What is the role of Intravenous Immunoglobulin (IV-Ig) in treating ophthalmological conditions?

IV Immunoglobulin in Ophthalmology

IV immunoglobulin (IVIg) has no proven benefit for ocular complications in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), but is effective as steroid-sparing therapy in ocular cicatricial pemphigoid (OCP) and recurrent-relapsing inflammatory optic neuropathy.

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN)

Evidence Against Use

• The British Association of Dermatologists guidelines explicitly state there is no robust evidence for IVIg to improve ocular outcomes when given in the acute phase of SJS/TEN 1
• A retrospective case series comparing 8 TEN patients treated with IVIg (2 g/kg over 2 days) to 8 historical controls found no difference in severity of visually significant ocular complications at 6 weeks post-treatment 1
• A multicenter study of 43 patients treated with various systemic therapies (including IVIg alone, steroids alone, or combination) could not demonstrate therapeutic benefit from systemic immunomodulatory treatment to mitigate ocular complications 1, 2

Pediatric Population Exception

• Some data suggest potential benefit in children, with case series showing good outcomes in 33 children with TEN and 6 with SJS-TEN overlap treated with IVIg (0.25-1.5 g/kg daily for 1-5 days), though this may simply reflect better prognosis in pediatric patients 1
• However, one pediatric series reported higher rates of ophthalmic complications in children given IVIg compared to those who were not, and IVIg carries risk of renal impairment 1

Ocular Cicatricial Pemphigoid (OCP)

Strong Evidence for Efficacy

• IVIg monotherapy (2 g/kg/cycle over 3 consecutive days monthly) achieved remission in 76.5% (26/34 eyes) of patients with recalcitrant OCP in a long-term follow-up study 3
• IVIg showed 100% efficacy in stage 1 OCP (7/7 eyes) 3
• In a prospective study of 10 OCP patients who failed conventional therapy, 8 patients who completed the IVIg protocol (20-42 cycles over 25-43 months) had improved visual acuity, no further progression of subepithelial conjunctival fibrosis, and sustained remission for 24-48 months after discontinuation 4

Dosing Protocol

• Standard dosing: 2 g/kg per cycle administered over 3 consecutive days, given monthly 4, 3
• Total cycles ranged from 20-42 (mean 32) in successful cases 4
• Gradual withdrawal is critical—abrupt cessation can result in severe recurrence progressing to blindness 4

Critical Pitfall

• Ocular surgery is associated with OCP relapse: 2 of 9 eyes (22.2%) that underwent cataract surgery after achieving remission experienced relapse 3
• Two patients who had IVIg abruptly discontinued (one involuntarily withdrawn, one not provided postoperatively after ocular surgery) experienced worsening disease and vision loss 4

Recurrent-Relapsing Inflammatory Optic Neuropathy

Steroid-Sparing Role

• IVIg stabilized vision in all 6 patients with steroid-responsive recurrent-relapsing optic neuropathy without requiring steroids for extended periods 5
• 5 of 6 patients no longer required corticosteroids after IVIg treatment, with average prior steroid use of 12 months 5
• Vision stabilized (none improved, none worsened) during IVIg maintenance 5

Limitations

• Two patients experienced late relapses on IVIg, requiring addition of cyclosporine or steroids 5
• IVIg appears to maintain stability rather than improve vision 5

Safety Profile

Common Adverse Effects

• Mild and transient reactions occur in 24-36% of infusions: headaches, flushing, fever, chills, fatigue, nausea, diarrhea, blood pressure changes, and tachycardia 6
• One adverse event occurred after 3 uneventful years of IVIg maintenance in the optic neuropathy series 5

Serious Complications (Rare)

• Acute renal failure occurs primarily in insufficiently hydrated patients and with sucrose-stabilized products due to osmotic injury 6
• Thromboembolic events due to hyperviscosity, especially in patients with advanced age, previous thromboembolism, immobilization, diabetes, hypertension, or dyslipidemia 6
• Anaphylaxis in IgA-deficient patients 1
• Aseptic meningitis 1

Prevention Strategies

• Slow infusion rate and adequate hydration prevent renal failure, thromboembolic events, and aseptic meningitis 6
• Avoid in patients with known risk factors for thromboembolism 6

Pemphigus Vulgaris Context

• A double-blind, placebo-controlled study in 61 pemphigus vulgaris patients confirmed IVIg efficacy (1-2 g/kg over 5 days), with dose-response effect and significant clinical improvement by day 8 in the higher-dose arm 1
• IVIg is typically used at 2 g/kg in divided doses over several days, given at monthly intervals, often requiring prolonged treatment for continued effect 1
• IVIg acts by increasing pathogenic catabolism of antibodies and does not increase infection risk compared to other adjuvant therapies 1