Knowledge of medications among patients with glaucoma in Taiwan.

BACKGROUND/PURPOSE: To investigate the knowledge and learning ability of glaucoma patients regarding their anti-glaucoma topical medications. METHODS: Patients on regular follow-up at the Glaucoma Clinic at Hsin-Chu General Hospital were recruited. After detailed ocular examinations, the participants were asked to recall and identify their glaucoma eye drops. The same test was repeated 3 months later. The results of both tests, the learning ability of patients regarding their glaucoma drugs, and the relationship between learning ability and demographic variables were evaluated. RESULTS: Two hundred eighty-seven glaucoma patients participated in this study. Of the study population, 25.8% and 57.1% could recall their topical mediation at the first and second tests, whereas 72.1% and 88.5% could identify their prescribed eye drops at the first and second tests, respectively. Approximately 34% of the participants showed improved knowledge at the repeat test, whereas 40% of the participants showed no improvement. Participants with a better learning ability were more likely to be younger, with a higher level of education, and with less visual field impairment. CONCLUSION: The knowledge of glaucoma patients regarding their prescribed medication was deficient in Taiwan. Physician effort could improve knowledge on the prescribed drugs. Patient-centered education should be considered, targeting elderly individuals, illiterate individuals, and those with loss of visual function to increase compliance with glaucoma medication.

A nine-year population-based cohort study on the risk of multiple sclerosis in patients with optic neuritis.

Patients with optic neuritis (ON) are at an increased risk of developing multiple sclerosis (MS), an illness that may result in physical dysfunction and short life expectancy. Information on the conversion rate to MS of patients with ON is essential in determining the impact of ON on the incidence of MS. Previous Taiwanese studies on the risk of MS in patients with ON were all hospital based, thereby limiting the generalizability of the findings. We aimed to estimate the risk of MS in patients with ON using a nationally representative sample. A cohort of 2,741 patients who sought outpatient care for ON in 2000 was identified from Taiwan's National Health Insurance claims. The control group consisted of 27,330 age- and sex-matched subjects randomly selected from all beneficiaries in 2000. The person-year approach with Poisson assumption was used to estimate the incidence rate of MS from 2000 to 2008. The relative risk of outpatient visit or hospitalization for MS was estimated using the Cox proportional hazard model. The incidence rates of MS in the ON and control groups were 25.6 and 0.4, respectively, per 10,000 person-years; these values represent a relative risk estimate of 30.84 (95% confidence interval: 14.48 to 65.73) after the potential confounders were considered. Female or younger patients with ON were associated with a significantly elevated risk of developing MS. This study found that Taiwanese patients with ON are at a substantially high relative risk of developing MS. In addition to patients with ON, female and younger people should also receive intensive neurological care to further reduce their risk of developing MS.

Peripapillary choroidal neovascularization associated with optic nerve sheath meningioma.

Peripapillary choroidal neovascularization (PPCNV), a rare presentation of optic nerve sheath meningioma (ONSM), is associated with various ocular pathologies. Herein, we report a case with characteristics of age-related macular degeneration, PPCNV, optic disc edema, and a retinal-choroidal venous collateral. In addition to the recognition of an orbital base ONSM, magnetic resonance imaging revealed a distended perioptic subarachnoid space with the accumulation of cerebrospinal fluid anterior to the tumor. On the basis of these clinical findings, we postulated the pathogenesis of PPCNV-associated ONSMs.

Simvastatin upregulates Bcl-2 expression and protects retinal neurons from early ischemia/reperfusion injury in the rat retina.

