The Guangzhou Twin Eye Study (GTES) is a cohort of twins living in South China that has been longitudinally followed for more than 15 years. This study has extensively investigated the heritability of myopia and the influence of environmental factors, producing significant and far-reaching impacts. GTES has found a high heritability of axial length and peripheral refraction, the significant role of education in myopia progression, and established prediction model for myopia onset and progression. The study has also explore the impact of both genetic and environmental factors on myopia development. By reviewing the major findings on myopia from the GTES, we hope to better inform public health strategies and clinical practices aimed at mitigating the global myopia epidemic.

The Guangzhou Twin Eye Study (GTES) is a cohort of twins living in South China that has been longitudinally followed for more than 15 years. This study has extensively investigated the heritability of myopia and the influence of environmental factors, producing significant and far-reaching impacts. GTES has found a high heritability of axial length and peripheral refraction, the significant role of education in myopia progression, and established prediction model for myopia onset and progression. The study has also explore the impact of both genetic and environmental factors on myopia development. By reviewing the major findings on myopia from the GTES, we hope to better inform public health strategies and clinical practices aimed at mitigating the global myopia epidemic.

Aims: To identify incident macular atrophy and evaluate antecedent anatomic alterations in eyes with neovascular age-related macular degeneration (NVAMD) that were treated with anti-vascular endothelial growth factor (anti-VEGF) agents. Methods: All patients treated with anti-VEGF agents for NVAMD by one of the authors during the 2014 calendar year who had follow up ≥ 12 months had evaluation of all SD-OCT scans from first treatment (usually prior to 2014) to last follow up through June 2018. Results: The ascertainment procedure identified 342 eyes of 278 patients with NVAMD among which 47 developed macular atrophy. The median time from treatment initiation to development of macular atrophy was 29.6 (interquartile range, 17.7-43.4) months. Three macular alterations were identified in areas that developed atrophy (some eyes had more than one); collapse of a vascularized pigment epithelial detachment (PED) and regression of choroidal neovascularization (CNV) in 25 eyes, development of subretinal hyper-reflective material and/or subretinal fibrosis in 15 eyes, or atrophy occurring in association with large drusen and pigmentary changes resulting in an arc of atrophy in a pattern typically referred to as geographic atrophy in 13 eyes. Conclusions: These data suggest that in some instances CNV may compensate for choroidal ischemia and the loss of CNV may expose retinal pigmented epithelial cells and photoreceptors to ischemic damage and atrophy.

Aims: To identify incident macular atrophy and evaluate antecedent anatomic alterations in eyes with neovascular age-related macular degeneration (NVAMD) that were treated with anti-vascular endothelial growth factor (anti-VEGF) agents. Methods: All patients treated with anti-VEGF agents for NVAMD by one of the authors during the 2014 calendar year who had follow up ≥ 12 months had evaluation of all SD-OCT scans from first treatment (usually prior to 2014) to last follow up through June 2018. Results: The ascertainment procedure identified 342 eyes of 278 patients with NVAMD among which 47 developed macular atrophy. The median time from treatment initiation to development of macular atrophy was 29.6 (interquartile range, 17.7-43.4) months. Three macular alterations were identified in areas that developed atrophy (some eyes had more than one); collapse of a vascularized pigment epithelial detachment (PED) and regression of choroidal neovascularization (CNV) in 25 eyes, development of subretinal hyper-reflective material and/or subretinal fibrosis in 15 eyes, or atrophy occurring in association with large drusen and pigmentary changes resulting in an arc of atrophy in a pattern typically referred to as geographic atrophy in 13 eyes. Conclusions: These data suggest that in some instances CNV may compensate for choroidal ischemia and the loss of CNV may expose retinal pigmented epithelial cells and photoreceptors to ischemic damage and atrophy.

