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Neurovascular unit and diabetic retinopathy

International Eye Science.2023;23(3):353-355. doi:10.3980/j.issn.1672-5123.2023.3.01

The concept of neurovascular unit(NVU), formalized in 2001 at a stroke conference, emphasizes the intimate relationship between the brain and its vessels, i.e., symbiotic relationship between brain cells and cerebral blood vessels in the developmental, structural and functional interdependence. The retina is a piece of brain. Several researchers have introduced the concept of NVU to the retina since 2007. The NVU in the retina includes neurons, glial cells, microvascular endothelial cells and pericytes. Dysfunctional NVU plays a critical role in diabetic retinopathy(DR). The current limited treatments for DR focus on the late-stage complications, i.e., diabetic macular edema and proliferative DR. While the further study on retinal NVU will develop efficacious therapeutic options for the early and all stages of DR.

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Prevalence and risk factors of dry eye patients with corneal epithelial defects: A hospital-based retrospective study

Yi-Ning GUO ; Xiao-Dan JIANG ; Yin-Hao WANG ; Yue-Xin WANG ; Hao YUAN ; Xue-Min LI

International Eye Science.2023;23(3):356-362. doi:10.3980/j.issn.1672-5123.2023.3.02

AIM: To analyze the characteristics and correlated risk factors of dry eye patients with corneal epithelial defects.METHODS: Outpatient medical records of dry eye patients with corneal epithelial defects at Peking University Third Hospital from July 2018 to June 2019 were retrospectively analyzed. The patients' data including sex, age, visit date, presence of comorbidities, and meteorological indicators at the same period were statistically analyzed.RESULTS: A total of 291 dry eye patients with corneal epithelial defects, of whom 75.3% were female, were retrospectively analyzed. Young patients aged 21-30 made up the most(26.5%), while the proportion of teenagers(<18 years, 5.8%)and the elderly(≥61 years, 17.2%)was low. However, as the largest proportion of this population, young and middle-aged patients tend to experience fewer visits(5.4±12.4). Spring and winter were the main seasons of complaints. The meteorological indicators at the same period including fine-particulate matter with a median aerometric diameter of less than 10μm(PM10), sulfur dioxide(SO2), nitrogen dioxide(NO2), and reduced average relative humidity were found significantly correlated with dry eye corneal epithelial defects(P<0.05). Conjunctivitis, cataracts, blurred vision, and trichiasis ranked the top four comorbidities.CONCLUSION: Dry eye corneal epithelial defects of young and female population cannot be ignored. PM10, SO2, NO2, and reduced humidity are found significantly correlated with dry eye corneal epithelial defects. For dry eye patients with conjunctivitis, cataracts, blurred vision, and trichiasis, more attention should be paid to their corneal conditions.

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Vascularization of intravitreal injection of Conbercept in the treatment of retinopathy of prematurity

Zheng FU ; Wei-Wei XIONG ; Xue YIN ; Zhi-Bin HONG ; Xiu-Ting LI ; Xi-Xiang WEI ; Wei-Fang FANG ; Ya-Juan CHEN ; Jing-Wei LIN ; Yan-Hui ZHU ; Yi-Hua ZHU ; Hui YANG

International Eye Science.2023;23(3):363-368. doi:10.3980/j.issn.1672-5123.2023.3.03

AIM: To evaluate retinal vascularization caused by the intravitreal injection of Conbercept in the treatment of a series of retinopathy of prematurity(ROP)cases in Type Ⅰ(threshold and pre-threshold period)and aggressive ROP(A-ROP).METHODS: The data of 34 ROP cases(67 eyes)treated by intravitreal injection of Conbercept(IVC)in the ophthalmology department of the Xiamen Children's Hospital from July 2017 to March 2020 were retrospectively analyzed. Reactivation, which refers to recurrence of acute phase features, occurred at any stage of the disease in the presence or absence of other diseases. RESULT: The average gestational age of the 34 children was 28.82±2.32wk. The average birth weight was 1155.18±398.22g. The lesion zone of 19 cases(37 eyes)was Zone Ⅰ. In 10 cases(20 eyes), the lesion was in Zone Ⅱ, and in 5 cases(10 eyes), the lesion was in the posterior Zone Ⅱ. The total effective rate of disease control in ROP children treated with once IVC was 73.1%(49/67), and the vascularization of Zone Ⅱ was completed. The patients showed variable changes in the vascularization in Zone Ⅲ. For the patients who received one treatment and did not reactivate, the average rate of Type Ⅰ vascularization of ROP was 9.11±2.49wk, and the A-ROP was 13.40±4.04wk. The rate of A-ROP vascularization in Zone Ⅱ was significantly longer compared to Type Ⅰ.CONCLUSION: IVC effectively completes vascularization in Zone Ⅱ.

