Ocular geometry in adults born extremely, very and moderately preterm with and without retinopathy of prematurity: results from the Gutenberg Prematurity Eye Study

Background/aims: To evaluate whether anterior segment anatomy and axial length are associated with prematurity and perinatal factors in adults. Methods: The Gutenberg Prematurity Eye Study examined adults born preterm and term aged 18–52 years. All participants underwent a prospective ophthalmic examination (optical biometry via a LenStar 900, Haag-Streit) in Germany. The associations between gestational age (GA), birth weight (BW) and BW percentile, retinopathy of prematurity (ROP) occurrence, ROP treatment and other perinatal factors with the main outcome measures were evaluated by univariate and multivariable linear regression analyses. Main outcome measures were corneal radius, white-to-white distance, anterior chamber depth, lens thickness and axial length. Results: The study involved 861 eyes of 438 preterm and full-term individuals (aged 28.6±8.7 years, 245 females,). After adjustment for age and gender, a steeper corneal radius was associated with lower GA (B=0.02; p<0.001) and a lower BW percentile (B=0.003; p<0.001). A smaller white-to-white distance was linked to lower GA (B=0.02; p<0.001), a lower BW percentile (B=0.004; p<0.001) and postnatal ROP occurrence (B=−0.26; p<0.001). Decreased axial length was associated with lower GA at birth (B=0.05; p=0.002) and pre-eclampsia (B=−0.34; p=0.015). ROP-treated eyes had a shallower anterior chamber depth (B=−0.63; p=0.001) and increased lens thickness (B=0.64, p<0.001). Conclusion: Our analyses in adults demonstrate that the corneal morphology is influenced by GA and BW percentile, while the anterior chamber depth and lens thickness are affected by ROP treatment, namely laser therapy and cryotherapy. The present study highlights that perinatal factors lead to lifelong sequelae of ocular shape

Visual acuity, amblyopia, and vision-related quality of life in preterm adults with and without ROP : results from the Gutenberg prematurity eye study

Objectives This study investigated the effects of prematurity and ROP on visual acuity and VRQoL in adults (18–52 years). Methods The Gutenberg Prematurity Eye Study is a retrospective cohort study with a prospective ophthalmologic examination. Preterm and full-term participants at an age from 18 to 52 years were included. Distant corrected visual acuity (DCVA) and VRQoL were assessed in participants (892 eyes of 450 individuals aged 28.6 ± 8.6 years, 251 females) grouped into full-term controls (gestational age [GA] at birth ≥37 weeks), preterm participants without ROP and GA 33–36 weeks (group 2), GA 29–32 weeks (group 3), GA ≤ 28 weeks (group 4), non-treated ROP (group 5) and treated ROP (group 6). Main outcome measures were distant corrected visual acuity (DCVA), VRQoL and prevalence of amblyopia. Results The DCVA of the better eye correlated (p < 0.001) with GA, birth weight, ROP, ROP treatment, and perinatal adverse events and was poorer in both ROP groups. Visual acuity of <20/200 in the better eye was observed in two participants (4.2%) in the ROP group and one person (6.7%) in the treated ROP group. The prevalence of amblyopia increased in the ROP groups. Compared to full-term controls, visual functioning VRQoL scores were lower in preterm individuals independent of ROP while socioemotional VRQoL scores were only lower in the treated ROP group. Conclusion Participants with postnatal ROP and its treatment showed decreased visual acuity and VRQol in adulthood, with amblyopia occurring more frequently in more preterm participants with ROP

A singleplex IgE test to a mixture of molecules from multiple airborne allergen sources: Innovating in vitro screening of respiratory allergies

