Sympathetic ophthalmia is a bilateral diffuse granulomatous panuveitis that occurs after accidental or surgical insult involving the uveal tract of one eye. After an initial injury from either planned or accidental insult to the eye, a sight-threatening inflammation can develop in both eyes after a variable period. The incidence of sympathetic ophthalmia was estimated to be between 0.2% and 0.5% after penetrating ocular injuries and 0.01% after intraocular surgery.1,2 Sympathetic ophthalmia usually rapidly responds to corticosteroid therapy, but recalcitrant cases and cases with recurrences may require additional corticosteroid-sparing immunosuppressive agents.
The incidence of sympathetic ophthalmia in the pediatric age group was estimated to be 0.24% in a study from India.3 The ocular morbidity assumes paramount significance in sympathetic ophthalmia because of its potential to cause blindness in both eyes following an insult or injury to one eye. Thus, recognition of the signs and symptoms of sympathetic ophthalmia is crucial because the disease is vision threatening, and many patients may end up with significant vision loss, especially if rapid and effective treatment is not initiated. The management of sympathetic ophthalmia in the pediatric age group is challenging because of the difficulty of comprehensive ophthalmic evaluations and potential side effects of various systemic immunomodulators, especially corticosteroids, to treat the condition. The current study was undertaken to examine the clinical profile of patients aged 18 years and younger with sympathetic ophthalmia who attended a tertiary eye care center in southern India in the past 20 years. To the best of our knowledge, the current study is the largest case series on pediatric sympathetic ophthalmia.
Patients and Methods
This was a hospital-based retrospective case series that reviewed the files of all consecutive patients aged 18 years and younger with sympathetic ophthalmia at a single tertiary center between December 1997 and January 2017. Patients with insufficient documentation or a history of traumatic anterior uveitis were excluded from the study. A diagnosis of sympathetic ophthalmia was made in patients with bilateral panuveitis following a history of trauma or surgery preceding the onset of intraocular inflammation in the other eye. A clinical diagnosis of sympathetic ophthalmia was considered for patients with bilateral granulomatous panuveitis that occurred after a definite history of ocular trauma or surgery, exclusion of other pathologies (eg, Vogt-Koyanagi-Harada disease), infectious etiologies, and autoimmune causes (eg, sarcoidosis). All patients underwent a detailed medical evaluation that included medical history, best corrected visual acuity (BCVA) and visual field assessment, slit-lamp biomicroscopy, intraocular pressure (IOP) measurement by applanation tonometry, and indirect ophthalmoscopy. All of the patients underwent fundus fluorescein angiography and B-scan ultrasonography.
The data including sex, age, clinical presentation, ocular involvement, type of ocular injury, time of injury, and time from the first injury to the development of disease and presentation were entered into a computer database. Visual outcomes and subsequent incidence of ocular complications such as cataract, ocular hypertension, hypotony, macular edema, choroidal neovascularization, subretinal fibrosis, and retinal detachment were also recorded. Uveitis was classified according to the Standardization of Uveitis Nomenclature Working Group classification. BCVA results were converted to logarithm of the minimum angle of resolution (logMAR) for statistical analysis and are presented as logMAR and Snellen equivalent. Improvement in visual acuity was defined as a two-step increase in BCVA on Snellen chart. Improvement in visual acuity was graded as good, fair, or poor depending on whether the final BCVA was 6/12 or better, 6/12 to 6/60, or 6/60 or worse, respectively. Ocular hypertension was defined as an IOP higher than 21 mm Hg, and ocular hypotony was defined as an IOP lower than 6 mm Hg.
All statistical analyses were performed using SPSS statistical package software (version 14.0; SPSS, Inc., Chicago, IL). Statistical tests with a P value of less than .05 were considered statistically significant. Descriptive statistics were used for continuous variables, and frequency distribution was used to determine the distribution of qualitative variables. The Wilcoxon signed-rank test was used to determine the difference in visual acuity between presentation and the final follow-up.
