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To evaluate the role of intraocular pressure (IOP) fluctuations and other factors on conversion of ocular hypertension to open-angle glaucoma (OAG) within a retrospective, longitudinal cohort study. The study population included patients with ocular hypertension defined by IOP > 21 mmHg with normal appearing optic discs and no visual field defect. IOP fluctuation, mean and maximum were examined in 61 eyes over a follow-up period of 36 months (standard deviation (SD) 24). All patients underwent at least two 48-h IOP profiles including night-time IOP measurements in the supine position, visual field examinations, Heidelberg retina tomograph analyses (HRT) and optic disc photographs. Regression analyses were performed to demonstrate the impact of IOP parameters, myopia, sex, cup/disc ratio and visual field results on conversion to glaucoma. While IOP fluctuation and mean did not impact conversion, myopia proved to be a risk factor (HR 14.4; 95% CI: [3.9–53.0]; p ≤ 0.001). Over an average of three years, 6/61 converted to OAG. The study yielded a mean long-term IOP over all available pressure profiles of 18.1 mmHg (SD 3.2) and an IOP fluctuation of 1.9 mmHg (SD 1.1) within a mostly treated cohort. Conversion-free five-year rate was 59.8%. The amount of fluctuation we measured in our study sample did not result in the development of glaucoma in treated ocular hypertension patients. Myopic subjects with ocular hypertension are at a higher risk for glaucoma conversion than non-myopic ocular hypertensive subjects are.

Summary Background The differentiation between Gaucher disease type 3 (GD3) and type 1 is challenging because pathognomonic neurologic symptoms may be subtle and develop at late stages. The ophthalmologist plays a crucial role in identifying the typical impairment of horizontal saccadic eye movements, followed by vertical ones. Little is known about further ocular involvement. The aim of this monocentric cohort study is to comprehensively describe the ophthalmological features of Gaucher disease type 3. We suggest recommendations for a set of useful ophthalmologic investigations for diagnosis and follow up and for saccadometry parameters enabling a correlation to disease severity. Methods Sixteen patients with biochemically and genetically diagnosed GD3 completed ophthalmologic examination including optical coherence tomography (OCT), clinical oculomotor assessment and saccadometry by infrared based video-oculography. Saccadic peak velocity, gain and latency were compared to 100 healthy controls, using parametric tests. Correlations between saccadic assessment and clinical parameters were calculated. Results Peripapillary subretinal drusen-like deposits with retinal atrophy (2/16), preretinal opacities of the vitreous (4/16) and increased retinal vessel tortuosity (3/16) were found. Oculomotor pathology with clinically slowed saccades was more frequent horizontally (15/16) than vertically (12/16). Saccadometry revealed slowed peak velocity compared to 100 controls (most evident horizontally and downwards). Saccades were delayed and hypometric. Best correlating with SARA (scale for the assessment and rating of ataxia), disease duration, mSST (modified Severity Scoring Tool) and reduced IQ was peak velocity (both up- and downwards). Motility restriction occurred in 8/16 patients affecting horizontal eye movements, while vertical motility restriction was seen less frequently. Impaired abduction presented with esophoria or esotropia, the latter in combination with reduced stereopsis. Conclusions Vitreoretinal lesions may occur in 25% of Gaucher type 3 patients, while we additionally observed subretinal lesions with retinal atrophy in advanced disease stages. Vertical saccadic peak velocity seems the most promising “biomarker” for neuropathic manifestation for future longitudinal studies, as it correlates best with other neurologic symptoms. Apart from the well documented abduction deficit in Gaucher type 3 we were able to demonstrate motility impairment in all directions of gaze.

AimsTo determine the prevalence of myopic maculopathy in the general population in Germany and to analyse potential associations with ocular and systemic factors.DesignThe Gutenberg Health Study is a population-based study, including 15 010 participants aged 35–74 years.MethodsMyopic maculopathy was graded in phakic eyes with spherical equivalent ≤−6 D by assessing fundus photographs according to a recent international photographic classification system (META-PM). 801 eyes of 519 participants (mean age 51.0±0.77 years) met the conditions and had gradable fundus photographs. Age-specific prevalence estimates were computed. Multivariable logistic regression analysis was used to assess associated factors with myopic maculopathy.ResultsMyopic maculopathy was present in 10.3% (95% CI 7.9 to 13.3) study participants. The prevalence was 8.6% (95% CI 6.1% to 11.9%) in the 397 right eyes and 8.7% (95% CI 6.2% to 12.0%) in the 404 left eyes. The most common type of pathology was diffuse atrophy (8.1%), followed by patchy atrophy (1.3%) and macular atrophy (0.5%); plus lesions were present in 3% (right eyes). Age (OR 1.07 per year, 95% CI 1.03 to 1.11, pConclusionsThe prevalence of myopic maculopathy in the German population was 0.5%, and 10% in high myopic participants, aged 35–74 years. These population-based data are the first in Europe. Myopic maculopathy was related to severity of myopic refractive error and age.

