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

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Fig. 12.54 (A) Atypical CHRPE; (B) magnification shows characteristic depigmentation at one margin; (C) adenomatous polyposis

Systemic associations

1Familial adenomatous polyposis (FAP) is an AD condition characterized by adenomatous polyps throughout the rectum and colon which usually start to develop in adolescence (Fig. 12.54C). If untreated, virtually all patients with FAP develop carcinoma of the colorectal region by the age of 50 years. As a result of the dominant inheritance pattern, intensive survey of family members is imperative. Over 80% of patients with FAP have atypical CHRPE lesions, which are present at birth. A positive criterion for FAP is the presence of at least four lesions whatever their size, or at least two lesions of which one is large. Such fundus lesions in a family member should therefore arouse suspicion of FAP but the absence of CHRPE lesions does not exclude FAP.

2Gardner syndrome is characterized by FAP, osteomas of the skull, mandible and long bones, and cutaneous soft tissue tumours such as epidermoid cysts, lipomas and fibromas.

3Turcot syndrome is an AD or AR condition characterized by FAP and tumours of the CNS, particularly medulloblastoma and glioma.

Combined hamartoma of the retina and RPE

Combined hamartoma of the retina and RPE is a rare, usually unilateral congenital malformation that predominantly affects males. It usually occurs sporadically in normal individuals and occasionally in patients with NF2 and Gorlin–Goltz syndrome.

1Histology shows RPE, sensory retina, retinal blood vessels and vitreoretinal membranes to varying degrees.

2Presentation is in late childhood or early adulthood with strabismus, blurred vision or metamorphopsia.

3Signs

•Deep greyish pigmentation with superficial whitish gliosis resulting in retinal wrinkling and vascular tortuosity.

•The lesion is usually juxtapapillary (Fig. 12.55A), peripapillary (Fig. 12.55B) or at the posterior pole (Fig. 12.55C).

•Peripheral lesions are uncommon (Fig. 12.55D).

•Large lesions may cause ‘dragging’ of the disc or macula.

•Uncommon associated findings include hard exudate formation and occasionally choroidal neovascularization at the margins of the lesion.

•Occasional associations include disc pit, disc drusen and disc coloboma.

4FA shows early hyperfluorescence of the vascular abnormalities and blockage by pigment (Fig. 12.55E); late phase shows intense hyperfluorescence due to leakage (Fig. 12.55F).

5 Treatment is not indicated.

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Fig. 12.55 Combined hamartoma of the retina and retinal pigment epithelium. (A) Small juxtapapillary lesion; (B) large peripapillary lesion with peripheral hard exudates; (C) large posterior pole lesion with ‘dragging’ of the disc; (D) peripheral lesion; (E) FA early venous phase shows hyperfluorescence of vascular lesions and blockage by pigment; (F) late phase shows intense hyperfluorescence due to leakage

(Courtesy of B Damato – fig. A; S Milewski – fig. C; C Barry – figs E and F)

Congenital hamartoma of the RPE

Congenital hamartoma of the RPE is a rare entity, usually incidentally diagnosed in asymptomatic children and young adults.

1Signs

•Small, jet-black, nodular lesion, with well-defined margins, which usually appears to involve the full-thickness of the retina and to spill onto the inner retinal surface in a mushroom configuration.

•The lesion is typically located immediately adjacent to the foveola and is 1.5 mm or less in base diameter (Fig. 12.56).

•Visual acuity is usually normal, but may occasionally be impaired as a result of surrounding foveal traction or central foveal involvement.

2 Treatment is not indicated.

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Fig. 12.56 Congenital hamartoma of the retinal pigment epithelium

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Paraneoplastic syndromes

Paraneoplastic retinopathies are rare diseases that might be missed or misdiagnosed by the unwary observer. Many of the patients present with visual symptoms before the primary malignancy is diagnosed. It is therefore important for clinicians to be familiar with these syndromes to detect the underlying malignancy as early as possible.

Bilateral diffuse uveal melanocytic proliferation

Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a very rare paraneoplastic syndrome occurring usually in patients with systemic, often occult, malignancy. It is characterized by proliferation of benign melanocytes in the outer choroid.

1Signs

•Multiple naevus-like choroidal lesions (Fig. 12.57).

