ENDOPHTHALMITIS 2016

INTRAVITREAL INJ & PPV

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DR DINESH MITTAL DR SONALEE MITTAL

DRISHTI EYE HOSP VIJAYNAGAR INDORE

OUTLINE

LAYOUT OF A OPERATION THEATER

LAYOUT OF A OPERATION THEATER

WALLS FLOORS AND DOORS

OPERATING ROOM

VENTILATION CONTROL

DISADVANTAGES OF FORMALIN

ENVIRONMENTAL DECONTAMINATION

ENVIRONMENTAL DECONTAMINATION

CHOICE OF DISINFECTANT

DISCIPLINE IN OPERATION THEATER

GLOVING

OPERATION THEATER ENVIRONMENT

OPERATION THEATER ENVIRONMENT

CLEANING INSTRUMENTS

STERILIZATION

EFFICACY OF STERILIZATION

STERILE PRODUCTS

SAMPLES TO BE COLLECTED

MICROBIOLOGICAL TESTING OF OT AIR ( SETTLE PLATE )

WHAT TO DO AT CLUSTER INFECTION

WHAT TO DO AT CLUSTER INFECTION

WHAT TO DO AT CLUSTER INFECTION

WHAT TO DO AT CLUSTER INFECTION

WHAT TO DO AT CLUSTER INFECTION

RISK FACTORS FOR ENDOPHTHALMITIS

RISK FACTORS FOR ENDOPHTHALMITIS

RISK FACTORS FOR ENDOPHTHALMITIS

RISK FACTORS FOR ENDOPHTHALMITIS

RISK FACTORS FOR ENDOPHTHALMITIS

RISK FACTORS FOR ENDOPHTHALMITIS

INTRODUCTION• Infectious endophthalmitis is a potentially devastating condition involving the internal structures of the eye. It is one of the most feared complications of cataract extraction and other intraocular surgeries. Rarely, it can occur endogenously from a systemic nidus of infection.

INTRODUCTION•Endophthalmitis is classified on the basis of the source of the infection, as exogenous, which is the most common subtype, or endogenous. The avascular densely packed collagenous matrix of the cornea and sclera serves as a potent barrier against infectious infiltration in normal eyes.

INTRODUCTION•Violation of these structures, typically by surgery or trauma, makes eye susceptible to entry of pathogenic organisms, and may lead to exogenous endophthalmitis. Bacteria are often causative agents in these cases. There are typically no associated systemic findings such as fever and minimal, if any, peripheral leukocytosis.

Endogenous endophthalmitis• Endogenous endophthalmitis occurs in otherwise healthy eyes in association with transient or persistent bacteremia or fungemia. It is observed most frequently in immunosuppressed patients and intravenous drug users, and less commonly in patients with cardiac valvular disease, persistent sites of infection elsewhere in the body, and in those undergoing dental work. Fungal infections are most common, but a third of patients will present with bacterial endophthalmitis, often caused by gram-negative species .

Exogenous Endophthalmitis

Classification of Endophthalmitis• Infectious endophthalmitis is classified by the events leading to the infection and by the timing of the clinical diagnosis. The broad categories include postoperative endophthalmitis (acute-onset, chronic or delayed-onset, conjunctival filtering-bleb associated), posttraumatic endophthalmitis, and endogenous endophthalmitis.

Classification of Endophthalmitis•Miscellaneous categories include cases associated with microbial keratitis, intravitreal injections,or suture removal. These categories are important in predicting the most frequent causative organisms and in guiding therapeutic decisions before microbiologic confirmation of the clinical diagnosis .

TRAUMA

•The risk of endophthalmitis following open globe injuries ranges from 4.2 to 7%. In contrast, following closed globe injuries, endophthalmitis is exceedingly rare. Staphylococcal species are most common causative agents in trauma-related endophthalmitis, and some species such as Bacillus cereus are seen only in trauma. The source of the infection is typically the penetrating material .

TRAUMA• The rate of infection rises dramatically to 10–15% when an IOFB is present and if the repair is delayed beyond 24 hours of the injury. Even without overt infection, prophylactic intravitreal antibiotics should be considered at the time of the IOFB removal, since in nearly a quarter of patients cultures of the IOFB will be positive for bacteria, and risk of intravitreal antibiotics is generally low. In rural settings, where organic material contamination is common, endophthalmitis following penetrating ocular trauma achieves rates as high as 30%, with Bacillus species isolated in 46% of cases and polymicrobial isolates in 42%.

Cataract surgery•Post-cataract endophthalmitis is categorized on the basis of the time to onset following surgery, as acute (within 6 weeks) or delayed. The incidence of endophthalmitis after cataract extraction is reported to be 0.04–0.15%. Some authors suggest an increase in the incidence of endophthalmitis beginning in the late 1990s/2000, in parallel with the increased use of clear cornea cataract wound placement .

Cataract surgery•Post-cataract endoph is typically associated with defects in surgical wound and violation of lens capsule, which can provide a route of entry for infectious agents. The patient’s own periocular flora is source of infection in majority of cases of endophthalmitis. In 68–82% of post-cataract endophthalmitis cases, an identical genetic or molecular signature was present in vitreous isolates and commensal bacteria occupying the patient’s conjunctiva, eyelids or nose .

