Landolt Ring-Shaped Epithelial Keratopathy: A Novel Corneal Disease in a Non-Japanese White Patient.

PURPOSE: Landolt ring-shaped epithelial keratopathy is a corneal disease that has only been reported in 11 Japanese patients in 2014.1 We describe the first case of Landolt ring-shaped epithelial keratopathy in the United States in a patient of European background. METHODS: This is a single case report with longitudinal care. RESULTS: A 35-year-old White patient presented with a history of ocular burning, photophobia, and decreased vision. Corneal examination showed bilateral and asymmetric microcystic lesions in a unique Landolt ring (or the letter "C") shape, distributed randomly in the epithelium. Confocal microscopy revealed cellular ballooning and hyperreflective opacities in the basal layer of the corneal epithelium. The patient has had multiple recurrences of her symptoms year-round, each lasting 4 to 8 days. Topical treatment with cyclosporine, steroids, and lubrication resolved her symptoms but without complete resolution of signs on examination. CONCLUSIONS: Our patient's clinical signs and symptoms are similar to those described previously in 11 Japanese patients. However, unlike those patients, our patient demonstrates symptomatic response to topical treatment, no seasonal association to her condition, and to date, incomplete resolution of her disease after more than 2 years. This case highlights that Landolt ring-shaped epithelial keratopathy, a novel corneal disease of unclear origin, has relevance outside of the Japanese population.

The excitability of ipsilateral motor evoked potentials is not task-specific and spatially distinct from the contralateral motor hotspot.

OBJECTIVE: The role of ipsilateral descending motor pathways in voluntary movement of humans is still a matter of debate, with partly contradictory results. The aim of our study therefore was to examine the excitability of ipsilateral motor evoked potentials (iMEPs) regarding site and the specificity for unilateral and bilateral elbow flexion extension tasks. METHODS: MR-navigated transcranial magnetic stimulation mapping of the dominant hemisphere was performed in twenty healthy participants during tonic unilateral (iBB), bilateral homologous (bBB) or bilateral antagonistic elbow flexion-extension (iBB-cAE), the map center of gravity (CoG) and iMEP area from BB were obtained. RESULTS: The map CoG of the ipsilateral BB was located more anterior-laterally than the hotspot of the contralateral BB within the primary motor cortex, with a significant difference in CoG in iBB and iBB-cAE, but not bBB compared to the hotspot for the contralateral BB (each p < 0.05). However, different tasks had no effect on the size of the iMEPs. CONCLUSION: Our data demonstrated that excitability of ipsilateral and contralateral MEP differ spatially in a task-specific manner suggesting the involvement of different motor networks within the motor cortex.

Corticomotor pathway function and recovery after stroke: a look back and a way forward.

Stroke is a leading cause of adult disability that results in motor deficits and reduced independence. Regaining independence relies on motor recovery, particularly regaining function of the hand and arm. This review presents evidence from human studies that have used transcranial magnetic stimulation (TMS) to identify neurophysiological mechanisms underlying upper limb motor recovery early after stroke. TMS studies undertaken at the subacute stage after stroke have identified several neurophysiological factors that can drive motor impairment, including membrane excitability, the recruitment of corticomotor neurons, and glutamatergic and GABAergic neurotransmission. However, the inherent variability and subsequent poor reliability of measures derived from motor evoked potentials (MEPs) limit the use of TMS for prognosis at the individual patient level. Currently, prediction tools that provide the most accurate information about upper limb motor outcomes for individual patients early after stroke combine clinical measures with a simple neurophysiological biomarker based on MEP presence or absence, i.e. MEP status. Here, we propose a new compositional framework to examine MEPs across several upper limb muscles within a threshold matrix. The matrix can provide a more comprehensive view of corticomotor function and recovery after stroke by quantifying the evolution of subthreshold and suprathreshold MEPs through compositional analyses. Our contention is that subthreshold responses might be the most sensitive to reduced output of corticomotor neurons, desynchronized firing of the remaining neurons, and myelination processes that occur early after stroke. Quantifying subthreshold responses might provide new insights into post-stroke neurophysiology and improve the accuracy of prediction of upper limb motor outcomes.

Effective refractive error coverage and spectacle coverage among school children in Telangana, South India.

