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Purpose: The purpose of this study was to describe an atypical and severe case of giant cell arteritis (GCA). Methods: This was a case report description. Results: The authors report the case of a 76-year-old man who presented with severe and progressive bilateral visual loss. On presentation at the ophthalmology emergency room, the patient's right eye (OD) displayed aqueous flare, hyphema, rubeosis iridis, and dense posterior capsular opacification. After YAG laser capsulotomy, vitreous densifications, intraretinal hemorrhages, cotton wool spots, retinal ischemia, and vasculitis were observed in the fundoscopy. The patient's left eye (OS) also presented intraretinal hemorrhages and cotton wool spots around the temporal arcades. The diagnostic workup excluded infectious diseases, demyelinating diseases, and ocular ischemic syndrome due to carotid obstruction. Proteinogram revealed a monoclonal gammopathy, suggesting a possible hematologic condition. High-dose corticotherapy was initiated, which improved the vitreous densifications and enabled the visualization of the pale optic disk. The remaining study did not confirm the diagnosis of hematologic disease. During follow-up, bilateral VA deteriorated, with the development of progressive pallor in the OS optic disk. Follow-up fluorescein angiography demonstrated progressive retinal and choroidal ischemia. Finally, owing to high clinical suspicion, temporal artery Doppler ultrasound was performed, confirming the diagnosis of GCA. Conclusion: GCA may present multiple ocular features. The knowledge of these different presentations, including retinal and choroidal ischemia or uveitis, is critical for timely diagnosis and treatment initiation. Since patients with GCA often present with vision loss, ophthalmologists may be the first medical doctors who contact with these patients, being on the frontline of GCA diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: Antiphospholipid syndrome is one of the most common causes of acquired hypercoagulable conditions which is correlated with ocular conditions not least of which is retinal ischemia due to arterial or venous occlusive insults. Case Presentation: We describe a case of unilateral retinal ischemia in the setting of combined central retinal artery and vein occlusion with associated proliferation of retinal pigment epithelium. The patient was worked-up for the etiology of her presentation which was found to be antiphospholipid syndrome. Conclusion: Although pigment epithelial proliferation occurs commonly after retinal ischemia, no study has reported complete multimodal imaging of such a pathology or proposed the possible mechanisms explaining such an association.

Introduction Antiphospholipids syndrome is a rare autoimmune whose Clinical manifestations are very wide and different. Vaso-occlusive manifestations are the most frequent ones. Vessels of all organs can be involved. Ocular involvement is among the rarest. We report a case of retinal arterial thrombosis in the context of APS. Case report A 46-year-old patient with no previous medical history was admitted to the ophthalmology department for visual field amputation of the right eye without other associated signs. On the fundus, the left side was without abnormality and the right side was the site of a mixed arterial and superior temporal venous occlusion. Retinal angiography revealed a retinal focus in the superior temporal region with mixed occlusion of arterial and venous branches with ischemia of the superior temporal quadrant on the right and a retinal focus in the superficial inferior temporal region without occlusion on the left. Optical coherence tomography revealed ischemia of the superficial layers with alteration of the macular microvascularization in the right superior temporal quadrant. Immunological work-up showed antinuclear antibodies to be positive at 160 and anti-bgp1 positive with an IgG level of 118 IgM higher than 118 IgA at 101. The patient was put on effective anticoagulation with good clinical evolution. Conclusion Ocular involvement is rare in APS and associated with poor prognosis, it seems to be difficult to diagnose but also to manage. Larger studies are required to establish guidelines on how and when to screen asymptomatic APS patients for ocular damage, but also on how to prevent and treat it.

This case series describes the aggregate rate of recovery in five consecutive subjects (six eyes) with retinal vein occlusion (RVO) who received l -methylfolate and other vitamins via Ocufolin®, a medical food. Subjects were followed for 10–33 months by a single ophthalmologist. Ocufolin® was prescribed at the time of diagnosis and subjects remained on the regimen throughout the time of observation. Examinations were performed in an un-masked fashion at 3-month intervals with recording of best corrected visual acuity (BCVA), average retinal nerve fiber layer (ARNFL) and central macular thickness (CMT), and fundus (examination of the retina, macula, optic nerve, and vessels) photography. Testing was done for vitamin deficiencies, vascular and coagulable risk factors, and methylenetetrahydrofolate reductase (MTHFR) polymorphisms. Vitamin deficiencies and vascular risk factors were found in all subjects, and all four tested subjects carried at least one MTHFR polymorphism. By the end of the study period BCVA in all subjects was 20/25 or better. Cystoid macular edema was identified and measured by optical coherence tomography (OCT). The percent change was calculated and plotted at 3-month intervals using the percent change in thickness from the time of diagnosis and percent change toward normative values for ARNFL and CMT. The total reduction in thickness of ARNFL and CMT from time of diagnosis was 44.19% and 30.27%, respectively. The comparison to normative data shows a reduction of ARNFL from 164.2% to 94% and CMT from 154.4% to 112.7% of normal thickness (100%). Plots showed the aggregate recovery was most rapid over the first 3 months and slowed over the next 3 months with most of the recovery taking place within 6 months of treatment. The rate of improvement in BCVA and resolution of retinal thickening was found to be better than predicted on historical grounds. No subjects progressed from nonischemic to ischemic RVO. Vitamin deficiencies, vascular risk factors, and genetic predisposition to oxidative stress were common in this RVO series. It appears that addressing these factors with Ocufolin® had a salutary effect on recovery. [ABSTRACT FROM AUTHOR]

IntroductionFew studies have explored MultiColor™ imaging (MCI) in evaluating retinal vascular diseases, particularly branch retinal vein occlusion (BRVO). This study aimed to compare the identification of retinal vessel whitening in BRVO using MCI by scanning confocal laser versus conventional white-flash color fundus photography (CFP).MethodsPaired images of consecutive patients diagnosed with BRVO who underwent same-day MCI and CFP were reviewed. Visualization of vessel whitening on MCI and CFP was graded and scored using a scale by two masked graders. A longitudinal analysis of the vessel grading score was performed to evaluate the vessel whitening detection by MCI. A correlation analysis was conducted between vessel whitening on MCI and the measured area of retinal ischemia on fluorescein angiography to evaluate the MCI performance.ResultsForty-four eyes of 41 patients (mean age 69 ± 14 years; 61% female) were analyzed. MCI demonstrated superior vessel whitening visibility score than CFP (p < 0.001). Longitudinal analysis showed no significant changes in vessel whitening visibility scores over a mean follow-up time of 430 ± 648 days (p = 0.655). There was a significantly positive correlation between the grading score of vessels whitening by MCI and the area of ischemia by fluorescein angiography (r2 = 0.15; p = 0.036).ConclusionMCI appears to provide a superior detection of whitening BRVO compared to CFP, serving as a rapid and non-invasive correlate of retinal ischemia.

Abstract Myeloid cells including microglia and macrophages play crucial roles in retinal homeostasis by clearing cellular debris and regulating inflammation. These cells are activated in several blinding ischemic retinal diseases including diabetic retinopathy, where they may exert both beneficial and detrimental effects on neurovascular function and angiogenesis. Myeloid cells impact the progression of retinal pathologies and recent studies suggest that targeting myeloid cells is a promising therapeutic strategy to mitigate diabetic retinopathy and other ischemic retinal diseases. This review summarizes the recent advances in our understanding of the role of microglia and macrophages in retinal diseases and focuses on the effects of myeloid cells on neurovascular injury and angiogenesis in ischemic retinopathies. We highlight gaps in knowledge and advocate for a more detailed understanding of the role of myeloid cells in retinal ischemic injury to fully unlock the potential of targeting myeloid cells as a therapeutic strategy for retinal ischemia.

