Preventing Blindness: The Stepladder Approach
Why The Step Ladder Approach?
The goal of our mission is to ensure no one goes blind from ocular inflammatory disease in this day and age. Ocular Inflammatory Disease (OID) including uveitis, represents the third leading cause of preventable blindness in the developed world, accounting for up to 10% of all severe vision impairment cases.
The Ocular Immunology and Uveitis Foundation (OIUF), founded by world-renowned ocular immunologist, Dr. C. Stephen Foster, was at the global forefront of this battle. Dr. Foster spent 20 of his 50-year career working tirelessly to find a cure for OID and he did by studying the immune system and developing the Step Ladder Approach to care.
About The Step Ladder Approach
Dr. Foster discovered in OID that if one can suppress the immune system from attacking itself with immunomodulatory medications and not steroids, the immune system would regulate its memory and forget that its cells were enemy cells therefore stop attacking them. The objective of modern ocular immunology in treating noninfectious OID is to achieve complete, steroid-free disease remission before permanent structural damage occurs to preserve vision for the future.
The ultimate goal of therapy is total remission or cure of the ocular inflammatory disease off all medication. The road to remission can be bumpy, as some forms of ocular inflammatory disease can be very aggressive and “stubborn” to control, but one needs to remember Dr Foster’s philosophy of care and that is “To Never Give Up” and “Do Whatever it Takes” for the “mission of remission”. The treatment of OID is aimed at the cause when it is identifiable.
The Step Ladder Approach to treating OID:
In the step ladder approach for non-infectious causes of inflammation, including idiopathic causes, ophthalmologists specializing in ocular immunology will utilize the step ladder approach algorithm to systematically modify the immune system while protecting overall patient health. The provider may even combine medications from different steps to control inflammation if necessary. If it is infectious, your provider will prescribe antibiotics or antivirals, etc. pending the infectious cause.
The importance of this approach cannot be overstated. The purpose is not merely to make you feel better during a flare by suppressing acute inflammation nor managing episodic flare-ups. It is to stop the inflammatory process before repeated or persistent inflammation or chronic steroid use causes irreversible injury and permanent loss of vision. Remember, low-grade inflammation acts as a silent destroyer inside the eye, accumulating micro-damage over time in addition to chronic steroid use.
Steps to Care
- Role: Front-line rescue therapy administered topically (drops), locally (periocular or intravitreal injections/implants), orally, or via intravenous(IV) infusion. The form of steroid that is prescribed depends on the severity and type of OID one has.
- Objective: Steroid is an effective medication in quickly aborting acute inflammation to prevent vision robbing complications, but used long-term, it results in its own set of complications, such as, cataracts, high eye pressure resulting in glaucoma, stomach ulcer, osteoporosis (bone thinning), diabetes, cardiovascular disease, weight gain, fluid retention, and Cushing’s syndrome.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDS) may be used.
- Role: Systemic oral NSAIDs (e.g., Naproxen, Celecoxib, Indomethacin) used as an NSAIDS are a nonsteroidal type of medication aimed at suppressing inflammation in
certain types of OID. - Monitoring: Oral NSAIDS require monitoring of your liver and kidney function.Certain types of oral NSAIDS, if used long-term, will need added medication for
protection against stomach ulcers and blood pressure evaluations.
- Role: This first-line steroid-sparing systemic therapy is applied when inflammation recurs with steroid tapering or failure with NSAID therapy. The use of such medication requires special, regular monitoring (blood tests) to ensure that no hidden side effects are creeping in.
- Goal: suppress immune system leading to remission and cure. Examples of conventional IMT include Methotrexate, Cellcept or Mycophenolate, Imuran or
Azathioprine, Cyclophosphamide, Leukeran or Chlorambucil, and Cyclosporine.
Your provider will always start with the type that he or she believes is most appropriate for you and your type of OID. In addition, the medication which has the least potential for side effects is favored. In some cases, you may need a combination of two or more medications as well.
- Safety: A good safety profile when monitored and administered at lower immunomodulatory dosages compared to oncologic regimens. Regrettably, many people (including a surprising number of healthcare providers) are unaware of the very favorable risk-to-benefit ratio of such medications used in the doses that
rheumatologists, ocular immunologists, and other specialists prescribe for immunomodulation of autoimmune disease. As a result, many people equate the use of such medicine with the high doses given in oncology, with all the risks and side effects that occur at these high doses. This is not at all what IMT for OID is all about. Used correctly by a provider who is an expert in such matters, the patient with OID who is treated with IMT should look and feel normal. If an IMT medication disagrees with you, that medication should be stopped, and another tried, so that the goal of no inflammation on no corticosteroids and no significant IMT side effects is achieved. - This misunderstanding can have serious consequences when it leads to inadequate treatment of a disease that threatens vision. The purpose of IMT is to control the immune system’s attack on the eye and prevent inflammation from continuing to cause damage. For patients whose disease cannot be adequately controlled with simpler treatments, avoiding appropriate immunomodulatory treatment can mean allowing inflammation to continue—and continued inflammation can ultimately result in permanent vision loss.
Role: A newer category of IMT employed for the treatment of autoimmune diseases called biologic response modifiers (BRM) or biologics exists. The BRMs more specifically target certain elements of the immune system and, in so doing, avoid some of the potential risks of the more conventional IMT medications. In some cases you may be on a conventional IMT with a BRM for best control of inflammation.
- BRMs can be self-injectable or administered intravenously. There are many on the
market but clinical research for efficacy in OID has mainly been done on brand names: Remicade, Humira, Actemra, Acthar, Rituxan, and Tepezza for thyroid eye disease(TED). Biosimilars of these brand names exist except Tepezza, but remember these molecules are similar and not identical to their name brand. Many Humira biosimilars have good efficacy, such as Hadlima or Simlandi, but we have not found the same with
other BRM brand name biosimilars.
There are other IMT regimens that may be trialedsuch as intravenous Immunoglobulin G (IVIG). IVIG not only modulates the immune modulates but it also helps fight infection. This can be added to a current therapy or used as a stand-alone, but it is last on the ladder because of the tedious nature of the infusion being 3 days every month and the cost. Sometimes, a long-acting steroid implant in the eye is necessary in stubborn cases and again may be added to an IMT regimen.
Expected Duration of Treatment
The duration of treatment varies person to person and depends on the type and cause of ocular inflammatory disease. Simple forms of uveitis, for example, may respond to treatment within days and may not recur.
- Chronic (long-term, recurring) forms of ocular inflammatory disease that threaten vision can be very difficult to cure and require persistence on the part of the treating physician(s) and patient. When a disease threatens vision, the stakes are extraordinarily high: the purpose of sustained treatment is to prevent inflammation from causing irreversible damage before it is too late.
- The length of time required to get the disease into a durable remission on IMT is difficult to quantify and is very individualistic, but a minimum of two years is a reasonable estimate. During treatment on IMT, one can expect visits to the ophthalmologist every 4-6 weeks approximately with lab monitoring.
- With appropriate, targeted treatment, most people with ocular inflammatory disease will become well-controlled and progress to remission. Once in remission from ocular inflammatory disease, you should expect to have regular follow-up visits to your provider to make sure that the disease remains in remission resulting in cure.