Saskia M. Imhof

Age-related macular degeneration (AMD) shows substantial clinical heterogeneity that remains unexplained despite extensive genetic and clinical characterization. We evaluated whether proteomic stratification could provide insight beyond clinical phenotype and genetic risk. We performed 384-plex plasma proteomics in a cohort of 215 individuals, including patients with early and late neovascular AMD, other complement-associated retinal diseases, and age-matched controls. Proteome-based reclassification identified four disease-overarching clusters. Neovascular AMD cases were partitioned almost exclusively between two clusters (30/36). Early AMD cases were predominantly assigned to one of these clusters (10/18), whereas only two localized to the other (2/18). Both AMD-associated clusters shared elevated levels of a protein module enriched for lipoprotein-related functions compared to the other clusters. However, the cluster containing both early and neovascular AMD cases showed higher levels of additional protein modules enriched for complement pathways and cellular stress-response pathways compared with the other AMD-associated cluster. Importantly, this molecular divergence in neovascular AMD could not be explained by genetic predisposition (i.e., 52-variant AMD genetic risk score), signatures of biological ageing, nor by other clinical features. Together, these findings support two proteomic endotypes of neovascular AMD with distinct involvement of cellular stress pathways.

Purpose: To compare web-based, self-administered follow-up after cataract surgery to conventional face-to-face follow-up. Setting: Eye clinics in the Netherlands, Austria, and Germany. Design: Randomized controlled trial with an embedded method comparison study (ClinicalTrials.gov: NCT04809402). Methods: Routine patients with cataract were randomized into 2 groups: The telemonitoring group undertook web-based vision self-assessments and questionnaires from home, while the usual care group received conventional care. All participants had a 4- to 6-week postoperative clinic visit for safety and validation purposes. Outcomes included, the web test's accuracy for assessing postoperative visual acuity (VA) and refractive error, adverse event rates, and patient-reported outcome measurements (PROMs). Results: 94 participants (188 eyes) were enrolled. Web-based uncorrected distance VA testing demonstrated a negligible mean difference (−0.03 ± 0.14 logMAR) when compared with conventional Early Treatment Diabetic Retinopathy Study chart testing, with 95% limits of agreement ranging from −0.30 to 0.24 logMAR. The web-based refraction assessment overestimated the postoperative refractive error (mean difference in spherical equivalent 0.15 ± 0.67 diopters), resulting in a poorer corrected distance VA compared with subjective refraction (mean 0.1 vs −0.1 logMAR). Rates of adverse events and unscheduled consultations were minimal across both groups. Preoperative and postoperative PROM questionnaires had a 100% response rate. Visual functioning (Catquest-9SF and National Eye Institute Visual Function Questionnaire-25) improved postoperatively (mean improvement −0.80 and 16.70, respectively) and did not significantly differ between the 2 groups. Conclusions: The patients with cataract in this study effectively provided postoperative outcome data using a web interface. Both conventional and web-based follow-ups yielded similar PROMs and adverse event rates. Future developments should reduce the variability in the web-based VA test and yield representative refraction outcomes.

Background: The COVID-19 pandemic taught us how to rethink care delivery. It catalyzed creative solutions to amplify the potential of personnel and facilities. This paper presents and evaluates a promptly introduced triaging solution that evolved into a tool to tackle the ever-growing waiting lists at an academic ophthalmology department, the TeleTriageTeam (TTT). A team of undergraduate optometry students, tutor optometrists, and ophthalmologists collaborate to maintain continuity of eye care. In this ongoing project, we combine innovative interprofessional task allocation, teaching, and remote care delivery. Objective: In this paper, we described a novel approach, the TTT; reported its clinical effectiveness and impact on waiting lists; and discussed its transformation to a sustainable method for delivering remote eye care. Methods: Real-world clinical data of all patients assessed by the TTT between April 16, 2020, and December 31, 2021, are covered in this paper. Business data on waiting lists and patient portal access were collected from the capacity management team and IT department of our hospital. Interim analyses were performed at different time points during the project, and this study presents a synthesis of these analyses. Results: A total of 3658 cases were assessed by the TTT. For approximately half (1789/3658, 48.91%) of the assessed cases, an alternative to a conventional face-to-face consultation was found. The waiting lists that had built up during the first months of the pandemic diminished and have been stable since the end of 2020, even during periods of imposed lockdown restrictions and reduced capacity. Patient portal access decreased with age, and patients who were invited to perform a remote, web-based eye test at home were on average younger than patients who were not invited. Conclusions: Our promptly introduced approach to remotely review cases and prioritize urgency has been successful in maintaining continuity of care and education throughout the pandemic and has evolved into a telemedicine service that is of great interest for future purposes, especially in the routine follow-up of patients with chronic diseases. TTT appears to be a potentially preferred practice in other clinics and medical specialties. The paradox is that judicious clinical decision-making based on remotely collected data is possible, only if we as caregivers are willing to change our routines and cognitions regarding face-to-face care delivery.

