Trastuzumab in combination with paclitaxel enhances antitumor activity by promoting apoptosis in human epidermal growth factor receptor 2-positive trastuzumab-resistant gastric cancer xenograft models.

Trastuzumab, a humanized anti-human epidermal growth factor receptor 2 antibody drug, is the first-line therapy for human epidermal growth factor receptor 2-positive breast and gastric cancer. For breast cancer, the benefit of continuous treatment with trastuzumab after it becomes refractory to first-line therapy has been demonstrated. However, it is unclear whether trastuzumab can show similar efficacy as a second-line treatment for gastric cancer. Here, we report that trastuzumab in combination with paclitaxel exhibits increased antitumor efficacy even for trastuzumab-resistant xenografted tumors. We derived the trastuzumab-resistant models from previously established human epidermal growth factor receptor 2-positive gastric cancer patient-derived cells. Human epidermal growth factor receptor 2 expression, PIK3CA mutation, and phosphatase and tensin homolog expression in these resistant models was equivalent to those in the trastuzumab-sensitive parental model, whereas cyclin-dependent kinase inhibitors, such as p16, p15, and p21, were downregulated. Trastuzumab in combination with paclitaxel enhanced antitumor activity in both the sensitive and resistant models. In the trastuzumab-sensitive model, the combination of trastuzumab and paclitaxel resulted in suppression of the AKT-p27-retinoblastoma protein pathway and induction of apoptosis. Although this combination did not suppress retinoblastoma protein phosphorylation in the trastuzumab-resistant model, it did markedly decrease epidermal growth factor receptor and human epidermal growth factor receptor 2 phosphorylation and further enhance paclitaxel-mediated apoptosis. These results suggested that trastuzumab in combination with paclitaxel can still exert more potent antitumor efficacy than each agent alone in trastuzumab-resistant models, providing evidence that trastuzumab remains beneficial in the treatment of trastuzumab-resistant tumors.

Investigating the structure-function relationship using Goldmann V standard automated perimetry where glaucomatous damage is advanced.

PURPOSE: To investigate if the structure-function relationship between circumpapillary retinal nerve fibre layer (cpRNFL) thickness and visual field (VF) thresholds is stronger when using the Goldmann V target rather than the Goldman III target where glaucomatous damage is advanced. METHODS: Optical coherence tomography (OCT) and VF (Humphrey Field Analyzer 24-2 or 30-2) measurements with Goldmann III (SITA standard) and V (full-threshold) targets were carried out in 51 eyes of 51 patients with primary open angle glaucoma. The relationship between cpRNFL thicknesses in supero- and infero-temporal sectors, and VF sensitivity with the Goldmann III or V target was investigated. RESULT: Visual field sensitivities (dB) both with the Goldmann III target and Goldmann V target showed a floor effect in the structure-function relationship against cpRNFL thickness, at approximately 60 µm. There was no significant relationship between visual field sensitivity measured with the Goldmann V target (dB scale: p = 0.12, 1/Lambert scale: p = 0.40; linear mixed models) and cpRNFL thickness, when corresponding visual field sensitivity, measured with the Goldmann III target, was <20 dB. CONCLUSION: There was no improvement in the structure-function relationship using the Goldmann V target (full-threshold), compared to using the Goldmann III target (SITA standard), where glaucomatous damage was advanced.

Impact of bevacizumab in combination with erlotinib on EGFR-mutated non-small cell lung cancer xenograft models with T790M mutation or MET amplification.

