Brimonidine as a possible treatment for myopia.

BACKGROUND: Myopia is becoming a huge burden on the world's public health systems. The purpose of this study was to explore the effect of brimonidine in the treatment of form-deprivation myopia (FDM) and the relationship between intraocular pressure (IOP) and myopia development. METHODS: Monocular form deprivation myopia (FDM) was induced in three-week-old pigmented male guinea pigs. They were treated with 3 different methods of brimonidine administration (eye drops, and subconjunctival or intravitreal injections). Four different concentrations of brimonidine were tested for each method (2µg/µL, 4µg/µL, 20µg/µL, and 40µg/µL). All treatments continued for a period of 21 days. Tonometry, retinoscopy, and A-scan ultrasonography were used to monitor intraocular pressure, refractive error and axial length (AL), respectively. RESULTS: Treatment with subconjunctival brimonidine at 40µg/µL, and intravitreal brimonidine at 2µg/µL and 4µg/µL, inhibited the development of FDM. The myopic refraction, excessive axial length, and elevation of IOP were significantly decreased. Brimonidine in eye drops was ineffective. CONCLUSION: Brimonidine at appropriate doses significantly reduced the development of FD myopia in guinea pigs. The IOP may change with FD myopia.

Ambient sound stimulation tunes axonal conduction velocity by regulating radial growth of myelin on an individual, axon-by-axon basis.

Adaptive myelination is the emerging concept of tuning axonal conduction velocity to the activity within specific neural circuits over time. Sound processing circuits exhibit structural and functional specifications to process signals with microsecond precision: a time scale that is amenable to adjustment in length and thickness of myelin. Increasing activity of auditory axons by introducing sound-evoked responses during postnatal development enhances myelin thickness, while sensory deprivation prevents such radial growth during development. When deprivation occurs during adulthood, myelin thickness was reduced. However, it is unclear whether sensory stimulation adjusts myelination in a global fashion (whole fiber bundles) or whether such adaptation occurs at the level of individual fibers. Using temporary monaural deprivation in mice provided an internal control for a) differentially tracing structural changes in active and deprived fibers and b) for monitoring neural activity in response to acoustic stimulation of the control and the deprived ear within the same animal. The data show that sound-evoked activity increased the number of myelin layers around individual active axons, even when located in mixed bundles of active and deprived fibers. Thicker myelination correlated with faster axonal conduction velocity and caused shorter auditory brainstem response wave VI-I delays, providing a physiologically relevant readout. The lack of global compensation emphasizes the importance of balanced sensory experience in both ears throughout the lifespan of an individual.

Daily dose-response from short-term monocular deprivation in adult humans.

Short-term monocular deprivation (MD) shifts sensory eye balance in favour of the previously deprived eye. The effect of MD on eye balance is significant but brief in adult humans. Recently, researchers and clinicians have attempted to implement MD in clinical settings for adults with impaired binocular vision. Although the effect of MD has been studied in detail in single-session protocols, what is not known is whether the effect of MD on eye balance deteriorates after repeated periods of MD (termed 'perceptual deterioration'). An answer to this question is relevant for two reasons. Firstly, the effect of MD (i.e., dose-response) should not decrease with repeated use if MD is to be used therapeutically (e.g., daily for weeks). Second, it bears upon the question of whether the neural basis of the effects of MD and contrast adaptation, a closely related phenomenon, is the same. The sensory change from contrast adaptation depends on recent experience. If the observer has recently experienced the same adaptation multiple times for consecutive days, then the adaptation effect will be smaller because contrast adaptation exhibits perceptual deterioration, so it is of interest to know if the effects of MD follow suit. This study measured the effect of 2-h MD for seven consecutive days on binocular balance of 15 normally sighted adults. We found that the shift in eye balance from MD stayed consistent, showing no signs of deterioration after subjects experienced multiple periods of MD. This finding shows no loss of effectiveness of repeated daily doses of MD if used therapeutically to rebalance binocular vision in otherwise normal individuals. Furthermore, ocular dominance plasticity, which is the basis of the effects of short-term MD, does not seem to share the property of 'perceptual deterioration' with contrast adaptation, suggesting different neural bases for these two related phenomena.

Deprivation-Induced Plasticity in the Early Central Circuits of the Rodent Visual, Auditory, and Olfactory Systems.

