Visual Loss in Childhood and Early Teens PDF

Visual loss in childhood and the early teens is predominantly congenital or hereditary in nature.1 In this chapter the various conditions causing visual impairment in this age group are dis- cussed, with particular emphasis on the diagnostic features that are helpful in making the correct diagnos...

Visual loss in childhood and the early teens is predominantly congenital or hereditary in nature.1 In this chapter the various conditions causing visual impairment in this age group are dis- cussed, with particular emphasis on the diagnostic features that are helpful in making the correct diagnosis. The three most common clinical scenarios presenting to the ophthalmologist are discussed in detail: The neonate or young baby who appears to be visually impaired The visually impaired baby with no obvious ophthalmic abnormality The child with visual diffi culty. Recent advances in the understanding of the molecular genetics of many of these conditions have been truly exciting, and a brief review of the recent molecular discoveries is given where relevant. Visual development The refractive state of the normal neonate is 2–3 dioptres of hyper- metropia, accompanied by a high prevalence of astigmatism. At birth the globe measures 16.5 mm in diameter and over the fi rst year the diameter increases rapidly to reach an almost adult diameter of 24.5 mm.2 The spherical equivalent refractive error of full-term newborn infants is normally distributed about a mean of +2 dioptres with a standard deviation of 2 dioptres.3 The retina is well developed at term; however, the foveal region is immature, not reaching adult maturity until 4 months of age. The neural pathways are also immature at term, with cells in the lateral genic- ulate ganglion reaching adult size at age 2 years and the optic nerve becoming fully myelinated at 7 months. Coupled with increasing maturation of the visual system, the hypermetropic state reduces steadily and visual acuity improves. By the age of 20–30 months the visual acuity is estimated to be 6/6 [LogMAR 0.0]. In young children with a refractive error, the standard devia- tion of the error is greater the earlier the onset of the visual impair- ment; for example, the refractive error in tyrosinase-negative albinism would be much greater than that in Stargardt’s disease where near-normal variability is expected. Practical advice A baby who is emmetropic or myopic at birth is likely to become progressively more myopic during childhood and adolescence. Assessment of visual function Assessment of the visual acuity of a neonate or a small baby requires patience, attention to detail and a modifi cation of the techniques used for adults. The examiner should be prepared to spend a substantial amount of time on the examination. At birth the full-term neonate can see colours and faces at arm’s length, and fi xation should be present. In the term infant, fi xation is the most reliable clinical test of visual function. The type of fi xation target used, however, is of paramount importance. Practical advice Eighty-three per cent of neonates will follow a face but not a white light. A smile in response to a silent smile should be present at 6 weeks of age and indicates good central vision. Visually directed reaching, although possible at 3–4 months, is usually not a useful clinical test until approximately 6 months of age. Other important signs in a baby who is suspected of being visually impaired include the presence of abnormal ocular move- ments, abnormal pupillary reactions (although often diffi cult to illicit in the neonate), the presence of eye rubbing or poking, lack of facial mobility or expression, and the absence of optokinetic nystagmus. Visually directed reaching, although possible at 3–4 months, is usually not a useful clinical test until approximately 6 months of age. Other important signs in a baby who is suspected of being visually impaired include the presence of abnormal ocular move- ments, abnormal pupillary reactions (although often diffi cult to illicit in the neonate), the presence of eye rubbing or poking, lack of facial mobility or expression, and the absence of optokinetic nystagmus. Practical advice Abnormal eye movements and visual inattention are the most common signs of poor vision. The more uncoordinated the movements, the more impaired the visual acuity. The parents are often the fi rst to sense that there may be a visual problem with a young baby. Experienced mothers tend to present their children earlier. It is important not to dismiss parental con- cerns, as this may backfi re. A useful adage is: ‘If in doubt, believe the mother and either re-examine or refer’. Even if the eyes look normal, the parents may complain of the child not fi xing or reacting appropriately to visual stimuli. There may be an obvious abnormal- ity such as a white pupillary refl ex ‘leucocoria’ or a squint. Occa- sionally family snapshots using fl ash photography show up the absence of a red refl ex and bring this to the parent’s attention. Practical advice If in doubt, believe the mother and either re-examine or refer. On examination, the position and steadiness of the eyes in primary gaze is important. The presence of a persistent squint may indicate that there is an opacity of the media. It must be remembered that transient losses of binocular fi xation can be normal for the fi rst 3–4 months of life; after this age, most infants demonstrate con- sistent binocular ocular alignment over a range of stimulus dis- tances.4 Fusion in infants develops between 4.5 and 6 months of life. Any abnormal ocular movements such as nystagmus, or more rare abnormalities such as saccadomania or ‘dancing eyes’, may be indicative of a midline cerebral tumour. The presence of leucocoria (white refl ex) points to the diagnosis of cataract, primary hyperplastic vitreous or retinoblastoma. Enlargement of the globe may indicate congenital glaucoma. If there is no opacity of the media, detailed examination of the fundus, and in particular of the optic discs, is possible. Optokinetic nystag- mus is not a test that is specifi c for visual acuity, but one that is representative of the integrity of the visual system. It is normally absent in blind and severely brain-damaged children. In children with a profound visual problem, the parents often notice that the baby appears to be unresponsive to visual stimuli. 