Simvastatin has been shown to enhance the survival of retinal ganglion cells (RGCs) following ischemia-reperfusion (IR) injury by mediating the expression of stress proteins. The purpose of this study was to investigate the effect of simvastatin on retinal neurons and the expression of apoptotic proteins in a rat IR model. Wistar rats received intravitreal injection of simvastatin immediately after retinal reperfusion. Retinal ischemia was induced by increasing intraocular pressure to 150 mm Hg for 60 min. The number of viable RGCs was measured after retrograde labeling with Fluoro-Gold. Ischemia-induced apoptotic cell death was studied using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). We found that simvastatin treatment enhanced RGC survival after retinal ischemia by approximately 40% and decreased retinal neuronal apoptosis. Using western blot analysis, we found that simvastatin upregulated the expression of Bcl-2 in the retina. In contrast, the level of the protein Bax was unaffected by simvastatin treatment. Our results suggest that RGC loss induced by retinal IR may be prevented by simvastatin and that the mechanism underlying this process possibly involves an alteration in the apoptotic pathway.

A Comparison of Optic Neuritis in Asian and in Western Countries.

Acute demyelinating optic neuritis is a common optic neuropathy in young adults. There is usually satisfactory visual recovery. However, some patients convert to multiple sclerosis (MS) with potential sequelae of neurological disability. The Optic Neuritis Treatment Trial in the United States was conducted prospectively for 15 years and provided valuable data about clinical course, efficacy of steroid treatment, and risk of conversion to MS. Compared to the many studies in Western countries, research concerning optic neuritis in Asia has so far not been extensive. However, cumulative evidence shows that various features of this disorder differ between patients of Caucasian and Oriental descent. In this article we review up-to-date studies on optic neuritis in Asia and compare the results with prior literature. Prospective and multi-centre studies are currently underway in these regions to increase our understanding of optic neuritis in Asia.

Metronidazole-Induced Irreversible Optic Neuropathy.

Metronidazole-induced optic neuropathy is a rare complication. Most patients have excellent visual recovery. In this study, we report a patient who presented with a sudden onset of severe visual loss after a 1-week course of metronidazole. Myelitis developed simultaneously. The vision and the accompanying neurological deficiency of the patient did not improve even after metronidazole was discontinued immediately and various treatments were given.

Effects of epigallocatechin-3-gallate on rat retinal ganglion cells after optic nerve axotomy.

The purpose of this study was to investigate the effects of epigallocatechin-3-gallate (EGCG) in axotomized eyes and the pathways related to its action. Wistar rats received intracranial optic nerve (ON) axotomy 2 mm behind the globe in left eyes, whereas right eyes received sham operations. EGCG was administrated via intraperitoneal injection 30 min before and 4 days after axotomy. The density of retinal ganglion cell (RGC) was examined by a retrograde labeling technique. Western blot analysis was used to assess the expression of neuronal nitric oxide synthase (nNOS), Bax, Bcl-2, ERK and Akt. Optic nerve axotomy caused 54% RGC loss 7 days following surgery, and EGCG treatment reduced RGC loss by 12% (P = 0.017). The expression of the nNOS and pro-apoptotic Bax proteins were increased 5 days after axotomy, while EGCG treatment significantly blunted the up-regulation of the above two proteins (P = 0.04 and 0.02, respectively). Axotomy-induced p-ERK 1/2 and p-Akt proteins expression 5 days and 3 days following injury, respectively. Treatment with EGCG further enhanced p-ERK 1/2 and p-Akt expressions after axotomy. Inhibition of ERK and Akt pathways attenuated the protection of EGCG on RGC against axotomy damage. Thus, we demonstrated that administration of EGCG prior to axotomy promotes RGC survival. The neuroprotective capacity of EGCG appears to act through mediating nitric oxide, anti-apoptotic, and cell survival signaling pathways.

Giant cell (Temporal) arteritis with anterior ischemic optic neuropathy: a biopsy-proven case in Taiwan.

Giant cell arteritis with arteritic anterior ischemic optic neuropathy has rarely been diagnosed in Taiwan. Recently, we encountered a 76-year-old Taiwanese patient who presented with right visual impairment and marked pale swelling of his right disc. He also suffered body weight loss, general malaise and many typical manifestations of giant cell arteritis, such as jaw claudication, a tender, non-pulsating engorgement of his temporal arteries, and a highly elevated erythrocyte sedimentation rate and C-reactive protein level. Biopsy of his right superficial temporal artery revealed a granulomatous inflammation with multinucleated giant cell infiltration. This was a biopsy-proven case of giant cell arteritis with arteritic anterior ischemic optic neuropathy and indicated that although rare, this disease could occur in patients in Taiwan.

