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Keywords = peripheral retinal degeneration

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12 pages, 1413 KiB  
Article
Posterior Vitreous Detachment in Healthy Versus AMD Eyes Assessed by Widefield Optical Coherence Tomography
by Maciej Gawęcki, Krzysztof Kiciński, Andrzej Grzybowski and Sławomir Teper
Diagnostics 2025, 15(11), 1382; https://doi.org/10.3390/diagnostics15111382 - 29 May 2025
Viewed by 898
Abstract
Introduction: This study aimed to determine the frequency of posterior vitreous detachment (PVD) in dry and wet age-related macular degeneration (AMD) patients compared with healthy eyes via ultrawide field optical coherence tomography (UWF–OCT). Additionally, the retinal thicknesses in the central and peripheral zones [...] Read more.
Introduction: This study aimed to determine the frequency of posterior vitreous detachment (PVD) in dry and wet age-related macular degeneration (AMD) patients compared with healthy eyes via ultrawide field optical coherence tomography (UWF–OCT). Additionally, the retinal thicknesses in the central and peripheral zones of AMD patients and the control group were compared. Methods: We included 123 eyes from 83 participants with dry AMD, 123 from 87 participants with wet AMD, and 85 from 53 healthy controls. All three study groups were compared according to age, sex, best corrected visual acuity (BCVA), PVD stage, axial length, and retinal thickness in the central, perifoveal, and peripheral zones. Additional analyses included correlations between the BCVA and PVD stage and between retinal thickness and the PVD stage. Results: Complete separation of the vitreous from the macula was significantly more common in AMD patients than in the control group, as noted in 47 eyes (55.29%) in the control group, 92 eyes (74.80%) in the wet AMD group, and 93 eyes (75.61%) in the dry AMD group. The PVD stage did not significantly influence retinal thickness. BCVA in AMD patients did not correlate with the PVD stage. Conclusions: Complete PVD is more common in AMD patients than in healthy controls, as evaluated by UWF–OCT. No relationship between the PVD stage and AMD type or BCVA was observed. Full article
(This article belongs to the Special Issue Latest Advances in Ophthalmic Imaging)
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14 pages, 3124 KiB  
Article
Exploring the Risk: Peripheral Retinal Degenerations in Young Australian Adults
by Natalie Ann Watt, Nicholas Hockley and James Andrew Armitage
J. Clin. Med. 2025, 14(10), 3501; https://doi.org/10.3390/jcm14103501 - 16 May 2025
Viewed by 508
Abstract
Background/Objectives: Peripheral retinal degenerations (PRDs) are structural anomalies in the outer regions of the retina, typically emerging in adolescence and early adulthood. Early detection is crucial, as some PRDs can lead to sight-threatening complications, such as retinal detachment, if left unmanaged. Due to [...] Read more.
Background/Objectives: Peripheral retinal degenerations (PRDs) are structural anomalies in the outer regions of the retina, typically emerging in adolescence and early adulthood. Early detection is crucial, as some PRDs can lead to sight-threatening complications, such as retinal detachment, if left unmanaged. Due to a paucity of research regarding PRDs and their association with axial length (AL) and refractive error (RE) in young Australian adults, this study aimed to investigate the prevalence of PRDs in this population and establish whether AL and RE could help predict the likelihood of PRD occurrence. Methods: A cross-sectional study was conducted on a mixed population (n = 221) of Australian adults aged 18 to 40. Demographic data, RE, AL, and a series of ultra-widefield (UWF) retinal images were obtained from participants’ undilated eyes using the Zeiss ClarusTM 500. Results: The overall PRD prevalence was 8.15% (n = 442 eyes). Binary logistic regression revealed that a longer AL was a more significant factor in increasing the risk of PRD development across all myopia classifications compared to emmetropia than RE. The likelihood of a PRD was 50% at an AL of 26.9 mm and −6.50D of myopia, and 95% at 29.6 mm and −11.00D. Conclusions: PRD prevalence was lower than reported in other global studies, perhaps reflecting the diverse ethnic makeup of the cohort. While our study supports the conventional understanding that longer ALs, and high myopia are key risk factors for developing a PRD, it also provides new insights into the likelihood of detecting a PRD at a given AL or RE in a mixed population. This information is crucial for eye care practitioners, enabling early identification of at-risk individuals and screening for PRDs that may increase the risk of retinal detachment. Full article
(This article belongs to the Special Issue Advanced Research in Myopia and Other Visual Disorders)
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7 pages, 8880 KiB  
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A Rare Vitreoretinal Degenerative Disorder: Goldmann–Favre Syndrome Complicated with Choroidal Neovascularization in a Pediatric Patient
by Klaudia Szala and Bogumiła Wójcik-Niklewska
Diagnostics 2025, 15(5), 622; https://doi.org/10.3390/diagnostics15050622 - 5 Mar 2025
Viewed by 857
Abstract
Goldmann–Favre syndrome (GFS) is a rare vitreoretinal degenerative disorder caused by mutations in the NR2E3 gene located on the short arm of chromosome 15. This condition, inherited in an autosomal recessive manner, was first described by Favre in two siblings, with Ricci later [...] Read more.
