PURPOSE: We sought to investigate the effects of Graves' orbitopathy (GO) and orbital decompression on lamina cribrosa depth (LCD) using spectral-domain optical coherence tomography. METHODS: Forty eyes that underwent orbital decompression to relieve compressive optic neuropathy or correct disfiguring exophthalmos in the context of GO were included. Subjects were imaged with spectral-domain optical coherence tomography before surgery and at 1 and 3 months after surgery, at which the examiner measured the LCD (distance from the anterior surface of the lamina cribrosa to the Bruch membrane opening line) and peripapillary retinal nerve fiber layer thickness. Subjects were divided into two groups—a muscle-dominant group composed of patients who had extraocular muscle enlargement on preoperative orbital computed tomography scan and a fat-dominant group composed of patients who did not show extraocular muscle enlargement on preoperative orbital computed tomography scan—and subgroup analysis was performed. Preoperative and postoperative intraocular pressure, exophthalmos, LCD, and retinal nerve fiber layer thickness were evaluated. RESULTS: At baseline, LCD was remarkably shallower in the muscle-dominant group than in the fat-dominant group (95% confidence interval, p = 0.007). In the muscle-dominant group, LCD showed no definite change after surgery. However, the fat-dominant group showed temporary posterior displacement of the lamina cribrosa at 1-month postoperation that was reversed to baseline at 3 months postoperation (95% confidence interval, p < 0.01). CONCLUSIONS: The lamina cribrosa was anteriorly displaced preoperatively, and its position was nearly unchanged after the surgery, especially in association with extraocular muscle enlargement. An enlarged extraocular muscle could reduce the pressure-relieving effect of orbital decompression around the scleral canal in patients with GO.
Bruch Membrane ; Decompression ; Exophthalmos ; Graves Ophthalmopathy ; Humans ; Intraocular Pressure ; Nerve Fibers ; Optic Nerve ; Optic Nerve Diseases ; Orbit ; Retinaldehyde ; Tomography, Optical Coherence

PURPOSE: To explore the progressive change and associated factors of optic disc tilt in young myopic glaucomatous eyes by analyzing long-term follow-up data.METHODS: Optic disc images were obtained from spectral-domain optical coherence tomography enhanced depth imaging from at least five different visits. At each visit, the disc tilt angle (DTA), defined as the angle between the Bruch's membrane opening plane and the optic canal plane, was estimated at the central frame that passes through the optic disc. Glaucoma progression was assessed on the basis of changes noted on serial optic disc and retinal nerve fiber layer photographs or changes in the visual field (VF). A linear mixed effect model was used to assess the influence of parameters (age, sex, baseline and follow-up intraocular pressure, retinal nerve fiber layer thickness, VF mean deviation, axial length, central corneal thickness), and presence of glaucomatous progression upon DTA change.RESULTS: A total of 26 eyes of 26 young myopic primary open-angle glaucoma patients (axial length >24.0 mm; mean age, 25.1 ± 4.0 years; mean follow-up, 3.3 ± 0.9 years) were included. DTA was 7.0 ± 3.4 degrees at baseline and 8.3 ± 3.8 degrees at last visit, which represents a significant difference (p < 0.001). Worse VF mean deviation (p < 0.001) and longer axial length (p = 0.006) were significantly associated with DTA increase.CONCLUSIONS: Young myopic glaucomatous eyes showed progressive optic disc tilting. Progressive optic disc tilting in young myopic glaucomatous eyes may be related to either continuous axial myopic shift or glaucomatous structural change.
Bruch Membrane ; Follow-Up Studies ; Glaucoma ; Glaucoma, Open-Angle ; Humans ; Intraocular Pressure ; Myopia ; Nerve Fibers ; Optic Disk ; Retinaldehyde ; Tomography, Optical Coherence ; Visual Fields

PURPOSE: To develop software to measure the shortest radius in curvature of Bruch's membrane from optical coherence tomography (OCT), and then to apply it to various types of eyes. METHODS: Macular OCT images consisting of 12 images of 9 mm radial scans were studied. The horizontal to vertical pixel ratios were changed to 1:1, and Bruch's membrane was marked automatically on each image. Software to measure the radius of Bruch's membrane curvature was developed. The shortest radius on each image was defined as r (mm) and the average r of 12 images was defined as R (mm). The reciprocal of R was multiplied by the constant, 337.5, which was defined as the posterior staphyloma (PS) index. RESULTS: The OCT images of five eyes were analyzed by the software, which could calculate the curvature of Bruch's membrane automatically. The PS indices were 12.7, 23.7, and 66.4 in eyes without refractive error (Case I), in the high myopic group without posterior staphyloma (Case II), and in the high myopic group with posterior staphyloma (Case V), respectively. The PS index gradually increased according to aging in a 37-year-old patient (Case IV) with mild staphyloma from 34.6 to 39.5 over 4 years. CONCLUSIONS: PS index is a novel parameter to reflect the level of posterior staphyloma, but further studies are needed to apply it to clinical patients.
Adult ; Aging ; Bruch Membrane ; Humans ; Myopia ; Radius ; Refractive Errors ; Tomography, Optical Coherence

