**9. Acquired optic disc disorders**

#### **9.1. Papilledema**

Papilledema is the bilateral disc swelling secondary to increased intracranial pressure. Although bilateral it may be asymmetrical. It can be caused by space occupying lesions in the cavity of the skull, idiopathic intracranial hypertension, obstruction of the ventricles, impaired cerebrospinal fluid adsorption by the arachnoid villi, severe systemic hypertension, cerebral venous thrombosis, diffuse cerebral oedema following trauma.

Differential diagnosis includes: malignant hypertension, bilateral optic neuritis with optic nerve head involvement (papillitis), bilateral anterior ischemic optic neuropathy, diabetic papillopathy, Leber's hereditary optic neuropathy, pseudopapilledema (optic disc drusen, hypermetropia), and toxic optic neuropathy.

Optical coherence tomography is helpful in diagnosing early papilledema. Vartin et al [78] found that the peripapillary total retinal thickness rather than the conventionally calculated RNFL thickness as measured with spectral domain OCT differentiated early papilledema from normal subjects. Peripapillary total retinal thickness as a diagnostic tool for subtle papilledema was also reported by Skau et al [79]. OCT is useful in the follow up of patients with papilledema. Rebolleda et al [80] followed up patients with papilledema for 12 months following presenta‐ tion and found that RNFL thickness decreased with time and visual field defects improved. Kupersmith et al [81] investigated different causes of optic disc swelling [papilledema, nonarteritic anterior ischemic optic neuropathy (NA-AION ) and optic neuritis] with OCT and scanning laser polarimetry (SLP). Retinal nerve fiber thickness by OCT was increased in papilledema and NA-AION compared to eyes suffering from optic neuritis. This is due to greater disc edema in eyes with papilledema and NA-AION. SLP showed increased RNFL thickness in papilledema and optic neuritis. The authors concluded that OCT reveals increased retinal thickness due to axonal swelling but SLP shows the true damage of the axons.

Two studies investigated the morphology of the retinal pigment epithelium/Bruch's mem‐ brane (RPE/BM) complex and concluded that papilledema causes an inward (towards the vitreous cavity) bowing of the PRE/BM complex as opposed to patients with AION and optic neuritis [82,83]. The authors speculate that the increased pressure in the cerebrospinal fluid (CSF) caused the forward bowing of the RPE/BM complex. In the other types of disc swelling (AION, optic neuritis) pathophysiologically there is no high pressure of the CSF.

### **9.2. Optic Neuritis (ON) (fig 19)**

Optic neuritis is the inflammatory process of the optic nerve. Anatomically it can affect the optic nerve head (papillitis), only the posterior part of the nerve (retrobulbar neuritis) or both.

Differential diagnosis includes: anterior ischemic optic neuropathy, compressive lesions of the optic nerve, Leber's hereditary optic neuropathy, central retinal vein occlusion, infiltration of the optic nerve head (sarcoidosis, tuberculosis, syphilis, leukemia)

Optical coherence tomography has been used in the diagnosis and follow up of patients with isolated optic neuritis or optic neuritis in clinically diagnosed multiple sclerosis (MS). It was found that as expected the patients with previous history of ON had thinner RNFL than normal subjects [84,85]. OCT can also demonstrate structural damage more accurately than standard automated perimetry. Noval et al reported that OCT can detect subtle RNFL changes in the presence of normal visual fields [86]. Interestingly Pro et al described RNFL thickening in the acute phase of ON even in patients without disc swelling [87]. OCT has been used in the follow up of patients with ON over time. Costello et al reported that the RNFL loss is more profound between the third and sixth month after the episode of ON [88]. The earliest damage in the RNFL is evident 2 months after clinical presentation and the RNFL damage halts 7 months after the episode of ON [89,90]. In patients suffering from multiple sclerosis, eyes unaffected by ON demonstrate lower RNFL thickness compared to normal subjects [91-95]. OCT findings have also been linked to visual function. Average RNFL thickness of less than 75µm predicted persistent visual dysfunction (90) and for every 1 line of reduced contrast sensitivity the RNFL thickness decreased by 4µm (91).