CATARACT SURGERY•The Endophthalmitis Vitrectomy Study (EVS) was a major prospective randomized clinical trial analyzing the treatment of acute post-op endoph, and it identified coagulase negative Staphylococcus in 70% of cases; less common were Staphylococcus aureus in nearly 10%, Streptococcus species in 9%, Enterococci in 2%, and gram-negative organisms in 6%.

Cataract surgery• In pediatric patients undergoing intraocular surgery, the risk of endophthalmitis is estimated to be 0.07–0.16%, with 82% of cases presenting by the third post-operative day. Pediatric endophthalmitis is typically caused by gram-positive bacteria; 47% of cases are associated with nasolacrimal duct obstruction or upper airway infection .

Cataract surgery•Among various antiseptics studied, 5% povidone iodine solution was able to reduce incidence of endoph . In delayed onset endoph , Propionibacterium acnes is the most commonly implicated pathogen, accounting for nearly 40% of

isolates . It has a subtle presentation and indolent course .

Glaucoma filtration procedures• Glaucoma surgery is associated with endophthalmitis in 2.1–

2.6% of cases. Endophthalmitis following glaucoma surgery, unlike postcataract infections, tends to be delayed and is often associated with prior episodes of blebitis . Diabetes, use of anti-metabolites as well as inferior bleb location increases risk and hastens onset of endophthalmitis. Delayed onset bleb-related endophthalmitis is associated with Streptococcus species (25%) and gram-negative organisms, particularly

Haemophilus influenzae (18%).

Intravitreal injections• Intravitreal injections of triamcinolone have a 0.87% incidence of infectious endophthalmitis, possibly due to inhibition of immune function against inadvertently introduced pathogenic agents. Accordingly, the intravitreal injections of ANTI VEGF drugs , including ranibizumab, are associated with significantly lower endoph rates of 0.02–0.08%.

Intravitreal injections•Diabetics may be at higher risk, however. The majority of the cases are caused by Streptococcus or Staph species representing commensal flora of ocular adnexa and oropharynx. The risk of infection may be lessened by decreasing oropharyngeal droplet transmission at time of the injection .

Intravitreal injections• The use of compounding pharmacies, which involves the parceling of a single medication such as bevacizumab into multiple intravitreal injections, may increase incidence of infection and has been associated with local outbreaks of endoph. Avastin vial may be adulterated also .The use of postinjection antibiotics does not appear to decrease the frequency of endoph, but, in fact, may lead to selection of drug resistant bacteria in the nasopharynx and on the ocular surface .

AVASTIN INDUCED ENDOPHTHALMITIS• Vial itself may be adulterated and hence containing toxins .

So even if the vial is opened on the table and pt given intravit injection pt. will develop symptoms like TASS . In case of avastin symptoms will be localized in posterior segment so this should be called TOXIN POSTERIOR SEGMENT SYNDROME and not TOXIN ANTERIOR SEGMENT SYNDROME ( TASS ) . These symptoms will develop in few hours and are a type of sterile reaction to toxins . And if the avastin gets infected during compounding then infective endoph will develop after some days .

ORGANISMS THAT CAUSE ENDOPHTHALMITIS•Bacteria, fungi, protozoa, and parasites are all capable of producing endophthalmitis . Bacteria are the most common group of organisms causing endophthalmitis. Gram-positive organisms are responsible for 60–80% of acute infections in all large series. These organisms vary widely in their virulence and, therefore, in their effect on the eye.

INFECTIVE AGENTS CAUSING ENDOPHTHALMITIS

POST-OPERATIVE ENDOPHTHALMITIS•Worldwide, the reported incidence of post-operative endophthalmitis is 0.04- 4%. Post cataract surgery incidence is 0.265% (more with clear corneal incision), post keratoplasty 0.382% and post vitrectomy 0.05%. The incidence of bleb associated infection is 0.2%-9.6%.

POST-OPERATIVE ENDOPHTHALMITIS•Though rare, it is potentially the most feared and devastating complication of intraocular procedures and can lead to a permanent, complete loss of vision. Endophthalmitis has been associated with severe visual loss in 20% of patients. A series of endophthalmitis cases may force a temporary shutdown of the operation theatre.

Patient symptoms•Patient symptoms indicative of endoph include ocular pain, diminished vision and headache. Although pain is an important symptom, it is not universal. It is important to differentiate infective endoph from sterile post-op inflammation. Toxic Anterior Segment Syndrome (TASS) is an acute postop inflammatory reaction in which a noninfectious substance enters the anterior segment and induces toxic damage to the intraocular tissues. Almost all cases occurred after uneventful cataract surgery.

TASS• In TASS, most develop symptoms within 12-24 hrs , there is decrease in visual acuity, corneal edema is from limbus to limbus, there is moderate to severe AC reaction with cells, flare, hypopyon and fibrin, pupil may be dilated and non-reactive and IOP may be normal or raised.

TASS•Post operative endophthalmitis may be early or delayed. Most common causative agents are gram positive coagulase negative organisms. However in India, gram negative organisms and fungi are also important in aetiopathogenesis. Differentiation is important as the management and prognosis of TASS is significantly different . Delay in diagnosis leads to delay in initiating appropriate treatment.

