Conditions: Albinism Oculocutaneous Albinism
Keywords: levodopa Albinism dopamine oculocutaneous albinism vision retina function
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 20
Healthy volunteers: no

Brief summary:
The purpose of the study is to evaluate and document physiologic and functional changes in visual performance and retinal function of patients diagnosed with albinism (a dopamine deficiency state) following a trial of oral Levodopa/carbidopa treatment.

Detailed description:
In this study the investigators propose that the retina itself in albinism is deficient in dopamine, and vision improvement will occur as a result of improved retinal function in response to the deficient neurotransmitter dopamine. This study has a pretest-posttest design in order to determine if improvement in vision is in response to replacement of deficiency (dopamine). The electroretinography (ERG) testing and optical coherence tomography (OCT) will be critical determinants to confirm vision improvement as a result of improved retinal function, but are not primary outcome data. Main outcome measures will be collected at pre-treatment, 1 month, 3 months, and 4 months. Change in visual acuity as measured in logMAR by Snellen or sweep visual evoked potential (SVEP) after 3 months of treatment is the primary outcome. Patients include OCA1a patients, OCA1b, OCA2, and unclassified Oculocutaneous albinism (OCA). OCA1a patients clinically are known to have the worst vision, and physiologically have the lowest (or absent) levels of tyrosinase function (Dopamine Production). All patients will be treated with Levodopa/carbidopa 4mg/kg/day in three divided doses.

Arms:
arm 1: Treatment drug taken orally three times daily

Interventions: intervention 1: Levodopa/carbidopa
Intervention descriptions: intervention 1: This study will have an intent to treat goal. Anyone that fits the inclusion criteria for the study will be entered and receive study drug.

Protocol document:
Prot_SAP_000.pdf: 
 
1 
Title: Vision Response to Dopamine Replacement 
 
PI: 
Michael C. Struck, M.D. 
 
Associate Professor 
 
Department of Ophthalmology 
 
University of Wisconsin 
 
Version 9: September 2017 
 
Co-Investigators: 
 
David Gamm M.D. PhD 
 
Jim VerHoeve PhD 
 
Yasmin Bradfield M.D. 
 
Terri Young, M.D. 
 
Melanie Schmitt, M.D. 
 
 
 
Study Coordinator: 
 
Angie Adler 
 
 
Statistics: 
Scott Hetzel M.S. Research Assistant University of Wisconsin - 
Madison Department of Biostatistics and Medical Informatics 
4269A HSLC 750 Highland Ave. 608-265-4311 
hetzel@biostat.wisc.edu 
 
Ralph Trane 
Assistant Researcher 
Department of Ophthalmology & Visual Sciences 
School of Medicine & Public Health 
University of Wisconsin-Madison 
310 N. Midvale Blvd, Suite 205 
Madison, WI  53705 
rtrane@wisc.edu 


 
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The purpose of the study is to evaluate and document physiologic and functional 
changes in visual performance of patients diagnosed with albinism (a dopamine 
deficiency state) following a trial of oral Levodopa/carbidopa treatment.  
 
Background: 
 
One person in 17,000 in the U.S.A. has some type of albinism. Albinism 
affects people from all races. Albinism always affects vision. The degree of vision 
impairment varies with the different types of albinism. Additionally, because it is 
present at birth, albinism contributes to bilateral organic amblyopia in the affected 
individual, which will lead to additional irreversible visual handicap if not treated 
before 7 years of age.1 
 
There is presently no treatment that can replace the lack of melanin or 
treat the deficiency that causes the symptoms of albinism. We can only treat the 
eye problems that often accompany the diagnosis. Glasses or corrective lenses 
and low vision aids can improve vision but usually cannot correct vision to 20/20. 
For reading, children with albinism may need materials with large print text, 
depending on the severity of their vision problems. There is no treatment for 
involuntary eye movements (nystagmus) or the sensory deficits associated with 
albinism.  
 
Oculocutaneous albinism results from autosomal recessive inheritance. In 
tyrosinase-negative albinism --OCA1 (the most common type), melanosomes 
don't contain melanin because they lack tyrosinase1-2, the enzyme that stimulates 
melanin production. These patients also tend to have the worst visual prognosis. 
The production of melanin, at the cellular level, requires the biochemical 
conversion of tyrosine to eumelanin or pheomelanin. The first step in this 
biochemical pathway is the conversion of tyrosine to dopamine by the tyrosinase 
enzyme. 
 
