Optic Nerve Disease in Diabetes Mellitus

13.1Relevant Normal Optic Nerve Anatomy and Physiology

The vascular supply of the optic nerve depends on the stratum of the optic nerve head under consideration. The optic nerve head is divided into four strata

– superficial nerve fiber layer, prelaminar layer, laminar layer, and retrolaminar layer. Fine retinal arterioles arising in the peripapillary retina and derived from the central retinal artery supply the superficial nerve fiber layer of the optic nerve; there is no posterior ciliary contribution.1The prelaminar and laminar optic nerve derive their blood supply primarily from the paraoptic short posterior ciliary arteries and the circumferential vessels of the circle of Zinn-Haller (Fig. 13.1).2–5 The circle of Zinn-Haller, where it exists, is an intermediary between the posterior ciliary arteries and the anterior optic nerve small vessels.1,6 There may be smaller and inconsistent

contributions from peripapillary choroidal arteries.1,2,6,7 Although the circle of Zinn-Haller is

present in the peripapillary sclera in most eyes studied by plastic cast studies in cadaver eyes, there is some controversy about whether the circle is functional and whether it serves as an intermediary between the short posterior ciliary arteries and the optic disk blood supply.1,8 In vivo, the perfusion of the circle of Zinn-Haller can only be seen in highly myopic eyes with peripapillary crescents by using ICG angiography.9 In such eyes, the circle of Zinn-

D.J. Browning (*)

Charlotte Eye Ear Nose & Throat Associates, Charlotte, NC 28210, USA

e-mail: dbrowning@ceenta.com

Haller has been found to be incomplete, but one cannot generalize to the case of normal eyes. The mesh of capillaries in the anterior optic nerve has spacing of 30–50 mm to 50–85 mm and connects with the capillary mesh of the laminar portion of the optic

disk and the overlying superficial nerve fiber layer.1,2,10 The capillaries themselves have a luminal

diameter of 7–10 mm.2 Electron microscopy shows tight junctions between capillary endothelial cells of the optic nerve, thus a blood–optic nerve barrier exists in analogy to the blood–retina barrier.11,12 The retrolaminar optic nerve head is supplied both by the short posterior ciliary arteries via branches to the circle of Zinn-Haller and thence to pial arteries and by branches of the central retinal artery.13

The intravascular pressure of the short posterior ciliary artery branches to the anterior optic nerve has been deduced to be somewhat lower than the intravascular pressure of branches of the central retinal artery based on fluorescein angiograms of primates performed with elevated, controlled intraocular pressure in an experimental model suggesting vulnerability of the optic nerve head should perfusion pressure fall.3

The optic nerve shares the property of autoregulation with the retina.12,14–16 Systemic controls on

optic nerve blood flow are absent or minor, but local factors mediated by nitric oxide, endothelin, prostaglandins, and the renin–angiotensin system are important.17 The ocular perfusion pressure (OPP) is defined as follows:

OPP = mean rterial blood pressure – intraocular pressure

=[diastolic blood pressure + 1/3 (systolic

blood pressure – diastolic blood pressure)]

– intraocular pressure 14,18

In most, but not all, humans, the optic nerve vascular response to an increase in perfusion pressure of up to 45 mm Hg is vasoconstriction such that optic nerve head blood flow tends to remain constant. Likewise, with a fall in perfusion pressure by raising intraocular pressure, the optic disk arterioles tend to dilate and protect optic disk oxygen tension.12 Some persons seem to have a reduced optic nerve autoregulatory capacity and may be more susceptible to ischemia of the optic nerve. Although both arterial blood pressure and intraocular pressure affect the ocular perfusion pressure, it is not known if changes induced by the two factors produce equivalent responses.14

13.2The Effect of Diabetes on the Optic Nerve

The retinal nerve fiber layer thickness is reduced in diabetes mellitus compared to control eyes with increasing atrophy as retinopathy severity

increases. Thus diabetes can be a source of overestimation of glaucomatous optic neuropathy when scanning laser polarimetry is used to monitor progression of glaucomatous optic atrophy.19

The neuroretinal rim area of the optic nerve has been studied longitudinally in a subset of photographs taken as part of the Wisconsin Study of Diabetic Retinopathy.20 In younger onset and older onset diabetics, the neuroretinal rim area increased over a 4-year period. In addition, the neuroretinal rim area was larger in eyes with more severe retinopathy at baseline. It is possible that diabetes is associated with subclinical optic disk swelling in general.

