Melanoma-associated retinopathy with anti-TRPM1 autoantibodies showing concomitant Off-bipolar cell dysfunction.

BACKGROUND: To report the clinical features of a patient with melanoma-associated retinopathy (MAR) with anti-transient receptor potential cation channel, subfamily M, member 1 (TRPM1) autoantibodies showing concomitant Off-bipolar cell dysfunction. METHODS: We evaluated a patient with a past history of scalp melanoma presented with sudden-onset shimmering photopsia in both eyes. MAR was confirmed with complete ophthalmic examinations, electronegative electroretinogram (ERG), and the presence of anti-TRPM1 autoantibodies by Western blot analysis. S-cone ERG and photopic On-Off ERG were studied in this patient as well. RESULTS: The patient's best-corrected visual acuity was 6/30 in the right eye and 6/8.6 in the left eye. Fundus and OCT findings were unremarkable. Visual field test showed severe constriction in both eyes. His full-field ERG was electronegative. S-cone ERG recorded preservation of L/M-cone-mediated response and undetectable S-cone-mediated response. Photopic On-Off ERG disclosed attenuated On- and Off-response. Western blot analysis confirmed immunoreactivity of the patient's serum to a 30 kDa TRPM1 recombinant protein. Whole-body positron emission tomography scan detected lymph node metastases in the neck. CONCLUSIONS: Anti-TRPM1 autoantibody-positive MAR varies greatly in its presentation and clinical course. We present a case of anti-TRPM1 autoantibody-positive MAR with atypical feature of Off-bipolar cell involvement. A complete electroretinographic study together with identification of the pathogenic antiretinal autoantibodies may help better understand and subclassify the disease in the future.

Astrocytic hamartoma in a patient heterozygous for RIM1 mutation associated-retinal dystrophy.

BACKGROUND: Autosomal-dominant cone-rod dystrophy 7 (CORD7) has been documented in association with RIM1 mutation (c.2459 G>A). We report a patient with retinal dystrophy who was heterozygous for RIM1 missense variant with a newly found point mutation (c.4036 G>T). Clinical findings of this genetic variant manifested differently from a typical CORD7. In addition, astrocytic hamartomas at bilateral optic discs are also a unique feature, which has not been described in CORD previously. MATERIALS AND METHODS: Medical records of this patient were retrospectively reviewed. Genetic testing with whole exon sequencing was performed. RESULTS: This 43-year-old female with history of decreased night vision since childhood came to our hospital complaining of blurred vision in both eyes for more than half a year. Her best-corrected visual acuity was 20/200 in both eyes. Dilated fundoscopic examination revealed symmetric diffuse atrophy of retinal pigment epithelium with peripheral pigmentary clumps. Also, optic disc astrocytic hamartomas were found bilaterally. Optical coherence tomography revealed extensive disruption of inner segment/outer segment junction in both eyes. Visual field test showed severe peripheral defect sparing central vision. Electroretinogram demonstrated both rod and cone cells abnormalities. Subsequent genetic testing reported heterozygosity for the RIM1 (c.4036 G>T) mutation. CONCLUSIONS: This is the first reported case of RIM1 mutation-associated retinal dystrophy with a newly found point mutation (c.4036 G>T), which presented differently from a typical CORD7 and more similarly to the phenotype of RP. Furthermore, our finding of bilateral optic disc astrocytic hamartomas has not been reported in association with CORD previously.

Long-Term Rehabilitation Utilization Pattern Among Stroke Patients Under the National Health Insurance Program.

OBJECTIVE: The aim of this study was to understand the frequency of patients receiving rehabilitation services at various periods after stroke and the possible medical barriers to receiving rehabilitation. DESIGN: A retrospective cohort study was conducted using a nationally representative sample in Taiwan. A total of 14,600 stroke patients between 2005 and 2011 were included. Utilization of physical therapy or occupational therapy at different periods after stroke onset was the outcome variable. Individual and geographic characteristics were investigated to determine their effect on patients' probability of receiving rehabilitation. RESULTS: More severe stroke or more comorbid diseases increased the odds of receiving physical therapy and occupational therapy; older age was associated with decreased odds. Notably, sex and stroke type influenced the odds of rehabilitation only in the early period. Copayment exemption lowered the odds of rehabilitation in the first 6 mos but increased the odds in later periods. Rural and suburban patients had significantly lower odds of receiving physical therapy and occupational therapy, as did patients living in areas with fewer rehabilitation therapists. CONCLUSIONS: Besides personal factors, geographic factors such as urban-rural gaps and number of therapists were significantly associated with the utilization of post-stroke rehabilitation care. Furthermore, the influence of certain factors, such as sex, stroke type, and copayment exemption type, changed over time.

Single nucleotide variants lead to dysregulation of the human mitochondrial NAD(P)+-dependent malic enzyme.

