Occlusive Vasculitis Following Intravitreal Rituximab Injection for Primary Vitreoretinal Lymphoma.

PURPOSE: We report three cases of occlusive vasculitis following intravitreal rituximab therapy for biopsy-proven primary vitreoretinal lymphoma (PVRL), one of which was following an injection of the biosimilar Riabni (rituximab-arrx, AmGen) and two of which were following an injection of Rituxan (rituximab, Genentech). METHODS: Case series. RESULTS: Three cases of occlusive vasculitis confirmed with fluorescein angiography are reported 5 days, 8 days, and 3.5 weeks following intravitreal injection of rituximab. The initial vision was poor (20/500, 20/150, and light perception), but vision recovered to baseline in two cases, and remained poor in the case of combined artery and vein occlusion. CONCLUSION: Occlusive vasculitis is a rarely reported but potential complication of intravitreal rituximab therapy in patients who have been previously treated with the agent and may have delayed onset. A low threshold for fluorescein angiography as a diagnostic test for post-injection vision loss and prompt treatment with topical and/or oral steroids should be considered.

Various Ocular Manifestations in Systemic Lupus Erythematosus: A Case Series.

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disorder with various systemic and ocular clinical manifestations. In patients with SLE, central retinal vein and artery occlusion, choroidopathy, and occlusive vasculitis are among the most significant and clinically relevant ocular manifestations, although they do not commonly occur. We present a case series of three SLE patients of different races and genders who developed ocular-related clinical features of SLE during the course of their systemic disease. The clinical outcomes of each patient were different, affecting their vision in bilateral eyes, with some patients having better visual recovery while others having permanently poor vision. These outcomes were not significantly related to the patients' age, gender, or race.

Retinal vasculitis following intravitreal pegcetacoplan administration.

Purpose: To describe a case of retinal vaso-occlusive vasculitis with associated lid edema and conjunctivitis following intravitreal pegcetacoplan administration in a patient with geographic atrophy (GA). Observation: A 78 year old Caucasian woman presented with complaints of lid edema, conjunctival injection, loss of vision, and mild ocular discomfort eleven days after receiving an intravitreal pegcetacoplan injection in the left eye for geographic atrophy. Visual acuity on presentation was decreased to 20/400 from 20/200 previously in that eye. Eyelid edema and conjunctival injection were present with minimal anterior chamber reaction. Dilated fundus examination revealed hemorrhages throughout the retina and signs of retinal vasculitis. The patient subsequently developed hyphema and vitreous hemorrhage. Laboratory evaluations for common infectious and inflammatory causes including aqueous and vitreous cultures for bacteria and Herpes simplex PCR were normal or negative. A delayed hypersensitivity to pegcetacoplan was suspected and was treated with topical, oral subconjunctival and intravitreal steroids. Conclusion: This index report illustrates a case of retinal vaso-occlusive vasculitis associated with intravitreal pegcetacoplan associated with lid edema and conjunctival injection and subsequent hyphema and vitreous hemorrhage. Therapy with steroids topically, systemically, periocularly and intravitreally were used to treat the inflammatory process and prevent further visual loss.

Retinal arterial occlusive vasculitis after multiple intravitreal brolucizumab injections for diabetic macular edema.

