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

FIGURE 5-8. Standardized electroretinogram from normal patient. Top to bottom: selective rod response; maximal combined rod–cone response; oscillatory potentials; selective cone response; 30-Hz flicker (cone) response.

investigators from different laboratories to compare selective rod and cone responses, as well as the maximal, combined response of the rods and cones, oscillatory potentials, and 30-Hz flicker. Cone dystrophy patients demonstrate preferential cone dysfunction early in the course of the disease (Fig. 5-9), whereas typical RP patients show predominantly abnormal rod responses (Fig. 5-10). Progressive reductions in amplitude and prolongation of implicit time are features of rod–cone and cone–rod dystrophies. Later in the course of many types of RP, the ERG may become nonrecordable. Nonhereditary pigmentary retinopathies show no change in the ERG over time. Congenital stationary night blindness has been classified into a Schubert–Bornschien type (Fig. 5-11) and a Riggs type,121,124 based on the ERG and dark adaptation. Miyake et al.105 further subclassified the former into a complete and incomplete type.

The ERG can also be useful in helping to diagnose the carrier state of X-linked recessive RP. B-wave amplitude reductions in the maximal, combined response of the rods and cones are often diagnostic. A loss of oscillatory potentials may help diagnose the carrier state in X-linked CSNB. A pattern of hyperpigmentation resembling “cracked mud” is probably more useful than the ERG in diagnosing the carrier state of choroideremia.

FIGURE 5-11. Standardized electroretinogram from patient with autosomal recessive congenital stationary night blindness. Top to bottom: nonrecordable selective rod response; markedly subnormal combined rod–cone response with preferential loss of the b-wave; minimal oscillatory potentials; subnormal cone response; delayed 30-Hz flicker (cone) response.

ERG testing of infants may be performed with the aid of the parents positioning the child, using a standard protocol; this allows results to be comparable to later ERGs when the patient is older. The ERG response may change over the first 6 months of life; some infants having nonrecordable ERGs as infants later develop negative-wave ERGs typical of CSNB. Therefore, a definitive diagnosis should be withheld until confirmed with repeat testing. Children from approximately 1 year to 6 or 7 years of age may find it difficult or impossible to cooperate with ERG testing. In these cases, a filament electrode may be used. If the diagnosis is of sufficient urgency, ERG under general anesthesia, or with chloral hydrate sedation with continuous monitoring of vital signs, may be indicated. These latter methods may not be comparable to standard ERG but can give a general idea of whether retinopathy is present.

Electro-oculography (EOG) is most often reserved for patients suspected of having Best disease.

Molecular testing is currently available for RP patients through several tertiary care centers as a part of ongoing research programs. Such testing will undoubtedly become more widely available in the coming years. Molecular testing has several potential benefits to patients as well as to the research commu-

nity. Such testing is capable of reliably identifying affected individuals before overt symptoms are present. Also, it allows one to reassure some family members at risk for disease that they will not develop it and to identify molecularly affected children who will benefit from closer follow-up. Moreover, molecular diagnosis provides a mechanism for different research centers to compare and pool results from patients with identical mutations, making it possible to evaluate correlations between genotype and phenotype. As these correlations are established in the literature, molecular testing may also be useful prognostically.

Treatment

Although the photoreceptor cell death of retinitis pigmentosa cannot at present be arrested or reversed, some visionthreatening complications can be successfully managed. Cataracts can be extracted when they become visually significant.9 However, visual acuity loss in retinitis pigmentosa is more likely to result from macular disease than from cataracts.44 A trial of systemic carbonic anhydrase inhibitors for RP patients with cystoid macular edema is indicated, particularly when associated with diffuse retinal pigment epithelial leakage on fluorescein angiography.45 Grid photocoagulation has also been suggested for macular edema in retinitis pigmentosa.62 An ophthalmologist should not overlook the potential benefit of refraction and referral to a low-vision clinic to optimize the RP patient’s visual function. It has been noted that, once vision drops below 20/40, further decline is often rapid.96 Therefore, children with RP require close follow-up to document changes in vision and to allow educators to tailor the school environment accordingly. Many children have adequate vision to attend regular school for many years, but should be counseled about the need to consider their progressive loss of acuity and color vision when making career choices.

Several rare syndromes have RP as an associated finding, and some of these disorders are caused by metabolic derangements that can be reversed or retarded with drugs, dietary manipulation, or plasmapheresis. In addition, vitamin A deficiency and certain drug toxicities, such as desferoxamine (desferal), can mimic RP but have a much better prognosis if diagnosed early in their course. Desferoxamine should be stopped immediately if vision drops and/or the ERG becomes abnormal. All patients with newly diagnosed retinitis pigmentosa should have a history

rule out ADRP if they have an affected parent or other relative. The most common forms of ADRP in North American and European pedigrees appear to have a later onset and less severe clinical course than X-linked and recessive forms. Although some patients report the onset of nyctalopia in the first decade,43 Tanino and Ohba found the onset of symptoms such as nyctalopia at a median age of 10.7 years in autosomal recessive disease and 23.4 years in autosomal dominant disease.136 Berson et al. found that older patients with ADRP are more likely to retain recordable ERG amplitudes than age-matched patients with ARRP.14

Massof and Finkelstein97 recognized two distinct types of RP among AD and simplex patients, and Lyness et al.93 also concluded that rod photoreceptor involvement appeared to be either diffuse or regionalized. Massof and Finkelstein type 1 patients have diffuse loss of rod sensitivity with patchy cone loss, absent rod ERG, and night blindness from infancy or childhood, whereas type 2 patients have a regionalized loss of both rod and cone function with adult-onset night blindness and some recordable rod ERG until late in life. Fishman et al. used a combination of ophthalmoscopy, electroretinography, visual fields, and central vision to further subdivide the regional ADRP patients into three groups with decreasing severity of symptoms.43

Rhodopsin gene mutations account for about 25% to 30% of cases of ADRP in North America (Fig. 5-12).34,131 Rhodopsin is the predominant protein contained within the discs of the rod photoreceptor outer segments. It plays a pivotal role in initiating the cascade of phototransduction that ultimately leads to the perception of light. There are at least nine different loci where dominant mutations cause RP. At this writing, the following genes have been identified: rhodopsin (RHO), retinal degeneration slow (RDS), leucine zipper motif protein (NRL), an oxygen-regulated photoreceptor protein (RP1),12 and the retinal fascin gene (FSCN2) in Japanese patients.139 RDS mutations account for about 2% of cases36 whereas NRL are responsible for 5.6%.12 Mutations in the gene for peripherin/RDS cause ADRP40,74 as well as the more benign pattern macular dystrophy. The human peripherin gene has sequence homology with the murine RDS (retinal degeneration slow) gene. Peripherin is a protein present in the peripheral aspect of the rod and cone photoreceptor discs. It may play a role in disc assembly or in maintaining the stability of the disc shape.31