Search Results (16)

This pilot study explored whether the ceruloplasmin (CP) and ferritin (FT) levels in ocular fluids could serve as biomarkers for early neurodegenerative diseases (Alzheimer’s, Parkinson’s, and other dementias). CP and FT are known to modulate neurodegenerative tissue responses. We analysed aqueous and vitreous samples from 26 patients (8M/18F, aged 60–85) who were undergoing elective vitreoretinal (VR) surgery. Of these, 14 had idiopathic epiretinal membranes (ERMs), 6 had idiopathic macular holes (MH), and 6 were patients with Alzheimer’s disease (AD) who presented with VR disorders (VRDs). CP, FT, and selected neuroinflammatory mediators such as interferon γ (IFN-γ), interleukin (IL-6), vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) were quantified. Odds ratio analysis was applied to assess the CP/FT ratio’s association with subretinal drusen. We found distinct CP and FT profiles in VRD samples. In aqueous fluid, the CP increased and the FT decreased in early-stage ERM, which reduced the CP/FT ratio. Similar patterns were observed in vitreous fluid. The CP levels correlated with the VEGF (aqueous), IL-4 (vitreous), NGF, and BDNF levels; FT correlated with IL-6 and NGF. A higher CP/FT ratio was associated with increased risk for neurodegenerative conditions. Our findings support the quantification of CP and FT in ocular fluids as a promising approach for identifying early neurodegenerative changes and suggest that the CP/FT ratio may be linked to drusen imaging and clinical neurodegenerative history. Full article

Previous studies reported the expression of toll-like receptors (TLRs), merely TLR2 and TLR4, and complement fragments (C3a, C5b9) in vitreoretinal disorders. Other than pathogens, TLRs can recognize endogenous products of tissue remodeling as damage-associated molecular pattern (DAMPs). The aim of this study was to confirm the expression of TLR2 and TLR4 in the fibrocellular membranes and vitreal fluids (soluble TLRs) of patients suffering of epiretinal membranes (ERMs) and assess their association with disease severity, complement fragments and inflammatory profiles. Twenty (n = 20) ERMs and twelve (n = 12) vitreous samples were collected at the time of the vitrectomy. Different severity-staged ERMs were processed for: immunolocalization (IF), transcriptomic (RT-PCR) and proteomics (ELISA, IP/WB, Protein Chip Array) analysis. The investigation of targets included TLR2, TLR4, C3a, C5b9, a few selected inflammatory biomarkers (Eotaxin-2, Rantes, Vascular Endothelial Growth Factor (VEGFA), Vascular Endothelial Growth Factor receptor (VEGFR2), Interferon-γ (IFNγ), Interleukin (IL1β, IL12p40/p70)) and a restricted panel of matrix enzymes (Matrix metalloproteinases (MMPs)/Tissue Inhibitor of Metallo-Proteinases (TIMPs)). A reduced cellularity was observed as function of ERM severity. TLR2, TLR4 and myD88 transcripts/proteins were detected in membranes and decreased upon disease severity. The levels of soluble TLR2 and TLR4, as well as C3a, C5b9, Eotaxin-2, Rantes, VEGFA, VEGFR2, IFNγ, IL1β, IL12p40/p70, MMP7 and TIMP2 levels were changed in vitreal samples. Significant correlations were observed between TLRs and complement fragments and between TLRs and some inflammatory mediators. Our findings pointed at TLR2 and TLR4 over-expression at early stages of ERM formation, suggesting the participation of the local immune response in the severity of disease. These activations at the early-stage of ERM formation suggest a potential persistence of innate immune response in the early phases of fibrocellular membrane formation. Full article

