THE EYE IN SYSTEMIC DISEASE

Dr Adejoh.O.M

Three common conditions

• Hypertension
• Diabetes
• Sickle Cell Disease.
• Thyroidopathies.

HYPERTENSIVE RETINOPATHY - Introduction

• Bilateral
• Symmetrical
• Prevalence 4-10%
• Small blood vessel disease
• Caused by systemic hypertension
• Acute or chronic
• Systolic or diastolic
• End organ disease manifestation

Introduction

• Hypertensive Retinopathy (HTR) consists of a spectrum of retinal vascular changes that are pathologically related to both transient and persistent microvascular damage from elevated blood pressure
• HTR occurs in up to 25% of patients with hypertension

General pathology

• Arterioles respond to elevated luminal pressure by vasoconstriction to reduce flow.
• Pathology develops when the increased pressure causes endothelial damage.
• Degeneration of the arteriolar smooth muscle leads to stretching of the endothelium, breaks, and leakage of plasma into the vessel wall.
• Plasma clotting within the vessel wall produces mural thickening and luminal narrowing. This process is called fibrinous necrosis

Pathophysiology 1

• HTR includes two disease processes;
• The acute effects of systemic arterial hypertension are a result of vasospasm to autoregulate perfusion.
• The chronic effects of hypertension are caused by arteriosclerosis and predispose patients to visual loss from vascular occlusions or macroaneurysm.

Pathophysiology 2

• The arteriosclerotic changes of HTR are caused by chronically elevated blood pressure, defined as systolic greater than 140 mmHg and diastolic greater than 90 mmHg.
• Hypertension is usually essential and not secondary to another disease process.

Pathophysiology 3

• However, many young patients with secondary hypertension (e.g. from pheochromocytoma, primary hyperaldosteronism, Cushing’s syndrome) may actually present to an ophthalmologist with bilateral vision loss due to serous macular detachment, bilateral optic disc edema, and exudative retinal detachment.

Pathophysiology 4

• The effects of systemic hypertension on the retinal, optic nerve head and choroidal circulation produce three distinct and independent manifestations:
• (i) hypertensive retinopathy
• (ii) hypertensive optic neuropathy
• (iii) hypertensive choroidopathy.

Pathophysiology 5

• Retinal hemorrhages develop when necrotic vessels bleed into either the nerve fiber layer (flame shaped hemorrhage) or the inner retina (dot blot hemorrhage)
• Cotton wool spots are caused by ischemia to the nerve fiber layer secondary to fibrinous necrosis and luminal narrowing. Ischemia to the nerve fibers leads to decreased axoplasmic flow, nerve swelling, and ultimately fluffy opacification.
• Exudates occur later in the course of disease, surrounding areas of hemorrhage, as a result of lipid accumulation.

Pathophysiology 6

• Papilledema is a result of both leakage and ischemia of arterioles supplying the optic disc that undergo fibrinous necrosis.
• Ischemia causes optic nerve swelling and blurred disc margins, while leakage causes hemorrhage and disc edema

Hypertensive Retinopathy – Classification

• HR grades I and II are typically chronic
• HR grades III and IV are typically acute
• diastolic blood pressure >= 110 correlates with grade III
• diastolic blood pressure >= 130 correlates with grade IV�

Risk factors

• Duration of hypertension
• Race; higher in Africans than Europeans
• Sex; prevalence of HTR is higher in women
• Age
• Systolic blood pressure level; the major risk factor for malignant hypertension is the amount of blood pressure elevation over normal.
• Renal status; In patients with essential hypertension, persistent microalbuminuria is a marker of early end-organ damage including retinopathy

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Hypertensive Retinopathy – Prevalence, Risk factors

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• Family history
• Medications
• Obesity
• Smoking
• Stress
• Alcohol consumption
• Lack of exercise

