Anemia-Associated Fundus Hemorrhage

Key points of this disease

• Fundus hemorrhage due to anemia (anemic retinopathy) is a condition in which systemic anemia causes bilateral retinal hemorrhages.
• According to WHO definition, anemia is defined as Hb ≤ 13 g/dL (adult male) or Hb ≤ 12 g/dL (adult female).
• In many cases, it is asymptomatic and discovered when an eye examination is requested during treatment of a systemic disease.
• Fundus findings are characterized by bilateral blot-shaped and round hemorrhages predominantly in the posterior pole, and Roth spots may be observed.
• No ophthalmic treatment is required; the main treatment is medical management of the underlying disease (e.g., aplastic anemia, leukemia, iron deficiency anemia).
• When anemia improves, retinal hemorrhages gradually resolve over several months.

1. What is fundus hemorrhage due to anemia?

Fundus hemorrhage due to anemia (anemic retinopathy) is a condition in which systemic anemia causes bilateral retinal hemorrhages.

In anemic retinopathy, anemia is confirmed on blood tests. According to the WHO definition, anemia is defined as hemoglobin (Hb) concentration ≤ 13 g/dL in adult males and ≤ 12 g/dL in adult females, and hematocrit (Ht) ≤ 39% in adult males and ≤ 36% in adult females.

WHO diagnostic criteria for anemia

Hemoglobin (Hb) concentration

Adult male: 13 g/dL or less

Adult female: 12 g/dL or less

Hematocrit (Ht) value

Adult male: 39% or less

Adult female: 36% or less

Epidemiology and Prevalence

Regarding the prevalence of anemic retinopathy, a cross-sectional study by Carraro et al. reported that retinopathy was observed in approximately 28.3% of patients with anemia or thrombocytopenia¹. In many cases, it is discovered when an ophthalmologic examination is requested during treatment for systemic anemia. It often lacks subjective symptoms and is mainly found incidentally.

The main causative diseases include the following:

• Aplastic anemia
• Sickle cell disease
• Leukemia (acute and chronic)
• Multiple myeloma
• Macroglobulinemia (also involves increased blood viscosity)
• Iron deficiency anemia (severe cases)

In these diseases, in addition to anemia, thrombocytopenia and coagulation abnormalities are often present, further exacerbating the bleeding tendency.

Q Does anemia always cause retinal hemorrhage?

A

Mild anemia rarely causes retinal hemorrhage. Severe anemia (especially when hemoglobin is markedly decreased) or blood diseases accompanied by thrombocytopenia and coagulation abnormalities (such as leukemia and aplastic anemia) are more likely to cause retinal hemorrhage. To assess the severity of anemia and the presence of retinal changes, regular eye examinations combined with blood tests are important.

2. Main Symptoms and Clinical Findings

Subjective Symptoms

Anemic retinopathy is often asymptomatic. It is frequently discovered when an ophthalmic examination is requested during treatment for a systemic disease.

However, subjective symptoms may appear in the following situations:

• Visual field abnormalities: Noticed when bleeding occurs in the macula.
• Decreased visual acuity: Occurs when bleeding extends to the fovea or when retinal edema develops.

Subjective Symptoms

Asymptomatic (in most cases): Mainly incidental findings. Discovered when an eye examination is recommended during treatment for a systemic disease.

Visual field abnormalities: When bleeding occurs in the macula, visual field abnormalities are noticed.

Decreased visual acuity: Occurs when bleeding extends to the fovea or when retinal edema develops.

Fundus Findings

Predominantly posterior pole, bilateral retinal hemorrhages: Spotty, round, or oval hemorrhages of various sizes are scattered.

Roth spots: Hemorrhages with a white center. Characteristically seen in severe anemia.

Pallor of the optic disc and retina: Observed in cases of severe anemia.

Details of Clinical Findings

Detected by fundus examination or fundus photography. Scattered blot-shaped, round, or oval hemorrhages of various sizes are seen bilaterally in the entire retina, mainly in the posterior pole. The depth of hemorrhage also varies; most are intraretinal, but subretinal and preretinal hemorrhages may also occur.

Typical findings include pallor of the retina and optic disc, retinal hemorrhages, Roth spots, hard exudates, soft exudates, narrowing of retinal arteries, and venous dilation and tortuosity. Compared to diabetic retinopathy, lesions are more concentrated in the posterior pole.