Goldmann–Favre syndrome (GFS) is a rare vitreoretinal degenerative disorder caused by mutations in the NR2E3 gene located on the short arm of chromosome 15. This condition, inherited in an autosomal recessive manner, was first described by Favre in two siblings, with Ricci later confirming its hereditary pattern. In GFS, rod photoreceptors are essentially replaced by S-cone photoreceptors. Enhanced S-Cone Syndrome (ESCS) and Goldmann–Favre syndrome are two distinct entities within the spectrum of retinal degenerative diseases, both caused by mutations in the NR2E3 gene. Despite sharing a common genetic basis, these conditions exhibit significantly different clinical phenotypes. ESCS is characterized by an excessive number of S-cones (blue-sensitive cones) with degeneration of rods and L-/M-cones, leading to increased sensitivity to blue light and early-onset night blindness. In contrast, GFS is considered a more severe form of ESCS, involving additional features such as retinal schisis, vitreous degeneration, and more pronounced visual impairment. GFS typically manifests in the first decade of life as night blindness (nyctalopia) and progressive visual acuity impairment. The clinical features include degenerative vitreous changes such as liquefaction, strands, and bands, along with macular and peripheral retinoschisis, posterior subcapsular cataract, atypical pigmentary dystrophy, and markedly abnormal or nondetectable electroretinograms (ERGs). Although peripheral retinoschisis is more common in GFS, central retinoschisis may also occur. Despite the consistent genetic basis, the phenotype of GFS can vary significantly among individuals. The differential diagnosis should consider diseases within the retinal degenerative spectrum, including retinitis pigmentosa, congenital retinoschisis, and secondary pigmentary retinopathy. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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10 pages, 826 KiB  
Article
Central Serous Chorioretinopathy and Ocular Comorbidities
by Anindya Samanta, Matthew Driban, Niroj Sahoo, Deepika Parameswarappa, Sumit Randhir Singh, Sonny Caplash, Pranjal Mishra, Rohit Agrawal, Ramesh Venkatesh, Dmitrii S. Maltsev and Jay Chhablani
J. Clin. Med. 2025, 14(3), 720; https://doi.org/10.3390/jcm14030720 - 23 Jan 2025
Viewed by 1116
Abstract
Background/Objectives: Central serous chorioretinopathy (CSCR) is a common retinopathy that can present with other concurrent diseases; thus, further research into the prevalence of other ocular comorbidities in eyes with CSCR is required. Methods: This retrospective, multicentric, cross-sectional observational study [...] Read more.
Background/Objectives: Central serous chorioretinopathy (CSCR) is a common retinopathy that can present with other concurrent diseases; thus, further research into the prevalence of other ocular comorbidities in eyes with CSCR is required. Methods: This retrospective, multicentric, cross-sectional observational study reviewed the charts of 9157 patients. Of them, 579 (6.32%) patients and 766 eyes had an additional ocular comorbidity, in addition to CSCR, in at least one subject eye. Results: The baseline best-corrected visual acuity (BCVA) of the subjects eyes was 0.49 ± 0.36 logMAR. The average BCVA of subject eyes with coexisting macular diseases was 0.50 logMAR, while the corresponding BCVA of subject eyes with coexisting peripheral disease was 0.55 logMAR. The most prevalent coexisting macular diseases were non-proliferative diabetic retinopathy (26.8%), non-exudative age-related macular degeneration (AMD) (7.6%) and hypertensive retinopathy (3.0%). The most prevalent coexisting non-macular diseases were lattice degeneration (8.9%), optic atrophy (5.1%), rhegmatogenous retinal detachment (1.70%) and optic disc pit (1.7%). The odds of having a comorbid disease in the same eye as CSCR were statistically significant for branch retinal vein occlusion (OR 11.56, p-value = 0.02) and non-exudative AMD (OR 2.06; p-value = 0.01); additionally, there was a trend towards significance for idiopathic polypoidal choroidal vasculopathy (OR 4.43; p-value = 0.05) when compared to the eyes without CSCR. Conclusions: Certain diseases are more likely to coexist in eyes with CSCR. Additionally, eyes with CSCR may have statistically significant odds of certain diseases when compared to eyes without CSCR. Full article
(This article belongs to the Section Ophthalmology)
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12 pages, 2736 KiB  
Article
Ultra-Wide-Field OCT Measurements in Patients with Age-Related Macular Degeneration in Relation to Their Visual Function
by Maciej Gawęcki, Krzysztof Kiciński, Jan Kucharczuk, Sławomir Teper, Magdalena Hubert and Tomasz Kuc
Diagnostics 2024, 14(24), 2868; https://doi.org/10.3390/diagnostics14242868 - 20 Dec 2024
Viewed by 825
Abstract
Background: Ultra-wide-field optical coherence tomography (UWF-OCT) devices have recently been introduced to clinical practice. The goal of this study was to compare choroidal and retinal thickness (CT and RT) in age-related macular degeneration (AMD) with a healthy control group using UWF-OCT Xephilio S1. [...] Read more.
