Table 1.
Summary of Recent Global Case Studies and Case Series of IOI, Retinal Vasculitis, and Retinal Vascular Occlusive Events after Intravitreal Brolucizumab Treatment in Patients With nAMD
| Study | N | Presenting Symptoms | Examination Findings | Treatment | Resolution |
| Angerer, 202035 | 1 eye | Swollen eyelids and foreign body sensation initially; eye pain and vision loss | Vision was 1/30 on hand chart (from 0.05), internal pressure of 33 mm Hg, moderate Descemet folds, AC cells, fundus view was reduced, and choroidal detachment | Ofloxacin eye drops TID initially; intravenous aciclovir 500 mg TID, prednisolone acetate eye drops 5 times daily; switch to 900-mg oral valganciclovir BID (because of initial suspicion of herpes zoster–associated uveitis); subsequently, parabulbar administration of fortecortin and systemic prednisolone 100 mg daily | Pale optic disc, “ghosting” of the central arteries, obliterations of retinal vessels in the periphery, intraretinal bleeding. Vision no longer increased |
| Iyer 202019 | 1 eye | Pain, ocular aches, floaters, and decreased vision | VA decreased from 20/70–20/200, AC cells (0.5+), vitreous debris, arterial plaques, vascular sheathing, boxcarring, and retinal whitening; subsequently, VA decreased to count fingers at 3 feet, fine keratic precipitates, AC cells (2+), posterior debris and haze, and worse retinal whitening | Topical 1% prednisolone acetate; subsequently, 0.05% difluprednate drops every 2 hours and oral high-dose methylprednisolone pulse therapy, pars plana vitrectomy with intravitreal triamcinolone injection | Vision improved to 20/200 |
| Antaki 202120 | 1 eye | Pain, vision loss | VA reduced to light perception (from 20/150), moderate to severe vitritis, arterial sheathing, diffuse arterial and venous narrowing, perivenular hemorrhages, filling defects, and peripheral nonperfusion | — | — |
| Enriquez 202136 | 14 eyes of 13 patients | Symptoms of 1 patient described: floaters and blurred vision | IOI with anterior segment and/or vitreous cells | Topical and/or oral corticosteroids, sub-Tenon triamcinolone acetonide, vitrectomy, and/or intraoperative triamcinolone; or no treatment | 11 eyes switched to a different anti-VEGF |
| Hikichi, 202121 | 3 eyes of 3 patients | Ocular redness, pain, and decreased vision | BCVA decreased to 0.3 (from 1.2), ciliary hyperemia, AC (1+) cells, fine keratic precipitates without fibrin material, anterior vitreous cells (2+), slight vitreous haze; subsequently, hypopyon and vitreous opacities, BCVA decreased to HM | Topical 0.01% betamethasone sodium phosphate QID; subsequently, sub-Tenon 20 mg triamcinolone acetonide | Anterior chamber inflammation resolved; subsequently, hypopyon resolved, vitreous opacities decreased with improved BCVA to 0.5 |
| Ocular pain, redness, and blurred vision | BCVA decreased to 0.06 (from 0.3), conjunctival hyperemia, AC cells (1+), fine keratic precipitates, vitreous cells, vitreous opacities, intraretinal hemorrhage, vitreous haze, and sheathed inferior and inferotemporal retinal veins | Topical 0.01% betamethasone sodium phosphate QID and sub-Tenon 20-mg triamcinolone acetonide | Anterior chamber inflammation resolved, vitreous opacities decreased, BCVA recovered to 0.3, resolution of retinal hemorrhage, and reduction of the sheathed retinal vessels | ||
| Floaters and gradual progression to blurry vision without redness or pain | BCVA decreased to 0.6 (from 0.7), no ciliary hyperemia, rare AC cells, fine keratic precipitates, some vitreous opacities, sheathed retinal arteries and veins, and IRF and SRF recurrence | Topical 0.01% betamethasone sodium phosphate QID and sub-Tenon 20-mg triamcinolone acetonide injection | Vitreous opacities resolved, BCVA recovered to 0.7, and sheathed retinal vessels seemed to improve | ||
| Kataoka, 202122 | 3 eyes of 3 patients | Blurry vision described as “white out” | VA reduced to 0.1 (from 0.6), AC cells (1+), fine keratic precipitates, vitreous cells (1+), no hypopyon, aqueous flare, vitreous haze, sheathing of peripheral retinal arteries and veins, blot retinal hemorrhage, leakage from veins at arcades and the peripheral retina, leakage from optic nerve head, and appearance of subretinal hyperreflective material | Oral prednisolone 30 mg per day and sub-Tenon triamcinolone acetonide injection (20 mg/0.5 mL) and 0.1% betamethasone eye drops QID | Vascular sheathing disappeared, no evidence of inflammation on FA, subretinal hyperreflective material decreased, VA recovered to 0.8, and aqueous flare decreased to levels comparable with fellow eye |
