 1 visit (-0.64 [2.2] dB) (P = .91). Conclusions and Relevance: This study showed that MS and the number of deep scotoma points had measurably changed after follow-up of approximately 1 year. Microperimetry may serve as a useful functional outcome parameter for clinical trials aimed at slowing the progression of STGD1.

The Effect of Attention on Fixation Stability During Dynamic Fixation Testing in Stargardt Disease.

PURPOSE: Sensitive, reproducible visual function biomarkers are necessary to evaluate the efficacy of emerging treatments for Stargardt disease type 1 in clinical trials. We previously demonstrated that fixation stability may serve as a secondary outcome parameter for visual function loss. However, the test duration and protocol have an unknown effect on the assessment of fixation stability. Here, we hypothesize that separate fixation testing with a single target is different from combined fixation testing using the same target with simultaneous perimetry testing. DESIGN: International, multicenter, prospective, cross-sectional study. METHODS: Microperimetry data from the international, multicenter, prospective Progression of Atrophy Secondary to Stargardt Disease (ProgStar, NCT01977846) study were analyzed. Patients underwent various types of fixation testing including static testing and dynamic testing, and a duration-corrected dynamic test was generated (30sEpoch). RESULTS: A total of 437 eyes from 235 patients were included (mean age, 33.8 ± 15.1 years; 55.3% female). The mean 1SD-BCEA (bivariate contour ellipse area), which is the smallest ellipse encompassing 1 standard deviation of all fixation events, was smaller for the static fixation test compared to the 30sEpoch (4.5 ± 6.9 deg2 vs 5.3 ± 7.0 deg2; P = .02) and the number of points within both the 2-degree and 4-degree circles was larger (P < .0001). CONCLUSIONS: Our results suggest that differences in static and dynamic assessment of fixation stability are dependent not only on different test durations but also on the testing protocol of a single fixation target vs fixation target plus simultaneous perimetry testing and provide information on the conduct of fixation testing for clinical trials.

Faster Sensitivity Loss around Dense Scotomas than for Overall Macular Sensitivity in Stargardt Disease: ProgStar Report No. 14.

PURPOSE: Mean sensitivity (MS) derived from a standard test grid using microperimetry is a sensitive outcome measure in clinical trials investigating new treatments for degenerative retinal diseases. This study hypothesizes that the functional decline is faster at the edge of the dense scotoma (eMS) than by using the overall MS. DESIGN: Multicenter, international, prospective cohort study: ProgStar Study. METHODS: Stargardt disease type 1 patients (carrying at least 1 mutation in the ABCA4 gene) were followed over 12 months using microperimetry with a Humphrey 10-2 test grid. Customized software was developed to automatically define and selectively follow the test points directly adjacent to the dense scotoma points and to calculate their mean sensitivity (eMS). RESULTS: Among 361 eyes (185 patients), the mean age was 32.9 ± 15.1 years old. At baseline, MS was 10.4 ± 5.2 dB (n = 361), and the eMS was 9.3 ± 3.3 dB (n = 335). The yearly progression rate of MS (1.5 ± 2.1 dB/year) was significantly lower (ß = -1.33; P < .001) than that for eMS (2.9 ± 2.9 dB/year). There were no differences between progression rates using automated grading and those using manual grading (ß = .09; P = .461). CONCLUSIONS: In Stargardt disease type 1, macular sensitivity declines significantly faster at the edge of the dense scotoma than in the overall test grid. An automated, time-efficient approach for extracting and grading eMS is possible and appears valid. Thus, eMS offers a valuable tool and sensitive outcome parameter with which to follow Stargardt patients in clinical trials, allowing clinical trial designs with shorter duration and/or smaller cohorts.

A Workshop on Measuring the Progression of Atrophy Secondary to Stargardt Disease in the ProgStar Studies: Findings and Lessons Learned.

The Progression of Atrophy Secondary to Stargardt Disease (ProgStar) studies were designed to measure the progression of Stargardt disease through the use of fundus autofluorescence imaging, optical coherence tomography, and microperimetry. The overarching objectives of the studies were to document the natural course of Stargardt disease and identify the most appropriate clinical outcome measures for clinical trials assessing the efficacy and safety of upcoming treatments for Stargardt disease. A workshop organized by the Foundation Fighting Blindness Clinical Research Institute was held on June 11, 2018, in Baltimore, MD, USA. Invited speakers discussed spectral-domain optical coherence tomography, fundus autofluorescence, and microperimetry methods and findings in the ProgStar prospective study. The workshop concluded with a panel discussion of optimal endpoints for measuring treatment efficacy in Stargardt disease. We summarize the workshop presentations in light of the most current literature on Stargardt disease and discuss potential clinical outcome measures and endpoints for future treatment trials.

