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Search Results (528)

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Keywords = age-related eye diseases

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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
Viewed by 48
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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16 pages, 1057 KB  
Article
Combined Therapy Versus Fortified Anti-VEGF Monotherapy in Type C Polypoidal Choroidal Vasculopathy: Long-Term Outcomes and Exploratory Biomarker Insights
by Windsor Wen-Jin Chao, Howard Wen-Haur Chao and Hsiao-Ming Chao
Int. J. Mol. Sci. 2026, 27(3), 1224; https://doi.org/10.3390/ijms27031224 - 26 Jan 2026
Viewed by 92
Abstract
While standard anti- vascular endothelial growth factor (VEGF) therapy, with or without photodynamic therapy (PDT), is effective for patients with polypoidal choroidal vasculopathy (PCV), not all achieve optimal visual outcomes. This study aimed to compare fortified (double the dose and the volume of [...] Read more.
While standard anti- vascular endothelial growth factor (VEGF) therapy, with or without photodynamic therapy (PDT), is effective for patients with polypoidal choroidal vasculopathy (PCV), not all achieve optimal visual outcomes. This study aimed to compare fortified (double the dose and the volume of the standard one) anti-VEGF combined with PDT versus fortified anti-VEGF monotherapy and to investigate biomolecular profiles and disease relationships among PCV, neovascular age-related macular degeneration (nvAMD), and central serous chorioretinopathy (CSCR). The goal was to identify novel pathways to inform future therapeutic strategies, including hypoxia-inducible factors (HIF)-1α inhibitors. This retrospective cohort study included 23 eyes with indocyanine green-confirmed type C PCV. One eye treated with transpupillary thermotherapy was not included in the following two groups. Patients received either combined therapy (PDT + fortified-dose anti-VEGF; n = 12) or fortified-dose anti-VEGF monotherapy (n = 10). Primary outcomes were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Secondary outcomes included injection burden and recurrence. Exploratory analyses examined aqueous biomarkers, including VEGF, placental growth factor (PlGF), β-catenin, HIF-1α, and Wnt1 across PCV, CSCR, and nvAMD to identify novel therapeutic targets. Significant (p = 0.003/p = 0.005) median CRT reduction was similar (p = 0.468) between groups (combined/monotherapy: 137.5 µm/106.5 µm). BCVA (median [Q1, Q3]) change in logarithm of the minimum angle of resolution (LogMAR) was not statistically significant (p = 0.279), with 0.25 [0.00, 0.98] in the combined group versus 0.00 [−0.03, 0.28] in the monotherapy group. Treatment burden of anti-VEGFs per person per year was lower with combined therapy (1.16 ± 0.47# PDT + 2.81 ± 0.92# anti-VEGF injections) compared with monotherapy (4.61 ± 1.49# injections). Six eyes demonstrated recurrence at a mean of 15.5 months. Incomplete regression of polyps and branching vascular networks was observed in all eyes. Exploratory biomarker analysis revealed significantly (p < 0.05) higher VEGF and PlGF levels in nvAMD compared with PCV. nvAMD also demonstrated significantly (p < 0.05) higher β-catenin and lower HIF-1α levels relative to PCV and CSCR, while no significant biomarker differences were observed between PCV and CSCR. Combined therapy or monotherapy with fortified anti-VEGFs reduced treatment burden and achieved significant anatomical improvement but did not yield superior functional outcomes, highlighting the therapeutic difficulty of type C PCV. Biomarker profiling revealed shared hypoxia-related mechanisms between PCV and CSCR, with elevated HIF-1α compared to nvAMD indicating a “preliminary” possible role for HIF-1α inhibitors. Differential expression of these biomarkers highlights additional molecular pathways that may inform future targeted interventions. Full article
(This article belongs to the Special Issue Molecular Insight into Retinal Diseases: 2nd Edition)
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20 pages, 1368 KB  
Review
A Review of Major Compounds in Bilberry (Vaccinium myrtillus L.) Fruits and Leaves: Isolation, Purification, and Their Antiaging Effects
by Jayanta Kumar Patra, Han-Seung Shin and Gitishree Das
Nutrients 2026, 18(2), 350; https://doi.org/10.3390/nu18020350 - 21 Jan 2026
Viewed by 183
Abstract
The bilberry is a low-growing plant native to northern Europe. It belongs to the genus Vaccinium. Bilberry is essential in the local diets of some countries and is used as an herbal medicine to manage several ailments. Still, it is not used for [...] Read more.
