Rate of central corneal thickness changes in primary angle closure eyes: long-term follow-up results.

BACKGROUND: Central corneal thickness (CCT) and its association with intraocular pressure, which is a pivotal parameter in glaucoma management, has previously been reported. In this study, we intended to investigate the long-term change of CCT in terms of rate in eyes with primary angle-closure (PAC). Additionally, we aimed to analyze events that could affect CCT. METHODS: In this retrospective study, 26 patients with PAC who had a follow-up period of more than 5 years were analyzed. The rate of CCT changes from baseline was evaluated from the serial CCT measurements over the average follow-up period. The pattern of CCT change rate according to modes of treatment and history of angle-closure attack was analyzed using the repeated linear mixed model analysis. RESULTS: A total of 52 eyes were enrolled. The CCT reduction rate of the entire study population was - 0.72 ± 0.22 µm/yr (P = 0.001) with statistical significance. The CCT thinning rate of the laser peripheral iridotomy (PI) group was - 0.53 ± 0.25 µm/yr (P = 0.034) and that of the surgical trabeculectomy group was - 1.32 ± 0.43 µm/yr (P = 0.002), and it was not statistically significant (P = 0.112). The rate of CCT thinning in patients with a history of acute angle-closure attack was - 0.81 ± 0.31 µm/yr (P = 0.009) and that in patients without an attack was - 0.63 ± 0.30 µm/yr (P = 0.001), and it was not statistically significant (P = 0.680). Baseline CCT appeared to be the only significant factor affecting the rate of CCT changes (P < 0.001). CONCLUSIONS: We found a significant reduction in CCT over a long observation period in PAC eyes. We also found that the rates of CCT reduction were not affected by different treatment modalities or acute angle-closure attacks. The analysis of long-term CCT changes in conjunction with baseline CCT would also be helpful in the clinical evaluation of the PAC patients.

Peripapillary Microvascular Improvement and Lamina Cribrosa Depth Reduction After Trabeculectomy in Primary Open-Angle Glaucoma.

Purpose: To evaluate peripapillary microvascular changes in patients with primary open-angle glaucoma (POAG) after trabeculectomy using optical coherence tomography (OCT) angiography, and to determine the influence of lamina cribrosa (LC) displacement on changes in peripapillary microvasculature. Methods: The peripapillary retinal microvasculature and LC were imaged using OCT angiography and OCT-enhanced depth imaging, respectively. The microvasculature and LC depth (LCD) were measured before, and 1 week, 1 month, and 3 months after trabeculectomy. The microvascular improvement was arbitrarily defined as a reduction >30% of the area of vascular dropout (blue/black areas with <20% vessel density on the color-coded vessel density map). LCD was determined as the mean of vertical distance between the anterior LC surface and a reference plane of Bruch's membrane. Results: Thirty-one eyes of 31 POAG patients were included. At 3 months postoperatively, intraocular pressure (IOP) and LCD were significantly decreased from 26.3 ± 11.8 mm Hg to 12.5 ± 3.6 mm Hg, and 501.1 ± 130.2 µm to 455.8 ± 112.7 µm, respectively (all P < 0.001), compared with baseline. The microvascular improvement was observed in 19 eyes (61.3%) at 3 months after trabeculectomy. The maximal reductions in IOP and LCD were significantly greater in eyes with improved microvasculature compared to eyes without improvement (P = 0.020 and P = 0.005). The microvascular improvement was significantly associated with maximal reduction in LCD (odds ratio, 1.062; P = 0.026). Conclusions: Trabeculectomy can improve peripapillary retinal microcirculation in patients with POAG. This finding suggests that the reduction of LCD induced by lowering IOP may affect peripapillary microvascular improvement in eyes with POAG.

Diagnostic Ability of Retinal Nerve Fiber Layer Thickness Deviation Map for Localized and Diffuse Retinal Nerve Fiber Layer Defects.

