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Keywords = vitreous surgery

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21 pages, 967 KB  
Review
Vitreous Substitutes in Vitreoretinal Surgery: From Native Vitreous Physiology to Bioengineered Experimental Replacements
by Alessandro Avitabile, Ludovica Cannizzaro and Dario Rusciano
J. Funct. Biomater. 2026, 17(6), 301; https://doi.org/10.3390/jfb17060301 - 17 Jun 2026
Viewed by 727
Abstract
The vitreous body is not only a transparent filling material of the posterior segment; it is a soft, hydrated, and biologically active matrix that supports structural, optical, and biochemical homeostasis. Vitrectomy therefore leaves a functional deficit that current substitutes only partly address. Intraocular [...] Read more.
The vitreous body is not only a transparent filling material of the posterior segment; it is a soft, hydrated, and biologically active matrix that supports structural, optical, and biochemical homeostasis. Vitrectomy therefore leaves a functional deficit that current substitutes only partly address. Intraocular gases, silicone oils, and perfluorocarbon liquids remain essential surgical tools, but they mainly provide mechanical tamponade and do not reproduce native viscoelasticity, diffusion control, or protection against oxidative and inflammatory stress. This review considers vitreous replacement as a functional biomaterials challenge. We discuss native vitreous physiology, the limitations of present tamponade agents, and emerging bioengineered substitutes designed to create a more physiological intravitreal environment. Particular attention is given to hydrogel and polymer-based systems, especially hyaluronic acid-based and in situ crosslinked platforms, which are being developed to combine optical clarity, injectability, soft mechanical support, controlled degradation, and favorable tissue interaction. We also emphasize the need for standardized preclinical testing of swelling, enzymatic stability, drug diffusion, rheology, and long-term biocompatibility. Although next-generation materials may move the field beyond passive space filling, manufacturing reproducibility, regulatory validation, chronic safety, and cautious early-phase trials remain major translational barriers. Full article
(This article belongs to the Special Issue Biomedical Applications of Hydrogels: Current Status and Advances)
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13 pages, 9279 KB  
Article
Impact of Posterior Vitreous Detachment on Long-Term Functional and Morphological Retinal Status in Patients After Surgical Epiretinal Membrane Removal
by Alicja Ziontkowska-Wrzałek, Michał Dobrzycki and Anna Machalińska
J. Clin. Med. 2026, 15(10), 3940; https://doi.org/10.3390/jcm15103940 - 20 May 2026
Viewed by 307
Abstract
Background/Objectives: Posterior vitreous detachment (PVD), which is closely related to epiretinal membrane (ERM) formation, can affect macular microstructure and function through persistent tractional forces. The aim of this study was to evaluate whether PVD status influences preoperative characteristics and long-term functional and morphological [...] Read more.
Background/Objectives: Posterior vitreous detachment (PVD), which is closely related to epiretinal membrane (ERM) formation, can affect macular microstructure and function through persistent tractional forces. The aim of this study was to evaluate whether PVD status influences preoperative characteristics and long-term functional and morphological retinal outcomes after ERM surgery. Methods: Ninety patients who underwent idiopathic ERM removal were included and divided into two groups on the basis of intraoperative vitreous status: incomplete or complete PVD. Visual function, retinal imaging, microperimetry, and multifocal electroretinography (mfERG) data were assessed preoperatively and at 1, 4, and 12 months postoperatively. Results: At baseline, compared with the incomplete PVD group, the complete PVD group demonstrated greater fixation stability and lower variability, along with smaller foveal avascular zone (FAZ) areas in both superficial and deep vascular complexes. In terms of absolute postoperative values, the complete PVD group exhibited superior functional outcomes, including higher macular sensitivity and improved fixation variability parameters at 12 months. Morphologically, the incomplete PVD group showed consistently larger FAZ areas in both superficial and deep vascular complexes. In terms of changes from baseline, best-corrected visual acuity (BCVA) gain was greater in the complete PVD group at 1 and 4 months, with no difference at 12 months, whereas no significant between-group differences were observed for other functional or morphological parameters at any time point. Conclusions: Complete PVD is associated with faster visual recovery. Incomplete PVD may induce alterations at the retinal microcirculation level that persist postoperatively and influence microperimetric scores. Full article
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9 pages, 207 KB  
Article
Risk Factors for Postoperative Hyphema Following Baerveldt Glaucoma Implant Surgery: A Retrospective Cohort Study
by Kentaro Iwasaki, Ayami Katsuo, Shogo Arimura, Yoshihiro Takamura and Masaru Inatani
J. Clin. Med. 2026, 15(6), 2247; https://doi.org/10.3390/jcm15062247 - 16 Mar 2026
Cited by 3 | Viewed by 524
Abstract
Background/Objectives: To investigate the incidence and risk factors for postoperative hyphema following Baerveldt glaucoma implant (BGI) surgery. Methods: This retrospective study included Japanese patients who underwent BGI surgery at Fukui University Hospital between 1 April 2012 and 31 March 2025. Hyphema [...] Read more.
