Key takeaways:
- One specialist highlighted circumstances through which systemic remedies, similar to corticosteroids, are higher.
- One other shared proof of improved outcomes with intravitreal implants.
SEVILLE, Spain — Therapies for uveitic macular edema, together with systemic and native choices, had been among the many matters debated on the Congress on Controversies in Ophthalmology.
Macular edema develops in as much as 30% of uveitic eyes and is essentially the most prevalent issue contributing to visible impairment in sufferers with uveitis.
Information had been derived from Debate 1: Systemic remedy is the most suitable choice to regulate uveitic macular edema. Offered at: Congress on Controversies in Ophthalmology; April 4-5, 2025; Seville, Spain.
Administration refers to 2 medical situations: treating the acute part and stopping long-term recurrences.
For native therapy, there are at present two choices for the acute part, periocular triamcinolone or Ozurdex (dexamethasone intravitreal implant, AbbVie). Iluvien (fluocinolone acetonide intravitreal implant 0.19 mg, ANI Prescribed drugs) is accessible to stop recurrence for long-term therapy, Alejandro Fonollosa, MD, mentioned.
The systemic method to treating the acute part additionally depends on two choices: oral steroids or pulse remedy. Prevention of long-term recurrences has a number of potential therapy choices.
“There are typical immunosuppressive medication — lots of them — and we even have biologics,” Fonollosa mentioned.
Systemic is healthier in a number of conditions
There are a number of well-defined conditions through which systemic therapy is a “extra affordable” alternative, in line with Fonollosa.
These situations embrace bilateral circumstances as a result of a systemic drug routine is extra sensible and extra comfy; aphakic sufferers or sufferers with capsule rupture due to the documented danger of migration of intraocular implants; circumstances with non-controlled glaucoma or with a broken optic nerve due to the danger of hypertension; and younger sufferers, particularly if earlier native remedies have been tried, due to the danger of cataract, he mentioned.
He additionally highlighted circumstances through which there isn’t a clear prognosis and an infection could possibly be an underlying etiology, in addition to circumstances through which a systemic immune illness needs to be handled on the identical time.
Systemic therapy is beneficial for recurrent edema along with two different conditions which may be encountered. One in every of these conditions can be a affected person who could current with very extreme and hyperacute manifestations, similar to ischemic vasculitis or macular inflammatory lesions.
“I might not use Iluvien in these circumstances … as a result of it lasts for 3 years roughly, however typically the period is much less, and we can not predict the period of Iluvien. If we’ve managed most of these circumstances solely with native therapy, we could have irreversible injury after a flare,” Fonollosa mentioned.
The second scenario happens when macular edema is related to choroidal illness due to the poor impact of Iluvien on the choroid.
The MUST research confirmed comparable efficacy of Retisert (fluocinolone acetonide intravitreal implant 0.59 mg, Bausch + Lomb) vs. systemic corticosteroid therapy over 5 years.
Restricted information from medical trials is accessible for immunosuppressants. The FAST research in contrast mycophenolate mofetil vs. methotrexate and located related efficacy at 12 months. Anti-tumor necrosis issue (TNF) was additionally examined for uveitic macular edema in a research in Switzerland, exhibiting discount of thickness of the macula.
Biologics are an much more promising possibility.
“Some years in the past, Alfredo Adán and his group confirmed the nice efficacy of blocking IL-6 … and this has been replicated in different research,” Fonollosa mentioned. “A research from a French group confirmed that tocilizumab is healthier than anti-TNF medication. That is necessary as a result of it reveals that this cytokine is pivotal within the pathogenesis of macular edema.”
When potential, native is simpler
Corticosteroids are first-line therapy for uveitic macular edema as a result of they forestall leukocyte migration, stabilize the endothelial tight junctions, and inhibit the synthesis of VEGF and different pro-inflammatory cytokines. Nevertheless, they’ve a variety of issues, Zohar Habot-Wilner, MD, mentioned.
“They enhance the danger of diabetes, hypertension, osteoporosis, compression fractures and even aseptic hip necrosis. They could trigger GI issues similar to peptic ulcer, endocrine issues like adrenal insufficiency and Cushing’s syndrome, and in children, very importantly, progress retardation,” she mentioned.
She additionally talked about dermatologic issues, together with pimples and subcutaneous tissue atrophy, and results on the immune system, resulting in excessive susceptibility to infections and delayed wound therapeutic.
“We ought to be very cautious, as typically drug-induced issues could also be much more extreme than the illness itself,” she mentioned.
The choice possibility is intravitreal corticosteroids, which ought to be thought-about when the affected person refuses systemic corticosteroids, if the illness is proscribed to the attention, in pregnant girls and in kids.
“All of us are accustomed to the intravitreal dexamethasone implant. We use it lots, and research present favorable outcomes for uveitic macular edema,” Habot-Wilner mentioned.
Normally, in her expertise, the macular edema resolves fully, though research have proven that in 40% to 70% of circumstances a second injection could be wanted in a median time-frame of 6 to 10 months.
Constructive outcomes have been reported additionally in vitrectomized eyes and in kids, though cautious monitoring is required for the danger of IOP elevation and cataract. The MUST trial confirmed higher quantitative enchancment with the fluocinolone acetonide implant as in contrast with systemic therapy, she mentioned.
“From the MUST trial, we are able to clearly see that extra critical systemic opposed occasions include using systemic therapy,” Habot-Wilner mentioned. “These embrace hyperlipidemia, hypertension, diabetes, osteopenia, osteoporosis and fractures. The sufferers that had been handled with systemic therapy had additionally some ocular points, similar to glaucoma, excessive strain and cataracts.”