Background: To descriptively report the advantages and the feasibility of microscope-integrated intraoperative optical coherence tomography (i-OCT) in managing different vitreoretinal diseases in a real-life setting. Methods: We conducted an observational retrospective study involving 265 eyes that underwent elective retinal surgery and intraoperative OCT between 1 September 2018 and 1 October 2022 at Eyecare Clinic (Brescia, Italy). Results: 52 epiretinal membranes, 30 retinal detachments, 60 high myopic eyes, 30 choroidal transplants, 40 macular holes, and 32 vitreo-proliferative retinopathies underwent vitreoretinal surgery and intraoperative OCT scans. The i-OCT was a useful diagnostic exam for all cases and significantly influenced our surgical management. Conclusions: i-OCT is a helpful surgical tool in ophthalmic surgery as it provides real-time feedback of tissue anatomy to surgeons, thereby guiding decision-making. Moreover, it provides additional information on the microarchitectural changes after instrument–tissue interactions, further guiding procedures when necessary and possibly reducing unessential surgical maneuvers. Full article

Optical coherence tomography (OCT) is a non-invasive imaging technique for high-resolution, cross-sectional tissue imaging of the eye. During the past two and a half decades, OCT has become an essential tool in ophthalmology. It is a painless method for examining details of ocular structures in vivo with high resolution that has revolutionized patient care following and treating scleritis patients. Methods: Twenty-four patients diagnosed with scleritis were selected for this study. All of the patients went through basic ophthalmological examinations, such as visual acuity testing (VA), intraocular pressure measurement (IOP), slit lamp examination, ophthalmoscopic examination, and OCT. OCT examinations were taken by SD-OCT Spectralis OCT system (Heidelberg Engineering, Heidelberg, Germany). Results: Twenty-seven eyes of 24 patients (7 males and 17 females) were included in this study, who were diagnosed with scleritis. OCT examinations showed epiretinal membrane (ERM) in three patients (12%), cystoid macular edema (CME) (three cases, 12%), diffuse macular edema (DME) (one case, 4%), and serous retinal detachment (SRD) (one case, 4%). Conclusions: OCT proved to be a valuable, non-invasive method for detecting macular pathology in patients with scleritis. Despite the best treatment regimen applied, macular involvement resulting in reduced visual acuity (VA) can develop, which we could detect with OCT since macular edema (ME) is the leading cause of decreased vision due to the damaged outer blood–retina barrier (BRB) in inflammation. OCT investigation is a highly important method for early detection of ocular complications in scleritis in order to prevent blindness. Full article

Epiretinal membranes (ERMs) are sheets of tissue that pathologically develop in the vitreoretinal interface leading to progressive vision loss. They are formed by different cell types and by an exuberant deposition of extracellular matrix proteins. Recently, we reviewed ERMs’ extracellular matrix components to better understand molecular dysfunctions that trigger and fuel the onset and development of this disease. The bioinformatics approach we applied delineated a comprehensive overview on this fibrocellular tissue and on critical proteins that could really impact ERM physiopathology. Our interactomic analysis proposed the hyaluronic-acid-receptor cluster of differentiation 44 (CD44) as a central regulator of ERM aberrant dynamics and progression. Interestingly, the interaction between CD44 and podoplanin (PDPN) was shown to promote directional migration in epithelial cells. PDPN is a glycoprotein overexpressed in various cancers and a growing body of evidence indicates its relevant function in several fibrotic and inflammatory pathologies. The binding of PDPN to partner proteins and/or its ligand results in the modulation of signaling pathways regulating proliferation, contractility, migration, epithelial–mesenchymal transition, and extracellular matrix remodeling, all processes that are vital in ERM formation. In this context, the understanding of the PDPN role can help to modulate signaling during fibrosis, hence opening a new line of therapy. Full article

Purpose: To describe the feasibility of intraoperative digital visualization and its contribution to the enhancement of macular pigmentation visualization in a prospective series of macular surgery interventions. Materials and Methods: A prospective, single-center, single-surgeon study was performed on a series of 21 consecutive cases of vitrectomy for various types of macular surgery using a 3D visualization system. Two optimized filters were applied to enhance the visualization of the macular pigment (MP). For filter 1, cyan, yellow, and magenta color saturations were increased. Filter 2 differed from filter 1 only in having a lower level of magenta saturation for the green-magenta color channel. Results: Optimized digital filters enhanced the visualization of the MP and the pigmented epiretinal tissue associated with the lamellar and macular holes. In vitreomacular traction surgery, the filters facilitated the assessment of MP integrity at the end of surgery. Filter 1 enhanced MP visualization most strongly, with the MP appearing green and slightly fluorescent. Filter 2 enhanced MP visualization less effectively but gave a clearer image of the retinal surface, facilitating safe macular peeling. Conclusion: Optimized digital filters could be used to enhance MP and pigmented epiretinal tissue visualization during macular surgery. These filters open new horizons for future research and should be evaluated in larger series and correlated with intraoperative OCT. Full article

