Oral Presentation at EuRetina Annual Congress 2020

Can use of an intravitreal injection guide improve procedure efficiency compared to standard technique of injection delivery?

ABSTRACT

BACKGROUND:

Various intravitreal injection devices are available commercially. Data has been published previously on safety profiles and patient comfort, but none to date on their effect on procedure efficiency and patient pathway. This study is a time and motion analysis on the use of an injection guide by an experienced ophthalmic nurse practitioner.

METHODS:

In this prospective single-centre study, 43 consecutive patients received an intravitreal injection first by standard injection technique, with next injection delivered using an Intravitreal Injection Guide. All injections were performed by same experienced ophthalmic nurse practitioner. Primary outcomes were total patient time in procedure room and total procedure time. Data was also collected on complication rates, medication used, laterality and patient demographics.

RESULTS:

Use of the injection guide showed a statistically significant decrease in mean total time in procedure room of 41.7 seconds (P < 0.001, 95% CI 19.7;63.8), and in mean procedure time of 55.9 seconds (P < 0.001, 95% CI 45.3;66.2). The median total time spent in the procedure room and procedure time were lower with pre-filled Lucentis (Ranibizumab) compared to Eylea (Aflibercept) (P < 0.05). No complications were reported.

CONCLUSION:

Use of an intravitreal injection guide can provide a cost-neutral and safe method of enhancing efficiency on an ophthalmic nurse practitioner led list, with a safety profile similar to standard technique.

ARTICLE

INTRODUCTION:

The use of intravitreal injections in treatment of a wide variety of retinal conditions such as neovascular age-related macular degeneration (nAMD), diabetic retinopathy and vein occlusions is well established,[1-3]. Millions of injections are delivered worldwide per annum and on a background of an expanding elderly population, their use is set to increase exponentially over the next decade,[4]. In the United Kingdom alone, the Royal College of Ophthalmologists has predicted an increase in nAMD cases of 53 percent between 2015 to 2035,[5]. To cater for this growing demand, nurse practitioners, hospital optometrists and orthoptists are increasingly training to deliver injections,[6]. From a patient perspective, provision of therapy has vastly improved visual outcomes,[7], but at the expense of undergoing invasive treatment once a month or bi-monthly for many years.

Various teams globally have developed innovative intravitreal injection devices,[8-11]. Published evidence has shown improvement in pain scores, enhanced operator preference and patient satisfaction. However, to date there has been no published data from a time and motion study to ascertain improvement in procedure efficiency. We present results from a locally developed intravitreal injection guide to assist in developing such evidence.

MATERIALS AND METHODS:

The study was performed between November 2019 and February 2020 at the Royal Eye Infirmary, Plymouth, U.K. A single experienced advanced nurse practitioner (AT) performed all injections (experience of 8000 injections with standard technique and 1000 with Waqar-Malosa Intravitreal Injection Guide). As injection delivery by either standard technique or injection guide are both considered standard of care in our department (dependent on operator or patient preference), ethics approval was not required. Local Clinical Effectiveness Group approval for use of the guide was obtained, and it is also both CE marked and FDA approved (510 (k) Exempt).  All patients were seen by the medical retina team and informed decision on treatment made with consent form completed as per routine. The study included both treatment naïve and previously treated patients.

43 consecutive patients received an intravitreal injection with the standard technique, followed by injection delivery with the Malosa Intravitreal Injection Guide when next injection clinically indicated.

For both visits, the same assistant called the patient in and asked them to sit on the procedure bed. As soon as the patient entered the room, stopwatch A was started and stopped when they left the room at the end (to record total time spent by patient in procedure room). Whilst the nurse practitioner completed the safety checks with the patient and case notes (confirming name and date of birth, checking and marking which eye to be injected and with which medication, confirming any changes to recent health that may be a contraindication and marking the relevant eye), the AHP placed the injection pack on a trolley. The patient was then asked to lie down on the bed. The nurse opened and set up the injection pack, whilst the AHP instilled 0.5% Proxymetacaine Hydrochloride eye drops followed by 1.5 ml of 5% povidone-iodine solution on patient’s lid margins and into the lower fornix. The AHP then opened, using a non-touch technique, a pre-filled Lucentis injection or helped draw up an Eylea injection into a 1 ml syringe. The nurse practitioner instilled 0.5% proxymetacaine hydrochloride eye drops and cleaned the lids with 5% povidone-iodine, ensuring some entered again into the fornices.

