Purpose
To describe the frequency, risk factors, management, and outcome of eyes with tubercular serpiginous-like choroiditis showing continued progression following initiation of antituberculosis treatment.
Design
Retrospective, comparative, interventional case series.
Methods
setting : Institutional. P atient population : One hundred ten patients of serpiginous-like choroiditis with 1) complete records, 2) tuberculin skin test, 3) active lesions in at least 1 eye, and 4) minimum 18 months follow-up. intervention : Based on the positivity of tuberculin skin test, the patients were categorized in Group A (84 patients with positive tuberculin test) and Group B (26 patients with negative tuberculin test). Of the 84 patients in Group A, 19 received systemic corticosteroids while 65 also received 4-drug antituberculosis treatment in addition. All patients in Group B received corticosteroids. Patients with continued progression received an increased dose of corticosteroids with or without immunosuppressive agents. main outcome measure : Development of continued progression.
Results
There were 61 men and 23 women in Group A and 19 men and 7 women in Group B. Continued progression was observed in 12 patients (14.28%) in Group A and none in Group B ( P = .04). Of the 12 patients in Group A showing progression, 11 (16.9%) were receiving antituberculosis treatment and corticosteroids. The lesions responded in all eyes, and final visual acuity of 20/40 or better could be achieved in 10 eyes (75%).
Conclusion
Continued progression of choroiditis lesions occurs in 14% of patients after initiating antituberculosis treatment in tubercular serpiginous-like choroiditis. Increased immunosuppression with continuation of antituberculosis treatment resulted in good outcome.
Serpiginous choroiditis has traditionally been described as bilateral, chronic, recurrent inflammation of the choriocapillaris, choroid, and retinal pigment epithelium (RPE). The disease is believed to be autoimmune in etiology and is managed with systemic corticosteroids and immunosuppressive agents. Tubercular serpiginous-like choroiditis is a relatively new disease entity where serpiginous-like choroiditis is seen in patients with evidence of systemic or latent tuberculosis. Tubercular serpiginous-like choroiditis has 2 distinct presentations in the eye: 1) multifocal choroiditis that is discrete and noncontiguous at first and progresses relentlessly to a diffuse, contiguous variety, acquiring an active advancing edge resembling serpiginous choroiditis; or 2) diffuse plaque-like choroiditis showing amoeboid spread. Tubercular serpiginous-like choroiditis is believed to represent an immune-mediated hypersensitivity reaction to the acid-fast bacilli ( Mycobacterium tuberculosis ) sequestrated in the RPE. Addition of antituberculosis treatment to the usual systemic corticosteroids and immunosuppressive agents helps in reducing the number of recurrences over a long-term follow-up. Quite a few patients in our anecdotal experience showed continued progression of the disease on initiating antituberculosis treatment that responded to therapy in 4 to 6 weeks. Recently, there was a single case published reporting Jarisch-Herxheimer reaction following initiation of antituberculosis treatment in a patient with retinal vasculitis and vitritis. It is important for the treating ophthalmologists to be aware of the occurrence of this phenomenon so as to avoid labeling the case as resistant infection or think of the possible nontubercular etiologies. However, there are no series describing the frequency, course, risk factors, management, long-term follow-up, and outcome of tubercular serpiginous-like choroiditis. The present study aims to describe the effect of antituberculosis treatment on the course of active tubercular serpiginous-like choroiditis, with long-term follow-up and outcome.
Material and Methods
The study is a retrospective analysis of 110 patients with a clinical diagnosis of serpiginous-like choroiditis seen between November 16, 1992 and January 19, 2009. Patients fulfilling the following inclusion criteria were enrolled: 1) complete clinical records of visual acuity, slit-lamp biomicroscopic examination, intraocular pressure, complications if any, and treatment records at the baseline and at all follow-up visits; 2) a documented positive (10 mm of induration or more) or negative tuberculin skin test at 48 to 72 hours; 3) evidence of active serpiginous choroiditis in at least 1 eye of the patient with or without any other evidence of inflammation in the anterior or posterior segment; and 4) minimum 18 months follow-up from the initiation of treatment.
Based on the positivity of tuberculin skin test, the patients were categorized in 2 groups: 84 patients in Group A had a positive tuberculin skin test and 26 patients in Group B had a negative tuberculin skin test.
Of the 84 patients in Group A, 65 received 4-drug antitubercular therapy (isoniazid, rifampicin, ethambutol, and pyrazinamide) in addition to the systemic corticosteroid therapy (1–1.5 mg/kg/day). The remaining 19 patients did not receive antituberculosis treatment and were treated with systemic corticosteroids alone (1–1.5 mg/kg/day). All 26 patients in Group B received systemic corticosteroids/immunosuppressive agents.
The main outcome measure was continued progression that was defined as progression of the choroiditis lesion(s) clinically or fluorescein angiographically or the development of new lesions in patients who were initiated on antituberculosis treatment. This included the lesions that continued to progress after initiation of therapy as well as lesions that initially seemed to respond but showed worsening or the development of new lesions after initiating antituberculosis treatment.
In eyes showing continued progression, logistic regression analysis was done to see if there was any correlation between the progression and patient-specific characteristics including the age, gender, or laterality of the disease; severity of tuberculin skin test; dose of corticosteroids; and eye-specific characteristics including baseline visual acuity, associated anterior segment inflammation, or vitritis. Patients who showed continued progression were treated with an increased dose of corticosteroids, including intravenous methylprednisolone in 2 patients; 4 patients in addition also received immunosuppressive agents. However, 3 patients continued to receive the same treatment without further increase in the corticosteroid dosage or addition of immunosuppressive agents. All patients continued to receive antituberculosis treatment. The patients were followed up further to see the response to increase in systemic corticosteroids/immunosuppressive agents. The increased dose was continued over the next few weeks until the lesions healed completely and then was slowly tapered over next 12 months. Immunosuppressive agents, wherever added, were administered for 12 to 18 months and were stopped before stopping antituberculosis treatment. The total duration for which the patients received antituberculosis treatment was 18 months. The patients were followed up for a minimum of 18 months (18–119 months) after the initiation of antituberculosis treatment to look for disease recurrences. “Recurrence” was defined as reactivation of lesions after a quiescence of 3 months.
