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.

Ocular and systemic associations and heritability of retinal arterial wall-to-lumen ratios in a twin cohort.

PURPOSE: To investigate ocular and systemic factors associated with the retinal arterial wall-to-lumen ratio (WLR) and to determine the relative contribution of genetic and environmental variation to WLR in healthy adults. METHODS: This cross-sectional twin study included 78 monozygotic and 67 dizygotic same-sex twin pairs aged 58.4 ± 9.8 (mean ± SD) years. Lumen diameter (LD) and outer diameter (OD) of a superotemporal retinal artery were measured using adaptive optics fundus photography, and the WLR was calculated. Linear mixed model regression analysis of associations with WLR comprised the descriptive variables ocular axial length (AL), intraocular pressure (IOP), height, weight, body mass index (BMI), smoking, blood pressure, high density (HDL), low density (LDL) and very low density (VLDL) lipoproteins, total cholesterol and triglycerides. The relative influence of genes and environment on WLR was calculated through polygenetic modelling. RESULTS: Increasing age and arterial blood pressure were associated with a higher WLR, while increasing retinal artery OD and ocular AL were associated with a lower WLR. Sex, smoking status, BMI, IOP, cholesterol levels or triglycerides had no detectable impact on the WLR. Broad-sense heritability of WLR was 21% (95% CI: 1-41%), while environmental factors accounted for the remaining 79% of the interindividual variance (95% CI: 59-99%). CONCLUSION: Retinal artery wall thickness was closely linked to increasing age and higher arterial blood pressure, the latter being mediated by the environment over genes.

Laser-Induced Chorioretinal Anastomosis in Neurofibromatosis Type 1.

This case report describes a laser-induced chorioretinal anastomosis in a 38-year-old woman with neurofibromatosis type 1.

Small hard drusen and associated factors in early seniority.

PURPOSE: The purpose of this study was to examine the ocular and systemic risk profile of the fundus phenotype ≥ 20 small hard (macular) drusen (< 63 µm in diameter). METHODS: This single-center, cross-sectional study of 176 same-sex twin pairs aged 30 to 80 (median 60) years was a component of a framework study of the transition from not having age-related macular degeneration to having early AMD. Drusen categories assessed using fundus photography and optical coherence tomography included small hard drusen (diameter < 63 µm), intermediate soft drusen (63-125 µm), and large soft drusen (> 125 µm), of which the soft drusen are compatible with a diagnosis of AMD. RESULTS: Having ≥ 20 small hard drusen within or outside the macula was associated with increasing age, lower body mass index, shorter axial length, hyperopia, female sex, increasing high-density lipoprotein (HDL), high alcohol consumption, and with the presence of soft drusen. CONCLUSIONS: Having ≥ 20 small hard drusen was associated with some AMD-related risk factors, but not with smoking, increasing body mass index, and higher blood pressure. Having ≥ 20 small hard drusen was also associated with soft drusen, in agreement with previous studies. These findings suggest that small hard drusen are not an early manifestation of AMD but the product of a distinct process of tissue alteration that promotes the development of AMD or some subtype thereof.

Comparison of Spectral-Domain OCT versus Swept-Source OCT for the Detection of Deep Optic Disc Drusen.

Deep optic disc drusen (ODD) are located below Bruch's membrane opening (BMO) and may go undetected due to the challenges in imaging them. The purpose of this study is a head-to-head comparison of currently widely used imaging technologies: swept-source optical coherence tomography (SS-OCT; DRI OCT-1 Triton, Topcon) and enhanced depth imaging spectral-domain optical coherence tomography (EDI SD-OCT; Spectralis OCT, Heidelberg Engineering) for the detection of deep ODD and associated imaging features. The eyes included in this study had undergone high-resolution imaging via both EDI SD-OCT and SS-OCT volume scans, which showed at least one deep ODD or a hyperreflective line (HL). Grading was performed by three graders in a masked fashion. The study findings are based on 46 B-scan stacks of 23 eyes including a total of 7981 scans. For scan images with ODD located above or below the level of BMO, no significant difference was found between the two modalities compared in this study. However, for HLs and other features, EDI SD-OCT scan images had better visualization and less artifacts. Although SS-OCT offers deep tissue visualization, it did not appear to offer any advantage in ODD detection over a dense volume scan via EDI SD-OCT with B-scan averaging.

