Retinal Area Research Articles

Multiwavelength photobiomodulation in atrophic age-related macular degeneration.

To evaluate photobiomodulation (PBM) safety and efficacy in patient with atrophic AMD and to explore tissue effects using Spectrally Resolved Autofluorescence (SrAF) to identify a potential biomarker indicative of mitochondrial activity, the primary PBM target. This retrospective, non-comparative case series involved six eyes of five patients with atrophic AMD, conducted at the Medical Retina and Imaging Unit, IRCCS San Raffaele Hospital in Milan, Italy. At baseline and follow-ups (after one and three months) a complete ophthalmological assessment and multimodal imaging, including spectrally resolved autofluorescence (SrAF), were performed. PBM treatment (Valeda Light Delivery System - LumiThera) was administered in nine sessions over three weeks. The SrAF images were analyzed to evaluate the effect of the treatment. Six eyes of five patients with atrophic AMD received PBM at baseline. Best corrected visual acuity (BCVA), mean central macular thickness (CMT), mean retinal sensitivity on microperimetry and the atrophic area have remained stable. No eyes developed foveal atrophy after the treatment. The image analysis in SrAF showed an increase in the highlighted area of 4.89% after one month and 17.11% after three months. No adverse systemic or local side effects were reported. PBM is a safe treatment for the human retina. The evaluation of the retinal area within the green light spectrum (575 nm) in SrAF is a potential indirect biomarker of mitochondrial activity and could be used to assess treatment efficacy in clinical studies.

Clinical and genetic characteristics of simple central serous chorioretinopathy according to age

ABSTRACT Purpose To investigate whether genetic and clinical characteristics differ depending on generations using 326 patients (male/female, 259/67; mean age, 55.4 ± 12.5 years) with simple CSC. Methods All patients were diagnosed with simple CSC, defined as a retinal pigment epithelium alteration area equal to or smaller than 2-disc areas based on multimodal imaging at the initial presentation. We cross-sectionally evaluated clinical characteristics at the initial visit and genotyped CFH rs800292 and rs1329428 for all patients using TaqMan technology. Results As generations decreased, the proportion of males, subfoveal choroidal thickness, and prevalence of fibrin significantly increased (p < 0.001, p < 0.001, and p = 0.012, respectively), and the best-corrected visual acuity improved (p < 0.001); in contrast, the prevalence of pachydrusen significantly decreased (p < 0.001). The younger presentation was significantly associated with male and risk variants (T allele) of CFH rs1329428 (p = 9.1 × 10−7 and p = 0.042, respectively), and patients were estimated to present 2 years younger per one T allele of CFH rs1329428 (p = 0.042, β = −1.95, stepwise regression analysis). Conclusion Clinical and genetic characteristics differed significantly among patients with simple CSC, depending on their generation.

Impairment of Neurovascular Function in Intermediate Age-Related Macular Degeneration.

To investigate neurovascular function in eyes with age-related macular degeneration (AMD). Subjects with bilateral large drusen (intermediate AMD) and healthy controls ≥50years old were recruited. The vasculature within the central 6 × 6-mm retinal area was captured using optical coherence tomography angiography (OCTA) and segmented to return superficial plexus, deep plexus, choriocapillaris, and choroid. OCTA scans were acquired without flicker light stimulation (conventional OCTA) and during flicker light stimulation to increase retinal activity and metabolic demand (functional OCTA). Vascular area density (VAD) and the vascular reactivity index (VRI; change in VAD induced by flicker stimulation) were determined and compared between control and AMD eyes. Thirty-five subjects (19 AMD cases and 16 healthy controls) participated in the study. In healthy eyes, flicker stimulation induced an increase in VAD (positive VRI, vasodilation) in the superficial plexus (P < 0.001) and deep plexus (P < 0.001). There was a trend for increased VAD in the choriocapillaris (P = 0.077), but there was no change in the choroid (P = 0.654). In AMD eyes, there was no change in VAD in response to flicker stimulation in any of the vascular layers examined (P ≥ 0.294). Linear mixed models confirmed that AMD was associated with a reduced VRI in the superficial plexus (P < 0.001) and deep plexus (P < 0.001). Eyes with large drusen show a reduction in retinal vascular reactivity compared to healthy eyes, which suggests that there is impairment of retinal neurovascular function in intermediate AMD. Functional OCTA could be used to study neurovascular function in retinal diseases.

