Ellipsoid Zone recovery in Macular Telangiectasia Type 2 (MacTel).

PURPOSE: To describe imaging features of Macular Telangiectasia Type 2 (MacTel) eyes experiencing ellipsoid zone (EZ) recovery. METHODS: MacTel patients with EZ-recovery were identified from the Natural History and Observational Registry Study and underwent retinal imaging including optical coherence tomography (OCT) and fundus photography. Eyes were graded according to the classification system by Gass and Blodi, the EZ-loss area was measured and OCT parameters were assessed by two independent readers. Parameters were analysed for their presence prior to EZ-recovery. RESULTS: Twenty-four eyes of 21 patients (12 female, 57.12%; mean age 68 ± 8.54 years) were included in this study and followed for 21.25 ± 12.79 months. At baseline, mean EZ-loss area was 0.036 ± 0.028 mm2 and 0.01 ± 0.013 mm2 at follow-up (p<0.001). A persisting external limiting membrane overlaying the EZ-loss was detected in 16 cases (66%) and hyperreflective changes in the outer retina were present in 18 cases (75%). Best corrected visual acuity was 0.23 (20/32) ± 0.33 logMar at baseline and 0.34 (20/40) ± 0.34 logMar at follow up (p=0.3). CONCLUSION: Distinct OCT features precede ellipsoid zone recovery in MacTel and warrant further studies investigating implications for patient care and clinical trial interpretation.

Initial experience with CytoSorb therapy in patients receiving left ventricular assist devices.

BACKGROUND: The use of left ventricular assist devices (LVAD) in patients with advance heart failure is still associated with an important risk of immune dysregulation and infections. The aim of this study was to determine whether extracorporeal blood purification using the CytoSorb device benefits patients after LVAD implantation in terms of complications and overall survival. MATERIALS AND METHODS: Between August 2010 and January 2020, 207 consecutive patients underwent LVAD implantation, of whom 72 underwent CytoSorb therapy and 135 did not. Overall survival, major adverse events, and laboratory parameters were compared between 112 propensity score-matched patients (CytoSorb: 72 patients; non-CytoSorb: 40 patients). RESULTS: WBC (p = .033), CRP (p = .001), and IL-6 (p < .001), significantly increased with LVAD implantation, while CytoSorb did not influence this response. In-hospital mortality and overall survival during follow-up were similar with CytoSorb. However, patients treated with CytoSorb were more likely to develop respiratory failure (54.2% vs. 30.0%, p = .024), need mechanical ventilation for longer than 6 days post-implant (50.0% vs. 27.5%, p = .035), and require tracheostomy during hospitalization (31.9% vs. 12.5%, p = .040). No other significant differences were observed with regard to major adverse events during follow-up. CONCLUSIONS: Overall, our results showed that CytoSorb might not convey a significant morbidity or mortality benefit for patients undergoing LVAD implantation.

Modeling of atrophy size trajectories: variable transformation, prediction and age-of-onset estimation.

BACKGROUND: To model the progression of geographic atrophy (GA) in patients with age-related macular degeneration (AMD) by building a suitable statistical regression model for GA size measurements obtained from fundus autofluorescence imaging. METHODS: Based on theoretical considerations, we develop a linear mixed-effects model for GA size progression that incorporates covariable-dependent enlargement rates as well as correlations between longitudinally collected GA size measurements. To capture nonlinear progression in a flexible way, we systematically assess Box-Cox transformations with different transformation parameters λ. Model evaluation is performed on data collected for two longitudinal, prospective multi-center cohort studies on GA size progression. RESULTS: A transformation parameter of λ=0.45 yielded the best model fit regarding the Akaike information criterion (AIC). When hypertension and hypercholesterolemia were included as risk factors in the model, they showed an association with progression of GA size. The mean estimated age-of-onset in this model was 67.21±6.49 years. CONCLUSIONS: We provide a comprehensive framework for modeling the course of uni- or bilateral GA size progression in longitudinal observational studies. Specifically, the model allows for age-of-onset estimation, identification of risk factors and prediction of future GA size. A square-root transformation of atrophy size is recommended before model fitting.

