A Family Affair

An additional 10,000 people in New Zealand are affected by age-related macular degeneration. It is the leading cause of vision loss in older adults. Complex mixtures of genetic and environmental factors are thought to play a role in this disorder. For people with this type of retinal degeneration, the booklet A New Zealand Guide to Age-Related Macular Degeneration is available from Retina New Zealand.

Dedicated to saving sight.

Retina New Zealand is a consumer group of the Royal New Zealand Foundation for the Blind. Retina New Zealand is an incorporated society created to help those who are visually impaired due to retinal degeneration.

Retina New Zealand is committed to:

Foreword
By Dr Dianne Sharp

It has been my privilege to be associated with Retina societies in Great Britain and New Zealand and to know many people working in the field of retinal degeneration research. One factor has been common -commitment!

Some years ago one man who was affected with retinitis pigmentosa had a dream: to promote research to find a cure for this disorder and to offer support to other people who were affected with retinal degeneration. Retina International is now a large organization that encompasses a range of retinal degenerative conditions with 23 member countries. These national Retina societies are patient organisations that not only offer mutual support but also are the catalyst for major scientific studies and discoveries in this field. This book is a tribute to Retina New Zealand. Its enthusiasm and commitment to helping others understand this complex group of disorders is evident.

When an ophthalmologist makes the diagnosis of inherited retinal degeneration it is often difficult to answer all the questions at once. We now have a book that has been written for patients and their families and it addresses the most commonly asked questions about inherited retinal degeneration. It will be a valuable tool,helping to build the communication lines between patients,medical staff and researchers.

Dianne Sharp Mb CHB,FRACS,FRACO
Consultant Ophthalmologist,Auckland Hospital

How does the retina work?

The eye is like a camera (see the diagram above). The lens system at the front of the eye consists of the CORNEA and the LENS and focuses light onto the RETINA which lines the back of the eye and acts like the photographic film in a camera. The retina contains the eye 's light sensitive receptor cells which can record images focused on it, process those images instantaneously and respond automatically to changes in light levels, functioning like a TV camera.

The PHOTORECEPTORS come in two varieties and each has a different function. Six million CONES record colour vision and are concentrated in the MACULA ,the central 10 degrees of the retina. Three types of cones enable us to discern over 150 colours and countless shades of those colours. The macula allows us to see fine detail clearly and is needed for tasks such as reading small print.

One hundred and twenty five million RODS are responsible for sight in very dim light. The rods are also important for detecting movement in our peripheral vision.

Each photoreceptor contains stacks of discs containing pigment molecules. These pigments consist of a protein component called opsin that is joined to a derivative of vitamin A. Light stimulates the pigment molecules to undergo a series of chemical changes that ultimately result in triggering a nerve impulse to the brain. Groups of rods and cones are organised within the retina to convert the stimulus into meaningful patterns which are then transmitted via the OPTIC NERVE which acts as a telephone cable, bringing coded visual information to the brain for further processing.

The stacks of discs are continually broken down and renewed by the PIGMENT EPITHELIUM . These cells form the outermost layer of the retina and are responsible for delivering nutrients to the photoreceptors and for collecting and removing wastes from those cells. The pigment epithelium is therefore essential for healthy photoreceptors.

What is inherited retinal degeneration?

Inherited retinal degeneration (RD)is the term for a group of hereditary conditions that affect the retina or light sensitive layer at the back of the eye.

It is estimated that there are 1,000 people affected with inherited RD in New Zealand and it is possible that there are as many as 3 million people affected with inherited RD worldwide.

The common feature is the gradual deterioration of the retina for one reason or another. Even within a particular clinical diagnosis such as Usher syndrome or Leber congenital amaurosis, there may be a number of similar but different disorders.

The rate of deterioration is variable. While some forms of RD may cause significant visual problems, other forms are very mild and may be merely an inconvenience. For example, children may be severely affected by Leber congenital amaurosis whereas adults with some forms of retinitis pigmentosa maintain reasonable vision into retirement.