Abstract: Retinal hemangioblastomas (RHs) are among the most common manifestations of von Hippel-Lindau (VHL) disease, an autosomal dominant genetic disorder that predisposes individuals to various tumors, particularly in the retina, central nervous system, kidney, adrenal gland, pancreas, and reproductive tract. VHL disease arises from variants in the VHL tumor suppressor gene, leading to the loss of VHL protein function. This protein regulates the degradation of hypoxia-inducible factors (HIFs) under normal oxygen conditions, but, in VHL disease, the loss of functional VHL protein results in the stabilization of HIFs, particularly HIF-2α, even in normoxia. The persistent activity of HIF-2α drives the overexpression of factors including transforming growth factor alpha (TGF-α), platelet-derived growth factor beta (PDGF-β), epidermal growth factor receptor (EGFR), glucose transporter 1 (GLUT-1) and vascular endothelial growth factor (VEGF) and others. Histologically, these tumors consist of tightly packed capillaries surrounded by stromal cells, which are the primaryneoplastic components. Clinically, RHs often represent one of the earliest manifestations of VHL disease and can lead to significant visual impairment or blindness if untreated. Current conventional treatment approaches include ablative therapies such as laser photocoagulation and cryotherapy, both of which are destructive, and can be successful if the tumors are of amenable size and location. Intravitreal anti-VEGF therapies are administered to reduce retinal edema. Effective therapies for large tumors and those located on the optic nerve are severely limited. However, recent advances in our understanding of the HIF-VEGF pathway have led to the development of targeted therapies, such as HIF-2α inhibitors like belzutifan, which have demonstrated promising results in reducing tumor burden and improving outcomes. These novel treatments offer hope for more effective and less invasive management of RHs within the broader context of VHL disease.

Abstract: Retinal hemangioblastomas (RHs) are among the most common manifestations of von Hippel-Lindau (VHL) disease, an autosomal dominant genetic disorder that predisposes individuals to various tumors, particularly in the retina, central nervous system, kidney, adrenal gland, pancreas, and reproductive tract. VHL disease arises from variants in the VHL tumor suppressor gene, leading to the loss of VHL protein function. This protein regulates the degradation of hypoxia-inducible factors (HIFs) under normal oxygen conditions, but, in VHL disease, the loss of functional VHL protein results in the stabilization of HIFs, particularly HIF-2α, even in normoxia. The persistent activity of HIF-2α drives the overexpression of factors including transforming growth factor alpha (TGF-α), platelet-derived growth factor beta (PDGF-β), epidermal growth factor receptor (EGFR), glucose transporter 1 (GLUT-1) and vascular endothelial growth factor (VEGF) and others. Histologically, these tumors consist of tightly packed capillaries surrounded by stromal cells, which are the primaryneoplastic components. Clinically, RHs often represent one of the earliest manifestations of VHL disease and can lead to significant visual impairment or blindness if untreated. Current conventional treatment approaches include ablative therapies such as laser photocoagulation and cryotherapy, both of which are destructive, and can be successful if the tumors are of amenable size and location. Intravitreal anti-VEGF therapies are administered to reduce retinal edema. Effective therapies for large tumors and those located on the optic nerve are severely limited. However, recent advances in our understanding of the HIF-VEGF pathway have led to the development of targeted therapies, such as HIF-2α inhibitors like belzutifan, which have demonstrated promising results in reducing tumor burden and improving outcomes. These novel treatments offer hope for more effective and less invasive management of RHs within the broader context of VHL disease.

Background: Meningeal carcinomatosis (MC) is a rare and serious complication associated with advanced hematologic and solid tumors. It can present with various ocular manifestations, and diagnosis is typically confirmed through magnetic resonance imaging and cerebrospinal fluid (CSF) analysis. Treatment often involves a combination of surgery, chemotherapy, and/or radiation; however, the disease is incurable, with a very low survival rate.

Case presentation: A 46-year-old woman presented to the ophthalmology department with complaints of vision loss. Funduscopy revealed a severely swollen optic disc (Frisen grade 5) with no visible optic disc margin and splinter hemorrhages. A contrast-enhanced chest computed tomography scan showed pulmonary nodules in the apex of the left lung. Analysis of CSF obtained through lumbar puncture confirmed the presence of malignant cells compatible with a diagnosis of MC.

Conclusions: MC is a severe complication of systemic cancer with a poor prognosis. Given that ocular symptoms can occasionally be the initial presentation, MC should be considered in patients experiencing vision loss or diplopia, even in the absence of an intraocular cause, neurologic symptoms, or a known history of systemic cancer. Comprehensive systemic examinations of major organs are crucial for early detection, diagnosis, and management of MC.

Background: Meningeal carcinomatosis (MC) is a rare and serious complication associated with advanced hematologic and solid tumors. It can present with various ocular manifestations, and diagnosis is typically confirmed through magnetic resonance imaging and cerebrospinal fluid (CSF) analysis. Treatment often involves a combination of surgery, chemotherapy, and/or radiation; however, the disease is incurable, with a very low survival rate.

Case presentation: A 46-year-old woman presented to the ophthalmology department with complaints of vision loss. Funduscopy revealed a severely swollen optic disc (Frisen grade 5) with no visible optic disc margin and splinter hemorrhages. A contrast-enhanced chest computed tomography scan showed pulmonary nodules in the apex of the left lung. Analysis of CSF obtained through lumbar puncture confirmed the presence of malignant cells compatible with a diagnosis of MC.

