The I-OPTA Questionnaire: A National Assessment of Patients with Neovascular Age-Related Macular Degeneration.

INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is the leading cause of irreversible vision loss in developed countries. However, a significant gap persists in understanding this population, exacerbated by their advanced age and visual impairments, which can hinder research participation and access to healthcare. The purpose of this study was to describe the content of the questionnaire and the participating patients with nAMD. METHODS: The survey includes patients diagnosed with nAMD who had previously received treatment or were currently undergoing intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. Participants were recruited using various methods, as reaching out to patients who are no longer receiving treatment poses a particular challenge. A patient and public advisory board assisted throughout the study period. RESULTS: Of the 713 electronic invitations sent out, 494 (69.3%) patients responded to the questionnaire, with an additional 57 responses obtained through e-mail or telephone interviews. Due to the exclusion of 16 responses, there were a total of 535 valid responses, including 176 from patients previously treated and 359 from those currently undergoing treatment for nAMD. The median age of respondents was 79.9 years (interquartile range [IQR] 75.5-84.7), with 59.8% being women. Among them, 53.2% were married, while 43.1% lived alone. CONCLUSIONS: Data from the I-OPTA (Identification of Patient-Reported Barriers in Treatment for nAMD) questionnaire allows future exploration of patients who are no longer receiving treatment, patients' knowledge about preventive measures, and the impact of nAMD on visual function and quality of life. Future research, including studies that integrate data from corresponding retinal images and Danish national registers, has the potential to generate invaluable knowledge, providing benefits to both patients and healthcare professionals.

The Impact of the COVID-19 Pandemic on Tele-ophthalmology-Based Retinal Screening.

INTRODUCTION: This study reports our experiences with systematic retinal screening in Denmark through optometrists with access to tele-ophthalmological services before, during, and after the COVID-19 pandemic. METHODS: We evaluated an optometrist-based retinal screening system with a referral option for tele-ophthalmological service by a consultant ophthalmologist within the time period of August 1, 2018 to September 30, 2023. The optometrist collected patient history, refraction, best-corrected visual acuity, intraocular pressure, basic slit-lamp examination, 4-in-1 visual field report, and retinal imaging using color fundus 45° photography. Tele-ophthalmological services were provided by consultant ophthalmologists. Within pre-defined periods of pre-COVID-19, COVID-19, and post-COVID-19, we evaluated the rate of referrals to the tele-ophthalmological service, diagnoses made, and referrals to the public healthcare system. RESULTS: A total of 1,142,028 unique individuals, which corresponded to 19.1% of the entire population of Denmark, underwent screening by the optometrists; 50,612 (4.4%) of these individuals were referred to the tele-ophthalmological examination by consultant ophthalmologists. A referral for further ophthalmic examination, either at hospital or at an ophthalmic practice, was made for 10,300 individuals (20.4% of those referred for tele-ophthalmology, corresponding to 0.9% of the population screened). The referral rate from the screening to the tele-ophthalmological service increased from before COVID-19 (3.4%) to during COVID-19 (4.3%) and further after COVID-19 (6.4%). This increase coincided with an increasing prevalence of conditions seen in the tele-ophthalmological service. CONCLUSION: During a period of 5 years, 19.1% of the entire population of Denmark underwent retinal screening. This provided an adjunctive health service during a period of severe strain on the public healthcare system, while limiting the number of excessive referrals to the public healthcare system. Temporal trends illustrated an increased pattern of use of a large-scale tele-ophthalmological system.

Real-world efficacy of intravitreal faricimab for neovascular age-related macular degeneration: a systematic review.

