Retina specialists often can’t control what walks through the clinic doors, and uveitis management, while gratifying, brings its own set of challenges. In this column, the new “Uveitis Corner” editor, Sruthi Arepalli, MD, interviews 3 vitreoretinal and uveitis physicians on their management of patients.

Sruthi Arepalli, MD: Thank you to all of you for taking the time to be here for our readership. I think one of the most intimidating things about uveitis management is the fear of missing a serious condition. What pearls would you offer to retina specialists who don’t see uveitis often, especially when they’re concerned that they’re leaving an important infectious or a potentially blinding etiology off their differential?

Ramana Moorthy, MD: A thorough history and review of systems and current medications are important first steps. Knowing not only the detailed ocular history but also the systemic conditions for which the patient is being treated can provide great clues as to the underlying cause of the uveitis. The patient might even be on medications (like bisphosphonates) that could induce uveitis.

Steven Yeh, MD: An examination of the anatomic structures involved can really drive our differential diagnosis. I’m also always thinking about the possibility of something infectious and what diagnostic tools I would need for that. Syphilis is on the rise in prevalence. If there’s a retinitis, you always want to think about herpetic retinitis. Also, looking for subtle signs like transillumination defects or ocular hypertension in the context of anterior uveitis can help you avoid corticosteroids that can be detrimental.

Phoebe Lin, MD: I would add that it’s important to refer early, especially with pediatric uveitis.

SA: We often are referred uveitis cases for surgical management. These cases are exciting and challenging. What would advice would you give to a retina specialist who will be operating on a patient with uveitis?

RM: If a patient who had uveitis developed a retinal detachment (RD), the approach would be based on the level of control of the uveitis prior to the planned surgical intervention. In a macula-on RD, the case might be more urgent and treatment of the RD may take precedence, but, if possible, try to get the inflammation as well controlled as possible prior to and after the surgery. In cases of elective posterior segment surgery or if RD surgery can be delayed safely, I would try to get the inflammation as well controlled as possible for at least 3 months prior. If it’s mainly anterior uveitis and I’ve been able to control it with topical medications, I would increase the frequency of the topical drops to hourly starting about a week prior to surgery, and then gradually taper. If patients have historically required more than topical agents to control their uveitis, I typically will pulse them with oral prednisone, if there are no contraindications, 40 mg a day starting a week before and gradually tapering for 4 to 6 weeks following the surgery.

I’ve also seen patients with chronic RD who have uveitis. The uveitis may indeed be related to the chronic retinal detachment. In those cases, fixing the RD solves the uveitis problem.

PL: One caveat in anterior uveitis is that B27 uveitis can be very deceptive because although it can be quiet for months, the postoperative response can be quite robust. I’ve had patients go into an inappropriate refractory hypotony with uveitic cystoid macular edema (CME) after routine cataract surgery even when they actually received very good perioperative control with steroids. In those cases, I actually increase the perioperative treatment in comparison to other anterior uveitis cases. Patients with juvenile idiopathic arthritis uveitis or tubulointerstitial nephritis and uveitis are already on immunosuppression, so perhaps that is what makes them less susceptible.

SY: I have given intravitreal dexamethasone (Ozurdex; Allergan) in the perioperative period for individuals who are predisposed to CME. I haven’t given suprachoroidal triamcinolone acetonide (Xipere; Bausch + Lomb), but it does stand to reason that would be a consideration.

SA: What advice would you give to your younger self when tackling difficult uveitic or retina patients, especially to avoid burnout?

RM: It’s nice to be able to bounce tough cases off partners, and the Uveitis Discussion Group (a discussion forum available only to members of the American Uveitis Society [AUS]) is an invaluable resource. You can ask 200 amazing uveitis experts about specific cases if you don’t know how to manage them. Those 2 things can help prevent you from feeling alone, which can happen in private practice. Twenty-seven years ago, I didn’t have adalimumab (Humira; Abbvie) or even mycophenolate mofetil (Cellcept; Genentech). I managed my own immunosuppressive therapy, but I was also fortunate that the pediatric rheumatologists at our children’s hospital were very good and could help me with pediatric uveitis cases. It was great to have that backup because the pediatric cases are very challenging.

For adult patients, if you are managing immunosuppressive therapy and you feel comfortable doing that, you really need to have a way to monitor blood tests, especially in private practice. I have a system that I’ve set up over the last couple of decades where a team of people keeps track of all of the blood tests for patients we have currently on immunosuppressive therapy. We manage a table that has patient names, meds, and frequency of blood testing. In the academic environment, I can typically enlist the help of residents, but in private practice I have really needed the support of a team of several people.

SY: I’ve had a medical assistant who helps to keep track of labs. You end up developing and refining your own system over time, and it can vary by practice.

PL: I would recommend reaching out to your potential infectious disease specialist and rheumatologist partners ahead of time, not waiting for that zebra case. Establish a relationship with them and give talks at their departments to start that collaboration, so that you have a network when a mystery case comes in.

