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). The Aim Of The Study Is To Evaluate Possible Beneficial Effects For Different Age Groups.

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. 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. 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. OCT angiography (OCTA) can provide vascular system visualization of the posterior segment in amblyopic eyes. 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. In strabismic and anisometropic amblyopia, VEP responses are reduced. VEP may be used as an alternative objective method for diagnosis and monitoring of amblyopia. 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 options to improve and maintain VA after occlusion treatment in amblyopia. 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. 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.

Study Design: • A prospective clinical non-randomized comparative controlled study. Ethical Consideration: All patients and control subjects included in this study were verbally briefed about the details and the nature of the study. Informed consent was obtained from all patients included in the study. The study was approved by local ethical committee of Minia University Faculty of Medicine and was adherent to the tenets of Declaration of Helsinki and the approval number was 1288/2024. 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. Ophthalmic Examination: 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:Uncorrected visual acuity (UCVA). * Best corrected visual acuity (BCVA) by Snellen's chart transformed to log MAR chart. * Manifest and cycloplegic refraction using auto refractometer (Nidek CO, Japan). * Intraocular pressure (IOP) by air puff tonometry (TOPCON computerized tonometer CT-800, Japan). * Anterior segment examination using slit-lamp bio-microscopy (Sunkingdom LS-3, Germany). * Dilated Fundus examination using slit lamp bio-microscopy using a +78 diopter condensing lens and peripheral retinal examination by means of binocular indirect ophthalmoscopy. Investigations: Ophthalmic imaging: OCT-A (Optovue Inc. Fremont, CA, USA). OCT-A technique: OCT-A scans were done using AngioVue OCTTM system on RTVue XR 100 Avanti spectral domain-OCT device, version 2015 (Optovue Inc, Fremont, CA, USA). Technique: * OCT-A was done in dim light following appropriate pupillary dilation using cyclopentolate 1% eye drops (Plegica, Hikma) and patient data were entered and the examination type was selected from the machine software. * The patient was asked to place the chin on the chin rest, forehead against the forehead rest, eye to be scanned aligned horizontally with the canthus mark, and to look inside the imaging aperture. * The patient was asked to look at the fixation target, a blue dot in the red field. * The patient's eye was placed at the center of the video picture, and the working distance between the scanning head and the patient's eye was adjusted to improve the video image. The scan head was then slowly advanced nearer till fundus image sharpened. * The scan signal strength index (SSI) was optimized to be ≥ 50. * After instructing the patient to stare at the center of the blue target, pictures were recorded by pressing the joystick or checkmark button. OCT-A print out: The print out of the gray scale angiovue retinal scan included: Across the top, four angiovue en-face images at different depths: * Superficial layer: including vasculature from the nerve layer and GCL. * Deep layer: include both intermediate and deep inner retinal vasculature. * Outer retina: lying between OPL and RPE * Choriocapillaris: include the inner layer of choroidal blood vessels At lower left, an OCT en-face image overlaid with an angiovue image that indicate the angiovue scan area. At the lower right, horizontal and vertical B scan images, each en-face angiovue image has green horizontal and red vertical lines that indicate the current B-scan location; we can drag these lines to select which horizontal and vertical B-scan display. In this study, OCT-A parameters that were compared in this study include vessel density in SCP, DCP and chorio-capillaris layers in either the whole image of central 6 mm, foveal and para-foveal regions as well as FAZ area. 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). 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: Data analyses were performed using statistical package for the social science (SPSS) software version 26. Demographic and outcome data were presented as mean± standard deviation for continuous variables with normal distribution. Categorical variables were reported as frequency (sex). Shapiro-Wilk test and Kolmogorov Simonov test were performed to test the normality of the data. One way ANOVA test was done to compare results between 3 groups and a two sided p \< 0.05 was considered as statistically significant.