Choroidal Changes During and After Discontinuing Long-Term 0.01% Atropine Treatment for Myopia Control.

Purpose: Few studies have explored choroidal changes after cessation of myopia control. This study evaluated the choroidal thickness (ChT) and choroidal vascularity index (CVI) during and after discontinuing long-term low-concentration atropine eye drops use for myopia control. Methods: Children with progressive myopia (6-16 years; n = 153) were randomized to receive 0.01% atropine eye drops or a placebo (2:1 ratio) instilled daily over 2 years, followed by a 1-year washout (no eye drop use). Optical coherence tomography imaging of the choroid was conducted at the baseline, 2-year (end of treatment phase), and 3-year (end of washout phase) visits. The main outcome measure was the subfoveal ChT. Secondary measures include the CVI. Results: During the treatment phase, the subfoveal choroids in both treatment and control groups thickened by 12-14 µm (group difference P = 0.56). During the washout phase, the subfoveal choroids in the placebo group continued to thicken by 6.6 µm (95% confidence interval [CI] = 1.7 to 11.6), but those in the atropine group did not change (estimate = -0.04 µm; 95% CI = -3.2 to 3.1). Participants with good axial eye growth control had greater choroidal thickening than the fast-progressors during the treatment phase regardless of the treatment group (P < 0.001), but choroidal thickening in the atropine group's fast-progressors was not sustained after stopping eye drops. CVI decreased in both groups during the treatment phase, but increased in the placebo group after treatment cessation. Conclusions: On average, compared to placebo, 0.01% atropine eye drop treatment did not cause a differential rate of change in ChT during treatment, but abrupt cessation of long-term 0.01% atropine eye drops may disrupt normal choroidal thickening in children.

Effects of Topic Delivery of an Inhibitor of Serine Racemase on Laser-Induced Choroidal Vasculopathy.

Purpose: Intravitreal injection of anti-VEGF antibodies remains the primary therapy for exudative age-related macular degeneration (exAMD), although its efficacy is limited. Previous research has demonstrated that both a loss-of-function mutation of srr and the intravenous injection of a serine racemase inhibitor, L-aspartic acid ß-hydroxamate (L-ABH), significantly inhibit laser-induced choroidal neovascularization (CNV) in mice. Given that L-ABH is a small molecule, this study investigated the effects of L-ABH administered via eye drops on CNV, aiming to develop a noninvasive treatment strategy for exAMD. Methods: CNV models in mice and rhesus macaques were established through laser photocoagulation. Seven monkeys were randomly assigned to receive either saline solution or L-ABH eye drops. Intraperitoneal or intravenous injection of fluorescein characterized CNV in both mice and monkeys. Fluorescein fundus angiography was used to assess leakage, whereas optical coherence tomography measured retinal thickness in the monkeys. Results: L-ABH eye drops significantly reduced fluorescein leakage in laser-injured mice (P < 0.001 compared to saline). In laser-injured rhesus macaques, the average percent changes in leakage areas treated with L-ABH were 2.5% ± 25.8% (P = 0.004) and 1.5% ± 75.7% (P = 0.023 compared to saline solution) on day 14 and day 28, respectively. However, L-ABH eye drops did not significantly affect the number of grade IV laser spots or retinal thickness, whereas bevacizumab did. Conclusions: This study demonstrates the potential efficacy of an SRR inhibitor in two animal models of laser-induced CNV. Translational Relevance: This represents the first investigation into the effects of topical delivery of an SRR inhibitor on CNV.

Topographic analysis of retinal and choroidal vascular displacements after macular hole surgery.

