Retinal structure and visual pathway function at school age in children born extremely preterm: a population-based study.

BACKGROUND: Children born extremely preterm (gestational age < 28 weeks) show reduced visual function even without any cerebral or ophthalmological neonatal diagnosis. In this study, we aimed to assess the retinal structure with optical coherence tomography (OCT) and visual function with pattern-reversal visual evoked potentials (PR-VEPs) in a geographically defined population-based cohort of school-aged children born extremely preterm. Moreover, we aimed to explore the association between measures of retinal structure and visual pathway function in this cohort. METHODS: All children born extremely preterm from 2006-2011 (n = 65) in Central Norway were invited to participate. Thirty-six children (55%) with a median age of 13 years (range = 10-16) were examined with OCT, OCT-angiography (OCT-A), and PR-VEPs. The foveal avascular zone (FAZ) and circularity, central macular vascular density, and flow were measured on OCT-A images. Central retinal thickness, circumpapillary retinal nerve fibre layer (RNFL) and inner plexiform ganglion cell layer (IPGCL) thickness were measured on OCT images. The N70-P100 peak-to-peak amplitude and N70 and P100 latencies were assessed from PR-VEPs. RESULTS: Participants displayed abnormal retinal structure and P100 latencies (≥ 2 SD) compared to reference populations. Moreover, there was a negative correlation between P100 latency in large checks and RNFL (r = -.54, p = .003) and IPGCL (r = -.41, p = .003) thickness. The FAZ was smaller (p = .003), macular vascular density (p = .006) and flow were higher (p = .004), and RNFL (p = .006) and IPGCL (p = .014) were thinner in participants with ROP (n = 7). CONCLUSION: Children born extremely preterm without preterm brain injury sequelae have signs of persistent immaturity of retinal vasculature and neuroretinal layers. Thinner neuroretinal layers are associated with delayed P100 latency, prompting further exploration of the visual pathway development in preterms.

Visual function correlates with neurodevelopment in a population cohort of school-aged children born extremely preterm.

AIM: To investigate visual function and neurodevelopment in a geographically defined population cohort of school-aged children born extremely preterm. METHODS: All children born extremely preterm in Central Norway between 2006 and 2011 (n=65) were identified, and 36 (median age, min/max: 13, 10/16) were included. Best-corrected visual acuity (BCVA), contrast sensitivity (four spatial frequencies), parent-reported challenges and neuropsychological testing in learning, executive functions, motor skills, perception, reaction time, working and visual memory, processing speed, and pattern separation were measured. Brain MRI (3T) was acquired and read by a neuroradiologist. RESULTS: Median (min/max) BCVA letter score was 85 (35/91) in the better and 82 (13/89) in the worse eye. ROP participants (n=7) had lower contrast sensitivity in the two highest spatial frequencies (p = 0.024 and p = 0.004). Parent-reported challenges correlated negatively with BCVA (learning: p = 0.014; executive functions: p = 0.002; motor skills: p = 0.000; and perception: p = 0.001), while motor skills correlated negatively with one (p = 0.010) and perception with two (p = 0.003 and p = 0.009) of four spatial frequencies. Neuropsychological tests were reduced relative to norms. None had MRI-verified preterm brain injury. CONCLUSION: Visual function was subnormal and correlated with parent-reported challenges in a small cohort of extremely preterm school-aged children, indicating that visual function may be a marker of neurodevelopmental outcomes.

Cost consequences of task-shifting intravitreal injections from physicians to nurses in a tertiary hospital in Norway.

