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1.  Choroidal Thickness Measured by Spectral Domain Optical Coherence Tomography: Factors Affecting Thickness in Glaucoma Patients 
Ophthalmology  2011;118(8):1571-1579.
To measure choroidal thickness and to determine parameters associated with it.
Cross-sectional study.
Seventy-four glaucoma patients and glaucoma suspects.
Spectral domain optical coherence tomography (SDOCT) scans were obtained to estimate average choroidal thickness in a group of glaucoma suspects and glaucoma patients. Average thickness was calculated from enhanced depth SDOCT images and manually analyzed with Image J software. Open angle glaucoma, open angle glaucoma suspect, primary angle closure glaucoma, primary angle closure, and primary angle closure suspect were defined by published criteria. Glaucoma suspects had normal visual fields bilaterally. Glaucoma was defined by specific criteria for optic disc damage and visual field loss in at least one eye. The most affected eye was analyzed for comparisons across individuals, while right/left and upper half/lower half comparisons were made to compare thickness against degree of visual field damage.
Main Outcome Measured
Average macular and peripapillary choroidal thickness measured using SDOCT.
The choroidal-scleral interface (CSI) was visualized in 86% and 96% of the macular and peripapillary scans, respectively. In multivariable linear regression analysis, the macular choroid was significantly thinner in association with 4 features: longer eyes (22 µm per mm longer [95% confidence Interval (CI): −33, −11]), older individuals (31 µm thinner per decade older [95% CI: −44 −17]), lower diastolic ocular perfusion pressure (26 µm thinner per 10 mmHg lower [95% CI: 8, 44]), and thicker central corneas (6 µm per 10 µm thicker cornea [95% CI: −10, 0]). The choroid was not significantly thinner in glaucoma patients than in suspects (14 µm [95% CI: −54, 26], p=0.5). Peripapillary choroidal thickness was not significantly different between glaucomaand suspect patients. Thickness was not associated with damage severity as estimated by visual field mean deviation or nerve fiber layer thickness, including comparisons of right to left eye or upper to lower values.
Age, axial length, central corneal thickness, and diastolic ocular perfusion pressure are significantly associated with choroidal thickness in glaucoma suspects and glaucoma patients. Degree of glaucoma damage was not consistently associated with choroidal thickness.
PMCID: PMC3139809  PMID: 21492939
2.  Analysis of Normal Peripapillary Choroidal Thickness via Spectral Domain Optical Coherence Tomography 
Ophthalmology  2011;118(10):2001-2007.
To analyze the normal peripapillary choroidal thickness utilizing a commercial spectral domain optical coherence tomography (OCT) device and determine the inter-grader reproducibility of this method.
Retrospective, non-comparative, non-interventional case series.
Thirty-six eyes of 36 normal patients seen at the New England Eye Center between April and September 2010.
All patients underwent high-definition scanning with the Cirrus HD-OCT. Two raster scans were obtained per eye, a horizontal and a vertical scan, both of which were centered at the optic nerve. Two independent graders individually measured the choroidal thickness. Choroidal thickness was measured from the posterior edge of the retinal pigment epithelium to the choroid-scleral junction at 500 μm intervals away from the optic nerve in the superior, inferior, nasal and temporal quadrants. Statistical analysis was conducted to compare mean choroidal thicknesses. Inter-grader reproducibility was assessed by intraclass correlation coefficient and Pearson’s correlation coefficient. Average choroidal thickness in each quadrant was compared to retinal nerve fiber layer (RNFL) thickness in their respective quadrants.
Peripapillary choroidal thickness, intraclass coefficient, Pearson’s correlation coefficient.
The peripapillary choroid in the inferior quadrant was significantly thinner compared to all other quadrants (p< 0.001). None of the other quadrants were significantly different from each other in terms of thickness. The inferior peripapillary choroid was significantly thinner compared to all other quadrants at all distances measured away from the optic nerve (p< 0.001). Generally, the peripapillary choroid increases in thickness the farther it was away from the optic nerve and eventually approaching a plateau. Intraclass correlation coefficient ranged from 0.62 to 0.93 and Pearson’s correlation coefficient ranged from 0.74 to 0.95 (p< 0.001). Neither RNFL thickness nor average age was significantly correlated with average choroidal thickness.
Manual segmentation of the peripapillary choroidal thickness is reproducible between graders suggesting that this method is accurate. The inferior peripapillary choroid was significantly thinner than all other quadrants (p< 0.001).
PMCID: PMC3184379  PMID: 21703691
3.  Peripapillary choroidal thickness in healthy Chinese subjects 
BMC Ophthalmology  2013;13:23.
To evaluate the peripapillary choroidal thickness of a healthy Chinese population, and to determine its influencing factors.
A total of 76 healthy volunteers (76 eyes) without ophthalmic or systemic symptoms were enrolled. Choroidal scans (360-degree 3.4 mm diameter peripapillary circle scans) were obtained for all eyes using enhanced depth imaging spectral-domain optical coherence tomography. Choroid thickness was measured at the temporal, superotemporal, superior, superonasal, nasal, inferonasal, inferior, and inferotemporal segments.
The average peripapillary choroidal thicknesses were 165.03 ± 40.37 μm. Inferonasal, inferior, and inferotemporal thicknesses were significantly thinner than temporal, superotemporal, superior, superonasal, nasal thicknesses (p < 0.05). No statistically significant difference was found among inferonasal, inferior, and inferotemporal thicknesses. The average peripapillary choroidal thickness decreased linearly with age (β = −1.33, 95% CI −1.98, -0.68, P < 0.001). No correlation was noted between average choroidal thickness and other factors (gender, refractive error, axial length, average retinal nerve fiber layer thickness, intraocular pressure, diastolic blood pressure, systolic blood pressure, mean blood pressure, diastolic ocular perfusion pressure, systolic ocular perfusion pressure, and mean ocular perfusion pressure).
The inferonasal, inferior, inferotemporal peripapillary choroidal thicknesses were significantly thinner than temporal, superotemporal, superior, superonasal, and nasal thicknesses. A thinner peripapillary choroid is associated with increasing age.