Purpose. To evaluate the diagnostic ability of the retinal nerve fiber layer (RNFL) deviation map for glaucoma with localized or diffuse RNFL defects. Methods. Eyes of 139 glaucoma patients and 165 healthy subjects were enrolled. All participants were imaged with Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA, USA). A RNFL defect was defined as at least 10 contiguous red (<1% level) superpixels in RNFL deviation map. The area, location, and angular width of RNFL defects were automatically measured. We compared sensitivities, specificities, and area under the receiver operating characteristic curves (AUCs) of RNFL deviation map and circumpapillary RNFL thickness for localized and diffuse RNFL defects. Subgroup analysis was performed according to the severity of glaucoma. Results. For localized defects, the area of RNFL defects (AUC, 0.991; sensitivity, 97%; specificity, 90%) in deviation map showed a higher diagnostic performance (p = 0.002) than the best circumpapillary RNFL parameter (inferior RNFL thickness; AUC, 0.914; sensitivity, 79%; specificity, 92%). For diffuse defects, there was no significant difference between the RNFL deviation map and circumpapillary RNFL parameters. In mild glaucoma with localized defect, RNFL deviation map showed a better diagnostic performance than circumpapillary RNFL measurement. Conclusions. RNFL deviation map is a useful tool for evaluating glaucoma regardless of localized or diffuse defect type and has advantages over circumpapillary RNFL measurement for detecting localized RNFL defects.

The Effect of Optic Disc Center Displacement on Retinal Nerve Fiber Layer Measurement Determined by Spectral Domain Optical Coherence Tomography.

PURPOSE: To investigate the effect of optic disc center displacement on retinal nerve fiber layer (RNFL) measurement determined by spectral domain optical coherence tomography (SD-OCT). METHODS: The optic disc center was manipulated at 1-pixel intervals in horizontal, vertical, and diagonal directions. According to the manipulated optic disc center location, the RNFL thickness data were resampled: (1) at a 3.46-mm diameter circle; and (2) between a 2.5-mm diameter circle and 5.4-mm square. Error was calculated between the original and resampled RNFL measurements. The tolerable error threshold of the optic disc center displacement was determined by considering test-retest variability of SD-OCT. The unreliable zone was defined as an area with 10% or more variability. RESULTS: The maximum tolerable error thresholds of optic disc center displacement on the RNFL thickness map were distributed from 0.042 to 0.09 mm in 8 directions. The threshold shape was vertically elongated. Clinically important unreliable zones were located: (1) at superior and inferior region in the vertical displacement; (2) at inferotemporal region in the horizontal displacement, and (3) at superotemporal or inferotemporal region in the diagonal displacement. The unreliable zone pattern and threshold limit varied according to the direction of optic disc displacement. CONCLUSIONS: Optic disc center displacement had a considerable impact on whole RNFL thickness measurements. Understanding the effect of optic disc center displacement could contribute to reliable RNFL measurements.

Retinal Nerve Fiber Layer Thickness Measurement Repeatability for Cirrus HD-OCT Retinal Tracking System During Eye Movement.

PURPOSE: To investigate the repeatability of peripapillary retinal nerve fiber layer (RNFL) thickness measurements obtained using Cirrus high-definition optical coherence tomographic (Cirrus HD-OCT) retinal tracking system during various types of eye movements. MATERIALS AND METHODS: We included 20 healthy eyes, 40 glaucomatous eyes of elderly patients, and 17 eyes with pathologic nystagmus. For healthy eyes, RNFL thickness measurements were obtained under 3 conditions: (1) without eye movement, fixated on the device's internal target, (2) with horizontal eye movement, and (3) with vertical eye movement during scan acquisition. Each session was performed 3 times with and without the use of the retinal tracking system. The repeatability of RNFL thickness measurements obtained with and without the retinal tracking was compared within each session and among the sessions. RESULTS: In healthy eyes, measurements obtained without the use of a retinal tracking system showed lower repeatability when measurements were obtained with eye movements than without (P<0.05). However, when retinal tracking system was used, measurement repeatability under conditions with eye movements was similar to that achieved without eye movement (P>0.05) and higher than that obtained without the use of a retinal tracking system (P<0.05). In elderly glaucomatous patients, the retinal tacking system did not significantly improve measurement repeatability during fixation (P>0.05). In eyes with pathologic nystagmus, the tracking system did not follow eye movement and scan acquisition was not processed. CONCLUSIONS: Cirrus HD-OCT retinal tracking system may enhance RNFL thickness measurement repeatability under certain, but not all, eye movement conditions.

