Efficacy and Safety of Tocilizumab in the Management of Non-Infectious Uveitis Failed with Conventional Immunomodulatory and Anti-TNFα Therapies

Abstract

Purpose:

To determine the outcomes of intravenous (IV) tocilizumab (TCZ) in patients with non-infectious uveitis who failed with conventional immunomodulatory and anti-TNFα therapies.

Methods:

Records of seven patients with non-infectious uveitis treated with monthly IV TCZ (4–10 mg/kg) or biweekly IV TCZ (8 mg/kg) were reviewed. Outcome measures were changes in visual acuity, anterior chamber cell and flare grade, vitreous haze, central subfield thickness (CST), and fluorescein angiography (FA) score.

Results:

Ten eyes of seven patients received TCZ therapy. Median age of patients was 14 (range, 7–24) score; non-infectious uveitis; years. Median duration of TCZ therapy was 15 (range, 5–32) months. Mean CST reduced from retinal vasculitis; tocilizumab 373 ± 101.0 μm to 298.2 ± 40.3 μm. Mean FA score reduced from 12.5 ± 4.3 to 3.6 ± 2.6. One patient developed elevated liver transaminases.

Conclusion:

IV TCZ is a potentially effective and safe therapeutic option for the management of refractory non-infectious uveitis.

Introduction

The term non-infectious uveitis represents a broad spectrum of intraocular inflammatory disorder that accounts for approximately 5–20% of cases of severe vision impairment in developed countries.¹ Although the clinical presentation of non- infectious uveitis can show variability depending on disease etiology, all inflammation-related changes and its complications can lead to cumulative damage to ocular tissue resulting in visual loss.² Therefore, the main target in the management of uveitis is to achieve remission and avoid recurrences to prevent structural and functional alterations in ocular tissue.

Assessment of treatment response in patients with uveitis requires a thorough ophthalmic evaluation. A standardized grading scheme for anterior chamber and vitreous inflammation was established by the Standardization of Uveitis Nomenclature (SUN) group, the most commonly used clinical marker in the assessment of uveitis.³ In addition to standardized assessment criteria in uveitis, fluorescein angiography (FA) has become essential not only in the diagnosis of uveitis but also in the evaluation of posterior segment inflammation such as retinal vessel staining and/or leakage, subclinical retinal capillary involvement, and monitoring treatment response during follow-up in patients with uveitis.⁴ To quantify and assess posterior segment inflammation in patients with uveitis, Angiography Scoring for Uveitis Working Group (ASUWOG) has created a semi-quantitative scoring system using fluorescein and indocyanine angiography.⁵

Treatment of non-infectious uveitis includes systemic or local corticosteroids, conventional immunomodulatory therapy (IMT) such as azathioprine, methotrexate, and mycophenolate mofetil, interferon-alpha and anti-tumor necrosis factor-alpha (anti-TNFα) therapy.^6–8 Anti-TNFα therapy, particularly infliximab and adalimumab, demonstrated successful outcomes in the management of recalcitrant cases when conventional IMT failed.^6,9–14 However, there is still a need for new therapeutic agents for patients who show treatment failure with anti-TNFα therapy.

Tocilizumab (TCZ; Actemra; Roche/Genentech in the US; Chugai Pharmaceutical Co. in Japan) is a recombinant humanized monoclonal antibody against interleukin-6 (IL- 6) receptor that has been approved for the treatment of various systemic inflammatory conditions such as rheumatoid arthritis, systemic and polyarticular juvenile arthritis, giant cell arthritis, and Castleman’s Disease.¹¹ Although TCZ has not been approved for the treatment of intraocular inflammation, several studies showed promising results with TCZ therapy in the management of non- infectious uveitis refractory to conventional IMT and anti- TNFα therapy.^8–15

In this retrospective study, we aim to assess the efficacy and safety of intravenous (IV) TCZ therapy in the management of non-infectious uveitis who failed with conventional IMT and anti-TNFα.

Materials and methods

The index study employed a retrospective chart review. Medical records of seven patients with non-infectious uveitis treated with IV TCZ at a university uveitis clinic were reviewed between January 2017 and March 2022. The study was conducted in compliance with the Declaration of Helsinki, the United States Code of Federal Regulations Title 21, and the Harmonized Tripartite Guidelines for Good Clinical Practice (1996). The study was approved by local institutional review boards.

