MANAGEMENT OF SICKLE CELL RETINOPATHY

WEEKLY CLINICAL MEETING BY DR EJIAKOR IFEOMA

OUTLINE: INTRODUCTION GENETICS/EPIDERMIOLOGY PATHOPHYSIOLOGY OCULAR MANIFESTATION MANAGEMENT CONCLUSION

INTRODUCTION Sickle cell disorder encompasses a group of inherited genetic disorder which causes red blood cell to become sickle and affect multiple organ systems. It is the most common inherited genetic disorder found in blacks. Normal RBC are soft, round and flexible allowing blood to flow easily. In SCD,RBC can change from round to half moon when it is deoxygenated.

 They are hard, inflexible and plug up small blood vessels. This causes the blood and oxygen to be slowed down or stopped which in turn leads to multiple organ damage. Alteration in the sequence of amino acid affects the shape, solubility ,oxygen affinity and life span of the hb molecule.

GENETICS &EPIDERMIOLOGY Sickle cell disorder results from a mutant gene in the sequence of amino acids in the chain of adult haemoglobin. Haemoglobulin is composed of 2 and 2(HbA) chains located on xsome 16 and 11 respectively. Abnormal red blood cells include; Haemoglobulin S; substitution of valine for glutamic acid at position 6 of the chain.

 Sickle cell disease (SS);It is a homozygous recessive disease. Most common and each HbS gene is inherited from both parents who are carriers. Ocular complications are usually mild and asymptomatic but causes severe haemolytic anaemia. Haemoglobin C; substitution of lysine for glutamic amino acid in 6th position. Sickle cell(SC);2nd most common form. Results from inheritance of 1 HbS gene and HbC gene. Associated with milder systemic manifestations but more serious ocular complications

 Haemoglobin thal: abnormality due to defective production(in quantity)of chain.0(no chain present),+(reduced chain). Sickle cell thalessemia;3rd most common. Patient inherits a sickle cell gene and a thal gene. Sickle cell trait(AS);It is the mildest form and requires severe hypoxia or abnormal conditions to produce sickling.

 If both parents are carriers, for each pregnancy, their is a 75% chance of each offspring will not have an SS gene(50%AS,25%AA).The frequency is the same for each pregnancy.

 Nigeria 25% have the AS and 3-10% (black Americans) SS prevalence Nigeria 2%(SS)Black American,0.4% SC Nigeria 0.6% (6% southwest) Black American,0.2%,Ghana 25% HbC also affects the Middle East, Indian subcontinent while S Thal is more in the Mediterranean countries. Nigeria has the largest pool of sickle cell in the World. The overall ocular complication in SCD is unknown, however PSR occurs in about 40% of SC and 20% of SS.

PATHOPHYSIOLOGY Under deoxygenated conditions, HbS undergoes marked decrease in solubility, increased viscosity and polymer formation that stiffens the erythrocyte. After recurrent episodes of sickling, membrane damage occurs and the cells are no longer capable of resuming a biconcave shape upon reoxygenation. thus they become irreversibly sickled cells(ISC).

 Hypoxia aids adhesion of sickled cell to the vascular endothelium . The result of this cascade is vascular stasis, haemolysis, and vasoocclusion of the capillary beds and this exacerbates ischemia. There is a inverse paradoxical r/ship between severity of systemic disease and severity of SCR.

 Reasons; Viscosity theory decrease blood viscosity may protect against vascular occlusion HbC&Hbthalhaemotocritviscosity occlusion

Ischemia versus infarction theory; SS; Retinal occlusion (complete) will lead to infarction necrosis SC/S Thal ; less complete vascular occlusion will lead to ischeamiaVEGFneovascularization Sickle cell (HbSS) rbc are more efficiently removed by RES than SC ,thereby increased abnormal cells causing sickling and incomplete occlusion in the end vessels in the eyes.

OCULAR MANIFESTATIONS The ocular manifestation include both anterior and segment. ANTERIOR SEGMENT ADNEXAE Ptosis (due to vasoocclusion of the blood supply to the nerves involved) Upper lid swelling(due to Sickle cell crisis) EXTRAOCULAR MUSCLE Palsy CONJUCTIVA Pallor Jaundice Conjuctival Injection

 Dilated linear vessels, tortuous small calibre vessels Corkscrew(comma shaped vessels more inferiorly) ANTERIOR CHAMBER mild flare (due to compromised integrity of the vessel wall) IRIS 1. sectoral atrophy at the pupillary margins, 2. rubeosis irides which causes spontaneous hyphaema. 3. Hyphaema from blunt trauma/surgery.

 The environment in the Ac promotes HBS polymerization and impairs out flow of aqueous due to blockage of TM by sickle cells increase IOP Orbital compression syndrome(rare complication) due to vaso-occlusive crises in the orbital bones. Presents with acute pain/peri-orbital swelling +/- proptosis, EOM palsy, visual impairment.

POSTERIOR SEGMENT 4 major categories, optic disc changes, maculpathy, nonproliferative and proliferative retinal changes. SCR occurs more in the periphery. Vitreous; Haemorrhage secondary neovascularisation. Optic disc; transient dark red spots which represents plugs of sickle rbc within the superficial capillaries. More common in SS. Optic atrophy

Acute/chronic maculopathy Acute due to acute vascular occlusion of the retina. May infrequently lead to ischemia infarction Results to complete loss of vision/central/paracentral scotoma. Chronic maculopathy is commoner. Seen in 30% SC. Macular depression sign; is an oval depression of the bright central macular reflex due to atrophy and thinning .

 Macular hole are rare. Predisposing factors are 1. Traction on the macular from neovascularisation in the periphery and on the disc 2. Vaso-occlusive events in the macula, local ischemia, infarction, thinning, atrophy hole.

