Ординатура / Офтальмология / Английские материалы / Retinal and Vitreoretinal Diseases and Surgery_Boyd, Cortez, Sabates_2010

Hypopyon may be seen as the initial manifestation in such cases. Fibrin, a strong indicator of infection is usually mild or absent in sterile endophthalmitis. It manifests very early on in the postoperative course, usually within the first 24 to 36 hours. On the whole, the clinical picture is much less severe, with mild diminution of the fundal glow, mild vitreous haze, absence of focal infiltrates or nidus of infection. Use of ultrasound can describe and pin-point an inflammatory process affecting only the anterior segment of the eye versus a vitreous reaction, increasing vitreous opacities, or retinal or choroidal detachment or thickening.

The increasing popularity of triamcinolone injections for many disease entities associated with macular edema has led to recent reports of the complications associated with this treatment. Intraocular pressure elevation and endophthalmitis are recognized complications of Intravitreal triamcinolone injections. Although some patients appear to have an infectious endophthalmitis, many of the reports detail a “presumed noninfectious endophthalmitis” or “pseudoendophthalmitis”thatresolveswithout invasive treatment that necessitate proper

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informed consent from patients undergoing this procedure.

However, it is of utmost importance that all unexpected postoperative reactions of the eye should be considered as infective, unless proven otherwise.

Diagnosis

The ophthalmologist must maintain a high index of suspicion for endophthalmitis in patients with persistent or increasing intraocular inflammation above the expected level because definitive management of postoperative endophthalmitis begins with the correct diagnosis, and early treatment is critical in achieving a good outcome. Although clinical findings may be highly suggestive, the diagnosis should be secured and antibiotic therapy guided by anterior chamber and vitreous taps for culture (Figures 1 and 2). An anterior tap by itself is not sufficient because in up to 40% of cases in which the vitreous tap is positive, the anterior chamber tap is negative. The vitreous tap should be obtained before antibiotics are administered.

Endophthalmitis After

Penetrating Trauma

Patients with penetrating ocular trauma are at risk of developing endophthalmitis and are usually treated with broad-spectrum intravenous antibiotics for several days. If possible, a sample of the intraocular fluid should be sent for culture at the time of surgical repair. The patient who has undergone penetrating trauma should be closely observed in the first few days after the injury and repair for evidence of a developing infection. Patients who have suffered a penetrating ocular injury with a low velocity foreign body in an agricultural or rural setting are at the greatest risk for infection.

Infection in an injured eye can be difficult to distinguish from the severe inflammation that often accompanies trauma to the eye. However, if a crescendo pattern of inflammation or pain is observed, Gram stain should be performed in search for gram-positive bacillus species, Gram-positive and Gramnegative rods, and fungi. Endophthalmitis

from bacilli is particularly fulminant and can lead to total destruction of the eye within 24 hours. It typically presents with severe pain early following repair. In any patient who develops severe pain after trauma, the diagnosis of bacillus endophthalmitis should be excluded in the absence of other definable causes. Recent reports have demonstrated that early intervention with a combination of vancomycin and gentamicin, or clindamycin and gentamicin can preserve the functional integrity of the eye.

TREATMENT OF

ENDOPHTHALMITIS

A. Acute Postoperative

Endophthalmitis

The Endophthalmitis Vitrectomy Study (EVS) was a randomized, multicenter clinical trial supported by the National Eye Institute that gave solid data on the role of pars plana vitrectomy and of systemic antibiotics in the management of acute endophthalmitis after

cataract surgery or intraocular lens implantation. It provides a framework by which this group of patients can be managed successfully. Immediatevitreoustapwithoutvitrectomyand with intravitreal antibiotic injection was found to be as efficacious as immediate vitrectomy and intravitreal antibiotic injection in cases where the presenting visual acuity was hand motions or better. In cases where the presenting acuity was light perception without hand motions, urgent vitrectomy resulted in a three times better rate of achieving visual acuity of 20/40 (33% versus 11%) and less than half the rate of deteriorating to less than 5/200 (20% versus 47%). The intravitreal antibiotics used were vancomycin 1.0 mg in 0.1 ml and amikacin 0.4 mg in 0.1 ml, and the concentrations did not vary between the vitrectomized and non-vitrecomized eyes. Treatment with intravenous ceftazadime and amikacin (or oral ciprofloxacin and amikacin) had no beneficial or adverse effect when intravitreal antibiotics were used.