2.2.1 Electrophysiological testing Electrophysiological testing is extremely important in the assess- ment of poor vision in neonates and children. Experience and patience are required for the acquisition of good quality results in the very young. These tests not only help to secure specifi c diag- noses, but by systematic assessment of function along the visual pathways can also localise the problem underlying the visual defects. Among children, development as well as disease can affect electrophysiological parameters (Fig. 2.1); therefore, the diagnosis of abnormality depends critically on knowledge of the normal responses for age.5 A brief description of the most common elec- trophysiology tests and their function is given below. Visually evoked potential (VEP) detects dysfunction of the visual pathways from the optic nerve to the visual cortex Electroretinography (ERG) assesses the function of the neuro- retina. Different stimuli can be used to assess the function of the rod and cone photoreceptors separately. The ERG waveform can also be used to differentiate between dysfunction in different layers of the neuroretina and is an indicator of whether the problem lies within the macular area or the optic nerve. The P50 component is representative of macular function and the N95 component of optic nerve function, although an abnormality in one may infl uence the other Electro-oculography (EOG) assesses the integrity of the retinal pigment epithelial (RPE) cells The interpretation of electrophysiological data is a complex issue and must always be made with reference to the clinical fi ndings. Examples of expected electrophysiology abnormalities in inherited disorders are given below (see Table 2.2, p. 39) Figure 2.1 A, Normal waveforms for standard electrophysiology tests (a–f). The ERG represents the combined electrical activity within the retina. The ‘a’ wave represents the activity of the photoreceptors; the ‘b’ wave has its origin in the Muller (glial) cells. (a) The pattern ERG demonstrates good macular function (P50) peak and normal optic nerve function (N95) trough. Normal cone function is shown by a normal cone ERG (using a bright red fl ash) (b) and a normal 30 Hz fl icker ERG (c). Normal rod function is illustrated by a normal rod ERG tested under conditions that preferentially stimulate rod function (dim blue fl ash) (d). The maximal ERG response gives an indication of total photoreceptor function (e). The EOG waveform, which refl ects retinal pigment epithelial function, indicates a normal ‘dark to light’ rise which refl ects the comparison of amplitudes under dark and light adapted states (f). Figure 2.1 B, Electrodiagnostic tests from a patient with retinitis pigmentosa showing ‘fl at’ tracings for the maximal ERG (e), cone ERG (b) and rod ERG (d), indicating profound loss of photoreceptor function. There is also absence of the ‘light rise’ on the EOG (f). Interestingly, the patient’s central vision remains 6/9 [Log MAR 0.2] in either eye, indicating some preservation of central photoreceptors. This is confi rmed by the pattern ERG (a), which shows an abnormal but relatively preserved waveform. Clinical scenarios 2.3.1 The neonate or young baby who appears to be visually impaired When a baby with a suspected visual problem is presented to the ophthalmologist, important clinical signs to look for are those detailed in Section 2.2. If there appears to be a visual problem, the working differential diagnosis is as follows (this list is given in alphabetical order and is not all inclusive, as many other rare conditions exist): Albinism Cerebral blindness Congenital cataract Congenital glaucoma Congenital idiopathic nystagmus High refractive error Leber’s congenital amaurosis Macular colobomata Optic atrophy or hypoplasia Primary hyperplastic vitreous Retinoblastoma  Retinopathy of prematurity. Retinopathy of prematurity (ROP) is unlikely in a full-term infant, but if the baby was of low birthweight or pre-term (born earlier than 37 weeks) ROP should be considered. Babies with a birthweight of less than 1500 g are at risk of ROP and should be screened rou- tinely. Total visual loss from ROP has been reported in 2–4% of babies who weigh less than 940 g.6 Examination of the optic discs may reveal the diagnostic double halo of hypoplastic discs or the normal-sized but pale discs of optic atrophy. If an intracranial tumour is present, papilloedema may be seen. The heredofamilial optic atrophies are characterised by their patterns of inheritance, and hereditary optic atrophy can present in several different ways. The clinical fi ndings and age of onset are different in each group. A simplifi ed list of the spectrum of the inherited optic atrophies is shown in Table 2.1. The presence of leucocoria is often reported by the parents and, although the most common cause of leucocoria is cataract, retino- blastoma must always be excluded promptly. Retinoblastoma is a rare life-threatening tumour with complex genetic inheritance. Ch002-H1815.indd 33 9/15/2006 12:06:55 PM Ophthalmology for low vision 34 Those affected demonstrate a predisposition to retinoblastoma, which can be either heritable or non-heritable. Childhood cataract, although surgically treatable, causes signifi cant visual morbidity because of associated amblyopia, even with early surgical treat- ment. Cataracts that are present at birth or become apparent in the fi rst year of life account for just under 20% of all causes of blind registration in children under the age of 15 years in England and Wales. Genetically determined cataracts are a hetero- geneous group of