PMCID: PMC3685566  PMID: 23758729
Peripapillary choroidal thickness; Enhanced depth imaging optical coherence tomography; Healthy Chinese subjects
4.  Peripapillary and Macular Choroidal Thickness in Glaucoma 
To compare choroidal thickness (CT) between individuals with and without glaucomatous damage and to explore the association of peripapillary and submacular CT with glaucoma severity using spectral domain optical coherence tomography (SD-OCT).
Ninety-one eyes of 20 normal subjects and 43 glaucoma patients from the UCLA SD-OCT Imaging Study were enrolled. Imaging was performed using Cirrus HD-OCT. Choroidal thickness was measured at four predetermined points in the macular and peripapillary regions, and compared between glaucoma and control groups before and after adjusting for potential confounding variables.
The average (± standard deviation) mean deviation (MD) on visual fields was −0.3 (±2.0) dB in controls and −3.5 (±3.5) dB in glaucoma patients. Age, axial length and their interaction were the most significant factors affecting CT on multivariate analysis. Adjusted average CT (corrected for age, axial length, their interaction, gender and lens status) however, was not different between glaucoma patients and the control group (P=0.083) except in the temporal parafoveal region (P=0.037); nor was choroidal thickness related to glaucoma severity (r=−0.187, P=0.176 for correlation with MD, r=−0.151, P=0.275 for correlation with average nerve fiber layer thickness).
Choroidal thickness of the macular and peripapillary regions is not decreased in glaucoma. Anatomical measurements with SD-OCT do not support the possible influence of the choroid on the pathophysiology of glaucoma.
PMCID: PMC4181196  PMID: 25279115
Glaucoma; Spectral-Domain Optical Coherence Tomography; Choroidal Thickness; Peripapillary; Macula
5.  Lack of Association between Glaucoma and Macular Choroidal Thickness Measured with Enhanced Depth-Imaging Optical Coherence Tomography 
Enhanced depth-imaging optical coherence tomography was used to measure choroidal thickness in subjects with normal vision, primary-open angle glaucoma, and normal tension glaucoma. No difference was found in choroidal thickness, suggesting a lack of relationship between choroidal thickness and glaucoma.
To compare choroidal thickness measurements among normal eyes, eyes with normal tension glaucoma (NTG), and those with primary open-angle glaucoma (POAG), and to correlate choroidal thickness with demographic and clinical ocular parameters.
Choroidal thickness was measured with enhanced depth-imaging (EDI) optical coherence tomography (OCT) in one eye of 38 normal, 20 NTG, and 56 POAG subjects and compared among groups. The mean age was 69.3 ± 13.6 years (60.1 ± 13.4 years for normal subjects and 73.8 ± 11.3 years for glaucoma subjects; P < 0.001). Measurements were made at the fovea and in the temporal and nasal choroid every 0.5 mm up to 3 mm away from the fovea. Univariate and multivariate linear regression analyses were performed to assess the association between choroidal thickness and demographic and ocular parameters.
There were no differences in foveal, temporal, or nasal choroidal thickness between normal, NTG, and POAG subjects (all P > 0.05) after adjusting for age, axial length, and intraocular pressure. Similarly, glaucoma severity groups did not differ from each other in all choroidal thickness measurements (all P > 0.05). Age (β = −1.78; P < 0.001) was the most significant factor associated with subfoveal choroidal thickness in the entire group, followed by axial length (β = −11.8; P = 0.002).
Choroidal thickness does not differ among normal, NTG, and POAG subjects, suggesting a lack of relationship between choroidal thickness and glaucoma based on EDI OCT measurements.
PMCID: PMC3109036  PMID: 21357398
6.  Retinal nerve fiber layer thickness in glaucomatous Nepalese eyes and its relation with visual field sensitivity 
Journal of Optometry  2014;7(4):217-224.
To evaluate peripapillary retinal nerve fiber layer (RNFL) thickness in glaucomatous Nepalese eyes using spectral domain optical coherence tomography (SD-OCT) and study its relationship with visual field sensitivity.
A total of 120 eyes comprising primary open angle glaucoma (POAG), glaucoma suspects (GS), normal tension glaucoma (NTG) and healthy subjects (n = 30 cases in each group) underwent a complete ophthalmic examination, including optic nerve head (ONH) evaluation and standard automated perimetry (SAP). RNFL thickness measurements around the optic disk were taken with circular spectral domain optical coherence tomography (SD-OCT) scans. Analysis of variance (ANOVA) was used for comparison of RNFL parameters among various study groups. The relationship of RNFL parameters with visual field (VF) global indices was evaluated with regression analysis.
The mean pRNFL thickness was significantly less in the POAG (64.30 ± 14.45 μm, p < 0.01), NTG (85.43 ± 9.79 μm, p < 0.001) and GS (102.0 ± 9.37 μm, p < 0.001) groups than in the healthy group (109.8 ± 8.32 μm). The RNFL was significantly thinner across all quadrants in all study group pairs (p < 0.05) except for normal vs. GS (only superior and inferior quadrant, significant). Linear regression plots with RNFL thickness as a predictor of MD and LV demonstrated a strong and statistically significant degree of determination in the POAG group (R2 = 0.203 and 0.175, p = 0.013 and 0.021).
The RNFL thickness measurements with SD-OCT are lower in glaucomatous eyes as compared to age-matched GS and normal eyes in the Nepalese population. A high resolution SD-OCT could aid significantly in the early diagnosis of glaucoma in Nepal.
PMCID: PMC4213835  PMID: 25323643
Glaucoma; Nerve fiber layer; Optical coherence tomography; Visual field; Primary open angle glaucoma; Glaucoma; Capa de fibras nerviosas; Tomografía de coherencia óptica; Campo visual; Glaucoma primario de ángulo abierto
7.  Relationship between the Lamina Cribrosa, Outer Retina, and Choroidal Thickness as Assessed Using Spectral Domain Optical Coherence Tomography 
To evaluate the characteristics and relationship between peripapillary choroidal thickness (pCT), lamina cribrosa thickness (LCT), and peripapillary outer retinal layer thickness (pORT) as determined using spectral domain optical coherence tomography (SD-OCT) enhanced depth imaging (EDI).
