Two precision medicine predictive tools for six malignant solid tumors: from gene-based research to clinical application.

BACKGROUND: The current study aimed to construct competing endogenous RNA (ceRNA) regulation network and develop two precision medicine predictive tools for colorectal cancer (CRC). METHODS: Differentially expressed (DE) analyses were performed between CRC tissues and normal tissues. A ceRNA regulation network was constructed based on DElncRNAs, DEmiRNAs, and DEmRNAs. RESULTS: Fifteen mRNAs (ENDOU, MFN2, FASLG, SHOC2, VEGFA, ZFPM2, HOXC6, KLK10, DDIT4, LPGAT1, BEX4, DENND5B, PHF20L1, HSP90B1, and PSPC1) were identified as prognostic biomarkers for CRC by multivariate Cox regression. Then a Fifteen-mRNA signature was developed to predict overall survival for CRC patients. Concordance indexes were 0.817, 0.838, and 0.825 for 1-, 2- and 3-year overall survival. Patients with high risk scores have worse OS compared with patients with low risk scores. CONCLUSION: The current study provided deeper understanding of prognosis-related ceRNA regulatory network for CRC. Two precision medicine predictive tools named Smart Cancer Survival Predictive System and Gene Survival Analysis Screen System were constructed for CRC. These two precision medicine predictive tools can provide valuable precious individual mortality risk prediction before surgery and improve the individualized treatment decision-making.

Two predictive precision medicine tools for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a serious threat to public health due to its poor prognosis. The current study aimed to develop and validate a prognostic nomogram to predict the overall survival of HCC patients. METHODS: The model cohort consisted of 24,991 mRNA expression data points from 348 HCC patients. The least absolute shrinkage and selection operator method (LASSO) Cox regression model was used to evaluate the prognostic mRNA biomarkers for the overall survival of HCC patients. RESULTS: Using multivariate Cox proportional regression analyses, a prognostic nomogram (named Eight-mRNA prognostic nomogram) was constructed based on the expression data of N4BP3, -ADRA2B, E2F8, MAPT, PZP, HOXD9, COL15A1, and -NDST3. The C-index of the Eight-mRNA prognostic nomogram was 0.765 (95% CI 0.724-0.806) for the overall survival in the model cohort. The Harrell's concordance-index of the Eight-mRNA prognostic nomogram was 0.715 (95% CI 0.658-0.772) in the validation cohort. The survival curves demonstrated that the HCC patients in the high risk group had a significantly poorer overall survival than the patients in the low risk group. CONCLUSION: In the current study, we have developed two convenient and efficient predictive precision medicine tools for hepatocellular carcinoma. These two predictive precision medicine tools are helpful for predicting the individual mortality risk probability and improving the personalized comprehensive treatments for HCC patients. The Smart Cancer Predictive System can be used by clicking the following URL: https://zhangzhiqiao2.shinyapps.io/Smart_cancer_predictive_system_HCC_2/. The Gene Survival Analysis Screen System is available at the following URL: https://zhangzhiqiao5.shinyapps.io/Gene_Survival_Analysis_A1001/.

Comprehensive bioinformatics analysis reveals potential lncRNA biomarkers for overall survival in patients with hepatocellular carcinoma: an on-line individual risk calculator based on TCGA cohort.

