Optical Coherence Tomography and Neuro-Ophthalmology

Virtual Issue Optical Coherence Tomography and Neuro-Ophthalmology John J. Chen, MD, PhD O ver the past decade, the Journal of Neuro-Ophthalmology has published approximately 70 articles pertaining to optical coherence tomography (OCT). In addition, OCT is used in almost every article describing an optic neuropathy since 2006 and, therefore, there are a countless number of articles that mention OCT. This is an amazing amount of literature considering that OCT has only been commercially available since 2002. Various versions of OCT machines are now found in almost every ophthalmology and neuro-ophthalmology clinic and have become essential in facilitating the ability to diagnose and monitor many retinal and optic nerve disorders. The initial OCT machines used time-domain technology and had lower resolution, but still allowed for measurement of the peripapillary retinal nerve fiber layer (RNFL) (1). This led to improved detection of optic neuropathies, including glaucoma and nonglaucomatous optic neuropathies. The technology of OCT has been continuously improving, resulting in faster scans, better resolution, and improved analysis of the data, which were discussed in several reviews (2-4). These advances have led to the ability to segment and measure the thickness of the macular ganglion cell-inner plexiform layers, which has many applications in neuro-ophthalmology that were detailed by both Kardon and Lam (5,6). A recent study reported the use of multicolor imaging to view various layers of the retina and optic nerve (7). OCT is very useful in the setting of papilledema, which was reviewed in an article by Kardon (8), "Optical coherence tomography in papilledema: what am I missing?" OCT can be used to measure the RNFL thickness and quantify the amount of optic disc edema. In addition, analysis of the macula and the ganglion cell layer allows for the ability to detect and monitor optic neuropathy in the presence of disc edema. A recent article reported thinning of the macula in the setting of resolving papilledema, especially in patients with atrophic papilledema (9). Two separate studies showed that retinal ganglion cell layer loss precedes RNFL thinning in optic neuritis (10) and nonarteritic anterior ischemic optic neuropathy (11). Department of Ophthalmology, Mayo Clinic Rochester, Rochester, Minnesota. Address correspondence to John J. Chen, MD, PhD, Department of Ophthalmology, Mayo Clinic Rochester, Rochester, MN 55905; Email: [e-mail] Chen: J Neuro-Ophthalmol 2018; 38: e5-e8 The orientation of Bruch membrane and the retinal pigment epithelium (RPE) has been shown to be helpful in differentiating papilledema for other optic neuropathies. With raised intracranial pressure, there is an upward deflection of peripapillary RPE and Bruch membrane on OCT, which normalizes when papilledema resolves (12,13). Sibony et al (14) found that the peripapillary RPE also has an upward deflection toward the vitreous in patients with optic nerve sheath meningioma. By contrast, a backward deflection of the lamina cribrosa from low intracranial pressure may be detected in normal tension glaucoma (15). OCT is critical in providing insight into the structural causes for glaucoma and differentiating glaucoma from nonglaucomatous optic neuropathy (16,17). In addition to changes in the lamina cribrosa orientation, enhanced depthOCT has demonstrated that the lamina cribrosa tends to be thinner with more focal defects in normal tension glaucoma compared with high-pressure glaucoma (18,19). OCT is helpful in diagnosing and monitoring optic disc drusen. A study using spectral-domain OCT showed that OCT was helpful in differentiating optic disc drusen from papilledema (20). Enhanced depth imaging and swept source OCT allow for deeper imaging and were shown to improve detection and imaging of optic nerve head drusen (21). A recent study showed that peripapillary RNFL thinning correlated with the anatomic location of optic