Background:The goal of this review is to summarize structural and anatomical changes associated with high myopia.Main text:Axial elongation in myopic eyes is associated with retinal thinning and a reduced density of r...Background:The goal of this review is to summarize structural and anatomical changes associated with high myopia.Main text:Axial elongation in myopic eyes is associated with retinal thinning and a reduced density of retinal pigment epithelium(RPE)cells in the equatorial region.Thickness of the retina and choriocapillaris and RPE cell density in the macula are independent of axial length.Choroidal and scleral thickness decrease with longer axial length in the posterior hemisphere of the eye,most marked at the posterior pole.In any eye region,thickness of Bruch’s membrane(BM)is independent of axial length.BM opening,as the inner layer of the optic nerve head layers,is shifted in temporal direction in moderately elongated eyes(axial length<26.5 mm).It leads to an overhanging of BM into the intrapapillary compartment at the nasal optic disc side,and to an absence of BM at the temporal disc border.The lack of BM at the temporal disc side is the histological equivalent of parapapillary gamma zone.Gamma zone is defined as the parapapillary region without BM.In highly myopic eyes(axial length>26.5 mm),BM opening enlarges with longer axial length.It leads to a circular gamma zone.In a parallel manner,the peripapillary scleral flange and the lamina cribrosa get longer and thinner with longer axial length in highly myopic eyes.The elongated peripapillary scleral flange forms the equivalent of parapapillary delta zone,and the elongated lamina cribrosa is the equivalent of the myopic secondary macrodisc.The prevalence of BM defects in the macular region increases with longer axial length in highly myopic eyes.Scleral staphylomas are characterized by marked scleral thinning and spatially correlated BM defects,while thickness and density of the choriocapillaris,RPE and BM do not differ markedly between staphylomatous versus non-staphylomatous eyes in the respective regions.Conclusions:High axial myopia is associated with a thinning of the sclera and choroid posteriorly and thinning of the retina and RPE density in the equator展开更多
Purpose: The primary aim of this paper is to design, create, and improve functional and artificial Bruch’s membranes (BM) using bioengineering techniques, which can be applied in the treatment of maculopathies by sup...Purpose: The primary aim of this paper is to design, create, and improve functional and artificial Bruch’s membranes (BM) using bioengineering techniques, which can be applied in the treatment of maculopathies by supporting the growth and maintenance of retinal pigment epithelium (RPE) cells, thereby potentially enabling subretinal implantation in patients. Methods: We fabricated by electrospinning ultrathin 3D nanofibrous membranes from Polycaprolactone (PCL), and different concentrations of gelatin (5%, 15% and 30%). ARPE-19 cells were seeded onto these artificial membranes. MTT assays were performed in order to evaluate ARPE-19 cell viability and cytotoxicity. IF assays were realized to observe the ARPE-19 cells onto each membrane. Ultrastructure of the modified Bruch’s membrane and ARPE-19 morphology after 25 days of culture were studied with transmission and scanning electron microscopy. To evaluate expression changes in markers of ARPE-19 (RPE65 and ZO-1) qRT-PCR assays were realized. Data from three independent experiments were pooled and expressed as the mean SD. A confidence level of P 0.05 was considered to be statistically significant. Results ARPE-19 cells grew on PCL/Gelatin membranes mainly in PCL/30% gelatin combination, which had not cytotoxic effect. RPE65/cytokeratin-18/ and actin-positive ARPE-19 cells formed a correctly orientated monolayer of polygonal cells with morphological polarity. The apical cell surfaces exhibited abundant protruding microfolds. Moreover, zones of polygonal border look as if ARPE-19 cells fused among, suggesting the presence of tight junctions. The expression of RPE65 and ZO-1 was unchanged. Conclusions: PCL/30% Gelatine membranes may imitate the natural BM to such extent that they support RPE-cells and exhibited RPE-like morphology. The engineering of a human RPE monolayer with these artificial BM, emulating the in vivo retina, arouse their potential subretinal implantation in patients with wet age-related macular degeneration (AMD) where there is a rupture of the展开更多
AIM: To compare the ocular fundus features of highly myopic eyes with and without macular Bruch’s membrane(BM) defects and investigate the associations between macular BM defects and other myopic lesions.METHODS: Thi...AIM: To compare the ocular fundus features of highly myopic eyes with and without macular Bruch’s membrane(BM) defects and investigate the associations between macular BM defects and other myopic lesions.METHODS: This retrospective, observational case series included 262 eyes(139 patients) with high myopia(HM) refractive error ≥-6.0 diopters(D) or axial length ≥26.5 mm from March 2019 to December 2019.The patients underwent a comprehensive ophthalmic examination, including sweptsource optical coherence tomography(SS-OCT).The features of macular BM defects and other ocular fundus lesions were examined in OCT images.RESULTS: Totally 51 eyes(19.5%) were detected with macular BM defects, which were characterized by a lack of BM, retinal pigment epithelium(RPE), and an almost complete loss of photoreceptors or choriocapillaris.Eyes with macular BM defects had worse best-corrected visual acuity(BCVA) than those without(P<0.001).Dome-shaped macula(DSM, P=0.042), retinal cysts(P=0.006), choroidal neovascularization(CNV, P<0.001), choroidal defects and abnormality(P=0.003), scleral defects(P=0.015), scleral deformation(P=0.005), posterior staphyloma(P=0.011), and perforating vessels(P<0.001) occurred more frequently in eyes with macular BM defects.In multivariate analysis, the presence of macular BM defects remained the significant association with presence of DSM(P=0.013), scleral defects(P=0.015), posterior staphyloma(P=0.001), perforating vessels(P<0.001) and CNV(P=0.004).CONCLUSION: Macular BM defects has a prevalence of approximately 20% in HM and it has tight association with other myopic fundus lesions.BM might be crucial in the pathogenesis of myopic fundus lesions due to its biomechanical function.A comprehensive understanding of BM’s role is useful for further researches about myopic lesions.展开更多
