Electroretinography

Principles

The electroretinogram (ERG) is the record of an action potential produced by the retina when it is stimulated by light of adequate intensity. The recording is made between an active electrode either in contact with the cornea or a skin electrode placed just below the lower eyelid margin, and a reference electrode on the forehead. The potential between the two electrodes is then amplified and displayed (Fig. 15.1). The normal ERG is biphasic (Fig. 15.2).

1 The a-wave is the initial fast negative deflection generated by photoreceptors.

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2 The b-wave is the next slower positive large amplitude deflection. Although it is generated from fluxes of potassium ions within and surrounding Müller cells, it is directly dependent on functional photoreceptors and its magnitude makes it a convenient measure of photoreceptor integrity. The amplitude of the b-wave is measured from the trough of the a-wave to the peak of the b-wave. It is enhanced with dark adaptation and increased light stimulus. The b-wave consists of b-1 and b-2 subcomponents; the former probably represents both rod and cone activity and the latter mainly cone activity. It is possible to single out rod and cone responses with special techniques.

Fig. 15.1 Principles of electroretinography

Fig. 15.2 Components and origins of the electroretinogram

Standard ERG

The normal ERG consists of five recordings (Fig. 15.3). The first three are elicited after 30 minutes of dark adaptation (scotopic), and the last two after 10 minutes of adaptation to moderately bright diffuse illumination (photopic). It may be difficult to dark adapt children for 30 minutes and therefore dim light (mesopic) conditions can be utilized to evoke predominantly rod-mediated responses to low intensity white or blue light stimuli.

1 Scotopic ERG

a Rod responses are elicited with a very dim flash of white or blue light, resulting in a large b-wave and a small or non-recordable a-wave.

b Combined rod and cone responses are elicited with a very bright white flash, resulting in a prominent a-wave and b-wave.

c Oscillatory potentials are elicited by using a bright flash and changing the recording parameters. The oscillatory wavelets occur on the ascending limb of the b-wave and are generated by cells in the inner retina.

2 Photopic ERG

a Cone responses are elicited with a single bright flash, resulting in an a-wave and a b-wave with small oscillations.

b Cone flicker is used to isolate cones by using a flickering light stimulus at a frequency of 30 Hz to which rods cannot respond. It provides a measure of the amplitude and implicit time of the cone b-wave. Cone responses can be elicited in normal eyes up to 50 Hz, after which point individual responses are no longer recordable (‘critical flicker fusion’).

Fig. 15.3 Normal electroretinographic recordings

Multifocal ERG

Multifocal ERG is a method of producing topographical maps of retinal function (Fig. 15.4). The stimulus is scaled for variation in photoreceptor density across the retina. At the fovea, where the density of receptors is high, a lesser stimulus is used than in the periphery where receptor density is lower. As with conventional ERG, many types of measurements can be made. Both the amplitude and timing of the troughs and peaks can be measured and reported and the information can be summarized in the form of a three-dimensional plot which resembles the hill of vision. The technique can be used for almost any disorder which affects retinal function.

Fig. 15.4 Multifocal electroretinogram

Electro-oculography

Fig. 15.5 Principles of electro-oculography

Dark adaptometry

Fig. 15.6 Dark adaptation curve

Colour vision tests

Colour vision (CV) testing is sometimes useful in the clinical evaluation of hereditary fundus dystrophies, where dyschromatopsia may be present prior to the development of impairment of visual acuity and visual field loss.

Colour vision tests

1 Ishihara test is used mainly to screen for congenital protan and deuteran defects. It consists of a test plate followed by sixteen plates each with a matrix of dots arranged to show a central shape or number which the subject is asked to identify (Fig. 15.7A). A colour deficient person will only be able to identify some of the figures. Inability to identify the test plate (provided visual acuity is sufficient) indicates non-organic visual loss.

2 Hardy–Rand–Rittler is similar to Ishihara but more sensitive since it can detect all three congenital colour defects (Fig. 15.7B).

3 City University test consists of 10 plates each containing a central colour and four peripheral colours (Fig. 15.7C). The subject selects the peripheral colours which most closely matches the central colour.