Roth spots are hemorrhages with a white center, appearing not only in severe anemia but also in infective endocarditis and leukemia. The white center is thought to be a leukocyte aggregate or fibrin clot.

Q What are Roth spots?

A

Roth spots are retinal hemorrhages with a white center. They are characteristically seen in three diseases: infective endocarditis, severe anemia, and leukemia. The white center is thought to be a leukocyte aggregate or fibrin clot. In infective endocarditis, septic emboli are the mechanism; in anemia and leukemia, vascular wall disruption or thrombocytopenia is involved. The presence of Roth spots suggests a systemic severe disease, so a systemic workup is necessary when they are found.

3. Causes and Risk Factors

Main Causative Diseases

The causative diseases of anemic retinopathy are diverse.

Bone marrow production disorders

• Aplastic anemia: Decreased hematopoietic function of the bone marrow. Often accompanied by thrombocytopenia, worsening bleeding tendency.

Hematologic malignancies

• Leukemia (acute myeloid, acute lymphoblastic, chronic myeloid, chronic lymphocytic): Production of abnormal blood cells along with thrombocytopenia, increasing bleeding tendency.
• Multiple myeloma: Both anemia and increased blood viscosity cause fundus changes.

Hemolytic anemia

• Sickle cell disease: Obstruction of microvessels by deformed red blood cells also causes fundus changes.

Increased blood viscosity

• Macroglobulinemia (Waldenström disease): Increased blood viscosity due to abnormal proteins damages retinal vessels.

Deficiency anemia

• Severe iron deficiency anemia: Mild anemia rarely causes fundus hemorrhage, but it can appear in severe anemia.

Pathophysiology

Reduced oxygen supply to retinal tissue due to anemia is thought to cause vascular wall breakdown.

• Hypoxemia → Fragility of retinal capillary walls → Hemorrhage
• Thrombocytopenia (e.g., leukemia) → Impaired hemostasis → Increased bleeding tendency
• Increased blood viscosity (multiple myeloma, macroglobulinemia) → Impaired retinal vascular perfusion

4. Diagnosis and Examination Methods

Diagnosis of anemic retinopathy requires both confirmation of anemia by blood tests and confirmation of retinal hemorrhage by fundus examination.

Diagnostic process

1. Blood tests (systemic evaluation)

• Hb level: adult male <13 g/dL, adult female <12 g/dL (WHO criteria)
• Ht level: adult male <39%, adult female <36% (WHO criteria)
• CBC (complete blood count): evaluation of anemia severity, type, and platelet count
• Reticulocyte count and peripheral blood smear: differential diagnosis of anemia causes

2. Fundus examination and fundus photography (first-line)

• Confirmation of bilateral, posterior pole-predominant retinal hemorrhages
• Confirmation of blot, round, or oval hemorrhage patterns
• Presence or absence of Roth spots
• Pallor of the retina and optic disc
• Changes in retinal arteries and veins (arterial narrowing, venous dilation)

3. Other tests

• OCT: useful for layer-specific evaluation of macular edema and retinal hemorrhage (especially when vision is affected)
• Bone marrow examination and hematologic workup: confirmation of underlying disease

Differential diagnosis

It is important to differentiate from bilateral diseases that cause retinal hemorrhage.

Disease	Main findings	Key points for differentiation
Anemic retinopathy	Blot-shaped/round hemorrhages, posterior pole predominance, Roth spots	Decreased Hb on blood test
Diabetic retinopathy	Hemorrhages with cotton-wool spots and hard exudates	Many findings other than hemorrhage (spots)
Hypertensive retinopathy	Primarily linear hemorrhages	Linear hemorrhages predominant over blot-shaped ones
Infective endocarditis	Roth spots	Systemic symptoms such as fever and heart murmur
Leukemic retinopathy	Differentiated by definitive diagnosis of leukemia	Blood test, bone marrow examination

Diabetic retinopathy often shows findings other than hemorrhage, such as cotton-wool spots and hard exudates. Hypertensive retinopathy can be differentiated because it mainly presents with linear hemorrhages rather than blot hemorrhages.

Q Is OCT examination necessary?