BACKGROUND The COVID-19 pandemic taught us how to rethink care delivery. It catalyzed creative solutions to amplify the potential of personnel and facilities. This paper presents and evaluates a promptly introduced triaging solution that evolved into a tool to tackle the ever-growing waiting lists at an academic ophthalmology department, the TeleTriageTeam (TTT). A team of undergraduate optometry students, tutor optometrists, and ophthalmologists collaborate to maintain continuity of eye care. In this ongoing project, we combine innovative interprofessional task allocation, teaching, and remote care delivery. OBJECTIVE In this paper, we described a novel approach, the TTT; reported its clinical effectiveness and impact on waiting lists; and discussed its transformation to a sustainable method for delivering remote eye care. METHODS Real-world clinical data of all patients assessed by the TTT between April 16, 2020, and December 31, 2021, are covered in this paper. Business data on waiting lists and patient portal access were collected from the capacity management team and IT department of our hospital. Interim analyses were performed at different time points during the project, and this study presents a synthesis of these analyses. RESULTS A total of 3658 cases were assessed by the TTT. For approximately half (1789/3658, 48.91%) of the assessed cases, an alternative to a conventional face-to-face consultation was found. The waiting lists that had built up during the first months of the pandemic diminished and have been stable since the end of 2020, even during periods of imposed lockdown restrictions and reduced capacity. Patient portal access decreased with age, and patients who were invited to perform a remote, web-based eye test at home were on average younger than patients who were not invited. CONCLUSIONS Our promptly introduced approach to remotely review cases and prioritize urgency has been successful in maintaining continuity of care and education throughout the pandemic and has evolved into a telemedicine service that is of great interest for future purposes, especially in the routine follow-up of patients with chronic diseases. TTT appears to be a potentially preferred practice in other clinics and medical specialties. The paradox is that judicious clinical decision-making based on remotely collected data is possible, only if we as caregivers are willing to change our routines and cognitions regarding face-to-face care delivery.

Purpose: The aim of this study was to explore video-graded intraoperative risk factors for graft detachment (GD) and rebubbling in Descemet membrane endothelial keratoplasty surgery. Methods: A post hoc analysis of 65 eyes of 65 pseudophakic subjects with Fuchs endothelial dystrophy that underwent Descemet membrane endothelial keratoplasty surgery as part of the Advanced Visualization In Corneal Surgery Evaluation trial. All surgical recordings were assessed by 2 graders using a structured assessment form. A multinominal regression was performed to estimate the independent effect of video-graded intraoperative factors on the incidence of GD and rebubbling. Secondary outcomes are corrected distance visual acuity and endothelial cell density. Results: In total, 33 GDs were recorded, of which 17 required rebubbling. No significant predictors for GD or rebubbling were identified. However, the results revealed 2 clinically relevant patterns. An unfavorable graft configuration (ie, wrinkled, tight scroll, or taco-shaped) and a gas-bubble size smaller than the graft diameter were associated with an increased risk of GD [odds ratio (OR) 2.5 and OR 2.26, respectively] and rebubbling (OR 2.0 and OR 2.60, respectively). Inversely, a larger gas-bubble size was associated with a reduced risk of GD (OR 0.37) and rebubbling (OR 0.36). At 3 and 6 months postoperatively, corrected distance visual acuity was poorer in subjects requiring a rebubbling and endothelial cell density loss was higher in subjects with a partial GD. Conclusions: Our analysis revealed that the gas-bubble size and graft shape/geometry seem to be relevant clinical factors for GD and rebubbling, whereas descemetorhexis difficulty, degree of graft manipulation, graft overlap, and surgical iridectomy were not associated with an increased risk.