Heritability and Risk Factors of Incident Small and Large Drusen in the Copenhagen Twin Cohort Eye Study: A 20-Year Follow-Up.

INTRODUCTION: The transition from a normal fundus to one with early drusen (≥20 small hard drusen) to age-related macular degeneration (AMD) in the form of drusen ≥63 µm in diameter is of interest, because small hard drusen may be precursors of large drusen. Study of AMD precursor lesions may provide valuable insight into factors that initiate AMD. Here, the progression of drusen was studied over an interval of 20 years in a population-based twin cohort. METHODS: Single-center, 20-year follow-up of 138 twins include biometry, fundus optical coherence tomography, and fundus photography. Macular characteristics were hierarchically classified as (per eye) (1) <20 small hard drusen, (2) ≥20 small hard drusen, (3) drusen ≥63 µm, or (4) ≥20 small hard drusen combined with drusen ≥63 µm. Additive and dominant genetic effects as well as shared and nonshared environmental effects were analyzed in a bivariate biprobit model with a classic liability-threshold approach and polygenic modeling with random effects. RESULTS: Median participant age was 59 (range 41-66) years. Of 25 (18%) cases of incident macular drusen, 7 had ≥20 small hard drusen, and 18 had drusen ≥63 µm at follow-up, whereas no participant had developed both traits simultaneously. Smoking was associated with incident ≥20 small hard drusen (p = 0.04) and incident drusen ≥63 µm (p = 0.003). Having ≥20 small hard drusen at baseline was associated with incident drusen ≥63 µm at follow-up (p = 0.02). Development of drusen ≥63 µm was attributable to 49% genetic effects and 51% environmental effects. CONCLUSION: The risk of progressing from 0 to 19 small hard macular drusen per eye to having ≥20 small hard drusen or drusen ≥63 µm at follow-up was associated with smoking and genetic predisposition. Having ≥20 small hard drusen in the absence of drusen ≥63 µm at baseline was associated with incident drusen ≥63 µm when examined 20 years later. The study confirms that small hard macular drusen is a forewarning of AMD and that progression to AMD may be hindered by avoidance of smoking.

Long-term development of lens fluorescence in a twin cohort: Heritability and effects of age and lifestyle.

The blue-green autofluorescence of the ocular lens increases with age, glycemia and smoking, as the irreplaceable structural proteins of the lens slowly accumulate damage from the encounter with reactive molecular species. We have conducted a prospective study of lens autofluorescence over two decades in a twin cohort. The study included 131 phakic, non-diabetic adult twins (median age at follow-up 58 years, range 41-66 years) who were examined twice at an interval of 21 years. Change in anterior lens peak autofluorescence was analyzed in relation to age, current and baseline glycemia, cumulative smoking and heritability. The level of lens autofluorescence in the study population increased as a function of age and smoking (p ≤.002), but not as a function of glycemia (p ≥.069). Lens autofluorescence remained a highly heritable trait (90.6% at baseline and 93.3% at follow-up), but whereas the combined effect of age and cumulative smoking explained 57.2% of the variance in lens autofluorescence at baseline in mid-life, it only accounted for 31.6% at follow-up 21 years later. From mid to late adulthood, the level of blue-green fluorescence remained overwhelmingly heritable, but became less predictable from age, smoking habits and glycemic status. Presumably, as the lens ages, its intrinsic characteristics come to dominate over environmental and systemic factors, perhaps in a prelude to the development of cataract.