Erlotinib (ERL), an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, shows notable efficacy against non-small cell lung cancer (NSCLC) harboring EGFR mutations. Bevacizumab (BEV), a humanized monoclonal antibody to vascular endothelial cell growth factor (VEGF), in combination with ERL (BEV+ERL) significantly extended progression-free survival in patients with EGFR-mutated NSCLC compared with ERL alone. However, the efficacy of BEV+ERL against EGFR-mutated NSCLC harboring T790M mutation or MET amplification, is unclear. Here, we examined the antitumor activity of BEV+ERL in four xenograft models of EGFR-mutated NSCLC (three harboring ERL resistance mutations). In the HCC827 models (exon 19 deletion: DEL), ERL significantly inhibited tumor growth by blocking EGFR signal transduction. Although there was no difference between ERL and BEV+ERL in maximum tumor growth inhibition, BEV+ERL significantly suppressed tumor regrowth during a drug-cessation period. In the HCC827-EPR model (DEL+T790M) and HCC827-vTR model (DEL+MET amplification), ERL reduced EGFR signal transduction and showed less pronounced but still significant tumor growth inhibition than in the HCC827 model. In these models, tumor growth inhibition was significantly stronger with BEV+ERL than with each single agent. In the NCI-H1975 model (L858R+T790M), ERL did not inhibit growth or EGFR signal transduction, and BEV+ERL did not inhibit growth more than BEV. BEV alone significantly decreased microvessel density in each tumor. In conclusion, addition of BEV to ERL did not enhance antitumor activity in primarily ERL-resistant tumors with T790M mutation; however, BEV+ERL enhanced antitumor activity in T790M mutation- or MET amplification-positive tumors as long as their growth remained significantly suppressed by ERL.

Biomarkers for antitumor activity of bevacizumab in gastric cancer models.

BACKGROUND: Bevacizumab is a humanized monoclonal antibody to human vascular endothelial cell growth factor (VEGF) and has been used for many types of cancers such as colorectal cancer, non-small cell lung cancer, breast cancer, and glioblastoma. Bevacizumab might be effective against gastric cancer, because VEGF has been reported to be involved in the development of gastric cancer as well as other cancers. On the other hand, there are no established biomarkers to predict the bevacizumab efficacy in spite of clinical needs. Therefore, we tried to identify the predictive markers for efficacy of bevacizumab in gastric cancer patients by using bevacizumab-sensitive and insensitive tumor models. METHODS: Nine human gastric and two colorectal cancer mouse xenografts were examined for their sensitivity to bevacizumab. We examined expression levels of angiogenic factors by ELISA, bioactivity of VEGF by phosphorylation of VEGFR2 in HUVEC after addition of tumor homogenate, tumor microvessel density by CD31-immunostaining, and polymorphisms of the VEGF gene by HybriProbe™ assay. RESULTS: Of the 9 human gastric cancer xenograft models used, GXF97, MKN-45, MKN-28, 4-1ST, SC-08-JCK, and SC-09-JCK were bevacizumab-sensitive, whereas SCH, SC-10-JCK, and NCI-N87 were insensitive. The sensitivity of the gastric cancer model to bevacizumab was not related to histological type or HER2 status. All tumors with high levels of VEGF were bevacizumab-sensitive except for one, SC-10-JCK, which had high levels of VEGF. The reason for the refractoriness was non-bioactivity on the phosphorylation of VEGFR2 and micro-vessel formation of VEGF, but was not explained by the VEGF allele or VEGF165b. We also examined the expression levels of other angiogenic factors in the 11 gastrointestinal tumor tissues. In the refractory models including SC-10-JCK, tumor levels of another angiogenic factor, bFGF, were relatively high. The VEGF/bFGF ratio correlated more closely with sensitivity to bevacizumab than with the VEGF level. CONCLUSIONS: VEGF levels and VEGF/bFGF ratios in tumors were related to bevacizumab sensitivity of the xenografts tested. Further clinical investigation into useful predictive markers for bevacizumab sensitivity is warranted.

Relationship between vision-related quality of life and different types of existing visual fields in Japanese patients.