Background In vitro immunoglobulin E (IgE) tests can be better standardized if based on molecules rather than extracts. However, singleplex screening tests for respiratory or food allergies are still based on extracts only. Target To validate a novel singleplex IgE screening test for respiratory allergies, based on a mix of major allergenic molecules Der p 1, Der p 2, Fel d 1, Can f 1, Can f 2, Can f 3, Can f 5, Bet v 1, Phl p 1, and Art v 1 (Molecular SX01, NOVEOS, HYCOR, USA), and requiring only four microliters (μl) of serum. Methods We examined six subsets of sera from participants of the German Multicenter Allergy Study (MAS) birth cohort enrolling 1314 newborns during 1990: (1) monosensitized (n = 58); (2) polysensitized (n = 24); (3) nonsensitized, with total IgE levels above (n = 24) or (4) below (n = 24) 300 kU/L; (5) sensitized to milk and/or egg but not to airborne allergens (n = 24); and (6) sera of children aged ≤5 years at their earliest IgE monosensitization to airborne allergens (n = 41). Sera were analyzed with the novel molecular SX01 test (NOVEOS) and with three categories of comparators: ImmunoCAP Phadiatop SX01, extracts, and molecules of D. pteronyssinus, cat, dog, grass, and birch. Sensitivity, specificity, positive and negative predictive values were calculated. Quantitative interrelationships were determined using Spearman's rank-order correlation coefficient and Bland–Altmann plots. Results The molecular SX01 test predicted the outcome of IgE tests based on molecules, extracts, or Phadiatop in 188 (96.4%), 171 (87.7%), and 171 (87.7%) of the 195 sera, respectively. Accordingly, sensitivity was 93.5%, 89.0%, and 82.4%, whereas specificity was 100%, 97.6%, and 96.1% when compared with molecular, extract, and Phadiatop tests, respectively. Inconsistent outcomes were largely confined to sera with IgE-Ab levels around the cutoff value of 0.35 kU/L, except for 5/195 (2.5%) sera, containing high levels of IgE to Phl p 5 and/or Alt a 1 only. IgE levels measured by the molecular SX01 test and with IgE tests to molecules, extracts, and Phadiatop were highly correlated (rho 0.90; p < .001), (rho 0.87, p < .001), (rho 0.84, p < .001), respectively. The novel molecular SX01 test detected IgE-Ab in 27/28 (sensitivity 96.4%) of the sera of preschool children at their earliest IgE sensitization to the same molecules. Discussion Our study validates the prototype of a novel category of IgE test, based on molecular mixes. The test's rather good precision and accuracy in early screening IgE sensitization to airborne allergens in German children may be further improved by adding a few other molecules, such as Phl p 5 and Alt a 1

A lower birth weight percentile is associated with central corneal thickness thinning : results from the Gutenberg Prematurity Eye Study (GPES)

Purpose: Prematurity, prenatal growth restriction, and retinopathy of prematurity (ROP) are associated with altered ocular geometry, such as a steeper corneal shape in childhood, but it is unclear whether perinatal history affects corneal thickness development, so this study investigated whether corneal thickness in adulthood is affected by perinatal history. Marterials and Methods: The Gutenberg Prematurity Eye Study (GPES) is a retrospective cohort study with a prospective ophthalmologic examination in Germany. The corneal thickness was measured by Scheimpflug imaging (Pentacam HR, Oculus Optikgeräte GmbH, Wetzlar, Germany), and the relationship between perinatal parameters respective birth weight percentile and corneal thickness at different locations was assessed using uni- and multivariable linear regression models. Covariates included age, sex, mean corneal radius, white-to-white distance, gestational age, birth weight percentile, ROP occurrence, and treatment. The main outcome measures were corneal thickness at the apex, the pupil center, and the corneal periphery. Results: The corneal thickness was measured in 390 participants (754 eyes, mean age 29.7+/-8.7 years, 224 females). In multivariable analyses, a lower birth weight percentile was associated with a lower corneal thickness at the apex (B = 0.20, p = 0.003) and the pupil (B = 0.19, p = 0.007). These effects diminished towards the corneal periphery and were not observed beyond the 4-mm diameter circle around the thinnest corneal position. Neither gestational age, ROP occurrence, or ROP treatment affected the corneal thickness. Conclusion: A lower birth weight percentile in subjects born preterm as a proxy for restricted fetal growth is associated with corneal thickness thinning in adults aged 18 to 52 years, indicating that corneal thickness development, particularly in the corneal center, may originate in the fetal stage

The role of preterm birth, retinopathy of prematurity and perinatal factors on corneal aberrations in adulthood : results from the Gutenberg prematurity eye study