BACKGROUND: To systematically review the real-world outcomes of intravitreal faricimab treatment in patients with neovascular age-related macular degeneration (nAMD) to evaluate its efficacy and safety in clinical settings. This study was conducted due to the need for real-world evidence to complement the findings from controlled clinical phase-III trials. METHODS: A systematic literature search was conducted on March 17, 2024, across 11 databases, utilizing search terms specifically tailored each database. All studies were reviewed qualitatively with specific focus on the outcomes of interest: the best-corrected visual acuity (BCVA), the central retina thickness (CRT), and the burden of therapy. RESULTS: We identified a total of 22 eligible studies of 1762 eyes from 1618 patients with nAMD. Studies reported that intravitreal faricimab injections maintained BCVA in patients with previously treated eyes and demonstrated statistically significant improvement in patients with treatment-naïve eyes. The CRT was reduced after intravitreal faricimab therapy. Faricimab was well-tolerated, with no significant safety concerns identified, and reduced the overall burden of therapy. CONCLUSION: Real-world studies corroborate the conclusions drawn from phase-III trials regarding faricimab treatment, demonstrating improvement in both visual and anatomical outcomes. Additionally, no significant safety issues were identified, as the treatment was generally well-tolerated and reduced the overall burden of therapy in the real-world settings.

Diagnostic accuracy of OCT angiography for macular neovascularization in central serous chorioretinopathy: A systematic review and meta-analysis.

Identifying macular neovascularization (MNV) in eyes with central serous chorioretinopathy (CSC) has important implications for its management. Optical coherence tomography angiography (OCTA) is increasingly used for this purpose. Here, we systematically reviewed the literature and conducted meta-analysis to determine the diagnostic accuracy of OCTA for detecting MNV in eyes with CSC. We systematically searched the literature in 12 databases for relevant studies from database inception until 18 November 2023. Eligible studies had eyes with CSC with MNV and CSC without MNV. Index test was OCTA. Reference test was retinal dye angiography. Study selection and data extraction were performed in duplicate, and study was evaluated using the Quality Assessment of Diagnostic Accuracy Studies 2. Our main outcome of interest was the sensitivity and specificity of OCTA for detecting MNV in CSC. Pooled diagnostic test accuracy estimates were computed using MetaDTA. Of 177 records screened, seven fulfilled the eligibility criteria for our study. These studies summarized data from a total of 1061 eyes. Summary estimate sensitivity and specificity to diagnose MNV in eyes with CSC using OCTA was 92.9% (95% CI: 81.7%-97.5%) and 99.4% (95% CI: 84.1%-100.0%), respectively. The main source of bias across studies was the reference standard, as four studies used multimodal imaging including OCTA for the reference standard. OCTA alone is excellent for detecting MNV in CSC compared to retinal dye angiography or multimodal imaging. Using OCTA first before considering retinal dye angiography could potentially save an important number of retinal dye angiographies.

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.

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.

Presence and development of diabetic retinopathy in 16 999 patients with type 1 diabetes in the Danish Registry of Diabetic Retinopathy.

PURPOSE: To evaluate the five-year incidence of diabetic retinopathy (DR) and associated risk markers in patients with type 1 diabetes in the national Danish DR-screening programme. METHODS: Based on national data, we included all 16 999 patients with type 1 diabetes in the Danish Registry of Diabetic Retinopathy, who attended the national screening programme in the period 2013-2018. According to the worse eye at first screening, DR was classified (levels 0-4) and linked with various national health registries to retrieve information on diabetes duration, systemic comorbidity, and medication. RESULTS: At first screening, median age and duration of diabetes were 45.0 and 16.7 years, and 57.5% were males. The prevalence and five-year incidences for DR and progression to proliferative DR (PDR) were 44.2%, 8.9% and 2.0%, respectively. In multivariable Cox models, the incidence endpoints were associated with duration of diabetes (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.63-1.89, and HR 2.04, 95% CI 1.73-2.40 per 10 years), moderately low Charlson Comorbidity Index score (HR 1.27, 95% CI 1.10-1.47, and HR 2.80, 95% CI 2.23-3.51), and use of blood pressure lowering medication (HR 1.20, 95% CI 1.05-1.36, and HR 1.98, 95% CI 1.53-2.57). CONCLUSION: In a study of all patients with type 1 diabetes from the Danish DR-screening programme, we identified duration of diabetes, systemic disease and use of anti-hypertensive treatment as consistent risk markers for incident and progressive DR.

Perspectives and Update on the Global Shortage of Verteporfin (Visudyne®).

