Explore the vast range of titles available.

The present narrative review reports the main preclinical and clinical results obtained by using supplementation of saffron or its pure components in neurodegeneration, with special emphasis on age-related macular degeneration. Beyond that, this article will address shared pathways between neurodegenerative diseases of the eye and the brain. It will be shown that saffron treatment might counteract oxidative damage in the retina and brain, as well as inflammation and inflammatory mediators that induce neuronal degeneration and death. The ways of action are multiple, and saffron chemical components appear to act in a synergistic manner, inducing tissue resilience. These effects critically depend upon the saffron chemical composition and structure. A well-defined ratio among molecules is linked to a patented batch known as Repron® and offers the maximum protection against neurodegeneration.

A new system based on binary Deep Learning (DL) convolutional neural networks has been developed to recognize specific retinal abnormality signs on Optical Coherence Tomography (OCT) images useful for clinical practice. Images from the local hospital database were retrospectively selected from 2017 to 2022. Images were labeled by two retinal specialists and included central fovea cross-section OCTs. Nine models were developed using the Visual Geometry Group 16 architecture to distinguish healthy versus abnormal retinas and to identify eight different retinal abnormality signs. A total of 21,500 OCT images were screened, and 10,770 central fovea cross-section OCTs were included in the study. The system achieved high accuracy in identifying healthy retinas and specific pathological signs, ranging from 93 to 99%. Accurately detecting abnormal retinal signs from OCT images is crucial for patient care. This study aimed to identify specific signs related to retinal pathologies, aiding ophthalmologists in diagnosis. The high-accuracy system identified healthy retinas and pathological signs, making it a useful diagnostic aid. Labelled OCT images remain a challenge, but our approach reduces dataset creation time and shows DL models’ potential to improve ocular pathology diagnosis and clinical decision-making.

The use of deep learning for OCT image classification could enhance the diagnosis and monitoring of retinal diseases. However, challenges like variability in retinal abnormalities, noise, and artifacts in OCT images limit its clinical use. Our study aimed to evaluate the performance of various deep learning (DL) architectures in classifying retinal pathologies versus healthy cases based on OCT images, under data scarcity and label noise. We examined five DL architectures: ResNet18, ResNet34, ResNet50, VGG16, and InceptionV3. Fine-tuning of the pre-trained models was conducted on 5526 OCT images and reduced subsets down to 21 images to evaluate performance under data scarcity. The performance of models fine-tuned on subsets with label noise levels of 10%, 15%, and 20% was evaluated. All DL architectures achieved high classification accuracy (> 90%) with training sets of 345 or more images. InceptionV3 achieved the highest classification accuracy (99%) when trained on the entire training set. However, classification accuracy decreased and variability increased as sample size decreased. Label noise significantly affected model accuracy. Compensating for labeling errors of 10%, 15%, and 20% requires approximately 4, 9, and 14 times more images in the training set to reach the performance of 345 correctly labeled images. The results showed that DL models fine-tuned on sets of 345 or more OCT images can accurately classify retinal pathologies versus healthy controls. Our findings highlight that while mislabeling errors significantly impact classification performance in OCT analysis, this can be effectively mitigated by increasing the training sample size. By addressing data scarcity and labeling errors, our research aims to improve the real-world application and accuracy of retinal disease management.

Strategies aimed at invoking synaptic plasticity have therapeutic potential for several neurological conditions. The human retinal synaptic disease X-linked retinoschisis (XLRS) is characterized by impaired visual signal transmission through the retina and progressive visual acuity loss, and mice lacking retinoschisin (RS1) recapitulate human disease. Here, we demonstrate that restoration of RS1 via retina-specific delivery of adeno-associated virus type 8-RS1 (AAV8-RS1) vector rescues molecular pathology at the photoreceptor-depolarizing bipolar cell (photoreceptor-DBC) synapse and restores function in adult Rs1-KO animals. Initial development of the photoreceptor-DBC synapse was normal in the Rs1-KO retina; however, the metabotropic glutamate receptor 6/transient receptor potential melastatin subfamily M member 1-signaling (mGluR6/TRPM1-signaling) cascade was not properly maintained. Specifically, the TRPM1 channel and G proteins Gαo, Gβ5, and RGS11 were progressively lost from postsynaptic DBC dendritic tips, whereas the mGluR6 receptor and RGS7 maintained proper synaptic position. This postsynaptic disruption differed from other murine night-blindness models with an electronegative electroretinogram response, which is also characteristic of murine and human XLRS disease. Upon AAV8-RS1 gene transfer to the retina of adult XLRS mice, TRPM1 and the signaling molecules returned to their proper dendritic tip location, and the DBC resting membrane potential was restored. These findings provide insight into the molecular plasticity of a critical synapse in the visual system and demonstrate potential therapeutic avenues for some diseases involving synaptic pathology.

