Blocking Ocular Sympathetic Activity Inhibits Choroidal Neovascularization

Purpose: To investigate how modulating ocular sympathetic activity affects progression of choroidal neovascularization (CNV), a hallmark feature of wet age-related macular degeneration (AMD).Methods: In the first of two studies, Brown Norway rats underwent laser-induced CNV and were assigned to one of the following groups: daily eye drops of artificial tears (n = 10; control group); daily eye drops of the β-adrenoreceptor agonist isoproterenol (n = 10); daily eye drops of the β-adrenoreceptor antagonist propranolol (n = 10); sympathetic internal carotid nerve (ICN) transection 6 weeks prior to laser-induced CNV (n = 10). In the second study, rats underwent laser-induced CNV followed by ICN transection at different time points: immediately after the laser injury (n = 6), 7 days after the laser injury (n = 6), and sham surgery 7 days after the laser injury (n = 6; control group). All animals were euthanized 14 days after laser application. CNV development was quantified with fluorescein angiography and optical coherence tomography (in vivo), as well as lesion volume analysis using 3D confocal reconstruction (postmortem). Angiogenic growth factor protein levels in the choroid were measured with ELISA.Results: In the first study, blocking ocular sympathetic activity through pharmacological or surgical manipulation led to a 75% or 70% reduction in CNV lesion volume versus the control group, respectively (P < 0.001). Stimulating ocular sympathetic activity with isoproterenol also led to a reduction in lesion volume, but only by 27% versus controls (P < 0.05). VEGF protein levels in the choroid were elevated in the three treatment groups (P < 0.01). In the second study, fluorescein angiography and CNV lesion volume analysis indicated that surgically removing the ocular sympathetic supply inhibited progression of laser-induced CNV, regardless of whether ICN transection was performed on the same day or 7 days after the laser injury.Conclusion: Surgical and pharmacological block of ocular sympathetic activity can inhibit progression of CNV in a rat model. Therefore, electrical block of ICN activity could be a potential bioelectronic medicine strategy for treating wet AMD.

Choroidal Morphologic and Vascular Features in Patients With Myopic Choroidal Neovascularization and Different Levels of Myopia Based on Image Binarization of Optical Coherence Tomography

Purpose: To characterize the choroidal morphologic and vascular features in different levels of myopes and patients with myopic choroidal neovascularization (mCNV).Methods: A total of 148 subjects were enrolled in this cross-sectional study, including 78 low-to-moderate myopes (LMM), 53 high myopes (HM), and 17 high myopic patients with mCNV. Ocular biometrics were measured using an optical low-coherence reflectometry device. Retinal and choroidal imaging was performed using enhanced depth imaging (EDI) spectral domain optical coherence tomography (OCT). Retinal parameters including retinal thickness and retinal volume were obtained from a built-in software. Binarization technique was adopted to investigate choroidal parameters including choroidal thickness (CT), vascular area, stromal area, and choroidal vascularity index (CVI). Choroidal parameters were measured at five locations to cover as much area of choroid as possible, and their patterns of distribution were further analyzed.Results: Patients with mCNV had an atrophic retina of comparable thickness to HM (273.65 ± 17.28 vs. 276.49 ± 13.29 μm, p = 0.47), but the choroid was thinner than that of HM (153.94 ± 15.12 vs. 236.09 ± 38.51 μm, p < 0.001). Subfoveal CVI was greatest in the mCNV eyes (0.651 ± 0.009), followed by HM (0.645 ± 0.012) and LMM eyes (0.636 ± 0.012). Similar to CT, CVI was also found significantly different among these three groups at all five locations (p for trend < 0.001 for all locations). Axial length (AL) was negatively correlated with retinal volume (r = −0.236, p = 0.009), which is the only significant finding in associations between ocular factors and retinal parameters. Strong, negative correlations were identified between AL and subfoveal choroidal thickness (SFCT, r = −0.820, p < 0.001). However, AL was positively correlated with subfoveal CVI (r = 0.668, p < 0.001). CVI was greater in myopic eyes with thinner choroid (r = −0.578, p < 0.001). BCVA exhibited no significant association with CVI (r = 0.139, p = 0.092), but was negatively correlated with SFCT (r = −0.386, p < 0.001) and positively correlated with AL (r = 0.351, p < 0.001).Conclusion: Choroid in patients with mCNV was thinner yet more vascularized than that in HM and LMM subjects. CVI increased with a longer AL which was associated with a smaller SFCT, choroidal vascular area (VA), and total choroidal area (TCA). Better BCVA was achieved in subjects with thicker SFCT and shorter AL.

Mechanism of Hypoxia Inducible Factor-1α (HIF-1α) in Choroidal Neovascularization in Macular Lutea of High Myopia

To explore the changes in the expression of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in the process of choroidal neovascularization (CNV) in the macular area of cases with form deprivation myopia (FDM), in this study, 36 healthy mice were selected as research subjects for analysis. Specifically, they were randomly divided into test group (n = 18) and control group (n = 18). The right eye of the test group mice underwent form deprivation for 6 weeks to induce FDM, also known as FDM group. Five mice were randomly selected from FDM group and control group at 6 time points (before photocoagulation, at 7 d, 14 d, 21 d, 28 d, and 35 d after photocoagulation), respectively, for fluorescein angiography and hematoxylin-eosin staining (HE) staining to observe differences in the retina. It was found that the retina of Control group mice was well-structured with clear stratification, while that of the test group mice was severely damaged with a disordered structure, manifested as edema and swelling and damaged Bruch membrane and retinal pigment epithelium (RPE) layer. Furthermore, macrophages and RPE cells were observed in the photocoagulation area, and there was a high-fluorescence area with a blurred margin in the fundus, indicating the formation of new blood vessels. The immunohistochemical experiment revealed that within three weeks after the surgery, HIF-1α was highly expressed in the test group, and the expression level was obviously higher than the Control group. The real-time quantitative polymerase chain reaction (PCR) results showed that the expression level of VEGF and HIF-α in the test group was obviously higher than the Control group within three weeks after the surgery. The Western blot experiment was performed 1 week after the surgery, and it was noted that the expression level of VEGF and HIF-1α were higher in the test group versus the Control group. In summary, HIF-1α is instrumental in ocular CNV, which is also associated with VEGF.

