Incidence of Sympathetic Ophthalmia after Intraocular Surgery: A Systematic Review and Meta-analysis.

TOPIC: Sympathetic ophthalmia (SO) is a rare bilateral granulomatous panuveitis that can present after trauma or intraocular surgery (IOS). The incidence of SO after IOS varies among studies. The purpose of this review was to determine the incidence proportion of SO after IOS. CLINICAL RELEVANCE: The incidence proportion of SO after IOS can provide physicians and patients with information on the risk of SO during the consent process before surgery. METHODS: In this systematic review and meta-analysis, MEDLINE, EMBASE, and Cochrane databases were searched from inception to January 1, 2023 for population-based studies of SO after IOS. Two reviewers independently screened the results. Random-effects meta-analyses calculated incidence proportion. Subgroup analysis assessed SO incidence based on IOS type and technological advancements. Study quality and bias were assessed using the Newcastle-Ottawa scale and the Grades of Recommendation, Assessment, Development, and Evaluation framework. RESULTS: The final meta-analyses included 19 studies, with 118 cases of SO occurring after 505 178 inciting events. The estimated overall incidence proportion of SO after IOS was 0.061% (95% confidence interval [CI], 0.033%-0.111%; I2 = 83%), and the estimated incidence rate was 9.24 cases per 100 000 person-years (95% CI, 4.03-21.19; I2 = 88%). The average study duration across these studies was 10.8 years. Within the reviewed literature, SO after glaucoma and vitreoretinal IOS was studied most, with 9 and 6 studies, respectively. Observed differences in incidence between glaucoma (0.098%; 95% CI, 0.042%-0.232%; I2 = 40%) and vitreoretinal (0.043%; 95% CI, 0.022%-0.085%; I2 = 88%) IOS were not statistically significant (P = 0.14). Also, no significant difference was found in the incidence proportion before and after 1975, when modern intraocular surgical techniques emerged (0.060% vs. 0.058%; P = 0.98). The outcome measures showed low-certainty Grades of Recommendation, Assessment, Development, and Evaluation evidence. DISCUSSION: Sympathetic ophthalmia after IOS is rare and might not have changed over the past 5 decades. The estimated incidence proportion of SO may be useful during the consent process before surgery. Also, no significant difference may exist in the incidence of SO between glaucoma and vitreoretinal IOS, based on low-certainty evidence. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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.

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.

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.

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.

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.

Exudative Retinal Detachment in Ocular Inflammatory Diseases: Risk and Predictive Factors.

PURPOSE: This study evaluated the risk and risk factors for exudative retinal detachment (ERD) in ocular inflammatory diseases. DESIGN: Retrospective cohort study. METHODS: Patients with noninfectious ocular inflammation had been followed longitudinally between 1978 and 2007 at 4 US subspecialty uveitis centers. The main outcome measurements were occurrences of ERD and predictive factors. RESULTS: A total of 176 of 14,612 eyes with ocular inflammation presented with ERD. Among uveitis cases, Vogt-Koyanagi-Harada syndrome (VKH) (odds ratio [OR] = 109), undifferentiated choroiditis (OR = 9.18), sympathetic ophthalmia (OR = 8.43), primary or secondary panuveitis (OR = 7.09), multifocal choroiditis with panuveitis (OR = 4.51), and "other" forms of posterior uveitis (OR = 16.9) were associated with a higher prevalence of ERD. Among the 9,209 uveitic or scleritic eyes initially free of ERD and followed, 137 incident ERD cases were observed over 28,949 eye-years at risk (incidence rate = 0.47% [0.40%-0.56%/eye-year]). VKH (HR = 13.2), sympathetic ophthalmia (HR = 5.82), undifferentiated choroiditis (HR = 6.03), primary or secondary panuveitis (HR = 4.21), and rheumatoid arthritis (HR = 3.30) were significantly associated with incident ERD. A significant dose-response relationship with the prevalence and incidence of ERD were observed for AC cells and vitreous cell activity. African Americans had significantly higher prevalence and incidence of ERD. CONCLUSIONS: Other ocular inflammatory conditions in addition to VKH syndrome and posterior scleritis were associated with increased risk of ERD, indicating that ERD does not necessarily dictate a diagnosis of VKH or posterior scleritis. In addition, the relationship between ERD and inflammatory severity factors implies that inflammation is a key predictive factor associated with developing ERD and requires early and vigorous control.

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.].