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OCULAR FINDINGS IN FUNGAL ENDOCARDITIS
ABSTRACT
Infectious endocarditis secondary to fungus is a condition usually seen in patients with a
history of intravenous drug use, intravenous antimicrobial use, among other factors.
Discussion of treatment, management and retinal findings will be presented.
CASE REPORT
A 59 year old Caucasian male is being referred to rule out ocular manifestations of yeast
infection secondary to fungal endocarditis. He complains of many little dots in both eyes
which seemed to move when his eye moves and that they have been present for about a
week. He has no ocular pain, no ocular discomfort, no discharge, no flashes of light, no
history of ocular surgery or trauma. His medical history is positive for hepatitis C,
recently diagnosed diabetes (HbA1c 5.6%), depression, post-traumatic stress disorder,
colon polyps, congestive heart failure and aortic valve replacement (1/13/2009)
complicated by acute endocarditis (Candida per infectious disease). Medications include:
acetaminophen, enoxaparin, micafungin, omeprazole and warfarin.
Best corrected visual acuities are 20/25 OD, OS. Ocular motility and pupillary testing are
unremarkable. Slit lamp exam reveals meibomian gland capping, pinguecula, clear
cornea, a deep/open/quiet anterior chamber and grade one nuclear sclerosis. Intraocular
pressures are13mmHg OD and 14mmHg OS. Fundus examination reveals a flame
hemorrhage inferior nasal to the optic nerve OS and several large blot/intraretinal
hemorrhages throughout the posterior pole OS>OD. Examination of the periphery
reveals no signs of active or past infection/inflammation. Retinal vessel examination
reveals minor crossing changes as well as flame hemorrhages near the vasculature
throughout the posterior pole. A Roth spot is present nasal to the optic nerve OS.
A retinal specialist is consulted and concurs with the examination findings and diagnosis
of intraretinal hemorrhages and a Roth spot most likely secondary to fungal endocarditis.
Baseline fundus photos are obtained. The patient is referred to the ophthalmology clinic
retinal specialists for a one month follow-up. Two positive Candida albicans cultures are
obtained by infectious disease. Previous treatment includes amphotericin B, but he does
not tolerate it. Patient is on micafungin IV daily. He suffers from a hemorrhagic stroke 2
days after optometry appointment and respiratory failure; prognosis poor. Patient is
undergoing palliative care in the ICU.
The patient was lost to follow-up due to death secondary to stroke complications,
respiratory arrest and endocarditis.
Discussion
Infectious endocarditis is a rare condition in which an agent, usually bacterial or fungal in
nature, attaches itself to the valves of the heart and forms vegetation. Infective
endocarditis is infection of the heart's endothelial lining classically manifested by
vegetations on the cardiac valve surface. The development of endocarditis depends upon
several factors. The valve surface must be altered to allow for colonization. The surface
can be altered by blood turbulence, hypercoagulable states, congenital cardiac disease,
rheumatic and degenerative valvular disease, intravenous drug abuse, prosthetic heart
valves, indwelling catheters, and pacemaker wires. The damaged endothelial cell surface
triggers local deposition of fibrin and platelets, which produce the vegetations that
characterize thrombotic endocarditis. The vegetations usually are located along the line of
closure of the valve leaflet. The signs and symptoms of bacterial and fungal endocarditis
are very similar with fever, heart murmur and petichiae being most common. Other less
frequent signs include Osler’s nodules (painful nodules on the fingers and toes), Janeway
lesions (painless hemorrhagic plaques on the palms of the patient’s hands and soles of
their feet), splinter hemorrhages, conjunctival hemorrhages and Roth spots.
Superficial flame-shaped hemorrhages originate from the postarteriolar superficial
capillary bed or thee radial peripapillary capillary system. The flayed, flame-shaped
edges result from the blood seeking lines of least resistance in the contour of the nerve
fiber layer. Often these hemorrhages may have a white center, presumable from white
blood cells, these are Roth spots. These hemorrhages only last a few weeks before being
resorbed and have no particular effect on vision. These hemorrhages are usually confined
to the posterior pole more common in the peripapillary area; especially when there is a
local area of retinal hypoxia as the oxygenated arterial supply is compromised.
A Roth's spot was originally associated specifically with cases of subacute bacterial
endocarditis. The term is reserved for a hemorrhage surrounding a white center. The
white center may represent an area of the following: (1) focal accummulations of white
blood cells in inflammatory vascular disease, (2) cotton-wool spots surrounded by a
hemorrhage, (3)leukemic cell foci surrounded by a hemorrhage, (4) fibrin surrounded by
a hemorrhage.
The clinician must attempt to ascertain the underlying cause, allow time for resorption,
observe for other signs of hypoxia (neovascularization) and determine the underlying
systemic cause.
Conjunctival petechial hemorrhages, iris abcesses, superficial or deep retinal
hemorrhages, focal abscesses, vasculitis, choroidal neovascular membrane formation, and
endogenous endophthalmitis are the major complications of infective endocarditis. The
classic ocular sign of infective endocarditis is a Roth spot (a white-centered hemorrhage).
