Roth Spots

From EyeWiki

Roth Spots

Disease Entity

Roth Spots ICD-10: H35.60


Roth Spots are defined as a white centered retinal hemorrhage and are associated with multiple systemic illnesses, most commonly bacterial endocarditis. Originally described by Moritz Roth in 1872 while at the University of Basel, Roth spots were first seen in individuals with bacteremia secondary to subacute bacterial endocarditis.[1][2] The retinal findings Roth made in 1872 were described as round, oval or flame-shaped hemorrhages with a central white spot. Although originally described by Roth, Roth spots earned their name only later by the (biologist) Litten in 1878. Litten made more detailed observations of these entities and claimed they appeared in approximately 80% of cases of subacute bacterial endocarditis, thus cementing the hallmark association.[3][2] However they can be seen in a wide variety of conditions, and more recent research has found that only 2% of patients with endocarditis had Roth spots present on their retina.[4] Though Roth spots are usually thought of as pathognomonic for bacterial endocarditis, they can occur in a number of conditions (Table 1).

Risk Factors

Risk factors for subacute bacterial endocarditis include IV drug use, immunodeficiency, poor dentition or dental infection, structural heart disease, valvular disease, and prosthetic valves.[5]

The presence of an underlying disease promoting abnormal retinal blood vessels (e.g., diabetes and hypertension) is linked to the development of Roth spots. Patients with genetic predisposition to leukemia/ lymphoma are at higher risk of developing Roth spots.


A series of investigations beginning in the 1960’s demonstrated that the white center of Roth spots represent a fibrin thrombus, platelet aggregates, and infiltrating red blood cells at the site of a previous vessel rupture. These findings resulted in a more coherent understanding of the pathogenesis of Roth spots. Specifically, rupture of retinal capillaries results in the extrusion of whole blood and subsequent platelet adhesion to the damaged endothelium. The resulting coagulation cascade then results in a platelet-fibrin thrombus, which results in the pale lesion appearing at the center of hemorrhage red lesion.


Roth believed these spots represented disseminated embolic foci of bacterial abscesses originating from infective vegetation on heart valves. Early investigators into the histopathology of Roth spots were surprised by the lack of leukocytes in the white center of the lesions examined in patients who died of sepsis. Instead, they discovered these areas showed faint cellular staining, indefinite boundaries of the capillary endothelium, and diffuse hyaline changes. 

Roth’s initial suspicion that these represented foci of bacterial abscess was thus called into question in light of these histopathological findings. It is now believed that Roth spots are the result of retinal capillary rupture and intraretinal hemorrhage.

A common thread found in the conditions associated with Roth spots (Table 1) is a predisposition for endothelial dysfunction allowing for retinal capillary disruption. Histological examination reveals that the white centered lesions are composed mostly of fibrin, which represents extravasation and a fibrin-platelet plug at the site of vessel rupture. [2]

Primary prevention

Roth spots alone are largely asymptomatic. Visual disturbance due to Roth spots is rare but can occur with macular involvement. Detection of Roth spots on fundoscopy can be a sign of underlying disease, and if found incidentally, referral to a primary care physician or internist for evaluation and work-up of systemic disease is suggested. 


Initial evaluation is based largely on a thorough history, review of systems, and physical exam. 

If there is clinical suspicion for endocarditis, labwork should include CBC with differential, erythrocyte sedimentation rate, C-reactive protein, and blood cultures should be drawn, with antibiotic treatment started immediately after blood cultures are taken. A transthoracic echocardiogram should be obtained to evaluate for definitive signs such as vegetations.

Tests such as peripheral blood smears should be obtained if history and physical raise clinical suspicion for leukemias, lymphomas, anemias, thrombocytopenia, etc.

HIV antibody testing should be done if the patient has any risk factors or suggestive findings on history or physical exam. 

If carbon monoxide poisoning is suspected quantification by co-oximetry of a blood gas sample should be obtained. [6]

HgB A1C and plasma glucose should be performed if there is any clinical suspicion of diabetes mellitus.