Outcomes of left ventricular assist device implantation for advanced heart failure in critically ill patients (INTERMACS 1 and 2): A retrospective study.

The use of left ventricular assist devices (LVADs) for advanced heart failure is becoming increasingly common. However, optimal timing and patient selection remain controversial. The aim of this study was to investigate outcomes of LVAD implantation for advanced heart failure in critically ill patients (INTERMACS 1 and 2). Between August 2010 and January 2020, 207 consecutive patients underwent LVAD implantation. Overall survival, major adverse events, and laboratory parameters were compared between patients in INTERMACS 1-2 (n = 107) and INTERMACS 3-5 (n = 100). Preoperative white blood cells, C-reactive protein, procalcitonin, bilirubin, alanine transaminase, and lactate dehydrogenase were all significantly higher in INTERMACS 1-2 when compared to INTERMACS 3-5 (P < .05). During hospitalization following LVAD implantation, patients in INTERMACS 1-2 were more likely to develop major infections (41.1% vs. 23.0%, P = .005), respiratory failure (57.9% vs. 25.0%, P < .001), mild (20.6% vs. 8.0%, P = .010), and moderate (31.8% vs. 7.0%, P < .001) right heart failure, and acute renal dysfunction (56.1% vs. 6.0%, P < .001). During a median follow-up of 2.00 years (interquartile range (IQR) 0.24-3.39 years), they had a higher incidence of thoracic (15.9% vs. 4.0%, P = .005) and gastrointestinal bleeding (21.5% vs. 11.0%, P = .042), as well as right heart failure (18.7% vs. 1%, P < .001). Risk of death was significantly higher in the INTERMACS 1-2 group (hazards ratio (HR) 1.64, 95% CI 1.12-2.40, P = .011). LVAD implantation in critically ill patients is associated with increased morbidity and mortality. Our results suggest that decision for LVAD should be not be delayed until INTERMACS 1 and 2 levels whenever possible.

The Impact of Obesity on Left Ventricular Assist Device Outcomes.

Background and Objectives: The understanding of high body mass index (BMI) and outcomes after Left Ventricular Assist Device (LVAD) implantation continues to evolve and the relationship has not been established yet. In this study, we investigated the effects of obesity (BMI > 30 kg/m2) on post-LVAD implantation outcomes. HeartWare LVAD and Heart Mate III LVAD were implanted. The primary outcome that was measured was mortality (in-hospital and on follow-up). The secondary outcomes that were measured were major adverse events. Materials and Methods: At our institution, the West German Heart and Vascular Center (Essen, Germany), from August 2010 to January 2020, a total of 210 patients received a long-term LVAD. Patients were stratified according to BMI ≥ 30 kg/m2 representing the obesity threshold. The first group (n = 162) had an average BMI of 24.2 kg/m2 (±2.9), and the second group (n = 48) had an average BMI of 33.9 kg/m2 (±3.2). Baseline demographics were analysed alongside comorbidities per group. Results: Overall mortality was not significantly different between the obese group (51.1% n = 24) and the nonobese group (55.2%, n = 85) (p = 0.619). The difference between the mean duration of survival of patients who expired after hospital discharge was insignificant (2.1 years ± 1.6, group 1; 2.6 years ± 1.5, group 2; p = 0.29). In-hospital mortality was unvaried between the two groups: group 1: n = 34 (44% out of overall group 1 deaths); group 2: n = 11 (45.8% out of overall group 2 deaths) (p > 0.05). Postoperative complications were unvaried between the obese and the non-obese group (all with p > 0.05). However, a significant difference was found with regards to follow-up neurological complications (18.5% vs. 37.8%, p = 0.01) and LVAD thrombosis (14.7% vs. 33.3%, p = 0.01), as both were higher in the obese population. Conclusion: Obesity does not form a barrier for LVAD implantation in terms of mortality (in-hospital and on follow up). However, a significantly higher incidence of follow-up LVAD thrombosis and neurological complications has been found in the obese group of patients.