Encoding of global visual motion in the avian pretectum shifts from a bias for temporal-to-nasal selectivity to omnidirectional excitation across speeds.

The pretectum of vertebrates contains neurons responsive to global visual motion. These signals are sent to the cerebellum, forming a subcortical pathway for processing optic flow. Global motion neurons exhibit selectivity for both direction and speed, but this is usually assessed by first determining direction preference at intermediate velocity (16-32 deg/sec), and then assessing speed tuning at the preferred direction. A consequence of this approach is that it is unknown if and how direction preference changes with speed. We measured directional selectivity in 114 pretectal neurons from 44 zebra finches (Taeniopygia guttata) across spatial and temporal frequencies, corresponding to a speed range of 0.062 to 1024°/s. Pretectal neurons were most responsive at 32-64°/s with lower activity as speed increased or decreased. At each speed, we determined if cells were directionally-selective, bidirectionally-selective, omnidirectionally responsive, or unmodulated. Notably, at 32°/s, 60% of the cells were directionally selective and 28% were omnidirectionally responsive. In contrast, at 1024°/s, 20% of the cells were directionally selective and nearly half of the population was omnidirectionally responsive. Only 15% of the cells were omnidirectionally excited across most speeds. The remaining 85% of the cells had direction tuning that changed with speed. Collectively, these results indicate a shift from a bias for directional tuning at intermediate speeds of global visual motion to a bias for omnidirectional responses at faster speeds. These results suggest a potential role for the pretectum during flight by detecting unexpected drift or potentials collisions, depending on the speed of the optic flow signal.Significance Statement During locomotion, images of edges and surfaces in the environment move across the retina, a signal of global visual motion called optic flow. Retinal recipient areas in the accessory optic system and the pretectum are the earliest sites to encode this signal, and the neurons are selective for direction and speed. Previous work suggested that directional selectivity may change across speeds but this has never been systematically studied. We measured direction preferences from 0.062 to 1024°/s in the avian pretectum. We found that pretectal global motion neurons are biased for temporal-to-nasal motion at intermediate speeds but biased for omnidirectional responses at faster speeds. These results suggest the pretectum could function to detect both unexpected drift and potential collisions during locomotion.

Retinal "sweet spot" for myopia treatment.

We studied which retinal area controls short-term axial eye shortening when human subjects were exposed to + 3.0D monocular defocus. A custom-built infrared eye tracker recorded the point of fixation while subjects watched a movie at a 2m distance. The eye tracker software accessed each individual movie frame in real-time and covered the points of fixation in the movie with a uniform grey patch. Four patches were programmed: (1) foveal patch (0-3 degrees), (2) annular patch (3-9deg), (3) foveal patch (0-3deg) combined with an annular patch (6-9deg), and (4) full-field patch where only 6-10deg were exposed to the defocus. Axial eye shortening was elicited similarly with full-field positive defocus and with the foveal patch, indicating that the fovea made only a minor contribution (-11 ± 12μm vs. -14 ± 17μm, respectively, n.s.). In contrast, patching a 3-9 degrees annular area or fovea together with an annular area of 6-9 degrees, completely suppressed the effect when compared with full-field defocus (+ 3 ± 1μm or -2 ± 13μm vs. -11 ± 12μm, respectively, p < 0.001). Finally, we found that the near-peripheral retina (6-10 degrees) is a "sweet spot" for positive defocus detection and alone can regulate eye growth control mechanism, and perhaps long-term refractive development (-9 ± 8μm vs. full-field: -11 ± 12μm, n.s.).