Patients with non-infectious uveitis who were treated with monthly IV TCZ (4–10 mg/kg) or biweekly IV TCZ (8 mg/kg) for at least 5 months with a history of failed treatment with at least one IMT and anti-TNFα agent were included in the study.

Uveitis secondary to infectious etiology was excluded from the study. Patients with concurrent posterior segment disease such as age-related macular degeneration and retinopathy secondary to diabetes or hypertension were also excluded.

Patients’ demographics, clinical diagnosis, ocular findings, laboratory test results, and previous treatment modalities were recorded from the patient chart review. All patients underwent a complete ophthalmologic evaluation including visual acuity (VA), slit-lamp examination, fundus examination, ultra-widefield OPTOS fundus fluorescein angiography (OPTOS Plc, Dunfermline, UK), Heidelberg Spectralis SD- OCT (Heidelberg Engineering, Heidelberg, Germany) at the initial and all follow-up visits. A stepwise therapeutic approach was used to treat all patients. Tocilizumab therapy was initiated in all patients who were initially unresponsive and/or intolerant to IMT and subsequently to anti-TNFα therapy. Treatment response was assessed through a detailed ophthalmic examination and ophthalmic imaging modalities, including FA and SD-OCT at each visit. All patients were scheduled to be seen at 10- to 16-week intervals. Ophthalmic examinations and treatment plans for all patients were provided by a single uveitis specialist (QDN). Patients with systemic manifestations were managed in collaboration with rheumatology or pediatric rheumatology departments. Visual acuities in Snellen scale were converted to ETDRS letter scores for the analysis.

The Angiographic Scoring for the Uveitis Working Group (ASUWOG) system was utilized for FA scoring.⁵ The ASUWOG system is a semi-quantitative system where inflammatory signs on FA were assigned to a maximum total score of 40 and includes nine categories: optic disc hyperfluorescence, macular edema, retinal vascular staining, capillary leakage, retinal capillary non-perfusion, neovascularization of disc, neovascularization elsewhere, pinpoint leak, retinal staining, and subretinal pooling. Two experienced observers (GU and IK) assessed the FA images independently and were masked to each other’s readings. Average measurements were utilized when discrepancies occur between two graders.

All patients were tested with QuantiFERON-Tb Gold to rule out tuberculosis before the initiation of TCZ therapy. Baseline blood evaluations, including complete blood count, liver enzymes, renal function tests, lipid profile, erythrocyte sedimentation rate, and C-reactive protein, were obtained and repeated bimonthly.

Response to therapy was evaluated with changes in 1) VA, 2) AC cell and flare grade, 3) vitreous haze (VH) grade, 4) central subfield thickness (CST), and FA scoring. These outcome measures were recorded prior to TCZ initiation, after three cycles of TCZ therapy, and at final visit.

Results were expressed as the mean ± standard deviation or median (interquartile range [IQR]), as appropriate. Results were reported considering the number of affected eyes. Variables at final visit were also described but not statistically analyzed in the present study due to the variable follow-up periods.

Results

Ten eyes of seven patients with non-infectious uveitis received TCZ therapy following failed conventional IMT and anti-TNFα therapies. The median age of patients was 14 (range, 7–24) years. Three patients had bilateral uveitis. The clinical diagnosis of patients included chronic juvenile idiopathic uveitis (JIA)- associated uveitis (n: 4), idiopathic retinal vasculitis (n: 2), and HLA-B27-associated uveitis (n: 1). Demographics, clinical features, and previous medications are shown in Table 1.

Table 1.

Demographics, clinical features, and previous medications in seven patients with non-infectious uveitis.

Pt no	Age/ Sex/ Eye	Diagnosis	Previous Treatment	Reason for TCZ Initiation
1	15/F/ OD	JIA	Cs, MTX, Golimumab, ADA	Ineffectiveness
2	15/F/ OD	JIA	Cs, MTX, Golimumab, IFX, ADA	Adverse eventsIFX (difficulty in breathing),ADA (severe GI symptoms)
3	24/F/ OS	JIA	Cs, MTX, IFX, ADA	Adverse eventsIFX (GI symptoms), ADA (lung nodules)
4	14/M/ OD	HLA-B27	Cs, MTX, ADA, IFX	Ineffectiveness
5	14/M/ OU	IRV	Cs, MTX, IFX	Ineffectiveness
6	13/F/ OU	JIA	Cs, MTX, IFX	Ineffectiveness
7	7/M/ OU	IRV	Cs, MTX, IFX	Adverse events IFX (fatigue)

ADA: adalimumab, Cs: corticosteroid, F: female, GI: gastrointestinal, IFX: infliximab, IRV: idiopathic retinal vasculitis, JIA: juvenile idiopathic arthritis, M: male. MTX: methotrexate, Pt: patient, TCZ: tocilizumab.

