Longitudinal imaging of vitreal hyperreflective foci in mice with acute optic nerve damage using visible-light optical coherence tomography.

Hyperreflective foci (HRFs) appear in optical coherence tomography (OCT) images of the retina and vitreous of patients with various ocular diseases. HRFs are hypothesized to be immune cells that appear in response to ischemia or tissue damage. To accurately identify HRFs and establish their clinical significance, it is necessary to replicate the detection of similar patterns in vivo in a small animal model. We combined visible-light OCT with temporal speckle averaging (TSA) to visualize and track vitreal HRFs (VHRFs) densities for three days after an optic nerve crush (ONC) injury. Resulting vis-OCT images revealed that VHRF density significantly increased approximately 10-fold at 12 h after ONC and returned to baseline three days after ONC. Additional immunohistochemistry results confirmed these VHRFs as inflammatory cells induced from optic nerve damage.

Objective Assessment of Visual Field Defects Caused by Optic Chiasm and Its Posterior Visual Pathway Injury.

OBJECTIVES: To investigate the characteristics and objective assessment method of visual field defects caused by optic chiasm and its posterior visual pathway injury. METHODS: Typical cases of visual field defects caused by injuries to the optic chiasm, optic tracts, optic radiations, and visual cortex were selected. Visual field examinations, visual evoked potential (VEP) and multifocal visual evolved potential (mfVEP) measurements, craniocerebral CT/MRI, and retinal optical coherence tomography (OCT) were performed, respectively, and the aforementioned visual electrophysiological and neuroimaging indicators were analyzed comprehensively. RESULTS: The electrophysiological manifestations of visual field defects caused by optic chiasm injuries were bitemporal hemianopsia mfVEP abnormalities. The visual field defects caused by optic tract, optic radiation, and visual cortex injuries were all manifested homonymous hemianopsia mfVEP abnormalities contralateral to the lesion. Mild relative afferent pupil disorder (RAPD) and characteristic optic nerve atrophy were observed in hemianopsia patients with optic tract injuries, but not in patients with optic radiation or visual cortex injuries. Neuroimaging could provide morphological evidence of damages to the optic chiasm and its posterior visual pathway. CONCLUSIONS: Visual field defects caused by optic chiasm, optic tract, optic radiation, and visual cortex injuries have their respective characteristics. The combined application of mfVEP and static visual field measurements, in combination with neuroimaging, can maximize the assessment of the location and degree of visual pathway damage, providing an effective scheme for the identification of such injuries.

Longitudinal Analysis of Retinal Ganglion Cell Damage at Individual Axon Bundle Level in Mice Using Visible-Light Optical Coherence Tomography Fibergraphy.

Purpose: We developed a new analytic tool based on visible-light optical coherence tomography fibergraphy (vis-OCTF) to longitudinally track individual axon bundle transformation as a new in vivo biomarker for retinal ganglion cell (RGC) damage. Methods: After acute optic nerve crush injury (ONC) in mice, we analyzed four parameters: lateral bundle width, axial bundle height, cross-sectional area, and the shape of individual bundles. We next correlated the morphological changes in RGC axon bundles with RGC soma loss. Results: We showed that axon bundles became wider and taller at three days post ONC (pONC), which correlated with about 15% RGC soma loss. At six days pONC, axon bundles showed a significant reduction in lateral width and cross-sectional area, followed by a reduction in bundle height at nine days pONC. Bundle shrinking at nine days pONC correlated with about 68% RGC soma loss. Both experimental and simulated results suggested that the cross-sectional area of individual RGC axon bundles is more sensitive than bundle width and height to indicate RGC soma loss. Conclusions: This study is the first to track and quantify individual RGC axon bundles in vivo after ONC injury. Translational Relevance: Recognizing RGC loss at its earliest stage is crucial for disease diagnosis and treatment. However, current clinical methods to detect the functional and structural changes in the inner retina are not sensitive enough to directly assess RGC health. In this study, we developed vis-OCTF-based parameters to track RGC damage, making possible to establishing a quantifiable biomarker for glaucoma.

