Microvascular Findings in Patients with Rheumatoid Arthritis - Assessed, Using Fundus Photography and Fluorescein Angiography

Hyun Jung Yeo; Ji Hyun Lee; Hong Jik Lee; Ki Sup Byun; Ho Joon Im; Min Jung Kim

doi:10.4078/jrd.2013.20.4.231

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Yeo, Lee, Lee, Byun, Im, and Kim: Microvascular Findings in Patients with Rheumatoid Arthritis - Assessed, Using Fundus Photography and Fluorescein Angiography

Original Article

J Rheum Dis 2013;20(4):231-237.

Published online: 31 August 2013

DOI: https://doi.org/10.4078/jrd.2013.20.4.231

Microvascular Findings in Patients with Rheumatoid Arthritis - Assessed, Using Fundus Photography and Fluorescein Angiography

Hyun Jung Yeo, Ji Hyun Lee, Hong Jik Lee, Ki Sup Byun, Ho Joon Im, Min Jung Kim

Division of Rheumatology, Department of Internal Medicine, Maryknoll Medical Center, Busan, Korea

Corresponding to : Ji Hyun Lee, Division of Rheumatology, Department of Internal Medicine, Maryknoll Medical Center, 12-9, Daechung-dong 4-ga, Jung-gu, Busan 600-730, Korea. E-mail : ete@lycos.co.kr

Received 12 March 201324 May 2013 Accepted 24 May 2013

This is a Free Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

Although a series of trials support that rheumatoid arthritis (RA) is associated with increased atherosclerosis, the link between microvascular structural changes and the disease activity of RA has not been clarified. We measured changes in the retinal micro-vasculature using fundus fluorescein angiography (FAG) and investigated the association between the retinal vasculature and clinical parameters of RA.

Methods

Seventy-five RA patients and sixty healthy control were included. Morphometric and quantitative features in the capillary images including retinal vascular signs and vessel diameters were measured with fundus photography and FAG. RA activity was assessed based on high sensitivity C-reactive protein (hsCRP), disease activity score with 28 joints (DAS 28), and health assessment questionnaire (HAQ).

Results

Central retinal arteriolar equivalents (CRAE) was 118.1±31.3 μm in RA patients and 123.8±19.9 μm in control subjects, showing the tendency of retinal arteriolar narrowing in patients with RA but without statistical significance. The mean central retinal venular equivalents (CRVE) was 162.4±26.4 μm which was significantly higher than that of control group (144.1±23.1 μm, p<0.001). The prevalence of AVN was 34.7%, and significantly higher in RA group. Among retinal findings, the presence of early pinpoint hyperfluorescence and areas of delayed choroidal perfusion correlated with hsCRP. Age, disease duration, DAS 28, HAQ, and rheumatoid factor (RF) had no effect on CRAE and CRVE. In multivariate analysis, only hsCRP was found to be associated with wider venular caliber.

Conclusion

Retinal venular widening was more common in RA patients. Retinal venular diameter had significant correlation with disease activity of RA. Retinal imaging is a comparative method for the assessment of microvascular findings of RA patients.

Keywords: Rheumatoid arthritis, Fundus photography, Central retinal arteriolar equivalents, Central retinal venular equivalents

References

1. Wolfe F, Freundlich B, Straus WL. Increase in cardiovascular and cerebrovascular disease prevalence in rheumatoid arthritis. J Rheumatol. 2003; 30:36–40.

2. Turesson C, Jarenros A, Jacobsson L. Increased incidence of cardiovascular disease in patients with rheumatoid arthritis: results from a community based study. Ann Rheum Dis. 2004; 63:952–5.

3. Solomon DH, Karlson EW, Rimm EB, Cannuscio CC, Mandl LA, Manson JE, et al. Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation. 2003; 107:1303–7.

4. Maradit-Kremers H, Nicola PJ, Crowson CS, Ballman KV, Gabriel SE. Cardiovascular death in rheumatoid arthritis: a population-based study. Arthritis Rheum. 2005; 52:722–32.

5. Maradit-Kremers H, Crowson CS, Nicola PJ, Ballman KV, Roger VL, Jacobsen SJ, et al. Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum. 2005; 52:402–11.

6. Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992; 340:1111–5.

7. Alam TA, Seifalian AM, Baker D. A review of methods currently used for assessment of in vivo endothelial function. Eur J Vasc Endovasc Surg. 2005; 29:269–76.

8. Wong TY, Klein R, Sharrett AR, Schmidt MI, Pankow JS, Couper DJ, et al. ARIC Investigators. Retinal arteriolar narrowing and risk of diabetes mellitus in middle-aged persons. JAMA. 2002; 287:2528–33.

9. Cheung N, Wang JJ, Klein R, Couper DJ, Sharrett AR, Wong TY. Diabetic retinopathy and the risk of coronary heart disease: the Atherosclerosis Risk in Communities Study. Diabetes Care. 2007; 30:1742–6.

10. Paoletti R, Gotto AM Jr, Hajjar DP. Inflammation in atherosclerosis and implications for therapy. Circulation. 2004; 109(23 Suppl 1):III20–6.

11. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000; 342:836–43.

12. Kofoed SC, Wittrup HH, Sillesen H, Nordestgaard BG. Fibrinogen predicts ischaemic stroke and advanced atherosclerosis but not echolucent, rupture-prone carotid pla-ques: the Copenhagen City Heart Study. Eur Heart J. 2003; 24:567–76.

13. Roman MJ, Moeller E, Davis A, Paget SA, Crow MK, Lockshin MD, et al. Preclinical carotid atherosclerosis in patients with rheumatoid arthritis. Ann Intern Med. 2006; 144:249–56.

14. Park YB, Ahn CW, Choi HK, Lee SH, In BH, Lee HC, et al. Atherosclerosis in rheumatoid arthritis: morphologic evidence obtained by carotid ultrasound. Arthritis Rheum. 2002; 46:1714–9.

15. Van Doornum S, Strickland G, Kawasaki R, Xie J, Wicks IP, Hodgson LA, et al. Retinal vascular calibre is altered in patients with rheumatoid arthritis: a biomarker of disease activity and cardiovascular risk? Rheumatology (Oxford). 2011; 50:939–43.

16. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988; 31:315–24.

17. Bruce B, Fries JF. The Stanford Health Assessment Questionnaire: dimensions and practical applications. Health Qual Life Outcomes. 2003; 1:20.

18. Prevoo ML, van't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995; 38:44–8.

19. Wong TY, Knudtson MD, Klein R, Klein BE, Meuer SM, Hubbard LD. Computer-assisted measurement of retinal vessel diameters in the Beaver Dam Eye Study: method-ology, correlation between eyes, and effect of refractive errors. Ophthalmology. 2004; 111:1183–90.

20. Lindley RI. Multi-Centre Retinal Stroke Study Collabor-ative Group. Retinal microvascular signs: a key to understanding the underlying pathophysiology of different stroke subtypes? Int J Stroke. 2008; 3:297–305.

21. Wang JJ, Mitchell P, Leung H, Rochtchina E, Wong TY, Klein R. Hypertensive retinal vessel wall signs in a general older population: the Blue Mountains Eye Study. Hypertension. 2003; 42:534–41.

22. Ikram MK, Witteman JC, Vingerling JR, Breteler MM, Hofman A, de Jong PT. Retinal vessel diameters and risk of hypertension: the Rotterdam Study. Hypertension. 2006; 47:189–94.

23. Wong TY, Klein R, Sharrett AR, Duncan BB, Couper DJ, Klein BE, et al. Atherosclerosis Risk in Communities Study. Retinal arteriolar diameter and risk for hypertension. Ann Intern Med. 2004; 140:248–55.

24. Wang JJ, Liew G, Klein R, Rochtchina E, Knudtson MD, Klein BE, et al. Retinal vessel diameter and cardiovascular mortality: pooled data analysis from two older populations. Eur Heart J. 2007; 28:1984–92.

25. Chapman N, Dell'omo G, Sartini MS, Witt N, Hughes A, Thom S, et al. Peripheral vascular disease is associated with abnormal arteriolar diameter relationships at bifurcations in the human retina. Clin Sci (Lond). 2002; 103:111–6.

