Effects of repeated low-level red-light therapy on macular retinal thickness and microvascular system in children with myopia.

OBJECTIVE: The objective of the study was to use optical coherence tomography angiography (OCTA) to analyze the effects of repeated low-level red-light (LLLT) therapy on macular retinal thickness and the microvascular system in children with myopia to evaluate the safety of this therapy. METHODS: This prospective study included 40 school-age children with myopia (80 eyes), aged 7-14 years, who received therapy using a LLLT instrument. At baseline and therapy for 1 month, 3 months, 6 months, all children underwent comprehensive ophthalmological examinations, including slit-lamp examination, uncorrected visual acuity, best-corrected visual acuity, spherical equivalent degree, axial length, and OCTA. The vessel densities of the superficial retinal capillary plexus, macular inner retinal thickness, and full-layer retinal thickness were measured. RESULTS: The macular inner retinal thickness increased at 1 month and remained unchanged thereafter, It differed significantly in nine areas at 1, 3, and 6 months compared to the thicknesses before therapy (P < 0.05); however, we observed no significant differences between the different time points (P > 0.05). The macular full-layer retinal thickness increased at 1 month and remained unchanged thereafter; the changes showed significant differences at 1 month and 3 months compared to before therapy, for the inner nasal region (P < 0.05). The other eight areas showed significant differences at 1, 3, and 6 months compared with before therapy (P < 0.05); however, no significant difference was observed between the different time points after therapy (P > 0.05). The vessel density of the superficial retinal capillary plexus did not differ significantly among the four groups (P > 0.05). CONCLUSIONS: LLLT therapy was safe. The school-aged children exhibited macular thickening after LLLT therapy, which had no significant effect on macular microcirculation.

Paracentral acute middle maculopathy in a fasting patient after cataract surgery and its response to hyperbaric oxygen therapy.

INTRODUCTION: Paracentral acute middle maculopathy (PAMM) is a structural optical coherence tomography (OCT) sign secondary to ischemia in the intermediate and deep retinal vascular network, characterized by hyperreflectivity in the inner nuclear layer (INL). AIM: Our objective is to demonstrate PAMM development following uncomplicated cataract surgery, possibly triggered by fasting and dehydration. We also aim to emphasize the potential role of hyperbaric oxygen therapy in treating PAMM. CASE PRESENTATION: A 66-year-old man with a past medical history of Neurofibromatosis type 1 and cardiovascular disease underwent uncomplicated cataract surgery in the left eye. The patient was also fasting due to Ramadan. The patient complained of very low vision during the routine postoperative examination on the third day. His-best-corrected visual acuity (BCVA) was counting fingers at 1 meter. His-anterior and posterior segment examination was unremarkable. In infrared imaging, a large hyporeflective area was observed in the parafoveal region, and structural OCT also showed increased hyperreflectivity in the middle retinal layers corresponding to the junction of INL and outer plexiform layer (OPL) involving the entire INL which suggested PAMM. Following 14 sessions of hyperbaric oxygen therapy, the patient's BCVA increased to 0.9 on the 14th day of diagnosing PAMM. CONCLUSION: To the best of our knowledge, this is the first case representing a patient with  PAMM triggered by fasting and cataract surgery who responded positively to hyperbaric oxygen therapy. However, triggering of PAMM by fasting is entirely unproven and that this observation occurred in a highly complex case with many other possible contributing factors. Also, the triggering of PAMM by some manipulation during surgery is equally unproven.

Akimba Proliferative Diabetic Retinopathy Model: Understanding Molecular Mechanism and Drug Screening for the Progression of Diabetic Retinopathy.

