Levodopa/Carbidopa to Augment the Treatment of Amblyopia: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature on the use of levodopa/carbidopa to augment the treatment of amblyopia. METHODS: Literature searches for English language studies were last conducted in October 2022 in the PubMed database with no date restrictions. The combined searches yielded 55 articles, of which 23 were reviewed in full text. Twelve of these were considered appropriate for inclusion in this assessment and were assigned a level of evidence rating by the panel methodologist. Nine studies were rated level I, and 3 studies were rated level II; there were no level III studies. RESULTS: The duration of treatment was limited to 3 to 16 weeks because of concern about long-term adverse effects such as tardive dyskinesia. This complication was not reported in any of the study participants. The dose of levodopa ranged from 1.5 to 8.3 mg/kg/day, generally divided into 3 daily doses. The carbidopa dose was approximately 25% of the levodopa dose in all treatments. Evidence from these studies indicates that augmenting traditional patch occlusion therapy with the oral administration of levodopa/carbidopa can improve the vision of amblyopic children, but the effect was small (0.17-0.3 logarithm of the minimum angle of resolution [logMAR] units) and only statistically significant when compared with patching alone in 2 of the 12 studies cited. Regression of vision was reported in the majority of studies (9 of 12 reported; range, 0-0.17 logMAR unit regression) after discontinuation of therapy. Short-term side effects of the medications were not consistently reported but were most frequently mild and included headache and nausea. CONCLUSIONS: The best available evidence is currently insufficient to show that augmenting amblyopia therapy using up to 16 weeks of levodopa/carbidopa will result in meaningful improvement in visual acuity. Given the potential for significant side effects such as tardive dyskinesia with long-term therapy, levodopa/carbidopa does not appear to be a viable option for amblyopia therapy FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Durable recovery from amblyopia with donepezil.

An elevated threshold for neuroplasticity limits visual gains with treatment of residual amblyopia in older children and adults. Acetylcholinesterase inhibitors (AChEI) can enable visual neuroplasticity and promote recovery from amblyopia in adult mice. Motivated by these promising findings, we sought to determine whether donepezil, a commercially available AChEI, can enable recovery in older children and adults with residual amblyopia. In this open-label pilot efficacy study, 16 participants (mean age 16 years; range 9-37 years) with residual anisometropic and/or strabismic amblyopia were treated with daily oral donepezil for 12 weeks. Donepezil dosage was started at 2.5 or 5.0 mg based on age and increased by 2.5 mg if the amblyopic eye visual acuity did not improve by 1 line from the visit 4 weeks prior for a maximum dosage of 7.5 or 10 mg. Participants < 18 years of age further patched the dominant eye. The primary outcome was visual acuity in the amblyopic eye at 22 weeks, 10 weeks after treatment was discontinued. Mean amblyopic eye visual acuity improved 1.2 lines (range 0.0-3.0), and 4/16 (25%) improved by ≥ 2 lines after 12 weeks of treatment. Gains were maintained 10 weeks after cessation of donepezil and were similar for children and adults. Adverse events were mild and self-limited. Residual amblyopia improves in older children and adults treated with donepezil, supporting the concept that the critical window of visual cortical plasticity can be pharmacologically manipulated to treat amblyopia. Placebo-controlled studies are needed.

Comparison of long-term treatment outcomes of laser and anti-VEGF therapy in retinopathy of prematurity: a multicentre study from J-CREST group.