Background/Objectives: To investigate the incidence and risk factors for postoperative hyphema following Baerveldt glaucoma implant (BGI) surgery. Methods: This retrospective study included Japanese patients who underwent BGI surgery at Fukui University Hospital between 1 April 2012 and 31 March 2025. Hyphema was defined as any clinically detectable blood in the anterior chamber. Baseline demographic, ocular, and surgical variables were compared between eyes with and without hyphema. Independent risk factors for hyphema were determined using multivariable logistic regression analysis. Results: Of 273 eyes, 77 (28.2%) developed postoperative hyphema. On multivariable analysis, tube insertion site and intraocular pressure (IOP) on postoperative day 1 were identified as independent predictors. Although the overall effect of tube insertion site was borderline (p = 0.074), anterior chamber (odds ratio [OR], 2.83; p = 0.036) and ciliary sulcus insertion (OR, 2.88; p = 0.031) were associated with significantly higher risk of hyphema compared with vitreous cavity insertion. Lower postoperative day 1 IOP was also a significant predictor (p < 0.01). Patient-related factors, including age, diabetes mellitus, hypertension, antithrombotic therapy, neovascular glaucoma (NVG), combined surgery, number of previous intraocular surgeries, and preoperative IOP, were not independently associated with hyphema. In a sensitivity analysis excluding NVG eyes (n = 191), vitreous cavity insertion remained protective, and postoperative day 1 IOP remained an independent predictor. Conclusions: Postoperative hyphema following BGI surgery is primarily determined by surgical factors and early postoperative IOP. Vitreous cavity tube insertion is associated with a markedly lower hyphema risk than anterior chamber or ciliary sulcus insertion. Full article
(This article belongs to the Section Ophthalmology)
28 pages, 3292 KB  
Review
Hydrogels as Promising Carriers for Ophthalmic Disease Treatment: A Comprehensive Review
by Wenxiang Zhu, Mingfang Xia, Yahui He, Qiuling Huang, Zhimin Liao, Xiaobo Wang, Xiaoyu Zhou and Xuanchu Duan
Gels 2026, 12(2), 105; https://doi.org/10.3390/gels12020105 - 27 Jan 2026
Cited by 4 | Viewed by 2226
Abstract
Ocular disorders such as keratitis, glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and dry eye disease (DED) are highly prevalent worldwide and remain major causes of visual impairment and blindness. Conventional therapeutic approaches for ocular diseases, such as eye drops, surgery, and [...] Read more.
Ocular disorders such as keratitis, glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and dry eye disease (DED) are highly prevalent worldwide and remain major causes of visual impairment and blindness. Conventional therapeutic approaches for ocular diseases, such as eye drops, surgery, and laser therapy, are frequently hampered by limited drug bioavailability, rapid clearance, and treatment-related complications, primarily due to the eye’s unique anatomical and physiological barriers. Hydrogels, characterized by their three-dimensional network structure, high water content, excellent biocompatibility, and tunable physicochemical properties, have emerged as promising platforms for ophthalmic drug delivery. This review summarizes the classification, fabrication strategies, and essential properties of hydrogels, and highlights recent advances in their application to ocular diseases, including keratitis management, corneal wound repair, intraocular pressure regulation and neuroprotection in glaucoma, sustained drug delivery for AMD and DR, vitreous substitutes for retinal detachment, and therapies for DED. In particular, we highlight recent advances in stimuli-responsive hydrogels that enable spatiotemporally controlled drug release in response to ocular cues such as temperature, pH, redox state, and enzyme activity, thereby enhancing therapeutic precision and efficacy. Furthermore, this review critically evaluates translational aspects, including long-term ocular safety, clinical feasibility, manufacturing scalability, and regulatory challenges, which are often underrepresented in existing reviews. By integrating material science, ocular pathology, and translational considerations, this review aims to provide a comprehensive framework for the rational design of next-generation hydrogel systems and to facilitate their clinical translation in ophthalmic therapy. Full article
(This article belongs to the Special Issue Novel Hydrogels for Drug Delivery and Regenerative Medicine)
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13 pages, 664 KB  
Article
Ultrasound-Based Assessment of Posterior Vitreous Detachment in Healthy Eyes: Clinical and Biometric Factors Associated with More Advanced PVD
by Cristina Rodriguez-Vidal, Nerea M. Alday, María José Blanco Teijeiro and Manuel Bande
J. Clin. Med. 2025, 14(23), 8587; https://doi.org/10.3390/jcm14238587 - 4 Dec 2025
Viewed by 1411
Abstract
Background/Objectives: Posterior vitreous detachment (PVD) is an age-related physiological process, yet the clinical and biometric factors influencing its progression remain incompletely characterized in adults undergoing routine ophthalmic evaluation at a tertiary center. Characterizing expected vitreous patterns is essential for interpreting vitreoretinal interface [...] Read more.
