The Patient Voice in Neovascular Age-Related Macular Degeneration: Findings from a Qualitative Study.

INTRODUCTION: Visual impairment resulting from diseases such as neovascular age-related macular degeneration (nAMD) may cause behavioural, environmental, psychological, and logistical challenges that could act as barriers to effective uptake and sustainability of treatment with anti-vascular endothelial growth factor agents (anti-VEGFs). Understanding emotions and experiences of patients with nAMD may help inform the determinants of adherence, and could contribute to improvements in ophthalmic outcomes and quality of life. METHODS: Seventeen patients with nAMD receiving anti-VEGF injections were enrolled from three clinics: one each in France (n = 5), Germany (n = 6), and the UK (n = 6). Patients' health information and treatment characteristics were collected. Individual phone interviews were conducted by experienced health care interviewers. Transcripts were analysed thematically. RESULTS: Patients (53% female) had a mean age of 77 years. Bilateral anti-VEGF injections were received by 24% (n = 4); and most (76%, n = 13) were adherent to their treatment. Patient emotions at diagnosis ranged from happiness at learning about the treatment for nAMD to being terrified of receiving an injection in the eye. Most patients mentioned feeling anxious and fearful before their first injection despite receiving reassurance. After the first injection, these feelings and apprehension abated for many, but not all. With the goal of maintaining the best possible vision, few (24%, n = 4) patients reported more than one missed appointment, and most had never considered stopping treatment. No patient reported additional assistance beyond family support; however, many had difficulties with recreational and domestic activities and had developed coping strategies. CONCLUSION: This study provides insights on patients' emotions related to their experience of nAMD and its management, highlighting the varying experiences between individuals. It shows the importance of the patient's voice when considering patient care and management, and how the nature and timing of interventions can improve the experience of living with and managing nAMD.

Neovascular age-related macular degeneration (nAMD), also known as wet age-related macular degeneration (wAMD), is an eye condition that is a common cause of vision loss and worsens over time without treatment. This condition mainly occurs in people aged 70 years or older. The standard of care is an injection of anti-vascular endothelial growth factor (anti-VEGF) into the eye to minimise vision loss that continues over time without treatment. To maximise the benefits of treatment, injections are required at regular intervals over time. The purpose of this study was to understand the emotions and experiences of patients with nAMD about their disease, its consequences, and its management. Seventeen patients from three countries (France, Germany, and the UK) were interviewed over the telephone. Patients reported diverse feelings and responses to their disease and treatment. Many felt nervous and anxious at diagnosis and before their first injection (despite reassurances from their doctors); however, after the first injection, these feelings and apprehension abated for many, but not all. Most patients (76%) missed fewer than two appointments in the past year, and almost all (82%) did not consider stopping treatment. Patients learned to deal with their nAMD, but many had difficulties with daily activities. Patients developed ways to manage tasks such as cooking, cleaning, knitting, and driving. The insights from this study help understand how care for patients with nAMD can be improved by addressing patients' concerns and feelings about their disease and treatment.

Defining Nonadherence and Nonpersistence to Anti-Vascular Endothelial Growth Factor Therapies in Neovascular Age-Related Macular Degeneration.

