The Epidemiology and Risk Factors for the Progression of Sympathetic Ophthalmia in the United States: An IRIS Registry Analysis.

PURPOSE: To investigate the demographic and clinical characteristics of patients with sympathetic ophthalmia (SO) and define the risk factors for its incidence following trauma and ophthalmic procedures. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients in the American Academy of Ophthalmology's (Academy) IRIS Registry (Intelligent Research in Sight) who were (n=1523) or were not diagnosed with SO following a documented procedure or trauma between January 1, 2013, and December 31, 2019. METHODS: Multiple demographic and clinical factors were collected, descriptive statistics and prevalence were calculated, and multivariate linear regression models were fit to the data. MAIN OUTCOME MEASURES: Prevalence of SO, demographic and clinical characteristics, and beta coefficient (ß) estimates of demographic and clinical characteristics impacting time to SO onset after procedure (Procedure Only cohort) or trauma (Trauma cohort). RESULTS: Of 65,348,409 distinct IRIS Registry patients, 1523 (0.0023%) were diagnosed with SO between 2013 and 2019, and also had a documented preceding trauma or procedure. Of these, 927 (60.87%) were female, 1336 (87.72%) belonged to the Procedure Only cohort, and 187 (12.28%) belonged to the Trauma cohort. The prevalence of SO after trauma was 0.0207%, whereas after procedures it was 0.0124%. The highest risk of procedure-related SO was seen in patients with history of "other anterior segment" (0.122%) followed by glaucoma (0.066%) procedures, whereas the lowest prevalence was noted with cataract surgeries (0.011%). The average time to onset of SO across both cohorts combined was 527.44 (±715.60) days, with statistically significant differences between the 2 cohorts (P < .001). On average, the time to onset from inciting event to SO was shorter with increasing age, by 9.02 (95% CI: -11.96, -6.08) days for every 1-year increase. CONCLUSIONS: SO following trauma and ophthalmic procedure is potentially rarer than previously reported, as measured in this large ophthalmic medical record database. Female sex may be a risk factor for SO. Older age may be a risk factor for quicker onset. These findings can guide clinical decision-making and management.

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.

Sympathetic ophthalmia in an 85-year-old female and a 90-year-old male after a non-complicated cataract surgery: a case report.

Here, two cases involving the oldest reported patients with sympathetic ophthalmia (SO) after non-complicated cataract surgery, are reported. The first case was an 85-year-old female with bilateral decreased vision and headache. The best-corrected visual acuity (BCVA) was 0.8 in the right eye and 1.0 in the left eye at the initial visit. Pseudophakia and choroidal detachments were observed in both eyes, and retinal pigment epithelium undulation was observed by optical coherence tomography. The second case was a 90-year-old male with bilateral optic disc oedema. The BCVA was 0.09 in the right eye and 0.3 in the left eye with pseudophakic eyes. Optic disc oedema and choroidal thickening were observed in both eyes. Both patients were diagnosed with SO, and corticosteroid pulse treatments were started. The BCVA of the first case improved to 0.9 in the right eye and 1.2 in the left eye, while that of the second case reached 0.3 in the right eye and 0.6 in the left eye. No recurrence was observed in either case at 12 months after the initial visit. Both elderly patients with SO were successfully treated.

Sympathetic Ophthalmia: Demographic Characteristics, Clinical Findings, and Treatment Results.

