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Inner Segment Remodeling and Mitochondrial Translocation in Cone Photoreceptors in Age-Related Macular Degeneration With Outer Retinal Tubulation
摘要： PURPOSE. To quantify impressions of mitochondrial translocation in degenerating cones and to determine the nature of accumulated material in the subretinal space with apparent inner segment (IS)-like features by examining cone IS ultrastructure. METHODS. Human donor eyes with advanced age-related macular degeneration (AMD) were screened for outer retinal tubulation (ORT) in macula-wide, high-resolution digital sections. Degenerating cones inside ORT (ORT cones) and outside ORT (non-ORT cones) from AMD eyes and unaffected cones in age-matched control eyes were imaged using transmission electron microscopy. The distances of mitochondria to the external limiting membrane (ELM), cone IS length, and cone IS width at the ELM were measured. RESULTS. Outer retinal tubulation and non-ORT cones lose outer segments (OS), followed by shortening of IS and mitochondria. In non-ORT cones, IS broaden. Outer retinal tubulation and non-ORT cone IS myoids become undetectable due to mitochondria redistribution toward the nucleus. Some ORT cones were found lacking IS and containing mitochondria in the outer fiber (between soma and ELM). Unlike long, thin IS mitochondria in control cones, ORT and non-ORT IS mitochondria are ovoid or reniform. Shed IS, some containing mitochondria, were found in the subretinal space. CONCLUSIONS. In AMD, macula cones exhibit loss of detectable myoid due to IS shortening in addition to OS loss, as described. Mitochondria shrink and translocate toward the nucleus. As reflectivity sources, translocating mitochondria may be detectable using in vivo imaging to monitor photoreceptor degeneration in retinal disorders. These results improve the knowledge basis for interpreting high-resolution clinical retinal imaging.
关键词： ellipsoid,outer retinal tubulation,age-related macular degeneration,histology,photoreceptors,cones,myoid,transmission electron microscopy,Müller cells
更新于2025-09-10 09:29:36
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Functional optical coherence tomography of retinal photoreceptors
摘要： Age-related macular degeneration (AMD) is the leading cause of severe vision loss and legal blindness. It is known that retinal photoreceptors are the primary target of AMD. Therefore, a reliable method for objective assessment of photoreceptor function is needed for early detection and reliable treatment evaluation of AMD and other eye diseases such as retinitis pigmentosa that are known to cause photoreceptor dysfunctions. Stimulus-evoked intrinsic optical signal (IOS) changes promise a unique opportunity for objective assessment of physiological function of retinal photoreceptor and inner neurons. Instead of a comprehensive review, this mini-review is to provide a brief summary of our recent in vitro and in vivo optical coherence tomography (OCT) studies of stimulus-evoked IOS changes in animal retinas. By providing excellent axial resolution to differentiate individual retinal layers, depth-resolved OCT revealed rapid IOS response at the photoreceptor outer segment. The fast photoreceptor-IOS occurred almost right away ((cid:1) 2 ms) after the onset of retinal stimulation, differentiating itself from slow IOS changes correlated with inner neural and hemodynamic changes. Further development of the functional IOS instruments and retinal stimulation protocols may provide a feasible solution to pursue clinical application of functional IOS imaging for objective assessment of human photoreceptors.
关键词： intrinsic optical signal,photoreceptors,Optical coherence tomography,age-related macular degeneration
更新于2025-09-10 09:29:36
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New insight into the role of the complement in the most common types of retinopathy-current literature review
摘要： Pathological neovascularisation, which is a critical component of diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR) and retinopathy of prematurity (ROP), is a frequent cause of compromised vision or blindness. Researchers continuously investigate the role of the complement system in the pathogenesis of retinopathy. Studies have confirmed the role of factors H and I in the development of AMD, and factors H and B in the development of DR. Other components, such as C2, C3, and C5, have also been considered. However, findings on the involvement of the complement system in the pathogenesis of ROP are still inconclusive. This paper presents a review of the current literature data, pointing to the novel results and achievements from research into the role of complement components in the development of retinopathy. There is still a need to continue research in new directions, and to gather more detailed information about this problem which will be useful in the treatment of these diseases.