Progression of optic atrophy in traumatic optic neuropathy: retrograde neuronal degeneration in humans.

OBJECTIVE: We used optical coherence tomography (OCT) to document the time course of retrograde neuronal degeneration following indirect optic nerve injury. METHODS: We retrospectively studied patients diagnosed with unilateral indirect traumatic optic neuropathy (TON). Patients with total or near-total optic atrophy were included. All patients underwent complete ophthalmological examinations, including OCT imaging, within 1 day and at 1, 2, 3, 4, 6, 8, 12, 24, and 48 weeks after trauma. RESULTS: The mean thicknesses of the circumpapillary retinal nerve fiber layer (cpRNFL) and macular retinal ganglion cell-inner plexiform layer (mGCIPL) decreased significantly at 2 weeks after trauma (p = 0.027 and p = 0.043). Changes in mGCIPL thickness preceded changes in cpRNFL thickness. The rates of reduction in mGCIPL and cpRNFL thicknesses were greatest between 2 to 4 weeks and 4 to 6 weeks after trauma. The reduction in mGCIPL thickness then slowed, and stabilized at 12 weeks after trauma. The proportions of cpRNFL and mGCIPL losses at 2, 4, 6, 8, and 12 weeks compared to 24 weeks were 17.1, 33.7, 59.8, 77.9, and 87.9% and 30.0, 73.3, 76.1, 88.3, and 97.9%, respectively. CONCLUSIONS: OCT revealed optic atrophy progression 2 weeks after trauma, which was most rapid from 2 to 6 weeks, and then gradually stabilized. Loss of retinal ganglion cell bodies and dendrites seemed to precede the axonal degeneration. Observations of morphological changes in retinal layers using OCT in TON patients improve our understanding of retrograde neuronal degeneration of the central nervous system.

Afferent Visual Manifestations of Traumatic Brain Injury.

Traumatic brain injury (TBI) causes structural and functional damage to the central nervous system including the visual pathway. Defects in the afferent visual pathways affect visual function and in severe cases cause complete visual loss. Visual dysfunction is detectable by structural and functional ophthalmic examinations that are routine in the eye clinic, including examination of the pupillary light reflex and optical coherence tomography (OCT). Assessment of pupillary light reflex is a non-invasive assessment combining afferent and efferent visual function. While a assessment using a flashlight is relatively insensitive, automated pupillometry has 95% specificity and 78.1% sensitivity in detecting TBI-related visual and cerebral dysfunction with an area under the curve of 0.69-0.78. OCT may also serve as a noninvasive biomarker of TBI severity, demonstrating changes in the retinal ganglion cell layer and nerve fiber layer throughout the range of TBI severity even in the absence of visual symptoms. This review discusses the impact of TBI on visual structure and function.

Outcome of the surgical decompression for traumatic optic neuropathy: a systematic review and meta-analysis.

There exists a persisting controversy regarding the indications for optic nerve surgical decompression (ONSD) in traumatic optic neuropathy (TON). A meta-analysis is warranted to help guiding therapeutic decisions and address gaps in knowledge. The authors conducted a search of PubMed and MEDLINE electronic databases. Primary endpoint was the improvement in the visual function with ONSD in comparison with the conservative management. Secondary endpoint was visual function improvement when surgery was performed within the first 7 days. A random effects model meta-analysis was conducted. Data from each study were used to generate log odds ratio and 95% confidence intervals, to compare post-operative visual improvement. Nine studies met the inclusion criteria for analysis, comprising 766 patients. Visual improvement occurred in 55% (198/360) of patients treated with ONSD, and in 40% (164/406) of those who underwent conservative treatment. Forest plot revealed significant differences in the visual function improvement among these two groups, although further analysis revealed the studies were heterogeneous (log OR, 0.81; CI, 0.07-1.55; I2, 62.8% p = 0.015). Overall, patients who underwent early surgery had better visual outcomes (log OR, 0.94; CI, 0.29-1.60; I2, 0% p = 0.9). ONSD is an effective technique to improve the outcome in the visual function in patients with TON. A lack of randomized controlled trial-and inherent surgical selection and publication bias-limits direct comparison between surgical decompression and conservative management. Suitably designed prospective cohort studies may be useful in identifying patients more likely to receive benefit from ONSD.

