Signs and Symptoms
As optic nerve head (ONH) hypoplasia is congenital in nature, it is typically diagnosed in younger patients at the time of their initial eye examination, though the condition in mild form may escape detection until adulthood. Patients present with variable symptoms, depending upon the severity and laterality of the condition. Visual acuity may range from normal to no light perception in the affected eye.1-3
Other dysfunctions of the afferent system, such as diminished color vision, red desaturation and brightness perception, may also be variably present. Nystagmus, amblyopia and strabismus (with esotropia being more prevalent) are encountered in a high percentage when patients are visually impaired.3,4 Visual field defects may also be elicited, but vary considerably. Inferior visual field loss has commonly been documented.5-9
There appears to be no gender predilection.3 ONH hypoplasia is typically bilateral, but may be asymmetric or unilateral in some cases.3,6,7,10,11 Myopic refractive error, which may be high, is very common.2 Examination reveals the optic nerve in the affected eye(s) to be smaller than expected, with the vasculature appearing very large relative to the disc.12,13 If the case is unilateral, there is a notable size difference in the affected nerve head when compared to the fellow eye. The affected optic disc is frequently encircled by a yellow-white peripapillary halo, bordered by a dark pigmented ring.2 This circumpapillary ring of scleral tissue creates what is termed “double-ring sign.” The normally bright reflex from the nerve fiber layer is characteristically diminished.
Commonly found in association with ONH hypoplasia is a history of maternal diabetes.7-9,14 Optic nerve head hypoplasia can also be found as part of fetal alcohol syndrome and a history of maternal drug or alcohol use during pregnancy.15-18 Endocrine abnormalities commonly manifest as growth hormone deficiency with small stature, and panhypopituitarism.11 There may also be concomitant renal maldevelopment and subsequent renal disease, which is termed papillorenal syndrome.19
There exists a variant of ONH hypoplasia termed superior segmental optic hypoplasia (SSOH).20-25 In this variant, optic nerve hypoplasia is sectorial rather than total and involving only the superior aspect of the optic disc with corresponding inferior visual field loss. Due to this superior hypoplasia, the condition has been referred to as the ‘topless disc syndrome’ and has been mistaken for optic atrophy and normal tension glaucoma.
ONH hypoplasia is one of the most common of the congenital optic nerve abnormalites.1,2 ONH hypoplasia is characterized by a lower number of optic nerve axons.
The exact mechanism responsible for ONH hypoplasia is not completely understood, but the condition is believed to represent a dysplasia of the retinal ganglion cell layer with an associated loss of the nerve fiber layer, secondary to some interruption in the development of the fetus.2 Consequently, underdevelopment of the optic nerve ensues with the posterior scleral foramen “filling in” with connective and scleral tissues. This all seems to result from defective closure of the embryonic fetal fissure.
Many disorders have been implicated in this disorder, including gestational diabetes, maternal infection by cytomegalovirus, syphilis and rubella, fetal alcohol syndrome and other drug use by the mother while pregnant as well as young maternal age.3
Approximately 50% of patients with ONH hypoplasia have associated systemic abnormalities.2 ONH hypoplasia may be part of a larger clinical syndrome historically known as septo-optic dysplasia, which is associated with concurrent hypopituitarism and an absence of the septum pellucidum and corpus callosum. This is marked by shortness of stature, congenital nystagmus, and a hypoplastic disc.
ONH hypoplasia and hypopituitarism historically has been termed de Morsier’s syndrome.2,3,11 However, recent evidence suggests that ONH hypoplasia, hypopituitarism and other endocrine abnormalities are independent of septum pellucidum development. Further, it appears that Georges de Morsier never described a case of ONH hypoplasia or recognized its association with hypopituitarism or missing septum pellucidum. In fact these associations should be attributed to William Hoyt.26,27 Thus, “Septo-optic dysplasia” and “de Morsier’s syndrome” are historically inaccurate and clinically misleading terms.
ONH hypoplasia is a congenital condition that does not change over time. Appropriate management begins with proper diagnosis, which may be made by appearance alone in some cases. If there are questions as to the exact nature of the disc appearance, visual field testing, scanning laser tomography, optical coherence tomography (OCT) and MRI may help confirm the diagnosis.
It has been shown that there is pronounced thinning of the retinal nerve fiber layer and disc abnormalities in ONH hypoplasia, which is easily demonstrated by scanning laser tomography and OCT.20-22,24,28 In addition, many clinicians will photograph the posterior pole of the affected eye and measure the disc-macula/disc-disc (DM/DD) ratio; this compares the horizontal diameter of the nerve head to the distance between the fovea and the center of the nerve. In the normal eye, the DM/DD measures between 2:1 and 3.2:1. Ratios greater than this are very indicative of hypoplasia.13 The presence of circumpapillary scleral crescent or “double ring sign” is highly diagnostic.
In adult patients who have impaired vision in the affected eye, management includes patient education and the prescribing of protective eyewear. If the history or examination is indicative of any associated systemic manifestations, the patient should be referred for studies, including MRI, to rule out neurodevelopmental and endocrine disease. Upon diagnosis in a child, such evaluation should be strongly considered due to the high prevalence of associated systemic abnormalities.
Patients with unilateral and bilateral optic nerve hypoplasia frequently have concomitant neurologic, endocrine and systemic abnormalities needing evaluation by pediatric specialists in neurology and endocrinology.29,30 In more profound cases in which both eyes are affected, visual rehabilitation services should be recommended to improve functional abilities.
Most visual debilitation in ONH hypoplasia stems from a congenital absence of optic nerve axons and dysplasia of the retinal ganglion cell layer. Any structural abnormality of the optic nerve that reduces visual ability and acuity in infancy can lead to developmental vision loss beyond that which can be explained solely by the hypoplasia.
It has been reported that these patients have a degree of “amblyopia” superimposed upon the visual deficits imparted by ONH hypoplasia.2 However, in this setting, “amblyopia” is not an appropriate term. Amblyopia is defined as vision loss in the absence of organic causes.
Despite the misuse of the term “amblyopia,” there may be some visual benefit to occlusion therapy and other visual system managements for improving the development of vision. These programs should be attempted as early as possible. However, in that there are anatomical limitations, the success of therapy should be assessed quickly and continuation of therapy should be based upon the clinical response. Electrophysiologic testing can give insight into visual prognosis. Visual evoked potential (VEP) and pattern electroretinogram (PERG) are useful in identifying future visual prognosis in infants with ONH hypoplasia.31
In cases with concurrent or resultant strabismus, surgery can enhance the patient’s quality of life, though visual improvement may be minimal. Patients with vision loss and strabismus secondary to ONH hypoplasia may achieve some limited visual improvement from therapy, but not as much as would be expected in patients without this underlying condition. Prolonged therapy in the absence of clinical improvement is inappropriate.
• It is essential that the clinician clearly distinguish vision loss secondary to ONH hypoplasia from pure amblyopia. Although both amblyopia and ONH hypoplasia can present with reduced acuity, strabismus and significant refractive error, the former remains a diagnosis of exclusion. In cases of ONH hypoplasia, the associated refractive and/or binocular findings are secondary findings rather than primary causes of the problem.
• If a child with ONH hypoplasia undergoing visual therapy shows no initial improvement within three months, therapy should be discontinued. Longer duration of therapy in these patients will not be met with late success.
• The ring of scleral tissue surrounding a hypoplastic disc can be misleading and difficult to identify. In some cases it can be misdiagnosed as optic atrophy in a normally sized nerve. Always look for centrally located “normal” colored disc tissue as well as subtle topographic changes that mark the delineation of disc tissue from scleral tissue.
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