As the prevalence of diabetes has reached epidemic proportions worldwide, diabetic retinopathy incidence is increasing rapidly. An advanced diabetic retinopathy (DR) stage can lead to a sight-threatening form. There is growing evidence showing diabetes causes a range of metabolic changes that subsequently lead to pathological modifications in the retina and retinal blood vessels. To understand the complex mechanism of the pathophysiology of DR, a precise model is not readily available. By crossbreeding the Akita and Kimba strains, a suitable proliferative DR model was acquired. This new Akimba strain manifests marked hyperglycemia and vascular changes, which resemble the early and advanced stage of DR.Here, we describe the breeding method, colony screening for experiments, and imaging techniques widely used to investigate the DR progression in this model. We elaborate step-by-step protocols to set up and perform fundus, fluorescein angiography, optical coherence tomography, and optical coherence tomography-angiogram to study retinal structural changes and vascular abnormalities. In addition, we show a method to label the leukocytes with fluorescence and laser speckle flowgraphy to examine the inflammation in the retina and retinal vessel blood flow speed, respectively. Lastly, we describe electroretinogram to evaluate the functional aspect of the DR transformations.

Time course study of optical coherence tomography angiography in patients with methanol induced optic neuropathy.

INTRODUCTION: In countries where alcoholic beverages are legally prohibited, methanol toxicity usually occurs due to ingesting homemade alcoholic drinks. The initial ophthalmologic symptoms of methanol toxicity typically appear 6-48 h after ingestion, and the severity of symptoms varies widely from mild and painless decreased vision to no-light perception vision. METHODS: This prospective study examines 20 patients with acute methanol poisoning within 10 days of use. Patients underwent ocular examinations, BCVA (Best Corrected Visual Acuity) recording, and OCTA (Optical Coherence Tomography Angiography) of the macula and optic disc. BCVA measurement and imaging were repeated one month and three months after intoxication. RESULTS: There was a statistically significant reduction in superficial parafoveal vascular density (P-value = 0.026), inner retinal thickness (P-value = 0.022), RNFL (Retinal Nerve Fiber Layer) thickness (P-value = 0.031), and an increase in cup to disc ratio (P-value < 0.001), and central visual acuity (P-value = 0.002) in this time course. However, there was no statistically significant difference in FAZ (Foveal Avascular Zone) area (P-value = 0.309), FAZ perimeter (P-value = 0.504), FD-300 (Foveal density, vascular density within a 300 µm wide region of the FAZ) (P-value = 0.541), superficial vascular density (P-value = 0.187), deep foveal vascular density (P-value = 0.889), deep parafoveal vascular density (P-value = 0.830), choroidal flow area (P-value = 0.464), total retinal thickness (P-value = 0.597), outer retinal thickness (P-value = 0.067), optic disc whole image vascular density (P-value = 0.146), vascular density inside the disc (P-value = 0.864), or peripapillary vascular density (P-value = 0.680) at different times. CONCLUSION: Over time, methanol poisoning can cause changes in retinal layers thickness, vasculature, and optic nerve head. The most important changes include cupping of the optic nerve head, reduction in RNFL thickness, and inner retinal thickness.

Clinical identification of optic disk vascular alteration in glaucoma.

Background: Several characteristic vascular changes can be observed in the glaucomatous eyes, including changes in the vessel configuration and caliber, presence of collateral vessel on disk, and disk hemorrhage. Purpose: This video describes characteristic vascular changes in the optic nerve head, which can be observed on clinical examination in the glaucomatous eyes, and useful teaching points to identify the same. Synopsis: In glaucoma, as the optic cup enlarges, the normal pattern and course of retinal vessels on the optic disk are altered and show characteristic changes. Identification of these changes provides a clue to the presence of cupping. Highlights: In this video, the vascular changes and its identification in the glaucomatous disc are described, which would be useful to the residents. Video link: https://youtu.be/2eINumBx33E.

The effect of palm oil-derived tocotrienol-rich fraction in preserving normal retinal vascular diameter in streptozotocin-induced diabetic rats.

