Hyoung Won Bae

Systemic Hypertension as a Risk Factor for Open-Angle Glaucoma: A Meta-Analysis of Population-Based Studies

Background/Aims Systemic hypertension is thought to increase the risk for developing open-angle glaucoma (OAG) through several mechanisms. However, previous epidemiological studies have shown conflicting results regarding this potential association. We systematically evaluated this issue by conducting a meta-analysis of population-based studies. Methods A comprehensive search for articles published before 31 March 2014 was performed using PubMed, Embase, and reference lists. The pooled odds ratio (OR) was calculated using the fixed- and random-effects models, and meta-regression was performed according to age. Subgroup analyses were also conducted, and publication bias was assessed using a funnel plot and Egger’s regression test. Results This meta-analysis included 16 studies involving 60,084 individuals, with substantial homogeneity among the studies. The pooled OR for OAG was 1.22 (95% confidence interval, CI: 1.09–1.36) using the fixed-effects model and 1.22 (95% CI: 1.08–1.37) using the random-effects model in all included studies. For subgroup analyses, the pooled OR for high-tension glaucoma (HTG) was higher than that for normal-tension glaucoma (NTG) (OR = 1.92 and 0.94, respectively). No significant difference was detected between Asian and Western populations, and no publication bias was detected in either analysis. Conclusions Systemic hypertension increases the risk for developing OAG, especially in those with HTG.

Estimated Trans-Lamina Cribrosa Pressure Differences in Low-Teen and High-Teen Intraocular Pressure Normal Tension Glaucoma: The Korean National Health and Nutrition Examination Survey.

Background To investigate the association between estimated trans-lamina cribrosa pressure difference (TLCPD) and prevalence of normal tension glaucoma (NTG) with low-teen and high-teen intraocular pressure (IOP) using a population-based study design. Methods A total of 12,743 adults (≥ 40 years of age) who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) from 2009 to 2012 were included. Using a previously developed formula, cerebrospinal fluid pressure (CSFP) in mmHg was estimated as 0.55 × body mass index (kg/m2) + 0.16 × diastolic blood pressure (mmHg)—0.18 × age (years)—1.91. TLCPD was calculated as IOP–CSFP. The NTG subjects were divided into two groups according to IOP level: low-teen NTG (IOP ≤ 15 mmHg) and high-teen NTG (15 mmHg < IOP ≤ 21 mmHg) groups. The association between TLCPD and the prevalence of NTG was assessed in the low- and high-teen IOP groups. Results In the normal population (n = 12,069), the weighted mean estimated CSFP was 11.69 ± 0.04 mmHg and the weighted mean TLCPD 2.31 ± 0.06 mmHg. Significantly higher TLCPD (p < 0.001; 6.48 ± 0.27 mmHg) was found in the high-teen NTG compared with the normal group. On the other hand, there was no significant difference in TLCPD between normal and low-teen NTG subjects (p = 0.395; 2.31 ± 0.06 vs. 2.11 ± 0.24 mmHg). Multivariate logistic regression analysis revealed that TLCPD was significantly associated with the prevalence of NTG in the high-teen IOP group (p = 0.006; OR: 1.09; 95% CI: 1.02, 1.15), but not the low-teen IOP group (p = 0.636). Instead, the presence of hypertension was significantly associated with the prevalence of NTG in the low-teen IOP group (p < 0.001; OR: 1.65; 95% CI: 1.26, 2.16). Conclusions TLCPD was significantly associated with the prevalence of NTG in high-teen IOP subjects, but not low-teen IOP subjects, in whom hypertension may be more closely associated. This study suggests that the underlying mechanisms may differ between low-teen and high-teen NTG patients.

Visual fields and OCT role in diagnosis of glaucoma.

