Search Results (311)

The pituitary adenylate cyclase-activating polypeptide receptor 1 (PAC1) plays a pivotal role in central nervous system development and homeostasis. Comparisons of PAC1 knockout (PAC1^−/−), heterozygous (PAC1^+/−) and wild-type (PAC1^+/+) mice demonstrate that PAC1 deficiency severely impairs pre-weaning survival and results in marked developmental deficits, including reduced postnatal weight and altered locomotor behavior. PAC1^−/− mice exhibited hyperlocomotion, reduced anxiety-like behavior, and transient deficits in motor coordination. Gene expression analyses revealed widespread dysregulation of oligodendrocyte-associated markers, with significant myelin reduction and decreased mature oligodendrocyte density in the corpus callosum. ER stress was evidenced in both white matter and motor cortex, as indicated by altered expression of UPR-related genes and increased phosphorylated (p)IRE1⁺ neurons. Retinal morphology was compromised in PAC1^−/− animals, with reduced overall retinal and ganglion cell layer thickness. Notably, no gross morphological or molecular abnormalities were detected in the spinal cord regarding myelin content or MBP expression; however, synaptic marker expression was selectively reduced in the ventral horn of PAC1-deficient mice. Together, these findings highlight a critical role for PAC1 in oligodendrocyte maturation, retinal development, and synaptogenesis, providing new insights with relevance in multiple sclerosis and other neurodevelopmental and neurodegenerative conditions. Full article

Blue-light stimulation of the optic disc has been suggested as a means of myopia prevention by activating dopaminergic amacrine cells via intrinsically photosensitive retinal ganglion cells. This prospective, adequately powered study investigated this approach by examining its effects on pattern electroretinogram (PERG) N95 amplitude and choroidal thickness (ChT), established biomarkers associated with retinal ganglion cell function and myopia progression, respectively. Forty-six healthy adults received one minute of 450 nm blue-light stimulation to either the optic disc or central retina of the right eye, with the fellow left eye serving as control. PERG responses were measured before and 20 min after stimulation (N = 15 per stimulation location), while ChT, using swept-source optical coherence tomography images, was measured before, 20, and 60 min after stimulation (N = 8 per stimulation location). Only retinal stimulation significantly increased PERG N95 amplitude (baseline 16.16 µV, post-stimulation 17.61 µV [p = 0.01]), whereas optic disc stimulation did not (baseline 18.71 µV, post-stimulation 18.81 µV [p = 0.76]). Neither optic disc nor retinal stimulation significantly changed ChT at any time point. No significant differences were observed between myopic and non-myopic participants. Our findings do not support the hypothesis that short-duration blue-light stimulation of the optic disc is a viable strategy to activate retinal dopaminergic pathways for myopia prevention. Full article

Our study explored the role of serum 25-hydroxyvitamin D [25(OH)D] levels as an indicator of response to intravitreal anti–vascular endothelial growth factor (anti-VEGF) therapy in patients with diabetic macular edema (DME), highlighting functional and anatomical outcomes linked to systemic biomarker profiles. In a cohort of treatment-naive diabetic patients, vitamin D status was correlated with post-treatment changes in central macular thickness (CMT) and best-corrected visual acuity (BCVA), illustrating layered therapeutic responses among deficient, insufficient, and sufficient vitamin D groups. Functional gains, measured as improvements in decimal BCVA, and anatomical improvements, defined by CMT reduction via spectral-domain optical coherence tomography (SD-OCT), were primarily detected in patients with sufficient vitamin D levels. Remarkably, patients with serum 25(OH)D ≥ 30 ng/mL revealed complete dual-response rates, while those in the deficient group manifested partial therapeutic efficacy, supporting the immunoangiogenic modulatory role of vitamin D. Statistical associations exposed a tight linear connection between baseline and final visual acuity and a pronounced inverse relationship between CMT and final vision, suggesting that vitamin D may play a role in treatment-mediated structural recovery. These results may imply that low vitamin D levels lead to subclinical endothelial dysfunction and impaired retinal barrier repair, possibly through dysregulated anti–vascular endothelial growth factor (anti-VEGF) signaling, chronic inflammation, and oxidative stress. Our findings underscore the need for and importance of further research of vitamin D status as an adjunctive biomarker in the clinical approach of personalized DME and validates the potential of circulating vitamin D evaluation in therapeutic classification and predictive eye care. Full article

