Injection burden and treatment intervals of aflibercept in observe-and-plan regimen for neovascular age-related macular degeneration.

PURPOSE: The Observe-and-Plan (O&P) regimen allows for individualised treatment. In this study, we evaluated injection burden and intervals using aflibercept in an O&P regimen for eyes with neovascular age-related macular degeneration (AMD). METHODS: This was a retrospective registry-based study of treatment-naïve eyes with neovascular AMD. Treatment data were compiled for 3 years after commencement of intravitreal aflibercept therapy. We evaluated clinical consequences at the first follow-up after loading dose, the proportion of patients who obtained and kept dry macula after loading dose, number of injections and intervals between injections. RESULTS: Data were obtained for 1103 eyes. After loading dose, 0.4% were lost to follow-up, 7.5% discontinued, 50.9% booked for further injections and 41.3% booked for monthly observations. After loading dose, the macula remained dry in 49.2% at 3 months, 34.0% at 6 months, 23.7% at 12 months and 15.2% at 24 months. For the entire population, median cumulative total number of injections was 7, 12 and 15, after 1, 2 and 3 years, respectively. After the 3rd year, the proportion of eyes in the short 4-6 weeks treatment interval was 51.1%, 8 weeks interval was kept in 14.4% and the extended treatment intervals of 10 and 12 weeks was possible in 34.4%. CONCLUSION: After loading dose, one in two eyes required further injections. A large proportion required therapy with shorter intervals than the label-recommended 8 weeks. The large majority of those who obtained a dry macula after loading dose turned exudative again, mostly within the first 3 months.

Blindness is decreasing among children born preterm during the last four decades in Denmark.

PURPOSE: Children born preterm are believed to be at increased risk of visual impairment (VI). The increased survival rate of extremely preterm children may have changed the spectrum of diseases occurring postnatally. The aim of this study was to analyse the prevalence and causes of VI in an ex-preterm Danish population during the last 4 decades. METHODS: The study was based on the National Register of Blind and Visually Impaired Children (NRVIC). Ex-preterms born at gestational age (GA) <32 weeks and enrolled in NRVIC at any time between 1988 and 2020 were included. The main cause of VI, the severity of VI and systemic comorbidities were analysed for temporal changes. RESULTS: A total of 335 patients were included. The prevalence of VI decreased from 26/1000 preterm children in the 1980s to 15/1000 in 2000s. Blindness due to preterm birth is almost eliminated affecting 1/1000 today. Sequelae to retinopathy of prematurity (ROP) was the most common cause of VI (51% of cases) in the 1980s but decreased to 34% in 2010s, whereas non-ocular causes of VI increased from 1% to 36%, respectively. More than half of the children (64%) had combined comorbidities and 36% had isolated VI. CONCLUSION: The improved monitoring in neonatal intensive care units and management of ROP has reduced the prevalence of severe VI due to ROP and almost eliminated blindness over the last decades in Denmark. However, preterm children are still at risk of non-ocular causes of VI and comorbidities following the premature delivery.

Prognostic modelling of number of patients with retinal vein occlusion in anti-VEGF therapy.

PURPOSE: The purpose of the study was to evaluate temporal changes in age- and sex-stratified incidence rates of retinal vein occlusion (RVO) commenced in anti-vascular endothelial growth factor (anti-VEGF) treatment, proportion of patients remaining in active anti-VEGF therapy over time, and to develop a forecasting model for future number of patients with RVO in active anti-VEGF therapy. METHODS: This was a registry-based study of patients with RVO in the Capital Region of Denmark from commenced in anti-VEGF therapy from 1 January 2007 to 30 June 2022. Census data were extracted from Statistics Denmark for incidence rate analyses and forecasting data of future demographics. RESULTS: A total of 2641 patients with RVO were commenced in anti-VEGF therapy, of which 2192 were later discontinued. Number of patients rose dramatically during the first years of introduction of anti-VEGF therapy, after which growth was slower and followed the demographic changes. Trend analyses revealed that the COVID-19 epidemics impacted with fewer referrals and more aggressive discontinuation practices. Annual incidence of RVO in 2012-2021 was 13.1 per 100 000 (95% CI: 12.6-13.6 per 100 000). Proportion of patients with RVO remaining in active anti-VEGF treatment was 55.0%, 40.1%, 30.8% and 12.1% after Years 1, 2, 3 and 8, respectively. According to our forecast, number of patients with RVO in active anti-VEGF therapy will grow slowly but continually at least until year 2035. CONCLUSION: Our study reports incidence rates and provides prognostic modelling of number of patients with RVO in anti-VEGF therapy.