It has been reported that the retinal vessel and macular region of the retina are displaced after macular hole (MH) surgery. However, there is no detailed information for correlations between retinal and choroidal displacements. We obtained optical coherence tomography angiography (OCTA) and en-face optical coherence tomography (OCT) images from 24 eyes to measure the retinal and choroidal vascular displacement before and after surgery. These images were merged into infrared images using blood vessel patterns. The same vascular bifurcation points were automatically selected for each follow-up image, and the displacements of the bifurcation points were analyzed as a vector unit for prespecified grid regions in a semi-automated fashion. The results showed displacements of the choroidal intermediate vessels and retinal vessels following MH surgery (p = 0.002, p < 0.001). The topographic changes showed inferior, nasal, and centripetal displacement of the retina and inferiorly displaced choroid. The ILM peeling size and basal MH size were significantly associated with the retinal displacement (p < 0.001 and p = 0.010). Additionally, changes in the amount of the choroidal displacement were significantly correlated with that of the retinal displacements (p = 0.002). Clinicians should keep in mind that there might be topographic discrepancies of the displacement between retina and choroid when analyzing them following surgery.

In vivo multi-contrast depth-resolved choroidal imaging of a mouse using polarization-diversity optical coherence tomography.

The results of depth-resolved multi-contrast in vivo mouse choroidal imaging using a polarization-diversity optical coherence tomography (PD-OCT) system are presented. A selectively chosen depth of focus that was fine-tuned with a sensorless adaptive optics technique and a simple segmentation based on the degree of polarization uniformity signal visualizes the detailed features of a mouse choroid from the OCT angiography images. A comprehensive image analysis of the choroid revealed the distinctive pathological characteristics of the laser-induced choroidal neovascularization mouse.

Early and Late Treatment Influence on Chorioretinal Microvasculature in Vogt-Koyanagi-Harada Patients Using Optical Coherence Tomography Angiography.

Purpose: To study the impact of early and late treatment on chorioretinal microvasculature in Vogt-Koyanagi-Harada (VKH) disease using optical coherence tomography angiography (OCTA). Methods: A total of 103 patients with VKH disease were divided into early (group 1, starting treatment within 2 months after disease onset) and late (group 2, starting treatment 2 months after disease onset) treatment groups. Flow area (FA) and vessel density (VD) of the retinal superficial vascular complex (SVC) and deep vascular complex (DVC), FA of the choriocapillaris, three-dimensional choroidal vascular volume (CVV), and choroidal vascularity index (CVI) were analyzed and compared to 103 healthy individuals. The relationship between the final best-corrected visual acuity (BCVA) and the aforementioned parameters was also analyzed. Results: FA of the SVC (all P < 0.05, except 0-1 mm P = 0.087), DVC (all P < 0.05), choriocapillaris (1-2.5 mm P = 0.033), and CVV (all P < 0.05) were lower in group 2 as compared to group 1. Compared to healthy controls, FA of the SVC (all P < 0.001, except 0-1 mm P = 0.104) and DVC (all P < 0.05), VD of the SVC (1-2.5 mm P = 0.001) and DVC (1-5 mm P = 0.003, 2.5-5 mm P < 0.001), FA of the choriocapillaris (all P < 0.05), and CVV (total area P = 0.049, 1-5 mm P = 0.045, 2.5-5 mm P = 0.041) were lower in group 2, while FA (all P < 0.05, except 0-1 mm P = 0.925) and VD (1-5 mm P = 0.003, 2.5-5 mm P = 0.004) of the DVC and FA of the choriocapillaris (total area P = 0.007, 0-1 mm P < 0.001, 1-2.5 mm P = 0.007) were lower in group 1. There was no significant difference concerning CVI among groups (all P > 0.05). FA of the SVC, DVC, and choriocapillaris and VD of DVC and CVI were negatively associated with the final logarithm of the minimum angle of resolution BCVA. Conclusions: Patients with VKH disease who are treated within 2 months of disease onset showed a better chorioretinal microvascular outcome as defined by OCTA compared to those treated late. Translational Relevance: Our study employs OCTA to design three-dimensional metrics for the retina and choroid, bridging the gap between traditional two-dimensional OCTA findings and enhanced clinical outcomes for patients with VKH disease.

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

BACKGROUND: Diabetes 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. PURPOSE: The 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. METHODS: Eighty-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. RESULTS: There 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%). CONCLUSIONS: For 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.

Choroidal Vascularity and Axial Length Elongation in Highly Myopic Children: A 2-Year Longitudinal Investigation.

