Saturday, 21 March 2015

Endophthaalmitis and Candida

you may find the language more technical than the condition leaflets.
Endophthalmitis is severe inflammation of the anterior and/or posterior chambers of the eye. Whilst it may be sterile, usually it is bacterial or fungal, with infection involving the vitreous and/or aqueous humours.Most cases are exogenous and occur after eye surgery (including cataract surgery) or penetrating ocular trauma, or as an extension of corneal infection. An increasing number of cases are occurring after intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) medications. Endophthalmitis may also be endogenous, arising from bacteraemic or fungaemic seeding of the eye.[1] Acute bacterial endophthalmitis is a medical emergency, because delay in treatment may result in vision loss.[2] When inflammation spreads throughout the globe and involves all the layers ± the peri-ocular tissues, the condition is known as panophthalmitis, a devastating fulminant condition which has a very bleak prognosis.

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Pathophysiology

Normally, the blood-ocular barrier prevents invasion from infective organisms but if this is breached (directly through trauma or indirectly due to a change in its permeability secondary to inflammation), infection can occur. Endophthalmitis can be:
  • Associated with surgery: acute or delayed postoperative.
  • Traumatic: bacterial or fungal endophthalmitis.
  • Endogenous: bacterial or fungal endophthalmitis.
  • Associated with corneal infection (microbial keratitis).
  • Associated with intravitreal injection.
  • Bleb-associated endophthalmitis
The most common pathogens in endophthalmitis vary by cause:[1] 
  • Coagulase-negative staphylococci are the most common causes of post-cataract endophthalmitis.
  • Coagulase-negative staphylococcal bacteria and viridans streptococci cause most cases of post-intravitreal anti-VEGF injection endophthalmitis.
  • Bacillus cereus is a major cause of post-traumatic endophthalmitis.
  • Staphylococcus aureus and Streptococcus spp. are important causes of endogenous endophthalmitis associated with endocarditis.
  • In Southeast Asia, Klebsiella pneumoniae causes most cases of endogenous endophthalmitis, in association with liver abscess.
  • Endogenous fungal endophthalmitis in hospitalised patients is usually caused by Candida spp., particularly Candida albicans.
  • Other pathogens which may be seen include:
    • Protozoans: Toxoplasma gondii, Toxocara spp.
    • Viruses: herpes simplex.
    • Bacteria: Pseudomonas aeruginosa.
Endophthalmitis is a rare condition. Most cases of exogenous endophthalmitis are postoperative, occurring after about 0.1% of cataract procedures. Patients aged over 85 who have had cataract surgery seem to be particularly prone.In a large Chinese study, post-traumatic endophthalmitis occurred in 11.1% of open-globe injuries.[3]One series of 10,000 patients undergoing intravitreal injection suggested an incidence of endophthalmitis of around 0.04%.[4] Endogenous endophthalmitis is even rarer than exogenous endophthalmitis (approximately 2-15% of all endophthalmitis cases). One American study reported an average annual incidence of 5 in 10,000 hospitalised patients.

Risk factors

  • In surgery:
    • Previous presence of infection (eg, bacterial conjunctivitis).
    • Poor surgical technique.
    • Contaminated intraocular lens.
  • In accidental injury:
    • Retained infected foreign material, particularly if this is organic.
  • Ophthalmic risk factors:
    • Contact lens wear (where there is poor hygiene).
    • Chronic corneal ulceration.
  • Non-ophthalmic risk factors:
    • Debility.
    • Distant infection (eg, indwelling catheter).
    • Immunosuppression.
    • Intravenous drug use.
    • AIDS.
  • Presentation is usually acute, with eye pain and decreased vision.
  • The eyelid may be swollen (about one third of cases)
  • Occasionally the condition is not painful.
  • Hypopyon is a common finding, and the appearance of the eye may be hazy.
  • In exogenous endophthalmitis, infection is confined to the eye. There is no fever and minimal, if any, peripheral leukocytosis.

