Ischemic retinal disorders: What to know and look for

Retinal vascular diseases represent a spectrum of vision-threatening conditions that are often closely linked to systemic vascular pathology. Ischemic retinal disorders can present with acute or progressive vision loss and may signal underlying cardiovascular risk. Understanding their clinical features, diagnostic approaches, and management strategies is critical, as timely recognition not only affects visual outcomes but may also identify patients at increased risk for stroke and other serious systemic outcomes.

Ocular ischemic syndrome

Ocular ischemic syndrome (OIS) is a rare, yet vision-threatening condition, characterized by hypoperfusion of the retinal arteries due to atherosclerosis.¹ This condition most commonly affects older adults, with the mean age of affliction at 65 years old, and is rare in patients prior to 50 years of age.¹ Men are affected by the condition twice as often as women, which is primarily due to the cardiovascular risk factors that affect males more often than females.¹ There is no racial predilection for the disorder.² Patients with OIS have a stenosis of 90% or more of the common or internal carotid artery on the same side that the syndrome is found, with 50% of the cases resulting in complete blockage of the artery.¹ Patients afflicted with OIS have a comorbidity of hypertension in 73% of cases and diabetes in 56%.¹ OIS typically presents with unilateral vision loss in 90% of patients. Of those patients, the vision loss is gradual over weeks to months in 67%.¹ Additionally, dull, gradual pain in the afflicted eye is present in 40% of patients, and this is typically due to neovascular glaucoma.^1,2 Although anterior segment signs may occur (such as rubeosis irides in 67% of patients leading to neovascular glaucoma), posterior signs are the most common.^1,3 In the midperiphery, retinal hemorrhages are seen in 80% of affected eyes, and microaneurysms can also be found.¹ Venous stasis retinopathy can also include signs of narrowed retinal arteries (90%) and dilated nontortuous retinal veins (90%).³ Retinal neovascularization can also occur, primarily in the optic disc.¹ Imaging of the carotid arteries is the diagnostic test for OIS.¹ Carotid duplex ultrasound can detect high degree (70%-99%) carotid stenosis in the neck with 89% sensitivity and 84% specificity.⁴ Fluorescein angiography (FA) can also be utilized to determine if OIS is present. Delayed choroidal filling is present, as well as prominent arterial staining and prolonged arteriovenous transit time.^2,5 Management of OIS consists of a multidisciplinary approach. Treatment of associated cardiovascular risk factors is necessary, which can include statin use, antiplatelet medications, and lifestyle modifications.³ Ocular management of OIS depends on the ocular adverse effects that are present. For example, high IOP must be evaluated and managed.³ For patients with posterior segment neovascularization, panretinal photocoagulation (PRP) is recommended.³ Additional treatment may include anti-VEGF agents such as bevacizumab to manage the neovascularization.⁵ Unfortunately, OIS does not produce a favorable outcome. The mortality rate of OIS is 40% within 5 years of onset, primarily due to cardiac issues.¹ Additionally, OIS is associated with a significantly higher rate of strokes, with an annual stroke rate of 4% compared with 0.49% in controls.⁴

