Associated with trauma
Endophthalmitis before primary repair
Endophthalmitis after primary repair
Pain out of proportion to the degree of trauma
Visual loss worse than media opacities suggest
Further reduction in visual acuity
Intraocular tissue prolapse
Purulent exudation from the wound
Corneal epithelial edema or erosion
Corneal ring infiltrate
Corneal ring infiltrate
No hypopyon (severe inflammation might be seen especially if the iris is involved)
No retinitis (retinal or subretinal hemorrhages might be present)
A 40-year-old male presented with typical infectious endophthalmitis 12 days after open-globe injury with a metal blade. Corneal perforation site had been sutured with 10/0 nylon on the day of trauma. Ocular pain started 7 days after the laceration. At the time of admission, eyelid edema, diffuse conjunctival hyperemia, severe anterior chamber inflammation, and hypopyon were present.
Clinical signs of infection include purulent discharge, edema of the eyelids, chemosis, corneal edema, hypopyon, and/or anterior chamber inflammation (pupillary membrane, posterior synechia), vitritis, and vitreous inflammation, and if the media opacity is mild to moderate, retinitis and periphlebitis can be seen (Cases 5.1 and 5.2a, d) [13, 19, 21, 22, 24].
A slowly progressing inflammation and vitreous pearls which are unresponsive to antibiotics should alert for fungal endophthalmitis (Fig. 5.1, Case 5.6) [2, 22]. In contrast to the intense pain in bacterial endophthalmitis, these patients have minimal discomfort. Clinicians should always consider endophthalmitis in eyes with a history of trauma regardless of the time of the injury since the onset of the symptoms might vary even after years from the trauma .
Vitreous pearls in a fungal endophthalmitis patient
A 38-year-old male was presented to our clinic with a 3-day-old trauma to the left eye. Visual acuity was hand motions. A self-sealing corneal perforation with negative Seidel test was seen. The typical picture of endophthalmitis was present (conjunctival hyperemia, severe anterior chamber inflammation, hypopyon, and vitritis) in addition to a ruptured lens capsule. Since we could schedule the surgery to the next day (which was the earliest possible time), we performed tap and inject procedure (intravitreal injection of vancomycin, ceftazidime, and dexamethasone) immediately (a). Computerized tomography of the patient showed intraocular metallic foreign body (b). B-scan ultrasound showed severe vitreous inflammation with attached retina and a hyperechoic foreign body with shadowing effect (c). Pars plana vitrectomy (PPV) was performed with lensectomy and IOFB removal on the next day (d). IOFB removal was done through anterior chamber. Mild retinitis and sub-ILM inflammatory debris were seen (e). Removal of ILM with the help of ILM-Blue was needed to clear the inflammatory debris (f). Fluid–air–silicone exchange was done at the end of surgery. There was no sign of endophthalmitis or inflammation 48 h after the surgery (g). Postoperative 1-month follow-up showed no sign of infection or inflammation, and best-corrected visual acuity was 0.6 with silicone oil in the eye (h).
Symptoms of extreme pain supported by hypopyon and vitritis should indicate endophthalmitis until proven otherwise. If the symptoms and signs are subtle, diagnosis can be difficult. An increase in pain, inflammation, and vitritis and decrease in vision should support endophthalmitis. Patient should be monitored closely (even hourly) until the signs and symptoms improve or worsen to have a definite diagnosis . If endophthalmitis is suspected, samples for cultures and stains should be obtained [16, 18, 22]. Cultures can be obtained from conjunctiva, wound, anterior chamber, or vitreous. Samples should be plated on blood and chocolate agar. Gram stain should also be performed [12, 16]. If fungal infection is suspected, Grocott’s silver stain, periodic acid–Schiff stain, culture on Sabouraud’s dextrose agar, or potassium hydroxide (KOH) preparation should be done [2, 25, 26]. Authors previously reported that DNA typing can rapidly and effectively detect fungal pathogens .
Pain from endophthalmitis might be differentiated from pain from trauma if the pain is disproportionate to the degree of injury. This may be an important clue before development of other typical signs of endophthalmitis like hypopyon.
