Laporan kasus

Myopia Patologi ODS

PEMBIMBING Dr. Cut Masdalena, M.Ked (Oph), Sp.M

DISUSUN OLEHCut Rahmi Nadhia Putri, S.ked

080610028

KEPANITRAAN KLINIK ILMU PENYAKIT MATARUMAH SAKIT UMUM Dr. FAUZIAH BIREUN

PROGRAM STUDI PENDIDIKAN DOKTER UNIVERSITAS MALIKUSSALEH

TAHUN 2014

Jurnal

Hypertensive retinopathy signs as risk indicators of cardiovascular

morbidity and mortality

PEMBIMBING Dr. Cut Masdalena, M.Ked (Oph), Sp.M

DISUSUN OLEHCut Rahmi Nadhia Putri, S.ked

080610028

KEPANITRAAN KLINIK ILMU PENYAKIT MATARUMAH SAKIT UMUM Dr. FAUZIAH BIREUN

PROGRAM STUDI PENDIDIKAN DOKTER UNIVERSITAS MALIKUSSALEH

TAHUN 2014

Hypertensive retinopathy signs as risk indicators of cardiovascular morbidity and

mortality

Abstract

Hypertensive retinopathy has long been regarded as a risk indicator for systemic morbidity and

mortality. New population-based studies show that hypertensive retinopathy signs are strongly

associated with blood pressure, but inconsistently associated with cholesterol and other risk

factors of atherosclerosis. Mild hypertensive retinopathy signs, such as generalized and focal

retinal arteriolar narrowing and arteriovenous nicking, are weakly associated with systemic

vascular diseases. Moderate hypertensive retinopathy signs, such as isolated microaneurysms,

haemorrhages and cotton-wool spots, are strongly associated with subclinical cerebrovascular

disease and predict incident clinical stroke, congestive heart failure and cardiovascular mortality,

independent of blood pressure and other traditional risk factors. These data support the concept

that an assessment of retinal vascular changes may provide further information for vascular risk

stratification in persons with hypertension.

Introduction

The retinal circulation undergoes a series of pathophysiological changes in response to elevated

blood pressure.1 These changes are manifested clinically as a spectrum of signs commonly

referred to as hypertensive retinopathy.2 Hypertensive retinal vascular signs can be broadly

classified into arteriolar changes (generalized arteriolar narrowing, focal arteriolar narrowing,

arteriovenous nicking and arteriolar wall opacification) and more advanced retinopathy lesions

(microaneurysms, blot and flame-shaped haemorrhages, cotton-wool spots, hard exudates and

optic disk swelling). With the exception of disk swelling, these signs can be detected fairly

frequently in adult populations, even in persons without a known history of hypertension.3

The significance of hypertensive retinopathy signs as risk indicators of systemic morbidity and

mortality has long been recognized since their description in patients with renal and

cerebrovascular disease by Marcus Gunn in the late nineteenth century.4,,5 In fact, an assessment

of hypertensive retinopathy signs for risk stratification is supported by international hypertension

management guidelines, including the US Joint National Committee on Prevention, Detection,

Evaluation, and Treatment of High Blood Pressure (JNC) and the British Society of

Hypertension.6,,7 The guidelines emphasize that hypertensive retinopathy, together with left

ventricular hypertrophy and renal impairment, may be considered an indicator of target organ

damage, suggesting that physicians should consider a more aggressive approach in managing

these patients.7

Classification and diagnosis

The traditional classification of hypertensive retinopathy, dating back to 1939, was based on

work by Keith et al.8 Although the modern classification system bears their name, the original

paper8 was not an attempt to classify hypertensive retinopathy signs but to show that severity of

hypertension itself was predictive of mortality. This classification and its modifications typically

consist of four grades of hypertensive retinopathy with increasing severity: grade 1 consists of

‘mild’ generalized retinal arteriolar narrowing; grade 2 consists of ‘more severe’ generalized

narrowing, focal areas of arteriolar narrowing and arteriovenous (AV) nicking; grade 3 consists

of grade 1 and 2 signs plus the presence of retinal haemorrhages, microaneurysms, hard exudates

and cotton-wool spots; grade 4, which is sometimes referred to as accelerated (malignant)

hypertensive retinopathy, consists of signs in the preceding three grades plus optic disk swelling

and macular oedema. Whereas the 3 year survival of persons with grade 1 hypertensive

retinopathy was 70%, the survival was only 6% in those with grade 4 retinopathy.8 The major

limitation of this classification system is the difficulty in distinguishing early hypertensive

retinopathy severity (i.e. grade 1 from grade 2), and several proposals for a new systems have

been made.2,3,,9 A simple three-grade classification is proposed at the end of this article

It is important for the physician to be aware that some of these signs, particularly

microaneurysms, haemorrhages and cotton-wool spots, may also be found in other systemic and

ocular conditions (Table 1). The presence of hard exudates, for example, is more typical of

diabetic retinopathy, while unilateral retinal signs may indicate carotid artery disease. Visual loss

is suggestive of retinal vein occlusion, diabetic retinopathy, accelerated hypertension and other

retinal diseases. Thus, in atypical scenarios, appropriate investigations may be necessary to

exclude these important diseases.