Purpose: To evaluate the clinical efficacy of concurrent intravitreal bevacizumab (IVB) injection with trabeculectomy with mitomycin-C (MMC) in neovascular glaucoma (NVG). Methods: Patients with NVG who underwent trabeculectomy with concurrent IVB (group 1) and those who underwent IVB sequentially, followed by trabeculectomy with MMC (group 2) in 1–2 weeks between January 2021 and August 2022, were included in this retrospective hospital-based study. The need for medications for intraocular pressure (IOP) control at 6 months in the two groups was the primary outcome measured and compared between the groups. The association of the need for medications postoperatively with clinical variables was assessed using stepwise multivariate regression statistics. Results: We finally included 40 patients (n = 12 in group 1, n = 28 in group 2) with no significant differences in presenting age between groups. The IOP at 1 day and 1 week were not significantly different between groups though the IOP at 1, 3, and 6 months. IOP was lower in group 1 eyes with the 6-month IOP, being significantly lower in group 1, P = 0.05. Three eyes in group 1 and 11 eyes in group 2 required anti-glaucoma medications in the postoperative period. Multivariate regression identified preoperative IVB >3 (β =0.7, P < 0.001) and recurrent vitreous hemorrhage (β = 0.7, P = 0.004) as prognostic factors (R2 = 40.6%) determining the need for anti-glaucoma medication (AGM) postoperatively in both groups. Conclusion: Concurrent IVB with trabeculectomy with mitomycin-C is a feasible alternative in patients with NVG with refractory high-presenting IOP. This may serve to address raised IOP as well as retinal ischemia, thereby improving surgical success rates in the most challenging NVG cases.

Abstract Introduction There is a high and ever-increasing global prevalence of diabetic retinopathy (DR) and invasive imaging techniques are often required to confirm the presence of proliferative disease. The aim of this study was to explore the images of a rapid and non-invasive technique, widefield optical coherence tomography angiography (OCT-A), to study differences between patients with severe non-proliferative and proliferative DR (PDR). Methods We conducted an observational longitudinal study from November 2022 to March 2023. We recruited 75 patients who were classified into a proliferative group (28 patients) and severe non-proliferative group (47 patients). Classification was done by specialist clinicians who had full access to any multimodal imaging they required to be confident of their diagnosis, including fluorescein angiography. For all patients, we performed single-shot 4 × 4 and 10 × 10 mm (widefield) OCT-A imaging and when possible, the multiple images required for mosaic 17.5 × 17.5 mm (ultra widefield) OCT-A imaging. We assessed the frequency with which proliferative disease was identifiable solely from these OCT-A images and used custom-built MATLAB software to analyze the images and determine computerized metrics such as density and intensity of vessels, foveal avascular zone, and ischemic areas. Results On clinically assessing the OCT-A 10 × 10 fields, we were only able to detect new vessels in 25% of known proliferative images. Using ultra-widefield mosaic images, however, we were able to detect new vessels in 100% of PDR patients. The image analysis metrics of 4 × 4 and 10 × 10 mm images did not show any significant differences between the two clinical groups. For mosaics, however, there were significant differences in the capillary density in patients with PDR compared to severe non-PDR (9.1% ± 1.9 in the PDR group versus 11.0% ± 1.9 for severe group). We also found with mosaics a significant difference in the metrics of ischemic areas; average area of ischemic zones (253,930.1 ± 108,636 for the proliferative group versus 149,104.2 ± 55,101.8 for the severe group. Conclusions Our study showed a high sensitivity for detecting PDR using only ultra-widefield mosaic OCT-A imaging, compared to multimodal including fluorescein angiography imaging. It also suggests that image analysis of aspects such as ischemia levels may be useful in identifying higher risk groups as a warning sign for future conversion to neovascularization.

Purpose: Retinal ischemia is a major feature of diabetic retinopathy (DR). Traditional nonperfused areas measured by OCT angiography (OCTA) measure blood supply but not ischemia. We propose a novel 3-dimensional (3D) quantitative method to derive ischemia measurements from OCTA data. Design: Cross-sectional study. Participants: We acquired 223 macular OCTA volumes from 33 healthy eyes, 33 diabetic eyes without retinopathy, 7 eyes with nonreferable DR, 17 eyes with referable but nonvision-threatening DR, and 133 eyes with vision-threatening DR. Methods: Each eye was scanned using a spectral-domain OCTA system (Avanti RTVue-XR, Visionix/Optovue, Inc) with 1.6-mm scan depth in a 3 × 3-mm region (640 × 304 × 304 voxels) centered on the fovea. For each scanned OCTA volume, a custom algorithm removed flow projection artifacts. We then enhanced, binarized, and skeletonized the vasculature in each OCTA volume and generated a 3D oxygen tension map using a zero-order kinetics oxygen diffusion model. Each volume was scaled to the average retina thickness in healthy controls after foveal registration and flattening of the Bruch's membrane. Finally, we extracted 3D ischemia maps by comparison with a reference map established from scans of healthy eyes using the same processing. To assess the ability of the ischemia maps to grade DR severity, we constructed receiver operating characteristic curves for diagnosing diabetes, referable DR, and vision-threatening DR. Main Outcome Measures: Spearman correlation coefficient and area under receiver operating characteristic curve (AUC) were used to quantify the ability of the ischemia maps to DR. Results: The ischemia maps showed that the ischemic tissues were at or near pathologically nonperfused areas, but not the normally nonvascular tissue, such as the foveal avascular zone. We found multiple novel metrics, including inferred 3D-oxygen tension, ischemia index, and ischemic volume ratio, were strongly correlated with DR severity. The AUCs of ischemia index measured were 0.94 for diabetes, 0.89 for DR, 0.88 for referable DR, and 0.85 for vision-threatening DR. Conclusions: A quantitative method to infer 3D oxygen tension and ischemia using OCTA in diabetic eyes can identify ischemic tissue that are more specific to pathologic changes in DR. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Myeloid cells including microglia and macrophages play crucial roles in retinal homeostasis by clearing cellular debris and regulating inflammation. These cells are activated in several blinding ischemic retinal diseases including diabetic retinopathy, where they may exert both beneficial and detrimental effects on neurovascular function and angiogenesis. Myeloid cells impact the progression of retinal pathologies and recent studies suggest that targeting myeloid cells is a promising therapeutic strategy to mitigate diabetic retinopathy and other ischemic retinal diseases. This review summarizes the recent advances in our understanding of the role of microglia and macrophages in retinal diseases and focuses on the effects of myeloid cells on neurovascular injury and angiogenesis in ischemic retinopathies. We highlight gaps in knowledge and advocate for a more detailed understanding of the role of myeloid cells in retinal ischemic injury to fully unlock the potential of targeting myeloid cells as a therapeutic strategy for retinal ischemia. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical efficacy of concurrent intravitreal bevacizumab (IVB) injection with trabeculectomy with mitomycin-C (MMC) in neovascular glaucoma (NVG). Methods: Patients with NVG who underwent trabeculectomy with concurrent IVB (group 1) and those who underwent IVB sequentially, followed by trabeculectomy with MMC (group 2) in 1–2 weeks between January 2021 and August 2022, were included in this retrospective hospital-based study. The need for medications for intraocular pressure (IOP) control at 6 months in the two groups was the primary outcome measured and compared between the groups. The association of the need for medications postoperatively with clinical variables was assessed using stepwise multivariate regression statistics. Results: We finally included 40 patients (n = 12 in group 1, n = 28 in group 2) with no significant differences in presenting age between groups. The IOP at 1 day and 1 week were not significantly different between groups though the IOP at 1, 3, and 6 months. IOP was lower in group 1 eyes with the 6-month IOP, being significantly lower in group 1, P = 0.05. Three eyes in group 1 and 11 eyes in group 2 required anti-glaucoma medications in the postoperative period. Multivariate regression identified preoperative IVB >3 (β =0.7, P < 0.001) and recurrent vitreous hemorrhage (β = 0.7, P = 0.004) as prognostic factors (R2 = 40.6%) determining the need for anti-glaucoma medication (AGM) postoperatively in both groups. Conclusion: Concurrent IVB with trabeculectomy with mitomycin-C is a feasible alternative in patients with NVG with refractory high-presenting IOP. This may serve to address raised IOP as well as retinal ischemia, thereby improving surgical success rates in the most challenging NVG cases. [ABSTRACT FROM AUTHOR]