Background/Objectives: Posterior vitreous detachment (PVD) is an age-related physiological process, yet the clinical and biometric factors influencing its progression remain incompletely characterized in adults undergoing routine ophthalmic evaluation at a tertiary center. Characterizing expected vitreous patterns is essential for interpreting vitreoretinal interface changes in disease. This study aimed to identify independent clinical and biometric factors associated with more advanced PVD stages in adults without macular pathology. Methods: In this cross-sectional observational study, 340 eyes from 198 consecutive adults undergoing routine ophthalmological evaluation at a tertiary hospital (March 2022–April 2023) were analyzed. Eyes with current or past macular disease were excluded. Demographic variables, systemic comorbidities and ocular history were recorded. Axial length was measured using optical biometry IOLMaster 700 (Carl Zeiss Meditec, Jena, Germany). Vitreous status was assessed with 10-MHz B-scan ultrasonography and classified as no PVD, partial PVD or complete PVD. Analyses were performed at the eye level. Given its cross-sectional design, this study evaluates associations and cannot establish causal relationships. Bivariate comparisons examined associations between clinical variables and PVD grade. Multivariable modeling was conducted using a clustered generalized estimating equations (GEE) ordinal logit model as the primary analysis, and a secondary independent-eye ordinal logistic regression model was used to evaluate the proportional-odds assumption and model robustness. Results: Mean age was 55.6 ± 18.3 years, and 68.5% of eyes were from female participants. No PVD, partial PVD and complete PVD were present in 30.9%, 43.5% and 25.6% of eyes, respectively. In the primary GEE model, axial length (OR 1.35; p < 0.001), systemic hypertension (OR 7.13; p < 0.001), and prior cataract surgery (OR 2.13; p = 0.020) were independently associated with more advanced PVD stages. Age showed a modest but significant association with increasing PVD severity (OR 1.03; p = 0.012). Sex and diabetes mellitus were not associated with PVD grade. The independent-eye ordinal model yielded consistent effect directions. Conclusions: In adults without macular disease, more advanced PVD stages are independently associated with axial elongation, systemic hypertension, and previous cataract surgery, while age shows a mild but significant association. These findings provide clinically useful contextual reference information for interpreting vitreoretinal interface changes in health and disease. These associations should not be interpreted as causal due to the cross-sectional nature of the study. Full article
(This article belongs to the Section Ophthalmology)
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12 pages, 3921 KB  
Protocol
High-Dimensional Immune Profiling of Human Retinal Detachment Samples Using Spectral Flow Cytometry: A Protocol for Intraocular Immunotyping
by Laura Molinero-Sicilia, Alejandro G. del Hierro, Nadia Galindo-Cabello, Pablo Redruello-Guerrero, Salvador Pastor-Idoate, Ricardo Usategui-Martín and David Bernardo
Methods Protoc. 2025, 8(6), 141; https://doi.org/10.3390/mps8060141 - 20 Nov 2025
Viewed by 1472
Abstract
Retinal detachment (RD) disrupts the eye’s immune-privileged status, causing a local inflammatory response that contributes to adverse clinical outcomes, including proliferative vitreoretinopathy and suboptimal visual recovery. Comprehensive profiling of intraocular immune cells will offer mechanistic insights and support the development of personalized immunomodulatory [...] Read more.
