Injection-related Endophthalmitis Research Articles

Posterior vitreous attachment as a risk factor for endophthalmitis following intravitreal antivascular endothelial growth factor injection.

To evaluate the importance of the status of posterior vitreous in eyes with endophthalmitis following intravitreal anti-vascular endothelial growth factor (anti-VEGF). The absence or existence of posterior vitreous detachment (PVD) was elicited in 23 eyes of 23 patients with injection related endophthalmitis, during pars plana vitrectomy (PPV) and compared with 24 control eyes of 24 patients who received intravitreal anti-VEGF without any complication. Thirtten (54.2%) out of 24 patients in the control group had full PVD, whereas only 2 (9.5%) out of 23 eyes in endophthalmitis group (p < 0.001) had full PVD. In all eyes without PVD, posterior vitreous was inducted to be detached at least from optic nerve and macular area without any iatrogenic tear. The absence of PVD is a factor that increases the risk of endophthalmitis after intravitreal injections. Uncomplicated separation of the posterior vitreous from the retina in PPV contributes to better prognosis.

Reduced Incidence of Intravitreal Injection-Related Endophthalmitis With Prefilled Syringes.

Purpose: To evaluate the incidence and clinical characteristics of intravitreal injection-related endophthalmitis cases with antivascular endothelial growth factor (anti-VEGF) medications manufactured as prefilled syringes or non-prefilled preparations. Methods: This retrospective chart review comprised eyes that received intravitreal anti-VEGF at a single-specialty retina practice from January 1, 2014, to December 31, 2019. Eyes diagnosed with injection-related endophthalmitis were identified. Demographic and clinical data were abstracted from medical records, including the type of anti-VEGF agent, baseline and follow-up corrected visual acuity (VA), and microbiologic findings. Results: The review identified 88 cases of intravitreal anti-VEGF injection-related endophthalmitis and 325 990 total injections. Total injections included 32 045 (9.8%) bevacizumab (BEV), 93 073 (28.6%) ranibizumab (RAN), 122 947 (37.7%) aflibercept (AFL), and 77 925 (23.9%) ranibizumab prefilled syringe (RANPFS). Ten of the endophthalmitis cases were related to BEV, 21 to RAN, 45 to AFL, and 12 to RANPFS. The endophthalmitis rate was lowest for RANPFS (0.0154%) (BEV, 0.0312%; RAN, 0.0226%; AFL, 0.0366%) (P = .030). Thirty-four (41.5%) of 82 samples were culture positive. RANPFS had a significantly lower rate of culture-proven postinjection endophthalmitis than the other agents (P = .003). The mean VA for endophthalmitis cases related to RANPFS vs non-prefilled agents was similar at presentation (Snellen 20/2092 vs 20/2327) and at the 3-month follow-up (Snellen 20/201 vs 20/272) (both P > .05). Conclusions: Anti-VEGF medications in prefilled syringes may reduce the risk for medication contamination during injection preparation. RANPFS was associated with a lower rate of injection-related endophthalmitis than non-prefilled anti-VEGF medications.

Preventive factors, diagnosis, and management of injection-related endophthalmitis: a literaturereview.

BackgroundIntravitreal medication injections represent the gold standard treatment for a variety of potentially blinding chorioretinal vascular diseases. Despite their excellent safety profile, they are associated with the feared complication of injection-related endophthalmitis (IRE). Though the overall incidence of IRE is low, due to the ever-increasing number of injections being performed, it is a complication that all retina specialists are likely to encounter. This article reviews various factors that could potentially influence the risk of IRE and discusses evidence-based strategies for management.MethodPubMed was searched for keywords “intravitreal injection” and “endophthalmitis” from the period of 1995–2021. Relevant articles were reviewed and selected articles were analyzed with respect to the incidence, potential preventive factors, clinical presentation, microbial profile, management, and outcomes for IRE.ResultsThere is strong consensus supporting the use of povidone iodine topical antiseptic, eyelid retraction away from the injection site, and avoiding treatment of eyes with active surface or eyelid disease, but there is less agreement on the use of face masks versus “no-talking” policies and optimal anesthetic technique. Current evidence comparing tap and inject or early vitrectomy for treatment of IRE is inadequate to determine an optimal treatment strategy.ConclusionIntravitreal injections are sight saving, but even using established prophylactic measures there remains a small but real risk of infectious injection-related complications. Further investigations comparing tap and inject versus vitrectomy may help to establish optimal treatment, although the rarity of IRE makes designing adequately powered prospective trials a difficult task.