BACKGROUND: Uncorrected refractive error (URE) is one of the leading causes of childhood vision impairment. Increasing effective refractive error coverage (e-REC) is one of the main indicators of WHO's 2030 global eye health targets. The aim of this study is to estimate the e-REC and spectacle coverage among school children in Telangana, South India. METHODS: School children aged 4-15 years in the study locations underwent vision screening using 6/12 tumbling E optotype by trained community eye health workers in the schools. Those failing the initial vision screening and/or found to be having eye conditions were referred to a nearby referral centre appropriately, where they underwent detailed eye examination. RESULTS: A total of 774,184 children were screened in schools of which 51.49% were boys. The mean age was 9.40 ± 3.27 years. The prevalence of URE was 1.44% (95%CI:1.41-1.46) of which myopia was 1.38% (95%CI: 1.35-1.41). In multivariate analysis, the risk of myopia was higher among older children (Adj.OR: 17.04; 95%CI: 14.64-19.85), those residing in urban areas (Adj.OR:3.05, 95%CI:2.60-3.57), those with disabilities (Adj.OR:2.61, 95%CI:2.00-3.39) and among girls (Adj.OR:1.30, 95%CI:1.25-1.35) (P < 0.001). The overall e-REC was 56.97% and the spectacle coverage was 62.83%. CONCLUSION: The need for interventions to improve e-REC to achieve 2030 global eye health target is eminent among children in this region. Improving refractive services through school eye health programs could aid in accelerating this process to achieve the target. Myopia being the most common type of RE, the risk factors included increasing age, urban location, and presence of disability.

Podcast on Cross-speciality Perspectives on Practical Management of Atopic Dermatitis-Associated Ocular Surface Diseases.

There is a growing awareness among dermatology providers of ocular comorbidities in patients with the chronic inflammatory skin disease atopic dermatitis (AD). For example, the prevalence of ocular surface diseases (OSD) such as conjunctivitis is higher in patients with AD than in the general population, and the use of some AD treatments may be associated with OSD. In a recent review published in the Journal of the American Academy of Dermatology, dermatologists and ophthalmologists provided an overview of the different types, etiology, pathophysiology, and practical management of OSD associated with AD. This review included a suggested treatment algorithm that champions a partnership between dermatology providers and eye care providers for optimal screening, diagnosis, and care. In this podcast article, a dermatologist and ophthalmologist who were authors on this review are joined by a nurse practitioner moderator to discuss how these concepts can be adapted to clinical practice, inclusive of dermatologists, eye care providers, and relevant advanced practice providers. This podcast focuses on the authors' clinical experiences and highlights the key aspects of optimal care, including exploring additional questions to answer with future research.

Applications of Repetitive Transcranial Magnetic Stimulation to Improve Upper Limb Motor Performance After Stroke: A Systematic Review.

BACKGROUND: Noninvasive brain stimulation (NIBS) is a promising technique for improving upper limb motor performance post-stroke. Its application has been guided by the interhemispheric competition model and typically involves suppression of contralesional motor cortex. However, the bimodal balance recovery model prompts a more tailored application of NIBS based on ipsilesional corticomotor function. OBJECTIVE: To review and assess the application of repetitive transcranial magnetic stimulation (rTMS) protocols that aimed to improve upper limb motor performance after stroke. METHODS: A PubMed search was conducted for studies published between 1st January 2005 and 1st November 2022 using rTMS to improve upper limb motor performance of human adults after stroke. Studies were grouped according to whether facilitatory or suppressive rTMS was applied to the contralesional hemisphere. RESULTS: Of the 492 studies identified, 70 were included in this review. Only 2 studies did not conform to the interhemispheric competition model, and facilitated the contralesional hemisphere. Only 21 out of 70 (30%) studies reported motor evoked potential (MEP) status as a biomarker of ipsilesional corticomotor function. Around half of the studies (37/70, 53%) checked whether rTMS had the expected effect by measuring corticomotor excitability (CME) after application. CONCLUSION: The interhemispheric competition model dominates the application of rTMS post-stroke. The majority of recent and current studies do not consider bimodal balance recovery model for the application of rTMS. Evaluating CME after the application rTMS could confirm that the intervention had the intended neurophysiological effect. Future studies could select patients and apply rTMS protocols based on ipsilesional MEP status.

Mediators of Visual Acuity in Descemet Membrane Endothelial Keratoplasty and Ultrathin Descemet Stripping Automated Endothelial Keratoplasty.