Patient symptoms•Endophthalmitis should be suspected when there is pain and increased in AC reaction on slit lamp examination on first post operative day or later . However pain may be absent in 25% cases. Decreased glow on distant direct ophthalmoscopy has high sensitivity but low specificity on first post operative day.

Patient symptoms• On subsequent post operative days, decrease in vision

following initial improvement along with pain should immediately raise the index of suspicion. Presence of exudates in vitreous on indirect ophthalmoscopy is 100% specific. • Presence of hypopyon and vitreous exudates is usually

diagnostic of endophthalmitis. • If there is NO HYPOPYON, role of distant direct

ophthalmoscopy, slit lamp examination, indirect ophthalmoscopy and ultrasound B scan very important in deciding surgical intervention, rule out other causes like masquerade.

Patient symptoms•Slit lamp examination helps to see dilatability of pupil, wound margin (many cases related to suture removal). • In cases with poorly dilating pupils and significant AC reaction (+++) and best corrected visual acuity better than 6/60, sterile reaction should be considered and treatment started with intravenous bolus steroids and topical steroids and antibiotics.

Patient symptoms•However if BCVA <6/60, endophthalmitis should be considered and patient should be administered intravitreal antibiotics. An USG B scan may aid in the diagnosis with non dilating pupils and severe AC reaction by demonstrating vitreous echoes. •Presence of vitreous exudates clinches the diagnosis of endophthalmitis.

Antimicrobial therapy• The target area for microbial therapy in endoph is vitreous cavity. Intravitreal therapy is the cornerstone of antimicrobial administration, whereas role of subconj and systemic antibiotics is more controversial. Because most cases of endoph manifest as acute fulminant infections, the initial antibiotic administration is usually made without culture results to identify the organism definitively. The choice of agent administered initially is therefore empirical . Broad-spectrum coverage is important, and choice depends in part on microbes expected in a given clinical setting.

Antimicrobial therapy• Gram-positive bacteria predominate in all types of acute

endoph, but specific organisms and their frequency vary. Microbes causing acute postoperative endoph are most often the pt. own bacterial flora. Staphylococcal species account for more than two-thirds of all cases, but Gram-negative organisms are also encountered. In acute traumatic endophthalmitis, Gram-positive organisms are the most commonly identified, but this includes a high incidence of Bacillus species. In traumatic endoph, the microbes reflect not only patient’s flora but also contaminants from the scene of the trauma. Gram-negative infections and mixed infections are encountered more often than in acute postoperative cases.

Antimicrobial therapy• In delayed postoperative endoph, Propionibacterium acnes, nonvirulent staphylococci, and fungi are most often the causative agents. When infection is associated with a filtering bleb, Streptococcus species are identified in a high percentage of cases.

Antimicrobial therapy• Characteristics for ideal drugs for the treatment of bacterial

endophthalmitis include the following: • 1. Bactericidal properties. Because the eye is an immune-

privileged site, like the central nervous system, a bactericidal drug rather than bacteriostatic agent is preferred.• 2. Broad spectrum of coverage. Coverage must include Gram-

positive organisms, especially methicillin-resistant staphylococci and Bacillus species in trauma cases, and Gram-negative organisms.• 3. Excellent therapeutic ratio (activity/toxicity) after intravitreal

injection.

Antimicrobial therapy• 4. Good therapeutic ratio after IV injections. Most antimicrobials

penetrate the vitreous cavity poorly after IV injection because of the blood–eye barrier. Intravitreal antimicrobial levels are only rarely reported to reach levels above the MIC for organisms usually seen in endophthalmitis after IV or oral administration. Hydrophilic antibiotics (including aminoglycosides and β-lactam antibiotics) have less potential for penetration into the eye than lipid-soluble compounds. On the other hand, there is significant systemic toxicity to the antimicrobials commonly used in treating endophthalmitis, particularly the aminoglycosides and amphotericin. Furthermore, some combinations of antibiotics have a favorable spectrum of coverage (e.g., vancomycin and aminoglycosides), but their toxicities are additive when used simultaneously.

Antimicrobial therapy• 5. Favorable pharmacokinetic properties. Intraocular

inflammation enhances penetration of certain antibiotics. Vitrectomy has been shown to enhance the penetration of cefazolin, vancomycin, and ceftazidime into the eye. Repeated IV dosing may contribute to increased penetration into the vitreous cavity after IV administration, particularly in inflamed and previously operated eyes. After intravitreal administration antibiotics are eliminated through either an anterior or posterior route. Aminoglycosides are eliminated anteriorly, and the β-lactam antibiotics are removed posteriorly. Vitreous removal shortens the half-life of all antimicrobial agents studied in animal models. Lens removal decreases the half-life of antibiotics eliminated anteriorly.

Antimicrobial therapy• Inflammation may increase the half-life of antimicrobials

excreted posteriorly, such as cefazolin; blocking agents such as probenecid may also increase the half-life of these drugs. The half-life for anteriorly excreted drugs such as gentamicin and amikacin is decreased by inflammation. A higher initial dose is preferred whenever possible to allow the drug to remain at levels greater than the MICs of common pathogens for a longer period. Known activity of the drug is also an important • consideration in the choice of the antibiotics. If drugs are given

in equivalent concentrations, the one with higher activity against suspected organisms should be chosen.

