What is Ocular Amyloidosis?
Amyloidosis is an assortment of disorders recognized by the build-up of an abnormal protein known as amyloid in different body parts, including the eyes and structures surrounding them. This amyloid is a protein that becomes wrongly folded and insoluble. Then, it piles up in spaces within and outside cells in the body, causing an gradual damage to organs.
What Causes Ocular Amyloidosis?
Amyloidosis is a disease that can be either systemic, meaning it affects the whole body, or localized, affecting just one area. This condition can be primary, meaning it occurs on its own or secondary, arising due to uncontrollable inflammatory diseases.
Examples of such inflammatory diseases include chronic infections, autoimmune conditions (where the body’s immune system attacks its own cells), familial Mediterranean fever (an inherited inflammatory disorder), and plasma cell dyscrasia, such as multiple myeloma (types of cancer affecting a certain type of blood cells).
The categorization of the systemic disease depends on the type of amyloid protein that’s present. Medical professionals commonly refer to these as AL, meaning amyloid immunoglobulin light chain, AA, meaning amyloid A protein, or ATTR, meaning amyloid transport protein transthyretin.
Risk Factors and Frequency for Ocular Amyloidosis
AL amyloidosis, which is the most common type of systemic amyloidosis in the US, makes up about 78% of new cases each year. Meanwhile, the hereditary ATTR amyloidosis is not as common and is more common in men. On the other hand, AA amyloidosis, which can happen due to long-term inflammation, is quite rare.
Amyloidosis can also affect the eye with a high variety of symptoms. The most common type of ocular amyloidosis is usually due to localized AL amyloidosis. Roughly 12% of people with AL amyloidosis will have symptoms in the eye, and in 5% of the cases, such symptoms are the first sign of the disease.
- Most ocular symptoms in AL amyloidosis occur outside the eyeball affecting areas like the orbit, the conjunctiva, the temporal artery, and the muscles around the eye.
- In hereditary amyloidosis, like non-transthyretin familial amyloidosis, the cornea is primarily affected, accounting for 20% of the cases.
- In ATTR amyloidosis, 10% of the cases have vitreous involvement, but it rarely affects the retina.
- Secondary amyloidosis rarely leads to ocular symptoms.
- Ocular orbital amyloidosis typically occurs in people between 45 and 65 years old and affects both genders equally.
- In transthyretin amyloidosis, women have ocular symptoms more often than men; these represent 46% of the cases, compared to 15% in men.
Signs and Symptoms of Ocular Amyloidosis
Amyloidosis is a condition where the body deposits abnormal proteins, called amyloids, in organs and tissues. Depending on which part of the eye is affected, it can cause various kinds of symptoms. These include:
Orbital Amyloidosis
This form of amyloidosis usually affects the muscles and tissues around the eye (orbit). It can cause the eye to stick out more than usual (proptosis), limit eye movement, and even affect the optic nerve. It may also cause a swollen mass in the upper part of the eye socket if it involves the lacrimal gland (which produces tears). Sometimes, amyloidosis can lead to discoloration around the eyelids and surrounding areas.
Conjunctival Amyloidosis
This affects the conjunctiva, which is the clear tissue covering the white part of the eye and the inside of the eyelids. It can cause nodules, or bumps, on the bulbar or tarsal conjunctiva, resulting in drooping of the upper eyelid (ptosis) or discomfort and visual problems. In some cases, it can also lead to bleeding under the conjunctiva.
Corneal Amyloidosis
In this form, amyloid deposits occur in the cornea (the clear front surface of the eye). It can cause either gelatinous drop-like corneal dystrophy (a rare condition that results in discomfort and vision problems) or lattice corneal dystrophy (a condition that results in lines, or lattice-like patterns, in the cornea leading to vision loss).
Vitreoretinal Amyloidosis
This rare form affects the vitreous (the jelly-like substance in the back of the eye) and retina (the light-sensitive layer at the back of the eye). It can cause vitreous opacities, which are abnormal growths in the vitreous humor that can cause various visual symptoms. In some cases, there might be retinal hemorrhages and cotton wool spots, increasing the rate of retinal vein occlusions.
In any form of ocular amyloidosis, an early and accurate diagnosis is crucial to prevent further complications and progression of the disease.
