Positioning value of objective analysis of macular ganglion cell complex (mGCC) in optic pathway-related neuro-ophthalmology

Background: This study aimed to explore the positioning value of objective analysis of macular ganglion cell complex (mGCC) in optic pathway-related neuro-ophthalmology diseases. Methods: This retrospective study included 32 patients with optic pathway-related neuro-ophthalmology diseases. A swept-source optical coherence tomography (SS-OCT) was used to scan and analyze the morphological characteristics of mGCC thickness and peripapillary retinal nerve �ber layer (pRNFL) thickness in these patients, and then they were compared with the visual �eld changes at the corresponding phase to analyze their relationship. Results: In optic pathway-related neuro-ophthalmologic diseases, the morphological characteristics of mGCC thickness demonstrated similar characteristic changes to that of visual �eld, and mGCC analysis remained to be objective. Conclusion: The application of SS-OCT to examine the morphological changes of mGCC thickness has position value of objective analysis in the diagnosis and treatment of optic pathway-related neuro-ophthalmologic diseases.


Background
2][3] This technique provides favorable conditions for observing the retinal ganglion cells in the optic nerve and macular area. 4,5Most of the previous OCT studies focused on observing the thickness of the optic nerve ber layer present around the optic disc and the thickness of the retinal ganglion cells in the macular area, [6][7][8][9] while studies describing the morphological characteristics of the ganglion cells in the macular area are lacking.Hence, in the present study, SS-OCT was used to examine the topographical map of macular ganglion cell complex (mGCC) thickness as well as the nerve ber thickness around the optic disc.The probability graph of atrophied disappear changes of mGCC combined with visual eld examination was adopted to analyze the changes in imaging of the optic pathway-related neuro-ophthalmologic diseases.We aimed to observe the changes in the optic nerve of the above diseases from a new imaging perspective, thereby deepening the understanding of the pathological and physiological changes of these diseases.

Methods
General data: Thirty-two patients with optic pathway-related neuro-ophthalmology diseases who visited our ophthalmology center were collected (Table 1), which included 15 males and 17 females, aged 5-77 years, and with a range of visual acuity of 20/800-20/16.Among them,12 cases had pituitary tumors, 3 had craniopharyngioma, 2 had transparent septum de ciency, 3 had hemangioma, 2 had vascular malformation, 6 had ischemia, 1 had meningioma, 1 had schwannoma, 1 had chordoma or metastatic carcinoma and 1 had other tumors.

Methods
Routine examinations including distance visual acuity, near visual acuity, intraocular pressure, slit lamp microscope, and mydriasis funduscopy were performed.In terms of visual eld examination (model750i, Carl Zeiss Meditec, Inc., Dublin, CA), an automatic visual eld analyzer was used for central 30°, 60° and 90° examinations.SS-OCT examination(Deep Range Imaging OCT, Topcon2000, Tokyo, Japan and image analysis: SS-OCT was used to analyze the morphological features in mGCC thickness map, and the peripapillary retinal nerve ber layer (pRNFL) thickness as well as its clinically signi cant probability graph of the lesions.These features were compared with the changes in the visual eld at the corresponding phase to analyze their relationship.

Results
The visual eld, mGCC atrophied disappear and lesion positioning of the 32 patients with optic pathwayrelated neuro-ophthalmology mainly showed (1) superior visual eld hemianopia based on monocular horizontal demarcation, mGCC showed inferior atrophied disappear, and the lesion could be diagnosed as optic neuropathy at the anterior lamina cribiosa (for cases 31 and 32).In case of monocular complete blindness, the mGCC was manifested as complete atrophied disappear, and the lesion could be considered as optic neuropathy between the lamina cribiosa and the optic chiasm (such as unilateral postocular neuritis, optic canal fracture).(2) For bitemporal hemianopia, the bilateral mGCC rings showed nasal atrophied disappear by taking midperpendicular bisector as demarcation, and the lesion was located at the optic chiasm (in cases 1, 2, 6, 7, 18, 22, and 23).In terms of bitemporal hemianopia and one eye crossing the midperpendicular bisector, the bilateral mGCC rings were manifested as nasal atrophied disappear by taking the midperpendicular bisector as demarcation and one eye crossed the midperpendicular bisector, and the lesion was considered as optic chiasm lesion that is biased towards one eye (in cases 4, 5, 8, 19, 20, 21, 24, 26, and 28).(3) For homonymous hemianopia without macular sparing, mGCC was manifested as nasal atrophied disappear in one eye and temporal atrophied disappear in another eye by taking the midperpendicular bisector as demarcation, and the patients were diagnosed with lesion of between the posterior optic chiasm and the middle of the optic radiation (in cases 3, 9, 14 and 25).For cases with both eyes of hemianopia towards 1/4 upper or lower quadrant, without the macula sparing, the mGCC ring was manifested as atrophied disappear at 1/4 of the lower nasal side in one eye and atrophied disappear at 1/4 of the lower temporal side in the other eye, and the lesion was located at the anterior optic radiation (such as in case 12).In terms of homonymous hemianopia with macular sparing, mGCC was manifested as nasal atrophied disappear in one eye and temporal atrophied disappear in another eye by taking the midperpendicular bisector as demarcation, and the lesion was located at the posterior optic radiation and further (in cases 10, 13, 15).For homonymous hemianopia with macular sparing and retain of contralateral 30-degree crescent, mGCC was manifested as nasal atrophied disappear in one eye and temporal atrophied disappear in another eye by taking the midperpendicular bisector as demarcation, with macular sparing, and the lesion was located in the middle of the calcarine ssure (such as in case 17).If the visual eld was symmetric and ipsilateral central hemianopia, then the mGCC appeared as nasal atrophied disappear in one eye and temporal atrophied disappear in another eye by taking the midperpendicular bisector as demarcation, with macular sparing, and the lesion was positioned at the occipital pole.Meanwhile, if the visual eld was symmetric and ipsilateral hemianopia, with the meniscal defects at the contralateral eye, then the mGCC appeared as nasal atrophied disappear in one eye and temporal atrophied disappear in another eye by taking the midperpendicular bisector as demarcation, with macular sparing, and the lesion was positioned at the anterior calcarine ssure.(4) Altered visual eld and normal mGCC ring were found in patients with short onset time, either in the latent period or during the early onset (such as in cases 27, 29, and 30), and with descending optic neuropathy of trans-neuronal lesion after optic radiation that did not induce mGCC injury, wherein the lesion positioning relied on the visual eld and MRI (in cases 11 and 16), (Figure 1).