Pathological tissue on the surface of the retina that can be of different etiology and pathogenesis can cause changes in the retina that have a direct consequence on vision. Tissues of different etiology and pathogenesis have different morphological structures and also different macromolecule compositions usually characteristic of specific diseases. In this study, we evaluated and compared biochemical differences among samples of three different types of epiretinal proliferations: idiopathic epiretinal membrane (ERMi), membranes in proliferative vitreoretinopathy (PVRm), and proliferative diabetic retinopathy (PDRm). The membranes were analyzed by using synchrotron radiation-based Fourier transform infrared micro-spectroscopy (SR-FTIR). We used the SR-FTIR micro-spectroscopy setup, where measurements were set to achieve a high resolution that was capable of showing clear biochemical spectra in biological tissue. We were able to identify differences between PVRm, PDRm, and ERMi in protein and lipid structure; collagen content and collagen maturity; differences in proteoglycan presence; protein phosphorylation; and DNA expression. Collagen showed the strongest expression in PDRm, lower expression in ERMi, and very low expression in PVRm. We also demonstrated the presence of silicone oil (SO) or polydimethylsiloxane in the structure of PVRm after SO endotamponade. This finding suggests that SO, in addition to its many benefits as an important tool in vitreoretinal surgery, could be involved in PVRm formation. Full article

Background: The aim of this study is to provide intraoperative data demonstrating a significant difference in the membrane peeling dynamics performed under a perfluorocarbon (PFCL) bubble, compared to normal balanced saline solution (BSS). Methods: This is a prospective, interventional, single-center study on a series of 36 consecutive eyes of 36 patients affected by primary epiretinal membrane (ERM). Eighteen eyes underwent standard ERM peeling, while 18 eyes received a PFCL-assisted procedure. Intraoperative optical coherence tomography (iOCT) B-Scans were collected to evaluate the displacement angle (DA) between the underlying retinal plane and the flap of epiretinal tissue, along with the number of times the surgeon had to grab the flap during the intervention. Follow-up visits were carried out at postoperative week 1 and months 1, 3 and 6. Results: The mean DA was 164.8° ± 4.0 in the PFCL-assisted group and 119.7° ± 8.7 in the standard group, with a statistically significant difference between groups (p < 0.001). Moreover, we found a significant difference in the amount of ERM grabs between the two groups (7.2 ± 2.5 in the PFCL-assisted group vs. 10.3 ± 3.1 in the standard group, p = 0.005). The mean BCVA and metamorphopsia significantly improved in both groups (p < 0.05), with no significant intergroup difference at all follow-up visits. Similarly, CST significantly decreased in both groups, and final CST was similar between the two groups (p = 0.719). Overall, three eyes in the standard group developed postoperative dissociated optic nerve fiber layer (DONFL, 16.6%), compared to none of the PFCL-assisted group. Conclusion: We reported a statistically significant difference in the intraoperative peeling dynamics of the PFCL-assisted group, accounting for a decreased tendency in the tearing of the ERM flap and possibly reduced damage to the fiber layer, with equal effectiveness in improving visual function and foveal thickness. Full article

