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Anders Heijl

Publications and source records attributed to Anders Heijl.

At least 19 recordsLinked to original sources
PubMed2006

A placebo-controlled study of retinal blood flow changes by pentoxifylline and metabolites in humans.

AIM: To investigate the possible effects of pentoxifylline metabolites on retinal blood flow in humans. METHODS: A randomized, placebo-controlled, four-period cross-over study that was observer blinded and partly blinded for the eight participants. On one occasion a placebo was given as an intravenous (i.v.) infusion over 100 min. On the other three occasions pentoxifylline was administered as i.v. infusions over 100 min at a rate of 3 mg min(-1). Before two of the pentoxifylline infusions the subjects were pretreated with either ciprofloxacin or rifampicin. Retinal blood flow was measured by scanning laser doppler flowmetry (SLDF) in a selected area of the central temporal retina before, during and until 5 h after the end of infusion. Blood samples for concentration analyses of pentoxifyllin, R-M1, S-M1, M4 and M5 were taken serially and areas under the curves (AUCs) were calculated. Linear mixed models were used for the statistical analyses. RESULTS: Mean AUCs (ng h ml(-1)) were significantly increased for pentoxifylline (1964 vs. 1453) and S-M1 (5804 vs. 4227), but not R-M1 when pentoxifylline was co-administered with ciprofloxacin. The mean AUC for M5 was significantly reduced when subjects were pretreated with rifampicin (2041 vs. 3080). Pentoxifylline with and without pretreatment with rifampicin significantly increased retinal blood flow assessed as mean flow, pulsation (i.e. 1-systole/diastole), and diastolic flow (but not during systole), compared with placebo. The increases over placebo were more pronounced on diastolic flow, 9.7% (95% confidence interval 4.2, 15.5) than on mean flow, 4.6% (1.1, 8.3) after pentoxifylline administration. With pentoxifylline after rifampicin pretreatment the corresponding differences were 11.7% (5.8, 17.9) and 5.1% (1.4, 7.8) over placebo, respectively. After co-administration of pentoxifylline and ciprofloxacin we saw only a nonsignificant trend towards increased flow during diastole, but a significant decrease in pulsation. When AUCs for pentoxifylline and its metabolites were used as regressor variables to retinal mean flow we found that pentoxifylline, R-M1 and M5 had coefficients with a positive sign indicating that they enhanced the retinal blood flow. In contrast, S-M1 and M4 had coefficients with negative sign and thus appeared to decrease the blood flow in subjects treated with pentoxifylline. CONCLUSION: The R-M1 and M5 metabolites of pentoxifylline contributed significantly to the effects of pentoxifylline on retinal blood flow.

Adult↗
PubMed2005

Diurnal IOP fluctuation: not an independent risk factor for glaucomatous visual field loss in high-risk ocular hypertension.

PURPOSE: To establish whether intraocular pressure (IOP) fluctuations contribute to the risk of developing glaucoma in patients with high-risk ocular hypertension. METHODS: Ninety patients included in the Malmö Ocular Hypertension Study were examined every 3 months with office-hours diurnal tension curves and computerised perimetry. Patients were followed up prospectively for 10 years or until glaucomatous visual field loss could be demonstrated. Poststudy data were included in the analyses, extending maximum follow-up to 17 years. RESULTS: After 17 years, 37 patients had developed glaucomatous visual field defects. When applying univariate Cox regression analyses, mean IOP of all measurements during the prospective part of the study was a significant risk factor for developing glaucoma (95% confidence interval [CI] 1.08-1.39), while IOP fluctuations were almost significant (95% CI 0.98-1.93). When separating effects of mean IOP level and mean IOP fluctuation using Cox multiple regression analysis, only IOP level came out as significant (95% CI 1.09-1.38), and IOP fluctuations did not contribute to the risk (95% CI 0.80-1.60). IOP fluctuation depended linearly on IOP level (p<0.0001), i.e. IOP fluctuation was larger in eyes with higher IOP levels. CONCLUSION: IOP fluctuations were not an independent risk factor for the incidence of glaucomatous visual field loss in subjects with ocular hypertension.

