Ординатура / Офтальмология / Английские материалы / Clinical Ophthalmology A Systematic Approach 7th Edition_Kanski, Bowling_2011

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Fig. 12.33 Presentation of retinoblastoma. (A) Unilateral leukocoria; (B) secondary glaucoma and buphthalmos; (C) red eye due to uveitis; (D) iris nodules and pseudohypopyon; (E) orbital inflammation; (F) orbital invasion

(Courtesy of N Rogers – figs A and B; U Raina – fig. C)

Signs

Indirect ophthalmoscopy with scleral indentation must be performed on both eyes after full mydriasis. This is because without indentation pre-equatorial tumours may be missed (Fig. 12.34A) and one eye may harbour multiple tumours. The clinical signs depend on tumour size and growth pattern.

•An intraretinal tumour is a homogeneous, dome-shaped white lesion which becomes irregular, often with white flecks of calcification (Fig. 12.34B).

•An endophytic tumour projects into the vitreous as a white mass (Fig. 12.34C) that may ‘seed’ into the vitreous (Fig. 12.34D).

•An exophytic tumour forms subretinal, multilobular white masses (Fig. 12.34E) and causes overlying retinal detachment (Fig. 12.34F).

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Fig. 12.34 Signs of retinoblastoma. (A) Small peripheral tumour; (B) intraretinal tumour; (C) endophytic tumour; (D) endophytic tumour with vitreous seeding; (E) exophytic tumour; (F) total retinal detachment

(Courtesy of B Dixon-Romanowska – figs C and D; L MacKeen – fig. E)

Investigations

1Red reflex testing with a direct ophthalmoscope has been recommended as a screening test in the community. Any asymmetry indicates full eye examination with pupil dilatation and immediate referral to an ophthalmologist.

2Examination under anaesthesia includes the following:

•General examination for congenital abnormalities of the face and hands.

•Tonometry.

•Measurement of the corneal diameter and, if glaucoma is present, the axial length of the eye.

•Anterior chamber examination with a hand-held slit-lamp.

•Ophthalmoscopy, documenting all findings with colour drawings or photography.

3US is used mainly to assess tumour size. It also detects calcification within the tumour (Fig. 12.35A) and is helpful in the diagnosis of simulating lesions such as Coats disease.

4CT also detects calcification (Fig. 12.35B) but entails a significant dose of radiation and is performed only rarely.

5MR cannot detect calcification but it is superior to CT for optic nerve evaluation and detection of extraocular extension or pinealoblastoma (Fig. 12.35C), especially with contrast and fat suppression. MR may also be useful to differentiate retinoblastoma from simulating conditions.

6Systemic assessment includes physical examination and MR scans of the orbit and skull, as a minimum in high-risk cases. If these indicate the presence of metastatic disease then bone scans, bone marrow aspiration and lumbar puncture are also performed.

7Genetic studies require fresh tumour tissue from the enucleated eye and a blood sample for DNA analysis. Blood samples from the patient's relatives and a sperm sample from the father may also be useful.

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Fig. 12.35 Imaging of retinoblastoma. (A) B-scan with low gain shows echoes fromcalcification; (B) axial CTshows bilateral tumours and calcification; (C) sagittal MRshows a pinealoblastoma with secondary hydrocephalus

(Courtesy of K Nischal – fig. B; AD Singh, from Clinical Ophthalmic Pathology, Saunders Elsevier, 2007 – fig. C)

Treatment of small tumours

Tumours no more than 3 mm diameter and 2 mm thickness may be treated as follows:

1Photocoagulation using low-energy 532 nm argon or 810 nm diode laser achieves focal consolidation after chemotherapy. At least three treatment sessions are needed.

2Cryotherapy using the triple freeze-thaw technique is useful for pre-equatorial tumours without either deep invasion or vitreous seeding.

3Chemotherapy without other treatment can be attempted for a macular tumour, to conserve as much vision as possible, but there is an increased risk of tumour recurrence.

Treatment of medium-size tumours

Tumours up to 12 mm wide and 6 mm thick may be treated as follows:

1Brachytherapy using iodine-125 or ruthenium-106 is indicated for an anterior tumour if there is no vitreous seeding.