Nonlinear pathological trajectory of a high-myopia C57/BL6J mouse model induced by form deprivation.

To establish a high myopia model in C57BL/6J mice with monocular form deprivation myopia (FDM) and investigate its ocular structure pathological trajectory. Healthy 3-week-old C57BL/6J mice were divided into an FDM group (n = 36) and a control group (n = 24). The left eyes of the FDM group were patched, while the right eyes served as controls. Biometric parameters and fundus morphology were assessed at baseline and after 4, 8, and 12 weeks of form deprivation. Significant differences were observed in the deprived eyes, including longer axial length, higher refractive power, deeper vitreous chambers, thinner retina, choroid, and sclera, and smaller scleral fibers' diameters under a transmission electron microscope. Retinal vascular area proportion in covered eyes decreased significantly (P < 0.05), with a decline rate of 11% from weeks 4 to 8 and a faster decline of 19% from weeks 8 to 12, while this proportion increased significantly in control eyes. This study successfully induced a high myopia model in mice with long-term form deprivation. The axial length grew dramatically in FDM in the first 8 weeks, while the pathological progress of the fundus accelerated from weeks 8 to 12.

Sub-cone visual resolution by active, adaptive sampling in the human foveola.

The foveated architecture of the human retina and the eye's mobility enables prime spatial vision, yet the interplay between photoreceptor cell topography and the constant motion of the eye during fixation remains unexplored. With in vivo foveal cone-resolved imaging and simultaneous microscopic photo stimulation, we examined visual acuity in both eyes of 16 participants while precisely recording the stimulus path on the retina. We find that resolution thresholds were correlated with the individual retina's sampling capacity, and exceeded what static sampling limits would predict by 18%, on average. The length and direction of fixational drift motion, previously thought to be primarily random, played a key role in achieving this sub-cone diameter resolution. The oculomotor system finely adjusts drift behavior towards retinal areas with higher cone densities within only a few hundred milliseconds to enhance retinal sampling.

Sub-cone visual resolution by active, adaptive sampling in the human foveola

The foveated architecture of the human retina and the eye’s mobility enables prime spatial vision, yet the interplay between photoreceptor cell topography and the constant motion of the eye during fixation remains unexplored. With in vivo foveal cone-resolved imaging and simultaneous microscopic photo stimulation, we examined visual acuity in both eyes of 16 participants while precisely recording the stimulus path on the retina. We find that resolution thresholds were correlated with the individual retina’s sampling capacity, and exceeded what static sampling limits would predict by 18%, on average. The length and direction of fixational drift motion, previously thought to be primarily random, played a key role in achieving this sub-cone diameter resolution. The oculomotor system finely adjusts drift behavior towards retinal areas with higher cone densities within only a few hundred milliseconds to enhance retinal sampling.

Ultra-wide-angle peripheral refraction using a laser-scanning instrument

We compared the peripheral refractive measurements of a recently proposed laser-scanning instrument with an established peripheral refractor. Two-dimensional refractive maps were obtained using both instruments for 18 young subjects with differing values of central refraction. The comparison shows a strong correlation between devices in the overlapping measurement area, with the new device extending the range of the explored retinal area to a 100-degree-diameter circular patch, compared to the 60°x35° rectangular area of the older peripheral refractor. Larger refractive maps exhibit trends that cannot be easily predicted from narrower scans. These results demonstrate that the new instrument can be a useful tool for assessing wide-angle peripheral optical data in the human eye.

