Systemic Immunosuppression and Risk of Endophthalmitis

Systemic Immunosuppression and Risk of Endophthalmitis

September 27, 2022
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Eyes receiving intravitreal anti-VEGF injections who are concurrently on systemic immunosuppressive therapy may be at an increased risk for developing PIE.

However, final visual outcomes following post-injection endophthalmitis treatment is similar regardless of systemic immunosuppression status. Additional studies are indicated to further elucidate the role, if any, of immunosuppressive therapy in the management of PIE.

Transmission of oral flora through respiratory droplets is particularly concerning during intravitreal injection. PIE is a dreaded complication and refers to specific endophthalmitis developing following the intravitreal administration of drug injections, most commonly being anti-vascular endothelial growth factor (anti VEGF) agents.

It is not uncommon in today's era when the use of anti-VEGF drugs is wide-spread and a very commonly performed out-patient procedure in clinical ophthalmic practice. Its incidence is between 0.028- 0.056% and does not appear to vary based on geographic location.

PIE is a clinical diagnosis and antimicrobial drugs need to be started on an empirical basis and systemic and local therapy should be initiated as early as possible.

An ultrasound B-scan will confirm the inflammatory component of the condition. AC tap, vitreous tap, or a vitreous biopsy can be taken to ascertain the microorganism causing endophthalmitis, and treatment given accordingly.

The use of intravitreal anti-VEGF injections are the standard of care for the treatment of common retinal diseases.

These include neovascular age-related macular degeneration, retinal vein occlusion, and diabetic macular edema. Although anti-VEGF medications have excellent safety profiles, acute bacterial endophthalmitis remains an uncommon but potentially devastating complication.

Multiple studies have evaluated procedure-related risk factors associated with postinjection endophthalmitis. Patients taking immunosuppressive medications have an increased risk for endogenous endophthalmitis.


To evaluate the effect of systemic immunosuppression on the rates and outcomes of endophthalmitis after intravitreal anti-VEGF injections.


A retrospective, single-center, comparative cohort study.


All eyes receiving intravitreal anti-VEGF (bevacizumab, ranibizumab, and aflibercept) injections from January 1, 2016 to September 1, 2019 were included in this study. The trial investigators used billing records and endophthalmitis logs to identify patients who developed endophthalmitis following the injections.

They reviewed the charts of all patients who were treated for endophthalmitis, and confirmed the diagnosis. Endophthalmitis was defined as patients who presented with a clinical suspicion that was high enough to warrant either intravitreal antibiotic injection with vitreous/aqueous tap or pars plana vitrectomy with injection of antibiotics.

The investigators divided the cases into an “immunosuppression” group and a “no immunosuppression” group. They defined the immunosuppression group as any patient taking systemic medication from the following classes at the time of intravitreal injection: corticosteroids, alkylating agents, antimetabolites, calcineurin inhibitors, mammalian target of rapamycin (mTOR) inhibitors, biologics, monoclonal antibodies, and chemotherapeutic medications.

The primary outcome measure was the rate of endophthalmitis in the immunosuppression group and no immunosuppression group. Secondary outcome measures included visual acuity (VA) outcomes and microbiologic flora in both groups.


Of 269,047 intravitreal injections administered over the study period, 1300 (0.48%) patients were taking a systemic immunosuppressive medication at the time of the causative injection.

Five of 1300 (0.38%; 1 in 260 injections) cases of endophthalmitis occurred in the immunosuppression group, and 100 of 269,047 (0.037%; 1 in 2690 injections) cases occurred in the no immunosuppression group (odds ratio, 9.86; 95% CI, 4.0-24.2; P < .001).

Of the 5 cases of presumed endophthalmitis in the immunosuppression group, 4 patients were taking oral prednisone and 1 patient was taking mycophenolate mofetil at the causative injection. Three of 5 (60%) eyes in the immunosuppression group were culture positive compared with 32 of 74 (43%) cases in the no immunosuppression group (P = .650).

Patients with presumed endophthalmitis presented a mean (SD) 2.8 (1.9) days after injection in the immunosuppression group compared with 5.3 (5.4) days in the no immunosuppression group (difference, 2.51 days; 95% CI, 0.15-4.87; P = .040).

Mean (SD) logMAR (Snellen equivalent) VA at endophthalmitis presentation was 2.11 (1.2; approximately 20/2500) in the immunosuppression group vs 1.8 (0.91; approximately 20/1260) in the no immunosuppression group (P = .465).

At 6 months after endophthalmitis treatment, mean (SD) logMAR VA was 1.22 (1.3; approximately 20/330) for the immunosuppression group compared with 0.96 (0.93; approximately 20/180) for the no immunosuppression group (adjusted difference, 0.253; 95% CI, –0.99 to 0.48), P = .494).


Patients taking systemic immunosuppressive medications undergoing intravitreal injections may be at increased risk of postinjection endophthalmitis and may have earlier symptom onset. However, visual outcomes were similar between the 2 groups 6 months after endophthalmitis treatment.