Retinal sensitivity in macular subfields and their association with contrast sensitivity in early and intermediate age-related macular degeneration.

Purpose To evaluate retinal sensitivity in subfields and its association with the novel quick contrast sensitivity function (qCSF) in patients with early age-related macular degeneration (eAMD), in patients with intermediate AMD (iAMD), and in healthy controls. Methods In this prospective longitudinal study retinal sensitivity of a customized 24-point grid was assessed by microperimetry Macular Integrity Assessment (MAIA, CenterVue, Padova, Italy) and divided into different subfields. The Multiple Contrast Vision Meter (Adaptive Sensory Technology, San Diego, CA) was used for qCSF testing. Linear models were used to test the association of functional metrics with variables of interest. Results 92 study eyes from 92 participants were analyzed (13 eAMD, 31 iAMD, and 48 controls). Microperimetry subfield comparison showed significant differences (p<0.0001) in the control group between superior and inferior hemifield as well as between central and peripheral subfields. For eAMD significant differences were found between central and peripheral subfields (p<0.001) and specific subfields (p<0.05) and finally for iAMD between specific quadrants (p<0.05) and specific squares (p<0.05). Significant associations of retinal sensitivity with qCSF metrics were found for the area underneath the logarithmic contrast sensitivity function (AULCSF), contrast acuity (CA) and for the contrast sensitivity at specific spatial frequencies. Conclusions This study showed significant differences in the evaluated retinal sensitivity subfields providing localized natural history data for retinal sensitivity in healthy controls, and patients with eAMD and iAMD.

Systematic review of prognostic factors associated with progression to late age-related macular degeneration: Pinnacle study report 2.

There is a need to identify accurately prognostic factors that determine the progression of intermediate to late-stage age-related macular degeneration (AMD). Currently, clinicians cannot provide individualised prognoses of disease progression. Moreover, enriching clinical trials with rapid progressors may facilitate delivery of shorter intervention trials aimed at delaying or preventing progression to late AMD. Thus, we performed a systematic review to outline and assess the accuracy of reporting prognostic factors for the progression of intermediate to late AMD. A meta-analysis was originally planned. Synonyms of AMD and disease progression were used to search Medline and EMBASE for articles investigating AMD progression published between 1991 and 2021. Initial search results included 3229 articles. Predetermined eligibility criteria were employed to systematically screen papers by two reviewers working independently and in duplicate. Quality appraisal and data extraction were performed by a team of reviewers. Only 6 studies met the eligibility criteria. Based on these articles, exploratory prognostic factors for progression of intermediate to late AMD included phenotypic features (e.g. location and size of drusen), age, smoking status, ocular and systemic co-morbidities, race, and genotype. Overall, study heterogeneity precluded reporting by forest plots and meta-analysis. The most commonly reported prognostic factors were baseline drusen volume/size, which was associated with progression to neovascular AMD, and outer retinal thinning linked to progression to geographic atrophy. In conclusion, poor methodological quality of included studies warrants cautious interpretation of our findings. Rigorous studies are warranted to provide robust evidence in the future.

Evaluating Contrast Sensitivity in Early and Intermediate Age-Related Macular Degeneration With the Quick Contrast Sensitivity Function.

Purpose: The purpose of this study was to describe, validate, and compare the contrast sensitivity functions (CSFs) acquired with the novel quick CSF (qCSF) method from patients with early and intermediate age-related macular degeneration (eAMD and iAMD) and healthy controls. Methods: This is a cross-sectional analysis of contrast sensitivity (CS) and visual acuity (VA) baseline data from the prospective Multimodal Functional and Structural Visual System Characterization (MUMOVI) study. The qCSF testing was conducted with the manifold contrast vision meter (Adaptive Sensory Technology, San Diego, CA, USA). CS levels at spatial frequencies from 1 cycle per degree (CPD) to 18 CPD, the area underneath the logarithmic contrast sensitivity function (AULCSF), and contrast acuity (CA) were analyzed. The association of functional metrics with variables of interest was tested with linear models. Results: Ninety-four study eyes from 94 study patients were included in the analysis (13 patients with eAMD, 33 patients with iAMD, and 48 healthy controls). Significant differences between the eAMD and the iAMD model estimates were only found for CS at 1 CPD (t value = -2.9, P value = 0.006) and CS at 1.5 CPD (-2.7, 0.01). A specific association between smoking years and CS at 1 CPD (P = 0.02) and CS at 1.5 CPD (P = 0.03) could be described in patients with AMD. Conclusions: The qCSF testing allows the fast measurement of the whole CSF, enabling the integration into clinical routine. We showed that novel qCSF-derived metrics detect slight functional differences between AMD stages, which testing by Pelli-Robson charts or VA testing would miss. This study, therefore, yields novel qCSF-derived candidate metrics for therapeutic trials in AMD.