Background: Optic neuritis (ON) is a common manifestation of multiple sclerosis (MS), serving as a clinical window into central nervous system demyelination. Optical coherence tomography (OCT) and visual evoked potentials (VEPs) are complementary non-invasive tools for assessing structural and functional damage to the visual pathway. The objective of this paper is to evaluate correlations between OCT and VEP parameters in MS patients with and without a history of ON and assess their relationship with disease duration and disability (EDSS). Methods: This cross-sectional study included 54 eyes from 27 relapsing–remitting MS patients. OCT was used to measure circumpapillary and the temporal peripapillary retinal nerve fiber layer (pRNFL) and the foveal/parafoveal ganglion cell-inner plexiform layer (GCIPL) thickness. VEPs assessed P100 latency and amplitude. Patients were grouped by ON history. Results: Eyes without ON showed a significantly greater circumpapillary pRNFL thickness (mean difference: 18.27 ± 5.33 µm, p = 0.001), temporal pRNFL thickness (15.71 ± 5.49 µm, p = 0.006), and parafoveal GCIPL thickness (12.85 ± 5.3 µm, p = 0.019) compared to ON eyes. p100 latency was shorter and the amplitude was higher in NON eyes, but without statistical significance. Strong negative correlations were found between OCT thickness and EDSS and disease duration. p100 latency correlated negatively with OCT parameters, while amplitude showed a positive correlation with pRNFL thickness in ON eyes. Conclusions: OCT parameters, particularly pRNFL and GCIPL thickness, correlate with functional and clinical markers of MS. Combined OCT–VEP evaluation enhances the assessment of neurodegeneration and disease progression. Full article

Background/Objectives: The aim of this study was to evaluate the relationship between foveal avascular zone (FAZ) enlargement, retinal ganglion cell (RGC) dysfunction, and structural retinal measurements in glaucoma suspects (GS), using pattern electroretinogram (PERG) and optical coherence tomography angiography (OCTA) parameters. Methods: Thirty-one eyes (20 subjects) of GS status underwent comprehensive ophthalmologic evaluation including steady-state PERG, optical coherence tomography (OCT), and OCTA. FAZ area was measured using ImageJ software (version 1.54p), and PERG parameters (Magnitude, MagnitudeD, and MagnitudeD/Magnitude ratio) were analyzed. Partial correlation analyses were performed to assess associations between FAZ area, PERG parameters, and structural metrics including retinal nerve fiber layer (RNFL), ganglion cell layer–inner plexiform layer (GCL + IPL), and macular thickness. Results: After controlling for age, sex, central corneal thickness (CCT), intraocular pressure (IOP), and spherical equivalent, partial correlation analysis showed that FAZ area was significantly associated with both lower Magnitude (r < −0.503, p < 0.05) and MagnitudeD (r < −0.507, p < 0.05) values. PERG parameters were significantly correlated with superior and average RNFL thickness, as well as superior and superior temporal GCL + IPL thickness. FAZ area was significantly associated with multiple GCL + IPL and macular thickness sectors, but not with RNFL thickness. Conclusions: FAZ enlargement is significantly associated with RGC dysfunction and inner retinal layer thinning in GS. Full article

Background: Obstructive sleep apnea (OSA) is increasingly recognized as a potential risk factor for glaucoma due to its association with intermittent hypoxia and vascular dysregulation. The aim of this study was to investigate early glaucomatous changes in the eyes of patients with OSA. Methods: This case–control study included 25 patients with OSA and 25 age- and sex-matched healthy controls. According to the STOP-Bang Questionnaire, patients with an intermediate or severe risk of OSA underwent polysomnography. Based on the apnea-hypopnea index, only patients with severe OSA were included in the study group. All participants underwent a full ophthalmological examination, with measurements of the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness performed using optical coherence tomography (OCT). Results: Statistical comparisons revealed that intraocular pressure (IOP) was slightly elevated, while central corneal thickness (CCT) was slightly reduced in patients with OSA compared to healthy controls. OCT measurements showed an overall reduction in both RNFL and GCL thicknesses in the OSA group. Among these findings, only the differences in average and minimum GCL thickness in the left eye reached statistical significance. Conclusions: The results of our study indicate significant thinning of the GCL in patients with OSA, suggesting possible early glaucomatous changes and a potential link between OSA and glaucoma. Given the increasing prevalence of OSA, further large-scale, long-term studies are needed to better understand this relationship and its clinical implications. Full article