PROGNOSTIC VALUE OF SHAPE-DESCRIPTIVE FACTORS FOR THE PROGRESSION OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To systematically compare the prognostic value of multiple shape-descriptive factors in the natural course of the disease. METHODS: A total of 296 eyes of 201 patients (female patients 130; mean age: 72.2 ± 13.08 years) with a median follow-up of 2.38 years from 2 prospective, noninterventional natural history studies (Fundus-Autofluorescence-in-Age-related-Macular-Degeneration [clinicaltrials.gov identifier NCT00393692], Directional-Spread-in-Geographic-Atrophy [NCT02051998]) were included in the analysis. Serial fundus autofluorescence images were annotated using semiautomated image analysis software to determine the lesion area, circularity, perimeter, and caliper diameters. These variables and the fundus autofluorescence phenotype were evaluated for prediction of the future square root progression rates using linear mixed-effects models. RESULTS: For the combined model, leave-one-out cross validation on patient level (Scenario 1: previously unknown patient) resulted in a goodness-to-fit (R value) of 0.244 and leave-one-out cross validation on visit level (Scenario 2: previous observation of the patient) in a R value of 0.391. This indicated that shape-descriptive factors could explain 24.4% of the variance in geographic atrophy progression in previously unknown patients and 39.1% in patients with previous observation. CONCLUSION: These findings confirm the relevance of shape-descriptive factors and previous progression as prognostic variables for geographic atrophy progression. However, a substantial part of the remaining variation in geographic atrophy progression seems to depend on other variables, some of which are visible in optical coherence tomography.

Association of Lesion Location and Functional Parameters with Vision-Related Quality of Life in Geographic Atrophy Secondary to Age-related Macular Degeneration.

OBJECTIVE: The primary goal of this study was to determine how structural and functional parameters influence the vision-related quality of life (VRQoL) in patients suffering from geographic atrophy (GA) secondary to age-related macular degeneration. DESIGN: This study was designed as a prospective, noninterventional, natural-history study (Directional Spread in Geographic-Atrophy study, NCT02051998). SUBJECTS: The research involved 82 patients with bilateral GA. METHODS: The study examined parameters including GA location as assessed by the ETDRS grid, best-corrected visual acuity, low-luminance visual acuity (LLVA), reading acuity, and speed. These parameters were then correlated with VRQoL, which was gauged using the National Eye Institute Visual Function Questionnaire 25. The analysis method employed was the least absolute shrinkage and selection operator with linear mixed-effects models. MAIN OUTCOME MEASURES: The central parameters measured in this study encompassed GA area, VRQoL scores associated with different GA subfields, and the significance of LLVA for foveal-sparing patients. RESULTS: On average, patients showed a total GA area of 2.9 ± 1.2 mm2 in the better eye (BE) and 3.1 ± 1.3 mm2 in the worse eye. The most significant associations with VRQoL scores for distance and near activities were observed in the inner lower and inner left subfields of the BE, respectively. For patients with foveal-sparing GA, the LLVA of the BE stood out as the most influential variable across all VRQoL scales. CONCLUSIONS: The study's findings point toward the pivotal role of GA location, especially the inner lower and inner left subfields of the BE, in relation to VRQoL in GA patients. The LLVA's importance becomes even more pronounced for foveal-sparing patients. These observations highlight the need for health care professionals to better understand the association between lesion location and patient-reported outcomes. This is critical for informing treatment decisions and refining the planning of interventional trials. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Outer Retinal Thickness Is Associated With Cognitive Function in Normal Aging to Intermediate Age-Related Macular Degeneration.