Objectives: To evaluate the demographic characteristics, clinical findings, and treatment approach of patients with sympathetic ophthalmia (SO). Materials and Methods: The records of 14 patients with SO between 2000 and 2020 were retrospectively reviewed. The patients' Snellen best corrected visual acuity (BCVA), detailed ophthalmological examination, optical coherence tomography (OCT), enhanced depth imaging-OCT (EDI-OCT), fundus fluorescein angiography findings, and treatment approaches were recorded. Results: The study included the 14 sympathizing eyes of 14 patients with SO (7 female, 7 male). The mean age was 48.5±15.4 years (range: 28-75), and the mean follow-up duration was 55.1±48.7 months (range: 6-204). Ten patients (71%) had a history of ocular trauma and 4 (29%) had a history of ocular surgery. The time to symptom onset in the sympathizing eye after trauma or ocular surgery ranged from 15 days to 60 years. The most common posterior segment findings were optic disc edema (36%) and exudative retinal detachment (36%). In the acute period, the mean choroidal thickness value on EDI-OCT was 716.5±63.6 µm (range: 635-772) and decreased to 296±81.6 µm (range: 240-415) after treatment. Treatment with high-dose systemic corticosteroid was given to 8 patients (57%), azathioprine (AZA) to 7 (50%), AZA and cyclosporine-A combination to 7 (50%), and tumor necrosis factor-alpha inhibitors to 3 patients (21%). Recurrence was observed in 4 patients (29%) during follow-up. At last follow-up, BCVA values were better than 20/50 in 11 (79%) of the sympathizing eyes. Remission was achieved in 13 patients (93%), but 1 patient (7%) lost her vision due to acute retinal necrosis. Conclusion: SO is a bilateral inflammatory disease that presents with granulomatous panuveitis after ocular trauma or surgery. Favorable functional and anatomical results can be obtained with early diagnosis and initiation of appropriate treatment.

Sympathetic Ophthalmia - An Overview.

INTRODUCTION: Sympathetic ophthalmia (SO) is rare, bilateral granulomatous panuveitis that typically occurs following penetrating or perforating ocular trauma or surgery. This review aims to provide an update on the etiopathogenesis, clinical presentations, diagnosis and treatment of SO. METHODS: Reports cited in MEDLINE database, that analyzed SO in at least 5 patients, published prior to December 1st, 2021 were included. RESULTS: Initially, SO was associated with penetrating ocular trauma, however, various studies reported an increased incidence of SO after surgical procedures including vitreoretinal surgeries. Multimodal imaging including fluorescein and indocyanine green angiography, optical coherence tomography (OCT) and OCT angiography have added further insights into the understanding of SO. While pulse dose corticosteroids & immunosuppressive drugs are still the treatment of choice, TNF-α blockers & other biologic drugs represent new promising agents. CONCLUSION: There is a growing pool of evidence in understanding the pathogenesis of SO. Novel treatment options have provided better prognosis for this potentially blinding condition.

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.

Sympathetic Ophthalmia - case report.

Purpose. To present the case of a 22-year-old man with a history of trauma on the right eye, followed by a sudden decrease of visual acuity on the left eye, but with a good recovery after surgical treatment. Material and methods. We reported a case of a 22-year-old patient with a sudden and painless decrease of visual acuity on the left eye, a month after a car accident, which led to the laceration of the right globe. At first, the patient received only medical treatment because he refused any surgical intervention. He had a favorable evolution during hospitalization, but he returned after a month with the same visual acuity as at his first admission. The patient accepted the medical treatment and the enucleation of the right eye, thus having a fast improvement in his visual acuity on the left eye. Conclusions. Although the enucleation was overdue, it had a strong favorable influence on the evolution of the disease. As a result of the surgery, the visual acuity has improved significantly in just a few days. Abbreviations: OCT = optical coherence tomography.

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.

The Risk of Sympathetic Ophthalmia after Vitreoretinal Surgery.

