Objective The role of placental inflammation in neonatal morbidities is underestimated due to lack of placental examination. This meta-analysis aims to assess the association between histological... Show moreObjective The role of placental inflammation in neonatal morbidities is underestimated due to lack of placental examination. This meta-analysis aims to assess the association between histological chorioamnionitis (HCA) with and without funisitis (FUN) and risk of retinopathy of prematurity (ROP).Study Design Forty-five studies reporting (unadjusted) data on HCA without FUN and HCA with FUN in neonates with ROP were included. Primary outcomes were any stage ROP and severe ROP. Potential confounders explored were gestational age (GA) at birth, birthweight, maternal steroid use, necrotizing enterocolitis, sepsis (suspected/proven) and mechanical ventilation duration.Results Neonates with HCA had increased risk for any stage ROP (odds ratio [OR] 1.8; 95% confidence interval [CI] 1.3-2.4) and severe ROP (OR 1.5; 95% CI 1.2-1.8) compared with neonates without HCA. The rates of any stage ROP (OR 1.8; 95% CI 1.4-2.2) and severe ROP (OR 1.4; 95% CI 1.1-1.6) were higher in neonates with FUN compared with neonates without FUN. Multivariate meta-regression analysis suggests that lower GA increases the effect size between FUN and severe ROP.Conclusion This meta-analysis confirms that presence of HCA and FUN are risk factors for any stage ROP and severe ROP. Structured histological placental examination of HCA and FUN may be a tool to further refine the ROP risk profile. Show less
Emrani, S. el; Meeren, L.E. van der; Lopriore, E.; Schalij-Delfos, N.E. 2023
Purpose: To assess the longitudinal vision-related quality of life among patients with CRB1-associated inherited retinal dystrophies.Methods: A longitudinal questionnaire study included 22 patients... Show morePurpose: To assess the longitudinal vision-related quality of life among patients with CRB1-associated inherited retinal dystrophies.Methods: A longitudinal questionnaire study included 22 patients with pathogenic CRB1 variants. The National Eye Institute Visual Function Questionnaire (39 items, NEI VFQ-39) was applied at baseline, two-year follow-up, and 4-year follow-up. Classical test theory was performed to obtain subdomain scores and in particular 'near activities' and 'total composite' scores. The Rasch analysis based on previous calibrations of the NEI VFQ-25 was applied to create visual functioning and socio-emotional subscales.Results: In total, 22 patients with pathogenic CRB1 variants were included, with a median age of 25.0 years (IQR: 13-31 years) at baseline and mean followup of 4.0 +/- 0.3 years. A significant decline at 4 years was observed for 'near activities' (51.0 +/- 23.8 vs 35.4 +/- 14.7, p = 0.004) and 'total composite' (63.0 +/- 13.1 vs 52.0 +/- 12.1, p = 0.001) subdomain scores. For the Rasch-scaled scores, the 'visual functioning' scale significantly decreased after 4 years (- 0.89 logits; p = 0.012), but not at 4-year follow-up (+0.01 logits; p = 0.975). The 'socio- emotional' scale also showed a significant decline after 2 years (-0.78 logits, p = 0.033) and 4 years (- 0.83 logits, p = 0.021).Conclusion: In the absence of an intervention, a decline in vision-related quality of life is present in patients with pathogenic CRB1 variants at 4-year follow-up. Patient-reported outcome measures should be included in future clinical trials, as they can be a potential indicator of disease progression and treatment efficacy. Show less
To compare EEG-patterns after instillation of cyclopentolate versus placebo eye drops. Prospective, randomized, placebo-controlled, and observational pilot study is presented. Ophthalmology... Show moreTo compare EEG-patterns after instillation of cyclopentolate versus placebo eye drops. Prospective, randomized, placebo-controlled, and observational pilot study is presented. Ophthalmology outpatient clinic Dutch metropolitan hospital. Healthy 6- to 15-year-old volunteers with normal or low BMI requiring a cycloplegic refraction/retinoscopy. Randomized; 1 visit 2 drops cyclopentolate-1% and 1 visit 2 drops placebo (saline-0.9%). Single-blind: conducting researcher. Double blind: subjects, parents, clinical-neurophysiology