In applying the results of the EVS, we suggest caution in making generalizations to other forms of endophthalmitis. The pathogens cultured in the EVS were bacteria of low-virulence associated with routine anterior segment surgery. Of the positive cultures, 90% were single organism Gram positives, and 68% were coagulase-negative. Only 6% were Gram-negative, all of which had media that was too opaque to allow visualization of a retinal vessel. Infections associated with filtration blebs or trauma yield a higher incidence of more virulent organisms such as Bacillus cereus, Streptococcus, Haemophilus influenza, and Gram-negatives.

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In that situation, earlier vitrectomy may have a more important role in saving vision.

The criteria set by the EVS serve as a guideline that should be modified by the clinical circumstance. In general, cases in which the ocular media are clear enough to allow visualization of the optic nerve and retinal vessels do not require vitrectomy and fare well with vitreal tap and injection. However, if the endophthalmitis is seen to be hyperacute in its progression and a more virulent organism is suspected, it may be prudent to perform a vitrectomy to mechanically remove the bacteria, especially if the operating theater is available without delay. Under such controlled circumstances, the EVS showed that the incidence of complications such as retinal detachment or phthisis with pars plana vitrectomy does not exceed that with vitreous tap and injection. Remember though, that visual prognosis relates most directly to the visual acuity at the time of therapy. Treatment of a rapidly deteriorating eye should never be delayed by unavailability of the operating theater, and it is certainly reasonable to perform a tap-inject procedure in the office with the thought of later proceeding to vitrectomy once it becomes possible.

Since Campochiaro showed macular infarction with Amikacin, many surgeons and institutionshaveshiftedtothesaferceftazidime not withstanding EVS insistence on merits and safety of Amikacin. It may definitely be used; but probably it is wise not to repeat it quickly, especially with vitrectomy, which increases the drug activity on retina.

In our clinical practice, in cases where gram-negative infection is not suspected, we usually substitute ceftazidime 1 mg in 0.1 ml for amikacin in order to reduce the potential for macular toxicity. Further, in order to decrease the retinal damage caused by inflammation, intravitreal dexamethasone in doses of 400 to 800 ug is given where fungal infection is not suspected. If the timing or clinical scenario suggest fungus, then amphotericin 5 ug in 0.1 ml is given and steroids are withheld.

As per the current knowledge, vancomycin is the single most suitable drug for acute, subacute, and selected cases of chronic endophthalmitis. While vancomycin and ceftazidime / amikacin is the preferred combination in acute endophthalmitis; even cefazoline and gentamicin (100 mg, not 400 mg in 0.1 mL) will do, when nothing else is available.

However, if repeat injections are required gentamicin / amikacin should be avoided. However, in cases with vision better than PL, even if intravitreal antibiotics successfully destroy the bacteria, the retina may continue to be damaged by the remaining inflammatory debris, and functional recovery is limited by potentially preventable pathologies such as macular edema. Early vitrectomy is mandatory in advanced cases.

As in the EVS study, we recommend injection of antibiotic into the anterior vitreous at the end of the vitrectomy, thereby avoiding placement of antibiotic in the irrigating fluid. A simple vitrectomy is performed without aggressive attempts to detach the posterior hyaloid or peel pre-retinal membranes.

Cutting and pulling of vitreous adjacent to inflamed or necrotic retina predisposes

to retinal tears that are usually difficult to repair (Figure 3). Because visualization is often limited by corneal opacity, care is taken to avoid risky manipulations. As in the EVS, we have not seen toxicity of antibiotics in vitrectomized eyes when concentrations proven to be safe in non-vitrectomized eyes are used.

The rare situation in which a rhegmatogenous retinal detachment occurs simultaneous with endophthalmitis is worthy of special mention because of its dismal prognosis. In that circumstance, the incidence of proliferative vitreoretinopathy is high and we advocate a careful but aggressive dissection of membranes and use of a long-acting retinal tamponade, usually silicone oil. Antibiotics are placed in the balanced salt infusion prior to the air-fluid exchange in order to ensure a safe concentration on the retina.

