ENDOPHTHALMITIS

Endophthalmitis is an uncommon but devastating consequence of open globe injury.1 The relatively poor visual prognosis of traumatic endophtalmitis is due to:

•the higher frequency of organisms that are more virulent than those in postoperative cases;

•the associated trauma;

•the frequent delay in diagnosis; and

•the frequent delay in the initiation of treatment.2–13

Traumatic endophthalmitis therefore presents difficult diagnostic and management issues distinct from endophthalmitis occurring in other settings.

EPIDEMIOLOGY

The incidence of endophthalmitis after open globe injury is 5 to 14%;1,9,12,13 In the USEIR, the incidence is 2.6%.

Traumatic endophthalmitis constitutes approximately 10 to 30% of all infectious endophthalmitisa,4–8,12 cases. It is more common in males (85%).10 In the USEIR, the rate is 2.8% among males and 1.4% among females.

Risk factors for the development of traumatic endophthalmitis include:

•7 24 hours of delay in primary wound closure;

•presence of an IOFB (6.9–13%, independent of IOFB type)14;

a Postoperative, endogenous, traumatic, and filtering blebassociated.

•rural setting:

soil contamination is believed to result in a higher rate of endophthalmitis (30%) for open globe injuries occurring in a rural versus a nonrural setting11; and

•rupture of the lens capsule.13

CLINICAL DIAGNOSIS

The symptoms and signs are similar to those in other categories of endophthalmitis, but the diagnosis is often delayed due to masquerading signs that usually accompany severe ocular trauma. Early symptoms may include:

•photophobia;

•pain out of proportion to the clinical findings;

•visual loss worse than media opacities might suggest;

•hypopyon (Fig. 28–1);

•vitritis; and

•retinal periphlebitis.15

Other, less specific signs include:

•lid edema;

•conjunctival erythema and edema;

•corneal edema;

•fibrinous membrane formation on the iris, lens, or the IOL; and

•loss of the red reflex or progressively worsening view of the posterior pole.

FIGURE 28–1 One day after repair of a corneal laceration, this patient developed increasing pain and hypopyon. Vitrectomy specimen revealed Streptococcus faecalis.

Fungal infection is more common in the following injuries:

•IOFB, especially if it is vegetable matter (e.g., thorn, wood); or

•soil contamination.

Characteristic signs of intraocular fungal infection include:

•slowly progressive inflammation after initial trauma repair;

•white “snowball-like” opacities or “string-of- pearls” configuration in the vitreous;

•chronic vitritis; and

•persistent white infiltrates around the primary wound side.16

PEARL... Retinal periphlebitis is an early sign of endophthalmitis. However, it is often not recognized because of the common

presence of media opacities.

MICROBIOLOGY

The microbiology of traumatic endophthalmitis is significantly different from that in other categories. Infections with more than one organism are common (up to 48%).10,14 The organism is often virulent.

Gram-positive bacteria (usually cocci such as Streptococcus and Staphylococcus species) are the predomi-

nant isolates in both the adult and pediatric age groups.8,10–12 There is a high incidence of Bacillus species. These infections are notable for their:

•rapid (6 24 hours) onset;

•high risk of progression to panophthalmitis; and

•rate of poor visual outcome.

Endophthalmitis caused by Bacillus species is characterized by:

•severe pain;

•hypopyon;

•chemosis; and

•rapidly progressive proptosis and lid edema.

Additional information regarding Bacillus endophthalmitis includes the following.

•The characteristic ring-shaped corneal infiltrate is a late sign.

•Although rare in postoperative cases, it is rather common (up to 46% after open globe trauma) in the United States,11 representing the second most common group after Staphylococcus species in IOFB injuries.14

•Although it was previously considered to have a uniformly poor visual prognosis, early recognition and prompt treatment of infection caused by Bacillus species (Fig. 28–2) may occasionally result in good visual outcome.17,18

Culturing for Microbiologic Analysis

The first question is: in which cases should a sample be taken?

PEARL... When traumatic endophthalmitis is suspected, one should attempt

to culture intraocular contents in all cases.

