- Email: [email protected]
Posterior vitreous detachment and retinal tear after repetitive transcranial magnetic stimulation
Brain Stimulation (2011) 4, 218–21
www.brainstimjrnl.com
Posterior vitreous detachment and retinal tear after repetitive transcranial magnetic stimulation Simon Kung,a Yachna Ahuja,b Raymond Iezzi,b Shirlene M. Sampsona a b
Mayo Clinic Department of Psychiatry and Psychology, Rochester, Minneapolis Mayo Clinic Department of Ophthalmology, Rochester, Minneapolis
This case report describes a 60-year-old woman who experienced a posterior vitreous detachment (PVD) and retinal tear after her 11th session of 1 Hz repetitive transcranial magnetic stimulation (rTMS) for the treatment of major depression. Although we cannot conclude that rTMS caused her PVD and retinal tear, the temporal association is strong, and we hypothesize a possible pathophysiology of the event. As part of the routine clinical monitoring of rTMS side effects, we encourage attention toward ophthalmologic symptoms, especially in older patients. Ó 2011 Elsevier Inc. All rights reserved. Keywords
transcranial magnetic stimulation; depression; posterior vitreous detachment; retinal tear
Since the early 1990s, repetitive transcranial magnetic stimulation (rTMS) has been studied for the treatment of depression, and the 2010 update of the Avery-GeorgeHoltzheimer rTMS for depression database tabulates 142 published research studies comprising over 1000 patients.1 Since the US Food and Drug Administration (FDA) approved the use of a specific rTMS device (NeuroStar, Neuronetics, Malvern, PA) for the treatment of depression in October 2008, additional patients have been clinically treated. Several trials have demonstrated the favorable safety and tolerability profile of rTMS.2,3 Common side effects include headache, scalp discomfort, and eye pain.3 The most concerning adverse effect is seizure, which is rare. The Rossi et al.4 2009 update on safety guidelines has no mention of ophthalmologic side effects. To date,
Correspondence: Dr. Simon Kung, Mayo Clinic, Department of Psychiatry and Psychology, Rochester, MN 55905. E-mail address: [email protected] Submitted April 13, 2011; revised July 11, 2011. Accepted for publication August 12, 2011. 1935-861X/$ - see front matter Ó 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.brs.2011.08.007
there have been no reported association of rTMS with posterior vitreous detachment (PVD) or retinal tear.
Case report The patient was a 60-year-old married white woman with major depressive disorder and work-related chronic mechanical low back and hip pain. She had no other active medical issues, with past history of asthma, deep venous thrombosis, mild pulmonary hypertension, lung nodule biopsy, hysterectomy, and obstructive sleep apnea. Her medications throughout rTMS consisted of duloxetine 120 mg daily, trazodone 150 mg nightly, oxycodone controlled release 40 mg twice a day, and lidocaine 5% (700 mg/patch) one to two patches every day applied to areas of pain. At her initial rTMS session, she had difficulty remaining in the chair because of her back pain, so treatment was canceled and for subsequent treatments, she took oxycodone 10 mg 1 hour before rTMS sessions, which allowed her to tolerate sitting through each session.