To investigate the vision-related quality of life (VRQOL) in relation to the type of existing visual field (EVF) in the presence of visual field defect. We evaluated the VRQOL of 95 patients by using Visual Function Questionnaire-25 (NEI VFQ-25). Patients fulfilled the following criteria: (1) they underwent a Goldmann perimetry (GP) test within 3 months of the initial visit, (2) the results of the GP test could be classified into three categories, and (3) the best-corrected decimal visual acuity (VA) was ≤0.3. The EVF was assessed by composite measurement of both eyes for the V-4e or I-4e isopters, as obtained using the GP test. We compared the VFQ-25 scores between three groups: (1) the "center and peripheral" group in which the EVF of the V-4e area was >30º and the I-4e area was <30º, (2) the "central VF" group in which the EVF of the V-4e area was <20º, and (3) the "central VF loss" group in which the central scotoma was >5º and the EVF of the V-4e area was >30º in peripheral vision. There were significant differences between the three groups (P = 0.02, ANOVA). The total score of the "central VF loss" group was significantly lower than those of the "center and peripheral" and "central VF" groups. The central vision influenced the VRQOL to a greater extent than peripheral vision.

Association between changes in visual acuity and vision-related quality of life in Japanese patients with low vision.

PURPOSE: To investigate the association between vision-related quality of life (VRQOL) and changes in visual acuity (VA). METHODS: We examined the VA in 100 patients for > 1 year and evaluated the degree of its impact on VRQOL using the National Eye Institute Visual Function (VF) Questionnaire (VFQ-25; Japanese version). Before determining VFQ-25, we monitored the changes in VA in these patients for 1 year and classified them into the following two groups depending on VA changes. Patients exhibiting a decline of > 3 steps in VA, as assessed by the logarithm of the minimum angle of resolution scale, were placed in the 'decline' group (47.0%) and patients exhibiting no change in VA were placed in the 'no change' group (53.0%). We compared the VFQ-25 scores between both groups in all patients with glaucoma (GLA) and macular degeneration (MD). RESULTS: The total score of the decline was 34.9 ± 13.6 and that of the no change group was 44.6 ± 13.9: the difference in the scores between both groups was statistically significant (p = 0.006). Similar results were obtained for patients with GLA and MD (p = 0.007 and 0.003, respectively). CONCLUSION: VRQOL differed between patients with constant VA and those with reduced VA, even though VA values were equal at a certain time point.

Bevacizumab improves the delivery and efficacy of paclitaxel.

It has been reported that bevacizumab in combination with paclitaxel significantly prolongs progression-free survival compared with paclitaxel alone in the initial treatment for metastatic breast cancer. To understand how bevacizumab enhances the efficacy of paclitaxel, we investigated the mechanism in a MX-1 human breast cancer xenograft model. The antitumor activity of bevacizumab at 5 mg/kg in combination with paclitaxel at 20 or 30 mg/kg was significantly higher than that of either agent alone. First, we measured the paclitaxel concentration in tumor to see whether bevacizumab enhances the activity by increasing the tumor concentration of paclitaxel. When given in combination with bevacizumab, the levels of paclitaxel in the tumor increased. Paclitaxel at 30 mg/kg with bevacizumab showed a similar tumor concentration as paclitaxel alone at either 60 or 100 mg/kg, with a similar degree of tumor growth inhibition. In contrast, no remarkable differences in paclitaxel concentration in the plasma or liver were observed between the paclitaxel monotherapy group and the paclitaxel plus bevacizumab group. An increase in paclitaxel concentration by bevacizumab was also found in another model, A549. In the same MX-1 model, vascular permeability in the tumor was significantly decreased by treatment with bevacizumab. There was no difference in microvessel density between the bevacizumab alone group and the combination group. Results suggest that the synergistic antitumor activity of paclitaxel and bevacizumab in combination may be a result of the increase in paclitaxel concentration in tumor resulting from the downregulation of vascular permeability when co-administered with bevacizumab.

Improving the Structure-Function Relationship in Glaucomatous Visual Fields by Using a Deep Learning-Based Noise Reduction Approach.