Discussion
Optic pathway-related neuro-ophthalmologic diseases mainly included diseases of optic nerve, optic chiasm, optic tracts, optic radiation, central nervous system.The cause could be tumor, trauma, degeneration and congenital dysplasia and others.Ganglion cell complex-optic nerve is a pivotal pathway that connects the retina and the brain. 10The nerve conduction begins in the ganglion cell complex (dendrites-inner plexiform layer, ganglion cell layer, axon-neural ber layer) and nerve ber bundle, converging at the lamina cribiosa till the optic nerve.The bilateral optic nerves form an optic chiasm in the suprasellar region, and then divide into bilateral optic tracts, exchanging the neurons at the lateral geniculate nucleus (LGN).These in turn form optic radiation that projects towards the ssura calcarina, and nally the visual information is completed by the visual center in the occipital region.As the optic nerve bers travel in clear regularity, then the nasal retinal nerve bers (including the nasal part of the macula) of each eye intersect at the optic chiasm till the contralateral tract, while those at the temporal side do not intersect. 11The inferior retinal nerve bers are located in the medial optic tract after passing through the optic nerve and the optic chiasm.Hence, the optic nerve bers rotate to 90° when they enter the optic tract from the optic nerve and optic chiasm.The subnasal retinal nerve bers pass through the optic chiasm, but travel forward in the contralateral optic nerve (Wilbrand's knee) before merging with the contralateral inferotemporal non-crossing-bers and entering the optic tract. 12herefore, the diseases at different parts of optic pathway-related neuro-ophthalmology have regularity, and manifest as visual eld changes with different regularities.Meanwhile, the visual eld examination remains subjective, and is largely in uenced by the visual function, psychological factors and cognitive coordination ability of the patients.4][15] The normal mGCC manifests as a ring structure, which is an yellow ring, while the mGCC in the subnormal status or in the swelling period was manifested as a red ring.The common atrophic forms of mGCC included: 1/4 quadrant atrophied disappear, upper and lower atrophied disappear based on horizontal demarcation, binasal or concurrent homonymous atrophied disappear or complete atrophied disappear by taking the midperpendicular bisector as demarcation (Figure 2).
Through clinical diagnosis and treatment, we found that the ganglion cells were distributed in the macular region also and were precisely presented in horizontal, vertical and quadrant regularity.Speci cally, they manifest as unilateral mGCC ring atrophied disappear or mGCC atrophied disappear at the upper and lower half side based on horizontal demarcation for the lesion at anterior optic chiasm, the mGCC atrophied disappear at half of the bilateral nasal sides based on midperpendicular demarcation for the lesion at optic chiasm, and the mGCC atrophied disappear with or without macular sparing at homonymous side or 1/4 quadrant based on midperpendicular demarcation for lesion at posterior optic chiasm.The combination of MRI and 90-degree visual eld should be performed to analyze the accurate positioning of the visual pathological lesions at the posterior optic chiasm.The results showed that the visual tract lesions as well as lesions at the anterior and the middle of the optic tract were not accompanied by macular sharing, while the lesions at the posterior optic radiation and the subsequent calcarine ssure were accompanied by macular sparing.The mGCC showed atrophied disappear at 1/4 quadrant below the same name for lesions at the anterior ring of optic radiation, while showed atrophied disappear at 1/4 quadrant above the same name for lesions present in the medial optic radiation.In calcarine ssure lesions, the mGCC showed semi-asymmetric atrophied disappear in the same name with macular sparing based on midperpendicular demarcation, while appeared as symmetric ipsilateral hemianopia under 90-degree visual eld for lesions in the middle of calcarine ssure, with macular sparing and contralateral crescent sparing.The mGCC showed a crescent defect in the contralateral eye under the 90-degree visual eld for lesions in the anterior calcarine ssure, while manifested as symmetric and ipsilateral central hemianopia (Figure 3) under 90-degree visual eld for lesions at the occipital pole.
In the diseases of between the optic nerve and the optic tracts ,the visual eld , the mGCC and the pRNFL damage evolution are divided into three stages: (1) subnormal eyes at the preclinical or latent period showed normal visual acuity and visual eld, with swelling of mGCC and pRNFL; (2) subnormal eyes at the beginning of the disease that lasted for 2-3 weeks, with abnormal visual acuity and visual eld, and swelling of mGCC and pRNFL.The visual eld changes and mGCC swelling do not coincide during this period; and (3) mid-term progression and separation period that lasted for 2-3 weeks after the onset, with the occurrence of mGCC atrophied thinning, but swollen pRNFL.The visual acuity as well as the visual eld showed improvement when compared with those during the early stage of the disease.The change of visual eld in this period was basically consistent with the changes of mGCC atrophied thinning.Stabilization and atrophy period showed pRNFL atrophied disappear, which usually lasted for more than 6-8 weeks after the onset.Generally, the disease discontinued to progress and tended to stabilize after 3 months, and then showed improvement in the visual acuity and stabilized the visual eld.These changes are better than those at the initial stage, but generally do not recover to the original normal levels.At this stage, the change in the visual eld coincides with those in mGCC and pRNFL atrophied disappear.Functional changes of ganglion cells (visual eld changes) occur (in the early stage) before the organic changes of ganglion cells (middle stage).The ganglion cell body showed atrophied thinning initially (appeared after 2-3 weeks of onset), and the corresponding ganglion cell axon ber (mRNFL) also showed atrophied thinning, followed by the atrophied disappear of pRNFL (6-8 weeks after onset).
Generally, the disease becomes stable after 3 months.The time difference between atrophy of ganglion cell bodies and axons (mRNFL, pRNFL) might be related to the apoptosis of astrocytic-vascular sheath in the periphery of nerve bers that occurs after the atrophy of ganglion cell axons.
The concept and essence of subnormal eye: The latent state of the onset (clinically cured) or the non-onset optic nerve disease or the clinically cured fundus diseases are accompanied by optic nerve damage.Both types of diseases involve optic nerve damage -mGCC swelling and pRNFL swelling.Also the optic disk was stained at the later FFA stage.Therefore, the subnormal eye is essentially considered to be in the latent state (most of the cases) or early (very few) manifestation of the eye diseases, which showed association with mGCC swelling and atrophy (fundus diseases, optic neuropathy, and glaucoma).The latent sub-normal eye refers to no clinical symptoms, except for mGCC and pRNFL swelling and stained FFA optic disc during this period, with normal visual acuity and visual eld.
Therefore, it is considered as the latent period or preclinical period, which might last longer or for the whole life.Only few cases had the onset based on this.
The visual eld of trans-neuronal descending lesions at the posterior optic tracts changes from hours to weeks, and the mGCC atrophy might take several months to years to occur.Nevertheless, the evolution and the characteristics of visual eld, mGCC and RNFL in patients with trans-neuronal descending lesions at the posterior optic radiation require further investigation.

