Correspondence
Leber hereditary optic neuropathy and multiple sclerosis: the mitochondrial connection A 20-year-old white female experienced progressive, painless loss of vision in the left eye over a 3-month period. Before the visual loss, she was healthy and denied any recent illness or neurologic symptoms. She did not take any medications and was a nonsmoker and nondrinker. She had a maternal aunt and 2 maternal great uncles with unexplained visual loss. At her local ophthalmologist’s office, visual acuity was 20/20 OD and 1/200 OS, with a left relative afferent pupillary defect. Slit-lamp examination was noted to be unremarkable. Dilated fundus examination was normal in the right eye and there was optic nerve pallor in the left eye. An orbital and cranial magnetic resonance imaging (MRI) with contrast was negative. Despite treatment with 3 days of intravenous methylprednisolone, vision in the left eye deteriorated to hand motions over the subsequent weeks. Based on her clinical and family history, she underwent genetic testing for Leber hereditary optic neuropathy (LHON), which confirmed a G11778A point mutation. She remained stable for 3 years until she experienced bilateral lower extremity weakness and paraesthesias, which prompted an evaluation by a neurologist. Contrast-enhanced cranial MRI demonstrated scattered periventricular and corpus callosum T2 hyperintense signal abnormalities. Cerebrospinal fluid analysis was normal except for the presence of 9 oligoclonal bands. She was given the diagnosis of multiple sclerosis (MS) and offered treatment with a disease-modifying drug but declined because of her plans to start a family. Three years later, with no intervening health issues, she felt a bandlike sensation around her midabdomen up to her lower breast region and lower extremity weakness. A MRI of the brain and spinal cord revealed progression of the number and size of the cervical spinal cord and brain
lesions (Fig. 1). None of the lesions enhanced after the administration of contrast. She was treated with a 3-day course of oral prednisone and started on once-weekly intramuscular injections of interferon β-1a. A few months later, she experienced painless central blurring of vision in the right eye. Her neurologist considered switching to natalizumab because of the vision loss; however, she was antibody positive for the John Cunningham virus. On her visit to our neuro-ophthalmology clinic, visual acuity was 20/100 OD and hand motions OS. Colour vision was 8/10 OD and no control plate OS. There was a relative afferent pupillary defect OS. Slit-lamp, ocular motility, and cranial nerve examinations were all normal. Funduscopic examination revealed temporal optic nerve pallor of the right eye and diffuse optic nerve pallor in the left eye (Fig. 2). The macula, retinal vessels, and retinal periphery were normal for both eyes. Standard automated perimetry demonstrated a central scotoma with an inferior arcuate defect in the right eye and a dense central scotoma in the left eye (Fig. 3). Optical coherence tomography showed mild superonasal and superotemporal thinning of the retinal nerve fibre layer (RNFL) in the right eye and diffuse RNFL thinning of the left eye (Fig. 4). Because of the absence of eye pain and lack of visual improvement, it was believed the visual loss in the right eye (similar to the left eye) was due to LHON. She returned to her neurologist to consider starting a diseasemodifying drug for MS with the understanding that there was no known effective treatment for the visual loss. The occurrence of LHON-MS, as in this case, is known as Harding syndrome. Given the known prevalence of the mutations causing LHON and of MS, the risk for development of both conditions is about 50 times greater than expected, making it less likely an association by chance alone. More than 90% of patients with LHON harbor 1 of the 3 pathogenic mitochondrial DNA mutations: 11778, 3460, and 14484; when it is associated with an MS-like syndrome, the 11778 LHON mutation is
Fig. 1 — Cranial and spinal magnetic resonance imaging (MRI). There are multiple T2-weighted hyperintense lesions (arrows) in the cervical spinal cord (A). Sagittal (B) and axial (C) fluid-attenuated inversion recovery (FLAIR) images of the brain show multiple high-signal intense lesions (arrows) in the periventricular and corpus callosum regions, characteristic of multiple sclerosis.
