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The red reflex test, performed using a direct ophthalmoscope, serves as a critical diagnostic tool in identifying various ocular conditions. These conditions encompass retinal anomalies (such as retinoblastoma, Coats disease, retinopathy of prematurity, familial exudative vitreoretinopathy, myelinated nerve fibers, ocular toxocariasis, ocular toxoplasmosis, retinochoroidal coloboma, astrocytic, and combined hamartoma), vitreous abnormalities (including persistent fetal vasculature), lens issues (like cataract), anterior chamber and corneal conditions (comprising dysgenesis of the anterior segment, congenital glaucoma, birth trauma), and tear film disturbances. During this examination, the presence of leukocoria, characterized by a white pupillary reflex, can suggest the presence of underlying conditions. Any suspicion of an abnormal red reflex test warrants immediate evaluation by a qualified ophthalmologist. This article primarily underscores the paramount importance of the red reflex examination, not only to identify potential sight-threateningbut also life-threatening conditions. It delves into the most common causes of leukocoria in childhood and offers insights into a comprehensive diagnostic approach. The target audience for this article includes pediatricians, primary care clinicians, and ophthalmologists, all of whom play a pivotal role in the early detection and intervention of these critical eye disorders.

Pierson syndrome (PS) is a rare autosomal recessive disease, characterized by congenital nephrotic syndrome (CNS), and ocular and neurologic abnormalities. In affected cases, there is abnormal b-2 laminin which is compound of the several basement membranes caused by inherited mutations in the LAMB2 gene. Although patients have mutations in the same gene, the phenotype is highly variable. In this case series, the relationship between genotype and phenotype is emphasized, and information about the clinical follow-up of the patients is presented. Hereby, we report four pediatric cases with PS as a result of mutation in the LAMB2 gene. Clinical spectrum of LAMB2-associated disorders varies from mild-to-severe ocular, kidney, and neurologic involvement. Since genotype-phenotype correlation in PS has not been clearly demonstrated, we recommend that all patients with ophthalmic anomalies and glomerular proteinuria should be tested for LAMB2 mutations., (© 2023. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Background: To evaluate the frequency and anterior segment optical coherence tomography parameters of patients with scleral fixated intraocular lenses (IOL) and reverse pupillary block (RPB)., Methods: Retrospective analysis at a tertiary care centre (Department for Ophthalmology and Optometry, Medical University of Vienna, Austria). We researched our records for patients who underwent scleral fixated IOL implantation from January 2018 till February 2023. Patients were included only if there was at least one adequate post-operative scan of anterior segment optical coherence tomography (AS-OCT) available. Initially, AS-OCT scans were assessed for IOL tilt and decentration employing a 3D scan and then later for anterior chamber angle (ACA), aqueous anterior chamber depth (AQD), pupil diameter and iris-IOL distance using the 2D scan at a 0° angle. Both an iris-IOL distance of 0 or less and an ACA of more than 70° were required to define an RPB., Results: A total of 110 patients met the inclusion criteria, 41 were treated using the Carlevale, 33 the four flanged, 24 the Yamane and 12 the Scharioth technique, respectively. RPB was found in 32 patients (29%). Twenty patients with RPB were treated using YAG peripheral iridotomy, mean ACA decreased from 91.91° ± 13.77 to 61.02° ± 8.52, (p < 0.001), mean AQD decreased from 4.67 mm ± 0.47 to 4.31 ± 0.36 mm (p < 0.001) and mean iris-IOL distance increased from -0.09 ± 0.04 to 0.33 ± 0.30 (p < 0.001)., Conclusions: RPB is found in a third of eyes who have undergone scleral fixated IOL implantation without iridectomy. YAG peripheral iridotomy is a potent option to treat RPB, and subsequently reduce the risk of iris chafing and secondary inflammation or glaucoma., (© 2024 The Authors. Clinical & Experimental Ophthalmology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Ophthalmologists.)

A healthy 4-year-old boy referred for evaluation of an abnormal red reflex in the left eye was noted, on fundus examination, to have extensive white, striated lesions surrounding the optic nerve that involved the superior and inferior macular arcades. On further examination, he was found to have ipsilateral high myopia and amblyopia. The triad of unilateral myelinated retinal nerve fibers, myopia, and amblyopia led to a diagnosis of Straatsma syndrome, which requires early treatment to prevent permanent vision loss. Treatment comprised a contact lens for refractive correction of the left eye, patching of the right eye, and full-time polycarbonate protective lenses. With 2 years' follow-up, the left eye failed to improve appreciably., (Copyright ©2024. All rights reserved. Reproduction in whole or in part in any form or medium without expressed written permission of the Digital Journal of Ophthalmology is prohibited.)

