Ординатура / Офтальмология / Английские материалы / Pediatric Opthalmology_Mukherjee_2005

The retinal arteries divided and re-divide to be reduced to arterioles which are end arteries, ultimately to form capillary network. There are two such networks. The first is at the level of nerve fibre layer and the second deeper at the level of outer plexiform layer and inner nuclear layer. There are connecting channels joining the two layers of capillaries.

All the blood vessels are controlled by autonomic nerve system except the retinal system.15

The blood retinal barrier13,14

The permeability of retinal blood vessels differ from vessels of other organs-

1.There is a selective exchange of fluid with protein molecule from retinal capillaries to retinal cells.

2.The retinal capillaries consist of a single layer of non fenestrated endothelium cells that does not allow passage of fluorescein in normal vessels.

3.The retinal blood vessels are without internal elastic lamina and a continuous layer of smooth muscles.

4.A basal lamina covers the outer surface of the vessels.

The blood retinal barrier is a physiological barrier meant to optimise fluid passage into the retinal cells. Only a few metabolic products can pass this barrier from outside.

The barrier is two layered. Tight junction between the pigment epithelium cells forms the outer barrier. The inner is due to tight junction of endothelial cells in retinal capillaries.

Retinal veins

The retinal veins have the same name as retinal arteries. The retinal veins start on the periphery and end in the central retinal vein that leaves the optic nerve 12 mm behind the globe, in more angular fashion than the central retinal artery. Thus the central retinal vein has a longer course in the inter vaginal space than retinal artery. This makes it more exposed to pressure changes in the inter vaginal space. The retinal veins have larger diameter than the arteries in a ratio of 3:2. The arteries and veins share a common sheath, generally the artery crosses over the vein. The veins drain the retina in quadrants. The central retinal vein generally drains directly into cavernous sinus. It also partly drain in superior ophthalmic vein, rarely it drains in inferior ophthalmic vein.

Development of retina16

The retina except the blood vessels is neuro ectodermal in origin. It’s development becomes obvious from very early stage before even the closure of the neural tube i.e. 2 mm stage and continues to develop (macula) after birth. It develops from the optic cup. The two layers of the optic cup are involved in development of the retina. The outer layer gives rise to a single layer of retinal pigment epithelium (RPE). The remaining layers that form the sensory retina develop from the inner layer of the optic cup. A potential space is left in between the two layers throughout the life and when distended causes separation of sensory retina from RPE.

Development of retinal pigment epithelium

The cells of the external walls of the optic cup become pigmented. Its posterior part actually form the pigment epithelium of the retina. The anterior part continues forward to form the anterior pigment layer of iris and ciliary body16.

Development of sensory (pars optica) retina

To begin with, the inner layer of the optic cup is a single layer of epithelium. It divides further to give rise to nine layers of retina which can be grouped broadly in following three groups:

1.The cells that give rise to rods and cones;

2.The cells that give rise to bipolar cells, ganglion cells and supporting tissue.

3.Cells that form ganglion cells axons and nerve fibre layer.

Stages of development of retina16,16A

Stage I—Development of outer nuclear zone and non nucleated marginal zone.

Stage II—Differentiation into inner non nucleated zone and inward migration of the outer nuclear zone.

Stage III—Development of inner neuroblast and outer neuroblast—The ganglion cells, Muller’s fibres and amacrine cells develop from the inner neuroblast. The outer neuroblast gives rise to horizontal cells, nuclei of rods and cones. From the Muller’s fibres develop the two limiting membranes, from the ganglion cells develop the nerve fibre layer.

Stage IV—This is the final stage of organisation of all nine layers.

