he ophthalmoscope (Figure 1), which was in-vented in 1850 by Hermann von Helmholtz,1

allowed for the clinical correlation of retinalfindings with many systemic diseases, such as

diabetes mellitus, hypertension, hyperlipidemia, thy-roid disease, vascular disease, and systemic infections.Although ocular signs are not necessarily disease specif-ic (eg, signs seen in hypertensive patients also appearin diabetic patients), early recognition of these signscan help prevent unnecessary vision loss.2 Additionally,these signs in combination can help the physiciandetermine which systemic disease is responsible for thepatients retinopathy. A comprehensive discussion ofall systemic diseases with ocular manifestations is be-yond the scope of this article. Hence, this review focus-es on retinal findings associated with two of the mostcommon diseases seen in primary care: diabetes melli-tus and hypertension. A brief review of the techniquefor ocular examination with the ophthalmoscope alsois included.

OCULAR EXAMINATION

A systematic routine should be used when examin-ing the eyes and surrounding tissues.2,3 Generally, it isbest to examine the eyes in the following sequence:visual acuity, extraocular muscle function, visual fieldtesting, and then finally ophthalmoscopy.4,5 For opti-mum retinal examination, a mydriatic agent is used todilate the pupil.2 Both tropicamide 1% (Mydriacyl) andphenylephrine hydrochloride 2.5% (Mydfrin) dilatethe pupils in approximately 30 minutes. Once the pa-tients eyes are dilated, the ophthalmoscope is heldapproximately 12 to 15 cm away from the patients eye.For examining the patients right eye, the examinerholds the ophthalmoscope in close proximity to his orher own right eye using the right hand. For examiningthe patients left eye, the examiner uses the left handand left eye. The examiner then moves in closer to thepatients eye while adjusting the lens settings for opti-

mal focus. The physician also should keep his or hernonexamining eye open during this procedure.

DIABETES MELLITUS

Diabetes mellitus is the leading cause of new cases ofblindness in middle-aged Americans.6,7 Timely detec-tion and treatment of diabetic retinopathy can substan-tially reduce the likelihood of blindness. Approximatelyhalf of adult diabetics in the United States, however, donot receive yearly eye examinations.8

Type 2 diabetes mellitus is more common than type 1diabetes, and the prevalence of type 2 diabetes increaseswith age. Type 2 diabetes may remain undetected for along time. It has been estimated that 5 to 10 years of sus-tained hyperglycemia are needed to develop retinalmanifestations.6 A high degree of correlation existsbetween glycemic control as measured by glycosylatedhemoglobin levels and presence of early retinopathic

T

Dr. Gunderson is as Assistant Professor of Medicine and Director ofPediatric Ophthalmology and Adult Strabismus, University of TexasMedical Branch, Galveston, TX. Dr. Karnath is an Assistant Professorof Internal Medicine, University of Texas Medical Branch.

www.turner-white.com Hospital Physician November 2003 15

R e v i e w o f C l i n i c a l S i g n s

Series Editor: Bernard Karnath, MD

Retinal Manifestations of Diabetes Mellitus and Hypertension

Charlise A. Gunderson, MDBernard Karnath, MD

RETINAL SIGNS OF DIABETES AND HYPERTENSION

Microaneurysms Dot and blot hemorrhagesHard exudates Macular edema Cotton-wool spotsNeovascularization Retinal edema Optic disc edema

changes. As a rule, retinopathy precedes nephropathy.Therefore, early detection of the ocular manifestationsof diabetes (Table 1) is important.9

The initial stage of retinal changes in the diabeticpatient is called nonproliferative diabetic retinopathy9,10

and includes the appearance of dot and blot hemor-rhages (which are caused by intraretinal blood) and/ormicroaneurysms (Figure 2). Microaneurysms are seenas scattered red spots in the retina caused by weakenedarterioles and capillaries leading to outpouching of thevessel walls. Dot and blot hemorrhages represent bloodin the retina. The differentiation between a micro-aneurysm and a dot and a blot hemorrhage is basedon size and is somewhat subjective. Distinguishing be-tween a dot and blot hemorrhage and microaneurysmon direct ophthalmoscopy may be difficult.