Antimicrobial agents•Four groups of antimicrobials are commonly prescribed in endoph: •(1) cephalosporins; •(2) aminoglycosides; •(3) fluoroquinolones; and• (4) antifungal agents.

Cephalosporins• The cephalosporins are synthetic penicillins active against the

bacterial cell wall. They are well tolerated systemically, and cefazolin has been established to be a relatively safe drug when 2.25 mg is injected intravitreally. All the cephalosporins have good broad-spectrum coverage for Gram-positive and some Gram-negative organisms, but the first-generation drugs are weak against enterococcus and meticillin-resistant staphylococcal organisms. Injection of cefazolin (2.25 mg) into the aphakic eye produces levels greater than the MICs for approximately 48 hours. Ceftazidime is a promising antibiotic for Gram-negative coverage in endophthalmitis therapy because it has good cerebrospinal fluid penetration and excellent Pseudomonas coverage. In a study of 37 Gram-negative isolates from cases of endoph, 80% were susceptible to ceftazidime.

Vancomycin

• Vancomycin has been recommended as the antibiotic of choice for Gram-positive coverage. Its coverage is purely Gram-positive, but its spectrum includes all of the staphylococcal species, Bacillus, and P. acnes. The mechanism of vancomycin is inhibition of cell wall assembly, in addition to damaging protoplasts and inhibiting RNA synthesis. The intraocular therapeutic ratio for vancomycin is good, although the half-life suggests that therapeutic concentrations will be maintained for only about 48 hours after intravitreal injections. Vitreous sampling after intraocular injection in human infection has suggested that potentially therapeutic levels may persist for 3–4 days after initial injection depending on the initial dose.

Aminoglycosides

• Aminoglycosides have a spectrum that includes both Gram-positive and Gram-negative organisms. They are chosen particularly for their Gram-negative coverage in endoph . The mechanism of action for aminoglycosides is to inhibit protein synthesis. Unfortunately, the intraocular therapeutic ratio after intraocular injection is a source of problems. Retinal vascular infarction has been frequently reported after gentamicin, and it has also been noted after amikacin administration. Tolerated dosages may be higher for amikacin than for gentamicin, but all of the aminoglycosides cause retinal changes after higher intravitreal dosages. The half-life of amikacin is approximately 8 hours in inflamed, vitrectomized eyes.

Aminoglycosides

• Because of the limitations in the amount given for the initial dosage, the concentration of these antibiotics remains above the MIC for only 24–36 hours after administration. The therapeutic ratio for treatment of ocular disease after IV administration is also unfavorable because of systemic toxicity. Penetration of gentamicin into the eye after IV administration has been studied in both rabbits and humans. It does not reach therapeutic levels in traumatized rabbit eyes, normal rabbit eyes, or human eyes with various ocular diseases after single doses.

FLUOROQUINOLONES

• The quinolones are broad-spectrum antibiotics with both Gram-positive and Gram-negative coverage. Their mechanism of action is thought to be inhibition of DNA synthesis. The second-generation drugs are ciprofloxacin and ofloxacin, while levo-floxacin is a third-generation agent. The fourth-generation drugs, gatifloxacin and moxifloxacin, have significant potential in the prophylaxis and treatment of endophthalmitis. Initial reports of the therapeutic ratio of ciprofloxacin after intraocular injection suggest that intraocular toxicity occurs at low dosage levels. Fluoroquinolones penetrate the blood–ocular barrier more readily than do several of the other classes of antimicrobials. Ciprofloxacin has reasonable penetration after oral administration, but many ocular pathogens have developed resistance to it.

FLUOROQUINOLONES

• After two doses of oral administration levofloxacin achieves concentrations in the aqueous and vitreous above the MIC (90) for many Gram-positive and Gram-negative pathogens but not for Pseudomonas aeruginosa. Studies of penetration of gatifloxacin and moxifloxacin into noninflamed eyes undergoing vitreous surgery after oral administration of two doses demonstrated that the percentages of serum concentrations achieved in the vitreous and aqueous were 26.17% and 21.01%, respectively. These levels are above the MIC (90) for most of the pathogens producing human disease. These include: Staphylococcus epidermidis, S. aureus, Streptococcus pneumoniae, S. pyogenes, Enterococcus faecalis, Proteus mirabilis, Escherichia coli, and Propionibacterium acnes, among others. Notably, however, neither agent achieved vitreous MIC (90) for Pseudomonas aeruginosa and moxifloxacin did not reach the MIC (90) for Bacteroides fragilis.

ANTIFUNGAL AGENTS

• Amphotericin has been considered the gold standard in antifungal therapy. Its mechanism of action is the alteration of membrane permeability by combination with sterols and fungal cytoplasmic membranes. The intraocular therapeutic ratio has not been well studied, but the usual recommended dosage is 5 μg/mL. After IV there are significant systemic complications, including renal toxicity. Penetration into the eye is also relatively poor. After intraocular injection, the half-life has been reported to be 9.1 days. The half-life is further decreased by inflammation and vitreous removal. Vitrectomy and oral fluconazole have been reported to treat Candida endophthalmitis successfully, with fewer side-effects.