Prior to TCZ therapy, all patients received systemic corticosteroids, conventional IMT, and biologics. The underlying reason for switching previous biologics to TCZ infusions was ongoing inflammation in four cases and adverse events in three cases. Previous medication details are shown in Table 1.

The median duration of TCZ therapy was 15 (range, 5–32) months. Intravenous TCZ therapy was started at 4 mg/kg in two patients and 8 mg/kg in five patients. The initial dose of 4 mg/kg was increased to 8 mg/kg at months 3 and 8 in patients 3 and 5, respectively, due to inadequate response. One patient (Patient 4) required a dose increase to 10 mg/kg along with IV 1000 mg methylprednisolone at month 7 due to insufficient improvement in FA. During follow-up, the patient (Patient 4) underwent pars plana vitrectomy (PPV) for further investigation, as four cycles of 10 mg IV TCV and 1000 mg methylprednisolone therapy did not provide the resolution of inflammation on FA. The result of diagnostic PPV was consistent with a chronic inflammatory process without a specific underlying disease. Hence, the patient continued with 10 mg IV TCZ therapy along with IV methylprednisolone, and the disease activity showed a remarkable improvement after three more cycles of TCZ and methylprednisolone infusions (FA score: 4).

Intravenous methylprednisolone at a dose of 500–1000 mg (1–3 days) was administered to six patients along with the TCZ infusions. Other concurrent medications include oral corticosteroids 5 mg/day in one patient and 10 mg/day in one patient, methotrexate in four patients, and mycophenolate mofetil in one patient. Table 2 provides details about IV TCZ therapy and concomitant medications.

Table 2.

Complications before tocilizumab therapy, tocilizumab therapy, and concomitant medications, in seven patients with non-infectious uveitis.

Pt no	Eye	Complications before TCZ Therapy	TCZ+MP Therapy/Duration of TCZ +MP (mo)	No of TCZ Cycles	Concurrent Medication
1	OD	-	8 mg/kg/BIW + 1 g MP/1d (5mo)8 mg/kg/BIW + 5 g MP/1d (17 mo)	23	-
2	OD	Amlyopia	8 mg/kg/BIW + 500 mg MP/1d (5mo)	10	MMF 1500 mg/d
3	OS	EPS, 1+ NS	4 mg/kg/mo+ 750 mg MP/1d (3mo)8 mg/kg/mo + 750 mg MP/1d (6mo)	9	MTX 20 mg/wk
4	OD	Aphakia	8 mg/kg/mo (7mo)10 mg/kg/mo +1000 mg MP/1d (6 mo)	14	MTX 25 mg/wk+ Pred 10 mg/ d
5	OD	Mild PSC, BK	4 mg/kg/mo+ 750 mg MP/3d (8mo)8 mg/kg/mo + 750 mg MP/1d (7mo)	13	MTX 20 mg/wk+ Pred 5 mg/d
5	OS	Mild PSC, BK	4 mg/kg/mo+ 750 mg MP/3d (8mo)8 mg/kg/mo + 750 mg MP/1d (7mo)	13	MTX 20 mg/wk+ Pred 5 mg/d
6	OD	BK, PSC, Cushingoid	8 mg/kg/mo (16mo)	18	MTX 22.5 mg/wk
6	OS	BK, PSC, Cushingoid	8 mg/kg/mo (16 mo)	18	MTX 22.5 mg/wk
7	OD	Aphakia	8 mg/kg/mo + 500 mg MP/1d (8mo)	8	-
7	OS		8 mg/kg/mo + 500 mg MP/1d (8mo)	8	-

Pt: patient, Dx: diagnosis, TCZ: tocilizumab, VA: visual acuity, CMT: central macular thickness, FA: fluorescein angiography, Int: initial, Fnl: final, MP: methylprednisolone, MMF: mycophenolate mofetil, MTX: methotrexate, NS: nuclear sclerosis, Pred: prednisone, d: day, wk: week, BIW: biweekly, mo: month.