disorders.7 Approximately 25% of congenital cataract is inherited in an autosomal dominant manner; autosomal recessive cataract is uncommon in Britain and is more prevalent in communities where consanguinity is common. X-linked cata- racts are rare. They usually occur in isolation, although congenital cataract can be associated with other ophthalmic manifestations such as microphthalmos, glaucoma and coloboma. Congenital cataract can also be part of a systemic syndrome, of which there are many. Congenital glaucoma occurs in 1 in 10 000 births in Western countries. Although several modes of inheritance have been documented, in most families the disorder is transmitted in an autosomal dominant manner with full penetrance. A full account of the molecular genetic details can be found at the Online Mendelian Inheritance in Man (OMIM) website (http://www.ncbi.nlm.nih.gov/omim).8 Even though the ocular globe is often enlarged at birth in congenital glaucoma owing to raised intraocular pressure in utero, an early diagnosis is advanta- geous in limiting fi eld loss and preventing increasing buphthal- mos. Evidence also exists indicating that, owing to the plasticity of the visual system, young babies may have some potential for optic nerve recovery if treated early. In the absence of a positive family history, the diagnosis can sometimes be overlooked in the early stages. Congenital glaucoma often presents with a ‘watery eye’. The crucial question on history taking is to determine whether the ‘epiphora’ was present at birth or developed later. Epiphora from nasolacrimal duct obstruction is usually not present at birth but begins when tear production becomes well established. A watery eye at birth should fl ag up the diagnosis of congenital glaucoma. Congenital idiopathic nystagmus and macular colobomata are rare causes of poor central vision, whereas primary hyperplastic vitreous presents as an opacity in the media. High refractive errors should always be kept in mind in these cases. Table 2.1 Clinical Features of the Inherited Optic Atrophies Juvenile Congenital Behr’s Optic atrophy Leber’s optic (infantile) (simple) syndrome with diabetes neuropathy ± deafness Pattern of Dominant Recessive Recessive Recessive Mitochondrial inheritance inheritance Age of onset 4–8 3–4 1–9 6–14 11–30 (years) Visual loss Mild/moderate Severe Moderate Severe Moderate to severe, depending on the mutation (see section 2.5.1) Final visual 6/12 [LogMAR 0.3] 6/60 [LogMAR 1.0] 6/60 [LogMAR 1.0] 3/60 [LogMAR 1.3] 6/60 [LogMAR 1.0] acuity to 6/60 to hand motion to 1/60 to 1/60 [LogMAR 1.0] [LogMAR 1.8] [LogMAR 1.8] Colour vision Blue/yellow defect. Severe Moderately severe Severe Dense central Note: if acquired dyschromatopsia dyschromatopsia dyschromatopsia scotoma for colours red/green defect – wrong diagnosis Nystagmus Rare Usual In 50% No No Optic discs Mild temporal Marked diffuse Mild temporal Marked diffuse Disc swelling and Pallor Other cardinal clinical signs include the status of the optic discs and retinal vasculature, the presence of intraretinal pigment depo- sition, and the pattern and distribution of retinal deposits. During the clinical examination it is important not to omit colour vision testing. It is necessary to use a method that can detect yellow/blue defects, as well as the more common red/green defect. A test that is rapid and user friendly in this age group is the City University plates or the D15, which is more convenient for children. A Jumbo D15 is available for use with visually impaired children. 2.4 Ophthalmic disorders presenting in childhood The disorders that are most prevalent in this age group are: Best’s disease or vitelliform dystrophy Cone dystrophy Optic atrophy Retinitis pigmentosa Stargardt’s disease or fundus fl avimaculatus X-linked retinoschisis. The pattern of visual loss varies with each condition, and some- times even within each disorder there can be signifi cant variation in disease progression because of genetic heterogeneity, that is, different mutations in different genes that give similar fundal appearances. A good example is retinitis pigmentosa. In optic atrophy vision may reach a stable level in childhood, whereas in the retinal dystrophies visual loss is progressive and can take 20 years to reach a level of signifi cant impairment. Optic atrophy can be inherited in several different ways, each type demonstrating slightly different clinical onsets and signs, the details of which can be found in Table 2.1. Vitelliform dystrophy or Best’s disease presents with a yellow egg-yolk deposit, usually centred on the macula. The deposit can be identi- fi ed shortly after birth or may develop later. It is described as a ‘sunnyside up’ egg and measures approximately two to three disc areas in diameter. Although the lesion is present early in life, the central vision can remain good until late in the fi rst or early in the second decade, when there is progressive loss of central vision associated with disintegration of the ‘yolk’. Visual deterioration is slow but progressive to a level of around 6/60 [LogMAR 1.0]. Occasionally the lesion becomes vascularised by choroidal vessels, at which stage the vision usually drops dramatically and the prog- nosis becomes much worse. A mutation in the bestrophin gene on chromosome 11 (VMD2; OMIM no. 607854) has been shown to cause Best’s disease.8,13 Stargardt’s disease or fundus fl avimaculatus Clinically these patients demonstrate ‘fi sh-tail’ fl ecks in the fundus (Plates 1 & 2 [Fig. 2.2]). These fl ecks are characteristically located centrally in the fundus in Stargardt’s disease and more peripherally in fundus fl avimacu- latus. It is thought that these two clinical phenotypes are part of the same clinical spectrum. In Stargardt’s disease, areas of retinal thinning and atrophy may accompany the fl ecks. The patient pre- senting with a ‘fl ecked retina’ is fairly common in clinical practice, and the differential diagnosis is shown in Figure 2.3. Recently, several genetic loci have