ANTIFUNGAL AGENTS• Fluconazole has significant penetration into noninflamed eye after oral administration. Voriconazole is a triazole antifungal agent which is a second-generation synthetic derivative of fluconazole It demonstrates a broad spectrum of action, including Aspergillus species, Candida species , and has a low MIC (90) for many organisms. After oral administration, therapeutic levels are achieved in aqueous and vitreous in non- inflamed eyes. Uses of intravitreal voriconazole for fungal endoph have been reported.

Pars plana vitrectomy

• PPV plays a role in many phases of endoph therapy. As initial therapy it is validated by the EVS results only for acute postcataract extraction infections in eyes presenting with vision of hand motions or less. In addition to use as initial therapy in many of these clinical settings, PPV should also be considered for eyes not responding to an original tap-and-inject strategy, and may be necessary to clear vitreous opacities in eyes cured of infection when spontaneous clearing does not occur.

Preoperative evaluation

• A careful and extensive history should be taken. Clinical details such as systemic infectious disease, type of eye injury, or previous surgery may hold important clues to the identity of the infecting organism. Particular attention should be paid to the length of time from the surgical insult or trauma to the onset of symptoms and to the time that has passed since symptoms began. Previous antibiotic or corticosteroid therapy should be noted. A thorough ocular examination should include a careful search for any possible route of entry for the infecting organism.

Preoperative evaluation

• The effects of the inflammation should also be noted: corneal clarity and thickness, condition of any surgical wound, degree of anterior-chamber reaction, hypopyon, clarity of the vitreous, visibility of the retina, and presence or absence of a red reflex. USG can define the degree of condensation of the vitreous, determine whether the retina is attached, and identify choroidal swelling. Preoperative ERG findings may have a predictive value for postoperative visual result, but this has not yet been well defined.

MANAGEMENT• At present, best choice of intravitreal antibiotics is

Vancomycin (1 mg in 0.1 ml) combined with Ceftazidime (2.25 mg in 0.1 ml) in separate syringes. • Alternatively, Vancomycin may be combined with

Amikacin (400 μg in 0.1 ml). • Topical treatment comprises Moxifloxacin 1 hourly or

Fortified Cefazoline + Tobramycin 1 hourly along with cycloplegics in the form of Atropine every six hourly. Intravenous Ciprofloxacin 200 mg twice daily is required in very severe cases.

Intravitreal antibiotics • Intravitreal antibiotics are the key to management

because levels above the minimum inhibitory concentration of most pathogens are achieved, and are maintained for days. They should be administered immediately after culture specimens have been obtained. Antibiotics commonly used in combination are ceftazidime, which will kill most Gram-negative organisms (including Pseudomonas aeruginosa) and vancomycin to address Gram-positive cocci (including methicillin-resistant Staphylococcus aureus).

Intravitreal antibiotics • ○ The antibiotics are injected slowly into the mid-

vitreous cavity using a 25-gauge needle. • ○ After the first injection has been given, the syringe

may be disconnected but the needle left inside the vitreous cavity so that the second injection can be given through the same needle; alternatively a second needle can be used.

Medications•Various antibiotics may be considered for intravitreal injection . The most commonly used medications in suspected bacterial endophthalmitis include vancomycin and ceftazadime. Intravitreal vancomycin provides broad coverage for over 99% of gram-positive organisms and ceftazadime is effective against 100% of gram-negative bacteria observed in post-operative endophthalmitis .

Surgical Intervention• The results of EVS study are still applicable to post-cataract endophthalmitis cases today, with some modifications. In post-cataract patients presenting with intraocular inflammation and a visual acuity at the level of light perception, PPV with injection of intravitreal antibiotics appeared to improve the visual outcomes compared with intravitreal antibiotics alone. For patients with visual acuity of hand motion or better, PPV with intravitreal antibiotics appeared to provide no additional visual benefit compared with intravitreal antibiotics alone .

Surgical Intervention• The main goals of PPV in endophthalmitis are to obtain sufficient tissue for diagnosis and to debulk the pro-inflammatory debris. In practice, a culture result of the removed material alters clinical management in less than 5% of cases. While the EVS included limited vitrectomy, more extensive debridement may provide better outcomes. Removal of the IOL is typically not required, except in cases of chronic low-grade endophthalmitis associated with P. acnes resistant to medical therapy .

WHEN TO DO PPV• Oral Steroids administered as 1-1.5 mg / kg single dose along

with oral antibiotics. Ciprofloxacin 750 mg twice daily for 7-10 days usually preferred although currently many clinicians prefer oral Gatifloxacin or Moxifloxacin. After intravitreal antibiotics, patient is monitored for 24-36 hours. If there is worsening, patient has to be taken up for surgical intervention in the form of PPV . If there is no worsening, medical treatment can be continued for 48 hours following which decision regarding additional intravitreal antibiotics or surgical intervention is to be taken. Improvement in fundus glow with decrease in hypopyon is indicative of clinical improvement. Medical treatment should be continued.

WHEN TO DO PPV• in situations where there is a partial response to

intravitreal antibiotics with resolution of hypopyon but persisting AC reaction (3-4+), further intravitreal antibiotics are not preferred, conservative medical management is continued and patient is readied for surgical intervention. • In situations where there is no response to intravitreal

antibiotics or in very severe infection, RADICAL pars plana vitrectomy with peeling of hyaloid and base dissection is required. There is no role for core vitrectomy in this situation.