Aged↗
PubMed2005

Risk of glaucoma in ocular hypertension with and without pseudoexfoliation.

PURPOSE: To compare glaucoma conversion rates in patients with ocular hypertension (OH) with and without pseudoexfoliation. DESIGN: Cohort study, based on 32,918 screening participants. PARTICIPANTS AND CONTROLS: Ninety-eight patients with OH and pseudoexfoliation and 98 matched controls. MAIN OUTCOME MEASURE: Perimetric glaucoma conversion. METHODS: A population-based glaucoma screening of elderly citizens of Malmö, Sweden, was conducted between 1992 and 1997 to recruit participants for the Early Manifest Glaucoma Trial. Screening participants with intraocular pressure (IOP) between 24 and 32 mmHg and pseudoexfoliation were compared to controls among other screening participants without pseudoexfoliation but matched for baseline IOP, age, and gender, and the 2 groups were invited to a reexamination. Computerized visual field tests were performed to identify persons with manifest glaucoma. Visual acuity, refraction, IOP, and central corneal thickness were also measured. RESULTS: After a mean of 8.7 years (range: 6.3-11.4), 54 of 98 patients (55.1%) with pseudoexfoliation at the baseline examination and 27 of 98 patients (27.6%) without pseudoexfoliation had developed glaucoma. The risk ratio was 2.0 (P<0.0001). CONCLUSION: The glaucoma conversion rate was twice as high in patients with OH and pseudoexfoliation as in control patients matched for IOP, age, and gender. Thus, pseudoexfoliation was a strong independent risk factor for glaucoma in patients with OH.

Aged↗
PubMed2005

Treatment and vision-related quality of life in the early manifest glaucoma trial.

PURPOSE: To evaluate the effect of treatment, visual function, and other factors on vision-targeted health-related quality of life (HRQOL) of patients with early glaucoma. DESIGN: Randomized clinical trial. PARTICIPANTS: Two hundred fifty-five patients with newly detected open-angle glaucoma and repeatable early visual field (VF) defects, 50 to 80 years old (66% female). METHODS: Patients were randomized to receive either betaxolol plus laser trabeculoplasty in eligible eye(s) or no initial treatment and had ophthalmologic examinations every 3 months. A Swedish translation of the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was self-administered at 2 follow-up visits (3 and 6 years after randomization). MAIN OUTCOME: Multiple linear regression analyses determined the effect of treatment and other factors on (1) VFQ-25 composite scores at the first administration and (2) change in scores between administrations. RESULTS: Two hundred thirty-three patients had 1 NEI VFQ-25 administration and 167 patients had 2 administrations. Internal consistency reliability was high for the composite VFQ-25 score (Cronbach alpha = 0.88) and satisfactory (alpha> or =0.76) for most subscale scores. At the first administration, the composite score was high (88.8+/-11.7). Mean subscale scores were also generally high (98.0-58.3) and were similar for each study group when analyzed separately. Most lower subscale scores were modestly but significantly related to worse visual acuity (VA) or mean deviation (MD) (better eye, r = 0.15-0.35). Composite scores were similar for treated and untreated patients. Lower composite scores were associated with low VA in the better eye (worse than 0.70) and worse perimetric MD (<4.16 decibels) and nuclear lens opacities (Lens Opacities Classification System II grade > or = 2), but not with age, gender, VF progression, intraocular pressure, cardiovascular disease, or hypertension. Between VFQ-25 administrations, larger decreases in the composite score were associated with larger decreases in VA (P<0.05), female gender (P = 0.001), and older age at first administration (P = 0.006). Treatment (assigned at randomization or later in the study) was not associated with change in HRQOL. CONCLUSIONS: Results suggest that absence or delay of treatment did not influence vision-targeted HRQOL in these newly diagnosed glaucoma patients. However, visual function affected vision-targeted quality of life up to 6 years after Early Manifest Glaucoma Trial enrollment.

Aged↗
PubMed2005

A long-term prospective study of risk factors for glaucomatous visual field loss in patients with ocular hypertension.