Acute zonal occult outer retinopathy presenting as optic neuritis.

Acute zonal occult outer retinopathy (AZOOR) is an outer retinal disorder characterized by the acute loss of visual functions. Herein, we report a case of AZOOR presenting features mimicking optic neuritis. A 17-year-old healthy male reported fogginess in the right eye for 2 weeks. His best-corrected visual acuity was 20/20 in both eyes. Results of a color vision test and pupillary reaction were unremarkable. Funduscopic examination revealed a subtle hyperemic disc surrounded by hyperpigmentation in the right eye. Visual field examination confirmed an enlarged blind spot in the affected eye. Fundus autofluorescence imaging revealed zonal hyperautofluorescence around the optic disc. Fluorescein angiography showed optic disc staining and a window defect in the retinal pigment epithelium. Optical coherence tomography demonstrated loss of the ellipsoid line at the corresponding hyperautofluorescent region. All these characteristics indicated a diagnosis of AZOOR. However, the prolonged P100 wave observed through visual-evoked potential examination, hyperintensity T2 signal at the retrobulbar optic nerve through magnetic resonance imaging, and mild hyperemic optic disc along with optic disc staining through fluorescein angiography resemble the characteristics of optic neuritis. Because the clinical features of AZOOR are similar to those of optic neuritis, ophthalmologists should be able to differentiate between these two diseases to achieve a timely and correct diagnosis.

Novel role for the delta-opioid receptor in hypoxic preconditioning in rat retinas.

Delta-opioid receptor (DOR) is an oxygen-sensitive protein whose function in the rat retina is unknown. We examined whether DOR is involved in hypoxic preconditioning (HPC)-mediated retinoprotection following intraocular pressure (IOP) elevation. Rats were exposed to intermittent hypoxia (10% oxygen) to induce HPC. Unilateral retinal ischemia/reperfusion injury was induced by elevating IOP to 100 mmHg for 1 h. HPC attenuated the loss of neuronal marker expression and increased pro-apoptotic caspase 3 activity in the IOP retina. Excess superoxide production and 8-iso-prostaglandin F2alpha accumulation caused by enhanced oxidant protein expression and reduced antioxidant enzyme level after IOP elevation were largely abrogated by HPC. HPC markedly increased the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and DOR, but intravitreal administration of HIF-1alpha-specific small interfering RNA abrogated the up-regulation of DOR. This suggested that DOR functions downstream of HIF-1alpha. However, the endogenous content of leucine enkephalin in retinas was not affected by HPC or IOP. Treatment of retinas with the DOR antagonist naltrindole attenuated the HPC-induced protection and activation of extracellular signal-regulated kinase. These results suggest a novel mechanism of HPC-mediated retinoprotection whereby HIF-1alpha induces the expression of DOR, and DOR-mediated activation of extracellular signal-regulated kinase triggers cellular events that correct the redox imbalance in the post-ischemic retina.

Bevacizumab is not toxic to retinal ganglion cells after repeated intravitreal injection.

PURPOSE: The cytotoxicity of single and repeated administration of bevacizumab to retinal ganglion cells was studied in vivo and in vitro. METHODS: Rats received single or repeated injections of 125 microg of bevacizumab into the vitreous cavity of the left eye, while saline was injected into the right eye as a control. In the repeated injection group, bevacizumab was injected at the same concentration once per week for 4 weeks. Retinal ganglion cells were retrogradely labeled with Fluorogold dye, and counted after kill at 0 and 6 months after treatment. In the in vitro study, PC12 cells were cultured in various concentrations of bevacizumab (0, 1, 2, 5, and 10 mg/mL) to model retinal ganglion cells exposure. Cell viability in each group was assessed by an MTT assay. RESULTS: There was no significant difference in retinal ganglion cell numbers between control and bevacizumab-treated eyes following either single or repeated injection, or did bevacizumab have any significant influence on PC12 cell viability in vitro. CONCLUSION: These results suggest that intravitreal injection of bevacizumab poses no risk to retinal ganglion cells, even after repeated application.