Purpose: To describe a case of unilateral retinal arterial occlusive vasculitis after multiple intravitreal brolucizumab (IVBr) treatments for diabetic macular edema (DME). Observations: A 68-year-old Japanese woman who had a 3-year history of insulin-dependent diabetes mellitus presented with decreased vision in the right eye (oculus dexter, OD). After two consecutive IVBr (3 mg) treatments for DME, spaced 6 weeks apart, her best corrected visual acuity improved from 20/32 to 20/28 OD, as central macular thickness (CMT) decreased from 368 µm to 253 µm on optical coherence tomography (OCT). Immediately after the 3rd IVBr, the right intraocular pressure (IOP) increased. One week later, iritis (aqueous flares: 65.0 photon count [PC]/ms) was observed, followed by localized vasculitis 2 weeks later. One month after the 3rd IVBr, extensive vasculitis and vasculitis occluding retinal arterioles were identified. Based on the history of IVBr use and clinical findings, intraocular inflammation (IOI) and subsequent retinal arterial occlusive vasculitis due to IVBr was diagnosed. Topical steroid administration (i.e., eye drops and subtenon injection) resulted in improvement of IOI after 3 months. She subsequently underwent two intravitreal aflibercept injections for DME and panretinal photocoagulation (PRP) to prevent the development of proliferative changes due to diabetic retinopathy. One year after the diagnosis of retinal arterial occlusive vasculitis, the patient had slight loss of vision (20/50) compared to baseline, due to the progression of cataracts, and OCT angiography (OCTA) showed extensive non-perfusion area on the temporal side. However, other examination findings (IOP: 16 mmHg, aqueous flares: 30.5 PC/ms, CMT: 283 µm) were stable. Conclusions and importance: Diagnosis and treatment at a relatively early stage after the onset of IOI prevented severe visual impairment in this case. Topical betamethasone eye drops reduced anterior chamber inflammation associated with IVBr; however, vascular sheathing worsened when topical drops alone was used. Occlusive retinal vasculitis, diagnosed with fluorescein angiography (FA) and OCTA, appeared to stabilize when subtenon triamcinolone injection was added to topical steroid administration. Because the central macula was not involved, severe vision loss was prevented. It is unknown if topical steroid administration would be adequate to prevent worsening of occlusive vasculitis in other cases. Although not used in this case, oral prednisone is one treatment option that may prevent severe vision loss. However, it requires monitoring of side effects, such as elevated blood glucose levels. PRP is also an option in cases where progression of proliferative changes is a concern, as was done in this case. With these considerations in mind, it is important to diagnose brolucizumab-associated IOI and subsequent retinal arterial occlusive vasculitis in DME patients early and initiate treatment to prevent severe visual impairment. Diagnosing new IOI and subsequent retinal arterial occlusive vasculitis is more difficult in DME than in neovascular age-related macular degeneration because of the inflammatory component often associated vascular occlusions. Therefore, early IOI diagnosis and follow-up using various instruments such as laser flare cell meter, wide-field color imaging, OCT/OCTA, and FA, in addition to usual comprehensive ophthalmologic examinations, is crucial.

Acute retinal necrosis: clinical features, management and outcomes.

PURPOSE: To evaluate the clinical features, treatment, and visual outcome of patients with acute retinal necrosis (ARN). METHODS: The data of patients were retrospectively reviewed. Factors associated with visual loss and factors affecting the risk for retinal detachment (RD) development were evaluated. RESULTS: Twenty-four eyes of 24 patients (7 female/17 male, mean age 43.7 years, mean follow-up period 31.0 months) were included. In ocular fluid samples of 15 (83%) out of 18 eyes, polymerase chain reaction (PCR) tests were positive for herpes simplex virus (seven eyes; 39%), varicella zoster virus (six eyes; 33%), cytomegalovirus (one eye; 6%), and adenovirus (one eye; 6%). Central retinal occlusive vasculitis was observed in three (13%) eyes. Systemic antiviral therapy was given to all patients, and additional intravitreal ganciclovir was administered in seven eyes (29%). The most common complication was RD (46%). There was no statistically significant difference in the frequency of RD between herpes simplex virus- and varicella zoster virus-positive patients (p = .617). The rate of RD was similar in eyes undergoing prophylactic laser photocoagulation (LPC), eyes undergoing vitrectomy + LPC, and eyes not undergoing LPC (p = .237). The number of eyes with final visual acuity below 20/200 was significantly higher in eyes with RD than without RD (p = .047). CONCLUSION: Prophylactic LPC and vitrectomy did not show clear benefits in terms of preventing RD development. RD was the most common complication and a major factor for a poor visual prognosis.

CMV Retinitis with Panretinal Occlusive Vasculitis.

