Letter to the Editor: Intravitreal injections. Who should perform them?


In response to a previously published article, three ophthalmologists present their views on intravitreal pharmacotherapy injections.

Intravitreal pharmacotherapy injections. Who should perform them?

The rapid development and widespread adoption of intravitreal pharmacotherapy for the treatment of neovascular age-related macular degeneration (nAMD), and macular oedema due to diabetic retinopathy (DMO) and retinal vein occlusions (RVO) has significantly improved the visual outcomes for patients with these disorders. Unfortunately, the total number of injections necessary to treat the large cohorts of afflicted patients has challenged physicians’ offices, healthcare systems, and operating room schedules, particularly outside of the United States where access to care may be in shorter supply. This may result in vision loss due to delayed diagnoses and initiation of therapy, as well as decreased access to specialized ophthalmic care for other needy patients.

In the article "The rationale for enabling nurses to inject dexamethasone implants," Raman proposed that allied health care professionals (AHP; nurses, optometrists, and orthoptists) in the United Kingdom begin administering dexamethasone inserts (DEX) for the treatment of DMO and RVOs.1 He argues that public health services, such as the United Kingdom National Health Service, have insufficient physicians to deliver the number of injections required to treat all patients. In response to this labor shortage, trained nurses have administered intravitreal anti-vascular endothelial growth factor (VEGF) drugs in the United Kingdom with purportedly low complication rates, so the addition of the more technically challenging DEX injection may be possible. Whereas Raman believes that the role of AHP should be expanded to include DEX injections, we believe that this model should be closely scrutinized before being adopted in other countries.

Related: Clinical results analyze dexamethasone implant effect on macular thickness

The AHP injection model has been implemented in the UK and other jurisdictions, not because it was believed to add quality to healthcare delivery, but because of several healthcare system deficiencies. As Raman states “resource constraints do not permit clinicians to deliver the injections themselves, as this would lead to a shortfall in clinical and surgical activity.Additionally, he states that the “protracted waiting time for patients after making the clinical decision to move forward with the procedure…sometimes exceeded 30 days” and “dexamethasone injections were delivered in the operating theater.

Several of Raman’s statements need to be addressed to emphasize important differences in the delivery of medical retina care in the UK and US. Specifically, he references limited access to physicians and long waiting times for the operating room, both of which delay the initiation of care. The US has more ophthalmologists per capita than has the UK,2 which enables patients to access physicians more rapidly. In addition, patients in the US with new symptoms suggestive of nAMD are able to make appointments directly with comprehensive ophthalmologists and retina specialists, whereas patients in the UK public healthcare system need to first see primary care providers (general physicians or optometrists) from whom they may be referred to retinal providers.3

Related: DMO study shows robust efficacy of intravitreal dexamethasone implant

In the UK, the time between making the clinical decision and performing the injection in the operating theater may be up to 30 days but in the US physicians frequently initiate therapy in the outpatient clinic the same day. The time added to a physician’s schedule for an unexpected anti-VEGF or DEX injection is negligible and most physicians, even those who perform most of their procedures in “injection clinics”, perform the first injections immediately. Performing injections in the office is much more efficient and much less expensive than moving them to the operating theater. The operating room is a high-tech, high-cost environment that is suited well for complex, lengthy procedures, but access to space is often competitive, particularly in national health systems.

Related: Anti-VEGF therapy for retinal disease (video)

Raman states that the safety of AHP injections has been amply demonstrated, but he references only two ophthalmologic studies and most of his references pertain to non-ophthalmologic procedures. The study by Simcock et al.4 was a safety audit that makes no mention of data acquisition, leaving us to wonder if this was a retrospective study. The authors reported a low rate of endophthalmitis, no cases of lens touch, but one case (0.01%) of a “large conjunctival hemorrhage”, which is three orders of magnitude less than the 11% incidence reported in other studies.5 This makes one question the accuracy and completeness of this “audit” study.

Bolme et al.6 performed a prospective trial in which patients with nAMD, DMO, and RVO were randomized to receive injections by nurses or physicians. At the 1-year primary endpoint, patients treated by nurses had similar visual acuity (VA) improvements as those treated by physicians (+0.7 vs. +1.6 letters; P = 0.019 (study sample)). The mean VA gains were far less than those usually seen in nAMD (6-10 letters), DMO (11-13 letters) and RVO (14-18 letters) registration trials, which makes one question the effectiveness of the therapy. The unclear methodology and unusual results from these two referenced studies do not support Raman’s assertion that AHP- delivered injections are as safe and effective as those performed by physicians.

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Data comparing costs between AHP-delivered injections in the UK and physician-delivered injections in the US has not been published, but the high cost associated with the use of the operating theater is undoubtedly much more than for the outpatient clinic. Since US retina specialists almost exclusively perform injections in the outpatient clinic, the cost of injections in the US would not be lowered by following the UK model.

Raman suggests that AHP perform DEX injections but neither he nor the referenced articles discuss who manages the patients. Many people focus on the technical aspects of an ophthalmic procedure but experts rightfully claim that pre-operative and post-operative patient management is a far more sophisticated process. Who to treat, when to treat, and with what to treat, are more important and difficult decisions than those pertaining to the nuances of needle placement. Transitioning to AHP injections risks suboptimal patient management and may compromise outcomes. Unless a robust management regimen includes regular evaluations by fellowship-trained physicians, visual outcomes are likely to suffer as shown by the inferior VA improvements in patients treated by nurses.6

Related: Study examines anti-VEGF treatment lapses in retinal vein occlusion

So how do we balance the experience of Raman and others in the UK and other parts of the world with the needs of patients within the US. Firstly, the US does not face the same access limitations that exist in other parts of the world, so having patients managed and treated by the highest trained and most experienced providers makes the most sense. Secondly, office-based injections as performed in the US are much less expensive, more efficient, and do not require an AHP as has been noted in the UK. Thirdly, until well designed, prospective trials unequivocally show that an AHP model produces comparable visual and safety results to a physician model, expansion of procedural privileges to AHP in the US should not be considered.

Michael W. Stewart, MD
Professor and Chairman of Ophthalmology
Mayo Clinic Florida
Jacksonville, FL
Adam M. Katz, MD
Center for Advanced EyeCare
Vero Beach, FL
Mark Michels, MD
Retina Care Specialists
Palm Beach Gardens, FL
Raman V. Should nonclinicians inject dexamethasone implants? Ophthalmology Times 2021;46(6).
International Council of Ophthalmology. Number of Ophthalmologists in Practice and Training Worldwide. Accessed 8/2/2021. http://www.icoph.org/ophthalmologists-worldwide.html.
Riad SF, Dart JKG, Cooling RJ. Primary care and ophthalmology in the United Kingdom. Br J Ophthalmol 2003;87(4):493-499.
Simcock P, Kingett B, Mann N, Reddy V, Park J. A safety audit of the first 10,000 intravitreal ranibizumab injections performed by nurse practitioners. Eye (Lond). 2014;28(10):1161-1164.
Yun C, Oh J, Hwang S-Y, Kim S-W, Huh K. Subconjunctival hemorrhage after intravitreal injection of anti-vascular endothelial growth factor. Graefes Arch Clin Exp Ophthalmol 2015;253(9):1465-1470.
Bolme S, Morken TS, Follestad T, Sørensen TL, Austeng D. Task shifting of intraocular injections from physicians to nurses: a randomized single-masked noninferiority study. Acta Ophthalmol 2020;98(1):139-144.

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