PURPOSE: To evaluate the importance of baseline risk factors for development of glaucomatous visual field loss in patients with high-risk ocular hypertension. METHODS: In the Malmö Ocular Hypertension Study, 90 patients were randomized to topical timolol or placebo treatment and observed prospectively for up to 10 years. Patients with elevated intraocular pressure (IOP) and with open angles and normal visual fields, plus at least one extra risk factor, were eligible. Risk factors were suspect disc or known disc hemorrhage, positive family history of glaucoma, pseudoexfoliation or pigment dispersion syndrome, diabetes, and mean IOP on DTC > or = 27 mm Hg. These risk factors and also the mean baseline IOP and IOP fluctuation, sex, age, and blood pressure were evaluated as predictors for development of reproducible glaucomatous visual field loss. In addition to the prospective data, post-study data were retrieved from patients' records extending maximum follow-up to 17 years. RESULTS: Thirty-seven patients developed glaucomatous visual field loss. Of all factors included in the analysis, disc appearance, older age, and higher IOP came out as significant risks. Suspect disc appearance increased the risk approximately three times, with a hazard ratio of 2.90, and CI: 1.34-6.30, the hazard ratio was 1.05 and CI: 1.03-1.09 per year of age, while mean baseline IOP increased the risk with 14% per mm Hg (CI: 1.01-1.28). CONCLUSION: Patients with ocular hypertension were at higher risk for developing glaucomatous visual field loss if discs were suspect, if IOP was high, and if the patient was older in age.

Adult↗
PubMed2005

Nordic research in ophthalmology.

Nordic ophthalmologists and vision scientists are active in many fields of eye research. This is most evident at the biannual Nordic Congress of Ophthalmology, most recently held in Malmö in June 2004. The authors here review some of the research in vision and ophthalmology presented at this meeting or published recently by Nordic scientists. This paper does not represent a comprehensive review of all Nordic research in the field, but attempts to give an overview of some of the activities underway in eye research in this part of the world.

Animals↗
PubMed2005

Effects of input data on the performance of a neural network in distinguishing normal and glaucomatous visual fields.

PURPOSE: To compare the performance of neural networks for perimetric glaucoma diagnosis when using different types of data inputs: numerical threshold sensitivities, Statpac Total Deviation and Pattern Deviation, and probability scores based on Total and Pattern Deviation probability maps (Carl Zeiss Meditec, Inc., Dublin, CA). METHODS: The results of SITA Standard visual field tests in 213 healthy subjects, 127 patients with glaucoma, 68 patients with concomitant glaucoma and cataract, and 41 patients with cataract only were included. The five different types of input data were entered into five identically designed artificial neural networks. Network thresholds were adjusted for each network. Receiver operating characteristic (ROC) curves were constructed to display the combinations of sensitivity and specificity. RESULTS: Input data in the form of Pattern Deviation probability scores gave the best results, with an area of 0.988 under the ROC curve, and were significantly better (P < 0.001) than threshold sensitivities and numerical Total Deviations and Total Deviation probability scores. The second best result was obtained with numerical Pattern Deviations with an area of 0.980. CONCLUSIONS: The choice of type of data input had important effects on the performance of the neural networks in glaucoma diagnosis. Refined input data, based on Pattern Deviations, resulted in higher sensitivity and specificity than did raw threshold values. Neural networks may have high potential in the production of useful clinical tools for the classification of visual field tests.

Adult↗
PubMed2004

Glaucoma and mortality.

