Risk of post-injection endophthalmitis peaks within the first three injections of anti-vascular endothelial growth factor therapy: A nationwide registry-based study.

PURPOSE: To report the incidence of post-injection endophthalmitis (PIE) and the cumulative risk associated with repeated injections of intravitreal anti-vascular endothelial growth factor (anti-VEGF). METHODS: We employed nationwide registries in Denmark to include all individuals aged ≥40 years who received at least one intravitreal anti-VEGF injection in 2007-2022. Our primary endpoint PIE was identified using specific diagnostic codes for endophthalmitis and procedure codes for vitreous biopsy within 10 days prior to and 120 days post-injection. Patients were stratified according to the underlying diagnoses for which they received the treatment. The relative risk (RR) for PIE was calculated between groups based on the number of injections received by the patients. RESULTS: We identified 60 825 patients who received intravitreal anti-VEGF treatment during study time, with a median age of 77.2 years and females constituting 58.1%. We identified 232 cases of PIE after 1 051 549 injections during follow-up, resulting in an incidence of 0.022% [95% CI 0.019%-0.025%]. Despite a linear growth in annual anti-VEGF use, the incidence remained stable at 0.020% [95% CI 0.017%-0.023%] from 2013 to 2022. Compared to patients receiving 1-3 injections, RR for patients receiving 4-20, 21-40, and >40 injections were 0.46 [95% CI 0.34-0.63], 0.32 [95% CI 0.21-0.50], and 0.54 [95% CI 0.36-0.81], respectively. Findings were similar across the different diagnoses. CONCLUSIONS: Based on 16 years of nationwide registry data, this study identified a low and stable incidence of PIE. Notably, the highest risk of endophthalmitis was within the first three anti-VEGF injections.

The role of phacoemulsification surgery in the incidence rate of rhegmatogenous retinal detachment.

PURPOSE: To investigate changes in the incidence rate of primary rhegmatogenous retinal detachment (RRD) surgery over time and to determine to what extent these changes can be attributed to pseudophakia. METHODS: This nationwide cohort study was based on national patient registries. The study population comprised individuals at risk of RRD aged 40 years and above from 2006 to 2021 in Denmark. The primary outcome was RRD incidence, and the exposure was phacoemulsification surgery. A chart review was conducted to validate and examine the lens status of the outcome. RESULTS: The crude and age-adjusted incidence rate of RRD in the Danish population increased significantly during the study period. The largest increase in RRD was seen in phakic RRD (phRRD) (65%), whereas pseudophakic RRD (pRRD) accounted for 35% of the total increase. A chart review revealed that 17% of phRRDs were misclassified as pseudophakic, resulting in pRRD accounting for a total of 45% of the increase in RRD. The prevalence of pseudophakia in Denmark grew significantly for all age groups and for both sexes (p = 10-6) from 2006 to 2021, but the 1-year incidence of pRRD in the pseudophakic population was constant throughout the entire period. CONCLUSION: The incidence rate of RRD is continuing to increase in Denmark. The increase in phRRD remains undetermined, and while the risk of pRRD seemed to be constant during the study period, 45% of the overall increase in RRD could be attributed to the rise of a growing pseudophakic population.

Central subfield thickness of diabetic macular edema: Correlation with the aqueous humor proteome.