ENDOPHTHALMITIS AFTER INTRAVITREAL INJECTIONS DURING THE COVID-19 PANDEMIC WITH IMPLEMENTATION OF UNIVERSAL MASKING.

To evaluate the rates of postintravitreal injection-related endophthalmitis during the COVID-19 pandemic with institution of both physician and patient face masking. All eyes receiving intravitreal injections of any kind from a single large tertiary retina practice in Houston, TX before (August 2017-March 22, 2020) and after (March 23, 2020-September 2020) COVID-19 pandemic universal masking protocols. The total number of injections and cases of acute injection-related endophthalmitis were determined from billing records and subsequent retrospective chart review. The primary outcome was the rate of endophthalmitis after intravitreal injection. Secondary outcomes included visual acuity, time until initial presentation, patient age, and differences in the overall number of injections performed monthly pre-COVID-19 and post-COVID-19. A total of 134, 097 intravitreal injections were performed during the study period (111,679 pre-COVID-19 and 22,418 post-COVID-19 masking protocols). A total of 41 cases of acute endophthalmitis occurred in the pre-COVID group (0.04%, one in 2,500) and 7 cases in the post-COVID group (0.03%, one in 3,333) P = 0.85. In this single center, retrospective study, the implementation of universal patient and physician masking as practiced during the COVID-19 pandemic did not significantly affect the rate of postintravitreal injection endophthalmitis.

LONG-TERM VISUAL OUTCOMES AND CLINICAL FEATURES AFTER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTION-RELATED ENDOPHTHALMITIS.

To determine long-term visual outcomes in patients who developed endophthalmitis after intravitreal anti-vascular endothelial growth factor injections and to correlate visual outcomes with clinical features. This is a retrospective, multicenter, consecutive case series of patients diagnosed with anti-vascular endothelial growth factor injection-related endophthalmitis who were treated at Mid Atlantic Retina, the Retina Service of Wills Eye Hospital, Philadelphia, PA, and the University of Southern California Roski Eye Institute, Los Angeles, CA. Patients were included if they had at least 1 year of follow-up. Primary outcome was to evaluate long-term visual outcomes up to 5 years of follow-up. The secondary outcome was to determine clinical features (e.g., culture results) that may predict long-term visual acuity outcomes. A total of 56 cases of endophthalmitis from 168,247 anti-vascular endothelial growth factor injections were identified (0.033%, 1/3,004 injections), from which 51 eyes met inclusion criteria. Mean follow-up period was 3.3 years (median 4 years; range 1-5 years). A total of 24 patients (47%) reached a maximum final follow-up of 5 years. Mean Snellen visual acuity at the causative injection visit was 20/102 and decreased to counting fingers at diagnosis (P < 0.001). At 6-month follow-up, mean visual acuity improved to 20/644 (P < 0.001) and remained stable up to 5 years (20/480, P = 0.003) follow-up compared with diagnosis. At the final follow-up, 20 eyes had visual acuity that returned to within one line of baseline visual acuity (visual recovery group), whereas 31 patients' visual acuity was at least one line worse than initial visual acuity (visual deterioration group). The cultures for the visual recovery group were more likely to grow coagulase-negative Staphylococcus, whereas the visual deterioration group primarily grew Streptococcus species, Staphylococcus aureus, and Enterococcus faecalis (P = 0.002, comparing organisms isolated in the visual recovery and deterioration group). Visual outcomes after anti-vascular endothelial growth factor injection-related endophthalmitis seem to reach peak improvement by 6 months and remain stable up to a median of 4-year follow-up. Patients who develop culture-negative endophthalmitis or endophthalmitis secondary to coagulase-negative Staphylococcus are more likely to regain baseline visual acuity compared with cases secondary to Streptococcus species.

Lid splinting eyelid retraction technique: a minimised sterile approach for intravitreal injections

Background/aimsTo describe an alternative technique for avoiding contact with the lids and lashes, without the use of a lid speculum, during intravitreal anti-vascular endothelial growth factor injections.MethodsRetrospective case series of...

