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Keywords = ganglion cell layer (GCL)

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12 pages, 363 KiB  
Article
Changes in Retinal Nerve Fiber and Ganglion Cell Layers After Chemical Injury: A Prospective Study
by Justina Skruodyte, Justina Olechnovic and Pranas Serpytis
J. Clin. Med. 2025, 14(15), 5601; https://doi.org/10.3390/jcm14155601 (registering DOI) - 7 Aug 2025
Abstract
Background: Chemical eye burns are a serious ophthalmic emergency that can lead to permanent vision loss in severe cases. This study aims to evaluate structural changes in the posterior segment of the eye in individuals who have experienced chemical burns. Methods: The study [...] Read more.
Background: Chemical eye burns are a serious ophthalmic emergency that can lead to permanent vision loss in severe cases. This study aims to evaluate structural changes in the posterior segment of the eye in individuals who have experienced chemical burns. Methods: The study included 64 eyes from 54 patients with chemical burns (chemical burn group) and 87 healthy eyes from 87 subjects (control group), matched by age and sex. Patients had confirmed burns with limbal ischemia, no glaucoma, normal intraocular pressure, and no major ocular or systemic diseases. Burned eyes were examined during the acute phase and again at 3 months, with some followed up at 6 months if significant retinal asymmetry was detected. Retinal nerve fiber layer (RNFL) thickness was assessed in four quadrants, and ganglion cell complex (GCL++) thickness was analyzed using automated segmentation of optical coherence tomography (OCT) maps. Results: This study compared measurements between the burn group, the control group, and timepoints. OCT analysis revealed no significant difference in total RNFL thickness between burn patients and controls (mean difference: −1.14 µm, 95% CI: −3.92 to 1.64). Similarly, GCL++ thickness did not differ significantly between groups (mean difference: −0.97 µm, 95% CI: −3.31 to 1.37). At 6-month follow-up, a non-significant decline in both RNFL and GCL++ thicknesses was observed. Logistic regression identified higher Dua grade as an independent predictor of RNFL thinning (OR: 4.816, 95% CI: 1.103–21.030; p = 0.037). Patients with severe ocular chemical burns (Dua grade ≥ 3) demonstrated reduced RNFL thickness in all quadrants compared to healthy controls. The most pronounced reductions were observed in the nasal and superior quadrants (p = 0.007 and p = 0.069, respectively); however, after applying Bonferroni correction for multiple comparisons, only the difference in the nasal quadrant remained statistically significant (adjusted p = 0.035). Conclusions: Although overall RNFL and GCL++ thicknesses did not differ significantly between burn patients and healthy controls, patients with severe ocular chemical burns (Dua grade ≥ 3) showed a significant reduction in RNFL thickness, in the nasal quadrant. Higher Dua grade was identified as an independent predictor of RNFL thinning. These findings suggest a potential association between burn severity and posterior segment changes, highlighting the need for further longitudinal studies with larger cohorts. Full article
(This article belongs to the Section Ophthalmology)
14 pages, 785 KiB  
Article
Novel Structure–Function Models for Estimating Retinal Ganglion Cell Count Using Pattern Electroretinography in Glaucoma Suspects
by Andrew Tirsi, Isabella Tello, Timothy Foster, Rushil Kumbhani, Nicholas Leung, Samuel Potash, Derek Orshan and Celso Tello
Diagnostics 2025, 15(14), 1756; https://doi.org/10.3390/diagnostics15141756 - 11 Jul 2025
Viewed by 348
Abstract
Background/Objectives: The early detection of retinal ganglion cell (RGC) dysfunction is critical for timely intervention in glaucoma suspects (GSs). The combined structure–function index (CSFI), which uses visual field and optical coherence tomography (OCT) data to estimate RGC counts, may be of limited [...] Read more.
Background/Objectives: The early detection of retinal ganglion cell (RGC) dysfunction is critical for timely intervention in glaucoma suspects (GSs). The combined structure–function index (CSFI), which uses visual field and optical coherence tomography (OCT) data to estimate RGC counts, may be of limited utility in GSs. This study evaluates whether steady-state pattern electroretinogram (ssPERG)-derived estimates better predict early structural changes in GSs. Methods: Fifty eyes from 25 glaucoma suspects underwent ssPERG and spectral-domain OCT. Estimated RGC counts (eRGCC) were calculated using three parameters: ssPERG-Magnitude (eRGCCMag), ssPERG-MagnitudeD (eRGCCMagD), and CSFI (eRGCCCSFI). Linear regression and multivariable models were used to assess each model’s ability to predict the average retinal nerve fiber layer thickness (AvRNFLT), average ganglion cell layer–inner plexiform layer thickness (AvGCL-IPLT), and rim area. Results: eRGCCMag and eRGCCMagD were significantly correlated with eRGCCCSFI. Both PERG-derived models outperformed eRGCCCSFI in predicting AvRNFLT and AvGCL-IPLT, with eRGCCMagD showing the strongest association with AvGCL-IPLT. Conversely, the rim area was best predicted by eRGCCMag and eRGCCCSFI. These findings support a linear relationship between ssPERG parameters and early RGC structural changes, while the logarithmic nature of visual field loss may limit eRGCCCSFI’s predictive accuracy in GSs. Conclusions: ssPERG-derived estimates, particularly eRGCCMagD, better predict early structural changes in GSs than eRGCCCSFI. eRGCCMagD’s superior performance in predicting GCL-IPLT highlights its potential utility as an early biomarker of glaucomatous damage. ssPERG-based models offer a simpler and more sensitive tool for early glaucoma risk stratification, and may provide a clinical benchmark for tracking recoverable RGC dysfunction and treatment response. Full article
(This article belongs to the Special Issue Imaging and AI Applications in Glaucoma)
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20 pages, 1534 KiB  
Article
Retinal Vessel Diameter Reductions Are Associated with Retinal Ganglion Cell Dysfunction, Thinning of the Ganglion Cell and Inner Plexiform Layers, and Decreased Visual Field Global Indices in Glaucoma Suspects
by Andrew Tirsi, Nicholas Leung, Rohun Gupta, Sungmin Hong, Derek Orshan, Joby Tsai, Corey Ross Lacher, Isabella Tello, Samuel Potash, Timothy Foster, Rushil Kumbhani and Celso Tello
Diagnostics 2025, 15(13), 1700; https://doi.org/10.3390/diagnostics15131700 - 3 Jul 2025
Viewed by 450
Abstract
Background/Objectives: The aim of this study was to evaluate the associations between optical coherence tomography angiography (OCTA)-based retinal vessel diameter (RVD) measurements, with retinal ganglion cell (RGC) function assessed by means of steady-state pattern electroretinography (ssPERG) using ganglion cell layer-inner plexiform layer [...] Read more.
