Possible Beneficial Effects Of Combined Fluoxetine And Occlusion Therapy In Improving And Maintaining Vision In Amblyopia Using Optical Coherence Tomography Angiography (OCTA) And Visual Evoked Potential (VEP)
Phase: NA
Conditions: Amblyopia, VEP
Sponsor: Minia University

 
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Cover Letter
 
To: editor of clinical trial 
 
Topic: Cover letter for Submission of protocol for registration in clinical trial.
 
Dear Sir/Madam, 
I wish to register an article entitled “Possible Beneficial Effects Of Combined 
Fluoxetine And Occlusion Therapy In Improving And Maintaining Vision In 
Amblyopia Using Optical Coherence Tomography Angiography (OCTA) And 
Visual Evoked Potential (VEP)”  
This article is co-authored by: 
1- Alyaa Abdelfattah Abdelmonaem Gad 
2- Ahmed Shawkat Mohamed 
3- Asmaa Anwer Mohamed 
4- Amr Ahmed Mohamed  
All authors have contributed significantly and all are in agreement with the content of the 
manuscript. 
The authors declare that there is no conflict of interests regarding the publication of this article. 
5- On behalf of all contributors, I’m Alyaa Abdelfattah Abdelmonaem Gad, will correspond 
with the journal from this point onward. 
Thank you, 
Yours’ sincerely, 
Corresponding author: 
Alyaa Abdelfattah Abdelmonaem Gad, MD, Department of Ophthalmology, Faculty of Medicine, 
Minia University, Egypt. 
Current Address: Ophthalmology Department, Faculty of Medicine, Minia University, 61511 
Minia, Egypt 
 
alyaa_medicine@yahoo.com
 
mail(s):
-
E
 
Tel.: (+2): +2 01097814574 
 
 
 
 
 
 
 
 
 
 

 
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Minia University  
Faculty of medicine 
Title
 
 
Possible Beneficial Effects Of Combined Fluoxetine And 
Occlusion Therapy In Improving And Maintaining Vision In 
Amblyopia Using Optical Coherence Tomography Angiography 
(OCTA) And Visual Evoked Potential (VEP)
 
 
 
Protocol of Thesis Submitted to 
the Faculty of Medicine
 
Minia University
 
In Partial Fulfillment of the 
requirement for(M.Sc.)Degree 
in Ophthalmology By:
 
Alyaa Abdelfattah 
Abdelmonaem Gad
 
M.B.B.Ch
 
Lecturer of Pharmacology
 
Faculty of Medicine, Minia 
University
 
 
 
 
 
           
  

 
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:
Supervisors
 
 
Prof/  Ahmed Shawkat Mohamed
 
 Professor of Ophthalmology
 
Faculty of Medicine, Minia University
 
Dr/ Asmaa anwer Mohamed
 
Associate professor of Ophthalmology
 
 
Faculty of Medicine, Minia University
 
 
Dr/ Amr Ahmed Mohamed
 
Lecturer of Ophthalmology
 
 
 Faculty of Medicine, Minia University 
 

 
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Introduction
 
Amblyopia is described as a limitation of the visual function of one or both 
eyes with no pathological cause, with a prevalence of about 1–5% of the total world 
population. This disorder is caused by early abnormal visual experience with a 
functional imbalance between the two eyes owing to anisometropia, strabismus, 
congenital cataract and ptosis, resulting in a dramatic loss of visual acuity (VA) in an 
apparently healthy eye (Baroncelli, and Maffei, 2011) . 
Clinically, amblyopia can be defined as the presence in one or both eyes of a 
VA of 6/12 or worse, with one or more lines of difference in VA between eyes in 
unilateral amblyopia which cannot be improved by refractive correction. This 
condition is an alteration of the visual cortex function which is due to suppression 
and deprivation of one eye leading to unilateral visual deterioration (Milla, and 
Piñero, 2020) . 
Optical coherence tomography (OCT) is a noninvasive technique that can 
reveal morphology of the retinal layers in vivo. OCT determines structural changes in 
the macula that may be correlated with measures of subjective visual function such as 
visual acuity and visual field (Bachmann et al., 2006). OCT angiography (OCTA) 
can provide vascular system visualization of the posterior segment in amblyopic eyes 
(Lu et al., 2022).  
Visual evoked potentials (VEPs) are a non-invasive technique routinely used in 
clinical and preclinical practice. VEPs allow to quantify the functional integrity of the 
visual system from the retina via the optic nerves, optic tracts, to the thalamus, and 
form projections to the visual cortices (Marenna et al., 2023). 
In strabismic and anisometropic amblyopia, VEP responses are reduced. VEP 
may be used as an alternative objective method for diagnosis and monitoring of 
amblyopia (Moschos et al., 2010) . 
Passive treatments such as occlusion, optical and/or pharmacological 
penalization, and Bangerter foils have been demonstrated to be potentially useful 
treatments for amblyopia. Researches are being done on new pharmacological 

 
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options to improve and maintain VA after occlusion treatment in amblyopia (Milla, 
and Piñero, 2020) . 
Adults with amblyopia cannot be treated because their brains do not have 
enough plasticity. However, results obtained both in clinical trials and in animal 
models have challenged this traditional view, unmasking a previously unsuspected 
potential for promoting recovery after the end of the critical period for visual cortex 
plasticity. These studies point toward the intracortical inhibitory transmission as a 
crucial brake for therapeutic rehabilitation and recovery from amblyopia in the adult 
brain (Baroncelli, and Maffei, 2011) . 
Selective serotonin reuptake inhibitors (SSRIs) increase serotonin activity in 
the brain. While they are mostly known for their antidepressant properties, they have 
been shown to improve visual functions in amblyopia and impact cognitive functions 
ranging from attention to motivation and sensitivity to reward (Gacoin, and Ben 
Hamed., 2023) . 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Aim of Study
 