Retinal arteriole occlusion may produce cotton wool spots, and branch or central retinal
artery obstruction. The inflammatory emboli also can cause a choroiditis that can lead to
choroidal neovascular membrane formation. Endogenous endophthalmitis is the most
severe ocular complication of infective endocarditis. The treatment of endogenous
endophthalmitis usually involves identification of the underlying organism and
aggressive systemic treatment with the appropriate antibiotics. If there is clinical
evidence of virulent endophthalmitis associated with significant vitritis or hypopyon the
physician also should consider intravitreal antibiotics, possibly in conjunction with pars
plana vitrectomy.
Several small, retrospective, nonrandomized reports suggest that systemic treatment with
vitrectomy and intravitreal antibiotics may have better visual results than systemic
treatment alone. Conversely, endogenous endophthalmitis may be the initial presenting
sign of infectious endocarditis in a small subset of patients. A full systemic evaluation,
including cardiac ultrasonography, should be performed in all patients with endogenous
endophthalmitis.
Candida albicans accounts for about 24 percent of fungal endocarditis cases. Arterial
embolization is more common in fungal endocarditis as compared to bacterial; likely a
reflection of the vegetations associated with the disease process. These emboli are often
found in the cerebral circulation, extremities and the gastrointestinal tract. Diagnosis
consists of blood culturing and echocardiography which often reveals valvular
vegetations which are large. A study identifying risk factors for systemic emboli in
infective endocarditis concluded that the main risk factor for systemic emboli was the
size of the vegetation. When the size of the vegetation was >10mm risk was 57 percent as
compared to 22 percent when <10mm. Mobility of the vegetation was also identified as a
risk factor: 48 percent if the vegetation was mobile versus 9 percent if it was fixed. Sex,
age, pathogen, type of valve, and the number and position of the vegetations were not
found to be risk factors. Overall, mobile vegetations greater than 10mm in size were
associated with increased risk of an embolic episode. Almost 50 percent of patients with
acute infectious endocarditis suffer an embolic event during their illness and 20 percent
initially present with embolization.
One major difference between fungal and bacterial endocarditis is large emboli occur in
the fungal form but not bacterial. Fungal infections, specifically Candida, often affect the
aortic and mitral valves causing perforation, congestive heart failure and arterial emboli.
Risk factors for endocarditis due to a fungal agent include: history of cardiac surgery
valve replacement, IV drug use, long term IV antibiotics, central venous catheter and a
compromised immune system.
Ischemic or hemorrhagic strokes may commonly occur in those patients with infective
endocarditis. Cerebral infarctions are related to the occlusion of intracranial arteries due
to embolic material derived from vegetation. These occlusions may also have a
hemorrhagic component. Larger vegetations put the patient at higher risk for ischemic
strokes. Also, the vegetations are contaminated with microorganisms which necrotize the
brain tissue causing abscess. Some hemorrhagic strokes may be related to this necrotizing
arteritis or to the rupture of a mycotic aneurism.
Fungal endocarditis, among other problems, can lead to septic retinitis. Septic retinitis is
noted when circulating organisms in the blood stream reach the retina; rarely causing
endophthalmitis or panophthalmitis. More often in embolic retinitis the changes noted
consist of cotton-wool spots, retinal edema and retinal hemorrhages (some with white
centers); also known as Roth spots. When Roth spots are noted one’s differential should
include leukemia, septic chorioretinitis (secondary to bacterial or fungal endocarditis) and
diabetes most commonly. Less common differentials would include pernicious anemia,
sickle-cell disease, systemic lupus erythematosus and scurvy.
Treatment consists of both antifungal agents as well as valve replacement as
recommended in the 2009 Infectious Diseases Society of America guidelines.
There are also cases of patients with whom medical treatment alone seemed to be
sufficient; however, this is questioned due to relapses being so common and follow-up
extending several years. Therapeutic treatment consists of long term high dose
amphotericin B (with or without flucytosine) for at least six weeks. After this six week
period it is common to use a step down approach with fluconazole.
Conclusion
Infectious endocarditis is a rare condition in which an agent, usually bacterial or fungal in
nature, attaches itself to the valves of the heart and forms vegetation. It may present in the
eye in various forms: Roth spots, endophthalmitis, iris abscesses or as neovascularization.
A clinician should be aware of these presentations and order a full systemic evaluation,
including cardiac ultrasonography, should be performed in all patients with endogenous
endophthalmitis as well as blood work-ups in those patients with retinal hemorrhages.
References
Deprele, C et. al., Risk Factors for Systemic Emboli in Infective Endocarditis, European
Society of Clinical Microbiology and Infectious Disease, CMI, 10, 46-53.
Freischlag, J.A., Septic Peripheral Embolization from Bacterial and Fungal
Endocarditis, Annals of Vascular Surgery, Volume 3, No. 4, 1989.
Del Brutto, Oscar H., Infections and Stroke, Cerebrovascular Diseases and Stroke, 28-39,
2005.
The Wills Eye Manual, Third Edition. Rhee, Douglas J, Pyfer, Mark F. editors.
Scheie and Albert, Textbook of Ophthalmology, Ninth Edition. Copyright 1977.
Primary Care of the Posterior Segment, Third Edition, Alexander.
Brian T. Landrum, O.D., M.S.
Dayton VAMC Eye Clinic (112E)
4100 W. Third St.
Dayton, OH 45428
937-268-6511 ext. 3674