Purpose: Diabetic macular edema (DME) is a sight-threatening complication of diabetes. Consequently, studying the proteome of DME may provide novel insights into underlying molecular mechanisms. Methods: In this study, aqueous humor samples from eyes with treatment-naïve clinically significant DME (n = 13) and age-matched controls (n = 11) were compared with label-free liquid chromatography-tandem mass spectrometry. Additional aqueous humor samples from eyes with treatment-naïve DME (n = 15) and controls (n = 8) were obtained for validation by enzyme-linked immunosorbent assay (ELISA). Best-corrected visual acuity (BCVA) was evaluated, and the severity of DME was measured as central subfield thickness (CST) employing optical coherence tomography. Control samples were obtained before cataract surgery. Significantly changed proteins were identified using a permutation-based calculation, with a false discovery rate of 0.05. A human donor eye with DME and a control eye were used for immunofluorescence. Results: A total of 101 proteins were differentially expressed in the DME. Regulated proteins were involved in complement activation, glycolysis, extracellular matrix interaction, and cholesterol metabolism. The highest-fold change was observed for the fibrinogen alpha chain (fold change = 17.8). Complement components C2, C5, and C8, fibronectin, and hepatocyte growth factor-like protein were increased in DME and correlated with best-corrected visual acuity (BCVA). Ceruloplasmin and complement component C8 correlated with central subfield thickness (CST). Hemopexin, plasma kallikrein, monocyte differentiation antigen CD14 (CD14), and lipopolysaccharide-binding protein (LBP) were upregulated in the DME. LBP was correlated with vascular endothelial growth factor. The increased level of LBP in DME was confirmed using ELISA. The proteins involved in desmosomal integrity, including desmocollin-1 and desmoglein-1, were downregulated in DME and correlated negatively with CST. Immunofluorescence confirmed the extravasation of fibrinogen at the retinal level in the DME. Conclusion: Elevated levels of pro-inflammatory proteins, including the complement components LBP and CD14, were observed in DME. DME was associated with the loss of basal membrane proteins, compromised desmosomal integrity, and perturbation of glycolysis.

Lack of stereopsis does not reduce surgical performance but prolongs the learning curve of vitreoretinal surgery.

PURPOSE: To investigate whether individuals with long-term reduced stereopsis were able to obtain the same level of surgical skills in simulated vitreoretinal surgery on the Eyesi Surgical Simulator as individuals with normal stereopsis. METHODS: Twenty-four medical students were recruited and divided into two groups according to their degree of stereopsis: Group 1 (n = 12) included subjects with normal stereopsis (60 arcsec or lower) and Group 2 (n = 12) included subjects with reduced stereopsis (120 arcsec or higher). Stereopsis was tested using the TNO test (Lameris Ootech BV, Nieuwegein, the Netherlands). The participants were trained in virtual reality-simulated vitreoretinal surgery and continuously measured using a test with solid validity evidence and a pre-defined pass-fail score. All data were analysed using the Wilcoxon rank sum test. RESULTS: We observed no differences in overall performance scores for any of the four modules. The participants with reduced stereopsis used 5.8 more attempts in bimanual training (p = 0.04), 8.8 more attempts in removal of posterior hyaloid (p = 0.04), 9.1 more attempts in navigation training (p = 0.20) and 0.3 fewer attempts in removal of internal limiting membrane (p = 0.69). CONCLUSION: The final performance scores on the Eyesi Surgical Simulator were independent of the degree of stereopsis. However, the number of attempts to achieve the pre-defined pass-fail score increased significantly with reduced stereopsis in two of four modules. These results indicate that a high degree of stereopsis is not necessary to become proficient in microsurgery but may prolong the learning curve.

Retinal vascular structure independently predicts the initial treatment response in neovascular age-related macular degeneration.

PURPOSE: Prediction of the early treatment response is important in neovascular age-related macular degeneration (nAMD). Hence, we aimed to test if non-invasive measurements of the retinal vascular structure were able to predict a successful outcome of initial intravitreal treatment. METHODS: In 58 eyes of 58 patients with treatment-naïve nAMD, advanced markers of retinal vascular structure were measured by Singapore I Vessel Assessment prior to initial intravitreal treatment with three monthly injections of aflibercept with subsequently categorization of patients as full treatment responders (FTR) or non/partial treatment responders (N/PR), with the former defined as loosing fewer than five Early Treatment Diabetic Retinopathy Study letters and having no residual intra- or subretinal fluid or macular haemorrhage. RESULTS: Of 54 eyes attending follow-up, 44.4% were categorized as FTR. Patients with FTR were older (81.5 vs. 77 years, p = 0.04), and prior to treatment those eyes had a lower retinal arteriolar fractal dimension (Fd) (1.21 vs. 1.24 units, p = 0.02) and venular length-diameter ratio (LDR) (7.3 vs. 15.9 units, p = 0.006), but did not differ with respect to other retinal vascular parameters. In multiple logistic regression models, a lower chance of FTR was independently predicted by a higher retinal venular LDR (odds ratio [OR] 0.91, 95% CI 0.82-0.99, p = 0.03, for each 1 unit increment) and marginally by a higher retinal arteriolar Fd (OR 0.83, 95% CI 0.68-1.00, p = 0.05, for each 0.01 unit increment). CONCLUSION: Retinal venular LDR independently predicted the initial treatment response in nAMD. If confirmed by long-term, prospective studies, this might help to guide treatment.