PURPOSE: To investigate whether processing visual field (VF) measurements using a variational autoencoder (VAE) improves the structure-function relationship in glaucoma. DESIGN: Cross-sectional study. PARTICIPANTS: The training data consisted of 82 433 VF measurements from 16 836 eyes. The testing dataset consisted of 117 eyes of 75 patients with open-angle glaucoma. METHODS: A VAE model to reconstruct the threshold of VF was developed using the training dataset. OCT and VF (Humphrey Field Analyzer 24-2, Swedish interactive threshold algorithm standard) measurements were carried out for all eyes in the testing dataset. Visual fields in the testing dataset then were reconstructed using the trained VAE. The structure-function relationship between the circumpapillary retinal nerve fiber layer (cpRNFL) thickness and VF sensitivity was investigated in each of twelve 30° segments of the optic disc (3 nasal sectors were merged). Similarly, the structure-function relationship was investigated using the VAE-reconstructed VF. MAIN OUTCOME MEASURES: Structure-function relationship. RESULTS: The corrected Akaike information criterion values with threshold were found to be smaller than the threshold reconstructed with the VAE (thresholdVAE) in 9 of 10 sectors. A significant relationship was found between threshold and cpRNFL thickness in 6 of 10 sectors, whereas it was significant in 9 of 10 sectors with thresholdVAE. CONCLUSIONS: Applying VAE to VF data results in an improved structure-function relationship.

Relationship between novel intraocular pressure measurement from Corvis ST and central corneal thickness and corneal hysteresis.

AIMS: Corvis ST (CST) yields biomechanical corrected IOP (bIOP) which is purported to be less dependent on biomechanical properties. In our accompanied paper, it was suggested that the repeatability of bIOP is high. The purpose of the current study was to assess the relationship between intraocular pressure (IOP) measured with CST and central corneal thickness (CCT) and corneal hysteresis (CH), in comparison with IOP measured with Goldmann applanation tonometry (GAT) and the ocular response analyzer (ORA). METHODS: A total of 141 eyes from 141 subjects (35 healthy eyes and 106 glaucomatous eyes) underwent IOP measurements with GAT, CST and ORA. The relationships between IOP measurements (ORA-IOPg, ORA-IOPcc, CST-bIOP and GAT IOP) and biomechanical properties (CCT, CH and corneal resistance factor (CRF)) were analysed using the linear regression analysis. RESULTS: IOPg, IOPcc and GAT IOP were significantly associated with CCT (p<0.001), whereas bIOP was not significantly associated with CCT (p=0.19). IOPg, bIOP and GAT IOP were significantly associated with CH (IOPg: p<0.001; bIOP: p<0.001; GAT IOP: p=0.0054), whereas IOPcc was not significantly associated with CH (p=0.18). All of IOP records were associated with CRF (p<0.001). CONCLUSION: The bIOP measurement from CST is independent from CCT, but dependent on CH and CRF.

Comparing Structure-Function Relationships Based on Drasdo's and Sjöstrand's Retinal Ganglion Cell Displacement Models.

Purpose: To compare structure-function relationships based on the Drasdo and Sjöstrand retinal ganglion cell displacement models. Methods: Single eyes from 305 patients with glaucoma and 55 heathy participants were included in this multicenter, cross-sectional study. The ganglion cell and inner plexiform layer (GCIPL) thickness was measured using spectral domain optical coherence tomography. Visual field measurements were performed using the Humphrey 10-2 test. All A-scan pixels (128 × 512 pixels) were allocated to the closest 10-2 location with both displacement models using degree and millimeter scales. Structure-function relationships were investigated between GCIPL thickness and corresponding visual sensitivity in nonlong (160 eyes) and long (200 eyes) axial length (AL) groups. Results: In both the nonlong and long AL groups, compared with the no-displacement model, both the Drasdo and the Sjöstrand models showed that the structure-function relationship around the fovea improved (P < 0.05). The magnitude of improvement in the area was either comparable between the model or was larger for the Drasdo model than the Sjöstrand model (P < 0.05). Meanwhile, structure-function relationships outside the innermost retinal region that were based on the Drasdo and Sjöstrand models were comparable to or were even worse than (in the case of the Drasdo model) those obtained using the no-displacement model. Conclusions: Structure-function relationships evaluated based on both the Drasdo and Sjöstrand models significantly improved around the fovea, particularly when using the Drasdo model. This was not the case in other areas.