Purpose: To examine the influence of subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI) on axial length (AL) elongation over a 2-year period in highly myopic children. Methods: In this is prospective, longitudinal, observational study, 163 participants (74%), who were 8 to 18 years of age with bilateral high myopia (sphere ≤ -6.0 D) and without pathologic myopia, completed follow-up visits over 2 years. All participants underwent baseline and follow-up ocular examinations, including swept-source optical coherence tomography (SS-OCT) and AL measurements. SFCT and CVI were derived from SS-OCT scans using a deep-learning-based program for choroidal structure assessment. Results: The mean age of the participants at baseline was 15.0 years (±2.3), with males constituting 47% of the cohort. An inverse relationship was observed between AL elongation and increases in baseline age, baseline SFCT, and CVI, as well as a decrease in baseline AL. Adjusting for other factors, every 10-µm increase in SFCT and each 1% increase in CVI were associated with decreases in AL elongation of 0.007 mm (95% confidence interval [CI], -0.013 to -0.002; P = 0.011) and 0.010 mm (95% CI, -0.019 to 0.000; P = 0.050), respectively. The incorporation of SFCT or CVI into predictive models improved discrimination over models using only age, gender, and baseline AL (both P < 0.05, likelihood ratio test). Conclusions: Our findings suggest a possible association between a thinner choroid and increased AL elongation over 2 years in children with high myopia, after adjusting for potential baseline risk factors such as age, gender, and initial AL.

Association of choroidal thickness and blood flow features with asymmetric axial lengths in children with unilateral myopic anisometropia.

BACKGROUND: Considering that changes in the choroidal thickness are closely related to ocular growth, we studied the choroidal thickness (CT) and the blood flow features in children with unilateral myopic anisometropia (UMA) as well as investigating the relationship between choroidal changes and myopia. METHODS: Subjective refractive, axial length (AL), and biometric parameters were measured in 98 UMA children (age: 8-15 years). CT and choroidal blood-flow features, including the choroidal vessel volume (CVV), choroidal vascularity index (CVI), and choriocapillaris perfusion area (CCPA), were measured through swept-source optical coherence tomography angiography. The macular region was categorized into four concentric circles of diameters 0-1 mm (central fovea), 1-3 mm (parafovea), 3-6 mm (perifovea), and 6-9 mm (extended), and further categorized into superior (S), inferior (I), temporal (T), and nasal (N) quadrants. RESULTS: The aforementioned four regions of myopic eyes displayed significantly lower CT, CVV, and CVI than those of non-myopic eyes. CCPA changes differed across different regions of both the eyes (parts of N and T quadrants). There was an inverse association between CT and the interocular AL difference (central and other regions S, T quadrant). No correlation was noted between CVV and CVI with interocular AL difference. CT and CVV were positively correlated in the 0-6-mm macular region of myopic eyes (Spearman correlation coefficient = 0.763, P < 0.001). CONCLUSIONS: In UMA children, CCT and blood flow may be related to myopia progression. A robust correlation between CT and CVV in the 0-6-mm macular region and reduced CT and diminished blood flow indicated an association with myopia.

Influence of Carotid Artery Stenting on the Retina and Choroid.

Purpose: The effect of carotid artery stenting in patients with unilateral carotid artery stenosis on the retina and choroid was evaluated using swept-source optical coherence tomography angiography (SS-OCTA). Methods: SS-OCTA examination was conducted before stenting and 4 days and 3 months after stenting. The retinal nerve fiber layer, ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer, superficial vascular complex (SVC), deep vascular complex (DVC), choroidal vascular volume (CVV), and choroidal vascular index were measured. Repeated-measures analysis of variance was performed to assess the impact of carotid artery stenting on optical coherence tomography angiography (OCTA) metrics. Results: At baseline, 303 eyes from 160 patients (61.82 ± 9.98 years; 85.29% males) were enrolled. SVC and DVC densities and CVV were lower in ipsilateral eyes (stenosed side) compared to contralateral eyes (all P < 0.05). Four days after stenting, a significant increase was seen in SVC density in ipsilateral eyes (P < 0.05) while a significant increase was seen in CVV in ipsilateral eyes and contralateral eyes (both P < 0.05). Three months after stenting (63 patients with 114 eyes), a significant decrease was seen in the GCIPL thickness of ipsilateral and contralateral eyes (all P < 0.001). Conclusions: Short term after carotid artery stenting, ipsilateral eyes showed a rapid and significant increase in SVC density and CVV. Translational Relevance: Optical coherence tomography (OCT)/OCTA measurements may have the potential to detect retinal and choroidal changes after stenting. Future research on the long-term effect of stenting on the retina and choroid will be guided by these findings.

