RESUMO
PURPOSE: To apply retinal nerve fiber layer (RNFL) optical texture analysis (ROTA) to investigate the prevalence, patterns, and risk factors of RNFL defects in patients with ocular hypertension (OHT) who showed normal optic disc and RNFL configuration in clinical examination, normal RNFL thickness on OCT analysis, and normal visual field (VF) results. DESIGN: Cross-sectional study. PARTICIPANTS: Six hundred eyes of 306 patients with OHT. METHODS: All participants underwent clinical examination of the optic disc and RNFL, OCT RNFL imaging, and 24-2 standard automated perimetry. To detect RNFL defects, ROTA was applied. The risk score for glaucoma development was calculated according to the Ocular Hypertension Treatment Study and European Glaucoma Prevention Study (OHTS-EGPS) risk prediction model. Risk factors associated with RNFL defects were analyzed using multilevel logistic regression analysis. MAIN OUTCOME MEASURES: Prevalence of RNFL defects. RESULTS: The average intraocular pressure (IOP) measured from 3 separate visits within 6 months was 24.9 ± 1.8 mmHg for the eye with higher IOP and 23.7 ± 1.7 mmHg for the eye with lower IOP; the respective central corneal thicknesses were 568.7 ± 30.8 µm and 568.8 ± 31.2 µm. Of 306 patients with OHT, 10.8% (33 patients, 37 eyes) demonstrated RNFL defects in ROTA in at least 1 eye. Of the 37 eyes with RNFL defects, the superior arcuate bundle was the most frequently involved (62.2%), followed by the superior papillomacular bundle (27.0%) and the inferior papillomacular bundle (21.6%). Papillofoveal bundle defects were observed in 10.8% of eyes. The smallest RNFL defect spanned 0.0° along Bruch's membrane opening margin, whereas the widest RNFL defect extended over 29.3°. Age (years) (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.03-1.13), VF pattern standard deviation (decibels [dB]) (OR, 1.82; 95% CI, 1.01-3.29), cup volume (mm3) (OR, 1.24; 95% CI, 1.01-1.53), and the OHTS-EPGS risk score (OR, 1.04; 95% CI, 1.01-1.07) were associated with RNFL defects. CONCLUSIONS: A considerable proportion of patients with OHT who showed no signs of optic disc and RNFL thickness abnormalities on clinical and OCT examination exhibited RNFL defects on ROTA. Axonal fiber bundle defects on ROTA may represent the earliest discernible sign of glaucoma in the glaucoma continuum. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Assuntos
Glaucoma , Hipertensão Ocular , Humanos , Estudos Transversais , Células Ganglionares da Retina , Campos Visuais , Fibras Nervosas , Glaucoma/diagnóstico , Hipertensão Ocular/diagnóstico , Pressão Intraocular , Tomografia de Coerência Óptica/métodosRESUMO
PURPOSE: To investigate the extent of iris trabecular contact (ITC) measured by anterior segment OCT (AS-OCT) and its association with primary angle-closure (PAC) and PAC glaucoma (PACG) in eyes with gonioscopic angle-closure and to determine the diagnostic performance of ITC for detection of gonioscopic angle-closure. DESIGN: Multicenter, prospective study. PARTICIPANTS: A total of 119 healthy participants with gonioscopic open-angle and 170 patients with gonioscopic angle-closure (94 with PAC suspect and 76 with PAC/PACG) were included. METHODS: One eye of each subject was randomly selected for AS-OCT imaging. Angle-opening distance (AOD500) and trabecular iris space area (TISA500) were measured every 10° for 360°. Two criteria of ITC500 were examined: (1) AOD500 = 0 mm and (2) TISA500 = 0 mm2. The association between the extent of ITC500 and PAC/PACG in eyes with gonioscopic angle-closure was analyzed with logistic regression analysis. MAIN OUTCOME MEASURES: Sensitivity and specificity of ITC500 for detection of gonioscopic angle-closure; odds ratio (OR) of PAC/PACG. RESULTS: The sensitivity of ITC500 ≥ 10° for detection of gonioscopic angle-closure ranged from 82.4% (AOD500 = 0 mm) to 84.7% (TISA500 = 0 mm2), and the specificity was 85.7% (for both AOD500 = 0 mm and TISA500 = 0 mm2). The extent of ITC500 determined by AS-OCT, not cumulative gonioscopy score (i.e., the sum of the modified Shaffer grades over 4 quadrants), was associated with the odds of PAC/PACG in eyes with gonioscopic angle-closure; the odds of PAC/PACG increased by 5% for every 10° increase in ITC500 (OR, 1.051, 95% confidence interval [CI], 1.022-1.080 for AOD500 = 0 mm; OR, 1.049, 95% CI, 1.022-1.078 for TISA500 = 0 mm2). Axial length and anterior chamber depth were not associated with PAC/PACG in eyes with gonioscopic angle-closure (P ≥ 0.574). CONCLUSIONS: A greater extent of ITC measured by AS-OCT, not angle-closure determined by gonioscopy, was associated with a greater odds of PAC/PACG in eyes with gonioscopic angle-closure.