Something that I’d like to see is an organization creating some guidelines on the information that the patient needs in terms of counseling around immunosuppression. There are new aspects patients need to know about, like COVID-19 vaccination and risk for COVID-19 and infectious disease, and a central resource would be beneficial.

A final thought is that in uveitis we need to be comfortable with a certain level of uncertainty. That isn’t something we talk about a lot, but it’s especially true in our field, and it’s something that younger colleagues who are just getting into uveitis will need to navigate.

SA: There’s also a growing community of Young Uveitis Specialists (YUS), an offshoot of the AUS, aimed at early-career uveitis specialists, which also provides a forum to discuss interesting cases and practice models among our own cohort (for information, contact the membership board at either arthi.venkat@gmail.com or iat7med@gmail.com).

SA: The toughest patients often stick with us, and I’ve learned some painful lessons on management along the way. What patient story has taught you something that has really stayed with you?

RM: Because we are uveitis specialists, the hard reality is that patients with severe systemic conditions (iatrogenic or de novo) can sometimes die under our care. I had a patient with refractory uveitis whom I had treated with cyclophosphamide in the old days, before we had adalimumab. The oncologist helped me, but this was before the days when we knew that beyond 35 grams of cumulative dose of cyclophosphamide, the risk of leukemia and lymphoma substantially increased. Unfortunately, a couple of years after he stopped his cyclophosphamide, the patient developed acute myelogenous leukemia and succumbed to his illness very quickly. These types of events certainly have given me pause but also taught me much humility about the limitations and risks of therapy and importance of holistic understanding of uveitis patients.

In ophthalmology, usually the worst thing that can happen is to blind a patient, but with uveitis it can be much worse in some rare cases. That’s why creating a strong referral network and a strong support network of peers and colleagues is so important.

SY: I saw a patient in fellowship in the late 2000s who had stage IV melanoma and developed a severe anterior and intermediate uveitis, and that experience showed me the capabilities of medicine in working with oncology and how that translates to ocular manifestations. It’s very challenging, but you see an interplay between systemic immunotherapy and ocular immunity. We treated him primarily locally, and he improved. Another memorable patient was an Ebola survivor whom we took care of, who amazingly survived after a lot of critical care measures that would have been difficult to come by in West Africa. He developed uveitis in the convalescent phase, and that taught me a lot about viral persistence and immunology and again how much we need to understand about other infectious pathogens that are important globally.

PL: I have an 18-year-old monocular patient who has had multiple interventions and therapies and complications stemming from all of these therapies. She has taught me that we’re taking care of these patients for life, and you will be there every step of the way with the patient and their family. You can seek a second and third opinion but sometimes no matter what you do, patients continue to lose vision. Those cases keep you up at night for years. The lesson there is that you need to find compassion for yourself and see a therapist if you need to, because there are ups and downs.

SY: Also, following up to what Dr. Lin mentioned earlier, I wanted to mention the global health physician Paul Farmer, MD, who recently passed away and who promoted the idea of “accompaniment.” Dr. Farmer talks about this word accompaniment, meaning going on a journey with our patients. Sometimes we don’t know how long the journey will be. As Dr. Moorthy pointed out, sometimes it is a very challenging journey. But Dr. Farmer talks about telling the patient, “I’ll go with you and support you on whatever journey, wherever it leads.” His recent passing was extremely tragic, yet his life and work in global health continue to inspire all of us. Walking with patients along their journey is what we seek to do from a uveitis care and quality-of-life perspective.

SA: Thank you again for all of your valuable insights. As we wrap up this session and reflect, what recent advances have most excited you, and where do you hope the field of uveitis will be in the future?

RM: Most exciting to me was the FDA approval of adalimumab for noninfectious intermediate and posterior panuveitis. The VISUAL-1 and VISUAL-1 trials were masterfully done clinical trials that have set the standard for how we do clinical trials in medicine going forward. The second advance is sustained intravitreal drug therapy. We used to only have Retisert (Bausch + Lomb), and now we have multiple other in-office options to deliver local corticosteroid therapy. We have tools that we never had before.

PL: For me, it’s long-acting steroid implants. That was revolutionary. They have high efficacy and potency, and although the side effects are not to be trifled with, these patients have failed other therapies, so just having options is huge. Also, tocilizumab (Actemra; Genentech) has been quite amazing in how it has helped refractory patients.

SY: Dr. Lin published a great editorial on biologic response modifiers and some of what’s happening from an immunologic perspective.¹ Understanding that will inform how we personalize uveitis care going forward. RP

REFERENCES

1. Kopplin LJ, Shifera AS, Suhler EB, Lin P. Biological response modifiers in the treatment of noninfectious uveitis. Int Ophthalmol Clin. 2015;55(2):19-36. doi:10.1097/IIO.0000000000000060