Symptoms of HTR

• Many patients are asymptomatic
• Blurred vision
• Headache

Signs of HTR

• widening of the arteriole reflex
• constricted and tortuous arterioles
• retinal hemorrhages
• hard exudates
• cotton wool spots
• retinal edema
• arteriovenous crossing signs
• copper or silver wire arterioles (copper or silver colored arteriole light reflex)
• papilledema

Hypertensive Choroidopathy

• Choroidopathy is rare but may occur as the result of an acute hypertensive crisis in young adults
• Elschnig spots are small black spots surrounded by yellow halos which represent focal choroidal infarcts.
• Siegrist streaks are flecks arranged linearly along choroidal vessels indicative of fibrinoid necrosis associated with malignant hypertension
• Exudative retinal detachment, sometimes bilateral, may occur in severe acute hypertension such as that associated with toxaemia of pregnancy.

Hypertensive Optic Neuropathy

• The signs of optic neuropathy include;
• flame shaped hemorrhages at the disc margin
• blurred disc margins
• congested retinal veins
• Papilloedema
• secondary macular exudates.
• Hypertensive optic neuropathy can cause chronic papilledema, leading to optic nerve atrophy and severe loss of visual acuity

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Keith–Wagener–Barker and ‘Simplified Classification’ Systems for Hypertensive Retinopathy

Classification:Keith Wagener Baker (KWB)

AV crossing changes

Papilloedema

Hypertensive Retinopathy – Diagnostic Techniques & Signs

Generalised narrowing of the retinal arterioles

Hypertensive Retinopathy – Diagnostic Techniques & Signs

Focal narrowing of the retinal arterioles –� Copper and Silver Wiring

Hypertensive Retinopathy – Diagnostic Techniques & Signs

Gunn’s sign (nipping) &

right-angled crossing

Bonnet’s sign-distal banking

Hypertensive Retinopathy – Diagnostic Techniques & Signs

Gunn’s sign, right-angled crossing & Bonnet’s sign

Salus’ sign?

Hypertensive Retinopathy – Diagnostic Techniques & Signs

Early malignant

Dot and blot haemorrhages

Hard and soft exudates

Diffuse arteriolar narrowing

Arterio-venous crossing defects

Grade 3 OD

Grade 4

Hypertensive Retinopathy – Diagnostic Techniques & Signs

Advanced malignant

Macular star

Papilloedema

Hypertensive Retinopathy – Classification Grade 4

• Diabetic retinopathy
• Retinal vein occlusion
• Ocular ischaemic syndrome
• Anaemia

Other Ocular Complications of HT

• Central or branch retinal artery occlusion
• Central or branch retinal vein occlusion
• Retinal arterial macroaneurysms.
• Hypertension also leads to more advanced diabetic retinopathy progression.
• Anterior ischaemic optic neuropathy
• Cranial nerve palsies; commonly 3^rd, 4^th, 6^th and 7^th cranial nerves

Hypertensive Retinopathy – Prevalence, Morbidity Risk

• Stroke (7x)
• Heart attack (4x)
• Coronary artery disease (3x)
• Peripheral artery disease (2x)

Treatment

• Routine blood pressure monitoring and treatment will prevent HTR from developing.
• Prompt and accurate diagnosis of HTR, especially when associated with malignant hypertension, is necessary to avoid visual and systemic morbidity.
• Patient education regarding proper diet, exercise, and medication compliance is crucial.

Treatment

• The treatment for malignant hypertension is to reduce the systemic blood pressure below 140/90 mmHg. This can be accomplished by any of the armamentarium of medical treatments for hypertension.
• Medical treatment can only treat the acute changes of hypertension from vasospasm and vascular leakage.
• There is no treatment for arteriosclerotic changes of chronic hypertension.

Prognosis

• Patients with severe HTR and arteriosclerotic changes are at increased risk for coronary disease, peripheral vascular disease, and stroke.
• Since arteriosclerotic changes in the retina do not regress, these patients remain at increased risk for retinal artery occlusions, retinal vein occlusions, and retinal macroaneurysms.

Prognosis 2

• Most retinal changes secondary to malignant hypertension will improve once blood pressure is controlled.
• Damage to the optic nerve and macula, however, could cause long term reductions in visual acuity.