PURPOSE: Angiogenesis in diabetic retinopathy (DR) is associated with increased retinal expression of angiopoietin-2 (Ang-2) and protein kinase C (PKC). Tocotrienol-rich fraction (TRF) has been shown to reduce the expression vascular endothelial growth factor (VEGF) in several experimental models. However, its effect against other angiogenic markers such as Ang-2 and PKC in rat model of diabetes remains unknown. Therefore, we investigated the effect of TRF on the retinal vascular changes and Ang-2 and PKC expressions in rats with streptozotocin (STZ)-induced DR. METHODS: Sprague-Dawley rats were divided into normal control rats (N) which received vehicle, and diabetic rats which either received vehicle (DV) or 100 mg/kg of TRF (DT). Diabetes was induced with intraperitoneal injection of STZ (60 mg/kg body weight). Treatments were given orally, once daily, for 12 weeks after confirmation of hyperglycaemia. Fundus photographs were captured at baseline, 6- and 12-week post-STZ injection and average diameter of retinal veins and arteries were measured. At 12-week post-STZ injection, rats were euthanised, and retinae were collected for measurement of Ang-2 and PKC gene and protein expressions. RESULTS: Retinal venous and arterial diameters were significantly greater in DV compared to DT at week 12 post-STZ injection (p < 0.001 and < 0.05, respectively). The vessel diameter measurements in DT were comparable to N and this effect of TRF was associated with significantly lower Ang-2 and PKC gene and protein expressions compared to DV. CONCLUSION: Oral TRF reduces the expression of retinal angiogenic markers and preserves the retinal vascular diameter of rats with STZ-induced DR.

Effect of a Fixed Combination of Curcumin, Artemisia, Bromelain, and Black Pepper Oral Administration on Optical Coherence Tomography Angiography Indices in Patients with Diabetic Macular Edema.

Background: To investigate the effects of a fixed combination of Curcumin (200 mg), Artemisia (80 mg), Bromelain (80 mg), and Black pepper (2 mg) on vascular parameters in mild to moderate diabetic macular edema (DME). Design: Prospective, case-control study. Methods: Fifty-six patients affected by diabetes mellitus type II were enrolled in the study. Twenty-eight patients with DME received 2 tablets/day, before meals of a dietary complementary supplement containing in fixed combination Curcumin (200 mg), Artemisia (80 mg), Bromelain (80 mg), and Black pepper (2 mg) (Intravit®, OFFHEALTH Spa, Firenze, Italy) for 6 months. Twenty-eight age-matched subjects affected by diabetes mellitus type II were given placebo and served as control group. Patients underwent best correct visual acuity (BCVA), swept optical coherence tomography (OCT), and OCT-Angiography (OCTA). OCTA images of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were obtained for each eye. By the end of the follow-up patients were defined responder to the therapy when a decrease of more than 30 µm was registered in central retinal thickness (CRT) measurement, while a poor responder was determined by the absence of reduction or an increase in central retinal thickness at 6 months. We assessed the foveal avascular zone (FAZ) area, vessel density and quantified the number of microaneurysms in each layer. Results: A significant improvement of BCVA and CRT reduction was recorded at 6 months follow-up in the dietary complementary supplementation group compared to control (respectively p = 0.028 and p = 0.0003). VD of the total capillary plexus, microaneurysms count, glycaemia and HbA1c did not vary over the follow-up period between groups. Within the Intravit® group, poor responders tended to show a larger FAZ area, more microaneurysms, and a lower VD in the DCP compared to the good responders group (p < 0.0001). Conclusions: A fixed combination of Curcumin, Artemisia, Bromelain, and Black pepper oral administration may have a positive impact on central retinal thickness, visual acuity, and VD of the DCP in compensated type 2 diabetic patients with mild DME.

Paracentral acute middle maculopathy (PAMM) associated with ulcerative colitis and coexisting hyperhomocysteinemia: A case report.

