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.

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.

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.

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.

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.

Predictors of short-term visual outcome after anti-VEGF therapy of macular edema due to central retinal vein occlusion.

PURPOSE: The purpose of this study was to analyze predictive factors for best-corrected visual acuity (BCVA) after anti-VEGF treatment in patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO). METHODS: This prospective study enrolled treatment-naive patients with ME secondary to CRVO. BCVA, ophthalmoscopy, fundus photography, and spectral domain optical coherence tomography (SD-OCT) imaging were performed. SD-OCT was analyzed for integrity of the external limiting membrane (ELM), photoreceptor inner segments (IS), and outer segments (OS). Patients were treated with intravitreal bevacizumab (1.25 mg) or ranibizumab (0.5 mg). BCVA outcome was analyzed 4 weeks after the first injection. RESULTS: Sixty-two eyes of 62 patients (39 men, 23 women; mean age: 67 ±16 years) were included. In 55%, the ELM was intact. These eyes also showed intact photoreceptor IS/OS in horizontal and vertical single scans. Disturbed ELM was seen in 45% and was accompanied by focal disintegration of IS/OS. Four weeks after injection, 58% showed clinically relevant increases of BCVA (≥5 letters). Mean BCVA ranged from 20 to 86 letters. The mean BCVA increase was 18 ± 12 letters in eyes with intact ELM compared with 4 ± 10 letters with disturbed ELM (P < 0.001). CONCLUSIONS: Depending on the integrity of the outer retinal layers, the authors observed rapid and clinically relevant improvement in BCVA after the first anti-VEGF injection. In the development of an optimal treatment regime, the indication for treatment and re-treatment should be based on functional and morphologic findings, such as the deterioration of outer retinal layers. Intact ELM in SD-OCT imaging is associated with better visual outcomes after intravitreal anti-VEGF treatment in patients with ME secondary to CRVO.

Multimodal registration procedure for the initial spatial alignment of a retinal video sequence to a retinal composite image.

Accurate placement of lesions is crucial for the effectiveness and safety of a retinal laser photocoagulation treatment. Computer assistance provides the capability for improvements to treatment accuracy and execution time. The idea is to use video frames acquired from a scanning digital ophthalmoscope (SDO) to compensate for retinal motion during laser treatment. This paper presents a method for the multimodal registration of the initial frame from an SDO retinal video sequence to a retinal composite image, which may contain a treatment plan. The retinal registration procedure comprises the following steps: 1) detection of vessel centerline points and identification of the optic disc; 2) prealignment of the video frame and the composite image based on optic disc parameters; and 3) iterative matching of the detected vessel centerline points in expanding matching regions. This registration algorithm was designed for the initialization of a real-time registration procedure that registers the subsequent video frames to the composite image. The algorithm demonstrated its capability to register various pairs of SDO video frames and composite images acquired from patients.

Effects of ranibizumab in patients with subfoveal choroidal neovascularization attributable to age-related macular degeneration.

PURPOSE: To demonstrate not only prevention of vision loss but also improvement in best-corrected visual acuity (BCVA) after treatment with ranibizumab on a variable-dosing regimen over 24 months in patients with age-related macular degeneration (AMD). DESIGN: Interventional case series. SETTING: Institutional. STUDY POPULATION: One hundred and thirty-eight eyes of 138 patients treated intravitreally with 0.5 mg ranibizumab (Lucentis; Novartis, Basel, Switzerland). Age above 50 years, BCVA 0.2 to 1.2 logarithm of the minimal angle of resolution (logMAR), primary or recurrent subfoveal choroidal neovascularization (CNV) secondary to AMD. OBSERVATION PROCEDURES: After single initial treatment, monthly follow-up examination. Retreatment in case of one of the following: sign of subretinal fluid or intraretinal edema, increase in central retinal thickness (CRT) on optical coherence tomography (OCT), active CNV on fluorescein angiography, increase of metamorphopsia, and loss of BCVA > 5 letters on Early Treatment Diabetic Retinopathy Study (ETDRS) chart. MAIN OUTCOME MEASURES: Compared with baseline: proportion of eyes gaining > or = 15 letters, proportion of eyes losing or gaining < 15 letters, change in CRT. RESULTS: After 24 months, 30% of eyes gained > or = 15 letters. After 24 months, 55% of eyes lost or gained < 15 letters. Mean CRT of 386 +/- 145 microm at baseline was significantly reduced to 211 +/- 39 microm after 24 months (P = .036). Mean injection number per patient was 5.6 +/- 2.9 and 4.3 +/- 3.8 from baseline to month 12 and month 12 to 24, respectively. CONCLUSION: Intravitreal ranibizumab on a variable-dosing regimen was effective in significantly increasing mean BVCA and reducing CRT. This beneficial outcome was achieved with a low-rate of mild ocular adverse effects among our patients.

Macular thickness measurements in healthy eyes using six different optical coherence tomography instruments.

PURPOSE: To compare central retinal thickness (CRT) measurements in healthy eyes by different commercially available OCT instruments and to compare the intersession reproducibility of such measurements. METHODS: Six different OCT instruments (Stratus OCT [Carl Zeiss Meditec, Inc. Dublin, CA], SOCT Copernicus [Reichert/Optopol Technology, Inc., Depew, NY], Spectral OCT/SLO [Opko/OTI, Inc., Miami, FL], RTVue-100 [Optovue Corp., Fremont, CA], Spectralis HRA+OCT [Heidelberg Engineering, Inc., Heidelberg, Germany], and Cirrus HD-OCT [Carl Zeiss Meditec, Inc.]) were used to assess CRT in both eyes of healthy subjects. Measurements were performed in two different sessions on the same day with each of the systems. From these measurements, the mean CRT was calculated. For the assessment of the intersession reproducibility of the instruments, we calculated the coefficient of the variation of test-retest variation. RESULTS: Twenty healthy subjects were included in the study. Compared with the Stratus OCT all spectral OCT instruments showed significantly higher CRTs. The Spectralis HRA+OCT and Cirrus HD-OCT showed similar CRT values but significantly higher values than did all other instruments. The coefficients of variation for repeated measurements was 3.33% for the Stratus OCT, 0.46% for the Spectralis HRA+OCT, 3.09% for the Cirrus HD-OCT, 2.23% for the OCT/SLO, 2.77% for the RTVue-100 OCT, and for the SOCT 3.5%, respectively. discussion. The six OCT systems provided different results for CRT. The measurements with the Stratus OCT showed the lowest thicknesses, whereas those with the Cirrus HD-OCT and Spectralis HRA+OCT yielded the highest ones. These discrepancies can be explained by the differences in the retinal segmentation algorithms used by the various OCT systems. Whereas the Spectralis HRA+OCT and Cirrus HD-OCT include the RPE layer in the retinal segmentation, the other instruments do not. The data imply that the different OCT systems cannot be used interchangeably for the measurement of macular thickness.