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BACKGROUND: Spectral-domain (SD-) optical coherence tomography (OCT) can reliably measure axonal (peripapillary retinal nerve fiber layer [pRNFL]) and neuronal (macular ganglion cell + inner plexiform layer [GCIPL]) thinning in the retina. Measurements from 2 commonly used SD-OCT devices are often pooled together in multiple sclerosis (MS) studies and clinical trials despite software and segmentation algorithm differences; however, individual pRNFL and GCIPL thickness measurements are not interchangeable between devices. In some circumstances, such as in the absence of a consistent OCT segmentation algorithm across platforms, a conversion equation to transform measurements between devices may be useful to facilitate pooling of data. The availability of normative data for SD-OCT measurements is limited by the lack of a large representative world-wide sample across various ages and ethnicities. Larger international studies that evaluate the effects of age, sex, and race/ethnicity on SD-OCT measurements in healthy control participants are needed to provide normative values that reflect these demographic subgroups to provide comparisons to MS retinal degeneration. METHODS: Participants were part of an 11-site collaboration within the International Multiple Sclerosis Visual System (IMSVISUAL) consortium. SD-OCT was performed by a trained technician for healthy control subjects using Spectralis or Cirrus SD-OCT devices. Peripapillary pRNFL and GCIPL thicknesses were measured on one or both devices. Automated segmentation protocols, in conjunction with manual inspection and correction of lines delineating retinal layers, were used. A conversion equation was developed using structural equation modeling, accounting for clustering, with healthy control data from one site where participants were scanned on both devices on the same day. Normative values were evaluated, with the entire cohort, for pRNFL and GCIPL thicknesses for each decade of age, by sex, and across racial groups using generalized estimating equation (GEE) models, accounting for clustering and adjusting for within-patient, intereye correlations. Change-point analyses were performed to determine at what age pRNFL and GCIPL thicknesses exhibit accelerated rates of decline. RESULTS: The healthy control cohort (n = 546) was 54% male and had a wide distribution of ages, ranging from 18 to 87 years, with a mean (SD) age of 39.3 (14.6) years. Based on 346 control participants at a single site, the conversion equation for pRNFL was Cirrus = -5.0 + (1.0 × Spectralis global value). Based on 228 controls, the equation for GCIPL was Cirrus = -4.5 + (0.9 × Spectralis global value). Standard error was 0.02 for both equations. After the age of 40 years, there was a decline of -2.4 µm per decade in pRNFL thickness ( P < 0.001, GEE models adjusting for sex, race, and country) and -1.4 µm per decade in GCIPL thickness ( P < 0.001). There was a small difference in pRNFL thickness based on sex, with female participants having slightly higher thickness (2.6 µm, P = 0.003). There was no association between GCIPL thickness and sex. Likewise, there was no association between race/ethnicity and pRNFL or GCIPL thicknesses. CONCLUSIONS: A conversion factor may be required when using data that are derived between different SD-OCT platforms in clinical trials and observational studies; this is particularly true for smaller cross-sectional studies or when a consistent segmentation algorithm is not available. The above conversion equations can be used when pooling data from Spectralis and Cirrus SD-OCT devices for pRNFL and GCIPL thicknesses. A faster decline in retinal thickness may occur after the age of 40 years, even in the absence of significant differences across racial groups.
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Esclerose Múltipla , Tomografia de Coerência Óptica , Masculino , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Tomografia de Coerência Óptica/métodos , Fibras Nervosas , Células Ganglionares da Retina , Estudos Transversais , Esclerose Múltipla/diagnóstico por imagemRESUMO
Intracranial pressure (ICP) has been proposed to play an important role in the sensitivity to intraocular pressure (IOP) and susceptibility to glaucoma. However, the in vivo effects of simultaneous, controlled, acute variations in ICP and IOP have not been directly measured. We quantified the deformations of the anterior lamina cribrosa (ALC) and scleral canal at Bruch's membrane opening (BMO) under acute elevation of IOP and/or ICP. Four eyes of three adult monkeys were imaged in vivo with OCT under four pressure conditions: IOP and ICP either at baseline or elevated. The BMO and ALC were reconstructed from manual delineations. From these, we determined canal area at the BMO (BMO area), BMO aspect ratio and planarity, and ALC median depth relative to the BMO plane. To better account for the pressure effects on the imaging, we also measured ALC visibility as a percent of the BMO area. Further, ALC depths were analyzed only in regions where the ALC was visible in all pressure conditions. Bootstrap sampling was used to obtain mean estimates and confidence intervals, which were then used to test for significant effects of IOP and ICP, independently and in interaction. Response to pressure manipulation was highly individualized between eyes, with significant changes detected in a majority of the parameters. Significant interactions between ICP and IOP occurred in all measures, except ALC visibility. On average, ICP elevation expanded BMO area by 0.17 mm2 at baseline IOP, and contracted BMO area by 0.02 mm2 at high IOP. ICP elevation decreased ALC depth by 10 µm at baseline IOP, but increased depth by 7 µm at high IOP. ALC visibility decreased as ICP increased, both at baseline (-10%) and high IOP (-17%). IOP elevation expanded BMO area by 0.04 mm2 at baseline ICP, and contracted BMO area by 0.09 mm2 at high ICP. On average, IOP elevation caused the ALC to displace 3.3 µm anteriorly at baseline ICP, and 22 µm posteriorly at high ICP. ALC visibility improved as IOP increased, both at baseline (5%) and high ICP (8%). In summary, changing IOP or ICP significantly deformed both the scleral canal and the lamina of the monkey ONH, regardless of the other pressure level. There were significant interactions between the effects of IOP and those of ICP on LC depth, BMO area, aspect ratio and planarity. On most eyes, elevating both pressures by the same amount did not cancel out the effects. Altogether our results show that ICP affects sensitivity to IOP, and thus that it can potentially also affect susceptibility to glaucoma.