Background: Ectopia lentis is the dislocation of the natural crystalline lens and usually presents in the setting of trauma or other systemic diseases. Herein, we describe a case of an otherwise healthy four-year-old boy with isolated ectopia lentis whose partial lens dislocation was captured on a smartphone by the patient's father several days prior., Case Presentation: A four-year-old boy with no past medical, developmental, or trauma history presented with bilateral partial anterior lens dislocation with pupillary block. Initial ophthalmic evaluation two months prior was notable for uncorrected visual acuity at 20/100 OD, 20/250 OS, bilateral iridodenesis, and partially dislocated lenses inferonasally OD and inferiorly OS on slit lamp. Genetic testing found no abnormalities. Ten months later, the patient developed sudden onset of left eye pain. A dislocated lens and temporarily dilated left pupil were captured on a smartphone by the patient's father. He was evaluated 3 days later after a second episode and found to have hand motion vision OS, a fixed 8 mm left pupil with the crystalline lens subluxed into the pupil space and accompanying intraocular pressure OS of 40 mmHg. The lens was surgically removed with a limited anterior vitrectomy. Four and a half years after surgery, visual acuity was 20/125 OS with aphakic correction. The right eye eventually underwent prophylactic lensectomy and was 20/30 in aphakic correction., Conclusions: This report presents a unique presentation of isolated ectopia lentis with anterior lens dislocation and pupillary block and illustrates the role of smartphone photography in assisting in the triage of eye emergencies., (© 2024. The Author(s).)

Competing Interests: The authors report no conflicts of interest.

Purpose: By comparing the results of the new self-contained darkroom refractive screener (YD-SX-A) versus table-top autorefractor and cycloplegic retinoscopy, to evaluate the performance of the YD-SX-A in detecting refractive error in children and adolescents and then judge whether it can be used in refractive screening., Methods: Cross-sectional study. 1000 participants between the ages of 6 and 18 who visited the Optometry Center of the People's Hospital of Guangxi Zhuang Autonomous Region from June to December 2022 were selected. First, participants were instructed to measure their diopter with a table-top autorefractor (Topcon KR8800) and YD-SX-A in a noncycloplegic setting. After cycloplegia, they were retinoscopy by a professional optometrist. The results measured by three methods were collected respectively. To avoid deviation, only the right eye (1000 eyes) data were used in the statistical analysis. The Bland-Altman plots were used to evaluate the agreement of diopters measured by the three methods. The receiver operating characteristic (ROC) curves was used to analysis effectiveness of detecting refractive error of YD-SX-A., Results: The average age of participants was 10.77 ± 3.00 years, including 504 boys (50.4%) and 496 girls (49.6%). When YD-SX-A and cycloplegia retinoscopy (CR) were compared in the myopia group, there was no statistical difference in spherical equivalent (SE) (P > 0.05), but there was a statistical difference in diopter spherical (DS) and diopter cylinder (DC) (P < 0.05). Comparing the diopter results of Topcon KR8800 and CR, the difference between each test value in the myopia group was statistically significant (P < 0.05). In the hyperopia group, the comparison between YD-SX-A and CR showed no statistically significant differences in the DC (P > 0.05), but there were significant differences in the SE and DS (P < 0.05). In the astigmatism group, the SE, DS, and DC were statistically different, and the DC of YD-SX-A was lower than that of CR and Topcon KR8800. Bland-Altman plots indicated that YD-SX-A has a moderate agreement with CR and Topcon KR8800. The sensitivity and specificity of YD-SX-A for detecting myopia, hyperopia and astigmatism were 90.17% and 90.32%, 97.78% and 87.88%, 84.08% and 74.26%, respectively., Conclusion: This study has identified that YD-SX-A has shown good performance in both agreement and effectiveness in detecting refractive error when compared with Topcon KR8800 and CR. YD-SX-A could be a useful tool for large-scale population refractive screening., (© 2023. The Author(s).)

