PURPOSE: To assess whether the asymmetry in the peripapillary retinal nerve fiber layer (pRNFL) thickness between superior and inferior hemispheres on optical coherence tomography (OCT) is useful for early detection of glaucoma. MATERIALS AND METHODS: The patient population consisted of Training set (a total of 60 subjects with early glaucoma and 59 normal subjects) and Validation set (30 subjects with early glaucoma and 30 normal subjects). Two kinds of ratios were employed to measure the asymmetry between the superior and inferior pRNFL thickness using OCT. One was the ratio of the superior to inferior peak thicknesses (peak pRNFL thickness ratio; PTR), and the other was the ratio of the superior to inferior average thickness (average pRNFL thickness ratio; ATR). The diagnostic abilities of the PTR and ATR were compared to the color code classification in OCT. Using the optimal cut-off values of the PTR and ATR obtained from the Training set, the two ratios were independently validated for diagnostic capability. RESULTS: For the Training set, the sensitivities/specificities of the PTR, ATR, quadrants color code classification, and clock-hour color code classification were 81.7%/93.2%, 71.7%/74.6%, 75.0%/93.2%, and 75.0%/79.7%, respectively. The PTR showed a better diagnostic performance for early glaucoma detection than the ATR and the clock-hour color code classification in terms of areas under the receiver operating characteristic curves (AUCs) (0.898, 0.765, and 0.773, respectively). For the Validation set, the PTR also showed the best sensitivity and AUC. CONCLUSION: The PTR is a simple method with considerable diagnostic ability for early glaucoma detection. It can, therefore, be widely used as a new screening method for early glaucoma.
Area Under Curve ; Color ; Early Diagnosis ; Female ; Glaucoma/diagnosis ; Humans ; Male ; Mass Screening/methods ; Middle Aged ; Nerve Fibers/pathology ; ROC Curve ; Reproducibility of Results ; Retina/pathology ; Retinal Ganglion Cells ; Sensitivity and Specificity

Objective To assess the in vivo dynamic blood flow features of posterior optic nerve head (ONH) in rat model of nonarteritic anterior ischemic optic neuropathy (rNAION). Methods rNAION was established with Rose Bengal and argon green laser in Sprague-Dawley rats. Fundus photography and fundus fluorescein angiography (FFA) were performed to assess the dynamic changes of optic disc in morphology in 90 days and in blood perfusion in 3 hours after the induction of disease. Histological examinations were performed to evaluate the success of modeling. The dynamic blood flow kinetics of posterior ONH in rNAION were measured by Laser Doppler Flowmetry (LDF) on the day 3, 7, 14, 21, and 40 after the disease induction. One-way ANOVA, Student's t-test and Bonferroni adjustment were used for multiple comparisons of kinetic measurements of blood flow. Results Optic disc edema and subsequent resolution associated with the development of optic disc pallor were observed in rNAION. FFA showed that the optic disc was hypofluorescence in the early phase and hyperfluorescence in the late phase. Histological studies suggested edema and loosened tissues of ONH, loss of retinal ganglion cells (RGCs), optic nerve substance and gliosis. Compared to the naive rats, the blood flow kinetics of posterior ONH in rNAION significant reduced at each time point after modeling (F=175.06, P<0.0001). The reductions were specifically remarkable in 14 days after the disease induction (All P<0.01). Conclusions Continuous blood perfusion reduction was found in rNAION, with significant alteration in 14 days after disease induction. Our results provided important information for understanding the hemodynamic changes in rNAION.
Animals ; Disease Models, Animal ; Fluorescein Angiography ; Hemodynamics ; physiology ; Humans ; Male ; Optic Disk ; pathology ; physiopathology ; Optic Neuropathy, Ischemic ; pathology ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Retinal Ganglion Cells ; physiology

BACKGROUNDMorphological changes of the vasculature system in patients with myopia have been observed by Doppler ultrasound and fundus fluorescein angiography (FFA); however, these studies have limitations. Doppler ultrasound provides low-resolution images which are mainly obtained from visualized large vessels, and FFA is an invasive examination. Optic coherence tomography (OCT) angiography is a noninvasive, high-resolution measurement for vascular density. The purpose of this study was to investigate the change of vascular density in myopic eyes using OCT angiography.

METHODSThis cross-sectional study includes a total of 91 eyes from 47 participants including control, moderate, and high myopia that were evaluated by OCT angiography. Patients with myopia were recruited from the Refractive Department, Shenzhen Aier Eye Hospital, from August 5, 2015 to April 1, 2016. Emmetropic eyes were from healthy volunteers. The vascular density at macula and optic disc regions, ganglion cell complex (GCC) thickness, and retinal nerve fiber layer (RNFL) thickness were measured. Their relationships with axial length (AL) and refractive error were analyzed. One-way analysis of variance (ANOVA), Pearson's correlation, and generalized estimating equation were used for statistical analysis.