PURPOSE: The aim of this study was to investigate mediators of visual acuity in ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) compared with Descemet membrane endothelial keratoplasty (DMEK). METHODS: This was a prespecified secondary analysis of the Descemet Endothelial Thickness Comparison Trial, a prospective, randomized controlled trial comparing UT-DSAEK with DMEK. Subjects with Fuchs endothelial dystrophy or pseudophakic bullous keratopathy presenting to 2 academic centers were enrolled and randomized to either UT-DSAEK (n = 25 eyes) or DMEK (n = 25 eyes). Higher order aberrations (HOAs) and corneal densitometry were measured with Pentacam Scheimpflug imaging at 3, 6, 12, and 24 months. RESULTS: The posterior corneal surface at the 6.0-mm optical zone had significantly less total HOAs (P <0.001) in the DMEK group compared with UT-DSAEK at 24 months. Anterior and posterior corneal densitometry improved from baseline to 24 months for both UT-DSAEK and DMEK, but there was no significant difference between the 2 groups. Corneal densitometry and posterior HOAs were both associated with best-corrected visual acuity (P <0.05). DMEK had 1.3 logarithm of the minimum angle of resolution better visual acuity compared with UT-DSAEK at 24 months. Approximately 64% of this effect was mediated through posterior HOAs, whereas none was mediated through anterior HOAs or densitometry. CONCLUSIONS: Decreased posterior HOAs mediate better visual acuity and account for improved vision after DMEK compared with UT-DSAEK. Corneal light scatter as measured by densitometry is similar between UT-DSAEK and DMEK, indicating that the increased thickness and stromal-stromal interface in UT-DSAEK do not significantly affect visual acuity.

Reliability of a TMS-derived threshold matrix of corticomotor function.

Transcranial magnetic stimulation (TMS) studies typically focus on suprathreshold motor evoked potentials (MEPs), overlooking small MEPs representing subthreshold corticomotor pathway activation. Assessing subthreshold excitability could provide insights into corticomotor pathway integrity and function, particularly in neurological conditions like stroke. The aim of the study was to examine the test-retest reliability of metrics derived from a novel compositional analysis of MEP data from older adults. The study also compared the composition between the dominant (D) and non-dominant (ND) sides and explored the association between subthreshold responses and resting motor threshold. In this proof-of-concept study, 23 healthy older adults participated in two identical experimental sessions. Stimulus-response (S-R) curves and threshold matrices were constructed using single-pulse TMS across intensities to obtain MEPs in four upper limb muscles. S-R curves had reliable slopes for every muscle (Intraclass Correlation Coefficient range = 0.58-0.88). Subliminal and suprathreshold elements of the threshold matrix showed good-excellent reliability (D subliminal ICC = 0.83; ND subliminal ICC = 0.79; D suprathreshold ICC = 0.92; ND suprathreshold ICC = 0.94). By contrast, subthreshold elements of the matrix showed poor reliability, presumably due to a floor effect (D subthreshold ICC = 0.39; ND subthreshold ICC = 0.05). No composition differences were found between D and ND sides (suprathreshold BF01 = 3.85; subthreshold BF01 = 1.68; subliminal BF01 = 3.49). The threshold matrix reliably assesses subliminal and suprathreshold MEPs in older adults. Further studies are warranted to evaluate the utility of compositional analyses for assessing recovery of corticomotor pathway function after neurological injury.

Variations in the prevalence of vision impairment across regions among school children in Telangana State, South India.

Purpose: Undetected vision impairment (VI) could negatively affect the overall development in children. School vision screening program is a viable and cost-effective approach for the early identification and management of VI. Aim: This study aims to estimate the prevalence of VI, its risk factors, and ocular morbidity among school children in Telangana, South India. Methods: Children aged 4-15 years attending schools in the study area were screened in this study. The vision screenings were performed in schools by trained community eye health workers using 6/12 tumbling E optotypes. Children who failed the test and/or presented with other eye conditions were referred to vision centers or secondary and tertiary eye care centers. A comprehensive eye examination was conducted in these centers, including cycloplegic refraction and fundus examination. Results: A total of 774,184 children, with a mean age of 9.4 ± 3.27 years, were screened. Overall, 51.49% (N = 398,596) were male. In total, 4.33% [N = 33,528; 95% confidence interval (CI): 4.29-4.38] required referral services, while 1.16% (N = 9,002) had a presenting visual acuity of < 6/12. Multivariate analysis showed a high risk of VI among older children [Adj. odds ratio (OR): 5.75; 95% CI: 5.18-6.38], those with disabilities (Adj. OR: 5.12; 95% CI: 4.14-6.33), female gender (Adj. OR: 1.29; 95% CI: 1.24 - 1.35), and those residing in the urban areas (Adj. OR: 2.87; 95% CI: 2.42-3.39). The main cause of VI was uncorrected refractive errors (74.14%). Conclusion: The prevalence of VI among school children was 1.16% in Telangana, South India, and refractive error was the leading cause of VI among this population. Increasing age, urban location, female gender and other disabilities increase the risk of VI among children.

