The Ocular Pathology of Terson s Syndrome

Transcription

1 The Ocular Pathology of Terson s Syndrome Fang Ko, MD, David L. Knox, MD Purpose: To improve understanding of vision loss and clinical findings, we studied gross and microscopic pathology of retinas and optic nerves of individuals with Terson s syndrome. Design: Retrospective case series with clinicopathologic correlation. Participants: We included 109 deceased individuals with Terson s syndrome. Methods: Histologic sections and gross photographs from 109 cases of Terson s Syndrome, accessed from 1955 to 1992 at the Wm R. Green Laboratory of Ocular Pathology, were studied and photographed; a representative case is described in detail. Main Outcome Measures: Abnormalities in retina and optic nerve. Results: s occur in vitreous, subhyaloid, sub-internal limiting membrane (ILM), intraretinal, and subretinal spaces, in association with macular holes, retinal detachments, and optic neuropathy. Subhyaloid hemorrhages have diffuse morphology, whereas sub-ilm are well-demarcated. Continuous and noncontinuous blood occurs along optic nerves, within nerve sheaths, and in the subdural and subarachnoid spaces. Conclusions: Blood occurring in various layers and locations of the retina, particularly the macula, causes various complications that influence clinical management and visual outcome. Morphology differentiates subhyaloid from sub-ilm hemorrhage. Patterns of hemorrhages of optic nerve contribute to understanding mechanisms of Terson s syndrome. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Ophthalmology 2010;117: by the American Academy of Ophthalmology. Terson first reported associations between intracranial hemorrhage and vitreous hemorrhage in Since then, Terson s syndrome has been defined as vitreous or retinal hemorrhage in the presence of intracranial hemorrhage, occurring in 12.5% to 40% of individuals. 2 6 It is believed that ruptured intracranial aneurysm or head trauma rapidly increases the intracranial pressure. 3,5 This pressure is transmitted through the optic nerve sheath and veins to the optic nerve head and retina, causing rupture of thin capillary walls. 3,5 Reported complications of Terson s syndrome include visual loss, 7 macular holes, 8 epiretinal membrane formation, 9,10 retinal folds, 10,11 proliferative vitreoretinopathy, 12,13 and retinal detachment. 13 It has been suggested that these complications are the result of proliferation of glial and retinal pigment epithelial elements capable of causing retinal distortion and fibrotic adhesions. 8 Reports of the pathology of eyes with Terson s syndrome are limited. Some reports describe epiretinal membranes. 14 Others show blood dissecting between the internal limiting membrane (ILM) and underlying Müller cell end plates. 15 One case report demonstrated preretinal, sub-ilm, intraretinal, and optic nerve sheath hemorrhage. 16 The present report describes 1 representative case, analyzes 30 selected eyes from 16 individuals, and presents photographs of characteristic pathology seen in the vitreous, retina, and optic nerves of eyes with Terson s syndrome. Materials and Methods Indices of histopathology and photographic collections of cases diagnosed as Terson s syndrome in the Wm R. Green Laboratory of Ocular Pathology were searched, retrieved, studied, and selected as emblematic of common features. Thirty-nine cases were based on autopsies from The Johns Hopkins Hospital, Hopkins Bayview Hospital, or Greater Baltimore Medical Center. Fifty-eight cases were acquired from Maryland, Florida, Washington, Delaware, West Virginia, or international Eye Banks. Histologic sections were stained with hematoxylin and eosin or Verhoeff-Van Gieson. Twelve cases were based on histopathologic sections prepared by Richard