staff, neurologist, and statistician. A 10-min baseline EEG-recording, drop-application, and follow-up to at least 45 min. Primary outcome: Detection of CNS changes, i.e. EEG-pattern changes, following two drops of cyclopentolate-1%. Secondary outcome: Determination of the extent of these pattern changes. Thirty-six cyclopentolate-1% saline-0.9% EEG registrations were made in 33 subjects; 18 males and 15 females. Three subjects were tested twice (interval 7 months). Nine out of fourteen (64%) of the 11- to 15-year-old children reported impaired memory, attention, alertness, as well as mind wandering following cyclopentolate. Drowsiness and sleep were seen in EEG-recordings of 11 subjects (33%) following cyclopentolate. We observed no drowsiness nor sleep during placebo recordings. The mean time to drowsiness was 23 min. Nine subjects arrived in stage-3 sleep but none arrived in REM-sleep. In subjects without sleep (N=24), significant changes compared to placebo-EEG were present for many leads and parameters. The main findings during awake eye-open recording were as follows: 1) a significant increase of temporal Beta-1,2 and 3-power, and 2) a significant decrease in: a) the parietal and occipital Alpha-2-power, b) the frontal Delta-1-power, c) the frontal total power, and d) the occipital and parietal activation synchrony index. The former finding reflects cyclopentolate uptake in the CNS, and the latter findings provide evidence for CNS suppression. Cyclopentolate-1% eye drops can affect the CNS and may cause altered consciousness, drowsiness, and sleep with concomitant EEG results in both young children and children in puberty. There is evidence that cyclopentolate has the potency to act as a short acting CNS depressant. Nevertheless, however, cyclopentolate-1% can safely be used in children and young adolescents. Show less
BackgroundResearch in singletons identified fetal growth restriction (FGR) as a risk factor for retinopathy of prematurity (ROP), but is generally subject to confounding by genetic, obstetric, and... Show moreBackgroundResearch in singletons identified fetal growth restriction (FGR) as a risk factor for retinopathy of prematurity (ROP), but is generally subject to confounding by genetic, obstetric, and maternal factors. We investigated the effect of FGR on ROP in growth-discordant identical twins, thereby controlling for confounding factors.MethodsAll data of monochorionic (MC) twin pairs with a birth weight discordance >= 20% born in our center between 2010 and 2021 were retrospectively reviewed for the presence of ROP. Potential risk factors for ROP were analyzed. Outcomes were compared between the smaller and larger twin.ResultsWe included 88 MC twin pairs with growth discordance. In 34% (30/88), both neonates were at risk of ROP. Prevalence of ROP was higher among the smaller twin compared to the larger twin, 30% (9/30) versus 13% (4/30), respectively (OR 2.8, 95% CI: 1.2-6.6). The smaller twin had a longer duration of mechanical ventilation (8 (1-20) versus 2 (1-4) days) and received their first red blood cell transfusion at an earlier postmenstrual age (29.6 (28.1-31.6) versus 30.4 (29.7-32.6) weeks).ConclusionsIn this identical twin model, FGR is associated with almost tripled odds of ROP development, suggesting that both unfavorable antenatal growth conditions and adverse neonatal outcomes affect postnatal retinal vascular proliferation.ImpactFetal growth restriction in growth-discordant identical twins is associated with almost tripled odds of developing retinopathy of prematurity in the smaller twin.Since these twins do not only differ in birth weight but also duration of mechanical ventilation and timing of the first red blood cell transfusion, both unfavorable antenatal growth conditions and adverse neonatal outcomes can affect postnatal retinal vascular proliferation.More attention for preventing retinopathy of prematurity is needed in those with fetal growth restriction who received prolonged duration of mechanical ventilation, oxygen supplementation, or a first red blood cell transfusion Show less
