Macular edema associated with non-infectious uveitis: pathophysiology, etiology, prevalence, impact and management challenges

Figures & data

Table 1 Anatomic Classification of uveitis following the International Uveitis Study Group classification system (SUN*).

Type of uveitis	Primary site of inflammation†	Includes
Anterior uveitis	Anterior chamber	Iritis
		Iridocyclitis
		Anterior cyclitis
Intermediate uveitis	Vitreous	Pars planitis
		Posterior cyclitis
		Hyalitis
Posterior uveitis	Retina or choroid	Focal, multifocal, or diffuse choroiditis
		Chorioretinitis
		Retinochoroiditis
		Retinitis
		Neuroretinitis
Panuveitis	Anterior chamber, vitreous and retina or choroid
* SUN = Standardization of uveitis nomenclature. † As determined clinically

Note: Reprinted from the American Journal of Opthalmology, Volume 140, Issue 3, Jabs DA, Nussenblatt RB, Rosenbaum JT, Standardization of Uveitis Nomenclature (SUN) Working Group, Standardization of uveitis nomenclature. Results of the First International Workshop, 509-516, copyright (2005), with permission from Elsevier.⁵

Table 2 The SUN* Working Group Descriptors of Uveitis.

Category	Descriptor	Comment
Onset	Sudden
	Insidious
Duration	Limited	Uveitis lasting <3 months
	Persistent	Uveitis lasting >3 months
Course	Acute	Episode characterized by sudden onset and limited duration
	Chronic	Repeated episodes separated by periods of inactivity without treatment, lasting >3 months
	Recurrent	Persistent uveitis with relapse in <3 month·, after discontinuing treatment
*SUN = Standardization of uveitis nomenclature.

Note: Reprinted from the American Journal of Opthalmology, Volume 140, Issue 3, Jabs DA, Nussenblatt RB, Rosenbaum JT, Standardization of Uveitis Nomenclature (SUN) Working Group, Standardization of uveitis nomenclature. Results of the First International Workshop, 509-516, copyright (2005), with permission from Elsevier.⁵

Figure 1 Macular edema secondary to intermediate uveitis in a 58-year-old male patient (left eye). (A) OCT. (B) FFA – typical petaloid pattern.

Abbreviations: OCT, optical coherence tomography ; FFA, fundus fluorescein angiography.

Figure 2 Macular edema secondary to UGH syndrome in a 60-year-old male patient (right eye).

Abbreviation: UGH, uveitis-glaucoma-hyphema.

Table 3 Non-infectious UME. Summary of the most important studies

Study	Design	Number of patients/eyes	Key results
Vallet et al^Citation145 (2016)	Multicenter, observational, infliximab vs adalimumab	160 patients	1. Mean response to treatment: 90% 2. Mean complete response: 27% 3. Median time to response: 2 months 4. Rate of serious adverse events: 13% 5. Both treatment are equivalent
Diaz-Llopis et al^Citation146 (2012)	Prospective case series adalimumab in refractory uveitis 39 JIA, 16 pars planitis, 13 Adamantiades –Behçet	131 patients	1. Mean visual acuity at baseline: 0.38±0.44 logMAR improved to 0.26±0.39 logMAR at month 6. 2. Mean macular thickness reduction from 296.95 μm±102 to 240.11 μm±36.1 3. 40 patients had clear visible cystic changes initially 4. 28 of these 40 patient had complete regression of Cystoid ME 5. Improvement of macular edema was significantly correlated with visual acuity
Arida et al^Citation144 (2011)	Meta-analysis infliximab and Adamantiades–Behçet’s disease	369 patients	1. 89% response to infliximab vs 60% etanercept (ten patients) 2. 65% complete response 3.Combination of cyclosporine A and/or azathioprine seem to have better outcome than Infliximab alone
Calvo-Rio et al^Citation147 (2011)	Multicenter, anti-TNF-alpha and Adamantiades–Behçet disease	124 patients (221 eyes)	Anti-TNF-alpha used in combination with conventional immunosuppressive treatment At baseline 80 eyes with macular thickening and 49 eyes with cystoid macular edema. Macular edema decreased from 420 μm±119.5 to 271 μm±45.6. Complete response after 12 months: 67.7%
Mesquida et al^Citation148 (2018)	Retrospective: tocilizumab for refractory uveitic macular edema (non-infectious)	16 eyes of 12 patients	Mean visual acuity at baseline 0.78±0.18 logMAR improved to 0.42±0.17 logMAR at month 12. Mean macular thickness reduction was 274 μm at month 12. Mean duration of macular edema: 13.2 years
Calvo-Rio et al^Citation149 (2016)	Open-label, multicenter study. Golimumab for spondyloarthritis-related uveitis	15 patients (18 eyes)	Visual acuity improved from 0.62±0.3 to 0.84±0.3 after 2 months Macular edema decreased from 295 μm±42.2 to 259.2 μm±10.3
Jaffe et al^Citation162 (2016)	Multicenter, multinational Phase III study, adalimumab in non-infectious uveitis	110 patients adalimumab group vs 107 placebo group	Median time to treatment failure: 13 weeks in placebo group vs 24 weeks in adalimumab group Risk of macular edema recurrence is 67% lower in case of previous treatment with adalimumab
Thorne et al for the MUST Research Group^Citation114 (2019)	Multicenter, randomized clinical trial	192 patients (235 eyes with UME)	Intravitreal triamcinolone acetonide and intravitreal dexamethasone implant had larger reductions in central subfield thickness than periorbital triamcinolone. Intravitreal dexamethasone implant was noninferior to intravitreal triamcinolone at 8 weeks. The risk of having IOP≥24 mmHg was higher in the intravitreal treatment groups compared to the periocular group. No significant difference between the two intravitreal treatment groups was found.

Abbreviation: JIA, juvenile idiopathic arthritis.

Figure 3 Treatment algorithm for non-infectious uveitic macular edema.

Abbreviations: UME, uveitic macular edema; AZA, azathioprine; MTX, methotrexate; MMF, mycophenolate mofetil; IFN, interferon-alpha; PPV, pars plana vitrectomy.

Jabs DA, Nussenblatt RB, Rosenbaum JT, Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol. 2005;140(3):509–516. doi:10.1016/j.ajo.2005.03.057

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Mesquida M, Molins B, Llorenc V, et al. Twenty-four month follow-up of tocilizumab therapy for refractory uveitis-related macular edema. Retina. 2018;38(7):1361–1370. doi:10.1097/IAE.0000000000001690

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Thorne JE, Sugar EA, Holbrook JT, et al. Periocular triamcinolone vs. intravitreal triamcinolone vs. intravitreal dexamethasone implant for the treatment of uveitic macular edema: the PeriOcular vs. INTravitreal corticosteroids for uveitic macular edema (POINT) trial. Ophthalmology. 2019;126(2):283–295. doi:10.1016/j.ophtha.2018.08.021

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