Significance: Objective pupillometry with standardized light intensities allows a comprehensive assessment of the relative afferent pupillary defect in patients with unilateral neuro-ophthalmic pathology., Purpose: This study aimed to determine the impact of varying light intensities on the grade of relative afferent pupillary defect in unilateral neuro-ophthalmic pathology vis-à-vis healthy controls., Methods: Monocular pupillary light reflexes of 20 controls (14 to 50 years) and 31 cases (12 to 72 years) with clinically diagnosed relative afferent pupillary defect were measured thrice using 1-second-long light pulses, followed by 3 seconds of darkness, at eight light intensities (6.4 to 1200 lux) using objective pupillometry. The relative afferent pupillary defect was quantified as the ratio of the percentage change in the direct light reflexes of the left and right eyes. Its change with light intensity was described using standard exponential fits., Results: The median (25th to 75th interquartile range) defect score of 54.8% cases decreased from baseline values of 1.58 (1.25 to 1.87) for right eye pathology and 0.45 (0.39 to 0.55) for left eye pathology to saturation values of 1.18 (1.05 to 1.31) and 0.98 (0.95 to 1.06), respectively, at light intensities between 56.9 and 300.5 lux. Like controls (1.01 [1.00 to 1.06]), the defect scores of the remaining 45.2% cases were constant with light intensity at 1.23 (1.18 to 1.46) and 0.87 (0.86 to 0.89) for right and left eye pathologies, respectively., Conclusions: Relative afferent pupillary defects may decrease with test light intensity in a significant proportion of patients with unilateral neuro-ophthalmic pathology. This highlights the importance of objective pupillometry with standardization light intensities for clinical assessment of afferent pupillary defects., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2023 American Academy of Optometry.)

Pupil abnormalities may be physiological, pathological or pharmacological. It can indicate the underlying disease of the visual afferent system or visual efferent system. Examination of the pupils is therefore a part of eye examination. Insufficient knowledge and inconsistent methods in the pupillary examination by some ophthalmologists lead to mistakes or unreliable results, hampering the disease diagnosis and clinical assessment. This article emphasizes the significance of pupillary examination outcomes, advocates for standardized examination methods, and highlights the need to enhance the awareness of pupillary abnormalities, aiming to provide a guide on how to recognize and interpret the clinical implications of pupillary abnormalities, and to offer valuable insights for clinical practice.

Background: The swinging flashlight test (SFT) is one of the most prominent clinical tests for detecting the relative afferent pupillary defect (RAPD). A positive RAPD localizes the lesion to the affected afferent pupil pathway and is a critical part of any ophthalmic exam. Testing for an RAPD, however, can be challenging (especially when small), and there is significant intrarater and interrater variability., Methods: Prior studies have shown that the pupillometer can improve the detection and measurement of RAPD. In our previous research, we have demonstrated an automatic SFT by utilizing virtual reality (VR), named VR-SFT. We applied our methods to two different brands of VR headsets and achieved comparable results by using a metric, called RAPD score, for differentiating between patients with and without (control) RAPD. We also performed a second VR-SFT on 27 control participants to compare their scores with their first assessments and measure test-retest reliability of VR-SFT., Results: Even in the absence of any RAPD positive data, the intraclass correlation coefficient produces results between 0.44 and 0.83 that are considered of good to moderate reliability. The same results are echoed by the Bland-Altman plots, indicating low bias and high accuracy. The mean of the differences of measurements from test-retest ranges from 0.02 to 0.07 for different protocols and different devices., Conclusions: As variability among various VR devices is an important factor that clinicians should consider, we discuss the test-retest reliability of VR-SFT and the variability among various assessments and between two devices., Translational Relevance: Our study demonstrates the critical necessity of establishing test-retest reliability measures when bridging virtual reality technology into the clinical setting for relevant afferent pupillary defect.

