Quantifying burden of intravitreal injections: questionnaire assessment of life impact of treatment by intravitreal injections (QUALITII).

AIM: To quantify the areas of burden experienced by patients requiring repeated intravitreal injections (IVI) in the management of exudative retinal diseases. METHODS: The validated Questionnaire to Assess Life Impact of Treatment by Intravitreal Injections survey was administered to patients at four retina clinical practices across four US states. The primary outcome measure was Treatment Burden Score (TBS), a single score assessing overall burden. RESULTS: Of 1416 (n=657 age-related macular degeneration; n=360 diabetic macular oedema/diabetic retinopathy; n=221 retinal vein occlusion; n=178 other/uncertain) patients, 55% were women with an average age of 70 years. Patients most frequently reported receiving IVI every 4-5 weeks (40%). The mean TBS was 16.1±9.2 (range 1-48; scale of 1-54), and the TBS was higher in patients with diabetic macular oedema and/or diabetic retinopathy (DMO/DR) (17.1) compared with those with age-related macular degeneration (15.5) or retinal venous occlusive (15.3) (p=0.028). Though the mean level of discomfort was quite low (1.86) (scale 0-6), 50% of patients reported experiencing side effects more than half of the visits. Patients having received fewer than 5 IVI reported higher mean anxiety levels before (p=0.026), during (p=0.050) and after (p=0.016) treatment compared with patients having received more than 50 IVI. After the procedure, 42% of patients reported restrictions from usual activities due to discomfort. Patients reported a high mean satisfaction rating of 5.46 (scale 0-6) with the care of their diseases. CONCLUSIONS: The mean TBS was moderate and highest among patients with DMO/DR. Patients with more total injections reported lower levels of discomfort and anxiety but higher disruption to daily life. Despite the challenges related to IVI, the overall satisfaction with treatment remained high.

Retinal vascular bed area on ultra-wide field fluorescein angiography indicates the severity of diabetic retinopathy.

AIMS: To quantify retinal vascular bed area (RVBA) in square millimetres on stereographically projected ultra-wide field (UWF) fluorescein angiography (FA) in eyes with diabetic retinopathy (DR). METHODS: A prospective, observational study. Baseline Optos 200Tx UWF FA images of 80 eyes with DR from the DAVE (NCT01552408) and RECOVERY (NCT02863354) studies were stereographically projected at the Doheny Image Reading Center to adjust for peripheral distortion. The early-phase FA frame was used to extract the retinal vasculature as a mask for calculating RVBA. The pixels of the retinal vasculature were automatically computed in square millimetres using manufacturer-provided software. RESULTS: Eighteen of 80 diabetic eyes were excluded because image quality and contrast were insufficient for automatic extraction of the retinal vasculature from the background fluorescence. The remaining 62 eyes were included in the final analysis. In comparison with age-matched and sex-matched normal controls, eyes with DR had a higher global RVBA for the entire retina (p<0.001), and RVBA correlated with DR severity (p<0.001), with a higher RVBA in eyes with proliferative DR (66.1±16.2 mm2) than in those with non-proliferative DR (56.2±16.6 mm2) or in normal controls (37.2±9.9 mm2). This tendency was also present in the posterior retina and mid-periphery but absent in the far-periphery. RVBA did not correlate with retinal ischaemia (p>0.05). CONCLUSIONS: Eyes with DR harboured a larger global RVBA for the entire retina than normal controls, and RVBA appeared to indicate DR severity. However, this biomarker was not observed to be a good indicator of retinal ischaemia.

Questionnaire to Assess Life Impact of Treatment by Intravitreal Injections (QUALITII): Development of a patient-reported measure to assess treatment burden of repeat intravitreal injections.

OBJECTIVE: To understand patient burden of treatment of repeated intravitreal injections (IVI) in the management of exudative retinal diseases. METHODS AND ANALYSIS: Participants were sampled from a large urban retina specialty practice in Houston, Texas, USA, based on history of ongoing receipt of IVI. The 50-item Questionnaire to Assess Life Impact of Treatment by Intravitreal Injections questionnaire was developed to evaluate the patient experience including discomfort, anxiety, inconvenience and satisfaction. Categorial principal components analysis (CATPCA) was performed to assess construct validity and internal consistency. A subset of these items was used to establish a measure of total treatment burden, referred to as the IVI Treatment Burden Score (TBS). RESULTS: 142 patients participated in this study. CATPCA analysis revealed five dimensions of patient burden: disruption of normal routine or capacity, anxiety, frequency of visits, chronicity of disease and perceived treatment value or satisfaction. Together, these dimensions accounted for 67% of variance explained. Cronbach's alpha was 0.97. The most frequently cited cause of discomfort was the feeling after anaesthetic wore off. The most common source of anxiety was fear of injection and associated discomfort or pain. Regarding inconvenience, patients reported temporary postinjection debilitation, requiring an average of 8 hours for recovery per treatment. The most frequently identified sources of satisfaction were confidence in the provider or treatment and interactions with staff. CONCLUSIONS: Understanding and quantifying the patient burden associated with repeated IVI for exudative retinal diseases can reveal opportunities to improve delivery methods. The TBS could serve to inform strategies to maximise treatment adherence and optimise patient experiences.