RESULTSBoth superficial and deep macular vascular density were highest in control (25.64% ± 3.76% and 37.12% ± 3.66%, respectively), then in moderate myopia (21.15% ± 5.33% and 35.35% ± 5.50%, respectively), and lowest in high myopia group (19.64% ± 3.87% and 32.81% ± 6.29%, respectively) (F = 13.74 and 4.57, respectively; both P < 0.001). Both superficial (β = -0.850 and 0.460, respectively) and deep (β = -0.766 and 0.396, respectively) macular vascular density were associated with AL and spherical equivalent (all P < 0.001). Superficial macular vascular density was associated with GCC thickness (β = 0.244, P = 0.040), independent of spherical equivalent. The vascular density in optic disc region had no difference among the three groups, and it was not associated with AL, spherical equivalent, or RNFL thickness.

CONCLUSIONOur results suggested that with the increase of myopia, the vascular density decreased in macular region, but not in optic disc region.

Adult ; Cross-Sectional Studies ; Eye ; blood supply ; Female ; Fluorescein Angiography ; Humans ; Macula Lutea ; pathology ; physiopathology ; Male ; Middle Aged ; Myopia ; pathology ; physiopathology ; Optic Disk ; pathology ; physiopathology ; Prospective Studies ; Retina ; pathology ; physiopathology ; Retinal Ganglion Cells ; pathology ; Tomography, Optical Coherence ; Young Adult

BACKGROUNDCollapsin response mediator protein-2 (CRMP2) has been shown to be involved in ischemia/hypoxia (IH) injury. We determined whether CRMP2 modulates ischemic injury in the retinal of Ocular ischemic syndrome (OIS). This study was to explore the molecular mechanisms underlying OIS in a novel mice model.

METHODSExperiments were performed on adult male C57/BL6 mice that received bilateral internal carotid arteries ligation for 1, 2, or 4 weeks. The mice received injection of calpeptin group before occlusion for 4 weeks or not. The expression of CRMP2 in the retinal was examined by western blotting (WB) analysis and immunohistochemical analysis (IHC). The effects of ischemic injury on retinal were evaluated by fundus examination, fundus fluorescein angiography, electroretinogram, cell counting of retinal ganglion cell (RGC), and measurement of the thickness of the retina.

RESULTSThe veins dilated after chronic ischemia. In the electroretinography, the amplitudes of a- and b-waves kept diminishing in an ischemia time-dependent manner. Moreover, the tail vein-retinal circulation time prolonged in the 1- and 2-week group. In comparison, thickness of the retina decreased gradually with the ischemia time elapsed. WB analysis showed the CRMP2 and p-CRMP2 levels decreased in the 2- and 4-week groups. The results of IHC analysis were compatible with our results of WB. The loss of RGCs, decrease of the total reaction time and reduction of CRMP2 was alleviated by intravitreal injection of calpeptin.

CONCLUSIONSThese results revealed that bilateral ligation of the internal carotid artery causes retinal ischemia in mice. Moreover, CRMP2 might play a pivotal role during the ischemic injury in the retina and inhibit the cleavage of CRMP2 can ameliorate the IH injury.

Animals ; Disease Models, Animal ; Electroretinography ; Intercellular Signaling Peptides and Proteins ; genetics ; metabolism ; Ischemia ; genetics ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins ; genetics ; metabolism ; Retinal Diseases ; genetics ; metabolism ; pathology ; Retinal Ganglion Cells ; metabolism ; pathology

The purpose of this study was to investigate the effect of inhibition of calpain on retinal ganglion cell-5 (RGC-5) necroptosis following oxygen glucose deprivation (OGD). RGC-5 cells were cultured in Dulbecco's-modified essential medium and necroptosis was induced by 8-h OGD. PI staining and flow cytometry were performed to detect RGC-5 necrosis. The calpain expression was detected by Western blotting and immunofluorescence staining. The calpain activity was tested by activity detection kit. Flow cytometry was used to detect the effect of calpain on RGC-5 necroptosis following OGD with or without N-acetyl-leucyl-leucyl-norleucinal (ALLN) pre-treatment. Western blot was used to detect the protein level of truncated apoptosis inducing factor (tAIF) in RGC-5 cells following OGD. The results showed that there was an up-regulation of the calpain expression and activity following OGD. Upon adding ALLN, the calpain activity was inhibited and tAIF was reduced following OGD along with the decreased number of RGC-5 necroptosis. In conclusion, calpain was involved in OGD-induced RGC-5 necroptosis with the increased expression of its downstream molecule tAIF.
Animals ; Apoptosis Inducing Factor ; biosynthesis ; genetics ; Calpain ; biosynthesis ; genetics ; Gene Expression Regulation ; drug effects ; Glucose ; metabolism ; Humans ; Leupeptins ; administration & dosage ; Mice ; Oxygen ; metabolism ; Retinal Ganglion Cells ; metabolism ; pathology ; Retinal Necrosis Syndrome, Acute ; genetics ; pathology