To this day, the most popular method of choice for testing visual field defects (VFDs) is subjective standard automated perimetry. However, a need has arisen for an objective, and less time-consuming method. Pupil perimetry (PP), which uses pupil responses to onsets of bright stimuli as indications of visual sensitivity, fulfills these requirements. It is currently unclear which PP method most accurately detects VFDs. Hence, the purpose of this study is to compare three PP methods for measuring pupil responsiveness. Unifocal (UPP), flicker (FPP), and multifocal PP (MPP) were compared by monocularly testing the inner 60 degrees of vision at 44 wedge-shaped locations. The visual field (VF) sensitivity of 18 healthy adult participants (mean age and SD 23.7 ± 3.0 years) was assessed, each under three different artificially simulated scotomas for approximately 4.5 minutes each (i.e. stimulus was not or only partially present) conditions: quadrantanopia, a 20-, and 10-degree diameter scotoma. Stimuli that were fully present on the screen evoked strongest, partially present stimuli evoked weaker, and absent stimuli evoked the weakest pupil responses in all methods. However, the pupil responses in FPP showed stronger discriminative power for present versus absent trials (median d-prime = 6.26 ± 2.49, area under the curve [AUC] = 1.0 ± 0) and MPP performed better for fully present versus partially present trials (median d-prime = 1.19 ± 0.62, AUC = 0.80 ± 0.11). We conducted the first in-depth comparison of three PP methods. Gaze-contingent FPP had best discriminative power for large (absolute) scotomas, whereas MPP performed slightly better with small (relative) scotomas.

The aim of this paper is to summarize all available evidence from systematic reviews, randomized controlled trials (RCTs) and comparative nonrandomized studies (NRS) on the association between nutrition and antioxidant, vitamin, and mineral supplements and the development or progression of age‐related macular degeneration (AMD). The Cochrane Database of Systematic Reviews, Cochrane register CENTRAL, MEDLINE and Embase were searched and studies published between January 2015 and May 2021 were included. The certainty of evidence was assessed according to the GRADE methodology. The main outcome measures were development of AMD, progression of AMD, and side effects. We included 7 systematic reviews, 7 RCTs, and 13 NRS. A high consumption of specific nutrients, i.e. β‐carotene, lutein and zeaxanthin, copper, folate, magnesium, vitamin A, niacin, vitamin B6, vitamin C, docosahexaenoic acid, and eicosapentaenoic acid, was associated with a lower risk of progression of early to late AMD (high certainty of evidence). Use of antioxidant supplements and adherence to a Mediterranean diet, characterized by a high consumption of vegetables, whole grains, and nuts and a low consumption of red meat, were associated with a decreased risk of progression of early to late AMD (moderate certainty of evidence). A high consumption of alcohol was associated with a higher risk of developing AMD (moderate certainty of evidence). Supplementary vitamin C, vitamin E, or β‐carotene were not associated with the development of AMD, and supplementary omega‐3 fatty acids were not associated with progression to late AMD (high certainty of evidence). Research in the last 35 years included in our overview supports that a high intake of specific nutrients, the use of antioxidant supplements and adherence to a Mediterranean diet decrease the risk of progression of early to late AMD.