Antitumor activity of bevacizumab in combination with capecitabine and oxaliplatin in human colorectal cancer xenograft models.

To understand the mechanisms of the effects of combination treatments, we established animal models showing antitumor activity of bevacizumab as a monotherapy and in combination with capecitabine or capecitabine and oxaliplatin and measured thymidine phosphorylase (TP) and vascular endothelial growth factor (VEGF) levels. Tumor-inoculated nude mice were treated with bevacizumab, capecitabine, and oxaliplatin, alone or in combination, after tumor growth was confirmed and volume and microvessel density (MVD) in tumors were evaluated. Levels of TP and VEGF in the tumor were examined by ELISA. Bevacizumab showed significant antitumor activity as a monotherapy in three xenograft models (COL-16-JCK, COLO 205 and CXF280). The MVD in tumor tissues treated with bevacizumab was lower than that of the control. Antitumor activity of bevacizumab in combination with capecitabine was significantly higher than that of each agent alone (COL-16-JCK, COLO 205). Furthermore, the antitumor activity of bevacizumab in combination with capecitabine + oxaliplatin was significantly superior to that of capecitabine + oxaliplatin (COL-16-JCK). TP and VEGF levels were not increased by bevacizumab or capecitabine, respectively, suggesting there are other potentially efficacious mechanisms involved. In the present study we established human colorectal cancer xenograft models which reflect the efficacy of clinical combination therapies, capecitabine + bevacizumab and capecitabine + oxaliplatin + bevacizumab. We will further investigate the mechanisms of the combination therapies using these models.

Sustained effect of continuous treatment with bevacizumab following bevacizumab in combination with chemotherapy in a human ovarian clear cell carcinoma xenograft model.

Although bevacizumab maintenance following bevacizumab in combination with chemotherapy has demonstrated significant prolongation of progression-free survival in clinical studies in patients with ovarian cancer, the majority of the cancer cases in the study were of the serous histotype; therefore, data regarding clear cell carcinoma is limited. Furthermore, the efficacy of bevacizumab beyond progression has not yet been demonstrated in ovarian cancer. A xenograft model using the human ovarian clear cell carcinoma cell line RMG-I was used to investigate the antitumor effects and the mechanisms of bevacizumab in maintenance treatment and bevacizumab when administered beyond disease progression. In the RMG-I model, bevacizumab maintenance following bevacizumab in combination with paclitaxel exhibited increased tumor suppression, compared with its absence, and inhibited the increase of microvessel density (MVD) in tumors. Following disease progression during bevacizumab maintenance, continued bevacizumab treatment in combination with PEGylated liposomal doxorubicin as a secondary chemotherapeutic agent had increased efficacy, compared with PEGylated liposomal doxorubicin alone, and resulted in lower MVD accompanied with lower levels of insulin-like growth factor binding protein-3, which is reported to have angiogenic activity. Continuous suppression of angiogenesis by bevacizumab may contribute to the superior efficacy of bevacizumab maintenance and bevacizumab beyond progression in ovarian cancer.

Repeatability of the Novel Intraocular Pressure Measurement From Corvis ST.