•Multiple red-grey subretinal patches which may have a reticular pattern.

•Exudative retinal detachment.

•Rapidly developing cataracts.

•Vitreous and anterior chamber cells.

•Anterior uveal cysts and tumours.

•Episcleral nodules.

2 US shows diffuse choroidal thickening and multiple tumours.

3ERG is often reduced.

4Treatment of BDUMP itself is not available. Detection of an occult primary malignancy might enable early treatment to enhance survival. Successful treatment of the underlying primary tumour may be followed by regression of the BDUMP but without improvement in vision.

Fig. 12.57 Naevus-like lesions in diffuse uveal melanocytic proliferation

(Courtesy of A Leys)

Cancer-associated retinopathy

Cancer-associated retinopathy (CAR) is most frequently associated with small cell bronchial carcinoma, followed by gynaecological and breast cancer.

1Symptoms

•Subacute bilateral visual loss over 6–18 months.

•Visual symptoms precede the diagnosis of malignancy in half the cases, usually by several months.

•Positive visual phenomenon of shimmering or flickering lights.

•Progressive reduction of visual acuity, colour impairment, glare, photosensitivity and central scotoma attributed to cone dysfunction.

•Night blindness, impaired dark adaptation, ring scotoma and peripheral field loss due to rod dysfunction.

2Signs

•Fundus often appears normal on presentation.

•Attenuated arterioles, optic disc pallor and mild RPE changes develop as the disease progresses.

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3Investigations

aERG is severely attenuated under photopic and scotopic conditions; dark adaptation is abnormal.

b Lumbar puncture may show elevated cerebrospinal fluid protein and lymphocytosis.

cSearch for an underlying malignancy.

4Prognosis for both vision and life is poor.

Melanoma-associated retinopathy

The presentation of melanoma-associated retinopathy (MAR) differs from CAR because the visual symptoms usually arise after, rather than prior to, the diagnosis of cutaneous melanoma. There may be concurrent vitiligo. The specific antigen responsible has not been identified, but autoantibodies from MAR sera react against bipolar cells in human retina. Clinical and electrophysiological data also implicate the bipolar cells as the disease target abnormality in MAR.

1Symptoms consist of shimmering or flickering lights and nyctalopia.

2Signs

•Gradual central visual loss.

•Fundus appears normal initially, but optic disc pallor, retinal vascular attenuation and vitreous cells can develop.

3ERG shows marked reduction of dark-adapted and light-adapted b-wave and preservation of a-wave (normal photoreceptor function). Both the amplitude and implicit time of the b-wave are abnormal. MAR is characterized by a ‘negative ERG’, similar to the pattern seen in congenital stationary night blindness.

4Prognosis for vision is good.

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Chapter 13 – Retinal Vascular Disease

RETINAL CIRCULATION 534 DIABETIC RETINOPATHY 534

Introduction 534

Pathogenesis 535

Classification 536

Signs 536

Treatment 543

Advanced diabetic eye disease  549

RETINAL VENOUS OCCLUSIVE DISEASE 551 Pathogenesis 551

Predisposing factors 551 Systemic assessment 552 Branch retinal vein occlusion 552

Impending central retinal vein occlusion 555 Non-ischaemic central retinal vein occlusion  555

Ischaemic central retinal vein occlusion 557 Papillophlebitis 558

Hemiretinal vein occlusion 559

Systemic treatment in retinal vein occlusion  559

RETINAL ARTERIAL OCCLUSIVE DISEASE 559 Aetiology 559

Systemic assessment 561 Amaurosis fugax 562

Branch retinal artery occlusion 562 Central retinal artery occlusion 563 Cilioretinal artery occlusion 564

Treatment of acute retinal artery occlusion 564 Systemic prophylaxis following retinal artery occlusion  565

Asymptomatic retinal embolus 566

OCULAR ISCHAEMIC SYNDROME 566 HYPERTENSIVE DISEASE 567

Retinopathy 567

Choroidopathy  568

SICKLE-CELL RETINOPATHY 569 Sickling haemoglobinopathies  569

Proliferative retinopathy 570 Non-proliferative retinopathy 572 Anterior segment features 572

