Hemorrhagic Occlusive Retinal Vasculitis Research Articles

Retinal vasculopathy and choroiditis after pegcetacoplan injection: clinicopathologic support for a drug hypersensitivity reaction

PurposeTo report the detailed histopathology of two enucleated eyes from two patients who developed severe visual loss associated with retinal hemorrhages, vessel sheathing and vascular nonperfusion after administration of an initial dose of intravitreal pegcetacoplan, and to propose, with supportive histopathology, the pathogenesis of the clinical syndrome previously termed hemorrhagic occlusive retinal vasculitis (HORV). DesignCase series. SubjectsTwo enucleated eyes from two patients treated with intravitreal pegcetacoplan. MethodsRetrospective, multicenter consecutive clinical-pathologic analysis. Main Outcome MeasuresHistopathologic review and immunophenotypic characterization. ResultsBoth patients presented with inflammation and significant vision loss nine days following the initial injection of pegcetacoplan with no subsequent improvement and underwent enucleation for pain control. Histologic examination of the enucleated eyes (patient one at 4 months post-injection and patient two at 40 days) revealed extensive vascular thrombosis, retinal hemorrhages and necrosis, and a dense inflammatory infiltrate in the uvea and variably the optic nerve, episclera, and muscle tendons composed of predominantly of T-cells, macrophages, and eosinophils. Notably, the inflammatory infiltrate was absent from the retina. In addition, one eye demonstrated multiple foci of glomerular-like vascular proliferations in the uveal tract and thrombosis with focal recanalization of vessels in the optic nerve. ConclusionDrug-induced, immune-mediated, retinal vasculopathy and choroiditis (DIRVAC) is a rare complication following pegcetacoplan injection. Although some limitations arise in interpretation of histopathologic findings due to compensatory changes in the eyes over time (prior to enucleation), the authors propose that the combined clinical, histopathologic, and immunohistochemical findings suggest a mixed-type, delayed hypersensitivity reaction as mechanism of initial injury.

Update on Retinal Drug Safety: Proceedings of the ASRS ReST Committee Webinar Part 1.

Purpose: To review the first Research and Safety in Therapeutics (ReST) Committee webinar and summarize the most current recommendations regarding diagnosis and management. Methods: The ReST Committee is comprised of members of the American Society of Retina Surgeons (ASRS). At regular internal meetings, safety issue reports from the website are reviewed. A webinar series was started in 2021 to update members on multiple relevant potential safety events. Results: Topics reviewed in the webinar included pentosan polysulfate sodium (Elmiron) maculopathy, intraocular pressure elevation reported with the aflibercept prefilled syringe (PFS), and brolucizumab-associated inflammation with occlusive retinal vasculitis. Retinal toxicity related to intraoperative medications was reviewed, including hemorrhagic occlusive retinal vasculitis after intraocular vancomycin, dilution errors with intravitreal aminoglycosides, inadvertent overdoses of cefuroxime after cataract surgery, and toxic posterior segment syndrome after dropless cataract surgery using compounded triamcinolone-moxifloxacin. Indocyanine green toxicity has been reported after its use as an adjuvant during macular hole surgery. Conclusions: The past decade has seen advances in retinal pharmaceuticals and drug-delivery devices. The ASRS ReST Committee collects data from its website reporting system to inform members about up-to-date pharmaceutical and device safety concerns. Recently, a webinar was used to inform members of pigmentary maculopathy associated with pentosan polysulfate sodium, safety regarding the aflibercept PFS, intraocular inflammation and occlusive retinal vasculitis secondary to brolucizumab, and retinal toxicity from intraoperative ocular medications.

Efficacy and safety of large-scale use of vancomycin injection in infusion bottle during vitreoretinal procedures.

The purpose of this study was to assess the safety and efficacy of large-scale use of vancomycin injection in an infusion bottle during vitreoretinal procedures. This was a retrospective evaluation of all vitreoretinal procedures done in the last 70 months, where intraoperatively vancomycin injection (0.2 mg/mL) was used in an infusion bottle prophylactically as standard care. Vitreoretinal procedures were categorized as major (duration >30 min), minor (duration <30 min), and silicone oil removal. Postoperatively, a detailed ocular examination was done to rule out hemorrhagic occlusive retinal vasculitis (HORV) or signs of postoperative bacterial endophthalmitis. Over the last 70 months, a total of 31,720 vitreoretinal procedures were performed, which included 24,371 major vitreoretinal procedures, 1401 minor vitreoretinal procedures, and 5948 silicone oil removal cases. None of these cases developed HORV or bacterial endophthalmitis. Vancomycin (0.2 mg/mL) in infusion fluid during vitreoretinal procedures is safe and can be advocated as a prophylactic measure against postvitrectomy bacterial infections.

