The impact of COVID-19 on aflibercept treatment of neovascular AMD in Sweden - data from the Swedish Macula Register.

BACKGROUND: The purpose of the study was to compare the real-world aflibercept treatment and visual outcomes, and to examine the adherence to pandemic guidelines in two groups of patients with treatment-naïve neovascular age-related macular degeneration (nAMD) before and during the first year of the COVID-19 pandemic in Sweden up to the 1-year follow-up. METHODS: This is a retrospective observational study including 2915 treatment naïve eyes with nAMD. Using data from the Swedish Macula Register (SMR), 1597 eyes initiating treatment between 1 July 2018 and 31 January 2019 (pre-pandemic group) were compared with 1318 eyes starting treatment between 1 February and 31 August 2020 (pandemic group). The eyes were then followed for 1 year ± 2 months, hence the first group was unaffected by the pandemic while the second group was affected. The focus was on baseline characteristics, visual acuity (VA) change from baseline, number of injections, treatment regimen, number of appointments and the frequency and length of appointment delays. The Wilcoxon Signed-Rank Test was used to compare baseline VA to follow-up VA within the respective groups. The Mann-Whitney U-test and Fisher's exact test were used to compare outcomes between the groups. RESULTS: Baseline characteristics were similar between the two groups. The percentage of eyes with an available follow-up VA after 1 year was 58% in the pre-pandemic group vs. 44% in the pandemic group. VA in the pre-pandemic group had increased significantly after 1 year, from 62.2 ± 14.1 letters to 64.8 ± 16.1 letters (n = 921); p < 0.0001. In the pandemic group, VA increased from 61.1 ± 15.8 to 64.9 ± 16.9 (n = 575); p < 0.0001. There was no significant difference in mean VA change between the groups; p = 0.1734. The pre-pandemic group had significantly more delays than the pandemic group, 45% vs. 36%; p < 0.0001. CONCLUSIONS: The pre-pandemic and pandemic groups had similar VA gains at 1-year follow-up, but with a reduced number of available VA in the pandemic group. Clinics were able to implement and prioritize injection visits excluding VA measurements, helping to reduce delays and maintain VA gains during the COVID-19 pandemic.

Occurrence of uveitis in a population-based cohort of inflammatory bowel diseases followed for 10 years: an observational study.

OBJECTIVE: The coexistence of inflammatory bowel diseases (IBDs) and uveitis has been known for 100 years. The reported frequency by which these conditions appear in the same patient has varied considerably. The aim of this study was to investigate the occurrence of uveitis in a well-defined population-based cohort of patients with IBD including all age groups and followed for at least 10 years. METHOD AND ANALYSIS: All newly diagnosed patients with ulcerative colitis and Crohn's disease in the county of Uppsala between 2005 and 2009 were prospectively followed. At the end of 2022, the medical notes were checked and all contacts with the healthcare system regarding ocular symptoms were scrutinised. RESULTS: A total of 330 patients with ulcerative colitis and 153 patients with Crohn's disease were included in the cohort. Four hundred and forty-two of these (91.5%) could be followed for 10 years or until death. Thirteen patients with ulcerative colitis were affected by uveitis (3.9%), and one of the patients with Crohn's disease (0.7%). Most often the uveitis was diagnosed after the bowel disease (median 8.9 years, 7.7 years SD). CONCLUSION: Low occurrence of uveitis was identified in the IBD population. All affected individuals except one were diagnosed with ulcerative colitis. Most of the patients had their eye disease around 10 years later than their IBD diagnosis. It is suggested that systemic anti-inflammatory treatment for the IBD protects against intraocular inflammation in this cohort.

Cataract surgery in neovascular AMD: impact on visual acuity and disease activity.

