Why carry out the study? | |
Studies find that patients report a certain degree of fear and anxiety regarding intravitreal injection, and concerns related to pain from intravitreal injections are one of the key factors mentioned by patients when asked about therapy. | |
We systematically review comparative studies on the needle gauge size used for intravitreal anti-vascular endothelial growth factor injection therapy and the pain experience reported by the patients. | |
What was learned from the study? | |
Our network meta-analysis found a clear relationship between thinner needle gauge sizes and lower pain experience from intravitreal injections. | |
However, pain is a complex experience, and studies report many influencing aspects related to intravitreal injections. Nevertheless, we recommend using the thinnest feasible gauge size when delivering intravitreal injection therapy. |
Introduction
Methods
Study Design
Study Eligibility Criteria and Outcome of Interest
Population
Intervention and Comparison
Outcomes
Study Type
Information Source, Search Strategy, and Study Selection
Data Items, Data Collection, and Risk of Bias within Studies
Data Synthesis and Risk of Bias across Studies
Results
Study Selection
Characteristics of the Eligible Studies
Reference | Country | Design | Participant eligibility | Details of the anti-VEGF treatment | Pain measurement |
---|---|---|---|---|---|
Aderman et al. (2018) | USA | Prospective single-center RCT | Patients with AMD, diabetic macular edema, or retinal vein occlusion receiving bilateral anti-VEGF treatment were recruited to participate in this study | - Eye was cleaned with povidone-iodine - Proparacaine was instilled twice approximately 15 s apart - No eye speculum, eyelids were kept apart bimanually, and povidone-iodine was instilled - Intravitreal ranibizumab (0.5 mg/0.05 mL) or aflibercept (2 mg/0.05 mL) was administered 4 mm from the limbus in the inferotemporal quadrant - Injections were performed by physicians - All patients had one eye treated with a 30-gauge needle and the other eye treated with a 33-gauge needle. Allocation of the left or right eye to the needle groups was randomized | Pain was measured with the Numeric Pain Rating Scale, which is a segmented numeric version of the VAS. Pain was measured before and immediately after the injection |
Alshahrani et al. (2021) | Saudi Arabia | Prospective single-center RCT | Patients with macular edema due to diabetic retinopathy, exudative AMD, or retinal vasculopathy. Patients were treatment-naïve and the anti-VEGF injection in the study was their first injection. Patients were not included if they had previously experienced a painful ocular condition | - Eye was cleaned with povidone-iodine - Xylocaine gel was instilled; after 10 min, an eye speculum was inserted, and povidone-iodine was instilled - Intravitreal ranibizumab (0.5 mg/0.05 mL) was administered 3.5 mm from the limbus in the inferotemporal quadrant - Injections were performed by retina specialists - Patients were randomized to either 30-gauge or 32-gauge needles | Pain was measured with a VAS from 1 to 10. Pain was measured immediately after the intravitreal injection |