Artificial intelligence within ophthalmologic diseases.

As ophthalmology is an increasingly busy medical specialty relying solidly on imaging technology, this review investigates the introduction of artificial intelligence to improve diagnostic performance and reduce human resources. In diabetic retinopathy screening, algorithms are now regulatory-approved for international markets but not yet tailored for the Danish system. In age-related macular degeneration, algorithms are now able to facilitate the classification and segmentation of disease activity, and in upcoming years, these are likely to assist us to improve diagnosis and provide subsequent clinical care.

Patient perspectives and barriers in the treatment of neovascular age-related macular degeneration in Denmark: a qualitative study.

OBJECTIVES: This qualitative study aims to identify patient-reported barriers to treatment for neovascular age-related macular degeneration (nAMD) and investigate their impact on quality of life. DESIGN: Using a qualitative explorative design. SETTING: Semi-structured individual or dyadic interviews were conducted with patients and their relatives. PARTICIPANTS: Twenty-one patients completed the interview, with four of them having a relative present. INTERVENTIONS: Gadamer's hermeneutics guided the epistemological approach, and maximum variation sampling was employed to capture diverse patient experiences. An advisory board consisting of patients, relatives and ophthalmologists ensured the relevance of the study. Thematic analysis was conducted using NVivo software. PRIMARY AND SECONDARY OUTCOME MEASURES: To investigate patient-reported barriers to the recommended treatment for nAMD and impact on quality of life. RESULTS: The study included 21 patients with nAMD, with a median age of 79 years. Five themes emerged: (1) good compliance with intravitreal treatment, (2) the dual role of relatives, (3) treatment commute, (4) hospital barriers, (5) preventive health literacy. CONCLUSION: This study highlights the resilience and adherence of patients with nAMD in Denmark to their treatment despite various barriers. While the therapy may have negative effects on their well-being, patients do not opt out of treatment. These findings underscore the importance of personalised treatment plans that provide, for example, convenient access to care and clear future agreements at the hospital. By adopting more patient-centred approaches, healthcare providers can enhance patient satisfaction and improve treatment adherence, ultimately leading to better patient outcomes and quality of life.

Intravitreal Vascular Endothelial Growth Factor Inhibitor Therapy in Denmark and 5-Year Projections.

This cohort study examines the use of intravitreal injections of vascular endothelial growth factor inhibitor in Denmark from 2007 through 2022 and forecasts future demand for this 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.

Diagnostic Accuracy of the Amsler Grid Test for Detecting Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-analysis.