Table 1

Differential diagnoses of isolated retinal haemorrhage, cotton-wool spots and microaneurysms

Epidemiology

Recent population-based studies have provided data on the prevalence of various hypertensive

retinopathy signs in the general population.10–17 Data from these studies indicates that

hypertensive retinopathy signs, defined from retinal photographs, are seen in 3–14% of adult

individuals aged ≥40 years (Fig. 1).

View larger version:

Fig. 1

Prevalence of hypertensive retinopathy: signs and selected population studies.

There are fewer studies of the long-term incidence of new hypertensive retinopathy signs.10 Data

from the Beaver Dam Eye Study, a study of 4926 adults aged 43–86 years in Wisconsin, showed

that the 5 year incidence of focal arteriolar narrowing, AV nicking, retinal haemorrhages and

microaneurysms in people without diabetes ranged from 6% to 10%.

Associations with morbidity and mortality

Blood pressure

An abundance of data from clinical and population-based studies show a strong, graded and

consistent association of hypertensive retinopathy signs with blood pressure (Table 2).10–13,15–17

Both the presence11 and the development of new hypertensive retinopathy signs10 are strongly

related to elevated blood pressure. In the Beaver Dam Eye Study, hypertensive individuals were

50–70% more likely to have retinal haemorrhages and microaneurysms, 30–40% more likely to

have focal arteriolar narrowing and 70–80% more likely to have AV nicking than normotensive

people. In addition, hypertensive persons whose blood pressure was still elevated despite use of

antihypertensive medications, an indication of ‘poorer’ control, were more likely to develop

retinopathy than individuals whose blood pressure was controlled with medication.

Systemic associations of hypertensive retinopathy signs: selected population-based studies

Several recent population-based studies have used standardized retinal photography methods to

define hypertensive retinopathy signs and computer-based imaging methods to measure retinal

arteriolar diameters from photographs. One of these is the Atherosclerosis Risk in Communities

(ARIC) study, a population-based cohort investigation of cardiovascular disease of persons aged

45–64 years selected from four US communities. Retinal photography was added as a component

of the examination and graded for the presence and severity of hypertensive retinal

microvascular changes. The ARIC study demonstrated that generalized retinal arteriolar

narrowing, indicated by narrower arteriolar diameters determined from photographs, was

strongly associated with elevated blood pressure, a finding now confirmed in five other

populations using similar methods.18–22 However, the clinical applicability of these findings is

unclear, as the subtle degree of arteriolar narrowing associated with elevated blood pressure is

difficult to estimate from ophthalmoscopy. For example, each 10 mmHg increase in mean

arterial blood pressure was associated with a reduction of only 6 µm (3%) reduction in retinal

arteriolar diameters in one study.22

Data from ARIC and other studies provides increasing evidence that the pattern of associations

of blood pressure with specific hypertensive retinopathy signs varies. Generalized retinal

arteriolar narrowing and AV nicking appear to be markers of cumulative long-term hypertension

damage, and are independently linked with past blood pressure levels measured 5–8 years before

the retinal assessment.20,21,,23 In contrast, focal arteriolar narrowing, retinal haemorrhages,

microaneurysms and cotton-wool spots reflect more transient changes of acute blood pressure

elevation, and are linked only with concurrent blood pressure measured at the time of the retinal

assessment.20,,21

An important finding in the Beaver Dam Eye Study was the observation that the association

between blood pressure and retinal microvascular signs appears to be weaker with age, 22 possibly

reflecting greater sclerosis of retinal arterioles in older persons.

Atherosclerosis risk factors

In contrast with its strong association with blood pressure, hypertensive retinopathy signs have

not been consistently linked to either direct measures of atherosclerosis, such as carotid artery

stenosis, or atherosclerosis risk factors, such as hyperlipidaemia (Table 2). In the ARIC study,

while controlling for blood pressure, generalized arteriolar narrowing was associated with carotid

artery plaque but not stenosis, AV nicking was associated with carotid artery stenois but not

plaque and focal arteriolar narrowing was not related to either carotid artery measure.12

In the Hoorn Study in The Netherlands hyperglycaemia and abdominal obesity were

independently related to incidence of retinal haemorrhages, microaneurysms, hard exudates and

cotton-wool spots in the non-diabetic general population.24 In the ARIC study, hypertensive

retinopathy signs were related to larger waist circumference, an indicator of abdominal obesity.25

However, not all studies have found associations between hypertensive retinopathy signs and

abdominal obesity or dyslipidaemia.18

The association of hypertensive retinopathy signs with novel atherosclerosis risk factors has also

been investigated. Cross-sectional associations of retinal arteriolar narrowing and AV nicking

with biomarkers of inflammation (e.g. white blood cell counts) and endothelial dysfunction (e.g.

von Willebrand factor) have been reported in the ARIC study12 and by other groups.18

These studies emphasize the fact that typical signs of hypertensive retinopathy may be related to

vascular processes other than blood pressure.

