Cortical visual impairment (CVI) and retinopathy of prematurity (ROP) are examples of vision loss secondary to perinatal factors. Retinal dystrophies and albinism are examples of vision loss associated with heredity. An example of a condition of unknown etiology that has an associated hearing impairment as well as numerous other issues is CHARGE, an acronym that stands for coloboma, heart defects, atresia of the choanae, retarded growth and development, genital and urinary anomalies, and ear abnormalities.

Studies have found CVI along with ROP to be the leading causes of vision impairment in children from developed countries (5). CVI is associated with many causes, including hydrocephalus, cerebral vascular accidents, meningitis or encephalitis, hypoglycemia, seizures, neurodegenerative disorders, and trauma whether accidental or nonaccidental. The most common cause of CVI in children is perinatal hypoxic-ischemia and subsequent blood hypoperfusion of the brain (6). As a result of a loss of oxygen to the brain, various biochemical changes occur that ultimately have deleterious effects within various areas of the brain. Broadly speaking, there are two groups of infants with very different structural changes.

With affected premature infants, magnetic resonance imaging (MRI) reveals changes to the periventricular white matter. Because the corticospinal tracts also run through this area of the brain, spastic diplegia can be involved. Spastic diplegia is the most common neurologic impairment found in this population, affecting approximately 5% to 15% (7). VI is evident in as many as 70% of the premature infants with spastic diplegia (8).

The parts of the brain more commonly affected in term infants, as reported with the use of MRI, are the frontal and parieto-occipital areas. One study found that, in general, premature individuals had poorer vision at initial visit and had less improvement in vision over time compared with term individuals (5). Further, a much higher percentage was seen of premature individuals with strabismus, ocular motor apraxia or gaze palsy, and nystagmus compared with the term population with CVI.

Thus, CVI is a heterogeneous condition associated with other medical issues and, as a result, visual outcomes will not be uniform. Because of the concomitant medical issues, it is not unusual to see variability within an individual over a series of office visits (which mirrors what parents or care givers will note). Individuals with CVI commonly have vision equal to or worse than 20/60 or may be limited to light perception only (5). Eye care practitioners are hesitant to diagnosis CVI early on because it may initially be confused with the less devastating diagnosis of delayed visual maturation. With delayed visual maturation, visual behaviors are approaching normal levels over the first 6 or so months of life. CVI, on the other hand, typically does not show rapidly improving visual skills during this time frame. CVI is diagnosed when a child has poor or no visual response to visual stimuli and yet has normal pupillary reactions and an otherwise normal eye examination. The child’s eye movements are usually full, but fixation is not typically maintained. Strabismus, nystagmus, abnormal eye movements, and optic nerve atrophy have been reported to occur in patients with CVI (9). Currently, MRI, along with appropriate serial testing by the eye care provider, provides the basis for the diagnosis (10,11). Multicenter studies that follow children from birth on and include neuroimaging, electrophysiologic
testing, such as visually evoked potentials (VEP), as well as a range of visual function tests (e.g., visual acuity, visual field, contrast sensitivity, response to color and motion) are necessary to further elaborate a more precise natural history of this condition.

Behavioral findings associated with CVI can include poor visually guided behaviors, poor fixation, and delayed visual reaction to stimuli. Visual function and visual attention appear to be quite variable. A light source tends to be a high interest target when evaluating a child with CVI (12). Brightly colored, high-contrast toys are also motivational. Children with CVI also tend to respond better to targets that are kinetic rather than stationary. Many children with CVI also tend to use their peripheral vision more effectively than their central vision, appearing as if they are looking away from the target. Therefore, when an object is presented, often times a child with CVI may turn away as they reach for it (6,13).

