Defining reference values of arterioles in healthy individuals for studies with adaptive optics imaging.

Purpose: To investigate age-dependent wall to lumen ratio (WLR) reference values for healthy individuals in adaptive optics imaging (AO). WLR serves as an objective, dimensionless parameter for the evaluation of structural changes in vessels caused by conditions like arterial hypertension, diabetes or vascular stenosis. Methods: 50 right eyes of healthy individuals were examined by adaptive optics imaging. The central big arterioles and smaller arterial branches at least one disc diameter away from the optic disc, approximately above or below the macula were measured by the manufacturer's software. The wall-lumen-ratio (WLR), the wall cross-sectional area (WCSA) and lumen diameter (LD) were assessed. Subsequent data analysis was performed with a focus on variables including age, gender and blood pressure. Results: Normative values for WLR, WCSA and LD in 5 different age groups could be established. However, no significant differences between the age groups were found. Intra-subject comparisons revealed significantly higher WLRs on peripheral branches when compared to central arterioles. WLR showed in this normotensive cohort no relevant correlation with the systolic, diastolic and mean blood pressure. Gender and intraocular pressure had no influence on the vascular parameters. Conclusion: AO is capable of examining vascular alterations in arterioles at an almost microscopic level. Age did not seem to alter WLR, normotensive blood pressure parameters showed also no significant impact. AO-based vessel analysis may provide clinically useful biomarkers for cardiovascular health and should be tested in future studies.

3DVascNet: An Automated Software for Segmentation and Quantification of Mouse Vascular Networks in 3D.

BACKGROUND: Analysis of vascular networks is an essential step to unravel the mechanisms regulating the physiological and pathological organization of blood vessels. So far, most of the analyses are performed using 2-dimensional projections of 3-dimensional (3D) networks, a strategy that has several obvious shortcomings. For instance, it does not capture the true geometry of the vasculature and generates artifacts on vessel connectivity. These limitations are accepted in the field because manual analysis of 3D vascular networks is a laborious and complex process that is often prohibitive for large volumes. METHODS: To overcome these issues, we developed 3DVascNet, a deep learning-based software for automated segmentation and quantification of 3D retinal vascular networks. 3DVascNet performs segmentation based on a deep learning model, and it quantifies vascular morphometric parameters such as vessel density, branch length, vessel radius, and branching point density. We tested the performance of 3DVascNet using a large data set of 3D microscopy images of mouse retinal blood vessels. RESULTS: We demonstrated that 3DVascNet efficiently segments vascular networks in 3D and that vascular morphometric parameters capture phenotypes detected by using manual segmentation and quantification in 2 dimension. In addition, we showed that, despite being trained on retinal images, 3DVascNet has high generalization capability and successfully segments images originating from other data sets and organs. CONCLUSIONS: Overall, we present 3DVascNet, a freely available software that includes a user-friendly graphical interface for researchers with no programming experience, which will greatly facilitate the ability to study vascular networks in 3D in health and disease. Moreover, the source code of 3DVascNet is publicly available, thus it can be easily extended for the analysis of other 3D vascular networks by other users.

[Vasculitis of the retina : Clinical aspects, diagnostics, management and treatment]. / Vaskulitis der Retina : Klinik, Diagnostik, Management und Therapie.

Inflammatory changes in the retinal vessels can be attributed to a wide range of etiologies. These include infections, intraocular and systemic autoimmune processes, general diseases and iatrogenic factors. As the endothelium of the retinal capillaries forms the inner blood-retinal barrier, a disruption of this structure is directly associated with consequences for the fluid electrolyte balance of the retina. Clinical sequelae can include leakage of the retinal vessels and macular edema, which are often functionally threatening and significantly reduce the quality of life of patients. As the eye can be affected as an "index organ", a work-up of the patient by the ophthalmologist is of great importance. In the age of "precision medicine", efforts are being made to gain new insights into the pathogenetic mechanisms of vasculitis through "omics" in order to develop innovative treatment concepts.

Reduced Retinal Blood Vessel Densities Measured by Optical Coherence Tomography Angiography in Keratoconus Patients Are Negatively Correlated with Keratoconus Severity.