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CAN J OPHTHALMOL — VOL. 50, NO. 1, FEBRUARY 2015
Correspondence
Fig. 2 — Colour fundus photographs demonstrate temporal optic nerve pallor with hyperemia OD (A) and diffuse optic nerve pallor OS (B).
most commonly involved.1 The possible link between these 2 conditions may be tied to mitochondria. It has been nearly 150 years since Dr. Jean-Martin Charcot first penned his clinical observations of “sclerose en plaques.”2 MS afflicts more than 2.1 million people worldwide, usually beginning in the prime years of an individual’s life. Patients can present with a myriad of clinical signs and symptoms, including weakness, spasms, gait abnormalities, and vision loss.3 The clinical course of MS is variable, with approximately 85% of patients
demonstrating a relapsing-remitting course, 10% with a primary progressive course, and the remaining with a progressive relapsing course.3 Although the exact pathogenesis of MS remains unknown, it is believed to be a chronic inflammatory demyelination of the central nervous system (CNS) associated with axonal destruction.4 MS has long been considered a T-cell immunological response to myelinassociated antigens. The activation of T cells triggers a proinflammatory cascade of events orchestrated by
Fig. 3 — Standard automated perimetry demonstrates a central scotoma with an inferior arcuate defect OD and a dense central scotoma OS. CAN J OPHTHALMOL — VOL. 50, NO. 1, FEBRUARY 2015
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Correspondence
Fig. 4 — Optical coherence tomography demonstrates mild superonasal and superotemporal thinning of the retinal nerve fibre layer (RNFL) of the right eye and diffuse RNFL thinning of the left eye.
microglia and macrophages—the key players in the acute inflammatory lesions.5 Extensive research has found that the neurodegenerative phase of the disease is not exclusively dependent on inflammation. There is increasing evidence that mitochondria, the site of aerobic respiration and adenosine-50 -triphosphate synthesis within the cell, are crucial organelles for maintenance of axonal integrity in the CNS. For example, mitochondrial dysfunction can lead to catastrophic neurologic disorders such as mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes and myoclonic epilepsy with raggedred fibres.6 In addition, MS has not only been associated with LHON, but another ophthalmic mitochondrial disease: chronic progressive external ophthalmoplegia.7 Tissue injury caused by mitochondrial dysfunction has been shown to be caused by at least 3 different mechanisms8: reactive oxygen species production, energy failure, and apoptosis induction. In the acute MS lesion, axonal degeneration is believed to result from glutamate excitotoxicity9 and increased nitric oxide levels released by macrophages, leading to loss of mitochondrial function, inhibition of aerobic respiration, and production of toxic free radical in demyelinated axons.10 In the chronic MS plaque, studies have shown that loss of myelin and the resultant negative effects on “salutatory conduction” leads to increased energy demand from mitochondria. In myelinated axons within the CNS, more than 90% of
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mitochondria are located within the juxtaparanodal and internodal regions of the axon.11 Altered distribution of voltage-gated channels and increased energy requirements causes increased axoplasmic calcium concentrations, which stimulates proapoptotic pathways within the existing mitochondria.8,12 The fact that small-diameter axons are preferentially lost in MS further implicates mitochondria as a critical player in axonal loss.13 The lack of volume relative to surface area in small-diameter axons correlates to a reduced “energy to ions” ratio, thus making these axons more vulnerable to degeneration.6 Further evidence linking mitochondrial dysfunction to MS has been investigated through electron microscopic evaluation of postmortem tissue, showing decreased numbers of mitochondria and microtubules within demyelinated lesions.14 In addition, studies in experimental autoimmune encephalomyelitis, an animal model of MS, have demonstrated that maintenance of mitochondrial integrity can affect disease progression and axonal survival.15 Abnormal mitochondrial morphology was noted to be the earliest ultrastructural sign of damage, preceding structural changes. Mitochondria are ubiquitous cellular organelles that are vital for the survival of eukaryotic cells. There is an increasing body of evidence that mitochondrial function and response to stress play a significant role in the neurodegenerative process that leads to permanent disability in patients with MS and LHON.16,17 Further insights into
CAN J OPHTHALMOL — VOL. 50, NO. 1, FEBRUARY 2015
Correspondence the molecular mechanisms of MS and LHON will be critical in the development of novel neuroprotective and neuroregenerative therapeutic approaches with the ultimate hope of one day curing these debilitating diseases.18
Disclosure: The authors have no proprietary or commercial interest in any materials discussed in this article. Supported by: This work was supported by an unrestricted departmental grant from Research to Prevent Blindness, Inc.
