General

The hereditary fundus dystrophies are a group of disorders that commonly exert their major effect on the retinal pigment epithelium (RPE)–photoreceptor complex and the choriocapillaris to cause a range of visual impairment; the most common group of dystrophies is retinitis pigmentosa. Some dystrophies manifest in early childhood, others do not present until later in life. Isolated dystrophies have features confined to the eye, whilst syndromic dystrophies are part of a wider disease process that also affects tissues elsewhere in the body. Treatments such as gene therapy are being actively investigated, but are unlikely to be available imminently.

Anatomy

There are two types of retinal photoreceptor:

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  The rods are the most numerous (120 million) and are of the densest concentration in the mid-peripheral retina. They are most sensitive in dim illumination and are responsible for night, motion sense and peripheral vision. If rod dysfunction occurs earlier or is more severe than cone dysfunction, it will result in poor night vision (nyctalopia) and peripheral field loss, the former usually occurring first.

  
  
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  The cones are far fewer in number (6 million) and are concentrated at the fovea. They are most sensitive in bright light, and mediate day vision, colour vision, central and fine vision. Cone dysfunction therefore results in poor central vision, impairment of colour vision (dyschromatopsia) and occasionally problems with day vision (hemeralopia).

Inheritance

Most dystrophies are inherited, but sometimes a new mutation (allelic variant) can occur in an individual, and can subsequently be passed to future generations.

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  Autosomal dominant (AD) dystrophies often exhibit variable expressivity, and tend to have a later onset and milder course than recessive disorders.

  
  
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  Recessive dystrophies may be autosomal (AR) or X-linked (XLR). They generally have an earlier onset and a more severe course than AD conditions. In some cases female carriers of XLR conditions show characteristic fundus findings.

  
  
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  X-linked dominant (XLD) conditions are very rare; they are typically lethal in boys (e.g. Aicardi syndrome).

  
  
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  Mitochondrial DNA is inherited solely via the maternal line; retinal dystrophies associated with mitochondrial DNA variants are extremely rare and occur as part of a wider systemic disease. A maternal carrier will usually possess a mixture of mitochondria, only some of which contain the dysfunctional gene, and the presence and severity of a resultant dystrophy in offspring depends on the proportion of faulty mitochondria inherited.

  
  
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  Digenic conditions are due to the combined effect of mutations in two different genes.

Classification

As well as division by inheritance pattern, dystrophies can be considered as generalized, in which the clinical effects involve the entire fundus (rod-cone or cone-rod, depending on which photoreceptor type is predominantly dysfunctional), or central (local, macular) in which only the macula is affected. They can also be classified according to the element that is the focus of the pathological process (e.g. photoreceptors, RPE or choroid), and by whether they are stationary (non-progressive) or progressive.

Introduction

The electroretinogram (ERG) measures retinal electrical activity; when stimulated by light of adequate intensity, ionic flow – principally sodium and potassium – is induced in or out of cells such that a potential is generated. 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 predominantly biphasic ( Fig. 15.2 ):

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

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

  
  
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  The c-wave is a third (negative) deflection generated by the RPE and photoreceptors.

  
  
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  Latency is the interval to the commencement of the a-wave after the stimulus is applied.

  
  
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  Implicit time is the interval from the stimulus to the b-wave peak.

Principles of electroretinography

Components and origins of the electroretinogram

Full-field ERG

A standard full-field ERG consists of five recordings ( Fig. 15.3 ) taken during diffuse stimulation of the entire retinal area, and is used to assess generalized retinal disorders but may not detect localized pathology. 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.

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  Scotopic ERG

  
  
  
  
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    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.

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

    
    
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    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.

  
  
  
  
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  Photopic ERG

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

    
    
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    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’).

  
  

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 employed 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 that affects retinal function.

Multifocal electroretinogram

Focal ERG

Focal (foveal) ERG is used to assess macular disease.

Pattern ERG

A similar stimulus to that used in visual evoked potentials (see Ch. 19 ), pattern reversal, is used to target ganglion cell function, typically in order to detect subtle optic neuropathy.