Combination analysis on the impact of the initial vision and surgical time for the prognosis of indirect traumatic optic neuropathy after endoscopic transnasal optic canal decompression.

To analyze the impact of the initial vision and surgical time for endoscopic transnasal/transethmosphenoid optic canal decompression (ETOCD) in the treatment of indirect traumatic optic neuropathy (TON). This retrospective case series analysis included 72 patients with indirect TON who underwent ETOCD from August 2017 to May 2019. Visual acuity (VA) was compared before and after surgery to estimate the improvement rate. The overall VA improvement rate of ETOCD was 54.2%. There were 83.3% and 33.3% improvement rate of patients with residual vision and blindness, respectively. VA was improved in 60.9% of patients treated within 3 days, 61.5% treated within 7 days, and 35.0% treated later than 7 days. Of the blindness patients, 50.0%, 37.5%, and 0.0% were treated within 3 days, 3-7 days, and later than 7 days, respectively. Of patients with residual vision, 85.7%, 92.3%, and 70.0% were treated within 3 days, 3-7 days, and later than 7 days, respectively. A statistically significant difference was found between patients with residual vision and those with blindness (P < 0.01), as well as between patients who received ETOCD within 7 days and those who received ETOCD later than 7 days (P = 0.043). The improvement rate of blindness patients managed within 3 days (P = 0.008) and 3-7 days (P = 0.035) was significantly higher than that for patients managed beyond 7 days. Indirect TON patients can directly benefit from ETOCD, and patients with residual vision have better improvement rates. ETOCD should be performed as soon as possible to salvage the patient's VA, especially within the first 7 days. For blindness patients, it is necessary to carry out the surgery within 7 days with increased benefit seen before 3 days.

CT Features of Posttraumatic Vision Loss.

Clinical evaluation of patients with trauma is challenging, especially in the presence of neurologic injuries. Vision loss after trauma is a harmful and usually overlooked consequence that may be avoided with a prompt and accurate intervention. Head CT is commonly performed in patients with trauma. However, radiologists may be unfamiliar with the CT findings associated with injuries that may affect eyesight. Understanding the visual pathway anatomy and its critical landmarks is paramount for recognizing these findings. This article describes the use of head CT to evaluate the visual pathway to help avoid vision loss in patients with trauma. Injuries are presented in terms of those affecting the globe (rupture, hemorrhage, and lens trauma), optic nerve (direct and indirect traumatic optic neuropathy), orbit (orbital compression syndrome), and vasculature (traumatic carotid-cavernous sinus fistula and posterior cerebral artery injury or ischemia). Techniques for measuring the globe on CT to assess for injury are illustrated. Indications for screening CTA of the head and neck in patients with suspicion for blunt traumatic vascular injury are summarized. Emphasis is placed on the CT findings that warrant an emergency intervention to prevent traumatic visual impairment.

[Traumatic optic pit-Optic nerve evulsion caused by indirect ocular trauma]. / Traumatische Grubenpapille ­ Evulsio nervi optici durch indirektes Bulbustrauma.

This article describes the case of a 28-year-old man who suffered an optic nerve evulsion (ONE) after falling from a height of 5 m. On admission visual acuity in the affected left eye was light perception, direct pupillary reaction was unresponsive, and the eye was hypotonic. Because of deep eyelid laceration, hyphemia and severe vitreous hemorrhage a globe rupture was suspected and a surgical exploration with vitrectomy was performed. This resulted in the detection of an ONE. During the following 24 months a painful eyeball due to secondary glaucoma developed and enucleation of the eye became necessary.