Diabetic Retinopathy ; complications ; epidemiology ; physiopathology ; Humans ; Neurodegenerative Diseases ; epidemiology ; etiology ; physiopathology ; Retinal Ganglion Cells ; pathology ; Risk Factors

PURPOSE: To investigate the use of ganglion cell inner plexiform layer (GC-IPL) thickness, as measured by spectral domain optical coherence tomography, to detect central visual field (VF) progression. METHODS: This study included 384 eyes from 384 patients (219 preperimetric and 165 perimetric glaucomatous eyes; average follow-up, 4.3 years). Photographic assessment of retinal nerve fiber layer (RNFL) and serial VF analysis were performed to detect glaucoma progression in the central (within 10°) area. Study inclusion required at least five serial spectral domain optical coherence tomography exams at different visits. The long-term test-retest variability of average GC-IPL thicknesses was calculated in 110 stable preperimetric glaucomatous eyes. The sensitivity and specificity of GC-IPL measurements for the detection of central VF progression were calculated in an event-based analysis using the calculated variability as a cut-off and were compared with those of central RNFL photographic assessment. RESULTS: The intersession test-retest variability, defined as the 95% confidence interval, was 1.76 µm for average GC-IPL thickness. The sensitivity and specificity of the average GC-IPL thickness for detecting central VF progression were 60.7% and 78.9%, respectively. Among six sectors, the inferonasal GC-IPL sector showed the highest sensitivity (53.6%). The sensitivity of the ≥1 sector GC-IPL to detect central VF progression was significantly higher than that of central RNFL photographic progression (p = 0.013). Other GC-IPL parameters showed comparable sensitivity and specificity to detect central VF progression compared with RNFL photographic progression. CONCLUSIONS: Serial GC-IPL measurements show comparable performance in the detection of central glaucomatous VF progression to RNFL photographic assessment.
Disease Progression ; Female ; Follow-Up Studies ; Glaucoma/*diagnosis/physiopathology ; Humans ; *Intraocular Pressure ; Macula Lutea/*diagnostic imaging ; Male ; Middle Aged ; ROC Curve ; Retinal Ganglion Cells/*pathology ; Retrospective Studies ; Time Factors ; Tomography, Optical Coherence/*methods ; *Visual Fields

PURPOSE: To investigate and compare the progression of medically treated primary open angle glaucoma according to the baseline intraocular pressure (IOP). METHODS: This study included a total of 345 eyes from 345 patients (mean follow-up period, 4.5 years). Eyes were classified into either conventional normal tension glaucoma (cNTG, < or =21 mmHg) or conventional high-tension glaucoma (cHTG, >21 mmHg) groups according to the conventional cut-off value of the IOP. Additionally, the median IOP (15 mmHg) was used to create two other groups (median NTG [mNTG] < or =15 mmHg and median HTG [mHTG] >15 mmHg). Using these values, 306, 39, 153, and 192 eyes were assigned to the cNTG, cHTG, mNTG, and mHTG groups, respectively. Glaucoma progression was determined either by optic disc/retinal nerve fiber layer photographs or serial visual field data. RESULTS: Mean reduction of IOP after medical treatment and of central corneal thickness was lower in the cNTG group, while the prevalence of disc hemorrhage and baseline visual field mean deviation did not differ between the cNTG and cHTG groups. A mean reduction in the IOP was observed after medical treatment, and central corneal thickness was lower in the mNTG group; disc hemorrhage was more frequent in the mNTG than in the mHTG group. Among the 345 analyzed eyes, 100 (29%) showed progression during the follow-up period. In the cHTG group, a higher baseline IOP (hazard ratio, 1.147; p = 0.024) was associated with glaucoma progression. Disc hemorrhage (hazard ratio, 15.533; p < 0.001) was also strongly associated with progression in the mNTG group. CONCLUSIONS: Baseline IOP was a significant risk factor for glaucoma progression in cHTG patients (10% of our total participants), while disc hemorrhage showed the strongest association with progression in the mNTG group, indicating that a cut-off value other than the conventional 21 mmHg is required to define true low-tension glaucoma in populations where NTG predominates among all glaucoma patients.
Aged ; Disease Progression ; Female ; Glaucoma, Open-Angle/*diagnosis ; Gonioscopy ; Humans ; Intraocular Pressure ; Low Tension Glaucoma/*diagnosis ; Male ; Middle Aged ; Nerve Fibers/pathology ; Optic Disk/pathology ; Optic Nerve Diseases/*diagnosis ; Photography/standards ; Retinal Ganglion Cells/pathology ; Retrospective Studies ; Tomography, Optical Coherence ; Tonometry, Ocular ; Vision Disorders/diagnosis ; Visual Field Tests/standards ; Visual Fields