been mapped for both autosomal reces- sive and dominant Stargardt’s disease.8,14 Cone dystrophy These patients characteristically complain of reduced vision and photophobia, and on clinical examination show defects of colour vision. Fundoscopy is often of little help as the changes can be very subtle. Electrophysiological testing is invaluable in making the diagnosis. These patients may respond positively to ‘red fi lter’ lenses, which prevent rod bleaching. The disorder may be inherited in an autosomal dominant, recessive or X-linked manner. Several chromosomal locations have been linked to this heterogeneous group of diseases.15 X-linked retinoschisis is a fairly common disorder inherited by males from their mothers, who are asymptomatic carriers. Recent work has shown that the gene responsible for this disease is located on the short arm of the X chromosome in the Xp22 region.16 The con- dition occurs almost exclusively in boys. Owing to the subtlety of the clinical signs, the diagnosis can be diffi cult to make and the pathognomonic clinical sign of foveal retinoschisis is present in only 50% of cases. Clinically the foveal area appears optically empty with radial folds in the superfi cial layer. Silver–grey spots can be found throughout the retina, with lattice changes in the periphery. A high index of suspicion is required for prompt diag- nosis. Cases that are not clinically obvious will show the charac- teristic electrophysiological change of a subnormal b-wave on Retinitis pigmentosa. Although the clinical signs of retinitis pigmen- tosa will already be well established in affected children in this age group, due to the fact that central visual acuity generally remains unimpaired until late in the course of the condition, chil- dren who have retinitis pigmentosa but a negative family history are often not diagnosed until much later in life, often not until the second or third decade. Retinitis pigmentosa has been studied extensively at the molecular level17 and is a disorder with extreme genotypic and phenotypic variation. The clinical fi ndings are discussed on page 47. Usher’s syndrome accounts for 15–20% of cases of retinitis pigmen- tosa. It is associated with deafness and accounts for 50% of deaf– blindness. Usher’s syndrome is clinically heterogeneous, with several subtypes being recognised (Table 2.3).18 Table 2.3 Subtypes of Usher’s Syndrome Type Description I Profound congenital deafness with onset of retinitis pigmentosa by age 10 years. Impairment of vestibular refl exes and clinically evident ataxia are more frequently found in this group II Moderate to severe congenital deafness with onset of retinitis pigmentosa in late teens III Retinitis pigmentosa fi rst noted at puberty, with progressive hearing loss Practical advice When an adult or older child presents with Usher’s syndrome, it is possible to discriminate between type I and type II by the patient’s speech. Type I sufferers, who have profound congenital deafness, have abnormal speech. These patients may also be ataxic, displaying signs of poor coordination. Those with Usher’s syndrome type II have normal speech patterns. Usher’s syndrome is commonly misdiagnosed or diagnosed late. It is important to ask about hearing impairment in all patients with retinitis pigmentosa. 2.5 The adolescent with deterioration in vision Many adolescents with impaired vision have had the condition diagnosed in childhood and are reviewed purely to assess their requirement for visual aids and to provide them and their family with support and information, and genetic counselling if requested. Some teenagers, however, develop problems at this stage. In this age group, visual functions are assessed in the same manner as in the adult presenting with visual loss. Extra care and attention must be given to specifi c problems experienced in education, and care must be taken in the provision of realistic career advice. 2.5.1 Disorders presenting in adolescence Conditions that can start to become symptomatic in this age group include: Best’s disease or vitelliform dystrophy Cone dystrophy Leber’s optic neuropathy Retinitis pigmentosa Stargardt’s disease or fundus fl avimaculatus. Leber’s hereditary optic neuropathy (LHON) was originally described in 1871 by Theodore Leber. Clinically, the disease presents with acute visual loss, circumpapillary telangiectatic microangiopathy, tortu- osity of the retinal vessels and oedema of the retinal nerve fi bres. The disease is transmitted from mother to child, with 85% of those affected being male. Visual loss usually develops between the ages of 11–30 years, but a range of 6–62 years has been described. Recent advances in the fi eld of molecular genetics have yielded insights into the underlying aetiology of this disease. LHON is associated with several different point mutations (spelling mistakes in the genetic code) of mitochondrial DNA that appear to be pathogenic for the disease. These are known as the 3460, the 11778, the 14484 and the 15257 mutations, with the 11778 mutation accounting for more than 70% of cases. Interestingly, patients with the 14484 mutation have a substantially better outcome than those with other mutations, with a fi nal visual acuity of 6/24 [LogMAR 0.6] in 71% of cases.19 It has also been reported that, in many patients with LHON, the severity of the disease is related to tobacco smoking. Increased cyanocobalamin and cyanide blood levels in patients support this hypothesis. Retinitis pigmentosa often presents in this age group. It is a hereditary degeneration primarily involving the photoreceptors of the retina with secondary changes in the retinal pigment epithelium and the neurosensory retina. There is an associated migration of pigment from the pigment epithelium into the retina, attenuation of the retinal vessels and atrophy of the optic nerve (Fig. 2.4 A & B [Plates 3 & 4]). The symptoms are night blindness, reduced peripheral vision (‘tunnel’ vision) and ultimately decreased central vision. This condition