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Purpose: iCare tonometers are easy-to-use and portable devices for measuring the intraocular pressure (IOP). Purpose was to evaluate the IOP values measured by both novel iCare ic100 and conventional model TA01i devices in unselected population. Methods: IOP was measured with iCare ic100 and TA01i tonometers in 149 participants aged 32–33 years (born in 1985 or 1986) of the Northern Finland Birth Cohort Eye 2 study. The right eye of each participant was selected for analysis. We also collected data on axial length, corneal curvature and central corneal thickness (CCT). Bland-Altman plot was used for comparing the values obtained by these devices. Results: Mean IOP measured with the ic100 device was 13.8 (3.4) mmHg, with TA01i it was 12.5 (3.0) mmHg. The mean difference between these devices was 1.30 mmHg ( p 2 was 0.694. In Bland-Altman analysis, the agreement between the two tonometers ic100 and TA01i was constantly good (mean difference −1.30, ic100 device showing higher measures). There was a correlation between IOP and CCT ( r = 0.269, p Conclusion: In summary, we found ic100 rebound tonometry to be both reliable and effective, although CCT may influence IOP measurements with ic100 and TA01i. Therefore, iCare ic100 is suitable for IOP measurement in large cohort studies.

Purpose The aim of this study was to compare the measurements of intraocular pressure by two tonometers, the Icare rebound tonometer and the Goldmann applanation tonometer, in a randomised screening study. The influence of refraction and central corneal thickness on the measurements was also evaluated. Methods Intraocular pressure was measured with rebound tonometer and Goldmann applanation tonometer in 1266 participants; refraction and central corneal thickness were also determined. One randomised eye of each participant was selected for this report’s analysis. A Bland–Altman plot was used to compare the values obtained with the two devices. Results The correlation between rebound tonometer and Goldmann applanation tonometer was good: the intraclass correlation coefficient (r) between the two methods was 0.735 ( p Conclusion Measurements with rebound tonometer and Goldmann applanation tonometer are relatively uniform although rebound tonometer slightly overestimated intraocular pressure. Both rebound tonometer and Goldmann applanation tonometer and the difference between these devices were affected by central corneal thickness but not by refraction. Higher astigmatism affected Goldmann applanation tonometer more than rebound tonometer. It is concluded that rebound tonometer is a reliable method for measuring intraocular pressure in a population-based screening study.

This paper describes a holistic, yet simple and comprehensible, ecosystem model to deal with multiple and complex challenges in eyecare. It aims at producing the best possible wellbeing and eyesight with the available resources. When targeting to improve the real-world cost-effectiveness, what gets done in everyday practice needs be measured routinely, efficiently and unselectively. Collection of all real-world data of all patients will enable evaluation and comparison of eyecare systems and departments between themselves nationally and internationally. The concept advocates a strategy to optimize real-life effectiveness, sustainability and outcomes of the service delivery in ophthalmology. The model consists of three components: (1) resource-governing principles (i.e., to deal with increasing demand and limited resources), (2) real-world monitoring (i.e., to collect structured real-world data utilizing automation and visualization of clinical parameters, health-related quality of life and costs), and (3) digital innovation strategy (i.e., to evaluate and benchmark real-world outcomes and cost-effectiveness). The core value and strength of the model lies in the consensus and collaboration of all Finnish university eye clinics to collect and evaluate the uniformly structured real-world outcomes data. In addition to ophthalmology, the approach is adaptable to any medical discipline to efficiently generate real-world insights and resilience in health systems.

Purpose: The optic nerve head (ONH) is a part of the brain that can be evaluated through the transparent medium of the eye. The purpose of this study was to explore the possible correlations among the properties of the optic nerve head, maternal factors during pregnancy and neonatal parameters in a randomized sample of a birth cohort. Methods: The Northern Finland 1966 Birth Cohort has been prospectively monitored since their antenatal period. Data on pregnancy and neonatal period were collected during gestation and right after birth in 1966. A randomized sample of 3070 subjects underwent an ophthalmic assessment at the age of 46–48 years. The examination protocol included scanning laser ophthalmoscopy with the Heidelberg Retina Tomograph. The ophthalmological parameters assessed were the disc area and the neuroretinal rim volume of the ONH. Results: We found that chronic pulmonary disease of the mother (p = 0.007), the number of gestational weeks (p = 0.030) and the mother’s highest measured systolic blood pressure (p = 0.035) during pregnancy had a statistically significant effect on the disc area. Smaller disc size was associated with pulmonary disease and early gestation. There was a significant difference in rim volume between genders (p

Purpose: The purpose of the study was to assess and compare the optic nerve head (ONH) and retinal nerve fibre layer (RNFL) parameters and image quality parameters obtained by Cirrus HD-OCT, GDxECC and HRT3 in a population-based screening study. Methods: This analysis examined 2566 subjects taking part in the Northern Finland Birth Cohort Eye study. Images with spectral domain OCT (Cirrus HD-OCT 4000), scanning laser ophthalmoscopy (HRT3) and scanning laser polarimetry (GDxECC) were obtained from each subject. The correlation of average and regional parameters of RNFL and ONH between devices was evaluated. Results: The RNFL thickness was 90.9 µm when measured with OCT, 24.6 µm with HRT and 48.1 µm with GDx. There was a high correlation between the disc and cup measurements with the HRT and OCT and the RNFL thickness of the OCT and GDx (r > 0.5). A statistically significant correlation was found between RNFL measurements of the HRT and OCT in the superior, temporal and inferior quadrants. Optical coherence tomography (OCT) signal strength correlated with the image quality parameters of the HRT and GDx. The percentage of good quality images was the lowest with the GDx. Conclusions: The RNFL thickness in Northern Finland birth cohort was at a lower level compared to other studies. The study confirms the difference in measuring ONH parameters between the imaging devices. However, significant correlations between devices were found in the cup volume and cup disc area ratio parameters of the OCT and HRT. The correlations between image quality parameters and glaucoma detection parameters were relatively low.