Stroke and cerebrovascular disease

Numerous studies have reported a strong association between various hypertensive retinopathy

signs and both subclinical and clinical cerebrovascular disease26–28 and stroke mortality.29 In the

ARIC study, individuals with retinal haemorrhages, microaneurysms and cotton-wool spots, as

defined from photographs, were two to four times more likely to develop an incident clinical

stroke within 3 years, even when controlling for the effects of blood pressure, cigarette smoking,

lipids and other risk factors.30 Among the participants without stroke or transient ischaemic

attack, hypertensive retinopathy signs were also related to changes in cognitive function, as

defined by standardized neuropsychological tests over a 6 year period,31 and to cerebral white

matter hyperintensity lesions 32 and atrophy, as defined from MRI scans.33

One of the key observations was that the presence of hypertensive retinopathy may offer

additional predictive value of clinical stroke risk in individuals with MRI-defined subclinical

cerebral disease. In the ARIC study, individuals with both MRI-defined white matter lesions and

hypertensive retinopathy were 18 times more likely [relative risk (RR) 18.1; 95% confidence

interval (CI) 5.9–55.4] to develop an incident clinical stroke event than those without either

white matter lesions or hypertensive retinopathy.32

Coronary heart disease and heart failure

Hypertensive retinopathy signs have been linked with both subclinical and clinical coronary

heart disease and congestive heart failure. For example, various hypertensive retinopathy signs

have been associated with ischaemic changes on electrocardiogram,34 severity of coronary artery

stenosis on angiography35 and incident coronary heart disease and myocardial infarction in men36

and women.37

The ARIC study reported that, after controlling for pre-existing risk factors, individuals with

retinal haemorrhages, microaneurysms and cotton-wool spots were twice as likely (RR 1.96;

95% CI 1.52–2.56) to develop congestive heart failure as individuals without retinopathy.38 In

fact, among low-risk individuals (without pre-existing heart disease, diabetes or hypertension),

the presence of hypertensive retinopathy signs predicted a 3-fold increased risk of heart failure

events (RR 2.97, 95% CI 1.49–5.91). This is compatible with the interpretation that

microvascular damage to the myocardium from hypertension and other systemic processes may

be a contributing factor in the development of heart failure.

Other systemic diseases

A number of systemic diseases have been associated with different hypertensive retinopathy

signs (Table 2). In the ARIC study, individuals with AV nicking, retinal haemorrhages,

microaneurysms and cotton-wool spots were more likely to develop renal dysfunction than those

without these signs.39 This association was independent of blood pressure, diabetes and other risk

factors, and was also seen in persons without diabetes or hypertension.

Data from three population-based studies suggest that generalized retinal arteriolar narrowing, a

marker of blood pressure damage, may in fact predict the development of incident

hypertension.40–42 The ARIC study showed that normotensive participants who had generalized

arteriolar narrowing were 60% more likely to be diagnosed with hypertension within a

subsequent 3-year period than normotensive individuals without arteriolar narrowing (RR 1.62;

95% CI 1.21–2.18).41 This association was independent of an individual’s pre-existing blood

pressure levels, body mass index and other known hypertension risk factors.

The ARIC and Beaver Dam Eye Studies have also shown that generalized retinal arteriolar

narrowing predicts the incidence of type 2 diabetes among persons initially free of diabetes,

independent of diabetes risk factors.43,,44 Thus generalized arteriolar narrowing, possibly

reflecting various systemic peripheral arteriolar changes, may be a preclinical marker of overt

hypertension and diabetes.

Cardiovascular mortality

The study by Keith et al.8 was amongst the first to show a dose-dependent increase in mortality

with severity of hypertensive retinopathy changes. Since then, numerous studies conducted in the

1950s and 1960s have further shown that persons with hypertension and retinopathy signs are at

increased risk of mortality.34,45–47 However, inferences from many older studies are limited

because of the subjective evaluation of hypertensive retinopathy signs, the lack of data on cause-

specific mortality rates and inadequate control for potential confounders such as blood pressure

and diabetes.

Nonetheless, more recent studies have provided stronger evidence that hypertensive signs are

markers of mortality risk. In a nested case–control analysis of the Beaver Dam Eye Study,

individuals with retinal microaneurysms and retinal haemorrhages were twice as likely to die

from cardiovascular events as those without these signs.29

Clinical applications

Data from recent studies support the current hypertension guidelines regarding the prognostic

significance of retinopathy signs.6,,7 The information obtained from an assessment of the

retinopathy status appears to be independent of, and qualitatively different from, that of

measuring blood pressure or serum lipids, as the presence of retinopathy signs indicates

susceptibility and the onset of preclinical systemic vascular disease. In particular, it seems that

individuals with certain hypertensive retinopathy signs (e.g. retinal haemorrhages,

microaneurysms and cotton-wool spots) should be more closely monitored for cardiovascular

risk, and may benefit from further investigations (e.g. echocardiogram for heart function) if

clinically indicated.

A three-grade classification system for hypertensive retinopathy is shown in Table 3, and a

suggested approach for patients with various hypertensive retinopathy grades is shown in Figure

2. It is important to emphasize that the management for patients with hypertension and

cardiovascular disease should continue to follow standard risk prediction approaches (i.e. based

on assessment of age and gender of the patient, blood pressure and lipid levels, cigarette smoking

status etc).

Table 3

Classification of hypertensive retinopathy

Fig. 2

Evaluation and management of a patient with hypertensive retinopathy.