Importance: Patients with nonneovascular age-related macular degeneration (AMD) are encouraged to use the Amsler grid test for self-assessment to facilitate early diagnosis. The test is widely recommended, suggesting a belief that it signals worsening AMD, warranting its use in home monitoring. Objective: To systematically review studies of the diagnostic test accuracy of the Amsler grid in the diagnosis of neovascular AMD and to perform diagnostic test accuracy meta-analyses. Data Sources: A systematic literature search was conducted in 12 databases for relevant titles from database inception until May 7, 2022. Study Selection: Studies included those with groups defined as having (1) neovascular AMD and (2) either healthy eyes or eyes with nonneovascular AMD. The index test was the Amsler grid. The reference standard was ophthalmic examination. After removal of obviously irrelevant reports, 2 authors (J.B. and M.S.) independently screened the remaining references in full text for potential eligibility. Disagreements were resolved by a third author (Y.S.). Data Extraction and Synthesis: Two authors (J.B. and I.P.) independently extracted all data and evaluated quality and applicability of eligible studies using the Quality Assessment of Diagnostic Accuracy Studies 2. Disagreements were resolved by a third author (Y.S.). Main Outcomes and Measures: Sensitivity and specificity of the Amsler grid for detecting neovascular AMD with comparators being either healthy control participants or patients with nonneovascular AMD. Results: Of 523 records screened, 10 studies were included with a total of 1890 eyes (mean participant age ranging from 62 to 83 years). Sensitivity and specificity to diagnose neovascular AMD were 67% (95% CI, 51%-79%) and 99% (95% CI, 85%-100%), respectively, when comparators were healthy control participants and 71% (95% CI, 60%-80%) and 63% (95% CI, 49%-51%), respectively, when control participants were patients with nonneovascular AMD. Overall, potential sources of bias were low across studies. Conclusions and Relevance: Although the Amsler grid is easy and inexpensive to use for detection of metamorphopsia, its sensitivity may be at levels typically not recommended for monitoring. Coupling this lower sensitivity with only moderate specificity to identify neovascular AMD in a population at risk, these findings suggest that such patients typically should be encouraged to undergo ophthalmic examination regularly, regardless of any results of Amsler grid self-assessment.

Macular Edema in Central Retinal Vein Occlusion Correlates With Aqueous Fibrinogen Alpha Chain.

Purpose: The global protein profile of the aqueous humor has been found to correlate with the severity of retinal vascular disease. Studying the aqueous humor in central retinal vein occlusion (CRVO) with proteomic techniques may bring insights to the molecular mechanisms underlying the condition. Methods: Aqueous humor samples from treatment naïve patients with CRVO complicated by macular edema (n = 28) and age-matched controls (n = 20) were analyzed by label-free quantification liquid chromatography - tandem mass spectrometry. Best corrected visual acuity (BCVA) was measured as logMAR, and the severity of macular edema was evaluated as central retinal thickness (CRT) with optical coherence tomography. Control samples were obtained prior to cataract surgery. Significantly changed proteins were identified by a permutation-based calculation with a false discovery rate of 0.05. Results: A total of 177 proteins were differentially expressed in CRVO. Regulated proteins were involved in complement activation, innate immune response, blood coagulation, and cell adhesion. Upregulated proteins that correlated with BCVA and CRT included fibrinogen alpha, beta, and gamma chains, fibronectin, Ig lambda-6 chain C region, Ig alpha-1 chain C region, and complement C7. Downregulated proteins that correlated negatively with BCVA, and CRT, included procollagen C-endopeptidase enhancer 1, clusterin, opticin, reelin, fibrillin-1, and cadherin-2. Monocyte differentiation antigen CD14 and lipopolysaccharide-binding protein were increased in CRVO. Conclusions: Fibrinogen chains, fibronectin, and immunoglobulin components correlated with BCVA and CRT, suggesting a multifactorial response. Protective anti-angiogenic proteins, including procollagen C-endopeptidase enhancer 1, clusterin, and opticin, were downregulated in CRVO and correlated negatively with BCVA and CRT.

Efficacy and Safety of Pars Plana Vitrectomy for Primary Symptomatic Floaters: A Systematic Review with Meta-Analyses.

INTRODUCTION: This study aimed to determine the efficacy and safety of pars plana vitrectomy (PPV) as treatment for patients with primary symptomatic vitreous floaters. METHODS: We searched 12 databases for studies performing PPV for primary symptomatic vitreous floaters with at least 3 months follow-up. Two authors reviewed the studies and extracted data. Our main outcome of interest was patient satisfaction/reduction of symptoms/quality of life, but other measures of efficacy and safety were also extracted. Where possible, meta-analyses were performed to provide summary estimates. RESULTS: We identified 18 eligible studies, which included 2077 eyes of 1789 patients. Studies reported that at least 90% of the patients were satisfied or had relief of symptoms. Best corrected visual acuity improved - 0.08 logMAR (95% CI - 0.10 to - 0.06 logMAR, P < 0.0001). Contrast sensitivity improved - 2.26% (95% CI - 3.26 to - 1.26%, P < 0.0001). After surgery, cataract occurred in 31.7% (95% CI 21.7-42.7%), retinal tears/breaks in 2.92% (95% CI 1.38-4.97%), vitreous hemorrhage in 1.97% (95% CI 0.83-3.54%), macular edema in 1.70% (95% CI 0.84-2.83%), retinal detachment in 1.54% (95% CI 0.62-2.82%), glaucoma in 1.04% (95% CI 0.53-1.73%), and endophthalmitis in 0.18% (95% CI 0.02-0.45%). CONCLUSIONS: Postoperative patient satisfaction is high after PPV for primary symptomatic vitreous floaters. However, the patient should be carefully counselled as what to expect from the treatment and understand the risks associated with PPV.

