|Year : 2020 | Volume
| Issue : 3 | Page : 258-262
Trial for a trial: Is there hope? – Optic neuritis treatment trial protocol in patients with traumatic optic neuropathy
Jainy Joseph Emmatty1, Smita Narayan2, Rajini K Cherayath3
1 Department of Ophthalmology, Amala Institute of Medical Sciences, Thrissur, Kerala, India
2 Department of Ophthalmology, Regional Institute of Ophthalmology, Thiruvananthapuram, Kerala, India
3 Department of Ophthalmology, Government Medical College, Manjeri, Kerala, India
|Date of Submission||14-Feb-2020|
|Date of Decision||02-Mar-2020|
|Date of Acceptance||20-Mar-2020|
|Date of Web Publication||23-Dec-2020|
Dr. Smita Narayan
3B, Condor Marigold, Near DPI, Thycaud P.O, Trivandrum - 695 014, Kerala
Source of Support: None, Conflict of Interest: None
Aims: The aim of this study was to analyze the clinical profile, visual outcome, factors predicting the visual outcome, and response to systemic methylprednisolone as per the Optic Neuritis Treatment Trial (ONTT) protocol in patients with traumatic optic neuropathy (TON). Study Design: This was a prospective observational study. Subjects and Methods: All cases who had decreased visual acuity (VA) following impact head/orbital injury were evaluated with detailed history, and ophthalmic evaluation was done. Those who were diagnosed to have indirect TON were treated with intravenous methylprednisolone 500 mg twice daily for 3 days, followed by oral prednisolone 1 mg/kg for 11 days. Visual outcome was assessed at 1 week, 1 month, 3 months, and 6 months. The results were statistically analyzed. Results: 34.65% had severe loss of vision (<6/60 vision) at presentation. Twenty patients received early treatment (within 3 days) and six patients received treatment after 3 days. Fourteen eyes (53.84%) showed an improvement in VA at 1 month. Among those who had early treatment, 60% improved, but it was not statistically significant. An initial VA of <6/60 and the presence of brain contusions were significantly associated with poor visual outcomes. Conclusions: There is no statistically significant improvement in visual outcome with early initiation of therapy. Severe initial visual loss and presence of brain contusions predict poor visual outcomes. Selected patients will benefit with corticosteroids, and the ONTT protocol with minimal adverse reactions would be a safer choice in them.
Keywords: Methylprednisolone, Optic Neuritis Treatment Trial, traumatic optic neuropathy
|How to cite this article:|
Emmatty JJ, Narayan S, Cherayath RK. Trial for a trial: Is there hope? – Optic neuritis treatment trial protocol in patients with traumatic optic neuropathy. Kerala J Ophthalmol 2020;32:258-62
|How to cite this URL:|
Emmatty JJ, Narayan S, Cherayath RK. Trial for a trial: Is there hope? – Optic neuritis treatment trial protocol in patients with traumatic optic neuropathy. Kerala J Ophthalmol [serial online] 2020 [cited 2021 Jan 16];32:258-62. Available from: http://www.kjophthal.com/text.asp?2020/32/3/258/304546
| Introduction|| |
The optic nerve is prone to indirect and direct trauma, causing functional impairment of vision. Optic nerve injuries can occur with head injury due to road traffic accidents (RTAs) or falls. However, the diagnosis of optic nerve injury may be delayed because of focus on other life-threatening injuries. The signs of optic nerve trauma are clinical, and the examination of acutely injured is often difficult. Indirect damage to the optic nerve is the most common form of traumatic optic neuropathy (TON) and is reported following 0.5%–5% of all closed-head trauma. It is defined as traumatic visual loss that occurs without external or initial ophthalmoscopic evidence of injury to the eye or the optic nerve. Indirect injuries occur due to concussive forces that are transmitted to the optic nerve as a result of orbit or cranial trauma. This impact produces a shock wave which leads to optic nerve avulsion or posterior indirect TON. After the immediate injury, swelling of the optic nerve within the canal causes secondary retinal ganglion cell loss. Direct TON, on the other hand, results from direct trauma to the optic nerve from sharp objects, missiles, and bony fragments.