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Expression pattern of MMP-12 in long-term optic nerve regeneration induced by lens injury

Guo-Dong WANG ; Jian-Feng ZHAO ; Xing-Yu XU ; Xiang-Lin XIANG ; Yi-Wei SHEN ; Zi-Han HE ; Kang LIU ; Yu GENG

International Eye Science.2023;23(3):369-374. doi:10.3980/j.issn.1672-5123.2023.3.04

AIM: To investigate the expression changes of MMP-12 during the long-term axon regeneration induced by the lens injury after the optic nerve clamp trauma in sprague-dawley(SD)rats.METHODS: The optic nerve injury model and lens injury model of SD rats were established, and the 24 experimental animals were divided into control group; lens injury group; optic nerve injury group; lens injury combined with optic nerve injury group, with 6 rats in each group. Reference transcriptome sequencing was used to analyze the expression changes of differentially expressed genes in the injured optic nerve region, and relevant differentially expressed genes with high expression were screened. Quantitative real-time polymerase chain reaction(qRT-PCR)and enzyme-linked immunosorbent assay(ELISA)were used to quantify the expression changes of matrix metalloproteinase-12(MMP-12)in the injured optic nerve region.RESULTS: The Principal Component Analysis of transcriptome sequencing indicated that lens injury combined with optic nerve injury was the principal component of gene expression change. Analysis of gene expression differences showed that the expression of MMP-12 gene was up-regulated in the lens injury combined with optic nerve injury group. The mRNA expression level of MMP-12 in the lens injury combined optic nerve injury group was up-regulated compared with the control group, the optic nerve injury group and the lens injury group at 14d and 21d after successful modeling(P<0.05). At 7, 28d, there was no difference in expression among all groups. The protein expression level of MMP-12 in the lens injury combined with optic nerve injury group was up-regulated compared with the control group and optic nerve injury group at 7, 14 and 21d after successful modeling(P<0.05), and it was up-regulated in the lens injury group combined with optic nerve injury group compared with optic nerve injury group at 21d(P<0.05). At 28d, there was no difference in expression among all groups.CONCLUSION: The up-regulated expression of MMP-12 may be involved in the long-term regeneration of the optic nerve after lens injury.

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Effects of soluble glycoprotein 130 on expression of p-STAT3 and vascular endothelial growth factor-A in retina of mice with diabetes mellitus

Guang-Hui LIU ; Chang-Xuan SHI ; Ya-Jun HONG ; Yong-Zheng ZHENG ; Hang WANG ; Chun MENG

International Eye Science.2023;23(3):375-378. doi:10.3980/j.issn.1672-5123.2023.3.05

AIM: To observe the effect of soluble glycoprotein 130(sgp130)on expression of p-STAT3 and vascular endothelial growth factor(VEGF)-A in retina of mice with diabetes mellitus(DM), and explore the possibility of sgp130 in interfering with inflammatory damage of diabetic retinopathy(DR).METHODS: A total of 45 mice were randomly divided into normal group, DM group and sgp130 group. DM models were made in DM group and sgp130 group with streptozotocin. No special intervention was given to normal group and DM group, but sgp130 group was given intravitreal injection of 1.5mg/mL sgp130 2μL at the 1 and 5wk. After 10wk, all the mice were sacrificed to assess the protein expression of interleukin 6(IL-6), p-STAT3 and VEGF-A in the retina.RESULTS: The expressions of IL-6, p-STAT3 and VEGF-A in retina of DM group were higher than those of normal group at 10wk(all P<0.01). The expression of p-STAT3 and VEGF-A in sgp130 group were lower than those in DM group(all P<0.01).CONCLUSION: The sgp130 can selectively antagonize the trans signal transduction pathway of IL-6, down-regulate the expression of downstream inflammatory factors VEGF-A, and it may be used in the intervention of retinal inflammatory damage related with IL-6 in DM.