disc drusen and visual field defects, especially in patients with superficial optic disc drusen (22). OCT can be used to localize lesions along the visual pathway. Thinning of the macular ganglion cell layer is seen early in cases of toxic and nutritional optic neuropathy, which supports the concept that the papillomacular bundle is primarily damaged in this optic neuropathy (23). OCT also is helpful in detecting chiasmal injury. A case report discussed the use of OCT to identify the chiasmal hypoplasia variant of septo-optic dysplasia, causing thinning of the nasal and temporal quadrants of the peripapillary RNFL, in contrast to glaucoma that tends to affect the superior and inferior poles (24). Although the pattern of the RNFL thinning can sometimes detect chiasmal injury, a recent study evaluating chiasmal compression from tumors showed that analysis of the macular ganglion cell complex is more sensitive than measurement of the peripapillary RNFL (25). Chiasmal compression from tumor leads to a preferential thinning of the macular ganglion cell complex in the nasal hemiretina e5 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Virtual Issue (8,26,27). Analysis of the macular ganglion cell complex also can help predict visual recovery following pituitary tumor surgery, where patients with less ganglion cell loss have better postoperative visual field results (25). While binasal thinning of the macular ganglion cell layer is seen in chiasmal injury, optic tract lesions cause homonymous hemimacular thinning, which was seen in a case report of optic tract injury from neuromyelitis optica (28). In 2 studies, OCT demonstrated that isolated occipital lesions may cause transsynaptic retrograde retinal degeneration and homonymous ganglion cell complex thinning (29,30). In contrast to optic tract lesions, where thinning is seen within weeks of injury, transsynaptic retrograde degeneration likely takes many months or years to develop. The observation of transsynaptic retrograde degeneration has implications in using OCT in neurodegenerative conditions. OCT has been proposed as a method of monitoring neurodegenerative diseases where the eye serves as the "window to the brain." Iseri et al (31) showed RNFL and inner retinal thinning in patients with Alzheimer disease, which correlated with the severity of cognitive impairment. OCT studies also have demonstrated inner retina, ganglion cell complex, and RNFL thinning in patients with Parkinson disease (32-34), where the extent of thinning may correlate with the severity and duration of the disease. One article showed that there may be subclinical visual dysfunction in patients with Parkinson disease, which correlates with thinning of the ganglion cell layer (35). OCT has been extensively used to study subjects with multiple sclerosis (MS) (36-39) and neuromyelitis optica spectrum disorder (NMOSD) (40,41). Davies et al (42) showed that patients with MS have a thinner ganglion cell complex thickness, especially if they had prior optic neuritis. Optic neuritis leads to thinning of the peripapillary RNFL in both NMOSD and MS. While NMOSD related optic neuritis tends to cause more thinning of the RNFL than MS-related optic neuritis (43,44), a study by Lange et al (41) revealed that there is an overlap between the 2 groups, and therefore RNFL alone is unable to differentiate the 2 forms of optic neuritis. In addition, patients with MS without clinical episodes of optic neuritis have been reported to have progressive thinning of the RNFL on OCT (45,46). Abalo-Lojo et al (46) found that RNFL thickness correlated with brain atrophy and disability scores in patients with MS, and thus OCT has been proposed as a method to monitor MS disease progression. Studies on subclinical RNFL loss in NMOSD are mixed in the literature, including those published within the Journal of Neuro-Ophthalmology (43). Interestingly, a 4-year observational study of 9 patients with NMOSD without optic neuritis did not demonstrate thinning of