BACKGROUND: Accumulated evidences have demonstrated that long non-coding RNAs (lncRNAs) are correlated with prognosis of patients with hepatocellular carcinoma. The current study aimed to develop and validate a prognostic lncRNA signature to improve the prediction of overall survival in hepatocellular carcinoma patients. METHODS: The study cohort involved 348 hepatocellular carcinoma patients with lncRNA expression information and overall survival information. Through gene mining approach, the current study established a prognostic lncRNA signature (named LncRNA risk prediction score) for predicting the overall survival of hepatocellular carcinoma patients. RESULTS: The current study built a predictive nomogram based on ten prognostic lncRNA predictors through Cox regression analysis. In model group, the Harrell's concordance indexes of LncRNA risk prediction score were 0.811 (95% CI 0.769-0.853) for 1-year overall survival, 0.814 (95% CI 0.772-0.856) for 3-year overall survival and 0.796 (95% CI 0.754-0.838) for 5-year overall survival respectively. In validation cohort, the Harrell's concordance indexes of LncRNA risk prediction score were 0.779 (95% CI 0.737-0.821), 0.828 (95% CI 0.786-0.870) and 0.796 (95%CI 0.754-0.838) for 1-year survival, 3-year survival and 5-year survival respectively. LncRNA risk prediction score could stratify hepatocellular carcinoma patients into low risk group and high risk group. Further survival curve analysis demonstrated that the overall survival rate of high risk patients was significantly poorer than that of low risk patients (P < 0.001). CONCLUSIONS: In conclusion, the current study developed and validated a prognostic signature to predict the individual mortality risk for hepatocellular carcinoma patients. LncRNA risk prediction score is helpful to identify the patients with high mortality risk and optimize the individualized treatment decision. The web calculator can be used by click the following URL: https://zhangzhiqiao2.shinyapps.io/Smart_cancer_predictive_system_HCC_3/.

The competitive endogenous RNA regulatory network reveals potential prognostic biomarkers for overall survival in hepatocellular carcinoma.

The aim of the present study is to construct a competitive endogenous RNA (ceRNA) regulatory network by using differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in patients with hepatocellular carcinoma (HCC), and to construct a prognostic model for predicting overall survival (OS) of HCC patients. Differentially expressed lncRNAs, miRNAs, and mRNAs were explored between HCC tissues and normal liver tissues. A prognostic model was built for predicting OS of HCC patients and receiver operating characteristic curves were used to evaluate the performance of the prognostic model. There were 455 differentially expressed lncRNAs, 181 differentially expressed miRNAs, and 5035 differentially expressed mRNAs. A ceRNA regulatory network was constructed based on 43 lncRNAs, 37 miRNAs, and 105 mRNAs. Eight mRNA biomarkers (H2AFX, SQSTM1, ITM2A, PFKP, TPD52L1, ACSL4, STRN3, and CPEB3) were identified as independent risk factors by multivariate Cox regression and were used to develop a prognostic model for OS. The C-indexes in the model group were 0.776 (95% confidence interval [CI], 0.730-0.822), 0.745 (95% CI, 0.699-0.791), and 0.789 (95% CI, 0.743-0.835) for 1-, 3-, and 5-year OS, respectively. The current study revealed potential molecular biological regulation pathways and prognostic biomarkers by the ceRNA regulatory network. A prognostic model based on prognostic mRNAs in the ceRNA network might be helpful to predict the individual mortality risk for HCC patients. The individual mortality risk calculator can be used by visiting the following URL: https://zhangzhiqiao.shinyapps.io/Smart_cancer_predictive_system_HCC/.

Development and internal validation of a nine-lncRNA prognostic signature for prediction of overall survival in colorectal cancer patients.

BACKGROUND: Colorectal cancer remains a serious public health problem due to the poor prognosis. In the present study, we attempted to develop and validate a prognostic signature to predict the individual mortality risk in colorectal cancer patients. MATERIALS AND METHODS: The original study datasets were downloaded from The Cancer Genome Atlas database. The present study finally included 424 colorectal cancer patients with wholly gene expression information and overall survival information. RESULTS: A nine-lncRNA prognostic signature was built through univariate and multivariate Cox proportional regression model. Time-dependent receiver operating characteristic curves in model cohort demonstrated that the Harrell's concordance indexes of nine-lncRNA prognostic signature were 0.768 (95% CI [0.717-0.819]), 0.778 (95% CI [0.727-0.829]) and 0.870 (95% CI [0.819-0.921]) for 1-year, 3-year and 5-year overall survival respectively. In validation cohort, the Harrell's concordance indexes of nine-lncRNA prognostic signature were 0.761 (95% CI [0.710-0.812]), 0.801 (95% CI [0.750-0.852]) and 0.883 (95% CI [0.832-0.934]) for 1-year, 3-year and 5-year overall survival respectively. According to the median of nine-lncRNA prognostic signature score in model cohort, 424 CRC patients could be stratified into high risk group (n = 212) and low risk group (n = 212). Kaplan-Meier survival curves showed that the overall survival rate of high risk group was significantly lower than that of low risk group (P < 0.001). DISCUSSION: The present study developed and validated a nine-lncRNA prognostic signature for individual mortality risk assessment in colorectal cancer patients. This nine-lncRNA prognostic signature is helpful to evaluate the individual mortality risk and to improve the decision making of individualized treatments in colorectal cancer patients.

