Cutting-edge issues in sympathetic ophthalmia approach and six case reports: a T cell-mediated autoimmune response.

Sympathetic ophthalmia is a rare and potentially devastating bilateral diffuse granulomatous panuveitis. It is caused by surgical or non-surgical eye injuries and is an uncommon and serious complication of trauma. It is diagnosed clinically and supported by imaging examinations such as ocular ultrasonography and optical coherence tomography. Its treatment consists of immunosuppressive therapy with steroids and sometimes steroid-sparing drugs, such as cyclosporine, azathioprine, cyclophosphamide, and mycophenolate mofetil. Fast and effective management with systemic immunosuppressive agents allows for disease control and achievement of good visual acuity in the sympathizing eye. By contrast, enucleation should be considered only in situations where the injured eye has no light perception or in the presence of severe trauma. In addition to a bibliographic review of this topic, we report six cases involving different immunosuppressive and surgical treatment modalities.

Vision Outcomes of Long-Term Immunomodulatory and Steroid Therapy in Sympathetic Ophthalmia.

PURPOSE: To compare vision acuity outcomes of long-term steroid therapy compared with immunomodulatory therapy for treatment of sympathetic ophthalmia. DESIGN: Single-center, retrospective, comparative clinical study. METHODS: Patients with sympathetic ophthalmia treated from March 2005 to October 2022 with at least 1 year of follow-up were included. Visual acuity outcomes were compared by steroid and immunomodulatory treatment modality. RESULTS: Thirty-five patients with sympathetic ophthalmia were included in the study, with follow-up ranging from 1 to 17 years. Higher rates of vision loss correlated with longer periods of active uveitis and steroid treatment. Lower rates of vision loss correlated with longer periods of uveitis remission on immunomodulatory therapy alone and drug-free remission. Treatment with alkylating agents or combination therapy with an antimetabolite, a biologic-response modifier, and cyclosporine are more likely to result in sympathetic ophthalmia remission. CONCLUSION: Immunomodulatory therapy leads to superior vision outcomes in cases of steroid-resistant or recurrent sympathetic ophthalmia. Steroid therapy may be useful for acute or recalcitrant sympathetic uveitis but is insufficient for long-term inflammatory control. PRéCIS: This manuscript describes a retrospective analysis of vision outcomes in patients with sympathetic ophthalmia. Results indicate that long-term immunomodulatory therapy is associated with better vision outcomes than long-term steroid therapy for sympathetic ophthalmia treatment.

Leopard retinopathy: An unusual presentation of sympathetic ophthalmia.

We report an unusual case of sympathetic ophthalmia (SO) in an elderly gentleman following multiple eye surgeries. He presented with diffuse granulomatous panuveitis resembling leopard retinopathy in the left eye. There was a delay in the initiation of effective treatment of his intraocular inflammation, but he responded to corticosteroid and azathioprine. The pigmentary changes in his fundus were highly unusual, and he was investigated extensively to rule out other possible causes including a search for occult malignancy. The delay in initiation of effective treatment or suboptimal therapy in SO, can lead to variable clinical picture in elderly patients. A proper screening to exclude any malignancy along with aggressive immunosuppressive therapy can achieve optimum results.

Sympathetic ophthalmia: A comprehensive update.

Sympathetic ophthalmia is a rare, bilateral, granulomatous, panuveitis following penetrating trauma or surgery to one eye. Clinical presentation commonly occurs within the first year of trauma occurrence but can be delayed by several years. It manifests as acute/chronic granulomatous uveitis with yellowish-white choroidal lesions or Dalen-Fuchs nodules. Initially, patients respond rapidly to corticosteroid therapy, but a majority require long-term use of corticosteroid-sparing agents to prevent recurrences. The purpose of this review is to elaborate on the current understanding of the pathophysiology, the importance of multimodal imaging in early diagnosis, and the role of newer immunomodulatory and biological agents in recalcitrant cases.

Clinical and imaging features of sympathetic ophthalmia and efficacy of the current therapy.

PURPOSE: The purpose of the study was to clarify the clinical and imaging features of sympathetic ophthalmia (SO) and evaluate the efficacy of the current therapy. METHODS: The databases PubMed, EMBASE and Ovid up to January 2021 were searched to identify relevant studies. R software version 3.6.3 was used to perform the statistical analyses. RESULTS: Thirty-two studies involving 1067 patients were finally included. Our study found SO was male-dominated, and more than half of SO patients aged 16 to 60 years old. Ocular trauma, surgical interventions and unknown events were estimated to be inciting events in 63%, 36% and 4% of SO patients. About 35% of the patients underwent baseline enucleation, and 45% took compelled enucleation during follow-up. The most common symptoms at the first presentation were decreased vision, followed by pain and redness. The most common signs were anterior chamber cells/flare, followed by vitritis, exudative retinal detachment and Dalen-Fuch nodules. Choroidal thickening was detected in 81% of SO patients by ocular ultrasound. The most common fluorescein fundus angiography signs were disc leakage. After corticosteroid therapy became the mainstay for SO, about 76% of SO patients could get inflammation well-controlled, while 24% of them might have recurrent inflammation. Around 72% of SO patients could achieve visual improvement, and more than half of them might have a best-corrected visual acuity of 20/50 or better. CONCLUSION: SO is a complicated ocular disease with diverse clinical manifestations and imaging features. After proper anti-inflammation therapy, SO might not necessarily result in a poor prognosis.