Background: Children with a brain tumor are prone to develop visual impairment, which to date is often underestimated and unrecognized. Our aim was to assess the prevalence of ophthalmological evaluation and abnormal ophthalmological findings, and investigate whether demographic and tumor-related characteristics are associated with abnormal ophthalmological findings in children presenting with a primary brain tumor. Methods: Medical records of all 90 children diagnosed with a primary brain tumor between June 2018 and May 2019 and treated at the Princess Máxima Center for Pediatric Oncology, a tertiary referral center in the Netherlands, were retrospectively reviewed. Univariate regression analysis was used to investigate associations between demographic, tumor-related and clinical characteristics, and abnormal ophthalmological findings. Results: Sixty children (34 male [56.7%]; median [range] age, 9.3 [0–16.9] years) underwent ophthalmological evaluation within 6 weeks before or after diagnosis, 11 children (5 male [45.5%]; median [range] age, 5.7 [0.1–17.2] years) were seen more than 6 weeks before or after diagnosis, and 19 children (7 male [36.8%]; median [range] age, 7.2 [1.9–16.6] years) did not receive ophthalmological evaluation within at least 6 months from diagnosis. A total of 19 children (21.1%) presented with visual symptoms as first sign leading to the diagnosis of a brain tumor. Children who presented with visual symptoms (odds ratio [OR], 22.52; 95% confidence interval [CI], 4.90–103.60) and/or hydrocephalus (OR, 3.60; 95% CI, 1.38–9.36) at diagnosis were more often seen for ophthalmological evaluation. The most common abnormal ophthalmological findings were eye movement disorders (66.0%), papilledema (44.1%), and visual field defects (58.1%). Eye movement disorders occurred more frequently in patients with an infratentorial tumor (OR, 4.71; 95% CI, 1.03–21.65). The risk of papilledema was associated with older age (OR, 1.19; 95% CI, 1.05–1.34), hydrocephalus (OR, 9.63; 95% CI, 2.68–34.61), and infratentorial (OR, 9.11; 95% CI, 1.77–46.78) and supratentorial (OR, 13.13; 95% CI, 1.92–89.52) tumors. Conclusions: In this study, most children with a primary brain tumor underwent ophthalmological evaluation around diagnosis, 21% of the children were not evaluated. The high prevalence of abnormal ophthalmological findings stresses the importance of early standardized ophthalmological evaluation to detect visual impairment and provide timely treatment to potentially prevent permanent visual loss.

Waiting is commonplace in many areas of health care and has become a topical and politically important issue in the provision of healthcare services. Whilst managers and governments (the Treek agreement ('Treekoverleg') on benchmarking in the Dutch health services, 2000) search for solutions to this problem and have formulated norms for what they consider acceptable, there is little information concerning the clients' own opinions. An understanding of these could be an important consideration during policy-making and political discussions. In the ophthalmological clinic it has been established that the waiting lists for cataract surgery should not exceed 6 months because patients may experience negative outcomes if they have to wait longer than this. Solutions to the problems of long waiting can be found in the use of digital communication methods or integration of eye-care with other professionals such as general practitioners. In some cases, having to wait may actually have positive aspects.

Objective: To assess behavioural problems in retinoblastoma (RB) survivors.Methods: This population‐based cross‐sectional study included 148 RB survivors (8–35 years), registered in the Dutch national RB register. Survivors and parents were asked to fill in behavioural questionnaires. Prevalence rates were computed, based on both self‐reports and proxy reports. One‐sample T‐tests were applied to analyse differences compared with healthy reference samples. Multiple regression analyses were performed to identify predictors for behavioural problems within the RB sample.Results: Between‐group differences varied across informants and across age groups. Parents reported significantly elevated total problem behaviour in 30% of their offspring (aged 8–17 years); this against 9% in adolescents (12–17 years) and 12% in adults (18–35 years) based on self‐report. Parental reports showed significantly elevated rates of (1) internalising problems in boys and (2) somatic complaints in both girls and boys. Self‐reports indicate significantly lowered levels of (1) externalising problems in adolescent and adult women and (2) thought problems in female adolescents and in adult men. Especially survivors who suffered hereditary RB, who had undergone more intensive treatment, and who came from a single‐parent family were identified to be at most behavioural risk.Conclusion: Perception of severity and the nature of behavioural problems seem to differ between beholder, and to vary between age groups, if not between life stages. Health professionals should be aware that especially those who are confronted with hereditary RB and who subsequently undergo intensive treatment, and who grow up in broken families, run the risk of developing behavioural difficulties. Copyright © 2008 John Wiley & Sons, Ltd.