Lindenberg, MD, a neuropathologist at the Maryland Medical Examiners Office, who donated his collection of ocular tissues to the Wm R. Green Laboratory. These sections were prepared by unroofing optic canals to study long sections of whole nerves, stained with iron stain or Verhoeff-Van Gieson. The location and severity of tissue deposition of blood was the defining characteristic in this study. The eyes of all individuals were classified as either trauma or primary intracranial hemorrhage and their ages tabulated (Fig 1). Informed consent was not required because individuals were deceased. This work is compliant with Health Insurance Portability 2010 by the American Academy of Ophthalmology ISSN /10/$ see front matter Published by Elsevier Inc. doi: /j.ophtha

2 Ophthalmology Volume 117, Number 7, July 2010 Figure 1. Age distribution of patients. The 109 patients ranged from 3 months to 90 years old, with a mean of 47.3 years, median of 51.0 years, and standard deviation (SD) of 21.2 years. The mean age among patients with trauma-related Terson s syndrome was 28.3 years old (median, 23.5; SD, 22.6), and the mean among with intracranial hemorrhage as the inciting event was 56.1 years (median, 57.0; SD, 13.8). Data were not available (NA) for 6 patients. and Accountability Act; all possible individual identifiers have been removed. Institutional Review Board of The Johns Hopkins Medical Institutions, Baltimore, Maryland, decided approval was not required for this study. This research adhered to the tenets of the Declaration of Helsinki. Results Individuals ranged from 3 months to 90 years old, with a mean age of 47.3 years among all individuals, 28.3 years among trauma-related cases, and 56.1 years among those with vasculogenic intracranial hemorrhage. Of the 4 individuals 5 years old, 3 died in motor vehicle accidents and 1 died of intracranial hemorrhage of unknown etiology. Figure 1 shows age distribution of the 109 individuals studied, where Terson s syndrome was caused by trauma, intracranial hemorrhage, or unknown. Thirty eyes from 16 individuals were randomly selected from 109 cases to be specially examined microscopically. Table 1 describes the age, gender, cause of death, estimated number of days between onset of Terson s syndrome and death, and time between death and autopsy. Ten of the 16 individuals were female. Causes of death include trauma (fall, motor vehicle accident, gunshot) or subarachnoid hemorrhage from ruptured intracranial aneurysm or hypertension. All cases involved intracranial hemorrhage. One case (Table 1, number 13) was notable for Marfan s syndrome. Ten individuals died within 2 days of onset of Terson s syndrome, 3 individuals died after 3 to 5 days of onset, and in 3, the duration was unknown. The following representative case (Table 1, number 14) is described. A 40-year-old woman with a history of hypertension presented with sudden onset headache on March 5, Computed tomography at that time was unremarkable. Over the ensuing 2 months, she experienced intermittent headaches. On May 3, 1997, she noticed dizziness with her headaches. On May 10, 1997, she was found unresponsive at home. Repeat computed tomography revealed an intraparenchymal hematoma of the left frontal lobe and hemorrhage into the left lateral ventricle; no significant midline shift or herniation was noted. After progressive worsening of her Glasgow Coma Score, an intraventricular catheter was placed. Subarachnoid hemorrhage with associated cerebral edema caused mass effect and uncal herniation. The individual rapidly developed progressive encephalopathy and died on May 11, In hospital, it was observed that the right pupil did not react to direct stimulation. Ocular fundoscopy was not reported. Postmortem examination on May 12, 1997, revealed a 7-mm