Background: Ultra-wide-field optical coherence tomography (UWF-OCT) devices have recently been introduced to clinical practice. The goal of this study was to compare choroidal and retinal thickness (CT and RT) in age-related macular degeneration (AMD) with a healthy control group using UWF-OCT Xephilio S1. Additionally, we sought to determine the relationship between the RT and CT of patients with AMD, measured in different sectors, and their visual acuity. Methods: The study included 104 eyes from 74 participants with dry AMD, 119 eyes from 86 participants with wet AMD, and 85 eyes from 53 healthy controls. Of the participants with wet AMD, 87 eyes received anti-VEGF treatment, 13 were treatment naïve, and 19 had incomplete data. The analyzed measurements were taken in the central area of 3 mm in diameter and two peripheral rings located between 3–9 mm and 9–18 mm diameters. Results. There was no significant variation in the RT in any sector between the three study groups. CT in dry and wet AMD cohorts was significantly lower compared to controls in every sector. Patients with treatment-naïve wet AMD did not demonstrate significant CT loss but had a tendency for lower CT values. Visual impairment in patients with AMD correlated with older age in both subgroups and with smaller RT in the dry AMD subgroup. Conclusions: Values of RT and CT obtained at the mid- and far-periphery with UWF-OCT generally reflect the alterations observed in AMD in the central part of the posterior pole. Intravitreal anti-VEGF treatment might contribute to loss of choroidal tissue observed in AMD in every sector. Full article
(This article belongs to the Special Issue Images in the Diagnosis and Treatment of Macular Edema)
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20 pages, 2971 KiB  
Article
Intravitreal Metformin Protects Against Choroidal Neovascularization and Light-Induced Retinal Degeneration
by Jason F. Xiao, Wendy Luo, Amir Mani, Hugo Barba, Aniruddhsingh Solanki, Steven Droho, Jeremy A. Lavine and Dimitra Skondra
Int. J. Mol. Sci. 2024, 25(21), 11357; https://doi.org/10.3390/ijms252111357 - 22 Oct 2024
Cited by 3 | Viewed by 4500
Abstract
Neovascular age-related macular degeneration (nAMD), a leading cause of blindness in older adults, presents a challenging pathophysiology involving choroidal neovascularization (CNV) and retinal degeneration. Current treatments relying on intravitreal (IVT) administration of anti-angiogenic agents are costly and of moderate effectiveness. Metformin, the common [...] Read more.