OBJECTIVES: To compare real-world, long-term outcomes of laser and anti-vascular endothelial growth factor (VEGF) therapies in patients with retinopathy of prematurity (ROP). METHODS: This was a multicentre retrospective study. We included 264 eyes of 139 patients treated for type 1 ROP or aggressive ROP (AROP) who were followed for at least 4 years. Laser treatment was initially performed in 187 eyes (the laser group), and anti-VEGF therapy was initially performed in 77 eyes (the anti-VEGF group). We collected data on sex, birth characteristics, zone, stage, and the presence of plus disease at the time of treatment and best-corrected visual acuity (BCVA), spherical equivalent (SE), and ocular complications (amblyopia and strabismus) in patients aged 4-6 years. We investigated the associations between treatment outcomes (BCVA, SE and the presence of amblyopia and strabismus) and influencing factors, including treatment procedure (anti-VEGF or laser therapy), sex, birth characteristics, zone, stage, and the presence of plus disease, using multivariable analysis and logistic regression analyses. RESULTS: The initial treatment procedure was not associated with any specific treatment outcome. Subgroup analysis of patients with zone I ROP revealed that the anti-VEGF-treated eyes had significantly better BCVA and higher SE than laser-treated eyes (p = 0.004, p = 0.009, respectively). Female patients presented significantly better BCVA, less amblyopia and less strabismus than male patients (p < 0.001, p = 0.029, p = 0.008, respectively). CONCLUSIONS: In zone I ROP, anti-VEGF therapy led to better visual acuity and less myopic refractive error than laser treatment.

Bifocal use in hyperopic anisometropic amblyopia treated with atropine: a proof-of-concept randomized trial.

OBJECTIVES: To investigate the effect of bifocal wearing in the amblyopic eye when atropine is used in the sound eye for the treatment of hyperopic anisometropic amblyopia. METHODS: Children 4-8 years old were randomly assigned to bifocal + atropine (n = 16) or only atropine (control, n = 19) groups of treatment in a proof-of-concept study. Measurements included visual acuity (logMAR), prism and cover test, stereoacuity (Randot preschool or Randot circles), contrast sensitivity (MARS test), accommodation (Grand Seiko WAM5500 and dynamic retinoscopy), retinoscopic and subjective refraction, before starting treatment and at 6 months, except accommodation, which was remeasured at 9-11 months. Main outcome measure was change in logMAR lines of visual acuity, and secondary outcome measures were change in stereoacuity and contrast sensitivity in the amblyopic eye, at 6 months. RESULTS: Improvement in visual acuity of the amblyopic eye was significantly better (p = 0.04) in the atropine plus bifocal (3.3 ± 0.9 logMAR lines) than in the atropine only group (2.6 ± 0.8 logMAR lines), whereas change in stereoacuity and contrast sensitivity was not significantly different between the two groups. Differences in accommodative gain, which was impaired in the amblyopic compared to the sound eye, before treatment, decreased after treatment, in the atropine group (0.62 ± 0.16 vs 0.79 ± 0.2, p = 0.3), and atropine + bifocal group (0.69 ± 0.15 vs 0.82 ± 0.2, p = 0.4). CONCLUSIONS: Use of bifocal lens add in the amblyopic eye of children with hyperopic anisometropic amblyopia, treated by atropine penalization, is beneficial in the follow-up period of 6 months.

Factors Influencing the Success of Atropine Penalization Treatment in Amblyopia Patients Non-Responsive to Occlusion Treatment.

PURPOSE: To evaluate the efficacy of atropine penalization after non-response to patch therapy in amblyopic children and investigate the factors associated with treatment success. PATIENTS AND METHODS: In this retrospective study, 26 children with amblyopia who were non-responders to patch therapy who were then switched to 1% atropine eye drops in the sound eye for a minimum follow-up of one year were included. All patients underwent detailed eye examinations, including optical coherence tomography and fundus autofluorescence (FAF) imaging. Response to treatment was defined as a two-line improvement in best-corrected visual acuity (BCVA) in the amblyopic eye, and patients were divided into two groups: the responder group and the non-responder group. Demographic and clinical parameters were compared between the two groups. The average central macular thickness and FAF were analyzed. RESULTS: Sixteen of 26 patients (61.5%) showed treatment response. The mean age of the patients was 10.62 ± 3.42 (5-17) years. There was no difference between the groups in age, age at start of patch therapy, sex, follow-up period, refractive errors, type of amblyopia, reason for patch therapy non-response, or mean effective patching time per day. In the responder group, the LogMAR values of pretreatment BCVA, BCVA after optical correction, and BCVA after occlusion were significantly higher, but BCVA after atropine treatment showed no difference. FAF images of all patients were normal, and the mean central macular thickness did not significantly differ between the groups. CONCLUSIONS: Atropine penalization can improve BCVA in children with amblyopia who are non-responders to patch therapy. Atropine penalization may be more successful in children with poor BCVA at the start of atropine penalization in the amblyopic eye. The results of FAF imaging and mean central macular thickness were not associated with treatment outcomes.