BACKGROUND: Anti-vascular endothelial growth factor is a medicine administered intravitreally by an injection to maintain visual acuity in patients with a variety of retinal diseases. The demand for this treatment has grown considerably in the westernized world the last two decades and will continue to increase due to an aging population. Because of the high volume, injections seize enormous resources and represent high costs for both hospitals and society. Task-shifting of injections from physicians to nurses may be a means to reduce such costs, however the magnitude of possible savings has been poorly investigated. To this end we investigated changes in the hospital costs per injection, six-year cost projections of physician- versus nurse-administered injections for a Norwegian tertiary hospital and we compared the societal costs per patient per year. METHODS: Patients (n = 318) were randomized to either physician- or nurse administered injections, and data were prospectively collected. Hospital costs per injection were calculated as the sum of training costs, personnel time and running expenses. The number of injections for the years 2014 - 21 from a Norwegian tertiary hospital was combined with age group specific injection prevalence and population projections to calculate cost projections for 2022 - 27. Societal costs per patient were calculated as the sum of hospital costs, transport costs for patients, caregivers' use of time, costs of ophthalmology consultations and community-based homecare. RESULTS: The hospital costs per injection were 5.5 € higher for physicians compared to nurses (281.6 € versus 276.1 €). Cost projections estimated an annual hospital saving of task-shifting of 48 921 € for 2022 - 27. Societal costs per patient did not differ significantly between the two groups (mean 4988 € vs 5418 €, p = 0.398). CONCLUSION: Task-shifting of injections from physicians to nurses can reduce hospital costs and increase the flexibility of physician resources. The annual savings are modest, but increased demand for injections might increase future cost savings. To achieve future savings for society, organizing ophthalmology consultations and injections on the same day to reduce the number of visits might be a solution. TRIAL REGISTRATION: ClinicalTrials.gov NCT02359149 (09/02/2015).

Visuopathy of prematurity: is retinopathy just the tip of the iceberg?

Research on retinopathy of prematurity (ROP) focuses mainly on the abnormal vascularization patterns that are directly visible for ophthalmologists. However, recent findings indicate that children born prematurely also exhibit changes in the retinal cellular architecture and along the dorsal visual stream, such as structural changes between and within cortical areas. Moreover, perinatal sustained systemic inflammation (SSI) is associated with an increased risk for ROP and the visual deficits that follow. In this paper, we propose that ROP might just be the tip of an iceberg we call visuopathy of prematurity (VOP). The VOP paradigm comprises abnormal vascularization of the retina, alterations in retinal cellular architecture, choroidal degeneration, and abnormalities in the visual pathway, including cortical areas. Furthermore, VOP itself might influence the developmental trajectories of cerebral structures and functions deemed responsible for visual processing, thereby explaining visual deficits among children born preterm.

STRUCTURAL PATHOLOGY AFTER RETINAL DETACHMENT: Multicolor Confocal Scanning Laser Ophthalmoscopy Versus Color Fundus Photography.

PURPOSE: To compare pathology detection using multicolor confocal scanning laser ophthalmoscopy with color fundus photography following macula-off rhegmatogenous retinal detachment. METHODS: Postsurgery multicolor confocal scanning laser ophthalmoscopy and color fundus photography images from 30 rhegmatogenous retinal detachment patients were examined by 10 masked graders. Imaging was performed with the Heidelberg Spectralis HRA and the digital retinal camera Basler acA2500-14gc GigE. Swept-source optical coherence tomography was used as verification modality. Detection rates of ellipsoid zone disruption, foveal ellipsoid zone rosette, outer retinal folds, intraretinal cysts, subretinal fluid layer, subretinal fluid blebs, retinal striae, and retinal detachment line were compared. Intermodality and intergrader agreement were estimated. RESULTS: Overall pathology detection was significantly higher for multicolor confocal scanning laser ophthalmoscopy multicolor confocal scanning laser ophthalmoscopy (adjusted odds ratio = 7.39; 95% confidence interval, 1.64-33.30; P = 0.009). The intermodality and intergrader agreement on overall pathology detection were moderate. The intermodality agreement was 0.49 (95% confidence interval, 0.48-0.51; P < 0.0001) (Gwet's AC1). Intergrader agreement was 0.53 (95% confidence interval, 0.52-0.54; P < 0.0001) for multicolor confocal scanning laser ophthalmoscopy and 0.58 (95% confidence interval, 0.57-0.59; P < 0.0001) (Fleiss kappa) for color fundus photography. CONCLUSION: Multicolor confocal scanning laser ophthalmoscopy imaging is superior to color fundus photography in detecting and delineating structural retinal abnormalities following rhegmatogenous retinal detachment and can be a helpful tool in the visualization of retinal remodeling processes in patients recovering from rhegmatogenous retinal detachment surgery.

Task shifting of intravitreal injections from physicians to nurses: a qualitative study.