Importance: Poor adherence or persistence to treatment can be a barrier to optimizing clinical practice (real-world) outcomes to intravitreal injection therapy in patients with neovascular age-related macular degeneration (nAMD). Currently, there is a lack of consensus on the definition and classification of adherence specific to this context. Objective: To describe the development and validation of terminology on patient nonadherence and nonpersistence to anti-vascular endothelial growth factor therapy. Design, Setting, and Participants: Following a systematic review of currently used terminology in the literature, a subcommittee panel of retinal experts developed a set of definitions and classification for validation. Definitions were restricted to use in patients with nAMD requiring intravitreal anti-vascular endothelial growth factor therapy. Validation by the full nAMD Barometer Leadership Coalition was established using a modified Delphi approach, with predetermined mean scores of 7.5 or more signifying consensus. Subsequent endorsement of the definitions was provided from a second set of retinal experts, with more than 50% members agreeing or strongly agreeing with all definitions. Main Outcomes and Measures: Development of consensus definitions for the terms adherence and persistence and a classification system for the factors associated with treatment nonadherence or nonpersistence in patients with nAMD. Results: Nonadherence was defined as missing 2 or more treatment or monitoring visits over a period of 12 months, with a visit considered missed if it exceeded more than 2 weeks from the recommended date. Nonpersistence was defined by nonattendance or an appointment not scheduled within the last 6 months. The additional terms planned discontinuation and transfer of care were also established. Reasons for treatment nonadherence and nonpersistence were classified into 6 dimensions: (1) patient associated, (2) condition associated, (3) therapy associated, (4) health system and health care team associated, (5) social/economic, and (6) other, with subcategories specific to treatment for nAMD. Conclusions and Relevance: This classification system provides a framework for assessing treatment nonadherence and nonpersistence over time and across different health settings in the treatment of nAMD with current intravitreal anti-vascular endothelial growth factor treatments. This may have additional importance, given the potential association of the coronavirus pandemic on adherence to treatment in patients with nAMD.

Fluid as a critical biomarker in neovascular age-related macular degeneration management: literature review and consensus recommendations.

Current guidelines on the management of patients with neovascular age-related macular degeneration (nAMD) lack clear recommendations on the interpretation of fluid as seen on optical coherence tomography (OCT) imaging and the incorporation of this information into an ongoing disease treatment strategy. Our objective was to review current guidelines and scientific evidence on the role of fluid as a biomarker in the management of nAMD, and develop a clinically oriented, practical algorithm for diagnosis and management based on a consensus of expert European retinal specialists. PubMed was searched for articles published since 2006 relating to the role of fluid in nAMD. A total of 654 publications were screened for relevance and 66 publications were included for review. Of these, 14 were treatment guidelines, consensus statements and systematic reviews or meta-analyses, in which OCT was consistently recommended as an important tool in the initial diagnosis and ongoing management of nAMD. However, few guidelines distinguished between types of fluid when providing recommendations. A total of 52 publications reported primary evidence from clinical trials, studies, and chart reviews. Observations from these were sometimes inconsistent, but trends were observed with regard to features reported as being predictive of visual outcomes. Based on these findings, diagnostic recommendations and a treatment algorithm based on a treat-and-extend (T&E) regimen were developed. These provide guidance on the diagnosis of nAMD as well as a simple treatment pathway based on the T&E regimen, with treatment decisions made according to the observations of fluid as a critical biomarker for disease activity.

Real-World Visual and Neovascularisation Outcomes from anti-VEGF in Central Retinal Vein Occlusion.

PURPOSE: Central retinal vein occlusion (CRVO) can be complicated by macular oedema, requiring intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF). CRVO can cause neovascularisation, potentially causing persistent pain if not identified early. Whilst clinical trial data describe visual and anti-neovascular benefit from anti-VEGF there are limited real-world data. METHODS: A retrospective cohort study of a consecutive series of patients found from a review of the electronic medical record at a single UK centre. Visual acuity, macula status, number of IVIs and neovascular status were extracted at standardised timepoints. RESULTS: In total, 231 eyes from 231 patients were identified with 6-48 months of follow up. Twenty-four months after treatment initiation, 81 eyes (53.3%) had no remaining macula oedema and mean visual acuity gained was 8.9 (SD 19.0) Early Treatment of Diabetic Retinopathy Study (ETDRS) letters following a mean of 10.1 (3.9) IVIs. Of 222 eyes that had no initial neovascularisation, 11 went on to develop it, with iris involvement in 10 eyes. Median time from treatment initiation to neovascularisation was 17.2 (range 5.0-44.1) months, and the median time from latest IVI to neovascularisation was 9.6 (2.9-27.6) months after a median of 4 (3-10) IVIs. CONCLUSIONS: Visual acuity in CRVO complicated by macular oedema improves following anti-VEGF treatment but real-world gains are more modest than those from clinical trials. Neovascularisation following CRVO can be substantially delayed by anti-VEGF treatment and so if individuals who have received IVIs are to be effectively screened for neovascularisation long-term surveillance is necessary.