4 Farnsworth–Munsell 100-hue is the most sensitive for both congenital and acquired colour defects but is seldom used in clinical practice. Despite the name it consists of 85 hue caps contained in four separate racks in each of which the two end caps are fixed while the others are loose so they can be randomized by the examiner (Fig. 15.7D).

a The subject is asked to rearrange the loose randomized caps ‘in their natural’ order in one box.

b The box is then closed, turned upside down and then opened so that the markers on the inside of the caps become visible.

c The findings are then recorded in a simple cumulative manner on a circular chart.

d Each of the three forms of dichromatism is characterized by failure in a specific meridian of the chart (Fig. 15.8).

5 Farnsworth D15 hue discrimination test is similar to the Farnsworth–Munsell 100-hue test but utilizes only 15 caps.

Fig. 15.7 Colour vision tests. (A) Ishihara; (B) Hardy–Rand–Rittler; (C) City University; (D) Farnsworth-Munsell 100-hue test

(Courtesy of T Waggoner – fig. B)

Fig. 15.8 Farnsworth–Munsell test results of colour deficiencies. (A) Protan; (B) deuteran; (C) tritan

Typical retinitis pigmentosa

Retinitis pigmentosa (RP) defines a clinically and genetically diverse group of diffuse retinal dystrophies initially predominantly affecting the rod photoreceptor cells with subsequent degeneration of cones (rod-cone dystrophy). It is the most commonly encountered hereditary fundus dystrophy with a prevalence of approximately 1 : 5000.

Inheritance

The age of onset, rate of progression, eventual visual loss and associated ocular features are frequently related to the mode of inheritance. RP may occur as an isolated sporadic disorder, or be inherited as AD, AR or XL. Many cases are due to mutation of the rhodopsin gene. XL is the least common but most severe form and may result in complete blindness by the third or fourth decades. Female carriers may have normal fundi or show a golden-metallic (’tapetal’) reflex at the macula (Fig. 15.9A) and/or small peripheral patches of bone-spicule pigmentation (Fig. 15.9B). RP, often atypical, may also be associated with systemic disorders which are usually AR (see below).

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Fig. 15.9 Findings in carriers of XL retinitis pigmentosa. (A) ‘Tapetal’ reflex at the macula; (B) mild peripheral pigmentary changes

(Courtesy of D Taylor and CS Hoyt, from Pediatric Ophthalmology and Strabismus, Elsevier, Saunders, 2005 – fig. A)

Diagnosis

The diagnostic criteria for RP comprise bilateral involvement, with loss of peripheral and night vision. The classical triad of RP is: (a) arteriolar attenuation, (b) retinal bone-spicule pigmentation and (c) waxy disc pallor.

1 Presentation is with nyctalopia, often during the 2nd–3rd decades, though may be earlier or later, depending on the pedigree.

2 Signs in chronological order:

• Subtle mid-peripheral RPE atrophy associated with mild arteriolar narrowing, and mid-peripheral intraretinal perivascular ‘bone-spicule’ pigmentary changes (Fig. 15.10A).

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• Gradual increase in density of the pigmentary changes with anterior and posterior spread (Fig. 15.10B).

• Tessellated fundus appearance, due to RPE atrophy and unmasking of large choroidal vessels (Fig. 15.10C).

• Severe arteriolar narrowing and gliotic ‘waxy pallor’ of the optic discs (Fig. 15.10D).

• The macula may show atrophy, epiretinal membrane formation and CMO; the latter may respond to systemic acetazolamide.

3 ERG in early disease shows reduced scotopic rod and combined responses (Fig. 15.11); later photopic responses become reduced and eventually the ERG becomes extinguished.

4 EOG is subnormal with an absence of the light rise.

5 DA is prolonged and may be useful in early cases where the diagnosis is uncertain.

6 Perimetry initially demonstrates small mid-peripheral scotomas that gradually coalesce to form the classical annular scotoma, which expands both peripherally and centrally. It ultimately leaves a tiny island of central vision which may eventually be extinguished. Perimetry is useful in monitoring the progression of disease.

7 Prognosis is variable and tends to be associated with the mode of inheritance as follows:

• XL disease has the worst prognosis with severe visual loss by the 4th decade.

• AR disease and sporadic cases have a more favourable prognosis with retention of central vision until the 5th–6th decade or later.

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• AD disease generally has the best prognosis with retention of central vision beyond the 6th decade.