Multimodal Imaging: spectral-domain optical coherence tomography (SD-OCT) shows that Roth spots affect the inner retina, with thickening of the nerve fiber layer (NFL) and hyperreflective deposits below the internal limiting membrane (ILM) that cause a shadowing effect. These hyperreflective deposits are thought to represent the fibrin-platelt hemostatic complex. [7][8] On fundus autofluorescence (FAF) and fluorescein angiography (FA), Roth spots will demonstrate hypoautofluorescence and hypofluorescence due to blockage similar to other types of intraretinal hemorrhages.[8]

Medical History

As Roth spots are non-specific ophthalmic findings, a thorough history should be taken with particular attention to past medical history of prior infections, cardiac history (e.g., prosthetic heart valves), dental history, IV drug use, immunodeficiency, and other chronic conditions including diabetes, hypertension, anemia, and known hematologic disorders. 

A full review of systems related to infective endocarditis and bleeding disorders such as fevers, chills, night sweats, unexplained weight loss, fatigue, abnormal bleeding or bruising and shortness of breath should be reviewed. 

Physical examination

Roth spots are signs of systemic illness and the patient's vital signs and overall hemodynamic stability should be assessed. 

On fundoscopic exam Roth spots will appear as round flame shaped hemorrhage with a white/pale center (variable in size), commonly in the posterior pole. Full dilated exam with scleral depression evaluating for other retinal abnormalities that may accompany Roth spots may give insight to the underlying disease process (e.g., other signs of diabetic retinopathy). 

If suspicious for endocarditis, additional possible ophthalmic findings on complete eye exam include conjunctival hemorrhage, retinal hemorrhage, cotton-wool spots, retinal infarction, chorioretinitis, and rarely endophthalmitis. Non-ophthalmic exam findings include Janeway lesions, Osler nodes, splinter hemorrhages, petechiae, and cardiac murmurs.[9]

Digital clubbing, the presence or absence of splenomegaly and respiratory abnormalities can help point towards leukemia as the underlying disease.

Differential diagnosis

Table 1: Potential etiologies of Roth spots

Subacute bacterial endocarditis





Carbon monoxide poisoning

Prolonged intubation during anesthesia



Diabetic retinopathy

HIV retinopathy

Vitamin B12 deficiency

Complicated labor and traumatic delivery in mothers and neonates

Shaken baby syndrome

Intracranial hemorrhage from arteriovenous malformation or aneurysm

Acute reduction of intraocular pressure following trabeculectomy


Roth spots are generally asymptomatic and typically resolve with treatment of the underlying disease. Treatment should be directed towards underlying process.


  1. Roth M. Uber netzhautuffecstionen bei wundfiebrin. [Retinal manifestations of wound fever.] DeutschA Chir 1872;1:471-84.
  2. 2.0 2.1 2.2 Ling R, James B. White-centred retinal haemorrhages (Roth spots). Postgrad Med J. 1998;74(876):581–582. doi:10.1136/pgmj.74.876.581
  3. Litten M. Ueber akute maligne endocarditis und die dabei vorkommenden retinal veranderungen. Charite-Ann 1878;3:135.
  4. Loughrey PB, Armstrong D, Lockhart CJ. Classical eye signs in bacterial endocarditis. QJM. 2015;108(11):909–910. doi:10.1093/qjmed/hcv055
  5. Mostaghim, Anahita S, et al. “A Retrospective Epidemiologic Study to Define Risk Factors, Microbiology, and Clinical Outcomes of Infective Endocarditis in a Large Tertiary-Care Teaching Hospital.” SAGE Open Medicine, vol. 5, 2017, p. 205031211774177., doi:10.1177/2050312117741772.
  6. Touger M, Gallagher EJ, Tyrell J. Relationship between venous and arterial carboxyhemoglobin levels in patients with suspected carbon monoxide poisoning. Ann Emerg Med. 1995. April;25(4):481–3.
  7. Zehetner C, Bechrakis N. White centered retinal hemorrhages in Vitamin B12 deficiency anemia. Case Rep Ophthalmol. 2011;2:140-144
  8. 8.0 8.1 Veronese C, et al. Multimodal ophthalmic imaging of staphylococcus aureus bacteremia associated with chorioretinitis, endocarditis, and multifocal brain abscesses. Am J of Ophthalmol Case Rep. March 2020; 17:100577
  9. Bernardes Filho F, Machado CC, Queiroz RM, Nery B. Hallmark Cutaneous Signs of Infective Endocarditis The Journal of Emergency Medicine. 2018; 54(6):876-877.