Short-term effect of atropine on higher-order aberrations in myopic children.

BACKGROUND: This study aimed to investigate the short-term effect of cycloplegia on higher-order aberrations (HOAs) in school-age myopic children who received 0.25% atropine for cycloplegic refraction. METHODS: We performed a retrospective chart review of 24 myopic children between the ages of 5 and 15 years, who had received one topical drop of 0.25% atropine for three consecutive nights before undergoing cycloplegic refraction. Auto-refraction, visual acuity, and HOAs measured with the iTrace aberrometer were compared before and after atropine use. To account for the effect of cycloplegia, the amount of HOAs under matching scanning sizes was compared. RESULTS: There were statistically significant differences in the spherical equivalent, with a hyperopic shift after atropine use (p < 0.001). Corrected visual acuity and spherical aberrations showed no significant change under the respective pupil and scanning sizes before and after atropine use. Under identical scanning sizes, there was a significant change in total spherical aberration (from 0.03 to 0.06 µm, p = 0.044) and internal spherical aberration (from -0.10 to -0.05 µm, p = 0.049) after atropine use. Differences in corneal spherical aberration were insignificant. CONCLUSION: The positive shift of spherical aberration induced by the inhibition of accommodation in myopic children may have a possible effect against myopic progression. Future studies can focus on the long-term effect on HOAs and impact on visual quality with lower concentrations of atropine.

Ambient Air Pollution and the Risk of Central Retinal Artery Occlusion.

PURPOSE: To investigate whether daily changes in ambient air pollution were associated with an increased risk of central retinal artery occlusion (CRAO). DESIGN: Retrospective population-based cohort study. PARTICIPANTS: We identified patients newly diagnosed with CRAO between 2001 and 2013 in a representative database of 1 000 000 patients that were randomly selected from all registered beneficiaries of the National Health Insurance program in Taiwan. We identified air pollutant monitoring stations located near these patients' residences in different administrative areas in Taiwan to determine the recorded concentrations of particulate matter ≤2.5 µm (PM2.5), particulate matter ≤10 µm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone (O3). Patients without corresponding monitoring stations were excluded. METHODS: We used a time-stratified case-crossover study design and conditional logistic regression analysis to assess associations between the risk of CRAO and the air pollutant levels in the days preceding each event. MAIN OUTCOME MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We enrolled 96 patients with CRAO in this study. The mean age was 65.6 years (standard deviation, 12.7 years) and 67.7% of patients were male. The risk of CRAO onset was significantly increased (OR, 1.09; 95% CI, 1.01-1.17; P = 0.03) during a 5-day period following a 1 part per billion increase in NO2 levels. After multipollutant adjustment, the increase in risk was most prominent after 4 days (OR, 1.40; 95% CI, 1.05-1.87; P = 0.02) to 5 days (OR, 2.16; 95% CI, 1.10-4.23; P = 0.03) of elevated NO2 levels in diabetic patients. The risk of CRAO onset also significantly increased in patients with hypertension and in patients ≥65 years old, after 1 day of elevated SO2 levels (OR, 1.88; 95% CI, 1.07-3.29; P = 0.03 and OR, 1.90; 95% CI, 1.13-3.21; P = 0.02, respectively). The transient concentration of the other air pollutants, including PM2.5, PM10, and O3, did not significantly affect the occurrence of CRAO in this study. CONCLUSIONS: These results demonstrated a positive association between air pollution and CRAO onset, particularly in patients with diabetes or hypertension and those older than 65 years.

Amiodarone-Associated Optic Neuropathy: A Nationwide Study.