PURPOSE: To compare mortality rates in glaucoma patients and matched controls from a large population screening as well as glaucoma patients diagnosed through routine clinical examination (self-selected patients). METHODS: A population-based screening of 32,918 elderly citizens of Malmö was conducted between 1992 and 1997. Individuals with newly detected, previously untreated open-angle glaucoma were identified. Two controls of the same age and gender were chosen among the screening negative participants for each patient. From the same birth cohorts, glaucoma patients seen in routine clinical practice (self-selected patients) were identified through retrospective examination of patient records from the Eye Department at Malmö University Hospital. The number and time of deaths for each group were determined based on centrally administered registers. RESULTS: Mean follow-up time was 7.75 years. Five-year mortality did not differ significantly between the groups, and was 9.2% among glaucoma patients from the screening (n=402), and 11.9% among the controls (n=804; p=0.7406). Self-selected glaucoma patients had a 5-year mortality of 8.5% (n=354), not significantly different from the screening-detected glaucoma patients (p=0.1361). Among glaucoma patients, neither IOP (p=0.1781) nor pseudoexfoliation (p=0.8882) was related to significantly increased mortality. CONCLUSIONS: The results of this study strongly suggest that the life expectancy of glaucoma patients does not differ from the population at large.

Aged↗
PubMed2004

Factors for progression and glaucoma treatment: the Early Manifest Glaucoma Trial.

PURPOSE OF REVIEW: This review summarizes factors for progression in the Early Manifest Glaucoma Trial (EMGT), including the effect of treatment. EMGT randomized patients with early glaucoma either to argon laser trabeculoplasty plus betaxolol (n = 129) or to no immediate treatment (n = 126) and followed them every 3 months. RECENT FINDINGS: Treated patients had delayed progression, as compared with controls. In Cox regression, EMGT treatment halved the risk of progression (hazard ratio = 0.50; 95% confidence interval: 0.35, 0.71). Risk decreased about 10% with each millimeter mercury of intraocular pressure (IOP) reduction from baseline; the higher (or lower) the IOP at follow-up, the higher (or lower) the risk. Baseline factors increasing progression were higher IOP, exfoliation, bilateral disease, worse perimetric mean deviation and older age; frequent disc hemorrhages at follow-up also increased risk. SUMMARY: EMGT treatment reduced progression risk in half, demonstrating the value of IOP lowering in early glaucoma. Age and indicators of disease severity also predicted progression.

Antihypertensive Agents↗
PubMed2004

The nerve fibre layer symmetry test: computerized evaluation of human retinal nerve fibre layer thickness as measured by optical coherence tomography.

PURPOSE: To present and test a new interpretative concept, the nerve fibre layer symmetry test (NST), for computerized evaluation of retinal nerve fibre layer thickness (RNFLT) as measured by optical coherence tomography (OCT) in glaucoma. METHODS: The NST concept was constructed and tested in a pilot study. A total of 32 healthy and 40 age-matched glaucomatous eyes were included and examined by OCT, computerized perimetry, RNFL/disc photography, tonometry and a general ophthalmologic examination. RESULTS: The observed NST sensitivity and specificity were high, at 38/40 eyes (95%) and 32/32 eyes (100%), respectively, and 40/40 eyes (100%), and 31/32 eyes (97%), respectively, when correcting the OCT RNFLT measurement for the influence of variability in image signal/quality. The NST sensitivity was 8-10% higher than the single most sensitive traditional OCT RNFLT parameter; this difference was not statistically significant in this small sample. CONCLUSION: The NST showed high specificity and sensitivity for detection of RNFLT attenuation indicating early to severe glaucoma. Although promising, the NST needs to be further developed and validated in larger study samples and in patients with various stages of glaucomatous damage.

Aged↗
PubMed2004

Appearance of the pattern deviation map as a function of change in area of localized field loss.

PURPOSE: To determine the influence of the spatial extent and the depth of localized field loss on the computation of the General Height (GH) method for estimating the diffuse component of visual field loss and, therefore, on the subsequent appearance of the Pattern Deviation (PD) map. METHODS: Varying shapes and depths of localized glaucomatous field loss were modeled in each of 82 Humphrey Field Analyzer Program 30-2 fields (82 normal eyes) by superimposing, on the fields from the normal eyes, the PD defect depth (P < 0.05) of one visual field from each of 123 patients with glaucoma. The difference in GH between each of the 10,086 modeled fields and the GH in the corresponding measured normal field was derived and the relationship to possible differences in the location-by-location significance levels of each pair of PD maps determined. RESULTS: For the group mean overestimation in the GH of -0.79 dB, the 50th, 90th, and 95th percentiles of the modeled fields described 23.4%, 37.9%, and 42.6% locations, respectively, exhibiting an underestimation in PD statistical significance. As the size of the superimposed field loss increased, the overestimation of the GH increased, and the underestimation of PD statistical significance became more apparent. This error was independent of defect depth. CONCLUSIONS: The localized component of field loss in glaucoma produced an overestimation of diffuse loss and a consequent underestimation of the severity of focal loss by PD analysis. This effect increased as the spatial extent of the loss became more extensive and will lead to an underestimation of progressive localized field loss.

