Idiopathic Posterior Scleritis Complicated by Optic Perineuritis and Ocular Motility Disorder Successfully Controlled with Adalimumab: A Case Report

Abstract

Introduction

This report describes a rare case of idiopathic orbital inflammation with posterior scleritis complicated by optic perineuritis and ocular motility disorder.

Case Presentation

A 22-year-old woman presented with right ocular pain, eyelid swelling, and blurring of vision for 5 days. Her best corrected visual acuity was 20/20 in the right eye, although a myopic shift was noted. An ocular motility disorder was identified on examination. Slit lamp and fundus examinations revealed diffuse scleral injection, anterior chamber inflammation, and serous retinal detachment. B-scan ultrasound showed thickening of the choroid and sclera. Gadolinium-enhanced magnetic resonance imaging revealed marked thickening and enhancement of the right optic nerve sheath. Humphrey visual field testing showed an enlarged blind spot and an inferior field defect. The systemic workup and laboratory tests were unremarkable, aside from elevated CRP and ESR. The patient was diagnosed with idiopathic orbital inflammation with posterior scleritis, optic perineuritis, and ocular motility disorder. Treatment with oral prednisolone (50 mg/day) improved all ocular findings, but a relapse occurred while tapering to 10 mg/day. The symptoms resolved after increasing the dose of prednisolone, and adalimumab was added to prevent recurrence. Adalimumab was continued while tapering prednisolone and replacing it with oral hydrocortisone for secondary adrenal insufficiency. Six months after the discontinuation of prednisolone, the patient remains in remission.

Conclusion

This rare case of idiopathic orbital inflammation with posterior scleritis, optic perineuritis, and ocular motility disorder was successfully controlled with adalimumab after relapse, suggesting its efficacy in preventing recurrence.

Introduction

Posterior scleritis is a severe form of scleritis, accounting for approximately 2%–12% of all cases of scleritis. Meanwhile, optic perineuritis is a rare inflammatory disorder characterized by inflammation confined to the optic nerve sheath, which can be idiopathic or secondary to an underlying systemic autoimmune disorder [1]. Optic perineuritis may present with orbital signs and symptoms, such as ophthalmoplegia and ptosis, but rarely with intraocular lesions, such as scleritis and episcleritis [1]. Both scleritis and perineuritis are recognized clinical subtypes of idiopathic orbital inflammation [2, 3], although cases simultaneously presenting with both forms are relatively rare. In representative case series of posterior scleritis – including those by Lavric et al. [4] and McCluskey et al. [5] – no cases of concurrent optic perineuritis were reported. Furthermore, Yuen and Rubin [6] reported that 65 patients with idiopathic orbital inflammation had isolated dacryoadenitis (32%), isolated myositis (29%), orbital apex syndrome (9%), concurrent dacryoadenitis and myositis (8%), and others (22%). However, they did not specify the frequencies of scleritis or optic perineuritis, suggesting that these manifestations were relatively uncommon.

This report describes a rare case of idiopathic orbital inflammation with posterior scleritis, complicated by optic perineuritis and ocular motility disorder. The disease relapsed during steroid tapering, but this was subsequently well controlled with the use of adalimumab.

Case Presentation

A 22-year-old woman presented with right ocular pain, eyelid swelling, blurring of vision, and headache. She had a history of right iritis 10 years ago. Upon examination, her best corrected visual acuity was 20/20 in the right eye (−2.00 D myopia) and 20/17 in the left eye without correction, with normal intraocular pressure bilaterally. A slit lamp examination of the right eye revealed diffuse scleral injection, conjunctival chemosis, shallow anterior chamber, anterior chamber cell 2+, and fine keratic precipitates (shown in Fig. 1a). B-scan ultrasonography of the right eye revealed choroidal and scleral thickening, along with a positive T sign (shown in Fig. 1b). Fundoscopy revealed serous retinal detachment of the right eye (shown in Fig. 1c). Optical coherence tomography revealed increased choroidal thickness, choroidal folds, and subretinal fluid (shown in Fig. 2a). Anterior segment examination and fundoscopy of the left eye revealed no abnormalities. The Hess test revealed a marked ocular motility disorder of the right eye (shown in Fig. 3a).

