Ocular Manifestations of Albinism

Updated: Dec 11, 2019
Author: Mohammed O Peracha, MD; Chief Editor: Hampton Roy, Sr, MD 



Albinism refers to a group of hereditary disorders that involve an abnormality of melanin synthesis or distribution.

The term albinism comes from the Latin word albus, which means white, and, in 1908, Garrod first scientifically described it.[1] Clinically, albinism presents as a pigmentation abnormality of the skin, the hair, and/or the eyes. Albinism can be divided into 2 broad categories, as follows: oculocutaneous albinism and ocular albinism. Oculocutaneous albinism involves both the skin and the eyes, whereas ocular albinism mainly affects the eyes with minimal to no skin involvement.

The primary morbidity of both oculocutaneous albinism and ocular albinism is eye related. Signs and symptoms include photophobia, refractive errors, monocular vision, strabismus, pendular nystagmus, iris transillumination defects, foveal hypoplasia, and abnormal decussation of the optic nerve fibers. These ocular manifestations are almost always present in both forms of albinism; however, the degree of their presentation can vary depending on the type of albinism and the racial background of the patient.

The inheritance pattern of albinism is also quite variable. Oculocutaneous albinism is mostly an autosomal recessive disorder, whereas ocular albinism is transmitted as a sex-linked or autosomal recessive disease.

Oculocutaneous albinism is divided into approximately 10 different types. Two of the more common forms are type I (tyrosinase negative)[2] and type II (tyrosinase positive) oculocutaneous albinism. Patients with type I disease have no skin or ocular pigmentation, whereas those with type II disease can develop some pigmentation as they grow older.

Another important form of oculocutaneous albinism is type IB, which was previously called yellow mutant oculocutaneous albinism. Patients with type IB are similar to those with type I but can exhibit some pigmentation of their skin, hair, and ocular structures.

Two additional rare types of oculocutaneous albinism with important systemic findings and an increased risk of mortality are Hermansky-Pudlak syndrome and Chediak-Higashi syndrome.

Ocular albinism type I is an X-linked disorder associated with the OA1 gene. Type I is the most common form of ocular albinism. Female carriers can show minor signs, whereas males with ocular albinism can show a constellation of any of the above-mentioned findings.[3]

The visual acuity in patients with albinism is variable and ranges from 20/40 to 20/400.[4, 5]


Melanin is the pigment responsible for skin, hair, and eye coloration. Albinism is caused by a disorder of melanin metabolism, and the defect can lie with either melanin synthesis or distribution. Melanin is synthesized in melanocytes from the amino acid tyrosine. This process takes place in special organelles called melanosomes. The pathophysiology of oculocutaneous albinism involves a reduction in the amount of melanin present in each of the melanosomes. The pathophysiology of ocular albinism is a reduction in the number of melanosomes, although each melanosome may be fully pigmented.

The most important enzyme in the synthesis of melanin is tyrosinase, which converts tyrosine to dopa. The gene for the enzyme tyrosinase has been localized to chromosome 11. A number of mutations have been found at this locus, which can result in an absent or defective tyrosinase enzyme. This results in type I oculocutaneous albinism, which is characterized by complete absence of skin and eye pigmentation, despite a normal number of melanosomes.

In contrast, the type II (tyrosine positive) oculocutaneous albinism defect is within the P polypeptide, which is a melanosomal tyrosine transporter. The P gene has been mapped to chromosome 15 and is more commonly linked with albinism in patients of African descent. These patients do have some pigment, but they have lighter pigmentation than expected due to their relatives and ethnicity.

Ocular albinism type I is an X-linked disorder related to defects in the OA1 gene. This gene produces pigment cell-specific, intracellular G-protein coupled receptor 143 (GPR143),[6] which appears to result in faulty transport of melanosomes and lysosomes as well as macromelanosomes. Patients with this disorder are found to have giant melanosomes in their skin melanocytes and retinal pigment epithelium.