Purpose: The optic nerve head (ONH) is a part of the brain that can be easily studied through the transparent medium of the eye. We explored the relationship between the properties of the optic nerve head, the retinal nerve fiber layer (RNFL) and cognitive function. Methods: Participants of the Northern Finland Birth Cohort (NFBC) 1966 underwent an ophthalmic and cognitive assessment after randomization at age 46. The ophthalmological parameters obtained were the disc area and the neuroretinal rim volume of the ONH and the average RNFL thickness. The surrogates used for cognitive function were the paired associates learning test (PAL), level of education, grade point average (GPA) and Humphrey 24–2 perimetric test time (HFA). We did exploratory research between the ophthalmological parameters and the surrogates for cognition and the correlations between the surrogates for cognition. Results: We found that a larger disc area was associated with a higher level of education, faster accomplishment of the HFA (R = −0.065) but a lower GPA (R = −0.084). An increase in neuroretinal rim volume was associated with fewer errors in the PAL test (R = −0.056), higher level of education, higher GPA (R = 0.072) and faster accomplishment of the HFA (R = −0.047). A thicker RNFL was associated with faster accomplishment of the HFA (R = −0.047). Conclusion: We were able to find statistically significant associations between the parameters of the optic nerve head, the RNFL and cognition in the NFBC Eye study. However, the correlations were negligible at best and of limited predictive value.

AimTo assess the applicability of a structure–function (S-F) analysis combining spectral-domain optical coherence tomography (SD-OCT) and standard automated perimetry (SAP) in glaucoma screening in a middle-aged population.MethodsA randomised sample of 3001 Caucasian participants aged 45–49 years of the Northern Finland Birth Cohort Eye Study was examined. We performed an eye examination, including 24–2 SAP, optic nerve head (ONH) and retinal nerve fibre layer (RNFL) photography and SD-OCT of the peripapillary RNFL. The S-F report was generated by Forum Glaucoma Workplace software. OCT, SAP and the S-F analysis were evaluated against clinical glaucoma diagnosis, that is, the positive ‘2 out of 3’ rule based on the clinician’s evaluation of ONH and RNFL photographs and visual fields (VFs).ResultsAt a specificity of 97.5%, the sensitivity for glaucomatous damage was 26% for abnormal OCT, 35% for SAP and 44% for S-F analysis. Estimated areas under the curve were 0.74, 0.85 and 0.76, and the corresponding positive predictive values were 8 %, 10% and 12%, respectively. By applying a classification tree approach combining OCT, SAP and defect localisation data, a sensitivity of 77% was achieved at 90% specificity. In a localisation analysis of glaucomatous structural and functional defects, the correlation with glaucoma increased significantly if the abnormal VF test points were located on borderline or abnormal OCT zones.ConclusionSAP performs slightly better than OCT in glaucoma screening of middle-aged population. However, the diagnostic capability can be improved by S-F analysis.

BackgroundOnly a few studies reporting the long-term outcome of children with idiopathic tubulointerstitial nephritis (TIN) and uveitis syndrome (TINU) are available. We studied the long-term kidney and ocular outcome in a nationwide cohort of children with TIN or TINU.MethodsAll patients followed up for a minimum of 1 year by a paediatrician and an ophthalmologist were enrolled. The data on plasma creatinine (P-Cr), estimated glomerular filtration rate (eGFR), proteinuria, hypertension and uveitis were collected retrospectively.ResultsFifty-two patients were studied. Median age at time of diagnosis was 13.1 (1.8–16.9) years and median follow-up time was 5.7 (1.1–21.2) years. Forty-five (87%) patients were initially treated with glucocorticoids. The median of the maximum P-Cr was 162 μmol/l (47–1,016) and that of eGFR 47 ml/min/1.73m2(8–124). Uveitis was diagnosed in 33 patients (63%) and 21 (40%) patients developed chronic uveitis. P-Cr normalised in a median of 2 months. Eleven (21%) patients had nephritis recurrence during or after discontinuation of glucocorticoids. At the latest follow-up, 13 (25%) patients had eGFR < 90 ml/min/1.73m2(median 83; 61–89 ml/min/1.73m2). Six patients had tubular proteinuria; all presented with TIN without uveitis. Seven (13%) patients were hypertensive. Eleven (21%) patients had uveitis. One patient developed uraemia and was later transplanted.ConclusionsOur study questions the previously reported good long-term kidney and ocular outcome of patients with TIN/TINU. Decreased kidney function and/or ocular co-morbidities may persist for several years; thus, both kidney and ocular follow-up for at least 1 year is warranted.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Diabetic retinopathy is a microvascular complication of hyperglycaemia. Little is known about the association of glucose metabolism and retinopathy signs in the non-diabetic middle-aged population. We studied prevalence of retinopathy in a subsample of Northern Finland Birth Cohort study (NFBC1966) of 1809 subjects, at 47 years of age, without previously diagnosed type 2 diabetes and/or blood pressure-lowering medication. All participants underwent clinical evaluations including an oral glucose tolerance test (glucose and insulin values measured at 0, 30, 60 and 120 min) and HbA1c. The retinopathy signs were diagnosed by fundus photographs and classified according to the Eurodiab classification scheme. The overall prevalence of newly diagnosed retinopathy was 1.4%. The retinopathy signs were significantly associated with increased 30 min, 1-h and 2-h glucose levels and 2-h insulin level in an OGTT. After adjustment with systolic blood pressure, only 30 min glucose, 1-h glucose and 2-h insulin levels were associated with retinopathy signs. Our findings show the potential role of 30 min and 1-h post-load glucose and 2-h insulin levels as risk factors for retinopathy lesions among the participants without previously diagnosed diabetes or hypertensive medication.