Age-related macular degeneration,a multifactorial inflammatory degenerative retinal disease,ranks as the leading cause of blindness in the elderly.Strikingly,there is a scarcity of curative therapies,especially for th...Age-related macular degeneration,a multifactorial inflammatory degenerative retinal disease,ranks as the leading cause of blindness in the elderly.Strikingly,there is a scarcity of curative therapies,especially for the atrophic advanced form of age-related macular degeneration,likely due to the lack of models able to fully recapitulate the native structure of the outer blood retinal barrier,the prime to rget tissue of age-related macular degeneration.Standard in vitro systems rely on 2D monocultures unable to adequately reproduce the structure and function of the outer blood retinal barrier,integrated by the dynamic interaction of the retinal pigment epithelium,the Bruch's membrane,and the underlying choriocapillaris.The Bruch's membrane provides structu ral and mechanical support and regulates the molecular trafficking in the outer blood retinal barrier,and therefo re adequate Bruch's membrane-mimics are key for the development of physiologically relevant models of the outer blood retinal barrie r.In the last years,advances in the field of biomaterial engineering have provided novel approaches to mimic the Bruch's membrane from a variety of materials.This review provides a discussion of the integrated properties and function of outer blood retinal barrier components in healt hy and age-related macular degeneration status to understand the requirements to adequately fabricate Bruch's membrane biomimetic systems.Then,we discuss novel materials and techniques to fabricate Bruch's membrane-like scaffolds for age-related macular degeneration in vitro modeling,discussing their advantages and challenges with a special focus on the potential of Bruch's membrane-like mimics based on decellularized tissue.展开更多
AIM：To evaluate and compare structural optical coherence tomography（OCT）-based parameters,such as Bruch’s membrane opening-minimum rim width（BMO-MRW）,and retinal nerve fiber layer（RNFL）thickness in glaucoma pa...AIM：To evaluate and compare structural optical coherence tomography（OCT）-based parameters,such as Bruch’s membrane opening-minimum rim width（BMO-MRW）,and retinal nerve fiber layer（RNFL）thickness in glaucoma patients with visual field（VF）defects,and to correlate both to mean deviation（MD）values of obtained standard achromatic perimetry（SAP）examinations.METHODS：Patients with glaucoma and glaucomatous VF defects were enrolled in this prospective study and compared to age-matched healthy individuals.All study participants underwent a full ophthalmic examination and VF testing with SAP.Peripapillary RNFL thickness and BMO-MRW were acquired with SD-OCT.Correlation analyses between obtained global functional and global as well as sectorial structural parameters were calculated.RESULTS：A consecutive series of 30 glaucomatous right eyes of 30 patients were included and compared to 36healthy right eyes of 36 individuals in the control group.Global MD of values correlated significantly with global RNFL（Pearson corr.coeff：0.632,P=0.001）and global BMO-MRW（Pearson corr.coeff：0.746,P〈0.001）values in the glaucoma group.Global MD and sectorial RNFL or BMO-MRW values correlated less significantly.In the control group,MD values did not correlate with RNFL or BMO-MRW measurements.A subgroup analysis of myopic patients（〉4 diopters）within the glaucoma group（n=6）revealed a tendency for higher correlations between MD and BMO-MRW than MD and RNFL measurements.CONCLUSION：In a clinical setting,RNFL thickness and BMO-MRW correlate similarly with global VF sensitivity in glaucoma patients with BMO-MRW showing higher correlations in myopic glaucoma patients.展开更多
AIM:To assess the agreement of optical coherence tomography(OCT)algorithm-based retinal pigment epithelium–Bruch’s membrane complex volume(RBV)with fundus photograph-based age-related macular degeneration(AMD)gradin...AIM:To assess the agreement of optical coherence tomography(OCT)algorithm-based retinal pigment epithelium–Bruch’s membrane complex volume(RBV)with fundus photograph-based age-related macular degeneration(AMD)grading.METHODS:Digital color fundus photographs(CFPs)and spectral domain OCT images were acquired from 96 elderly subjects.CFPs were graded according to Age-Related Eye Disease Study(AREDS)classification.OCT image segmentation and RBV data calculation were done with OrionTM software.Univariate and multivariate analyses were performed to find out whether AMD lesion features associated with higher RBVs.RESULTS:RBV correlated with AMD grading(rs=0.338,P=0.001),the correlation was slightly stronger in early AMD(n=52;rs=0.432,P=0.001).RBV was higher in subjects with early AMD compared with those with no AMD lesions evident in fundus photographs(1.05±0.20 vs 0.96±0.13 mm3,P=0.023).In multivariate analysis higher RBVs were associated significantly with higher total drusen(β=0.388,P=0.027)and pigmentation areas(β=0.319,P=0.020)in fundus photographs,whereas depigmentation area(β=-0.295,P=0.015)associated with lower RBV.CONCLUSION:RBV correlate with AMD grading status,with a stronger association in patients with moderate,non-late AMD grades.This effect is driven mostly by lesions with drusen or pigmentation.Lesions with depigmentation tend to have lower values.RBV is more comprehensive measurement of the key area of AMD pathogenesis,compared to sole drusen volume analysis.RBV measurements are independent on grader variations and offer a possibility to quantify early and middle grade AMD lesions in a research setting,but may not substitute fundus photograph-based grading in the whole range of AMD spectrum.展开更多