Eaton et al. (2013) | USA | Prospective single-center RCT | Patients receiving bilateral anti-VEGF treatment were recruited to participate in this study | - Eye was cleaned with povidone-iodine - Anesthesia was performed with one of three topical methods: subconjunctival lidocaine 2% with epinephrine (81% of participants), topical lidocaine gel 2% (3% of participants), or topical tetracaine 0.5% (16% of participants) - An eye speculum was inserted, and povidone-iodine was instilled again - Intravitreal ranibizumab (0.5 mg/0.05 mL) or aflibercept (2 mg/0.05 mL) was administered - Injections were performed by physicians using methods with which they were most comfortable - All patients had one eye treated with a 30-gauge needle, and the other eye treated with a 33-gauge needle. Allocation of the left or right eye to the needle groups was randomized | Pain was measured on a 5-point Likert scale during the injection, immediately after the intravitreal injection, later that day, and the next day |
Güler et al. (2015) | Turkey | Prospective single-center non-randomized comparative trial | Patients were treatment-naïve and the anti-VEGF injection in the study was their first injection. Patients were excluded if previous eye surgery other than for cataract, or a history of herpetic eye disease, glaucoma, uveitis, or active conjunctivitis, keratitis, bullous keratopathy, or use of systemic analgesics or sedatives | - Eye was cleaned with povidone-iodine - Proparacaine 0.5% was instilled, eye speculum was inserted, povidone-iodine was instilled, and proparacaine 0.5% was instilled again - Intravitreal bevacizumab or ranibizumab was administered 3.5–4.0 mm from the limbus in the inferotemporal quadrant - Patients were allocated to either 27-gauge bevacizumab (1.25 mg/0.05 mL) or 30-gauge ranibizumab (0.5 mg/0.05 mL) | Pain was measured on a VAS from 0 to 10. Pain was measured immediately after the intravitreal injection |
Haas et al. (2016) | Austria | Prospective single-center RCT | Patients receiving intravitreal injection therapy, ability to report pain perception, and no history of ocular pain related to intravitreal injections, active ocular infection or inflammation, known trigeminal neuralgia, or allergy to drugs involved | - Eye was cleaned with povidone-iodine - Tetracaine 0.5% was instilled, eye speculum was inserted - Intravitreal bevacizumab (2.5 mg/0.10 mL) was administered 3.5 mm or 4.0 mm from the limbus for pseudophakic or phakic eyes, respectively - Patients were randomized to either 27-gauge or 30-gauge needle | Pain was measured on a VAS from 0 to 10 and on the Wong-Baker FACES scale from 0 to 10. Pain was measured immediately after the intravitreal injection |
Lourerio et al. (2017) | Portugal | Prospective single-center RCT | Patients were treatment-naïve and the anti-VEGF injection in the study was their first injection. Patients were excluded if any history of eye surgery other than for cataract, use of IOP-lowering drugs, corneal diseases, or complaints of ocular pain prior to the procedure | - Eye was cleaned with povidone-iodine - Oxybuprocaine 0.4% was instilled, povidone-iodine was instilled, and eye speculum was inserted - Intravitreal bevacizumab (1.5 mg/0.05 mL) was administered 3.5–4.0 mm from the limbus in the superotemporal quadrant - Patients were randomized to either 27-gauge or 30-gauge needle | Pain was measured with a VAS from 0 to 10. Pain was measured immediately after the intravitreal injection |
Rodrigues et al. (2011) | Brazil | Prospective multi-center non-randomized comparative trial | Patients eligible for anti-VEGF therapy with any of the following diseases: AMD, diabetic retinopathy or maculopathy, retinal vein occlusion, inflammatory macular edema, choroidal neovascularization, polypoidal choroidal vasculopathy, central serous chorioretinopathy | - Eye was cleaned with povidone-iodine - Moxifloxacin was instilled - Tetracaine 0.5% was instilled three times - Eye speculum was inserted - Intravitreal bevacizumab (1.5 mg/0.05 mL) was administered 3.5 mm from the limbus in the superotemporal quadrant - Patients were allocated to 26-gauge, 27-gauge, 29-gauge, or 30-gauge needle | Pain was measured with a numeric scale ranging from 0 to 10. Pain was measured immediately after the intravitreal injection |