Several years may pass before other lesions, such asretinal hemorrhages and exudates, develop.10,11 Hardexudates caused by leakage of proteins and lipids fromthe damaged arterioles appear as small white or yellowareas with sharp margins, often with a glistening ap-pearance on the retina (Figure 3). As the disease pro-gresses further, retinal changes occur, including macularedema and cotton-wool spots (Figure 4). Cotton-woolspots result from microinfarctions of nerve fibers causedby focal ischemia after occlusion of terminal retinal arte-rioles occurs. These spots appear as white fluffy spots onthe retina. Macular edema is the principal mechanismof visual loss in nonproliferative retinopathy. Macularedema results from leakage from microaneurysms.

Proliferative diabetic retinopathy is a late stage ofdisease and is characterized by neovascularization (ie,new blood vessel formation), which is a response tocontinued retinal ischemia.9 Neovascularization resultsin vision loss due to vitreous hemorrhages and retinaldetachment.

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Figure 1. A drawing of Hermann von Helmholtzs originalophthalmoscope. (Reprinted with permission from Ravin JG.Sesquicentennial of the ophthalmoscope. Arch Ophthalmol1999;117:1636.)

Figure 2. The arrow indicates dot and blot hemorrhages.Hard exudates also are visible.

Figure 3. The arrow indicates hard exudates. Dot and blothemorrhages also are visible.

Table 1. Subdivisions and Characteristic Lesions ofDiabetic Retinopathy

Nonproliferative retinopathy

Microaneurysms

Hemorrhages

Hard exudates

Cotton-wool spots

Macular edema

Proliferative retinopathy

Neovascularization

HYPERTENSION

The funduscopic changes in the eye noted withhypertension were first described in 1898.12 Since thattime, little has changed in the terminology describingthese characteristic retinal abnormalities. These char-acteristic retinal changes included arteriolar narrow-ing, arteriovenous crossing changes, alterations of lightreflexes on arterioles, cotton-wool spots, micro-aneurysms, retinal hemorrhages, retinal edema, andblurred disc margins.13

The first and most widely used grading system forhypertensive retinopathy was proposed by Keith et al.14

The classification system consists of 4 grades as follows:

Grade I: mild narrowing of the retinal arterioles

Grade II: arteriovenous nicking (ie, venous com-pression at arteriovenous crossings) (Figure 5)

Grade III: cotton-wool spots, hemorrhages (Fig-ure 6), retinal edema

Grade IV: optic disc edema (Figure 7)

A newer more simplified grading system was recent-ly proposed and divides the features, according to

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www.turner-white.com Hospital Physician November 2003 17

Figure 4. The arrow indicates a cotton-wool spot.

Figure 5. Hypertensive retinopathy showing arteriovenousnicking (arrow). (Reprinted with permission from BradfordCA. Basic ophthalmology for medical students and primarycare residents. 7th ed. San Francisco: American Academy ofOphthalmology; 1999:135.)

Figure 6. The arrow indicates retinal hemorrhages. Hardexudates also are visible.

Figure 7. Malignant hypertension showing optic disc edema.Also seen are flame-shaped hemorrhage, hard exudates, arte-rial constriction, and cotton-wool spots. (Reprinted with per-mission from Bradford CA. Basic ophthalmology for medicalstudents and primary care residents. 7th ed. San Francisco:American Academy of Ophthalmology; 1999:135.)

prognosis, into 2 categories: nonmalignant and malig-nant hypertension.15 Nonmalignant findings includearteriolar narrowing and arteriovenous nicking; malig-nant findings consist of hemorrhages, hard exudates,cotton-wool spots, and optic disc edema. Hard exu-dates in the macula would suggest diabetic retinopathyversus hypertensive retinopathy in which the hard exu-dates would more likely appear in the peripheral reti-nal around a macroaneurysm. Optic disc edema canbe caused by other conditions (eg, increased intracra-nial pressure); however, the presence of cotton-woolspots is highly suggestive of malignant hypertension asthe etiology of disc edema.16,17 In the case of malignanthypertension, optic disc edema is caused by ischemicoptic neuropathy.16 Papilledema develops within daysto weeks of increased blood pressure and resolves with-in weeks to months following lowering of blood pres-sure.