Keratoconus (KC) is the most common corneal ectasia. Optical coherence tomography angiography (OCT-A) is a relatively new non-invasive imaging technique that allows the visualization and quantification of retinal and choriocapillary blood vessels. The aim of this study is to assess retinal and choriocapillary vessel density (VD) differences between KC patients and healthy controls and to investigate correlations between VD and KC severity. Fifty-two eyes were included in this exploratory study: twenty-six eyes from 26 KC patients and twenty-six eyes from 26 age- and gender-matched healthy controls. All patients underwent Scheimpflug corneal topography with Pentacam, axis lengths measurement and optical coherence tomography angiography (OCT-A). The thinnest spot in corneal pachymetry, maximum K (Kmax) and KC severity indices from the Belin/Ambrósio enhanced ectasia display (BAD) were also assessed. There was a distinct reduction particularly in the retinal VD of the superficial capillary plexus (SCP). Correlation analyses showed strong and moderate negative correlations between the VD in the macular SCP and BAD KC scores and between the SCP VD and Kmax. There was no difference in retinal thickness between the KC and healthy controls. With this study, further evidence for altered VD measurements by OCT-A in KC patients is given. For the first time, we demonstrated negative correlations between BAD KC scores and retinal blood vessel alterations. A major limitation of the study is the relatively small sample size. Since an artefactual reduction of the quantitative OCT-A measurements due to irregular corneal topography in KC must be assumed, it remains to be investigated whether there are also actual changes in the retinal microcirculation in KC.

Three-Year Follow-Up Study Investigating Changes in Retinal Vascular Morphology and the Relationship with Diabetic Retinopathy in Children with Type 1 Diabetes Mellitus.

INTRODUCTION: This study aimed to investigate changes in retinal microvascular morphology and associated factors, and their relationship with diabetic retinopathy (DR) in children with type 1 diabetes mellitus (T1DM). METHODS: Thirty-eight children enrolled in this 3-year follow-up study underwent complete ophthalmic examinations including fundus photography. Retinal vascular parameters were measured automatically and compared between baseline and follow-up. Multiple linear regression was used to investigate factors affecting changes in vascular parameters. Binary logistic regression was used to analyze the relationship between retinal microvascular morphology and DR. RESULTS: The caliber of all retinal vessels (within 1-1.5 papillary diameter [PD] from the center of the optic disc, p = 0.030; 1.5-2 PD, p = 0.003), arterioles, and venules (1.5-2 PD, p = 0.001) was narrower in nearly all regions in the follow-up group compared with the baseline group. Vascular tortuosity increased in the central part of the retina and decreased in the periphery. The density (1-1.5 PD, p = 0.030) and fractal dimension (p = 0.037) of retinal vessels were increased at the end of the follow-up compared with baseline. Retinal vascular caliber was independently correlated with DR (odds ratio 0.793 [95% confidence interval 0.633-0.993]; p = 0.044). CONCLUSION: Retinal microvascular morphology in children with T1DM varied with the disease course. Narrower retinal vessels may be an independent risk factor for DR. Results of this study emphasized the importance of regular follow-up of fundus vascular morphology for the detection of early DR in children with T1DM.

A Review of Current Literature on Central Retinal Artery Occlusion: Its Pathogenesis, Clinical Management, and Treatment.

The ocular analogue of a cerebral stroke is central retinal artery occlusion (CRAO), a medical emergency concerning the eyes. Most patients experience substantial acute vision loss with a visual acuity of 20/400 or worse, resulting in decreased quality of life (QoL) and decreased functional ability. An impending cerebral stroke and ischemic heart disease are also more likely. The four distinct clinical entities that make up CRAO are non-arteritic CRAO, transitory non-arteritic CRAO, non-arteritic CRAO with cilioretinal artery sparing, and arteritic CRAO. Depending on the CRAO type, clinical traits, visual results, and treatment all vary greatly. Contrary to current belief, there is a spontaneous improvement in the optical field and vision, mainly in the first week. The likelihood of instinctive development in optical acuity in the first seven days varies greatly. The pathogenesis, epidemiology, and medical features of CRAO will be described in this review, along with present and potential management future options.

Andrographis Paniculata (Burm. F.) Flavonoid Compound and Prevention of Diabetic Retinopathy.