An ongoing global shortage of verteporfin (Visudyne®) limits the treatment possibilities for several chorioretinal diseases, including central serous chorioretinopathy, choroidal hemangioma, and polypoidal choroidal vasculopathy. Verteporfin is required to perform photodynamic therapy in these ocular diseases. Therefore, the current situation has a substantial impact on eye care worldwide. The worldwide supply of verteporfin appears to be manufactured by a single factory, which is situated in the United States. The distribution of verteporfin is done by different companies for different regions of the world. Official communication on the shortage by the responsible companies has been scarce and over the past years several promises with regards to resolution of the shortage have not been fulfilled. The delivery of new batches of verteporfin is at irregular intervals, unpredictable, and may not be fairly balanced between different regions or countries in the world. To ensure a fair distribution of available verteporfin within a country, several measures can be taken. In the Netherlands, a national committee, consisting of ophthalmologists, is in place to arrange this. On the European level, the European Union and European Medicine Agency have plans to monitor medicine shortages more closely and to intervene if necessary. With a more intensified monitoring and regulation of medicine supplies, future impending shortages may be prevented. Remarkably, the amount of medicine shortages is increasing, having a significant and sometimes irreversible impact on patient care. Thus, efforts should be undertaken to minimize the consequences and, whenever possible, to prevent future medicine shortages.

VEGF Inhibition Associates With Decreased Risk of Mortality in Patients With Neovascular Age-related Macular Degeneration.

Purpose: Controversy exists regarding the systemic safety of intravitreal VEGF inhibitors in the treatment of neovascular age-related macular degeneration (nAMD). We aimed to investigate the potential impact of VEGF inhibitor treatment on the risk of all-cause mortality and cardiovascular disease (CVD) among patients with nAMD. Design: A nationwide register-based cohort study with 16 years follow-up. Participants: Patients with nAMD exposed with VEGF inhibitors (n = 37 733) and unexposed individuals without nAMD (n = 1 897 073) aged ≥ 65 years residing in Denmark between January 1, 2007, and December 31, 2022. Methods: Cox proportional hazards analysis was conducted to assess the effect of intravitreal VEGF inhibitor treatment on all-cause mortality and incident CVD. Main Outcome Measures: In a predefined analysis plan we defined primary outcomes as hazard ratios (HRs) of all-cause mortality and a composite CVD endpoint in patients with nAMD treated with VEGF inhibitors compared with individuals without nAMD. The secondary outcomes encompassed analyses that explored the impact of the number of doses and the association between exposure and outcome over a specific time period. Results: Overall, 63.7% of patients with nAMD were women with an average age of 69.9 years (interquartile range 65.0-76.0 years). Patients exposed to VEGF inhibitors demonstrated a reduced risk of all-cause mortality compared with individuals without nAMD (HR, 0.79; 95% confidence interval [CI], 0.78-0.81), and an increased risk of composite CVD (HR, 1.04; 95% CI, 1.01-1.07). The decreased risk of all-cause mortality persisted, but there was no significant association between VEGF inhibitor treatment and CVD when patients with nAMD were grouped by the number of doses or considered exposed within 60 days postinjection. Conclusions: Our study revealed a decreased risk of all-cause mortality and a 4% increased risk of CVD among patients with nAMD exposed with VEGF inhibitors. The decreased risk of mortality is unlikely to be directly pathophysiologically related to VEGF inhibitor treatment. Instead, we speculate that patients undergoing VEGF inhibitor treatment are, on average, individuals in good health with adequate personal resources. Therefore, they also have a higher likelihood of overall survival. These findings strongly support the safety of VEGF inhibitor treatment in terms of all-cause mortality and CVD among patients with nAMD. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Blinded by Stress: A Patient and Physician Perspective on Central Serous Chorioretinopathy.

This commentary is co-authored by a patient with central serous chorioretinopathy (CSC), which is the fourth most common exudative maculopathy. The patient, a young and profiled member of the Danish Parliament, kindly shares his experience living with stress, onset of symptoms, and the experience of being diagnosed with CSC and receiving photodynamic treatment. The experiences of the patient are put into perspective by an ophthalmologist.

In this patient­physician perspective, a patient with central serous chorioretinopathy shares his experience. Central serous chorioretinopathy mainly affects men aged 30­50, is associated with stress, and the main symptom is blurring of central vision. The patient describes his life and work as member of the Danish Parliament, living with stress, being diagnosed with central serous chorioretinopathy, receiving treatment, and finally adapting to a new life in which work­life balance is prioritized to avoid excessive stress.

