Objective:To quantitatively evaluate the retinal ischemia in different retinal regions of diabetic retinopathy (DR) patients in ultra-widefield fluorescein fundus angiography (UWFA) images with ischemic index (ISI), and to explore its correlation with diabetic macular edema (DME).Methods:A cross-sectional study was conducted.Seventy-nine eyes of 79 patients with DR were enrolled in Renmin Hospital of Wuhan University from September 2017 to October 2020, including 44 males (44 eyes) and 35 females (35 eyes) aged 31 to 73 years old, with an average age of (55.95±8.80) years.UWFA and spectral-domain optical coherence tomography (SD-OCT) were performed in all patients.Patients were divided into DME group (37 eyes) and non-DME group (42 eyes) according to the presence or absence of DME in OCT images.The retina in middle phase UWFA images were divided into posterior, middle peripheral and far peripheral regions by ImageJ software, and ISI in each region was calculated.Central macular thickness (CMT) was automatically calculated using the built-in software of the OCT equipment.The correlation between ISI and CMT was analyzed by Spearman rank correlation analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Renmin Hospital of Wuhan University (No.WDRY2019-K037). Written informed consent was obtained from each patient prior to any medical examination.Results:The ISI of the total, posterior, middle peripheral and far peripheral retina was 2.460 (0.603, 5.640)%, 2.670 (1.062, 9.574)%, 1.382 (0.245, 4.378)% and 0.000 (0.000, 1.262)%, respectively, with a statistically significant difference among different regions ( χ2=65.307, P<0.001). There were statistically significant differences in ISI between the total and far peripheral, the posterior and middle peripheral, the posterior and far peripheral, the middle and far peripheral (all at P<0.01). ISI of the total, posterior and middle peripheral retina in DME group were significantly higher than those in non-DME group ( U=424.000, P=0.001; U=403.000, P<0.001, U=493.000, P=0.005), but there was no significant difference in the ISI of the far peripheral region between the two groups ( U=609.000, P=0.061). There was no statistically significant correlation between ISI and CMT in the total, posterior, middle peripheral and far peripheral retina in DME group ( rs=-0.134, -0.018, -0.152, -0.163; all at P>0.05). Conclusions:The retinal non-perfusion area in DR eyes is mainly located in the posterior and middle peripheral retina.The ISI of the posterior and middle peripheral retina in DME eyes is significantly higher than that in eyes without DME.ISI of each retinal region may not be related to the severity of DME.

Non-arteritic anterior ischemic optic neuropathy (NAION) is an optic neuropathy that usually occurs in people over 50 years old.The pathogenesis of NAION remains unknown, and there is no recognized effective treatment.The animal model of NAION established by photodynamic method has similar fundus and electrophysiological changes to clinical NAION.In recent years, studies on the pathological mechanisms of NAION based on animal models have found that axonal structure destruction, demyelination and inflammatory cells infiltration in the region of optic nerve infarction, accompanied by secondary retinal ganglion cells apoptosis.There are a wide range of drugs for NAION based on animal models, including glucocorticoids, granulocyte colony-stimulating factor, prostaglandin J2, anti-vascular endothelial growth factor, neurotrophic factors, effective drugs for glaucoma or central nervous system damage, etc.Routes of administration include systemic administration, intravitreal injection or topical application of eye drops.The neuroprotective effects of some drugs in animal models provide a basis for clinical screening of new therapeutic drugs.In this review, the animal models of NAION, pathophysiology and treatment based on animal models were summarized.

