A Path Analysis of Effects of Patients' Underlying Conditions, Treatment Satisfaction, and Adherence on Quality of Life Among Korea Glaucoma Patients.

PRéCIS:: This observed patient-specific features and treatment-driven conditions that were significantly associated with the impairment of health-related quality of life (HRQOL) among glaucoma patients. The results suggest that more systematic strategies should be implemented to improve an HRQOL. PURPOSE: To determine factors contributing to an HRQOL and assess total, direct and indirect, effects that may exist between the determinants using path analysis. MATERIALS AND METHODS: Data were derived from previous Korea glaucoma outcomes research. A total of 847 glaucoma outpatients with ≤2 years of eye-drop use were included in the present study. Including factors and their hypothetical pathways to an HRQOL were based on the literature review and consultation with specialists. Age, sex, comorbidities, and education levels were included as underlying conditions and treatment patterns were defined by the number of daily instillations of prescribed eye-drops. Treatment satisfaction and adherence were estimated using a Treatment Satisfaction Questionnaire for Medication, which assessed side-effects, effectiveness, convenience, global satisfaction, and pill count. An HRQOL was assessed by EQ-5D and EQ-visual analogue scale (EQ-VAS). RESULTS: In EQ-5D analysis, male individuals showed total effects (ß=0.102, P=0.0026), including both direct (ß=0.076, P=0.0095) and indirect effects (ß=0.0253, P=0.0020), which were mediated by treatment satisfaction in the side effects and global satisfaction categories. Higher education (ß=0.197, P=0.0020) and satisfaction in the side effect (ß=0.095, P=0.0076) and global satisfaction (ß=0.075, P=0.0414) categories were found to have direct effects on EQ-5D. For EQ-VAS, higher education levels had significant total effects (ß=0.153, P=0.0020) accounting for direct effects (ß=0.131, P=0.0030) and indirect effects (ß=0.0223, P=0.0531) through global satisfaction. In addition, male individuals had indirect effects (ß=0.274, P=0.0165), which was indirectly mediated by satisfaction in the global satisfaction category. Comorbidity (ß=-0.096, P=0.0090) and satisfaction in the effectiveness (ß=0.094, P=0.0302), convenience (ß=0.076, P=0.0390), and global satisfaction (ß =0.144, P=0.0020) categories showed indirect effect on EQ-VAS. CONCLUSION: Higher education and better treatment satisfaction had positive effects on HRQOL both in direct and indirect ways whereas comorbidities indirectly showed negative associations with HRQOL.

Treatment patterns and medication adherence of patients with glaucoma in South Korea.

BACKGROUND/AIMS: This study aimed to investigate treatment patterns and medication adherence of glaucoma. It also identified key factors associated with non-adherence. METHODS: It was a cross-sectional, observational study. Patients who use eye-drops for ≤2 years were recruited at 15 eye clinics from March to November 2013. Data were collected through self-administered questionnaires and medical chart review. Medication adherence was evaluated using patients' self-report on pill count and defined as patients' administering drug for ≥80% of prescribed days. Medication adherence rate was calculated by dividing actual number of administration from total prescribed number of administration for 7 days. Patients whose self-reported prescription was different from total daily doses of physicians' prescription were considered as non-adherent. RESULTS: A total of 1050 patients included, and medication adherence rate was evaluated in 1046 patients whose verification of adherence was available. Of the total, 27.4% were non-adherent, and the medication adherence rates of the total, the adherent, and the non-adherent were 90.6±17.8%, 96.8±5.5% and 56.6±24.7%, respectively. The most commonly used medication was prostaglandin (PGA) alone and the second was combination of two-class (ß-blocker and carbonic anhydrase inhibitor (CAI)) and three-class combination of PGA, ß-blocker and CAI followed. In multivariate analysis, the risk of non-adherence was 1.466 times greater in males than in females (95% CI 1.106 to 1.943) and 1.328-fold greater as the daily number of administration was increased (95% CI 1.186 to 1.487). CONCLUSION: Approximately, one-third of the patients were non-adherent, and males and increased daily number of administration were associated with non-adherence. It highlights that more systematic treatment strategies should be considered for better medication adherence, leading to effective glaucoma management.