Heritability of retinal drusen in the Copenhagen Twin Cohort Eye Study.

PURPOSE: To study age- and sex-adjusted heritability of small hard drusen and early age-related macular degeneration (AMD) in a population-based twin cohort. METHODS: This was a single-centre, cross-sectional, classical twin study with ophthalmic examination including refraction, biometry, best-corrected visual acuity assessment, colour and autofluorescence fundus photography, and fundus optical coherence tomography. Grading and categorization of drusen was by diameter and location. RESULTS: The study enrolled 176 same-sex pairs of twins of mean (SD) age 58.6 (9.9) years. The prevalence of the four phenotypes ≥20 small hard macular drusen (largest diameter < 63 µm), ≥20 small hard extramacular drusen, intermediate drusen (63-125 µm) anywhere, and large drusen (>125 µm) anywhere was 12.4%, 36.4%, 5.8%, and 8.4%, respectively, and the respective heritabilities, adjusted for age and sex, were 78.2% [73.5-82.9], 69.1% [62.3-75.9], 30.1% [4.1-56.1], and 65.6% [26.4-100]. Age trajectory analysis supported a gradual transition to larger numbers of small hard drusen with increasing age. The heritability of ≥20 small hard drusen was markedly lower than the 99% found in the 40% overlapping twin cohort that was seen 20 years earlier. CONCLUSION: Numerous (≥20) small hard drusen and larger drusen that fit the definition of dry AMD were highly heritable. Small hard drusen counts increased with age. Decreasing heritability with increasing age suggests that the impact of behavioural and environmental factors on the development of small hard drusen increases with age.

Lens fluorescence and skin fluorescence in the Copenhagen Twin Cohort Eye Study: Covariates and heritability.

Lens and skin fluorescence are related to the systemic accumulation of advanced glycation end products, which is accelerated in diabetes. We have examined lens fluorescence and skin fluorescence in healthy adult twins. The study enrolled twins aged median 59 years from a national population-based registry. Diabetic individuals were excluded from analysis. The interrelatedness between fluorescence parameters and relations between fluorescence and age, current HbA1c and smoking pack years were examined using correlation tests and mixed model linear regression analyses. Broad-sense heritability was analyzed and compared for lens fluorescence, skin fluorescence and HbA1c. Lens fluorescence and skin fluorescence were crudely interrelated (R = 0.38). In linear regression analyses, age explained a larger fraction of the variance in lens fluorescence (R2 = 32%) than in skin fluorescence (R2 = 20%), whereas HbA1c explained smaller variance fractions (R2 = 3% and 8%, respectively) followed by smoking pack years (4% and 3%, respectively). In multivariate analyses, age, HbA1c and smoking pack years combined explained more of the variance in lens fluorescence (R2 = 35%) than in skin fluorescence (R2 = 21%), but the influence of HbA1c on lens fluorescence was not statistically significant (p = .2). Age-adjusted broad-sense heritability was 85% for lens fluorescence, 53% for skin fluorescence and 71% for HbA1c in best fitting heritability models. Both fluorescence parameters increased with age, current glycemia and cumulative smoking. Lens fluorescence was found to be a predominantly heritable trait, whereas skin fluorescence was more influenced by environmental factors and closer related to current glycemia. The results suggest that skin fluorophores have a faster turn-over than lens fluorophores.

Feasibility and Safety of a Coaxial Dual-Wavelength Optical Coherence Tomography Apparatus.