Introduction: There is a high and ever-increasing global prevalence of diabetic retinopathy (DR) and invasive imaging techniques are often required to confirm the presence of proliferative disease. The aim of this study was to explore the images of a rapid and non-invasive technique, widefield optical coherence tomography angiography (OCT-A), to study differences between patients with severe non-proliferative and proliferative DR (PDR). Methods: We conducted an observational longitudinal study from November 2022 to March 2023. We recruited 75 patients who were classified into a proliferative group (28 patients) and severe non-proliferative group (47 patients). Classification was done by specialist clinicians who had full access to any multimodal imaging they required to be confident of their diagnosis, including fluorescein angiography. For all patients, we performed single-shot 4 × 4 and 10 × 10 mm (widefield) OCT-A imaging and when possible, the multiple images required for mosaic 17.5 × 17.5 mm (ultra widefield) OCT-A imaging. We assessed the frequency with which proliferative disease was identifiable solely from these OCT-A images and used custom-built MATLAB software to analyze the images and determine computerized metrics such as density and intensity of vessels, foveal avascular zone, and ischemic areas. Results: On clinically assessing the OCT-A 10 × 10 fields, we were only able to detect new vessels in 25% of known proliferative images. Using ultra-widefield mosaic images, however, we were able to detect new vessels in 100% of PDR patients. The image analysis metrics of 4 × 4 and 10 × 10 mm images did not show any significant differences between the two clinical groups. For mosaics, however, there were significant differences in the capillary density in patients with PDR compared to severe non-PDR (9.1% ± 1.9 in the PDR group versus 11.0% ± 1.9 for severe group). We also found with mosaics a significant difference in the metrics of ischemic areas; average area of ischemic zones (253,930.1 ± 108,636 for the proliferative group versus 149,104.2 ± 55,101.8 for the severe group. Conclusions: Our study showed a high sensitivity for detecting PDR using only ultra-widefield mosaic OCT-A imaging, compared to multimodal including fluorescein angiography imaging. It also suggests that image analysis of aspects such as ischemia levels may be useful in identifying higher risk groups as a warning sign for future conversion to neovascularization. [ABSTRACT FROM AUTHOR]

Retinal ischemia plays a vital role in vision-threatening retinal ischemic disorders, such as diabetic retinopathy, age-related macular degeneration, glaucoma, etc. The aim of this study was to investigate the effects of S-allyl L-cysteine (SAC) and its associated therapeutic mechanism. Oxidative stress was induced by administration of 500 μM H2O2 for 24 h; SAC demonstrated a dose-dependent neuroprotective effect with significant cell viability effects at 100 μM, and it concurrently downregulated angiogenesis factor PKM2 and inflammatory biomarker MCP-1. In a Wistar rat model of high intraocular pressure (HIOP)-induced retinal ischemia and reperfusion (I/R), post-administration of 100 μM SAC counteracted the ischemic-associated reduction of ERG b-wave amplitude and fluorogold-labeled RGC reduction. This study supports that SAC could protect against retinal ischemia through its anti-oxidative, anti-angiogenic, anti-inflammatory, and neuroprotective properties. [ABSTRACT FROM AUTHOR]

Retinal ischemia is a common clinical event leading to retinal ganglion cell (RGC) death, resulting in irreversible vision loss. In the retina, glia-neuron communication is crucial for multiple functions and homeostasis. Extracellular vesicles, notably exosomes, play a critical role. The functions and mechanisms of retinal astrocyte-secreted exosomes remain unclear. Here, we isolated astrocyte-derived exosomes under hypoxia or normoxia and explored their role in an in vivo retinal ischemia-reperfusion (RIR) model. We found that hypoxia triggered astrocytes to produce a significantly increased number of exosomes, which could be internalized by RGCs in vivo or in vitro. Also, in the RIR model, the hypoxia-induced exosomes ameliorated the RIR injury and suppressed the RGC apoptosis. Furthermore, microRNA sequencing of retinal astrocyte-secreted exosomes revealed different patterns of exosomal miRNAs under hypoxia, particularly enriched with miR-329-5p. We verified that miR-329-5p was specifically bound to mitogen-activated protein kinase 8 mRNA, and subsequent JNK-pathway molecules were downregulated. We anticipated that the miR-329-5p/JNK pathway is a key to suppressing RGC apoptosis and preventing RIR injury. Such findings provided insights into the therapeutic potential of hypoxia-induced astrocyte-secreted exosomes and the miR-329-5p for treating retina ischemic diseases.

Introduction: Retinopathy of prematurity (ROP) is a vasoproliferative disease that alters retinal vascular patterns in preterm neonates with immature retinal vasculature. This study was conducted to investigate the effects of cell therapy by bone marrow mononuclear cells (BMMNC) on neurological and vascular damages in a rat model of ROP. Methods: Ten newborn Wistar rats were divided randomly into the control and the oxygen-induced retinopathy (OIR) groups. Animals in the OIR group were incubated in an oxygen chamber to induce retinopathy. One eye of animals in the OIR group received BMMNC suspension (treated eyes), and the contralateral eye received the same volume of saline injection. Then, all animals underwent funduscopy, angiography, electroretinography, histopathology and immunohistochemical assessments. Results: Compared to the saline injection group, eyes treated with BMMNC had less vascular tortuosity while veins and arteries had relatively the same caliber, as revealed by fundus examinations. Eyes in the treatment group showed significantly elevated photopic and scotopic B waves amplitude. Neovascularization in the inner retinal layer and apoptosis of neural retina cells in the treatment group was significantly lower compared to untreated eyes. Also, BMMNC transplantation decreased glial cell activation and VEGF expression in ischemic retina. Conclusions: Our results indicate that intravitreal injection of BMMNC reduces neural and vascular damages and results in recovered retinal function in rat model of ROP. Ease of extraction without in vitro processing, besides the therapeutic effects of BMMNCs, make this source of cells as a new choice of therapy for ROP or other retinal ischemic diseases.

Introduction:Central retinal artery occlusion (CRAO) is an under-recognized stroke subtype that may benefit from hyperacute reperfusion therapies. We aimed to evaluate the ability of telestroke activations to provide CRAO diagnosis and thrombolysis. Methods:This retrospective observational study investigates all encounters conducted for acute visual loss between 2010 and 2021 in our multicentric Mayo Clinic Telestroke Network. Demographics, time from visual loss to telestroke evaluation, ocular examination, diagnostic, and therapeutic recommendations were collected for CRAO subjects. Results:Out of 9,511, 49 encounters (0.51%) were conducted for an acute ocular complaint. Five patients had possible CRAO, and 4 presented within 4.5 h from symptom onset (range 1.5–5 h). None received thrombolytic therapy. All telestroke physicians recommended ophthalmology consultation. Conclusion:Current telestroke assessment of acute visual loss is suboptimal and patients eligible for acute reperfusion therapies may not be offered treatment. Teleophthalmologic evaluations and advanced ophthalmic diagnostic tools should complement telestroke systems. [ABSTRACT FROM AUTHOR]