PURPOSE: To assess the repeatability of intraocular pressure (IOP) measured with the Corvis ST (CST) and the Ocular Response Analyzer (ORA). METHODS: A total of 141 eyes from 141 subjects were studied, including 35 healthy eyes and 106 glaucomatous eyes. All subjects underwent IOP evaluations with Goldmann applanation tonometer, CST, and ORA. With CST, biomechanical corrected IOP (bIOP) was calculated; bIOP is purported to be less dependent on biomechanical properties. For ORA, corneal-compensated intraocular pressure (IOPcc) and Goldmann-correlated IOP (IOPg) were derived. The repeatability of the various IOP values was assessed using the coefficient of variance (CV) and the intraclass correlation coefficient (ICC). RESULTS: The CV with bIOP (5.5 ± 3.1: mean ± standard deviation) was significantly smaller than the CVs measured with IOPg (7.3 ± 4.3) and IOPcc (7.2 ± 4.4). ICC values were 0.90, 0.80, and 0.86 with IOPg, IOPcc, and bIOP, respectively. CONCLUSIONS: The bIOP showed a better prevision and repeatability for IOP measurement. TRANSLATIONAL RELEVANCE: The bIOP measurement from CST had a better reproducible than IOPcc measurement from ORA.

Relationship between the Vertical Asymmetry of the Posterior Pole of the Eye and the Visual Field Damage in Glaucomatous Eyes.

PURPOSE: This study investigated the relationship between the shape of the posterior pole of the eye and the vertical asymmetry of visual field (VF) damage in glaucomatous eyes. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 83 eyes of 43 patients with open-angle glaucoma. METHODS: The VF was measured using the Humphrey 24-2 or 30-2 Swedish Interactive Thresholding Algorithm (SITA) standard. The vertical asymmetry of VF damage was defined as the difference between the mean total deviation (mTD) values of the superior and inferior hemi-retinas. This difference was calculated for the hemifield, central, middle, and peripheral areas. A vertical cross-sectional image of the macula was obtained, and the magnitudes of superior and inferior retinal tilt (RT) were calculated as the difference between the lower margins of the retinal pigment epithelium (RPE) at the fovea and at a location 2 mm superior or inferior to the RPE. The RT asymmetry was defined as the difference between the inferior and superior RT. Data were analyzed using a multivariate linear mixed model. MAIN OUTCOME MEASURES: The relationship between mTD asymmetry (hemifield, central, middle, and peripheral) and both RT asymmetry and other factors (intraocular pressure, axial length, corneal radius, age, gender, mean deviation, refraction, and visual acuity) was assessed. RESULTS: The inferior RT was significantly larger than the superior RT (P < 0.001). Hemifield mTD asymmetry was related to RT asymmetry (P = 0.017). These relationships were significant in the middle (P = 0.029) and peripheral areas (P = 0.023), but not in the central area (P = 0.40). Other factors were not related to mTD asymmetry. CONCLUSIONS: Vertical asymmetry of the posterior pole was related to the vertical asymmetry of glaucomatous VF damage.

Molecular targeting of HER2-overexpressing biliary tract cancer cells with trastuzumab emtansine, an antibody-cytotoxic drug conjugate.

PURPOSE: Trastuzumab emtansine (T-DM1) provides clinical benefit in breast cancers overexpressing human epidermal growth factor receptor 2 (HER2). However, its efficacy against biliary tract cancers (BTC) has not been evaluated. In this study, the effectiveness of T-DM1 in various BTC cell lines and xenograft models with different levels of HER2 expression was investigated. METHODS: HER2 expression status in xenografts and patient tissue microarrays was assessed by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH). Cell-surface HER2 expression levels and cell growth inhibition in response to T-DM1 were examined in 17 BTC cell lines. The antitumor activity of T-DM1 was evaluated in four xenograft mouse models with different levels of HER2 expression. The effects of T-DM1 on HER2 signaling, antibody-dependent cell-mediated cytotoxicity (ADCC), cell cycle, and apoptosis were assessed in vitro. RESULTS: Cell-surface expression of HER2 was observed in both gallbladder carcinoma and cholangiocarcinoma tissues. The anti-proliferative activity of T-DM1 was higher in BTC cell lines and breast cancer cell lines with higher levels of HER2 expression. The HER2 status (IHC score|HER2-to-CEP17 ratio by FISH testing) of each BTC xenograft was 3 +|8.3 for KMCH-1, 2 +|4.7 for Mz-ChA-1, 1 +/0|1.4 for OCUG-1, and 0|1.1 for KKU-100, and T-DM1 showed antitumor activity in proportion to the HER2 status. T-DM1 inhibited HER2 signaling and induced ADCC, mitotic arrest, and apoptosis in KMCH-1 cells. CONCLUSIONS: T-DM1 exhibited preclinical activity in HER2-overexpressing BTC. Further evaluation in clinical studies is warranted.