Nomogram for cirrhosis in patients with chronic hepatitis B: A simple self-assessed scale for individual risk of cirrhosis.

The aim of this retrospective study was to establish a simple self-assessed scale for individual risk of cirrhosis in patients with chronic hepatitis B. A total of 1808 consecutive patients were enrolled and analyzed. According to the results of multivariate logistic regression analysis, a simple nomogram was calculated for cirrhosis. The area under receiver operating characteristic curves (AUROCs) were calculated to compare the diagnostic accuracy of nomogram with aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based on the four factors (FIB-4), and S index. The AUROCs of nomogram for cirrhosis were 0.807 (adjusted AUROC 0.876) in model group and 0.794 (adjusted AUROC0.866) in validation group. DeLong's test and Brier Score further demonstrated that nomogram was superior to APRI, FIB-4 and S index in both model group and validation group. The patients with nomogram <0.07 could be defined as low risk group with cirrhosis prevalence lower than 4.3% (17/397). The patients with nomogram >0.52 could be defined as high risk group with cirrhosis prevalence higher than 73.0% (119/163). In conclusion, as a self-assessed style, simple, non-invasive, economical, convenient, and repeatable scale, nomogram is suitable to serve as a massive health screening tool for cirrhosis in CHB patients and further external validation is needed.

Retinal vessel diameter changes in different severities of diabetic retinopathy by SD-OCT.

PURPOSE: To evaluate retinal vessel diameters in relation to different severity grades of diabetic retinopathy (DR) using spectral-domain optical coherence tomography (SD-OCT). METHODS: Patients with varying degrees of nonproliferative DR (NPDR) underwent circular OCT scans centered on the optic nerve head using a SD-OCT. These cases were retrospectively reviewed. The presence and severity of DR was assessed using Early Treatment Diabetic Retinopathy Study protocols. The 5 largest retinal arterioles and venules were labeled and measured on OCT scans for each patient according to previously published methods. Vertical vessel inner contour diameter, vertical vessel outer contour diameter, and reflectance shadowing width were among the documented parameters. RESULTS: Of 59 eyes from 45 patients examined, 30 (50.2%) and 29 (49.8%) had mild and severe NPDR, respectively. Eyes with severe NPDR had narrower mean arteriolar vertical vessel inner diameter (87.9 ± 10.8 µm), vertical vessel outer diameter (119.1 ± 9.7 µm), and vessel shadow width (78.8 ± 10.9 µm) than eyes with mild NPDR (89.8 ± 12.1 µm, 120.9 ± 12.9 µm, 81.3 ± 15.3 µm). However, the differences were not statistically significant (p = 0.53, 0.55, 0.47). No correlation was shown between the severity of NPDR and arteriolar parameters (p = 0.31, 0.59, 0.75). Wider venular diameters were associated with increasing severity of NPDR (p<0.001, <0.001, 0.007, respectively). The association remained after multivariate adjustment for age, sex, eye, and cataract surgery (p = 0.04, 0.01, 0.007, respectively). CONCLUSIONS: Wider retinal venule diameter was significantly associated with the severity of NPDR by SD-OCT-assisted measurement. Prospective studies would be needed to evaluate whether change in retinal venule could be used as a clinical indicator of DR progression.