The current study included 20 patients aged 18 years and younger who were diagnosed as having sympathetic ophthalmia. Fourteen patients (70%) were male and 6 (30%) were female. The mean age at presentation was 11 ± 3.1 years (range: 5 to 17 years), and the majority of the patients (60%) were between 6 and 12 years of age. The inciting event of sympathetic ophthalmia was penetrating trauma in 17 patients (85%), whereas 3 patients (15%) developed sympathetic ophthalmia following vitreoretinal procedures. Among the 17 patients with penetrating trauma, 4 (20%) had a history of some form of surgical intervention for the management of penetrating injury. The diagnosis of sympathetic ophthalmia in the current study was clinical in the majority of the patients. Histopathological confirmation of sympathetic ophthalmia was obtained in 2 patients following enucleation, which suggested chronic granulomatous inflammation involving the retina and choroid. The patients' demographics and clinical profile are listed in Table 1.
Characteristics of the Study Population With Sympathetic Ophthalmia
Varying degrees of anterior chamber inflammation was observed in 14 sympathizing eyes (70%). Inflammation in vitreous was noted in 16 sympathizing eyes (80%). Subretinal fluid at the posterior pole was observed in 9 eyes (45%), and swelling of the optic disc was noted in 5 eyes (25%). The median time from initial injury to onset of symptoms of sympathetic ophthalmia was 54 days (range: 10 to 5,416 days). In the current study, 13 patients (65%) developed sympathetic ophthalmia within 2 months from the initial injury. In 7 patients (35%), the onset of symptoms was delayed by more than 6 months. One of our patients, who underwent multiple vitreoretinal surgeries for the management of retinopathy of prematurity during infancy, developed sympathetic ophthalmia in another eye approximately 15 years (5,416 days) later.
All of the patients in the current study received systemic corticosteroids. Nine patients (45%) received pulse corticosteroid (intravenous methylprednisolone 1 gram for 3 days) and subsequently started an oral corticosteroid in a tapering schedule. Seventeen patients (85%) received a corticosteroid-sparing immunosuppressive agent. In the current study, azathioprine was the most commonly used first-line corticosteroid-sparing immunosuppressive agent (70%), followed by methotrexate (15%). Of the 17 patients who received corticosteroid-sparing immunosuppressive agents, 4 patients (20%) required more than one immunosuppressive agent (cyclosporine) to achieve complete remission. The average duration of corticosteroid-sparing immunosuppression therapy to control inflammation was 7.85 months (range: 2.5 to 22 months). Two children developed Cushingoid features and were switched to corticosteroid-sparing immunosuppressive agents. None of the patients receiving corticosteroid-sparing immunosuppressive therapy developed any side effects. The most common complication observed in the current study was cataract (10 patients, 50%), followed by ocular hypertension (6 patients, 30%) and subretinal fibrosis (3 patients, 15%). Four patients required surgical interventions for the management of these complications: 3 patients underwent cataract surgery and 1 patient required a filtration procedure for the control of IOP.
The mean duration of follow-up in the current study was 462 ± 64.8 days (range: 339 to 2,660 days). Mean BCVA of the sympathizing eye at presentation was 1.15 ± 0.99 logMAR, which improved to 0.54 ± 1.00 logMAR by the final follow-up. The improvement in BCVA was statistically significant (P =.022). The mean BCVA in the exciting eye was 2.21 ± 1.04 logMAR at presentation and 2.21 ± 1.14 logMAR at the time of the final follow-up. Interestingly, 3 of the exciting eyes in the current study had good visual outcomes after the treatment. Visual outcome was good in 14 eyes (70%), fair in 3 eyes (15%), and poor in 3 sympathizing eyes (15%). Of the 3 eyes with poor visual outcome, 1 had glaucomatous optic nerve damage and 2 developed extensive subretinal fibrosis.