Traumatic Globe Subluxation Accompanied by Traumatic Optic Neuropathy.

A 52-year-old, alcohol-intoxicated woman suffered periorbital trauma to the left eye and presented to the emergency department with proptosis and complaints of decreased vision in the left eye. Physical examination revealed loss of light perception (LP), relative afferent pupillary defect (RAPD), pupil dilatation, and corneal epithelial defect of the left eye. In addition, the fundus of the left eye was not easily visible due to severe corneal abrasion and edema, but there was no retinal detachment or vitreous hemorrhage on B-scan ultrasonography. Hertel exophthalmometric values differed by 7 mm between the eyes and measured 13 mm in the right eye and 20 mm in the left eye. In addition, she had severely limited left eye movement in all directions. Computerized tomography (CT) imaging of the orbit showed that the left optic nerve extended 15 mm further than the optic nerve of the right eye and retrobulbar hemorrhage of the left eye. The patient underwent emergency lateral canthotomy, cantholysis, and conjunctival incision to release the optic nerve extension and reduce the eyeball subluxation of the left eye. An intraoperative examination demonstrated that all extraocular muscles of the left eye were intact. The left eyeball returned to its normal position after surgery. Two days after surgery, proptosis of the left eye improved significantly, and there was no difference in Hertel exophthalmometric values between the eyes, both eyes measured 13 mm. However, the patient continued to suffer LP, RAPD, and pupil dilatation of the left eye.

Imaging review of ocular and optic nerve trauma.

Traumatic ocular injuries account for a substantial number of emergency department visits annually and represent a significant source of patient disability. A thorough understanding of ocular/optic nerve anatomy and traumatic pathology is fundamental in the accurate and efficient interpretation of emergency neuroradiology. This article will review relevant anatomy, imaging protocols, clinical symptomatology, and key imaging findings associated with the broad spectrum of traumatic ocular and optic nerve pathology.

Conservative Management of Traumatic Optic Neuropathy Secondary to Lateral Orbital Wall Fracture.

PURPOSE: To inform rural healthcare providers about the early identification and management of traumatic optic neuropathy (TON). Specifically, we seek to legitimize expectant management as a viable approach to such cases. OBSERVATIONS: A 27-year-old female with direct posterior compressive TON with associated visual field and visual acuity deficit was managed expectantly without steroids or surgical intervention. In four months, her visual acuity improved from 20/400 to 20/50. CONCLUSTION AND IMPORTANCE: Although steroids and surgery have been common practice for treatment of TON, there is insufficient evidence to support their use in all cases. Existing research supports expectant management as a viable option. This could prove especially useful in rural settings where resources and surgical subspecialists are limited.

Usefulness of MRI Slices Parallel to the Optic Chiasma in a Case with Traumatic Optic Nerve Avulsion after a Bear Attack.

Optic nerve avulsion is an exceedingly rare condition. Here, we describe a case of optic nerve avulsion in a 74-year-old man with temporal hemianopia in the contralateral eye after a bear attack. Magnetic resonance imaging (MRI) revealed separation of the optic nerve distal to the optic chiasma, whereas the high signal in diffusion-weighted imaging suggested nerve injury from the left side of the optic chiasma to the left optic tract. MRI slices parallel to the optic chiasma were obtained and used for evaluating the site of optic nerve avulsion and nerve injury, which were responsible for temporal hemianopia in the contralateral eye.

Magnetic resonance imaging indicator of the causes of optic neuropathy in IgG4-related ophthalmic disease.

