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UVEITIS CORNER: Looking Back and Forward at Uveitis

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In this inaugural “Uveitis Corner” column, Sunil Srivastava, MD, of Cole Eye Institute at Cleveland Clinic, invites Glenn Jaffe, MD, and David Callanan, MD, to discuss the evolution of uveitis therapy within the retinal specialist community. Dr. Jaffe is the Robert Machemer, MD Professor of Ophthalmology and chief of the retina service at Duke University. Dr. Callanan is a vitreoretinal surgeon and uveitis expert with Texas Retina Associates.

Dr. Srivastava: Dr. Callanan and Dr. Jaffe, both of you are prominent vitreoretinal surgeons and uveitis specialists. What was the attraction for you to train in both? How has the interest in uveitis helped you with your vitreoretinal patients, and how has the interest in vitreoretinal diseases helped in managing your uveitis patients?

Dr. Callanan: I was attracted to both retina and uveitis because it seemed that each case was unique. It seems that each patient’s eye has characteristics that make it different, so the surgical approach must be tailored for each patient. Vitreoretinal training always helped me feel more comfortable when considering diagnostic vitrectomy to make the correct diagnosis in posterior uveitis. Similarly, uveitis training always reminded me to look for underlying causes of retinal pathology. Every vitreoretinal specialist inevitably sees some posterior uveitis cases, and having extra training helps in diagnosing and managing these. Uveitis cases are certainly some of the most intellectually challenging, and vitreoretinal cases are some of the most surgically challenging. Who ever said life was going to be easy?

Dr. Jaffe: I first became interested in uveitis and retina as a resident at UC San Francisco. In those days, although uveitis faculty were primarily oriented toward the anterior segment, the retina faculty interacted with the uveitis faculty and I saw that it might be possible to combine both specialties in a career. After my vitreoretinal fellowship, I was hired by Robert Machemer, MD, to join the vitreoretinal faculty at Duke University. At that time, there were no uveitis specialists in the area. I felt that I could establish a niche as a vitreoretinal specialist who managed complex uveitis cases. This combination established a satisfying career in which I have applied my vitreoretinal training to treat patients with complex uveitis, particularly those with intermediate, posterior, and panuveitis.

Vitreoretinal specialists have a unique perspective on patients with uveitis. They can surgically treat uveitic-associated posterior-segment complications such as epiretinal membrane, macular hole, RD, and vitreous opacity. They can implant long-acting, sustained drug-delivery systems and can help to establish the underlying uveitic diagnosis with a diagnostic vitrectomy. Vitreoretinal specialists are also very accustomed to giving intravitreal injections, and local injection therapy is an important component of uveitis management.

I also believe that my care of uveitis patients has helped in my management of nonuveitic patients with associated systemic disease. For example, it has made me pay more attention to underlying systemic conditions, such as cardiovascular disease and hypertension, that can exacerbate retinal diseases like DR and vein occlusion.

Dr. Srivastava: As retina specialists increasingly treat uveitis patients, what are some things that they should be careful of in their management of these complex cases?

Dr. Callanan: One of the greatest potential pitfalls for the busy retinal surgeon is injecting intravitreal steroids in an eye with uveitis that is infectious in etiology. Most surgeons quickly adopted the use of intravitreal triamcinolone over the last decade. It quickly controls noninfectious uveitis, but is the worst possible thing to do if the uveitis is viral in nature, like acute retinal necrosis. Toxoplasmosis and fungal infections can rapidly get worse if undiagnosed and treated with steroid before appropriate antibiotics are started. Always try to confirm your diagnosis, and if unsure, consider a vitreous biopsy. The other common mistake is to treat chronic uveitis conditions only when they flare up, allowing cumulative damage over time while the patient suffers repetitive recurrences.

Dr. Jaffe: Many patients with uveitis who have been referred to me by vitreoretinal specialists have inflammation that is not controlled. For example, I have seen several patients who were given anti-VEGF therapy to treat uveitic macular edema, without success. In these patients, the underlying inflammation needs to be treated, either with corticosteroids or immunomodulating agents, to achieve a durable effect on the macular edema. I would also caution the vitreoretinal surgeon to maximize anti-inflammatory therapy when he or she undertakes vitreoretinal therapy in an eye with uveitis. In particular, hypotony can result if anterior-segment inflammation is not controlled before scleral incisions are made, and it is often beneficial to give a periocular or intravitreal steroid injection at the conclusion of surgery to minimize postoperative inflammation.

Dr. Srivastava: How do you manage systemic immune suppression? Do you prescribe it on your own? Is there an advantage or disadvantage to how you handle systemic immune suppression? Do you see more retina specialists prescribing drugs like Humira?