Development of macula

Development of macula differs from development of rest of the retina. All the layers of adult retina are well formed by fifth month of intra uterine life. Vascularisation of inner retinal layers is complete by eighth month. The macula starts developing very early stage of embryogenesis and progresses fast only to be slowed down and then continues to grow several months post natal. The differentiation of macula is fast up to first three months after which there is sluggish differentiation of central area. The rest of the retina continues to be differentiated and grow. This retardation continues up to eighth month. Then the differentiation continues like rest of the retina. At six months of life the macular area is thicker than rest of the retina. By seventh to eighth month the macula starts thinning due to shift of ganglion cells towards the periphery. At birth the ganglion cells at fovea are reduced to single layer.

Congenital anomalies of retina

Congenital anomalies are numerous and present variable clinical features. They may be symptomless or may cause profound visual loss. They may be obvious at birth, may start at or before birth but manifest late. They can be uniocular or bilateral. They may be present in retina only or may be associated with congenital anomalies of choroid or optic nerve. Anomalies of retinal vessels are very common. As development of vitreous is clearly associated with that of retina, congenital vitreo retinal lesions are common. The congenital anomalies of retina and vitreous have frequent hereditary background, however, sporadic cases are also known.

It is difficult to classify congenital anomalies of retina and vitreous due to their clinical diversity.

They can be classified in following groups:

1.Ophthalmoscopic appearance. They include coloboma, opaque nerve fibre, Bergmeister papillae, macular anomalies, anomalies of blood vessels, anomalies of pigmentation, albinism, retinal detachment, retinal folds, hamartomas.

2.Physiological (visual). Diminished night vision, diminished day vision, abnormal colour vision.

3.Anatomical. This is most probably best suited classification.

The anatomical classification may be :

1. Congenital anomalies of the retina

(a) Anomalies of structures arising from outer layer of the optic cup.

(b) Anomalies of the structures arising from the inner layer of the retina (i) Anomalies of the retinal periphery

(ii) Anomalies of the macula

2.Congenital anomalies of retinal vessels

3.Congenital anomalies of optic nerve

4.Congenital anomalies of vitreous

5.Combined vitreo retinal anomalies

Anomalies of structures arising from outer layer of the retina

The only retinal layer that arises from the outer wall of the optic cup is retinal pigment epithelium. The congenital anomalies of this layer are fewer than those of sensory retina. The anomalies mostly lead to pigmentary disturbance. Commonest anomaly is embryopathic pigmentary retinopathy and localised congenital pigmentation of the retina.

Congenital embryopathic pigmentary retinopathy

This is secondary to intrauterine infection by syphilis, rubella and influenza in the first trimester. The condition is bilateral without any symptoms. The retina is studded with bluish black pigmented dots. The appearance is called salt pepper fundus. The appearance lasts life long. The condition is confused with retinitis pigmentosa. There are no vascular changes. There may be associated optic atrophy. No treatment is required.

Other major anomaly of pigmentation is albinism.

Albinism18

Albinism is a common congenital disorder of metabolism of amino acid tyrosine. The condition has world-wide distribution, the incidence is as high as 1:20,000. However it is reported to be more among coloured races. This may be due to the fact that change in colour of hair, skin and eyes are more visible in dark person than in blonds. Both the sexes are affected equally. Women are the carriers in x linked ocular albinism where they show some features of albinism. Albinism can be either an autosomal recessive or an autosomal dominant trait. It has been observed that sometimes when both the parents have some traits of albinism, they have normal children, this happens when one of the parents is tyrosinase negative and the other is tyrosinase positive. (See page 236)

Clinically albinism can belong to any of the following:

1.Cutaneous albinism

2.Oculo cutaneous albinism

3.Ocular albinism

4.Albinism associated with systemic syndromes.

Whatever may be the clinical presentation, the basic pathology is failure to form melanin, the pigment that is responsible for colour of the skin and hair19. The melanin is formed in a special type of cells called melanocytes which are derived from neural crest. The formation of melanin involves a chemical reaction involving amino acid, tyrosine and enzyme tyrosinase. The melanocytes form melanosomes, which are packed with granules that contain the pigment melanin. The melanin is formed from tyrosine that is converted to tyrosinase, which in turn is converted to dihydro phenylalaline and to quinone.

