Women at greater risk for autoimmune diseases with ocular manifestations

  episcleritis

Communication with physicians managing the patient’s systemic disease is crucial.

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“There is a danger dose, which is measured in milligrams per kilogram, so a smaller person would be more likely to be at that danger dose using a regular dose of Plaquenil,” Dr. Colby said. “It causes a retinopathy, basically dysfunction of the retina cells.”

The site for some of the most serious ocular complications of lupus is the retina, Dr. Foster said.

“Patients with lupus can develop an immune complex vasculitis with the lodging of immune complexes forming in the vasculature, both in the choroid and in the retinal vasculature itself,” he explained.

This ophthalmic emergency can cause permanent vision loss, but it can also be a prompt for systemic lupus testing in an as yet undiagnosed patient or a sign of similar immune complexes in other areas of the body.

“Ophthalmologists have a spectacular opportunity not only to influence the situation but also to be lifesavers as well if they make the diagnosis of lupus in the patient,” Dr. Foster said. “The presence of lupus retinopathy with retinal vasculitis or choroidopathy is a terrifically reliable hallmark of the presence of these immune complexes lodging in other areas as well, most particularly the brain and the kidney. The likelihood of the patient dying from one of those sites being affected by lupus nephropathy or lupus affecting the central nervous system is very high in the patient with lupus retinopathy who is not properly, appropriately and aggressively treated.”

Rheumatoid arthritis

Rheumatoid arthritis, another collagen vascular disease, is four times more common in women than men and presents problems similar to those with lupus, including dry eye.

“You can also get scleritis and pretty severe inflammatory disorders, things like melting of the peripheral cornea,” Dr. Colby said. “There’s a lot of overlap with lupus.”

Dr. Foster said the approach to treating dry eye or secondary Sjögren’s in rheumatoid arthritis patients is much like that in lupus, including the use of Restasis (cyclosporine ophthalmic emulsion, Allergan) along with heat and massage to improve the function of the meibomian glands.

In addition, he said, the ophthalmologist must be aware of the patient’s systemic disease management to best treat its ocular manifestations.

“See if there is any evidence of the underlying rheumatoid disease being active, so to speak, even if it’s not active in the joints,” Dr. Foster said. “Are there markers in the blood that would indicate that chronic low-grade inflammatory activity is afoot? If so, deal with that systemically with a sprucing up of the systemic medication program.”

Dr. Foster said that scleritis and peripheral keratitis are all “absolutely dreadful” ocular manifestations of rheumatoid disease that require systemic therapy, often aggressive.

Dr. Colby added, “The important thing with the systemic diseases is, the better the systemic diseases are managed, the easier it is to manage the ophthalmic manifestations. I can treat someone’s rheumatoid-associated dry eye all I want, but if their systemic rheumatoid disease is not under control it’s like sticking your finger in the dike.”

Scleroderma

Three times as many women as men experience scleroderma, or progressive systemic sclerosis, a connective tissue disease.

C. Stephen Foster

“Scleroderma is a very different beast from lupus and rheumatoid disease, with less known about it and less discovered thus far in terms of a routinely highly effective therapy,” Dr. Foster said. “Breakthroughs are being made, and there are increasing levels of optimism among the medical community with respect to being able to prevail over some of the more relentless manifestations of scleroderma.”

Patients with scleroderma are likely to develop dry eye, which is treated as in other autoimmune diseases. The condition also causes shrinkage of areas of the skin, including the conjunctiva, Dr. Foster said.

“Patients sometimes develop shrinkage of the conjunctiva with a shortening of the inferior fornix,” he said. “It probably has to do with laying down new collagen, perhaps type 3 collagen or embryonic collagen. This contracts and you get shrinkage.”

Choroidopathy and vascular occlusion can also occur.

“Just as in lupus, this is a wake-up call that the patient’s scleroderma has taken a nasty turn,” Dr. Foster said.

Unfortunately, he said, there is no treatment for conjunctival shrinkage, and clinical trials for treatment of vascular occlusions are “maddeningly difficult” because of the small number of patients in any one center.

“One could speculate that the same approach that has been employed in the scleroderma lung research, namely with high dose cyclophosphamide therapy intravenously and other kinds of aggressive immunosuppressive therapy, might be beneficial in patients who are developing the scleroderma choroidopathy, but frankly it’s not known,” Dr. Foster said.

Hyperthyroiditis

Hyperthyroiditis affects women seven times as often as men. Its main ocular manifestation is Graves’ orbitopathy.

“That often is relatively mild and basically cosmetic,” Dr. Foster said, “but it is graded and assigned different grades, with severity and vision threat being greater the higher the grade of the thyroid eye disease is.”

Dr. Colby explained that in Graves’ orbitopathy infiltration of inflammatory cells within the extraocular muscles causes proptosis.

“You can have exposure of the cornea, which can lead to corneal ulcers. More seriously, if the muscles are very infiltrated, “crowding” of the orbit can compress the optic nerve of the eye, which can cause vision loss,” she said. “Graves’ disease can also cause double vision because if the muscles are very infiltrated they don’t move properly.”

Mild exposure can be treated with ointment or taping of the lids, Dr. Colby said. More advanced disease may require partial tarsorrhaphy. In extreme cases, orbital decompression surgery may be called for.

Dr. Foster said, “As the space occupied by the infiltrating cells, the proliferating fibroblasts, steadily increases, there is only so much space in the orbit, and the optic nerves can get increasingly compressed. That’s something that is typically tackled surgically with decompression surgery.”

Working with other physicians

Given that ocular manifestations of autoimmune disease are related to the status of the systemic disease, Drs. Foster and Colby said ophthalmologists must maintain relationships with the patient’s ocular immunologist or rheumatologist during treatment.

“With any of those diseases, the systemic management is really key,” Dr. Colby said. “Often if the eye is out of control, it means the body is out of control, even if the patient is not having systemic symptoms.”

She suggested that ophthalmologists make sure to speak clearly with collaborating physicians, using terms that the other specialist will understand.

“It’s important to really be convinced of the concept that appropriate systemic management will only make the ophthalmologist’s life easier and make it easier to manage patients’ problems,” Dr. Colby said.

“Communication is critical,” Dr. Foster agreed.

He said good communication will come into play when the eye reveals deeper problems in the body. If this is the case, it is the responsibility of the ophthalmologist to demonstrate that to the rheumatologist and to ensure that the patient receives proper systemic care.

“The patient, from a rheumatologist’s standpoint, may still be in remission,” Dr. Foster said. “The ophthalmologist is duty-bound, in my judgment, to convince that rheumatologist that this is not so – that the eye, although it may seem trivial, is extremely important and is telling you, ‘Wake up, pay attention, increase the aggressive therapy.’ If you don’t, you’re going to be sorry 6 months from now because the kidney or the lung is going to be in trouble.”

• Janine A. Smith, MD, can be reached at the National Eye Institute 31 Center Drive, MSC 2510, Bethesda, MD, 20892; 301-496-9058; fax: 301-496-2297.
• Kathryn Colby, MD, PhD, can be reached at the Massachusetts Eye and Ear Infirmary, 243 Charles St., Suite 808, Boston, MA 02114; 617-573-5537; fax: 617-573-3364. Dr.
• C. Stephen Foster, MD, can be reached at Ocular Immunology and Uveitis Foundation, Massachusetts Eye Research Surgery Institute, 5 Cambridge Center, Eighth Floor, Cambridge, MA 02142; 617-742-6377; fax: 617-227-1185.