BACKGROUND: Cataract and neovascular age-related macular degeneration (nAMD) often co-exist and both contribute to impaired vision. It has been debated whether cataract surgery can increase nAMD activity. The purpose of this retrospective study was to investigate the impact of cataract surgery on visual acuity, treatment intensity for nAMD and macular morphology in patients with on-going treatment for nAMD. METHODS: Data was obtained from the Swedish Macular Register, the Swedish National Cataract Register, optical coherence tomography (OCT) images and patient charts. All eyes were treated at the Department of Ophthalmology at the County Hospital of Västmanland, Västerås, Sweden. Follow-up was 6 months after surgery. The study was approved by the Swedish Ethical Review Authority. RESULTS: In total, 156 patients (168 eyes) were included. The mean age at cataract surgery was 82 (standard deviation, SD 6) years. Both distance and near visual acuity improved after surgery. Distance visual acuity increased from 59 (SD 12) to 66 (SD 15) letters ETDRS (P < 0.001). Proportion of eyes with normal near visual acuity increased from 12 to 41%. The anti-vascular endothelial growth factor (VEGF) treatment intensity remained unchanged: mean of 3.4 (SD 1.9) and 3.3 (SD 1.7) treatments were given 6 months pre- and postoperatively, respectively. The prevalence of intraretinal fluid (IRF) in the macula increased from 22 to 31% postoperatively, while subretinal fluid, fluid under the pigment epithelium (sub-RPE fluid) and central retinal thickness were unaltered. In eyes with new IRF, improvement in visual acuity and number of anti-VEGF treatments were similar to eyes without new IRF. CONCLUSION: Cataract surgery improved visual acuity in patients with on-going treatment for nAMD and did not affect anti-VEGF treatment intensity. Macular morphology remained unchanged. The slight increase in intraretinal fluid after surgery was not found to affect visual acuity or anti-VEGF treatment intensity. It is hypothesized that this might indicate that it represents degenerative intraretinal cystic fluid.

Health care registers can be instrumental for endpoint capture in clinical diabetes trials: example of microvascular complications in Swedish patients with type 2 diabetes.

AIMS: SMARTEST is a register-based randomized clinical trial (RRCT) that compares dapagliflozin to metformin in early-stage type 2 diabetes. The primary outcome includes progression of microvascular complications based on data from the Swedish National Diabetes Register (NDR). In this sub-study, the aim was to validate microvascular complication variables in the NDR against electronic health records (EHRs). METHODS: Data were extracted from EHRs of 276 SMARTEST participants with a median observation period of 3 years in the Uppsala, Örebro and Sörmland counties and compared with NDR data. Agreement was determined for all corresponding data entries as well as for progression of microvascular complications after randomization. RESULTS: The agreement for all corresponding data entries was 98.9% (Intraclass Correlation Coefficient 0.999) for creatinine and eGFR, 95.1% for albuminuria, 91.6% for foot-at-risk and 98.2% for retinopathy status (Kappa 0.67-0.91). The agreement for progression of microvascular complications was 98.0% for CKD stage, 98.9% for albuminuria grade, 96.3% for foot-at-risk grade and 99.6% for retinopathy grade progression (Gwet's AC1 0.96-1.00). CONCLUSION: Microvascular complication variables in the NDR show good agreement with EHR data. The use of a well-established national health care registry, exemplified by the NDR, for endpoint collection in RRCTs such as SMARTEST is supported by this study.

No findings of SARS-CoV-2 in conjunctival swabs from patients at an emergency outpatient ophthalmological healthcare facility in a Swedish county hospital: a cross-sectional study.

BACKGROUND: COVID-19 is caused by SARS-CoV-2. Virus has been found in conjunctiva of hospitalised patients with COVID-19. Conjunctivitis has also been reported as a presenting symptom of disease. OBJECTIVE: The aims of the study were to investigate the prevalence of SARS-CoV-2 in the conjunctiva and throat among patients presenting at the emergency outpatient ophthalmological healthcare facility at a county hospital along with investigating the seroprevalence of SARS-CoV-2 among staff at the department. METHODS AND ANALYSIS: Swabs from conjunctiva and throat of patients were analysed with real-time reverse transcriptase PCR (RT-PCR) for SARS-CoV-2. Blood samples for serological analysis were obtained from staff. A questionnaire was used to investigate symptoms associated with COVID-19 during the last 3 months as well as symptoms for which the patients were seeking ophthalmological healthcare. RESULTS: In total, 68 patients and 70 individuals from the staff were included in the study. Conjunctivitis was observed in 7% of patients. One patient, presenting with reduced visual acuity due to preretinal haemorrhage in the macula, was positive for SARS-CoV-2 in throat swab. Contact tracing was negative. All other RT-PCR tests were negative. Seropositivity for SARS-CoV-2 was found in 4% of staff. CONCLUSIONS: Our study demonstrated low prevalence of SARS-CoV-2 among patients as well as low seroprevalence of SARS-CoV-2 IgG-antibodies among staff at the ophthalmological ward. The risk for contracting COVID-19 at the department was small. Follow-up investigation is planned.

