Causes of Childhood Blindness in the United States Using the IRIS® Registry (Intelligent Research in Sight).

PURPOSE: To investigate causes of childhood blindness in the United States using the IRIS® Registry (Intelligent Research in Sight). DESIGN: Cross-sectional study. PARTICIPANTS: Patients ≤ 18 years of age with visual acuity (VA) 20/200 or worse in their better-seeing eye in the IRIS Registry during 2018. METHODS: Causes of blindness were classified by anatomic site and specific diagnoses. MAIN OUTCOME MEASURES: Percentages of causes of blindness. RESULTS: Of 81 164 children with 2018 VA data in the IRIS Registry, 961 (1.18%) had VA 20/200 or worse in their better-seeing eye. Leading causes of blindness were retinopathy of prematurity (ROP) in 301 patients (31.3%), nystagmus in 78 patients (8.1%), and cataract in 64 patients (6.7%). The retina was the leading anatomic site (47.7%) followed by optic nerve (11.6%) and lens (10.0%). A total of 52.4% of patients had treatable causes of blindness. CONCLUSIONS: This analysis offers a unique cross-sectional view of childhood blindness in the United States using a clinical data registry. More than one-half of blind patients had a treatable cause of blindness. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Ocular Motor Nerve Palsy After Traumatic Brain Injury: A Claims Database Study.

BACKGROUND: Traumatic brain injury (TBI) is one of the common causes of ocular motor nerve (oculomotor nerve [CN3], trochlear nerve [CN4], and abducens nerve [CN6]) palsies, but there has been no large study of ocular motor nerve palsy caused by TBI. This study aimed to investigate the characteristics of and differences in ocular motor nerve palsy after TBI, according to patient age and severity of TBI. METHODS: This was a population-based retrospective cohort study that included patients who had ocular motor nerve palsy after TBI with ≥6 months of continuous enrollment using claims data from the IBM MarketScan Research Databases (2007-2016). We assessed sex, age at the first diagnosis of TBI, the severity of TBI, and the rates of strabismus procedures according to the age and severity of TBI. The rates of muscle transposition surgery and chemodenervation in CN3, CN4, and CN6 palsy were investigated. RESULTS: A total of 2,606,600 patients with TBI met the inclusion criteria. Among them, 1,851 patients (0.071%) had ocular motor nerve palsy after TBI. The median age of the patients was 39 (Q1-Q3: 19-54) years, and 42.4% of the patients were female. The median continuous enrollment period after the first diagnosis of TBI was 22 (Q1-Q3: 12-38) months. Of the 1,350,843 children with TBI, 454 (0.026%) had ocular motor nerve palsy. Of the 1,255,757 adults with TBI, 1,397 (0.111%) had ocular motor nerve palsy. Among these 1,851 patients, CN4 palsy (697, 37.7%) occurred most frequently, and strabismus procedures were performed in 237 patients (12.8%). CN6 palsy developed most frequently in children. More children (16.5%) underwent strabismus surgeries than adults (11.6%) ( P = 0.006). The proportion of CN4 palsy (52.3%) was higher while the proportion of CN3 palsy (15.5%) was lower in patients with mild TBI than in patients with moderate-to-severe TBI ( P < 0.001). CONCLUSIONS: CN4 palsy developed most frequently among patients of all ages, and only approximately 13% of the patients underwent strabismus procedures for ocular motor nerve palsy after TBI. The rate of development of ocular motor nerve palsy was approximately 4.3 times lower in children than adults, and children most frequently had CN6 palsy after TBI.

Risk Factors for Retinal Detachment Repair After Pediatric Cataract Surgery in the United States.