PURPOSE: To investigate whether amiodarone use is associated with an increased risk of optic neuropathy. DESIGN: Retrospective population-based cohort study. PARTICIPANTS: Patients newly treated with amiodarone between 2005 and 2009 were identified from the Taiwan National Health Insurance Research Database. For each case patient, the study also included 4 age- and gender-matched control subjects who did not receive amiodarone treatment. METHODS: Cox multivariate regression analysis was used to assess the association between amiodarone and the occurrence of optic neuropathy. MAIN OUTCOME MEASURES: Hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The analysis included 6175 amiodarone-treated patients and 24 700 controls. The mean age was 66.7 years and 55.3% of subjects were male. The mean follow-up was 688 days. During the observational period, optic neuropathy developed in 17 amiodarone-treated patients (0.3%) and 30 control patients (0.1%; P = 0.006). Multivariate Cox regression analysis showed that amiodarone-treated patients had a 2-fold increased risk of optic neuropathy (HR, 2.09; 95% CI, 1.13-3.85; P = 0.02). After stratification by gender, amiodarone use remained a significant factor for optic neuropathy development among male subjects (HR, 3.05; 95% CI, 1.42-6.55; P = 0.004), but not among female subjects (HR, 1.15; 95% CI, 0.38-3.47; P = 0.81). Among amiodarone-treated patients, male gender was associated with a nearly 3-fold increased risk of optic neuropathy development compared with female gender (HR, 2.91; 95% CI, 0.94-9.01; P = 0.06). We also detected a trend of increased cumulative incidence of optic neuropathy with longer treatment duration (>41 vs. ≤41 days; HR, 3.46; 95% CI, 0.99-12.07; P = 0.05). However, higher daily dose did not increase the risk of optic neuropathy (HR, 0.96; 95% CI, 0.91-1.00; P = 0.07). CONCLUSIONS: These results demonstrated a higher risk of optic neuropathy in patients treated with amiodarone, especially in males and possibly in patients with longer duration of treatment.

Changes in Mitochondrial Morphology and Bioenergetics in Human Lymphoblastoid Cells With Four Novel OPA1 Mutations.

PURPOSE: Mutations in the optic atrophy 1 gene (OPA1) have been reported in patients with autosomal dominant optic atrophy (ADOA). OPA1 plays important roles in mitochondrial dynamics and cell apoptosis. The link between OPA1 mutations and changes in bioenergetics is still not fully resolved. The aim of this study was to investigate the effects of OPA1 mutations on the mitochondrial tubular network and bioenergetics. METHODS: We established lymphoblastoid cell lines from four ADOA families harboring different OPA1 mutations, unaffected relatives (internal control cell lines), and unrelated normal controls (normal control cell lines). OPA1 splice variants and mRNA were analyzed by reverse transcription-PCR and quantitative real-time PCR. Protein isoforms were examined by Western blotting. The mitochondrial network was visualized by confocal microscopy. Mitochondrial bioenergetics were assessed using a Seahorse XF24 flux analyzer. Mitochondrial membrane potential and oxidative damage were analyzed by flow cytometry. RESULTS: OPA1 mutant cell lines showed significant decreases in OPA1 mRNA and protein expression, mitochondrial membrane potential, and ATP synthesis. A marked deficiency of the long isoform of OPA1 was observed in cells with OPA1 mutations in the middle domain and GTPase effector domain. Confocal microscopy revealed increased mitochondrial fragmentation in OPA1 mutant cells. OPA1 mutant cells also displayed reduced oxygen consumption and underwent glycolysis to produce ATP. Moreover, OPA1 mutations caused the accumulation of oxidative damage. CONCLUSIONS: Our experiments demonstrated that OPA1 mutations induced mitochondrial fragmentation, uncoupled mitochondrial respiration, and elicited dysfunctional bioenergetics. However, there were no significant differences among the various OPA1 mutations.

Neuroimaging and clinical features of patients with optic nerve hypoplasia in Taiwan.