Choroidal and retinal exudative changes following extensive endolaser pan retinal photocoagulation.

BACKGROUND: In this report, we describe a case of proliferative diabetic retinopathy that developed into exudative changes confusing with central serous chorioretinopathy (CSCR) following extensive endolaser pan retinal photocoagulation. CASE DESCRIPTION: A 49-year-old male patient with diabetic retinopathy in both eyes presented with vitreous hemorrhage and 6/60 visual acuity in his left eye. Optical coherence tomography (OCT) scans at presentation revealed serous PEDs in both eyes. On day 10 after vitreoretinal surgery and complete peripheral endolaser PRP for the left eye, there was serous retinal detachment (SRD) and an increase in PED heights, mimicking CSCR. No additional treatment was considered. At the three-week post-operative visit, OCT scans revealed that the SRD had resolved and the PED heights had decreased without rupture. At the final follow-up visit, 12 weeks after surgery, the SRD had not recurred, and the PEDs had stabilized. Despite no additional ocular therapy for the right eye, the serous PED height had decreased. The choroidal thickness (CT) at the fovea at various points during the follow-up visits revealed a reduction in both eyes. CONCLUSION: This case demonstrated the course of SRD, PED, and CT following extensive PRP. These changes may be associated with intraocular VEGF changes. In the presence of SRD and serous PED, the PED morphology may help differentiate the condition from CSCR. Although caution should be exercised when performing PRP during surgery or as an outpatient procedure, the SRD usually resolves without problem.

Retinal and choroidal microvascular features during pregnancy: a systematic review and meta-analysis.

PURPOSE: To analyse retinal and choroidal microvasculature features in healthy pregnant women using optical coherence tomography angiography (OCTA). METHODS: PubMed, Embase, Ovid, Web of Science and Cochrane Library were searched for published studies that compare retinal and choroidal microvasculature characteristics between pregnant females and non-pregnant females from inception to November 2023. The statistics were continuous variables. They were presented as the mean difference (MD) with a corresponding 95% CI. We used Review Manager software 5.4.1 for statistical analysis. RESULTS: A total of 5 eligible studies involving 219 eyes in the pregnancy group and 186 eyes in the control group were included in the meta-analysis. The pooled results showed that the retinal deep capillary plexus vascular density (DCP VD) measured by OCTA was significantly higher in healthy pregnant women than in controls (MD 1.53; 95% CI 0.62 to 2.44; I2=0%; p=0.0009). However, differences between the two groups in the retinal superficial capillary plexus VD (SCP VD) (MD 0.41;95% CI -1.26 to 2.09; I2=85%; p=0.63), the foveal avascular zone (FAZ) (MD 0.01; 95% CI -0.01 to 0.03; I2=14%; p=0.18), the choriocapillaris VD (CC VD) (MD 0.76; 95% CI -1.11 to 2.64; I2=79%; p=0.43) were uncertain. CONCLUSIONS: Our meta-analysis found that the DCP VD of healthy pregnant women was higher than that of non-pregnant controls. However, differences in SCP VD, FAZ and CC VD between the healthy pregnant women and the non-pregnancy controls were uncertain. Our findings can help to get a deeper understanding of retinal and choroidal microvascular characteristics during pregnancy.

Association of outer retinal and choroidal alterations with neuroimaging and clinical features in posterior cortical atrophy.