Background/Objectives: The aim of this study was to evaluate the associations between optical coherence tomography angiography (OCTA)-based retinal vessel diameter (RVD) measurements, with retinal ganglion cell (RGC) function assessed by means of steady-state pattern electroretinography (ssPERG) using ganglion cell layer-inner plexiform layer thickness (GCL-IPLT) measurements and with Humphrey field analyzer (HFA) global indices in glaucoma suspects (GSs). Methods: Thirty-one eyes (20 participants) underwent a comprehensive ophthalmologic examination, ssPERG measurements utilizing the PERGLA paradigm, HFA, optical coherence tomography (OCT), and OCTA. The OCTA scans were processed using ImageJ software, Version 1.53, allowing for measurement of the RVD. Multiple linear regression models were used. Results: After controlling for age, race, central corneal thickness (CCT), and spherical equivalent (SE), a linear regression analysis found that the RVD explained the 4.7% variance in magnitude (Mag) (p = 0.169), 9.2% variance in magnitudeD (MagD) (p = 0.021), and 16.9% variance in magnitudeD/magnitude (p = 0.009). After controlling for age, CCT, and signal strength (SS), a linear regression analysis found that the RVD was significantly associated with the GCL-IPLT measurements (average GCL-IPL, minimum GCL-IPL, superior, superonasal, inferior, and inferonasal sectors) (p ≤ 0.023). An identical regression analysis where the RVD was replaced with the PERG parameters showed a significant association between the MagD and almost all GCI-IPLT measurements. RVD measurements were significantly associated with HFA VFI 24-2 (p = 0.004), MD 24-2 (p < 0.001), and PSD 24-2 (p = 0.009). Conclusions: Decreased RVD measurements were significantly associated with RGC dysfunction, decreased GCL-IPLT, and all HFA global indices in the GSs. Full article
(This article belongs to the Special Issue Imaging and AI Applications in Glaucoma)
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17 pages, 3664 KiB  
Article
Neuroprotective Effect of Methylene Blue in a Rat Model of Traumatic Optic Neuropathy
by Nicolás S. Ciranna, Ronan Nakamura, Rafael Peláez, Álvaro Pérez-Sala, Patricia Sarrión, Juan C. Fernández, Alejandra Paganelli, Agustín P. Aranalde, Ulises P. Ruiz, Juan J. López-Costa, César F. Loidl, Alfredo Martínez and Manuel Rey-Funes
Pharmaceuticals 2025, 18(6), 920; https://doi.org/10.3390/ph18060920 - 19 Jun 2025
Viewed by 784
Abstract
Background: Traumatic optic neuropathy (TON) represents a major cause of vision loss worldwide, and treatment options are limited. Here, we study whether methylene blue (MB), a free radical scavenger, is able to prevent morphological and electrophysiological hallmarks of neuropathy in an animal [...] Read more.