Some children with CVI seem to show improvement in their visual status. Most children with CVI, however, willnot regain normal vision. In a retrospective study by Huo et al. (14), 170 patients withCVI were followed for an average length of 5.9 years. At the onset of the study, thepatient was assigned a descriptive level of functioning where level 1 indicated light perception and level 5 was reliable visual acuity not better than 20/50. At the conclusion of the study, 40% of the patients improved by one level of vision, 38% showed no improvement, 14% improved by two levels, 5% improved by three levels, and 1% had improved four levels of vision. 2.1% experienced a decreasein visual functioning. In this study, no correlation was found between the cause of theCVI and prognosis; however, the earlier the child’s condition was diagnosed, the greaterthe improvement of visual functioning (14).

Mechanisms behind this recovery have been hypothesized to be attributed to the neural plasticity that exists in normal infants as a function of visual maturation and to some extent this process still functions in children with CVI (5). The mechanism behind this recovery process needs to be elucidated.

Vision educators have developed a couple of approaches to stimulating the development of vision in young children; however, none have been rigorously studied. From a visual rehabilitation point of view, studies still need to be done to confirm or elaborate the most effective intervention(s) for CVI. It would be anticipated that the child would be involved in an early intervention program and would be receiving services from vision educators, among others.

Retinopathy of prematurity (ROP), which is covered in Chapter 13, is a retinal vascular condition that adversely affects the developing retina. If left untreated, it could lead to total blindness because the retina will ultimately detach from theposterior surface of the globe of the eye. Historically, it was termed retrolentalfibroplasia with the first outbreak occurring in the mid 1940s through the mid 1950s asneonatal care was in its infancy. Incubators at the time used 100% oxygen and it wasultimately determined that reducing the level of oxygen dramatically decreased theprevalence of this condition. As our ability to care for the spectrum of prematureinfants has improved, this visually threatening condition has increased. It is believed that 5% to 18% of childhood blindness in developed countries is caused by ROP inextremely low birthweight (ELBW) (< 1000 g; < 2.2 lb) infants (15). Numerousmulticenter clinical trials have been conducted to determine levels of risk and standardof care with respect to identification, follow-up, and surgical intervention.

Studies looking at the natural history of the disease show that the earliest sign of ROP appears at approximately 31 to 33 weeks postmenstruation. The disease then progresses over the next 2 to 5 weeks (16). Threshold disease, the risk of attaining an unfavorable outcome, peaks at approximately 37 weeks postmenstruation (17). In the1980s, the International Classification of Retinopathy of Prematurity was developed describing the diseases severity by stage, location by zones, extent by clock hours of retinal involvement, and the presence of plus disease (dilation and tortuosity of the retinal vasculature at the posterior pole). Plus disease is often a sign of advancing disease (18).

The staging marks the progressive advancement of the retinal disease. Stage 1 is
characterized as a demarcation line between vascularized central retina and avascularized peripheral retina. Stage 2 includes an intraretinal ridgebetween vascularized central retina and peripheral retina. Stage 3 adds a ridge with extraretinal fibrovascular proliferation. In stage 4 is, partial retinal detachment (foveal or nonfoveal) occurs, and in stage 5 is a total retinal detachment.

The area of the retina affected by ROP is divided into three zones. Zone 1 (area centered on the optic disc and extends from the disc to twice the distance between the disc and the macula) is most centrally located, and ROP develops in this zone in those eyes in which the retina is most underdeveloped. Disease in zone 1 is more severe compared with disease limited to zone 2 (a ring, concentric to zone 1, which extends to the edge of the peripheral retina) or zone 3 (the remaining crescent area of the peripheral retina) (18).

Stages 1 and 2 do not usually require treatment, because of spontaneous regression of the disease process. Some infants who have developed stages 3, 4, 5, ROP tend to require treatment. The treatment is usually performed either by laser or cryotherapy. The studies investigating surgical intervention of cryotherapy and laser therapy found both treatments to be safe and efficacious (19,20). Today, however, laser therapy is more commonly used now than cryotherapy because of various advances in both hardware and surgical protocol of infants with stage 3 ROP who require treatment. Most of the infants who require laser or cryotherapy develop threshold disease between 32 and 42 weeks post-conceptual age (PCA).