Background/Objectives: Attention deficit hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder. As the retina is an extension of the central nervous system, retinal imaging may provide insights into the ADHD pathophysiology. The objective of this work was to evaluate structural retinal alterations using optical coherence tomography (OCT) in ADHD patients compared to neurotypical controls. Methods: A case–control study involving 200 eyes (100 from 50 patients with ADHD and 100 from 50 controls) was conducted by comparing the thicknesses of the macular region (total retina, inner and outer retinal layers, ganglion cell layer plus inner plexiform layer [GCIPL], and macular retinal nerve fiber layer [mRNFL]), the peripapillary region (pRNFL), and the optic nerve head (ONH) parameters. Areas under the curve (AUCs) were calculated to evaluate diagnostic performance. Right and left eyes were analyzed separately. Results: Patients with ADHD showed a significant reduction in total and outer retinal thickness across several macular sectors in both eyes. No significant differences were observed in mRNFL, GCIPL, inner retina, pRNFL, or ONH parameters between groups. AUC values derived from ROC analysis indicate moderate diagnostic performance for total and outer retinal thickness in the macular region. Conclusions: ADHD is associated with retinal thinning in the macula (total and outer retinal thickness) in both eyes, suggesting the potential of OCT-based biomarkers for this condition. Full article

Objectives: This study aimed to evaluate the 6-month real-world outcomes of switching to faricimab in patients with aflibercept-resistant neovascular age-related macular degeneration (nAMD). Methods: A retrospective review was conducted on the eyes of 60 patients with aflibercept-resistant nAMD that were switched to faricimab. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters, including central subfield thickness (CST), subfoveal choroidal thickness (SFCT), and both the maximum height and width of pigment epithelial detachment (PED), at baseline and 1, 3, and 6 months after switching were evaluated. The type of PED and retinal fluid were also analyzed. Results: The results showed that BCVA remained stable at month 6 (p = 0.150), while CST significantly decreased (p = 0.020), and SFCT remained unchanged (p = 0.072). The maximum PED height significantly decreased (p = 0.030), while the maximum PED width did not change (p = 0.07). The mean injection interval significantly increased from 6.8 ± 2.4 weeks before switching to 11.2 ± 1.7 weeks after switching (p = 0.068). Furthermore, the dry macula rate was 43.3% at month 6. Conclusions: Switching to faricimab in aflibercept-resistant nAMD patients showed stable visual outcomes, significant anatomical improvements, and reduced treatment burden over 6 months in real-world clinical settings. Full article

Background: In clinical practice, visual outcomes with anti-VEGF therapy may be worse than those observed in clinical trials. In this study, we aim to investigate the long-term outcomes of neovascularization treated with intravitreal aflibercept injections (IAI) in a teaching hospital setting. Methods: This is a retrospective, single-center study including 81 nAMD patients (116 eyes), those both newly diagnosed and switched from ranibizumab. All patients had a follow-up duration of at least seven years. Treatment involved three monthly injections followed by either a pro re nata (PRN) or treat and extend regimen. Follow-up care was primarily conducted by training physicians. The primary endpoint was the change in best-corrected visual acuity (BCVA) over seven years. Secondary endpoints included central retinal thickness changes, qualitative OCT parameters, macular atrophy progression, injection frequency, and treatment adherence. Results: Among the 116 eyes, 52 (44.8%) completed the seven-year follow-up. Visual acuity improved by +2.1 letters in the overall population (+6.3 letters in treatment-naive eyes) after the loading phase but gradually declined, resulting in a loss of −12.3 letters at seven years. BCVA remained stable (a loss of fewer than 15 letters) in 57.7% of eyes. Central retinal thickness (CRT) decreased significantly during follow-up in both naive and switcher eyes. Macular atrophy occurred in 94.2% of eyes, progressing from 1.42 mm² to 8.55 mm² over seven years (p < 0.001). The mean number of injections was 4.1 ± 1.8 during the first year and 3.7 per year thereafter. Advanced age at diagnosis was a risk factor for loss to follow-up, with bilaterality being a protective factor against loss to follow-up (p < 0.05). Conclusions: This study highlights the challenges faced by a retina clinic in a teaching hospital. Suboptimal functional and anatomical outcomes in real life may derive from insufficient patient information and inconsistent monitoring, which contributes to undertreatment and affects long-term visual outcomes. It also raises concerns about supervision in a teaching hospital which needs to be improved. Full article

