Effects of Glaucoma Medication on Dry Eye Syndrome and Quality of Life in Patients with Glaucoma.

PURPOSE: To investigate ocular surface diseases and changes in the quality of life of patients using glaucoma medications. METHODS: Participants were divided into the normal (31 individuals, 62 eyes) and glaucoma medication (30 patients, 60 eyes) groups. Changes in tear break-up time, lipid layer thickness (LLT), corneal and conjunctival staining scores, ocular surface disease index (OSDI), and Visual Function Questionnaire 25 (VFQ-25) score were assessed for 1 year. RESULTS: The change in mean LLT was lower in glaucomatous eyes than in control eyes (p = 0.019) after 1 year. The results of OSDI deteriorated (p' = 0.008), but conjunctival staining and Schirmer test results showed improvement in glaucomatous eyes compared to those in control eyes (p' =0.035 and 0.009, respectively). The average LLT decreased at 6 and 12 months, but there was no change at 24 months. In pairwise analysis, the decrease in LLT over the first 6 months was statistically significant (p < 0.001) and remained unchanged until 24 months. Among the VFQ items, scores for near activity and social function deteriorated over 1 year in the medication group (p' = 0.033 and 0.015, respectively). However, there was no difference in the total VFQ score. CONCLUSIONS: Significant reduction in LLT and deterioration of OSDI were observed in the medication group compared to the control group. However, this deterioration was observed only in the first 6 months. There was no significant difference in the VFQ total score. Nonetheless, there were significant differences in near activity and social function between the control and medication groups. Therefore, the results of this study showed that although glaucoma medication worsened eye dryness, the change was limited and did not worsen the quality of life. Glaucoma medication should be used with the consideration that they can limit near activity and social functioning.

Effect of systemic blood pressure on optical coherence tomography angiography in glaucoma patients.

BACKGROUND: The association between retinal microvascular structure and glaucoma has been revealed in multiple studies using optical tomography angiography (OCTA), but limited information on the macular vessel density (mVD) in patients with glaucoma is available. In this study, we tried to identity the factors that affected macular VD (mVD) in glaucomatous eyes. METHODS: This retrospective cross-sectional study evaluated OCT and OCTA images from 92 eyes from 58 healthy subjects and 179 eyes from 103 glaucoma patients using the SD-OCT database from July 2017 to July 2018. Glaucomatous eyes were further divided into two groups according to history of disc haemorrhage (DH). Association between mVD and demographic characteristics, ganglion cell-inner plexiform layer (GCIPL) thickness, visual field mean deviation (MD) and systemic blood pressure was analysed in each group. RESULTS: In both healthy and glaucomatous eyes, mVD was inversely associated with age (ß = -0.035, P = 0.025; ß = -0.039, P = 0.018). In the glaucomatous eyes, mVD was significantly decreased, as the MD value was worse (ß = 0.109, P = 0.002). In glaucomatous eyes with DH, mVD decreased as blood pressure increased (ß = -0.111, P = 0.003) CONCLUSIONS: Reduced mVD is more common in older individuals in both healthy and glaucomatous eyes, and correlates with functional deterioration than structural damage in glaucomatous eyes. In glaucomatous eyes with DH, high systemic BP is associated with a reduction in mVD. This may indicate that glaucoma patients with DH are more susceptible to vascular damage secondary to hypertension.

Development of a nomogram using fundus photography to predict glaucoma progression in patients showing disc hemorrhage.