The classification in Table 3 groups hypertensive retinopathy signs into mild, moderate and

accelerated (malignant). Patients with mild hypertensive retinopathy signs (Figure 3A) will

probably require routine care, and blood pressure control should be based on established

guidelines.6,,7 Patients with moderate hypertensive retinopathy signs (retinal haemorrhage,

microaneurysm, cotton-wool spots) (Fig. 3B) may benefit from further assessment of vascular

risk (e.g. assessment of cholesterol levels) and, if clinically indicated, appropriate risk reduction

therapy (e.g. cholesterol-lowering agents). Patients with accelerated hypertensive retinopathy

(bilateral disk swelling in the presence of moderate hypertensive retinopathy) (Figure 3C), which

is relatively rare in the general population but may occur in conjunction with severe

hypertension, will continue to need urgent immediate antihypertensive management, including

possible administration of intravenous medication. In such scenarios, physicians should aim for a

small stepwise control of blood pressure over a few hours, and avoid a sudden reduction in blood

pressure which may lead to stroke.

Fig. 3

(A) Mild hypertensive retinopathy: AV nicking (black arrow) and focal narrowing (white arrow).

(B) Moderate hypertensive retinopathy: retinal haemorrhages (black arrows), AV nicking (white

arrow) and generalized retinal arteriolar narrowing. (C) Accelerated (malignant) retinopathy:

swelling of optic disk, retinal haemorrhages and cotton-wool spots.

There have been several experimental studies48,,49 and clinical reports50–52 of regression of

hypertensive retinopathy signs with control of blood pressure. With adequate hypertension

treatment, resolution of hypertensive retinopathy signs may occur over a period of 6 months 52 to

a year.51 Thus follow-up of patients for up to a year after diagnosis may be needed.

These studies also provide some evidence that specifically targeting the microcirculation in

hypertensive individuals may further reduce cardiovascular morbidity and mortality.For

example, certain antihypertensive agents (e.g. ACE inhibitors) have been suggested to have

direct beneficial effects on microvessel structure and function, beyond their primary effect on

lowering blood pressure.52 Therefore such agents may have added therapeutic value in preventing

and treating cardiovascular diseases. However, whether these specific therapies may reverse or

reduce retinopathy changes, and whether this will result in reduced cardiovascular risk, is

currently unclear.

Conclusions

Hypertensive retinopathy signs may differ in their associations with systemic diseases. Isolated

retinal haemorrhages, microaneurysms and cotton-wool spots (moderate hypertensive

retinopathy) appear to be associated with risk of subclinical and clinical stroke, other

cerebrovascular outcomes, congestive heart failure and cardiovascular mortality, independent of

traditional risk factors. In contrast, the systemic associations for generalized retinal arteriolar

narrowing, focal arteriolar narrowing and AV nicking (mild hypertensive retinopathy) appear to

be weaker and less consistent. An assessment of hypertensive retinopathy signs may provide

important information for vascular risk stratification

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Tanda-tanda retinopati hipertensi sebagai indikator risiko morbiditas dan

mortalitas kardiovaskular

abstrak

Retinopati hipertensi telah lama dianggap sebagai indikator risiko morbiditas dan

mortalitas sistemik . Studi berbasis populasi baru menunjukkan bahwa tanda-tanda

retinopati hipertensi yang berkaitan erat dengan tekanan darah , tapi tidak konsisten

terkait dengan kolesterol dan faktor risiko lain dari aterosklerosis . Tanda-tanda

retinopati hipertensi ringan , seperti umum dan focal arteriol retina penyempitan dan

arteriovenosa nicking , yang lemah terkait dengan penyakit pembuluh darah sistemik.

Tanda-tanda retinopati hipertensi moderat, seperti microaneurysms terisolasi,

perdarahan dan cotton-wool spots, yang berkaitan erat dengan penyakit

serebrovaskular subklinis dan memprediksi langkah klinis kejadian , gagal jantung

kongestif dan kematian kardiovaskular , independen dari tekanan darah dan faktor

risiko lainnya . Data ini mendukung konsep bahwa penilaian terhadap perubahan

vaskular retina dapat memberikan informasi lebih lanjut untuk stratifikasi risiko

vaskular pada orang dengan hipertensi.

Sirkulasi retina mengalami serangkaian perubahan patofisiologi dalam

menanggapi tekanan darah. Perubahan ini diwujudkan secara klinis sebagai

spektrum tanda-tanda yang biasa disebut sebagai hipertensi retinopathy. tanda-tanda

pembuluh darah retina hipertensi dapat secara luas diklasifikasikan menjadi

perubahan arteriol ( umum penyempitan arteriolar , focal penyempitan arteriolar ,

arteriovenous nicking dan arteriol dinding kekeruhan ) dan lesi retinopathy lebih

maju ( microaneurysms , noda dan pendarahan berbentuk api , cotton-wool spots ,

eksudat keras dan disk yang optik bengkak ) . Dengan pengecualian disk bengkak ,

tanda-tanda ini dapat dideteksi cukup sering pada populasi dewasa , bahkan pada

orang tanpa riwayat diketahui hypertensi.

Pentingnya tanda-tanda retinopati hipertensi sebagai indikator risiko morbiditas

dan mortalitas sistemik telah lama dikenal sejak deskripsi mereka pada pasien

dengan penyakit ginjal dan serebrovaskular oleh Marcus Gunn pada akhir century.

