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Retinal Physician

Article

IOP Changes in Patients With Uveitis

Thoughtful monitoring and subspecialty collaborations can help minimize impact.

By: Nathan M. Radcliffe, MD, Veeral S. Sheth, MD, MBA, FACS
Retinal Physician September 1, 2021 Vol 18, Issue September 2021 Page(s): 28-30

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Uveitis is one of the most confounding diseases that ophthalmologists are tasked with managing. If left untreated, scar tissue may disrupt aqueous outflow, leading to uveitic glaucoma. Corticosteroid therapy for uveitis, on the other hand, may lead to elevations in intraocular pressure (IOP) that induce glaucoma. The key, then, is to strike a balance in managing uveitis — controlling inflammation without fostering dangerous elevations in IOP. Collaboration between a retina or uveitis specialist and a glaucoma specialist may be needed in some cases. Effective communication will allow patients with uveitis experiencing pressure-related complications to receive safe and effective therapy.

UVEITIS AND PRESSURE CONCERNS

Ocular hypertension and glaucoma secondary to uveitis may develop as a result of inflammatory processes and scarring in the trabecular meshwork. Chronic use of corticosteroids may also result in reduced aqueous outflow in these patients.1 Steroids may interfere with the production and destruction of proteins that compose the extracellular matrix of the trabecular meshwork, producing a disruption to outflow patterns that results in elevated IOP.

Use of steroids in patients with uveitis starts with assessing a patient’s response to therapy. Topical steroids are often an effective first-line treatment that also indicate whether a patient will respond adversely to steroid therapy. If a patient’s IOP rises too high during topical therapy, then systemic nonsteroidal immunomodulatory therapy may be warranted.

If topical steroids effectively reduce uveitic inflammation and do not significantly affect a patient’s IOP over several months of therapy, then treatment with an intravitreal steroid implant may be warranted. Intravitreal steroid implants slowly elute medication over time, obviating compliance concerns and providing a steady, low dose of therapy. In the United States, the fluocinolone acetonide intravitreal implant 0.59 mg (Retisert; Bausch + Lomb), the dexamethasone intravitreal implant 0.7 mg (Ozurdex; Allergan), and the fluocinolone acetonide intravitreal implant 0.18 mg (Yutiq; Eyepoint Pharmaceuticals) are approved for the treatment of noninfectious uveitis affecting the posterior segment.

In our experience, the periods of drug release for these implants are approximately 36, 30, and 6 months for Yutiq, Retisert, and Ozurdex, respectively. It should be noted that Retisert requires surgical implantation, whereas Yutiq and Ozurdex are administrated intravitreally in a clinical setting. Given the longer duration of therapy and the easier route of administration, we commonly employ Yutiq therapy for patients with chronic noninfectious uveitis.

In a 2013 retrospective, real-world study of patients with uveitis treated with either Retisert or Ozurdex and followed for >6 months, IOP elevations and interventions to control IOP were more common in the Retisert group (with 44% of Retisert-treated eyes needing additional IOP-lowering medications or surgery).2 In 2020, Jaffe et al published a comparison of Yutiq and sham therapy for uveitis and found that mean IOP was similar for both groups at 36 months, with a higher rate of IOP-lowering medication use in the Yutiq group but a higher rate of surgical intervention in the sham group.3 A post-hoc analysis of significant IOP elevations (≥30 mmHg) found a similar course between Yutiq-treated and sham-treated eyes, with most IOP spikes managed medically; further, the insert had no apparent impact on the progression of visual field loss in the subset of eyes with significant IOP elevation when compared to fellow eyes.4

Each patient’s response to steroids is individual, and there are no obvious clinical characteristics that predict outcomes. Patient history, if available, may prove useful in determining a course of therapy.

THE ANATOMY OF INTERSPECIALTY COMMUNICATION

Due to concerns regarding elevated IOP, pressure checks in patients with uveitis undergoing steroid therapy should be performed at each visit. If a patient demonstrates pressure elevations that are worthy of referral, then prompt collaboration between the retina or uveitis specialist and the glaucoma specialist is needed.