Endophthalmitis After Intravitreal Injections in Patients With Self-reported Iodine Allergy

To present cases of endophthalmitis following intravitreal injections where povidone-iodine (PI) was not used as part of the surgical preparation. Retrospective case series. All cases of presumed injection-related endophthalmitis presenting to the Massachusetts Eye and Ear Infirmary between June 2008 and November 2014 and Dean McGee Eye Institute between January 2010 and January 2015 were identified. Patients who did not receive PI preparation owing to documented self-reported allergy to iodine, iodine-containing contrast material, or shellfish were identified and their injection histories and clinical courses reviewed. The combined rate of postinjection endophthalmitis at these 2 centers was 0.019%. Among 42 patients with postinjection endophthalmitis, 5 (11.9%) did not receive PI prophylaxis. The mean number of intravitreal injections without PI before the development of endophthalmitis was 10.6 with a 9.4% rate of endophthalmitis (5 cases per 53 injections). All patients underwent tap-and-inject procedures with vancomycin 1mg and ceftazidime 2mg. Two patients did not receive PI at the time of tap and inject; 1 of these patients required subsequent pars plana vitrectomy for worsening clinical course. Cultures were positive in 4 of 5 cases; all positive cultures grew coagulase-negative Staphylococcus. All patients who received subsequent intravitreal injections received PI prophylaxis without allergic reactions, thus demonstrating a lack of true PI allergy. Avoiding PI owing to self-reported iodine "allergy" risks substantial ocular morbidity. Allergy testing can be pursued per patient request or in rare cases of suspected true PI allergy; however, in cases where delayed treatment would adversely affect visual outcome, the clinician should feel confident that minimal allergic risk exists.

Prevention and treatment of injection-related endophthalmitis.

Intravitreal injections are the fastest growing cause of endophthalmitis and can result in severe vision loss. The prevention, diagnosis and management of such infections remain unclear and at times controversial. We searched Pubmed for keywords "prophylaxis," "endophthalmitis," "intravitreal injection." We focused on studies published in the last 2 years as well as other recent studies with particular attention to data on the incidence, microbiology, prevention, and treatment of injection-related endophthalmitis. Over 20 relevant studies were found. With povidone-iodine preparation, the per-injection endophthalmitis rate is low at about 0.03%. Antibiotics do not appear to be beneficial for prevention of post-injection endophthalmitis. The best timing of vitrectomy is unclear. Antibiotic prophylaxis is probably not needed when giving intravitreal injections. More data is needed to help determine the proper treatment for post-injection endophthalmitis.

Acute Endophthalmitis After Intravitreal Injection and Preventive Effect of Preoperative Topical Antibiotics

To evaluate the incidence, causative organism, clinical features, and visual outcome of acute endophthalmitis following intravitreal injection and to report the clinical outcome of patients receiving preinjection antibiotics for the prevention of endophthalmitis. For all intravitreal triamcinolone acetonide, bevacizumab, ranibizumab, and C3F8 gas injections performed in our outpatient clinic between June 2008 and November 2012, the number of injections, indications, types of administered drugs, and methods of injection were investigated. A retrospective chart review was performed comparing patients with self-administration of antibiotic eye drops for 3 days before injection (n=8649 injections), and patients those who received no pretreatment with antibiotics (n=8683 injections). Cases of suspected endophthalmitis after intravitreal injection during this period were identified and reviewed retrospectively. The total number of intravitreal injections was 17,332. The incidence of acute endophthalmitis for all intravitreal injections was 0.000% (0/849) for triamcinolone acetonide, 0.022% (2/9,125) for bevacizumab, 0.000% (0/7,061) for ranibizumab, and 0.337% (1/297) for C3F8 gas injections. The overall rate of intravitreal injection-related endophthalmitis with the use of topical antibiotics given 3 days before injection was no less statistically significant compared with that of no antibiotics. Staphylococcus species was confirmed in the bacterial culture of one eye with acute endophthalmitis. After early vitrectomy and intravitreal antibiotic injection, one eye maintained vision, but the other eye developed phthisis. All 3 endophthalmitis patients had not taken prophylactic preinjection topical antibiotics, but the difference in the rates of endophthalmitis between those who received a multiday course of preinjection antibiotics and those who did not was not statistically significant. The rate of endophthalmitis after intravitreal injection using aseptic techniques in the clinical practice setting is similar with or without the use of preinjection antibiotics. Preinjection antibiotic use confers no additional benefit in the treatment of endophthalmitis compared to without preinjection antibiotics.