For specific information concerning your own retinal condition, it is important to consult an ophthalmologist and/or medical geneticist. You may be referred for special tests to find out what particular type of RD you have.

How retinal degeneration affects eyesight

In some disorders the entire retina is affected while other conditions involve only the retina used for central vision.

Common symptoms are difficulty with night vision and loss of peripheral visual field in retinitis pigmentosa while macular degeneration causes loss of central (reading)vision.

Additional disorders of the eye may arise as a complication associated with retinal degeneration. For example,some patients with retinitis pigmentosa may also develop cataracts and/or macular degeneration.

Retinitis Pigmentosa (RP)

Most people with retinitis pigmentosa can distinctly remember difficulty seeing at dusk or at night during childhood and over time the symptoms become more noticeable.

Retinitis pigmentosa is normally diagnosed between the ages of 10 and 30 years. It is usual at this stage for the person with retinitis pigmentosa to become aware of progressive visual loss on the outer edges of the field of vision. This is particularly so in dull light, when many people become disorientated and do not like to go out of their homes unaccompanied. The loss of side vision is gradual and irregular, and many people do not become aware of the problem until they begin tripping over low objects or banging into door jambs. They have difficulty driving and walking at night. Some people may also have difficulty in reading, caused by deterioration of central vision.

Macular degeneration

Macular degeneration is due to changes occurring in the macula. It reduces vision in the central part of the retina but it does not affect peripheral or side vision. Retina New Zealand has a separate booklet concerning macular degeneration.

Stargardt disease is an inherited macular degeneration that occurs in young people. Age-related macular degeneration occurs in many older people and may be regarded as part of the body 's natural aging process or as a distinct disease process. Two major clinical sub-groups are recognised: the 'dry ' ((atrophic)and the 'wet ' ((exudative forms). Complex interactions between multiple environmental and genetic factors are thought to cause these disorders.

Visual support services

A person with a retinal degenerative condition may progress to the point where there is a need for orientation and mobility instruction, special equipment and training for persons with a vision impairment. Advice may be obtained by contacting Retina New Zealand or any branch of the Royal New Zealand Foundation for the Blind.

What are the inheritance patterns?

Genes are the tiny molecules that determine all our hereditary characteristics.

They are situated on the strands of DNA that make up the chromosomes present in the nucleus of every cell in our body. Humans have about 30,000 different genes distributed along the 23 pairs of chromosomes. The first 22 pairs of chromosomes are numbered according to size from 1 (the largest) to 22 (the smallest). These chromosomes are called the autosomes.

The 23rd pair of chromosomes are the sex chromosomes. Women have two X chromosomes while men have one X chromosome and one Y chromosome. This is what differentiates the sexes.

For each chromosome pair, one chromosome is inherited from the mother and a second chromosome from the father. A child, therefore, receives half its genetic material from its mother and half from its father. Whether the child is a boy or a girl is determined by whether he or she receives a Y chromosome or an X chromosome from the father 's sperm cell.

When retinal degeneration genes are passed on from parent to child, they may act in either of two ways. A dominant gene will cause retinal degeneration even in the presence of a healthy version of that gene. A recessive gene will only cause retinal degeneration in the absence of a healthy version of that gene. Depending upon whether the gene is located on an autosomal chromosome or on the X chromosome, four broad types of inheritance pattern are commonly observed.

1. Autosomal Dominant
2. Autosomal Recessive
3. X-linked Recessive
4. Sporadic or no family history

Autosomal Dominant RD (see TABLE 1)

In autosomal dominant conditions,an affected individual has one defective gene and one healthy gene for a particular gene pair. Each child of an affected parent has a 50% chance of inheriting the defective gene in which case the child will usually also be affected. Similarly there is a 50% chance of inheriting the healthy gene from the affected parent in which case the child will have normal vision.

The autosomal dominant inheritance forms of retinitis pigmentosa make up about 20% of all affected people and are confined to relatively few families. The disease tends to be milder than the other types and slower in its progression.