PURPOSE: To evaluate the feasibility and safety of a coaxial dual-wavelength optical coherence tomography (OCT) device (marked as Hydra-OCT). METHODS: Healthy participants without ocular pathology underwent retinal imaging using the Hydra-OCT allowing for simultaneous measurement of retinal scanning of 840 and 1,072 nm wavelength. Before and after measurement, best-corrected visual acuity and patients' comfort were assessed. Representative OCT images from both wavelengths were compared by 5 independent graders using a subjective grading scheme. RESULTS: A total of 30 eyes of 30 participants (8 females and 22 males) with a mean age of 26.5 years (range from 19 to 55 years) were included. Dual-wavelength image acquisition was made possible in each subject. The participant's effort and comfort assessment using the Hydra-OCT imaging revealed an equivalent value as compared to the commercially available OCT machine. No adverse events were reported, and visual acuity was not altered by the Hydra-OCT. Imaging between the systems was comparable. CONCLUSIONS: This study provides evidence for the feasibility and safety of a coaxial dual-wavelength OCT imaging method under real-life conditions. The novel Hydra-OCT imaging device may offer additional insights into the pathology of retinal and choroidal diseases.

OCT based interpretation of the optic nerve head anatomy in young adults with retinal vascular occlusions and ischemic optic neuropathy.

PURPOSE: To examine optic nerve head (ONH) anatomy in young adults with central retinal vein occlusion (CRVO), branch retinal vein occlusion (BRVO), central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO) or nonarteritic anterior ischemic optic neuropathy (NA-AION) in order to look for associated, potentially predisposing anomalies. METHODS: Cross-sectional study including 54 patients (ages 16-50 years) diagnosed from 2009 to 2018 with CRVO, BRVO, CRAO, BRAO, or NA-AION. Using Optical Coherence Tomography the presence of optic disc drusen (ODD), prelaminar hyperreflective lines and peripapillary hyperreflective ovoid mass-like structures (PHOMS), and determination of scleral canal size, retinal nerve fiber layer thickness (RNFLT) and macular ganglion cell layer thickness (GCLT) was obtained. Data for retinal vascular occlusion patients were grouped and analyzed together. RESULTS: ODD were found in 13% of all patients, 2% of retinal vascular occlusion patients and 67% of NA-AION patients (p < 0.0001). Prelaminar hyperreflective lines were found in 35% of all patients, 24% of retinal vascular occlusion patients and 89% of NA-AION patients (p = 0.0005). PHOMS were found in 20% of all patients, 13% of retinal vascular occlusion patients and 56% of NA-AION patients (p = 0.012). RNFLT was decreased in ODD patients compared to patients without ODD (p = 0.01). Scleral canal diameter and GCLT was not correlated with ODD, prelaminar hyperreflective lines or PHOMS. CONCLUSION: ODD, prelaminar hyperreflective lines and PHOMS were more frequent in NA-AION patients compared to retinal vascular occlusion patients. The prevalence of ODD in retinal vascular occlusion patients was similar to the reported prevalence in the general population.

Migration of an outer retinal element in a healthy child followed by longitudinal multimodal imaging.

PURPOSE: To describe the migration of an outer retinal element using longitudinal multimodal imaging. OBSERVATIONS: In the retina of a healthy 7-year-old girl, movement of a hyperreflective element of 15 µm extent was seen using optical coherence tomography (OCT), confocal scanning laser ophthalmoscopy (cSLO), and adaptive optics fundus photography (AO). On the OCT B-scan, the element initially appeared at the level of the outer limiting membrane with an umbra reaching the retinal pigment epithelium from where it gradually diminished and disappeared over 33 days. A corresponding disruption of the photoreceptor pattern on AO diminished over 52 days. CONCLUSIONS AND IMPORTANCE: This non-invasive observation of an isolated, cell-sized, migrating element in the human retina was made in vivo in the absence of confounding retinal disease or similar nearby elements. Based on prior preclinical observations we hypothesize that such a migrating element could be a macrophage. The case provides information about the time-scale and resolution needed for the monitoring of infiltrative processes in the retina.

Spectral-domain optical coherence tomography of retinal vessels in Waldenström's macroglobulinemia.