Associated with surgery

Acute postoperative endophthalmitis
This is the most common form of endophthalmitis It arises one to several days after surgery, most presenting at 1-2 weeks. There is sudden decrease of vision and increasing eye pain. Patients also notice red eye, ocular discharge, and blurring.
  • Signs - without the slit lamp, you may see:
    • Lid oedema.
    • Intense conjunctival injection and chemosis.
    • Corneal oedema.
    • Hypopyon (pus in the anterior chamber, which looks like a white fluid level sitting at the base of the iris).
    • Decreased red reflex.
    • Decreased visual acuity.
    • Slit-lamp examination will reveal severe inflammation in the anterior chamber and the vitreous, with cells and fibrin, vitreous inflammation and retinitis.
Delayed postoperative endophthalmitis
This develops a week to a month (or more) after surgery. It may even take years to develop but the average is nine months. There is insidious decrease of vision, gradually increasing redness and minimal or no pain.
  • Signs - without the slit lamp, look for:
    • Conjunctival injection.
    • Hypopyon
    • Clumps of exudate (little white blobs) in the anterior chamber, which you may see on the iris or around the pupillary margin.
    • The cornea looking cloudy (due to oedema).
    With the slit lamp all the above are clearly seen, as are anterior chamber and vitreous inflammatory reactions.
Bleb-associated endophthalmitis
When drug therapy fails in the treatment of glaucoma, patients may go on to have surgery. A trabeculectomy is a procedure that creates a fistula which allows the aqueous to drain from the anterior chamber. A so-called bleb is formed over this area, seen as a smooth, raised patch just above the cornea, under the upper lid. Occasionally, this gets infected ('blebitis') but when the vitreous is also involved, it becomes a bleb-associated endophthalmitis.
  • Signs - there is a short history of rapidly worsening pain and vision, with marked redness, and the bleb itself will appear milky white. There may be a hypopyon too.