Effectiveness of citicoline in pediatric patients with refractive amblyopia in Surabaya, East Java, Indonesia.

OBJECTIVES: Amblyopia is a decrease of visual acuity that cannot be attributed to any structural abnormality of the eye or visual system, causing a partial or complete loss of vision due to inadequate stimulation in early life. Citicoline has been reported to improve visual acuity in amblyopic eyes as adjuvant treatment. This study was aimed to determine the effectiveness of citicoline in pediatric patients with refractive amblyopia in ophthalmology daily practices. METHODS: This was a retrospective-descriptive study with a time limited sampling method. This study was conducted at Surabaya Eye Clinic, East Java, Indonesia, by reviewing medical records for the period of January 2018 to December 2019. RESULTS: A total of 34 eyes were included in the study with the majority aged five years (41.2%) and six years (35.3%). The severity of amblyopia varied among patients, 21 eyes (61.76%) had mild amblyopia, seven eyes (20.59%) had moderate amblyopia, and two eyes (5.88%) had severe amblyopia. The duration of given therapy also varied, 18 eyes (52.94%) were given 3 months therapy, two eyes were given 4 months therapy, 12 eyes were given 6 months therapy, and two eyes were given 8 months therapy. Citicoline was found effective in mild and moderate amblyopia and for the duration of 3 and 6 months (p<0.05). In others group who did not showed statistically significant improvement was due to inadequate samples but clinically significant improvement was noted. CONCLUSIONS: Citicoline therapy resulted in a clinically and statistically improvement in refractive amblyopia patients.

Prediction of cycloplegic refraction for noninvasive screening of children for refractive error.

Detection of refractive error in children is crucial to avoid amblyopia and its impact on quality of life. We here performed a retrospective study in order to develop prediction models for spherical and cylinder refraction in children. The enrolled 1221 eyes of 617 children were divided into three groups: the development group (710 eyes of 359 children), the validation group (385 eyes of 194 children), and the comparison group (126 eyes of 64 children). We determined noncycloplegic and cycloplegic refraction values by autorefractometry. In addition, several noncycloplegic parameters were assessed with the use of ocular biometry. On the basis of the information obtained from the development group, we developed prediction models for cycloplegic spherical and cylinder refraction in children with the use of stepwise multiple regression analysis. The prediction formulas were validated by their application to the validation group. The similarity of noncycloplegic and predicted refraction to cycloplegic refraction in individual eyes was evaluated in the comparison group. Application of the developed prediction models for spherical and cylinder refraction to the validation group revealed that predicted refraction was significantly correlated with measured values for cycloplegic spherical refraction (R = 0.961, P < 0.001) or cylinder refraction (R = 0.894, P < 0.001). Comparison of noncycloplegic, cycloplegic, and predicted refraction in the comparison group revealed that cycloplegic spherical refraction did not differ significantly from predicted refraction but was significantly different from noncycloplegic refraction, whereas cycloplegic cylinder refraction did not differ significantly from predicted or noncycloplegic values. Our prediction models based on ocular biometry provide estimates of refraction in children similar to measured cycloplegic spherical and cylinder refraction values without the application of cycloplegic eyedrops.

The use of atropine for treatment of amblyopia using the OptumLabs Data Warehouse.