Evaluation of Interocular Retinal Nerve Fiber Layer Thickness Symmetry as a Diagnostic Modality for Glaucoma.

PURPOSE OF THE STUDY: The purpose of study was to measure the diagnostic utility of interocular retinal nerve fiber layer (RNFL) symmetry and interocular RNFL thickness comparison. METHODS: Both eyes of 103 normal subjects and 106 glaucoma patients (31 patients with early glaucoma and 75 patients with moderate to severe glaucoma) received comprehensive ophthalmologic evaluation including visual field testing and optic disc scanning using optical coherence tomography. RNFL thickness values for 256 measurement points were rearranged according to a new reference line connecting the optic disc center and the foveola. The interocular RNFL thickness symmetry value and absolute and fractional interocular difference in RNFL thickness were calculated and compared between groups. Area under the receiver operating characteristic curves (AUROCs) were calculated and compared. RESULT: Among the parameters reflecting whole RNFL status, the corrected interocular RNFL thickness symmetry exhibited the largest AUROCs at all glaucoma stages. RNFL thickness and absolute and fractional interocular difference in RNFL thickness exhibited largest AUROC in the inferotemporal area, regardless of glaucoma stage. In the early glaucoma group, absolute and fractional interocular RNFL thickness differences in the temporal and superotemporal areas exhibited equal to or larger AUROCs than RNFL thickness. The AUROCs for RNFL thickness were greater than those for absolute and fractional interocular RNFL thickness differences in the moderate to severe glaucoma group except in the nasal and temporal area. CONCLUSIONS: The corrected interocular RNFL thickness symmetry value is an effective diagnostic tool for glaucoma. Interocular comparison of RNFL thickness has good diagnostic performance and gives information about the RNFL beyond just the RNFL thickness itself.

Interocular retinal nerve fiber layer thickness difference in normal adults.

PURPOSE: To determine the interocular retinal nerve fiber layer (RNFL) thickness difference of normal subjects. METHODS: Both eyes of 230 normal adults received peripapillary RNFL thickness measurements using OCT. The effect of ocular cyclotorsion on the RNFL thickness profile was mathematically corrected. The fractional and absolute interocular RNFL thickness differences at 256 points of peripapillary area were calculated. We divided the subjects into 3 groups according to the locations of superior and inferior peak thickness, respectively, and compared the interocular RNFL thickness differences between the subgroups. RESULTS: The fractional interocular RNFL thickness difference exhibited smaller regional variations than the absolute interocular difference. The means of fractional interocular differences were 0.100 ± 0.077 in the temporal half area and 0.146 ± 0.105 in the nasal half area, and the tolerance limits for the 95th and 99 th distributions were about 0.246 and 0.344 in the temporal half area and 0.293 and 0.408 in the nasal half area, respectively. The fractional interocular differences of subgroups classified by the locations of superior and inferior peak RNFL thickness showed difference at smaller areas than the absolute interocular differences (19 and 8 points versus 49 and 23 points, respectively). CONCLUSION: Glaucoma can be strongly suspected, if interocular fractional RNFL thickness difference is over 25% at 5 consecutive points or over 35% at 3 consecutive points in the temporal half area. The fractional interocular comparison is a better diagnostic approach because the fractional interocular RNFL thickness difference is less influenced by the locations of peak RNFL thickness.

Interocular retinal nerve fiber layer thickness symmetry value in normal young adults.