Recently, work in several areas of dopamine deficient states (Parkinson 
disease, cocaine withdrawal disorder, Phenylketomuria) has shown that retinal 
tissue is one of the richest in the concentration of dopamine. Indeed, 15 different 
visual functions and 13 types of dopamine retinal pathologies have been 
attributed in some way to the retinal dopamine system3. The extent to which the 
absence of dopamine in the retina of patients with albinism affects their visual 
function is unknown.  
 
Levodopa/carbidopa replacement therapy has been used and studied in 
children with amblyopia since 19924. This therapy has been shown to be safe 
and effective in the treatment of children with amblyopia at dosages of up to 
3mg/kg/day body weight7.  Standard treatment in children with Dopa responsive 
dystonia (DRD) is 10mg/kg/day.17 Levodopa/carbidopa has also been studied as 
a treatment in children with retinal disease5 and shown to have a beneficial effect, 
however none of the patients in this report carried the diagnosis of albinism. 
The use of Levodopa/Carbidopa has been approved by the FDA for 


 
3 
treatment of Parkinson’s disease. As such, it was not specifically tested in 
patients less than 18 years of age. Subsequently, it has been shown to be a safe 
and effective treatment in multiple studies as an off-label use for the treatment of 
amblyopia in children under 10 years old without adverse effect3-8.  It also has 
been used by pediatric neurology for treatment of children with dystonia. 
Parkinson's disease typically requires increasing doses of Levodopa/carbidopa 
over many years, and eventually side effects occur. In contrast, children with 
Dopa-responsive dystonia often have complete resolution of symptoms on very 
low doses of Levodopa/carbidopa, with no need to increase the dose over time. 
Exceptions to this have been reported.16 
 
 
Study Objectives: 
 
Prior studies in children with Levodopa/carbidopa, have proposed that the 
improvement in visual acuity is related to a change in the neural network of the 
striate cortex (amblyopia treatment)3-8.  In this study we propose that the retina 
itself in albinism is deficient in dopamine, and vision improvement will occur as a 
result of improved retinal function in response to the deficient neurotransmitter 
dopamine. This study has a pretest-post-test design in order to determine if 
improvement in vision is in response to replacement of deficiency (dopamine). 
The OCT will be a critical determinant to confirm vision improvement as a result 
of improved retinal function, but are not primary outcome data.  Additionally, 
patients with albinism have been shown to have impaired color vision and 
contrast sensitivity, it is unclear if these visual functions will be affected by 
treatment, therefore data will be analyzed to determine if there is a treatment 
effect other than on visual acuity alone. 
Main outcome measures will be collected at pre-treatment, 1 month, 3 
months, and 4 months. Change in visual acuity as measured in logMAR by 
Snellen or SVEP after 3 months of treatment is the primary outcome.  
Additional outcome measures will be collected at pre-treatment and 3 
months, and will include color vision (Farnsworth 15 or 100 hue), contrast 
sensitivity, optical coherence tomography (OCT), and color photography.  
Because of the issues of possible permanent vision loss due to amblyopia 
as mentioned above, it is important that the effect be studied in children under 
age 7, in whom the irreversible effect of amblyopia has not occurred. Additionally 
however, children under 3 years of age are generally not able to subjectively 
participate in some of the testing proposed in this study, therefore the lower age 
limit will be included to provide patients who will be able to complete the testing. 
Finally, older patients with albinism may still appreciate an improvement in vision 
function from replacement therapy, despite the fact that there may be a ceiling on 
the improvement in vision because of the pre-existing amblyopia. Older children 
and adults will be included to allow for optimum assessment of vision recovery at 
all ages and for ability to satisfactorily recruit the number of patients necessary. 
Further studies will need to be designed to study the effects in younger children, 
and to isolate the vision effect (if found) based on the amblyopia factor.  
In use in children this medication is available in liquid form and will be 


 
4 
prepared and dispensed by the UW/AFCH for subjects who are unable to 
swallow pills or take solid medications. 
 