Background: Traumatic optic neuropathy (TON) represents a major cause of vision loss worldwide, and treatment options are limited. Here, we study whether methylene blue (MB), a free radical scavenger, is able to prevent morphological and electrophysiological hallmarks of neuropathy in an animal model of TON. Methods: The left eyes of Wistar rats were subjected to intraorbital nerve crush (IONC) while the right ones were sham operated. The group of rats treated with MB (n = 16) received five intraperitoneal injections with 2.0 mg/kg MB in the 24 h following IONC while the control group (n = 16) received just vehicle (PBS) as a control. Twenty-one days after surgery, scotopic full field (scERG), scotopic oscillatory potentials (OP), photopic full field (phERG) and pattern (PERG) electroretinography were performed for retinal function assessment. Furthermore, the number of cell nuclei in the ganglion cell layer (GCL) was recorded in post mortem histological sections. Results: IONC induced very significant reductions in electrophysiological parameters including scotopic a- and b-wave, OPs, photopic b-wave, PhNR amplitude and N2 amplitude. In addition, it also generated a significant prolongation of the N2 implicit time, indicating a profound impact on retinal function. This was further corroborated by a very significant reduction in the number of neuronal nuclei in the GCL, suggesting an intense loss and functional impairment of retinal ganglion cells. MB treatment was able to prevent, partially or completely, all those parameters, indicating the efficiency of such approach. Conclusions: Since MB is already approved for clinical use and presents a high safety profile, it could be repurposed as a neuroprotective drug for ophthalmological applications once proper phase 2 clinical trials are accomplished. Full article
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17 pages, 2351 KiB  
Article
The Value of Optical Coherence Tomography in Patients with Pituitary Adenoma and Its Association with Clinical Features: A Pilot Study
by Monika Duseikaite, Alvita Vilkeviciute, Igne Dumbliauskaite, Brigita Glebauskiene, Indre Zostautiene, Vita Rovite, Sheng-Nan Wu, Arimantas Tamasauskas and Rasa Liutkeviciene
J. Clin. Med. 2025, 14(12), 4318; https://doi.org/10.3390/jcm14124318 - 17 Jun 2025
Viewed by 1035
Abstract
Background: The main mechanism of optic nerve damage in patients with pituitary adenoma (PA) is the pressure of optic chiasm. The retinal nerve fiber layer (RNFL), the ganglion cell layer (GCL)+, and GCL++ thickness measurement by optical coherence tomography (OCT), visual function [...] Read more.
Background: The main mechanism of optic nerve damage in patients with pituitary adenoma (PA) is the pressure of optic chiasm. The retinal nerve fiber layer (RNFL), the ganglion cell layer (GCL)+, and GCL++ thickness measurement by optical coherence tomography (OCT), visual function evaluation, and magnetic resonance imaging (MRI) can be used to predict visual function recovery. In our study, we investigated the associations between visual acuity (VA), visual field (VF), RNFL, GCL changes, and the findings of MRI in patients with PA. Methods: This study was conducted in the Departments of Ophthalmology and Neurosurgery of the Lithuanian University of Health Sciences Hospital. A total of 25 patients diagnosed with PA were included in the study group, and 27 healthy subjects were included in the control group. The thickness of the RNFL and ganglion cell layer (GCL+, GCL++) and optic nerve disc diameter was analysed with OCT. Moreover, an MRI was performed for patients with PA. Results: The RNFL thickness around the optic disk measured preoperatively was reduced significantly in the temporal quadrant in PA patients compared with the control group (median (min; max); mean rank: 73.5 (52; 109); 58.39 vs. 69.5 (16; 168); 46.14; p = 0.038). We found that it was reduced significantly only in the inferior quadrant of the macro-PA group compared to the micro-PA group (median (min; max); mean rank: 99.5 (61; 115); 21.07 vs. 106.5 (90; 121); 32.15), p = 0.008, respectively). The RNFL thickness was reduced significantly only in the inferior quadrant of the non-active PA group compared to the active PA group (median (min; max); mean rank: 118.5 (49; 144); 17.42 vs. 130.5 (77; 156); 28.05), p = 0.028, respectively). RNFL thickness was reduced significantly only in the temporal quadrant in the PA with suprasellar extension group compared to the PA without suprasellar extension group (median (min; max); mean rank: 67.5 (16; 99); 21.66 vs. 72 (58; 168); 30.39), p = 0.036, respectively). Furthermore, GCL++ thickness was reduced significantly in total and in superior and inferior sectors of the PA with suprasellar extension group compared to the PA without suprasellar extension group (median (min; max); mean rank: 98.5 (57; 113); 21.8; 101 (61; 121); 21.48 and 102.5 (59; 116); 21.71 vs. 103.5 (95; 115); 30.2; 106.5 (90; 115); 30.61 and 104.5 (95; 113); 30.32), p = 0.043; p = 0.028 and p = 0.038, respectively). In the control group, significant positive correlations were found between optic disc area and the total RNFL thickness (r = 0.440, p < 0.001). In the PA group, significant correlations were observed between optic rim area and total RNFL thickness (r = 0.493, p < 0.001) and all quadrants, with the strongest in the nasal quadrant (r = 0.503, p < 0.001). A moderate to strong negative correlation was found between visual field (VF) defects and RNFL thickness, with the strongest correlation observed in the superior quadrant. Conclusions: OCT offers a detailed insight into the microscopic structural and functional changes throughout the entire visual pathway in patients with PA. Our findings demonstrate a significant negative correlation between RNFL thickness and visual field defects, highlighting the clinical relevance of OCT measurements in visual function assessment. Moreover, the results suggest that optic rim area may be a more reliable indicator of RNFL thickness variations than optic disc area in patients with PA. Full article
(This article belongs to the Section Clinical Neurology)
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14 pages, 822 KiB  
Article
Optical Coherence Tomography (OCT) Findings in Post-COVID-19 Healthcare Workers
by Sanela Sanja Burgić, Mirko Resan, Milka Mavija, Saša Smoljanović Skočić, Sanja Grgić, Daliborka Tadić and Bojan Pajic
J. Imaging 2025, 11(6), 195; https://doi.org/10.3390/jimaging11060195 - 12 Jun 2025
Viewed by 1022
Abstract
Recent evidence suggests that SARS-CoV-2 may induce subtle anatomical changes in the retina, detectable through advanced imaging techniques. This retrospective case–control study utilized optical coherence tomography (OCT) to assess medium-term retinal alterations in 55 healthcare workers, including 25 individuals with PCR-confirmed COVID-19 and [...] Read more.
