Biomarkers.

Evaluation of optic coherence tomography findings in patients with inflammatory bowel disease

Glaucoma progression rates may differ depending on the retinal structural parameters measured, and between devices. To compare retinal nerve fibre layer (RNFL) and ganglion cell/inner plexiform layers (GCL/IPL) progression rates using two spectral-domain optical coherence tomography (OCT) systems. Prospective, university hospital setting. Cross-sectional study: 100 eyes from 53 glaucoma suspects and early manifest glaucoma cases. Longitudinal study: subset of 61 eyes from 33 participants. Same day optic nerve and macular images were acquired using Cirrus and Spectralis systems from which RNFL and GCL/IPL thicknesses were calculated. Longitudinal analysis of RNFL and GCL/IPL progression rates was calculated from 6 × 6-monthly follow-up OCT scans. RNFL and GCL/IPL thicknesses in matched superior, inferior and global regions were compared by both systems cross-sectionally and longitudinally. At baseline, no RNFL thicknesses differed between devices. Cirrus GCL/IPL regions were significantly thicker than Spectralis (P < .001). RNFL and GCL/IPL global progression rates (μm/y) had a mean (SD) of -1.28 (1.11) and 95% CI: (-1.48, -1.09) and -0.51 (0.58) and 95% CI: (-0.62, -0.41), respectively. Progression rates were similar across devices. RNFL loss (%) progressed significantly faster than GCL/IPL, in all regions (P ≤ .004). Despite baseline thickness differences, overall Cirrus and Spectralis provided similar rates of RNFL and GCL/IPL progression in early glaucoma and can be considered comparable, though not interchangeable, in clinical practice. Further analysis is needed to determine if RNFL progresses faster than GCL/IPL in glaucoma, and whether one precedes the other.

To study the distribution of macular ganglion cell-inner plexiform layer (GC-IPL) thickness and peripapillary retinal nerve fiber layer (RNFL) thickness in children with refractive errors. Two hundred forty-three healthy eyes from 139 children with refractive error ranging from -10.00 to +5.00 D were recruited from the National University Hospital Eye Surgery outpatient clinic. After a comprehensive ocular examination, refraction, and axial length (AL) measurement (IOLMaster), macular GC-IPL and RNFL thickness values were obtained with a spectral domain Cirrus high definition optical coherence tomography system (Carl Zeiss Meditec Inc.). Only scans with signal strength of >6/10 were included. Correlation between variables was calculated using the Pearson correlation coefficient. A multivariate analysis using mixed models was done to adjust for confounders. The mean spherical equivalent refraction was -3.20±3.51 D and mean AL was 24.39±1.72 mm. Average, minimum, superior, and inferior GC-IPL were 82.59±6.29, 77.17±9.65, 83.68±6.96, and 81.64±6.70 μm, respectively. Average, superior, and inferior peripapillary RNFL were 99.00±11.45, 123.20±25.81, and 124.24±22.23 μm, respectively. Average, superior, and inferior GC-IPL were correlated with AL (β=-2.056, P-value 0.000; β=-2.383, P-value 0.000; β=-1.721, P-value 0.000), but minimum GC-IPL was not (β=-1.056, P-value 0.115). None of the RNFL parameters were correlated with AL. This study establishes normative macular GC-IPL and RNFL thickness in children with refractive errors. Our results suggest that high definition optical coherence tomography RNFL parameters and minimum GC-IPL are not affected by AL or myopia in children, and therefore warrants further evaluation in pediatric glaucoma patients.

