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BCSC 12 - Ch. 12 Hereditary Retinal and Choroidal Dystrophies
Terms in this set (88)
ERG in different dz chart
Panretinal pigmentary disturbances of the RPE and retina are divided into 2 large groups:
(1) primary retinitis pigmentosa
(2) secondary pigmentary retinopathy
Describe Primary retinitis pigmentosa (RP) ?
refers to hereditary disorders that diffusely involve photoreceptor and pigment epithelial function;
these conditions are characterized by progressive visual field loss and abnormal ERG responses.
The disease process is confined to the eyes and is not associated with other systemic manifestations.
Describe Secondary pigmentary retinopathy?
refers to disorders in which the retinal degeneration is associated with single- or multiple-organ system disease.
Occasionally, the term pigmentary retinopathy is used purely descriptively, and no associated disease is present.
Typical fundus findings in RP include ?
arteriolar narrowing, variable waxy pallor of the disc, and variable amounts of bone spicule-like pigment changes (Fig 12-2).
The peripheral retina and RPE appear atrophic even if spicules are absent (RP sine pigmento), and the macula typically shows a loss of the foveal reflex and irregularity of the vitreoretinal interface.
Cystoid macular edema (CME) is occasionally present.
Vitreous cells and mild posterior subcapsular cataracts are also commonly observed.
retinitis punctata albescens fundus photo?
numerous deep retinal white dots
ERG response in RP typically shows ?
Loss or marked reduction in rod- more than cone-derived responses.
Both a- and b-waves are reduced because the photoreceptors are primarily involved. The b-waves are characteristically prolonged in time as well as diminished in amplitude.
Persons with the carrier state of X-linked recessive RP often show a mild reduction or delay in b-wave responses.
Late in the course of many types of RP, the ERG responses may become undetectable with conventional testing.
An undetectable ERG signal is not diagnostic of RP but simply documents severe loss of retinal function.
acquired causes of retinal degeneration that can mimic RP, include?
Previous ophthalmic artery occlusion, diffuse uveitis, infections such as syphilis, paraneoplastic syndromes, and retinal drug toxicity.
Secondary forms of pigmentary retinopathy associated with metabolic or other organ system disease must also be considered.
Picture of demarcated RP on fundus photo
Define Sectorial RP ?
refers to disease involving only 1 or 2 sectors of the fundus.
This condition is generally symmetric in both eyes, which helps rule out acquired damage (eg, from trauma, vascular insult, or inflammation).
Describe cone-rod dystrophy and difference from RP?
Where cone-derived ERG responses are more abnormal than the rod ERG responses
present with macular involvement or markedly reduced visual acuity very early in the course of disease, which is unusual for RP.
Visual field loss may progress outward from the center rather than inward (central RP).
Some patients show a tight ring scotoma within the central 20° or 30° (pericentral RP).
This group of regional variants is probably heterogeneous because most of the cases appear sporadic and few are well characterized clinically or genetically.
Describe Unilateral RP?
most cases of unexplained unilateral pigmentary retinopathy are probably postinflammatory or posttraumatic.
In authentic cases, the clinical presentation and findings in the involved eye are similar to those of typical RP.
Before making a diagnosis of unilateral RP, the clinician must first rule out secondary causes, document a normal ERG response in the unaffected eye, and monitor the patient for at least 5 years to rule out bilateral but highly asymmetric disease.
mild RP (a form of stationary night blindness) is associated with what mutation?
codon 90 mutations
Severe RP (a form of stationary night blindness) is associated with what mutation?
mutations that interfere with the attachment of vitamin A to the rhodopsin protein.
CME can be managed with use of ___?
oral carbonic anhydrase inhibitors, such as acetazolamide (Fig 12-5), or intravitreal injection of triamcinolone acetonide in refractory cases.
Treatment-resistant CME is common.
One large study reported that high daily doses of vitamin A palmitate (15,000 IU/day) can slow the decline in ERG response in RP by approximately 20% per year. However, the benefits must be weighed against the risk of long-term ____?
liver toxicity and the drug's teratogenicity.