A

Fundus examination is the basic method, but OCT is useful when hemorrhage extends to the macula and affects visual acuity. OCT can evaluate the depth of retinal hemorrhage (intraretinal, subretinal, preretinal) and the degree of macular edema. In clinical practice, it is used when there is decreased vision.

5. Standard Treatment

Treatment Policy

There is no effective ophthalmic treatment for fundus hemorrhage associated with anemia. Medical treatment for the underlying anemia is important.

Key Points of Treatment

Treatment of fundus hemorrhage associated with anemia is primarily managed by internal medicine, not ophthalmology.

• It is most important to identify the underlying cause of anemia and initiate appropriate treatment accordingly.
• When anemia improves, retinal hemorrhage gradually resolves.
• Explain to the patient that resolution may take several months.

Medical Treatment According to Underlying Disease

Iron deficiency anemia

• Oral iron preparations (ferrous sulfate, sodium ferrous citrate, etc.)
• Management of the cause of anemia (e.g., gastrointestinal bleeding, menorrhagia)

Aplastic anemia

• Immunosuppressive therapy (antithymocyte globulin + cyclosporine)
• Hematopoietic stem cell transplantation (severe cases, young patients)
• Blood transfusion therapy (symptom control)

Leukemia

• Chemotherapy (varies by acute/chronic type)
• Molecular targeted therapy (e.g., imatinib for CML)
• Hematopoietic stem cell transplantation

Multiple myeloma

• Chemotherapy including proteasome inhibitors (e.g., bortezomib)

Sickle cell disease

• Blood transfusion therapy / Hydroxyurea therapy
• Hematopoietic stem cell transplantation (some cases)

Follow-up observation

The effect of medical treatment is monitored by fundus examination. As anemia improves, retinal hemorrhages gradually resolve. Resolution may take several months. If there is macular hemorrhage, the course of hemorrhage resolution and visual recovery is regularly checked.

Role of ophthalmology

The ophthalmologist has the following roles:

• Initial fundus evaluation: Record the location, extent, and depth of hemorrhage. Check for the presence of Roth spots, hard exudates, and soft exudates.
• Visual acuity and visual field testing: Evaluate the impact of macular lesions on visual function.
• Regular follow-up: Confirm the effect of anemia treatment by fundus findings and track the resolution of hemorrhage.
• Collaboration with internal medicine/hematology: When fundus hemorrhage is severe (especially with preretinal hemorrhage or vitreous hemorrhage), it is important to provide information to and collaborate with the hematology department.
• Indications for emergency ophthalmic intervention: There is no ophthalmic treatment for anemic retinopathy itself, but if there is massive preretinal hemorrhage covering the macula and a significant impact on visual function, individual management should be considered.

Q Are eye drops or injection treatments necessary in ophthalmology?

A

There is no effective ophthalmic treatment (eye drops, injections, laser, etc.) for anemic retinopathy. Since there is no direct treatment for fundus hemorrhage, medical treatment of the underlying anemia is the only management approach. Ophthalmology plays a role in observing the course of hemorrhage through regular fundus examinations and evaluating the degree of visual impairment due to macular hemorrhage.

6. Characteristics of fundus findings by blood disease

Aplastic anemia

In aplastic anemia, anemia due to decreased red blood cells and bleeding tendency due to thrombocytopenia overlap. Jiang et al. reported a pediatric case with multilayered severe retinal hemorrhage and serous retinal detachment, indicating that it can progress to retinal atrophy and edema, a serious complication². The following findings are observed in the fundus:

• Various bleeding patterns: In addition to blot and round hemorrhages, large flame-shaped hemorrhages and preretinal hemorrhages due to thrombocytopenia may occur.
• Roth spots: In severe cases, multiple hemorrhages with white centers may appear.
• Bilateral involvement: Typically, hemorrhages of similar severity are seen in both eyes.

Leukemia

In leukemia, normal hematopoiesis in the bone marrow is impaired, and the combination of anemia, thrombocytopenia, and coagulation abnormalities markedly increases the bleeding tendency.

• Leukemic retinopathy: In addition to hypoxic changes due to anemia, infiltration of abnormal blood cells (blasts) may occlude blood vessels.
• Retinal infiltration: Abnormal cells may infiltrate around retinal blood vessels, forming white lesions.
• Severity of retinal hemorrhage: When thrombocytopenia is severe (e.g., platelet count <20,000/μL), hemorrhages tend to be multiple and massive.

