Pain management during intravitreal injection: integrative review

Santos, Katherine Olga Correia Alves; Dias, Emilly Mayara Feitoza; Santos, Moniery da Silva; Ribeiro, Caíque Jordan Nunes; Ribeiro, Maria do Carmo de Oliveira

doi:10.5935/2595-0118.20210039

Brasil

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REVIEW ARTICLE • BrJP 4 (3) • Jul-Sep 2021 • https://doi.org/10.5935/2595-0118.20210039 linkcopy

Pain management during intravitreal injection: integrative review

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

BACKGROUND AND OBJECTIVES: Intravitreal injection is a very common surgical procedure in the treatment of diabetic retinopathy, diabetic macular edema, and retinal vein occlusion. Because it’s a treatment that causes pain and discomfort for the patient, therapies that reduce procedural pain are necessary. The aim of the study was to conduct an integrative review on pain management during administration of intravitreal injection.

CONTENTS: The study was carried out in January 2021 in three databases (Pubmed, Bireme and Scielo) using the descriptors “intravitreal injections”, “pain management” and “analgesia”. After reading and analysis, 15 articles were selected. The results show several factors associated with pain management during intravitreal injection, such as the use of different anesthetics, needle gauge, injected medication, different surgical instruments and use of music.

CONCLUSION: Studies have shown that proparacaine, especially when associated with subconjunctival lidocaine, ranibizumab and alternative techniques for intravitreal injection are preferable approaches to pain management during the procedure.

Keywords: Analgesia; Intravitreal injections; Pain; Pain management

Autores	Country of origin	Design and level of evidence	Sample size	Objective
Moisseiev et al.⁷	Israel	Non-randomized, intervention study 2B	57 patients	Assess the pain associated with Ozurdex IVI and compare it to that associated with bevacizumab IVI.
Güler et al.⁸	Turkey	Non-randomized, intervention study 2B	70 patients	Compare patients' pain scores during IVI with 27-G bevacizumab needles and 30-G ranibizumab needles.
Haas et al.⁹	Austria	Randomized, blind, clinical trial 1B	280 patients	Evaluate the influence of the needle size used for IVI on the patients' experience of pain.
Alattas¹⁰	Saudi Arabia	Prospective observational study 3B	56 patients	Compare patients' acceptance and correlate their pain level for bimanual versus metal speculum fixation in IVI.
Loureiro et al.¹¹	Portugal	Cross-sectional, randomized study 3B	54 eyes	Assess the impact of needle size on intraocular pressure and pain: compare the effect of 30-gauge versus 27-G needle size on patients' intraocular pressure and pain experience after bevacizumab IVI.
Shin, Park and Kim¹²	Korea	Prospective observational study 3B	147 patients	Investigate factors associated with pain intensity after IVI and factors that may be associated with changes in pain intensity in patients who received repeated injections.
Bilgin and Bilak¹³	Turkey	Non-randomized, intervention study. 2B	72 patients	Compare patients' pain scores during ranibizumab and aflibercept IVI based on patient feedback.
Karimi et al.¹⁴	Iran	Randomized clinical trial 1B	1.004 patients	Assess the relation between site of injection and level of pain after bevacizumab IVI.
Khaqan et al.¹⁵	Pakistan	Randomized study 1B	2.250 patients	Compare the level of discomfort caused between a customized disposable kit and a conventional stainless-steel instrument
Soh et al.¹⁶	Singapore	Randomized, prospective study 1B	140 patients	Evaluate the clinical performance of the assistant device of IVI (InVitria) compared to the conventional free hand technique.
Blyth et al.¹⁷	England	Prospective observational study 3B	58 patients	Compare the use of the conventional IVI method with the InVitria device.
Raevis et al.18	United States	Randomized, open clinical trial 1B	99 patients	Test discomfort experienced during IVI with eyelid retraction with eyelid speculum, cotton-tipped applicator (CTA) and unimanual eyelid retraction techniques.
Örnek et al.¹⁹	Turkey	Randomized, prospective study 1B	96 patients	Compare the anesthetic efficacy of topical levobupivacaine 0.75% and proparacaine 0.5% in patients undergoing IVI.
Andrade and Carvalho²⁰	Brazil	Randomized, prospective study 1B	92 patients	Compare the anesthetic efficacy of topical proparacaine drops, subconjunctival lidocaine and lidocaine gel 2%.
Chan et al.²²	Hong Kong	Randomized, parallel, controlled clinical trial 1B	76 patients	Assess the effect of music during IVI.

