Extended Abstract

Introduction
Amblyopia refers to neurodevelopmental defects in the immature visual system caused by abnormal visual experiences during early life, often due to strabismus, refractive error, or visual deprivation. Treatment typically involves removing any visual axis obstruction, such as cataracts, correcting any significant refractive error, and encouraging the use of the amblyopic eye by restricting use of the better eye. The duration of treatment depends on the severity of amblyopia, the chosen treatment approach and intensity, adherence to treatment, and the patient’s age. The maximum age for effective treatment is generally considered to be 8 to 10 years, with poorer outcomes reported beyond this age. While the plasticity of the visual cortex persists beyond the typical treatment age for amblyopia, it usually does not respond to conventional treatments. Repetitive Transcranial Magnetic Stimulation (rTMS) involves applying a magnetic field to the surface layers of the cerebral cortex, inducing small electrical currents locally. TMS utilizes magnetic fields to indirectly induce localized electrical currents in the brain, thereby triggering the firing of functional neural circuits, which in turn can lead to observable behavioral effects. When pulses are repeated at regular intervals (rTMS), more enduring effects can be produced. The mechanisms underlying the sustained effects of TMS are thought to be related to neural plasticity and alterations in synaptic efficacy. This study was conducted to determine the effect of rTMS on the treatment of treatment-resistant amblyopia in adult patients.
Methods
This clinical trial was conducted on 16 patients (12 males and 4 females) with unilateral amblyopia, with a mean age of 30±5 years. The amblyopic eye was considered the intervention group, and the healthy eye served as a control.
Inclusion criteria included patients with one healthy eye and one eye with any type of amblyopia (refractive, strabismic, or mixed), aged 18 years or older, and a history of previous amblyopia treatment. A difference of at least two lines on the Snellen chart between the two eyes in unilateral cases, as well as a visual acuity less than 0.5 in bilateral cases, was considered the amblyopic eye. Patients underwent comprehensive ophthalmological examinations, including visual acuity using the E chart (Mediz, Korea) at a distance of 6 meters, determination of refractive error with and without cycloplegic drops, pupil examination, and assessment of contrast sensitivity using the CSV1000 chart (Mediz, Korea). Eye movement examinations, slit lamp examination, and funduscopy with mydriatic drops were also performed. Patients underwent rTMS on the same day. Repetitive transcranial magnetic stimulation was applied to the visual cortex using a phosphene coil near the occipital pole, which was identified individually for each patient, at a spatial frequency of 10 Hz for 15 minutes without anesthesia or sedation by a trained technician under the supervision of a psychiatrist. On the morning following the procedure, the patient’s visual acuity and contrast sensitivity were reassessed, and changes in visual acuity and contrast sensitivity compared to before rTMS were evaluated. Visual acuity and contrast measurements were taken by an experienced optometrist who was blinded to the study and repeated by another optometrist. The mean value of the two measurements was recorded as the final value.
Repetitive transcranial magnetic stimulation treatment was performed in four sessions with two-week intervals. Visual acuity and contrast sensitivity were measured at three time points: Before rTMS, after the first session of the intervention, and after the fourth session of the intervention.
Results
The highest and lowest best-corrected visual acuity of the amblyopic eye at baseline were 7/10 and 1/100, respectively, while the highest and lowest contrast sensitivity of the amblyopic eye at baseline were 3.35 and 0.91, respectively.
The mean visual acuity (Snellen line) at baseline (0.36±0.19) was not significantly different from the first treatment session (0.41±0.1); however, it showed a significant increase compared to the fourth session (0.45±0.23) (P<0.04).
The mean contrast sensitivity (cycles per decibel: cpd) at baseline (2.02±0.74) was not significantly different from the first treatment session (1.97±0.63) or the fourth session (2.16±0.94).
Conclusion
Based on the results of this study, no improvements in vision and contrast were observed in most follow-ups of patients with amblyopia after visual cortex stimulation with electromagnetic waves. Although there was an improvement in the mean vision and contrast values, it was not statistically significant, and only an improvement in vision was observed in the last follow-up compared to the baseline in the amblyopic patient group.
The use of rTMS to stimulate the visual cortex and increase blood flow to that area is with the hope of restoring visual function. There are limited studies on the role of this method in the treatment of eye diseases, which are mainly related to its role in the treatment of amblyopia.
In the present study, the measurement of visual acuity and contrast was performed the day after treatment, and only one treatment frequency was used. The reason for the lack of significant improvement in vision and contrast in our study patients may be due to the transient effects of brain stimulation.
Generally, amblyopia is not treated after the age of 10, and patch therapy is not considered an effective treatment at this age; however, it can be effective in adults due to the preservation of some brain plasticity properties, if there is no history of previous treatment. The site of functional impairment in amblyopia is in the visual cortex, and the vast majority of cortical neurons are binocular.
Repetitive transcranial magnetic stimulation has been identified as a safe and non-invasive method for stimulating the human brain. Repetitive transcranial magnetic stimulation likely affects the cortical processing of the amblyopic and healthy eyes differently with different levels of excitation and inhibition.
This treatment method is not recommended for patients, but its introduction as a new method for treating amblyopia may pave the way for studies in the field of other visual problems with a brain and neurological origin.
Ethical Statement
This study was approved by the Research Ethics Committees of Mashhad University of Medical Sciences (IR.MUMS.FM.REC.1396.102) and the Iranian Registry of Clinical Trials (IRCT20171102037171N1).
Funding
This article has been extracted from the thesis of Dr. Javad Mazloom Khorasani, submitted in partial fulfillment of the requirements for a residency degree in Ophthalmology from the School of Medicine, Mashhad University of Medical Sciences.
Conflicts of Interest
No conflict of interest.

Key message: Following the implementation of rTMS for the treatment of treatment-resistant amblyopia in older ages, no significant improvement was observed in visual acuity and contrast sensitivity in most follow-ups.