Table 7.

The use of intravenous immunoglobulins in ophthalmic disease

Disease	Ref.	Study design	Intervention including dose and IVIg preparation used	Number of patients	Results/response
Ophthalmic IgA bullous disease	[247]	Case report	Monthly IVIg treatment, 4 g/kg per month, with graduate discontinuation following clinical improvement	1 patient with chronic cicatrizing conjunctivitis due to linear IgA bullous disease with poor response to topical or systemic CS	Improvement of clinical symptoms with maximal effect 10–12 days following infusion; decrease of circulating IgA anti-97-kDa epidermal protein
Mucous membrane pemphigoid (MMP)	[27]	Nonrandomized controlled trial	IVIg, 2 g/kg per cycle, cycles were repeated every 2–4 weeks, compared to conventional immunosuppressive therapy	16 patients that were equally divided to control and IVIg group	Remission was achieved after 4 months in IVIg group vs 8.5 months in control group; IVIg had less recurrence and decreased progression; p value < 0.05
Ocular Behcet's disease	[90]	Case series	IVIg 0.4 g/kg per day: 5 times in first week, 3 more in the next months and once every 20 days for total of 3 months	4 patients refractory to CS and cyclosporine A	Control of acute inflammation and preservation of remission for 1 year; marked improvement of visual acuity
Optic neuritis	[248]	RCT	27 patients were treated with IVIg (Gamimune N; Bayer Pharmaceutical Division, West Haven, CT, USA) 0.4 g/kg per day for 5 days followed by 3 monthly single cycles vs placebo (n = 28)	55 patients with multiple sclerosis and visual loss due to optic neuritis	No difference between treatment groups was observed; there was no absolute reversal of persistent visual loss; the trial was terminated by the National Eye Institute
	[249]	RCT	IVIg 0.4 g/kg per day (Immunoglobulin SSI liquid; Statens Serum Institute, Copenhagen, Denmark), infused on days 0–2, and 1 to 2 months later (n = 34) vs placebo (n = 34)	68 patients with recent visual accuracy loss; 34 patients received IVIg (of which 15 had multiple sclerosis), compared with 34 patients who received placebo (of which 8 patients had multiple sclerosis)	No immediate or delayed effects were observed; there was no change in visual acuity; MRI findings and visual evoked potential results
Inflammatory pseudotumor of orbit	[250]	Case report	IVIg 2 g/kg divided over 4 days	1 patient with inflammatory pseudotumor of the orbit, resistant to systemic CS, and radiation therapy	Both clinical and radiographic improvement within days
Birdshot retinochoroiditis	[251]	Case series	IVIg 0.4 g/kg per day for 4 days; then 0.6 g/kg per day for 2 days, every 4 weeks	37, of which 18 were followed up	Visual acuity of 53% of patients' eyes has increased by 2.6 ± 1.5; in 29% of patients, visual acuity remained stable, and in 18% of eyes VA have decrease
	[29]	Case series	IVIg 1.6 g/kg every month for 6 months, followed by 1.2–1.6 g/kg every 6–8 weeks	18 patients	In patients with visual acuity of 20/30, there was increase in visual acuity in 53.8% of eyes and decrease of acuity in 7.7% while there was no change in the remaining eyes
Orbital myositis	[252]	Case report	IVIg (Venimmun) 0.3 g/kg per day for 3 days	1 patient intolerant to CS treatment and poor clinical response	Both clinical and tomographic resolution within 2 weeks
Refractory uveitis	[253]	Case series	IVIg (Baxter Healthcare, Glendale, CA, USA), 0.5 g/kg per day for 3 days each month; median of 7.5 cycles	10 patients with poor response to immunosuppression (some cases were idiopathic, others were secondary to sarcoidosis, Behcet, inflammatory bowel disease, and birdshot retinochoroiditis)	50% sustained improvement of visual acuity, 20% have required a reduced doses of immunosuppressive therapy without disease progression; the patient with sarcoidosis had improved vision and reduced need for immunosuppression, although that effect was not sustained 4.5 months following treatment discontinuation; the Behcet patient showed marked improvement
	[254]	Case series	IVIg, 1–2.5 g/kg per cycle over 3 days; cycles were repeated every 2–4 weeks initially and every 5 to 6 weeks after effect was observed; treatment time averaged at 16.8 months	5 patients unresponsive to conventional therapy, of which 1 patient had juvenile idiopathic arthritis and 1 patient had psoriatic arthritis; 1 patient had retinal vasculitis and APLA; the other 2 cases were idiopathic	In 60% (2 idiopathic cases, 1 patient with vasculitis and APLA), treatment was effective in controlling inflammation, and visual acuity remained stable or improved
Graves' ophthalmopathy	[255]	Prospective nonrandomized	35 patients were treated with IVIg and 27 with CS	62 patients with Graves' ophthalmopathy	76% response in IVIg-treated patients compared to 66% in CS group, in a manner that was statistically insignificant; side effects were more common in patients receiving CS therapy
	[256]	RCT	21 patients were treated with 6 cycles of 1 g/kg IVIg for 2 days every 3 weeks; 19 patients were treated with oral prednisolone (starting dose 100 mg/day)	40 patients	No marked difference between IVIg (62% response) and prednisolone (63% response); both groups had significantly improved proptosis, visual acuity, decrease of intraocular pressure, and decrease of eye muscle area
Paraneoplastic visual loss	[257]	Case series	2 patients were treated with IVIg 0.4 mg/kg per day for 5 days; 1 patient received single-dose d/t treatment intolerance	3 patients	1st patient improved from distinguishing hand movement to 20/40 and 20/50 OS; improved visual fields
					2nd patient, no improvement
					3rd patient, improved visual field without change in visual acuity
	[258]	Case report	IVIg, as well as radiotherapy and surgical resection	1 patient with melanoma-associated retinopathy	Improvement in visual fields over 1 year of follow-up