If infection progresses despite treatment, panophthalmitis should be suspected if signs of orbital inflammation are apparent, such as limited range of ocular movement, proptosis, increased eyelid edema, and erythema. During the assessment of post-traumatic endophthalmitis, all eyes should be evaluated for IOFB [18, 28]. In most of the cases because of corneal edema, anterior chamber inflammation, cataract, vitritis, and vitreous hemorrhage IOFB visualization may not be possible. Plain radiography, B-scan ultrasonography, and computerized tomography (CT) should be used to detect IOFB. CT sections should be less than 2 mm apart in order not to miss a small IOFB (Case 5.2b, c).
5.4 Risk Factors
There are many risk factors that are associated with increased risk of endophthalmitis after open-globe injury:
The presence of IOFB
Delayed primary wound repair
Lens rupture and primary intraocular lens (IOL) implantation
Large wound size
Intraocular tissue prolapse
Age (>50 years old and pediatric age)
IOFB, as previously stated, increases the risk of post-traumatic endophthalmitis [10, 11, 13, 14, 29]. IOFB can affect visual prognosis in different ways: damaging the ocular structures physically (e.g., retinal tear), delivering the infectious organisms into the globe, and inducing damage with the chemical composition of IOFB (e.g., chalcosis, siderosis) . The composition of the IOFB is important as studies have shown that nonmetallic IOFBs may have a higher risk of endophthalmitis [11, 14, 28, 30]. Copper IOFBs should be removed as soon as possible because they can rapidly cause sterile inflammation with hypopyon and retinal detachment, mimicking endophthalmitis. Ionization of copper leads to changes in neurosensory retina and if left untreated causes visual loss within hours [28, 31]. IOFBs with iron content can cause siderosis. Free iron ions interact with epithelial cells and cause cell death with visual loss . Glass, plastic, and porcelain are inert materials which do not cause severe inflammation and are well tolerated in the eye . All IOFBs (inert or non-inert) increase the risk of endophthalmitis  and should be removed as soon as possible.
High-velocity particles, caused by blast explosions and combat injuries, should have a special consideration as they have a less risk of endophthalmitis. High velocity of the explosion may increase the temperature of the foreign body leading to self-sterilization. In these cases visual outcomes are associated with the structural damage caused by the IOFB rather than with the timing of removal [28, 34].
In case of IOFB, early vitrectomy with IOFB removal is important as vitrectomy removes the source of microorganisms (IOFB), pathogens, and nutrients (vitreous) .
5.4.2 Delayed Primary Wound Repair
Delayed primary wound repair is a risk factor for post-traumatic endophthalmitis. The risk is higher if time between the trauma and repair is more than 24 h [11, 14, 35]. There is a fourfold increase in the infection rate when there was a delay of more than 24 h (Case 5.3) .
A 35-year-old male with temporal corneal (zone I ) penetrating injury who presented to another hospital 4 days after trauma for primary repair was referred to us for endophthalmitis after primary repair. Visual acuity was hand motions with inflammatory fibrin membranes causing posterior synechia, hypopyon in the anterior chamber, and ruptured lens capsule. Retina could not be seen. An urgent vitrectomy was performed (a). Infusion was introduced through pars plana with anterior chamber maintainer being active during lensectomy. At this stage edematous corneal epithelium was scraped, and pupillary membranes together with lens particles were removed with vitrectomy probe (b). Visualization became better to see the severe vitreous inflammation (c). Following removal of vitreous membranes, retinitis and vasculitis signs were obvious (d). At this stage membranes at the ciliary body are seen and removed as much as possible with vitrectomy probe with the help of indentation (e). Surgery was completed with panretinal photocoagulation and silicone oil tamponade (f). Infection could be controlled and vision increased to counting finger (3 m) level, but significant hypotony developed despite of vigorous ciliary membrane removal during primary surgery. This hypotony led to migration of silicone oil into the anterior chamber, which had to be removed 2 months after the primary surgery. At the time of silicone oil removal, both vitreous cavity and anterior chamber were filled with an ophthalmic viscoelastic device, and pupilloplasty for temporal iris defect was also carried out (g). Postoperative fundus picture shows optic atrophy (h). Despite repeated injections of ophthalmic viscoelastic devices to anterior chamber and vitreous cavity 4–6 months apart, intraocular pressure was 2 mmHg.