PURPOSE: To investigate the clinical and neuroradiographic features of Chinese patients with optic nerve hypoplasia (ONH). METHODS: This was a retrospective case series study. The medical records and magnetic resonance imaging (MRI) studies of patients diagnosed with ONH from September 2001 to December 2013 in the neuro-ophthalmology clinic of Taipei Veterans General Hospital were reviewed. RESULTS: A total of eight eyes of five patients with ONH were enrolled in this study (1 male, 4 females). The mean age at diagnosis was 14.5 ± 12.0 years (range 0.25-30 years). Ocular examination revealed approximately half of the eyes had tortuous retinal vessels. In MRI studies, all patients had midline brain abnormalities including ectopic posterior pituitary gland (60%), agenesis of septum pellucidum (20%), and Rathke's cleft cyst (20%). Two patients had endocrinopathies-one suffered from hypopituitarism and the other had hyperprolactinemia. Both of them showed ocular findings of tortuous retinal vessels. CONCLUSION: A high prevalence of midline brain abnormalities was noted in ONH patients of Chinese ethnicity. The presence of tortuous retinal vessels in patients with a midline brain anomaly may indicate the occurrence of endocrinopathy.

Leber's hereditary optic neuropathy masquerading as optic neuritis with spontaneous visual recovery.

We report a case of Leber's hereditary optic neuropathy (LHON) masquerading as optic neuritis with late visual recovery. A 28-year-old man had gradual visual loss in both eyes for two weeks. Visual acuity was 0.4 in the right eye and 0.7 in the left. Fundus examination revealed hyperaemic discs in each eye. Fluorescein angiography revealed dye leakage at both optic discs in the late phase. Static perimetry (Humphrey 30-2) revealed bilateral relative central scotomata. Magnetic resonance imaging of the optic nerves was normal and his lumbar puncture showed normal opening pressure. He received steroid pulse therapy for three days. Nevertheless, vision in his right eye deteriorated to 0.1 one month later and left vision worsened to 0.05 six months later. Fifteen months after onset, his vision began to improve. At 21 months, his vision recovered to 0.9 R and 1.0 L. Peripheral blood DNA sequencing revealed 14484 mutation of mitochondrial DNA (mtDNA). Visual recovery can occur in patients with Leber's hereditary optic neuropathy with mtDNA 14484 mutation. LHON could be misdiagnosed as optic neuritis in some cases. Molecular examination of mtDNA mutation can confirm the diagnosis of LHON in clinically controversial patients. We should keep in mind the diagnosis of LHON when optic neuritis shows poor response to pulse therapy.

The effect of photo-oxidative stress and inflammatory cytokine on complement factor H expression in retinal pigment epithelial cells.

PURPOSE: Genetic variation in complement factor H (CFH) has been implicated as a major risk factor for age-related macular degeneration (AMD). The reduction in CFH amount or its complement-modulating activity may lead to inadequate control of complement-driven inflammation at the outer retina. We explored the effect of photo-oxidative stress and inflammatory cytokine on the expression of CFH in retinal pigment epithelial (RPE) cells. METHODS: Cultured human RPE cells were exposed to blue light in the presence of interferon-γ (IFN-γ). CFH expression in cell lysate was examined by Western blot and the secretory CFH in culture medium was analyzed by ELISA. RPE cells were treated with vitamin C and exogenous superoxide dismutase mimetic (Tempol) before photo-oxidative treatments. The intracellular reactive oxygen species were examined by flow cytometry. RESULTS: IFN-γ increased CFH expression in RPE and the expression was suppressed significantly under concomitant blue light illumination. The secretory CFH level also decreased significantly under blue light illumination, which was related to the decreased intracellular mRNA and protein expressions of CFH. The suppression was mediated through an oxidative mechanism, and was particularly related to superoxide anion generation. The suppression of CFH expression in RPE under blue light illumination was abrogated by vitamin C and Tempol. CONCLUSIONS: Photo-oxidative stress reduces the ability of IFN-γ to increase CFH expression in RPE. Apart from reducing the oxidative damage, vitamin C reduces the suppression of CFH under photo-oxidative stress. These results suggest a new perspective of the interaction between oxidative stress and inflammation, and provide a potential novel treatment strategy for age-related macular degeneration.

Idiopathic intracranial hypertension: clinical features in Chinese patients.