In autosomal dominant conditions, there may be a clustering of family members affected through consecutive generations. Both females and males can be affected. Moreover a female or male affected parent can pass the affected gene on to children of either gender.

The analysis of autosomal dominant retinal degeneration is complicated by the fact that the clinical manifestations or penetrance of the gene may not be 100%. In other words, a family member can be very mildly affected or clinically free of the disease and yet have a parent and child affected. This occurs in perhaps 10% of autosomal dominant retinitis pigmentosa families.

Autosomal recessive RD (see TABLE 2)

We all carry large numbers of autosomal recessive genes for all manner of conditions. It is only when your partner or spouse carries a recessive version of the same gene as you do,that your children may have the condition caused by a deficiency in this gene.

Autosomal recessive retinal degeneration affects males and females equally. This form is the commonest inheritance type for retinitis pigmentosa accounting for about 30% of cases. A number of different autosomal recessive retinitis pigmentosa genes and a gene for Stargardt macular degeneration have already been identified by genetic laboratory scientists.

Autosomal recessive retinal degeneration most commonly occurs when both parents have normal vision but are carriers for recessive versions of the same retinal degeneration gene. There is often no previous family history of inherited retinal degeneration. Marriage between close relatives is customary in some cultures and in that situation the condition may occur scattered throughout the extended family.

If both parents are carriers, then for each child from that relationship, there is a one in four chance of being affected by retinal degeneration. The affected child will have inherited a recessive version of the gene from both parents. There is a two in four chance that a child may be a carrier and there is a one in four chance that a child may be unaffected. The inheritance is random and the odds are the same as when tossing two coins in the air and seeing which way they land.

If a parent is affected by autosomal recessive retinal degeneration, the children will usually be unaffected carriers. If the other parent is affected by, or is a carrier for, autosomal recessive retinal degeneration caused by the same gene, their children may be affected.

X-linked recessive RD (see TABLE 3)

With this inheritance pattern,only males are affected and females are carriers of the condition. An example of an X-linked retinal degenerative condition is choroideremia. X-linked recessive inheritance accounts for about 10%of all retinitis pigmentosa patients. This is also the mechanism of transmission of colour blindness and the bleeding disease, haemophilia, both of which occur in males.

As mentioned earlier, females inherit one X chromosome from each parent whereas males inherit an X chromosome from their mother and a Y chromosome from their father.

When a recessive gene occurs on the X chromosome, males do not have another copy of that gene, ie they have no backup copy. In the absence of a healthy version of that particular gene, a male will be affected by retinal degeneration.

By contrast females who have inherited a recessive X chromosome gene usually inherit a healthy gene from the other parent. Such females usually have normal or near normal vision. Ophthalmological examination can detect abnormalities in some carriers.

An affected male will pass on the recessive X chromosome gene to each of his daughters and they will be carriers. An affected male will pass on his Y chromosome to each of his sons. Provided the sons inherit a healthy X chromosome gene from their mother, they will have normal vision.

For a carrier woman, children of either sex have a 50%chance of inheriting the healthy X chromosome gene and having normal vision. If a child inherits the recessive X chromosome gene from their mother and a Y chromosome from their father, they will be an affected boy. If such a child instead receives a healthy X chromosome gene from their father, they will be a carrier daughter.

Sporadic or simplex cases

Even after appropriate investigations to categorise the above three patterns of inheritance, many cases of RD cannot be categorized because there is no previous history of the disease. Sporadic RD can occur from the following situations.

1. Random occurrence of Autosomal Recessive RD from the chance union of two carriers.

2. A new mutation that is often dominant but could be any of the three above groups.

3. A male with sporadic RD may have X-Linked Recessive RD transmitted from previous generations through female carriers.

Genetic counselling

It is important that all people with inherited RD and their families understand the genetics of their own condition and the probability of passing it on to their children.