Adult↗
PubMed2003

Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial.

OBJECTIVE: To assess factors for progression in the Early Manifest Glaucoma Trial (EMGT), including the effect of EMGT treatment. SETTING/PARTICIPANTS: Two hundred fifty-five open-angle glaucoma patients randomized to argon laser trabeculoplasty plus topical betaxolol or no immediate treatment (129 treated; 126 controls) and followed up every 3 months. METHODS: Progression was determined by perimetric and photographic optic disc criteria. Patient-based risk of progression was evaluated using Cox proportional hazard regression models and was expressed as hazard ratios (HR) with 95% confidence intervals (95% CI). RESULTS: After 6 years, 53% of patients progressed. In multivariate analyses, progression risk was halved by treatment (HR = 0.50; 95% CI, 0.35-0.71). Predictive baseline factors were higher intraocular pressure (IOP) (ie, the higher the baseline IOP, the higher the risk), exfoliation, and having both eyes eligible (each of the latter 2 factors doubled the risk), as well as worse mean deviation and older age. Progression risk decreased by about 10% with each millimeter of mercury of IOP reduction from baseline to the first follow-up visit (HR = 0.90 per millimeter of mercury decrease; 95% CI, 0.86-0.94). The first IOP at that visit (3 months' follow-up) was also related to progression (HR = 1.11 per millimeter of mercury higher; 95% CI, 1.06-1.17), as was the mean IOP at follow-up (HR = 1.13 per millimeter of mercury higher; 95% CI, 1.07-1.19). The percent of patient follow-up visits with disc hemorrhages was also related to progression (HR = 1.02 per percent higher; 95% CI, 1.01-1.03). No other factors were identified. CONCLUSIONS: Patients treated in the EMGT had half of the progression risk of control patients. The magnitude of initial IOP reduction was a major factor influencing outcome. Progression was also increased with higher baseline IOP, exfoliation, bilateral disease, worse mean deviation, and older age, as well as frequent disc hemorrhages during follow-up. Each higher (or lower) millimeter of mercury of IOP on follow-up was associated with an approximate 10% increased (or decreased) risk of progression.

Adrenergic beta-Antagonists↗
PubMed2003

The effects of antiglaucoma and systemic medications on ocular blood flow.

Based on the body of evidence implicating ocular blood flow disturbances in the pathogenesis of glaucoma, there is great interest in the investigation of the effects of antiglaucoma drugs and systemic medications on the various ocular vascular beds. The primary aim of this article was to review the current data available on the effects of antiglaucoma drugs and systemic medications on ocular blood flow. We performed a literature search in November 2002, which consisted of a textword search in MEDLINE for the years 1968-2002. The results of this review suggest that there is a severe lack of well-designed long-term studies investigating the effects of antiglaucoma and systemic medications on ocular blood flow in glaucomatous patients. However, among the 136 articles dealing with the effect of antiglaucoma drugs on ocular blood flow, only 36 (26.5%) investigated the effects of medications on glaucoma patients. Among these 36 articles, only 3 (8.3%) were long-term studies, and only 16 (44.4%) were double-masked, randomized, prospective trials. Among the 33 articles describing the effects of systemic medications on ocular blood flow, only 11 (33.3%) investigated glaucoma patients, of which only one (9.1%) was a double-masked, randomized, prospective trial. Based on this preliminary data, we would intimate that few antiglaucoma medications have the potential to directly improve ocular blood flow. Unoprostone appears to have a reproducible antiendothelin-1 effect, betaxolol may exert a calcium-channel blocker action, apraclonidine consistently leads to anterior segment vasoconstriction, and carbonic anhydrase inhibitors seem to accelerate the retinal circulation. Longitudinal, prospective, randomized trials are needed to investigate the effects of vasoactive substances with no hypotensive effect on the progression of glaucoma.