PURPOSE: To describe the clinical features and visual outcomes of idiopathic intracranial hypertension (IIH) in Chinese patients. METHODS: We retrospectively reviewed the charts of patients diagnosed with IIH in Taipei Veterans General Hospital from 1981 to 2009. Demographic data, clinical features, laboratory data, treatment, and visual outcomes were analyzed. RESULTS: Twelve patients were included, seven female and five male patients. The mean age at onset was 32 (range, 13-65) years. Obesity was found in four (33%) patients. The most common clinical symptom was headache (75%), followed by transient visual obscuration (42%) and tinnitus (17%). Snellen visual acuity was equal to or better than 20/30 in 23 eyes, and the only eye with vision worse than 20/50 vision belonged to a patient who had been amblyopic since childhood. Visual field defects were detected in seven eyes by either Goldmann or automated perimetry. Generalized depression and an enlarged blind spot were the most common patterns. Ten patients were found to have bilateral disc edema. One patient with unilateral papilledema and one patient without papilledema were identified in the study. CONCLUSIONS: In IIH in Chinese, men are more likely to be affected than women, but obesity is not as frequent as reported in Western countries. Visual function outcomes are more favorable in Chinese patients.

"Seeing but not identifying": pure alexia coincident with prosopagnosia in occipital arteriovenous malformation.

BACKGROUND: Pure alexia and prosopagnosia are two separate and uncommon disorders of visual recognition in neuro-ophthalmology. We report an extremely rare case of pure alexia coincident with prosopagnosia secondary to occipital arteriovenous malformation. The manifestations of these two visual recognition disorders are also described. METHODS: A 35-year-old, left-handed women had suffered from severe blurred vision when recognizing her family's faces and was unable to read or associate separate parts of a word into a whole word. Her visual field revealed slight right homonymous hemianopia. Computed tomography scans and magnetic resonance images were arranged and vertebral angiography confirmed the diagnosis of left occipital arteriovenous malformation. RESULTS: Gamma-knife stereoscopic radiotherapy was performed. Two months after the treatment, the ability to recognize faces and read improved and the visual field recovered. CONCLUSIONS: Ophthalmologists should keep in mind that usual complaints of "blurred vision" might correlate with unusual visual recognition disorders. Pure alexia and prosopagnosia have not been reported to occur together and the left-handed- dominance in our case leads to this scarce concurrence.

Novel mutations of the OPA1 gene in Chinese dominant optic atrophy.

PURPOSE: To investigate OPA1 gene mutations in Chinese patients with autosomal dominant optic atrophy and sporadic optic atrophy. DESIGN: Molecular genetic studies and observational case series. PARTICIPANTS: Twenty-four patients from 10 unrelated Chinese pedigrees of autosomal-dominant optic atrophy, 35 isolated cases with bilateral optic atrophy of unknown cause, and 50 unrelated normal controls. METHODS: Genomic DNA was extracted from peripheral blood leukocytes. All 28 coding exons of the OPA1 gene and flanking intron splice sites were sequenced. Putative mutations were reexamined for segregation in the respective families by direct sequencing. Further characterization of selected splicing site mutations was performed by reverse transcription-polymerase chain reaction (PCR) of each patient's leukocyte mRNA. MAIN OUTCOME MEASURES: Direct sequencing of the OPA1 gene. RESULTS: Four OPA1 gene mutations were detected, including 2 splicing site mutations (c.1065+2T>C on intron 10 and c.1212+2insT on intron 12), 1 deletion (c.1776_1778delACT on exon 19), and 1 missense mutation (c.2846 T>C on exon 28). The c.1212+2insT, c.1776_1778delACT, and c.2846T>C mutations were newly identified OPA1 mutations. Reverse transcription (RT)-PCR and direct sequencing revealed that the splicing site mutations on c.1065+2T>C and c.1212+2insT caused skipping of exons 10 and 12, respectively. The c.1776_1778delACT mutation led to a deletion of the Leu amino acid on residue 593. OPA1 mutations were found in 4 of 10 familial cases (40 %) and in 1 of 35 sporadic cases of optic atrophy. CONCLUSIONS: OPA1 gene mutations are causative in Chinese autosomal-dominant optic atrophy and sporadic optic atrophy. Screening for OPA1 gene mutations in patients with childhood onset optic atrophy who have no affected relatives is useful in making the diagnosis.