Patients will undergo a 3-month treatment period followed by a 1-month 
follow-up period. Visit length and testing is typical for an initial 
evaluation/consultation in the pediatric ophthalmology clinic. All testing is 
performed in the pediatric ophthalmology clinics by staff experienced and trained 
in visual testing of the pediatric population. The PI has 15 years of clinical 
experience in pediatric ophthalmology alone and is fellowship trained in pediatric 
ophthalmology, it is well within the ability of most all patients to perform these test 
within one setting except where noted based on age. In some cases it is 
expected that tests other than the primary outcome data may not be obtainable in 
all patients.  Patients will be removed from the study if they cannot complete the 
primary outcome (visual acuity) testing. Other vision testing (color testing, SVEP, 
Contrast, photography, and OCT) will be requested, but not required to 
participate in the study. Please see schedule of visits below for detail. 
 
Research Design: 
 
Patients with Oculocutaneous albinism will be recruited ages 3 and up, 
weight greater than 25 pounds. Entrance into the study is dependent upon 
clinical evidence of decreased or absent pigmentation in skin, hair, and eyes. No 
ocular only albinos will be recruited.  Additionally, all patients enrolled in the 
study will be requested but not required to undergo genotyping (TYR and OCA2 
gene) of their form of albinism, if not already known. These two types of albinism 
are the most common, and, for most clinical observers – indistinguishable. 
However, the presence or absence of TYR theoretically has a direct impact on 
expected visual response to dopamine replacement. The genotypic form of 
albinism has no known implications for other aspects of health, clinical care, 
overall health prognosis or insurability. Indeed, because the genotype has no 
influence on diagnosis or treatment, it is expected that less than one in ten 
patients recruited will have been previously tested. Testing will be performed by a 
certified national clinical lab with validated testing. No “out of pocket” expense for 
this test will be incurred by the family of the patient. Costs for testing will be 
covered by funding from the UW Department of Ophthalmology.  
 
Exclusion criteria include children under 3 or less than 25 pounds, or 
ocular pathology not attributable to albinism. Additionally, patients taking 
nonselective monoamine oxidase (MAO) inhibitors, a self-reported history of 
depression, neurologic disease, a history of myocardial infarction, peptic ulcer or 
who are pregnant or nursing will be excluded. All females that are old enough to 
have had a menstrual cycle will require a negative urine pregnancy test. For 
minor females that are old enough to have had a menstrual cycle, the subject will 
be informed of the requirement for pregnancy testing, given an opportunity to 
discuss the study requirements with the study team privately, and given the 
opportunity to decline participating in the study without giving a reason. 
 
None of the standard treatments, spectacles, surgery, and occlusion 


 
5 
therapy or vision aides will be withheld during this study.  
 
Subject identification and recruitment 
Initial contact about the study will be made via letter or in-person by the PI 
and/or Co-Investigator during a routine clinic visit.  Physicians not directly 
involved in the study can refer patients to the PI and/or Co-Investigator for 
potential inclusion into the study.  Additionally, potential subjects or guardians of 
subjects can reach out to the PI or study coordinator if they become aware of the 
trial through one of the recruitment sources (documents or clinicaltrials.gov). 
 
Potential subjects (those with a diagnosis of albinism in the UWHC medical 
record database) were mailed a letter signed by the Principal Investigator inviting 
them to join the study.  These letters were addressed to the subjects if they were 
of consenting age or to the parents/guardians if the subject was a minor.  The 
letter asked the subject (if adult) or the guardian (if a minor) to respond to the 
invitation.  That person was asked to call the study coordinator and complete a 
telephone screening questionnaire, if interested.  If the subject was found to be 
eligible for the study and was willing, a screening visit was scheduled.  At the 
screening visit, the full consent form and assent form (if applicable) was 
discussed before any study procedures were initiated.  If there was not a 
response from the potential subject or guardian within 30 days, the study 
coordinator tried to contact the potential subject or guardian.  Two attempts were 
made to contact the subject or guardian. This recruitment method has been 
completed. 
 
 
Other recruitment methods that were approved for #2012-0023 but will not 
be used under this replacement protocol: 
• Recruitment documents for placement in the monthly School of Medicine 
& Public Health Brief email, in National Organization for Albinism and 
Hypopigmentation newsletters, and possible publication by the 
Associated Press.   
• A video about study was recorded by Dr. Struck for use on the 
Department of Ophthalmology & Visual Sciences website here at the 
University of Wisconsin-Madison.   
 