Finding Ophthalmic Risk and Evaluating the Value of Eye exams and their predictive Reliability (FOREVER)-A cohort study in a Danish high street optician setting: Design and methodology.

PURPOSE: The purpose of the study was to describe the rationale and design of Project FOREVER (Finding Ophthalmic Risk and Evaluating the Value of Eye exams and their predictive Reliability). DESIGN: Project FOREVER will build a comprehensive database of clinical eye and vision data collected from ~280 000 adults at 100 optician stores across Denmark. The FOREVER database (FOREVERdb) includes detailed data from refraction, visual acuity, intraocular pressure, corneal thickness, visual field assessments and retinal fundus images. Linkage to the comprehensive Danish national registries with, that is diagnostic and prescribing data permits investigation of rare associations and risk factors. 30 000 individuals over 50 also provide a saliva sample for later genetic studies and blood pressure measurements. Of these 30 000, 10 000 will also get optical coherence tomography (OCT) nerve and retinal scans. This subpopulation data is reviewed by ophthalmologists for disease detection. All participants will be asked to complete a questionnaire assessing lifestyle, self-perceived eye health and general health. Enrolment of participants began in April 2022. PERSPECTIVE: The FOREVERdb is a powerful tool to answer a wide range of research questions that can pave the way for better eye health. This database will provide valuable insights for future studies investigating the correlations between eye and general health in a Danish population cohort, enabling research to identify potential risk factors for a range of diseases.

Preoperative Positioning and Progression of Fovea-on Retinal Detachments.

PURPOSE: To study the relationship between positioning and rhegmatogenous retinal detachment (RRD) progression before surgery in patients with a fovea-on RRD. DESIGN: Prospective, single-cohort study. SUBJECTS: Patients with fovea-on RRD admitted to hospital for bedrest before surgical treatment were recruited. METHODS: Primary outcome was the shortest distance from the foveal center to the retinal detachment border on OCT. Secondary outcomes were measured with a head-mounted positioning sensor and included measures of head movement (linear acceleration and angular velocity) as well as measures of positioning regimen compliance. MAIN OUTCOME MEASURES: Distance from the fovea to the retinal detachment border. RESULTS: Overall, 50 patients with fovea-on positioned before RRD repair. One patient (1/50, 2%) progressed from fovea-on to fovea-off. Of the positioning measures, angular velocity demonstrated the strongest correlation with RRD border movement, whereas measures of positioning compliance showed nonsignificant correlation. After defining 3 movement groups: stable, intermediate, and mobile RRDs, we found that a doubling of head movement (angular velocity) correlated with a median RRD border progression of -6 µm/h, -75 µm/h, and -219 µm/h in the 3 groups, respectively. CONCLUSIONS: Rhegmatogenous retinal detachment border movement is correlated to angular velocity of the head, whereas compliance with our current positioning regimen does not have a significant impact on RRD border movement. Not all RRDs progress rapidly toward the fovea, but those that do seem to be highly influenced by head movement. For limiting RRD progression, a reduced movement positioning regimen may be superior to our current gravity-based approach. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

A validated test has been developed for assessment of manual small incision cataract surgery skills using virtual reality simulation.

This study investigates the validity evidence of metrics used for the assessment of surgical skills for Manual Small Incision Cataract Surgery (MSICS) in a virtual reality simulator. MSICS surgery is a low-cost, low-technology cataract surgery technique, which is widely used in low- and middle-income countries. However, there is a lack of cataract surgeons globally, and efficient and evidence-based training of new surgeons is needed. In order to investigate the validity of simulator metrics, we included three groups of participants: (1) MSICS novices who were ophthalmologists with no cataract surgery experience, (2) MSICS novices who were experienced phacoemulsification cataract surgeons, but with no MSICS experience, and (3) experienced phacoemulsification and MSICS surgeons. The evaluation included 11 steps of the MSICS procedure, and all simulator metrics for those steps were reviewed. Of the 55 initial metrics, 30 showed high positive discriminative ability. A test passing score of 20 out of 30 was established, and one of 15 novices with no MSICS experience (mean score 15.5) and 7 out of 10 experienced MSICS surgeons (mean score 22.7) passed the test. We have developed and established validity evidence for a test for MSICS skills in a virtual reality simulator for future use in proficiency-based training and evidence-based testing of training interventions.