2Primary chemotherapy with intravenous carboplatin etoposide and vincristine (CEV) is given in three to six cycles according to the grade of retinoblastoma. Single agent chemoreduction with carboplatin alone has recently been found to give similar results to multi-agent therapy. Systemic treatment can be supplemented with sub-Tenon carboplatin injections. This may be followed by local treatment with cryotherapy or TTT to consolidate tumour control.

3External beam radiotherapy is avoided, if possible, in patients with heritable retinoblastoma because of the risk of inducing a second malignancy. Hypoplasia of the bony orbit can occur, especially if radiotherapy is administered in the first 6 months of life.

Treatment of large tumours

1Chemotherapy to shrink the tumour (chemoreduction), facilitating subsequent local treatment, thereby avoiding enucleation or external beam radiotherapy. Chemotherapy will also have a beneficial effect if a smaller tumour is present in the fellow eye or if there is a pinealoblastoma.

2Enucleation is indicated if there is rubeosis, vitreous haemorrhage or optic nerve invasion. It is also performed if chemoreduction fails or a normal fellow eye makes aggressive chemotherapy inappropriate and is also useful for diffuse retinoblastoma because of a poor visual prognosis and high risk of recurrence with other therapeutic modalities. Enucleation should be performed with minimal manipulation and it is imperative to obtain a long piece of optic nerve (12–15 mm). The orbital implant should be as large as possible. Tenon capsule and conjunctiva should be closed separately.

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Treatment of extraocular extension

1Adjuvant chemotherapy consisting of a 6-month course of CEV is given after enucleation by some centres if there is retrolaminar or massive choroidal spread.

2External beam radiotherapy is indicated when there is tumour extension to the cut end of the optic nerve at enucleation, or extension through the sclera.

Follow-up

•After radiotherapy or chemotherapy, tumours regress to a ‘cottage-cheese’ calcified mass (Fig. 12.36B), a translucent ‘fish-flesh’ mass, a mixture of both, or a flat atrophic scar.

•New tumours can develop in patients with heritable retinoblastoma, especially those treated at a very young age.

•If retinoblastoma has been treated conservatively EUA is necessary every 2 to 8 weeks until the age of 3 years, after which time examination without anaesthesia is performed every 6 months until the age of about 5 years, then annually until the age of about 10 years.

•Orbital MR is indicated in high risk cases for about 18 months. If the child has any risk of developing a second malignant neoplasm, the parents should be educated to be alert to features of pain, tenderness and swelling and to seek medical attention if there is no improvement in a week.

Fig. 12.36 Brachytherapy for retinoblastoma. (A) Before treatment; (B) ‘cottage-cheese’ appearance after treatment

(Courtesy of N Bornfeld)

Differential diagnosis

1Persistent anterior fetal vasculature (persistent hyperplastic primary vitreous) is confined to the anterior segment and often involves the lens.

•Presentation is with leukocoria (Fig. 12.37A) due to a retrolental mass into which elongated ciliary processes are inserted (Fig. 12.37B and C).

•With time, the mass contracts and pulls the ciliary processes centrally so that they become visible through the pupil.

•Complications include cataract (Fig. 12.37D) formation due to a capsular dehiscence.

•Treatment involving vitreoretinal surgery may be successful in selected early cases in salvaging some vision.

2Persistent posterior fetal vasculature is confined to the posterior segment and the lens is usually clear.

•Presentation is with leukocoria, strabismus or nystagmus.

•A dense fold of condensed vitreous and retina extends from the optic disc to the ora serrata and is associated with retinal

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detachment (Fig. 12.38).

•Treatment is not possible.

3Coats disease is almost always unilateral, more common in boys and tends to present later than retinoblastoma (see Ch. 13).

4Retinopathy of prematurity, if advanced, may cause retinal detachment and leukocoria. Diagnosis is usually straightforward because of the history of prematurity and low birth weight (see Ch. 13).

5Toxocariasis. Chronic toxocara endophthalmitis may cause a cyclitic membrane and a white pupil. A granuloma at the posterior pole may resemble an endophytic retinoblastoma (see Ch. 14).