Retinal detachment (RD) disrupts the eye’s immune-privileged status, causing a local inflammatory response that contributes to adverse clinical outcomes, including proliferative vitreoretinopathy and suboptimal visual recovery. Comprehensive profiling of intraocular immune cells will offer mechanistic insights and support the development of personalized immunomodulatory strategies. Here, we describe a robust and standardized protocol for the collection and high-dimensional analysis of the intraocular immune infiltrate from patients undergoing RD surgery, using state-of-the-art spectral cytometry. Vitreous and retinal tissue samples were obtained during standard surgical procedures, without the need for additional invasive interventions. Our approach integrates two complementary protocols: one that enables selective isolation of immune cells by sorting for CD45+ populations, and a second one that applies a 39-color spectral cytometry panel to profile the general landscape of immune subpopulations. The panel can identify up to 62 distinct viable immune subsets per sample, along with their functional status, as it includes expression of 13 functional markers. Hence, we hereby detail sample preparation, staining, and acquisition workflow, as well as the gating strategy and essential steps necessary for reproducible immunophenotyping. Our protocol, which enables high-dimensional immune profiling from minimal biological material, provides a valuable platform for studying ocular inflammation in RD and other retinal diseases. Full article
(This article belongs to the Section Molecular and Cellular Biology)
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13 pages, 374 KB  
Article
Anatomical and Functional Outcomes of Sutureless Scleral-Fixated Carlevale Intraocular Lens Implantation: A Retrospective Study
by Adam Słoka, Tomasz Chorągiewicz, Karolina Urbańska, Piotr Więsyk, Marcin Woźniak, Joanna Dolar-Szczasny, Mariusz Spyra, Katarzyna Nowomiejska, Mario Damiano Toro and Robert Rejdak
J. Clin. Med. 2025, 14(20), 7309; https://doi.org/10.3390/jcm14207309 - 16 Oct 2025
Cited by 1 | Viewed by 1347
Abstract
Background/Objectives: The purpose of this study was evaluation of the efficacy and the rate of complication of a foldable sutureless scleral-fixated intraocular lens (SSF-IOL), named Carlevale IOL, for the treatment of aphakia without sufficient capsular support due to trauma or complicated cataract [...] Read more.
Background/Objectives: The purpose of this study was evaluation of the efficacy and the rate of complication of a foldable sutureless scleral-fixated intraocular lens (SSF-IOL), named Carlevale IOL, for the treatment of aphakia without sufficient capsular support due to trauma or complicated cataract surgery. Methods: Retrospective, consecutive interventional case series. All consecutive eyes with secondary implantation of aphakic SSF-IOL were considered. The primary outcomes were as follows: best corrected visual acuity (BCVA), refractive error (RE), and intraocular pressure (IOP). Secondary outcome was the occurrence of intraoperative and postoperative complications. Results: SSF-IOL was performed in 21 eyes of 21 patients (7 men and 14 women) with mean age of 74 years (range from 36 to 90 years). The mean follow-up time was 11.4 months. VA improved significantly (p = 0.0007) from 0.38 logMAR at baseline to 0.11 logMAR at the final follow-up. BCVA improved in 18 patients, remained equal in 2 cases, and worsened in 1 case. Mean postoperative RE was −0.83 Diopters (D) (Median = −0.50 D, SD = 1.05 D) and it was less than 1D in 61.9% of patients. Mean IOP at the end of the follow-up was 15.78 mmHg (ranged from 10 to 22 mmHg, SD = 3.65). In one patient a vitreous hemorrhage was observed intraoperatively, but it resolved spontaneously. Postoperative complications included one case of cystoid macular edema and one case of epiretinal membrane. Conclusions: Carlevale SSF-IOL implantation seems to be an effective and safe procedure, ensuring good visual outcomes with a low rate of complication in eyes indicated for secondary IOL implantation. Full article
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28 pages, 678 KB  
Systematic Review
OCTA Biomarkers Underlying Structure–Function Correlations in Idiopathic Epiretinal Membrane: A Systematic Review
by Anca Mădălina Sere, George Adrian Muntean, Andreea Petra Cristea and Simona Delia Nicoară
Diagnostics 2025, 15(20), 2596; https://doi.org/10.3390/diagnostics15202596 - 15 Oct 2025
Cited by 1 | Viewed by 1733
Abstract
Background: Idiopathic epiretinal membrane (iERM) is a common retinal pathology in elderly patients, thought to originate primarily from an anomalous process of posterior vitreous detachment. The standard treatment is pars plana vitrectomy (PPV) with membrane peeling. No consensus exists regarding the optimal timing [...] Read more.