is inherited in a dominant, recessive or X-linked fashion, and can appear at any age. Genetic counselling is essential and recent advances in the understanding of the molecular genet- ics of retinitis pigmentosa will make genetic counselling more accurate. It has now become evident that the traditional classifi ca- tion of three types of retinitis pigmentosa (autosomal dominant, recessive and X-linked) is an oversimplifi cation, as there are numerous mutations in approximately 30 different retinal genes causing a phenotypically similar disease.17 This also explains why many patients have different symptoms and disease progression. Although many patients suffer from peripheral visual loss early in the disease, some notice central scotoma and loss of colour vision fi rst. The clinical prognostic factors important in retinitis pigmentosa are the age at onset of problems and the inheritance pattern. Patients with recessive and X-linked types tend to lose function and independence earlier, whereas those with an autoso- mal dominant condition tend to maintain fairly good vision until middle age. Practical advice In the clinical setting, bilaterally swollen discs associated with a sudden reduction of vision are unlikely to represent papilloedema. Practical advice Probably the most valuable piece of information is the pattern of visual loss in members of the same family in previous generations. Retinitis pigmentosa tends to run true to form within a particular family. Figure 2.4 C (Plates 3 & 4) The corresponding ‘binocular Estermann’ fi elds show reduction of the visual fi eld to less than 50° on the horizontal and less than 20° on the vertical meridians, rendering the patient ineligible for driving. Black rectangles indicate loss of function. Although a pigmentary retinopathy is usually due to isolated reti- nitis pigmentosa with no associated systemic disease, it should be remembered that it may be part of a more generalised neurological disorder. Two rare but important systemic diseases are abetali- poproteinaemia (Bassen–Kornzweig syndrome) and Refsum’s disease. The importance of these diagnoses lies in the fact that it is possible to limit the amount of visual loss by treatment if they are recognised early. Refsum’s disease is an autosomal recessively inherited disorder, which presents with nyctalopia (night blindness), distal sen- sory loss and weakness, anosmia (loss of smell) and deafness. Ophthalmic manifestations include corneal opacifi cation, cataract, glaucoma, pigmentary retinopathy and optic atrophy. Treatment includes strict elimination of phylol from the diet (primarily leaf vegetables, butter and animal fats). Abetalipoproteinaemia (Bassen–Kornzweig syndrome) is inherited in an autosomal dominant fashion. This disease presents with nyctalo- pia, neuromuscular disability and dietary fat intolerance. A pro- gressive spinocerebellar ataxia and retinopathy occur secondary to poor absorption of vitamin E. Treatment is with large doses of oral vitamin E in addition to a low fat diet and supplements of the other fat-soluble vitamins. Other conditions Although patients with Best’s disease, Stargardt’s disease and cone dystrophy may experience mild problems in early childhood, the condition often remains undiagnosed until visual acuity begins to fall in the early teens. Symptoms are often mild and, in the event of there being no family history, the condi- tion goes unnoticed as the child may naturally compensate well by adjusting working distances, for instance by moving closer to the blackboard. 2.6 Low vision aids 2.6.1 Use of low vision aids Although the possibility of treatment for these disorders at present is virtually non-existent, the ophthalmologist and optometrist play a key role in providing the aids and services that help make these patients functional. The exception, however, is those with bilateral congenital cataracts who, if detected early and operated on soon afterwards, can achieve relatively normal levels of dis- tance acuity through contact or intraocular lenses. One of the most important decisions for the parent of a young child is whether education will be possible in the normal schooling system. The availability of low vision aids and appropriate educational support is of paramount importance. Children and young adults are more dexterous than older adults with visual impairment, and with encouragement can utilise low vision aids very successfully. It is important that the introduction of visual aids is carried out in a non-threatening manner, and in the younger child may even be introduced as a game. The earlier the age of onset and the more severe the degree of visual loss, the more educational progress is impeded. It is the authors’ experience that most children with mild to moderate visual impairment can cope in normal school, given the following provisions: Good parental understanding of the problem Teaching and advisory peripatetic support A bright and dextrous child. 2.6.2 Practicalities of usage of low vision aids by children 1 Phakic children with an acuity greater than 6/60 [LogMAR 1.0] generally prefer to utilise reduced working distances and increase accommodation to tackle short- to medium-term near vision tasks. As demands increase and accommodation lags, low visual aids have to be used more routinely. Dome magnifi ers are often the aid of choice for albinos and those with congenital nystagmus. 2 Aphakic children require higher levels of magnifi cation and benefi t from stand magnifi cation (×3 to ×12) or spectacle magnifi ers (single vision or bifocal). Low vision aids must be used in conjunction with a spectacle or contact lens distance correction. 3 Children with retinitis pigmentosa and central visual loss benefi t from closed circuit televisions (CCTVs) and, as they get older, special software that they can utilise with a personal computer thus gaining access to on-screen enlargement and speech conversion. 