5.4.3 Trauma in Rural Settings
Trauma in rural settings increases the risk of endophthalmitis after open-globe eye injury. In these settings trauma frequently occurs after farm-related accidents with contaminated objects [11, 15, 36]. It has been reported that injuries with contaminated objects increase the risk of endophthalmitis . The increased risk of endophthalmitis in open-globe injuries with organic matter may be because of increased microbial inoculum, more severe injury, and more resistant organisms . Most common trauma which causes IOFB-related endophthalmitis in a rural setting is hammering metal on metal . More than one organism is isolated in most of the endophthalmitis cases from rural areas. Bacillus species is the most common organisms in rural settings followed by Staphylococcus epidermidis and Gram-negative rods which will be discussed later . Soil-contaminated injuries carry a high risk of infection with Bacillus species and Clostridium species, both of which are highly virulent.
Virulence of microorganisms which are causing the infection should also be considered. This issue will be discussed in Sect. 5.7.
5.4.4 Lens Rupture and Primary IOL Implantation Are Considered as Risk Factors for Endophthalmitis After Open-Globe Injury Separately
Although there are studies that did not show lens rupture as a risk factor [11, 35, 37], many studies suggest that lens rupture is a risk factor for post-traumatic endophthalmitis [8, 10, 14]. In two different studies, endophthalmitis rates were shown to be 12.8 %  and 13.6 %  in eyes with lens rupture and only 3.2 % (n = 155)  and 0.9 %  in eyes with intact lens capsules. Thompson and colleagues hypothesized that lens rupture gives microorganisms direct access to vitreous cavity. The rupture of the lens capsule might also affect the aqueous humor dynamics and decrease the clearance of microorganisms from the anterior chamber . Ruptured lens may also serve as nutrient and medium for the growth of organisms [10, 14].
Primary IOL implantation may be assessed as another risk factor for endophthalmitis following open-globe injury [8, 38]. IOL implantation is considered when there is lens rupture and there is adequate visualization for IOL calculation. Andreoli and colleagues reported in their study with 675 open-globe injuries that primary IOL placement is a risk factor for post-traumatic endophthalmitis . In better words, it is not advised to implant an IOL during primary repair. It is safer to wait before implanting an IOL to allow the wound to heal and to allow the intraocular inflammation to subside. Additionally, during this period, clinician will be sure that there is no endophthalmitis following penetrating injury and a more accurate IOL measurement can be done after wound healing (Case 5.4).
A 12-year-old boy presented elsewhere for a corneal penetrating injury with a small metallic foreign body also penetrating the lens and stopping at the back of the eye. Primary corneal wound repair had been done together with primary cataract surgery with implantation of IOL within 24 h in elsewhere. He came back with the full-blown picture of endophthalmitis 3 days after and referred to us at this stage for vitrectomy combined with penetrating keratoplasty. Vision was light perception and the cornea was very cloudy with a central laceration area; there was hypopyon and inflammatory membranes covering and blocking the pupillary area (a). An urgent vitrectomy was performed. After debridement of corneal epithelium, aqueous sample was taken for microbiologic examination. Following removal of inflammatory membranes from the anterior chamber, IOL could be recognized which was seen to be an ACIOL. Following pars plana entry, vitreous sample was obtained, and membranes covering back of the lens in the pupillary area were also removed which made the view more clear (b) so that we could proceed with vitrectomy without penetrating keratoplasty. After removal of central vitreous opacities, we could reach to a small metallic foreign body within opacities. We extracted the ACIOL to make the view more clear and to take the IOFB out through the same limbal incision (c). The retina could be visualized nicely after these maneuvers, and 360° peripheral laser was applied. There were edema and scars in the macular area but retina was attached (d). The eye was left with silicone oil and 1/3 dose of intravitreal vancomycin and ceftazidime at the very end of the procedure. Culture was negative for the case, but infection could be controlled very well after the surgery with the given intravitreal antibiotics and topical moxifloxacin + dexamethasone every hour for the first 5 days which was tapered later. Silicone oil was removed 3 months after and the best-corrected visual acuity remained 20/400 at the last follow-up because of the macular scar. Patient was left aphakic.
