This study evaluates the long-term effects of selective retina therapy (SRT) on the retinal pigment epithelium (RPE) and neuroretina in patients with central serous chorioretinopathy. SRT was performed on 36 patients using a Nd:YLF-Laser at 527 nm (R:GEN®, Lutronic, Goyang-Si, Republic of Korea). A total of 994 titration spots were examined using up to three years’ multimodal imaging. Leakage in fluorescein angiography (FA) was observed after SRT in 523 lesions and resolved after one month. SRT lesions were not visible clinically, but appeared as brightly reflective areas in infrared and multicolor images. Normal morphology was observed in optical coherence tomography (OCT) immediately after SRT. After one month, thickening of the RPE and interdigitation zone changes were seen and disappeared after 539 ± 308 days. No RPE atrophies occurred during the observation period. Decreased fundus autofluorescence (FAF) was mostly observed directly after SRT followed by increased FAF at one month, which faded over time. A significant decrease in the number of visible lesions in the FA and FAF was observed within the three-year follow-up. OCT findings are consistent with animal studies showing SRT-related defect closure by hypertrophy and migration of neighboring cells without RPE atrophy or photoreceptor damage. This suggests that SRT is a safe treatment option for macular diseases and does not lead to retinal atrophy.
Introduction Retinal microvasculature is known to be altered in patients with Fabry disease (FD). We aimed to investigate the long-term changes in macular microvasculature and explore a reliable retinal biomarker for treatment monitoring in FD. Methods Prospective study of 26 eyes with FD followed up to 48 months (mean 24, range 8–48). OCT angiography (OCTA) images (2.9 × 2.9 mm) were obtained using Heidelberg Spectralis II at baseline and follow-up. Macular vessel area density (VAD, %) was measured in three layers: superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) in three peri-macular circular sectors (c1, c2, c3). Additionally, foveal avascular zone (FAZ) area (mm2) and horizontal and vertical diameters (µm) were assessed. Results VAD decreased over time in SVP, ICP (in sectors c2 and c3) and DCP (all sectors) (p < 0.04). VAD reduction was predominantly seen in treated FD patients. FAZ and horizontal diameters increased at follow-up in FD patients compared to baseline (p ≤ 0.025). Correlation analysis showed a moderate to strong negative correlation between VAD of SVP and DCP in the innermost circle and FAZ in treated patients (r = − 0.6; p < 0.0001). Conclusions This is the first long-term follow-up OCTA study in FD to our knowledge. A decrease in VAD, pronounced in the peripheral circle and deeper layers, as well as an enlargement of the FAZ could be observed over time. These changes reflect the vascular remodelling during the course of the disease. Interestingly, the reduction of VAD was more pronounced in treated patients. This could be a result of enzyme replacement therapy and could be potentially used as a reliable biomarker for monitoring the treatment of the disease. A baseline examination of VAD and FAZ before treatment initiation is meaningful. Larger studies are needed to establish the use of VAD and FAZ as biomarkers for treatment monitoring.
8 October 2023 in Orphanet Journal of Rare Diseases
Background: The goal of this study was to evaluate macular microvascular changes in patients with Fabry disease (FD) using optical coherence tomography angiography (OCTA) and to explore their correlation with laboratory and ocular findings. Methods: A total of 76 eyes (38 patients) and 48 eyes of 24 healthy controls were enrolled in this prospective study. Vessel Area Density (VAD) and Foveal Avascular Zone (FAZ) area were calculated on 2.9 × 2.9 mm OCTA images scanned with the Heidelberg Spectralis II (Heidelberg, Germany). VAD was measured in three layers: Superficial Vascular Plexus (SVP), Intermediate Capillary Plexus (ICP), and Deep Capillary Plexus (DCP). All scans were analyzed with the EA-Tool (Version 1.0), which was coded in MATLAB (The MathWorks Inc, R2017b). FAZ area was manually measured in full-thickness, SVP, ICP and DCP scans. Results: Average VAD in SVP, ICP and DCP was higher in Fabry disease patients than in controls (49.4 ± 11.0 vs. 26.5 ± 6.2, 29.6 ± 7.4 vs. 20.2 ± 4.4, 32.3 ± 8.8 vs. 21.7 ± 5.1 respectively, p < 0.001). Patients with cornea verticillata (CV) had a higher VAD in ICP and DCP compared to patients without CV ( p < 0.01). Patients with increased lysoGb3 concentration had a higher VAD in DCP when compared to patients with normal lysoGb3 concentration ( p < 0.04). There was no difference in VAD in patients with and without vascular tortuosity. However, a significantly higher VAD was observed in patients with vascular tortuosity compared to controls ( p < 0.03). Conclusions: Increased lysoGb3 and VAD in DCP could be reliable biomarkers of disease activity. Cornea verticillata could be adopted as a predictive biomarker for VAD changes and disease progression. The combination of cornea verticillata and increased VAD may serve as a diagnostic biomarker for Fabry disease, however due to the discrepancies in VAD values in various studies, further research has to be done to address this claim.
