Search

PurposeTo evaluate postoperative metamorphopsia in macula-off rhegmatogenous retinal detachment (RRD) and its association with visual function, vision related quality of life, and optical coherence tomography (OCT) findings.Methods45 patients with primary macula-off RRD were included. At 12 months postoperatively, data on metamorphopsia using sine amsler charts (SAC), best corrected visual acuity (BCVA), letter contrast sensitivity, color vision (saturated and desaturated color confusion indexes), critical print size, reading acuity, the 25-item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), and OCT, were obtained.ResultsMetamorphopsia was present in 39 patients (88.6%), with most of them (n = 35, 77.8%) showing only mild metamorphopsia (SAC score = 1). Patients with metamorphopsia had significantly worse postoperative BCVA (p = 0.02), critical print size (pConclusionThe prevalence of postoperative metamorphopsia in macula-off RRD patients is high, however, the degree of metamorphopsia is relatively low. When metamorphopsia is present, visual functions seem to be compromised, while vision related quality of life is only mildly affected.

PURPOSE. We estimated the relative importance of genes and environment in dry eye disease (DED) using a classic twin study.METHODS. A large sample of 3930 female monozygotic and dizygotic twins from the UK Adult Twin Registry (TwinsUK) was questioned about the presence of a DED diagnosis and about DED symptoms in the preceding 3 months. In addition, a subset of 606 twins was examined for several dry eye signs. Genetic and environmental effects were estimated using maximum likelihood structural equation modeling.RESULTS. All DED outcome variables showed higher correlation in monozygotic twin pairs than in dizygotic twin pairs, suggesting genes have a contributory role in DED. The DED symptoms showed a heritability of 29% (95% confidence interval [CI], 18%-40%). A clinician's diagnosis of DED with concurrent use of artificial tears showed a heritability of 41% (95% CI, 26%-56%). Estimates of the heritability of DED signs were 25% (95% CI, 7%-42%) for interblink interval, 58% (95% CI, 43%-70%) for Schirmer value, 40% (95% CI, 25%-53%) for tear osmolarity, and 78% (95% CI, 59%-90%) for the presence of blepharitis. The unique environment explained the remainder of the variance. We found no significant heritability for tear breakup time.CONCLUSIONS. Genetic factors contribute moderately to the diagnosis, symptoms, and the signs of DED. Compared to other ocular phenotypes, the lower heritability might reflect some of the difficulties in objective phenotyping of DED in a population-based sample. However, future genetic studies are now justified and may help in unraveling the pathophysiology of DED.

PURPOSE: To investigate clinical characteristics of dry eye disease (DED) patients with a chronic pain syndrome.DESIGN: Cross-sectional. study.METHODS: Four hundred twenty-five patients of a tertiary care DED patient cohort in the Netherlands were included. Chronic pain syndromes irritable bowel syndrome, chronic pelvic pain, and fibromyalgia were assessed by questionnaires. Outcome variables were the Ocular Surface Disease Index (OSDI) symptom questionnaire, tear osmolarity, Schirmer test, tear breakup time, conjunctival hyperemia, staining of the cornea and conjunctiva, and amount of mucus. Outcomes were cross-sectionally compared between DED patients with a chronic pain syndrome and those without.RESULTS: A total of 74 out of 425 DED patients (17%) had at least 1 chronic pain syndrome. The total symptom score was significantly higher in DED patients with a chronic pain syndrome than in those without (45.8 vs 33.8, P CONCLUSION: In DED patients, chronic pain syndromes are common and are associated with increased severity of DED symptoms across all domains of the OSDI, even though objective ocular surface signs are no worse. In clinical practice, more awareness of chronic pain syndromes might help in understanding the discrepancy between signs and symptoms in DED. (C) 2016 by Elsevier Inc. All rights reserved.

Pharmacogenetic studies have demonstrated significant associations between several candidate genes (DRD2, DRD3, 5HTR2A and 5HTR2C, COMT and MTHFR) and antipsychotic drug response. The present study investigates the effect of nine polymorphisms in these genes for an association with antipsychotic treatment response. 329 Caucasian patients with a non-affective psychotic disorder using antipsychotics were included. All patients participated in the longitudinal GROUP-study in The Netherlands. We genotyped 9 SNPs in 6 candidate genes (DRD2: Taql_A, -141C; DRD3: Ser9Gly; HTR2A: 102-T/C, His452Tyr; HTR2C: Cys23Ser; COMT: Val158Met; MTHFR: 677-C/T) using standard protocols. Polymorphisms were based on previous studies showing associations with positive symptoms treatment response. The Clinical Global Impression Improvement (CGI-I) scale was used to assess improvement in positive psychotic symptoms since the start of current antipsychotic treatment. Ordinal regression was used for association analyses. Ninety percent of the patients used second generation antipsychotics, with olanzapine (28%) and risperidone (29%) being the most prescribed drugs. Ser9Gly of the dopamine D3 receptor gene (P value 0.034) and 677-C/T of MTHFR (P value 0.019) were tested statistically significant. Gly-carriers and T-carriers, respectively, showed more clinical improvement on the CGI-I. The other polymorphisms did not show a statistically significant association (P values>0.10). In conclusion, we replicated two out of nine of the previously reported associations between polymorphisms and treatment response. The direction and magnitude of the associations presented here in DRD3 (Ser9Gly) and MTHFR (677-C/T) are in line with previous association studies in Caucasian patients. These polymorphisms may be of value for predicting clinical response. (C) 2012 Elsevier B.V. and ECNP. All rights reserved.