Although TON can be diagnosed by a careful history taking and examination, its appropriate management has not been well defined. Different approaches, including different dosages of steroids (60 mg to 7 g/day), surgical decompression of optic canal (via intracranial, transethmoidal, endonasal, sublabial, or other techniques), and observation alone, have been suggested, but conclusive evidence to establish a standard approach to this devastating cause of visual loss is lacking. Although visual outcome after indirect TON may be quite variable, approximately 50% of the patients are left with “light perception” or “no light perception” vision, making it a significant cause of permanent visual loss.
The role of steroids in TON is controversial. In most cases, the treatment is based on individual decision. Despite being an important cause of permanent visual loss, there are few studies in this regard from Kerala. We undertook this study to identify the clinical profile, associated injuries, visual outcome, prognostic factors, the role of steroids, and the impact of early initiation of therapy in patients with TON. Knowledge of these factors would help in formulating treatment protocol and fuel further research in the field.
| Subjects and Methods|| |
After getting the institutional ethics committee approval, all patients who were diagnosed to have indirect TON were included in the study. However, those with major head trauma, unconscious patients, penetrating eye injury patients, and patients needing decompression surgery were excluded. Those with posttraumatic visual loss not related to optic nerve dysfunction (open-globe injury, traumatic cataract, retinal detachment, choroidal rupture, and vitreous hemorrhage) and those with preexisting visual loss were also excluded.
After getting a detailed informed consent, data were collected regarding age, sex, the cause of blindness (timing and nature of trauma), level of consciousness after trauma, site of injury, onset and duration of symptoms, the time of presentation, and other systemic illness. A baseline neuro-ophthalmic examination for visual acuity (VA), relative afferent pupillary defect (RAPD), field of vision, and color vision was done. Slit-lamp examination was done to rule out penetrating injury, traumatic cataract, hyphema, and uveitis. Ophthalmoscopy was performed to see for optic nerve avulsion, choroidal rupture, and pallor. Extraocular movements were also assessed. X-rays of the skull and the orbit were taken. High-resolution computed tomography (CT) scan of the head and orbit was taken in all cases to assess orbital wall fractures, hemolysins, and to rule out the presence of optic canal fracture or bony fragments impinging the optic nerve. Magnetic resonance imaging was done in those with worsening of vision to look for optic nerve edema in the optic canal, optic nerve sheath hematoma, and intracranial injuries that were inadequately detailed with CT imaging.
Included patients were treated with intravenous methylprednisolone 500 mg twice daily for 3 days, followed by oral prednisolone (1 mg/kg) for 11 days. Visual outcome was assessed at 1 week, 1 month, 3 months, and at 6 months. At each visit, patients' VA, pupillary reaction, color vision, visual fields, and fundus were assessed. Two- or more-line improvement in VA was considered as a significant improvement.
The collected data were analyzed statistically using SPSS version 16.0 (SPSS Inc., 233 South Wacker Drive, Chicago, IL). Quantitative variables are expressed as means and qualitative parameters as proportions. Correlation between the quantitative parameters was analyzed using independent sample Student's t-test and between qualitative parameters using the Chi-square test. P < 0.05 was considered statistically significant.
| Results|| |
Twenty-six eyes of 26 patients were included in the study. The mean age of the patients was 37 years. Patients in the age group of 31–40 years were the most affected (38.45%), followed by the patients in the 21–30 years' age group (34.15%). Out of 26 patients, 25 (96.15%) were male. Mode of injury was RTA in 25 (99.15%) patients, and one patient developed optic neuropathy following an assault. The left eye was involved in 16 patients (61.54%). The side of the face was the site of injury in 15 patients (67.7%) and the forehead in 11 patients (42.3%). There was a history of transient loss of consciousness in nine patients (34.61%).