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Hypertensive Retinopathy – Clinical Pearls

Ocular Manifestations of Systemic Diseases

Diabetes and Eye

Introduction

• The International Diabetes Federation estimates that there are 415 million adults living with diabetes worldwide.
• 70% of people with diabetes live in low- and middle-income countries
• Type 2 diabetes accounts for over 90% of all cases.
• The increase in type 2 diabetes is associated with modern-day lifestyles, characterized by unhealthy eating (foods high in sugar, salt and fat), physical inactivity and increasing obesity

Introduction 2

• Diabetes increases the risk of a range of eye diseases, including cataract, but the main cause of blindness associated with diabetes is Diabetic Retinopathy (DR)
• Cataract and DR are the 2^nd and 6^th leading causes of global visual impairment respectively
• DR is a chronic progressive, potentially sight threatening disease of the retinal microvasculature associated with prolonged hyperglycaemia and other conditions linked to DM such as hypertension
• DR usually develops between 10 and 20 years of onset of DM

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Epidemiology of Diabetic Retinopathy

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• The reported prevalence of DR among the diabetic populations has been estimated to be about 40%.
• As the prevalence of diabetes increases, so will the risk of DR.
• By 2030 the number of people likely to go blind from DR would be 3.3 million, 54% more than in 2010
• In Sub Sahara Africa, the proportion will be higher due to inadequate infrastructure and resources to manage the disease.

Diabetes in Nigeria.

• 7.1% of Nigerians have diabetes.
• Only 15% knew they had the condition. (National Blindness survey)
• Omolase in Owo found a prevalence of retinopathy of 15% among adult diabetics.
• (Ashaye et al in Ibadan: 42.1%, hospital based )

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Ocular and Visual Complications of Diabetes Mellitus 1�

• FUNCTIONAL
• Tritan color vision deficiencies
• Refractive error changes
• Accommodative dysfunction
• Visual field defects
• EXTRAOCULAR
• Muscle anomalies
• Mononeuropathies involving third, fourth, or sixth
• Cranial nerves
• Ptosis
• INTRAOCULAR
• Pupillary reflexes: Sluggish pupillary reflexes
• Conjunctiva:
• Bulbar conjunctival microaneurysms
• Tear film: Tear film deficiencies resulting in dry eye syndrome

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Ocular and Visual Complications of Diabetes Mellitus 2�

• Cornea:
• Reduced corneal sensitivity
• Reduced corneal wound-healing ability
• Basement membrane abnormalities resulting in increased frequency of abrasions or recurrent erosion syndrome
• Descemet's membrane wrinkling
• Endothelial cell morphology changes, often resulting in increased corneal thickness
• Iris:
• Depigmentation
• Rubeosis iridis, possibly with associated ectropion uvea and
• peripheral anterior synechiae
• Neovascular glaucoma
• Lens:
• Higher prevalence of cataracts
• Reversible opacities and snowflake cataracts rarely seen in industrialized countries

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Ocular and Visual Complications of Diabetes Mellitus 3

• Vitreous :
• Hemorrhage in proliferative retinopathy
• Retina:
• Non-proliferative retinopathy
• Proliferative retinopathy
• Macula
• Macular Oedema
• Ischaemic maculopathy
• Optic nerve
• Papillopathy
• Ischemic optic neuropathy
• Higher incidence of open-angle glaucoma

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Risk factors for DR

• Long duration of DM; After 20 years of DM, up to 99% of patients with Type 1 DM and 60% of patients with Type 2 DM will have DR
• Poor blood sugar control
• Undiagnosed DM
• Hypertension
• Nephropathy

Risk factors for DR 2

• Pregnancy
• High serum lipids
• Cataract surgery
• Obesity
• Anaemia

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Ocular Anatomy

Pathogenesis of DR

• Diabetes damages all the major cells of the retina
• Exposure to hyperglycemia over an extended period results in biochemical and physiologic changes that ultimately cause endothelial damage.