Atropine and patching are standard treatments for amblyopia, but the prevalence of atropine therapy in the United States is unknown. This study used the OptumLabs Data Warehouse to evaluate pharmacy claims for topical atropine to evaluate the frequency of its treatment for amblyopia and to compare demographic factors in cohorts of amblyopic children who were and were not prescribed atropine. Overall, 55.2% of amblyopic children were prescribed atropine more than once. The children who were prescribed atropine had a higher likelihood of living in geographic regions in the South or Midwest.

An update on pharmacological treatment options for amblyopia.

Amblyopia is a common cause of visual impairment in children and young adults. The cornerstone in the management of this disorder is based on increasing visual stimulation of the amblyopic eye by occlusion, by administering atropine or by causing optical penalization of the dominant eye. All these treatment options have shown some limits in terms of efficacy, due to the suboptimal treatment adherence for the patients and the lack of long-term clinical outcomes. Moreover, although it is well known that clinical efficacy decreases with age, new evidence is suggesting that cortical plasticity can be induced also in older children. For these reasons, new treatment options are being studied, in order to extend the "treatment window" beyond the critical period also in older patients. In this review, we will discuss all the most promising novel pharmacological agents in the management of amblyopia.

Subanesthetic Ketamine Reactivates Adult Cortical Plasticity to Restore Vision from Amblyopia.

Subanesthetic ketamine evokes rapid and long-lasting antidepressant effects in human patients. The mechanism for ketamine's effects remains elusive, but ketamine may broadly modulate brain plasticity processes. We show that single-dose ketamine reactivates adult mouse visual cortical plasticity and promotes functional recovery of visual acuity defects from amblyopia. Ketamine specifically induces downregulation of neuregulin-1 (NRG1) expression in parvalbumin-expressing (PV) inhibitory neurons in mouse visual cortex. NRG1 downregulation in PV neurons co-tracks both the fast onset and sustained decreases in synaptic inhibition to excitatory neurons, along with reduced synaptic excitation to PV neurons in vitro and in vivo following a single ketamine treatment. These effects are blocked by exogenous NRG1 as well as PV targeted receptor knockout. Thus, ketamine reactivation of adult visual cortical plasticity is mediated through rapid and sustained cortical disinhibition via downregulation of PV-specific NRG1 signaling. Our findings reveal the neural plasticity-based mechanism for ketamine-mediated functional recovery from adult amblyopia.

Systematic Evaluation of Levodopa Effect on Visual Improvement in Amblyopia: A Meta-analysis.

PURPOSE: This study aims to evaluate the effectiveness of levodopa as a therapeutic drug in the treatment of children and adults with amblyopia. METHODS: We performed a systematic review and meta-analysis with randomized controlled trials of levodopa and placebo in the treatment of amblyopia. All data were identified and extracted from the PubMed, EMBASE, Cochrane libraries, and the Chinese knowledge resource integration database. RESULTS: After screening the literature and evaluating the quality, 11 studies met the criteria from 308 studies. The mean difference of LogMAR visual acuity between levodopa and the placebo group was -0.1031 (95% confidence interval, -0.11 to -0.09; P < 0.0001). The improvement of visual acuities of the subgroup of younger patients with amblyopia was significantly higher than that of the placebo group (P < 0.0001). Increasing the dosage of levodopa and prolonging the treatment can significantly improve the curative effect. CONCLUSIONS: Levodopa is effective in the treatment of amblyopia by prolonging the treatment, especially for young patients.

The Effect of Combined Patching and Citalopram on Visual Acuity in Adults with Amblyopia: A Randomized, Crossover, Placebo-Controlled Trial.