Aim: Determine incidence of visual impairment due to retinopathy of prematurity (ROP) and concomitant dis-abilities between 2009 and 2018 in the Netherlands and compare data to four former similar... Show moreAim: Determine incidence of visual impairment due to retinopathy of prematurity (ROP) and concomitant dis-abilities between 2009 and 2018 in the Netherlands and compare data to four former similar studies. Secondly, monitor if infants were missed for ROP-screening since the adoption of stricter, risk factor guided criteria (2013).Methods: Retrospective inventory on anonymous data of infants diagnosed with ROP from Dutch visual impairment-institutes. Data including: best corrected visual acuity, ROP-treatment and concomitant disabilities: bronchopulmonary dysplasia, behavioral abnormalities, epilepsy, hearing deficit, developmental delay, cerebral palsy and cerebral visual impairment. During the study period, lower age limit for neonatal life support (2010) and higher oxygen saturation targets (2014) were implemented.Results: Records of 53 infants were analyzed. Visual impairment incidence due to ROP was 2.02 per 100.000 live births (2000-2009: 1.84, p = 0.643). Compared to earlier periods (1975-2000), a significant decrease was observed. The incidence of concomitant disabilities remained stable. Mean gestational age (GA) continued to decrease to 26.6 & PLUSMN; 1.9 weeks (2000-2009: 27.4 & PLUSMN; 2.0 weeks, p = 0.047). All patients met the screening inclusion criteria.Conclusion: The incidence of visual impairment due to ROP and concomitant disabilities between 2009 and 2018 has not increased, despite lower GA and higher oxygen saturation targets. None of the infants were missed for ROP screening following introduction of more restricted screening inclusion criteria. Show less
Emrani, S. el; Groene, S.G.; Spekman, J.A.; Slaghekke, F.; Meeren, L.E. van der; Schalij-Delfos, N.E.; Lopriore, E. 2023
Introduction: The purpose of this study was to evaluate the within-pair difference in retinopathy of prematurity (ROP) between donors and recipients with twin-to-twin transfusion syndrome (TTTS)... Show moreIntroduction: The purpose of this study was to evaluate the within-pair difference in retinopathy of prematurity (ROP) between donors and recipients with twin-to-twin transfusion syndrome (TTTS) and to identify risk factors for ROP development.Methods: This retrospective cohort study included 147 TTTS twin pairs managed between 2002-2022 and eligible for ROP screening. Primary outcomes were any stage ROP and severe ROP. Secondary outcomes were hemoglobin at birth, red blood cell transfusions, mechanical ventilation days, postnatal steroids and neonatal morbidity.Results: Rates of any stage ROP (23% vs. 14%) and severe ROP (8% vs. 3%) were significantly higher in donors compared to recipients. Donors received a higher number of blood transfusions (1 (+/- 1.9) vs. 0.7 (+/- 1.5)). Five factors were univariately associated with any stage ROP: donor status (OR 1.9; 95% CI 1.3-2.9), lower GA at birth (OR 1.7; 95% CI 1.4-2.1), small for GA (OR 2.1; 95% CI 1.3-3.5), mechanical ventilation days (OR 1.1; 95% CI 1.1-1.2) and blood transfusions in phase 1 (OR 2.3; 95% CI 1.2-4.3). Three factors were independently associated with any stage ROP: donor status (OR 1.8; 95% CI 1.1-2.9), lower GA at birth (OR 1.6; 95% CI 1.2-2.1) and mechanical ventilation days (OR 1.1, 95% CI 1.0-1.1). Donor status was univariately associated with severe ROP (OR 2.3, 95% CI 1.1-5.0). Conclusion: Any stage ROP and severe ROP are detected twice as frequently in donors compared to recipients. Increased awareness for ROP is needed in donors, especially those with lower GA at birth and longer duration of mechanical ventilation. Show less
Nusman, C.M.; Schalij-Delfos, N.E.; Groenwold, R.H.H.; Onland, W. 2022
Strategies to ensure high intraocular oxygen delivery to the developing retina after 32 weeks gestational age, such as higher saturation targets and/or higher hemoglobin levels, are hypothesized to... Show moreStrategies to ensure high intraocular oxygen delivery to the developing retina after 32 weeks gestational age, such as higher saturation targets and/or higher hemoglobin levels, are hypothesized to prevent ophthalmological treatment for retinopathy of prematurity (ROP). This short report summarizes the current evidence of these strategies, and discusses possibilities of future studies. A large sample size would be required and therefore the feasibility of a future randomized controlled trial is questioned. Show less