Dexamethasone Intravitreal Implant Is Active at the Molecular Level Eight Weeks after Implantation in Experimental Central Retinal Vein Occlusion.

Central retinal vein occlusion (CRVO) is a visually disabling condition resulting from a thrombus in the major outflow vessel of the eye. The inflammatory response in CRVO is effectively treated with a dexamethasone (DEX) intravitreal implant. Uncovering the proteome changes following DEX implant intervention in CRVO may identify key proteins that mediate the beneficial effects of DEX. In six Göttingen minipigs, CRVO was induced in both eyes with an argon laser using a well-established experimental model. The right eyes were treated with a DEX intravitreal implant (Ozurdex, Allergan), while the left control eyes received a sham injection. Eight weeks after DEX intervention, retinal samples were collected and analyzed with tandem mass tag-based mass spectrometry. DEX implant intervention resulted in the upregulation of peptidyl-prolyl cis-trans isomerase FKBP5 (FKBP5) and ubiquilin-4. Immunohistochemistry showed expression of FKBP5 in the nuclei in all cellular layers of the retina. Cell adhesion molecule 3, tumor necrosis factor receptor superfamily member 16, and trans-1,2-dihydrobenzene-1,2-diol dehydrogenase were downregulated following DEX intervention. The upregulation of the corticosteroid-sensitive protein FKBP5 suggests that the implant remained active at the molecular level after eight weeks of treatment. Future studies may investigate if FKBP5 regulates the efficacy and duration of the DEX implant.

Modern Educational Simulation-Based Tools Among Residents of Ophthalmology: A Narrative Review.

INTRODUCTION: With no specific overview on simulation-based training for educational purposes among residents in ophthalmology, this narrative review attempts to highlight the current literature on modern educational simulation-based tools used to educate residents in ophthalmology. METHODS: We searched databases Web of Science and PubMed between March 15 and July 21, 2022. Relevant and accessible articles and abstracts published after 2006 and in English only were included. RESULTS: Simulation-based cataract surgery is associated with better outcomes in the operating room and faster surgeries. Construct validity has been established across different procedures and levels in simulation-based cataract surgery and simulation-based vitreoretinal surgery. Other simulation-based procedures indicate promising results but in general lack evidence-based validity. DISCUSSION: This narrative review highlights and evaluates the current and relevant literature of modern educational simulation-based tools to train ophthalmology residents in different fundamental skills like simulation-based ophthalmoscopy and complex surgical procedures like simulation-based cataract surgery and vitreoretinal surgery. Some studies attempt to develop simulators for the use in education of ophthalmology residents. Other studies strive to establish validity of the respective procedures or modern education tools and some studies investigate the effect of simulation-based training. The most validated modern educational simulation-based tool is the Eyesi Surgical Simulator (VRmagic, Germany). However, other modern educational simulation-based tools have also been evaluated, including the HelpMeSee Eye Surgery Simulator (HelpMeSee Inc., New York, USA) and the MicroVisTouch Surgical Simulator (ImmersiveTouch, USA). CONCLUSION: Simulation-based training has already been established for residents in ophthalmology to benefit the most from skill-demanding procedures resulting in better learning and better patient handling. Future studies should aim to validate more simulation-based procedures for the teaching of ophthalmology residents so that the evidence is kept at a high standard.