Initiating medical IOP-lowering therapy in the time between referral and consultation can be appropriate (see sidebar). However, if a patient has been in the care of a glaucoma specialist, the retina or uveitis specialist should consider communicating with their ophthalmic counterpart to determine which therapeutic strategy is most prudent.

Communication via an electronic health record system is usually sufficient; in some cases, a telephone briefing is needed. Regardless of communication medium, the referring clinician should provide history and context for the glaucoma specialist so that they can accurately assess a patient’s risk of developing complications from elevated IOP.

THE GLAUCOMA CONSULT

Patients who are referred to a glaucoma specialist may not, in fact, have glaucoma. Uveitic eyes without a history of optic nerve damage that manifest elevated IOP in the presence of steroids should be considered to have steroid-induced ocular hypertension. In these patients, a glaucoma specialist has more leeway and time to manage the IOP. In eyes with a history of optic nerve damage, swift decision-making is key to successful intervention.

Some incidents of elevated IOP are transient and adequately addressed with medical therapy. In other cases, laser-based or surgical procedures must be performed. Before determining if (and which type of) intervention is appropriate, a glaucoma specialist would perform a routine clinical evaluation that includes assessments of the drainage angle, corneal thickness, IOP, OCT imaging of the macula and optic nerve, and a visual field test.

In some cases, a referring uveitis specialist initiates therapy with an aqueous suppressant such as dorzolamide, timolol, or brimonidine (or a combination thereof) to address IOP elevations. If such therapy is sufficient, then the patient may be referred back to the uveitis specialist promptly or after 1 or 2 follow-up visits. In the event that aqueous suppressants are ineffective, patients may require alternative treatments to reduce IOP.

Which Therapy Should We Start With?

For some patients, initiation of glaucoma therapy before the patient visits the glaucoma specialist is needed. Here is how we usually manage such instances.

Nathan M. Radcliffe, MD: I am happy when I hear that a uveitis specialist with whom I am collaborating has begun localized steroid therapy for uveitis treatment. We have such strong options in this space, after all — it makes sense to use them. If a uveitis specialist wishes to prescribe a patient with a history of glaucoma to a regimen of prostaglandin analogs, I think it is OK as long as they are scheduled for a glaucoma consultation and have well controlled inflammation.

Veeral Sheth, MD, MBA, FACS: I tend to employ dorzolamide in the time between seeing my patient and their meeting with a glaucoma specialist, because the drug has a short list of possible side effects and may also address macular edema present in some patients. I defer to my glaucoma specialist colleague to determine if a more aggressive therapy should be employed.

Some clinicians are reluctant to use prostaglandin analogs in this patient population due to concerns about intraocular inflammation or macular edema. However, this class of drugs remains a reliable first-line therapy for once-daily treatment of glaucoma or ocular hypertension, and need not be ruled out in the setting of uveitis.

Selective laser trabeculectomy (SLT) is safe and effective at reducing steroid-induced IOP elevations in patients whose inflammation is well controlled.5,6 Incisional surgery to address glaucoma in patients with uveitis is generally not considered until SLT has been performed or ruled out. Patients presenting with any level of nerve damage may be particularly well suited for SLT, which, it is worth mentioning, achieves an IOP-lowering effect without the burden of patient adherence to topical drops.

After application of SLT or the initiation of another therapy, a glaucoma specialist may wish to see the patient a few times for follow-up exams. After those initial follow-ups, most patients are stable and further ocular care may be transferred back to the referring uveitis or retina specialist.

Some readers may wonder if use of minimally invasive glaucoma surgery (MIGS) technology is appropriate in these patients. Recent evidence shows that Kahook goniotomy (New World Medical, a nonstent MIGS procedure) can be effective in patients with ocular inflammation and elevated IOP, and therefore some patients whose inflammation is well controlled are suited for MIGS to control chronic elevated IOP secondary to uveitic glaucoma.7

The literature shows that few MIGS stents have been studied in the management of glaucoma secondary to uveitis, although some potential has been demonstrated.8 In a 2015 study, use of the MIGS device Xen 45 (Allergan) in 24 patients with uncontrolled uveitic glaucoma allowed 83% to avoid conventional glaucoma filtration surgery for at least 12 months.9 Still, addressing uveitic glaucoma with MIGS should be done on a patient-by-patient basis until further research can be used as guidance.