To develop a nomogram to predict the progression of glaucoma by fundus photography in patients with disc hemorrhage. Retrospective review of the medical records of patients with disc hemorrhage, which was detected during follow up with open angle glaucoma, from January 2010 to March 2018. Patients were divided into glaucoma progression (n = 52) or non-progression (n = 38) groups. We assessed proximal location and morphology of disc hemorrhage; relationship to retinal nerve fiber layer defects with disc hemorrhage; and angular extent of disc hemorrhage, between groups using fundus photography. Multiple logistic regression analysis was performed to select prognostic factors, and we constructed a nomogram to predict glaucoma progression. The number of disc hemorrhage at the border of retinal nerve fiber layer defects (P = 0.001) and peripapillary disc hemorrhage (P = 0.008) were significantly higher in the progression group. We used angular extent; location of disc hemorrhage with retinal nerve fiber layer defects; and proximal location of disc hemorrhage to construct the nomogram. The area under the receiver operating characteristic curve of the nomogram was 0.847. We created the nomogram using fundus photography in patients showing disc hemorrhage as a novel and accurate screening method to predict glaucoma progression and aid clinicians to decide on the best treatment plan.

Factors associated with macular vessel density measured by optical coherence tomography angiography in healthy and glaucomatous eyes.

PURPOSE: To investigate factors associated with macular vessel density and to analyze their effects according to glaucoma stage. STUDY DESIGN: Retrospective cross-sectional study. METHODS: A total of 72 healthy eyes and 147 open-angle glaucomatous eyes were studied. All eyes underwent optical coherence tomography and visual field examinations. Clinical variables were compared according to the glaucoma stage. Relationships between macular vessel density (mVD) and other variables were analyzed using linear regression and segmented analyses. RESULTS: Age (P = 0.010) and signal strength (P < 0.001) were associated with macular vessel density in healthy eyes. In glaucomatous eyes, age, signal strength, ganglion cell-inner plexiform layer (GCIPL) thickness, and mean deviation (MD) correlated with macular vessel density (all P ≤ 0.005). When analyzed by glaucoma stage, age correlated with macular vessel density in early (P = 0.017 and all P ≤ 0.012, respectively) and moderate (P = 0.002 and all P ≤ 0.001, respectively) glaucoma. Conversely, GCIPL thickness was associated with macular vessel density (P = 0.004). According to segmented analysis between MD and mVD, the MD value at the change point for mVD was -17.92 dB, which was much lower than that for GCIPL thickness (-5.83 dB). CONCLUSION: Signal strength was the most significant factor associated with macular vessel density in healthy and glaucomatous eyes. Other than signal strength, factors associated with macular vessel density of glaucomatous eyes vary according to the glaucoma stage. The segmented analysis suggests that mVD could be better than GCIPL thickness in predicting MD changes in moderate-to-advanced glaucoma.

Significance of dynamic contour tonometry in evaluation of progression of glaucoma in patients with a history of laser refractive surgery.

AIMS: In this study, we tested the hypothesis that intraocular pressure (IOP) parameters measured by dynamic contour tonometry (DCT) would be more relevant in progression of glaucoma when there is a history of laser refractive surgery (LRS) than the IOP parameters measured by Goldmann applanation tonometry (GAT) or calculated by correction formulae. METHODS: Ninety-eight eyes in 54 patients with open-angle glaucoma and a history of LRS were included in this retrospective study. IOP was measured by both GAT and DCT during follow-up. Baseline, mean, and peak IOP, IOP fluctuation, and IOP reduction were measured by each tonometry method. Corrected IOP parameters using central corneal thickness and mean keratometry values were also analysed. Clustered logistic regression was used to identify variables correlated with progression of glaucoma. Areas under the curve (AUCs) for correlated variables were also compared. RESULTS: The mean DCT value (OR 1.36, p=0.024), peak DCT value (OR 1.19, p=0.02) and pattern SD (OR 1.10, p=0.016) were significant risk factors for progression. There was a significant difference in the predictive ability of the mean DCT and GAT values (AUC 0.63 and 0.514, respectively; p=0.01) and of the peak DCT and GAT values (0.646 and 0.503, respectively, p=0.009). The AUCs for corrected IOP did not exceed those of DCT. CONCLUSIONS: IOP measurements were more associated with progression of glaucoma when measurements were obtained by DCT than by GAT or correction formulae in eyes with a history of LRS.

Meibomian gland dropout rate as a method to assess meibomian gland morphologic changes during use of preservative-containing or preservative-free topical prostaglandin analogues.