Purpose: To explore the effect of the flavonoid compounds of Andrographis paniculata by evaluating the glycemic profile, oxidative process, and inflammatory values in rats with diabetic retinopathy (DR). Methods: An extract of A. paniculata was macerated with ethanol which yielded flavonoid compounds. Streptozotocin was utilized to induce diabetes mellitus in male Wistar rats. Vucetic's methods were used to evaluate the retinal vessel diameters. Antioxidant parameters and inflammatory cytokines were assessed in retinal tissue. Results: A funduscopic examination revealed some alterations in the retinal veins. In comparison to the DR group with no treatment, the diameter of the retinal vessels in the DR group that was treated with the flavonoid component of the A. paniculata extract (FAP) at doses of 20 and 40 mg/kg body weight (BW) was significantly smaller (P <0.05). The DR treatment groups administered with FAP at doses of 20 and 40 mg/kg BW had a greater ability to reduce TNF-alpha and VEGF levels as compared to the DR rats without treatment (P < 0.05), Glutathione, superoxide dismutase (SOD), and catalase levels were increased after receiving FAP at doses of 20 and 40 mg/kg BW (P < 0.05). Conclusion: Administration of doses of 20 and 40 mg/kg BW of the A. paniculata's flavonoid compoundsimproved DR in rats via retinal vessel diameter reduction, TNF-α and VEGF level reduction, and increasing antioxidants, SOD, catalase, and glutathione.

Remnant cholesterol is correlated with retinal vascular morphology and diabetic retinopathy in type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: The association between remnant cholesterol (RC) and diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) remains unclear. Morphological changes in retinal vessels have been reported to predict vascular complications of diabetes, including DR. METHODS: This cross-sectional study included 6535 individuals with T2DM. The RC value was calculated using the recognized formula. The retinal vascular parameters were measured using fundus photography. The independent relationship between RC and DR was analyzed using binary logistic regression models. Multiple linear regression and subgroup analyses were employed to investigate the link between RC and vascular parameters, including the retinal arteriolar diameter (CRAE), venular diameter (CRVE), and fractal dimension (Df). Mediation analysis was performed to assess whether the vascular morphology could explain the association between RC and DR. RESULTS: RC was independently associated with DR in patients with a longer duration of T2DM (> 7 years). Patients with the highest quartile RC levels had larger CRAE (5.559 [4.093, 7.025] µm), CRVE (7.620 [5.298, 9.941] µm) and Df (0.013 [0.009, 0.017]) compared with patients with the lowest quartile RC levels. Results were robust across different subgroups. The association between RC and DR was mediated by CRVE (0.020 ± 0.005; 95% confidence interval: 0.012-0.032). CONCLUSIONS: RC may be a risk factor for DR among those who have had T2DM for a longer period of time. Higher RC levels were correlated with wider retinal arterioles and venules as well as higher Df, and it may contribute to DR through the dilation of retinal venules.

Stiffness Measurement of Retinal Capillaries and Subendothelial Matrix using Atomic Force Microscopy.

Retinal capillary degeneration is a clinical hallmark of the early stages of diabetic retinopathy (DR). Our recent studies have revealed that diabetes-induced increase in retinal capillary stiffness plays a crucial and previously unrecognized causal role in inflammation-mediated degeneration of retinal capillaries. Retinal capillary stiffening results from overexpression of lysyl oxidase, an enzyme that crosslinks and stiffens the subendothelial matrix. Since tackling DR at the early stage is expected to prevent or slow down DR progression and associated vision loss, subendothelial matrix and capillary stiffness represent relevant and novel therapeutic targets for early DR management. Further, direct measurement of retinal capillary stiffness can serve as a crucial preclinical validation step for the development of new imaging techniques for non-invasive assessment of retinal capillary stiffness in animal and human subjects. With this view in mind, we here provide a detailed protocol for the isolation and stiffness measurement of mouse retinal capillaries and retinal subendothelial matrix using atomic force microscopy.

Effect of Intraorbital Mechanical Compression on Retinal Microvascular Perfusion in Quiescent Thyroid-Associated Ophthalmopathy Based on Ocular Biomechanics Measured by Corvis ST.