Subretinal fluid in eyes with active ocular toxoplasmosis observed using spectral domain optical coherence tomography.

PURPOSE: To describe the clinical finding of subretinal fluid (SRF) in the posterior pole by spectral domain optical coherence tomography (SD-OCT) in eyes with active ocular toxoplasmosis (OT). DESIGN: Retrospective case series. PARTICIPANTS: Thirty-nine eyes from 38 patients with active OT [corrected].. METHODS: Eyes with active OT which underwent SD-OCT were reviewed. SRFs in the posterior pole were further analyzed. MAIN OUTCOME MEASURES: Presence of SRF; its accompanying features, e.g. retinal necrosis, cystoid macular edema (CME), choroidal neovascularization (CNV); and longitudinal changes of SRF, including maximum height and total volume before and after treatment. RESULTS: SRF presented in 45.5% (or 15/33) of eyes with typical active OT and in 51.3% (or 20/39) of eyes with active OT. The mean maximum height and total volume of SRF were 161.0 (range: 23-478) µm and 0.47 (range: 0.005-4.12) mm3, respectively. For 12 eyes with SRF related to active retinal necrosis, SRF was observed with complete absorption after conventional anti-toxoplasmosis treatment. The mean duration for observation of SRF clearance was 33.8 (range: 7-84) days. The mean rate of SRF clearance was 0.0128 (range: 0.0002-0.0665) mm3/day. CONCLUSIONS: SRF (i.e., serous retinal detachment) is a common feature in patients with active OT when SD-OCT is performed. The majority of SRF was associated with retinal necrosis and reacted well to conventional therapy, regardless of total fluid volume. However, SRF accompanying with CME or CNV responded less favorably or remained refractory to conventional or combined intravitreal treatment, even when the SRF was small in size.

Effect of anti-VEGF treatment on choroidal thickness over time in patients with neovascular age-related macular degeneration.

PURPOSE: To evaluate change in subfoveal choroidal thickness (SCT) as measured by spectral-domain optical coherence tomography (SD-OCT) in patients with neovascular age-related macular degeneration (NVAMD) undergoing anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Patients with a diagnosis of NVAMD were retrospectively reviewed to identify those who had at least 12 months of follow-up. The SCT was manually measured from Bruch membrane to the choroid-sclera junction at baseline and last follow-up. Only cases in which the choroid was fully visible were included in quantitative analyses. The SCT measurements were correlated with other characteristics including number and duration of treatments. RESULTS: Sixty eyes of 47 patients with a follow-up of 23.8 months (SD 7.3) met study inclusion criteria, and 49 eyes of 40 patients received anti-VEGF treatment. Mean age was 83.7 years, and 52% were female. Treated eyes received a mean of 7.8 (SD 7.3) intravitreal anti-VEGF injections. The SCT at baseline was 126.7 µm (SD 50.6) for untreated and 136.2 µm (SD 57.6) for treated eyes. The SCT showed a decrease over time in both groups, with a mean rate of reduction of 6.0 µm (p<0.0002) in treated eyes and 3.6 µm (p = 0.3741) in untreated eyes. However, the change in SCT did not differ between the groups (p = 0.5113), and did not correlate with the number of re-treatments (p = 0.552), visual acuity at baseline (p = 0.618), or change in visual acuity over time (p = 0.429). CONCLUSIONS: Although choroidal thickness decreased over time in eyes with NVAMD, anti-VEGF therapy did not appear to accelerate or otherwise alter this decline.

Evaluation of cystoid change phenotypes in ocular toxoplasmosis using optical coherence tomography.