Timing is one of the most important factors in the successful treatment of ROP, because the disease can advance very quickly and delay in treatment often reduces the chances of success. Stage 4 ROP is characterized by a partial retinal detachment. Treatment modalities consist of cryotherapy or scleral buckle. Stage 5 ROP is characterized by total retinal detachment and is described as a dense white scar behind the lens with the detached retina adherent to the fibrous scar tissue. When the disease is particularly aggressive, an open-sky vitrectomy is necessary in which as much retina as possible is surgically attached with the replacement of the vitreous and removal of the lens. The visual prognosis with these patients is guarded. In some cases, a low level of functional vision will remain. These patients are at a high risk for the development of glaucoma (21). If the treatment is monocular, then protective eyewear is indicated.

Other ocular manifestations that can occur with infants with ROP include moderate to severe myopia, strabismus, cataracts, glaucoma, nystagmus, and corneal problems (22).

Further research is needed to understand the underlying mechanism in order to eradicate this condition. Clinical guidelines ensuring screening protocols that identify at-risk infants for ROP have been instituted. These guidelines recommend two dilated fundus examinations for at-risk infants weighing less than 1500 g (3.3 lb) at birth or born with less than 28 weeks’ of gestation in addition to those at-risk infants who weigh less than 1500 to 2000 g (3.3–4.4 lb) at birth (23). Follow-up evaluations and early treatment have made a tremendous difference in reducing blindness secondary to low birthweight. With the survival of extremely premature infants increasing, screening guidelines for these infants may need to be revisited (24). Long-term care and follow-up are necessary because some are still at risk for retinal detachment, vision impairment, strabismus, and high levels of myopia.

Bilateral optic nerve hypoplasia (ONH) is more commonly found than unilateral optic nerve hypoplasia. With optic nerve hypoplasia, the discs present very small with the vasculature appearing large relative to the disc. Surrounding the disc is a white circumpapillary ring of sclera also known as a double ring sign.

Acuity levels or impact on the visual field based on the size of the disc is very difficult to predict. Vision can range from relatively normal to no light perception. The effect on the visual field may be varied in presentation as well from a generalized defect in both central and peripheral fields to subtle peripheral scotoma. ONH is a stable condition in which visual function does not deteriorate with time.

Weiss and Kelly (25) found that they were able to predict ultimate acuity by developing a formula based on the size of the optic nerve,
VEP, and preferential looking acuity results (25). In some cases, especially when monocular, there is an associated amblyopia requiring treatment (26).

This anomaly is congenital and can be associated with the following ocular findings: extremely poor acuity, sluggish pupillary reactions, nystagmus, and strabismus, in particular, or visual field defect (27,28). No predilection is seen for gender, race, or socioeconomic group (29). Numerous contributory factors exist, including environmental, such as maternal diabetes; maternal alcohol abuse; maternal infection (e.g., cytomegalovirus, syphilis, rubella); maternal use of antiepileptic drugs; and young maternal age (27,30). Although most patients with ONH have no associated systemic abnormalities, ONH can be a factor in clinical syndromes such as septo-optic dysplasia, tumor within the anterior visual system, and significant brain maldevelopment (26,29).

Systemic findings can include associated brain disorders (e.g., an absence of the septum pellucidum), failure to thrive possibly secondary to endocrine issues (e.g., growth hormone deficiency, hypoglycemia, and hypothyroidism) (28).

Depending on the severity of the child’s visual impairment or developmental delay, it would be anticipated that the child would benefit from an early intervention program and would be receiving services from an orientation and mobility specialist as well as a teacher of the visually impaired to aid in visual function.

Albinism is the most common genetic condition causing VI in the United States. Melanin is a pigment found in skin, hair, and the eyes (31). Defects in approximately 12 genes have been identified as being responsible for the various types of albinism because they relate to the synthesis or stabilization of melanin, integrity of the melanosome membrane, and the development of the melanosome itself (32). Genetic testing is now the accepted method of appropriate identification of the form of albinism rather than the unreliable and inexact hair bulb test. This heterogeneous condition is typically associated with decreased vision, nystagmus, decreased contrast sensitivity, photophobia, and foveal hypoplasia, and iris transillumination is the hallmark sign of albinism. Delayed visual maturation is not uncommon. Many infants with albinism may appear to have minimal vision early on but will improve over the first year of life.