PURPOSE: To compare the diagnostic capability of Bruch membrane opening-minimum rim width (BMO-MRW) and peripapillary retinal nerve fiber layer (RNFL) thickness for the detection of primary open angle glaucoma. METHODS: Spectral-domain optical coherence tomography (SD-OCT) with 24 radial and 1 peripapillary B-scans centered on the Bruch membrane opening (BMO) was performed. Two SD-OCT parameters were computed globally and sectorally: (1) BMO-MRW, the minimum distance between BMO and internal limiting membrane; and (2) peripapillary retinal nerve fiber layer (RNFL) thickness. The diagnostic performance of BMO-MRW and RNFL thickness were compared with receiver operating characteristic (ROC) analysis globally and sectorally. Areas under the ROC (AUC) were calculated and compared. RESULTS: One hundred fourteen eyes (52 healthy, 62 glaucomatous) of 114 participants were included. In global analyses, the performance of BMO-MRW was similar to that of RNFL thickness (AUC 0.95 [95% confidence interval {CI}, 0.91-0.99], and 0.95 [95% CI, 0.91-0.99], respectively, p=0.93). In sectoral analyses, the pair-wise comparison among the ROC curves showed no statistical difference for all sectors except for the superotemporal, superonasal, and nasal sectors, which had significantly larger AUCs in BMO-MRW compared to RNFL thickness (p=0.03, p<0.001, and p=0.03, respectively). The parameter with the largest AUC was the inferotemporal sector for both BMO-MRW and RNFL thickness (AUC 0.98 [95% CI, 0.96-1.00], and 0.98 [95% CI, 0.96-1.00], respectively, p=0.99). CONCLUSIONS: Global BMO-MRW performed as well as global RNFL thickness for detection of glaucoma. In superotemporal, superonasal and nasal sectors, regional BMO-MRW performed better than regional RNFL thickness.
Area Under Curve ; Bruch Membrane* ; Glaucoma* ; Glaucoma, Open-Angle ; Membranes ; Nerve Fibers* ; Retinaldehyde* ; ROC Curve ; Tomography, Optical Coherence

PURPOSE: To evaluate the effect of intravitreal aflibercept according to subfoveal choroidal thickness in patients with polypoidal choroidal vasculopathy (PCV). METHODS: We retrospectively analyzed the medical records of 60 eyes from 60 patients with PCV treated with intravitreal aflibercept. The patients were followed for at least 6 months after the first injection. Using software, subfoveal choroidal thickness was manually measured as the distance from the hyper-reflective line of Bruch's membrane to the chorioscleral interface on optical coherence tomography. The patients were divided into three groups based on subfoveal choroidal thickness. Visual acuity, subfoveal choroidal thickness, central macular thickness and largest pigment epithelial detachment (PED) height, polyp regression rate, and dry macula rate were evaluated to analyze the anatomical and functional outcomes. RESULTS: Baseline mean subfoveal choroidal thickness were 178.50 ± 28.42 µm in the thin group (14 eyes, 23.3%), 287.03 ± 43.58 µm in the medium group (33 eyes, 55.0%), and 379.77 ± 17.09 µm in the thick group (13 eyes, 21.7%). Baseline age, sex, visual acuity, central macular thickness, and the largest PED height did not differ significantly among the three subgroups. Only the thin group showed significant improvement of visual acuity at 6 months (p = 0.005). Subfoveal choroidal thickness, central macular thickness, and largest PED height were significantly decreased after treatment in all subgroups and did not differ among the subgroups. Compared with the other groups, the thin subfoveal choroidal thickness group showed higher polyp regression rate at 3 months and higher dry macula rate at 6 months (p = 0.013 and p = 0.004, respectively). CONCLUSIONS: Intravitreal aflibercept injection was effective for the treatment of PCV, and thin subfoveal choroidal thickness was associated with better anatomical and functional outcomes.
Bruch Membrane ; Choroid* ; Humans ; Medical Records ; Polyps ; Retrospective Studies ; Tomography, Optical Coherence ; Visual Acuity