5.4.5 Wound Size, Wound Site, and Wound Construction
Wound size, wound site, and wound construction are important for the visual prognosis and a risk factor for endophthalmitis. Lacerations (which are penetrating, perforating, or IOFB injuries) in general have a higher risk of endophthalmitis in open-globe injuries compared to ruptures . It has been shown that more than 8 mm in wound size is a risk factor for post-traumatic endophthalmitis . Although self-sealing of the wounds might be thought to be inferior to primary repair, it is shown to be equivalent to primary repair in protecting the integrity of wound construction .
Duch-Samper and colleagues reported in their retrospective study with 403 cases of penetrating eye injury that 2 % of corneal injuries developed endophthalmitis, whereas 7 % of posterior pole injures developed endophthalmitis (p = 0.03) . However in a more recent and larger study with 4968 eyes, Zhang and colleagues reported that 5 % of zone III injures had endophthalmitis in contrast to 14 % of zone I injuries (p < 0.001) . Zone III injuries might be protected against organisms by the overlying conjunctiva and Tenon’s capsule.
5.4.6 Intraocular Tissue Prolapse
Intraocular tissue prolapse might expose intraocular contents to exogenous flora and organisms and was traditionally thought to be a risk factor for endophthalmitis after open-globe injury . However Gupta  and Zhang  have reported that uveal or vitreous prolapse did not significantly increase the risk of endophthalmitis. Tissue prolapse may prevent invasion of exogenous organisms by plugging the wound, as well as it may facilitate invasion of exogenous organisms by forming a bridge through the wound. Further studies should be done to elucidate this issue.
During primary wound repair, prolapsed retina should never be excised. Prolapsed vitreous should be cut with sharp scissors, but excision of uveal tissue is not usually recommended because of the risk of significant hemorrhage . Before removing the prolapsed uveal tissue, timing of the repair and wound hygiene should also be considered. While repairing a laceration with uveal tissue prolapse more than 24 h after the injury, the highly necrotic uveal tissue should be excised . We also recommend removing the exposed prolapsed uveal tissue if the injury is of rural origin and there is significant debris on the surface of the exposed prolapsed tissue beyond the surgeon’s ability to clean.
Age was not shown to be an independent risk factor in multivariate analysis of the data for endophthalmitis after open-globe injury [14, 35]. However in two separate studies, Narang and Dehghani showed that low age (<15 years old) of the patients is associated with higher rate of endophthalmitis [42, 43]. Also Thompson and colleagues found from the 492 eyes with IOFB in the National Eye Trauma System Registry that post-traumatic endophthalmitis risk is increasing with age, especially in patients 50 years of age or older with delayed repair (p = 0.005) . We believe that children are at a higher risk for post-traumatic endophthalmitis development because of their low cooperation to examination which might delay the discovery of signs of endophthalmitis in coordination with their inability to tell the symptoms to their family which might delay the presentation to a clinician. We have three preverbal children who had accidental, self inflicted eye injury with injector needle, which was not noticed by the family and presented only after development of the signs of endophthalmitis. Since primary wound repair is delayed, it is not surprising that risk of endophthalmitis increases in these cases. Detailed information about pediatric post-traumatic endophthalmitis is discussed in Sect. 5.6.
5.4.8 Male Gender
Male gender to female ratio is reported up to 5.72:1  which might be related to the gender ratio in open-globe injuries (up to 5.1:1 ). Zhang and colleagues found in univariate analysis that gender was not a significant factor associated with the development of endophthalmitis (p = 0.63) . Results of Essex and colleagues were similar and found that gender was not associated with post-traumatic endophthalmitis .
5.5 Pediatric Post-traumatic Endophthalmitis
Children tend to have a high rate of endophthalmitis after open-globe injuries (from 3.1  to 54.2 % ). Clinical signs of endophthalmitis are similar to the ones in adults. However symptoms of post-traumatic endophthalmitis in children might be misleading. Depending on the age of the child, change in visual acuity and pain might be recognized late, and even if the symptoms are recognized early, the child might not bring them to the attention of an adult. This behavior may result in delayed recognition and delayed treatment of post-traumatic endophthalmitis in children (Cases 5.4 and 5.5) .