Background: In two previous studies we investigated the association between the rs1414334 C/G and 759 C/T polymorphisms in the HTR2C gene, coding for the 5HT2c-receptor, and prevalence of the metabolic syndrome in a schizophrenic population. In both studies we found an association between the variant rs1414334 C-allele and an increased prevalence of the metabolic syndrome. Objectives: The objective of the current study was to try to replicate our previous findings in a different patient sample. Methods: Patients were included from an ongoing ' Pharmacotherapy Monitoring and Outcome survey'. A crosssectional design was used to investigate the association between HTR2C variants and the metabolic syndrome in patients diagnosed with schizophrenia or related disorders. Patients ≥18 years, using antipsychotics, were eligible for inclusion. Primary endpoint was prevalence of the metabolic syndrome. Primary determinants were the 759 C/Tand rs1414334:C>G polymorphisms in the X-linked HTR2c gene. The association between carriership of the variant HTR2C alleles and prevalence of the metabolic syndrome was investigated with logistic regression. Data were investigated for potential confounding effects of age, ethnicity, diagnosis, sex, SSRI's and antipsychotics. Results: 186 patients, mainly male (68%) and Caucasian (93%) were included. Age, sex, antipsychotic drugs, use of SSRI's and DSM-IV diagnosis were confounders and included in the multi-variate analysis. The variant rs1414334 C-allele, but not the variant 759-T allele, was significantly associated with the metabolic syndrome (Adjusted OR 3.99; 95%CI 1.40-11.33). Conclusions: This study confirms our previous findings that the variant rs1414334 C-allele is associated with the metabolic syndrome.

Pharmacogenetic studies on antipsychotic-induced movement disorders (MD) in schizophrenia so far have focused mainly on tardive dyskinesia. Only a few examined the more acute antipsychotic-induced MD such as parkinsonism and akathisia. Notably, all MD relate to deregulation of the dopamine system.This study aimed to replicate previously reported associations in candidate genes for acute and tardive antipsychotic-induced MD in a young Caucasian sample.In 402 patients (median age 26 years), a total of 13 polymorphisms were genotyped in eight dopamine-related candidate genes selected a priori from the literature (regarding dopamine and serotonin receptors, dopamine degradation, and free radicals scavenging enzymes pathways).Patients with MD used on average a higher haloperidol dose equivalent when compared to those without MD. The prevalence of MD was high and did not differ between first- and second-generation antipsychotics. Significant associations were found between (a) the TaqI_D polymorphism and akathisia (OR = 2.3, p = 0.001 for each extra C-allele) and (b) the -141C polymorphism and tardive dyskinesia (OR = 0.20, p = 0.001 for each extra Del allele). The other polymorphisms were not significantly associated with an MD.Two associations were found between genetic variation TaqI_D and the -141C polymorphisms in the DRD2 gene and antipsychotic-induced MD; one with acute akathisia and one with tardive dyskinesia. These were previously reported to be associated with tardive dyskinesia and acute parkinsonism, respectively. These results suggest that the contribution of these DRD2 gene variants in the vulnerability of antipsychotic-induced MD takes place in a more general or pleiotropic way.

The article above indicates that DED was classified by asking about a clinician’s diagnosis of dry eye disease together with the concomitant use of artificial tear eye drops or gel. The classification that was used in the article was by asking about a clinician’s diagnosis of dry eye disease together with the presence of dry eye symptoms in the last three months. So, in the methods section 2.2 Measures the sentence ‘DED was classified by asking about a clinician’s diagnosis of dry eye disease together with the concomitant use of artificial tear eye drops or gel, as used in another population-based study [14].’ should be replaced by ‘DED was classified by asking about a clinician’s diagnosis of dry eye disease together with the concomitant presence of dry eye symptoms for the past three months, as used in other population-based studies [14,60].’ The authors regret this error. However, it does not affect the results or message of the article. [60] Moss SE, Klein R, Klein BE. Long-term incidence of dry eye in an older population. Optom Vis Sci 2008;85:668–74.

