**4.1 Ocular risk factors**


## **4.2 Systemic risk factors**


Blebs located inferiorly are at increased risk of infection since there is greater exposure of the bleb to the tear lake with concentrated bacteria, less protection from the upper lid and more mechanical irritation from greater exposure [18]. The risk of infection in an inferiorly located bleb is x4–x 8 higher in eyes treated with antimetabolites [19].

Fornix-based conjunctival flap trabeculectomies are associated with reduced risk of BRI compared to limbal based conjunctival flap peritomy (hazard ratio 3.39) [20]. In one study, the incidence of late-onset BRI decreased from 5.7% to 1.2% following a change from limbal based to fornix based peritomy [21].

The use of antimetabolite agents, e.g., 5-Fluorouracil (5-FU) and Mitomycin C (MMC) has led to an increase in cases of BRI. The incidence before the use of antimetabolites was 0.2–1.5% [22–24]. This has increased to 2–13.0% in 5-FU treated eyes [25–27] and 1.5%–14% of MMC treated eyes [28–31].

Thin, cystic blebs associated with MMC, and 5-FU use are more prone to infection than blebs with a thick wall [32–35]. They are also associated with late bleb leak (leakage after 4 weeks), another risk factor for BRI [36–38].

In one study, the rate of BRI was 7.9% and 1.7% for blebs with and without leakage, respectively (202). The presence of bleb leak was associated with a 4.7-fold increase in the risk of BRI [38]. Bleb leak must therefore be addressed in an urgent manner by the glaucoma team.

Blepharoconjunctivitis is associated with microbial colonisation of the ocular surface, which is a risk factor for BRI [39–43].

An important practice pearl is to examine the ocular adnexa pre-operatively and to prepare the ocular surface in case of pre-existing blepharoconjunctivitis or nasolacrimal duct obstruction. Furthermore, post-operatively, all patients with an active bleb should be examined for blepharitis.

In patients with a filtering bleb and blepharoconjunctivitis, a short course of topical antibiotic (e.g., fucithalmic, tobramycin, bacitracin, or erythromycin) plus eyelid hygiene is recommended with prompt discontinuation of antibiotic upon resolution. However, the eyelid hygiene must be continued indefinitely. Rosacea blepharitis responds well to topical azithromycin or oral doxycycline [44]. For chronic blepharitis, 0.01% hypochlorous acid, which is a natural product, is an antimicrobial agent that can be used repetitively and long-term without resistance developing [45].

Aphakia and pseudophakia are associated with higher odds of BRI (6.3 v 2.85) [46]. Absence of an intact posterior capsule may enhance microbial penetration into the vitreous cavity [47].

A slightly lower rate of BRI was found in cases of combined trabeculectomy+ cataract surgery (1.4%) compared to trabeculectomy alone (1.5%) at 2.5 years

post-operatively. The lower rate of thin-walled blebs after a combined operation could explain this observation [39].

Diabetes mellitus (DM) is associated with higher positive conjunctival culture rate than in patients without DM. The severity of diabetic retinopathy is correlated to culture positivity (98). In some studies, 18% of cases of BRI had DM [29, 35, 37, 40–42, 48].

Younger age was found to be a risk factor for infection [49, 50], and severe bleb leak was associated with younger adults (<55 years) (99). In some studies, a high rate of BRI was found in children [51] including 8% chance of late onset endophthalmitis [52].

The association with gender is not clearly proven. Seasonal variation in temperature and humidity may influence the conjunctival flora and therefore, the rate of BRI [53].