- Other Tx of RP in general is UV sunglasses and brimmed hats
- Excessive light exposure may play a role in retinal degenerations caused by rhodopsin mutations.
The early-onset retinal dystrophies are collectively termed ?
Leber congenital amaurosis (LCA)
3 autosomal dominant and 18 recessive mutations have been identified
Signs and symptoms of LCA?
severely reduced vision from birth, associated with wandering nystagmus.
Va may range from 20/200 to no light perception.
In the early stages, obvious fundus changes are rare.
Later, round, subretinal black-pigmented clumps may develop in some patients.
Some infants with LCA rub or poke their eyes (the oculodigital reflex), as do other infants with poor vision.
Most children with LCA have normal intelligence, and some of the observed psychomotor impairment may be secondary to sensory deprivation.
Cataracts and keratoconus may be present in older children.
ERG response in LCA is ?
Typically minimal or undetectable.
- This lack of response differentiates LCA from dystrophic diseases in which the ERG response diminishes with age and from syndromes with similar clinical presentation, such as albinism, achromatopsia, and CSNB.
- One form of LCA bearing a mutation in RPE65 has been treated successfully by gene therapy in clinical trials by use of an adeno-associated virus. The results of a phase 1 trial showed sustained improvement in 12 patients with RPE65-associated LCA after gene-replacement therapy.
How are cone dystrophies different from congenital color blindness?
The cone dystrophies should not be confused with congenital color blindness, in which there are color deficits for specific colors but no associated retinal degeneration, or with macular dystrophies, in which the defect is confined largely to the central retinal cones.
Patients with congenital color blindness (protanopia, deuteranopia, and tritanopia) have normal visual acuity and do not show signs of progressive disease.
Describe progressive cone dystrophies?
heterogeneous group of diseases with onset in the teenage or later adult years.
In some patients, secondary rod photoreceptor involvement develops in later life, leading to overlap between progressive cone and cone-rod dystrophies.
Cone dystrophies and ERG?
- Cone dystrophies are diagnosed when ERG results indicate an abnormal or undetectable photopic ERG response and a normal or near-normal rod-isolated ERG response.
- When present, the cone flicker ERG response is almost invariably delayed, in keeping with generalized cone system dysfunction.
What is inheritance of cone dystrophies?
All 3 mendelian inheritance patterns are associated with cone dystrophies.
Symptoms of cone dystrophy?
A diagnosis is suggested by the progressive loss of visual acuity and color discrimination, often accompanied by hemeralopia (day blindness) and photophobia (light intolerance).
Peripheral visual fields may remain normal
Signs of cone dystrophy?
Ophthalmoscopy may show a symmetric bull's-eye pattern of macular atrophy (Fig 12-6) or more severe atrophy, such as demarcated circular macular lesions.
Mild to severe temporal optic atrophy and tapetal retinal reflexes (with a glistening greenish or golden sheen) may also be present.
Patients with cone dystrophies may have fundi that appear normal, especially early in the course of their disease, and may be suspected of malingering.
Dominant cone dystrophy linked to 6p21.1 is caused by mutations in the gene coding for ?
guanylate cyclase activator 1A (GUCA1A), a calcium-binding protein expressed in photoreceptor outer segments.
Mutations in GUCY2D at 17p13.1 have been identified in a family with autosomal dominant progressive cone degeneration.
Different mutations of both alleles in the same gene cause autosomal recessive LCA.
- These patients exhibit foveal atrophy that may be misdiagnosed as Stargardt disease, but ERG studies of these patients show the photopic response is severely abnormal, the scotopic response is maintained, and the Goldmann visual field is full.
- An adult-onset, X-linked recessive cone dystrophy with a tapetal-like sheen and Mizuo-Nakamura phenomenon (in which the fundus appearance changes with dark adaptation) has been reported in several pedigrees, but the affected gene has not yet been identified.
