Fighting blinding fundus diseases: China on the way!

Abstract

The main causes of blindness have changed in the past decades in China. Through years of unremitting efforts, the once primary cause of blindness, trachoma, is being wiped out in most areas of China, no longer staying a public health problem any more (Jonas et al. 2009). Cataract, another blinding anterior segment disease, is relieved greatly by fast development of microsurgical technique as well as increased rate of cataract surgical coverage in China. With the increase in Chinese life expectancy and climbing prevalence rate of diabetes, ocular fundus diseases have replaced the former ones and gradually become the major threats for visual quality (Wang et al. 2014). Therefore, more responsibilities of preventing blindness are now falling on doctors of fundus diseases. With over 1.3 billion people, preventing those blinding fundus diseases in China is indeed an enormous challenge and the situation now remains serious. Perhaps, the most concerning fundus disease currently in China is age-related macular degeneration (AMD), which causes irreversible blindness in senior people with prevalence still on the rise (Sun et al. 2013; Ye et al. 2014). Genetic studies have been conducted in Chinese patients to gain an insight into the Chinese genetic background associated with AMD. A multicenter case–control study recruiting 535 AMD patients and 469 controls in China reported for the first time that 11 SNPs in complement H (CFH), two in age-related maculopathy susceptibility 2 (ARMS2), and two in high-temperature requirement factor A1 (HTRA1) were strongly associated with Chinese AMD patients (Tian et al. 2012a). Other genetic associations with AMD patients of Chinese descent were also shown in different researches. It is worth mentioning that Tian et al. (2012b) indentified that the response of bevacizumab therapy may be influenced by CFH, ARMS2 and HTRA1 genotypes in the Chinese population. All these work provide valuable information for precision medicine and individualized treatment. Another macular disease, polypoidal choroidal vasculopathy (PCV), is believed by some researchers as one of the specific AMD, while others regard it as an independent fundus disease. However, there is no doubt that PCV presents relatively high incidence in Asian populations and its clinical and prognostic features differ from AMD. In view of this, Chinese ophthalmologists focus on the question whether PCV share the similar mechanism with AMD and whether the therapeutic approaches may vary. An independent Chinese sample bank of PCV was established, and systematic investigations have been initiated to reveal the genetic susceptibility, mechanism, treatment and prognosis of PCV among Chinese patients (Huang et al. 2014; Ye et al. 2016). Another two blinding fundus diseases posing great socio-economic burdens in China are diabetic retinopathy (DR) and retinopathy of prematurity (ROP). The former is the leading cause of vision loss in the middle-aged and elderly in China while the latter accounts for the first cause of blindness in children. Both of them brought huge pressures and challenges to ophthalmologists and government in China. With the ageing population, China is now facing the serious problem of the high prevalence and blindness rate of DR (Xie et al. 2009). Extensive work has been carried out to cope with the situation, including epidemiologic investigation, community screening and evidence-based medicine. Emphasis has been put on the community-based system of prevention and management of DR. Chinese ophthalmologists are committed to build a new comprehensive mode of ‘Health Education – Screening – Referral – Treatment – Follow-up – Health Management’ strategy to fight the disease. In 2014, the new edition of Chinese guideline of diabetic retinopathy was published by the Chinese Ocular Fundus Society and Chinese Ophthalmological Society. It was well designed and combined with China's national conditions to promote the prevention and treatment efforts towards DR. Another landmark in combating fundus diseases in China is the guideline for therapeutic use of oxygen and prevention and treatment of retinopathy in premature infants issued by Ministry of Health of China in 2004. Since the guideline was issued and popularized, regular screening of ROP has been universalized and statistics showed that 99.63% of the infants in China were now covered by the guideline. In 2012, World ROP Congress III was held in Shanghai, China, indicating a certain extent of international recognition of our work. The application of anti-vascular endothelial growth factor (anti-VEGF) drugs is generally acknowledged as a milestone in the treatment of retinal neovascular disorders in the last century. Before that, there is no treatment for neovascularization-related ocular diseases, leaving most of those patients loss of vision eventually. The development of anti-VEGF drugs shed light upon those previously untreatable neovascular fundus diseases. In China, clinical trials have been implemented to verify the safety, efficacy and optimal dosage regimen of the commercial anti-VEGF agents (Li et al. 2012). Now those drugs are clinically used to treat neovascular AMD, diabetic macular oedema (DME), retinal vein obstruction (RVO) and choroidal neovascularization (CNV) in Chinese patients with favourable efficacy. However, considering the high cost and frequency of the therapy and the current realities in China, there is a need for more practical and economical alternatives to treat such a large group of patients in this developing country. Perhaps, the most refreshing news recently from China is the use of conbercept, a novel anti-VEGF drug with China's own independent intellectual property rights (Li et al. 2014). Conbercept is being developed by Chinese Pharmaceutical Enterprises from 2005, and it gained approval from China Food and Drug Administration for the treatment of neovascular AMD in 2014. As a recombinant fusion protein, it could neutralize all VEGF-A isoforms, as well as VEGF-B, and PlGF. The reports from Phase I and Phase II studies of conbercept have already been published, which demonstrated the safety and effectiveness of intravitreal injections of conbercept for the treatment of CNV secondary to AMD (Zhang et al. 2011; Li et al. 2014). Then, the Phase III study, the PHOENIX study, further confirmed the efficacy of the drug, which was reported on American Academy of Ophthalmology Annual Meeting in 2015. As new therapies constantly emerge, independent third-party assessment agencies are needed for more clinical trials. In 2011, under the support of National Science and Technology Major Project of 12th Five-year Plan, the first Chinese clinical evaluation and research centre for new drugs development for fundus disease was established in Shanghai, China. Looking back over the past several decades, progress in prevention of sight-threatening fundus diseases has been made to a certain degree in China, although there is still a long way to go for this populous developing country. However, it is delighted to notice that Chinese ophthalmologists and researchers are making their joint efforts on fighting blinding fundus diseases. In this special issue of Acta Ophthalmologica, studies concerning different areas of fundus diseases conducted by Chinese colleagues were well written and presented.