Intraocular inflammation and presumed retinal vasculitis following initial pegcetacoplan intravitreal injection

Summary

We report a case of presumed retinal vasculitis and precipitous complete vision loss following a single intravitreal injection of pegcetacoplan. A 76-year-old woman received intravitreal pegcetacoplan in the right eye for geographic atrophy. Visual acuity was 20/50 right eye. Ten days after the injection, she experienced initial signs of subjective vision loss. On day 11, she presented with elevated intraocular pressure and visual acuity of hand motions, worsening to no light perception (NLP) by day 12. Anterior chamber and vitreous fluid taps for Gram stain and culture were negative. On day 22, the patient had diffuse retinal hemorrhages along a retinal vascular distribution. At day 83, visual acuity remained NLP. This patient developed presumed occlusive retinal vasculitis, progressing from visual acuity of 20/50 to NLP within 2 days of initial subjective vision loss and 12 days of a single intravitreal pegcetacoplan injection.

Introduction

Pegcetacoplan (Syfovre; Apellis, Waltham, MA) was approved for intravitreal injection by the US Food and Drug Administration in February 2023 to treat geographic atrophy (GA) secondary to age-related macular degeneration (AMD).1 In the post-marketing phase, there have been reports of intraocular inflammation and subsequent retinal vasculitis following initial intravitreal pegcetacoplan injections. In January 2024, the American Society of Retina Specialists Research and Safety in Therapeutics (ReST) Committee released a compilation of known cases of retinal vasculitis and occlusive retinal vasculopathy following pegcetacoplan injection.2 The report included 14 eyes of 13 patients with retinal vasculitis after a single injection. Eleven of 14 eyes developed occlusive retinal vasculopathy, and median onset of symptoms was 10.5 days after treatment. Here, we report a patient who experienced such a reaction of presumed retinal vasculitis with precipitous complete vision loss following a single intravitreal injection of pegcetacoplan.

Case Report

A 76-year-old woman presented for bilateral, nonexudative AMD. Fundus examination showed central geographic atrophy and retinal pigment epithelium (RPE) atrophy on ocular coherence tomography (OCT) (Fig‍ure 1). With visual acuity of 20/50 in each eye and intraocular pressure (IOP) of 20 mm Hg in the right eye and 18 mm Hg in the left, the patient received an intravitreal pegcetacoplan injection in the right eye using the standard procedure without complication.

Figure 1.

Imaging collected on initial visit, prior to injection. A, Optical coherence tomography (OCT), macula, showing inner retinal hyperreflectivity, disruption of retinal architecture, retinal pigment epithelium thinning, and choroidal thinning. B, Fluorescein angiography with hyperfluorescent geographic atrophy of the macula.

Ten days after the injection, she developed painless, blurred vision in that eye. On day 11, her visual acuity was hand motions, and IOP was elevated (37 mm Hg). Corneal edema precluded a view of anterior chamber and posterior segment. B-scan ultrasound showed no vitreous opacities or retinal detachment (RD). She started topical prednisolone, brimonidine, dorzolamide/timolol, and oral acetazolamide. On day 12, IOP decreased to 17 mm Hg. Anterior chamber and vitreous taps were performed for Gram stain and culture. Additionally, intravitreal antibiotic injections of 1 mg vancomycin and 2 mg ceftazidime were administered. On day 13, the patient’s visual acuity was no light perception (NLP), and IOP was 8 mm Hg. B-scan ultrasound showed choroidal thickening, minimal vitreous opacities, and no mass or RD (Figure 2).

Figure 2.

B-scan ultrasonography from postinjection day 13. There were no signs of vitritis, masses, or retinal detachment that could have been contributing to the significant vision loss.

On day 22, visual acuity was NLP, and IOP was 20 mm Hg. Anterior chamber examination showed 4+ flare and trace cell. Splotchy hemorrhage on the iris was noted, with prominent iris vessels but no rubeosis. Corneal edema limited the view of the fundus, but diffuse retinal hemorrhages were noted along a retinal vascular distribution. Anterior chamber and vitreous Gram stain and cultures were negative.

On day 34, widefield fluorescein angiography (FA) was attempted, but the view was inadequate to determine retinal vascular detail. OCT showed macular thinning with hyperreflectivity of inner layers suggesting post-ischemic changes.

On day 56, anterior chamber examination showed trace flare and resolution of iris hemorrhages but persistence of prominent iris vessels. OCT again showed macular thinning. (Figure 3).

Figure 3.