As well as, 68% of the systemic group vs. 25% of the implant group obtained at the very least one supplemental regional corticosteroid injection.
The nonbiodegradable, injectable Iluvien and Yutiq (fluocinolone acetonide intravitreal implant 0.18 mg, ANI Prescribed drugs) implants have a protracted period of motion of as much as 36 months and have fewer unwanted side effects in contrast with Retisert. Habot-Wilner confirmed outcomes from a real-life research of the French Uveitis Community through which Iluvien led to important enchancment of edema and visible acuity over 12 months, with few circumstances of ocular hypertension and no want for rescue therapy within the majority of eyes.
Nevertheless, the perfect remedy specialists are trying ahead to is a drug that doesn’t include corticosteroids, and there are excessive expectations for vamikibart (Roche), an anti-IL-6 monoclonal antibody particularly engineered for intravitreal use.
“It has a half-life of seven days, it restores the blood-retinal barrier integrity, it inhibits each cis- and trans-IL-6 signaling, and it has longer pharmacokinetics within the vitreous physique by way of intravitreal injection moderately than systemic injection,” Habot-Wilner mentioned.
The part 1 DOVETAIL trial included 37 grownup sufferers with lively or inactive uveitic macular edema of a number of etiologies and confirmed promising outcomes with totally different doses of vamikibart.
“With all doses, there was imaginative and prescient enchancment and discount in retinal thickness. The drug was effectively tolerated, with no associated critical opposed occasions or any new cataracts,” she mentioned.
The part 3 MEERKAT and SANDCAT trials are at present evaluating the efficacy, security, pharmacokinetics and pharmacodynamics of intravitreal vamikibart in sufferers with uveitic macular edema secondary to noninfectious uveitis.
“We’re all trying ahead to the outcomes of those attention-grabbing and necessary research,” Habot-Wilner mentioned.
One other research is evaluating using intravenous or subcutaneous injections of anti-TNF alpha (infliximab and adalimumab) vs. tocilizumab within the therapy of uveitic macular edema refractory to systemic corticosteroids.
“Solely 22% of the sufferers that had the anti-TNFs achieved full macular edema decision whereas a 3rd of the sufferers that had been handled with tocilizumab achieved this outcome. We could conclude that tocilizumab is healthier than anti-TNFs, however the general outcomes are comme ci, comme ça,” Habot-Wilner mentioned. “I can conclude that systemic remedy shouldn’t be at all times the most suitable choice for uveitic macular edema.”
References:
- Adán A, et al. Retina. 2013;doi:10.1097/IAE.0b013e31827e247b.
- Ajamil-Rodanes S, et al. Br J Ophthalmol. 2022;doi:10.1136/bjophthalmol-2020-317372.
- Barry RJ, et al. Cochrane Database Syst Rev. 2018;doi:10.1002/14651858.CD012577.pub2.
- Bograd A, et al. Ocul Immunol Inflamm. 2023;doi:10.1080/09273948.2022.2075761.
- Feenstra D. et al. Summary 5189, posterboard B0163. Offered at: Affiliation for Analysis in Imaginative and prescient and Ophthalmology assembly; April 23-27, 2023; New Orleans.
- Habot-Wilner Z, et al. Ophthalmologica. 2014;doi:10.1159/000362178.
- Jabbour M, et al. J Pers Med. 2024;doi:10.3390/jpm14030245.
- Jimenez YP, et al. Ocul Immunol Inflamm. 2024;doi:10.1080/09273948.2024.2395289.
- Khurana RN, et al. Retina. 2015;doi:10.1097/IAE.0000000000000515.
- Leclercq M, et al. Ophthalmology. 2022;doi:10.1016/j.ophtha.2021.11.013.
- McDonough AK, et al. Curr Opin Rheumatol. 2008;doi:10.1097/BOR.0b013e3282f51031.
- Mesquida M, et al. Retina. 2018;doi:10.1097/IAE.0000000000001690.
- Mukai R, et al. BMC Ophthalmol. 2022;doi:10.1186/s12886-022-02617-2.
- Mukai R, et al. BMC Ophthalmol. 2024;doi:10.1186/s12886-024-03663-8.
- Multicenter Uveitis Steroid Remedy (MUST) Trial Analysis Group, et al. Ophthalmology. 2015;doi:10.1016/j.ophtha.2015.06.042.
- Pelegrín L, et al. Eye (Lond). 2015;doi:10.1038/eye.2015.73.
- Sella R, et al. Graefes Arch Clin Exp Ophthalmol. 2015;doi:10.1007/s00417-015-3124-x.
- Sorkin N, et al. Ophthalmologica. 2014;doi:10.1159/000360304.
- Tomkins-Netzer O, et al. Am J Ophthalmol. 2016;doi:10.1016/j.ajo.2015.09.036.
- Tomkins-Netzer O, et al. Ophthalmology. 2015;doi:10.1016/j.ophtha.2015.07.036.
- Tsui E, et al. Ophthalmology. 2022;doi:10.1016/j.ophtha.2022.02.002.
Sources/Disclosures
Collapse
Fonollosa A, et al. Debate 1: Systemic remedy is the most suitable choice to regulate uveitic macular edema. Offered at: Congress on Controversies in Ophthalmology; April 4-5, 2025; Seville, Spain.
Disclosures:
Fonollosa and Habot-Wilner report no related monetary disclosures.