PVD and retinal tear after rTMS Pretreatment baseline depression rating scales showed Patient Health Questionnaire (PHQ-9) of 27 and Beck Depression Inventory (BDI-II) of 41. She began rTMS (with the NeuroStar device) for depression with right-sided slow frequency (1 Hz) stimulation.5,6 Each treatment consisted of three 1000 second trains with a 1 minute intertrain interval, for a total of 3000 pulses delivered over 50 minutes at 110% of motor threshold (MT). In NeuroStar terminology using 1.0 as a standardized MT, her ‘‘MT units’’ was 1.13. The MT location was determined by a visual contralateral abductor pollicis brevis (thumb) contraction. The treatment location was approximated to the right dorsolateral prefrontal cortex by moving 5 cm anteriorly from the MT location. rTMS has also been reported to improve chronic pain.7 Pre- and postprocedure pain questions were asked, and she reported benefit in her chronic pain with each treatment, noting right hip pain improvement lasting until the next day’s treatment. Typically her pretreatment pain was rated 5-6 of 10, 10 5 worst, and her posttreatment pain was rated 0-4 of 10. Despite using oxycodone an hour before treatments, she thought her posttreatment pain improvement was maintained until the next day. After her 10th treatment, her PHQ-9 was 19 and BDI-II was 32, reflecting mood improvement of 30% and 22%, respectively, compared with baseline. During her first 10 treatments, she experienced tolerable right eye twitching and discomfort, which is not unusual for patients receiving rTMS. We redetermined her MT before her 11th treatment per our clinical protocol of reassessing MT every 10 treatments. The psychiatrist performing this MT was different from the psychiatrist who performed the first MT. During the first redetermination attempt, there was difficulty isolating the thumb contraction, and the resulting MT intensity (1.40 MT units) reached the maximum level allowed by the device. We considered it to be too high, and a second attempt resulted in a more acceptable MT (1.15 MT units), which was similar to her previous MT. The new MT location was approximately 3 cm more anterior than the previous location, and thus although the new treatment location was still 5 cm anterior to the MT location, it was basically 8 cm anterior to the first treatment’s MT location. The treatment commenced with this new location. After the treatment, her overall pain was rated 6 of 10, focused on her chronic pain. She did not report any ophthalmologic complaints. A few hours later in the afternoon, she presented to her primary care provider for a chief complaint of headache, and there was no documentation of ophthalmologic symptoms. The next day when she presented for her 12th treatment, she reported that after completing the previous day’s treatment, by the time she left the chair and walked to the door she had noticed three new floaters in her right eye vision, which had not resolved overnight. She reported more than usual right eye twitching and discomfort during that 11th treatment. As the discomfort was tolerable, she did not alert the rTMS nurse who had remained in the room with her
219 throughout each treatment. Her 12th treatment was canceled and she was referred to Ophthalmology. A thorough ophthalmologic history was obtained that was significant only for moderate myopia with a spherical equivalent of 23.00 to 24.00 diopters in her eyes. She denied any prior eye surgeries or trauma. She also denied any family history of retinal tears or detachments. Her examination revealed a visual acuity of 20/40, improving with pinhole to 20/20 in her right eye and 20/20 vision in her left eye. Intraocular pressure was within normal limits. Dilated examination of the right eye revealed a PVD with 11 pigment in the vitreous. There was a small peripheral horseshoe tear at 12:00, anterior to the equator of the globe. There was a trace of subretinal fluid temporal to the tear and the remaining retina was flat. There were no peripheral retinal degenerations such as lattice degeneration that could predispose the patient to a retinal tear. She underwent laser retinopexy treatment of the tear with 289 burns of argon laser at 250 mW with a 200-mm spot size and 0.1 second duration. Because the patient thought that rTMS was beneficial for her mood and chronic pain, she was motivated to continue. We were also initially unclear as to how rTMS could have caused the PVD and retinal tear, as there had been no previous reports. The treating rTMS psychiatrist discussed the implications of the PVD and retinal tear with her, and both agreed to continue with rTMS. Before the next treatment (3 days after the retinal tear repair, and 4 days after the 11th rTMS session), a new MT determination resulted in an intensity (1.09 MT units) and location (only 0.5 cm anterior to the location from the first treatment) similar to the first 10 treatments. She underwent another three treatments without incident at 110% of MT. During her 15th treatment, she experienced a shower of several black dots in her right eye for about 5 seconds. She coincidentally then had her 1-week postlaser surgery follow-up, and reported that her floaters had lightened. The visual acuity of her right eye had improved to 20/30 with a pinhole acuity of 20/25. The horseshoe retinal tear in her right eye was well-surrounded by laser scars and there was no surrounding subretinal fluid. We stopped rTMS at the recommendation of her ophthalmologist, which was disappointing for her because she thought rTMS had been helpful. We reported this clinical sequence of events to the device manufacturer, who had not received any other reports of PVDs or retinal tear with their device.