In total, 255 participants were included (87 healthy subjects, 87 glaucoma suspects (GS), and 81 glaucoma cases). The pORT, defined as the thickness between the posterior outer plexiform layer and the retinal pigment epithelium (RPE) interface, and the pCT, between the outer margin of the RPE and the choroidal-scleral interface, were manually measured using EDI scanning of the circumpapillary retinal nerve fiber layer (RNFL). LCT was determined by EDI scanning of the optic nerve head (ONH). Baseline characteristics, including axial length (AXL) and the SD-OCT measurements of the participants, were compared among the three groups. The correlation between putative factors and pCT was determined using univariate and multivariate linear regression analyses.
In all three groups, both pORT and pCT were thinnest in the inferior area among the four quadrants. In the healthy group, the mean peripapillary RNFL, pORT, and LCT were significantly greater in comparison with those of the GS and glaucoma groups (p < 0.001, p < 0.038, and p < 0.001, respectively). The pCT demonstrated no significant differences among the three groups (p = 0.083). Only age and AXL were associated with pCT by multivariate analysis.
The pCT is substantially thinner in the inferior area of the ONH. In addition, the pCT demonstrates the strongest correlation with age and AXL, but was not associated with glaucoma or LCT.
PMCID: PMC4038729  PMID: 24882957
Choroidal thickness; Glaucoma; Lamina cribrosa thickness; Optical coherence tomography; Outer retinal thickness
8.  Comparison of Retinal Nerve Fiber Layer Measurements Using Time Domain and Spectral Domain Optical Coherent Tomography 
Ophthalmology  2009;116(7):1271-1277.
To determine the agreement between peripapillary retinal nerve fiber layer (RNFL) thickness measurements from Stratus time domain optical coherence tomography (OCT) and Cirrus spectral domain OCT (Carl Zeiss Meditec, Dublin, CA) in normal subjects and glaucoma patients.
Evaluation of diagnostic test or technology.
One hundred thirty eyes from 130 normal subjects and glaucoma patients were analyzed. The subjects were divided into Normal (n=29), Glaucoma Suspect (n=12), Mild Glaucoma (n=41), Moderate Glaucoma (n=18), and Severe Glaucoma (n=30) by visual field criteria.
Peripapillary RNFL thickness was measured with Stratus Fast RNFL and Cirrus 200 x 200 Optic Disc Scan on the same day in one eye of each subject to determine agreement. Two operators used the same instruments for all scans.
Main Outcome Measures
Student paired t-testing, Pearson’s correlation coefficient, and Bland-Altman analysis of RNFL thickness measurements.
The average age of the glaucoma group was significantly older at 68.3±12.3 years versus 55.7±12.1 years. The average RNFL thickness (mean ± SD, in μm) for each severity group with Stratus OCT was 99.4 ± 13.2, 94.5 ± 15.0, 79.0 ± 14.5, 62.7 ± 10.2, and 51.0 ± 8.9, corresponding to normal, suspects, mild, moderate, and severe subjects, respectively. For Cirrus OCT, the corresponding measurements were 92.0 ± 10.8, 88.1 ± 13.5, 73.3 ± 11.8, 60.9 ± 8.3, and 55.3 ± 6.6. All Stratus-Cirrus differences were statistically significant by paired t-testing (p < 0.001) except for the moderate group (p = 0.11). For average RNFL, there was a highly significant linear relationship between Stratus minus Cirrus difference and RNFL thickness as well (p < 0.001). Bland-Altman plots showed that the systematic difference of Stratus measurements are smaller than Cirrus at thinner RNFL values but larger at thicker RNFL measurements.
RNFL thickness measurements between Stratus OCT and Cirrus OCT cannot be directly compared. Clinicians should be aware that measurements are generally higher with Stratus than Cirrus except when the RNFL is very thin as in severe glaucoma. This difference must be taken into account if comparing measurements made with a Stratus instrument to those of a Cirrus instrument.
PMCID: PMC2713355  PMID: 19395086
9.  The Whole Macular Choroidal Thickness in Subjects with Primary Open Angle Glaucoma 
PLoS ONE  2014;9(10):e110265.
We investigated the whole macular choroidal thickness in subjects with glaucoma in order to evaluate the effects of glaucoma and glaucoma visual field damage on the choroidal thickness.
Subjects and Methods
We examined 40 primary open angle glaucoma patients with only superior visual field defects and 48 normal controls. The macular choroidal thickness was measured using swept-source optical coherence tomography according to the three-dimensional raster scan protocol (6×6 mm). We used the choroidal thickness within a 1.0-mm circle measured on ETDRS grids as the central sector and then used a 6×6 rectangular grid to divide the area into six sectors.
No significant differences were found in the choroidal thickness values between the glaucoma and normal subjects in any of the sectors after adjusting for the age and axial length (all P>0.4, ANCOVA). According to a stepwise analysis of the glaucoma subjects performed using the parameters of age, axial length, central corneal thickness and mean deviation (MD value) obtained by static perimetry, age was the most predictive and significant factor in all sectors (coefficient  = −3.091 to −4.091 and F value  = 15.629 to 22.245), followed by axial length (coefficient  = −10.428 to −23.458 and F value  = 2.454 to 6.369). The central corneal thickness and MD values were not significant predictive factors in any of the sectors. No significant predictive factors were found for the differences in the choroidal thickness values observed between the superior and inferior field sectors.
Neither the glaucoma-related visual field damage nor glaucoma itself have any apparent associations with the whole macular choroidal thickness.
Trial Registration
Japan Clinical Trials Register ( number, UMIN 000012527).
PMCID: PMC4211920  PMID: 25350379
10.  Clinicopathologic Correlation of Disc and Peripapillary Region Using SD-OCT 
To describe a technique for evaluating peripapillary and optic nerve head (ONH) anatomy using spectral domain optical coherence tomography (SD-OCT) raster scanning in humans and compare quantifiable parameters between diagnosis categories.
