Bascom Palmer Eye Institute - Neuro-Ophthalmology

Neuro-Ophthalmology

What about Leber Hereditary Optic Neuropathy research?

Leber hereditary optic neuropathy (LHON) is a rare genetic eye disease that usually affects men between the age of twenty and forty but sometimes symptoms can occur at any age in men or women. LHON is inherited from the female (maternal) side of the family and causes permanent visual loss in young adults. The most common symptoms start with blurring or loss of vision in one eye that gradually worsens over a period of weeks. Within a few months the other eye is very likely to become affected, with both eyes suffering significant visual loss.

Characterization of the hereditary nature of LHON led early researchers to postulate that it was a disorder of mitochondrial inheritance. Molecular analysis has confirmed that the basic etiology results from a point mutation in the mitochondrial DNA. Three primary mutations at nucleotide pair 3460, 11778, and 14484 are generally agreed to be the primary causes of LHON, accounting for a large majority of LHON cases. To date an effective treatment for LHON has not been identified.

LHON is a worthy target for mitochondrial gene therapy, and we are currently actively working on developing gene therapy for LHON.

OBJECTIVES OF THE STUDY
The major aim of this study is to identify and clinical characterize a group of patients and carriers with LHON due to G11778A mutation in preparation for a future gene therapy study. The intent is to eventually choose subjects for the future phase 1 or phase 2 of the gene therapy study from the participants in this preparatory phase of the study.

DESCRIPTION OF THE STUDY
There are two phases to this study: the diagnosis confirmation phase and the follow up phase.
Your participation in the main phase of the study will last approximately 4 weeks from the time you enter the study. During the main part of the study, you will have a screening (or baseline visit) and if you are eligible for the study, you will be asked to have a blood sample taken for DNA analysis to confirm the diagnosis of the most common genetic change (G11778A LHON mutation) that causes LHON.

If the results are negative for the most common genetic change (G11778A LHON mutation) that causes LHON. we will direct you back to your referring doctor or if you wish, you may be seen in our clinic. If the DNA results return positive for the most common genetic change (G11778A LHON mutation) that causes LHON. you will be asked to participate in the follow up phase of the research study that will last approximately 4 years.

During the follow-up phase you will be asked to return to the clinic for 8 scheduled office visits: Month 6 (Visit 1), Month 12 (Visit 2), Month 18 (Visit 3), Month 24 (Visit 4), and Month 30 (Visit 5), Month 36 (Visit 6), Month 42 (Visit 7) and Month 48 (Visit 8).

The total length of your participation in the study could last up to 4 years (including both the main and follow-up phases).

WHAT IS INVOLVED IN THE STUDY?
All of the procedures listed below are offered to the affected LHON person and maternal family members who do not have any symptoms of LHON, because this condition is maternally inherited. These procedures are not standard of care for family members of patients with LHON. The results of these procedures on family members are helpful to further the understanding of this condition.

During the screening visit, you will be asked about your general health, your medical history and about any medications you regularly take. You will have a number of tests to measure your vision including visual acuity, visual field, measurements of intraocular pressure, slit-lamp biomicroscopy (a detailed examination of the eye with a standing microscope), ophthalmoscopy (tests where the physician examines the inside and outside of the eye with a light source), fundus photography (photographs of the optic nerve and retina), optical coherence tomography (an imaging test that lets the physicians see inside the eye), and electroretinogram (a test that measures electrical signals from the eyes).

If you are eligible to take part in this study and would like to participate, a DNA blood sample may be collected to see if you have the same genetic change as the affected family member. For this, a blood sample for genetic testing will be taken and sent to a laboratory to test for the most common genetic change (G11778A LHON mutation) that causes LHON.
If the results are negative for the most common genetic change (G11778A LHON mutation) that causes LHON, we will direct you back to your referring doctor or if you wish, you may be seen in our regular clinic.

If the DNA results return positive for the most common genetic change (G11778A LHON mutation) that causes LHON, you will be asked to participate in the follow up phase of the research study.

If you decide to participate in the follow-up phase of the study you will be asked to return in Month 6 (Visit 1), Month 12 (Visit 2), Month 18 (Visit 3), Month 24 (Visit 4), and Month 30 (Visit 5), Month 36 (Visit 6), Month 42 (Visit 7) and Month 48 (Visit 8).

Eye examination and collection of blood samples

During each of these visits you will be asked about your Medical History (Detailed questions about your medications, past surgeries, health problems, and symptoms).