Discussion A PVD is an age-related degenerative process in which the vitreous cortex in the eye separates from the retina. PVDs can occur spontaneously or secondary to trauma or rapid rotation of the eye. The presenting symptoms of a PVD include a sudden-onset of floaters in the vision, with or without flashes of light. The prevalence of PVDs increases
220 with age with a prevalence of 24% by the age of 60 and 87% by the age of 90.8 Other risk factors for PVDs include trauma, inflammation, and intraocular surgery. PVDs can develop earlier in severely high myopes (greater than 210 diopters) than in moderately high myopia (between 26 to 210 diopters).9 In this case, our patient had moderate myopia with a spherical equivalent of 23.00 to 24.00 diopters. PVDs are the principal predisposing event for the development of retinal breaks and rhegmatogenous retinal detachments. At the initial examination, more than 10% of patients with symptomatic PVD may have retinal tears or retinal detachments.10 Risk factors for developing retinal tears and detachments include age, trauma, myopia, family history, and preexisting retinal degenerative conditions. Our initial thought was that the patient’s PVD and retinal tear were unrelated to rTMS, as there have been no previous reports of such an association. It would not be unusual for persons with myopia to have background floaters. It cannot be ruled out that her PVD and retinal tear were preexisting conditions. However, the symptoms of new floaters occurring almost immediately after a treatment session suggested an association. Perhaps she was already at higher risk of PVDs and retinal tears, and rTMS was a catalyst for further progression of these conditions. Potential mechanisms of action for how rTMS might cause a PVD or retinal tear were explored. The patient’s risk factors included age and the possible mechanical effects of rTMS acting as trauma. Cocontraction of the extraocular muscles and orbicularis oculi could cause rapid repetitive eye movements and secondary retinal trauma because of the mechanical coupling of the vitreous body to the retina. Indeed, during clinical treatments of patients, we routinely observe the eyelid twitching, and underlying eye movements could be expected. We hypothesize that rTMS may have caused significant contraction of her extraocular muscles to generate a force resulting in transient distortion of her eye, thereby leading to a PVD and retinal tear. If the extraocular muscles around the eye were persistently ‘‘twitching’’ throughout the treatment, then it is possible that the vigorous vibration could be conducted to the insertion points of the muscles on the globe. In our patient, her retinal tear was in the proximity of the insertion points of two of the superior muscles. In our patient, we do not believe that the electric field distribution of the TMS coil directly affected her eye. The penetration of current TMS coils is estimated to be 1.53 cm beneath the scalp.4 A standard figure-of-eight coil was modeled to a depth of 1.5 cm and two different H-coil designs were modeled to 2-6 cm depending on placement location.11 An iron-core coil, or a ferromagnetic core coil of the device we used, can penetrate about 2 cm with a wider field.12 The coil rotation angle can also affect the electrical field. When we reconstructed our coil placement with the patient 2 weeks after the PVD and retinal tear, the distance between the coil and her eye was greater than 2 cm. However, breaks in the bony insulation of the head,
Kung et al such as the orbit, can allow electrical current to be more concentrated in those areas, allowing greater field penetration. Also, it has been reported that the eye has a lower threshold for magnetic stimulation than the occipital cortex as it relates to generating phosphenes (the perception of flashes of light), with a theory of mechanical torque of the retinal rods related to its magnetic susceptibility.13 Our patient did not report any perception of flashes of light during the 11th treatment. If there might be a direct effect of TMS electric field distribution on the eye, then the use of H-coils that can penetrate deeper might be of more concern. The indirect effects of TMS beyond the estimated 1.53.0 cm stimulation depth, such as focal sensations or muscle movements, can be experienced and observed. In a randomized rTMS trial for depression, adverse events experienced by the active TMS group (n 5 165) at a rate R5% and at least twice that of the sham group (n 5 158) included application site pain (35.8%), muscle twitching (20.6%), application site