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Published in final edited form as: Rev Neurol Dis. 2011 ; 8(1-2): 19.

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Hypertension-related eye abnormalities and the risk of stroke

Amanda D. Henderson, M.D.(1), Beau B. Bruce, M.D., M.S.(1),(2), Nancy J. Newman, MD(1),(2), and Valrie Biousse, MD(1),(2) (1)Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia
(3),
(2)Department (3)Department

of Neurology, Emory University School of Medicine, Atlanta, Georgia of Neurological Surgery, Emory University School of Medicine, Atlanta, Georgia

Abstract
Many studies have shown that hypertensive ocular funduscopic abnormalities are clearly related to stroke, even after controlling for level of blood pressure and other vascular risk factors. Retinal abnormalities indicative of a breakdown of the blood-retina barrier confer a greater increase in risk for stroke than sclerotic retinal changes. Similar retinal changes also have a positive relationship with stroke mortality. Hypertensive ocular fundus abnormalities are also reported to be associated with an increased risk for cognitive impairment, cerebral atrophy, progression of MRI-defined white matter lesions, and subclinical infarction. Recent advances in fundus photography allow for improved accuracy and consistency in interpretation of funduscopic lesions, and improve the feasibility of screening for these abnormalities in at-risk patient populations. Evaluating the ocular fundus for signs of hypertensive retinopathy, in combination with an assessment of the presence or absence of other known vascular risk factors, may allow clinicians to further individualize a risk profile for stroke to each individual patient, thus permitting more accurate risk stratification and, potentially, guiding treatment strategies.

Introduction
Hypertension causes microvascular damage in both the cerebral and retinal circulations (1 3). Because the retinal and cerebral vessels share embryological and anatomical characteristics, they also may show similar patterns of damage from diseases such as hypertension (3). Thus, it has long been suggested that examination of the ocular fundus could provide a noninvasive view of intracranial vascular pathology (2). Large populationbased studies have confirmed that standardized assessment of ocular fundus photographs provides reliable evaluation of retinal hypertensive abnormalities that have been correlated with a higher risk of cerebrovascular disease (Tables 1 and 2) (2,46). The retinal vessel pathology serves as an important marker for stratification of patients risk for having or developing cerebrovascular disease (2,46). Incorporation of these markers into risk stratification algorithms should enhance the ability to ensure appropriate clinical follow-up and treatment plans for each individual patient. To evaluate the potential value of retinal imaging as a tool to predict stroke risk, we describe the ocular effect of hypertension and review the reported associations between the ocular effects of hypertension and cerebrovascular disease.

Address correspondence to Dr. Valrie Biousse, Neuro-Ophthalmology Unit, Emory Eye Center, 1365-B Clifton Rd. NE, Atlanta, GA 30322. Phone: (404)778-5360. Fax: (404)778-4849. vbiouss@emory.edu. None of the authors have any conflict of interest.

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Ocular effects of systemic hypertension

Hypertension causes both acute and chronic ocular abnormalities. These changes affect different areas of the eye, producing three categories of hypertensive ocular change: choroidopathy, retinopathy, and optic neuropathy (Figures 1,2,3) (1,710).