Switching anti-VEGF agent for wet AMD: evaluation of impact on visual acuity, treatment frequency and retinal morphology in a real-world clinical setting.

PURPOSE: The aim of the present cross-sectional real-world study is to evaluate the impact of switch of anti-VEGF agent from ranibizumab to aflibercept on visual acuity, treatment frequency and retinal morphology after 12 months in eyes with ongoing chronic treatment for wet age-related macular degeneration (AMD) compared to eyes not subjected to switch of anti-VEGF agent. METHODS: Data was obtained retrospectively from the Swedish Macular Register, spectral-domain optical coherence tomography (OCT) images and electronic patient charts. All eyes included were treated in the same clinical setting at the Department of Ophthalmology at the county hospital of Västmanland in Västerås, Sweden. RESULTS: In total, 282 and 359 eyes were included in the non-switch and switch cohorts, respectively. The cohorts were well balanced. Visual acuity remained stable during the observation period in both cohorts of eyes. The number of anti-VEGF treatments slowly declined over time in both cohorts of eyes and, consequently, the treatment intervals increased during the observation period. In eyes subjected to switch of anti-VEGF agent, planned treatment interval at 12 months was 7.6 (mean; SD 2.9) weeks compared to 6.8 (mean; SD 2.7) in the non-switch cohort (P = 0.001). OCT images demonstrated lower prevalence of intraretinal and subretinal fluid as well as pigment epithelial detachment at 12 months in eyes subjected to switch of anti-VEGF agent compared to non-switch eyes. CONCLUSION: Switch of anti-VEGF agent from ranibizumab to aflibercept did not affect visual function whereas improvement in retinal morphology was observed. These findings suggest a beneficial effect of switching from ranibizumab to aflibercept in eyes with ongoing chronic anti-VEGF treatment irrespective of previous response to ranibizumab. Longer follow-up is required to further evaluate the potential clinical significance of this finding.

Association of Gastric Bypass Surgery With Risk of Developing Diabetic Retinopathy Among Patients With Obesity and Type 2 Diabetes in Sweden: An Observational Study.

Importance: Knowledge of the incidence and progression of diabetic retinopathy (DR) after gastric bypass surgery (GBP) in patients with obesity and diabetes could guide the management of these patients. Objective: To investigate the incidence of diabetic ocular complications in patients with type 2 diabetes after GBP compared with the incidence of diabetic ocular complications in a matched cohort of patients with obesity and diabetes who have not undergone GBP. Design, Setting, and Participants: Data from 2 nationwide registers in Sweden, the Scandinavian Obesity Surgery Registry and the National Diabetes Register, were used for this cohort study. A total of 5321 patients with diabetes from the Scandinavian Obesity Surgery Registry who had undergone GBP from January 1, 2007, to December 31, 2013, were matched with 5321 patients with diabetes from the National Diabetes Register who had not undergone GBP, based on sex, age, body mass index (BMI), and calendar time (2007-2013). Follow-up data were obtained until December 31, 2015. Statistical analysis was performed from October 5, 2018, to September 30, 2019. Exposure: Gastric bypass surgery. Main Outcomes and Measures: Incidence of new DR and other diabetic ocular complications. Results: The study population consisted of 5321 patients who had undergone GBP (3223 women [60.6%]; mean [SD] age, 49.0 [9.5] years) and 5321 matched controls (3395 women [63.8%]; mean [SD] age, 47.1 [11.5] years). Mean (SD) follow-up was 4.5 (1.6) years. The mean (SD) BMI and hemoglobin A1c concentration at baseline were 42.0 (5.7) and 7.6% (1.5%), respectively, in the GBP group and 40.9 (7.3) and 7.5% (1.5%), respectively, in the control group. The mean (SD) duration of diabetes was 6.8 (6.3) years in the GBP group and 6.4 (6.4) years in the control group. The risk for new DR was reduced in the patients who underwent GBP (hazard ratio, 0.62 [95% CI, 0.49-0.78]; P < .001). The dominant risk factors for development of DR at baseline were diabetes duration, hemoglobin A1c concentration, use of insulin, glomerular filtration rate, and BMI. Conclusions and Relevance: This nationwide matched cohort study suggests that there is a reduced risk of developing new DR associated with GBP, and no evidence of an increased risk of developing DR that threatened sight or required treatment.