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Pathogenesis of DR 2

• Mechanisms of cellular damage include
• intracellular sorbitol accumulation
• oxidative stress due to free radical excess, accumulation of advanced glycation end products and excessive activation of several protein kinase C isoforms.
• Disruption of ion channel function is an important early feature.

Pathogenesis of DR 3

• There is increased (↑) production of a number of mediators e.g. Vascular Endothelial Growth Factor (VEGF)
• This results in ↑ blood flow, ↑ capillary permeability, proliferation of the extracellular matrix and thickening of the basal membranes, angiogenesis and tissue remodeling

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Pathogenesis of DR

Pathophysiology:�

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• Loss of Pericytes

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Healthy retinal capillaries

Diabetic capillaries: non-perfused areas

Natural Course of Diabetic Retinopathy

• Retinal capillary microaneurysms are usually the first visible sign of DR
• Increased formation of microaneurysms can lead to excessive vascular permeability of the retinal capillaries, resulting in the development of retinal edema, usually in the macular area
• Obliteration of the retinal capillaries leads to retinal ischaemia
• Endothelial proliferation occurs after ischemia, with the subsequent pre-retinal new vessel proliferation

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Features of DR

• Microaneurysms
• Retinal haemorrhages
• Hard exudates
• Cotton wool spots
• Venous changes
• Arterial changes
• Retinal oedema
• Intraretinal Microvascular Abnormalities (IRMAs)
• Neovascularization

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Microaneurysms

• Microaneurysms are localized out-pouchings, mainly saccular, of the capillary wall that may form either by focal dilatation of the capillary wall where pericytes are absent, or by fusion of two arms of a capillary loop.
• Most develop in the inner capillary plexus (inner nuclear layer) frequently in relation to areas of capillary non-perfusion

Retinal haemorrhages

• Retinal nerve fibre layer haemorrhages arise from the larger superficial pre-capillary arterioles and because of the architecture of the retinal nerve fibres are flame-shaped
• Intraretinal haemorrhages arise from the venous end of capillaries and are located in the compact middle layers of the retina with a resultant red ‘dot/blot’ configuration
• Deeper dark round haemorrhages represent haemorrhagic retinal infarcts and are located within the middle retinal layers

Hard Exudates

• Hard exudates are caused by chronic localized retinal oedema and develop at the junction of normal and oedematous retina.
• They are composed of lipoprotein and lipid-filled macrophages located mainly within the outer plexiform layer

Cotton Wool Spots

• Cotton wool spots are composed of accumulations of neuronal debris within the nerve fibre layer.
• They result from disruption of nerve axons, the swollen ends of which are known as cystoid bodies, seen on light microscopy as globular structures in the nerve fibre layer

Venous Changes

• Venous anomalies seen in ischaemia consist of;
• generalized dilatation and tortuosity
• looping
• beading (focal narrowing and dilatation)
• sausage-like segmentation
• The extent of the retinal area exhibiting venous changes correlates well with the likelihood of developing proliferative disease.

Arterial Changes

• Arterial changes consist of;
• narrowing
• silver-wiring
• obliteration

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Diabetic Macular Oedema (DMO)

• Diabetic maculopathy (foveal oedema, exudates or ischaemia) is the most common cause of visual impairment in diabetic patients, particularly type 2.
• Diffuse retinal oedema is caused by extensive capillary leakage, and localized oedema by focal leakage from microaneurysms and dilated capillary segments.
• The fluid is initially located between the outer plexiform and inner nuclear layers; later it may also involve the inner plexiform and nerve fibre layers, until eventually the entire thickness of the retina becomes oedematous.

Classification of Diabetic Maculopathy

• Focal oedema
• Well-circumscribed retinal thickening associated with complete or incomplete rings of exudates
• Diffuse maculopathy
• Diffuse retinal thickening, which may be associated with cystoid changes. Landmarks are obliterated by severe oedema which may render localization of the fovea impossible
• Ischaemic maculopathy
• Signs are variable and the macula may look relatively normal despite reduced visual acuity.