Background/AimThe aim of this study was to evaluate the effect of prediabetes and diabetes on macular thickness and retinal vascular calibres in our population-based cohort (Northern Finland Birth Cohort).MethodsThe population of 2005 individuals was divided into diabetes (n=57), prediabetes (n=1638) and normal glucose metabolism (NGM) groups (n=310). Total thickness of the macula was measured using Cirrus HD-OCT 4000. Central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) calibres were measured from the fundus images. The diagnosis of diabetes and prediabetes was made according to WHO 2006 diagnostic standards.ResultsSignificant macular thinning was observed in subjects with prediabetes (−2.69 μm (95% CI −4.29 to −1.09), p3 (95% CI −0.16 to −0.04), pConclusionWe detected significant thinning of the macula in subjects with prediabetes. The diameters of retinal arteries were decreased by impaired glucose metabolism. This study provides a new perspective since it revealed that the early and subtle changes caused by prediabetes as macular thinning had significant ACME on retinal vessels, therefore supporting the neurodegenerative theory of diabetes-induced changes in the retina.

To evaluate visual acuity (VA) and visual fields (VF) quantitatively before and after endoscopic transsphenoidal surgery (ETS), with special attention to prognostic factors such as the pituitary adenoma (PA) suprasellar extension (SSE), volume and the patients' age.Medical records of 47 patients with PA undergoing ETS were evaluated. VA, VF, preoperative visual impairment score (VISpre) and postoperative visual impairment score (VISpost) were determined. The PA SSE, volume, chiasmal contact, and their correlation with visual function were assessed preoperatively and postoperatively.The final cohort included 47 patients. VA improved in 54 of 76 eyes (71.0%) after ETS, and 69 of 76 eyes (90.7%) gained normal VA. Postoperative VF recovery occurred in 32 of 37 eyes (86.5%). The mean change in VIS was 12.0 (95% confidence interval [CI], 7.7-16.3) and improved in all patients with tumor-related visual impairment (n = 25). However, visual outcome was poorer when VISpre was greater than 40. When VISpre was 21-40, age linearly correlated with VIS improvement (P = 0.03); younger patients had satisfactory and older poorer visual outcome. The mean SSE in patients with VF defects (n = 20) was 16.6 mm (95% CI, 13.3-19.9). Mean SSE in patients with no VF defects (n = 23) was 6.6 mm (95% CI, 4.9-8.3; P 0.001), and the cutoff value for visual perturbations was 9.5 mm for SSE and 8.6 mL for PA volume (P0.001 for both).The visual outcome after ETS for PAs was excellent, and serious complications were rare. Severe preoperative visual impairment resulted in poorer postoperative visual outcomes. The SSE of the PA was the most important predictor of visual outcome after ETS.

AimsStudying the relationship between retinal vessel diameter (RVD) with (1) macular thickness and volume, (2) retinal nerve fibre layer (RNFL), (3) ganglion cell-inner plexiform layer (GC-IPL) and (4) optic nerve head (ONH) in a population cohort of middle-aged Caucasians.MethodsWe collected data from 3070 individuals. We used a semiautomated computer-assisted programme to measure central retinal arteriolar equivalent and central retinal venular equivalent. Macular and ONH parameters were assessed by optical coherence tomography.ResultsData from 2155 persons were analysed. A larger RVD was associated with a thicker macula and increased macular volume; each SD increase in average macular thickness and volume was associated with a 3.28 µm and a 3.19 µm increase in arteriolar diameter and a 5.10 µm and a 5.08 µm increase in venular diameter, respectively (pConclusionsIncreased macular thickness, macular volume, GC-IPL thickness, RNFL thickness and optic nerve rim area were associated with larger RVDs in all subjects. This study clarified the anatomical correlations between both macular and ONH parameters with RVD for middle-aged Caucasians; these can represent a basis for further studies investigating the vascular aetiology of eye diseases.

AimTo evaluate the applicability of imaging devices (spectral-domain optical coherence tomography (Cirrus SD-OCT), scanning laser polarimetry (GDx) and scanning laser ophthalmoscopy (Heidelberg Retinal Tomograph, HRT3)) for glaucoma screening in a middle-aged unselected population.MethodsParticipants of the population-based Northern Finland Birth Cohort Eye Study, aged 45 to 49 years, underwent a comprehensive eye examination including modern imaging with five methods (retinal nerve fibre layer (RNFL) and macular ganglion cell layer +inner plexiform layer (GCIPL) analysis and their combination with SD-OCT, GDx and HRT). The performance of the automated classification of the imaging devices was assessed using a clinical glaucoma diagnosis as reference, that is, the ‘2 out of 3’ rule based on the evaluation of optic nerve head and RNFL photographs and visual fields.ResultsWe examined 6060 eyes of 3039 subjects; in the clinical evaluation, glaucomatous damage was found in 33 subjects (1.1%) in 43 eyes. The following sensitivities were obtained; RNFL analysis (53%), GCIPL analysis (50%), OCT combination analysis (61%), GDx (56%) and HRT (31%) with corresponding specificities of 95%, 92%, 90%, 88% and 96%. The area under the curve values were 0.76, 0.73, 0.75, 0.75 and 0.73, respectively. Post-test probabilities of glaucoma after positive imaging finding with each of these methods in this unselected population were 11%, 7%, 6%, 5% and 7%, respectively.ConclusionScreening capabilities of the OCT, GDx and HRT were rather similar. The accuracy of all evaluated parameters was only moderate and thus screening with these parameters alone is not reliable.