Describe findings and mutation in "cone dystrophy with supernormal ERG"?
Related to a mutation in KCNV2
has pathognomonic (diagnostic) ERG findings.
first disorder of the human visual system known to be related to a potassium channel.
The disorder is recessively inherited, and patients usually present with loss of visual acuity.
There are no specific fundus features (there are often nonspecific changes at the macula), and the diagnosis is made by ERG.
Important genes in which mutations are associated with cone-rod degenerations are those for ?
Stargardt disease (ABCA4)
Alström disease (ALMS1)
dominant spinocerebellar ataxia (SCA7).
Dominant cone-rod dystrophy may result from mutations in GUCY2D, whereas recessive mutations cause LCA. Similarly, various mutations in CRX can cause RP, LCA, or cone-rod dystrophy.
Basics of Stargardt disease?
Mostly autosomal recessive
MC juvenile macular dystrophy and a common cause of central vision loss in adults younger than 50 years.
Va typically ranges from 20/50 to 20/200.
Most patients retain fair visual acuity (eg, 20/70-20/100) in at least 1 eye.
Fundus findings in stargardt dz?
juvenile-onset foveal atrophy surrounded by discrete, yellowish, round or pisciform flecks at the level of the RPE (Fig 12-7A).
If the flecks are widely scattered throughout the fundus, the condition is commonly referred to as fundus flavimaculatus.
A clinical diagnosis of Stargardt disease may be confirmed by the finding of a ____ on fluorescein angiography.
- This phenomenon—in which the retinal circulation is highlighted against a hypofluorescent background because of blocking of choroidal fluorescence—is present in at least 80% of patients with the disorder (Fig 12-7B).
Stargardt Fundus autofluorescence imaging may show characteristic findings:
peripapillary sparing of the RPE changes; central macular hypoautofluorescence; and, over time, a radially outward expanding pattern of hyperautofluorescent flecks, which leave hypoautofluorescent flecks in their wake.
The exact findings appear to vary by genotype.
In most patients, the condition is slowly progressive with the accumulation of lipofuscin-like material in the RPE (Fig 12-8).
The differential diagnosis of Stargardt disease includes conditions that may cause a bull's-eye atrophic maculopathy (table)
What vitamin should be avoided in pts with stargardt dz?
Vitamin A supplementation accelerates the accumulation of lipofuscin pigments in the RPE and should be avoided in patients with Stargardt disease.
Recent evidence has shown that ERG recordings play a useful role in prognosis.
What is fundus flavimaculatus?
If the round or pisciform flecks at the level of the RPE in Stargardt dz are widely scattered throughout the fundus.
Stargardt disease is caused by mutations in the ABCA4 gene, which encodes ___?
an ATP-binding cassette (ABC) transporter protein expressed by rod outer segments.
- The gene is very large (50 exons) and has many polymorphisms, and as of 2014 more than 650 disease-causing variants have been identified.
Other, less frequent causes of a similar phenotype include mutations in the dominant genes STGD4 and ELOVL4 (the latter of which encodes a photoreceptor-specific component of the fatty acid elongation system) and mutations in PRPH2.
Best disease inheritance and mutation?
autosomal dominant maculopathy
- caused by mutations in the BEST1 (or VMD2) gene, which is located on the long arm of chromosome 11 and encodes the protein bestrophin.
Where is Bestrophin located?
localizes to the basolateral plasma membrane of the RPE and functions as a transmembrane chloride channel
The resulting lipofuscin accumulation in Best dz may be secondary to abnormal ion flux.
Signs of Best dz?
yellow, egg yolk-like (vitelliform) macular lesion in childhood, which eventually breaks down, leaving a mottled geographic atrophic appearance (Fig 12-9).
Late in the course of the disease, the geographic atrophy may be difficult to distinguish from other types of macular degeneration or dystrophy.
Some patients (up to 30% in some series) have extrafoveal vitelliform lesions in the fundus. However, the macular appearance in all stages is deceptive, as most patients maintain relatively good vision throughout the course of the disease.