Activity-dependent neuronal plasticity is crucial for animals to adapt to dynamic sensory environments. Traditionally, it has been investigated using deprivation approaches in animal models primarily in sensory cortices. Nevertheless, emerging evidence emphasizes its significance in sensory organs and in subcortical regions where cranial nerves relay information to the brain. Additionally, critical questions started to arise. Do different sensory modalities share common cellular mechanisms for deprivation-induced plasticity at these central entry points? Does the deprivation duration correlate with specific plasticity mechanisms? This study systematically reviews and meta-analyzes research papers that investigated visual, auditory, or olfactory deprivation in rodents of both sexes. It examines the consequences of sensory deprivation in homologous regions at the first central synapse following cranial nerve transmission (vision - lateral geniculate nucleus and superior colliculus; audition - ventral and dorsal cochlear nucleus; olfaction - olfactory bulb). The systematic search yielded 91 papers (39 vision, 22 audition, 30 olfaction), revealing substantial heterogeneity in publication trends, experimental methods, measures of plasticity, and reporting across the sensory modalities. Despite these differences, commonalities emerged when correlating plasticity mechanisms with the duration of sensory deprivation. Short-term deprivation (up to 1 d) reduced activity and increased disinhibition, medium-term deprivation (1 d to a week) involved glial changes and synaptic remodeling, and long-term deprivation (over a week) primarily led to structural alterations. These findings underscore the importance of standardizing methodologies and reporting practices. Additionally, they highlight the value of cross-modal synthesis for understanding how the nervous system, including peripheral, precortical, and cortical areas, respond to and compensate for sensory inputs loss.

Synchronous myopia development induced by bilateral form deprivation in chicks.

Form deprivation (FD) is a widely employed experimental paradigm, typically used to induce unilateral myopia in animal models. This model is weakened by potential influence upon the FD eye from vision in the freely-viewing contralateral eye, which could be eliminated by imposing FD in both eyes; but while a few previous studies have explored the feasibility of inducing bilateral FD in chicks, substantial discrepancies in treatment outcomes were noted. Consequently, this study aimed to establish a bilateral FD myopia model in chicks, with validation by investigating the associated ocular growth patterns, feeding, and social behavior. Six-day-old chicks were treated with bilateral (n = 21) or unilateral (n = 10) FD for 12 days; the fellow untreated eyes in the unilateral FD group served as controls. Refractive error, corneal power, and ocular axial dimensions were measured at 4-day intervals after the onset of form deprivation, with a Hartinger refractometer, a custom-made videokeratography system, and a high-resolution A-scan ultrasonographer, respectively. Body weight was monitored to assess the chick's physical development. Our results showed that birds treated with bilateral FD grew as robustly as the unilaterally form-deprived chicks, with similar or slightly heavier body weights and mortalities. Unilateral FD induced significantly higher myopia in the treated eye, with stronger corneal power, deeper anterior and vitreous chambers, and longer axial length. Moreover, either bilaterally or unilaterally FD eyes developed similar refractive error (bilateral FD, left: -28.03 ± 9.06 D, right: -28.44 ± 9.45 D; unilateral FD: -29.48 ± 8.26 D) and ocular biometric changes; but choroidal thickness was thicker in bilaterally FD eyes, rather than thinner as in unilaterally FD eyes. In addition to the highly synchronized (symmetrical, parallel) development reported previously in bilateral FD, we found in this study that the correlations between bilaterally form-deprived eyes were highest for ocular biometric parameters directly contributing to myopia development, including corneal power (r = 0.74 to 0.93), anterior chamber depth (r = 0.60 to 0.85), vitreous chamber depth (r = 0.92 to 0.94), and axial length (r = 0.90 to 0.96). The remarkably synchronized growth pattern confirmed the feasibility of the bilateral FD paradigm for future research on myopia.

Supervised dichoptic gaming versus monitored occlusion therapy for childhood amblyopia: Effectiveness and efficiency.