Purpose: To determine the cumulative incidence of retinal detachment (RD) repair following pediatric cataract surgery and identify the associated risk factors. Design: US population-based insurance claims retrospective cohort study. Participants: Patients ≤ 18 years old who underwent cataract surgery in 2 large databases: Optum Clinformatics (2003-2021) and IBM MarketScan (2007-2016). Methods: Individuals with ≥ 6 months of prior enrollment were included, and those with a history of RD, RD repair, traumatic cataract, spherophakia, or ectopia lentis were excluded. The primary outcome was time between initial cataract surgery and RD repair. The risk factors investigated included age, sex, persistent fetal vasculature (PFV), prematurity, intraocular lens (IOL) placement, and pars plana lensectomy approach. Main Outcome Measures: Kaplan-Meier estimated cumulative incidence of RD repair 5 years after cataract surgery and hazard ratios (HRs) with 95% confidence intervals (CIs) from multivariable Cox proportional hazards regression models. Results: Retinal detachment repair was performed on 47 of 3289 children included in this study. The cumulative incidence of RD repair within 5 years of cataract surgery was 2.0% (95% CI, 1.3%-2.6%). Children requiring RD repair were more likely to have a history of prematurity or PFV and less likely to have an IOL placed (all P < 0.001). Factors associated with RD repair in the multivariable analysis included a history of prematurity (HR, 6.89; 95% CI, 3.26-14.56; P < 0.001), PFV diagnosis (HR, 8.20; 95% CI, 4.11-16.37; P < 0.001), and IOL placement (HR, 0.44; 95% CI, 0.21-0.91; P = 0.03). Age at surgery, sex, and pars plana lensectomy approach were not significantly associated with RD repair after adjusting for all other covariates. Conclusions: Approximately 2% of patients will undergo RD repair within 5 years of pediatric cataract surgery. Children with a history of PFV and prematurity undergoing cataract surgery without IOL placement are at the greatest risk.

Comparison of the Structure-Function Relationship Between Advanced Primary Open Angle Glaucoma and Normal Tension Glaucoma.

PURPOSE: The aim was to investigate and compare the characteristics of visual field (VF) defects in primary open angle glaucoma (POAG) and normal-tension glaucoma (NTG) with advanced glaucomatous damage and to determine whether the structure-function relationships found in advanced glaucoma differ based on their glaucoma classification. PATIENTS AND METHODS: Ninety-seven eyes of 97 patients (59 eyes with POAG and 38 eyes with NTG) with advanced glaucoma were included in this cross-sectional study. Scores at each test point of the 30-2 VF total deviation map were recorded, and average values at each test point were point-wise compared between the groups. Peripapillary retinal nerve fiber layer (RNFL) and macular thickness (total, RNFL, ganglion cell layer, and inner plexiform layer thickness) were measured. The structure-function relationship based on the map of Garway-Heath was determined and compared between the 2 groups. RESULTS: At advanced stage of glaucoma, POAG eyes demonstrated more diffusely distributed VF defects, whereas NTG eyes had more severe VF defects at the superior nasal quadrant, showing increased asymmetry. Overall, peripapillary RNFL, macular ganglion cell layer, and macular inner plexiform layer thickness showed good relationships with 30-2 VF parameters in both groups. However, in total macula and macular RNFL thickness, the structure-function relationships tended to show different characteristics depending on the glaucoma classification; NTG eyes showed overall better relationships. CONCLUSIONS: In advanced glaucoma, differences in patterns of VF damage were found between POAG and NTG eyes. Conventional peripapillary RNFL and macular measurements showed generally good performance for estimating functional status, particularly in NTG eyes.

Incidence of infectious complications following strabismus surgery.

A total of 167 cases (0.111%) of infectious complications (endophthalmitis, orbital cellulitis, preseptal cellulitis, and postoperative infection) were identified in patients after strabismus surgery. The incidence of postoperative endophthalmitis was approximately 1 per 13,700 strabismus surgeries (0.007%) among 151,011 strabismus surgeries in US claims databases.

Types of Surgery Performed and Reoperation Rate for Congenital Superior Oblique Palsy: a Claims Database Study.

PURPOSE: To investigate types of surgeries performed to treat a presumed congenital superior oblique palsy (SOP) and the reoperation rate. METHODS: This was a population-based retrospective cohort study using claims data from the United States. Patients who underwent strabismus surgery for a presumed congenital SOP with ≥ 3 months of continuous enrolment after the initial surgery were included. We investigated age, surgical methods and the time interval between the initial surgery and reoperation. The hazard ratios for reoperation were estimated according to the surgical methods using Cox regression analysis. RESULTS: A total of 3,998 patients underwent surgery for presumed congenital SOP; 2,981 (74.6%) on only one vertical muscle (excluding superior oblique). Reoperation was performed on 427 patients (10.7%). Compared to patients who underwent unilateral surgery on one vertical muscle (excluding superior oblique muscle), patients who underwent surgery that included the superior oblique muscle (unilateral 2.08; 95% CI, 1.61-2.67, p < 0.001; bilateral 2.44; 95% CI, 1.40-4.28, p = 0.002) and two or more vertical muscles (excluding the superior oblique muscle) (unilateral 2.99; 95% CI, 2.00-4.49, p < 0.001; bilateral 1.68; 95% CI, 1.23-2.28, p = 0.001) had increased hazard ratios for reoperation. The median period between the initial surgery and reoperation was 168.0 [Q1-Q3 84.0-407.8] days and negatively correlated with patient age at initial surgery (r = -0.199, p < 0.001). CONCLUSION: The reoperation rate for presumed congenital SOP was 10.7%. Patients who underwent surgery on two or more vertical muscles or the superior oblique muscle had an increased risk of reoperation.