Purpose: We investigated intraoperative OCT (iOCT)—guided epiretinal membrane (ERM) and internal limiting membrane (ILM) removal using a novel forceps with a laser-ablated tip surface; it was designed to help prevent indentation force, shear stress, or tractional trauma when grasping very fine membranes. Patients and Methods: This retrospective study included patients who underwent 23- and 25-gauge pars plana vitrectomy (PPV) for vitreoretinal interface disorders. ERM and ILM peeling was performed under guidance with microscope-integrated iOCT using novel ILM forceps with laser-ablated tip surfaces. These forceps were engineered to enhance friction when grasping tissue. Evaluation of ERM/ILM manipulation included postoperative slow-motion video analysis of the number of grasping attempts, initial ILM mobilization, and observed damage to retinal tissue. Results: ERM/ILM removal was successfully performed in all patients, with an average of four grasp actions to initial membrane mobilization (91%). Additional use of a diamond-dusted membrane scraper was used in two cases (9%). Mean best-recorded visual acuity (BRVA) logMAR improved from 0.5 ± 0.34 to 0.33 ± 0.36 (p = 0.05) and mean central retinal thickness (CRT) improved from 462 ± 146 µm to 359 ± 78 µm (p = 0.002). Postoperative iOCT video analysis demonstrated hyper-reflectivity of the inner retinal layers associated with retinal hemorrhage in five eyes (22%), but no grasping-related retinal breaks. Conclusions: The texturized surface on the tips of the ILM forceps were found to be helpful for mobilizing ILM edges from the retinal surface. iOCT-guided ERM surgery also allowed for improved intraoperative tissue visualization. We believe that these two technologies helped reduce both unnecessary surgical maneuvers and retinal damage. Full article

Idiopathic epiretinal membranes (iERMs) are fibrocellular sheets of tissue that develop at the vitreoretinal interface. The iERMs consist of cells and an extracellular matrix (ECM) formed by a complex array of structural proteins and a large number of proteins that regulate cell–matrix interaction, matrix deposition and remodelling. Many components of the ECM tend to produce a layered pattern that can influence the tractional properties of the membranes. We applied a bioinformatics approach on a list of proteins previously identified with an MS-based proteomic analysis on samples of iERM to report the interactome of some key proteins. The performed pathway analysis highlights interactions occurring among ECM molecules, their cell receptors and intra- or extracellular proteins that may play a role in matrix biology in this special context. In particular, integrin β1, cathepsin B, epidermal growth factor receptor, protein-glutamine gamma-glutamyltransferase 2 and prolow-density lipoprotein receptor-related protein 1 are key hubs in the outlined protein–protein cross-talks. A section on the biomarkers that can be found in the vitreous humor of patients affected by iERM and that can modulate matrix deposition is also presented. Finally, translational medicine in iERM treatment has been summed up taking stock of the techniques that have been proposed for pharmacologic vitreolysis. Full article

Purpose: To characterize vitreous humor (VH) exosomes and to explore their role in the development of proliferative vitreoretinopathy (PVR) using mass spectrometry-based proteome profiling. Methods: Exosomes were isolated from undiluted VH from patients with retinal detachment (RD) with various stages of PVR (n = 9), macular hole (MH; n = 5), or epiretinal membrane (ERM; n = 5) using differential ultracentrifugation. The exosomal size, morphology, and exosome markers were analyzed using a nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and an exosome detection antibody array. The tryptic fragment sequencing of exosome-contained proteins was performed using liquid chromatography–tandem mass spectrometry (LC-MS/MS) and a Thermo Lumos Fusion Tribrid Orbitrap mass spectrometer. The pathway analysis of the MS data was performed. Results: The number of exosome particles were significantly increased only in the RD with severe PVR group compared with the control groups and the RD without PVR or with mild PVR groups. Of 724 exosome proteins identified, 382 were differentially expressed (DE) and 176 were uniquely present in PVR. Both DE proteins and exosome proteins that were only present in PVR were enriched in proteins associated with previously known key pathways related to PVR development, including reactive retinal gliosis, pathologic cellular proliferation, inflammation, growth of connective tissues, and epithelial mesenchymal transition (EMT). The SPP1, CLU, VCAN, COL2A1, and SEMA7A that are significantly upregulated in PVR were related to the tissue remodeling. Conclusions: Exosomes may play a key role in mediating tissue remodeling along with a complex set of pathways involved in PVR development. Full article

The epiretinal membrane is a thin sheet of fibrous tissue that can form over the macular area of the retina, and may result in the loss of visual acuity or metamorphopsia, due to superficial retinal folds. A vitrectomy surgery, the current treatment procedure for this pathology, is only performed after symptoms are present. However, sometimes the patients do not present any vision improvements after the surgery. The use of computational methods for a patient-specific biomechanical analysis can contribute to better understanding the mechanisms behind the success or failure of a vitrectomy. Using medical data from two patients who underwent a vitrectomy, one with substantial improvements and another with no improvements, an analysis of the retinal displacement due to the contraction of the epiretinal membrane was performed. Our results suggest a causal effect between the magnitude of the retinal displacements caused by the epiretinal membrane contraction and the outcome of the vitrectomy procedure. Full article