Even patients with "scrambled-egg" macular lesions typically have 20/30 visual acuity.
In approximately 20% of patients, a choroidal neovascular membrane develops in 1 eye during the course of the disease and, if untreated, may result in poor vision.
ERG and EOG in Best Dz?
The ERG response is characteristically normal, and the electro-oculogram (EOG) result is always abnormal.
- The light rise of the EOG is typically severely reduced or absent. The EOG abnormality is always present in Best disease and serves as a marker for the disease, even in individuals who are asymptomatic and have normal fundi.
- Rather than attempt an EOG recording in a child with vitelliform lesions, many clinicians perform EOG recordings of the parents to identify the carrier.
- The EOG may be useful in evaluating poorly defined central macular lesions.
What is autosomal recessive bestrophinopathy (ARB) ?
also related to mutation in BEST1
- associated with severe loss of the EOG light rise as well but shows progressive retinal dysfunction on ERG.
Patients with ARB usually present with loss of visual acuity and show diffuse irregularity of the RPE and dispersed punctate flecks, which are distinct from extramacular vitelliform lesions.
adult-onset foveomacular vitelliform dystrophy mutation?
usually caused by mutations in PRPH2
Autosomal dominant inheritance has been recognized in some families.
The EOG patterns in adult-onset foveomacular vitelliform dystrophy?
tend to be normal or only mildly subnormal.
Signs of adult-onset foveomacular vitelliform dystrophy?
characterized by yellow subfoveal lesions that are bilateral, round or oval, and typically one-third disc diameter in size; they often contain a central pigmented spot (Fig 12-10).
Occasionally, the lesions may be larger and misdiagnosed as Best disease or even as age-related macular degeneration.
This dystrophy generally appears in the fourth to sixth decades in patients who either are visually asymptomatic or have mild blurring and metamorphopsia.
Eventually, the lesions may fade, leaving an area of RPE atrophy, but most patients retain reading vision in at least 1 eye throughout their lives.
What is vitelliform exudative macular detachment?
Patients with numerous basal laminar (cuticular) drusen may develop this.(Fig 12-11).
The yellowish subretinal fluid blocks background fluorescence early, often stains late in the angiogram study, and may be mistaken for choroidal neovascularization. Patients with yellowish macular detachments often maintain good visual acuity for many months but may eventually lose central vision because of geographic atrophy or choroidal neovascularization and disciform scarring.
Figure 12-11 A, Color fundus photograph of vitelliform lesion in the setting of numerous cuticular (basal laminar) drusen. B, Corresponding late-phase fluorescein angiography image showing staining of drusen and vitelliform lesion
In some patients with large, soft drusen, there is a large, central coalescence of drusen, or called?
drusenoid RPE detachment, which may occasionally mimic a macular vitelliform lesion (Fig 12-12).
Such lesions often have pigment mottling on their surface and are surrounded by numerous other individual or confluent soft drusen.
They may remain stable (and allow for good vision) for many years, but eventually they tend to flatten and evolve into geographic atrophy.
Describe what "Early-onset (or familial) drusen" is?
typically manifests at younger ages than do those in most cases of age-related macular degeneration.
Drusen are usually numerous and vary in size, typically extending beyond the vascular arcades and nasal to the optic disc (Fig 12-13).
Although early-onset drusen are presumed to be genetically determined, the inheritance pattern in the vast majority of young patients is never established.
early-onset drusen have been classified into 3 entities:
(1) large colloid drusen,
(2) Malattia leventinese
(3) cuticular drusen.
Appearance of large colloid drusen?
On fundus examination, large colloid drusen appear as large, yellowish, and bilateral lesions located in the macula and/or the periphery of the retina.
They are hyperautofluorescent.
Malattia leventinese and Doyne honeycomb dystrophy are 2 phenotypes of the same condition, what is the inheritance?
autosomal dominant drusen.
The condition is caused by an autosomal dominant mutation in the gene EFEMP1, which is located on chromosome 2 and codes for fibulin 3 (also known as epidermal growth factor-containing fibulin-like extracellular matrix protein 1).