Background:The goal of this review is to summarize structural and anatomical changes associated with high myopia.Main text:Axial elongation in myopic eyes is associated with retinal thinning and a reduced density of r...Background:The goal of this review is to summarize structural and anatomical changes associated with high myopia.Main text:Axial elongation in myopic eyes is associated with retinal thinning and a reduced density of retinal pigment epithelium(RPE)cells in the equatorial region.Thickness of the retina and choriocapillaris and RPE cell density in the macula are independent of axial length.Choroidal and scleral thickness decrease with longer axial length in the posterior hemisphere of the eye,most marked at the posterior pole.In any eye region,thickness of Bruch's membrane(BM)is independent of axial length.BM opening,as the inner layer of the optic nerve head layers,is shifted in temporal direction in moderately elongated eyes(axial length<26.5 mm).It leads to an overhanging of BM into the intrapapillary compartment at the nasal optic disc side,and to an absence of BM at the temporal disc border.The lack of BM at the temporal disc side is the histological equivalent of parapapillary gamma zone.Gamma zone is defined as the parapapillary region without BM.In highly myopic eyes(axial length>26.5 mm),BM opening enlarges with longer axial length.It leads to a circular gamma zone.In a parallel manner,the peripapillary scleral flange and the lamina cribrosa get longer and thinner with longer axial length in highly myopic eyes.The elongated peripapillary scleral flange forms the equivalent of parapapillary delta zone,and the elongated lamina cribrosa is the equivalent of the myopic secondary macrodisc.The prevalence of BM defects in the macular region increases with longer axial length in highly myopic eyes.Scleral staphylomas are characterized by marked scleral thinning and spatially correlated BM defects,while thickness and density of the choriocapillaris,RPE and BM do not differ markedly between staphylomatous versus non-staphylomatous eyes in the respective regions.Conclusions:High axial myopia is associated with a thinning of the sclera and choroid posteriorly and thinning of the retina and reduction of RPE density in 展开更多
AIM：To determine the Bruch＇s membrane opening-minimum rim width（BMO-MRW） tipping point where corresponding visual field（VF） damages become detectable.METHODS：A total of 85 normal subjects and 83 glaucoma patie...AIM：To determine the Bruch＇s membrane opening-minimum rim width（BMO-MRW） tipping point where corresponding visual field（VF） damages become detectable.METHODS：A total of 85 normal subjects and 83 glaucoma patients（one eye per participant） were recruited for the study.All of the patients had VF examinations and spectral-domain optical coherence tomography to measure the BMO-MRW.Total deviation values for 52 VF points were allocated to the corresponding sector according to the Garway-Heath distribution map.To evaluate the relationship between VF loss and BMOMRW measurements,a ＂broken-stick＂ statistical model was used.The tipping point where the VF values started to sharply decrease as a function of BMO-MRW measurements was estimated and the slopes above and below this tipping point were compared.RESULTS：A 25.9% global BMO-MRW loss from normative value was required for the VF loss to be detectable.Sectorally,substantial BMO-MRW thinning in inferotemporal sector（33.1%） and relatively less BMO-MRW thinning in the superotemporal sector（8.9%） were necessary for the detection of the VF loss.Beyond the tipping point,the slopes were close to zero throughout all of the sectors and the VF loss was unrelated to the BMO-MRW loss.The VF loss was related to the BMO-MRW loss below the tipping point.The difference between the two slopes was statistically significant（P≤0.002）.CONCLUSION：Substantial BMO-MRW loss appears to be necessary for VF loss to be detectable in patients with open angle glaucoma with standard achromatic perimetry.展开更多
AIM: To compare the diagnostic ability of glaucoma parameters measured by the optical coherence tomography(OCT) in normal, preperimetric glaucoma(PPG) and perimetric glaucoma(PG) patients. METHODS: This cross-sectiona...AIM: To compare the diagnostic ability of glaucoma parameters measured by the optical coherence tomography(OCT) in normal, preperimetric glaucoma(PPG) and perimetric glaucoma(PG) patients. METHODS: This cross-sectional observational study includes 127 eyes of 127 subjects. Patients were divided into PPG(51 eyes), PG(46 eyes), and normal controls(30 eyes) based on clinical optic disc assessment and Humphrey visual field changes. The Heidelberg Spectralis OCT machine using Glaucoma Module Premium Edition software was used to measure the retinal nerve fiber layer(RNFL) and Bruch’s membrane opening-minimum rim width(BMO-MRW) to assess the optic nerve head and ganglion cell layer(GCL) thickness in the macula. RESULTS: RNFL, MRW, and GCL thickness were all significantly thinner in PG compared to PPG and the normal group. The BMO-MRW parameters showed better specificity(>70%) at 90% specificity compared to both RNFL and GCL parameters to discriminate normal, PPG, and PG patients. All BMO-MRW parameters showed higher area under curves(AUC) compared to RNFL and GCL parameters with the highest AUC observed in the superotemporal sector of the BMO-MRW(AUC=0.819 and and 0.897 between normal and PPG and PG groups respectively).CONCLUSION: While the BMO-MRW best discriminates PPG and PG against normal eyes, GCL parameters poorly differentiate the three groups.展开更多