Cutaneous albinism

The skin is hypo-pigmented in patches. The patches may be congenital or may develop later. The patches may involve the skin of the lids, lashes or eyebrow without any ocular defect.

Oculo cutaneous albinism

This is the commonest type of albinism met with. Clinically there are two types20 of oculo cutaneous albinism:

1.Tyrosinase positive oculo cutaneous albinism

2.Tyrosinase negative oculo cutaneous albinism

The difference is made out by hair bulb incubation test. The test consists of incubation of plucked hair bulb in tyrosine solution. In case of tyrosinase positive albinism, the hair bulb becomes dark. Tyrosinase negative shows more clinical features than positive group.

The ocular features of oculo cutaneous albinism consist of

The skin of the lids is white so are the eyebrows and lashes. The conjunctiva looks hyperaemic. The cornea and AC are normal. The iris is light coloured, devoid of any pigment and transmits reflected ray. The pupil is of normal size and reaction, the colour of the pupil is pink in contrast to a black pupil of a normal child.

The eyes may have squint due to errors of refraction. Horizontal nystagmus is almost constant feature.

Vision is poor. Myopia is more common than hypermetropia. Myopia is frequently associated with high astigmatism. Near vision is normal but the child may not be able to read due to nystagmus. To counteract the nystagmus and use the null zone to maximum benefit, the child develops a head tilt, may have head nodding.

Colour vision is fairly good. There is no night blindness. The child is more comfortable in dim light. In bright light the child has photophobia and glare.

On fundus examination the retinal vessels and choroidal vessels stand out prominently against the white sclera. The retinal pigment epithelium has granules similar to melanin but no pigments. The macula is hypo plastic. The optic nerve head can not be differentiated, its position is denoted by the convergence of the retinal arteries. All types of oculo cutaneous albinism show some type of abnormal crossing of nerve fibres at the chiasma.20

Less common ocular findings are—Paresis of extra ocular muscles, corneal opacity, partial aniridia, persistent pupillary membrane, developmental cataract, hypo plasia of retina.

The common systemic findings consist of pale white skin, which is sensitive to the sun light. The body hair is as white as lashes and eyebrows.

Less common extra ocular features are—Deafness, mental retardation, and coagulation defect. These features are seen in children associated with syndromes involving multiple systems.

Syndromes associated with oculo cutaneous albinism -

Chediak-Higashi syndrome

This is a serious, often fatal condition with multi systemic involvement. Chief among them is chronic lymphadenopathy, lymphomas, mental retardation, hepatospleenomegaly besides oculo cutaneous albinism. The condition is autosomal recessive. The causes of death is recurrent infection and lymphoid infiltration.

Ocular findings

Usual findings of oculo cutaneous albinism are i.e. Bilateral corneal opacity, developmental cataract, there may be disc edema due to lymphoid infiltration.

Waardenburg’s syndrome

There is partial albinism, localised in some places. The systemic manifestations are more than ocular feature. The systemic findings include - Hearing defect, vestibular dysfunction, epilepsy, and a white forelock.

The ocular findings are:

Fused eyebrows which may be white, poliosis of lashes, long lashes, wide inter canthal distance, lateral displacement of puncta, frequent chronic dacryocystitis, pseudo or real squint, blue iris, heterochromia of iris.

Cuteneous albinism—The skin shows patches of hypo-pigmentation with or without involvement of skin of the lid. It should be differentiated from other causes of vitiligo and poliosis.

Ocular albinism—The pigmentary deficiency is exclusively seen in the eyes. Externally the eye looks normal because the iris has normal pigmentation. The pupil is not as pink as in oculo cutaneous albinism but the hypo-pigmented retina may give a pale reflex. Nystagmus is common. The retina is devoid of pigmentation that may be generalised or localised. Women carriers may have less findings in the fundus.