In our study, nine patients (34.65%) had severe loss of vision (<6/60) at presentation. Grade 1, Grade 2, and Grade 3 RAPDs were seen in 1 patient (3.84%), 14 patients (53.84%), and 11 patients (42.32%), respectively. Extraocular movements were full in 22 patients (84.61%), while mild restriction was noted in 4 patients (15.39%). Fundus was normal in all patients (100%). Associated injuries noted were lacerated wound over ipsilateral forehead/eyebrow in 17 patients (65.38%), periorbital ecchymosis in 24 patients (92.30%), subconjunctival hemorrhage in 22 patients (84.61%), and periorbital emphysema in 7 patients (26.92%). Other injuries seen were degloving injury of the cheek in one patient and avulsion of the pinna in one patient. Radiological findings included minor brain contusions in six patients and multiple bone fractures including the frontal bone and orbital wall fractures (mainly lateral wall and roof). Majority of the patients presented with more than one bony fracture of orbit, and three patients (11.53%) had no fractures.
Twenty patients received early treatment (within 3 days), and six patients received treatment after 3 days [Figure 1]. Treatment was initiated late in six patients (23.08%) due to their delayed presentation. Of the 26 eyes included in the study, 14 eyes (53.84%) showed an improvement in VA at a 1-month follow-up, and thereafter, none improved. Of these, eight patients had shown an improvement in visual outcome within 1 week of initiation of therapy. Two patients deteriorated at the end of 3 months. Primary optic atrophy was seen in ten patients (38.46%) and temporal pallor in nine patients (34.61%) at the end of 1 month. All the patients showed optic disc pallor at the end of 3 months.
Among those who had early treatment, 12 out of 20 eyes (60%) improved while only two of the six eyes (33%) in the late treatment group had a significant improvement in the VA. On the Chi-square test, however, the result did not attain statistical significance (P = 0.365). The mean age of the patients who had good visual outcome following therapy was 35.2 years compared to 37.4 years in the group that had a poor visual outcome. However, this result was not statistically significant (P = 0.562). Of the nine patients who had an initial VA (IVA) <6/60, seven patients (78.78%) had no significant improvement in the final visual outcome. Thus, an IVA of <6/60 was significantly associated with a poor visual outcome (P = 0.038). Among the six patients with brain contusions, only 16.67% had a significant improvement in VA, while 65% of the patients without contusions improved [Figure 2]. The presence of associated brain contusions (83.33% vs. 35%) was associated with poor visual outcomes. The result was statistically significant (P = 0.049).
| Discussion|| |
Twenty eyes of 26 participants were enrolled in our study. Majority of the participants were in the 20–40 years group. This is similar to studies conducted by Sadeghi et al. (mean age of 24.1 years) and Lee et al. (mean age of 33 years). In our study, 96.15% of the patients were male. The male-to-female ratio 3:1 in the study by Sadeghi et al. Motor vehicle accidents accounted for 83.3% of injuries in our study. Similar findings were showed in Sadeghi et al. study (71.4%) and Lee et al. study (83.3%).
The most common site of indirect optic nerve injury is in the optic canal. Chou et al. had proposed that the damage of optic nerve at microscopic level, including contusion necrosis, nerve fiber tears and nerve infarction secondary to closed-space edema, hemorrhage, thrombosis, vasospasm, impingement by bone spicules, and shearing of dural vessels in the optic canal could result in TON. The ocular manifestations most commonly associated with optic nerve injury were periorbital hematoma and subconjunctival hemorrhage, with no changes in the optic nerve. Periorbital hematoma was present in all cases in the study by Lee et al. In our study, periorbital ecchymosis was seen in 24 patients (92.30%) and subconjunctival hemorrhage in 22 patients (84.61%).
Our study showed that majority of the patients (82.46%) presented with more than one bony fracture of the orbit and 3 patients (11.53%) had no fractures. Lee et al. observed that 79.2% of the patients presented with more than one bony fracture of the skull and/or orbit and 5 patients (20.8%) had no fractures. The presence of these signs may suggest the presence of TON in cases without evidence of optic nerve impingement or compression.