Background/Objectives: To identify the predictive biomarkers of treatment response following a switch to brolucizumab in patients with aflibercept-refractory neovascular age-related macular degeneration (nAMD). Methods: This retrospective study included 47 eyes of 44 patients with nAMD who were switched to brolucizumab; a two-year follow-up was completed for 37 eyes of 34 patients after the switch. The patients were classified into two groups based on the presence (fluid group) or absence (dry group) of retinal fluid at one and two years after switching, and their visual acuity, central retinal thickness, subfoveal choroidal thickness, injection interval, and dry macular rate were evaluated. Results: A dry macula was achieved for approximately 80% of patients at two years after the switch (p < 0.001), and the mean injection interval was significantly extended from 6.4 ± 1.8 weeks to 10.5 ± 2.6 weeks during the same period (p < 0.001). Both the mean central retinal thickness and subfoveal choroidal thickness showed a significant decrease at two years after the switch (p < 0.001 for both). A significantly higher proportion of patients in the Dry group exhibited punctate hyperfluorescence in the fellow eye (p < 0.001), and all patients in the dry group achieved a dry macula at two years. Conclusions: Switching to brolucizumab may be an effective treatment option for patients with aflibercept-refractory nAMD. Punctate hyperfluorescence may serve as a favorable prognostic factor following a switch to brolucizumab. Full article

Background: Secondary epiretinal membrane (ERM) is a common complication of diabetic retinopathy, but data on surgical outcome is limited. The aim of this study was to evaluate anatomical and functional outcomes after pars plana vitrectomy with ERM peeling in eyes with diabetic retinopathy. Methods: A retrospective analysis was conducted on 87 eyes of 87 consecutive patients with diabetic retinopathy who underwent ERM peeling over a ten-year period (04/2013–11/2022). Collected data included demographics, best-corrected visual acuity (BCVA), stage of diabetic retinopathy, and optical coherence tomography parameters such as central subfield retinal thickness (CSRT), macular volume (MV), and presence of hyperreflective foci, subretinal fluid, and intraretinal fluid. Statistical analyses were performed using a paired t-test and the Wilcoxon test. Results: The majority of patients had type 2 diabetes (96.6%), and 69.0% presented with diabetic macular edema (DME). The mean follow-up was 2.2 ± 2.0 years. Significant postoperative reductions were observed in CSRT (from 377.20 ± 99.28 µm to 337.99 ± 113.834 µm; p = 0.008) and MV (from 10.11 ± 1.46 mm³ to 99.28 ± 1.07 mm³; p < 0.001). No significant changes in BCVA were observed across the entire study cohort. ERM recurrence was rare (2.3%), and no major complications occurred. Conclusions: ERM peeling in diabetic eyes leads to significant anatomical improvement, especially in advanced diabetic retinopathy and DME, but with limited functional gains. The surgical indication should be carefully considered. Full article

Background/Objectives: To investigate the effect of ellipsoid zone (EZ) integrity and retinal fluid on best-corrected visual acuity (BCVA) in neovascular, age-related macular degeneration. Methods: This was a post hoc treatment-agnostic analysis of the phase 3 HAWK trial. Intraretinal fluid (IRF), subretinal fluid (SRF), and ellipsoid zone (EZ) integrity were quantified over 48 weeks. EZ integrity maintenance was defined as EZ-RPE central subfield thickness (CST) >20 µm; partial EZ attenuation was EZ-RPE CST >0 and ≤20 µm; total EZ attenuation was EZ-RPE CST = 0 µm. Results: During treatment, BCVA in eyes with no fluid (66.5 to 70.2 letters) was greater than in eyes with IRF (59.5 to 62.4 letters) but comparable to BCVA in eyes with SRF (64.9 to 68.8 letters). In eyes with no fluid, BCVA was consistently greater in eyes with EZ integrity maintained (73.4 to 78.4 letters) than in eyes with EZ partial attenuation (65.3 to 66.5 letters) or with EZ total attenuation (55.8 to 59.8 letters). Conclusions: Eyes without fluid with EZ preservation achieved the highest overall BCVA, especially when compared to eyes without fluid and a lack of EZ preservation and to eyes with SRF. Achieving a “dry” status with preservation of EZ integrity is important in optimizing visual outcomes. Full article