**9.3. Ischaemic optic neuropathy**

Anatomically is classified as anterior and posterior and aetiologically as non-arteritic and arteritic. Predisposing factors for the non-arteritic anterior ischaemic optic neuropathy (NA-AION) is hypertension, diabetes mellitus, hyperlipidemia, sleep apnea, cataract surgery, erectile dysfunction, small crowded optic disc and long standing papilledema, while arteritic anterior ischaemic optic neuropathy (A-AION) is caused by giant cell arteritis. Posterior ischaemic optic neuropathy involves the retrolaminal part of the optic nerve. It can follow a heart or spine operation or be caused by giant cell arteritis or present as the posterior equivalent

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Optical coherence tomography in the acute stages of AION shows diffuse thickening of the RNFL which turns into thinning as the disease becomes chronic (100,101) (fig. 20,21,22). Contreras et al (102) found that the superior RNFL quadrant was more affected and that for every 1µm of nerve fiber thickness loss there was 1 dB decrease of mean deviation in standard automated perimetry. OCT analysis of the RNFL showed RNFL thinning compared to healthy controls and the area of retinal axon loss correlated well with visual field defects (102-105).

Research has shown that that AION and glaucoma affect the optic nerve differently. RNFL thickness in glaucoma and NA-AION eyes is not statistically different but it is markedly thinner compared to normal eyes (61,107). However when adjusting for mean deviation (MD) of visual fields RNFL was thicker in eyes with A-AION and NA-AION compared to open angle

Macular thickness also correlated with visual field loss in eyes with NA-AION (106).

of non-arteritic AION. Differential diagnosis is as in optic neuritis.

**Figure 19.** Swollen RNFL in a patient with papillitis secondary to multiple sclerosis.

Secondary progressive MS was associated with greater RNFL decrease in both affected and unaffected by ON eyes (90, 92). Decreased RNFL thickness was also inversely associated with disease severity (the lower the RNFL thickness the more serious the disease) (95-97). Retinal nerve fiber thickness on OCT could not predict the risk of MS (96). In one study comparing the structural damage after optic neuritis it was found that only the modalities that measure RNFL thickness (OCT, GDx) were affected compared to disease free participants but the analysis of the optic disc with the HRT 3 was not statistically different compared to normal control group (99).

**Figure 19.** Swollen RNFL in a patient with papillitis secondary to multiple sclerosis.

#### **9.3. Ischaemic optic neuropathy**

greater disc edema in eyes with papilledema and NA-AION. SLP showed increased RNFL thickness in papilledema and optic neuritis. The authors concluded that OCT reveals increased

Two studies investigated the morphology of the retinal pigment epithelium/Bruch's mem‐ brane (RPE/BM) complex and concluded that papilledema causes an inward (towards the vitreous cavity) bowing of the PRE/BM complex as opposed to patients with AION and optic neuritis [82,83]. The authors speculate that the increased pressure in the cerebrospinal fluid (CSF) caused the forward bowing of the RPE/BM complex. In the other types of disc swelling

Optic neuritis is the inflammatory process of the optic nerve. Anatomically it can affect the optic nerve head (papillitis), only the posterior part of the nerve (retrobulbar neuritis) or both.

Differential diagnosis includes: anterior ischemic optic neuropathy, compressive lesions of the optic nerve, Leber's hereditary optic neuropathy, central retinal vein occlusion, infiltration of