26. Wong TY, Klein R, Couper DJ, Cooper LS, Shahar E, Hubbard LD, et al. Retinal microvascular abnormalities and incident stroke: the Atherosclerosis Risk in Communities Study. Lancet. 2001; 358:1134–40.

27. Klein R, Sharrett AR, Klein BE, Chambless LE, Cooper LS, Hubbard LD, et al. Are retinal arteriolar abnormalities related to atherosclerosis?: The Atherosclerosis Risk in Communities Study. Arterioscler Thromb Vasc Biol. 2000; 20:1644–50.

28. Liew G, Sharrett AR, Wang JJ, Klein R, Klein BE, Mitchell P, et al. Relative importance of systemic deter- minants of retinal arteriolar and venular caliber: the atherosclerosis risk in communities study. Arch Ophthalmol. 2008; 126:1404–10.

29. de Jong FJ, Ikram MK, Witteman JC, Hofman A, de Jong PT, Breteler MM. Retinal vessel diameters and the role of inflammation in cerebrovascular disease. Ann Neurol. 2007; 61:491–5.

30. Klein R, Klein BE, Knudtson MD, Wong TY, Tsai MY. Are inflammatory factors related to retinal vessel caliber? The Beaver Dam Eye Study. Arch Ophthalmol. 2006; 124:87–94.

31. Chee SP, Jap A, Cheung CM. The prognostic value of angiography in Vogt-Koyanagi-Harada disease. Am J Ophthalmol. 2010; 150:888–93.

32. Isola V, Pece A, Brancato R. Circulatory changes in the choroidal vasculature after verteporfin-based photo-dynamic therapy for choroidal neovascularization in age-related macular degeneration. Retina. 2004; 24:618–20.

Table 1.

Clinical characteristics and parameters of the retinal vascular changes of the study population

	RA patients (n=75)	Control (n=60)	p
Age, yrs	53.1±11.6	52.1±12.0	0.63
Female, n	64 (85%)	51 (85%)	0.99
BMI, kg/m²	22.6±6.4	22.5±8.5	0.87
Disease duration, yrs	2.8±2.6
Systolic blood pressure, mmHg	125.3±11.9	122.3±8.9	0.18
Diastolic blood pressure, mmHg	81.6±11.3	80.4±7.8	0.25
Total cholesterol, mg/dL	198.2±29.7	186.7±22.3	0.23
HsCRP, mmol/L	9.6±12.3
DAS-28	2.6±1.2
CRAE, μm	118.1±31.3	123.8±19.9	0.23
CRVE, μm	162.4±26.4	144.1±23.1	<0.001
AVR	0.70±0.08	0.69±0.08	0.68
AVN, n (mild/severe)	26 (21/5)	8 (7/1)	0.02
FAN, n (mild/severe)	13 (9/4)	9 (8/1)	0.53
OAW, n (mild/severe)	28 (21/7)	19 (19/0)	0.31
Fluorescein angiography features, n
Early pinpoint hyperfluorescence	13 (17%)	2 (3%)	0.01
Areas of delayed choroidal perfusion	3 (4%)	2 (3%)	0.07
Pinpoint peripapillary hyperfluorescence	3 (4%)	0 (0%)	0.17
Disc leakage	3 (4%)	0 (0%)	0.19
Late pooling of fluorescein	2 (3%)	0 (0%)	0.31
Disc hyperfluorescence	1 (1%)	0 (0%)	0.56
Late choroidal hyperfluorescence	1 (1%)	0 (0%)	0.56

RA: rheumatoid arthritis, BMI: body mass index, CRAE: Central retinal arteriolar equivalents, CRVE: Central retinal venular equivalents, AVR: arteriole-to-venule ratio, AVN: arteriovenous nicking, FAN: focal arteriolar narrowing, OAW: opacification of the arteriolar wall.

Table 2.

Characteristics of RA patients with and without AVN

	RA patients with AVN (n=26)	RA patients without AVN (n=49)	p
Age, yrs	56.8±13.2	51.0±10.3	0.04
Disease duration, yrs	3.36±3.31	2.45±2.06	0.22
hsCRP mmol/L	12.44±15.23	10.6±12.72	0.58
Rheumatoid factor, IU/mL	70.72±72.62	71.86±101.60	0.96
DAS 28	2.86±1.34	2.52±1.18	0.26
HAQ	0.51±0.99	0.43±0.58	0.31

All values are presented as mean± SD. RA: rheumatoid arthritis, AVN: arteriovenous nicking, hsCRP: high sensitivity C-reactive protein, DAS 28: disease activity score (28 joints analyzed), HAQ: health assessment questionnaire.