Modulation of ipsilateral motor evoked potentials during bimanual coordination tasks.

Introduction: Ipsilateral motor evoked potentials (iMEPs) are difficult to obtain in distal upper limb muscles of healthy participants but give a direct insight into the role of ipsilateral motor control. Methods: We tested a new high-intensity double pulse transcranial magnetic stimulation (TMS) protocol to elicit iMEPs in wrist extensor and flexor muscles during four different bimanual movements (cooperative-asymmetric, cooperative-symmetric, non-cooperative-asymmetric and non-cooperative-symmetric) in 16 participants. Results: Nine participants showed an iMEP in the wrist extensor in at least 20% of the trials in each of the conditions and were classified as iMEP+ participants. iMEP persistence was greater for cooperative (50.5 ± 28.8%) compared to non-cooperative (31.6 ± 22.1%) tasks but did not differ between asymmetric and symmetric tasks. Area and amplitude of iMEPs were also increased during cooperative (area = 5.41 ± 3.4 mV × ms; amplitude = 1.60 ± 1.09 mV) compared to non-cooperative (area = 3.89 ± 2.0 mV × ms; amplitude = 1.12 ± 0.56 mV) tasks and unaffected by task-symmetry. Discussion: The upregulation of iMEPs during common-goal cooperative tasks shows a functional relevance of ipsilateral motor control in bimanual movements. The paired-pulse TMS protocol is a reliable method to elicit iMEPs in healthy participants and can give new information about neural control of upper limb movements. With this work we contribute to the research field in two main aspects. First, we describe a reliable method to elicit ipsilateral motor evoked potentials in healthy participants which will be useful in further advancing research in the area of upper limb movements. Second, we add new insight into the motor control of bimanual movements. We were able to show an upregulation of bilateral control represented by increased ipsilateral motor evoked potentials in cooperative, object-oriented movements compared to separate bimanual tasks. This result might also have an impact on neurorehabilitation after stroke.

Muscle synergies are associated with intermuscular coherence and cortico-synergy coherence in an isometric upper limb task.

To elucidate the underlying physiological mechanisms of muscle synergies, we investigated long-range functional connectivity by cortico-muscular (CMC), intermuscular (IMC) and cortico-synergy (CSC) coherence. Fourteen healthy participants executed an isometric upper limb task in synergy-tuned directions. Cortical activity was recorded using 32-channel electroencephalography (EEG) and muscle activity using 16-channel electromyography (EMG). Using non-negative matrix factorisation (NMF), we calculated muscle synergies from two different tasks. A preliminary multidirectional task was used to identify synergy-preferred directions (PDs). A subsequent coherence task, consisting of generating forces isometrically in the synergy PDs, was used to assess the functional connectivity properties of synergies. Overall, we were able to identify four different synergies from the multidirectional task. A significant alpha band IMC was consistently present in all extracted synergies. Moreover, IMC alpha band was higher between muscles with higher weights within a synergy. Interestingly, CSC alpha band was also significantly higher across muscles with higher weights within a synergy. In contrast, no significant CMC was found between the motor cortex area and synergy muscles. The presence of a shared input onto synergistic muscles within a synergy supports the idea of neurally derived muscle synergies that build human movement. Our findings suggest cortical modulation of some of the synergies and the consequential existence of shared input between muscles within cortically modulated synergies.

A global pause generates nonselective response inhibition during selective stopping.