B. Acute Postoperative

Endophthalmitis in the

Non-Cataract/IOL Setting

Bleb Associated Endophthalmitis

In the era of full thickness filtration procedures, the reported rates of endophthalmitis were as high as 9%. After the introduction of partial thickness sclerotomies, the rates decreased to 0.3-1.5%. There is an increased risk of late endophthalmitis associated with inferiorly positioned trabeculectomies. The use of antiproliferative agents (5-fluorouracil and mitomycin C) improved the success rate of glaucoma filtering surgery but was

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associated with increased susceptibility to bleb infection. The antiproliferative agents are thought to disrupt conjunctival epithelial and stromal morphology which reduces the filtering bleb’s resistance to transconjunctival bacterial migration.

The hallmark of isolated bleb infection is a mucopurulent infiltrate within the bleb, associated with conjunctival epithelial defect and localized conjunctival hyperemia. There may be variable anterior segment inflammation; early on, the vitreous may remain quiet clinically and acoustically.

The bacteria associated with bleb related endophthalmitis must be capable of penetrating intact conjunctiva overlying filtering blebs. Encapsulated organisms such as Streptococcus species and Haemophilus influenza are prevalent.

Bleb-associated infection is classified according to severity. In stage I, bleb purulence may be accompanied by mild iridocyclitis. In stage II, moderate iridocyclitis is present. In stage III there is bleb purulence with marked anterior segment inflammation or vitritis.

Bleb cultures guide the antimicrobial choice, with more aggressive therapy for blebs infected with Streptococcus and Haemophilus, which are associated with worse visual outcomes. Cultures from the surface of the conjunctiva correlate poorly with results of anterior chamber and vitreous aspirates.

Stage I and II disease can be managed on an out-patient basis with aggressive fortified topical,periocularandsystemicantibiotics(usually a fluoroquinolone such as ciprofloxacin or

levofloxacin because of their high absorption with oral administration and good penetration into the eye). The choice for fortified topical antibiotics includes vancomycin and ceftazidime (both act synergistically by inhibiting biochemical pathways of bacterial cell wall synthesis). Topical fortified aminoglycosides are recommended over fluoroquinolones because of the lower observed rate of acquired bacterial resistance. Cases that fail to respond or show progression are treated as stage III disease.

0.4 mg/0.1 ml) together with topical and peri-ocular antibiotics.

The results of the EVS do not apply to bleb-associated endophthalmitis because of the low percentage of Streptococcus species and gram-negative cases in the study.

Post Traumatic

Endophthalmitis

Endophthalmitis is a particular devastating complication of posterior penetrating ocular trauma, affecting between 2-48% of eyes with these injuries. Gram negative organisms are implicated in 8-25% of cases of post-traumatic endophthalmitis. Bacillus species are commonly identified after injuries that involve farm material, so a high index of suspicion should be maintained in this clinical setting. These are ubiquitous gram positive spore forming rods that produce a fulminant en-

dophthalmitis that frequently results in loss of the eye.

Risk Factors include the presence of a low velocity intraocular foreign body (incidence of 6.8%), increased age of patient (> 50 years) as well as a delay of more than 24 hours in primaryrepairwhichcausesafour-foldincrease in the risk of infectious endophthalmitis (3.5% vs. 13.4%). Injuries contracted in rural settings have a higher incidence of endophthalmitis than those occurring in urban locations.

Indications for Treatment Include the Following

1.Inflammatory signs (including the development of a corneal ring abscess) and pain in excess of what is expected based on the injury and repair.

2.The culture results yield a virulent organism.

3.High risk cases with soil contamination or “dirty” intraocular foreign bodies, regardless of the severity of inflammation on initial examination. In such cases, urgent pars plana vitrectomy and intravitreal antibiotic injection are required.

An aggressive approach to suspected traumatic endophthalmitis is important. The Endophthalmitis Vitrectomy study (EVS) recommendations can not be generalized to the post traumatic settings because more virulent organisms are likely to be encountered.

Treatment involves immediate vitrectomy with cultures and debridement of necrotic tissue and removal of any intraocular foreign body. This is accompanied by the administra-

tion of systemic, subconjunctival, intravitreal, and topical antibiotics. Vitrectomy allows the concomitant treatment of intraocular effects of trauma such as retained lens cortex, vitreous hemorrhage and retinal breaks, as well as removal of infected vitreous and bacterial toxins. The choices for intravitreal antibiotic include vancomycin and aminoglycoside (gentamicin or amikacin) if B. cereus is cultured.