Assuntos
Segmento Anterior do Olho , Glaucoma de Ângulo Fechado , Humanos , Gonioscopia , Estudos Prospectivos , Pressão Intraocular , Tomografia de Coerência Óptica/métodos , Iris , Glaucoma de Ângulo Fechado/diagnósticoRESUMO
OBJECTIVE: Evaluation of glaucoma progression with OCT has been centered on the analysis of progressive retinal nerve fiber layer (RNFL) thinning over the parapapillary region and/or progressive ganglion cell inner plexiform layer (GCIPL) thinning over the macula. We investigated (1) whether combining the RNFL and GCIPL as a single layer (i.e., RNFL-GCIPL) for wide-field progression analysis outperforms wide-field progression analysis of the RNFL or the GCIPL, and (2) whether eyes with progressive RNFL-GCIPL thinning are at risk of visual field (VF) progression. DESIGN: Prospective, longitudinal study. PARTICIPANTS: A total of 440 eyes from 236 glaucoma patients; 98 eyes from 49 healthy individuals. METHODS: OCT RNFL/GCIPL/RNFL-GCIPL thickness and VF measurements were obtained at â¼4-month intervals for ≥3 years. Progressive changes of the RNFL/GCIPL/RNFL-GCIPL thicknesses were analyzed over a wide field (12×9 mm2) covering the parapapillary region and the macula with trend-based progression analysis (TPA) controlled at a false discovery rate of 5%. VF progression was determined by the Early Manifest Glaucoma Trial criteria. MAIN OUTCOME MEASURES: Proportions of eyes with progressive RNFL/GCIPL/RNFL-GCIPL thinning; hazard ratios (HRs) for development of VF progression. RESULTS: More eyes showed progressive RNFL-GCIPL thinning (127 eyes; 28.9%, 95% confidence interval [CI]: 23.9%-33.8%) than progressive RNFL thinning (74 eyes; 16.8%, 95% CI: 13.1%-20.6%) and progressive GCIPL thinning (26 eyes; 5.9%, 95% CI: 3.7%-8.1%) in the glaucoma group over the study follow-up. Progressive RNFL-GCIPL thinning was almost always detected before or simultaneously with progressive RNFL thinning or progressive GCIPL thinning. The specificity of TPA (estimated from the healthy group) for detection of progressive RNFL-GCIPL thinning, progressive RNFL thinning, and progressive GCIPL thinning was 83.7% (95% CI: 74.9%-92.4%), 94.9% (95% CI: 90.6%-99.2%), and 96.9% (95% CI: 93.5%-100.0%), respectively. Eyes with progressive RNFL-GCIPL thinning had a higher risk to develop possible (HR: 2.4, 95% CI: 1.2-5.0) or likely (HR: 4.6, 95% CI: 1.5-14.0) VF progression, with adjustment of covariates, compared with eyes without progressive RNFL-GCIPL thinning. CONCLUSIONS: Progression analysis of RNFL-GCIPL thickness reveals a significant portion of progressing eyes that neither progression analysis of RNFL thickness nor GCIPL thickness would identify. Wide-field progression analysis of RNFL-GCIPL thickness is effective to inform the risk of VF progression in glaucoma patients.
Assuntos
Glaucoma/diagnóstico , Pressão Intraocular/fisiologia , Macula Lutea/patologia , Disco Óptico/patologia , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Progressão da Doença , Feminino , Seguimentos , Glaucoma/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Nervosas , Estudos Prospectivos , Campos VisuaisRESUMO
Retinal ganglion cell (RGC) degeneration, leading to irreversible blindness in chronic optic neuropathies, commonly begins with dendritic shrinkage followed by axon degeneration. Although limited axon regeneration in the optic nerve is possible with a genetic deletion of PTEN/SOCS3 after optic nerve injury, the roles of PTEN/SOCS3 on dendritic preservation and regeneration remain unclear. This study investigated the effect of PTEN/SOCS3 genetic deletion on the structural integrity of RGC dendrites and axons in the retina following optic nerve crush. Using time-lapse, in vivo confocal scanning laser ophthalmoscopy to serially image dendritic and axonal arborizations of RGCs over six months after injury, RGC dendrites and axons were only preserved in Thy-1-YFP/PTEN-/- and Thy-1-YFP/PTEN-/-SOCS3-/- mice, and axons in the retina regenerated at a rate of 21.1 µm/day and 15.5 µm/day, respectively. By contrast, dendritic complexity significantly decreased in Thy-1-YFP-SOCS3-/- and control mice at a rate of 7.0 %/day and 7.1 %/day, respectively, and no axon regeneration in the retina was observed. RGC survival probability was higher in Thy-1-YFP/PTEN-/- and Thy-1-YFP/PTEN-/-SOCS3-/- mice compared with Thy-1-YFP-SOCS3-/- and control mice. The differential responses between the transgenic mice demonstrate that although a genetic deletion of PTEN, SOCS3, or PTEN/SOCS3 allows partial axon regeneration in the optic nerve after optic nerve crush, a deletion of PTEN, but not SOCS3, ameliorates RGC dendritic shrinkage. This shows that the signaling pathways involved in promoting axon regeneration do not equally contribute to the preservation of dendrites, which is crucial to the translational application of neuroregenerative therapies for visual restoration.
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Dendritos/fisiologia , Deleção de Genes , Fibras Nervosas/fisiologia , Traumatismos do Nervo Óptico/fisiopatologia , PTEN Fosfo-Hidrolase/genética , Células Ganglionares da Retina/fisiologia , Proteína 3 Supressora da Sinalização de Citocinas/genética , Animais , Dependovirus/genética , Feminino , Vetores Genéticos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Microscopia Confocal , Compressão Nervosa , Regeneração Nervosa/fisiologiaRESUMO
PURPOSE: Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide and mutations in known genes can only explain 5-6% of POAG. This study was conducted to identify novel POAG-causing genes and explore the pathogenesis of this disease. METHODS: Exome sequencing was performed in a Han Chinese cohort comprising 398 sporadic cases with POAG and 2010 controls, followed by replication studies by Sanger sequencing. A heterozygous Ramp2 knockout mouse model was generated for in vivo functional study. RESULTS: Using exome sequencing analysis and replication studies, we identified pathogenic variants in receptor activity-modifying protein 2 (RAMP2) within three genetically diverse populations (Han Chinese, German, and Indian). Six heterozygous RAMP2 pathogenic variants (Glu39Asp, Glu54Lys, Phe103Ser, Asn113Lysfs*10, Glu143Lys, and Ser171Arg) were identified among 16 of 4763 POAG patients, whereas no variants were detected in any exon of RAMP2 in 10,953 control individuals. Mutant RAMP2s aggregated in transfected cells and resulted in damage to the AM-RAMP2/CRLR-cAMP signaling pathway. Ablation of one Ramp2 allele led to cAMP reduction and retinal ganglion cell death in mice. CONCLUSION: This study demonstrated that disruption of RAMP2/CRLR-cAMP axis could cause POAG and identified a potential therapeutic intervention for POAG.
