Endophthalmitis following same-day bilateral anti-VEGF injections: a systematic review.

PURPOSE: To review the risk of endophthalmitis in same-day bilateral anti-VEGF injections. METHODS: We searched 12 literature databases for studies on the risk of endophthalmitis after same-day bilateral intravitreal anti-VEGF injections. Data extraction was made independently by two authors and discussed afterward until reaching consensus. RESULTS: Seventeen studies were included with a total of 138,478 intravitreal anti-VEGF injections (69,239 bilateral injections sessions) given in at least 7579 patients. In total, 33 cases of endophthalmitis had occurred, and no cases were bilateral. The incidence of endophthalmitis ranged from 0 to 0.53% per intravitreal injection across studies. CONCLUSIONS: We suggest that clinicians can consider same-day treatment of both eyes of patients in need of bilateral intravitreal anti-VEGF injection therapy, but larger studies are needed to quantify the exact risk of endophthalmitis.

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.

Bariatric surgery in individuals with type 2 diabetes is not associated with short or long-term risk of diabetic retinopathy progression: results from a nationwide cohort study.

AIMS: Bariatric surgery is used to induce weight loss and glycemic stability in type 2 diabetes (T2D). It has been a concern that this may lead to early worsening of diabetic retinopathy (DR) due to a rapid decline in HbA1c. In this study, we evaluated the risk of short and long-term DR development and need for ocular intervention in an entire nation of individuals with T2D undergoing bariatric surgery. METHODS: The study comprised a national, register-based cohort of individuals with T2D screened for DR. Cases were matched by age, sex and DR level at the date of surgery (index date) with non-bariatric controls. We extracted information on DR levels, in- and outpatient treatments, pharmaceutical prescriptions and laboratory values. We evaluated worsening of DR (incident and progressive DR) at follow-up (6 and 36 months). RESULTS: Amongst 238,967 individuals with T2D, who attended diabetic eye screening, we identified 553 that underwent bariatric surgery (0.2%) and 2677 non-bariatric controls. Median age was 49 years, and 63% were female. Cases had more comorbidities, lower HbA1c as well as more frequent use of glucose-lowering and antihypertensive medication than controls at index date. In a fully adjusted logistic regression model, the risk of DR worsening for cases was not significantly different compared to controls, neither short-term (OR 0.41 [CI 95% 0.13; 1.33], p = 0.14) nor long-term (OR 0.64 [CI 95% 0.33; 1.24], p = 0.18). CONCLUSIONS: In this nationwide study, bariatric surgery did not associate with increased risk of short- or long-term DR worsening.

Inter-grader reliability in the Danish screening programme for diabetic retinopathy.

PURPOSE: The Danish Registry of Diabetic Retinopathy includes information from >200 000 patients who attends diabetic retinopathy (DR) screening in Denmark. Screening of patients with uncomplicated type 2 diabetes is often performed by practicing ophthalmologists, while patients with type 1 and complicated type 2 diabetes attends screening at hospitals. We performed a clinical reliability study of retinal images from Danish screening facilities to explore the inter-grader agreement between the primary screening ophthalmologist and a blinded, certified grader. METHODS: Invitations to participate were sent to screening facilities across Denmark. The primary grader uploaded fundus photographs with information on estimated level of DR (International Clinical Diabetic Retinopathy scale as 0 [no DR], 1-3 [mild, moderate or severe nonproliferative DR {NPDR}], or 4 [proliferative DR {PDR}]), region of screening, image style, and screening facility. Images were then regraded by a blinded, certified, secondary grader. Weighted kappa analysis was performed to evaluate agreement. RESULTS: Fundus photographs from 230 patients (458 eyes) were received from practicing ophthalmologists (52.6%) and hospital-based grading centres (47.4%) from all Danish regions. Reported levels of DR by the primary graders were 66.8%, 12.2%, 13.1%, 1.3% and 5.5% for DR levels 0-4. The overall agreement between primary and secondary graders was 93% (κ = 0.83). Based on screening facility agreement was 96% (κ = 0.89) and 90% (κ = 0.76) for practicing ophthalmologists and hospital-based graders. CONCLUSION: In this nationwide study, we observed a high overall inter-grader agreement and based on this, it is reasonable to assume that reported DR gradings in the screening programme in Denmark, accurately reflect the truth.

Prevalence and severity of diabetic retinopathy in pregnant women with diabetes-time to individualize photo screening frequency.