Clinically significant macular oedema

Hard exudates

within 500 μm

of centre of

fovea with adjacent

oedema which may

be outside 500 μm

limit

Retinal oedema one disc area or larger any

part of which is within one disc diameter

(1500 μm) of centre of fovea

Retinal oedema

within 500 μm

of centre of fovea

Intraretinal Microvascular Anomalies

• Intraretinal microvascular abnormalities (IRMA) are arteriolar-venular shunts that run from retinal arterioles to venules, thus bypassing the capillary bed and are therefore often seen adjacent to areas of marked capillary hypoperfusion

Neovascularization

• Neovascularisation is the hallmark of Proliferative Diabetic Retinopathy (PDR)
• New vessels may proliferate on the optic nerve head (NVD = new vessels at disc) and along major temporal vascular arcades (NVE = new vessels elsewhere)

�International Clinical DR Disease Severity Scale�

�International Clinical Diabetic Macular Oedema Disease Severity Scale�

Advanced Diabetic Eye Disease

• This is a serious vision-threatening complication of DR. Features include
• Preretinal/vitreous haemorrhage
• Tractional Retinal Detachment(RD)
• Rubeosis iridis

CLINICAL CLASSIFICATION OF DIABETIC RETINOPATHY

• Background
• Pre-proliferative
• Proliferative
• End-stage diabetic eye disease

Background

Blot haemorrhage

Exudate

Microaneurism

Diabetic maculopathy

Hard exudate

Pre-proliferative

Vascular tortuosity

Haemorrhage

CWS

Microaneurism

Proliferative retinopathy

NVD

NVE

Laser burn scars

Pre-retinal haemorrhage

Advanced diabetic eye disease

Preretinal fibrosis and tractional retinal detachment

Rubeosis iridis

End-stage diabetic eye disease

• PHTHISIS

Shrunken, soft eye with

opaque vascularised

cornea and no visual

potential

Severe macular oedema

Moderate NPDR

Neovascularization at the disc (NVD)

Vitreous Haemorrhage

PDR with Tractional RD�

Iris Neovascularization

Management of DR

• History;
• Asymptomatic
• loss of vision, may be gradual or sudden
• Detailed ocular examination
• Slit lamp biomicroscopy
• Fundus photography

Retinal Diagnostic Tests

• Optical Coherence Tomography (OCT)
• Fundus Fluorescein Angiography (FFA); this is a diagnostic test used to evaluate the health and blood flow of the retina
• B scan ultrasonography

Optical Coherence Tomography

• Optical Coherence Tomography (OCT); is a non-contact, micron-level, high-resolution diagnostic method that uses infrared light in the 800–840 nm wavelength range to provide real-time non-invasive imaging of the retina. Images acquired correlate well with retinal histology as demonstrated with light microscopy.
• OCT has been routinely used in measuring retinal thickness for the evaluation of macular oedema caused by diseases such as diabetic retinopathy

OCT

Normal scan

Macular oedema

FFA

Normal FFA

New vessels on the disc

Management of DR

• Control Systemic Parameters
• Good blood sugar control with HbA1c level in the 6-7% range
• Good BP control (not more than 130/80mmHg)
• Total cholesterol should be less than 200mg/dl
• Hemoglobin should be above 13g/dl
• No trace of protein should be detected in the urine

Indications for treatment of DR

• Severe NPDR
• PDR
• Severe diabetic macular oedema
• Clinically significant macular oedema

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Treatment options for DR

• Laser photocoagulation
• Intravitreal anti-VEGF injection e.g. Bevacizumab
• Corticosteroids
• Vitrectomy

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Laser Photocoagulation

• It involves directing a high-focused beam of light energy to create a coagulative response in the target tissue
• Laser photocoagulation often temporarily arrests progressive visual loss from DR or diabetic macular oedema but rarely improves it
• May be panretinal, grid or focal