Sickle Cell Disease

In sickle cell disease (SCD), sickled red blood cells cause occlusion within retinal blood vessels.

• Preproliferative and proliferative sickle cell retinopathy: Ischemia-induced retinal neovascularization may occur, progressing to vitreous hemorrhage and tractional retinal detachment.
• Simple findings: Characteristic findings include “salmon patch” hemorrhages and “refractile deposits.”
• Overlap with anemic retinopathy: General hemorrhagic findings due to anemia may overlap with ischemic findings due to vascular occlusion.

Multiple Myeloma and Macroglobulinemia

In these diseases, increased blood viscosity due to abnormal proteins (hyperviscosity syndrome) is the main cause of retinal changes.

• Venous dilation and tortuosity: Venous stasis due to high-viscosity blood.
• Hemorrhage and soft exudates: Ischemic changes due to impaired blood flow.
• Central retinal vein occlusion-like findings: In severe cases, findings similar to central retinal vein occlusion may be observed.

7. Classification of Retinal Hemorrhage by Morphology and Depth

In anemic retinopathy, hemorrhages occur in multiple layers of the retina. The morphology of the hemorrhage reflects the depth of the retinal layer affected and is also useful for prognosis.

Classification by Depth of Hemorrhage

Intraretinal hemorrhage (multilayered)

• Nerve fiber layer hemorrhage (flame-shaped hemorrhage): Flame- or fan-shaped hemorrhage along the course of nerve fibers. Occurs in the most superficial layer of the retina.
• Inner retinal layer hemorrhage (dot- or round-shaped hemorrhage): Round hemorrhage from capillaries, accumulating between the inner and outer granular layers.
• Sub-internal limiting membrane hemorrhage (berry-shaped hemorrhage): Blood accumulates between the internal limiting membrane and the nerve fiber layer, presenting a dome shape with smooth borders.

Preretinal hemorrhage (subhyaloid hemorrhage)

• Blood accumulates between the retina and the vitreous (subhyaloid space).
• Due to gravity, red blood cells settle and form a fluid level (horizontal level), characteristic of a “boat-shaped hemorrhage.”
• If large, it may cover the macula and significantly affect vision.

Subretinal hemorrhage

• Blood accumulates between the photoreceptor layer and the RPE.
• It appears as a dark red lesion with indistinct borders.
• When it occurs in the macula, it can significantly affect vision.

Main hemorrhage patterns in anemic retinopathy

Throughout the retina, mainly in the posterior pole, bilaterally, blot-shaped, round, or oval hemorrhages of various sizes are scattered. The depth of hemorrhage also varies; most are intraretinal, but subretinal and preretinal hemorrhages may also be seen.

Roth spots are hemorrhagic spots with a white center, thought to be formed by leukocyte aggregation or fibrin clot in the center of an intraretinal hemorrhage.

8. Pathophysiology and detailed pathogenesis (internal mechanisms)

Vascular damage due to hypoxemia

Reduced oxygen supply to retinal tissue due to anemia causes breakdown of the vessel wall. Red blood cells are responsible for oxygen transport, and this capacity is reduced in anemia.

1. Formation of hypoxic state: Decreased Hb → reduced oxygen-carrying capacity of blood → insufficient oxygen supply to tissues
2. Endothelial damage: Chronic hypoxia → endothelial cell damage and weakening of retinal capillary walls
3. Increased vascular permeability: Breakdown of vessel wall → hemorrhage and edema
4. Compensatory vasodilation: Retinal vessels dilate as compensation for hypoxia → venous dilation and tortuosity

Exacerbation of bleeding tendency due to thrombocytopenia

In leukemia and aplastic anemia, in addition to anemia, thrombocytopenia significantly exacerbates bleeding tendency. Since normal hemostatic mechanisms do not function, bleeding easily occurs even with minor vascular wall damage.

Relationship between severity of anemia and fundus changes

There is a certain relationship between the severity of anemia and the appearance of fundus changes. In the analysis by Venkatesh et al., Hb < 8.95 g/dL was identified as a threshold for predicting anemic retinopathy with a sensitivity of 85.8% and specificity of 68.9% ³. In the study by Carraro et al., the frequency of fundus changes markedly increased when Hb < 8 g/dL, and in severe cases with both anemia and thrombocytopenia (< 50 × 10⁹/L), retinal hemorrhage was observed in almost all cases ¹. That is, fundus changes are unlikely to appear in mild anemia, but hemorrhage occurs at a high rate in severe anemia or cases with thrombocytopenia.