Results
There were 61 men and 23 women in Group A and 19 men and 7 women in Group B. The mean age of presentation was 31.22 ± 9.66 years (range 12–54 years) in Group A and 35.07 ± 11.76 years (range 14–65 years) in Group B. The disease (active or inactive) was bilateral in 51 patients in Group A and 17 patients in Group B. Lesions were active bilaterally in 35 patients in Group A and 10 patients in Group B. The mean follow-up was 35 ± 28.27 months (range 12–165 months) and 40.6 ± 31.64 months (range 12–152 months) in Groups A and B respectively. The median follow-up was 24 months and 40 months, respectively, in Groups A and B.
Continued progression of lesion(s) was observed in 12 patients (14.28%; 13 eyes) in Group A as compared to none in Group B ( P = .04). The details of these patients are given in the Table 1 . All the patients were immunocompetent with no evidence of any systemic disease including HIV. Compliance to treatment was ensured in all.
| No. | Age (y) | Sex | Eye | Initial VA | Tuberculin Skin Test (mm) | Initial Treatment | Time to Progression (weeks) | Dose of CS at Time of Progression (mg) | Treatment Changed at Progression | Course After Progression | Revised Treatment | Follow-up (months) | Final VA |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 36 | M | RE | 6/12 | 15 × 15 | CS 60 mg | 8 | 50 | CS 50 mg + cyclophosphamide | Healed; then recurrences | ATT; no recurrence after ATT | 119 | CF (macular scar) |
| 2 | 17 | M | RE | 6/9 | 16 × 19 | CS 60 mg + ATT | 2 | 50 | i.v. methylprednisolone | Healed; then recurrences in both eyes | Revise ATT; no further recurrence | 75 | 6/6 |
| 3 | 24 | M | RE | 6/6 | 20 × 18 | CS 60 mg + ATT | 2 | 60 | No change | Another episode of progression at 10 weeks; healed | No change | 12 | 6/6 |
| 4 | 41 | M | BE | 6/6 | 13 × 13 | CS 40 mg + ATT | 2 weeks (both eyes) | 40 | CS 60 mg | Healed | No change | 40 | 6/6 (both eyes) |
| 5 | 22 | M | RE | 6/6 | 15 × 20 | CS 80 mg + ATT | 2 | 80 | CS 80 mg + azathioprine | Healed | No change | 21 | 6/6 |
| 6 | 17 | M | LE | 6/12 | 25 × 25 | CS 50 mg + ATT | 3 | 50 | i.v. methylprednisolone | Healed | No change | 52 | 6/6 |
| 7 | 30 | M | RE | 6/12 | 20 × 22 | CS 40 mg + ATT | 4 | 40 | No change | Healed | No change | 63 | 6/6 |
| 8 | 41 | M | RE | 6/6 | 15 × 17 | CS 50 mg + ATT | 26 | 50 | No change | Further progression at 39 days; healed CNVM | No change; intravitreal bevacizumab | 53 | 6/18 (macular scar after CNVM) |
| 9 | 27 | F | RE | 6/9 | 29 × 29 | CS 60 mg + ATT | 5 | 60 | CS 60 mg + azathioprine | Healed | No change | 53 | 6/12 |
| 10 | 30 | F | RE | 6/6 | 15 × 15 | CS 20 mg (started elsewhere + ATT) | 8 | 20 | CS 60 mg | Healed | No change | 41 | 6/9 |
| 11 | 20 | M | RE | 6/60 | 15 × 15 | CS 60 mg + ATT | 10 | 20 | CS 60 mg + azathioprine | Healed | No change | 18 | 6/60 |
| 12 | 29 | M | RE | 6/9 | 24 × 25 | CS 50 mg + ATT | 14 | 10 | CS 40 mg | Healed | No change | 24 | 6/6 |
Of the 12 patients in Group A showing continued progression, 11 (12 eyes) showed progression while receiving antitubercular therapy along with corticosteroids, whereas only 1 patient showed progression while receiving systemic corticosteroids alone. This patient showed an initial response to intravenous cyclophosphamide but had multiple recurrences for which he received antituberculosis treatment. The median time of the progression was 4 weeks from the time of initiating therapy, varying between 11 days and 6 weeks. At the time of developing continued progression, the dose of oral prednisolone ranged between 10 and 80 mg per day, with a median dose of 50 mg per day. The continued progression was managed with increasing the dosage of oral prednisolone in 9 patients (2 of them received intravenous methylprednisolone) with addition of immunosuppressive agents in 4 patients. The lesions started responding to revised therapy in all the patients and showed healing over the next 4 to 6 weeks, with none of them showing further progression. The remaining 3 patients were already receiving oral corticosteroids at a dose of 1 mg/kg/day at the time of recurrence and the dosage of oral corticosteroid was not increased further. Two of these patients showed continued progression over the next 8 weeks before healing and 1 started responding to the current therapy within the next 2 weeks.
During follow-up, of the 11 patients who were receiving antituberculosis treatment and corticosteroids, 1 patient showed recurrences. This patient had poor compliance of antituberculosis treatment due to abnormal liver function tests. Antituberculosis treatment was revised for this patient, to which he responded without further recurrences. A final visual acuity of 6/12 or better was achieved in 10 eyes (75%; Figures 1–5 ).
