Ординатура / Офтальмология / Английские материалы / Comprehensive Ophthalmology_Khurana_2007

Fig. 11.32. Tractional retinal detachment in a patient with advanced diabetic retinopathy.

Classification

A. Primary tumours

1.Neuroblastic tumours. These arise from sensory retina (retinoblastoma and astrocytoma) and pigment epithelium (benign epithelioma and melanotic malignant tumours).

2.Mesodermal angiomata e.g., cavernous haemangioma.

3.Phakomatoses. These include: angiomatosis retinae (von Hippel-Lindau disease), tuberous sclerosis (Bourneville’s disease), neurofibromatosis (von Recklinghausen’s disease and encephalo-trigeminal angiomatosis (Sturge-Weber syndrome).

B. Secondary tumours

1.Direct extension e.g., from malignant melanoma of the choroid.

2.Metastatic carcinomas from the gastrointestinal tract, genitourinary tract, lungs, and pancreas.

3.Metastatic sarcomas.

4.Metastatic malignant melanoma from the skin.

RETINOBLASTOMA

It is a common congenital malignant tumour arising from the neurosensory retina in one or both eyes.

Incidence

1.It is the most common intraocular tumour of childhood occurring 1 in 20,000 live births.

2.Age. Though congenital, it is not recognised at birth, and is usually seen between 1 and 2 years of age.

3.Sex. There is no sex predisposition.

4.Race. It is rarer in Negroes than Whites.

5.Bilaterality. In 25-30 percent cases, there is bilateral involvement, although one eye is affected more extensively and earlier than the other.

Genetics and heredity

Retinoblastoma (RB) gene has been identified as 14 band on the long-arm of chromosome 13 (13q 14) and is a ‘cancer suppressor’ or ‘antioncogenic’ gene. Deletion or inactivation of this protective gene by two mutations (Knudson’s two hit hypothesis) results in occurrence of retinoblastoma.

Retinoblastoma may arise as hereditary and nonherditary forms.

1. Hereditary or familial cases. In such cases first hit (mutation) occurs in one of the parental germ cells before fertilization. This means mutation will occur in all somatic cells (predisposing to develop even nonocular tumour). Second hit (mutation) occurs late in postzygote phase and affects the second allele, resulting in development of retinoblastoma. Some facts about hereditary retinoblastoma are:

Accounts for 40% of all cases.

All bilateral cases and about 15% of the unilateral cases are hereditary.

Most hereditary cases are multifocal.

Some hereditary cases have trilateral retinoblastoma (i.e., have associated pinealoblastoma).

Inheritance is autosomal dominant and the risk of transmitting the gene mutation is 50%. Because of high peneterance 40% of offspring of a surviver of heraditary retinoblastoma will develop the tumour.

There are 40% chances of developing tumour in

a sibling of a child with bilateral retinoblastoma (with unaffected parents).

2. Non-hereditary or sporadic cases. In nonhereditary cases both hits (mutations) occur in the embryo after fertilization and in the same retinal cell. Some facts about non-hereditary (somatic) retinoblastoma are:

Accounts for 60% of all cases.

All non-hereditary cases are unilateral and unifocal and accounts for 85% of the all unilateral cases of retinoblastoma.

Patient is not predisposed to get second nonocular cancer.

Tumour is not transmissible.

Pathology

Origin. It arises as malignant proliferation of the immature retinal neural cells called, retinoblasts, which have lost both antioncogenic genes.

Histopathology. Growth chiefly consists of small round cells with large nuclei, resembling the cells of the nuclear layer of retina. These cells may present as a highly undifferentiated or well-differentiated tumour. Microscopic features of a well differentiated tumour include Flexner-Wintersteiner rosettes, (highly specific of retinoblastoma), Homer-Wright rosettes, pseudorosettes and fleurettes formation (Fig. 11.33). Other histologic features are presence of areas of necrosis and calcification.

Clinical picture

It may be divided into four stages:

I. Quiescent stage. It lasts for about 6 months to one year. During this stage, child may have any of the following features:

1.Leukocoria or yellowish-white pupillary reflex (also called as amaurotic cat’s eye appearance) is the commonest feature noticed in this stage (Fig. 11.34).

2.Squint, usually convergent, may develop in some cases.

