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Case Report
Ophthalmic artery ischemia in hemophagocytic lymphohistiocytosis: A case report and review of current literature
1 MBBS, Junior Doctor, Whittington Hospital, London, United Kingdom
2 MBBS, Junior Doctor, University College Hospital, London, United Kingdom
3 MD, Consultant Ophthalmic Surgeon and Vitreoretinal Surgeon, Ophthalmology Department, Royal Free Hospital, London, United Kingdom
4 PhD, Consultant Ophthalmic Surgeon and Neuro-ophthalmologist, National Hospital for Neurology & Neurosurgery, Neuro-ophthalmology Department, Queen Square, London, United Kingdom
5 BM, MD, Associate Professor and Consultant Ophthalmologist and Vitreoretinal Specialist, Ophthalmology Department, Royal Free Hospital, London, United Kingdom
Address correspondence to:
Ayushi Gupta
Whittington Hospital, Magdala Avenue, London N19 5NF,
United Kingdom
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Article ID: 100040Z17AG2024
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Gupta A, Shah N, ElHousseini Z, Bremner F, Asaria R. Ophthalmic artery ischemia in hemophagocytic lymphohistiocytosis: A case report and review of current literature. J Case Rep Images Opthalmol 2024;7(1):5– 13.ABSTRACT
Introduction: This case report describes the ocular manifestations of hemophagocytic lymphohistiocytosis in a 35-year-old male with suspected Adult-onset Still’s Disease. Documented ocular presentations of hemophagocytic lymphohistiocytosis are variable, and the pathophysiology remains unclear. A complete review of the current literature suggests that posterior segment findings, including retinal and vitreous hemorrhage, are most common.
Case Report: Here we describe the first published case of bilateral combined choroidal and retinal ischemia in a patient with ocular hemophagocytic lymphohistiocytosis. This is suggestive of complete ophthalmic artery occlusion driving proliferative retinopathy. Mechanistic hypotheses include anemia, thrombocytopenia, coagulopathy, and histiocytic infiltration.
Conclusion: In this case, pre-retinal hemorrhage, retinal hemorrhage, and vitreous hemorrhage were treated with panretinal photocoagulation, pars plana vitrectomy, and bevacizumab at different stages in each eye. Unusually for ocular hemophagocytic lymphohistiocytosis, the patient developed a unilateral tractional retinal detachment, later thought to be due to early administration bevacizumab prior to vitrectomy in the left eye. Final visual acuity in this patient remains poor, and worse in the left eye. We therefore suggest early vitrectomy to maintain adequate views of the fundus before bevacizumab or panretinal photocoagulation in this patient cohort.
Keywords: Choroidal ischemia, Ocular hemophagocytic lymphohistiocytosis, Ophthalmic artery occlusion, Retinal ischemia
Introduction
Hemophagocytic lymphohistiocytosis (HLH) is a rare immune disease, mediated by uncontrolled macrophage, natural killer cell and cytotoxic T-lymphocyte activation, and resulting in disseminated intravascular coagulation and multi-organ dysfunction [1],[2]. Hemophagocytic lymphohistiocytosis is classified into primary (genetic) or secondary (acquired or reactive), and the mortality rate is as high as 57.8% [2],[3]. Previously, ocular involvement was considered rare; however, the latest evidence suggests that as many as 39% of HLH patients have some degree of ocular sequelae [4]. Several case reports of HLH with various types of ocular involvement have been published to date, with one retrospective study performed. We report the first case of combined retinal and choroidal ischemia in ocular HLH.
Case Report
A previously healthy 35-year-old man developed arthralgia, fever, rash, and malaise. He presented to Accident and Emergency (A&E) with a seizure and reduced Glasgow Coma Scale (GCS), requiring intubation. During his hospital stay he was extensively investigated with blood tests, brain imaging, lumbar puncture, and liver, spleen, skin and bone marrow biopsies, and genetic testing (Table 1 and Table 2). Investigations were in-keeping with a diagnosis of secondary HLH (H score 217), with previously undiagnosed Adult-onset Still’s Disease thought to be the driver. He was transferred to a tertiary center for ongoing management with anakinra, high-dose intravenous (IV) methylprednisolone, and etoposide.
Once extubated, he reported bilateral visual symptoms including dry eye and reduced visual acuity (VA) at the level of counting fingers (CF). Bedside fundoscopy found severe bilateral four quadrant retinal hemorrhages and peripapillary cotton-wool spots. There was no uveitis and the optic discs were normal. Appearances were in-keeping with an ischemic retinal vasculopathy with differentials including intravascular lymphoma.