You will also have a number of tests on your vision including:

Dilated Exam: The pupil (black part of eye) is enlarged with eye drops so the back of the eyes can be examined.

Visual Acuity: Measurement of how well you see by reading letters on a chart.

Slit Lamp Examination: The eye is checked with a lighted microscope.

Intraocular Pressure (IOP): Pressure inside the eye is measured by touching the eye with a small probe after the eye has been numbed with eye drops.

Automated Visual Field: Your peripheral (side) vision is measured by the way you respond to lights that are produced by a computerized machine.

Pupil reactivity: Check the pupils for reactivity to light and near stimulus.

Optical Coherence Tomography (OCT): A machine sends beams of light through the pupil that reflect off the retina and back into the machine. It displays a picture of the structures inside the eye.

Fundus Photography: Photographs of the optic nerve and retina.

You may have tests on your retina, known as pattern electroretinogram (PERG): A clinical non-invasive test that records electrical activity in the eye.

In addition, blood samples will be obtained at these time points to be tested for the presence of signs of optic nerve damage. (PNF-H test)

Genetic counseling: Dr. Lam/Dr.Guy will explain all aspects of the genetics, prognosis of the disease, lack of any effective treatment for LHON and current research in the field applicable to the cause of this disease and future treatments.

The research in this study is not based on the tests that an individual has done, but is based on the group analysis of the results from all of the participants.

COSTS FOR PARTICIPATING IN THE STUDY
If you are a patient with LHON and have no insurance, the study will pay all expenses involved in the study including genetic testing, clinical examination, and clinical testing.

If you are a patient with LHON and have insurance, your insurance will be billed for examination and testing that are considered standard of care, and the study will pay for examination and testing that are not considered standard of care. For the Initial visit, the cost for Genetic testing will be billed to your insurance provider. For the initial visit, 12 month visit, 24 month visit, 36 month visit, and 48 month visit, the cost for a routine eye examination, visual field testing, optic nerve photography, optical coherence tomography, will be billed to your insurance provider. You will be responsible for your own co-pay/deductible payments. For the 6 month visit, 18 month visit, 30 month visit, and 42 month visit, the study will pay all expenses involved for clinical examination and testing. The study will pay for the pattern electroretinogram for all visits. If your insurance refuses to pay for the clinical examination, genetic testing, and clinical testing billed as mentioned, the study will pay for the examinations and the testing refused by your insurance.

If you are a family member of a LHON patient, the study will pay all expenses involved in the study including genetic testing, clinical examination, and clinical testing. Your insurance will not be billed. Should you develop LHON, your insurance will be billed for examination and testing that are considered standard of care, and the study will pay for examination and testing that are not considered standard of care.

INCLUSION CRITERIA

Males or Females with molecularly proven G11778A LHON.
Asymptomatic family members of LHON patients.
Participants must be in good general health.
Participants must be able to provide written informed consent for the study and consent for DNA testing.

EXCLUSION CRITERIA

Ocular: No pre-existing eye conditions that would preclude surgery or interfere with the interpretation of any surgical complications (e.g. glaucoma, corneal and lenticular opacities).
Systemic: No complicating diseases; any condition which would not allow the patient to complete follow-up examinations during the course of the study; medical conditions causing immunosuppression (e.g. chemotherapy, HIV disease, chronic steroid therapy) or chronic infection (e.g. mycobacterium).

RECRUITMENT
Subjects will be examined at the Bascom Palmer Eye Institute outpatient clinics in Miami.

Sponsor
National Eye Institute (NIH)
Bethesda, Maryland
United States

Investigator
Byron L. Lam, M.D. / John Guy, MD
900 NW 17th Street
Miami, Florida 33136
United States

FREQUENTLY ASKED QUESTIONS:

Why is this study being done?
The purpose of this study is to identify and follow a large number of LHON patients and their family members (who have not lost vision in either eye) in a normal clinic setting over a period of 4 years. With a large number of subjects, we hope to evaluate the long-term course of visual function in patients with LHON and to develop a course of treatment of visual function. The intent is to eventually choose subjects for the future phase 1 or phase 2 of the gene therapy study from the participants in this preparatory phase of the study.

How many subjects will take part in the study?
Approximately 50 subjects will participate in this study. While you take part in this study, you may not take part in any other research studies with an investigational drug, device, or procedure.