Human mitochondrial NAD(P)+-dependent malic enzyme (ME2) is well recognized to associate with cancer cell metabolism, and the single nucleotide variants (SNVs) of ME2 may play a role in enzyme regulation. Here we reported that the SNVs of ME2 occurring in the allosteric sites lead to inactivation or overactivation of ME2. Two ME2-SNVs, ME2_R67Q and ME2-R484W, that demonstrated inactivating or overactivating enzyme activities of ME2, respectively, have different impact toward the cells. The cells with overactivating SNV enzyme, ME2_R484W, grow more rapidly and are more resistant to cellular senescence than the cells with wild-type or inactivating SNV enzyme, ME2_R67Q. Crystal structures of these two ME2-SNVs reveal that ME2_R67Q was an inactivating "dead form," and ME2_R484W was an overactivating "closed form" of the enzyme. The resolved ME2-SNV structures provide a molecular basis to explain the abnormal kinetic properties of these SNV enzymes.

Recovery of visual field defects following vitrectomy for proliferative diabetic retinopathy: A case report.

RATIONALE: Proliferative diabetic retinopathy (PDR) may lead to severe visual impairment, and visual field (VF) loss in such patients has been reported. Vitrectomy is performed in PDR cases complicated with either vitreous hemorrhage or tractional retinal detachment to restore their visual acuity. However, its effect on VF defects is limited in data. Herein, we report the recovery of VF defects following vitrectomy in a patient with PDR. PATIENT CONCERNS: A 25-year-old female with bilateral PDR and vitreous hemorrhage received 2 monthly intravitreal injections of aflibercept in both eyes. Six months after her last injection, she presented with fibrovascular membrane formation in both eyes and VF defects of -9.02 dB and -20.05 dB in the right and left eye, respectively. DIAGNOSES: Proliferative diabetic retinopathy in both eyes. INTERVENTIONS: The patient underwent vitrectomy for her left eye. OUTCOMES: Although her visual acuity did not improve as expected, results from the Humphrey visual field analyzer showed notably improvement of her left eye (-9.05 dB) after the surgery. LESSONS: Vitrectomy potentially allows recovery of VF defects in patients with PDR.

Chronic rhinosinusitis after radiotherapy in patients with head and neck cancer: a population-based cohort study in Taiwan.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common post-radiotherapy (RT) side effect in patients with nasopharyngeal cancer (NPC). However, whether RT is a risk factor for CRS in patients with other types of head and neck cancer remains unclear. This study investigated the association, if any, between CRS and RT in patients with head and neck cancer. METHODS: This retrospective cohort study included the data of patients newly diagnosed as having head and neck cancer between January 1, 2005, and December 31, 2008, from the 2005 Longitudinal Health Insurance Database. Patients were categorized into the following groups according to the treatment regimens received: RT alone (RT-alone), RT combined with other treatments (any-RT), and treatments without RT (no-RT). The outcome was the occurrence of CRS after treatment. RESULTS: Of the 701 patients, 7% experienced CRS within 5 years after initial treatment. Patients were divided into subgroups according to different treatment policies, and the RT-alone group, any-RT group, and no-RT group had 5-year incidence of CRS of 12%, 9.3%, and 4.5%, respectively. Patients in the RT-alone and any-RT groups exhibited an increased risk of CRS compared with patients in the no-RT group (hazard ratio: 6.76 and 2.91; 95% confidence interval: 2.60 to 17.5 and 1.60 to 5.31, respectively). CONCLUSION: This is the first nationwide population-based cohort study to evaluate the risk of posttreatment CRS in patients with head and neck cancer. Our findings indicate that RT is a major risk factor for CRS. Thus, physicians should consider this potential risk in patients with head and neck cancer after RT.

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.

Different expression patterns of renal Na+/K+-ATPase α-isoform-like proteins between tilapia and milkfish following salinity challenges.

Euryhaline teleosts can survive in a broad range of salinity via alteration of the molecular mechanisms in certain osmoregulatory organs, including in the gill and kidney. Among these mechanisms, Na+/K+-ATPase (NKA) plays a crucial role in triggering ion-transporting systems. The switch of NKA isoforms in euryhaline fish gills substantially contributes to salinity adaptation. However, there is little information about switches in the kidneys of euryhaline teleosts. Therefore, the responses of the renal NKA α-isoform protein switch to salinity challenge in euryhaline tilapia (Oreochromis mossambicus) and milkfish (Chanos chanos) with different salinity preferences were examined and compared in this study. Immunohistochemical staining in tilapia kidneys revealed the localization of NKA in renal tubules rather than in the glomeruli, similar to our previous findings in milkfish kidneys. Protein abundance in the renal NKA pan α-subunit-like, α1-, and α3-isoform-like proteins in seawater-acclimated tilapia was significantly higher than in the freshwater group, whereas the α2-isoform-like protein exhibited the opposite pattern of expression. In the milkfish, higher protein abundance in the renal NKA pan α-subunit-like and α1-isoform-like proteins was found in freshwater-acclimated fish, whereas no difference was found in the protein abundance of α2- and α3-isoform-like proteins between groups. These findings suggested that switches for renal NKA α-isoforms, especially the α1-isoform, were involved in renal osmoregulatory mechanisms of euryhaline teleosts. Moreover, differences in regulatory responses of the renal NKA α-subunit to salinity acclimation between tilapia and milkfish revealed that divergent mechanisms for maintaining osmotic balance might be employed by euryhaline teleosts with different salinity preferences.