Assuntos
Glaucoma de Ângulo Aberto/genética , Proteína 2 Modificadora da Atividade de Receptores/genética , Animais , Povo Asiático , Células COS , Proteína Semelhante a Receptor de Calcitonina/genética , Proteína Semelhante a Receptor de Calcitonina/metabolismo , China , Chlorocebus aethiops , Estudos de Coortes , AMP Cíclico/genética , Predisposição Genética para Doença/genética , Glaucoma de Ângulo Aberto/metabolismo , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Mutação/genética , Linhagem , Polimorfismo de Nucleotídeo Único , Proteína 2 Modificadora da Atividade de Receptores/metabolismo , Sequenciamento do Exoma/métodosRESUMO
PURPOSE: To investigate the temporal relationship among progressive macular ganglion cell inner plexiform layer (GCIPL) thinning, progressive parapapillary retinal nerve fiber layer (RNFL) thinning, and visual field (VF) progression in patients with primary open-angle glaucoma (POAG). DESIGN: Prospective study. PARTICIPANTS: One hundred thirty-six POAG patients (231 eyes) followed up for ≥5 years. METHODS: OCT imaging of the macular GCIPL and parapapillary RNFL and perimetry were performed at â¼ 4-month intervals. Progressive GCIPL and RNFL thinning were determined by Guided Progression Analysis (GPA) of serial GCIPL and RNFL thickness maps. The specificities of GPA were calculated from the proportions of eyes with progressive GCIPL or RNFL thinning in 67 eyes of 36 healthy individuals followed up for ≥5 years. Visual field progression (likely or possible) was determined by the Early Manifest Glaucoma Trial criteria. MAIN OUTCOME MEASURES: Hazard ratios for VF progression, progressive RNFL thinning, and progressive GCIPL thinning, as determined by time-varying Cox models. RESULTS: GPA detected 57 eyes (24.7%) with progressive GCIPL thinning and 66 eyes (28.6%) with progressive RNFL thinning at a specificity of 95.5% and 91.0%, respectively. Thirty-five eyes (15.2%) demonstrated progressive RNFL and GCIPL thinning, whereas 53 eyes (22.9%) demonstrated progressive RNFL or GCIPL thinning. Eyes with progressive GCIPL thinning had a higher risk for progressive RNFL thinning (HR, 5.27; 95% confidence interval [CI], 2.89-9.62), whereas eyes with progressive RNFL thinning were also at a higher risk for progressive GCIPL thinning (HR, 2.99; 95% CI, 1.48-6.02), after adjusting for baseline covariates. The HRs for likely and possible VF progression were 3.48 (95% CI, 1.51-8.01) and 2.74 (95% CI, 1.26-5.98), respectively, on detection of progressive GCIPL thinning and 3.66 (95% CI, 1.68-7.97) and 2.54 (95% CI, 1.23-5.21), respectively, on detection of progressive RNFL thinning after adjusting for baseline covariates. Eyes with VF progression were not at risk of progressive RNFL or GCIPL thinning (P ≥ 0.493). CONCLUSIONS: Progressive macular GCIPL thinning and progressive parapapillary RNFL thinning are mutually predictive. Because progressive RNFL thinning and progressive GCIPL thinning are both indicative of VF progression, integrating macular GCIPL and parapapillary RNFL measurements is relevant to facilitate early detection of disease deterioration in glaucoma patients.
Assuntos
Glaucoma de Ângulo Aberto/diagnóstico , Fibras Nervosas/patologia , Disco Óptico/patologia , Doenças do Nervo Óptico/diagnóstico , Células Ganglionares da Retina/patologia , Progressão da Doença , Feminino , Seguimentos , Gonioscopia , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia de Coerência Óptica/métodos , Acuidade Visual/fisiologia , Testes de Campo Visual , Campos Visuais/fisiologiaRESUMO
PURPOSE: To investigate whether progressive retinal nerve fiber layer (RNFL) thinning is predictive of progressive visual field (VF) loss in glaucoma. DESIGN: Prospective study. PARTICIPANTS: A total of 139 primary open-angle glaucoma patients (240 eyes) followed up for ≥5 years. METHODS: Retinal nerve fiber layer imaging and VF testing were performed at â¼4-month intervals. Progressive RNFL thinning was determined by event analysis (Guided Progression Analysis [GPA]) and trend analysis (Trend-based Progression Analysis [TPA]) of serial registered RNFL thickness maps. VF progression was detected according to the Early Manifest Glaucoma Trial (EMGT) ("likely progression") and pointwise linear regression (PLR) criteria (≥3 contiguous locations with sensitivity change <0 decibels [dB]/year at P < 0.01). Hazard ratios (HRs) for predicting VF progression were calculated by Cox proportional hazard modeling with progressive RNFL thinning as a time-dependent covariate. The specificity of GPA/TPA for detection of RNFL changes was determined by the proportion of eyes with significant RNFL thinning/thickening in 25 normal subjects followed weekly for 8 consecutive weeks and the proportion with significant RNFL thickening in the glaucoma group. MAIN OUTCOME MEASURES: The HRs of VF progression. RESULTS: A total of 65 (27.1%) and 117 eyes (48.8%) had progressive RNFL thinning based on GPA and TPA, respectively, and 30 (12.5%) and 39 eyes (16.3%) had VF progression per the EMGT and PLR criteria, respectively, during follow-up. Eyes with progressive RNFL thinning had lower VF survival estimates and a faster decline of visual field index than eyes without. Progressive RNFL thinning predicted the development of VF progression with HRs of 8.44 (95% confidence interval, 3.30-21.61) (EMGT criteria) and 5.11 (2.51-10.42) (PLR criteria) for TPA and 3.95 (1.74-8.93) (EMGT criteria) and 3.81 (1.83-7.92) (PLR criteria) for GPA after controlling for baseline covariates. The specificities of GPA and TPA were 100% (83.4%-100.0%) in the normal group and 81.7% (76.2%-86.4%) and 84.2% (78.9%-88.6%), respectively, in the glaucoma group. CONCLUSIONS: Progressive RNFL thinning determined by GPA and TPA is predictive of detectable functional decline in glaucoma. This finding underscores the significance of detecting progressive RNFL thinning and its relevance to initiate or augment treatment for glaucoma patients. Regulatory authorities may consider progressive RNFL thinning as an outcome measure in clinical trials for evaluation of glaucoma treatment.