Background: Idiopathic epiretinal membrane (iERM) is a common retinal pathology in elderly patients, thought to originate primarily from an anomalous process of posterior vitreous detachment. The standard treatment is pars plana vitrectomy (PPV) with membrane peeling. No consensus exists regarding the optimal timing of surgery, nor is it clear which patients are most likely to benefit. Given that iERM profoundly affects retinal vascular morphology and function, optical coherence tomography angiography (OCTA) has emerged as a valuable tool for identifying potential biomarkers. This systematic review aimed to synthesize the available evidence on OCTA-derived biomarkers and their correlations with visual function before and/or after surgical intervention in iERM, with a particular focus on their prognostic value for postoperative outcomes. Methods: A systematic search of PubMed/MEDLINE and Scopus was conducted on the 20th of May 2025 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies included patients with iERM undergoing vitreoretinal surgery, used OCTA for pre- and/or postoperative assessment, investigated structure–function correlations, and were designed as clinical trials, observational studies, or case series with more than 10 patients. Exclusion criteria were studies with ≤10 cases, absence of separate iERM analysis, lack of surgical intervention, or non-English language. Data extraction covered study design, demographics, surgical approach, OCTA device, follow-up, OCTA biomarkers, and structure–function outcomes. Risk of bias in observational studies was assessed using the National Institute of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results: The search yielded 1053 records, of which 71 underwent full-text review and 43 met eligibility criteria. All included studies were observational, encompassing 1958 eyes from 1953 patients. The most frequently investigated biomarkers were the foveal avascular zone (FAZ) area and related parameters, vessel density (VD), and foveal density 300 (FD-300). Additional studies evaluated average vessel length (VL), blood flow area, vessel length density (VLD), vessel tortuosity (VT), fractal dimension (FD), and perfusion capacity (PC). Conclusions: By consolidating current evidence, this systematic review provides a comprehensive overview of structure–function correlations in iERM and highlights the potential of OCTA-derived metrics as biomarkers of disease severity and surgical prognosis. These findings help clarify underlying mechanisms of visual decline and establish the context for further research. Nonetheless, interpretation is limited by the observational design of all included studies and by heterogeneity in OCTA methodology and nomenclature, underscoring the need for standardization to improve comparability and foster greater coherence across studies. No funding was provided for this review. Full article
(This article belongs to the Special Issue Optical Coherence Tomography in Diagnosis of Ophthalmology Disease)
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34 pages, 3132 KB  
Review
Innovative Applications of Hydrogels in Contemporary Medicine
by Maciej Rybicki, Karolina Czajkowska, Agata Grochowska, Bartłomiej Białas, Michał Dziatosz, Igor Karolczak, Julia Kot, Radosław Aleksander Wach and Karol Kamil Kłosiński
Gels 2025, 11(10), 798; https://doi.org/10.3390/gels11100798 - 3 Oct 2025
Cited by 11 | Viewed by 5291
Abstract
Hydrogels are hydrophilic, soft polymer networks with high water content and mechanical properties that are tunable; they are also biocompatible. Therefore, as biomaterials, they are of interest to modern medicine. In this review, the main applications of hydrogels in essential clinical applications are [...] Read more.
Hydrogels are hydrophilic, soft polymer networks with high water content and mechanical properties that are tunable; they are also biocompatible. Therefore, as biomaterials, they are of interest to modern medicine. In this review, the main applications of hydrogels in essential clinical applications are discussed. Chemical, physical, or hybrid crosslinking of either synthetic or natural polymers allow for the precise control of hydrogels’ physicochemical properties and their specific characteristics for certain applications, such as stimuli-responsiveness, drug retention and release, and biodegradability. Hydrogels are employed in gynecology to regenerate the endometrium, treat infections, and prevent pregnancy. They show promise in cardiology in myocardial infarction therapy through injectable scaffolds, patches in the heart, and medication delivery. In rheumatoid arthritis, hydrogels act as drug delivery systems, lubricants, scaffolds, and immunomodulators, ensuring effective local treatment. They are being developed, among other applications, as antimicrobial coatings for stents and radiotherapy barriers for urology. Ophthalmology benefits from the use of hydrogels in contact lenses, corneal bandages, and vitreous implants. They are used as materials for chemoembolization, tumor models, and drug delivery devices in cancer therapy, with wafers of Gliadel presently used in clinics. Applications in abdominal surgery include hydrogel-coated meshes for hernia repair or Janus-type hydrogels to prevent adhesions and aid tissue repair. Results from clinical and preclinical studies illustrate hydrogels’ diversity, though problems remain with mechanical stability, long-term safety, and mass production. Hydrogels are, in general, next-generation biomaterials for regenerative medicine, individualized treatment, and new treatment protocols. Full article
(This article belongs to the Special Issue Polymer Hydrogels and Networks)
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30 pages, 2100 KB  
Review
Hydrogel-Based Vitreous Substitutes
by Soheil Sojdeh, Amirhosein Panjipour, Zahra Bibak Bejandi, Majid Salehi, Amal Yaghmour, Zohreh Arabpour, Ali R. Djalilian and R. V. Paul Chan
Int. J. Mol. Sci. 2025, 26(17), 8406; https://doi.org/10.3390/ijms26178406 - 29 Aug 2025
Cited by 9 | Viewed by 3902
Abstract
Hydrogel-based vitreous substitutes have been considered as a potential solution for the treatment of retinal disorders, especially when the natural vitreous body is damaged due to trauma, disease, or surgery. With their high-water content, biocompatibility, and tunable mechanical properties, these hydrogels offer a [...] Read more.