Trzcionkowska, K.; Schalij-Delfos, N.E.; Akker-van Marle, E.M.E. van den 2022
Purpose: Evaluate possibilities to reduce the number of infants screened for retinopathy of prematurity (ROP) and investigate costs and number of infants detected of current and alternative... Show morePurpose: Evaluate possibilities to reduce the number of infants screened for retinopathy of prematurity (ROP) and investigate costs and number of infants detected of current and alternative screening strategies in the Netherlands. Methods: Prospective population-based study including clinical data from all infants born in 2017 and referred for ROP screening (NEDROP-2 study). Cost and effects of screening strategies were evaluated that differed on the criteria gestational age (GA), birth weight (BW) and presence of one or more specific risk factor(s) (RF): mechanical ventilation, sepsis, necrotizing enterocolitis, postnatal corticoids and/or hypotension treated with inotropic agents. RF obtained from the Dutch perinatal registry (Perined). Results: Of the possible efficient strategies, the annual costs varied from euro137 966 (inclusion of BW < 700, 63 infants eligible for screening, detection of 17/39 treated ROP) to euro492 689 (GA < 30 weeks and BW < 1250 grams, together with infants with GA 30-32 and BW 1250-1500 grams with presence of one more RF, 744 infants eligible for screening, all treated infants detected). Total annual costs of the current Dutch guideline that detects all infants that need treatment for ROP amount to euro552 143). Conclusion: The current Dutch ROP guideline can be improved by implementing new screening inclusion criteria. The most effective strategy detecting all severe and treated infants, reduces the number of screened infants by 24% compared to the current guideline and the overall annual costs by euro59454. Show less
PURPOSE. The purpose of this study was to further expand the mutational spectrum of the Foveal Hypoplasia, Optic Nerve Decussation defect, and Anterior segment abnormalities (FHONDA syndrome), to... Show morePURPOSE. The purpose of this study was to further expand the mutational spectrum of the Foveal Hypoplasia, Optic Nerve Decussation defect, and Anterior segment abnormalities (FHONDA syndrome), to describe the phenotypic spectrum, and to compare it to albinism.SUBJECTS AND METHODS. We retrospectively collected molecular, ophthalmic, and electro-physiological data of 28 patients molecularly confirmed with FHONDA from the Netherlands (9), Israel (13), France (2), and the United States of America (4). We compared the data to that of 133 Dutch patients with the 3 most common types of albinism in the Netherlands: oculocutaneous albinism type 1 (49), type 2 (41), and ocular albinism (43).RESULTS. Patients with FHONDA had a total of 15 different mutations in SLC38A8, of which 6 were novel. Excluding missing data, all patients had moderate to severe visual impairment (median visual acuity [VA] = 0.7 logMAR, interquartile range [IQR] = 0.60.8), nystagmus (28/28), and grade 4 foveal hypoplasia (17/17). Misrouting was present in all nine tested patients. None of the patients had any signs of hypopigmentation of skin and hair. VA in albinism was better (median = 0.5 logMAR, IQR = 0.3-0.7, P 0.006) and the phenotypes were more variable: 14 of 132 without nystagmus, foveal hypoplasia grades 1 to 4, and misrouting absent in 16 of 74.CONCLUSIONS. Compared to albinism, the FHONDA syndrome appears to have a more narrow phenotypic spectrum, consisting of nonprogressive moderately to severely reduced VA, nystagmus, severe foveal hypoplasia, and misrouting. The co-occurrence of nystagmus, foveal hypoplasia, and misrouting in the absence of hypopigmentation implies that these abnormalities are not caused by lack of melanin, which has important implications for understanding the pathogenesis of these features. Show less