Following a 5-month hospital stay he was followed up in the Ophthalmology clinic where he was found to have bilateral macular ischemia, 4-quadrant preretinal and retinal hemorrhages (RH), and right vitreous hemorrhage (VH) (Figure 1A and Figure 1B). Fundus fluorescein angiography (FFA) demonstrated poor retinal and choroidal filling (Figure 2A and Figure 2B). Visual acuity at this time was hand movements (HM) in the right eye (RE) and 6/60 in the left eye (LE). He was managed with panretinal photocoagulation (PRP) in the RE as the view of the fundus was preserved, and VA temporarily improved to CF.
However, two months after presentation to the eye clinic, the VH worsened in his RE and a dense VH developed in his LE (Figure 3A and Figure 3B) reducing VA to CF RE and HM LE. He underwent right pars plana vitrectomy with EndoLaser and received bevacizumab bilaterally. Five months later, the patient developed a LE tractional retinal detachment (TRD) with VA worsened to no perception of light (NPL). He underwent left pars plana vitrectomy with EndoLaser retinopexy, but there was no recovery of sight. Following these interventions, his VA is now stable at CF RE and NPL LE.
Discussion
Currently, there are 19 case reports (Table 3), 3 case series (Table 4), and 1 retrospective study regarding ophthalmic manifestations of HLH [4]. Posterior segment findings are well documented in the literature. Retinal hemorrhages and VH are some of the most common manifestations of HLH, and these are in keeping with the fundus examination in our case [4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14] (Figure 1A, Figure 1B and Figure 3A, Figure 3B). However, our FFA images reveal reduced retinal filling and poor choroidal filling (Figure 2A and Figure 2B), not previously identified in the literature. These findings are suggestive of complete ophthalmic artery involvement.
Ischemia of the ophthalmic artery is thought to have driven proliferative retinopathy, resulting in RH and eventually VH in both eyes in our patient. The pathophysiology of ocular findings in HLH has been hypothesized to be due to lymphohistiocytic infiltration and inflammation, coagulopathy leading to ischemic vasculopathy, exacerbated by anemia [6],[7],[8],[9],[10],[12],[13],[15],[16],[17],[18],[19],[20],[21],[22]. These are all plausible hypotheses causing bilateral ophthalmic artery ischemia in our case.
Serous retinal detachment has been documented in ocular HLH and pathophysiology is in keeping with an inflammatory or infiltrative process [4],[19],[23]. However, the TRD seen in our patient is not explained by our ischemic hypothesis. Although commonly used as an adjunct to TRD repair in proliferative retinopathy, bevacizumab has been shown in some cases to result in development or progression of TRD [24],[25]. Therefore, it is possible that bevacizumab contributed to the LE TRD in our case.
Visual acuity outcomes are not always reported in the literature as many cases occur in children or patients are systemically very unwell (Table 3 and Table 4). However, reported VA is generally poor. In our case, outcomes were better in the RE, which received vitrectomy prior to treatment with bevacizumab. Therefore, we advocate for early vitrectomy in cases of ocular HLH with VH to enable visualization, assessment, and prompt treatment of retinal pathology with PRP or intravitreal bevacizumab.
Conclusion
Ocular manifestations of HLH are more common than previously believed. Emerging evidence suggests that the posterior segment is most commonly affected. To our knowledge, this is the first documented case of combined retinal and choroidal ischemia in a single individual with ocular HLH, suggestive of complete ophthalmic artery involvement in this patient. Visual acuity is often poor; however, early vitrectomy in cases of VH may improve longer term visual outcomes.
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SUPPORTING INFORMATION
Author Contributions
Ayushi Gupta - Conception of the work, Design of the work, Acquisition of data, Drafting the work, Final approval of the version to be published, Agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Neal Shah - Final approval of the version to be published, Agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Zine ElHousseini - Final approval of the version to be published, Agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Fion Bremner - Final approval of the version to be published, Agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Riaz Asaria - Final approval of the version to be published, Agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Guaranter of SubmissionThe corresponding author is the guarantor of submission.
Source of SupportNone
Consent StatementWritten informed consent was obtained from the patient for publication of this article.
Data AvailabilityAll relevant data are within the paper and its Supporting Information files.
Conflict of InterestAuthors declare no conflict of interest.
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