To evaluate possible beneficial effects of fluoxetine on improving and maintaining 
visual function in amblyopia in different age groups using VA,  OCTA and VEP. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Patients and Methods 
Study design : 
A prospective clinical non-randomized comparative controlled study . 
Ethical considerations : 
All subjects included in this study will be counseled about the details and the 
nature of the study and will be required to sign a written consent. Ethical approval 
will be obtained from the local Ethics Committee of Minia University Faculty of 
Medicine before commencement of the study. The study will be conducted in 
Ophthalmology Department, Minia university Hospital, Egypt . 
Study population : 
Study participants will be recruited from the ophthalmology outpatient clinics 
of Minia University Hospitals. Imaging will be performed in the Department of 
Ophthalmology, Minia University Hospital. 
Study will include 75 eyes that will be divided into 3 groups : 
Group A: normal eyes of age-matched controls . 
Group B: amblyopic eyes treated with patching. 
Group C: amblyopic treated with patching and flouxetine . 
Inclusion Criteria : 
Patients with unilateral amblyopia  > 10 years old. 
Exclusion criteria : 
• Ocular pathology: media opacity, uveitis, glaucoma, retinal or optic nerve 
diseases,  and history of ocular trauma . 
• Poor fixation. 
• Lack of cooperation. 
• Any psychological disorder . 
Ophthalmologic Evaluation : 
All patients will undergo a thorough ocular and systemic history taking, as well 
as a comprehensive ophthalmic examination before, 3 months after patching and 
fluoxetine therapy and 3 months after therapy withdrwal, including : 
• Measurement of uncorrected and best-corrected Snellen visual acuity . 

 
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• Assessment of pupillary reflex . 
• Anterior segment slit-lamp examination . 
• Intraocular pressure (IOP) measurement using Goldmann applanation 
tonometry (GAT) . 
• Fundus examination using both binocular indirect ophthalmoscopy (BIO) and 
slit-lamp biomicroscopy with a +78 D noncontact lens . 
Ophthalmic Imaging 
Ophthalmic imaging will be performed for all patients before, 3 months after 
patching and fluoxetine therapy and 3 months after therapy withdrwal. Spectral-
domain OCTA imaging will be done using the Avanti RTVue-XR system (Optovue, 
Fremont, CA, USA) which utilizes a split-spectrum amplitude-decorrelation 
angiography (SSADA) algorithm to extract OCTA information. 
The machine has a light source centered on 840 nm with a bandwidth of 50 
nm. It is capable of an A-scan acquisition rate of 70,000 scans/second allowing for an 
axial resolution of 5 µm and a horizontal resolution of 20 µm. Each OCTA volume 
contains 304 x 304 A-scans. Two consecutive B-scans are obtained at each fixed 
location before proceeding to the next position . 
In order to minimize motion artifacts, 2 orthogonal OCTA volumes are 
acquired to perform motion correction. The Angio Retina protocol will be used for 
OCTA image acquisition. Evaluated parameters will include measurement of the 
foveal avascular zone (FAZ) and vessel density (VD) at the levels of the superficial 
capillary plexus (SCP) and deep capillary plexus (DCP) of the macula, as well VD of 
the choriocapillaris. 
 
Flash VEP (FVEP) and pattern VEP (PVEP) 
Ophthalmic functional assessment by FVEP and PVEP will be performed for all 
patients before, 3 months after patching and fluoxetine therapy and 3 months after 
therapy withdrwal. FVEP and PVEP will be done using the (Roland Consult 
supercolor Ganzfeld Q450 SC).  
 

 
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FVEP Ganzfeld 
Requirement : 
- Light-adapted patient (photopic conditions) 
- Pupils non dilated 
- 3 x EEG-Electrodes at channel 1  
- One eye covered with Impedance < 10 kOhm 
PVEP 
Requirement : 
- Distance patient → monitor: 100 cm 
- Light-adapted Patient (photopic conditions) 
- Patient refraction / correction for 100 cm viewing distance 
- 3x EEG-Electrodes at channel 1 One eye covered 
- Impedance < 10 kOhm 
Outcome Measures 
1. Comparison of VA between 3 groups . 
2. Comparison of vessel density (VD) of FAZ, superficial capillary plexus (SCP), 
deep capillary plexus (DCP) and choriocapillaris (CC) between 3 groups in 
OCTA . 
3. Comparison of FVEP and PVEP between 3  groups: 
-FVEP: latency and amplitude of P2. 
-PVEP: latency and amplitude of P100. 
Statistical Analysis: 
• Results will be analyzed using IBM SPSS. 
• P value < 0.05 will be considered significant. 
 
 
 
 
 
 

 
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References 
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coherence tomography for full range probing with high  axial resolution. Opt 
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Baroncelli L, Maffei L, Sale A. (2011): New perspectives in amblyopia therapy on 
adults: a critical role for the excitatory/inhibitory balance. Front Cell Neurosci.  24;5-
25.  
Gacoin M, Ben Hamed S. (2023): Fluoxetine degrades luminance perceptual 
thresholds while enhancing motivation and reward sensitivity. Front Pharmacol.  
20;14-1103999.  
Lu H, Zhang T, Yue T, Li X, Ma B, Liu H. (2022): Analysis of Optic Nerve in 
Adults With Amblyopia Using OCTA. Front Med (Lausanne).  14;9-903228.  
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E. (2010): Multifocal visual evoked potentials in amblyopia due to anisometropia. 
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