Central serous chorioretinopathy: An evidence-based treatment guideline.

Central serous chorioretinopathy (CSC) is a relatively common disease that causes vision loss due to macular subretinal fluid leakage and it is often associated with reduced vision-related quality of life. In CSC, the leakage of subretinal fluid through defects in the retinal pigment epithelial layer's outer blood-retina barrier appears to occur secondary to choroidal abnormalities and dysfunction. The treatment of CSC is currently the subject of controversy, although recent data obtained from several large randomized controlled trials provide a wealth of new information that can be used to establish a treatment algorithm. Here, we provide a comprehensive overview of our current understanding regarding the pathogenesis of CSC, current therapeutic strategies, and an evidence-based treatment guideline for CSC. In acute CSC, treatment can often be deferred for up to 3-4 months after diagnosis; however, early treatment with either half-dose or half-fluence photodynamic therapy (PDT) with the photosensitive dye verteporfin may be beneficial in selected cases. In chronic CSC, half-dose or half-fluence PDT, which targets the abnormal choroid, should be considered the preferred treatment. If PDT is unavailable, chronic CSC with focal, non-central leakage on angiography may be treated using conventional laser photocoagulation. CSC with concurrent macular neovascularization should be treated with half-dose/half-fluence PDT and/or intravitreal injections of an anti-vascular endothelial growth factor compound. Given the current shortage of verteporfin and the paucity of evidence supporting the efficacy of other treatment options, future studies-ideally, well-designed randomized controlled trials-are needed in order to evaluate new treatment options for CSC.

Short-term outcomes of treatment switch to faricimab in patients with aflibercept-resistant neovascular age-related macular degeneration.

PURPOSE: To report short-term outcomes of treatment switch to faricimab in real-world patients with aflibercept-resistant neovascular age-related macular degeneration (AMD). METHODS: Single-center, retrospective cohort study with chart-review using electronic injection database, electronic medical records, and optical coherence tomography (OCT) data from May to September 2023. RESULTS: A total of 50 eyes of 46 patients were analyzed. Faricimab treatment led to absence of fluid in 32% of the eyes and a reduction of fluid in 84% of the eyes. There was a statistically significant decrease in central retinal thickness (CRT) and pigment epithelial detachment (PED) height in those that responded to the switch (median difference: - 31 µm, IQR: 55, p < 0.0001 and median difference: - 21 µm, IQR: 36, p < 0.0001, respectively) and a statistically significant increase in CRT (median difference: + 19 µm, IQR: 20, p = 0.0143) and no change in PED height (median difference: + 22 µm, IQR: 64, p = 0.1508) in those that did not. Best-corrected visual acuity (BCVA) showed marginal decrease with low statistical significance. No ocular or systemic safety events were observed. CONCLUSIONS: Our findings suggest that switching to faricimab is generally safe and effective in patients with neovascular AMD who are otherwise difficult to treat and have residual fluid despite frequent injections with aflibercept. We observed a high rate of morphological response to the treatment switch, improvement of anatomical parameters with about one-third of patients having dry macula following a single injection, and a marginal change in BCVA. Sustainability of these results requires further investigation. STUDY REGISTRATION: ClinicalTrials.gov registration number: NCT06124677. Date of registration: 09/11/2023, retrospectively registered.

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.

Systemic adverse events and all-cause mortality following same-session bilateral intravitreal anti-VEGF injections: a systematic review.