C O N T R O V E R S Y

Following an open globe injury, the ophthalmologist may consider routinely culturing all cases, but such an approach will yield a fair number of false-positive results and probably adds little to the clinical care of the patient (see Chapter 24).

The second question is: where should the sample be taken from?

•We do not routinely culture the wound or conjunctiva: the high risk of contamination makes a positive culture difficult to interpret.

•We do culture the wound if there is a specific indication of infection present.

In reported series of traumatic endophthalmitis, vitreous specimens have a higher rate of positive culture than aqueous samples.19,20 The extent of vitrectomy performed to obtain samples depends on the visibility of the posterior segment and the surgeon’s experience (see the Appendix for more details).

The third question is: which culture media should be used? Commonly used plates for bacterial and fungal cultures are:

•blood agar; and

•chocolate agar.

With a larger intraocular specimen, smears can be sent for:

•Gram, Giemsa, and fungal stains;

•Sabouraud’s media (fungi);

•thioglycollate broth (all-purpose holding media); and

•anaerobic blood culture bottle.

Because the initial surgery is often performed in “off-hours,” the standard culture media may not be immediately available (see also the Appendix).

PEARL... After hours or on the weekends, when the microbiology personnel may not be available to process the vitreous specimen, the vitreous aspirate can be directly injected into blood culture bottles. The culture yield of this technique appears to be comparable to that of conventional methods21,22

(see also the Appendix).

Fungal cultures are indicated in cases in which initial bacterial cultures were negative or when fungal infection is strongly suspected.

PREVENTION:

PROPHYLACTIC ANTIBIOTICS

Systemic antibiotics, although not confirmed in a randomized prospective study, may reduce the incidence of endophthalmitis in eyes with open globe injury. The selected antibiotic should:

•provide coverage against the most common pathogens known to cause traumatic endophthalmitis (i.e., Bacillus species and gram-positive organisms); and

•have adequate intraocular penetration after systemic administration.

The ideal antibiotic regimen remains controversial; Table 28–1 shows one protocol for prophylaxis of traumatic endophthalmitis.

Topical therapy (started on the first postoperative day)

Antibiotic (physician’s choice, commercially available antibiotic in nonfortified concentration)

Topical cycloplegics and corticosteroids

Optional: fortified antibiotic drops may be substituted in high-risk injuries with suspicion of infection

•Although a first-generation cephalosporin may provide coverage for gram-positive organisms,23 intravenous vancomycin is an excellent choice because it:

is effective against Bacillus, Streptococcus, and

Staphylococcus species; and

has good intravitreal penetration.24–27

•Intravenous ampicillin/sulbactamb is an alternative systemic antibiotic with good intraocular penetration and generally good gram-positive coverage with variable coverage of Bacillus species.

•Intravenous ceftazidime provides good gramnegative coverage28,29 but is less effective than vancomycin in the coverage of Bacillus species. Ceftazidime has a good safety profile30 and good intravitreal penetration.31,32

•Oral ciprofloxacin has good intravitreal penetration.33

Systemic aminoglycosides are considered to have suboptimal intravitreal penetration.34,35

C O N T R O V E R S Y

The ideal antibiotic regimen for the prophylaxis of traumatic endophthalmitis remains controversial. The selected antibiotic should have adequate intraocular penetration after systemic administration and provide coverage against the most common causative organisms.

b Unasyn; Pfizer, New York, NY.

In addition to systemic antibiotics the following routes of administration may be considered.

•Subconjunctival and topical antibiotics are generally used and a postoperative cycloplegic such as scopolamine 0.25% is added.

•Intravitreal injection of antibiotics and dexamethasone in cases suspected to be at high risk for infection36 (see Table 28–2) can also be considered during the initial repair.

Antifungal prophylaxis for open globe repairs is generally not recommended in the absence of clinical and microbiologic evidence for fungal infection.16

Alternative (Outpatient) Approach to Prophylaxis

Intravenous antibiotics often require hospitalization for administration, and many physicians admit patients with open globe injuries to the inpatient unit for 48 to 120 hours. This treatment can be expensive and disruptive to the patients’ life and may be unnecessary. Alternatively, given the relatively high rates of infection following open globe injuries, most physicians would consider it to be “standard care” for these patients to receive some form of antibiotic prophylaxis.