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Hypertensive choroidopathy occurs as a result of choroidal ischemia, which develops because the choroidal vasculature does not possess the autoregulatory capacity of the retinal vasculature (1,710). Hypertensive choroidopathy can be divided into three phases. During the acute ischemic phase, choroidal arterioles constrict, leading to necrosis of the choriocapillaris and retinal pigment epithelium and the accumulation of exudates in the subretinal space. The clinical fundus findings during this phase include white areas (a manifestation of retinal pigment epithelium necrosis), and focal serous retinal detachment most often involving the macula and peripapillary region. Retinal fluorescein angiography shows patches of hypoperfused choriocapillaris, particularly in the central region of the macula. The chronic occlusive phase is characterized by extreme narrowing or occlusion of the choroidal capillaries and yellowing and leakage of the retinal pigment epithelium overlying the occluded regions. Retinal detachment also may occur in this phase. Degenerative retinal pigment epithelium lesions develop in the macula and peripheral retina and gradually become more extensive. Finally, during the chronic reparative phase of hypertensive choroidopathy, the occluded choroidal arteries, arterioles, and choriocapillaris are recanalized, the retinal pigment epithelium heals, and the retina reattaches. Chronic Elschnig spots, appearing as hyperpigmented areas with surrounding atrophy, or nonspecific areas of mottling, often remain. During this phase, fluorescein angiography shows underlying choroidal fluorescence (Figure 1). Hypertensive retinopathy describes a spectrum of microvascular abnormalities in people with elevated blood pressure and may be divided into several phases, which do not necessarily occur in the order described (1,710). In the vasoconstrictive phase, an acute rise in blood pressure causes the retinal vessels to increase their vascular tone, which manifests clinically as generalized retinal arteriolar narrowing. Alternatively, in vessels with significant arteriosclerosis, which prevents certain vascular segments from narrowing, more focal arteriolar narrowing occurs. The sclerotic phase of hypertensive retinopathy occurs in the presence of chronically elevated blood pressure and is characterized by hyperplasia of the tunica media, hyaline degeneration of the arteriolar wall, and intimal thickening, which manifest clinically as vessel attenuation, increased arteriolar light reflex, arteriovenous nicking, and increased tortuosity of arterioles. Arteriovenous nicking describes narrowing of a venule as an arteriole crosses over it. Increased arteriolar light reflex refers to an increased light reflex from the central portion of the retinal arteriolar surface (Figures 1 and 2). Sclerotic changes may lead to long-term complications, including macroaneurysms, microaneurysms, central retinal artery or vein occlusion, epiretinal membrane formation, cystoid macular edema, and vascular remodeling. Severely elevated BP may lead to the exudative phase, causing endothelial damage and disruption of the blood-retina barrier, with leakage of plasma and blood products into the vessel wall. This causes vessel dilation and eventual failure of autoregulation (Figure 3). The effects of this phase lead to many of the classic retinal signs associated with hypertensive retinopathy, including flame-shaped hemorrhages in the nerve fiber layer of the retina, dot and blot hemorrhages, boat-shaped hemorrhages, microaneurysms, hard exudates from the leakage of lipids, and cotton wool spots that represent infarctions of the nerve fiber layer (Figure 2). The most widely used scale for grading hypertensive retinopathy is the Keith, Wagener, and Barker classification, which grades retinopathy from I to IV based on its severity (Table 3) (11).

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Hypertensive optic neuropathy results from severely elevated blood pressure, and can also be divided into three phases (Figure 3) (1,710). During the acute ischemic phase, vasoconstriction in the prelaminar optic nerve leads to axonal hydropic swelling, axolemma disruption, and glial swelling. Vasoconstriction is more severe in the retrolaminar region and leads to endothelial swelling, degeneration of pericytes, and, eventually, vacuolated axons and glial swelling. This pathologic process occurs secondary to optic nerve ischemia, although raised intracranial pressure is also posited to play a role. Axonal swelling in the prelaminar optic nerve is decreased during the resolution phase. In the retrolaminar optic nerve, disintegrated myelinated axons and lipid-laden microglial cells are present. Degeneration of endothelial cells and pericytes is evident. In the atrophic phase, axons of the prelaminar optic nerve are replaced by proliferated glial cells, and myelinated axons largely disappear from the retrolaminar optic nerve. Additionally, lipid-laden microglia are absent at this stage. Some blood vessels lose their endothelial cells and pericytes and only retain a basement membrane. Clinically, chronic optic nerve swelling is progressively replaced by optic atrophy (Figure 3).