berry aneurysm of the left anterior communicating artery with associated hematoma, subarachnoid hemorrhage, and extensive cerebral edema. The left frontal cortex contained a 2.5-cm hematoma. There was diffuse subarachnoid hemorrhage. The mid- 3 Figure 2. Right eye of patient 14. in the outer plexiform layer (OPL) of the retina (stain: hematoxylin and eosin, original magnification, 4). GCL ganglion cell layer; ILM internal limiting membrane; IPL inner plexiform layer; ONL outer nuclear layer; R&C rods and cones. Figure 3. Left eye of patient 14. A, Gross photo of dome-shaped, dense, sharply edged hemorrhage. B, Histopathology of the dome-shaped hemorrhage in cross section beneath the internal limiting membrane (ILM; arrowhead), with hemorrhage in anterior retina (arrow; stain: hematoxylin and eosin; original magnification, 10). C and D, Origins of detached ILM from anterior retina (stain: hematoxylin and eosin; original magnification, 20). Figure 4. Vitreous, subhyaloid, and sub-internal limiting membrane (ILM) hemorrhages. A, Vitreous (arrow) and sub-ilm hemorrhage (arrowhead; stain: hematoxylin and eosin; original magnification, 20). B, Subhyaloid (thin arrow) and sub-ilm hemorrhage (arrowhead), with retinal hemorrhages in ganglion cell, bipolar cell, and outer plexiform layers (stain: hematoxylin and eosin; original magnification, 10). C, Gross photo of subhyaloid hemorrhage with diffuse appearance and irregular border. Figure 5. Retinal hemorrhages. A, Retinal hemorrhages in bipolar cell and outer plexiform layers (OPL), and rods and cones (stain: hematoxylin and eosin; original magnification, 4). B, Blood in anterior retina, ganglion cell, bipolar cell, OPL, and subretinal space (stain: hematoxylin and eosin; original magnification, 10). C, Distended retinal veins in an eye with hemorrhage in sub-ilm (ILM is detached and not visible in this image), ganglion cell, bipolar cell, and OPL (stain: hematoxylin and eosin; original magnification, 10x). GCL ganglion cell layer; ILM internal limiting membrane; IPL inner plexiform layer; ONL outer nuclear layer; R&C rods and cones. Figure 6. Macular hemorrhage. Macula has hemorrhage in outer plexiform layer (OPL), and rods and cones (stain: hematoxylin and eosin; original magnification, 10). GCL ganglion cell layer; ILM internal limiting membrane; IPL inner plexiform layer; ONL outer nuclear layer; R&C rods and cones. Figure 7. Macular hole. Macular hole with hemorrhage in subhyaloid space, ganglion cell layer, inner nuclear layer, outer plexiform layer (OPL), and subretinal space (stain: hematoxylin and eosin; original magnification, 4). GCL ganglion cell layer; ILM internal limiting membrane; IPL inner plexiform layer; ONL outer nuclear layer; R&C rods and cones. 1424

3 Ko and Knox 䡠 Ocular Pathology of Terson s Syndrome 1425

4 Case Age/Gender Cause of Death Ophthalmology Volume 117, Number 7, July 2010 Table 1. Clinical Setting of 16 Patients with Terson s Syndrome Estimated No. of Days from Onset of Terson s until Death Time between Death and Autopsy (hours) 1 90/Female Fall, subdural hematoma /Female Intracranial bleeding /Male Subarachnoid hemorrhage, cardiac arrest N/A 2 4 7/Female MVA /Male Gunshot wound to head /Male Cerebral hemorrhage /Female CVA N/A /Female Subarachnoid hemorrhage N/A /Female Seizures and hydrocephalus secondary to ruptured intracranial aneurysm 10 68/Female Subarachnoid hemorrhage (history of HTN, sudden onset Same day 0.5 of emesis, collapsed, and pronounced brain dead upon arrival to hospital) 11 34/Female Subarachnoid and intracranial hemorrhage /Male Massive cerebral bleed (patient was well until his wife 1 8 found him prone on bathroom floor) 13 37/Female Subarachnoid hemorrhage of posterior fossa, intradural 4 24 hemorrhage of spinal cord, Marfan syndrome 14 