Abstract
Introduction: This case report highlights the importance of knowing what nonprescription medications and supplements are being taken by patients in addition to their prescribed medications. Case Presentation: A 48-year-old myopic male presented with a 1-day history of hand motion vision. He was found to have an extensive vitreous hemorrhage with no view of the fundus. On follow-up 4 days later, he continued to have a significant vitreous hemorrhage and a B scan that showed a possible retinal tear. Upon having surgery 7 days later, he was found to have a temporal retinal detachment with subretinal fluid and hemorrhage extending to, but not involving, the macula. His postoperative course was complicated by persistent preretinal and subretinal hemorrhages along with recurrent retinal detachments requiring 2 additional surgeries. He was evaluated by his primary care physician and had a normal thrombotic work-up and all his dietary supplements, including turmeric, were discontinued. At post-op month 2, he continued to improve with resolving subretinal hemorrhage and an attached retina. Conclusion: This case report describes the extensive and recurrent subretinal hemorrhage that can develop in those patients taking medications or supplements with anticoagulant and/or antiplatelet properties. These antithrombotic agents are not only limited to prescription medications but can also include dietary supplements such as turmeric. It highlights the importance of knowing both the medications and dietary supplements a patient uses as this can affect the long-term outcome.
Introduction
Rhegmatogenous retinal detachment (RRD) is the most common type of retinal detachment, affecting 1 in 10,000 people per year [1]. A RRD involves a retinal tear or hole which allows fluid from the vitreous cavity to enter the subretinal space, resulting in a separation between the neurosensory retina and the retinal pigment epithelium (RPE). Direct contact between the neurosensory retina and the RPE is essential to maintain a normal functioning retina and preserve vision. If this contact is interrupted for too long, retinal ischemia will develop resulting in loss of retinal function. The known risk factors for a RRD include pathologic myopia, lattice degeneration, trauma, previous intraocular surgery, peripheral retina changes such as enclosed ora bays, previous retinal detachment in the fellow eye, and family history [2, 3]. The most common cause of a RRD is a posterior vitreous detachment (PVD) [2]. A PVD is a natural and normal phenomenon that involves the vitreous separating from the retina. If the contraction of the vitreous gel occurs over the attachment to a blood vessel, this can result in a vitreous or subretinal hemorrhage. A PVD can also lead to a retinal tear and/or detachment.
Subretinal hemorrhages can occur at the time of development of a RRD and can complicate the surgical repair of a RRD. This blood, which is located between the neurosensory retina and the RPE, can originate from either the retinal or choroidal vasculature. There are multiple risk factors for the development of a subretinal hemorrhage which may include trauma, hypertension, and the use of anticoagulants [4]. Anticoagulants can include medications specifically prescribed for this purpose but also supplements that have this property among many others. Turmeric, also known as curcumin, is one such supplement.
Case Report
A 48-year-old myopic male presents with a 1-day history of right eye blurry vision. He denied flashes/floaters prior to noticing the blurry vision. He also denied taking any blood thinning medication. On initial presentation to the ophthalmology office, his vision was hand motion right eye, 20/20 left eye. His pupils were symmetric with no afferent pupillary defect. The intraocular pressure was 12 in the right eye and 15 in the left eye. The extraocular movements were full and the confrontation of visual fields was full on the left but unable to see in the right eye. The anterior segment slit lamp exam was unremarkable. The dilated fundus examination showed vitreous hemorrhage right eye with no view to the fundus while the left eye was unremarkable. The differential at this time was a hemorrhagic PVD, valsava retinopathy as he was at the gym earlier that day before noticing the blurry vision, or RRD with vitreous hemorrhage. Four days later, the vision was unchanged as was the rest of the exam. At this time, he was diagnosed with a hemorrhagic PVD with an area suspicious for a small retinal tear on ultrasound. He was given the option of surgery versus observation and elected to defer surgery. At follow-up 5 days later, the ultrasound showed evidence of a retinal detachment and the decision was made to proceed with surgery. Two days later, he had a 25-gauge pars plana vitrectomy (PPV) (DORC EVA vitrectomy system)/perfluorocarbon/air-fluid exchange/endolaser photocoagulation/instillation of 20% SF6 gas right eye. He was found to have a temporal retinal detachment with subretinal fluid extending to, but not involving, the macula. There was also subretinal hemorrhage present. There were two horseshoe tears superiorly and additional subretinal hemorrhage at 9 o’clock with an adjacent retinal hole but no bridging vessels were noted in the area. On postoperative day (POD) 1, he was noted to have an inferotemporal subretinal clot (shown in Fig. 1), but the retina was attached and VA stable at hand motion. This subretinal clot remained stable at postoperative day 3 but by postoperative day 7, there was some temporal preretinal hemorrhage. During repeat examination on postoperative day 10, there was increased subretinal fluid and vitreous hemorrhage completely limiting the view of the fundus with a possible inferotemporal retinal detachment. The decision was made to observe but 10 days later, the vitreous hemorrhage persisted, and the subretinal fluid had worsened, so a repeat 23g PPV/perfluoro-n-octane/retinotomy/air-fluid exchange/endolaser/silicone oil was done. During the surgery, he was noted to have a total 360-degree retinal detachment with extensive subretinal hemorrhage. At postoperative day 1, there was continued subretinal and preretinal hemorrhage with an inferotemporal clot and by postoperative week 2, there was an inferior retinal detachment with subretinal fluid extending to the inferior macula but sparing the fovea. Three days later, he had a repeat PPV/pars plana lensectomy and now also had a scleral buckle placed. At postoperative week 2, the retina remained attached and the subretinal hemorrhage was resolving. Given his recurrent subretinal hemorrhages, he was referred to his primary care doctor for a coagulation work-up. He had a normal complete blood count and coagulation work-up and also stopped his turmeric supplement which he had been taking for approximately 3 months. At postoperative month 2, he continued to improve with resolving hemorrhage.