PurposeMyopic macular degeneration (MMD) can cause irreversible vision loss. Thinner choroid is associated with increased MMD severity. This cross-sectional study analyzed choriocapillaris (CC) alterations in MMD.MethodsAxial length (AL), best-corrected visual acuity (BCVA), fundus photography, and swept-source optical coherence tomography angiography (SS-OCTA) were assessed in controls and high myopes (spherical equivalent ≤ -6 diopters). Myopic patients with grade 2 MMD (macular diffuse chorioretinal atrophy [MDCA]), high axial myopia (AL ≥ 26.5 mm), and BCVA ≥ 20/40 were compared with controls without MMD. CC mean thickness was measured from 3 × 3-mm SS-OCTA scans by identifying CC peaks in A-scan intensity profiles. CC flow deficit percent (CC FD%) was quantified using a fuzzy C-mean local thresholding method on en face OCTA images. Multivariate regressions compared CC thickness and CC FD% between myopic patients and controls, correcting for age and other confounders.ResultsSixteen eyes with MDCA (AL, 26.96-33.93 mm; ages, 40-78 years) were compared with 51 control eyes (AL, 21.65-25.84 mm; ages, 19-88 years). CC thickness in patients with MDCA was 66% lower than that in controls (5.23 ± 0.68 µm [mean ± SD] vs. 15.46 ± 1.82 µm; P < 0.001). CC FD% in patients with MDCA was 237% greater than in controls (26.5 ± 4.3 vs. 11.2 ± 4.6; P < 0.001).ConclusionsPatients with MDCA with good visual acuity had thinner CC and increased CC FD%, or reduced CC flow, compared with controls. Patients with grade 2 MMD and good visual acuity demonstrated significant choriocapillaris alterations, suggesting that choriocapillaris perfusion defects contribute to the pathogenesis of MMD.Translational relevanceGiven the potential vascular etiology for MMD, current research about revascularization of ischemic retina likely has implications for the treatment of MMD.

Haoxin Guo,1,&ast; Wenbo Li,1,&ast; Kuan Wang,1,2 Zetong Nie,1 Xiang Zhang,1 Siqiong Bai,1 Naxin Duan,1 Xiaorong Li,1 Bojie Hu1 1Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin University Eye Hospital, Tianjin, People’s Republic of China; 2Cangzhou Eye Hospital, Cangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bojie Hu, Email bhu07@tmu.edu.cnPurpose: We aimed to investigate the risk factors associated with revitrectomy in eyes with diabetic vitreous hemorrhage and to determine the prognosis of these patients at least one year postoperatively.Patients and Methods: This retrospective case-control study had a minimum follow-up period of one year. Patients were divided into single vitrectomy group (control group, n=202) and revitrectomy group (case group, n=36) for analysis. The indications, number, and timing of revitrectomies were documented. And the revitrectomy group was further divided into two vitrectomies group (n=30) and three or more vitrectomies group (n=6). The best-corrected visual acuity (BCVA) at the last follow-up and the occurrence of neovascular glaucoma (NVG) were compared among the single vitrectomy, two vitrectomies and three or more vitrectomies groups. We conducted a thorough collection of patient data and used univariate and binary logistic regression analyses to identify the risk factors associated with revitrectomy.Results: A total of 197 patients (238 eyes) were included. Thirty-six eyes (15.1%) required revitrectomy with six eyes (2.5%) undergoing three or more vitrectomies during the follow-up period. The median duration of the second vitrectomy was 3 (2– 6) months. The indications for a second vitrectomy included 28 eyes (77.8%) of postoperative vitreous hemorrhage and 7 eyes (22.2%) combined with tractional retinal detachment. Patients undergoing three or more vitrectomies had significantly worse postoperative BCVA and a higher incidence of NVG (P< 0.01). Fibrinogen> 4 g/L (P< 0.001) and preoperative anti-vascular endothelial growth factor intravitreal injection (P=0.015) were independent risk factors for revitrectomy, and glycated hemoglobin A1c (HbA1c)> 10% (P=0.049) showed significant difference only in univariate analysis.Conclusion: Patients requiring revitrectomy tended to have higher fibrinogen levels, tightly adhered fibrovascular membranes, higher HbA1c levels, and worse prognoses.Keywords: proliferative diabetic retinopathy, vitreous hemorrhage, revitrectomy, fibrinogen, retinal ischemia

Abstract Purpose To investigate the association between retinal vein occlusion (RVO) and evidence of previous, unnoticed inner nuclear layer (INL) infarction in the fellow eye. Methods This prospective case-control study compared the prevalence of INL lesions in the fellow eye of consecutive people with hypertension (PwHTN) with unilateral RVO versus a randomly chosen eye of an age-matched control group of PwHTN without RVO. En face slabs above the outer plexiform layer (OPL) were generated from 6 × 6 fovea-centered optical coherence tomography scans. Cross-sectional scans and en face slabs were surveyed for evidence of active/resolved ischemic INL lesions. Results 69 PwHTN were included and assigned to two groups, i.e., the RVO group (n = 37; 22 BRVO and 15 CRVO) and the control group (n = 32). There was no inter-group difference regarding age, gender distribution, and background diseases. Resolved INL lesions were more frequent in the RVO group (n = 26) than in the control group (n = 4) (70.3% vs. 12.5%, p

Abstract Background Reduced folate carrier 1 (RFC1; SLC19a1) is the main responsible transporter for the B9 family of vitamins named folates, which are essential for normal tissue growth and development. While folate deficiency resulted in retinal vasculopathy, the expression and the role of RFC1 in blood-retinal barrier (BRB) are not well known. Methods We used whole mount retinas and trypsin digested microvessel samples of adult mice. To knockdown RFC1, we delivered RFC1-targeted short interfering RNA (RFC1-siRNA) intravitreally; while, to upregulate RFC1 we delivered lentiviral vector overexpressing RFC1. Retinal ischemia was induced 1-h by applying FeCl3 to central retinal artery. We used RT-qPCR and Western blotting to determine RFC1. Endothelium (CD31), pericytes (PDGFR-beta, CD13, NG2), tight-junctions (Occludin, Claudin-5 and ZO-1), main basal membrane protein (Collagen-4), endogenous IgG and RFC1 were determined immunohistochemically. Results Our analyses on whole mount retinas and trypsin digested microvessel samples of adult mice revealed the presence of RFC1 in the inner BRB and colocalization with endothelial cells and pericytes. Knocking down RFC1 expression via siRNA delivery resulted in the disintegration of tight junction proteins and collagen-4 in twenty-four hours, which was accompanied by significant endogenous IgG extravasation. This indicated the impairment of BRB integrity after an abrupt RFC1 decrease. Furthermore, lentiviral vector-mediated RFC1 overexpression resulted in increased tight junction proteins and collagen-4, confirming the structural role of RFC1 in the inner BRB. Acute retinal ischemia decreased collagen-4 and occludin levels and led to an increase in RFC1. Besides, the pre-ischemic overexpression of RFC1 partially rescued collagen-4 and occludin levels which would be decreased after ischemia. Conclusion In conclusion, our study clarifies the presence of RFC1 protein in the inner BRB, which has recently been defined as hypoxia–immune-related gene in other tissues and offers a novel perspective of retinal RFC1. Hence, other than being a folate carrier, RFC1 is an acute regulator of the inner BRB in healthy and ischemic retinas.

An ophthalmology consultation was requested for a 29-year-old woman complaining of visual field defects. The patient had presented to the emergency department with cough and high fever one day earlier. Chest computed tomography demonstrated pneumonia and two severe acute respiratory syndrome coronavirus 2 polymerase chain reaction tests were positive. The patient had undergone renal transplantation 11 years ago due to glomerulonephritis. Best-corrected visual acuity (BCVA) was 20/40 in the right eye and 20/30 in the left eye. Fluorescein angiography showed macular hypoperfusion, and optical coherence tomography (OCT) showed hyperreflectivity in the inner nuclear, outer plexiform, and outer nuclear layers, as well as discontinuity of the ellipsoid zone. Perimetry confirmed bilateral central scotoma. Levels of D-dimer and fibrinogen were 0.86 g/mL and 435.6 g/mL, respectively. The patient was diagnosed as having concurrent acute macular neuroretinopathy and paracentral acute middle maculopathy and was given low-molecular-weight heparin treatment for one month. Her BCVA improved to 20/20 in both eyes, and regression was observed in the retinal findings, hyperreflectivity and ellipsoid zone disruption on OCT, and scotoma in perimetry. Inflammation, thrombosis, and glial involvement may play a role in the pathogenesis of retinal microvascular impairment in COVID-19.