Retinal vascular abnormalities, such as arteriolarnarrowing and arteriovenous nicking, are irreversiblelong-term markers of hypertension. These nonmalig-nant hypertensive retinal vascular changes persist longterm even after successful antihypertensive therapy.18

Retinal vascular abnormalities are useful risk indicatorsfor cerebrovascular disease and stroke.19

Early detection of malignant hypertension is essen-tial in reducing the likelihood of permanent visualdamage.20 Malignant hypertensive retinal changes suchas papilledema, cotton-wool spots, and hemorrhagesresolve if blood pressure is well controlled.18 Malignanthypertensive retinal changes are likely findings inpatients in hypertensive crisis, which is an abrupt eleva-tion in blood pressure with a systolic blood pressure ofgreater than 210 mm Hg and a diastolic blood pressureof more than 120 mm Hg.

Ischemic optic neuropathy is a common cause ofvisual loss. Hypertension is the most frequently report-ed underlying disease. Ischemic optic neuropathy is adirect complication of hypertension, which affects thesmall arterioles supplying the anterior part of the opticnerve. Patients with ischemic optic neuropathy fre-quently report blurred vision, and funduscopic exami-nation reveals optic disc edema.

CONCLUSION

Hypertension and diabetes are commonly encount-ered systemic diseases in primary care. A thorough eyeexamination can uncover retinal manifestations ofthese disease processes and thus prevent further dam-age leading to visual impairment. A basic understand-ing of these common retinal manifestations is essentialin primary care. HP

REFERENCES1. Ravin JG. Sesquicentennial of the ophthalmoscope.

Arch Ophthalmol 1999;117:16348.2. Bradford CA. Basic ophthalmology for medical students

and primary care residents. 7th ed. San Francisco: Amer-ican Academy of Ophthalmology; 1999.

3. Frith P, Gray R, Maclennan S, Ambler P. The eye in clini-cal practice. 2nd ed. Malden (MA): Blackwell Science;2001.

4. Seidel HM, Ball JW, Dains JE, Benedict GW. Mosbys guideto physical examination. 4th ed. St. Louis: Mosby; 1999.

5. Bickley LS. Bates guide to physical examination and his-tory taking. 7th ed. Philadelphia: Lippincott, Williams &Wilkins; 1999.

6. Aschner P. Current concepts of diabetes mellitus. IntOphthalmol Clin 1998;38:110.

7. Brechner RJ, Cowie CC, Howie LJ, et al. Ophthalmicexamination among adults with diagnosed diabetes mel-litus. JAMA 1993;270:17148.

8. Javitt JC, Aiello LP. Cost-effectiveness of detecting andtreating diabetic retinopathy. Ann Intern Med 1996;124(1 Pt 2):1649.

9. DAmico DJ. Diseases of the retina. N Engl J Med 1994;331:95106.

10. Feman SS. The natural history of the first clinically visiblefeatures of diabetic retinopathy. Trans Am OphthalmolSoc 1994;92:74573.

11. Doft BH, Kingsley LA, Orchard TJ, et al. The associationbetween long-term diabetic control and early retinopa-thy. Ophthalmology 1984;91:7639.

12. Walsh JB. Hypertensive retinopathy. Description, classifi-cation, and prognosis. Ophthalmology 1982;89:112731.

13. Wagener HP, Clay GE, Gipner JF. Classification of retinallesions in the presence of vascular hypertension. Oph-thalmol Trans Am Sci 1947;45:5773.

14. Keith NM, Wagener HP, Barker NW. Some differenttypes of essential hypertension: their course and progno-sis. Am J Med Sci 1939;197:33243.

15. Dodson PM, Lip GY, Eames SM, et al. Hypertensiveretinopathy: a review of existing classification systemsand a suggestion for a simplified grading system. J HumHypertens 1996;10:938.

16. Wall M. Optic disk edema with cotton-wool spot. SurvOphthalmol 1995;39:5028.

17. Lee AG, Beaver HA. Acute bilateral optic disk edemawith a macular star figure in a 12-year-old girl. Surv Op-thalmol 2002;47:429.

18. Bock KD. Regression of retinal vascular changes by anti-hypertensive therapy. Hypertension 1984;6(6 Pt 2):III15862.

19. Wong TY, Klein R, Couper DJ, et al. Retinal microvascu-lar abnormalities and incident stroke: the AtherosclerosisRisk in Communities Study. Lancet 2001;358:113440.

20. Browning AC, Mengher LS, Gregson RM, Amoaku WM.Visual outcome of malignant hypertension in youngpeople. Arch Dis Child 2001;85:4013.

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