Although the EVS did not demonstrate benefit for intravenous antibiotic for postop- erative endophthalmitis, systemic intravenous antibiotic are considered standard care in post-traumatic endophthalmitis. The role of prophylactic intravitreal antibiotics in penetrating ocular trauma cases is controversial, with no prospective clinical studies published.

The visual prognosis is poor due to structural damage to the eye from the original injury and the increased virulence of organisms associated commonly with traumatic endophthalmitis.

C. Treatment of Chronic

Postoperative Endophthalmitis

Delayed onset endophthalmitis occurs six weeks to many months after the initial anterior segment procedure, often as the post-opera- tive anti-inflammatory and antibiotic drops are being weaned. In general this situation is caused by less virulent organisms such as Propionibacterium acnes, non-virulent Staphylococcus epidermidis, Candida species, Corynebacterium diphtheriae, and Listeria monocytogenes. These cases were not studied in the EVS. They can be associated with low-grade iridocyclitis and vitritis, mutton

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fat keratic precipitates, vitreous fibrin strands, and cystoid macular edema. Especially in cases of P. acnes, one may find retained lens material and white plaques of bacteria on the intraocular lens or within the capsular bag. The interval between surgery and presentation, and the severity of the symptoms often correlate with the virulence of the organisms. Many of these infections mimic an immunemediated process, and respond to topical steroids or antibiotics. Although they usually recur once the agents have been stopped, there have been well documented indolent infections with S. epidermidis and P. acnes that have been cured effectively with good visual outcome using a few weeks of topical antibiotics alone. There is generally no harm to attempting this conservative approach as long as the patient can be followed closely. However, when this approach fails, we generally favor a thorough vitrectomy procedure over tap / injection for several reasons. A larger volume of material can be obtained for culture, giving a higher rate of positive identification of these fastidious organisms. Also, this approach allows biopsy and removal of plaque material in which P. acnes often reside, and access to organisms that may be sequestered in the capsular bag. Finally, there can be advantages to mechanical removal of the organisms that have a long replication phase and are less likely to respond completely to a single dose of intravitreal antibiotics. As in the acute cases, it is important to obtain fluid from both the anterior chamber and vitreous cavity for culture, and to incubate samples in anaerobic broth and Sabouraud’s nutrient agar for two to four weeks to allow adequate growth. It has been our practice to try to retain the intraocular lens initially in most of these cases, but to remove it with

a secondary procedure if the inflammation persists.

D. Treatment of Fungal

Endophthalmitis

Fungal infection is likely to occur in the settingofadebilitatedorimmunocompromised host, intravenous drug abuse, intravenous catheters, trauma that involves the entry of vegetation into the eye, contaminated irrigating solutions, and in tropical climates where fungi may enter as a contaminant. Because fungi replicate slowly in the early stages, they usually do not present until two or three weeks have elapsed from the initial event. The infection can mimic a chronic bacterial endophthalmitis. Later, the fungus may incite a severe inflammation with vitreous opacities in a string-of-pearls appearance and posterior abscess. In endogenous cases, discussed below, rapidly multiplying chorioretinal infiltrates may be present.

The prognosis largely depends on which species is isolated. Candida albicans accounts for over two thirds of fungi, and can usually be eradicated with sequential injections of amphotericin B in doses of 5 to 10 ug every 48 to 72 hours. Because of the potential for severe retinal toxicity, this drug should be delivered slowly into the central vitreous cavity, well away from the posterior pole. In the setting of endogenous disease, especially with intravenous drug abuse or hyperalimentation, systemic candidemia is often present, and therapy with intravenous amphotericin B is recommended. If chorioretinal infiltrates are present with minimal vitreous involve-

ment, then intravenous therapy alone may suffice. Fluconazole is a triazole with excellent penetration into ocular tissues that can be administered orally. It is effective against candida species and is well tolerated with minimal side effects. It can be used in a combination with amphotericin in severe cases and as an alternative in cases of toxicity or intolerance.

