AI-driven discovery of blood xenobiotic biomarkers in neovascular age-related macular degeneration using iterative random forests.

PURPOSE: To investigate the xenobiotic profiles of patients with neovascular age-related macular degeneration (nAMD) undergoing anti-vascular endothelial growth factor (anti-VEGF) intravitreal therapy (IVT) to identify biomarkers indicative of clinical phenotypes through advanced AI methodologies. METHODS: In this cross-sectional observational study, we analyzed 156 peripheral blood xenobiotic features in a cohort of 46 nAMD patients stratified by choroidal neovascularization (CNV) control under anti-VEGF IVT. We employed Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) for measurement and leveraged an AI-driven iterative Random Forests (iRF) approach for robust pattern recognition and feature selection, aligning molecular profiles with clinical phenotypes. RESULTS: AI-augmented iRF models effectively refined the metabolite spectrum by discarding non-predictive elements. Perfluorooctanesulfonate (PFOS) and Ethyl ß-glucopyranoside were identified as significant biomarkers through this process, associated with various clinically relevant phenotypes. Unlike single metabolite classes, drug metabolites were distinctly correlated with subretinal fluid presence. CONCLUSIONS: This study underscores the enhanced capability of AI, particularly iRF, in dissecting complex metabolomic data to elucidate the xenobiotic landscape of nAMD and environmental impact on the disease. The preliminary biomarkers discovered offer promising directions for personalized treatment strategies, although further validation in broader cohorts is essential for clinical application.

[Vasculitis of the retina : Clinical aspects, diagnostics, management and treatment]. / Vaskulitis der Retina : Klinik, Diagnostik, Management und Therapie.

Inflammatory changes in the retinal vessels can be attributed to a wide range of etiologies. These include infections, intraocular and systemic autoimmune processes, general diseases and iatrogenic factors. As the endothelium of the retinal capillaries forms the inner blood-retinal barrier, a disruption of this structure is directly associated with consequences for the fluid electrolyte balance of the retina. Clinical sequelae can include leakage of the retinal vessels and macular edema, which are often functionally threatening and significantly reduce the quality of life of patients. As the eye can be affected as an "index organ", a work-up of the patient by the ophthalmologist is of great importance. In the age of "precision medicine", efforts are being made to gain new insights into the pathogenetic mechanisms of vasculitis through "omics" in order to develop innovative treatment concepts.

Fluocinolone Acetonide Implant for Uveitis: Dissecting Responder and Non-Responder Outcomes at a Tertiary Center.

Macular edema (ME) remains a primary cause of visual deterioration in uveitis. Visual acuity (VA) can often be maintained using corticosteroid depot systems. This study evaluated the efficacy of a fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN®) in treating non-infectious uveitis using real-world data. This retrospective analysis included 135 eyes subdivided into responders and non-responders. Central retinal thickness (CRT), VA, and intraocular pressure (IOP) were followed over time. A significant decrease in CRT and an increase in VA were observed in all eyes throughout the follow-up period (p < 0.01). An IOP increase (p = 0.028) necessitated treatment in 43% of eyes by Month 6. Non-responders were older (p = 0.004) and had been treated with more dexamethasone (DEX) implants (p = 0.04); 89.3% had a defect in the external limiting membrane (ELM) and inner/outer segment (IS/OS) zone (p < 0.001). Immunomodulatory therapy had no impact on treatment response. Pars plana vitrectomy (PPV) patients had a mean CRT reduction of 47.55 µm and a reduced effect by Month 24 (p = 0.046) versus non-PPV patients. We conclude that the FAc implant achieves long-term control of CRT and improves VA. Increases in IOP were manageable. Eyes with a previous PPV showed milder results. Data showed a correlation between older age, a damaged ELM and IS/OS zone, frequent DEX inserts, and poorer outcome measures.

Exploring the Impact of Saccharin on Neovascular Age-Related Macular Degeneration: A Comprehensive Study in Patients and Mice.

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.

Systemic Blood Proteome Patterns Reflect Disease Phenotypes in Neovascular Age-Related Macular Degeneration.

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.

Partial monovision achieved by unilateral implantation of a multifocal add-on lens with bilateral pseudophakia: evaluation and results.

PURPOSE: To assess the results of partial monovision (PMV) in comparison to a bilateral monofocal implantation (MMV). METHODS: The PMV group was treated bilaterally with a monofocal intraocular lens (IOL) implantation, followed 3 months later by the implantation of a multifocal AddOn® lens (+ 3.00 D) into the non-dominant eye. The MMV group received a bilateral monofocal IOL implantation intending to achieve a slight anisometropia (0.0 D/ - 0.50 D). The near visual acuity (UNVA), intermediate visual acuity (UIVA), distance visual acuity (UDVA), defocus curve, and Lang-Stereotest II were conducted uncorrected, binocular, and minimum 3 months after the last operation. For the contrast sensitivity test, the patients were refractively corrected. The Quality of Vision Questionnaire (QoV), Visual Function Questionnaire (VF-14), spectacle independence, and general satisfaction were also assessed. RESULTS: A total of 27 PMV patients and 28 MMV patients without ocular diseases relevant to visual acuity were examined. The PMV group was significantly better at UNVA (0.11 ± 0.08 logMAR vs 0.56 ± 0.16 logMAR) and between - 2.00 and - 4.00 D in the defocus curve (p < 0.001). At the UIVA, the PMV group was slightly better (0.11 ± 0.10 logMAR vs 0.20 ± 0.18 logMAR) but not significant (p = 0.054). The UDVA (- 0.13 ± 0.09 logMAR vs - 0.09 ± 0.14 logMAR) (p = 0.315) and contrast sensitivity (p = 0.667) revealed no differences between the groups. The stereo vision was in favor of PMV (p = 0.008). Spectacle independence was statistically better for PMV at distance, intermediate, and near (distance p = 0.012; intermediate p < 0.001; near p < 0.001). In the VF-14 Questionnaire, the PMV was statistically superior (p < 0.001). The QoV Questionnaire showed no differences regarding frequency and severity of visual disturbances. Both groups were highly satisfied (p = 0.509). CONCLUSION: Patients with PMV are more independent of glasses and are able to read without disadvantages in distance vision, due to halos and glare. The concept of PMV is well suited for the desire of eyeglass independence, without optical side effects.