Incidence of Endophthalmitis and Use of Antibiotic Prophylaxis after Intravitreal Injections

To report the incidence of endophthalmitis in association with different antibiotic prophylaxis strategies after intravitreal injections of anti-vascular endothelial growth factors and triamcinolone acetonide. Retrospective, comparative case series. Fifteen thousand eight hundred ninety-five intravitreal injections (9453 ranibizumab, 5386 bevacizumab, 935 triamcinolone acetonide, 121 pegaptanib sodium) were reviewed for 2465 patients between January 5, 2005, and August 31, 2010. The number of injections was determined from billing code and patient records. The indications for injection included age-related macular degeneration, diabetic macular edema, central and branch retinal vein occlusion, and miscellaneous causes. Three strategies of topical antibiotic prophylaxis were used by the respective surgeons: (1) antibiotics given for 5 days after each injection, (2) antibiotics given immediately after each injection, and (3) no antibiotics given. The primary outcome measures were the incidence of culture-positive endophthalmitis and culture-negative cases of suspected endophthalmitis. Nine eyes of 9 patients with suspected endophthalmitis after injection were identified. Three of the 9 cases had culture-positive results. The overall incidence of endophthalmitis was 9 in 15 895. The incidence of culture-negative cases of suspected endophthalmitis and culture-proven endophthalmitis after injection was 6 in 15 895 and 3 in 15 895, respectively. Taking into account both culture-positive endophthalmitis and culture-negative cases of suspected endophthalmitis, the incidence per injection was 5 in 8259 for patients who were given antibiotics for 5 days after injection, 2 in 2370 for those who received antibiotics immediately after each injection, and 2 in 5266 who received no antibiotics. However, if considering culture-proven endophthalmitis alone, the use of topical antibiotics, given immediately or for 5 days after injection, showed lower rates of endophthalmitis compared with those without postinjection antibiotics. The risk of endophthalmitis after intravitreal injection varied among agents that were used. Among the 9 cases of clinically suspected endophthalmitis, regardless of prophylactic strategies used, the incidence of endophthalmitis per injection was 2 in 935 for triamcinolone acetonide, 3 in 9453 for ranibizumab, and 4 in 5386 for bevacizumab. The overall rate of intravitreal injection-related endophthalmitis is greater with the use of topical antibiotics, given immediately or for 5 days after the injection, compared with no antibiotics.

ENDOPHTHALMITIS AFTER INTRAVITREAL INJECTION

To determine the rate of postinjection endophthalmitis and compare microbial etiology and outcomes in office-based injection-related endophthalmitis versus those acquired after operating room procedures. Retrospective, observational case series. Consecutive cases of endophthalmitis seen at Retina Consultants of Houston between July 2000 and July 2010 were classified as postsurgical or post-intravitreal injection. Cases secondary to glaucoma surgery, trauma, and endogenous sources were excluded. Main study measures were incidence of endophthalmitis, microbiology results, and visual outcomes. In all, 109 cases of endophthalmitis were identified: 88 postsurgical and 21 post-intravitreal injection (3 from clinical trials and 5 from outside ophthalmologists). A total of 33,580 intravitreal injections were performed at Retina Consultants of Houston (endophthalmitis rate = 0.04%, 13 of 33,580; 95% confidence interval, 0.02-0.07%). The most common organisms isolated overall were coagulase-negative staphylococci, while viridans streptococci, a component of human oral flora, was identified over three times more often in the postinjection group compared with the postsurgical group. Compared with all other culture-positive cases related to intravitreal injection, postinjection endophthalmitis secondary to viridans streptococci presented much more rapidly (P < 0.001) and final visual outcomes were much worse (P = 0.004) Although the overall risk of postinjection endophthalmitis is low, viridans streptococci were identified over three times more frequently in postinjection cases compared with postsurgical cases and these cases had much worse clinical outcomes. The office-based setting for intravitreal injections may lead to a higher risk for infection from oral pathogens.

Expanded 2-Year Follow-up of Ranibizumab Plus Prompt or Deferred Laser or Triamcinolone Plus Prompt Laser for Diabetic Macular Edema

To report expanded 2-year follow-up of a previously reported randomized trial evaluating intravitreal 0.5 mg ranibizumab or 4 mg triamcinolone combined with focal/grid laser compared with focal/grid laser alone for treatment of diabetic macular edema (DME). Multicenter, randomized clinical trial. A total of 854 study eyes of 691 participants with visual acuity of 20/32 to 20/320 (approximate Snellen equivalent) and DME involving the fovea. Continuation of procedures previously reported for the randomized trial. Best-corrected visual acuity and safety at the 2-year visit. At the 2-year visit, compared with the sham + prompt laser group, the mean change in the visual acuity letter score from baseline was 3.7 letters greater in the ranibizumab + prompt laser group (95% confidence interval adjusted for multiple comparisons [aCI], -0.4 to +7.7), 5.8 letters greater in the ranibizumab + deferred laser group (95% aCI, +1.9 to +9.8), and 1.5 letters worse in the triamcinolone + prompt laser group (95% aCI, -5.5 to +2.4). After the 1- to 2-year visit in the ranibizumab + prompt or deferred laser groups, the median numbers of injections were 2 and 3 (potential maximum of 13), respectively. At the 2-year visit, the percentages of eyes with central subfield thickness ≥250 μm were 59% in the sham + prompt laser group, 43% in the ranibizumab + prompt laser group, 42% in the ranibizumab + deferred laser group, and 52% in the triamcinolone + prompt laser group. No systemic events attributable to study treatment were apparent. Three eyes in 3 (0.8%) of 375 participants had injection-related endophthalmitis in the ranibizumab groups, whereas elevated intraocular pressure and cataract surgery were more frequent in the triamcinolone + prompt laser group. The expanded 2-year results reported are similar to results published previously and reinforce the conclusions originally reported: Ranibizumab should be considered for patients with DME and characteristics similar to those of the cohort in this clinical trial, including vision impairment with DME involving the center of the macula.