关键词： diabetic retinopathy,age-related macular degeneration,factors of the complement system,retinopathy of prematurity,single nucleotide polymorphism
更新于2025-09-10 09:29:36
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Foveal structure during the induction phase of anti-vascular endothelial growth factor therapy for occult choroidal neovascularization in age-related macular degeneration
摘要： Purpose: To evaluate the efficacy of monthly injections of aflibercept and ranibizumab on foveal structure after three months, for the treatment of occult choroidal neovascularization (CNV) in age-related macular degeneration (AMD). Methods: We retrospectively studied 103 eyes with treatment-na?ve neovascular AMD with occult and no classic CNV. Seventy-four of 103 eyes were treated with ranibizumab (intravitreal ranibizumab injection [IVR] group); 29 eyes were treated with aflibercept (intravitreal aflibercept injection [IAI] group). The best-corrected visual acuity and the retinal and choroidal structure at the fovea were evaluated using optical coherence tomography. Results: The total foveal thickness, the height of serous retinal detachments, and subfoveal choroidal thickness were compared with baseline, and the incidence of retinal pigment epithelial elevation significantly decreased in the IAI group compared with the IVR group. In contrast, the thickness of the sensory retina at the fovea significantly decreased in the IVR group when compared with the IAI group. The logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity improved more significantly in the IVR group (?0.085±0.164) than in the IAI group (?0.020±0.125) at 3 months (P=0.017). Conclusion: After intravitreal injection, aflibercept more rapidly reduced subretinal fluid and subfoveal choroidal thickness. In contrast, ranibizumab decreased the sensory retinal thickness compared with aflibercept. The responses of the retinal and choroidal tissue to these anti-VEGF agents may be different during the induction phase for eyes with occult CNV secondary to neovascular AMD.
关键词： occult,neovascular age-related macular degeneration,outer nuclear layer,aflibercept,retinal thickness,ranibizumab
更新于2025-09-10 09:29:36
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[IEEE 2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) - Honolulu, HI, USA (2018.7.18-2018.7.21)] 2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) - Automatic Detection of Preferred Retinal Locus (PRL) for Low Vision Rehabilitation using Oculometrics Analysis*
摘要： Low vision rehabilitation is an important step towards individuals with Age-related macular degeneration (AMD) regaining useful functional vision and quality of life. One of the key steps in low vision rehabilitation is the determination of the preferred retinal locus (PRL). Currently, localization of PRL is performed manually though the guidance of a low vision therapist and the process is highly time-consuming, labour-intensive and subjective. In this paper, we present an automated system to objectively and accurately locate an individual’s PRL with the aid of gaze tracking technology. We also propose a graph-based method for false fixation detection to improve the system robustness. We validated the reliability of the system by using eye tracking technology to simulate central vision loss on people with normal vision. Experimental results show the potential use of eye tracking in detecting PRL for low vision rehabilitation.
关键词： Preferred retinal locus,Eye tracking technology,Low vision rehabilitation,False fixation detection,Age-related macular degeneration
更新于2025-09-10 09:29:36
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Initial Utilization of Aflibercept in Exudative Age-related Macular Degeneration
摘要： Purpose: Intravitreal aflibercept, a fusion protein with high affinity for vascular endothelial growth factor, offers an alternative treatment for exudative age-related macular degeneration. Preclinical studies and early and late phase clinical trials suggest that aflibercept’s high binding affinity may impart greater durability of activity and increased efficacy compared to ranibizumab or bevacizumab. Methods: A total of 266 eyes of 249 patients with exudative age-related macular degeneration who received aflibercept after treatment with bevacizumab and/or ranibizumab were included in a retrospective review. Mean central subfoveal thickness on spectral-domain optical coherence tomography and mean logarithm of the minimal angle of resolution (logMAR) visual acuity were calculated at 1, 3, 6, and 12 months after the first aflibercept injection. Subgroup analyses were performed in eyes receiving at least 5 bevacizumab and/or ranibizumab injections in the 6 months prior to aflibercept and in eyes receiving at least 10 injections in the 12 months prior to aflibercept. Results: Eyes received an average of 14.7 (range 1-43) ranibizumab and/or bevacizumab treatments prior to initiation of aflibercept therapy. The mean central subfoveal thickness decreased from 300 to 275 μm at 1 month (p<0.001) and was maintained at 6 months. Mean logMAR visual acuity improved from 0.60 (Snellen equivalent 20/80) to 0.54 (20/70, p = 0.01) at 1 month and was stable at 0.55 at 6 months (Snellen equivalent 20/70, p = 0.11, n = 251). In 82 eyes receiving at least 5 injections in the 6 months prior to aflibercept treatment (average of 18.1 injections total), the central subfoveal thickness improved from 296 to 279 μm at 1 month (p<0.0001) and was maintained at 6 months (p<0.0001). Visual acuity did not change (0.48 [20/61] at 1 month compared to baseline, 0.49 [20/62], p = 0.634, and at 6 months 0.51 [20/65], p = 0.601). In 50 eyes receiving at least 10 injections in the 12 months prior to aflibercept treatment (average of 21.8 injections total), the mean central subfoveal thickness decreased by 17 μm at 1 month (p = 0.0007) and was maintained at 6 months (p = 0.013). Again, visual acuity did not change (0.46 [20/56] at 1 month, baseline 0.44 [20/56], p = 0.547, and 0.50 [20/63] at 6 months, p = 0.2445). Conclusions: Aflibercept is a valuable treatment alternative in patients previously treated with bevacizumab and/or ranibizumab injections. Stability of visual acuity and anatomic improvement on spectral-domain optical coherence tomography were observed after initiation of aflibercept treatment in those previously treated with ranibizumab and/or bevacizumab injections every 4-6 weeks.