Serum response factor (SRF) controls the expression of muscle contraction and motility genes in mural cells (MCs) of the vasculature. In the retina, MC-SRF is important for correct angiogenesis during development and the continuing maintenance of the vascular tone. The purpose of this study was to provide further insights into the effects of MC SRF deficiency on the vasculature and function of the mature retina in SrfiMCKO mice that carry a MC-specific deletion of Srf. Retinal morphology and vascular integrity were analyzed in vivo via scanning laser ophthalmoscopy (SLO), angiography, and optical coherence tomography (OCT). Retinal function was evaluated with full-field electroretinography (ERG). We found that retinal blood vessels of these mutants exhibited different degrees of morphological and functional alterations. With increasing severity, we found vascular bulging, the formation of arteriovenous (AV) anastomoses, and ultimately, a retinal detachment (RD). The associated irregular retinal blood pressure and flow distribution eventually induced hypoxia, indicated by a negative ERG waveform shape. Further, the high frequency of interocular differences in the phenotype of individual SrfiMCKO mice points to a secondary nature of these developments far downstream of the genetic defect and rather dependent on the local retinal context. [ABSTRACT FROM AUTHOR]

Endothelin-1 (ET-1) overactivity has been implicated as a factor contributing to glaucomatous neuropathy, and it has been utilized in animal models of retinal ischemia. The functional effects of long-term ET-1 exposure and possible compensatory mechanisms have, however, not been investigated. This was therefore the purpose of our study. ET-1 was delivered into rat eyes via a single intravitreal injection of 500 µM or via transgene delivery using an adeno-associated viral (AAV) vector. Retinal function was assessed using electroretinography (ERG) and the retinal expression of potentially compensatory genes was evaluated by means of qRT-PCR. Acute ET-1 delivery led to vasoconstriction and a significant reduction in the ERG response. AAV–ET-1 resulted in substantial transgene expression and ERG results similar to the acute ET-1 injections and comparable to other models of retinal ischemia. Compensatory changes were observed, including an increase in calcitonin gene-related peptide (CGRP) gene expression, which may both counterbalance the vasoconstrictive effects of ET-1 and provide neuroprotection. This chronic ET-1 ischemia model might be especially relevant to glaucoma research, mimicking the mild and repeated ischemic events in patients with long-term vascular dysfunction. The compensatory mechanisms, and particularly the role of vasodilatory CGRP in mitigating the retinal damage, warrant further investigation with the aim of evaluating new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Neovascular glaucoma (NVG) is a sight-threatening condition that is often refractory to treatment. Current management principles are yet to be standardized due to lack of evidence. We studied the interventions used to treat NVG at Sydney Eye Hospital (SEH) and the two-year surgical outcomes. Methods: We performed a retrospective audit of 67 eyes of 58 patients with NVG from January 1, 2013, to December 31, 2018. Intraocular pressure (IOP), best-corrected visual acuity (BCVA), number of medications, repeat surgery, recurrent neovascularization, loss of light perception and pain were studied. Results: The average age of the cohort was 59.67 years (SD 14.22). The most common etiologies were proliferative diabetic retinopathy (35 eyes; 52.2%), central retinal vein occlusion (18 eyes; 26.9%) and ocular ischemic syndrome (7 eyes; 10.4%). 70.1% of eyes (47) received vascular endothelial growth factor injections (VEGFI), 41.8% (28 eyes) received pan-retinal photocoagulation (PRP) and 37.3% (25 eyes) received both prior to or within the first week of presentation to SEH. The most common initial surgical interventions were trans-scleral cyclophotocoagulation (TSCPC) (36 eyes; 53.7%) and Baerveldt tube insertion (18 eyes; 26.9%). 62.7% of eyes (42 eyes) failed (IOP > 21 or < 6 mmHg for two consecutive reviews, further IOP-lowering surgery or loss of light perception) during follow-up. Initial TSCPC failed in 75.0% (27/36 eyes) compared with 44.4% (8/18 eyes) after Baerveldt tube insertion. Conclusion: Our study reinforces the refractory nature of NVG, often despite intensive treatment and surgery. Improvements in patient outcomes may be achieved with earlier consideration of VEGFI and PRP. This study identifies the limitations of surgical interventions for NVG and highlights the need for a standardized management approach. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the association between retinal vein occlusion (RVO) and evidence of previous, unnoticed inner nuclear layer (INL) infarction in the fellow eye. Methods: This prospective case-control study compared the prevalence of INL lesions in the fellow eye of consecutive people with hypertension (PwHTN) with unilateral RVO versus a randomly chosen eye of an age-matched control group of PwHTN without RVO. En face slabs above the outer plexiform layer (OPL) were generated from 6 × 6 fovea-centered optical coherence tomography scans. Cross-sectional scans and en face slabs were surveyed for evidence of active/resolved ischemic INL lesions. Results: 69 PwHTN were included and assigned to two groups, i.e., the RVO group (n = 37; 22 BRVO and 15 CRVO) and the control group (n = 32). There was no inter-group difference regarding age, gender distribution, and background diseases. Resolved INL lesions were more frequent in the RVO group (n = 26) than in the control group (n = 4) (70.3% vs. 12.5%, p < 0.001). BRVO and CRVO cases had similar prevalence of INL lesions in their fellow eyes. Unlike diabetes, ischemic heart disease, and gender, INL lesions were associated with RVO (in the fellow eye) with an odds ratio of 15.7 (95%CI: 4.17–76.73, p < 0.001). Conclusion: We identified a substantially higher prevalence of INL lesions in PwHTN with RVO compared to PwHTN without RVO. The atrophic appearance of lesions suggests they may serve as early markers of increased RVO risk in individuals with systemic or cardiovascular predisposing factors. [ABSTRACT FROM AUTHOR]

Recently, stable gastric pentadecapeptide BPC 157 therapy by activation of collateral pathways counteracted various occlusion/occlusion-like syndromes, vascular, and multiorgan failure, and blood pressure disturbances in rats with permanent major vessel occlusion and similar procedures disabling endothelium function. Thereby, we revealed BPC 157 cytoprotective therapy with strong vascular rescuing capabilities in glaucoma therapy. With these capabilities, BPC 157 therapy can recover glaucomatous rats, normalize intraocular pressure, maintain retinal integrity, recover pupil function, recover retinal ischemia, and corneal injuries (i.e., maintained transparency after complete corneal abrasion, corneal ulceration, and counteracted dry eye after lacrimal gland removal or corneal insensitivity). The most important point is that in glaucomatous rats (three of four episcleral veins cauterized) with high intraocular pressure, all BPC 157 regimens immediately normalized intraocular pressure. BPC 157-treated rats exhibited normal pupil diameter, microscopically well-preserved ganglion cells and optic nerve presentation, normal fundus presentation, nor- mal retinal and choroidal blood vessel presentation, and normal optic nerve presentation. The one episcleral vein rapidly upgraded to accomplish all functions in glaucomatous rats may correspond with occlusion/occlusion-like syndromes of the activated rescuing collateral pathway (azygos vein direct blood flow delivery). Normalized intraocular pressure in glaucomatous rats corresponded to the counteracted intra-cranial (superior sagittal sinus), portal, and caval hypertension, and aortal hypotension in occlusion/occlusion-like syndromes, were all attenuated/eliminated by BPC 157 therapy. Furthermore, given in other eye disturbances (i.e., retinal ischemia), BPC 157 instantly breaks a noxious chain of events, both at an early stage and an already advanced stage. Thus, we further advocate BPC 157 as a therapeutic agent in ocular disease. [ABSTRACT FROM AUTHOR]