To evaluate wolfram as a photon and beta absorber in the management of uveal melanoma with radiotherapy, examining its potential ocular adverse effects and physiologic tolerance using an in vivo rabbit ocular model. A method of manufacturing implants from mixtures of wolfram and silicone was developed. Their shielding effect on the radiation of sources used in ocular brachytherapy was investigated by dosimetric measurement in an eye phantom as well as numerical simulations. Different wolfram implantation techniques, such as extraocular fixation of a wolfram-silicone implant (n = 1), vitrectomy with silicone oil and intravitreal injection of a wolfram-silicone oil suspension (n = 2), and concurrent attachment of a wolfram implant onto the sclera (n = 2), were tested to investigate the long-term effects of wolfram. A vitrectomy with silicone oil without wolfram implantation was carried out in 2 rabbits (n = 2), constituting the control group. The eyes were enucleated after 3 months for histologic analysis. Wolfram-silicone mixtures have been dosimetrically proven to be very effective radiation absorbers for use in ocular brachytherapy. Severe complications, such as endophthalmitis, secondary glaucoma, cornea decompensation, and vessel occlusion, were not documented in the tested rabbit eyes after the application of wolfram. Histologic examination of the bulbi after enucleation showed epiretinal gliosis without further pathologic findings in all eyes after vitrectomy. The results of this study show that wolfram and wolfram-silicone implants constitute a promising candidate as potential radiation shielding substrates.
Objectives: This retrospective study aimed to evaluate the effect of titration-guided focal selective retina therapy (SRT) for chronic central serous chorioretinopathy (cCSCR) and determine the need and effectiveness of re-treatment. Methods: SRT was performed in 60 eyes of 57 patients with cCSCR, targeting focal leakage points (FLP) using a Nd:YLF-Laser at 527 nm (R:GEN®, Lutronic, South Korea) titration-guided at 80% threshold, with 140 ms irradiation time, 100 Hz frequency, 1.7 µs pulse duration, 200 µm spot size. Best documented visual acuity (BDVA), peak height of subretinal fluid (SRF), height of SRF at the fovea, central retinal thickness (cRT) and total macular retinal volume (tRV) were measured. Results: A significant improvement in BDVA was observed up to 1 year compared to baseline ( p < 0.02). A limited analysis due to the small sample size showed no significant difference between the BDVA at baseline and 2-year ( n = 15) and 3-year ( n = 10) follow-ups. A significant decrease in the height of the SRF at the highest point and fovea and total retinal volume up to the 3-year follow-up was observed compared to the baseline ( p < 0.03). Thirty (50%) eyes of 30 patients required re-treatment, on average 9.2 ± 9.6 months after the initial SRT. This study found no predictors for the need of re-treatment. Conclusions: The study concludes that SRT is safe and shows anatomical and functional benefits for treating cCSCR. We recommend performing regular check-ups every three months and following a zero-fluid tolerance policy for re-treatment. Trial registration: German Clinical Trials Register ID: DRKS00031038, registration date: 2023-01-16
Proliferative vitreoretinopathy (PVR) is a vision-threatening fibrotic retinal disorder characterized by the epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells. In this study, we established a pathophysiologically relevant in vitro model by co-stimulating ARPE-19 cells with transforming growth factor beta 2 (TGFB2) and tumor necrosis factor-alpha (TNF), referred to as ‘TNT’, and evaluated the anti-fibrotic and anti-angiogenic effects of Nicotinamide (NAM), a vitamin B3 derivative previously reported to counteract fibrosis in various disease models. Confluent ARPE-19 cells were treated with TGFB2, TNF, or TNT for up to six days. EMT progression was assessed via immunocytochemistry, Western blotting, and collagen gel contraction assays. Live-cell imaging (LCI) combined with Hoechst 33342 nuclear staining and automated tracking using Fiji/TrackMate enabled real-time analysis of cell migration and multicellular aggregation. VEGFA secretion was quantified by ELISA. TNT stimulation induced synergistic EMT-like features, including cell elongation, directional migration, extracellular matrix (ECM) remodeling, gel contraction, and formation of multicellular aggregates. TrackMate-based analysis revealed coordinated nuclear migration under TNT conditions. VEGFA secretion was significantly elevated at early time points. NAM co-treatment reduced ECM protein expression (FN1, COL1A1), attenuated migration and contraction, and significantly lowered VEGFA release. This TNT-based ARPE-19 model represents a robust, live-cell-compatible in vitro system that mimics both fibrotic and pro-angiogenic aspects of PVR. It allows real-time assessment of EMT progression and is suitable for screening anti-fibrotic compounds. Our findings suggest that Nicotinamide mitigates both fibrotic and angiogenic responses in this model and may hold therapeutic potential for fibrotic retinal diseases.