discomfort (10.9%), skin pain (8.5%), toothache (7.3%), facial pain (6.7%), and eye pain (6.1%).3 Even though eye pain was one of the less common adverse events, it was still 6.1%, indicating that rTMS can affect the eye despite the coil not being in close proximity to the eye. Eyelid twitching is also common during rTMS treatments. Our patient experienced tolerable facial twitching and eye pain throughout the first 10 treatments, and greater pain during the 11th treatment. There are factors that might explain why the PVD and retinal tear occurred after the 11th treatment and not earlier. Different psychiatrists performed the MT at the first and the 11th treatment, and thus there was operator variability. Patient variability factors related to medications (although our patient was on a stable regimen of medications throughout treatments), emotional stress, sleep deprivation, and tiredness can also alter motor threshold.14 Visual determination of the optimal MT location could result in a range of acceptable locations. Although she was subjected to higher stimulation intensities during MT determination, her treatment intensity was not significantly higher than previous treatments after the second MT reassessment. However, the MT located resulted in a treatment position closer to the eye than during the first 10 treatments. This closer proximity might have also resulted in more forceful extraocular muscle contractions. Research suggests that the optimal treatment location with rTMS is more anterior (thus closer to the eye) and lateral than the location we currently use in clinical practice, and there are suggestions of using a 7-cm instead of a 5-cm position.15,16 Other methods of determining the treatment location, such as the F3 system, might also position the coil closer to the eye.17 Based on our case, ophthalmologic symptom monitoring would be important if a more anterior position were used. Being that age is a risk factor for PVDs, we considered whether not enough patients greater than 60 years have been treated with rTMS to yield other cases of PVDs associated
PVD and retinal tear after rTMS with rTMS. Typically, the majority of patients in rTMS studies were younger than age 60, with one trial reporting an average age of 47.9 6 11.0 years and a second trial reporting 47.7 6 10.6 years.2,18 TMS has been used in research studies of Alzheimer’s and Parkinson’s, in which patients are older. However, many of these studies used limited stimulation targeted to the motor cortex. There are a few newer studies involving rTMS over the dorsolateral prefrontal cortex, but with a small number of subjects.19,20 It is not possible to conclude that rTMS is causative in the development of a PVD and retinal tear in our patient. However, we note the association, because of the temporal sequence of the treatment and her ophthalmologic symptoms. Thousands of rTMS sessions have been safely conducted worldwide in research and clinical settings, and ours is the first, and perhaps will be the last, reported case of such an association. Clinicians should monitor the effects of rTMS on the extraocular muscles, and exercise caution when a patient, especially an older patient, reports any new ophthalmologic symptoms such as floaters, flashes of light, decreased vision, or eye discomfort.
References 1. Polley KH, Navarro R, Avery DH, George MS, Holtzheimer PE. 2010 updated Avery-George-Holtzheimer database of rTMS depression studies. Brain Stimul 2011;4(2):115-116. 2. George MS, Lisanby SH, Avery D, et al. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Arch Gen Psychiatry 2010; 67(5):507-516. 3. Janicak PG, O’Reardon JP, Sampson SM, et al. Transcranial magnetic stimulation in the treatment of major depressive disorder: a comprehensive summary of safety experience from acute exposure, extended exposure, and during reintroduction treatment. J Clin Psychiatry 2008; 69(2):222-232. 4. Rossi S, Hallett M, Rossini PM, Pascual-Leone A, Group SoTC. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol 2009;120(12):2008-2039. 5. Kauffmann CD, Cheema MA, Miller BE. Slow right prefrontal transcranial magnetic stimulation as a treatment for medication-resistant