PURPOSE: To compare the effectiveness and efficiency of supervised dichoptic action-videogame play to occlusion therapy in children with amblyopia. METHODS: Newly diagnosed children with amblyopia aged 4-12 years were recruited, excluding strabismus >30PD. After 16 weeks of refractive adaptation children were randomized to gaming 1 h/week supervised by the researcher, or electronically monitored occlusion 2 h/day. The gaming group played a dichoptic action-videogame using virtual reality goggles, which included the task of catching a snowflake presented intermittently to the amblyopic eye. Contrast for the fellow eye was self-adjusted until 2 identical images were perceived. The primary outcome was visual acuity (VA) change from baseline to 24 weeks. RESULTS: We recruited 96 children, 29 declined and 2 were excluded for language or legal issues. After refractive adaptation, 24 of the remaining 65 no longer met the inclusion criteria for amblyopia, and 8 dropped out. Of 16 children treated with gaming, 7 (6.7 years) completed treatment, whereas 9 younger children (5.3 years) did not. Of 17 treated with occlusion, 14 (5.1 years) completed treatment and 3 (4.5 years) did not. Of 5 children with small-angle strabismus, 3 treated with occlusion completed treatment and 2 treated with gaming did not. Median VA improved by 0.30 logMAR (IQR 0.20-0.40) after gaming, 0.20 logMAR (0.00-0.30) after occlusion (p = 0.823). Treatment efficiency was 1.25 logMAR/100 h (range 0.42-2.08) with gaming, 0.08 (-0.19-0.68) with occlusion (p < 0.001). CONCLUSION: Dichoptic gaming seems a viable alternative for older children with refractive amblyopia after glasses adaptation. Treatment efficiency with gaming under continuous supervision was 15 times higher than with occlusion at home.

Effectiveness of a Novel Video Game Platform in the Treatment of Pediatric Amblyopia.

PURPOSE: To test the non-inferiority of a novel game platform for the treatment of pediatric amblyopia compared to standard eye patching. METHODS: Forty participants (ages 4 to 18 years) across seven optometric clinics in the United States diagnosed as having amblyopia associated with anisometropia were randomly assigned to either 12 weeks of eye patching therapy (n = 19) or Barron Vision (Barron Associates, Inc) video game treatment (n = 21). Participants in the eye patching group with best corrected visual acuity (BCVA) worse than 20/200 in their amblyopic eye were prescribed 6 hours of patching daily, whereas those whose BCVA was 20/200 (1.00 logarithm of the minimum angle of resolution [logMAR]) or better were instructed to patch for 2 hours daily. Participants in the video game group, irrespective of the severity of their amblyopia, were instructed to play four different 5-minute mini-games five times a week for a total of 20 minutes a day. RESULTS: A mixed linear modeling analysis of before and after BCVA differences after 12 weeks showed the non-inferiority of video game treatment to eye patching using a 0.10 logMAR threshold while adjusting for the participant's age, sex, and baseline BCVA. CONCLUSIONS: The results of the study suggest that a 12-week home-based video game vision therapy intervention can provide equivalent treatment outcomes to eye patching for amblyopia in children ages 5 to 18 years. Video game-based vision therapy may be a more acceptable and time-efficient alternative to existing approaches. By incorporating elements of perceptual learning, approaches such as Barron Vision video game treatment may have additional long-term therapeutic benefits and may improve treatment compliance. [J Pediatr Ophthalmol Strabismus. 2024;61(1):20-29.].

Randomized Controlled Trial of Patching versus Dichoptic Stimulation Using Virtual Reality for Amblyopia Therapy.

Purpose: To compare the outcomes of patching to dichoptic stimulation using virtual reality (VR) in moderate and severe amblyopia.Methods: This study was conducted on 86 subjects with unilateral anisometropic and mixed amblyopia. The subjects were randomized to the VR or patching group. The VR group received treatment using the Vivid Vision software (Vivid Vision Inc., San Francisco, USA) with each subject receiving weekly 2 h-sessions for 10 weeks. The patching group was prescribed patching for 10 weeks. Best-corrected visual acuity (BCVA) was measured using a single crowded letter in an ETDRS chart before, after 10 weeks of treatment, and after another 10 weeks of cessation of treatment. Near stereoacuity was measured using the TNO test.Results: Forty-two patients were randomized to the patching group and 44 to the VR group. The median age of the subjects was 12.0 (range 6.0 to 37.0) years. In the VR group, mean amblyopic eye BCVA showed statistically significant improvement by 0.89 line (95% confidence interval {CI}, 0.73 to 1.35 lines; p < 0.001) after 10 weeks of therapy, and after another 10 weeks of follow-up by 1.32 lines from baseline (95% CI, 1.15 to 1.7 lines; p < 0.001). Regarding the patching group, mean BCVA showed statistically significant improvement after 10 weeks by 1.38 lines (95% CI, 0.82 to 1.8 lines; p < 0.001), and after another 10 weeks by 1 line from baseline (95% CI, 0.06-0.147; 0.6 to 1.47 lines; p < 0.001). There was no significant difference between both groups at any time-point (p values >0.05). No serious adverse events were noted. Adults and severe amblyopes in the VR group showed more significant VA improvement than their counterparts in the patching group.Conclusions: Amblyopes treated using VR dichoptic treatment demonstrated statistically significant VA improvement after 10 and 20 weeks of follow-up that is comparable to patching.