Assuntos
Glaucoma de Ângulo Aberto/diagnóstico , Fibras Nervosas/patologia , Doenças do Nervo Óptico/diagnóstico , Células Ganglionares da Retina/patologia , Transtornos da Visão/diagnóstico , Campos Visuais , Idoso , Progressão da Doença , Reações Falso-Positivas , Feminino , Seguimentos , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Disco Óptico/patologia , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Sensibilidade e Especificidade , Tomografia de Coerência Óptica/métodos , Tonometria Ocular , Testes de Campo VisualRESUMO
PURPOSE OF REVIEW: Optical coherence tomography (OCT) imaging of the retinal nerve fiber layer (RNFL), optic nerve head (ONH) and macula has gained popularity in recent years to detect and monitor glaucoma. With significant improvement in scan speed and scan resolution, spectral-domain OCT has become an efficient platform to evaluate progressive RNFL thinning and ONH remodeling. This review summarizes the recent progress of OCT RNFL, ONH and macular measurements for the detection of glaucoma progression. RECENT FINDINGS: The RNFL thickness map facilitates visualization of RNFL defects and their progression patterns, and attains a higher sensitivity to detect glaucoma progression compared with the conventional circumpapillary RNFL thickness profile. The measurement of lamina cribrosa displacement is informative to discern the relationship between intraocular pressure and ONH modeling. Ganglion cell and inner plexiform layer analysis has offered a useful alternative to track glaucoma progression. In the interpretation of progression analysis, the impact of age-related change, disease severity and image signal-to-noise ratio should always be considered. SUMMARY: The analyses of the RNFL thickness map, lamina cribrosa displacement and inner macular thickness have provided a new paradigm to evaluate glaucomatous damage and its progression.
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Glaucoma/diagnóstico , Disco Óptico/patologia , Doenças do Nervo Óptico/diagnóstico , Tomografia de Coerência Óptica/métodos , Progressão da Doença , Humanos , Fibras Nervosas/patologia , Células Ganglionares da Retina/patologiaRESUMO
AIMS: To compare the diagnostic performance of 360° anterior segment optical coherence tomography assessment by applying normative percentile cut-offs versus iris trabecular contact (ITC) for detecting gonioscopic angle closure. METHODS: In this multicentre study, 394 healthy individuals were included in the normative dataset to derive the age-specific and angle location-specific normative percentiles of angle open distance (AOD500) and trabecular iris space area (TISA500) which were measured every 10° for 360°. 119 healthy participants and 170 patients with angle closure by gonioscopy were included in the test dataset to investigate the diagnostic performance of three sets of criteria for detection of gonioscopic angle closure: (1) the 10th and (2) the 5th percentiles of AOD500/TISA500, and (3) ITC (ie, AOD500/TISA500=0 mm/mm2). The number of angle locations with angle closure defined by each set of the criteria for each eye was used to generate the receiver operating characteristic (ROC) curve for the discrimination between gonioscopic angle closure and open angle. RESULTS: Of the three sets of diagnostic criteria examined, the area under the ROC curve was greatest for the 10th percentile of AOD500 (0.933), whereas the ITC criterion AOD500=0 mm showed the smallest area under the ROC (0.852) and the difference was statistically significant with or without adjusting for age and axial length (p<0.001). The criterion ≥90° of AOD500 below the 10th percentile attained the best sensitivity 87.6% and specificity 84.9% combination for detecting gonioscopic angle closure. CONCLUSIONS: Applying the normative percentiles of angle measurements yielded a higher diagnostic performance than ITC for detecting angle closure on gonioscopy.
Assuntos
Segmento Anterior do Olho , Glaucoma de Ângulo Fechado , Gonioscopia , Pressão Intraocular , Curva ROC , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Glaucoma de Ângulo Fechado/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Segmento Anterior do Olho/diagnóstico por imagem , Segmento Anterior do Olho/patologia , Adulto , Pressão Intraocular/fisiologia , Iris/diagnóstico por imagem , Iris/patologia , Malha Trabecular/diagnóstico por imagem , Malha Trabecular/patologia , Idoso de 80 Anos ou mais , Adulto JovemRESUMO
BACKGROUND: Myopia, characterized by excessive axial elongation of the eyeball, increases risks of having sight-threatening diseases and impose a financial burden to healthcare system. Although myopic control interventions showed their effectiveness in slowing progression, the efficacy varies between individuals and does not completely halt progression. The study aims to investigate the efficacy of combining 0.01% atropine administered twice daily with optical defocus for myopia control in schoolchildren. METHODS AND DESIGN: This is a prospective, parallel-group, single-blinded, randomized, active-control trial (ClinicalTrials.gov identifier: NCT06358755). Myopic schoolchildren with no previous myopic control interventions aged between 7 to 12 years will be recruited. They will be randomly allocated into two groups (n = 56 per group) after baseline measurement. Both groups will receive 0.01% atropine twice per day for 18 months (one drop in the morning and the other drop at night before bedtime). Defocus incorporated multiple segments (DIMS) spectacle lenses will be prescribed in atropine plus optical defocus (ATD) treatment group while single vision spectacle lenses will be given in atropine only (AT) group. Cycloplegic refraction and axial lengths will be monitored every 6 months over 18-month study period. The primary outcomes are changes in cycloplegic refraction and axial lengths relative to the baseline over the study period. DISCUSSION: The result will examine the combination effect of low dose atropine and myopic defocus on myopia control in a randomized controlled study. The findings will also explore the potential benefits of applying 0.01% atropine twice per day on myopic control and its potential side effects.