Background:Optic nerve head measurements extracted from optical coherence tomography(OCT)show promise for monitoring clinical conditions with elevated optic nerve heads.The aim of this study is to compare reliability ...Background:Optic nerve head measurements extracted from optical coherence tomography(OCT)show promise for monitoring clinical conditions with elevated optic nerve heads.The aim of this study is to compare reliability within and between raters and between image acquisition devices of optic nerve measurements derived from OCT scans in eyes with varying degrees of optic nerve elevation.Methods:Wide angle line scans and narrow angle radial scans through optic nerve heads were obtained using three spectral domain(SD)OCT devices on 5 subjects(6 swollen optic nerves,4 normal optic nerves).Three raters independently semi-manually segmented the internal limiting membrane(ILM)and Bruch’s membrane(BM)on each scan using customized software.One rater segmented each scan twice.Segmentations were qualitatively and quantitatively compared.Inter-rater,intra-rater and inter-device reliability was assessed for the optic nerve cross sectional area calculated from the ILM and BM segmentations using intraclass correlation coefficients and graphical comparison.Results:Line scans from all devices were qualitatively similar.Radial scans for which frame rate could not be adjusted were of lower quality.Intra-rater reliability for segmentation and optic nerve cross sectional area was better than inter-rater reliability,which was better than inter-device reliability,though all ICC exceeded 0.95.Reliability was not impacted by the degree of optic nerve elevation.Conclusions:SD-OCT devices acquired similar quality scans of the optic nerve head,with choice of scan protocol affecting the quality.For image derived markers,variability between devices was greater than that attributable to inter and intra-rater differences.展开更多
Age-related macular degeneration(AMD)is a progressive retinal disease,which is the leading cause of blindness in western countries.There is an urgency to establish new therapeutic strategies that could prevent or dela...Age-related macular degeneration(AMD)is a progressive retinal disease,which is the leading cause of blindness in western countries.There is an urgency to establish new therapeutic strategies that could prevent or delay the progression of AMD more efficiently.Until now,the pathogenesis of AMD has remained unclear,limiting the development of the novel therapy.Bruch’s membrane(BM)goes through remarkable changes in AMD,playing a significant role during the disease course.The main aim of this review is to present the crucial processes that occur at the level of BM,with special consideration of the lipid accumulation and protein modifications.Besides,some therapies targeted at these molecules and the construction of BM in tissue engineering of retinal pigment epithelium(RPE)cells transplantation were listed.Hopefully,this review may provide a reference for researchers engaged in pathogenesis or management on AMD.展开更多
Background:To investigate the microstructural features of parapapillary gamma zone and beta zone and their relationship with three-dimensional optic disc shape in non-myopic eyes.Methods:This cross-sectional study inc...Background:To investigate the microstructural features of parapapillary gamma zone and beta zone and their relationship with three-dimensional optic disc shape in non-myopic eyes.Methods:This cross-sectional study included 62 non-myopic eyes with parapapillary gamma or beta zone and 70 control eyes.On the spectral domain optical coherent tomography(SD-OCT)images,we measured the area of gamma zone and beta zone,the length of border tissue,and related disc parameters.The disc ovality index,disc rotation degrees around three axes,Bruch’s membrane opening(BMO)ovality ratio were calculated based on the SD-OCT images.Results:The parapapillary gamma zone composed by externally oblique border tissue was found in inferior,nasal and temporal quadrants of the non-myopic eyes.The presence of gamma zone in non-myopic eyes was correlated with smaller disc ovality index,larger rotation degree around vertical and horizontal axes,and larger BMO ovality ratio(P<0.001).Compared with the non-temporal gamma zone group,eyes with temporal gamma zone had a longer axial length and rotated more around vertical axes(P<0.001).Multivariate analysis showed that the area of gamma zone was correlated with the disc ovality index(P<0.001).The presence and area of beta zone was correlated with age(P<0.01).Conclusions:In non-myopic eyes,the parapapillary gamma zone composed by external oblique border tissue was significantly associated with the disc ovality and disc rotations around vertical and horizontal axes.From a biomechanical perspective,parapapillary gamma zone may contribute to the optic disc stability in association with the structure of BMO.展开更多
