We are all busy clinicians, and each of us has practices that vary in treatment modalities and focus of care. But for just about all of us, eventually, or regularly for that matter, retinal vein occlusions will present to the office. How they are managed will vary widely from office to office, but for those patients presenting with a retinal vein occlusion without macular edema, the clinical evaluation, management and workup of the patient falls within the wheelhouse of optometry. As these patients do not need surgical intervention, they do need a medical evaluation, in which the OD plays an integral role.
What is the incidence of retinal vein occlusion? Branch retinal vein occlusion (BRVO) is more commonly seen than central retinal vein occlusions (CRVO). It’s estimated that the prevalence and 15-year cumulative incidence of BRVO is about 2% and for CRVO about 0.2%(1). It affects over 17 million people worldwide each year (2). RVOs are roughly equally distributed between men and women, with a slight leaning toward increased in incidence amongst women (2).
Retinal vein occlusions can present as a central retinal vein occlusion, or a branch or hemispheric retinal vein occlusion. Patients with retinal vein occlusions do report decreased quality of life and burden due to the disease (1) which is proportional to the level of visual impairment. Therefore it is imperative that a targeted systemic workup of these patients be performed early so as to identify the underlying etiology and address it so as to mitigate the long-term effects and reduction in vision and quality of life.
Central retinal vein occlusions occur due to thrombus formation in the central retinal vein, posterior to the visible aspects of the optic nerve head, usually at the level of the lamina cribrosa or more posteriorly. Branch retinal vein occlusions occur due to impedance of blood flow through a distal retinal vein, and hemispheric retinal vein occlusions occur due to blockage of one of two branches of the central retinal vein in the optic nerve head. But at the end of the day, all vein occlusions are due to blockage in the venous drainage system of the anterior retinal circulation. While the arteriolar portion of the anterior retinal vascular system can sometimes play a role in the onset of the disease process of vein occlusion, retinal vein occlusions are NOT due to embolic phenomenon, which is restricted to the arterial system.
So what exactly is a thrombus? Thrombosis occurs when blood clots form in arteries or veins. Thrombi that move from one location to another are considered thromboemboli, and these usually occur in the arterial system or larger veins of the body. A good example of an arterial thromboemboli is a clot that forms in the heart secondary to blood flow disruption in patients with A-fib that becomes dislodged and can end up in the retinal arterial circulation. An example of a venular thromboembolus is the development of a pulmonary embolus, which begins as a venular clot often in the popliteal vein behind the knee that becomes dislodged and moves into progressively larger veins and ultimately the inferior vena cava, passes through the right side of the heart, and become lodged in a pulmonary artery….while it ends in an artery, it began in a vein. The terms thrombus and blood clot are often used interchangeably.
What causes a clot, or the preferred term, thrombus, to form? This is where differences begin to occur, between arterial and venous thrombi. In both cases, one of the easiest ways to create a thrombus is to do two things: reduce blood flow, and /or make blood flow turbulent. Arterial thrombi often form as a result of atherosclerosis. Atherosclerosis is a progressive inflammatory vasculopathy affecting small, medium, and larger arteries, often associated with hyperlipidemia, hypertension, and diabetes, though other risk factors such as smoking play a role in its development. As the arterial lumen gradually diminishes, blood flow adjacent to the vessel wall begins to become turbulent and sluggish, setting the stage for a thrombus to form. Essentially it is a clotting problem brought on by disrupting the arterial flow. This is the basis of atherosclerosis…fatty deposits in the intimal lining of arterioles, along with calcium accumulation, brought on by vessel inflammation, lead to plaque formation in the arterial walls. This plaque then disrupts blood flow, which in turn precipitates a clot (thrombus) in the vessel lumen, distal to the plaque.
In venous thrombosis, the role of atherosclerosis plays a secondary role in the development of the thrombus. While atherosclerosis may result in distal end organ decreased blood flow, that decreased blood flow in the arterial system subsequently results in decreased blood flow in the venular system. Slowing the blood flow down sets the stage for a thrombus to form. Patients who develop pulmonary thromboses often times do so because they are bedridden for extended periods of time (low flow in the veins in the legs because of limited movement) or because they sat on a plane for a long flight without moving their legs (low flow in the veins in the leg); the net result is the same….low blood flow through veins is a risk factor for clots.