Varsha Manjunath, M. Tariq Bhatti Duke University Eye Center, Duke University Medical Center, Durham, N.C. Correspondence to: M. Tariq Bhatti, MD: [email protected] REFERENCES 1. Kovacs GG, Hoftberger R, Majtenyi K, et al. Neuropathology of white matter disease in Leber’s hereditary optic neuropathy. Brain. 2005;128:35-41. 2. Lublin F. History of modern multiple sclerosis therapy. J Neurol. 2005;252(Suppl 3):iii3-9. 3. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med. 2000;343:938-52. 4. Trapp BD, Nave KA. Multiple sclerosis: an immune or neurodegenerative disorder? Annu Rev Neurosci. 2008;31:247-69. 5. Huitinga I, van Rooijen N, de Groot CJ, Uitdehaag BM, Dijkstra CD. Suppression of experimental allergic encephalomyelitis in Lewis rats after elimination of macrophages. J Exp Med. 1990;172: 1025-33. 6. Campbell GR, Ohno N, Turnbull DM, Mahad DJ. Mitochondrial changes within axons in multiple sclerosis: an update. Curr Opin Neurol. 2012;25:221-30.
Transient corneal edema circumscribed to the LASIK flap after uneventful cataract surgery Previous studies have shown how LASIK surgery induces long-term changes in the corneal flap,1 the LASIK interface,2 and the residual stromal bed.3 Dawson et al.4 have reported different hydraulic behaviours between stromal bed and LASIK flap in human eye bank corneas, in 2 experimental models of interface fluid syndrome. We present a case of transient corneal edema after cataract surgery, confined to the LASIK flap. This would confirm, in vivo, the different hydraulic behaviour of the LASIK flap compared with the stromal bed and the rest of the cornea. A 58-year-old male was referred to our clinic for cataract surgery in his left eye. Seven years before he had had an uneventful femtosecond LASIK surgery to correct a refractive error of –4.00, –0.75 901 in his left eye with plano result. He had a nuclear cataract, 2530 endothelial cells/mm2, and the central corneal thickness
7. Slee M, Krupa M, Raghupathi R, et al. A novel mitochondrial DNA deletion producing progressive external ophthalmoplegia associated with multiple sclerosis. J Clin Neurosci. 2011;18:1318-24. 8. Lassmann H, van Horssen J. The molecular basis of neurodegeneration in multiple sclerosis. FEBS Lett. 2011;585:3715-23. 9. Kostic M, Zivkovic N, Stojanovic I. Multiple sclerosis and glutamate excitotoxicity. Rev Neurosci. 2013;24:71-88. 10. Lu F, Selak M, O’Connor J, et al. Oxidative damage to mitochondrial DNA and activity of mitochondrial enzymes in chronic active lesions of multiple sclerosis. J Neurol Sci. 2000;177:95-103. 11. Campbell GR, Mahad DJ. Mitochondrial changes associated with demyelination: consequences for axonal integrity. Mitochondrion. 2012;12:173-9. 12. Waxman SG. Axonal conduction and injury in multiple sclerosis: the role of sodium channels. Nat Rev Neurosci. 2006;7:932-41. 13. DeLuca GC, Ebers GC, Esiri MM. Axonal loss in multiple sclerosis: a pathological survey of the corticospinal and sensory tracts. Brain. 2004;127(Pt 5):1009-18. 14. Dutta R, McDonough J, Yin X, et al. Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients. Ann Neurol. 2006;59:478-89. 15. Nikic I, Merkler D, Sorbara C, et al. A reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis. Nat Med. 2011;17:495-9. 16. Su KG, Banker G, Bourdette D, Forte M. Axonal degeneration in multiple sclerosis: the mitochondrial hypothesis. Curr Neurol Neurosci. 2009;Rep 9:411-7. 17. Durastanti V, Monaco A, Caronti B, et al. Mitochondrial genome profile in demyelinating disease. J Neurol Neurophysiol. 2013;5:179. 18. Koilkonda RD, Guy J. Leber’s hereditary optic neuropathy-gene therapy: from benchtop to bedside. J Ophthalmol. 2011;2011: 179412.