Diabetic Retinopathy Image Lesion Segmentation with Feature Fusion Relation Transformer Network

Diabetes is a common disease that affects different vital organs of the human body, including the eyes. In diabetic patients, a change in blood sugar level leads to eye problems. Around 80% of the patients who have diabetes for more than 10 years have severe eye-related pathological disorders such as retinopathy and maculopathy. Proper detection, diagnosis, and treatment of eye-related pathologies prevent damage to the eye during the earliest stages of diabetic disease—the developed stage findings in patients losing their vision. The retinal damage due to diabetes is termed Diabetic Retinopathy (DR). The treatment of DR involves detecting the presence of the disease in the form of microaneurysms (MA), hemorrhages (HE), and exudates (EX) in the retinal area. The process of segmenting a massive segment of Retinal Images (RI) performs a prominent role in DR classification. The existing research concentrates on Optic Disc (OD) segmentation. This article focuses on the segmentation of MA, HE, and EX using a Feature Fusion Relation Transformer Network (FFRTNet). In this research, the benchmark dataset, the Indian Diabetic Retinopathy Image Dataset (IDRID), is used for the ablation study to evaluate the use of every module. The proposed method, FFRTNet, is compared with state-of-the-art methods. The evaluation of FFRTNet enhances the segmentation by 3.56%, 4.34%, and 3.75% on metrics, namely sensitivity, Intersection-over-Union (IoU), and Dice coefficient (DICE). The qualitative and quantitative results proved the superiority of FFRTNet in segmenting lesions in DR.

A NOVEL USE OF FINESSE FLEX LOOP FOR PROLIFERATIVE VITREORETINOPATHY (FINESSE LOOP- ASSISTED PHOTOCOAGULATION)

Purpose: To describe a novel use of the flexible nitinol loop membrane scraper (Finesse Flex Loop; Alcon, Forth Worth, TX) for applying an effective endolaser photocoagulation in proliferative vitreoretinopathy (PVR) cases. Methods: A 27- gauge nitinol flex loop was used to assist applying endolaser photocoagulation to enhance its effectiveness in a case with PVR. Results: A 66-year-old female was presented with PVR after an unsuccessful pars plana vitrectomy and silicone oil injection for rhegmatogenous retinal detachment in her right eye. The patient underwent 25- gauge pars plana vitrectomy, preretinal membrane removal, inferior retinectomy, the nitinol flex loop assisted endolaser photocoagulation, and silicone oil reinjection. After the silicone oil extraction, the retina was reattached and her visual acuity had improved from 0.1 (20/200) to 0.3 (20/60). Conclusion: The nitinol flex loop can be used to assist endolaser photocoagulation and enhance its effectiveness in PVR cases and reduce the retinal excision area which results unnecessary large retinal defects that may lead to redetachment of the retina.

Widefield Retinal Imaging in Gyrate Atrophy: Correlation of Structural, Biochemical, and Functional Characteristics

ObjectivesTo profile a cohort of gyrate atrophy patients classified by widefield retinal imaging and correlate the structural, biochemical, and functional characteristics. DesignRetrospective observational cohort study. ParticipantsSixty-five patients (129 eyes) with gyrate atrophy. MethodsData of participants with a diagnosis of gyrate atrophy were retrieved from their electronic medical records (January 2015 to December 2023). Retinal involvement was classified into three zones using widefield retinal images. Zone 3 had atrophic patches in the area anterior to the equator; Zone 2 had involvement limited to the arcades but posterior to the equator; Zone 1 had involvement within the vascular arcades and/or peripapillary region, with or without any other zone involvement. Macular assessment was performed using swept-source OCT (n=104). Flash ERG was performed in 40 eyes. serum ornithine levels (n=35) were measured, and genetic analysis was conducted (n=18). Main Outcome MeasuresDemography, patient profile, zone of retina involved, macular features, and serum ornithine levels. ResultsThe average age at presentation was 26.4 (range: 5-67) years, majority were male. Nyctalopia (n=35, 53.8%) and blurred vision (n=29, 44.6%) were the most common symptoms. Positive family history was reported in 32.3% of patients. Most eyes were myopic (69.8%<-3 D). Posterior subcapsular cataracts were documented in 36.4% of eyes. The highest frequency of retinal area affected was Zone 1 (57.14%), followed by Zone 2 (33.33%) and Zone 3 (9.52%), correlating with age at presentation. Foveoschisis was observed in 57.7% of eyes, with a higher prevalence in eyes with Zone 1 disease. Elevated serum ornithine levels (>163 μmol/L) were found in 77.14% of patients. ERG showed non-recordable (n=32) or severely reduced (n=8) responses in scotopic and photopic phases. Genetic analysis of 18 patients identified mutations in the OAT gene, including a novel missense variant (c.290T>C). ConclusionsThis large cohort of patients with gyrate atrophy revealed symmetrical involvement, predominantly in Zone 1. Most patients presented between the first and third decades, experienced nyctalopia, vision reduction, early posterior subcapsular cataracts, and varying degrees of myopia. Zone 1 involvement was strongly associated with foveoschisis and visual compromise.