Nonadherence or Nonpersistence to Intravitreal Injection Therapy for Neovascular Age-Related Macular Degeneration: A Mixed-Methods Systematic Review.

TOPIC: Systematic review of risk factors for nonadherence and nonpersistence to intravitreal anti-vascular endothelial growth factor (VEGF) injection therapy for neovascular age-related macular degeneration (nAMD). CLINICAL RELEVANCE: Lack of adherence (nonadherence) or undertreatment (nonpersistence) with respect to evidence from clinical trials remains a significant barrier to optimizing real-world outcomes for patients with nAMD. Contributing factors and strategies to address this are poorly understood. METHODS: Studies that reported factors for nonadherence and nonpersistence to anti-VEGF therapy as well as studies examining strategies to improve this were included. Trial eligibility and data extraction were conducted according to Cochrane review methods. Risk of bias was assessed using the Mixed Method Assessment Tool and certainty of evidence evaluated according to the GRADE Confidence in the Evidence from Reviews of Qualitative Research tool. Data were collated descriptively. RESULTS: Of the 1284 abstract results screened, 124 articles were assessed in full and 37 studies met the inclusion criteria. Definitions of nonadherence and nonpersistence varied or were not reported. Nonpersistence occurred early, with up to 50% of patients stopping treatment by 24 months. High rates of nonadherence were similarly reported, occurring in 32% to 95% of patients. Certainty of this finding was downgraded to a moderate level because of the heterogeneity in definitions used across studies. Multiple factors determine nonadherence and nonpersistence, including at the condition, therapy, patient, social/economic, and health systems/healthcare team levels. Moderate quality evidence points to lower baseline vision and poorer response to treatment as condition-related variables. The effects of other factors were of lower certainty, predominantly due to small numbers and potential biases in retrospective assessment. Although many factors are not modifiable (e.g., patient comorbidity), other factors are potentially correctable (e.g., lack of transport or mismatched patient expectations). Evidence on strategies to improve adherence and persistence is limited, but where available, these have proven effective. CONCLUSIONS: Awareness of factors related to poor patient adherence and persistence in nAMD could help identify at-risk populations and improve real-world outcomes. Further work is required to develop uniform definitions and establish high-quality evidence on interventions that can be easily implemented.

Randomised trial of wide-field guided PRP for diabetic macular oedema treated with ranibizumab.

BACKGROUND: Diabetic macular oedema (DMO) is effectively treated with ranibizumab but multiple injections are required. Where there is also peripheral ischaemia, it has been promoted that targeted panretinal photocoagulation (PRP) may reduce the number of injections. METHOD: Patients with optical coherence tomography confirmed DMO and Ultra-widefield Fundus Fluorescein Angiography confirmed peripheral retinal ischaemia were randomised to PRP plus ranibizumab or ranibizumab monotherapy. After three injections, repeat injections were given until the visual acuity was stable and the macula was dry. Re-treatment was given if there was a drop of visual acuity and/or a recurrence of intra-retinal fluid. The primary outcome was the number of repeat injections required after the first 6 months up until 1 year. RESULTS: There were 49 patients, 25 in the ranibizumab only group and 24 in the ranibizumab + PRP group recruited at seven UK sites. The average number of injections in the ranibizumab-only arm was 6.84 over 1 year and 2.52 between months 6 and 12. The average number of injections in the combined arm was 6.67, with the number of injections in the second 6 months 1.92. For the primary outcome, comparing the number of 6- to 12-month injections, the result was not statistically significant (p = 0.33). CONCLUSION: The addition of targeted PRP to areas of non-perfusion in a patient with DMO does not reduce the number of injections required in the first year. It seems most likely that local VEGF at the macula is the main cause of DMO.

Expanding the role of medical retina virtual clinics using multimodal ultra-widefield and optical coherence tomography imaging.