Anti-VEGF Treatment of Diabetic Macular Edema in Denmark: Incidence, Burden of Therapy, and Forecasting Analyses.

BACKGROUND: The aim of this study was to analyze demographically stratified incidence rates of patients with diabetic macular edema (DME) commenced in anti-VEGF therapy, to study temporal trends, to report the proportion of patients in active therapy over time, and to develop a model to forecast the future number of patients in active treatment. METHODS: This was a retrospective registry-based study of all patients with DME who received at least one intravitreal anti-VEGF treatment from 1 January 2007 to 30 June 2022. Population data were extracted from Statistics Denmark. RESULTS: This study included 2220 patients with DME who were commenced in anti-VEGF therapy. Demographic analyses revealed higher incidence rates among males than females and among those aged 60-80 years. The number of patients in active treatment followed an exponential decay curve; hence, this was used to mathematically model the number of patients in active therapy. The number of patients in active treatment is expected to stay relatively stable with a minimal increase until the year 2023. CONCLUSIONS: This study provides insight into the practical aspects of the anti-VEGF treatment of DME that allow the planning of adequate health services.

Bidirectional 5-year risks of diabetic retinopathy, glaucoma and/or ocular hypertension: Results from a national screening programme.

PURPOSE: We aimed to investigate if diabetic retinopathy (DR), glaucoma and/or ocular hypertension (OHT) are prospectively linked, as previous studies have proposed cross-sectional associations, but longitudinal data from larger cohorts are lacking. METHODS: We performed a bidirectional 5 years prospective, registry-based cohort study. We extracted data from national registers, including the Danish Registry of Diabetic Retinopathy, the Danish Civil Registration System, the Danish National Patient Register and the Danish National Prescription Registry. DR level was defined by the highest level of the two eyes. Glaucoma and/or OHT was defined by diagnostic codes (H40*) or at least three redeemed prescriptions of glaucoma medication (S01E*) within 1 year. We included 205 970 persons with diabetes and 1 003 170 age- and gender-matched non-diabetes controls. Exposures were level-specific DR (i) and glaucoma and/or OHT (ii), and outcomes were hazard ratios (HRs) for 5 years incident glaucoma and/or OHT (i) and DR (ii). RESULTS: Persons with diabetes were more likely to develop glaucoma and/or OHT (multivariable adjusted HR 1.11, 95% CI 1.06-1.15), but this did not depend on the level of DR. In persons with diabetes, those with glaucoma and/or OHT were more likely to develop DR (multivariable adjusted HR 1.12, 95% CI 1.03-1.23) within 5 years. CONCLUSION: In a national cohort, diabetes associated with a little higher risk of upcoming glaucoma and/or OHT, and, inversely, the presence of the latter predicted a higher risk of incident DR. Nevertheless, our data do not seem to justify including glaucoma evaluation in the national Danish DR-screening programme.

Longitudinal analysis of health care costs in patients with childhood onset inherited retinal dystrophies compared to healthy controls.

BACKGROUND: We evaluated health care costs in patients with childhood onset visual impairment caused by inherited retinal dystrophies (IRD). METHODS: The IRD cohort, identified from the Danish Registry of Blind and Partially Sighted Children, was compared to age- and sex-matched controls from the national, Danish population registry. Information on health care expenditures for somatic and psychiatric in- and outpatient services, purchase of prescription medications and paid assistance at home were obtained from national registries for the years 2002-2017. RESULTS: We included 412 in the IRD cohort (6,290 person years) and 1656 (25,088 person years) in the control cohort. Average, annual health care expenditures from age 0-48 years of age were €1,488 (SD 4,711) in the IRD cohort and €1,030 (4,639) in the control cohort. The largest difference was for out-patient eye care (13.26 times greater, 95% confidence interval 12.90-13.64). Psychiatric in-patient expenditures were 1.71 times greater (95% CI 1.66-1.76) in the IRD cohort but psychiatric out-patient health care costs were comparable between groups. CONCLUSIONS: Health care costs were approximately 40% greater in the IRD cohort compared to an age- and sex-matched sample from the general Danish population. This is relevant in the current situation with a number of trials aimed at treating IRDs using genetically based therapies. Although eye care expenditures were many times greater, they made up < 10% of the total health care expenditures even in the IRD cohort. The reduced costs related to injuries in the visually impaired cohort was a surprising finding but may reflect a reduced propensity to seek medical care rather than a reduced risk of injuries.