Atypical Sympathetic Ophthalmia Presenting with Ocular Pain Associated with Posterior Scleral Involvement.

PURPOSE: To describe an atypical case of sympathetic ophthalmia. Design: Case report. RESULTS: A 37 -year-old female presented a 3-day long acute left retroocular pain and photophobia, 1 month after having undergone evisceration of the fellow eye. Upon exploration, the patient presented conjunctival injection, macular retinal folds with peripapillary subretinal fluid, and hypocyanescent choroidal spots on indocyanine green angiography. A sympathetic ophthalmia with a reactive posterior scleritis involvement was diagnosed. The patient underwent treatment with prednisone, mycophenolate, and cyclosporine with slowly tapering, presenting a total recovery over the years. CONCLUSION: Sympathetic ophthalmia may present itself atypically as ocular pain with little vision loss secondarily to a mild panuveitis with reactive scleral involvement.

Incidence of Sympathetic Ophthalmia after Inciting Events: A National Database Study in Japan.

PURPOSE: To analyze the incidence of sympathetic ophthalmia (SO) after inciting events (eye trauma or intraocular surgery). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients experiencing inciting events between 2012 and 2019. Onset of SO was defined as the first date of SO diagnosis. METHODS: Using a nationwide administrative claims database in Japan, we calculated the cumulative incidence of SO after inciting events stratified by sex, 10-year age groups, and a categorical variable of primary or repeated, reflecting the history of inciting events in the past year (no inciting events, inciting events without trauma, or inciting events with trauma) using the Kaplan-Meier approach. We also estimated the adjusted hazard ratio (aHR) by Cox regression. We then restricted the population to those with only 1 inciting event during the observation period to investigate the pure effect of each inciting event. MAIN OUTCOME MEASURES: Cumulative incidence of SO over 60 months. RESULTS: A total of 888 041 inciting events (704 717 patients) were eligible. The total number of SO cases was 263, and the cumulative incidence of SO was 0.044% over 60 months. Female sex was not associated with onset of SO (aHR, 1.01; 95% confidence interval [CI], 0.79-1.29; P = 0.95). The group 40 to 49 years of age showed the highest incidence of 0.104% among the age groups (aHR vs. ≥80 years of age group [0.041%], 2.44 [95% CI, 1.56-3.80]; P < 0.001). Repeated inciting events with and without trauma showed higher incidences of SO (0.469% and 0.072%, respectively) than primary inciting events (0.036%) (aHR 11.68 [7.74-17.64] and 2.21 [95% CI, 1.59-3.07], respectively); P < 0.001 and P < 0.001, respectively). The incidence of SO after vitrectomy was much lower than after trauma (0.016% vs. 0.073%), and the incidence after scleral buckling was even lower. CONCLUSIONS: The cumulative incidence of SO over 60 months was estimated to be 0.044% at minimum. Repeated inciting events, especially those with trauma, increased the risk of SO developing. Trauma was 4 to 5 times as likely to induce SO than vitrectomy. The present findings will be valuable for counseling patients about the risks of SO after trauma and before performing intraocular surgeries.

Sympathetic ophthalmia after vitreoretinal surgery: a report of two cases.

Sympathetic ophthalmia (SO) is a panuveitis that usually occurs after trauma to one eye. We describe two cases of SO occurring after 23-gauge vitrectomy. Case 1 involved a 66-year-old woman who underwent pars plana vitrectomy (PPV) for a rhegmatogenous retinal detachment. Two months later, she presented with decreased visual acuity (VA) and bilateral uveitis. Case 2 involved a 43-year-old woman who underwent a second PPV for recurrent retinal detachment. Two months later, she presented with bilateral panuveitis. Both patients were diagnosed with SO and were treated with methylprednisolone and cyclosporine. The first patient was further treated with a dexamethasone intravitreal implant (Ozurdex®) owing to the side effects of methylprednisolone. The VA and symptoms improved significantly after treatment in both patients. Bilateral granulomatous panuveitis following PPV should alert surgeons to consider SO. Appropriate interventions for SO can produce positive outcomes.