Some forms of inherited RD are associated with conditions affecting other organs forming syndromes. For example Usher syndrome involves retinitis pigmentosa plus hearing loss. It is beyond the scope of this booklet to outline details of the many neurological, muscular, metabolic and kidney conditions that can be associated with progressive impairment of rod and cone function. Most of the syndromes are of recessive inheritance and require expert assessment.

A genetic assessment requires accurate clinical diagnosis. A detailed examination by an ophthalmologist, and possibly by other medical specialists, is an important part of the process. Although some ophthalmologists are prepared to give detailed genetic counselling, many prefer to pass the task on to a hospital genetic service. Your GP or eye professional can refer you to a hospital genetic service. Or you can contact the service directly via a hotline.

At present the hotline contact numbers are:

Auckland Genetic Hotline
Phone 0800 476 123

Wellington Genetic Hotline
Phone 0508 364 436

Christchurch Genetic Hotline
Phone 0508 364 436

(South Island callers ask for Dr Caroline Lintott)

Before 1971 little or no research had been undertaken into retinal degeneration. Now major research is being carried out in many countries, largely because of the stimulus provided by the Retina societies.

Here in New Zealand, a research group at the University of Otago has been carrying out gene mapping research since 1989. The project involves searching for genes that cause autosomal recessive forms of RD. It is funded by diverse sources including the government (Health Research Council), community (Lottery Grants Board) and Retina societies (New Zealand, Australia and United States).

Considerable progress has been made in identifying and understanding the genes responsible for inherited RD. Over one hundred different genes have been implicated to date. The areas of active research include retinal biology, ophthalmology, transplantation of healthy retinal tissue,pharmaceuticals, gene therapy and retinal implants.

The causes of RD are numerous, so it is unlikely that a single treatment will emerge to slow down the progress of all forms of retinal breakdown. Many ideas have been tried and in some cases proof of principle has been established in animal models. There remain considerable obstacles to overcome. However there is now hope for people affected with RD that therapies will soon be devised and solutions will be found at some stage in the future.

Each member country of Retina International must have a Medical and Scientific Advisory Board recognised by Retina International. Their function is to assess research projects and advise on scientific matters relating to retinal degeneration. Members from each country 's Scientific and Medical Advisory Board may participate in the Retina International Scientific and Medical Advisory Board.

The New Zealand Scientific and Medical Advisory Board includes:

Dr Rachel Barnes, opthalmologist
Dr Michael Denton, genetic researcher
Dr Joanne Dixon, medical geneticist
Dr Carolyn Hope, ophthalmologist
Dr Toni Marks, psychiatrist
Dr Marion Maw, genetic researcher
Mr Gordon Sanderson, optometrist
Dr Dianne Sharp, ophthalmologist
Dr Andrea Vincent, opthalmologist/medical geneticist

The newsletter and website of Retina New Zealand (www.retina.org.nz)carries regular updates on research developments. In addition the following websites are useful:

Retina International www.irpa.org

US Foundation Fighting Blindness www.blindness.org

Your questions answered

It is essential that all members of your family, and your friends, receive accurate information so they can understand what is happening to you. Without this they may not comprehend your situation and may not be able to give you the support you need. You should explain what your limitations are in a particular situation such as coping with changes from shadow to sunshine and sunshine to shadows. A sense of humour on all sides certainly helps.

How rapidly does sight diminish?

The rate of sight loss is different for each person and can be assessed by an eye specialist. If the disorder runs in a family, the pattern may be similar within the family. There is usually a gradual degeneration, so that in most cases there is time to come to terms with the change in vision. Any deterioration often occurs in a stepwise fashion with long periods showing no change.

Does RD lead to blindness?

Most people think that blindness is complete loss of vision. Some people with retinitis pigmentosa may become blind. Most retain some sight, however,all their lives. Macular degeneration affects central vision only; people with inherited macular degeneration retain peripheral vision throughout life.

What about cataracts?

Many people with retinitis pigmentosa develop cataracts that cause cloudiness in the lens of the eye. The lens can be surgically removed and replaced with an implant but whether or not the vision will be improved depends on the extent of the RD and the success of the cataract surgery. This should be discussed with an ophthalmologist.

