Quantitative Analysis Of Retina And Choroid In High Myopia By Wide-field SS-OCTA And Investigation Of Its Pathogenesis

Part Ⅰ: Quantitative Analysis of Choroid in Young Adults with Simple High Myopia by Wide-field SS-OCTAPurpose: We aimed to investigate the change of choroidal vessel volume(CVV),choroidal stroma volume(CSV)and three-dimensional choroidal vessel index(3D-CVI),vessel density of choroidal capillary plexus(CC-VD)and choroidal thickness(Ch T)in young myopic adults using swept-source optical coherence tomography angiography(SS-OCTA)and compare the difference of these indicators in different quadrants of the macula and optic disc.Methods: A total of 248 eye samples from 135 participants were used in this cross-sectional study.Each participant underwent detailed history taking and ocular examinations.Based on axial length(AL),patients were divided into the emmetropia(EM)group,mild-myopia(MIM)group,moderate-myopia(MOM)group,and high-myopia(HM)group.6 mm×6 mm(1024×1024 B-scan)SS-OCTA scans were performed centered on the fovea and optic disc.CVV、CSV、3D-CVI、CC-VD and Ch T were measured based on a built-in deep learning algorithm.Differences in Ch T,CVV,and 3D-CVI were analyzed in different regions and different myopic groups.Results:(1)Significant reduction in the global CVV were found in the HM group(1.930± 0.865)in comparison with the EM(3.486 ± 0.992),MIM(3.238 ± 1.033),and MOM(2.589 ± 1.083)groups(P < 0.001).The differences in global CVS were also statistically significant in the EM(4.812 ± 1.191),MIM(4.343 ± 1.209),MOM(3.858 ± 0.404),and HM(3.413 ± 0.607)groups(P < 0.001).The global 3D-CVI was also lower in the HM group(0.258 ± 0.061)than in the EM(0.320 ± 0.055),MIM(0.320 ± 0.051),and MOM(0.286 ± 0.066)groups(P < 0.001).The global CC-VD was also lower in the HM group(59.857 ± 2.297)compared to the EM group(74.219 ± 5.774),the MIM group(70.520 ±2.752),and the MOM group(66.222 ± 1.278)(P < 0.001).The Ch T was thinner in eyes with HM(242.753 ± 65.641)than in eyes with EM(377.532 ± 80.593),MIM(348.367 ±78.191),or MOM(300.197 ± 87.175)(P < 0.001).(2)Compartmental analysis revealed that Ch T,CVV,and 3D-CVI in the nasal quadrant of the macula and temporal and inferior quadrants of the optic disc were much lower than those in other quadrants(P < 0.05).(3)Correlation analyses found that CVV、CSV、3D-CVI、CC-VD and Ch T were negatively correlated with AL and spherical equivalence.Conclusion: CVV、CSV、3D-CVI、CC-VD and Ch T gradually decreased as the degree of myopia increased.The changes were more dramatic on the nasal side of the macula and the temporal and inferior sides of the optic disc.These findings demonstrated the 3D choroidal change and highlighted the papillo-macular bundle area as a sensitive region in myopic development.Part Ⅱ: Quantitative analysis of Retina and Choroid in DCA Patients with Pathological High Myopia by Wide-field SS-OCTAPurpose: Wide-field SS-OCTA was used to quantitatively analyze the changes in fundus circulation and thickness of pathological high myopia diffuse chorioretinal atrophy(DCA)patients,to explore the factors affecting the best corrected visual acuity(BCVA)and parapapillary atrophy(PPA)area,and to provide novel measurable parameters for clinical management and condition monitoring of pathological high myopia DCA patients.Methods: A cross-sectional study was conducted on 258 subjects(388 eyes).Each participant underwent detailed medical records and ophthalmological examinations.According to AL and myopic maculopathy(MM),patients were divided into three groups:healthy control(HC)group,simple high myopia(HM)group and pathological high myopia(PM)group.The SS-OCTA scanning center is located in the fovea of the macula and the optic papilla of the optic disc respectively,and the image is collected in the mode of 6 mm×6 mm(1024×1024 B-scan).Then the parameters of retina and choroid were measured based on the built-in depth learning algorithm and the differences of parameters in different myopia groups were analyzed.Finally,the best 3D-CVI values of predictable peripapillary diffuse chorioretinal atrophy(PDCA)and macular diffuse chorioretinal atrophy(MDCA)are determined by multiple regression analysis and receiver operating characteristic(ROC)curves.Results:(1)CVV,CSV,3D-CVI,CC-VD and Ch T of choroid decreased with the aggravation of myopia.In addition,the area and perimeter of foveal avascular zone(FAZ)decreased,the circularity index(CI)and fractal dimension(FD)of FAZ increased,the tilt ratio of optic disc decreased and the area of parapapillary atrophy(PPA)increased.(2)Through univariate and multivariate logistic regression analysis,it was found that 3D-CVI and Ch T were important factors affecting the BCVA and the area of PPA in patients with high myopia.(3)Through multiple stepwise regression analysis,it was found that the decreasing rate of 3D-CVI in the macular fovea decreased with the increase of age and the severity of myopic atrophy maculopathy(MAM),and accelerated with the increase of PPA area and the decrease of BCVA.