Neovascular age-related macular degeneration (nAMD), a leading cause of blindness in older adults, presents a challenging pathophysiology involving choroidal neovascularization (CNV) and retinal degeneration. Current treatments relying on intravitreal (IVT) administration of anti-angiogenic agents are costly and of moderate effectiveness. Metformin, the common anti-diabetic drug, has been associated with decreased odds of developing AMD. Studies have shown that metformin can mitigate cellular aging, neoangiogenesis, and inflammation across multiple diseases. This preclinical study assessed metformin’s impact on vessel growth using choroidal explants before exploring IVT metformin’s effects on laser-induced CNV and light-induced retinal degeneration in C57BL/6J and BALB/cJ mice, respectively. Metformin reduced new vessel growth in choroidal explants in a dose-dependent relationship. Following laser induction, IVT metformin suppressed CNV and decreased peripheral infiltration of IBA1+ macrophages/microglia. Furthermore, IVT metformin protected against retinal thinning in response to light-induced degeneration. IVT metformin downregulated genes in the choroid and retinal pigment epithelium which are associated with angiogenesis and inflammation, two key processes that drive nAMD progression. These findings underscore metformin’s capacity as an anti-angiogenic and neuroprotective agent, demonstrating this drug’s potential as an accessible option to help manage nAMD. Full article
(This article belongs to the Special Issue Age-Related Macular Degeneration and Diabetic Retinopathy)
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19 pages, 5473 KiB  
Article
Arylphthalide Delays Diabetic Retinopathy via Immunomodulating the Early Inflammatory Response in an Animal Model of Type 1 Diabetes Mellitus
by Francisco Martín-Loro, Fátima Cano-Cano, María J. Ortega, Belén Cuevas, Laura Gómez-Jaramillo, María del Carmen González-Montelongo, Jan Cedric Freisenhausen, Almudena Lara-Barea, Antonio Campos-Caro, Eva Zubía, Manuel Aguilar-Diosdado and Ana I. Arroba
Int. J. Mol. Sci. 2024, 25(15), 8440; https://doi.org/10.3390/ijms25158440 - 2 Aug 2024
Cited by 2 | Viewed by 1825
Abstract
Diabetic retinopathy (DR) is one of the most prevalent secondary complications associated with diabetes. Specifically, Type 1 Diabetes Mellitus (T1D) has an immune component that may determine the evolution of DR by compromising the immune response of the retina, which is mediated by [...] Read more.
Diabetic retinopathy (DR) is one of the most prevalent secondary complications associated with diabetes. Specifically, Type 1 Diabetes Mellitus (T1D) has an immune component that may determine the evolution of DR by compromising the immune response of the retina, which is mediated by microglia. In the early stages of DR, the permeabilization of the blood–retinal barrier allows immune cells from the peripheral system to interact with the retinal immune system. The use of new bioactive molecules, such as 3-(2,4-dihydroxyphenyl)phthalide (M9), with powerful anti-inflammatory activity, might represent an advance in the treatment of diseases like DR by targeting the immune systems responsible for its onset and progression. Our research aimed to investigate the molecular mechanisms involved in the interaction of specific cells of the innate immune system during the progression of DR and the reduction in inflammatory processes contributing to the pathology. In vitro studies were conducted exposing Bv.2 microglial and Raw264.7 macrophage cells to proinflammatory stimuli for 24 h, in the presence or absence of M9. Ex vivo and in vivo approaches were performed in BB rats, an animal model for T1D. Retinal explants from BB rats were cultured with M9. Retinas from BB rats treated for 15 days with M9 via intraperitoneal injection were analyzed to determine survival, cellular signaling, and inflammatory markers using qPCR, Western blot, or immunofluorescence approaches. Retinal structure images were acquired via Spectral-Domain–Optical Coherence Tomography (SD-OCT). Our results show that the treatment with M9 significantly reduces inflammatory processes in in vitro, ex vivo, and in vivo models of DR. M9 works by inhibiting the proinflammatory responses during DR progression mainly affecting immune cell responses. It also induces an anti-inflammatory response, primarily mediated by microglial cells, leading to the synthesis of Arginase-1 and Hemeoxygenase-1(HO-1). Ultimately, in vivo administration of M9 preserves the retinal integrity from the degeneration associated with DR progression. Our findings demonstrate a specific interaction between both retinal and systemic immune cells in the progression of DR, with a differential response to treatment, mainly driven by microglia in the anti-inflammatory action. In vivo treatment with M9 induces a switch in immune cell phenotypes and functions that contributes to delaying the DR progression, positioning microglial cells as a new and specific therapeutic target in DR. Full article
(This article belongs to the Special Issue Advances in the Pathophysiology and Treatment of Diabetic Retinopathy)
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16 pages, 7400 KiB  
Article
Optimization of an Ischemic Retinopathy Mouse Model and the Consequences of Hypoxia in a Time-Dependent Manner
by Inez Bosnyak, Nelli Farkas, Dorottya Molitor, Balazs Meresz, Evelin Patko, Tamas Atlasz, Alexandra Vaczy and Dora Reglodi
Int. J. Mol. Sci. 2024, 25(15), 8008; https://doi.org/10.3390/ijms25158008 - 23 Jul 2024
Cited by 2 | Viewed by 1530
Abstract
The retina is one of the highest metabolically active tissues with a high oxygen consumption, so insufficient blood supply leads to visual impairment. The incidence of related conditions is increasing; however, no effective treatment without side effects is available. Furthermore, the pathomechanism of [...] Read more.