Background Tubulointerstitial nephritis (TIN) and uveitis syndrome (TINU) are likely to be autoimmune diseases. Based on previous studies, adults with isolated idiopathic uveitis have polymorphisms in interleukin 10 (IL-10) and tumor necrosis factor a (TNF-alpha) genes. We aimed to evaluate the presence of IL-10 and TNF-alpha polymorphisms in a nationwide cohort of pediatric TIN/TINU patients. Methods Single nucleotide polymorphisms in IL-10 (+434T/C, +504G/T, -1082G/A, -2849C/T) and in TNF alpha (-308G/A, -238G/A, -857C/T) genes were genotyped in 30 well-defined pediatric patients with idiopathic TIN/TINU syndrome. Control group frequencies for these SNPs were obtained from 393 independent Finnish subjects. Results The homozygous minor allele in IL-10 +434T (rs2222202) and IL-10+504G (rs3024490) was found in all patients with TIN or TINU syndrome while the frequency of these minor alleles in the control population was 44% and 23%, respectively (p

Purpose To report the prevalence of glaucoma in the Northern Finland Birth Cohort (NFBC) Eye Study. Methods Subjects of the population-based Northern Finland 1966 Birth Cohort (NFBC), aged 45-49 years at the time of the field examination, were randomized to eye screening (50%) and control (50%) groups. The eye examination protocol included best corrected visual acuity (BCVA), measurements of intraocular pressure and central corneal thickness, Humphrey 24-2 perimetry, stereoscopic optic nerve head (ONH) and retinal nerve fibre layer (RNFL) photography and imaging with optical coherence tomography (OCT), scanning laser polarimetry (GDx) and scanning laser ophthalmoscopy (HRT). The diagnosis of glaucoma was made by two independent general ophthalmologists and three independent glaucoma experts based on the evaluation of the ONH and RNFL photographs and the visual fields. Results Totally, 10 321 subjects of the NFBC main study were alive in Finland in 2011, and they were randomized to the NFBC Eye Study group (n = 5155) and the control group (n = 5166). Of the randomized subjects, 3039 of 5155 (59%) responded and had sufficient data for the study. Glaucoma was suspected in 172 subjects (5.7%) at the first phase of the evaluation protocol. The interobserver agreement between two screening ophthalmologists was moderately good (kappa value 0.54 [95% confidence intervals (CI) 0.46-0.61]). Finally, definite glaucoma was found in 33 subjects (1.1% [95% CI 0.8-1.5]). Conclusion The study provides up-to-date information on the prevalence of glaucoma in a middle-aged Caucasian population in Finland. The baseline data reported here allows the evaluation of the cost-effectiveness of screening later on.

Amblyopia is a common visual disorder that is treatable in childhood. However, therapies have limited efficacy in adult patients with amblyopia. Fluoxetine can reinstate early-life critical period-like neuronal plasticity and has been used to recover functional vision in adult rats with amblyopia. We conducted a Phase 2, randomized (fluoxetine vs. placebo), double-blind, multicenter clinical trial examined whether or not fluoxetine can improve visual acuity in amblyopic adults. This interventional trial included 42 participants diagnosed with moderate to severe amblyopia. Subjects were randomized to receive either 20 mg fluoxetine (n = 22) or placebo (n = 20). During the 10-week treatment period, all subjects performed daily computerized perceptual training and eye patching. At the primary endpoint, the mean treatment group difference in visual acuity improvement was only 0.027 logMAR units (95% CI: −0.057 to 0.110; p = 0.524). However, visual acuity had significantly improved from baseline to 10 weeks in both fluoxetine (−0.167 logMAR; 95% CI: −0.226 to −0.108; p

Purpose: The evaluation of visual acuity (VA) and refraction in the Northern Finland Birth Cohort Eye study was performed using the Nidek AR-360A autorefractometer. The accuracy of the method for this population-based screening study was assessed. Methods: Measurements of the refractive error were obtained from the right eyes of 1238 subjects (mean age 47), first objectively with the AR-360A and then subjectively by an optometrist. Agreement with the subjective refraction was calculated for sphere, cylinder, mean spherical equivalent (MSE), cylindrical vectors J₄₅ and J₀ and presbyopic correction (add). Visual acuity (VA) was measured using an ETDRS chart and the autorefractometer. Results: The refractive error measured with the AR-360A was higher than the subjective refraction performed by the optometrist for sphere (0.007 D ± 0.24 D p = 0.30) and also for cylinder (−0.16 D ± 0.20 D p < 0.0005). The bias between the measurements of MSE, J₄₅ and J₀ was low: −0.07 D ± 0.22 D (p = 0.002), 0.01 D ± 0.43 D (p = 0.25) and −0.01 D ± 0.42 D (p = 0.43), respectively. The amount of add measured by the autorefractometer was higher than the subjective 0.35 D ± 0.29 D (p < 0.0005). There was a statistically significant correlation between VA (p < 0.0005) and the difference between the subjective and objective refraction. In 99.2% of the measurements, visual values were within one decimal line of each other. Conclusion: The Nidek AR-360A autorefractometer is an accurate tool for determining the refraction and VA in a clinical screening trial.

Purpose To determine the ability of ophthalmologists across Europe to match stereoscopic optic disc photographs to visual fields of varying severity. Design Evaluation and comparison of 2 diagnostic tests. Participants A total of 109 of 260 invited ophthalmologists in 11 European countries. These had participated in the previous European Optic Disc Assessment Trial (EODAT), a trial on glaucoma diagnostic accuracy based on optic discs only. Methods Each participant matched stereo optic disc photographs of 40 healthy and 48 glaucomatous eyes to a visual field chosen from 4 options per disc. The 4 presented visual fields included the corresponding one and 3 other visual fields, varying in severity. The matching accuracy and any inaccuracy per disease severity were calculated. Classification accuracy (as glaucomatous or healthy) was compared with EODAT data. Duplicate slides allowed for the assessment of intraobserver agreement. Main Outcome Measures Accuracy of matching optic discs with their corresponding visual field and of classifying them as healthy or glaucomatous; intraobserver agreement (κ). Results The overall accuracy of ophthalmologists for correctly matching stereoscopic optic disc photographs to their visual fields was 58.7%. When incorrectly matched, the observers generally overestimated the visual field severity ( P Conclusions European ophthalmologists correctly matched stereoscopic optic disc photographs to their corresponding visual field in only approximately 59% of cases. In most mismatches, the clinicians overestimated the visual field damage. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Purpose: The purpose of this study was to determine whether exercise affects the stereometric parameters representing optic nerve head (ONH) topography. Methods: ONH topography, intraocular pressure (IOP) and blood pressure of 30 healthy volunteers were monitored before, during and after dynamic exercise raising systolic blood pressure by a minimum of 30 mmHg. Change in the stereometric ONH parameters was calculated. Results: IOP decreased and blood pressure increased during exercise, resulting in an increase in mean ocular perfusion pressure. Exercise was associated with an increase in variance in 17 of the 18 stereometric ONH parameters. The increase in variance was statistically significant in eight parameters, including rim area, cup/disc area ratio and cup shape measure. There was no statistically significant change in image quality. The absolute change from baseline in rim area, cup area, cup/disc area ratio, rim/disc area ratio and rim volume showed a statistically significant (p