Management

There is no specific treatment for any type of albinism. The treatment is directed to correct error of refraction, give dark glasses, correct amblyopia as far as possible. Instruct the child to use full sleeves and full pants, use broad brimmed hat to protect the skin from sunrays. Some children may require rehabilitation or low vision aids.

Anomalies of structures arising from inner layer of optic cup can be21

1.Dysplasia and a plasia of retina

2.Retinal folds

3.Retinal cysts

4.Retinal detachment

5.Retinos chisis

6.Retinal dystrophy

7.Retinal degeneration

Retinal dysplasia

Retinal dysplasia represents a group of congenital conditions that are due to faculty differentiation of retinal premordium. It can be of two types:

1. Congenital rosette formation and 2. Congenital gliosis.

Congenital rosette formation can be seen in microphthalmic eye or otherwise normal eye. The rosettes are formed when development of neural element overshoots its normal limits. The number of rosettes in an eye may vary from single to multiple. They may be associated with folds in non pigmented epithelium of the ciliary body. The rosettes may be seen anywhere on the retina as masses that may be embedded in the retina, may protrude in the vitreous. On histopathology the appearance is similar to retinoblastoma with central lumen. In fact sometimes they are mistaken as retinoblastoma.

Retinal gliosis

There is proliferation of glial tissue in excess of normal limit. The proliferated glial tissue may be mistaken as intraocular tumour.

Retinal folds

They are caused due to proliferation of inner layer of optic vesicle. Sometimes persistent primary hyper plastic vitreous may cause a traction fold where features of persistent primary hyper plastic vitreous may overshadow the whole picture. Sometimes the folds may span between the optic disc and ciliary body. The common site being inferior temporal retina. Large congenital retinal folds may give a white reflex in pupillary area.

Retinal cysts

Sometimes retinal dysplasia or microphthalmia may be associated with retinal cyst. Peripheral retinal cysts may be asymptomatic and discovered only on routine indirect ophthalmoscopy. They are presumed to be precursors of retinal dialysis or retinoschisis.

Congenital retinal detachment

Congenital retinal detachment takes place when the two layers of the optic cup fail to come in intimate proximity due to unequal rate of growth of the two layers. It is generally seen on the periphery. It may be caused by intrauterine inflammation, is common in microphthalmic eyes.

Congenital retinoschisis

Retinos chisis is a condition where there is a split in the sensory retina, in contrast to a split between sensory retina and retinal pigment epithelium in retinal detachment which is far more common than retinoschisis. In retinoschisis the split is at the level of outer plexiform layer. Congenital retinoschisis is a familial condition. The inheritance is variable. It effects both boys and girls. It is present at birth but diagnosed late either during routine examination or the child presents with diminished vision or squint. A late stage of congenital retinoschisis is termed as juvenile or idiopathic retinoschisis.

The condition is generally bilateral and symmetric. The inner layer is raised, dome like area of elevated sensory retina. It may have a hole in the inner table. However presence of a full thickness hole will cause rhegmatogenous retinal detachment.

Congenital retinal degeneration and dystrophies

Almost all degeneration/dystrophies are congenital in nature, may be present at birth but diagnosed later. They are bilateral and almost symmetrical most of the times. Commonest symptoms being diminished night vision with constricted peripheral field. For details (See page 434.)

Congenital functional defects of vision due to anomalies of retina are:

1.Congenital night blindness

2.Congenital day blindness

3.Congenital colour blindness

Congenital night blindness

This is a rare condition that runs in families with variable inheritance. The striking features are:

1.Absence of signs of hypovitaminosis A, which is otherwise commonest cause of diminished night vision in children in developing countries.

2.Normal ophthalmoscopic appearance

The central vision remains normal in contrast to retinitis pigmentosa which is commonest cause of non reversible night blindness in older children where central vision may be effected. Diminished vision in congenital night blindness is attributed to associated myopia. The colour vision is normal. Night blindness is stationary and permanent. The fields are normal, may have subnormal ERG and EOG.

