White centered retinal hemorrhages, also known as Roth spots, were first described by Moritz Roth, a Swiss physician in 1872. However, it was not until 1878 that this condition was assigned the name "Roth spot" by Moritz Litten. Litten reported that these white-centered retinal hemorrhages had been detected in 80% of cases associated with subacute bacterial endocarditis. Roth spots are most commonly associated with infective endocarditis. However, they can be seen in a wide variety of medical conditions including leukemia, anemia, hypertensive retinopathy, pre-eclampsia, diabetic retinopathy, and anoxia.
Historically, Roth spots were considered to be a pathognomonic finding for bacterial endocarditis secondary to septic emboli within the retina. Given recent histological data, it is now believed that Roth spots are the result of retinal capillary rupture and intraretinal hemorrhage. Roth spots occur in a multitude of disease processes in which retinal blood vessel injury and subsequent bleeding and hemorrhage occur. A common thread found in these conditions 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 a fibrin-platelet plug at the site of vessel rupture.
White centered retinal hemorrhages are a nonspecific ophthalmologic finding seen in multiple systemic conditions of various etiologies. Roth spots are seen on fundoscopic examination and tend to be located in the peripheral or posterior poles of the eyes. Retinal endothelial dysfunction appears to be a common thread among the diverse causes of white centered retinal hemorrhage. The differential diagnosis of Roth spots is vast and includes:
While multiple theories have been proposed to explain the pathogenesis of white centered retinal hemorrhages, the most widely accepted is that of retinal capillary rupture and intraretinal hemorrhage. Retinal capillary rupture occurs as a result of endothelial cell dysfunction. Extravasation of red blood cells follows vessel rupture with subsequent activation of the clotting cascade and formation of a platelet-fibrin plug at the site of the damaged endothelium. Histological studies revealed the whites lesions are composed primarily of platelet-fibrin thrombi.
Retinal hemorrhage is commonly seen in patients with underlying disease processes that predispose to retinal endothelial dysfunction and rupture. Roth spots may be seen on a routine ophthalmologic exam in asymptomatic patients prompting further diagnosis and evaluation. However, patients may also present with signs and symptoms of systemic illness and retinal hemorrhages noted during acute evaluation. The presence of Roth spots on physical examination should prompt the physician to evaluate for an underlying systemic disease. The clinician should take a thorough history and complete a careful physical exam.
A detailed history with a full review of the system can help to narrow the differential diagnosis and identify the underlying disease process. Attention must be paid to symptoms associated with the more common etiologies of Roth spots. Symptoms of endocarditis and infection including fever, chills and night sweats must be reviewed. Symptoms commonly seen in hematologic disease should also be assessed such as unexplained weight loss, fatigue, abnormal bleeding or bruising and shortness of breath. Review of personal past medical history, as well as family history, may also be helpful in determining the etiology.
Roth spots are seen on fundoscopic examination. A complete ophthalmologic examination should be performed as other retinal abnormalities may accompany Roth spots. After Roth spots are identified, the physician must carefully examine the patient to assess for physical signs of systemic illness. It is important to note the patient's vital signs, particularly blood pressure, temperature, and pulse. Several etiologies of white-centered retinal hemorrhages have classical physical examination findings associated with them; therefore, the physician must have a high index of suspension during the examination. In patients that present with concerns for endocarditis and Roth spots, the clinician must carefully examine for other stigmata of endocarditis including Janeway lesions, Osler nodes, splinter hemorrhages, petechiae and cardiac murmurs. Assessment of digital clubbing, the presence or absence of splenomegaly and respiratory abnormalities is also helpful.
The initial evaluation is based largely on results of a thorough history and physical examination. A complete blood count with differential to assess for leukocytosis, anemia, and thrombocytopenia along with other hematologic abnormalities should be completed in all patients. A fasting plasma glucose or hemoglobin A1C to assess for diabetes mellitus should be performed. If infectious etiology is suspected erythrocyte sedimentation rate, C-reactive protein and blood cultures may be indicated. A transthoracic echocardiogram is an important initial diagnostic test if endocarditis is suspected. Additional tests such as HIV antibody testing, imaging studies or peripheral blood smear should be considered if indicated based on presenting symptoms and physical examination findings.