PURPOSE: To present unique cystoid changes occurring in patients with ocular toxoplasmosis observed in spectral domain optical coherence tomography (OCT). METHODS: Forty-six patients (80 eyes) with a diagnosis of ocular toxoplasmosis, who underwent volume OCT examination between January 2005 and October 2012, were retrospectively collected. Review of clinical examination findings, fundus photographs, fluorescein angiograms (FA) and OCT image sets obtained at initial visits and follow-up. Qualitative and quantitative analyses of cystoid space phenotypes visualized using OCT. RESULTS: Of the 80 eyes included, 17 eyes (15 patients) demonstrated cystoid changes in the macula on OCT. Six eyes (7.5%) had cystoid macular edema (CME), 2 eyes (2.5%) had huge outer retinal cystoid space (HORC), 12 eyes (15%) had cystoid degeneration and additional 3 eyes (3.75%) had outer retinal tubulation due to age related macular degeneration. In one eye with HORC, the lesion was seen in the photoreceptor outer segment, accompanied by photoreceptor elongation and splitting. Three eyes presented with paravascular cystoid degeneration in the inner retina without other macular OCT abnormality. CONCLUSIONS: In this study, different phenotypes of cystoid spaces seen in eyes with ocular toxoplasmosis using spectral domain OCT (SD-OCT) were demonstrated. CME presented as an uncommon feature, consistently with previous findings. Identification of rare morphological cystoid features (HORC with/without photoreceptor enlongation or splitting) on clinical examination had provided evidence to previous experimental models, which may also expand the clinical spectrum of the disease. Cystoid degeneration in the inner retina next to the retinal vessels in otherwise "normal" looking macula was observed, which may suggest more often clinical evaluation for those patients. Further studies are needed to verify the relevance of cystoid features seen on SD-OCT in assisting with the diagnosis and management of ocular toxoplasmosis.

Clinical outcomes after switching treatment from intravitreal ranibizumab to aflibercept in neovascular age-related macular degeneration.

PURPOSE: To describe the treatment response to aflibercept in patients with exudative age-related macular degeneration that showed insufficient or diminishing treatment effects under ranibizumab. METHODS: From December 2012 till June 2013 all patients receiving intravitreal injections of aflibercept after previous treatment with ranibizumab were collected in a database and retrospectively reviewed. Clinical data such as visual acuity or central subfield retinal thickness on optical coherence tomography (OCT) scans were analyzed for the time frame before, during, and shortly after the aflibercept injections. Of particular interest was the comparison of clinical features under ongoing ranibizumab treatment to the time during aflibercept treatment. RESULTS: Seventy-one eyes of 65 patients were included in the study. All eyes had previous ranibizumab injections in their medical history, the average number of which was nine (range 3-43). For the total group the mean visual acuity (VA) before the first ranibizumab injection was 0.54 logMAR, and after the last ranibizumab injection was 0.57 logMAR. Mean VA changed from 0.47 logMAR before the first aflibercept injection to 0.25 logMAR after the last aflibercept injection. Central subfield retinal thickness (CSRT) on OCT changed from a mean of 417.28 µm to 349.52 µm under ranibizumab treatment and from 338.76 µm to 272.00 µm under aflibercept treatment. Interestingly, 33 % of cases that did not show a functional improvement under ranibizumab therapy gained visual acuity after aflibercept treatment. CONCLUSION: Aflibercept appears to be an effective choice for patients with neovascular age-related macular degeneration who were resistant to previous therapy of ranibizumab. The longevity of this effect still remains questionable.

The retinal disease screening study: retrospective comparison of nonmydriatic fundus photography and three-dimensional optical coherence tomography for detection of retinal irregularities.