The phenotype is distinctive because the drusen often develop in a radiating pattern from the fovea.
Describe The cuticular or basal laminar drusen ?
phenotype is a clinical syndrome that may occur in middle age (Fig 12-14).
Patients with this phenotype may be at greater risk of macular degeneration as they age.
The syndrome involves innumerable, homogeneous, round drusen that are more apparent on angiography than on biomicroscopy and impart a "starry-sky" appearance.
These drusen are associated with a vitelliform macular detachment.
SD-OCT imaging reveals that these sub-RPE drusen have a pointed or conical appearance.
The phenotype is strongly associated with the Tyr402His mutation of the CFH gene.
Other drusenlike deposits that manifest before age 50 include deposits associated with some hereditary dz with basement membrane abnormalities. These disorders include ?
Alport syndrome and membranoproliferative glomerulonephritis type II.
Desribe what is Pattern Dystrophies?
group of disorders characterized by the development, typically in midlife, of various patterns of yellow, orange, or gray pigment deposition at the level of the RPE in the macular area.
Typically autosomal dominant.
Pattern dystrophies may be subdivided into 4 major patterns according to the distribution of pigment deposits:
(1) adult-onset foveomacular vitelliform dystrophy
(2) butterfly-type pattern dystrophy (Fig 12-15),
(3) reticular-type pattern dystrophy (Fig 12-16), and
(4) fundus pulverulentus (coarse pigment mottling).
Note, however, that considerable variation in clinical presentation exists.
The clinical pattern may vary among affected family members, or even between the 2 eyes of a given patient, and it can evolve from 1 pattern to another over time.
The overlapping ophthalmoscopic features of these patterns and their similar clinical implications suggest that they are either closely related or variable expressions of the same genetic defect.
Most forms of autosomal dominant pattern dystrophy have been associated with mutations in ?
The most common presenting symptom of the pattern dystrophies is ?
slightly diminished visual acuity or mild metamorphopsia.
Patients are often asymptomatic, however, and the conditions are identified only upon the discovery of unusual macular lesions during routine ophthalmoscopy.
(3) reticular-type pattern dystrophy (Fig 12-16)
Electrophysiologic testing in pattern dystrophy?
Results of functional and electrophysiologic testing are generally normal, except for a borderline or mildly reduced EOG consistent with a diffuse RPE disorder.
What is the risk of choroidal neovascularization in pattern dystrophy?
The risk of choroidal neovascularization is low, and geographic macular atrophy may develop progressively.
Describe Sorsby macular dystrophy ?
involves the development of bilateral, subfoveal, choroidal neovascular lesions at approximately 40 years of age (Fig 12-17).
As the macular lesions evolve, they take on the appearance of geographic atrophy, with pronounced clumps of black pigmentation around the central ischemic and atrophic zone (a pseudoinflammatory appearance).
An early sign of the disease is the presence of numerous fine drusenlike deposits or a confluent plaque of faintly yellow material beneath the RPE of the posterior pole.
pathogenesis of Sorsby macular dystrophy ?
Histologic specimens show a lipid-containing deposit between the basement membrane of the RPE and the inner collagenous layers of the Bruch membrane that may impede transport and contribute to the pathogenesis.
The gene for Sorsby dystrophy ?
The gene for Sorsby dystrophy, TIMP3 (on chromosome 22), codes for a tissue inhibitor of metalloproteinase, which is involved in extracellular matrix remodeling.
What is Choroideremia ?
X-linked chorioretinal dystrophy characterized by diffuse and progressive degeneration of the RPE and choriocapillaris (Fig 12-18).
Presentation of choroidermia ?
In affected males, the degeneration initially manifests as mottled areas of pigmentation in the anterior equatorial region and macula.
The anterior areas gradually degenerate to confluent scalloped areas of RPE and choriocapillaris loss; larger choroidal vessels are preserved.