Conclusions: MC is a severe complication of systemic cancer with a poor prognosis. Given that ocular symptoms can occasionally be the initial presentation, MC should be considered in patients experiencing vision loss or diplopia, even in the absence of an intraocular cause, neurologic symptoms, or a known history of systemic cancer. Comprehensive systemic examinations of major organs are crucial for early detection, diagnosis, and management of MC.

Purpose: To report on surgical outcomes of removing subfoveal nodules and to evaluate the histopathological findings of subfoveal nodules in pediatric patients with coats’ disease. Methods: This was a retrospective, interventional case series in which 6 pediatric patients had large (>1 disk diameter) subfoveal nodules. Vitrectomy and excision of subfoveal nodules with silicon oil tamponade were performed. Silicon oil was removed 3 months later. Results: This study was carried out in 6 patients with a mean follow-up of 9.2±1.5 months (range: 7-11 months), and the mean age was 5.2±2.4 years (range: 2-8 years). Preoperative visual acuity ranged from light perception (LP) to 20/250, and postoperative visual acuity ranged from LP to 20/200. Histopathology revealed nodules composed of proliferating fibrous tissue, hyaline degeneration with foamy histiocytes, focal myofibroblast hyperplasia, ossified tissue, and cholesterol fissures, with chronic cellular infiltration. No nodules regressed during the follow-up period. Conclusion: Certain eyes of pediatric patients with coats’ disease who underwent subfoveal nodule removal and no evidence of nodule regression may benefit from submacular surgery. Histopathological findings revealed that anti-proliferative and anti-fibrotic agents could be targets for treating coats disease.

Purpose: To report on surgical outcomes of removing subfoveal nodules and to evaluate the histopathological findings of subfoveal nodules in pediatric patients with coats’ disease. Methods: This was a retrospective, interventional case series in which 6 pediatric patients had large (>1 disk diameter) subfoveal nodules. Vitrectomy and excision of subfoveal nodules with silicon oil tamponade were performed. Silicon oil was removed 3 months later. Results: This study was carried out in 6 patients with a mean follow-up of 9.2±1.5 months (range: 7-11 months), and the mean age was 5.2±2.4 years (range: 2-8 years). Preoperative visual acuity ranged from light perception (LP) to 20/250, and postoperative visual acuity ranged from LP to 20/200. Histopathology revealed nodules composed of proliferating fibrous tissue, hyaline degeneration with foamy histiocytes, focal myofibroblast hyperplasia, ossified tissue, and cholesterol fissures, with chronic cellular infiltration. No nodules regressed during the follow-up period. Conclusion: Certain eyes of pediatric patients with coats’ disease who underwent subfoveal nodule removal and no evidence of nodule regression may benefit from submacular surgery. Histopathological findings revealed that anti-proliferative and anti-fibrotic agents could be targets for treating coats disease.

Background: Type 3 macular neovascularization (MNV3) is an important subtype of neovascular age-related macular degeneration. Previously, we established an advanced MNV3-like mouse model by knocking out the Vhl, Rb1, and p107 genes in the retinal progenitors (Rb1/p107/Vhl TKO model). This study investigates the role of the p107 protein (also called Rb transcriptional corepressor like 1, Rbl1) on retinal blood vessels in the VhlKO retina. Methods: By breeding the retinal-specific alpha-Cre mice with Vhl ^floxed mice and p107 ^-/-mice, we got VhlKO, p107KO, and p107/VhlDKO mice. Whole mount retinal IB4 staining, and fundus fluorescein angiography (FFA) were performed to evaluate the retinal vascular vessels. Immunofluorescence staining studied retinal cell types, cell proliferation, and cell death. RNA sequencing, chromatin immunoprecipitation (CHIP), and dual luciferase reporter assay were also performed to study the retinal transcriptome, the binding of p107 protein to the promoter region of Hif target genes, and the effect of the p107 protein on the transcriptional activity of the Hif target genes. Results: p107/VhlDKO mice have delayed regression of hyaloid vessels, retinal degeneration, and retinal neovascularization. The p107 protein significantly inhibits the Hif pathway activity in VhlKO retinas. It can also bind to the promoter regions and suppress the transcriptional activity of several Hif target genes, including Vegfa, Kdr, and Tek. Conclusions:The p107 protein inhibits angiogenesis in the VhlKO retina, as it can bind and inhibit Hif target genes related to retinal angiogenesis.