Paracentral acute middle maculopathy (PAMM) is an optical coherence tomography (OCT) finding secondary to retinal ischemia. In this presentation, we describe the diagnosis of hereditary thrombophilia caused by multiple gene mutation, based on the PAMM finding on OCT, in a patient with no known disease who presented with unilateral scotoma. Hematological evaluation has an important role in young PAMM cases without systemic and ocular disease. Patients with thrombophilic mutations may be first recognized with ocular symptoms by ophthalmologists. It may be life-saving to reveal the risks of patients such as cardiovascular disease and thromboembolism at an early age. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by arterial and venous thrombosis. Early diagnosis and initiation of thromboprophylaxis reduce the risk of recurrent thrombosis. In this report, we presented a case with no known systemic disease but diagnosed as primary APS based on retinal ischemia findings in fluorescein angiography and optic coherence tomography angiography. The aim of this report is to emphasize that APS, which causes thrombosis in vital organs, can occur with retinal ischemia and that the diagnosis of the disease by an ophthalmologist can be life-saving. [ABSTRACT FROM AUTHOR]

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Key Clinical Message CRAO is an ophthalmic and medical emergency. This case is a reminder that diagnosis and management of CRAO begins with ophthalmologists but immediately thereafter care involves emergency cardiovascular and neurological similar to cerebral stroke.

Background: Reduced folate carrier 1 (RFC1; SLC19a1) is the main responsible transporter for the B9 family of vitamins named folates, which are essential for normal tissue growth and development. While folate deficiency resulted in retinal vasculopathy, the expression and the role of RFC1 in blood-retinal barrier (BRB) are not well known. Methods: We used whole mount retinas and trypsin digested microvessel samples of adult mice. To knockdown RFC1, we delivered RFC1-targeted short interfering RNA (RFC1-siRNA) intravitreally; while, to upregulate RFC1 we delivered lentiviral vector overexpressing RFC1. Retinal ischemia was induced 1-h by applying FeCl3 to central retinal artery. We used RT-qPCR and Western blotting to determine RFC1. Endothelium (CD31), pericytes (PDGFR-beta, CD13, NG2), tight-junctions (Occludin, Claudin-5 and ZO-1), main basal membrane protein (Collagen-4), endogenous IgG and RFC1 were determined immunohistochemically. Results: Our analyses on whole mount retinas and trypsin digested microvessel samples of adult mice revealed the presence of RFC1 in the inner BRB and colocalization with endothelial cells and pericytes. Knocking down RFC1 expression via siRNA delivery resulted in the disintegration of tight junction proteins and collagen-4 in twenty-four hours, which was accompanied by significant endogenous IgG extravasation. This indicated the impairment of BRB integrity after an abrupt RFC1 decrease. Furthermore, lentiviral vector-mediated RFC1 overexpression resulted in increased tight junction proteins and collagen-4, confirming the structural role of RFC1 in the inner BRB. Acute retinal ischemia decreased collagen-4 and occludin levels and led to an increase in RFC1. Besides, the pre-ischemic overexpression of RFC1 partially rescued collagen-4 and occludin levels which would be decreased after ischemia. Conclusion: In conclusion, our study clarifies the presence of RFC1 protein in the inner BRB, which has recently been defined as hypoxia–immune-related gene in other tissues and offers a novel perspective of retinal RFC1. Hence, other than being a folate carrier, RFC1 is an acute regulator of the inner BRB in healthy and ischemic retinas. [ABSTRACT FROM AUTHOR]

Takayasu's arteritis (TA) is a type of vasculitis in which inflammation develops in large vessels, especially in the aorta and its branches. Our study aims to determine the prevalence and type of ocular manifestations in TA. A systematic literature search was conducted in December 2022 using three electronic databases (PubMed, Scopus, and Web of Science). The following data were extracted from each article: the name of the first author; the patient's age, sex, and origin (continent); circumstances connected with the diagnosis of TA; symptoms given by the patients; reported ocular manifestations; and administered treatment. The final analysis was based on data collected from 122 cases. Retinal ischemia, followed by optic neuropathy, cataract, and retinal artery occlusion, were the most prevalent eye conditions associated with the disease. Systemic steroid therapy, vascular procedures, and methotrexate were mainly used to treat pulseless disease. Patients mostly complained of gradual vision acuity loss, sudden vision acuity loss, ocular pain, and amaurosis fugax. The diagnosis of Takayasu's arteritis should be considered in patients presenting symptoms of visual decline/loss, ocular pain, or signs of retinal ischemia, optic neuropathy, or early cataract formation. A proper diagnosis is crucial to ensure the patient receives treatment without significant delay. [ABSTRACT FROM AUTHOR]

Retinal complications in patients with inflammatory optic neuritis (ON) are generally related to post-infectious neuroretinitis and are considered uncommon in autoimmune/demyelinating ON, whether isolated or caused by multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD). More recently, however, cases with retinal complications have been reported in subjects positive for myelin oligodendrocyte glycoprotein (MOG) antibodies. We report a 53-year-old woman presenting with severe bilateral ON associated with a focal area of paracentral acute middle maculopathy (PAMM) in one eye. Visual loss recovered remarkably after high-dose intravenous corticosteroid treatment and plasmapheresis, but the PAMM lesion remained visible on both optical coherence tomography and angiography as an ischaemic lesion affecting the middle layers of the retina. The report emphasises the possible occurrence of retinal vascular complications in MOG–related optic neuritis, an important addition to the diagnosis of, and possible differentiation from, MS–related or NMOSD–related ON. [ABSTRACT FROM AUTHOR]

Retinal ischemia–reperfusion (RIR) injury caused by high intraocular pressure (IOP) is an important risk factor contributing to retinal ganglion cell (RGC) death, eventually causing blindness. A key progressive pathological process in the development of RIR is the death of RGCs. However, the detailed mechanisms underlying RGC death caused by RIR have not yet been clearly elucidated, and effective treatments are lacking. Ferroptosis is a recently defined form of programmed cell death that is closely related to organ injury. Melatonin (MT) is a promising neuroprotective agent, but its effects on RIR injury remain unclear. In this study, murine models of acute ocular hypertension and oxygen and glucose deprivation/reoxygenation (OGD/R) model were adopted to simulate retinal ischemia. MT alleviated retinal damage and RGC death in RIR mice, significantly attenuating RIR–induced ferroptosis. Furthermore, MT reduced the expression of p53, a master regulator of ferroptosis pathways, and the upregulation of p53 promoted ferroptosis and largely abolished the neuroprotective effects of MT. Mechanistically, the overexpression (OE) of p53 suppressed the expression of the solute carrier family 7 member 11 (Slc7a11), which was accompanied by increased 12–lipoxygenase (Alox12) expression, triggering retinal ferroptosis. Moreover, MT–ameliorated apoptosis, neuroinflammation and microglial activation were observed. In summary, MT conferred neuroprotection against RIR injury by inhibiting p53–mediated ferroptosis. These findings indicate that MT is a retina–specific ferroptosis inhibitor and a promising therapeutic agent for retinal neuroprotection. [ABSTRACT FROM AUTHOR]

Branch retinal vein occlusions are a significant cause of vision loss and present several ophthalmic and systemic risk factors, including age, hypertension, hyperlipidemia and glaucoma. Retinal vein occlusion is the second-most-common retinal vascular disease. This study evaluated the effects of Ozurdex in contrast to a combination therapy with anti-vascular endothelial growth factor (VEGF) and cortisone in treatment-naive branch retinal vein occlusions-macular edema (BRVO-ME) cases, at 4-month and 6-month follow-ups. Thirty eyes were included in the study, which were divided into two groups. The first group consisted of 15 eyes, and each received 1 injection of dexamethasone intravitreal implant Ozurdex (DEX). The second group of 15 eyes received 3 intravitreal injections, the first and second with the anti-vascular endothelial growth factor aflibercept and the third one with 4 mg of triamcinolone acetonide (Vitreal S), spaced at one month. The best corrected visual acuity (BCVA) results suggested that the peak efficacy was at 4 months for both groups, with mean values of 0.5 LogMAR and 0.4 LogMAR. Regarding macular edema, there were no significant changes between the 4- and 6-month follow-up periods, with mean values of 361 μm and 390 μm. Six patients experienced transient raised intraocular pressure at one week after treatment. This study highlights the benefits to visual acuity of the combination of anti-vascular endothelial growth factor and cortisone, which represents a viable solution with similar results to Ozurdex therapy. [ABSTRACT FROM AUTHOR]