Purpose: Research on Alzheimer's disease (AD) and precursor states demonstrates a thinner retinal nerve fiber layer (NFL) compared to age-similar controls. Because AD and age-related macular degeneration (AMD) both impact older adults and share risk factors, we asked if retinal layer thicknesses, including NFL, are associated with cognition in AMD. Methods: Adults ≥ 70 years with normal retinal aging, early AMD, or intermediate AMD per Age-Related Eye Disease Study (AREDS) nine-step grading of color fundus photography were enrolled in a cross-sectional study. Optical coherence tomography (OCT) volumes underwent 11-line segmentation and adjustments by a trained operator. Evaluated thicknesses reflect the vertical organization of retinal neurons and two vascular watersheds: NFL, ganglion cell layer-inner plexiform layer complex (GCL-IPL), inner retina, outer retina (including retinal pigment epithelium-Bruch's membrane), and total retina. Thicknesses were area weighted to achieve mean thickness across the 6-mm-diameter Early Treatment of Diabetic Retinopathy Study (ETDRS) grid. Cognitive status was assessed by the National Institutes of Health Toolbox cognitive battery for fluid and crystallized cognition. Correlations estimated associations between cognition and thicknesses, adjusting for age. Results: Based on 63 subjects (21 per group), thinning of the outer retina was significantly correlated with lower cognition scores (P < 0.05). No other retinal thickness variables were associated with cognition. Conclusions: Only the outer retina (photoreceptors, supporting glia, retinal pigment epithelium, Bruch's membrane) is associated with cognition in aging to intermediate AMD; NFL was not associated with cognition, contrary to AD-associated condition reports. Early and intermediate AMD constitute a retinal disease whose earliest, primary impact is in the outer retina. Our findings hint at a unique impact on the brain from the outer retina in persons with AMD.

Acute and Long-Term Toxicity after Planned Intraoperative Boost and Whole Breast Irradiation in High-Risk Patients with Breast Cancer-Results from the Targeted Intraoperative Radiotherapy Boost Quality Registry (TARGIT BQR).

In the context of breast cancer treatment optimization, this study prospectively examines the feasibility and outcomes of utilizing intraoperative radiotherapy (IORT) as a boost in combination with standard external beam radiotherapy (EBRT) for high-risk patients. Different guidelines recommend such a tumor bed boost in addition to whole breast irradiation with EBRT for patients with risk factors for local breast cancer recurrence. The TARGIT BQR (NCT01440010) is a prospective, multicenter registry study aimed at ensuring the quality of clinical outcomes. It provides, for the first time, data from a large cohort with a detailed assessment of acute and long-term toxicity following an IORT boost using low-energy X-rays. Inclusion criteria encompassed tumors up to 3.5 cm in size and preoperative indications for a boost. The IORT boost, administered immediately after tumor resection, delivered a single dose of 20 Gy. EBRT and systemic therapy adhered to local tumor board recommendations. Follow-up for toxicity assessment (LENT SOMA criteria: fibrosis, teleangiectasia, retraction, pain, breast edema, lymphedema, hyperpigmentation, ulceration) took place before surgery, 6 weeks to 90 days after EBRT, 6 months after IORT, and then annually using standardized case report forms (CRFs). Between 2011 and 2020, 1133 patients from 10 centers were preoperatively enrolled. The planned IORT boost was conducted in 90%, and EBRT in 97% of cases. Median follow-up was 32 months (range 1-120, 20.4% dropped out), with a median age of 61 years (range 30-90). No acute grade 3 or 4 toxicities were observed. Acute side effects included erythema grade 1 or 2 in 4.4%, palpable seroma in 9.1%, punctured seroma in 0.3%, and wound healing disorders in 2.1%. Overall, chronic teleangiectasia of any grade occurred in 16.2%, fibrosis grade ≥ 2 in 14.3%, pain grade ≥ 2 in 3.4%, and hyperpigmentation in 1.1%. In conclusion, a tumor bed boost through IORT using low-energy X-rays is a swift and feasible method that demonstrates low rates in terms of acute or long-term toxicity profiles in combination with whole breast irradiation.

Human selection bias drives the linear nature of the more ground truth effect in explainable deep learning optical coherence tomography image segmentation.