Risk Factors for Reoperation after Strabismus Surgery among Patients with Thyroid Eye Disease.

PURPOSE: To examine risk factors for strabismus surgery reoperation in patients with thyroid eye disease (TED). DESIGN: Retrospective cohort study. METHODS: An insurance claims database was used to identify patients with TED who underwent at least one strabismus operation between 2003 and 2019. We recorded specific muscles operated on, as well as the timing and frequency of reoperations. Cox regressions were used to estimate associations between time to reoperation and patient and primary surgery characteristics. RESULTS: Of the 448 patients who met inclusion criteria, 111 (24.8%) underwent a reoperation. Patients were followed for an average of 5.4 ± 3.0 years after their initial strabismus surgery. The rates of reoperation among patients whose initial surgery involved horizontal muscles only, vertical muscles only, and horizontal and vertical muscles were 29 of 120 (24.2%), 33 of 169 (19.5%), and 49 of 159 (30.8%) respectively (P = .05). The number of muscles operated on initially was the only independent predictor for undergoing a strabismus surgery reoperation (odds ratio, 1.27; 95% confidence interval, 1.03-1.57; P = .03). The number of muscles operated on initially was also associated with shorter time to first reoperation (hazard ratio, 1.22; 95% confidence interval, 1.02-1.46; P = .03). Age at first surgery, time between diagnosis of TED and first strabismus surgery, gender, race, and use of adjustable sutures were not associated with time to reoperation. CONCLUSIONS: Approximately 1 in 4 patients with TED require reoperation after strabismus surgery. The number of muscles operated on was the only independent predictor for both undergoing a reoperation and time to first reoperation.

Effects of prolonged use of virtual reality smartphone-based head-mounted display on visual parameters: a randomised controlled trial.

We investigated the effects of using a virtual reality smartphone-based head-mounted display (VR SHMD) device for 2 h on visual parameters. Fifty-eight healthy volunteers were recruited. The participants played games using VR SHMD or smartphones for 2 h on different days. Visual parameters including refraction, accommodation, convergence, stereopsis, and ocular alignment and measured choroidal thickness before and after the use of VR SHMD or smartphones were investigated. Subjective symptoms were assessed using questionnaires. We analyzed the differences in visual parameters before and after the use of VR SHMD or smartphones and correlations between baseline visual parameters and those after the use of the devices. Significant changes were observed in near-point convergence and accommodation, exophoric deviation, stereopsis, and accommodative lag after the use of VR SHMD but not after that of smartphones. The subjective discomfort associated with dry eye and neurologic symptoms were more severe in the VR group than in the smartphone group. There were no significant changes in refraction and choroidal thickness after the use of either of the two devices. The poorer the participants' accommodation and convergence ability the greater the resistance to changes in these visual parameters, and participants with a large exophoria were more prone to worsening of exophoria than those with a small exophoria.

The rate of superior oblique surgery in children and adolescents with Brown syndrome according to claims data.