Sympathetic ophthalmia is a dreaded cause of childhood blindness. Louis Braille, who became completely blind at the age of 5 years, was a victim of this dreaded entity.4 Ocular trauma remains a leading cause of visual impairment in children. Sympathetic ophthalmia is not uncommon in children, but there is a considerable paucity of literature on pediatric sympathetic ophthalmia.3 In the current study, we evaluated our experience with sympathetic ophthalmia in patients aged 18 years and younger over a 20-year period. The results of this study must be interpreted with caution because of its retrospective nature and relatively small sample size. Despite the small sample size, the current study is the largest study on pediatric sympathetic ophthalmia to the best of our knowledge.3
Recent studies reported a relative increase in cases of sympathetic ophthalmia following surgical intervention compared with sympathetic ophthalmia due to penetrating trauma.5–7 With the advent of new and improved methods of vitreoretinal surgery, the number of instances when vitreoretinal procedures were undertaken to preserve the functional and structural integrity of the eyeball following penetrating injury increased significantly in past few decades. Additionally, it is often difficult to attribute the primary mechanism of uveal tract incarceration in patients who sustained a penetrating injury and subsequently underwent surgical interventions. Surgical intervention was considered to be the inciting event for sympathetic ophthalmia development in three patients in the current study because none of the patients had any antecedent history of previous ocular injury. In contrast, it would be difficult to identify the primary inciting event in the 4 patients in the current study who had a history of surgical intervention following antecedent trauma.
The current results show comparable data regarding mean age at presentation, male predominance, and clinical presentations, with respect to a previous study.3 Although sympathetic ophthalmia usually develops within 3 months after injury in most patients, late onset of the disease among the pediatric age group is not uncommon. In the current study, sympathetic ophthalmia manifested in 35% of patients 6 months after the inciting events. Also, one of our patients developed sympathetic ophthalmia approximately 15 years after the multiple vitreoretinal procedures for retinopathy of prematurity. Sympathetic ophthalmia has been reported 66 years after penetrating injury.8 Our data showed the importance of adequately counseling the parents of children with penetrating injuries or multiple intraocular surgeries about the possibility of developing sympathetic ophthalmia in the uninvolved eye in the future.
In contrast to a similar study from India3 that reported using corticosteroid-sparing immunosuppressive agents in 50% of patients, 85% patients in the current study received corticosteroid-sparing immunosuppressive agents. Corticosteroid-sparing immunosuppressive agents play an important role in the management of sympathetic ophthalmia. They help to achieve long-term control of the inflammation and to attain a corticosteroid-sparing effect. This is crucial in children because the potential side-effects of long-term corticosteroid therapy are manifold. In the current study, azathioprine was the most commonly used corticosteroid-sparing immunosuppressive agent (70%). In accordance with previous literature, we found this agent to be relatively safe and well tolerated in children because none of the patients in the current study developed any side effects.
When compared with other similar studies, our study had relatively better visual outcomes.3,6 A good visual outcome (6/12 or better) in the sympathizing eye was achieved in 70% of the patients in the current study, whereas the proportion of patients achieving a similar visual outcome in the sympathizing eye was much lower in the study by Kumar et al.3 Similarly, Su and Chee6 reported 43% of their patients achieved a final visual acuity of 6/15 or better. This observation can be attributed to the relatively higher use of corticosteroid-sparing immunosuppressive agents in the current study.
Sympathetic ophthalmia is a rare and potentially visually devastating condition in children, typically occurring after multiple vitreoretinal surgeries or non-surgical penetrating injury to one eye. A high index of suspicion is vital to ensure early diagnosis and treatment. Creating awareness among the parents of the possibility of developing sympathetic ophthalmia in the uninvolved eye is of utmost importance for early recognition and management. Prompt and effective management with corticosteroid-sparing immunosuppressive therapy may allow control of the disease and retention of good visual acuity in both the sympathizing and exciting eyes.
