What to Do When Patients Refuse Injections

Micropulse laser may be an option.

By Caesar K. Luo, MD

The prospect of having a needle stuck directly into one’s eye is, at best, disconcerting to patients. When faced with potential for vision loss, however, most patients will accede to intravitreal injections, whether anti-VEGF or corticosteroid therapy. Based on published clinical studies, as well as personal experience, anti-VEGF agents produce the fastest and most robust results in the treatment of macular edema.

But what can be done for the patient who refuses injections due to extreme physiologic reactions such as heart palpitations and fainting? Or the younger patient who cannot afford the temporary blurry vision that may follow an injection because of work requirements? One answer may be micropulse laser therapy performed with the IQ 532 laser (Iridex), a safe and effective alternative treatment for patients who would rather refuse treatment than undergo ocular injections.


With few exceptions, I recommend to my patients who present with diabetic macular edema (DME) a treatment plan of frequent and repeated injections, based on the protocol established by the Diabetic Retinopathy Clinical Research Network (DRCR.net).1 I believe this regimen offers the best prognosis for improved vision in the long term, and science shows us that this treatment is superior to traditional continuous-wave (CW) laser therapy,2 which is known to cause retinal burns and cellular damage.

For patients with severe or diffuse DME, or with 20/50 or worse BCVA, I begin treatment with intravitreal injections of aflibercept (Eylea, Regeneron). Those with mild to moderate edema receive bevacizumab (Avastin, Genentech) on a monthly injection schedule for 3 months. If a minimal or worsening response occurs, I immediately consider another option, such as intravitreal corticosteroids. As long as the patient improves, I continue injection therapy.

When a fully compliant patient who has maintained the recommended schedule of anti-VEGF or corticosteroid injections shows significant reductions in fluid levels and macular thickness on optical coherence tomography (OCT), I recommend adding micropulse laser therapy as a supplement to injections. I explain to patients that this laser treatment can potentially reduce the burden of future injections and the likelihood of tachyphylaxis or atrophy, which can occur after years of repeated injections. I have had good results using this protocol, and many patients no longer require injections after the laser treatment.


Micropulse laser therapy uses a mechanism different from that of CW laser photocoagulation. Administration of repetitive short pulses at a 5% duty cycle (compared with 100% duty cycle with CW) allows tissue to cool between pulses, reducing the thermal damage and tissue destruction seen with CW application. The low-intensity pulses stimulate a stress response, inducing beneficial intracellular biological factors that are primarily antiangiogenic and restorative without causing the tissue damage seen in CW.3 Rather than destroying tissue to stop leakage, this laser modality stimulates viable tissue to produce antiangiogenic inhibitors while simultaneously impeding VEGF production. The therapy works at the cytokine level to incite restorative intracellular biological activity; therefore, results tend to take a few months before showing marked improvement.


Some patients, such as women who are pregnant or breastfeeding, are understandably unwilling to initiate injections. There is also a subset of patients who adamantly refuse injections and are even more averse to surgery. In the past, I immediately recommended that patients with these types of objections seek a second medical opinion, as the decision to forego treatment may result in permanent vision loss.

Anti-VEGF therapy is a mainstay of treatment for DME, based on data we have now. However, since incorporating micropulse technology with the IQ 532 laser into my practice, I can confidently offer this as a safe, noninvasive, effective alternative to patients who otherwise might receive no treatment at all. Data show that micropulse laser is safe and effective and can be performed over the fovea,4 and patients like the laser because it is not an injection.

I do not offer this option as a primary therapy unless a patient will not consider injection therapy; in general, I believe patients have a more robust response to micropulse laser after the edema and retinal volume have decreased.

Several of my patients who refused injections have had impressive results with micropulse therapy as primary therapy. One case involved the mother of a staff member who presented with recent onset DME (Figure 1). She absolutely refused injections, ignoring advice from her daughter and me, but she agreed to try micropulse. She returned 1 month later with complete resolution of edema and with improved vision (Figure 2). I was pleased with the outcome, and the patient was happy to receive this noninvasive but effective treatment.

Figure 1. OCT image of patient with early-onset DME; central foveal thickness is 295 μm, and visual acuity is 20/50.

Figure 2. OCT image 6 weeks after a single micropulse laser treatment; the patient’s central foveal thickness had decreased to 256 μm, and visual acuity improved to 20/40.


As yet, no head-to-head clinical comparison between anti-VEGF therapy and micropulse laser has been published, so we have no data showing that one treatment is superior or equal to the other. Until conclusive data are published, and because patients like to see the prompt results that injections often bring, my preference is to begin with injection therapy to reduce edema as quickly as possible and then use micropulse to maintain.

However, micropulse therapy as a primary therapeutic regimen may be on the horizon. We know that not every patient fits clinical trial parameters, and that not everyone tolerates injections due to psychologically rooted or physical problems, including adverse reactions to povidone-iodine or to the medication itself. We need to be able to offer these types of patients other options.

My goal is always to begin therapy with anti-VEGF injections for patients with macular edema. When injections are not an option, micropulse laser therapy can be a viable and effective alternative. n

1. Wells JA, Glassman AR, Ayala AR, et al; Diabetic Retinopathy Clinical Research Network. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015;372(13):1193-1203.

2. Lavinsky D, Cardillo JA, Melo LA Jr, et al. Randomized clinical trial evaluating mETDRS versus normal or high-density micropulse photocoagulation for diabetic macular edema. Invest Ophthalmol Vis Sci. 2011;52(7):4314-4323.

3. Yu AK, Merrill KD, Truong SN, et al. The comparative histologic effects of subthreshold 532- and 810-nm diode micropulse laser on the retina. Invest Ophthalmol Vis Sci. 2013;54(3):2216-2224.

4. Luttrull JK, Sinclair SH. Safety of transfoveal subthreshold diode micropulse laser for fovea-involving diabetic macular edema in eyes with good visual acuity. Retina. 2014;34(10):2010-2020.

Section Editor Derek Kunimoto, MD, JD
• comanaging partner, Retinal Consultants of Arizona; director, Scottsdale Eye Surgery Center, Scottsdale, Ariz.

Caesar K. Luo, MD
• owner, Progressive Vision Institute, Philadelphia
• financial disclosure: speaker for Alimera Sciences and Iridex; advisory board for Alimera Sciences and Allergan


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