关键词： Ranibizumab,Age-related macular degeneration,Choroidal neovascularization,Aflibercept,Bevacizumab
更新于2025-09-10 09:29:36
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Optical coherence tomography angiography (OCTA) flow speed mapping technology for retinal diseases
摘要： Introduction: Optical coherence tomography angiography (OCTA) is a noninvasive imaging modality for depth-resolved visualization of retinal vasculature. Angiographic data couples with structural data to generate a cube scan, from which en-face images of vasculature can be obtained at various axial positions. OCTA has expanded understanding of retinal vascular disorders and has primarily been used for qualitative analysis. Areas covered: Recent studies have explored the quantitative properties of OCTA, which would allow for objective assessment and follow-up of retinal pathologies. Various quantitative metrics have been developed, such as foveal avascular zone area and vessel density. However, quantitative assessment of the characteristics of retinal blood flow remains limited, as OCTA provides an image depicting either the presence or absence of flow at a particular region without information of relative velocities. The development of variable interscan time analysis (VISTA) overcomes this limitation. The VISTA algorithm generates a color-coded map of relative blood flow speeds. VISTA has already demonstrated utility in furthering our understanding of various retinal pathologies, such as geographic atrophy, choroidal neovascularization, aneurysmal type 1 neovascularization, and diabetic retinopathy. Expert commentary: VISTA, an OCTA flow speed mapping technique, may have a role in developing the utility of OCTA as a screening tool.
关键词： flow speed mapping,diabetic retinopathy,age-related macular degeneration,VISTA,quantitative OCTA,OCTA,Optical coherence tomography angiography,variable interscan time analysis,OCT
更新于2025-09-10 09:29:36
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Optical coherence tomography angiography in exudative age-related macular degeneration: a predictive model for treatment decisions
摘要： Aims To evaluate on optical coherence tomography angiography (OCT-A), the predictive role of different qualitative findings of choroidal neovascularisations (CNV) in assessing the status of exudative age-related macular degeneration (eAMD) and to develop a potential model to predict the CNV activity. Methods Retrospective review of the multimodal imaging records of patients with eAMD obtained during treatment for type 1 or type 2 CNV. The qualitative analysis of CNVs on OCT angiograms assessed the presence or absence of tiny branching vessels, loops, peripheral anastomotic arcades and choriocapillaris hypointense halo. These findings were then correlated with those of structural OCT scans. A score forecast was built and validated. results One hundred and twenty-six eAMD eyes were enrolled in the study. Exudation was observed in 90 eyes (71%) on structural OCT. The qualitative OCT-A analysis revealed: tiny branching vessels in 82.5% of the cases, vascular loops in 81.7%, peripheral anastomotic arcades in 66.7% and choriocapillaris hypointense halo in 54.8%. In the univariate analysis, each OCT-A parameter showed a statistically significant correlation with exudation on structural OCT (p<0.001). The overall analysis demonstrated a sensitivity of 96.7% and a positive predictive value of 87.9%. In the multivariate analysis, a model with four criteria predicted an exudative lesion in 97.6% of cases and one with two criteria (tiny branching vessels and peripheral anastomotic arcades) in 71.2%. Conclusions The presence of tiny branching vessels and a peripheral anastomotic arcade appears to predict the lesion activity with a good accuracy and the model based on four criteria enables optimal decisions regarding retreatment in eAMD.