Nonhuman animal models have demonstrated that selective serotonin reuptake inhibitors (SSRIs) can enhance plasticity within the mature visual cortex and enable recovery from amblyopia. The aim of this study was to test the hypothesis that the SSRI citalopram combined with part-time patching of the fellow fixing eye would improve amblyopic eye visual acuity in adult humans. Following a crossover, randomized, double-blind, placebo-controlled design, participants completed two 2-week blocks of fellow fixing eye patching. One block combined patching with citalopram (20 mg/day) and the other with a placebo tablet. The blocks were separated by a 2-week washout period. The primary outcome was change in amblyopic eye visual acuity. Secondary outcomes included stereoacuity and electrophysiological measures of retinal and cortical function. Seven participants were randomized, fewer than our prespecified sample size of 20. There were no statistically significant differences in amblyopic eye visual acuity change between the active (mean ± SD change = 0.08 ± 0.16 logMAR) and the placebo (mean change = -0.01 ± 0.03 logMAR) blocks. No treatment effects were observed for any secondary outcomes. However, 3 of 7 participants experienced a 0.1 logMAR or greater improvement in amblyopic eye visual acuity in the active but not the placebo blocks. These results from a small sample suggest that larger-scale trials of SSRI treatment for adult amblyopia may be warranted. Considerations for future trials include drug dose, treatment duration, and recruitment challenges. This study was preregistered as a clinical trial (ACTRN12611000669998).

A randomized clinical trial using atropine, cyclopentolate, and tropicamide to compare refractive outcome in hypermetropic children with a dark iris; skin pigmentation and crying as significant factors for hypermetropic outcome.

Purpose: To evaluate the refractive outcome and influencing factors following atropine 0.5% eye-drops applied twice daily during 2 ½ days at home and two drops of cyclopentolate 1% (C+C) and one drop of cyclopentolate 1% and one drop of tropicamide 1% (C+T) applied in an outpatient clinic, in hypermetropic children with a dark iris. Methods: Double-blind randomized study including 67 3-6-year-old children receiving C+C in one eye and C+T in the other eye. Two weeks later followed by atropine 0.5% in both eyes. Primary outcome measures were: spherical equivalent (SEQ) following C+C, C+T and atropine, and secondarily SEQ with respect to sex, ethnicity, skin pigmentation (light, medium, dark) and crying. Data on atropine are divided in those with C+C (CC) or C+T (CT) as a first intervention. Results: Mean SEQ±SD for C+C, C+T, atropine-(CC) and atropine-(CT) was +1.74 ± 1.35, +1.77 ± 1.34, +2.15 ± 1.43 and +2.10 ± 1.38 diopter (D). Atropine 0.5% revealed significantly more hypermetropia than C+C and C+T; +0.41 ± 0.43, 95%CI +0.31 to +0.52D and +0.33 ± 0.39, 95%CI +0.24 to +0.34D. No significant difference was present between C+C and C+T; -0.03 ± 0.56, 95%CI -0.16 to +0.11D. Ethnicity and skin-color were strongly associated (r = 0.84, p < .001). Sex was not affecting outcomes (p = .101). Ethnicity was borderline significant (p = .049). Skin-color was a highly significant factor (p = .002). A statistical model combining intervention and skin-color, with light-pigmented subjects receiving atropine-(CC) as reference group (mean SEQ +2.61 ± 1.46D), indicated borderline significantly less hypermetropia in atropine-(CC)-dark: mean decrease (95%CI): -0.81 (-1.66 to +0.05)D and atropine-(CT)-dark -0.87 (-1.70 to -0.03)D, furthermore significantly less hypermetropia in C+C-dark: -1.15 (-1.97 to -0.32)D; C+T-dark: -1.21 (-2.03 to -0.39)D, C+C-medium: -1.02 (-1.81 to -0.24)D and C+T-medium: -0.86 (-1.64 to -0.08)D. Adding crying to the model significantly less hypermetropia was found for subjects crying in all interventions; -0.53 (-0.98 to -0.09)D. Within the interventions, with light-pigmented non-crying subjects as reference group (mean SEQ in atropine, C+C, respectively, C+T: +2.62 ± 1.41, +2.33 ± 1.20 and +2.32 ± 1.20D), showed significantly less hypermetropia in dark-pigmented crying subjects in each individual intervention: atropine -1.10 (-2.01 to -0.19), C+C -1.28 (-2.14 to -0.42) and C+T -1.34 (-2.20 to -0.48)D. For medium pigmented crying subjects this was present in atropine: -0.82 (-1.61 to -0.03)D and C+C: -0.86 (-1.68 to -0.04)D, but not in C+T: -0.58 (-1.25 to +0.09)D. Conclusions: Atropine 0.5% revealed a slight significantly higher hypermetropia. A dark-pigmented skin, especially when crying upon application, resulted in lower hypermetropia in all interventions. C+T provided clinically better results in medium pigmented crying subjects compared to C+C, and equal results compared to atropine 0.5%.