40/Female Ruptured berry aneurysm of left anterior communicating 1 24 cerebral artery 15 60/Male Refractory intracranial bleed /Male Intracranial hemorrhage of right cerebral hemisphere with rupture through 1 15 CVA cerebral vascular accident; HA headache; HTN hypertension; MVA motor vehicle accident; N/A not available. brain, pons, and ventricular system showed diffuse, small areas of hemorrhage. Grossly, the right eye showed subconjunctival hemorrhage (4 2 mm) at the superotemporal limbus and 3 well-demarcated, dome-shaped peripapillary retinal hemorrhages ( mm in diameter). No vitreous hemorrhage was noted. Microscopic examination revealed 2 areas of hemorrhage in the outer plexiform layer (OPL), one in the temporal aspect of the macula, the other 1.5 mm anterior to the optic nerve. Figure 2 demonstrates outer plexiform macular hemorrhage. The optic nerve was remarkable for crush artifact. Additional hemorrhages were seen in the subarachnoid space, the subdural space, and within the dural sheath of the optic nerve. The left eye grossly showed subconjunctival hemorrhage ( mm) at the temporal limbus, a dome-shaped sub-ilm hemorrhage with raised edges inferior and temporal to the optic disc (Fig 3A), and a retinal hemorrhage (1 mm in diameter) inferior and nasal to the optic disc. Microscopically, a large hemorrhage (9 mm in diameter) was present beneath ILM at the macula. was also detected in the inner nuclear layer, OPL, and beneath the retina. Figures 3B D demonstrate hemorrhages beneath the ILM, elevation of adjacent ILM, points of detachment of ILM from anterior retina, and compression of the retina with attenuation of the thickness of the outer nuclear cell layer. The optic nerve showed subdural hemorrhage extending into the inner 50% of the dural sheath. The range of pathology observed among the 30 specifically studied eyes is summarized in Table 2 (available online at Vitreous hemorrhage was present in 11 eyes (Fig 4A) and diffuse subhyaloid hemorrhage was present in 10 eyes (Fig 4B). Intraretinal hemorrhage was present in all eyes: 23 eyes had well-demarcated, dome-shaped hemorrhage beneath the ILM (Fig 4B C), 16 eyes had blood in the ganglion cell layer (Fig 5), 19 eyes had hemorrhage in bipolar cell layer (Fig 5), 20 eyes had hemorrhage in the OPL (Fig 5), 9 eyes had hemorrhage in outer nuclear layer (Fig 6), and 4 eyes had hemorrhage of the rods and cones (Figs 6 and 7). Subretinal hemorrhage was seen in 14 eyes (Figs 5B and 7). Figure 7 demonstrates infiltration, distension, and rupture of the macula from an individual who died within 2 days of intracranial hemorrhage. Notably, no eyes had hemorrhage in the inner plexiform layer (IPL). The range of histopathology apparent in optic nerves is summarized in Table 3 (available online at A crush artifact (Fig 8) was seen in the optic nerves of 14 eyes. 3 Figure 8. Crush artifact and optic nerve hemorrhage. Optic nerve in cross section with (A) diffuse distribution of crush artifact (stain: hematoxylin and eosin; original magnification, 3) and (B) hemorrhage within the optic nerve sheath, subdural space, and subarachnoid space (stain: hematoxylin and eosin; original magnification, 3). Figure 9. Optic nerve hemorrhage. Optic nerve hemorrhages in cross section (A) in subdural space (stain: hematoxylin and eosin; original magnification, 4); (B and C) in subdural and subarachnoid space with varying levels of density (stain: hematoxylin and eosin; original magnification, 20). D, Subarachnoid hemorrhage in longitudinal section of optic nerve (stain: hematoxylin and eosin; original magnification, 3). Figure 10. Two types of optic nerve hemorrhage. (A) Multifocal discrete optic nerve hemorrhage (stain: iron stain; original magnification, 1) with (B) higher magnification of distended retinal veins in the same eye (stain: iron stain; original magnification, 10). C, Continuous optic nerve hemorrhage (stain: Verhoeff-Van Gieson; original magnification, 1) with optic chiasm (arrow; stain: Verhoeff-Van Gieson; original magnification, 4). 1426

