The COVID-19 Pandemic and Intravitreal Injections

Dear colleagues,

Due to the COVID-19 pandemic, we are experiencing extraordinary times, nationally and globally. As ophthalmologists, we are performing the designated emergency procedures while trying to postpone elective procedures in order to protect our patients, ourselves, and other healthcare workers. However, during this period we are having difficulties determining the place of the intravitreal injection therapies that were done so frequently in retina clinics before the pandemic. These injections definitely cannot be classified as elective procedures, but also cannot exactly be classified as emergency procedures that must be performed immediately. It would be more accurate to include these treatments in a “priority” procedures category. This article discusses the intravitreal injection practices worldwide and approaches the subject from two different points of view, patient and doctor.

In their COVID-19 review dated March 20, 2020, the American Society of Retina Specialists (ASRS) reported that a significant percentage of retina patients are at risk of permanent vision loss and require regular intravitreal injection therapy, and therefore have special circumstances during the pandemic. Because the patients who usually require these injections are elderly and may have weaker immune systems and comorbid systemic diseases, they are at high risk of morbidity and mortality associated with COVID-19. When retina specialists decide whether a patient’s visit is necessary, they evaluate the patient’s risk of exposure to infection against the risk of vision loss that may occur without treatment. According to ASRS, this evaluation depends on the region and the local prevalence of infection.

From the patient’s perspective:

Globally, the age group most at risk in the COVID-19 pandemic is people over 65 years old. Intravitreal injections are usually used in the treatment of age-related macular degeneration (AMD), diabetic macular edema (DME), and macular edema associated with central/branch retinal vein occlusion (CRVO/BRVO), conditions that mainly affect the patients in this age group. Our older patients may feel as if they have to make a choice between their lives and their visual acuity, and therefore may be avoiding presenting to ophthalmology clinics. However, these treatments must be administered regularly, and without them these patients may suffer severe vision loss. Moreover, if the patient’s other eye was previously affected and has low vision or is scarred, the potential delay in treatment can result in the patient’s vision deteriorating to the level of legal blindness, resulting in permanent morbidity. On the other hand, the possible contact and exposure while presenting for routine examination put patients at risk of being affected by this severe disease. Even if precautions are taken to minimize in-hospital contact, the risk is not limited to the hospital environment but includes the entire time from the moment the patient leaves their home to when they return home. In fact, the risk of infection is particularly high in this population because patients with severe vision loss cannot drive and either need someone to take them to the hospital or must use other modes of public transport.

From the doctor’s point of view:

Preventive medicine is the foundation of medical practices. Therefore, while we are responsible for taking all possible precautions to reduce contact during admission, we must also decide on a case-by-case basis, considering other comorbidities, which patients should actively continue to receive injections and then perform the necessary injections in those patients. However, implementing these precautions and decisions may not be as easy as it seems. These precautions and practices can be categorized in three basic groups: before examination, during examination, and during injection.

1.     Precautions before examination:

The patient should call the clinic and talk to their doctor before their visit. Treatment indication can be evaluated on an individual basis to decide whether the visit is necessary. For example, for patients whose vision has been stable for some time, the process can be evaluated together with the patient and the visit can be postponed to a later date. The patient may be asked to self-monitor by evaluating their vision daily. Neovascular AMD poses the greatest problem if the visit is postponed. DME follows a milder course after the first year. While retinal vein occlusions sometimes require intensive treatment, they may also have different prognoses that have less need for regular injections.

2.     Precautions during examination:

Patients' relatives should not be admitted to the clinic except when absolutely necessary, and the patient should be evaluated for COVID-19 symptoms, including measuring body temperature, upon entrance to the clinic. In suspicious cases, the patient should be referred directly to COVID outpatient clinics. Patient appointments should be scheduled such that the minimum number of patients is present in the clinic at any given time. Crowding of waiting rooms must be avoided and seating must be arranged according to social distancing guidelines. In addition, materials such as newspapers and magazines that may be objects of common contact in patient waiting rooms should be removed.