Proteome Analysis of Aflibercept Intervention in Experimental Central Retinal Vein Occlusion.

Aflibercept is a frequently used inhibitor of vascular endothelial growth factor (VEGF) in the treatment of macular edema following central retinal vein occlusion (CRVO). Retinal proteome changes following aflibercept intervention in CRVO remain largely unstudied. Studying proteomic changes of aflibercept intervention may generate a better understanding of mechanisms of action and uncover aspects related to the safety profile. In 10 Danish Landrace pigs, CRVO was induced in both eyes with an argon laser. Right eyes were treated with intravitreal aflibercept while left control eyes received isotonic saline water. Retinal samples were collected 15 days after induced CRVO. Proteomic analysis by tandem mass tag-based mass spectrometry identified a total of 21 proteins that were changed in content following aflibercept intervention. In retinas treated with aflibercept, high levels of aflibercept components were reached, including the VEGF receptor-1 and VEGF receptor-2 domains. Fold changes in the additional proteins ranged between 0.70 and 1.19. Aflibercept intervention resulted in a downregulation of pigment epithelium-derived factor (PEDF) (fold change = 0.84) and endoplasmin (fold change = 0.91). The changes were slight and could thereby not be confirmed with less precise immunohistochemistry and Western blotting. Our data suggest that aflibercept had a narrow mechanism of action in the CRVO model. This may be an important observation in cases when macular edema secondary to CRVO is resistant to aflibercept intervention.

Functional and structural efficacy of a novel combinational therapy of aflibercept and timely focal/grid photocoagulation in diabetic macular oedema: do clinical study results compare favourably with a standard-of-care treated real-world population?

PURPOSE: To evaluate treatment efficacy in diabetic macular oedema (DME) comparing a study population receiving combined intravitreal vascular endothelial growth factor (VEGF) inhibition and focal/grid photocoagulation with a matched, real-world population receiving standard of care treatment. METHODS: In an exploratory study, we included 43 eyes from 32 patients from a previously published study as well as 46 eyes from 38 standard-of-care patients. The study population had received a loading dose of three monthly aflibercept injections followed by focal/grid photocoagulation and additional aflibercept pro re nata. Principal measurements at 12 months were numbers of intravitreal injections, best corrected visual acuity (BCVA) and central retinal thickness (CRT). RESULTS: At baseline, there were no differences between groups regarding age, sex, body mass index, haemoglobin A1 C, systolic pressure or type of diabetes, but the study population had a higher diastolic pressure (81.6 versus 72.1 mmHg, p = 0.03) and a lower duration of diabetes (12.3 versus 23.2 years, p = 0.03). At month 12, patients in the study group had a higher visual acuity (79.6 versus 74.3 ETDRS letters, p = 0.03), despite having received fewer aflibercept injections (4.4 versus 5.9, p < 0.01) with a higher likelihood of having only received the three mandatory injections in the loading phase (39.5% versus 13.0%, p = 0.01). CONCLUSION: In comparison to a matched, real-world DME-population, patients in combined treatment with intravitreal aflibercept and postloading focal/grid photocoagulation obtained a better functional outcome despite having received fewer intravitreal injections. Future randomized studies are needed to evaluate the long-term efficacy of this combined treatment regimen.

Navigated laser and aflibercept versus aflibercept monotherapy in treatment-naïve branch retinal vein occlusion: A 12-month randomized trial.