5 Ko and Knox 䡠 Ocular Pathology of Terson s Syndrome 1427

6 Ophthalmology Volume 117, Number 7, July 2010 was present in the dural sheaths of 9 eyes, in the subdural spaces of 19 eyes, in the subarachnoid spaces of 20 eyes, and within the pia mater of 2 eyes (Fig 9). Figure 10A C from the Lindenberg collection shows optic nerve hemorrhages from 2 individuals who died after trauma. Figure 10A demonstrates focal dural and subdural hemorrhage in midorbital optic nerve, with no evidence of extensions from intracranial blood along optic nerve canal. Distended anterior retinal veins can be seen in this eye (Fig 10B). Figure 10C demonstrates severe subdural blood from the optic chiasm, along the optic canal, to the optic nerve scleral junction. Discussion Terson s syndrome has been reported to cause epiretinal membranes, retinal folds, proliferative vitreoretinopathy, retinal detachment, and macular holes Our histopathologic analysis was undertaken to increase understanding of mechanisms which threaten vision. As shown in Figure 1, our study found a wide range of individual ages. The elderly mainly died of vasculogenic intracranial hemorrhages; younger individuals largely died of trauma-related causes. Vitreous hemorrhage (Fig 4A) in the visual axis obviously reduces visual acuity. Figure 4B demonstrates a thin layer of hemorrhage overlying retina. Yokoi et al 9 proposed that vitreous hemorrhage breaks down the ILM, causing glial cell migration and proliferation into the vitreous cavity and epiretinal membrane formation. 9 This possibility provides an argument for early, operative removal of blood. Previous authors have attempted to distinguish between subhyaloid and sub-ilm hemorrhages. 15,17 We found that subhyaloid hemorrhages are diffuse, irregularly edged, and vary in density (Fig 4C), whereas sub- ILM hematomas are well-demarcated and dome shaped (Fig 3A, B). Both subhyaloid and sub-ilm hemorrhages can be present in the same area (Fig 4B). This corroborates a previously reported double ring sign caused by concurrent subhyaloid and sub-ilm hemorrhage. 18 Figures 3C D show points at which ILM detaches from underlying retina. Hematoma beneath the ILM can cause elevation of the membrane, explaining the macular ring 18 reported by Sadeh et al 19 ; as the sub-ilm hemorrhage contracts and serum is absorbed, the remaining ILM wrinkles and is seen as a folded, reflective surface. Blood may elevate retina, causing retinal folds, proliferative vitreoretinopathy, and retinal detachment (Figs 5 and 6). In some individuals, decreased visual acuity persists after surgery. 4,20,21 Blood at various layers of the retina (Fig 5), particularly at the macula (Fig 6), may explain the long-term loss of visual acuity. Although hemorrhage was seen throughout the retina and subretinal space, it was not found in the IPL of any eye (Figs 2A, 3B, C, 4B, 5, 6 and 7). Even when there was massive hemorrhage throughout the retina, the IPL was spared. This implies that the IPL is a layer of decreased vascularity and vulnerability. Disruption of retina by hemorrhage caused macular hole in an individual who died within 2 days of onset of Terson s syndrome (Fig 7). There was no apparent vitreoretinal traction, the prevailing mechanism proposed by Gass. 22 In this case, there was no clinical information of prior macular disease. The obvious traumatic disruption of the retina is consistent with blood dissecting from ruptured vessels and entering the retinal layers and subretinal space to weaken and disrupt the macula, resulting