A. Risselada1 °, J. Vehof2, R. Bruggeman3, B. Wilffert4, D. Cohen5, A.F. Al Hadithy6, J. Arends7, H. Mulder8. 1Wilhelmina Hospital Assen, Department of Clinical Pharmacy, Assen, The Netherlands; 2University Medical Centre Groningen, Department of Epidemiology, Groningen, The Netherlands; 3University Medical Centre Groningen, Department of Psychiatry, Groningen, The Netherlands; 4University Medical Centre Groningen, Department of Pharmacotherapy and Pharmaceutical Care, Groningen, The Netherlands; 5Mental Health Services NHN, Department of Chronic Care, Heerhugowaard, The Netherlands; 6Erasmus University Medical Centre, Department of Hospital Pharmacy, Rotterdam, The Netherlands; 7Mental Health Services Drenthe, Department of psychosis, Assen, The Netherlands; 8Utrecht University, Department of Pharmacoepidemiology and pharmacotherapy, Utrecht, The Netherlands

IMPORTANCE Dry eye disease (DED) is common, but little is known about factors contributing to symptoms of dry eye, given the poor correlation between these symptoms and objective signs at the ocular surface.OBJECTIVE To explore whether pain sensitivity plays a role in patients' experience of DED symptoms.DESIGN, SETTING, AND PARTICIPANTS A population-based cross-sectional study of 1635 female twin volunteers, aged 20 to 83 years, from the TwinsUK adult registry.MAIN OUTCOMES AND MEASURES Dry eye disease was diagnosed if participants had at least 1 of the following: (1) a diagnosis of DED by a clinician, (2) the prescription of artificial tears, and/or (3) symptoms of dry eyes for at least 3 months. A subset of 689 women completed the Ocular Surface Disease Index (OSDI) questionnaire. Quantitative sensory testing using heat stimulus on the forearm was used to assess pain sensitivity (heat pain threshold [HPT]) and pain tolerance (heat pain suprathreshold [HPST]).RESULTS Of the 1622 participants included, 438 (27.0%) were categorized as having DED. Women with DED showed a significantly lower HPT (P=.03) and HPST (P=.003)-and hence had higher pain sensitivity-than those without DED. A strong significant association between the presence of pain symptoms on the OSDI and the HPT and HPST was found (P=.008 for the HPT and P=.003 for the HPST). In addition, participants with an HPT below the median had DED pain symptoms almost twice as often as those with an HPT above the median (31.2% vs 20.5%; odds ratio, 1.76; 95% CI, 1.15-2.71; P=.01).CONCLUSIONS AND RELEVANCE High pain sensitivity and low pain tolerance are associated with symptoms of DED, adding to previous associations of the severity of tear insufficiency, cell damage, and psychological factors. Management of DED symptoms is complex, and physicians need to consider the holistic picture, rather than simply treating ocular signs.

Background: In two previous studies we investigated the possible association between the rs1414334 C/G and 759 C/T polymorphisms in the gene that encodes the 5HT2c receptor (HTR2c) and prevalence of the metabolic syndrome in a schizophrenic population [1,2]. In both studies we found an association between the variant rs1414334 C-allele and an increased prevalence of the metabolic syndrome. The objective of the current study was to try to replicate our previous findings in a different patient sample. Methods: Patients were included from an ongoing 'Pharmacotherapy Monitoring and Outcome survey': PHAMOUS (http:// www.phamous.eu/). PHAMOUS combines a yearly somatic screening with routine outcome assessment in patients using antipsychotics. A cross-sectional design was used to investigate the association between HTR2C variants and the metabolic syndrome in patients diagnosed with schizophrenia or related disorders. Patients, ≥18 years, were eligible for inclusion if they used antipsychotic drugs and gave informed consent. Primary endpoint was prevalence of the metabolic syndrome, as defined by the definition by the National Cholesterol Education Program's Adult Treatment panel III (NCEP:ATP IIIa). HbA1c was used when fasting glucose values were unavailable. Secondary endpoints were associations between HTR2c polymorphisms and individual parameters contributing to the metabolic syndrome, as well as effects of individual antipsychotics. Primary determinants were the 759 C/T and rs1414334:C>G polymorphisms in the X-linked HTR2c gene. The association between HTR2C genotypes (carriership of the variant HTR2C allele) and prevalence of the metabolic syndrome was investigated with logistic regression. Results were expressed as Odds Ratio's with a 95% confidence interval (95% CI). Data were investigated for potential confounding effects of age, ethnicity, DSM-IV diagnosis, gender, use of SSRI's and antipsychotic drugs. Results: In total, 186 patients, mainly male (68%) and Caucasian (93%) were included. Olanzapine (23%), risperidone (22%) and clozapine (17%) where the most frequently prescribed antipsychotic drugs. The variant rs1414334 C-allele was significantly associated with the metabolic syndrome (OR 3.99; 95% CI 1.40-11.33) (table 1). There was a trend for an association between the variant rs1414334 C-allele and the metabolic syndrome in patients using risperidone (OR 16.50; 95% CI 0.73-375.43, p 0.08). There was also a trend for an association between the variant rs1414334 C-allele and an increased risk for reaching the cutoff points for lowered HDL (OR 2.47; 95% CI 0.95-6.42) and elevated triglyceride levels (OR 2.21; 95% CI 0. 94-5.18) respectively).(Table presented) Conclusions: This study confirms our previous findings that the variant C-allele of the rs1414334 polymorphism is associated with the metabolic syndrome.