The exact mechanism by which the absence of pigmentation leads to foveal hypoplasia and abnormal decussation of optic nerve fibers is not completely understood. It has been postulated that retinal pigment epithelial pigmentation around the macula is necessary for the normal development of the fovea. It also has been suggested that the absence of dopa, which is an antimitotic agent, can influence normal retinal development. This foveal hypoplasia is responsible for some degree of decreased visual acuity in almost all types of albinism. The abnormal decussation of optic nerve fibers is responsible for strabismus and monocular vision. Photophobia results from iris transillumination defects.



United States

The frequency of type I (tyrosinase negative) oculocutaneous albinism is approximately 1 in 17,000 to 1 in 20,000.

The frequency of type IB albinism appears to be higher among Amish people.

The frequency of type II (tyrosinase positive) oculocutaneous albinism is higher in the African American population, where it can be 1 in 10,000, as compared to 1 in 36,000 in Caucasian Americans.

The prevalence of X-linked ocular albinism is estimated to be 1 in 50,000.


The frequency of type I oculocutaneous albinism worldwide is about the same as in the United States.

The frequency of type II oculocutaneous albinism is higher in African countries, where it can range from 1 in 2000 to 1 in 5000.

Similarly, the frequency of Hermansky-Pudlak syndrome is much higher in Puerto Rico, where it is approximately 1 in 2700.


The main cause for morbidity in patients with albinism is decreased visual acuity.

In tropical regions, there can be higher mortality among these patients secondary to an increased incidence of skin cancer due to sun exposure.

Mortality also is increased in patients with Hermansky-Pudlak syndrome and Chediak-Higashi syndrome. Patients with Hermansky-Pudlak syndrome have a bleeding diathesis secondary to platelet dysfunction and also experience restrictive lung disease, inflammatory bowel disease, cardiomyopathy, and renal disease. Patients with Chediak-Higashi syndrome are susceptible to infection and also can develop lymphofollicular malignancy.


Albinism affects all racial groups. However, type II oculocutaneous albinism occurs more frequently in African American and African populations. Similarly, there is a much higher incidence of Hermansky-Pudlak syndrome among people of Puerto Rican origin.


Oculocutaneous albinism affects both sexes equally. Ocular albinism is a disease primarily of males because of its sex-linked transmission.


Most people with albinism are diagnosed during infancy or early childhood.


Visual prognosis in patients with albinism is quite variable. Usually, no improvement in visual acuity occurs in patients with type I oculocutaneous albinism. Visual acuity may improve with increased pigmentation in other forms of albinism as the patient grows older.




Patients with albinism usually present in early infancy and generally will have any of the following symptoms:

  • Skin, hair, and eye discoloration are caused by abnormalities of melanin metabolism. However, this might not be as obvious in patients with ocular albinism.

  • Photophobia

  • Decreased vision due to foveal hypoplasia, high refractive error, and/or nystagmus

  • Strabismus due to abnormal decussation of optic nerve fibers

  • Nystagmus - Earlier onset of nystagmus correlates with degree of foveal hypoplasia.

  • History of easy bruising or recurrent infections in patients with Hermansky-Pudlak syndrome and Chediak-Higashi syndrome, respectively

  • Decreased hearing associated with some forms of X-linked ocular albinism


All children with nystagmus should be evaluated for foveal hypoplasia and transillumination defects. Patients with subtle external pigment changes may be misdiagnosed with congenital motor nystagmus if these signs are missed.

Most patients with albinism generally have a combination of the physical findings discussed below.

Most patients with oculocutaneous albinism have obvious hair and skin discoloration. The range of skin and hair colors can vary depending on the type of albinism. Patients with ocular albinism usually have almost normal skin and hair color, but they tend to have lighter skin and hair color than their siblings, especially in darker skin populations.

The color of the iris usually is blue but can vary from blue to brown. Almost all patients have iris transillumination defects, which can be seen with direct or retroillumination at the slit lamp.

Visual acuity usually is decreased and can range from 20/40 to 20/400. Refractive errors are common and can be either myopic or hyperopic.

Patients usually have monocular vision and poor stereopsis secondary to abnormalities of the optic pathways. Patients have an increased amount of crossed nerve fibers in the optic chiasm. Patients have abnormal retinogeniculostriate projection; many of the temporal hemiretinal nerve fibers decussate rather than project to the ipsilateral geniculate body. Strabismus generally is seen and is mostly esotropic in nature. A pendular type of nystagmus is present.

