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

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Retinopathy of prematurity

Pathogenesis

Retinopathy of prematurity (ROP) is a proliferative retinopathy affecting premature infants of very low birth weight, who have often been exposed to high ambient oxygen concentrations. The retina is unique among tissues in that it has no blood vessels until the fourth month of gestation, at which time vascular complexes emanating from the hyaloid vessels at the optic disc grow towards the periphery. These vessels reach the nasal periphery after 8 months of gestation, but do not reach the temporal periphery until about 1 month after delivery (Fig. 13.58). The incompletely vascularized retina is particularly susceptible to oxygen damage in the premature infant. A model of ROP suggests that the avascular retina produces VEGF (vascular endothelial growth factor) which in utero is the stimulus for vessel migration in the developing retina. With premature birth the production of VEGF is down-regulated by the relative hyperoxia and vessel migration is halted. Subsequently the increased metabolic demand of the growing eye allows excessive VEGF production which leads to the neovascular complications of ROP.

Fig. 13.58 Timing of vascularization of the peripheral retina

Active disease

Location

For the purpose of defining the anteroposterior location of ROP, three concentric zones centred on the optic disc are described (Fig. 13.59). Zone 1 is bounded by an imaginary circle the radius of which is twice the distance from the disc to the centre of the macula. Zone 2 extends concentrically from the edge of zone 1; its radius extends from the centre of the disc to the nasal ora serrata. Zone 3 consists of a residual temporal crescent anterior to zone 2.

The approximate temporal extent of zone 1 can be determined by using a 25 or 28 D condensing lens. By placing the nasal edge of the optic disc at one edge of the field of view, the limit of zone 1 is at the temporal field of view.

Fig. 13.59 Grading of retinopathy of prematurity according to location

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Extent

Extent of involvement is determined by the number of clock hours of retina involved (30° sectors).

Staging

The following five stages are used to describe the abnormal vascular response at the junction of immature avascular peripheral retina and vascularized posterior retina. Because more than one ROP stage may be present in the same eye, staging for the eye as a whole is determined by the most severe manifestation.

Stage 1 (demarcation line) is a thin, flat, tortuous, grey-white line running roughly parallel with the ora serrata. It is more prominent in the temporal periphery. There is abnormal branching or ‘arcading’ of vessels leading up to the line (Fig. 13.60A).

Stage 2 (ridge) arises in the region of the demarcation line, has height and width, and extends above the plane of the retina. Blood vessels enter the ridge and small isolated neovascular tufts (‘popcorn’) may be seen posterior to it (Fig. 13.60B).

Stage 3 (extraretinal fibrovascular proliferation) extends from the ridge into the vitreous (Fig. 13.60C). It is continuous with the posterior aspect of the ridge, causing a ragged appearance as the proliferation becomes more extensive. The severity of stage 3 can be subdivided into mild, moderate and severe depending on the extent of extraretinal fibrous tissue infiltrating the vitreous. The highest incidence of this stage is around the post-conceptual age of 35 weeks.

Stage 4 (partial retinal detachment) is divided into extrafoveal (stage 4A – Fig. 13.60D) and foveal (Stage 4B). The detachment is generally concave and circumferentially orientated. In progressive cases the fibrous tissue continues to contract and the detachment increases in height and extends anteriorly and posteriorly.

Stage 5 is a total retinal detachment.

(Courtesy of L MacKeen – figs A, C and D; P Watts – figs B and F)

Other features

1‘Plus’ disease signifies a tendency to progression and is characterized by the following:

•Failure of the pupil to dilate associated with gross vascular engorgement of the iris.

•Vitreous haze.

•Dilatation of veins and tortuosity of the arteries involving at least two quadrants of the posterior fundus (Fig. 13.60E).

•Increasing preretinal and vitreous haemorrhage.

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When these changes are present, a plus sign is added to the stage number.

2‘Pre-plus’ disease is characterized by abnormal dilatation and tortuosity that is insufficient to be designated as plus disease.

3‘Threshold’ disease is defined as five contiguous or eight cumulative clock hours of extraretinal neovascularization (stage 3 disease) in zone 1 or zone 2, associated with plus disease, and is an indication for treatment.

4Aggressive posterior (‘rush’ disease) is uncommon but if untreated usually progresses to stage 5. It is characterized by its posterior location, prominence of plus disease and ill-defined nature of the retinopathy. It is most commonly observed in zone 1 and does not usually progress through the classical stages 1–3. Although the clinical features of ROP usually take several weeks to develop, rarely the disease can progress from stage 1 to rush disease within a few days.