Purpose:The purpose of this study is to investigate the usefulness of neutral-density (ND) filters in cycloplegic-Plusoptix-photorefractor measurements.Methods:No-filter and ND-filter 0.04, 0.1 and... Show morePurpose:The purpose of this study is to investigate the usefulness of neutral-density (ND) filters in cycloplegic-Plusoptix-photorefractor measurements.Methods:No-filter and ND-filter 0.04, 0.1 and 0.2 cycloplegic-Plusoptix-photorefractor measurements were made in 42 hypermetropic eyes. Sphere, cylinder, spherical equivalent (SEQ), J0, and J45 values were compared.Results:Mean Plusoptix-photorefractor pupil sizes were 7.7 +/- 0.68 and 7.7 +/- 0.72 mm The no-filter failure rate was 16%, with 87% in pupils >7.8 mm. Mean no-filter sphere, cylinder, SEQ, J0 and J45 values were +0.34 +/- 0.35D, -0.29 +/- 0.22D, +0.20 +/- 0.36, -0.00 +/- 0.15, and +0.02 +/- 0.11, respectively. Only ND-filter-0.04 provided 5% more successful measurements and a clinically significant alteration in the percentage of values exceeding 0.5D for sphere and SEQ (-10% and -20%), but not for cylinder (+5%). Despite the increased accuracy, 21% of the spherical outcome exceeded 0.50D. Furthermore, the single-measure-intraclass-correlation-coefficient between no-filter and ND-filter-0.04 outcome was moderate (sphere 0.78 (0.62-0.87), cylinder 0.59 (0.35-0.75), SEQ 0.68 (0.48-0.82), J0 0.73 (0.54-0.84) and J45 0.57 (0.50-0.86)) and indicated significant individual variation. Bland-Altman-analyses indicated significant bias for sphere and SEQ; p=0.038 and p=0.030.Conclusion:ND-filter-0.04 resulted in a larger proportion of successful measurements and an increased accuracy. However, an unacceptable percentage of inaccuracy was still present compared to retinoscopy. There could be validity issues with the ND-filter 0.04 or the baseline no-filter readings at the start. We conclude that cycloplegic Plusoptix-photorefraction, even with the use of a 0.04 ND filter, is not a suitable method for exact objective refraction purposes in children. Show less
Purpose To compare the refractive outcome and residual accommodation with respect to various degrees of iris and skin pigmentation in hypermetropic children using 2 drops of cyclopentolate 1% (C +... Show morePurpose To compare the refractive outcome and residual accommodation with respect to various degrees of iris and skin pigmentation in hypermetropic children using 2 drops of cyclopentolate 1% (C + C) or 1 drop of cyclopentolate 1% and 1 drop of tropicamide 1% (C + T). Methods Two hundred fifty-one hypermetropic children were classified according to iris and skin pigmentation (light, medium, dark) and received randomized and double-blind C + C or C + T. Refractive error (spherical equivalent, SEQ) was determined using the Retinomax-K + 3. In 204 subjects, residual accommodation (RA) was determined using the PlusoptiX PowerRefractor. Results A linear mixed model with a light-irided and light skin-pigmented reference group receiving C + T (mean SEQ +3.10 +/- 1.87D) indicated significant less hypermetropia in subjects with a dark iris having a medium- and dark-pigmented skin in C + T, -1.02 +/- 0.29 (-1.59/-0.45) and -1.53 +/- 0.30 (-2.10/-0.95); and in subjects having a light-, medium- and dark-pigmented skin in C + C, -0.74 +/- 0.34 (-1.41/-0.06), -1.26 +/- 0.30 (-1.85/-0.66) and -1.84 +/- 0.30 (-2.42/-1.26). Similar findings were present for RA. Our model with a light-irided and light skin-pigmented reference group receiving C + T (mean RA +0.84 +/- 0.61D) indicated significantly higher RA in dark-irided subjects with medium- and dark-pigmented skin in C + T, +1.05 +/- 0.19 (+0.67/+1.43) and +1.35 +/- 0.20 (+0.9/+1.74), and in C + C, +1.13 +/- 0.21 (+0.71/+1.55) and +1.90 +/- 0.19 (+1.51/+2.28). Conclusions We found solid evidence that skin pigmentation rather than iris pigmentation is the decisive factor for effectiveness of cycloplegics. Awareness of the limitations of cycloplegic regimens in dark-irided/pigmented children is needed. Our study showed that cyclopentolate 1% combined with tropicamide 1% provides more accurate refractive outcomes both statistically and clinically integrating the factor skin pigmentation for dark-irided subjects. Show less