Supervised deep learning (DL) algorithms are highly dependent on training data for which human graders are assigned, for example, for optical coherence tomography (OCT) image annotation. Despite the tremendous success of DL, due to human judgment, these ground truth labels can be inaccurate and/or ambiguous and cause a human selection bias. We therefore investigated the impact of the size of the ground truth and variable numbers of graders on the predictive performance of the same DL architecture and repeated each experiment three times. The largest training dataset delivered a prediction performance close to that of human experts. All DL systems utilized were highly consistent. Nevertheless, the DL under-performers could not achieve any further autonomous improvement even after repeated training. Furthermore, a quantifiable linear relationship between ground truth ambiguity and the beneficial effect of having a larger amount of ground truth data was detected and marked as the more-ground-truth effect.

Longitudinal cosmetic outcome after planned IORT boost with low kV X-rays-monocentric results from the TARGIT BQR registry.

Background: Intraoperative radiotherapy can serve as an anticipated boost (IORT boost) in combination with a subsequent external whole breast irradiation in high-risk breast cancer patients and is part of many guidelines. Nevertheless, there are only few prospective data available regarding cosmetic outcome after IORT boost using kV X-rays. The aim of this study was to evaluate the cosmetic outcome of patients treated within the prospective phase IV TARGeted Intraoperative radioTherapy (TARGIT) Boost Quality Registry (BQR) study (NCT01440010) in one center. Methods: In the context of the TARGIT BQR study standardized photos in three positions (arms down, arms up, from the side) were available for different time points. For this analysis a layperson, a radiation oncologist and a gynecologist evaluated available photos at different time points during follow-up with up to 4 years using the Harvard scale (comparison of treated and the untreated breast; rating: excellent, good, fair, poor). Longitudinal results were compared to preoperative results (baseline). Results: Seventy-three patients were available for the analysis. Baseline cosmetic assessment was excellent/good in 98.8% (mean value for all three positions). Postoperative cosmetic outcome (median) was good for all positions and remained constant for 4 years. Around 30% of the patients showed a constant or even improved cosmetic outcome compared to baseline. Only few patients showed a poor result at 4 years. The majority of patients showed an excellent or good cosmetic outcome at all time points. Conclusions: Patients from the prospective TARGIT BQR study treated with IORT boost and additional whole breast irradiation showed good or excellent cosmetic outcomes in most cases during 4 years of follow-up. These results add important information for shared decision making in breast cancer patients.

Impact of lesion location and functional parameters on vision-related quality of life in geographic atrophy secondary to AMD.

Background/Aims: The primary objective was to determine how structural and functional parameters influence the vision-related quality of life (VRQoL) in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Methods: This prospective, non-interventional, natural-history 'Directional Spread in Geographic-Atrophy' study was conducted at the University Eye Hospital in Bonn, enrolling 82 patients with bilateral GA. Parameters such as GA location (assessed by the Early Treatment Diabetic Retinopathy Study grid), best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), reading acuity, and speed were examined. The association between these parameters and VRQoL, as gauged using the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25), was analyzed through least absolute shrinkage and selection operator with linear mixed-effects models. Results: The average total GA area observed was 2.9 ± 1.2 mm2 (better eye) and 3.1 ± 1.3 mm2 (worse eye). The VRQoL scores for distance and near activities were most associated with the inner lower and inner left subfields of the better eye. For foveal-sparing patients, the LLVA of the better eye was the predominant determinate impacting all VRQoL scales. Conclusion: GA location, specifically the inner lower and inner left subfields of the better eye, has a notable effect on VRQoL in GA patients. LLVA stands out as especially vital in foveal-sparing patients, underscoring the importance for clinicians to incorporate considerations of GA location and functional parameters into their risk-benefit assessments for emerging treatments.

Relative Ellipsoid Zone Reflectivity in Macular Telangiectasia Type 2.