Childhood-onset retinal dystrophies reduces life-time income by one third - an individual based socio-economic analysis.

BACKGROUND: The aim of this study was to evaluate lifetime income, educational level and workforce participation in patients with childhood-onset inherited retinal dystrophies (IRD). MATERIAL AND METHODS: The registry-based study using national, Danish databases on education, income, employment and social benefits in a cohort of 515 patients with childhood-onset IRD and without severe systemic comorbidities matched 1:4 to an age- and sex to a control sample of the Danish background population. Socio-economic status was modelled with focus on grade mark points after primary education, highest attained education at 30 years or age, employment and unemployment rate, disability pension and lifetime income. RESULTS: At 30 years of age, the proportion of those who had primary education as the highest achieved level was higher in the IRD group (35.4% versus 18.7%) and they were more likely to be receiving a disability pension (OR 11.77) or be unemployed (OR 6.63). Those at work had the same number of work hours as the control group, and the same proportion had obtained a Master or PhD degree (14%). At 30 years of age, income earnings were lower in the IRD group and the lifetime income was reduced by 30%. CONCLUSION: A few among those with childhood-onset IRD were able to obtain high educational levels, and many were assigned a disability pension from early adulthood or were unemployed, resulting in a markedly reduced lifetime income although grade mark points from primary education were comparable, suggesting that the difference was not explained by intellectual differences between the groups.

Automated artificial intelligence-based system for clinical follow-up of patients with age-related macular degeneration.

PURPOSE: In this study, we investigate the potential of a novel artificial intelligence-based system for autonomous follow-up of patients treated for neovascular age-related macular degeneration (AMD). METHODS: A temporal deep learning model was trained on a data set of 84 489 optical coherence tomography scans from AMD patients to recognize disease activity, and its performance was compared with a published non-temporal model trained on the same data (Acta Ophthalmol, 2021). An autonomous follow-up system was created by augmenting the AI model with deterministic logic to suggest treatment according to the observe-and-plan regimen. To validate the AI-based system, a data set comprising clinical decisions and imaging data from 200 follow-up consultations was collected prospectively. In each case, both the autonomous AI decision and original clinical decision were compared with an expert panel consensus. RESULTS: The temporal AI model proved superior at detecting disease activity compared with the model without temporal input (area under the curve 0.900 (95% CI 0.894-0.906) and 0.857 (95% CI 0.846-0.867) respectively). The AI-based follow-up system could make an autonomous decision in 73% of the cases, 91.8% of which were in agreement with expert consensus. This was on par with the 87.7% agreement rate between decisions made in the clinic and expert consensus (p = 0.33). CONCLUSIONS: The proposed autonomous follow-up system was shown to be safe and compliant with expert consensus on par with clinical practice. The system could in the future ease the pressure on public ophthalmology services from an increasing number of AMD patients.

Diabetic Retinopathy Predicts Risk of Alzheimer's Disease: A Danish Registry-Based Nationwide Cohort Study.

BACKGROUND: Retinal neurodegeneration is evident in early diabetic retinopathy (DR) which may be associated with other neurodegenerative diseases like Alzheimer's disease (AD). OBJECTIVE: To investigate diabetes and DR as a risk marker of present and incident AD. METHODS: A register-based cohort study was performed. We included 134,327 persons with diabetes above 60 years of age, who had attended DR screening, and 651,936 age- and gender-matched persons without diabetes. RESULTS: At baseline, the prevalence of AD was 0.7% and 1.3% among patients with and without diabetes, respectively. In a multivariable regression model, patients with diabetes were less likely to have AD at baseline (adjusted OR 0.63, 95% CI 0.59-0.68). During follow-up, incident AD was registered for 1473 (0.35%) and 6,899 (0.34%) persons with and without diabetes, respectively. Compared to persons without diabetes, persons with diabetes and no DR had a lower risk to develop AD (adjusted HR 0.87, 95% CI 0.81-0.93), while persons with diabetes and DR had higher risk of AD (adjusted HR 1.24, 95% CI 1.08-1.43). When persons with diabetes and no DR were used as references, a higher risk of incident AD was observed in persons with DR (adjusted HR 1.34, 95% CI 1.18-1.53). CONCLUSION: Individuals with diabetes without DR were less likely to develop AD compared to persons without diabetes. However, individuals with DR had a 34% higher risk of incident AD, which raise the question whether screening for cognitive impairment should be done among individuals with DR.