BACKGROUND: Intravitreal injections of anti-vascular endothelial growth factor are high-volume procedures and represent a considerable workload on ophthalmology departments. Several departments have tried to meet this increase by shifting the task to nurses. To maintain high-quality patient care, we developed a training program for nurses that certifies them to administer injections. This qualitative study aimed to evaluate whether the nurses were confident and in control after participating in the training program and whether they were satisfied with the training and the new task. METHODS: Between 2014 and 2018, 12 registered nurses were trained in a tertiary hospital in central Norway. All the nurses were interviewed, either individually (n = 7) or in a group (n = 5). We analysed the interviews using Graneheim and Lundman's qualitative content analysis. RESULTS: Eight subthemes were clustered within four main themes: 1) procedure and challenges, 2) motivation, 3) cooperation and confidence, and 4) evaluation. The nurses felt confident and in control when administering injections but experienced moments of insecurity. The new task gave the nurses a sense of achievement, and they highlighted improvement of patients' lives as positive. A greater level of responsibility gave the nurses pride in their profession. They had suggestions that could improve training efficiency but were overall satisfied with the training program. CONCLUSIONS: Our study showed that the nurses were satisfied with the training and that learning a new task led to higher self-esteem and increased respect from patients and colleagues. Suggestions to improve the training were identified; these should be considered before implementation by other departments.

Skin-to-skin contact during eye examination did not reduce pain compared to standard care with parental support in preterm infants.

AIM: We compared the pain relieving effect of skin-to-skin contact versus standard care in the incubator during screening for retinopathy of prematurity. METHODS: This randomised crossover study included 35 preterm infants of less than 32 weeks of gestational age admitted to St Olavs University Hospital, Trondheim, Norway, between January 2014 and June 2016. Randomisation was for skin-to-skin with one of the parents or standard care with supportive positioning by parents for the first of two consecutive eye examinations. The pain score was measured twice using the Premature Infant Pain Profile (PIPP) during and after the eye examination. The infants' movement activity was video recorded after the examination. RESULTS: There was no difference in mean pain scores with skin-to-skin contact versus standard care during (10.2 vs. 10.3, p = 0.91) or after (7.0 vs. 6.8, p = 0.76) the procedure. Independent of the randomisation group, PIPP scores were lower than previous comparable studies have found. Bouts of movement activity were also the same whether the examination was conducted in skin-to-skin position or in the incubator (p = 0.91). CONCLUSION: Skin-to-skin contact during the eye examination did not provide additional pain relief compared to standard care where the parents were already a part of the multidimensional approach.

Retinopathy of prematurity: inflammation, choroidal degeneration, and novel promising therapeutic strategies.

Retinopathy of prematurity (ROP) is an important cause of childhood blindness globally, and the incidence is rising. The disease is characterized by initial arrested retinal vascularization followed by neovascularization and ensuing retinal detachment causing permanent visual loss. Although neovascularization can be effectively treated via retinal laser ablation, it is unknown which children are at risk of entering this vision-threatening phase of the disease. Laser ablation may itself induce visual field deficits, and there is therefore a need to identify targets for novel and less destructive treatments of ROP. Inflammation is considered a key contributor to the pathogenesis of ROP. A large proportion of preterm infants with ROP will have residual visual loss linked to loss of photoreceptor (PR) and the integrity of the retinal pigment epithelium (RPE) in the macular region. Recent studies using animal models of ROP suggest that choroidal degeneration may be associated with a loss of integrity of the outer retina, a phenomenon so far largely undescribed in ROP pathogenesis. In this review, we highlight inflammatory and neuron-derived factors related to ROP progression, as well, potential targets for new treatment strategies. We also introduce choroidal degeneration as a significant cause of residual visual loss following ROP. We propose that ROP should no longer be considered an inner retinal vasculopathy only, but also a disease of choroidal degeneration affecting both retinal pigment epithelium and photoreceptor integrity.

Postnatal systemic inflammation and neuro-ophthalmologic dysfunctions in extremely low gestational age children.