Aspergillosis, the most common fungal infection in tropical climates, has unfortunately a grimmer prognosis. It can also be seen in immunocompromised patients after transplantation, patients with leukemia, intravenous drug abusers, and patients with endocarditis or chronic pulmonary disease, especially after treatment with corticosteroids. Visual prognosis is poor, partly because of the propensity for endogenous disease to involve the macula with chorioretinal and subhyaloid abscesses. The layering of white cells under the retina or internal limiting membrane can give a “pseudohypopyon” appearance. Treatment is similar to candidiasis but with a lower threshold for vitrectomy to debulk the fungal load. Itraconozole or Fluconazole should be considered for adjunctive systemic therapy, but the prognosis is poor overall.

Additional organisms that can cause endogenous fungal endophthalmitis include Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum, and Blastomyces dermatitidis. It is important to realize that in all of these infections, there is a high incidence of bilateral involvement and disseminated systemic disease that must be investigated, and that mortality has exceeded 10% in some reports.

E. Non-fungal Endogenous

Endophthalmitis

Although fungi are the leading cause of endogenous endophthalmitis, bacterial infections occur in a minority of cases. The bacteria reach the eye from a distant focus of infection or from a contaminated intravenous needle or catheter. A wide variety of pathogens have been documented and include Bacillus cereus, Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenza, Klebsiella pneumoniae, Neisseria meningitidis, and Propionibacterium acnes. Greenwald’sclassificationdividesthecondition into anterior focal, posterior focal, anterior diffuse, and posterior diffuse forms. If the disease is anterior and the vitreous cavity is not heavily involved, prompt treatment with intravenous antibiotics can result in recovery of vision. This is also true when a focus of infection is located in the retinal circulation before it has broken into the vitreous and disseminated. However, posterior diffuse disease, often the result of emboli into the central retinal artery, is usually associated with severe ischemia, necrosis, and loss of any meaningful vision.

The clinician must retain a high index of suspicion for this diagnosis and treat it as an ocular emergency. Cultures should be obtained from both the anterior and vitreous cavity, unless the infection is relatively

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confined to only one area. Paracentesis can be performed with a short 23 or 25 gauge needle through the limbus or pars plana, with removal of 0.1 ml of aqueous or 0.3 ml of vitreous fluid. If a focal abscess is present anteriorly, then an attempt should be made to aspirate it while keeping the needle over the iris to avoid injury to the crystalline lens (Figure 4). Blood cultures are also warranted. Unlike exogenous bacterial endophthalmitis, prompt and intensive intravenous antibiotics guided by infectious disease consultation are the mainstays of therapy. The consultant may also guide a search for occult distant infections in areas such as the urinary tract, heart valves, joints, skin, liver, and lungs. Topical and subconjunctival antibiotics may be useful for anterior segment disease but have no role in isolated posterior disease.

and ceftazidime 1.0 mg or amikacin 0.4 mg, with or without dexamethasone 0.4 mg.

Although prognosis depends in large part on factors outside the clinician’s control, such as virulence of the organism, immune status of the host, and size and location of the inoculum, the speed of recognition and intervention with antibiotics are the most important variables that we can control.

F. Surgical Strategies in Vitrectomy for Endophthalmitis

Endophthalmitis in the acute setting poses challenges to the vitreoretinal surgeon that can be overcome by a thoughtful approach. Often the procedures are done urgently, after hours, when an experienced ophthalmic support staff may not be available. If vitreous tap with antibiotic injection is planned, this can be done expeditiously in the clinic or minor operating room, but formulation of antibiotics at the appropriate dose becomes the greatest concern. If a decision has been made for vitrectomy, the patient should be transported without delay to the nearest facility that can provide the essential equipment.

If the patient is young and in good health, general anesthesia is often preferred. The inflamed eye is often painful and dif-

ficult to anesthetize with local techniques. Further, tissues will have a greater tendency to bleed, extending the duration of the procedure. Given the recommendations of the EVS above, it is more likely that patients going to surgery will have severe media opacity limiting intra-operative visualization. Fibrin membranes may cover the pupil and both surfaces of the intraocular lens, and the cornea may become opaque. Blind maneuvers can result in irreparable damage, so a careful and planned approach is helpful.

At the outset, the integrity of previous surgical wounds should be confirmed, and sutures added as needed to establish a good seal. If a pars plana infusion cannula is to be used, it is best placed at the beginning of surgery while the eye is still firm and entry is easy. Irrigation should not be used, however, until the cannula tip can be visualized within the vitreous cavity. Before then,