PPV• IOL removal during vitrectomy for endophthalmitis may be

indicated in severe endoph, P acne endoph, fungal endoph and recurrent endoph. • The eye is usually quite where signs are more prominent

than symptoms. Vitreous Balls, fungal granuloma may be seen. Smears, cultures may help if on initial treatment, there is no/ partial response or worsening, Vitrectomy is the only hope. Treatment includes oral and intravitreal voriconazole (50-100 ug) or intravitreal amphotericin (5-10 ug). Steroids should be stopped. Oral/ intravenous antibiotics, cycloplegics and topical antibiotics are usually continued

SURGICAL TECHNIQUES

• GA is preferred because of the difficulty of obtaining adequate LA for an inflamed, painful eye. LA may be adequate for shorter procedures or if the patient’s medical condition warrants this approach. The first technical problem that confronts the surgeon is placement of the infusion cannula. Because the media is almost always too cloudy for the surgeon to be able to visualize a pars plana port, this infusion cannot be used for the initial stages of the operation.

SURGICAL TECHNIQUES• Because the incision and placement of the infusion port are easier in a firm eye, it is often worthwhile placing an inferotemporal port with sutures, reserving its use for later in the procedure, once the location of the tip in the vitreous cavity can be verified. The clarity of the cornea and anterior chamber and the presence of the crystalline lens or a pseudophakos will determine the first incision into the eye after cannula placement. If the anterior vitreous can be easily seen, a pars plana incision 3.5 mm from the limbus can be the first incision.

SURGICAL TECHNIQUES• If light is not needed during the initial portion of the procedure, a bent needle or other blunt infusion port can be positioned in the center of the pupillary space, where its position can be monitored. This infusion can be turned on at this stage so that the incision through the pars plana for the cutting instrument may be made in a firm eye. That incision is also made 3.5 mm posterior to the limbus. The initial instrument placed in the eye may combine both light and infusion. Alternatively, a full-function instrument combining infusion, light, cutting, and suction is a good option for these cases.

SURGICAL TECHNIQUES• The anterior chamber often contains significant amounts of

fibrin and hypopyon. Because the cornea invariably has some combination of epithelial edema, folds, and cells deposited on the posterior surface, the iris and central anterior vitreous are often impossible to visualize adequately. Initial incisions may be made in the limbus at 9.30 and 2.30 clock positions, modifying the location as necessary depending on condition of the previous surgical wound and on the presence of a filtering bleb. Fluid is infused into the anterior chamber as inflammatory debris is removed with the suction and cutting instrument . This may also be accomplished with a single incision and a small-gauge instrument combining infusion, cutting, and suction .

SURGICAL TECHNIQUES• . The use of a single incision reduces the flexibility of the

surgical approach, however. When two incisions are used and when it is necessary to switch the cutting instrument from one site to the other, it is useful to remove the cutting instrument from its site and then replace it with a second infusion on a blunt needle the same size as the cutting instrument. Only then is the initial infusion removed and the cutting instrument replaced in its site. This allows the pressure to be maintained at a constant level, minimizing chances of hemorrhage and making passage of instruments through limbal incisions easier. An inflammatory membrane usually extends continuously over lens or pseudophakos and on to surface of iris. When a pseudophakos is present, the lens need not be removed; attempting to do so may increase the risk of bleeding.

SURGICAL TECHNIQUES• The inflammatory membrane, however, should be removed from its

surface for better visualization of posterior segment. It may be initially incised with a myringotomy blade or other sharp needle and then elevated for removal with a cutting instrument . It may also be engaged with a hooked needle and rolled on to the needle. Removal of an inflammatory membrane from the crystalline lens should begin over the iris, close to the pupillary border, if it is believed that the lens can be spared. Often, because of poor dilation of the pupil and poor visualization of the internal structures, the lens in phakic eyes must be removed. The fastest way to accomplish this is with fragmentation through pars plana incisions, although young, soft lenses can often be removed with cutting instruments. In severe cases the cornea and anterior chamber may be totally opaque. In theses eyes, a temporary keratoprosthesis can be used, followed by a penetrating keratoplasty .

SURGICAL TECHNIQUES•Material for culture and stain should be removed from the eye early in the case. Because anterior-chamber samples frequently do not render positive culture results, attention should be directed to obtaining an adequate vitreous sample. In most surgical setups, the tubing that comes from the suction–cutting portion of the instrument can be opened. Alternatively, a very short piece of tubing is attached to the egress port of the vitrectomy probe . A sterile syringe is connected, and the vitreous is withdrawn with manual suction.

SURGICAL TECHNIQUES• 0.2 mL is removed before starting infusion into the eye to obtain an undiluted sample. The material is then immediately sent to the laboratory for Gram- and Giemsa-stain as well as cultures on blood agar, chocolate agar, brain–heart infusion, and Sabouraud’s media or broth and in thioglycolate broth. It is important to obtain specimens for culture before any antibiotics are injected into the eye. The vitrectomy is now progressively carried posteriorly. The vitreous removal is performed initially in the center of the vitreous cavity. Pockets of more heavily infiltrated vitreous are sometimes located; in the aphakic eye, peripheral depression may be used to bring these into view.