PURPOSE: To report the clinical features of cytomegalovirus (CMV) retinitis with panretinal occlusive vasculitis. METHODS: Retrospective case series. RESULTS: Four eyes in 3 non-HIV patients (male: female = 3:0) were included. Previous medical history included diabetes mellitus (n = 2), age-related macular degeneration (n = 1), and Multiple myeloma under chemotherapy (n = 1). All patients were treated with oral valganciclovir and intravitreal ganciclovir. Slow resolution of retinitis related retinal opacification was noted in all 4 eyes. Two eyes had anti-viral agents discontinued despite the persistent retinitis related opacification and the lesions slowly resolved in the following months. The final decimal visual acuity was equal to or worse than 0.02 in 3 of the 4 eyes. CONCLUSION: In eyes of CMV retinitis with panretinal occlusive vasculitis, rapid resolution of retinitis lesions is an unreliable sign evaluating the therapeutic efficacy of anti-viral agents. Besides, despite treatment of anti-viral agents, deteriorating vascular occlusion may further endanger macular function.

Swept-source optical coherence tomography angiography of retinal occlusive vasculitis following brolucizumab administration: a case report.

BACKGROUND: We present a case of retinal occlusive vasculitis following brolucizumab administration and the first report of optical coherence tomography angiography (OCTA) findings after treatment. CASE PRESENTATION: A 71-year-old man complained of vision loss in the left eye 6 weeks after brolucizumab injection. His visual acuity was counting fingers, and examination revealed 1 + anterior chamber cells with 2 + vitreous cells. Fundus examination demonstrated vitreous haze, retinal whitening, and vascular sheathing. Fluorescein angiography revealed filling defects in the retinal arteries and veins, and OCTA showed extensive capillary nonperfusion. Under the diagnosis of brolucizumab-associated intraocular inflammation (IOI) and retinal occlusive vasculitis, topical, sub-Tenon, and systemic corticosteroids were administered. After the treatment, visual acuity improved to 20/200, and OCTA revealed gradual improvement in capillary dropout; however, with the limited improvement of reperfusion in the perifoveal areas. CONCLUSIONS: Prompt evaluation and intensive corticosteroid treatments are required for brolucizumab-associated IOI. OCTA imaging provides detailed information on microvascular changes in the retinal vascular plexuses in brolucizumab-associated retinal occlusive vasculitis.

Chickenpox Associated Retinitis and Occlusive Vasculitis in a Vaccinated Child: A Case Report and Literature Review.

Either retinitis and occlusive vasculitis are rare but vision threatening ocular complications of chickenpox in children. In this case report a 13-year-old girl who developed chickenpox 2 days before complaining with visual loss in her right eye is presented. She was vaccinated one dose of varicella zoster virus (VZV) vaccine when she was 12 months old. Best corrected visual acuity was counting fingers at 1.5 m in right eye. A subtle anterior segment inflammation and mild vitritis were observed. Fundoscopic examination of right eye showed ischemia in paracentral macula and white foci of retinitis along the superotemporal branch of retinal vessels. She was hospitalized and intravenous acyclovir treatment at 3 × 10 mg/kg daily dose was started. Serum IgM and IgG for VZV were positive. Aqueous humor PCR test was also reported positive for VZV DNA. Oral methylprednisolone was added at a dose of 64 mg/day at the 3rd day acyclovir treatment. Macular edema developed at 4th week of treatment and bevacizumab was administered intravitreally. After 3 injections retinal edema subsided completely. At 6-month follow-up retinal ischemia in superotemporal periphery was observed and photocoagulation was added to treatment.

Appendicitis and COVID: cause or effect?

Background: Vasculitis and phlebitis with vascular occlusion within appendix specimen is rare. Several authors have reported COVID-19 related veno-occlusive disease in hepatic pathology, but lymphoid aggregation with phlebitis is unusual in appendix specimen. We present a case with medium size venule phlebitis in an appendix of a patient recovered from COVID-19 infection. Case presentation: A 27-year-old who recently recovered from COVID-19 infection 12 weeks prior, presented with acute appendicitis, confirmed on computed tomography and operative findings. He underwent an uneventful laparoscopic appendicectomy. Histopathology showed veno-occlusive vasculitis within the appendix specimen. Conclusions: Veno-occlusive disease within the appendix is uncommon. Emerging data suggest COVID-19 infection can cause systemic vascular complications. We herein report a case of healthy patient with no past medical history with an unusual findings of medium vessels phlebitis within the appendix post COVID-19 infection.

Idiopathic Retinitis, Vasculitis, Aneurysms, and Neuroretinitis (IRVAN): Early Treatment Saves Sight.