INTRODUCTION: Paracentral acute middle maculopathy (PAMM) is a tomographic finding of a retinal occlusive vascular disorders with different aetiologies. Despite the well documented triple association among hyper-homocysteine, retinal vein occlusion and PAMM, up to date no reports exist on the development of PAMM in young patients affected by ulcerative colitis (UC). CASE DESCRIPTION: A multimodal imaging study, including fundus photographs, optical coherence tomography (OCT) B-scans, OCT angiography (OCT-A) and fluorescein and indocyanine green angiography, was performed in a 32-years-old male complaining of acute-onset paracentral scotoma in the right eye. Fundus images demonstrated the typical dark gray area of retinal capillary ischemia, corresponding on OCT B-scans to the hyper-reflective plaques in the INL, and consistent with PAMM lesions.The deep capillary plexus (DCP) was normal on OCT-A. Fluorescein angiography revealed a concurrent branch retinal vein preocclusion and showed capillary drop out parafoveally. Patient's anamnesis was negative except for a 15-years history of UC and use of acetylsalicylic acid (ASS). At the time of presentation, UC was quiescent, but new blood tests revealed concomitant high values of homocysteinemia requiring oral vitamin B12 and folate supplementation. Two months later PAMM lesions had disappeared on OCT B-scans and a retinal thinning at the level of the inner nuclear layer (INL) was visible. The DCP on OCT-A remained unchanged without any sign of capillary ischemia. CONCLUSIONS: Although no definitive evidence directly links UC with PAMM, the latter should be suspected in young patients affected by IBD with coexisting hyper-homocysteinemia and unexplained visual symptoms.

Lycium barbarum polysaccharides attenuates high glucose-induced diabetic retinal angiogenesis by rescuing the expression of miR-15a-5p in RF/6A cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Lycium barbarum L., a classical traditional Chinese Medicine, has long been used to treat ocular diseases. Lycium barbarum polysaccharides (LBP) is an effective component of Lycium barbarum L. with a wide range of pharmacological activities. This research aims to investigate the inhibition of high glucose-induced angiogenesis by LBP in RF/6A cells. MATERIALS AND METHODS: A high-glucose-induced angiogenesis model was established using monkey retinal vascular endothelial (RF/6A) cells. Different dosages administration times of LBP and glucose concentrations were tested. Under the optimized conditions, RF/6A cells were treated with LBP for 48 h, followed by another 48-h culture in high glucose (25 mmol/L) medium. The effect and mechanism of LBP were investigated following the treatment. RESULTS: The expression of miR-15a-5p and miR-15a-3p in RF/6A cells decreased significantly after 48 h of 25 or 50 mmol/L high glucose treatment. The expression of miR-15a-5p was higher than that of miR-15a-3p. Mimic-miR-15a-5p or 600 mg/L LBP could increase the apoptosis of cells and the total length of vascular branches. The expression of VEGFA, VEGFR2, and ANG2 proteins was reduced, while the expression of ANG1 protein was elevated. Expression of ASM mRNA and protein was also inhibited. CONCLUSIONS: LBP attenuates diabetic retinal angiogenesis by rescuing the expression of miR-15a-5p in RF/6A cells.

HDC-Net: A hierarchical dilation convolutional network for retinal vessel segmentation.

The cardinal symptoms of some ophthalmic diseases observed through exceptional retinal blood vessels, such as retinal vein occlusion, diabetic retinopathy, etc. The advanced deep learning models used to obtain morphological and structural information of blood vessels automatically are conducive to the early treatment and initiative prevention of ophthalmic diseases. In our work, we propose a hierarchical dilation convolutional network (HDC-Net) to extract retinal vessels in a pixel-to-pixel manner. It utilizes the hierarchical dilation convolution (HDC) module to capture the fragile retinal blood vessels usually neglected by other methods. An improved residual dual efficient channel attention (RDECA) module can infer more delicate channel information to reinforce the discriminative capability of the model. The structured Dropblock can help our HDC-Net model to solve the network overfitting effectively. From a holistic perspective, the segmentation results obtained by HDC-Net are superior to other deep learning methods on three acknowledged datasets (DRIVE, CHASE-DB1, STARE), the sensitivity, specificity, accuracy, f1-score and AUC score are {0.8252, 0.9829, 0.9692, 0.8239, 0.9871}, {0.8227, 0.9853, 0.9745, 0.8113, 0.9884}, and {0.8369, 0.9866, 0.9751, 0.8385, 0.9913}, respectively. It surpasses most other advanced retinal vessel segmentation models. Qualitative and quantitative analysis demonstrates that HDC-Net can fulfill the task of retinal vessel segmentation efficiently and accurately.

