The diagnosis and treatment of age-related macular degeneration (AMD) is an international hotspot of eye research. Successful clinical applications of antiVEGF drugs promoted both basic research and clinical practice of AMD. A number of countries and professional societies have established clinical guidelines for AMD management, including the epidemiology, risk factors, diagnosis, classification, and treatment process. These AMD guidelines are mostly based on recently published results of clinical trials, provided good model of evidence based medicine. It is urgent and necessary to have our own guideline which is suitable for Chinese patients. Reviewing and learning existed guidelines will help us to improve the clinical practice of AMD in China.
Using optical imaging equipment with different wavelength and computer technology, fundus optical imaging diagnostic techniques can record fundus reflected light, auto fluorescence and emitted light after excitation by external light source in order to observe and analyze the structure and pathological process of retina and choroid. Advances in fundus optical image capture technology (including laser, confocal laser, spontaneous auto-fluorescence, multispectral imaging) and storage and analysis technology, promote this field into a high-definition digital imaging era, with features of rapid, non-invasive, wide-angle three-dimensional multi-level integration, dynamic automatic navigation location tracking and combined application of a variety of optical imaging diagnostic techniques. In order to promote clinical and scientific research of ocular fundus diseases, we need to understand the development trend of optical imaging diagnostic technique, interpret the fundus imaging features appropriately, reasonably chose different inspection techniques, establish standardized diagnosis criteria and continue to expand clinical applications.
Macrophages are major effecter cells of nonspecific immune response, the polarization of which plays a great role in inflammation, repairing and angiogenesis. According to functional phenotypes, macrophages can be polarized to classically activated type (M1), which could promote angiogenesis, and alternatively activated type (M2), which could inhibit angiogenesis. The proportion of M1/M2 could modulate the growth of choroidal neovascularization (CNV). Under the conditions of aging and injury within the retina, macrophages may polarize to M2, which could generate several proangiogenic factors, initiating and promoting the formation of angiogenesis and fibrous scar. Therefore, regulation of macrophage polarization is expected to inhibit angiogenesis and provide new insight for treatment of CNV.
The reattachment rate, macular hole (MH) closure rate, visual acuity improvement and re-detachment rate of MH retinal detachment (MHRD) of high myopia are not satisfactory owing to long axis oculi, posterior scleral staphyloma and macular atrophy. At present, minimally invasive vitrectomy surgery combined with the internal limiting membrane flap technique has become popular in the treatment of MHRD, as it can promote MH closure, and significantly improve the outcome of MHRD. However if this method can improve the postoperative visual function is still controversial. The advantage of this technique is that the loosened internal limiting membrane is applied to cover the MH surface to form a scaffold structure similar to the basement membrane. It can stimulate Müller cell gliosis more effectively, and promote tissue filling in the MH which results in MH closure. It can also promote retinal reattachment and reduce the likelihood of retinal re-detachment. This technique is expected to be a standard surgical method for the treatment of MHRD of high myopia in the future. The inserted internal limiting membrane flap technique is relatively easy to perform, induces stable flaps by simple procedures, and can be an essential complement procedure of the inverted internal limiting membrane flap technique. In order to reduce the recurrence rate in the future, it is necessary to further define the indications of different surgical methods and the predictive effects of MH healing mode on the success rate and visual function recovery.
Pyroptosis is a newly discovered form of cell death. Through the activation of inflammasome complexes, pyroptosis induces the production of interleukin (IL) -1β and IL-18, and the osmotic swelling of cells, thus induces cellular rupture and death. It plays a role in the pathological process of a variety of human diseases. The death of retinal cells including photoreceptor cells and retinal pigment epithelium (RPE) cells is the main reason leading to visual dysfunction in the pathogenesis in ocular fundus diseases. Researches have demonstrated that pyroptosis is closely related to the onset and progression of various retinal diseases. In age-related macular degeneration, pyroptosis directly causes apoptosis of RPE cells and upregulation of pro-inflammatory factors, enhancing toxic effect of lipofuscin. For retinitis pigmentosa, pyroptosis is the leading manner of death of secondary cone photoreceptor cells. In cytomegalovirus retinitis, pyroptosis is the main responding way to infection. This review presented the molecular mechanism of pyroptosis and its role in age-related macular degeneration, retinitis pigmentosa and cytomegalovirus retinitis and other retinal diseases.
Diabetic retinopathy (DR), which is a common complication of diabetic and the main cause of blindness, brings not only a heavy economic burden to society, but also seriously threatens to the patients’ quality of life. Clinical researches on the therapies of DR are active at present, but how to perform a good clinical research with scientific design should be considered with high priority. The randomized controlled trial (RCT) is considered to be the gold standard for evidence-based medicine, but RCT is not always perfect. Limitations still exist in certain circumstance and the conclusions from RCTs also need to be interpreted by an objective point of view before clinical practice. Real world study (RWS) bridges the gap between RCT and clinical practice, in which the data can be easily collected without much cost, and results might be obtained within a short period. However, RWS is also faced with the challenge of not having standardized data and being susceptible to confounding bias. The standardized single disease database for DR and propensity score matching method can provide a wide range of data sources and avoid of bias for RWS in DR.
Photoreceptor cells are special retinal neurons with photo-transformation ability. Loss of photoreceptors in age-related macular degeneration (AMD) is secondary to RPE loss, leakage of serum components from the neovascularization and scar formation, which is one of the main mechanisms of irreversible visual impairment in patients with AMD. Many studies have shown that inflammatory environment is involved in the process of photoreceptor cell death. Aging, photooxidation injury and other factors affects the retinal microenvironment through different levels of mechanisms such as retinal pigment epithelial cells, retinal glial cells, hematogenous macrophages and inflammatory factors, which results in photoreceptor injuries and participates in the progression of AMD by drusen formation and neovascularization. This study reviews the research status and progress of inflammation and photoreceptor cell death, and provides new ideas for exploring the blinding mechanism and treatment strategies of AMD.
Age-related macular degeneration (AMD) is an age-related degenerative disease with complex pathogenesis, whose initial lesion is accompanied with immune inflammatory response. Amyloid beta (Aβ), a small-molecule protein generated by the hydrolysis of amyloid precursor protein, as the main component, is involved in the formation of drusen, which serves as the early characteristic of AMD. In the local inflammatory response of AMD, Aβ is an important pathological deposit, promoting the proliferation and differentiation of macrophages as well as changing their morphology to accelerate the progression of AMD. In addition, Aβ can also regulate immune molecules and the complement system by activating inflammatory pathways, thus mediating chronic retinal inflammation and promoting the course of AMD. However, since AMD is not caused by inflammation alone, only the immunosuppression may not be effective in inhibiting the course of AMD, and thus the future development is to rebalance the disordered immune system in AMD patients eyes.
The application of gene therapy in ocular diseases is gradually expanding from mono-gene inherited diseases to multigene, multifactorial, common and chronic diseases. This emerging therapeutic approach is still in the early exploratory stage of treating diseases, and the expected benefits and risks remain highly uncertain. In the delivery process of gene therapy drugs, viral vector is currently one of the most mature and widely used vectors. The occurrence of vector-associated immunity will affect the short-term and long-term effects of gene therapy, and even cause permanent and serious damage to visual function. Therefore, gene therapy vector-associated immunity is the focus and challenge for the safety and long-term efficacy of gene therapy. During the perioperative and follow-up of gene therapy, attention should be paid to the monitoring of vector-associated immune inflammation, and appropriate measures should be taken to deal with the corresponding immune response, so as to achieve the best visual benefits for patients.