AIM: Compared to infants born at term, children born very preterm are at increased risk of visual dysfunctions and neonatal systemic inflammation. Here, we explore whether these two propensities are related. METHODS: As part of the ELGAN study, the concentrations of 16 mediators of inflammation were measured in blood obtained on postnatal days 1, 7, 14, 21 and 28 from 1062 children born before the 28th week of gestation. Presence of visual field deficit, strabismus and/or impaired visual fixation was recorded at age two. The concentrations of each protein were divided into quartiles within gestational week categories. We calculated odds ratios with 99% confidence intervals for having each disorder comparing children with concentration in the top quartile of each protein to children whose concentration was in the lower quartiles on the corresponding day. Analyses were adjusted for gestational age and birth weight Z-score. RESULTS: Only one of 80 assessments (16 proteins on five different days) was significant for visual field deficit, and one for impaired fixation. No association was found between strabismus and any inflammatory mediator. CONCLUSION: None of the three neuro-ophthalmologic dysfunctions assessed at two years appears to be associated with systemic inflammation measured the first four postnatal weeks.

Nurse-administered intravitreal injections of anti-VEGF: study protocol for noninferiority randomized controlled trial of safety, cost and patient satisfaction.

BACKGROUND: Intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) now improve or stabilize visual acuity in a number of previously untreatable eye diseases, of which the main are age-related macular degeneration, retinal vein occlusion and diabetic macular edema. Most patients require multiple injections over lengthy periods of time and the prevalence of treatable conditions is increasing. Anti-VEGF IVI normally administered by physicians, therefore represent a considerable workload on ophthalmologic clinics and will continue to do so in the near future. Nurse-administered IVI may relieve this workload, but the safety, cost and patient satisfaction of such an extended role for nurses in ophthalmologic clinics has not earlier been investigated. To investigate these outcomes following independent anti-VEGF IVI by trained nurses, a noninferiority randomized controlled trial is being conducted. METHODS/DESIGN: Patients eligible for anti-VEGF treatment, minimum 304, are recruited and randomized to IVI administration by either trained nurses or physicians. The primary outcome is safety, measured by difference in mean change in visual acuity between the two groups during an observation period of 12 months. Secondary outcomes are incidence of ocular adverse events, cost per patient and patient satisfaction. DISCUSSION: This study protocol describes the design of the first randomized controlled trial of nurse-administered IVI of anti-VEGF. The study is designed to examine safety, cost and patient satisfaction during 12 months follow-up. TRIAL REGISTRATION: ClinicalTrials.gov NCT02359149 . Registered February 4, 2015.

Foveal thickness and its association with visual acuity in adults born preterm with very low birth weight: A two-country birth cohort study.

PURPOSE: To explore foveal and parafoveal thickness in adults born preterm with very low birth weight (VLBW) and its association with best-corrected visual acuity (BCVA) and gestational age (GA) compared to adults born at term. METHODS: In a joint study of the Helsinki Study of Very Low Birth Weight Adults (Finland) and the NTNU Low Birth Weight Life study (Norway), 106 VLBW and 143 term-born controls were examined with spectral-domain optical coherence tomography and BCVA at age 31-43 years. Thickness of retinal layers was segmented in the foveal and parafoveal areas of the macula. RESULTS: The total retinal thickness in the foveal area was thicker in VLBW adults compared with controls; mean (SD): 292.5 µm (28.2) and 272.4 µm (20.2); p < 0.001, and thinner in the parafoveal areas of the macula. These findings could be explained by a thicker inner retinal layer in the foveal area found in VLBW adults compared with controls (mean difference 20.4 µm; CI: 15.0 to 25.9), where a thicker fovea was associated with lower GA, but not BCVA. CONCLUSION: Adults born preterm with VLBW had a thicker retina in the foveal area than controls and this was associated with GA, but not with BCVA. These changes seem to be related to a thicker inner retinal layer in VLBW adults. The findings imply that signs of macular underdevelopment are still present in adulthood, but not necessarily related to reduced visual function.

Visual function in adults born preterm with very low birth weight-A two-country birth cohort study.