Background: Pseudophakic pupillary block (PPB) was rare in patients who undergo phacoemulsification and posterior chamber intraocular lens (PCIOL) implantation. Laser peripheral iridotomy was the most reported but ineffective treatment in the literature., Methods: Retrospective, interventional case series of patients who developed PPB in Taipei Veterans General Hospital from 2017 to 2021. Clinical course, diagnostic methods, treatment and outcomes were recorded and discussed., Results: Four eyes of three patients were documented. All of them had diabetes and diabetic retinopathy. Anterior segment Optical coherence tomography (OCT) of these patients showed an exudative membrane at the peripapillary area while slit lamp image could not provide a clear view due to the severely edematous corneal condition. Laser peripheral iridotomy and yttrium aluminum garnet (YAG) laser aiming to the peripapillary exudation were applied to break the PPB successfully., Conclusion: Diabetes mellitus, intravitreal injection and inflammation are crucial risk factors for PPB. Anterior segment OCT can be a useful diagnostic tool for the detection of the peripapillary exudative membrane while corneal clarity is compromised due to high intraocular pressure. In addition to peripheral laser iridotomy, an effective approach to resolve PPB may be the use of the YAG laser to break the exudative membrane., Competing Interests: Declaration of Competing Interest All authors have declared no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: To determine the retinal nerve fiber layer (RNFL) thickness and ganglion cell complex (GCC) thickness in patients having relative afferent pupillary defect (RAPD) measured by optical coherence tomography (OCT)., Methods: This cross-sectional study was conducted on 30 patients with posterior segment disease and glaucoma presenting with RAPD. The control group comprised 30 patients with the aforementioned diseases without RAPD. RAPD was graded using neutral density filters placed over the unaffected eye. Peripapillary RNFL thickness and macular GCC were measured using the Cirrus HD-OCT machine., Results: There were 45 males and 15 females. There was a statistically significant (P < 0.05) difference in the mean of average RNFL thickness in patients having RAPD (64.73 ± 15.16 μm in the affected eyes) as compared to sick control (82.73 ± 11.33 μm in the affected eyes). It was further observed that there was a decrease in RNFL thickness with advancing grades of RAPD. There was a statistically significant (P < 0.05) difference in the mean of average GCC thickness in patients having RAPD (51.57 ± 14.96 μm in the affected eyes) as compared to sick control (76.36 ± 8.06 μm in the affected eyes)., Conclusion: Our study suggests that there is a significant reduction in RNFL thickness and GCC thickness in RAPD patients as compared to the sick control group., Competing Interests: None

Paradoxical pupillary reaction (initial pupillary constriction to darkness) has been most associated with the inherited retinal disorders congenital stationary night blindness and achromatopsia. However, underlying genotypes and associations with other pediatric retinal phenotypes are not well documented. A retrospective review for paradoxical pupillary reaction was performed at the Ocular Genetics Clinic of Cleveland Clinic Abu Dhabi (2016-2020). Four children from 4 different families were identified, all of whom had had genetic confirmation of the clinical diagnosis. Associated pathogenic variants were in TRPM1 (biallelic; two boys; congenital stationary night blindness), CABP4 (biallelic; one boy, congenital cone-rod synaptic disorder) and PAX2 (monoallelic; one girl, papillorenal syndrome). Genetically confirmed affected relatives of the 2 probands with TRPM1-related congenital stationary night blindness did not show the phenomenon. This study documents novel genotypes and phenotypes that can be associated with paradoxical pupillary reaction in children and confirms potential intrafamilial variable expressivity for the phenomenon., (Copyright © 2022 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the correlations between relative afferent pupillary defect (RAPD) magnitude, assessed using the clinical plus scale and neutral density filters, and visual field parameters in patients with unilateral or asymmetrical bilateral optic neuropathy or retinopathy., Methods: Fifty-two patients with RAPD, graded by the swinging flashlight test and neutral density filters, were analyzed in this cross-sectional trial. The RAPD clinical plus scale was divided into grade 1+, initial weak constriction; grade 2+, initial stall then dilatation; grade 3+, immediate dilatation; and grade 4+, fixed amaurotic pupil. Patients with positive RAPD underwent a visual field examination with Humphrey automated perimetry that included visual field index (VFI), mean deviation (MD), and pattern standard deviation (PSD). Spearman's rank correlation coefficients and linear regression were used to analyze the association between RAPD grades and visual field parameters., Results: RAPD clinical plus grades were correlated with interocular VFI (r = 0.55, P < 0.001) and MD (r = 0.48, P = 0.004) differences. Average interocular VFI differences were estimated as follows: 16.75 × RAPD plus grade- 7.53. RAPD, graded by neutral density filters, was correlated with VFI (r = 0.59, P < 0.001), MD (r = 0.54, P < 0.001), and PSD (r = 0.34, P = 0.01)., Conclusions: The RAPD plus scale and neutral density filter grading systems were associated with quantitative visual field defect parameters, with VFI showing the strongest association. RAPD clinical grading could substitute more sophisticated central visual field evaluation methods as a low-cost, low-tech, and widely available approach., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To examine systematically how prechiasmal, chiasmal, and postchiasmal lesions along the visual pathway affect the respective pupillary responses to specific local monochromatic stimuli., Methods: Chromatic pupil campimetry (CPC) was performed in three patient groups (10 subjects with status after anterior ischemic optic neuropathy, 6 with chiasmal lesions, and 12 with optic tract or occipital lobe lesions (tumor, ischemia)) using red, low-intensity red, and blue local stimuli within the central 30° visual field. Affected areas - as determined by visual field defects revealed using conventional static perimetry - were compared with non-affected areas. Outcome parameters were the relative maximal constriction amplitude (relMCA) and the latency to constriction onset of the pupillary responses., Results: A statistically significant relMCA reduction was observed in the affected areas of postchiasmal lesions with red (p = 0.004) and low-intensity red stimulation (p = 0.001). RelMCA reduction in the affected areas seemed more pronounced for low-intensity red stimulation (46.5% mean reduction compared to non-affected areas; 36% for red stimulation), however statistically not significant. In prechiasmal lesions, a statistically significant latency prolongation could be demonstrated in the affected areas with low-intensity red stimulation (p = 0.015)., Conclusion: Our results indicate that the choice of stimulus characteristics is relevant in detecting defects in the pupillary pathway of impairment along the visual pathway, favoring red stimuli of low intensity over blue stimuli. Such knowledge opens the door for further fundamental research in pupillary pathways and is important for future clinical application of pupillography in neuro-ophthalmologic patients., (© 2021. The Author(s).)