The retina is one of the highest metabolically active tissues with a high oxygen consumption, so insufficient blood supply leads to visual impairment. The incidence of related conditions is increasing; however, no effective treatment without side effects is available. Furthermore, the pathomechanism of these diseases is not fully understood. Our aim was to develop an optimal ischemic retinopathy mouse model to investigate the retinal damage in a time-dependent manner. Retinal ischemia was induced by bilateral common carotid artery occlusion (BCCAO) for 10, 13, 15 or 20 min, or by right permanent unilateral common carotid artery occlusion (UCCAO). Optical coherence tomography was used to follow the changes in retinal thickness 3, 7, 14, 21 and 28 days after surgery. The number of ganglion cells was evaluated in the central and peripheral regions on whole-mount retina preparations. Expression of glial fibrillary acidic protein (GFAP) was analyzed with immunohistochemistry and Western blot. Retinal degeneration and ganglion cell loss was observed in multiple groups. Our results suggest that the 20 min BCCAO is a good model to investigate the consequences of ischemia and reperfusion in the retina in a time-dependent manner, while the UCCAO causes more severe damage in a short time, so it can be used for testing new drugs. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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15 pages, 20382 KiB  
Article
Retro Mode Imaging for Detection and Quantification of Sub-RPE Drusen and Subretinal Drusenoid Deposits in Age-Related Macular Degeneration
by Marlene Saßmannshausen, Leyla Sautbaeva, Leon Alexander von der Emde, Marc Vaisband, Kenneth R. Sloan, Jan Hasenauer, Frank G. Holz and Thomas Ach
J. Clin. Med. 2024, 13(14), 4131; https://doi.org/10.3390/jcm13144131 - 15 Jul 2024
Cited by 2 | Viewed by 1814
Abstract
Background: Drusen and drusenoid deposits are a hallmark of age-related macular degeneration (AMD). Nowadays, a multimodal retinal imaging approach enables the detection of these deposits. However, quantitative data on subretinal drusenoid deposits (SDDs) are still missing. Here, we compare the capability of en-face [...] Read more.
Background: Drusen and drusenoid deposits are a hallmark of age-related macular degeneration (AMD). Nowadays, a multimodal retinal imaging approach enables the detection of these deposits. However, quantitative data on subretinal drusenoid deposits (SDDs) are still missing. Here, we compare the capability of en-face drusen and SDD area detection in eyes with non-exudative AMD using conventional imaging modalities versus Retro mode imaging. We also quantitatively assess the topographic distribution of drusen and SDDs. Methods: In total, 120 eyes of 90 subjects (mean age ± standard deviation = 74.6 ± 8.6 years) were included. Coherent en-face drusen and SDD areas were measured via near-infrared reflectance, green (G-) and blue (B-) fundus autofluorescence (AF), and Retro mode imaging. Drusen phenotypes were classified by correlating en-face drusen areas using structural high-resolution spectral domain optical coherence tomography. The topographic distribution of drusen was analyzed according to a modified ETDRS (Early Treatment of Diabetic Retinopathy Study) grid. Intraclass correlation coefficient (ICC) analysis was applied to determine the inter-reader agreement in the SDD en-face area assessment. Results: The largest coherent en-face drusen area was found using Retro mode imaging with a mean area of 105.2 ± 45.9 mm2 (deviated left mode (DL)) and 105.4 ± 45.5 mm2 (deviated right mode (DR)). The smallest en-face drusen areas were determined by GAF (50.9 ± 42.6 mm2) and BAF imaging (49.1 ± 42.9 mm2) (p < 0.001). The inter-reader agreement for SDD en-face areas ranged from 0.93 (DR) to 0.70 (BAF). The topographic analysis revealed the highest number of SDDs in the superior peripheral retina, whereas sub-retinal pigment epithelium drusen were mostly found in the perifoveal retina. Retro mode imaging further enabled the detection of the earliest SDD stages. Conclusions: Retro mode imaging allows for a detailed detection of drusen phenotypes. While hundreds/thousands of SDDs can be present in one eye, the impact of SDD number or volume on AMD progression still needs to be evaluated. However, this new imaging modality can add important knowledge on drusen development and the pathophysiology of AMD. Full article
(This article belongs to the Section Ophthalmology)
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16 pages, 37623 KiB  
Review
Advantages of the Utilization of Wide-Field OCT and Wide-Field OCT Angiography in Clinical Practice
by Maciej Gawęcki and Krzysztof Kiciński
Diagnostics 2024, 14(3), 321; https://doi.org/10.3390/diagnostics14030321 - 1 Feb 2024
Cited by 5 | Viewed by 3004
Abstract
Wide-field (WF) retinal imaging is becoming a standard diagnostic tool for diseases involving the peripheral retina. Technological progress elicited the advent of wide-field optical coherence tomography (WF-OCT) and WF-OCT angiography (WF-OCTA) examinations. This review presents the results of studies that analyzed the implementation [...] Read more.