Introduction Prematurity and retinopathy of prematurity (ROP) are associated with altered corneal shape and reduced visual acuity in childhood, but their long-term effects on corneal shape in later life are still unclear. This study evaluated whether prematurity and related perinatal factors are associated with corneal aberrations in adulthood. Methods The Gutenberg Prematurity Eye Study (GPES) is a cohort study using Scheimpflug imaging of the cornea. Associations were assessed between corneal Zernike aberrations and gestational age (GA), birth weight (BW), BW percentile, ROP occurrence, ROP treatment and other perinatal factors using univariate and multivariable linear regression analyses. Results This study involved 444 eyes of 256 individuals born preterm (aged 28.1 ± 8.4 years, 146 females) and 231 eyes of 132 individuals born full-term (aged 29.8 ± 8.9 years, 77 females). Multivariable analyses revealed an association between corneal higher-order aberrations and lower birth weight percentile (B = −0.001, p < 0.001) as well as ROP treatment (B = 0.120, p = 0.03). Corneal lower-order aberrations were also associated with lower birth weight percentile (B = −0.004; p = 0.001) and ROP treatment (B = 0.838, p = 0.01) but not with ROP occurrence. Increased corneal aberrations were correlated with lower visual acuity and the spherical equivalent refractive error. Conclusions Perinatal factors, particularly low birth weight percentile and ROP treatment lead to a more irregular corneal shape in adulthood, thereby reducing optical image quality and potentially contributing to reduced visual acuity and altered refractive error

Arzneimittel für neuartige Therapien – Perspektiven, Chancen, Herausforderungen

Zusammenfassung Arzneimittel für neuartige Therapien (ATMP) wie somatische Gentherapie und Zelltherapie besitzen ein hohes therapeutisches Potenzial für Krankheiten, die sehr früh im Leben beginnen, und die bisher nicht behandelbar waren. Sie werden oft in einem sehr frühen Entwicklungsstadium zugelassen, wenn an wenigen Betroffenen die Wirksamkeit gezeigt wurde und sich ein bisher nie dagewesener Therapieerfolg auftut, vor allem, wenn die Therapie vor Eintritt von Organschäden greift. Dadurch ergeben sich für Pädiater neue arzneimittelrechtliche und ethische Fragen. Um die neuen Behandlungsmöglichkeiten adäquat einzusetzen, muss die Diagnose früher als bisher gestellt werden, oder neue Screeningmethoden müssen zur Verfügung stehen. Denkbar ist, dass das Neugeborenenscreening in zeitkritische Krankheiten in den ersten 72 h nach Geburt und ein genetisches Screening (z. B. in der 4. bis 5. Lebenswoche) aufgeteilt wird. ATMP sind bei ihrer Zulassung noch nicht in ausreichender Anzahl angewendet worden, sodass die notwendigen Erkenntnisse für Wirksamkeit und Sicherheit noch nicht vorliegen (Nutzen-Risiko-Verhältnis). Deswegen werden sie unter strengen Auflagen in spezialisierten Behandlungszentren nach Qualitätskriterien eingesetzt, die der Gemeinsame Bundesausschuss (G-BA) nach Beratung mit den Fachgesellschaften festlegt. Der Aufwand der Therapie und der Dokumentation des Verlaufes in Registern ist erheblich und muss entsprechend vergütet werden. Der Wert eines ATMP wird erst mit seiner breiteren Anwendung nach der Zulassung klar, ähnlich wie die Sicherheit eines Arzneimittels nicht mit der Zulassung vollumfänglich bekannt ist. Für die Pädiatrie ergeben sich neue Herausforderungen und Chancen

Beschluss und Wissenschaftliche Begründung der Ständigen Impfkommission (STIKO) für die Aktualisierung der Influenza-Impfempfehlung für Personen im Alter von ≥ 60 Jahren