Transient monocular visual loss (TMVL) usually is due to hypoperfusion of the optic nerve or retinal circulation. After the exclusion of thromboembolic and carotid artery diseases, retinal vasospasm should be considered as an underlying cause of TMVL. We report a patient with an increasing number of transient attacks of unilateral blindness. Vasospasm was confirmed as the etiology by fundus photography during an attack. Nifedipine 10 mg/d decreased the severity of the visual loss and the number of attacks. The patient was relieved of symptoms entirely with a nifedipine dose of 20 mg/d.

Acute idiopathic tubulointerstitial nephritis (TIN) is considered a condition with a good long-term prognosis. However, there is evidence that some patients develop permanent renal impairment. The aim of this study was to evaluate the clinical characteristics of TIN at the time of diagnosis in children and determine whether the findings upon presentation predict renal outcome. The clinical data and biopsy findings from 26 children with idiopathic TIN admitted to four Finnish university hospitals were analyzed retrospectively. Twenty-five patients (96%) manifested renal insufficiency. After the mean follow-up time of 2.75 years (SD 2.5; 0.9-13.5), 4 patients (15%) had permanent renal insufficiency and 8 patients (31%) had persistent low-molecular weight proteinuria. Uveitis was found in 12 patients (46%). Four of these patients (33%) developed chronic uveitis. Our analysis showed that none of the laboratory or biopsy findings upon presentation prognosticated renal outcome. No correlation between renal disease and uveitis could be found either. The occurrence of uveitis among TIN patients was higher than previously reported. Uveitis may develop late and without recurrence of renal dysfunction. Therefore, follow-up by a pediatrician and by an ophthalmologist is warranted in children with acute TIN for at least 12 months from diagnosis.

Desorption atmospheric pressure photoionization-mass spectrometry (DAPPI-MS) is a versatile surface analysis technique for a wide range of analytes, especially for neutral and non-polar analytes. Here, a set of analytes typically found in environmental or food samples was analyzed by DAPPI-MS. The set included five polyaromatic hydrocarbons (PAHs), one N-PAH, one brominated flame retardant, and nine pesticides, which were studied with three different spray solvents: acetone and toluene in positive ion mode, and anisole in negative ion mode. The analytes showed [M + H](+), M(+*), and [M-H](-) ions as well as fragmentation and substitution products. Detection limits for the studied compounds ranged from 30 pg to 1 ng (from 0.14 to 5.6 pmol). To demonstrate the feasibility of the use of DAPPI-MS two authentic samples - a circuit board and orange peel - and a spiked soil sample were analyzed. Tetrabromobisphenol A, imazalil, and PAHs were observed from the three above-mentioned samples, respectively. The method is best suited for rapid screening analysis of environmental or food samples.

A new integrated microchip for liquid chromatography–mass spectrometry (LC–MS) is presented. The chip is made from bonded silicon and glass wafers with structures for a packed LC column channel, a micropillar frit, a channel for optional optical detection, and a heated vaporizer section etched in silicon and platinum heater elements on the glass cover. LC eluent is vaporized and mixed with nebulizer gas in the vaporizer section and the vapor is sprayed out from the chip. Nonpolar and polar analytes can be efficiently ionized in the gas phase by atmospheric pressure photoionization (APPI) as demonstrated with polycyclic aromatic hydrocarbons (PAHs) and selective androgen receptor modulators (SARMs). This is not achievable with present LC–MS chips, since they are based on electrospray ionization, which is not able to ionize nonpolar compounds efficiently. The preliminary quantitative performance of the new chip was evaluated in terms of limit of detection (down to 5 ng mL−1), linearity (r > 0.999), and repeatability of signal response (RSD = 2.6–4.0%) and retention time (RSD = 0.3–0.5%) using APPI for ionization and PAHs as standard compounds. Determination of fluorescent compounds is demonstrated by using laser-induced fluorescence (LIF) for detection in the optical detection channel before the vaporizer section.

This study presents thermal silicon microbridge actuators which have been made by a novel fabrication process utilizing dry processes for all critical steps. The fabrication process results in microbridges which are fully oxide covered, with excellent surface quality and dimensional control. The microbridges are made in the device layer of a silicon-on-insulator (SOI) wafer which ensures uniform doping profile and accurate thickness control. The electrical and mechanical responses of the bridges were measured upon rapid heating up to near the melting point of silicon. Up to 12 μm mechanical deflection due to thermal expansion was detected by white light interferometry (WLI) which allowed accurate measurement. Mechanical deflection has previously not been measured for silicon microlamps. Thermal conduction in the air gap between the actuator and the neighbouring solid silicon parts was analysed and shown to be more important than convection or radiation, even at very high operation temperatures.

The factors influencing desorption and ionization in newly developed desorption atmospheric pressure photoionization-mass spectrometry (DAPPI-MS) were studied. Redirecting the DAPPI spray was observed to further improve the versatility of the technique: for dilute samples, parallel spray with increased analyte signal was found to be the best suited, while for more concentrated samples, the orthogonal spray with less risk for contamination is recommended. The suitability of various spray solvents and sampling surface materials was tested for a variety of analytes with different polarities and molecular weights. As in atmospheric pressure photoionization, the analytes formed [M + H](+), [M - H](-), M(+*), M(-*), [M - H + O](-), or [M - 2H + 2O](-) ions depending on the analyte, spray solvent, and ionization mode. In positive ion mode, anisole and toluene as spray solvents promoted the formation of M(+*) ions and were therefore best suited for the analysis of nonpolar compounds (anthracene, benzo[a]pyrene, and tetracyclone). Acetone and hexane were optimal spray solvents for polar compounds (MDMA, testosterone, and verapamil) since they produced intensive [M + H](+) ion peaks of the analytes. In negative ion mode, the type of spray solvent affected the signal intensity, but not the ion composition. M(-*) ions were formed from 1,4-dinitrobenzene, and [M - H + O](-) and [M - 2H + 2O](-) ions from 1,4-naphthoquinone, whereas acidic compounds (naphthoic acid and paracetamol) formed [M - H](-) ions. The tested sampling surfaces included various materials with different thermal conductivities. The materials with low thermal conductivity, i.e., polymers like poly(methyl methacrylate) and poly(tetrafluoroethylene) (Teflon) were found to be the best, since they enable localized heating of the sampling surface, which was found to be essential for efficient analyte desorption. Nevertheless, the sampling surface material did not affect the ionization mechanisms.