Optical coherence tomography has been used in the diagnosis and follow up of patients with isolated optic neuritis or optic neuritis in clinically diagnosed multiple sclerosis (MS). It was found that as expected the patients with previous history of ON had thinner RNFL than normal subjects [84,85]. OCT can also demonstrate structural damage more accurately than standard automated perimetry. Noval et al reported that OCT can detect subtle RNFL changes in the presence of normal visual fields [86]. Interestingly Pro et al described RNFL thickening in the acute phase of ON even in patients without disc swelling [87]. OCT has been used in the follow up of patients with ON over time. Costello et al reported that the RNFL loss is more profound between the third and sixth month after the episode of ON [88]. The earliest damage in the RNFL is evident 2 months after clinical presentation and the RNFL damage halts 7 months after the episode of ON [89,90]. In patients suffering from multiple sclerosis, eyes unaffected by ON demonstrate lower RNFL thickness compared to normal subjects [91-95]. OCT findings have also been linked to visual function. Average RNFL thickness of less than 75µm predicted persistent visual dysfunction (90) and for every 1 line of reduced contrast sensitivity the RNFL

Secondary progressive MS was associated with greater RNFL decrease in both affected and unaffected by ON eyes (90, 92). Decreased RNFL thickness was also inversely associated with disease severity (the lower the RNFL thickness the more serious the disease) (95-97). Retinal nerve fiber thickness on OCT could not predict the risk of MS (96). In one study comparing the structural damage after optic neuritis it was found that only the modalities that measure RNFL thickness (OCT, GDx) were affected compared to disease free participants but the analysis of the optic disc with the HRT 3 was not statistically different compared to normal

retinal thickness due to axonal swelling but SLP shows the true damage of the axons.

(AION, optic neuritis) pathophysiologically there is no high pressure of the CSF.

the optic nerve head (sarcoidosis, tuberculosis, syphilis, leukemia)

**9.2. Optic Neuritis (ON) (fig 19)**

314 Glaucoma - Basic and Clinical Aspects

thickness decreased by 4µm (91).

control group (99).

Anatomically is classified as anterior and posterior and aetiologically as non-arteritic and arteritic. Predisposing factors for the non-arteritic anterior ischaemic optic neuropathy (NA-AION) is hypertension, diabetes mellitus, hyperlipidemia, sleep apnea, cataract surgery, erectile dysfunction, small crowded optic disc and long standing papilledema, while arteritic anterior ischaemic optic neuropathy (A-AION) is caused by giant cell arteritis. Posterior ischaemic optic neuropathy involves the retrolaminal part of the optic nerve. It can follow a heart or spine operation or be caused by giant cell arteritis or present as the posterior equivalent of non-arteritic AION. Differential diagnosis is as in optic neuritis.

Optical coherence tomography in the acute stages of AION shows diffuse thickening of the RNFL which turns into thinning as the disease becomes chronic (100,101) (fig. 20,21,22). Contreras et al (102) found that the superior RNFL quadrant was more affected and that for every 1µm of nerve fiber thickness loss there was 1 dB decrease of mean deviation in standard automated perimetry. OCT analysis of the RNFL showed RNFL thinning compared to healthy controls and the area of retinal axon loss correlated well with visual field defects (102-105). Macular thickness also correlated with visual field loss in eyes with NA-AION (106).

Research has shown that that AION and glaucoma affect the optic nerve differently. RNFL thickness in glaucoma and NA-AION eyes is not statistically different but it is markedly thinner compared to normal eyes (61,107). However when adjusting for mean deviation (MD) of visual fields RNFL was thicker in eyes with A-AION and NA-AION compared to open angle

**Figure 20.** RNFL swelling in a patient with NA-AION 4 weeks following presentation.

glaucoma eyes. For the same level of MD, open angle glaucoma eyes had larger cup area, smaller rim area, larger cup/disc ratio, larger cup volume, smaller rim volume, and greater cup depth. When comparing the two types of AION, the non-arteritic type had smaller cup area, a larger rim area, and a smaller cup/disc ratio (61). In order to explain the discrepancy in the morphology of the optic nerve damage between both types of AION and glaucoma the authors suggest that glaucoma affects laminar connective tissue more than the prelaminar structures (as opposed to AION) and this causes the development of larger and deeper cups in glaucoma. The loss of laminar connective tissue leads in turn to retrodisplacement and thinning of the lamina cribrosa which causes the larger cup size in glaucoma. Both glaucoma and AION cause retinal gagglion cell loss but AION does not affect the laminar tissues.