Can J Ophthalmol 2015;50:e14–e17 0008-4182/15/$-see front matter & 2015 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcjo.2014.10.018
was 520 μm measured by ultrasonic pachymeter. He had neither signs nor family history of glaucoma. An uneventful phacoemulsification technique was performed, and a monofocal intraocular lens was implanted. The patient was instructed to apply topical antibiotic and steroid drops every 6 hours. On postoperative day 1, the uncorrected distance visual acuity was 20/80. The slit-lamp examination showed corneal edema circumscribed to the LASIK flap (Fig. 1); the underlying residual stromal bed and cornea surrounding the flap limits were clear. The intraocular pressure (IOP) was 25 mm Hg and the lens was correctly positioned in the capsular bag. No fluid was detected in the interface between the flap and the stromal bed with the anterior segment optical coherence tomography (Fig. 2). Topical timolol maleate twice a day and hyperosmotic eye drops 3 times daily were prescribed in addition. One week later, the UCVA improved to 20/25, the flap edema was completely resolved, and IOP was 16 mm Hg. Corneal hydration is determined by factors such as endothelial pump, epithelial barrier, water evaporation,
CAN J OPHTHALMOL — VOL. 50, NO. 1, FEBRUARY 2015
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Leber hereditary optic neuropathy and multiple sclerosis: the mitochondrial connection A 20-year-old white female experienced progressive, painless loss of vision in the left eye over a 3-month period. Before the visual loss, she was healthy and denied any recent illness or neurologic symptoms. She did not take any medications and was a nonsmoker and nondrinker. She had a maternal aunt and 2 maternal great uncles with unexplained visual loss. At her local ophthalmologist’s office, visual acuity was 20/20 OD and 1/200 OS, with a left relative afferent pupillary defect. Slit-lamp examination was noted to be unremarkable. Dilated fundus examination was normal in the right eye and there was optic nerve pallor in the left eye. An orbital and cranial magnetic resonance imaging (MRI) with contrast was negative. Despite treatment with 3 days of intravenous methylprednisolone, vision in the left eye deteriorated to hand motions over the subsequent weeks. Based on her clinical and family history, she underwent genetic testing for Leber hereditary optic neuropathy (LHON), which confirmed a G11778A point mutation. She remained stable for 3 years until she experienced bilateral lower extremity weakness and paraesthesias, which prompted an evaluation by a neurologist. Contrast-enhanced cranial MRI demonstrated scattered periventricular and corpus callosum T2 hyperintense signal abnormalities. Cerebrospinal fluid analysis was normal except for the presence of 9 oligoclonal bands. She was given the diagnosis of multiple sclerosis (MS) and offered treatment with a disease-modifying drug but declined because of her plans to start a family. Three years later, with no intervening health issues, she felt a bandlike sensation around her midabdomen up to her lower breast region and lower extremity weakness. A MRI of the brain and spinal cord revealed progression of the number and size of the cervical spinal cord and brain