Factors associated with retinal screening among patients with diabetes in Taiwan.

PURPOSE: The purpose of this study is to explore the factors associated with having a diabetic retinopathy exam (DRE) during the past 2 years among patients with diabetes. METHODS: Patients visiting the eye clinic at Shin-Kong Memorial Hospital in Taipei were enrolled in this study from January to June 2009. A total of 313 patients participated in this study. Excluding patients with missing responses for more than three questions (38) yielded a final sample of 275 participants. Chi-square and Mann-Whitney U-tests were used for bivariate analysis. Multivariable logistic regression examined factors associated with having a DRE controlling for demographic and health factors. RESULTS: Although 83% of participants said that their physician suggested DRE, only 60% were screened during the past 2 years. In response to the question about why patients did not seek a DRE exam, 43.2% reported that they did not know having this exam was necessary. In adjusted results, receiving information about the relationship between diabetes and retinopathy from medical staff and believing that diabetes could damage the vision were associated with having a DRE in the past 2 years (both P < 0.05). CONCLUSIONS: Although most patients indicated that their physician suggested the need for eye care, a substantial percentage of patients with diabetes were not aware of the need for a regular DRE. Information about the relationship between diabetes and retinopathy and concerns about damage to vision were associated with greater likelihood of seeking a DRE. These factors should be considered to promote DR screening.

Haem oxygenase-1 gene transfer protects retinal ganglion cells from ischaemia/reperfusion injury.

RGC (retinal ganglion cell) death following ischaemic insult is the major cause of a number of vision-threatening diseases, including glaucoma. The aim of the present study was to evaluate the role of HO-1 (haem oxygenase-1) in the retina against IR (ischaemia/reperfusion) injury. Adenovirus-mediated HO-1 gene transfer (Adv-HO-1) was carried out by injection into the vitreous body to induce HO-1 overexpression. At 3 weeks after transfection, levels of HO-1 expression, as measured by Western blot analysis, immunohistochemical staining and activity assay, were drastically up-regulated. Transient retinal ischaemia was induced by raising the intraocular pressure to 150 mmHg for 60 min. Untreated IR caused a significant decrease in RGC numbers at 3 and 7 days after reperfusion (76.1 and 67.2% of control eyes with sham IR respectively; P<0.001). Eyes pretreated with Adv-HO-1 had less RGC loss on day 3 and 7 following reperfusion compared with control eyes injected with Adv-GFP (adenovirus containing a gene for green fluorescent protein; 94.3 and 88.2% respectively; P=0.007 and 0.001). SnP (tin protoporphyrin), an HO-1 inhibitor, counteracted the effects of Adv-HO-1. In conclusion, these findings provide evidence that augmentation of HO-1 enzyme overexpression by intravitreal injection is able to protect RGCs against IR-induced damage.

Retinal nerve fiber layer thickness measured by optical coherence tomography in non-glaucomatous Taiwanese.

BACKGROUND/PURPOSE: Assessment of the peripapillary retinal nerve fiber layer (RNFL) is essential for neuroretinal diseases, especially for early prediction of glaucomatous damage. The purpose of this study was to measure RNFL thickness by Stratus optical coherence tomography (OCT) in normal Taiwanese subjects according to age group. METHODS: The thickness of the RNFL around the disc of normal subjects was obtained, after pupil dilation, by means of 3.4 mm diameter fast mode circle OCT scan. Data for one randomly selected eye of each subject were used for statistical analysis. Differences in RNFL thickness were determined by ANOVA. RESULTS: A total of 162 participants were evaluated: 61 male and 101 female, with mean age of 41.3 +/- 20 years (range, 6-74 years). Mean RNFL thickness was 108.7 +/- 9.4 micrometers (range, 85.5-133.7 micrometers). The RNFL was thickest in the inferior (135.8 +/- 16.3 micrometers) and superior (133.9 +/- 18.0 micrometers) quadrants, followed by the nasal (82.6 +/- 16.0 micrometers) and temporal (82.4 +/- 17.8 micrometers) quadrants (F = 551.9, p < 0.001). CONCLUSION: RNFL thickness was determined by OCT for a normal Taiwanese population aged 6-74 years. The normative data from this study may offer valuable information to enable comparisons of ocular diseases involving RNFL across different populations.