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Laser Photocoagulation 3

• Panretinal laser photocoagulation
• Indicated for PDR, severe NPDR
• Grid/focal laser photocoagulation
• Indicated for diabetic macular oedema

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Laser Photocoagulation

Panretinal laser photocoagulation

Anti-VEGF

• VEGF levels are increased in the vitreous and retina in patients with DR
• Anti-VEGF drugs are used as adjunct therapies to laser treatment, primary treatment for diabetic macular edema and PDR
• Indicated for the treatment of PDR, diabetic macular oedema
• Examples include bevacizumab (Avastin) 1.25mg, ranibizumab (Lucentis) 0.5mg, afflibercept (Eyelea)2mg

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Corticosteroids

• In eyes of patients with DMO, corticosteroids inhibit the expression of VEGF and decrease angiogenesis.
• Platelet-derived growth factor is a proinflammatory cytokine that induces the expression of the VEGF gene, an effect that is downregulated by corticosteroids
• Indicated in the treatment of refractory macular oedema

Vitrectomy

• Indications
• Severe persistent vitreous haemorrhage
• Tractional retinal detachment involving or threatening the macular
• Premacular haemorrhage

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Mechanisms of vision loss in DR

• Macular ischemia
• Macular edema
• Vitreous hemorrhage
• Preretinal haemorrhage
• Epiretinal membrane formation
• Retinal detachment
• Neovascular glaucoma

Recommended Follow-up Schedule

Other ocular complications of DM 1

• Changes in refraction; Hypermetropic shift in hypoglycemia, myopic shift in hyperglycemia and decreased accommodation
• Lids; xanthelasma, recurrent styes
• Cornea; ↓ corneal sensation and ↑ incidence of infective corneal ulcers
• Iris; rubeosis iridis
• Lens; cataract

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Other ocular complications of DM 2

• Retinal vascular occlusions e.g. retinal vein occlusion, retinal artery occlusion
• Optic nerve; anterior ischaemic optic neuropathy, diabetic papillopathy
• Intraocular pressure;↑incidence of primary open angle glaucoma, neovascular glaucoma
• Extraocular muscles; ophthalmoplegia due to�diabetic neuropathy e.g. CN III and VI palsy. Pupil is usually spared in 3^rd CN palsy
• Ocular ischaemic syndrome

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Differential diagnosis of DR

• Retinal vein occlusion
• Retinal vasculitis
• Hypertension
• Ocular ischemic syndrome
• Sickle cell retinopathy.

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Role of the Internist/Endocrinologist

• ALL patients especially over 40 years with diabetes are at risk of CSME/Retinopathy.
• Do not dismiss complaints of reduced visual performance.
• Do Snellen and near visual acuity
• Do dilated funduscopy in ALL diabetic patients.
• Use a professional ophthalmoscope (Keeler)

Role 2

• Look out for signs of Disease in the retina, especially haemorrhage and exudate.
• Maintain High index of suspicion.
• Refer at the earliest.

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Ocular manifestations of Sickle Cell Disease

Definition

• Sickle cell disease is a hemoglobinopathy affecting mostly the negroid race.
• Natural selection occurred in parts of Africa because patients with mild sickle cell disease were very resistant to malaria and survived to reproduce.

Definition ctd

• Several genotypes: AC, SA, SS, SC, & Sthal where A is normal hemoglobin and the others are abnormal variants. Abnormalities are due to improper amino acid substitution.
• SS patients have the worst systemic complications while SC and Sthal patients have the most severe ocular problems. This is because the blood is more viscous in these patients and the small retinal arterioles occlude more easily.

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Introduction

• Sickling haemoglobinopathies are caused by one or more abnormal haemoglobins which induce the red blood cell to adopt an anomalous shape under conditions of hypoxia and acidosis.
• Because these deformed red blood cells are more rigid than healthy cells, they may become impacted in and obstruct small blood vessels.

Introduction 2

• The sickling disorders in which the mutant haemoglobins S and C are inherited as alleles of normal haemoglobin A have important ocular manifestations.
• While many hemoglobinopathies exist, those resulting in proliferative retinopathy are limited to sickle cell disease.