关键词： exudative age-related macular degeneration,optical coherence tomography angiography,treatment decisions,choroidal neovascularisations,predictive model
更新于2025-09-10 09:29:36
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Macular Atrophy Development and Subretinal Drusenoid Deposits in Anti-Vascular Endothelial Growth Factor Treated Age-Related Macular Degeneration
摘要： PURPOSE. To explore the association between presence of subretinal drusenoid deposits (SDD) at baseline in eyes with neovascular age-related macular degeneration (nAMD) with the development of macular atrophy (MA) during anti-vascular endothelial growth factor (VEGF) therapy. METHODS. There were 74 eyes without pre-existing MA receiving anti-VEGF therapy for nAMD for 2 years or longer analyzed. At least two image modalities that included spectral-domain optical coherence tomography, near-infrared re?ectance, ?uorescein angiography, and color fundus photos were used to assess for SDD presence, phenotype (dot and ribbon), and location, neovascularization type, and MA. Logistic regression models using generalized estimating equations assessed the association between SDD and the development of MA adjusting for age, neovascularization type, and choroidal thickness. RESULTS. SDD were present in 46 eyes (63%) at baseline. MA developed in 38 eyes (51%) during the mean of 4.7 6 1.2 years of follow-up. Compared with eyes without SDD, those with SDD at baseline were 3.0 times (95% con?dence interval [CI] 1.1–8.5, P ? 0.0343) more likely to develop MA. Eyes with SDD present in the inferior macula and inferior extramacular ?elds at baseline were 3.0 times and 6.5 times more likely to develop MA at follow-up than eyes without SDD in these locations (95% CI 1.0–8.9, P ? 0.0461 and 95% CI 1.3–32.4, P ? 0.0218, respectively). MA development was not associated with a speci?c SDD phenotype. CONCLUSIONS. MA frequently developed in eyes during anti-VEGF treatment. SDD were independently associated with MA development. The extension of SDD into the inferior fundus, particularly in the inferior extramacular ?eld, conferred higher odds of subsequent MA development.
关键词： reticular pseudodrusen,anti-VEGF,neovascular age-related macular degeneration,geographic atrophy,subretinal drusenoid deposits
更新于2025-09-10 09:29:36
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Spatial Correspondence Between Intraretinal Fluid, Subretinal Fluid, and Pigment Epithelial Detachment in Neovascular Age-Related Macular Degeneration
摘要： PURPOSE. To identify the spatial distribution of exudative features of choroidal neovascularization in neovascular age-related macular degeneration (nAMD) based on the localization of intraretinal cystoid fluid (IRC), subretinal fluid (SRF), and pigment-epithelial detachment (PED). METHODS. This retrospective cross-sectional study included spectral-domain optical coherence tomography volume scans (6 3 6 mm) of 1341 patients with treatment-na¨?ve nAMD. IRC, SRF, and PED were detected on a per-voxel basis using fully automated segmentation algorithms. Two subsets of 37 volumes each were manually segmented to validate the automated results. The spatial correspondence of components was quantified by computing proportions of IRC-, SRF-, or PED-presenting A-scans simultaneously affected by the respective other pathomorphologic components on a per-patient basis. The median across the population is reported. Odds ratios between pairs of lesions were calculated and tested for significance pixel wise. RESULTS. Automated image segmentation was successful in 1182 optical coherence tomography volumes, yielding more than 61 million A-scans for analysis. Overall, 81% of eyes showed IRC, 95% showed SRF, and 92% showed PED. IRC-presenting A-scans also showed SRF in a median 2.5%, PED in 32.9%. Of the SRF-presenting A-scans, 0.3% demonstrated IRC, 1.4% PED. Of the PED-presenting A-scans, 5.2% contained IRC, 2.0% SRF. Similar patterns were observed in the manually segmented subsets and via pixel-wise odds ratio analysis. CONCLUSIONS. Automated analyses of large-scale datasets in a cross-sectional study of 1182 patients with active treatment-na¨?ve nAMD demonstrated low spatial correlation of SRF with IRC and PED in contrast to increased colocalization of IRC and PED. These morphological associations may contribute to our understanding of functional deficits in nAMD.
关键词： subretinal fluid,age-related macular degeneration,intraretinal cystoid fluid,optical coherence tomography,automated image analysis
更新于2025-09-10 09:29:36