Comparison of Novel Volumetric Microperimetry Metrics in Intermediate Age-Related Macular Degeneration: PINNACLE Study Report 3.

Purpose: To investigate and compare novel volumetric microperimetry (MP)-derived metrics in intermediate age-related macular degeneration (iAMD), as current MP metrics show high variability and low sensitivity. Methods: This is a cross-sectional analysis of microperimetry baseline data from the multicenter, prospective PINNACLE study (ClinicalTrials.gov NCT04269304). The Visual Field Modeling and Analysis (VFMA) software and an open-source implementation (OSI) were applied to calculate MP-derived hill-of-vison (HOV) surface plots and the total volume (VTOT) beneath the plots. Bland-Altman plots were used for methodologic comparison, and the association of retinal sensitivity metrics with explanatory variables was tested with mixed-effects models. Results: In total, 247 eyes of 189 participants (75 ± 7.3 years) were included in the analysis. The VTOT output of VFMA and OSI exhibited a significant difference (P < 0.0001). VFMA yielded slightly higher coefficients of determination than OSI and mean sensitivity (MS) in univariable and multivariable modeling, for example, in association with low-luminance visual acuity (LLVA) (marginal R2/conditional R2: VFMA 0.171/0.771, OSI 0.162/0.765, MS 0.133/0.755). In the multivariable analysis, LLVA was the only demonstrable predictor of VFMA VTOT (t-value, P-value: -7.5, <0.001) and MS (-6.5, <0.001). Conclusions: The HOV-derived metric of VTOT exhibits favorable characteristics compared to MS in evaluating retinal sensitivity. The output of VFMA and OSI is not exactly interchangeable in this cross-sectional analysis. Longitudinal analysis is necessary to assess their performance in ability-to-detect change. Translational Relevance: This study explores new volumetric MP endpoints for future application in therapeutic trials in iAMD and reports specific characteristics of the available HOV software applications.

Exploring Healthy Retinal Aging with Deep Learning.

Purpose: To study the individual course of retinal changes caused by healthy aging using deep learning. Design: Retrospective analysis of a large data set of retinal OCT images. Participants: A total of 85 709 adults between the age of 40 and 75 years of whom OCT images were acquired in the scope of the UK Biobank population study. Methods: We created a counterfactual generative adversarial network (GAN), a type of neural network that learns from cross-sectional, retrospective data. It then synthesizes high-resolution counterfactual OCT images and longitudinal time series. These counterfactuals allow visualization and analysis of hypothetical scenarios in which certain characteristics of the imaged subject, such as age or sex, are altered, whereas other attributes, crucially the subject's identity and image acquisition settings, remain fixed. Main Outcome Measures: Using our counterfactual GAN, we investigated subject-specific changes in the retinal layer structure as a function of age and sex. In particular, we measured changes in the retinal nerve fiber layer (RNFL), combined ganglion cell layer plus inner plexiform layer (GCIPL), inner nuclear layer to the inner boundary of the retinal pigment epithelium (INL-RPE), and retinal pigment epithelium (RPE). Results: Our counterfactual GAN is able to smoothly visualize the individual course of retinal aging. Across all counterfactual images, the RNFL, GCIPL, INL-RPE, and RPE changed by -0.1 µm ± 0.1 µm, -0.5 µm ± 0.2 µm, -0.2 µm ± 0.1 µm, and 0.1 µm ± 0.1 µm, respectively, per decade of age. These results agree well with previous studies based on the same cohort from the UK Biobank population study. Beyond population-wide average measures, our counterfactual GAN allows us to explore whether the retinal layers of a given eye will increase in thickness, decrease in thickness, or stagnate as a subject ages. Conclusion: This study demonstrates how counterfactual GANs can aid research into retinal aging by generating high-resolution, high-fidelity OCT images, and longitudinal time series. Ultimately, we envision that they will enable clinical experts to derive and explore hypotheses for potential imaging biomarkers for healthy and pathologic aging that can be refined and tested in prospective clinical trials. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Developing and validating a multivariable prediction model which predicts progression of intermediate to late age-related macular degeneration-the PINNACLE trial protocol.