Differential diagnosis consists of xerophthalmia in developing countries that responds to administration of vitamin A and other causes of diminished night blindness i.e. retinitis pigmentosa and its variations.

Congenital day blindness

This is even rarer than congenital night blindness. There is better vision in dim light. The colour vision is also defective. The eyes are generally amblyopic. There may be some mental retardation. The cases are generally passed as amblyopia. The condition is hereditary.

Congenital colour blindness

Except for a few acquired conditions, all colour defects are congenital in origin with strong family history and variable inheritance.

Congenital anomalies of retinal vessels

Congenital anomalies of retinal vessels are common. They may be in the form of—Division of arteries, their course, tortuosity, capillary malformation, cilio retinal vessel and telangiectasia.

Generally the central retinal artery bifurcates into superior and inferior branches at the optic nerve head. As a congenital anomaly the bifurcation can be in the orbit. The superior and inferior division may trifurcate instead of bifurcation. Abnormal tortuosity is more frequent.

It may be primary anomaly without any clinical significance or may be part of some other vascular malformation. Telangiectasia is seen in Wyburn-Mason syndrome, Sturge Weber syndrome, Coats disease. Angioma formation is characteristics of von Hippel-Lindau disease.

Cilio retinal artery

It is seen in about 15% to 20% eyes as a small twig arising from the temporal border of the optic disc and supplying the retina between the macula and the disc though it is called cilio retinal artery and supply the retina, it is in fact part of ciliary circulation. It arises from the ophthalmic artery. It is occasionally seen in both eyes. It is more common in hypermetropic eyes22. The clinical significance of this anomaly is that the macular blood supply is partly sustained in case of central retinal artery block.

Congenital anomaly of retinal vessels of late onset

There are few conditions of congenital and hereditary origin that manifest late with profound loss of vision. The main pathology in such cases is not presence of congenital anomaly itself but associated endothelial defect that cause escape of exudate, blood or both from the incompetent endothelial lining of abnormal vessels24 causing superficial and deep exudates and haemorrhage. Formation of vitreous bands and circinate retinopathy is common. In all cases with past evidence of exudation, the retinal periphery should be examined with indirect ophthalmoscope and fluorescein angiography. Most of the cases are bilateral and simultaneous but not always symmetric. One eye may be involved more than the other.

The common condition seen in pediatric age group are:

1.Retinal telangiectasis (Coats disease)

2.Retinal angiomatosis (von Hippel-Lindau disease)

3.Retinal cavernous hemanioma disease (see chapter on retinoblastoma)

4.Arterio venous aneurysm (Racemose aneurysm).

Coats disease (Primary/Congenital retinal telangiectasis)25,26

The condition is also known as Lebers miliary aneurysm. (see chapter on retinoblastoma).

It is an exudative retinal vasculopathy that can be seen on any part of the retina but peripheral lesions are more. The temporal retina is most commonly involved. Both the arteries and veins are involved. The condition is non hereditary, boys are affected more than girls in a ratio of 80 : 20. In 80% of cases the condition is unilateral. However the other eye should always be examined for evidence of peripheral lesion because such lesions may be managed better than the original eye, which may be in advanced stage of disease and difficult to treat.

Though most of the children with Coat’s disease seek help only after 8 to 10 years of age. The condition has been divided into two forms - (1) Juvenile, (2) Adult. The adult cases are in fact the juvenile cases that have been asymptomatic. Juvenile form has been detected even before one year of age. As far as progression is concerned earlier the lesion develops faster is the growth and poorer is the prognosis. Some peripheral lesion may become stationary.

Coats divided the condition in three groups:

1. No vascular changes, only massive retinal or sub retinal exudation, no haemorrhage.

2.Multiple vascular changes, retinal and sub retinal haemorrhage, massive retinal and sub retinal exudates

3.Prominent retinal vascular changes, in the form of arterio venous communication and late exudation. This stage was later considered as separate entity not related to Coat’s disease and named as angiomatosis retinae.