Methylprednisolone therapy is recommended as the initial treatment of choice because of its neuroprotective mechanism. Of the 26 eyes included in the study, all patients had received treatment with steroids. In our study, 14 eyes (53.84%) showed an improvement in VA at 1-month follow-up which was maintained during the follow-up period of 6 months. Response to steroids varies in some of the previous studies. The largest series on steroid treatment was published by the International Optic Nerve Trauma Study, which reported an improvement in 54% of the patients after 3 months of follow-up. Thirty-seven percent of the patients treated with megadose steroids in Sadeghi et al. study showed improvement after 3 months' follow-up. In the study conducted by Joseph et al., 9 of 16 patients showed a significant improvement on steroids. According to Lee et al., 91.7% of the patients treated with intravenous methylprednisolone 250 mg for 3 days, followed by oral prednisolone 1 mg/kg for 11 days, had shown at least one-line improvement of VA, and it was statistically significant (P > 0.05). Among those eyes which were treated conservatively, 77.8% had shown at least one-line improvement of VA.
Very high-dose corticosteroids limit free-radical amplification response to the trauma. The Corticosteroid Randomization after Significant Head Injury trial, a large randomized, placebo-controlled study, evaluated the effect of early administration of 48 h infusion of high-dose methylprednisolone on the risk of death and disability after head injury and found a small but statistically significant increase in the risk of death within 2 weeks after head injury in the group of corticosteroids compared with placebo (21 vs. 18) (P < 0.0001). Regarding the systemic side effects of steroids in our study, two patients developed hyperglycemia and four had mild gastrointestinal symptoms which were managed medically. Thus, the Optic Neuritis Treatment Trial (ONTT) protocol could be considered safer than high-dose steroids.
Cook et al., in a meta-analysis, reported that recovery of vision in patients treated with steroids or surgical decompression of the optic canal was significantly better than recovery in patients receiving no treatment. The same conclusion, however, has not been supported by the IONTS study which showed neither corticosteroids nor optic canal surgery is effective as the standard of care for patients with TON. Hence it was suggested that every ophthalmologist should decide to treat or not to treat on a case to case basis.
Rajiniganth et al. reported a visual improvement in 16 (70%) of 23 patients in whom treatment was started before 7 days after injury. The difference between the two groups was significant (P < 0.01). Panja et al. also showed that late initiation of therapy >7 days was associated with poor visual outcome. Yang et al. also observed a better improvement in those treated within 7 days (P = 0.056). On the other hand, Levin et al. stated that there was no indication that the dosage or timing of corticosteroid treatment or the timing of surgery was associated with an increased probability of visual improvement. In our study, among those who had early treatment, 12 out of 20 eyes (60%) improved while only 2 of the 6 eyes (33%) in the late treatment group had a significant improvement in the VA. Although this suggested a trend toward a better outcome with early initiation of therapy, the result did not attain statistical significance (P = 0.365) [Table 1]. This could probably be due to the limited number of patients included in the study. In our study, eight patients had shown an improvement in visual outcome within 1 week of initiation of therapy and six eyes more showed an improvement in VA at 1-month follow-up, and thereafter, none of the eyes improved. Two patients deteriorated at the end of 3 months. In the study conducted by Sadeghi et al., VA improved by one line in eight eyes (28.6%) immediately after treatment and in ten eyes (37%) after 3 months.
|Table 1: Visual outcome of patients based on the initiation of treatment|
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The significant prognostic factors observed in this study were degree of initial visual loss and the presence of brain contusions. In our study, patients who had an IVA >6/60 had a better visual outcome (70.58%) compared to those with an IVA < 6/60 (22.22%), and the result was statistically significant (P = 0.038) [Table 2]. Yang et al. revealed that initial visual acuity (IVA) was a statistically significant factor affecting the outcome of TON (P = 0.006). According to Chen et al., patients with initial vision better than light perception benefitted more from treatment than the patients with no light perception. Wang et al. also showed that initial VA better than light perception was associated with better outcomes (100% vs. 27%, P < 0.05).
The second statistically significant factor affecting the outcome identified in our study is the presence of brain contusions, and it was associated with poor visual outcomes (83.33% vs. 35%).