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Evaluating the ocular effects of hypertension with retinal photography

To evaluate hypertensive funduscopic damage, the retinal vasculature must be visualized either via funduscopy or photography. With the advent of digital fundus cameras, highresolution digital images are easily acquired and quality assessed instantly. Computerassisted image analysis techniques can be used to make quantitative measurements and to characterize abnormalities of the retinal microvasculature (12,13). Several studies show that the use of fundus photography results in more accurate documentation of the signs of retinopathy in the general population, when compared with clinical ophthalmoscopy (14 17). Depending on the camera used, fundus photography may require pharmacologic pupillary dilation or not. Non-mydriatic photography is advantageous because it avoids pupillary dilation, and is therefore less time consuming. However, dilated fundus photography may produce higher quality photographs in some patients. When evaluating non-mydriatic fundus photography for the Atherosclerosis Risk in Communities (ARIC) study, 81% of fundus photographs were deemed adequate for a retinal examination (18). Our group recently reported similar findings, with 83% of patients who had bilateral nonmydriatic fundus photography having a high quality photograph in at least one eye, and only 3% of patients having no photographs of diagnostic value (19). The percentage of patients with a quality dilated fundus photograph in at least one eye ranged from 92% to 98% in the Blue Mountains Eye Study (BMES), depending on the specific fundus abnormality being evaluated (20). The use of fundus photography for the acquisition of retinal images is a valuable tool for the evaluation of hypertensive ocular changes in patients at risk for cerebrovascular disease (14).

Ocular effects of systemic hypertension and stroke

Diverse study types provide evidence for the association between ocular fundus changes and cerebrovascular disease. Histologic studies showed that fibrous or fibro-hyalinoid thickenings of the retinal arteries near the optic disc reflect intracerebral arterial abnormalities, and are associated with an increased risk of both cerebral hemorrhage and cerebral infarction (3). Functional studies of the retinal vasculature show that prolonged retinal arteriovenous passage time is associated with lacunar infarction, confirmed by CT scan (21). Additionally, lower central retinal artery end-diastolic and mean velocities and higher central retinal artery resistive indices and pulsatility have been associated with cerebral small vessel disease (22).

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The strongest evidence supporting the use of hypertensive funduscopic findings in the stratification of patients at risk for cerebrovascular disease comes from longitudinal studies that evaluated the relationships between these ocular findings and cerebrovascular disease (Table 2). The initial studies examining these relationships, published in Japan during the 1970s through 1990s, reported associations between hypertensive funduscopic findings and subclinical and clinical stroke. However, many of these studies did not control for blood pressure, which may have influenced the results (2). More recent large population-based studies (Table 1), using photographs to define retinopathy signs, have provided further support for some of the earlier findings that, hypertensive ocular abnormalities predict stroke risk, even after controlling for blood pressure and other vascular risk factors (Table 2). In the ARIC study, hypertensive retinopathy increased the risk of stroke two- to three-fold (23). The BMES demonstrated a higher risk of combined stroke events (defined as incident stroke, transient ischemic attack or cerebrovascular death), in patients with hypertensive retinopathy (20). Significant, although generally weaker, relationships between other microvascular funduscopic findings and stroke have also been reported in the ARIC study (15,18), the Cardiovascular Health Study (CHS) (16,24,25), and the Rotterdam Eye Study (17,26,27). Arteriovenous nicking, focal arteriolar narrowing, microaneurysms, soft exudates, blot hemorrhages, flame-shaped hemorrhages, decreased arteriovenous ratio, and larger retinal venular caliber have been shown to be associated with increased risk for stroke (4,2331). In addition to subclinical and clinical stroke, stroke mortality may be related to retinal hypertensive abnormalities. The BMES and BDES reported a relationship between retinopathy and cerebrovascular death in patients without diabetes. However, these studies did not detect any relationship between retinal arteriolar diameter or focal arteriolar narrowing and cerebrovascular death (4,20,28,32). Several studies have focused on the relationship between hypertensive retinopathy and abnormalities detected on brain imaging. Retinopathy, arteriovenous nicking, retinal arteriolar sclerosis, and focal arteriolar narrowing have been associated with cerebral white matter lesions, even after controlling for blood pressure (3235). Interestingly, in the Rotterdam Eye Study, retinal vessel diameter was not related to the severity of cerebral small vessel disease; however, larger retinal venular diameter was associated with marked progression of periventricular white matter lesions and subcortical white matter lesions over time, after adjusting for vascular risk factors (27). These findings are consistent with the idea that retinal microvasculature abnormalities likely precede and are harbingers of the development of cerebral white matter lesions. Not only are cerebral white matter lesions related to retinal hypertensive abnormalities, but they are also related to stroke. The presence of MRI-defined white matter lesions has been shown to be associated with an increased risk of incident clinical stroke, and, importantly, the presence of both retinopathy and cerebral white matter lesions has shown a multiplicative effect on the risk for clinical stroke (33,34). This interaction between retinopathy and white matter lesions may have two possible explanations: microvascular pathology may be more severe in patients with both retinopathy and white matter lesions, or retinopathy may be a marker for a more malignant form of cerebral white matter lesions. Regardless of the reason, this relationship suggests that funduscopic examination or retinal photography is useful for risk stratification in patients with evidence of cerebral white matter lesions on MRI (34).