Ke 19. Bahkan , penilaian tanda-tanda retinopati hipertensi untuk stratifikasi risiko

didukung oleh pedoman manajemen hipertensi internasional , termasuk Komite

Gabungan AS Nasional Pencegahan, Deteksi , Evaluasi , dan Penanganan Tekanan

Darah Tinggi ( JNC ) dan British Society of Hypertension. pedoman menekankan

bahwa retinopati hipertensi , bersama-sama dengan hipertrofi ventrikel kiri dan

gangguan ginjal , dapat dianggap sebagai indikator kerusakan organ target ,

menunjukkan bahwa dokter harus mempertimbangkan pendekatan yang lebih agresif

dalam mengelola pasien.

Klasifikasi dan diagnosis

Klasifikasi tradisional retinopati hipertensi , dating kembali ke 1939 , didasarkan

pada karya Keith et al.8 Meskipun sistem klasifikasi modern yang menyandang nama

mereka, paper8 asli tidak upaya untuk mengklasifikasikan tanda-tanda retinopati

hipertensi tetapi untuk menunjukkan bahwa keparahan hipertensi itu sendiri adalah

prediksi kematian . Klasifikasi ini dan modifikasi yang biasanya terdiri dari empat

kelas retinopati hipertensi dengan meningkatnya keparahan : kelas 1 terdiri dari '

ringan ' umum arteriol retina penyempitan ; kelas 2 terdiri dari ' lebih parah ' umum

penyempitan , area fokus penyempitan arteriolar dan arteriovenosa ( AV ) nicking ;

kelas 3 terdiri dari kelas 1 dan 2 ditambah tanda-tanda adanya pendarahan retina ,

mikroaneurisma , eksudat keras dan cotton-wool spots , kelas 4 , yang kadang-

kadang disebut sebagai dipercepat ( ganas ) retinopati hipertensi , terdiri dari tanda-

tanda di sebelumnya tiga kelas ditambah cakram optik pembengkakan dan edema

makula . Sedangkan survival 3 tahun orang dengan kelas 1 retinopati hipertensi

adalah 70 % , kelangsungan hidup hanya 6 % pada mereka dengan kelas 4

retinopathy.

Hal ini penting bagi dokter untuk menyadari bahwa beberapa dari tanda-tanda

ini, khususnya microaneurysms , perdarahan dan cotton-wool spots , juga dapat

ditemukan dalam kondisi sistemik dan okular lainnya ( Tabel 1 ) . Kehadiran eksudat

keras , misalnya , lebih khas retinopati diabetes , sedangkan tanda-tanda retina

unilateral dapat menunjukkan penyakit arteri karotid . Kehilangan penglihatan adalah

sugestif dari oklusi vena retina , retinopati diabetes , hipertensi dipercepat dan

penyakit retina lainnya . Dengan demikian , dalam skenario atipikal , penyelidikan

yang tepat mungkin diperlukan untuk mengecualikan penyakit penting ini .

Diagnosis banding perdarahan retina terisolasi , cotton-wool spots dan

mikroaneurisma

Studi berbasis populasi baru-baru ini telah memberikan data prevalensi berbagai

tanda retinopati hipertensi pada umumnya data population.10 - 17 dari studi ini

menunjukkan bahwa tanda-tanda retinopati hipertensi , yang didefinisikan dari foto-

foto retina , terlihat dalam 3-14 % dari individu dewasa berusia ≥ 40 tahun prevalensi

retinopati hipertensi : tanda-tanda dan studi populasi yang dipilih.

Ada penelitian lebih sedikit dari kejadian jangka panjang Data retinopati

hipertensi baru signs.10 dari Beaver Dam Eye Study , sebuah studi dari 4926 orang

dewasa berusia 43-86 tahun di Wisconsin , menunjukkan bahwa kejadian 5 tahun

focal penyempitan arteriolar , AV nicking , perdarahan retina dan mikroaneurisma

pada orang tanpa diabetes berkisar antara 6 % sampai 10 %.

Asosiasi dengan morbiditas dan mortalitas tekanan darah kumpulan data dari studi

klinis dan berbasis populasi menunjukkan kuat , dinilai dan konsisten asosiasi tanda-

tanda retinopati hipertensi dengan tekanan darah ( Tabel 2 ) .10-13,15-17 Baik

presence dan pengembangan retinopati hipertensi baru yang gejala sangat terkait

dengan tekanan darah tinggi . Dalam Beaver Dam Eye Study , individu hipertensi

adalah 50-70 % lebih mungkin untuk memiliki pendarahan retina dan

mikroaneurisma , 30-40 % lebih mungkin untuk memiliki focal penyempitan

arteriolar dan 70-80 % lebih mungkin untuk memiliki AV nicking daripada orang

normotensif . Selain itu, orang-orang yang hipertensi yang tekanan darah masih

tinggi meskipun penggunaan obat antihipertensi , indikasi control ' miskin ' , lebih

mungkin untuk mengembangkan retinopati daripada individu yang tekanan darah

dikendalikan dengan obat-obatan .