Foveal hypoplasia with an absent foveal reflex is almost universal,[7] and the ophthalmoscopic signs of macular and foveal hypoplasia include the following:

  • Absence of foveal reflex

  • Absence of yellow macula lutea pigment

  • Absence of normal hyperpigmentation of foveal pigment epithelium

  • Failure of retinal vasculature to wreathe the fovea

The fundus, in general, is hypopigmented. Female carriers of X-linked albinism can have macular pigmentary mottling as well as abnormal pigmentation of the peripheral fundus.

McCafferty et al noted that, while foveal hypoplasia is the hallmark of albinism, its morphology and development can be quite variable.[8]


Albinism is a hereditary condition. No apparent conditions seem to predispose a person to develop albinism.



Diagnostic Considerations

Oculocutaneous albinism and ocular albinism should be distinguished from other disease entities that can present with cutaneous and ocular hypopigmentation, to include the following:

  • Aland Island eye disease (Forsius-Eriksson syndrome)

  • Cross-McKusick-Breen syndrome

  • Waardenburg syndrome

  • Prader-Willi syndrome

  • Angelman syndrome

  • Vitiligo

  • Congenital nystagmus

  • Achromatopsia

  • Piebaldism

  • Kallmann syndrome

  • Chondrodysplasia punctata

  • Vici syndrome[9]

Foveal hypoplasia can be present in aniridia and retinopathy of prematurity.

Iris transillumination defects can be present in pseudoexfoliation syndrome, pigment dispersion syndrome, and uveitis.

Differential Diagnoses



Laboratory Studies

Oculocutaneous albinism and ocular albinism are primarily clinical diagnoses.

The tyrosinase hair bulb incubation test is a simple test that can differentiate between tyrosinase-negative and tyrosinase-positive forms of albinism. Hair bulbs from a patient with albinism are incubated with tyrosine in a test tube. Hair bulbs from tyrosinase-positive patients demonstrate some degree of pigment production, while those from tyrosinase-negative patients have no pigment production. Since most of the albino phenotypes are tyrosinase positive, this test provides limited information in determining the exact type of albinism.

Simple blood clotting tests can be performed if Hermansky-Pudlak syndrome is suspected. The clotting parameters are reduced in patients with this disease because of defective platelets.

Imaging Studies

The visual-evoked potential (VEP) may be used to help confirm the diagnosis of albinism. Patients with albinism show an asymmetry of VEP between the 2 eyes secondary to misrouting of the optic pathways. This makes VEP a very accurate diagnostic test for albinism.

In a study of 13 patients, Seo and colleagues used optical coherence tomography (OCT) to develop a grading system based on foveal hyporeflectivity, the degree of choroidal transillumination, the presence of a tram-tract sign, and foveal depression.[10] They found that these measurements correlated with the visual prognosis.[10]

Macular OCT can be helpful in making a diagnosis of atypical cases of oculocutaneous albinism as reported by Rossi et al.[11] According to authors, OCT showed high reflectivity across the fovea without foveal depression in an atypical case of oculocutaneous albinism and helped in making the correct diagnosis. These OCT findings are a typical pattern for oculocutaneous albinism.[12]

In a study by Sepúlveda-Vázquez et al, spectral-domain optical coherence tomography (SD-OCT) showed development of inner retinal layers in the fovea, abnormality of the Henle layer, and lack of thickening in the perifoveal area.[13]

Anterior segment OCT can also be used to detect iris abnormalities associated with albinism and can help in making the diagnosis and evaluating the intensity of albinism, as reported by Sheth et al.[14]

A concentric macular ring sign can be seen via infrared reflectance, as reported by Cornish et al.[15]

Prins et al noted that MRI can help in determining the structural changes in brain and visual pathways and can also help as a diagnostic tool and in development of future treatment modalities.[16]

Mohammad et al reported on the morphologic abnormalities of the optic nerve head in patients with albinism using scleral domain OCT. They found that patients with albinism have significantly smaller cup-to-disc ratios and that their peripapillary retinal nerve fiber layer was significantly thinner than that in the control group.[17]

Other Tests

Light microscopy of the blood smear can be performed in patients suspected of having Chediak-Higashi syndrome. The blood smear from these patients shows neutrophils with large inclusions.