The role of methyl-CpG binding domain protein 2 (MBD2) in an ApoE-deficient mouse model of age-related macular degeneration (AMD) was investigated. Eight-week-old Mbd2/ApoE double deficient (Mbd2(-/-) ApoE(-/-)) mice (n=12, 24 eyes, experimental group) and MBD2 (wt) ApoE(-/-) mice (n=12, 24 eyes, control group) were fed on Western-type diet for 4 months. The mice were sacrificed, and total serum cholesterol levels were analyzed and Bruch's membrane (BM) of the eyes was removed for ultrastructural observation by transmission electron microscopy. Moreover, intercellular adhesion molecule 1 (ICAM-1) immunoreactivities were evaluated by fluorescence microscopy in sections of the eyes in both groups for further understanding the function mechanism of MBD2. There was no significant difference in the total serum cholesterol levels between control group and experimental group (P>0.05). Transmission electron microscopy revealed that AMD-like lesions, various vacuoles accumulated on BM, notable outer collagenous layer deposits and dilated basal infoldings of retinal pigment epithelium (RPE) were seen in both groups, and the BM in control group was significantly thickened as compared with experimental group (P<0.05). Fluorescence micrographs exhibited the expression of ICAM-1 in choroid was higher in control group than in experimental group. We are led to conclude that MBD2 gene knockout may lead to accumulation of more deposits on the BM and influence the pathogenesis of AMD via triggering endothelial activation and inflammatory response in choroid, improving microcirculation, and reducing lipid deposition so as to inhibit the development of AMD-like lesions. Our study helps to provide a new therapeutic approach for the clinical treatment of AMD.
Animals ; Apolipoproteins E ; genetics ; metabolism ; Bruch Membrane ; metabolism ; ultrastructure ; Cholesterol ; blood ; Choroid ; metabolism ; ultrastructure ; DNA-Binding Proteins ; genetics ; metabolism ; Intercellular Adhesion Molecule-1 ; metabolism ; Macular Degeneration ; blood ; genetics ; metabolism ; Male ; Mice ; Mice, Knockout ; Microscopy, Electron, Transmission ; Microscopy, Fluorescence ; Retinal Pigment Epithelium ; metabolism ; ultrastructure

PURPOSE: To analyze the structural changes in the beta-zone of peripapillary atrophy (PPA-beta) using cross-sectional image of the optic disc head from spectral-domain optical coherence tomography (SD-OCT) according to the optic disc shape. METHODS: One hundred thirty-seven eyes in 137 patients with glaucoma having PPA-beta and 31 normal eyes (control group) were evaluated retrospectively. Cross-sectional images of the optic disc were taken using the Cirrus HD-OCT. We classified optic disc patterns into normal, focal, myopic, generalized enlargement and senile sclerotic appearance types and analyzed the shape of Bruch's membrane (BM), composition of retinal layer and retinal slope according to the optic disc shape. RESULTS: Among the 137 eyes with glaucoma, 54 eyes were focal disc type, 34 eyes were myopic disc type, 28 eyes were generalized enlargement disc type and 21 eyes were senile sclerotic disc type. The myopic disc group showed a noticeable difference compared to the other groups in terms of a higher percentage of BM defect type, the lowest retinal slope (70.6 +/- 12.0degrees) and the earlier termination of retinal layers. The generalized enlargement disc group showed the highest percentage of curved BM type. Retinal slope angle increased with age and decreased with axial length. CONCLUSIONS: In the beta-zone of peripapillary atrophy, there were several differences in the shape of Bruch's membrane, composition of retinal layers and the retinal slope according to the optic disc shape.
Atrophy* ; Bruch Membrane ; Glaucoma ; Head ; Humans ; Retinaldehyde ; Retrospective Studies ; Tomography, Optical Coherence