PURPOSE: The purpose of the study was to investigate visual function and vision-related general health in adults that were born preterm with very low birth weight (VLBW: birth weight < 1500 g) in their 30s-40s. METHODS: We recruited 137 adults born preterm with VLBW and 158 term-born controls aged 31-43 years from two birth cohorts: the Helsinki Study of Very Low Birth Weight Adults (Finland) and the NTNU Low Birth Weight in a Lifetime Perspective study (Norway). We used neonatal data and measured refraction, best-corrected visual acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, contrast sensitivity, visual fields, intraocular pressure (IOP), self-reported vision-targeted health status with the National Eye Institute Visual Function Questionnaire-25. RESULTS: VLBW adults had a lower BCVA ETDRS score than controls: mean (SD) better eye 86.7 (13.4) versus 90.2 (4.4), p = 0.02; mean (SD) worse eye 82.3 (14.9) versus 87.6 (4.6), p = 0.003. VLBW adults also had lower contrast sensitivity thresholds in several spatial frequencies and scored lower than controls in eight out of the 12 subscales of self-reported vision-targeted health status. Refraction, visual fields and IOP were similar between groups. Two VLBW participants were blind. None had been treated for retinopathy of prematurity. CONCLUSION: We suggest that lower visual function and vision-related health represent life-long consequences of prematurity and VLBW in the studied 31- to 43-year-old cohort. The underlying mechanisms remain to be determined.

Visual outcomes and their association with grey and white matter microstructure in adults born preterm with very low birth weight.

Individuals born with very low birth weight (VLBW; < 1500 g) have a higher risk of reduced visual function and brain alterations. In a longitudinal cohort study, we assessed differences in visual outcomes and diffusion metrics from diffusion tensor imaging (DTI) at 3 tesla in the visual white matter pathway and primary visual cortex at age 26 in VLBW adults versus controls and explored whether DTI metrics at 26 years was associated with visual outcomes at 32 years. Thirty-three VLBW adults and 50 term-born controls was included in the study. Visual outcomes included best corrected visual acuity, contrast sensitivity, P100 latency, and retinal nerve fibre layer thickness. Mean diffusivity, axial diffusivity, radial diffusivity, and fractional anisotropy was extracted from seven regions of interest in the visual pathway: splenium, genu, and body of corpus callosum, optic radiations, lateral geniculate nucleus, inferior-fronto occipital fasciculus, and primary visual cortex. On average the VLBW group had lower contrast sensitivity, a thicker retinal nerve fibre layer and higher axial diffusivity and radial diffusivity in genu of corpus callosum and higher radial diffusivity in optic radiations than the control group. Higher fractional anisotropy in corpus callosum areas were associated with better visual function in the VLBW group but not the control group.

Patient satisfaction following a switch from treat-and-extend to observe-and-plan regimen in age-related macular degeneration.

OBJECTIVE: Standard treatment of neovascular age-related macular degeneration (nAMD) is intravitreal injections (IVI) of antivascular endothelial growth factor (anti-VEGF) according to treat-and-extend (TnE). Observe-and-plan (OnP), a new regimen based on each individual's relapse interval lead to fewer clinical visits and has so far shown to be safe in treatment-naïve patients. In this study, we explore patient satisfaction and safety in nAMD when switching from TnE to OnP. METHODS AND ANALYSIS: 38 participants treated acording to TnE for ≥12 months were included and switched from TnE to OnP with their last stable interval. Main outcome was patient satisfaction (Leeds Satisfaction Questionnaire). Secondary outcomes were best-corrected visual acuity (BCVA), central retinal thickness (CRT) before and 12 months after switch and number of monitoring visits and injections of anti-VEGF 12 months prior to and following switch. RESULTS: Mean patient satisfaction was higher (3.7±0.5 SD) at 12 months after switch from TnE to OnP than before (3.6±0.5 SD, p=0.009, response rate 76%). BCVA and CRT were unchanged. Number of monitoring visits and injections were lower in the 12 months following than prior to switch (p<0.001). CONCLUSION: A switch from TnE to OnP in a non-treatment-naïve population resulted in higher patient satisfaction, while maintaining stable BCVA. This indicates that OnP may be applicable in the large group of nAMD patients that have received IVI for several years. OnP may alleviate the treatment burden on both individual and society of frequent clinical visits while increasing patient satisfaction.

Air versus Sulfur Hexafluoride Gas Tamponade for Small and Medium-Sized Macular Holes: A Randomized Noninferiority Trial.