Peripheral Superficial Retina Vascular Density and Area of Radial Peripapillary Capillaries Changes in Myopic Individuals: A Wide-Field OCT Angiography Study.

Using swept-source optical coherence tomography (SS-OCT) to explore the effect of high myopia on superficial retina vascular density (SVD) of the peripheral region and the area of radial peripapillary capillaries (RPCs). In this cross-sectional study, a total of 91 volunteers (34 male subjects and 57 female subjects) were recruited and 34 individuals in the high myopic group (group A) and 57 individuals in the low myopic group (group B). Using the wide-field OCT-angiography (OCTA; 24 × 20 mm, 120 degrees angular field) compared the peripheral SVD and the area of RPC between the two groups and investigated its correlation with ocular axial length and diopter. Peripheral SVD of group B around the supratemporal (SVD1), supranasal (SVD2), infratemporal (SVD3), and infranasal (SVD4) directions were significantly higher than those of group A (all P < 0.05). The RPC area of group B around the supranasal (RPC2) and infranasal (RPC4) were significantly larger than that of group A (all P < 0.01). Ocular axial length and diopter were significantly correlated with SVD2 and SVD4 (all P < 0.05), and they also have a significant correlation with the supratemporal (RPC1), RPC2, and RPC4 (all P < 0.05). Peripheral SVD was decreased and the RPC area was mainly reduced on the nasal side in the high myopic group. Peripheral SVD and area of RPC are significantly correlated with ocular axial length and diopter. The wide-field OCTA can be used for new detection of myopia's impact on the retinal peripheral SVD and area of peripapillary RPC, offering new insights into the progression of myopia.

Variability in oil droplet numbers and proportions in the retinas of anole lizards

Colored oil droplets are a common feature in the cones of almost all diurnal lizards. Using white light microscopy, three chromotypes of droplet can be identified in anoles – yellow, green and colorless. These droplets have been associated with different cone classes using microspectrophotometry. The principal member of double cones contain a yellow droplet while the accessory member contains a diffuse yellow pigment. Both members contain the LWS visual pigment. One class of large single cone contains a yellow droplet and the LWS visual pigment. The two remaining classes of large single cone contain the green droplet and either the LWS or MWS visual pigment. As such, by noting the distribution and numbers of the different droplet chromotypes, information about cone distribution, type, and number can be deduced microscopically. Retinas from three anole species (A. cristatellus, A. sagrei, and A. carolinensis) were isolated, flattened and oriented using the two foveae as landmarks. A 19-gauge needle was used to punch out six full-thickness retinal disks from identical retinal regions from both eyes of the three species. The different oil droplets were microscopically identified by color and counted. In all three species at all six retinal areas, the colorless droplets associated with the UVS and SWS single cones represented approximately 10% of the total droplets counted. However, the proportions of the yellow and green droplets were significantly different between the species. For A. cristatellus, 80% of the droplets were green while 10% were yellow. For A. sagrei approximately 85% of the droplets were yellow while only 5% were green. For A. carolinensis 50% of the droplets were yellow while 40% were green. The possible significance of these variable proportions is discussed in terms of possible effects on color vision and ecotype of the three anoles.

