3.1 Physician Characteristics

Of the 4715 ophthalmologists invited to participate, 454 completed the survey and were included in the analysis (Fig. 1), making the overall response rate 9.6%. The participants in wave 2 included new participants (n = 347, 76%) as well as participants who had completed the wave 1 survey (n = 107, 24%) to reach the desired sample size. The majority of participants specialized in treatment of the retina (63%) and/or general ophthalmology (57%) (Table 1). Most practiced in hospital (74%) and/or were in office-based (31%) settings and reported having treated patients for 6–10 years (23%), 11–15 years (21%), or 16–20 years (20%). Approximately two-thirds (67%) were male, and more than half (60%) were aged 40–59 years, while 27% were younger than 40 years of age.

Fig. 1

Distribution of physicians invited to participate

Table 1 Physician characteristics (N = 454)

Per the screening criteria, all participants had prescribed (94%) and/or administered (78%) IVT-AFL in the past 6 months for indications including neovascular age-related macular degeneration (nAMD; 93%), visual impairment due to diabetic macular edema (81%), macular edema secondary to central (72%) or branch retinal vein occlusion (67%), and myopic choroidal neovascularization (50%) (see Table B1 in Appendix B of the ESM). Approximately half reported administering an average of 5–40 anti-VEGF injections per month (44%) and 5–40 IVT-AFL injections per month (53%); 76% had administered their last IVT-AFL injection < 1 month prior to completing the study survey (Table B1 in the ESM).

3.2 Physician Knowledge3.2.1 Storage and Preparation

Participants were asked seven true/false questions related to the storage and preparation of IVT-AFL (Fig. 2). Ninety-two percent correctly responded that adequate anesthesia and asepsis must be provided for the patient; 85% correctly indicated that IVT-AFL must be stored in the refrigerator.

Fig. 2

Storage and preparation of IVT-AFL (Questions 1a, 1c, 1e, 1g, 1h, 1i, 1k) [N = 454]. IVT-AFL intravitreal aflibercept. For each of the following statements related to the storage and preparation of Eylea, please indicate if the statement is true, not true, or if you do not know

3.2.2 Dosing

Three questions were asked about IVT-AFL dosing. Most participants (82%) correctly reported that the vial contains more than the recommended dose and excess volume should be expelled before injecting (Table 2). Likewise, 78% correctly reported that 50 μL (2 mg) is the recommended dose (Table 3). A lower percentage of participants (58%) correctly reported that after removing all drug from the vial with a syringe, the plunger should be depressed until the tip aligns with the line that marks 0.05 mL on the syringe (Table 2).

Table 2 Excess volume of IVT-AFL (N = 454)Table 3 Recommended dose of IVT-AFL (N = 454)3.2.3 Safe Use

The survey included five questions about safe use. More than three-quarters of participants (78%) correctly identified all three contraindications for IVT-AFL (Fig. 3). Correct responses ranged from 82% for ‘Patients with active severe intraocular inflammation’ as a contraindication, to 92% for ‘Patients with a known hypersensitivity to the active substance aflibercept or to any of the excipients (e.g., nonactive ingredients)’. Overall, 94% of participants correctly indicated that they should ‘Inform the patient to report any signs and symptoms potentially associated with serious adverse events (AEs) and provide information on when to seek medical attention, when preparing a patient to start IVT-AFL treatment’; 90% selected ‘Explain the implications of anti-VEGF treatment’, and 67% selected ‘Provide the Patient Booklet, which includes a patient booklet audio CD and patient information leaflet’ (Fig. B1 in Appendix B of the ESM). Slightly more than half of physicians (53%) selected the correct timeframe for which women of childbearing potential must use effective contraception during treatment and for at least 3 months after the last IVT-AFL injection, while 28% incorrectly indicated that IVT-AFL should never be used in pregnancy. More than three-quarters (76%) correctly indicated that IVT-AFL is not recommended for women who are breastfeeding (Figs. B2 and B3 in Appendix B of the ESM).

Fig. 3

Contraindications for IVT-AFL (Question 11) [N = 454]. IVT-AFL intravitreal aflibercept. Eylea is contraindicated in which of the following patients? Tick all that apply

3.2.4 Injection Procedure

A series of six questions was asked about proper injection procedure (Fig. B4 in Appendix B of the ESM); 92% of participants correctly responded ‘True’ to a true/false question asking whether disinfectant (e.g., povidone iodine solution) should be applied to the periocular skin, eyelid, and ocular surface, and 89% correctly responded that topical anesthesia should be used prior to injection. When asked to identify steps that should be taken prior to marking the scleral injection site, 84% correctly selected ‘Cover the eye with a sterile drape’, and 76% correctly selected ‘Insert a sterile lid speculum’. Most participants correctly reported that the injection needle should be inserted into the vitreous cavity, avoiding the horizontal meridian, and aiming toward the center of the globe (80%), and that in preparation for the injection, the eye should be marked at a distance of 3.5–4.0 mm posterior to the limbus (77%).

