Intravitreal Injection Complication Rates Low in Real-World Study

In a real-world setting, complication rates associated with intravitreal injections (IVI) are low compared with clinical trial reported data, according to research results published in Ophthalmology Retina. 

Because there is a lack of pragmatic research related to IVI-related noninfectious complications, researchers conducted a retrospective cohort study evaluating the complication rate at a high-volume tertiary eye care center. Additionally, the researchers sought to identify potential risk factors associated with complication development. 

A total of 44,734 injections of 8 common intravitreal agents, including 4 anti-vascular endothelial growth factor (anti-VEGF) agents and 4 steroidal agents were identified. Investigators screened for patients who had ophthalmology encounters within 15 days of the injection date. For all participants, baseline data, intravitreal agent, number of previous injections, and provider data were collected. 

Investigators divided complications into 3 groups: minor, serious, and unrelated. Patients with endophthalmitis were excluded, although 19 such cases were identified for a rate of 0.042% or 1:2355 injections. 

Between 2012 and 2016, a total of 44,734 injections were made in 5318 unique patients (56% women; 80% white) at a single institute. Median age at injection was 75.7 years (interquartile range [IQR], 65.1 to 84.2 years). Right and left eye injections were split evenly — 37% each — with 26% of injections were same-day bilateral injections. 

Among all injections, 95% used anti-VEGF (bevacizumab, 54%). Spanning the 5-year study period, the median number of injections per patient was 5 (range, 1 to 110). Sixteen unique providers, with a median number of injections per provider of 2416, were administered (range, 141 to 6027). 

During the study period, 1031 unique complications from 685 patients were seen across 841 encounters. Of these, 81% included only 1 complication. In 66% of the encounters, patients first sought treatment by telephone or electronic health record electronic message. Among these initial encounters, 63.4% were resolved; 29.2% required a scheduled follow-up visit, and 7.4% led to the patient initiating an unscheduled urgent visit. Office visits and emergency department visits represented 32% and 2% of encounters, respectively. 

The overall complication rate was 1.9% of total injections, with 12.9% of injected patients experiencing at least 1 complication. The most common complications were minor (1.4% of all injections), and included irritation and subconjunctival hemorrhage (SCH). Serious complications accounted for 0.4% of all injections; corneal abrasion was the most common. Unrelated complications were seen in 0.3% of total injections. 

Odds of experiencing any complication were increased for women, and decreased with additional injections. Complications varied greatly among different providers, with complication rates ranging from 1% to 5.67%. Most showed a rate of 2%. 

Investigators also looked at complications that were represented in higher frequencies, including irritation, subconjunctival hemorrhage, and serious complications (n=312, 284, and 157, respectively). After adjusting for confounders, results of a regression analysis showed that most protocol parameters were not associated with either irritation or SCH. The use of subconjunctival lidocaine injection increased the risk of SCH. 

Medications that patients received in the clinic following injection included antibiotic drops. Patient gender, number of previous injections, and provider demonstrated a statistically significant effect across protocol parameters. For women, risks for irritation and SCH were consistently increased; however, these risks decreased with each additional injection. 

No associations were found for any serious complications with injection protocol parameters, while patient gender no longer impacted risk. The number of previous analyses, however, remained a significant factor. As patient ages increased, the risk for any serious complication decreased. 

Study limitations include potential underreporting of complications due to the retrospective, self-reported nature of the study, as well as an inability to standardize the instructions for after injections given by providers. 

“Complication rates seen in routine clinical practice are low,” the researchers conclude. “Serious complication rates overall are very low, and most complications can be handled adequately by telephone or Epic electronic message.” 

“Through this analysis of IVI-related complications, we hope to prepare providers better to achieve the best possible outcomes for their patients.”


Ramos MS, Xu LT, Singuri S, et al. Patient-reported complications after intravitreal injection and their predictive factors. Ophthalmol Retina. 2021;5(7):625-632. doi:10.1016/j.oret.2020.09.024