Treatment of age-related macular degeneration after cataract surgery: a study from the Swedish National Cataract and Macula Registers.

PURPOSE: To characterize pre- and perioperative factors associated with treatment for wet age-related macular degeneration (wet AMD) after cataract surgery. METHODS: This register-based cohort study with data from the Swedish National Cataract Register (NCR) and the Swedish Macula Register (SMR) from 2010 to 2017 compared eyes with and without preoperative AMD that had undergone cataract surgery and was subsequently treated for wet AMD to eyes not treated within the study period. All first-eye surgeries registered in the NCR from 2010 to 2017 and matching eyes found in the SMR that had undergone treatment for wet AMD ≥ 1 year after the cataract procedure were included. Data for cataract surgery date, age and gender, use of a blue-blocking IOL, preoperative visual acuity, ocular comorbidities, posterior capsule rupture and date of AMD treatment initiation were extracted. RESULTS: The only independent factor associated with postoperative treatment of wet AMD in both groups was female gender (67.3% vs. 58.8%, p < 0.001 and 66.4% vs. 60.6%, p = 0.001, respectively). Older age was an independent factor in eyes without preoperative AMD (78.4 ± 6.5 vs. 73.4 ± 9.6 years, p < 0.001). A blue-blocking IOL appeared to decrease the likelihood of subsequent wet AMD treatment slightly but not statistically significant in eyes with preoperative AMD (52.7% vs. 56.8%, p = 0.110). CONCLUSIONS: Some factors (female gender, high age) are associated with undergoing subsequent treatment for wet AMD to a higher extent. If the use of a blue-blocking IOL offers any protection from undergoing AMD treatment after cataract surgery, such an effect must be very small.

Long-term follow-up of antivascular endothelial growth factor treatment for diabetic macular oedema: a four-year real-world study.

PURPOSE: To evaluate visual acuity (VA) and central retinal thickness (CRT) on optical coherence tomography during a 4-year period in patients treated for sight-threatening diabetic macular oedema (DMO) at two Swedish county hospitals. Additionally, to compare health-related quality of life and subjective visual functioning before and after 4 years of treatment. METHODS: Fifty-eight patients with DMO were evaluated after 4 years of antivascular endothelial growth factor (VEGF) treatment. VA, CRT and clinical data were retrospectively reviewed. Health-related quality of life and subjective visual functioning were evaluated with Short Form Health Survey (SF-36) and National Eye Institute Vision Functioning Questionnaire 25 (VFQ-25). Comparisons between independent groups were performed using Pearson's χ2 test, Fisher's exact test or Mann-Whitney U test. Spearman's ρ was used for correlation analyses. Wilcoxon signed-rank test was used for comparison between dependent groups. Logistic regression analysis was applied for analysis of VA and CRT over 4 years. RESULTS: Follow-up data were obtained from 37 of 58 (63.8%) patients. Baseline characteristics were similar, regardless of follow-up. VA improvement at 1 year (mean + 4.4, SD 7.5; ETDRS letter score) was maintained over 3 years, then declined. CRT was reduced throughout the study. In the first treatment year, eyes received 5.1 (1.4) anti-VEGF injections, followed by approximately two injections yearly. Additional treatment included laser and dexamethasone implants. SF-36 showed no change at 4 years, compared with baseline. VFQ-25 demonstrated improvement in near vision activities (p = 0.036). CONCLUSION: Significant long-term improvement in visual function was present in patients with anti-VEGF-treated DMO.

Better visual outcome at 1 year with antivascular endothelial growth factor treatment according to treat-and-extend compared with pro re nata in eyes with neovascular age-related macular degeneration.

