| The spectral domain OCT (SD OCT) is deemed to be the most promising OCT technology. Compared with time domain (TD) OCT, it shows much faster scan speed and higher axial revolution, and improves visualization of the intra-retinal structures in vivo more clear.In clinical use of SDOCT, we have many questions:Is there any difference between the retinal nerve fiber layer (RNFL) thicknesses measured using SDOCT and TDOCT? And whether the diagnostic power of SDOCT is better? Whether the topographic profiles of localized RNFL defects determined by SD-OCT and TD-OCT agree with that determined by fundus photography? And is the SDOCT more sensitive and accurate? How the macular ganglion cell complex (GCC) thickness changes in glaucoma patients? Whether the GCC thickness changes correlate with the changes of visual functional parameters? Is photoreceptor involved in glaucoma? About the above problems, we found few reports conducted by some overseas researchers, but they are far from solved, and no report in Chinese.In this study, we use SDOCT to measure the RNFL, GCC and photoreceptor layer thickness, and analyze the intra-retinal structural damage in glaucoma. We hope to give answers to these clinical questions, and help us understanding the pathophysiology of glaucoma and assisting clinicians in glaucoma management.Part I Retinal nerve fiber layer thickness measurement by SD-OCTPurpose1. To compare the RNFL thickness measurements in mild glaucoma, preperimetric glaucoma patients and non-glaucoma subjects between TD-OCT and SD-OCT, to assess the diagnostic values of RNFL measurements by the two types OCT.2. To evaluate the correlation and agreement between topographic profiles of localized RNFL defects determined by SD-OCT and TD-OCT with fundus photography. Methods1. Cirrus HD-OCT and Stratus OCT were used to measure the RNFL thickness of 62 eyes of 62 non-glaucoma subjects,47 eyes of 47 mild glaucoma patients, and 30 eyes of 30 preperimetric glaucoma patients. The measurements of RNFL thickness parameters, their correlation, and diagnostic value between the two types OCT was compared and evaluated. The positive rates in glaucoma patients determined by the standard normal databases of the OCT systems were calculated.2. Forty-one eyes of 41 non-glaucoma subjects and 55 eyes of 55 glaucomatous patients with localized, wedge-shaped RNFL defects identified by two glaucoma specialists in fundus photographs were enrolled in the study. The angular location and width of RNFL defects determined on the images of fundus photography, Cirrus HD-OCT and Stratus OCT were analyzed respectively using Pearson's correlation coefficient and linear regression analysis, to assess the diagnostic values of RNFL defects determined by two types OCT.Results1. The measuring values of the four quadrants and global average RNFL thickness parameters on the three groups by Cirrus HD-OCT were thinner than those by Stratus OCT with significant difference. The difference of the global average RNFL thickness between the two types OCT were 11.6±10.6μm,6.9±17.5μm and 6.0±13.1μm respectively in the non-glaucoma, preperimetric glaucoma and mild glaucoma groups. The correlation coefficients (r) of the RNFL thickness parameters between the two types OCT were 0.676-0.935 (P=0.000). Inferior and superior quadrant, global average RNFL thickness had the largest r value more than 0.9.2. The area under the receive operating characteristic curve (AROC) of global average RNFL measured by Cirrus HD-OCT and Stratus OCT on preperimetric glaucoma patients were 0.951 and 0.881 (P=0.006), and the AROC of the four quadrants RNFL thickness between the two types OCT without significant difference (P>0.05). The differences of the two OCTs'AROC of all the RNFL thickness parameters on mild glaucoma patients were all no significant (P>0.05). The AROC of the global average, inferior and superior RNFL thickness were larger than 0.87 on preperimetric glaucoma group,0.95 on mild glaucoma group.3. Based on the standard normal database of Cirrus HD-OCT and Stratus OCT systems, the