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Experimental study of curcumol inhibiting vascular endothelial growth factor-induced neovascularization

Yu-Meng HAO ; Cai-Xia WANG ; Jing-Xue MA ; Xue-Jing LI ; Qing-Li SHANG

International Eye Science.2023;23(3):379-384. doi:10.3980/j.issn.1672-5123.2023.3.06

AIM: To study the role and mechanism of curcumol in neovascularization induced by vascular endothelial growth factor(VEGF).METHODS: Human umbilical vein endothelial cells were cultured in vitro and treated with 50ng/mL VEGF and curcumol at different concentrations. Cell proliferation was detected by CCK-8 and EdU assay, the migration ability of cells was analyzed by Transwell assay, the angiogenesis ability of endothelial cells was analyzed by tube formation assay, and the change of Akt/mTORC1 signal pathway was detected by Western blot.RESULTS: CCK-8 results showed that the OD450 value of cells in 400 and 800 μmol/L curcumol+VEGF group was significantly lower than that in VEGF group(all P<0.01). EdU results showed that the rate of cell proliferation in 400 μmol/L curcumol+VEGF group was significantly lower than that in VEGF group(P<0.001). Transwell assay and the formation assay results showed that the number of migratory cells in 400 μmol/L curcumol+VEGF group was decreased, and the number and length of tube branches were also reduced compared with VEGF group(all P<0.001). Western blot results showed that curcumol significantly inhibited the expression of p-Akt and p-S6, which were downstream targets of Akt/mTORC1 pathway in cells.CONCLUSION: Curcumol can inhibit VEGF-induced cell proliferation, migration and tube formation of vein endothelial cells, and has a strong inhibitory effect on angiogenesis, which can be further studied in the treatment of ocular fundus neovascularization.

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Refractive outcomes after intrascleral fixation of posterior intraocular lens

Fei YANG ; Ming-Wu LI

International Eye Science.2023;23(3):385-389. doi:10.3980/j.issn.1672-5123.2023.3.07

AIM: To evaluate the refractive outcomes after intrascleral fixation of posterior intraocular lens(IOL).METHODS: Retrospective clinical study. A total of 55 patients(55 eyes)who had undergone intrascleral fixation of posterior IOL in Peking University International Hospital from March 2017 to December 2021 were enrolled. Patients were assigned to conventional group(35 eyes)and modified group(20 eyes)according to different surgical procedures. IOL Master combined with SRK/T formula were applied to calculate the diopter of IOL and the residual refractive power, as well as acquiring preoperative values of corneal astigmatism. Optometry, IOL Master and Pentacam were performed 1 and 3mo postoperatively to obtain the postoperative corneal astigmatism, total ocular astigmatism and spherical equivalent which was calculated as the actual diopter. The Image-pro plus analyzer was used to measure the values of IOL tilt and decentration.RESULTS: The 55 eyes that underwent intrascleral fixation of posterior IOL presented hyperopic shift in refraction after operation and the refractive error was 0.75±0.63D at 3mo postoperatively. There was significant difference between the actual diopter and the residual diopter at 3mo after operation(t=2.553, P=0.011). Both conventional group and modified group showed hyperopic shift postoperatively. The refractive error at 1 and 3mo after operation were 0.80±0.43 and 0.84±0.46D in the conventional group and 0.43±0.39 and 0.47±0.26D in the modified group respectively, with significant differences between two groups(1mo: t=3.500, P=0.001; 3mo: t=3.311, P=0.002). There was no significant difference in corneal astigmatism between two groups both at 1 and 3mo postoperatively(all P<0.05). Total ocular astigmatism in the modified group was significantly lower than that in the conventional group(1mo: t=3.884, P<0.001; 3mo: t=3.314, P=0.002). In addition, IOL tilt and decentration in the modified group were significantly less than that in the conventional group at 1 and 3mo postoperatively(all P<0.05). No significant difference was found in IOL tilt and decentration for intra-group comparison at 1 and 3mo postoperatively(P<0.05). Complications of 55 eyes included 2 eyes of transient intraocular pressure elevation, 2 eyes of transient hypotony which recovered after topical medication and 1 eye of vitreous hemorrhage which resolved spontaneously.CONCLUSION: Intrascleral fixation of posterior IOL is proved to be a safe and effective surgical technique, with hyperopic shift easily present after operation. Increasing the refractive power of IOL and targeting mild myopia during IOL power calculation can prevent postoperative hyperopia, but long-term outcomes still need further observation.