PURPOSE: To evaluate treatment outcome at 12 months in eyes with neovascular age-related macular degeneration (nAMD) treated with antivascular endothelial growth factor (anti-VEGF) injections according to either pro re nata (PRN)- or treat-and-extend (TE)-regimen in one clinical setting in Sweden. METHODS: Data were obtained retrospectively from the Swedish Macula Register, optical coherence tomography-database and electronic patient charts. The study included 443 eyes; 223 PRN- and 220 TE-treated eyes. Baseline (BL) characteristics and follow-up data at 6 and 12 months were collected. Statistical regression analysis was performed to evaluate association between treatment strategy and visual outcome at 12 months. RESULTS: Baseline (BL) characteristics were well balanced between cohorts. Visual acuity at 12 months was higher in TE-cohort 66.5 (13.1) compared to PRN-cohort 60.1 (17.6) (p = 0.000). Visual improvement at 12 months was +5.2 (11.8) and +1.2 (12.7) letters Early Treatment Diabetic Retinopathy Study (ETDRS) in TE- and PRN-cohorts, respectively (p = 0.002). Number of administered injections at 12 months was 10.2 (2.1) and 6.3 (2.1) in the two cohorts (p = 0.000). Statistical analysis demonstrated a strong association between TE treatment strategy and improvement in visual acuity at 12 months. CONCLUSION: Eyes treated according to TE had better visual outcome at 12 months. The results indicate that treatment according to proactive TE-regimen is superior to treatment according to PRN-regimen in clinical routine care of nAMD.

Gastric bypass surgery does not increase the risk for sight-threatening diabetic retinopathy.

PURPOSE: To study the occurrence and level of diabetic retinopathy (DRP) before and after planned bariatric surgery and to investigate potential risk factors for deterioration of DRP. METHODS: The Scandinavian Obesity Surgery Registry (SOReg) was used to identify diabetic patients who underwent gastric bypass (GBP) surgery at three centres in Sweden during 2008-2010. Information regarding DRP screening was obtained from ophthalmological patient charts. Patients who had DRP screening before and after GBP surgery were included in the study. RESULTS: The survey included 117 patients. Mean age was 50 (SD 10) years, body mass index (BMI) 43 (SD 8) kg/m2 and HbA1c 64 (SD 18) mmol/mol before surgery. One year post-GBP, BMI was reduced to 31 (SD 6) kg/m2 . HbA1c was 43 (SD 10) mmol/mol, and in 66% (77/117) treatment for diabetes had been discontinued. Occurrence of DRP before GBP was as follows: no DRP 62%, mild 26%, moderate 10%, severe 0% and proliferative DRP 2%. No significant changes in occurrence of DRP after surgery were observed. Twelve patients (16%) developed mild DRP. In seven patients with pre-existing DRP, deterioration was observed and two of these patients required treatment for sight-threatening DRP. No association between preoperative BMI, HbA1c or reduction in HbA1c and worsening of DRP was found. CONCLUSION: In a majority of patients, no deterioration of DRP following GBP was observed. Screening for DRP before planned surgery is recommended for all diabetic patients about to undergo bariatric surgery to identify any pre-existing DRP.

Treatment for neovascular age-related macular degeneration in Sweden: outcomes at seven years in the Swedish Macula Register.

PURPOSE: To present Swedish Macula Register (SMR) data regarding treatment of neovascular age-related macular degeneration (AMD) in clinical practice since 2008. METHODS: A retrospective register-based study was conducted. Evaluation of baseline demographics, visual outcome and number of injections during this period is presented. RESULTS: Mean age at diagnosis was 79 ± (SD) 8 years; 65% were female. The proportion of patients with <2 months' duration of symptoms increased from 26% in 2008 to 41% in 2014 (p = 0.001). Mean visual acuity (VA) at baseline increased from 54.3 ± 15.0 early treatment diabetic retinopathy study (ETDRS) letters in 2008 to 57.8 ± 15.6 letters in 2014 (CI95 2.6; 4.3; p < 0.001). Mean VA after 1 year of treatment increased from 57.8 ± 17.7 ETDRS letters for patients who started the treatment in 2008 to 62.8 ± 16.4 ETDRS letters in patients starting treatment in 2014 (CI95 2.67; 4.64; p < 0.001). During all study years, the proportion of patients with an improvement in VA of between 5 and 15 letters was around 30%, while 14% had VA improvement of more than 15 letters. The mean number of injections during the first treatment year increased from 4.3 ± 1.9 in 2008 to 5.9 ± 2.9 in 2014 (CI95 1.40; 1.67; p < 0.001). Seven-year follow-up of 322 eyes showed a mean change of -1 letters from baseline, with a mean of 21 injections for the entire period. CONCLUSION: The duration of symptoms before treatment decreased, while VA at baseline and after 1 year of treatment increased over the years and so did the number of injections. Long-term follow-up demonstrated stable VA.