PURPOSE: To investigate the usefulness of meibomian gland (MG) dropout rate in the evaluation of MG morphological change associated with the use of prostaglandin for glaucoma treatment through the association between MG and the ocular surface parameters and medication duration and presence of preservative. METHODS: This cross-sectional study was conducted on 88 eyes of 88 patients who were diagnosed with glaucoma and used only Tafluprost as treatment. The patients were divided into four "user" groups: 1) 23 patients used preservative-free (PF) Tafluprost for 6 months; 2) 21 patients used preservative-containing (PC) Tafluprost for 6 months; 3) 23 patients used PF-Tafluprost for 24 months; 4) 21 patients used PC-Tafluprost for 24 months. Ocular surface parameters and the MG condition, including MG dropout rate and meiboscale, were evaluated. Multiple regression was used to identify associations. RESULTS: There were significant differences in age (p = 0.003), tear breakup time (p = 0.016), lid margin abnormality (p = 0.016), expressibility (p = 0.039), meiboscale (p<0.001), and MG dropout rate (p<0.001) among the 4 groups. MG dropout rate and meiboscale showed significant differences in all post hoc analyses, except for the comparison between the PF-Tafluprost and PC-Tafluprost 6-month user groups. Medication duration, preservative status, and meiboscale were significantly correlated with MG dropout rate (p<0.001, p = 0.024, p<0.001, respectively). In the 6-month user group, preservative status significantly correlated with MG dropout rate (p = 0.015). However, in the 24-month user group, meiboscale was the only parameter significantly associated with MG dropout rate (p<0.001). CONCLUSION: MG dropout rate in patients using Tafluprost showed a significant correlation with medication duration and preservative status. This result indicates MG dropout rate reflects MG morphologic change associated with prostaglandin.

Nomogram Using Optical Coherence Tomography and Visual Field Parameters to Predict Brain Lesions in Patients with Bitemporal Hemianopia.

PURPOSE: This study aims to develop a nomogram to predict brain lesions in patients with complete or incomplete bitemporal hemianopia by combining results from optical coherence tomography (OCT) and visual field (VF) testing. MATERIAL AND METHODS: We reviewed the medical records of patients who underwent magnetic resonance imaging (MRI) to identify brain lesions due to bitemporal hemianopia between January 2010 and March 2017, retrospectively. The patients were divided into two groups based on MRI findings: brain-lesion (+) group that had brain lesions on MRI (n = 63), and brain-lesion (-) group without brain lesions on MRI (n = 16). We compared OCT and VF findings between the two groups to find factors that could predict a brain lesion. Multiple logistic regression analysis was performed to select prognostic factors, and we constructed a nomogram to predict brain lesions on MRI. RESULT: The VF mean deviation was lower (p = 0.011) and all sectors of peripapillary retinal nerve fiber layer thickness except the temporal region were thicker in the brain-lesion (+) group. However, there was no statistically significant difference in macular ganglion cell-inner plexiform layer between the two groups. The area under the receiver operating characteristic curve of the nomogram for predicting brain lesions on MRI was 0.916. CONCLUSION: We developed a nomogram using VF and OCT examinations as a novel and accurate screening method to predict brain lesions in patients with bitemporal hemianopia and aid ophthalmologists and other clinicians in deciding whether to further evaluate a patient by MRI.

Near and Distance Stereoacuity in Patients With Primary Open-angle Glaucoma.

