Since anti-vascular endothelial growth factor (VEGF) therapy has recently become the first-line treatment of wet age related macular degeneration in China, as well as retinopathy of prematurity, neovascular glaucoma and macular edema secondary to diabetic retinopathy or retinal vein occlusion in other countries. It is worth thinking about that how to perform anti-VEGF treatment properly to benefit more patients. We reviewed the fields of clinical researches to explore the best role of anti-VEGF treatment in prevention and treatment of retinal disease in future.
There are lots of imaging technologies in the ocular fundus disease field, including ultrasound biomicroscopy (UBM), fundus fluorescein angiography (FFA), indocynine green angiography (ICGA), fundus photograph (FP) and Optical Coherence Tomography (OCT). However there is no standard for image formats among various fundus imaging equipment, technology application processes, thus the relevant data cannot be compared and analyzed. And improper operation of the instruments causes unstable image quality or image missing. Also lack of appropriate evaluation guidelines results in different interpretation of same image data. These three factors not only affect the fundus imaging device application efficiency, limit the sharing of fundus imaging resource, but also hinder the development of fundus imaging diagnostic applications. Therefore, instrument types, data acquisition protocol and data presenting formats should be standardized for ocular fundus image acquisition. The technicians who operate the machine should be trained regularly to follow the standard operating procedure of data acquiring, thus to ensure integrity, truthful and reliable data is collected. In order to enhance the application efficiency of fundus imaging equipment, save public health resources, to promote fundus imaging diagnostic technology development, we need to develop evaluation guidelines for fundus image data, establish a comprehensive system including remote consultation center, reading center and quality control center.
Peripapillary intrachoroidal cavitation (PICC) is a common pathological change observed in high myopia. The exact pathogenesis of PICC is still unclear. Expansion and mechanical stretching of the peripapillary sclera, breakage and defect in the retina near the border of the myopic conus and communication between intrachoroidal cavity and the vitreous space may be important segments during the development of PICC. Color fundus photography shows a localized and well-circumscribed peripapillary lesion with yellow-orange colour, often accompanied by fundus changes, such as myopic conus excavation, optic disc tilting and inferotemporal retinal vein bending at the transition from the PICC to the myopic conus. However, the PICC lesion is not easy to be recognized in the fundus photography. Fluorescein angiography shows early hypofluorescence and later progressively staining in the lesion. Indocyanine green angiography shows hypofluorescence throughout the examination. Optical coherence tomography (OCT) is vital in diagnosing PICC. Hyporeflective cavities inside the choroid, sometimes communicating with the vitreous chamber, can be observed in OCT images. OCT angiography indicates lower vessel density or even absence of choriocapillary network inside or around PICC lesions.
Diabetic macular edema (DME) is the main cause of visual impairment in diabetic retinopathy patients. It mainly includes focal DME and diffuse DME, while DME of clinical significance needs timely intervention treatment. Optical coherence tomography is currently recognized as the most sensitive method to accurately diagnose DME. Currently, the common treatments of DME include intravitreal injection of anti-vascular endothelial growth factor (VEGF) or glucocorticoid and laser photocoagulation. Among them, anti-VEGF injection is becoming the first-line therapeutic, and corresponding individual treatment or combined treatment strategy should be selected according to the characteristics of DME and the specific conditions of patients. During the diagnosis and treatment of DME, attention should be paid to the systemic treatment of diabetes and the effect of diabetes-related neuroretinopathy on the therapeutic effect of DME. With the appearance of heterogeneity in the efficacy of anti-VEGF drugs, it remains to be further studied how to choose alternative therapeutics and when to replace them.