Sympathetic ophthalmia following blunt injury to phthisical eye.

Sympathetic ophthalmia is a severe sight-threatening disorder that can lead to blindness if not diagnosed and managed appropriately. It occurs most commonly following penetrating ocular injury and less commonly following surgery. Herein, we report a case of sympathetic ophthalmia following blunt trauma to the phthisical eye along with the pathophysiology and management of such cases.

Celastrol Regulates the Secretion of Interleukin-17 in Patients with Sympathetic Ophthalmia Through Signal Transducer and Activator of Transcription 3.

Purpose: The excessive secretion of interleukin (IL)-17 contributes to the pathological process of sympathetic ophthalmia (SO). Celastrol is a naturally active product and exhibits an immunosuppressive effect. However, whether the supplementation of celastrol relieves SO remains unclear. Methods: The peripheral blood mononuclear cells (PBMCs) were extracted from the venous blood samples of 20 SO patients and 20 healthy controls, followed by stimulating with various concentrations of celastrol. The levels of IL-23 and IL-17 were measured by enzyme-linked immunosorbent assay and real-time polymerase chain reaction assay. The activation of the signal transducer and activator of transcription 3 (STAT3) in PBMCs of SO patients was detected by Western blot. Results: The levels of IL-23 and IL-17 in PBMCs isolated from SO patients were significantly increased compared with those in PBMCs isolated from healthy controls. Celastrol treatment inhibited the production of both IL-23 and IL-17 in PBMCs of SO patients in a dose-dependent manner. In PBMCs isolated from SO patients and healthy controls, the administration of recombinant human IL-23 (rIL-23) enhanced the production of IL-17, which was then suppressed by co-stimulation with celastrol. Also, celastrol treatment reduced rIL-23-induced phosphorylation of STAT3 in PBMCs isolated from SO patients. Conclusions: Celastrol can reduce the production of IL-17 in PBMCs of SO patients. The mechanism may be related to the reduction of IL-23 secretion, which in turn inhibits the phosphorylation of STAT3.

Pediatric Sympathetic Ophthalmia: 20 Years of Data From a Tertiary Eye Center in India.

PURPOSE: To examine the clinical profile of sympathetic ophthalmia among the pediatric age group. METHODS: Retrospective review of patients 18 years and younger with sympathetic ophthalmia seen in a tertiary eye care center between 1997 and 2017. RESULTS: Of 20 patients included in the study, 70% were male. The most common inciting event for sympathetic ophthalmia was trauma (85%), followed by vitreoretinal surgery (15%). All patients were treated with systemic steroids. Seventeen patients received additional corticosteroid-sparing immunosuppressive agents, and 4 patients (20%) required more than one immunosuppressive agent. Azathioprine was the most commonly used corticosteroid-sparing immunosuppressive agent. The most common complications were cataract (50%) and ocular hypertension (30%). The mean presenting best corrected visual acuity in the sympathizing eye was 1.15 ± 0.99 logarithm of the minimum angle of resolution (logMAR), which improved to 0.54 ± 1.00 logMAR following treatment. Visual outcome was good (6/12 or better) in 70% of the sympathizing eyes, and 3 of the exciting eyes in the current study had good visual outcomes after the treatment. CONCLUSIONS: Prompt and effective management with corticosteroid-sparing immunosuppressive therapy in children with sympathetic ophthalmia allows favorable control of the disease and retention of good visual acuity. [J Pediatr Ophthalmol Strabismus. 2020;57(3):154-158.].

Sympathetic Ophthalmitis: A Rare Case Report.

Sympathetic ophthalmitis (SO) is defined as bilateral granulomatous panuveitis occurring after penetrating ocular trauma or intraocular surgery. It is now rare due to micro-surgical repair of ocular injury and use of steroid. An 18 years old boy admitted into Ophthalmology department of Mymensingh Medical College Hospital, Mymensingh, Bangladesh on 2nd March 2018. He got penetrating corneal injury in R/E with sharp pointed object 01 month back. It was conservatively managed but his right eye became phthisical. After 04 weeks his left eye was affected in which VA became 3/60, features of panuveitis developed. It was managed with high dose steroid and immunomodulatory drug (Azathioprine). Ultimately his vision of left eye is fully preserved (6/6). So, after a trauma or surgery to one eye, another eye should be meticulously examined and followed up. Early diagnosis and prompt treatment of Sympathetic Ophthalmitis may prevent from blindness.

Progressive, subretinal fibrosis mimicking retinal necrosis with poor visual prognosis in sympathetic ophthalmia: A rare finding.

We report a rare finding of progressive subretinal fibrosis mimicking retinal necrosis in 2 cases of sympathetic ophthalmia. Histopathology of the inciting eye and vitreous biopsy of the sympathizing eye ruled out infections and masquerades. Progression of inflammation and rapid deterioration of vision inspite of maximum immunosuppression are key findings in this variant of sympathetic ophthalmia.