1) Inferotemporal clot surrounded by laser. 2) Inferonasal subretinal fluid.
Discussion
RRD repair can be a complicated situation and the postoperative course may not always be straightforward. In our case, the postoperative course was complicated by unanticipated recurrent subretinal hemorrhages in conjunction with recurrent retinal detachments. In such a presentation, an investigation is warranted to determine if a patient has a pathologic reason for the recurrent hemorrhage or is using a blood thinning medication. Many pharmaceutical medications are used specifically as antithrombotics, including anticoagulants like warfarin and direct-acting oral anticoagulants, and antiplatelet drugs such as clopidogrel and aspirin. However, there are many supplements that also can mimic these anticoagulant or antiplatelet effects and this may not be known to the patient or the physician.
Turmeric is an herb derived from the roots of the plant, Curcuma longa, and is largely used in India and Southern Asia [5]. Curcumin is the main active ingredient in turmeric. It is used while cooking but is also taken as an herbal supplement for various indications. There is increasing research being done on turmeric which has shown that curcumin can modulate multitarget signal transduction [6]. As a result of this signaling pathway activation, it has anti-inflammatory, antioxidant, antineoplastic, and antiplatelet properties among others, and can theoretically be used to treat many different diseases. Some of these potential diseases include Alzheimer disease, diabetes, hyperlipidemia, viral infections, dermatologic diseases, and cardiovascular diseases [5, 7‒9].
In addition to the above properties, curcumin has well known antiplatelet activity. The primary function of platelets is to quickly aggregate at the site of vascular injury to curtail bleeding. However, platelets also combine with neutrophils, monocytes, and other types of cells in various inflammatory and thrombotic states. They are involved in the pathogenesis of various inflammatory diseases such as psoriasis and atopic dermatitis. Platelet aggregation can play a significant role in the pathogenesis of many cardiovascular diseases and as a result, antiplatelet therapy is suggested to treat and/or prevent a range of cardiovascular diseases such as myocardial infarctions, ischemic cerebrovascular accidents, and vascular stent placements. Patients may turn to turmeric for this effect and use it alone or in conjunction with a prescribed medication.
However, there are downsides to using herbal medications. In addition to not knowing the exact properties of an herbal supplement, the appropriate therapeutic doses have not been clearly studied and the supplement market is not regulated by the Food and Drug Administration. Turmeric is known to have poor bioavailability as well as low chemical stability [6] which can make accurate dosing difficult and lead to amplified effects of the medication. Also, patients do not view herbal supplements as medications and thus are less likely to disclose use to a treating physician which may result in complications such as those experienced by our patient.
This case report is limited because it cannot be proven that the turmeric supplement was the direct cause of the recurrent retinal hemorrhage and detachment. However, it is hypothesized that the turmeric use led to an increased risk of bleeding and once the turmeric supplement was stopped, the recurrent subretinal hemorrhages resolved and his retina remained attached.
Conclusion
Physicians should be aware that herbal supplements are not benign. While they often may have positive contributions to health, they can mimic the effects of many prescription medications which may lead to untoward outcomes such as excessive bleeding.
The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material at https://doi.org/10.1159/000545076.
Acknowledgments
The authors would like to thank Akrit Sodhi MD PhD, Fatemeh Rajaii MD PhD, and Fasika Woreta MD.
Statement of Ethics
Ethical approval is not required for this study in accordance with local or national guidelines. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images.
Conflict of Interest Statement
The following authors have no financial disclosures: Sherry Narang Kalla.
Funding Sources
This study was not supported by any sponsor or funder.
Author Contributions
S.N.K. wrote the paper in entirety.
Data Availability Statement
All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.