6Uveitis may mimic the diffuse infiltrating type of retinoblastoma seen in older children. Conversely, retinoblastoma may be mistaken for uveitis, endophthalmitis or orbital cellulitis.

7Vitreoretinal dysplasia is caused by faulty differentiation of the retina and vitreous that results in a detached dysplastic retina (Fig. 12.39A) forming a retrolental mass with leukocoria (Fig. 12.39B). Other features include microphthalmos, shallow anterior chamber and elongated ciliary processes. Dysplasia may occur in isolation or in association with systemic abnormalities, most notably Norrie disease, incontinentia pigmenti (Bloch–Sulzberger syndrome) and Walker–Warburg syndrome.

aNorrie disease is an XL recessive disorder in which affected males are blind at birth or early infancy. It is caused by mutations in the NDP gene on chromosome Xp11. Systemic features include cochlear deafness and mental retardation.

bIncontinentia pigmenti is an XL dominant condition that is lethal in utero for boys. Mutations have been found in the NEMO gene on chromosome Xq28. It is characterized by a vesiculobullous rash on the trunk and extremities (Fig. 12.40A) which with time is replaced by linear pigmentation (Fig. 12.40B). Other features include malformation of teeth, hair, nails, bones and CNS.

cWalker–Warburg syndrome is an AR condition characterized by absence of cortical gyri and cerebellar malformations that may be associated with hydrocephalus and encephalocele. Neonatal death is common and survivors suffer severe developmental delay. Apart from vitreoretinal dysplasia other ocular features include Peters anomaly, cataract, uveal coloboma, microphthalmos and optic nerve hypoplasia.

8Other tumours

aRetinoma (retinocytoma) is a benign variant of retinoblastoma. It is characterized by a smooth, dome-shaped lesion, which slowly involutes spontaneously to a calcified mass associated with RPE alteration and chorioretinal atrophy (Fig. 12.41). The final appearance is remarkably similar to that of a retinoblastoma following irradiation. Rarely, a retinoma can later transform into a rapidly growing retinoblastoma.

bRetinal astrocytoma, which may be multifocal and bilateral (see below).

Fig. 12.37 Persistent anterior fetal vasculature. (A) Leukocoria; (B) retrolental mass with inserted ciliary processes; (C) early involvement; (D) advanced case with cataract

(Courtesy of K Nischal)

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Fig. 12.38 Persistent posterior fetal vasculature

Fig. 12.39 Vitreoretinal dysplasia. (A) Pathological specimen; (B) clinical appearance

(Courtesy of J Harry and G Misson, from Clinical Ophthalmic Pathology, Butterworth-Heinemann 2001 – fig. A)

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Fig. 12.40 Incontinentia pigmenti. (A) Vesciculobullous rash; (B) linear cutaneous pigmentation in an older child

Fig. 12.41 Retinoma

(Courtesy of K Nischal)

Astrocytoma

Astrocytoma of the retina and optic nerve head is a rare hamartoma, which does not usually threaten vision and does not require treatment. Most are endophytic, protruding into the vitreous, but exophytic subretinal tumours can occur. Astrocytomas may occasionally be encountered as incidental solitary lesions in normal individuals but are most frequently seen in tuberous sclerosis (see below) and occasionally in association with NF1 and retinitis pigmentosa. About 50% of patients with tuberous sclerosis have fundus astrocytomas which may be multiple and bilateral.

Diagnosis

1 Histology shows fibrillary astrocytes with small oval nuclei and cytoplasmic processes (Fig. 12.42A). 2 Presentation. Most tumours are asymptomatic and detected on screening for tuberous sclerosis.

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3Signs

•Yellowish, semitransparent round plaque or nodule (Fig. 12.42B).

•Large elevated mulberry-like lesion (Fig. 12.42C) that shows autofluorescence (Fig. 12.42D).

•Mixed type which is semitransparent in the periphery and calcified centrally.

•Most tumours are static, and long-standing lesions may become calcified (Fig. 12.42E).

4FA shows a prominent superficial vascular network within the tumour in the arterial phase followed by late leakage and staining (Fig. 12.42F).