Quantitative analysis of localized retinal nerve fiber layer defects using spectral domain optical coherence tomography.

PURPOSE: To compare the topographic features of localized retinal nerve fiber layer (RNFL) defects presented in red-free RNFL photography and spectral domain optical coherence tomography (SD-OCT), and to evaluate the correlation with structural and functional parameters. METHODS: Sixty eyes with localized RNFL defects in red-free RNFL photographs were included. RNFL thickness map and significance map were obtained by SD-OCT. The angular location, angular width, and area of localized RNFL defects were measured and compared among RNFL thickness map, significance map (red, <1% level; yellow, <5% level), and RNFL photograph. The RNFL defect areas were analyzed by their correlations with structural and functional parameters. RESULTS: The RNFL defect area of RNFL thickness map was significantly greater than those of red significance map, and smaller than those of RNFL photograph and yellow significance map (all P<0.001). RNFL thickness map showed a significantly narrower angular width than RNFL photograph and yellow significance map (all P<0.001). The area, angular width, and angular location of localized RNFL defects in RNFL photographs strongly correlated with those of RNFL thickness maps and significance maps (all r≥0.741, P<0.001). The relationship between RNFL defect area and structural-functional parameters was also significant. CONCLUSIONS: The high topographic correlations in RNFL defects between RNFL photography and SD-OCT RNFL maps suggest the validity of SD-OCT RNFL imaging for detecting localized glaucomatous RNFL damage. In addition, structural and functional parameters are closely related to RNFL defect areas. Quantitative measurements of RNFL defects might be valuable for glaucoma diagnosis.

Retinal nerve fiber layer defect volume deviation analysis using spectral-domain optical coherence tomography.

PURPOSE: To report the retinal nerve fiber layer (RNFL) defect volume deviation according to structural RNFL loss in RNFL thickness maps. METHODS: Retinal nerve fiber layer defect is defined in RNFL thickness maps by the degree of RNFL loss. A 20% to 70% degree of RNFL loss was set with a 1% interval as the reference level for determining the boundary of RNFL defects. Each individual RNFL thickness map was compared with a normative database map and the region below the reference level was identified as an RNFL defect. The RNFL defect volume was calculated by summing the volumes of each pixel inside RNFL defect. The RNFL defect volume deviation was calculated by summing the differences between the normative database and the subject's RNFL measurements. To evaluate the glaucoma diagnostic ability, the areas under the receiver operating characteristics curves (AUCs) were calculated. RESULTS: Retinal nerve fiber layer defect volume and RNFL defect volume deviation (0.984 and 0.986, respectively) had significantly greater AUCs than all circumpapillary RNFL thickness parameters (all P < 0.001). In the early stage of RNFL loss (under 31% loss of RNFL), RNFL defect volume deviation showed better diagnostic performance than the RNFL defect volume. In multivariate analysis, RNFL defect volume and RNFL defect volume deviation were significantly associated with the mean deviation in visual field tests. CONCLUSIONS: Retinal nerve fiber layer defect volume deviation is a useful tool for diagnosing glaucoma and monitoring RNFL change. In early stage of RNFL loss, RNFL defect volume deviation is more sensitive for detecting glaucoma than the RNFL defect volume measurements.

Diffuse retinal nerve fiber layer defects identification and quantification in thickness maps.