Scanning laser polarimetry with enhanced corneal compensation in patients with open-angle glaucoma.

AIMS: To compare the retinal nerve fiber layer thickness (RNFLT) parameters obtained with newly introduced GDx with enhanced corneal compensation (ECC) and those with GDx with variable corneal compensation (VCC) and to evaluate their reproducibility and the correspondence with visual field damage (VFD) in total or sectorized fields in association with refractive errors in open-angle glaucoma (OAG) patients. PATIENTS AND METHODS: Measurement reproducibility was assessed in 30 normal and 30 OAG eyes. Correlation between the RNFLT parameters and the corresponding VFD was evaluated in 58 OAG eyes. RESULTS: All parameters of both GDx VCC and ECC showed high intraclass correlation coefficients among the repeated measurements (0.89 to 0.99), suggesting good reproducibility. All RNFLT parameters were significantly correlated between VCC and ECC (intraclass correlation coefficient=0.58-0.92, P<0.001) though they were significantly different. In OAG eyes, correlation between temporal, superior, nasal, inferior, temporal average and mean deviation of VFD was similar in both algorithms (Rs=0.58 and 0.53, P<0.001). When the OAG eyes were subgrouped by refractive error at -5 D, the correlation was significant for both ECC and VCC in the lower myopic group (>-5 D) (Rs=0.71 and 0.74, P<0.0001) but was significant only for ECC in the higher myopic group (

Comparison of Esterman disability scores obtained using Goldmann perimetry and the Humphrey field analyzer in Japanese low-vision patients.

PURPOSE: To compare the Esterman Disability Score (EDS) obtained with Goldmann perimetry (GP) testing and the Humphrey field analyzer (HFA) in low vision Japanese subjects. Subjects were also divided into groups by diagnosis to examine how disease influences EDS measurements. METHODS: The EDS was obtained using GP (GP-EDS) and the built-in testing program of the HFA (HFA-EDS). Tests were performed within 3 months of each other. Regression analyses were used to examine the relationship between GP-EDS and HFA-EDS. RESULTS: A total of 128 visually impaired subjects were included in this study. Subjects had low vision because of glaucoma (57 subjects), age-related macular degeneration (AMD, 17 subjects), retinitis pigmentosa (RP, 17 subjects), and other causes (37 subjects). The GP-EDS obtained was well-correlated with HFA-EDS (r = 0.87, P < 0.001) and it was possible to estimate HFA-EDS from GP-EDS. The GP-EDS was significantly lower than the HFA-EDS in eyes with glaucoma and RP. There was no significant difference between EDS values in eyes with AMD or other disease. CONCLUSION: The GP-EDS correlated well with the HFA-EDS. However, the relationship between the EDS measured with the two different testing modalities varies by disease.

Evaluating the Usefulness of MP-3 Microperimetry in Glaucoma Patients.