Eye↗
PubMed2003

Measuring visual field progression in the Early Manifest Glaucoma Trial.

AIMS: The Early Manifest Glaucoma Trial (EMGT) (316 eligible eyes) has used a new set of criteria to define visual field progression in glaucoma. This paper provides estimates of the amount of visual field worsening required to reach the EMGT definition of definite perimetric progression. METHODS: In the 148 eyes that reached definite progression, we first determined changes between baseline and the time of definite EMGT progression, both for mean deviation (MD) and for number of highly (p < 0.5%) significantly depressed test points in pattern deviation probability maps. Second, we studied whether such changes depended on baseline MD, intraocular pressure (IOP), age and time to progression, all of which are factors that affect the rate of field progression. RESULTS: In eyes reaching progression, the mean change in MD from baseline was -1.93 dB (SE +/- 0.20) and the mean change in number of significant points was +4.85 (SE +/- 0.35). These changes did not show linear dependency on baseline MD, IOP or time to progression. CONCLUSIONS: The average amount of field deterioration needed to reach EMGT visual field progression has been measured and expressed in more conventional units (i.e. a loss of about - 2dB in MD and an increase in about five highly significant points). These estimates will facilitate the clinical interpretation of the results of EMGT.

Aged↗
PubMed2003

Electrophysiology and ocular blood flow in a family with dominant optic nerve atrophy and a mutation in the OPA1 gene.

OBJECTIVE: To characterize the clinical phenotype, with emphasis on electrophysiology and blood flow measurements, of a family with dominant optic nerve atrophy and an identified mutation in the OPA1 gene. METHODS: Seven family members were examined. Ophthalmological evaluation included testing of visual acuity, ophthalmolscopy, kinetic perimetry, color vision testing, full-field electroretinography (ERG), multifocal electroretinography (MERG), and multifocal visual evoked potential (MVEP). Retrobulbar arterial blood flow and retinal capillary perfusion was measured in three patients using scanning laser Doppler flowmetry (SLDF) and color Doppler imaging techniques. PCR-SSCP and DNA sequencing determined the presence of a mutation in exon 18 of the OPA1 gene. RESULTS: The clinical characteristics varied considerably in the family. The ERG and the MERG demonstrated normal retinal function, while the MVEP was abnormal in all examined patients. Retinal and optic nerve head capillary perfusion was significantly decreased in the three patients examined with SLDF. Retrobulbar blood flow velocities were significantly decreased in the central retinal and ophthalmic arteries. In all seven examined subjects, a microdeletion (1756-1767del(12 bp)) in the OPA1 gene was identified. CONCLUSION: Patients with a mutation in the OPA1 gene have a very variable phenotype. MVEP and blood flow measurements are two new objective methods for an easier detection of this specific genetic optic nerve atrophy.

Adolescent↗
PubMed2003

Nordic research in ophthalmology.

PURPOSE: To provide an overview of some of the current activities in eye research in the Nordic countries. METHODS: The presentations at the biannual Nordic Congress of Ophthalmology, held in Tampere, Finland in 2002, were reviewed and the contributions found most noteworthy are included in this article along with a limited discussion of each research field. However, space requirements prevented the inclusion of many interesting scientific contributions. RESULTS: Important contributions in various subfields of eye research and ophthalmology are reviewed. These include cornea, cataract, paediatric ophthalmology, glaucoma, diabetic eye disease, age-related macular degeneration, physiology and pharmacology and oncology. CONCLUSIONS: Eye research is very active in the Nordic countries and significant contributions are being made to ophthalmology in several fields on a world scale. We hope to continue to review Nordic contributions to eye research after each Nordic Congress of Ophthalmology and plan to make the reviews more systematic and comprehensive in the future.

Biomedical Research↗