Framework Nucleic Acids Loaded with Quercetin: Protecting Retinal Neurovascular Unit via the Protein Kinase B/Heme Oxygenase-1 Pathway.

Retinal neovascular disease is a leading cause of vision loss and blindness globally. It occurs when abnormal new blood vessels form in the retina. In this study, we utilized tetrahedral framework nucleic acids (tFNAs) as vehicles to load quercetin (QUE), a small-molecule flavonoid, forming a deoxyribonucleic acid (DNA) nanocomplex, tFNAs-QUE. Our data show this nanocomplex inhibits pathological neovascularization, reduces the area of retinal nonperfusion area, protects retinal neurons, and preserves the visual function. Further, we discovered that tFNAs-QUE selectively upregulates the AKT/Nrf2/HO-1 signaling pathway, which can suppress pathological vascular growth and exert antioxidative effects. Therefore, this study presents a promising small-molecule-loading mechanism for the treatment of ischemic retinal diseases.

Development and evaluation of a deep learning model for automatic segmentation of non-perfusion area in fundus fluorescein angiography

Diabetic retinopathy (DR) is the most prevalent cause of preventable vision loss worldwide, imposing a significant economic and medical burden on society today, of which early identification is the cornerstones of the management. The diagnosis and severity grading of DR rely on scales based on clinical visualized features, but lack detailed quantitative parameters. Retinal non-perfusion area (NPA) is a pathogenic characteristic of DR that symbolizes retinal hypoxia conditions, and was found to be intimately associated with disease progression, prognosis, and management. However, the practical value of NPA is constrained since it appears on fundus fluorescein angiography (FFA) as distributed, irregularly shaped, darker plaques that are challenging to measure manually. In this study, we propose a deep learning-based method, NPA-Net, for accurate and automatic segmentation of NPAs from FFA images acquired in clinical practice. NPA-Net uses the U-net structure as the basic backbone, which has an encoder-decoder model structure. To enhance the recognition performance of the model for NPA, we adaptively incorporate multi-scale features and contextual information in feature learning and design three modules: Adaptive Encoder Feature Fusion (AEFF) module, Multilayer Deep Supervised Loss, and Atrous Spatial Pyramid Pooling (ASPP) module, which enhance the recognition ability of the model for NPAs of different sizes from different perspectives. We conducted extensive experiments on a clinical dataset with 163 eyes with NPAs manually annotated by ophthalmologists, and NPA-Net achieved better segmentation performance compared to other existing methods with an area under the receiver operating characteristic curve (AUC) of 0.9752, accuracy of 0.9431, sensitivity of 0.8794, specificity of 0.9459, IOU of 0.3876 and Dice of 0.5686. This new automatic segmentation model is useful for identifying NPA in clinical practice, generating quantitative parameters that can be useful for further research as well as guiding DR detection, grading severity, treatment planning, and prognosis.

The effect of long-term hemodialysis on diabetic retinopathy observed by swept-source optical coherence tomography angiography

