ASST Spedali Civili di Brescia – University of Brescia, Italy

La circolazione retinica e

il rischio cardiovascolare

Prof. ENRICO AGABITI ROSEI

Clinica Medica – University of Brescia, Italy

• Arteriolar vasoconstriction

• Increase in wall : lumen ratio

• Rarefaction

MAIN ALTERATIONS OF MICROCIRCULATION

IN HYPERTENSION

Histological Similarities Cerebral Arteries – Retinal Arteries

cerebral artery retinal artery

200 times

Coutesy of K. Amann, Universität Erlangen-Nürnberg, 2003

Cerebral and retinal circulation share anatomic, physiological, and embryological features

(Wong TY, Mitchell P. Hypertensive retinopathy. N Engl J Med 2004; 351:2310-2317)

Classification of hypertensive changes in the retina in a severity scale, according

to Keith- Wegener-Barker grading system, subsequently modified by Scheie

N. M Keith, H. P. Wegener, and N. W. Barker, Some different types of essential hypertension: their course and prognosis, American Journal of

Medicine Science 197 (1939), 336–354.

H. G. Scheie, Evaluation of ophthalmoscopic changes of hypertension and arterial sclerosis, Archives of Ophthalmology 49 (1953), no. 2, 117–

138.

A patent–pending optical accessory is magnetically attached to the

smartphone to convey and filter the smartphone’s LED light coaxially to

the camera to capture video and still retinal images with a field of view up

to 25 degrees.

• Samsung Galaxy S4

• Samsung Galaxy S5

• iPhone 5/5S, 6

A new approach – Optical Device

A Smartphone Attachment for Portable Ophthalmoscopy (D-Eye)

Wong TY and coll, JAMA 2002, 287: 1153-1159

Wong TY and coll, JAMA 2002, 287: 1153-1159

THE END THE END Large scale, population based studies assessing associations between

retinal vascular caliber (based on retinal photography) and blood pressure,

target organ damage and cardiovascular risk (part 1)

Ott & Schmieder, 2014, modified

THE END Large scale, population based studies assessing associations between

retinal vascular caliber (based on retinal photography) and blood pressure,

target organ damage and cardiovascular risk (part 2)

Ott & Schmieder, 2014, modified

Quantification of topological changes in retinal vascular

architecture in essential and malignant hypertension

Hughes AD et al, J Hypertens 2006, 24:889–894

EHT was associated with an increase in the arteriolar length-to-

diameter ratio (P < 0.01). There were also alterations in

arteriolar topology indicative of rarefaction, including a marked

reduction in the number of terminal branches in EHT (P < 0.01).

These changes in the arteriolar network were exaggerated in

MHT and there was also increased venular tortuosity and

venular rarefaction in MHT compared with normotensive

subjects.

Hypertension is associated with marked topological alterations in

the retinal vasculature, and quantification of these changes may

be a useful novel approach to the assessment of target organ

damage in hypertension.

Retinal Microvasculature as a Model to Study the

Manifestations of Hypertension

Cheung CY et al Hypertension 2012; 60:1094-1103

Amplification of hypertensive stimuli

and maintenance of high blood pressure

Reduction in organ flow reserve

(at maximal vasodilatation)

Early generalized phenomenon

Strong predictor of CV events

Reduced by antihypertensive treatment

Microcirculation in hypertension :

Remodeling of small resistance arteries

Evaluation of retinal arteriole morphology by scanning laser Doppler

flowmetry and automatic full-field perfusion imaging analysis

Non-invasive measurement of internal diameter (ID),

external diameter (ED), wall thickness, wall to lumen

ratio (W/L) and wall cross-sectional area (WCSA) of

retinal arterioles using scanning laser doppler flowmetry

(SLDF) was performed (Heidelberg Retina Flowmeter,

Heidelberg Engineering).

Heidelberg Retina Flowmeter,

Heidelberg Engineering

Harazny J et al. Hypertension 2007;50:623-629

Correlation between systolic or diastolic blood pressure and wall-to-lumen ratio of retinal arterioles

Correlation between systolic blood pressure and wall-to-lumen ratio of

retinal arterioles (r=0.360, P=0.010).

In multiple regression analysis: b=0.42, p=0.012

Correlation between diastolic blood pressure and wall-to-lumen ratio

of retinal arterioles (r=0.536, P<0.001).

In mulitple regression analysis: b=0.55, p<0.001

Ritt M et al. J Hypertens 2008;26:1427-1434

Evaluation of small retinal artery morphology by scanning laser Doppler

flowmetry and automatic full-field perfusion imaging analysis

Clinica Medica, University of Brescia, Italy

Close correlation between wall to lumen ratio (W/L) of retinal arterioles and

media to lumen ratio of subcutaneous small arteries (M/L) in a population of

normotensive subjects (n=16) and hypertensive patients (n=24)

Rizzoni D, Agabiti Rosei E et al, J Hypertens, 2012

r=0.76, p<0.001

y = 6,9364x - 0,2779

R2 = 0,5702

0,00

0,10

0,20

0,30

0,40

0,50

0,60

0,70

0,80

0,04 0,06 0,08 0,10 0,12 0,14 0,16

M/L

W/L

295 subjects

147males and 148 females

age range 22-72 years mean 54 + 7

119 normotensives

176 essential hypertensive patients (100 treated)

Out of 322 individuals, the retinal measurements could not be performed because of refraction problems in 27 subjects