Wide-field (WF) retinal imaging is becoming a standard diagnostic tool for diseases involving the peripheral retina. Technological progress elicited the advent of wide-field optical coherence tomography (WF-OCT) and WF-OCT angiography (WF-OCTA) examinations. This review presents the results of studies that analyzed the implementation of these procedures in clinical practice and refers to them as traditional and ultra-wide-field fluorescein angiography (UWF-FA). A PUBMED search was performed using the terms WF-OCT OR WF-OCTA OR UWF-FA AND the specific clinical entity, and another search for diabetic retinopathy (DR), retinal vein occlusion (RVO), Coats disease, peripheral retinal telangiectasia, peripheral retinal degeneration, lattice degeneration, and posterior vitreous detachment. The analysis only included the studies in which the analyzed field of view for the OCT or OCTA exam was larger than 55 degrees. The evaluation of the extracted studies indicates that WF imaging with OCT and OCTA provides substantial information on retinal disorders involving the peripheral retina. Vascular diseases, such as DR or RVO, can be reliably evaluated using WF-OCTA with results superior to standard-field fluorescein angiography. Nevertheless, UWF-FA provides a larger field of view and still has advantages over WF-OCTA concerning the evaluation of areas of non-perfusion and peripheral neovascularization. Detailed information on the vascular morphology of peripheral changes should be obtained via WF-OCTA and not angiographic examinations. WF-OCT can serve as a valuable tool for the detection and evaluation of vitreoretinal traction, posterior vitreous detachment, and peripheral retinal degeneration, and guide therapeutic decisions on a patient’s eligibility for surgical procedures. Full article
(This article belongs to the Special Issue State of the Art in Retinal Optical Coherence Tomography Images)
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15 pages, 1855 KiB  
Article
Inherited Retinal Degeneration Caused by Dehydrodolichyl Diphosphate Synthase Mutation–Effect of an ALG6 Modifier Variant
by Elisha Monson, Artur V. Cideciyan, Alejandro J. Roman, Alexander Sumaroka, Malgorzata Swider, Vivian Wu, Iryna Viarbitskaya, Samuel G. Jacobson, Steven J. Fliesler and Steven J. Pittler
Int. J. Mol. Sci. 2024, 25(2), 1004; https://doi.org/10.3390/ijms25021004 - 13 Jan 2024
Cited by 4 | Viewed by 2429
Abstract
Modern advances in disease genetics have uncovered numerous modifier genes that play a role in the severity of disease expression. One such class of genetic conditions is known as inherited retinal degenerations (IRDs), a collection of retinal degenerative disorders caused by mutations in [...] Read more.
Modern advances in disease genetics have uncovered numerous modifier genes that play a role in the severity of disease expression. One such class of genetic conditions is known as inherited retinal degenerations (IRDs), a collection of retinal degenerative disorders caused by mutations in over 300 genes. A single missense mutation (K42E) in the gene encoding the enzyme dehydrodolichyl diphosphate synthase (DHDDS), which is required for protein N-glycosylation in all cells and tissues, causes DHDDS-IRD (retinitis pigmentosa type 59 (RP59; OMIM #613861)). Apart from a retinal phenotype, however, DHDDS-IRD is surprisingly non-syndromic (i.e., without any systemic manifestations). To explore disease pathology, we selected five glycosylation-related genes for analysis that are suggested to have disease modifier variants. These genes encode glycosyltransferases (ALG6, ALG8), an ER resident protein (DDOST), a high-mannose oligosaccharyl transferase (MPDU1), and a protein N-glycosylation regulatory protein (TNKS). DNA samples from 11 confirmed DHDDS (K42E)-IRD patients were sequenced at the site of each candidate genetic modifier. Quantitative measures of retinal structure and function were performed across five decades of life by evaluating foveal photoreceptor thickness, visual acuity, foveal sensitivity, macular and extramacular rod sensitivity, and kinetic visual field extent. The ALG6 variant, (F304S), was correlated with greater macular cone disease severity and less peripheral rod disease severity. Thus, modifier gene polymorphisms may account for a significant portion of phenotypic variation observed in human genetic disease. However, the consequences of the polymorphisms may be counterintuitively complex in terms of rod and cone populations affected in different regions of the retina. Full article
(This article belongs to the Special Issue Retinal Degeneration—from Genetics to Therapy: Second Edition)
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24 pages, 6316 KiB  
Review
Sialic Acid Mimetic Microglial Sialic Acid-Binding Immunoglobulin-like Lectin Agonism: Potential to Restore Retinal Homeostasis and Regain Visual Function in Age-Related Macular Degeneration
by Michael J. Tolentino, Andrew J. Tolentino, Elizabeth M. Tolentino, Anitha Krishnan and Mohamed A. Genead
Pharmaceuticals 2023, 16(12), 1735; https://doi.org/10.3390/ph16121735 - 16 Dec 2023
Cited by 6 | Viewed by 2920
Abstract
Age-related macular degeneration (AMD), a leading cause of visual loss and dysfunction worldwide, is a disease initiated by genetic polymorphisms that impair the negative regulation of complement. Proteomic investigation points to altered glycosylation and loss of Siglec-mediated glyco-immune checkpoint parainflammatory and inflammatory homeostasis [...] Read more.