Selective response inhibition may be required when stopping a part of a multicomponent action. A persistent response delay (stopping-interference effect) indicates nonselective response inhibition during selective stopping. This study aimed to elucidate whether nonselective response inhibition is the consequence of a global pause process during attentional capture or specific to a nonselective cancel process during selective stopping. Twenty healthy human participants performed a bimanual anticipatory response inhibition paradigm with selective stop and ignore signals. Frontocentral and sensorimotor beta-bursts were recorded with electroencephalography. Corticomotor excitability and short-interval intracortical inhibition in primary motor cortex were recorded with transcranial magnetic stimulation. Behaviorally, responses in the non-signaled hand were delayed during selective ignore and stop trials. The response delay was largest during selective stop trials and indicated that stopping-interference could not be attributed entirely to attentional capture. A stimulus-nonselective increase in frontocentral beta-bursts occurred during stop and ignore trials. Sensorimotor response inhibition was reflected in maintenance of beta-bursts and short-interval intracortical inhibition relative to disinhibition observed during go trials. Response inhibition signatures were not associated with the magnitude of stopping-interference. Therefore, nonselective response inhibition during selective stopping results primarily from a nonselective pause process but does not entirely account for the stopping-interference effect.

Association of Brain Age, Lesion Volume, and Functional Outcome in Patients With Stroke.

BACKGROUND AND OBJECTIVES: Functional outcomes after stroke are strongly related to focal injury measures. However, the role of global brain health is less clear. In this study, we examined the impact of brain age, a measure of neurobiological aging derived from whole-brain structural neuroimaging, on poststroke outcomes, with a focus on sensorimotor performance. We hypothesized that more lesion damage would result in older brain age, which would in turn be associated with poorer outcomes. Related, we expected that brain age would mediate the relationship between lesion damage and outcomes. Finally, we hypothesized that structural brain resilience, which we define in the context of stroke as younger brain age given matched lesion damage, would differentiate people with good vs poor outcomes. METHODS: We conducted a cross-sectional observational study using a multisite dataset of 3-dimensional brain structural MRIs and clinical measures from the ENIGMA Stroke Recovery. Brain age was calculated from 77 neuroanatomical features using a ridge regression model trained and validated on 4,314 healthy controls. We performed a 3-step mediation analysis with robust mixed-effects linear regression models to examine relationships between brain age, lesion damage, and stroke outcomes. We used propensity score matching and logistic regression to examine whether brain resilience predicts good vs poor outcomes in patients with matched lesion damage. RESULTS: We examined 963 patients across 38 cohorts. Greater lesion damage was associated with older brain age (ß = 0.21; 95% CI 0.04-0.38, p = 0.015), which in turn was associated with poorer outcomes, both in the sensorimotor domain (ß = -0.28; 95% CI -0.41 to -0.15, p < 0.001) and across multiple domains of function (ß = -0.14; 95% CI -0.22 to -0.06, p < 0.001). Brain age mediated 15% of the impact of lesion damage on sensorimotor performance (95% CI 3%-58%, p = 0.01). Greater brain resilience explained why people have better outcomes, given matched lesion damage (odds ratio 1.04, 95% CI 1.01-1.08, p = 0.004). DISCUSSION: We provide evidence that younger brain age is associated with superior poststroke outcomes and modifies the impact of focal damage. The inclusion of imaging-based assessments of brain age and brain resilience may improve the prediction of poststroke outcomes compared with focal injury measures alone, opening new possibilities for potential therapeutic targets.

Comparing anticipatory and stop-signal response inhibition with a novel, open-source selective stopping toolbox.

Response inhibition is essential for terminating inappropriate actions and, in some cases, may be required selectively. Selective stopping can be investigated with multicomponent anticipatory or stop-signal response inhibition paradigms. Here we provide a freely available open-source Selective Stopping Toolbox (SeleST) to investigate selective stopping using either anticipatory or stop-signal task variants. This study aimed to evaluate selective stopping between the anticipatory and stop-signal variants using SeleST and provide guidance to researchers for future use. Forty healthy human participants performed bimanual anticipatory response inhibition and stop-signal tasks in SeleST. Responses were more variable and slowed to a greater extent during the stop-signal than in the anticipatory paradigm. However, the stop-signal paradigm better conformed to the assumption of the independent race model of response inhibition. The expected response delay during selective stop trials was present in both variants. These findings indicate that selective stopping can successfully be investigated with either anticipatory or stop-signal paradigms in SeleST. We propose that the anticipatory paradigm should be used when strict control of response times is desired, while the stop-signal paradigm should be used when it is desired to estimate stop-signal reaction time with the independent race model. Importantly, the dual functionality of SeleST allows researchers flexibility in paradigm selection when investigating selective stopping.

