Ординатура / Офтальмология / Английские материалы / Handbook of Pediatric Retinal Disease_Wright, Spiegel, Thompson_2006

Most lattice lesions are asymptomatic and are never associated with retinal detachments. Similarly, only about 1 in 365 patients with atrophic holes in lattice actually develops retinal detachments. Thus, prophylactic treatment of lattice lesions is not recommended. Tractional tears associated with lattice degeneration are an indication for demarcation with laser photocoagulation or cryotherapy because 10% to 27% of these will progress to retinal detachment. New holes and tears may develop in lattice with time. All patients with lattice degeneration should have a yearly indented peripheral retina exam. They should also be told about the symptoms of a retinal detachment and should return immediately for examination if any new floaters or photopsias occur.

STICKLER SYNDROME

In 1965, Stickler and associates described a syndrome they termed hereditary progressive arthro-ophthalmopathy.42 Stickler documented the association of high myopia, total retinal detachments in the first decade of life, and premature degenerative changes of the articular cartilage. Subsequent reports have demonstrated that Stickler syndrome is inherited as an autosomal dominant trait, and it is thought to be the most common autosomal dominant connective tissue dysplasia in the American Midwest.21

Ocular features include high myopia ( 8.00 D to 18.00 D) and frequent retinal detachments, often in the first decade of life. The vitreous appears optically clear with syneretic vitreous strands, vitreous membranes, and veils (Fig. 6-3). Vitreous degeneration can present as early as several months of age, or the vitreous can appear normal into the second decade of life. The retina often has perivascular pigmentary changes, but bone spicule-like pigment is not seen (Fig. 6-4). Chorioretinal degeneration and retinal breaks are prevalent, and these lead to complicated retinal detachments in up to 50% of affected eyes. Primary open-angle glaucoma or ocular hypertension occur in up to one-third of affected patients. Presenile nuclear sclerotic cataracts are often seen before age 45 and up to 20% of patients have peripheral cortical comma-shaped cataracts (Fig. 6-5) that may remain stationary throughout life.40,46

Systemic manifestations include orthopedic and orofacial abnormalities. Premature degenerative changes of the weight-

FIGURE 6-5. Peripheral cortical “wedge” cataract common in patients with Stickler syndrome.

radius, and the distal tibia (Figs. 6-6, 6-7). Orofacial anomalies such as submucous clefting of the palate, bifid uvula, and other abnormalities of the palate are noted in up to 75% of patients. Clinically, many patients appear to have midfacial flattening, but facial bone development is normal.46 Other associations include sensorineural hearing loss and the Pierre–Robin anomaly. Mitral valve prolapse is also found in up to 46% of patients with Stickler syndrome.40

The genetic defect in many Stickler pedigrees has been shown to be individual mutations in the procollagen II gene.1,6,27 Most of these mutations result in the premature termination of translation of the procollagen chain. Genetic heterogeneity exists because several other Stickler families have been excluded by linkage analysis at the collagen II locus.17,26 Collagen type II is the primary fibrillar collagen of secondary vitreous and cartilage, and it is not surprising that abnormalities in the structure or function of collagen II are involved in the pathogenesis of Stickler syndrome.

Management of Stickler syndrome includes early evaluation of those at risk, long-term monitoring of those affected, timely intervention, and genetic counseling.38 Children suspected to be affected with Stickler syndrome should have routine cycloplegic refractions, and myopic corrective lenses should be prescribed

when necessary to prevent ametropic amblyopia. Careful indented ophthalmoscopy looking for retinal breaks should be performed at least semiannually with treatment of new tears. Cataract extraction is often necessary when the nuclear sclerotic changes become visually significant. In cases of marked reduction of visual acuity, retinoscopy is often required to detect clear nuclear changes of the lens that can appear minimal by slit lamp examination. Retinal detachments are often difficult to manage because they can be associated with multiple posterior breaks, giant retinal tears, and cataracts. Otolaryngological consultation should be obtained to manage associated clefting and hearing abnormalities, and orthopedic evaluation should be sought to manage arthralgias and degenerative joint changes.