PURPOSE: To report retinal nerve fiber layer (RNFL) defect identification and quantification in RNFL thickness maps according to the structural RNFL loss, and to evaluate diffuse RNFL defects. METHODS: A total of 170 patients with glaucoma and 186 normal subjects were consecutively enrolled. We defined RNFL defects in an RNFL thickness map by the degree of RNFL loss. The reference level for RNFL defect determination was set as a 20% to 70% degree of RNFL loss with a 1% interval. To identify RNFL defects, each individual RNFL thickness map was compared to the normative database map by using MATLAB software, and the region below the reference level was detected. The area, volume, location, and angular width of each RNFL defect were measured. Diffuse RNFL defects were defined as having an angular width > 30°. RESULTS: The optimal reference level for glaucomatous RNFL defects identification was 42% loss of RNFL. Retinal nerve fiber layer defects were identified in all (100%) of the 170 glaucoma patients and false-positive RNFL defects were detected in 16 (8.16%) cases among the 186 normal subjects. In all, 64.1% of glaucoma patients had diffuse RNFL defects, and 47.7% of diffuse RNFL defects were associated with mild glaucoma patients. The volume of diffuse RNFL defects was significantly associated with the severity of glaucomatous damage (P = 0.009). Diffuse RNFL defects were located closer to the center of the optic disc than localized RNFL defects (P < 0.001). CONCLUSIONS: Retinal nerve fiber layer thickness map analysis is an effective method for analyzing RNFL defects. Quantitative measurements (area, volume, location, and width) were useful to understanding diffuse RNFL defects.

Retinal nerve fiber layer volume measurements in healthy subjects using spectral domain optical coherence tomography.

PURPOSE: To report retinal nerve fiber layer (RNFL) volume measurement using spectral domain optical coherence tomography (SD-OCT). We determined the characteristics and effecting factors of the RNFL volume in healthy eyes. METHODS: Eighty-six eyes from 86 healthy volunteers were included. All participants underwent 3D-disc scanning using SD-OCT. We developed a computer program using Matlab software to extract RNFL thickness values from colored topographic RNFL thickness map. Total average, quadrant, and clock-hour RNFL volume were automatically calculated between 2.5 and 5 mm diameter circles using the length, width, and height of each pixel derived from the RNFL thickness map. RESULTS: The mean total RNFL volume was 1.478±0.124 mm and RNFL volume profiles showed double-hump patterns. RNFL volumes of superior and inferior quadrants were significantly greater than those of temporal and nasal quadrants (all P<0.001). A strong correlation existed between RNFL volume and conventional circumpapillary RNFL thickness measured by built-in software (R=0.895 to 0.972). Image quality and age were associated with RNFL volume measurement. CONCLUSIONS: RNFL volume measurement from RNFL thickness map analysis provides an alternative approach to characterizing and evaluating RNFL. RNFL volume measurement may be valuable for the objective and quantitative evaluation of 3-dimensional RFNL changes.

TCCR/WSX-1 is a novel angiogenic factor in age-related macular degeneration.

PURPOSE: Age-related macular degeneration (AMD) is the major cause of blindness among persons aged 60 years and older. The current approved therapies for AMD are exclusively limited to inhibiting vascular endothelial growth factor. However, substantial improvement in vision occurs in only one-third of patients treated with vascular endothelial growth factor antagonists, and one-sixth of treated patients still progress to legal blindness. Therefore, more specific targets are needed to treat AMD. Our goal was to find secretory proteins that change in number in the aqueous humor and that cause exudative AMD disease. METHODS: The number of molecules changed in the aqueous humor of patients with AMD compared to the control group was determined using antibody array analysis. The levels of angiopoietin-2 and insulin-like growth factor binding protein-related protein 7 were measured using enzyme-linked immunosorbent assay. The levels of T-cell cytokine receptor (TCCR/WSX-1) were determined using western blot. Potential TCCR/WSX-1-mediated effects on tube formation as well as phosphorylation of extracellular signal-regulated kinase in human umbilical vein endothelial cells were determined. RESULTS: We found that the numbers of several molecules were changed in the aqueous humor of patients with AMD compared to the control group. Among them, angiopoietin-2 was reduced by 20% and TCCR/WSX-1 was increased twofold. Moreover, exogenous TCCR protein induced tube formation and phosphorylation of extracellular signal-regulated kinase in human umbilical vein endothelial cells. CONCLUSIONS: Our study suggests that TCCR/WSX-1 is closely associated with angiogenesis and could serve as a novel therapeutic target in patients with AMD.