Systemic lupus erythematosus-associated optic neuritis: clinical experience and literature review.

PURPOSE: This study aimed to evaluate the visual outcome of optic neuritis in patients with systemic lupus erythematosus (SLE). METHODS: A retrospective, case-observational study was conducted by reviewing eight patients with SLE-associated optic neuritis from January 1986 to October 2004. The demographic data, clinical manifestations, laboratory data, medical management and disease courses of these eight patients were retrospectively analysed. Main outcome measurements included final visual acuity (VA) and relapse of optic neuritis. Statistical analyses were made using the chi-square test and a linear regression model. The English-language literature on SLE-associated optic neuritis was reviewed. RESULTS: Initial visual loss was severe in SLE-associated optic neuritis. Seven patients (87%) had VA < 20/200 at onset. All patients received steroid pulse therapy followed by oral steroid tapering. Final visual outcome was highly variable, ranging from the complete recovery of VA in four patients, to partial recovery in one and poor recovery in three. Better visual recovery occurred in patients who received earlier treatment (within 10 days). However, longer duration of steroid administration was found to have no significant benefit on visual outcome. CONCLUSIONS: Systemic lupus erythematosus-associated optic neuritis is not common. However, it is important that ophthalmologists differentiate SLE-associated optic neuritis from idiopathic optic neuritis because of the severe visual impairment and steroid dependence associated with the former. Early diagnosis and prompt treatment are important for restoring visual function in these patients.

Reflux of jugular and retrobulbar venous flow in transient monocular blindness.

OBJECTIVE: Transient monocular blindness (TMB) attacks may occur during straining activities that impede cerebral venous return. Disturbance of cerebral and orbital venous circulation may be involved in TMB. METHODS: Duplex ultrasonography and Doppler-flow measurement of jugular and retrobulbar veins were performed in 134 consecutive patients with TMB and 134 age- and sex-matched control subjects. All recruited patients received thorough examinations to screen for possible underlying causes. RESULTS: Of the 134 patients with TMB, 48 patients had ipsilateral carotid arterial lesion and 7 patients had TMB attack(s) caused by cardiac embolism. Of the remaining 79 patients with undetermined cause, 46 had 3 or more TMB attacks (undetermined-frequent group) and 33 had fewer than 3 attacks. In comparison with the control subjects, the TMB patients had greater frequencies of jugular venous reflux (57 vs 30%; p < 0.0001; odds ratio [OR]: 3.079, 95% confidence intervals [CI]: 1.861-5.096) and flow reversal in the superior ophthalmic vein (RSOV; 37 vs 9%; p < 0.0001; OR: 6.052, CI: 3.040-12.048). The undetermined-frequent group had the greatest frequencies of jugular venous reflux (74%, 34 patients; OR: 6.66, CI: 3.13-14.17) and RSOV (59%, 27 patients; OR: 6.51, CI: 3.12-13.58). Of the 50 patients with RSOV, 47 (94%) had RSOV on the side of the TMB attacks. INTERPRETATION: The increased incidences of jugular and orbital venous reflux in TMB patients suggest that disturbance of cerebral and orbital venous circulation is involved in the pathogenesis of TMB, especially among patients with frequent attacks of undetermined cause.

Altered retrobulbar hemodynamics in patients who have transient monocular blindness without carotid stenosis.