Asosiasi sistemik tanda-tanda retinopati hipertensi : studi berbasis populasi yang

dipilih, Beberapa studi berbasis populasi baru-baru ini telah menggunakan metode

fotografi retina standar untuk menentukan tanda-tanda retinopati hipertensi dan

metode pencitraan berbasis komputer untuk mengukur diameter arteriol retina dari

foto . Salah satunya adalah Atherosclerosis Risk in Communities ( ARIC ) studi ,

yang berdasarkan populasi kohort investigasi penyakit kardiovaskular dari orang

yang berusia 45-64 tahun yang dipilih dari empat komunitas AS . Fotografi retinal

ditambahkan sebagai komponen pemeriksaan dan dinilai untuk kehadiran dan tingkat

keparahan hipertensi perubahan mikrovaskuler retina . Penelitian ARIC

menunjukkan bahwa umum retina penyempitan arteriolar , ditunjukkan dengan

diameter arteriol sempit ditentukan dari foto-foto , sangat terkait dengan tekanan

darah tinggi , sebuah temuan sekarang dikonfirmasi dalam lima populasi lain dengan

menggunakan sejenis methods.18 - 22 Namun , penerapan klinis dari temuan ini

tidak jelas , seperti tingkat halus penyempitan arteriolar berhubungan dengan tekanan

darah tinggi adalah sulit untuk memperkirakan dari oftalmoskopi . Sebagai contoh,

setiap peningkatan 10 mmHg tekanan darah arteri rata-rata dikaitkan dengan

penurunan hanya 6 m ( 3 % ) pengurangan diameter arteriol retina dalam satu study.

Data dari ARIC dan studi lain memberikan peningkatan bukti bahwa pola asosiasi

tekanan darah dengan tanda-tanda retinopati hipertensi tertentu bervariasi .

Generalized arteriol retina penyempitan dan AV nicking tampaknya penanda

kerusakan jangka panjang hipertensi kumulatif , dan secara independen terkait

dengan tingkat tekanan darah lalu diukur 5-8 tahun sebelum assessment.20 retina , 21

,Sebaliknya , fokus penyempitan arteriolar , pendarahan retina , dan mikroaneurisma

cotton-wool spots mencerminkan perubahan yang lebih transien peningkatan tekanan

darah akut , dan dihubungkan hanya dengan tekanan darah bersamaan diukur pada

saat assessment. retina

Temuan penting dalam Beaver Dam Eye Study adalah pengamatan bahwa

hubungan antara tekanan darah dan tanda-tanda mikrovaskuler retina tampaknya

lemah dengan usia , 22 mungkin mencerminkan sclerosis lebih besar dari arteriol

retina pada orang tua .

Faktor risiko Aterosklerosis

Berbeda dengan hubungan yang kuat dengan tekanan darah , tanda-tanda

retinopati hipertensi belum konsisten terkait dengan baik langkah-langkah langsung

aterosklerosis , seperti stenosis arteri karotis , atau faktor risiko aterosklerosis ,

seperti hiperlipidemia ( Tabel 2 ) . Dalam studi ARIC , sekaligus mengontrol tekanan

darah , penyempitan arteriolar umum dikaitkan dengan plak arteri karotid tetapi tidak

stenosis , AV nicking dikaitkan dengan stenois arteri karotis tapi tidak plak dan fokus

penyempitan arteriolar tidak terkait dengan baik measure.12 arteri karotid

Dalam Studi Hoorn di Belanda hiperglikemia dan obesitas perut secara

independen terkait dengan kejadian pendarahan retina , mikroaneurisma , eksudat

keras dan cotton-wool spots di population. umum non - diabetes Dalam studi ARIC ,

tanda-tanda retinopati hipertensi terkait dengan lebih besar lingkar pinggang ,

indikator obesitas. Namun, tidak semua studi telah menemukan hubungan antara

tanda-tanda retinopati hipertensi dan obesitas abdominal atau dyslipidaemia.

Hubungan tanda-tanda retinopati hipertensi dengan faktor risiko aterosklerosis

baru juga telah diteliti . Asosiasi cross- sectional dari retina penyempitan arteriolar

dan AV nicking dengan biomarker peradangan ( misalnya jumlah sel darah putih )

dan disfungsi endotel ( misalnya faktor von Willebrand ) telah dilaporkan dalam

study12 ARIC dan oleh groups.

Studi ini menekankan fakta bahwa tanda-tanda khas dari retinopati hipertensi

mungkin berhubungan dengan proses vaskular selain tekanan darah .

Stroke dan penyakit serebrovaskular

Sejumlah penelitian telah melaporkan hubungan yang kuat antara berbagai tanda-

tanda retinopati hipertensi dan kedua subklinis dan klinis serebrovaskular disease26 -

28 dan stroke mortality.29 Dalam studi ARIC , individu dengan pendarahan retina ,

dan mikroaneurisma cotton-wool spots , sebagaimana didefinisikan dari foto , dua

sampai empat kali lebih mungkin untuk mengembangkan stroke klinis insiden dalam

waktu 3 tahun , bahkan ketika mengendalikan untuk efek dari tekanan darah ,

merokok , lipid dan factors.30 risiko lain antara peserta tanpa stroke atau transient

ischemic attack , tanda-tanda retinopati hipertensi juga terkait dengan perubahan

fungsi kognitif , seperti yang didefinisikan oleh tes neuropsikologi standar selama 6

tahun , 31 dan cerebral hyperintensity materi putih lesi 32 dan atrofi , sebagaimana

didefinisikan dari MRI scans.

