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ORIGINAL ARTICLE
Year : 2019  |  Volume : 26  |  Issue : 2  |  Page : 55-59  

Assessment of patient pain experience during intravitreal ranibizumab and aflibercept injection


1 Department of Ophthalmology, School of Medicine, Bahcesehir University, Istanbul, Turkey
2 Department of Ophthalmology, School of Medicine, Adiyaman University, Adiyaman, Turkey

Date of Web Publication26-Aug-2019

Correspondence Address:
Dr. Burak Bilgin
Department of Ophthalmology, School of Medicine, Bahcesehir University, Istanbul
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/meajo.MEAJO_90_19

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   Abstract 


PURPOSE: The aim of this study was to compare the pain scores of the patients during intravitreal injection of ranibizumab and aflibercept based on patient feedback.
MATERIALS AND METHODS: Seventy-two eyes of 72 patients, who had not previously undergone any intravitreal injection procedures, were included in this study. Thirty-eight patients received ranibizumab, and 34 patients received aflibercept injections. The pain was measured by visual analog scale (VAS). Patients were asked to rate their pain experienced during the injection between 0 (no pain) and 10 (worst pain ever felt) on VAS just after the injection.
RESULTS: VAS pain scores in ranibizumab and aflibercept groups were 3.28 ± 2.45 and 4.20 ± 2.30, respectively. There was a significant difference in average VAS pain scores between groups (P = 0.04).
CONCLUSION: VAS pain scores in aflibercept group were found to be significantly higher than the scores in the ranibizumab group.

Keywords: Aflibercept, intravitreal injection, pain, ranibizumab, visual analog scale


How to cite this article:
Bilgin B, Bilak &. Assessment of patient pain experience during intravitreal ranibizumab and aflibercept injection. Middle East Afr J Ophthalmol 2019;26:55-9

How to cite this URL:
Bilgin B, Bilak &. Assessment of patient pain experience during intravitreal ranibizumab and aflibercept injection. Middle East Afr J Ophthalmol [serial online] 2019 [cited 2019 Sep 16];26:55-9. Available from: http://www.meajo.org/text.asp?2019/26/2/55/265375




   Introduction Top


Intravitreal injection procedures for vitreoretinal disorders are getting more popular and common nowadays. Various pharmacological agents, including antibiotics, antiviral, antifungal, and steroidal drugs, have been injected into the vitreous humor for many years.[1] After the introduction of antivascular endothelial growth factors (VEGF), intravitreal injections gained more acceptance and widespread use among retinal specialists.[2] The efficacy and safety of anti-VEGF agents in the management of neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vascular occlusions (RVOs) were shown in many large-scale, prospective, randomized, controlled multicenter studies regarding intravitreal injection of these agents.[3],[4],[5],[6]

With the increased number of injected patients and increased number of injections per patient, patient comfort and pain experienced during injection became more debatable. Minimizing the pain associated with the procedure is critical for patient compliance to the treatment. Furthermore, pain experienced during injection time can lead to sudden eye and head movements, which may cause some complications.[7] There are various studies discussing the pain experienced during injection of different intravitreal agents, various injection techniques, different anesthetic methods, and needle sizes.[8],[9],[10]

Ranibizumab and aflibercept are the current anti-VEGF agents approved to be delivered through intravitreal injections for the treatment of nAMD, DME, and RVO.[11],[12],[13] Although there are many studies comparing the efficacy and safety of these two approved treatments,[5],[14],[15] there is no study comparing them in terms of pain experienced during injection in the literature. The aim of this study was to compare pain scores of the patients during intravitreal injection of ranibizumab and aflibercept based on patient feedback.


   Materials and Methods Top


This prospective, interventional, nonrandomized, comparative study was carried out at a university education and research hospital, department of ophthalmology between May and December 2017. The study was performed in accordance with the Declaration of Helsinki. Informed consent was obtained from all the patients. Ethical approval was given by the Local Ethics Committee (Approval number: 2017/2-11). All patients were older than 18 years old and were referred to the injection by retina specialists.

