Spotlight Case: Pigmentation Isn’t Just Skin Deep

  • author profile pictureAshvini K. Reddy, MD
  • author profile pictureMatthew Doerr, MD, MS

Case history

A 25-year-old Caucasian woman was referred for evaluation of chronically decreased visual acuity (VA) in both eyes. She denied any previous medical or ophthalmologic history and stated her vision had never been good, even with glasses or contact lenses. She denied any history of trauma or unusual exposures.

Best-corrected VA (BCVA) is 20/25 OU, and external examination is within normal limits. She has blonde hair and fair skin (Figure 1). Extraocular motility is normal, and the patient is orthotropic without nystagmus. 

Figure 1: Pale skin, blonde hair, and light blue irides

Slit-lamp examination is significant for pale blue irides with diffuse transillumination defects. There is no intraocular inflammation, and the lens is clear in each eye. Fundus examination is remarkable for pink optic discs and the absence of a foveal light reflex in both eyes with a “blonde” fundus (Figures 2a and 2b). OCT demonstrates an abnormal foveal contour (Figure 3).

What’s your diagnosis?

The patient has a mild variant of oculocutaneous albinism (OCA). The diagnosis is supported by the presence of:

  • Fair skin
  • Blonde hair
  • Light irides
  • Iris transillumination defects
  • Foveal hypoplasia

Figure 2a: Blonde fundus with hypopigmentation OS

Figure 2b: Blonde fundus with hypopigmentation OD


OCA refers to a group of hereditary pigmentation disorders of the eyes, skin, and hair that involve an abnormality of melanin synthesis or distribution. Albinism is divided generally into oculocutaneous albinism and ocular albinism (OA) without systemic involvement. OCA is further divided into 4 main types (OCA1 through OCA4) based on their particular genetic defect, level of tyrosinase activity, and variability in the severity of ocular and systemic pigment abnormalities. All 4 types of OCA are inherited in an autosomal recessive fashion, whereas OA is typically X-linked recessive.

Figure 3: Foveal contour absent OU

OCA1 and OCA2 are the 2 most common forms of this disorder and are distinguished mainly by the level of tyrosinase activity. In OCA1, a mutation in the TYR gene on chromosome 11 limits the formation of the enzyme tyrosinase and the normal production of melanin. This leads to a general absence of pigment, despite a normal number of melanocytes.[1]

In OCA2, the melanocortin 1 receptor (MCR1) gene on chromosome 16 is altered. MCR1 is involved in the regulation and production of melanin and plays an important role in the determination of skin and hair color in normal individuals.[1] Alterations to MCR1 in OCA2 portend the classic phenotype of albinism; however, there is variability in severity depending on the amount of tyrosinase activity and type of melanin produced. OCA2 generally tends to be less severe than OCA1.[2]

OCA3 and OCA4 are much less common and are found primarily in certain ethnic groups such as Sub-Saharan African and Asian populations, respectively.[3]

While a deficiency or complete lack of skin and hair pigmentation increases the risks of sunburn and sun damage-related skin cancers, the primary morbidity of OCA is eye related. It is generally believed that proper pigmentation of the RPE is important for differentiation and development of the fovea, although this is poorly understood.[4]

Foveal hypoplasia is present in all forms of albinism and can cause variably reduced VA and poor development of the fixation reflex early in life. It is commonly associated with a pendular nystagmus.[4] Relative lack of pigment is also responsible for diffuse transillumination defects of the iris and subsequent photophobia. Abnormal decussation of optic nerve fibers contributes to strabismus and poor binocularity and is commonly observed in various forms of OCA. The exact etiology of this observation is unclear but commonly observed on evoked visual potential testing.[1,4]

While there is no treatment for the ocular manifestations of OCA, proper patient education and precautions regarding sun protection and genetic counseling are advised. Additionally, certain rare forms of OCA can be associated with Hermansky-Pudlak syndrome or Chédiak-Higashi syndrome. Thus, a thorough history should be taken with regard to bleeding disorders or frequent infections, requiring referrals to other specialists.

Take-home points

  1. OCA is a relatively uncommon (1 in 15,000 depending on type of OCA and patient ethnicity) autosomal recessive pigment disorder of the hair, skin, and eyes.
  2. While visual acuity and ocular/systemic morbidity are variable, all patients with OCA demonstrate some degree of foveal hypoplasia and iris transillumination defects.
  3. It is important to take a thorough medical and family history for each patient suspected of having OCA, as certain serious medical conditions may be present. It is also important to provide adequate family and genetic counseling.


  1. Okulicz JF, Shah RS, Schwartz RA, Janniger CK. Oculocutaneous albinism [published online April 16, 2003]. J Eur Acad Dermatol Venereol. 2003;17(3):251-256.  doi:10.1046/j.1468-3083.2003.00767.x.
  2. Yi Z, Garrison N, Cohen-Barak O, et al. A 122.5-kilobase deletion of the P gene underlies the high prevalence of oculocutaneous albinism type 2 in the Navajo population [published online December 5, 2002]. Am J Hum Genet. 2003;72(1):62-72.
  3. Inagaki K, Suzuki T, Shimizu H, et al. Oculocutaneous albinism type 4 is one of the most common types of albinism in Japan [published online February 11, 2004]. Am J Hum Genet. 2004;74(3):466-471.
  4. Seo JH, Yu YS, Kim JH, Choung HK, Heo JW, Kim SJ. Correlation of visual acuity with foveal hypoplasia grading by optical coherence tomography in albinism [published online March 6, 2007]. Ophthalmol. 2007;114(8):1547-1551.

Financial disclosures

Dr. Reddy - None.

Dr. Doerr- None.

Dr. Hau - SEQUENOM: Speaker, Honoraria; THROMBOGENICS, INC: Other, Honoraria.

Dr. Choudhry - ALLERGAN, INC: Advisory Board, Speaker, Honoraria; BAUSCH + LOMB, INC: Advisory Board, Honoraria; BAYER HEALTHCARE: Consultant, Speaker, Honoraria; NOVARTIS: Advisory Board, Speaker, Grants, Honoraria; OPTOS PLC: Speaker, Honoraria.

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