AIMS: Age-related macular degeneration (AMD) is characterised by a progressive loss of central vision. Intermediate AMD is a risk factor for progression to advanced stages categorised as geographic atrophy (GA) and neovascular AMD. However, rates of progression to advanced stages vary between individuals. Recent advances in imaging and computing technologies have enabled deep phenotyping of intermediate AMD. The aim of this project is to utilise machine learning (ML) and advanced statistical modelling as an innovative approach to discover novel features and accurately quantify markers of pathological retinal ageing that can individualise progression to advanced AMD. METHODS: The PINNACLE study consists of both retrospective and prospective parts. In the retrospective part, more than 400,000 optical coherent tomography (OCT) images collected from four University Teaching Hospitals and the UK Biobank Population Study are being pooled, centrally stored and pre-processed. With this large dataset featuring eyes with AMD at various stages and healthy controls, we aim to identify imaging biomarkers for disease progression for intermediate AMD via supervised and unsupervised ML. The prospective study part will firstly characterise the progression of intermediate AMD in patients followed between one and three years; secondly, it will validate the utility of biomarkers identified in the retrospective cohort as predictors of progression towards late AMD. Patients aged 55-90 years old with intermediate AMD in at least one eye will be recruited across multiple sites in UK, Austria and Switzerland for visual function tests, multimodal retinal imaging and genotyping. Imaging will be repeated every four months to identify early focal signs of deterioration on spectral-domain optical coherence tomography (OCT) by human graders. A focal event triggers more frequent follow-up with visual function and imaging tests. The primary outcome is the sensitivity and specificity of the OCT imaging biomarkers. Secondary outcomes include sensitivity and specificity of novel multimodal imaging characteristics at predicting disease progression, ROC curves, time from development of imaging change to development of these endpoints, structure-function correlations, structure-genotype correlation and predictive risk models. CONCLUSIONS: This is one of the first studies in intermediate AMD to combine both ML, retrospective and prospective AMD patient data with the goal of identifying biomarkers of progression and to report the natural history of progression of intermediate AMD with multimodal retinal imaging.

Lateral Geniculate Nucleus Volume Determined on MRI Correlates With Corresponding Ganglion Cell Layer Loss in Acquired Human Postgeniculate Lesions.

Purpose: To quantitatively assess lateral geniculate nucleus (LGN) volume loss in the presence of lesions in the postgeniculate pathway and its correlation with optical coherence tomography retinal parameters. Methods: This was a case control study of patients recruited at the University Hospital Zurich, Switzerland. Nine patients who were suffering from lesions in the postgeniculate pathway acquired at least 3 months earlier participated. Retinal parameters were analyzed using spectral domain optical coherence tomography and a newly developed magnetic resonance imaging protocol with improved contrast to noise ratio was applied to measure LGN volume. Results: The affected LGN volume in the patients (mean volume 73.89 ± 39.08 mm3) was significantly smaller compared with the contralateral unaffected LGN (mean volume 131.43 ± 12.75 mm3), as well as compared with healthy controls (mean volume 107 ± 24.4 mm3). Additionally, the ganglion cell layer thickness corresponding with the affected versus unaffected side within the patient group differed significantly (mean thickness 40.5 ± 4.11 µm vs 45.7 ± 4.79 µm) compared with other retinal parameters. A significant linear correlation could also be shown between relative LGN volume loss and ganglion cell layer thickness decrease. Conclusions: Corresponding LGN volume reduction could be shown in patients with postgeniculate lesions using a newly developed magnetic resonance imaging protocol. LGN volume decrease correlated with ganglion cell layer thickness reduction as a sign of trans-synaptic retrograde neuronal degeneration.