positive rates in preperimetric glaucoma patients were 83.4% and 43.3%, in mild glaucoma patients were 97.9% and 95.8%.4. Seventy-five RNFL defects were identified in 55 glaucomatous eyes by two glaucoma specialists unanimously with the defect position at superior-temporal and inferior-temporal quadrants. If the RNFL thickness in the red color band of the normal database defined as the defect borderline, the sensitivity of Cirrus HD-OCT and Stratus OCT to determining RNFL defects were 88.0% and 69.3% respectively and their specificity were 92.7% and 97.6% respectively.5. The angular locations of RNFL defects by Cirrus HD-OCT and Stratus OCT were highly correlated with those by fundus photography (r=0.993,0.992, P<0.001). No significant differences were found in the defect width of RNFL between Cirrus HD-OCT or Stratus OCT and fundus photography (Cirrus HD-OCT:P=0.114; Stratus OCT:P=0.074), and the angular widths of RNFL defects by Cirrus HD-OCT and Stratus OCT were moderately correlated with those by fundus photography(r=0.420,0.432, P=0.019,0.002). The angular widths of RNFL defects by Cirrus HD-OCT was larger than that by Stratus OCT (P=0.002).Conclusions1. RNFL thickness measurements generally were thinner by Cirrus HD-OCT than by Stratus OCT in mild glaucoma, preperimetric glaucoma patients and non-glaucoma subjects, but the measurements of the two types OCT correlated well.2. The global average, superior and inferior quadrant RNFL thickness measured by both of the two types OCT, could distinguish between the mild glaucoma or preperimetric glaucoma patients and non-glaucoma subjects. The diagnostic power of Cirrus HD-OCT was higher than that of Stratus OCT.3. Both of the two types OCT could localize RNFL defects with high sensitivity and specificity. The measure value of Cirrus HD-OCT and Stratus OCT for RNFL defects showed a good diagnostic agreement with fundus photography. Part□Ganglion cell complex thickness measurement by SD-OCTPurpose1. To explore the macular GCC thickness feature in POAG patients measured with SD-OCT.2. To analyze the association between GCC, RNFL thickness and the visual function parameters, and evaluate the relationship between structural and functional damage of retina in glaucoma.Methods1. The macular GCC thickness and peripapillary RNFL thickness of 41 eyes of 41 non-glaucoma subjects and 101 eyes of 101 POAG patients were measured using RTVue-100 and Stratus OCT respectively. The measurements of the 5 GCC thickness parameters (GCC-Avg, GCC-Sup, GCC-Inf, GCC-GLV and GCC-FLV) were compared between mild glaucoma or preperimetric glaucoma patients and non-glaucoma subjects, and among the mild, advanced and end-stage glaucoma patients. The area under the receive operating characteristic curve (AROC) of the GCC thickness and RNFL thickness were calculated and compared.2. Ninety-five eyes of 95 POAG patients and 41 eyes of 41 non-glaucoma subjects were enrolled in the study. Macular GCC-Avg thickness and peripapillary average RNFL thickness were measured using RTVue-100 OCT and Cirrus HD-OCT respectively, mean deviation (MD) of visual field was examined using Humphrey VF analyzer, photopic electroretinograms were elicited by white stimuli on a white background and the amplitude of photopic negative response (PhNR) were measured. The associations between the GCC or RNFL thickness and MD or amplitude of PhNR were evaluated with linear and curvilinear regression models.Results1. There were significant differences of the 5 GCC thickness measurements between mild glaucoma or preperimetric glaucoma patients and non-glaucoma subjects (P<0.001). 