Recent evidence suggests that SARS-CoV-2 may induce subtle anatomical changes in the retina, detectable through advanced imaging techniques. This retrospective case–control study utilized optical coherence tomography (OCT) to assess medium-term retinal alterations in 55 healthcare workers, including 25 individuals with PCR-confirmed COVID-19 and 30 non-COVID-19 controls, all of whom had worked in COVID-19 clinical settings. Comprehensive ophthalmological examinations, including OCT imaging, were conducted six months after infection. The analysis considered demographic variables, comorbidities, COVID-19 severity, risk factors, and treatments received. Central macular thickness (CMT) was significantly increased in the post-COVID-19 group (p < 0.05), with a weak but statistically significant positive correlation between CMT and disease severity (r = 0.245, p < 0.05), suggesting potential post-inflammatory retinal responses. No significant differences were observed in retinal nerve fiber layer (RNFL) or ganglion cell complex (GCL + IPL) thickness. However, mild negative trends in inferior RNFL and average GCL+IPL thickness may indicate early neurodegenerative changes. Notably, patients with comorbidities exhibited a significant reduction in superior and inferior RNFL thickness, pointing to possible long-term neurovascular impairment. These findings underscore the value of OCT imaging in identifying subclinical retinal alterations following COVID-19 and highlight the need for continued surveillance in recovered patients, particularly those with pre-existing systemic conditions. Full article
(This article belongs to the Special Issue Learning and Optimization for Medical Imaging)
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18 pages, 5301 KiB  
Article
The Profile of Retinal Ganglion Cell Death and Cellular Senescence in Mice with Aging
by Wen-Ying Wang, Xin Bin, Yanxuan Xu, Si Chen, Shuyi Zhou, Shaowan Chen, Yingjie Cao, Kunliang Qiu and Tsz Kin Ng
Int. J. Mol. Sci. 2025, 26(12), 5436; https://doi.org/10.3390/ijms26125436 - 6 Jun 2025
Viewed by 2854
Abstract
Older age is a risk factor for glaucoma, in which progressive retinal ganglion cell (RGC) loss leads to visual field defects and irreversible visual impairment and even blindness. We recently identified the involvement of cellular senescence in RGC cell death post-optic nerve injury. [...] Read more.
Older age is a risk factor for glaucoma, in which progressive retinal ganglion cell (RGC) loss leads to visual field defects and irreversible visual impairment and even blindness. We recently identified the involvement of cellular senescence in RGC cell death post-optic nerve injury. Here we further aimed to delineate the profile of RGC survival in mice with aging, a physiological process with increasing cellular senescence. The numbers of senescent cells in the ganglion cell layer (GCL) significantly and progressively increased starting at 8 months of age. Yet, significant reduction of ganglion cell complex layer thickness began in the 10-month-old mice, and significant reduction in the number of RGCs began in the 12-month-old mice as compared to the 2-month-old mice. Meanwhile, pyroptosis and ferroptosis markers as well as cellular senescence-related cell cycle arrest proteins p15Ink4b, p16Ink4a, p21Cip1, and p53 were significantly and progressively increased in GCL. In contrast, there were no significant changes in dendritic field, complexity, and branches with increasing ages. Comparing between the 2- and 16-month-old mouse retinas, the differentially expressed genes were involved in the pathways of neurodegeneration, innate immunity, and mitochondrial ATP synthesis. In summary, this study revealed the gradual increase in senescent cells as well as pyroptosis and ferroptosis with progressive RGC reduction in mice with aging. Cellular senescence and the related cell death pathways are potential targets for age-related RGC reduction. Full article
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16 pages, 4152 KiB  
Article
Tauroursodeoxycholic Acid Protects Retinal Ganglion Cells and Reduces Inflammation in Mice Following Optic Nerve Crush
by Nan Zhang, Ying Li, Xian Zhang, Micah A. Chrenek, Jiaxing Wang, Preston E. Girardot, Jana T. Sellers, Eldon E. Geisert, John M. Nickerson and Jeffrey H. Boatright
Pharmaceuticals 2025, 18(4), 569; https://doi.org/10.3390/ph18040569 - 14 Apr 2025
Viewed by 873
Abstract
Purpose: The aim of this study was to investigate the protective effects of systemically administered tauroursodeoxycholic acid (TUDCA) in an optic nerve crush (ONC) mouse model of retinal ganglion cell (RGC) death. Methods: C57BL/6J mice were injected intraperitoneally (i.p.) three times per week [...] Read more.