Although rare, optociliary shunt vessels can arise de novo in diabetic retinopathy, perhaps signifying a relative venous obstruction at the lamina cribrosa. The more common causes of optociliary shunt vessels are spheno-orbital meningiomas, central retinal vein occlusions, primary open angle glaucoma, papilledema, optic nerve glioma, optic disk drusen, arachnoid cyst of the

optic nerve, phakomatoses, and rarely congenital abnormality.21

13.3Nonarteritic Anterior Ischemic Optic Neuropathy and Diabetes

Nonarteritic anterior ischemic optic neuropathy (NAION) is generally considered to occur as a response to hypoperfusion of the branches of the

posterior ciliary arteries that supply the optic disk.22–25 An alternative hypothesis – that the pri-

mary disorder is relative central venous occlusion – has been advanced but not embraced.26 The annual

incidence of NAION is 2.3–10.3 per 100,000 persons.24,25 Although more common in the elderly

with the median age of affected patients being 62 years, it can strike the young (range 12–92 years).27 Visual loss is most frequently noted upon awakening from sleep suggesting that nocturnal hypotension may have a role in the condition.28 Hypoxia induces axoplasmic flow stasis, neural swelling, and dilated capillaries on the surface of the disk with peripapillary splinter hemorrhages more prominent

in patients with diabetes than in those without (Fig. 13.2).29,30 Because the space through which

the optic nerve passes is typically restricted as reflected in a small optic disk cup, the axonal swelling is thought to compress the capillaries further, in turn exacerbating ischemia and producing a vicious spiral ending in tissue infarction.30–32 Diabetes mellitus is a risk factor for NAION, and others include hypertension, nocturnal or post-surgical

hypotension, older age, smoking, sleep apnea, and anemia.23,33–42 Cataract surgery may be a minor

risk factor.43 The role of thrombophilic factors has been inconsistent. Although thrombophilic risk factors have been absent in most studies, one study reported elevated levels of lipoprotein (a), von Willebrand antigen, factor V Leiden, cholesterol, and fibrinogen in patients with NAION.44–46

Central scotomata are present in 55.3% and 36.2% of eyes with the I-2e and V-4e targets, respectively.47 Inferonasal sector loss is the most common sectoral defect (22.4%).47 An inferior altitudinal field defect is seen in 8.0% of eyes.47 Many other visual field defects can be seen and in 6.4% of eyes no field defect is present.47 The sector

of optic disk edema and the location of the visual field defects correlate early in the condition.30 As the edema resolves, however, the correlation vanishes.25 At a later stage, the correlation of sectoral optic pallor and the observed visual field defects is also poor.30 A relative afferent pupillary defect is usually present.33

Before visual dysfunction occurs, there may be asymptomatic optic disk edema, which has been

termed incipient nonarteritic anterior ischemic optic neuropathy (Fig. 13.2).22,48,49 Twenty five to

31% of cases of incipient NAION resolve with the

rest progressing to NAION and some visual loss involving acuity or field or both.22,50

Previous fellow eye involvement at baseline is seen in 21.1% of patients and new fellow eye involvement occurs in 14.7% of patients over 5 years of follow-up with half the cases occurring in the first year after first eye involvement.23 Presence of diabetes mellitus

increases the incidence of fellow eye involvement.23 Recurrences in the same eye are uncommon.51,52

NAION in patients with diabetes has some differences compared to the condition in nondiabetics. Diabetic patients with NAION have a higher prevalence of hypertension, ischemic heart disease, transient ischemic attacks, and second eye involve-

ment than patients who have NAION without diabetes.23,53 Time to resolution of disk edema is longer

in patients with diabetes than in patients without diabetes.30,53 Median time to second eye involvement is shorter in patients with diabetes than in patients without diabetes.53 In some respects, diabetic and nondiabetic patients are similar. The fluorescein angiographic findings are the same. The optic disk shows fluorescein leakage of swollen sectors in both groups of patients.30,53 Both groups of patients have small cup-to-disk ratios. At 6 months after diagnosis, the visual acuity and visual field outcomes are similar in diabetic and nondiabetic groups.53

Subsequent optic disk pallor after the acute

hyperemia of NAION occurs approximately 6–12 weeks later.30,33 Atrophic cupping of the optic nerve

after NAION is not seen, in contrast to arteritic ION, where subsequent optic cupping can be part of the clinical picture.33

Although controversial, some have linked the use of phosphodiesterase-5 inhibitors for the treatment of erectile dysfunction and the development of

Fig. 13.2 Example of incipient nonarteritic ischemic optic neuropathy. The patient was a 65-year-old man with type 2, insulin-requiring diabetes mellitus, hypertension, and sleep apnea. He had had uneventful cataract surgery in the right eye 8 months earlier and in the left eye 3 months earlier. He complained of acute onset of painless, blurred vision of the left eye for 3 weeks and had no complaints with regard to the right eye. Best corrected visual acuity was 20/20 in each

eye. Both eyes had optic disk edema, more prominent on the left than the right (a and b); on the right only the superior pole of the nerve was involved. Fluorescein angiography showed late disk hyperfluorescence bilaterally, more prominent on the left than the right (c and d). The visual field was normal on the right (mean defect –1.94 db) and showed some patchy superior scotomata on the left (mean defect –3.42 db) (e and f)