Fig. 12.42 Astrocytoma. (A) Histology shows proliferation of fibrous astrocytes with small oval nuclei and cytoplasmic processes; (B) small peripheral lesion; (C) juxtapapillary mulberry-like lesion; (D) red-free image shows autofluorescence; (E) two calcified lesions; (F) FA shows staining

(Courtesy of J Harry – fig. A; P Gili – figs C and D; J Donald M Gass, from Stereoscopic Atlas of Macular Diseases, Mosby 1997 – fig. F)

Tuberous sclerosis

Tuberous sclerosis (Bourneville disease) is an AD phacomatosis characterized by the development of hamartomas in multiple organ systems from all primary germ layers. The classic triad of (a) epilepsy, (b) mental retardation and (c) adenoma sebaceum is only present in a minority of patients, but is diagnostic. About 60% of cases are sporadic and 40% are AD.

1Cutaneous signs

•Adenoma sebaceum, consisting of fibroangiomatous red papules with a butterfly distribution around the nose and cheeks, is universal (Fig. 12.43A).

•Ash leaf spots are hypopigmented macules on the trunk (Fig. 12.43B), limbs and scalp. In infants with sparse skin pigmentation they are best detected using ultraviolet light, under which they fluoresce (Wood lamp).

•Confetti skin lesions.

•Shagreen patches consist of diffuse thickening over the lumbar region.

•Fibrous plaques on the forehead.

•Skin tags (molluscum fibrosa pendulum).

•Café-au-lait spots.

•Subungual hamartomas (Fig. 12.43D).

2Neurological features

•Intracranial paraventricular subependymal astrocytic nodules (Fig. 12.43D) and giant cell astrocytic hamartomas.

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•Mental retardation.

•Seizures.

3Visceral tumours

•Renal angiomyolipomas and cysts.

•Cardiac rhabdomyomas.

•Pulmonary lymphangiomatosis.

4Ocular features, apart from fundus astrocytomas, include patchy iris hypopigmentation and atypical iris colobomas.

Fig. 12.43 Tuberous sclerosis. (A) Adenoma sebaceum; (B) ash leaf spot; (C) subungual hamartoma; (D) axial CTshows a periventricular astrocytic nodule

(Courtesy of K Nischal – fig. A; MA Mir, from Atlas of Clinical Diagnosis, Mosby 2003 – fig. B)

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Vascular retinal tumours

Capillary haemangioma

Overview

Retinal capillary haemangioma is a rare sight-threatening tumour that may occasionally occur in isolation, although about 50% of patients with solitary lesions and virtually all patients with multiple lesions have von Hippel–Lindau disease (VHL – see below). The prevalence of retinal tumours in VHL is approximately 60%. Vascular endothelial growth factor (VEGF) is important in the development of retinal lesions.

Diagnosis

1Histology. The tumour is composed of capillary-like vascular channels between large foamy cells that may represent histiocytes, endothelial cells or astrocytes (Fig. 12.44A).

2Presentation. The median age at diagnosis in patients with VHL is earlier (median 18 years) than in those without VHL (median 31 years). Tumours may be detected by screening of those at risk or because of symptoms due to macular exudates or retinal detachment.

3Signs

•An early tumour is a small, well-defined oval red lesion within the capillary bed between an arteriole and venule (Fig. 12.44B).

•A well-established tumour is a round orange-red mass usually located in the superoor inferotemporal periphery with dilatation and tortuosity of the supplying artery and draining vein extending from the optic disc (Fig. 12.44C).

•In a juxtapapillary tumour the dilated vessels are absent or less evident (Fig. 12.44D).

•A sessile tumour is an ill-defined placoid juxtapapillary lesion (Fig. 12.44E).

4FA shows early hyperfluorescence (Fig. 12.45A) and late leakage (Fig. 12.45B). There is also rapid filling and exit of dye.

5Complications

•Exudate formation in the area surrounding the tumour and/or at the macula (Fig. 12.46).

•Bleeding and leakage resulting in macular oedema and exudative retinal detachment.

•Fibrotic bands, which can cause tractional or rhegmatogenous retinal detachment.

•Vitreous haemorrhage, secondary glaucoma and phthisis bulbi.

6 Differential diagnosis includes Coats disease, retinal macroaneurysm and vasoproliferative tumour.

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