Hydrogel-based vitreous substitutes have been considered as a potential solution for the treatment of retinal disorders, especially when the natural vitreous body is damaged due to trauma, disease, or surgery. With their high-water content, biocompatibility, and tunable mechanical properties, these hydrogels offer a promising alternative to traditional vitreous substitutes. This review explores the role of polymers and crosslinkers in the development of hydrogel-based substitutes, focusing on how these components contribute to the structure and function of hydrogels. The choice of natural polymers, such as hyaluronic acid and collagen, or synthetic ones, such as polyethylene glycol and polyvinyl alcohol, is crucial to mimic the transparency and flexibility of the vitreous body. Crosslinking methods, including physical, chemical, and enzymatic approaches, help control the gelation process and enhance the mechanical strength of the hydrogel. Furthermore, this review demonstrates how these hydrogels interact with biological tissues, which enhances biocompatibility, cell growth, and tissue repair. This review also discusses the challenges and future directions in improving these hydrogels, particularly in terms of long-term stability, integration with ocular tissues, and appropriate mechanical properties. Overall, hydrogel-based vitreous substitutes have significant potential to improve surgical outcomes and restore vision for patients with vitreous injury. Full article
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21 pages, 2145 KB  
Article
Ceruloplasmin and Ferritin Changes in Ocular Fluids from Patients with Vitreoretinal Diseases: Relation with Neuroinflammation and Drusen Formation
by Graziana Esposito, Pamela Cosimi, Bijorn Omar Balzamino, Marisa Bruno, Rosanna Squitti, Lucia Dinice, Fabio Scarinci, Mauro Ciro Antonio Rongioletti, Andrea Cacciamani and Alessandra Micera
Int. J. Mol. Sci. 2025, 26(13), 6307; https://doi.org/10.3390/ijms26136307 - 30 Jun 2025
Viewed by 1427
Abstract
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 [...] Read more.
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
(This article belongs to the Section Molecular Biology)
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10 pages, 937 KB  
Article
Screening Blood and Vitreous for Biomarkers Associated with Proliferative Diabetic Retinopathy
by Stephen Richard, Rawan Kharouba, Jawad Abu-dbai, Oksana Gagarin, Assaf Kratz, Basel Obied, Alon Zahavi and Nitza Goldenberg-Cohen
Diagnostics 2025, 15(11), 1344; https://doi.org/10.3390/diagnostics15111344 - 27 May 2025
Cited by 3 | Viewed by 1540
Abstract
Background/Objectives: Uncontrolled or long-standing diabetes can lead to proliferative diabetic retinopathy (PDR), a condition that significantly impairs vision. A subset of patients does not respond adequately to conventional therapies, such as intravitreal injections of anti-vascular endothelial growth factor (VEGF) or laser treatment. [...] Read more.
Background/Objectives: Uncontrolled or long-standing diabetes can lead to proliferative diabetic retinopathy (PDR), a condition that significantly impairs vision. A subset of patients does not respond adequately to conventional therapies, such as intravitreal injections of anti-vascular endothelial growth factor (VEGF) or laser treatment. This study aims to identify potential biomarkers for alternative treatment pathways in the vitreous and blood of patients with severe PDR. Methods: Vitreous samples were collected from PDR patients (n = 3) undergoing vitrectomy for vitreous hemorrhage and from control patients (n = 9) undergoing ocular surgery for epiretinal membrane or macular holes. Blood samples were collected from a separate group of PDR patients (n = 13) and non-diabetic control patients without retinopathy (n = 13). Medical histories were obtained. Two-stage real-time quantitative polymerase chain reaction (qPCR) was used to evaluate mRNA expression levels of genes potentially implicated in PDR, including HIF2A, PAI-1, TIE1, TIE2, ANGPT2, and VEGFA. Molecular and statistical analyses were performed to compare PDR and control vitreous and blood samples. Results: The PDR vitrectomy group included two females and one male, aged 71–77 years (mean 74 years). All participants had undergone pan-retinal photocoagulation and two had received anti-VEGF injections before vitrectomy. These participants had elevated HbA1c levels. Targeted vitreous gene analysis revealed varying levels of increased expression of all genes examined as compared to the control group. A trend for increased median