Optic Neuropathies

Abstract

Optic nerve can be affected by various etiologies of optic neuropathies, and it can appear swollen or pale depending on etiology and duration of the disease. These etiologies are inflammation, ischemia, malignancy, idiopathic intracranial hypertension, toxins, and nutritional deficiency. Peripapillary optical coherence tomography (OCT) is widely performed to detect these diseases and monitor them based on the changes in peripapillary retinal nerve fiber layer (RNFL) thickness. Therefore, nowadays this modality of imaging has become a routine test in follow-up of optic nerve diseases. In this chapter, clinical examinations and main findings of peripapillary OCT in common optic neuropathies are discussed.

1. Introduction

The new generations of optical coherence tomography (OCT) can reproduce the description of optic disc (including its margin, cup, and rim areas) and makes a quantitative analysis of its surrounding structures, including peripapillary retinal nerve fiber layer (RNFL) thickness in different sectors and quadrants.

OCT is a good diagnostic tool for acquired and congenital optic nerve head diseases. In addition, it can be used for monitoring peripapillary RNFL thickness in some conditions including glaucoma and chronic papilledema. OCT is not only useful in the analysis of the optic nerve disorders but also in some of the central nervous system diseases that impact the optic nerve, too.

About the principles of the optic nerve head OCT, in brief, at first it determines the margin of optic disc automatically, even in patients with peripapillary atrophy. The optic disc size between 1.3–2.5 mm² is considered standard, and outside of this range, all measurements represent in gray. Then, the device’s software identifies the two most refractive zones of the retina, including the RNFL as the inner boundary and the pigment epithelium as the outer boundary of the peripapillary area, and the thickness of the peripapillary nerve fibers is measured at 3.4 mm from the center of the optic. In optic nerve head OCT printouts, strong reflection of peripapillary layers demonstrates that layers are perpendicular to the light of the imaging device. In contrast, areas with low reflection represent parallel layers with the light (Figure 1). The RNFL OCT scan maps represent A-scan data of the RNFL thickness from the center of the optic disc. Furthermore, ganglion cell-inner plexiform layer (GC-IPL) can be scanned, too. In these maps, the RNFL thickness measurements are compared against age-matched normative values. An area where the RNFL thickness is <5% compared to the normal values is shown in yellow and < 1% is shown in red. Before interpretation of the RNFL thickness in these maps, it is necessary to evaluate their accuracy by controlling IPL and RNFL segmentation lines and also quality score of the images (Figure 2) [1].

Figure 1.

White arrow: high reflective layers (perpendicular to the light of the OCT device). Red arrow: low reflective layers (parallel to the light).

Figure 2.

Peripapillary OCT: green circle: quality score, red arrow: IPL segmentation line, blue arrow: outer boundary of RNFL.

Analysis of the results of optic nerve head OCT needs careful interpretation due to the imaging technique complexity, different aspects of optic nerve head diseases, and potential artifacts. Furthermore, glaucomatous optic neuropathy can mimic neuro-ophthalmology disorders, making challenges in the proper diagnosis.

Some factors may affect the resolution and reliability of optic nerve head OCT images. First, the signal strength (as a quality expresser) of the images must be assessed. For example, it must be >6/10 with the Cirrus™ HD-OCT (Carl Zeiss) device or > 50 with the Optovue (RTVue) device. A poor signal leads to poor quality and misidentification of peripapillary RNFL and their measurements. Second, motion artifacts due to eye movements may cause poor quality, but new devices have programs to resolve this common problem. Third, some ocular conditions may lead to false detection and measurement of peripapillary RNFL. These conditions are including significant cataracts, dense posterior capsular opacity, or increased axial length in pathologic myopia that may influence the measurements [2].

2. Optic neuropathies

2.1 Optic neuritis

Optic neuritis typically occurs in young females, with subacute monocular visual impairment that develops over days. Painful eye movements may present precedes vision impairment. The retrobulbar form (in which the optic disc appears normal) occurs in 2/3 of cases. The most common cause of retrobulbar optic neuritis is multiple sclerosis. In 1/3 of optic neuritis cases, the inflammation involves the anterior portion (papillitis) [3].