Impact of active vision therapy compared to conventional patching therapy on visual acuity and stereoacuity in children with amblyopia.

PURPOSE: To compare improvements in visual acuity (VA) and stereoacuity between active vision therapy (AVT) and conventional patching therapy in children with amblyopia. METHODS: This study included 65 children aged 5 to 16 years (mean age±SD, 11.00±3.29 years) with unilateral amblyopia. Among them, 31 children underwent active vision therapy (AVT group), and 34 children underwent conventional patching therapy (patching group). AVT group underwent three sequential phases of AVT: Monocular phase (pursuit, saccades, fixation, visuomotor, eye-hand coordination, and central peripheral activities), biocular phase (diplopia awareness, antisuppression, monocular fixation in a binocular field, accommodative activities, bilateral integration, and fine motor activities) and binocular phase (fusion and stereopsis). Patching group patched their fellow eyes as per guidelines by Pediatric Eye Disease Investigator Group. Best-corrected monocular VA and stereoacuity were measured at baseline and after three months of therapy in both groups. RESULTS: There were significant improvements in the mean acuities in amblyopic eye (AE) in both AVT (0.32±0.11 logMAR, p <0.001) and patching groups (0.27±0.19 logMAR, p Ë‚ 0.001). However, there was no significant difference in mean acuity gains in AE between AVT and patching groups (p = 0.059). Mean gains in stereoacuities (log seconds of arc) were statistically significant in both AVT (0.81±0.34, p < 0.001) and patching groups (0.32±0.34, p < 0.001). The stereoacuity gain in the AVT group was significantly higher compared to patching group (p < 0.001). CONCLUSION: Active vision therapy had a better impact than conventional patching therapy in terms of improvement of stereoacuity but not in terms of VA when used for treating children with amblyopia.

Expression of early growth responsive gene-1 in the lateral geniculate body of kittens with amblyopia caused by monocular form deprivation.

OBJECTIVE: The expression of early growth responsive gene-1 (Egr-1) in the lateral geniculate body in the normal kittens and those affected with amblyopia caused by monocular visual deprivation was compared to explore the potential significance of Egr-1 in the pathogenesis of amblyopia. METHODS: A total of 30 healthy kittens were equally and randomly divided into the control (n = 15) and the deprivation group (n = 15). The kittens were raised in natural light and the right eyes of the deprived kittens were covered with a black opaque covering. Pattern visual evoked potential (PVEP) was measured before and 1, 3, and 5 weeks after covering. Five kittens from each group were randomly selected and euthanized with 2% sodium pentobarbital (100 mg/kg) during the 1st, 3rd and 5th week after covering. The expression of Egr-1 in the lateral geniculate body in the two groups was compared by performing immunohistochemistry and in situ hybridization. RESULTS: After three weeks of covering, PVEP detection indicated that the P100 wave latency in the deprivation group was significantly higher than that in the control group (P < 0.05), whereas the amplitude decreased markedly (P < 0.05). The number of the positive cells (P < 0.05) and mean optical density (P < 0.05) of Egr-1 protein expression in the lateral geniculate body of the deprivation group were found to be substantially lower in comparison to the normal group, as well as the number (P < 0.05) and mean optical density of Egr-1 mRNA-positive cells (P < 0.05). However, with increase of age, positive expression of Egr-1 in the control group showed an upward trend (P < 0.05), but this trend was not noted in the deprivation group (P > 0.05). CONCLUSIONS: Monocular form deprivation can lead to substantially decreased expressions of Egr-1 protein and mRNA in the lateral geniculate body, which in turn can affect the normal expression of neuronal functions in the lateral geniculate body, thereby promoting the occurrence and development of amblyopia.

Is there value in measuring near visual acuity during occlusion therapy for amblyopia?