文摘Background:The goal of this review is to summarize structural and anatomical changes associated with high myopia.Main text:Axial elongation in myopic eyes is associated with retinal thinning and a reduced density of retinal pigment epithelium(RPE)cells in the equatorial region.Thickness of the retina and choriocapillaris and RPE cell density in the macula are independent of axial length.Choroidal and scleral thickness decrease with longer axial length in the posterior hemisphere of the eye,most marked at the posterior pole.In any eye region,thickness of Bruch’s membrane(BM)is independent of axial length.BM opening,as the inner layer of the optic nerve head layers,is shifted in temporal direction in moderately elongated eyes(axial length<26.5 mm).It leads to an overhanging of BM into the intrapapillary compartment at the nasal optic disc side,and to an absence of BM at the temporal disc border.The lack of BM at the temporal disc side is the histological equivalent of parapapillary gamma zone.Gamma zone is defined as the parapapillary region without BM.In highly myopic eyes(axial length>26.5 mm),BM opening enlarges with longer axial length.It leads to a circular gamma zone.In a parallel manner,the peripapillary scleral flange and the lamina cribrosa get longer and thinner with longer axial length in highly myopic eyes.The elongated peripapillary scleral flange forms the equivalent of parapapillary delta zone,and the elongated lamina cribrosa is the equivalent of the myopic secondary macrodisc.The prevalence of BM defects in the macular region increases with longer axial length in highly myopic eyes.Scleral staphylomas are characterized by marked scleral thinning and spatially correlated BM defects,while thickness and density of the choriocapillaris,RPE and BM do not differ markedly between staphylomatous versus non-staphylomatous eyes in the respective regions.Conclusions:High axial myopia is associated with a thinning of the sclera and choroid posteriorly and thinning of the retina and RPE density in the equator
文摘Purpose: The primary aim of this paper is to design, create, and improve functional and artificial Bruch’s membranes (BM) using bioengineering techniques, which can be applied in the treatment of maculopathies by supporting the growth and maintenance of retinal pigment epithelium (RPE) cells, thereby potentially enabling subretinal implantation in patients. Methods: We fabricated by electrospinning ultrathin 3D nanofibrous membranes from Polycaprolactone (PCL), and different concentrations of gelatin (5%, 15% and 30%). ARPE-19 cells were seeded onto these artificial membranes. MTT assays were performed in order to evaluate ARPE-19 cell viability and cytotoxicity. IF assays were realized to observe the ARPE-19 cells onto each membrane. Ultrastructure of the modified Bruch’s membrane and ARPE-19 morphology after 25 days of culture were studied with transmission and scanning electron microscopy. To evaluate expression changes in markers of ARPE-19 (RPE65 and ZO-1) qRT-PCR assays were realized. Data from three independent experiments were pooled and expressed as the mean SD. A confidence level of P 0.05 was considered to be statistically significant. Results ARPE-19 cells grew on PCL/Gelatin membranes mainly in PCL/30% gelatin combination, which had not cytotoxic effect. RPE65/cytokeratin-18/ and actin-positive ARPE-19 cells formed a correctly orientated monolayer of polygonal cells with morphological polarity. The apical cell surfaces exhibited abundant protruding microfolds. Moreover, zones of polygonal border look as if ARPE-19 cells fused among, suggesting the presence of tight junctions. The expression of RPE65 and ZO-1 was unchanged. Conclusions: PCL/30% Gelatine membranes may imitate the natural BM to such extent that they support RPE-cells and exhibited RPE-like morphology. The engineering of a human RPE monolayer with these artificial BM, emulating the in vivo retina, arouse their potential subretinal implantation in patients with wet age-related macular degeneration (AMD) where there is a rupture of the
文摘AIM: To compare the ocular fundus features of highly myopic eyes with and without macular Bruch’s membrane(BM) defects and investigate the associations between macular BM defects and other myopic lesions.METHODS: This retrospective, observational case series included 262 eyes(139 patients) with high myopia(HM) refractive error ≥-6.0 diopters(D) or axial length ≥26.5 mm from March 2019 to December 2019.The patients underwent a comprehensive ophthalmic examination, including sweptsource optical coherence tomography(SS-OCT).The features of macular BM defects and other ocular fundus lesions were examined in OCT images.RESULTS: Totally 51 eyes(19.5%) were detected with macular BM defects, which were characterized by a lack of BM, retinal pigment epithelium(RPE), and an almost complete loss of photoreceptors or choriocapillaris.Eyes with macular BM defects had worse best-corrected visual acuity(BCVA) than those without(P<0.001).Dome-shaped macula(DSM, P=0.042), retinal cysts(P=0.006), choroidal neovascularization(CNV, P<0.001), choroidal defects and abnormality(P=0.003), scleral defects(P=0.015), scleral deformation(P=0.005), posterior staphyloma(P=0.011), and perforating vessels(P<0.001) occurred more frequently in eyes with macular BM defects.In multivariate analysis, the presence of macular BM defects remained the significant association with presence of DSM(P=0.013), scleral defects(P=0.015), posterior staphyloma(P=0.001), perforating vessels(P<0.001) and CNV(P=0.004).CONCLUSION: Macular BM defects has a prevalence of approximately 20% in HM and it has tight association with other myopic fundus lesions.BM might be crucial in the pathogenesis of myopic fundus lesions due to its biomechanical function.A comprehensive understanding of BM’s role is useful for further researches about myopic lesions.