Purpose: To evaluate the roles of known myopia-associated genetic variants for development of myopic macular degeneration (MMD) in individuals with high myopia (HM), using case-control studies from the Consortium of Refractive Error and Myopia (CREAM). Methods: A candidate gene approach tested 50 myopia-associated loci for association with HM and MMD, using meta-analyses of case-control studies comprising subjects of European and Asian ancestry aged 30 to 80 years from 10 studies. Fifty loci with the strongest associations with myopia were chosen from a previous published GWAS study. Highly myopic (spherical equivalent [SE] ≤ -5.0 diopters [D]) cases with MMD (N = 348), and two sets of controls were enrolled: (1) the first set included 16, 275 emmetropes (SE ≤ -0.5 D); and (2) second set included 898 highly myopic subjects (SE ≤ -5.0 D) without MMD. MMD was classified based on the International photographic classification for pathologic myopia (META-PM). Results: In the first analysis, comprising highly myopic cases with MMD (N = 348) versus emmetropic controls without MMD (N = 16, 275), two SNPs were significantly associated with high myopia in adults with HM and MMD: (1) rs10824518 (P = 6.20E-07) in KCNMA1, which is highly expressed in human retinal and scleral tissues; and (2) rs524952 (P = 2.32E-16) near GJD2. In the second analysis, comprising highly myopic cases with MMD (N = 348) versus highly myopic controls without MMD (N = 898), none of the SNPs studied reached Bonferroni-corrected significance. Conclusions: Of the 50 myopia-associated loci, we did not find any variant specifically associated with MMD, but the KCNMA1 and GJD2 loci were significantly associated with HM in highly myopic subjects with MMD, compared to emmetropes., Correction--10 Oct 2019: Wong YL, Hysi P, Cheung G, Tedja M, Hoang QV, et al. (2019) Correction: Genetic variants linked to myopic macular degeneration in persons with high myopia: CREAM Consortium. PLOS ONE 14(10): e0223942. https://doi.org/10.1371/journal.pone.0223942

Objective PDZD7 was identified in 2009 in a family with apparent nonsyndromic sensorineural hearing loss. However, subsequent clinical reports have associated PDZD7 with digenic Usher syndrome, the most common cause of deaf-blindness, or as a modifier of retinal disease. No further reports have validated this gene for nonsyndromic hearing loss, intuitively calling correct genotype-phenotype association into question. This report describes a validating second case for biallelic mutations in PDZD7 causing nonsyndromic mild to severe sensorineural hearing loss. It also provides detailed audiometric and ophthalmologic data excluding Usher syndrome in both the present proband (proband 1) and the first proband described in 2009 (proband 2). Design Proband 1 was sequenced using a custom-designed next generation sequencing panel consisting of 151 deafness genes. Bioinformatics analysis and filtering disclosed two PDZD7 sequence variants (c.1648C>T, p.Q550* and c.2107del, p.S703Vfs*20). Segregation testing followed in the family. For both probands, audiograms were collected and analyzed for progressive hearing loss and detailed ophthalmic evaluations were performed including electroretinography. Results Proband 1 demonstrated a prelingual, nonsyndromic, sensorineural hearing loss that progressed in the higher frequencies between 4 and 9 years old. PDZD7 segregation analysis confirmed biallelic inheritance (compound heterozygosity). Mutation analysis determined the c.1648C>T mutation as novel and reported the c.2107del deletion as rs397516633 with a calculated minor allele frequency of 0.000018. Clinical evaluation spanning well over a decade in proband 2 disclosed bilateral, nonprogressive hearing loss. Both probands showed healthy retinas, excluding Usher syndrome-like changes in the eye. Conclusions PDZD7 is confirmed as a bona fide autosomal recessive nonsyndromic hearing loss gene. In both probands, there was no evidence of impaired vision or ophthalmic pathology. As the current understanding of PDZD7 mutations bridge Mendelian and complex phenotypes, the authors recommend careful variant interpretation, since PDZD7 is one of many genes associated with both Usher syndrome and autosomal recessive nonsyndromic hearing loss. Additional reports are required for understanding the complete phenotypic spectrum of this gene, including the possibility of high-frequency progression, as well as noise-induced hearing loss susceptibility in adult carriers. This report rules out all forms of Usher syndrome with an onset before 12 and 15 years old in probands 1 and 2, respectively. However, due to the young ages of the probands, this report is uninformative regarding older patients.