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.

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.

Efficacy of intravitreal injection of anti-vascular endothelial growth factor agents for stage 4 retinopathy of prematurity.

PURPOSE: To investigate the efficacy of intravitreal injection of anti-vascular endothelial growth factor agents for Stage 4 retinopathy of prematurity. METHODS: Retrospective case series study. The medical records of patients receiving intravitreal injection of anti-vascular endothelial growth factor agents for Stage 4 retinopathy of prematurity from January 2007 to May 2012 in Taipei Veterans General Hospital were reviewed. RESULTS: A total of 13 eyes of 7 patients (3 boys and 4 girls) with Stage 4 retinopathy of prematurity were included. The mean gestational age and birth weight were 27.6 ± 2.6 weeks (range, 24.5-30.5 weeks) and 893.1 ± 293.2 g (range, 550-1422 g), respectively. The mean age at the time of injection was 38.2 ± 1.9 weeks (range, 36.0-41.5 weeks) postmenstrual age, and the mean follow-up period was 37.8 ± 19.5 months (range, 11.0-67.5 months). The active neovascularization regressed rapidly, and the anatomical outcomes were favorable in all patients. One eye developed recurrent retinal hemorrhage with localized retinal detachment 21 weeks after initial treatment, which resolved after a second injection. There were no ocular or systemic complications in these patients. CONCLUSION: Intravitreal injection of anti-vascular endothelial growth factor agents may be effective as monotherapy or as supplement to failed laser treatment for patients with Stage 4 retinopathy of prematurity without additional surgical intervention. Further randomized controlled trials are necessary to compare the clinical efficacy and safety with other conventional interventions.

Hyperhomocysteinemia in patients with polypoidal choroidal vasculopathy: a case control study.

PURPOSE: To determine whether elevated plasma homocysteine and serum high sensitivity C-reactive protein (hsCRP) levels, two established risk factors of vascular diseases, are associated with polypoidal choroidal vasculopathy (PCV). DESIGN: Retrospective case-control study. METHODS: One hundred and nineteen consecutive patients with PCV and 119 matched controls were enrolled in a tertiary hospital from September 2008 to June 2013. Plasma homocysteine and serum hsCRP levels were measured. Associations among plasma homocysteine, serum hsCRP levels and PCV were further evaluated using multivariable logistic regression analysis. RESULTS: The median plasma homocysteine level was significantly higher in patients with PCV than in the controls (12.20 µmol/L vs. 9.80 µmol/L, p<0.001). The median serum hsCRP level was slightly higher in the PCV group (0.16 mg/dl vs. 0.11 mg/dl in control group, p = 0.07). After multivariable logistic regression analysis, each 1 µmol/L increase of plasma homocysteine was associated with a 1.5-fold increase in likelihood of having PCV (OR, 1.54; 95% confidence interval (CI), 1.33-1.79, p<0.001). CONCLUSIONS: Hyperhomocysteinemia was associated with PCV and might play a role in the pathogenesis of PCV.

Short-term external buckling with pneumatic retinopexy for retinal detachment with inferior retinal breaks.

PURPOSE: To introduce a new approach for short-term external scleral buckling with pneumatic retinopexy for the management of rhegmatogenous retinal detachment with inferior retinal breaks. DESIGN: Retrospective, noncomparative, interventional case series. METHODS: A review of 33 consecutive eyes of 31 patients who underwent external buckling with pneumatic retinopexy for uncomplicated rhegmatogenous retinal detachment with inferior retinal breaks from December 2006 through December 2010. An external buckle was made of a 505 sponge sutured along the blunt side of a 279 tyre (MIRA Inc). The buckle was inserted deeply into the inferior fornix without suture after pneumatic retinopexy and was kept in place for 3 days. Primary and final anatomic outcomes, visual acuity, and adverse events were recorded. RESULTS: All patients tolerated the procedure. The mean follow-up period was 24.0 months (range, 9 to 61 months). Primary success, defined as successful retinal reattachment within 6 months without further treatment, was achieved in 29 (87.9%) eyes. All patients attained final retinal reattachment (100%). Overall, the mean best-corrected visual acuity improved significantly at the end of follow-up (0.30 logarithm of the minimal angle of resolution units; Snellen equivalent, 6/12), compared with the preoperative best-corrected visual acuity (0.82 logarithm of the minimal angle of resolution units; Snellen equivalent, 6/38; P < .001). CONCLUSIONS: Short-term external buckling with pneumatic retinopexy is a novel and effective treatment for rhegmatogenous retinal detachment with inferior retinal breaks, with a comparable success rate with other treatment methods. This approach also can avoid complications of long-term buckle implantation. Further comparative cohort studies may be necessary to compare the clinical efficacy with other conventional operations.