The authors describe a challenging case of unilateral retinoblastoma in a patient referred for xanthocoria. A 3-year-old boy was referred for unilateral xanthocoria and disordered retinal vasculature, suggestive of Coats disease. Further investigation revealed diffuse subretinal tumor seeding and areas of calcification, consistent with retinoblastoma. Enucleation was performed and histopathology confirmed exophytic retinoblastoma. This case highlights that xanthocoria, although often encountered in patients with Coats disease, can sometimes be associated with retinoblastoma. As such, retinoblastoma should be considered in the differential diagnosis for children with both leukocoria and xanthocoria. [ J Pediatr Ophthalmol Strabismus. 2022;59(X):e32-e34.] .

Background: Leukocoria means white pupil. Normal pupil appears black in children and adults. The typical red reflex is due to retro-illumination of choroidal vessels reflected via the retina, vitreous humor, crystalline lens, aqueous humor, pupil, and cornea. If there is interference in these structures, it would result in a changed red reflex, or leukocoria. Immediate family members are highly likely to detect the first indicator and the pediatrician or general ophthalmologist is usually the first to be visited. The aim of the study was to find out the prevalence of common causes of white pupillary reflex in children, to undertake early diagnosis and treatment, and to reduce morbidity and death. This study aimed to see how common it is for children to have a white pupillary reflex when they visit a pediatric ophthalmologist. Objective: Determine the incidence of conditions that cause a white pupillary reflex in children who visited Hayatabad Medical Complex Hospital in Peshawar. Materials and methods: This study was carried out in the Ophthalmology unit of HMC Hospital Peshawar, from January 2021 to December 2021. 168 patients were enrolled in the study. We included all patients of up to 10 years and both genders with the above findings. Workup for leukocoria was done to find the exact cause that included fundoscopy, B-Scan, MRI, and CT scans. Examination under anesthesia (EUA) was carried out for uncooperative children for detailed fundus examination. Patient data was recorded and a proforma was made to collect all the necessary information. Family history was taken in detail during this study. Results: The most common cause of aberrant pupillary reflex in children aged 1 to 10 years was cataract, 79.76 percent of patients having it. Retinoblastoma (12.5%), Coats disease (3.5%), retinal detachment (2.9%) and persistent hyperplastic vitreous (PHPV) (1.1%) were other notable causes found. Conclusion: Leukocoria is a critical clinical finding, and if parents or primary care physicians notice it, the patient requires a complete follow-up examination by a pediatric ophthalmologist to determine the etiology., (© The Authors.Romanian Society of Ophthalmology.)

Purpose: The occurrence of relative afferent pupillary defect (RAPD) secondary to optic nerve diseases and widespread retinal disorders is well established. However, only very few reports of RAPD in macular disorders exist in the literature. In this study, we used automated pupillometer to evaluate RAPD in eyes with macular lesions., Methods: It was a prospective cross-sectional study. A total of 82 patients with choroidal neovascular membrane (CNVM) - 65 unilateral and 17 bilateral macular lesions - were enrolled. RAPD was assessed with an automated pupillometer and macular lesions evaluated with optical coherence tomography (OCT). The length of the ellipsoid zone disruption was measured as the longest length of lesion on the horizontal raster scans and the area of macular lesion was measured manually, mapping the affected area of ellipsoid zone on the enface images., Results: : RAPD scores showed good correlation with the intereye difference in length of maximum ellipsoid zone disruption (r-value = 0.84, P value <0.001) and macular lesion area as measured on OCT in all unilateral cases (r-value = 0.84, P value <0.001). Best-corrected visual acuity was also found to have a significant correlation with lesion size on the OCT as well as the length of ellipsoid zone disruption in unilateral cases., Conclusion: : RAPD evaluated with an automated binocular pupillometer is a noninvasive and objective method to assess macular lesions in CNVMs; it shows good correlation with structural lesion dimensions on OCT in unilateral cases. Further longitudinal studies are needed to assess the significance of these findings in disease progression as well as correlation with lesion response to treatment., Competing Interests: None