Proactive Interhemispheric Disinhibition Supports Response Preparation during Selective Stopping.

Response inhibition is essential for terminating inappropriate actions. A substantial response delay may occur in the nonstopped effector when only part of a multieffector action is terminated. This stopping-interference effect has been attributed to nonselective response inhibition processes and can be reduced with proactive cuing. This study aimed to elucidate the role of interhemispheric primary motor cortex (M1-M1) influences during selective stopping with proactive cuing. We hypothesized that stopping-interference would be reduced as stopping certainty increased because of proactive recruitment of interhemispheric facilitation or inhibition when cued to respond or stop, respectively. Twenty-three healthy human participants of either sex performed a bimanual anticipatory response inhibition paradigm with cues signaling the likelihood of a stop-signal occurring. Dual-coil transcranial magnetic stimulation was used to determine corticomotor excitability (CME), interhemispheric inhibition (IHI), and interhemispheric facilitation (IHF) in the left hand at rest and during response preparation. Response times slowed and stopping-interference decreased with increased stopping certainty. Proactive response inhibition was marked by a reduced rate of rise and faster cancel time in electromyographical bursts during stopping. There was a nonselective release of IHI but not CME from rest to in-task response preparation, whereas IHF was not observed in either context. An effector-specific reduction in CME but no reinstatement of IHI was observed when the left hand was cued to stop. These findings indicate that stopping speed and selectivity are better with proactive cueing and that interhemispheric M1-M1 channels modulate inhibitory tone during response preparation to support going but not proactive response inhibition.SIGNIFICANCE STATEMENT Response inhibition is essential for terminating inappropriate actions and, in some cases, may be required for only part of a multieffector action. The present study examined interhemispheric influences between the primary motor cortices during selective stopping with proactive cuing. Stopping selectivity was greater with increased stopping certainty and was marked by proactive adjustments to the hand cued to stop and hand cued to respond separately. Inhibitory interhemispheric influences were released during response preparation but were not directly involved in proactive response inhibition. These findings indicate that between-hand stopping can be selective with proactive cuing, but cue-related improvements are unlikely to reflect the advance engagement of interhemispheric influences between primary motor cortices.

Cyclodialysis Cleft After Secondary Intraocular Lens Placement With Yamane Technique.

PURPOSE: The purpose of this study was to report a rare case of cyclodialysis cleft after secondary intraocular lens (IOL) placement using the Yamane flanged intrascleral haptic fixation technique. METHODS: This study is an observational case report. RESULTS: A 74-year-old man with an ocular history of spontaneously dislocated IOL and subsequent anterior chamber IOL (ACIOL) placement presented with monocular diplopia secondary to ACIOL subluxation. The patient underwent explantation of the subluxed ACIOL and placement of a scleral-fixated IOL using the Yamane technique. The postoperative course was complicated by persistent hypotony, prompting ultrasound biomicroscopy, which revealed a cyclodialysis cleft adjacent to one of the externalized IOL haptics. The haptic was discovered in the involved supraciliary space while performing direct cyclopexy. The cyclodialysis cleft closed with return to physiologic intraocular pressure. CONCLUSIONS: Cyclodialysis cleft formation is a possible complication of scleral IOL fixation and should be suspected in cases of prolonged postoperative hypotony. Extended longitudinal tracking of the needle and haptic through the supraciliary space may be one mechanism for cyclodialysis cleft formation in the Yamane technique.

Arguments for the biological and predictive relevance of the proportional recovery rule.

The proportional recovery rule (PRR) posits that most stroke survivors can expect to reduce a fixed proportion of their motor impairment. As a statistical model, the PRR explicitly relates change scores to baseline values - an approach that arises in many scientific domains but has the potential to introduce artifacts and flawed conclusions. We describe approaches that can assess associations between baseline and changes from baseline while avoiding artifacts due either to mathematical coupling or to regression to the mean. We also describe methods that can compare different biological models of recovery. Across several real datasets in stroke recovery, we find evidence for non-artifactual associations between baseline and change, and support for the PRR compared to alternative models. We also introduce a statistical perspective that can be used to assess future models. We conclude that the PRR remains a biologically relevant model of stroke recovery.

