Vasoactive peptides as biomarkers for the prediction of retinopathy of prematurity.

BACKGROUND: Retinopathy of prematurity (ROP) is a major complication in preterm infants. We assessed if plasma levels of midregional pro-atrial natriuretic peptide (MR-proANP) and C-terminal pro-endothelin-1 (CT-proET1) serve as early markers for subsequent ROP development in preterm infants <32 weeks gestation. METHODS: Prospective, two-centre, observational cohort study. MR-proANP and CT-proET1 were measured on day seven of life. Associations with ROP ≥ stage II were investigated by univariable and multivariable logistic regression models. RESULTS: We included 224 infants born at median (IQR) 29.6 (27.1-30.8) weeks gestation and birth weight of 1160 (860-1435) g. Nineteen patients developed ROP ≥ stage II. MR-proANP and CT-proET1 levels were higher in these infants (median (IQR) 864 (659-1564) pmol/L and 348 (300-382) pmol/L, respectively) compared to infants without ROP (median (IQR) 299 (210-502) pmol/L and 196 (156-268) pmol/L, respectively; both P < 0.001). MR-proANP and CT-proET1 levels were significantly associated with ROP ≥ stage II in univariable logistic regression models and after adjusting for co-factors, including gestational age and birth weight z-score. CONCLUSIONS: MR-proANP and CT-proET1 measured on day seven of life are strongly associated with ROP ≥ stage II in very preterm infants and might improve early prediction of ROP in the future. IMPACT: Plasma levels of midregional pro-atrial natriuretic peptide and C-terminal pro-endothelin-1 measured on day seven of life in very preterm infants show a strong association with development of retinopathy of prematurity ≥ stage II. Both biomarkers have the potential to improve early prediction of retinopathy of prematurity. Vasoactive peptides might allow to reduce the proportion of screened infants substantially.

Retinal vessel volume reference database derived from volume-rendered optical coherence tomography angiography.

Optical coherence tomography angiography (OCTA) enables three-dimensional reconstruction of the functional blood vessels in the retina. Therefore, it enables the quantification of 3D retinal vessel parameters such as surface area and vessel volume. In spite of the widespread use of OCTA, no representative volume-rendered vessel volume (VV) data are published to date. In this study, OCTA 3 × 3 mm macular cubes were processed with volume-rendering techniques to measure VV in 203 eyes from 107 healthy volunteers. Generalized linear models (GLM) were constructed to assess the impact of age, gender, visual acuity (VA), spherical equivalent (SE), and axial length (AL) on VV. Overall mean VV was 0.23 ± 0.05mm3. Age and axial length showed a negative correlation with VV. However, GLM model analysis found that AL exerted the most pronounced influence on VV. No statistically significant associations were identified between gender or between left and right eyes. This is the first study to assess 3D OCTA VV and its naturally occurring variations in a large series of healthy subjects. It offers novel insights into the characterization of normal retinal vascular anatomy in healthy individuals, contributing to a valuable reference for future research in this field.

Autologous internal limiting membrane transplantation achieves anatomic closure and functional improvement in the treatment of large, persistent macular holes.

PURPOSE: To evaluate the clinical outcome of subretinal autologous internal limiting membrane (ILM) transplantation during pars-plana vitrectomy for persistent full-thickness macular hole (FTMH) repair. METHODS: Retrospective, consecutive case series of 13 eyes (13 patients) undergoing small-incision vitrectomy with ILM transplantation and air tamponade for large persistent FTMH after prior unsuccessful vitrectomy with posterior hyaloid detachment and ILM peeling. MAIN OUTCOME MEASUREMENTS: For all eyes, high-definition spectral domain optical coherence tomography scans (SD-OCT Spectralis, Heidelberg Engineering GmbH, Germany) of the macula were routinely performed before surgery, 1 and 4 weeks after surgery, and at the final follow-up visit. Additionally, age, gender, axial length, macular hole diameter, biomicroscopic fundus evaluation and best-corrected visual acuity (BCVA) at baseline, 1 and 4 weeks after surgery, and at the final follow-up visit were analyzed. RESULTS: Anatomic closure was achieved in all 13 cases (100% success rate). Closure pattern was classified in accordance with to Rossi et al. (Graefe's Arch Clin Exp Ophthalmol 258(12):2629-2638, 2020). Mean baseline BCVA logMAR was 0.93, mean postoperative BCVA logMAR was 0.66 with a mean postoperative follow-up period of 11.4 months. No re-opening occurred during the observation period. CONCLUSIONS: Placing an autologous ILM-transplant in the subretinal space beneath the margin of the FTMH can support anatomic restauration and functional improvement in large, persistent FTMHs.