Optic disc pit with peripapillary retinoschisis presenting as a localized retinal nerve fiber layer defect.

A 59-year-old woman was referred to our clinic for a glaucoma evaluation. The visual acuity and intraocular pressure were normal in both eyes. However, red-free fundus photography in the left eye showed a superotemporal wedge-shaped retinal nerve fiber layer defect, and visual field testing showed a corresponding partial arcuate scotoma. In an optical coherence tomography examination, the macula was flat, but an arcuate-shaped peripapillary retinoschisis was found. Further, the retinoschisis seemed to be connected with a superotemporal optic pit shown in a disc photograph. After 3 months of a topical prostaglandin analogue medication, the intraocular pressure in the retinoschisis eye was lowered from 14 to 10 mmHg and the peripapillary retinoschisis was almost resolved. We report a rare case of an optic disc pit with peripapillary retinoschisis presenting as a localized retinal nerve fiber layer defect.

A case of optic nerve atrophy with severe disc cupping after methanol poisoning.

We report a rare case of optic nerve atrophy with severe disc cupping resulting from methanol poisoning. A 30-year-old man presented to the hospital complaining of decreased visual acuity in both eyes a day after drinking alcohol containing methanol. His initial visual acuity allowed for only visualizing hand motion and not corrected in either eye. Initial intraocular pressure was within normal limits in both eyes. Initial fundus examination showed optic disc swelling in both eyes. Four years later, he visited our hospital for an eye evaluation. Visual acuity in both eyes still only allowed for visualizing hand motion. No nystagmus was observed in either eye during the optokinetic nystagmus test, and no waves were found in a visual evoked potential test. No specific change was noted on brain magnetic resonance imaging. On fundus examination, there was disc pallor in both eyes and disc cupping with a high cup/disc (C/D) ratio above 0.9 in the left eye. C/D ratio of the right eye was 0.5. Methanol poisoning may induce glaucomatous disc cupping in the late stage as well as optic atrophy. One possible mechanism of disc cupping is ganglion cell loss due to acute demyelination of the retrobulbar optic nerve. This report is the first photographic evidence of methanol induced optic disc cupping in Korea.

Comparison of glaucomatous optic nerve damage in primary angle-closure glaucoma with and without acute attack.

PURPOSE: To compare the glaucomatous optic nerve damage in primary angle-closure glaucoma (PACG) with acute attack (acute PACG; AACG) and PACG without acute attack (chronic PACG; CACG). METHODS: The study subjects were 84 normal individuals, 130 AACG patients, and 86 CACG patients. Color optic disc photographs were evaluated for the presence or absence of 10 qualitative signs to differentiate between normal and glaucomatous optic discs. RESULTS: Abnormally shaped rim width (alteration of ISN'T rule), bared circumlinear vessel, vessel bayonetting, rim width narrower than the temporal sector, and zone beta (nasal and superotemporal sectors) were detected more frequently in the CACG group than in the AACG group (P<0.05). The most accurate qualitative sign was abnormally shaped rim width in both groups. The specificity and sensitivity of abnormally shaped rim width were 71.4% and 60.8% for AACG, and 71.4% and 81.4% for CACG, respectively. CONCLUSIONS: The optic disc damage is greater in CACG than in AACG.