The bilberry is a low-growing plant native to northern Europe. It belongs to the genus Vaccinium. Bilberry is essential in the local diets of some countries and is used as an herbal medicine to manage several ailments. Still, it is not used for commercial farming in many countries. It has recently been known as a great source of naturally available bioactive compounds and colorants. Bilberry is a therapeutic fruit acknowledged for its rich flavonoids, anthocyanins, carotenoids, ascorbic acid, phenolic acid, tocopherols, and vitamin content. It is one of the richest sources of natural anthocyanins. The polyphenolic compounds in bilberry provide abundant antioxidant content, which are supposed to be the vital bioactive compounds accountable for various health benefits. Even though bilberry is mostly promoted for eye care or vision improvement. It is also stated to promote antioxidant defense and lower oxidative stress, having antiaging, anti-inflammatory, lipid-lowering, antimicrobial effects, lowering blood glucose and other age-related diseases, etc. Reports suggest that apart from the fruit, the leaves of bilberry are equally rich in numerous bioactive compounds of medicinal importance. This current review offers valuable insights on bilberry fruits, leaves, and extracts, providing an inclusive assessment of their bioactive compound configuration, related biological prospects, and the extraction methodology of their major compounds. This review offers a summary of the existing information on the antiaging potential of bilberry fruits and leaves, and analytically reviews the outcome of clinical trials, with special attention towards its medicinal properties. Full article
(This article belongs to the Special Issue Effects of Diet and Nutrition on Aging and Age-Related Disorders)
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11 pages, 217 KB  
Article
The Effect of Intravitreal Ranibizumab Injection on Retinal Nerve Fiber Layer Thickness and Optic Disc Parameters
by Gülin Tuğba Ongun and Ramazan Yağcı
J. Clin. Med. 2026, 15(2), 449; https://doi.org/10.3390/jcm15020449 - 7 Jan 2026
Viewed by 208
Abstract
Objectives: To evaluate the effects of intravitreal ranibizumab on retinal nerve fiber layer (RNFL) thickness and optic disc parameters in patients treated for exudative age-related macular degeneration (AMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). Methods: This retrospective study analyzed the [...] Read more.
Objectives: To evaluate the effects of intravitreal ranibizumab on retinal nerve fiber layer (RNFL) thickness and optic disc parameters in patients treated for exudative age-related macular degeneration (AMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). Methods: This retrospective study analyzed the clinical records of 60 patients who received intravitreal ranibizumab injections for macular edema secondary to AMD, DME, or RVO between October 2014 and January 2016. All patients received intravitreal ranibizumab at a dose of 0.5 mg. Best-corrected visual acuity (BCVA) and intraocular pressure (IOP) were recorded at baseline and during follow-up. RNFL thickness and optic disc parameters were assessed using optical coherence tomography (OCT) and Heidelberg Retina Tomograph III (HRT-3). Measurements were obtained before treatment and at 1 week, 1 month, 3 months, and 6 months after injection. Comparisons were performed within and between disease groups. Results: Of the 60 patients, 31 (51.7%) had DME, 20 (33.3%) had AMD, and 9 (15.0%) had RVO. Best-corrected visual acuity improved significantly during the follow-up period. Mean RNFL thickness measured by OCT showed a significant reduction in the DME and RVO groups (p = 0.0001 and p = 0.043, respectively). In contrast, no significant changes in RNFL thickness were detected using HRT-3, and no consistent alterations in other optic disc parameters were observed. Changes in optic disc parameters varied among disease groups. Conclusions: Intravitreal ranibizumab treatment was associated with a reduction in mean RNFL thickness measured by OCT in patients with DME and RVO during a six-month follow-up period, whereas no corresponding RNFL thinning was detected using HRT-3 in any disease group. The observed optic disc parameter changes appeared to be disease specific. Given the absence of untreated control eyes and the exclusion of patients with glaucoma, these findings apply only to non-glaucomatous eyes and should not be extrapolated to patients with glaucoma. Further prospective studies with larger cohorts, appropriate control groups, and longer follow-up durations are warranted to clarify the long-term effects of anti-VEGF therapy on the optic nerve. Full article