Stop watch B was now started on both visits to document time taken for the injection itself. It was stopped when the patient’s vision was checked (ability to count fingers) at end of the procedure.

For the standard technique (Basic IVT Pack MMK470/1, Malosa Medical), a drape was placed followed by a guarded lid speculum. The patient was asked to look inferonasally and a drop of 0.5% proxymetacaine hydrochloride was instilled in the superotemporal quadrant followed by one drop of 5% povidone-iodine. A calliper was used to indicate site of injection (3.5 mm for pseudophakic and 4 mm for phakic eyes). The injection was delivered (0.05 ml of medication) in the super-temporal quadrant using a 30 gauge needle (two-thirds of needle length entry). A cotton bud was used to check for vitreous wicks and Minims Chloramphenicol 0.5% eye drops instilled on injection site.  The speculum and drape were removed, lids cleaned with normal saline and dried, and vision checked.

For the Intravitreal Injection Guide (Core IVT Pack MMK877, Malosa Medical), the upper lid was hooked with the lash guard and patient asked to look inferonasally. A drop of 0.5% proxymetacaine hydrochloride was instilled in the superotemporal quadrant followed by one drop of 5% povidone-iodine. As per manufacturers recommendations, the triangular footplate was placed on the sclera with the apex at the limbus. The injection (0.05 ml of medication) was delivered through the central chamber (4 mm from limbus with 7 mm needle length entry) using a 30-gauge needle and sustained plunger pressure for 5 seconds to minimise reflux. The guide was removed, a cotton bud used to check for vitreous wicks and Minims Chloramphenicol 0.5% eye drops administered onto injection site. Lids were cleaned with normal saline and dried, and vision checked.

For both visits, the post injection steps were the same. The patient was sat up in the bed and given both verbal instructions and a leaflet on symptoms of complications and point of contact in the department should there be any concern. They were then stood up and escorted out of the room by the assistant. All patients were also given an Outcome Form which they handed in to the reception to allow the administrative team to book their next appointment.

RESULTS:

Statistical analysis was performed using R 3.6.2. Counts and percentages were used to summarize categorical variables. Continuous variables were summarized using mean ± standard deviation (SD) or median and interquartile range (IQR) for normal and non-normal variables, respectively. Wilcoxon rank sum or signed rank test was used to test the null hypothesis of no difference between groups for non-normal data and t-test was for normally distributed variables. The unadjusted average difference and 95% confidence interval were calculated when t-test was used. The difference in time was calculated for each patient. Linear regression used to assess factors associated with the difference in time. Hypothesis testing was performed at 5% level of significance.

The study sample included 43 patients. The average age of the included patients was 76.9 ± 12.8 years (Table 1). Males and females represented 32.6% and 67.4% of the included patients, respectively. The median number of pre-study injections was 11 (IQR 5; 22.5). Indications for treatment included diabetic retinopathy (9.3%), vein occlusions (18.6%) and wet age-related macular degeneration (72.1%). No complications were reported with either technique. The average total time and procedure time were lower with the use of Intravitreal Injection Guide compared to when the standard technique was used.

      [ALL]     
       N=43     
Age76.9 ± 12.8
Gender:               
    F   29 (67.4%)  
    M   14 (32.6%)  
No of pre-study injections11.0 [5.00;22.5]
Laterality:               
    Bilateral   3 (6.98%)   
    Left   26 (60.5%)  
    Right   14 (32.6%)  
Indications for treatment:               
    Diabetic Retinopathy (DR)   4 (9.30%)   
    Vein Occlusions (VO)   8 (18.6%)   
   Wet Age-Related Macular Degeneration (wAMD)   31 (72.1%)  
Drug:               
    Eylea   13 (30.2%)  
    Bilateral Eylea   3 (6.98%)   
    Lucentis   26 (60.5%)  
    Bilateral Lucentis   1 (2.33%)   
Standard technique (Total Time in Procedure Room)373 ± 92.2
Standard technique (Procedure Time)262 ± 88.0
Intravitreal injection guide (Total Time in Procedure Room)    RoomRoom)331 ± 87.0
Intravitreal injection guide (Procedure Time)206 ± 66.3
Continuous data was presented as mean ± SD or median (IQR). Categorical data was presented as count and %. Time is presented as seconds
Table 1