Relaxing radial retinal incisions for the treatment of persistent macular holes.

PURPOSE: Various surgical techniques have been described for managing persistent macular holes after an unsuccessful vitrectomy with internal limiting membrane (ILM) peeling. However, the closure and functional improvement rates after these procedures are limited. Therefore, the aim of this study was to evaluate the usefulness of radial retinal incisions (retinotomies) in eyes with persistent large macula holes despite previous vitrectomy with ILM peeling. DESIGN: In a retrospective case series, closure rate and best-corrected visual acuity (BCVA) were evaluated in eyes with persistent macular holes after an unsuccessful vitrectomy that included posterior vitreous detachment and ILM peeling. SUBJECTS: 22 eyes of 22 patients (10 men and 12 women) underwent re-vitrectomy with radial retinal incisions. All the patients had undergone an unsuccessful surgery before. METHODS: Small-incision re-vitrectomy with radial retinal incisions (retinotomies) and air tamponade was performed. MAIN OUTCOME MEASUREMENTS: For all eyes, high-definition SD-OCT scans (SD-OCT Spectralis, Heidelberg Engineering GmbH, Germany) of the macula were routinely performed before surgery; 1 week and 1 month after surgery; and at final follow-up. Additionally, age, gender, axial length, macular hole diameter, biomicroscopic fundus evaluation and best-corrected visual acuity (BCVA) in logMAR and Snellen at baseline, 1 and 4 months after operation, and at the final follow-up visit were analyzed. RESULTS: The mean baseline macular hole diameter was 668.5 ± 226.8 µm. At the final examination, 16 (72.72%) of the 22 macula holes were closed. Visual acuity increased in 17 eyes, was stable in 3 eyes, and decreased in 2 eyes owing to central retinal atrophy in both. The mean BCVA increased from logMAR 1.04 ± 0.29 at baseline to 0.57 ± 0.31 (Snellen 0.11 ± 0.05 to 0.33 ± 0.18). In all successful cases, macula hole closure was attained after 3 days, and none of the eyes showed macula hole recurrence. CONCLUSION: The results of this limited case series suggest that radial retinal incisions of the rim in persistent macula holes after initial surgery with ILM peeling increase the success rate of macula hole closure and results in a relevant increase in BCVA. However, as the number of eyes included in this series is limited, the results must be confirmed in a study with a larger sample size.

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.

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.

674 Cases of Late Postoperative Intraocular Lens Opacification of a Hydrophilic-Hydrophobic Acryl Intraocular Lens in Switzerland and Retrospective Opacification Risk Factor Assessment of 212 Cases.

PURPOSE: To report the prevalence of late postoperative opacification of a hydrophilic and hydrophobic acrylic intraocular lens (IOL) and to assess the risk factors in a subset of 212 eyes of patients referred to the University Eye Department in Basel, Switzerland. DESIGN: Retrospective case series. METHODS: A survey was performed at all large ophthalmological clinics in Switzerland regarding exchanged Lentis LS-502-1 lenses, and the number of affected eyes was counted. Moreover, consecutive patients who were referred to a tertiary clinic between September 2015 and November 2016 with Lentis LS-502-1 opacification were investigated. Peri- and postoperative charts, medical history, and topical and systemic medications were assessed. RESULTS: A total of 674 opacified Lentis LS-502-1 lenses have been reported in Switzerland, and 212 consecutive eyes of 182 patients were included in the study. All IOLs had a similar pattern of opacification with a yellowish, diffuse appearance, and most of them showed a small, paracentral, roundish area that was less affected or not at all. Arterial hypertension (73%), hypercholesterolemia (34%), and diabetes (21%) were the main associated systemic diseases, and statins (34%) and betablockers (34%) were the main treatments used. CONCLUSIONS: The prevalence of IOL opacification was 9.9%. No associated systemic eye disease or medications could be detected, which was implicated in the opacification process. The reason for opacification remains unclear, but it seems to be unrelated to the patient's state; therefore, it is attributed to primary calcification.

Primary Open-Angle Glaucoma Progression in Glaucoma Patients with Unchanged Topical Treatment over 3 Years - Retrospective Observational Cohort Analysis.