Purpose: The relative ellipsoid zone reflectivity (rEZR) has been proposed as an innovative biomarker for photoreceptor integrity. This study evaluates the rEZR in macular telangiectasia type 2 (MacTel) eyes of different disease stages. Methods: The mean rEZR (ratio ellipsoid zone [EZ]/external limiting membrane [ELM] reflectivity [arbitrary units {AUs}], grey level range = 0-1) was analyzed for an entire spectral domain optical coherence tomography volume scan (global) and for each subfield of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid (topographic) in patients with MacTel and controls. MacTel disease severity was classified according to Gass and Blodi. Results: Linear mixed-model analysis of 145 eyes of 74 patients and 50 eyes of 25 controls revealed globally lower, yet not statistically significant, rEZR values in MacTel eyes. Topographically, most pronounced decreases were found in stages 3 and 4/5 for the temporal inner (coefficient estimates [CEs] = -25.4 [-38.2; -12.6] and -34.1 [-48.7; -19.6] AU, both: P < 0.001), the inferior inner (-29.9 [-44.6; -15.6] and -35.3 [-52.1; -18.5] AU, both: P < 0.001), the nasal inner (-21.5 [-35.52; -7.4] and -31.6 [-47.6; -15.6] AU, P = 0,003 and P < 0.001), and in the superior inner subfield of stage 4/5 (-25.0 [-42.0; -7.9] AU, P = 0.004). Conclusions: The rEZR showed association with disease severity and the predilection area of MacTel. Given the current understanding of the pathophysiological concept of MacTel, these findings underscore the value of the rEZR as a potential novel biomarker for outer retinal integrity. Longitudinal studies are demanded to better characterize its value as a biomarker for early photoreceptor alterations and disease progression in MacTel.

Characteristics and Spatial Distribution of Structural Features in Age-Related Macular Degeneration: A MACUSTAR Study Report.

PURPOSE: To report the prevalence and topographic distribution of structural characteristics in study participants with age-related macular degeneration (AMD) and controls in the cross-sectional study part of the MACUSTAR study (ClinicalTrials.gov Identifier: NCT03349801). DESIGN: European, multicenter cohort study. SUBJECTS: Overall, 301 eyes of 301 subjects with early (n = 34), intermediate (n = 168), and late AMD (n = 43), as well as eyes without any AMD features (n = 56). METHODS: In study eyes with intermediate AMD (iAMD), the presence of structural AMD biomarkers, including pigmentary abnormalities (PAs), pigment epithelium detachment (PED), refractile deposits, reticular pseudodrusen (RPD), hyperreflective foci (HRF), incomplete/complete retinal pigment epithelium (RPE), and outer retinal atrophy (i/cRORA), and quiescent choroidal neovascularization (qCNV) was systematically determined in the prospectively acquired multimodal retinal imaging cross-sectional data set of MACUSTAR. Retinal layer thicknesses and the RPE drusen complex (RPEDC) volume were determined for the total study cohort in spectral-domain (SD) OCT imaging using a deep-learning-based algorithm. MAIN OUTCOME MEASURES: Prevalence and topographic distribution of structural iAMD features. RESULTS: A total of 301 study eyes of 301 subjects with a mean (± standard deviation) age of 71.2 ± 7.20 years (63.1% women) were included. Besides large drusen, the most prevalent structural feature in iAMD study eyes were PA (57.1%), followed by HRF (51.8%) and RPD (22.0%). Pigment epithelium detachment lesions were observed in 4.8%, vitelliform lesions in 4.2%, refractile deposits in 3.0%, and qCNV in 2.4%. Direct precursor lesions for manifest retinal atrophy were detected in 10.7% (iRORA) and 4.2% (cRORA) in iAMD eyes. Overall, the highest RPEDC volume with a median of 98.92 × 10-4 mm³ was found in iAMD study eyes. Spatial analysis demonstrated a predominant distribution of RPD in the superior and temporal subfields at a foveal eccentricity of 1.5 to 2 mm, whereas HRF and large drusen had a distinct topographic distribution involving the foveal center. CONCLUSIONS: Detailed knowledge of the prevalence and distribution of structural iAMD biomarkers is vital to identify reliable outcome measure for disease progression. Longitudinal analyses are needed to evaluate their prognostic value for conversion to advanced disease stages. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Comparing Fluorescence Lifetime Imaging Ophthalmoscopy in Atrophic Areas of Retinal Diseases.