Introduction

Dyschromatopsia may develop in dystrophies prior to the impairment of other visual parameters; assessment of colour vision is also useful in the evaluation of optic nerve disease and in determining the presence of a congenitally anomalous colour defect. Colour vision depends on three populations of retinal cones, each with a specific peak sensitivity; blue (tritan) at 414–424 nm, green (deuteran) at 522–539 nm and red (protan) at 549–570 nm. Normal colour perception requires all these primary colours to match those within the spectrum. Any given cone pigment may be deficient (e.g. protanomaly – red weakness) or entirely absent (e.g. protanopia – red blindness). Trichromats possess all three types of cones (although not necessarily functioning perfectly), while absence of one or two types of cones renders an individual a dichromat or monochromat, respectively. Most individuals with congenital colour defects are anomalous trichromats and use abnormal proportions of the three primary colours to match those in the light spectrum. Those with red–green deficiency caused by abnormality of red-sensitive cones are protanomalous, those with abnormality of green-sensitive cones are deuteranomalous and those with blue–green deficiency caused by abnormality of blue-sensitive cones are tritanomalous. Acquired macular disease tends to produce blue–yellow defects, and optic nerve lesions red–green defects.

Colour vision tests

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  The Ishihara test is designed to screen for congenital protan and deuteran defects, but is simple to use and widely available and so in practice is frequently used to screen for colour vision deficit of any type. It consists of a test plate followed by 16 plates, each with a matrix of dots arranged to show a central shape or number that 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.

  
  

  
  

  
  

  

  
  

  
  

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

  
  

  (Courtesy of T Waggoner – fig. B)

  
  
  
  
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  The Hardy–Rand–Rittler test is similar to the Ishihara, but can detect all three congenital colour defects ( Fig. 15.7B ).

  
  
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  The City University test consists of 10 plates, each containing a central colour and four peripheral colours ( Fig. 15.7C ) from which the subject is asked to choose the closest match.

  
  
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  The Farnsworth–Munsell 100-hue test is a sensitive but longer test for both congenital and acquired colour defects. Despite the name, it consists of 85 caps of different hues in four racks ( Fig. 15.7D ); the subject is asked to rearrange randomized caps in order of colour progression, and the findings are recorded on a circular chart. Each of the three forms of dichromatism is characterized by failure in a specific meridian of the chart ( Fig. 15.8 ).

  
  

  
  

  
  

  

  
  

  
  

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

  
  

Introduction

Retinitis pigmentosa (RP), or pigmentary retinal dystrophy, denotes a clinically and genetically diverse group of inherited diffuse retinal degenerative diseases initially predominantly affecting the rod photoreceptors, with later degeneration of cones (rod-cone dystrophy). It is the most common hereditary fundus dystrophy, with a prevalence of approximately 1 : 5000. 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 a sporadic (simplex) disorder, or be inherited in an AD, AR or XLR pattern. Many cases are due to allelic variation (mutation) of the rhodopsin gene. XLR is the least common but most severe form, and may result in complete blindness by the third or fourth decades, generally due to loss of function of a specific protein. AR disease can also be severe, and like XLR is commonly due to loss of function in a particular pathway. Sporadic cases may have a more favourable prognosis, with retention of central vision until the sixth decade or later. AD disease generally has the best prognosis. In 20–30% of cases, RP, often atypical (see below), is associated with a systemic disorder (syndromic RP); these conditions are usually of AR or mitochondrial inheritance. A similar clinical picture can be given by drug toxicity (see Ch. 20 ). Around 5% of RP belongs to the very early-onset severe type grouped together as Leber congenital amaurosis (see separate topic).

Diagnosis

The classic triad of findings comprises bone-spicule retinal pigmentation, arteriolar attenuation and ‘waxy’ disc pallor.

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  Symptoms. Nyctalopia and dark adaptation difficulties are frequently presenting symptoms, but peripheral visual problems may be noticed; reduced central vision tends to be a later feature but can be involved earlier, including by complications such as cataract. Photopsia (flashing lights) is not uncommon. There may be a family history of RP, and a pedigree should be prepared.

