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PURPOSE: To compare optical coherence tomography-measured Bruch membrane opening minimum rim width (MRW), peripapillary retinal nerve fiber layer (pRNFL) measurements, and MRW:pRNFL ratios in eyes with compressive optic neuropathy (CON) and glaucoma and controls, and evaluate the ability of these parameters to differentiate CON from glaucoma. DESIGN: Prospective, cross-sectional study. METHODS: Setting: Single-center tertiary hospital and outpatient clinic. PATIENT POPULATION: One hundred fifteen eyes of 77 participants, 34 with CON from chiasmal lesions, 21 with glaucoma, and 22 healthy controls. OBSERVATION PROCEDURES: Optical coherence tomography-measured MRW, pRNFL, and MRW:pRNFL ratios for each optic disc sector and global average. MAIN OUTCOME MEASURES: MRW, pRNFL, and MRW:pRNFL ratios compared using generalized estimated equations. Area under the receiver operating characteristic curve and positive and negative likelihood ratios were calculated. RESULTS: MRW and pRNFL measurements were significantly reduced in CON and glaucoma compared with controls. In glaucoma, MRW was thinner than in CON in the global, inferotemporal, superonasal, inferonasal, and vertical average measurements, but a significant overlap was observed in many parameters. MRW:pRNFL ratios increased the ability to discriminate between CON and glaucoma, as shown by the high area under the receiver operating characteristic curve, high positive likelihood ratios, and low negative likelihood ratios, especially in the nasal disc sector and the nasal and temporal average. CONCLUSIONS: MRW measurements alone cannot reliably distinguish CON from glaucoma, but the combination of MRW, pRNFL, and MRW:pRNFL ratios significantly improves accuracy. When comparing the 2 conditions, MRW:pRNFL ratios yielded higher area under the receiver operating characteristic curve and positive and negative likelihood ratios, suggesting this parameter may be helpful in clinical practice.

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PURPOSE: To determine whether the glaucoma diagnostic accuracy of age- and Bruch membrane opening area (BMOA)-adjusted normative classifications of minimum rim width (MRW) and retinal nerve fiber layer thickness (RNFLT) is dependent on BMOA, in a European descent population. DESIGN: Retrospective, cross-sectional study. METHODS: We included 182 glaucoma patients and 166 healthy controls for the primary study, and 105 glaucoma patients in a second sample used for a replication study. Optical coherence tomography (Spectralis) measurements of BMOA, global MRW, and RNFLT and normative classifications from the device software were exported for analysis. Sensitivity and specificity were calculated for a conservative criterion (abnormal = "outside normal limits" classification) and a liberal criterion (abnormal = "outside normal limits" or "borderline" classifications). The dependence of sensitivity and specificity on BMOA was analyzed with comparison among subgroups divided by tertiles of BMOA, and with logistic regression. RESULTS: For the conservative criterion, MRW sensitivity was independent of BMOA (P ≥ .76), while RNFLT sensitivity increased in the large BMOA subgroup (P = .04, odds ratio: 1.2 per mm2 [P = .02]). For the liberal criterion, MRW and RNFLT sensitivities were independent of BMOA (P ≥ .53). Specificities were independent of BMOA (P ≥ .07). For the replication sample, which included younger patients with larger BMOA and worse visual field damage than the primary sample, sensitivities were independent of BMOA for both criteria (P ≥ .10). CONCLUSIONS: RNFLT sensitivity was higher in eyes with larger BMOA; however, age and visual field damage may influence that association. MRW diagnostic accuracy was not dependent on BMOA.

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BACKGROUND: To investigate structural and functional correlations in glaucoma patients using enhanced depth imaging spectral-domain optical coherence tomography (EDI OCT)-derived parameters. METHODS: We prospectively enrolled healthy participants and glaucomatous patients with a wide range of disease stages. All participants underwent visual field (VF) testing (SITA - Standard 24-2; Carl Zeiss Meditec, Dublin, CA) and EDI OCT imaging (Spectralis; Heidelberg Engineering Co., Heidelberg, Germany). The following optic nerve head parameters were measured on serial vertical EDI OCT B-scans by two experienced examiners masked to patients clinical data: lamina cribrosa (LC) thickness and area, prelaminar neural tissue thickness and area, anterior LC depth, Bruch's membrane opening (BMO) and average, superior, and inferior BMO-minimum rim width (BMO-MRW). Only good quality images were considered, and whenever both eyes were eligible, one was randomly selected for analysis. Scatter plots were constructed to investigate correlations between each anatomic parameter and patient's VF status (based on VF index [VFI] values). RESULTS: A total of 73 eyes of 73 patients were included. All EDI OCT parameters evaluated differed significantly between glaucomatous and control eyes (P ≤ 0.045). A secondary analysis, in which glaucomatous patients were divided according to VF mean deviation index values into 3 groups (mild [G1; > - 6 dB], moderate [G2; - 6 to - 12 dB] and advanced [G3; <- 12 dB] glaucoma), revealed that average BMO-MRW was the EDI OCT parameter that presented more significant differences between the different stages of glaucoma. Significant structure-function correlations were found between VFI values and prelaminar neural tissue area (R2 = 0.20, P = 0.017), average BMO-MRW (R2 = 0.35, P ≤ 0.001), superior BMO-MRW (R2 = 0.21, P = 0.012), and inferior BMO-MRW (R2 = 0.27, P = 0.002). No significant correlations were found for LC area and anterior LC depth (P ≥ 0.452). CONCLUSIONS: Evaluating the distribution pattern and structure-function correlations of different laminar and prelaminar EDI OCT-derived parameters in glaucomatous patients, we found better results for neural tissue-based indexes (compared to LC-derived parameters). The diagnostic utility of each parameter deserves further investigations.