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Hipertensão Intracraniana/fisiopatologia , Pressão Intracraniana/fisiologia , Pressão Intraocular/fisiologia , Hipertensão Ocular/fisiopatologia , Disco Óptico/fisiopatologia , Animais , Pressão Sanguínea/fisiologia , Lâmina Basilar da Corioide/fisiopatologia , Modelos Animais de Doenças , Frequência Cardíaca/fisiologia , Imageamento Tridimensional , Hipertensão Intracraniana/diagnóstico por imagem , Macaca mulatta , Hipertensão Ocular/diagnóstico por imagem , Disco Óptico/diagnóstico por imagem , Esclera/fisiopatologia , Tomografia de Coerência Óptica , Tonometria OcularRESUMO
PURPOSE: To determine which spectral domain optical coherence tomography biomarkers of idiopathic macular hole (MH) correlate with the postoperative best-corrected visual acuity (BCVA) in anatomically closed MH. METHODS: Retrospective analysis of spectral domain optical coherence tomography scans of 44 patients presenting with MH followed for a mean of 17 months. Widths of MH aperture, base, and ellipsoid zone disruption were calculated from presenting foveal spectral domain optical coherence tomography B-scans. Macular hole base area and ellipsoid zone disruption area were calculated through the custom in-house software. RESULTS: Poorer postoperative BCVA correlated with increased preoperative choroidal hypertransmission (r = 0.503, P = 0.0005), minimum diameter (r = 0.491, P = 0.0007), and base diameter (r = 0.319, P = 0.0348), but not with preoperative ellipsoid zone width (r = 0.199, P = 0.2001). Applying en-face analysis, the BCVA correlated weakly with preoperative ellipsoid zone loss area (r = 0.380, P = 0.013), but not with preoperative MH base area (r = 0.253, P = 0.1058). CONCLUSION: Increased MH minimum diameter, base diameter, base area, and choroidal hypertransmission are correlated with a poorer postoperative BCVA. Ellipsoid zone loss measurements were not consistently correlated with a BCVA. Choroidal hypertransmission width may be an easy-to-visualize predictive imaging biomarker in MH surgery.
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Fóvea Central/patologia , Perfurações Retinianas/cirurgia , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Vitrectomia/métodos , Idoso , Feminino , Humanos , Masculino , Período Pós-Operatório , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/fisiopatologia , Estudos RetrospectivosRESUMO
PURPOSE: To evaluate the ability of OCT optic nerve head (ONH) and macular parameters to detect disease progression in eyes with advanced structural glaucomatous damage of the circumpapillary retinal nerve fiber layer (cRNFL). DESIGN: Longitudinal study. PARTICIPANTS: Forty-four eyes from 37 patients with advanced average cRNFL damage (≤60 µm) followed up for an average of 4.0 years. METHODS: All patients were examined with spectral-domain OCT and visual field (VF) assessment during at least 4 visits. MAIN OUTCOME MEASUREMENTS: Visual field mean deviation (MD) and VF index. OCT cRNFL (average, superior, and inferior quadrants), ganglion cell-inner plexiform layer (GCIPL) (average, superior, and inferior), rim area, cup volume, average cup-to-disc (C:D) ratio, and vertical C:D ratio. RESULTS: At baseline, patients had a median VF MD of -10.18 dB and mean cRNFL of 54.55±3.42 µm. The rate of change for MD and VF index were significant. No significant rate of change was noted for cRNFL, whereas significant (P < 0.001) rates were detected for GCIPL (-0.57±0.05 µm/year) and ONH parameters such as rim area (-0.010±0.001 mm2/year). CONCLUSIONS: Macula GCIPL and ONH parameters may be useful in tracking progression in patients with advanced glaucoma.