Ninety-five eyes of 51 consecutive patients were evaluated in this retrospective cross-sectional pilot study. Cirrus 5-line raster SD-OCTs with a resolution of 5 to 15 μm obtained through the ONH were included. A single observer manually measured neural canal opening (NCO), prelaminar canal depth (PLCD), peripapillary choroidal thickness (PPCT), and canal nerve fiber layer (CNFL) in normals, ocular hypertension, primary open-angle glaucoma (POAG), low-pressure glaucoma (LPG), secondary glaucoma, and early atrophic age-related macular degeneration. Clinical information, including central corneal thickness (CCT), was obtained via medical record review. Mean anatomical values within diagnosis categories were compared using one-way analysis of variance and multivariate analysis. Bivariate analysis was used to investigate relationships between continuous variables, and significant (p < 0.05) relationships were incorporated into the final statistical model.
Horizontal NCO was significantly greater in eyes with LPG than that in normals (p = 0.021). The PPCT was thinner in age-related macular degeneration (p = 0.001) and glaucoma (p = 0.004) compared with that in controls (normals). Mean CNFL was thinner in POAG (p < 0.001) and LPG (p = 0.053) compared with that in normals. Vertical NCO was inversely correlated to CCT (p = 0.013). Multivariate analysis indicated a positive correlation between PLCD and PPCT (p = 0.008) and an inverse correlation between CNFL and PLCD (p < 0.001). Controlling for PPCT, PLCD and CCTwere inversely correlated (p < 0.001).
The SD-OCT raster scanning may be used to quantify ONH anatomy in humans. The NCO differences between POAG and LPG may indicate a distinct structural vulnerability in LPG. In addition, CNFL, PPCT, and PLCD may be important parameters to consider in glaucoma. The PLCD correlates with PPCT and should be considered in new models of glaucoma pathogenesis.
PMCID: PMC3775484  PMID: 23232801
Fourier domain OCT; spectral domain OCT; SD-OCT; low-pressure glaucoma; optic disc size; prelaminar canal depth; peripapillary choroidal thickness
11.  Comparison of retinal nerve fibre layer thickness and visual field loss between different glaucoma groups 
The British Journal of Ophthalmology  2005;89(8):1004-1007.
Background/aims: Scanning laser polarimetry (SLP) uses a confocal scanning laser ophthalmoscope with an integrated polarimeter to evaluate the thickness of the retinal nerve fibre layer (RNFL). The aim of this study was to verify the ability of the SLP to detect differences in RNFL thickness between normal and glaucomatous eyes and between glaucomatous eyes subdivided in groups by the severity of visual field damage.
Methods: This was a cross sectional retrospective study. The charts of 40 healthy subjects and 68 glaucoma patients who underwent complete ophthalmological examination, optic disc stereophotography, peripapillary, and macular SLP imaging were reviewed. The right eye of subjects eligible for the study was enrolled. Only eyes with SLP examinations indicating a minimised effect of anterior segment birefringence based on macular image were included. The ability of retardation parameters to discriminate between healthy and glaucomatous eyes was evaluated. Based on visual field loss, glaucoma patients were subdivided in three subgroups (early, moderate, and severe). RNFL thickness between healthy control group and glaucoma subgroups was compared. RNFL thickness and visual field loss correlation was evaluated.
Results: There was a significant difference in superior and inferior maximum RNFL thickness between normal and glaucomatous eyes (p<0.001). With these two parameters, the area under receiver operator characteristic curve was 0.75 and 0.74, respectively. Superior and inferior RNFL thickness was significantly different between healthy control group and all glaucoma subgroups (p<0.001) and between glaucoma subgroups (p<0.05), except for early and moderate glaucoma subgroups (p>0.05). Linear regression showed a weak correlation between RNFL thickness and visual field loss.
Conclusion: These results suggest that once visual field loss is established, smaller reductions in the RNFL thickness detected by SLP are necessary for a given reduction of mean defect value.
PMCID: PMC1772786  PMID: 16024854
retinal nerve fibre layer; glaucoma; visual field loss
12.  Study of retinal nerve fibre layer thickness in eyes with high tension glaucoma and hemifield defect 
The British Journal of Ophthalmology  2001;85(10):1167-1170.
AIM—To quantitatively evaluate retinal nerve fibre layer (RNFL) difference in areas of apparently normal appearing visual field in eyes with high tension glaucoma (HTG) and hemifield defects using scanning laser polarimetry.
METHODS—40 eyes from 40 patients with HTG with superior or inferior hemifield defects based on the Humphrey field analyser (HFA) underwent RNFL thickness measurements. 20 normal eyes from 20 subjects matched in age and refractive error were selected as a control group. The RNFL thickness was measured with a scanning laser polarimeter. Mean RNFL thickness was evaluated in four quadrants (superior, inferior, nasal, and temporal). A superior or inferior quadrant in the defined ring of scanning laser polarimetry corresponds to inferior or superior hemifield in HFA.
RESULTS—The mean RNFL thickness in the unaffected quadrant (the quadrant corresponding to the hemifield with apparently normal visual field based on HFA) of the HTG group was significantly thinner than the average RNFL thickness of the corresponding quadrant of the control eyes. The RNFL thickness of the unaffected quadrant in the eyes with HTG was reduced and statistically similar to that of the affected quadrant. Symmetry, calculated as the ratio of superior to inferior RNFL thickness, showed no statistical difference between the study and control group.
CONCLUSION—Changes in RNFL are present in the apparently normal hemifield in the eyes with HTG. The thickness of the RNFL is reduced symmetrically in both superior and inferior quadrants based on the GDx parameters.

PMCID: PMC1723743  PMID: 11567958
13.  Assessment of Choroidal Thickness in Healthy and Glaucomatous Eyes Using Swept Source Optical Coherence Tomography 
PLoS ONE  2014;9(10):e109683.