Randomized Trial Evaluating Ranibizumab Plus Prompt or Deferred Laser or Triamcinolone Plus Prompt Laser for Diabetic Macular Edema

Evaluate intravitreal 0.5 mg ranibizumab or 4 mg triamcinolone combined with focal/grid laser compared with focal/grid laser alone for treatment of diabetic macular edema (DME). Multicenter, randomized clinical trial. A total of 854 study eyes of 691 participants with visual acuity (approximate Snellen equivalent) of 20/32 to 20/320 and DME involving the fovea. Eyes were randomized to sham injection + prompt laser (n=293), 0.5 mg ranibizumab + prompt laser (n=187), 0.5 mg ranibizumab + deferred (> or =24 weeks) laser (n=188), or 4 mg triamcinolone + prompt laser (n=186). Retreatment followed an algorithm facilitated by a web-based, real-time data-entry system. Best-corrected visual acuity and safety at 1 year. The 1-year mean change (+/-standard deviation) in the visual acuity letter score from baseline was significantly greater in the ranibizumab + prompt laser group (+9+/-11, P<0.001) and ranibizumab + deferred laser group (+9+/-12, P<0.001) but not in the triamcinolone + prompt laser group (+4+/-13, P=0.31) compared with the sham + prompt laser group (+3+/-13). Reduction in mean central subfield thickness in the triamcinolone + prompt laser group was similar to both ranibizumab groups and greater than in the sham + prompt laser group. In the subset of pseudophakic eyes at baseline (n=273), visual acuity improvement in the triamcinolone + prompt laser group appeared comparable to that in the ranibizumab groups. No systemic events attributable to study treatment were apparent. Three eyes (0.8%) had injection-related endophthalmitis in the ranibizumab groups, whereas elevated intraocular pressure and cataract surgery were more frequent in the triamcinolone + prompt laser group. Two-year visual acuity outcomes were similar to 1-year outcomes. Intravitreal ranibizumab with prompt or deferred laser is more effective through at least 1 year compared with prompt laser alone for the treatment of DME involving the central macula. Ranibizumab as applied in this study, although uncommonly associated with endophthalmitis, should be considered for patients with DME and characteristics similar to those in this clinical trial. In pseudophakic eyes, intravitreal triamcinolone + prompt laser seems more effective than laser alone but frequently increases the risk of intraocular pressure elevation.

Uveitis: Intravitreales Triamcinolon bei zystoidem Makulaödem

Cystoid macular edema (CME) is the most frequent cause of severe loss of visual acuity in uveitis. Among the systemic corticosteroids and immunosuppressive agents, the local use of intravitreal triamcinolone acetate (TA) is evaluated. Intravitreal injections of 10 mg TA were performed in ten eyes of six patients with persisting uveitic CME in spite of systemic cortisone or immunosuppressive therapy. The mean follow-up time was 9.8 months (range: 3-18). Visual acuity increased from 0.58 logMAR to 0.21 logMAR. In two eyes of one patient, repeated intravitreal injections of TA were necessary. Side effects included a increase of intraocular pressure (IOP) up to 25 mmHg or more in 30% of the eyes. In these three eyes, IOP was successfully controlled by local antiglaucomatous therapy (IOP < or = 20 mmHg). The dosage of systemic steroids had to be augmented in two eyes. In no patient was injection-related endophthalmitis, vitreous hemorrhage or retinal detachment observed. Intravitreal TA is an effective local therapy for CME due to uveitis without systemic side effects. It cannot replace the systemic basal therapy of uveitis, since the long-term effects are limited. It can be used as a bridging therapy until a systemic immunosuppression is started. It may, furthermore, be a therapeutic option when side effects of immunosuppressive agents are expected.