Introduction: The purpose of this study was to investigate near and distance visual acuity (VA) prior to, during and on completion of occlusion therapy for amblyopia. Method: Fifty-four patients aged 4-7 years (mean 4.9; ±0.44) with untreated strabismic, anisometropic or mixed amblyopia were recruited to the study following refractive adaptation where applicable. All patients underwent conventional occlusion (patching). Uniocular near and distance VA was tested using age and ability appropriate Crowded LogMAR VA tests prior to, during and upon conclusion of occlusion therapy. Results: In amblyopic eyes, there was no significant difference between near and distance VA prior to occlusion therapy with LogMAR Crowded (p = .66; mean distance VA at 3 m = 0.6 LogMAR; mean near VA at 40 cm = 0.58 LogMAR), or with LogMAR Crowded Kay Picture test (p = .78, mean distance VA at 3 m = 0.44 LogMAR; mean near VA at 33 cm = 0.46 LogMAR;). No significant difference was found between near and distance VA at any visit during occlusion therapy, or on completion of occlusion therapy with LogMAR Crowded (p = .86, mean final distance VA at 3 m = 0.266 LogMAR; mean final near VA at 40 cm = 0.25 LogMAR) or LogMAR Crowded Kay Pictures (p = .74, mean final distance VA at 3 m = 0.16 LogMAR; mean final near VA at 33 cm = 0.16 LogMAR). There was no significant difference in the VA of the fellow (non-amblyopic) eyes prior to and on completion of occlusion therapy with LogMAR Crowded at distance (3 m) or near (40 cm) (p = .05, p = .40 respectively); or with LogMAR Crowded Kay Pictures at distance (3 m) or near (33 cm) (p = .89, p = .35 respectively). Discussion: Improvement in VA of amblyopic eyes did not significantly differ between near and distance testing proximites at any point during the course of occlusion therapy for amblyopia in our study. These findings may aid clinicians with appropriate test selection and help with clinical time pressures. Where patient concentration does not allow for uniocular distance vision, uniocular near vision may be used to diagnose amblyopia, and vice versa. This could prevent delay in the treatment of amblyopia.

Active vision gates ocular dominance plasticity in human adults.

Primary visual cortex (V1) retains a form of plasticity in adult humans: a brief period of monocular deprivation induces an enhanced response to the deprived eye, which can stabilize into a consolidated plastic change1,2 despite unaltered thalamic input3. This form of homeostatic plasticity in adults is thought to act through neuronal competition between the representations of the two eyes, which are still separate in primary visual cortex4,5. During monocular occlusion, neurons of the deprived eye are thought to increase response gain given the absence of visual input, leading to the post-deprivation enhancement. If the decrease of reliability of the monocular response is crucial to establish homeostatic plasticity, this could be induced in several different ways. There is increasing evidence that V1 processing is affected by voluntary action, allowing it to take into account the visual effects of self-motion6, important for efficient active vision7. Here we asked whether ocular dominance homeostatic plasticity could be elicited without degrading the quality of monocular visual images but simply by altering their role in visuomotor control by introducing a visual delay in one eye while participants actively performed a visuomotor task; this causes a discrepancy between what the subject sees and what he/she expects to see. Our results show that homeostatic plasticity is gated by the consistency between the monocular visual inputs and a person's actions, suggesting that action not only shapes visual processing but may also be essential for plasticity in adults.

Sensory deprivation arrests cellular and synaptic development of the night-vision circuitry in the retina.

Experience regulates synapse formation and function across sensory circuits. How inhibitory synapses in the mammalian retina are sculpted by visual cues remains unclear. By use of a sensory deprivation paradigm, we find that visual cues regulate maturation of two GABA synapse types (GABAA and GABAC receptor synapses), localized across the axon terminals of rod bipolar cells (RBCs)-second-order retinal neurons integral to the night-vision circuit. Lack of visual cues causes GABAA synapses at RBC terminals to retain an immature receptor configuration with slower response profiles and prevents receptor recruitment at GABAC synapses. Additionally, the organizing protein for both these GABA synapses, LRRTM4, is not clustered at dark-reared RBC synapses. Ultrastructurally, the total number of ribbon-output/inhibitory-input synapses across RBC terminals remains unaltered by sensory deprivation, although ribbon synapse output sites are misarranged when the circuit develops without visual cues. Intrinsic electrophysiological properties of RBCs and expression of chloride transporters across RBC terminals are additionally altered by sensory deprivation. Introduction to normal 12-h light-dark housing conditions facilitates maturation of dark-reared RBC GABA synapses and restoration of intrinsic RBC properties, unveiling a new element of light-dependent retinal cellular and synaptic plasticity.