Purpose To evaluate the clinical performance of visual field (VF) tests and optical coherence tomography (OCT) in diagnosing glaucoma. Methods One hundred sets of disc photographs, red-free fundus photographs, VF tests, and OCT images were presented progressively to seven ophthalmologists. Each set was provided in three steps: (1) the disc and red-free fundus photographs were shown first; (2) then, VF tests were also provided; and (3) finally, the OCT results were provided. The same process was repeated on another day. Kappa statistics were used to assess the intraobserver and interobserver agreement, as well as the agreement with the reference standard. Results The intraobserver agreement was almost perfect in this study and did not change markedly with the addition of diagnostic tools. The interobserver agreement increased from 0.54 to 0.61 when VF was added and increased slightly to 0.63 with OCT. The agreement with the reference standard also increased significantly from 0.48 to 0.61 after adding VF and increased slightly with additional OCT. Conclusions An optic disc evaluation and VF test are sufficient to diagnose glaucoma in most cases. However, OCT can play an important role in detecting glaucoma in cases in which it cannot be identified by optic disc examination and VF.

Vascular and metabolic comorbidities in open-angle glaucoma with low- and high-teen intraocular pressure: a cross-sectional study from South Korea

To assess the associations between vascular and metabolic comorbidities and the prevalence of open‐angle glaucoma (OAG) with low‐teen and high‐teen intraocular pressure (IOP) in Korea.

Repeatability and Agreement of Swept Source and Spectral Domain Optical Coherence Tomography Evaluations of Thickness Sectors in Normal Eyes.

Purpose of the Study: The purpose of the study was to evaluate the clinical efficacy of swept-source optical coherence tomography (SS-OCT), we compared the intradevice repeatability of thickness measurements obtained using SS-OCT to that of measurements obtained using spectral domain OCT (SD-OCT), and assessed the interdevice agreement of thickness measurements. Materials and Methods: This cross-sectional prospective study involved 3 consecutive measurements of peripapillary retinal nerve fiber layer (PP-RNFL) and ganglion cell-inner plexiform layer thickness in healthy subjects, using 2 different OCT systems. Intraclass correlation coefficients (ICCs) and coefficients of variability were calculated and compared for repeatability and agreement between study groups. Intradevice ICCs for each OCT system were compared, and Bland-Altman plots were used to evaluate their agreement. Results: Fifty-eight eyes from 58 healthy subjects (25 men and 33 women) were analyzed. SS-OCT images yielded larger PP-RNFL thickness values than SD-OCT images in every sector examined. In contrast, SD-OCT images yielded larger macular ganglion cell-inner plexiform layer thickness values than SS-OCT images. For SS-OCT, intradevice ICCs were ≥0.9 for all sectors. However, for SD-OCT, the 3 PP-RNFL measurement sectors had correlation coefficients <0.9. Interdevice ICCs varied more and were lower than intradevice values, because thickness measurement values differed between the OCT devices. Conclusions: Measurements differed between systems even for the same subject. SS-OCT had an intradevice repeatability similar to that of SD-OCT. These findings support the clinical application of SS-OCT.

Frequency, Type and Cause of Artifacts in Swept-Source and Cirrus HD Optical Coherence Tomography in Cases of Glaucoma and Suspected Glaucoma

ABSTRACT Purpose: To evaluate and compare the frequency, type and cause of imaging artifacts incurred when using swept-source optical coherence tomography (SS OCT) and Cirrus HD OCT in the same patients on the same day. Materials and methods: From left eye OCT results of 72 patients, disc area and macular area data could be compared between the two types of OCT. For each scan, the final printout report and source data were examined. For comparison between the two types of OCT, only source image data were used because of differences in the final printout report format. Results: There were no significant differences in the artifact frequencies between the two groups in either area (disc area: 35.9% of SS OCT, 42.2% of Cirrus OCT, p = 0.523; Macular area: 24.2% of SS OCT, 22.7% of Cirrus OCT, p = 1.00). The overall results of artifact comparison between the two types of OCTs also showed no significant differences. Boundary misidentification was the most common type of artifact observed, and ocular pathology was the most common cause of artifact in both types of OCTs. Among ocular pathologies, the epiretinal membrane (ERM) was the most common cause of OCT artifact production in both types of OCTs. Conclusions: There was no significant difference in the frequency, type and cause of artifacts between SS OCT and Cirrus HD OCT. Artifacts in OCT can influence the interpretation of OCT results. In particular, ERM around the optic disc could contribute to OCT artifacts and should be considered in glaucoma diagnosis or during patient follow-up using OCT.

Intravitreal Bevacizumab for the Treatment of Optic Disc Edema in a Patient with POEMS Syndrome.