Fig. 1.

Ophthalmic findings of the right eye at disease onset. a Slit lamp photographs showing diffuse scleral injection, conjunctival chemosis, and a shallow anterior chamber. b B-scan ultrasonography of the left eye showing diffuse posterior scleral thickening (triangle), serous retinal detachment (arrow), and a positive T sign. c Wide-field fundus photography showing serous retinal detachment involving the peripapillary region and the area superior to the optic disc. There was no optic disc hyperemia or swelling. d Humphrey visual field test indicating enlargement of the blind spot and an inferior visual field defect.

Fig. 2.

Serial findings on optical coherence tomography. a At the initial visit, optical coherence tomography showing increased choroidal thickness, choroidal folds, and serous retinal detachment. b Two weeks after initiation of oral prednisolone, optical coherence tomography showed resolution of choroidal folds, normalization of choroidal thickness, and disappearance of subretinal fluid. Disruption of the ellipsoid zone and interdigitation zone was observed. c At the final visit, optical coherence tomography showed no retinal abnormalities or choroidal thickening.

Fig. 3.

Serial changes of both eyes on the Hess chart. a At initial presentation, ocular motility of the right eye was limited in all directions. b At recurrence, the right eye again showed limited movement in all directions, which was more pronounced compared to the initial visit. c At the final follow-up, the right eye showed a marked improvement in ocular motility, with no residual limitation.

Gadolinium-enhanced MRI revealed circumferential enhancement of the right sclera alongside prominent thickening and enhancement of the right optic nerve sheath. There were no apparent enlargements or inflammatory changes in the extraocular muscles. Mild signal elevation and contrast enhancement were observed in the subcutaneous adipose tissue around the right eyelid (shown in Fig. 4a). The critical flicker fusion frequencies (CFFs) were 24.7 and 33.8 Hz in the right and left eyes, respectively. Given that the normal adult CFF is approximately 35–40 Hz, the right eye displayed a marked reduction consistent with optic nerve dysfunction, whereas the value in the left eye was near the lower limit of normal. Humphrey visual field testing revealed an enlarged blind spot and an inferior visual field defect in the right eye (shown in Fig. 1d).

Fig. 4.

Serial findings on fat-suppressed gadolinium-enhanced T1-weighted orbital magnetic resonance imaging. a At the initial presentation, the right globe showed near-circumferential scleral thickening with contrast enhancement (arrow). The right optic nerve sheath showed thickening and enhancement (arrowhead), with no signal abnormality or enhancement of the optic nerve itself. No significant enlargement or inflammatory changes were observed in the extraocular muscles. Mild signal elevation and contrast enhancement were noted in the subcutaneous fat around the right eyelid. b Three weeks after the initial visit, during oral corticosteroid treatment (prednisolone 45 mg/day), the scleral thickening and enhancement in the right eye were nearly resolved. The thickening and enhancement of the right optic nerve sheath were also attenuated. The signal elevation and enhancement in the subcutaneous fat around the right eyelid have nearly disappeared. c Five months after the initial visit, while tapering (prednisolone 10 mg/day), there was recurrence of the scleral thickening and contrast enhancement in the right eye (arrow), as well as thickening and enhancement of the right optic nerve sheath (arrowhead). No abnormalities were observed in the extraocular muscles.

Laboratory tests revealed an elevated C-reactive protein level of 1.31 mg/dL (reference range, 0–0.3) and erythrocyte sedimentation rate of 36 mm/1 h (reference range, 2–10). Tests for rheumatoid factor, anticyclic citrullinated peptide antibodies, proteinase 3-anti-neutrophil cytoplasmic antibody, myeloperoxidase-anti-neutrophil cytoplasmic antibody, interferon-gamma release assay, and syphilis were negative. The serum angiotensin-converting enzyme was low at 6.8 IU/L (reference range, 8.3–21.4 IU/L), while serum IgG4 was normal at 36 mg/dL (reference range, 11–121 mg/dL). The TSH receptor antibody (TRAb) test was negative, and the levels of free tri-iodothyronine and free thyroxine were within the normal range. Workup done by rheumatology revealed no findings of joint swelling or tenderness, temporal artery abnormalities, salivary gland enlargement, saddle-nose deformity, auricular chondritis, or lateralized hearing loss. Thus, the patient was diagnosed with idiopathic orbital inflammation accompanied by posterior scleritis, optic perineuritis, and ocular motility disorder.