Intracameral Drug Delivery: A Review of Agents, Indications, and Outcomes.

An intracameral (IC) injection directly delivers the drug into the anterior chamber of the eye. This targeted drug delivery technique overcomes the ocular barriers and offers a high therapeutic concentration of medication at the desired site and consequently better clinical outcomes. IC drug delivery is a safe and effective modality with many advantages over topical delivery. These include excellent bioavailability, reduced systemic risk, and minimal ocular toxicity. Agents delivered via IC injection have shown promising results against infection, inflammation, ocular hypertension, and neovascularization. Current literature shows that IC antibiotics, including cefuroxime, vancomycin, and moxifloxacin, are routinely used for prophylaxis of endophthalmitis. Other drugs available for IC use are steroids, anesthetics, mydriatics, miotics, antivascular endothelial growth factor, antiglaucoma, and alkylating agents. Introduction of sustained-release devices containing dexamethasone or Bimatoprost in anterior chamber via IC route has the potential in treating ocular inflammation and raised intraocular pressure. The complications such as hemorrhagic occlusive retinal vasculitis and toxic anterior segment syndrome have been documented with IC prophylaxis but are rare. In this review, we provide an overview of available IC drugs, their pharmacokinetics, the spectrum of activity, dosage and preparation, prophylactic and therapeutic usage, clinical efficacy, and safety profiles.

Vancomycin-Associated Hemorrhagic Occlusive Retinal Vasculitis: A Case Series and Systematic Review.

This study describes three unilateral cases of hemorrhagic occlusive retinal vasculitis (HORV) after cataract surgery and a review of the literature until February 2022, including 21 articles reporting HORV cases. Altogether, 61 eyes (41 patients) were included. Twenty patients had bilateral and 21 patients had unilateral HORV. Prophylactic vancomycin was given to all patients. Additional vancomycin use was associated with the worst outcome. The mean time to HORV was 9 days post-cataract surgery. In bilateral cases, the median time between surgeries was 7 days. Visual acuity was < 20/400 in 48%, with no light perception in 20%. Neovascular glaucoma developed in 43%. Central macular thickening or hyperreflectivity of the inner retinal layers on optical coherence tomography was associated with worse outcomes. Corticosteroid treatment, early panretinal laser photocoagulation, or anti-vascular endothelial growth factor therapy, and prophylaxis alternative to vancomycin is recommended. [Ophthalmic Surg Lasers Imaging Retina 2022;53:702-712.].

Hemorrhagic Occlusive Retinal Vasculitis Associated With Triamcinolone-Moxifloxacin Use During Uncomplicated Cataract Surgery

This case series describes the outcomes of cataract extraction with intraocular lens placement in 2 patients.

Complications of intravitreal injections: 2022.

This review highlights the complications of both intravitreal injection procedure as well as different intravitreal medications including antivascular endothelial growth factors, antibiotics, antivirals, antifungals, methotrexate, and steroids. Techniques for reducing rates of endophthalmitis will also be discussed. Intravitreal vancomycin can cause hemorrhagic occlusive retinal vasculitis resulting in severe vision loss. Intravitreal brolucizumab is associated with intraocular inflammation and retinal vasculitis resulting in significant vision loss. Face mask use by both patient and physician is not associated with increased risk of endophthalmitis and may decrease culture positive endophthalmitis. Intravitreal injections continue to be one of the most commonly performed procedures by ophthalmologists. Although the injections are generally well tolerated, sight-threatening complications can occur including endophthalmitis, retinal detachment, and/or retinal vasculitis. Adverse events associated with specific medications are outlined below. Several safety measures have been shown to reduce rates of endophthalmitis, the most concerning complication of this procedure.

Outcomes of 27gauge pars plana vitrectomy for a variety of posterior segment diseases.