Dear Editor, Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare multisystem disorder of obscure etiology that is associated with plasma cell dyscrasia [1]. Optic disc edema (ODE) has been reported to be a common ocular manifestation of POEMS syndrome [2]. Vascular endothelial growth factor (VEGF) has been regarded to have an important role in the pathophysiology of POEMS syndrome. We present a case of a young female patient presenting with bilateral optic nerve head edema after being diagnosed with POEMS syndrome, who was successfully treated with repeated intravitreal bevacizumab injections. The study protocol was approved by the Institutional Review Board of Yonsei University Severance Hospital and followed the tenets of the Declaration of Helsinki. A 34-year-old female patient presented with progressive narrowing of her visual field (VF). She had been diagnosed with POEMS syndrome 3 months previously at the department of hemato-oncology and had received palliative radiotherapy of 5,000 cGy to her right iliac crest, in which a plasmacytoma was located. She was also prescribed thalidomide 100 mg/day orally. According to her medical records, she had bilateral ODE at the time of diagnosis. At that time, lumbar puncture had revealed a slightly increased intracranial pressure of 16.18 mmHg. Her best-corrected visual acuity and intraocular pressure were 20 / 25 and 18 mmHg, respectively. There were no abnormal findings in either eye, with the exception of severe bilateral ODE. Automated perimetry showed bilateral enlarged blind spots and VF constriction. A fluorescein angiogram revealed early, well delineated hyperfluorescence in both optic discs, compatible with ODE (Fig. 1A-1H). Indocyanine green angiography revealed no abnormalities of choroidal perfusion. Fig. 1 Fundus photographs, fluorescein angiograms, and Humphrey automated perimetry (HAP) before and 3 months after the last intravitral bevacizumab Injection. (A,B) Bilateral fundus photographs showing optic nerve head edema (ODE). The disc is congested and ... Although her central vision was largely unaffected, the patient complained of progressively enlarging VF defects, which was confirmed by automated perimetry. The worsening VF defects coupled with the presence of ODE following the completion of radiotherapy warranted further intervention. Bilateral intravitreal bevacizumab injections were performed after informed consent had been obtained. Quantification of the intravitreal VEGF at the time of injection was within the established normal range (<30 pg/mL); however, the systemic VEGF level was elevated at 166.0 pg/mL (normal, 0 to 38.3 pg/mL). One week after the intravitreal injection of bevacizumab, repeat fluorescein angiogram and fundus photography revealed bilateral regression of the ODE accompanied by improvement in the VF. Approximately 50 days later, the patient complained of recurring VF defects, and increasing ODE was observed in both eyes. Repeat bilateral injections were administered with improvement in both the symptoms and ODE (Fig. 1I-1L). At follow-up 11 months after the injections, the patient had 20 / 20 vision with complete regression of the ODE, likely due to systemic improvement. The presence of ODE in POEMS syndrome has been well documented [2]. However, its etiology remains a matter of controversy. Increased systemic VEGF [3], increased intracranial pressure [4], nerve infiltration [5], and vascular hyperpermeability [4] have been suggested as possible causes. The patient presented here showed an initial improvement in symptomatic ODE after intravitreal bevacizumab injection; however, the ODE redeveloped approximately 50 days later. This timeline coincides with the known duration of anti-VEGF antibody. The successful management of ODE with anti-VEGF therapy before systemic improvement seems to imply that VEGF is an important component in the pathophysiology of ODE in POEMS syndrome. The lack of increase in VEGF titer from vitreous samples in our case coincides with data from previous report [3]. This suggests that ocular manifestations, such as ODE, are related to elevated level of systemic VEGF rather than intraocular VEGF. Systemic VEGF might alter optic nerve head vascular permeability via the choroidal blood flow, which is relatively free to communicate with the systemic circulation. We report a case of POEMS syndrome that was treated with intravitreal bevacizumab injection. Our findings suggest that the cause of ODE in POEMS syndrome might be associated with VEGF. A relationship between the cause of ODE in POEMS syndrome and systemic VEGF should be further investigated.