  
  
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  Signs

  
  
  
  
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    Visual acuity (VA) may be normal; contrast sensitivity is affected at an earlier stage than VA.

    
    
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    Bilateral mid-peripheral intraretinal perivascular ‘bone-spicule’ pigmentary changes and RPE atrophy associated with arteriolar narrowing ( Figs 15.9A and B ).

    
    

    
    

    
    

    

    
    

    
    

    Progression of retinitis pigmentosa. (A) and (B) relatively early changes; (C) advanced changes – wide-field image; (D) end-stage disease

    
    

    (Courtesy of P Saine – fig. A; S Chen – figs B and C)

    
    

    
    

    

    
    

    
    

    

    
    

    
    

    

    
    
    
    
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    There is a gradual increase in density of the pigment with anterior and posterior spread, and a tessellated fundus appearance develops due to unmasking of large choroidal vessels ( Fig. 15.9C ).

    
    
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    Peripheral pigmentation may become severe, with marked arteriolar narrowing and disc pallor ( Fig. 15.9D ).

    
    
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    The macula may show atrophy, epiretinal membrane (ERM) formation and cystoid macular oedema (CMO).

    
    
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    Myopia is common.

    
    
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    Optic disc drusen occur more frequently in patients with RP.

    
    
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    Female carriers of the XLR form may have normal fundi or show a golden-metallic (‘tapetal’) reflex at the macula ( Fig. 15.10A ) and/or small peripheral patches of bone-spicule pigmentation ( Fig. 15.10B ).

    
    

    
    

    
    

    

    
    

    
    

    Findings in carriers of X-linked 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)

    
    

  
  
  
  
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  Complications include posterior subcapsular cataract (common in all forms of RP), open-angle glaucoma (3%), keratoconus (uncommon) and posterior vitreous detachment. Occasionally seen are intermediate uveitis and a Coats-like disease with lipid deposition in the peripheral retina and exudative retinal detachment.

  
  
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  Investigation . Investigation for mimicking infectious conditions (e.g. syphilis) is sometimes warranted.

  
  
  
  
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    Full-field ERG is a sensitive diagnostic test. In early disease it shows reduced scotopic rod and combined responses ( Fig. 15.11 ); photopic responses reduce with progression, and eventually the ERG becomes extinguished. Multifocal ERG may provide more specific information.

    
    

    
    

    
    

    

    
    

    
    

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

    
    
    
    
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    EOG is subnormal, with absence of the light rise.

    
    
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    DA is prolonged; it may be useful in equivocal early cases.

    
    
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    Perimetry initially demonstrates small mid-peripheral scotomata that gradually coalesce, and may deteriorate to leave a tiny island of residual central vision ( Fig. 15.12 ) that may subsequently be extinguished. Microperimetry (see Ch. 14 ), when available, is useful for central visual assessment.

    
    

    
    

    
    

    

    
    

    
    

    Left visual field constriction in advanced retinitis pigmentosa

    
    

    (Courtesy of S Chen)

    
    
    
    
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    Optical coherence tomography (OCT) will identify CMO.

    
    
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    Genetic analysis may identify the particular mutation responsible in an individual patient and facilitate genetic counseling, including the risk of transmission to offspring. It may also inform a decision on vitamin A supplementation.

  
  

Treatment

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  Regular follow-up (e.g. annual) is essential to detect treatable vision-threatening complications, provide support and maintain contact in case of therapeutic innovation.

  
  
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  No specific treatment is yet commercially available, but modalities such as gene therapy and retinal prostheses show promise for the future.

  
  
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  Cataract surgery is generally beneficial.

  
  
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  Low-vision aid provision, rehabilitation and social service access when appropriate.

  
  
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  Smoking should be avoided.

  
  
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  Sunglasses, ‘nanometer-controlled’ to block wavelengths up to about 550 nm, and with side-shielding, should be worn outdoors, and other light-protective strategies adopted. Indoor amber spectacles blocking to 511–527 nm may improve contrast sensitivity and comfort.

  
  
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  CMO in RP may respond to oral acetazolamide, and sometimes topical carbonic anhydrase inhibitors.

