[Downloaded free from http://www.meajo.org on Saturday, October 26, 2013, IP: 41.69.90.128] || Click here to download free Android application for this journal Review Article Albinism: Particular Attention to the Ocular Motor System Richard W. Hertle ABSTRACT Access this article online Website: The purpose of this report is to summarize an understanding of the ocular motor system in www.meajo.org patients with albinism. Other than the association of vertical eccentric gaze null positions DOI: and asymmetric, (a) periodic alternating nystagmus in a large percentage of patients, the 10.4103/0974-9233.114804 ocular motor system in human albinism does not contain unique pathology, rather has Quick Response Code: “typical” types of infantile ocular oscillations and binocular disorders. Both the ocular motor and afferent visual system are affected to varying degrees in patients with albinism, thus, combined treatment of both systems will maximize visual function. Key words: Albinism, Ocular Motor System, Visual Function INTRODUCTION categories of regional hypopigmentation involving neuroectoderm (ocular albinism [OA]), neural crest (albinoidism), or both lbinism is a genetic condition of hypopigmentation caused (oculocutaneous albinism). In OA, there is hypopigmentation Aby an abnormality in melanin pigment production. The of ocular neuroectoderm (iris and retinal pigment epithelium) absence or reduction of melanin has a severe impact on the that manifests clinically with iris transillumination, macular development of the eye and visual system, such that persons hypoplasia, chorioretinal hypopigmentation, photophobia, and with albinism display a variety of ophthalmic deficits, including nystagmus. The term albinoidism is applied to a condition in foveal hypoplasia, translucency of the iris, nystagmus, reduced which hypopigmentation is limited to tissues of neural crest visual acuity and an abnormal decussation pattern at the optic origin (skin, hair, and iris stroma). Unlike patients with OA, chiasm.1,2 The characteristic, which is thought to distinguish those with albinoidism do not manifest macular hypoplasia, albinism from other visual disorders resulting in foveal nystagmus, photophobia, or decreased vision.2,4 hypoplasia and other disorders of hypopigmentation is the abnormal routing of visual pathways from the eye to the brain.1,3 EPIDEMIOLOGY Clinically, it is this abnormality in conjunction with phenotypic evaluation and ophthalmic examination that has been used to Albinism can affect people of all ethnic backgrounds. diagnose albinism. Approximately one in 17,000 people have one of the types of albinism.3,5 Prevalence of the different forms of albinism Albinism is not a single entity; it encompasses a heterogeneous varies considerably worldwide. OCA1 has a prevalence of group of congenital hypomelanotic disorders. Using one system approximately 1 per 40,000 in most populations but is very of classification oculo-cutaneous albinism (OCA1A), being the uncommon among African-Americans.3,5 In contrast, OCA2 is most severe type, is characterized by a complete lack of melanin the most common type of albinism in African OCA patients.3,5 production throughout life, while the milder forms OCA1B, The overall prevalence of OCA2 is estimated to be 1:36,000 in OCA2, OCA3 and OCA4 show some pigment accumulation over the USA, but is about 1:10,000 among African Americans.3,5 It time. These disorders can also be classified into three general affects 1 in 3,900 of the population in some parts of the Southern The Children’s Vision Center, Akron Children’s Hospital, Akron, Northeast Ohio Medical Universities, Rootstown, Ohio, United States Corresponding Author: Dr. Richard W. Hertle, 300 Locust St., Suite 490, Akron, Ohio 44302, United States, E-mail: [email protected] 248 Middle East African Journal of Ophthalmology, Volume 20, Number 3, July - September 2013 [Downloaded free from http://www.meajo.org on Saturday, October 26, 2013, IP: 41.69.90.128] || Click here to download free Android application for this journal Hertle: Eye Movements and Albinism part of Africa.3,5 OCA3 or Rufous oculocutaneous albinism has A number of inherited diseases with nystagmus show a been reported to affect 1:8,500 individuals in Africa, whereas combination of immunological and pigmentation defects.11-20 it is very rare in Caucasians and Asiatic populations.3,5 Recently, Chediak-Higashi, Hermansky-Pudlak, Griscelli, and mutations in a fourth gene were shown to be the cause of paroxysmal autonomic instability with Dystonia syndromes are albinism, OCA4, and were reported to explain the disease in all autosomal diseases with these characteristics. The molecular approximately 5-8% of German patients with albinism but 18% links between immunodeficiencies