Purpose: Fluorescence lifetime imaging ophthalmoscopy (FLIO) is a non-invasive imaging modality to investigate the human retina. This study compares FLIO lifetimes in different degenerative retinal diseases. Methods: Included were eyes with retinal pigment epithelium (RPE) and/or photoreceptor atrophy due to Stargardt disease (n = 66), pattern dystrophy (n = 18), macular telangiectasia type 2 (n = 49), retinitis pigmentosa (n = 28), choroideremia (n = 26), and geographic atrophy (n = 32) in age-related macular degeneration, as well as 37 eyes of 37 age-matched healthy controls. Subjects received Heidelberg Engineering FLIO, autofluorescence intensity, and optical coherence tomography imaging. Amplitude-weighted mean FLIO lifetimes (τm) were calculated and analyzed. Results: Retinal FLIO lifetimes show significant differences depending on the disease. Atrophic areas in geographic atrophy and choroideremia showed longest mean FLIO lifetimes. τm values within areas of RPE and outer nuclear layer atrophy were significantly longer than within areas with preserved outer nuclear layer (P < 0.001) or non-atrophic areas (P < 0.001). Conclusions: FLIO is able to contribute additional information regarding differences in chronic degenerative retinal diseases. Although it cannot replace conventional autofluorescence imaging, FLIO adds to the knowledge in these diseases and may help with the correct differentiation between them. This may lead to a more in-depth understanding of the pathomechanisms related to atrophy and types of progression. Translational Relevance: Differences between atrophic retinal diseases highlighted by FLIO may indicate separate pathomechanisms leading to atrophy and disease progression.

Association of Reading Performance in Geographic Atrophy Secondary to Age-Related Macular Degeneration With Visual Function and Structural Biomarkers.

IMPORTANCE: As a disabling and frequent disease, geographic atrophy secondary to age-related macular degeneration (AMD) constitutes an important study subject. Emerging clinical trials require suitable end points. The characterization and validation of reading performance as a functional outcome parameter is warranted. OBJECTIVE: To prospectively evaluate reading performance in geographic atrophy and to assess its association with established visual function assessments and structural biomarkers. DESIGN, SETTING, AND PARTICIPANTS: The noninterventional, prospective natural history Directional Spread in Geographic Atrophy study included patients with geographic atrophy secondary to AMD who were recruited at the University Hospital in Bonn, Germany. Participants were enrolled from June 2013 to June 2016. Analysis began December 2019 and ended January 2021. MAIN OUTCOMES AND MEASURES: Reading acuity and reading speed were assessed using Radner charts. Longitudinal fundus autofluorescence and infrared reflectance images were semiautomatically annotated for geographic atrophy, followed by extraction of shape-descriptive variables. Linear mixed-effects models were applied to investigate the association of those variables with reading performance. RESULTS: A total of 150 eyes of 85 participants were included in this study (median [IQR] age, 77.9 [72.4-82.1] years; 51 women [60%]; 34 men [40%]). Reading performance was impaired with a median (IQR) monocular reading acuity of 0.9 (0.4-1.3) logarithm of the reading acuity determination and a reading speed of 52.8 (0-123) words per minute. In the multivariable cross-sectional analysis, best-corrected visual acuity, area of geographic atrophy in the central Early Treatment Diabetic Retinopathy Study (ETDRS) subfield, classification of noncenter vs center-involving geographic atrophy, and area of geographic atrophy in the inner-right ETDRS subfield showed strongest associations with reading acuity (cross-validated R2for reading acuity = 0.69). Regarding reading speed, the most relevant variables were best-corrected visual acuity, low-luminance visual acuity, area of geographic atrophy in the central ETDRS subfield, in the inner-right ETDRS subfield, and in the inner-upper ETDRS subfield (R2 for reading speed = 0.67). In the longitudinal analysis, a similar prediction accuracy for reading performance was determined (R2 for reading acuity = 0.73; R2 for reading speed = 0.70). Prediction accuracy did not improve when follow-up time was added as an independent variable. Binocular reading performance did not differ from reading performance in the better-seeing eye. CONCLUSIONS AND RELEVANCE: The association of reading acuity and speed with visual functional and structural biomarkers supports the validity of reading performance as a meaningful end point in clinical trials. These findings suggest that measures in clinical and low-vision care for patients with geographic atrophy should focus primarily on the better-seeing eye.