Visual acuity improved or remained the same in all eyes. Four eyes had final VA lower than 55 ETDRS letters. Among the eyes with low final VA, one had amblyopia, one had posterior subcapsular cataract, and two eyes were aphakic before initiation of TCZ. Table 3 demonstrates VA for each patient at baseline, after three cycles of TCZ therapy and at the final visit.

Table 3.

Visual acuity, central macular thickness, and fluorescein angiography score before and after tocilizumab therapy in seven patients with non-infectious uveitis.

			VA (ETDRS)			AC Cells (0–4)			AC Flare (0–4)			VH (0–4)			CST (μm)		FA Score
Pt no	Eye	Int	3rd cycle	Fnl	Int	3rd cycle	Fnl	Int	3rd cycle	Fnl	Int	3rd cycle	Fnl	Int	3rd cycle	Fnl	Int	3rd cycle	Fnl
1	OD	65	80	80	0	0	0	2	0.5	0.5	0.5	0	0	514	289	283	16	0	0
2	OD	35	35	35	0	0	0	2	1	1	2	1	0.5	334	N/A	333	12	5	3
3	OS	70	80°	80	1	0°	0	2	1°	1	1*	1°,*	1*	N/A	321°	321	N/A	5°	3
4	OD	25	25	25	0	0	0	2	1	1	0.5	0	0	328	N/A	315	17	6	4
5	OD	85	85°	85	0	0°	0	1	0.5°	0.5	0.5	0°	0	N/A	263°	247	14	5°	3
5	OS	75	75°	80	0	0°	0	0.5	0.5°	0.5	0.5	0.5°	0.5	N/A	273°	259	14	12°	9
6	OD	25	35	35	0	0	0	1	1	1	1*	1*	1*	296	276	264	13	6	2
6	OS	70	70	70	0	0	0	1	0.5	0.5	0	0	0	293	285	267	6	2	3
7	OD	55	55	55	1	0	0	1	0.5	0.5	0.5	0.5	0.5	524	378	373	16	8	7
7	OS	85	85	85	2	0	0	2	0.5	0.5	0	0	0	322	319	320	5	2	2

Pt: patient, TCZ: tocilizumab, VA: visual acuity, CST: central subfield thickness, FA: fluorescein angiography, Int: initial, Fnl: final.

^°After 3 cycles of 4 mg TCZ infusions.

^*Presence of cataract.

Three eyes (Patients 3 and 7) had AC cells at the initial visit, whereas no patients had AC cells after three cycles of TCZ therapy and at the final visit. Patient 1, Patient 3, and Patient 4 were on topical prednisone acetate or difluprednate treatment at the initial visit, while only one patient (Patient 4) was on topical prednisolone acetate treatment at the final visit. The mean vitreous haze grade was 0.65 ± 0.6 at baseline, 0.4 ± 0.5 after three cycles of TCZ and 0.35 ± 0.4 at the final visit. Table 3 demonstrates AC cell and flare grade and VH grade for each patient at baseline, after three cycles of TCZ therapy and at the final visit.

The mean CST was 373 ± 101.0 μm at baseline, 300.5 ± 37.6 after three cycles of TCZ, and 298.2 ± 40.3 μm at the final visit. Before TCZ therapy, two eyes that had cystoid macular edema (CME) (CST > 500 μm) showed complete resolution of cysts with a normal foveal configuration at the final visit. No patients developed CME throughout the TCZ treatment. Table 3 demonstrates CST for each patient at baseline, after three cycles of TCZ therapy and at the final visit.

The mean FA score was 12.5 ± 4.3 at baseline, 5.1 ± 3.4 after three cycles of TCZ and 3.6 ± 2.6 at the final visit. All patients showed improvement in the FA inflammatory score at the final visit. Initial FA findings include disc staining/leakage (8 eyes), macular edema (8 eyes), retinal vascular staining (2 eyes), capillary leakage at posterior pole (8 eyes), and periphery (10 eyes). Table 3 demonstrates FA score for each patient at baseline, after three cycles of TCZ therapy and at the final visit. Figure 1 demonstrates representative UWF FA findings of four patients before and after IV TCZ therapy.

Figure 1.

Representative images from four study patients: Ultra-widefield fluorescein angiography images showing varying degrees of optic disc and foveal hyperfluorescence and capillary leakage at posterior pole and periphery (a, c, e, and g) prior to intravenous tocilizumab therapy. Ultra-widefield fluorescein angiography images showing normal fluorescence (b), milder optic disc hyperfluorescence and milder peripheral capillary leakage (d, f, and h) after doses of intravenous tocilizumab therapy.