the RNFL over time, suggesting that the lack of progressive thinning of the RNFL could be used to distinguish NMOSD from MS (47). However, a study by Brody e6 et al (48) found that patients with NMOSD can have subclinical optic neuritis. OCT is now an outcome measure of most clinical trials involving the optic nerve, including the idiopathic intracranial hypertension treatment trial (49-51), venous stenting for idiopathic intracranial hypertension (52), nonarteritic anterior ischemic optic neuropathy (53) and MS (37). OCT allows for visualization of all layers of the retina and has provided insight into some disease processes. For example, 2 OCT studies showed outer plexiform layer retinal edema and subfoveal detachments in neuroretinitis, which suggests that the submacular detachments in neuroretinitis result from diffusion of fluid from the optic disc to the outer plexiform layer and through the outer limiting membrane to the subretinal space (54,55). In addition, OCT is important in documenting the ocular changes that occur during space flight, including optic disc edema and choroidal folds (56,57). Because OCT is very sensitive in detecting optic atrophy, it has been used to detect and monitor optic neuropathies in inherited conditions. Case reports and series showed that patients with Friederich ataxia (58), spastic ataxia of Charlevoix-Saguenay (59), spinocerebellar ataxia 7 (60), and panthothenate kinase-associated neurodegeneration (61) all have RNFL thinning on OCT. One article showed central retinal thinning of the retina and disorganized photoreceptor layers on OCT in patients with spinocerebellar ataxia Type 1 (62). While OCT is critical for the analysis of the optic nerve and retina and has revolutionized our ability to diagnose and track diseases, proper interpretation of the scans is important (63). There can be artifacts on OCT leading to misinterpretation of the imaging data. The most common artifacts of OCT were reviewed by Chen and Kardon (64). Failure to recognize these can lead to misdiagnoses or inappropriate investigations. Interestingly, an understanding of these artifacts can be used to diagnose and quantify cyclotorsion of the eyes, which was reported in a case of skew deviation from MS (65). It is important to note that there are differences in the standard measurements obtained by the different commercially available OCT devices, including thickness of the central macula and RNFL (66). For example, eyes with no light perception from chronic optic neuropathy have been shown to have an average RNFL thickness of 45.42 mm with time-domain OCT and 34.18 mm with spectral-domain OCT (67,68). These differences are important to recognize when comparing the results from different OCT machines. In summary, OCT is an evolving technology with faster scans and higher resolution being developed. Enhanced depth imaging and swept-source OCT allow imaging of the deeper layers of the eye. OCT angiography will allow better visualization of the capillaries and an approximation of ocular flow. These advances will ultimately provide us with Chen: J Neuro-Ophthalmol 2018; 38: e5-e8 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Virtual Issue a better understanding of disease pathogenesis and allow us to be better clinicians. REFERENCES 1. Trick GL, Calotti FY, Skarf B. Advances in imaging of the optic disc and retinal nerve fiber layer. J Neuroophthalmol. 2006;26:284-295. 2. Sergott RC, Balcer LJ. The latest on optical coherence tomography. J Neuroophthalmol. 2014;34(suppl):S1-S2. 3. Savino PJ. Evaluation of the retinal nerve fiber layer: descriptive or predictive? J Neuroophthalmol. 2009;29:245-249. 4. Costello FE. Optical coherence tomography technologies: which machine do you want to own? J Neuroophthalmol. 2014;34(suppl):S3-S9. 5. Kardon RH. Role of the macular optical coherence tomography scan in neuro-ophthalmology. J Neuroophthalmol. 2011;31:353-361. 6. Lam BL. Retinal ganglion cell thickness to assess the optic nerve. J Neuroophthalmol. 