Sasajima et al. (2018) | Japan | Prospective single-center RCT | Patients eligible for anti-VEGF therapy | - Eye was cleaned with povidone-iodine - Lidocaine 2% was instilled - Eye speculum was inserted - Intravitreal ranibizumab (0.5 mg/0.05 mL) or aflibercept (2 mg/0.05 mL) was administered 3.5–4.0 mm from the limbus in the superonasal or superotemporal quadrant - Injections were performed by surgeons - Patients were randomized to either 30-gauge or 34-gauge needle | Pain was measured with a numeric scale ranging from 0 to 10. Pain was measured immediately after the intravitreal injection |
Van Asten et al. (2015) | Netherlands | Prospective single-center RCT | Patients with AMD, diabetic macular edema, or retinal vein occlusion eligible for at least two consecutive anti-VEGF injections within 6 weeks | - Eye was cleaned with povidone-iodine - Oxybuprocaine and tetracaine 1% was instilled. Further, an additional two rounds of povidone-iodine and tetracaine 1% were instilled - Eye speculum was inserted - Intravitreal bevacizumab was administered 3.5 mm or 4.0 mm from the limbus for pseudophakic or phakic eyes, respectively - Injections were performed by a surgeon - Randomization allocated the sequence of treatment, i.e., first the eye was treated using either the 30-gauge or 33-gauge needle according to the randomization, and the other gauge size was used at the next visit | Pain was measured with a numeric scale ranging from 0 to 10. Pain was measured immediately after the intravitreal injection |
Reference | Study groups | Age, years | Females, % | Anti-VEGF drug used, % | Numbers allocated (eyes/patients) | Numbers analyzed (eyes/patients) |
---|---|---|---|---|---|---|
Aderman et al. (2018) | 30-gauge needle | – | – | – | 49/49a | 49/49a |
33-gauge needle | – | – | – | 49/49a | 49/49a | |
Alshahrani et al. (2021) | 30-gauge needle | 78 ± 11 | 42% | RNZ 100% | 86/86 | 86/86 |
32-gauge needle | 78 ± 11 | 40% | RNZ 100% | 86/86 | 86/86 | |
Eaton et al. (2013) | 30-gauge needle | – | – | – | 70/70a | 70/70a |
33-gauge needle | – | – | – | 70/70a | 70/70a | |
Güler et al. (2015) | 27-gauge needle | 65 ± 10 | 49% | BVZ 100% | 35/35 | 35/35 |
30-gauge needle | 60 ± 12 | 54% | RNZ 100% | 35/35 | 35/35 | |
Haas et al. (2016) | 27-gauge needle | 72 ± 11 | 55% | BVZ 100% | 104/104 | 104/104 |
30-gauge needle | 75 ± 11 | 52% | BVZ 100% | 104/104 | 104/104 | |
Lourerio et al. (2017) | 27-gauge needle | 70 ± 10 | – | BVZ 100% | 27/24 | 27/24 |
30-gauge needle | 69 ± 10 | – | BVZ 100% | 27/24 | 27/24 | |
Rodrigues et al. (2011) | 26-gauge needle | 70 ± 13b | 59%b | BVZ 100% | 16/16 | 16/16 |
27-gauge needle | BVZ 100% | 23/23 | 23/23 | |||
29-gauge needle | BVZ 100% | 83/83 | 83/83 | |||
30-gauge needle | BVZ 100% | 83/83 | 83/83 | |||
Sasajima et al. (2018) | 30-gauge needle | 75 ± 13 | 35% | AFL 80% RNZ 20% | 69/c | 69/c |
34-gauge needle | 76 ± 8 | 30% | AFL 86% RNZ 14% | 71/c | 71/c | |
Van Asten et al. (2015) | 30-gauge needle | 68 ± 13 | 36% | BVZ 100% | 36/36d | 36/36d |
33-gauge needle | 68 ± 13 | 36% | BVZ 100% | 36/36d | 36/36d |
Results of Individual Studies
Risk of Bias within Studies
Network Meta-Analyses
-
27-gauge needle (d: −0.4; 95% CI −1.9 to 1.2; P = 0.66)
-
29-gauge needle (d: −2.7; 95% CI −3.2 to −2.3; P < 0.00001)
-
30-gauge needle (d: −3.8; 95% CI −5.3 to −2.4; P < 0.00001)
-
32-gauge needle (d: −4.3; 95% CI −5.2 to −3.5; P < 0.00001)
-
33-gauge needle (d: −4.5; 95% CI −5.4 to −3.7; P < 0.00001)
-
34-gauge needle (d: −5.3; 95% CI −6.2 to −4.4; P < 0.00001)