Purpose: The aim of this study was to investigate the protective effects of systemically administered tauroursodeoxycholic acid (TUDCA) in an optic nerve crush (ONC) mouse model of retinal ganglion cell (RGC) death. Methods: C57BL/6J mice were injected intraperitoneally (i.p.) three times per week with TUDCA (500 mg/kg) for two weeks, after which unilateral ONC was performed. A control cohort was identically treated with a drug vehicle (phosphate buffered saline; PBS). A separate cohort did not undergo any injections or surgeries (this was termed the “Naïve” group). Pattern electroretinography (PERG) was recorded 3 days after ONC. Retinas were harvested for whole-mount immunofluorescence staining with an antibody against RGC marker Brn3a and imaged by fluorescent confocal microscopy. Apoptotic cells in the ganglion cell layer (GCL) were detected by Terminal Deoxynucleotidyl Transferase-Mediated dUTP Nick End Labeling (TUNEL) performed on fixed retina sections. Glial fibrillary acidic protein (GFAP) immunostaining on fixed retina sections was conducted to detect the activation of Müller cells. Total RNA was extracted from retinas and expression of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-10 was determined by digital droplet PCR (ddPCR). Results: TUDCA treatment preserved visual function as assessed by PERG. P1 and N2 amplitudes from the PBS-treated ONC group were significantly diminished compared to those of the Naïve group (p < 0.001). TUDCA treatment prevented this diminution. The amplitudes of P1 and N2 in the TUDCA-treated ONC group were statistically indistinguishable from those of the Naïve group and were higher than the PBS-treated ONC group (TUDCA+ONC vs. PBS+ONC, P1: 6.99 ± 0.89 µV vs. 3.60 ± 0.69 µV, p < 0.01; N2: −9.30 (IQR: −13.43–−6.44) µV vs. −4.47 (IQR: −10.26–−2.17) µV). TUDCA treatment preserved RGCs. The ONC-vehicle-only group had 25% fewer RGCs (Brn3a-positive cells) than Naïve eyes (p < 0.0001). TUDCA treatment nearly completely prevented this loss, preserving all but 7.7% of the RGCs, and the number of RGCs in the TUDCA-treated ONC group was significantly higher than in the PBS-treated ONC group (TUDCA+ONC vs. PBS+ONC, 1738.00 ± 14.43 cells per field vs. 1454.00 ± 6.55 cells per field, p < 0.0001). The number of TUNEL-positive cells in the GCL (Naïve vs. PBS+ONC group: 1.00 (IQR: 0.00–2.00) % vs. 37.00 (IQR: 8.50–48.50) %, p < 0.05) and GFAP-positive fibers transversing retina sections (Naïve vs. PBS+ONC group: 33.00 ± 1.15 vs. 185.70 ± 42.37 fibers/retina, p < 0.05), and the expression of IL-6, TNF-α were significantly greater in the PBS-treated ONC group compared to that of the Naïve group (Naïve vs. PBS+ONC group, IL-6: 0.07 (IQR: 0.06–0.31) vs. 0.99 (IQR: 0.56–1.47), p < 0.05, TNF-α: 0.19 ± 0.069 vs. 1.39 ± 0.23; p < 0.01), an increase not observed with TUDCA treatment. Conclusions: Systemic TUDCA treatment significantly preserved RGC function and survival in the mouse ONC model of RGC damage. TUDCA treatment prevented RGC apoptosis, Müller glial cell activation, and retinal expression of several inflammatory cytokines. These data suggest that TUDCA is a promising therapeutic candidate for preserving RGC numbers and function. Full article
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14 pages, 3960 KiB  
Article
Early Macular Ganglion Cell Loss in Leber Hereditary Optic Neuropathy, an Optical Coherence Tomography Biomarker to Differentiate Optic Neuritis
by Julian A. Zimmermann, Martin Dominik Leclaire, Jens Julian Storp, Tobias J. Brix, Nicole Eter, Julia Krämer and Julia Biermann
J. Clin. Med. 2025, 14(6), 1998; https://doi.org/10.3390/jcm14061998 - 15 Mar 2025
Viewed by 777
Abstract
Background/Objectives: Leber hereditary optic neuropathy (LHON) is often misdiagnosed in its early stages as idiopathic single isolated optic neuritis (SION) or multiple-sclerosis-associated optic neuritis (MS-ON) due to the young age of the patients, the subacute vision loss, and the central visual field [...] Read more.
Background/Objectives: Leber hereditary optic neuropathy (LHON) is often misdiagnosed in its early stages as idiopathic single isolated optic neuritis (SION) or multiple-sclerosis-associated optic neuritis (MS-ON) due to the young age of the patients, the subacute vision loss, and the central visual field defect. The aim of this retrospective study was to evaluate changes in the peripapillary RNFL and GCLT over time in patients with early LHON, MS-ON, and SION in order to differentiate Leber hereditary optic neuropathy (LHON) from optic neuritis (ON) in the early stages of the disease. Methods: Patients with LHON and ON (either idiopathic single isolated optic neuritis (SION) or ON as the first symptom of relapsing–remitting multiple sclerosis (MS-ON) were included. Optical coherence tomography (OCT) scans were reviewed. The inclusion criteria were at least one follow-up OCT examination and a definite diagnosis after examination. Changes in the peripapillary retinal nerve fibre layer (RNFL) and macular ganglion cell layer thickness (GCLT) in both groups were evaluated over time and compared with normative data. The analysis focused on the early phase (0–45 days) after symptom onset. Results: Nine LHON patients with early OCT scans and twenty patients with ON were included. Quantitative OCT analysis showed greater RNFL swelling in LHON compared to ON during the first 60 days after symptom onset. Between day 61 and day 120, subnormal RNFL values were observed in both groups compared to controls. Thereafter, the RNFL decreased continuously and severely in the LHON group. The RNFL of ON patients did not show a clear progression after day 120. The GCLT in five LHON eyes showed a strong and solid decrease from day 0 to day 45, which was stronger than the moderate atrophy measured in ON eyes. Continuous GCL atrophy was measured until day 121 in LHON, after which a floor effect was reached. The GCLT in the inner nasal and inner inferior sectors was significantly smaller in LHON compared to ON patients on days 0–45. Conclusions: Thinning of the GCLT occurs at an early stage in LHON patients. Thus, GCLT may become a diagnostic tool to differentiate LHON from ON in the early phase of disease. Full article
(This article belongs to the Section Ophthalmology)
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13 pages, 3592 KiB  
Article
The Beneficial Role of the Thyroid Hormone Receptor Beta 2 (thrb2) in Facilitating the First Feeding and Subsequent Growth in Medaka as Fish Larval Model
by Jiaqi Wu, Ke Lu, Ruipeng Xie, Chenyuan Zhu, Qiyao Luo and Xu-Fang Liang
Cells 2025, 14(5), 386; https://doi.org/10.3390/cells14050386 - 6 Mar 2025
Viewed by 892
Abstract
During the early growth stages of fish larvae, there are significant challenges to their viability, so improving their visual environment is essential to promoting their growth and survival. Following the successful knockout of thyroid hormone receptor beta 2 (thrb2) using Clustered [...] Read more.