Scotopic Microperimetric Assessment of Rod Function in Stargardt Disease (SMART) Study: Design and Baseline Characteristics (Report No. 1).

PURPOSE: To describe the study design and characteristics at first visit of participants in the longitudinal Scotopic Microperimetric Assessment of Rod Function in Stargardt Disease (SMART) study. METHODS: Scotopic microperimetry (sMP) was performed in one designated study eye in a subset of participants with molecularly proven ABCA4-associated Stargardt disease (STGD1) enrolled in a multicenter natural history study (ProgStar). Study visits were every 6 months over a period ranging from 6 to 24 months, and also included fundus autofluorescence (FAF). RESULTS: SMART enrolled 118 participants (118 eyes). At the first visit of SMART, the mean sensitivity in mesopic microperimetry was 11.48 (±5.05; range 0.00-19.88) dB and in sMP 11.25 (±5.26; 0-19.25) dB. For FAF, all eyes had a lesion of decreased autofluorescence (mean lesion size 3.62 [±3.48; 0.10-21.46] mm2), and a total of 76 eyes (65.5%) had a lesion of definitely decreased autofluorescence with a mean lesion size of 3.46 (±3.60; 0.21-21.46) mm2. CONCLUSIONS: Rod function is impaired in STGD1 and can be assessed by sMP. Testing rod function may serve as a potential outcome measure for future clinical treatment trials. This is evaluated in the SMART study.

Progression of retinitis pigmentosa on multimodal imaging: The PREP-1 study.

IMPORTANCE: It is important to establish reliable outcome measures to detect progression in retinitis pigmentosa (RP). BACKGROUND: To evaluate progression of RP using multimodal imaging, including spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF) and microperimetry (MP). DESIGN: Retrospective longitudinal study at a tertiary teaching hospital. PARTICIPANTS: 205 eyes of 106 patients with RP with 1 to 5 y of follow-up. METHODS: Demographics and visual acuity (VA) were recorded, and each modality was graded at baseline and every annual follow-up. SD-OCT was graded for the width of ellipsoid zone (EZ), FAF was graded for the diameter and area of the hyperautofluorescent ring (if present), and MP was graded for mean, central and paracentral sensitivity. Spearman's correlation was used to measure correlations at baseline. Mixed effects models were used to estimate the annual change of each parameter, adjusted for disease duration. MAIN OUTCOME MEASURES: Rate of progression. RESULTS: The median VA at baseline was 75 letters and was positively correlated with mean and central sensitivity (r: 0.372 and 0.394; P = 0.01 for both). All parameters (except paracentral sensitivity) were strongly correlated with each other (r: 0.673-0.991; P < 0.001 for all). The annual rates of change for each parameter were as follows: VA, -2.3 letters (P < 0.001); EZ, -151 µm (P < 0.001); ring diameter, -132 µm (P < 0.001); ring area, -0.4 mm2 (P < 0.001); mean sensitivity, -0.3 dB (P < 0.001); central sensitivity, -0.7 dB (P < 0.001); paracentral sensitivity, -0.4 dB (P < 0.001). CONCLUSIONS AND RELEVANCE: Structural and functional measures are well correlated in RP and can reliably measure disease progression within the course of a year.

The Progression of the Stargardt Disease Type 4 (ProgStar-4) Study: Design and Baseline Characteristics (ProgStar-4 Report No. 1).

BACKGROUND/AIMS: To describe the design and baseline characteristics of patients enrolled in the multicenter, prospective natural history study of Stargardt disease type 4. METHODS: Fifteen eligible patients aged 6 years and older at baseline, harboring disease-causing variants in the PROM1 gene, and with specified ocular lesions were enrolled. They were examined at baseline using a standard protocol, with 6 monthly follow-up visits for a 2-year period including best-corrected ETDRS visual acuity, spectral-domain optical coherence tomography, fundus autofluorescence (FAF), mesopic and scotopic microperimetry (MP). Areas of definitely decreased FAF (DDAF) and questionably decreased FAF were outlined and quantified on FAF images. RESULTS: Amongst the 15 patients (29 eyes) that were enrolled at 5 centers in the USA and Europe, 10 eyes (34.5%) had areas of DDAF with an average lesion area of 3.2 ± 3.5 mm2 (range 0.36-10.39 mm2) at baseline. The mean retinal sensitivity of the posterior pole derived from mesopic MP was 8.8 ± 5.8 dB. CONCLUSIONS: Data on disease progression in PROM1-related retinopathy from this study will contribute to the characterization of the natural history of disease and the exploration of the utility of several modalities to track progression and therefore to potentially be used in future interventional clinical trials.