AIMS: To evaluate the prevalence and severity of diabetic retinopathy including macular oedema in pregnant women with diabetes and to identify women in whom the frequency of retinal screening can be reduced to minimize the burden of health care visits. METHODS: A cohort study of 348 women with pre-existing diabetes were routinely screened with retinal photo in early (12 weeks) and late pregnancy (27 weeks). Diabetic retinopathy was classified in five stages in accordance with National Danish Guidelines based on the eye with the highest retinopathy level. Sight-threatening retinopathy was defined as the presence of proliferative retinopathy and/or clinically significant macular oedema (CSMO). RESULTS: Retinopathy was present in 52% (116/223) vs. 14% (17/125), with sight-threatening retinopathy in 16% (35/223) vs. 6% (7/125) of women with type 1 and type 2, respectively. Women without retinopathy in early and late pregnancy were characterized by shorter diabetes duration (p < 0.0001 and p = 0.008) and predominance of type 2 diabetes. Amongst the 50% (175/348) of the cohort having no retinopathy in early pregnancy and HbA1c<53 mmol/mol (7.0%), none developed sight-threatening retinopathy and 94% (165/175) remained without any retinopathy during pregnancy. Development of sight-threatening retinopathy was mainly observed in women with retinopathy in early pregnancy. Treatment for sight-threatening retinopathy was given to a minority (2.7 and 2.4%, respectively). CONCLUSION: Good glycaemic control and no retinopathy was seen in a large proportion of women in early pregnancy and none of these women developed sight-threatening retinopathy. The frequency of retinal screening can probably be safely reduced during pregnancy in these women.

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.

Quality assessment of a screening algorithm for diabetic retinopathy: prolongation of screening intervals with minimal effect of HbA1c and arterial hypertension on the length of intervals.

PURPOSE: At Steno Diabetes Center Copenhagen (SDCC), diabetic retinopathy (DR) screening intervals are based on quantification of retinal lesions. Screening intervals are, for the milder forms of DR, prolonged to 2-3 years. The purpose of the present study was to evaluate the effect of the prolongation on developing unexpected events and to evaluate the effect of HbA1c and arterial hypertension. METHODS: We assessed 18 972 screening intervals from 6000 patients from 1/1-2003 to 1/5-2017 for occurrence of unexpected events, defined as: (1) DR progression requiring treatment, at the following screening date, and (2) DR-related hospital contact within the planned interval. We modelled the effect of several risk factors for developing unexpected events in a Cox regression. Furthermore, we assessed the risk of unexpected events in a logistic regression analysis using cubic splines to model the effect of HbA1c , stratified by arterial hypertension status. RESULTS: 16 283 (86%) intervals followed the planned interval and among those, only 86 (0.5%) experienced unexpected events. Intervals of dysregulated patients (86% of all intervals) did not experience more unexpected events, compared with well-regulated patient intervals (Hazard Ratio: 1.12, 95% CI: 0.55-2.27). We found a nonlinear effect of HbA1c on the risk of unexpected events which peaked around HbA1c levels of 80 mmol/mol. Having arterial hypertension slightly increased the risk of unexpected events. CONCLUSIONS: The present study supports the validity of the current algorithm. We found no increased risk of unexpected events among dysregulated intervals but a nonlinear effect of HbA1c . Age, diabetes duration and diabetes type were significantly associated with unexpected events.

Optimizing the treatment of rhegmatogenous retinal detachment.

Surgical approaches for rhegmatogenous retinal detachment (RRD) have evolved rapidly in the past century. This has resulted in an increase in the anatomical success rate from zero per cent in the beginning of the 1900s to now almost 100 per cent. Rhegmatogenous retinal detachment is regarded as an acute eye disease that needs immediate treatment. With the increasing number of cataract surgeries and an increased elderly population, the numbers of RRD occurrences are increasing. The aim of this thesis is to create knowledge on how treatment and care of RRD patients can be optimized. In the first paper, data on the incidence of RRD in Denmark are presented based on data from a nation register the National Patient Registry (NPR). It was discovered that the incidence of RRD in Denmark is similar to previous reported numbers and that the incidence has been increasing due to increasing numbers of cataract surgeries and an increased elderly population. Using data from the NPR, we estimated that the risk of a RRD occurring on the fellow eye is 100 times larger than on the first eye and that middle aged men have the highest risk. Having an increase in the incidence of RRD we need to ensure that the patients are also treated in the most optimal way. To ensure this, an indicator is needed to monitor the quality at the different centres. This indicator presented in the second paper is based in the occurrence of redetachment. We define a detachment to be caused by poor surgery if the retina detaches within one year after initial surgery with pneumatic retinopexy, scleral buckling and VTX with gas, and one and a half years after surgery with VTX with oil. Also lack of oil removal within the first year is a failed operation. It is widely accepted that RRD is an acute disease but when should surgery be performed to attain the most optimal result? In the third paper, we evaluated the progression of posterior RRD with an optical coherence tomography to make an objective assessment of the movement. We found that the risk of a macula on RRD progressing to affect the fovea is small if the patient is postured appropriately. We found that the movement of the RRD is dynamic but the detachments will ultimately approach the fovea. Having an opportunity to postpone surgery without risking the outcome for the patient allows a more optimal surgery. The results of this thesis can be used by all health care systems to establish optimal conditions in the treatment of RRD.