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Conclusion and future perspectives

The presence of hypertensive funduscopic abnormalities is clearly related to stroke, even after controlling for level of blood pressure and other vascular risk factors. Retinal changes

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indicative of a breakdown of the blood-retina barrier (such as retinal hemorrhages, microaneurysms and cotton wool spots) seem to confer a greater increase in stroke risk than sclerotic retinal changes (such as generalized and focal retinal arteriolar narrowing and arteriovenous nicking). Evaluating for these retinal signs, along with the assessment of the presence or absence of other known vascular risk factors, may allow clinicians to further individualize a risk profile for stroke for each patient. This would permit more accurate risk stratification and, potentially, play a role in guiding treatment strategies. With continuing improvement in retinal photographic techniques and retinal image analysis, evaluation of retinal microvascular signs of hypertension from retinal photographs may begin to move from predominately the research arena to clinical practice. The use of nonmydriatic fundus photography, in particular, allows for easy screening for funduscopic abnormalities in the neurologists office.

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Acknowledgments
This study was supported in part by a departmental grant (Department of Ophthalmology) from Research to Prevent Blindness, Inc., core grant P30-EY06360 (Department of Ophthalmology), KL2- RR025009 (BBB), UL1RR025008 (BBB/VB), K23-EY019341 (BBB), and the Knights Templar Eye Foundation (BBB/VB). Dr. Bruce received the American Academy of Neurology Practice Research Fellowship. Dr. Newman is a recipient of the Research to Prevent Blindness Lew R. Wasserman Merit Award.

References
Only very few relevant articles to this review were selected in the list below (there are hundreds of excellent articles relating to this topic).
1. Wong TY, Mitchell P. The eye in hypertension. Lancet. 2007; 369:425435. [PubMed: 17276782] 2. Wong TY, Klein R, Klein BE, et al. Retinal microvascular abnormalities and their relationship with hypertension, cardiovascular disease, and mortality. Surv Ophthalmol. 2001; 46:5980. [PubMed: 11525792] 3. Goto I, Katsuki S, Ikui H, et al. Pathological studies on the intracerebral and retinal arteries in cerebrovascular and noncerebrovascular diseases. Stroke. 1975; 6:263269. [PubMed: 50653] 4. Baker ML, Hand PJ, Wang JJ, Wong TY. Retinal signs and stroke: revisiting the link between the eye and brain. Stroke. 2008; 39:13711379. [PubMed: 18309171] 5. Wong TY, McIntosh R. Systemic associations of retinal microvascular signs: a review of recent population-based studies. Ophthalmic Physiol Opt. 2005; 3:195204. [PubMed: 15854064] 6. Wong TY, McIntosh R. Hypertensive retinopathy signs as risk indicators of cardiovascular morbidity and mortality. Br Med Bull. 2005; 73 and 74:5770. [PubMed: 16148191] 7. Tso MO, Jampol LM. Pathophysiology of hypertensive retinopathy. Ophthalmology. 1982; 89:11321145. [PubMed: 7155524] 8. Hayreh SS, Servais GE, Virdi PS, et al. Fundus lesions in malignant hypertension. III. Arterial blood pressure, biochemical, and fundus changes. Ophthalmology. 1986; 93:4559. [PubMed: 3951816] 9. Hayreh SS, Servais GE, Virdi PS. Fundus lesions in malignant hypertension. VI. Hypertensive choroidopathy. Ophthalmology. 1986; 93:13831411. [PubMed: 3808599] 10. Hammond S, Wells JR, Marcus DM, et al. Ophthalmoscopic findings in malignant hypertension. Journal of clinical hypertension (Greenwich, Conn). 2006; 8:221223. 11. Keith N, Wagener H, Barker NW. Some different types of essential hypertension: their course and prognosis. Am J Med Sci. 1939; 196:223229. 12. Liew G, Wang JJ, Mitchell P, Wong TY. Retinal vascular imaging: a new tool in microvascular disease research. Circ Cardiovasc Imaging. 2008; 2:156161. [PubMed: 19808533] 13. Patton N, Aslam T, Macgillivray T, et al. Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures. J Anat. 2005; 206:319348. [PubMed: 15817102]