During the acute phase of optic neuritis, the RNFL thickness sometimes increased due to mild amounts of edema, which is not clinically detectable. Scatter thinning of the RNFL occurs later until month six after the crisis of the disease (Figure 3). In some cases, visual field and OCT parameters may deteriorate and lead to RNFL atrophy [3].

Figure 3.

Retrobulbar optic neuritis: A: optic disc seems to be normal. B: central scotoma is visible. C: OCT shows impairment in the temporal sectors of each eye.

2.2 Papilledema and pseudo papilledema

Optic disc edema describes swelling of the optic nerve head anterior to the lamina cribosa. When disc edema is the result of elevated intracranial pressure, it is labeled papilledema (Figure 4).

Figure 4.

Swelling of both optic discs (green arrows) in a patient with papilledema.

OCT can be used for differentiating disc edema from pseudo-disc edema. The mean RNFL thickness is significantly greater artificially in patients with true papilledema compared with pseudo papilledema (Figures 5 and 6) [4]. But, RNFL assessment by OCT in monitoring optic nerve injury in these patients has some limitations including inaccuracies in detecting true RNFL boundaries in severe cases and identification of coexisting optic atrophy in chronic and long-lasting cases. In these situations ganglion cell complex imaging modality is helpful. This modality of imaging measures the thickness of ganglion cells and inner plexiform layers instead of just RNFL thickness, which may affect by axonal edema (Figure 7) [5]. In OCT angiography (OCTA), dilation and tortuosity of the superficial peripapillary vessels can be detected in acute phases of the disease (Figure 8).

Figure 5.

OCT B-scan of acute papilledema: increased peripapillary thickness with Bruch membrane sloping inward toward the vitreous space of the both eyes (red arrows).

Figure 6.

OCT of acute papilledema: increased RNFL thickness (right eye more than the left): The RNFL edema of the right eye is caused off-the-chart pattern.

Figure 7.

GCC imaging, 3 months after acute papilledema: the imaging shows a decrease in GCL and IPL layers at temporal and inferior sectors of the right eye.

Figure 8.

OCTA of acute papilledema: A and B, Superficial OCTA of both eyes reveal dilation and tortuosity of the superficial peripapillary vessels. C and D, OCT-B scans shows both optic disc elevation.

One of the causes of pseudo papilledema is optic nerve head drusen (ONHD) which presents with bulblike bodies in the optic nerve head. These bodies may be buried and may consider as true optic disc swelling (Figure 9) [6]. In individuals with ONHD, RNFL thickness tends to decrease in quadrants in which drusen are most aggregated (Figure 10) [7]. The suggested imaging modalities for differentiating pseudo from true optic disc swelling are optic nerve head B-scan ultrasonography, fluorescein angiography (FA), and OCT [8, 9, 10, 11]. In patients with ONHD, ocular B-scan ultrasonography with low gains can detect hyperechoic bodies in the optic nerve head [8]. In autofluorescence, hyperreflective foci can be detectable on the disc. Furthermore, in FA of cases with ONHD just staining of the bodies without leakage is the most common finding, in contrast to the conditions with true optic disc swelling that leakage is common [10, 11, 12]. In OCT, most drusens are detected as hypo or hyperreflective signal masses surrounded by hyper-reflective margins. By using OCT, more information about depth of the drusen, its morphology, and its association with surrounding structures can be obtained. In addition, small buried deep drusens can be detected by OCT (Figure 11) [13]. OCTA is a noninvasive imaging modality that could be useful in differentiating challenging cases of optic disc edema [14, 15, 16, 17, 18]. Previous studies showed in eyes with true axonal swelling due to papilledema, some vessel density values may differ from eyes with pseudo papilledema, but these changes are not consistent [16].

Figure 9.

Bilateral optic nerve head drusen: "lumpy bumpy" appearance of both optic discs with refractile bodies in the disc margins (white arrows).

Figure 10.

OCT of bilateral ONHD: Normal RNFL thickness in the right eye with a decrease in temporal RNFL sector of the left eye.

Figure 11.