PURPOSE: To compare near and distance stereoacuity between patients with primary open-angle glaucoma (POAG) and a control group, and to analyze the associations between stereoacuity and POAG severity. METHODS: This cross-sectional study compared near and distance stereoacuity between the POAG and control groups. The data from the POAG group were used to assess the associations between stereoacuity (both near and distance) and the severity of visual field (VF) defects (based on Hodapp-Anderson-Parrish classification and the VF index). RESULTS: The study included 94 eyes of 47 patients with POAG and 80 eyes of 40 control subjects. Near and distance stereoacuity were significantly lower in the POAG group than in the control group (both P<0.001). Near stereoacuity worsened with POAG severity in terms of both the Hodapp-Anderson-Parrish classification and VF index (P=0.007 and P=0.049, respectively). However, distance stereoacuity was not associated with POAG severity for either categorization (P=0.12 and P=0.57, respectively). The proportions of patients with reduced near stereoacuity and those with a lack of distance stereoacuity were higher in the POAG group than in the control group. CONCLUSIONS: Near and distance stereoacuity were significantly lower among patients with POAG than among control subjects. Near stereoacuity worsened with increasing POAG severity but distance stereoacuity did not. However, the proportion of patients with a lack of distance stereoacuity was higher in the POAG group than in the control group.

Asymmetry of Peak Thicknesses between the Superior and Inferior Retinal Nerve Fiber Layers for Early Glaucoma Detection: A Simple Screening Method.

PURPOSE: To assess whether the asymmetry in the peripapillary retinal nerve fiber layer (pRNFL) thickness between superior and inferior hemispheres on optical coherence tomography (OCT) is useful for early detection of glaucoma. MATERIALS AND METHODS: The patient population consisted of Training set (a total of 60 subjects with early glaucoma and 59 normal subjects) and Validation set (30 subjects with early glaucoma and 30 normal subjects). Two kinds of ratios were employed to measure the asymmetry between the superior and inferior pRNFL thickness using OCT. One was the ratio of the superior to inferior peak thicknesses (peak pRNFL thickness ratio; PTR), and the other was the ratio of the superior to inferior average thickness (average pRNFL thickness ratio; ATR). The diagnostic abilities of the PTR and ATR were compared to the color code classification in OCT. Using the optimal cut-off values of the PTR and ATR obtained from the Training set, the two ratios were independently validated for diagnostic capability. RESULTS: For the Training set, the sensitivities/specificities of the PTR, ATR, quadrants color code classification, and clock-hour color code classification were 81.7%/93.2%, 71.7%/74.6%, 75.0%/93.2%, and 75.0%/79.7%, respectively. The PTR showed a better diagnostic performance for early glaucoma detection than the ATR and the clock-hour color code classification in terms of areas under the receiver operating characteristic curves (AUCs) (0.898, 0.765, and 0.773, respectively). For the Validation set, the PTR also showed the best sensitivity and AUC. CONCLUSION: The PTR is a simple method with considerable diagnostic ability for early glaucoma detection. It can, therefore, be widely used as a new screening method for early glaucoma.

A case of atypical fibroxanthoma of subungual type: ultrasound and magnetic resonance imaging findings.

Subungual atypical fibroxanthoma is a rare mesenchymal skin tumor of intermediate malignancy. It classically presents as a relatively nondescript, erythematous nodule; it may ulcerate and bleed, but pain and pruritus are uncommon. In the differential diagnoses of subungual tumors, glomus tumor, soft tissue chondroma, keratoacanthoma, hemangioma, lobular capillary hemangioma, epidermal and mucoid cysts, squamous cell carcinoma, and malignant melanoma have been suggested. But atypical fibroxanthoma has not been included in the differential diagnoses. We report a case that occurred in a 56-year-old man with subungual atypical fibroxanthoma mimicking malignant soft tissue tumor in the right fifth toe.

Clinicopathological implications of EpCAM expression in adenocarcinoma of the lung.

BACKGROUND: The frequency of epithelial cell adhesion molecule (EpCAM) expression was investigated in non-small cell lung cancer (NSCLC) cells and human tissues, and its clinicopathological significance in adenocarcinoma of the lung was evaluated. MATERIALS AND METHODS: EpCAM expression was analysed by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry in human NSCLC cells. EpCAM protein expression was evaluated in 234 adenocarcinoma tissues using immunohistochemistry. RESULTS: A high expression level of EpCAM was observed in human NSCLC cells by flow cytometry and RT-PCR. EpCAM overexpression was detected in 120/234 (51.3%) surgically resected adenocarcinoma tissues. EpCAM overexpression occurred significantly more frequently in adenocarcinoma than in bronchioloalveolar carcinoma (p=0.02). The overall survival did not differ significantly between EpCAM-overexpressing and EpCAM-negative patients (p=0.40). CONCLUSION: These findings suggest EpCAM plays a role in the carcinogenesis of adenocarcinoma of the lung and might provide a promising molecule for targeted therapy in NSCLC.

