| Moisseiev et al.77 Moisseiev E, Regenbogen M, Rabinovitch T, Barak A, Loewenstein A, Goldstein M. Evaluation of pain during intravitreal Ozurdex injections vs intravitreal bevacizumab injections. Eye. 2014;28(8):980-5.
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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.88 Güler M, Bilgin B, Çapkin M, Ali Simsek, Bilak S. Assessment of patient pain experience during intravitreal 27-gauge bevacizumab and 30-gauge ranibizumab injection. Korean J Ophthalmol. 2015;29(3):190-4.
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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.99 Haas P, Falkner-Radler C, Wimpissinger B, Malina M, Binder S. Needle size in intravitreal injections - Pain evaluation of a randomized clinical trial. Acta Ophthalmol. 2016;94(2):198-202.
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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. |
| Alattas1010 Alattas K. Patients' tolerance of bimanual lid retraction versus a metal speculum for intravitreal injections. Clin Ophthalmol. 2016;10:1719-21.
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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.1111 Loureiro M, Matos R, Sepulveda P, Meira D. Intravitreal injections of bevacizumab: the impact of needle size in intraocular pressure and pain. J Curr Glaucoma Pract. 2017;11(2):38-41.
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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 Kim1212 Shin SH, Park SP, Kim YK. Factors associated with pain following intravitreal injections. Korean J Ophthalmol. 2018;32(3):196-203.
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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 Burak1313 Bilgin B, Bilak S. Assessment of patient pain experience during intravitreal ranibizumab and aflibercept injection. Middle East Afr J Ophthalmol. 2019;26(2):55-9.
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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.1414 Karimi S, Mosavi SA, Jadidi K, Nikkhah H, Kheiri B. Which quadrant is less painful for intravitreal injection? A prospective study. Eye (Lond). 2019;33(2):304-12.
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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.1515 Khaqan HA, Imtiaz U, Malik IQ, Qureshi BZ, Rehman A. Customized disposable kit versus a conventional stainless steel instrument for an intravitreal injection: a comparison. J Pak Med Assoc. 2020;70(5):909-12.
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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.1616 Soh YQ, Chiam NPY, Tsai ASH, Cheung GCM, Wong TY, Yeo IYS, et al. Intravitreal injection with a conjunctival injection device: a single-center experience. Transl Vis Sci Technol. 2020;9(8):28.
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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.1717 Blyth M, Innes W, Mohsin-Shaikh N, Talks J. A comparison of conventional intravitreal injection method vs InVitria intravitreal injection method. Clin Ophthalmol. 2020;14:2507-13.
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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.1818 Raevis JJ, Karl MD, Parendo AM, Astafurov K, Dugue AG, Agemy AS, et al. Eyelid retraction discomfort with cotton-tipped applicator, unimanual and speculum intravitreal injection techniques: Eyelid retraction technique randomized comparison trial (Eyelid RETRACT). Indian J Ophthalmol. 2020;68(8):1593-5
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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.1919 Örnek N, Apan A, Örnek K, Günay F. Anesthetic effectiveness of topical levobupivacaine 0.75% versus topical proparacaine 0.5% for intravitreal injections. Saudi J Anaesth. 2014;8(2):198-201.
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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 Carvalho2020 Andrade GC, Carvalho AC. Comparison of 3 different anesthetic approaches for intravitreal injections: a prospective randomized trial. Arq Bras Oftalmol. 2015;78(1):27-31.
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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.2222 Chan JC, Chan LP, Yeung CP, Tang W, O YM, Lam WC. Effect of music on patient experience during intravitreal injection. J Ophthalmol. 2020;2020:9120235.
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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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