Objective:To observe the choroidal vascular changes of chronic central serous chorioretinopathy (cCSC), and analyze their correlations with central macular thickness (CMT).Methods:A cross-sectional study was adopted.Seventy-six eyes of 38 patients with monocular cCSC who were treated in Renmin Hospital of Wuhan University from March 2018 to December 2019 were enrolled, and 30 eyes of 30 normal control matched with age, gender, and spherical equivalent (SE) were included.Choroidal images of all subjects, and the CMT, subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI), total choroidal area (TCA), choroidal stromal area (SA), and choroidal luminal area (LA) were measured by Heidelberg enhanced depth imaging optical coherence tomography.The differences in SFCT, LA, SA, TCA, CMT and CVI between the cCSC eye, fellow eye and normal eye, as well as the correlation between SFCT and CVI, SFCT and CMT, and CVI and CMT were analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Renmin Hospital of Wuhan University (No.WDRY2020-K234).Results:The CVI and the SFCT of the cCSC eyes, fellow eyes and normal eyes were (71.67±5.60)% and 483.82(409.01, 550.87)μm, (68.33±3.85)% and 444.66(351.25, 505.15)μm, (64.70±1.88)% and 373.46(327.98, 405.48)μm, respectively.The CMT, SFCT, TCA, LA, CVI in cCSC eyes were significantly higher than those in the contralateral eyes and normal control eyes, while SFCT, TCA, LA, CVI in the contralateral eyes were higher than those in normal control eyes (all at P<0.05). Pairwise comparison among the three groups showed no significant difference in SA (all at P>0.05). Correlation analysis showed that in cCSC eyes, SFCT was strongly positively correlated with CVI ( rs=0.703, P<0.001), and there was no correlation between CMT and SFCT ( rs=0.181, P=0.278), or CMT and CVI ( r=0.231, P=0.164). Conclusions:The SFCT and CVI are higher in cCSC and the fellow eyes compared with normal eyes, and the choroidal vessels are significantly dilated in cCSC patients.The SFCT and CVI of the cCSC eye are slightly higher in comparison with the fellow eye.CMT is not correlated with SFCT or CVI in cCSC eyes.

Objective:To build a small-sample ultra-widefield fundus images (UWFI) multi-disease classification artificial intelligence model, and initially explore the ability of artificial intelligence to classify UWFI multi-disease tasks.Methods:A retrospective study. From 2016 to 2021, 1 608 images from 1 123 patients who attended the Eye Center of the Renmin Hospital of Wuhan University and underwent UWFI examination were used for UWFI multi-disease classification artificial intelligence model construction. Among them, 320, 330, 319, 268, and 371 images were used for diabetic retinopathy (DR), retinal vein occlusion (RVO), pathological myopia (PM), retinal detachment (RD), and normal fundus images, respectively. 135 images from 106 patients at the Tianjin Medical University Eye Hospital were used as the external test set. EfficientNet-B7 was selected as the backbone network for classification analysis of the included UWFI images. The performance of the UWFI multi-task classification model was assessed using the receiver operating characteristic curve, area under the curve (AUC), sensitivity, specificity, and accuracy. All data were expressed using numerical values and 95% confidence intervals ( CI). The datasets were trained on the network models ResNet50 and ResNet101 and tested on an external test set to compare and observe the performance of EfficientNet with the 2 models mentioned above. Results:The overall classification accuracy of the UWFI multi-disease classification artificial intelligence model on the internal and external test sets was 92.57% (95% CI 91.13%-92.92%) and 88.89% (95% CI 88.11%-90.02%), respectively. These were 96.62% and 92.59% for normal fundus, 95.95% and 95.56% for DR, 96.62% and 98.52% for RVO, 98.65% and 97.04% for PM, and 97.30% and 94.07% for RD, respectively. The mean AUC on the internal and external test sets was 0.993 and 0.983, respectively, with 0.994 and 0.939 for normal fundus, 0.999 and 0.995 for DR, 0.985 and 1.000 for RVO, 0.991 and 0.993 for PM and 0.995 and 0.990 for RD, respectively. EfficientNet performed better than the ResNet50 and ResNet101 models on both the internal and external test sets. Conclusion:The preliminary UWFI multi-disease classification artificial intelligence model using small samples constructed in this study is able to achieve a high accuracy rate, and the model may have some value in assisting clinical screening and diagnosis.