Age and axial length on peripapillary retinal nerve fiber layer thickness measured by optical coherence tomography in nonglaucomatous Taiwanese participants.

PURPOSE: This study investigates the influence of age and axial length (AL) on the peripapillary retinal nerve fiber layer (RNFL) thickness, as measured by optical coherence tomography (OCT). METHODS: Healthy patients visiting an eye clinic at a county hospital were recruited. All participants underwent comprehensive ophthalmologic examinations, and their retinas were scanned using 3D OCT-1000. In total, 223 patients with 446 eyes were included. The mean age and AL were 42.07 ± 13.16 (21-76) years and 25.38 ± 1.73 (21.19-30.37) mm, respectively. RESULTS: The average RNFL thickness decreased by 2.71 µm for every 10-year increase in age (P < 0.001). Age-related RNFL thinning was more significant in participants older than 41 years (-0.24µm/year; P = 0.015). The earliest sector showing a significant decline in RNFL thickness was after 35 years of age (-0.70µm/year; P = 0.011) at the superior quadrant and at the 1-2 o'clock hour (-1.42µm/year; P = 0.009). Meanwhile, the maximal rate of age-associated RNFL decay was observed in these two regions as well. The reduction of RNFL with age progression did not differ in eyes with long AL (> 27 mm; -0.16µm/year) or those with short AL (< 25 mm; -0.22µm/year). For every 1-mm-greater AL, RNFL was thinner by 1.78 µm (P < 0.001). The inferior quadrant showed the greatest tendency of RNFL decline with longer AL (4.46 µm/mm; P < 0.001). CONCLUSIONS: The factors of age and AL should be considered when interpreting the results. Significantly age-associated RNFL thinning was found in participants older than 41 years. Reduction of RNFL thickness with increasing age was not affected by AL. Topographic variations in RNFL thinning were observed in that the maximal decline of RNFL thickness with advancing age at the superior quadrant whereas with elongation of AL at the inferior quadrant.

Dynamic changes in reactive oxygen species and antioxidant levels in retinas in experimental glaucoma.

We investigated the balance of free radicals in retinas at various time points after chronically elevating intraocular pressures in rats. The left eyes of female Wistar rats were divided into five intraocular pressure elevation (IOPE) subgroups after cauterization of three episcleral veins (1 day, 3 days, 1 week, 3 weeks, and 5 weeks) and time-related sham controls. Chemiluminescence levels were examined in isolated retinas. The nitroblue tetrazolium (NBT) incubation method was also performed to confirm the superoxide expression. The activities of antioxidant enzymes and lipid peroxides in isolated retinas were detected by spectrophotometry. In the IOPE group, the intraocular pressure after cauterization was around 22-30 mm Hg; chemiluminescence levels of isolated retinas were significantly elevated on day 3 and week 1; there were more NBT-positive retinal ganglion cells on day 1 and day 3; lipid peroxidation also increased significantly from day 1 and came back to the baseline on week 5; the activities of superoxide dismutases and catalase rose on week 1. Intraocular pressure elevation was shown to change the free radical balance. We suggest that free radicals and their oxidative stresses may play a role in the early stage of glaucoma in causing retinal ganglion cell death in our rat model.

Optic disc size and other parameters from optical coherence tomography in Vietnamese-Americans.