PURPOSE: The aim of this study was to determine the normal range of interocular peripapillary retinal nerve fiber layer (RNFL) thickness symmetry value in young adults. Factors affecting interocular RNFL thickness symmetry were also investigated. MATERIALS AND METHODS: Both eyes of 241 ophthalmologically and neurologically normal subjects were scanned using optical coherence tomography (200×200 optic disc cube protocol). The effect of ocular cyclotorsion on interocular RNFL thickness symmetry was determined and mathematically accounted for. Symmetry value between the right and left RNFL thickness values was calculated. Linear regression analyses were used to identify correlations between the corrected interocular symmetry value and interocular differences in refractive error, axial length, superior and inferior temporal retinal artery and vein location, and optical coherence tomography signal strength. RESULTS: The mean interocular RNFL thickness symmetry value before and after correction of ocular cyclotorsion was 0.8791±0.0665 and 0.9044±0.0571 (P<0.001), respectively. Interocular differences in axial length, inferior temporal retinal arcade location, and refractive error were weakly and negatively correlated with the ocular cyclotorsion-corrected symmetry value (P<0.05). Anatomic differences between the eyes in the location of the superior temporal retinal artery and vein were strongly correlated with the corrected symmetry value (P<0.01, R=0.208). CONCLUSIONS: On the basis of the data obtained here from normal individuals, a corrected symmetry value of <0.77 might indicate the presence of pathologic conditions affecting the RNFL. Interocular RNFL thickness symmetry was influenced more heavily by interocular superotemporal vessel location than by anisometropia.

Cases of pseudophakic pseudoexfoliation in glaucoma patients.

We present cases of primary open angle glaucoma patients without previous history of pseudoexfoliation who developed pseudoexfoliative materials on the anterior surface of the intraocular lens after cataract surgery. Among 5 unilateral pseudophakic pseudoexfoliation cases, 3 showed a more advanced state of glaucoma in the affected eye. The other 2 cases showed progression of glaucoma in the affected eye after the development of pseudophakic pseudoexfoliation, while the unaffected eyes remained stable. In the latter 2 cases, control of intraocular pressure was difficult, and more glaucoma medication was needed in the affected eye. Pseudophakic pseudoexfoliation in glaucoma patients with no history of pseudoexfoliation syndrome or pseudoexfoliative glaucoma has not been reported. In our cases, the eyes which developed pseudophakic pseudoexfoliation showed a more advanced state of glaucoma, more difficulty controlling intraocular pressure, and faster progression of glaucoma. More observation is needed, but we cautiously postulate that pseudophakic pseudoexfoliation may have a role as a clinical risk factor in the prediction of glaucoma progression.

Angle closure in the Namil study in central South Korea.

OBJECTIVE: To assess the prevalence and associated risk factors of angle closure in a defined population as part of the Namil Study. METHODS: In this cross-sectional epidemiologic study for residents aged 40 years or older in Namil-myon, a rural area in central South Korea, the examination included slitlamp biomicroscopy, applanation tonometry, gonioscopy, autorefraction, fundus photography, corneal thickness measurement, visual field test with frequency-doubling technology, and anterior chamber depth (ACD) and axial length (AL) measurements with partial coherence interferometry. Standard automated field test and optical coherence tomography or scanning laser polarimetry were performed to confirm the glaucomatous visual field/optic disc damage. Angle closure included primary angle-closure suspect (PACS), primary angle closure (PAC), and primary angle-closure glaucoma (PACG). Definitions of PACS, PAC, and PACG were based on the recommendations from the International Society for Geographical &Epidemiological Ophthalmology. RESULTS: Among the 1426 individuals enrolled for the assessment, with exclusion of cataract surgery, the prevalence rates of PACS, PAC, PACG, and overall angle closure in at least 1 eye were 2.0% (95% CI, 1.3%-2.8%), 0.5% (95% CI, 0.1%-0.9%), 0.7% (95% CI, 0.3%-1.1%), and 3.2% (95% CI, 2.3%-4.2%), respectively. Multivariate analysis found that older age (odds ratio [OR], 1.8797; 95% CI, 1.4624-2.4162), shallower ACD (OR, 0.9982; 95% CI, 0.9977-0.9987), and shorter AL (OR 0.9978; 95% CI, 0.9969-0.9988) (P < .001 for each) were significantly associated with angle closure. CONCLUSIONS: The overall prevalence of angle closure was 3.2% in the present study. On the basis of these findings, increasing age, shallower ACD, and shorter AL appear to be associated with angle closure. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00727168.