Widespread White Matter Alterations in Patients With Visual Snow Syndrome.

Background: Visual snow is considered a disorder of central visual processing resulting in a perturbed perception of constant binocular flickering or pixilation of the whole visual field. The underlying neurophysiological and structural alterations remain elusive. Methods: In this study, we included patients (final n = 14, five dropouts; five females, mean age: 32 years) with visual snow syndrome (VSS) and age- and sex-matched controls (final n = 20, 6 dropouts, 13 females, mean age: 28.2 years). We applied diffusion tensor imaging to examine possible white matter (WM) alterations in patients with VSS. Results: The patient group demonstrated higher (p-corrected < 0.05, adjusted for age and sex) fractional anisotropy (FA) and lower mean diffusivity (MD) and radial diffusivity (RD) compared to controls. These changes were seen in the prefrontal WM (including the inferior fronto-occipital fascicle), temporal and occipital WM, superior and middle longitudinal fascicle, and sagittal stratum. When additionally corrected for migraine or tinnitus-dominant comorbidities in VSS-similar group differences were seen for FA and RD, but less pronounced. Conclusions: Our results indicate that patients with VSS present WM alterations in parts of the visual cortex and outside the visual cortex. As parts of the inferior fronto-occipital fascicle and sagittal stratum are associated with visual processing and visual conceptualisation, our results suggest that the WM alterations in these regions may indicate atypical visual processing in patients with VSS. Yet, the frequent presence of migraine and other comorbidities such as tinnitus in VSS makes it difficult to attribute WM disruptions solely to VSS.

Cyclotorsion Measurement on Scanning Laser Ophthalmoscopy Imaging Compared With Fundus Photography in Patients With Fourth Nerve Palsy and Healthy Controls: CySLO-IV Study.

BACKGROUND: The purpose of the study is to evaluate the agreement of the foveopapillary angle (FPA) on conventional fundus photography (c-FPA) with the FPA on scanning laser ophthalmoscopy (SLO) imaging (SLO-FPA) in patients with fourth nerve palsy and healthy controls (HCs). METHODS: The FPA was measured in both eyes of 25 patients and 25 HCs in synedra View (c-FPA) and with the integrated algorithm of the Heidelberg Spectralis OCT (SLO-FPA). The primary endpoint was the agreement of both measurements. Furthermore, we evaluated the influence of the eye tracker, the influence of fixation on objective torsion, and the FPA cutoff between patients and HCs. RESULTS: The mean SLO-FPA in patients (6/25 acquired palsies) was 11.3 ± 3.6° and 6.4 ± 2.1° in HCs. The mean c-FPA was 11.4 ± 4.0° and 5.8 ± 2.2°, respectively. The Bland-Altman plot of c-FPA vs SLO-FPA in patients and HCs shows no systematic bias (mean of -0.28°). Limits of agreement were -6.58 and 6.02°. Using the eye tracker had no systematic effect. There was no evidence for an immediate shift of torsion with change of fixation (24/25 patients and 23/25 HCs). Discrimination between patients and HCs by the SLO-FPA is very good with an area under the curve = 0.92 (95% confidence interval: 0.84-0.99). CONCLUSIONS: SLO-FPA measurement allows convenient and consistent assessment of objective cyclotorsion. There was no systematic bias in the difference between SLO-FPA and traditional c-FPA; thus, SLO-FPA is a valuable alternative to the commonly used c-FPA. Using the eye tracker is recommended for proper centering of the ring scan.

Abnormal Connectivity and Brain Structure in Patients With Visual Snow.