PURPOSE: To image retinal blood vessels in patients with Waldenström's macroglobulinemia using optical coherence tomography (OCT). METHODS: Retrospective case series examining fundus photographs and OCT scans of 16 eyes in eight patients with Waldenström's macroglobulinemia. Analyses included intravascular OCT reflectivity profiles and vessel diameters, and their relation to total immunoglobulin M (IgM) levels. RESULTS: In six out of eight patients, cross-sectional OCT scans of larger retinal vessels (diameter > 100 µm) showed normal intravascular reflectivity and retrovascular shadowing. In two patients with the highest total IgM > 60 g/l, altered intravascular reflectivity, distinct anterior and posterior vessel wall reflexes, and retrovascular hyposhadowing were seen. Normalization of the OCT reflectivity in these patients occurred after reduction of total IgM to < 17 g/l and was accompanied by decreasing venous tortuosity and disappearance of retinal haemorrhages and cotton wool spots. CONCLUSION: This study found that Waldenström's macroglobulinemia and total IgM > 60 g/l were associated with abnormal intravascular reflectivity and retrovascular shadowing on OCT. Awareness of these signs of hyperviscosity could potentially enable earlier detection of critical conditions in patients with Waldenström's macroglobulinemia and improve the assessment of severity and treatment effect.

Interdevice variability of central corneal thickness measurement.

PURPOSE: To evaluate variability of central corneal thickness measurement (CCT) devices using a hitherto unprecedented number of CCT devices. METHODS: CCT was measured consecutively in 122 normal corneas of 61 subjects with seven different devices using three distinct measurement technologies: Scheimpflug, Ultrasound, and Optical Coherence Tomography (OCT). Per device deviation from the mean CCT value per eye was used to determine which of the devices performed best, compared to the mean value. RESULTS: Cirrus OCT yielded the lowest deviation. Deviations of the individual devices from the mean CCT of each eye were (OS/OD) 12.8±5.0/14.9±9.4 µm for Topcon noncontact specular microscopy (NCSM), 11.3±5.9/10.6±7.3 µm for Pentacam, 10.7±5.2/10.4±4.8 µm for Spectralis OCT, 6.0±3.9/6.2±4.9 µm for Topcon DRI OCT, 5.1±3.4/5.9±10.3 µm for AngioVue OCT, 4.8±4.1/5.7±4.6 µm for US pachymetry, and 4.2±3.2/5.7±4.6 µm for Cirrus OCT. The maximum differences between US pachymetry and the other devices were very high (up to 120 µm). CONCLUSION: Central corneal thickness may be under- or overestimated due to high interdevice variations. Measuring CCT with one device only may lead to inappropriate clinical and surgical recommendations. OCT showed superior results.

THREE-DIMENSIONAL ANALYSIS OF SUBMACULAR PERFORATING SCLERAL VESSELS BY ENHANCED DEPTH IMAGING OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To analyze submacular perforating scleral vessels (PSVs) using enhanced depth imaging spectral domain optical coherence tomography (EDI-SDOCT). METHODS: Twenty-two eyes of 11 healthy women were included in this retrospective study. Central EDI-SDOCT scans (3 × 4.5 × 1.9 mm, 13.5 mm scan area) were acquired and postprocessed by denoising, manual sclera segmentation, and PSV investigated by five graders. RESULTS: Mean age was 22.4 ± 6.2 years. Mean refractive error was -0.44 ± 0.8 diopters. Mean axial length was 23.08 ± 0.63 mm. The coefficient of agreement for grading was good. Mean number of submacular PSVs was 0.33 ± 0.2 per mm (range from 0 to 9 per eye). Subfield analysis showed 0.2 ± 0.5 (range 0-2) and 2.1 ± 1.8 (range 0-7) vessels, respectively, for central 1-mm diameter and 3-mm diameter. Quadrant analysis showed 0.7 ± 0.9, 0.5 ± 0.9, 0.3 ± 0.6, and 0.4 ± 0.6 vessels, respectively for superior, inferior, nasal, and temporal quadrants. Total number of PSV showed no significant side difference (median difference 0.5, confidence interval -3.0 to 3.0, P = 0.94) or an influence of axial length (P = 0.16). CONCLUSION: This is the first description of three-dimensional EDI-SDOCT visualization of submacular PSV in healthy eyes. This method allows for in vivo imaging of a critical component of outer retinal perfusion at the posterior pole.