 
Recruitment methods for the replacement study include listing this study 
on the clinicaltrials.gov website.  Potential subjects can search this website 
anytime for possible studies related to their condition. Potential subjects or 
parent/guardians of potential subjects can contact the study team to inquire 
about the study.  Initial contact has to be made from the potential subject or 
subject’s parent or guardian.  If oral consent is given, the telephone screening 
questionnaire will be completed. If the subject is found to be eligible for the study 
and is willing, a screening visit will be scheduled.  At the screening visit, the full 
consent form and assent form (if applicable) will be discussed before any study 
procedures are initiated. 
 
 


 
6 
 
Currently, this study is also listed on the Department of Ophthalmology 
and Visual Sciences website.  A brief description of the study along with the 
inclusion/exclusion criteria are listed.  The PI and study coordinator are listed 
along with the telephone number of the coordinator.  The general public could 
look at this website and see this clinical trial listing and reach out to us as well. 
Initial contact has to be made from the potential subject or subject’s parent or 
guardian.  If oral consent is given, the telephone screening questionnaire will be 
completed. If the subject is found to be eligible for the study and is willing, a 
screening visit will be scheduled.  At the screening visit, the full consent form and 
assent form (if applicable) will be discussed before any study procedures are 
initiated. 
 
Information collected from the record will include patient’s age, sex, race, 
genotype of albinism (if known) and the outcome measures listed above, results 
of clinical testing will be recorded in the clinic chart in addition to a study chart 
and research will only be recorded in the study chart. Research tests including 
results of genotyping will not be shared with subjects or family. For females who 
have had a menstrual cycle, positive results of screening pregnancy tests will be 
given to the subject in private, not shared with the parent. 
  
 
Patients include OCA1a patients, OCA1b, OCA2, and unclassified OCA. 
OCA1a patients clinically are known to have the worst vision, and physiologically 
have the lowest (or absent) levels of tyrosinase function (Dopamine Production). 
All patients will be treated with Levodopa/carbidopa 4mg/kg/day in three divided 
doses (Dose determination outlined below). Patients and their families will be 
asked to submit the costs of medication to their insurance companies or cover 
the costs themselves, if this cost is not covered by their insurance. Per the UW 
Pharmacy, the pricing for 30 Carbidopa/Levodopa tablets is $27.81, the oral 
suspension would cost $32.32 for 100 mL.  Subjects under 135 pounds would 
require an oral suspension provided by the UW pharmacy, in order to control the 
appropriate dose. This formulation has been adapted from The Hospital for Sick 
Children (University of Toronto).  The ingredients for this formulation consist of: 
Carbidopa 25 mg/Levodopa 100 mg tablets (quantity = 5), Ora-Plus 50 mL, and 
Ora-Sweet 50 mL.  Subjects over 135 pounds could obtain the drug at an outside 
pharmacy. Treatment will continue for 3 months followed by a six day taper 
reduction in dose (3 days at twice per day and 3 days at once per day), as a 
rapid reduction in dosage can be associated with fever, stiff muscles, confusion, 
abnormal thinking, fast or irregular heartbeat, and sweating. Side effects reported 
in adults with Parkinson’s disease on Levodopa/carbidopa will be monitored (see 
schedule) and include nausea, headache, mood changes, insomnia, nightmares, 
dizziness, tiredness, leg pain, tinnitus and emesis. (These have not been 
reported in studies of Levodopa/Carbidopa in children) 
Based on a standard deviation estimate of logMAR from a study on ocular 
albinism patients (Wildsoet C.F., et al: Investigative Ophthalmology and Visual 
Science: 2000) of 0.23, a minimum of 44 patients is the required recruitment to 
find a treatment effect of 0.1 logMAR visual acuity with a paired T-test between 


 
7 
changes due to treatment powered at 80%..Anticipated recruitment would be 50 
patients total to allow for possible loss-to-follow-up and sufficient accrual. 
If a patient discontinues treatment early, the treatment and the reason will 
be documented, and they will be asked to still report for their data collection 
appointments.  If data is missing from the treatment phase, that patient will be 
unable to be used in the final analysis.  Hence, we plan to recruit extra patients to 
ensure full data from at least 44 patients.   
As previously mentioned, supportive measures are the only treatment 
modalities available to albinos, if a standard of care group were used it would be 
therefore, no treatment. The primary outcome is change from baseline, and since 
albinism is a chronic condition with no change in vision is the well-established 
natural history no standard of care group will be necessary – all patients enrolled 
will receive the standard supportive measures in addition to treatment.  
 