Oral fluoxetine in the management of amblyopic patients aged between 10 and 40 years old: a randomized clinical trial.

OBJECTIVE: The objective of this study is to assess the efficacy of oral fluoxetine therapy in improving the visual function of amblyopic patients aged between 10 and 40 years old. METHODS: In this double-blinded, randomized, controlled trial (IRCT2016052428046N1; registered retrospectively), 40 eligible participants with anisometropic or mixed amblyopia were randomly assigned to either fluoxetine or placebo groups. Participants with anisometropia and logMAR best spectacle-corrected visual acuity (BSCVA) worse than 0.2 logMAR in the amblyopic eye or at least a two-line of difference in the BSCVA between the fellow eyes were included. Participants with significant ocular or systemic diseases were excluded. In both groups, the better eye of each patient was patched for 4-6 h a day during the study period. Participants in the treatment group were treated with oral fluoxetine for 3 months. Change in the Snellen BSCVA (after 3 months) was regarded as the primary outcome measure. RESULTS: Data from 20 participants in the fluoxetine group and 15 participants from the placebo group were analyzed (aged 11-37 years). The magnitude of improvement in visual acuity (from baseline to 3 months after treatment) was significantly higher in the fluoxetine group (0.240 ± 0.068 logMAR; 2.4 line-gain) compared with the control group (0.120 ± 0.086 logMAR; 1.2 line-gain). CONCLUSIONS: This study suggests beneficial effects of fluoxetine in the management of adult and adolescent amblyopia.

Incidence and risk of attention-deficit hyperactivity disorder in children with amblyopia: A nationwide cohort study.

IMPORTANCE: The association between visual deficits and attention disorders has been reported but remains unproven. BACKGROUND: The objective of this study was to evaluate the risk of attention-deficit hyperactivity disorder (ADHD) in children with amblyopia. DESIGN: Population-based, cohort study. PARTICIPANTS: The dataset from the Taiwan National Health Insurance Research Database in 2000 to 2010. METHODS: A total of 6817 patients aged <18 years with newly diagnosed amblyopia were identified. Four age- and sex-matched controls without amblyopia were included for each patient, that is, 27268 controls. MAIN OUTCOME MEASURES: The primary outcome was the risk of ADHD. The secondary outcomes were age at ADHD onset and use of ADHD medication. RESULTS: During a mean observation period of 7.18 years, the incidence of ADHD per 1000 person-years was 7.02 in the amblyopia group and 4.61 in the control group (P < 0.0001). The ADHD risk in the amblyopia group was 1.81 times that in the control group (hazard ratio 1.81; 95% confidence interval 1.59-2.06). After stratification by amblyopia subtype, the greatest risk was in the deprivation type (hazard ratio 2.14; 95% confidence interval 1.56-2.92) followed by the strabismic (hazard ratio 2.09; 95% confidence interval 1.15-3.79) and refractive (hazard ratio 1.76; 95% confidence interval 1.54-2.02) types. Age at ADHD onset was younger in the amblyopia group (median 8.14 vs 8.45 years; P = 0.0096). The average duration of neuropsychiatric medication use was comparable between groups (P = 0.98). CONCLUSIONS AND RELEVANCE: The ADHD risk is higher in children with amblyopia.

Intranasal BDNF administration promotes visual function recovery in adult amblyopic rats.