Die STIKO empfiehlt allen Personen im Alter von ≥60 Jahren im Herbst eine jährliche Impfung gegen die saisonale Influenza mit einem inaktivierten, quadrivalenten Influenza-Hochdosis-Impfstoff mit aktueller von der WHO empfohlener Antigenkombination. Solange Hochdosis-Impfstoffe für die Altersgruppe 60-64 Jahre nicht zugelassen sind, werden für die Influenza-Impfung von Personen in diesem Alter weiterhin inaktivierte, quadrivalente Influenza-Impfstoffe (unabhängig vom Impfstofftyp) empfohlen. Eine Empfehlung für die Anwendung eines Influenza-Hochdosis-Impfstoffs ist in gleichem Maße bei der Impfempfehlung für Reisende zu berücksichtigen. Die Veröffentlichung dieser Empfehlung zu diesem Zeitpunkt, ohne Berücksichtigung der aktuellen Verfügbarkeit von Influenza-Hochdosis-Impfstoffen, soll gewährleisten, dass der entsprechende Impfstoffbedarf bei der Planung, Produktion und Beschaffung von Influenza-Impfstoffen ab der Saison 2021/2022 berücksichtigt werden kann

Dry Eye Parameters and Lid Geometry in Adults Born Extremely, Very, and Moderately Preterm with and without ROP: Results from the Gutenberg Prematurity Eye Study

Background/Aims: This study aimed to analyze the effects of perinatal history on tear film properties and lid geometry in adults born preterm. Methods: The Gutenberg Prematurity Eye Study (GPES) is a German prospective examination of adults born preterm and term aged 18 to 52 years with Keratograph® 5M and Schirmer test I. Main outcome measures were first non-invasive tear film break-up time (F-NITBUT), bulbar redness (BR), Schirmer test, and nasal palpebral angle measurement. The associations with gestational age (GA), birth weight (BW), and BW percentile, retinopathy of prematurity (ROP), ROP treatment, and other perinatal factors were evaluated using regression analyses. Results: 489 eyes of 255 preterm and 277 eyes of 139 full-term individuals (aged 28.6 +/− 8.8 years, 220 females) were included. Of these, 33 participants (56 eyes) had a history of spontaneously regressed ROP and 9 participants (16 eyes) had a history of ROP treatment. After adjustment for age and sex, lower F-NITBUT (<20 s) was associated with ROP treatment (OR = 4.42; p = 0.025). Lower GA correlated with increased bulbar redness (B = −0.02; p = 0.011) and increased length of wetting in the Schirmer test (B = −0.69; p = 0.003). Furthermore, low GA was associated with narrowing of the nasal palpebral angle (B = 0.22; p = 0.011) adjusted for age and sex, but not when considering ROP in the multivariable model. Conclusion: Our analyses indicate that perinatal history affects ocular surface properties, tear production and lid geometry in adults born term and preterm. This might indicate that affected persons have a predisposition to diseases of the corneal surface such as the dry eye disease

Der p 23‐specific IgE response throughout childhood and its association with allergic disease: A birth cohort study

Background The Dermatophagoides pteronyssinus molecule Der p 23 is a major allergen whose clinical relevance has been shown in cross-sectional studies. We longitudinally analysed the trajectory of Der p 23-specific IgE antibody (sIgE) levels throughout childhood and youth, their early-life determinants and their clinical relevance for allergic rhinitis and asthma. Methods We obtained sera and clinical data of 191 participants of the German Multicentre Allergy Study, a prospective birth cohort. Serum samples from birth to 20 years of age with sIgE reactivity to Der p 23 in a customised semiquantitative microarray were newly analysed with a singleplex quantitative assay. Early mite exposure was assessed by measuring the average content of Der p 1 in house dust at 6 and 18 months. Results Der p 23-sIgE levels were detected at least once in 97/191 participants (51%). Prevalence of Der p 23 sensitisation and mean sIgE levels increased until age 10 years, plateaued until age 13 years and were lowest at age 20 years. Asthma, allergic rhinitis (AR) and atopic dermatitis (AD) were more prevalent in Der p 23-sensitised children, including those with monomolecular but persistent sensitisation (11/97, 11%). A higher exposure to mites in infancy and occurrence of AD before 5 years of age preceded the onset of Der p 23 sensitisation, which in turn preceded a higher incidence of asthma. Conclusions Der p 23 sensitisation peaks in late childhood and then decreases. It is preceded by early mite exposure and AD. Asthma and AR can occur in patients persistently sensitised to Der p 23 as the only mite allergen, suggesting the inclusion of molecular testing of Der p 23-sIgE for subjects with clinical suspicion of HDM allergy but without sIgE to other major D.pt. allergens