Background: Discrepancies in ionised calcium concentrations between results from several point-of-care devices derived from intensive care unit (ICU) patients were postulated to be caused by perchlorate, a thyroid blocking agent. The deviations were serious concerning the diagnosis of hyper- or hypocalcaemia and administration of calcium infusions. Methods: The problem was studied from three perspectives. First: quantification of ionised calcium in heparinised blood samples spiked with sodium perchlorate from healthy volunteers measured using five blood gas analysers (BGAs from IL, Radiometer, Roche and Siemens). Second: verification of clinical concentrations of perchlorate in blood samples after routine use for blood gas analysis from ICU patients. Third: retrospective analysis of data stored from patients during their stay in general ICU of the Departments of Anesthesio-logy and General Surgery by a patient data management system. Results: Category 1: three of the point-of-care testing devices measure clinically relevant falsely low ionised calcium concentrations when exposed to concentrations perchlorate >0.1 mmol/L. Two were not able to identify hypercalcaemia of up to 4 mmol/L ionised calcium when specific perchlorate concentrations are exceeded. Category 2: measured clinical concentrations of perchlorate ranged between the lower limit of quantification [LOQ=0.03 mmol/L and 2.75 mmol/L (median=0.29 mmol/L; mean=0.585 mmol/L)]. A concentration above 0.1 mmol/L perchlorate was found in 74.3% of all samples that tested positive. Category 3: between February 2006 and July 2009, 42 patients per year (2.2%) received sodium perchlorate with a median length of treatment of 25 days. Conclusions: Perchlorate causes clinically relevant lowering of measured ionised calcium in BGAs from two providers at concentrations obtained in samples from ICU patients (affecting about 1.1% of all ICU patients).

BACKGROUND To create awareness for mismeasurements of ion-selective electrodes caused by patients' medications and to prevent severe consequences in an intensive care therapy. CASE PRESENTATION A 73-year-old woman presented with severe carbimazol-induced toxic epidermal necrolysis. After replacement of carbimazol by sodiumperchlorate, we detected a huge discrepancy in the measurement of ionised calcium by two different Point-of-Care (POCT) systems. While Siemens Rapidlab 865 showed a severe hypocalcemia at all times, the Radiometer 600 system first presented a severe hypercalcemia and, in the course of the following days, also a hypocalcemia but with significantly (p < 10 to the -45) higher values than the Rapidlab system. Furthermore, the POCT systems detected a pseudohypocalcemia at times where we think there was a normo- or even hypercalcemia which led to incorrect therapy with excessive substitution of ionised calcium. CONCLUSIONS The substance sodiumperchlorate, which is well established in Europe for hyperthyreosis therapy, caused malfunctions of analyses of ionised calcium by POCT systems.

Fast and reliable glycemic control is of tremendous importance in intensive care units. Point-of-care devices used in professional care have to be precise and of low variability, and their connectivity has to outrange the abilities of home-care equivalents. In particular, the meter's efficiency should be tested not only with spiked blood samples from healthy donors but also with blood from intensive care unit patients because of their special matrix conditions as low hematocrit, oxygen pressure variability, or medication.Four types of network-ready glucose meters were tested. Data, obtained from native or maltose/xylose-spiked intensive care patients' blood, were compared (oxygen, hematocrit, glucose, and maltose and xylose dependencies) with those from a YSI 2300 STAT Plus™ glucose and lactate analyzer (YSI Life Sciences, Yellow Springs, OH). According to ISO 15197 (2003) acceptance of glucose meter results was determined. Quality control results were investigated considering a new calculation type in German guidelines.Three of the meters fulfill the overall acceptance criterions. Two of the meters achieved accuracies above 93% in all oxygen, hematocrit, and glucose subgroups. Maltose generates deviations leading to accuracies from 71.1% to 100%, and xylose causes accuracies of 33.3% to 100%.State of the art for manufacturing small network point-of-care testing glucose meters has reached a new level of precision, but the devices still have to be handled with care, and in particular the staff of an intensive care unit still needs knowledge about possible interferences.