Regarding the examination of patients receiving regular intravitreal injection therapy, Frank G. Holz, president of the European Retinal Society (EURETINA), stated that at the University of Bonn Eye Clinic, patients not reporting decreased vision should continue to receive monthly injections without visual acuity, slit-lamp biomicroscopy, fundoscopy, or OCT examinations, while other patients should be scheduled for 2-month treatment intervals in the hope that everything returns to normal, and patients are recommended to check themselves for any changes in vision.

In their update on March 30, 2020, the Royal College of Ophthalmologists recommended classifying patients receiving active anti-VEGF therapy by treatment indication and scheduling their visits accordingly. Within this scheduling framework, they recommended that for neovascular AMD patients, anti-VEGF therapy should continue every 8 weeks without clinical examination unless there is significant vision loss; for DME patients, anti-VEGF injections should be postponed and visits scheduled 4 months later (except for eyes with severe nonproliferative diabetic retinopathy and active proliferative diabetic retinopathy that may require anti-VEGF agents and panretinal photocoagulation [PRP]); for patients with BRVO, visits should be postponed for 4 months, while for CRVO patients, PRP should be considered if macular edema persists after more than 6 injections, otherwise the examination visit should be scheduled 4 months later.

The Netherlands Ophthalmological Society’s Working Group on Medical Retina published a 4-step recommendation list. The first step contains organizational suggestions regarding the administration of intravitreal injection therapy. In the second step, they outlined how to reduce numbers of intravitreal injections and contact with personnel, while the third step included additional measures to reduce contamination risk. In the fourth step they created an action plan on what to do if capacity is exceeded. In this framework, they emphasized that intravitreal injection is not an elective procedure and recommended that first and foremost, all patients should be contacted the day before injection and questioned about COVID symptoms, and any patients with suspicious symptoms should have their injection postponed for 14 days. They stated that in order to reduce contact, continuing injections at the most recently specified intervals without visual acuity measurement and OCT imaging would be appropriate except in special cases. Similarly, Sebastian Wolf from Bern University Eye Clinic recommended for patients continue to receive injections at their normal interval if they show no decrease in vision since the last injection, and every 4 weeks otherwise. Although it varies based on the clinic conditions, performing more than 20 injections in half of a working day is not recommended.

Jose Garcia-Arumi from Valle de Hebron Hospital in Barcelona reported that treatment indications for anti-VEGF injections are more strict; they perform anti-VEGF therapy in patients who are receiving the loading dose for neovascular AMD and had an initial visual acuity ≥0.1, patients with a single eye and have a treatment interval of less than 6 weeks in the treat and extend regimen, and patients whose laser photocoagulation therapy must be postponed but are at risk of neovascular glaucoma. They stated that treatment can be postponed in patients with advanced AMD and a treatment interval of more than 4 weeks, patients with an initial visual acuity < 0.1 and receiving a loading dose, and patients on maintenance therapy with stable vision in two consecutive visits and receiving fixed-dose injections.

As can be seen, treatment indication includes the absolute treatment of patients at risk of severe vision loss, and the stringency of these indications can vary regionally based on the extent of the outbreak.

3.     Precautions during intravitreal anti-VEGF injection:

1.     Patients should be admitted to the clinic alone when possible, or with one companion at most.

2.     The minimum number of patients should be present in waiting and preparation rooms and care should be taken to ensure social distance between patients to prevent contact.

3.     It is absolutely required for patients and companions to wear protective masks.

4.     All physicians and other healthcare workers must be in full personal protective equipment (mask, gloves, gown, and goggles).

5.     Non-contact tonometry should not be performed after injection.

6.     It should be ensured that patients whose injections are complete leave the hospital environment promptly.

In conclusion, considering the approaches and experiences of different clinics, in addition to planning the necessary protective measures for us, our healthcare team, and patients, we must plan necessary treatments according to our clinical conditions and our patients’ status, and keep lines of communication open with them.

We wish you all happier and healthier times in which we overcome the COVID-19 pandemic.

Dr. Figen Şermet

Turkish Ophthalmological Association

Medical Retina Society