Patient-reported outcomes and visual acuity after 12months of anti-VEGF-treatment for sight-threatening diabetic macular edema in a real world setting.

AIMS: To examine objective visual acuity measured with ETDRS, retinal thickness (OCT), patient reported outcome and describe levels of glycated hemoglobin and its association with the effects on visual acuity in patients treated with anti-VEGF for visual impairment due to diabetic macular edema (DME) during 12months in a real world setting. METHODS: In this cross-sectional study, 58 patients (29 females and 29 males; mean age, 68years) with type 1 and type 2 diabetes diagnosed with DME were included. Medical data and two questionnaires were collected; an eye-specific (NEI VFQ-25) and a generic health-related quality of life questionnaire (SF-36) were used. RESULTS: The total patient group had significantly improved visual acuity and reduced retinal thickness at 4months and remains at 12months follow up. Thirty patients had significantly improved visual acuity, and 27 patients had no improved visual acuity at 12months. The patients with improved visual acuity had significantly improved scores for NEI VFQ-25 subscales including general health, general vision, near activities, distance activities, and composite score, but no significant changes in scores were found in the group without improvements in visual acuity. CONCLUSIONS: Our study revealed that anti-VEGF treatment improved visual acuity and central retinal thickness as well as patient-reported outcome in real world 12months after treatment start.

Reduced occurrence of severe visual impairment after introduction of anti-Vascular Endothelial Growth Factor in wet age-related macular degeneration - a population- and register-based study from northern Sweden.

PURPOSE: To study the occurrence of severe visual impairment (SVI) and treatment outcome at 12 months in patients treated for wet age-related macular degeneration (AMD) by use of data from the Swedish Macula Register (SMR) and referrals to the regional low vision clinics in five northern counties. METHODS: Referrals to low vision clinics during 2005, 2009 and 2013 and treatment outcome at 12 months from the SMR database from 2008 until 2013 in patients >65 years of age in five northern counties were included in the survey. RESULTS: The rate of referral due to AMD was significantly reduced during the time period (-48%; p < 0.001). At 12 months, a significant slight mean improvement in logMAR visual acuity (VA) was observed (-0.01, SD 0.37; p < 0.001) after a mean of 5.0 ± 2.3 anti-vascular endothelial growth factor (VEGF)-injections were administered. Age and low baseline VA was associated with less favourable visual outcome (p < 0.001). CONCLUSION: Referral rate to low vision clinic is a valuable tool for estimating occurrence of SVI and fell between the years 2005 until 2013. Data from the SMR showed improvement in visual acuity on the whole, but also identified patients at high risk for developing SVI during anti-VEGF-treatment.

Visual functioning and health-related quality of life in diabetic patients about to undergo anti-vascular endothelial growth factor treatment for sight-threatening macular edema.

PURPOSE: To examine patient-reported outcome (PRO) in a selected group of Swedish patients about to receive anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular edema (DME). MATERIAL AND METHODS: In this cross-sectional study, 59 patients with diabetes mellitus, who regularly visited the outpatient eye-clinics, were included. Sociodemographic and clinical data were collected and the patients completed PRO measures before starting anti-VEGF treatment. PRO measures assessed eye-specific outcomes (NEI-VFQ-25) and generic health-related quality of life (SF-36). RESULTS: The participants consisted of 30 men and 29 women (mean age, 68.5years); 54 (92%) patients had type 2 diabetes; 5 (9%) patients had moderate or severe visual impairment; 28 (47%) were classified as having mild visual impairment. Some of the patients reported overall problems in their daily lives, such as with social relationships, as well as problems with impaired sight as a result of reduced distance vision. CONCLUSIONS: Further studies are needed to investigate PRO factors related to low perceived general health in this patient population. It is important to increase our understanding of such underlying mechanisms to promote improvements in the quality of patient care.