Longitudinal Changes of Fixation Location and Stability Within 12 Months in Stargardt Disease: ProgStar Report No. 12.

PURPOSE: To investigate the natural history of Stargardt disease (STGD1) using fixation location and fixation stability. DESIGN: Multicenter, international, prospective cohort study. METHODS: Fixation testing was performed using the Nidek MP-1 microperimeter as part of the prospective, multicenter, natural history study on the Progression of Stargardt disease (ProgStar). A total of 238 patients with ABCA4-related STGD1 were enrolled at baseline (bilateral enrollment in 86.6%) and underwent repeat testing at months 6 and 12. RESULTS: Outcome measures included the distance of the preferred retinal locus from the fovea (PRL) and the bivariate contour ellipse area (BCEA). After 12 months of follow-up, the change in the eccentricity of the PRL from the anatomic fovea was -0.0014 degrees (95% confidence interval [CI], -0.27 degrees, 0.27 degrees; P = .99). The deterioration in the stability of fixation as expressed by a larger BCEA encompassing 1 standard deviation of all fixation points was 1.21 degrees squared (deg2) (95% CI, -1.23 deg2, 3.65 deg2; P = .33). Eyes with increases and decreases in PRL eccentricity and/or BCEA values were observed. CONCLUSIONS: Our observations point to the complexity of fixation parameters. The association of increasingly eccentric and unstable fixation with longer disease duration that is typically found in cross-sectional studies may be countered within individual patients by poorly understood processes like neuronal adaptation. Nevertheless, fixation parameters may serve as useful secondary outcome parameters in selected cases and for counseling patients to explain changes to their visual functionality.

Association of clinical headache features with stroke location: An MRI voxel-based symptom lesion mapping study.

Background We have recently shown that the presence of headache in ischemic stroke is associated with lesions of the insular cortex. The aim of this post-hoc subgroup analysis was to investigate the association of specific headache features with stroke location in patients with acute ischemic stroke. Methods In this observational study, patients (mean age: 61.5, 58% males) with ischemic stroke and acute headache (n = 49) were investigated. Infarcts were manually outlined on 3D diffusion weighted magnetic resonance imaging (MRI) scans and transformed into standard stereotaxic space; lesions of the left hemisphere were mirrored in the x-axis to allow a voxel-wise group analysis of all patients. We analyzed the association of lesion location and the following phenotypical characteristics by voxel-based symptom lesion mapping: Headache intensity, different qualities of headache (pulsating, tension-type like and stabbing), and the presence of nausea, of cranial autonomic symptoms and of light or noise sensitivity. Results Headache intensity was associated with lesions of the posterior insula, the operculum and the cerebellum. "Pulsating" headache occurred with widespread cortical and subcortical strokes. The presence of "tension-like" and "stabbing" headache was not related to specific lesion patterns. Nausea was associated with lesions in the posterior circulation territory. Cranial-autonomic symptoms were related to lesions of the parietal lobe, the somatosensory cortex (SI) and the middle temporal cortex. The presence of noise sensitivity was associated with cerebellar lesions, whereas light sensitivity was not related to specific lesions in our sample. Conclusion Headache phenotype in ischemic stroke appears to be related to specific ischemic lesion patterns.

Metrics and Acquisition Modes for Fixation Stability as a Visual Function Biomarker.

Purpose: To compare different metrics and acquisition modes of fixation stability as a new visual function biomarker in a large cohort of patients with ABCA4-related Stargardt disease from the multicenter prospective ProgStar study. Methods: Fixation was tested during a separate fixation exam and also dynamically during a sensitivity exam, using fundus-tracking microperimetry (Nidek MP-1). Fixation data were analyzed using the bivariate contour ellipse area (BCEA), the 2/4 degree method, and the Fujii classification. Results: In a total of 235 patients, the mean BCEA was larger when measured during the sensitivity exam (418 eyes; 12.5 vs. 4.6 deg2 during the fixation task in 427 eyes). Correlations between the two tests were generally weak. Fixation stability during the sensitivity test was significantly correlated with visual acuity. Comparing the BCEA values and the corresponding Fujii categories for these eyes revealed ranges of overlap where an eye with one defined BCEA value can fall into each of the three Fujii categories. Conclusions: Patients may have limited ability to fixate over defined time periods, which leads to significant differences between shorter and longer measurements of fixation stability. The most appropriate way to use this functional biomarker appears to be using continuous metrics for fixation stability, such as the BCEA, during a macular sensitivity test.