OBJECTIVE: Visual snow (VS) is a distressing, life-impacting condition with persistent visual phenomena. VS patients show cerebral hypermetabolism within the visual cortex, resulting in altered neuronal excitability. We hypothesized to see disease-dependent alterations in functional connectivity and gray matter volume (GMV) in regions associated with visual perception. METHODS: Nineteen patients with VS and 16 sex- and age-matched controls were recruited. Functional magnetic resonance imaging (fMRI) was applied to examine resting-state functional connectivity (rsFC). Volume changes were assessed by means of voxel-based morphometry (VBM). Finally, we assessed associations between MRI indices and clinical parameters. RESULTS: Patients with VS showed hyperconnectivity between extrastriate visual and inferior temporal brain regions and also between prefrontal and parietal (angular cortex) brain regions (p < 0.05, corrected for age and migraine occurrence). In addition, patients showed increased GMV in the right lingual gyrus (p < 0.05 corrected). Symptom duration positively correlated with GMV in both lingual gyri (p < 0.01 corrected). CONCLUSION: This study found VS to be associated with both functional and structural changes in the early and higher visual cortex, as well as the temporal cortex. These brain regions are involved in visual processing, memory, spatial attention, and cognitive control. We conclude that VS is not just confined to the visual system and that both functional and structural changes arise in VS patients, be it as an epiphenomenon or a direct contributor to the pathomechanism of VS. These in vivo neuroimaging biomarkers may hold potential as objective outcome measures of this so far purely subjective condition.

Real-World Clinical Experience With Idebenone in the Treatment of Leber Hereditary Optic Neuropathy.

BACKGROUND: Leber hereditary optic neuropathy (LHON) leads to bilateral central vision loss. In a clinical trial setting, idebenone has been shown to be safe and to provide a trend toward improved visual acuity, but long-term evidence of effectiveness in real-world clinical practice is sparse. METHODS: Open-label, multicenter, retrospective, noncontrolled analysis of long-term visual acuity and safety in 111 LHON patients treated with idebenone (900 mg/day) in an expanded access program. Eligible patients had a confirmed mitochondrial DNA mutation and had experienced the onset of symptoms (most recent eye) within 1 year before enrollment. Data on visual acuity and adverse events were collected as per normal clinical practice. Efficacy was assessed as the proportion of patients with either a clinically relevant recovery (CRR) or a clinically relevant stabilization (CRS) of visual acuity. In the case of CRR, time to and magnitude of recovery over the course of time were also assessed. RESULTS: At time of analysis, 87 patients had provided longitudinal efficacy data. Average treatment duration was 25.6 months. CRR was observed in 46.0% of patients. Analysis of treatment effect by duration showed that the proportion of patients with recovery and the magnitude of recovery increased with treatment duration. Average gain in best-corrected visual acuity for responders was 0.72 logarithm of the minimal angle of resolution (logMAR), equivalent to more than 7 lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Furthermore, 50% of patients who had a visual acuity below 1.0 logMAR in at least one eye at initiation of treatment successfully maintained their vision below this threshold by last observation. Idebenone was well tolerated, with most adverse events classified as minor. CONCLUSIONS: These data demonstrate the benefit of idebenone treatment in recovering lost vision and maintaining good residual vision in a real-world setting. Together, these findings indicate that idebenone treatment should be initiated early and be maintained more than 24 months to maximize efficacy. Safety results were consistent with the known safety profile of idebenone.

New Technologies for Outcome Measures in Glaucoma: Review by the European Vision Institute Special Interest Focus Group.

Glaucoma is the leading cause of irreversible blindness worldwide, with an increasing prevalence. The complexity of the disease has been a major challenge in moving the field forward with regard to both pathophysiological insight and treatment. In this context, discussing possible outcome measures in glaucoma trials is of utmost importance and clinical relevance. A recent meeting of the European Vision Institute (EVI) special interest focus group was held on "New Technologies for Outcome Measures in Retina and Glaucoma," addressing both functional and structural outcomes, as well as translational hot topics in glaucoma and retina research. In conjunction with the published literature, this review summarizes the meeting focusing on glaucoma.

New Technologies for Outcome Measures in Retinal Disease: Review from the European Vision Institute Special Interest Focus Group.