Are there any ethnic differences in molecular predictors of erlotinib efficacy in advanced non-small cell lung cancer?

PURPOSE: This study investigated possible molecular predictors of outcome in Korean patients with advanced non-small cell lung cancer treated with erlotinib. EXPERIMENTAL DESIGN: One hundred and twenty patients received erlotinib and were followed prospectively. Ninety-two tissue samples were analyzed for epidermal growth factor receptor (EGFR) gene mutations (exons 18, 19, and 21), 88 for EGFR gene amplification by real-time PCR, and 75 for EGFR protein expression by immunohistochemistry. RESULTS: The overall tumor response rate was 24.2% (complete response, 4; partial response, 25) with 56.7% of disease control rate. With a median follow-up of 23.6 months, the median time to progression (TTP) was 2.7 months and the median overall survival was 12.9 months. EGFR gene mutations were found in 26.1% (24 of 92), EGFR gene amplification in 40.9% (36 of 88), and EGFR protein expression in 72% (54 of 75). There was a strong association between EGFR gene mutations and gene amplification (gamma = 0.241). Patients with EGFR gene mutations or gene amplification showed both better response rate (58.3% versus 16.2%, P < 0.001; 41.7% versus 17.3%, P = 0.012) and TTP (8.6 versus 2.5 months, P = 0.003; 5.8 versus 1.8 months, P < 0.001) and overall survival (not reached versus 10.8 months, P = 0.023; not reached versus 10.1 months, P = 0.033). By multivariate analysis, EGFR gene mutation was the only significant molecular predictor for TTP (hazard ratio, 0.47; 95% confidence interval, 0.25-0.89). CONCLUSIONS: Our findings indicate that EGFR gene mutation is a more predictive marker for improved TTP than EGFR gene amplification in erlotinib-treated Korean non-small cell lung cancer patients. Prospective studies from diverse ethnic backgrounds are required to determine the exact role of these molecular markers.

Comparison of microvessel density before and after peripheral blood stem cell transplantation in multiple myeloma patients and its clinical implications: multicenter trial.

Bone marrow angiogenesis has been reported to increase in several hematologic malignant diseases, including multiple myeloma. Because high-dose chemotherapy combined with autologous stem cell transplantation (SCT) improves the response rate, event-free survival, and overall survival in patients with multiple myeloma (MM), we studied the changes in bone marrow microvessel density (MVD) in 21 patients who underwent high-dose chemotherapy combined with autologous SCT to determine whether there was persistently increased angiogenesis at the time of response. Bone marrow biopsy specimens were obtained before and after SCT for each patient and immunostained with anti-CD34 antibodies for the identification of microvascular endothelial cells. The mean value of MVD in 21 MM patients at initial diagnosis was 46.0 +/- 24.0 and in healthy controls was 26.8 +/- 8.54 (P = .046). The mean MVD at initial diagnosis was 46.0 +/- 24.0 compared with 29.0 +/- 12.5 after achievement of response with SCT, and there was a statistically significant difference (P = .004). Sixteen of 21 patients (76.2%) had decreased MVD after SCT, and 5 patients were found to have a greater than 50% decrease in MVD after SCT. However, there was no difference in overall survival between the patient group with decreased MVD after SCT and that without decreased MVD (P = .9370). These results suggest that angiogenesis plays an important role in MM. In addition, the persistence of MVD at the time of response indicates continuous stimulus of microvessels by minimal residual disease even after SCT.