During the early growth stages of fish larvae, there are significant challenges to their viability, so improving their visual environment is essential to promoting their growth and survival. Following the successful knockout of thyroid hormone receptor beta 2 (thrb2) using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 technology, there was an increase in the expression of UV opsin (short-wave-sensitive 1, sws1), while the expression of other cone opsins was significantly decreased. Further analysis of the retinal structure demonstrated that the thrb2 knockout resulted in an increased lens thickness and a decreased thickness of the ganglion cell layer (GCL), outer plexiform layer (OPL), and outer nuclear layer (ONL) in the retina. The slowing down of swimming speed under light conditions in thrb2−/− may be related to the decreased expression of phototransduction-related genes such as G protein-coupled receptor kinase 7a (grk7a), G protein-coupled receptor kinase 7b (grk7b), and phosphodiesterase 6c (pde6c). Notably, thrb2−/− larvae exhibited a significant increase in the amount and proportion of first feeding, and their growth rate significantly exceeded that of wild-type controls during the week after feeding. This observation suggests that although the development of the retina may be somewhat affected, thrb2−/− larvae show positive changes in feeding behaviour and growth rate, which may be related to their enhanced ability to adapt to their environment. These results provide novel insights into the function of the thrb2 gene in the visual system and behaviour and may have implications in areas such as fish farming and genetic improvement. Full article
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19 pages, 605 KiB  
Systematic Review
Retinal and Choroidal Alterations in Thyroid-Associated Ophthalmopathy: A Systematic Review
by Alexandra Magdalena Ioana, Diana Andrei, Daniela Iacob and Sorin Lucian Bolintineanu
Life 2025, 15(2), 293; https://doi.org/10.3390/life15020293 - 13 Feb 2025
Cited by 2 | Viewed by 984
Abstract
Thyroid-associated ophthalmopathy (TAO), or Graves’ orbitopathy (GO), is a complex autoimmune disorder affecting orbital tissues, often leading to vision-threatening complications such as dysthyroid optic neuropathy (DON). In this systematic review, conducted following PRISMA guidelines, 22 studies were evaluated to investigate the role of [...] Read more.
Thyroid-associated ophthalmopathy (TAO), or Graves’ orbitopathy (GO), is a complex autoimmune disorder affecting orbital tissues, often leading to vision-threatening complications such as dysthyroid optic neuropathy (DON). In this systematic review, conducted following PRISMA guidelines, 22 studies were evaluated to investigate the role of optical coherence tomography (OCT) in assessing retinal and choroidal changes in TAO. Parameters such as the retinal nerve fiber layer (RNFL), ganglion cell complex (GCC), ganglion cell layer (GCL), and choroidal thickness were analyzed. RNFL changes varied by disease severity, with significant thinning in DON due to nerve fiber loss and thickening in early DON due to optic disk edema. Subfoveal choroidal thickness (SFCT) was consistently higher in active TAO, correlating positively with the clinical activity score (CAS) and proptosis, suggesting its role as a marker of disease activity. Subgroup analysis revealed that spectral-domain OCT (SD-OCT) was the most sensitive for detecting retinal changes. The findings highlight the effectiveness of OCT in detecting minor retinal and choroidal alterations in TAO. However, the variability of study designs, as well as the lack of longitudinal data, limits the ability to draw broad conclusions. Further standardized, long-term investigations are required to properly understand OCT’s diagnostic and prognostic value in TAO. Full article
(This article belongs to the Special Issue Eye Diseases: Diagnosis and Treatment, 3rd Edition)
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13 pages, 1041 KiB  
Article
Quantitative Analysis of Early Retinal Changes and OCT Parameters in Diabetic Subjects with and Without Retinopathy
by Sulaiman Aldakhil, Naveen Challa, Saja A. Alhoshan, Foziyah Abohaimed, Bashair N. Alnasser, Hana A. Almuhawas, Saif AlObaisi and Saif H. Alrasheed
Diagnostics 2025, 15(4), 451; https://doi.org/10.3390/diagnostics15040451 - 13 Feb 2025
Viewed by 987
Abstract
Aim: The aim of this paper is to assess the changes in optical coherence tomography angiography (OCTA) parameters among normal individuals and for type 2 diabetes mellitus (DM) patients, with and without retinopathy, in the adult Saudi population. Methods: This was a [...] Read more.