基金supported by the Ministry of Science and Innovation of Spain,"Instituto de Salud CarlosⅢ","Fon do de Investigacion Sanitaria" (PI19/00265)funds FEDER"Una manera de hacer Europa" (to BM)。
文摘Age-related macular degeneration,a multifactorial inflammatory degenerative retinal disease,ranks as the leading cause of blindness in the elderly.Strikingly,there is a scarcity of curative therapies,especially for the atrophic advanced form of age-related macular degeneration,likely due to the lack of models able to fully recapitulate the native structure of the outer blood retinal barrier,the prime to rget tissue of age-related macular degeneration.Standard in vitro systems rely on 2D monocultures unable to adequately reproduce the structure and function of the outer blood retinal barrier,integrated by the dynamic interaction of the retinal pigment epithelium,the Bruch's membrane,and the underlying choriocapillaris.The Bruch's membrane provides structu ral and mechanical support and regulates the molecular trafficking in the outer blood retinal barrier,and therefo re adequate Bruch's membrane-mimics are key for the development of physiologically relevant models of the outer blood retinal barrie r.In the last years,advances in the field of biomaterial engineering have provided novel approaches to mimic the Bruch's membrane from a variety of materials.This review provides a discussion of the integrated properties and function of outer blood retinal barrier components in healt hy and age-related macular degeneration status to understand the requirements to adequately fabricate Bruch's membrane biomimetic systems.Then,we discuss novel materials and techniques to fabricate Bruch's membrane-like scaffolds for age-related macular degeneration in vitro modeling,discussing their advantages and challenges with a special focus on the potential of Bruch's membrane-like mimics based on decellularized tissue.
文摘AIM：To evaluate and compare structural optical coherence tomography（OCT）-based parameters,such as Bruch’s membrane opening-minimum rim width（BMO-MRW）,and retinal nerve fiber layer（RNFL）thickness in glaucoma patients with visual field（VF）defects,and to correlate both to mean deviation（MD）values of obtained standard achromatic perimetry（SAP）examinations.METHODS：Patients with glaucoma and glaucomatous VF defects were enrolled in this prospective study and compared to age-matched healthy individuals.All study participants underwent a full ophthalmic examination and VF testing with SAP.Peripapillary RNFL thickness and BMO-MRW were acquired with SD-OCT.Correlation analyses between obtained global functional and global as well as sectorial structural parameters were calculated.RESULTS：A consecutive series of 30 glaucomatous right eyes of 30 patients were included and compared to 36healthy right eyes of 36 individuals in the control group.Global MD of values correlated significantly with global RNFL（Pearson corr.coeff：0.632,P=0.001）and global BMO-MRW（Pearson corr.coeff：0.746,P〈0.001）values in the glaucoma group.Global MD and sectorial RNFL or BMO-MRW values correlated less significantly.In the control group,MD values did not correlate with RNFL or BMO-MRW measurements.A subgroup analysis of myopic patients（〉4 diopters）within the glaucoma group（n=6）revealed a tendency for higher correlations between MD and BMO-MRW than MD and RNFL measurements.CONCLUSION：In a clinical setting,RNFL thickness and BMO-MRW correlate similarly with global VF sensitivity in glaucoma patients with BMO-MRW showing higher correlations in myopic glaucoma patients.