Purpose: To determine the Heidelberg retina tomograph (HRT) parameters that identify glaucomatous changes in optic nerve head (ONH) topography associated with progression of retinal nerve fibre layer (RNFL) defects. Methods: A total of 68 eyes with open-angle glaucoma were included in this retrospective study: 34 eyes showed progression of an RNFL defect during the follow-up period and 34 eyes did not. Successful RNFL photographs and scanning laser tomography examinations with the HRT were taken in all patients at each of three visits. The change in HRT parameter values during follow-up was calculated. Results: Progression of the RNFL defect was statistically significantly correlated (p = 0.049) with only one topographic ONH parameter, the cup shape measure. The best combination of two parameters (p = 0.009) included the maximum cup depth and the linear cup : disc area ratio; the best combination of three parameters (p = 0.007) included the maximum cup depth, the linear cup : disc area ratio and the horizontal cup : disc area ratio. Sensitivity and specificity values were 52.9% and 73.5%, respectively, for the cup shape measure, 70.6% and 73.5%, respectively, for the two-parameter combination, and 76.5% and 79.4%, respectively, for the three-parameter combination. The areas under the receiver operating characteristic curve were 0.617, 0.724 and 0.753, respectively. Conclusions: The results indicate that the HRT parameters may be used to detect small ONH changes associated with progression of the RNFL defect. With the exception of the cup shape measure, the parameters which provide the best correlation with progression differ from those considered optimal for recognizing the presence or absence of glaucoma.

Purpose: Tafluprost is a new prostaglandin F2α (PGF2α) derivative in development for the treatment of glaucoma. Tafluprost is the first PGF2α analogue with a preservative-free formulation. Methods: This randomized, investigator-masked, multicentre, crossover phase III study evaluated the pharmacodynamics and safety of preserved and preservative-free tafluprost 0.0015% eyedrops administered for 4 weeks in 43 patients with open-angle glaucoma or ocular hypertension. The primary variable was change from baseline in overall diurnal intraocular pressure (IOP) at 4 weeks. Adverse events and other safety parameters were also analysed. Results: Decreased IOP was clearly observed with both formulations at week 1 and was sustained until week 4. The overall treatment difference (preservative-free versus preserved formulations) at week 4 was 0.01 mmHg (95% confidence interval − 0.46 to 0.49; p = 0.96). There were no unexpected safety-related findings. Both formulations were well tolerated and most adverse events were ocular and mild in severity. Conclusions: The reduction in IOP achieved by preservative-free tafluprost is equivalent to that obtained with the preserved formulation. The preservative-free formulation was generally well tolerated.

The first microchip version of sonic spray ionization (SSI) as an atmospheric pressure ionization source for mass spectrometry (MS) is presented. The microchip used for SSI has recently been developed in our laboratory, and it has been used before as an atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI) source. Now the ionization is achieved simply by applying high (sonic) speed nebulizer gas, without heat, corona discharge, or high voltage. The microchip SSI was applied to the analysis of tetra-N-butylammonium, verapamil, testosterone, angiotensin I, and ibuprofen. The limits of detection were in the range of 15 nM to 4 microM. The technique was found to be highly dependent on the position of the chip toward the mass spectrometer inlet, and on the gas and the sample solution flow rates. The microchip SSI provided dynamic linearity following a pattern similar to that used with electrospray, good quantitative repeatability (RSD=16%), and long-term signal stability.

Purpose A clinical evaluation of the Nidek AR-360A autorefractometer was performed to examine its accuracy in measuring refraction and visual acuity, in a pilot study for a clinical screening trial (the Northern Finland Birth Cohort Eye Study). Methods Measurements of the refractive error were obtained from 160 eyes of 80 subjects (mean age 48.9), first objectively with the AR-360A and then subjectively by an optometrist. Agreement with the subjective refraction was calculated for sphere, cylinder, mean spherical equivalent (MSE), cylindrical vectors J45 and J0, and presbyopic correction (add). Visual acuity was measured using an ETDRS chart and the autorefractometer. The central corneal thickness (CCT) was measured with pachymetry. Results The refractive error measured with the AR-360A was lower than the subjective refraction performed by the optometrist for sphere (−0.13D ± 0.31D p

The up-date of the Finnish Current Care Guideline for glaucoma is based primarily on systematic reviews searched up by March 2014. The recommendations are presented in nine tables, which are based on 95 graded statements with evidence summaries. The online availability (www.kaypahoito.fi) of the English translation of guideline and evidence summaries enables the verification of the evidence and recommendations. Ten external stakeholders gave a mean value of 1.8 (range of 1 = completely agree to 4 = completely disagree) for the structured questions (e.g. definitions, goals, questions, target users) and judged the evidence and the recommendations.