Dr. Callanan: Adalimumab (Humira; AbbVie Inc.) is one of the easier systemic agents to prescribe for uveitis patients. Tuberculosis needs to be ruled out at the beginning and I usually check for hepatitis exposure. Once this is done, there is minimal laboratory follow-up, unlike with methotrexate and mycophenolate. For this reason, I think there will be a few more retinal specialists that will directly prescribe and monitor this medication, but I suspect most retina specialists will not do this on their own. I encourage retina specialists to develop a good relationship with local rheumatologists who can help manage systemic medications.

Dr. Jaffe: When I first arrived at Duke, I was fortunate that a Duke rheumatologist had a significant interest in patients with uveitis, and agreed to attend my uveitis clinic. I partner with a rheumatologist, Robert Keenan, MD, who attends the uveitis clinic and manages systemic aspects of the patient’s evaluation and treatment. Dr. Keenan has a separate patient schedule so that he can bill independently. However, we collaborate on the immunosuppressive care of our jointly managed patients. This model has worked extremely well. It ensures optimal communication with the rheumatologist, since we can speak directly to one another when the patient is in clinic. We have learned from each other, so that when he is out of town I am better able to manage the immunosuppression on our patients, and when I describe the patient’s history and examination, he completely understands the terminology, and he can appropriately manage the patient’s immunosuppression. It has been fun to bounce ideas off one another. I believe this interaction has resulted in a high level of patient care, but has also been a great teaching opportunity for me, the residents, and the fellows, who see patients in the uveitis clinic. In addition, I have separated my clinics so that I see patients with uveitis on one day and patients with general medical and surgical vitreoretinal diseases on another day, which further facilitates patient flow.

Humira (recently approved to treat intermediate, posterior, and panuveitis) and another TNF inhibitor, infliximab (Remicade; Janssen Biotech), can be very effective, and increasingly, vitreoretinal specialists are using this treatment to treat their patients with uveitis. However, there are caveats. In cases of intermediate uveitis, where there is an underlying predisposition to demyelinating disease such as multiple sclerosis, it is important to obtain a brain MRI to rule out underlying demyelination, which would contraindicate treatment with a TNF inhibitor such as adalimumab. In addition, immunomodulating agents, such as the TNF inhibitors, can exacerbate underlying infections, and it is important to rule out conditions such as tuberculosis before initiating therapy.

Dr. Srivastava: You both have been instrumental advocates in the development and approval of chronic local therapy for uveitis. Which local therapy on the horizon is the most intriguing to you?

Dr. Callanan: I think we will hopefully have injectable sustained-release steroids. Either the suprachoroidal administration, such as the approach from Clearside, or posterior-chamber implants from pSivida that could last up to 6 or 12 months with far fewer IOP effects. Steroids still have the broadest range of action and rapid onset.

Dr. Jaffe: The surgically implanted fluocinolone acetonide sustained-delivery implant, Retisert (Bausch + Lomb), very effectively controls inflammation, and may minimize or eliminate the need for adjunctive therapy. However, this implant has associated side effects of elevated IOP and requires surgical placement in the operating room.

Over the past few years, we have been working on an injectable form of the fluocinolone acetonide implant, similar to Iluvien, used to treat chronic diabetic macular edema. This system has the significant advantage of an office-based procedure to place the implant that provides 2- to 3-year drug delivery, and appears to have a lower rate of steroid-induced increased IOP when compared to the surgically placed implant. The technique to place the implant in the office is straightforward, and is similar to placing small-gauge cannulas during vitreoretinal surgery. So far, the results of this treatment approach have been very favorable, and patients have appreciated a procedure that does not require a trip to the operating room. Hopefully, this implant will become available for general use in the not-too-distant future.

Dr. Srivastava: Finally, what’s your opinion of the future of uveitis management by retina specialists? Is there anything that excites you or worries you?

Dr. Callanan: I feel that the average vitreoretinal fellow is now more frequently exposed to uveitis specialists in their training. This will give them more confidence in treating uveitis cases especially as our treatment options expand. There are also more uveitis specialists available to give consultation on difficult cases. It should be easier to treat the chronic noninfectious cases as we get access to medications that reliably control the inflammation with fewer side effects. Vitreoretinal specialists were not comfortable prescribing systemic medications that they were unfamiliar with. Increased local options will help alleviate some of this reluctance. There will always be a need for interaction with rheumatologists to assist in managing uveitis cases associated with systemic disease. It seems that the approval of Humira for uveitis has increased the interaction between the two specialties.

Dr. Jaffe: The future is bright for uveitis management by vitreoretinal specialists. Although these patients often have complex ocular and systemic problems, they are among the most interesting in my practice. In addition to novel drug delivery systems, the range of drugs that we will have to treat these patients is expanding. Pharmaceutical companies have taken an interest in the uveitis space. There are several ongoing and planned new trials of local and systemic therapy. I believe that vitreoretinal specialists will be well positioned to take advantage of these new treatments as they become available. RP