  
  
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  High-dose vitamin A supplementation (e.g. palmitate 15 000 units per day) probably has a marginal benefit, but caution may be advisable in light of potential adverse effects, notably the increased risk of lung cancer flagged by the Age-Related Eye Disease Study (AREDS) in smokers taking beta-carotene (see Ch. 14 ), hepatotoxicity in susceptible subjects and worsening retinal function in some genetic subtypes of RP; it should be avoided in pregnancy or planned pregnancy. If supplementation is used, visual function should be carefully monitored during the early months of treatment, and regular vitamin A blood levels and liver function testing must be performed. Lutein, possibly with zeaxanthin, may be safer alternatives and the AREDS doses may be taken. Patients with mutations in gene RHO1 may be more likely to benefit, but it should probably be avoided in patients with ABCA4 mutations (see ‘Stargardt disease’). Vitamin deficiencies should probably be addressed in all patients, though with caution, again particularly with ABCA4 mutations.

  
  
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  Several other drugs (e.g. calcium-channel blockers) have shown potential benefits but their efficacy and safety in RP have not been fully ascertained.

  
  
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  Potentially (even mildly) retinotoxic medications should be avoided or used with caution. Candidates include erectile dysfunction drugs, isotretinoin and other retinoids, phenothiazines, hydroxychloroquine, tamoxifen and vigabatrin. Potentially neurotoxic drugs (see Ch. 20 ) should also be used with caution.

Introduction

The term ‘atypical RP’ has conventionally been used to group together heterogeneous disorders clinically having features in common with typical pigmentary retinal dystrophy. The precise conditions included within this category vary between authors.

Atypical RP associated with a systemic disorder (syndromic RP)

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  Usher syndrome (AR, genetically heterogeneous) accounts for about 5% of all cases of profound deafness in children, and about half of all cases of combined deafness and blindness. There are three major types, ranging from type I (75%), which features profound congenital sensorineural deafness and severe RP with an extinguished ERG in the first decade, to type III (2%), with progressive hearing loss, vestibular dysfunction and relatively late-onset pigmentary retinopathy. Systemic features are widely variable and can include premature ageing, skeletal anomalies, mental handicap and early demise. There is often a ‘salt and pepper’ pattern of retinal pigmentation and optic atrophy.

  
  
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  Kearns–Sayre syndrome (mitochondrial inheritance) is characterized by chronic progressive external ophthalmoplegia with ptosis ( Fig. 15.13A ) associated with other systemic problems, described in Ch. 19 . The fundus usually has a salt and pepper appearance most striking at the macula; less frequent findings are typical RP or choroidal atrophy similar to choroideremia.

  
  

  
  

  
  

  

  
  

  
  

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

  
  

  
  

  

  
  

  
  

  

  
  

  
  

  

  
  
  
  
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  Bassen–Kornzweig syndrome or abetalipoproteinaemia (AR) is a condition in which fat and fat-soluble vitamin (A, D, E, K) absorption is dysfunctional. There is a failure to thrive in infancy, with the development of severe spinocerebellar ataxia. A blood film shows ‘thorny’ red cells (acanthocytosis – Fig. 15.13B ). The fundus exhibits scattered white dots followed by RP-like changes developing towards the end of the first decade; there may also be ptosis, ophthalmoplegia, strabismus and nystagmus. Vitamin supplementation and a low-fat diet are implemented.

  
  
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  Refsum disease (AR) consists of genetically and clinically distinct infantile and adult forms. Phytanic acid accumulates throughout the body, with substantial and varied skin ( Fig. 15.13C ), neurological and visceral features. Retinal changes may be similar to RP or take on a salt and pepper appearance, and there may be other ocular features such as cataract and optic atrophy. A low phytanic acid diet can retard progression.

  
  
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  Bardet–Biedl syndrome (genetically heterogeneous) can encompass a range of systemic abnormalities including polydactyly ( Fig. 15.13D ) and mental handicap. There is typically a bull’s-eye maculopathy due to cone-rod dystrophy and less frequently typical RP, RP sine pigmento and retinitis punctata albescens. Almost 80% have severe changes by the age of 20 years.