BACKGROUND: Lowering intraocular pressure (IOP) is a mainstay of glaucoma therapy. It is, however, still an open question whether a comparable level of long-term IOP lowering achieved by different medications results in comparable protection for the retinal ganglion cells. The purpose of this study was to retrospectively analyze glaucoma damage progression in two cohorts of primary open-angle glaucoma patients with different and unchanged therapy over a period of 3 years, and the main objective of this study was to determine possible differences in terms of structural [retinal nerve fiber layer thickness (RNFL)] and functional [visual field (VF)] outcome. PATIENTS AND METHODS: The retrospective observational cohort analysis compared two differently treated groups of glaucoma patients with their original, at study entry, topical therapy unchanged over 3 years. The main endpoint was the time course of RNFL thickness and VF mean defect (MD). RESULTS: Twenty-one eyes were included in each group. The first group (21 eyes) was on a fixed combination of timolol and dorzolamide twice a day and the second group on one drop of prostaglandin analog, either latanoprost alone (15 eyes) or travoprost alone (6 eyes), in an unchanged regimen over a period of 3 years. IOP in mmHg at baseline and at 36 months was 11.9 ± 2.4 and 13.0 ± 2.1 in the first, and 12.9 ± 3.0 and 14.1 ± 3.2 in the second group, respectively. RNFL thickness values in micrometers were at baseline and at 36 months 77.8 ± 12.3 and 76.6 ± 15.2 in the first, and 77.5 ± 15.2 and 72.8 ± 14.5 in the second group, respectively. VF MD in dB were 1.7 ± 2.5 and 1.2 ± 2.9 in the first, and 0.9 ± 2.3 and 0.7 ± 2.6 in the second group, respectively. CONCLUSION: Both groups had comparable baseline, as well as mean overall IOP. However, the course of IOP levels over time was different in the two groups, showing earlier and more pronounced long-term drift in the prostaglandin analog-treated group. RNFL thickness was comparable at baseline, however, RNFL thinning over time was more pronounced in the prostaglandin analog-treated group. There were no statistical differences between the groups in terms of VF MD at baseline and over time.

Retrospective Analysis of Prognostic Value of Optical Coherence Tomography Angiography for the Development of Glaucomatous Damage - One Year Follow-Up Retrospective Observational Cohort Analysis.

PURPOSE: Detecting glaucoma damage progression is an essential component of follow-ups in glaucoma patients. It is still unclear which of the currently available and routinely used parameters of glaucoma damage heralds the loss of retinal ganglion cells first. We analysed local hospital data on primary open-angle glaucoma (POAG) patients and looked for correlations between the optical coherence tomography (OCT) structural, OCT angiography (OCTA), and visual field (VF) parameters. PATIENTS AND METHODS: Results of eye examinations of POAG patients at baseline, 6 months, and 12 months were analysed. Inclusion criteria were, apart from the diagnosis of POAG, availability and quality of all modalities of examination data and no surgical intervention on the eyes during the observation period. Data on VF mean defect (MD), OCT peripapillary nerve fibre layer (RNFL), OCT macular ganglion cell layer, and OCTA, peripapillary and in the macula, were parameters of interest. Correlations of structural (OCT and OCTA) on one, and functional parameters (VF MD) on the other side, at baseline and as changing over time (first 6 months vs. second 6 months) were performed. RESULTS: All together, data from 78 eyes of 78 POAG patients were included in the analysis. Correlations at baseline were all highly significant (Spearman's r-coefficients between 0.31 and 0.8, all p < 0.05). None of the correlations of parameter changes over time were significant (all p > 0.05). CONCLUSION: Whereas a robust correlation was observed at baseline between the structural (OCT and OCTA) and functional (VF MD) parameters, none of the examination modality could predict a change in the other modalities during the 1-year period. Results confirm the necessity of regularly performing both the structural and functional examinations in our glaucoma patients.

Volumetric subfield analysis of cynomolgus monkey's choroid derived from hybrid machine learning optical coherence tomography segmentation.