**Figure 21.** Same patient as in fig 20 3 months after initial presentation of NA-AION. Swelling of the RHFL has subsided

Recognizing a Glaucomatous Optic Disc http://dx.doi.org/10.5772/55157 317

**Figure 22.** Fellow eye of the same patient as in fig 10 showing a crowded disc.

and atrophy has begun to set in.

#### **9.4. Leber's Hereditary Optic Neuropathy (LHON)**

LHON is a rare mitochondrial disorder that affects males and is associated with mutations of the maternal mitochondrial DNA. It presents with acute loss of vision between the ages 10 – 60 but most often in the age range 15-35. Early signs are optic disc hyperaemia and nerve fiber swelling. In the later stages optic atrophy dominates the clinical picture. Differential diagnosis is as in papilledema.

OCT demonstrated statistically significant increase of the RNFL thickness (mean, superior, inferior, nasal) in the early stage of the disease (6-8 weeks after initial presentation). Nine months after onset there is a decrease in RNFL thickness in all but nasal quadrants (108,109).

**Figure 21.** Same patient as in fig 20 3 months after initial presentation of NA-AION. Swelling of the RHFL has subsided and atrophy has begun to set in.

**Figure 22.** Fellow eye of the same patient as in fig 10 showing a crowded disc.

glaucoma eyes. For the same level of MD, open angle glaucoma eyes had larger cup area, smaller rim area, larger cup/disc ratio, larger cup volume, smaller rim volume, and greater cup depth. When comparing the two types of AION, the non-arteritic type had smaller cup area, a larger rim area, and a smaller cup/disc ratio (61). In order to explain the discrepancy in the morphology of the optic nerve damage between both types of AION and glaucoma the authors suggest that glaucoma affects laminar connective tissue more than the prelaminar structures (as opposed to AION) and this causes the development of larger and deeper cups in glaucoma. The loss of laminar connective tissue leads in turn to retrodisplacement and thinning of the lamina cribrosa which causes the larger cup size in glaucoma. Both glaucoma and AION cause retinal gagglion cell loss but AION does not affect the laminar tissues.

**Figure 20.** RNFL swelling in a patient with NA-AION 4 weeks following presentation.

LHON is a rare mitochondrial disorder that affects males and is associated with mutations of the maternal mitochondrial DNA. It presents with acute loss of vision between the ages 10 – 60 but most often in the age range 15-35. Early signs are optic disc hyperaemia and nerve fiber swelling. In the later stages optic atrophy dominates the clinical picture. Differential diagnosis

OCT demonstrated statistically significant increase of the RNFL thickness (mean, superior, inferior, nasal) in the early stage of the disease (6-8 weeks after initial presentation). Nine months after onset there is a decrease in RNFL thickness in all but nasal quadrants (108,109).

**9.4. Leber's Hereditary Optic Neuropathy (LHON)**

is as in papilledema.

316 Glaucoma - Basic and Clinical Aspects

Unaffected male carriers had higher RNFL thickness in the temporal and inferior quadrants which was more pronounced in those with the 11778 mutation. Unaffected female carriers had a RNFL thickness increase in the temporal quadrant more pronounced in those with the 11778 mutation (110). Patients with the 11778 mutation tend to have increased RNFL thickness in the early stages of the disease and decreased thickness in the later stages compared to those with the 14484 mutation (111).

optic disc analysis. Clinical examination is of utmost importance before reaching the diagnosis

The authors have no proprietary interest in any of the products mentioned in the manuscript

Eye Department, University Hospital of Alexandroupolis, Alexandroupolis, Greece

[1] Piette, S. D, & Sergott, R. C. Pathological optic-disc cupping.Curr Opin Ophthalmol.

[2] Airaksinen, P. J, Drance, S. M, Douglas, G. R, Mawson, D. K, & Nieminen, H. Diffuse and localized nerve fiber loss in glaucoma. Am J Ophthalmol. (1984). Nov;, 98(5),

[3] Airaksinen, P. J, & Nieminen, H. Retinal nerve fiber layer photography in glaucoma.