Age-related macular degeneration (AMD), a leading cause of visual loss and dysfunction worldwide, is a disease initiated by genetic polymorphisms that impair the negative regulation of complement. Proteomic investigation points to altered glycosylation and loss of Siglec-mediated glyco-immune checkpoint parainflammatory and inflammatory homeostasis as the main determinant for the vision impairing complications of macular degeneration. The effect of altered glycosylation on microglial maintained retinal para-inflammatory homeostasis and eventual recruitment and polarization of peripheral blood monocyte-derived macrophages (PBMDMs) into the retina can explain the phenotypic variability seen in this clinically heterogenous disease. Restoring glyco-immune checkpoint control with a sialic acid mimetic agonist targeting microglial/macrophage Siglecs to regain retinal para-inflammatory and inflammatory homeostasis is a promising therapeutic that could halt the progression of and improve visual function in all stages of macular degeneration. Full article
(This article belongs to the Special Issue Microglia and Astrocytes as Drug Targets)
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9 pages, 4453 KiB  
Case Report
Case Series on Autosomal Recessive Non-Syndromic Retinitis Pigmentosa Caused by POMGNT1 Mutations with a Report of a New Variant
by Ami Patel, Ruifeng Cui, James Vernon Odom and Monique Leys
J. Clin. Med. 2023, 12(24), 7549; https://doi.org/10.3390/jcm12247549 - 7 Dec 2023
Cited by 3 | Viewed by 1549
Abstract
Recessive Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) mutations can cause early onset muscle–eye–brain disease but have also more recently been associated with non-syndromic Retinitis Pigmentosa. In this case series, we describe three sisters affected by non-syndromic autosomal recessive POMGNT1 retinopathy with a report of [...] Read more.
Recessive Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) mutations can cause early onset muscle–eye–brain disease but have also more recently been associated with non-syndromic Retinitis Pigmentosa. In this case series, we describe three sisters affected by non-syndromic autosomal recessive POMGNT1 retinopathy with a report of a new variant. The three patients received care at West Virginia University Eye Institute, including full ophthalmic examination with additional fundus imaging, optical coherence tomography (OCT), electroretinogram (ERG), and visual field testing. Diagnostic panel testing of 330 genes was also obtained. The proband was seen for cataract evaluation at age 42, and her fundus examination was suggestive of retinitis pigmentosa. Her oldest sister had been treated for acute anterior uveitis with retinal vasculitis. Another sister was diagnosed with multiple sclerosis (MS) and peripheral retinal degeneration. Posterior subcapsular cataracts were diagnosed between age 42 and 55 in all three sisters, each with constricted fields with preserved central vision. We identified one pathogenic POMGNT1 variant (c.751 + 1G > A) and one likely pathogenic variant (c.1010T > C p.Ile337Thr) in all three sisters. A thorough family history and examination of the siblings with genotyping might have led to an earlier diagnosis of retinal inherited disease and avoidance of immunomodulatory treatment in the oldest sibling. Full article
(This article belongs to the Section Ophthalmology)
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14 pages, 1274 KiB  
Article
Systemic Evidence for Mitochondrial Dysfunction in Age-Related Macular Degeneration as Revealed by mtDNA Copy Number Measurements in Peripheral Blood
by Adriana Koller, Claudia Lamina, Caroline Brandl, Martina E. Zimmermann, Klaus J. Stark, Hansi Weissensteiner, Reinhard Würzner, Iris M. Heid and Florian Kronenberg
Int. J. Mol. Sci. 2023, 24(22), 16406; https://doi.org/10.3390/ijms242216406 - 16 Nov 2023
Cited by 5 | Viewed by 2227
Abstract
Mitochondrial dysfunction is a common occurrence in the aging process and is observed in diseases such as age-related macular degeneration (AMD). Increased levels of reactive oxygen species lead to damaged mitochondrial DNA (mtDNA), resulting in dysfunctional mitochondria, and, consequently, mtDNA causes further harm [...] Read more.