Quantifying surgical skill in macular surgery.

PURPOSE: To evaluate the relationship between patient outcome and surgical experience by developing an objective quality measure of macular hole surgery based on forceps damage to the inner retina. METHODS: We retrospectively examined 3 macular hole case series >1 year after pars plana vitrectomy, internal limiting membrane peeling and gas tamponade. The patients were operated by (1) a novice surgeon (<20 cases), (2) an intermediate (150+ cases) and (3) an experienced surgeon (2000+ cases). Primary outcome was inner retinal volume defect as segmented from optical coherence tomography (GCL++: thickness from internal limiting membrane to inner plexiform layer). Secondary outcome was retinal function measured by confocal microperimetry using a custom scanning protocol. RESULTS: Thirty-two patients were examined: 11, 10 and 11 patients in the novice, intermediate and experienced surgeon group, respectively. Median GCL++ volume defect was 23.68 × 106 µm3 (IQR: 22.77 × 106 -44.81 × 106 µm3 ), 8.42 × 106 µm3 (IQR: 4.86 × 106 -10.03 × 106 µm3 ) and 3.55 × 106 µm3 (IQR: 1.44 × 103 -7.94 × 106 µm3 ) in the novice, intermediate and experienced surgeon group, respectively (p = 0.0004). The novice surgeon volume defect differed significantly from the intermediate and experienced surgeon (p = 0.016 and p = 0.0002, respectively). A subset of 12 patients underwent microperimetry measurements demonstrating correlation between inner retinal volume defect and reduced retinal sensitivity (p = 0.02). CONCLUSIONS: Forceps induced inner retinal damage commonly occurs during initiation of internal limiting membrane peeling in macular hole surgery. Damage to the structure and function of the inner retina seems to correlate to surgical experience.

The risk for developing vision-threatening retinopathy after cataract surgery in diabetic patients depends on the postoperative follow-up time.

PURPOSE: To identify parameters that can predict the postoperative risk for progression of retinopathy to a vision-threatening stage after cataract surgery. This may optimize the timing of surgery and the postoperative follow-up strategy in diabetic patients. METHODS: Multi-state survival analysis with death as competing risk was used to investigate how year of onset and age of onset of diabetes, gender, body mass index, HbA1c and blood pressure had affected the risk for developing diabetic macular oedema (DME) and proliferative diabetic retinopathy (PDR) among 2540 right eyes from 2797 diabetic patients operated for cataract on one or both eyes during 25 years until July 1. 2019. RESULTS: Cataract surgery had been performed in 98.8% of patients reaching 90 years of age. The risk for developing both DME and PDR was increased by cataract surgery. The risk was highest during the first postoperative years and increased by pre-operative variability in HbA1c. The risk after more than 20 years postoperatively increased by increased cumulative HbA1c pre-operatively. The other studied risk factors contributed differently to the development of the two complications. CONCLUSIONS: Decision models for the timing of cataract surgery in diabetic patients should consider that the risk for developing vision-threatening retinopathy depends on follow-up time. Differences in the risk profiles for developing DME and PDR after cataract surgery support that the two complications should be regarded as separate late complications.

Detection of oedema on optical coherence tomography images using deep learning model trained on noisy clinical data.

PURPOSE: To meet the demands imposed by the continuing growth of the Age-related macular degeneration (AMD) patient population, automation of follow-ups by detecting retinal oedema using deep learning might be a viable approach. However, preparing and labelling data for training is time consuming. In this study, we investigate the feasibility of training a convolutional neural network (CNN) to accurately detect retinal oedema on optical coherence tomography (OCT) images of AMD patients with labels derived directly from clinical treatment decisions, without extensive preprocessing or relabelling. METHODS: A total of 50 439 OCT images with associated treatment information were retrieved from databases at the Department of Ophthalmology, Rigshospitalet, Copenhagen, Denmark between 01.06.2007 and 01.06.2018. A CNN was trained on the retrieved data with the recorded treatment decisions as labels and validated on a subset of the data relabelled by three ophthalmologists to denote presence of oedema. RESULTS: Moderate inter-grader agreement on presence of oedema in the relabelled data was found (76.4%). Despite different training and validation labels, the CNN performed on par with inter-grader agreement in detecting oedema on OCT images (AUC 0.97, accuracy 90.9%) and previously published models based on relabelled datasets. CONCLUSION: The level of performance shown by the current model might make it valuable in detecting disease activity in automated AMD patient follow-up systems. Our approach demonstrates that high accuracy is not necessarily constrained by incongruent training and validation labels. These results might encourage the use of existing clinical databases for development of deep learning based algorithms without labour-intensive preprocessing in the future.