A microfabricated re-usable multi-inlet fluidic connector chip in PDMS (polydimethylsiloxane) is introduced. A connector takes up ca. 1 mm 2 area and inlet density is limited principally by capillary tubing dimensions. Anisotropically etched silicon mold, with patterns matching those of the microfluidic chip, and dummy fibers have been used in PDMS casting. The connector chip material is self-sealing PDMS, which eliminates the need for gluing. This feature enables tubing to be attached and removed repeatedly, as long as the PDMS surfaces in contact with the microfluidic chip remain clean. Both imide-coated glass capillaries and polymeric PEEK (polyetheretherketone) tubes have been successfully connected to a microfluidic nebulizer chip which has one liquid and two gas ports. The connections were measured to withstand overpressures up to 220 and 20 kPa with and without additional compression, respectively. The fact that the connector chip is fabricated independently of the microfluidic chip improves significantly assembly yield of the fluidic system, because the microfluidic chip is not subject to gluing or other assembly operations. We tested the PDMS chip successfully with the nebulizer chip in mass spectrometry application. Even though room temperature performance of the connector chip was excellent, at elevated temperatures (above 50 °C) significant background signal originating from PDMS can be seen in mass spectra. This limits the usability of PDMS parts in sensitive mass spectrometry applications.

A miniaturized nebulizer chip for capillary liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (capillary LC-microchip APCI-MS) is presented. The APCI chip consists of two wafers, a silicon wafer and a Pyrex glass wafer. The silicon wafer has a DRIE etched through-wafer nebulizer gas inlet, an edge capillary insertion channel, a stopper, a vaporizer channel and a nozzle. The platinum heater electrode and pads for electrical connection were patterned on to the Pyrex glass wafer. The two wafers were joined by anodic bonding, creating a microchip version of an APCI-source. The sample inlet capillary from an LC column is directly connected to the vaporizer channel of the APCI chip. The etched nozzle in the microchip forms a narrow sample plume, which is ionized by an external corona needle, and the formed ions are analyzed by a mass spectrometer. The nebulizer chip enables for the first time the use of low flow rate separation techniques with APCI-MS. The performance of capillary LC-microchip APCI-MS was tested with selected neurosteroids. The capillary LC-microchip APCI-MS provides quantitative repeatability and good linearity. The limits of detection (LOD) with a signal-to-noise ratio (S/N) of 3 in MS/MS mode for the selected neurosteroids were 20-1000 fmol (10-500 nmol l(-1)). LODs (S/N = 3) with commercial macro APCI with the same compounds using the same MS were about 10 times higher. Fast heat transfer allows the use of the optimized temperature for each compound during an LC run. The microchip APCI-source provides a convenient and easy method to combine capillary LC to any API-MS equipped with an APCI source. The advantages and potentials of the microchip APCI also make it a very attractive interface in microfluidic APCI-MS.

PURPOSE To evaluate the correlation of the change in glaucoma probability score (GPS) and the stereometric optic nerve head (ONH) parameters of the Heidelberg Retina Tomograph (HRT)3 to an event of glaucomatous progression observed with stereoscopic ONH photography. METHODS The subjects for this retrospective follow-up study were monitored with the HRT and stereoscopic ONH photographs. Stable, high-quality imaging and at least 18 months of follow-up was required. The topography examinations were acquired using HRT II and calculated with HRT3 software. The event of progression was determined by masked evaluation of stereoscopic ONH photographs. RESULTS A total of 476 eyes of 342 subjects met the inclusion criteria. All the examinations with HRT II were backwards compatible with either the GPS or the stereometric parameters of HRT3. The highest statistical significance for the correlation with progression was observed in the change in cup volume and cup:disc area ratio (p

Patients with tubulointerstitial nephritis (TIN) may develop permanent renal impairment. However, there are no prospective studies available on the treatment of TIN.The effect of prednisone in the treatment of TIN was evaluated in a total of 17 patients who received prednisone or who were followed up without medication. The patient group was subdivided based on the initial plasma creatinine (PCr), below or above 150 μmol/l.All prednisone-treated patients had normal plasma creatinine (PCr) after 1 month of treatment (median 59.1 [45-85] μmol/l) whereas only 50 % of patients in the non-treatment group had normal creatinine (median 81.0 [42-123] μmol/l) at the same time point (p = 0.025). During 6 months' follow-up, PCr decreased in all patient groups; however, it decreased significantly only in prednisone-treated patients with baseline PCr150 μmol/l (p0.001). At the end of follow-up, no difference in PCr, glomerular filtration rate (GFR), or low molecular weight (LMW) proteinuria could be found between the study groups. A considerable number of patients in both groups had subnormal GFR and/or persistent LMW proteinuria at the 6-month follow-up visit. Eighty-two percent of the patients had uveitis.Prednisone speeds up the recovery from renal symptoms of TIN, especially in patients with severe nephritis. The renal function did not differ significantly between prednisone and control patients after 6 months' follow-up.

Purpose To evaluate the occurrence and characteristics of uveitis related to tubulointerstitial nephritis (TIN) in children. Design Prospective, observational, multicenter, partly placebo-controlled treatment trial. Participants Nineteen children with a biopsy-proven TIN. Methods Patients were treated with prednisone or followed without treatment. In addition to the nephrologic evaluations, the prospective follow-up included structured ophthalmological examinations at the onset of TIN and at 3 and 6 months after the diagnosis. Main Outcome Measures Occurrence, clinical features, and outcome of uveitis. Results Some 84% (16/19) of the patients had uveitis, 83% (5/6) in the nontreatment group and 82% (9/11) in the prednisone-treated group. The remaining 2 patients, originally in the nontreatment group, were switched to the prednisone group after 2 weeks. Both of them developed uveitis. Altogether, 3 patients developed uveitis during prednisone treatment and 2 patients showed worsening of uveitis despite the systemic corticosteroid. Some 50% (8/16) of the patients with uveitis presented with no ocular symptoms; 88% (14/16) of the patients had a chronic course of uveitis. Two patients were diagnosed with uveitis before nephritis; nephritis and uveitis were diagnosed within 1 week from each other in 7 patients, and uveitis developed 1 to 6 months after the diagnosis of TIN in 7 patients. Conclusions There was no statistically significant difference in the occurrence of uveitis in patients with TIN in the prednisone and nontreatment groups. In this study, the occurrence of uveitis associated with TIN was considerably higher than previously reported. Uveitis related to TIN may develop late and is often asymptomatic. The ophthalmological follow-up of all patients with TIN is warranted for at least 12 months starting with 3-month intervals. Financial Disclosure(s) The authors have no proprietary or commercial interest in any material discussed in this article.

