Professor Shao Yi: New Progress in Dry Eye Research - Brain Clues

Editor's note: Dry eye is a chronic ocular surface disease characterized by abnormalities of tear fluid and tear film, accompanied by inflammation, tissue damage, neurological abnormalities, and visual disturbances. The prevalence of dry eye ranges from 5% to 50%, and can be as high as 75% in adults over the age of 40. The etiology of dry eye is complex, and its pathogenic mechanism has not been fully elucidated. Common risk factors include advanced age, female, low humidity environment and autoimmune diseases. So why do patients with dry eye, especially those with functional dry eye, experience symptoms such as visual impairment, neuropathic pain, anxiety, and depression? Studies have shown that 25% of patients with depression and eye disease are dry eye patients. Inflammation is an important factor leading to dry eye. Sympathetic and parasympathetic nerves jointly participate in the regulation of tear secretion through this neural reflex loop; tear hypertonicity can significantly reduce the sensitivity of corneal nerves, and nerve dysfunction can lead to abnormal tear secretion, and ultimately the ocular surface. The homeostasis is unbalanced, and the inflammatory response activates the glia in the brain to induce the expression of pro-inflammatory cytokines, and induces the sensitization of the central nervous system to pain through signal amplification; after tear hyperosmolarity causes ocular surface tissue damage, the ocular surface immune system is activated, The lacrimal gland and conjunctival tissue of most patients with dry eye have a large number of lymphocytic infiltrates. Intracerebral glial activation induced by dry eye inflammatory response induces the expression of pro-inflammatory cytokines and induces central sensitization to pain. These series of reactions lead to long-term ocular surface homeostasis and chronic neuropathic pain in patients with dry eye. Sustained activation and involvement of the cornea-trigeminal-brain stem nerve pathway affects corneal pain conduction, and long-term neuropathic ocular pain in patients with dry eye may appear "central facilitation". Due to the unknown mechanism of dry eye, at the 2022 Vision China International Forum on Vision Health Innovation and Development, Professor Shao Yi from the First Affiliated Hospital of Nanchang University shared a wonderful report entitled "Brain Clues of Dry Eye". Research shows: changes in brain image fMRI of patients with dry eye Prof. Shao pointed out that according to the research results, the ReHo values ​​of the middle frontal gyrus, inferior frontal gyrus and superior frontal gyrus of dry eye patients are significantly reduced. ALFF in patients with dry eye decreased in right middle frontal gyrus (MFG)/right inferior orbitofrontal cortex (OFC), left deltoid inferior frontal gyrus, left MFG, and right superior frontal gyrus, in the left cerebellum Increase. DTI showed that patients with dry eye had lower FA values ​​in the left superior longitudinal tract (LSLF), right superior longitudinal tract (NODDI), and corpus callosum (CC), but higher MD values ​​in the LSLF, right hindlimb of internal capsule, and right hindlimb. The fALFF value of the left calcarine sulcus (CS) in the dry eye patients was significantly higher than that of the HC group, while the fALFF values ​​of the bilateral middle frontal gyrus (MFG) and right MFG/right inferior frontal gyrus (IFG) were significantly lower than those of the HC group. Group. Among them, the dry eye pain score was negatively correlated with the ACC brain area value. Based on voxel morphology analysis (VBM), it was found that dry eye patients in menopausal women had significantly decreased VBM in Putamen_L, while VBM in thalamus_R, precuneus_L, frontal_Sup_R, midbrain wing and frontal_L significantly decreased. VBM increased in Temporal_Sup_R, Anterior Central_R and Insula_L. Repetitive transcranial magnetic stimulation (rTMS) improves anxiety, depression, visual impairment, and pain in severe dry eye. By stimulating the emotional center, pain center and visual center, etc., it can effectively improve the symptoms of anxiety, depression and pain in patients with severe dry eye. Results of the study: Three brain regions were involved in patients with dry eye. The study found that patients with dry eye mainly had three brain regions involved: 1. The occipital lobe is an important area for visual regulation in the brain, located above and below the calcarine sulcus and above the calcarine sulcus. The upper and lower retinas receive impulses from the upper and lower retinas, respectively, and the upper and lower thirds of the posterior and inferior calcarine sulcus receive impulses from the macula. Patients with abnormal occipital discharge may experience hallucinations, episodic amaurosis, abnormal eye movements, and visual field defects. Abnormal functional connectivity in primary visual cortex regions has been previously found in studies of anisometropic amblyopia, strabismus, and glaucoma. The study found that the fALFF value of the left calcarine sulcus in patients with dry eye increased significantly, which indicated that the activity of this brain region in patients with dry eye was enhanced. It is believed that the increase of fALFF value in the visual cortex of the calcarine sulcus may compensate for the visual impairment caused by dry eye. 2. The middle frontal gyrus (MFG) is located above the front of the brain and is not only responsible for language processing, but also related to stress response, cognitive function, and attention control. MFG is involved in the