Testing for Ocular Amyloidosis
If your doctor suspects you might have a condition called ocular amyloidosis, they can confirm this by taking a small sample of the affected area (a biopsy) and further examining it under a microscope. Samples can be taken from various areas including from the thin, transparent skin layer covering the front of your eye (the conjunctiva), eyelids, tear glands, or the artery on the side of your head (the temporal artery). Sometimes, your doctor might need to collect samples from the thick, jelly-like substance filling the space between the lens and the retina in your eye (the vitreous). If you have a growth or lump (a mass) near your eye, your doctor might need to collect a sample from this area to confirm the diagnosis and rule out any other conditions.
Your doctor might also want to take some images of your eye using computed tomography (CT) scans or magnetic resonance imaging (MRI). CT scans can provide more detailed information in cases of ocular amyloidosis as they are better at detecting changes in your bone and in the mineral content of your tissues. If you have a mass, it may cause parts of your eye to move out of place. You may also see changes in the muscles that control eye movement, an increase in the soft tissue, or even mineral deposits. However, MRIs can give a clear picture of the exact extent of the growth or lump.
If your amyloidosis affects the layers at the back of your eye, your doctor may perform a test called fundus fluorescein angiography. This test uses a special dye to visualize the blood vessels in the back of the eye and might show blockages or leakages. They might also use a technique called Optical Coherence Tomography which can show deposits that look like needles on the surface of your retina extending to the vitreous cavity.
If you have been diagnosed with amyloidosis in one part of your body, it’s a good idea to check other parts too, as this disease can sometimes affect more than one site. Your doctor might suggest taking bite-sized samples from fat under your skin or bone marrow for further testing. They might also perform a series of other tests such as a complete blood count, urine test, liver and kidney function tests, chest x-ray, electrocardiogram (which looks at the electrical activity of your heart), echocardiography (ultrasound of the heart), and an ultrasound of your abdomen.
Treatment Options for Ocular Amyloidosis
Upon identifying a patient with the disease, it’s important to check whether other parts of the body are affected. For those with localized amyloidosis who don’t show severe symptoms, doctors often recommend a ‘watch and wait’ approach. If the disease has spread significantly in the conjunctiva (the clear tissue covering the front of the eye), regular check-ups are crucial, as methods like surgical removal are not very effective.
Surgery to remove large amounts of the disease tissue may benefit those who are experiencing noticeable symptoms such as eye movement problems, pressure on the optic nerve (the nerve that connects the eye to the brain), or cosmetic concerns. But for patients who can’t undergo surgery due to other health issues, or those with widespread disease, radiotherapy with or without surgical removal could be helpful. It’s essential to keep a close eye on these patients to avoid any complications.
Cryotherapy, a treatment using extreme cold, might also work well for conjunctival amyloidosis, as it can cut off the blood supply to the amyloid deposits, causing them to shrink. It may be beneficial to perform surgery before cryotherapy to allow better access to freeze the deeper blood supply.
What else can Ocular Amyloidosis be?
Problems with the lacrimal glands, which produce tears, can seem like other conditions like lymph growth disorders, abnormal blood vessels, inflammation of the gland, or even tumors in the gland. Doctors often use a CT scan to check for bone damage or calcification. However, the final diagnosis is made by taking a tissue sample for closer examination under a microscope. Some conditions that can look like orbital amyloidosis, a particular type of eye problem, include a false tumor, lymph problems, sarcoidosis, or a blood-filled swelling in the eye. Specific signs found in CT scans and MRI scans can help distinguish these conditions.
Certain glassy deposits in the cornea of the eye (corneal amyloidosis) can also be confused with other forms of genetic eye disorders (corneal dystrophies). Other conditions to rule out include disorders due to abnormal proteins in the blood, cholesterol transport problems, rare genetic conditions like Fabry disease or cystinosis, metabolic problems causing the buildup of certain substances in the body (like mucopolysaccharides, lipids, or mucolipids), and skin conditions like X-linked ichthyosis or keratosis follicularis. For deposits in the jelly-like substance and retina of the eye (vitreoretinal amyloidosis), the main conditions to consider are inflammation of the middle layer of the eye due to infection or other causes, disguises like eye lymphoma, and multiple sclerosis. After considering various causes for inflammation within the eye, examining the removed jelly-like substance under the microscope helps confirm the diagnosis.