PURPOSE: To investigate the clinical course and outcomes of sympathetic ophthalmia (SO) and correlate these with the nature of the inciting event and the number of vitreoretinal (VR) procedures undergone by patients. DESIGN: A retrospective case review. SUBJECTS: All patients diagnosed with SO who had been treated or monitored at a single center over a 15-year period. METHODS: A search of the electronic patient record system at Moorfields Eye Hospital, London, over a 15-year period (between January 2000 and December 2015) was carried out using the search terms "sympathetic," "ophthalmia," and "ophthalmitis." Sixty-one patients with available records were identified, and data were collected from their complete electronic and paper records. MAIN OUTCOME MEASURES: The main outcome measures were best-corrected visual acuity at 1 year and at the end of follow-up and the number of VR surgical procedures preceding the diagnosis of SO. Data on patient age, sex, disease duration, ocular and systemic manifestations, ocular complications, retinal angiography, and treatment were also collected. RESULTS: There was a wide age range at presentation (2-84 years), and the length of follow-up ranged from 1 to 75 years. The first ocular event was trauma in 40 patients and surgery in 21 patients. Vitreoretinal surgery accounted for 13 of the 21 (62%) surgical first-event triggers. Twenty-three of 61 (38%) patients underwent VR surgery (1-7 operations) at some point before diagnosis. Surgical details were available for 15 patients, who had undergone a total of 25 VR procedures. Based on the surgical activity of the unit, the risk of developing SO after a single VR procedure was estimated to be 0.008%, rising to 6.67% with 7 procedures. A total of 23 (38%) patients experienced a decrease in acuity at the end of the follow-up period, vs. 9 (15%) patients experiencing an improvement and 18 (30%) remaining unchanged. CONCLUSIONS: We feel that the most significant finding in this study is the calculated risk of SO development after a single VR procedure, which was significantly lower in our cohort than that previously reported in the literature. This was seen to rise exponentially with additional procedures.

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.

The Incidence of Sympathetic Ophthalmia After Trauma: A Meta-analysis.

PURPOSE: Sympathetic ophthalmia (SO) is a rare, bilateral panuveitis that occurs following open globe injury (OGI), with a variable incidence reported in the literature. Our objective was to determine the incidence proportion and incidence rate of SO following OGI to help guide shared physician-patient decision making. DESIGN: Systematic review and meta-analysis. METHODS: A systematic literature search was performed using the MEDLINE, EMBASE, and Cochrane databases from inception to November 2020 for population-based studies on OGI and SO in adults and children. Two reviewers independently screened search results. Random-effects meta-analyses were performed to calculate the incidence proportion and incidence rate. The Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) tool was used to assess the risk of bias. The study was registered on PROSPERO CRD42020198920. RESULTS: A total of 24 studies were utilized in the meta-analyses. After OGI, the estimated overall incidence proportion of SO was 0.19% (95% CI 0.14%-0.24%) and the incidence rate of SO was 33 per 100,000 person-years, (95% CI 19.61-56.64) with I2 of 13% and 72%, respectively. CONCLUSIONS: SO after OGI is rare. The estimated incidence proportion and incidence rate are useful when counselling patients regarding management options after OGI. Further studies are needed to examine the influence of age, the extent and location of trauma, timing of repair, and prophylactic eye removal on the incidence of SO.

The Ruptured Globe, Sympathetic Ophthalmia, and the 14-Day Rule.

PURPOSE: Prophylactic enucleation of a ruptured globe with no light perception within 14 days of injury to prevent sympathetic ophthalmia (SO) has been an established dictum in academic teaching for more than 100 years. This treatment strategy was originally based on observation, speculation, and careful thought, but there was never any scientific proof. This review summarizes and updates the current state of our knowledge about globe rupture and SO, examines the origin and validity of the 14-day rule, and emphasizes the importance of trying to save the traumatized eye whenever possible. METHODS: A comprehensive literature review of SO and globe rupture was performed. RESULTS: SO is a rare disorder that may potentially occur following traumatic globe rupture as well as following a variety of other intraocular surgeries. Vitreoretinal surgery may be a more common cause than trauma according to some studies. SO may still occur despite having the eye removed within 14 days of the trauma. A variety of new medications including biologic agents are now available to treat SO with improved efficacy in suppressing the associated ocular inflammation and allowing retention of some useful vision. Removing the traumatized, blind eye may have other important psychological consequences associated with it that require consideration before eye removal is carried out. Retaining the blind, phthisical, disfigured eye avoids phantom vision and phantom pain associated with enucleation as well as providing a good platform to support and move an overlying prosthetic eye. Data on the occurrence of SO following evisceration and enucleation with and without predisposing factors confirms the exceedingly low risk. CONCLUSION: Most civilian open globe injuries can be successfully repaired with modern, advanced microsurgical techniques currently available. Because of the exceedingly low risk of SO, even with the severity of open globe trauma during military conflicts being more devastating as a result of the blast and explosive injuries, today every attempt is made to primarily close the eye rather than primarily enucleate it, providing there is enough viable tissue to repair. The 14-day rule for eye removal after severe globe ruptures is not scientifically supported and does not always protect against SO, but the safe time period for prophylactic eye removal is not definitively known. In the exceptional cases where SO does occur, several new medications are now available that may help treat SO. We advocate saving the ruptured globe whenever possible and avoiding prophylactic enucleation to prevent the rare occurrence of SO. When an eye requires removal, evisceration is an acceptable alternative to enucleation in cases that do not harbor intraocular malignancy.