Optic disc drusen: A, B-scan ultrasonogram, reveal a focal high reflective (due to calcification) elevation within the optic disc (arrow), which persists when the gain is decreased. B, hyper autofluorescence of the drusens are shown (arrow). C, in FA, staining of the drusens without leakage in late phase is detected. D, OCT shows a focal hyper reflective mass (white arrow) with nasal elevation of the optic disc.

2.3 Anterior ischemic optic neuropathy

Anterior ischemic optic neuropathy (AION) is the most common acute optic neuropathy in patients more than 50 years of age. Patients experience painless monocular vision loss that develops over hours to days. AION is classified as either arteritic (AAION), in which case it is associated with vasculitis, most commonly giant cell arteritis (GCA), or nonarteritic (NAION) [19].

In fundus examination of affected eye, optic disc swelling with peripapillary hemorrhage can be detected. In AAION type, the optic disc seems more pallor in comparison to the NAION type (Figure 12). In acute phase of the disease, peripapillary OCT will be showed diffuse edema of RNFL. In chronic phases, the disc and peripapillary area will be atrophic with pale disc and decreased RNFL thickness in OCT of optic nerve head (Figure 13) [20]. In FA leakage from the disc can be detected in late phases (Figure 14). Although RNFL thickness may increase in both acute NAION and papilledema, by using OCTA these conditions may differ from each other. In eyes with acute NAION due to ischemic condition, some vessel density parameters may decrease, in contrast to conditions without ischemia including acute papilledema (Figure 15) [21].

Figure 12.

AION: fundus photography showing atrophy of the right optic disc (old AION) and hyperemic swelling of the left optic disc, with a splinter hemorrhage (acute AION).

Figure 13.

Peripapillary OCT shows decrease in RNFL thickness at superior and inferior sectors of the right eye (old AION), with diffuse peripapillary RNFL edema of the left eye (acute AION).

Figure 14.

Acute AION: FA of the right eye shows leakage from the disc in late phase with choroidal filling delay at the nasal side.

Figure 15.

Acute AION of right eye: a, superficial OCTA right eye demonstrates dilation and tortuosity of the nasal capillaries (red arrows). On the temporal side, dark areas compatible with capillary drop out (white arrow). c, the B-scan OCT shows the disc elevation. In the fellow eye (b and d), the peripapillary capillaries seems to be normal with normal contour of the disc.

2.4 Infiltrative optic neuropathy

The optic nerve can become infiltrated by primary or secondary tumors and inflammatory processes. Metastases can reach the optic nerve by these routes:

1. from the choroid.

2. by vascular dissemination.

3. by invasion from the orbit.

4. from the central nervous system.

The most common metastatic tumors to the optic nerve are adenocarcinomas:

• In females, breast and lung cancers are the most common causes.

• In males, carcinomas of the lung and intestinal tract are the most common causes.

• When the metastasis is located in the orbital portion of the optic nerve:

• The optic disc is usually swollen.

• A yellow-white infiltrative mass can be seen on the optic disc that protruded from the surface of the nerve (Figure 16).

• Sometimes tumor cells can be seen in the vitreous body.

Figure 16.

Infiltrative optic neuropathy: fundus photography of both eyes. The right eye, optic disc swelling with obscuration of blood vessels and prepapillary flamed shape hemorrhage. A large yellowish infiltrative mass, with disruption of the architecture of the optic disc is seen on that. The left eye seems to be normal.

B-Scan ultrasonography can reveal abnormal increase in the optic nerve sheath diameter. In peripapillary OCT, an increase in RNFL thickness can be detected. FA of the affected eye may detect a hyperfluorescent mass on the optic disc with no sign of leakage (Figure 17) [22, 23].

Figure 17.

Infiltrative optic neuropathy: A, peripapillary OCT of both eye. The right eye, increased thickness of RNFL in all four quadrants. The left eye, normal RNFL thicknesses in all sectors. B, B-scan ultrasonography of the right eye reveals abnormally increased optic nerve sheath diameter (red double-headed arrows). C, in FA a hyperfluorescent mass on the right optic disc with no evidence of leakage is visible.