Novel diagnostic tools to measure retinal function and structure are rapidly being developed and introduced into clinical use. Opportunities exist to use these informative and robust measures as endpoints for clinical trials to determine efficacy and to monitor safety of therapeutic interventions. In order to inform researchers and clinician-scientists about these new diagnostic tools, a workshop was organized by the European Vision Institute. Invited speakers highlighted the recent advances in state-of-the-art technologies for outcome measures in the field of retina. This review highlights the workshop's presentations in the context of published literature.

Visual snow syndrome: a review on diagnosis, pathophysiology, and treatment.

PURPOSE OF REVIEW: Visual snow is considered a disorder of central visual processing resulting in a perturbed perception of constant bilateral whole-visual field flickering or pixelation. When associated with additional visual symptoms, it is referred to as visual snow syndrome. Its pathophysiology remains elusive. This review highlights the visual snow literature focusing on recent clinical studies that add to our understanding of its clinical picture, pathophysiology, and treatment. RECENT FINDINGS: Clinical characterization of visual snow syndrome is evolving, including a suggested modification of diagnostic criteria. Regarding pathophysiology, two recent studies tested the hypothesis of dysfunctional visual processing and occipital cortex hyperexcitability using electrophysiology. Likewise, advanced functional imaging shows promise to allow further insights into disease mechanisms. A retrospective study now provides Class IV evidence for a possible benefit of lamotrigine in a minority of patients. SUMMARY: Scientific understanding of visual snow syndrome is growing. Major challenges remain the subjective nature of the disease, its overlap with migraine, and the lack of quantifiable outcome measures, which are necessary for clinical trials. In that context, refined perceptual assessment, objective electrophysiological parameters, as well as advanced functional brain imaging studies, are promising tools in the pipeline.

Lateral geniculate nucleus volumetry at 3T and 7T: Four different optimized magnetic-resonance-imaging sequences evaluated against a 7T reference acquisition.

PURPOSE: The lateral geniculate nucleus (LGN) is an essential nucleus of the visual pathway, occupying a small volume (60-160 mm3) among the other thalamic nuclei. The reported LGN volumes vary greatly across studies due to technical limitations and due to methodological differences of volume assessment. Yet, structural and anatomical alterations in ophthalmologic and neurodegenerative pathologies can only be revealed by a precise and reliable LGN representation. To improve LGN volume assessment, we first implemented a reference acquisition for LGN volume determination with optimized Contrast to Noise Ratio (CNR) and high spatial resolution. Next, we compared CNR efficiency and rating reliability of 3D Magnetization Prepared Rapid Gradient Echo (MPRAGE) images using white matter nulled (WMn) and grey matter nulled (GMn) sequences and its subtraction (WMn-GMn) relative to the clinical standard Proton Density Turbo Spin Echo (PD 2D TSE) and the reference acquisition. We hypothesized that 3D MPRAGE should provide a higher CNR and volume determination accuracy than the currently used 2D sequences. MATERIALS AND METHODS: In 31 healthy subjects, we obtained at 3 and 7 T the following MR sequences: PD-TSE, MPRAGE with white/grey matter signal nulled (WMn/GMn), and a motion-corrected segmented MPRAGE sequence with a resolution of 0.4 × 0.4 × 0.4 mm3 (reference acquisition). To increase CNR, GMn were subtracted from WMn (WMn-GMn). Four investigators manually segmented the LGN independently. RESULTS: The reference acquisition provided a very sharp depiction of the LGN and an estimated mean LGN volume of 124 ±â€¯3.3 mm3. WMn-GMn had the highest CNR and gave the most reproducible LGN volume estimations between field strengths. Even with the highest CNR efficiency, PD-TSE gave inconsistent LGN volumes with the weakest reference acquisition correlation. The LGN WM rim induced a significant difference between LGN volumes estimated from WMn and GMn. WMn and GMn LGN volume estimations explained most of the reference acquisition volumes' variance. For all sequences, the volume rating reliability were good. On the other hand, the best CNR rating reliability, LGN volume and CNR correlations with the reference acquisition were obtained with GMn at 7 T. CONCLUSION: WMn and GMn MPRAGE allow reliable LGN volume determination at both field strengths. The precise location and identification of the LGN (volume) can help to optimize neuroanatomical and neurophysiological studies, which involve the LGN structure. Our optimized imaging protocol may be used for clinical applications aiming at small nuclei volumetric and CNR quantification.