Treatment with Carbidopa in combination with Levodopa inhibits 
decarboxylation of peripheral Levodopa. Carbidopa does not cross the blood-
brain barrier and does not affect the metabolism of Levodopa within the central 
nervous system. Since its decarboxylase inhibiting activity is limited to extra 
cerebral tissues, administration of Carbidopa with Levodopa makes more 
Levodopa available for transport to the brain. Studies show Carbidopa saturates 
the bodies peripheral Dopa decarboxylase enzyme at approximately 70 to 100 
mg (1mg/kg/day) a day. Patients receiving less than this amount of Carbidopa 
are more likely to experience nausea and vomiting. This is the basis for the 
higher dose of 4mg/kg/day of Levodopa treatment in this study, at this dose the 
minimum amount of Levodopa would be available to the retina (a tissue 
protected by the blood-brain barrier), as the Carbidopa dose of 1mg/kg/day 
would reach a peripheral enzyme saturation level. This is the basis for the typical 
starting dose for treatment of Parkinson’s disease, but less than half the typical 
dose for treatment of DRD in children.  
 
Drug dosing: 
 
Levodopa dosages:  
 
Total daily divided 
tid (mg) 
weight lbs 
weight kg 
60 
25-33 
11-15 
75 
34-47 
>15-21 
100 
48-60 
>21-27 
125 
61-74 
>27-34 
150 
75-89 
>34-40 
200 
90-117 
>40-53 
250 
118-134 
>53-61 
300 
135-159 
>61-73 
4mg/kg/day 
>160 
>73 
 
 
Confidentiality: 
 
A physician or clinical technician trained in ophthalmology or 


 
8 
ophthalmologic photography will perform data collection during the clinical visit in 
a private setting. All procedures will be consented to. 
 
All records, including the data collection forms, will be coded numerically 
to keep the data separate from any patient identification. A log that includes the 
subject identification and assigned code will be stored independently from the 
data.  Data will be stored in a locked office or on an isolated hard-drive desk top 
computer which is password protected and can only be accessed by the PI. The 
hard drive of the PI is backed-up hourly. In addition, the study coordinator will 
have access to the paper charts used to monitor the treatment and adverse 
events.  No study data or subject logs will be stored on portable laptop 
computers. Photos will not be stored with study data, only reviewed from the 
medical record. 
 
Study Schedule: 
I --Pretreatment 
 
1 Informed Consent/Assent 
 
2 Blood pressure, heart rate, weight. 
 
Elevated blood pressure will need to be under control by the primary care 
provider prior to entry into the study.  
 
3 Ophthalmic Exam – complete with cyclopentolate 1% dilation (standard 
dilation drops used in the pediatric clinic in children over 20 pounds) 
 
 
a. Snellen visual acuity or HOTV 
 
 
b. Color vision Farnsworth 15 or 100 hue, patients old enough to 
participate (estimated 6 years old and up) 
 
 
c. Sweep visual evoked potential (VEP) (standard test in clinical 
setting -10 min test patients “watch a computer monitor” while recordings are 
made of vision response) 
d. Contrast Sensitivity (5 min test on contrast board) 
e. Color photography (Only performed If not current within the last 3 
yrs) (all photos and Optical Coherence Tomography (OCT) take 
about 10mins) 
 
predilation iris and full face 
 
postdilation fundus  
 
postdilation OCT 
 
 
 
4 Optional Blood draw for genetic subtype analysis – if unknown (5ml 
purple tube).  
 
 5 Females who are pregnant, lactating, or intending to become pregnant 
within the next 12 weeks.  A negative urine pregnancy test will be required 
for all females who have had a menstrual cycle.  
 
II – 1 day, 1 week and 1-month treatment – phone call check compliance, and 
adverse events. 
 
 
III -- 3 months treatment—prior to wash-out/weaning 
 
Drug count/compliance, adverse event monitoring. 