In Vivo Labeling and Tracking of Proliferating Corneal Endothelial Cells by 5-Ethynyl-2'-Deoxyuridine in Rabbits.

Purpose: To develop a method to label proliferating corneal endothelial cells (ECs) in rabbits in vivo and track their migration over time. Methods: We compared intraperitoneal (IP) and intracameral (IC) administration of 5-ethynyl-2'-deoxyuridine (EdU) in two experiments: (1) six rabbits received IP or IC EdU. Blood and aqueous humor (AH) samples were incubated with HL-60 cells. Flow cytometry detected the EdU incorporation, representing the bioavailability of EdU. (2) In vivo EdU labeling was investigated in pulse-chase study: 48 rabbits received EdU IP or IC. The corneas were flat-mounted after 1, 2, 5, or 40 days and imaged using fluorescence microscopy. EdU+ and Ki67+ ECs were quantified and their distance from the peripheral endothelial edge was measured. Results: EdU was bioavailable in the AH up to 4 hours after IC injection. No EdU was detected in the blood or the AH after IP injection. High quality EdU labeling of EC was obtained only after IC injection, achieving 2047 ± 702 labeled ECs. Proliferating ECs were located exclusively in the periphery within 1458 ± 146 µm from the endothelial edge. After 40 days, 1490 ± 397 label-retaining ECs (LRCs) were detected, reaching 2219 ± 141 µm from the edge, indicating that LRCs migrated centripetally. Conclusions: IC EdU injection enables the labeling and tracking of proliferating ECs. LRCs seem to be involved in endothelial homeostasis, yet it remains to be investigated whether they represent endothelial progenitor cells. Translational Relevance: EdU labeling in animal models can aid the search for progenitor cells and the development of cell therapy for corneal endothelial dysfunction.

Subretinal Saline Protects the Neuroretina From Thermic Damage During Laser Induction of Experimental Choroidal Neovascularization in Pigs.

Purpose: The purpose of this study was to develop a porcine model for photocoagulation induced choroidal neovascularization (CNV) with high success rate and minimal thermic damage to the neuroretina. Methods: Experimental CNV was induced by laser photocoagulation in both eyes of 16 domestic pigs. In the left eyes, photocoagulation was preceded by subretinal injection of saline to protect the neuroretina from thermic damage, whereas the right eyes were treated with photocoagulation only. The development of the CNV after 3, 7, 14, 28, and 42 days was evaluated by optical coherence tomography (OCT) scanning, fluorescein angiography, and OCT angiography, and by histology after enucleation. Results: From day 7 after the photocoagulation, OCT showed subretinal density in all lesions of 14 alive animals, and either fluorescein or OCT angiography confirmed CNV formation in 11 of 14 of the eyes that had received photocoagulation alone and those in which photocoagulation had been preceded by subretinal injection of saline. In all cases pretreated with subretinal saline, the neuroretina was protected from immediate thermic damage. The formation of CNVs were confirmed by histology. For both groups, the largest lesions were observed within 14 days after photocoagulation. Conclusions: Injection of subretinal saline can protect the retina from thermic damage induced by retinal photocoagulation without reducing the success rate in producing experimental CNV. The effect of interventional studies aimed at reducing photocoagulation induced experimental CNV in pigs can be evaluated within 2 weeks after photocoagulation. Translational Relevance: This model provides a fundament to develop and evaluate novel treatment methods for neovascular retinal diseases.

Comparing corneal outcome between femtosecond laser-assisted cataract surgery and conventional phaco surgery in Fuchs' endothelial dystrophy patients: a randomized pilot study with 6mo follow up.