Effects of Ocufolin on retinal microvasculature in patients with mild non-proliferative diabetic retinopathy carrying polymorphisms of the MTHFR gene.

INTRODUCTION: To evaluate effects of Ocufolin on retinal microvasculature in mild non-proliferative diabetic retinopathy patients who carried methylenetetrahydrofolate reductase (MTHFR) polymorphisms (DR+MTHFRP). RESEARCH DESIGN AND METHODS: This is a prospective cohort study. Eight DR+MTHFRP (administrated Ocufolin for 6 months) and 15 normal controls (NCs) were recruited. MTHFR polymorphisms were subtyped as normal, C677T, or A1298C. Best-corrected visual acuity (BCVA) was evaluated. Retinal vessel density (VD) and microstructure were evaluated by optical coherence tomography angiography. RESULTS: BCVA and vascular indices of DR+MTHFRP at baseline were worse than those of NC and improved. Compared with baseline, DR+MTHFRP had significantly improved BCVA during follow-up period (p<0.05). VD of superficial vascular plexus was increased at 4 months (p=0.012), while VD of retinal vascular network did not change (p>0.05). Carriers of A1298C and C677T showed statistically significant increase in VD at all layers by 6 months, while carriers of C677T alone showed no significant change and carriers of A1298C alone showed decreased density from 4 months to 6 months. Microstructure did not change during the follow-up period. CONCLUSION: A 6-month intake of Ocufolin is capable of reversing structural changes of microangiopathy in mild non-proliferative DR+MTHFRP. This suggests a novel way to address these impairments prior to catastrophic vision loss.

Estimation of stroke severity with National Institutes of Health Stroke Scale grading and retinal features: A cross-sectional study.

ABSTRACT: To estimate National Institutes of Health Stroke Scale (NIHSS) grading of stroke patients with retinal characteristics.A cross-sectional study was conducted in Shenzhen Traditional Chinese Medicine Hospital. Baseline information and retinal photos were collected within 2 weeks of admission. An NIHSS score was measured for each patient by trained doctors. Patients were classified into 0 to 4 score group and 5 to 42 score group for analysis. Three multivariate logistic models, with traditional clinical characteristics alone, with retinal characteristics alone, and with both, were built.For clinical characteristics, hypertension duration is statistically significantly associated with higher NIHSS score (P = .014). Elevated total homocysteine levels had an OR of 0.456 (P = .029). For retinal characteristics, the fractal dimension of the arteriolar network had an OR of 0.245 (P < .001) for the left eyes, and an OR of 0.417 (P = .009) for right eyes. The bifurcation coefficient of the arteriole of the left eyes had an OR of 2.931 (95% CI 1.573-5.46, P = .001), the nipping of the right eyes had an OR of 0.092 (P = .003) showed statistical significance in the model.The area under receiver-operating characteristic curve increased from 0.673, based on the model with clinical characteristics alone, to 0.896 for the model with retinal characteristics alone and increased to 0.931 for the model with both clinical and retinal characteristics combined.Retinal characteristics provided more information than clinical characteristics in estimating NIHSS grading and can provide us with an objective method for stroke severity estimation.

Serum and Macular Carotenoids in Relation to Retinal Vessel Caliber Fifteen Years Later, in the Second Carotenoids in Age-Related Eye Disease Study.