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Non-exudative age-related macular degeneration, a prevalent cause of blindness, is a progressive and degenerative disease characterized by alterations in Bruch's membrane, retinal pigment epithelium, and photoreceptors exclusively localized in the macula. Although experimental murine models exist, the vast majority take a long time to develop retinal alterations and, in general, these alterations are ubiquitous, with many resulting from non-eye-specific genetic manipulations; additionally, most do not always reproduce the hallmarks of human age-related macular degeneration. Choroid vessels receive sympathetic innervation from the superior cervical ganglion, which, together with the parasympathetic system, regulates blood flow into the choroid. Choroid blood flow changes have been involved in age-related macular degeneration development and progression. At present, no experimental models take this factor into account. The aim of this work was to analyze the effect of superior cervical gangliectomy (also known as ganglionectomy) on the choroid, Bruch's membrane, retinal pigment epithelium and retina. Adult male C57BL/6J mice underwent unilateral superior cervical gangliectomy and a contralateral sham procedure. Although superior cervical gangliectomy induced ubiquitous choroid and choriocapillaris changes, it induced Bruch's membrane thickening, loss of retinal pigment epithelium melanin content and retinoid isomerohydrolase, the appearance of drusen-like deposits, and retinal pigment epithelium and photoreceptor atrophy, exclusively localized in the temporal side. Moreover, superior cervical gangliectomy provoked a localized increase in retinal pigment epithelium and photoreceptor apoptosis, and a decline in photoreceptor electroretinographic function. Therefore, superior cervical gangliectomy recapitulated the main features of human non-exudative age-related macular degeneration, and could become a new experimental model of dry age-related macular degeneration, and a useful platform for developing new therapies.

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Purpose: The mutation R345W in EFEMP1 (fibulin-3) causes macular degeneration. This study sought to determine whether proteoglycan content and diffusion across Bruch's membrane are altered in Efemp1ki/ki mice carrying this mutation or in Efemp1-/- mice. Methods: Proteoglycans in mouse Bruch's membranes were stained with Cupromeronic Blue (CB). Heparan sulfated proteoglycan (HSPG) and chondroitin/dermatan sulfate proteoglycan (C/DSPG) distributions were visualized following treatments with chondroitinase ABC (C-ABC) or nitrous acid. Total sulfated glycosaminoglycans (sGAGs) in Bruch's membrane/choroid (BrM/Ch) were measured with dimethylmethylene blue (DMMB). Matrix metalloprotease (MMP)-2, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-3 were examined by immunofluorescence and quantified using Image J. Molecules with different Stokes radius (Rs) were allowed simultaneously to diffuse through mouse BrM/Ch mounted in a modified Ussing chamber. Samples were quantified using gel exclusion chromatography. Results: HSPGs and C/DSPGs were markedly increased in Efemp1ki/ki Bruch's membrane, and MMP-2 and MMP-9 were decreased, but TIMP-3 was increased. Diffusion across Efemp1ki/ki Bruch's membrane was impaired. In contrast, the proteoglycan amount in Efemp1-/- Bruch's membrane was not significantly different, but the size of proteoglycans was much larger. MMP-2, MMP-3, and TIMP-3 levels were similar to that of Efemp1+/+ mice, but they were localized diffusely in retinal pigment epithelium (RPE) cells instead of Bruch's membrane. Diffusion across Efemp1-/- Bruch's membrane was enhanced. Conclusions: Mutant fibulin-3 causes proteoglycan accumulation, reduction of MMP-2 and MMP-9, but increase of TIMP-3, and impairs diffusion across Bruch's membrane. Fibulin-3 ablation results in altered sizes of proteoglycans, altered distributions of MMP-2, MMP-9, and TIMP-3, and enhances diffusion across Bruch's membrane.

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PURPOSE: To investigate the reproducibility of Bruch's membrane opening minimum rim width (BMO-MRW) and retinal nerve fibre layer thickness (RNFLT) measurements using spectral domain optical coherence tomography (SD-OCT). Additionally, to investigate the reproducibility of BMO area measurements and fovea to BMO centre (FoBMO) angle. METHODS: Participants were healthy subjects (n = 30) and patients with glaucoma (n = 26). One eye of each participant was scanned to obtain optic nerve head (24 radial B-scans) and peripapillary (one circular B-scan) images by three independent examiners. Additionally, one examiner imaged each participant three times on the same day. Intra- and interobserver reproducibilities were estimated by within-subject standard deviation (SW) and coefficient of variation (COV). Spearman's rank correlation coefficient was used to test the correlation between the magnitude of the parameter and its standard deviation. RESULTS: The global BMO-MRW COVs (%) in healthy/glaucoma subjects were 0.87/1.34 and 1.28/3.13 for intra- and interobserver analyses, respectively, and the corresponding global RNFLT figures were 1.50/2.10 and 2.04/2.87. Global mean BMO-MRW and RNFLT showed no correlation with their respective standard deviations. The reproducibilities of BMO area and FoBMO angle were excellent and similar between the groups. CONCLUSION: The reproducibilities of BMO-MRW, BMO area measurements and FoBMO angle were excellent in both healthy subjects and patients with glaucoma. Bruch's membrane opening minimum rim width (BMO-MRW) reproducibility is comparable to that of RNFLT measurements.

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Os autores relatam quatro casos de estrias angióides associadas com pseudoxantoma elástico (Síndrome de Gronblad-Strandberg) diagnosticados no Serviço de Oftalmologia do HCPA. Discutem as alteraçöes sistêmicas encontradas e enfatizam a importância do diagnóstico precoce e do acompanhamento oftalmológico destes pacientes.

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