We report a rare case of bilateral Idiopathic Retinitis, Vasculitis, Aneurysms, and Neuroretinitis (IRVAN) with occlusive vasculitis. A 28-year-old female presented with sudden decreased vision in her left eye for three days. Visual acuity in the right eye was 6/6, whereas it was 6/9 in the left eye. The anterior segment was examined and found to be normal. A fundus examination of the right eye showed an arteriolar aneurysm on the optic disc, vascular sheathing, and generalized retinal pigment epithelial atrophy. The left eye was in worse condition, with a swollen optic disc, disc hemorrhage, multiple arteriolar aneurysms, hard exudates at the peripapillary and macular region, peripheral vasculitis, neovascularization, and vitreous hemorrhage. Optical coherence tomography revealed mild cystoid macula edema (CME) in both eyes. Fluorescein angiography of both eyes demonstrated arteriolar aneurysms, vascular leakage, and peripheral ischemia. There was additional leakage from new vessels and masking secondary to vitreous hemorrhage in the left eye. The results of the systemic evaluation and extensive laboratory testing were negative. She had bilateral retinal photocoagulation and was administered oral prednisolone later with slow tapering due to increasing CME. Her eye condition did not worsen, and she maintained good vision in both eyes. IRVAN, even though rare, should be suspected in patients with occlusive vasculitis, arteriolar aneurysm, and macula exudation. Since the nature of the disease is more aggressive than other ischemic retinopathies, early detection, intervention, and close follow-up are crucial to prevent rapid visual loss.

Bilateral Occlusive Retinal Vasculitis in a Patient with Dermatomyositis.

A 48-year-old woman with a history of dermatomyositis (DMS) presented with 2 weeks of worsening myalgias, weakness, and diffuse edema following cessation of her systemic immunosuppression and subsequently developed severe bilateral vision loss consistent with bilateral frosted branch angiitis. Multimodal imaging was performed, and the patient was successfully treated with pulse-dose steroids and intravenous immunoglobulin, as well as intravitreal aflibercept. Ophthalmic involvement of DMS is typically limited to episcleritis, conjunctivitis, and uveitis. We present an uncommon case of bilateral occlusive retinal vasculitis with frosted branch angiitis in a patient with DMS. The significant improvement anatomically and in visual acuity in our patient suggests a role of combined anti-vascular endothelial growth factor and systemic immunosuppression in the management of DMS -related frosted branch angiitis. We suggest that retinal vasculitis should be considered in patients with known DMS and acute vision loss, with prompt referral for ophthalmologic evaluation.

Toxic Posterior Segment Syndrome Presenting as Occlusive Retinal Vasculitis following Vitreoretinal Surgery.

PURPOSE: To report a rare retinal manifestation of toxic posterior segment syndrome following vitreoretinal surgery. METHODS: In this case series, we report three cases of rhegmatogenous retinal detachment for which pars plana vitrectomy with silicone oil injection was done. All three patients developed an intense anterior chamber reaction along with occlusive vasculitis-like fundus picture. RESULTS: The three patients were started on topical and systemic steroids, and there was a dramatic improvement in vision and clinical signs at postoperative week 1. CONCLUSION: Toxic posterior segment syndrome is a sight-threatening complication after vitreoretinal surgery, but responds well to topical and systemic steroids.

A child with a rare presentation of ocular bartonellosis.

A 6-year-old boy was referred from the optometrist for bilateral painless blurred vision of 2 weeks duration during routine screening. Upon examination, best-corrected visual acuity was 20/200 (right eye) and 20/120 (left eye). Anterior segment examination was normal for both eyes. Funduscopy showed bilateral optic disc swelling with peripapillary exudates and diffuse retinochoroiditis involving the posterior pole. Optical coherence tomography revealed diffuse retinal thickening with intraretinal fluids and cystoid changes of central fovea. Fluorescein angiography showed bilateral hot discs with vasculitis in all quadrants and large areas of nonperfusion at peripheral retina. The patient was initially treated as presumed ocular tuberculosis (TB) based on clinical presentation and history of contact with family member having pulmonary TB. Antituberculous therapy was started and both eyes received panretinal laser photocoagulation. After 3 weeks of anti-TB treatment, serology for Bartonella turned out to be positive. Treatment was changed to intravenous ceftriaxone for 10 days followed by oral cotrimoxazole for 6 weeks and combined treatment with oral prednisolone. Gradual clinical improvement was seen with corresponding visual gain due to the reduction of macular edema, but residual thickening remained due to its chronicity.