PURPOSE: Though there are many reports regarding the structure-function relationship in glaucoma, they are too complicated to apply to the routine clinical setting. The aim of this study was to investigate the direct relationship between peripapillary retinal nerve fiber layer (RNFL) thickness measured by optical coherence tomography (OCT) and visual field (VF) severity indices computed by standard automated perimetry. METHODS: This cross-sectional comparative study included 104 glaucomatous patients and 59 healthy subjects. Peripapillary RNFL thickness was measured by spectral domain (SD) and time domain (TD) OCTs. Four glaucoma VF severity indices, including mean deviation (MD), pattern standard deviation (PSD), Collaborative Initial Glaucoma Treatment Study (CIGTS) VF score, and Advanced Glaucoma Intervention Study (AGIS) VF score, were calculated using standard automated perimetry. The Pearson's correlation coefficients (r) between the average and quadrants of peripapillary RNFL thicknesses and the four VF severity indices were calculated. RESULTS: In glaucomatous eyes, the r value between the average RNFL thickness measured by SD OCT and each VF severity index were 0.562, -0.514, -0.577, and -0.567 for the MD, PSD, CIGTS VF score, and AGIS VF score, respectively (all p < 0.001). Among each quadrant, the inferior RNFL thickness showed the largest r value; 0.587, -0.552, -0.613, and -0.598 for the MD, PSD, CIGTS VF score, and AGIS VF score, respectively (all p < 0.001). Measurements by TD OCT showed similar strengths of association with SD OCT. CONCLUSIONS: Moderate correlation was identified between peripapillary RNFL thicknesses measured by SD/TD OCT and glaucoma VF severity indices. Among each quadrant, the inferior RNFL thickness showed the greatest association with glaucoma VF severity indices. There was no significant difference according to the type of VF severity index or the type of OCTs.
Adult ; Aged ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Nerve Fibers/*pathology ; Optic Nerve/*pathology ; Optic Nerve Diseases/*diagnostic imaging/physiopathology ; Retinal Ganglion Cells/*pathology ; Severity of Illness Index ; Tomography, Optical Coherence/*methods ; Visual Field Tests/methods ; Visual Fields/*physiology ; Young Adult

PURPOSE: To investigate the differences in retinal nerve fiber layer (RNFL) change and optic nerve head parameters between non-arteritic anterior ischemic optic neuropathy (NAION) and open angle glaucoma (OAG) with altitudinal visual field defect. METHODS: Seventeen NAION patients and 26 OAG patients were enrolled prospectively. The standard visual field indices (mean deviation, pattern standard deviation) were obtained from the Humphrey visual field test and differences between the two groups were analyzed. Cirrus HD-OCT parameters were used, including optic disc head analysis, average RNFL thickness, and RNFL thickness of each quadrant. RESULTS: The mean deviation and pattern standard deviation were not significantly different between the groups. In the affected eye, although the disc area was similar between the two groups (2.00 +/- 0.32 and 1.99 +/- 0.33 mm2, p = 0.586), the rim area of the OAG group was smaller than that of the NAION group (1.26 +/- 0.56 and 0.61 +/- 0.15 mm2, respectively, p < 0.001). RNFL asymmetry was not different between the two groups (p = 0.265), but the inferior RNFL thickness of both the affected and unaffected eyes were less in the OAG group than in the NAION group. In the analysis of optic disc morphology, both affected and unaffected eyes showed significant differences between two groups. CONCLUSIONS: To differentiate NAION from OAG in eyes with altitudinal visual field defects, optic disc head analysis of not only the affected eye, but also the unaffected eye, by using spectral domain optical coherence tomography may be helpful.
Aged ; Arteritis/diagnosis ; Diagnosis, Differential ; Female ; Glaucoma, Open-Angle/*diagnosis ; Humans ; Male ; Middle Aged ; Nerve Fibers/*pathology ; Optic Disk/*pathology ; Optic Neuropathy, Ischemic/*diagnosis ; Prospective Studies ; Retinal Ganglion Cells/*pathology ; Tomography, Optical Coherence ; Vision Disorders/*diagnosis ; Visual Field Tests ; *Visual Fields