3.Nystagmus is a rare feature, noticed in bilateral cases.

4.Defective vision. Very rarely, when the tumour arises late (3-5 years of age), the child may complain of defective vision.

5.Ophthalmoscopic features of tumour. In the early stages, before the appearance of leukocoria, fundus examination after full mydriasis may reveal the growth. Ophthalmoscopic signs in two types of retinoblastoma are as follows:

i.Endophytic retinoblastoma (Fig. 11.35A): It grows inwards from the retina into the vitreous cavity. On ophthalmoscopic examination, the tumour looks like a well circumscribed polypoidal mass of white or pearly pink in colour. Fine blood vessels and sometimes a haemorrhage may be present on its surface. In the presence of calcification, it gives the typical ‘cottage cheese’ appearance. There may be multiple growths projecting into the vitreous.

ii.Exophytic retinoblastoma (Fig. 11.35B). It grows outwards and separates the retina from the choroid. On fundus examination it gives appearance of exudative retinal

detachment (see page 278).

II. Glaucomatous stage. It develops when retinoblastoma is left untreated during the quiescent stage. This stage is characterised by severe pain, redness, and watering.

Signs. Eyeball is enlarged with apparent proptosis, conjunctiva is congested, cornea become hazy, intraocular pressure is raised. Occasionally, picture simulating severe, acute uveitis usually associated with pseudohypopyon and/or hyphaema may be the presenting mode (retinoblastoma masquerading as iridocyclitis).

Fig. 11.33. Histopathological picture of retinoblastoma.

Fig. 11.34. Leukocoria right eye in a patient with retinoblastoma.

Fig. 11.35. Drawing of the cross-section of the eyeball showing: A, endophytic retinoblastoma; B, exophytic retinoblastoma.

III. Stage of extraocular extension. Due to progressive enlargement, of tumour the globe bursts through the sclera, usually near the limbus or near the optic disc. It is followed by rapid fungation and involvement of extraocular tissues resulting in marked proptosis (Fig. 11.36).

IV. Stage of distant metastasis. It is characterised by the involvement of distant structures as follows:

1.Lymphatic spread first occurs in the preauricular and neighbouring lymph nodes.

2.Direct extension by continuity to the optic nerve and brain is common.

3.Metastasis by blood stream involves cranial and other bones. Metastasis in other organs, usually the liver, is relatively rare.

Differential diagnosis

Fig. 11.36. Fungating retinoblastoma involving the orbit.

as leukocoria are collectively called as ‘pseudoglioma'. A few common conditions are congenital cataract, inflammatory deposits in vitreous following a plastic cyclitis or choroiditis, coloboma of the choroid, the retrolental fibroplasia (retinopathy of prematurity), persistent hyperplastic primary vitreous, toxocara endophthalmitis and exudative retinopathy of Coats.

2.Endophytic retinoblastoma discovered on fundus examination should be differentiated from retinal tumours in tuberous sclerosis and neurofibromatosis, astrocytoma and a patch of exudative choroiditis.

3.Exophytic retinoblastoma should be differentiated from other causes of exudative retinal detachment (see page 278).

Diagnosis

1.Examination under anaesthesia: It should be performed in all clinically suspected cases. It should include fundus examination of both eyes after full mydriasis with atropine (direct as well as indirect ophthalmoscopy), measurement of intraocular pressure and corneal diameter.

2.Plain X-rays of orbit may show calcification which occurs in 75 percent cases of retinoblastoma.

1. Differential diagnosis of leukocoria. Various conditions other than retinoblastoma, which present

3.Lactic dehydrogenase (LDH) level is raised in aqueous humour.

4.Ultrasonography and CT scanning are very useful in the diagnosis. CT also demonstrates extension to optic nerve, orbit and CNS, if any (Fig. 11.37).

Treatment

1. Tumour destructive therapy. When tumour is diagnosed at an early stage I i.e., when tumour is involving less than half of retina and optic nerve is not involved (usually in the second eye of bilateral cases), it may be treated conservatively by any one or more of the following tumour destructive methods depending upon the size and location of the tumour:

Present recomendations are for sequential aggressive local therapy (SALT) comprising of multimodality therapy as below:

Chemoreduction followed by local therapy

(Cryotherapy, thermochemotherapy or brachytherapy) is recommended for large tumours (>12

mmin diameter)

Radiotherapy (external beam radiotherapy i.e., EBRT or brachytherapy) combined with chemotherapy is recommended for medium size tumour <12 mm in diameter and <8mm in thickness).