Introduction: Retinopathy of prematurity (ROP) remains an important cause for preventable blindness. Aside from gestational age (GA) and birth weight, risk factor assessment can be important for... Show moreIntroduction: Retinopathy of prematurity (ROP) remains an important cause for preventable blindness. Aside from gestational age (GA) and birth weight, risk factor assessment can be important for determination of infants at risk of (severe) ROP. Methods: Prospective, multivariable risk-analysis study (NEDROP-2) was conducted, including all infants born in 2017 in the Netherlands considered eligible for ROP screening by pediatricians. Ophthalmologists provided data of screened infants, which were combined with risk factors from the national perinatal database (Perined). Clinical data and potential risk factors were compared to the first national ROP inventory (NEDROP-1, 2009). During the second period, more strict risk factor-based screening inclusion criteria were applied. Results: Of 1,287 eligible infants, 933 (72.5%) were screened for ROP and matched with the Perined data. Any ROP was found in 264 infants (28.3% of screened population, 2009: 21.9%) and severe ROP (sROP) (stage >= 3) in 41 infants (4.4%, 2009: 2.1%). The risk for any ROP is decreased with a higher GA (odds ratio [OR] 0.59 and 95% confidence interval [CI] 0.54-0.66) and increased for small for GA (SGA) (1.73, 1.11-2.62), mechanical ventilation >7 days (2.13, 1.35-3.37) and postnatal corticosteroids (2.57, 1.44-4.66). For sROP, significant factors were GA (OR 0.37 and CI 0.27-0.50), SGA (OR 5.65 and CI 2.17-14.92), postnatal corticosteroids (OR 3.81 and CI 1.72-8.40), and perforated necrotizing enterocolitis (OR 7.55 and CI 2.29-24.48). Conclusion: In the Netherlands, sROP was diagnosed more frequently since 2009. No new risk factors for ROP were determined in the present study, apart from those already included in the current screening guideline. Show less
To describe the phenotype of Dutch patients with oculocutaneous albinism type 4 (OCA4), we collected data on pigmentation (skin, hair, and eyes), visual acuity (VA), nystagmus, foveal hypoplasia,... Show moreTo describe the phenotype of Dutch patients with oculocutaneous albinism type 4 (OCA4), we collected data on pigmentation (skin, hair, and eyes), visual acuity (VA), nystagmus, foveal hypoplasia, chiasmal misrouting, and molecular analyses of nine Dutch OCA4 patients from the Bartimeus Diagnostic Center for complex visual disorders. All patients had severely reduced pigmentation of skin, hair, and eyes with iris transillumination over 360 degrees. Three unrelated OCA4 patients had normal VA, no nystagmus, no foveal hypoplasia, and no misrouting of the visual pathways. Six patients had poor visual acuity (0.6 to 1.0 logMAR), nystagmus, severe foveal hypoplasia and misrouting. We found two novel variants in the SLC45A2 gene, c.310C>T; (p.Pro104Ser), and c.1368+3_1368+9del; (p.?). OCA4 patients of this Dutch cohort all had hypopigmentation of skin, hair, and iris translucency. However, patients were either severely affected with regard to visual acuity, foveal hypoplasia, and misrouting, or visually not affected at all. We describe for the first time OCA4 patients with an evident lack of pigmentation, but normal visual acuity, normal foveal development and absence of misrouting. This implies that absence of melanin does not invariably lead to foveal hypoplasia and abnormal routing of the visual pathways. Show less
Purpose Retinal oximetry measures oxygen saturation in retinal vessels. With the introduction of a mobile handheld prototype oximeter, this technique will become available for a broader patient... Show morePurpose Retinal oximetry measures oxygen saturation in retinal vessels. With the introduction of a mobile handheld prototype oximeter, this technique will become available for a broader patient population including bedridden patients and newborn babies. The objective is to determine the sensitivity of this handheld oximeter in room air and during isocapnic hyperoxia. A comparison is made between the handheld oximeter and the Oxymap T1.Methods Thirteen young healthy subjects with a mean age of 25 +/- 2 years were recruited at the Leiden University Medical Center. Retinal oximetry images were acquired during normoxia and during isocapnic hyperoxia for both the prototype oximeter and the OxymapT1. Isocapnic hyperoxia was induced with the dynamic end-tidal forcing technique. For both oximeters, the oxygen saturation and vessel width were measured with Oxymap Analyzer software. The hyperoxic state was verified with blood gas analysis.Results The mean oxygen saturation measured with the handheld oximeter