Background: This study aimed to evaluate the potential of human–machine interaction (HMI) in a deep learning software for discerning the malignancy of choroidal melanocytic lesions based on fundus photographs. Methods: The study enrolled individuals diagnosed with a choroidal melanocytic lesion at a tertiary clinic between 2011 and 2023, resulting in a cohort of 762 eligible cases. A deep learning-based assistant integrated into the software underwent training using a dataset comprising 762 color fundus photographs (CFPs) of choroidal lesions captured by various fundus cameras. The dataset was categorized into benign nevi, untreated choroidal melanomas, and irradiated choroidal melanomas. The reference standard for evaluation was established by retinal specialists using multimodal imaging. Trinary and binary models were trained, and their classification performance was evaluated on a test set consisting of 100 independent images. The discriminative performance of deep learning models was evaluated based on accuracy, recall, and specificity. Results: The final accuracy rates on the independent test set for multi-class and binary (benign vs. malignant) classification were 84.8% and 90.9%, respectively. Recall and specificity ranged from 0.85 to 0.90 and 0.91 to 0.92, respectively. The mean area under the curve (AUC) values were 0.96 and 0.99, respectively. Optimal discriminative performance was observed in binary classification with the incorporation of a single imaging modality, achieving an accuracy of 95.8%. Conclusions: The deep learning models demonstrated commendable performance in distinguishing the malignancy of choroidal lesions. The software exhibits promise for resource-efficient and cost-effective pre-stratification.

Background: To report on the outcome of intravitreal brolucizumab compared to aflibercept in patients with diabetic macular edema (DME). Methods: Prospective, observational, study in 35 eyes of 24 patients with a loading dose of five injections of 6 mg brolucizumab every 6 weeks (q6w, treatment-naïve eyes) or a minimum of two injections of brolucizumab q6w after the switch (recalcitrant DME eyes), followed by a treat and extend (T&E) regimen. The results were compared with 40 eyes of 31 DME patients who were treated with aflibercept. The data were obtained from the Berlin Macula Registry. The primary outcome measure was the change in best-corrected visual acuity (BCVA) at week 36. Secondary outcome measures were the change in central retinal thickness (CRT) and the treatment intervals until week 36. Results: BCVA increased significantly in treatment-naïve DME eyes treated with either brolucizumab (+0.12 logMAR, +6.4 letters, p = 0.03) or aflibercept (+0.19 logMAR, +9.5 letters, p = 0.001). In recalcitrant DME eyes, BCVA also increased significantly after switching to brolucizumab (+0.1 logMAR, +5 letters, p = 0.006) or aflibercept (+0.11 logMAR, +5.5 letters, p = 0.02). All treatment-naïve and recalcitrant DME eyes had a significant decrease in CRT after treatment with brolucizumab (p = 0.001 and p < 0.001) or aflibercept (p = 0.0002 and p = 0.03). At week 36, the mean treatment interval for brolucizumab was 11.3 weeks, while for aflibercept, it was 6.5 weeks for treatment-naïve eyes and 9.3 weeks vs. 5.3 weeks for pretreated eyes. Conclusions: In routine clinical practice, patients with treatment-naïve and recalcitrant DME showed a favorable response to brolucizumab and aflibercept therapy, with a reduced injection frequency after brolucizumab treatment.

There is early evidence of extraocular systemic signals effecting function and morphology in neovascular age-related macular degeneration (nAMD). The prospective, cross-sectional BIOMAC study is an explorative investigation of peripheral blood proteome profiles and matched clinical features to uncover systemic determinacy in nAMD under anti-vascular endothelial growth factor intravitreal therapy (anti-VEGF IVT). It includes 46 nAMD patients stratified by the level of disease control under ongoing anti-VEGF treatment. Proteomic profiles in peripheral blood samples of every patient were detected with LC-MS/MS mass spectrometry. The patients underwent extensive clinical examination with a focus on macular function and morphology. In silico analysis includes unbiased dimensionality reduction and clustering, a subsequent annotation of clinical features, and non-linear models for recognition of underlying patterns. The model assessment was performed using leave-one-out cross validation. The findings provide an exploratory demonstration of the link between systemic proteomic signals and macular disease pattern using and validating non-linear classification models. Three main results were obtained: (1) Proteome-based clustering identifies two distinct patient subclusters with the smaller one (n = 10) exhibiting a strong signature for oxidative stress response. Matching the relevant meta-features on the individual patient’s level identifies pulmonary dysfunction as an underlying health condition in these patients. (2) We identify biomarkers for nAMD disease features with Aldolase C as a putative factor associated with superior disease control under ongoing anti-VEGF treatment. (3) Apart from this, isolated protein markers are only weakly correlated with nAMD disease expression. In contrast, applying a non-linear classification model identifies complex molecular patterns hidden in a high number of proteomic dimensions determining macular disease expression. In conclusion, so far unconsidered systemic signals in the peripheral blood proteome contribute to the clinically observed phenotype of nAMD, which should be examined in future translational research on AMD.