PURPOSE: The purpose of the current study was to evaluate the test-retest reproducibility and structure-function relationship of the MP-3 microperimeter, compared against the Humphrey Field Analyzer (HFA). METHODS: Design: Reliability and validity study. SETTING: Institutional, or clinical practice. STUDY POPULATION: Thirty eyes of 30 primary open-angle glaucoma patients were enrolled. OBSERVATION PROCEDURES: Visual fields (VF) were measured twice with the MP-3 and HFA instruments, using the 10-2 test grid pattern in both perimeters. Ganglion cell complex (GCC) thickness was measured using optical coherence tomography (OCT). Test-retest reproducibility was assessed using the mean absolute deviation (MAD) measure at all 68 VF test points, and also the intraclass correlation coefficient (ICC) of the repeated VF sensitivities. The structure-function relationship between VF sensitivities (measured with MP-3 or HFA) and GCC thickness (adjusted for the retinal ganglion cell displacement) was analyzed using linear mixed modeling. MAIN OUTCOME MEASURE: Reproducibility and structure-function relationship. RESULTS: The average measurement duration with the HFA 10-2 was 7 minutes and 6 seconds (7m06s) ± 0m49s (mean ± standard deviation). A significantly (P < .001, paired Wilcoxon test) longer measurement duration was observed for the MP-3 test: 10m29s ± 2m55s. There were no significant differences in MAD and ICC values between HFA (MAD; 0.83 ± 0.69 dB and ICC: 0.89 ± 0.69, mean ± standard deviation) and MP-3 (MAD: 0.65 ± 0.67 dB and ICC: 0.89 ± 0.69). MP-3 VF sensitivities had a stronger structure-function relationship with GCC thickness compared to HFA. CONCLUSIONS: The MP-3 microperimeter has a similar test-retest reproducibility to the HFA but a better structure-function relationship.

Changes in Axial Length and Progression of Visual Field Damage in Glaucoma.

Purpose: To investigate the relationship between axial length (AL) elongation and progression of primary open-angle glaucoma (POAG). Methods: AL was measured twice over a 5.1 ± 0.76 (mean ± standard deviation: SD) year period in 125 eyes of 72 patients with POAG. The eyes were divided into not long (AL < 26 mm, 80 eyes) and long (>26 mm, 45 eyes) groups. During this period, patients' visual fields (VFs) were measured with the Humphrey Field Analyzer 12.4 ± 7.5 times and intraocular pressure (IOP) was measured with Goldmann applanation tonometry 27.0 ± 7.5 times. The relationship between the mean total deviation (mTD) progression rates in the whole field and superior and inferior hemifield, as well as in 10 VF sectors, and the variables of age, mean IOP, SD of IOP, AL, difference in AL (△AL), and mTD value at baseline was examined. Results: There was a significant difference between AL at baseline and AL at repeat measurement (P < 0.0001). △AL was 0.035 ± 0.10 mm. An increase in △AL was significantly related to AL at baseline (P = 0.027), but not to age, mean IOP, and SD of IOP. △AL was related to the progression of mTD in the inferior hemifield (slower mTD progression was associated with increased △AL), but not in the whole field or superior hemifield. Increased △AL was related to slower progression rates in 2 of 10 sectors, both in the inferior hemifield. Conclusions: The main finding was that an increase in AL was significantly related to slower VF progression in the inferior hemifield.

Mapping the Central 10° Visual Field to the Optic Nerve Head Using the Structure-Function Relationship.

Purpose: To investigate the structure-function mapping in the central 10° by relating Humphrey field analyzer (HFA) 10-2 visual field (VF) and circumpapillary retinal nerve fiber layer (cpRNFL) thickness from spectral-domain optical coherence tomography (SD-OCT). We also compared the obtained results with a previously reported mapping between 10-2 VF and the optic disc. Methods: In 151 eyes of 151 POAG patients and 35 eyes from 35 healthy participants, cpRNFL thickness measurements were obtained using SD-OCT and the 10-2 VF was measured with the HFA. The relationship between visual sensitivity and cpRNL thickness values in the temporal 180° was analyzed using least absolute shrinkage and selection operator (LASSO) regression. The optic disc angle corresponding to each VF test point was then derived using the coefficients from the optimal LASSO regression. Results: The structure-function map obtained was largely consistent with the mapping reported previously; superior central VF test points correspond to a more vulnerable area of the optic disc, more distant toward the inferior pole from the center of the temporal quadrant (9:00 o'clock for the right eye) while inferior VF test points correspond closer to the center of the temporal quadrant. The prediction error tended to be large in the 'more vulnerable area' in the map reported previously. Conclusions: The structure-function map obtained largely confirms the previously reported map; however, some important differences were observed.