BACKGROUND: Posterior cortical atrophy (PCA) is a rare condition characterized by early-onset and progressive visual impairment. Individuals with PCA have relatively early-onset and progressive dementia, posing certain needs for early detection. Hence, this study aimed to investigate the association of alterations in outer retinal and choroidal structure and microvasculature with PCA neuroimaging and clinical features and the possible effects of apolipoprotein E(APOE) ε4 allele on outer retinal and choroidal alterations in participants with PCA, to detect potential ocular biomarkers for PCA screening. METHODS: This cross-sectional study included PCA and age- and sex-matched healthy control participants from June 2022 to December 2023. All participants with PCA completed a comprehensive neurological evaluation. All participants were recorded baseline information and underwent an ophthalmic evaluation. Quantitative analyses were performed using swept-source optical coherence tomography (SS-OCT) and angiography (SS-OCTA). Adaptive optics scanning laser ophthalmoscopy (AO-SLO) was performed in some patients. In participants with PCA, the influence of APOE ε4 on outer retinal and choroidal alterations and the correlation of outer retinal and choroidal alterations with PCA neuroimaging and clinical features in participants with PCA were investigated. RESULTS: A total of 28 participants (53 eyes) with PCA and 56 healthy control participants (112 eyes) were included in the current study. Compared with healthy control participants, participants with PCA had significantly reduced outer retinal thickness (ORT) (p < 0.001), choriocapillaris vessel density (VD) (p = 0.007), choroidal vascular index (CVI) (p = 0.005) and choroidal vascular volume (CVV) (p = 0.003). In participants with PCA, APOE ε4 carriers showed thinner ORT (p = 0.009), and increased choriocapillaris VD (p = 0.004) and CVI (p = 0.004). The PCA neuroimaging features were positively associated with the ORT, CVI and CVV. Furthermore, differential correlations were observed of PCA clinical features with the CRT, CVV and CVI. CONCLUSIONS: Our findings highlighted the association of outer retinal and choroidal alterations with PCA neuroimaging and clinical features in participants with PCA. Noninvasive SS-OCT and SS-OCTA can provide potential biomarkers for the diagnosis and management of PCA, improving awareness of PCA syndrome among ophthalmologists, neurologists, and primary care providers.

Factors affecting choroidal circulation parameters in 4-14-year-old Chinese children measured by SS-OCT/OCTA.

PURPOSE: To measure the choroidal circulatory parameters Han Chinese children aged 4-14 years from Southwest China, and to explore the relationships between these parameters and age, axial length (AL), and choroidal thickness (ChT). METHODS: 284 eyes from 142 subjects were included in this cross-sectional study. All participants underwent cycloplegic refraction and IOLMaster500 examination. Swept-source optical coherence tomography (SS-OCT) was used to measure submacular choroidal thickness, choroidal vascular volume (CVV), choroidal stromal volume (CSV), choroidal vascularity index (CVI), and CVV/CSV ratio. RESULTS: In this population, the mean CVV was 2.92 ± 0.55 mm3, CSV was 4.69 ± 0.68 mm3, CVI was 38.22 ± 2.46 %, and CVV/CSV ratio was 62.11 ± 6.44 %. Multivariable regression analyses showed that both CVV and CSV were negatively correlated with AL (both P < 0.001) and positively correlated with ChT (both P < 0.001), while age showed no significant correlation with them (both P > 0.05). However, the correlations between CVI and age were not uniform rectilinear. Among participants aged ≤8 years, CVI showed no correlation with age (P > 0.05), while among those aged >8 years, it was positively correlated with age (P < 0.01). CVV/CSV ratio was positively correlated with ChT and age (both P < 0.01). CONCLUSION: After the age of 8, age was positively correlated with CVI. ChT was well correlated with CVI. Longer AL and thinner ChT were associated with reduced CVV and CSV, with CVV decreasing more rapidly than CSV.

Choroidal vascularity index in patients with computer vision syndrome combined with accommodative lead.