Longitudinal panretinal microaneurysm dynamics on ultra-widefield fluorescein angiography in eyes treated with intravitreal aflibercept for proliferative diabetic retinopathy in the recovery study.

BACKGROUND/AIMS: Quantifying microaneurysms (MAs) turnover may be an objective measure for therapeutic response in diabetic retinopathy. This study assesses changes in MA counts on ultra-widefield fluorescein angiography (UWFA) in subjects undergoing treatment with intravitreal aflibercept injection (IAI) for proliferative diabetic retinopathy (PDR) in the Intravitreal Aflibercept for Retinal Non-Perfusion in Proliferative Diabetic Retinopathy(RECOVERY) study using an automated MA detection platform. METHODS: RECOVERY is a prospective study that enrolled 40 subjects with PDR randomised 1:1 to receive 2 mg IAI every 4 weeks(q4wk) or every 12 weeks (q12wk). UWFA images were obtained at baseline, 6 months and 1 year. Images were analysed using an automated segmentation platform to detect and quantify MAs. Zones 1, 2 and 3 correspond to the macula, mid-periphery and far-periphery, respectively. RESULTS: The q4wk cohort demonstrated a significant decline in MAs in all zones and panretinally at baseline versus month 6, baseline versus year 1, and month 6 versus year 1 (-20.0% to -61.8%; all p<0.001). In the q12wk cohort, baseline versus month 6 showed a significant decline panretinally (mean: -34.2%; p<0.001) and in zone 3 (mean -44.18%; p<0.001). Addiitonally, baseline to year 1 in the q12wk group demonstrated significant decline panretinally (mean: -47.7%; p<0.001) and in zone 3 (mean: -59.8%; p<0.001). All zones demonstrated significantly decline from month 6 to year 1 in the q12wk group. CONCLUSION: Therapy with IAI demonstrates significantly reduced panretinal MA counts in PDR at 1 year in both treatment groups. The use of automated platforms to detect and quantify MAs may provide a novel imaging marker for evaluating disease activity and therapeutic impact. TRIAL REGISTRATION NUMBER: NCT02863354.

Changes in retinal ischaemic index correlate with recalcitrant macular oedema in retinal vein occlusion: WAVE study.

AIM: To evaluate changes in the ischaemic index (ISI) after targeted retinal photocoagulation (TRP) and to investigate the correlation between these changes and macular oedema (ME). METHOD: Twenty-four eyes of 24 patients with retinal vein occlusion (RVO) with recurrent ME were included. Ultra-widefield fluorescein angiography (UWFFA; Optos 200Tx) was obtained at baseline and every 4 months. The regions of retinal non-perfusion and the total gradable retina were manually segmented on UWFFA images for calculating the global ISI. ISI was also computed for specific regions defined by a standardised grid: perimacular area (PMA), near-peripheral area (NPA), mid-peripheral area (MPA) and far-peripheral area (FPA). Global and regional ISIs and change in ISI over time were correlated with central macular thickness (CMT). RESULTS: The ISIs of entire retina, PMA, NPA, MPA and FPA at baseline were 30.5%±23.3, 17.7%±20.6, 21.9%±19.0, 33.0%±27.9 and 48.0%±32.9, respectively. The ISIs at final follow-up were 23.5%±19.9, 15.7%±22.2, 16.5%±16.7, 24.7%±24.7 and 24.7%±24.7, respectively. A significant correlation was found between CMT and global ISI during follow-up (r=0.22, p=0.03). Among the different retinal zones, PMA showed a correlation with CMT (r=0.27, p=0.007). The change in ISI for the total retina (Δtotal), PMA (ΔPMA) and NPA (ΔNPA) retinal regions was positively correlated with the change in CMT (ΔCMT) (r=0.45, 0.42 and 0.50, respectively, p=0.006, 0.009 and 0.002, respectively). CONCLUSION: The severity of ME was correlated with the ISIs of the entire retina and the PMA. The reduction in ME was correlated with the reduction in ISI of the entire retina as well as the ISIs for the NPA and PMA following TRP. The role of TRP, particularly to these regions (NPA, PMA), warrants further investigation in recalcitrant RVO-associated ME.