Not associated with surgery

Traumatic endophthalmitis
  • Signs - these are the same as with acute postoperative endophthalmitis. Some organisms (eg, Bacillus spp.) may result in a severe reaction and lead to pyrexia, leukocytosis, proptosis and a corneal abscess.
Endogenous bacterial endophthalmitis
Decreased vision in an acutely ill patient should prompt thoughts of endogenous bacterial endophthalmitis. It also typically occurs in an immunocompromised individual or intravenous (IV) drug user. S. aureus is the most common organism involved, followed by Streptococcus pneumoniae and Streptococcus viridans. Gram-negative organisms such as Escherichia coli can also be a cause.
  • Signs - these may include lid and conjunctival oedema and the cornea may appear cloudy. Ophthalmoscope examination may also reveal flame-shaped retinal haemorrhages. If slit-lamp examination is possible, you may see hypopyon, an anterior chamber and vitreous inflammatory reaction and microabscesses on the iris. Panophthalmitis may ensue.
Candida-associated endophthalmitis[5]
Intraocular candidal infection, although uncommon, can be bilateral. Candidal chorioretinitis and endophthalmitis are complications of systemic candidiasis with extension of the fungal pathogens to the uvea and retina. The condition may also arise in similar conditions to endogenous bacterial endophthalmitis including IV drug use. It should also be suspected where there is a history of a penetrating injury with an organic foreign body (eg, plant or soil-contaminated object). Surprisingly, there appears to be no association with AIDS or any other immunocompromised condition. There is, however, an association with abdominal surgery and there is a theory that candidal overgrowth is involved. Diabetes is another risk factor and an increase in vitreous glucose has been identified in patients with candida-associated endophthalmitis.
  • Signs - symptoms include decreased vision, floaters and pain. It is usually bilateral and may follow an indolent course. Ophthalmoscopy will reveal fluffy yellow-white retinal lesions (which look a bit like cotton balls) ± retinal haemorrhages. If you can examine the patient with a slit lamp, you will see widespread inflammation and a hypopyon.
Other fungal endophthalmitis
Infection with Candida spp. is by far the most common cause of fungal endophthalmitis but other fungi are occasionally found - notably Aspergillus spp. (found in soil, decaying matter and organic debris) cryptococci (notably found in pigeon droppings) and the Coccidioides spp. (agricultural and construction workers are at risk). These remain rare infections although the incidence is increasing, possibly related to IV drug use, the use of chemotherapy in cancers and immunosuppressive therapy in transplant patients, as well as the increasing survival of debilitated patients.
  • Signs - presenting features are as for the other forms of endophthalmitis but visual loss may be less significant.
Endophthalmitis associated with microbial keratitis
The cornea can become infected in a variety of situations, particularly in contact lens wear (high-risk factors include extended wear and poor hygiene), where there is pre-existing corneal disease and, occasionally, in other conditions (eg, chronic blepharoconjunctivitis or dacrocystitis, tear film deficiency or topical steroid therapy). If this is severe, there may be progressive ulceration of the cornea which can lead to a bacterial endophthalmitis. Such patients are usually already under the care of an ophthalmic team. There are a number of causes of red eye postoperatively, including:
  • Raised intraocular pressure - as a direct result of the procedure.
  • Retained lens material - if the crystalline lens is not fully removed at the time of cataract surgery, the small remaining piece can cause an intraocular inflammatory reaction. This is an autoimmune reaction to the exposed lens protein. The lens material can often be seen with a slit lamp if the patient is asked to move their eyes (it is seen floating up in the aqueous or vitreous before settling down again when the eye is still).
  • Aseptic endophthalmitis - is more likely to occur after a prolonged procedure and results from excessive tissue manipulation. Symptoms and signs are usually mild.
  • Inflammatory reactions - can occasionally occur in response to the substances used in cataract surgery (eg, those used to sterilise the intraocular lens).
  • In an immunocompromised host where there might be fungal endophthalmitis - other differentials include cytomegalovirus retinitis, toxoplasmosis and a number of other conditions that have similar lesions and that will be assessed by the ophthalmologist (eg,  infections with herpes simplex, nocardia, aspergillus and cryptococci).
Remember that postoperative and trauma patients can also develop a red eye due to a new problem that is unrelated to the procedure or trauma.See separate article Red Eye for fuller discussion of the general causes of this condition. Initial diagnosis is made on slit-lamp examination. An ultrasound scan may also be of help. However, diagnosis is ultimately confirmed by taking a sample of vitreous for microbiological culture (diagnostic surgical vitrectomy). This is done in theatre and may also be a therapeutic procedure if the vitreous is entirely removed (to reduce the infectious load); intraocular antibiotics can be administered at the same time.In the case of endogenous bacterial endophthalmitis and candida-associated endophthalmitis, a full infection screen is warranted (FBC, blood cultures and culture of all indwelling lines and catheters). The latter may also prompt a search for possible immunocompromise.Polymerase chain reaction (PCR) may be helpful in differentiating between fungal and bacterial infection.Other investigations may be required to exclude differential diagnoses (eg, erythrocyte sedimentation rate (ESR) to help rule out rheumatoid arthritis) and associated conditions (eg, creatinine to assess renal function).CT or MRI scan of the orbit may help to rule out other ophthalmic conditions. These are different depending on the type of endophthalmitis as discussed above in 'Risk factors' and 'Presentation'. Endophthalmitis is a medical and ophthalmological emergency.
  • Suspected acute endophthalmitis requires emergency admission.
  • Suspected delayed postoperative endophthalmitis needs urgent referral within 24 hours.
  • Most patients will be admitted for a diagnostic work-up and antimicrobial treatment.

Bacterial endophthalmitis

Treatment of bacterial endophthalmitis includes direct injection of antibiotics into the vitreous, and vitrectomy in more severe cases.
  • Systemic antibiotics are indicated in endogenous endophthalmitis; their role in exogenous bacterial endophthalmitis is controversial.
  • Visual outcome depends on the virulence of the bacterial pathogen and the speed with which treatment is given.[2]
  • Repeated intravitreal injections of antibiotics may be necessary if there is no response to the initial therapy.
  • Many eyes that receive prompt and appropriate treatment will recover useful vision.[1] 
  • Some patients will additionally be prescribed steroids once fungal infection has been ruled out. These are to limit the amount of inflammatory-induced damage.
  • Topical cyclopegics also play a role in controlling the symptoms.