Fig. 15.10 Progression of retinitis pigmentosa. (A) Early changes; (B) advanced changes; (C) unmasking of choroidal vessels; (D) end-stage disease

(Courtesy of P Saine – fig. A)

Fig. 15.11 ERG in early retinitis pigmentosa shows reduced scotopic rod and combined responses

Ocular associations

Regular follow-up of patients with RP is essential to detect other vision-threatening complications, some of which may be amenable to treatment.

1 Posterior subcapsular cataracts are common in all forms of RP; surgery is often beneficial.

2 Open-angle glaucoma occurs in 3% of cases.

3 Myopia is common.

4 Keratoconus is uncommon.

5 Vitreous changes, which are common, consist of posterior vitreous detachment and occasionally intermediate uveitis.

6 Optic disc drusen occur more frequently in patients with RP.

7 Coats-like disease with lipid deposition in the peripheral retina and exudative retinal detachment (Fig. 15.12) may occasionally develop in adult life.

Fig. 15.12 Coats-like features associated with retinitis pigmentosa

Atypical retinitis pigmentosa

Atypical RP describes conditions that are closely related to typical RP or represent incomplete forms of the disease.

Fig. 15.13 Atypical retinitis pigmentosa. (A) Sine pigmento; (B) retinitis punctata albescens; (C) sector

Important systemic associations

Refsum disease

1 Inheritance is AR. The infantile and adult forms are genetically distinct.

2 Pathogenesis. Deficiency in phytanic acid alpha-hydrolase results in accumulation of phytanic acid throughout the body. Early detection and treatment with a diet low in phytanic acid can arrest disease progression.

3 Systemic features

a Infantile disease is characterized by dysmorphic facies, mental handicap, hepatomegaly and deafness.

b Adult disease is characterized by cerebellar ataxia, polyneuropathy, anosmia, deafness, cardiomyopathy and ichthyosis (Fig. 15.14B).

4 Fundus appearance may be similar to RP or merely show salt-and-pepper changes.

5 Other ocular features include cataract, prominent corneal nerves, optic atrophy, nystagmus and poorly dilating pupils.

Fig. 15.14 Selected systemic associations of retinitis pigmentosa. (A) Acanthocytosis in Bassen–Kornzweig syndrome; (B) ichthyosis in adult Refsum disease; (C) ptosis in Kearns–Sayre syndrome; (D) polydactyly in Bardet–Biedl syndrome

Progressive cone dystrophy

Progressive cone dystrophy predominantly affects the cone system. In some cases there is no evidence of rod dysfunction whilst in others rod dysfunction subsequently develops but cone deficiency still predominates (cone-rod dystrophy).

Fig. 15.15 Progressive cone dystrophy. (A) Early pigment mottling; (B) Golden sheen in XL disease; (C) ‘bull’s eye’ maculopathy; (D) geographic atrophy

(Courtesy of Moorfields Eye Hospital – fig. A)

Table 15.1 Other causes of bull’s eye macula

Fig. 15.16 ERG in progressive cone dystrophy shows reduced photopic responses and flicker fusion frequency

Fig. 15.17 Bull’s eye maculopathy. (A and B) Clinical appearance; (C and D) appearance on FA

Leber congenital amaurosis

Leber congenital amaurosis is a severe rod-cone dystrophy that is the commonest genetic cause of visual impairment in infants and children. It carries a very poor prognosis.

Fig. 15.18 Leber congenital amaurosis. (A) Mild pigmentary retinopathy; (B) macular pigmentation and optic disc drusen; (C) macular coloboma-like atrophy; (D) oculodigital syndrome

(Courtesy of A Moore – figs A-C; N Rogers – fig. D)

Stargardt disease and fundus flavimaculatus

Stargardt disease (juvenile macular dystrophy) and fundus flavimaculatus (FFM) are regarded as variants of the same disease despite presenting at different times and carrying different prognoses. The condition is characterized by diffuse accumulation of lipofuscin within the RPE that results in vermilion fundus and a ‘dark choroid’ seen on FA (see below).

