Morphological and functional retinal changes in neovascular age-related macular degeneration treated with intravitreal bevacizumab

Purpose: This study was conducted to determine the morphological and functional retinal changes in patients with neovascular age?related macular degeneration (nAMD) treated with intravitreal bevacizumab 1.25 mg. Methods: This was a prospective, nonrandomized, interventional study. Eighteen eyes of 18 subjects with nAMD were treated with intravitreal bevacizumab (1.25 mg) injection. Subjects underwent complete ophthalmic evaluation which included visual acuity, slitlamp examination, tonometry, binocular ophthalmoscopy, optical coherence tomography (OCT), and MP1 microperimetry before the intravitreal injection and the follow?up at 1 and 3 months. Test of significance such as Chi?squared test, paired ttest and oneway analysis of variance (ANOVA) linear trend were used to compare the pre? and post?anti?VEGF outcomes. Intraclass correlation was done to assess the intra observer variability. Results: Mean retinal sensitivity had increased from 3.77 ± 3.13 dB at baseline to 4.93 ± 2.42 dB at 3 months (P = 0.05). Visual acuity improved from 0.62 ± 0.36 at baseline to 0.52 ± 0.36 at 1 month and 0.48 ± 0.34 at 3?month followup, but overall change was not significant (P = 0.40). There was a significant reduction in central foveal thickness (CFT) from 274.61 ± 117.95 at baseline to 179.83 ± 84.18 at 1 month and 179.00 ± 126.55 at 3?month follow?up (P = 0.013). Conclusion: Intravitreal bevacizumab (1.25 mg) injection in nAMD improves retinal function, quantified by retinal sensitivity, scotoma characteristics, fixation stability by MP 1 microperimetry and morphological parameters quantified by CFT in SDOCT. These changes show the effectiveness of treatment with intravitreal bevacizumab in nAMD

Comparison of the effects of different intraocular infusion solutions on histology and function of retina / 中华实验眼科杂志

Objective:To compare the effects of different intraocular infusion solutions on histology and function of retina.Methods:Human corneal endothelial cells (HCEC), human retinal pigment epithelium (HRPE) cells and rat retinal ganglion cells (RGC) were divided into normal control group, balanced saline solution (BSS) group and compound electrolyte intraocular irrigating solution (CEIIS) group, and the cells were cultured in 10% DMEM/F12 medium, BSS and CEIIS for 12, 24 and 48 hours, respectively, according to grouping.The proliferation absorbance value of cultured cells was measured by cell counting kit-8 (CCK8) method.The expression of apoptosis related proteins in cultured cells was detected by cellular immunofluorescence staining.The cell apoptosis rate and cell cycle were measured by flow cytometry.The mitochondrial damage was detected by lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) quantitative detection kit.Fifteen New Zealand white rabbits were randomly divided into control group ( n=3), BSS group ( n=6) and CEIIS group ( n=6). The left eyes were taken for vitrectomy and different intraocular perfusion fluids were used during vitrectomy according to grouping.The retinal function of operative eyes was measured by flash electroretinogram (ERG) before operation and 24 hours after operation, and the structural changes of each layer of retina were detected by optical coherence tomography (OCT). The early apoptosis of retinal cells was detected by TUNEL staining.The expressions of cytochrome C and bax protein in retina were detected by immunohistochemical staining.The ultrastructural changes of retina were observed under a transmission electron microscope.The use and care of animals complied with the ARVO statement.This study protocol was approved by an Ethics Committee of Peking University People's Hospital (No.2019PHE059). Results:The three kinds of cultured cells in BSS and CEIIS groups were damaged in various degrees.With the extension of culture time, proliferated cells were decreased and the number of apoptotic cells was increased.Compared with the BSS group, cultured cells in the CEIIS group were dense and in orderly arrangement with uniform morphology and size.The apoptosis rates of HRPE cells and RGC in the BSS group were (37.157±6.918)% and (29.993±12.330)%, respectively, which were significantly higher than (4.163±1.310)% and (6.337±1.903)% in the CEIIS group ( P=0.003, 0.045). There was no significant difference in G0/G1+ S phase ratio of HCEC and HRPE cells among the normal control group, BSS group and CEIIS group (HCEC: F=2.226, P=0.189; HRPE: F=2.634, P=0.151), and the proportion of G2/M division arrest phase of RGC in the BSS group was significantly higher than that in the normal control group and CEIIS group ( P=0.047, 0.024). The proliferation absorbance values of HCEC, HRPE cells and RGC in the CEIIS group were significantly higher than those in the BSS group at each culture time point (all at P<0.05). The fluorescence intensity of cytochrome C, bax, caspase-3 and caspase-9 proteins in the BSS group was stronger than that in the normal control group and CEIIS group, and the fluorescence intensity of bcl-2 was weaker than that in the CEIIS group, and the fluorescence intensity of zonula occluden-1 (ZO-1) was weaker than that in the normal control group and CEIIS group.The release level of LDH in the BSS group was significantly higher than that in the CEIIS group at different time points (all at P<0.001). After 48 hours of culture, the release level of SDH in the BSS group was significantly higher than that in the CEIIS group ( P<0.05). No retinal histological abnormalities was found through OCT examination of rabbit eyes after vitrectomy in the two groups, but transmission electron microscopy showed that there were different degrees of loose arrangement of retinal photoreceptor cells, a large number of photoreceptor outer membrane discs falling off and vacuolar degeneration in the two groups, especially in the BSS group.TUNEL staining showed that the apoptotic cells were mainly located in the inner nuclear layer and RGC layer.The number of apoptotic retinal cells was (135.2±22.8)/high-power field of vision in the BSS group, which was significantly higher than (81.3±17.7)/high-power field of vision in the CEIIS group ( t=4.175, P=0.002). Full field flash ERG showed that the amplitudes of scotopic 3.0 ERG a- and b-wave in the CEIIS group after operation were significantly lower than those before operation, but the differences were not statistically significant (all at P>0.05). The amplitudes of scotopic 3.0 ERG a- and b-wave in the BSS group after operation were significantly lower than those before operation ( P=0.026, 0.010). Conclusions:In vivo and in vitro research results show that compared with BSS, there were few apoptotic cells in retinal tissue after vitrectomy perfused by CEIIS.