(This article belongs to the Section Ophthalmology)
18 pages, 603 KB  
Systematic Review
Uncovering Sex and Gender Differences in Sarcoidosis: A Systematic Review of Current Evidence
by Tommaso Pianigiani, Beatrice Perea, Akter Dilroba, Asia Fanella, Clarissa Milli, Sara Postiferi, Leonardo Rubegni, Laura Bergantini, Miriana D’Alessandro, Paolo Cameli and Elena Bargagli
J. Pers. Med. 2026, 16(1), 24; https://doi.org/10.3390/jpm16010024 - 5 Jan 2026
Viewed by 453
Abstract
Introduction: Sarcoidosis is a systemic granulomatous disorder classified among interstitial lung diseases (ILDs). While the lungs and intrathoracic lymph nodes are most affected, the disease can involve multiple organs. The heterogeneity of clinical presentation arises from complex interactions between environmental exposures and immune [...] Read more.
Introduction: Sarcoidosis is a systemic granulomatous disorder classified among interstitial lung diseases (ILDs). While the lungs and intrathoracic lymph nodes are most affected, the disease can involve multiple organs. The heterogeneity of clinical presentation arises from complex interactions between environmental exposures and immune responses in genetically susceptible individuals. Sex-dependent genetic variations are associated with differences in phenotype and organ localization. Gender-related factors also influence the impact of sarcoidosis on quality of life and health perception, contributing to variability in disease burden and outcomes. Aim of the study: to provide an overview of sex- and gender-related differences in sarcoidosis, focusing on pathophysiological and clinical implications. Material and Methods: The systematic search was conducted on Medline database through Pubmed search engine. We included all clinical studies from 1992 to the present, and imposed language restrictions, accepting only English publications. Case reports, reviews, and pre-print studies were excluded. Results: A total of 35 studies were included. Sex differences significantly influenced both age of onset and clinical presentation of the disease. Women received a diagnosis of sarcoidosis at an older age and exhibited more frequently extrapulmonary localizations, with predominant involvement of the eyes, skin, and extra-thoracic lymph nodes. In contrast, men more commonly presented with limited pulmonary forms. Löfgren syndrome was more prevalent among women and appeared to be associated with sex-specific genetic variations, particularly within the MHC region. Gender differences also impacted quality of life and disease perception: women reported a lower quality of life and were more susceptible to anxiety and depression throughout the disease course. Conclusions: This report confirms that clinical presentation of sarcoidosis is significantly influenced by sex and gender. The identification of sex- and gender-specific clinical patterns supports a personalized medicine framework, in which diagnostic assessment, monitoring strategies, and therapeutic approaches may be tailored according to individual biological and gender-related characteristics. Full article
(This article belongs to the Section Personalized Therapy in Clinical Medicine)
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12 pages, 903 KB  
Article
Effects of a Red-Ginger-Based Multi-Nutrient Supplement on Optic Nerve Head Blood Flow in Open-Angle Glaucoma
by Akiko Hanyuda, Satoru Tsuda, Nana Takahashi, Naoki Takahashi, Kota Sato and Toru Nakazawa
Nutrients 2026, 18(1), 140; https://doi.org/10.3390/nu18010140 - 1 Jan 2026
Viewed by 700
Abstract
Objectives: Glaucoma is an age-related neurodegenerative disease, characterized by retinal ganglion cell loss and progressive visual field deterioration. Beyond intraocular pressure (IOP), vascular and metabolic dysregulation contributes to optic nerve head (ONH) ischemia and neuronal vulnerability. Nutritional factors with antioxidative and vasodilatory [...] Read more.