Ocular albinism is primarily an X-linked recessive disorder with prevalence among men of 1 of 50,000 (33,34). Men with sex-linked recessive albinism may have slightly lighter skin and hair color than their family members do, but will exhibit a subtle iris transillumination and foveal hypoplasia (34). Many patients exhibit nystagmus, pupillary hippus, photophobia, strabismus, moderate to high degrees of hyperopia, or astigmatism, and abnormal accommodation. Acuity can range between 20/50 and 20/200.

Oculocutaneous albinism (OCA), an autosomal recessive disorder, is caused by defective tyrosinase activity. It is found in 1 of 20,000 people (35). OCA1 is a result of absent or greatly reduced tyrosinase activity, an enzyme involved in the synthesis of melanin. OCA1, the more severe form, is characterized by a complete absence of melanin pigment of the skin, hair, and eyes, whereas OCA2 typically has a better prognosis because pigmentation may develop as the patient ages.

OCA1a is caused by the completely inactive enzyme, and most mutations result in the inability to produce melanin pigment throughout the patient’s life. Its gene is located at 11q14–21 (36). OCA1a is the classic tyrosinase-negative form of OCA. A typical individual is bornwith pinkish-colored skin, white hair, blue-gray irises, and a prominent red reflex. Also, typical are decreased visual acuity in the range of approximately 20/100 to 20/300, photophobia, transillumination, nystagmus, foveal hypoplasia, the misrouting of optic nerve fibers, strabismus and moderate to high degrees of hyperopia or astigmatism (37). With this type of albinism, pigmentation in the hair, skin, and eyes do not change as the patient ages.

OCA1b is characterized by reduced activity of the tyrosinase enzyme. Despite this, however, small levels of pigment can be produced and can accumulate over time. Clinical manifestations usually reveal white skin and hair, and blue eyes at birth. However, pigment may be acquired
with time. A patient’s hair, for example, may turn to a light or golden blonde, or the skin may acquire a tan as well as freckles. The ocular findings of transillumination and foveal hypoplasia with OCA1b still persist.

Patients with OCA2 may accumulate pigment with age because the tyrosinase gene is normal and the enzyme is present and functional. The gene responsible for OCA2 is on chromosome 15q11.2–q12 (36). Clinical manifestations of these patients may include pigmented hair as well as skin, including pigmented birthmarks. Over time, OCA2 albinos may have an increase in pigmentation in the skin, hair, and eyes. Irides can be blue or become a light brown, with time. The red reflex may decrease as pigment develops. Photophobia and nystagmus are usually less severe. Visual acuity is also impaired.

Corrective lenses, low vision aids, and the involvement of a teacher of the visually impaired, as well as potentially an orientation and mobility specialist, should be recommended. The National Organization for Albinism and Hypopigmentation (NOAH) is an excellent resource for information about albinism as well as resources for support of patients and families.

A condition that represents not only deaf-blindness, but has several of the common associated medical conditions listed above is CHARGE. It is a condition whose incidence is approximately 1 in 12,000 to 15,000 births (38). No gender or race predilection is found and the cause is unknown. In 1981, Pagon et al. (39) first described this condition based on six clinical characteristics. Most cases of CHARGE syndrome occur sporadically. Differential diagnosis from other chromosomal abnormalities including cat’s eye, trisomy 13,22, VACTERL (vertebral, anal, cardiac, tracheal, esophageal, renal, limb), and Joubert syndromes (40).

A definitive diagnosis of CHARGE association has been revised to include at least three major anomalous defects or at least two major and three minor anomalous defects (41). Individuals with CHARGE association, therefore, will have some, but not all of the anomalies described below. Coloboma, heart defects, retarded growth, and development and ear anomalies have been noted to present in about 80% of diagnosed cases (42).