Assuntos
Atropina , Miopia , Humanos , Atropina/administração & dosagem , Miopia/tratamento farmacológico , Miopia/prevenção & controle , Criança , Estudos Prospectivos , Masculino , Feminino , Refração Ocular/efeitos dos fármacos , Refração Ocular/fisiologia , Óculos , Método Simples-Cego , Soluções Oftálmicas/administração & dosagem , Midriáticos/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: The crystalline lens is a transparent structure of the eye to focus light on the retina. It becomes muddy, hard and dense with increasing age, which makes the crystalline lens gradually lose its function. We aim to develop a nuclear age predictor to reflect the degeneration of the crystalline lens nucleus. METHODS: First we trained and internally validated the nuclear age predictor with a deep-learning algorithm, using 12 904 anterior segment optical coherence tomography (AS-OCT) images from four diverse Asian and American cohorts: Zhongshan Ophthalmic Center with Machine0 (ZOM0), Tomey Corporation (TOMEY), University of California San Francisco and the Chinese University of Hong Kong. External testing was done on three independent datasets: Tokyo University (TU), ZOM1 and Shenzhen People's Hospital (SPH). We also demonstrate the possibility of detecting nuclear cataracts (NCs) from the nuclear age gap. FINDINGS: In the internal validation dataset, the nuclear age could be predicted with a mean absolute error (MAE) of 2.570 years (95% CI 1.886 to 2.863). Across the three external testing datasets, the algorithm achieved MAEs of 4.261 years (95% CI 3.391 to 5.094) in TU, 3.920 years (95% CI 3.332 to 4.637) in ZOM1-NonCata and 4.380 years (95% CI 3.730 to 5.061) in SPH-NonCata. The MAEs for NC eyes were 8.490 years (95% CI 7.219 to 9.766) in ZOM1-NC and 9.998 years (95% CI 5.673 to 14.642) in SPH-NC. The nuclear age gap outperformed both ophthalmologists in detecting NCs, with areas under the receiver operating characteristic curves of 0.853 years (95% CI 0.787 to 0.917) in ZOM1 and 0.909 years (95% CI 0.828 to 0.978) in SPH. INTERPRETATION: The nuclear age predictor shows good performance, validating the feasibility of using AS-OCT images as an effective screening tool for nucleus degeneration. Our work also demonstrates the potential use of the nuclear age gap to detect NCs.
Assuntos
Catarata , Cristalino , Humanos , Pré-Escolar , Lactente , Cristalino/diagnóstico por imagem , Catarata/diagnóstico , Retina , Algoritmos , Tomografia de Coerência Óptica/métodosRESUMO
PURPOSE: To investigate factors associated with the severity of prelaminar schisis (PLS) in heathy subjects and glaucoma patients. DESIGN: Prospective cross-sectional study. METHODS: A total of 217 eyes of 217 subjects (110 normal eyes and 107 open angle glaucoma eyes) were studied. Frequency and severity of PLS were compared between normal and glaucomatous eyes. Multivariate logistic models were used to assess factors associated with the severity of PLS. Factors considered were age, axial length, glaucomatous damage indices, Bruch membrane opening (BMO) and anterior scleral canal opening parameters, tractional forces (posterior vitreous staging and presence of Bergmeister papilla), circumpapillary choroidal thickness, lamina cribrosa (LC) parameters, and peripapillary scleral (PPS) angle. RESULTS: The frequency of PLS was 70.9% in normal eyes and 72.0% in glaucomatous eyes. There was no difference in frequency and severity between the groups. The presence of Bergmeister papilla was the strongest predictor of a more severe PLS in both normal and glaucomatous eyes (odds ratio [OR] + 9.78, 12.5; both P < .001). A larger PPS angle in normal eyes (OR = 1.19; P = .003) and a larger BMO area and a deeper LC depth in glaucomatous eyes (OR = 1.08, 1.05; both P = .038) were associated with severity of PLS. CONCLUSIONS: The severity of PLS was strongly associated with the presence of Bergmeister papilla, suggesting a traction-related phenomenon. Correlation of PLS severity with larger BMO area and deeper LC depth, which are optic nerve head structures associated with glaucoma, suggested its possible relationship with glaucomatous damage.
Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Disco Óptico , Vítreo Primário Hiperplásico Persistente , Humanos , Glaucoma de Ângulo Aberto/complicações , Glaucoma de Ângulo Aberto/diagnóstico , Estudos Transversais , Estudos Prospectivos , Tomografia de Coerência Óptica , Glaucoma/complicações , Glaucoma/diagnóstico , Pressão IntraocularRESUMO
PURPOSE: To explore the effects of deep optic nerve head (ONH) structures on Bruch's membrane opening (BMO)-minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness (pRNFLT) in healthy eyes. DESIGN: Prospective cross-sectional study. METHODS: Two hundred five healthy eyes of 141 subjects (mean ± standard deviation of age and axial length (AXL): 46.9 ± 10.0 years and 24.79 ± 1.15 mm) were enrolled. Best fit multivariable linear mixed models identified factors associated with BMO-MRW and pRNFLT. Explanatory variables included age, gender, AXL, BMO and anterior scleral canal opening (ASCO) area and ovality, magnitude of BMO and ASCO shift, peripapillary choroidal thickness, lamina cribrosa (LC) parameters, prelaminar thickness, and peripapillary scleral (PPS) angle. RESULTS: Thinner BMO-MRW was associated with older age, smaller ASCO/BMO offset magnitude, larger BMO area, thinner prelaminar thickness, deeper LC, and thinner pRNFLT (P = .011, <.001, .004, <.001, <.001, <.001 respectively). Thinner pRNFLT was associated with shorter AXL, smaller ASCO area, a more posteriorly bowed PPS, shallower LC and thinner BMO-MRW. (P = .030, .002, .035, .012, <.001 respectively) CONCLUSIONS: BMO-MRW and pRNFLT were influenced by several deep ONH structures such as BMO and ASCO position shift, BMO or ASCO area, prelaminar thickness, PPS bowing and LC depth in addition to patient characteristics such as age and AXL. The degree and/or direction of associations varied between deep ONH structures and BMO-MRW or pRNFLT. Despite both BMO-MRW and pRNFLT being surrogate parameters for RGC loss, a complex relationship with ONH deep-layer morphology was indicated.