5Other ocular morbidity. Very low birth weight infants, especially those treated for ROP, are at a substantially higher risk of developing strabismus and myopia than term infants and require follow-up till the age of visual maturity.

Regression

In about 80% of cases ROP regresses spontaneously by a process of involution, or by evolution from a vasoproliferative to fibrotic phase leaving few if any residua. Spontaneous regression may even occur in eyes with partial retinal detachments.

Screening

Babies born at or before 31 weeks gestational age, or weighing 1500 g or less, should be screened for ROP. This may involve indirect ophthalmoscopy with a 28 D lens or a 2.2 panfunduscopic Volk lens, or a wide field retinal camera. Screening should begin 4–7 weeks postnatally to detect the onset of threshold disease. Subsequent review should be at 1–2-weekly intervals, depending on the severity of the disease and continue until retinal vascularization reaches zone 3. The pupils in a premature infant are dilated with 0.5% cyclopentolate and 2.5% phenylephrine. Only about 8% of babies screened actually require treatment.

Treatment

1Laser photocoagulation of avascular immature retina is recommended in infants with threshold disease (Fig. 13.60F). This is successful in 85% of cases, but the remainder progress to retinal detachment in spite of treatment. Laser therapy has largely replaced cryotherapy because visual and anatomical outcomes are superior, and because laser induces less myopia.

2Intravitreal anti-VEGF agents. Bevacizumab has been introduced in many centres for the treatment of ROP, but optimal timing, frequency, and dose are yet to be established. The potential for systemic complications and long-term effects is also undefined in this age group.

3Lens-sparing pars plana vitrectomy for tractional retinal detachment not involving the macula (stage 4a) can be performed successfully with respect to anatomical and visual outcome. The visual outcome in stages 4b and 5, in which the macula is involved, is often disappointing despite successful reattachment.

Cicatricial disease

About 20% of infants with active ROP develop cicatricial complications, which range from innocuous to extremely severe. In general, the more advanced or the more posterior the proliferative disease at the time of involution, the worse the cicatricial sequelae.

Stage 1 shows peripheral retinal pigmentary disturbance and haze at the vitreous base (Fig. 13.61A).

Stage 2 manifests temporal vitreoretinal fibrosis and straightening of vascular arcades (Fig. 13.61B) followed by ‘dragging’ of the macula and disc (Fig. 13.61C). This may lead to a pseudoexotropia due to resultant exaggeration of angle kappa.

Stage 3 is characterized by more severe peripheral fibrosis with contracture and a falciform retinal fold (Fig. 13.61D). Stage 4 shows an incomplete ring of retrolental fibrovascular tissue with partial retinal detachment (Fig. 13.61E).

Stage 5 features a complete ring of retrolental fibrovascular tissue with total retinal detachment, a picture formerly known as ‘retrolental fibroplasia’ (Fig. 13.61F). Secondary angle-closure glaucoma may develop due to progressive shallowing of the anterior chamber caused by a forward movement of the iris-lens diaphragm and the development of anterior synechiae. Treatment involving lensectomy and anterior vitrectomy may be tried but the results are often poor.

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Fig. 13.61 Cicatricial retinopathy of prematurity. (A) Stage 1 – peripheral pigmentary disturbance; (B) early stage 2 – straightening of vascular arcades; (C) late stage 2 – ‘dragging’ of the disc and macula; (D) stage 3 – falciformfold; (E) stage 4 – retrolental fibrovascular tissue and partial retinal detachment; (F) stage 5 – total retinal detachment

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Retinal artery macroaneurysm

A retinal artery macroaneurysm is a localized dilatation of a retinal arteriole; it usually occurs in the first three orders of the arterial tree. It has a predilection for elderly hypertensive women and involves only one eye in 90% of cases.

Diagnosis

1Presentation

•Insidious impairment of central vision due to leakage involving the macula.

•Sudden visual loss resulting from haemorrhage is less common.

2Signs

•A saccular or fusiform arteriolar dilatation, most frequently occurring at a bifurcation or an arteriovenous crossing along the temporal vascular arcades.

•The aneurysm may enlarge to several times the diameter of the artery.

•Associated retinal haemorrhage is present in 50% of cases (Fig. 13.62A).

•Multiple macroaneurysms along the same or different arterioles may occasionally be present.

3FA findings are dependent on the patency of the lesion and any associated haemorrhage. The typical appearance is that of immediate uniform filling of the macroaneurysm (Fig. 13.62B) with late leakage (Fig. 13.62C). Incomplete filling is due to partial or complete obliteration of the lumen by thrombosis.