Even though not routinely performed, electron microscopic study of the skin or the hair bulbs is probably the best diagnostic method for albinism.

Even though still not widely available, gene sequence analysis can be performed to differentiate between various forms of albinism.


A skin biopsy can be performed to make the diagnosis of albinism in cases that are not clinically obvious. Skin biopsy also is helpful to determine the female carrier state in cases of X-linked ocular albinism.

Histologic Findings

Histologic evaluation of the skin, hair, and eyes from patients with oculocutaneous albinism reveals a generalized absence of melanin pigment. There is also an absence of foveal differentiation and generalized deficiency of retinal pigment. Lipidlike deposits can be present in ciliary and iris epithelia. In addition, abnormal melanin macroglobules are present in melanocytes. These macroglobules are present not only in the iris, ciliary epithelium, and retinal pigment epithelium but also in dermal melanocytes. These macroglobules are also present in the skin biopsy of carrier females of X-linked ocular albinism. (It should be emphasized here that, even though the subdivision of albinism into oculocutaneous and ocular forms is helpful to the clinician, it is not entirely accurate histopathologically. All forms of ocular albinism involve, to a small degree, cutaneous pigment abnormalities.) Patients with Hermansky-Pudlak syndrome have a ceroidlike material present in their tissues.



Medical Care

No specific medical treatment is available. Refractive errors should be corrected, and some patients benefit from bifocal lenses. If visual acuity is severely impaired, these patients can be helped with telescopic and other low-vision devices.

Schulze Schwering et al reported improvement of visual acuity with proper refraction in patients with oculocutaneous albinism in Malawi. They found the most improvement in patients with mild to moderate myopia, while the patients with greater than +1.5 D hyperopia did not improve much.[18]

Surgical Care

Surgical management in patients with ocular involvement is limited to ocular muscle surgery.

Strabismus surgery for esotropia or exotropia can be considered for better ocular alignment.

Large 4 muscle horizontal rectus recessions have been reported to improve visual acuity in some patients with nystagmus.

If coexistent retinal disease is present and laser photocoagulation is required (eg, for patients with diabetic retinopathy or retinal tears), laser treatment may be ineffective. Laser photocoagulation requires pigment in the retinal pigment epithelial cells for adequate absorption of laser energy.[19] If the pigment is insufficient for adequate absorption of energy, cryopexy may be used as an alternative to treat peripheral retinal lesions. For posterior retinal pathology, the cryopexy probe is not accessible and no alternative treatment is available.

Sinha et al reported on the surgical challenges and outcomes of retinal detachment repair in 10 patients with albinism. Four of their patients underwent scleral buckling procedure, and six underwent pars plana vitrectomy with silicone oil. They found that patients in both groups did well, and only two patients in the vitrectomy group developed recurrent retinal detachment after three months. They also noted that identifying the retinal breaks, creating a posterior vitreous detachment, and applying endolaser were challenging in these patients.[20]

Farahi et al reported good outcomes of cataract surgery combined with aniridia ring in patients with oculocutaneous albinism. They found that these patients had not only improved visual acuity but also significant reduction in glare and photophobia after surgery.[21]


Depending on patient presentation and historical or physical findings, appropriate consultations from various subspecialties should be obtained, as follows:

  • Hematology

    • For patients with a history of easy bruising and bleeding diathesis (to rule out Hermansky-Pudlak syndrome, which is more common in Puerto Ricans)

    • For patients with a history of recurrent infections (to rule out Chediak-Higashi syndrome)

  • Genetics - For additional genetic analysis or for genetic counseling for patients and their families

  • Dermatology - For patients with any skin lesions or any signs suggestive of skin cancer, or for dermatologic counseling (to avoid excessive sun exposure)

  • Low-vision specialist - Patients may benefit from low-vision aids to help with their daily visual activities.


Since there is an increased risk of skin cancer in these patients, they should be advised to use skin tanning lotion and proper clothing for protection against exposure to sunlight.

Long-Term Monitoring

Examine patients with oculocutaneous albinism and ocular albinism periodically to monitor their visual development and to assess the status of their refractive error and/or strabismus.


Questions & Answers