PURPOSE: To investigate whether air tamponade is noninferior to sulfur hexafluoride (SF6) gas tamponade for small (≤ 250 µm) and medium-sized (> 250 µm and ≤ 400 µm) macular holes (MHs). DESIGN: Multicenter, randomized controlled, noninferiority trial. PARTICIPANTS: Patients aged ≥ 18 years undergoing surgery for primary MHs of ≤ 400 µm in diameter. METHODS: The patients in both groups underwent conventional pars plana vitrectomy with peeling of the internal limiting membrane. At the end of the surgery, the patients were randomized to receive either air or SF6 gas tamponades, stratified by MH size. Postoperatively, the patients followed a nonsupine positioning regimen for 3 days. MAIN OUTCOME MEASURES: The primary end point was the MH closure rate after a single surgery, confirmed by OCT after 2 to 8 weeks. The noninferiority margin was set at a 10-percentage-point difference in the closure rate. RESULTS: In total, 150 patients were included (75 in each group). In the intention-to-treat (ITT) analysis, 65 of 75 patients in the air group achieved primary closure. All 75 MHs in the SF6 group closed after a single surgery. Six patients were excluded from the per-protocol (PP) analysis. In the PP analysis, 63 of 70 patients in the air group and all 74 patients in the SF6 group achieved MH closure after a single surgery, resulting in closure rates of 90% (95% confidence interval [CI], 79.9%-95.5%) and 100% (95% CI, 93.9%-100%), respectively. For the difference in closure rates, the lower bound of a 2-sided 95% CI exceeded the noninferiority margin of 10% in both ITT and PP analyses. In the subgroups of small MHs, all 20 patients in the air group and all 28 patients in the SF6 group achieved primary closure. CONCLUSIONS: This prospective randomized controlled trial proved that air tamponade is inferior to SF6 tamponade for MHs of ≤ 400 µm in diameter.

A Systematic Switch From Originator Infliximab to Biosimilar Infliximab in Patients With Non-Infectious Uveitis.

PURPOSE: To investigate the efficacy of biosimilar infliximab compared to that of the originator infliximab for the treatment of chronic non-infectious uveitis. DESIGN: Before-and-after study. METHODS: All patients in the Central Norway Health Region between 2007 and 2018 were included. They were switched from originator to biosimilar infliximab therapy from 2014 to 2017. The primary outcome was quiescence of uveitis before and after the switch. All patients were seen every 1-3 months. Visits were binned into 3-month long periods for each patient takingboth medications. Poisson regression analysis was used to estimate the incidence rate ratio (IRR) of quiescence between the 2 treatments. RESULTS: Twenty-nine patients were treated with infliximab. Twenty-three of those patients were switched from originator to biosimilar infliximab. The majority were white (87%), female (92%), and had chronic anterior uveitis (65%). For patients taking the originator and biosimilar drugs, the median treatment duration was38 months (range: 8-131 months) and 15 months (range: 5-55 months), respectively. Concomitant immunosuppressive medications and topical and oral steroids were used similarly during treatment with both originator and biosimilar infliximab. The IRR for quiescence was 0.91 (95% confidence intervals [CI]: 0.7-1.1; P = 0.38), which indicated no statistically significant differences in achieving quiescence after the switch. Also, there were no differences in the incidence rate of flare events with the switch (IRR: 1.04; 95% CI: 0.36-2.98; P = 0.95). IRR adjusted for intraocular surgery was 0.90 (95% CI: 0.7-1.1; P = 0.37). CONCLUSIONS: No evidence of differences in effectiveness were found in comparing biosimilar to originator infliximab in patients with chronic non-infectious uveitis.

Stable incidence but regional differences in retinopathy of prematurity in Norway from 2009 to 2017.

PURPOSE: To explore the changes over time and regional differences in the incidence of retinopathy of prematurity (ROP) in a national cohort of infants born <28 weeks' gestational age (GA). METHODS: A population-based study of infants with GA <28 weeks in Norway from 2009 to 2017. Prospectively collected data on clinical variables and outcomes were obtained from the Norwegian Neonatal Network. RESULTS: Of 1499 live-born infants transferred to a neonatal intensive care unit, 1156 were discharged alive. Four-hundred and fifty-eight infants (39.6%) had ROP, 152 (13.1%) had severe ROP, and 110 (9.5%) were treated for ROP. Eleven hundred infants (95.2%) had complete data sets. In a model comprising region of primary care, GA [odds ratios (OR): 0.65; 95% CI: 0.55-0.77], growth velocity (OR: 1.10; 95% CI: 1.00-2.00), medically treated patent ductus arteriosus (OR: 1.80; 95% CI: 1.19-2.72), weeks of supplemental oxygen (OR: 1.07; 95% CI: 1.03 to 1.11) and region of primary care (OR: 4.95; 95% CI: 3.05-8.04 for the pair of regions with the highest estimated OR) were significantly associated with severe ROP. Additionally, institutional differences for severe ROP were found, with ORs from 0.41 (95% CI: 0.05-3.23) to 5.36 (95% CI: 3.05-9.43) using the largest institution as reference. Incidences were stable over time after adjusting for GA. A larger proportion was treated with anti-vascular endothelial growth factor after 2011. CONCLUSIONS: The incidence of severe ROP was stable between 2009 and 2017 in Norway. Regional and institutional differences need to be explored in future studies.