Outcomes of conbercept therapy for choroidal neovascularization secondary to pathological myopia

AIM: To evaluate the one-year outcome of intravitreal conbercept injections for the treatment of choroidal neovascularization secondary to pathological myopia (pm-CNV) by optical coherence tomography angiography (OCTA). METHODS: The medical records of 26 consecutive eyes of 23 patients who received intravitreal injections of conbercept for pm-CNV with a follow-up of one year were retrospectively reviewed. All the patients were diagnosed by fundus fluorescein angiography (FFA) and OCTA at the first visit. All approaches were performed as “1+PRN” treatment. Outcomes included best-corrected visual acuity (BCVA), central foveal thickness (CFT) and the mean CNV area by OCTA. RESULTS: Mean Logarithm BCVA improved from (0.66±0.51) at baseline to (0.39±0.38) at one year (t=3.528, P=0.004). The CFT before treatment and after one year after were 275.08±48.74) μm and (205.15±43.74) μm respectively (t=4.630, P=0.001). The mean pm-CNV areas before treatment and after one year treatment were (0.48±0.24) mm2 and (0.15±0.11) mm2 respectively, with a significant difference among them (t=5.329, P=0.000). Twenty-one eyes had no needs after the first treatment. Four eyes received 2 injections and only one eye received 3 injections. No severe adverse events were noted relevant to the therapy. CONCLUSION: Intravitreal conbercept can improve the vision and relieve CFT and CNV area for the treatment of pm-CNV with “1+PRN” by OCTA for one year, however, long-term follow-up still need to be performed.

Myopic choroidal neovascularization: management issues remain

In the modern world, myopia continues to be one of the most common refractive errors and is considered a socially signifi cant problem, since it is a common cause of decreased vision. In connection with the growth of myopia, the risk of developing complications in the fundus increases, leading to the development of degenerative changes in the retina and an irreversible decrease in visual functions in young and middle-aged people. One of these complications is myopic choroidal neovascularization, which leads to a progressive, irreversible decrease in visual acuity and poor prognosis, and the process is often bilateral in nature. The tactics of managing patients with such complications has been determined: antiangiogenic therapy is used – intravitreal therapy with anti-VEGF drugs, which is currently the fi rst choice therapy for this pathology. But in some cases, antiangiogenic therapy is contraindicated, and the question arises about the tactics of managing such patients. The aim: to study treatment options for myopic choroidal neovascularization in patients with myopia in different situations.Material and methods. The paper presents two clinical observations of patients with mChNV, considers the tactics of their management. The patients underwent standard ophthalmological examination, optical coherence tomography (OCT) and OCT-Angio (OPTOPOL Technology, Poland).Conclusions. Women with myopia planning pregnancy need a thorough examination not only by a clinician, but also by an ophthalmologist, since it is necessary to take into account not only the degree of myopia and choose the optimal delivery method, but also to study the state of the retina for the timely diagnosis of degenerative changes in the fundus.

Choroidal neovascularization activity and structure by optical coherence tomography angiography in age related macular degeneration

Background. In economically developed countries, age-related macular degeneration (AMD) is the leading cause of visual disability among the population of the older age group. The main criterion for the anti-VEGF treatment of neovascular AMD is the activity of choroidal neovascularization (CNV), which is determined by its confi guration. The search for optimal criteria for quantifying the state of the macular region in order to decide on the appointment of anti-VEGF therapy continues.Aim: improving the effi ciency of diagnosis and treatment of AMD based on the assessment of the configuration of vascular system on the “Key to Diagnosis II” platform.Material and methods. The study included 341 patients: 64 % (218 patients, 267 eyes) with non-neovascular AMD, 36 % (123 patients, 174 eyes) – with neovascular AMD. 56 patients (58 eyes) had active type I CNV. Group 1A – active CNV before treatment (9 patients, 9 eyes), group 1B – non-active CNV after treatment with antiVEGF (9 patients, 9 eyes); control group – 10 patients (10 eyes) without AMD. Analysis of OCT-angio images of choriocapillaries included the isolation of CNV, its area, fractal dimension (Df) and the complexity of the vascular system (CVS) counting.Results. Group 1A: Df – 1.5871 ± 0.05, CVS – 2.29 ± 0.29, area – 11734 ± 4866; group 1B: Df – 1.6462 ± 0.08, CVS – 1.65 ± 0.18, area – 6797 ± 3818; control: Df – 1.9167 ± 0.06, CVS – 1, area – 0. Significant differences were found for CVS (p = 0.0003). Df correlates with the CNV area (p = 0.7) and is probably an unreliable parameter due to incomplete visualization of active CNV.Conclusions. CVS is a quantitative biomarker for determining the activity of type 1 CNV in patients with AMD and can serve as a parameter for convolutional neural networks training for automated analysis of OCT angiography images based on the “Key to Diagnosis II” platform