Fig. 15.19 Stargardt disease/fundus flavimaculatus. (A) Nonspecific macular mottling; (B) ‘snail slime’ maculopathy surrounded by flecks; (C) bull’s eye maculopathy surrounded by flecks; (D) diffuse flecks

Fig. 15.20 Imaging in Stargardt disease/fundus flavimaculatus. (A) FA shows macular hyperfluorescence and a ‘dark’ choroid; (B) FA shows hyperfluorescent spots; (C) ICGA shows hypofluorescent spots

(Courtesy of A Bolton – fig. C)

Bietti corneoretinal crystalline dystrophy

Bietti dystrophy is characterized by deposition of crystals in the retina and the superficial peripheral cornea. It is much more common in East Asians, particularly Chinese, than other ethnicities.

Fig. 15.21 (A) Bietti corneoretinal crystalline dystrophy; (B) FA shows hypofluorescent patches

Alport syndrome

Fig. 15.22 Alport syndrome. (A) Perimacular flecks; (B) peripheral flecks

(Courtesy of J Govan)

Familial benign fleck retina

Familial benign fleck retina is a very rare disorder which is asymptomatic and therefore usually discovered by chance.

Fig. 15.23 Benign familial fleck retina

Pigmented paravenous chorioretinal atrophy

Paravenous chorioretinal atrophy is an innocuous and asymptomatic condition that is usually non-progressive. The fundus changes are bilaterally symmetric.

Fig. 15.24 Pigmented paravenous retinochoroidal atrophy

(Courtesy of C Barry)

Congenital stationary night blindness

Congenital stationary night blindness (CSNB) refers to a group of disorders characterized by infantile onset nyctalopia and non-progressive retinal dysfunction. The fundus appearance may be normal or abnormal.

With abnormal fundus

1 Oguchi disease is a very rare AR condition.

• The fundus has an unusual golden-yellow colour in the light-adapted state (Fig. 15.25A) which becomes normal after prolonged dark adaptation (Mizuo phenomenon – Fig 15.25B).

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• Rod function is absent after 30 minutes of dark adaptation but recovers to a near-normal level after a long period of dark adaptation.

2 Fundus albipunctatus is an innocuous AR or AD condition.

• The fundus shows a multitude of subtle, tiny yellow-white spots at the posterior pole, sparing the fovea and extending to the periphery (Fig. 15.26A).

• The retinal blood vessels, optic disc, peripheral fields and visual acuity remain normal.

• FA shows mottled hyperfluorescence, except at the fovea, indicating depigmentation of the RPE (Fig. 15.26B).

Fig. 15.25 Mizuo phenomenon in Oguchi disease. (A) In the light-adapted state; (B) in the dark-adapted state

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

Fig. 15.26 Fundus albipunctatus. (A) Clinical appearance; (B) FA shows mottled hyperfluorescence

(Courtesy of C Barry)

Congenital monochromatism (achromatopsia)

Juvenile Best macular dystrophy

Best (vitelliform) macular dystrophy is the second most common macular dystrophy.

Fig. 15.27 Juvenile Best macular dystrophy. (A) Vitelliform stage; (B) FA shows hypofluorescence due to blocked background choroidal fluorescence; (C) OCT shows material within the RPE; (D) multifocal disease; (E) pseudohypopyon stage; (F) vitelliruptive stage

(Courtesy of C Barry – fig. C)

Multifocal vitelliform lesions without Best disease

Occasionally multifocal vitelliform lesions (Fig. 15.28), identical to those in Best disease, may become manifest in adult life and give rise to diagnostic problems. However, in these patients the EOG is normal and the family history is negative. Occasionally Best dystrophy may present with multifocal lesions.

Fig. 15.28 Multifocal vitelliform lesions

(Courtesy of C Barry)

Pattern dystrophy

Pattern dystrophy is a generic term that encompasses several retinal dystrophies exhibiting yellow, orange or grey deposits at the macula that have a variety of morphologies. The lesions are associated with the accumulation of lipofuscin at the level of the RPE. Pattern dystrophy is usually present in isolation but has also been described in patients with myotonic dystrophy, Kjellin syndrome (spastic paraplegia and dementia) and pseudoxanthoma elasticum. The main phenotypes having the following common characteristics are discussed below: (a) AD inheritance, (b) variable expressivity, (c) bilateral symmetrical involvement, (d) relatively benign course and (e) normal ERG but occasionally abnormal EOG.

Adult-onset macular vitelliform dystrophy

In contrast to juvenile Best disease, the foveal lesions are smaller, present later and do not demonstrate similar evolutionary changes.