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depression: a double-blind, placebo-controlled study. Depress Anxiety 2004;19(1):59-62. Klein E, Kreinin I, Chistyakov A, et al. Therapeutic efficacy of right prefrontal slow repetitive transcranial magnetic stimulation in major depression. Arch Gen Psychiatry 1999;56:315-320. Sampson SM, Kung S, McAlpine DE, Sandroni P. The use of slowfrequency prefrontal repetitive transcranial magnetic stimulation in refractory neuropathic pain. J ECT 2011;27(1):33-37. Hikichi T, Hirokawa H, Kado M, et al. Comparison of the prevalence of posterior vitreous detachment in whites and Japanese. Ophthalmic Surg 1995;26(1):39-43. Akiba J. Prevalence of posterior vitreous detachment in high myopia. Ophthalmology 1993;100(9):1384-1388. Hikichi T, Trempe CL. Relationship between floaters, light flashes, or both, and complications of posterior vitreous detachment. Am J Ophthalmol 1994;117(5):593-598. Roth Y, Amir A, Levkovitz Y, Zangen A. Three-dimensional distribution of the electric field induced in the brain by transcranial magnetic stimulation using figure-8 and deep H-coils. J Clin Neurophysiol 2007;24(1):31-38. Epstein CM, Davey KR. Iron-core coils for transcranial magnetic stimulation. J Clin Neurophysiol 2002;19(4):376-381. Marg E. Magnetostimulation of vision: direct noninvasive stimulation of the retina and the visual brain. Optom Vis Sci 1991;68(6):427-440. Nakken KO, Solaas MH, Kjeldsen MJ, Friis ML, Pellock JM, Corey LA. Which seizure-precipitating factors do patients with epilepsy most frequently report? Epilepsy Behav 2005;6(1):85-89. George MS, Post RM. Daily left prefrontal repetitive transcranial magnetic stimulation for acute treatment of medication-resistant depression. Am J Psychiatry 2011;168(4):356-364. Herbsman T, Avery D, Ramsey D, et al. More lateral and anterior prefrontal coil location is associated with better repetitive transcranial magnetic stimulation antidepressant response. Biol Psychiatry 2009; 66(5):509-515. Beam W, Borckardt JJ, Reeves ST, George MS. An efficient and accurate new method for locating the F3 position for prefrontal TMS applications. Brain Stimul 2009;2(1):50-54. O’Reardon JP, Solvason HB, Janicak PG, et al. Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biol Psychiatry 2007;62(11):1208-1216. Cotelli M, Calabria M, Manenti R, et al. Improved language performance in Alzheimer disease following brain stimulation. J Neurol Neurosurg Psychiatry 2011;82(7):794-797. Filipovic SR, Rothwell JC, Bhatia K. Slow (1 Hz) repetitive transcranial magnetic stimulation (rTMS) induces a sustained change in cortical excitability in patients with Parkinson’s disease. Clin Neurophysiol 2010;121(7):1129-1137.
www.brainstimjrnl.com
Posterior vitreous detachment and retinal tear after repetitive transcranial magnetic stimulation Simon Kung,a Yachna Ahuja,b Raymond Iezzi,b Shirlene M. Sampsona a b
Mayo Clinic Department of Psychiatry and Psychology, Rochester, Minneapolis Mayo Clinic Department of Ophthalmology, Rochester, Minneapolis
This case report describes a 60-year-old woman who experienced a posterior vitreous detachment (PVD) and retinal tear after her 11th session of 1 Hz repetitive transcranial magnetic stimulation (rTMS) for the treatment of major depression. Although we cannot conclude that rTMS caused her PVD and retinal tear, the temporal association is strong, and we hypothesize a possible pathophysiology of the event. As part of the routine clinical monitoring of rTMS side effects, we encourage attention toward ophthalmologic symptoms, especially in older patients. Ó 2011 Elsevier Inc. All rights reserved. Keywords
transcranial magnetic stimulation; depression; posterior vitreous detachment; retinal tear
Since the early 1990s, repetitive transcranial magnetic stimulation (rTMS) has been studied for the treatment of depression, and the 2010 update of the Avery-GeorgeHoltzheimer rTMS for depression database tabulates 142 published research studies comprising over 1000 patients.1 Since the US Food and Drug Administration (FDA) approved the use of a specific rTMS device (NeuroStar, Neuronetics, Malvern, PA) for the treatment of depression in October 2008, additional patients have been clinically treated. Several trials have demonstrated the favorable safety and tolerability profile of rTMS.2,3 Common side effects include headache, scalp discomfort, and eye pain.3 The most concerning adverse effect is seizure, which is rare. The Rossi et al.4 2009 update on safety guidelines has no mention of ophthalmologic side effects. To date,
Correspondence: Dr. Simon Kung, Mayo Clinic, Department of Psychiatry and Psychology, Rochester, MN 55905. E-mail address: [email protected] Submitted April 13, 2011; revised July 11, 2011. Accepted for publication August 12, 2011. 1935-861X/$ - see front matter Ó 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.brs.2011.08.007
there have been no reported association of rTMS with posterior vitreous detachment (PVD) or retinal tear.