Cryotherapy is indicated for a small tumour (<4.5

mmindiameter and <2.5 mm in thickness) located anterior to equator.

Laser photocoagulation is used for a small tumour located posterior to equator <3 mm from fovea.

Thermotherapy with diode laser is used for a small tumour located posterior to equator away from macula.

Fig. 11.37. CT Scan showing retinoblastoma.

However, if the above modalities are not available, the eyeball should be enucleated without hesitation. 2. Enucleation. It is the treatment of choice when:

Tumour involves more than half of the retina.

Optic nerve is involved.

Glaucoma is present and anterior chamber is

involved.

The eyeball should be enucleated along with maximum length of the optic nerve taking special care not to perforate the eyeball.

If optic nerve shows invasion, postoperative treatment should include:

Radiotherapy (5000 rads) should be applied to the orbital apex.

Chemotherapy, consisting of vincristine, carboplatin, and etoposide which may be combined with cyclosporin should be supplemented.

3. Palliative therapy is given in following cases where prognosis for life is dismal in spite of aggressive treatment:

Retinoblastoma with orbital extension,

Retinoblastoma with intracranial extension, and

Retinoblastoma with distant metastasis. Palliative therapy should include combination of :

Chemotherapy,

Surgical debulking of the orbit or orbital exentration, and

External beam radiotherapy (EBRT)

Note: Exentration of the orbit (a mutilating surgery commonly performed in the past) is now not preferred by many surgeons.

Prognosis

1.If untreated the prognosis is almost always bad and the patient invariably dies. Rarely spontaneous regression with resultant cure and shrinkage of the eyeball may occur due to necrosis followed by calcification; suggesting role of some immunological phenomenon.

2.Prognosis is fair (survival rate 70-85%) if the eyeball is enucleated before the occurrence of extraocular extension.

3.Poor prognostic factors are: Optic nerve involvement, undifferentiated tumour cells and massive choroidal invasion.

ENUCLEATION

It is excision of the eyeball. It can be performed under local anaesthesia in adults and under general anaesthesia in children.

Indications

1.Absolute indications are retinoblastoma and malignant melanoma.

2.Relative indications are painful blind eye, mutilating ocular injuries, anterior staphyloma

and phthisis bulbi.

Surgical techniques (Fig. 11.38).

1.Separation of conjunctiva and Tenon’s capsule

(Fig. 11.38A): Conjunctiva is incised all around the limbus with the help of spring scissors. Undermining of the conjunctiva and Tenon’s capsule is done combinedly, all around up to the equator, using blunt-tipped curved scissors. This manoeuvre exposes the extraocular muscles.

2.Separation of extraocular muscles (Fig. 11.38B): The rectus muscles are pulled out one by one with the help of a muscle hook and a 3-0 silk suture is passed near the insertion of each muscle. The muscle is then cut with the help of

tenotomy scissors leaving behind a small stump carrying the suture. The inferior and superior oblique muscles are hooked out and cut near the globe.

3.Cutting of optic nerve (Fig. 11.38C): The eyeball is prolapsed out by stretching and pushing down the eye speculum. The eyeball is pulled out with the help of sutures passed through the muscle stumps. The enucleation scissiors is then introduced along the medial wall up to the posterior aspect of the eyeball. Optic nerve is felt and then cut with the scissors while maintaining a constant pull on the eyeball.

4.Removal of eyeball: The eyeball is pulled out of the orbit by incising the remaining tissue adherent to it.

5. Haemostasis is achieved by packing the orbital cavity with a wet pack and pressing it back.

6. Inserting an orbital implant (Fig. 11.38D): Preferably an orbital implant (made up of PMMA Medpor or hydroxyapatite) of appropriate size should be inserted into the orbit and sutured with the rectus muscles.