PURPOSE: To determine the sensitivity of three-dimensional optical coherence tomography (3D-OCT) versus single field nonmydriatic fundus photography (FP) for detection of a variety of retinal abnormalities. METHODS: Images from consecutive patients in a retina clinic undergoing simultaneous 3D-OCT (512 × 128) and single, foveal nonmydriatic 45° color fundus imaging with 3D-OCT-1000 in a 4 month-period were retrospectively collected. Findings from each modality were graded independently by two graders as present, questionable, or absent. Irregularities were separated into three categories for intermodality comparisons: epiretinal, retinal/subretinal, and RPE/choroidal irregularities. The approximate location of findings in relation to the 3D-OCT field was noted as in field and out of field. Findings from both modalities were combined to form the gold standard for comparison for each modality. RESULTS: Five hundred and one sets of 3D-OCT scans and fundus images of 395 eyes of 223 patients were found in the study period, of which, 474 unique visits were included. Ninety-six percent of the scans had abnormal findings. Twenty-six fundus images (5.5%) were ungradable. 3D-OCT identified some abnormality in 25/26 (96.2%) of the ungradable fundus images. For overall detection of a variety of retinal irregularities or irregularity of each category (epiretinal, intraretinal, or RPE/choroidal irregularity), 3D-OCT was found to be more sensitive than that of nonmydriatic color fundus images. When single specific feature was speculated, 3D-OCT demonstrated various detection abilities: higher than FP for abnormal retinal thickness (or intraretinal hyporeflective features); similar as FP for RPE atrophy; however, lower for pigment migration (or intraretinal hemorrhage). CONCLUSIONS: In this study, sensitivities of 3D-OCT were higher than nonmydriatic fundus images for overall detection of retinal abnormalities or irregularities in each category. 3D-OCT demonstrated good ability to detect most features; however, with limitation to intraretinal hemorrhage and pigment migration. It is likely that OCT will be added to photography screening for chorioretinal diseases in the near future.

Different phenotypes of the appearance of the outer plexiform layer on optical coherence tomography.

PURPOSE: To present a selected case series of different phenotypes of the normal outer plexiform layer (OPL) visualized by optical coherence tomography (OCT). METHODS: Five cases were selected to represent the spectrum of appearances of the OPL in this case series. Categorical descriptions of each manifestation were then developed. Additional SD-OCT scans were obtained from a normal volunteer to further support the hypothesis. RESULTS: The inner one-third of the OPL typically appears hyperreflective on OCT, while the outer two-thirds (Henle fiber layer) may have a more varied appearance. Six different phenotypes of Henle fiber layer reflectivity were noted in this series, and classified as: bright, columnar, dentate, delimited, indistinct, and dark. The brightness of the Henle fiber layer appears to depend on the geometric angle between the OCT light beam and the axonal fibers in this portion of the OPL. This angle appears to be a function of the natural orientation of the Henle fiber layer tissue (θN), the existence of subretinal pathology that alters the angle of the neurosensory retina (θ(P)), and the tilt angle of the tissue on the B-scan (θ(T)) due to decentered OCT acquisition. CONCLUSIONS: Since accurate interpretation of the OPL/ONL boundary is of vital importance to study the thickness of ONL, location of cystoid lesions, hyperreflective crescents over drusen, et al., our case series may aid better understanding of the OPL appearance in SD-OCT. In the absence of clear delineation, it may be most correct to refer to indistinct OPL and ONL together as the photoreceptor nuclear axonal complex (PNAC).

Evaluation of the axial location of cystoid spaces in retinal vein occlusion using optical coherence tomography.

PURPOSE: To analyze the axial distribution of intraretinal cystoid changes in patients with retinal vein occlusion (RVO), incorporating a new hypothesis about the optical coherence tomographic boundary between the outer nuclear layer and the outer plexiform layer. METHODS: Data were collected from patients with RVO who underwent spectral domain coherence tomography imaging. For each image set, certified graders evaluated each retinal layer for cystoid macular edema, defined as hyporeflective intraretinal cystoid spaces. Subretinal fluid, if present, was also noted. RESULTS: Forty-eight eyes were evaluated (24 branch RVO, 18 central RVO, 6 hemiretinal vein occlusion). Cystoid macular edema was present in 30.8% of eyes in outer nuclear layer, 77.9 % in outer plexiform layer, 77.9 % in inner nuclear layer, 36.9 % in inner plexiform layer, 48.8 % in ganglion cell layer, and 4.9% in nerve fiber layer. Subretinal fluid was assessed as present in 23.8% of patients. The presence of subretinal fluid correlated most strongly with cystoid changes in the outer nuclear layer (r = 0.514, P = 0.001) but was not significantly correlated with these changes in the superficial retina. CONCLUSION: Use of spectral domain coherence tomography allows precise characterization of the axial location of cystoid spaces in RVO and highlights the frequency of fluid accumulation in the outer plexiform layer and inner nuclear layer. Using updated definitions, cystoid macular edema seems to occur less frequently in the outer nuclear layer, but when it does so, it is often associated with subretinal fluid. Future longitudinal studies, documenting the axial progression of such changes, and their response to treatment, may be of clinical relevance as pharmacotherapeutic options evolve.