Objectives: Glaucoma is an age-related neurodegenerative disease, characterized by retinal ganglion cell loss and progressive visual field deterioration. Beyond intraocular pressure (IOP), vascular and metabolic dysregulation contributes to optic nerve head (ONH) ischemia and neuronal vulnerability. Nutritional factors with antioxidative and vasodilatory properties may help preserve ocular perfusion. This study investigated the acute and subacute effects of a single dose of a dietary supplement containing red ginger extract (Zingiber officinale var. rubra), lutein, and vitamin B6 on ONH blood flow in patients with open-angle glaucoma (OAG). Methods: A retrospective self-controlled study was conducted at Tohoku University Hospital between August 2023 and March 2025. ONH blood flow was quantified using a laser speckle flowgraphy (LSFG) baseline one hour after and one month after continuous oral supplementation in patients with OAG. Systemic parameters, ocular biometry, and concomitant glaucoma medications were recorded in medical charts. Relative mean blur rate (MBR) changes were analyzed using a linear mixed-effects model, accounting for repeated measures and inter-eye correlations. Results: Nineteen glaucoma patients (38 eyes) were included in the acute phase and 13 patients (26 eyes) completed the one-month follow-up. After adjusting for age and sex, a single oral dose of red ginger extract significantly increased the relative MBR at 1 h (106.9 ± 3.1%; p < 0.05), and this enhancement increased after 1 month of continuous intake (115.4 ± 6.7%; p < 0.05). Greater ONH perfusion was particularly prominent in eyes with shorter axial length. Conclusions: Oral supplementation was associated with acute and short-term increases in ONH blood flow in glaucomatous eyes. Although this study was a retrospective study without a placebo-controlled comparison group, our findings offer hypothesis-generating evidence that nutritional interventions may support ocular perfusion alongside conventional glaucoma management. Future prospective randomized controlled trials are required to confirm these associations. Full article
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13 pages, 3572 KB  
Article
Diagnostic Performance of Ring Aperture Retro Mode Imaging for Detecting Pigment Migration in Age-Related Macular Degeneration
by Thomas Desmettre, Gerardo Ledesma-Gil and Michel Paques
Diagnostics 2026, 16(1), 42; https://doi.org/10.3390/diagnostics16010042 - 23 Dec 2025
Viewed by 350
Abstract
Background/Objectives: Pigment migration is a key biomarker of progression in age-related macular degeneration (AMD). This study assessed the diagnostic performance of ring aperture Retro mode (RAR) imaging for detecting pigment migration and compared its performance with established multimodal imaging techniques. Methods: [...] Read more.
Background/Objectives: Pigment migration is a key biomarker of progression in age-related macular degeneration (AMD). This study assessed the diagnostic performance of ring aperture Retro mode (RAR) imaging for detecting pigment migration and compared its performance with established multimodal imaging techniques. Methods: This retrospective study included 80 eyes from 61 consecutive patients with AMD who underwent multimodal imaging with color fundus images (CFIs), fundus autofluorescence (FAF), RAR imaging (Mirante, NIDEK), and en face optical coherence tomography (OCT) with B-scans (Cirrus HD-OCT 5000, Zeiss). Two independent retina specialists graded the AMD stage and the presence of pigment migration across modalities. Sensitivity and positive predictive value (PPV) of RAR were calculated using en face OCT as the reference standard. Results: RAR demonstrated high diagnostic performance, with a sensitivity of 94.7% and a PPV of 93.4% relative to en face OCT. RAR frequently identified pigment migration that was not visible on CFI or FAF, particularly in early AMD and in eyes with media opacity. Distinct morphologic patterns—including hyperreflective foci, thickened retinal pigment epithelium, refractile drusen, and cuticular drusen—were consistently identifiable on RAR. In four eyes with geographic atrophy, RAR detected perifoveal pigment redistribution at least six months before foveal involvement was confirmed by OCT and FAF. Conclusions: RAR imaging is a rapid, sensitive, and clinically practical technique for detecting pigment migration in AMD. By complementing en face OCT and enhancing visualization in cases where standard imaging is limited, RAR may strengthen early disease surveillance, support prognostic assessment, and improve multimodal diagnostic workflows in routine practice. Full article
(This article belongs to the Special Issue Diagnosis and Management of Ophthalmic Disorders)
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10 pages, 833 KB  
Systematic Review
Laser Speckle Flowgraphy (LSFG) in Age-Related Macular Degeneration and Diabetic Retinopathy: A Systematic Review of Recent Literature
by Carlo Bellucci, Medea Virgili, Alessandra Romano, Salvatore Antonio Tedesco and Paolo Mora
J. Clin. Med. 2025, 14(24), 8928; https://doi.org/10.3390/jcm14248928 - 17 Dec 2025
Viewed by 393
Abstract
Background: Laser Speckle Flowgraphy (LSFG) is a non-invasive imaging technology that quantitatively evaluates retinal and choroidal blood flow by analyzing speckle patterns generated by laser light scattering. This systematic review summarizes the application of LSFG in two major degenerative retinal diseases: age-related [...] Read more.