1 Inheritance. It is caused by mutation in the RDS gene on chromosome 6p, as well as the BEST1 gene in common with juvenile-onset Best dystrophy.

2 Presentation is in the 4th–6th decades with mild to moderate decrease in visual acuity and sometimes metamorphopsia although often the condition is discovered by chance.

3 Signs

• Bilateral, symmetrical, round or oval, slightly elevated yellowish subfoveal deposit, about one-third of a disc diameter in size, often centered by a pigmented spot (Fig. 15.29A).

• Associated macular drusen may be seen in some cases.

4 FA shows central hypofluorescence surrounded by a small irregular hyperfluorescent ring (Fig. 15.29B).

Fig. 15.29 (A) Adult-onset macular vitelliform dystrophy; (B) FA shows corresponding hyperfluorescence

Butterfly-shaped macular dystrophy

1 Inheritance is AD.

2 Presentation is in the 2nd–3rd decades usually by chance and occasionally with mild impairment of central vision.

3 Signs

• Yellow pigment at the fovea arranged in a triradiate manner (Fig. 15.30A).

• Peripheral pigmentary stippling may be present.

• Atrophic maculopathy may occasionally develop with time.

4 FA shows non-fluorescence of the lesions outlined by hyperfluorescence (Fig. 15.30B).

Fig. 15.30 (A) Butterfly dystrophy; (B) FA shows non-fluorescence of the lesion outlined by hyperfluorescence

(Courtesy of Moorfields Eye Hospital)

Multifocal pattern dystrophy simulating fundus flavimaculatus

1 Presentation is in the 4th decade with mild impairment of central vision.

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2 Signs multiple, widely-scattered, irregular, yellow lesions that may be similar to those seen in fundus flavimaculatus (Fig. 15.31A).

3 FA shows hyperfluorescence of flecks but the choroid is not dark (Fig. 15.31B).

Fig. 15.31 (A) Multifocal pattern dystrophy simulating fundus flavimaculatus; (B) FA shows hyperfluorescence but the choroid is not dark

(Courtesy of S Milewski)

Macroreticular pattern dystrophy

1 Presentation is in early childhood.

2 Signs

• Initially pigment granules at the fovea.

• Reticular pigmentation develops that spreads to the periphery.

3 FA enhances the characteristic macular changes (Fig. 15.32).

Fig. 15.32 FA of macroreticular pattern dystrophy

(Courtesy of RF Spaide, from Diseases of the Retina and Vitreous, WB Saunders, 1999)

North Carolina macular dystrophy

North Carolina macular dystrophy is a very rare non-progressive condition. It was first described in families living in the mountains of North Carolina and subsequently in many unrelated families in other parts of the world.

Fig. 15.33 North Carolina macular dystrophy. (A) Peripheral flecks; (B) confluent macular flecks; (C) early neovascular maculopathy; (D) coloboma-like macular lesion

(Courtesy of P Morse)

Familial dominant drusen

Familial drusen (Doyne honeycomb choroiditis, malattia leventinese) is thought to represent an early-onset variant of age-related macular degeneration.

Fig. 15.34 (A) Familial dominant drusen; (B) with RPE degeneration

(Courtesy of Moorfields Eye Hospital)

Fig. 15.35 Familial dominant drusen. (A and B) FA shows more numerous lesions than seen clinically (C and D)

(Courtesy of C Barry)

Sorsby pseudoinflammatory dystrophy

Sorsby pseudoinflammatory macular dystrophy, also referred to as hereditary haemorrhagic macular dystrophy, is a very rare condition that results in bilateral visual loss in the 5th decade of life.

Fig. 15.36 Sorsby pseudoinflammatory macular dystrophy. (A) Confluent flecks nasal to the disc; (B) exudative maculopathy; (C) subretinal scarring in end-stage disease

(Courtesy of Moorfields Eye Hospital – fig. B)

Benign concentric annular macular dystrophy

Central areolar choroidal dystrophy

Fig. 15.37 Progression of central areolar choroidal dystrophy. (A) Early; (B) intermediate; (C) end-stage

Dominant cystoid macular oedema

Sjögren–Larsson syndrome

Sjögren–Larsson syndrome is a neurocutaneous disorder characterized by congenital ichthyosis, spasticity, convulsions and mental handicap with reduced life expectancy. The basic metabolic defect is deficient activity of fatty aldehyde dehydrogenase.

