NAION.54–57 These drugs increase the level of cyclic guanosine monophosphate in vascular smooth muscle cells which leads to vasodilation of arterioles and subsequent arterial hypotension. Because arterial hypotension, especially during sleep, is thought

to be associated with NAION, it is conceivable that these drugs could add to the risk of NAION.18,58

Hayreh states that diabetic patients should be counseled against their use for this reason. Similar concerns have been raised about nocturnal use of beta-blocker eyedrops for glaucoma.59

Posterior ischemic optic neuropathy is much less common than anterior ischemic optic neuropathy, comprising perhaps 2% of the cases of ischemic optic neuropathy.33 Affected patients tend to fall into three groups: perioperative cases, temporal arteritis-associated cases, and cases associated with nonarteritic systemic vascular disease.60 Because the condition is much rarer than anterior ischemic optic neuropathy, little data are available regarding the role of diabetes.60 The optic nerve appearance is normal at the time of the acute event. Optic disk pallor is seen approximately 6 weeks after the event.33 Central nervous system imaging is advisable to exclude a compressive lesion.

There is no proven effective therapy for NAION.61 Optic nerve sheath decompression is of no benefit and may be harmful.62 Other therapies

tried have included levodopa, hyperbaric oxygen, aspirin, and prednisone.30,63–66

13.4 Diabetic Papillopathy

Diabetic papillopathy is a clinical description of unilateral or bilateral optic disk edema with or without decreased visual function that improves with time in diabetics.67,68 Although no population-based studies exist to provide reliable prevalence data, an estimate of 0.4% of diabetics seen by ophthalmologists has been published.69 In the 42% of cases with bilateral involvement, the two eyes may be affected by simultaneously or sequentially involvement.69–71 As with NAION, the disk in diabetic papillopathy often has a

small cup and dilated radial peripapillary capillaries (Fig. 13.3).29,68,70 Although early reports suggested

that the condition usually occurs in patients under age 30 who have had longstanding type 1 diabetes

mellitus, more recent reports suggest that older

patients and patients with type 2 diabetes may actually comprise the majority of cases.67,70,72,73 A his-

tory of poor metabolic control is elicited in 50% of

patients, but the condition can occur in patients with good glycemic control and in pregnancy.67,68,73–75

The optic disk edema does not correlate with the degree of diabetic retinopathy. It usually resolves within 3–6 months, although it can persist for 1

year or more, and is not followed by dramatic optic atrophy, although mild pallor may be seen.67,68,71,76

Although diabetic retinopathy can be mild in affected eyes, accelerated retinopathy progression

to the point of proliferative disease occurs in 17%, thus close follow-up is warranted.69,73,77 Macular

edema and significant capillary nonperfusion are frequently present in affected eyes.70 Care must be taken to distinguish the macular edema associated with diabetic papillopathy from concomitant diabetic macular edema. In the former, the edema resolves spontaneously and no treatment is necessary.78 In the latter, focal/grid laser is of proven benefit.79 Visual field examinations reveal blind spot enlargement alone or no abnormality in

approximately equal proportions; occasionally arcuate or central scotomata are seen.68–70,73 Although

visual acuity is usually unaffected after resolution of edema, a decrease may be seen in approximately 8% of patients.73 Relative afferent pupillary defects are absent or rare and spontaneous venous pulsations may be seen.68 Cerebrospinal fluid pressure is normal in such cases, as is computed tomography of the brain.67–69 Recurrence of diabetic papillopathy is rare or unreported once the initial episode has resolved.68 Because the appearance of the optic disk is indistinguishable from the papilledema arising from increased intracranial pressure or hypertension, these latter conditions need to be excluded

before making the diagnosis of diabetic papillopathy.68,71,75,77

Some authors consider diabetic papillopathy to be incipient NAION in a patient with diabetes mel-

litus and not a distinct entity, although others disagree.30,67,68,70,71,80 Incipient NAION in patients

with diabetes can be accompanied by telangiectatic disk vessels easily confused with disk neovascularization.53 A distinction needs to be made, because

panretinal photocoagulation is needed for the one but not the other.30,53 The distinction can be made