Clinical features and molecular genetics of patients with ABCA4-retinal dystrophies.

PURPOSE: Pathogenic variations in the ABCA4 gene are a leading cause of vision loss in patients with inherited retinal diseases. ABCA4-retinal dystrophies are clinically heterogeneous, presenting with mild to severe degeneration of the retina. The purpose of this study was to clinically and genetically characterize patients with ABCA4-retinal dystrophies in Norway and describe phenotype-genotype associations. METHODS: ABCA4 variants were detected in 111 patients with inherited retinal disease undergoing diagnostic genetic testing over a period of 12 years. In patients where only a single ABCA4 variant was found, whole-gene ABCA4 sequencing was performed and intronic variants were investigated by mRNA analyses in fibroblasts. Medical journals were used to obtain a clinical description and ultrawidefield autofluorescence images were used to analyse retinal degeneration patterns. RESULTS: The genetic diagnostic yield was 89%. The intronic splice variant c.5461-10T>C was the most prevalent disease-causing variant (27%). Whole-gene ABCA4 sequencing detected two novel intronic variants (c.6729+81G>T and c.6817-679C>A) that we showed affected mRNA splicing. Peripheral retinal degeneration was identified in 33% of patients and was associated with genotypes that included severe loss of function variants. By contrast, peripheral degeneration was not found in patients with a disease duration over 20 years and genotypes including p.(Asn1868lle), c.4253+43G>A or p.(Gly1961Glu) in trans with a loss of function variant. CONCLUSION: This study demonstrates the clinical and genetic heterogeneity of ABCA4-retinal dystrophies in Norway. Further, the study presents novel variants and increases our knowledge on phenotype-genotype associations and the presence of peripheral retinal degeneration in ABCA4-retinal dystrophy patients.

Drusenoid pigment epithelial detachment volume is associated with a decrease in best-corrected visual acuity and central retinal thickness: the Norwegian Pigment Epithelial Detachment Study (NORPED) report no. 1.

PURPOSE: To investigate the association of drusenoid pigment epithelial detachment (DPED) volume and change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) during the growth phase of large DPEDs. METHODS: Patients from an ongoing prospective observational study, the Norwegian Pigment Epithelial Detachment Study (NORPED), with 1 year of follow-up and DPEDs ≥1000 µm in diameter, examined with the Heidelberg Spectralis HRA-OCT were included. Patients with DPEDs in the regression phase were excluded. Multicolour, near-infrared reflectance, optical coherence tomography (OCT) and OCT angiography images were obtained every 6 months. Fluorescein angiography and indocyanine green angiography were performed at baseline and yearly to exclude choroidal neovascularization (CNV). RESULTS: Forty-four patients and 66 eyes were included. In the statistical model for BCVA, every 1.0 mm3 increase in DPED volume led to a decrease in BCVA of 4.0 ETDRS letters (95% CI, -7.0 to -1.0, p = 0.008). A decrease in BCVA was significantly associated with older patient age, the presence of acquired vitelliform lesions and subfoveal location of the DPEDs. In the model for CRT, every 1.0 mm3 increase in DPED volume led to a decrease in CRT of 26.7 µm (95% CI, -44.4 to -9.0, p = 0.003). Two eyes had progression of geographic atrophy and none developed CNV. CONCLUSION: The increasing volume of DPEDs during the growth phase is associated with a decrease in BCVA and CRT. The subfoveal location of DPEDs and the presence of acquired vitelliform lesions appear to be associated with a further reduction in BCVA.