SURGICAL TECHNIQUES• Aggressive removal of all infiltrated vitreous in the basal area should not be attempted because this often results in retinal tears. The presence of a posterior vitreous detachment, on the other hand, allows more complete vitreous removal. If the vitreous is still attached, a judgment must be made about the amount of vitreous to be removed. The cutting of vitreous adjacent to inflamed or necrotic retina will often cause retinal breaks; these are difficult to seal and may result in failure of the case.

SURGICAL TECHNIQUES• In eyes with posterior vitreous detachment, a white mound of inflammatory debris may be visible over the posterior pole. This should be approached with care and may be gently aspirated into the cutting port. If the mound proves to be solid and adherent, small amounts can usually be removed, but in most cases it is unwise to attempt to remove large portions. In some instances material is flocculent and equivalent to an unorganized hypopyon; this can be gently sucked up with vacuum techniques .

SURGICAL TECHNIQUES• If visibility is so poor that vitreous posterior to the central

area cannot be adequately defined, repeated attempts should be made to clear the anterior chamber. Membranes can also be present on the posterior surface of the lens, and these should be removed. If good visibility cannot be obtained, it is better to discontinue the procedure than to risk retinal damage by cutting posteriorly with inadequate visualization. The procedure is completed by closing all incisions in a water-tight manner and injecting intraocular antibiotics. After closure of the conjunctival incisions, subconjunctival antibiotics are often injected. The major intraoperative complications to be feared are hemorrhage and retinal detachment.

Elevation of fibrin membrane from lens and iris to mobilize for cutting.

A short piece of tubing connects a syringe to vitrectomy probe to obtain a vitreous sample.

Vacuuming removal of “hypopyon” from macular area.

SURGICAL TECHNIQUES Retinal breaks are a major problem. A choroidal hemorrhage may be devastating and can destroy the eye. The best way to avoid this complication is to keep intraocular pressure at a constant level during the entire procedure, thereby preventing hypotony. If choroidal hemorrhage does develop, intraocular pressure should be immediately raised to high levels in an attempt to close bleeding vessel. Breakdown of the original surgical wound is also occasionally encountered. Resuturing the wound with broader bites may be necessary. Since the introduction of small gauge vitrectomy, the use of 23G and 25G instruments has become more popular in the treatment of infectious endophthalmitis. However, many surgeons choose to routinely suture all sclerotomies at the end of these cases.

Postoperative management• If treatment is proceeding well, patients usually have a dramatic improvement in ocular pain by the first postoperative day. Nonetheless, some form of analgesic, including narcotics, is often required. Resolution of disease can be monitored in part by progressive reduction in pain. Antibiotics given intravitreally at time of surgery maintain high therapeutic levels for 24–48 hours. In bacterial disease, necessity for repeat intravitreal injection is not known with certainty; levels exceeding minimal bactericidal levels are present for at least 24–36 hours after most intravitreal injections .

Postoperative management• . Drops may also be prepared by the hospital pharmacy in highly

concentrated doses; administered from 5 to 20 times daily, they may have a booster effect but probably do not significantly increase intraocular concentrations. Not all infections are cured by a single dose of injected antimicrobial. If the inflammation appears to worsen the physician should suspect that the infectious process remains active. A repeat tap and injection of antibiotics, chosen on the basis of the culture results, should be considered; if the media appears significantly opaque, or if the initial therapy was only injection of antibiotics, a vitrectomy may be considered. If the initial culture sensitivities show that the organism is resistant to the antibiotic originally injected, injection of an appropriate antibiotic is recommended .

Postoperative management• Vancomycin, ceftazidime,cefazolin, or a fluoroquinolone may

be useful when a longer duration of antimicrobial effect is desired than the 24–48 hours provided by intravitreal injection. Second operations are frequent in patients with endophthalmitis. In the EVS , 35% of all eyes needed some secondary procedure. Opacities in the vitreous cavity may continue to interfere with vision, even if the eye responds well in terms of inflammatory signs. The retina should be monitored at regular intervals with ultrasound if the surgeon cannot be sure by indirect ophthalmoscopy that it remains attached. Removal of these opacities may be undertaken with a repeat vitrectomy as an elective procedure once the eye becomes quiet.

Complications• The cornea is often edematous in the early postoperative period.

Epithelial edema usually clears within the first week if the endothelium has not undergone major damage; stromal edema will also slowly clear. Persistent epithelial defects may occasionally be seen, and their healing can be compromised by the frequent use of topical medications. Pigmented cells may remain on the posterior surface of the cornea for months. If epithelial edema does not clear and the eye seems otherwise salvageable, a corneal graft may be considered. Elevated pressure usually responds to medical management and improves as the inflammatory process resolves. Persistent hypotony, which not only contributes to poor corneal clearing but is also usually associated with persistent inflammation and a progressive downhill course, even in the presence of a sterile vitreous cavity should raise the suspicion of a leaking wound site.

Complications• Ultrasonography may reveal choroidal detachment; the only

management currently available is a vigorous attempt to control the inflammatory process medically. Inflammatory signs (usually more flare than cells) can persist for many weeks after surgery, especially if the initial disease was severe. Bacterial products such as endotoxins in Gram-negative infections and exotoxins in Gram-positive infections may persist, even after successful vitrectomy, resulting in a recurrence of vitreous cavity fibrin and cells 24 hours after an adequate vitrectomy. If there is no sign of slow but steady improvement, the ultimate outcome is almost uniformly poor, and phthisis is the usual result.