COLLABORATION AND COMMUNICATION ARE KEY

Patients with glaucoma in the setting of uveitis should be handled with care. Recall that these patients face a tall order, as they are asked to juggle the discomfort associated with uveitis, the need for prompt glaucoma care, and the requirement to see a new clinician. Let them know that you’re communicating with your ophthalmic counterpart. That message — a communication on communication — may help your patient understand how much behind-the-scenes work is occurring. RP

Nathan M. Radcliffe, MD, is a member of the Microincisional Glaucoma Surgery Center at New York Eye and Ear Infirmary and is in private practice at the New York Eye Surgery Center. Dr. Radcliffe reports consultancy to Allergan, Alcon, Glaukos, New World Medical, EyePoint Pharmaceuticals, and Bausch + Lomb. Reach him at drradcliffe@gmail.com. Veeral Sheth, MD, MBA, FACS, is a clinical assistant professor at the University of Illinois at Chicago and a partner and director of clinical trials at University Retina in Chicago. Dr. Sheth reports speaker’s fees from Genentech; consultancy to Alimera Sciences, EyePoint Pharmaceuticals, Genentech, and Novartis; and research for Alimera Sciences, Allergan, Chengdu Kanghong, DRCR Retina Network, Genentech, Gyroscope, Ionis, IVERIC bio, NGM Biopharmaceuticals, Novartis, Regeneron, SalutarisMD, Santen, and SamChungDang. Reach him at vsheth@gmail.com.

REFERENCES

  1. Feroze KB, Khazaeni L. Steroid induced glaucoma. In: StatPearls. Treasure Island (FL): StatPearls Publishing; July 17, 2021.
  2. Arcinue CA, Cerón OM, Foster CS. A comparison between the fluocinolone acetonide (Retisert) and dexamethasone (Ozurdex) intravitreal implants in uveitis. J Ocul Pharmacol Ther. 2013;29(5):501-507. doi:10.1089/jop.2012.0180
  3. Jaffe GJ, Pavesio CE; Study Investigators. Effect of a fluocinolone acetonide insert on recurrence rates in noninfectious intermediate, posterior, or panuveitis: three-year results. Ophthalmology. 2020;127(10):1395-1404. doi:10.1016/j.ophtha.2020.04.001
  4. Singer M. Fluocinolone acetonide intravitreal insert for non-infectious posterior uveitis: analysis of significant IOP elevation. Presented at: the American Academy of Ophthalmology Annual Meeting; October 12-15, 2019; San Francisco, CA.
  5. Bennedjai A, Theillac V, Akesbi J, et al. The Effect of Selective Laser Trabeculoplasty on Intraocular Pressure in Patients with Dexamethasone Intravitreal Implant-Induced Elevated Intraocular Pressure. J Ophthalmol. 2020;2020:3439182. Published 2020 Oct 13. doi:10.1155/2020/3439182
  6. Radcliffe R. Selective laser trabeculoplasty (SLT) for the reduction of elevated intraocular pressure (IOP) associated with fluocinolone acetonide (FAc) intravitreal implants. Poster presented at: ARVO 2017, May 7-11, 2017; Baltimore, MD.
  7. Miller VJ, Young CEC, SooHoo JR, et al. Efficacy of goniotomy with Kahook Dual Blade in patients with uveitis-associated ocular hypertension. J Glaucoma. 2019;28(8):744-748. doi:10.1097/IJG.0000000000001298
  8. Kesav N, Palestine AG, Kahook MY, Pantcheva MB. Current management of uveitis-associated ocular hypertension and glaucoma. Surv Ophthalmol. 2020;65(4):397-407. doi:10.1016/j.survophthal.2019.12.003
  9. Sng CC, Barton K. Mechanism and management of angle closure in uveitis. Curr Opin Ophthalmol. 2015;26(2):121-127. doi:10.1097/ICU.0000000000000136

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