Fig. 13.3 (a) Normal optic nerve head appearance of the left eye of a 30-year-old woman with type 1 diabetes of 27 years duration and poor glycemic control before the development of diabetic papillopathy (see Fig. 13.3b). Mild nonproliferative diabetic retinopathy was present and the visual acuity was 20/20. The optic nerve head cup is small. (b) Appearance

of the left optic nerve head of the patient shown in Fig. 13.3a when diabetic papillopathy developed. The visual acuity was 20/30. Prominent dilation of capillaries on the superficial optic nerve head is seen. The patient had a normal opening pressure on lumbar puncture

by assessing the degree of midperipheral capillary nonperfusion of the retina that is commonly present with disk neovascularization, and not characteristically present, although possibly present, in diabetic papillopathy. Another distinguishing characteristic is the location of the vessels. Disk neovascularization is found in the preretinal space, whereas the dilated capillaries of diabetic papillopathy are present within the plane of the retina.70 The leakage of dye from the vessels on fluorescein angiography is not a useful test for distinguishing the two, as it occurs in both.80 The late frames of the fluorescein angiogram can be helpful, however. The retinal arteries and veins of the disk are dark against the hyperfluorescent disk substance in the case of diabetic papillopathy. In contrast, in the case of disk neovascularization the fluorescein in front of the disk obscures the underlying arteries and veins of the disk.74

Although lumbar punctures in case reports have uniformly shown normal opening pressures, some have speculated that a mildly elevated cerebrospinal fluid pressure may contribute to the condition. Few patients have been studied with serial lumbar punctures to investigate this possibility.76 There is no known treatment for diabetic papillopathy, although excellent glycemic and blood pressure

control are recommended, as for all patients with

diabetes.69,71,75,81

13.5Disk Edema Associated with Vitreous Traction

Vitreopapillary traction associated in a patient with diabetic retinopathy can rarely be the cause of optic disk edema. With spontaneous posterior vitreous detachment, the edema resolves.82

13.6Superior Segmental Optic Hypoplasia (Topless Optic Disk Syndrome)

Superior segmental optic hypoplasia is a congenital, stable optic disk anomaly often but not

always occurring in the offspring of mothers with type 1 diabetes mellitus.83–85,86 Although

affected patients have been predominantly female in some case series, the gender imbalance did not reach statistical significance in a popu- lation-based study.83,87 Bilateral disk involvement occurs in 22–67% of cases.86,87 Familial clustering has been reported suggesting a genetic component to the disorder.88,89 Short gestation time, low birth weight, and poor maternal diabetic control seem to be risk

factors.83 Patients typically have good visual acuity, but inferior visual field defects are pre-

sent and the optic nerves and sometimes chiasm are small on MRI scanning.86,87

Fundus findings include a superior disk entrance

of the central retinal artery, superior disk pallor, and a superior scleral halo (Fig. 13.4).83,84,90 Optical

coherence tomography shows retinal nerve fiber layer thinning superiorly.84 The appearance of the optic disk can be subtly abnormal and can be confused with the disk in normal tension glaucoma, although in the latter disorder the neural rim thinning is usually located inferiorly. The reported prevalence has been from 0.08 to 0.3%, approximately

one-tenth the prevalence of normal tension glaucoma.84,87

13.7 Wolfram Syndrome

Wolfram syndrome is an autosomal recessive, progressive neurodegenerative syndrome consisting of insulin-dependent diabetes mellitus, diabetes insipidus, sensorineural hearing loss, ataxia, peripheral

neuropathy, urinary tract atrophy, psychiatric illness, and progressive optic nerve atrophy (Fig. 13.5).91,98