PURPOSE: To investigate the optic disc parameters by optical coherence tomography (OCT) in Vietnamese with various types of glaucoma. PATIENTS AND METHODS: Medical charts of Vietnamese and White patients within a single practice were reviewed. Disc and rim areas by OCT were compared among nonglaucoma controls, different types of glaucoma, and glaucoma suspect. The association of these parameters with demographic and ocular features was evaluated. RESULTS: Data from 1416 Vietnamese and 57 White patients were included. A larger mean disc area was observed in eyes with primary angle-closure glaucoma than in eyes with primary angle-closure and primary angle-closure suspect (both P<0.001). There was no association between disc size with central corneal thickness (P=0.051) and sex (P=0.155). Vietnamese patients with glaucoma and glaucoma suspicion had larger discs than diagnosis-matched Whites (P=0.043 and 0.021, respectively). CONCLUSIONS: Vietnamese patients with glaucoma seem to have larger optic discs than White patients. Central corneal thickness had no association with disc area in this study population.

Glaucoma and clinical characteristics in Vietnamese Americans.

PURPOSE: To assess the proportions of glaucoma types and clinical characteristics in Vietnamese Americans in a single-center, retrospective study. METHODS: Medical charts of Vietnamese-American patients who visited a single private practice in Northern California from 1998-2007 were reviewed. The main outcome measures included the distribution and characteristics of glaucoma types, and clinical parameters associated with the presence of various glaucomas. RESULTS: Data from 2247 patients aged 18-98 years were reviewed. Glaucoma was determined for 305 patients (13.6%). Among this group, 54.8% had primary open-angle glaucoma (POAG), 26.9% had primary angle-closure glaucoma (PACG), 13.4% had mixed mechanism glaucoma (MMG), and 4.9% had secondary glaucoma. In the MMG group (41 patients), 27 patients who initially had open angles developed narrow angles and underwent laser peripheral iridotomy (LPI) with a mean follow up of 6.4 years from the time of iridotomy. The other 13 patients had glaucoma progression with open angles after LPI. One POAG patient had neovascular glaucoma due to retinal vein occlusion several years later. Compared to the PACG group, the MMG group had significantly lower baseline intraocular pressure (25.0 vs. 20.2 mmHg, p = 0.007) but with no difference in biometry. CONCLUSIONS: POAG is the major type of glaucoma in this clinic-based Vietnamese population. However, Vietnamese appear to have a relatively higher proportion of PACG than Caucasians and those of African descent. It is recommended that gonioscopy be part of the regular eye check-up for adult Vietnamese patients.

Long-term outcomes of laser iridotomy in Vietnamese patients with primary angle closure.

BACKGROUND/AIMS: To investigate the long-term outcomes of laser peripheral iridotomy (LPI) on controlling intraocular pressure (IOP) and progression of angle closure in Vietnamese. METHODS: Medical charts of Vietnamese patients who were diagnosed as having primary angle-closure suspect (PACS), primary angle closure (PAC) or primary angle-closure glaucoma (PACG), and who had received LPI at least 10 years prior, in a single private practice were reviewed. The main outcomes included use of further treatments after LPI, progression rate to another classification category and ocular characteristics associated with progression. RESULTS: 359 patients with a mean follow-up period of 11.8 ± 1.6 years after the LPI were included in this study. The proportion of patients who required additional therapies (medical, laser or surgical) to control IOP were 7.1, 42.4 and 100% in the PACS, PAC and PACG groups, respectively. Fifty-three patients with PACS (22.2%) progressed to PAC; nine patients with PACS (3.8%) progressed to PACG; and five PAC patients (5.2%) progressed to PACG. Cataract surgery was a significant factor associated with PACS eyes without progression (p=0.019). CONCLUSIONS: Further medications, laser or surgery are frequently required to control IOP after LPI for eyes with PAC, especially for eyes with PACG. Lens extraction seems to play a protective role in PACS eyes. Close follow-up after LPI remains necessary to prevent progression of disease.