RETINOPATHY OF PREMATURITY 573 Pathogenesis 573

Active disease 573 Cicatricial disease  576

RETINAL ARTERY MACROANEURYSM 576

PRIMARY RETINAL TELANGIECTASIA 580

Idiopathic macular telangiectasia

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 581

Coats disease 582

EALES DISEASE 583 RADIATION RETINOPATHY 586 PURTSCHER RETINOPATHY 586

BENIGN IDIOPATHIC HAEMORRHAGIC RETINOPATHY 586 VALSALVA RETINOPATHY 588

LIPAEMIA RETINALIS 588

RETINOPATHY IN BLOOD DISORDERS 589 Leukaemia 589

Anaemia 589

Hyperviscosity  590

CONGENITAL VASCULAR ANOMALIES 591 Retinal macrovessel 591

Arteriovenous communications  592

Retinal circulation

Arterial system

1The central retinal artery is an end artery that enters the optic nerve approximately 1 cm behind the globe and is composed of the following three anatomical layers:

aThe intima, the innermost, is composed of a single layer of endothelium resting on a collagenous zone.

b The internal elastic lamina separates the intima from the media.

cThe media consists mainly of smooth muscle.

dThe adventitia is the outermost and is composed of loose connective tissue.

2Retinal arterioles arise from the central retinal artery. They contain smooth muscle within their walls, but unlike arteries the internal elastic lamina is discontinuous.

Capillaries

Retinal capillaries supply the inner two-thirds of the retina, with the outer third being supplied by the choriocapillaris. The inner capillary network (plexus) is located in the ganglion cell layer, with an outer plexus in the inner nuclear layer. Capillary-free zones are present around arterioles (Fig. 13.1A) and at the fovea (foveal avascular zone – FAZ). Retinal capillaries are devoid of smooth muscle and elastic tissue and their walls consist of the following (Fig. 13.1B):

1Endothelial cells form a single layer on the basement membrane and are linked by tight junctions that form the inner blood–retinal barrier.

2The basement membrane lies beneath the endothelial cells with an outer basal lamina enclosing pericytes.

3Pericytes lie external to endothelial cells and have multiple pseudopodial processes that envelop the capillaries. The pericytes have contractile properties and are thought to participate in autoregulation of the microvascular circulation.

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Fig. 13.1 Normal retinal capillary bed. (A) Periarteriolar capillary-free zone – flat preparation of Indian ink-injected retina; (B) endothelial cells with elongated nuclei and pericytes with rounded nuclei – trypsin digest preparation

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

Venous system

Retinal venules and veins drain blood from the capillaries.

1 Small venules are larger than capillaries but have a similar structure.

2Larger venules contain smooth muscle and merge to form veins.

3Veins contain a small amount of smooth muscle and elastic tissue in their walls and are relatively distensible. They gradually expand in diameter as they pass posteriorly towards the central retinal vein.

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Diabetic retinopathy

Introduction

Prevalence

The reported prevalence of diabetic retinopathy (DR) varies substantially between studies, even amongst contemporary diabetic populations in the same country, but is probably up to 40%. It is more common in type 1 diabetes than in type 2 and sight-threatening disease is present in up to 10%. Proliferative diabetic retinopathy (PDR) affects 5–10% of the diabetic population; type 1 diabetics are at particular risk with an incidence of about 60% after 30 years.

Risk factors

1Duration of diabetes is the most important risk factor. In patients diagnosed with diabetes before the age of 30 years, the incidence of DR after 10 years is 50%, and after 30 years 90%. DR rarely develops within 5 years of the onset of diabetes or before puberty, but about 5% of type 2 diabetics have DR at presentation. It appears that duration is a stronger predictor for proliferative disease than for maculopathy.

2Poor control of diabetes. It has been shown that tight blood glucose control, particularly when instituted early, can prevent or delay the development or progression of DR. However, a sudden improvement in control may be associated with progression of retinopathy in the near term. Type 1 diabetic patients appear to obtain greater benefit from good control than those with type 2. Raised HbA1c is associated with an increased risk of proliferative disease.