AIM: To compare the corneal outcome in Fuchs' endothelial dystrophy (FED) patients between femtosecond laser-assisted cataract surgery (FLACS) and conventional phaco surgery (CPS). METHODS: This was a randomized controlled study comparing one eye surgery by FLACS and the contralateral eye operated by CPS (stop and chop technique) in FED patients. Central corneal thickness, corneal light backscatter, corneal densitometry, and central corneal endothelial cell count and hexagonality (noncontact endothelial cell microscope), and corrected distance visual acuity (CDVA) were assessed preoperatively and at day 1, 40, and 180 postoperatively. RESULTS: Totally 31 patients (16 women) were included. At day 40 postoperatively, the mean endothelial cell loss (ECL) was 23.67% by FLACS and 17.30% by CPS (P=0.53). At day 180 postoperatively, ECL was 25.58% in FLACS and 21.32% in CPS (P=0.69). Densitometry data in all layers and all annuli from anterior layer to posterior layer in annuli 0-2, 2-6, 6-10 and 10-12, total densitometry with all layers and all annuli was performed. A significant difference was found in 6-10 (posterior layer) at day 1 with -1.42 grayscale units (GSU; 95%CI: -2.66 to -0.19, P=0.02). In 10-12 (anterior layer, central layer and all layers) at day 40 were significant different with 7.7 (95%CI: 1.89 to 13.50, P=0.009), 3.97 (95%CI: 0.23 to 7.71, P=0.03), 4.73 GSU (95%CI: 0.71 to 8.75, P=0.02), respectively. In the remaining parameters we found no difference between the two groups (P>0.05). Three CPS eyes suffered from corneal decompensation. CONCLUSION: There is no significant difference in corneal outcome between FLACS and CPS. Endothelial cell density and pentacam corneal outcome may be inadequate as outcome parameters in FED patients.

The learning curve of robot-assisted vitreoretinal surgery - A randomized trial in a simulated setting.

PURPOSE: To investigate the learning curve of robot-assisted vitreoretinal surgery compared to manual surgery in a simulated setting. METHODS: The study was designed as a randomized controlled longitudinal study. Eight ophthalmic trainees in the 1st or 2nd year of their specialization were included. The participants were randomized to either manual or robot-assisted surgery. Participants completed repetitions of a test consisting of three vitreoretinal modules on the Eyesi virtual reality simulator. The primary outcome measure was time to learning curve plateau (minutes) for total test score. The secondary outcome measures were instrument movement (mm), tissue treatment (mm2 ) and time with instruments inserted (seconds). RESULTS: There was no significant difference in time to learning curve plateau for robot-assisted vitreoretinal surgery compared to manual. Robot-assisted vitreoretinal surgery was associated with less instrument movements (i.e. improved precision), -0.91 standard deviation (SD) units (p < 0.001). Furthermore, robot-assisted vitreoretinal surgery was associated with less tissue damage when compared to manual surgery, -0.94 SD units (p = 0.002). Lastly, robot-assisted vitreoretinal surgery was slower than manual surgery, 0.93 SD units (p < 0.001). CONCLUSIONS: There was no significant difference between the lengths of the learning curves for robot-assisted vitreoretinal surgery compared to manual surgery. Robot-assisted vitreoretinal surgery was more precise, associated with less tissue damage, and slower.

Modelling and prognostication of growth in the number of patients treated for neovascular age-related macular degeneration.

PURPOSE: The number of patients receiving anti-VEGF therapy has increased rapidly since its introduction in Denmark in 2007, placing an enormous pressure on the public healthcare system. In this study, we attempt to describe this growth and identify the factors driving it. METHODS: Data on treatment of the entire population of neovascular AMD patients in the Capital Region of Denmark between 2007 and 2019 was retrieved. The age and sex standardized incidences of first time treatment and changes in duration of treatment were analysed. RESULTS: The number of patients in active treatment increased from 576 in 2007 to 3684 in 2019. The growth was initially driven by accumulation of patients continuing anti-VEGF therapy for extended periods of time (259 patients/year). As larger numbers of patients began to be discharged, the increase slowed to 181 patients/year in late 2010s, with demographic change becoming the main growth driving factor. The incidence of first treatment increased slightly during the study period, mainly for individuals over 85 years. For patients under 85 years, treatment incidences closely followed neovascular AMD incidences from population studies. The likelihood of remaining in anti-VEGF treatment after the initial injection followed exponential decay curve (t1/2 = 3.6 years). Based on this observation, a model was created to describe the number of patients in active treatment, which accurately described historical data (R2 = 0.999), and forecast a linear growth of 138 patients/year until 2030. CONCLUSION: Treatment incidences and modelling reported in this study might facilitate a more informed and accurate planning of future ophthalmology services.