Immune checkpoint inhibitors (ICIs) are novel immunotherapy-based drugs that have become increasingly popular in the treatment of lung cancer. Researchers have recognized ocular immune-related adverse events (irAEs) secondary to ICIs because of their vision-threatening characteristics. However, they are incompletely characterized and no studies have reported the ICI-related ocular irAEs in lung cancer. Therefore, we aimed to comprehensively illustrate the clinical characteristics, contributory factors, diagnosis, and management of ICI-related ocular irAEs in lung cancer, based on previously reported 79 patients. Ophthalmoplegia (40.51%), uveitis (20.25%), and dry eye (17.72%) were the most common ICI-related ocular irAEs in lung cancer. Ptosis was the most common (36.71%) and the highest mortality (23.33%) of ophthalmoplegia. Patients in Asia and patients who underwent combination therapy with programmed cell death-1 and cytotoxic T-lymphocyte-associated antigen 4 inhibitors demonstrated significantly higher frequency of ophthalmoplegia than other ocular irAEs. Most ICI-related ophthalmoplegia and uveitis in lung cancer were observed in the first 10 weeks following the initiation of ICIs. Furthermore, the onset time of dry eye and other ocular irAEs was much longer. In addition, 92.31% of the patients with ocular irAEs other than ophthalmoplegia could be remised. In conclusion, ocular irAEs secondary to ICIs in lung cancer are non-negligible, particularly ophthalmoplegia. Ethnicity and the type of ICIs play important roles in the distribution of ocular irAEs. ICI-related ophthalmoplegia in lung cancer presented with early onset and worse prognosis features, thus necessitating further attention.
Glaucoma as the leading neurodegenerative disease leads to blindness in 3.6 million people aged 50 years and older worldwide. For many decades, glaucoma therapy has primarily focused on controlling intraocular pressure (IOP) and sound evidence supports its role in delaying the progress of retinal ganglial cell (RGC) damage and protecting patients from vision loss. Meanwhile, accumulating data point to the immune-mediated attack of the neural retina as the underlying pathological process behind glaucoma that may come independent of raised IOP. Recently, some scholars have suggested autoimmune aspects in glaucoma, with autoreactive T cells mediating the chief pathogenic process. This autoimmune process, as well as the pathological features of glaucoma, largely overlaps with other neurodegenerative diseases in the central nervous system (CNS), including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. In addition, immune modulation therapy, which is regarded as a potential solution for glaucoma, has been boosted in trials in some CNS neurodegenerative diseases. Thus, novel insights into the T cell-mediated immunity and treatment in CNS neurodegenerative diseases may serve as valuable inspirations for ophthalmologists. This review focuses on the role of T cell-mediated immunity in the pathogenesis of glaucoma and discusses potential applications of relevant findings of CNS neurodegenerative diseases in future glaucoma research.
Glaucoma is the main cause of irreversible visual loss worldwide, and comprises a group of progressive, age-related, and chronic optic neuropathies. Prostaglandin analogs are considered a first-line treatment in the management of glaucoma and have the best efficacy in reducing intraocular pressure. When comparing these therapeutic agents between them, long-term therapy with 0.03% bimatoprost is the most effective followed by treatment with 0.005% latanoprost and 0.004% travoprost. The prevalence of adverse events is lower for latanoprost than for other prostaglandin analogs. However, some patients do not respond to the treatment with prostaglandin analogs (non-responders). Intraocular pressure-lowering efficacy differs significantly between individuals partly owing to genetic factors. Rs1045642 in ABCB1, rs4241366 in SLCO2A1, rs9503012 in GMDS, rs10306114 in PTGS1, rs11568658 in MRP4, rs10786455 and rs6686438 in PTGFR were reported to be positive with the response to prostaglandin analogs in patients with glaucoma. A negative association was found between single nucleotide polymorphisms of PTGFR (rs11578155 and rs6672484) and the response to prostaglandin analogs in patients with glaucoma. The current review is an analysis of the information relevant to prostaglandin analog treatments based on previous literatures. It describes in detail the clinical pharmacology and pharmacogenetics of drugs belonging to this therapeutical class to provide a sound pharmacological basis for their proper use in ophthalmological clinical practice.