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Introduction 3

• These abnormal haemoglobins may occur in combination with normal haemoglobin A or in association with each other as indicated below;
• SS; The disease is characterized by severe chronic haemolytic anaemia and periodic potentially fatal, crises due to vaso-occlusive disease involving most organs.
• Despite the severity of systemic manifestations ocular complications are usually mild and asymptomatic.�

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Introduction 4

• AS (sickle-cell trait); It is the mildest form and usually requires severe hypoxia or other abnormal conditions to produce sickling.
• SC (sickle-cell C disease);It is characterized by haemolytic anaemia and infarctive crises that are less severe than in SS disease but may be associated with severe retinopathy.
• SThal (sickle-cell thalassaemia); is characterized by mild anaemia but may be associated with severe retinopathy�

Epidemiology

• Sickle cell retinopathy develops in up to 42% of individuals during the second decade of life
• Proliferative sickle cell retinopathy complications are a major contributor to vision loss, leading to visual impairment in 10–20% of affected eyes.
• The frequency of retinopathy is greatest in adulthood, but retinopathy has also been described in children

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Pathophysiology of SCR

• The pathogenesis for SCR is vaso-occlusion that leads to retinal hypoxia, ischemia, infarction, neovascularization, and fibrovascularization.
• In sickle cell anemia, the amino acid substitution valine for glutamate occurs on the beta chain at the sixth position.
• This substitution, combined with conditions that may promote sickling (i.e., acidosis, hypoxia), triggers the deoxygenated Hb S to polymerize, making the erythrocyte rigid. This rigidity is partially responsible for the vaso-occlusion.

Pathophysiology of SCR 2

• Vaso-occlusion is also in part due to the interaction between sickled cells and the vascular endothelium.
• The adherence of sickled cells to the endothelium triggers an inflammatory process with the release of inflammatory agents.
• The activated endothelia are procoagulant, thereby inducing further adherence of sickled cells to the endothelium.

Pathophysiology of SCR 3

• The activated endothelium and rigid sickled cells bind to von Willebrand factor and thrombospondin, which is secreted by activated platelets.
• The result of this cascade is vascular stasis, hemolysis, and vaso-occlusion of the capillary beds.

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• There is a low frequency of visual loss in SCD which may be explained, at least in part, by the high frequency of spontaneous regression (20–60% of cases) through the development of atrophic lesions or autoinfarction.
• Spontaneous regression, which occurs most frequently about 2 years after the development of proliferative SCR, is an important determinant in the natural history of proliferative SCR

Management

• History
• Any personal or family history of sickle cell trait or disease?
• Inquire about painful systemic crises.
• Patients may have visual complaints, varying in nature and intensity.
• Symptoms may range from transient flashes and floaters to sudden profound decrease in vision.
• Detailed ocular examination is essential

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Anterior segment features

• Conjunctival lesions are characterized by isolated dark red vascular anomalies shaped like commas or cork screws. They involve small calibre vessels and are most often located inferiorly.
• Iris lesions consist of circumscribed areas of ischaemic atrophy. Rubeosis may occasionally be seen.��

Posterior segment features

• Retinal manifestations;
• The retinal manifestations of sickle-cell disease can be non-proliferative or proliferative; in the latter case, there is a real risk of ocular morbidity.
• Both non-proliferative and proliferative manifestations are caused by erythrostasis secondary to sickling.

Staging (proliferative) -Goldberg

Stage I

• peripheral arteriolar occlusions
• Stage II
• peripheral arterio-venular anastomoses
• Stage III
• neovascularization
• Stage IV
• vitreous hemorrhage
• Stage V
• retinal detachment

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Staging of proliferative

Sickle-Cell Retinopathy (SCR)

1 - Peripheral arteriolar occlusion

2 - Peripheral arteriovenous anastomoses

3 - Neovascularization (‘sea-fan’)

4 - Vitreous haemorrhage

5 - Fibrovascular proliferation and traction

Non-proliferative retinopathy

• Asymptomatic Lesions
• Venous tortuosity is one of the first ocular signs of sickling and is due to peripheral arteriovenous shunts
• Silver-wiring of arterioles in the peripheral retina which represents previously occluded vessels
• Salmon patches are pink, preretinal or superficial intraretinal haemorrhages at the equator, which lie adjacent to arterioles and usually resolve without sequelae.