Given the poor penetration into the posterior segment of most topical, subconjunctival, and orally administered antibiotics, these routes are probably not adequate for prophylaxis. As an alternative, one can consider intravitreal antibiotic administration at the time of wound repair. Intravitreal ceftazidime (2 mg 0.1 mL) and vancomycin (1 mg 0.1 mL) carry very low risk of intraocular toxicity and can be safely administered after the eye has been closed. In the setting of open globe injury, one should confirm ophthalmoscopically or with intraoperative ultrasound

Systemic antibiotic therapy

Intravitreal antibiotic and corticosteroid therapy

Subconjunctival antibiotic and corticosteroid therapy

Topical therapy (started on first postoperative day)

Vancomycin hydrochloride, 1 g iv every 12 h Ceftazidime, 1 g iv every 12 h

Vancomycin hydrochloride, 1 mg 0.1 mL Ceftazidime, 2 mg 0.1 mL *Dexamethasone, 0.4 mg 0.1 mL

Vancomycin hydrochloride, 25 mg

Ceftazidime, 100 mg

Dexamethasone, 12 mg

Vancomycin hydrochloride, 50 mg mL every hour Ceftazidime, 50 mg mL every hour or

gentamicin sulfate, 14 mg mL every hour Topical cycloplegics and corticosteroids

that large choroidal detachments or retinal detachment is not present, which might complicate the pars plana injection of these antibiotics (see the Appendix).

S P E C I A L C O N S I D E R A T I O N

In selected cases of open globe injury suspected to be at high risk for developing endophthalmitis or to allow outpatient management of the open globe injury, intravitreal injection of antibiotics can be considered immediately following the primary repair.

C O N T R O V E R S Y

Routine administration of prophylactic antibiotics into the vitreous is not universally accepted; it may theoretically increase the rate/speed of development of drug resistance.

TREATMENT

Bacterial Infection

Vitrectomyc

Early vitrectomy is recommended in most cases of clinically suspected traumatic endophthalmitis. The progression of traumatic endophthalmitis can be very

c May be combined with TKP (see Chapter 25).

rapid because of the more virulent organisms and the often large infectious inoculum in the eye.

Vitrectomy is theoretically beneficial by:

•debulking inflammatory debris and toxins;

•removing the scaffold for tractional preretinal membranes; and

•allowing better distribution of intraocular antibiotics.

P I T F A L L

The results of the EVS are probably not applicable to cases of traumatic endophthalmitis as the organisms, the age of the patient, and the mechanism of inoculation are different.

C O N T R O V E R S Y

Recently, there have been successful reports of using silicone oil at the completion of vitrectomy, reducing the postoperative complications without causing recurrence of the infection or concentrating the infecting organisms in the vicinity of the inferior retina. The eyes are irrigated with a solution containing antibiotics during vitrectomy, but no antibiotics are left/injected in the vitreous once the silicone oil has been implanted.

Performing a more complete vitrectomy (as opposed to the traditional core vitrectomy), consistent with safe intraoperative visualization (proportional pars plana vitrectomyd), may increase the success rate in restoring/salvaging macular function.37

Antibiotics

Intravitreal, periocular, topical, and systemic antibiotics are recommended. The current treatment of clinically diagnosed traumatic endophthalmitis is outlined in Table 28–2 (see also the Appendix regarding intravitreal antibiotics). As an alternative to ceftazidime, amikacin or gentamicin can be considered in the subconjunctival regimen. Fortified topical antibiotics are started on the first postoperative day. In eyes with early endophthalmitis with clinical improvement and susceptible organisms, the regimen may be switched to an oral systemic agent.33,38 Animal studies of Bacillus cereus traumatic endophthalmitis have suggested that intravitreal imipenem may be as effective as vancomycin in these infections.39

Corticosteroids

Even if somewhat controversial,40 adjunctive intravitreal corticosteroids (dexamethasone, 0.4 mg in 0.1 mL) have been successfully used in traumatic endophthalmitis.41 Subconjunctival dexamethasone (12 to 24 mg) is also routinely given at the time of vitrectomy. Topical steroid drops (prednisone acetate 1%) are started on the first postoperative day.