Background: Systemic sclerosis (SSc) is a connective tissue disease that may affect the heart and the autonomic nervous system (ANS). There is little knowledge regarding the degree of ANS involvement in SSc patients with unknown cardiac disease., Objectives: To evaluate cardiac and pupillary autonomic functions in patients before cardiac involvement has emerged., Methods: The study comprised 19 patients with SSc and 29 healthy controls. Heart rate variability (HRV) analysis for time and frequency domains, as well as deep breathing test and Ewing maneuvers, were performed in all patients. Automated pupillometry for the evaluation of pupillary diameter and pupillary light reflex was completed in 8 SSc patients and 21 controls., Results: Both groups had similar characteristics, except for medications that were more commonly or solely prescribed for SSc patients. Compared with control subjects, the SSc patients had significantly lower HRV parameters of NN50 (15.8 ± 24.4 vs. 33.9 ± 33.1, P = 0.03), pNN50 (4.9 ± 7.4% vs.10.8 ± 10.8%, P = 0.03), and triangular index (11.7 ± 3.4 vs. 15.7 ± 5.8, P = 0.02). Abnormal adaptive responses in heart rate changes were recorded during deep breathing tests and Ewing maneuvers. There was no significant difference in any of the pupillometric indices or other HRV parameters within groups., Conclusions: SSc patients may manifest cardiac autonomic dysfunction, while their autonomic pupillary function is seemingly spared. The role of certain medications, the significance of differential organ involvement, as well as the prognostic value of our findings should be evaluated in future studies.

Background: Both Pierson syndrome (PS) and isolated nephrotic syndrome can be caused by LAMB2 biallelic pathogenic variants. Only 15 causative splicing variants in the LAMB2 gene have been reported. However, the pathogenicity of most of these variants has not been verified, which may lead to incorrect interpretation of the functional consequence of these variants., Methods: Using high-throughput DNA sequencing and Sanger sequencing, we detected variants in a female with clinically suspected PS. A minigene splicing assay was performed to assess the effect of LAMB2 intron 20 c.2885-9C>A on RNA splicing. We also performed the immunohistochemical analysis of laminin beta-2 in kidney tissues., Results: Two novel LAMB2 heteroallelic variants were found: a paternally inherited variant c.2885-9C>A in intron 20 and a maternally inherited variant c. 3658C>T (p. (Gln1220Ter)). In vitro minigene assay showed that the variant c.2885-9C>A caused erroneous integration of a 7 bp sequence into intron 20. Immunohistochemical analysis revealed the absence of glomerular expression of laminin beta-2, the protein encoded by LAMB2., Conclusion: We demonstrated the impact of a novel LAMB2 intronic variant on RNA splicing using the minigene assay firstly. Our results extend the mutational spectrum of LAMB2., (© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Purpose : To report a patient with Pierson syndrome who presented with neovascular glaucoma (NVG) after cataract surgery. Methods : Retrospective case report. Results : A 17-year old monocular female presented with sudden onset of pain and decreased vision in the right eye. On examination, she had intraocular pressure (IOP) of 50 mmHg, aggressive iris neovascularization (NVI) and 3-piece IOL. Fundus examination revealed pale disc with tessellated fundus and parapapillary atrophy. Vascular arcades were vertically stretched with avascular ischemic retina starting from the near periphery. Macula appeared thin and atrophic. An intravitreal injection of 0.05 mg/0.1 ml bevacizumab was given to the right eye followed by Ahmed glaucoma valve (AGV) implantation. Assessment of her brother revealed similar posterior segment changes. A subsequent urine analysis showed proteinuria and high albumin to creatinine ratio. Next-generation sequencing for LAMB2 gene revealed a homozygous c.4573 + 1 G > A variant confirming the diagnosis of Pierson syndrome. Conclusion : This case expands our knowledge on retinal ischemia in the setting of Pierson syndrome. Close monitoring after intraocular surgery is recommended to look for the development of NVG.