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14. Wong TY. Is retinal photography useful in the measurement of stroke risk? Lancet Neurol. 2004; 3:17983. [PubMed: 15029894] 15. The ARIC investigators. The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. Am J Epidemiol. 1989; 129:687702. [PubMed: 2646917] 16. Fried LP, Borhani NO, Enright P, et al. The Cardiovascular Health Study: design and rationale. Ann Epidemiol. 1991; 1:263276. [PubMed: 1669507] 17. Hofman A, Breteler MM, van Duijn CM, et al. The Rotterdam Study: 2010 objectives and design update. Eur J Epidemiol. 2009; 24:553572. [PubMed: 19728115] 18. Hubbard LD, Brothers RJ, King WN, et al. Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the Atherosclerosis Risk in Communities Study. Ophthalmology. 1999; 106:22692280. [PubMed: 10599656] 19. Bruce BB, Lamirel C, Wright DW, et al. Non-mydriatic ocular fundus photography reveals unrecognized relevant findings in the ED: the FOTO-ED study. NEJM. 2011; 364:387389. [PubMed: 21268749] 20. Mitchell P, Wang JJ, Wong TY, et al. Retinal microvascular signs and risk of stroke and stroke mortality. Neurology. 2005; 65:10051009. [PubMed: 16217050] 21. Schneider R, Rademacher M, Wolf S. Lacunar infarcts and white matter attenuation. Ophthalmologic and microcirculatory aspects of the pathophysiology. Stroke. 1993; 24:1874 1879. [PubMed: 8248970] 22. Hiroki M, Miyashita K, Yoshida H, et al. Central retinal artery Doppler flow parameters reflect the severity of cerebral small-vessel disease. Stroke. 2003; 34:e9294. [PubMed: 12775884] 23. Wong TY, Klein R, Couper DJ, et al. Retinal microvascular abnormalities and incident stroke: the Atherosclerosis Risk in Communities Study. Lancet. 2001; 358:11341140. [PubMed: 11597667] 24. Longstreth W Jr, Larsen EK, Klein R, et al. Associations between findings on cranial magnetic resonance imaging and retinal photography in the elderly: the Cardiovascular Health Study. Am J Epidemiol. 2007; 165:7884. [PubMed: 17041135] 25. Wong TY, Kamineni A, Klein R, et al. Quantitative retinal venular caliber and risk of cardiovascular disease in older persons: the cardiovascular health study. Arch Intern Med. 2006; 166:23882394. [PubMed: 17130394] 26. Ikram MK, de Jong FJ, Bos MJ, et al. Retinal vessel diameters and risk of stroke: the Rotterdam Study. Neurology. 2006; 66:13391343. [PubMed: 16682664] 27. Ikram MK, De Jong FJ, Van Dijk EJ, et al. Retinal vessel diameters and cerebral small vessel disease: the Rotterdam Scan Study. Brain. 2006; 129:182188. [PubMed: 16317022] 28. Wong TY, Klein R, Nieto FJ, et al. Retinal microvascular abnormalities and 10-year cardiovascular mortality: a population-based case-control study. Ophthalmology. 2003; 110:933 940. [PubMed: 12750093] 29. Witt N, Wong TY, Hughes AD, et al. Abnormalities of retinal microvascular structure and risk of mortality from ischemic heart disease and stroke. Hypertension. 2006; 47:975981. [PubMed: 16585415] 30. Hirai FE, Moss SE, Knudtson MD, et al. Retinopathy and survival in a population without diabetes: The Beaver Dam Eye Study. Am J Epidemiol. 2007; 166:724730. [PubMed: 17591594] 31. Wang JJ, Liew G, Klein R, et al. Retinal vessel diameter and cardiovascular mortality: pooled data analysis from two older populations. Eur Heart J. 2007; 28:19841992. [PubMed: 17626032] 32. Kwa VI, van der Sande JJ, Stam J, et al. Retinal arterial changes correlate with cerebral smallvessel disease. Neurology. 2002; 59:15361540. [PubMed: 12451193] 33. Kobayashi S, Okada K, Koide H, et al. Subcortical silent brain infarction as a risk factor for clinical stroke. Stroke. 1997; 28:19321939. [PubMed: 9341698] 34. Wong TY, Klein R, Sharrett AR, et al. Cerebral white matter lesions, retinopathy, and incident clinical stroke. Jama. 2002; 288:6774. [PubMed: 12090864] 35. Kwon HM, Kim BJ, Oh JY, et al. Retinopathy as an indicator of silent brain infarction in asymptomatic hypertensive subjects. J Neurol Sci. 2007; 252:159162. [PubMed: 17182058]

