Visual Function in Albinism: contribution of ocular abnormalities and pigmentation.

Albinism is a pigmentation disorder that can be restricted to the eyes (ocular
albinism) or can involve eyes, hair and skin (oculocutaneous albinism). The
ocular abnormalities in albinism comprise nystagmus, iris translucency, foveal
hypoplasia, optic nerve abnormalities and misrouting, i.e. an abnormal
projection of the visual input in the cerebral cortex. Usually the disorder
results in a non-progressive reduced visual acuity. A visual acuity of 0.7
logMAR to 1.0 logMAR is common (0.2 -0.1 Snellen). (Summers, 1996). However,
albinism shows a great variety in clinical presentation and patients with a
near normal visual acuity are known. The relative contributions of the
different ocular abnormalities to the visual disability are still unkown. To
investigate this we will compare patients with albinism on both ends of the
spectrum, with relatively poor and relatively good visual acuity.
The ocular abnormalities were considered to be secondary to the lack of
pigmentation. However, we question this hypothesis because of the recently
discovered FHONDA: Foveal Hypoplasia Optic Nerve Decussation defects and
Anterior segments dysgenesis. Patients with this disorder present with the same
ocular abnormalities as seen in albinism, but without a lack of pigmentation.
All patients with FHONDA have severely reduced visual acuity. Thus, it seems
unlikely that the ocular abnormalities in albinism are caused by the lack of
pigmentation. In order to give an accurate prognosis for young children with
albinism, it is necessary to gain more insight in the precise relationship
between ocular pigmentation and the development of the visual system. To this
end we will compare patients with albinism with patients with similar ocular
abnormalities and normal pigmentation, i.e. patients with FHONDA or Idiopathic
Infantile Nystagmus (IIN).

Recently we started a retrospective study of patients with albinism, FHONDA and
IIN. We collected clinical, genetic and electrophysiological data from the
records of patients with albinism seen at Bartiméus and the Leiden University
Medical Center (LUMC) and patients with FHONDA and IIN seen at Bartiméus. Until
now approximately 480 patients have been included. Evaluation of these data
confirm the large variety in signs and symptoms in patients with albinism.
These data will be used in this prospective observational case series as well.

1. To investigate the relative contributions of different ocular abnormalities
to the visual function.
2. To investigate the precise relationship between ocular pigmentation and the
development of the visual system abnormalities.

The study is a prospective observational case series. We will select patients
of 12 years or older from the retrospective study. Selection criteria for the
albinism group are a BCVA of more than 0.8 logMAR (less than 0.16 Snellen) or
BCVA of less than 0.3 logMAR (more than 0.5 Snellen).
We will invite these patients for a repeat clinical examination, to obtain a
complete dataset including VEP for misrouting and an eye-tracker test to
quantify nystagmus. If possible, this repeat examination will replace a regular
control visit.
We will then compare the clinical data of patients with relatively good BCVA to
those with relatively poor BCVA. We will furthermore compare patients with
albinism to patients with an overlap in symptoms, but without hypopigmentation,
i.e. patients with FHONDA or IIN. Of the latter patients, most information will
be available from patients* records. However, if data are missing or are of
insufficient quality, we will invite these patients to Bartiméus as well. All
tests will be performed during one visit. Duration of the visit will be
approximately 3 hours including VEP testing, or, 1 hour if VEP is not
necessary. All investigations will be performed in Bartiméus, because most of
the patients are known in Bartiméus and uniformity of the used equipment will
lead to better interpretation of the results.
We will invite patients to participate by written invitation in which the
procedures and research goals are explained. In case patients visit the clinic
for other purposes, we will ask these patients to participate after oral
explanation of the research and provide them with additional information in
writing. Subjects will only participate after informed consent, of the patients
themselves, or, in case of minors, also of their parents or legal guardians.

There is no risk to the health of the participants. The burden involving
participation in this investigation will be minimal: approximately three hours
at Bartiméus for ophthalmological and electrophysiological examination,
including a VEP (visual evoked potentials) test, an OCT (optical coherence
tomography), and fundoscopic imaging. These investigations are standard
clinical procedure for all new patients referred to Bartiméus with a possible
diagnosis of albinism. We will only perform electrophysiological tests, OCT and
fundoscopic images if they were not obtained earlier or are of insufficient
quality for the purpose of this study. The patients will be asked if they want
us to share the obtained data with their own ophthalmologist. This means that
the visit to Bartiméus may replace a regular control visit. No mydriatic
eyedrops will be administered, since dilatation of the pupils won*t be
necessary. Patients will be compensated for their travel expenses based on
¤0.19 per kilometre, or public transportation fare based on 2nd class train
tickets.