Furthermore, the retinal vessels appear normal, and there is no optic atrophy. Patients have night blindness and show progressive peripheral visual field loss over 3-5 decades.
Most patients maintain good visual acuity.
FA in choroidermia?
The fluorescein angiographic changes are pronounced; the scalloped areas of missing choriocapillaris appear hypofluorescent next to brightly hyperfluorescent areas of perfused choriocapillaris.
Fundus autofluorescence shows hypoautofluorescence in the areas of atrophy, as well as a characteristic speckled pattern of autofluorescence in the nonatrophic areas.
ERG in choroidermia?
The ERG response is abnormal early in the course of the disease and is generally extinguished by midlife.
The differential diagnosis of choroideremia includes gyrate atrophy, thioridazine hydrochloride retinal toxicity, and Bietti crystalline dystrophy.
Carriers of choroideremia are usually asymptomatic and have normal ERG signals.
Mutation in choroidermia?
Mutations in CHM, which is located at Xq21.2 and encodes for a geranylgeranyl transferase Rab escort protein.
Histologic studies of choroideremia and studies of the localization of the CHM protein place the basic defect in the RPE, not in the choroid.
Initial results from a phase 1/2 trial have demonstrated vision improvement in 5 of 6 patients treated with gene therapy.
Signs of X-linked choroideremia?
often show patches of subretinal black mottled pigment, and on occasion, older female carriers show a lobular pattern of choriocapillaris and RPE loss.
Describe Gyrate atrophy inheritance and mutation ?
autosomal recessive dystrophy
caused by mutations in the gene for ornithine aminotransferase (OAT), located on chromosome 10.
Pathogenesis of gyrate atrophy ?
The disorder is the result of a tenfold elevation in plasma levels of ornithine, which is toxic to the RPE and choroid.
Clinical findings of gyrate atrophy ?
Patients with gyrate atrophy have hyperpigmented fundi, accompanied by lobular loss of the RPE and choroid.
The finding of generalized hyperpigmentation of the remaining RPE helps distinguish gyrate atrophy clinically from choroideremia.
In the early stages of the disease, patients have large, geographic, peripheral paving-stone-like areas of atrophy of the RPE and choriocapillaris, which gradually coalesce to form a characteristic scalloped border at the junction of normal and abnormal RPE (Fig 12-19).
Symptoms of gyrate atrophy ?
Night blindness usually develops during the first decade of life, and patients experience progressive loss of visual field and visual acuity later in the course of the disease.
How to make Diagnosis of gyrate atrophy?
The clinical diagnosis can be confirmed by findings of elevated serum or plasma ornithine levels; molecular confirmation can be obtained by mutational analysis of OAT.
Describe the clinical findings of central areolar choroidal dystrophy (CACD) ?
Several genetic types of central choroidal dystrophy probably exist, with overlapping clinical features.
All are characterized by demarcated atrophy of the RPE and choriocapillaris in the macula and normal full-field ERG signals; however, there may be differences in onset and progression.
The central atrophic lesions must be distinguished from those of acquired diseases such as toxoplasmosis and, in older patients, from age-related macular degeneration or late stages of other macular dystrophies that may cause a central round or bull's-eye pattern of RPE atrophy (see Table 12-2).
Young patients with CACD exhibit nonspecific mottled depigmentation within the macula that, over time, develops into a round or oval area of sharply demarcated geographic atrophy (Fig 12-20).
Symptoms of central areolar choroidal dystrophy (CACD) ?
Visual acuity typically stabilizes at approximately 20/200.
Associated choroidal neovascularization rarely develops.
Mutation in central areolar choroidal dystrophy (CACD) ?
Several mutations in PRPH2, each affecting an arginine residue, and a mutation in GUCY2D have been reported to cause autosomal dominant CACD.
Clinical findings in North Carolina macular dystrophy ?
begins in infancy with a cluster of peculiar yellowish-white lesions at the level of the RPE in the macula.