BACKGROUND: This study aimed to investigate the choroidal vascularity index (CVI) in patients with computer vision syndrome (CVS) combined with accommodative lead. METHODS: This retrospective case-control study enrolled patients diagnosed with CVS and accommodative lead at University-Town Hospital of Chongqing Medical University between July 2022 and May 2023. The control group included individuals without any ocular diseases. Ophthalmic assessments included basic visual acuity, refraction, ocular biometric parameters, and CVI. RESULTS: A total of 85 participants were included in the study, with 45 in the CVS group and 40 in the control group. The central corneal thickness of CVS group was found to be significantly thinner compared to the control group in both the right eye (532.40±30.93 vs. 545.78±19.99 µm, P = 0.019) and left eye (533.96±29.57 vs. 547.56±20.39, P = 0.014). In comparison to the control group, the CVS group exhibited lower CVI in the superior (0.40±0.08 vs. 0.43±0.09, P = 0.001), temporal (0.40±0.08 vs. 0.44±0.10, P < 0.001), inferior (0.41±0.08 vs. 0.46±0.08, P < 0.001), and nasal (0.41±0.08 vs. 0.44±0.08, P = 0.001) quadrants. Similar differences were observed in all four quadrants within the 1-3 mm radius, and in the temporal (P = 0.004) and inferior (P = 0.002) quadrants within the 1-6 mm and 3-6 mm radii (all P < 0.05). CONCLUSION: Compared to individuals without ocular issues, patients with CVS and accommodative lead were found to have thinner corneal central thickness and lower CVI.

Development of a novel SupraChoroidal-to-Optic-NervE (SCONE) drug delivery system.

PURPOSE: Targeted drug delivery to the optic nerve head may be useful in the preclinical study and later clinical management of optic neuropathies, however, there are no FDA-approved drug delivery systems to achieve this. The purpose of this work was to develop an optic nerve head drug delivery technique. METHODS: Different strategies to approach the optic nerve head were investigated, including standard intravitreal and retroorbital injections. A novel SupraChoroidal-to-Optic-NervE (SCONE) delivery was optimized by creating a sclerotomy and introducing a catheter into the suprachoroidal space. Under direct visualization, the catheter was guided to the optic nerve head. India ink was injected. The suprachoroidal approach was performed in New Zealand White rabbit eyes in vivo (25 animals total). Parameters, including microneedle size and design, catheter design, and catheter tip angle, were optimized ex vivo and in vivo. RESULTS: Out of the candidate optic nerve head approaches, intravitreal, retroorbital, and suprachoroidal approaches were able to localize India ink to within 2 mm of the optic nerve. The suprachoroidal approach was further investigated, and after optimization, was able to deposit India ink directly within the optic nerve head in up to 80% of attempts. In eyes with successful SCONE delivery, latency and amplitude of visual evoked potentials was not different than the naïve untreated eye. CONCLUSIONS: SCONE delivery can be used for targeted drug delivery to the optic nerve head of rabbits without measurable toxicity measured anatomically or functionally. Successful development of this system may yield novel opportunities to study optic nerve head-specific drug delivery in animal models, and paradigm-shifting management strategies for treating optic neuropathies. TRANSLATIONAL RELEVANCE: Here we demonstrate data on a new method for targeted delivery to the optic nerve head, addressing a significant unmet need in therapeutics for optic neuropathies.

Bruch's Membrane Opening Changes in Eyes With Myopic Macular Degeneration: AIER-SERI Adult High Myopia Study.

Purpose: The purpose of this study was to assess the choroidal thickness and the Bruch's membrane opening size and their relationship to visual acuity in eyes with myopic macular degeneration (MMD). Methods: This was a population-based, cross-sectional study. Patients over the age of 30 years with high myopia (spherical equivalent ≤-5 diopters [D]) were recruited. The eyes were grouped according to the International Meta-Analysis for Pathologic Myopia (META-PM) classification based on fundus photographs and diffuse atrophy was subdivided into peripapillary diffuse choroidal atrophy (PDCA) or macular diffuse choroidal atrophy (MDCA). Swept-source optical coherence tomography imaging was performed and then the subfoveal choroidal thickness (SFCT) and Bruch's membrane opening diameter (BMOD) were measured. Results: Of the 470 study participants recruited, 373 patients (691 eyes), with a mean age of 42.8 ± 7.2 years, were eligible for the study and included in the analysis. There was no significant difference in SFCT between MDCA and patchy atrophy (M3) groups (P = 1.000), and the BMOD enlarged significantly from no myopic macular lesions to M3 (the P values of multiple comparison tests were all <0.005). Simple linear regression analysis showed that BMOD correlated positively with age (P < 0.001) and axial length (P < 0.001). Multiple linear regression analysis showed that best corrected visual acuity (BCVA) was significantly correlated with age (P = 0.041), axial length (P = 0.001), and BMOD (P = 0.017), but not with SFCT (P = 0.231). Conclusions: The significant variation of BMOD among MMD groups and the correlation between BMOD and BCVA in MMD eyes suggest that BMOD may be an imaging biomarker for monitoring MMD.