Risk of Inflammation, Retinal Vasculitis, and Retinal Occlusion-Related Events with Brolucizumab: Post Hoc Review of HAWK and HARRIER.

PURPOSE: An independent Safety Review Committee (SRC), supported by Novartis Pharma AG, analyzed investigator-reported cases of intraocular inflammation (IOI), endophthalmitis, and retinal arterial occlusion in the phase 3 HAWK and HARRIER trials of brolucizumab versus aflibercept in neovascular age-related macular degeneration (nAMD). DESIGN: A post hoc analysis of a subset of data from two 2-year, double-masked, multicenter, active-controlled randomized phase 3 trials (NCT02307682, NCT02434328). PARTICIPANTS: Patients (N = 1817) with untreated, active choroidal neovascularization due to age-related macular degeneration in the study eye were randomized and treated in HAWK/HARRIER. The SRC reviewed data from cases of investigator-reported IOI (60/1088 brolucizumab-treated eyes; 8/729 aflibercept-treated eyes). METHODS: The SRC received details and images (color fundus photography, fluorescein angiography, and OCT) for all investigator-determined cases of IOI, retinal arterial occlusion, and endophthalmitis. Cases were reviewed in detail by ≥2 readers, then adjudicated by the SRC as a group. MAIN OUTCOME MEASURES: Within this patient subset: incidence of IOI, signs and incidence of retinal vasculitis and/or retinal vascular occlusion, and visual acuity loss; time since first brolucizumab injection to IOI event onset; and frequency of visual acuity loss after brolucizumab injection by time of first IOI event onset. RESULTS: Fifty brolucizumab-treated eyes were considered to have definite/probable drug-related events within the spectrum of IOI, retinal vasculitis, and/or vascular occlusion. On the basis of these cases, incidence of definite/probable IOI was 4.6% (IOI + vasculitis, 3.3%; IOI + vasculitis + occlusion, 2.1%). There were 8 cases (incidence 0.74%) of at least moderate visual acuity loss (≥15 ETDRS letters) in eyes with IOI (7 in eyes with IOI + vasculitis + occlusion). Of the 8 cases, 5 experienced their first IOI-related event within 3 months of the first brolucizumab injection (increasing to 7/8 within 6 months). Incidence of IOI in aflibercept-treated eyes was 1.1%, with at least moderate visual acuity loss in 0.14%. CONCLUSIONS: This analysis of IOI cases after brolucizumab injection identified signs of retinal vasculitis with or without retinal vascular occlusion and an associated risk of visual acuity loss. The findings will help physicians to evaluate the risks and benefits of brolucizumab treatment for nAMD.

Management Strategies of Acute Retinal Necrosis: Current Perspectives.

Acute retinal necrosis is a rare yet devastating disease, with significant ocular morbidity. Over the past several decades, initial treatment regimens have shifted from intravenous antivirals requiring hospital admission to the routine use of oral antivirals with intravitreal antivirals for immediate local control. Given the rarity of this disease process and a lack of large-scale research trials, debate continues over recommended practice guidelines. In this paper, we review current diagnostic criteria and recommend a treatment algorithm based on available evidence.

Lymphoma masquerading as occlusive retinal vasculitis: A case study.

PURPOSE: To describe a case of retinal lymphoma presenting as an occlusive retinal vasculitis without vitritis that was exquisitely responsive to intravitreal dexamethasone implant (IVDI). OBSERVATION: A 66-year old male presented with decreased vision in the right eye and was diagnosed with occlusive retinal vasculitis and prominent cystoid macular edema though he lacked vitritis. A complete systemic workup for infectious, inflammatory, and infiltrative etiologies was unremarkable. Intravenous methylprednisolone and cyclophosphamide had no clinical effect. Due to persistent perivascular exudates and refractory macular edema, IVDI was administered with marked improvement in vision and clinical findings. Subsequent retinal vasculitis in the left eye responded to IVDI as well. The patient remained disease free for months while on weekly adalimumab. He then presented with acute vision loss in the left eye due to a lymphomatous subretinal infiltration and a new lesion in the corpus callosum. He has remained disease free for more than two years after intravitreal methotrexate injections and rituximab with an autologous stem cell transplant. CONCLUSION AND IMPORTANCE: Lymphoma may present as an occlusive retinal vasculitis without vitritis and can be masked due to its response to IVDI.