Ischemic retinal damage, a common condition associated with retinal vascular occlusion, glaucoma, diabetic retinopathy, and other eye diseases, threatens the vision of millions of people worldwide. It triggers excessive inflammation, oxidative stress, apoptosis, and vascular dysfunction, leading to the loss and death of retinal ganglion cells. Unfortunately, minority drugs are available for treating retinal ischemic injury diseases, and their safety are limited. Therefore, there is an urgent need to develop more effective treatments for ischemic retinal damage. Natural compounds have been reported to have antioxidant, anti-inflammatory, and antiapoptotic properties that can be used to treat ischemic retinal damage. In addition, many natural compounds have been shown to exhibit biological functions and pharmacological properties relevant to the treatment of cellular and tissue damage. This article reviews the neuroprotective mechanisms of natural compounds involve treating ischemic retinal injury. These natural compounds may serve as treatments for ischemia-induced retinal diseases. [ABSTRACT FROM AUTHOR]

Retinal ischemia gives rise to a complex spectrum in which the cumulative profile of ischemia of the middle and inner retina can be highly variable. We reviewed the current knowledge on paracentral acute middle maculopathy (PAMM) pathophysiology and accompanying risk factors, the middle and inner retinal vasculature and blood flow, and the vulnerability of the middle retina in vaso-occlusive disorders. The inner nuclear layer (INL) is easily affected by slight degrees of retinal hypoperfusion and ischemia. INL infarction starts at perivenular sites, manifesting as skip PAMM lesions and a fern-like appearance in cross-sectional and en face views, respectively. With horizontal progression, INL infarction may develop into diffuse globular PAMM. If vertical progression occurs, the entire middle and inner portions of the retina can be affected. Transmural infarction of the middle and inner retina would be at the end of this spectrum. This gradient of ischemic progression resembles an ischemic cascade. We review the evidence supporting the term "retinal ischemic cascade," which encompasses a broad continuum of manifestations with roots in middle retinal infarction. With this terminology, variations in spatial and temporal progression and resolution of ischemia can also be delivered; it further enables addressing the possible associations between the middle and inner retinal ischemic patterns. [ABSTRACT FROM AUTHOR]

Glaucoma is one of the most common sight-threatening eye disorders and one of the main causes of irreversible blindness worldwide. The current therapies focusing on reducing intraocular pressure (IOP) are often insufficient to prevent the progression of the disease, so the therapeutic management of glaucoma remains a challenge. The aim of this study was to evaluate the neuroprotective, IOP-lowering independent effects of a nutritional supplement containing forskolin, homotaurine, spearmint extract and vitamins of the B group in a model of acute glaucoma developed in mice. Glaucoma was induced in adult wild-type C57BL/6J mice by transient elevation of IOP. The dietary supplement, branded as Gangliomix® (125 mg/kg/day), was administered by oral gavage for 17 days and ocular hypertension was induced on the 10th day of treatment. A histological analysis of the retinas was performed and RGC survival was evaluated with fluorogold labeling and Brn3a immunostaining on wholemount and retinal sections. Expression of alpha-spectrin, caspase-3, PARP-1 and GFAP was studied with western blotting or immunofluorescence. A significant increase in RGC survival was reported in the retina of mice treated with the dietary supplement as compared to vehicle-treated animals. The observed neuroprotection was associated with a calpain activity decrease, reduction in caspase-3 and PARP-1 activation, and prevention of GFAP upregulation. These effects were independent from the hypotensive effects of the supplement. Altogether, our data suggest that the dietary supplementation with forskolin, homotaurine, spearmint extract and vitamins of the B group supports RGC survival and may offer beneficial effects in glaucoma patients in combination with the currently used IOP-lowering therapy. [ABSTRACT FROM AUTHOR]

João Heitor Marques,1 João Coelho,1 Maria João Menéres,1,2 João Melo Beirão1,2 1Serviço de Oftalmologia, Centro Hospitalar Universitário do Porto, Porto, Portugal; 2Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, PortugalCorrespondence: João Heitor Marques, Serviço de Oftalmologia, Centro Hospitalar Universitário do Porto, Largo do Prof. Abel Salazar, Porto, Portugal, Tel +351913680736, Email joaoheitormarques@gmail.comAbstract: Retinal angiopathy associated with hereditary transthyretin amyloidosis (ATTRv), if untreated, may lead to irreversible vision loss. Our purpose was to systematically review the clinical and imaging features of retinal angiopathy associated with ATTRv and assemble a monitoring approach for these patients. All types of original research studies reporting clinical and imaging findings on retinal angiopathy associated with ATTRv were included. The most common clinical findings were tortuous retinal vessels, microaneurysms, retinal hemorrhages, sheathing of retinal vessels, whitish amyloid deposits along retinal arteries, obliteration of retinal vessels, vitreous hemorrhage, retinal and iris neovascularization. The most relevant imaging findings were hyperautofluorescence of perivessel amyloid deposits; delayed arterial filling, vascular leakage, and retinal ischemia on fluorescein angiography; late hypercyanescence along the choroidal arteries on indocyanine green angiography; perivascular hyperreflective material, needle-shaped deposits on the retinal surface and macular edema on optical coherence tomography (OCT) and attenuated retinal vascular network on OCT-angiography. ATTRv patients should be strictly followed to detect and treat retinal angiopathy, avoiding complications. Both panretinal photocoagulation and intravitreal anti-vascular endothelial growth factor have been used to treat retinal angiopathy in ATTRv. In an individual that presents with retinal angiopathy of unknown etiology, ATTRv should be considered as in the differential diagnosis, even out of the initial core countries. The prognostic value of subclinical findings, namely in OCT-A, is not yet established.Keywords: amyloidosis, transthyretin amyloidosis, retinal angiopathy, fluorescein angiography, retinal ischemia