Case report The patient was a 60-year-old married white woman with major depressive disorder and work-related chronic mechanical low back and hip pain. She had no other active medical issues, with past history of asthma, deep venous thrombosis, mild pulmonary hypertension, lung nodule biopsy, hysterectomy, and obstructive sleep apnea. Her medications throughout rTMS consisted of duloxetine 120 mg daily, trazodone 150 mg nightly, oxycodone controlled release 40 mg twice a day, and lidocaine 5% (700 mg/patch) one to two patches every day applied to areas of pain. At her initial rTMS session, she had difficulty remaining in the chair because of her back pain, so treatment was canceled and for subsequent treatments, she took oxycodone 10 mg 1 hour before rTMS sessions, which allowed her to tolerate sitting through each session.
PVD and retinal tear after rTMS Pretreatment baseline depression rating scales showed Patient Health Questionnaire (PHQ-9) of 27 and Beck Depression Inventory (BDI-II) of 41. She began rTMS (with the NeuroStar device) for depression with right-sided slow frequency (1 Hz) stimulation.5,6 Each treatment consisted of three 1000 second trains with a 1 minute intertrain interval, for a total of 3000 pulses delivered over 50 minutes at 110% of motor threshold (MT). In NeuroStar terminology using 1.0 as a standardized MT, her ‘‘MT units’’ was 1.13. The MT location was determined by a visual contralateral abductor pollicis brevis (thumb) contraction. The treatment location was approximated to the right dorsolateral prefrontal cortex by moving 5 cm anteriorly from the MT location. rTMS has also been reported to improve chronic pain.7 Pre- and postprocedure pain questions were asked, and she reported benefit in her chronic pain with each treatment, noting right hip pain improvement lasting until the next day’s treatment. Typically her pretreatment pain was rated 5-6 of 10, 10 5 worst, and her posttreatment pain was rated 0-4 of 10. Despite using oxycodone an hour before treatments, she thought her posttreatment pain improvement was maintained until the next day. After her 10th treatment, her PHQ-9 was 19 and BDI-II was 32, reflecting mood improvement of 30% and 22%, respectively, compared with baseline. During her first 10 treatments, she experienced tolerable right eye twitching and discomfort, which is not unusual for patients receiving rTMS. We redetermined her MT before her 11th treatment per our clinical protocol of reassessing MT every 10 treatments. The psychiatrist performing this MT was different from the psychiatrist who performed the first MT. During the first redetermination attempt, there was difficulty isolating the thumb contraction, and the resulting MT intensity (1.40 MT units) reached the maximum level allowed by the device. We considered it to be too high, and a second attempt resulted in a more acceptable MT (1.15 MT units), which was similar to her previous MT. The new MT location was approximately 3 cm more anterior than the previous location, and thus although the new treatment location was still 5 cm anterior to the MT location, it was basically 8 cm anterior to the first treatment’s MT location. The treatment commenced with this new location. After the treatment, her overall pain was rated 6 of 10, focused on her chronic pain. She did not report any ophthalmologic complaints. A few hours later in the afternoon, she presented to her primary care provider for a chief complaint of headache, and there was no documentation of ophthalmologic symptoms. The next day when she presented for her 12th treatment, she reported that after completing the previous day’s treatment, by the time she left the chair and walked to the door she had noticed three new floaters in her right eye vision, which had not resolved overnight. She reported more than usual right eye twitching and discomfort during that 11th treatment. As the discomfort was tolerable, she did not alert the rTMS nurse who had remained in the room with her
219 throughout each treatment. Her 12th treatment was canceled and she was referred to Ophthalmology. A thorough ophthalmologic history was obtained that was significant only for moderate myopia with a spherical equivalent of 23.00 to 24.00 diopters in her eyes. She denied any prior eye surgeries or trauma. She also denied any family history of retinal tears or detachments. Her examination revealed a visual acuity of 20/40, improving with pinhole to 20/20 in her right eye and 20/20 vision in her left eye. Intraocular pressure was within normal limits. Dilated examination of the right eye revealed a PVD with 11 pigment in the vitreous. There was a small peripheral horseshoe tear at 12:00, anterior to the equator of the globe. There was a trace of subretinal fluid temporal to the tear and the remaining retina was flat. There were no