Efficacy and safety of anti-vascular endothelial growth agents for the treatment of polypoidal choroidal vasculopathy: A systematic review and meta-analysis

There remains limited agreement regarding the efficacy and safety of different antivascular endothelial growth factor (anti-VEGF) agents for the management of polypoidal choroidal vasculopathy (PCV). Our meta-analysis compares different anti-VEGF agents for PCV treatment. Ovid MEDLINE, EMBASE, and Cochrane Library were systematically searched from January 2000 to July 2022. We included articles comparing the efficacy and safety of different anti-VEGF agents, specifically bevacizumab (BEV), ranibizumab (RAN), aflibercept AFL), and brolucizumab (BRO), for patients with PCV. 10,440 studies were identified, 122 underwent full-text review, and seven were included. One study was a randomized trial, and six were observational studies. Ranibizumab and aflibercept were associated with a similar best-corrected visual acuity (BCVA) at the last visit in three observational studies (P = 0.10), similar retinal thickness at the last visit in two observational studies (P = 0.85). One observational study comparing BEV versus RAN found comparable outcomes for final BCVA, retinal thickness, and polyp regression. One randomized trial on BRO versus AFL found comparable outcomes for improvement in BCVA, while anatomical outcomes favored BRO. The available evidence suggests that final BCVA is comparable across different anti-VEGF agents, however, further investigation is warranted due to paucity of evidence.     

Responses of Types 1 and 2 Neovascularization in Age-Related Macular Degeneration to Anti-Vascular Endothelial Growth Factor Treatment: Optical Coherence Tomography Angiography Analysis

Purpose: To compare the responses of types 1 (sub-pigment epithelial) and 2 (subretinal) neovascularization in neovascular age-related macular degeneration (AMD) to anti-vascular endothelial growth factor (VEGF) treatment.

Methods: Fifty-five treatment-naïve neovascular AMD eyes (53 patients) were retrospectively included for analysis. All patients were treated with three loading injections of anti-VEGF agent, followed by further injections as required. The lesion size and vascular density of type 1 and 2 lesions before and after treatment for 12 months were analyzed using optical coherence tomography angiography (OCTA).

Results: The mean lesion size of the type 1 neovascularization group (42 eyes) showed no significant change from 2.12 ± 1.01 mm² at baseline to 2.08 ± 0.91 mm² at 12 months (P = .682). However, the mean lesion size of type 2 neovascularization significantly decreased from 1.23 ± 0.93 mm² at baseline to 0.79 ± 0.61 mm² at 12 months (P = .022). The proportion of eyes with lesion sizes that decreased by more than 40% from baseline was also significantly higher for the type 2 compared to the type 1 neovascularization group (46.2% versus 11.9%, P = .007). Vascular density showed no significant changes for both groups after treatment and showed no association with the change in lesion size. There was no significant difference between the groups in terms of visual acuity improvement.

Conclusion: OCTA analysis revealed different responses to anti-VEGF treatment depending on the location of neovascularization in neovascular AMD. Type 2 neovascularization was significantly regressed compared to type 1 neovascularization after anti-VEGF treatment. However, the changes in vascular density and visual outcome showed no significant differences between groups after 12 months of treatment.     

Moderately Acidic pH Promotes Angiogenesis: An In Vitro and In Vivo Study

IntroductionThis study evaluated the effect of different pH values of 4.4, 5.4, 6.4, 7.4, 8.4, and 9.4 on angiogenesis.MethodsEndothelial cells were isolated from the mice molar teeth and placed in 42 Matrigel (Corning, NY)-coated wells, which were prepared and divided into 6 groups (n = 7). Synthetic tissue fluid was prepared and divided into 6 parts, and their pH values were adjusted to 4.4, 5.4, 6.4, 7.4, 8.4, and 9.4. A 2-mL volume from each group was diluted in the growth medium at a ratio of 1:3 and used for tubulogenesis assay. Forty-two 6-week-old mice in 6 groups (n = 7) were used for choroidal neovascularization (CNV). A 2-μL volume from each group or saline (control) was delivered by intravitreal injection on the day of laser application and 1 week later. Data on the number of nodes, the total length of the branches, and CNV areas (μm²) were determined using ImageJ software (National Institutes of Health, Bethesda, MD) and analyzed with 1-way analysis of variance and post hoc Tukey tests. The correlation was assessed between the tested variables.ResultsThe number of nodes decreased with changes in pH values as follows: 6.4 > 5.4 > 7.4 > 8.4 > 9.4 > 4.4. The total branch length decreased with pH value changes as follows: 6.4 > 4.4 > 6.4 > 7.4 > 8.4 > 9.4, and the CNV areas decreased with pH value changes as follows: 6.4 > 5.4 > 4.4 > 7.4 > 8.4 > 9.4.ConclusionsModerately acidic pH values (5.4 and 6.4) enhanced angiogenesis, whereas moderately alkaline pH values (8.4 and 9.4) suppressed angiogenesis.     