expression was demonstrated for all examined genes: HIF2A by 1.44-fold (PDR = 2.50, control = 1.74, p = 0.21), PAI-1 by 1.56-fold (PDR = 3.00, control = 1.93, p = 0.37), TIE1 by 1.36-fold (PDR = 2.33, control = 1.72, p = 0.66), TIE2 by 2.06-fold (PDR = 2.81, control = 1.36, p = 0.51), ANGPT2 by 2.93-fold (PDR = 6.32, control = 2.16, p = 0.1), and VEGFA by 3.53-fold (PDR = 3.51, control = 0.99, p = 0.08). PDR blood sample analysis as compared to controls showed a trend for increased expression of VEGFA by 1.2-fold (PDR = 0.88, control = 0.74, p = 0.57), whereas the other examined genes showed a trend of reduced expression; HIF2A decreased by 0.50-fold (PDR = 0.38, control = 0.75, p = 0.07), PAI by 0.51-fold (PDR = 0.35, control = 0.69, p = 0.09), TIE-1 by 0.79-fold (PDR = 0.79, control = 1.00, p = 0.54), TIE-2 by 0.70-fold (PDR = 0.58, control = 0.82, p = 0.34), and ANGPT2 by 0.45-fold (PDR = 0.51, control = 1.15, p = 0.11). Conclusions: Vitreous sample analysis revealed a trend of increased mRNA expression of ANGPT2 and VEGFA in patients with PDR. Blood sample analysis did not show a significant increase of VEGFA mRNA expression but a decreased trend of HIF2A, PAI-1, and ANGPT2 mRNA expression. These trends warrant validation in a larger cohort to explore alternative pathways for targeted treatment. Full article
(This article belongs to the Special Issue Diagnosis and Management of Ophthalmic Disorders)
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10 pages, 13929 KB  
Article
Amniotic Membrane Coverage for Intractable Large Macular Holes: A First Report with Japanese Patients
by Yasunari Hayakawa and Takayuki Inada
J. Clin. Med. 2025, 14(11), 3708; https://doi.org/10.3390/jcm14113708 - 26 May 2025
Cited by 2 | Viewed by 1445
Abstract
Background and Objective: In recent years, the success rate of treating refractory macular holes with internal limiting membrane (ILM) inversion has significantly increased. However, closure remains challenging for large macular holes even after ILM inversion. Here, we report the evaluation of amniotic [...] Read more.
Background and Objective: In recent years, the success rate of treating refractory macular holes with internal limiting membrane (ILM) inversion has significantly increased. However, closure remains challenging for large macular holes even after ILM inversion. Here, we report the evaluation of amniotic membrane coverage for intractable large macular holes. Methods: We retrospectively analyzed five eyes of five patients (three males, two females; mean age 70.6 ± 13.3 years) with refractory macular holes that did not close after ILM inversion performed at our institution from June 2022 to May 2024 and were followed up for more than 6 months. Preoperative macular hole dimensions were assessed using optical coherence tomography (OCT). Surgery was performed using 27-gauge transconjunctival vitrectomy without ILM peeling. Two layers of amniotic membrane were placed in the macular center using a double-headed technique under air tamponade, followed by a complete vitreous fluid exchange with 10% sulfur hexafluoride gas. Postoperative outcomes were evaluated using OCT for macular hole closure and visual function assessment 6 months postoperatively. Results: The preoperative macular hole size was 1072.200 ± 189.043 μm, and the preoperative logMAR visual acuity was 1.222 ± 0.278. All macular holes closed postoperatively, with a postoperative logMAR visual acuity of 0.518 ± 0.165. Conclusions: The amniotic membrane coverage technique for intractable large macular holes was found to be an effective method contributing to macular hole closure and visual acuity improvement postoperatively. Full article
(This article belongs to the Special Issue Advancements and Challenges in Retina Surgery)
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10 pages, 2192 KB  
Article
Combined Surgically Induced Macular Detachment and Autologous Internal Limiting Membrane Transplantation for Refractory Full Thickness Macular Hole
by Rino Frisina, Laura Di Leo, Ilenia Gallo Afflitto, Andrea Vulpetti, Lorenzo Motta and Gabriella De Salvo
J. Clin. Med. 2025, 14(6), 2123; https://doi.org/10.3390/jcm14062123 - 20 Mar 2025
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Abstract
Background/Objectives: To propose a combined surgery of surgically induced macular detachment (MD) and autologous internal limiting membrane (ILM) transplantation to treat refractory full thickness macular holes (FTMHs). Methods: A series of patients affected by refractory FTMHs underwent a combined surgery. The [...] Read more.