INTRODUCTION: To analyze the correlation between orbital compliance and retinal vessel density (VD) based on dynamic Scheimpflug analyzer (Corvis ST) and optical coherence tomographic angiography (OCT-A). METHODS: In this prospective observational study, 65 eyes of 44 patients with thyroid-associated ophthalmopathy (TAO) in quiescent stage were included (15 males and 29 females). The whole eye movement (WEM) was detected by Corvis ST. The superficial capillary plexus VD (SCP-VD) and deep capillary plexus VD (DCP-VD) were obtained by scanning the 3 × 3 mm area around the fovea using OCT-A, while the peripapillary vessel density (ppVD) was obtained by scanning the 4.5 × 4.5 mm area around the optic disk. Covariances including biomechanically corrected intraocular pressure (bIOP), axial length, age and gender were adjusted during data analysis. RESULTS: The mean WEM of the participants was 0.235 ± 0.066 mm. The mean SCP-VD and DCP-VD in whole image were 46.20% ± 3.77% and 50.51% ± 3.96%; the mean whole pp-VD was 49.75% ± 2.01%. WEM was positively correlated with SCP-VD (r = 0.327, p = 0.01) and the whole pp-VD (r = 0.394, p < 0.01) after adjusting by gender, axial length (AL), age and bIOP, but it was not significantly correlated with DCP-VD (r = 0.072 p = 0.581). CONCLUSION: Increase in orbital pressure might reduce retinal microvascular perfusion. Our data suggest orbital mechanical compression may be an important cause of retinal VD changes in quiescent patients with TAO.

Retinal Changes in Patients With Covid-19 and Different Expressiveness of Metabolic Changes.

AIMS: To study the relationship between the severity of COVID-induced metabolic changes and the structure and frequency of retinal changes, according to funduscopy data in patients with different clinical courses of COVID-19. MATERIALS AND METHODS: 117 patients with COVID-19 were examined. While examining patients, severity of the course of COVID-19, the expressiveness of changes in the metabolic status were determined; fundus image registration was performed with portable fundus cameras Pictor Plus Fundus Camera and VistaView (Volk Optical). RESULTS: As a result of the research, retinal changes were found in 49 (41.9 %) patients with COVID-19. In 8 (16.3 %) cases, clinically significant (vitreous hemorrhage, prethrombosis of the central retinal vein or branches of the central retinal vein, thrombosis of the central retinal vein or branches of the central retinal vein) COVID-induced retinal and ophthalmological changes were observed, which caused a decrease in visual acuity. In 41 (83.7 %) cases, clinically insignificant changes (cotton wool spots, narrowed retinal vessels, intraretinal and petechial hemorrhages, tortuosity and dilatation of retinal venules) COVID-induced retinal changes were observed. Clinically significant retinal changes occur in patients with a statistically significantly higher level of D-dimer and a greater percentage of lung parenchyma lesion than in the group of patients with clinically insignificant retinal changes (p < 0.05). CONCLUSIONS: The structure of retinal changes in patients with COVID-19 correlates with the severity of the clinical course of the disease and changes in the metabolic status of patients. Metabolic changes are correlated with retinal changes and can be predictive for preventing general vascular complications in COVID-19.

Predictive visual field outcomes after optic chiasm decompressive surgery by retinal vessels parameters using optical coherence tomography angiography.

AIM: To evaluate the predictive value of superficial retinal capillary plexus (SRCP) and radial peripapillary capillary (RPC) for visual field recovery after optic cross decompression and compare them with peripapillary nerve fiber layer (pRNFL) and ganglion cell complex (GCC). METHODS: This prospective longitudinal observational study included patients with chiasmal compression due to sellar region mass scheduled for decompressive surgery. Generalized estimating equations were used to compare retinal vessel density and retinal layer thickness pre- and post-operatively and with healthy controls. Logistic regression models were used to assess the relationship between preoperative GCC, pRNFL, SRCP, and RPC parameters and visual field recovery after surgery. RESULTS: The study included 43 eyes of 24 patients and 48 eyes of 24 healthy controls. Preoperative RPC and SRCP vessel density and pRNFL and GCC thickness were lower than healthy controls and higher than postoperative values. The best predictive GCC and pRNFL models were based on the superior GCC [area under the curve (AUC)=0.866] and the tempo-inferior pRNFL (AUC=0.824), and the best predictive SRCP and RPC models were based on the nasal SRCP (AUC=0.718) and tempo-inferior RPC (AUC=0.825). There was no statistical difference in the predictive value of the superior GCC, tempo-inferior pRNFL, and tempo-inferior RPC (all P>0.05). CONCLUSION: Compression of the optic chiasm by tumors in the saddle area can reduce retinal thickness and blood perfusion. This reduction persists despite the recovery of the visual field after decompression surgery. GCC, pRNFL, and RPC can be used as sensitive predictors of visual field recovery after decompression surgery.