Complications• Cataract may also develop in the postoperative period if the

crystalline lens has been left in place. Cataract removal can also be performed electively when the eye becomes quiet. If the ultrasound or clinical examination indicates the presence of significant vitreous opacities associated with the lens change, a pars plana approach may be used for fragmentation of the lens and removal of the vitreous opacities during the same procedure. Retinal detachment is a feared complication of vitrectomy for endophthalmitis. Retinal detachment occurred in 8.3% of eyes in the EVS. Tears that occur at the time of surgery are managed as outlined earlier. Unrecognized intraoperative tears, such as entry-site tears, can result in a detachment soon after surgery. Necrotic retina may also break down, creating an atrophic retinal break.

Complications• Standard buckling procedures may help in many cases, but

these may be difficult to perform because of the inability to see the fundus clearly on account of corneal opacity, poor dilation of the pupil, persistent opacity of the media, haze on the surface of an IOL, or opacification of the vitreous base. These retinal detachments can sometimes be repaired successfully, but they are reportedly the major cause of failure in most series. Anatomic success was achieved in 78% of the cases in the Endophthalmitis Vitrectomy Study, but the occurrence of detachment was correlated with a poor visual outcome .

Complications• Proliferative vitreoretinopathy is a major risk in eyes with

detachment; sympathetic ophthalmia has also been reported.Despite anatomic success, some eyes see poorly. Postoperatively a small percentage of eyes injected with aminoglycosides at surgery develop whitening of the macular area with intraretinal hemorrhages in the posterior pole. Fluorescein angiography demonstrates shutdown of the capillaries and arterioles supplying the macula and vision is frequently poor. Histologic examination of similar appearing lesions produced experimentally in primates by injection of gentamicin shows extensive destruction of the nerve fiber layer.

PRACTICAL EXAMPLES

DURING CATARACT SURGERY THERE WAS UNFORESEEN SOME COMPLICATIONS

REACTION DISAPPEARED AFTER INTENSIVE STEROIDS

ENDOPHTHALMITIS DEVELOPED ON 3RD POST OP DAY .TREATED WITH INTRAVITREAL VANCOMYCIN 1MG AND CEFTAZIDIME 2.25 MGPOST INTRAVITREAL INJ PT IMPROVED .

PPV WITH IOL REMOVAL DONE IN THIS CASE AS THIS CASE DOES NOT RESPOND TO INTRAVITREAL INJ OF VANCOMYCIN AND CEFTAZIDIME .

CONCLUSION•Endophthalmitis remains a devastating complication of intraocular surgery and penetrating ocular trauma despite recent advances in diagnosis and treatment. Two-thirds of cases are postoperative, and 20–25% occur after penetrating trauma. Gram-positive organisms predominate in incidence and usually fare better than Gram-negative infections, with Staph epidermidis having a better prognosis than S. aureus. Fungal endoph accounts for 5–10% of all cases.

CONCLUSION• Intraocular antibiotics are well established as the mainstay of treatment for endoph because of the poor penetration of antibiotics into the vitreous cavity when administered by other routes because of the blood–retina barrier. Antibiotics are sometimes injected into the vitreous cavity as the only intravitreal therapy, whereas on other occasions they are combined with pars plana vitrectomy .

CONCLUSION• Pars plana vitrectomy has the advantage of removing bacteria and their toxins and clearing the ocular media, allowing a more rapid visual recovery. The eye is sterilized more quickly and reliably. Most authors recommend vitrectomy as the initial therapy for fungal infections and for the secondary structural changes, such as vitreous opacification, occurring after chronic infections such as Toxocara canis. Most authors recommend vitrectomy for Propionibacterium acnes infections and for traumatic endophthalmitis.

CONCLUSION• In bacterial infections, immediate vitrectomy is recommended for the most severe infections, including clinical settings such as filtering blebs, which are known to have a high incidence of virulent organisms. Vitrectomy is then followed by intraocular antibiotic injection. Although severity of infection is difficult to define precisely, mild to moderate infections are managed with immediate vitrectomy by some authors, but others recommend initial intraocular antibiotic injection, followed by vitrectomy only if the disease worsens.

CONCLUSION• The Endophthalmitis Vitrectomy Study demonstrated that vision with only light perception was an indication for immediate vitrectomy based on improved results in these eyes compared with a strategy of vitreous tap and injection of antibiotics. Results of therapy for endoph have improved in the last decade. Reasonable return of vision is often achieved in cases with negative culture results and infections with S. epidermidis and some fungi. Smaller percentages of eyes infected with S. aureus and even fewer with Gram-negative organisms survive with recovery of ambulatory vision.

CONCLUSION

• Infections after trauma have a poorer prognosis than postoperative cases after cataract extraction; postoperative pars plana vitrectomy eyes and eyes with filtering blebs do poorly. The length of time from onset of infection to initiation of therapy and differences in virulence from one strain of bacteria to another are other important factors in outcome.

THANK YOU

DR DINESHDR SONALEE