Retinitis pigmentosa sine pigmento

RP sine pigmento is characterized by an absence or paucity of pigment accumulation ( Fig. 15.14A ), which may subsequently appear with time. Functional manifestations are similar to typical RP.

Atypical retinitis pigmentosa. (A) Sine pigmento ; (B) retinitis punctata albescens; (C) sectoral

(Courtesy of Moorfields Eye Hospital – fig. B)

Retinitis punctata albescens

Retinitis punctata albescens (AR or AD) is characterized by scattered whitish-yellow spots, most numerous at the equator, usually sparing the macula, and associated with arteriolar attenuation ( Fig. 15.14B ). They are similar to the spots in fundus albipunctatus, and there is speculation and some genetic supporting evidence that the two clinical presentations are variants of the same disorder; the relative natural history of the two is yet to be completely defined. Nyctalopia and progressive field loss occur, in contrast to the benign prognosis believed to pertain in fundus albipunctatus, and the retinal findings may come to resemble those of retinitis pigmentosa.

Sector retinitis pigmentosa

Sector (sectoral) RP (AD) is characterized by involvement of inferior quadrants only ( Fig. 15.14C ). Progression is slow, and many cases are apparently stationary. Unilateral RP can also occur.

Leber congenital amaurosis

Leber congenital amaurosis (AR, genetically heterogeneous) is a severe rod-cone dystrophy that is the commonest genetically defined cause of visual impairment in children. The ERG is usually non-recordable even in early cases. Systemic associations include mental handicap, deafness, epilepsy, central nervous system and renal anomalies, skeletal malformations and endocrine dysfunction.

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  Presentation is with blindness at birth or early infancy, associated with roving eye movements or nystagmus, and photoaversion.

  
  
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  Signs are variable but may include:

  
  
  
  
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    Absent or diminished pupillary light reflexes.

    
    
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    The fundi may be normal in early life apart from mild arteriolar narrowing.

    
    
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    Initially mild peripheral pigmentary retinopathy ( Fig. 15.15A ), salt and pepper changes, and less frequently yellow flecks.

    
    

    
    

    
    

    

    
    

    
    

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

    
    

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

    
    
    
    
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    Severe macular pigmentation ( Fig. 15.15B ) or coloboma-like atrophy ( Fig. 15.15C ).

    
    
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    Pigmentary retinopathy, optic atrophy and severe arteriolar narrowing in later childhood.

    
    
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    Oculodigital syndrome: constant rubbing of the eyes may cause orbital fat atrophy with enophthalmos ( Fig. 15.15D ), and subsequent keratoconus or keratoglobus.

    
    
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    Other associations include strabismus, hypermetropia and cataract.

  
  
  
  
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  Treatment should generally be as for retinitis pigmentosa; gene therapy offers some hope for the future.

Pigmented paravenous chorioretinal atrophy

Pigmented paravenous chorioretinal atrophy (predominantly AD) is usually asymptomatic and non-progressive. The ERG is normal. Paravenous bone-spicule pigmentation ( Fig. 15.16 ) is seen, together with sharply outlined zones of chorioretinal atrophy that follow the course of the major retinal veins; changes may also encircle the optic disc. The optic disc and vascular calibre are usually normal.

Pigmented paravenous retinochoroidal atrophy

(Courtesy of C Barry)

Introduction

Cone dystrophies are in most cases actually cone-rod dystrophies, with cones being affected earlier and more severely than the rods. They are much less common than rod-cone dystrophies. Most are sporadic, with some AD and XLR inheritance. Presentation is in early adulthood, with impairment of central vision rather than the nyctalopia of rod-cone dystrophy. The prognosis is commonly poor, with an eventual visual acuity of 6/60 or worse.

Diagnosis

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  Symptoms. Gradual bilateral impairment of central and colour vision, which may be followed by photophobia.

  
  
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  Signs. The features may evolve through the stages below.

  
  
  
  
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    The macula may be virtually normal or show non-specific central pigmentary changes ( Fig. 15.17A ) or atrophy.