lesions (Fig. 1). None of the lesions enhanced after the administration of contrast. She was treated with a 3-day course of oral prednisone and started on once-weekly intramuscular injections of interferon β-1a. A few months later, she experienced painless central blurring of vision in the right eye. Her neurologist considered switching to natalizumab because of the vision loss; however, she was antibody positive for the John Cunningham virus. On her visit to our neuro-ophthalmology clinic, visual acuity was 20/100 OD and hand motions OS. Colour vision was 8/10 OD and no control plate OS. There was a relative afferent pupillary defect OS. Slit-lamp, ocular motility, and cranial nerve examinations were all normal. Funduscopic examination revealed temporal optic nerve pallor of the right eye and diffuse optic nerve pallor in the left eye (Fig. 2). The macula, retinal vessels, and retinal periphery were normal for both eyes. Standard automated perimetry demonstrated a central scotoma with an inferior arcuate defect in the right eye and a dense central scotoma in the left eye (Fig. 3). Optical coherence tomography showed mild superonasal and superotemporal thinning of the retinal nerve fibre layer (RNFL) in the right eye and diffuse RNFL thinning of the left eye (Fig. 4). Because of the absence of eye pain and lack of visual improvement, it was believed the visual loss in the right eye (similar to the left eye) was due to LHON. She returned to her neurologist to consider starting a diseasemodifying drug for MS with the understanding that there was no known effective treatment for the visual loss. The occurrence of LHON-MS, as in this case, is known as Harding syndrome. Given the known prevalence of the mutations causing LHON and of MS, the risk for development of both conditions is about 50 times greater than expected, making it less likely an association by chance alone. More than 90% of patients with LHON harbor 1 of the 3 pathogenic mitochondrial DNA mutations: 11778, 3460, and 14484; when it is associated with an MS-like syndrome, the 11778 LHON mutation is
Fig. 1 — Cranial and spinal magnetic resonance imaging (MRI). There are multiple T2-weighted hyperintense lesions (arrows) in the cervical spinal cord (A). Sagittal (B) and axial (C) fluid-attenuated inversion recovery (FLAIR) images of the brain show multiple high-signal intense lesions (arrows) in the periventricular and corpus callosum regions, characteristic of multiple sclerosis.
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CAN J OPHTHALMOL — VOL. 50, NO. 1, FEBRUARY 2015
Correspondence
Fig. 2 — Colour fundus photographs demonstrate temporal optic nerve pallor with hyperemia OD (A) and diffuse optic nerve pallor OS (B).
most commonly involved.1 The possible link between these 2 conditions may be tied to mitochondria. It has been nearly 150 years since Dr. Jean-Martin Charcot first penned his clinical observations of “sclerose en plaques.”2 MS afflicts more than 2.1 million people worldwide, usually beginning in the prime years of an individual’s life. Patients can present with a myriad of clinical signs and symptoms, including weakness, spasms, gait abnormalities, and vision loss.3 The clinical course of MS is variable, with approximately 85% of patients
demonstrating a relapsing-remitting course, 10% with a primary progressive course, and the remaining with a progressive relapsing course.3 Although the exact pathogenesis of MS remains unknown, it is believed to be a chronic inflammatory demyelination of the central nervous system (CNS) associated with axonal destruction.4 MS has long been considered a T-cell immunological response to myelinassociated antigens. The activation of T cells triggers a proinflammatory cascade of events orchestrated by
Fig. 3 — Standard automated perimetry demonstrates a central scotoma with an inferior arcuate defect OD and a dense central scotoma OS. CAN J OPHTHALMOL — VOL. 50, NO. 1, FEBRUARY 2015
e15
Correspondence
Fig. 4 — Optical coherence tomography demonstrates mild superonasal and superotemporal thinning of the retinal nerve fibre layer (RNFL) of the right eye and diffuse RNFL thinning of the left eye.