Intracortical facilitation and inhibition in human primary motor cortex during motor skill acquisition.

The primary motor cortex (M1) is critical for movement execution, but its role in motor skill acquisition remains elusive. Here, we examine the role of M1 intracortical circuits during skill acquisition. Paired-pulse transcranial magnetic stimulation (TMS) paradigms of short-interval intracortical facilitation (SICF) and inhibition (SICI) were used to assess excitatory and inhibitory circuits, respectively. We hypothesised that intracortical facilitation and inhibition circuits in M1 would be modulated to support acquisition of a novel visuomotor skill. Twenty-two young, neurologically healthy adults trained with their nondominant hand on a skilled and non-skilled sequential visuomotor isometric finger abduction task. Electromyographic recordings were obtained from the nondominant first dorsal interosseous (FDI) muscle. Corticomotor excitability, SICF, and SICI were examined before, at the midway point, and after the 10-block motor training. SICI was assessed using adaptive threshold-hunting procedures. Task performance improved after the skilled, but not non-skilled, task training, which likely reflected the increase in movement speed during training. The amplitudes of late SICF peaks were modulated with skilled task training. There was no modulation of the early SICF peak, SICI, and corticomotor excitability with either task training. There was also no association between skill acquisition and SICF or SICI. The findings indicate that excitatory circuitries responsible for the generation of late SICF peaks, but not the early SICF peak, are modulated in motor skill acquisition for a sequential visuomotor isometric finger abduction task.

Descemet membrane endothelial keratoplasty in complex eyes.

PURPOSE OF REVIEW: To review the current literature on Descemet membrane endothelial keratoplasty (DMEK) in complex eyes. RECENT FINDINGS: DMEK surgery has become a standardized procedure in Fuchs endothelial dystrophy and simple bullous keratopathy. But eyes with more complex disease present unique intraoperative and postoperative challenges to the DMEK surgeon. Poor visualization during surgery, complex anterior segment anatomy, altered anterior chamber dynamics, glaucoma shunts, and congenital or iatrogenic missing or altered iris and lens make DMEK surgery extremely difficult to accomplish. SUMMARY: DMEK is feasible in complex eyes, including advanced bullous keratopathy, eyes with history of glaucoma or vitreoretinal surgery, previous penetrating keratoplasty, uveitis, pediatric, and congenital anterior segment disorders. The tools and methods reported in the literature to accomplish DMEK in complex eyes vary widely with no particular consensus or standardization of techniques. The outcomes noted for some of these conditions demonstrate the difficulty of the surgery and the uncertainty of long-term graft survival in complex eyes. Both surgical standardization and randomized prospective data will better help elucidate DMEK's role in the corneal rehabilitation of complex eyes.

Visual impairment and refractive errors in school children in Andhra Pradesh, India.

Purpose: Addressing childhood vision impairment (VI) is one of the main goals of the World Health Organization's (WHO) combating blindness strategies. The primary aim of this study was to estimate the prevalence of VI, causes, and its risk factors in school children in Krishna district, Andhra Pradesh, India. Methods: Children aged 4-15 years were screened in schools using the 6/12 Snellen optotype by trained community eye health workers, and those who failed the test and those reported or found to have obvious eye conditions were referred to primary (VC), secondary (SC), or tertiary (TC) care centre appropriately, where they underwent a complete eye examination including cycloplegic refraction and fundus examination. Results: A total of 56,988 children were screened, of whom 51.18% were boys. The mean age was 9.69 ± 3.26 years (4-15 years). Overall, 2,802/56,988 (4.92%) children were referred to a VC, of which 632/56,988 (1.11%) required referral to SC/TC. PVA of <6/12 was found in 1.72% (95% confidence interval [CI]: 1.61-1.83). The prevalence of refractive error (corrected and uncorrected) was 2.38% (95% CI: 2.26-2.51) and myopia was 2.17% (95% CI: 2.05-2.29). In multivariable analysis, older children, those in urban schools, private schools, and children with a disability had an increased risk of VI and myopia. Additionally, the risk of myopia was higher among girls than boys. Of those referred and reached SC/TC, 73.64% were due to avoidable causes. Conclusion: Childhood VI prevalence was 1.72% in this region. Uncorrected refractive error (URE) was the major cause of VI in children. Older age, schools in urban locations, private schools, and the presence of disability were associated with the risk of VI among children.