BACKGROUND: An increasingly elderly population with a corresponding increase in ophthalmic conditions has led to increased pressure on hospital eye services (HES). In this study, we evaluated the use of a medical retina virtual clinic (MRVC), which has expanded into assessing all new medical retina referrals, where the need for urgent treatment was not clear. METHODS: Retrospective analysis of all new patients who were seen in the MRVC between April 2016 and May 2018. Pro forma sheets were used in the MRVC to record the patient history, visual acuity, and type of imaging required. Two consultants reviewed the completed pro formas and images and provided a final diagnosis and management plan. These results and reasons for face-to-face (F2F) clinic appointment requests were analyzed. RESULTS: Six hundred ten new referrals were enrolled in the virtual clinic. The most common diagnosis was diabetic eye disease (59.9%). In the virtual clinic 44.1% were followed up, 28.1% were discharged, and 27.8% were booked an F2F clinic appointment (urgent/routine). The main reason for F2F clinic was to offer treatment. Urgent F2F appointments took place on average 11.9 days after virtual clinic attendance. In only two cases was the image quality felt to be inadequate to assess the retina. CONCLUSIONS: MRVC is an effective way of triaging medical retina referrals to allow those patients needing treatment to be seen promptly in the medical retinal service. The use of multimodal ultra-widefield and optical coherence tomography imaging allows assessment of a wide range of retinal pathologies and is a promising solution to alleviate the burden on HES.

Measuring the benefit of 4 years of intravitreal ranibizumab treatment for neovascular age-related macular degeneration.

AIM: To analyse the benefit of intravitreal ranibizumab over 4 years for patients with neovascular age-related macular degeneration (AMD). METHODS: A retrospective case note review of all patients who started treatment between August 2007 and September 2009 in our unit, minimum follow-up 2 years, maximum 4 years. The main outcome measures were: numbers of patients with different levels of vision, changes in visual acuity, number of treatments and numbers remaining under follow-up. RESULTS: 1086 eyes of 1017 patients received treatment. Numbers of patients remaining under follow-up were 892/1017 (87.71%) at 12 months, 730/1017 (71.78%) at 24 months, 468/730 (64.11%) at 36 months and 110/217 (50.69%) at 48 months. The main reasons for patients no longer being under follow-up were the consequences of old age or transfer of care. 50% of patients had 6/18 or better over 4 years. Patients received on average 5.79 ± 2.53, 9.15 ± 3.79, 11.22 ± 4.92 and 13.7 ± 7.84 injections by 12, 24, 36 and 48 months, respectively. CONCLUSIONS: We suggest that the numbers of patients with a particular level of vision may best reflect the actual benefit of AMD treatment provided by a service. Long-term follow-up is required as only 72/730 (10%) had been discharged at 36 months, half of whom had good vision of greater than 60 letters. 83% and 65% of patients needed treatment in the third and fourth year. Follow-up may be for the rest of the patients' life or at some point they may no longer be well enough to attend.

Anatomical and visual outcome of retinal angiomatous proliferation treated with photodynamic therapy and intravitreal triamcinolone.

PURPOSE: To evaluate the efficacy and safety of photodynamic therapy (PDT) with verteporfin combined with intravitreal triamcinolone (TA) in retinal angiomatous proliferation (RAP). DESIGN: Retrospective, consecutive, noncomparative case series. METHODS: Patients newly diagnosed with RAP underwent indocyanine green angiography (ICGA)-guided PDT with verteporfin, immediately followed by intravitreal TA. Complete ocular examination, fluorescein angiography (FA), ICGA, and optical coherence tomography (OCT) were performed at baseline and follow-up visits every three months. RESULTS: Seventeen eyes of seventeen patients underwent this simultaneous combined treatment. All patients had 12 months of follow-up. Complete resolution of angiographic leakage was achieved in 83% at 12 months. Visual acuity improved in 35%, and was stable in 47%. Eleven patients developed recurrent leakage after six to 12 months, which settled completely after repeat combined treatment. CONCLUSIONS: This simultaneous combined treatment in patients with RAP was effective in reducing or eliminating retinal edema, regression of neovascularization, and stabilizing or improving visual acuity.