Oral steroid therapy with prednisolone (50 mg/day) was initiated 2 days after the initial visit, which improved the posterior scleritis, anterior chamber inflammation, and ocular motility disorder. On MRI, there was improvement of optic perineuritis in the right eye (shown in Fig. 4b). Optical coherence tomography demonstrated resolution of the choroidal folds, normalization of choroidal thickness, and complete disappearance of the subretinal fluid (shown in Fig. 2b). The myopic shift also resolved, and the visual acuity improved to 20/17 in the right eye without correction. The visual field defect in the right eye was no longer detectable. The prednisone was tapered to 10 mg/day over 4.5 months, but the scleritis, ocular motility disorder, and optic perineuritis recurred (shown in Fig. 3b, 4c). Therefore, the dose was increased back to 30 mg/day, which improved these ocular symptoms. Given the clinical course, administration of a steroid-sparing agent was considered necessary. Under the national health insurance system in Japan, only two agents – adalimumab and cyclosporine – are approved for use as steroid-sparing agents in idiopathic sclerouveitis. Therefore, adalimumab was initiated in combination with prednisolone at a dose of 15 mg/day. Adalimumab was continued while tapering prednisolone to 4 mg/day without recurrence of ocular symptoms. Afterward, 22 months after the initial treatment, oral prednisolone (4 mg/day) was shifted to oral hydrocortisone (15 mg/day) due to secondary adrenal insufficiency. Six months since discontinuing prednisolone, oral hydrocortisone dose had also been reduced to 10 mg/day, the disease remained in remission, including the ocular motility disorder (shown in Fig. 3c) and optical coherence tomography findings (shown in Fig. 2c). At the final visit, the right eye had a visual acuity of 20/17 without correction and a CFF of 38.8 Hz, respectively.

Discussion

Idiopathic orbital inflammation is a benign, nonspecific inflammatory disorder that commonly occurs in middle-aged adults and is usually unilateral [2]. Its clinical manifestations are greatly heterogenous, varying according to the site of infiltration and the degree of lesions, including orbital pain, swelling/mass, erythema, diplopia, proptosis, limited ocular motility, decreased vision, optic neuropathy, conjunctival congestion, and ptosis [2]. Accordingly, various classifications of idiopathic orbital inflammation have been reported. Yamagami et al. [3] classified idiopathic orbital inflammation into the following patterns: extraocular myositis, dacryoadenitis, optic perineuritis, intraorbital diffuse inflammation, tenonitis/scleritis, and orbital apex inflammation. Among these, tenonitis/scleritis and optic perineuritis predominantly overlapped with other types in 83%–90% of cases [3]. Fang et al. [2] also classified idiopathic orbital inflammation into four types based on anatomical location: lacrimal gland, sclera and adjacent tissues, extraocular muscles, and optic nerve sheath.

This case presented with both posterior scleritis and ocular motility disorders without extraocular myositis, and MRI also revealed optic perineuritis. The observed myopic shift and anterior chamber shallowing are presumed to be secondary to ciliochoroidal detachment or effusion, which might have resulted in forward displacement of the iris-lens diaphragm and inward rotation of the ciliary body. There was no identifiable underlying disease upon systemic evaluation. Thus, the patient was diagnosed with idiopathic orbital inflammation complicated by posterior scleritis and optic neuritis. Since there was no enlargement or inflammation of the extraocular muscles on MRI, the ocular motility disorder was deemed to be associated with inflammation of the orbital tissues.