Influence of Cataract Surgery on Optical Coherence Tomography and Neurophysiology Measurements in Patients With Retinitis Pigmentosa

Objective: To evaluate the effect of tumor necrosis factor-alpha (TNF-α) blockade on the thickness of the peripapillary retinal nerve fiber layer (RNFL), the ganglion cell-inner plexiform layers (GCIPL), and the macula in ankylosing spondylitis (AS) patients under anti-TNF-α therapy.Materials and methods: Twenty-one patients with AS received etanercept, or adalimumab, or infliximab for at least 6 months. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores were measured before and 6 months after the beginning of the treatment. Peripapillary RNFL, four regional fields (superior, inferior, nasal, and temporal), GCIPL, and macular thicknesses of the patients were analyzed by optical coherence tomography before the treatment, at 3 months and 6 months after the beginning of the treatment.Results: The mean BASDAI, ESR, and CRP values were 5.2 ± 1.5, 31.6 ± 21.7, and 15.7 ± 13.9, respectively, at the beginning of the treatment and 2.3 ± 1.7, 21.3 ± 15.1, and 10.1 ± 10.3, respectively, 6 months after the beginning of treatment. There were significant differences among the mean BASDAI, ESR, and CRP values at the beginning of treatment and 6 months later (p < 0.001, p = 0.007, and p = 0.009, respectively). There were no significant differences among peripapillary RNFL (p = 0.24), four regional fields (p = 0.98, p = 0.23, p = 0.09, p = 0.47), GCIPL (p = 0.25), or macular (p = 0.33) thicknesses of the patients during anti-TNF-α treatment. In addition, the mean intraocular pressure levels throughout the follow-up did not show significant variation on repeated-measures ANOVA (p = 0.77).Conclusions: TNF-α blockade does not seem to influence RNFL, GCIPL, or macular thickness of patients with AS in the short term.

PurposeThe purpose of this study was to investigate associations between cardiovascular risk factors and the thickness of retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GCIPL), and outer retina layers (ORL).MethodsIn this population-based study, we included participants from the Tromsø Study: Tromsø6 (2007 to 2008) and Tromsø7 (2015 to 2016). Persons with diabetes and/or diagnosed glaucoma were excluded from this study. Retinal thickness was measured on optical coherence tomography (Cirrus HD-OCT) macula-scans, segmented on RNFL, GCIPL, and ORL and associations were analyzed cross-sectionally (N = 8288) and longitudinally (N = 2595). We used directed acyclic graphs (DAGs) for model selection, and linear regression to adjust for confounders and mediators in models assessing direct effects. Factors examined were age, sex, blood pressure, daily smoking, serum lipids, glycated hemoglobin, body mass index (BMI), total body fat percentage (BFP), and the adjustment variables refraction and height.ResultsThe explained variance of cardiovascular risk factors was highest in GCIPL (0.126). GCIPL had a strong negative association with age. Women had thicker GCIPL than men at higher age and thinner ORL at all ages (P < 0.001). Systolic blood pressure was negatively associated with RNFL/GCIPL (P = 0.001/0.004), with indication of a U-shaped relationship with GCIPL in women. The negative association with BMI was strongest in men, with significant effect for RNFL/GCIPL/ORL (P = 0.001/<0.001/0.019) and in women for GCIPL/ORL (P = 0.030/0.037). BFP was negatively associated with GCIPL (P = 0.01). Higher baseline BMI was associated with a reduction in GCIPL over 8 years (P = 0.03).ConclusionsCardiovascular risk factors explained 12.6% of the variance in GCIPL, with weight and blood pressure the most important modifiable factors.

To evaluate progressive changes in retinal nerve fibre layer (RNFL), ganglion cell layer/inner plexiform layer (GCL/IPL) and visual function in thyroid eye disease (TED) patients with and without orbital decompression. Sixty TED patients (105 eyes) were included. All patients were divided into mild, moderate-to-severe and dysthyroid optic neuropathy (DON) groups. Orbital decompression was performed in the moderate-to-severe and DON groups. Optic coherence tomography (OCT), visual field (VF) and best-corrected visual acuity (BCVA) were performed pre- and postoperatively. Preoperative follow-up was performed in the mild group and in part of the moderate-to-severe and DON groups. After decompression, the thickness of GCL/IPL and RNFL significantly decreased in DON group (p < 0.05), with varying degrees of decrease in eyes with optic disc swelling, atrophy and normal appearance. The mean GCL/IPL thickness significantly decreased in moderate-to-severe group (p < 0.05), the mean RNFL thickness slightly decreased with no statistical significance (p = 0.07). During the preoperative follow-ups, the mean GCL/IPL thickness significantly decreased (p = 0.04), whereas the mean RNFL thickness tended to increase (p = 0.13) in DON group. The thickness of GCL/IPL and RNFL did not change significantly in the mild and moderate-to-severe groups (p > 0.05). BCVA and VF did not change significantly in any group (p > 0.05) preoperatively. Swelling and degeneration of retinal ganglion cells (RGCs) may coexist in DON eyes, leading to continuous changes in the RNFL and GCL/IPL thickness either before or after decompression. Slight swelling and degeneration of RGCs may exist in moderate-to-severe TED eyes, although OCT measurements and visual functions remain stable before surgery.