NON-PROLIFERATIVE RETINOPATHY Venous tortuosity is due to perfusionAV shunts. Salmon Patch(orange-red)due to abrupt occlusion and rupture of the arteriole. ischemic necrosis weakening of the wallhaemorrhage. Bright red but changes it colour due to degenerated rbc . Schisis cavity ; caused by the resolution which result in a area of atrophic split retina. Iridescents spots : glistening refractile deposits in the cavity(hemosiderin-laden macrophages).

 Black sunburst are patches of peripheral RPE hyperplasia (pigmented chorioretinal scar ) .It develops around a previous haemorrhage. Appear ovoid measuring 1.5-2 disc diameter with stellate/spiculate borders. Angioid streaks occur in 40yrs in SCD Epiretinal membrane may produce visual loss in SCD.

PROLIFERATIVE RETINOPATHY It is characterised by neovascularisation from repeated episode of ischemia secondary to repetitive peripheral arteriolar occlusion.

 It is the most severe ocular change in SCD. It is progressive. GOLDBERG CLASSIFICATION(1971) Stage 1 Peripheral microvascular occlusions.

FA shows area of avascular & abnormal capillary bed from abnormal perfused retina. Stage 2 Av anastomosis due to shunting of blood from occluded arterioles to the nearest venules.

 FA does not show leaking vessels Stage 3 Neovascularisation due to repeated ischemic event in the non perfused area .In the early stage, NV fronds are small &flat on the retinal surface with time & they grow in size &establish the characteristic appearance Sea Fan neovascularisation. risk of vitreous haemorrhage/RD. They can autoinfarct(20%-60%) after 2yrs which leads to fibrovascular formation. FA show leaking vessels.

Stage 4;Vitreous haemorrhage The neovascular tufts may continue to proliferate and bleed into the vitreous. May be the first presentation of SCD in SC. Spontaneous or trauma induced May be limited with floaters or dense with sudden loss of vision. May resolve or persist with yellowish vitreous membrane. Tends to recur

 Stage 5;Retinal detachment(rhegmatogenous or tractional). End stage of PSR Retinal atrophy-------RD Ischemia, thinning, hole formation -----RD

MANAGEMENT Patient may present with any of the mentioned ocular manifestation(reduced vision, loss of vision, ptosis, eyelid swelling, hyphaema, floaters, flashes of light) P/medical history to rule out previous painful crises, jaundice, anaemia, blood transfusion Family history is important to rule out sickle cell trait/disease

Ocular Examination Check VA, IOP,Slit lamp examination; AC( hyphema),iris for atrophy and rubeosis iridis, vitreous(floaters),dilated fundoscopy (BIO),B/Scan ultrasound, Fluorescein Angiography, Fundus photography. Other investigations include, FBC, Genotype, Electrophoresis Blood film

DIFFERENTIAL DIAGNOSIS Hypertensive retinopathy Diabetic retinopathy Hyperviscosity syndrome Retinal vascular obstruction(BRVO,CRVO,) Eales disease

TREATMENT Aim is to preserve or restore vision(heamatologist & internal medicine) General Measures Rehydration Treat infections Multivitamins preparation(SIkLAVIT) Blood transfusion(packed cells)

Treatment of PSR is aimed at ablating or inducing regression of the sea fan. Various modalities have been utilized, including diathermy, cryotherapy, xenon arc photocoagulation, and various techniques of laser photocoagulation, such as feeder vessel, local scatter, and peripheral circumferential scatter. Laser photocoagulation is the treatment modality most commonly used.

Vitreoretinal surgery may be indicated for the ff; tractional or rhegmatogenous retinal detachments, nonclearing vitreous hemorrhages, visually disabling epiretinal membranes. NOTE;HYPHAEMA is am emergency in SCD. should be managed aggressively tend to have a poorer prognosis with the same degree of hyphema than patients without sickle cell disease.

 predisposed to optic nerve damage and/or central retinal artery occlusion with mild increases in IOP. All black patients with hyphema, even those without a past history of sickle cell disease or trait, should be tested for the disease or trait. Rebleeding is a potentially devastating complication,(2-6 days) after the initial bleed. The chance of rebleeding has been reported as high as 64%. Maintain an IOP lower than 25 mm Hg.

Managaement Bed rest with the head elevated. Topical beta-adrenergic antagonists are the mainstay of therapy for IOP control. Oral steroids, topical steroids, and/or aminocaproic acid (Amicar) all reduce the incidence of rebleeds. Avoid topical epinephrine, whenever possible, because it causes vasoconstriction and exacerbates the sickling process. If possible, avoid miotic agents that may increase inflammation. Avoid hyperosmotic agents because they may increase hemoconcentration and viscosity.

 Avoid carbonic anhydrase inhibitors that may lead to hemoconcentration, systemic acidosis, and an elevated level of ascorbic acid; they may cause further sickling. Methazolamide is preferable, Paracentesis or anterior chamber washout is advised for increased IOP.

PATIENTS EDUCATION Patients with sickle cell disease should be well informed of their current and potential longterm complications. Encourage patients to enrol at a local or regional sickle cell clinic. Provide patients with information regarding a local support group Prompt treatment of identified cases Genetic counseling.

CONCLUSION Sickle cell disease is an important cause of morbidity and mortality in childhood. Ocular manifestation can be severe and sudden blindness may result amidst other complications. SCR is increasingly being recognised as a cause of significant ocular morbidity and blindness in Africa. An early screening and management programme for retinal disease would reduce complications and optimize visual efficiency .

IRIS ATROPHY

IRIDESECENT DEPOSITS IN SCHISIS CAVITY

Black sunburst B. Elevated sea fan neovascularization with white fibroglial mantle. C. Untreated sea fan with localized and diffuse vitreous haemorrhage