Candidal endophthalmitis

Treatment for candidal endophthalmitis have not been fully evaluated through clinical trials.[5][6] Traditional systemic therapies have been amphotericin with or without flucytosine or fluconazole.
  • Vitrectomy with or without intravitreal amphotericin injections has been advocated, particularly for patients with moderate-to-severe vitritis and substantial loss of vision.
  • Information on new antifungal agents for endophthalmitis is limited..
  • Voriconazole may be helpful in fluconazole-resistant strains.
  • In general, it appears that chorioretinitis infections can be more readily cured with most systemic antifungal agents, whereas more aggressive treatment, often including vitrectomy with or without intravitreal antifungal administration, is needed for patients with endophthalmitis with vitritis.
These are mainly of decrease or loss of vision. Chronic pain may become an issue in some patients.
  • The visual acuity at the time of the diagnosis and the causative agent are most predictive of outcome.
  • Acute postoperative endophthalmitis has a poor prognosis with 55% of eyes managing 6/60 or less.
  • Chronic postoperative endophthalmitis usually responds well to steroids initially but then tends to become refractory to treatment.
  • Successfully treated bleb-associated endophthalmitis is at risk of recurring infections. In the event that vision is lost and the eye becomes chronically painful, enucleation (removal of the globe) may have to be considered.
  • Endogenous endophthalmitis has a worse prognosis than exogenous endophthalmitis and some patient groups, such as those with diabetes, do less well.
A Cochrane review in 2013 looked at antibiotic prophylaxis in cataract surgery and a found a reduced risk of endophthalmitis with antibiotic injections during surgery compared with topical antibiotics alone: One of the included studies, the European Society of Cataract and Refractive Surgeons (ESCRS) study, was performed using contemporary surgical technique and employed cefuroxime, an antibiotic commonly used in many parts of the world.Clinical trials with rare outcomes require very large sample sizes and are quite costly to conduct; it is therefore unlikely that further clinical trials will be conducted to evaluate this further.[7]  This is an inflammatory condition affecting both eyes that occurs after a penetrating injury (accidental or surgical) to one of the eyes. See separate article Sympathetic Ophthalmia for more details.
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Further reading & references

  1. Durand ML; Endophthalmitis. Clin Microbiol Infect. 2013 Mar;19(3):227-34. doi: 10.1111/1469-0691.12118.
  2. Durand ML; Bacterial endophthalmitis. Curr Infect Dis Rep. 2009 Jul;11(4):283-8.
  3. Zhang Y, Zhang MN, Jiang CH, et al; Endophthalmitis following open globe injury. Br J Ophthalmol. 2010 Jan;94(1):111-4. Epub 2009 Aug 18.
  4. Simcock P, Kingett B, Mann N, et al; A safety audit of the first 10 000 intravitreal ranibizumab injections performed by nurse practitioners. Eye (Lond). 2014 Jul 18. doi: 10.1038/eye.2014.153.
  5. Khan FA, Slain D, Khakoo RA; Candida endophthalmitis: focus on current and future antifungal treatment options. Pharmacotherapy. 2007 Dec;27(12):1711-21.
  6. Sallam A, Lynn W, McCluskey P, et al; Endogenous Candida endophthalmitis. Expert Rev Anti Infect Ther. 2006 Aug;4(4):675-85.
  7. Gower EW, Lindsley K, Nanji AA, et al; Perioperative antibiotics for prevention of acute endophthalmitis after cataract surgery. Cochrane Database Syst Rev. 2013 Jul 15;7:CD006364. doi: 10.1002/14651858.CD006364.pub2.
  8. Chan C; Sympahetic ophthalmia, American Uveitis Society, 2003
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