Objective:To observe and preliminarily discuss the distribution characteristics of the non-perfusion area (NP) of the retina in different stages of diabetic retinopathy (DR) and its changes with the progression of DR.Methods:A retrospective clinical study. From October 2018 to December 2020, 118 cases of 175 eyes of DR patients diagnosed in Eye Center of Renmin Hospital of Wuhan University were included in the study. Among them, there were 64 males with 93 eyes and 54 females with 82 eyes; the average age was 56.61±8.99 years old. There were 95 eyes of non-proliferative DR (NPDR), of which 25, 47, and 23 eyes were mild, moderate, and severe; 80 eyes were proliferative DR (PDR). Ultra-wide-angle fluorescein fundus angiography was performed with the British Optos 200Tx imaging system, and the fundus image was divided into posterior, middle, and distal parts with Image J software, and the ischemic index (ISI) was calculated. The difference of the retina in different DR staging groups and the difference of ISI were compared in the same area. The Kruskal-Wallis test was used to compare the ISI between the different DR staging groups and the Kruskal-Wallis one-way analysis of variance was used for the pairwise comparison between the groups.Results:The ISI of the posterior pole of the eyes in the moderate NPDR group, severe NPDR group, and PDR group were significantly greater than that in the distal periphery, and the difference was statistically significant ( χ 2=6.551, 3.540, 6.614; P=0.000, 0.002, 0.000). In severe NPDR group and PDR group, the ISI of the middle and peripheral parts of the eyes was significantly greater than that of the distal parts, and the difference was statistically significant ( χ 2=3.027, 3.429; P=0.015, 0.004). In the moderate NPDR group, there was no significant difference in ISI between the peripheral and distal parts of the eye ( χ 2=2.597, P=0.057). The ISI of the posterior pole of the eyes in the moderate NPDR group and the PDR group was significantly greater than that in the middle periphery, and the difference was statistically significant ( χ 2=3.955, 3.184; P=0.000, 0.009). In the severe NPDR group, there was no significant difference in ISI between the posterior pole and the middle periphery of the eye ( χ 2=0.514, P=1.000). Compared with the mild NPDR group and the moderate NPDR group, the ISI of the whole retina, posterior pole, middle and distal parts of the PDR group was larger, and the difference was statistically significant ( χ 2=-7.064, -6.349,-6.999, -5.869, -6.695, -6.723, -3.459, -4.098; P=0.000, 0.000, 0.000, 0.000, 0.000, 0.000, 0.003, 0.000). Conclusion:The NP of the eyes with different DR stages is mainly distributed in the posterior pole and the middle periphery. The higher the severity of DR, the greater the NP in the posterior and middle periphery.

Objective:To analyze the peripheral retinal fluorescence characteristics of normal fundus on ultra-wide field fluorescein angiography (UWFA) images.Methods:A cross-sectional study was conducted.Ninety-five patients (190 eyes) who underwent normal UWFA in Renmin Hospital of Wuhan University from July 2016 to January 2019 were enrolled.There were 94 (49.47%) male eyes and 96 (50.53%) female eyes.Among them, there were 72 (37.89%) mild cataract eyes, 60 (31.58%) moderate and low myopia eyes and 58 (30.53%) subjective blurred vision eyes.The peripheral retinal fluorescence characteristics were divided into vascular-associated feature or non-vascular feature according to whether the retinal vessel involved or not.The subjects were divided into ≤40 years old group and >40 years old group, and the differences in various features between the two groups were compared and analyzed.The study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of Renmin Hospital of Wuhan University (No.WDRY2019-K037). Written informed consent was obtained from each patient prior to any examination.Results:Four non-vascular and five vascular-associated fluorescence features were found in normal peripheral retina.Non-vascular features contained glass hyperfluorescence in 158 (83.16%) eyes, far peripheral retina with mottled florescent band in 82 (43.16%) eyes, granular ground hyperfluorescence in 24 (12.63%) eyes and local mottled fluorescence in 21 (11.05%) eyes.Vascular-associated fluorescence features included peripheral avascular area in 92 (48.42%) eyes, vessels passing through the ora serrata in 66 (34.74%) eyes, microaneurysm in 60 (31.58%) eyes, slight leakage within 10 minutes after angiography in 56 (29.47%) eyes and angiotelectasis in 30 (15.79%) eyes.There were 19.61% (20/102) of eyes with peripheral retinal vessels passing through the ora serrata and 43.10% (44/102) of eyes with microaneurysm and 19.61% (20/102) of eyes with angiotelectasis in >40 years old group, and there were 52.27% (46/88), 18.23% (16/88) and 11.36% (10/88) correspondingly in ≤40 years old group, and the differences were statistically significant ( χ2=22.235, 10.451, 9.259; all at P<0.01). Conclusions:UWFA reveals four non-vascular and five vascular-associated fluorescence characteristics of normal fundus and age might be associated with the distribution of microaneurysm and angiotelectasis.