Amblyopia treatment outcomes in patients with neurodevelopmental disorders.

PURPOSE: To compare amblyopia treatment outcomes between patients with neurodevelopmental disorders and their typically developing peers. METHODS: Of 2,311 patients diagnosed with amblyopia between 2010 and 2014 at Boston Children's Hospital, 460 met inclusion criteria (age 2-12 with anisometropic, strabismic, or mixed amblyopia [interocular difference (IOD) ≥2 lines]). Treatment and visual outcomes were analyzed according to neurodevelopmental status: neurodevelopmental delay (DD) versus typical development (TD). RESULTS: The DD group (n = 54) and TD group (n = 406) were similar in demographics, amblyogenic risk factors, baseline visual measures, prescribed therapy, and adherence (P ≥ 0.10). Between-visit follow-up time was longer for the DD group (0.65 [0.42- 0.97] years) than for the TD group (0.5 [0.36-0.82] years; P = 0.023). IOD improved similarly in each group by the last visit (DD, -0.15 logMAR [-0.31 to -0.02]; TD, -0.2 logMAR [-0.38 to -0.1]; P = 0.09). Each group reached amblyopia resolution by the last visit at similar frequencies (DD, 23/54 [43%]; TD, 211/406 [52%]; P > 0.2). DD diagnosis did not independently influence amblyopia resolution (HR, 0.77; 95% CI, 0.53-1.12; P = 0.17), but each additional month of interval time between follow-up visits reduced the likelihood of resolution by 2.7% (HR, 0.67; 95% CI, 0.51-0.87; P = 0.003). CONCLUSIONS: Patients with DD and those with TD responded similarly to amblyopia therapy; however, follow-up intervals were longer in patients with DD and correlated with the likelihood of persistent amblyopia, suggesting that greater efforts at assuring follow-up may benefit patients with DD.

Metaplasticity: Dark exposure boosts local excitability and visual plasticity in adult human cortex.

An interlude of dark exposure for about 1 week is known to shift excitatory/inhibitory (E/I) balance of the mammalian visual cortex, promoting plasticity and accelerating visual recovery in animals that have experienced cortical lesions during development. However, the translational impact of our understanding of dark exposure from animal studies to humans remains elusive. Here, we used magnetic resonance spectroscopy as a probe for E/I balance in the primary visual cortex (V1) to determine the effect of 60 min of dark exposure, and measured binocular combination as a behavioural assay to assess visual plasticity in 14 normally sighted human adults. To induce neuroplastic changes in the observers, we introduced 60 min of monocular deprivation, which is known to temporarily shift sensory eye balance in favour of the previously deprived eye. We report that prior dark exposure for 60 min strengthens local excitability in V1 and boosts visual plasticity in normal adults. However, we show that it does not promote plasticity in amblyopic adults. Nevertheless, our findings are surprising, given the fact that the interlude is very brief. Interestingly, we find that the increased concentration of the excitatory neurotransmitter is not strongly correlated with the enhanced functional plasticity. Instead, the absolute degree of change in its concentration is related to the boost, suggesting that the dichotomy of cortical excitation and inhibition might not explain the physiological basis of plasticity in humans. We present the first evidence that an environmental manipulation that shifts cortical E/I balance can also act as a metaplastic facilitator for visual plasticity in humans. KEY POINTS: A brief interlude (60 min) of dark exposure increased the local concentration of glutamine/glutamate but not that of GABA in the visual cortex of adult humans. After dark exposure, the degree of the shift in sensory eye dominance in favour of the previously deprived eye from short-term monocular deprivation was larger than that from only monocular deprivation. The neurochemical and behavioural measures were associated: the magnitude of the shift in the concentration of glutamine/glutamate was correlated with the boost in perceptual plasticity after dark exposure. Surprisingly, the increase in the concentration of glutamine/glutamate was not correlated with the perceptual boost after dark exposure, suggesting that the physiological mechanism of how E/I balance regulates plasticity is not deterministic. In other words, an increased excitation did not unilaterally promote plasticity.

Risk of recurrence after cessation of dichoptic, binocular treatment of amblyopia.