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Glaucoma de Ângulo Aberto/diagnóstico , Macula Lutea/patologia , Fibras Nervosas/patologia , Disco Óptico/patologia , Doenças do Nervo Óptico/diagnóstico , Células Ganglionares da Retina/patologia , Idoso , Progressão da Doença , Feminino , Seguimentos , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Pressão Intraocular/fisiologia , Macula Lutea/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Disco Óptico/diagnóstico por imagem , Doenças do Nervo Óptico/fisiopatologia , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Testes de Campo Visual , Campos Visuais/fisiologiaRESUMO
PURPOSE: Previously, we introduced a state-based 2-dimensional continuous-time hidden Markov model (2D CT HMM) to model the pattern of detected glaucoma changes using structural and functional information simultaneously. The purpose of this study was to evaluate the detected glaucoma change prediction performance of the model in a real clinical setting using a retrospective longitudinal dataset. DESIGN: Longitudinal, retrospective study. PARTICIPANTS: One hundred thirty-four eyes from 134 participants diagnosed with glaucoma or as glaucoma suspects (average follow-up, 4.4±1.2 years; average number of visits, 7.1±1.8). METHODS: A 2D CT HMM model was trained using OCT (Cirrus HD-OCT; Zeiss, Dublin, CA) average circumpapillary retinal nerve fiber layer (cRNFL) thickness and visual field index (VFI) or mean deviation (MD; Humphrey Field Analyzer; Zeiss). The model was trained using a subset of the data (107 of 134 eyes [80%]) including all visits except for the last visit, which was used to test the prediction performance (training set). Additionally, the remaining 27 eyes were used for secondary performance testing as an independent group (validation set). The 2D CT HMM predicts 1 of 4 possible detected state changes based on 1 input state. MAIN OUTCOME MEASURES: Prediction accuracy was assessed as the percentage of correct prediction against the patient's actual recorded state. In addition, deviations of the predicted long-term detected change paths from the actual detected change paths were measured. RESULTS: Baseline mean ± standard deviation age was 61.9±11.4 years, VFI was 90.7±17.4, MD was -3.50±6.04 dB, and cRNFL thickness was 74.9±12.2 µm. The accuracy of detected glaucoma change prediction using the training set was comparable with the validation set (57.0% and 68.0%, respectively). Prediction deviation from the actual detected change path showed stability throughout patient follow-up. CONCLUSIONS: The 2D CT HMM demonstrated promising prediction performance in detecting glaucoma change performance in a simulated clinical setting using an independent cohort. The 2D CT HMM allows information from just 1 visit to predict at least 5 subsequent visits with similar performance.
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Glaucoma/diagnóstico , Pressão Intraocular/fisiologia , Disco Óptico/patologia , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Campos Visuais/fisiologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Valor Preditivo dos Testes , Estudos Prospectivos , Estudos Retrospectivos , Fatores de TempoRESUMO
Ocular imaging has been heavily incorporated into glaucoma management and provides important information that aids in the detection of disease progression. Longitudinal studies have shown that the circumpapillary retinal nerve fiber layer is an important parameter for glaucoma progression detection, whereas other studies have demonstrated that macular parameters, such as the ganglion cell inner plexiform layer and optic nerve head parameters, also are useful for progression detection. The introduction of novel technologies with faster scan speeds, wider scanning fields, higher resolution, and improved tissue penetration has enabled the precise quantification of additional key ocular structures, such as the individual retinal layers, optic nerve head, choroid, and lamina cribrosa. Furthermore, extracting functional information from scans such as blood flow rate and oxygen consumption provides new perspectives on the disease and its progression. These novel methods promise improved detection of glaucoma progression and better insight into the mechanisms of progression that will lead to better targeted treatment options to prevent visual damage and blindness.