Fungal Infection

To avoid the potential posterior segment toxicity of intravitreal amphotericin B,42 it is generally reserved for secondary treatment based on the clinical history, initial clinical signs, or documented fungal cultures. Traumatic fungal endophthalmitis may be caused by yeasts (e.g., Candida species) or by filamentous fungi (e.g., Aspergillus species), which are usually sensitive to intravitreal amphotericin B (0.005 mg in 0.1 mL).

Intravenous amphotericin B may cause significant systemic side effects. Its use generally requires prolonged hospitalization, renal function monitoring, and the use of antipyretics and fluid replacement for spiking fevers, nausea, and vomiting with dehydration.

PEARL... Systemic antifungal therapy is best selected and administered in consultation with an internist (e.g., oral flucona-

zole vs. intravenous amphotericin B).

Occasionally, fungal endophthalmitis is caused by an organism resistant to amphotericin B (e.g., Paecilomyces lilacinious16), requiring alternative intravitreal and systemic agents.

Intravitreal,41,43 subconjunctival, and topical corticosteroids can also be considered in traumatic fungal endophthalmitis.

SPECIAL ISSUES

Persistent Endophthalmitis after Initial Treatment

Most cases of traumatic endophthalmitis are successfully managed with vitrectomy and intravitreal antibiotics. However, in the presence of persistent/ worsening inflammation with a particularly virulent organism (e.g., Bacillus species), repeated vitrectomy and intravitreal injections can be considered.

•In one study of culture-proven endophthalmitis of various types, a second vitreous culture and antibiotic injection was needed in 52% of eyes,44 performed 3–8 days after the initial treatment; 29% of eyes were still culture positive. Eyes in which the initial antimicrobial therapy failed to eradicate a bacterial infection had a worse outcome than those that were culture negative on repeated sampling.

•In the EVS,45 7.5% of patients underwent reinjection of intravitreal antibiotics within 7 days of initial treatment because of persistent or worsening inflammation/infection. These patients, along with others who had additional procedures within 7 days of the initial treatment, demonstrated substantially worse visual outcomes compared with patients who required no additional procedures.

S P E C I A L C O N S I D E R A T I O N

In cases of persistent post-traumatic endophthalmitis, repeated intravitreal antibiotic injection can be safely performed 48 to 72 hours after the initial treatment, althoughe it may enhance the risk of retinal toxicity.46–50

Concurrent Retinal Detachment

Concurrent presence of retinal detachment and endophthalmitis poses a management challenge in eyes with open globe injury. Improvements in early diagnosis and treatment of endophthalmitis, along with advances in vitreoretinal surgical techniques, have nevertheless

made it possible to achieve a favorable outcome in some cases.51,52 Potential approaches include the following.

•The retinal detachment is repaired by pars plana vitrectomy, possible scleral buckling, fluid–air exchange, and endolaser. The air can then be exchanged for a

long-acting gas such as C3F8. After the vitreous cavity is 50% refilled with BSS, the desired intravitreal antibiotics are injected.

•Use of antibiotics in the irrigating fluid or use of a 50% dosage into the partially gas-filled eye.

•Silicone oil use (see earlier).

The visual prognosis is often correlated with the virulence of the causative organism.50

•In cases requiring a more complete gas fill (inferior retinal breaks), the surgeon can inject the intravitreal antibiotics prior to the fluid–air exchange and allow adequate time (10 minutes) for the diffusion

REFERENCES

CHAPTER 28 ENDOPHTHALMITIS • 299

of the antibiotics throughout the vitreous cavity. This will reduce the chance of overconcentrating the antibiotics when only a small amount of fluid is left in the cavity.

SUMMARY

Endophthalmitis associated with open globe injuries presents a formidable clinical challenge in both diagnosis and management. Early recognition of clinical signs and prompt initiation of treatment will improve the otherwise poor visual prognosis. Even in eyes with highrisk features, such as infection with Bacillus species or concurrent retinal detachment, successful anatomic and useful visual acuity outcomes can be achieved. Vitrectomy should be considered in all, and performed in the vast majority of, eyes; intravitreal antibiotics (and probably corticosteroids) must also be used.

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