[4] Badalà, F, Nouri-mahdavi, K, Raoof, D. A, Leeprechanon, N, Law, S. K, & Caprioli, J. Optic disk and nerve fiber layer imaging to detect glaucoma. Am J Ophthalmol. (2007).

[5] Zangwill, L. M, Williams, J, Berry, C. C, Knauer, S, & Weinreb, R. N. A comparison of optical coherence tomography and retinal nerve fiber layer photography for detection of nerve fiber layer damage in glaucoma. Ophthalmology. (2000). Jul;, 107(7), 1309-15.

[6] Deleón-ortega, J. E, & Arthur, S. N. McGwin G Jr, Xie A, Monheit BE, Girkin CA. Discrimination between glaucomatous and nonglaucomatous eyes using quantitative imaging devices and subjective optic nerve head assessment. Invest Ophthalmol Vis

[7] Greaney, M. J, Hoffman, D. C, Garway-heath, D. F, Nakla, M, Coleman, A. L, & Caprioli, J. Comparison of optic nerve imaging methods to distinguish normal eyes from those

with glaucoma. Invest Ophthalmol Vis Sci. (2002). Jan;, 43(1), 140-5.

and Georgios Labiris

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of glaucomatous optic neuropathy

Vassilis Kozobolis, Aristeidis Konstantinidis\*

(2006). Feb;, 17(1), 1-6.

Nov;, 144(5), 724-32.

Ophthalmolog (1985). , 92, 877-879.

Sci. (2006). Aug;, 47(8), 3374-80.

\*Address all correspondence to: aristeidiskon@hotmail.com

**Acknowledgements**

**Author details**

**References**

566-71.

#### **9.5. Optic atrophy**

Optic atrophy is classified aetiologically as:

Primary (not associated with previous optic disc swelling. Most common causes are compres‐ sive lesions of the optic pathways up to the lateral geniculate bodies, hereditary disorders and multiple sclerosis).

Secondary (following longstanding swelling of the optic nerve head (papilledema, AION, papillitis)

Consecutive (following retinal diseases with widespread destruction of the retina such as retinitis pigmentosa, central retinal artery occlusion, vasculitis)

The new devices for the analysis of RNFL have been employed for the differential diagnosis of those types of optic atrophy in which the features of glaucomatous versus non-glaucoma‐ tous optic nerve damage are not clear. Autosomal dominant optic atrophy (ADOA, Kjer's optic neuropathy) is a rare hereditary disorder [it affects 1:35,000 people in the general population (112)] that can be misdiagnosed for normal tension glaucoma (113) and in this cases OCT provide useful information in order to reach the correct diagnosis. Several reports have shown that eyes with ADOA have reduced mean RNFL thickness and the quadrant most commonly affected being the temporal one (114-117). In contrast the glaucomatous process typically affects the inferior and superior sectors (118). There is also a reduction in macular thickness in patients with ADOA (119). Barboni et al (120) reported that the optic nerve heads in patients with ADOA have smaller size compared to normal controls.

Chiasmal compressive lesions produce a characteristic bitemporal hemianopia which is due to the preservation of the uncrossed fibers that originate from the temporal retina and enter the optic disc with the superior and inferior arcuate bands. The main damage therefore occurs in the nasal and temporal sectors of the disc and causes a characteristic ophthalmoscopic appearance named band atrophy. OCT has shown that not only the nasal and temporal sectors of the RNFL are affected but also the superior and inferior ones (121-123). OCT analysis of the optic nerve head could depict better than the Heidelberg Retina Tomograph the rim loss and subsequently the increased cup area in eyes with band atrophy (124).

#### **Summary box**

The new imaging modalities of the optic nerve head and RNFL thickness can describe with high accuracy the morphology of the above structures. However none of them has 100% accuracy in the diagnosis of glaucoma. RNFL thickness analysis seems to perform better than optic disc analysis. Clinical examination is of utmost importance before reaching the diagnosis of glaucomatous optic neuropathy