WAGNER’S DISEASE AND EROSIVE VITREORETINOPATHY

Wagner’s disease19,45 and erosive vitreoretinopathy5 are two extremely rare vitreoretinal disorders that should not be confused with the common Stickler syndrome. These disorders are both linked to a similar region on chomosome 5q13–14 known to encode two proteins (link protein and versican)4 that are involved in hyaluronan binding in the vitreous.34 The disorders are probably allelic at the same gene, with different mutations accounting for the marked disparity in retinal detachment rates between the disorders. It is possible that these two rare disorders are only present in relatives of the two separate families.

Unlike Stickler syndrome, neither Wagner’s disease nor erosive vitreoretinopathy has any of the systemic manifestations seen in Stickler syndrome. Both disorders have marked vitreous syneresis (described as optically clear), mild to moderate myopia ( 3.00 to 5.00), and early cataract formation. Both disorders are characterized by a characteristic progressive retinal pigment epithelium (RPE) and choroidal atrophy (described as erosion of the RPE) that progresses to bone spicule-like pigment formation, marked constriction of visual fields, and eventual loss of central visual fields with a choroideremia-type appearance.

More than 50% of patients with erosive vitreoretinopathy have severe rhegmatogenous retinal detachments, often from giant retinal tears and multiple posterior breaks. These detachments are very difficult to repair and should be referred to very experienced vitreous surgeons. Fortunately, patients with

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Wagner disease rarely demonstrate rhegmatogenous detachments,28 although vitreous traction is described in 15% of patients.19

Patients have early complaints of reduced night vision, but central vision is generally normal until reduced by cataract formation at age 30 to 40. Lens changes consist of dotlike opacities on the posterior and anterior lens cortex. Vision is generally restored to normal by cataract surgery in patients, but progressive visual field loss occurs secondary to the choroidal and retinal atrophy. Patients with erosive vitreoretinopathy also lose significant vision from retinal detachments and secondary complications of retinal detachment repair.

Psychophysical tests reveal concentric constriction of the visual field in both disorders. Electroretinography reveals reduced b-wave amplitudes that may progress to an extinguished ERG.

Management of both disorders consists of genetic counseling and cataract extraction when the lens changes become visually significant. Patients with erosive vitreoretinopathy should be screened in infancy and annually for peripheral retinal pathology, with timely surgical intervention instituted for retinal breaks and detachments. No intervention is known to prevent the pigmentary degeneration of the retina in either condition.

GOLDMANN–FAVRE SYNDROME

Goldmann–Favre vitreotapetoretinal degeneration is an exceedingly rare condition consisting of progressive loss of vision due to retinoschisis, progressive cataract, and pigmentary chorioretinal degeneration with bone spicule-like formation. It is inherited in an autosomal recessive fashion. It is quite rare and shows no sex predilection.

Most patients present between the ages of 10 and 20 because of night blindness and poor vision.41 Slit lamp examination reveals extensive liquefaction of the vitreous with multiple strands of condensed vitreous. Fundus changes include pale optic discs, sheathing of arteries and veins, and peripheral bone spicule-like pigmentary changes (Fig. 6-8). Extensive peripheral retinoschisis begins between the the equator and the ora serrata and may progressively involve the central retina. Generally, the central macula has microcystic changes and a “beaten copper” appearance. Fluorescein angiography can differentiate these

FIGURE 6-8. Vitreous strands, attenuation of retinal vessels, and peripheral pigmentary changes in a patient with Goldmann–Favre syndrome. The electroretinogram was nonrecordable.

changes from cystoid macular edema because there is no late staining of the cystic spaces in Goldmann–Favre syndrome. The macular changes may be isolated from or be continuous with the peripheral area of schisis.38 Presenile posterior subcapsular cataracts develop in most cases.

Patients with Goldmann–Favre syndrome have nondetectable or strikingly abnormal electroretinographic responses.14 In young patients with electroretinography (ERG) responses that are still recordable, scotopic a-waves have reduced amplitudes. The photopic and scotopic amplitudes may be essentially identical. Dark adaptation is also abnormal very early in the disease, with elevated rod thresholds or, in some cases, a monophasic cone-mediated threshold. Visual field testing reveals dense ring scotomas similar to typical retinitis pigmentosa.

Central visual loss is generally related to the macular retinoschisis and occurs early in the disease. The visual acuity is often reduced to 20/200 in childhood. The retinoschisis is presumed to be a splitting of the nerve fiber layer, and holes in both the outer and inner layer may occur.