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Comparison of visual quality after refractive surgery between smart pulse technology-assisted transepithelial photorefractive keratectomy of 1 050Hz ablation frequency and small incision lenticule extraction

Zheng YUAN ; Chun-Yang ZHOU ; Yue-Hua ZHOU ; Yu LI

International Eye Science.2023;23(3):390-394. doi:10.3980/j.issn.1672-5123.2023.3.08

AIM: To compare the visual quality between smart pulse technology-assisted(SPT)transepithelial photorefractive keratectomy(TransPRK)of 1 050Hz ablation frequency and small incision lenticule extraction(SMILE)for myopia and astigmatism.METHODS: A total of 138 cases(248 eyes)who received corneal refractive surgery in the Eye Hospital of Chengdu University of TCM were enrolled from July 2020 to January 2021. The patients were divided into TransPRK group(64 cases, 123 eyes)and SMILE group(74 cases, 125 eyes)according to the surgical method. The follow-up duration was 6mo. Strehl ratio(SR)and high-order aberration at 6mm pupil diameter measured by Sirius anterior segment integrated analyzer and LogMAR visual acuity were recorded at different preoperative and postoperative time points.RESULTS: The uncorrected visual acuity(UCVA)of TransPRK group was worse than SMILE group at 1wk and 1mo after surgery(all P<0.05), but UCVA was better in TransPRK group at 6mo after surgery(P<0.05). SR in TransPRK group was lower than that in SMILE group at 1wk and 1mo after surgery(all P<0.05). There was no significant difference in SR between the two groups at 3 and 6mo after surgery(P=0.968, 0.433). At 1wk after surgery, there was no significant difference in coma between the two groups(P=0.554). At 1, 3, and 6mo after surgery, coma in the TransPRK group was lower than that in SMILE group(all P<0.05). At 1wk, 1 and 3mo after surgery, the trefoil aberration in TransPRK group was higher than that in SMILE group(all P<0.05). At 6mo after surgery, there was no significant difference in trefoil aberration between the two groups(P=0.167). At 6mo after surgery, UCVA of TransPRK group and SMILE group were -0.13±0.05 and -0.11±0.08, respectively, which were better than the best corrected visual acuity(BCVA)before surgery(-0.07±0.05 and -0.07±0.05; all P<0.05). Furthermore, the SR of both groups was higher than that before surgery(all P<0.05).CONCLUSION: Both SPT-assisted TransPRK of 1 050Hz ablation frequency and SMILE can achieve better visual acuity after refractive surgery, while SMILE has better visual quality at 1wk and 1mo after surgery. However, SPT-assisted TransPRK of 1 050Hz ablation frequency has better visual acuity at 6mo after surgery than SMILE, and the coma is smaller.

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Advances in the diagnosis and treatment of retinal artery macroaneurysms

Jia CHEN ; Yu-Ling ZOU

International Eye Science.2023;23(3):395-399. doi:10.3980/j.issn.1672-5123.2023.3.09

Retinal arterial macroaneurysm(RAM)is a kind of acquired retinal vascular disorder. The pathogenesis of RAM is not yet clear, and it is associated with some systemic conditions, including hypertension, arteriosclerosis and hyperlipidemia. RAM is prone to exudation or bleeding, leading to some other complications in the condition of hypertension due to the weak tube wall, and its clinical manifestations are complex and diverse, which makes it difficult to diagnose. RAM itself has a tendency of self-degeneration, and the prognosis of visual acuity is good if the lesion doesn't involve the macular area. However, when the macula is affected by exudation and/or bleeding, the vision is severely affected and some feasible treatments are needed. Understanding the typical imaging manifestations of RAM is helpful to make a definite diagnosis and give corresponding treatment measures. In this paper, the manifestations of RAM by various examination methods are reviewed and the corresponding treatments of different types of RAM are summarized, aiming to provide reference for the early diagnosis and treatment of RAM in the future.

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Application and prospect of gene therapy for fundus vascular diseases

Chao-Yang ZHANG ; Jing-Xiang ZHANG ; Jing-Fa ZHANG

International Eye Science.2023;23(3):400-406. doi:10.3980/j.issn.1672-5123.2023.3.10

Fundus vascular diseases, including neovascular age-related macular degeneration(nAMD)and diabetic retinopathy(DR), are the leading causes of visual impairment worldwide. With the accelerated aging and increased incidence of diabetes, the prevalence of these two fundus diseases will continue to rise. Currently, intraocular injection of anti-vascular endothelial growth factor(anti-VEGF)remains the first-line treatment for fundus vascular diseases, but disadvantages exist, such as frequent intraocular injections, high cost and poor compliance, thus more durable and effective therapeutic strategies need to be explored. The successful application of gene therapy in inherited retinal diseases(IRDs)provides a new idea for the treatment of fundus vascular diseases. With the ongoing of several clinical trials, gene therapy for fundus vascular diseases is expected to be employed in the clinical setting. But there still remain some concerns, including the optimal therapeutic targets selection, administration route and safety issues. This review focuses on the application and prospect of gene augmentation and gene editing-mediated anti-VEGF therapy for the treatment of nAMD and DR.

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