Conclusion
The distribution of ganglion cells is closely related to the visual eld.0][21][22][23][24] Since mGCC provides only 50% of neural visual information, accurate visual eld examination is still needed to improve the necessary supplement.The authors hypothesized that mGCC cannot completely replace the visual eld examination at present, and further research on mGCC is warranted.Meanwhile, the positioning of optic pathway-related neuro-ophthalmologic diseases without changes in mGCC ring in the preclinical or latent stage relies on the visual eld and the MRI, and the precise positioning of the optic lesion at the posterior optic chiasm requires combination of MRI and 90-degree visual eld.
Therefore, application of SS-OCT examination to analyze the morphological changes in mGCC thickness probability graph, and close combination of it with visual eld and MRI examination assists in mutual veri cation and brings out the best in each other, thus achieving the objective localization value in diagnosing and treating optic pathway-related neuro-ophthalmic diseases.

Open Access
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Nucci C Mancino R Martueci A et a1 3-T Diffusion tensor imaging of the optic nerve in subjects
with glaucoma correlation with GDx-VCC HRT-III and Stratus optical coherence tomography ndings Br J Ophthalmol 2012 96 (7) 976-980.The number 1 means male and the number 2 means female in the gender Figures In optic pathway-related neuro-ophthalmologic diseases, the morphological characteristics of mGCC thickness demonstrated similar characteristic changes to that of visual eld.a.Left papillitis optica:In case of monocular complete blindness, the mGCC was manifested as complete atrophied disappear.Left eye visual eld showing total blindness. .b. Ischemia at the posterior segment of the left optic radiation or in the center of the calcarine ssure.The mGCC was manifested as nasal atrophy in the right eye and temporal atrophy in the left eye in mGCC ring based on midperpendicular demarcation.The visual eld showing that Homonymous hemianopia of right side.

Figure 2 The
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Figure 3 The
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Table Table 1
Baseline patient characteristics