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Diagnóstico por Imagem/tendências , Técnicas de Diagnóstico Oftalmológico/tendências , Glaucoma de Ângulo Aberto/diagnóstico , Doenças do Nervo Óptico/diagnóstico , Progressão da Doença , Humanos , Fibras Nervosas/patologia , Células Ganglionares da Retina/patologiaRESUMO
PURPOSE: To compare the rate of glaucoma structural and functional progression in American and Korean cohorts. DESIGN: Retrospective longitudinal study. PARTICIPANTS: Three hundred thirteen eyes from 189 glaucoma and glaucoma suspects, followed up for an average of 38 months. METHODS: All subjects were examined semiannually with visual field (VF) testing and spectral-domain optical coherence tomography. All subjects had 5 or more reliable visits. MAIN OUTCOME MEASUREMENTS: The rates of change of retinal nerve fiber layer (RNFL) thickness, cup-to-disc (C/D) ratios, and VF mean deviation (MD) were compared between the cohorts. Variables affecting the rate of change for each parameter were determined, including ethnicity, refraction, baseline age and disease severity, disease subtype (high- vs. normal-tension glaucoma), clinical diagnosis (glaucoma vs. glaucoma suspect), and the interactions between variables. RESULTS: The Korean cohort predominantly demonstrated normal-tension glaucoma, whereas the American cohort predominantly demonstrated high-tension glaucoma. Cohorts had similar VF parameters at baseline, but the Korean eyes had significantly thicker mean RNFL and larger cups. Korean glaucoma eyes showed a faster thinning of mean RNFL (mean, -0.71 µm/year vs. -0.24 µm/year; P < 0.01). There were no detectable differences in the rate of change between the glaucoma cohorts for C/D ratios and VF MD and for all parameters in glaucoma suspect eyes. Different combinations of the tested variables significantly impacted the rate of change. CONCLUSIONS: Ethnicity, baseline disease severity, disease subtype, and clinical diagnosis should be considered when comparing glaucoma progression studies.
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Glaucoma/diagnóstico , Pressão Intraocular/fisiologia , Fibras Nervosas/patologia , Disco Óptico/patologia , Doenças do Nervo Óptico/diagnóstico , Células Ganglionares da Retina/patologia , Idoso , Progressão da Doença , Etnicidade , Feminino , Seguimentos , Glaucoma/classificação , Glaucoma/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/diagnóstico , Hipertensão Ocular/etnologia , Doenças do Nervo Óptico/etnologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Estados Unidos/epidemiologia , Testes de Campo Visual , Campos VisuaisRESUMO
PURPOSE OF REVIEW: Optical coherence tomography (OCT) has become the cornerstone technology for clinical ocular imaging in the past few years. The technology is still rapidly evolving with newly developed applications. This manuscript reviews recent innovative OCT applications for glaucoma diagnosis and management. RECENT FINDINGS: The improvements made in the technology have resulted in increased scanning speed, axial and transverse resolution, and more effective use of the OCT technology as a component of multimodal imaging tools. At the same time, the parallel evolution in novel algorithms makes it possible to efficiently analyze the increased volume of acquired data. SUMMARY: The innovative iterations of OCT technology have the potential to further improve the performance of the technology in evaluating ocular structural and functional characteristics and longitudinal changes in glaucoma.
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Técnicas de Diagnóstico Oftalmológico , Tomografia de Coerência Óptica/métodos , Anatomia Transversal , Glaucoma/diagnóstico , HumanosRESUMO
Optic nerve degeneration caused by glaucoma is a leading cause of blindness worldwide. Patients affected by the normal-pressure form of glaucoma are more likely to harbor risk alleles for glaucoma-related optic nerve disease. We have performed a meta-analysis of two independent genome-wide association studies for primary open angle glaucoma (POAG) followed by a normal-pressure glaucoma (NPG, defined by intraocular pressure (IOP) less than 22 mmHg) subgroup analysis. The single-nucleotide polymorphisms that showed the most significant associations were tested for association with a second form of glaucoma, exfoliation-syndrome glaucoma. The overall meta-analysis of the GLAUGEN and NEIGHBOR dataset results (3,146 cases and 3,487 controls) identified significant associations between two loci and POAG: the CDKN2BAS region on 9p21 (rs2157719 [G], ORâ=â0.69 [95%CI 0.63-0.75], pâ=â1.86×10⻹8), and the SIX1/SIX6 region on chromosome 14q23 (rs10483727 [A], ORâ=â1.32 [95%CI 1.21-1.43], pâ=â3.87×10⻹¹). In sub-group analysis two loci were significantly associated with NPG: 9p21 containing the CDKN2BAS gene (rs2157719 [G], ORâ=â0.58 [95% CI 0.50-0.67], pâ=â1.17×10⻹²) and a probable regulatory region on 8q22 (rs284489 [G], ORâ=â0.62 [95% CI 0.53-0.72], pâ=â8.88×10⻹°). Both NPG loci were also nominally associated with a second type of glaucoma, exfoliation syndrome glaucoma (rs2157719 [G], ORâ=â0.59 [95% CI 0.41-0.87], pâ=â0.004 and rs284489 [G], ORâ=â0.76 [95% CI 0.54-1.06], pâ=â0.021), suggesting that these loci might contribute more generally to optic nerve degeneration in glaucoma. Because both loci influence transforming growth factor beta (TGF-beta) signaling, we performed a genomic pathway analysis that showed an association between the TGF-beta pathway and NPG (permuted pâ=â0.009). These results suggest that neuro-protective therapies targeting TGF-beta signaling could be effective for multiple forms of glaucoma.