microglia and macrophages—the key players in the acute inflammatory lesions.5 Extensive research has found that the neurodegenerative phase of the disease is not exclusively dependent on inflammation. There is increasing evidence that mitochondria, the site of aerobic respiration and adenosine-50 -triphosphate synthesis within the cell, are crucial organelles for maintenance of axonal integrity in the CNS. For example, mitochondrial dysfunction can lead to catastrophic neurologic disorders such as mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes and myoclonic epilepsy with raggedred fibres.6 In addition, MS has not only been associated with LHON, but another ophthalmic mitochondrial disease: chronic progressive external ophthalmoplegia.7 Tissue injury caused by mitochondrial dysfunction has been shown to be caused by at least 3 different mechanisms8: reactive oxygen species production, energy failure, and apoptosis induction. In the acute MS lesion, axonal degeneration is believed to result from glutamate excitotoxicity9 and increased nitric oxide levels released by macrophages, leading to loss of mitochondrial function, inhibition of aerobic respiration, and production of toxic free radical in demyelinated axons.10 In the chronic MS plaque, studies have shown that loss of myelin and the resultant negative effects on “salutatory conduction” leads to increased energy demand from mitochondria. In myelinated axons within the CNS, more than 90% of
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mitochondria are located within the juxtaparanodal and internodal regions of the axon.11 Altered distribution of voltage-gated channels and increased energy requirements causes increased axoplasmic calcium concentrations, which stimulates proapoptotic pathways within the existing mitochondria.8,12 The fact that small-diameter axons are preferentially lost in MS further implicates mitochondria as a critical player in axonal loss.13 The lack of volume relative to surface area in small-diameter axons correlates to a reduced “energy to ions” ratio, thus making these axons more vulnerable to degeneration.6 Further evidence linking mitochondrial dysfunction to MS has been investigated through electron microscopic evaluation of postmortem tissue, showing decreased numbers of mitochondria and microtubules within demyelinated lesions.14 In addition, studies in experimental autoimmune encephalomyelitis, an animal model of MS, have demonstrated that maintenance of mitochondrial integrity can affect disease progression and axonal survival.15 Abnormal mitochondrial morphology was noted to be the earliest ultrastructural sign of damage, preceding structural changes. Mitochondria are ubiquitous cellular organelles that are vital for the survival of eukaryotic cells. There is an increasing body of evidence that mitochondrial function and response to stress play a significant role in the neurodegenerative process that leads to permanent disability in patients with MS and LHON.16,17 Further insights into
CAN J OPHTHALMOL — VOL. 50, NO. 1, FEBRUARY 2015
Correspondence the molecular mechanisms of MS and LHON will be critical in the development of novel neuroprotective and neuroregenerative therapeutic approaches with the ultimate hope of one day curing these debilitating diseases.18
Disclosure: The authors have no proprietary or commercial interest in any materials discussed in this article. Supported by: This work was supported by an unrestricted departmental grant from Research to Prevent Blindness, Inc.
Varsha Manjunath, M. Tariq Bhatti Duke University Eye Center, Duke University Medical Center, Durham, N.C. Correspondence to: M. Tariq Bhatti, MD: [email protected] REFERENCES 1. Kovacs GG, Hoftberger R, Majtenyi K, et al. Neuropathology of white matter disease in Leber’s hereditary optic neuropathy. Brain. 2005;128:35-41. 2. Lublin F. History of modern multiple sclerosis therapy. J Neurol. 2005;252(Suppl 3):iii3-9. 3. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med. 2000;343:938-52. 4. Trapp BD, Nave KA. Multiple sclerosis: an immune or neurodegenerative disorder? Annu Rev Neurosci. 2008;31:247-69. 5. Huitinga I, van Rooijen N, de Groot CJ, Uitdehaag BM, Dijkstra CD. Suppression of experimental allergic encephalomyelitis in Lewis rats after elimination of macrophages. J Exp Med. 1990;172: 1025-33. 6. Campbell GR, Ohno N, Turnbull DM, Mahad DJ. Mitochondrial changes within axons in multiple sclerosis: an update. Curr Opin Neurol. 2012;25:221-30.