- Makley TA, Azar A. Sympathetic ophthalmia. A long-term follow-up. Arch Ophthalmol. 1978;96(2):257–262. doi:10.1001/archopht.1978.03910050125004 [CrossRef]
- Marak GE Jr, . Recent advances in sympathetic ophthalmia. Surv Ophthalmol. 1979;24(3):141–156. doi:10.1016/0039-6257(79)90018-3 [CrossRef]
- Kumar K, Mathai A, Murthy SI, et al. Sympathetic ophthalmia in pediatric age group: clinical features and challenges in management in a tertiary center in southern India. Ocul Immunol Inflamm. 2014;22(5):367–372. doi:10.3109/09273948.2013.841958 [CrossRef]
- Jiménez J, Olea J, Torres J, Alonso I, Harder D, Fischer K. Biography of Louis Braille and invention of the Braille alphabet. Surv Ophthalmol. 2009;54(1):142–149. doi:10.1016/j.survophthal.2008.10.006 [CrossRef]
- Kilmartin DJ, Dick AD, Forrester JV. Prospective surveillance of sympathetic ophthalmia in the UK and Republic of Ireland. Br J Ophthalmol. 2000;84(3):259–263. doi:10.1136/bjo.84.3.259 [CrossRef]
- Su DH-W, Chee S-P. Sympathetic ophthalmia in Singapore: new trends in an old disease. Graefes Arch Clin Exp Ophthalmol. 2006;244(2):243–247. doi:10.1007/s00417-005-0009-4 [CrossRef]
- Rishi E, Rishi P, Appukuttan B, Walinjkar J, Biswas J, Sharma T. Sympathetic ophthalmitis following vitreoretinal surgery: does antecedent trauma make a difference?Indian J Ophthalmol. 2015;63(9):692–698. doi:10.4103/0301-4738.170980 [CrossRef]
- Zaharia MA, Lamarche J, Laurin M. Sympathetic uveitis 66 years after injury. Can J Ophthalmol. 1984;19(5):240–243.
Characteristics of the Study Population With Sympathetic Ophthalmia
| Male||14 (70%)|
| Female||6 (30%)|
|Mean ± age of presentation (range)||11 ± 3.1 years (5 to 17 years)|
| 0 to 5 years||2 (10%)|
| 6 to 12 years||12 (60%)|
| 13 to 18 years||6 (30%)|
| Trauma||13 (65%)|
| Surgical intervention||3 (15%)|
| Trauma followed by surgical intervention||4 (20%)|
| Anterior chamber reaction||14 (70%)|
| Vitritis||16 (80%)|
| Subretinal fluid/exudative retinal detachment||9 (45%)|
| Optic disc swelling||5 (25%)|
|Median time interval between inciting event and onset of sympathetic ophthalmia (range) Treatment||54 days (10 to 5,416 days)|
| Systemic corticosteroid|
| Oral corticosteroid||20 (100%)|
| Pulse corticosteroid||9 (45%)|
| Immunosuppressive agent||17 (85%)|
| Azathioprine||14 (70 %)|
| Methotrexate||3 (15%)|
| Cyclosporine||4 (20%)|
| Average duration of immunosuppression therapy (range)||7.85 months (2.5 to 22 months)|
| Cataract||10 (50%)|
| Ocular hypertension||6 (30%)|
| Subretinal fibrosis||3 (15%)|
| Extensive depigmentation||3 (15%)|
|BCVA in sympathizing eye|
| At presentation||1.15 ± 0.99 logMAR|
| At final follow-up||0.54 ± 1.00 logMAR|
| Improvement in BCVA|
| Good (6/12 or better)||14 (70%)|
| Fair (6/12 to 6/60)||3 (15%)|
| Poor (6/60 or worse)||3 (15%)|
|BCVA in exciting eye|
| At presentation||2.21 ± 1.04 logMAR|
| At final follow-up||2.21 ± 1.14 logMAR|
| Improvement in BCVA|
| Good (6/12 or better)||3 (15%)|
| Fair (6/12 to 6/60)||2 (10%)|
| Poor (6/60 or worse)||15 (75%)|