Purpose: We investigated whether dietary carotenoids lutein and zeaxanthin (L/Z) in the serum and macula were associated with central retinal arteriole and venule calibers in a follow-up ancillary study among older women in the Women's Health Initiative. Methods: Among 390 women who participated in Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2) (2016-2019), we investigated associations between serum L/Z at Women's Health Initiative baseline (1994-1998), and macular pigment optical density (MPOD) at CAREDS baseline (2001-2004), with central retinal vessel caliber in CAREDS2. MPOD was measured using heterochromatic flicker photometry (0.5° from the foveal center) in CAREDS baseline and CAREDS2. Vessel calibers were measured from fundus photographs (CAREDS2). We also explored associations in women with stable MPOD (±0.10 optical density units) over 15 years (n = 106), given the long-term increases in MPOD related to diet patterns and supplement use. Associations were investigated using linear modeling. Results: In the full sample (n = 390), higher serum L/Z (tertile 3 vs. 1) was positively associated with arteriole caliber (mean ± SE, 145.0 ± 1.4 µm vs. 140.8 ± 1.4 µm; P = 0.05) and venule caliber (214.6 ± 2.2 µm vs. 207.5 ± 2.2 µm; P = 0.03). MPOD was also associated with wider vessel calibers (tertile 3 vs. 1), but the trend was only statistically significant for venules (144.4 ± 1.4 µm vs. 141.1 ± 1.4 µm [P = 0.12] and 213.3 ± 2.1 µm vs. 206.0 ± 2.1 µm [P = 0.02], respectively.) Most associations were strengthened in women with stable MPOD over 15 years, including between MPOD and arteriole caliber (149.8 ± 2.6 µm vs.135.8 ± 3.0 µm; P = 0.001). Conclusions: Higher L/Z status in serum and retina was associated with larger central retinal vessel calibers. Prospective studies and clinical trials are needed to elucidate whether L/Z supplementation prevents vision loss through increasing blood flow.

Role of Choline in Ocular Diseases.

Choline is essential for maintaining the structure and function of cells in humans. Choline plays an important role in eye health and disease. It is a precursor of acetylcholine, a neurotransmitter of the parasympathetic nervous system, and it is involved in the production and secretion of tears by the lacrimal glands. It also contributes to the stability of the cells and tears on the ocular surface and is involved in retinal development and differentiation. Choline deficiency is associated with retinal hemorrhage, glaucoma, and dry eye syndrome. Choline supplementation may be effective for treating these diseases.

Amelioration of diabetic retinopathy in db/db mice by treatment with different proportional three active ingredients from Tibetan medicine Berberis dictyophylla F.

ETHNOPHARMACOLOGICAL RELEVANCE: Berberis dictyophylla F., a famous Tibetan medicine, has been used to prevent and treat diabetic retinopathy (DR) for thousands of years in clinic. However, its underlying mechanisms remain unclear. AIM OF THE STUDY: The present study was designed to probe the synergistic protection and involved mechanisms of berberine, magnoflorine and berbamine from Berberis dictyophylla F. on the spontaneous retinal damage of db/db mice. MATERIALS AND METHODS: The 14-week spontaneous model of DR in db/db mice were randomly divided into eight groups: model group, calcium dobesilate (CaDob, 0.23 g/kg) group and groups 1-6 (different proportional three active ingredients from Berberis dictyophylla F.). All mice were intragastrically administrated for a continuous 12 weeks. Body weight and fasting blood glucose (FBG) were recorded and measured. Hematoxylin-eosin and periodic acid-Schiff (PAS) stainings were employed to evaluate the pathological changes and abnormal angiogenesis of the retina. ELISA was performed to assess the levels of IL-6, HIF-1α and VEGF in the serum. Immunofluorescent staining was applied to detect the protein levels of CD31, VEGF, p-p38, p-JNK, p-ERK and NF-κB in retina. In addition, mRNA expression levels of VEGF, Bax and Bcl-2 in the retina were monitored by qRT-PCR analysis. RESULTS: Treatment with different proportional three active ingredients exerted no significant effect on the weight, but decreased the FBG, increased the number of retinal ganglionic cells and restored internal limiting membrane. The results of PAS staining demonstrated that the drug treatment decreased the ratio of endothelial cells to pericytes while thinned the basal membrane of retinal vessels. Moreover, these different proportional active ingredients can markedly downregulate the protein levels of retinal CD31 and VEGF, and serum HIF-1α and VEGF. The gene expression of retinal VEGF was also suppressed. The levels of retinal p-p38, p-JNK and p-ERK proteins were decreased by drug treatment. Finally, drug treatment reversed the proinflammatory factors of retinal NF-κB and serum IL-6, and proapoptotic Bax gene expression, while increased antiapoptotic Bcl-2 gene expression. CONCLUSIONS: These results indicated that DR in db/db mice can be ameliorated by treatment with different proportional three active ingredients from Berberis dictyophylla F. The potential vascular protection mechanisms may be involved in inhibiting the phosphorylation of the MAPK signaling pathway, thus decreasing inflammatory and apoptotic events.