 
9 
 
1 Ophthalmic Exam – complete with dilation 
 
 
a. Snellen visual acuity or HOTV 
 
 
b. Color vision Farnsworth 100 hue 
 
 
c. Sweep VEP 
d. Contrast Sensitivity  
e. Color photography 
 
postdilation fundus 
 
postdilation OCT 
 
 
2 Blood pressure, heart rate 
 
3. Taper of medications over 6 days as outlined (3 days of twice daily 
dosing, then 3 days of once daily dosing). 
 
IV – 4-month 1 month post treatment 
 
1 Ophthalmic exam – nondilation 
a. Snellen acuity 
b. Color vision 15 Hue 
c. Sweep VEP 
d. Contrast Sensitivity 
 
Pharmacology: 
Carbidopa/Levodopa oral commercially available 
 
Storage:  Store at 25°C (77°F), excursions permitted to 15-30°C (59-86°F). 
Protect from light. 
Dosage: 4mg/kg/day Levodopa orally, 1mg/kg/day Carbidopa, in three equally 
divided doses. 
 
Disallowed medications:  
• Clorgyline 
• Iproniazid 
• Pargyline 
• Phenelzine 
• Procarbazine 
• Selegiline 
• Toloxatone 
• Tranylcypromine 
• Apomorphine 
• Bitolterol 
• Desipramine 
• Dobutamine 
• Dopamine 
• Epinephrine 
• Isocarboxazid 
• Isoetharine 
• Isoniazid 
• Isoproterenol 
• Linezolid 
• Methyldopa 
• Moclobemide 
• Nialamide 
• Norepinephrine 
• Venlafaxine 
• Bromperidol 
• Bupropion 
• Droperidol 
• Ferric Ammonium Citrate 
• Fosphenytoin 
• Indinavir 
• Iron 
• Kava 


 
10
• Metoclopramide 
• Phenylalanine 
• Phenytoin 
• Spiramycin 
• Phenothiazines 
• Risperidine 
• Tyrosine 
 
Rescue medication/overdose: Management of acute over dosage with 
Carbidopa Levodopa is the same as management of acute over dosage with 
Levodopa. Pyridoxine is not effective. 
General supportive measures should be employed, along with immediate 
gastric lavage. Intravenous fluids should be administered judiciously and an 
adequate airway maintained. Electrocardiographic monitoring should be 
instituted and the patient carefully observed for the development of arrhythmias; 
if required, appropriate antiarrhythmic therapy should be given. 
Clinical lab: none 
 
 
Data/Safety monitoring: 
 
Adverse events will be monitored by the study coordinator, who will record 
the events on AE collection forms, and report events upon discovery to the PI 
and co-investigators. Adverse events will be monitored at each visit, and during 
the phone interview on days 1, 7, and 30 after first dose of medication (see 
attached AE form) and patients/parents will be given the AE form and phone 
number of the study coordinator to report these events. The PI and co-
investigators will review each adverse event and confirm if it is related, serious, 
or expected.  Adverse event reports will be reviewed for possible trends, the PI 
and/or co-investigator would consider modifying or stopping the study in the 
event of an emerging pattern of events.  The study team will report such events 
to the IRB in accordance with the posted guidance.  If a patient is withdrawn from 
the study (either by themselves, a guardian, or the study staff) prematurely or the 
study is stopped, they will be contacted by phone to assure that the medication is 
tapered correctly (3 days at twice per day and 3 days at once per day) and asked 
to return for a post-treatment visit.  
 
Risks: 
 
Risks of entering this study arise from three potential areas. These 
potential areas are: 
 
• Medication risks 
• Clinical testing risks, and 
• Confidentiality risks 
 
As stated above, while this medication has not been tested by the FDA in 
children, however its use in children dates as early as 1993. In general, the side 
effect profile in patients without Parkinson’s disease (the primary FDA indication) 
is considerably less. Adverse events recording will include the 16 possible side 
effects reported in the literature. Subjects will be withdrawn from the study and 


 
11
instructed on tapering of medication if the AE is of significant severity that the 
subject, their guardian, or the PI feel continuation is not justified. Please see AE 
reporting form.  
 
Risks from testing: Patients will undergo a complete ophthalmic exam 
twice in three months. Children under 7 have this every 6 months and over 7 
yearly. Standard, but more invasive testing procedures include: VEP, 
photography, and OCT. Visual Evoked Potential (VEP) testing is an 
electrophysiologic recording of brain wave activity similar to EEG recording that 
takes 10 minutes while subjects watch a computer screen. This test is performed 
routinely (30 times/wk) on preverbal patient in the clinic and is very well tolerated. 
Photography and OCT (a form of photography) requires subjects look into the 
camera while image is captured -- each image is recorded in less than 5 
seconds.  
 