Pathophysiology of Roth spots

Recent histological studies have revealed that the white center of Roth spots consists of fibrin-platelet aggregates and accumulation of inflammatory cells ⁴⁵. Previously thought to be bacterial emboli or leukocyte aggregates, it is now considered a non-specific finding that appears in various microvascular disorders such as anemia, leukemia, diabetes, and SLE, and is not specific to infective endocarditis ⁴. In anemia and leukemia, it is thought that platelets and fibrin accumulate at the site of capillary endothelial disruption, forming a white center.

9. Ophthalmic management of systemic diseases associated with anemic retinopathy

Ophthalmic management of aplastic anemia

Aplastic anemia is a severe hematologic disease in which the hematopoietic function of the bone marrow is reduced. Fundus hemorrhage occurs due to both thrombocytopenia and anemia.

Key points for fundus management:

• Massive fundus hemorrhage is likely to occur when the platelet count is less than 20,000/μL.
• After hematopoietic stem cell transplantation, infectious endophthalmitis and ocular surface disorders due to graft-versus-host disease (GVHD) may occur due to the effects of immunosuppressive drugs.
• GVHD-related dry eye is an important complication after transplantation.

Ophthalmic management of leukemia and malignant lymphoma

In hematologic malignancies, in addition to retinal hemorrhages, intraocular infiltration of tumor cells may occur.

Characteristics of leukemic retinopathy:

• Leukemic cells may infiltrate around retinal blood vessels, forming white lesions.
• Hemorrhages due to anemia and thrombocytopenia are mixed with those caused by leukemic cell infiltration.
• Retinal hemorrhages may temporarily worsen after initiation of chemotherapy (due to platelet consumption from rapid cell breakdown after treatment starts).

Differential diagnosis of intraocular infiltration:

• Intraocular infiltration is relatively common in acute leukemia (especially ALL).
• When leukemic cells infiltrate the vitreous, findings may resemble vitritis.
• If central nervous system infiltration is confirmed by lumbar puncture or bone marrow examination, the risk of intraocular infiltration is also high.

Ophthalmic management of hyperviscosity syndrome

In multiple myeloma and macroglobulinemia (Waldenström disease), blood hyperviscosity due to abnormal proteins (M proteins) is the main pathology.

Characteristics of hyperviscosity retinopathy:

• Marked dilation and tortuosity of retinal veins are characteristic.
• Uneven venous dilation called “sausage sign” may be observed.
• Differentiation from central retinal vein occlusion may be necessary.
• Improvement in blood viscosity (via plasma exchange or treatment of the underlying disease) leads to improvement in fundus findings.

10. Precautions in Ophthalmic Practice

Collaboration with Hematology/Internal Medicine

It is essential to always keep in mind that anemic retinopathy is an ocular manifestation of systemic blood disorders. Close collaboration with hematology and internal medicine is important.

• Information sharing at initial consultation: Communicate the extent of retinal hemorrhage, presence of Roth spots, and impact on visual acuity to the hematology department.
• Confirmation of treatment priority: Explain to the patient and family that treatment of the blood disorder takes top priority.
• Fundus management during chemotherapy: During chemotherapy for leukemia or lymphoma, the risk of infectious endophthalmitis due to immunosuppression increases, so ophthalmic monitoring may be necessary.
• Evaluation of transfusion/platelet transfusion effects: In severe thrombocytopenia (platelet count <20,000/μL) with extensive retinal hemorrhage, evaluating fundus changes after transfusion or platelet transfusion may be useful.

Key Points for Patient Explanation

• Carefully explain that “even if there is retinal hemorrhage, active ophthalmic treatment is not possible.”
• Convey the outlook that “if the anemia (underlying disease) is cured, the retinal hemorrhage will also resolve spontaneously,” to alleviate patient anxiety.
• Inform in advance that “it may take several months for complete resolution.”
• If there is macular hemorrhage, explain that “recovery of vision may take time.”
• Advise that “if you experience decreased vision or new changes in your vision, please seek medical attention promptly.”