7.Closure of conjunctiva and Tenon’s capsule is done separately. Tenon’s capsule is sutured horizontally with 6-0 vicryl or chromic catgut. Conjunctiva is sutured vertically so that conjunctival fornies are retained deep with 6-0 silk sutures (Fig. 11.38 E) which are removed after 8-10 days.

8.Dressing. Antibiotic ointment is applied, lids are closed and dressing is done with firm pressure using sterile eye pads and a bandage.

Fitting of artifial prosthetic eye

Conforme may be used postoperatively so that the conjuctival fornices are retained deep. A proper sized prosthetic eye can be inserted for good cosmetic appearance (Fig. 11.39) after 6 weeks when healing of the enucleated socket is complete.

PHAKOMATOSES

Phacomatoses or neurocutaneous syndromes refer to a group of familial conditions (having autosomal dominant transmission) which are characterised by development of neoplasms in the eye, skin and central nervous system. Phakomatoses includes the following conditions:

1. Angiomatosis retinae (Von Hippel Lindau’s syndrome). This is a rare condition affecting males more often than females, in the third and fourth decade of life. The angiomatosis involves retina, brain, spinal cord, kidneys and adrenals. The usual clinical course of angiomatosis retinae comprises vascular dilatation, tortuosity and formation of aneurysms which vary

from small and miliary to balloon-like angiomas, followed by appearance of haemorrhages and exudates, resembling eventually the exudative retinopathy of Coats. Massive exudation is frequently complicated by retinal detachment which may be prevented by an early destruction of angiomas with cryopexy or photocoagulation.

2.Tuberous sclerosis (Bourneville disease). It is characterised by a classic diagnostic triad of adenoma sebaceum, mental retardation and epilepsy associated with hamartomas of the brain, retina and viscera. The name tuberous sclerosis is derived from the potatolike appearance of the tumours in the cerebrum and other organs. Two types of hamartomas found in the retina are: (1) relatively flat and soft appearing white or grey lesions usually seen in the posterior pole; and (2) large nodular tumours having predilection for the region of the optic disc.

3.Neurofibromatosis (von Recklinghausen’s disease). It is characterised by multiple tumours in the skin, nervous system and other organs. Cutaneous manifestations are very characteristic and vary from cafe-au-lait spots to neurofibromata. Ocular manifestations include neurofibromas of the lids and orbit, glioma of optic nerve and congenital glaucoma.

4.Encephalofacial angiomatosis (Sturge-Weber syndrome). It is characterised by angiomatosis in the form of port-wine stain (naevus flammeus), involving one side of the face which may be associated with choroidal haemangioma, leptomeningeal angioma and congenital glaucoma on the affected side.

ANATOMY AND PHYSIOLOGY

Anatomy of visual pathway

Pathway of visual sensations versus somatic sensations

LESIONS OF THE VISUAL PATHWAY

PUPILLARY REFLEXES AND THEIR ABNORMALITIES

DISEASES OF THE OPTIC NERVE

Congenital anomalies

Optic neuritis

Anterior ischaemic optic neuropathy

Papilloedema

Optic atrophy

Tumours

SYMPTOMATIC DISTURBANCES OF VISION

Night blindness

Day blindness

Colour blindness

Amaurosis

Amblyopia

Cortical blindness

Malingering

Hysterical blindness

Disorders of higher visual functions

OCULAR MANIFESTATIONS OF DISEASES OF CENTRAL NERVOUS SYSTEM

Infections

Aneurysms

Intracranial haemorrhages

ICSOLs

Demyelinating diseases

Head injury

ANATOMY AND PHYSIOLOGY

ANATOMY OF THE VISUAL PATHWAY

The visual pathway starting from retina consists of optic nerves, optic chiasma, optic tracts, lateral geniculate bodies, optic radiations and the visual cortex (Fig. 12.1).

Optic nerve

Each optic nerve (second cranial nerve) starts from the optic disc and extends up to optic chiasma, where the two nerves meet. It is the backward continuation of the nerve fibre layer of the retina, which consists of the axons originating from the ganglion cells. It also contains the afferent fibres of the pupillary light reflex.

Morphologically and embryologically, the optic nerve is comparable to a sensory tract. Unlike

peripheral nerves it is not covered by neurilemma (so it does not regenerate when cut). The fibres of optic nerve, numbering about a million, are very fine (2-10 µm in diameter as compared to 20 µm of sensory nerves).