To evaluate choroidal thickness (CT) in healthy and glaucomatous eyes using Swept Source Optical Coherence Tomography (SS-OCT).
A cross-sectional observational study of 216 eyes of 140 subjects with glaucoma and 106 eyes of 67 healthy subjects enrolled in the Diagnostic Innovations in Glaucoma Study. CT was assessed from wide-field (12×9 mm) SS-OCT scans. The association between CT and potential confounding variables including age, gender, axial length, intraocular pressure, central corneal thickness and ocular perfusion pressure was examined using univariable and multivariable regression analyses.
Overall CT was thinner in glaucomatous eyes with a mean (± standard deviation) of 157.7±48.5 µm in glaucoma compared to 179.9±36.1 µm in healthy eyes (P<0.001). The choroid was thinner in both the peripapillary and macular regions in glaucoma compared to controls. Mean peripapillary CT was 154.1±44.1 µm and 134.0±56.9 µm (P<0.001) and macular CT 199.3±46.1 µm and 176.2±57.5 µm (P<0.001) for healthy and glaucomatous eyes respectively. However, older age (P<0.001) and longer axial length (P<0.001) were also associated with thinner choroid and when differences in age and axial length between glaucomatous and healthy subjects were accounted for, glaucoma was not significantly associated with CT. There was also no association between glaucoma severity and CT.
Glaucoma was not associated with CT measured using SS-OCT; however, older age and longer axial length were associated with thinner choroid so should be considered when interpreting CT measurements.
PMCID: PMC4190357  PMID: 25295876
14.  Comparison of optic nerve morphology in eyes with glaucoma and eyes with non-arteritic anterior ischemic optic neuropathy by Fourier domain optical coherence tomography 
The aim of this study was to compare the optic nerve head (ONH) and peripapillary retinal nerve fiber layer (RNFL) thickness in eyes with glaucoma and non-arteritic anterior ischemic neuropathy (NAION) by Fourier domain optical coherence tomography (FDOCT), and to evaluate the diagnostic capability of FDOCT in glaucoma and NAION. This study included 26 eyes with glaucoma (36.6%), 15 eyes with NAION (21.1%) and 30 eyes of normal subjects (42.3%). Those with the following conditions were excluded; a visual field defect greater than one hemifield, spherical equivalent (SE) more than ±6 D, or the onset of NAION within 6 months. FDOCT was used to analyze the characteristics of ONH and RNFL thickness. Among the three groups of subjects, glaucomatous eyes had the largest cup area and cup volume, and the smallest rim area, rim volume and disc volume (P<0.05). NAION eyes had the smallest cup area and cup volume (P<0.05), but their rim area, rim volume and disc volume were comparable to those of control eyes (P>0.05). The cup-to-disc (C/D) ratio was increased in glaucomatous eyes but reduced in NAION eyes compared with control eyes. Glaucomatous eyes had the greatest loss of RNFL thickness in the temporal upper (TU), superior temporal (ST) and temporal lower (TL) regions (P<0.05), whereas NAION eyes had the smallest RNFL thickness in the superior nasal (SN) and nasal upper (NU) regions (P<0.05). The areas under the receiver operator characteristic curve (AROCs) of the temporal, superior and inferior RNFL in glaucomatous eyes were greater compared with that of the disc area (P<0.05). In addition, the AROCs of the temporal, superior and inferior RNFL were higher compared with that of nasal RNFL (P<0.05). The AROCs of all parameters for NAION were not significantly different, with the exception of superior, nasal superior and inferior temporal RNFL (P<0.05). In conclusion, FDOCT is able to detect quantitative differences in the optic disc morphology and RNFL thickness between glaucomatous and NAION eyes. These differences may provide new insights into the clinical characteristics and diagnosis of the two diseases.
PMCID: PMC3735902  PMID: 23935759
optic disc; retinal nerve fiber layer; glaucoma; ischemic optic neuropathy; optic coherence tomography
15.  Comparison of Retinal Nerve Fiber Layer Thickness between Stratus and Spectralis OCT 
To compare the peripapillary retinal nerve fiber layer (RNFL) thickness of normal patients and those with various glaucoma diseases by time domain (Stratus) and spectral domain (Spectralis) optical coherence tomography (OCT).
The RNFL thickness as measured by the Stratus and Spectral OCT was compared (paired t-test). The relationship and agreement of RNFL thickness between the two OCT modalities were evaluated by Pearson correlation, Bland-Altman plot, and area under the receiver operating characteristic curve.
Two-hundred seventeen eyes of 217 patients, including twenty-four normal eyes, ninety-one glaucoma suspects, seventy-six normal tension glaucoma cases, and twenty-six primary open angle glaucoma cases (POAG) were analyzed. The peripapillary RNFL thicknesses as measured by Stratus OCT were significantly greater than those measured by Spectralis OCT. However, in quadrant comparisons, the temporal RNFL thickness obtained using Stratus OCT were significantly less than those obtained using Spectralis OCT. Correlations between RNFL parameters were strong (Pearson correlation coefficient for mean RNFL thickness = 0.88); a high degree of correlation was found in the POAG group. Bland-Altman plotting demonstrated that agreement in the temporal quadrant was greater than any other quadrant.
Both OCT systems were highly correlated and demonstrated strong agreement. However, absolute measurements of peripapillary RNFL thickness differed between Stratus OCT and Spectralis OCT. Thus, measurements with these instruments should not be considered interchangeable. The temporal quadrant was the only sector where RNFL thickness as measured by Spectralis OCT was greater than by Stratus OCT; this demonstrated greater agreement than other sectors.
PMCID: PMC3102819  PMID: 21655041
Retinal nerve fiber layer thickness; Spectral domain optical coherence tomography; Time domain optical coherence tomography
16.  Correlation between peripapillary retinal nerve fiber layer thickness and fundus autofluorescence in primary open-angle glaucoma 
To investigate the relationship between retinal nerve fiber layer (RNFL) thickness and retinal pigment epithelium alterations in patients with advanced glaucomatous visual field defects.