Central retinal artery occlusion

Central retinal artery occlusion (CRAO) is a sight-threatening ocular emergency that leads to sudden, severe vision loss.⁶ This condition is a result of interrupted blood flow through the central retinal artery, due to vasospasm or thromboembolism. This leads to ischemia of the inner retinal layers, in particular, the ganglion cell and nerve fiber layers.⁶ The incidence ranges from 1 to 1.9 per 100,000 individuals in the US, with the risk of CRAO increasing with age.⁶ In 98% of cases, the condition is unilateral.⁶ CRAO can be placed into one of 2 categories: (1) Nonarteritic CRAO (90%) is primarily caused by embolism due to carotid atherosclerosis; or (2) Arteritic CRAO is caused by systemic inflammatory diseases, the most important being giant cell arteritis.⁶ CRAO typically presents as profound, painless vision loss.⁷ In 80% of eyes, vision is no better than counting fingers.⁷ There is also an ipsilateral relative afferent pupillary defect, as well as significant visual field changes.⁷ Typical clinical features of patients with CRAO include attenuated retinal arterioles, extensive retinal whitening (ischemia), and the presence of a cherry-red spot due to preservation of optic nerve perfusion.⁷ Additional features include multiple cotton wool spots or whitening around the fovea.⁸ Arterial emboli are present in 20% to 40% of patients.⁸ As in OIS, anterior segment neovascularization is common and can lead to neovascular glaucoma.⁷ Apart from the clinical picture, diagnostic tools include OCT, demonstrating increased macular thickness compared with the fellow eye. FA would demonstrate delayed arterial filling.⁸ Time is of the essence in attempting to treat CRAO, as infarction can occur in only 12 to 15 minutes after a complete CRAO.⁷ There are many conflicting theories on the best option of treatment in CRAO, and whether those treatments are even efficacious or simply not worthwhile. Intravenous thrombolysis has been studied: In a 2015 patient-level meta-analysis, Schrag and colleagues found that systemic thrombolysis was beneficial at 4.5 hours or earlier after vision loss compared with the natural history group, for vision loss from 20/200 to worse, to an improvement of 20/100 to better.^7,9 Intraarterial thrombolysis permits a high concentration of the lytic agent to be delivered to the clot.⁷ Nonthrombolytic therapies have been theorized to aid in CRAO therapy. These include vasodilation to increase retinal perfusion (via carbogen inhalation, pentoxifylline), dislodging the embolus via rapid fluctuation in IOP (ocular massage or laser embolysis), or increasing retinal arterial perfusion pressure (IOP-lowering therapies). However, none of these therapies has been shown to be effective in improving visual acuity or outcome.⁷ Patients diagnosed with CRAO need immediate referral to the emergency department or stroke presentation service.⁷

Central retinal vein occlusion

With a prevalence rate of 0.1% to 0.4% in patients aged 40 years or older, retinal vein occlusion is one of the most common retinal vascular diseases in the aging population, secondary only to diabetic retinopathy as a leading cause of vascular blindness.¹⁰ Central retinal vein occlusion (CRVO) affects male and female patients equally, and is most common in patients older than 65 years.¹¹ The Eye Disease Case-Control Study found an increased risk of CRVO in patients with diabetes and hypertension.¹¹ Although the pathophysiology of CRVO is poorly understood, histopathologic studies of eyes enucleated with CRVO found a thrombus occluding the lumen of the central retinal vein.¹¹ Locally, compression of the central retinal vein can occur by an atherosclerotic central retinal artery.¹¹ Patients younger than 60 years may present with hypercoagulable or inflammatory conditions.¹¹ Although typically unilateral, CRVO can affect the fellow eye at an annual risk of 1% to 3%.¹¹ CRVO typically presents as a sudden painless loss of vision, although the change may occur gradually.¹¹ In the Central Retinal Vein Occlusion Study (CVOS), 29% of patients presented with a visual acuity of 20/40 or better, 43% of patients presented with a VA of 20/50 to 20/200, and 28% of patients were initially 20/200 or worse.¹² Visual distortion can also be present.¹² The typical clinical picture in CRVO is intraretinal hemorrhages (postflame shaped and dot blot), as well as dilated, tortuous retinal vessels in all 4 quadrants.¹¹ The hemorrhages radiate from the optic nerve head, leading to the classic “blood and thunder” appearance.¹¹ Cotton-wool spots, cystoid macular edema (CME), and optic nerve head swelling may also be present in varying degrees.¹¹ Additionally, neovascularization of the optic disc and neovascularization elsewhere can develop due to retinal ischemia.11 Anterior segment changes include neovascularization of the iris or angle.¹¹ OCT, OCTA, and FA can determine the extent of CME, as well as macular or peripheral perfusion, which can affect vision.¹¹ The CVOS classified the perfusion status as perfused, nonperfused, or indeterminate based on FA: A perfused (nonischemic) CRVO demonstrates fewer than 10 disc areas of retinal capillary nonperfusion on FA, whereas a nonperfused (ischemic) CRVO demonstrates more than 10 disc areas of retinal capillary nonperfusion on FA.¹¹ This is important to note because perfused CRVO results in better initial and final visual acuity.¹¹ Blindness and visual morbidity in CRVO are primarily due to macular edema, macular ischemia, or neovascular glaucoma. Multiple treatments have been studied, such as anti-VEGF treatments for macular edema and neovascular glaucoma, as well as PRP.¹¹ Options that have been FDA approved for the treatment of CRVO include ranibizumab, aflibercept, and sustained-release dexamethasone implant.¹¹