in a macular hole. Development of a hemorrhage-induced macular hole within 2 days argues for early evaluation of the retina in clinically stable individuals. of the optic nerve sheath is a frequent complication of Terson s syndrome 23 ; in this study, it occurred within the dural sheath, subdural space, subarachnoid space, or pia mater (Fig 9). Figure 10A demonstrates multifocal optic nerve hemorrhages. In 1943, Ballantyne 24 proposed and presented evidence that intraocular and subdural optic nerve hemorrhages of Terson s syndrome were locally multifocal and not extensions of intracranial blood. According to this explanation, multiple foci of hemorrhage can cause continuous blood along optic nerve canal from chiasm to sclera (Fig 10B). Although it is possible that there are 2 mechanisms for Terson s syndrome, we believe multifocal bleeding is the most common. This study is limited in that eyes used for histopathologic analysis were necessarily acquired from deceased individuals, possibly describing a range of disease that is more severe than what is usually seen clinically. Future studies could determine whether the range of histopathologic findings correlates with severity of disease by incorporating orbital ultrasound, ocular coherence tomography, and magnetic resonance imaging. From this study, we see a need for clinicians to be more aggressive in early evaluation of individuals with head trauma and subarachnoid hemorrhage from ruptured intracranial vessels. Current recommendations in literature suggest 3 to 6 months of observation after the acute event, followed by vitrectomy if there is no improvement in visual acuity. 6,25 28 This report demonstrates a range of pathology that occurs within 1 week of onset of Terson s syndrome, including vision-threatening findings of vitreous hemorrhage, retinal hemorrhage, foveal damage, and macular hole. Our study suggests that earlier definition of the extent and location of bleeding, before 3 months, can optimize clinical management. Although it is not possible to obtain histopathology without damaging eyes of living individuals, ultrasound, magnetic resonance imaging, and ocular coherence tomography can bridge the gap between clinical and pathologic findings. These diagnostic studies, together with knowledge of the range of disease that occurs in Terson s syndrome demonstrated by our study, may guide clinicians in determining whether earlier surgery may improve clinical outcomes of visual acuity and rehabilitation. 1428

7 Ko and Knox Ocular Pathology of Terson s Syndrome References 1. Terson A. De l hemorrhagie dans le corps vitre au cours de l hemorrhagie cerebrale. Clin Ophthalmol 1900;6: Ness T, Janknecht P, Berghorn C. Frequency of ocular hemorrhages in patients with subarachnoidal hemorrhage. Graefes Arch Clin Exp Ophthalmol 2005;243: Medele RJ, Stummer W, Mueller AJ, et al. Terson s syndrome in subarachnoid hemorrhage and severe brain injury accompanied by acutely raised intracranial pressure. J Neurosurg 1998;88: Kuhn F, Morris R, Witherspoon CD, Mester V. Terson syndrome: results of vitrectomy and the significance of vitreous hemorrhage in patients with subarachnoid hemorrhage. Ophthalmology 1998;105: Pfausler B, Belcl R, Metzler R, et al. Terson s syndrome in spontaneous subarachnoid hemorrhage: a prospective study in 60 consecutive patients. J Neurosurg 1996;85: Fountas KN, Kapsalaki EZ, Lee GP, et al. Terson hemorrhage in individuals suffering aneurysmal subarachnoid hemorrhage: predisposing factors and prognostic significance. J Neurosurg 2008;109: McCarron MO, Alberts MJ, McCarron P. A systematic review of Terson s syndrome: frequency and prognosis after subretinal haemorrhage. J Neurol Neurosurg Psychiatry 2004;75: Rubowitz A, Desai U. Nontraumatic macular holes associated with