4 Distance low vision aids can be used by virtually all school- aged visually impaired children, although there is sometimes resistance to use these in the public domain. The children should be encouraged to enjoy the device and consider it as a leisure appliance as well as an educational device. It is important to remember that the older child or young adult who is diagnosed as having a serious visual problem may have the added psychological adjustment of adopting a modifi ed life- style and career choice. Career plans may have to be altered, the patient may come suddenly to the understanding that driving will now not be an option when he or she comes of age, and sometimes the driving licence must be surrendered having often just been acquired. This is tragic for those who are already in employment, particularly if they depend on driving for their livelihood. There is no legal requirement for the use of a pushbike. Common sense and caution should prevail, and advice to parents of children should err on the side of caution. Practical advice For patients who have good visual fi elds but do not meet the driving criteria, the suggestion of a pushbike is a practical consideration. However, great care needs to be taken by the patient. Recent advances in understanding the molecular genetics of inherited retinal dystrophies The past 3–4 years have seen exciting advances in the understand- ing of the underlying genetics of many of the inherited ocular diseases. These advances are the scientifi c foundation of potential therapies for the future. Molecular genetic research is time con- suming, expensive and often frustrating. Often, even when the genetic location of a disease is located on the human genome map, the benefi ts of this small piece of information are not obvious immediately. The best way to illustrate the potential future bene- fi ts of this type of discovery is by an example in which patients with a particular type of rare macular degeneration – Sorsby’s macular dystrophy – have already derived clinical benefi t. Sorsby’s macular dystrophy is an autosomal dominant macular degeneration developing in the third or fourth decade. Patients lose central vision from subretinal neovascularisation and atrophy of the choriocapillaris, pigment epithelium and retina. Recently, the disease-causing gene for this disorder was linked to chromo- some 22, and the causative gene identifi ed. Following identifi ca- tion of the gene, a hypothesis of the cause of progressive visual loss was postulated and, based on the known facts, an experimen- tal treatment was tried. Vitamin A at 50 000 IU per day was admin- istered orally. Within a week, the night blindness disappeared in patients at an early stage of disease. Nutritional night blindness is thus part of the pathophysiology of this genetic disease, and vitamin A supplementation can lead to a dramatic restoration of photoreceptor function. The possibility of accurate genetic testing also allows for more accurate and earlier genetic counselling. Ch002-H1815.indd 52 9/15/2006 12:07:01 PM 2 Visual impairment in the young 2 53 Interestingly, Sorsby’s macular dystrophy shares some striking clinical features with age-related macular degeneration, the most common cause of blindness in Western countries, thereby possibly providing a valuable genetic model for this disease.20 Recent advances in the understanding of the molecular basis of retinitis pigmentosa have begun to direct research into therapies for the future. An example of this comes from Berger et al,21 who published a 1-year follow-up of eight patients who underwent adult human photoreceptor transplantation as treatment for advanced retinitis pigmentosa. These authors concluded that, although allogeneic adult human photoreceptor transplantation is feasible, the process was not associated with rescue of central vision or a delay in visual loss. However, they stated that any pos- sible slowing in the rate of retinal degeneration would take many years to determine. A gene therapy trial on the natural canine model for Leber’s amaurosis has also shown that gene therapy is successful in restor- ing navigational vision for 2 years.22 Human clinical trials involv- ing gene therapy will begin in 2006/7 for Leber’s amaurosis patients living in the UK and the USA. Advances in the genetic understanding of ophthalmic diseases have been prolifi c in the past 10 years. The available information is now so abundant that a simplifi ed list of genetic loci would not be useful. Up-to-date information on advances in this fi eld can be found in review articles by Alan Bird23 and Dean Bok.24 Compre- hensive information on the inherited dystrophies can also be found on the RetNet website (http://www.sph.uth.tmc.edu/Retnet/).25 2.8 Summary Children presenting with visual impairment present a special challenge in terms of diagnosis and management. Pitfalls for the unwary include diagnoses that may manifest few clinical signs. It is always wise to heed the worries of the parents, as they may suspect a problem early on. Children, even if quite severely visu- ally compromised, can show great versatility and dexterity, and often use visual aids to their best advantage. Visual impairment in the working age person Many of the conditions causing visual loss in persons of working age are not exclusive to this age group and have therefore been described elsewhere. Visually impaired persons in this age group may, however, reach a critical stage in their disease process and therefore experience signifi cant changes in visual function with resulting changes in circumstances and/or employment. The con- ditions described in this chapter are those that cause unexpected visual compromise in the previously normally sighted adult. 