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

Purpose: This study aims to evaluate the clinical utility of a prototype ultra-widefield (UWF) single-capture optical coherence tomography (OCT) lens developed to image large areas of the retina. Material and Methods: This study included OCT and angio-OCT measurements performed with a REVO FC 130 (Optopol Technology, Poland) with an add-on widefield lens in a case series of 215 patients with retinal pathologies and 39 healthy subjects. The imaging width provided by the lens was 22 mm (covering a 110-degree field of view), while the scanning window height ranged from 2.8 to 6 mm. Results: The quality of the peripheral UWF OCT and angio-OCT images obtained by REVO FC 130 with the attachable lens is very good and sufficient for patient diagnosis, follow-up, and treatment planning. Both the boundaries of the non-perfusion zones and the location and extent of vascular proliferations can be accurately traced. Furthermore, the vitreoretinal interface can also be accurately assessed over a large area. The imaging quality of the macula with UWF OCT angiography is also good. The mean thickness measurement difference between a UWF and a standard 10 mm 3D retinal scan in a healthy individuals for the Central ETDRS sector was −1.37 ± 2.96 µm (the 95% limits of agreement (LoA) on Bland–Altman plots ranged from −6.82 to 2.43); for the Inferior Inner sector, it was −2.81 ± 1.09 µm (95% LoA, −4.94 to −0.68); for the Inferior Outer sector, it was −1.31 ± 2.58 µm (95% LoA, −6.38 to 3.75); for the Nasal Inner sector: −1.46 ± 1.19 µm (95% LoA, −3.79 to 0.88); for the Nasal Outer sector, it was −0.56 ± 2.61 µm (95% LoA, −5.67 to 4.55); for the Superior Inner sector, it was −2.71 ± 3.16 µm (95% LoA, −8.91 to 3.48); for the Superior Outer sector, it was −1.82 ± 1.39 µm (95% LoA, −4.55 to 0.91); for the Temporal Inner sector, it was −1.77 ± 2.24 µm (95% LoA, −6.16 to 2.62); for the Temporal Outer sector, it was −3.61 ± 1.43 µm (95% LoA, −6.41 to −0.81). Discussion: The proposed method of obtaining UWF OCT and UWF angio-OCT images using an add-on lens with the REVO FC 130 gives high-quality scans over the entire 110-degree field of view. This study also shows a high agreement of the ETDRS sector’s thickness measurements between UWF and standard retinal scans, which allows UWF to be used for quantitative macular thickness analysis. Considering its image quality, simplicity, and reliability, an add-on lens can be successfully used for the UWF OCT and OCT angiography evaluation of the retina on a daily basis. Full article

Purpose: Varicella zoster virus (VZV) vasculopathy can occur in patients with herpes zoster (HZ). Our aim was to evaluate the retinal microvascular vessel density (VD) in patients with trigeminal HZ measured by optical coherence tomography angiography (OCTA). Methods: 48 eyes of 24 patients with HZ and 48 eyes of 24 healthy age- and gender-matched controls were included in this study. All participants underwent an OCTA examination using RTVue XR Avanti with AngioVue. The VD data of the macular 3 × 3 mm OCT angiogram of the superficial capillary plexus (SCP), the deep capillary plexus (DCP), and the choriocapillaris (CC) as well as the VD data of the optic nerve head (ONH) were extracted and analyzed. Results: The VD in the SCP, DCP, and CC of patients with HZ was significantly lower compared with healthy controls (p < 0.05). Equally, there was a noticeable reduction in the inside disk area of the ONH. There was no statistically noticeable reduction in the FAZ area and central retinal thickness. Conclusions: In this study, HZ patients demonstrated a decrease in the retinal VD of the SCP, DCP, ONH, and the CC. Quantitative analysis of retinal perfusion using OCTA may therefore help in the diagnosis and monitoring of HZ. Further studies must show to what extent this may be an indication of VZV-related vasculopathy and whether OCTA data can be used as a biomarker in these patients in the future. Full article