To these three groups a separate clinical feature of miliary aneurysm was added and the condition was also known as Leber’s miliary aneurysm. However the condition was proved to be a milder and early form of Coat’s disease.27

The exact cause of the disease is not known, most probably there is incompetence of retinal vessels.

Clinical features28,29

Clinical features depend upon stage of the disease at which the child is brought. 1. It may be quiescent

(a) Discovered on routine fundus examination

(b) The child is brought with unilateral squint, diminished vision.

In the above stages the eye is non-congested without any signs in the anterior segment.

2.Stage of white reflex—This is commonest stage when a child either is brought by parents or referred by pediatrician who is justified to think it as retinoblastoma.

3.Stage of complication

(a) Congested eye (b) Raised tension

(c) Complicated cataract (d) Retinal detachment

4. Stage of blindness due to above conditions and total retinal detachment. Signs in a well established case:

1.There may be a retro lental white reflex in the pupil on oblique illumination.

2.On retinoscopy the reflex is grey instead of usual pink.

3.Fundus examination—Initially the media are clear. The changes are in the (a) Vessels

(b) Retina

Retinal vessels

The changes are seen both in the artery as well as veins. The changes are - Bunches of beading, kinking, and loop formation.

The calibre of the vessels are irregular, the vessels are tortuous, may show aneurysm formation. There may be establishment of communication between the artery and the veins. Neovascularisation may also take place.

Changes in the retina

In type I of original classification of Coat’s, the changes are predominantly in the retina or sub retinal space with almost normal vessels that become involved later leading the eye to the category of type II.

The retinal changes consist of ophthalmoscopically visible areas of greenish white or yellowish white areas of exudates with shinning spots. The shinning spots are cholesterol crystals, which are also seen in sub-retinal space. The exudation in the sub retinal space may elevate the retina and form a mass. The retinal detachment is exudative in nature. If not treated the retinal detachment extends leading to total detachment and the retina may be pushed as far as the posterior pole of the lens or very near to it. By this time a white reflex is visible that must be differentiated from retinoblastoma. There may be some haemorrhages in the vitreous as the disease progresses, the eye goes into secondary glaucoma, uveitis, complicated cataract and blindness. It may become painful and require enucleation.

Investigation

Most important investigation in presence of clear media is fluorescein angiography. The findings are variable according to stage of the disease and type of the disease. Common fluorescein angiographic findings in established cases of Coat’s disease are:

1.Vascular changes in the form of tortuosity, beading, loop formation, neovascularisation, multiple-aneurysms which were not visible with ophthalmoscope but stand out prominently on FFA.

2.Retinal changes consist of leak, area of non perfusion and capillary drop out. One of the characteristic appearance of fluorescein angiography is light bulb appearance of dilated aneurysm.

The next important investigation especially in hazy media is CT of the eye, orbit and skull and ultrasonography of the globe.

CT not only delineates the position of the retina, it shows the sub-retinal mass, there is no intraocular calcification which is common in retinoblastoma. CT of the brain excludes possibility of intracranial angiomatosis which is common in von Hippel Lindau’s disease, a condition that may otherwise be confused with Coat’s disease.

Differential diagnosis

The conditions that come in differential diagnosis are long. It is headed by retinoblastoma which is not only sight threatening but the life of the child is also jeopardised. The main points in favour of Coat’s disease are - Unilaterality, more common in boys; late age of onset, slow progressive. It never invades choroid or sclera hence it never becomes extraocular, being benign, no metastasis is seen on x-ray and CT. Intraocular calcification is absent in Coat’s disease. The most important similarity between the two conditions is white reflex in pupillary area. Other conditions that should be excluded are:

•Persistent hyper plastic primary vitreous

•Congenital cataract

•Traumatic cataract

•Intra ocular toxocariasis

•Retinal angioma

•Familial exudative vitreo retinopathy

•Total retinal detachment