Glaucoma suspect presents with bilateral peripapillary cotton wool spots
A 54-year-old man presented for a routine clinic visit at the New England Eye Center, Tufts Medical Center, where he is followed annually as a glaucoma suspect. He was feeling subjectively stable without any ocular complaints.
The patient was followed annually as a low-risk glaucoma suspect based on large cup-to-disc ratio in both eyes with historically normal glaucoma testing. His medical history was significant for type 2 diabetes, hypertension and hyperlipidemia, and his daily medications include metformin, metoprolol and atorvastatin. He had no known drug allergies.
Examination
On examination in May 2022, visual acuity was 20/25 in the right eye and 20/30 in the left eye. IOP was 13 mm Hg in both eyes. The pupils were round and briskly reactive to light with no afferent pupillary defect. Ocular motility was full and orthophoric, and visual fields were normal by confrontation. There was 1+ nuclear sclerosis in both eyes, but otherwise the anterior segment exam was within normal limit.
The posterior segment exam showed pink and healthy optic nerves with large discs, large cups and intact neuroretinal rim that appeared stable compared to prior exams. Notably, there were multiple white fluffy retinal lesions that appeared to be in the superficial retina, consistent with cotton wool spots (CWS), in a peripapillary distribution worse in the right eye than in the left eye. Additionally, a flame-shaped retinal hemorrhage superior to the right optic nerve was noted, as well as fine telangiectatic vessels temporal to the right optic nerve (Figure 1).
Source: Omar Abu-Qamar, MD, Jarod Santoro, MD, Maggie Wei, MD, Caroline Baumal, MD, and Sarwat Salim, MD
Further imaging
Macular OCT through the white retinal lesion showed focal inner retinal thickening and hyperreflectivity within the nerve fiber layer, consistent with CWS (Figure 2). Similar findings were noted on OCT of the left eye.
OCT of the retinal nerve fiber layer (RNFL) showed increased average thickness of the RNFL bilaterally with values of 140 µm and 122 µm in the right eye and left eye, respectively (Figure 3). Guided progression analysis confirmed that this increase in thickness was statically significant compared with the patient’s 2016 baseline.
The 24-2 Humphrey visual field (HVF) of the right eye was a fairly reliable test that showed nonspecific central deficits. The 24-2 HVF of the left eye was unreliable due to high fixation losses with nonspecific deficits (Figure 4).
Fluorescein angiography (FA) showed possible delayed filling and blockage and/or capillary nonperfusion in regions corresponding to the CWS. There was trace late leakage and patchy fine telangiectatic vessels around the CWS in later frames (Figure 5). FA of the left eye showed similar findings.
What is your diagnosis?
See answer below.
Cotton wool spots
The exam and imaging findings of bilateral cotton wool spots in a peripapillary distribution with normal-appearing optic nerves are consistent with Purtscher retinopathy or, in the absence of a history of trauma, pseudo-Purtscher retinopathy. Such findings necessitated a more thorough history taking and review of systems, which revealed recent changes in the patient’s medical history.
While he denied any history of compressive injury to the head or chest, he reported presenting to Tufts Medical Center about 1 month prior with non-exertional chest pain and was found to have a non-ST-elevation myocardial infarction. Therefore, he underwent coronary catheterization, which revealed multivessel disease and subsequently underwent open-heart surgery with coronary artery bypass grafting (CABG) of four vessels. Per chart review, the patient had poor adherence to medications before his admission, and his blood pressure on admission was elevated (systolic approximately 180 mm Hg and diastolic approximately 100 mm Hg). His recent HbA1c level was 8.2%. His basic lab workup, including complete blood count (CBC) and comprehensive metabolic panel (CMP), was unremarkable.
Differential diagnosis
The differential diagnosis for this patient’s presentation is wide and includes hypertensive retinopathy, diabetic retinopathy (DR), infectious etiologies (namely HIV), Purtscher or pseudo-Purtscher retinopathy, collagen vascular disease (such as lupus, granulomatosis with polyangiitis), radiation retinopathy, cancer (metastasis, leukemia) and hypercoagulable state (polycythemia vera, multiple myeloma).
The differential diagnosis can be narrowed by excluding hypertensive retinopathy given the absence of other hallmark features such as lack of arteriovenous nicking, disc edema or copper wiring. The same applies to DR, which is unlikely given the absence of microaneurysms, venous beading and microvascular abnormalities, among other DR features. Other diagnoses can be excluded by negative history and normal workup (testing for CBC, CMP and HIV was negative). Given the characteristic exam findings and distribution of the retinal lesions, Purtscher retinopathy was high on the differential. In the absence of trauma, the diagnosis was presumed to be pseudo-Purtscher retinopathy.