Salah satu pengamatan penting adalah bahwa kehadiran retinopati hipertensi

mungkin menawarkan nilai prediksi tambahan risiko stroke klinis pada individu

dengan MRI - didefinisikan penyakit otak subklinis . Dalam studi ARIC , individu

dengan baik lesi materi putih MRI - didefinisikan dan retinopati hipertensi adalah 18

kali lebih mungkin [ risiko relatif ( RR ) 18,1 ; selang kepercayaan 95% ( CI ), untuk

kejadian stroke yang klinis insiden dibandingkan tanpa baik lesi materi putih atau

retinopathy.hipertensi. Penyakit jantung koroner dan gagal jantung.

Tanda-tanda retinopati hipertensi telah dikaitkan dengan kedua penyakit jantung

koroner subklinis dan klinis dan gagal jantung kongestif . Sebagai contoh, berbagai

tanda-tanda retinopati hipertensi telah dikaitkan dengan perubahan iskemik pada

elektrokardiogram , 34 keparahan stenosis arteri koroner pada angiography35 dan

insiden penyakit jantung koroner dan infark miokard pada men36 dan women.

Penelitian ARIC melaporkan bahwa , setelah mengendalikan faktor risiko yang

sudah ada sebelumnya , individu dengan pendarahan retina , dan mikroaneurisma

cotton-wool spots dua kali lebih mungkin ( RR 1,96 , 95 % CI 1,52-2,56 ) untuk

mengembangkan gagal jantung kongestif sebagai individu tanpa retinopati .38

Bahkan, di antara individu yang berisiko rendah ( tanpa penyakit jantung yang sudah

ada sebelumnya , diabetes atau hipertensi ) , kehadiran tanda-tanda retinopati

hipertensi memprediksi risiko 3 kali lipat peningkatan kejadian gagal jantung ( RR

2,97 , 95 % CI 1,49-5,91 ) . Ini kompatibel dengan interpretasi bahwa kerusakan

mikrovaskuler ke miokardium dari hipertensi dan proses sistemik lainnya dapat

menjadi faktor yang berkontribusi dalam pengembangan gagal jantung .

Penyakit sistemik lainnya

Sejumlah penyakit sistemik telah dikaitkan dengan tanda-tanda hipertensi

retinopati yang berbeda. Dalam studi ARIC , individu dengan nicking AV ,

pendarahan retina , dan mikroaneurisma cotton-wool spots lebih mungkin untuk

mengembangkan disfungsi ginjal daripada mereka yang tidak ada gejala. Asosiasi ini

adalah independen dari tekanan darah , diabetes dan faktor risiko lain , dan juga

terlihat pada orang tanpa diabetes atau hipertensi .

Data dari tiga studi berbasis populasi menunjukkan bahwa umum penyempitan

arteriol retina , penanda kerusakan tekanan darah , mungkin sebenarnya memprediksi

perkembangan insiden studi hypertension. The ARIC menunjukkan bahwa peserta

normotensif yang umum penyempitan arteriolar adalah 60 % lebih mungkin

didiagnosis dengan hipertensi dalam jangka waktu 3 tahun berikutnya dibandingkan

orang normotensif tanpa penyempitan arteriolar ( RR 1,62 , 95 % CI 1,21-2,18 )

asosiasi ini adalah independen dari yang sudah ada tingkat tekanan darah

individu ,indeks massa tubuh dan faktor lain yang diketahui hipertensi risiko .

The ARIC dan Beaver Dam Eye Studi juga menunjukkan bahwa umum arteriol

retina penyempitan memprediksi kejadian diabetes tipe 2 di antara orang-orang yang

pada awalnya bebas dari diabetes , independen factors. risiko diabetes , Dengan

demikian umumnya penyempitan arteriolar , mungkin mencerminkan berbagai

arteriol perifer sistemik perubahan , dapat menjadi penanda praklinis hipertensi

terbuka dan diabetes mortalitas kardiovaskular.

Penelitian oleh Keith et al.8 adalah di antara yang pertama untuk menunjukkan

peningkatan mortalitas dengan keparahan perubahan retinopati hipertensi . Sejak itu,

sejumlah studi yang dilakukan pada 1950-an dan 1960-an telah lebih lanjut

menunjukkan bahwa orang dengan hipertensi dan retinopathy tanda-tanda berada

pada peningkatan risiko mortality.34 ,45 - 47 Namun , kesimpulan dari banyak studi

yang lebih tua terbatas karena evaluasi subjektif dari retinopati hipertensi tanda-tanda

, kurangnya data pada tingkat penyebab kematian - spesifik dan kontrol yang tidak

memadai untuk pembaur potensial seperti tekanan darah dan diabetes .

Meskipun demikian , penelitian yang lebih baru telah memberikan bukti kuat

bahwa tanda-tanda hipertensi merupakan penanda risiko kematian . Dalam analisis

kasus-kontrol berumber dari Beaver Dam Eye Study , individu dengan

microaneurysms retina dan pendarahan retina dua kali lebih mungkin untuk

meninggal akibat kejadian kardiovaskular seperti yang tanpa gejala.

