**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].

#### **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**).

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

#### **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.*

#### **Figure 4.**

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

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**).

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 [8–11]. In patients with ONHD, ocular B-scan ultrasonography with low gains can detect hyperechoic bodies in the optic

#### **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.*

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

#### **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.*

#### **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.*

that leakage is common [10–12]. 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

#### **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.*

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 [14–18]. 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].

#### **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

#### **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).*

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].

#### **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:


#### **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.*

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


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].

### **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

#### **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.*

#### **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.*

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

#### **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.*

have cecocentral or central scotomas. In FA leakage from the optic nerve head can be detected (**Figure 20**) [24].