Inter-Rater Reliability of Cyclotorsion Measurements Using Fundus Photography.

BACKGROUND: The foveo-papillary angle (FPA) on fundus photographs is the accepted standard for the measurement of ocular cyclotorsion. We assessed the inter-rater reliability of this method in healthy subjects and in patients with trochlear nerve palsies. PATIENTS AND METHODS: In this methodological study, fundus photographs of healthy subjects and of patients with trochlear nerve palsies were made with a fundus camera (Zeiss Fundus Camera FF 450 plus, Jena, Germany). Three independent observers measured the FPA on the fundus photographs of all subjects in synedra View (synedra View 16, Version 16.0.0.11, Innsbruck, Austria). RESULTS: One hundred and four eyes of 52 subjects (26 healthy controls and 26 patients) were assessed. The mean FPA of the healthy controls was 5.80 degrees (°) [± 0.44 standard error of the mean (SEM)] compared to 11.55° (± 0.80 SEM) for patients with trochlear nerve palsies. The inter-rater reliability of all measured FPAs showed an intraclass correlation coefficient (ICC) of 0.98 (95% CI 0.97 - 0.98). CONCLUSIONS: The inter-rater reliability of objective cyclotorsion measurements using fundus photographs was very high.

Multicenter reliability of semiautomatic retinal layer segmentation using OCT.

OBJECTIVE: To evaluate the inter-rater reliability of semiautomated segmentation of spectral domain optical coherence tomography (OCT) macular volume scans. METHODS: Macular OCT volume scans of left eyes from 17 subjects (8 patients with MS and 9 healthy controls) were automatically segmented by Heidelberg Eye Explorer (v1.9.3.0) beta-software (Spectralis Viewing Module v6.0.0.7), followed by manual correction by 5 experienced operators from 5 different academic centers. The mean thicknesses within a 6-mm area around the fovea were computed for the retinal nerve fiber layer, ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer, outer plexiform layer (OPL), and outer nuclear layer (ONL). Intraclass correlation coefficients (ICCs) were calculated for mean layer thickness values. Spatial distribution of ICC values for the segmented volume scans was investigated using heat maps. RESULTS: Agreement between raters was good (ICC > 0.84) for all retinal layers, particularly inner retinal layers showed excellent agreement across raters (ICC > 0.96). Spatial distribution of ICC showed highest values in the perimacular area, whereas the ICCs were poorer for the foveola and the more peripheral macular area. The automated segmentation of the OPL and ONL required the most correction and showed the least agreement, whereas differences were less prominent for the remaining layers. CONCLUSIONS: Automated segmentation with manual correction of macular OCT scans is highly reliable when performed by experienced raters and can thus be applied in multicenter settings. Reliability can be improved by restricting analysis to the perimacular area and compound segmentation of GCL and IPL.

Amiodarone-associated Optic Neuropathy-A Clinical Criteria-based Diagnosis?

Amiodarone-associated optic neuropathy (AAON) is a controversial diagnosis with possible impact on vital cardiac therapy decisions. This retrospective case series aims for application of distinguishing features of AAON versus non-arteritic ischaemic optic neuropathy (NAION): Bilaterality, mode of onset, degree of optic nerve dysfunction, structure of uninvolved disc (unilateral cases), and systemic toxic effects. Applying these criteria to patients with disc swelling under amiodarone, the authors identified four unilateral disc swellings, one with NAION-typical features only and three with one or more NAION-atypical features. All three sequential and six bilateral cases showed one or more NAION-atypical features. The 12 cases highlight the persisting diagnostic dilemma arising from diversity of presentation, lack of plausible pathomechanism, and controversial existence of the entity itself.