Are there any fees that I need to pay if I have no insurance?
The study will pay all expenses related to the study whether you are an LHON patient or a family member to an LHON patient.

Are there are any fees I need to pay if I have insurance?
If you are a patient with LHON and have insurance, your insurance will be billed for examination and testing that are considered standard of care, and the study will pay for examination and testing that are not considered standard of care. For the Initial visit, the cost for Genetic testing will be billed to your insurance provider. For the initial visit, 12 month visit, 24 month visit, 36 month visit, and 48 month visit, the cost for a routine eye examination, visual field testing, optic nerve photography, optical coherence tomography, will be billed to your insurance provider. You will be responsible for your own co-pay/deductible payments. For the 6 month visit, 18 month visit, 30 month visit, and 42 month visit, the study will pay all expenses involved for clinical examination and testing. The study will pay for the pattern electroretinogram for all visits. If your insurance refuses to pay for the clinical examination, genetic testing, and clinical testing billed as mentioned, the study will pay for the examinations and the testing refused by your insurance.

If you are a family member of a LHON patient, the study will pay all expenses involved in the study including genetic testing, clinical examination, and clinical testing. Your insurance will not be billed. Should you develop LHON, your insurance will be billed for examination and testing that are considered standard of care, and the study will pay for examination and testing that are not considered standard of care.

Who covers for traveling expenses?
You will not be paid for your participation in this study. You will not be reimbursed for parking and travel expenses.

Will I benefit from this study?
By studying a large number of individuals with LHON, we expect to learn more about the changes in vision and degeneration of the retina and optic nerve in order to treat this rare eye disease over time.

You will not receive any direct medical benefit from participating in this particular study, but an indirect benefit is that the National Institute of Health grant supporting this study is designed to bring gene replacement therapy out of the laboratory to patients with Lebers hereditary optic neuropathy caused by the most common genetic change (G11778A LHON mutation) that causes LHON. Patients screened as part of this study may be asked to be subjects in a future research study of this gene therapy. This may include you or your family members who have the genetic mutation. Even though they do not have visual loss, 50% of the males and 10% of the females will develop visual loss and could be potentially protected by gene replacement in a future clinical trial; so there may be direct benefit for the family member.

Will I be receiving any treatment for my condition during the study?
There is no treatment of any kind in this preparatory phase of the study, but Patients screened as part of this study may be asked to be subjects in a future research study of this gene therapy. This may include you or your family members who have the genetic mutation.

How often do I need to come during the year?
The study will last for four years, and you need to come two times a year (every 6 monhts).

How much time will I need for my appointment?
It will take all day, usually the visit start at 8 am and lasts until 5 pm.

Where should I go the day of my appointment?
Bascom Palmer Eye Institute
900 NW 17th Street - Fourth Floor
Miami, Florida 33136

If I need to reschedule, who could I contact?
Alexis Morante
Bascom Palmer Eye Institute at the University of Miami Miller School of Medicine
Phone 305-202-4731

Which of my family members would be good candidates to participate in the study?
Maternally-related family members who do not have any symptoms of LHON, because this condition is maternally inherited.

When will I know if I qualify for this study?
One month after the Initial Visit.

What is the total length of the study?
The total length of your participation in the study could last up to 4 years.

What are the risks of this study?
The risks of blood drawing are minimal. They include fainting, pain and/or bruise at the site of puncture. Rarely, infection or the formation of a small clot or swelling of the vein and surrounding area may occur.

Your near vision will be blurred for 4-6 hours after having your eyes dilated, and you may be sensitive to bright light during this time as well. You should have someone accompany you to your appointment and you may want to wear sunglasses to reduce any discomfort to bright light.

Will I be paid for participating?
You will not be paid for your participation in this study. You will not be reimbursed for parking and travel expenses.

Can I drop out of the study at any time?
Your participation in this study is voluntary. You may decide not to participate or you may leave the study at any time. Your decision will not result in any penalty or loss of benefits to which you are entitled. The study doctor or sponsor may also remove you from the study at any time without your consent if he/she feels it is in the best interest for you medically, or for administrative reasons.

Who can I contact if I have any other questions?
Study doctors will be happy to answer any questions that you may have regarding this study plan. You may call Byron L. Lam M.D. 305-326-6021 or Alexis Morante, study coordinator, at 305-202-4731 to have any questions regarding this study answered.

Who will provide funding?
Funding for this research study is provided by the National Eye Institute (NEI).

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