Reoperation for rhegmatogenous retinal detachment as quality indicator for disease management: a register study.

PURPOSE: To establish a quality indicator that could be used in optimizing treatment for rhegmatogenous retinal detachment (RRD). METHODS: The Danish National Patient Registry was used to identify surgery conducted in Denmark for RRD in the period 01 January 2001-31 December 2009. Cases were identified by diagnosis and surgical codes. RESULTS: A total of 6522 cases were operated for a primary RRD in the study period, and 22% (1434 patients) were reoperated for a redetachment. A Cox regression analysis showed that the risk of redetachment was equal to or less than detachment on the fellow eye 1 year after primary surgery with techniques not using silicone oil. The same was true 1.5 years after surgery for techniques using silicone oil. Based on this, we established a quality indicator defining failure as the need for operation for redetachment within 1 year from initial surgery when using techniques without oil and after 1.5 years for techniques using oil. Also the lack of oil removal within 1 year from initial surgery should be noted as an operational failure. We applied the quality indicators on the cohort of 6522 RRDs and found that in Denmark the need for redetachment surgery has decreased over time and also that high-volume departments have better outcome compared to smaller ones. CONCLUSIONS: The risk of reoperation for redetachment after initial surgery fulfils the criteria for a good quality indicator and can be used in RRD surgery. This indicator could aid in optimizing the management of RRD patients to minimize morbidity.

A nationwide study on the incidence of rhegmatogenous retinal detachment in Denmark, with emphasis on the risk of the fellow eye.

PURPOSE: To estimate the risk of developing rhegmatogenous retinal detachment (RRD) in the fellow eye in patients with RRD in the first eye and to identify potential risk factors. METHODS: We used the Danish National Patient Registry to identify all surgeries performed for RRD in Denmark in the period from January 2000 to July 2011. RESULTS: In 11,451 cases of RRD in the study period, 8,553 cases in 8,081 patients were identified as primary RRD with an annual incidence of 13.7 per 100,000 citizens. There was a significant increase in the number of cases with RRD during the study period that was mainly explained by an increase of cataract surgeries. Four hundred and seventy-one of 7,941 patients with primary RRD on one eye and no other previous eye disease developed an additional RRD in the fellow eye with an overall incidence of 1% per year. Cox analysis revealed male gender, surgery on the lens, and young age as significant risk factors (P < 0.0001). CONCLUSION: Patients with RRD on the first eye have a 100 times greater risk of developing RRD on the second eye, and the risk increases with male gender and surgery on the lens but decreases with age.

Progression of foveola-on rhegmatogenous retinal detachment.

AIMS: Quantitative assessment of the rate of progression of recent onset posterior rhegmatogenous retinal detachment (RRD). METHODS: A prospective observational study on patients presenting with acute symptomatic primary foveola-on RRD over a 32-month period. Patients were evaluated with optical coherence tomography (OCT) to confirm foveola status. A total of 96 eyes were enrolled and 50 were eligible for quantitative measurement of the movement of the detachment by OCT. RESULTS: Only one eye progressed from foveola-on to foveola-off in the 96 evaluated eyes. In seven of the 50 eyes eligible for quantitative measurement, the detachment was stable during admission. In all others, the movement was very dynamic with episodes of progression and regression. We found that 18% (9/50) of the detachments had a net movement towards foveola during admission. Logistic regression established the amount of time admitted (OR=1.05, p=0.027) as significant risk factor for progression. CONCLUSIONS: The risk of progression of a foveola-on RRD to affect the fovea is small the first night of admission (1%). The amount of time surgery is delayed was found as significant risk factor for progression towards foveola.