PURPOSE: To review the risk of systemic adverse events and all-cause mortality following same-day bilateral anti-VEGF injections. METHODS: Twelve literature databases were searched for studies on same-session bilateral intravitreal anti-VEGF injections. Studies reporting on systemic adverse events and mortality were included. Data extraction was made independently by two authors and discussed afterwards until consensus was reached. RESULTS: Seven studies were included with a total of 13,406 intravitreal anti-VEGF injections (6703 bilateral injections sessions) given to 689 patients. Across all studies, mean age of patients ranged from 55.7 to 82.5 years, and mean follow-up times ranged from 1.3 to 41 months. Six studies reported on systemic adverse events: Two cases of non-fatal cardiac adverse events were reported after 12,964 injections (6482 bilateral injection sessions) in 626 patients. Four studies reported on death: 12 deaths were recorded after 6233 bilateral injection sessions in a total population of 554 subjects. CONCLUSIONS: We suggest that the risk of non-fatal systemic adverse events and death after same-session bilateral anti-VEGF injection is reasonably low, but larger studies with follow-ups of several years are needed to quantify the exact risk. STUDY REGISTRATION: Prospectively registered in PROSPERO, registration ID: CRD42023428254, registration date: 20/05/2023.

Effect of Needle Gauge Size on Pain During Intravitreal Anti-VEGF Injection: A Systematic Review and Network Meta-Analysis.

INTRODUCTION: Concerns related to pain from intravitreal injections are one of the key factors mentioned by patients when asked about therapy. In this systematic review and network meta-analysis, we evaluate the literature of comparative clinical trials on the relationship between needle gauge size and pain experience during intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. METHODS: We searched 12 literature databases on 14 October 2023 for comparative studies of gauge sizes for intravitreal anti-VEGF injections. The primary outcome of interest was the reported pain experience immediately after the injection. All outcomes of pain were transformed into standardized effect sizes using Cohen's d. Using a network meta-analysis approach, we were able to compare all gauge sizes and rank them according to the reported pain experience. RESULTS: We identified nine eligible studies with data on a total of 998 patients and 1004 eyes. Needle sizes studied were 26-gauge, 27-gauge, 29-gauge, 30-gauge, 32-gauge, 33-gauge, and 34-gauge. A complete network was present, which allowed for a network meta-analysis. We used the thickest (26-gauge) needle as the reference group and observed a clear trend of lower pain experience with thinner gauge sizes (d: -0.4, d: -2.7, d: -3.8, d: -4.8, d: -4.5, and d: -5.3; respectively, for 27-gauge, 29-gauge, 30-gauge, 32-gauge, 33-gauge, and 34-gauge). CONCLUSION: A gauge size of 30 or thinner may minimize patient discomfort related to intravitreal anti-VEGF therapy.

Topical non-steroidal anti-inflammatory drugs for central serous chorioretinopathy: A systematic review and meta-analysis.

Central serous chorioretinopathy (CSC) is a prevalent exudative maculopathy and the ongoing verteporfin shortage restricts current treatment possibilities. Topical non-steroidal anti-inflammatory drugs (NSAID) have previously been proposed as a treatment for CSC, although its exact efficacy remains unclear. In this systematic review and meta-analysis, we outlined the efficacy of topical NSAIDs for the treatment of CSC. We searched 11 literature databases on 13 December 2022, for any study describing topical NSAID treatment for CSC. Thirteen eligible studies were included with a total of 1001 eyes of 994 patients with CSC. Six studies were case reports, two were cohort studies and five were non-randomized comparative studies. Where specified, topical NSAIDs used were bromfenac 0.09%, diclofenac 0.1%, ketorolac 0.4% and 0.5%, pranoprofen 0.1%, and nepafenac 0.1% and 0.3%. Studies were predominantly of cases with acute CSC and several case studies reported treatment outcomes simultaneously with discontinuation of corticosteroid use, which complicated treatment evaluation. Meta-analyses of comparative studies revealed a statistically significant but clinically irrelevant best-corrected visual acuity improvement of -0.04 logMAR (95% CI: -0.07 to -0.01 logMAR; p = 0.01) at 1-month follow-up, which became statistically insignificant at 3-month follow-up (-0.03 logMAR; 95% CI: -0.06 to 0.003 logMAR; p = 0.08). Further, we found no benefit in complete subretinal fluid resolution at 1-month follow-up (OR: 1.20; 95% CI: 0.81-1.76; p = 0.37) or 3-month follow-up (OR: 1.17; 95% CI: 0.86 to 1.59; p = 0.33). Taken together, available evidence does not support the use of topical NSAIDs for the treatment of CSC.

Clinical Trials and Future Outlooks of the Port Delivery System with Ranibizumab: A Narrative Review.