Analysis of systemic endothelin-1, matrix metalloproteinase-9, macrophage chemoattractant protein-1, and high-sensitivity C-reactive protein in normal-tension glaucoma.

PURPOSE: To investigate the roles of vascular dysregulation and inflammation in normal-tension glaucoma (NTG), we determined the plasma levels of endothelin-1 (ET-1), matrix metalloproteinase-9 (MMP-9), macrophage chemoattractant protein-1 (MCP-1), and high-sensitivity C-reactive protein (hs-CRP). MATERIALS AND METHODS: Forty-five patients with NTG and age-matched 35 healthy controls were enrolled in this study. Blood samples from all subjects were assayed for ET-1, MMP-9, MCP-1, and hs-CRP concentrations and other systemic factors. RESULTS: There were no significant differences in hemoglobin, hematocrit, RBC count, WBC count, platelet count, fasting glucose, HbA1c, total cholesterol, triglyceride, LDL, and HDL between the NTG and control groups. The systemic levels of ET-1 and MCP-1 were significantly higher in the NTG group than in the control group (p = 0.05 and 0.02, respectively). The MMP-9 and hs-CRP levels were not significantly different between the NTG and control groups. CONCLUSIONS: After excluding patients with cardiovascular and other systemic diseases, plasma ET-1 and MCP-1 levels were elevated in patients with NTG. The MMP-9 and hs-CRP levels were not significantly different in NTG. Increased ET-1 and MCP-1 levels suggest that ischemia/inflammation may play a role in the pathogenesis of NTG.

Expression of the Na+-K+-2Cl(-)-cotransporter 2 in the normal and pressure-induced ischemic rat retina.

PURPOSE: To evaluate the expression of the Na(+)-K(+)-2Cl(-)-cotransporter 2 (NKCC2) in the ischemic rat retina. METHODS: Retinal ischemia was induced by pressures 90 to 120 mmHg, above systemic systolic pressure. Immunohistochemistry and western blot analysis were performed. RESULTS: NKCC2 is expressed in the normal retina and its expression is increased by ischemia caused by intraocular pressure elevation. NKCC2 immunoreactivity was observed mainly in axon bundles of ganglion cells and horizontal cell processes in the retina. NKCC2 expression continuously increased with a peak value 3 days (to 415% of normal levels) after ischemic injury, and then gradually decreased to 314% of controls until 2 weeks post injury. The mean density of NKCC2-labeled ganglion cells per mm(2) changed from 1,255 ± 109 in normal retinas to 391 ± 49 and 185 ± 37 at 3 days and 2 weeks after ischemia, respectively (p < 0.05), implying cell death of ganglion cells labeled with NKCC2. CONCLUSIONS: Taken together, these results suggest that NKCC2, which is expressed in retinal ganglion and horizontal cells, may contribute to cell death by ischemic injury in the retina, although the molecular mechanisms involved remain to be clarified.

Level of vascular endothelial growth factor in tenon tissue and results of glaucoma surgery.