Finally, every safety measure will be put into place to limit breaches of 
confidentiality. Patient confidentiality has been discussed in several areas of this 
protocol and include, but are not limited to:  genotyping results, pregnancy testing 
of minors, and clinical documentation of visual performance including 
photographic information. 
 
 
Statistical: 
 
 
  
The primary analysis will be to look at the paired differences of the 
changes in logMAR due to 3-month treatment for each subject when compared 
to baseline. Sample size calculations based on finding a 0.1 logMAR difference 
in visual acuity at 95% confidence, with a standard deviation of .23, shows a 
minimum sample size of 44 patients needed to find a significant effect with 80% 
power. Other investigators have used the .2 logMAR vision improvement as 
marker of utility of vision improvement.6  
 
This study will have an intent to treat goal. Anyone that fits the 
inclusion criteria for the study regardless of baseline logMAR vision or OCA type 
will be entered in the study.  The goal will be to have 50 patients to ensure at 
least 44 patients in treatment, after any possible dropouts. Stopping criteria for 
enrollment will be a total recruitment of 50 patients, additionally after 22 patients 
(half) complete the course of treatment, the data will be analyzed for potential 
benefit. If significant results are found, the trial will be concluded. 
 
Data from 19 completed subjects was analyzed. The standard deviation of 
differences of logMAR (from baseline to on-treatment) has been estimated to be 
0.085. Using a more conservative estimate of 0.1, a one-sample t-test with a 
significance level of 0.05 and power of 80% would be able to detect a difference 
of 0.053 when 30 subjects are included in the trial. Hence, 30 subjects will enable 
us to achieve enough power to confidentially test for changes of 0.1 logMAR.  
 
 
 
Data collection: 
 
A physician or clinical technician trained in ophthalmology or 


 
12
ophthalmologic photography will perform clinical data collection during the clinical 
visit in a private setting. All procedures will be consented to. Results of research 
testing (genotyping and pregnancy testing) will be kept in a study chart; results of 
clinical test will be recorded in the UW clinical chart and study chart. Additionally, 
all the data collection forms will be coded numerically to keep the data separate 
from any patient identification.  
 
Genotyping (5cc purple top tube) 
All tubes will be labeled with a study patient ID number, drawn at the University 
Station lab. Upon receipt at the central laboratory (Casey Oregon) the lab 
coordinator will remove the blood from the tubes and transfer it to the centrifuge 
for DNA extraction.  All DNA samples will be held for only 6 months after 
completion of the study, in the event the testing would need to be validated, and 
labeled only with study ID number, a number that cannot be identified with a 
particular individual by anyone outside of the study clinical center at the 
UW.  Casey eye institute will not be using DNA for any additional purposes. 
 
Urine pregnancy testing will be performed anonymously by the UW lab 
and resulted to the study coordinator within one hour. 
Labeling Procedures 
Specimen labels will be provided to the clinic by the Study Coordinating Center. 
Each set of labels will have a unique 5-digit random specimen identification 
number that will be pre-printed on the labels. The date the sample was drawn will 
be completed by the clinical center at the time the specimen is obtained. No 
other markings will be placed on the specimen or its container that contain 
personally identifying information. 
All study patient records and data with study patient ID numbers and 
name codes are stored independent from the data, in a locked office at 2880 
University Ave. Madison.  The clinic coordinator and PI have access to records. 
 
No study data or subject logs will be stored on portable laptop computers. 
Photos and electrophysiologic raw data will not be stored with study data, only 
reviewed from the medical record. Identifiers and study data will be kept for five 
years after the conclusion of the study. 
 
References: 
1) Abrams LS and Traboulsi EI. Albinism.  In Genetic Diseases of the Eye. 
(1998) Oxford University Press.  
 
2) Kwon BS, Haq AK, Pomerantz SH, Alban R (November 1987). "Isolation and 
sequence of a cDNA clone for human tyrosine’s that maps at the mouse c-
albino locus". Proc. Natl. Acad. Sci. U.S.A. 84 (21): 7473–7. 
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