Assessment of differential pharmacodynamic effects using optical coherence tomography in neovascular age-related macular degeneration.

PURPOSE: To use novel OCT parameters in assessing the differential pharmacodynamic effects of bevacizumab (Avastin; Genentech, South San Francisco, CA), pegaptanib (Macugen; OSI Pharmaceuticals, New York, NY), and verteporfin photodynamic therapy (PDT; Novartis, Basel, Switzerland) in a recently completed phase III/IV clinical trial. METHODS: Data from 122 patients participating in the Avastin (Bevacizumab) for Choroidal Neovascularization (ABC) trial, were evaluated. OCT scans were analyzed with custom software. Changes in the volume of the neurosensory retina, amount of subretinal fluid (SRF), pigment epithelium detachment (PED), and subretinal tissue (SRT), were calculated over the 54-week trial period. RESULTS: Reductions in retinal edema were more than twice as great from bevacizumab as from pegaptanib (-0.82 mm³ vs. -0.31 mm³), whereas SRF reduction was more than three times greater (-0.54 mm³ vs. -0.15 mm³. Both bevacizumab and pegaptanib led to rapid reductions in SRT; however, in those receiving pegaptanib, these improvements were not maintained (at week 54, -0.22 mm³ vs. +0.18 mm³). Acute increases in SRF were seen 1 week after PDT (+0.36 mm³) and, across all treatment groups, PED volume tended to remain unchanged or to regress only slowly. CONCLUSIONS: In clinical trials, quantitative OCT subanalysis increases the amount of clinically useful information that can be obtained from OCT images. In the emerging era of neovascular AMD therapeutics, the capacity of OCT to provide such detailed pharmacodynamic information in a noninvasive manner is likely to attain increased importance. In future comparative studies, evaluation of SRT may highlight differential effects on vascular proliferation, whereas measurement of PED volume may be useful for the estimation of retinal and subretinal pigment epithelium (RPE) therapeutic penetration. (ClinicalTrials.gov number, ISRCTN83325075.).

Clinical significance of B-scan averaging with SD-OCT.

Averaging multiple scans is a potential advantage of optical coherence tomography. The authors evaluate the qualitative benefits of B-scan averaging on the visualization of outer retinal structures. A retrospective analysis was performed on Cirrus OCT (Carl Zeiss Meditec, Dublin, CA) B-scans from 1 eye of 35 patients referred to the imaging unit who underwent three types of scan acquisitions: no averaging, 4× averaging, and 20× averaging. Masked assessment of quality was made using a qualitative scale of 0 (worst) to 3 according to the ability to identify structure, brightness, and continuity. Quality scores consistently improved with 4× averaging, but improved only slightly further with 20×. Averaging appeared to have a statistically significant beneficial effect for the assessment of the external limiting membrane and outer nuclear layer (P < .05), with no significant benefit for visualization of the retinal pigment epithelium and inner segment/outer segment junction. The benefits of oversampling or averaging B-scans for visualizing outer retinal substructures are apparent even when averaging relatively few frames. These findings may be helpful when designing acquisition protocols in clinical trials and clinical practice.

Simple estimation of clinically relevant lesion volumes using spectral domain-optical coherence tomography in neovascular age-related macular degeneration.