Retinal vessel diameters in intermediate age-related macular degeneration using en face optical coherence tomography.

CLINICAL RELEVANCE: Clinical assessment of age-related macular degeneration (AMD) relies on biomarkers that do not necessarily reflect the contributions of vascular dysfunction. Validation of clinically accessible methods of measuring retinal vascular integrity could provide a more holistic understanding of AMD-related changes to facilitate appropriate care. BACKGROUND: There is conflicting evidence if retinal vessel calibre is significantly altered in the early stages of AMD. This study examined the outer and inner diameters of first order retinal vessels in intermediate AMD eyes using en face optical coherence tomography (OCT). METHODS: Retinal en face (6 × 6 mm) OCT images were examined in a single eye of participants with intermediate AMD (n = 46) versus normal macula (n = 43) for arterioles (all identifiable) and venules (40/46 and 39/43 identifiable). All participants were aged ≥50 years without diabetes mellitus, hypertension, or other systemic vascular disease. RESULTS: Intra- and inter-grader agreement was good-to-excellent for all en face OCT measurements of arteriole and venule diameters (intraclass correlation coefficient = 0.87 to 0.99). Arteriolar outer diameters (82.3 ± 19.8 µm vs 73.8 ± 16.1 µm; p < 0.05) and inner diameters (35.1 ± 8.4 µm vs 31.5 ± 8.1 µm; p < 0.05) were significantly greater in AMD eyes compared to normal eyes. Venular inner diameter was significantly greater (43.1 ± 9.5 µm vs 39.2 ± 10.1 µm; p < 0.05), but outer diameter remained unchanged (p = 0.17) in AMD eyes compared to normal eyes. CONCLUSION: Arteriolar dilation and altered venular inner diameter were observed in intermediate AMD eyes. These results support further investigation of vascular contributions to AMD in the early stages of disease, possibly using the en face OCT imaging modality.

Distinctive Imaging Characteristics of Retinal and Cerebral Vessels between Central and Branch Retinal Vein Occlusion by MRI and AI-Based Image Analyzer.

Retinal vessels have been good predictive and prognostic imaging biomarkers for systemic or eye diseases. Numerous studies have shown that the two retinal vein occlusion entities may correlate with cardiovascular and cerebrovascular events or primary open-angle glaucoma. This study aims to investigate if there is a disparity in the correlations between branch RVO (BRVO) and central RVO (CRVO) with systemic disorders or POAG, thus explaining the pathogenic difference between BRVO and CRVO. This retrospective case-control study enrolled 59 RVO subjects (118 eyes), including 25 CRVO and 34 BRVO subjects, who received routine eye and brain MRI examinations. The geometric characteristics of the caliber of the retinal and cerebral blood vessels and the optic nerve subarachnoid space width (ONSASW) were measured. Multivariable logistic regression analysis showed that ONSASW at 3 mm behind the globe (p = 0.044) and the relative retinal venular calibers (p = 0.031) were independent risk factors for the CRVO-affected eyes group in comparison with the BRVO-affected eyes group after adjusting for age, duration of hypertension, BMI, and IOP. In the CRVO-affected eyes, narrower relative retinal arteriolar calibers (p = 0.041) and wider relative venular calibers (p = 0.011) were independent risk factors compared with the CRVO-contralateral normal eyes when adjusting for IOP. We concluded that BRVO may be more associated with cerebrovascular diseases, and CRVO may be correlated with primary angle glaucoma. The geometric characteristics difference between the retinal and cerebrovascular may explain the pathological difference between CRVO and BRVO.

Retinal vascular dynamics: A window for observing an irregular heartbeat. A case report.

OBJECTIVE: We aimed to characterize several aspects of retinal vascular dynamics in a patient with arrythmia in order to elicit additional diagnostic information on microvascular dysfunction. METHODS: A 68-year-old male patient with arrythmia and an age- and gender-matched control subject underwent ocular examination including dynamic retinal vessel assessment with flicker light provocation. Retinal vessel diameters were measured continuously following a standard protocol (IMEDOS Systems, Jena, Germany). The data were evaluated using methods of signal analysis. RESULTS: Retinal vessel response following flicker provocation as well as local structural and functional behavior of retinal vessels were comparable between both individuals. The arrhythmia case demonstrated irregular arterial and venous heart rate (HR) pulsation with an average frequency of 1 Hz. Moreover, the case showed a higher magnitude and larger periods of low-frequency retinal vessel oscillations as well as lower periodicity of both HR pulsations and low-frequency vasomotions. CONCLUSIONS: Besides numerical examination of irregular HR pulsations in case of arrhythmia, from the direct noninvasive assessment of retinal vessel dynamics one can derive more detailed information on microvascular function including the whole spectrum of retinal arterial and venous pulsations and vasomotions. This may have implications for health screening not limited to atrial fibrillation.