BackgroundDiabetes can cause chronic microvascular complications such as diabetic retinopathy (DR) and diabetic nephropathy (DN). DR and DN can lead to or exacerbate diabetic macular edema (DME). Hemodialysis (HD) is the main treatment method for patients with end-stage kidney disease (ESKD) secondary to DN.PurposeThe aim of this prospective cohort study was to determine the immediate effect of single HD session on retinal and choroidal thickness in DR patients with ESKD and the features of DR and the prevalence of DME in these patients who have received long-term HD.MethodsEighty-five eyes of 44 DR patients with ESKD who underwent long-term HD were examined by swept-source optical coherence tomography angiography (SS-OCTA). Based on OCTA images, the characteristics of DR and the prevalence of DME in these patients were analyzed. Changes in central retinal thickness (CRT), central retinal volume (CRV), subfoveal choroidal thickness (SFCT) and subfoveal choroidal volume (SFCV) within 30 min before and after single HD session were compared. CRT, CRV, SFCT and SFCV were compared before single HD session and before the next single HD session.ResultsThere was no significant difference in the average CRT (251.69 ± 39.21 μm vs. 251.46 ± 39.38 μm, P = 0.286) or CRV (0.15 ± 0.62 μm vs. 0.15 ± 0.63 μm, P = 0.324) between before and after single HD session. After single HD session, SFCT (243.11 ± 77.15 μm vs. 219.20 ± 72.84 μm, P < 0.001) and SFCV (0.15 ± 0.10 μm vs. 0.13 ± 0.90 μm, P < 0.001) significantly decreased. There was no statistically significant difference in CRT (251.69 ± 39.21 μm vs. 251.11 ± 38.47 μm, P = 0.206), CRV (0.15 ± 0.62 μm vs. 0.15 ± 0.61 μm, P = 0.154), SFCT (243.11 ± 77.15 μm vs. 245.41 ± 76.23 μm, P = 0.108), or SFCV (0.15 ± 0.10 μm vs. 0.16 ± 0.10 μm, P = 0.174) before HD and before the next single HD session. On en face OCTA images, eighty-five eyes (100%) had retinal nonperfusion areas, foveal avascular zone (FAZ) enlargement, and abnormal retinal microvasculature. Based on cross-sectional OCTA images, retinal neovascularization (RNV) was confirmed in 42 eyes (49.41%), and intraretinal microvascular abnormalities (IRMAs) were detected in 85 eyes (100%). Seventeen eyes (20%) still had DME, all of which were cystoid macular edema (CME). Among eyes with DME, the epiretinal membrane (ERM) was present in 7 eyes (8.24%).ConclusionsFor DR patients with ESKD who have undergone long-term HD, the choroidal thickness still changes significantly before and after single HD session, which may be related to short-term effects such as reduced blood volume and plasma osmotic pressure caused by single HD session. Although macular features seem to have stabilized in DR patients undergoing long-term dialysis, the DR of patients with ESKD should still be given attention.

Lipid-based nanocarriers mediated Axitinib retinal delivery after topical instillation: Formulations setting up and in vivo evidence

Axitinib (AXB) is a multi-receptor tyrosine kinase inhibitor molecule. It acts by blocking the receptors for vascular endothelial growth factor (VEGFR) and platelet-derived growth factor (PDGFR), which are responsible for the development of neovascularization. To date, intravitreal injections of anti-VEGF have become the first-line medical treatment for diabetic macular oedema, a degeneration of diabetic retinopathy. Despite the efficacy of intravitreal injections, the complications of this type of administration are manifold. Our study aimed to design a nanotechnological formulation capable of delivering AXB to the retinal area after topical administration. Two different lipid-based formulations, namely solid lipid nanoparticles (SLN) and nanostructured lipid nanocarriers (NLC) were developed through a design of experiment (DoE) approach. The formulations possessed a mean particle size below 200 nm, low PDI values and a high drug encapsulation efficiency, thus designating them as suitable for ocular administration. Stability studies were performed at different storage conditions according to ICH guidelines. Strategies to improve AXB concentration in the retinal target were finally developed, such as using cationic lipids and increasing AXB loading in the nanocarriers. The in vivo PK studies indicated that cationic NLC loaded with AXB at 4 mM were the most efficient in delivering the drug to the retina, proposing them as a potential topical treatment for DR.