Oftalmia simpática / Sympathetic ophthalmia

Resumo Relatar um caso de um paciente portador de Oftalmia Simpática (OS), com descolamento seroso da retina documentado através de tomografia de coerência óptica de domínio spectral (SD OCT), indocianina verde (ICG) e angiofluoreceinografia (AGF), que o diagnóstico foi realizado em uma consulta de rotina e iniciado tratamento clínico .

Abstract To report the case of a patient with sympathetic ophthalmia (OS), with serous detachment of retinal documented by spectral domain optical coherence tomography (OCT), indocyanine green (ICG) and angiofluorecephography (AGF). The diagnosis was made in a routine consultation and clinical treatment was initiated.

Treatment Response in Sympathetic Ophthalmia as Assessed by Widefield OCT Angiography.

The authors report the widefield montage swept-source optical coherence tomography angiography (OCTA) findings in a 36-year-old male with sympathetic ophthalmia and illustrate the presence of multiple small areas of choriocapillaris flow voids that likely correspond to areas of choriocapillaris ischemia. Using sequential imaging, the authors observed that these flow voids improved following initiating of steroid and immunosuppressive therapy and almost completely resolved following 6 months of therapy with corresponding improvement in visual acuity. This report highlights the role of widefield montage OCTA to detect these likely ischemic changes within the choriocapillaris in sympathetic ophthalmia and demonstrates that they can be used as an anatomic marker to monitor treatment response. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:726-730.].

2-Methoxyestradiol Alleviates Experimental Autoimmune Uveitis by Inhibiting Lymphocytes Proliferation and T Cell Differentiation.

Purpose. To investigate the effect of 2-Methoxyestradiol (2ME2) on experimental autoimmune uveitis (EAU) and the mechanism. Method. C57BL/6 male mice were used to establish the EAU model. 2ME2 was abdominal administrated in D0-D13, D0-D6, and D7-D13 and control group was given vehicle from D0-D13. At D14, pathological severity was scored. Lymphocyte reaction was measured using MTT assay. T cell differentiation in draining lymph nodes and eye-infiltrating cells was tested by flow cytometry. Proinflammatory cytokines production from lymphocytes was determined by ELISA. Result. The disease scores from 2ME2 D0-D13, 2ME2 D0-D6, 2ME2 D7-D13, and vehicle groups were 0.20 ± 0.12, 1.42 ± 0.24, 2.25 ± 0.32, and 2.42 ± 0.24. Cells from all 2ME2 treated groups responded weaker than control (p < 0.05). The inhibitory effect of 2ME2 on lymphocyte proliferation attenuated from 2ME2 D0-D13 to 2ME2 D0-D6 and to 2ME2 D7-D13 groups (p < 0.05). 2ME2 treated mice developed fewer Th1 and Th17 cells both in draining lymph nodes and in eyes than control (p < 0.05). Lymphocytes from 2ME2 group secreted less IFN-γ and IL-17A than those from control (p < 0.05). Conclusion. 2ME2 ameliorated EAU progression and presented a better effect at priming phase. The possible mechanism could be the inhibitory impact on IRBP specific lymphocyte proliferation and Th1 and Th17 cell differentiation.

Sympathetic ophthalmia following a conjunctival flap procedure for corneal perforation.

A 25-year-old man developed diminution of vision and redness in both eyes 5 weeks after a conjunctival flap procedure in the right eye. On examination, there was panuveitis and exudative retinal detachment in both eyes. The right eye had an inferotemporal conjunctival flap with iris incarceration. Fundus fluorescein angiography revealed typical pinpoint leaks and optical coherence tomography demonstrated multiple neurosensory detachments in the left eye. The patient received frequent topical steroids and cycloplegics. Intravenous dexamethasone pulse was given followed by high-dose oral prednisone, after which the patient recovered vision. The conjunctival flap in corneal perforation may predispose to sympathetic ophthalmia.

[Sympathetic ophthalmia : Therapy with steroid-free immunosuppressant azathioprine]. / Sympathische Ophthalmie : Therapie mit steroidsparendem Immunsuppressivum Azathioprin.

This article describes the case of a 48-year-old male patient who presented with persistent inflammation and deterioration of vision to a best corrected visual acuity (BCVA) of 0.6 in the only functioning left eye. The right eye had suffered a severe penetrating ocular trauma 6 months prior to presentation. After diagnosis of a sympathetic ophthalmia a high dosage corticosteroid therapy was initiated. Due to intolerance with decompensating diabetes an immunosuppressive therapy with azathioprine was initiated. This therapy resulted in stable clinical findings with an increase in BCVA to 0.9.