To determine the sensitivity of manufacturer supported normative algorithms in Heidelberg retinal tomography (HRT) and Stratus optical coherence tomography (OCT) in detecting advanced primary open angle glaucoma. A total of 157 subjects with advanced primary open angle glaucoma were recruited. The eye with the more severe glaucoma, as judged by mean deviation on Humphrey visual field, was imaged. The total number of optic disc sectors classified as being outside normal limits on Moorfields Regression Analysis (MRA) from the HRT II and HRT 3 software or from the sector and quadrant averages analysis of the Retinal Nerve Fiber Layer OCT scans was compared using the Wilcoxon signed ranks test. At least one segment in each eye was identified as being outside normal limits by the OCT sector Retinal Nerve Fiber Layer analysis (100% sensitivity). Five eyes were classified as being within normal limits on the OCT quadrant average analysis (96.8% sensitivity). Four eyes were found to be either completely within normal limits or borderline on the HRT II MRA (97.5% sensitivity), of which one was subsequently identified as being outside normal limits by the HRT 3 MRA. The total number of segments classified as being outside normal limits was greater on HRT 3 MRA than HRT II MRA (P < 0.001). Automated optic nerve imaging devices rarely produce a totally normal result in the presence of advanced primary open angle glaucoma. The Stratus OCT Retinal Nerve Fiber Layer clock hour normative database performs better than other modalities studied. These findings are important in considering the utility of these algorithms for community screening.

Optical coherence tomography as a tool for monitoring pediatric pseudotumor cerebri

Optic coherence tomography imaging in preperimetric open angle glaucoma (OAG) differed between young-age-onset and old-age-onset eyes. Inferior and superior quadrants were thinner in young and old-age-onset eyes, respectively. Understanding the specific patterns of early glaucomatous damage based on age-at-onset may improve glaucoma diagnosis and monitoring. To investigate the patterns of retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thinning in preperimetric OAG by optical coherence tomography based on age at onset ("young-age onset (<40y)" vs. "old-age onset (≥40y)". The RNFL and GCIPL deviation images were acquired by Cirrus HD-optical coherence tomography, and overlaid, thus converted to a "deviation frequency map", respectively. The topographic thinning patterns and parameters of RNFL and GCIPL thickness measurements were compared. A total of 194 eyes of 194 patients with preperimetric OAG and 97 eyes of 97 age-matched normal subjects were analyzed. Young-age-onset eyes of preperimetric OAG mainly had RNFL defects inferotemporally (264-296 degrees) with GCIPL defects in the inferior region (213-357 degrees). Old-age-onset preperimetric OAG eyes had RNFL defects inferotemporally (266-294°) and superotemporally (33-67 degrees), with GCIPL defects in the inferior and superior regions (206-360 degrees, 0-22 degrees). The inferior quadrant of RNFL and GCIPL thicknesses were significantly thinner in young-age-onset eyes compared with old-age-onset eyes ( P =0.012, 0.016), while the superior quadrant of those were significantly thinner in the old-age-onset eyes ( P =0.003, 0.005). Young-age-onset and old-age-onset eyes of preperimetric OAG present different specific patterns of RNFL and GCIPL thinning.