Objective:To investigate the features of multicolor imaging in the macular region of central serous chorioretinopathy (CSC) patients.Methods:A cross-sectional study was conducted.Thirty-four acute CSC patients (34 eyes) treated in Renmin Hospital of Wuhan University from August 2017 to January 2018 were enrolled.Among the 34 subjects, there were 21 males (21 eyes) and 13 females (13 eyes). The subjects were 26 to 61 years old, with an average age of (37.41±9.35) years.The course of the disease was 5 to 45 days, with an average course of (12.00±2.29) days.All the subjects were examined by color fundus photography, fluorescein angiography (FFA), indocyanine green angiography (ICGA), multicolor imaging, spectral-domain optical coherence tomography (SD-OCT). The image features of each patient were compared and analyzed.The diagnostic accordance rate for leakage point and serous retinal neuroepithelial detachment of multicolor imaging and color fundus photography was calculated according to FFA/ICGA and OCT.This study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of Renmin Hospital of Wuhan University (No.WDRY2019-K037).Results:The serous retinal detachment region showed green light reflection area with clear boundary in 33 eyes (97.06%) in the standard as well as blue and green enhanced multicolor image, with not clear boundary in 1 eye (2.94%). The serous retinal detachment region showed weakly reflective area in 17 eyes (50%) in blue reflectance image, showed weak reflection with clear boundary in 32 eyes (94.11%) in green reflectance image, showed weakly reflection with clear boundary in 33 eyes (97.06%) in infrared reflectance image.The fluorescein leakage point in FFA image was found micro retinal pigment epithelium detachment (PED) in 19 eyes (55.88%), rough light band of retinal pigment epithelium (RPE) in 12 eyes (35.29%), and large PED in 3 eyes (8.82%) in SD-OCT image.The RPE leakage showed red mottled changes in the area of neuroepithelial detachment in 29 eyes (85.29%) in the standard as well as blue and green enhanced multicolor images, presented strong reflection spots in blue reflectance images in 2 eyes (5.88%), showed strong reflective spots in green reflectance in 5 eyes (14.70%), showed strong reflection spot in the weakly reflective area in 33 eyes (97.06%) in infrared reflectance images.Taking FFA/ICGA and OCT as the gold standard, the diagnostic accordance rate of standard multicolor, blue and green enhanced multicolor and infrared reflectance images for serous retinal neuroepithelial detachment and leakage points was higher than that of color fundus photography, and the differences were statistically significant (all at P<0.05). Conclusions:Standard multicolor, blue and green enhanced multicolor and infrared reflectance images can reflect the leakage point and retinal neuroepithelial detachment of acute CSC.Green reflectance image can show serous retinal neuroepithelial detachment of acute CSC.Multicolor imaging can be used as the auxiliary diagnosis method of acute CSC.

Objective:To explore the application of multispectral fundus imaging (MSI) in central serous chorioretinopathy (CSC).Methods:A diagnostic test study was conducted.Eighty-five eyes from 69 patients with macular diseases were enrolled in Renmin Hospital of Wuhan University from September 2017 to May 2018.There were 62 males (77 eyes) and 7 females (8 eyes) among the 69 patients with an average age of (48.0±11.2) years.The patients were divided into CSC group (45 cases, 61 eyes) and non-CSC group (24 cases, 24 eyes) according to whether suffering from CSC or not.Color fundus photography, fundus fluorescein angiography (FFA), indocyanine green angiography, spectral domain-optical coherence tomography and MSI were performed in the two groups and the images were collected.With FFA as the gold standard, the sensitivity, specificity, false positive rate, false negative rate, positive predictive value and negative predictive value of MSI in the diagnosis of CSC were calculated.Kappa consistency test was used to evaluate the consistency of MSI and FFA in diagnosing CSC, and to evaluate the diagnostic value of MSI in CSC.This study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of Renmin Hospital of Wuhan University (No.WDRY2019-K037). Written informed consent was obtained from each subject prior to any medical examination.Results:The sensitivity, specicity, false positive rate, false negative rate, positive predictive value and negative predictive value of MSI for identifying CSC were 88.5%, 91.7%, 8.3%, 11.5%, 96.4% and 75.9%, respectively.The Kappa coefficient of agreement was 0.754.There was no significant difference in the identification of CSC between MSI and FFA ( χ2=1.780, P=0.180). Hyper-reflective signals corresponding to the leakage points were better detected with MSI images at 620-850 nm wavelength.The clear boundary of serous neuroepithelial detachment area was better detected with MSI images at 590-810 nm wavelength.The retinal pigment epithelium damage was better detected with MSI images at 660-850 nm wavelength. Conclusions:There is a good consistency between MSI and FFA.MSI can be an effective noninvasive inspection method for CSC.