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Main points The presence of hypertensive funduscopic abnormalities is clearly related to stroke, even after controlling for level of blood pressure and other vascular risk factors. Retinal changes indicative of a breakdown of the blood-retina barrier (such as retinal hemorrhages, microaneurysms and cotton wool spots) seem to confer a greater increase in stroke risk than sclerotic retinal changes (such as generalized and focal retinal arteriolar narrowing and arteriovenous nicking). With continuing improvement in retinal photographic techniques and automated retinal image analysis, evaluation of retinal microvascular signs of hypertension from retinal photographs may begin to move from predominately the research arena to clinical practice. Evaluation for signs of hypertensive retinopathy, along with the assessment of the presence or absence of other known vascular risk factors, may allow clinicians to further individualize a risk profile for stroke for each patient, thus permitting more accurate risk stratification and, potentially, guiding treatment strategies.

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Figure 1.

Evolution of severe bilateral hypertensive retinopathy and choroidopathy over time (the right eye is on the left and the left eye is on the right). Top row of photographs: Acutely, the patient complains of mild bilateral visual loss and blood pressure is 224/68 mmHg. Note the attenuation of retinal arteries, dilation of the veins, cotton wool spots (soft exudates) (white circle), flame shaped hemorrhages (white arrowheads), hard exudates (white arrow), and Elschnig spots (star). There is macular edema bilaterally, which explains the decreased visual acuity. Second row of photographs: Retinal fluorescein angiography showing hyperfluorescence at the level of the Elschnig spots (star), and microaneurysms (white arrows). Third row of photographs: Retinal appearance two weeks later (after normalization of blood pressure). Note the improvement of macular edema and the increased hard exudates.

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Bottom row of photographs: Three months later, the cotton wool spots and retinal hemorrhages have resolved. The arterial attenuation persists, and the veins are less dilated. Both optic nerves have become slightly pale.

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Figure 2.

Stage III/IV hypertensive retinopathy (the right eye is on the left and the left eye is on the right). There is mild bilateral optic nerve edema. Note the arteriovenous nicking (white arrows), the flame hemorrhage (white arrowhead), the boat-shaped hemorrhage (star), and the arteriolar narrowing (black arrows).

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Figure 3.