Background: Type 3 macular neovascularization (MNV3) is an important subtype of neovascular age-related macular degeneration. Previously, we established an advanced MNV3-like mouse model by knocking out the Vhl, Rb1, and p107 genes in the retinal progenitors (Rb1/p107/Vhl TKO model). This study investigates the role of the p107 protein (also called Rb transcriptional corepressor like 1, Rbl1) on retinal blood vessels in the VhlKO retina. Methods: By breeding the retinal-specific alpha-Cre mice with Vhl ^floxed mice and p107 ^-/-mice, we got VhlKO, p107KO, and p107/VhlDKO mice. Whole mount retinal IB4 staining, and fundus fluorescein angiography (FFA) were performed to evaluate the retinal vascular vessels. Immunofluorescence staining studied retinal cell types, cell proliferation, and cell death. RNA sequencing, chromatin immunoprecipitation (CHIP), and dual luciferase  reporter assay were also performed to study the retinal transcriptome, the binding of p107 protein to the promoter region of Hif target genes, and the effect of the p107 protein on the transcriptional activity of the Hif target genes. Results: p107/VhlDKO mice have delayed regression of hyaloid vessels, retinal degeneration, and retinal neovascularization. The p107 protein significantly inhibits the Hif pathway activity in VhlKO retinas. It can also bind to the promoter regions and suppress the transcriptional activity of several Hif target genes, including Vegfa, Kdr, and Tek. Conclusions:The p107 protein inhibits angiogenesis in the VhlKO retina, as it can bind and inhibit Hif target genes related to retinal angiogenesis.

背景：目前已有研究报道了一种MATLAB的定制算法，用于Triton光学相干断层扫描血管成像(optical coherence tomography angiography，OCTA)图像的中心凹无血管区(fovea avascular zone，FAZ)的自动测量。由于这种算法非开源，且难以获取，因而大大限制了其在临床实践和科学研究中的应用。本研究提出一种用于Triton OCTA图像的FAZ自动分割的开源算法，即Smooth Level Sets macro(SLSM)算法，并将其测量结果与MATL AB和人工方法相比较，评估该算法分割的准确性和可靠性。方法：纳入35位健康受试者的35只健眼，选用Triton OCTA机器中的3 mm×3 mm扫描模式，对其黄斑区进行连续4次扫描。分别用人工和自动方法(包括MATL AB和SLSM)，测量浅层毛细血管图像中FAZ的面积、周长和圆度。分析各种自动算法的准确性、重复性，以及与人工方法结果的一致性。结果：SLSM算法的准确性仅低于人工方法，而高于MATLAB算法(Dice系数：人工方法，0.9568；SLSM，0.9506；MATL AB，0.9483)。SLSM和MATL AB测量FAZ面积的重复性均很高[组内相关系数(intraclass correlation coefficient，ICC)：SLSM，0.987；MATLAB，0.983]。SLSM、MATLAB测量FAZ面积的结果均与人工方法呈很高的一致性(ICC：SLSM，0.973；MATL AB，0.968)。结论：SLSM在Triton OCTA图像的FAZ自动分割中的准确性高于MATL AB，其测量结果与人工测量结果很相近。作为免费和开源的资源，SLSM有望成为Triton OCTA图像中有效可靠的FAZ自动分割和测量方法。

Background: Previous studies have proposed an automated customized program named MATLAB used in the foveal avascular zone (FAZ) measurements in Triton optical coherence tomography angiography (OCTA) images. But it is not open-source and not easy to obtain, which will largely restrict its application in clinical practice and medical research. In this study, we aimed to investigate the feasibility of the Smooth Level Sets macro (SLSM), a free and open-source program, and compared with the manual measurements and MATLAB in the FAZ quantification in Triton OCTA. Methods: Thirty-five eyes of 35 healthy subjects were scanned four times continuously using Triton OCTA. Manual and automated methods including the SLSM and MATLAB were used in the FAZ metrics (area, perimeter, and circularity) of the superficial capillary plexus. The accuracy, repeatability of all methods, and agreement between automated and manual methods were analyzed. Results: The SLSM presented higher accuracy with a higher average Dice coefficient (0.9506) than MATLAB (0.9483), which was just second to the manual method (0.9568). Both the SLSM [intraclass correlation coefficient (ICC) =0.987; coefficient of variation (CoV) =3.935%] and MATLAB (ICC =0.983; CoV =4.165%) showed excellent repeatability for the FAZ area. They also had excellent agreement with manual measurement (SLSM, ICC =0.973; MATLAB, ICC =0.968). Conclusion: The SLSM exhibits better accuracy than MATLAB in the automated FAZ measurement in Triton OCTA, the results of which were comparable to those obtained by manual measurement. This free and open-source program may be an accessible and feasible option for automated FAZ segmentation on Triton OCTA images.