Background: Laser Speckle Flowgraphy (LSFG) is a non-invasive imaging technology that quantitatively evaluates retinal and choroidal blood flow by analyzing speckle patterns generated by laser light scattering. This systematic review summarizes the application of LSFG in two major degenerative retinal diseases: age-related macular degeneration (AMD) and diabetic retinopathy (DR). Methods: A comprehensive literature search (2010–2025) was conducted in PubMed, Cochrane Library and EMBASE according to PRISMA guidelines. Twenty-three studies including a total of 974 eyes (191 AMD, 783 DR) were analyzed. Results: In AMD, LSFG detected baseline reductions in choroidal and retinal perfusion in non-exudative disease, often extending beyond atrophic regions. Anti-VEGF injections produced acute reductions in MBR, particularly with brolucizumab, with partial recovery over time; drug-specific differences suggest a potential impact on geographic atrophy progression. In DR, LSFG revealed early microvascular dysfunction even in asymptomatic eyes. Retinal and choroidal MBR and blowout score correlated with HbA1c, DR severity, and inflammatory mediators. Intravitreal anti-VEGF therapy consistently reduced retinal and choroidal MBR and RFV, while conventional panretinal photocoagulation decreased choroidal flow and vascular caliber more robustly than patterned laser, reflecting oxygenation-driven VEGF modulation. Low baseline MBR predicted higher central macular thickness and reduced therapeutic response in diabetic macular edema. Conclusions: LSFG provides reproducible, rapid, and non-invasive quantitative insights into ocular hemodynamics across degenerative retinal diseases. Its integration into multimodal imaging may facilitate early diagnosis, support personalized management, and assist in the prognostic assessment of retinal and choroidal vascular disorders. Full article
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21 pages, 361 KB  
Review
Plant-Based Care and Therapy in Ophthalmology
by Olga Klaudia Szewczyk-Roszczenko, Marta Pietruszyńska, Iga Anna Iwańska, Piotr Roszczenko, Krzysztof Bielawski, Agnieszka Gornowicz and Anna Bielawska
Antioxidants 2025, 14(12), 1510; https://doi.org/10.3390/antiox14121510 - 16 Dec 2025
Viewed by 1423
Abstract
Oxidative stress, inflammation, and environmental factors contribute significantly to the development of ocular disorders, including dry eye disease, conjunctivitis, and age-related degenerative changes. In recent years, growing attention has been directed toward natural compounds and plant-derived extracts with potential protective and therapeutic effects [...] Read more.
Oxidative stress, inflammation, and environmental factors contribute significantly to the development of ocular disorders, including dry eye disease, conjunctivitis, and age-related degenerative changes. In recent years, growing attention has been directed toward natural compounds and plant-derived extracts with potential protective and therapeutic effects on eye health. This work provides an overview of selected bioactive substances, such as carotenoids (β-carotene), flavonoids, vitamins C and E, and phytochemicals derived from plants. These agents exhibit antioxidative, anti-inflammatory, antimicrobial, and regenerative properties that may support ocular surface integrity, reduce oxidative damage, and improve visual performance. The integration of such natural remedies into ocular health strategies may offer complementary benefits to conventional therapies. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
20 pages, 2189 KB  
Review
Gravity in the Eye: How ‘Gravitational Ischemia’ in the Retina May Be Released and Resolved Through Rapid Eye Movement (REM), a Component of Gravity Opposition Physiology
by J. Howard Jaster, Joshua Ong and Giulia Ottaviani
Physiologia 2025, 5(4), 55; https://doi.org/10.3390/physiologia5040055 - 12 Dec 2025
Viewed by 505
Abstract
This narrative review of rapid eye movement (REM) focuses on its primary etiology and how it fits into the larger framework of neurophysiology and general physiology. Arterial blood flow in the retina may be sensitive to the full overlying ‘weight’ of its adjacent [...] Read more.