So what in the world does the aforementioned discussion of arterial and venular thrombosis have to do with retinal vein occlusions? Remember, retinal vein occlusions are due to clots forming in a retinal vein. Those clots can occur behind the lamina, at the lamina, or in the distal retinal venular circulation.
We have a distinct advantage as eye specialists in facilitating the determination of the underlying cause of retinal vein occlusion. While the effects of retinal vein occlusion can be clinically obvious, close scrutiny of the retinal arterioles plays a critical role in determining the etiology. So why look at the retinal arteries? The answer: because they can give us a big clue as to the underlying condition(s) that may be playing a role in the development of the VO.
How does that help us, you may ask? Well, let’s take a look at the risk factors for the development of RVOs. Aside from age (the older you are the higher the likelihood of developing RVO), the main systemic risk factors for developing RVOs are elevated cholesterol, elevated blood pressure, and diabetes. Interestingly, these are the SAME risk factors for the development of atherosclerosis. When examining the retina, look carefully for arteriolarsclerosis of the retinal arterioles. That is important for a simple, physical reason: retinal arteries are hard-walled, whereas retinal veins are soft-walled, and are prone to compression from overlying sclerotic retinal arteries. Retinal arterioles that have evidence of atherosclerosis can, understandably, compress the underlying retinal vein, and disturb blood flow through that vein. Mind you, the overlying atherosclerotic arteriole does not need to fully compress the underlying vein; it only needs to do so to the extent that it disturbs flow….slows flow if you will….enough to precipitate thrombus formation. In other words, if we see a retinal vein occlusion, the first place you need to look is at the arteries. If there is evidence of atherosclerosis, then perhaps one or more of the risk factors for atherosclerosis may be out of line, therein helping you to highlight what to evaluate as the true cause of the vein occlusion. You know there is a thrombus there, but what caused the thrombus? Elevated cholesterol? Elevated blood pressure? Diabetes? Smoking? Obesity?
Just because your patient is already on medication for elevated cholesterol does not mean their lipids are all well in order. Perhaps their total cholesterol is adequate, but their LDL levels are too high. Perhaps their ratio of subtype LDL particles is skewed such that the total LDL level is fine, but the proportion of LDL particles is such that the patient has worsening atherosclerosis in spite of therapy. Just because they are a medicated diabetic, perhaps their glucose control is not at the level it needs to be. Perhaps their blood pressure needs to be lower. By examining the retinal arterioles and seeing atherosclerosis, you now have some information germane to the patient’s internist, and can give them something to consider being more aggressive about treating.
So needless to say, tight lipid, glucose, and blood pressure are part and parcel of controlling the risk factors that can precipitate worsening atherosclerosis, which in turn can precipitate a vein occlusion. But what if your patient is younger, ‘healthy’ with no signs of atherosclerosis…what then?
Well, that goes back to what causes a vein occlusion….a thrombus…a clot. What can make a seemingly healthy young patient clot? Two things: antiphospholipid antibody syndrome and Factor V Leiden! Antiphospholipid antibody syndrome is an autoimmune condition whereby the patient produces cardiolipin antibodies which increase coagulability. The condition causes thrombi in both the arterial and venular systems. Classically these patients often have a history of multiple miscarriages. Factor V Leiden, on the other hand, is a genetic condition that is transmitted in an autosomal dominant fashion. This condition also increases coagulability, and most commonly causes thrombi in the venular system.
There are other risk factors for the development of RVOs other than those listed above, one of which is IOP. Elevated IOP can induce vein occlusions by….guess what….the same mechanism….impeding retinal venular blood flow out of the eye. If we lower IOP, and the vein occlusion begins to clear, didn’t we just ‘fix’ the vein occlusion?
Certainly, if there is macular edema present, the patient would benefit from anti-VEGF treatment, which means heading to the retinologist. But what if there is no macular edema? Quite simply, it’s an internal medicine issue that is managed by the OD and the internist. This is a nonsurgical retina…. which means it’s owned by optometry. You’ve got this!
REFERENCES:
1. The burden of disease of retinal vein occlusion: review of the literature M Laouri,1,* E Chen,1 M Looman,1 and M Gallagher2 Eye (Lond) v.25(8); 2011 Aug PMC3178209
2. Global epidemiology of retinal vein occlusion: a systematic review and meta-analysis of prevalence, incidence, and risk factors Peige Song,1 Yuehong Xu,2 Mingming Zha,2 Yan Zhang,3 and Igor Rudan1 J Glob Health. 2019 Jun; 9(1): 010427.
