Investigation of pain and discomfort associated with anti-VEGF injections

Intravitreal injection of anti-vascular endothelial growth factors (VEGF) is the only current treatment for neovascular age-related macular Degeneration (AMD) but necessitates ongoing patient adherence with recuring injections to be effective. Furthermore, AMD itself poses a significant social and economic burden, as the population ages. Patient experience is one of the central pillars of the patient journey. Ocular pain is arguably one of the most common outcomes that affects the patient experience during intravitreal injections, with post-injection experiences and patient adherence to treatment remaining relatively underexplored. Thus, improving the understanding of factors associated with pain and using this to inform pain management strategies in ophthalmic care can drive quality improvement to enhance the patient experience. 
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\nThe aim of the work presented in this thesis was to describe the experiences of patients undergoing anti-VEGF injections associated with pain and the impact on patient adherence and wellbeing, and to explore the factors that contribute to pain.
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\nAn exploratory sequential mixed methods study was undertaken involving semi-structured face-to-face interviews (n=14 individuals with neovascular AMD, n=7 healthcare practitioners), followed by a quantitative phase utilising questionnaires and measurement of electrodermal activity (n=65 individuals with neovascular AMD). The findings from initially exploring the patient experiences associated with the intravitreal treatment using thematic analysis, were apprehension, a dull-aching and sharp pain during injection, and prolonged soreness and irritation of up to 36 hours post-injection affecting their sleep and recovery. Building on the qualitative outcomes, questionnaires were then used to assess pain (Short-Form McGill Pain Questionnaire, SF-MPQ; Visual Analogue Scale, VAS), anxiety (State-Trait Anxiety Inventory) and wellbeing (Warwick-Edinburgh Mental Wellbeing Scale) at baseline, and at 1-2 hours and 24 hours post-treatment. A physiological measure, EDA (electrodermal activity) was used as one of the primary outcomes to objectively examine patients’ level of arousal during the intravitreal injection procedure.
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\nThis study employed multiple linear regression models to explain the predictor variables associated with pain at 1-2 hours and 24 hours post-treatment for VAS and MPQ (main component of SF-MPQ). The optimum multiple regression model identified significant predictor variables, the injection SCR (Skin Conductance Response) amplitude, baseline state anxiety, type of anti-VEGF (aflibercept) and bilateral injections, explained 38% of the variance in VAS scores. The injection SCR amplitude was the most significant predictor of pain at both 1-2 hours and 24 hours post-treatment. Also, questionnaire data reported that at 24 hours post-treatment, 4.7% of participants continued to experience severe sharp, aching or tender pain, and 15.6% reported feeling a moderate tiring-exhausting pain.
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\nA qualitative study exploring the impact of COVID-19 on patient experience was undertaken involving semi-structured telephone interviews (n=17 individuals with neovascular AMD). Nearly half of the participants reported perceived vision deterioration, with some losing their ability to drive. Most participants felt anxious of losing their eyesight due to lack of timely care and absence of communication with the practice. Isolation and fear of losing eyesight impacted participants’ wellbeing with some reporting feeling lonely and depressed. Integrating these findings with individual perspectives captured a comprehensive understanding of the emotional and physical qualities of pain. Adherence to treatment was a key priority for patients over pain and COVID-19 health risks.
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\nAn understanding of pain during and following intravitreal injections may inform clinical practice on implementing pain assessment tools, providing consistent verbal instructions to patients on avoiding contact with the injected eye and advising them on specific pain relief techniques, including topical ice application to self-manage their pain at home. High injection SCR amplitudes and baseline state anxiety may also inform clinical practice on assessing patients’ anxiety at regulated intervals and advising on nurturing self-talk and relaxation techniques to manage their apprehension. Engaging communications to reassure and strengthen patient confidence in their treatment course are meaningful and valuable qualities to patients receiving intravitreal injections.

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