This narrative review of rapid eye movement (REM) focuses on its primary etiology and how it fits into the larger framework of neurophysiology and general physiology. Arterial blood flow in the retina may be sensitive to the full overlying ‘weight’ of its adjacent and contiguous vitreous humor caused by the humoral mass effect in the Earth’s gravitational field. During waking hours of the day, this ‘weight’ is continuously shifted in position due to changing head position and eye movements associated with ordinary environmental observations. This reduces its impact on any one point on the retinal field. However, during sleep, the head may maintain a relatively constant position (often supine), and observational eye movements are minimal, leaving essentially one retinal area exposed at the ‘bottom’ of each eye, relative to gravity. During sleep, REM may provide a mechanism for frequently repositioning the retina with respect to the weight it incurs from its adjacent (overlying) vitreous humor. Our findings were consistent with the intermittent terrestrial nocturnal development of ‘gravitational ischemia’ in the retina, wherein the decreased blood flow is accompanied metabolically by decreased oxygen tension, a critically important metric, with a detrimental influence on nerve-related tissue generally. However, the natural mechanisms for releasing and resolving gravitational ischemia, which likely involve glymphatics and cerebrospinal fluid shifts, as well as REM, may gradually fail in old age. Concurrently associated with old age in some individuals is the deposition of alpha-synuclein and/or tau in the retina, together with similar deposition in the brain, and it is also associated with the development of Parkinson’s disease and/or Alzheimer’s disease, possibly as a maladaptive attempt to release and resolve gravitational ischemia. This suggests that a key metabolic parameter of Parkinson’s disease and Alzheimer’s disease may be a lack of oxygen in some neural tissues. There is some evidence that oxygen therapy (hyperbaric oxygen) may be an effective supplemental treatment. Many of the cardinal features of spaceflight-associated neuro-ocular syndrome (SANS) may potentially be explained as features of gravity opposition physiology, which becomes unopposed by gravity during spaceflight. Gravity opposition physiology may, in fact, create significant challenges for humans involved in long-duration space travel (long-term microgravity). Possible solutions may include the use of artificial gravitational fields in space, such as centrifuges. Full article
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23 pages, 2079 KB  
Review
The Interplay Between the Ubiquitin–Proteasome System and Oxidative Stress: A Future Perspective in Eye Diseases
by Grazia Raffaella Tundo, Gabriele Antonio Zingale, Irene Pandino, Elisa Peroni, Diego Sbardella and Alessio Bocedi
Antioxidants 2025, 14(12), 1475; https://doi.org/10.3390/antiox14121475 - 9 Dec 2025
Viewed by 627
Abstract
Redox unbalance, a molecular trait common to neurodegenerative conditions and para-physiological processes like aging, is a critical factor in disease development and in exacerbating progression. The mechanism by which redox imbalance perturbs cellular homeostasis is strongly linked to the activity and function of [...] Read more.