Signed rank test showed that there was a statistically significant difference in total time spent in procedure room (P < 0.001) and procedure time (P < 0.001) between both techniques (Table 2). The median total time in the procedure room was lower when the injection guide was used compared to the standard technique. The median procedure time was also lower with the injection guide. The unadjusted average difference in the total time spent in procedure room was 41.7 seconds while the unadjusted average difference in procedure time was 55.9 seconds.

 Standard techniqueIntravitreal Injection GuideΔ 95% CIP
Total Time in Procedure Room373 ± 92.2331 ± 87.041.7 (19.7; 63.8)< 0.001
Procedure Time262 ± 88.0206 ± 66.355.9 (45.3; 66.2)< 0.001
Data was presented as mean and standard deviation Statistical analysis was performed using unpaired t-test Δ Standard technique – Intravitreal injection guide
Table 2

Overall, the median total time spent in the procedure room and procedure time were lower with Lucentis compared to Eylea (P < 0.05 for all comparisons). Density plots for both primary outcomes showed a left-shit with the injection guide.

Linear regression was also used to assess factors associated with procedure time. Results showed laterality and drug used were significantly associated with the procedure time for both techniques. For the standard technique, the average procedure time was higher by 300 seconds for bilateral injections compared to unilateral left injections (B = 301, P < 0.001). The average time was not different between injections with right and left laterality. The average procedure time was lower by 48 seconds in injections when Lucentis was administered compared to when Eylea was administered (B = -48.41, P = 0.007).

Similar results were observed with the Intravitreal Injection Guide. However, an interesting finding was that the average increase in procedure time was higher by only 200 seconds in bilateral injections compared to unilateral injections (B = 203, P < 0.001). This indicates that the use of the guide saves approximately 100 seconds in bilateral injections.

DISCUSSION:

Provision of intravitreal injections has improved tremendously over the last decade. Many patients have now had dozens of injections over the years, and expectations understandably have heightened. Of all the steps in the procedure, patients mostly find the drape and speculum most uncomfortable,[11,12]. Many physicians do not routinely use a drape, and indeed the recent European Retina Society guidance does not consider a drape necessary,[13]. It is important however to ensure lashes do not touch the needle to prevent endophthalmitis, such as with a guarded lid speculum.

To meet growing demand, allied health professionals are increasingly playing a central role in service provision. Pioneered in the United Kingdom, nurse practitioner led injections have been found to be safe and the concept is gaining traction worldwide,[14-16]. As an expansion of the idea, the Royal College of Ophthalmologists have also supported involvement of suitable trained hospital optometrists and orthoptists in this specialist role. Ensuring high-quality training and standardised completion of procedure are essential to maintain best practice. The current COVID-19 pandemic will cause expanding waiting lists, and maintaining multi-disciplinary teams will be crucial.

Delay in treatment can result in permanent visual damage and is a challenge for most health-care systems,[17]. It is therefore desirable to increase list efficiency, allowing health services to deliver treatment to more patients per annum whilst maintaining patient comfort and procedure safety. Intravitreal Injection Devices have been developed by different teams internationally to help meet this objective. Of varying designs, they allow injection delivery without a drape or speculum and with safety profiles comparable to standard techniques,[8,9,10,18,19].