PURPOSE: To determine the rate of superior oblique surgery and how often it is combined with surgery on other extraocular muscles or associated with subsequent strabismus surgeries in children and adolescents with Brown syndrome. METHODS: This was a population-based retrospective cohort study using the Optum deidentified Clinformatics Data Mart Database (2004-2018) for patients ≤18 years of age diagnosed with Brown syndrome who underwent superior oblique surgery as their first strabismus surgery and had at least 6 months of continuous enrollment. We assessed sex, age, and the number of included patients by year and by age. Combined and subsequent strabismus surgeries were also investigated. RESULTS: Of 1,007 patients diagnosed with Brown syndrome, 115 (11.4%) underwent superior oblique surgery. The rate of superior oblique surgery was relatively constant between 2004 to 2018. The superior oblique surgery rate was highest in children ≤2 years of age with a decreasing rate as age increased. In 45 of 115 patients (39.1%), other extraocular muscles were operated on in addition to the superior oblique muscle. Of 88 patients who underwent superior oblique surgery without concurrent vertical muscle surgery as the first operation, 11 patients (12.5%) subsequently underwent an additional vertical muscle surgery because of newly developed or worsening vertical misalignment. CONCLUSIONS: In this study cohort, superior oblique surgery was performed on 11.4% of children and adolescents with Brown syndrome. The number of patients with Brown syndrome and the rate of superior oblique surgery decreased as age increased to age 10 years.

Incidence of retinal detachment after lens surgery in children and young adults with nontraumatic ectopia lentis.

PURPOSE: To determine the incidence of retinal detachment after lens surgery in children and young adults with nontraumatic ectopia lentis. SETTING: Population-based claims data. DESIGN: Population-based retrospective cohort study. METHODS: Patients with nontraumatic ectopia lentis aged 30 years or younger who had undergone lens surgery with or without intraocular lens (IOL) implantation and had 1 year or greater continuous enrollment after lens surgery were included in the Optum deidentified Clinformatics Data Mart Database (2003 to 2019) and IBM MarketScan Databases (2007 to 2016). Both databases were assessed for sex, age, etiology of ectopia lentis, IOL implantation, and postoperative retinal detachment separately. Univariate and multivariate analyses were conducted to identify the risk factors for postoperative retinal detachment. RESULTS: Among a total of 298 eyes (210 patients), IOL implantation was coupled with lens surgery in 151 eyes (49.8%) that underwent lens surgery for nontraumatic ectopia lentis. The median follow-up was 32 months in aphakic eyes and 29 months in pseudophakic eyes. Patients undergoing IOL implantation were older at the time of lens surgery (median age: no IOL, 6 years; IOL, 16 years; P < .001). Retinal detachment developed in 13 patients (14 eyes [4.7%]) 14 eyes (4.7%). Older age was the baseline characteristic that correlated most closely with the risk for retinal detachment (P = .05). CONCLUSIONS: The rate of retinal detachment was similar with or without IOL implantation after lens surgery for nontraumatic ectopia lentis in children and young adults.

Usefulness of virtual reality-based training to diagnose strabismus.

To study the usefulness of virtual reality (VR)-based training for diagnosing strabismus. Fourteen residents in ophthalmology performed at least 30 VR training sessions to diagnose esotropia and exotropia. Examinations of real patients with esotropia or exotropia before and after the VR training were video-recorded and presented to a strabismus expert to assess accuracy and performance scores for measuring the deviation angle and diagnosing strabismus with anonymization. A feedback survey regarding the usefulness and ease of use of the VR application was conducted for participants. The mean age of the 14 ophthalmology residents (10 men and 4 women), was 29.7 years. Before VR training, participants showed a mean accuracy score of 14.50 ± 5.45 and a performance score of 9.64 ± 4.67 for measuring the deviation angle and diagnosing strabismus in real patients with strabismus. After VR training, they showed a significantly improved accuracy score of 22.14 ± 4.37 (p = 0.012) and a performance score of 15.50 ± 1.99 (p = 0.011). According to the survey, most participants agreed on the usefulness of VR applications. This study suggests that VR-based training improved ophthalmology residents' clinical diagnostic skills for strabismus in a short period.

Automated assessment of the substantia nigra on susceptibility map-weighted imaging using deep convolutional neural networks for diagnosis of Idiopathic Parkinson's disease.