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Non-proliferative retinopathy 2

• Black sunbursts are patches of peripheral RPE hyperplasia
• Macular depression sign is an oval depression of the bright central macular reflex due to atrophy and thinning of the sensory retina.
• Peripheral retinal holes and areas of whitening similar to ‘white-without-pressure’ are occasionally seen

Black sunburst and salmon patch

Non-proliferative retinopathy 3

• Symptomatic Lesions
• Macular arteriolar occlusion occurs in about 30% of patients
• Acute central retinal artery occlusion is rare.
• Retinal vein occlusion is uncommon.
• Choroidal vascular occlusion may occasionally be seen, particularly in children
• Angioid streaks (result from crack-like breaks in Bruch's membrane) occur in a minority of patients.�

�sea fan

Peripheral arteriolar occlusion in sickle cell retinopathy

Proliferative retinopathy

‘Sea-fan’ neovascularization

Fibrovascular proliferation

Fibrovascular proliferation

and bleeding

Non-proliferative retinopathy

Salmon patches (equatorial

haemorrhages)

Black sunbursts ( RPE

hyperplasia )

Retinal holes

MULTIPLE SEA FANS

PRERETINAL HEMORRHAGE

Sea fan neovascularization

Treatment of SCR

• Treatment is not required in most cases because new vessels tend to auto-infarct and involute spontaneously without treatment.
• Peripheral laser scatter photocoagulation for neovascularization.
• Occasionally vitreoretinal surgery may be required for tractional retinal detachment and/or persistent vitreous haemorrhage.

Differential diagnosis of SCR

• Proliferative diabetic retinopathy
• Branch retinal vein occlusion
• Ocular ischaemic syndrome
• Retinopathy of prematurity
• Retinal vasculitis

Graves ophthalmopathy

• Other names: thyroid eye disease, thyroid orbitopathy
• Autoimmune inflammatory disorder whose underlying cause continues to be elucidated
• Signs and symptoms may progress and abate independently of other clinical features
• Eye findings may occur even in the absence of objective evidence of thyroid dysfunction (euthyroid Graves disease)

Diagnostic criteria for Graves ophthalmopathy

Key points about Grave’s disease:

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• Most common cause of eyelid retraction

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• Most common cause of bilateral or unilateral proptosis.

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• More common in women

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• Associated with hyperthyroidism in 90% of patients; 6% are euthyroid

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• Smoking is associated with increased risk and severity of ophthalmopathy.

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• The course of ophthalmopathy does not necessarily parallel the activity of the thyroid gland or the treatment of thyroid abnormalities.

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Grave’s disease/Thyroid Ophthalmopathy

Clinical signs

• Eyelid retraction- most common sign
• Lid lag
• Proptosis
• Restrictive extraocular myopathy
• Optic neuropathy

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Treatment:

• Correction of thyroid function abnormality-
• Anti-thyroid drugs
• Radio active iodine
• thyroidectomy
• Orbital decompression- to treat optic neuropathy, orbital congestion, advanced proptosis
• Topical ocular lubricants
• Corticosteroid treatment
• Orbital radiotherapy- targets lymphocytes?

Treatment and Prognosis:

• Self limiting, but….
• may run an active course of exacerbation and remissions
• Therapy directed toward decreasing orbital congestion and inflammation or expanding the bony volume

Treatment and Prognosis:

• Often improves with establishment of euthyroid state, but eye disease may continue to progress
• Elective orbital decompression, strabismus surgery and eyelid retraction repair usually are not considered until ophthalmic signs have been stable for 6-9 months.