A consecutive, prospective series of 82 study eyes with primary open-angle glaucoma and advanced glaucomatous visual field defects were included in this study. All study participants underwent a full ophthalmic examination followed by visual field testing with standard automated perimetry as well as spectral-domain optical coherence tomography (SD-OCT) for peripapillary RNFL thickness and Optos wide-field fundus autofluorescence (FAF) images. A pattern grid with corresponding locations between functional visual field sectors and structural peripapillary RNFL thickness was aligned to the FAF images at corresponding location. Mean FAF intensity (range: 0 = black and 255 = white) of each evaluated sector (superotemporal, temporal, inferotemporal, inferonasal, nasal, superonasal) was correlated with the corresponding peripapillary RNFL thickness obtained with SD-OCT.
Correlation analyses between sectoral RNFL thickness and standardized FAF intensity in the corresponding topographic retina segments revealed partly significant correlations with correlation coefficients ranging between 0.004 and 0.376 and were statistically significant in the temporal inferior central field (r = 0.324, P = 0.036) and the nasal field (r = 0.376, P = 0.014).
Retinal pigment epithelium abnormalities correlate with corresponding peripapillary RNFL damage, especially in the temporal inferior sector of patients with advanced glaucomatous visual field defects. A further evaluation of FAF as a potential predictive parameter for glaucomatous damage is necessary.
PMCID: PMC3788816  PMID: 24092967
glaucoma; fundus autofluorescence; FAF; retinal nerve fiber layer; RNFL; optical coherence tomography; OCT; imaging
17.  Optical coherence tomography of superior segmental optic hypoplasia 
Aim: To describe optical coherence tomography (OCT) images of superior segmental optic hypoplasia (SSOH).
Methods: Five patients (two men and three women, ages 10–45 years) presented with ophthalmoscopic features and visual field defects of SSOH. All affected eyes had good visual acuity and inferior altitudinal or inferonasal visual field loss. The mothers of three patients had type 1 diabetes mellitus. OCT (Humphrey Instrument, CA, USA) was used to evaluate tomographically the optic disc and peripapillary retina of both eyes of each patient. Control data on retinal nerve fibre layer (RNFL) thickness were obtained from 13 normal eyes, one eye each from 13 normal subjects.
Results: Seven of 10 eyes in patients had SSOH. Scans in the vertical meridian through the affected optic discs showed a superior defect of the optic disc associated with decreased RNFL thickness and, in some cases, an abnormal extension of a complex of retinal pigment epithelium and choroid over the edge of the lamina cribrosa. Circular scans around the seven optic discs revealed various decreases of peripapillary RNFL thickness in the superior quadrants. Vertical scans through the fovea also showed superior thinning of RNFL. Quantitative assessment of the peripapillary RNFL thickness revealed significantly decreased values in the superior quadrants compared to normal eyes.
Conclusions: OCT provides a new tool for quantitative evaluation of optic nerve hypoplasia as exemplified in this study of SSOH. It can reveal minimal degrees of segmental hypoplasia previously undetected.
PMCID: PMC1771231  PMID: 12140214
optical coherence tomography; optic hypoplasia
18.  Evaluation of the Macular, Peripapillary Nerve Fiber Layer and Choroid Thickness Changes in Behçet's Disease with Spectral-Domain OCT 
Journal of Ophthalmology  2014;2014:865394.
Purpose. To assess the macular, choroid, and peripapillary nerve fiber layer thickness (RNFL) in Behçet's disease (BD) patients with and without ocular involvement by means of optical coherence tomography (OCT) and compare these findings with healthy controls. Design. Eighty patients with BD and 40 healthy controls who were followed up at the Uveitis and Retina Clinic of the Kayseri Research and Education Hospital in Turkey were enrolled in this prospective study. Subjects and Controls. The patients with BD were divided into two groups according to the presence of ocular involvement. Group 1 consisted of 40 eyes of 40 patients with ocular involvement and group 2 consisted of 40 eyes of 40 patients without ocular involvement. Methods. All of the patients and controls underwent macular, choroid, and peripapillary nerve fiber layer thickness analysis with Spectralis domain OCT (Spectralis OCT Heidelberg Engineering, Dossenheim, Germany). Main Outcome Measures. The differences in macular, choroid, and peripapillary nerve fiber layer thicknesses between groups were analyzed statistically. Results. Macular thickness was thinner in patients with BD than in the control group; this result was statistically significant (P = 0.05). There was no statistically significant difference in thickness between RNFL analysis of the patients with BD and control subjects. However, the BD patients with ocular involvement had statistically significant thinning in RNFL compared with BD patients without ocular involvement. Although the choroid was thicker in patients with BD than in the control group, it did not reach a statistically significant level (P = 0.382). Conclusions. BD with ocular involvement may be associated with decreased macular and RNFL thickness measured with spectral-domain OCT.
PMCID: PMC4020218  PMID: 24868459
19.  Measurement of retinal nerve fibre layer by scanning laser polarimetry and high pass resolution perimetry in normal tension glaucoma with relatively high or low intraocular pressure 
AIMS—To determine whether any differences may exist in the relation between the neural capacity as determined by high pass resolution perimetry and the thickness of the retinal nerve fibre layer (RNFL) in patients having normal tension glaucoma (NTG) with a relatively high intraocular pressure (IOP) between 16 and 21 mm Hg (HNTG) v those with a lower IOP below 15 mm Hg (LNTG).
METHODS—Scanning laser polarimetry and high pass resolution perimetry were performed in 20 eyes of 20 patients with HNTG and 21 eyes of 21 patients with LNTG. The correlation between total and regional thickness of the peripapillary RNFL and the corresponding total and regional neural capacity with linear regression analysis were evaluated.
RESULTS—Overall, although the total RNFL thickness was not significantly correlated with the total neural capacity, the RNFL thickness in each of the superior and inferior quadrants was significantly correlated with the corresponding regional neural capacity (r=0.44, p=0.0045; r=0.39, p=0.0126 for each). The RNFL thickness in each of the superior and inferior quadrants in the HNTG group was significantly correlated with the corresponding regional neural capacity (r=0.52, p=0.0196; r=0.49, p=0.0286 for each). No significant correlation between neural capacity and the RNFL thickness was observed either globally or regionally in the LNTG group.