regulation of descending pain perception, and dysfunction of descending circuits can lead to pain, and reduced gray matter mentions of MFG were found in patients with cluster headache. The fALFF values ​​of bilateral MFG in patients with dry eye were significantly lower, suggesting that patients have dysfunction in this area. Therefore, it is speculated that MFG dysfunction may be related to clinical symptoms such as ocular pain, anxiety and depression in patients with dry eye. 3. The inferior frontal gyrus (IFG) is closely related to the regulation of emotion and attention, and it is also involved in the protection of memory. In children with autism spectrum disorder, lack of sleep shows increased negative emotions, decreased positive emotions and psychomotor abilities, and brain Functional finding of reduced connectivity between the IFG and the thalamus. The fALFF value of IFG in patients with dry eye was significantly lower, which may be related to the negative emotions caused by visual impairment and long-term ocular discomfort in patients with dry eye. Cognitive deficits in patients with depression are associated with primary visual cortex function at the calcarine sulcus. The gray matter volume in the MFG, IFG, middle temporal gyrus and other regions was significantly reduced in patients with severe depression. The use of antidepressants can increase the risk of dry eye, and patients with dry eye with a longer duration will experience a vicious cycle of symptoms such as eye discomfort, chronic neuropathic pain, visual disturbances, and sensory disturbances. The fALFF value near the calcarine sulcus in patients with dry eye was significantly higher than that in the HC group, while the fALFF values ​​of MFG and IFG were significantly lower than those in the HC group, suggesting that a series of manifestations such as visual impairment caused by brain dysfunction in patients with dry eye are related to anxiety and depression. Neuropathophysiological mechanisms. Professor Shao concluded that the pathogenesis of dry eye is complex, the clinical manifestations are diverse, and the brain function also shows abnormal changes to varying degrees, and the current treatment methods are limited. This study is the first to use resting-state magnetic resonance imaging combined with machine learning technology to find specific markers of brain molecular imaging, early diagnosis of dry eye patients, and use of repetitive transcranial magnetic stimulation (rTMS) and repetitive transcranial direct current stimulation to treat dry eye. . It is hoped that in the future, a more effective, convenient and comprehensive dry eye prevention and treatment strategy can be provided through local therapy on the ocular surface combined with the recovery of brain function. Expert Profile Prof. Shao Yi, MD, Chief Physician, Doctoral Supervisor, Postdoctoral Supervisor, Deputy Director of the Department of Ophthalmology of the First Affiliated Hospital of Nanchang University, Provincial Jinggang Scholar, Ganjiang Scholar, and Visiting Scholar of Bascom Palmer Eye Hospital in the United States. At present, he is a member of ARVO in the United States, a member of AAO in the United States, a member of EVER in Europe, the chairman of ophthalmic imaging and intelligent medical treatment of China Medical Education Association, the chairman of the Corneal Disease and Ocular Surface Disease Committee of China Population Culture Promotion Association, the Returnee Physician Association and China Microcirculation. Deputy Director of the Association's Translational Medicine Youth Committee, Standing Committee Member of Intelligent Ophthalmology of China Medical Education Association, Member of Asian Dry Eye Association, Youth Member of Ophthalmology Branch of Chinese Medical Doctor Association, Member of Pathology Group, Member of Eye Care of China Association of Traditional Chinese Medicine, Jiangxi Youth Association Vice President and Chairman of the Clinical Medicine Special Committee, Standing Committee Member of the Provincial Federation of Scientific and Technological Innovation Talents, Standing Committee Member of the Provincial Medical Science Management Society, Head of the Dry Eye and Ocular Surface Diseases Group of the Provincial Medical Doctor Association, and the Provincial Integrative Medicine Association Corneal Disease Group long. He has published more than 290 international SCI papers (250 first/newsletter papers, cited more than 8,000 times), more than 280 core papers of Peking University, and 24 reviews. Presided over 36 national-level projects (5 projects), provincial key R&D (major) projects (4 projects), and provincial natural (key) projects (5 projects), delivered more than 30 speeches at international conferences such as ARVO and WOC, and obtained national patents 24 items, edited 38 ophthalmology books (15 Chinese, 14 English translations, 9 popular science), participated in the compilation of 6 Ministry of Health textbooks, 2 national standards, 3 national guidelines, and 12 expert consensus. The first person to finish won the American Ophthalmology and Vision Science Award, the first prize of Invention, Entrepreneurship and Innovation Award of China Invention Association, the second prize of Science and Technology Award of China Medical Education Association (2 times), the second and third prizes of provincial scientific and technological progress, and the second prize of provincial medical science and technology. , the third prize, the first provincial excellent science popularization work award, the provincial first excellent science popularization creation award and so on 15 times.