An ophthalmology consultation was requested for a 29-year-old woman complaining of visual field defects. The patient had presented to the emergency department with cough and high fever one day earlier. Chest computed tomography demonstrated pneumonia and two severe acute respiratory syndrome coronavirus 2 polymerase chain reaction tests were positive. The patient had undergone renal transplantation 11 years ago due to glomerulonephritis. Best-corrected visual acuity (BCVA) was 20/40 in the right eye and 20/30 in the left eye. Fluorescein angiography showed macular hypoperfusion, and optical coherence tomography (OCT) showed hyperreflectivity in the inner nuclear, outer plexiform, and outer nuclear layers, as well as discontinuity of the ellipsoid zone. Perimetry confirmed bilateral central scotoma. Levels of D-dimer and fibrinogen were 0.86 g/mL and 435.6 g/mL, respectively. The patient was diagnosed as having concurrent acute macular neuroretinopathy and paracentral acute middle maculopathy and was given low-molecular-weight heparin treatment for one month. Her BCVA improved to 20/20 in both eyes, and regression was observed in the retinal findings, hyperreflectivity and ellipsoid zone disruption on OCT, and scotoma in perimetry. Inflammation, thrombosis, and glial involvement may play a role in the pathogenesis of retinal microvascular impairment in COVID-19. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic retinopathy is a vascular condition of the retina that develops as a result of diabetes mellitus (DM). This study aimed to compare intravitreal bevacizumab, panretinal photocoagulation or a combination of both in proliferative diabetic retinopathy. Method: In this prospective, randomized interventional study, 180 patients with PDR were enrolled and divided into three equal groups, i.e., Group A-patients treated with laser alone and Group Bpatients treated with Anti-VEGF alone and Group C-patients treated with Anti-VEGF and laser. A detailed history, clinical and demographical data of all the patients were recorded and compared. The examination was done, including visual acuity assessment with Snellen's chart, Slit-lamp biomicroscopic examination, intraocular pressure and pupillary assessment for optic nerve dysfunction. Results: The mean age of group-A, B and C, 57.13±6.88, 55.62±5.97 and 54.86±4.98 respectively were comparable. At the same time, most of the patients were between the age group of 58-66years [25(41.67%)]. Majority of the patients were male in all three groups. A significant difference was observed in mean FBS and duration of diabetes. In group-A and C, most patients affected eye was left [35(58.33%)] and [34(56.67)], respectively, while in group B right eye was affected [33(55.00%)]. The mean VA Log MAR was found to be significant among the three groups. Mean SNELLENS and IOP were insignificant among the groups. At first, follow up the mean VA Log MAR, SNELLENS, FFA and OCT were found significant among the groups. At second follow-up, the mean VA LOG MAR was significant. Intragroup analysis between treatment of the eye was found insignificant, while the rest of the parameters and characteristics were found significant. Conclusion: The present study suggests that the Anti-VEGF + PRP were the best treatment regime, followed by Anti VEGF and the least effective one was PRP. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the study was to characterize the 2-year progression of risk phenotypes of nonproliferative diabetic retinopathy (NPDR) in type 2 diabetes (T2D) phenotype C, or ischemic phenotype, identified by decreased skeletonized retinal vessel density (VD), ≥2 SD over normal values, and phenotype B, or edema phenotype, identified by increased retinal thickness, i.e., subclinical macular edema, and no significant decrease in VD. Methods: A prospective longitudinal cohort study (CORDIS, NCT03696810) was conducted with 4 visits (baseline, 6 months, 1 year, and 2 years). Ophthalmological examinations included best-corrected visual acuity, color fundus photography (CFP), and optical coherence tomography (OCT) and OCT angiography. Early Treatment Diabetic Retinopathy Study grading was performed at the baseline and last visits based on 7-field CFP. Results: One hundred and twenty-two eyes from T2D individuals with NPDR fitted in the categories of phenotypes B and C and completed the 2-year follow-up. Sixty-five (53%) of the eyes were classified as phenotype B and 57 (47%) eyes as phenotype C. Neurodegeneration represented by thinning of the ganglion cell layer and inner plexiform layer was present in both phenotypes and showed significant progression over the 2-year period (p < 0.001). In phenotype C, significant progression in the 2-year period was identified in decreased skeletonized VD (p = 0.01), whereas in phenotype B microvascular changes involved preferentially decrease in perfusion density (PD, p = 0.012). Phenotype B with changes in VD and PD (flow) and preferential involvement of the deep capillary plexus (p < 0.001) is associated with development of center-involved macular edema. Discussion: In the 2-year period of follow-up, both phenotypes B and C showed progression in retinal neurodegeneration, with changes at the microvascular level characterized by decreases in PD in phenotype B and decreases in VD in phenotype C. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to evaluate changes in retinal capillary nonperfusion areas (RCNPA) and the retinal capillary vessel density (RCVD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) using widefield optical coherence tomography angiography (WFOCTA) in patients with diabetic retinopathy (DR) and diabetic macular edema (DME) treated with intravitreal ranibizumab injection (IRI). Materials and Methods: Twenty-four eyes of 24 patients with DR and DME candidates to a loading dose of IRI were enrolled. All patients underwent WFOCTA with the PLEX Elite 9000 device with 15 × 9 mm scans centered on the foveal center at baseline (T0) and 1 month after each intravitreal injection at 30 days (T1), 60 days (T2), and 90 days (T3). In all patients, the variation of RCNPA and the RCVD of the SCP and DCP were calculated using automatic software written in MATLAB (MathWorks, Natick, MA, USA). Results: The SCP showed a significant longitudinal variation of RCNPA (p = 0.04). Post hoc analysis revealed a statistically significant reduction of RCNPA at T1 (p = 0.04) and a nonsignificant reduction at T2 (p = 0.18) and T3 (p = 0.96). The DCP showed longitudinal changes in the RCNPA that tended to statistical significance (p = 0.09). Post hoc analysis revealed a trend toward a statistically significant reduction of RCNPA at T3 (p = 0.09) not statistically significant at T1 (p = 0.17) and T2 (p = 0.75). The RCVD of SCP and DCP showed no significant changes at any of the time points. Conclusions: WFOCTA showed a decrease in RCNPA after IRI, probably related to the reperfusion of retinal capillaries. [ABSTRACT FROM AUTHOR]

Optic nerve avulsion injury can cause retinal ischemia because of interruption of retinal blood flow as a result of nerve shearing injury. Multimodal imaging can reveal focal retinal injury and aid in proper diagnosis and follow-up. Purpose: Traumatic optic neuropathy can have varying presentations. Blunt focal trauma can lead to optic nerve avulsion with underlying retinal findings. A case of partial optic nerve avulsion after finger poke injury leading to focal retinal ischemia is reported. Methods: Visual acuity, fundus photography with fluorescein angiography, and spectral-domain optical coherence tomography were performed to document the findings in a 16-year-old man who presented after a finger poke injury to the left orbit during a water polo match. Results: On initial presentation, examination revealed decreased visual acuity with a fixed left pupil and afferent pupillary defect by reverse. On slit-lamp examination of the left eye, a hyphema was present. Dilated fundus examination revealed layering vitreous hemorrhage over the posterior pole and an avulsed vitreous base. On follow-up, a gap temporal to the optic nerve head consistent with a partial optic nerve avulsion was noted once the vitreous hemorrhage cleared. Multimodal imaging revealed retinal ischemia temporal to the disc on fluorescein angiography with corresponding changes in the inner retinal layers and retinal nerve fiber layer using spectral-domain optical coherence tomography. Conclusion: Clinicians should have a high suspicion for optic nerve avulsion if a patient presents with new vitreous hemorrhage and afferent pupillary defect after a finger-poke injury. Optic nerve avulsion injury can cause retinal ischemia, likely because of interruption of retinal blood flow as a result of nerve shearing injury. Multimodal imaging can reveal focal retinal injury and aid in proper diagnosis and follow-up. [ABSTRACT FROM AUTHOR]

Background and objectives: EG-Mirotin (active ingredient EGT022) targets nonproliferative diabetic retinopathy (NPDR), the early stage of retinopathy. EG-Mirotin reverses capillary damage before NPDR progresses to an irreversible stage. EG-Mirotin safety and efficacy were investigated in patients with type 1 or type 2 diabetes mellitus and moderate to severe NPDR. Methods: In this open-label, single-arm, single-center, exploratory phase II study, 10 patients (20 eyes) received EG-Mirotin once a day (3 mg/1.5 mL sterile saline) for 5 days and were evaluated for ischemic index changes and safety. End of study was approximately 8 ± 1 weeks (57 ± 7 days) after the first drug administration. Results: EG-Mirotin injections were well tolerated, with no dose-limiting adverse events, serious adverse events, or deaths. Four treatment-emergent adverse events (TEAEs) unrelated to the investigational drug were observed in 2 out of 10 participants (20%) who had received the investigational drug. The overall average percent change in ischemic index at each evaluation point compared with baseline was statistically significant (Greenhouse–Geisser F = 9.456, p = 0.004 for the main effect of time), and a larger change was observed when the baseline ischemic index value was high (Greenhouse–Geisser F = 10.946, p = 0.002 for time × group interaction). Conclusions: The EG-Mirotin regimen established in this study was shown to be feasible and safe and was associated with a trend toward potential improvement in diabetes-induced ischemia and retinal capillary leakage. [ABSTRACT FROM AUTHOR]