PURPOSE: Angiostatic agents have proven effective in the treatment of macular oedema in patients with branch retinal vein occlusion (BRVO). However, treatment is inconvenient and expensive, and novel treatment regimens are warranted. We aimed to evaluate if combination treatment of navigated central retinal laser and aflibercept lowered the treatment burden in these patients. METHODS: Treatment-naïve patients with BRVO and macular oedema were included at two centres and randomized 1:1 to three monthly injections of 2.0 mg aflibercept with (Group A) or without (Group B) navigated central laser, followed by aflibercept as needed from month 4 through 12. Re-treatment need was evaluated, and secondary endpoints included functional and anatomical outcomes and safety evaluated by retinal microperimetry. RESULTS: We evaluated 41 eyes of 41 patients with a mean age of 69.6 years. Baseline median best-corrected visual acuity (BCVA) was 70.0 letters, and median central retinal thickness (CRT) was 502 µm with no difference between Groups A (n = 21) and B (n = 20). Percentage of patients needing re-treatment after month three was 71% and 80% (p = 0.72). At month 12, groups did not differ in number of injections after loading (1 versus 2, p = 0.43), change in BCVA (+12.8 versus +15.1 letters, p = 0.48), CRT (-195 versus -181 µm, p = 0.82), or retinal sensitivity (+3.3 versus +4.1 dB, p = 0.67). CONCLUSION: In treatment-naïve BRVO patients, addition of navigated central laser to aflibercept did not lower treatment burden or affect functional or anatomical outcomes. A low number of intravitreal injections were needed for successful outcome in both treatment arms.

Diabetic retinopathy screening in the emerging era of artificial intelligence.

Diabetic retinopathy is a frequent complication in diabetes and a leading cause of visual impairment. Regular eye screening is imperative to detect sight-threatening stages of diabetic retinopathy such as proliferative diabetic retinopathy and diabetic macular oedema in order to treat these before irreversible visual loss occurs. Screening is cost-effective and has been implemented in various countries in Europe and elsewhere. Along with optimised diabetes care, this has substantially reduced the risk of visual loss. Nevertheless, the growing number of patients with diabetes poses an increasing burden on healthcare systems and automated solutions are needed to alleviate the task of screening and improve diagnostic accuracy. Deep learning by convolutional neural networks is an optimised branch of artificial intelligence that is particularly well suited to automated image analysis. Pivotal studies have demonstrated high sensitivity and specificity for classifying advanced stages of diabetic retinopathy and identifying diabetic macular oedema in optical coherence tomography scans. Based on this, different algorithms have obtained regulatory approval for clinical use and have recently been implemented to some extent in a few countries. Handheld mobile devices are another promising option for self-monitoring, but so far they have not demonstrated comparable image quality to that of fundus photography using non-portable retinal cameras, which is the gold standard for diabetic retinopathy screening. Such technology has the potential to be integrated in telemedicine-based screening programmes, enabling self-captured retinal images to be transferred virtually to reading centres for analysis and planning of further steps. While emerging technologies have shown a lot of promise, clinical implementation has been sparse. Legal obstacles and difficulties in software integration may partly explain this, but it may also indicate that existing algorithms may not necessarily integrate well with national screening initiatives, which often differ substantially between countries.

Proteomic analysis of vitreous humour of eyes with diabetic macular oedema: a systematic review.

The pathophysiology of diabetic macular oedema (DME) remains poorly understood. Proteomic analysis of the vitreous using mass spectrometry (MS) can potentially identify proteins of pathophysiological importance. In this systematic review, we summarize the available evidence on protein changes in DME detected by MS. We systematically searched 13 literature databases on 19 September 2021. Eligible studies were defined as those using samples from human eyes with DME analysed with MS. Two authors assessed the studies for eligibility, extracted data and evaluated risk of bias independently. Six eligible studies were identified. All were designed in a cross-sectional fashion comparing results to either a non-diabetic control group or a control group without DME. A total of 62 eyes from 60 patients contributed as study group and 48 eyes from 48 patients served as control group. Proteomic analyses revealed significant differences in the vitreous protein levels in patients with DME when compared with controls. Three studies or more identified increased contents of apolipoprotein A-I, apolipoprotein A-II, apolipoprotein A-IV, apolipoprotein C-III, gelsolin, pigment epithelium-derived factor, serum albumin, transthyretin, vitamin D-binding protein in DME. Two studies found increased levels of complement factors B and C3. Protein changes reproduced across the studies suggested that DME was associated with retinal lipid accumulation, angiogenesis, retinal protective mechanisms, inflammation and complement activation. Proteome studies support the multifactorial pathogenesis of DME as proteins with highly different biological functions are regulated in DME. An important number of proteins differ, provide pathophysiological insight and suggest the direction for future research.