Optical coherence tomography (OCT) is widely used to probe retinal structure and function. This study investigated the outer retina band (ORB) pattern and reflective intensity for the region between bands 2 and 3 (Dip) in three mouse models of inherited retinal degeneration (Rs1KO, TTLL5KO, RPE65KO) and in human AMD patients from the A2A database. OCT images were manually graded, and reflectivity signals were used to calculate the Dip ratio. Qualitative analyses demonstrated the progressive merging band 2 and band 3 in all three mouse models, leading to a reduction in the Dip ratio compared to wildtype (WT) controls. Gene replacement therapy in Rs1KO mice reverted the ORB pattern to one resembling WT and increased the Dip ratio. The degree of anatomical rescue in these mice was highly correlated with level of transgenic RS1 expression and with the restoration of ERG b-wave amplitudes. While the inner retinal cavity was significantly enlarged in dark-adapted Rs1KO mice, the Dip ratio was not altered. A reduction of the Dip ratio was also detected in AMD patients compared with healthy controls and was also positively correlated with AMD severity on the AMD score. We propose that the ORB and Dip ratio can be used as non-invasive early biomarkers for retina health, which can be used to probe therapeutic gene expression and to evaluate the effectiveness of therapy.

Background Epigallocatechin-gallate (EGCG) is a powerful antioxidant with suggested neuroprotective action. The aim of this study was to evaluate the effect of short-term supplementation of EGCG on inner retinal function in ocular hypertension (OHT) and open-angle glaucoma (OAG). Methods Eighteen OHT and 18 OAG patients (perimetric mean deviation: >−10 dB) were randomly assigned to assume oral placebo or EGCG over a 3-month period in a randomized, placebo-controlled, double-blind, cross-over design clinical trial (clinicaltrials.gov identifier: NCT00476138). Pattern-evoked electroretinograms (PERGs) to 1.6 cycles/degree square-wave gratings, counterphased at 16 reversals/second, and standard automated perimetry (Humphrey 30–2) were assessed at the study entry (baseline), and after 3 months of placebo or EGCG. Results After EGCG, PERGs of OAG, but not OHT patients were increased in amplitude, compared either to baseline values (mean amplitude change: 0.06 log μV, p  < 0.05) or to PERG amplitude values found in the same patients after placebo administration (mean change: −0.02 log μV, p not significant; difference between EGCG and placebo: 0.08 log μV, p  < 0.05). In both OHT and OAG patients, standard automated perimetry did not show significant changes after either EGCG or placebo. In individual OAG patients, the magnitude of PERG amplitude increment after EGCG was inversely related ( r  = −0.8, p  < 0.01) to corresponding baseline amplitudes. Conclusions Although this study cannot provide evidence for long-term benefit of EGCG supplementation in OAG, and the observed effect is small, the results suggest that EGCG might favourably influence inner retinal function in eyes with early to moderately advanced glaucomatous damage.

X-linked retinoschisis (XLRS) is a retinal disease caused by mutations in the gene encoding the protein retinoschisin (RS1) and is one of the most common causes of macular degeneration in young men. Our therapeutic approach for XLRS is based on the administration of AAV8-scRS/IRBPhRS, an adeno-associated viral vector coding the human RS1 protein, via the intravitreal (IVT) route. Two Good Laboratory Practice studies, a 9-month study in New Zealand White rabbits (n = 124) injected with AAV8-scRS/IRBPhRS at doses of 2E9, 2E10, 2E11, and 1.5E12 vector genomes/eye (vg/eye), and a 6-month study in Rs1-KO mice (n = 162) dosed with 2E9 and 2E10 vg/eye of the same vector were conducted to assess ocular and systemic safety. A self-resolving, dose-dependent vitreal inflammation was the main ocular finding, and except for a single rabbit dosed with 1.5E12 vg/eye, which showed a retinal detachment, no other ocular adverse event was reported. Systemic toxicity was not identified in either species. Biodistribution analysis in Rs1-KO mice detected spread of vector genome in extraocular tissues, but no evidence of organ or tissues damage was found. These studies indicate that IVT administration of AAV8-scRS/IRBPhRS is safe and well tolerated and support its advancement into a phase 1/2a clinical trial for XLRS.