Purpose: To compare the prevalence of computer vision syndrome in university students of different teaching modes during the SARS-CoV-2 outbreak period.Methods: A cross-sectional survey study using the validated Computer Vision Syndrome Questionnaire in Chinese medical students of Sichuan University who took classroom lectures and the same-grade foreign students from a Bachelor of Medicine and Bachelor of Surgery (MBBS) program who took online lectures with similar schedules.Results: A total of 137 responses from 63 Chinese students and 74 MBBS students were obtained. The highest frequency of digital screen time was 7-9 h (43.24%, 32/74) for MBBS students and 2-4 h (46.03%, 29/63) for Chinese students. The prevalence of computer vision syndrome among Chinese students and MBBS students were 50.79% and 74.32%, respectively (P = 0.004). The average numbers of reported symptoms were 5.00 ± 2.17 in Chinese students and 5.91 ± 1.90 in MBBS students (P = 0.01). The three most highly reported symptoms were “heavy eyelids” (53.97%), “dryness” (50.79%), and “feeling of a foreign body” (46.03%) in Chinese students and “dryness” (72.97%), “feeling of a foreign body” (62.16%), and “heavy eyelids” (58.11%) in MBBS students. The sum grades of computer vision syndrome had a moderate positive correlation with screen time (Spearman's correlation coefficient = 0.386, P < 0.001). The grades of symptoms of “feeling of a foreign body,” “heavy eyelids,” and “dryness” showed a weak positive correlation with screen time (Spearman's correlation coefficients were 0.220, 0.205, and 0.230, respectively).Conclusion: Online study may contribute to the prevalence of computer vision syndrome among university students.
To evaluate the reliability of β-III-Tubulin protein as a retinal ganglion cell (RGC) marker in the experimental glaucoma model. Glaucoma mouse models were established by injecting polystyrene microbeads into the anterior chamber of C57BL/6J mice, then their retinas were obtained 14d and 28d after the intraocular pressure (IOP) was elevated. Retinal flat mounts and sections were double-labeled by fluorogold (FG) and β-III-Tubulin antibody or single-labeled by β-III-Tubulin antibody, then RGCs were counted and compared respectively. IOP of the injected eyes were elevated significantly and reached the peak at 22.8±0.7 mm Hg by day 14 after injection, then dropped to 11.3±0.7 mm Hg by day 28. RGC numbers counted by FG labeling and β-III-Tubulin antibody labeling were 64 807±4930 and 64614±5054 respectively in the control group, with no significant difference. By day 14, RGCs in the experimental group decreased significantly compared to the control group, but there was no significant difference between the FG labeling counting and the β-III-Tubulin antibody labeling counting either in the experimental group or in the control group. The result was similar by day 28, with further RGC loss. Our result suggested that the β-III-Tubulin protein was not affected by IOP elevation and can be used as a reliable marker for RGC in experimental models of glaucoma.
28 June 2021 in Frontiers in Cellular Neuroscience
Retinal organoids (ROs), which are derived from stem cells, can automatically form three-dimensional laminar structures that include all cell types and the ultrastructure of the retina. Therefore, they are highly similar to the retinal structure in the human body. The development of organoids has been a great technological breakthrough in the fields of transplantation therapy and disease modeling. However, the translation of RO applications into medical practice still has various deficiencies at the current stage, including the long culture process, insufficient yield, and great heterogeneity among ROs produced under different conditions. Nevertheless, many technological breakthroughs have been made in transplanting ROs for treatment of diseases such as retinal degeneration. This review discusses recent advances in the development of ROs, improvements of the culture protocol, and the latest developments in RO replacement therapy techniques.