(4)The best 3D-CVI values of PDCA and MDCA predicted by ROC curve analysis were 11.901% and 14.083% in temporal side and14.083% in inferior side of optic disc,and 12.655% in nasal side of macular region,respectively.Conclusion: Progressive and persistent choroidal thinning and the decrease of choroidal blood flow density are closely related to the development of MAM,but the causal relationship between them needs further longitudinal study and analysis.The decrease of3D-CVI and Ch T was significantly correlated with visual impairment of PM and aggravation of PPA.The threshold analysis of 3D-CVI by PDCA and MDCA suggests that clinicians should pay close attention to the changes of choroidal vessels in PM,especially in the nasal side of macula and the temporal and inferior side of optic disc,and realize that slowing or preventing the decrease of 3D-CVI may be an important clinical goal of PM treatment in the future.Part Ⅲ: Quantitative Analysis of WWOP/DWOP in High Myopic-related Peripheral Degenerations by Wide-field SS-OCTAPurpose: This study aimed to investigate the incidence of white without pressure(WWOP)and dark without pressure(DWOP)in a young myopic group based on multimode imaging and to explore the quantitative changes in DWOP based on ultra-wide swept-source optical coherence tomography angiography(SS-OCTA).Methods: A total of 138 patients(227 eyes)with high myopia(SE<-6.00 D or AL≥26.0mm)were recruited.Examinations,including indirect ophthalmoscope,ultra-wide scanning laser ophthalmoscopy,and ultra-wide SS-OCTA,were detailedly conducted for each eye.The images were acquired in five different orientations using a 12 mm×12 mm scanning mode in the ultra-wide SS-OCTA instrument.A total of 50 of the 138 patients were selected for further analysis since their DWOP lesions in SS-OCTA could be well quantified.Results:(1)The incidence rates of WWOP and DWOP in the young myopic group were35.242% and 29.956%,respectively.(2)The patients with a lower spherical equivalent(SE)showed a tendency to have a higher axial length(AL)and higher prevalence of WWOP.(3)Multivariate regression analysis illustrated that a more serious SE and a longer AL were risk factors for both WWOP and DWOP.(4)Eyes with DWOP lesions had lower vessel density(VD)in the whole retina(P < 0.001)and a deep vascular complex(DVC)(P < 0.001),and lower thickness of the outer retina(P < 0.001)compared with healthy counterparts.Conclusion: Ultra-wide SS-OCTA provided new insights into myopic-related peripheral retinal degenerations.DWOP was characterized by thinning of the outerretina and lower perfusion in DVC.Part Ⅳ: Proteomics Analysis of Aqueous Humor in Pathological High Myopic Atrophy MaculopathyPurpose: Qualitative and quantitative detection of the proteins in the aqueous humor of the myopic atrophy maculopathy(MAM)group and the non-myopic maculopathy(non-MM)group,who are high myopic cataract patients,and to investigate the pathogenesis of MAM by comparison of these differentially expressed proteins.Methods: Aqueous humor samples were collected from highly myopic cataract patients that underwent phaco-emulsification cataract surgery at our hospital from June 2021 to September 2022,including 12 eyes in 12 cases of MAM group and 12 eyes in 12 cases of non-MM group as well.Six aqueous humor samples of each group were selected for four-dimensional label-free quantitative(4D LFQ)proteomics analysis to identify differentially expressed proteins.Enzyme-linked immunosorbent assay(ELISA)was used to validate five randomly selected differentially expressed proteins,using the remaining 12 aqueous humor samples.Then,functions of the differentially expressed proteins were analyzed by bioinformatic methods.Results: In this study,71 differentially expressed proteins were identified in aqueous humor samples of patients with high myopia complicated with cataract in MAM and non-MM groups,of which 32 proteins were up-regulated and 39 proteins were down-regulated.In addition,the expression trends of five randomly selected differential proteins used for ELISA verification between MAM and non-MM groups were consistent with the results of 4D LFQ proteomics.Bioinformatics analysis shows that the occurrence and development of MAM is closely related to abnormal energy metabolism,oxidative stress,immune-inflammatory interaction and extracellular matrix remodeling.Conclusion: Compared with non-MM group,the protein expression profile in aqueous humor of patients with MAM was significantly different.These differentially expressed proteins suggest that there may be abnormal energy metabolism and oxidative stress in eyes with MAM,and immune-inflammatory interaction and extracellular matrix remodeling may provide potential clues for further research on the treatment of MAM in the future.