Severe stage IV hypertensive retinopathy with bilateral optic nerve head edema in the setting of malignant hypertension (the right eye is on the left and the left eye is on the right). Top row of photographs: Acutely, there is severe bilateral optic nerve head edema with dilated and tortuous veins and exudates. Bottom row of photographs: Three months after treatment of hypertension, the optic nerve edema has resolved, but the patient has developed severe bilateral optic nerve atrophy.

Table 1

Recent large population-based studies evaluating the relationships between ocular effects of hypertension and cerebrovascular disease

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Study name or

Number of

Age range in years

Cardiovascular Health Study (CHS) 5888 6597

Prospective cohort study based on sampling from Medicare eligibility lists, non- institutionalized, ambulatory men and women age 65 and older were enrolled, including 5201 at 4 US field centers (Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Allegheny County, Pennsylvania) in 198990, and an additional 687 African-American participants in 199293 at 3 of the 4 sites.

Atherosclerosis Risk in Communities (ARIC) study 15,792 4564

Population samples were selected by probability sampling methods in 19871989 from 4 US communities: Forsyth County, North Carolina (n = 4,035); Jackson, Mississippi (blacks only; n = 3,728); the northwestern suburbs of Minneapolis, Minnesota (n = 4,009); and Washington County, Maryland (n = 4,020).

Beaver Dam Eye Study (BDES) 3654 14,926 >45 4997

4926

4384

A private census of the population of Beaver Dam, Wisconsin (US) was performed from September 15, 1987 to May 4, 1988 to identify all residents in the city or township of Beaver Dam, Wisconsin, who were 43 to 84 years of age. Of the 5924 eligible individuals, 4926 participated in the baseline examination between March 1, 1988 and September 14, 1990. 3684 of those surviving (81.1%) participated in the 5-year follow- up examination between March 1, 1993 and June 14, 1995. Population-based survey of vision and eye disease in an urban population aged 49 years or older, resident in two postcode areas in the Blue Mountains region, west of Sydney, Australia. Prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort.

Blue Mountains Eye Study (BMES)

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Rotterdam Eye Study

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Table 2

Association of hypertensive retinal microvascular changes and neurologic and cardiovascular complications in recent large population-based studies
Retinal microvascular changes Retinal hemorrhages Microaneurysms Cotton wool spots Associations Current blood pressure Carotid artery disease Incident clinical stroke Subclinical cerebral disease (MRI) Cognitive impairment Cardiovascular mortality Renal dysfunction Arterio-venous nicking Current blood pressure Past blood pressure Incident clinical stroke Subclinical cerebral disease (MRI) Renal dysfunction Metabolic syndrome Focal arteriolar narrowing Current blood pressure Incident hypertension Metabolic syndrome Generalized arteriolar narrowing Current blood pressure Past blood pressure Incident hypertension Incident clinical stroke Carotid atherosclerosis Incident heart disease Cardiovascular mortality Metabolic syndrome Larger retinal venular caliber Incident clinical stroke Cardiovascular mortality Associations Stroke Ischemic heart disease Grade III hypertensive retinopathy Stroke Cognitive impairment Cardiovascular mortality Renal dysfunction Grade IV hypertensive retinopathy Mortality Strength of association* +++ +++ +++ +++ +++ +++ +++ +++ +++ ++ ++ + + +++ +

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+++ +++ ++ + ++ ++ + + ++

Severity of hypertensive retinopathy (See Table 3) Grade I/II hypertensive retinopathy

Strength of association* +/++ +/++ +++ +++ +++ +++ +++

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Strength of association: +++ (relative risk/odds ratio >2.0); ++ (relative risk/odds ratio 1.52.0); + (relative risk/odds ratio <1.5)

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Table 3

Keith, Wagener, and Barker classification of hypertensive retinopathy, which grades retinopathy from I to IV based on its severity (11)
Grade I Grade II Grade III Grade IV Slight or modest narrowing of the retinal arterioles, with an arteriovenous ratio of 1:2 Modest to severe narrowing of retinal arterioles with an arteriovenous ratio <1:2 or arteriovenous nicking Soft exudates or flame-shaped hemorrhages Bilateral optic nerve edema

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