Early remodeling and loss of light-induced dilation of retinal small arteries in CADASIL.

A major hurdle to therapeutic development in cerebral small vessel diseases is the lack of in-vivo method that can be used repeatedly for evaluating directly cerebral microvessels. We hypothesised that Adaptive Optics (AO), which allows resolution images up to 1-2 µm/pixel at retinal level, could provide a biomarker for monitoring vascular changes in CADASIL, a genetic form of such condition. In 98 patients and 35 healthy individuals, the wall to lumen ratio (WLR), outer and inner diameter, wall thickness and wall cross-sectional area were measured in a parapapillary and/or paramacular retinal artery. The ratio of vessel diameters before and after light flicker stimulations was also calculated to measure vasoreactivity (VR). Multivariate mixed-model analysis showed that WLR was increased and associated with a larger wall thickness and smaller internal diameter of retinal arteries in patients. The difference was maximal at the youngest age and gradually reduced with aging. Average VR in patients was less than half of that of controls since the youngest age. Any robust association was found with clinical or imaging manifestations of the disease. Thus, AO enables the detection of early functional or structural vascular alterations in CADASIL but with no obvious link to the clinical or imaging severity.

The vasoactive effects of bradykinin, vasoactive intestinal peptide, calcitonin gene-related peptide and neuropeptide Y depend on the perivascular tissue in porcine retinal arterioles in vitro.

PURPOSE: The retina contains a number of vasoactive neuropeptides and corresponding receptors, but the role of these neuropeptides for tone regulation of retinal arterioles has not been studied in detail. METHODS: Porcine arterioles with preserved perivascular retinal tissue were mounted in a wire myograph, and the tone was measured after the addition of increasing concentrations of bradykinin, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), substance P (SP), calcitonin gene-related peptide (CGRP) and brain natriuretic peptide (BNP). The experiments were performed during inhibition of the synthesis of nitric oxide (NO), prostaglandins and dopamine and were repeated after removal of the perivascular retinal tissue. RESULTS: Bradykinin, VIP and CGRP induced significant concentration-dependent dilatation and NPY significant concentration-dependent contraction of the arterioles in the presence of perivascular retinal tissue (p < 0.03 for all comparisons) but not on isolated arterioles. BNP and SP had no effect on vascular tone. The NOS inhibitor L-NAME reduced bradykinin- and VIP-induced relaxation (p < 0.001 for both comparisons), whereas none of the other inhibitors influenced the vasoactive effects of the studied neuropeptides. CONCLUSION: The effects of neuropeptides on the tone of retinal arterioles depend on the perivascular retinal tissue and may involve effects other than those mediated by nitric oxide, prostaglandins and adrenergic compounds. Investigation of the mechanisms underlying the vasoactive effect of neuropeptides may be important for understanding and treating retinal diseases where disturbances in retinal flow regulation are involved in the disease pathogenesis.

A prospective observation of influence of anti-VEGF on optic disc vasculature in nAMD patients.

BACKGROUND: This study aims to investigate the short-term changes in relatively normal retinal vessels following anti-vascular endothelial growth factor (anti-VEGF) therapy in nAMD patients, an area that currently represents a research gap. METHODS: In this prospective study, we enrolled patients newly diagnosed with neovascular age-related macular degeneration (nAMD) and received standardized monthly anti-VEGF therapy for three months. Follow-ups were conducted at baseline and 1-week, 1-month, 2-months and 3-months post first injection. Assessment indicators included radial peripapillary capillary vascular density (RPC-VD) and retinal nerve fiber layer (RNFL) thickness in different optic disk regions using optical coherence tomography angiography, as well as intraocular pressure (IOP). RESULTS: 68 nAMD patients (68 eyes) were included in this study. Significant reductions of RPC-VD and increases of RNFL thickness primarily in the nasal regions were observed 1-week post anti-VEGF (adjusted P < 0.05). Significant negative correlations were found between 1-week changes in RPC-VD and RNFL thickness in the nasal sectors (P < 0.05). From 1 to 3 months post-injection, RPC-VD and RNFL thickness essentially returned to baseline levels. Throughout the follow-up periods, IOP remained stable (P > 0.05). CONCLUSION: Anti-VEGF treatments transiently influence the relatively normal retinal vessels, which might lead to nerve fiber edema, predominantly on the nasal side of the optic disk.