Discussion
Purtscher retinopathy was first described by Othmar Purtscher in 1912 when he reported a series of patients with decreased vision and characteristic retinal lesions in a peripapillary distribution after head trauma. The condition was later named after him and expanded to include retinopathy after compressive trauma of the head, chest or long bones. The constellation of retinal lesions in Purtscher includes CWS, Purtscher flecken and retinal hemorrhages, with or without optic disc swelling. The pathophysiology of Purtscher is not completely understood but thought to be complement-mediated leukoembolization of the precapillary arteriolar system, and it remains uncertain why the embolization occurs in a peripapillary distribution. Our patient demonstrated CWS (present in 93% of patients), white fluffy lesions that obscure the retinal vessels and result from occlusion of the superficial radial peripapillary capillaries. When the deeper capillaries are occluded, Purtscher-flecken lesions (present in 63% of patients) are seen and appear as intraretinal whitening with a clear zone between the lesion and the vessels.
Purtscher, by definition, is in the setting of trauma; however, similar findings can be found in nontraumatic conditions, in which case it is described as Purtscher-like or pseudo-Purtscher retinopathy. The two conditions are presumed to share similar pathophysiology, but the constitution of the emboli in pseudo-Purtscher varies depending on the underlying condition. Multiple conditions were reported with pseudo-Purtscher and include acute pancreatitis, fat embolic syndrome, chronic renal failure, amniotic fluid embolization, autoimmune diseases (lupus, Sjögren’s syndrome), retrobulbar anesthesia and orbital steroid injection.
Review of systems and lab workup done during this patient’s recent hospitalization were not suggestive of the pseudo-Purtscher conditions listed above, and this raised the question as to whether there could be an association between CABG and pseudo-Purtscher. Tzu and colleagues reported a case of a 60-year-old man who presented with painless visual field loss 10 days after CABG and was found to have unilateral pseudo-Purtscher retinopathy that improved with observation. Several other papers have described embolic retinal phenomena following major cardiothoracic surgeries that involved the use of the cardiopulmonary bypass (CBP) machinery used in CABG. It was hypothesized that the CBP machinery results in platelet damage, which then aggregates and causes short-lived infarcts in multiple organs, including the retina. Kusano and colleagues reported bilateral CWS in a peripapillary distribution in seven patients who underwent coronary intervention, suggesting that retinal infarcts can be seen even after less invasive cardiac interventions such as coronary catheterization.
Although the level of evidence for an association between retinal embolic events and cardiac interventions is limited to cases series and does not establish causation, there is sufficient evidence to at least suggest an association. The fact that most of these embolic events are not vision threatening and improve with observation alone suggests that such events are probably underreported. Interestingly, in a prospective observational study of 20 subjects who underwent transcatheter aortic valve implantation, the rate of retinal embolic events was as high as 15% and the rate of new retinal abnormalities was 20%.
The management of our patient’s pseudo-Purtscher retinopathy, presumed to be secondary to CABG, involves treating the underlying condition with a goal of preventing further ischemia and embolic events. Our patient previously underwent extensive cardiac testing, including carotid Doppler ultrasound, during his hospitalization, and his blood pressure and glucose levels were under better control since his hospital discharge. He continues to follow closely with his PCP and cardiologist, and we plan to follow up with the patient in 1 month for a repeated dilated fundus exam.
- References:
- BCSC. Retina. Section 13. American Academy of Ophthalmology. 2020-2021;171-173.
- Fusi-Rubiano WJ, et al. BMJ Open Ophthalmol. 2017;doi:10.1136/bmjophth-2016-000033.
- Kusano Y, et al. Am J Ophthalmol. 2003;doi:10.1016/s0002-9394(03)00267-8.
- Liang MC, et al. Man referred for sudden onset decline in vision in left eye. https://www.healio.com/news/ophthalmology/20150516/j241_3310_32_news_print_1. Published May 18, 2015.
- Maassen J, et al. Purtscher’s retinopathy: 22-year-old male with vision loss after trauma. https://eyerounds.org/cases/39-PurtschersRetinopathyAngiopathiaRetinaTraumatica.htm. Published May 18, 2005.
- Marren SE. Optom Vis Sci. 1994;doi:10.1097/00006324-199407000-00006.
- Purtscher O. Graefes Arch Ophthalmol. 1912;82:347-371.
- Trethowan BA, et al. J Cardiothorac Surg. 2011;doi:10.1186/1749-8090-6-154.
- Witkin AJ, et al. Bilateral areas of retinal whitening and cotton wool spots seen in young man. https://www.healio.com/news/ophthalmology/20131026/10_3928_1081_597x_20130101_01_1315908. Published Oct. 1, 2013.
- For more information:
- Omar Abu-Qamar, MD, Jarod Santoro, MD, Maggie Wei, MD, Caroline Baumal, MD, and Sarwat Salim, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.
- Edited by Allison V. Coombs, DO, MS, and Nisha S. Dhawlikar, MD, MPH. They can be reached at New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.