An 11-year-old boy has presented to another clinic with a 2-day history of pencil-tip injury of the left eye. He mentioned about the injury 2 days after the trauma to his parents. When they arrived to the hospital, intravitreal cefazolin and gentamicin had been administered with a diagnosis of endophthalmitis. After 3 days of follow-up, hypopyon was still apparent and the patient was referred to us. It has been 5 days after the injury then. Visual acuity was hand motion. There was lead mark in the corneal entry site, corneal edema, and hypopyon (a). B-scan ultrasound showed some vitreous opacities (b). Urgent vitreous tap and intravitreal injection (vancomycin, ceftazidime, and dexamethasone) were performed. Samples were obtained from the vitreous as well as anterior chamber. Postoperative infection was controlled, but visual acuity remained hand motion because of the lens and vitreous opacities (c). One week after admission, a pars plana vitrectomy and lensectomy were performed. During lensectomy posterior lens capsule was defective, and inflammatory material was observed inside the lens capsule. Pars plana lensectomy was performed together with a complete vitrectomy. Posterior hyaloid was not removed because of its strong adhesions to the posterior pole. There was no retinitis. The case ended up with a fluid–air exchange. Two weeks postoperatively, there were no signs of infection (d, e). Visual acuity was 0.2 with a refraction of +13 D.
Causative agents of post-traumatic endophthalmitis in children are different than adults. In children Streptococcus species is the most common agent (25–55 %), followed by Staphylococcus (18 %) and Bacillus species (22 %) . In adults it has been shown that Staphylococcus epidermidis and Bacillus are the most common organisms responsible for post-traumatic endophthalmitis [8, 21]. Fungal infection might also occur after organic matter injury .
Similar to post-traumatic endophthalmitis in adults, studies show that the presence of IOFB, rural setting, delayed primary repair of the injury (>24 h), injury with organic matter-contaminated objects, and involvement of lens capsule are risk factors [43, 47–50]. The rate of endophthalmitis in our pediatric trauma series was 12.1 % (22 of 182 eyes), most of them having late primary repair of the wound. Nineteen of them had vitrectomy, but only 15 % (three eyes) had a final VA of 20/200 or more .
A subset of pediatric patients who are 10 years or younger usually have a poor final visual acuity. Amblyopia plays an important role in this age group [21, 46]. However Narang and colleagues have showed that delayed primary repair is the major factor affecting visual prognosis .
Prognosis of pediatric post-traumatic endophthalmitis is usually guarded both because of delayed recognition and treatment and amblyopia development.
Several organisms have been reported as causative agents in post-traumatic endophthalmitis (Table 5.2). It is important to keep in mind that without clinical signs of infection, positive culture results do not mean that endophthalmitis will develop . Approximately 75 % of all post-traumatic culture-positive endophthalmitis cases are infected by Gram-positive organisms . The most common organisms among Gram-positive species are Staphylococcus epidermidis and Streptococcus species which are part of the normal skin flora and thus contaminate open wounds regularly . Post-traumatic endophthalmitis by Staphylococcus species tends to have a more favorable outcome compared to other organisms . Intravitreal vancomycin and ceftazidime are treatment of choice in Staphylococcus and Streptococcus species . Fourth-generation fluoroquinolones have excellent systemic penetration, and the MIC 90 for Staphylococcus and Streptococcus can be achieved with oral doses [55–57].
Fungi (8.3 %)
Gram positive (75 %)
Bacillus spp. (20 %)
Gram negative (10 %)
Mixed infections (15.6 %)
When there is an IOFB or a penetrating trauma with soil contamination, the risk of Bacillus species endophthalmitis is higher (20 %) . Bacillus species differs from other organisms in the onset and severity of the endophthalmitis they cause. Bacillus species endophthalmitis has a rapid onset (24 h) of severe pain and inflammation, chemosis, hypopyon, ring-shaped corneal infiltrate, and rapid progression to panophthalmitis. Its severity is likely caused by an enterotoxin-mediated reaction. Bacillus cereus infections tend to have a very high risk of causing no light perception . Intravitreal vancomycin and intravenous vancomycin have a good coverage against Bacillus species. In severe cases amikacin can be added intravitreally. Fluoroquinolones also have a good coverage and can be added as an oral treatment [8, 20, 60].