CONCLUSION—The degree of the correlation between neural capacity as determined by high pass resolution perimetry and thickness of the RNFL as measured by scanning laser polarimetry appeared to differ in NTG patients with an IOP higher than 15 mm Hg v those with a lower IOP.

 Keywords: scanning laser polarimetry; high pass resolution perimetry; normal tension glaucoma
PMCID: PMC1722974  PMID: 10365047
20.  Diabetic Retinopathy and Peripapillary Retinal Thickness 
To assess the diagnostic efficacy of macular and peripapillary retinal thickness measurements for the staging of diabetic retinopathy (DR) and the prediction of disease progression.
In this prospective study, 149 diabetic patients (149 eyes) and 50 non-diabetic control subjects were included. Baseline optical coherence tomography was employed to measure retinal thickness in the macula (horizontal, vertical, and central) and the peripapillary zone (superior, inferior, nasal, and concentric to the optic disc). Seven baseline parameters were correlated with the DR stages identified by fluorescein angiography. Baseline retinal thickness was compared between groups of patients requiring panretinal photocoagulation (PRP) within 6 months (PRP group) and patients not requiring PRP (No-PRP group).
Macular and peripapillary retinal thicknesses in diabetic subjects were significantly greater than that in normal controls (p<0.05). All retinal thickness parameters, and particularly peripapillary circular scans, tended to increase with increasing DR severity (p<0.05). The baseline thicknesses of the peripapillary circular scans were greater in the PRP group than in the no-PRP group (p<0.05).
Peripapillary retinal thickness may prove to be a useful criterion for DR severity and may also serve as an indicator of disease progression.
PMCID: PMC2817818  PMID: 20157409
Diabetic retinopathy; Laser photocoagulation; Retina; Mass screening
21.  Ability of Cirrus™ HD-OCT Optic Nerve Head Parameters to Discriminate Normal from Glaucomatous Eyes 
Ophthalmology  2010;118(2):241-248.e1.
To determine the ability of optic nerve head (ONH) parameters measured with spectral domain Cirrus™ HD-OCT to discriminate between normal and glaucomatous eyes and to compare them to the discriminating ability of peripapillary retinal nerve fiber layer (RNFL) thickness measurements performed with Cirrus™ HD-OCT.
Evaluation of diagnostic test or technology.
Seventy-three subjects with glaucoma and one hundred and forty-six age-matched normal subjects.
Peripapillary ONH parameters and RNFL thickness were measured in one randomly selected eye of each participant within a 200×200 pixel A-scan acquired with Cirrus™ HD-OCT centered on the ONH.
Main Outcome Measures
ONH topographic parameters, peripapillary RNFL thickness, and the area under receiver operating characteristic curves (AUCs).
For distinguishing normal from glaucomatous eyes, regardless of disease stage, the six best parameters (expressed as AUC) were vertical rim thickness (VRT, 0.963), rim area (RA, 0.962), RNFL thickness at clock-hour 7 (0.957), RNFL thickness of the inferior quadrant (0.953), vertical cup-to-disc ratio (VCDR, 0.951) and average RNFL thickness (0.950). The AUC for distinguishing between normal and eyes with mild glaucoma was greatest for RNFL thickness of clock-hour 7 (0.918), VRT (0.914), RA (0.912), RNFL thickness of inferior quadrant (0.895), average RNFL thickness (0.893) and VCDR (0.890). There were no statistically significant differences between AUCs for the best ONH parameters and RNFL thickness measurements (p > 0.05).
Cirrus™ HD-OCT ONH parameters are able to discriminate between eyes that are normal from those with glaucoma or even mild glaucoma. There is no difference in the ability of ONH parameters and RNFL thickness measurement, as measured with Cirrus™ OCT, to distinguish between normal and glaucomatous eyes.
PMCID: PMC3017237  PMID: 20920824
22.  Frequency doubling technique perimetry and spectral domain optical coherence tomography in patients with early glaucoma 
Eye  2010;25(1):17-29.
To assess the combined diagnostic power of frequency-doubling technique (FDT)-perimetry and retinal nerve fibre layer (RNFL) thickness measurements with spectral domain optical coherence tomography (SDOCT).
The study included 330 experienced participants in five age-related groups: 77 ‘preperimetric' open-angle glaucoma (OAG) patients, 52 ‘early' OAG, 50 ‘moderate' OAG, 54 ocular hypertensivepatients, and 97 healthy subjects. For glaucoma assessment in all subjects conventional perimetry, evaluation of fundus photographs, FDT-perimetry and RNFL thickness measurement with SDOCT was done. Glaucomatous visual field defects were classified using the Glaucoma Staging System. FDT evaluation used a published method with casewise calculation of an ‘FDT-score', including all missed localized probability levels. SDOCT evaluation used mean RNFL thickness and a new individual SDOCT-score considering normal confidence limits in 32 sectors of a peripapillary circular scan. To examine the joined value of both methods a combined score was introduced. Significance of the difference between Receiver-operating-characteristic (ROC) curves was calculated for a specificity of 96%.
Sensitivity in the preperimetric glaucoma group was 44% for SDOCT-score, 25% for FDT-score, and 44% for combined score, in the early glaucoma group 83, 81, and 89%, respectively, and in the moderate glaucoma group 94, 94, and 98%, respectively, all at a specificity of 96%. ROC performance of the newly developed combined score is significantly above single ROC curves of FDT-score in preperimetric and early OAG and above RNFL thickness in moderate OAG.
Combination of function and morphology by using the FDT-score and the SDOCT-score performs equal or even better than each single method alone.