    
    

    
    

    
    

    

    
    

    
    

    Cone dystrophy. (A) Early pigment mottling; (B) and (C) bull’s-eye macular appearances – a choroidal naevus is also present in (C); (D) central macular atrophy

    
    

    (Courtesy of C Barry – fig. D)

    
    

    
    

    

    
    

    
    

    

    
    

    
    

    

    
    
    
    
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    A bull’s-eye maculopathy ( Figs 15.17B and C ) is classically described but is not universal; causes of a bull’s-eye appearance are given in Table 15.1 .

    
    
    
    

    Table 15.1

    
    

    Other causes of bull’s-eye macula

    
    

    
    
    
    
    
    
    
    
    
    
    

    In adults

    Chloroquine maculopathy Advanced Stargardt disease Cone and cone-rod dystrophy Fenestrated sheen macular dystrophy Benign concentric annular macular dystrophy Clofazimine retinopathy

    In children

    Bardet–Biedl syndrome Hallervorden–Spatz syndrome Leber congenital amaurosis Lipofuscinosis Autosomal dominant cerebellar ataxia

     
    
    
    
    
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    Progressive RPE atrophy at the macula ( Fig. 15.17D ) with eventual geographic atrophy.

  
  
  
  
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  Investigation

  
  
  
  
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    Fundus autofluorescence (FAF) is often the key diagnostic test, showing various annular patterns concentric with the fovea ( Figs 15.18A–C ).

    
    

    
    

    
    

    

    
    

    
    

    Investigation in cone dystrophy. (A) FAF – patient in Fig. 15.17B ; (B) patient in Fig. 15.17C ; (C) patient in Fig. 15.17D ; (D) ERG – reduced photopic responses and flicker fusion frequency; (E) wide-field fluorescein angiogram

    
    

    (Courtesy of C Barry – fig. C; S Chen – fig. E)

    
    

    
    

    

    
    

    
    

    

    
    

    
    

    

    
    

    
    

    

    
    
    
    
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    ERG: photopic responses are subnormal or non-recordable and flicker fusion frequency is reduced, but rod responses are preserved until late ( Fig. 15.18D ).

    
    
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    EOG is normal to subnormal.

    
    
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    DA: the cone segment is abnormal; the rod segment is initially normal, but may become subnormal later.

    
    
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    Colour vision: severe deuteron–tritan defect out of proportion to visual acuity.

    
    
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    Fluorescein angiography (FA) shows a round hyperfluorescent window defect with a hypofluorescent centre ( Fig. 15.18E ).

  
  

Treatment

There is no specific treatment for cone dystrophies, but lutein, zeaxanthin and omega-3 fatty acids have been prescribed in some cases. General measures (e.g. minimizing phototoxicity) as for rod-cone dystrophies should be considered where applicable.

Introduction

Stargardt disease (juvenile macular dystrophy) and fundus flavimaculatus (FFM) are regarded as variants of the same disease, and together constitute the most common macular dystrophy. The condition is characterized by the accumulation of lipofuscin within the RPE. Three types are recognized: STGD1 (AR) is the most common, and is usually caused by mutation in the gene ABCA4 ; STGD3 (AD) and STGD4 (AD) are uncommon, and are related to different genes. Presentation is typically in childhood or adolescence, but sometimes later. The prognosis for the maculopathy is poor; once visual acuity drops below 6/12 it tends to worsen rapidly before stabilizing at about 6/60. Patients with flecks only in the early stages have a relatively good prognosis and may remain asymptomatic for many years until the development of macular disease.

Diagnosis

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  Symptoms. Gradual impairment of central vision that may be out of proportion to examination findings; malingering may be suspected. There may also be complaints of reduced colour vision and impairment of dark adaptation.

  
  
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  Signs

  
  
  
  
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    The macula may initially be normal or show non-specific mottling ( Fig. 15.19A ), progressing to an oval ‘snail slime’ ( Fig. 15.19B ) or ‘beaten-bronze’ appearance ( Fig. 15.19C ) and subsequently to geographic atrophy ( Fig. 15.19D ) that may tend to a bull’s-eye configuration (see Fig. 15.19C ). A small proportion develop choroidal neovascularization (CNV).

    
    

    
    

    
    

    

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