Assuntos
Lâmina Basilar da Corioide , Pressão Intraocular , Fibras Nervosas , Disco Óptico , Células Ganglionares da Retina , Tomografia de Coerência Óptica , Humanos , Lâmina Basilar da Corioide/patologia , Disco Óptico/patologia , Disco Óptico/diagnóstico por imagem , Disco Óptico/anatomia & histologia , Feminino , Masculino , Estudos Transversais , Estudos Prospectivos , Pessoa de Meia-Idade , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica/métodos , Fibras Nervosas/patologia , Adulto , Pressão Intraocular/fisiologia , Idoso , Comprimento Axial do Olho/patologia , Campos Visuais/fisiologia , Voluntários SaudáveisRESUMO
OBJECTIVE: To measure iris volume and anterior segment parameters using a swept-source anterior segment optical coherence tomography (OCT) and investigate factors associated with iris volume and iris volume change after pupil dilation in eyes with open angles and angle closure. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 86 eyes, including 31 eyes from 21 patients with primary angle closure (PAC) or PAC suspect, 31 eyes from 20 patients with primary open-angle glaucoma (POAG), and 24 eyes from 15 normal subjects, were included. METHODS: The anterior segment parameters and iris were imaged and measured by the Casia SS-1000 OCT (Tomey, Nagoya, Japan) in room light, dark, and after pharmacologic dilation. Linear mixed models were used to examine the association between iris volume and change in iris volume after dilation and each of the following: age, sex, anterior chamber volume (ACV), axial length, pupil diameter, and angle width. MAIN OUTCOME MEASURES: Iris volume. RESULTS: The mean iris volume significantly decreased from light to dark and after pharmacologic dilation in angle closure (40.0 ± 5.2, 38.8 ± 5.4, and 32.5 ± 4.5 mm(3), respectively), POAG (40.2 ± 5.3, 39.4 ± 5.4, and 33.6 ± 4.2 mm(3), respectively), and normal eyes (40.1 ± 4.2, 39.1 ± 3.9, and 33.0 ± 4.4 mm(3), respectively). From room light to dark, the iris volume of 16.7% normal, 19.4% POAG, and 19.4% angle closure eyes increased iris volume (P = 0.960). After pharmacologic dilation, iris volume decreased in all eyes. Iris volume was negatively associated with ACV and positively associated with axial length (P<0.001). The change in iris volume per millimeter change in pupil diameter was 2.11, 2.01, and 1.80 mm(3)/mm in the angle closure, POAG, and normal groups, respectively (P≥0.414). A smaller ACV (P = 0.049) and older age (P = 0.036) were associated with a smaller change in iris volume per millimeter change in pupil diameter. A larger iris volume, smaller ACV, and greater pupil diameter were significant determinants of a smaller angle width (all P≤0.003). CONCLUSIONS: The mean iris volume decreased after pupil dilation in open-angle and angle closure eyes, and the degree of reduction was less in eyes with a smaller ACV. Both iris volume and ACV were important determinants of the anterior chamber angle.
Assuntos
Glaucoma de Ângulo Fechado/patologia , Iris/patologia , Tomografia de Coerência Óptica , Idoso , Segmento Anterior do Olho/patologia , Visão de Cores , Estudos Transversais , Combinação de Medicamentos , Feminino , Glaucoma de Ângulo Aberto/patologia , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Midriáticos/administração & dosagem , Visão Noturna , Variações Dependentes do Observador , Fenilefrina/administração & dosagem , Pupila/efeitos dos fármacos , Reprodutibilidade dos Testes , Tonometria Ocular , Tropicamida/administração & dosagemRESUMO
BACKGROUND: The loss of RGCs expressing Thy-1 after optic nerve injury has an initial phase of rapid decline followed by a longer phase with slower reduction rate. This study used longitudinal retinal imaging of mice expressing cyan fluorescent protein under control of the Thy-1 promoter (Thy1-CFP mice) to determine how the α2-adrenergic agonist brimonidine influences loss of Thy1 promoter activation. METHODS: Baseline images of the fluorescent retinal neurons in 30 Thy1-CFP mice were obtained using a modified confocal scanning laser ophthalmoscope. Next, brimonidine (100 ug/kg, IP) was administered either one time immediately after optic nerve crush, or immediately after optic nerve crush and then every 2 days for four weeks. A control group received a single saline injection immediately after optic nerve crush. All animals were imaged weekly for four weeks after optic nerve crush. Loss of fluorescent retinal neurons within specific retinal areas was determined by counting. RESULTS: At one week after optic nerve crush, the proportion of fluorescent retinal neurons retaining fluorescence was 44±7% of baseline in control mice, 51±6% after one brimonidine treatment, and 55±6% after brimonidine treatment every other day (P<0.05 for both brimonidine treatment groups compared to the control group). Subsequently, the number of fluorescent retinal neurons in the group that received one treatment differed insignificantly from the control group. In contrast, the number of fluorescent retinal neurons in the group that received repeated brimonidine treatments was greater than the control group by 28% at two weeks after crush and by 32% at three weeks after crush (P<0.05 at both time points). Rate analysis showed that brimonidine slowed the initial rate of fluorescent cell decline in the animals that received multiple treatments (P<0.05). Differences in the rate of loss among the treatment groups were insignificant after the second week. CONCLUSION: Repeated brimonidine treatments protect against loss of fluorescence within fluorescent retinal neurons of Thy1-CFP mice after optic nerve crush. As most of fluorescent retinal neurons in this system are RGCs, these findings indicate that repeated brimonidine treatments may protect RGC health following optic nerve crush.
Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Compressão Nervosa , Traumatismos do Nervo Óptico/tratamento farmacológico , Regiões Promotoras Genéticas , Substâncias Protetoras/uso terapêutico , Quinoxalinas/uso terapêutico , Antígenos Thy-1/fisiologia , Análise de Variância , Animais , Tartarato de Brimonidina , Contagem de Células , Modelos Animais de Doenças , Feminino , Estudos Longitudinais , Masculino , Camundongos , Microscopia de Fluorescência , Traumatismos do Nervo Óptico/genética , Traumatismos do Nervo Óptico/patologia , Células Ganglionares da Retina/efeitos dos fármacosRESUMO
AIMS: To apply a deep learning model for automatic localisation of the scleral spur (SS) in anterior segment optical coherence tomography (AS-OCT) images and compare the reproducibility of anterior chamber angle (ACA) width between deep learning located SS (DLLSS) and manually plotted SS (MPSS). METHODS: In this multicentre, cross-sectional study, a test dataset comprising 5166 AS-OCT images from 287 eyes (116 healthy eyes with open angles and 171 eyes with primary angle-closure disease (PACD)) of 287 subjects were recruited from four ophthalmology clinics. Each eye was imaged twice by a swept-source AS-OCT (CASIA2, Tomey, Nagoya, Japan) in the same visit and one eye of each patient was randomly selected for measurements of ACA. The agreement between DLLSS and MPSS was assessed using the Euclidean distance (ED). The angle opening distance (AOD) of 750 µm (AOD750) and trabecular-iris space area (TISA) of 750 µm (TISA750) were calculated using the CASIA2 embedded software. The repeatability of ACA width was measured. RESULTS: The mean age was 60.8±12.3 years (range: 30-85 years) for the normal group and 63.4±10.6 years (range: 40-91 years) for the PACD group. The mean difference in ED for SS localisation between DLLSS and MPSS was 66.50±20.54 µm and 84.78±28.33 µm for the normal group and the PACD group, respectively. The span of 95% limits of agreement between DLLSS and MPSS was 0.064 mm for AOD750 and 0.034 mm2 for TISA750. The respective repeatability coefficients of AOD750 and TISA750 were 0.049 mm and 0.026 mm2 for DLLSS, and 0.058 mm and 0.030 mm2 for MPSS. CONCLUSION: DLLSS achieved comparable repeatability compared with MPSS for measurement of ACA.
Assuntos
Aprendizado Profundo , Glaucoma de Ângulo Fechado , Humanos , Pessoa de Meia-Idade , Idoso , Esclera/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Estudos Transversais , Reprodutibilidade dos Testes , Câmara Anterior/diagnóstico por imagem , Iris , Segmento Anterior do Olho/diagnóstico por imagem , Glaucoma de Ângulo Fechado/diagnóstico por imagem , Gonioscopia , Pressão IntraocularRESUMO
PURPOSE: To elucidate which swept-source optical coherence tomography (OCT)-derived optic nerve head (ONH) parameters are associated with longer axial length (AXL) in healthy myopic eyes. DESIGN: Prospective cross-sectional observational study. METHODS: Two hundred eleven healthy eyes of 140 participants (96 emmetropic-mild myopic [AXL: 22.2-24.5 mm], 83 moderately myopic [24.5-26.0 mm], and 32 highly myopic [26.0-27.4 mm] eyes) were enrolled. Bruch membrane opening (BMO), anterior scleral canal opening (ASCO) area and ovality, minimum rim width, parameters defining misalignment between the BMO and ASCO planes, OCT-defined region of perineural canal retinal epithelium atrophy and externally oblique choroidal border tissue, circumpapillary retinal nerve fiber layer thickness (cpRNFLT), circumpapillary choroidal thickness (cpChT), lamina cribrosa parameters, and peripapillary scleral (PPS) angle were calculated from BMO-centered radial scans reconstructed from 3D raster scans. Multivariate linear mixed models were used to elucidate ONH parameters that are independently associated with AXL. RESULTS: Longer AXL was associated with a greater misalignment between ASCO and BMO planes, larger region of externally oblique choroidal border tissue, thinner cpChT, larger PPS angle, larger ASCO area, and thicker cpRNFLT (all P < .040 after Bonferroni's correction for number of included explanatory variables). CONCLUSIONS: A greater misalignment between BMO and ASCO planes, thinner choroid, a more posteriorly bowed PPS, an enlargement of ASCO, and thicker cpRNFLT were each associated with longer AXL. An enhanced understanding of these AXL-associated configurations should provide essential information to improve our ability to detect glaucoma-induced ONH morphology in myopic eyes.
Assuntos
Glaucoma , Miopia , Disco Óptico , Humanos , Estudos Transversais , Estudos Prospectivos , Miopia/diagnóstico , Lâmina Basilar da Corioide , Tomografia de Coerência Óptica/métodos , Pressão IntraocularRESUMO
OBJECTIVE: To evaluate the agreement of optic disc measurements obtained with the Cirrus high-density optical coherence tomography (HD-OCT) and the Heidelberg retina tomograph (HRT) and compare the intervisit, test-retest variability between the instruments. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: Two hundred seven subjects (109 glaucoma and 98 normal subjects). METHODS: One eye from each individual was selected randomly for optic disc imaging by the Cirrus HD-OCT and the HRT. Areas of the optic disc and the cup, cup volume, vertical cup-to-disc ratio and cup-to-disc area ratio were compared between the instruments. The OCT measurements were corrected for ocular magnification using the Littman's formula. The measurement agreement was evaluated with the Bland-Altman plots. The intervisit test-retest variability was examined in 17 randomly selected glaucoma patients who underwent optic disc imaging weekly for 8 consecutive weeks. The intraclass correlation coefficients (ICC) and the reproducibility coefficients of the optic disc parameters were computed. MAIN OUTCOME MEASURES: Measurement agreement, reproducibility coefficients, and ICCs of optic disc parameters. RESULTS: The OCT measured smaller optic disc and rim areas and greater cup volume, vertical cup-to-disc ratio and cup-to-disc area ratio than the HRT did (all with P<0.001). There were proportional biases in the Bland-Altman plots between OCT and HRT optic disc measurements except for rim area and cup-to-disc area ratio. The 95% limits of agreement of rim area ranged between -0.28 and 0.88 mm(2) before, and between -0.22 and 0.92 mm(2) after correction for ocular magnification. Both OCT and HRT showed high test-retest reproducibility with ICCs ≥ 0.921. Although the reproducibility coefficient of OCT rim area (0.093 mm(2); 95% confidence interval [CI], 0.081-0.105 mm(2)) was significantly smaller than that of the HRT (0.186 mm(2); 95% CI, 0.163-0.210 mm(2); P = .018), there were no differences in the ICCs between the instruments. CONCLUSIONS: Optic disc assessment by spectral-domain OCT and confocal scanning laser ophthalmoscopy demonstrates poor agreement but similarly low test-retest variability. The source of their disagreement and its effects on the detection of progression require further study.