Amblyopia is the most common cause of visual impairment in one eye, with a prevalence of 1-5% in the world population. While amblyopia can be efficiently treated in children, it becomes irreversible in adults, due to the decline in neural plasticity past the end of the visual cortex critical period. Accordingly, no pharmacological approaches are available to rescue visual functions in adult amblyopic subjects. We report that non-invasive intranasal infusion of BDNF increased levels of this neurotrophic factor in V1 and induced a recovery of visual acuity, ocular dominance and visual depth perception in adult amblyopic rats, both in reverse-occluded animals and in those with unrestricted binocular sight. Visual recovery was long-lasting, and was prevented by pharmacological blockade of TrkB signaling in the visual cortex. These results underscore the possibility to replace invasive BDNF central administration with a safe procedure of potential interest in a number of currently still cureless central nervous system pathologies. This article is part of the Special Issue entitled "Neurobiology of Environmental Enrichment".

Fluoxetine does not enhance the effect of perceptual learning on visual function in adults with amblyopia.

Amblyopia is a common visual disorder that is treatable in childhood. However, therapies have limited efficacy in adult patients with amblyopia. Fluoxetine can reinstate early-life critical period-like neuronal plasticity and has been used to recover functional vision in adult rats with amblyopia. We conducted a Phase 2, randomized (fluoxetine vs. placebo), double-blind, multicenter clinical trial examined whether or not fluoxetine can improve visual acuity in amblyopic adults. This interventional trial included 42 participants diagnosed with moderate to severe amblyopia. Subjects were randomized to receive either 20 mg fluoxetine (n = 22) or placebo (n = 20). During the 10-week treatment period, all subjects performed daily computerized perceptual training and eye patching. At the primary endpoint, the mean treatment group difference in visual acuity improvement was only 0.027 logMAR units (95% CI: -0.057 to 0.110; p = 0.524). However, visual acuity had significantly improved from baseline to 10 weeks in both fluoxetine (-0.167 logMAR; 95% CI: -0.226 to -0.108; p < 0.001) and placebo (-0.194 logMAR; 95% CI: -0.254 to -0.133; p < 0.001) groups. While this study failed to provide evidence that fluoxetine enhances neuroplasticity, our data support other recent clinical studies suggesting that improvement of vision can be accomplished in adults with amblyopia.

Incidence of side effects of topical atropine sulfate and cyclopentolate hydrochloride for cycloplegia in Japanese children: a multicenter study.

PURPOSE: To investigate the incidence rate and side effects of topical atropine sulfate and cyclopentolate hydrochloride for cycloplegia in children aged 15 years or under. METHODS: This prospective study had been conducted at 9 institutions between April 1, 2016 and March 31, 2017 in patients 15 years old or younger who received either atropine or cyclopentolate for refraction assessment. The investigation included patient's age, symptoms, and whether patients with side effects had any systemic diseases. RESULTS: A total of 811 patients (mean age ± SD, 4.6 ± 2.2 years) received atropine and 71 (8.8%) patients had side effects. Except in patients under two years old, 1% eye drops showed higher incidence rate of side effects than 0.5% and 0.25% eye drops. Side effects most frequently occurred following the initiation of the instillation on the first day. The symptoms included flush (29/71, 40.8%), fever (21/71, 30.0%), and both (11/71, 15.5%). A total of 2238 patients (5.7 ± 3.0 years) used cyclopentolate and 27 (1.2%) (4.0 ± 2.2 years) patients had side effects. The symptoms included drowsiness (10/27, 37.0%), red eye (4/27, 14.8%), fever (3/27, 11.1%), and flush (3/27, 11.1%). CONCLUSIONS: Atropine has a side effect incidence rate 7 times higher than the incidence rate of cyclopentolate. Flush and fever are the most common side effects of atropine and drowsiness is the main side effect of cyclopentolate. These findings should be noted when examining cycloplegic refraction to manage amblyopia and strabismus in children.