| Floaters | AC cells (1+), fine keratic precipitates, vitreous cells (1+), aqueous flare, vitreous haze, sheathing on peripheral retinal arteries and veins, blot retinal hemorrhage, filling defects, areas of nonperfusion in the peripheral retina, and segmental leakage in peripheral veins; subsequently, VA worsened from 0.5 to 0.3 | Oral prednisolone 30 mg per day, sub-Tenon triamcinolone acetonide injection (20 mg/0.5 mL), and 0.1% betamethasone eye drops QID | Vascular sheathing disappeared, VA recovered to 0.5, aqueous flare decreased to levels comparable with fellow eye, and no evidence of inflammation on FA | ||
| Blurry vision, floaters, and redness | VA reduced to 0.6 (from 1.5), slight conjunctival injection, AC cell (1+), fine keratic precipitates, vitreous cell (2+), thick vitreous opacities, blot hemorrhage in the peripheral retina, filling defects in the peripheral retinal arteries and veins, an area of nonperfusion in the peripheral retina, and diffuse leakage from retinal vessels and optic nerve head; subsequently VA worsened to 0.3 | Oral prednisolone 30 mg per day, sub-Tenon triamcinolone acetonide injection (20 mg/0.5 mL), and 0.1% betamethasone eye drops QID | Decreased leakage, VA recovered to 1.5, improvement in vitreous haze, and disappearance of retinal hemorrhage | ||
| Kaupke, 202137 | 1 eye | VA loss that had persisted for 2 days, redness, and feeling of pressure | AC cells and conjunctival injection; subsequently, VA reduced to HM from 0.1, retinal hemorrhages, and increased AC irritation | Dexamethasone and gentamicin eye drops QID; subsequently, prednisolone 40 mg increased to 100 mg for 3 days | 5 months after first presentation, the eye was completely blind and showed retinal atrophy |
| Kessler, 202130 | 2 eyes of 1 patient | “Thundercloud” appearance OS after first brolucizumab injection; vision loss OU after second brolucizumab injection | BCVA was 0.1 OD and 0.05 OS, granulomatous precipitates, pronounced AC flare, and numerous vitreous cells. Vision OS was blurred, and ischemia of the upper hemisphere of the retina was visible. Vessels showed leakage in OU | Vitrectomies with subsequent intravitreal dexamethasone implants OU; intravenous methylprednisolone 1 g for 3 days, 500 mg for 2 days, and 100 mg for the final 6 days; local prednisolone acetate hourly and ofloxacin QID; oral cortisone therapy | No renewal of inflammation and subsequently VA stabilized OU at 0.32 |
| Leclaire, 202138 | 1 eye | Pain and visual deterioration | BCVA decreased to 1/15 m (from 0.4), AC cells, deposits on the endothelium, vitreous opacities, perivascular leakage, nonperfused areas, and vascular occlusions | Intravenous prednisolone 80 mg daily | AC and vitreous cleared, BCVA improved to 0.125, and perivascular ischemia was visible over the vascular arches |
| Maruko, 202123 | 12 eyes of 12 patients | — | IOI consisting of AC cells and/or vitreous cells (12 eyes), with IOI + RV in 4 eyes and IOI + RV + RO in 2 eyes. RO was located outside the vascular arcades | IOI was treated with 0.1% betamethasone eye drops; RV was treated with sub-Tenon injection of triamcinolone acetonide 20 mg | VA decreased from 74 ETDRS letters to 35, then improved to 65 in 1 eye with RO. VA decreased from 59 letters to 50, then recovered to 65 in the other eye with RO |
| Narayanan, 202139 | 1 eye | Loss of vision, mild pain, redness | VA reduced to HM (from 20/250), minimal conjunctiva congestion, no lid edema, and 1-mm hypopyon, intense vitritis. Microbiological testing and polymerase chain reaction were negative | Topical steroids administered hourly, vitrectomy biopsy with intravitreal ceftazidime and vancomycin, topical moxifloxacin 6 times daily, prednisolone acetate hourly, and homatropine eye drops TID | Inflammation resolved significantly, and fundus details were visible. No evidence of vasculitis. VA improved to 20/600 |
| Riedel, 202131 | 2 eyes of 1 patient | VA reduced to 0.2 OD (from 0.5) and HM OS (from 0.63) | Vitreous cells, papilledema, thin partly white arteries, cotton-wool spots, bleeding along vessels, highly reflective band in the outer plexiform layer, delayed retinal filling, prolonged arteriovenous passage time, and vascular occlusion | Oral prednisolone 50 mg, oral esomeprazole 40 mg, dexamethasone drops QID, and dorzolamide hydrochloride drops BID. OS also received intravitreal dexamethasone through implant | VA improved to 0.5 OD and 1/35 of a meter OS |
AC, anterior chamber; BCVA, best-corrected visual acuity; BID, 2 times per day; ETDRS, Early Treatment Diabetic Retinopathy Study; FA, fluorescein angiography; HM, hand motion; IOI, intraocular inflammation; IRF, intraretinal fluid; OD, right eye; OS, left eye; OU, both eyes; QID, 4 times per day; RO, retinal vascular occlusion; RV, retinal vasculitis; SRF, subretinal fluid; TID, 3 times per day; VA, visual acuity.