2015;35:107-108. 7. Sergott RC. Retinal segmentation using multicolor laser imaging. J Neuroophthalmol. 2014;34(suppl):S24-S28. 8. Kardon R. Optical coherence tomography in papilledema: what am I missing? J Neuroophthalmol. 2014;34(suppl):S10-S17. 9. Goldhagen BE, Bhatti MT, Srinivasan PP, Chiu SJ, Farsiu S, El-Dairi MA. Retinal atrophy in eyes with resolved papilledema detected by optical coherence tomography. J Neuroophthalmol. 2015;35:122-126. 10. Rebolleda G, de Dompablo E, Munoz-Negrete FJ. Ganglion cell layer analysis unmasks axonal loss in anterior optic neuritis. J Neuroophthalmol. 2015;35:165-167. 11. Akbari M, Abdi P, Fard MA, Afzali M, Ameri A, YazdaniAbyaneh A, Mohammadi M, Moghimi S. Retinal ganglion cell loss precedes retinal nerve fiber thinning in nonarteritic anterior ischemic optic neuropathy. J Neuroophthalmol. 2016;36:141-146. 12. Kupersmith MJ. Optical imaging of the optic nerve: beyond demonstration of retinal nerve fiber layer loss. J Neuroophthalmol. 2015;35:210-219. 13. Bruce BB. Noninvasive assessment of cerebrospinal fluid pressure. J Neuroophthalmol. 2014;34:288-294. 14. Sibony P, Strachovsky M, Honkanen R, Kupersmith MJ. Optical coherence tomography shape analysis of the peripapillary retinal pigment epithelium layer in presumed optic nerve sheath meningiomas. J Neuroophthalmol. 2014;34:130-136. 15. McCulley TJ, Chang JR, Piluek WJ. Intracranial pressure and glaucoma. J Neuroophthalmol 2015;35(suppl 1):S38-S44. 16. Fraser CL, White AJ, Plant GT, Martin KR. Optic nerve cupping and the neuro-ophthalmologist. J Neuroophthalmol. 2013;33:377-389. 17. Burgoyne C. The morphological difference between glaucoma and other optic neuropathies. J Neuroophthalmol. 2015;35 (suppl 1):S8-S21. 18. Danesh-Meyer HV, Moster ML. At the crossroads of glaucoma and neuro-ophthalmology. J Neuroophthalmol. 2015;35(suppl 1):S1-S3. 19. Pruzan NL, Myers JS. Phenotypic differences in normal vs high tension glaucoma. J Neuroophthalmol. 2015;35 (suppl 1):S4-S7. 20. Sarac O, Tasci YY, Gurdal C, Can I. Differentiation of optic disc edema from optic nerve head drusen with spectral-domain optical coherence tomography. J Neuroophthalmol. 2012;32:207-211. 21. Silverman AL, Tatham AJ, Medeiros FA, Weinreb RN. Assessment of optic nerve head drusen using enhanced depth imaging and swept source optical coherence tomography. J Neuroophthalmol. 2014;34:198-205. 22. Malmqvist L, Wegener M, Sander BA, Hamann S. Peripapillary retinal nerve fiber layer thickness corresponds to drusen location and extent of visual field defects in superficial and buried optic disc drusen. J Neuroophthalmol. 2016;36:41-45. 23. Vieira LM, Silva NF, Dias dos Santos AM, dos Anjos RS, Pinto LA, Vicente AR, Borges BI, Ferreira JP, Amado DM, da Cunha JP. Chen: J Neuro-Ophthalmol 2018; 38: e5-e8 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. Retinal ganglion cell layer analysis by optical coherence tomography in toxic and nutritional optic neuropathy. J Neuroophthalmol. 2015;35:242-245. Epstein AE, Cavuoto KM, Chang TC. Utilizing optical coherence tomography in diagnosing a unique presentation of chiasmal hypoplasia variant of septo-optic dysplasia. J Neuroophthalmol. 2014;34:103-104. Tieger MGH, Thomas R III, Ho J, Erlich-Malona NK, Vuong LN, Athappilly GK, Mendoza-Santiesteban CE. Ganglion cell complex loss in chiasmal compression by brain tumors. J Neuroophthalmol. 2017;37:7-12. Jeong AR, Kim EY, Kim NR. Preferential ganglion cell loss in the nasal hemiretina in patients with pituitary tumor. J Neuroophthalmol. 2016;36:152-155. Vislisel JM, Chen JJ, Kardon RH. Localizing the lesion in Foster Kennedy syndrome from hemiretinal atrophy at the macula. J Neuroophthalmol. 2014;34:422-425. Romero RS, Gutierrez I, Wang E, Reder AT, Bhatti MT, Bernard JT, Javed A. Homonymous hemimacular thinning: a unique presentation of optic tract injury in neuromyelitis optica. J Neuroophthalmol. 