Most cases of idiopathic orbital inflammation respond to traditional therapies such as glucocorticoids, radiation therapy, and immunosuppressive agents, which are the mainstay of treatment [2, 7]. However, despite it being the first-line treatment, 52% of patients treated with systemic glucocorticoids experience relapse after an initial dramatic improvement [7]. Emerging evidence has described the efficacy of biological agents for idiopathic orbital inflammation, positioning them as a potential therapeutic option for cases that are refractory to or relapse after conventional treatment [2, 7]. As TNF-α levels are significantly elevated in orbital biopsy specimens from patients with idiopathic orbital inflammation compared with those in controls [8], TNF inhibitors represent therapeutic options for idiopathic orbital inflammation in patients who are refractory to corticosteroids or those who experience relapse after corticosteroid therapy. In particular, infliximab has displayed great potential for treating idiopathic orbital inflammation [9, 10], whereas evidence regarding the efficacy of adalimumab remains comparatively limited. One report described two cases of orbital myositis in which improvements in swelling, pain, and diplopia, as well as decreased steroid dependency, were achieved with the use of adalimumab [11]. By contrast, TNF-α is one of the key inflammatory mediators in scleritis [12], and a number of studies have demonstrated the anti-inflammatory and glucocorticoid-sparing effects of adalimumab in its treatment [13]. Furthermore, a previous study reported that adalimumab combined with conventional therapy, defined as the use of systemic glucocorticoids and other immunosuppressants, shortened the time to remission, reduced disease flares, and facilitated glucocorticoid tapering compared with the effects of conventional therapy alone in patients with refractory noninfectious scleritis [14]. In the present case, posterior scleritis, optic perineuritis, and ocular motility disorder recurred after tapering the prednisolone dose to 10 mg/day, which prompted the introduction of adalimumab as a steroid-sparing agent. Since starting adalimumab, the patient’s ocular symptoms have not recurred, and prednisolone was successfully discontinued. She has since been maintained on adalimumab and oral hydrocortisone for secondary adrenal insufficiency. Considering that a 10 mg dose of oral hydrocortisone is approximately equivalent to 2.5 mg of prednisolone and that disease relapse had previously occurred when the patient was treated with prednisolone 10 mg/day, these findings suggest that adalimumab contributed to maintaining remission through its glucocorticoid-sparing and anti-relapse effects on idiopathic orbital inflammation. Although these findings are promising, further accumulation of case reports is needed to evaluate the efficacy of adalimumab in idiopathic orbital inflammation. There is currently no established consensus on the optimal duration of adalimumab therapy in scleritis or idiopathic orbital inflammation. According to a large real-world cohort study of patients with noninfectious uveitis conducted by Eurelings et al. [15], adalimumab therapy was continued for a median of 3.2 years before discontinuation. Of the 57 patients who discontinued the therapy after achieving inactive disease, 37 (65%) relapsed; of them, 31 restarted adalimumab, and disease inactivity was subsequently restored in 23 (74%) patients. Based on these findings, we plan to continue adalimumab for approximately 3 years in our patient alongside careful monitoring of disease activity. If remission is maintained for a sufficient period, then discontinuation will be considered, followed by close observation for potential relapse.

In conclusion, this report describes a rare case of idiopathic orbital inflammation with posterior scleritis, complicated by optic perineuritis and ocular motility disorder. Although the condition relapsed after steroid tapering, this was subsequently well controlled with the initiation of adalimumab. Thus, adalimumab may be effective in preventing recurrence in this subtype of idiopathic orbital inflammation.

Statement of Ethics

This study was approved by the Research Ethics Committee of the Graduate School of Medicine and Faculty of Medicine at The University of Tokyo, Approval No. 2217. Written informed consent was obtained from the patient for publication of the details of this medical case and any accompanying images. The CARE Checklist has been completed by the authors for this case report and has been provided as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000549539).

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was not supported by any sponsor or funder.

Author Contributions

Yuka Numaga: writing – original draft. Yurika Aoyama: investigation and writing – review and editing. Rie Tanaka: conceptualization, investigation, writing – review and editing, and supervision.

Funding Statement

This study was not supported by any sponsor or funder.

Data Availability Statement

All data analyzed during this study are included in this article and its supplementary material files. Further inquiries can be directed to the corresponding author.