This study aimed to provide volumetric choroidal readings regarding sex, origin, and eye side from healthy cynomolgus monkey eyes as a reference database using optical coherence tomography (OCT) imaging. A machine learning (ML) algorithm was used to extract the choroid from the volumetric OCT data. Classical computer vision methods were then applied to automatically identify the deepest location in the foveolar depression. The choroidal thickness was determined from this reference point. A total of 374 eyes of 203 cynomolgus macaques from Asian and Mauritius origin were included in the analysis. The overall subfoveolar mean choroidal volume in zone 1, in the region of the central bouquet, was 0.156 mm3 (range, 0.131-0.193 mm3). For the central choroid volume, the coefficient of variation (CV) was found of 6.3%, indicating relatively little variation. Our results show, based on analyses of variance, that monkey origin (Asian or Mauritius) does not influence choroid volumes. Sex had a significant influence on choroidal volumes in the superior-inferior axis (p ≤ 0.01), but not in the fovea centralis. A homogeneous foveolar choroidal architecture was also observed.

Hypothetical Switch of Anti-Vascular Endothelial Growth Factor in Neovascular Age-Related Macular Degeneration: An ARIES Post Hoc Analysis.

INTRODUCTION: Switching to an alternative anti-vascular endothelial growth factor (anti-VEGF) agent has been suggested for patients with neovascular age-related macular degeneration (nAMD) who have a suboptimal response to initial therapy. However, post hoc analyses of some studies have shown that continuation of initial anti-VEGF therapy is, in many cases, associated with stable visual outcomes or gradual gains. METHODS: This ARIES (ClinicalTrials.gov Identifier: NCT02581891) post hoc analysis describes outcomes in patients with treatment-naïve nAMD receiving treat-and-extend intravitreal aflibercept (IVT-AFL) for 104 weeks, who were identified as meeting criteria for an early hypothetical switch. Patients were categorized retrospectively according to six criteria (presence of central intraretinal and/or subretinal fluid at week 8 or 24, with/without a next planned treatment interval ≤ 8 weeks, and with/without gains in best-corrected visual acuity [BCVA] ≤ 5 letters [with absolute BCVA < 70 letters]). RESULTS: Hypothetical switch criteria were largely met due to the presence of central subretinal fluid rather than intraretinal fluid. Depending on the criterion, 8-46% of patients were considered to be hypothetical switchers. BCVA outcomes were not worse in the hypothetical switchers, irrespective of criteria. Using criteria of intraretinal/subretinal fluid at week 24 and a next planned treatment interval ≤ 8 weeks, mean changes in BCVA (letters) from baseline in hypothetical switchers and non-switchers were: + 6.1 (95% confidence interval [CI] 3.4, 8.8) and + 6.6 (95% CI 4.7, 8.6), respectively, at week 24; + 8.2 (95% CI 5.0, 11.3) and + 7.5 (95% CI 5.3, 9.7), respectively, at week 52; and + 5.7 (95% CI 1.3, 10.1) and + 3.4 (95% CI 0.1, 6.7), respectively, at week 104. CONCLUSIONS: In newly diagnosed nAMD, there appears little rationale for early switching from IVT-AFL since, with continuous proactive treatment, comparable visual gains can be achieved by patients meeting hypothetical switch criteria compared with those who initially respond well on a treat-and-extend regimen. However, further prospective studies are needed. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02581891. Video summary of the ARIES Post Hoc Analysis "Hypothetical Switch of Anti-Vascular Endothelial Growth Factor in Neovascular Age-Related Macular Degeneration" (MP4 54283 KB).

Feasibility and tolerability of ophthalmic virtual reality as a medical communication tool in children and young people.

PURPOSE: Virtual reality (VR) can be useful in explaining diseases and complications that affect children in order to improve medical communications with this vulnerable patient group. So far, children and young people's responses to high-end medical VR environments have never been assessed. METHODS: An unprecedented number of 320 children and young people were given the opportunity to interact with a VR application displaying original ophthalmic volume data via a commercially available tethered head-mounted display (HMD). Participants completed three surveys: demographics and experience with VR, usability and perceived utility of this technology and the Simulator Sickness Questionnaire. The second survey also probed participants for suggestions on improvements and whether this system could be useful for increasing engagement in science. RESULTS: A total of 206 sets of surveys were received. 165 children and young people (84 female) aged 12-18 years (mean, 15 years) completed surveys that could be used for analysis. 69 participants (47.59%) were VR-naïve, and 76 (52.41%) reported that they had previous VR experience. Results show that VR facilitated understanding of ophthalmological complications and was reasonably tolerated. Lastly, exposure to VR raised children and young people's awareness and interest in science. CONCLUSIONS: The VR platform used was successfully utilized and was well accepted in children to display and interact with volume-rendered 3D ophthalmological data. Virtual reality (VR) is suitable as a novel image display platform in ophthalmology to engage children and young people.