2012;32:150-153. Meier PG, Maeder P, Kardon RH, Borruat FX. Homonymous ganglion cell layer thinning after isolated occipital lesion: macular OCT demonstrates transsynaptic retrograde retinal degeneration. J Neuroophthalmol. 2015;35:112-116. Mitchell JR, Oliveira C, Tsiouris AJ, Dinkin MJ. Corresponding ganglion cell atrophy in patients with postgeniculate homonymous visual field loss. J Neuroophthalmol. 2015;35:353-359. Iseri PK, Altinas O, Tokay T, Yuksel N. Relationship between cognitive impairment and retinal morphological and visual functional abnormalities in Alzheimer disease. J Neuroophthalmol. 2006;26:18-24. Adam CR, Shrier E, Ding Y, Glazman S, Bodis-Wollner I. Correlation of inner retinal thickness evaluated by spectraldomain optical coherence tomography and contrast sensitivity in Parkinson disease. J Neuroophthalmol. 2013;33:137-142. Kirbas S, Turkyilmaz K, Tufekci A, Durmus M. Retinal nerve fiber layer thickness in Parkinson disease. J Neuroophthalmol. 2013;33:62-65. Sari ES, Koc R, Yazici A, Sahin G, Ermis SS. Ganglion cell-inner plexiform layer thickness in patients with Parkinson disease and association with disease severity and duration. J Neuroophthalmol. 2015;35:117-121. Kaur M, Saxena R, Singh D, Behari M, Sharma P, Menon V. Correlation between structural and functional retinal changes in Parkinson disease. J Neuroophthalmol. 2015;35:254-258. Balcer LJ. Clinical trials to clinical use: using vision as a model for multiple sclerosis and beyond. J Neuroophthalmol. 2014;34(suppl):S18-S23. Winges KM, Werner JS, Harvey DJ, Cello KE, Durbin MK, Balcer LJ, Calabresi PA, Keltner JL. Baseline retinal nerve fiber layer thickness and macular volume quantified by OCT in the North American phase 3 fingolimod trial for relapsing-remitting multiple sclerosis. J Neuroophthalmol. 2013;33:322-329. Galetta KM, Graves J, Talman LS, Lile DJ, Frohman EM, Calabresi PA, Galetta SL, Balcer LJ. Visual pathway axonal loss in benign multiple sclerosis: a longitudinal study. J Neuroophthalmol. 2012;32:116-123. Sakai RE, Feller DJ, Galetta KM, Galetta SL, Balcer LJ. Vision in multiple sclerosis: the story, structure-function correlations, and models for neuroprotection. J Neuroophthalmol. 2011;31:362-373. Balcer LJ, Galetta SL. OCT and NMO: are there methods to our madness? J Neuroophthalmol. 2013;33:209-212. Lange AP, Sadjadi R, Zhu F, Alkabie S, Costello F, Traboulsee AL. Spectral-domain optical coherence tomography of retinal nerve fiber layer thickness in NMO patients. J Neuroophthalmol. 2013;33:213-219. Davies EC, Galetta KM, Sackel DJ, Talman LS, Frohman EM, Calabresi PA, Galetta SL, Balcer LJ. Retinal ganglion cell layer volumetric assessment by spectral-domain optical coherence tomography in multiple sclerosis: application of a high- e7 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Virtual Issue 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. e8 precision manual estimation technique. J Neuroophthalmol. 2011;31:260-264. Morrow MJ, Wingerchuk D. Neuromyelitis optica. J Neuroophthalmol. 2012;32:154-166. Bichuetti DB, de Camargo AS, Falcao AB, Goncalves FF, Tavares IM, de Oliveira EM. The retinal nerve fiber layer of patients with neuromyelitis optica and chronic relapsing optic neuritis is more severely damaged than patients with multiple sclerosis. J Neuroophthalmol. 2013;33:220-224. Costello F, Van Stavern GP. Should optical coherence tomography be used to manage patients with multiple sclerosis? J Neuroophthalmol. 2012;32:363-371. Abalo-Lojo JM, Limeres CC, Gomez MA, Baleato-Gonzalez S, Cadarso-Suarez C, Capeans-Tome C, Gonzalez F. Retinal nerve fiber layer thickness, brain atrophy, and disability in multiple sclerosis patients. J Neuroophthalmol. 2014;34:23-28. Manogaran P, Traboulsee AL, Lange AP. Longitudinal study of retinal nerve fiber layer thickness and macular volume in patients with neuromyelitis optica spectrum disorder. J Neuroophthalmol. 2016;36:363-368. Brody J, Hellmann MA, Marignier R, Lotan I, Stiebel-Kalish H. Neuromyelitis optica spectrum disorder: disease course and long-term visual outcome. J Neuroophthalmol. 