[Vision impairment at diagnosis of cancer - choroidal metastasis]. / Visusstörungen in der Tumordiagnostik - Aderhautmetastasen.

Choroidal metastasis represents the most common type of intraocular malignancy and preferably involves the posterior uveal tract. Breast and lung cancer - known or so far undiagnosed - are most frequently identified as the underlying tumor disease. The majority of patients diagnosed with uveal metastasis have additional metastatic manifestations elsewhere, so re-staging before treatment is recommended. The importance of a multidisciplinary approach is obvious. Early diagnosis and timely initiation of treatment are mandatory in case of vision-threatening situations. External beam radiation remains the therapy of choice. Overall survival of patients with uveal metastasis is limited, averaging six to twelve months. The other eye is frequently enough affected as well, justifying regular ophthalmologic follow-up during the further course of the disease.

La tumeur intraoculaire la plus fréquente est un cancer métastatique qui se présente fréquemment dans la choroïde. Elle provient d'un cancer primaire (connu ou inconnu) situé le plus souvent au niveau du sein ou du poumon. La majorité des patients souffrant de métastases choroïdiennes présentent également d'autres métastases. C'est pourquoi une restadification s'impose. La nécessité d'un suivi multidisciplinaire est évidente. Si l'acuité visuelle est menacée, il est vital que le diagnostic et le traitement interviennent rapidement. La modalité thérapeutique privilégiée est la radiothérapie externe. La survie des patients souffrant de métastases choroïdiennes ne dépasse pas six à douze mois en moyenne. L'autre œil peut être affecté lui aussi. Par conséquent, des examens ophtalmologiques doivent avoir lieu régulièrement.

Macular pigment density at the site of altered fundus autofluorescence.

BACKGROUND: The purpose of our study was to determine whether abnormalities of increased or decreased fundus autofluorescence (FAF) are associated with local changes in macular pigment (MP) optical density in patients with age-related maculopathy (ARM) and macular degeneration (ARMD). METHODS: FAF imaging and MP measurement was performed through dilated pupils using a modified confocal scanning laser ophthalmoscope (HRA, Heidelberg Engineering, Germany) according to a standard protocol. Two-wavelength autofluorescence method was employed for determination of local macular pigment optical density (LMPOD). Image analysis and measurement of LMPOD at the area of altered FAF was performed using Heidelberg Eye Explorer Software. Mean values of LMPOD at the site of FAF abnormality were compared to an adjacent location with normal background FAF of the same image. RESULTS: Sixty-three eyes of 63 patients (28 male, 35 female, mean age 75.8 ± 8.8 years) were included in this analysis. Group 1 comprised 31 cases with focal increased FAF. Mean LMPOD in the area of increased FAF was 0.073 ± 0.083 compared to 0.075 ± 0.074 in the adjacent area of normal FAF. Group 2 comprised 32 cases of focal decreased FAF. Mean LMPOD in the area of decreased FAF was -0.004 ± 0.088 compared 0.053 ± 0.075 in the adjacent area of normal FAF. The site of increased FAF showed no significant difference in LMPOD (p = 0.927) compared to adjacent areas of normal FAF, while areas of decreased FAF revealed significantly lower LMPOD (p = 0.001) compared to adjacent areas of normal FAF. CONCLUSIONS: Focal increases of FAF due to ARM or ARMD did not lead to change in LMPOD. Presumably, retinal layers containing MP are unaffected by these processes. For lesions exhibiting focal decreased FAF, a reduction of LMPOD cannot be excluded. Further studies are needed to investigate MP in the course of disease.