OBJECTIVES: Despite its use in determining nigrostriatal degeneration, the lack of a consistent interpretation of nigrosome 1 susceptibility map-weighted imaging (SMwI) limits its generalized applicability. To implement and evaluate a diagnostic algorithm based on convolutional neural networks for interpreting nigrosome 1 SMwI for determining nigrostriatal degeneration in idiopathic Parkinson's disease (IPD). METHODS: In this retrospective study, we enrolled 267 IPD patients and 160 control subjects (125 patients with drug-induced parkinsonism and 35 healthy subjects) at our institute, and 24 IPD patients and 27 control subjects at three other institutes on approval of the local institutional review boards. Dopamine transporter imaging served as the reference standard for the presence or absence of abnormalities of nigrosome 1 on SMwI. Diagnostic performance was compared between visual assessment by an experienced neuroradiologist and the developed deep learning-based diagnostic algorithm in both internal and external datasets using a bootstrapping method with 10000 re-samples by the "pROC" package of R (version 1.16.2). RESULTS: The area under the receiver operating characteristics curve (AUC) (95% confidence interval [CI]) per participant by the bootstrap method was not significantly different between visual assessment and the deep learning-based algorithm (internal validation, .9622 [0.8912-1.0000] versus 0.9534 [0.8779-0.9956], P = .1511; external validation, 0.9367 [0.8843-0.9802] versus 0.9208 [0.8634-0.9693], P = .6267), indicative of a comparable performance to visual assessment. CONCLUSIONS: Our deep learning-based algorithm for assessing abnormalities of nigrosome 1 on SMwI was found to have a comparable performance to that of an experienced neuroradiologist.

Effect of age on reoperation rate in children undergoing exotropia surgery.

PURPOSE: To determine the effect of age on the reoperation rate in children undergoing exotropia surgery. METHODS: This was a population-based retrospective cohort study using claims data that included children ≤ 12 years who had undergone exotropia surgery as the first strabismus operation and had ≥ 3 years of continuous enrolment were selected from the Optum de-identified Clinformatics Data Mart Database (2003-2019). Patient age at the first exotropia surgery was grouped into three categories; 0-3, 4-6, and 7-12 years. We assessed the sex, race, age, surgical methods, continuous enrolment period after the first surgery, and the time between the first surgery and reoperation. Cox regression analysis was used to estimate the risk of reoperation at different ages. The hazard ratio of reoperation in children undergoing exotropia surgery according to the age at the first exotropia surgery. RESULTS: Among 2015 children, 312 (15.5%) underwent one or more reoperations. A reoperation was more often performed for recurrent exotropia (n = 231) than for consecutive esotropia (n = 81). The time between the first surgery and reoperation was shorter for reoperation for consecutive esotropia (376 days) than for recurrent exotropia (672 days) (p < 0.001). Younger children showed a higher reoperation hazard ratio than older children (p < 0.001). In reoperation for consecutive esotropia, the patients aged 0-3 years showed a high hazard ratio (2.82; 95% CI, 1.59-5.01). CONCLUSION: Children undergoing exotropia surgery at a younger age have a higher reoperation rate than those undergoing surgery at an older age.

Long-term outcomes of prediction error after combined phacoemulsification and trabeculectomy in glaucoma patients.

BACKGROUND: To investigate long-term outcomes of prediction error after phacotrabeculectomy and to determine risk factors that may cause unstable prediction error after phacotrabeculectomy in glaucoma patients. METHODS: A total 120 eyes of 120 patients who had underwent uncomplicated phacotrabeculectomy (combined group) or phacoemulsification (phaco-only group) were included. Best-corrected visual acuity (BCVA), intraocular pressure (IOP) were measured before and after surgery, and anterior segment parameters including anterior chamber depth (ACD), lens vault (LV), and anterior vault (AV) measured using anterior-segment optical coherence tomography were compared between the two groups. The mean absolute error (MAE) at 3, 6, 12, and 24 months postoperatively were compared. Risk factors associated with unstable prediction error (MAE ≥ 0.5) were investigated in the combined group. RESULTS: In both groups, BCVA was improved and IOP was decreased significantly. MAE at 3, 6, 12, 24 months postoperatively were not significantly different between two groups. The risk factors for unstable prediction error after 12 months of phacotrabeculectomy were old age and LV. Whereas, the only factor predicting unstable prediction error after 24 months of phacotrabeculectomy was LV. The cut-off value of LV for predicting unstable refractive error analyzed by the ROC curve was 0.855 mm. CONCLUSIONS: Phacotrabeculectomy may be an effective treatment with stable long-term outcomes of prediction error similar to phacoemulsification in patients with glaucoma. However, elderly patients or patients with large LV may be predisposed to unstable prediction error after phacotrabeculectomy.

Anterior Scleral Thickness in Myopic Eyes and Its Association with Ocular Parameters.