Clostridium genus is a group of anaerobic spore-forming bacilli that are Gram positive . Clinical signs of endophthalmitis associated with this pathogen include gas bubbles in the anterior chamber, amaurosis, and greenish-brown hypopyon [62, 63]. This organism is highly virulent and can cause endophthalmitis within 24 h with rapid progression and causing panophthalmitis [8, 63]. Visual outcome in most cases of Clostridium endophthalmitis is very poor generally resulting in no light perception [8, 61, 63]. Intravitreal vancomycin and ceftazidime can be used to treat Clostridium endophthalmitis following open-globe injury .
Gram-negative organisms are the cause of post-traumatic endophthalmitis less than Gram-positive organisms. They are reported to be the causative agent from 0 to 33 % of cases with post-traumatic endophthalmitis [52, 65, 66]. Although they are a rare cause of post-traumatic endophthalmitis, they are usually virulent, and the prognosis is poor. Pseudomonas is the most commonly isolated organism in this group. It has multiple drug resistance, and it is recommended to treat Pseudomonas with combination therapy. Tobramycin–piperacillin and tobramycin–ceftazidime are popular combinations. Fluoroquinolones also cover Pseudomonas, and ciprofloxacin, which is a third-generation fluoroquinolone, has the best coverage. Organisms that can cause fulminant endophthalmitis include Bacillus, Pseudomonas, and Clostridium species .
Polymicrobial infection is more frequent in endophthalmitis following open-globe injuries compared to other types of endophthalmitis (15.6 % ).
Fungi are less common than bacteria in post-traumatic endophthalmitis. The incidence of fungal agents is reported to be between 0 and 15.4 % [13, 26, 68]. The most common fungus causing post-traumatic endophthalmitis is Candida , but molds such as Aspergillus species, Paecilomyces species, Fusarium species, and dematacious fungi have also been reported [20, 69].
Differentiating between fungus and bacteria is important as their treatments are different. Late onset (1–5 weeks) of symptoms with a fairly asymptomatic external eye exam, slowly progressive intraocular inflammation, and/or the presence of vitreous inflammation (vitreous snow balls/vitreous pearls) might be suggestive of fungal infection [2, 70, 71] (Fig. 5.1, Case 5.6).
A 36-year-old female patient has been referred to our clinic with a history of a traffic accident with penetrating eye injury 3 months ago. From the previous reports, we learned that phacoemulsification with intraocular lens implantation was performed after primary wound repair in another clinic. Three separate pars plana vitrectomy surgeries with silicone oil had been done after intravitreal antibiotic injections were assessed insufficient. IOL was removed at the latest surgery. Only the first culture yielded Streptococcus species. Three of the later cultures revealed no organisms. Cultures for fungi had not been performed. Upon admittance to our clinic, there was central keratitis, severe anterior chamber inflammation. We got samples from the anterior chamber and cornea for fungi as soon as we admitted the patient. Cultures yielded Aspergillus terreus with a susceptibility to amphotericin B and voriconazole. Although we have started empirically, intravitreal and intracameral voriconazole treatment phthisis bulbi was inevitable. This case demonstrates the importance of differentiating fungal endophthalmitis and its severe complications if diagnosed late.
Visual prognosis in eyes with endophthalmitis secondary to trauma is poor. The visual prognosis is affected by the endophthalmitis as well as trauma itself [14, 35]. The effect of endophthalmitis on visual prognosis in an open-globe injury is described in the ocular trauma score (OTS) which can provide a probability estimate of the visual outcome 6 months after the injury [8, 72]. OTS calculates the probability considering many variables. Patients presenting visual acuity, the presence of rupture, perforating injury, retinal detachment, and afferent pupillary defect are factors effecting final visual outcome .