Coumestrol mitigates retinal cell inflammation, apoptosis, and oxidative stress in a rat model of diabetic retinopathy via activation of SIRT1.

Diabetes-induced oxidative stress is vital in initiating neuronal damage in the diabetic retina, leading to diabetic retinopathy (DR). This study investigates the possible effects of coumestrol (CMS) on streptozotocin (STZ)-induced DR. First, we established a rat model of DR by STZ injection and a cell model involving high-glucose (HG) exposure of human retinal microvascular endothelial cells (hRMECs). We characterized the expression patterns of oxidative stress indicators, pro-inflammatory cytokines, and pro-apoptotic proteins in hRMECs. Polymerase chain reaction showed sirtuin 1 (SIRT1) to be poorly expressed in the retinal tissues of STZ-treated rats and HG-exposed hRMECs, but its expression was upregulated upon treatment with CMS treatment. Furthermore, CMS treatment attenuated the STZ-induced pathologies such as oxidative stress, inflammation, and cell apoptosis. Consistent with the in vivo results, CMS activated the expression of SIRT1, thereby inhibiting oxidative stress, inflammation, and apoptosis of HG-treated hRMECs. From these findings, we concluded that CMS ameliorated DR by inhibiting inflammation, apoptosis and oxidative stress through activation of SIRT1.

A Non-immunogenic Bivalent d-Protein Potently Inhibits Retinal Vascularization and Tumor Growth.

We report a general approach to engineering multivalent d-proteins with antibody-like activities in vivo. Mirror-image phage display and structure-guided design were utilized to create a d-protein that uses receptor mimicry to antagonize vascular endothelial growth factor A (VEGF-A). Selections against the d-protein form of VEGF-A using phage-displayed libraries of two different domain scaffolds yielded two proteins that bound distinct receptor interaction sites on VEGF-A. X-ray crystal structures of the d-protein/VEGF-A complexes were used to guide affinity maturation and to construct a heterodimeric d-protein VEGF-A antagonist with picomolar activity. The d-protein VEGF-A antagonist prevented vascular leakage in a rabbit eye model of wet age-related macular degeneration and slowed tumor growth in the MC38 syngeneic mouse tumor model with efficacies comparable to those of approved antibody drugs, and in contrast with antibodies, the d-protein was non-immunogenic during treatment and following subcutaneous immunizations.

Ginkgo Biloba affects microvascular morphology: a prospective optical coherence tomography angiography pilot study.

PURPOSE: To analyze the vascular morphology changes after consumption of Ginkgo biloba in healthy volunteers by optical coherence tomography angiography (OCTA). METHODS: Sixty healthy volunteers without systemic and ocular disease were included in this prospective pilot study. After receiving the informed consent of the volunteers, Ginkgo biloba extract (120 mg oral capsule) was administered to sixty volunteers for 4 weeks, once a day in the morning. The main outcome measures were the difference between before and after four-week of consumption in best-corrected visual acuity (BCVA), retinal nerve fiber layer (RNFL) and subfoveal choroidal thickness (sfCT) with optical coherence tomography; whole, foveal, parafoveal and perifoveal regions' superior and deep macular vascular plexus vessel density, foveal avascular zone area (FAZ), FAZ perimeter (PERIM), vessel density in a 300 µm wide region around FAZ (FD-300), choroidal and outer retinal flow area, radial peripapillary capillary (RPC) vascular density of whole, inside the disc, peripapillary and four quadrants with OCTA. RESULTS: The study group consisted of sixty eyes of 32 women and 28 men with a mean age of 20.57 ± 1.16 years. In post-consumption measurements, peripapillary and superior, inferior, temporal quadrant RPC vascular density (%) was statistically significantly higher than pre-consumption measurements (p 0.020, p 0.021, p 0.008 and p 0.014, respectively). No significant difference was observed for BCVA, sfCT, other macular or RPC vascular density and flow area OCTA parameters between measurements. CONCLUSION: Four-week consumption of Ginkgo biloba leads to vascular morphological changes in RPC. Further clinical studies are needed to demonstrate its use and effects/benefits in glaucoma, optic neuropathy and other diseases affecting the optic nerve.