Purpose The purpose of this study was to determine whether phacoemulsification cataract surgery with intraocular lens (IOL) implantation has an effect on measuring optic nerve head (ONH) topography using the Heidelberg Retina Tomograph (HRT). Methods The study population inculuded 31 women and 12 men aged 59-81 years with no previous history of eye diseases, surgery, laser procedures or medication. The patients underwent first-eye cataract surgery for senile cataract. HRT II with software version 1.6 was used to obtain three-dimensional images of the ONH as a part of a meticulous eye examination. The quality of the HRT image was assessed using topography standard deviation (TSD). The topography measurements are considered unreliable if TSD is more than 50 µm. Re-examination took place one month after surgery. Results Before surgery the topography measurements were unreliable in 33% (14/43) of the eyes; in 4 of these cases ONH topography could not be calculated at all. One month after cataract surgery the ONH topography could be calculated in all eyes and only one had unreliable topography measurements. The mean TSD was 39 µm before and 22 µm after surgery when calculated for all eyes with measurable topographies. The change in the TSD was statistically significant (p

A new and sensitive analytical method, using capillary liquid chromatography (capLC) with a microfabricated heated nebulizer chip for atmospheric pressure photoionization and tandem mass spectrometry (μAPPI-MS/MS), was developed for the analysis of selected carbamate pesticides in a tomato matrix. The performance of the instrumental method was evaluated, using seven pesticides, namely oxamyl, methomyl, aldicarb, carbofuran, pirimicarb, thiocarb, and ditalimfos. The limits of detection achieved with the capLC-μAPPI-MS/MS method in the positive ion mode were low, ranging from 0.25 ng mL(-1) for pirimicarb to 5 ng mL(-1) for oxamyl and methomyl, corresponding to 5 and 0.25 μg kg(-1) for tomato samples, respectively, which are clearly below the maximum residue limits for them in fruits and vegetables. The repeatability of the instrumental method ranged from 2.9 to 13.9% (RSD) at a low (0.05 μg mL(-1)) concentration level. An adequate linearity (r(2)=0.984-0.999) at a concentration range from 0.005 to 5.0 μg mL(-1) was observed for all pesticides. The results obtained show that the capLC-μAPPI-MS/MS method developed could be used for the analysis of selected pesticides from tomato.

Purpose: To evaluate the factors affecting the sensitivity and specificity of the stereometric optic nerve head (ONH) parameters of the Heidelberg Retina Tomograph (HRT) to glaucomatous progression in stereoscopic ONH photographs. Methods: The factors affecting the sensitivity and specificity of the vertical cup : disc ratio, the cup : disc area ratio, the cup volume, the rim area and a linear discriminant function to progression were analysed. These parameters were the best indicators of progression in a retrospective study of 476 eyes. The reference standard for progression was the masked evaluation of stereoscopic ONH photographs. Results: The factors having the most significant effect on the sensitivity and specificity of the stereometric ONH parameters were the reference height difference and the mean topography standard deviation (TSD), indicating image quality. Also, the change in the TSD and age showed consistent, but variably significant, influence on all parameters tested. The sensitivity and specificity improved when there was little change in the reference height, the image quality was good and stable, and the patients were younger. The sensitivity and specificity of the vertical cup : disc ratio was improved by a large disc area and high baseline cup : disc area ratio. The rim area showed a better sensitivity and specificity for progression with a small disc area and low baseline cup : disc area ratio. Conclusion: The factors affecting the sensitivity and specificity of the stereometric ONH parameters to glaucomatous progression in disc photographs are essentially the same as those affecting the measurement variability of the HRT.

We examined the feasibility of capillary liquid chromatography/microchip atmospheric pressure photoionization tandem mass spectrometry (capLC/microAPPI-MS/MS) for the analysis of anabolic steroids in human urine. The urine samples were pretreated by enzymatic hydrolysis (with beta-glucuronidase from Helix pomatia), and the compounds were liquid-liquid extracted with diethyl ether. After separation the compounds were vaporized by microchip APPI, photoionized by a 10 eV krypton discharge lamp, and detected by selected reaction monitoring. The capLC/microAPPI-MS/MS method showed good sensitivity with detection limits at the level of 1.0 ng mL(-1), good linearity with correlation coefficients between 0.9954 and 0.9990, and good repeatability with relative standard deviations below 10%. These results demonstrate that microchip APPI combined with capLC/MS/MS provides a new potential method for analyzing non-polar and neutral compounds in biological samples.

To determine the sensitivity and specificity of the stereometric optic nerve head (ONH) parameters of the Heidelberg Retina Tomograph (HRT) to detect an event of progression verified in serial stereoscopic ONH photography.A retrospective study of 476 eyes of 342 patients with more than 18 months of follow-up with successful stereoscopic ONH photography was conducted. All eyes had good-quality HRT examinations with perfect image alignment. 51 (11%) eyes showed progression in the stereoscopic ONH photographs between visits. The photographs were evaluated by experienced masked observers, whose interobserver agreement (kappa) varied between 0.403 and 0.510.The change in most (13/22) of the stereometric ONH parameters showed a statistically significant correlation with progression. The parameter with the best correlation for progression (p0.0005) was the cup:disc area ratio. The parameter with the largest area under the receiver operating characteristics curve (0.726) was the vertical cup:disc ratio. The linear discriminant function with the best correlation with progression was [(12.241xcup:disc area ratio)+(3.540xmean cup depth)-(2.146xhorizontal cup:disc ratio)+(27.486xaverage variability)]. An optimised change in the linear discriminant function value was 0.34 with a 65% sensitivity and a 69% specificity for progression.Despite good image quality, the change in the stereometric ONH parameters did not have a high sensitivity and specificity for progression detected with photographs. This indicates that the evaluation of glaucomatous progression in the ONH should not rely solely on the stereometric parameters of the HRT.