PURPOSE: This study was designed to determine whether the anterior scleral thickness is affected by axial elongation and to investigate the association between anterior scleral thickness and various ocular parameters in myopic eyes. METHODS: This cross-sectional study included 79 healthy myopic participants. Anterior scleral thickness was measured in 8 meridians (superior-nasal, superior, superior-temporal, temporal [T], inferior-temporal, inferior [I], inferior-nasal, and nasal [N]) using anterior segment optical coherence tomography. Bruch's membrane opening (BMO) area, width of ß-parapapillary atrophy with and without Bruch's membrane (PPA+BM and PPA-BM), and the global peripapillary and subfoveal choroidal thickness were additionally measured. Age- and sex-adjusted partial correlation analysis and linear regression analysis were performed to examine the effects of axial length and various ocular parameters on anterior scleral thickness in myopic eyes. RESULTS: The mean age of the included participants was 27.03 ± 2.70 years. Overall, the anterior scleral thickness varied topographically according to the meridians and distance from the scleral spur. In the partial correlation analysis controlled for the effect of age and sex, increasing axial length was related to anterior scleral thinning at several measurement points along the T, I, and N meridians. Among the several ocular parameters, multivariate linear regression analysis with age, sex, and axial length as covariates revealed that central corneal thickness, intraocular pressure, and BMO area were significantly associated with anterior scleral thickness. CONCLUSION: In conclusion, there was a close relationship between the anterior scleral thickness and several ocular parameters in myopic eyes. These features should be taken into consideration when managing myopia, and our results might have important implications for understanding the pathogenesis of scleral changes during axial elongation.

Influence of virtual reality on visual parameters: immersive versus non-immersive mode.

BACKGROUND: To investigate the differences in refraction, accommodative factors, visual parameters, and subjective symptoms after using two types of virtual reality (VR) content with different depths of perception. METHODS: Twenty-three volunteers, who played VR games in two modes (immersive and non-immersive) for 30 min, were enrolled. Visual parameters were examined before and after using VR. Accommodative factors were measured using static and dynamic methods. Subjective symptoms were assessed using a questionnaire. Differences according to VR content were compared, and correlations between each visual parameter were analyzed. RESULTS: There were no changes in refraction or accommodative factors after use of the VR. However, there was a significant increase in the near point of accommodation (NPA), the near point of convergence (NPC), and subjective symptom scores after using the immersive mode. Correlation analysis revealed a positive correlation between baseline values of near exophoria and mean accommodative lag of the dominant eye, and also revealed a negative correlation between NPA and mean accommodative lag in the non-dominant eye. CONCLUSIONS: The use of VR for 30 min increased NPA and NPC, especially after the immersive mode was used. In addition, higher exophoria and smaller NPA is associated with increased accommodative lag after using VR.

Parapapillary atrophy and changes in the optic nerve head and posterior pole in high myopia.

We investigated the relationship between microstructure of ß-parapapillary atrophy (ß-PPA) and morphologic features of optic nerve head (ONH) and posterior pole in highly myopic eyes. Eighty-nine highly myopic eyes were included in this study. Bruch's membrane opening (BMO) area, lamina cribrosa (LC) thickness, anterior laminar depth, peripapillary and subfoveal choroidal thickness (CT), macular Bruch's membrane (BM) length, and width of ß-PPA with and without Bruch's membrane (PPA+BM and PPA-BM) were evaluated. The mean age and axial length of the included subjects were 26.88 ± 2.44 years and 27.03 ± 0.88 mm, respectively. The width of PPA-BM was larger with increasing BMO area (P = 0.001), whereas the BMO area was not associated with the width of PPA+BM. The large PPA+BM was significantly related to a thinner LC (P = 0.003), deeper anterior lamina surface (P < 0.001), longer macular BM length (P = 0.008), and thinner temporal peripapillary CT (P = 0.034). We found that the morphologic features of the ONH and posterior pole in highly myopic eyes were different based on the microstructure of ß-PPA. Whether these features are linked to the development of glaucoma in myopic eyes should be investigated in future studies.

Impaired DNA-binding affinity of novel PAX6 mutations.