Determinants of Quality of Life in Geographic Atrophy Secondary to Age-Related Macular Degeneration.

Purpose: To longitudinally evaluate vision-related quality of life (VRQoL) in geographic atrophy (GA) secondary to age-related macular degeneration (AMD) and define its relation to visual function and structural biomarkers. Methods: Patients with GA secondary to AMD were recruited in the context of the prospective, non-interventional, natural-history Directional Spread in Geographic-Atrophy study (NCT02051998). Fundus autofluorescence and infrared reflectance images were semi-automatically annotated for GA. Linear mixed-effects models were applied to investigate the association of putative determinants with the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) VRQoL. Results: A total of 87 patients with a mean age ± SD of 77.07 ± 7.49 years were included in the analysis. At baseline, median (IQR) best-corrected visual acuity (BCVA) was 0.3 (0.51) for the better eye and 0.89 (0.76) for the worse eye; 46% of the patients showed binocular and 25.3% monocular non-central GA. The VRQoL composite score was impaired: 69.96 (24.03). Sixty-six patients with a median of 2 (2) follow-up visits after 1.08 (0.78) years were examined longitudinally. Conclusions: Vision-related quality of life is significantly impaired in patients with GA secondary to AMD. The cross-sectional and longitudinal association of VRQoL with visual functional and structural biomarkers supports the validity of the NEI VFQ-25 VRQoL.

Determinants of Reading Performance in Eyes with Foveal-Sparing Geographic Atrophy.

PURPOSE: To identify anatomic determinants of reading performance in eyes with foveal-sparing geographic atrophy (GA). DESIGN: Prospectively recruited, cross-sectional study, SIGHT (clinicaltrials.gov identifier, NCT02332343). PARTICIPANTS: Patients with foveal-sparing GA secondary to age-related macular degeneration (AMD). METHODS: Monocular best-corrected visual acuity and reading acuity together with reading speed were assessed using Radner charts. Fundus autofluorescence, near-infrared reflectance, and spectral-domain OCT images were acquired using a Spectralis device. The minimal required reading rectangle (M3R), 19 letters × 2.4 lines in the smallest readable print size of an individual eye, was computed. The status of the M3R was determined as either free of atrophy or involved in the atrophic process, and the impact on reading was assessed. MAIN OUTCOME MEASURES: Radner reading score (logRAD) and reading speed (words per minute [wpm]). RESULTS: A total of 45 eyes of 31 patients (30 women; mean age, 76.14 years [range, 64.17-89.22 years]) were included. Median best-corrected visual acuity was 0.20 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/32). Reading score was 0.52 logRAD (IQR, 0.30-1.4 logRAD) and maximum reading speed was 141.19 wpm (IQR, 105.52-164.62 wpm). In 27 eyes, the M3R was involved in the atrophic process. This was associated with a significant worsening in Radner score (1.21 logRAD [IQR, 0.46-1.40 logRAD] vs. 0.31 logRAD [IQR, 0.20-0.51 logRAD]; P < 0.001) and reading speed (110.84 wpm [IQR, 90.0-131.92 wpm] vs. 162.34 wpm [IQR, 137.51-176.66 wpm]; P = 0.002). Eyes in which the M3R was nonatrophic additionally showed an increase in reading speed with decreasing print size (peak increase, +73.08 wpm [IQR, 27.43-86.64 wpm] compared with the largest test sentence). CONCLUSIONS: The results indicate that a defined area on the retina that can be assessed by retinal imaging is required for unhindered reading in patients with foveal-sparing GA. The findings highlight that smaller test sentences can be read faster by patients with this AMD subphenotype. Our results allow prediction of reading impairment based on imaging parameters in clinical routine and may support establishing anatomic surrogate end points in clinical trials. Furthermore, the findings could be used to facilitate the adjustment of magnifying reading aids.