Severe vision loss secondary to retinal arteriolar occlusions after multiple intravitreal brolucizumab administrations.

PURPOSE: To describe a case of unilateral retinal arteriolar occlusion following multiple intravitreal brolucizumab injections for neovascular age-related macular degeneration (nAMD). OBSERVATIONS: A 92-year-old Caucasian woman presented with blurry vision in her left eye (OS) after receiving the third dose of intravitreal brolucizumab. At the time of presentation, visual acuity (VA) was 20/40 in her right eye (OD) and had decreased from 20/150 to count finger (CF) at 1-foot OS. On examination, there was no evidence of active inflammation in the anterior chamber OU. Dilated fundus examination showed no vitritis in OD and 1+ vitreous cells OS, flame-shaped hemorrhage at the superior optic disc margin, and retinal whitening surrounding the proximal portion of the supero-temporal branch of the central retinal artery. There were drusen in OS and retinal pigment epithelial (RPE) changes in the maculae of OU. Intra-arteriolar greyish deposits were seen OS. Fluorescein angiography (FA) showed hyper-fluorescence in the maculae corresponding to fibrovascular pigment epithelial detachments (PED) OU. No peri-vascular leakage was noted OU. Delayed filling of multiple arterioles in early and late phases OS was observed on FA. The patient was diagnosed with retinal arteriolar occlusion associated with repeated intravitreal brolucizumab administrations. CONCLUSION: Retinal arteriolar occlusion with severe vision loss, possibly secondary to inflammatory responses, can occur after subsequent intravitreal brolucizumab injections, even if no inflammation occurred after initial administrations. Vaso-occlusive disease should be considered as a potential ocular complication, with acute as well as delayed onset, following intravitreal brolucizumab therapy.

Retinal arterial occlusive vasculitis following intravitreal brolucizumab administration.

PURPOSE: To describe retinal arterial occlusion and vasculitis following intravitreal brolucizumab administration in a patient with neovascular age-related macular degeneration (nAMD). OBSERVATION: An 88-year-old Caucasian woman with neovascular age-related macular degeneration (nAMD) complained of painless loss of vision with light sensitivity in both eyes (OU) four weeks after bilateral intravitreal brolucizumab. Upon examination, her visual acuity decreased to 20/40 in the right eye (OD) and 20/50 in the left eye (OS). Examination revealed 0.5+ and 1+ anterior chamber cells in OD and OS, respectively. The patient was treated with 1% prednisolone acetate eyedrops in both eyes, and after several weeks, the anterior chamber cells resolved. However, the patient still reported a decline in visual acuity (VA). Fluorescein angiography (FA) revealed retinal arterial occlusion, vasculitis, and optic nerve inflammation in the left eye. Retinal intra-arterial grayish materials were also detected. Laboratory evaluations were performed for common infectious and inflammatory causes and were normal or negative. A delayed inflammatory reaction to brolucizumab was suspected as the cause of the ocular inflammation and retinal vasculitis. An intravitreal dexamethasone implant was inserted into the left eye to treat the inflammation. One week after the dexamethasone implant, VA improved to 20/40 in OU; FA showed improvement, but residual peri-vascular leakage remained. CONCLUSION: Medication-associated uveitis is a rare adverse effect that can lead to vision loss. The index report illustrates a case of intraocular inflammation, retinal arterial vaso-occlusion and vasculitis associated with intravitreal brolucizumab. The delay in developing uveitis suggests that the inflammation is due to a delayed hypersensitivity reaction which can occur several days or weeks after administration of the inciting agent. Recently, several cases of uveitis and vasculitis associated with brolucizumab have been presented and those cases have similar features compared to the index case (1). Therapy with steroids (either intraocular or systemic), after infectious etiologies have been excluded, may be beneficial in halting inflammation and preventing further vision loss.