Patients

Hypertension, 2014

Correlation between WLR and PWV

r =0.17 , p = 0.005

Salvetti, Agabiti Rosei et al, Hypertension, 2014

Multivariate analysis

Dependent Variable: WLR

Beta Sig

24 hrs MBP 0.003 0.001 PWV m/sec 0.010 0.005 Age 0.029 0.612 BMI kg/m2 0.056 0.325 Fasting glucose mg/dl 0.019 0.744 LDL-cholesterol mg/dl - 0.028 0.62 e GFR ml/min/1.73 - 0.055 0.339

Hypertension , 2014 Salvetti, Agabiti Rosei et al, Hypertension, 2014

* P<0.05, ** P<0.01 vs. Basal, # P<0.05 vs. Lercanidipine alone (4 weeks)

**

Basal

Lercanidipine (4 weeks)

Lercanidipine+ENA

(24 weeks)

**

Basal

Lercanidipine (4 weeks)

Lercanidipine+HCTZ

(24 weeks)

Reduction in wall to lumen ratio of retinal arterioles after lercanidipine+enalapril

treatment (n=10) and after lercanidipine+hydrochlorothiazide treatment in

hypertensive patients (n=10)

* P<0.05, ** P<0.01 vs. Basal, # P<0.05 vs. Lercanidipine alone (4 weeks)

***#

**

Basal

Lercanidipine (4 weeks)

Lercanidipine+ENA

(24 weeks)

**

** Basal

Lercanidipine (4 weeks)

Lercanidipine+HCTZ

(24 weeks)

Reduction in wall to lumen ratio of retinal arterioles after lercanidipine+enalapril

treatment (n=10) and after lercanidipine+hydrochlorothiazide treatment in

hypertensive patients (n=10)

Schematic outline of adaptive optics imaging system. A beam of light enters the eye, and a small amount is

reflected back out of the eye and into the optical system. Reflected light is altered by the deformable mirror

for optical aberrations based on measurements made by the wave-front senor. Information about the

aberrations of the wave front is processed by the control system that provides feedback to the deformable

mirror

J Hypertens 2014 ; 32(4):890-898

Morphometric analysis of small arteries in the human retina using adaptive

optics imaging: relationship with blood pressure and focal vascular

changes. Koch E, Rosenbaum D, Brolly A, Sahel JA, Chaumet-Riffaud P, Girerd X, Rossant F, Paques M.

Thus, the reproducibility of the morphological parameters measured (1.3% for internal diameter, 3.7% for the wall cross-sectional area, and 3.2% for WLR) (1) is far lower than that observed with scanning laser Doppler flowmetry (less than

10%) (2).

1) Rosenbaum D, Koch E, Girerd X, Rossant F, Paˆques M. Imaging of retinal arteries with adaptative optics, feasibility and reproducibility. Ann Cardiol Angeiol (Paris) 2013; 62:184–188.

2) Harazny JM, Faff U, Welzenbach J, Ott C, Ritt M, Lehmann M, et al. New AQ8 software analyses increases the reliability of measurement of retinal arterioles morphology by scanning laser Doppler flowmetry in humans. J Hypertens 2011; 29:777–782.

EFFECTS OF AGE, BLOOD PRESSURE AND ANTIHYPERTENSIVE

TREATMENTS ON RETINAL ARTERIOLES REMODELING ASSESSED

BY ADAPTIVE OPTICS

Rosembaum D et al , J Hypertens, in press

CONCLUSIONS

…. new technologies, presently under clinical

evaluation, may help us in the near future to:

• non invasively assess microvascular structural

alterations

• better stratify cardiovascular risk of our patients

with consequent optimization of treatment.

Eyes: an open window on our inner body “ ”

THE END

Patent Pending – Optical Device

+ 8 D

+18 D

-10 D

Smartphone Focusing Range

0

- 10 D 0 D

Representative Retinal Images

Representative retinal images taken with D-Eye.

(A) Normal optic disc in an undilated child. (B)

Normal posterior pole in a dilated 29-year-old

woman. (C) Dry age-related maculopathy in an

undilated 75-year-old man. (D) Optic nerve glioma

in a 23-year-old undilated woman. (E) Posterior

vitreous detachment in a dilated 72-year-old

pseudophakic woman. (F) Waxy disc pallor and

pigmentary changes in a 50-year-old man with

retinitis pigmentosa.

Cross-polarization-accentuated

nerve-fiber layer definition (white

arrows).

Comparison of Smartphone Ophthalmoscopy with Slit-lamp Biomicroscopy for Grading Diabetic Retinopathy

Andrea Russo, MD, et al. Received: August 28, 2014; Received in revised form: October 30, 2014; Accepted: November 2, 2014;

Published Online: November 07, 2014

Scanning Laser Doppler Flowmetry:

A tool to assess structural components

Laser class I, 690 nm

energy 0.1 mW

10-20° picture,

confocal 3D 2D

Resolution:

3D: 10 x 10 x 300 µm

2D: 10 x 10 µm

Duration of scanning : 2.048s

Intraobserver variation:

Coefficient of variation:

4.95%

Interobserver variation:

Coefficient of variation:

7.96%

THE END THE END Large scale, population based studies assessing associations between

retinal vascular caliber (based on retinal photography) and blood pressure,

target organ damage and cardiovascular risk (part 1)

Ott & Schmieder, 2014, modified

THE END

THE END