Repeated infusions of TCZ were well tolerated by all subjects. One patient (Patient 7) developed mildly elevated liver transaminases, which subsequently normalized. No ocular complications developed during treatment with IV TCZ.

Discussion

Treatment of refractory non-infectious uveitis remains a clinical challenge. The main target in the management of uveitis is to achieve remission, avoid recurrences, and prevent uveitis-related complications to preserve vision. Anti-TNFα therapy has shown to be effective in the treatment of non- infectious uveitis refractory to IMT.^6,8,16–20 Nevertheless, there remain patients with non-infectious uveitis who are not responsive or are intolerant to anti-TNFα therapy. In our small number of cases in this study, we evaluated the role of IV TCZ therapy in patients with non-infectious uveitis refractory and those intolerant to conventional IMT and anti-TNFα therapy.

Treatment response and disease activity in uveitis require an ophthalmologist’s comprehensive assessment through detailed ophthalmological examination and ocular imaging modalities. Standardized outcome measures, AC cell and flare grade, and VH grade by the SUN working group are crucial parameters in the assessment of intraocular inflammation that is widely used in clinical practice and clinical studies evaluating non- infectious uveitis.³ In addition to standardized grade, FA is routinely performed in inflammatory ocular diseases and is particularly helpful in the recognition and evaluation of posterior segment involvement and uveitis-associated complications, including retinal vessel staining and/or leakage, subclinical retinal capillary involvement, retinal vascular occlusions, retinal ischemia, neovascularizations, macular edema, and optic nerve head inflammation.^4,6,21 With the routine use of FA and ultra-widefield FA in clinical practice, posterior segment involvement has become more recognized in patients diagnosed with anterior uveitis, particularly in patients with JIA- and HLA-B27-associated uveitis.^22–24 In our case series, there were four JIA-associated uveitis and one HLA-B27-associated uveitis cases, which showed ongoing subclinical retinal capillary leakage and optic nerve head staining/leakage on FA despite treatment with IMT and anti-TNFα therapy. Tocilizumab therapy showed a significant decrease in the degree of inflammation on FA findings after three cycles of TCZ infusions and at the final visit compared to baseline in most of the eyes in our case series. The severity of inflammation on FA was assessed with a semi-quantitative FA scoring system proposed by the ASUWOG.⁵ In this FA scoring system, inflammatory signs on FA were assigned to a maximum total score of 40. Among ten eyes in our study, one eye achieved a final FA score of zero (Patient 1), and the other eyes had a final FA score under ten. These favorable outcomes were also obtained from patients with a short follow-up period supporting that IV TCZ therapy provides rapid response in controlling intraocular inflammation. In parallel to our findings, previous studies evaluating the efficacy of TCZ for posterior segment inflammatory findings revealed similar outcomes. In STOP- Uveitis, a randomized, prospective, and multicenter study, the efficacy and safety of two dosages of IV TCZ infusions (4 and 8 mg/kg) were assessed in patients with active uveitis refractory to conventional IMT at month 6. The same ASUWOG FA scoring was used in the study, and 30 patients had a baseline FA inflammatory score greater than zero. Of those 30 patients, 25 showed improvement, 2 remained the same, and 3 showed a 1-point worsening in the FA score at month 6.¹² Wennick et al. reported a remarkable reduction in overall FA score from 14 at baseline to 8 and 5 at month 6 and 12, respectively, using the same ASUWOG scoring system in seven children with refractory intermediate and panuveitis treated with IV TCZ.²⁵ The same FA scoring system was utilized by Ozturk et al.¹³ in five patients with Behçet uveitis that had failed with conventional IMT, interferon-alfa, and anti-TNFα therapy. Six eyes of three patients who had follow-up FA at the final visit showed a remarkable reduction in FA scores.¹³ In addition, Atienza- Mateo et al. reported complete resolution of RV in eight eyes treated with monthly 8 mg/kg IV TCZ and weekly 162 mg subcutaneous TCZ in patients with Behçet disease after a mean follow-up of 9.5 months.¹⁵ Similarly, Maleki et al. showed resolution of retinal vasculitis between 8 and 15 months in 14 eyes with refractory JIA-associated uveitis treated with IV TCZ.²⁴

Macular edema is one of the most common complications associated with vision loss in uveitic diseases.^26–28 Several studies highlighted the importance of IL-6 in the pathophysiology of macular edema by increasing endothelial permeability and VEGF production.^28,29 This information is also supported by the significant association between intraocular IL-6 levels and the presence of macular edema in various retinal pathologies.^30,31 Additionally, TCZ therapy has been shown efficacious in several studies and case reports in the management of refractory macular edema.^{28,29,32–34} Refractory macular edema was present in two eyes in our study. In our study, similar to previously reported positive data, complete resolution of CME was observed in these two cases following initiation of TCZ. In addition, no patients developed CME during treatment with TCZ infusions.