3Pregnancy is sometimes associated with rapid progression of DR. Predicating factors include greater pre-pregnancy severity of retinopathy, poor pre-pregnancy control of diabetes, control exerted too rapidly during the early stages of pregnancy, and the development of pre-eclampsia and fluid imbalance. The risk of progression is related to the severity of DR in the first trimester. If substantial DR is present, frequency of review should reflect the individual risk, and can be up to monthly. Diabetic macular oedema usually resolves spontaneously after pregnancy and need not be treated if it develops in later pregnancy.

4Hypertension, which is very common in patients with type 2 diabetes, should be rigorously controlled (<140/80). Tight control appears to be particularly beneficial in type 2 diabetics with maculopathy. Cardiovascular disease and previous stroke are also predictive.

5Nephropathy, if severe, is associated with worsening of DR. Conversely, treatment of renal disease (e.g. renal transplantation) may be associated with improvement of retinopathy and a better response to photocoagulation.

6Other risk factors include hyperlipidaemia, smoking, cataract surgery, obesity and anaemia.

Pathogenesis

DR is predominantly a microangiopathy in which small blood vessels are particularly vulnerable to damage from hyperglycaemia. Direct hyperglycaemic effects on retinal cells are also likely to play a role.

1Mechanisms of cellular damage include intracellular sorbitol accumulation, oxidative stress due to free radical excess, accumulation of advanced glycation end products and excessive activation of several protein kinase C isoforms. Disruption of ion channel function is an important early feature.

2Capillaropathy is characterized by death of pericytes (Fig. 13.2A), thickening of capillary basement membrane, loss of vascular smooth muscle cells and proliferation of endothelial cells. Haematological/rheological changes such as abnormalities of erythrocytes and leucocytes, increased platelet stickiness, and increased plasma viscosity may also contribute. Capillary dysfunction manifests with leakage and occlusion.

3Neovascularization is caused by capillary non-perfusion (Fig. 13.2B) which leads to retinal hypoxia which may progress to neovascularization extending preretinally (PDR) and intraretinally; intraretinal microvascular abnormalities (IRMA) are shunts that run within the retina from arterioles to venules. New vessel growth is thought to be caused by an imbalance between the elaboration of angiogenic and anti-angiogenic factors, putatively in an attempt to re-vascularize hypoxic retina.

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Fig. 13.2 The capillary bed in diabetic retinopathy. (A) Capillary closure with adjacent dilated and elongated capillaries – flat preparation of Indian ink-injected retina;

(B) degenerate pericytes which are eosinophilic – trypsin digest preparation; (C) new capillaries (arrows) on the inner retinal surface growing fromvessels in relation to non-perfused areas – flat preparation of Indian ink-injected retina

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

Many angiogenic stimulators have been identified; vascular endothelial growth factor (VEGF), especially VEGF-A, appears to be of particular importance. Others include platelet-derived growth factor and hepatocyte growth factor. Similarly, several endogenous inhibitors of angiogenesis have also been reported such as endostatin, angiostatin and pigment epithelium-derived factor. It has been hypothesized that a key determinant of the activity of retinopathy is the net balance between VEGF and endostatin.

Classification

The classification used in the Early Treatment Diabetic Retinopathy Study (the modified Airlie House classification) is widely used internationally. An abbreviated version is set out in Table 13.1, in conjunction with management guidelines. The following descriptive categories are also in widespread use in clinical practice:

1Background diabetic retinopathy (BDR) is characterized by microaneurysms, dot and blot haemorrhages and exudates. Generally the earlier signs of DR, although persisting as more advanced lesions appear.

2Diabetic maculopathy strictly refers to the presence of any retinopathy at the macula, but commonly reserved for significant changes, particularly vision-threatening oedema and ischaemia.

3Preproliferative diabetic retinopathy (PPDR) manifests cotton wool spots, venous changes, intraretinal microvascular anomalies (IRMA) and often deep retinal haemorrhages. PPDR indicates progressive retinal ischaemia, with a heightened risk of progression to retinal neovascularization.

4PDR is characterized by neovascularization on or within one disc diameter of the disc (NVD) and/or new vessels elsewhere (NVE) in the fundus.

4Advanced diabetic eye disease is characterized by tractional retinal detachment, significant persistent vitreous haemorrhage and neovascular glaucoma.

Table 13.1 -- Abbreviated Early Treatment Diabetic Retinopathy Study classification of diabetic retinopathy

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