No systemic manifestations are associated with Goldmann– Favre syndrome. Laser treatment and immunosuppressive therapy have been reported to be beneficial in some patients.

pigmented scar.31 Clinically, the stellate maculopathy can mimic cystoid macular edema, but it can be differentiated by the lack of late leakage on fluorescein angiography.38 Although bilateral inferotemporal retinoschisis has been considered the classical presentation of this disorder, only 40% of patients have peripheral retinoschisis in addition to the macular findings. The retinoschisis is a splitting of the nerve fiber layer with ballooning of the inner layer into the vitreous. The inner layer is quite thin and often contains large holes whereas the outer layer may contain small holes.11 Unsupported retinal vessels in the inner layer may give rise to recurrent vitreous hemorrhage. Fibrous condensations of vitreous cortex (vitreous veils) often overlie the areas of peripheral retinoschisis, and vitreous bands form that extend to retinal vessels. Posterior vitreous detachment with vitreous collapse may occur and is often associated with regression of retinoschisis in the areas of vitreous detachment.30

X-linked juvenile retinoschisis has no known systemic manifestations. The macular changes often progress rapidly during the first 5 years of life but then progress very slowly until the sixth or seventh decade. The visual acuity is usually around 20/60 at age 20 and gradually diminishes to 20/200 by age 60.16 Only rarely is good visual acuity maintained after the age of 60. Progression can vary from eye to eye in an affected individual or among related affected family members. Visual loss is generally related to macular involvement, although retinal detachment or vitreous hemorrhage may cause sudden visual loss.

Electroretinography in patients with juvenile X-linked retinoschisis typically reveals near normal a-waves with a selective reduction of the b-wave.33 Oscillatory potentials can also be abnormal with decreased cone responses and almost obliterated rod responses. These ERG changes are not always present, and some patients with known mutations in the XLRS1 gene have been demonstrated to have normal electroretinography findings. Visual field testing reveals absolute scotomas in areas of peripheral retinoschisis.

Two lines of evidence suggest that an abnormality of the Mueller cells causes both the macular and peripheral retinal changes in juvenile X-linked retinoschisis. First, the b-wave of the ERG results from a Mueller cell response to changes in extracellular potassium levels. Second, periodic acid–Schiff staining of intraretinal filaments, presumably formed by defective

Mueller cells, has been demonstrated histopathologically.11

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Juvenile X-linked retinoschisis progresses slowly, and prophylactic treatment of schisis (even with holes in schisis cavities) is not recommended. Management includes treatment of secondary retinal detachments and vitreous hemorrhages when they occur. The goal of therapy in the treatment of combined retinal detachment and congenital retinoschisis is closure of the outer layer and full-thickness retinal breaks, which can generally be accomplished by a scleral buckling procedure.38 No specific attempt is made to close inner layer breaks. If vitreous hemorrhage occurs, laser photocoagulation can be used to close the proximal portion of the bleeding vessel. The presence of genetic markers close to the juvenile retinoschisis gene and known mutations in the gene itself makes carrier detection and prenatal screening possible in some families.24

FAMILIAL EXUDATIVE

VITREORETINOPATHY

Familial exudative vitreoretinopathy (FEVR) was first described by Criswick and Schepens in 1969.12 They described heterotopia of the macula with temporal traction, posterior vitreous detachments with organized vitreous membranes, peripheral neovascularization, retinal traction with retinal breaks, and retinal detachments. The changes resemble retinopathy of prematurity, but affected patients have no history of premature birth or antenatal oxygen administration. Familial exudative vitreoretinopathy is inherited in an X-linked, autosomal recessive or autosomal dominant fashion and exhibits great variability of expression. Some patients have blinding bilateral retinal detachments in the first few years of life, whereas others have only a small area of avascular retina in the temporal periphery with no symptoms or complications throughout life.

The most constant ocular finding is an abrupt termination of retinal vessels along a scalloped edge at the equator (Fig. 6- 10). The avascular area can be quite extensive or confined to only several clock hours. Often an elevated fibrovascular scar in the temporal periphery is present, very similar to the cicatricial stage of retinopathy of prematurity.18 Peripheral neovascularization is present adjacent to this area, and the capillary bed posterior to the avascular zone is often dilated and more prominent. Maturation and organization of the fibrovascular scar produce the striking signs of retinal traction (“dragged disc” and macula