Background: Despite automated pupillometry's (AP) improved detection of relative afferent pupillary defects (RAPDs) compared with the Swinging Flashlight Test (SFT), AP remains uncommon in clinical practice. This study examined barriers to routine use of AP in evaluation of acute vision loss., Methods: (1) Ophthalmologists and optometrists' perceptions of AP were captured via electronic survey. (2) Ophthalmologists were presented with clinical vignettes to assess their use of AP in clinical decision-making. (3) Patients presenting with decreased vision to an ophthalmology urgent care clinic underwent manual SFT and AP screening to evaluate ophthalmologists' perceptions of the device., Results: Surveys indicated that clinicians were "neutral" to "somewhat likely" to use AP. In clinical vignettes, more physicians proceeded with workup for optic nerve pathology when presented with an RAPD by AP than SFT (77% vs 26%, P = 0.003). When SFT and AP results were discordant, more physicians proceeded with workup for optic nerve disease when AP was positive and SFT was negative than vice versa (61% vs 18%, P = 0.008). In the clinical study of 21 patients, 50% of RAPDs detected by AP were not detected by SFT, although ophthalmologists rated AP's usefulness as only "neutral" to "somewhat useful.", Conclusion: Clinicians value pupillary examination and trust AP over SFT; however, widespread adoption and perceived value of AP may depend on its impact on clinical outcomes. Within a comprehensive diagnostic device, AP may be an important tool, but is not necessary to screen for optic nerve disease or evaluate acute vision loss., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by North American Neuro-Ophthalmology Society.)

Background: The clinical presentation of reduced pupillary responses in orbital apex syndrome is currently not well understood clinically. The pupillary light reflex (PLR) is determined using dynamic pupillometry., Case Details: A newly diagnosed 35-year-old diabetic female patient had ocular symptoms including orbital pain and ptosis, but no visual loss. Cranial nerve autonomic impairment was identified with dynamic pupillometry and compared with cardiac autonomic activity using heart rate variability (HRV)., Results: PLR showed that pupil size and response were severely affected, with a small resting pupil size, and minimal response to a bright white light flash was seen, due to decreased sympathetic activity. However, HRV showed normal cardiac sympathetic activity., Conclusion: These findings suggest that orbital apex syndrome may lead to changes in pupil size and response due to compression of sympathetic fibers at the apex of the orbit. Quantitative PLR measurements help to reveal relevant information on anatomical reflex pathways., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Purpose: To measure the predictive values of relative afferent pupillary defect (RAPD) assessed semi-quantitatively, and visual acuity (VA) at onset of central retinal vein occlusion (CRVO), for neovascularization., Methods: Retrospective analysis of the TROXHEMO trial that included patients with CRVO within 30 days after the onset. Inclusion criteria were as follows: semi-quantitative RAPD assessment at diagnosis and/or at one month. RAPD was 'severe' if ≥ 0.9 log. Exclusion criteria were as follows: prophylactic panretinal photocoagulation (PRP) before neovascularization., Results: Among the 119 patients enrolled in the main centre, 101 were analysed. 26 had a neovascular complication during the twelve months of follow-up: rubeosis (19), glaucoma (7) and posterior neovascularization (15). The mean time to onset of a neovascular complication was 4.7 months (1 to 12, median 3 months). All the patients who had a neovascular complication had RAPD at first examination or at one month (negative predictive value (NPV) = 100%) but the positive predictive value (PPV) was low (31%, 95% CI [21%; 42%]). The association 'severe RAPD or VA < 35 letters (ETDRS) at inclusion or at one month' was the best compromise between PPV (53%, [39%; 68%]) and NPV (96%, [92%; 100%])., Conclusion: To predict neovascularization, RAPD should be routinely evaluated with filters: the risk of neovascular complication is (a) almost nil if there is no RAPD, (b) very low if there is no severe RAPD and if VA is higher than 35 letters, and (c) higher than 50% if RAPD is ≥ 0.9 log or if VA is less than 35 letters., (© 2020 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Visual acuity has been a significant outcome measure in clinical trials for patients suffering from neuro-ophthalmological diseases and multiple sclerosis; however, there are limited data on the comparison of various testing strategies in pediatric patients with these disorders. Clinical trials using vision as an outcome could include a variety of tools to assess the acuity, including 2-m and 4-m standardized retroilluminated charts., Methods: We investigated the difference in Early Treatment Diabetic Retinopathy Study (ETDRS) scores obtained using 2-m and 4-m charts, as well as the impact of optic neuritis, use of vision correction, age, and gender on visual acuity data from 71 patients with pediatric neuroimmunological conditions in a cross-sectional study., Results: We determine that the ETDRS letter scores obtained using 4-m charts are on average 3.43 points less (P = 0.0034) when testing monocular ETDRS letter scores and on average 4.14 points less (P = 0.0008) when testing binocular ETDRS letter scores, relative to that obtained using the 2-m charts. However, we find that when performing monocular testing, optic neuritis in the eye being tested did not result in a statistically significant difference between 2-m and 4-m ETDRS letter scores., Conclusions: Although visual acuity charts are formatted by the distance, there are significant differences in the number of letters correctly identified between 2-m and 4-m charts. Although the differences may not impact the clinical acuity, research protocols should consider these differences before collapsing data across disparate studies., Competing Interests: P. V. Sguigna has received grant support from the NMSS and PSTP. Morgan McCreary has nothing to declare. A. T. Waldman has received grant support from the NIH (K23NS069806), NMSS, and the United Leukodystrophy Foundation. She has received additional support for investigator-initiated research from Biogen Idec and Ionis Pharmaceuticals. She has received honoraria from UpToDate and consulting fees from Optum Inc. B. M. Greenberg has received grant support from the NIH, NMSS, Transverse Myelitis Association, PCORI, Guthy-Jackson Charitable Foundation, Chugai, MedImmune, MedDay, and Genentech. He has received consulting fees from Alexion, Novartis, EMD Serono, and Celgene. He is an unpaid board member of the Transverse Myelitis Association. The remaining authors report no conflicts of interest., (Copyright © 2020 by North American Neuro-Ophthalmology Society.)