Dynamic volume-rendered optical coherence tomography pupillometry.

PURPOSE: To assess intrapupillary space (IPS) changes in healthy subjects with regard to decreased iris motility in patients with pseudoexfoliation glaucoma (PEXG) or non-arteritic anterior ischaemic optic neuropathy (NAION) in a feasibility study in a clinical environment. METHODS: Scotopic and photopic IPS measurements using three-dimensionally rendered swept-source optical coherence tomography (SS-OCT) data were obtained and compared for all subjects. Intrapupillary space (IPS) parameters were evaluated such as absolute volumetric differences, relative light response for volumetric ratios and pupillary ejection fraction (PEF) for functional contraction measurements. RESULTS: From a total of 122 IPS from 66 subjects, 106 IPS were eligible for comparison providing values for 72 normal, 30 PEXG and 4 NAION eyes. In healthy, PEXG and NAION subjects, scotopic overall mean IPS was 8.90, 3.45 and 4.16 mm3 , and photopic overall mean IPS was 0.87, 0.74 and 1.13 mm3 , respectively. Three-dimensional contractility showed a mean absolute difference of 8.03 mm3 for normals (defined as 100% contractility), 2.72 mm3 for PEXG (33.88% of normal) and 3.03 mm3 for NAION (38.50% of normal) with a relative light response ratio between scotopic and photopic volumes of 10.26 (100%), 4.69 (45.70%) and 3.67 (35.78%), respectively. Pupillary ejection fraction (PEF) showed a contractile pupillary emptying of 88.11% for normals, 76.92% for PEXG and 70.91% for NAION patients. CONCLUSION: This 3D pupillometry OCT assessment allows for quantitative measurements of pupil function, contractility and response to light. More specifically, PEF is presented as a potential (neuro)-pupillary outcome measure that could be useful in the monitoring of ophthalmic disorders that affect pupillary function.

Uncovering of intraspecies macular heterogeneity in cynomolgus monkeys using hybrid machine learning optical coherence tomography image segmentation.

The fovea is a depression in the center of the macula and is the site of the highest visual acuity. Optical coherence tomography (OCT) has contributed considerably in elucidating the pathologic changes in the fovea and is now being considered as an accompanying imaging method in drug development, such as antivascular endothelial growth factor and its safety profiling. Because animal numbers are limited in preclinical studies and automatized image evaluation tools have not yet been routinely employed, essential reference data describing the morphologic variations in macular thickness in laboratory cynomolgus monkeys are sparse to nonexistent. A hybrid machine learning algorithm was applied for automated OCT image processing and measurements of central retina thickness and surface area values. Morphological variations and the effects of sex and geographical origin were determined. Based on our findings, the fovea parameters are specific to the geographic origin. Despite morphological similarities among cynomolgus monkeys, considerable variations in the foveolar contour, even within the same species but from different geographic origins, were found. The results of the reference database show that not only the entire retinal thickness, but also the macular subfields, should be considered when designing preclinical studies and in the interpretation of foveal data.

Long-Term Clinical and Multimodal Imaging Findings in Patients with Disseminated Mycobacterium Chimaera Infection.

BACKGROUND: To analyze long-term ophthalmic clinical and multimodal imaging findings of disseminated Mycobacterium (M.) chimaera infection after cardiothoracic surgery among the Swiss Cohort. METHODS: Systemic and multimodal ophthalmic imaging and clinical findings including rate of recurrence were reviewed and correlated to a previously proposed classification system of choroidal lesions and classification of ocular disease. MAIN OUTCOMES MEASURES: long-term clinical and multimodal ocular imaging findings of M. chimaera. RESULTS: Twelve patients suffering from systemic infection from M. chimaera were included. Mean age at the first ophthalmic examination was 59 years (range from 48 to 66 years). Mean duration of the follow-up was 22.63 ± 17.8 months. All patients presented with bilateral chorioretinal lesions at baseline; 5 patients had additional signs, including optic disc swelling (2), choroidal neovascularization (1), retinal neovascularization (1) and cilioretinal vascular occlusion (1). Four recurrence events after discontinuation or adjustment of the antibiotic treatment were observed. Progressive choroiditis was seen in 5 patients under treatment, 4 of them deceased. CONCLUSIONS: Expertise from ophthalmologists is not only relevant but also critical for the assessment of the adverse drug effect of antimycobacterial treatment along with monitoring therapeutic response and identifying recurrences.