Roth spots are most often asymptomatic and detected during a routine dilated eye examination. Visual disturbance due to Roth spots is rare but can occur with macular involvement. The majority of white centered retinal hemorrhages will resolve without intervention. Treatment is aimed at the underlying cause and is often supportive. The most important management consideration in patients with Roth spots is the identification of the causative etiology to prevent possible ocular and systemic complications that may occur due to the underlying disease. Follow-up with an ophthalmologist is an important consideration in patients in whom Roth spots are discovered during acute illness. 
When the opthalmologist makes a diagnosis of roth spots, the patient should be referred to other relevant specialists for work up because there are many causes. The initial referral should be to the primary care physician, nurse practitioner and the internist. The evaluation is based largely on results of a thorough history and physical examination. A complete blood count with differential to assess for leukocytosis, anemia, and thrombocytopenia along with other hematologic abnormalities should be completed in all patients. A fasting plasma glucose or hemoglobin A1C to assess for diabetes mellitus should be performed. If infectious etiology is suspected erythrocyte sedimentation rate, C-reactive protein and blood cultures may be indicated. A cardiologist should perform a transthoracic echocardiogram to rule out endocarditis. The infectious disease expert should conduct HIV antibody testing, imaging studies or peripheral blood smear, if indicated based on presenting symptoms and physical examination findings.
|||Wang L,Petrak M,Holz FG,Müller A,Krohne TU, Retinal Hemorrhages in Shaken Baby Syndrome. The Journal of pediatrics. 2019 Apr; [PubMed PMID: 30922497]|
|||Ścisłowicz A,Piejko P,Nowak M,Renke P,Chaniecki P,Rucka A, [Infective endocarditis in a patient with vision disorders]. Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego. 2018 Nov 28; [PubMed PMID: 30531670]|
|||Sabrane I,Belkhadir K,Saoudi S,Benchekroun S,El Ikhloufi M,Cherkaoui O, [Roth spots suggestive of myeloid leukemia: Case report]. Journal francais d'ophtalmologie. 2018 Nov; [PubMed PMID: 30458927]|
|||Zhang J,Chen Y,Yu Z,Liu L, Bilateral Hemorrhagic Retinopathy with Roth Spots in Pediatric-Onset Systemic Lupus Erythematosus and Associated Thrombocytopenia: A Case Report and Review of Literature. Ocular immunology and inflammation. 2018; [PubMed PMID: 29020480]|
|||Lin AL,Burnham JM,Pang V,Idowu O,Iyer S, OCULAR MANIFESTATIONS OF PRIMARY MYELOFIBROSIS. Retinal cases [PubMed PMID: 26836259]|
|||Furtado JM,Toscano M,Castro V,Rodrigues MW, Roth Spots in Ocular Toxoplasmosis. Ocular immunology and inflammation. 2016 Oct; [PubMed PMID: 26472315]|
|||Singh R,Singh SP,Mittal SK,Rana SK, Roth Spots in Chronic Myeloid Leukaemia. The Journal of the Association of Physicians of India. 2014 Sep; [PubMed PMID: 26259322]|
|||Dell'Arti L,Barteselli G,Pinna V,Invernizzi A,Mapelli C,Viola F, Sudden occurrence of Roth spots and retinal hemorrhages following endoscopic adhesiolysis: an SD-OCT evaluation. European journal of ophthalmology. 2015 Dec 1; [PubMed PMID: 26428215]|
|||Mahroo OA,Graham EM, Images in clinical medicine. Roth spots in infective endocarditis. The New England journal of medicine. 2014 Jun 19; [PubMed PMID: 24941198]|