To report outcomes of 27 gauge pars plana vitrectomy for the management of a variety of simple to complex posterior segment disorders. This retrospective cohort study was conducted at the Shifa International Hospital, Islamabad, Pakistan, and comprised data of all patients who underwent 27 gauge pars plana vitrectomy between July 1, 2015, and June 30, 2019, for a variety of indications. Data noted included age, gender, laterality, diagnosis, pre-operative visual acuity, date of surgery and surgical details, including operating time and complications. Best corrected visual acuity at 3 months was also recorded. Data was analysed using SPSS 21. Of the 574 patients, 355(62%) were males and 219(38%) were females. The overall mean age was 55±16.9 years. There were total 665 eyes as 91(15.8%) patients underwent bilateral surgeries. The most common surgical indications were diabetic tractional retinal detachment 196(29.5%) and vitreous haemorrhage 191(28.7%). Mean operating time was 62± 37 minutes. With the exception of 0.34% cases where 20 gauge fragmatome was used, no case required conversion to 20 gauge system, while 25 gauge trocar was used for silicon oil injection. Per-operative complications included iatrogenic retinal tear 2(0.3%) eyes and supra choroidal silicon oil migration 1(0.15%) eye. Post-operative complications were raised intraocular pressure 7(1.05%), endophthalmitis 1(0.15%) eye, haemorrhagic occlusive retinal vasculitis 1(0.15%) eye and rhegmatogenous retinal detachment 2(0.3%) eyes. Mean best corrected visual acuity improved from 1.62± 0.68 to 0.4± 0.38 logarithm of minimum angle of resolution (p<0.001). The 27 gauge pars plana vitrectomy was found to be a safe and effective procedure for both simple and complex retinal pathologies requiring significant surgical manipulation.

Cefuroxime-Related Hemorrhagic Occlusive Retinal Vasculitis After Cataract Surgery

Cefuroxime-Related Hemorrhagic Occlusive Retinal Vasculitis After Cataract Surgery

Successful Clinical Outcome of Vancomycin-induced Hemorrhagic Occlusive Retinal Vasculitis

ABSTRACT We present a case of a patient that experienced severe hemorrhagic occlusive retinal vasculitis secondary to injection of 1.0 mg/0.1 ml of intracameral vancomycin for endophthalmitis prophylaxis after an uneventful cataract surgery. The case is especially unique in that our patient ended up maintaining 20/25 vision with an ocular disease that is typically visually threatening. This may be due to the aggressive administration of periocular and oral steroids combined with scheduled anti-VEGF injections that were later transitioned into a treat and extend regimen.

Toxicities of and inflammatory responses to moxifloxacin, cefuroxime, and vancomycin on retinal vascular cells

Prophylactic intracameral injection of antibiotics is commonly used to prevent endophthalmitis after cataract surgery. However, devastating visual complications have been reported including hemorrhagic occlusive retinal vasculitis (HORV).To determine the toxic and inflammatory effects of moxifloxacin, cefuroxime, and vancomycin on human retinal vascular cells, human retinal vascular endothelial cells (RVEC) and pericytes were exposed to three antibiotics, and the adverse effects were assessed by membrane damage, loss of intrinsic esterase activity, kinetic cell viability, and inflammatory cytokine secretion. Their retinal toxicity was examined by live/dead assays after an intravitreal injection of the three antibiotics into mice eyes. In vascular cells in culture, membrane damage and loss of esterase activity were induced after exposure to the three antibiotics. The toxic effects were most obvious after moxifloxacin (RVEC, ≥125 μg/mL; pericytes, ≥1000 μg/mL) at 24 h. Cefuroxime also reduced esterase activity and the membrane integrity of vascular cells but were less toxic than moxifloxacin. Kinetic cell viability testing showed that 500 μg/mL of moxifloxacin exposure induced significant decrease (29%) in the viability as early as 1 h. When the inflammatory effects of the antibiotics were examined, a significant induction of IL-8 was observed especially by RVECs after exposure to cefuroxime or vancomycin which was exacerbated by L-alanyl-γ-D-glutamyl-meso-diaminopimelic acid (Tri-DAP), a NOD1 ligand. Intravitreal injections in mice showed that cefuroxime and vancomycin caused retinal and vascular toxicity extending to the inner nuclear layers. Collectively, moxifloxacin causes immediate damage to retinal vascular cells in vitro, while cefuroxime and vancomycin induced significant inflammatory effects on vascular endothelial cells and caused retinal toxicity. Surgeons need to be cautious of the toxicity when antibiotics are used prophylactically especially by intravitreal administration.