3.1 Diabetic retinopathy 3.1.1 Clinical presentation Patients with diabetes mellitus may develop none, some or all of the following retinal changes throughout life: microaneurysms, dot and blot haemorrhages, venous dilatation, venous beading and loops, hard exudate formation, cotton-wool spots, vascular occlusion, vasoproliferation, vitreous haemorrhage and tractional retinal detachment. Although dilatation of the retinal veins is the earliest clinical sign of diabetic retinopathy, this can be diffi - cult to detect on ophthalmoscopy. The earliest easily detectable sign of diabetic retinopathy is the appearance of a few tiny red dots in the retina; histological studies have shown these to be microaneurysms. Practical advice The earliest clinical changes – microaneurysms – are usually found in the area of retina just temporal to the macula. This is the vascular ‘watershed’ zone. The temporal macular area represents a watershed zone, where the medial and lateral posterior ciliary arteries meet; this is an area of potential vascular weakness. In health, the retinal capillary walls contain pericyte cells, which are responsible for maintaining tone in the capillary walls. Death of the pericytes is the fi rst histological change in diabetic retinopathy and is responsible for the formation of outpouchings of the capillary walls, known as microaneurysms.1 Once the pericytes are lost, the endothelial cells also lose their tight junctions and leakage of blood and protein into the retina occurs. Microaneurysms and small punctate haemorrhages cause no symp- toms as long as the central fovea remains uninvolved. Microaneu- rysms are particularly obvious on fl uorescein angiography and are easily distinguished from punctate haemorrhages owing to differ- ing angiographic features. The retinopathy may remain stable for many years with minor background changes or, alternatively, pro- gression may occur. Macular oedema is the commonest cause of impaired visual acuity in patients with early diabetic maculopathy. Intraretinal oedema, particularly when minor in nature, does not change the retinal transparency and is diffi cult to recognise by monocular ophthalmoscopy. A stereo view is required to detect clinically signifi cant macular oedema (CSMO). In the clinical setting, use of the simple macular photostress recovery test is helpful in deciding whether CSMO is a possibility. Practical advice The superfi eld non-contact Volk lens affords the observer a wide- angled stereo view of the posterior pole and peripheral retina, and is useful in the diagnosis of diabetic retinopathy and, in particular, CSMO. The resolution of the lens can be enhanced using a contact lens adaptor. Deposits of hard yellowish-white material are frequently seen at the periphery of oedematous areas; these represent lipid and/or Ch003-H1815.indd 57 9/15/2006 12:07:58 PM Ophthalmology for low vision 58 protein that has ‘precipitated out’ from the oedematous fl uid (hard exudates). Unfortunately, these changes characteristically occur in the posterior pole near the macula and can cause loss of central vision. As the disease progresses, other features become apparent on ophthalmoscopy. Cotton-wool spots, which represent areas of focal ischaemia and further dilatation and beading of the retinal veins, indicate progression of retinopathy. The mechanism whereby this occurs is obscure, but is probably related to hypoxia and venous stasis. Studies indicate that approximately 30% of patients with diabetes progress to either proliferative retinopathy or macular oedema over a 14-year period.2 New vessels arise most frequently on the optic disc or along the course of the major retinal veins. Unfortunately, wherever the vessels grow on the surface of the retina, they become adherent to the vitreous. When the vitre- ous contracts, it cannot easily separate from the retina and the vitreous pulls on the fragile new vessels, causing rupture of their walls and vitreous haemorrhage. Subsequently tractional retinal detachment may also ensue. A fuller description of the clinical grading of diabetic retinopathy is shown in Table 3.1. Before the availability of laser photocoagulation, 50% of eyes with fully developed proliferative retinopathy progressed to marked reduc- tion of vision and often complete blindness.3 In the past, considerable controversy existed regarding the role of accurate control of diabetes in the prevention of retinopathy, as well as nephropathy and other vascular complications. The recent United Kingdom Prospective Diabetic Study has confi rmed that good control of blood sugar levels is important in the prevention of both microvascular and macrovascular complications.4 This study also highlighted the importance of attending to the other ‘bad companions’ of diabetes – hypertension, hypercholesterolae- mia and smoking. It is essential that all those involved in manag- ing patients with diabetes have a thorough understanding of its complications and that they are willing to devote considerable time to education of their patients. Practical advice Patient education is absolutely essential, as it is the patient who must understand and manage their disease from day to day and from hour to hour. In some diabetic units, a diabetic education centre and a diabetic liaison nurse are available to improve diabetic knowledge. Table 3.1 Grading of Diabetic Retinopathy Grade of Clinical signs Features on retinopathy angiography Background Venous dilatation Leakage from (can be preclinical); microaneurysms; microaneurysms; dot masking due to haemorrhages; blot haemorrhages and haemorrhages; hard exudates exudates Maculopathy Exudative Microaneurysms; hard Diffuse or focal leakage exudates – diffuse or from microaneurysms; circinate little, if any, capillary fall-out Oedematous Retinal thickening – focal or Predominantly diffuse; microaneurysms; intraretinal leakage ± dot and blot haemorrhages ischaemia Ischaemic Microaneurysms; large blot Widespread areas of and blotch haemorrhages ± capillary fall-out often retinal thickening involving the perifoveal arcade Pre-proliferative All features of background Widespread inner retinopathy plus cotton- retinal ischaemia; wool spots; widespread masking from large intraretinal haemorrhages; haemorrhages; IRMAs venous dilatation, beading and venous loops; intraretinal microvascular abnormalities (IRMAs) Proliferative New vessels on the disc or Widespread inner elsewhere; fi brous tissue; retinal ischaemia; pre-retinal and vitreous profuse early leakage haemorrhage; ‘raspberry’ from new vessels or abortive neovascular outgrowth 3.1.2 Prevalence of diabetic retinopathy The prevalence of diabetic retinopathy increases with duration of diabetes. In type 1 (juvenile) diabetes, retinopathy is virtually never present in the fi rst 5 years. However, 27% of those who have had diabetes for 5–10 years and 71% of those who have had dia- betes for 10 years or longer will have diabetic retinopathy. After 30 years the incidence rises to 90%, with 30% of these patients having proliferative diabetic retinopathy (PDR).5 Times of added risk are around puberty and during pregnancy. In adult onset diabetes, maculopathy is more common than proliferative reti- nopathy but may in some cases be associated with neovascularisa- tion. Often in patients with type 2 diabetes, maculopathy can be the presenting feature of the disease. Adult-onset diabetes can remain undiagnosed for many years, with severe damage to the retinal capillaries resulting in subsequent irreversible visual loss. Practical advice Visual acuity may appear good even in the presence of PDR or extensively treated non-proliferative retinopathy. 3.1.3 Laser photocoagulation and surgery for diabetic retinopathy Laser photocoagulation of the diabetic retina utilises an argon or krypton laser to coagulate ischaemic retina, rendering the isch- aemic retina non-viable and thereby removing the stimulus for neovascularisation. Recent randomised controlled studies have shown that laser photocoagulation is effective in preserving vision and slowing the rate of visual decline in diabetic patients with pre-retinal and papillary neovascularisation and early maculopa- thy.5–7 Advanced retinal neovascularisation and macular oedema respond less favourably to photocoagulation; thus, it is imperative to detect disease in its early stages by meticulous screening and careful observation of diabetic patients. Persistent dense vitreous haemorrhage, fi brovascular membranes and traction detachments, which threaten macular function, may be treated by vitrectomy. This technique may dramatically improve visual function by irri- gating blood from the vitreous cavity using an intraocular infu- sion and suction system, fi tted with a cutting head. Fibrovascular membranes may also be carefully dissected from the retinal surface.7 3.1.4 The management of diabetic retinopathy The management of diabetic retinopathy has been the subject of many excellent randomised controlled trials, with the result that many management questions have been answered conclusively. Some questions that are of paramount importance to both the patient and the surgeon are discussed below. Q.1 Does laser photocoagulation have any impact on the progression of retinopathy? Yes. Laser photocoagulation has been shown to reduce blindness in diabetic retinopathy by 50%. Q.2 When should laser be applied in proliferative retinopathy? The Early Treatment Diabetic Retinopathy Study (ETDRS) has shown that panretinal laser photocoagulation (PRP) (Fig. 3.1 [Plates 5 & 6]) should be applied when ‘high risk’ criteria are present. High-risk criteria are as follows and indicate the need for prompt and aggressive PRP: NVD (new vessels on the disc) covering more than one- quarter to one-third of the disc area NVD covering less than one-quarter to one-third of the disc area in the presence of pre-retinal or vitreous haemorrhage NVE (new vessels elsewhere) with pre-retinal or vitreous haemorrhage. Q.3 Is laser treatment equally helpful for all types of maculopathy? No. Unfortunately laser therapy is not helpful in all types of maculopathy. Exudative maculopathy responds best, in particular for patients who have circinate patterns of hard exudates. Oedematous maculopathy responds, at best, with stabilisation of vision in 30% of patients. No treatment has Ch003-H1815.indd 61 9/15/2006 12:07:59 PM Ophthalmology for low vision 62 been found to be of help in ischaemic maculopathy; in fact, laser photocoagulation can sometimes exacerbate the situation. The outcome for patients with mixed maculopathies depends on the degree of each of the above components. Patients are often disappointed if they are told that they are unsuitable for laser treatment, or that it would not be of benefi t. These patients usually have an ischaemic type of maculopathy. Q.4 Should laser treatment be applied in pre-proliferative retinopathy? No, although it would appear sensible to pre-empt complications. The reason that laser treatment is not automatically indicated in all patients who develop to pre- proliferative retinopathy is that only 50% will progress to full- blown PDR. In addition, PRP is not without side-effects. Q.5 Are there any side-effects to laser photocoagulation? Yes. The potential side-effects of laser treatment, whether permanent or transient, are many (Table 3.2). In practice, the most common side-effects of PRP are night blindness and loss of the peripheral fi eld. These side-effects are, however, well tolerated by patients and are often accepted as a necessary pay-off against the preservation of what can often be excellent central acuity. Patients who have had successful PRP often maintain 6/6 [LogMAR 0.0] vision 20–30 years later. What is often most annoying for patients is the photophobia associated with scatter PRP. This is thought to be due to internal scattering and refl ection of light from the laser scars. In providing low vision support for those with visual impairment resulting from diabetes, the key is versatility. As aspects of the underlying condition change (lens hydration, macular oedema, retinopathy), so do refractive status and visual function. Specta- cles must be kept up to date and a range of low vision aids, some of which are designed to enhance contrast, provided. Advice on a wide range of visual rehabilitation strategies and various forms of