and albinism reflect the of Japanese patients.6 fact that both melanosomes and secretory lysosomes are not secreted normally. Chediak-Higashi syndrome, a disease Clinical description characterized by repeated infections and albinism, shows the All types of OCA and OA have similar ocular findings, including presence of abnormally large lysosomes and melanosomes, various degrees of early onset nystagmus, hypopigmentation of suggesting that melanosomes are not secreted normally, and iris and retinal pigment epithelium, foveal dysplasia, ametropia, supporting a functional link with the secretory lysosomes of strabismus and reduced best-corrected visual acuity [Figure 1]. hematopoietic cells.21 Photophobia and light interference may be prominent. The abnormal crossing of chiasmatic, post-chiasmatic fibers can be Diagnostic methods demonstrated by monocular visual evoked potentials. The diagnosis of OCA is usually based on clinical findings of hypopigmentation of the skin and hair, in addition to the Because albinism is often associated with decreased vision, characteristic ocular symptoms.1,3,22-25 However, due to the nystagmus, and refractive errors, recognition visual acuity may clinical overlap between the OCA subtypes, other testing vary depending on an eccentrically induced head position, such as molecular, electrophysiological or radiological may be accuracy of glasses prescription, and experience of the visual necessary.1,3,22-25 Molecular genetic testing of tyrosinase (TYR) acuity tester. Reliance on fixation preference testing, such and OCA2 are available on a clinical basis, while at present, as Teller acuity cards, to assess vision has been required for analysis of tryparedoxin peroxidase gene (TYRP1) and Ter patients younger than 2 years.7 Sweep visual evoked potential macrodomain organizer matS-binding protein gene (MATP) is (VEP) testing is a novel technique that can be used to assess on research basis only.1,3,22-25 visual acuity in pre-verbal patients with albinism.8 Reports have demonstrated a correlation between binocular grating acuity Increased crossing of optic nerve fibers in the chiasm is one of and future letter recognition acuity in patients with ocular and the most consistent findings in albinism in all species.26,27 In oculocutaneous albinism.9 Studies demonstrates that sweep humans, it has been found to be highly specific and asymmetries VEP testing can be used as a predictive tool for recognition in visual evoked potentials are very helpful as a diagnostic acuity in patients with albinism.3,8,10 It has been reported that tool for albinism. While the great majority of children with Teller acuity over-estimates recognition acuity in children with albinism show crossed hemispheric asymmetry on visual evoked albinism. Because albinism is a rare diagnosis, most published potentials, occasional all otherwise classic albinism show no studies that compare grating with recognition acuity involve evidence of hemispheric asymmetry.26,27 small patient numbers.3,8,10 Individuals with mild ocular or oculocutaneous albinism are often misdiagnosed as having idiopathic Infantile Nystagmus Syndrome (INS). The finding of subtle signs of ocular hypopigmentation in some infantile nystagmus and anomalous head postures (AHPs) [Figure 2] syndrome patients with good vision has led to speculation that patients with idiopathic INS may actually be heterozygous for albinism. Simon et al. have demonstrated that when patients with INS are carefully examined, many show iris transillumination, blunting of the macular reflex, and chorioretinal hypopigmentation consistent with albinism.28 In evaluating the INS patient, it is critical to perform a careful slit lamp examination with the room lights turned off, the door closed, and a retro-illumination through a thin, axial light beam to detect basal iris transillumination. Varying degrees of macular hypoplasia (absence of the foveal pit, absence of macula lutea pigment, absence of normal Figure 1: Typical appearance of skin, hair, lashes and eyes of patient with oculo- macular pigment epithelial hyperpigmentation, and passage cutaneous albinism 1. Complete iris transillumination is also illustrated of retinal vessels through the fovea), together with other Middle East African Journal of Ophthalmology, Volume 20, Number 3, July - September 2013 249 [Downloaded free from http://www.meajo.org on Saturday, October 26, 2013, IP: 41.69.90.128] || Click here to download free Android application for this journal Hertle: Eye Movements and Albinism Figure 2: A composite illustration of the typical differences in the photographic Figure 3: Illustration of typical anomalous head posturing in patients with albinism. appearance of a normal optic in disc (top) and patient with albinism