Contrast-rebalanced dichoptic games and videos have been shown to be an effective treatment for childhood amblyopia. Whether the visual acuity gains achieved with these binocular treatments are long-lasting has not been determined. In this prospective cohort study of 100 consecutive amblyopic children who improved by ≥0.2 logMAR or obtained ≤0.2 logMAR amblyopic eye visual acuity during a binocular treatment clinical trial, risk of recurrence was 24% (95% CI, 16%-35%) at up to 3 years' follow-up according to Kaplan-Meier survival analysis, which accounts for censored, truncated, and missing data. Risk of recurrence was similar among children who required additional treatment for residual amblyopia after 4-8 weeks of dichoptic treatment (n = 62 [19%]; 95% CI, 10%-34%) and those who did not (n = 38 [32%]; 95% CI, 18%-52%; P = 0.12). There was no association between recurrence and age, visual acuity at the end of binocular treatment, stereoacuity, or ocular alignment. In a secondary analysis to compare rates of recurrence with published data, risk of recurrence in the subset of children who had no additional treatment for residual amblyopia (28%) was similar to the reported recurrence after cessation of successful patching and atropine (24%) at 12 months. Children with successful binocular treatment of amblyopia require monitoring for recurrence of amblyopia.

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.

Cholinergic modulation of sensory perception and plasticity.

Sensory systems are highly plastic, but the mechanisms of sensory plasticity remain unclear. People with vision or hearing loss demonstrate significant neural network reorganization that promotes adaptive changes in other sensory modalities as well as in their ability to combine information across the different senses (i.e., multisensory integration. Furthermore, sensory network remodeling is necessary for sensory restoration after a period of sensory deprivation. Acetylcholine is a powerful regulator of sensory plasticity, and studies suggest that cholinergic medications may improve visual and auditory abilities by facilitating sensory network plasticity. There are currently no approved therapeutics for sensory loss that target neuroplasticity. This review explores the systems-level effects of cholinergic signaling on human visual and auditory perception, with a focus on functional performance, sensory disorders, and neural activity. Understanding the role of acetylcholine in sensory plasticity will be essential for developing targeted treatments for sensory restoration.

Comprehensive review of amblyopia: Types and management.

The optimal method of treatment for a child depends on the patient's age at the time of diagnosis, the onset and type of amblyopia, and the degree of compliance attainable. In deprivation amblyopia, the cause of visual impairment (e.g., cataract, ptosis) needs to be treated first, and then the disorder can be treated such as other types of amblyopia. Anisometropic amblyopia needs glasses first. In strabismic amblyopia, conventionally amblyopia should be treated first, and then strabismus corrected. Correction of strabismus will have little if any effect on the amblyopia, although the timing of surgery is controversial. Best outcomes are achieved if amblyopia is treated before the age of 7 years. The earlier the treatment, the more efficacious it is. In selected cases of bilateral amblyopia, the more defective eye must be given a competitive advantage over the comparatively good eye. Glasses alone can work when a refractive component is present, but occlusion might make the glasses work faster. The gold standard therapy for amblyopia remains occlusion of the better eye although penalization is also evidenced to achieve equal results. Pharmacotherapy has been shown to achieve suboptimal outcomes. Newer monocular and binocular therapies based on neural tasks and games are adjuncts to patching and can also be used in adults.

Satisfaction and quality of life in cochlear implant users with long sensory deprivation.

PURPOSE: The aim of the study was to verify the level of satisfaction of CI users with long periods of hearing deprivation, highlighting the positive and negative aspects of the use of the device and their quality of life. METHODS: This is a analytical research, of the type observational cross-sectional study. The study was performed with 24 patients from a private Institute of Otorhinolaryngology. Three surveys were applied: Satisfaction with Amplification in Daily Life (SADL), International Outcome Inventory - Cochlear Implant (IOI - CI) to assess cochlear implant satisfaction and WHOQOL- bref to assess the quality of life. The results in the pre and post lingual groups were compared. RESULTS: The highest degree of satisfaction was reported with regard to personal image, positive effects, and how the users feel about their CI. The lowest degree of satisfaction was reported regarding the cost-benefit of the CI and the competitive noise. In the WHOQOL-bref assessment, the highest scores were found in physical, psychological and social relations domains. When comparing the results of the surveys, the pre and post-lingual groups showed no difference in relation to the achieved scores. CONCLUSION: The participants had a high level of satisfaction with the use of cochlear implants. The longer the sensory deprivation time, the greater the degree of satisfaction with the device. The use of the CI electronic device reflects on the individual's quality of life.