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Síndrome de Exfoliação/genética , Estudo de Associação Genômica Ampla , Glaucoma de Ângulo Aberto/genética , Degeneração Neural , Fator de Crescimento Transformador beta , Alelos , Cromossomos Humanos Par 8 , Cromossomos Humanos Par 9 , Proteínas de Homeodomínio/genética , Humanos , Degeneração Neural/genética , Degeneração Neural/patologia , Nervo Óptico/patologia , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante , RNA não Traduzido/genética , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismoRESUMO
Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. Using genome-wide association single-nucleotide polymorphism data from the Glaucoma Genes and Environment study and National Eye Institute Glaucoma Human Genetics Collaboration comprising 3,108 cases and 3,430 controls, we assessed biologic pathways as annotated in the KEGG database for association with risk of POAG. After correction for genic overlap among pathways, we found 4 pathways, butanoate metabolism (hsa00650), hematopoietic cell lineage (hsa04640), lysine degradation (hsa00310) and basal transcription factors (hsa03022) related to POAG with permuted p < 0.001. In addition, the human leukocyte antigen (HLA) gene family was significantly associated with POAG (p < 0.001). In the POAG subset with normal-pressure glaucoma (NPG), the butanoate metabolism pathway was also significantly associated (p < 0.001) as well as the MAPK and Hedgehog signaling pathways (hsa04010 and hsa04340), glycosaminoglycan biosynthesis-heparan sulfate pathway (hsa00534) and the phenylalanine, tyrosine and tryptophan biosynthesis pathway (hsa0400). The butanoate metabolism pathway overall, and specifically the aspects of the pathway that contribute to GABA and acetyl-CoA metabolism, was the only pathway significantly associated with both POAG and NPG. Collectively these results implicate GABA and acetyl-CoA metabolism in glaucoma pathogenesis, and suggest new potential therapeutic targets.
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Acetilcoenzima A/metabolismo , Glaucoma de Ângulo Aberto/genética , Glaucoma/genética , Redes e Vias Metabólicas/genética , Ácido gama-Aminobutírico/metabolismo , Estudos de Casos e Controles , Análise por Conglomerados , Feminino , Predisposição Genética para Doença , Glaucoma/metabolismo , Glaucoma de Ângulo Aberto/metabolismo , Humanos , Pressão Intraocular/genética , Masculino , Modelos Genéticos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
PURPOSE: The CAV1/CAV2 (caveolin 1 and caveolin 2) genomic region previously was associated with primary open-angle glaucoma (POAG), although replication among independent studies has been variable. The aim of this study was to assess the association between CAV1/CAV2 single nucleotide polymorphisms (SNPs) and POAG in a large case-control dataset and to explore associations by gender and pattern of visual field (VF) loss further. DESIGN: Case-control study. PARTICIPANTS: We analyzed 2 large POAG data sets: the Glaucoma Genes and Environment (GLAUGEN) study (976 cases, 1140 controls) and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium (2132 cases, 2290 controls). METHODS: We studied the association between 70 SNPs located within the CAV1/CAV2 genomic region in the GLAUGEN and NEIGHBOR studies, both genotyped on the Illumina Human 660WQuadv1C BeadChip array and imputed with the Markov Chain Haplotyping algorithm using the HapMap 3 reference panel. We used logistic regression models of POAG in the overall population and separated by gender, as well as by POAG subtypes defined by type of VF defect (peripheral or paracentral). Results from GLAUGEN and NEIGHBOR were meta-analyzed, and a Bonferroni-corrected significance level of 7.7 × 10(-4) was used to account for multiple comparisons. MAIN OUTCOME MEASURES: Overall POAG, overall POAG by gender, and POAG subtypes defined by pattern of early VF loss. RESULTS: We found significant associations between 10 CAV1/CAV2 SNPs and POAG (top SNP, rs4236601; pooled P = 2.61 × 10(-7)). Of these, 9 were significant only in women (top SNP, rs4236601; pooled P = 1.59 × 10(-5)). Five of the 10 CAV1/CAV2 SNPs were associated with POAG with early paracentral VF (top SNP, rs17588172; pooled P = 1.07 × 10(-4)), and none of the 10 were associated with POAG with peripheral VF loss only or POAG among men. CONCLUSIONS: CAV1/CAV2 SNPs were associated significantly with POAG overall, particularly among women. Furthermore, we found an association between CAV1/CAV2 SNPs and POAG with paracentral VF defects. These data support a role for caveolin 1, caveolin 2, or both in POAG and suggest that the caveolins particularly may affect POAG pathogenesis in women and in patients with early paracentral VF defects.