Antiangiogenic activity of photobiomodulation in experimental model using chorioallantoic embryonic membrane of chicken eggs / Atividade antiangiogênica da fotobiomodulação em modelo experimental usando membrana embrionária corioalantóide de ovos de galinhas

ABSTRACT Purpose: The purpose of this study was to investigate the vascular effects of photobiomodulation using a light-emitting diode on the chorioallantoic embryonic membrane of chicken eggs grouped into different times of exposure and to detect the morphological changes induced by the light on the vascular network architecture using quantitative metrics. Methods: We used a phototherapy device with light-emitting diode (670 nm wavelength) as the source of photobiomodulation. We applied the red light at a distance of 2.5 cm to the surface of the chorioallantoic embryonic membrane of chicken eggs in 2, 4, or 8 sessions for 90 s and analyzed the vascular network architecture using AngioTool software (National Cancer Institute, USA). We treated the negative control group with 50 μl phosphate-buffered-saline (pH 7.4) and the positive control group (Beva) with 50 μl bevacizumab solution (Avastin, Produtos Roche Químicos e Farmacêuticos, S.A., Brazil). Results: We found a decrease in total vessel length in the Beva group (24.96% ± 12.85%) and in all the groups that received 670 nm red light therapy (2× group, 34.66% ± 8.66%; 4× group, 42.42% ± 5.26%; 8× group, 38.48% ± 6.96%), compared with the negative control group. The fluence of 5.4 J/cm2 in 4 sessions (4×) showed more regular vessels. The number of junctions in the groups that received a higher incidence of 670 nm red light (4× and 8×) significantly decreased (p<0.0001). Conclusion: Photo-biomodulation helps reduce vascularization in chorioallantoic embryonic membrane of chicken eggs and changes in the network architecture. Our results open the possibility of future clinical studies on using this therapy in patients with retinal diseases with neovascular components, especially age-related macular degeneration.

RESUMO Objetivo: investigar os efeitos vasculares da foto-biomodulação com diodo emissor de luz utilizando membrana embrionária corioalantóide de ovos de galinhas em grupos com diferentes tempos de exposição e detectar as alterações morfológicas por meio de métricas quantitativas promovidas pela luz na arquitetura da rede vascular. Métodos: Um aparelho de fototerapia com diodo emissor de luz no comprimento de onda de 670 nm foi usado como fonte de fotobiomodulação. A luz vermelha foi aplicada a uma distância de 2,5 cm da superfície da membrana embrionária corioalantóide em 2, 4 ou 8 sessões de 90 s a arquitetura da rede vascular foi analisada por meio do software AngioTool (National Cancer Institute, USA). Usamos um grupo controle negativo tratado com 50 µL de solução salina tamponada com fosfato (PBS) pH 7,4 e um grupo controle positivo (Beva) tratado com 50 µL de solução de bevacizumabe (Avastin, Produtos Roche Químicos e Farmacêuticos S.A., Brasil). Resultados: Uma diminuição no comprimento total do vaso foi detectada para o grupo Beva (24,96 ± 12,85%), e para todos os grupos que receberam terapia de luz vermelha de 670 nm, 34,66 ± 8,66% (2x), 42,42 ± 5,26% (4x) e 38,48 ± 6,96% (8x) em comparação ao grupo controle. A incidência de 5,4 J/cm2 em 4 sessões (4x) mostrou vasos mais regulares. A redução foi mais intensa nos grupos que receberam maior incidência de luz vermelha de 670 nm (4x e 8x). Conclusão: A fotobiomodulação contribui para a redução da vascularização nos vasos da membrana embrionária corioalantóide de ovos de galinhas e mudanças na arquitetura da rede. Os achados deste experimento abrem a possibilidade de considerar um estudo clínico usando esta terapia em pacientes com doenças retinais com componentes neovasculares, especialmente degeneração macular relacionada à idade.