Assuntos
Axônios/patologia , Técnicas de Diagnóstico Oftalmológico/normas , Glaucoma/diagnóstico , Disco Óptico/patologia , Doenças do Nervo Óptico/diagnóstico , Células Ganglionares da Retina/patologia , Estudos Transversais , Feminino , Humanos , Pressão Intraocular , Masculino , Microscopia Confocal/normas , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tomografia de Coerência Óptica/normas , Transtornos da Visão/diagnóstico , Testes de Campo Visual , Campos VisuaisRESUMO
OBJECTIVE: To examine the use of the retinal nerve fiber layer (RNFL) thickness map generated by a spectral-domain optical coherence tomography (OCT) to detect RNFL progression and identify the pattern of progressive changes of RNFL defects in glaucoma. DESIGN: Prospective, longitudinal study. PARTICIPANTS: One hundred eighty-six eyes of 103 glaucoma patients. METHODS: Patients were followed at 4-month intervals for ≥ 36 months for RNFL imaging and visual field examination. Both eyes were imaged by the Cirrus HD-OCT (Carl Zeiss Meditec Inc., Dublin, CA) and had visual field testing at the same visits. We defined RNFL progression by Guided Progression Analysis (Carl Zeiss Meditec) of serial RNFL thickness maps. The pattern of RNFL progression was evaluated by comparing the baseline RNFL thickness deviation map and the RNFL thickness change map. Visual field progression was defined by trend analysis of visual field index and event analysis based on the Early Manifest Glaucoma Trial criteria. MAIN OUTCOME MEASURES: The presence and the pattern of RNFL progression. RESULTS: A total of 2135 OCT images were reviewed. Twenty-eight eyes (15.1%) from 24 patients (23.3%) had RNFL progression detected by RNFL thickness map analysis. Three RNFL progression patterns were observed: (1) widening of RNFL defects (24 eyes, 85.7%), (2) deepening of RNFL defects (2 eyes, 7.1%, both had concomitant widening of RNFL defects), and (3) development of new RNFL defects (5 eyes, 17.9%). The inferotemporal meridian (324°-336°) 2.0 mm away from the optic disc center was the most frequent location where RNFL progression was detected. Thirteen eyes (46.4%) had concomitant visual field progression; 61.5% (n = 8) of these had RNFL progression that preceded or occurred concurrently with visual field progression. Forty-two eyes from 37 patients (22.6%) had visual field progression by trend and/or event analyses without progression in the RNFL thickness map. CONCLUSIONS: Analysis of serial RNFL thickness maps generated by the spectral-domain OCT facilitates the detection of RNFL progression in glaucoma.
Assuntos
Axônios/patologia , Glaucoma/diagnóstico , Disco Óptico/patologia , Doenças do Nervo Óptico/diagnóstico , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica , Progressão da Doença , Feminino , Gonioscopia , Humanos , Pressão Intraocular , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transtornos da Visão , Testes de Campo Visual , Campos VisuaisRESUMO
BACKGROUND: Whereas lowering the intraocular pressure (IOP) can slow optic nerve degeneration in glaucoma, many patients with glaucoma continue to develop progressive loss in vision despite a significant reduction in IOP. No treatment has been shown to be effective for neuroprotection in glaucoma. We set out to conduct a randomized controlled trial to investigate whether nicotinamide riboside (NR), a nicotinamide adenine dinucleotide precursor, is effective to slow optic nerve degeneration in patients with primary open-angle glaucoma (POAG). We hypothesize that patients treated with NR have a slower rate of progressive retinal nerve fiber layer (RNFL) thinning compared with those treated with placebo. METHODS: This is a randomized, double-blind, placebo-controlled, parallel-group, multi-center study including 125 patients with POAG. Patients will be randomized to receive 300 mg NR or placebo for 24 months. Clinical examination, optical coherence tomography imaging of the RNFL, and visual field (VF) test will be performed at the baseline, 1 month, 4 months, and then at 2-month intervals until 24 months. The primary outcome measure is the rate of RNFL thinning measured over 24 months. The secondary outcome measures include (1) time to VF progression, (2) time to progressive RNFL/ganglion cell inner plexiform layer (GCIPL) thinning, and (3) the rate of change of VF sensitivity over 24 months (to investigate neuroprotection) and 1 month (to investigate neuroenhancement). The rates of RNFL thinning and VF sensitivity decline between treatment groups will be compared with linear mixed modeling. Survival analysis will be performed to compare the differences in time from baseline to VF progression and time from baseline to progressive RNFL/GCIPL thinning between treatment groups using Cox proportional hazards models. DISCUSSION: Outcome measures in glaucoma neuroprotection trials have been centered on the detection of VF progression, which may take years to develop and confirm. In addition to addressing whether NR has a neuroprotective/neuroenhancement effect in glaucoma patients, this study will demonstrate the feasibility of studying neuroprotection in a relatively short trial period (24 months) by comparing the rates of progressive RNFL thinning, a more reproducible and objective outcome measure compared with VF endpoints, between treatment groups. TRIAL REGISTRATION: Chinese Clinical Trial Registry 1900021998.