文摘AIM:To assess the agreement of optical coherence tomography(OCT)algorithm-based retinal pigment epithelium–Bruch’s membrane complex volume(RBV)with fundus photograph-based age-related macular degeneration(AMD)grading.METHODS:Digital color fundus photographs(CFPs)and spectral domain OCT images were acquired from 96 elderly subjects.CFPs were graded according to Age-Related Eye Disease Study(AREDS)classification.OCT image segmentation and RBV data calculation were done with OrionTM software.Univariate and multivariate analyses were performed to find out whether AMD lesion features associated with higher RBVs.RESULTS:RBV correlated with AMD grading(rs=0.338,P=0.001),the correlation was slightly stronger in early AMD(n=52;rs=0.432,P=0.001).RBV was higher in subjects with early AMD compared with those with no AMD lesions evident in fundus photographs(1.05±0.20 vs 0.96±0.13 mm3,P=0.023).In multivariate analysis higher RBVs were associated significantly with higher total drusen(β=0.388,P=0.027)and pigmentation areas(β=0.319,P=0.020)in fundus photographs,whereas depigmentation area(β=-0.295,P=0.015)associated with lower RBV.CONCLUSION:RBV correlate with AMD grading status,with a stronger association in patients with moderate,non-late AMD grades.This effect is driven mostly by lesions with drusen or pigmentation.Lesions with depigmentation tend to have lower values.RBV is more comprehensive measurement of the key area of AMD pathogenesis,compared to sole drusen volume analysis.RBV measurements are independent on grader variations and offer a possibility to quantify early and middle grade AMD lesions in a research setting,but may not substitute fundus photograph-based grading in the whole range of AMD spectrum.
文摘Background:The goal of this review is to summarize structural and anatomical changes associated with high myopia.Main text:Axial elongation in myopic eyes is associated with retinal thinning and a reduced density of retinal pigment epithelium(RPE)cells in the equatorial region.Thickness of the retina and choriocapillaris and RPE cell density in the macula are independent of axial length.Choroidal and scleral thickness decrease with longer axial length in the posterior hemisphere of the eye,most marked at the posterior pole.In any eye region,thickness of Bruch's membrane(BM)is independent of axial length.BM opening,as the inner layer of the optic nerve head layers,is shifted in temporal direction in moderately elongated eyes(axial length<26.5 mm).It leads to an overhanging of BM into the intrapapillary compartment at the nasal optic disc side,and to an absence of BM at the temporal disc border.The lack of BM at the temporal disc side is the histological equivalent of parapapillary gamma zone.Gamma zone is defined as the parapapillary region without BM.In highly myopic eyes(axial length>26.5 mm),BM opening enlarges with longer axial length.It leads to a circular gamma zone.In a parallel manner,the peripapillary scleral flange and the lamina cribrosa get longer and thinner with longer axial length in highly myopic eyes.The elongated peripapillary scleral flange forms the equivalent of parapapillary delta zone,and the elongated lamina cribrosa is the equivalent of the myopic secondary macrodisc.The prevalence of BM defects in the macular region increases with longer axial length in highly myopic eyes.Scleral staphylomas are characterized by marked scleral thinning and spatially correlated BM defects,while thickness and density of the choriocapillaris,RPE and BM do not differ markedly between staphylomatous versus non-staphylomatous eyes in the respective regions.Conclusions:High axial myopia is associated with a thinning of the sclera and choroid posteriorly and thinning of the retina and reduction of RPE density in
文摘AIM：To determine the Bruch＇s membrane opening-minimum rim width（BMO-MRW） tipping point where corresponding visual field（VF） damages become detectable.METHODS：A total of 85 normal subjects and 83 glaucoma patients（one eye per participant） were recruited for the study.All of the patients had VF examinations and spectral-domain optical coherence tomography to measure the BMO-MRW.Total deviation values for 52 VF points were allocated to the corresponding sector according to the Garway-Heath distribution map.To evaluate the relationship between VF loss and BMOMRW measurements,a ＂broken-stick＂ statistical model was used.The tipping point where the VF values started to sharply decrease as a function of BMO-MRW measurements was estimated and the slopes above and below this tipping point were compared.RESULTS：A 25.9% global BMO-MRW loss from normative value was required for the VF loss to be detectable.Sectorally,substantial BMO-MRW thinning in inferotemporal sector（33.1%） and relatively less BMO-MRW thinning in the superotemporal sector（8.9%） were necessary for the detection of the VF loss.Beyond the tipping point,the slopes were close to zero throughout all of the sectors and the VF loss was unrelated to the BMO-MRW loss.The VF loss was related to the BMO-MRW loss below the tipping point.The difference between the two slopes was statistically significant（P≤0.002）.CONCLUSION：Substantial BMO-MRW loss appears to be necessary for VF loss to be detectable in patients with open angle glaucoma with standard achromatic perimetry.