Increased stroke risk among patients with open-angle glaucoma: a 10-year follow-up cohort study

Background Although several studies showed the association between stroke and open-angle glaucoma (OAG), there is still lack of longitudinal studies based on large populations. Therefore, in this study, we investigated the risk of stroke after OAG diagnosis over a 10-year follow-up period. Methods We performed a retrospective nationwide propensity score-matched cohort study. OAG and comparison groups were selected from a large database from the Korean National Health Insurance Service, comprising 1 025 340 random subjects. The OAG group comprised patients with an initial diagnosis of OAG between January 2004 and December 2007 (n=1520), and the comparison group comprised randomly selected patients (five per glaucoma patient; n=7570). Each cohort was tracked until 2013 for stroke development. Cox proportional hazard regression analysis was performed to determine possible association Results OAG was associated with increased stroke incidence (HR=1.20, 95% CI 1.03 to 1.40). Hypertension, diabetes mellitus, chronic renal failure, atrial fibrillation, hyperlipidaemia, increasing age and male gender also increased the incidences of stroke. Risk of stroke for patients with OAG was greater in the older age group (≥65 years, HR=1.23, 95% CI 1.02 to 1.47) than in the younger age group (<65 years, HR=1.12, 95% CI 0.86 to 1.46), and greater in males (HR=1.31, 95% CI 1.06 to 1.60) than in females (HR=1.10, 95% CI 0.88 to 1.38). Conclusions Patients who were diagnosed with OAG were more likely to experience subsequent stroke than comparison group without OAG, and the risk was greater for older adults and males.

Comparison of three types of images for the detection of retinal nerve fiber layer defects.

Purpose To compare the clinical effectiveness of three types of images for detecting retinal nerve fiber layer (RNFL) defects. Methods Three image sets of 100 subjects (9 normal control subjects, 16 glaucoma suspects, and 75 glaucoma patients) were produced using color fundus photography, typical red-free RNFL photography, and blue reflectance RNFL photography with confocal scanning laser ophthalmoscopy (CSLO). A total of 300 images were rated twice in random order by five independent evaluators who were masked to the patient characteristics; each image was rated as normal, having a diffuse RNFL defect, or showing a wedge RNFL defect. Intraobserver and interobserver agreement, sensitivity, specificity, accuracy, and area under the curve were assessed. An additional analysis was performed for identifying differences in two black-and-white RNFL photographs. Results The results showed high intraobserver agreement, with relatively low interobserver agreements among the five evaluators. Blue reflectance RNFL photography with CSLO demonstrated the best performance in sensitivity, specificity, accuracy, and area under the curve. Blue reflectance RNFL images showed better accuracy than red-free RNFL images especially in subjects with wedge defects and in advanced glaucomatous cases. Conclusions The RNFL images produced using blue reflectance with CSLO showed the best performance for the detection of RNFL defects, especially in cases with wedge defects and advanced glaucoma stages.

Tear lipid layer thickness change and topical anti-glaucoma medication use

Purpose To investigate the effects of topical anti-glaucoma medications on tear lipid layer thickness (LLT) and the ocular surface. Methods This retrospective study examined ocular surface disease (OSD) subjects who had (n = 34) and who did not have (n = 51) open-angle glaucoma (OAG). OSD was evaluated with lipid layer thickness (using LipiView interferometer), tear breakup time (TBUT), total corneal and conjunctival staining (Oxford grading scale), and Ocular Surface Disease Index (OSDI). Four variables (total duration of anti-glaucoma medication use, duration of current anti-glaucoma medication use, total number of daily anti-glaucoma medication drops applied, and total number of anti-glaucoma medications [bottles]) related to anti-glaucoma medication were used to verify associations with LLT. Results Among the parameters, only LLT showed significantly lower values in the OAG group. In both groups, total staining showed a significant negative correlation between LLT and TBUT. Only in the OAG group, the OSDI showed significant correlations with number of medications (r = 0.389, p = 0.012) and daily number of drops (r = 0.354, p = 0.02); LLT showed significant correlations with TBUT (r = 0.381, p = 0.026) and total medication duration (r = −0.387, p = 0.013). In multivariate analyses, TBUT and total medication duration showed significant correlations with LLT (p = 0.032 and p = 0.015, respectively) in the OAG group. Conclusions Topically medicated OAG subjects with OSD had a lower tear LLT than those with OSD who did not have OAG. Therefore, our results indicate that one should evaluate ocular surface disease status in patients who take anti-glaucoma medications.