Seventy-two eyes of 72 patients, who had not previously undergone any intravitreal injection procedures, were included in this study. Indications for intravitreal injection included nAMD, DME, central RVO, and branch RVO. The diagnoses of the patients in the study group are shown in [Table 1]. Exclusion criteria were a history of previous eye surgery other than cataract extraction, intravitreal injection of any drugs, glaucoma, iridocyclitis, herpetic or nonherpetic keratitis, bullous keratopathy, active conjunctivitis, and having spherical refractive errors >±1 diopters. Patients with poor cooperation and using systemic analgesics or sedative medications were also excluded from the study.
Table 1: The diagnoses of the patients in the study group

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Thiry-eight patients received ranibizumab and 34 patients received aflibercept injections. Before the injection procedure, topical anesthetic 0.5% proparacaine (Alcaine, Alcon-Couvreur, Puurs, and Belgium) drop and 5% povidone-iodine solution were instilled into the eye. All intravitreal injections were performed in the supine position. The periocular region was cleaned with 10% povidone-iodine solution. The eyelids were stabilized by an eyelid speculum. Injections were performed 2 min after the instillation of proparacaine drop. A 30G needle syringe was used to inject the drug into the vitreous cavity through the pars plana at the superotemporal quadrant, 3.5 mm posterior to the limbus. A mild pressure was applied with a sterile cotton stick over the injection site to reduce vitreal reflux and subconjunctival hemorrhage. Same needle size was used for ranibizumab and aflibercept injections. All patients received a drop of antibiotic after the intravitreal injection. All injections were performed by the same physician using the uniform technique for all patients.

The pain was measured by visual analog scale (VAS), which is a response scale for subjective characteristics that cannot be directly measured. VAS has been used to evaluate pain and other symptoms in many studies including ophthalmological studies and shown to be valid and reliable.[16],[17],[18] Patients were asked to rate their pain experienced during the injection between 0 (no pain) and 10 (worst pain ever felt) on VAS just after the injection [Figure 1]. The average of these scores was used for statistical analysis.
Figure 1: Patients were asked to grade their pain felt during the intravitreal injection between 0 and 10 points

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Mann–Whitney U-test was used to compare VAS values and ages between two groups. Sexes were compared with the Chi-square test. P < 0.05 was considered as statistically significant.


   Results Top


The diagnoses of the patients in the study are summarized in [Table 1]. The mean age was 63.94 ± 8.96 in ranibizumab group and 63.11 ± 13.17 in aflibercept group. The mean age of groups were similar (P = 0.79). In ranibizumab group, 22 patients were male and 16 were female. In aflibercept group, 19 patients were male, and 15 were female. Sex between groups was similar (P = 0.86). VAS pain scores in ranibizumab and aflibercept groups were 3.28 ± 2.45 and 4.20 ± 2.30, respectively. There was a significant difference in average VAS pain scores between groups (P = 0.04).

Patients were compared according to the sex. In ranibizumab group, male (22) and female (16) groups were compared. VAS pain scores in male and female groups were 2.40 ± 1.79 and 4.50 ± 2.78, respectively. There was a significant difference in average VAS pain scores between male and female patients in the ranibizumab group (P = 0.002). In aflibercept group, male (19) and female (15) groups were compared. VAS pain scores in male and female groups were 3.42 ± 1.74 and 5.20 ± 2.59, respectively. There was a significant difference for average VAS pain scores between male and female patients in the aflibercept group (P = 0.03). All male (41) and female (31) patients in the study were compared. VAS pain scores in male and female patients were 2.87 ± 1.81 and 4.83 ± 2.67, respectively. There was a significant difference for average VAS pain scores between groups (P = 0.001). Comparison of VAS pain scores is shown in [Table 2].
Table 2: Comparison of visual analog scale pain scores

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   Discussion Top


With the widespread introduction of intravitreal injections, the delivery of the therapeutic agents required for the treatment of many posterior segment diseases to the relevant tissues has been ensured. Most of the patients may require multiple injections. The pain felt during intravitreal injection directly affects the care of the patient as well as the management of the disease. It is necessary for the treatment success to consider the pain caused by the intraocular therapeutic agent as much as the effect on the current clinical situation.