Assessment of Baseline Ultrawidefield Fluorescein Angiographic Quantitative Leakage Parameters with Ultrawidefield Fundus Features and Clinical Parameters in Diabetic Retinopathy in Protocol AA

PurposeEvaluate quantitative leakage parameters on ultra-widefield fluorescein angiography (UWF-FA) images and explore their association with Diabetic Retinopathy Severity Scale (DRSS), predominantly peripheral lesions (PPLs), visual acuity, and clinical characteristics. DesignA post-hoc analysis of baseline UWF-FA images in the DRCR Retina Network observational study Protocol AA. ParticipantsN = 575 eyes from 384 adults across 38 sites in the US and Canada with gradable UWF-FA. MethodsA machine learning-enhanced feature extraction platform provided initial leakage segmentation of UWF-FA images sequentially reviewed and corrected by two certified readers for segmentation accuracy. UWF-FA leakage was measured in five retinal zones: panretinal (whole retina), central macular (3-disc diameter fovea-centered circle), posterior pole (6-disc diameter fovea-centered circle), peripheral (outside 6-disc diameter circle) and widefield far peripheral (outside 9-disc diameter circle); associations with clinical factors were evaluated with marginal beta regression models. Main Outcome MeasuresUWF-FA leakage index, calculated as the area with leakage divided by the analyzable retinal area. ResultsThe mean quantitative leakage index was 3.5% for panretinal, 6.6% for macular, 4.8% for posterior pole, 3.3% for peripheral and 2.8% for wide-field far peripheral retinal zones. Panretinal leakage was associated with DRSS (mean 2.2% for no to mild NPDR, 3.4% for moderate NPDR, 4.2% for moderately severe NPDR, 4.8% for severe NPDR and 5.1% for PDR; P<.001), HbA1c (3.2% for HbA1c <8% vs. 3.8% for HbA1c ≥8%; P=.01 for continuous HbA1c), visual acuity (3.3% for 20/25 or better vs. 4.7% for 20/32 or worse; continuous P<.001), and UWF-FA-PPL types of IRMA (4.3% vs. 3.3%; P=.005) or NVE (5.7% vs. 3.4%; P=.003). DRSS was also statistically significant for leakage within all retinal zones (P<.001); eyes with non-central DME versus no DME had higher mean leakage in the central macular (11.2% vs. 5.9%; P=0.005) and posterior pole regions (9.2% vs. 4.2%; P=.002). ConclusionQuantitative UWF-FA leakage analysis identified associations between leakage and DRSS, visual acuity, and presence of DME. In the future, quantitative UWF-FA leakage parameters may be explored as potential biomarkers for disease progression risk.

Optical Assessment of Photoreceptor Function Over the Macula.

The purpose of this study was to develop next-generation functional photoreceptor imaging using ultrahigh-speed swept-source optical coherence tomography (UHS-SS-OCT) and split-spectrum amplitude-decorrelation optoretinography (SSADOR) algorithm. The advancement enables rapid surveying of large retinal areas, promising non-contact, objective, and quantifiable measurements of macular visual function. We designed and built a UHS-SS-OCT prototype instrument using a wavelength tunable laser with 1 MHz A-scan rate. The functional scanning protocol records 5 repeated volumes in 3 seconds. A flash pattern selectively exposes the imaged retina area. SSADOR quantifies photoreceptor light response by extracting optical coherence tomography (OCT) signal changes within the photoreceptor outer segment before and after the flash. The study prospectively enrolled 16 eyes from 8 subjects, demonstrating the ability to measure photoreceptor light response over a record field of view (3 × 3mm2) with high topographical resolution (approximately 100 µm). The measured SSADOR signal corresponds to the flashed pattern, whose amplitude also correlates with flash strength, showing consistency and reproducibility across subjects. The integration of high-performance UHS-SS-OCT and SSADOR enables characterizing photoreceptor function over a clinically meaningful field of view, while maintaining a workflow that can be integrated into routine clinical tests and trials. The new approach allows detecting changes in photoreceptor light response with high sensitivity and can detect small focal impairments. This innovative advance can enable us to detect early photoreceptor abnormalities, as well as help to stage and monitor degenerative retinal diseases, potentially providing a surrogate visual function marker for retinal diseases and accelerating therapeutic development through a safe and efficient outcome endpoint.