Background/Objectives: To propose a combined surgery of surgically induced macular detachment (MD) and autologous internal limiting membrane (ILM) transplantation to treat refractory full thickness macular holes (FTMHs). Methods: A series of patients affected by refractory FTMHs underwent a combined surgery. The following demographic and clinical data were collected: age, gender, eye, lens status, and best corrected visual acuity (BCVA). The tomographic pre- and post-operative parameters were the following: pre-operative FTMH diameter, refractory FTMH morphology (flat/with cuff), FTMH closure, foveal profile (regular/flat/inverted), flap displacement, and outer retinal layers restoration. Results: The study included a total of 14 pseudophakic eyes (14 patients). In all of the patients, surgical FTMH closure was reached. The mean BCVA improved after surgery from 1.1 ± 0.14 to 0.48 ± 03 logMAR (p < 0.0001). Statistical analysis demonstrated that the larger the FTMH, the poorer the post-operative gain in BCVA (p −0.5). The post-operative regular foveal profile was obtained in 50% of the eyes with a mean post-operative BCVA of 0.3 logMAR. A negative correlation between the time interval from diagnosis to surgery and post-operative BCVA gain was highlighted (p −0.8). Conclusions: The proposed combined surgical technique led to encouraging anatomical and functional results. Surgically induced MD increased the elasticity of the retina, and the free flap isolated the macular hole from the vitreous chamber favoring its closure. Full article
(This article belongs to the Special Issue Clinical Treatment of Refractory Full Thickness Macular Hole (FTMH))
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10 pages, 868 KB  
Article
Outcomes and Predictive Factors of I-125 Plaque Therapy for Refractory Retinoblastoma
by Yacoub A. Yousef, Farah Halawa, Mona Mohammad, Lama Al-Fahoum, Rama Soudi, Mustafa Mehyar, Reem AlJabari, Hadeel Halalsheh, Ibrahim AlNawaiseh and Imad Jaradat
J. Clin. Med. 2025, 14(5), 1778; https://doi.org/10.3390/jcm14051778 - 6 Mar 2025
Viewed by 2126
Abstract
Objective: This study aimed to evaluate the outcomes and predictive factors of I-125 radioactive plaque therapy for recurrent and refractory retinoblastoma (Rb) cases that failed primary systemic chemotherapy and focal therapies. Methods: A retrospective study of 20 eyes with intraocular Rb [...] Read more.
Objective: This study aimed to evaluate the outcomes and predictive factors of I-125 radioactive plaque therapy for recurrent and refractory retinoblastoma (Rb) cases that failed primary systemic chemotherapy and focal therapies. Methods: A retrospective study of 20 eyes with intraocular Rb treated with I-125 radioactive plaque therapy (Apex dose 45 Gy) from 2013 to 2023 was conducted. Data on tumor characteristics, treatments, and outcomes were collected over a follow-up period of at least one year. Results: There were 11 (55%) males and 8 (40%) patients who had bilateral disease. All 20 treated eyes (100%) showed initial tumor regression, while long-term tumor control and eye salvage were achieved in 14 eyes (70%). Six eyes (30%) experienced uncontrollable tumor recurrence after a mean of 6 months (range: 3–12 months) after plaque therapy. Recurrence included main tumor activity in six eyes and additional resistant vitreous seeds in two of them. Poor predictive factors for eye salvage included Group D at diagnosis (p = 0.044), active vitreous seeds at the time of plaque therapy ((p = 0.045), tumor thickness >5.0 mm (p = 0.045), and tumor base dimension >12 mm (p = 0.023). Post-plaque complications included cataracts in seven eyes (35%), tumor hemorrhage in six eyes (30%), retinal detachment in four eyes (20%), radiation retinopathy in three eyes (15%), and neovascular glaucoma in one eye (5%). Five (83%) of those with tumor hemorrhage had plaque surgery performed within less than 6 months of the last cycle of systemic chemotherapy. At a mean follow-up of 36 months (range: 12–96 months), five eyes (25%) were enucleated, and high-risk pathological features were identified in three eyes, including post-laminar optic nerve infiltration (one eye) and massive choroidal invasion (two eyes). All patients were alive and free of metastasis except one patient (5%) whose parents refused enucleation and came back with extra-scleral extension and bone marrow metastasis and eventually passed away. Conclusions: I-125 radioactive plaque therapy is a valuable salvage treatment for recurrent and refractory retinoblastoma, achieving tumor control and eye salvage in 70% of cases with an acceptable safety profile. However, the observed recurrence rate (30%) at an apex dose of 45 Gy suggests a need for dose optimization and individualized treatment strategies. Identifying high-risk features, such as Group D disease, active vitreous seeds, and larger tumors, is crucial for patient selection and outcome prediction. Future research should explore alternative dosing strategies, combination therapies, and improved predictive models to enhance long-term tumor control while minimizing complications. Full article
(This article belongs to the Section Ophthalmology)
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