The Waqar-Malosa Intravitreal Injection Guide consists of a triangular base plate which is curved to follow the contour of the eye and has three studs at the corners for stabilisation of the eye. Its apex has an arrow to indicate placement at the limbus. The base plate is connected to a cylindrical chamber, which in turn is connected to a handle and a lash guard. The lash guard is able to effectively splay the lashes away from the site of the injection and the injection needle (thus obviating the need for a speculum/drape whilst also reducing the risk of infection) and the cylindrical chamber allows 7 mm of a 13 mm/30 gauge needle to enter the eye (thus eliminating the risk of over-insertion). Once the base plate is firmly placed on the surface of the eye, the chamber will only allow the injection to be delivered 4 mm from the limbus, and perpendicular to the sclera, thereby ensuring precise delivery through the pars plana and avoiding lenticular/retinal damage. An incorporated metal swage tube in the chamber prevents intra-ocular plastic particulate entry.

Whilst the various devices positive impacts on pain scores and patient satisfaction are documented, no evidence exists to quantify efficiency gains. Previous studies have made mention of decreased procedure time, however evidence has not been presented to support this thought,[20].

This study demonstrates a statistically significant reduction in both Total Time in Procedure Room and Procedure Time with use of an intravitreal injection guide on an Ophthalmic Nurse Practitioner list. The recent Getting It Right First Time (GIRFT) report has suggested 16 injections as standard in a four hour session for the NHS,[21]. It is estimated that 388 031 intravitreal injections were performed across the NHS in 2015,[22], and currently in our unit 6000 injections are delivered per annum. Based on these figures, use of the guide increases capacity by one injection per list, 375 injections per annum for a unit our size, and 25000 injections per annum for the NHS. GIRFT also highlighted some units perform up to 30 injections per four hour session. In this instance capacity gains will be higher at two injections per list, 750 per annum for a unit our size and 50,000 injections per annum for the NHS. If the cost of an injection guide pack remains similar to a standard pack (this is feasible as the guide replaces material costs for a drape, caliper and speculum), the outcome is a significant cost-neutral increase in delivery capacity for the health service.

In keeping with previously published data, we have found use of pre-filled Lucentis syringes to be more efficient than drawing up an Eylea injection,[23]. Reassuringly, Eylea will also soon be available as a pre-filled formulation.  As more anti-VEGF agents undergo development, our data supports the use of pre-filled syringes not only for safety but also for procedure efficiency. Although the sample size is small, it has been interesting to note reduction in time for bilateral injections with both the guide and pre-filled Lucentis. This can be attributed to ease of set-up of new sterile kit between eyes, but a larger sample size is required to draw more concrete conclusions.

Strength of the study is comparison of both techniques between the same patients to minimise the effect of poor mobility, difficult communication and patient positioning on measured outcomes. In addition, standardisation has been achieved by using the same nurse injector and assistant for all cases, and data has been collected not only for the procedure time, but also total time spent by patient in the procedure room. This methodology provides a more accurate understanding of the true impact of efficiency gains for service delivery planning, as any patient related factors (e.g. poor mobility) that could off-set stand alone gains during the procedure are also considered.

 Areas for further work include comparing similar outcomes between different types of intravitreal injection devices, across injectors of varying experiences and professional backgrounds (i.e. doctors, nurses, orthoptists, optometrists), and to explore the effect of injection devices on learning curves for injectors in training. A larger sample size would also be required for more accurate confidence intervals.

In conclusion, use of an intravitreal injection guide results in a statistically significant reduction in both time spent by patient in the procedure room, and the procedure itself. This can support a cost neutral and exponential increase in service delivery for the NHS, whilst enhancing the patient experience.

REFERENCES:

  1. CATT Research Group, Martin DF, Maguire MG, et al. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med. 2011;364(20):1897‐1908. doi:10.1056/NEJMoa1102673.
  2. Hykin P, Prevost AT, Vasconcelos JC, et al. Clinical Effectiveness of Intravitreal Therapy With Ranibizumab vs Aflibercept vs Bevacizumab for Macular Edema Secondary to Central Retinal Vein Occlusion: A Randomized Clinical Trial [published online ahead of print, 2019 Aug 29]. JAMA Ophthalmol. 2019;137(11):1256‐1264. doi:10.1001/jamaophthalmol.2019.3305
  3. Prünte C, Fajnkuchen F, Mahmood S, et al. Ranibizumab 0.5 mg treat-and-extend regimen for diabetic macular oedema: the RETAIN study. Br J Ophthalmol. 2016;100(6):787‐795. doi:10.1136/bjophthalmol-2015-307249
  4. Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2(2):e106‐e116. doi:10.1016/S2214-109X(13)70145-1
  5. The Way Forward Report: Age related macular degeneration and diabetic retinopathy. The Royal College of Ophthalmologists. 2015.
  6. Ophthalmic Service Guidance – Intravitreal Injection Therapy. The Royal College of Ophthalmologists. August 2018.
  7. Mehta H, Tufail A, Daien V, et al. Real-world outcomes in patients with neovascular age-related macular degeneration treated with intravitreal vascular endothelial growth factor inhibitors. Prog Retin Eye Res. 2018;65:127‐146. doi:10.1016/j.preteyeres.2017.12.002
  8. Ratnarajan G, Nath R, Appaswamy S, et al. Intravitreal injections using a novel conjunctival mould: a comparison with a conventional technique. Br J Ophthalmol. 2013;97(4):395‐397. doi:10.1136/bjophthalmol-2012-302155
  9. Han DP, McKenney KC, Kim JE, et al. CLINICAL EVALUATION OF THE RAPID ACCESS VITREAL INJECTION GUIDE: A Handheld Instrument for Assisting Intravitreal Injections. Retina. 2017;37(4):778‐781. doi:10.1097/IAE.0000000000001229
  10. Watanabe K, Masafumi U, Mohamed Y, et al. Safety of Intravitreal Injection Guide. Journal of VitreoRetinal Diseases. 2018;2(1), 26–31. https://doi.org/10.1177/2474126417728622
  11. Tailor R, Beasley R, Yang Y, et al. Evaluation of patients’ experiences at different stages of the intravitreal injection procedure – what can be improved?. Clin Ophthalmol. 2011;5:1499‐1502. doi:10.2147/OPTH.S24358
  12. Sanabria MR, Montero JA, Losada MV, et al. Ocular pain after intravitreal injection. Curr Eye Res. 2013;38(2):278‐282. doi:10.3109/02713683.2012.758290
  13. Grzybowski A, Told R, Sacu S, et al. 2018 Update on Intravitreal Injections: Euretina Expert Consensus Recommendations. Ophthalmologica. 2018;239(4):181‐193. doi:10.1159/000486145
  14. The Royal College of Ophthalmologists. College Statement on intra-ocular injections by non-medical health care professionals (HCPs). April 2013.
  15. Simcock P, Kingett B, Mann N, et al. A safety audit of the first 10 000 intravitreal ranibizumab injections performed by nurse practitioners. Eye (Lond). 2014;28(10):1161‐1164. doi:10.1038/eye.2014.153
  16. Rasul A, Subhi Y, Sørensen TL, et al. Non-physician delivered intravitreal injection service is feasible and safe – a systematic review. Dan Med J. 2016;63(5):A5229.
  17. Foot B, MacEwen C. Surveillance of sight loss due to delay in ophthalmic treatment or review: frequency, cause and outcome. Eye (Lond). 2017;31(5):771‐775. doi:10.1038/eye.2017.1
  18. Waqar S, Ayaz A, Karamat I, et al. A novel device for rapid, safe and precise delivery of intravitreal injections. BMJ Innovations 2019;5:8-12.
  19. Waqar S. Comment on: Optimisation of intravitreal injection technique using a Barraquer speculum with solid flat blade and finger stabilisation. Eye (Lond). 2019;33(3):512. doi:10.1038/s41433-018-0248-3
  20. National Institute for Health Research. https://www.crd.york.ac.uk/crdweb/ShowRecord.asp?ID=22013015682&ID=22013015682. Accessed 6/5/2020
  21. GIRFT Programme National Specialty Report – Ophthalmology. December 2019.
  22. Hollingworth W, Jones T, Reeves BC, et al. A longitudinal study to assess the frequency and cost of antivascular endothelial therapy, and inequalities in access, in England between 2005 and 2015. BMJ Open. 2017;7(10):e018289. doi:10.1136/bmjopen-2017-018289
  23. Subhi Y, Kjer B, Munch IC. Prefilled syringes for intravitreal injection reduce preparation time. Dan Med J. 2016;63(4):A5214.