Authors	Results
Moisseiev et al.⁷	During the IVI, there were no significant differences between the scores of pains when Ozurdex and bevacizumab were used. The score of pain was higher in pseudophakic eyes (VAS=32.23 ± 23.0; p=0.005) when compared to phacic eye (VAS=15.6 ± 16.8).
Güler et al.⁸	Ranibizumab showed less influence on pain (VAS=1.06 ± 0.91) compared to bevacizumab (VAS=1.94 ± 1.55; p=0.005). Women experienced more pain with bevacizumab injection (VAS=2.35 ± 1.77) than with ranibizumab injection (VAS=1.16 ± 1.01; p=0.016).
Haas et al.⁹	No association between needle gauge and pain intensity was found, and the suggested approach is according to the patient's need. Pain perception was more significant in older patients and women.
Alattas¹⁰	The use of bimanual fixation provided the patient with more comfort and less pain (0.53 ± 0.62) than the use of metal fixation (1.91 ± 1.14; p=0.003).
Loureiro et al.¹¹	There was no significant difference in pain scores between the 27-gauge (VAS=3.0 ± 2.5) and 30-gauge (VAS=3.2 ± 2.6; p=0.003) needles.
Shin, Park and Kim¹²	Women (VAS=3.1 ± 1.5) were more susceptible to pain than men (VAS=2.4 ± 1.2; p=0.003). The anterior chamber paracentesis procedure reduced pain during the procedure, as well as the anti-VEGF IVI showed lower pain scores. Patients who received repeated injections noted pain perception less or similar to previous procedures.
Bilgin e Burak¹³	Application of ranibizumab (VAS=3.28 ± 2.45; p=0.04) showed lower pain intensity than aflibercept (VAS=4.20 ± 2.30). Women in both groups experienced more pain (VAS=4.83 ± 2.67; p=0.001) during the procedure than men (2.87 ± 1.81). Additionally, pain among women was even higher with aflibercept injection (VAS=5.20 ± 2.59).
Karimi et al.¹⁴	The following pain scores were observed according to the quadrants of application: superior nasal (1.5 ± 1.7), inferior nasal (3.0 ± 2.3), superior temporal (4.0 ± 2.0) and inferior temporal (3.0 ± 2.1). A statistically significant correlation was found between patient sex and pain score (p<0.001).
Khaqan et al.¹⁵	The use of the disposable kit is more beneficial for painless tissue handling, as well as being faster and less costly. Of 1.500 eyes submitted to the use of the kit, no pain was reported by patients in 1.231 eyes (82.06%), while with the conventional method no pain was perceived in 1.014 of the 1.200 analyzed eyes (84.5%).
Soh et al.¹⁶	The pain scores did not present significant differences, and in the conventional technique of IVI the VAS was equal to 2.03 ± 1.73, while in the InVitria technique, the VAS was 2.13 ± 2.20. However, it was found that the new technique has a shorter execution time than the conventional one.
Blyth et al.¹⁷	When applying the questionnaire, the data collected showed an improvement in pain scores in each phase of the procedure in cases where InVitria was used compared to the conventional method; as for the time spent in application, InVitria was, on average, 1 minute and 32 seconds faster than the conventional method.
Raevis et al.¹⁸	The palpebral retraction was less painful with the unimanual and CTA techniques, providing more comfort to the patient. Pain scores for eyelid retraction: unimanual group (0.778 ± 0.70); CTA group (0.945 ± 1.28); speculum group (1.561 ± 1.28) significant difference between groups (p=0.006).
Pharmacological management of IVI-related pain
Örnek et al.¹⁹	Anesthesia with proparacaine (VAS=34.18 ± 14.83) is more effective in relieving pain during IVI than levobupivacaine (VAS=44.77 ± 16.42; p=0.003).
Andrade and Carvalho²⁰	Subconjunctival lidocaine 1% associated with proparacaine is more effective in reducing pain scores than proparacaine 0.5% and lidocaine gel 2%.
Non-pharmacological management of IVI-related pain
Chan et al.²²	There were no significant differences between the pain scores of the music therapy and control groups (VAS=31.92 ± 28.30 vs. 34.95 ± 30.49, respectively, p=0.655). Nevertheless, patients in the experimental group reported less anxiety, and also preferred the use of music in upcoming procedures.

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[TFN1] VAS=visual analog scale.