Retinal neuronal cells are crucial in the formation of vision. Injury or death of these cells may lead to irreversible damage to visual function due to their low regenerative capacity. The P2X7 receptor is a trimeric adenosine triphosphate (ATP)-gated cation channel. Recent studies have shown that P2X7 receptor plays a role in retinal neuronal death. In a series of animal models, when exposed to conditions of hypoxia or ischemia, elevated ocular pressure, trauma and exogenous agonists, P2X7 receptor activated by extracellular ATP can cause death of retinal neuronal cells such as retinal ganglion cells and photoreceptor cells through direct or indirect pathways. Blocking the expression and function of P2X7 receptor by its specific antagonist and gene knocking-out, the loss of retinal neuronal cells is significantly attenuated. P2X7 receptor may become a potential novel neuroprotective target for diseases related to the loss of retinal neurons.
Maculopathy caused by various fundus diseases in the late stage is a common cause of low vision. Medical technology is difficult to reverse the loss of macular function currently, so interventions that help improve the visual system, utilize residual visual function, and improve quality of life deserve attention. Damage to the fovea of the macula does not mean that the entire retinal function is impaired. There may be one or more retinal regions adjacent to the fovea that can serve as a fixation center. It is possible to form stable paracentral fixation, complete functional remodeling of the visual system, and effectively utilize residual visual function by taking appropriate training on these potential paracentral fixation points for most patients. In 2021, a clinical guideline has been published for low vision rehabilitation in China. In order to strengthen the precise management of diseases and develop a standard operating procedure for visual training specifically for patients with low vision due to macular disease, the National Clinical Research Center for Eye Diseases initiated and organized relevant domestic experts, utilizing the latest research experience at home and abroad, and through repeated discussions, this consensus (International Practice Guideline Registration Number: PREPARE-2023CN199) was formed as a reference for ophthalmologists, optometrists and rehabilitation physicians in their clinical research and practice.
Pathological myopia is one of the most challenging clinical diseases in the field of ophthalmology. The accurate definition, standard classification, disease evolution mechanism and disease prevention and treatment strategies are still under investigation. The development and application of artificial intelligence provides a powerful tool for the analysis of pathological myopia related data. More and more accurate data information is obtained in the clinical work and clinical research of pathological myopia through the standardized collection and acquisition of the fundus image data, the automatic segmentation and quantitative analysis of the fundus physiological structure, the automatic detection and analysis of the pathological myopia classic lesions and the clinical diagnosis and treatment decision aid, which helps ophthalmologists to understand the pathogenesis and evolution of pathological myopia.
Myopia has become a major problem that threatens human health worldwide. Complications caused by high myopia are one of the leading causes of low vision and blindness. As a chronic disease that seriously threatens ocular health in the clinical practice and public health fields, the prevention and control of high myopia should actively promote a tertiary prevention strategy, and take advantages of the latest fundus imaging technology and big data technology, artificial intelligence to explore the evolution mechanism of “myopia→high myopia→pathological myopia”. Special efforts should be focused on the establishment of a scientific myopia prediction model, implementation of effective high myopia monitoring and management, and early detection and treatment of complications of high myopia to reduce the incidence of low vision and blindness.
Intravitreal injection of anti-VEGF drugs has gradually become the first-line treatment for diabetic retinopathy (DR). However, diabetic macular edema (DME) caused by DR blood-retinal barrier damage is less sensitive to anti-VEGF drugs.Therefore, it is necessary to find supplementary drugs or alternative drugs that can effectively protect the structure of the blood vessel wall. Melatonin is a hormone mainly secreted by the pineal gland, which can play a number of functions in the human body such as regulating biological rhythms, scavenging free radicals, and anti-inflammatory. In recent years, studies have shown that melatonin can improve neuronal degeneration and protect blood vessel structure through multiple mechanisms in retinopathy. In terms of its protective effect on the retinal capillary structure, melatonin can improve the damage of early DR endothelial cells and pericytes through anti-oxidative stress, anti-inflammatory, and inhibiting cell apoptosis so as to protect the integrity of the blood-retinal barrier structure. It suggests that melatonin may provide new ideas for the prevention and treatment of DR, especially with DME.