Table 3.

Correlation coefficients (p-value) between the parameters of retinal vascular diameter and clinical parameters of RA group (n=75)

	CRAE	CRVE
Age	0.021 (0.81)	0.037 (0.67)
Duration	0.036 (0.76)	−0.021 (0.86)
hsCRP	0.328 (0.15)	0.438 (<0.001)
Rheumatoid factor	0.159 (0.18)	0.178 (0.13)
DAS 28	−0.027 (0.82)	−0.062 (0.60)
HAQ	0.158 (0.18)	0.138 (0.24)

RA: rheumatoid arthritis, CRAE: central retinal arteriolar equivalents, CRVE: Central retinal venular equivalents, hsCRP: high sensitivity C-reactive protein, DAS 28: disease activity score with 28 joints, HAQ: health assessment questionnaire.

Table 4.

Correlation coefficients between FFA features and clinical parameters of RA group (n=75)

	Early pinpoint hyperfluorescence	Areas of delayed choroidal perfusion	Pinpoint peripapillary hyperfluorescence	Disc leakage	Late pooling of fluorescein	Disc hyperfluorescence	Late choroidal hyperfluorescence
Age	0.201 (0.053)	0.194 (0.095)	0.058 (0.621)	0.111 (0.342)	0.136 (0.246)	0.050 (0.971)	0.090 (0.441)
Duration	−0.053 (0.651)	−0.115 (0.331)	−0.034 (0.773)	−0.088 (0.457)	−0.115 (0.330)	−0.103 (0.383)	−0.049 (0.676)
hsCRP	0.341 (0.003)	0.257 (0.027)	0.099 (0.399)	0.184 (0.117)	0.272 (0.019)	0.196 (0.094)	0.006 (0.958)
Rheumatoid factor	0.037 (0.754)	0.069 (0.562)	0.065 (0.579)	0.005 (0.968)	0.080 (0.490)	0.075 (0.527)	0.145 (0.219)
DAS 28	0.046 (0.700)	0.312 (0.070)	0.022 (0.852)	0.058 (0.648)	0.086 (0.468)	0.035 (0.767)	0.192 (0.101)
HAQ	0.176 (0.134)	0.145 (0.219)	0.094 (0.423)	0.006 (0.963)	0.167 (0.156)	0.030 (0.080)	0.167 (0.156)

FFA: fundus fluorescent angiography, RA: rheumatoid arthritis, hsCRP: high sensitivity C-reactive protein, DAS 28: Disease Activity Score with 28 joints, HAQ: Health Assessment Questionnaire.

Table 5.

Multiple linear regression analysis of CRVE and parameters of arterial stiffness of common carotid artery in RA groups CRVE (R²=0.245, adjusted R²=0.177 in multivariate analysis)

	Univariate analysis				Multivariate analysis
	Coefficient (β)	95% CI	p	R²	Coefficient (β)	95% CI	p
Age	0.077	−0.358 to 0.706	0.516	0.006	0.005	−0.497 to 0.518	0.967
Disease duration	−0,021	−2.629 to 2.195	0.858	−0.013	0.004	−2.289 to 2.363	0.975
hsCRP	0.438	0.443 to 1.265	<0.001	0.181	0.456	0.411 to 1.366	<0.001
Rheumatoid factor	0.178	−0.015 to 0.117	0.130	0.018	0.198	−0.005 to 0.118	0.070
DAS 28	−0.062	−6.324 to 3.665	0.597	−0.010	−0.136	−8.357 to 2.577	0.295
HAQ	0.138	−3.234 to 12.582	0.243	0.005	0.008	−9.305 to 9.881	0.952

RA: rheumatoid arthritis, CRVE: Central retinal venular equivalents, hsCRP: high sensitivity C-reactive protein, DAS 28: Disease Activity Score with 28 joints, HAQ: Health Assessment Questionnaire.

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