4Course

aChronic leakage resulting in retinal oedema with accumulation of exudates is common (Fig. 13.63A and B) and may result in permanent loss of central vision.

bRupture resulting in haemorrhages which may be intraretinal (Fig. 13.63C), subretinal or preretinal (Fig. 13.63D). In these cases the underlying lesion may be overlooked and the diagnosis missed.

cSpontaneous involution following thrombosis and fibrosis is very common (Fig. 13.63E) and may precede or follow the development of leakage or haemorrhage.

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Fig. 13.62 (A) Retinal artery macroaneurysmassociated with haemorrhage; (B) FA early venous phase shows hyperfluorescence of the microaneurysm, which is surrounded by hypofluorescence due to blockage by blood; (C) late phase shows increased hyperfluorescence due to leakage

(Courtesy of P Saine)

Fig. 13.63 Retinal artery macroaneurysm. (A) Surrounded by a fine ring of exudates; (B) dense ring of exudates; (C) two macroaneurysms, one of which is associated with extensive exudates and intraretinal haemorrhages; (D) preretinal haemorrhage; (E) spontaneous involution of three macroaneurysms

Prognosis

Eyes with vitreous or premacular haemorrhage tend to recover good vision, but central visual function in those with submacular haemorrhage generally remains poor.

Management

1Observation in anticipation of spontaneous involution is indicated in eyes with good visual acuity in which the macula is not threatened, and in those with mild retinal haemorrhage without significant oedema or exudation. In most cases following retinal or vitreous haemorrhage the macroaneurysm thromboses and laser coagulation is not required.

2Laser photocoagulation may be considered if oedema or exudates threaten or involve the fovea (Fig. 13.64A), particularly if there is documented visual deterioration. The burns may be applied to the lesion itself, the surrounding area, or both (Fig. 13.64B). It may take several months for the oedema and hard exudates to absorb.

3YAG laser hyaloidotomy may be considered in eyes with large non-absorbing preretinal haemorrhage overlying the macula (Fig. 13.64C) in order to disperse the blood into the vitreous cavity, from where it may be absorbed more quickly (Fig. 13.64D).

4Intravitreal injection of expandable gas with face-down positioning is often effective in shifting submacular haemorrhage away from the macula. Adjunctive intravitreal recombinant tissue plasminogen activator (rTPA) may be used.

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Fig. 13.64 Treatment of complications of retinal artery macroaneurysm. (A) Hard exudates at the macula due to chronic leakage; (B) following laser photocoagulation; (C) large preretinal haemorrhage overlying the macula; (D) following YAGlaser hyaloidotomy the blood is dispersing into the vitreous

(Courtesy of P Gili – figs C and D)

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Primary retinal telangiectasiA

Retinal capillary telangiectasia is relatively common. Most cases, however, are clearly secondary to another retinal condition, typically involving inflammation or vascular occlusion; examples include diabetic retinopathy and retinal venous occlusion. Primary retinal telangiectasis comprises a group of rare, idiopathic, congenital or acquired retinal vascular anomalies characterized by dilatation and tortuosity of retinal blood vessels, multiple aneurysms, vascular leakage and the deposition of hard exudates. Retinal telangiectasis involves the capillary bed, although the arterioles and venules may also be involved. The vascular malformations often progress and become symptomatic later in life.

Idiopathic macular telangiectasia

Idiopathic macular telangiectasia (IMT) is a rare condition of unknown pathogenesis. There are occasional reports of occurrence in close relatives, and although IMT is generally not considered familial it is suspected that a genetic element has a role. An updated and simplified classification has recently been suggested, reflecting increased knowledge of clinical and imaging features.

Type 1: aneurysmal telangiectasia

This may be closely related to Coats disease and may involve a variable area of the fundus including the periphery.

1Presentation is typically in an otherwise healthy middle-aged patient, usually male, with mild to moderate blurring of vision in one eye (occasionally both).

2Signs

•Telangiectasia, microaneurysms and later larger aneurysms.

•Macular oedema, including cystoid changes.

•Chronic leakage and lipid deposition (Fig. 13.65A).

3 OCT demonstrates retinal thickening, CMO, and localized exudative retinal detachment.

4FA shows telangiectasia and multiple capillary, venular and arteriolar aneurysms (Fig. 13.65B) and late leakage (Fig. 13.65C). There is minimal non-perfusion.

5Treatment by laser photocoagulation to areas of leakage may occasionally be beneficial in preventing visual loss from chronic CMO and exudation. Intravitreal VEGF inhibitors may reduce macular oedema and improve vision.