in arterioles was 91.3% +/- 3.9% during normoxia and 94.6% +/- 3.9% during hyperoxia (p = 0.001). Oxygen saturation in venules was 56.3% +/- 9.8% during normoxia and 82.2 +/- 7.4% during hyperoxia (p < 0.001). For the Oxymap T1, the mean oxygen saturation for arterioles was 94.0% +/- 2.6% during normoxia and 95.4%+/- 3.2% during hyperoxia (p = 0.004). For the venules, the oxygen saturation was during normoxia 58.9%+/- 3.2% and 84.3 +/- 4.0% during hyperoxia (p 0.001).Conclusion The handheld retinal oximeter is sensitive to the changes in inhaled oxygen concentration. A small increase in oxygen saturation was measured in the arterioles and a larger increase in the venules. The handheld oximeter gives similar values as the 'gold standard' Oxymap T1 oximeter. Show less
Purpose To investigate the retinal structure and function in patients with CRB1-associated retinal dystrophies (RD) and to explore potential clinical endpoints.Methods In this prospective cross... Show morePurpose To investigate the retinal structure and function in patients with CRB1-associated retinal dystrophies (RD) and to explore potential clinical endpoints.Methods In this prospective cross-sectional study, 22 patients with genetically confirmed CRB1-RD (aged 6-74 years), and who had a decimal best-corrected visual acuity (BCVA) >= 0.05 at the last visit, were studied clinically with ETDRS BCVA, corneal topography, spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence, Goldmann visual field (VF), microperimetry, full-field electroretinography (ERG) and full-field stimulus testing (FST). Ten patients were from a genetic isolate (GI).Results Patients had retinitis pigmentosa (n = 19; GI and non-GI), cone-rod dystrophy (n = 2; GI) or macular dystrophy (n = 1; non-GI). Median age at first symptom onset was 3 years (range 0.8-49). Median decimal BCVA in the better and worse-seeing eye was 0.18 (range 0.05-0.83) and 0.08 (range light perception-0.72), respectively. Spectral-domain optical coherence tomography (SD-OCT) showed cystoid maculopathy in 8 subjects; inner retinal thickening (n = 20), a well-preserved (para)foveal outer retina (n = 7) or severe (para)foveal outer retinal atrophy (n = 14). All retinal layers were discernible in 13/21 patients (62%), with mild to moderate laminar disorganization in the others. Nanophthalmos was observed in 8 patients (36%). Full-field stimulus testing (FST) provided a subjective outcome measure for retinal sensitivity in eyes with (nearly) extinguished ERG amplitudes.Conclusions Despite the generally severe course of CRB1-RDs, symptom onset and central visual function are variable, even at advanced ages. Phenotypes may vary within the same family. Imaging and functional studies in a prospective longitudinal setting should clarify which endpoints may be most appropriate in a clinical trial. Show less
Nguyen, X.T.A.; Talib, M.; Cauwenbergh, C. van; Schooneveld, M.J. van; Fiocco, M.; Wijnholds, J.; ... ; Boon, C.J.F. 2021
Purpose: To investigate the natural history of RHO-associated retinitis pigmentosa (RP). Methods: A multicenter, medical chart review of 100 patients with autosomal dominant RHO-associated RP.... Show morePurpose: To investigate the natural history of RHO-associated retinitis pigmentosa (RP). Methods: A multicenter, medical chart review of 100 patients with autosomal dominant RHO-associated RP. Results: Based on visual fields, time-to-event analysis revealed median ages of 52 and 79 years to reach low vision (central visual field <20 degrees) and blindness (central visual field <10 degrees), respectively. For the best-corrected visual acuity (BCVA), the median age to reach mild impairment (20/67 <= BCVA < 20/40) was 72 years, whereas this could not be computed for lower acuities. Disease progression was significantly faster in patients with a generalized RP phenotype (n = 75; 75%) than that in patients with a sector RP phenotype (n = 25; 25%), in terms of decline rates of the BCVA (P < 0.001) and V4e retinal seeing areas (P < 0.005). The foveal thickness of the photoreceptor-retinal pigment epithelium (PR + RPE) complex correlated significantly with BCVA (Spearman's rho = 0.733; P < 0.001). Conclusion: Based on central visual fields, the optimal window of intervention for RHO-associated RP is before the 5th decade of life. Significant differences in disease progression are present between generalized and sector RP phenotypes. Our findings suggest that the PR + RPE complex is a potential surrogate endpoint for the BCVA in future studies. Show less