Intracameral antibiotics for prophylaxis of postoperative endophthalmitis in Australia: a review.

Postoperative endophthalmitis is a severe complication which may result in loss of vision. Intracameral antibiotics have been shown to reduce the risk of this complication and are extensively used worldwide, with vancomycin, cefuroxime and moxifloxacin most commonly used. Choices in Australia are currently limited to vancomycin and cefazolin, since cefuroxime and moxifloxacin are not available. Vancomycin has been safely and effectively used in our department for more than two decades. Recent publications have risen concerns regarding the association of haemorrhagic occlusive retinal vasculitis a potentially blinding complication with intracameral vancomycin. This concern has driven us to review the safety and efficacy of currently available antibiotics in the context of Australian practice.

Postoperative Hemorrhagic Occlusive Retinal Vasculitis Associated with Intravitreal Injection of Vancomycin

PURPOSE: To present a case of hemorrhagic occlusive retinal vasculitis (HORV) associated with intravitreal injection of vancomycin after pars plana vitrectomy (PPV).METHODS: Single case report.RESULTS: A 67-year-old woman presented with best corrected visual acuity (BCVA) of 20/400 in left eye. For clinical suspicion of chronic endophthalmitis, empirical treatment was initiated with vancomycin and ceftazidime without clinical improvement. The patient was submitted to pars plana vitrectomy. During surgery rhegmatogenous retinal detachment was observed and treated. At the end of surgery, intravitreal vancomycin was injected. After 18 days BCVA was counting fingers and fundus examination showed diffuse retinal vascular sheathing, intraretinal hemorrhages and ischemic macular whitening. The clinical diagnosis was compatible with HORV secondary to retinal toxicity due to intraocular vancomycin.CONCLUSIONS: This case illustrates the importance of including intravitreal vancomycin during PPV surgery on the list of potential causes when investigating a case of suspected hemorrhagic occlusive retinal vasculitis.

Hemorrhagic occlusive retinal vasculitis leading to the diagnosis of ciliary body melanoma

Hemorrhagic occlusive retinal vasculitis (HORV) is a condition associated with intraocular vancomycin during surgical intervention, most frequently following bilateral sequential cataract surgery. Because of the high rate of ophthalmic vascular complications in this condition, gonioscopic evaluation for identification of neovascularization of the angle and iris is essential. Careful examination can reveal previously asymptomatic and unassociated lesions of the iris or ciliary body. We present the case of a 71-year-old female who was diagnosed with a ciliary body melanoma secondary to complete ophthalmic examination associated with HORV. She reported decreased vision to light perception in the left eye (OS) following sequential, bilateral cataract surgery. Fundus examination OS demonstrated diffuse retinal vasculitis, retinal ischemia, and extensive hemorrhage. Evaluation included inflammatory and coagulopathy laboratory evaluation, carotid ultrasonography and magnetic resonance imaging (MRI) of the brain and orbits, all of which proved unrevealing, except for an enhancing mass OS on MRI. Further evaluation revealed a pigmented mass with features of melanoma in the anterior chamber angle extending into the ciliary body. Fine needle aspiration biopsy revealed high risk cytogenetic characteristics, and plaque radiotherapy was successfully employed.

Intracameral antibiotics during cataract surgery: evidence and barriers.

There is continuing debate regarding the safety, efficacy, and necessity of intracameral antibiotics to prevent postoperative endophthalmitis. We summarize the most recent evidence-based publications that either support or caution against this practice. Several additional large, international retrospective clinical studies found a significant reduction in endophthalmitis rates with intracameral antibiotic prophylaxis. Many surgeons are looking for alternatives to vancomycin for intracameral prophylaxis because of its association with the rare but sight-threatening complication of hemorrhagic occlusive retinal vasculitis. Although most efficacy data has been reported for intracameral cefuroxime, one of the largest clinical studies to date shows convincing efficacy with intracameral moxifloxacin prophylaxis. This same study reported a significant benefit with intracameral moxifloxacin following posterior capsular rupture, and surgeons should consider intracameral prophylaxis in these high risk cases. Despite mounting evidence that routine prophylaxis with intracameral cefuroxime and moxifloxacin reduce the endophthalmitis rate following cataract surgery, many surgeons have not adopted this practice. Reasons include lack of level 1 evidence from randomized trials, and the potential risks from compounding or mixing antibiotic solutions when no approved formulations are commercially available. Countries with commercially approved intraocular antibiotic formulations have the highest adoption rates of routine intracameral prophylaxis.