OBJECTIVE: To determine the levels of vascular endothelial growth factor (VEGF) in both the aqueous humor and Tenon tissue in patients with primary open angle glaucoma (POAG) and the associations between the VEGF and outcomes of glaucoma surgery. METHODS: The study involved 19 patients with POAG who were scheduled to undergo glaucoma surgery owing to uncontrolled intraocular pressure (IOP) and 17 control subjects who were scheduled to undergo cataract surgery. At the time of surgery, about 0.1 mL of aqueous humor was collected through an anterior chamber paracentesis and a 44-mm Tenon tissue sample was cut from the eye. Concentrations of VEGF were analyzed by enzyme-linked immunosorbent assay. Spearman correlation and regression analysis were used to assess the relationship with VEGF level to the clinical characteristics and postoperative IOP. RESULTS: The VEGF in Tenon tissue was significantly elevated in patients with POAG compared with control subjects(P=.001). When patients with POAG were divided into success or failure groups 1 year following surgery, the VEGF levels were significantly higher in the Tenon tissue of the failure group compared with the success group(P=.014). The preoperative IOP was significantly related to the VEGF level in Tenon tissue in both the univariate(P=.001) and multivariate (P=.012) regressions. CONCLUSIONS: The VEGF level in Tenon tissue at the time of surgery was significantly related to 1-year surgical outcomes of glaucoma surgery, and it was significantly associated with the final IOP in patients with POAG.

Imaging of trabeculectomy blebs with Visante anterior segment optical coherence tomography after digital ocular compression.

PURPOSE: We investigated changes in intrableb morphology of functioning trabeculectomy blebs with anterior segment optical coherence tomography (AS-OCT) after digital ocular compression. METHODS: Sixty-eight patients who underwent fornix-based trabeculectomy were recruited from Seoul St. Mary's Hospital. Intraocular pressure (IOP) and AS-OCT images were taken before and after ocular compression. Bleb height and wall thickness and height and length of the internal cavity were measured by AS-OCT. The hyporeflective areas and number of microcysts were checked on both vertical and horizontal images. AS-OCT parameters for IOP change, bleb morphology, and interval between surgery and examination were compared. RESULTS: Ocular compression yielded significant changes for all AS-OCT parameters other than maximum bleb wall thickness in the 6- to 12-month period after surgery. Correlation between IOP change and AS-OCT parameters was greatest for the horizontal and vertical length of the internal cavity (Spearman rank correlation coefficient ρ = 0.717, P < 0.0001, and ρ = 0.866, P < 0.0001, respectively). Response to ocular compression in cystic blebs was mainly enlargement of the internal cavity and increase in bleb height. However, in diffuse filtering blebs, increases in the size of the hyporeflective areas and the number of microcysts were the main findings. From 12 months postoperatively, changes in AS-OCT intrableb parameters were significantly reduced, showing no difference after ocular compression. CONCLUSION: Digital ocular compression may be useful in maintaining bleb morphology when it is used for 6 months postoperatively. Response to ocular compression as assessed by bleb morphology was different.

Effect of myopia on the thickness of the retinal nerve fiber layer measured by Cirrus HD optical coherence tomography.

PURPOSE: To evaluate the effect of myopia on the peripapillary retinal nerve fiber layer (RNFL) thickness measured by Cirrus HD optical coherence tomography (OCT). METHODS: Comprehensive ophthalmic examinations were performed, including measurement of visual acuity, refraction, and axial length on 269 subjects (age, 19-26 years) with no ophthalmic abnormality. Further, 200 x 200-cube optic disc scans of the subjects' eyes were obtained with Cirrus HD OCT. The RNFL thickness at 256 points of the RNFL thickness profile and the average RNFL thickness were recorded. The correlations between these values and the axial length and spherical equivalent (SE) of refractive errors were then analyzed by simple linear regression, before and after adjustment of the ocular magnification. RESULTS: Before ocular magnification adjustment, the uncorrected average RNFL thickness decreased as the axial length increased and as the SE decreased. However, after the adjustment, the corrected average RNFL thickness exhibited no correlation with the spherical equivalent and a weak positive correlation with the axial length. Myopia also affected the RNFL thickness distribution. As the axial length increased and the spherical equivalent decreased, the thickness of the temporal peripapillary RNFL increased and that of the superior, superior nasal, inferior, and inferior nasal peripapillary RNFL decreased. CONCLUSIONS: The axial length affected the average RNFL thickness, and myopia affected the RNFL thickness distribution. High myopes are likely to exhibit different RNFL distribution patterns. Since ocular magnification significantly affects the RNFL measurement in such patients, it should be considered in diagnosing glaucoma.