Purpose: We aimed to determine the impact of artificial sweeteners (AS), especially saccharin, on the progression and treatment efficacy of patients with neovascular age-related macular degeneration (nAMD) under anti-vascular endothelial growth factor (anti-VEGF-A) treatment. Methods: In a cross-sectional study involving 46 patients with nAMD undergoing intravitreal anti-VEGF therapy, 6 AS metabolites were detected in peripheral blood using liquid chromatography - tandem mass spectrometry (LC-MS/MS). Disease features were statistically tested against these metabolite levels. Additionally, a murine choroidal neovascularization (CNV) model, induced by laser, was used to evaluate the effects of orally administered saccharin, assessing both imaging outcomes and gene expression patterns. Polymerase chain reaction (PCR) methods were used to evaluate functional expression of sweet taste receptors in a retinal pigment epithelium (RPE) cell line. Results: Saccharin levels in blood were significantly higher in patients with well-controlled CNV activity (P = 0.004) and those without subretinal hyper-reflective material (P = 0.015). In the murine model, saccharin-treated mice exhibited fewer leaking laser scars, lesser occurrence of bleeding, smaller fibrotic areas (P < 0.05), and a 40% decrease in mononuclear phagocyte accumulation (P = 0.06). Gene analysis indicated downregulation of inflammatory and VEGFR-1 response genes in the treated animals. Human RPE cells expressed taste receptor type 1 member 3 (TAS1R3) mRNA and reacted to saccharin stimulation with changes in mRNA expression. Conclusions: Saccharin appears to play a protective role in patients with nAMD undergoing intravitreal anti-VEGF treatment, aiding in better pathological lesion control and scar reduction. The murine study supports this observation, proposing saccharin's potential in mitigating pathological VEGFR-1-induced immune responses potentially via the RPE sensing saccharin in the blood stream.

Hintergrund: In der Pathophysiologie des Glaukoms spielen Mikroperfusionsstörungen in den papillenversorgenden Gefäßen eine bedeutende Rolle. Dabei wurde bislang angenommen, dass diese Störungen bei Normaldruckglaukompatienten mit bekannter vaskulärer Begleitsymptomatik besonders ausgeprägt zu finden seien. Patienten und Methoden: Der retrobulbäre Blutfluss wurde mittels Farbdopplersonografie (CDI) bei n = 18 Patienten mit einem gesicherten primär chronischen Offenwinkelglaukom (Hochdruckglaukom = HDG), n = 18 Patienten mit einem gesicherten Normaldruckglaukom (NDG) und vaskulärer Begleitsymptomatik wie Tinnitus, Migräne oder raynaudartigen Beschwerden und einer gesunden Kontrollpopulation (KGR) (n = 18) untersucht. Dabei wurden die maximale systolische Spitzengeschwindigkeit PSV, die enddiastolische Geschwindigkeit EDV und der Widerstandsindex RI in der A. ophthalmica (AO), der A. centralis retinae (ACR), der A. ciliaris posterior longus (ACPL) und der A. ciliaris posterior brevis (ACPB) ermittelt. Ergebnisse: In aufrecht sitzender Position fanden sich in der ACR und der ACPB in beiden Glaukomgruppen gegenüber der Kontrollgruppe signifikant erniedrigte Blutflussgeschwindigkeiten (PSV und EDV). In der HDG fanden sich im Vergleich zur KGR und zur NDG eine signifikant erniedrigte EDV und ein signifikant erhöhter RI in der ACPL. Außerdem findet sich in der HDG gegenüber der KGR ein signifikant erhöhter RI in der AO und in der ACPB. Diskussion: Beide Glaukomgruppen zeigen in der sitzenden Körperposition erniedrigte Blutflussgeschwindigkeiten in den kleinen retrobulbären Gefäßen. Dabei finden sich bei Normaldruckglaukompatienten unabhängig von dem Vorhandensein vasospastischer Begleitsymptome im Vergleich zu Hochdruckglaukompatienten nur geringe Unterschiede in der okulären Hämodynamik. Background: In the pathophysiology of open-angle glaucoma altered perfusion of the optic nerve head is of importance. Up to now these disturbances were presumed to be the chief cause of glaucomatous damage in patients with normal tension glaucoma showing other vascular disturbances like migraine or tinnitus. Patients and Methods: Peak systolic velocity (PSV) and end-diastolic velocity (EDV) were measured and the resistive index (RI) was calculated by colour Doppler imaging (CDI) in the ophthalmic artery (OA), central retinal artery (CRA) and in the short and long posterior ciliary arteries (SPCA, LPCA) in 18 patients with normal tension glaucoma (NTG), in 18 patients with high tension glaucoma (HTG) and in 18 normal control subjects. Results: In an upright sitting position both glaucoma groups showed statistically significant decreases in PSV and EDV in CRA and SPCA compared to the control subjects. HTG when compared to NTG and normal subjects showed statistically significant decreases of EDV and statistically significant increases of RI in LPCA. In addition, compared to normal subjects, HTG patients showed statistically significant increases of RI in both OA and SPCA. Discussion: Both glaucoma groups showed decreased blood flow velocities in the small retrobulbar vessels in an upright sitting position. Normal tension glaucoma patients with symptoms of vasospasms compared to patients with high tension glaucoma showed only small differences in ocular haemodynamics.