PMCID: PMC3144638  PMID: 21102494
early glaucoma; frequency doubling technique; perimetry; retinal nerve fibre layer thickness; spectral domain OCT
23.  The role of hemifield sector analysis in multifocal visual evoked potential objective perimetry in the early detection of glaucomatous visual field defects 
The purpose of this study was to examine the effectiveness of a new analysis method of mfVEP objective perimetry in the early detection of glaucomatous visual field defects compared to the gold standard technique.
Methods and patients
Three groups were tested in this study; normal controls (38 eyes), glaucoma patients (36 eyes), and glaucoma suspect patients (38 eyes). All subjects underwent two standard 24-2 visual field tests: one with the Humphrey Field Analyzer and a single mfVEP test in one session. Analysis of the mfVEP results was carried out using the new analysis protocol: the hemifield sector analysis protocol.
Analysis of the mfVEP showed that the signal to noise ratio (SNR) difference between superior and inferior hemifields was statistically significant between the three groups (analysis of variance, P < 0.001 with a 95% confidence interval, 2.82, 2.89 for normal group; 2.25, 2.29 for glaucoma suspect group; 1.67, 1.73 for glaucoma group). The difference between superior and inferior hemifield sectors and hemi-rings was statistically significant in 11/11 pair of sectors and hemi-rings in the glaucoma patients group (t-test P < 0.001), statistically significant in 5/11 pairs of sectors and hemi-rings in the glaucoma suspect group (t-test P < 0.01), and only 1/11 pair was statistically significant (t-test P < 0.9). The sensitivity and specificity of the hemifield sector analysis protocol in detecting glaucoma was 97% and 86% respectively and 89% and 79% in glaucoma suspects. These results showed that the new analysis protocol was able to confirm existing visual field defects detected by standard perimetry, was able to differentiate between the three study groups with a clear distinction between normal patients and those with suspected glaucoma, and was able to detect early visual field changes not detected by standard perimetry. In addition, the distinction between normal and glaucoma patients was especially clear and significant using this analysis.
The new hemifield sector analysis protocol used in mfVEP testing can be used to detect glaucomatous visual field defects in both glaucoma and glaucoma suspect patients. Using this protocol, it can provide information about focal visual field differences across the horizontal midline, which can be utilized to differentiate between glaucoma and normal subjects. The sensitivity and specificity of the mfVEP test showed very promising results and correlated with other anatomical changes in glaucomatous visual field loss. The intersector analysis protocol can detect early field changes not detected by the standard Humphrey Field Analyzer test.
PMCID: PMC3656925  PMID: 23690675
objective perimetry; multifocal VEP; visual field testing; glaucomatous field loss; glaucoma suspect; SAP; HFA
24.  Central corneal thickness measurements in patients with normal tension glaucoma, primary open angle glaucoma, pseudoexfoliation glaucoma, or ocular hypertension 
BACKGROUND/AIMS—Recent studies have revealed patients with ocular hypertension to have thicker than normal central corneas and those with normal tension glaucoma to have thinner than normal ones, as determined by ultrasonic pachymetry. Since corneal thickness measurements and applanation tonometric estimates of intraocular pressure (IOP) correlate positively, monitoring of the former parameter have served as the basis for adjusting readings pertaining to the latter, with the consequence that many patients have had to be reclassified. With a view to validating these pachymetric studies, the central corneal thickness was determined in patients with normal tension glaucoma, primary open angle glaucoma, pseudoexfoliation glaucoma, or ocular hypertension, as well as that of normal subjects, using optical low coherence reflectometry, which is a new and more precise method than ultrasonic pachymetry.
METHODS—34 patients with normal tension glaucoma, 20 with primary open angle glaucoma, 13 with pseudoexfoliation glaucoma, and 12 with ocular hypertension, together with 21 control subjects, were included in this observational, concurrent case-control study. One eye per individual was randomly selected for investigation. IOP was measured by Goldmann applanation tonometry and central corneal thickness by optical low coherence reflectometry.
RESULTS—Central corneal thickness was significantly higher (p ⩽0.001) in patients with ocular hypertension than in normal individuals or in subjects with either normal tension glaucoma, primary open angle glaucoma, or pseudoexfoliation glaucoma, there being no significant differences between the latter four groups. Patients with ocular hypertension were also significantly younger (p ⩽0.003) than those within any of the three glaucomatous groups.
CONCLUSION—This study confirms that a significant number of patients with ocular hypertension have normal IOPs after the appropriate adjustments have been made for deviations from normal in their central corneal thickness. The accurate measurement of this latter parameter is important not only for individual patient care, in permitting more precise estimations of IOP, but also for clinical studies, in assuring a more reliable classification of subjects.

PMCID: PMC1724054  PMID: 11423450
25.  Relationship between Spectral-Domain Optical Coherence Tomography and Standard Automated Perimetry in Healthy and Glaucoma Patients 
BioMed Research International  2014;2014:514948.
Objective. To evaluate the relationship between spectral-domain optical coherence tomography (OCT) and standard automated perimetry (SAP) in healthy and glaucoma individuals. Methods. The sample comprised 338 individuals divided into 2 groups according to intraocular pressure and visual field outcomes. All participants underwent a reliable SAP and imaging of the optic nerve head with the Cirrus OCT. Pearson correlations were calculated between threshold sensitivity values of SAP (converted to linear scale) and OCT parameters. Results. Mean age did not differ between the control and glaucoma groups (59.55 ± 9.7 years and 61.05 ± 9.4 years, resp.; P = 0.15). Significant differences were found for the threshold sensitivities at each of the 52 points evaluated with SAP (P < 0.001) and the peripapillary retinal nerve fiber layer (RNFL) thicknesses, except at 3 and 9 clock-hour positions between both groups. Mild to moderate correlations (ranging between 0.286 and 0.593; P < 0.001) were observed between SAP and most OCT parameters in the glaucoma group. The strongest correlations were found between the inferior RNFL thickness and the superior hemifield points. The healthy group showed lower and weaker correlations than the glaucoma group. Conclusions. Peripapillary RNFL thickness measured with Cirrus OCT showed mild to moderate correlations with SAP in glaucoma patients.
PMCID: PMC4083774  PMID: 25028657

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