BACKGROUND: The following study investigates the involvement of optic neuropathy in IgG4-related ophthalmic diseases (IgG4-ROD) based on the magnetic resonance imaging (MRI) data, and different imaging features of IgG4-ROD related optic neuropathy related to other orbital diseases. METHODS: This retrospective study included 225 patients with IgG4-RD admitted at two ophthalmology centers between January 2014 and December 2017. Twenty-six patients had both pre-therapeutic orbital MRI and optic never injury. The causes of optic neuropathy were analyzed, and the special sign in MRI to diagnose IgG4-ROD was also evaluated. RESULTS: Twelve cases had inflammation of the optic nerve sheath, while 14 cases had compression due to extraocular muscles and pseudo tumor masses. Two cases had hypertrophic cranial pachymeningitis, while one case had hypophysis involving optic chiasma. CONCLUSION: The most common causes of optic nerve injury in IgG-4 ROD are inflammation of optic nerve sheath, compression of extraocular muscles, pseudo tumor mass and hypertrophic cranial pachymeningitis, and hypophysis involving optic chiasma.

Optical Coherence Tomography Angiography in Mice: Quantitative Analysis After Experimental Models of Retinal Damage.

Purpose: We implemented optical coherence tomography angiography (OCT-A) in mice to: (1) develop quantitative parameters from OCT-A images, (2) measure the reproducibility of the parameters, and (3) determine the impact of experimental models of inner and outer retinal damage on OCT-A findings. Methods: OCT-A images were acquired with a customized system (Spectralis Multiline OCT2). To assess reproducibility, imaging was performed five times over 1 month. Inner retinal damage was induced with optic nerve transection, crush, or intravitreal N-methyl-d-aspartic acid injection in transgenic mice with fluorescently labeled retinal ganglion cells (RGCs). Light-induced retinal damage was induced in albino mice. Mice were imaged at baseline and serially post injury. Perfusion density, vessel length, and branch points were computed from OCT-A images of the superficial, intermediate, and deep vascular plexuses. Results: The range of relative differences measured between sessions across the vascular plexuses were: perfusion density (2.8%-7.0%), vessel length (1.9%-4.1%), and branch points (1.9%-5.0%). In mice with progressive RGC loss, imaged serially and culminating in around 70% loss in the fluorescence signal and 18% loss in inner retinal thickness, there were no measurable changes in any OCT-A parameter up to 4 months post injury that exceeded measurement variability. However, light-induced retinal damage elicited a progressive loss of the deep vascular plexus signal, starting as early as 3 days post injury. Conclusions: Vessel length and branch points were generally the most reproducible among the parameters. Injury causing RGC loss in mice did not elicit an early change in the OCT-A signal.

Imaging and Differentiation of Retinal Ganglion Cells in Ex Vivo Experimental Optic Nerve Degeneration by Differential Interference Contrast Microscopy.

Purpose: Apoptotic loss of retinal ganglion cells (RGCs) is involved in various optic neuropathies, and its extent is closely related to visual impairment. Direct imaging and counting of RGCs is beneficial to the evaluation of RGC loss, but these processes are challenging with the conventional techniques, due to the transparency and hypo-reflectivity of RGCs as light-transmitting structures of the retina. Differential interference contrast (DIC) microscopy, which can provide real-time images of transparent specimens, is utilized to image neuronal cells including RGCs in the ganglion cell layer (GCL). Methods: Herein, we show that the neuronal cells within each GCL in an explanted rat retina, including the inner nuclear layer and the outer nuclear layer, can be imaged selectively by transmission-type DIC microscopy. RGCs were also differentiated from non-RGCs by the objective method. Results: RGCs were differentiated from non-RGCs in the GCL by their morphological features on DIC images with the aid of retrograde fluorescence labeling. Loss of RGCs was detected in optic-nerve-transection and retinal-ischemia-reperfusion models by DIC imaging. The images obtained from the reflection-type DIC microscopy were comparable to those from the transmission-type DIC microscopy. Conclusions: This method enables direct optical visualization of RGCs in experimental optic-nerve degeneration, thus providing the opportunity for more accurate evaluation of optic neuropathies as well as more effective investigation of diseases.