Early anti-VEGF treatment for hemorrhagic occlusive retinal vasculitis as a complication of cataract surgery

BackgroundWe report a case of hemorrhagic occlusive retinal vasculitis (HORV) after prophylactic intracameral vancomycin use during an uneventful cataract surgery treated with early anti-VEGF treatment.Case presentationA 51-year-old female underwent uneventful cataract surgery with prophylactic intracameral vancomycin during the procedure. On the seventh post-operative-day, she presented with sudden painful, visual loss. Fundus examination revealed peripheral hemorrhagic retinal vasculitis. She received anti-VEGF therapy to prevent further vision loss and retinal neovascularization due to extensive retinal ischemia. At the 6-month follow-up visit, visual acuity was 20/20 with no sign of neovascularization.ConclusionsPostoperative HORV is a devastating condition that can occur after otherwise uncomplicated cataract surgery. The nature of this rare condition remains unknown. Early anti-VEGF administration seems to demonstrate favorable results.

Endophthalmitis Reduction with Intracameral Moxifloxacin Prophylaxis: Analysis of 600 000 Surgeries

To compare the postoperative endophthalmitis rate before and after initiation of intracameral (IC) moxifloxacin prophylaxis for both phacoemulsification and sutureless, manual small-incision cataract surgery (M-SICS), as well as in patients with posterior capsular rupture (PCR). Retrospective, clinical registry. All cataract surgeries (617 453) performed during the 29-month period from January 2014 to May 2016 at the 10 regional Aravind eye hospitals were included. The electronic health record data for all study eyes were analyzed. Endophthalmitis rates before and after moxifloxaxin were statistically compared for all eyes and separately for both phacoemulsification and M-SICS, and for the eyes complicated by PCR. The postoperative endophthalmitis rates before and after initiation of IC moxifloxacin prophylaxis. Overall, 302 815 eyes did not receive IC moxifloxacin and 314 638 eyes did, and there was a significant decline in the endophthalmitis rate, from 0.07% (214/302 815) to 0.02% (64/314 638) (P < 0.001), with moxifloxacin. For the 194 252 phacoemulsification eyes, the endophthalmitis rate was 0.07% (75/104 894) without IC moxifloxacin prophylaxis, compared with 0.01% (11/89 358) with moxifloxacin (P < 0.001). For the 414 657 M-SICS eyes, the endophthalmitis rate was 0.07% (135/192 149) without IC moxifloxacin prophylaxis, compared with 0.02% (52/222 508) with moxifloxacin (P < 0.001). Approximately half of the 8479 eyes that had PCR received IC moxifloxacin, and half did not. Without IC moxifloxacin, PCR increased the endophthalmitis rate nearly 7-fold to 0.48% (20/4186); IC moxifloxacin reduced the endophthalmitis rate with PCR to 0.21% (9/4293) (P= 0.034). No adverse events were due to IC moxifloxacin. Routine IC moxifloxacin prophylaxis reduced the overall endophthalmitis rate by 3.5-fold (3-fold for M-SICS and nearly 6-fold for phacoemulsification). There was also a statistical benefit for eyes complicated by PCR, and IC antibiotic prophylaxis should be strongly considered for this high-risk population. These conclusions are strengthened by the high volume of cases analyzed at a single hospital network over a comparatively short time frame. Considering the association of hemorrhagic occlusive retinal vasculitis with vancomycin and the commercial unavailability of IC cefuroxime in many countries, moxifloxacin appears to be an effective option for surgeons electing IC antibiotic prophylaxis.