An innovative method for screening and evaluating the degree of diabetic retinopathy and drug treatment based on artificial intelligence algorithms.

Current methods of evaluating the degree of diabetic retinopathy are highly subjective and have no quantitative standard. To objectively evaluate the slight changes in tissue structure during the early stage of retinal diseases, a subjective interpretation and qualitative analysis of the pathological sections of retinal HE in diabetic animals is required for screening and evaluating the degree of diabetic retinopathy and drug efficacy. To develop an innovative method for screening and evaluating the degree of diabetic retinopathy and drug treatment based on artificial intelligence algorithms. Based on the change law of the early nerve fiber layer and the ganglion cells, we get disparate characteristics of the microscopic image of diabetes animal retina HE slices. Using image recognition and deep learning methods on these HE slices, we can identify the changes in the ganglion cells and nerve fiber layer for diagnosing early retinopathy and evaluated the therapeutic effect of the potential drugs. We conduct quantitative calculation per unit length of the nerve fiber layer and total area of the nerve fiber layer to identify biology significance of edema. Additionally, we also perform quantitative calculation with the number of unit area ganglion cells to identify the section in biology cell hyperplasia. Finally, we get the significance of quantitative calculation on the unit cell area to identify ganglion cell shriveling in biology. In addition to the evaluation of the disease degree and changes, we also obtained retinal HE sections after different drug interventions and evaluated the therapeutic effect of the drugs. This study presents a novel quantitative method for screening and evaluating of diabetic retinopathy and drug efficacy.

A pilot study to assess the effect of a three-month vitamin supplementation containing L-methylfolate on systemic homocysteine plasma concentrations and retinal blood flow in patients with diabetes.

Purpose: The aim of the present study was to investigate the effect of a three-month dietary supplementation with a methylfolate formulation on homocysteine plasma concentrations and ocular blood flow parameters in patients with diabetes. Methods: Twenty-four patients with diabetes received a dietary supplement (Oculofolin, Aprofol AG, Switzerland) containing 900 µg L­methylfolate (levomefolate calcium or [6S]-5-methyltetrahydrofolic acid, calcium salt), methylcobalamin, and other ingredients for three consecutive months. The patients' plasma homocysteine concentration and retinal blood flow were assessed at baseline and after three months of folate intake. Retinal blood flow was measured using a custom-built dual-beam Doppler optical coherence tomography (OCT) system. In addition, flicker-induced retinal vasodilatation was assessed by means of a commercially available dynamic vessel analyzer (IMEDOS, Jena, Germany). Results: Supplementation was well tolerated by all patients. After three months, plasma homocysteine concentration significantly decreased from 14.2 ± 9.3 to 9.6 ± 6.6 µmol/L (p < 0.001). In addition, a tendency toward an increased total retinal blood flow from 36.8 ± 12.9 to 39.2 ± 10.8 µl/min was observed, but this effect did not reach the level of significance (p = 0.11). Supplementation had no effect on retinal vessel diameter or flicker-induced vasodilatation. Conclusions: The present data show that a three-month intake of a dietary supplement containing methylfolate can significantly reduce blood homocysteine levels in patients with diabetes. This is of importance because higher homocysteine plasma levels have been found to be associated with an increased risk of vascular associated systemic diseases and eye diseases. Whether systemic methylfolate supplementation affects retinal perfusion must be studied in a larger population.