Purpose Compare patients treated for Retinopathy of Prematurity (ROP) in two consecutive periods. Methods Retrospective inventory of anonymized neonatal and ophthalmological data of all patients... Show morePurpose Compare patients treated for Retinopathy of Prematurity (ROP) in two consecutive periods. Methods Retrospective inventory of anonymized neonatal and ophthalmological data of all patients treated for ROP from 2010 to 2017 in the Netherlands, subdivided in period (P)1: 1-1-2010 to 31-3-2013 and P2: 1-4-2013 to 31-12-2016. Treatment characteristics, adherence to early treatment for ROP (ETROP) criteria, outcome of treatment and changes in neonatal parameters and policy of care were compared. Results Overall 196 infants were included, 57 infants (113 eyes) in P1 and 139 (275 eyes) in P2, indicating a 2.1-fold increase in ROP treatment. No differences were found in mean gestational age (GA) (25.9 +/- 1.7 versus 26.0 +/- 1.7 weeks, p = 0.711), mean birth weight (791 +/- 311 versus 764 +/- 204 grams, p = 0.967) and other neonatal risk factors for ROP. In P2, the number of premature infants born <25 weeks increased by factor 1.23 and higher oxygen saturation levels were aimed at in most centres. At treatment decision, 59.6% (P1) versus 83.5% (P2) (p = 0.263) infants were classified as Type 1 ROP (ETROP classification). Infants were treated with laser photocoagulation (98 versus 96%) and intravitreal bevacizumab (2 versus 4%). Retreatment was necessary in 10 versus 21 (p = 0.160). Retinal detachment developed in 6 versus 13 infants (p = 0.791) of which 2 versus 6 bilateral (p = 0.599). Conclusion In period 2, the number of infants treated according to the ETROP criteria (Type 1) increased, the number of ROP treatments, retinal detachments and retreatments doubled and the absolute number of retinal detachments increased. Neonatal data did not provide a decisive explanation, although changes in neonatal policy were reported. Show less
Purpose Photoscreening assesses risk factors for amblyopia, as an alternative to measurement of visual acuity (VA) to detect amblyopia, on the premise that its early correction could prevent... Show morePurpose Photoscreening assesses risk factors for amblyopia, as an alternative to measurement of visual acuity (VA) to detect amblyopia, on the premise that its early correction could prevent development of amblyopia. We studied implementations of Plusoptix photoscreening in existing population-based screening in Flanders and Iran. Methods In Flanders, VA is measured at age 3, 4 and 6, photoscreening was added to existing screening at age 1 and 2.5 years in 2013. In Iran, VA is measured at ages 3-6 years, photoscreening was added at ages 3-6 years between 2011 and 2016. Plusoptix use was analysed in the literature for detection of risk factors for amblyopia and amblyopia itself, for ages 0-3 and for 4-6. A questionnaire, containing seven domains: existing vision screening, addition of photoscreening, implementation in screening program, training, attendance, diagnosis and treatment, and costs was distributed. In Iran, screening procedures were observed on site. Results Implementation of Plusoptix photoscreening was mainly analysed from questionnaires and interviews, its effectiveness from literature data. In Flanders, of 56 759 children photoscreened at age one (81% of children born in 2013), 9.2% had been referred, 13% of these were treated, mostly with glasses, resulting in an increase of 4-year-old children wearing glasses from 4.7% to 6.4%. In Iran, 90% of children aged 3-6 years participated in vision screening in 2016, but only those who failed the vision test were subjected to photoscreening. Conclusions In Flanders, the use of Plusoptix photoscreening at ages 1 and 2.5 resulted in an increase of children wearing glasses, but it remains unknown how many cases of amblyopia have been prevented. Studies are needed to determine the relation between size and sort of refractive error and strabismus, and the increased chance to develop amblyopia. Show less
