Study: Intravitreal Injection Complications Decrease With Number of Prior Injections

The study also shows younger and female patients are more likely to report complications.

The risk of complication from intravitreal injections (IVI) is negatively correlated with the number of previous injections, according to a report published in Ophthalmology Retina

Researchers report several discoveries about complications associated with intravitreal injection. They include a 32% increased risk for female patients of presenting with complications compared with male patients.

Additionally, the data shows that complication rates vary among injection providers, and younger patients are more likely to report experiencing serious complications than older patients.

The researchers sought to quantify the frequency of patient-reported complications related to injections of anti-vascular endothelial growth factor (VEGF) agents bevacizumab, aflibercept, and ranibizumab (0.3 mg and 0.5 mg) as well as steroidal agents triamcinolone acetonide, dexamethasone implant, and fluocinolone acetonide implant.

They identified 44,734 injections of these agents in 5318 adult subjects (median age of 75.7 years at injection, 2987 females) that 16 providers administered from 2012 to 2016 at the Cleveland Clinic Cole Eye Institute. The providers administered a range of 141 to 6027 injections (median of 2416 injections administered).

The researchers screened for patients who had an ophthalmology-related encounter – including office visits, emergency department visits, phone call or Epic electronic messages – within 15 days of the injection date.

Excluding scheduled follow-ups or surgeries and endophthalmitis cases, they discovered that there were 841 injections that had at least 1 IVI-related complication within the 15-day window. The researchers divided the complications into “minor” (ones that did not require intervention or observation), “serious” (required intervention or close observation), and “unrelated.” The unrelated complications appeared to be due to disease progression. They identified 1031 unique complications from 685 patients who presented in 841 encounters, of which 81% had only 1 complication. The overall rate of complications was 1.9% of total injections or 12.9% of all patients who received injections.

Minor complications were most frequent (612, 1.4% of all injections) form of complication, and those were mostly irritation (312) and subconjunctival hemorrhage (284). The most common types of serious complications (157, .4% of all injections) were corneal abrasion (46) and iritis (31).

The treatment of post-injection medications decreased the risk of irritation (P =.045) and subconjunctival injection of lidocaine increased the risk of subconjunctival hemorrhage (P =.005).

The complication rate experienced by each provider ranged from 1.00% to 5.67%, which suggests subtle differences in each provider’s injection administration that were not reported in the electronic medical record (EMR) system, which could include use of a lid speculum or duration of eye rinse after the injection, the researchers said.

“The number of total injections performed by each provider also varied, which may play a role in the different complication rates,” according to the researchers. “A provider who focuses discussion on anticipation of the most common complications may lead to fewer complication presentations. Unlike previous studies which relied on provider surveys to associate injection protocol parameters with complications, our study relied on data reported in our EMR system. It is interesting to note the provider has a large influence on complications, and we caution the sole use of provider surveys to document injection protocol parameters.”

Limitations of the study include the inability to standardize the post injection instructions given by providers, which may have influenced patient encounters, the researchers said. The retrospective nature of the study and the involvement of self-reporting also may have led to underreporting of complications, they noted.

Complication rates for these injections in routine clinical practice are low at approximately 1.9%, and serious complication rates are even lower. “Most complications can be adequately handled by phone,” the study explains.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Ramos MS, Xu LT, Singuri S, et al. Patient-reported complications after intravitreal injection and their predictive factors. Ophthalmology Retina. Published online October 12, 2020.