Diagnostic workup

Diagnostic imaging workup for a patient with suspected carotid artery disease may include carotid duplex ultrasound, CT angiogram of the head and neck, and/or echocardiogram with bubble study to evaluate for the presence of patent foramen oval (PFO).¹³ If a PFO is identified, a Doppler ultrasound of the lower extremities may be considered to evaluate for deep venous thrombosis and possible embolic phenomenon.¹³ Laboratory workup may include coagulation studies with PT/INR/PTT, hemoglobin A1c, and lipid panel.¹³ Hypercoagulable workup is typically deferred to the outpatient setting and not performed in the setting of an acute thrombus, given the risk of false positives and confounding results. In the setting of an acute stroke or high-risk transient ischemic attack defined by an ABCD2 score of greater than 4, 81 mg of aspirin and 75 mg of clopidogrel daily for 21 days has been beneficial in weighing risk for bleeding, followed by monotherapy.¹³ Neurology and/or hematology consultations should also be considered.¹³

References

1. Terelak-Borys B, Skonieczna K, Grabska-Liberak I. Ocular ischemic syndrome - a systemic review. Med Sci Monit. 2012;18(8):RA138-144. doi:10.12659/msm883260

2. Ávila-Figueroa E, Flores-Calvo M, Sánchez-Rodríguez CC, et al. Ocular ischemic syndrome secondary to carotid-artery disease: a comprehensive review addressing critical early detection, management, and education. Front Ophthalmol (Lausanne). 2026;6:1717841. doi:10.3389/fopht.2026.1717841

3. Metry Y, Joseph S. Optic disc neovascularization as the only sign of ocular ischemic syndrome: a case report. Cureus. 2022;14(10):e29972. doi:10.7759/Cureus.29972

4. Ghoraba HH, Yu M, Yu G, et al. Ocular ischemic syndrome in the setting of normal carotid duplex ultrasound. Retin Cases Brief Rep. 2025;19(2):221-224. doi:10.1097/ICB.0000000000001528

5. Fortun JA. Ocular ischemic syndrome. Ophthalmology. 2023;507-510. Elsevier Inc.

6. Rizzo C, Mercuri S, Lavia C, et al. Ocular massage in central retinal artery occlusion: monitoring vascular recovery with optical coherence tomography analysis - a case series. Am J Ophthalmol Case Rep. 2025;41:102512. doi:10.1016/j.ajoc.2025.102512

7. Quinn MP. The current treatment of branch retinal artery occlusion and central retinal artery occlusion. Advan Ophthalmol Optom. 2024;9(1):p235-247. doi:10.1016/j.yaoo.2024.03.001

8. Chen SN, Chao CC, Hwang JF, Yang CM. Clinical manifestations of central retinal artery occlusion in eyes of proliferative diabetic retinopathy with previous vitrectomy and panretinal photocoagulation. Retina. 2014;34(9):1861-1866. doi:10.1097/IAE.0000000000000158

9. Schrag M, Youn TS, Schindler J, et al. Intravenous tibrinolytic therapy in central retinal artery occlusion: A patient-level meta-analysis. JAMA Neurology. 2015;72(10):1148-1154. doi:10.1001/jamaneurol.2015.1578

10. Shimura M, Yasuda K, Nakagawa T, Takeshita T, Shiono T, Sakamoto T. Combination therapy for retinal vein occlusion. Ophthalmology. 2010;117(9):p1858-1858.e3. https://www.aaojournal.org/article/S0161-6420(10)00396-9/fulltext

11. Oellers P. Central retinal vein occlusion. Ryan’s Retina. 2023;7:1189-1204.

12. Spaide RF. Fekrat S, ed. When do I refer a patient with a central retinal vein occlusion, what is the work-up, and what are the treatment options? Curbside Consultation in Retina: 49 Clinical Questions, Second Edition. CRC Press; 2018.

13. Johnston SC, Elm JJ, Easton JD, et al; for the POINT and Neurological Emergencies Treatment Trials Network Investigators. Time course for benefit and risk for clopidogrel and aspirin after acute transient ischemic attack and minor ischemic stroke: a secondary analysis from the POINT randomized trial. Circulation. 2019;140(8):658-664. doi:10.1161/CIRCULATIONAHA.119.040713