2.5 Toxic optic neuropathy

Toxic optic neuropathies typically present with a gradually progressive, bilaterally symmetric, painless vision loss affecting central vision. Poisoning with heavy metals like lead can cause toxic optic neuropathy. Patients can be presented with bilateral optic disc swelling and peripapillary hemorrhage, which can be confirmed in peripapillary OCT imaging (Figures 18 and 19). In visual field analysis, patients may have cecocentral or central scotomas. In FA leakage from the optic nerve head can be detected (Figure 20) [24].

Figure 18.

Acute toxic optic neuropathy in a patient with lead poisoning: fundus photographs show significant hyperemia and edema of both optic discs.

Figure 19.

Peripapillary OCT of a patient with lead poisoning: increased RNFL thickness in all sectors in both eyes is visible, suggestive of bilateral disc edema.

Figure 20.

FA of the same patient with lead poisoning: both discs have leakage, suggestive of bilateral disc swelling.

2.6 Leber hereditary optic neuropathy

Leber hereditary optic neuropathy (LHON) is the most common inherited mitochondrial disorder and typically affects young males. It typically begins as a unilateral progressive optic neuropathy with sequential involvement of the fellow eye months to years later. Fundus examination may initially reveal normal or pseudo-edematous optic nerves and telangiectatic peripapillary vessels (Figure 21) [25]. In late phases, the affected optic disc becomes pale and atrophic. Peripapillary OCT shows axonal swelling, which occurs during the acute phase of the disease (Figure 22). Furthermore, OCT clearly detects atrophy of the RNFL following the acute event [26]. In some asymptomatic eyes, OCT may demonstrate an increased RNFL thickness of the temporal quadrant (papillo-macular bundle). In FA of acute involved optic nerve head, no leakage is detected. OCTA may reveal peripapillary telangiectasia in acute phase, followed by capillary dropout, especially in the papillo-macular bundle and also disc cupping (Figure 23) [27].

Figure 21.

LHON: right optic disc seems to be elevated with peripapillary telangiectatic vessels. About the left optic disc, it has mild temporal pallor.

Figure 22.

OCT of LHON: mild peripapillary sectoral RNFL edema in both eyes with a decrease in temporal sector of peripapillary RNFL thickness in the left eye.

Figure 23.

OCTA of LHON: A, B, C, acute phase of the disease. Optic disc is hyperemic with peripapillary telangiectatic vessels. C, E, F, three months after the onset of the signs, significant capillary dropouts in the temporal side (papillo-macular bundle) and disc cupping are visible.

2.7 Optic pit

Optic pit is a kind of excavated optic disc anomaly. An optic pit is a depression of the optic disc surface that is often gray or white. It is located infero-temporally, and associated with a mild visual field defect (usually paracentral or arcuate) (Figure 24). A reduction in RNFL thickness in the excavated sector of the affected optic disc can be seen in peripapillary OCT (Figure 25). Serous detachment of the macula develops in 25–75% of optic pit cases, possibly related to liquefied vitreous entering the subretinal space through communication between the optic pit and the macula [28, 29].

Figure 24.

Fundus photography of both eyes: a yellow-whitish excavation at the inferotemporal rim of the optic disc of right eye. The left optic disc seems to be normal.

Figure 25.

A significant reduction in RNFL thickness in the temporal sector of right eye is visible. Coloboma is clearly seen on vertical OCT scan as well as horizontal scans through right optic pit.

3. Conclusion

By optic nerve head OCT, different structures are being studied and measured. This imaging modality can analyze not only layers’ thickness but also their contents.

Peripapillary OCT is widely used to detect optic neuropathies. Changes in peripapillary RNFL thickness are important in serial OCTs. This modality of imaging is available and enough reliable in diagnosis of optic nerve head diseases in routine clinical practice.

Although optic nerve head OCT is developing constantly, we cannot replace it with other tests including visual field analysis, especially in glaucoma patients.

A combination of OCT and OCTA findings will allow an understanding of complex pathologies involving the optic nerve head and peripapillary areas.

Acknowledgments

I thank Dr. Kaveh Abri Aghdam for sharing the images.

Conflict of interest

The author has no conflict of interest to declare.