Although there are many studies comparing the efficacy and safety of ranibizumab and aflibercept treatments,[5],[14],[15] this is the first study comparing them in terms of pain experienced during injection in the literature. Since pain is a subjective concept influenced by many factors, it has been difficult to assess its severity. VAS depends on the self-report of the patient, which is the most reliable method to assess the pain. In our study, we have used the VAS which is a widely used method of assessing pain. It has been preferred in many ophthalmologic types of research because of its easy and quick use.[19],[20],[21],[22]

In our study, we have found that VAS pain scores in aflibercept group were significantly higher than the scores in the ranibizumab group. Previous studies regarding pain during intravitreal injections were designed to compare anesthetic protocols, injection site, and needle size.[8],[9],[23] To achieve standardization, all injections in the study were performed in the superotemporal quadrant with the same needle size. When we discuss the reasons for differences in VAS scores in the ranibizumab and aflibercept groups, there may be some factors affecting the pain felt. There are some studies reporting that a sudden rise in intraocular pressure (IOP) after the intravitreal injection is a factor affecting the pain felt by the patient.[24],[25] However, IOP rise after the intravitreal injection is related to the injected volume. In our study, such an effect is not expected since both agents were injected into the eye in equal volume.

The difference between VAS pain scores of the groups may be related to different pH values and components of the drug solutions. Anti-VEGF agents have different chemical formulations. PH values of ranibizumab and aflibercept are 5.32 and 6.05, respectively. However, studies have shown that this pH difference is easily buffered by the vitreous after intravitreal injection.[26] Furthermore, the retina has no nociceptor and sensory innervation to feel the pain related to pH changes.[27] The pain felt during injection is thought to be felt through scleral sensory nerves. When evaluated in this respect, drug reflux that develops after injection should be considered. In our study, a mild pressure was applied with a sterile cotton stick over the injection site to reduce vitreal reflux, and same needle size was used for ranibizumab and aflibercept injections. However, some of the drug injected into the vitreous may have leaked into the subconjunctival area and causes pain at different intensities depending on different pH characteristics of the drugs.

Another thing that we found in our study was the distinction of pain between male and female patients. In both ranibizumab group and the aflibercept group, and in all patients, VAS scores were higher in women. In the literature, many studies conducted with various intravitreal agents reported different results. In the majority of studies, it was reported that there was no relationship between gender and pain felt during intravitreal injection.[10],[28],[29] In their study, Rifkin and Schaal reported that female sex had less pain compared to male sex during intravitreal injection.[30] In accordance with our study, Haas et al. demonstrated that female sex was associated with higher pain score during the intravitreal injection.[9] Pain sensitivity may vary according to psychological and sociocultural status. Some laboratory studies have shown that women have higher pain sensitivity than men. This may be explained by the influence of sex hormones on pain sensitivity. It has been reported that pain threshold and tolerance varies with the stage of the menstrual cycle. Imaging studies of the brain have shown different responses to pain in men and women.[9]

A limitation of our study arises from the subjective assessment method of pain sensation. The main cause of the subjective pain scoring is that the pain felt by the patient is variable and cannot be directly measured. In our study, since there is not any quantitative method to assess the amount of pain felt, we have used the VAS which is a widely used method of assessing pain and preferred in many ophthalmologic types of research.


   Conclusion Top


This is the first study comparing two anti-VEGF agents as ranibizumab and aflibercept in terms of pain felt during the intravitreal injection. Further studies with larger series are needed to confirm the difference of VAS pain scores between these two agents.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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