A study done by Carta et al. showed that age >40 years is a significant risk factor (RR = 1.79) for poor outcome in patients with TON. They speculate that recovery of vision in such patients may be impaired by age-related axonal lipoperoxidation and membrane hydrolysis occurring after the trauma. However, studies conducted by Wang et al. and Rajiniganth et al. did not show any significant difference in prognosis based on age. In our study, the mean age of the patients who had good visual outcome was 35.2 years compared to 37.4 years in the group that had a poor visual outcome which was not statistically significant (P = 0.562). Carta et al. reported that loss of consciousness associated with TON and the absence of recovery of VA after 48 h of steroid therapy were poor prognostic factors. Our study also showed a similar trend that a history of unconsciousness is a predictor of poor visual outcomes (66.6% vs. 33.4%). However, the result was not statistically significant (P = 0.41) [Table 3].
| Conclusions|| |
The pathogenesis of TON is inconclusive, with various possible mechanisms causing the visual loss. The management of TON is decided mainly on the basis of personal preference. Based on this study, we suggest that selected patients will benefit from corticosteroids and the ONTT protocol is safe with minimal adverse reactions.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Miller NR, Walsh FB, Hoyt WF, editors. Walsh and Hoyt's Clinical Neuro-Ophthalmology. Philaldelphia: Lippincott Williams & Wilkins; 2005;2:2380.
Yu-Wai-Man, P, Griffiths PG. Steroids for traumatic optic neuropathy. Cochrane Database of Systematic Reviews 2013.
Sadeghi TA, Lasheyei A, Tabassi A. Visual outcome of traumatic optic neuropathy in patients treated with intravenous megadose of steroids.” ACTA MEDICA IRANICA 2005;43:110-4.
Lee KF, Muhd Nor NI, Yaakub A, Wan Hitam WH. Traumatic optic neuropathy: A review of 24 patients. Int J Ophthalmol 2010;3:175-8.
Yu-Wai-Man P. Traumatic optic neuropathy-clinical features and management issues. Taiwan J Ophthalmol 2015;5:3-8.
] [Full text]
Chou PI, Sadun AA, Chen YC, Su WY, Lin SZ, Lee CC. Clinical experiences in the management of traumatic optic neuropathy. Neuro Ophthalmol 1996;16:325-36.
Levin LA, Beck RW, Joseph MP, Seiff S, Kraker R. The treatment of traumatic optic neuropathy: The International Optic Nerve Trauma Study. Ophthalmology 1999;106:1268-77.
Joseph MP, Lessell S, Rizzo J, Momose KJ. Extracranial optic nerve decompression for traumatic optic neuropathy. Arch Ophthalmol 1990;108:1091-3.
Bracken MB. CRASH (Corticosteroid Randomization after Significant Head Injury Trial): Landmark and storm warning. Neurosurgery 2005;57:1300-2.
Cook MW, Levin LA, Joseph MP, Pinczower EF. Traumatic optic neuropathy. A meta-analysis. Arch Otolaryngol Head Neck Surg 1996;122:389-92.
Rajiniganth MG, Gupta AK, Gupta A, Bapuraj JR. Traumatic optic neuropathy: Visual outcome following combined therapy protocol. Arch Otolaryngol Head Neck Surg 2003;129:1203-6.
Panja S, Gupta A, Gupta A, Prabhakar S. Determinants of outcome in traumatic optic neuropathy. Otolaryngol Head Neck Surg 2010;143 2 Suppl: P128.
Yang WG, Chen CT, Tsay PK, de Villa GH, Tsai YJ, Chen YR. Outcome for traumatic optic neuropathy-surgical versus nonsurgical treatment. Ann Plast Surg 2004;52:36-42.
Chen HY, Tsai RK, Wang HZ. Intravenous methylprednisolone in treatment of traumatic optic neuropathy. Kaohsiung J Med Sci 1998;14:577-83.
Wang BH, Robertson BC, Girotto JA, Liem A, Miller NR, Iliff N, et al
. Traumatic optic neuropathy: A review of 61 patients. Plast Reconstr Surg 2001;107:1655-64.
Carta A, Ferrigno L, Salvo M, Bianchi-Marzoli S, Boschi A, Carta F. Visual prognosis after indirect traumatic optic neuropathy. J Neurol Neurosurg Psychiatry 2003;74:246-8.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]