Redox unbalance, a molecular trait common to neurodegenerative conditions and para-physiological processes like aging, is a critical factor in disease development and in exacerbating progression. The mechanism by which redox imbalance perturbs cellular homeostasis is strongly linked to the activity and function of the ubiquitin–proteasome system (UPS). The UPS, along with autophagy, is the primary intracellular proteolytic system, regulating targeted proteolysis and removing damaged proteins. Consequently, the UPS serves also as the first line of defense for cellular recovery following exposure to redox stressors. Paradoxically, the composition and function of the UPS can also be negatively targeted by redox unbalance through a vicious cycle. The alterations in redox balance and UPS biological mechanisms are involved in the etiopathogenesis of chronic eye disorders. These disorders encompass a diverse repertoire of pathologies affecting the retinal layers (e.g., age-related macular degeneration, diabetic retinopathy) and the optic nerve (e.g., glaucoma). Nowadays, the comprehension of the interplay between proteostasis and oxidative redox status remains pivotal for identifying new therapeutic approaches. Encouragingly, a number of anti-oxidant compounds have been reported to modulate proteasome activity against redox insults in vitro and in vivo. Furthermore, these compounds provide cytoprotective roles in both in vitro and animal models of eye diseases. Therefore, this review highlights recent research on the interplay of the UPS with oxidative stress in physio-pathological conditions, focusing on the onset and progression of ocular diseases, thereby providing new insights into UPS-oxidative stress interaction. Full article
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12 pages, 795 KB  
Article
Intraocular Cytokine Level Prediction from Fundus Images and Optical Coherence Tomography
by Hidenori Takahashi, Taiki Tsuge, Yusuke Kondo, Yasuo Yanagi, Satoru Inoda, Shohei Morikawa, Yuki Senoo, Toshikatsu Kaburaki, Tetsuro Oshika and Toshihiko Yamasaki
Sensors 2025, 25(23), 7382; https://doi.org/10.3390/s25237382 - 4 Dec 2025
Viewed by 508
Abstract
The relationship between retinal images and intraocular cytokine profiles remains largely unexplored, and no prior work has systematically compared fundus- and OCT-based deep learning models for cytokine prediction. We aimed to predict intraocular cytokine concentrations using color fundus photographs (CFP) and retinal optical [...] Read more.
The relationship between retinal images and intraocular cytokine profiles remains largely unexplored, and no prior work has systematically compared fundus- and OCT-based deep learning models for cytokine prediction. We aimed to predict intraocular cytokine concentrations using color fundus photographs (CFP) and retinal optical coherence tomography (OCT) with deep learning. Our pipeline consisted of image preprocessing, convolutional neural network–based feature extraction, and regression modeling for each cytokine. Deep learning was implemented using AutoGluon, which automatically explored multiple architectures and converged on ResNet18, reflecting the small dataset size. Four approaches were tested: (1) CFP alone, (2) CFP plus demographic/clinical features, (3) OCT alone, and (4) OCT plus these features. Prediction performance was defined as the mean coefficient of determination (R2) across 34 cytokines, and differences were evaluated using paired two-tailed t-tests. We used data from 139 patients (152 eyes) and 176 aqueous humor samples. The cohort consisted of 85 males (61%) with a mean age of 73 (SD 9.8). Diseases included 64 exudative age-related macular degeneration, 29 brolucizumab-associated endophthalmitis, 19 cataract surgeries, 15 retinal vein occlusion, and 8 diabetic macular edema. Prediction performance was generally poor, with mean R2 values below zero across all approaches. The CFP-only model (–0.19) outperformed CFP plus demographics (–24.1; p = 0.0373), and the OCT-only model (–0.18) outperformed OCT plus demographics (–14.7; p = 0.0080). No significant difference was observed between CFP and OCT (p = 0.9281). Notably, VEGF showed low predictability (31st with CFP, 12th with OCT). Full article
(This article belongs to the Section Optical Sensors)
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12 pages, 1073 KB  
Article
Clinical Characteristics of Patients with Neovascular Age-Related Macular Degeneration and Responses to Anti-VEGF Therapy: Four-Group Stratification Based on Drusen and Punctate Hyperfluorescence
by Hiroyuki Kamao, Katsutoshi Goto, Kenichi Mizukawa, Ryutaro Hiraki, Atsushi Miki and Shuhei Kimura
J. Clin. Med. 2025, 14(23), 8593; https://doi.org/10.3390/jcm14238593 - 4 Dec 2025
Viewed by 369
Abstract
Background/Objectives: Different disease subtypes in neovascular age-related macular degeneration (nAMD) influence treatment burden, yet existing classifications such as the pachychoroid neovasculopathy (PNV)/non-PNV dichotomy may not fully capture clinical heterogeneity. This study aimed to compare the 12-month outcomes of intravitreal aflibercept (IVA) in [...] Read more.