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Fig. 13.65 Idiopathic macular telangiectasia – type 1. (A) Telangiectasis surrounded by a ring of exudates; (B) FA early phase shows telangiectasia temporal to the fovea; (C) FA late phase shows leakage.

Type 2: perafoveal telangiectasia

1Presentation is in middle age with blurring commonly affecting both eyes. Males and females are equally affected. This form is more common than type 1, and has the worst visual prognosis. In contrast to type 1, findings are limited to the perifoveal area.

2Signs

•Initially there is greyish loss of juxtafoveolar retinal transparency, initially temporal to and later surrounding the fovea.

•Telangiectasia may not be visible clinically but can be demonstrated by red-free photography.

•Cystic foveal atrophy without leakage is associated with falling visual acuity.

•Fine crystalline deposits and small RPE plaques develop in some patients (Fig. 13.66A); aneurysms and lipid deposition do not generally occur.

•Later there is intraand subretinal neovascularization, increase in intraretinal oedema and occasionally choroidal neovascularization.

3OCT shows diffuse retinal thickening, even before telangiectasia is apparent, and foveal cystic degenerative change.

4FA in early disease shows bilateral perifoveal telangiectasia (Fig. 13.66B) with diffuse leakage (Fig. 13.66C) but without CMO. CNV and CMO may be demonstrated in later disease.

5Treatment with intravitreal anti-VEGF agents decrease leakage on FA in the non-proliferative stage but is probably not helpful visually. They may retard subretinal neovascularization in the proliferative stage, and may also be considered for subfoveal choroidal neovascularization.

Fig. 13.66 Idiopathic macular telangiectasia – type 2. (A) Macular crystals and small plaques of RPE; (B) FA early phase shows perifoveal telangiectasias; (C) FA late phase shows leakage

(Courtesy of J Donald M Gass, from Stereoscopic Atlas of Macular Diseases, Mosby 1997 – fig. A)

Occlusive telangiectasia

This is an extremely rare condition. The manifestations relate to capillary occlusion rather than telangiectasia, and probably result from a distinct pathogenesis. It has been omitted from the new classification system but was categorized as types 3A and B under the previous scheme. It carries a poor visual prognosis, and is frequently associated with systemic haematological or neurological disease.

1 Presentation is in the 6th decade with slowly progressive loss of central vision.

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2Signs

•Marked aneurysmal dilatation of terminal capillaries with progressive occlusion of parafoveal capillaries (Fig. 13.67A).

•Optic atrophy may be present in some cases.

3FA shows widening of the FAZ but absence of leakage (Fig. 13.67B).

Fig. 13.67 Occlusive telangiectasia. (A) Occlusion of parafoveal capillaries; (B) FA shows aneurysmal dilatation of terminal capillaries and widening of FAZ

(Courtesy of J Donald M Gass, from Stereoscopic Atlas of Macular Diseases, Mosby 1997)

Coats disease

Coats disease is an idiopathic retinal telangiectasia generally of onset in early childhood. It is associated with intraretinal and subretinal exudation, and frequently exudative retinal detachment, without signs of vitreoretinal traction. About 75% of patients are male and the great majority have involvement of only one eye. Although it is not clearly inherited, a genetic predisposition may be involved as at least some patients have a somatic mutation in the NDP gene, which is also mutated in Norrie disease. It is now considered that Leber miliary aneurysms, previously regarded as a distinct condition, represents a generally milder form of the same disease, presenting later, in a more localized pattern, and carrying a better visual prognosis.

Diagnosis

1Presentation is most frequently in the first decade of life (average 5 years) with unilateral visual loss, strabismus or leukocoria (Fig. 13.68A). Occasionally the condition may present in later childhood and rarely in adult life.

2Signs

•Telangiectasia most often in the inferior and temporal quadrants between the equator and ora serrata (Fig. 13.68B).

•Intraretinal (Fig. 13.68C) and subretinal exudate formation (Fig. 13.68D).

•Progression of intraretinal and subretinal yellowish exudation often affecting areas remote from the vascular abnormalities, particularly the macula (Fig. 13.68E).

•Exudative retinal detachment (Fig. 13.68F).

3 FA in mild cases shows early hyperfluorescence of the telangiectasia (Fig. 13.69A) and late staining and leakage (Fig. 13.69B). 4 OCT may be useful for the assessment of the macula in cooperative older children.

5Complications include rubeosis iridis, glaucoma, uveitis, cataract and phthisis bulbi.

6 Association. Atypical pigmentary retinopathy is seen in a small minority of patients (see Fig. 15.12).

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