peripheral retinal degenerations such as lattice degeneration that could predispose the patient to a retinal tear. She underwent laser retinopexy treatment of the tear with 289 burns of argon laser at 250 mW with a 200-mm spot size and 0.1 second duration. Because the patient thought that rTMS was beneficial for her mood and chronic pain, she was motivated to continue. We were also initially unclear as to how rTMS could have caused the PVD and retinal tear, as there had been no previous reports. The treating rTMS psychiatrist discussed the implications of the PVD and retinal tear with her, and both agreed to continue with rTMS. Before the next treatment (3 days after the retinal tear repair, and 4 days after the 11th rTMS session), a new MT determination resulted in an intensity (1.09 MT units) and location (only 0.5 cm anterior to the location from the first treatment) similar to the first 10 treatments. She underwent another three treatments without incident at 110% of MT. During her 15th treatment, she experienced a shower of several black dots in her right eye for about 5 seconds. She coincidentally then had her 1-week postlaser surgery follow-up, and reported that her floaters had lightened. The visual acuity of her right eye had improved to 20/30 with a pinhole acuity of 20/25. The horseshoe retinal tear in her right eye was well-surrounded by laser scars and there was no surrounding subretinal fluid. We stopped rTMS at the recommendation of her ophthalmologist, which was disappointing for her because she thought rTMS had been helpful. We reported this clinical sequence of events to the device manufacturer, who had not received any other reports of PVDs or retinal tear with their device.
Discussion A PVD is an age-related degenerative process in which the vitreous cortex in the eye separates from the retina. PVDs can occur spontaneously or secondary to trauma or rapid rotation of the eye. The presenting symptoms of a PVD include a sudden-onset of floaters in the vision, with or without flashes of light. The prevalence of PVDs increases
220 with age with a prevalence of 24% by the age of 60 and 87% by the age of 90.8 Other risk factors for PVDs include trauma, inflammation, and intraocular surgery. PVDs can develop earlier in severely high myopes (greater than 210 diopters) than in moderately high myopia (between 26 to 210 diopters).9 In this case, our patient had moderate myopia with a spherical equivalent of 23.00 to 24.00 diopters. PVDs are the principal predisposing event for the development of retinal breaks and rhegmatogenous retinal detachments. At the initial examination, more than 10% of patients with symptomatic PVD may have retinal tears or retinal detachments.10 Risk factors for developing retinal tears and detachments include age, trauma, myopia, family history, and preexisting retinal degenerative conditions. Our initial thought was that the patient’s PVD and retinal tear were unrelated to rTMS, as there have been no previous reports of such an association. It would not be unusual for persons with myopia to have background floaters. It cannot be ruled out that her PVD and retinal tear were preexisting conditions. However, the symptoms of new floaters occurring almost immediately after a treatment session suggested an association. Perhaps she was already at higher risk of PVDs and retinal tears, and rTMS was a catalyst for further progression of these conditions. Potential mechanisms of action for how rTMS might cause a PVD or retinal tear were explored. The patient’s risk factors included age and the possible mechanical effects of rTMS acting as trauma. Cocontraction of the extraocular muscles and orbicularis oculi could cause rapid repetitive eye movements and secondary retinal trauma because of the mechanical coupling of the vitreous body to the retina. Indeed, during clinical treatments of patients, we routinely observe the eyelid twitching, and underlying eye movements could be expected. We hypothesize that rTMS may have caused significant contraction of her extraocular muscles to generate a force resulting in transient distortion of her eye, thereby leading to a PVD and retinal tear. If the extraocular muscles around the eye were persistently ‘‘twitching’’ throughout the treatment, then it is possible that the vigorous vibration could be conducted to the insertion points of the muscles on the globe. In our patient, her retinal tear was in the proximity of the insertion points of two of the superior muscles. In our patient, we do not believe that the electric field distribution of the TMS coil directly affected her eye. The penetration of current TMS coils is estimated to be 1.53 cm beneath the scalp.4 A standard figure-of-eight coil was modeled to a depth of 1.5 cm and two different H-coil designs were modeled to 2-6 cm depending on placement location.11 An iron-core coil, or a ferromagnetic core coil of the device we used, can penetrate about 2 cm with a wider field.12 The coil rotation angle can also affect the electrical field. When we reconstructed our coil placement with the patient 2 weeks after the PVD and retinal tear, the distance between the coil and her eye was greater than 2 cm. However, breaks in the bony insulation of the head,