Visual acuity showed improvement or remained stable in all eyes at the final visit in our study. Four eyes had low final visual acuity less than 55 ETDRS letters, which could be explained by amblyopia in one eye (Patient 2) and a pre-existing posterior subcapsular cataract in one eye (Patient 6). The remaining two eyes with poor visual outcomes were aphakic (Patients 4 and 7) due to previous cataract extraction before treatment with IV TCZ. The poor outcomes in visual acuity in two aphakic eyes were attributed to an uncorrected hyperopic refractive error due to aphakia, as these patients had no media opacity and maculopathy that could affect the visual outcome.

All patients in the present case series received IV TCZ therapy in combination with conventional IMT and/or systemic corticosteroids. Systemic corticosteroids were administered as monthly IV methylprednisolone at a dose of 500– 1000 mg (1–3 days) along with TCZ infusions except for one patient who had a Cushingoid appearance due to previous oral prednisone use. Two patients received low dose daily oral prednisone at 10 mg (Patient 4) and 5 mg (Patient 5). In most cases, TCZ was initiated at 8 mg/kg except for two patients in whom TCZ therapy commenced at 4 mg/kg. Although data from STOP-Uveitis study showed similar efficacy between 4 mg/kg and 8 mg/kg IV TCZ therapy in patients with uveitis, the initial dosage of 4 mg/kg TCZ was incremented to 8 mg/kg in two of our cases due to inadequate response. In that regard, IV TCZ therapy may be started at 4 mg/kg monthly doses, followed by an increase to 8 mg/kg depending on clinical response and the patient’s tolerance. Overall, patients most likely achieve better control of intraocular inflammation with monthly and biweekly 8 mg/kg IV TCZ therapy. Nevertheless, one patient (Patient 4) required dose increase to monthly 10 mg/kg IV TCZ along with IV 1000 mg methylprednisolone and underwent subsequent PPV for further investigation due to persistent disease activity. The significant improvement in FA (FA score of 4) at the final visit in that patient was attributed to a combination of IV TCZ therapy, increased oral prednisone for surgical procedure as well as PPV which was believed to reduce the inflammatory load in the vitreous. It is unlikely that the observed benefits were due to intravenous or oral corticosteroids, as the patients in our series have been previously treated with steroids (along with other IMT) and did not show improvements or resolution. However, it is possible that there are synergistic effects of combination therapy of TCZ and corticosteroids, with corticosteroids enhancing the effectiveness of TCZ alone.

Common side effects due to TCZ therapy include injection site reaction, upper respiratory symptoms, neutropenia, thrombocytopenia, elevated liver enzymes, and less frequently opportunistic infections and gastrointestinal perforation.¹¹ In our study, all patients tolerated TCZ infusions well without any serious adverse events. Only one patient developed mildly elevated liver transaminases, which subsequently returned to normal. No patients were discontinued from TCZ therapy due to side effects.

Limitations of this study include retrospective design and small sample size with variable follow-ups. However, new promising treatment modalities are of clinical importance for these challenging patients. Moreover, the index study provides valuable information on IV TCZ therapy as well as patient characteristics of non-infectious uveitis in the actual clinical practice settings that reflect the real-world population.

In conclusion, IV TCZ therapy demonstrated a considerable decrease in FA inflammatory scores and resolution of CME in patients with non-infectious uveitis resistant or intolerant to conventional IMT and anti-TNFα therapy. Most eyes, except for one eye, were able to discontinue topical prednisone acetate or difluprednate therapy at final visit. All patients tolerated TCZ infusions well without any severe side effect. Therefore, IV TCZ may be a potential therapeutic option in the management of non-infectious uveitis that failed with other medications. However, there is a need for further studies with particularly larger sample size and longer follow-up to evaluate the efficacy and safety interval of IV TCZ therapy for the management of non-infectious uveitides.