3.2.5 Possible Adverse Effects

Two questions examined post-injection monitoring (Fig. B5 in Appendix B of the ESM). Most participants (83%) correctly responded that increased intraocular pressure has been observed within 60 min of intravitreal injection. When shown a list of potential known undesirable adverse effects, participants correctly selected endophthalmitis (91%), transient increase of intraocular pressure (92%), retinal tear or retinal detachment (70%), and cataract (traumatic, nuclear, subcapsular, cortical) or lenticular opacities (69%) (Fig. B6 in Appendix B of the ESM).

3.3 Receipt and Use of Educational Materials

Rates of self-reported receipt of the materials were relatively high (Table 4): 89% reported receiving the SmPC, 82% received the Eylea Prescriber Guide, 65% received the Indication-Specific Patient Booklet (including a patient information audio CD and the patient information leaflet), and 54% received the Intravitreal Injection Procedure Video. Of those who reported having received the materials, 83% reported having reviewed the SmPC, 82% reviewed the Prescriber Guide, 70% reviewed the patient information and CD, and 72% reviewed the Injection Procedure Video.

Table 4 Receipt and review of IVT-AFL materials (N = 454)

Participants were asked to rate the materials they reviewed on a scale from 1 (not at all helpful) to 4 (extremely helpful). Overall, 73–85% of participants rated all educational materials 3 or 4. When asked how many patients under their care who were receiving IVT-AFL injections were provided the Eylea Patient Booklet, 37% reported that they provided the booklet to all of their patients, and 24% reported providing it to most patients (Table B2 of Appendix B in the ESM). The most common reasons given not to provide the booklet were 'I provide the same information from the Eylea Patient Booklet to patients verbally and give them the chance to ask questions' (46%), 'I did not receive enough copies of the Eylea Patient Booklet to distribute to all my Eylea patients' (38%), and 'I provide alternate materials (e.g., treatment consent form)' (35%).

3.4 Other Analyses3.4.1 Stratified Analyses

Knowledge questions were stratified by subspecialty and average number of monthly IVT-AFL injections. Self-identified retina specialists had the highest proportion of correct responses on all knowledge questions. Ophthalmologists who performed more IVT-AFL injections per month consistently provided more correct responses than those who performed fewer injections. Both sets of stratified knowledge questions can be found in Appendix C of the ESM.

3.4.2 Comparison of Results Across Waves

While ophthalmologists participating in waves 1 and 2 had broadly similar demographic and clinical characteristics and experience with prescribing IVT-AFL, a notably lower proportion of ophthalmologists selected retina as their specialty in wave 2 (63%) than in wave 1 (74%). Reported rates of having received the educational materials were similar among wave 1 participants (range, 50% for the Intravitreal Injection Procedure Video to 87% for the SmPC) and wave 2 participants (range, 54% for the Intravitreal Injection Procedure Video to 89% for the SmPC) (Table 4), as were reported rates of having reviewed the materials among those who had received them (ranges, 67% for the Intravitreal Injection Procedure Video to 89% for the SmPC for wave 1; 70% for the Patient Booklet to 83% for the SmPC for wave 2) (Table 4). On average, results on knowledge questions were similar across waves, except the percentages of correct responses for some questions were slightly higher in wave 1 than in wave 2, with + 5% to 6% differences.

Knowledge about the use of IVT-AFL in women of childbearing potential was similar across waves: 48% of participants in wave 1 and 53% in wave 2 knew that effective contraception must be used during and up to 3 months after treatment. Similar proportions (27% in wave 1 and 28% in wave 2) indicated that IVT-AFL should not be used during pregnancy. In wave 2, 76% of participants responded correctly that IVT-AFL is not recommended for use in women who are breastfeeding; the wave 1 physician survey did not specifically address use of IVT-AFL in breastfeeding women.

Regarding procedural steps, 28% of participants in wave 1 and 22% in wave 2 responded incorrectly that eye dilation is necessary prior to injection. The most common reasons for this response in wave 2 were ‘Eye dilation is done for regular assessment of the underlying disease or other assessments (e.g., fundus examination)’ (58%), ‘Requirements/recommendations by national or local guidelines for intravitreal injections, local protocols, or other recommendations’ (54%), and ‘Personal preference’ (41%). Most participants from both waves (82% in wave 1 and 83% in wave 2) knew that a vial of aflibercept should not be used for more than one patient, as 84% from wave 2 indicated that they knew that drawing multiple injections from the same vial could lead to contamination and subsequent infection.

Knowledge of evaluation of adverse effects was similar across waves. A majority of participants knew that evaluating vision after the injection was done ‘By hand movements or counting fingers’ (wave 1, 60%; wave 2, 54%) and that they needed to ‘Ensure that sterile equipment is available to perform paracentesis if necessary’ if there was increased intraocular pressure following an injection (wave 1, 65%; wave 2, 56%). Finally, on almost all of the questions, physicians in the wave 2 survey who had participated in the wave 1 survey had higher correct response proportions than those who were participating in the survey for the first time; however, the differences between the two groups were 10% or less for two-thirds of the questions.