Fig. 15.38 Macular crystals in Sjögren–Larsson syndrome

(Courtesy of D Taylor and C S Hoyt, from Pediatric Ophthalmology and Strabismus, Elsevier Saunders 2005)

Familial internal limiting membrane dystrophy

Fig. 15.39 Familial internal limiting membrane dystrophy

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

Choroideremia

Choroideremia is a progressive, diffuse degeneration of the choroid, RPE and retinal photoreceptors.

Fig. 15.40 Choroideremia. (A) Female carrier; (B) advanced disease; (C) end-stage disease; (D) FA shows an intact fovea

(Courtesy of K Nischal – fig. B; S Milewski – figs C and D)

Gyrate atrophy

Gyrate atrophy is a metabolic disorder caused by a mutation of the gene encoding the main ornithine degradation enzyme, ornithine aminotransferase. Deficiency of the enzyme leads to elevated ornithine levels in the plasma, urine, CSF and aqueous humour.

Fig. 15.41 Gyrate atrophy. (A) Early disease; (B) advanced disease; (C) end-stage disease with preservation of the fovea

Generalized choroidal dystrophy

Fig. 15.42 Generalized choroidal dystrophy

Progressive bifocal chorioretinal atrophy

Fig. 15.43 Progressive bifocal chorioretinal atrophy

(Courtesy of Moorfields Eye Hospital)

Juvenile X-linked retinoschisis

Diagnosis

1 Inheritance is XL with the implicated gene designated RS1 on Xp22.1-22.2.

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2 Presentation is between the ages of 5–10 years with reading difficulties due to maculopathy. Less frequently the disease presents in infancy with squint or nystagmus associated with advanced peripheral retinoschisis, often with vitreous haemorrhage.

3 Foveal schisis

• ‘Bicycle wheel’ radial striae radiating from the foveola associated with cystoid macular changes (Fig. 15.44A).

• Over time the striae become less evident leaving a blunted foveal reflex.

4 Peripheral schisis predominantly involves the inferotemporal quadrant. It does not extend but may undergo the following secondary changes:

• The inner layer, which consists only of the internal limiting membrane and the retinal nerve fibre layer, may develop oval defects (Fig. 15.44B).

• In extreme cases, the defects coalesce, leaving only retinal blood vessels floating in the vitreous (‘vitreous veils’) (Fig. 15.44C).

• Peripheral silver dendritic figures (Fig. 15.44D), vascular sheathing and pigmentary changes are common.

• Nasal dragging of retinal vessels and retinal flecks may be seen.

5 Complications include vitreous and intra-schisis haemorrhage, neovascularization, subretinal exudation (Fig. 15.45A), and rarely retinal detachment and traumatic rupture of foveal schisis (Fig. 15.45B).

6 Prognosis is poor due to progressive maculopathy. Visual acuity deteriorates during the first two decades and may remain stable until the 5th–6th decades when further deterioration occurs.

7 OCT is useful for documenting progression of maculopathy (Fig. 15.46).

8 ERG is normal in eyes with isolated maculopathy. Eyes with peripheral schisis show a characteristic selective decrease in amplitude of the b-wave as compared with the a-wave on scotopic and photopic testing (Fig. 15.47).

9 EOG is normal in eyes with isolated maculopathy but subnormal in eyes with advanced peripheral lesions.

10 FA of maculopathy may show mild window defects but no leakage.

Fig. 15.44 Juvenile retinoschisis. (A) ‘Bicycle wheel’-like maculopathy; (B) inner leaf defect; (C) ‘vitreous veils’; (D) peripheral dendritic lesions

(Courtesy of K Slowinski – fig. A; C Barry – figs B and C; Moorfields Eye Hospital – fig. D)

Fig. 15.45 Complications of juvenile retinoschisis. (A) Traumatic hole in macular schisis; (B) subretinal exudation

(Courtesy of K Slowinski – fig. A; G-M Sarra – fig. B)

Fig. 15.46 OCT of macular schisis shows cyst-like changes

(Courtesy of J Talks)

Fig. 15.47 ERG in peripheral juvenile retinoschisis shows selective decrease of the b-wave amplitude

Stickler syndrome

Stickler syndrome (hereditary arthro-ophthalmopathy) is a disorder of collagen connective tissue. Inheritance is AD with complete penetrance but variable expressivity. Stickler syndrome is the commonest inherited cause of retinal detachment in children.