Mitochondrial dysfunction is a common occurrence in the aging process and is observed in diseases such as age-related macular degeneration (AMD). Increased levels of reactive oxygen species lead to damaged mitochondrial DNA (mtDNA), resulting in dysfunctional mitochondria, and, consequently, mtDNA causes further harm in the retinal tissue. However, it is unclear whether the effects are locally restricted to the high-energy-demanding retinal pigment epithelium or are also systematically present. Therefore, we measured mtDNA copy number (mtDNA-CN) in peripheral blood using a qPCR approach with plasmid normalization in elderly participants with and without AMD from the AugUR study (n = 2262). We found significantly lower mtDNA-CN in the blood of participants with early (n = 453) and late (n = 170) AMD compared to AMD-free participants (n = 1630). In regression analyses, we found lower mtDNA-CN to be associated with late AMD when compared with AMD-free participants. Each reduction of mtDNA-CN by one standard deviation increased the risk for late AMD by 24%. This association was most pronounced in geographic atrophy (OR = 1.76, 95% CI 1.19–2.60, p = 0.004), which has limited treatment options. These findings provide new insights into the relationship between mtDNA-CN in blood and AMD, suggesting that it may serve as a more accessible biomarker than mtDNA-CN in the retina. Full article
(This article belongs to the Special Issue Age-Related Macular Degeneration and Diabetic Retinopathy)
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18 pages, 10170 KiB  
Article
Localization of Calretinin, Parvalbumin, and S100 Protein in Nothobranchius guentheri Retina: A Suitable Model for the Retina Aging
by Marialuisa Aragona, Marilena Briglia, Caterina Porcino, Kamel Mhalhel, Marzio Cometa, Patrizia Germana Germanà, Giuseppe Montalbano, Maria Levanti, Rosaria Laurà, Francesco Abbate, Antonino Germanà and Maria Cristina Guerrera
Life 2023, 13(10), 2050; https://doi.org/10.3390/life13102050 - 13 Oct 2023
Cited by 4 | Viewed by 1749
Abstract
Calcium-binding proteins (CaBPs) are members of a heterogeneous family of proteins able to buffer intracellular Ca2+ ion concentration. CaBPs are expressed in the central and peripheral nervous system, including a subpopulation of retinal neurons. Since neurons expressing different CaBPs show different susceptibility [...] Read more.
Calcium-binding proteins (CaBPs) are members of a heterogeneous family of proteins able to buffer intracellular Ca2+ ion concentration. CaBPs are expressed in the central and peripheral nervous system, including a subpopulation of retinal neurons. Since neurons expressing different CaBPs show different susceptibility to degeneration, it could be hypothesized that they are not just markers of different neuronal subpopulations, but that they might be crucial in survival. CaBPs’ ability to buffer Ca2+ cytoplasmatic concentration makes them able to defend against a toxic increase in intracellular calcium that can lead to neurodegenerative processes, including those related to aging. An emergent model for aging studies is the annual killifish belonging to the Nothobranchius genus, thanks to its short lifespan. Members of this genus, such as Nothobranchius guentheri, show a retinal stratigraphy similar to that of other actinopterygian fishes and humans. However, according to our knowledge, CaBPs’ occurrence and distribution in the retina of N. guentheri have never been investigated before. Therefore, the present study aimed to localize Calretinin N-18, Parvalbumin, and S100 protein (S100p) in the N. guentheri retina with immunohistochemistry methods. The results of the present investigation demonstrate for the first time the occurrence of Calretinin N-18, Parvalbumin, and S100p in N. guentheri retina and, consequently, the potential key role of these CaBPs in the biology of the retinal cells. Hence, the suitability of N. guentheri as a model to study the changes in CaBPs’ expression patterns during neurodegenerative processes affecting the retina related both to disease and aging can be assumed. Full article
(This article belongs to the Section Physiology and Pathology)
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