βE2 activates Nrf2 pathway to resist light-induced retinal dysfunction in rats / 西安交通大学学报(医学版)

【Objective】 To investigate whether 17β-estradiol (βE2) can activate the NF-E2-related factor 2(Nrf2) pathway to resist the downregulation of retinal function induced by light damage. 【Methods】 Two weeks after female SD rats were castrated, they were divided into the following six groups: control group (control), light-damage group (LD), saline group, saline light-damage group (saline-LD), βE2 group, and βE2 light-damage group (βE2-LD). Rats in the light-damage were exposed to 8000-lux fluorescence for 12 h after 18 h of dark adaptation. Then electroretinogram (ERG), immunofluorescence, Real-time PCR and immunohistochemical detection were performed after one day of dark recovery. 【Results】 The results of ERG showed that ERG was lower in LD group than in control group (P<0.05). After light damage, ROS was increased and the mRNA expressions of antioxidant genes, such as Sod1, Sod2, Cat, Glrx1, Glrx2, Txn1, and Txn2 were decreased (all P<0.05). After βE2 administration, compared with those in saline-LD, ROS level was decreased, the levels of Nrf2 protein and antioxidant genes were increased, and ERG was recovered to a certain extent in βE2-LD (P<0.05). 【Conclusion】 βE2 can restore the function of rat retina, and its mechanism might be related to the upregulation of Nrf2 and antioxidant genes.

Preventive and therapeutic effects of Keluoxin Capsules on early diabetic retinopathy in db/db mice / 中国中药杂志

The aim of this paper was to investigate the preventive effects of Keluoxin Capsules(KLX) on diabetic retinopathy in db/db mice. One hundred male db/db diabetic mice(45-55 g, 8 weeks) were randomly divided into 5 groups(model, KLX low dose, KLX middle dose, KLX high dose, Dobesilate) and 20 male C57 BL/KsJdb~(+/+) were taken as control group. Body weight and fasting blood-glucose were detected every week. Mice were administrated with saline(control and model group), KLX(780, 1 560, 3 120 mg·kg~(-1)·d~(-1), ig), Dobesilate(195 mg·kg~(-1)·d~(-1), ig) for 20 weeks, respectively. At the end of the administration, optical coherence tomography, fundus fluorescein angiography and electroretinogram of the retina were measured. The eyeball was extirpated and retina was isolated to make paraffin section, followed by HE staining and glial fibrillary acidic protein(GFAP) immunohistochemistry. The results indicated that KLX has no obvious effect on body weight and fasting blood level in db/db mice. However, KLX could significantly regulate the thickness of retinal ganglion layer and inner plexiform layer. KLX was able to remarkably reduce the quantity of diabetic microvessel. Meanwhile, KLX could notably improve retinal function. Moreover, KLX could observably modulate the cell arrangement and edema in each layer. There was no markable difference in retina according to the immunochemistry assay. In the present study, KLX exert marked preventive effects on diabetic retinopathy in db/db mice, which provided an experimental evidence for clinical use.

Application of retinal functional imager in retinal diseases / 眼科新进展

Newer retinal imaging technologies help us in understanding the pathogenesis of many retinal pathologies,such as diabetic retinopathy,age related macular degeneration,glaucoma and uveitis.Early detection of these retinal diseases can prevent the onset of progressive vision loss,and aid in the development of new treatment options.Retinal functional imager (RFI) is an unique and noninvasive functional imaging system.Unlike most of the available newer retinal imaging tools,the RFI not only shows retinal structural changes,but can directly monitor functional changes and measure hemodynamic parameters,such as retinal bloodflow velocity,oximetric state,etc.This article reviews the utility progress of RFI in various retinal diseases.

Research of using eIectroretinogram for diagnosising earIy diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

·Electroretinogram (ERG) is an objective examination in evaluating retinal function, which is also suitable to evaluate retinal function of multiple ophthalmic diseases. ln recent years, studies have found that ERG can find functional changes prior to morphological changes of fundus examination in early diabetics, which provides a new way for researches of pathological mechanism, early diagnosis and prognosis evaluation for diabetic retinopathy, and then also provides a new therapy for diabetic retinopathy. ln this paper, using ERG in the diagnosis of early diabetic retinopathy was reviewed.

Multifocal Electrophysiologic Findings in MEWDS: Multiple Evanescent White Dot Syndrome

PURPOSE: To evaluate the relationship between the lesions of the MEWDS, retinal dysfunction and the cause of decreased visual acuity. METHODS: A patient with a medical history, retinal finding, and the fluorescein angiographic findings consistent with the diagnosis of MEWDS is described. Full field ERG and mfERG were performed and the results was analyzed to find the relationship the visual acuity and the fluorescein angiographic findings. RESULTS: mfERG of the involved eye shows diffuse depression of the amplitude accentuated by focal areas of steep depression thought to correspond to white spot and full field ERG shows generalized depressed signal. The mfERG abnormalities seen at the presentation resolved with the resolution of visual symptoms after 1 month. CONCLUSIONS: The major symptoms of the patient is due to the decreased retinal function and the mfERG is seem to be the useful and safe tool for evaluation of the retinal function and the relationship between the symptoms and the white dots.