The Epiretinal Membrane (ERM) is an ocular disease that appears as a fibro-cellular layer of tissue over the retina, specifically, over the Inner Limiting Membrane (ILM). It causes vision blurring and distortion, and its presence can be indicative of other ocular pathologies, such as diabetic macular edema. The ERM diagnosis is usually performed by visually inspecting Optical Coherence Tomography (OCT) images, a manual process which is tiresome and prone to subjectivity. In this work, we present a methodology for the automatic segmentation and visualisation of the ERM in OCT volumes using deep learning. By employing a Densely Connected Convolutional Network, every pixel in the ILM can be classified into either healthy or pathological. Thus, a segmentation of the region susceptible to ERM appearance can be produced. This methodology also produces an intuitive colour map representation of the ERM presence over a visualisation of the eye fundus created from the OCT volume. In a series of representative experiments conducted to evaluate this methodology, it achieved a Dice score of $0.826\pm 0.112$ and a Jaccard index of $0.714\pm 0.155$. The results that were obtained demonstrate the competitive performance of the proposed methodology when compared to other works in the state of the art. Full article

We previously reported that the bursa premacularis (BPM), a peculiar vitreous structure located above the macula, contains numerous cells expressing markers of lymphatic endothelial cells, such as podoplanin and LYVE-1. Herein, we examined the expression of lymphatic markers in the Berger’s space (BS), BPM, and vitreous core (VC). BS, BPM, and VC specimens were selectively collected in macular hole and epiretinal membrane patients during vitrectomy and were then immunostained with antibodies for podoplanin, LYVE-1, and fibrillin-1 and -2. By visualization using triamcinolone acetonide, the BS was recognized as a sac-like structure with a septum located behind the lens as well as BPM. Those tissues adhered to the lens or retina in a circular manner by means of a ligament-like structure. Immunostaining showed intense expression of podoplanin and LYVE-1 in the BS. Both BS and BPM stained strongly positive for fibrillin-1 and -2. The VC was faintly stained with antibodies for those lymph-node markers. Our findings indicate that both BS and BPM possibly belong to the lymphatic system, such as lymph nodes, draining excess fluid and waste products into lymphatic vessels in the dura mater of the optic nerve and the ciliary body, respectively, via intravitreal canals. Full article

Background: Idiopathic epiretinal membrane (iERM) is a common eye disease, which can be treated by surgical removal of the fibrotic tissue. Morphological outcome is generally evaluated by optical coherence tomography (OCT). Here, we investigate the impact of surgery on hemodynamics of the posterior pole, using OCT angiography (OCTA). Methods: Patients with unilateral iERM and indication for treatment were included. OCT and OCTA images of the posterior pole were obtained preoperatively and 3-months after 23G vitrectomy with membrane peeling. Parameters of interest included full retinal perfusion, choriocapillaris perfusion (CCP), Sattler’s layer perfusion (SLP), and Haller’s layer perfusion, which were evaluated longitudinally and also compared to unaffected fellow eyes. Using these parameters, multiple regression analyses were used to predict visual outcomes. Results: Sixty-three iERM eyes were recruited, which initially showed a significant bigger central retinal thickness (p < 0.001) and total macular volume (TMV) (p < 0.001) compared to fellow eyes, while perfusion parameters were alike. Three months later, treated eyes had a statistically significant thicker subfoveal choroid (p = 0.006) and showed an increase of CCP (p = 0.003), while SLP decreased (p = 0.014). Lower preoperative TMV and higher SLP were associated with better postoperative visual outcome. Conclusion: In this OCTA study, iERM itself does not affect the choroidal circulation. However, preoperative choroidal circulation will be a biomarker to know the influence on the choroidal circulation after ERM surgery and may be considered as a predictor for visual outcome. Full article