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.

Recent advances in diagnosis and management of sympathetic ophthalmia.

PURPOSE OF REVIEW: Sympathetic ophthalmia is a bilateral granulomatous uveitis that occurs following unilateral trauma or surgery and is sight-threatening in the contralateral eye. Despite significant potential morbidity, disease remains poorly understood. Variable presentations and clinical courses, as well as a lack of definitive diagnostic laboratory tests can complicate the diagnosis and result in delayed treatment, which can beget permanent vision loss. This review focuses on recent advances in areas of pathophysiology, classification, diagnosis and treatment. RECENT FINDINGS: Sympathetic ophthalmia is thought to involve a cell-mediated immune response to retinal and uveal antigens exposed through trauma or surgery. Multiple mechanisms have been implicated, including activation of the interleukin-23/IL-17 pathway. Ongoing emphasis is placed on early disease recognition and prompt treatment with multimodal imaging. Multiple authors advocate for the routine use of optical coherence tomography (OCT) for screening and disease monitoring. Systemic steroids and steroids sparing-immunosuppressive agents remain the mainstay of treatment. SUMMARY: Understanding pathophysiology may provide useful targets for drug development, as well as allow for identification of patients at risk. OCT is a useful tool in early diagnosis and management of sympathetic ophthalmia, as OCT changes may precede clinical symptoms and signs, allowing for early disease detection and better visual 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.

Sympathetic ophthalmia after 27-G pars plana vitrectomy.

BACKGROUND: Sympathetic ophthalmia (SO) is a bilateral diffuse uveitis that can arise after ocular trauma or ocular surgery in the inciting eye. Pars plana vitrectomy (PPV) is one of the risk factors for SO. Several reports have described SO developing after 23- and 25-G PPV, but none have described SO occurring after 27-G PPV. We describe herein a case of SO after 27-G PPV for rhegmatogenous retinal detachment. CASE PRESENTATION: A 42-year-old woman presented with visual disturbance in the right eye. Best-corrected visual acuity (BCVA) was 6/200 in the right eye. Fundus examination revealed off-macula retinal detachment with retinal tears at both ends of retinal lattice degeneration at the temporal-oven peripheral retina of the right eye. We therefore performed 27-G sutureless PPV on the right eye. After 12 days, the retina was reattached, and BCVA improved to 6/30 in the right eye. Fifteen days postoperatively, she experienced headache and reduced vision in both eyes. Symptoms gradually worsened, and she visited our hospital 21 days postoperatively. BCVA was 6/30 in the right eye and 6/15 in the left eye. Slit-lamp examination revealed uveitis in the anterior chambers of both eyes, and fundus examination showed papillitis and subretinal detachment at the posterior poles of both eyes. Optical coherence tomography revealed subretinal fluid in the maculae of both eyes and fluorescein angiography showed multiple hyperfluorescent leakage sites in the retinal pigment epithelium. Cerebrospinal fluid examination showed pleocytosis and human leukocyte antigen testing showed expression of the DR04 phenotype; therefore, the patient was diagnosed with SO. She was treated with steroid therapy, and her visual disturbance subsided and the subretinal fluid improved as well. Her BCVA was 6/15 for the right eye and 6/5 for the left eye 93 days after the initial surgery. CONCLUSION: The present case shows that even if the sclerotomy site of 27-G PPV is small, there is still a risk of SO occurring in the eyes of patients who underwent transconjunctival vitrectomy. Ophthalmologists should recognize SO as complication of 27-G PPV and carry out proper management as early as possible.