SEMINAR OF CONGENITAL MACULAR DYSTROPHYES AND RETINOBLASTOMA AND DIABETIC RETINOPATHY. DONE BY Mohammad AL-Hammdan

1. SEMINAR OF CONGENITAL MACULAR DYSTROPHYES AND RETINOBLASTOMA AND DIABETIC RETINOPATHY. DONE BY Mohammad AL-Hammdan

2. Inherited retinal dystrophies and photoreceptor dystrophies Retinitis pigmentosa : (Retinal appearance) Is an inherited disorder of the photoreceptors which has several genotypic and phenotypic varieties. It may occur in isolation or in association with a number of other systemic diseases. PORGERSSIVE DEGENERATON OF RETINA , RODS more than cons PORGERSSIVE DEGENERATON OF RETINA , RODS more than cons

3. PATHOGENESIS The disease affects both types of photoreceptors but the rods are particularly affected. The inheritance may be: •autosomal recessive (sporadic cases are often in this category) •autosomal dominant •X-linked recessive. Several forms of retinitis pigmentosa have been shown to be due to mutations in the gene for rhodopsin. EPIDEMIOLOGY The prevalence of this group of diseases is 1 in 4000. Mimic RP trauma , retinal detachment surg, syphilis rubella , previous occlusion of ret artery or vein , chloropromazineMimic RP trauma , retinal detachment surg, syphilis rubella , previous occlusion of ret artery or vein , chloropromazine

4. SYMPTOMS The age of onset, progression and prognosis is dependent on the mode of inheritance. In general the dominant form is of later onset and milder degree recessive and X-linked recessive forms may present in infancy or childhood. Patients notice poor night vision (nyctalopia), visual fields become increasingly constricted and central vision may ultimately be lost.

5. SIGNS The three signs of typical retinitis pigmentosa are: peripheral clumps of retinal pigmentation termed (bone-spicule pigmentation) attenuation of the retinal arterioles disc pallor. Patients may also have cataracts (glare) at an early age and may develop cystoid macular oedema.

6. The clinical appearance of the peripheral retina in retinitis pigmentosa.

7. INVESTIGATION A careful family history will help to determine the mode of inheritance. The diagnosis can usually be made clinically. Electrophysiologic tests are also useful in diagnosis, particularly in early disease where there may be few clinical signs. Recent work on mapping the genetic loci for the condition has opened new avenues for genetic counselling and determining disease mechanism. The possibility of associated syndromes should be borne in mind. Usher’s syndrome, for example, is a recessive disorder characterized by deafness and retinitis pigmentosa. Retinitis pigmentosa also occurs in mitochondrial disease.

8. MANAGEMENT Unfortunately nothing can be done to prevent the progression of the disease. Associated ocular problems can be treated. Cataracts can be removed and macular oedema may respond to treatment with acetazolamide. Low vision aids may be helpful for a period. The possibility of genetic counselling should be discussed with the patient.

9. PROGNOSIS X-linked recessive and autosomal recessive disease produce the most severe visual symptoms. About 50% of all patients with retinitis pigmentosa will have an acuity of less than 6/60 by the time they reach 50.

10. Cone dystrophy This is less common than retinitis pigmentosa. It is usually autosomal dominant but many cases are sporadic. Patients present in the first decade of life with poor vision. Examination reveals an abnormal, banded macular appearance which has been likened to a bull’s-eye target. No treatment is possible but it is important to provide appropriate help not only to help maximize vision but also to help with educational problems. Genetic counselling should be offered.

11. RETINAL TUMOURS This is the commonest malignant tumour of the eye in childhood with a frequency of 1 per 20000 births. It may be inherited as an autosomal dominant condition but most cases are sporadic. These may be caused either by germinal mutations which can be passed on to the next generation or by somatic mutations (the majority, some 66% of cases) in a single retinal cell which cannot be genetically transmitted.

12. Cont… The retinoblastoma gene has been located and the gene product is thought to control the differentiation of the retinal cell. The disease occurs when the individual has a homozygous defect in the retinoblastoma gene. ch13 In inherited retinoblastoma one gene error is inherited and the other occurs by spontaneous somatic mutation in the retina during development. The mutation rate for the gene is thought to be 1:10000000, and 100 000 000 divisions are needed to form the adult retina thus the chance of a somatic mutation occurring in a subject with only one functioning gene is very high. The homozygous state is thus achieved by a ‘double hit’ event and the condition behaves as a pseudodominant disorder. Although it occurs frequently in affected families there may be some skip generations. Theoretically the disease should behave in a recessive fashion as only one functioning gene is required to control retinal cell differentiation.

14. HISTORY AND SYMPTOMS The child may present (at a mean age of 8 months if inherited and 25 months if sporadic) with: •A white pupillary reflex (leukocoria) due to a pale elevated tumour at the posterior pole of the eye. Sometimes the tumour is bilateral on Presentation. •A squint due to reduced vision.Occasionally, a painful red eye. Most cases present by the age of two. Inherited retinoblastoma is often bilateral.When the condition is unilateral on presentation and there is no family history, inherited disease is less likely, but not excluded.

15. SIGNS Dilated fundoscopy shows a whitish pink mass protruding from the retina into the vitreous cavity. INVESTIGATIONS The diagnosis is usually a clinical one. Cerebrospinal fluid and bone marrow must be examined to check for metastatic disease.

16. TREATMENT Removal (enucleation) of the eye is performed in advanced cases.Radiotherapy can be used in less advanced disease as can cryotherapy and photocoagulation. Metastatic disease (either by direct spread through the optic nerve or by a haematogenous route) is treated with chemotherapy. Regular follow-up of an affected child is required and of subsequent offspring. Genetic counselling should be offered and children whose parents have had a retinoblastoma should be assessed from infancy.

17. PROGNOSIS This depends on the extent of the disease at diagnosis. Overall the mortality of the condition is 15%. Tumor confined to the globe –survival rate of over 90% at 3 yrs. Unfortunately some 50% of children with the germinal mutation will develop a second primary tumor (e.g. an osteosarcoma of the femur) or a tumour related to treatment with radiotherapy.

18. Retinal vascular disease

19. SIGNS OF RETINAL VASCULAR DISEASE The signs of retinal vascular disease result from two changes to the retinal capillary circulation: • leakage from the microcirculation; • occlusion of the microcirculation.

20. Leakage from the microcirculation This results in: • haemorrhages caused by leakage of blood from damaged vessels; • oedema of the retina, the result of fluid leakage from damaged vessels; • exudates formed by lipids, lipoprotein and lipid containing macrophages.These are yellow in colour, with well-defined margins.

21. Occlusion of the microcirculation This results in: •Cotton wool spots (previously termed soft exudates).These are caused by a build-up of axonal debris in the nerve fibre layer of the retina. This results from a hold-up in axoplasmic transport due to ischaemia. Cotton wool spots are found at the margins of ischaemic infarcts. Their visibility depends on nerve fibre layer thickness so that they are seen close to the optic disc, where the nerve fibre layer is thick, and not in the periphery where the nerve fibre layer is thin.They are white in colour with indistinct borders. •New vessels. An ischaemic retina releases vasogenic factors (e.g.VEGF) which result in the growth of abnormal blood vessels and fibrous tissue onto the retinal surface and forward into the vitreous. These intravitreal vessels are much more permeable than normal retinal vessels, and their abnormal position predisposes them to break and bleed.