Does night blindness mean RD?

No. Night blindness alone does not necessarily represent a progressive eye disorder. However, anyone suffering from this should be tested for retinal disorders as a precaution.

There are times when my vision seems better or worse. Does this happen to others?

There are a number of factors which might account for good days or bad days. Some people see better on cloudy or dull days. Vision is a function of the brain. We all know that we are more alert at some times than at others. Some people may not see as well when tired or under emotional strain. All people have days when they seem to function better or worse than on others.

Does light have an effect?

There is no scientific evidence to suggest that normal light levels affect or worsen the symptoms of retinal breakdown. It is advisable to protect the eyes from long exposure to bright light, particularly ultra violet, simply as a precaution. Suitable sunglasses may be obtained from the Royal New Zealand Foundation for the Blind. Otherwise you can use your sight normally without fear of damaging it.

Does pregnancy affect RD?

There is no evidence that pregnancy or childbirth will accelerate the RD progression.

Can RD be easily diagnosed?

This depends on the type and extent of the condition. A characteristic change in the appearance of the retina may be visible to the ophthalmologist. A proper eye examination is needed to determine the precise state of the retina. A visit to a specialist is advised. Here the field of vision will be tested, the central vision measured (visual acuity) and an electroretinogram (ERG) test may be performed. This test measures the electrical activity of the retina and how it changes with light. Electrical tests of retinal function can lead to a diagnosis at a very early stage of the disease. Alternatively, these tests can show that a family member is not affected, offering reassurance for the future. These tests,with a careful analysis of the family tree or whakapapa will help classify the type of RD. For details of genetic counselling available in your area see page 17.

If a child is diagnosed as having RD, when and what should I tell him or her?

There is no hard and fast answer to this. Children have varying needs dependent on their age and maturity. Although they are often perceptive and sense that there is a problem, they may be capable of absorbing only a little information at a time. Answer questions frankly and positively, not giving more information than your child has requested. Help him or her to come to terms with the problem, but do not panic or become overprotective. Do not let children use this problem as an excuse for not fulfilling their full potential. A parent may find it helpful to discuss the difficulties with other parents who have faced, or are facing, similar problems. Your local branch of Retina New Zealand may be able to help you in this regard. Professional advice may also be necessary.

Does progressive loss of vision mean that I will become dependent?

There are a growing number of aids, both optical and electronic, which make life easier for those with visual problems. There are aids to help mobility, special lighting and equipment to help at work or in the home. Generally people affected with RD can manage almost as independently as anyone else. There are also organisations like the Royal New Zealand Foundation for the Blind which can help. The Retina New Zealand branch in your area can refer you to the resources available.

Is it common to experience emotional distress after RD is diagnosed?

Yes. After hearing for the first time that you have some form of retinal degeneration which may lead progressively to blindness, it is not unusual to experience fear and confusion. Some people accept the situation more easily than others. Some go through a temporary period of depression before they come to terms with the situation. In addition to frustration and depression, the feeling of being alone is apparent. However, you are not alone. Retina New Zealand, its branches and its members are there to support all people affected with retinal degenerative conditions and their families, to pass on information and keep abreast of research developments.

What are low vision aids?

Low vision aids are designed to enable people to make the most of the eyesight they have. Each person is different with differing needs. Lenses, magnifiers, monoculars, closed-circuit televisions or other sophisticated electronic equipment may help. Information on such aids is also available through Retina New Zealand and the Royal New Zealand Foundation for the Blind, and there may be a Low Vision Clinic nearby. Some of the aids are expensive but loans or subsidies are available through the Royal New Zealand Foundation for the Blind once you have been registered with them as a member. They offer appropriate rehabilitation as well as aids and appliances.

What about my career?

People with RD continue to lead very productive lives. There are examples of successful careers in law, management, education, social work, accounting, computing, tourism, and other diverse occupations. After coming to terms with the disorder and finding the right aids, equipment and training, difficulties can be overcome. With perseverance a suitable career can be found.