These lesions tend to increase in number and become confluent; in some patients, they progress to severely atrophic macular lesions that can appear excavated or staphylomatous (Fig 12-21).
Symptoms of North Carolina macular dystrophy ?
Disease progression appears to stabilize in most patients by the early teenage years, and visual acuity is usually better than anticipated from the ophthalmoscopic appearance, typically ranging from 20/20 to 20/200.
Mutation in North Carolina macular dystrophy ?
The gene responsible for this disease has been mapped to the long arm of chromosome 6.
Describe X-Linked Retinoschisis (XLRS)?
Retinoschisis refers to a splitting of the neurosensory retina.
The phenotype of congenital X-linked retinoschisis (XLRS) is somewhat variable, even within families.
In severe cases with peripheral schisis, there may be extensive areas of inner retinal elevation resembling total or subtotal retinal detachment.
A recent genotype-phenotype correlation study, the largest to date, identified other presenting signs, such as parafoveal white dots, and showed that schisis is occasionally absent on OCT imaging, even in molecularly confirmed disease.
In X-linked retinoschisis, a common diagnostic feature easily observed in pediatric patients, is?
foveal schisis, which appears as small, cystoid spaces and fine radial striae in the central macula (Fig 12-22), and is often best observed on fundus autofluorescence imaging.
Symptoms of X-linked retinoschisis ?
Central vision may initially be quite good, but with time, degeneration occurs and the visual acuity typically decreases to 20/200.
Peripheral retinoschisis is not a constant feature and may occur in up to 50% of affected males.
Where does the splitting occur in X-Linked retinoschisis?
Histologic studies have shown that the splitting in peripheral XLRS occurs in the nerve fiber layer, whereas in degenerative retinoschisis, the level of splitting is variable and usually deeper within the retina
Signs of XLRS?
Pigmentary deposits may develop in peripheral areas destroyed by the disease process, so advanced cases of XLRS can be mistaken for RP.
Boys with XLRS frequently present with vitreous hemorrhages from torn retinal vessels in areas of retinoschisis.
ERG of XLRS ?
The panretinal involvement and inner retinal location of the disease are reflected in the ERG response, which has a negative waveform such that the a-wave is normal or near normal, but the b-wave is reduced.
Negative waveforms of the dark-adapted, bright-flash ERG occur in diseases in which the inner retina is affected and the photoreceptors are generally unaffected (see Table 12-1).
Mutation and pathogenesis in XLRS?
The gene associated with XLRS, RS1, encodes an adhesion protein called retinoschisin, which localizes to all retinal neurons, beginning with ganglion cells in embryonic development.
Presumably, retinoschisin is essential for Müller cell health because mutations in its coding cause Müller cell degeneration.
Müller cells span the layers of the retina; their end plates form the inner limiting membrane, and their distal ends form the outer limiting membrane between inner segments.
Loss of this bridging cellular matrix protein appears to be key to the pathologic changes present in congenital retinoschisis.
Describe enhanced S-cone (or blue-cone) syndrome (ESCS, where "S" refers to short wavelength)?
is related to the Goldmann-Favre syndrome.
Its most prominent features include night blindness, increased sensitivity to blue light, pigmentary retinal degeneration, an optically empty vitreous, pathognomonic ERG abnormalities, and varying degrees of peripheral to midperipheral visual field loss.
Clinical signs of enhanced S-cone (or blue-cone) syndrome ?
The posterior pole may show round, yellow, sheenlike lesions along the arcades, accompanied by areas of diffuse degeneration.
Deep nummular pigmentary deposition is usually observed at the level of the RPE around the vascular arcades; their presence may lead to an incorrect diagnosis of "atypical" RP.
Macular (and sometimes peripheral) schisis may be present.
ERG of enhanced S-cone (or blue-cone) syndrome ?
The ERG response includes no detectable dim-flash, rod-specific signal; delayed and simplified responses to a brighter flash that have the same waveform under both dark-adapted and light-adapted conditions; and a flicker ERG response of lower amplitude than that of the single-flash photopic a-wave.
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