Transient corneal edema circumscribed to the LASIK flap after uneventful cataract surgery Previous studies have shown how LASIK surgery induces long-term changes in the corneal flap,1 the LASIK interface,2 and the residual stromal bed.3 Dawson et al.4 have reported different hydraulic behaviours between stromal bed and LASIK flap in human eye bank corneas, in 2 experimental models of interface fluid syndrome. We present a case of transient corneal edema after cataract surgery, confined to the LASIK flap. This would confirm, in vivo, the different hydraulic behaviour of the LASIK flap compared with the stromal bed and the rest of the cornea. A 58-year-old male was referred to our clinic for cataract surgery in his left eye. Seven years before he had had an uneventful femtosecond LASIK surgery to correct a refractive error of –4.00, –0.75 901 in his left eye with plano result. He had a nuclear cataract, 2530 endothelial cells/mm2, and the central corneal thickness
7. Slee M, Krupa M, Raghupathi R, et al. A novel mitochondrial DNA deletion producing progressive external ophthalmoplegia associated with multiple sclerosis. J Clin Neurosci. 2011;18:1318-24. 8. Lassmann H, van Horssen J. The molecular basis of neurodegeneration in multiple sclerosis. FEBS Lett. 2011;585:3715-23. 9. Kostic M, Zivkovic N, Stojanovic I. Multiple sclerosis and glutamate excitotoxicity. Rev Neurosci. 2013;24:71-88. 10. Lu F, Selak M, O’Connor J, et al. Oxidative damage to mitochondrial DNA and activity of mitochondrial enzymes in chronic active lesions of multiple sclerosis. J Neurol Sci. 2000;177:95-103. 11. Campbell GR, Mahad DJ. Mitochondrial changes associated with demyelination: consequences for axonal integrity. Mitochondrion. 2012;12:173-9. 12. Waxman SG. Axonal conduction and injury in multiple sclerosis: the role of sodium channels. Nat Rev Neurosci. 2006;7:932-41. 13. DeLuca GC, Ebers GC, Esiri MM. Axonal loss in multiple sclerosis: a pathological survey of the corticospinal and sensory tracts. Brain. 2004;127(Pt 5):1009-18. 14. Dutta R, McDonough J, Yin X, et al. Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients. Ann Neurol. 2006;59:478-89. 15. Nikic I, Merkler D, Sorbara C, et al. A reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis. Nat Med. 2011;17:495-9. 16. Su KG, Banker G, Bourdette D, Forte M. Axonal degeneration in multiple sclerosis: the mitochondrial hypothesis. Curr Neurol Neurosci. 2009;Rep 9:411-7. 17. Durastanti V, Monaco A, Caronti B, et al. Mitochondrial genome profile in demyelinating disease. J Neurol Neurophysiol. 2013;5:179. 18. Koilkonda RD, Guy J. Leber’s hereditary optic neuropathy-gene therapy: from benchtop to bedside. J Ophthalmol. 2011;2011: 179412.
Can J Ophthalmol 2015;50:e14–e17 0008-4182/15/$-see front matter & 2015 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcjo.2014.10.018
was 520 μm measured by ultrasonic pachymeter. He had neither signs nor family history of glaucoma. An uneventful phacoemulsification technique was performed, and a monofocal intraocular lens was implanted. The patient was instructed to apply topical antibiotic and steroid drops every 6 hours. On postoperative day 1, the uncorrected distance visual acuity was 20/80. The slit-lamp examination showed corneal edema circumscribed to the LASIK flap (Fig. 1); the underlying residual stromal bed and cornea surrounding the flap limits were clear. The intraocular pressure (IOP) was 25 mm Hg and the lens was correctly positioned in the capsular bag. No fluid was detected in the interface between the flap and the stromal bed with the anterior segment optical coherence tomography (Fig. 2). Topical timolol maleate twice a day and hyperosmotic eye drops 3 times daily were prescribed in addition. One week later, the UCVA improved to 20/25, the flap edema was completely resolved, and IOP was 16 mm Hg. Corneal hydration is determined by factors such as endothelial pump, epithelial barrier, water evaporation,
CAN J OPHTHALMOL — VOL. 50, NO. 1, FEBRUARY 2015
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