Correlation of ischemic ophthalmopathy with lacunar infarction

AIM: To investigate the effects of nintedanib thermo-sensitive hydrogel (NTH) on neovascularization and related markers in corneal alkali burns of Wistar rats. METHODS: NTH was prepared by grinding, and its phase-transition temperature was determined. Thirty specific-pathogen-free Wistar rats served as a model of corneal alkali burn in the right eye were randomly divided into 3 groups (n=10, each): model group treated with 0.9% saline once a day, NTH group with 0.2% nintedanib b.i.d, and dexamethasone (DEX) group with DEX ointment once a day. The left eye of rats served as the controls. The corneal transparency was observed under a slit-lamp microscope, and the area of neovascularization was calculated. On day 7, the rats were sacrificed, and the cornea was removed and embedded with paraffin, then stained with hematoxylin-eosin, and the expression of VEGFR-2 and CD31 in the corneal tissues of each group was detected by immunofluorescence. RESULTS: The phase-transition temperature of nintedanib obtained by grinding was 37°C after adding artificial tears. The results of the alkali burn model indicated that the growth rate of neovascularization in the NTH group was slower than that in the model group, and the neovascularization area was significantly smaller than that in the model group (P<0.05). Moreover. CD31 and VEGFR-2 expression levels in the NTH group were significantly lower than those in the model group. CONCLUSION: NTH becomes colloidal at body temperature, which is beneficial for releasing the drug slowly and can significantly inhibit the neovascularization of corneal induced by alkali burn in rats.     

病理性近视脉络膜新生血管的诊断与治疗

病理性近视是全世界范围内引起患者视力下降的主要原因之一,在亚洲国家尤为多见。而脉络膜新生血管是病理性近视的最严重并发症之一,它可以引起眼底黄斑区病变,导致视力下降,出现中心暗点,视物变形,视野缺损等,如长期不治疗可能导致失明。光学相干断层扫描、光学相干断层扫描血管成像、荧光素眼底血管造影等检查方法在诊断病理性近视继发的脉络膜新生血管中起到很大帮助,可以较为明确的显示新生血管的位置,大小等,不论其是否处于活动期。目前对于病理性近视引起的脉络膜新生血管主要治疗方法有光动力治疗及抗血管内皮生长因子(VEGF)治疗,近年来,玻璃体腔内注射抗VEGF药物成为病理性近视与脉络膜新生血管的首选治疗方法,通过减少新生血管的形成,减轻黄斑区水肿,从而达到改善视力及更好的预后效果。论文主要综合整理近期关于病理性近视脉络膜新生血管的诊断及治疗的研究,为临床工作提供帮助。     

Updates of pathologic myopia

Complications from pathologic myopia are a major cause of visual impairment and blindness, especially in east Asia. The eyes with pathologic myopia may develop loss of the best-corrected vision due to various pathologies in the macula, peripheral retina and the optic nerve.Despite its importance, the definition of pathologic myopia has been inconsistent. The refractive error or axial length alone often does not adequately reflect the ‘pathologic myopia’. Posterior staphyloma, which is a hallmark lesion of pathologic myopia, can occur also in non-highly myopic eyes. Recently a revised classification system for myopic maculopathy has been proposed to standardize the definition among epidemiological studies. In this META-PM (meta analyses of pathologic myopia) study classification, pathologic myopia was defined as the eyes having chorioretinal atrophy equal to or more severe than diffuse atrophy.In addition, the advent of new imaging technologies such as optical coherence tomography (OCT) and three dimensional magnetic resonance imaging (3D MRI) has enabled the detailed observation of various pathologies specific to pathologic myopia. New therapeutic approaches including intravitreal injections of anti-vascular endothelial growth factor agents and the advance of vitreoretinal surgeries have greatly improved the prognosis of patients with pathologic myopia. The purpose of this review article is to provide an update on topics related to the field of pathologic myopia, and to outline the remaining issues which need to be solved in the future.     

脉络膜黑色素瘤的病理特点与预后

目的　分析脉络膜黑色素瘤的病理特点及预后影响因素。方法　对天津市眼科医院2003年10月至2014年3月入院的31例（31眼）经病理证实的脉络膜黑色素瘤进行回顾性研究，总结病理特点及预后影响因素。结果　脉络膜黑色素瘤31例（31眼）中男18例（58.1%），女13例（41.9%）；均为单眼发病，右眼17例（54.8%），左眼14例（45.2%）；年龄30~71岁，平均52.5岁。肿瘤位于睫状体者7眼，位于赤道后者15眼，位于旁视神经者4眼，位于赤道前者5眼。瘤体呈蘑菇状者6眼，呈圆顶状者5眼，呈类圆形者3眼，呈半圆形者4眼，呈扁平形者12眼，呈弥漫状者1眼。31眼中，大肿瘤8眼，中等肿瘤23眼。肿瘤细胞类型:梭形细胞型7眼（眼内期4眼，青光眼期1眼，眼外蔓延期2眼），上皮细胞型4眼（眼内期3眼，眼外蔓延期1眼），混合细胞型20眼（眼内期15眼，青光眼期2眼，眼外蔓延期2眼，全身转移期1眼）。肿瘤细胞向巩膜外蔓延程度:Ⅰ级15眼，Ⅱ级6眼，Ⅲ级3眼，Ⅳ级7眼。在Ⅳ级中有4眼伴有大量坏死，大部分为大肿瘤。眶内蔓延途径:沿巩膜导管和巩膜涡静脉蔓延者6眼；直接侵犯巩膜、向眼球外蔓延者5眼；沿筛板直接蔓延者1眼；侵犯视网膜、睫状体、虹膜、结膜者4眼。随访22例患者中有2例死亡，均为混合细胞型并发肝转移，存活时间为术后17个月（全身转移期）和28个月（眼内期）。结论　脉络膜黑色素瘤的预后受多种因素的影响（位置、形状和体积、瘤细胞类型、扩散途径等），沿巩膜导管、巩膜涡静脉蔓延和侵犯巩膜、向眼球外蔓延是主要的蔓延途径。