BACKGROUND AND PURPOSE: This study was to evaluate the retrobulbar hemodynamics in patients who have transient monocular blindness (TMB) without carotid stenosis. METHODS: Fifty-nine patients who have TMB without carotid stenosis were studied along with 59 age- and sex-matched controls. Color Doppler-imaging was used to study the retrobulbar hemodynamic by measuring the flow velocities (peak-systolic velocity, and end-diastolic velocity), vascular resistance indices (pulsatility index, and resistance index) in central retinal arteries, short posterior ciliary arteries, and ophthalmic arteries. The patients were divided into 2 groups according to the attack frequency: group 1 (occasional TMB, 2 or fewer attacks, 26 patients) and group 2 (frequent TMB, 3 or more attacks, 33 patients). RESULTS: The risk factors for atherosclerosis were similar between the cases and controls. The means of end-diastolic velocity were significantly lower in central retinal arteries and ophthalmic arteries, and the pulsatility index and resistance index were significantly higher in all the 3 retrobulbar vessels in TMB patients than for the controls. The differences between patients and controls were greater for the group-2 patients. CONCLUSIONS: Patients who have TMB without carotid stenosis had altered retrobulbar hemodynamics with a generalized increase in vascular resistance in the retrobulbar arteries. The role of venous hypertension as an etiology needs further study.

Early relapse in multiple sclerosis-associated optic neuritis following the use of interferon beta-1a in Chinese patients.

PURPOSE: The incidence of multiple sclerosis (MS) is relatively rare in Chinese. The beneficial effect of interferon beta-1a in modifying the disease course of MS has been rarely analyzed in Chinese patients. The aim of this study was to investigate the clinical response to interferon beta1-a in Chinese patients with MS-associated optic neuritis (ON). METHODS: A retrospective case control study was conducted in 20 MS patients with optic nerve involvement. The interferon (IF) group comprised ten patients receiving interferon beta-1a. The noninterferon (NIF) group comprised another ten MS patients with optic nerve involvement who did not receive interferon treatment. The clinical characteristics, laboratory data, management, and disease course were retrospectively analyzed. The main outcomes of the study were the annualized relapse rate (ARR) for MS, and final visual outcome data. RESULTS: The ARR did not differ between the pretreatment period and the posttreatment period within the IF group. There was also no significant decrease of ARR in the IF group when compared with the NIF group. However, we observed an early recurrence of ON in 50% of the IF cases following the use of interferon beta-1a. The final visual outcome did not differ between the IF group and the NIF group. CONCLUSIONS: The use of interferon beta-1a should be carefully monitored because early relapse of ON may complicate the treatment course in this patient group.

Association of the Y402H polymorphism in complement factor H gene and neovascular age-related macular degeneration in Chinese patients.

PURPOSE: Age-related macular degeneration (AMD), with its complex traits and multiple risk factors, is the leading cause of blindness in the elderly. A strong association between a coding variant, Y402H, in the complement factor H gene (CFH) and AMD has been recently identified in white patients. This study was conducted to investigate the association between the Y402H polymorphism in CFH and neovascular AMD in Chinese patients. METHODS: One hundred sixty-three Chinese patients with neovascular AMD and 232 age-matched healthy controls were enrolled in the study. Genomic DNA from white blood cells was extracted. The Y402H polymorphism in CFH, with the substitution of T to C at nucleotide position 1277 in exon 9, was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. The association between the genetic polymorphism and the disease was examined by chi(2) test and logistic regression. RESULTS: The frequency of the risk allele, 1277C, was 11.3% in AMD patients compared with 2.8% in controls (P < 0.00001). Genotype frequency differed significantly between the two groups (1277TT 81.0%, 1277TC 15.3%, and 1277CC 3.7% in the AMD group; 1277TT 94.4%, 1277TC 5.6%, and 1277CC 0% in the control group; P < 0.0001). The 1277C allele significantly increased the risk for neovascular AMD and had an odds ratio of 4.4 (95% confidence interval [95% CI], 2.3-8.5; P < 0.00001). CONCLUSIONS: The allele frequency of Y402H polymorphism in CFH has an ethnic variation, with much lower 1277C frequency in Chinese than in white patients. Despite this, the polymorphism is significantly associated with neovascular AMD in the Chinese population.