Background Pattern electroretinogram (PERG) and optical coherence tomography (OCT) represent objective probes to investigate respectively the function of retinal ganglion cells and their structure as retinal nerve fiber layer (RNFL) thickness. We examined interindividual (II) correlations of PERG amplitude and RNFL thickness, as well as correlations between interocular (IO) differences in both measures, in ocular hypertension (OHT) and early glaucoma (EG) patients. Methods Thirty-one OHT, 34 EG (mean deviation: −1 to −6 dB) and 16 age-matched controls were examined in both eyes. Participants had clear optical media, no or moderate refractive errors and no concomitant ocular or systemic diseases. PERGs were elicited by counterphased (16.28 reversals/second) gratings (1.6 cycles/degree spatial frequency). The Fourier isolated 2nd harmonic PERG amplitude and phase were measured. RNFL thickness was quantified by means of OCT Stratus according to a standard protocol. Average, superior and inferior RNFL thicknesses were considered. Results Mean PERG amplitude was decreased ( p  < 0.01) in both OHT and EG patients compared to controls. Mean RNFL thicknesses were reduced ( p  < 0.01) in EG patients compared to both OHT and controls. In OHT patients, PERG amplitude did not correlate significantly with RNFL thickness in both II and IO analysis. In EG patients, PERG amplitude was positively correlated with RNFL thickness in both II ( p  < 0.005) and IO ( p  < 0.001) analysis. The slope of the correlation predicted that PERG losses exceeded systematically RNFL losses when the latter were between 0 and −0.25 log units. Conclusions Both II and IO analyses revealed a lack of structure–function relationship in OHT, suggesting that, at this disease stage, PERG losses appear to affect primarily retinal/optic nerve head function. In EG they reflect both dysfunction and RNFL loss.

Purpose To evaluate and compare the long-term outcomes of canaloplasty and phaco-canaloplasty in the treatment of open angle glaucoma and assess the prognostic factors associated with surgical outcome. Methods A 48-month retrospective analysis was performed on n  = 133 open angle glaucoma eyes treated with canaloplasty and n  = 57 open angle glaucoma eyes treated with phaco-canaloplasty by a single surgeon. Surgical success was defined according to six criteria, achieving a target intraocular pressure (IOP) ≤ 21, 18 or 15 mmHg on glaucoma medications (qualified success) or without any further treatment (complete success), including laser therapy or surgery. Kaplan–Meier survival analysis and Cox regression analysis were performed to evaluate surgical success and preoperative factors associated with surgical outcome. Surgical complications in the early postoperative period were compared between canaloplasty and phaco-canaloplasty. Results Canaloplasty and phaco-canaloplasty significantly reduced postoperative IOP and number of glaucoma medications ( p  = 0.001 for both). Phaco-canaloplasty showed higher rates of cumulative surgical success over canaloplasty, but only for target IOP ≤ 21 and ≤ 18 ( p  = 0.018 and p  = 0.011, respectively). A preoperative number of > 4 glaucoma medications predicted surgical failure. Phaco-canaloplasty was associated with a higher rate of IOP peaks in the first month compared with canaloplasty (40.4% vs 12.7%, p  = 0.000). Conclusion Canaloplasty and phaco-canaloplasty demonstrated long-term efficacy in the treatment of open angle glaucoma, with phaco-canaloplasty showing higher rates of surgical success compared to canaloplasty, but not for target IOPs lower than 16 mmHg. Patients on more than 4 preoperative glaucoma medications may not be good candidates for canaloplasty and may benefit from other surgical options.

Retinal oxidative damage, associated with an ATP-binding cassette, sub-family A, member 4, also known as ABCA4 gene mutation, has been implicated as a major underlying mechanism for Stargardt disease/fundus flavimaculatus (STG/FF). Recent findings indicate that saffron carotenoid constituents crocins and crocetin may counteract retinal oxidative damage, inflammation and protect retinal cells from apoptosis. This pilot study aimed to evaluate central retinal function following saffron supplementation in STG/FF patients carrying ABCA4 mutations. Methods: in a randomized, double-blind, placebo-controlled study (clinicaltrials.gov: NCT01278277), 31 patients with ABCA4-related STG/FF and a visual acuity >0.25 were randomly assigned to assume oral saffron (20 mg) or placebo over a six month period and then reverted to P or S for a further six month period. Full ophthalmic examinations, as well as central 18° focal electroretinogram (fERG) recordings, were performed at baseline and after six months of either saffron or placebo. The fERG fundamental harmonic component was isolated by Fourier analysis. Main outcome measures were fERG amplitude (in µV) and phase (in degrees). The secondary outcome measure was visual acuity. Results: supplement was well tolerated by all patients throughout follow-up. After saffron, fERG amplitude was unchanged; after placebo, amplitude tended to decrease from baseline (mean change: −0.18 log µV, p < 0.05). Reverting the treatments, amplitude did not change significantly. fERG phase and visual acuity were unchanged throughout follow-up. Conclusions: short-term saffron supplementation was well tolerated and had no detrimental effects on the electroretinographic responses of the central retina and visual acuity. The current findings warrant further long-term clinical trials to assess the efficacy of saffron supplementation in slowing down the progression of central retinal dysfunction in ABCA4-related STG/FF.