It is also called DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness).92 Diabetes mellitus and optic atrophy are the major features, present in 98–99% of cases, whereas diabetes insipidus and deafness are minor features, occurring in 32–35% and 12% of cases, respectively.93 Its manifestations occur in stages

Fig. 13.4 Characteristic features of superior segmental optic hypoplasia are illustrated. (a) The central retinal artery enters the optic disk superiorly (arrow). There is a superior peripapillary scleral halo (arrowheads). (b) Red free fundus photograph shows thinning of the superior

nerve fiber layer (arrows). (c) The optical coherence tomography shows retinal nerve fiber layer thinning in the superonasal quadrant. (d) Humphrey 24-2 visual field testing shows an inferior arcuate scotoma. Reprinted with permission from Han.84

Fig. 13.5 Optic disk atrophy in an 8-year-old boy with

Wolfram syndrome. Reprinted with permission from Wake98

with diabetes mellitus and optic atrophy by age 10; diabetes insipidus and deafness by age 20; renal tract abnormalities by age 30; cerebellar ataxia, myoclonus, and psychiatric illness by age 40; and death from central respiratory failure usually by age 50.92 Estimates of incidence range from 1:100,000 to 1:770,000 in South America and the United Kingdom, respectively.94 MRI studies of the brains of affected persons can show cerebellar and pontine atrophy, shrinkage of the optic nerves and chiasm, and foci of high signal on PDand T2weighted images in the substantia nigra.93,95 Neuropathology shows atrophy of the olfactory tracts, optic nerves and chiasm, loss of neurons in the lateral geniculate body, atrophy of the superior colliculus, cochlear nerve fiber loss, olivopontocerebellar atrophy, and demyelination of pyramidal tracts.91

The responsible gene, WFS1 on the short arm of chromosome 4, has no known function as yet, but

more than 50 mutations have already been described in affected individuals.92,94,96 Multiple

deletions of mitochondrial DNA have also been associated with the condition.97 There is no known treatment for the disease. Management consists of treating the complications of the genetic defect as they arise over a lifetime.94

13.8 Summary of Key Points

The vascular supply of the anterior optic nerve is primarily derived from the short posterior ciliary arteries. The vessels show autoregulation by locally released molecules such as nitric oxide, endothelin, prostaglandins, and members of the renin–angiotensin pathway.

Blood pressure and intraocular pressure influence anterior optic nerve perfusion pressure. Diurnal variation in blood pressure is an important variable to consider in the use of vasoactive medications.

Optic disk cup size is a risk factor for nonarteritic anterior ischemic optic neuropathy (NAION). The mechanism seems to be ischemia ! axoplasmic flow stasis and axonal swelling! crowding of axons as they exit the eye!compression of optic disk capillaries!worse ischemia (a vicious cycle).

The peripapillary nerve fiber layer thickness is increasingly reduced in diabetes as retinopathy severity worsens.

Evidence exists for subclinical optic disk neuroretinal rim edema in diabetic eyes.

Diabetes is a risk factor for NAION and is associated with more florid disk capillary dilation and peripapillary splinter hemorrhage, a longer course until edema resolution, and a shorter time until fellow eye involvement with NAION than in nondiabetic eyes with NAION. Other treatable risk factors include sleep apnea and nocturnal use of anti-hypertensive medications. Male patients at risk for NAION should probably avoid the use of phosphodiesterase-5 inhibitors to treat erectile dysfunction.

Diabetic papillopathy, a syndrome of unilateral or bilateral disk edema with or without visual dysfunction that spontaneous resolves, is controversially related to NAION.

Superior segmental optic hypoplasia is a rare congenital disk anomaly associated in many cases with maternal type 1 diabetes mellitus. It can masquerade as normal tension glaucoma, but unlike the latter, is nonprogressive.

Wolfram syndrome is a rare neurodegenerative disorder caused by a mutation in the WFS1 gene