Diurnal gene expression patterns in retina and choroid distinguish myopia progression from myopia onset.

The world-wide prevalence of myopia (nearsightedness) is increasing, but its pathogenesis is incompletely understood. Among many putative mechanisms, laboratory and clinical findings have implicated circadian biology in the etiology of myopia. Consistent with a circadian hypothesis, we recently reported a marked variability in diurnal patterns of gene expression in two crucial tissues controlling post-natal refractive development - the retina and choroid-at the onset of form-deprivation myopia in chick, a widely studied and validated model. To extend these observations, we assayed gene expression by RNA-Seq in retina and choroid during the progression of established unilateral form-deprivation myopia of chick. We assayed gene expression every 4 hours during a single day from myopic and contralateral control eyes. Retinal and choroidal gene expression in myopic vs. control eyes during myopia progression differed strikingly at discrete times during the day. Very few differentially expressed genes occurred at more than one time in either tissue during progressing myopia. Similarly, Gene Set Enrichment Analysis pathways varied markedly by time during the day. Some of the differentially expressed genes in progressing myopia coincided with candidate genes for human myopia, but only partially corresponded with genes previously identified at myopia onset. Considering other laboratory findings and human genetics and epidemiology, these results further link circadian biology to the pathogenesis of myopia; but they also point to important mechanistic differences between the onset of myopia and the progression of established myopia. Future laboratory and clinical investigations should systematically incorporate circadian mechanisms in studying the etiology of myopia and in seeking more effective treatments to normalize eye growth in children.

Optical coherence tomography angiography in thyroid associated ophthalmopathy: a systematic review.

PURPOSE: To evaluate the evidence for alterations of blood flow, vascular and perfusion densities in the choroid, macula, peripapillary region, and the area surrounding the optic nerve head (ONH) in patients with thyroid-associated ophthalmopathy (TAO) based on changes of OCTA parameters. METHODS: A systematic review of Pubmed, Google Scholar, Scopus, WOS, Cochrane, and Embase databases, including quality assessment of published studies, investigating the alterations of OCTA parameters in TAO patients was conducted. The outcomes of interest comprised changes of perfusion and vascular densities in radial peripapillary capillary (RPC), ONH, superficial and deep retinal layers (SRL and DRL), choriocapillaris (CC) flow, and the extent of the foveal avascular zone (FAZ). RESULTS: From the total of 1253 articles obtained from the databases, the pool of papers was narrowed down to studies published until March 20th, 2024. Lastly, 42 studies were taken into consideration which contained the data regarding the alterations of OCTA parameters including choriocapillary vascular flow, vascular and perfusion densities of retinal microvasculature, SRL, and DRL, changes in macular all grid sessions, changes of foveal, perifoveal and parafoveal densities, macular whole image vessel density (m-wiVD) and FAZ, in addition to alterations of ONH and RPC whole image vessel densities (onh-wiVD and rpc-wiVD) among TAO patients. The correlation of these parameters with visual field-associated parameters, such as Best-corrected visual acuity (BCVA), Visual field mean defect (VF-MD), axial length (AL), P100 amplitude, and latency, was also evaluated among TAO patients. CONCLUSION: The application of OCTA has proven helpful in distinguishing active and inactive TAO patients, as well as differentiation of patients with or without DON, indicating the potential promising role of some OCTA measures for early detection of TAO with high sensitivity and specificity in addition to preventing the irreversible outcomes of TAO. OCTA assessments have also been applied to evaluate the effectiveness of TAO treatment approaches, including systemic corticosteroid therapy and surgical decompression.