PURPOSE: To evaluate simple methods of estimating the volume of clinically relevant features in neovascular age-related macular degeneration (NVAMD) using spectral domain-optical coherence tomography (SD-OCT). METHODS: Using a database of NVAMD cases imaged with macular cube (512 A-scans × 128 B-scans) SD-OCT scans, the authors retrospectively selected visits where cystoid macular edema (CME), subretinal fluid (SRF), or pigment epithelial detachments (PEDs) were evident. Patients with single visits were analyzed in the cross-sectional analysis (CSA) and those with a baseline visit and three or more follow-up visits in the longitudinal analysis (LA). The volume of each feature was measured by manual grading using validated grading software. Simplified measurements for each feature included: number of B-scans or A-scans involved and maximum height. Automated measurements of total macular volume and foveal central subfield were also collected from each machine. Correlations were performed between the volumes measured with 3D-OCTOR, automated measurements, and the simplified measures. RESULTS: Forty-five visits for 25 patients were included in this study: 26 cube scans from 26 eyes of 25 patients in the CSA and 24 scans from 5 eyes of 5 patients in the LA. The simplified measures that correlated best with manual grading in the CSA group were maximum lesion height for CME (r² value = 0.96) and B-scan count for SRF and PED volume (r² values of 0.88 and 0.70). In the LA group, intervisit differences were correlated. Change in B-scan count correlated well with change in SRF volume (r² = 0.97), whereas change in maximum height correlated with change in CME and PED volume (r² = 0.98 and 0.43, respectively). CONCLUSIONS: These data suggest that simplified estimators of some NVAMD lesion volumes exist and are accessible by clinicians without the need for specialized software or time-consuming manual segmentation. These simple approaches could enhance quantitative disease monitoring strategies in clinical trials and clinical practice.

Acute severe visual decrease after photodynamic therapy with verteporfin: spectral-domain OCT features.

In this report, spectral-domain optical coherence tomography (OCT) was used to characterize the acute morphologic alterations that occur when photodynamic therapy with verteporfin results in an acute severe visual decrease. The clinical and imaging records of a patient with neovascular age-related macular degeneration who suffered this complication were reviewed. Using spectral-domain OCT, two relatively distinct subretinal fluid compartments were visualized: a sparsely hyperreflective pocket of subretinal fluid overlying the fibrovascular pigment epithelial detachment, consistent with fibrinous exudation, and a more homogeneously hyporeflective compartment at the periphery of the choroidal neovascular lesion, consistent with serous exudation. The higher axial resolution, and greater sensitivity, of spectral-domain OCT allows improved visualization of the subretinal space. As experience with spectral-domain OCT grows, new parameters will emerge-such as those related to subretinal fluid-that will facilitate improvements in both the qualitative and quantitative evaluation of macular disease.

[Determination of five hormone drug residues in fish tissue by high performance liquid chromatography with gel permeation chromatographic clean-up].

A method was developed for the determination of five hormone residues in fish tissue by high performance liquid chromatography (HPLC) with gel permeation chromatographic (GPC) clean-up. The sample was extracted with ethyl acetate-methanol (8:2, v/v). The extract was cleaned-up on a Pharmadex LH-20 gel permeation column (450 mm x 15 mm) and eluted with methanol-ethyl acetate-acetic acid (800:200:2, v/v/v). The analysis was performed on an Agilent TC-C18 column (250 mm x 4. 6 mm, 5 microm) using acetonitrile-water (45:55, v/v) as the mobile phase at a flow rate of 1.2 mL/min and the detection wavelengths were set at 222 nm and 245 nm. All of the 5 hormone residues had good linear relationships (r > 0.999) in the range of 0.05-2.5 mg/L. The limits of detection (LOD) were from 10 to 24 microg/kg. The average recoveries for all the five hormone residues were from 60.1% to 89.0%, with relative standard deviations (RSDs) from 2.0% to 7.4%. The method is simple, rapid, and can be applied for the analysis of the five hormone residues in fish tissue.