2. The measurements of GCC-Avg, GCC-Sup and GCC-Inf thickness were decreased, while the measurements of GCC-FLV and GCC-GLV were increased, from mild and advanced to end-stage glaucoma with significant difference (P<0.001).3. The AROC of the 5 GCC thickness parameters (GCC-Avg, GCC-Sup, GCC-Inf, GCC-GLV and GCC-FLV) were 0.965,0.950,0.949,0.967 and 0.972 respectively. The AROC of global average RNFL thickness parameter was 0.978. There were no significant differences of the AROC between the 5 GCC thickness and RNFL thickness paramenters.4. The curvilinear regression model better described the relationship between GCC thickness and MD with coefficient of determination (R2=0.595), and the linear regression model better fit the relationship between GCC thickness and amplitude of PhNR with coefficient of determination (R2=0.437). RNFL thickness showed the similar regression models with MD and amplitude of PhNR as GCC thickness, but the coefficients of determination were higher between the RNFL thickness and MD or amplitude of PhNR (R2=0.606,0.454).Conclusions1. The macular GCC thickness measured using SDOCT decreased with the severity of glaucoma, it could well differentiate between non-glaucoma subjects and glaucomatous patients.2. Both of the GCC thickness and RNFL thickness showed a curvilinear relationship with MD and a linear relationship with amplitude of PhNR, the coefficients of determination of GCC thickness were lower than RNFL thickness.Part□Photoreceptor layer thickness measurement by SD-OCTPurpose1. To explore the feasibility and repeatability of manual measure photoreceptor layer thickness using SDOCT.2. To measure and compare photoreceptor layer thickness between glaucoma and non-glaucoma subjects using SDOCT, and explore the change of photoreceptor in glaucoma. Methods1. The macular areas of 40 eyes from 40 normal subjects were imaged by SDOCT. The outer nuclear layer (ONL) and inner and outer segments (IS/OS) layer thicknesses in fovea and parafovea (1.5 mm from the fovea) were measured by a single masked observer using an image analysis software (SigmaScan Pro version 5.0).2. Repeatability test:the measurements were repeated 3 times in a random sample of 30 normal macular images to determine the intraclass correlation coefficient (ICC), within-subject coefficient of variation (CVw) and repeatability coefficient.3. Forty-eight eyes of 48 POAG patients and 38 eyes of 38 non-glaucoma subjects were measured the photoreceptor layer thickness in fovea and parafovea using SDOCT. The measurements between glaucoma and non-glaucoma groups were compared. The association between photoreceptor layer thickness and RNFL thickness was evaluated.Results1. The ONL,IS and OS layer thickness in normal subjects were 96.1±10.5μm,24.2±2.1μm and 32.1±3.2μm respectively in fovea, and 69.2±13.1μm,22.0±2.4μm and 23.9±4.1μm respectively in parafovea.2. Repeatability test results:the ICC of ONL, IS and OS layer thickness measurement was 0.964,0.816 and 0.824 respectively, the CVw of the 3 layer thickness measurement was 3.11%,4.98% and 4.91%, and the repeatability coefficient of the 3 layer thickness measurement was 8.475,8.137 and 8.132, respectively.3. The total photoreceptor layer and the ONL thickness in the fovea were 165.9±16.7μm and 105.7±13.9μm respectively in the mild glaucoma group, which were higher than that of the non-glaucoma group (P=0.026,0.020). While the IS+OS layer thickness in the fovea were 60.4±5.6μm, which was no significant difference compared with the non-glaucoma group (P= 1.000). The total photoreceptor layer, the ONL, and the IS+OS layer thickness in the parafovea were 160.0±14.8μm,101.8±12.7μm and 58.5±5.3μm respectively in the advanced glaucoma group, which was no significant difference compared with the non-glaucoma group (P=0.751,0.350,1.000).4. The relationship between ONL in fovea and RNFL thickness in glaucoma group was best described with a second order polynomial regression model association (Y=-0.019X2+ 2.73X+10.34,R2=0.211, P=0.005).5. There were no significant differences between the glaucoma and non-glaucoma group of the ONL, IS and OS layer thickness in parafovea (P=0.410,0.445,0.198).Conclusions1. The manual measure photoreceptor layer thickness using SDOCT was feasible and repeatable for in vivo study.2. The foveal ONL thickness was increased in mild glaucomatous eyes. The curvilinear alteration of foveal ONL thickness was associated with the severity of the disease. |
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