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Caveolina 1/genética , Caveolina 2/genética , Variação Estrutural do Genoma , Glaucoma de Ângulo Aberto/genética , Polimorfismo de Nucleotídeo Único , Transtornos da Visão/genética , Campos Visuais , Idoso , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Fatores SexuaisRESUMO
Purpose: To establish generalizable pointwise spatial relationship between structure and function through occlusion analysis of a deep-learning (DL) model for predicting the visual field (VF) sensitivities from 3-dimensional (3D) OCT scan. Design: Retrospective cross-sectional study. Participants: A total of 2151 eyes from 1129 patients. Methods: A DL model was trained to predict 52 VF sensitivities of 24-2 standard automated perimetry from 3D spectral-domain OCT images of the optic nerve head (ONH) with 12 915 OCT-VF pairs. Using occlusion analysis, the contribution of each individual cube covering a 240 × 240 × 31.25 µm region of the ONH to the model's prediction was systematically evaluated for each OCT-VF pair in a separate test set that consisted of 996 OCT-VF pairs. After simple translation (shifting in x- and y-axes to match the ONH center), group t-statistic maps were derived to visualize statistically significant ONH regions for each VF test point within a group. This analysis allowed for understanding the importance of each super voxel (240 × 240 × 31.25 µm covering the entire 4.32 × 4.32 × 1.125 mm ONH cube) in predicting VF test points for specific patient groups. Main Outcome Measures: The region at the ONH corresponding to each VF test point and the effect of the former on the latter. Results: The test set was divided to 2 groups, the healthy-to-early-glaucoma group (792 OCT-VF pairs, VF mean deviation [MD]: -1.32 ± 1.90 decibels [dB]) and the moderate-to-advanced-glaucoma group (204 OCT-VF pairs, VF MD: -17.93 ± 7.68 dB). Two-dimensional group t-statistic maps (x, y projection) were generated for both groups, assigning related ONH regions to visual field test points. The identified influential structural locations for VF sensitivity prediction at each test point aligned well with existing knowledge and understanding of structure-function spatial relationships. Conclusions: This study successfully visualized the global trend of point-by-point spatial relationships between OCT-based structure and VF-based function without the need for prior knowledge or segmentation of OCTs. The revealed spatial correlations were consistent with previously published mappings. This presents possibilities of learning from trained machine learning models without applying any prior knowledge, potentially robust, and free from bias. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Purpose: Broken stick analysis is a widely used approach for detecting unknown breakpoints where the association between measurements is nonlinear. We propose LIMBARE, an advanced linear mixed-effects breakpoint analysis with robust estimation, especially designed for longitudinal ophthalmic studies. LIMBARE accommodates repeated measurements from both eyes and over time, and it effectively addresses the presence of outliers. Methods: The model setup of LIMBARE and the computing algorithm for point and confidence interval estimates of the breakpoint were introduced. The performance of LIMBARE and other competing methods was assessed via comprehensive simulation studies and application to a longitudinal ophthalmic study with 216 eyes (145 subjects) followed for an average of 3.7 ± 1.3 years to examine the longitudinal association between structural and functional measurements. Results: In simulation studies, LIMBARE showed the smallest bias and mean squared error for estimating the breakpoint, with an empirical coverage probability of corresponding confidence interval estimates closest to the nominal level for scenarios with and without outlier data points. In the application to the longitudinal ophthalmic study, LIMBARE detected two breakpoints between visual field mean deviation (MD) and retinal nerve fiber layer thickness and one breakpoint between MD and cup-to-disc ratio, whereas the cross-sectional analysis approach detected only one and none, respectively. Conclusions: LIMBARE enhances breakpoint estimation accuracy in longitudinal ophthalmic studies, and the cross-sectional analysis approach is not recommended for future studies. Translational Relevance: Our proposed method and companion R package provide a valuable computational tool for advancing longitudinal ophthalmology research and exploring the association relationships among ophthalmic variables.