Kung et al such as the orbit, can allow electrical current to be more concentrated in those areas, allowing greater field penetration. Also, it has been reported that the eye has a lower threshold for magnetic stimulation than the occipital cortex as it relates to generating phosphenes (the perception of flashes of light), with a theory of mechanical torque of the retinal rods related to its magnetic susceptibility.13 Our patient did not report any perception of flashes of light during the 11th treatment. If there might be a direct effect of TMS electric field distribution on the eye, then the use of H-coils that can penetrate deeper might be of more concern. The indirect effects of TMS beyond the estimated 1.53.0 cm stimulation depth, such as focal sensations or muscle movements, can be experienced and observed. In a randomized rTMS trial for depression, adverse events experienced by the active TMS group (n 5 165) at a rate R5% and at least twice that of the sham group (n 5 158) included application site pain (35.8%), muscle twitching (20.6%), application site discomfort (10.9%), skin pain (8.5%), toothache (7.3%), facial pain (6.7%), and eye pain (6.1%).3 Even though eye pain was one of the less common adverse events, it was still 6.1%, indicating that rTMS can affect the eye despite the coil not being in close proximity to the eye. Eyelid twitching is also common during rTMS treatments. Our patient experienced tolerable facial twitching and eye pain throughout the first 10 treatments, and greater pain during the 11th treatment. There are factors that might explain why the PVD and retinal tear occurred after the 11th treatment and not earlier. Different psychiatrists performed the MT at the first and the 11th treatment, and thus there was operator variability. Patient variability factors related to medications (although our patient was on a stable regimen of medications throughout treatments), emotional stress, sleep deprivation, and tiredness can also alter motor threshold.14 Visual determination of the optimal MT location could result in a range of acceptable locations. Although she was subjected to higher stimulation intensities during MT determination, her treatment intensity was not significantly higher than previous treatments after the second MT reassessment. However, the MT located resulted in a treatment position closer to the eye than during the first 10 treatments. This closer proximity might have also resulted in more forceful extraocular muscle contractions. Research suggests that the optimal treatment location with rTMS is more anterior (thus closer to the eye) and lateral than the location we currently use in clinical practice, and there are suggestions of using a 7-cm instead of a 5-cm position.15,16 Other methods of determining the treatment location, such as the F3 system, might also position the coil closer to the eye.17 Based on our case, ophthalmologic symptom monitoring would be important if a more anterior position were used. Being that age is a risk factor for PVDs, we considered whether not enough patients greater than 60 years have been treated with rTMS to yield other cases of PVDs associated
PVD and retinal tear after rTMS with rTMS. Typically, the majority of patients in rTMS studies were younger than age 60, with one trial reporting an average age of 47.9 6 11.0 years and a second trial reporting 47.7 6 10.6 years.2,18 TMS has been used in research studies of Alzheimer’s and Parkinson’s, in which patients are older. However, many of these studies used limited stimulation targeted to the motor cortex. There are a few newer studies involving rTMS over the dorsolateral prefrontal cortex, but with a small number of subjects.19,20 It is not possible to conclude that rTMS is causative in the development of a PVD and retinal tear in our patient. However, we note the association, because of the temporal sequence of the treatment and her ophthalmologic symptoms. Thousands of rTMS sessions have been safely conducted worldwide in research and clinical settings, and ours is the first, and perhaps will be the last, reported case of such an association. Clinicians should monitor the effects of rTMS on the extraocular muscles, and exercise caution when a patient, especially an older patient, reports any new ophthalmologic symptoms such as floaters, flashes of light, decreased vision, or eye discomfort.
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