The purpose of this study was to examine whether application of optical coherence tomography (OCT) measurements can provide a useful biomarker for distinguishing central nervous system (CNS) involvement in autoimmune connective tissue diseases (CTD) from multiple sclerosis (MS). An observational study included non-optic neuritis eyes of 121 individuals: 59 patients with MS, 30 patients with CNS involvement in CTD, and 32 healthy controls. OCT examination was performed in all subjects to measure retinal nerve fiber layer (RNFL) thickness, ganglion cell complex (GCC) thickness, ganglion cell layer-inner plexiform layer (GCIPL) thickness, and volume of the macula. There was a significant group effect with regard to superior optic disc RNFL, macular RNFL, GCC, and GCIPL thickness, and macular volume. Post-hoc analysis revealed that MS patients have significantly smaller macular volume and thinner superior optic disc RNFL, macular RNFL, GCC, and GCIPL compared to healthy controls. CTD patients have significantly smaller superior optic disc RNFL, GCIPL, and GCC thickness compared to healthy controls. However, no significant group differences were observed between the patient groups (MS vs. CTD) on any outcome. Although a prominent retinal thinning may be a useful biomarker in MS patients, in a general population of individuals with a confirmed CNS involvement the use of OCT is not specific enough to discriminate between MS and autoimmune CTD.

The aim of this study was to test the correlation between Fourier-domain (FD) optical coherence tomography (OCT) macular and retinal nerve fibre layer (RNFL) thickness and visual field (VF) loss on standard automated perimetry (SAP) in chiasmal compression. A total of 35 eyes with permanent temporal VF defects and 35 controls underwent SAP and FD-OCT (3D OCT-1000; Topcon Corp.) examinations. Macular thickness measurements were averaged for the central area and for each quadrant and half of that area, whereas RNFL thickness was determined for six sectors around the optic disc. VF loss was estimated in six sectors of the VF and in the central 16 test points in the VF. The correlation between VF loss and OCT measurements was tested with Spearman's correlation coefficients and with linear regression analysis. Macular and RNFL thickness parameters correlated strongly with SAP VF loss. Correlations were generally stronger between VF loss and quadrantic or hemianopic macular thickness than with sectoral RNFL thickness. For the macular parameters, we observed the strongest correlation between macular thickness in the inferonasal quadrant and VF loss in the superior temporal central quadrant (rho=0.78; P<0.001) whereas for the RNFL parameters the strongest correlation was observed between the superonasal optic disc sector and the central temporal VF defect (rho=0.60; P<0.001). Although FD-OCT RNFL and macular thickness measurements were both correlated with VF loss, the correlation was stronger with quadrantic macular than with RNFL thickness measurements in patients with temporal hemianopia. Such measurements could potentially be used to quantify neuronal loss in patients with chiasmal compression.

Purpose: To find the optimal parameter of retinal nerve fiber layer (RNFL) analysis in optical coherence tomography (OCT) for diagnosing glaucoma in children. Methods: The study was comprised of 127 eyes of 84 patients (aged 6 to 18 years) who visited our institute between March 2006 and February 2008. Subjects were classified into normal, glaucoma suspect and glaucoma groups, and each eye was scanned using Stratus 3.0 OCT. Routine ophthalmic examinations including fundus examination, visual field test and OCT RNFL analysis were performed. Results: There were 55 normal eyes, 27 glaucoma suspect eyes and 45 glaucomatous eyes. The average RNFL thickness was the most useful parameter to differentiate between the glaucoma and non-glaucoma groups. The next most useful parameter was inferior average thickness, followed by superior RNFL thickness. The sensitivity and specificity of the new discriminant of the formula used were 78%, and 68.6%, respectively. Conclusions: In OCT analysis, the average RNFL thickness is the most useful parameter in the diagnosis of glaucoma in children. The new discriminant of the formula is useful in the diagnosis of pediatric glaucoma patients.

Retinal structural abnormalities in young adults with psychosis spectrum disorders

Ability of Cirrus High-Definition Spectral-Domain Optical Coherence Tomography Clock-Hour, Deviation, and Thickness Maps in Detecting Photographic Retinal Nerve Fiber Layer Abnormalities