2016;36:356-362. Beck RW. The idiopathic intracranial hypertension treatment trial: a long-time coming but worth the wait. J Neuroophthalmol. 2016;36:1-3. Friedman DI, McDermott MP, Kieburtz K, Kupersmith M, Stoutenburg A, Keltner JL, Feldon SE, Schron E, Corbett JJ, Wall M. The idiopathic intracranial hypertension treatment trial: design considerations and methods. J Neuroophthalmol. 2014;34:107-117. Wall M. Idiopathic intracranial hypertension and the idiopathic intracranial hypertension treatment trial. J Neuroophthalmol. 2013;33:1-3. Dinkin MJ, Patsalides A. Venous sinus stenting in idiopathic intracranial hypertension: results of a prospective trial. J Neuroophthalmol. [published ahead of print August 23, 2016] doi: 10.1097/WNO.0000000000000426. Kupersmith MJ, Miller NR. A nonarteritic anterior ischemic optic neuropathy clinical trial: an industry and NORDIC collaboration. J Neuroophthalmol. 2016;36:235-237. Stewart MW, Brazis PW, Barrett KM, Eidelman BH, Mendez JC. Optical coherence tomography in a case of bilateral neuroretinitis. J Neuroophthalmol. 2005;25:131-133. Kitamei H, Suzuki Y, Takahashi M, Katsuta S, Kato H, Yokoi M, Kase M. Retinal angiography and optical coherence tomography disclose focal optic disc vascular leakage and lipid-rich fluid accumulation within the retina in a patient with 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. leber idiopathic stellate neuroretinitis. J Neuroophthalmol. 2009;29:203-207. Mader TH, Gibson CR, Pass AF, Lee AG, Killer HE, Hansen HC, Dervay JP, Barratt MR, Tarver WJ, Sargsyan AE, Kramer LA, Riascos R, Bedi DG, Pettit DR. Optic disc edema in an astronaut after repeat long-duration space flight. J Neuroophthalmol. 2013;33:249-255. Lee AG, Tarver WJ, Mader TH, Gibson CR, Hart SF, Otto CA. Neuro-ophthalmology of space flight. J Neuroophthalmol. 2016;36:85-91. Dag E, Ornek N, Ornek K, Erbahceci-Timur IE. Optical coherence tomography and visual field findings in patients with Friedreich ataxia. J Neuroophthalmol. 2014;34:118-121. Leavitt JA, Singer W, Brown WL, Pulido JS, Brodsky MC. Retinal and pontine striations: neurodiagnostic signs of autosomal recessive spastic ataxia of Charlevoix-Saguenay. J Neuroophthalmol. 2014;34:369-371. Manrique RK, Noval S, Aguilar-Amat MJ, Arpa J, Rosa I, Contreras I. Ophthalmic features of spinocerebellar ataxia type 7. J Neuroophthalmol. 2009;29:174-179. Han J, Kim do W, Lee CH, Han SH. Optic atrophy in a patient with atypical pantothenate kinase-associated neurodegeneration. J Neuroophthalmol. 2016;36:182-186. Lebranchu P, Le Meur G, Magot A, David A, Verny C, Weber M, Milea D. Maculopathy and spinocerebellar ataxia type 1: a new association? J Neuroophthalmol. 2013;33:225-231. Lessell S. Pitfalls in imaging. J Neuroophthalmol. 2011;31:101-102. Chen JJ, Kardon RH. Avoiding clinical misinterpretation and artifacts of optical coherence tomography analysis of the optic nerve, retinal nerve fiber layer, and ganglion cell layer. J Neuroophthalmol. 2016;36:417-438. Chen JJ, Kardon RH, Longmuir RA. Diagnostic features of retinal nerve fiber layer rotation in skew deviation using optical coherence tomography. J Neuroophthalmol. 2014;34:389-392. Watson GM, Keltner JL, Chin EK, Harvey D, Nguyen A, Park SS. Comparison of retinal nerve fiber layer and central macular thickness measurements among five different optical coherence tomography instruments in patients with multiple sclerosis and optic neuritis. J Neuroophthalmol. 2011;31:110-116. Chan CK, Miller NR. Peripapillary nerve fiber layer thickness measured by optical coherence tomography in patients with no light perception from long-standing nonglaucomatous optic neuropathies. J Neuroophthalmol. 2007;27:176-179. Groth SL, Harrison A, Grajewski AL, Lee MS. Retinal nerve fiber layer thickness using spectral-domain optical coherence tomography in patients with no light perception secondary to optic atrophy. J Neuroophthalmol. 2013;33:37-39. Chen: J Neuro-Ophthalmol 2018; 38: e5-e8 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.