Aim: The aim of this paper is to assess the changes in optical coherence tomography angiography (OCTA) parameters among normal individuals and for type 2 diabetes mellitus (DM) patients, with and without retinopathy, in the adult Saudi population. Methods: This was a prospective cross-sectional study; subjects were divided into four groups. Group 1, the control group, consisted of 40 eyes from normal healthy individuals, while the other three groups included subjects diagnosed with type 2 DM at various stages of retinopathy. All subjects’ OCT and OCTA images were acquired using a swept-source OCT (DRI Triton, Topcon, Inc., Tokyo, Japan). Parameters collected included superficial capillary plexus (SCP) vessel density (VD), foveal avascular zone (FAZ), macular thickness (MT), ganglion cell layer (GCL) thickness, and retinal nerve fiber layer (RNFL) thickness at central and perifoveal locations. OCTA acquisition included a 4.5 × 4.5 mm scan to measure FAZ and SCP VD, with the FAZ manually mapped onto OCTA images at the SCP. Results: There was a significant decrease in SCP VD (p < 0.05) in all quadrants except the central as the severity of diabetes increased. SCP VD was considerably lower in DM patients without retinopathy compared to controls. Additionally, the FAZ area exhibited a significant increasing trend as the severity of diabetic retinopathy (DR) increased. Regression analysis showed a significant decrease in RNFL thickness (p < 0.01) and GCL thickness (p < 0.01) in the nasal quadrant as DR severity increased, even after adjusting for age, gender, and mean arterial pressure. Furthermore, SCP VD showed a significant negative correlation with both the duration of DM and contrast sensitivity. Conclusions: OCT and OCTA parameters were significantly different between the control and diabetic patients with and without DR. The observed microvascular and contrast sensitivity alterations may precede detectable DR damage or changes in visual acuity. Full article
(This article belongs to the Special Issue Visual Impairment: Diagnosis and Management)
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17 pages, 2583 KiB  
Article
A Neuroprotective Peptide Modulates Retinal cAMP Response Element-Binding Protein (CREB), Synapsin I (SYN1), and Growth-Associated Protein 43 (GAP43) in Rats with Silicone Oil-Induced Ocular Hypertension
by Gretchen A. Johnson, Raghu R. Krishnamoorthy, Ram H. Nagaraj and Dorota L. Stankowska
Biomolecules 2025, 15(2), 219; https://doi.org/10.3390/biom15020219 - 3 Feb 2025
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Abstract
This study evaluated the neuroprotective potential of peptain-1 conjugated to a cell-penetrating peptide (CPP-P1) in an ocular hypertension model of glaucoma. Brown Norway (BN) rats were subjected to intraocular pressure (IOP) elevation via intracameral injection of silicone oil (SO), with concurrent intravitreal injections [...] Read more.
This study evaluated the neuroprotective potential of peptain-1 conjugated to a cell-penetrating peptide (CPP-P1) in an ocular hypertension model of glaucoma. Brown Norway (BN) rats were subjected to intraocular pressure (IOP) elevation via intracameral injection of silicone oil (SO), with concurrent intravitreal injections of either CPP-P1 or a vehicle. Retinal cross-sections were analyzed for markers of neuroprotection, including cAMP response element-binding protein (CREB), phosphorylated CREB (p-CREB), growth-associated protein-43 (GAP43), synapsin-1 (SYN1), and superoxide dismutase 2 (SOD2). Hematoxylin and eosin staining was used to assess retinal-layer thickness. SO-treated rats exhibited significant reductions in the thickness of the inner nuclear layer (INL, 41%, p = 0.016), inner plexiform layer (IPL, 52%, p = 0.0002), and ganglion cell layer (GCL, 57%, p = 0.001). CPP-P1 treatment mitigated these reductions, preserving INL thickness by 32% (p = 0.059), IPL by 19% (p = 0.119), and GCL by 31% (p = 0.057). Increased levels of CREB (p = 0.17) and p-CREB (p = 0.04) were observed in IOP-elevated, CPP-P1-treated retinas compared to IOP-elevated, vehicle-treated retinas. Although overall GAP43 levels were low, there was a modest increase in expression within the IPL and GCL in SO- and CPP-P1-treated retinas (p = 0.15 and p = 0.09, respectively) compared to SO- and vehicle-treated retinas. SO injection reduced SYN1 expression in both IPL and GCL (p = 0.01), whereas CPP-P1 treatment significantly increased SYN1 levels in the IPL (p = 0.03) and GCL (p = 0.002). While SOD2 expression in the GCL was minimal across all groups, a trend toward increased expression was observed in CPP-P1-treated animals (p = 0.16). The SO model was replicated with SO removal after 7 days and monitored for 21 days followed by retinal flat-mount preparation to assess retinal ganglion cell (RGC) survival. A 42% loss in RGCs (p = 0.009) was observed in SO-injected eyes, which were reduced by approximately 37% (p = 0.03) with CPP-P1 treatment. These findings suggest that CPP-P1 is a promising neuroprotective agent that promotes retinal ganglion cell survival and the preservation of other retinal neurons, potentially through enhanced CREB signaling in a rat model of SO-induced ocular hypertension. Full article
(This article belongs to the Special Issue Retinal Diseases: Molecular Mechanisms and Therapies)
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17 pages, 2031 KiB  
Article
Dysfunction and Morphological Involvement of Inner Macular Layers in Glaucoma
by Vincenzo Parisi, Lucia Ziccardi, Sara Giammaria, Lucilla Barbano, Lucia Tanga, Manuele Michelessi, Gloria Roberti, Carmela Carnevale, Carmen Dell’Aquila, Mattia D’Andrea, Gianluca Manni and Francesco Oddone
J. Clin. Med. 2024, 13(22), 6882; https://doi.org/10.3390/jcm13226882 - 15 Nov 2024
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Abstract
Objectives: This study aimed to study the inner retina functional and morphological impairment of retinal ganglion cells (RGCs) from specific macular rings and sectors to identify whether selective macular regions were more vulnerable than others within the 20 central degrees in patients with [...] Read more.