Mutations in human PAX6 gene are associated with various congenital eye malformations including aniridia, foveal hypoplasia, and congenital nystagmus. These various phenotypes may depend on the mutation spectrums that can affect DNA-binding affinity, although this hypothesis is debatable. We screened PAX6 mutations in two unrelated patients with congenital nystagmus, and measured DNA-binding affinity through isothermal titration calorimetry (ITC). To elucidate phenotypic differences according to DNA-binding affinity, we also compared DNA-binding affinity among the previously reported PAX6 missense mutations within the linker region between two subdomains of the paired domain (PD). We identified two novel mutations of PAX6 gene: c.214 G > T (p.Gly72Cys) and c.249_250delinsCGC (p.Val84Alafs*8). Both were located within the linker region between the two subdomains of the PD. ITC measurement revealed that the mutation p.Val84Alafs*8 had no DNA-binding affinity, while the p.Gly72Cys mutation showed a decreased binding affinity (Kd = 0.58 µM) by approximately 1.4 times compared to the wild type-PAX6 (Kd = 0.41 µM). We also found that there was no close relationship between DNA-binding affinity and phenotypic differences. Our results suggest that the DNA-binding affinity alone might be insufficient to determine PAX6-related phenotypes, and that other modifier genes or environmental factors might affect phenotypes of the PAX6 gene.

Virtual reality-based measurement of ocular deviation in strabismus.

BACKGROUND AND OBJECTIVE: Strabismus is an eye movement disorder in which shows the abnormal ocular deviation. Cover tests have mainly been used in the clinical diagnosis of strabismus for treatment. However, the whole process depends on the doctor's level of experience, which could be subjected to several factors. In this study, an automated technique for measurement of ocular deviation using a virtual reality (VR) device is developed. METHODS: A VR display system in which the screens that have the fixation target are changed alternately between on and off stages is used to simulate the normal strabismus diagnosis steps. Patients watch special-designed 3D scenes, and their eye motions are recorded by two infrared (IR) cameras. An image-processing-based pupil tracking technique is then applied to track their eye movement. After recording eye motion, two strategies for strabismus angle estimation are implemented: direct measurement and stepwise approximation. The direct measurement converts the eye movement to a strabismus angle after considering the eyeball diameter, while the stepwise approximation measures the ocular deviation through the feedback calibration process. RESULTS: Experiments are carried out with various strabismus patients. The results are compared to those of their doctors' measurement, which shows good agreement. CONCLUSIONS: The results clearly indicate that these techniques could identify ocular deviation with high accuracy and efficiency. The proposed system can be applied in small space and has high tolerance for the unexpected head movements compared with other camera-based system.

Neuroprotective Effect of Brazilian Green Propolis on Retinal Ganglion Cells in Ischemic Mouse Retina.

PURPOSE: The current study was undertaken to investigate whether Brazilian green propolis (BGP) can increase the viability of retinal ganglion cells (RGCs) in ischemic mouse retina, and examined the possible mechanisms underlying this neuroprotection. MATERIALS AND METHODS: C57BL/6J mice were subjected to constant elevation of intraocular pressure for 60 min to establish retinal ischemia-reperfusion injury. Mice then received saline or BGP (200 mg/kg) intraperitoneally once daily until sacrifice. The expression of hypoxia-inducing factor (HIF)-1α and glial fibrillary acidic protein (GFAP) and the level of histone acetylation were assessed at 1, 3, and 7 days after injury. The expression of Bax, Bcl-2, p53, NF-κB, Nrf2, and HO-1 were also analyzed at 3 days after injury. The neuroprotective effect of BGP treatment on RGC survival was evaluated using Brn3a immunohistochemical staining. RESULTS: The expression of HIF-1α and GFAP was increased and the level of histone acetylation decreased in saline-treated ischemic retinas within 7 days. BGP treatment effectively attenuated the elevated expression of HIF-1α, GFAP, Bax, NF-κB and p53. The expression of Bcl-2, Nrf2, HO-1 and the level of histone acetylation increased by BGP treatment, resulting in a significant difference between BGP-treated and saline-treated retinas. Immunohistochemical staining for Brn3a also revealed that BGP treatment protected against RGC loss in ischemic retina. CONCLUSIONS: Our results suggest that BGP has a neuroprotective effect on RGCs through the upregulation of histone acetylation, downregulation of apoptotic stimuli, and suppression of NF-κB mediated inflammatory pathway in ischemic retina. These findings suggest that BGP is a potential neuroprotective agent against RGC loss under oxidative stress.