Systemic features

1 Facial anomalies include mid-facial hypoplasia, depressed nasal bridge, short nose, anteverted nares and micrognathia (Fig. 15.48A).

2 Oral anomalies include cleft and high-arched palate (Fig. 15.48B), and bifid uvula.

3 Skeletal involvement includes relatively mild spondyloepiphyseal dysplasia, and joint hypermobility that decreases with age but may be followed by osteoarthritis in the 3rd–4th decades. Occasional findings include slender extremities with arachnodactyly that must not be confused with Marfan syndrome.

4 Deafness that may be caused by recurrent otitis media or due to sensorineural defect.

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Fig. 15.48 Stickler syndrome. (A) Facial appearance; (B) cleft and high-arched palate

(Courtesy of K Nischal – fig. B)

Ocular features

1 Presentation is in early childhood with high non-progressive myopia.

2 Signs

• In STL1 patients exhibit an optically empty vitreous, a retrolenticular membrane and circumferential equatorial membranes that extend a short way into the vitreous cavity (membranous type 1 vitreous – Fig. 15.49A).

• In STL2 patients the vitreous has a fibrillary and beaded appearance (fibrillary type 2 vitreous).

• Radial lattice-like degeneration associated with RPE hyperplasia, vascular sheathing and sclerosis (Fig. 15.49B).

• Retinal detachment develops in approximately 50% in the first decade of life, often as a result of multiple or giant tears that may involve both eyes.

• Regular screening is mandatory so that retinal breaks can be treated prophylactically.

3 Associations

a Presenile cataract characterized by frequently non-progressive peripheral cortical ‘wedge’ or ‘fleck’ opacities is common.

b Ectopia lentis is uncommon.

c Glaucoma occurs in 5–10% of cases and is associated with a congenital angle anomaly.

Fig. 15.49 Stickler syndrome. (A) Vitreous liquefaction and membranes; (B) radial lattice degeneration and pigmentary changes

Wagner syndrome

Wagner syndrome (erosive vitreoretinopathy) shows similar vitreous changes to Stickler syndrome but is not associated with systemic abnormalities.

Fig. 15.50 Wagner syndrome. (A) Vitreous liquefaction; (B) peripheral chorioretinal atrophy and preretinal membranes; (C) progressive chorioretinal atrophy; (D) FA shows gross loss of the choriocapillaris

(Courtesy of E Messmer)

Familial exudative vitreoretinopathy

Familial exudative vitreoretinopathy (Criswick–Schepens syndrome) is a slowly-progressive condition characterized by failure of vascularization of the temporal retinal periphery, similar to that seen in retinopathy of prematurity, but not associated with low birth weight and prematurity.

Fig. 15.51 Familial exudative vitreoretinopathy. (A) Peripheral telangiectasia; (B) fibrovascular ridge; (C) fibrovascular proliferation; (D) ‘dragging’ of the disc and macula; (E) subretinal exudation; (F) FA shows vascular straightening and abrupt termination

(Courtesy of C Hoyng – fig. E)

Enhanced S-cone syndrome and Goldmann–Favre syndrome

There appears to be an overlap between these two conditions, and it is believed that the latter may represent a more severe variant of the former.

Fig. 15.52 Enhanced S-cone and Goldmann–Favre syndrome. (A) Severe pigment clumping; (B) macular schisis and pigmentary changes along the arcade

(Courtesy of D Taylor and CS Hoyt, from Pediatric Ophthalmology and Strabismus, Elsevier Saunders 2005 – fig. A; J Donald M Gass, from Stereoscopic Atlas of Macular Diseases, Mosby 1997 – fig. B)

Snowflake vitreoretinal degeneration

Fig. 15.53 Snowflake degeneration

Dominant neovascular inflammatory vitreoretinopathy

Dominant vitreoretinochoroidopathy

Kniest dysplasia

Introduction

Albinism is a genetically determined, heterogeneous group of disorders of melanin synthesis in which either the eyes alone (ocular albinism) or the eyes, skin and hair (oculocutaneous albinism) may be affected. The latter may be either tyrosinase-positive or tyrosinase-negative. The different mutations are thought to act through a common pathway involving reduced melanin synthesis in the eye during development. Tyrosinase activity is assessed by using the hair bulb incubation test, which is reliable only after 5 years of age. Patients with albinism have an increased risk of cutaneous basal cell and squamous cell carcinoma that usually occurs before the fourth decade.