Data dari studi terbaru mendukung pedoman hipertensi saat ini tentang

pentingnya prognostik retinopati signs. Informasi yang diperoleh dari penilaian status

retinopathy tampaknya independen , dan secara kualitatif berbeda , yang mengukur

tekanan darah atau serum lipid , sebagai tanda-tanda retinopati menunjukkan

kerentanan dan timbulnya penyakit vaskular sistemik praklinis . Secara khusus,

tampaknya bahwa individu dengan tanda-tanda retinopati hipertensi tertentu

( misalnya pendarahan retina , dan mikroaneurisma cotton-wool spots ) harus

dipantau lebih dekat untuk risiko kardiovaskular , dan dapat mengambil manfaat dari

penyelidikan lebih lanjut ( misalnya echocardiogram untuk fungsi jantung ) jika

terindikasi secara klinis .

Sebuah sistem klasifikasi tiga kelas untuk retinopati hipertensi ditunjukkan pada

Tabel 3 , dan pendekatan yang disarankan untuk pasien dengan berbagai kelas

retinopati hipertensi ditunjukkan pada Gambar 2 . Adalah penting untuk menekankan

bahwa manajemen untuk pasien dengan hipertensi dan penyakit kardiovaskular harus

terus mengikuti pendekatan standar prediksi risiko ( yaitu berdasarkan penilaian dari

usia dan jenis kelamin pasien , tekanan darah dan kadar lipid , rokok status merokok

dll ) .

Evaluasi dan pengelolaan pasien dengan retinopati hipertensi.

Klasifikasi pada Tabel 3 kelompok hipertensif tanda-tanda retinopati menjadi

ringan, sedang dan dipercepat ( ganas ) . Pasien dengan tanda-tanda retinopati

hipertensi ringan ( Gambar 3A ) mungkin akan memerlukan perawatan rutin , dan

kontrol tekanan darah harus didasarkan pada didirikan guidelines. Pasien dengan

tanda-tanda retinopati hipertensi sedang ( perdarahan retina , microaneurysm ,

cotton-wool spots ) ( Gambar . 3B ) dapat mengambil manfaat dari penilaian lebih

lanjut dari risiko vaskular ( misalnya penilaian kadar kolesterol ) dan , jika terindikasi

secara klinis , terapi pengurangan risiko yang sesuai (misalnya agen penurun

kolesterol ) . Pasien dengan retinopati hipertensi dipercepat ( bilateral disk yang

bengkak di hadapan hipertensi retinopati moderat ) ( Gambar 3C ) , yang relatif

jarang terjadi di populasi umum tetapi dapat terjadi dalam hubungannya dengan

hipertensi berat , akan terus membutuhkan manajemen antihipertensi segera

mendesak , termasuk kemungkinan pemberian obat intravena. Dalam skenario seperti

ini , dokter harus bertujuan untuk kontrol bertahap kecil tekanan darah selama

beberapa jam , dan menghindari penurunan mendadak tekanan darah yang dapat

menyebabkan stroke.

Ada beberapa studies eksperimental dan laporan klinis regresi tanda-tanda

retinopati hipertensi dengan kontrol tekanan darah . Dengan pengobatan hipertensi

yang memadai , resolusi tanda-tanda retinopati hipertensi dapat terjadi selama

periode 6 bulan hingga tahun yang demikian tindak lanjut dari pasien sampai satu

tahun setelah diagnosis mungkin diperlukan.

Studi ini juga menyediakan beberapa bukti yang secara khusus menargetkan

mikrosirkulasi pada individu hipertensi dapat mengurangi morbiditas kardiovaskular

dan mortality. contoh , agen antihipertensi tertentu (misalnya inhibitor ACE ) telah

disarankan untuk memiliki efek menguntungkan langsung pada struktur microvessel

dan fungsi , di luar utama mereka efek pada menurunkan tekanan darah. Oleh karena

agen tersebut mungkin telah menambahkan nilai terapeutik dalam mencegah dan

mengobati penyakit jantung . Namun, apakah ini terapi khusus dapat membalikkan

atau mengurangi perubahan retinopati , dan apakah ini akan mengakibatkan risiko

kardiovaskular berkurang , saat ini tidak jelas.

kesimpulan

Tanda-tanda retinopati hipertensi mungkin berbeda dalam asosiasi mereka dengan

penyakit sistemik . Pendarahan retina terisolasi , dan mikroaneurisma cotton-wool

spots ( retinopati hipertensi moderat ) tampaknya terkait dengan risiko subklinis dan

klinis stroke, hasil serebrovaskular lainnya , gagal jantung kongestif dan kematian

kardiovaskular , independen dari faktor risiko tradisional . Sebaliknya , asosiasi

sistemik untuk umum penyempitan arteriol retina , focal penyempitan arteriolar dan

AV nicking ( retinopati hipertensi ringan) tampaknya lebih rendah konsisten.

Penilaian terhadap tanda-tanda retinopati hipertensi dapat memberikan informasi

penting untuk stratifikasi risiko vaskular.