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Retina , Tomografia de Coerência Óptica , Humanos , Estudos Transversais , Tomografia de Coerência Óptica/métodos , Campos Visuais , Fibras NervosasRESUMO
Purpose: To investigate the contributions of the microstructural and metabolic brain environment to glaucoma and their association with visual field (VF) loss patterns by using advanced diffusion magnetic resonance imaging (dMRI), proton magnetic resonance spectroscopy (MRS), and clinical ophthalmic measures. Methods: Sixty-nine glaucoma and healthy subjects underwent dMRI and/or MRS at 3 Tesla. Ophthalmic data were collected from VF perimetry and optical coherence tomography. dMRI parameters of microstructural integrity in the optic radiation and MRS-derived neurochemical levels in the visual cortex were compared among early glaucoma, advanced glaucoma, and healthy controls. Multivariate regression was used to correlate neuroimaging metrics with 16 archetypal VF loss patterns. We also ranked neuroimaging, ophthalmic, and demographic attributes in terms of their information gain to determine their importance to glaucoma. Results: In dMRI, decreasing fractional anisotropy, radial kurtosis, and tortuosity and increasing radial diffusivity correlated with greater overall VF loss bilaterally. Regionally, decreasing intra-axonal space and extra-axonal space diffusivities correlated with greater VF loss in the superior-altitudinal area of the right eye and the inferior-altitudinal area of the left eye. In MRS, both early and advanced glaucoma patients had lower gamma-aminobutyric acid (GABA), glutamate, and choline levels than healthy controls. GABA appeared to associate more with superonasal VF loss, and glutamate and choline more with inferior VF loss. Choline ranked third for importance to early glaucoma, whereas radial kurtosis and GABA ranked fourth and fifth for advanced glaucoma. Conclusions: Our findings highlight the importance of non-invasive neuroimaging biomarkers and analytical modeling for unveiling glaucomatous neurodegeneration and how they reflect complementary VF loss patterns.
Assuntos
Tomografia de Coerência Óptica , Testes de Campo Visual , Campos Visuais , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Campos Visuais/fisiologia , Tomografia de Coerência Óptica/métodos , Idoso , Transtornos da Visão/fisiopatologia , Transtornos da Visão/metabolismo , Imagem de Difusão por Ressonância Magnética , Glaucoma/fisiopatologia , Glaucoma/metabolismo , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Glaucoma de Ângulo Aberto/metabolismo , Glaucoma de Ângulo Aberto/fisiopatologia , Córtex Visual/metabolismo , Córtex Visual/diagnóstico por imagem , Espectroscopia de Prótons por Ressonância Magnética , Adulto , Pressão Intraocular/fisiologiaRESUMO
Purpose: This study aims to investigate the prevalence of artifacts in optical coherence tomography (OCT) images with acceptable signal strength and evaluate the performance of supervised deep learning models in improving OCT image quality assessment. Methods: We conducted a retrospective study on 4555 OCT images from 546 patients, with each image having an acceptable signal strength (≥6). A comprehensive analysis of prevalent OCT artifacts was performed, and five pretrained convolutional neural network models were trained and tested to infer images based on quality. Results: Our results showed a high prevalence of artifacts in OCT images with acceptable signal strength. Approximately 21% of images were labeled as nonacceptable quality. The EfficientNetV2 model demonstrated superior performance in classifying OCT image quality, achieving an area under the receiver operating characteristic curve of 0.950 ± 0.007 and an area under the precision recall curve of 0.985 ± 0.002. Conclusions: The findings highlight the limitations of relying solely on signal strength for OCT image quality assessment and the potential of deep learning models in accurately classifying image quality. Translational Relevance: Application of the deep learning-based OCT image quality assessment models may improve the OCT image data quality for both clinical applications and research.
Assuntos
Artefatos , Aprendizado Profundo , Tomografia de Coerência Óptica , Tomografia de Coerência Óptica/métodos , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Curva ROC , Prevalência , Redes Neurais de Computação , Idoso , AdultoRESUMO
The cellular-level visualization of retinal microstructures such as blood vessel wall components, not available with other imaging modalities, is provided with unprecedented details by dark-field imaging configurations; however, the interpretation of such images alone is sometimes difficult since multiple structural disturbances may be present in the same time. Particularly in eyes with retinal pathology, microstructures may appear in high-resolution retinal images with a wide range of sizes, sharpnesses, and brightnesses. In this paper we show that motion contrast and phase gradient imaging modalities, as well as the simultaneous acquisition of depth-resolved optical coherence tomography (OCT) images, provide additional insight to help understand the retinal neural and vascular structures seen in dark-field images and may enable improved diagnostic and treatment plans.