11. Course and Prognosis

Factors Affecting Prognosis

• Successful treatment of the underlying disease: The most important factor. Retinal hemorrhages gradually resolve when anemia improves.
• Location of hemorrhage: If macular hemorrhage is present, vision loss may persist.
• Extent of hemorrhage: Preretinal hemorrhage (subhyaloid hemorrhage) may take a long time to resolve.

Resolution of Fundus Hemorrhage

When anemia improves, retinal hemorrhages gradually resolve. It takes several months for them to disappear.

• Small dot or blot hemorrhages: Resolve relatively early (weeks to months).
• Large preretinal or vitreous hemorrhages: May take several months or longer to resolve.
• Vision after macular hemorrhage: Even after hemorrhage resolves, if RPE damage persists, vision may not fully recover.

Q How long does it take for fundus hemorrhage to disappear?

A

Assuming anemia improves, retinal hemorrhages gradually resolve over several months. Small hemorrhages often disappear relatively early, but large hemorrhages or preretinal hemorrhages take longer. If macular hemorrhage involves the fovea, vision may not fully recover even after the hemorrhage resolves. Regular fundus examinations are important to monitor the resolution of hemorrhage.

12. References

1. Carraro MC, Rossetti L, Gerli GC. Prevalence of retinopathy in patients with anemia or thrombocytopenia. European Journal of Haematology. 2001;67(4):238-244. PMID: 11860445. DOI: 10.1034/j.1600-0609.2001.00539.x

   • 226例の貧血・血小板減少患者を解析した横断研究。網膜症は全体の28.3%に認められ、Hb＜8 g/dLまたは血小板＜50×10⁹/Lで頻度が顕著に増加した。両者を合併する重症例ではほぼ全例に網膜出血を認めたとし、貧血患者全例に眼底検査を推奨している。

2. Venkatesh R, Reddy NG, Jayadev C, Chhablani J. Determinants for Anemic Retinopathy. Beyoglu Eye Journal. 2023;8(2):116-121. PMID: 37521879. DOI: 10.14744/bej.2023.05658

   • 貧血網膜症（AR）の発症因子を解析した研究。Hb＜8.95 g/dLが感度85.8%・特異度68.9%でARを予測する閾値であることを示した。Hb・Ht値の低下が独立した発症リスクであり、貧血患者の眼底スクリーニングの根拠となる。

3. Gurnani B, Tivakaran VS. Roth Spots. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025. PMID: 29494053. Bookshelf ID: NBK482446.

   • Roth斑の最新総説。白色中心はフィブリン・血小板凝集塊と炎症細胞の集積であり、感染性心内膜炎に特異的ではなく、白血病・貧血・糖尿病・SLEなど多様な微小血管障害でも出現する非特異的所見であることを明確にしている。

4. Ling R, James B. White-centred retinal haemorrhages (Roth spots). Postgraduate Medical Journal. 1998;74(876):581-582. PMID: 10211348. DOI: 10.1136/pgmj.74.876.581

   • Roth斑の組織学・病態を整理した総説。白色中心は細菌膿瘍ではなく非特異的所見であり、貧血・白血病を含む多様な疾患で生じうることを示し、Roth斑発見時の全身精査の重要性を提起している。

5. Jiang X, Shen M, Liang L, Rosenfeld PJ, Lu F. Severe retinal hemorrhages at various levels with a serous retinal detachment in a pediatric patient with aplastic anemia—A case report. Frontiers in Medicine (Lausanne). 2023;10:1051089. PMID: 36744127. DOI: 10.3389/fmed.2023.1051089

   • 再生不良性貧血の小児例で、貧血と血小板減少が重なって多層性の重症網膜出血と漿液性網膜剥離を来した症例報告。網膜萎縮・浮腫まで進展しうる重篤な合併症であることを示し、血液疾患患者の眼科的フォローの必要性を強調している。

Footnotes

1. Carraro MC, et al. Eur J Haematol. 2001. PMID: 11860445 ↩ ↩²

2. Jiang X, et al. Front Med. 2023. PMID: 36744127 ↩

3. Venkatesh R, et al. Beyoglu Eye J. 2023. PMID: 37521879 ↩

4. Gurnani B, Tivakaran VS. StatPearls. 2025. PMID: 29494053 ↩ ↩²

5. Ling R, James B. Postgrad Med J. 1998. PMID: 10211348 ↩