What to expect with Ocular Amyloidosis
Orbital amyloidosis is a condition which affects your eye area. How severe this disease gets and how it may impact you relies on how wide-spread it is and where specifically it takes place. If you’re not showing any symptoms, doctors may just keep an eye on it. However, if symptoms do occur, surgical removal of the disease-affected mass could be necessary. “Cryotherapy”, a cold treatment, is used to further deal with any remaining harmful tissue. However, the disease may come back often if all the affected tissues in the conjunctival, the clear tissue covering the white part of the eye, are not removed.
In some cases, the muscle that helps lift your eyelid might need to be removed but this situation is quite rare. External beam radiotherapy, a type of cancer treatment, could help patients if the disease is likely to come back even after surgical removal.
Corneal dystrophy type I and type III are conditions of the cornea – the clear front surface of the eye. Type I starts to show visual symptoms by 10 years of age, and vision may get highly affected by the age of 40 to 60. Type III usually starts to impact vision after 40 years of age, and gets worse post 60. In both types, the disease is progressive and there are no known treatments to prevent the vision impairment.
Doctors usually treat eye cloudiness, or corneal opacities, with “deep anterior lamellar keratoplasty”, a type of surgery. However, the disease could come back and the body could reject the new tissue. Another treatment avenue is a “penetrating keratoplasty”, a slightly different type of surgery. There have been cases where all transplanted tissues have survived for 12 years post-surgery.
For patients with Meretoja syndrome, a hereditary systemic disorder that causes abnormal accumulation of protein deposits in organs, there is no curative treatment available. Visual symptoms often appear before 25 years of age, but most people can still see quite well up to 65 years of age. Treating dry eyes early can help manage symptoms. Another method of treatment in cases where repeat corneal ulcers and corneal scarring cause cloudiness of the cornea is keratoplasty. However, the visual outcome after this type of procedure is generally poor due to certain complications such as dry eye, persistent epithelial defects, and the continuous deposition of amyloid (abnormal protein) in the transplanted cornea.
In gelatinous drop-like corneal dystrophy, a rare eye disorder that leads to vision loss, visual symptoms usually occur before the age of 10, with significant visual impairment by the age of 10 to 30. Eye surgeries like penetrating keratoplasty, deep lamellar keratoplasty, or superficial keratectomy can help restore good vision, but the disease could come back soon after the surgery.
In the case of vitreoretinal amyloidosis, a “pars plana vitrectomy”, an eye procedure, usually reduces the blur or haze in vision and significantly improves visual clarity. However, the disease may come back in about 25% of patients due to either residual vitreous behind the lens, the constant production of amyloid fibrils (misfolded proteins) by cells in the retina, or both. In these specific cases, repeated vitrectomy could be necessary.
Possible Complications When Diagnosed with Ocular Amyloidosis
The different complications of an eye condition vary based on which part of the eye is affected. Here’s a look at some possible complications:
- Amyloidosis affecting the orbital or ocular adnexal (the surrounding tissue of the eye).
- Ptosis (dropping eyelids), eyelid swelling, proptosis (bulging eyes), lid or conjunctival masses, ophthalmoplegia (eye muscle weakness), and paresis of accommodation (difficulty focusing).
- Amyloid proteins collecting in the trabecular meshwork (drainage canals in the eye) that can lead to glaucoma.
- Corneal amyloidosis (a disorder that causes deposits to form in the cornea).
- Keratoconjunctivitis sicca (dry eye), opacification of the cornea (clouding or scarring of the cornea), and severe visual loss.
- Vitreoretinal disorders (diseases affecting the retina and vitreous humour).
- ATTR amyloidosis, which can cause significant visual defects due to dense vitreous opacities (cloudiness in the vitreous humour – the clear gel that fills the space between the lens and the retina of the eye).
Preventing Ocular Amyloidosis
If you’ve been diagnosed with ocular amyloidosis, which is a rare condition where abnormal proteins build up in your eyes, it’s critical to understand that this disease can have effects on other parts of your body too. It’s important to also meet and discuss your condition with an internist, a doctor who specializes in internal medicine and can treat diseases affecting various organs in your body. Further, you may need to see other types of doctors depending on your symptoms and health situation. One key point to remember is the necessity of regular check-ups. These ongoing appointments with both your general doctor and your eye specialist (ophthalmologist) are vital. They help to monitor your condition, adjust treatment if needed, and manage any potential complications effectively.