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Purpose: To determine whether peripapillary atrophy (PPA) area is an indicator of glaucomatous structural and functional damage and progression. Methods: In this retrospective longitudinal analysis from ongoing prospective study we qualified 71 eyes (50 subjects) with glaucoma. All subjects had a comprehensive ophthalmic examination, visual field (VF), and spectral-domain optical coherence tomography (OCT) testing in at least three visits. PPA was manually delineated on en face OCT optic nerve head scans, while observing the corresponding cross-sectional images, as the hyper-reflective area contiguous with the optic disc. Results: The mean follow-up duration was 4.4 ± 1.4 years with an average of 6.8 ± 2.2 visits. At baseline, PPA area was significantly associated only with VF's mean deviation (MD; P = 0.041), visual field index (VFI; P = 0.041), superior ganglion cell inner plexiform layer (GCIPL; P = 0.011), and disc area (P = 0.011). Longitudinally, PPA area was negatively and significantly associated with MD (P = 0.015), VFI (P = 0.035), GCIPL (P = 0.009), superior GCIPL (P = 0.034), and disc area (P = 0.007, positive association). Conclusions: Longitudinal change in PPA area is an indicator of glaucomatous structural and functional progression but PPA area at baseline cannot predict future progression. Translational Relevance: Longitudinal changes in peripapillary atrophy area measured by OCT can be an indicator of structural and functional glaucoma progression.
Assuntos
Glaucoma , Pressão Intraocular , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Progressão da Doença , Células Ganglionares da Retina/patologia , Glaucoma/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Atrofia/patologiaRESUMO
Purpose: Prior evidence suggests racial disparities in the utilization of visual field testing (VFT) for the diagnosis and monitoring of glaucoma. In this study, we considered the effect of baseline glaucoma severity and socioeconomic disadvantage along with other potential confounders such as test reliability, ancillary tests, and glaucoma surgeries on racial disparity in the frequency of VFT. Methods: The records of all subjects with a diagnosis of glaucoma who received VFT at an academic, tertiary care facility from January 2018 to December 2021 were accessed. Analysis was performed to compare VFT frequency, the total number of office visits (DoS), and the ratio of VFT frequency to DoS (VFT/DoS) across self-reported races while controlling for sex, age, socioeconomic disadvantage (Area Deprivation Index), VF reliability indicators and baseline mean deviation, optical coherence tomography frequency, and glaucoma surgeries. Results: Among the 2654 subjects (1515 White, 782 Black, and 357 Asian) included in this study, Black subjects had the worst socioeconomic status and disease severity at baseline. They also experienced a 3% lower VFT/DoS ratio compared to White subjects (P = 0.031). Asian subjects had a 5% lower VFT/DoS ratio compared to White subjects (P = 0.015). Discussion: We identified racial disparity in performing VFT in subjects with glaucoma even when multiple confounders were considered. Further investigation is necessary to identify other race-associated factors to work toward reducing racial disparities in VFT. Translational Relevance: Black and Asian subjects with glaucoma receive fewer VFT per visit compared to White subjects even when considering socioeconomic disadvantage and disease severity.
Assuntos
Glaucoma , Campos Visuais , Humanos , Asiático , Glaucoma/diagnóstico , Reprodutibilidade dos Testes , Tomografia de Coerência Óptica , Brancos , Negro ou Afro-AmericanoRESUMO
Excitotoxicity from the impairment of glutamate uptake constitutes an important mechanism in neurodegenerative diseases such as Alzheimer's, multiple sclerosis, and Parkinson's disease. Within the eye, excitotoxicity is thought to play a critical role in retinal ganglion cell death in glaucoma, diabetic retinopathy, retinal ischemia, and optic nerve injury, yet how excitotoxic injury impacts different retinal layers is not well understood. Here, we investigated the longitudinal effects of N-methyl-D-aspartate (NMDA)-induced excitotoxic retinal injury in a rat model using deep learning-assisted retinal layer thickness estimation. Before and after unilateral intravitreal NMDA injection in nine adult Long Evans rats, spectral-domain optical coherence tomography (OCT) was used to acquire volumetric retinal images in both eyes over 4 weeks. Ten retinal layers were automatically segmented from the OCT data using our deep learning-based algorithm. Retinal degeneration was evaluated using layer-specific retinal thickness changes at each time point (before, and at 3, 7, and 28 days after NMDA injection). Within the inner retina, our OCT results showed that retinal thinning occurred first in the inner plexiform layer at 3 days after NMDA injection, followed by the inner nuclear layer at 7 days post-injury. In contrast, the retinal nerve fiber layer exhibited an initial thickening 3 days after NMDA injection, followed by normalization and thinning up to 4 weeks post-injury. Our results demonstrated the pathological cascades of NMDA-induced neurotoxicity across different layers of the retina. The early inner plexiform layer thinning suggests early dendritic shrinkage, whereas the initial retinal nerve fiber layer thickening before subsequent normalization and thinning indicates early inflammation before axonal loss and cell death. These findings implicate the inner plexiform layer as an early imaging biomarker of excitotoxic retinal degeneration, whereas caution is warranted when interpreting the ganglion cell complex combining retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer thicknesses in conventional OCT measures. Deep learning-assisted retinal layer segmentation and longitudinal OCT monitoring can help evaluate the different phases of retinal layer damage upon excitotoxicity.