Parts of optic nerve. The optic nerve is about 47-50 mm in length, and can be divided into 4 parts: intraocular (1 mm), intraorbital (30 mm), intracanalicular (6-9 mm) and intracranial (10 mm).

1.Intraocular part passes through sclera (converting it into a sieve-like structure—the lamina cribrosa), choroid and finally appears inside the eye as optic disc (see page 249).

2.Intraorbital part extends from back of the eyeball to the optic foramina. This part is slightly sinuous to give play for the eye movements. Posteriorly, near the optic foramina, it is closely surrounded by the annulus of Zinn and the origin of the four rectus muscles. Some fibres of

Fig. 12.1. Components of the visual pathway.

superior rectus muscle are adherent to its sheath here, and accounts for the painful ocular movements seen in retrobulbar neuritis. Anteriorly, the nerve is separated from the ocular muscles by the orbital fat.

3.Intracanalicular part is closely related to the ophthalmic artery which lies inferolateral to it and crosses obliquely over it, as it enters the orbit, to lie on its medial side. Sphenoid and posterior ethmoidal sinuses lie medial to it and are separated by a thin bony lamina. This relation accounts for retrobulbar neuritis following infection of the sinuses.

4.Intracranial part of the optic nerve lies above the cavernous sinus and converges with its fellow (over the diaphragma sellae) to form the optic

chiasma.

Meningeal sheaths. Pia mater, arachnoid and dura covering the brain are continuous over the optic nerves. In the optic canal the dura is firmly adherent with the surrounding bone. The subarachnoid and subdural spaces around the optic nerve are also continuous with those of the brain.

Optic chiasma

It is a flattened structure measuring 12 mm (horizontally) and 8 mm (anterioposteriorly). It lies over the tuberculum and diaphragma sellae. Fibres originating from the nasal halves of the retina decussate at the chiasma.

Optic tracts

These are cylindrical bundles of nerve fibres running outwards and backwards from the posterolateral aspect of the optic chiasma. Each optic tract consists of fibres from the temporal half of the retina of the same eye and the nasal half of the opposite eye. Posteriorly each optic tract ends in the lateral geniculate body. The pupillary reflex fibres pass on to pretectal nucleus in the midbrain through the superior brachium. some fibres terminate in the superior colliculus.

Lateral geniculate bodies

These are oval structures situated at the posterior termination of the optic tracts. Each geniculate body consists of six layers of neurons (grey matter) alternating with white matter (formed by optic fibres). The fibres of second-order neurons coming via optic tracts relay in these neurons.

Optic radiations

These extend from the lateral geniculate bodies to the visual cortex and consist of the axons of thirdorder neurons of visual pathway.

Visual cortex

It is located on the medial aspect of the occipital lobe, above and below the calcarine fissure. It is subdivided into the visuosensory area (striate area 17) that receives the fibres of the radiations, and the surrounding visuopsychic area (peristriate area 18 and parastriate area 19).

Blood supply of the visual pathway

The visual pathway is mainly supplied by pial network of vessels except the orbital part of optic nerve which is also supplied by an axial system derived from the central artery of retina. The pial plexus around different parts of the visual pathway gets contribution from different arteries as shown in Fig. 12.2.

Blood supply of the optic nerve head (Fig. 12.3) needs special mention.

The surface layer of the optic disc is supplied by capillaries derived from the retinal arterioles.

The prelaminar region is mainly supplied by centripetal branches of the peripapillary choroid with some contribution from the vessels of lamina cribrosa.

The lamina cribrosa is supplied by branches from the posterior ciliary arteries and arterial circle of Zinn.

The retrolaminar part of the optic nerve is supplied by centrifugal branches from central retinal artery and centripetal branches from pial

Fig. 12.2. Blood supply of posterior visual pathway.

plexus formed by branches from the choroidal arteries, circle of Zinn, central retinal artery and ophthalmic artery.

PATHWAY OF VISUAL SENSATIONS VERSUS SOMATIC SENSATIONS

The pathway of somatic as well as visual sensations consists of three neurons (Fig. 12.4). The corresponding parts of the pathway of these sensations are shown in Table 12.1.

Table 12.1. Somatic vs. visual sensations