基金Supported by Norshamsiah Md Din receives funding from the UKMMC Fundamental Research Grant (No.FF-2017-169)Yusof AMZ receives a Masters scholarship funded by the Government of Malaysia。
文摘AIM: To compare the diagnostic ability of glaucoma parameters measured by the optical coherence tomography(OCT) in normal, preperimetric glaucoma(PPG) and perimetric glaucoma(PG) patients. METHODS: This cross-sectional observational study includes 127 eyes of 127 subjects. Patients were divided into PPG(51 eyes), PG(46 eyes), and normal controls(30 eyes) based on clinical optic disc assessment and Humphrey visual field changes. The Heidelberg Spectralis OCT machine using Glaucoma Module Premium Edition software was used to measure the retinal nerve fiber layer(RNFL) and Bruch’s membrane opening-minimum rim width(BMO-MRW) to assess the optic nerve head and ganglion cell layer(GCL) thickness in the macula. RESULTS: RNFL, MRW, and GCL thickness were all significantly thinner in PG compared to PPG and the normal group. The BMO-MRW parameters showed better specificity(>70%) at 90% specificity compared to both RNFL and GCL parameters to discriminate normal, PPG, and PG patients. All BMO-MRW parameters showed higher area under curves(AUC) compared to RNFL and GCL parameters with the highest AUC observed in the superotemporal sector of the BMO-MRW(AUC=0.819 and and 0.897 between normal and PPG and PG groups respectively).CONCLUSION: While the BMO-MRW best discriminates PPG and PG against normal eyes, GCL parameters poorly differentiate the three groups.
基金National Institutes of Health K23 EY024345(to Heather Moss)P30026877(to the Stanford Department of Ophthalmology)an unrestricted grant from Research to Prevent Blindness to the Stanford Department of Ophthalmology.
文摘Background:Optic nerve head measurements extracted from optical coherence tomography(OCT)show promise for monitoring clinical conditions with elevated optic nerve heads.The aim of this study is to compare reliability within and between raters and between image acquisition devices of optic nerve measurements derived from OCT scans in eyes with varying degrees of optic nerve elevation.Methods:Wide angle line scans and narrow angle radial scans through optic nerve heads were obtained using three spectral domain(SD)OCT devices on 5 subjects(6 swollen optic nerves,4 normal optic nerves).Three raters independently semi-manually segmented the internal limiting membrane(ILM)and Bruch’s membrane(BM)on each scan using customized software.One rater segmented each scan twice.Segmentations were qualitatively and quantitatively compared.Inter-rater,intra-rater and inter-device reliability was assessed for the optic nerve cross sectional area calculated from the ILM and BM segmentations using intraclass correlation coefficients and graphical comparison.Results:Line scans from all devices were qualitatively similar.Radial scans for which frame rate could not be adjusted were of lower quality.Intra-rater reliability for segmentation and optic nerve cross sectional area was better than inter-rater reliability,which was better than inter-device reliability,though all ICC exceeded 0.95.Reliability was not impacted by the degree of optic nerve elevation.Conclusions:SD-OCT devices acquired similar quality scans of the optic nerve head,with choice of scan protocol affecting the quality.For image derived markers,variability between devices was greater than that attributable to inter and intra-rater differences.
文摘Age-related macular degeneration(AMD)is a progressive retinal disease,which is the leading cause of blindness in western countries.There is an urgency to establish new therapeutic strategies that could prevent or delay the progression of AMD more efficiently.Until now,the pathogenesis of AMD has remained unclear,limiting the development of the novel therapy.Bruch’s membrane(BM)goes through remarkable changes in AMD,playing a significant role during the disease course.The main aim of this review is to present the crucial processes that occur at the level of BM,with special consideration of the lipid accumulation and protein modifications.Besides,some therapies targeted at these molecules and the construction of BM in tissue engineering of retinal pigment epithelium(RPE)cells transplantation were listed.Hopefully,this review may provide a reference for researchers engaged in pathogenesis or management on AMD.
基金Supported by the grants from Science and Technology Commission of Shanghai Municipality(No.16411962000)The sponsor or funding organization had no role in the design or conduct of this research.
文摘Background:To investigate the microstructural features of parapapillary gamma zone and beta zone and their relationship with three-dimensional optic disc shape in non-myopic eyes.Methods:This cross-sectional study included 62 non-myopic eyes with parapapillary gamma or beta zone and 70 control eyes.On the spectral domain optical coherent tomography(SD-OCT)images,we measured the area of gamma zone and beta zone,the length of border tissue,and related disc parameters.The disc ovality index,disc rotation degrees around three axes,Bruch’s membrane opening(BMO)ovality ratio were calculated based on the SD-OCT images.Results:The parapapillary gamma zone composed by externally oblique border tissue was found in inferior,nasal and temporal quadrants of the non-myopic eyes.The presence of gamma zone in non-myopic eyes was correlated with smaller disc ovality index,larger rotation degree around vertical and horizontal axes,and larger BMO ovality ratio(P<0.001).Compared with the non-temporal gamma zone group,eyes with temporal gamma zone had a longer axial length and rotated more around vertical axes(P<0.001).Multivariate analysis showed that the area of gamma zone was correlated with the disc ovality index(P<0.001).The presence and area of beta zone was correlated with age(P<0.01).Conclusions:In non-myopic eyes,the parapapillary gamma zone composed by external oblique border tissue was significantly associated with the disc ovality and disc rotations around vertical and horizontal axes.From a biomechanical perspective,parapapillary gamma zone may contribute to the optic disc stability in association with the structure of BMO.