Objectives: This study aimed to study the inner retina functional and morphological impairment of retinal ganglion cells (RGCs) from specific macular rings and sectors to identify whether selective macular regions were more vulnerable than others within the 20 central degrees in patients with open-angle glaucoma (OAG). Methods: In total, 21 OAG patients [mean age 50.19 ± 7.86 years, Humphrey Field Analyzer (HFA) 24-2 mean deviation (MD) between −5.02 and −22.38 dB, HFA 10-2 MD between −3.07 and −17.38 dB], providing 21 eyes, were enrolled in this retrospective case–control study. And 20 age-similar healthy subjects, providing 20 eyes, served as controls. The multifocal photopic negative response (mfPhNR) response amplitude density (RAD) from concentric rings and macular sectors and ganglion cell layer thickness (GCL-T) assessed by Spectral Domain–Optical Coherence Tomography (SD-OCT) was measured. Mean RAD and GCL-T values were compared between OAG and control ones by ANOVA. In OAG eyes, the relationship between mfPhNR and SD-OCT data was examined by linear regression analysis, and Pearson’s correlation coefficients were computed. Results: In considering all rings and sectors, compared to the controls, the OAG group showed a significant (p < 0.01) reduction in mean mfPhNR RAD and in GCL-T values with the greatest reduction in the central area. In OAG eyes, a significant (p < 0.01) correlation between all mfPhNR RAD and GCL-T values, with significant (p < 0.01) correlation coefficients, were found. Conclusions: In OAG eyes, RGC dysfunction was detectable by abnormal mfPhNR responses in localized macular areas, mainly in the central one. Localized macular RGC dysfunction was linearly correlated with the GCL morphological changes. Full article
(This article belongs to the Special Issue Diagnosis, Treatment, and Prevention of Glaucoma: Second Edition)
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14 pages, 602 KiB  
Article
Evaluation of Retinal and Posterior Segment Vascular Changes Due to Systemic Hypoxia Using Optical Coherence Tomography Angiography
by Nadav Levinger, Nir Erdinest, Ayman Abu Rmeileh, Eisa Mouallem, Shadi Zahran, Sheer Shabat, Yotam Kolben, Talmon Aviv, Rottem Kuint, Liran Tiosano and Samer Khateb
J. Clin. Med. 2024, 13(22), 6680; https://doi.org/10.3390/jcm13226680 - 7 Nov 2024
Viewed by 1055
Abstract
Background/Objectives: Retinal vascular occlusions are a significant cause of visual impairment in older adults, resulting in ischemic retinal damage and sudden vision loss. This study evaluates the retinal, optic nerve head (ONH), and choroidal capillary networks in chronic and acute-on-chronic hypoxia compared to [...] Read more.
Background/Objectives: Retinal vascular occlusions are a significant cause of visual impairment in older adults, resulting in ischemic retinal damage and sudden vision loss. This study evaluates the retinal, optic nerve head (ONH), and choroidal capillary networks in chronic and acute-on-chronic hypoxia compared to normal controls using optical coherence tomography angiography (OCT-A). Methods: We evaluated a prospective study including twenty patients in the hypoxic group (mean age 61.2 ± 10.2) in two phases, chronic hypoxia and acute-on-chronic hypoxia, and 21 control subjects (mean age 59 ± 9.4 years). All patients underwent a comprehensive eye examination, OCT, and OCT-A imaging. The data were analyzed using OCT-A analysis software (Zeiss OCT-A software 2.1.0.55513) and Fiji software (1.51a). Vascular density of the retina and ONH, choriocapillaries, and foveal avascular zone (FAZ) size were measured. Results: The superficial peripapillary vascular density was higher for the control group (0.387 ± 0.03) compared to the hypoxic patients with (0.383 ± 0.03) and without O2 supplementation (0.383 ± 0.03; p = 0.018). No retinal angiographic differences were identified between the two study groups. The ganglion cell layer (GCL) was thinner in the hypoxic group. Both hypoxic subgroups demonstrated denser choriocapillaries (mean 13,073 ± 1812 and 12,689 ± 1815, with and without O2 supplementation, respectively) compared to the control group (mean 9749 ± 2881, p < 0.001 for both groups). Hypoxic patients demonstrated increased area size of choriocapillaries (+O2 supplementation—mean 44,347 ± 10,563; −O2 supplementation—mean 46,984 ± 12,822) compared to the control group (mean 30,979 ± 9635; p < 0.01 and p < 0.001, respectively). Conclusions: Chronic and acute-on-chronic hypoxia did not affect the retinal vascular network, most probably due to the strong autoregulation of vascular function of the retina. However, compared to the control group, GCL, ONH vasculature density, and most choriocapillaries indices were significantly altered among hypoxic patients. Full article
(This article belongs to the Section Ophthalmology)
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