Terson syndrome. Retina 2006;26: Yokoi M, Kase M, Hyodo T, et al. Epiretinal membrane formation in Terson syndrome. Jpn J Ophthalmol 1997;41: Sharma T, Gopal L, Biswas J, et al. Results of vitrectomy in Terson syndrome. Ophthalmic Surg Lasers 2002;33: Keithahn MA, Bennett SR, Cameron D, Mieler WF. Retinal folds in Terson syndrome. Ophthalmology 1993;100: Ritland JS, Syrdalen P, Eide N, et al. Outcome of vitrectomy in patients with Terson syndrome. Acta Ophthalmol Scand 2002;80: Velikay M, Datlinger P, Stolba U, et al. Retinal detachment with severe proliferative vitreoretinopathy in Terson syndrome. Ophthalmology 1994;101: Garcia-Arumi J, Corcostegui B, Tallada N, Salvador F. Epiretinal membranes in Terson s syndrome: a clinicopathologic study. Retina 1994;14: Friedman SM, Margo CE. Bilateral subinternal limiting membrane hemorrhage with Terson syndrome. Am J Ophthalmol 1997;124: Morris DA, Henkind P. Relationship of intracranial, opticnerve sheath, and retinal hemorrhage. Am J Ophthalmol 1967; 64: Weingeist TA, Goldman EJ, Folk JC, et al. Terson s syndrome: clinicopathologic correlations. Ophthalmology 1986;93: Srinivasan S, Kyle G. Subinternal limiting membrane and subhyaloid haemorrhage in Terson syndrome: the macular double ring sign [letter]. Eye 2006;20: Sadeh AD, Lazar M, Loewenstein A. Macular ring in a patient with Terson s syndrome. Acta Ophthalmol Scand 1999;77: Garweg JG, Koerner F. Outcome indicators for vitrectomy in Terson syndrome. Acta Ophthalmol 2009;87: Schultz PN, Sobol WM, Weingeist TA. Long-term visual outcome in Terson syndrome. Ophthalmology 1991;98: Gass JD. Idiopathic senile macular hole: its early stages and pathogenesis. Arch Ophthalmol 1988;106: Gauntt CD, Sherry RG, Kannan C. Terson syndrome with bilateral optic nerve sheath hemorrhage. J Neuroophthalmol 2007;27: Ballantyne AJ. The ocular manifestations of spontaneous subarachnoid haemorrhage. Br J Ophthalmol 1943;27: Augsten R, Königsdörffer E. Terson syndrome a contribution to the timing of operation for pars plana vitrectomy [in German]. Klin Monatsbl Augenheilkd 2007;224: Biousse V, Mendicino ME, Simon DJ, Newman NJ. The ophthalmology of intracranial vascular abnormalities. Am J Ophthalmol 1998;125: Garfinkle AM, Danys IR, Nicolle DA, et al. Terson s syndrome: a reversible cause of blindness following subarachnoid hemorrhage. J Neurosurg 1992;76: Vanderlinden RG, Chisholm LD. Vitreous hemorrhages and sudden increased intracranial pressure. J Neurosurg 1974;41: Footnotes and Financial Disclosures Originally received: April 22, Final revision: November 18, Accepted: November 18, Available online: March 29, Manuscript no From The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore Maryland. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Correspondence: David L. Knox, MD, The Johns Hopkins Hospital, Woods 275, 601 N Broadway, Baltimore MD daknox@jhmi.edu. 1429

8 Case/Eye Vitreous Table 2. in the Vitreous Cavity, Retina, and Subretinal Space Subhyaloid Ophthalmology Volume 117, Number 7, July 2010 Intraretinal Sub-ILM GCL IPL INL OPL ONL Rods and Cones Subretinal 1OD 1OS 2OD 2OS 3OD 3OS 4OD 4OS 5OD 5OS 6OD 6OS 7OD 8OD 8OS 9OS 10 OD 10 OS 11 OD 11 OS 12 OD 12 OS 13 OD 13 OS 14 OD 14 OS 15 OD 15 OS 16 OD 16 OS GCL ganglion cell layer; ILM internal limiting membrane; IPL inner plexiform layer; OD right eye; ONL outer nuclear layer; OPL outer plexiform layer; OS left eye e1

9 Case/Eye Crush Artifact Ko and Knox Ocular Pathology of Terson s Syndrome Table 3. Histopathology of the Optic Nerve Intrasheath Subdural Subarachnoid within Pia Mater 1OD 1OS 2OD 2OS 3OD 3OS 4OD 4OS 5OD 5OS 6OD 6OS 7OD 8OD 8OS 9 OS N/A 10 OD 10 OS 11 OD 11 OS 12 OD 12 OS 13 OD 13 OS 14 OD 14 OS 15 OD 15 OS 16 OD 16 OS N/A cross-section is not available; OD right eye; OS left eye e2