OCT macula on day 56 postinjection had poor image quality due to obstructed view to the posterior segment. Macular thinning and hyperreflectivity are indicative of ischemia.

On day 83, visual acuity remained NLP, and IOP was 20 mm Hg and 12 mm Hg in the right and left eyes, respectively. Given persistent elevation of right eye IOP and rubeosis iridis, the patient was diagnosed with early neovascular glaucoma, and intravitreal bevacizumab was administered.

Discussion

We report the case of a 76-year-old patient who experienced sudden, progressive vision loss in her right eye 10 days after intravitreal injection of pegcetacoplan. Our patient’s presentation was similar to those in the report “Retinal Vasculitis After Intravitreal Pegcetacoplan,” released by the ASRS ReST Committee.2 In that publication, 14 of 14 eyes (100%) presented with signs of anterior chamber inflammation, 6 (43%) with corneal edema, and 12 (78%) with retinal hemorrhages. Ten of the 14 eyes (71%) had an IOP increase of >10 mm Hg from baseline to presentation (median IOP increased from 15 mm Hg to 27 mm Hg). Furthermore, 6 eyes (43%) had more than a 6-line decrease in visual acuity from baseline to final follow-up (range, 20/70-NLP). While all eyes had different lengths of follow-up (median, 58 days; range, 15–109 days), only 3 (21%) showed any signs of visual acuity improvement after the initial adverse event.

Our patient had anterior chamber inflammation, corneal edema, retinal hemorrhages, and an increase of 14 mm Hg in IOP following the pegcetacoplan injection. Our case is notable because of the quick progression to NLP vision after symptom onset. The first subjectively perceived indication of vision loss was on post-injection day 10, and by day 12 the patient had no light perception. Strikingly, visual acuity in her right eye decreased from her preinjection acuity of 20/50 to NLP in just 2 days and remained NLP 83 days after the injection.

In patients presenting with vision loss and inflammation following an intravitreal injection, the risk of infectious endophthalmitis must be acknowledged on the differential diagnosis. However, one would typically expect a shorter time course from injection to symptom onset and a more significant anterior chamber reaction with vitritis, unlike what was seen in our patient. Furthermore, anterior chamber and vitreous fluid cultures and Gram stain were negative. At the time of presentation, a central retinal artery occlusion or a vein occlusion were considered as causes of the sudden vision loss but were deemed unlikely due to the extensive inflammatory symptoms, which would be atypical. Angle closure glaucoma was also considered, especially in the context of elevated IOP, but this was ruled out on examination, because the anterior chamber was deep, with no evidence of an unobstructed angle.

Throughout our patient’s clinical course, fundus photographs and FA were attempted several times but served no diagnostic utility given the extremely poor quality from impaired media. Despite the inability to confirm retinal vasculitis on FA, this diagnosis was presumed due to a number of factors. The timing of presentation at 10 days post-injection along with rapid progression to NLP vision is consistent with other reports of vasculitis following pegcetacoplan use. Furthermore, the presence of hemorrhages following a vascular distribution with OCT evidence of inner retinal hyperreflectivity and progressive retinal thinning suggest an inflammatory event with occlusive vasculitis and consequent retinal ischemia. This is further supported by early development of rubeosis, again implying vascular occlusion and ischemia. Following any ocular injection, it is important to keep a broad differential diagnosis, but the unique constellation of symptoms in this case ultimately raised concern for an adverse inflammatory reaction to pegcetacoplan.

There is still much to be discovered regarding the underlying mechanism of retinal vasculopathies secondary to pegcetacoplan. Nahar et al3 present 2 patients who experienced significant vision loss following intravitreal pegcetacoplan injections and ultimately underwent enucleation for pain control. Histopathologic and immunohistochemical examination revealed vascular thromboses, retinal hemorrhages, and dense inflammatory infiltrates primarily composed of T cells, macrophages, and eosinophils. They attribute the constellation of findings to a type IV hypersensitivity reaction, using the term drug-induced, immune-mediated, retinal vasculopathy and choroiditis (DIRVAC) to describe the condition.3 Rare adverse reactions do not substantiate drug-related toxicity or negate the potential benefits of pegcetacoplan for many patients with AMD.1,4 However, it should be noted that this medication is relatively new, and its effects continue to be studied in the general population. Ophthalmologists should take extra care to discuss risks and benefits with patients during the informed consent process. Furthermore, continued reporting of like cases to the ASRS ReST Committee may improve the data surrounding this topic, allowing better counseling of patients in the future.