7-Hexagon Multifocal Electroretinography for an Objective Functional Assessment of the Macula in 14 Seconds.

PURPOSE: We present the multifocal electroretinogram (mfERG) with a 7-hexagon array as an objective test of macular function that can be recorded in 14 s. We provide normal values and investigate its reproducibility and validity. METHODS: Healthy participants underwent mfERG testing according to International Society for Clinical Electrophysiology of Vision (ISCEV) standards using the Espion Profile/D310 multifocal ERG system (Diagnosys, LLC, Lowell, MA, USA). One standard recording of a 61-hexagon array and 2 repeated recordings of a custom 7-hexagon array were obtained. RESULTS: A total of 13 subjects (mean age 46.9 years) were included. The median response densities were 12.5 nV/deg2 in the center and 5.2 nV/deg2 in the periphery. Intereye correlations were strong in both the center (ρCenter = 0.821; p < 0.0001) and the periphery (ρPeriphery = 0.862; p < 0.0001). Intraeye correlations were even stronger: ρCenter = 0.904 with p < 0.0001 and ρPeriphery = 0.955 with p < 0.0001. Bland-Altman plots demonstrated an acceptable retest mean difference in both the center and periphery, and narrow limits of agreement. We found strong correlations of the center (ρCenter = 0.826; p < 0.0001) and periphery (ρPeriphery = 0.848; p < 0.0001), with recordings obtained by the 61-hexagon method. CONCLUSIONS: The 7-hexagon mfERG provides reproducible results in agreement with results obtained according to the ISCEV standard.

Macular Sensitivity Measured With Microperimetry in Stargardt Disease in the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Study: Report No. 7.

Importance: New outcome measures for treatment trials for Stargardt disease type 1 (STGD1) and other macular diseases are needed. Microperimetry allows mapping of light sensitivity of the macula and provides topographic information on visual function beyond visual acuity. Objective: To measure and analyze retinal light sensitivity of the macula in STGD1 using fundus-controlled perimetry (microperimetry). Design, Setting, and Participants: This was a multicenter prospective cohort study. A total of 199 patients and 326 eyes with molecularly confirmed (ABCA4) STGD1 underwent testing with the Nidek MP-1 microperimeter as part of the multicenter, prospective Natural History of the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) study. Sensitivity of 68 retinal loci was tested, and the mean sensitivity (MS) was determined; each point was categorized as "normal," "relative," or "deep" scotoma. Main Outcomes and Measures: Mean sensitivity and the number of points with normal sensitivity, relative, or deep scotomas. Results: Mean (SD) patient age was 34.2 (14.7) years, mean (SD) best-corrected visual acuity of all eyes was 47.8 (16.9) Early Treatment Diabetic Retinopathy Study letter score (approximately 20/100 Snellen equivalent), and mean MS of all eyes of all 68 points was 11.0 (5.0) dB. The median number of normal points per eye was 49 (mean [SD], 41.3 [20.8]; range, 0-68); abnormal sensitivity and deep scotomas were more prevalent in the central macula. Mean sensitivity was lower in the fovea (mean [SD], 2.7 [4.4] dB) than in the inner (mean [SD], 6.8 [5.8] dB) and outer ring (mean [SD], 12.7 [5.3] dB). Overall MS per eye was 0.086 dB lower per year of additional age (95% CI, -0.13 to -0.041; P < .001) and 0.21 dB lower per additional year of duration of STGD1 (95% CI, -0.28 to -0.14; P < .001). Longer duration of STGD1 was associated with worse MS (ß = -0.18; P < .001), with a lower number of normal test points (ß = -0.71; P < .001), and with a higher number of deep scotoma points (ß = -0.70; P < .001). We found 11 eyes with low MS (<6 dB) but very good best-corrected visual acuity of at least 72 Early Treatment Diabetic Retinopathy Study letter score (20/40 Snellen equivalent). Conclusions and Relevance: We provide an extensive analysis of macular sensitivity parameters in STGD1 and demonstrate their association with demographic characteristics and vision. These data suggest microperimetry testing provides a more comprehensive assessment of retinal function and will be an important outcome measure in future clinical trials.