OBJECTIVE: To investigate and compare the growth of human fetal retinal pigment epithelial (RPE) cells seeded onto electrospun polyamide nanofibers (EPN) or etched pore polyester (EPP), and, further, to explore their possible use as prosthetic Bruch's membrane. METHODS: Human fetal RPE cells were planted onto the EPN, EPP and plastic (control) substrates in Transwells. The cultures were assessed with respect to cell attachment at 2, 4, 8 hours and proliferation at 1, 4, 8 days after seeding. Growth and morphology of the cells were monitored under the phase contrast microscope, and the phenotype was identified by immunofluorescence staining with antibodies against tight junction protein ZO-1. Strips of single EPP coated with nothing or EPP coated with EPN was differently implanted into the subretinal space of two P21 RCS rats for two weeks and the histologic slides of the retina were assessed. RESULTS: Cultured human fetal RPE cells were attached to either EPN or EPP substrates (with seeding on plastic substrate as control). After 8 h, the numbers of adherent cells in the EPN, EPP and control groups were 1.23*10(5)/cm(2), 1.70*10(5)/cm(2), and 1.64*10(5)/cm(2), respectively. The number of RPE cells attached to EPN was obviously less than that to both EPP and control (P<0.05). On the first day, the proliferation of cells on EPN was less than that of EPP and control (P<0.05); but by the 8th day in culture, the proliferation of cells on EPN had increased and was higher than proliferation on both EPP and control (P<0.05). All of the RPE cells cultured on EPN and EPP substrates were in monolayer, and the EPN-attached cells resembled the inner collagenous layer of Bruch's membrane. Immunofluorescence staining showed that the RPE cells cultured on EPN and EPP substrates adopted a higher expression of ZO-1 than that on the plastic control substrate. Subretinal implantation of either EPP alone or EPP as a carrier for free EPN for 2 weeks in P21RCS rats resulted in an expected encapsulation and loss of photoreceptor layer. No toxicity or other adverse reaction was observed in the vicinity of the transplant. CONCLUSION EPN and EPP could maintain human fetal RPE cell attachment and proliferation. Both EPN and EPP appeared to be grossly tolerance and biocompatible with subretinal implantation. EPN represents an intriguing prospect for prosthetic Bruch's membrane replacement because of its similarity in structure to native Bruch's membrane.
Animals ; Biocompatible Materials ; chemistry ; Bruch Membrane ; Cell Proliferation ; Cells, Cultured ; Fetus ; Humans ; Membranes, Artificial ; Nanofibers ; chemistry ; Polyesters ; chemistry ; Porosity ; Rats ; Retinal Pigment Epithelium ; cytology ; growth & development ; Tissue Engineering

PURPOSE: To characterize the features of peripapillary atrophy (PPA), as imaged by spectral-domain optical coherence tomography (SD-OCT). METHODS: SD-OCT imaging of the optic disc was performed on healthy eyes, eyes suspected of having glaucoma, and eyes diagnosed with glaucoma. From the peripheral beta-zone, the retinal nerve fiber layer (RNFL), the junction of the inner and outer segments (IS/OS) of the photoreceptor layer, and the Bruch's membrane/retinal pigment epithelium complex layer (BRL) were visualized. RESULTS: Nineteen consecutive eyes of 10 subjects were imaged. The RNFL was observed in the PPA beta-zone of all eyes, and no eye showed an IS/OS complex in the beta-zone. The BRL was absent in the beta-zone of two eyes. The BRL was incomplete or showed posterior bowing in the beta-zone of five eyes. CONCLUSIONS: The common findings in the PPA beta-zone were that the RNFL was present, but the photoreceptor layer was absent. Presence of the BRL was variable in the beta-zone areas.
Adult ; Aged ; Bruch Membrane/pathology ; Female ; Glaucoma/*complications ; Humans ; Male ; Middle Aged ; Nerve Fibers/pathology ; Optic Atrophy/*diagnosis/*etiology ; Optic Disk/*pathology ; Photoreceptor Cells, Vertebrate/pathology ; Retina/pathology ; Retinal Pigment Epithelium/pathology ; Tomography, Optical Coherence/*methods

PURPOSE: To evaluate the effect of adding exogenous extracellular matrix (ECM) proteins on the reattachment of retinal pigment epithelium (RPE) to the damaged surface of Bruch's membrane (BM). METHODS: Porcine BM explants were divided into six groups: BMs with an intact basal lamina (bl-BM) and five damaged BMs (d-BM: bare & four ECM-coated). The d-BM was coated with ECM proteins (either fibronectin, laminin, collagen IV, or all). Primary RPE sheets were plated and cultured for each group of BM explants. The attached live cells were counted and examined with a scanning electron microscope after three days, as well as at 1, 2 and 4 weeks. RESULTS: The RPE reattachment rate was highest in bl-BM and lowest in uncoated d-BM. ECM-coated groups showed a lower reattachment rate than bl-BM, but when compared with the uncoated group, the reattachment rate was significantly increased (p<0.05). ECM-exposure time did not influence the reattachment rate of any of the groups. RPE cells plated on bl-BMs and ECM-coated d-BMs attached and proliferated well and achieved confluence over time. Even though most cells were flat and large in shape, some cells revealed a good morphology with microvilli on their surface. On the other hand, only some of the RPE sheets plated on the uncoated d-BM attached loosely and most cells remained round and clumped. CONCLUSIONS: These results show that the addition of ECM proteins may increase the ability of RPE cells to reattach to the damaged BM surface, which would likely create a good morphology.
Basement Membrane ; Bruch Membrane ; Collagen ; Epithelial Cells* ; Extracellular Matrix Proteins* ; Extracellular Matrix* ; Fibronectins ; Hand ; Laminin ; Microvilli ; Retinal Pigment Epithelium ; Retinaldehyde*