Background/Objectives: Different disease subtypes in neovascular age-related macular degeneration (nAMD) influence treatment burden, yet existing classifications such as the pachychoroid neovasculopathy (PNV)/non-PNV dichotomy may not fully capture clinical heterogeneity. This study aimed to compare the 12-month outcomes of intravitreal aflibercept (IVA) in treatment-naïve patients with unilateral nAMD stratified by the presence or absence of drusen and punctate hyperfluorescence (PH). Methods: This retrospective study included 130 eyes of 130 patients categorized into the Drusen−/PH−, Drusen+/PH−, Drusen−/PH+, and Drusen+/PH+ groups. Their best-corrected visual acuity, retinal thickness, choroidal thickness, number of injections, no-retinal fluid rate during the loading dose regimen, and 12-month retreatment rate following treatment initiation were determined. The primary outcome was 12-month retreatment rate for the four groups, which was determined using Kaplan–Meier curves and log-rank tests. Exploratory metric multidimensional scaling (MDS) was used to visualize the baseline profiles. Results: The 12-month retreatment rates of the groups were significantly different. The Drusen+/PH− group had a higher retreatment rate and required more injections than the Drusen−/PH+ and Drusen+/PH+ groups. The Drusen+/PH− group was older than the Drusen−/PH+ and Drusen−/PH− groups. The Drusen−/PH+ group had a thicker choroid than the Drusen+/PH− group. The MDS results clear separation of the groups, consistent with the older age of the Drusen+/PH− group and the thicker choroid of the Drusen−/PH+ group. Conclusions: nAMD stratified based on drusen and PH differed in age, choroidal thickness, and IVA outcomes. The four-category framework provides greater pathophysiologic and therapeutic resolution than the simple PNV/non-PNV dichotomy and may help anticipate injection demand to guide individualized dosing strategies. Full article
(This article belongs to the Special Issue An Update on Retinal Diseases: From Diagnosis to Treatment)
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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
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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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Review
Associations Between Nutritional Factors, Obesity and Ocular Diseases: A Narrative Literature Review
by Corina Georgiana Bogdănici, Camelia Margareta Bogdănici, Irina Andreea Pavel, Cosmin Victor Ganea, Vlad Constantin Donica and Elena Mihaela Cărăușu
Nutrients 2025, 17(23), 3798; https://doi.org/10.3390/nu17233798 - 3 Dec 2025
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Abstract
Background: Nutritional imbalances significantly affect ocular physiology, contributing to dry eye disease, cataracts, age-related macular degeneration (AMD), and optic neuropathies. This review summarizes recent evidence on how micronutrient deficiencies and obesity influence eye health. Methods: A narrative search was performed in [...] Read more.
Background: Nutritional imbalances significantly affect ocular physiology, contributing to dry eye disease, cataracts, age-related macular degeneration (AMD), and optic neuropathies. This review summarizes recent evidence on how micronutrient deficiencies and obesity influence eye health. Methods: A narrative search was performed in PubMed, Scopus, and ScienceDirect (last 10 years). Human studies evaluating associations between micronutrients, dietary patterns, obesity, and ocular diseases were included. Out of 843 records, 50 studies met the eligibility criteria. Results: Deficiencies in vitamins A, D, E, C, and B-complex were consistently linked to ocular surface inflammation, retinal oxidative stress, cataracts, AMD, and nutritional optic neuropathies. Altered levels of zinc, copper, selenium, and magnesium were associated with impaired photoreceptor function, glaucoma risk, and retinal degeneration. Obesity emerged as an independent risk factor for AMD, diabetic retinopathy, and glaucoma through mechanisms involving oxidative stress and vascular dysfunction. Evidence from AREDS/AREDS2 supports targeted antioxidant supplementation in intermediate AMD. Conclusions: Adequate nutritional status and metabolic balance play a critical role in preserving ocular health. Early detection and correction of deficiencies may prevent or slow the progression of several eye diseases. Further high-quality trials are needed to define optimal nutritional recommendations. Full article
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