Tyrosinase-negative oculocutaneous albinism

Tyrosinase-negative (complete) albinos are incapable of synthesizing melanin and have white hair and very pale skin (Fig. 15.54A) throughout life with lack of melanin pigment in all ocular structures.

Fig. 15.54 Tyrosinase-negative oculocutaneous albinism. (A) White hair and very pale skin; (B) marked iris translucency; (C) ‘pink eye’ appearance; (D) severe fundus hypopigmentation and foveal aplasia

(Courtesy of L Merin – fig. D)

Tyrosinase-positive oculocutaneous albinism

Tyrosinase-positive (incomplete) albinos synthesize variable amounts of melanin. The hair may be white, yellow or red and darkens with age. Skin colour is very pale at birth but usually darkens by 2 years of age (Fig. 15.55A).

Fig. 15.55 Tyrosinase-positive oculocutaneous albinism. (A) Fair hair and normal skin colour; (B) mild fundus hypopigmentation

(Courtesy of B Majol – fig. A)

Associated systemic syndromes

1 Chediak–Higashi syndrome

• Inheritance is AR with the gene locus on 1q42.

• Mild oculocutaneous albinism.

• Leucocytic abnormalities resulting in recurrent pyogenic infections.

• The vast majority of patients eventually develop a lymphoproliferative syndrome (accelerated phase) characterized by fever, jaundice, hepatosplenomegaly, pancytopenia and bleeding that requires bone marrow transplantation.

• Prognosis for life is generally poor with demise in the 2nd decade.

2 Hermansky–Pudlak syndrome is a lysosomal storage disease of the reticuloendothelial system.

• Inheritance is AR.

• Mild oculocutaneous albinism.

• Platelet dysfunction resulting in early bruising.

• Pulmonary fibrosis, granulomatous colitis and renal failure in some cases.

3 Waardenburg syndrome is an AD condition of which there are four types.

• The main systemic features are white forelock, cutaneous hypopigmentation, poliosis, sensorineural deafness (particularly in type 2), and synophrys or an unusual hair distribution. Upper limb defects, flexion contractures and syndactyly in type 3 and neurological anomalies in type 4.

• Ocular features include lateral displacement of the medial canthi (not present in type 2), broad nasal bridge, hypochromic irides with segmental or total heterochromia (Fig. 15.56), and segmental or total choroidal depigmentation.

Fig. 15.56 Waardenburg syndrome with iris heterochromia and synophrys

Ocular albinism

Involvement is predominantly ocular with normal skin and hair although occasionally hypopigmented skin macules may be seen.

Fig. 15.57 Carrier of XL ocular albinism

Pathogenesis

A cherry-red spot at the macula (Fig. 15.58) is a clinical sign seen in the context of thickening and loss of transparency of the retina at the posterior pole. The fovea, being the thinnest part of the retina and devoid of ganglion cells, retains relative transparency, allowing persistent transmission of the underlying highly vascular choroidal hue. This striking lesion occurs in the sphingolipidoses, which comprise a group of rare inherited metabolic diseases characterized by the progressive intracellular accretion of excessive quantities of certain glycolipids and phospholipids in various tissues of the body, including the retina. The lipids accumulate in the ganglion cell layer of the retina, giving the retina a white appearance. As ganglion cells are absent at the foveola, this area retains relative transparency and contrasts with the surrounding opaque retina. With the passage of time the ganglion cells die and the spot becomes less evident. The late stage of the disease is characterized by degeneration of the retinal nerve fibre layer and consecutive optic atrophy. The following diseases are associated with a cherry-red spot.

Fig. 15.58 Cherry-red spot at the macula

GM1 gangliosidosis (generalized)

Mucolipidosis type I (sialidosis)

GM2 gangliosidosis

Niemann–Pick disease

There are three main types of Niemann disease (A–C) but only the first two are associated with a cherry-red spot. The main ocular features of type C (chronic neuropathic) are gaze palsy and abnormal eye movements.

Farber disease