The port delivery system (PDS) of anti-VEGF therapy provides continuous delivery of ranibizumab (RBZ). In October of 2021, the American Food and Drug Administration (FDA) approved the PDS with RBZ as a treatment option for neovascular age-related macular degeneration (nAMD). As the field of PDS with RBZ is progressing rapidly, this narrative review provides a much-needed overview of existing clinical trials as well as ongoing and upcoming trials investigating PDS with RBZ. The phase 2 LADDER trial reported that the mean time to first refill with RBZ PDS 100 mg/ml was 15.8 months (80% CI 12.1-20.6), and pharmacokinetic profiling revealed a sustained concentration of RBZ in serum and aqueous humor. Later, the phase 3 ARCHWAY trial reported that PDS with RBZ (100 mg/ml) refilled every 24 weeks was non-inferior to monthly intravitreal injection (IVI) with RBZ (0.5 mg) in patients with nAMD over 9 months and 2 years. However, patients with PDS had a higher rate of adverse events including vitreous hemorrhage and endophthalmitis. Patients indicate high treatment satisfaction with both PDS and IVI, but the lower number of treatments with PDS was reported as a preferred choice. Several ongoing and future clinical trials, of which details are discussed in this paper, are further exploring the potentials of PDS with RBZ. We conclude that the PDS provides continuous deliverance of RBZ and that clinical efficacy levels are non-inferior to IVI therapy for nAMD. Yet, a higher rate of adverse events remains a concerning detail for widespread implementation. Future studies are warranted to better understand which patients may benefit best from this treatment approach, if long-term efficacy can be sustained, and if safety of PDS can be further improved.

Prevalence of optic disc drusen: A systematic review, meta-analysis and forecasting study.

Optic disc drusen (ODD) are calcium-containing deposits in the optic nerve head, capable of causing visual field defects and sudden visual loss. The underlying pathophysiology remains inadequately understood and treatment options are missing. In this paper, we systematically reviewed prevalence studies of ODD in non-selected populations to provide an overview of its prevalence, conducted meta-analyses to determine modality-specific prevalence estimates and performed a forecasting study to estimate current and future global population number of individuals with ODD. We searched 11 literature databases on 25 October 2022 for prevalence studies of ODD in non-selected populations. Eight eligible studies provided data from a total of 27 463 individuals. Prevalence estimates were stratified according to diagnostic modalities: ophthalmoscopy 0.37% (95% CI: 0.10-0.95%), fundus photography 0.12% (95% CI: 0.03-0.24%), spectral domain optical coherence tomography with enhanced depth imaging 2.21% (95% CI: 1.25-3.42%) and histopathology 1.82% (95% CI: 1.32-2.38%). Using histopathology-based summary prevalence estimate, we forecast 145 million individuals with ODD currently, a number expected to increase further due to world population growth. These numbers underscore the importance of including ODD in health education and highlight the necessity of continuing research in ODD.

Association between visual impairment and suicide: A systematic review and meta-analysis.

Visual impairment severely impacts the life of the patients. In this study, we systematically reviewed studies on the potential relationship between visual impairment and suicidal behaviour, and conducted meta-analyses on the risk estimates. We searched 11 literature databases on 20 October 2022 and identified a total of 10 eligible studies with 5.8 million participants. Suicide behaviour was investigated according to three domains: suicide ideation, suicide attempt and suicide death. In the 10 eligible studies, seven reported data on suicide ideation, five reported data on suicide attempt, and three reported data on suicide death. All summary estimates extracted for use in the meta-analyses were adjusted estimates of association since we acknowledged that depression as well as other confounding factors may play an important role. We found that visual impairment was a significant risk factor of suicide ideation (OR 1.83; 95% CI: 1.40-2.40; p = 0.000012), suicide attempt (OR 2.62; 95% CI: 1.29-5.31; p = 0.0077) and suicide death (OR 7.00; 95% CI: 2.30-21.4; p = 0.000063). These high increases in risk of suicide from visual impairment underscore the importance of eye health on the overall mental health, and the potential devastating consequences of insufficient access to eye care, lack of treatment possibilities for any reason or low political priority of eye care.