Objective To observe the imaging features of cystoid macular edema (CME) in multicolor imaging (MC),and to evaluate the value of MC in the diagnosis of CME.Methods Descriptive case series study.From August 2017 to June 2018,42 eyes of 37 patients with CME diagnosed in the people's Hospital of Wuhan University were included in the study.Among them,there were 24 males and 13 females,with an average age of 48.51 ± 10.29 years.There were 14 eyes with diabetic retinopathy,14 eyes with central retinal vein occlusion,8 eyes with branch retinal vein occlusion,4 eyes with uveitis,and 2 eyes with Eales disease.The macular color fundus photography (CFP) was performed with Visucam 200 non-mydriatic fundus camera of Zeiss company in Germany.MC,frequnce domainoptical OCT (SD-OCT) and FFA were examined by Spectralis HRA2 + OCT of Heidelberg company in Germany.According to the MC standard method,five images,including 488 nm blue reflection (BR),515 nm green reflection (GR),820 nm infrared reflection (IR) imaging and standard MC and blue-green enhancement (BG),were obtained at the same time.Compared with SD-OCT,CFP and MC images were scored.Friedman M test and Wilcoxon signed rank test were used for statistical analysis.Results The standard MC and BG images showed blue-green uplift area or petal-shaped appearance,surrounded by green reflection areas with clear boundaries.BR image can be seen in the low reflexes area.On the GR image,there were patches or cystic low reflection areas,surrounded by a slightly high reflection.On the IR image,patches or cystoid high reflexes can be seen,surrounded by low reflection dark areas with clear boundaries.The average scores of CFP,standard MC,GB,IR,GR and BR were 1.20± 0.94,3.05± 0.99,2.90± 1.04,2.55± 1.27,2.00± 0.94,0.51 ± 0.85 respectively,and the differences were statistically significant (χ2=151.61,P=0.000).The score of CFP were significantly lower than that of standard MC (Z=-5.421),BG (Z=-5.354),IR (Z=-4.714),GR (Z=-4.438) and higher than that of BR (Z=-3.435).The differences were statistically significant (P=0.000,0.000,0.000,0.000,0.001).Conclusions The quality of MC imaging is better than that of CFP.Combined with SD-OCT,it can be used as an assistant method to diagnose CME.

Objective To assess changes of blood flow density of idiopathic choroidal neovascularization (ICNV) treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF).Methods Retrospective case analysis.Sixteen eyes of 16 patients with ICNV diagnosed with FFA and OCT were included in this study.Among them,12 were female and 4 were male.The mean age was 33.94±9.83 years.The mean course of diseases was 5.13 ±4.44 weeks.The BCVA,indirect ophthalmoscope,OCT and OCT angiography (OCTA) were performed at the first diagnosis in all patients.The BCVA was converted to logMAR.The macular fovea retinal thickness (CMT) was measured by OCT,and the selected area of CNV (CSA) and flow area of CNV (CFA) were measured by OCTA.The mean logMAR BCVA,CMT,CSA and CFA were 0.336±0.163,268.500±57.927 μm,0.651 ±0.521 mm2,0.327±0.278 mm2,respectively.All patients were treated with intravitreal ranibizumab (IVR,10 mg/ml,0.05 ml).Follow-up results including the BCVA,fundus color photography,OCT and OCTA were obtained 1 month after treatment.To compare the changes ofBCVA,CMT,CSA,CFA of ICNV treated with anti-VEGF.Pearson method was used to analyze the correlation between logMAR BCVA and CMT,CSA and CFA before and after the treatment.Results One month after treatment,the average logMAR BCVA,CMT,CSA and CFA were 0.176±0.111,232.500± 18.910 μm,0.420±0.439 mm2,0.215 ± 0.274 mm2.The mean logMAR BCVA (t=5.471,P＜ 0.001),CMT (t=2.527,P=0.023),CSA (t=4.039,P=0.001),CFA (t=4.214,P=0.001) significantly decreased at 1 month after injection compared to baseline,and the difference had statistical significance.The results of correlation analysis showed that the post-logMAR BCVA was moderately positively correlated with pre-CSA and post-CSA (r=0.553,0.560;P=0.026,0.024),and strongly correlated with pre-CFA and post-CFA (r=0.669,0.606;P=0.005,0.013),but not correlated with preCMT and post-CMT (r=0.553,0.560;P=0.026,0.024).Conclusion The blood flow density of ICNV measured by OCTA were significantly decreased in the treatment of anti-VEGF drugs.