Vancomycin-Associated Hemorrhagic Occlusive Retinal Vasculitis: Clinical Characteristics of 36 Eyes

To expand understanding of presentation, diagnosis, and outcomes of hemorrhagic occlusive retinal vasculitis (HORV). Retrospective case series. Thirty-six eyes of 23 patients. The American Society of Cataract and Refractive Surgery (ASCRS) and the American Society of Retina Specialists (ASRS) formed a joint task force to define clinical characteristics of HORV and to study its prevalence, cause, treatment, and outcomes. An online registry was established on both societies' web sites. Surveys were e-mailed to members of both societies soliciting cases of suspected HORV. A literature search was performed to uncover additional cases. Historical data including intraoperative characteristics, images, treatment regimens, and visual and anatomic outcomes. Characteristic findings of HORV included unremarkable postoperative day 1 undilated examination, delayed-onset painless vision loss, mild anterior chamber and vitreous inflammation, sectoral retinal hemorrhages in areas of ischemia, and predilection for venules and peripheral involvement. Based on predetermined diagnostic criteria, 36 eyes of 23 patients were diagnosed with HORV. All eyes received intraocular vancomycin via intracameral bolus (33/36), via intravitreal injection (1/36), or through the irrigation bottle (2/36). Patients sought treatment with HORV 1 to 21 days after surgery or intravitreal injection. Visual results usually were poor: 22 of 36 eyes (61%) had 20/200 or worse visual acuity and 8 of 36 eyes (22%) had no light perception (NLP). Neovascular glaucoma developed in 20 of 36 eyes (56%). Seven eyes received additional intravitreal vancomycin after surgery; 5 of these 7 eyes had NLP visual acuity at the most recent examination. Three eyes received intravitreal corticosteroids and had final visual acuities of 20/40, 20/70, and hand movements. Hemorrhagic occlusive retinal vasculitis is a rare, potentially devastating condition that can develop after cataract surgery or intraocular injection. All cases in this series were associated with intraocular vancomycin. Disease course and findings suggest that HORV is caused by a delayed hypersensitivity reaction to vancomycin. Early treatment with corticosteroids likely is beneficial. Subsequently, anti-vascular endothelial growth factor injections and panretinal photocoagulation are important to prevent neovascular glaucoma, a common complication. Avoidance of additional intravitreal vancomycin is recommended if HORV is suspected.

Antibiotic prophylaxis in cataract surgery - An evidence-based approach.

Various protocols are being followed for endophthalmitis prophylaxis in cataract surgery, and this subject continues to be a matter of debate. We summarize the most recent evidence-based studies on this topic with additional stress on intracameral (IC) antibiotic prophylaxis. Here, we discuss several large, international clinical studies which discuss the efficacy, adoption, safety, cost, and newer trends in antibiotic prophylaxis. Majority of these studies report a significant reduction in endophthalmitis rates with IC antibiotic prophylaxis. Efficacy data have been reported for IC cefuroxime, vancomycin, and moxifloxacin. Surgeons are now looking for alternatives to vancomycin for IC prophylaxis because of its association with the rare but sight-threatening complication of hemorrhagic occlusive retinal vasculitis. A recent large clinical study shows convincing efficacy with IC moxifloxacin prophylaxis. Two large studies have also reported significant endophthalmitis reduction following use of IC antibiotic prophylaxis, in eyes with posterior capsule tear which are at highest risk for infection. Except for one randomized controlled trial, there is a lack of prospective data on this subject; however, considering the complexity of performing such studies, surgeons have to rely on the mounting evidence from other recent big data studies. Availability of approved intraocular antibiotic formulations will see a much higher adoption in the future.

The best of the best: a review of select retina case reports published in 2015

This review article highlights 4 case reports published in 2015 that provided substantive contributions to the field of retina. The first describes postoperative hemorrhagic occlusive retinal vasculitis, a newly described and visually devastating complication of cataract surgery. The second discusses ocriplasmin as a novel treatment for foveal schisis in patients with X-linked retinoschisis. The third describes a case of retinal toxicity from sertraline, a common psychiatric drug often sold as name brand Zoloft (Pfizer Inc, New York, NY). The last article shares 10-year results from a blind patient who received the Argus I retinal prosthesis. The study of vitreoretinal disease is both complex and fascinating. Case reports and case series are a means by which clinicians can share clinical experiences in managing retinal disease. By sharing our clinical experiences from individual patients, we begin the process of describing new diseases, new medications, and new surgical techniques. To obtain a list of published reports, we performed a MEDLINE search for case reports with the keyword retina. In 2015 there were 195 publications meeting these criteria. We selected 4 articles that highlight interesting developments in the field of retina.