Analysis of peripapillary retinal nerve fiber distribution in normal young adults.

PURPOSE. To determine the anatomic variations in the peripapillary retinal nerve fiber layer (RNFL) thickness distribution and the relationship between these anatomic variations and other ocular variables. METHODS. A complete ophthalmic examination, including measurement of visual acuity, refraction, and axial length, was performed on 269 subjects with no ophthalmic abnormalities. Further, fundus photographs and optic disc cube scans of the subjects' eyes were obtained with a fundus camera and spectral domain OCT (Cirrus HD-OCT; Carl Zeiss Meditec, Inc., Dubin, CA), respectively. The distance between the foveola and the center of the optic nerve head was measured. The correlations of the angles of the peaks in the RNFL thickness profile with the axial length, spherical equivalent of refractive error (SE), and distance between the foveola and optic disc center were analyzed by simple linear regression. RESULTS. Considerable interindividual variations were found in the angles of the peaks in the RNFL thickness profile. Further, the angles in the eyes in each individual showed significant differences. The angles of the superior and inferior first peak correlated significantly with the SE, axial length, and distance between the foveola and optic disc center. CONCLUSIONS. Subjects with increased distance between the foveola and optic disc center are likely to have a temporal shift in peak RNFL thickness. RNFL profiles with horizontally deviated peak RNFL thickness differ considerably from the normative data provided with the HD-OCT system. The variations in RNFL thickness profiles should be taken into account.

Synaptic connections of cone bipolar cells that express the neurokinin 1 receptor in the rabbit retina.

We have investigated and further characterized, in the rabbit retina, the synaptic connectivity of the ON-type cone bipolar cells that are immunoreactive for an antibody against the neurokinin-1 receptor (NK1R). NK1R-immunoreactive bipolar cell axons terminate in stratum 4 of the inner plexiform layer. The axons of NK1R-positive bipolar cells receive synaptic inputs from amacrine cells through conventional synapses and from putative AII amacrine cells via gap junctions. The major outputs from NK1R-positive bipolar cells make contacts with amacrine cell processes. The most frequent postsynaptic dyads comprise two amacrine cell processes. Double-labeling experiments with antibodies against NK1R and either calretinin or glycine have demonstrated that NK1R-immunoreactive bipolar cells form gap junctions with AII amacrine cells. Thus, NK1R-positive cone bipolar cells, together with calbindin-positive cone bipolar cells, may play an important role in transferring rod signals to the ON-type ganglion cells of the cone pathway in the rabbit retina.

Ganglion cell death in rat retina by persistent intraocular pressure elevation.

Glaucoma is characterized by loss of retinal ganglion cells (RGCs) and their axons. Retrograde axoplasmic transport blockade and excitotoxicity were proposed to be a major cause of RGC apoptosis. We conducted this study to characterize the episcleral vessel cauterization glaucoma model in the rat with respect to decreased retrograde axoplasmic flow and subsequent apoptotic RGC death. After episcleral vessels were cauterized in Sprague-Dawley rats, Fluorogold was injected into their superior colliculi by stereotactic method. Retrograde axoplasmic flow and TUNEL-stained apoptotic dead cells were observed microscopically. Elevated intraocular pressure was maintained for up to 6 weeks during follow-up. Retrograde axoplasmic flow to the rat retina was significantly decreased. Apoptotic RGC was selectively TUNEL-stained in the retina, especially at the ganglion cell layers. We concluded that elevated intraocular pressure caused apoptotic RGC death through retrograde axoplasmic flow blockage. Further studies will elucidate the neuroprotection strategies in glaucoma patients.