Can I go on driving my car?

Make a responsible decision and be guided by expert opinion. Do not wait until you have an accident.

Will I need help with mobility?

You may not need help at first, but later on, with training you can overcome most mobility problems. This may include using your vision more efficiently, or using a white cane or guide dog. People with macular degeneration may benefit from training in the use of eccentric viewing, that is, the greater use of side or peripheral vision.

Can things at home be improved?

Yes. A great deal can be done by careful use of lighting, colours, contrasts, textures, labelling, and so on. Train yourself and your family to be tidy and methodical. Special attention should be paid to safety in the home. There are lots of aids to help with cooking, gardening, and do-it-yourself projects. Information is available from the Royal New Zealand Foundation for the Blind, Techniques of Daily Living specialists and Retina New Zealand branches.

Will I have to give up sports and games?

Partially sighted and blind people participate in many sports and social activities. In fact, it is very important for all visually impaired people to make an effort to keep themselves fit and not to let their visual impairment become a reason for not fully participating.

Royal New Zealand Foundation for the Blind

More than 12000 New Zealanders are registered as members of the Foundation. Many of these people who lose their sight later in life, have some vision and require some type of rehabilitation service. The Foundation's rehabilitation services are designed to help those with a sight loss to obtain the skills they need to live independently in the community. The staff are specially trained and will provide services to members in their own home, at the local regional office or service centre.

The types of services offered are:

• Talking books or magazines from Library Services.
• Major daily newspapers read on the Telephone information Service.
• Counselling services.
• UV blocking sun glasses, magnifiers and other helpful equipment available from equipment services.
• Practical help in moving around your own community with Orientation and Mobility services.
• Useful tips on using household appliances safely, such as pouring hot drinks, available through Techniques of Daily Living Services.
• Help with finding employment through Vocational Services.
• Training in touch typing, use of Closed Circuit TV and computer equipment with Communication Services.
• Social contact with other members through the Foundation's Social Club.

For information about these and other Foundation services available in your region, ring Free phone 0800 24 33 33

Retina New Zealand

Retina New Zealand is a self-help group that seeks to assist its members to cope with their visual problems.

Local branches hold gatherings to socialise, provide peer support, exchange information and learn from guest speakers.

Retina New Zealand publishes a regular quarterly newsletter (in print, tape, e-mail or disk) which keeps members informed about the latest aids, up-to-date research into RD and other interesting facts for those with visual problems.

Our society is a full member of Retina International, which enables us to exchange information and research news with other member countries, and to keep our members right up to date on the progress of research into RD.

New members of Retina New Zealand are welcome. To join our society, please fill out the form at the end of this booklet. Membership is open to any person diagnosed with a retinal degenerative condition, their families and/or persons who do not have retinal degeneration but who are interested in furthering the aims and objects of the society.

All branches need more members and assistance in maintaining member contact, public awareness, office administration and so on. We all have a role to play and there is strength in unity. Please contact the branch nearest to you to offer your help in our "Fight for Sight".

Acknowledgements

Retina New Zealand wishes to acknowledge the contributions of the following people who have made this publication possible:

Members of the Otago/Southland Branch of the New Zealand RP Society and Dr Dianne Sharp who compiled the original version of this booklet;

Dr Marion Maw, chair of the Scientific and Medical Advisory Board who updated the original version of this booklet;

Dr Dianne Sharp and June Ombler for proofing and review;

The Scientific and Medical Advisory Board of Retina New Zealand for advice on content; and

The Foundation Fighting Blindness - Canada for design ideas.

Publication of this booklet was generously funded by the Royal New Zealand Foundation of the Blind. The Foundation also provides support services which complement the programmes of Retina New Zealand. The RNZFB has contracted with Retina New Zealand to provide its peer support and public education programmes.

Help the fight

There are many ways in which you can help Retina New Zealand to make a difference. Your membership of the society and/or involvement with gifts of time, energy, skills, enthusiasm, donations and bequests make a valuable contribution.