Purpose: To investigate the clinical and histopathological features of congenital fibrovascular pupillary membrane (CFPM) in Chinese patients., Methods: This retrospective study reviewed CFPM cases treated at Beijing Children's Hospital. The clinical manifestations, approaches of treatment, outcomes, and histopathological findings were collected and analyzed., Results: A total of 33 patients with CFPM were reviewed. All patients had unilateral eye involvement. A total of 21 eyes (63.64%) had a white membrane that partially covered the pupil and 12 eyes (36.36%) had a membrane that completely covered the pupil. Of the 12 eyes with a complete pupillary membrane, 6 (50%) had glaucoma. For eyes with a partial pupillary membrane, 11 eyes (52.38%) were followed up at the outpatient clinic without surgery and 10 eyes (47.62%) underwent membranectomy and pupilloplasty due to visual axis blockage. For the 12 eyes with a complete pupillary membrane, 6 eyes (50%) with normal intraocular pressure (IOP) received membranectomy and pupilloplasty combined with iridectomy, and 1 (16.67%) of these 6 eyes underwent a reoperation after 5 months due to a recurrent membrane. Furthermore, 6 eyes (50%) with glaucoma had membranectomy, pupilloplasty, iridectomy, and goniosynechialysis. Among these 6 eyes, 2 eyes (33.33%) underwent a reoperation due to the recurrence of a membrane and 4 eyes (66.67%) had a pale optic disc. The histopathological findings revealed that these membranes were mainly composed of fibrous tissue, lymphocytes, pigment epithelial cells, and vascular tissues., Conclusions: CFPM has diverse manifestations, including a partial pupillary membrane, a complete pupillary membrane with normal IOP, and a complete pupillary membrane with glaucoma. Timely diagnosis and treatment are critical when the visual axis is blocked and/or the IOP is high. [ J Pediatr Ophthalmol Strabismus . 2021;58(2):105-111.] .

Abstract: A 42-year-old Algerian man presented for binocular oblique diplopia, hypersomnolence with drop attacks, bilateral hearing loss, and thoracic pain. He had a right thalamomesencephalic hemorrhage due to an underlying cavernous malformation treated with subtotal surgical resection. On neuro-ophthalmic examination, the patient had a left relative afferent pupillary defect and a right oculosympathetic efferent pupillary defect (i.e., Horner syndrome) in addition to other thalamomesencephalic eye and neurologic signs (right fourth nerve palsy, hearing loss, hemiparesis, and thalamic pain). Clinicians should recognize the localizing value of this unique constellation of mesencephalic afferent and efferent pupillary defects., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by North American Neuro-Ophthalmology Society.)

Objective: Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in young adults. Automated infrared pupillometry (AIP) has shown promising results in predicting neural damage in aneurysmal subarachnoid hemorrhage and ischemic stroke. We aimed to explore potential uses of AIP in triaging patients with TBI. We hypothesized that a brain injury severe enough to require an intervention would show Neurologic Pupil Index (NPI) changes., Methods: We conducted a prospective pilot study at a level-1 trauma center between November 2019 and February 2020. AIP readings of consecutive patients seen in the emergency department with blunt TBI and abnormal imaging findings on computed tomography were recorded by the assessing neurosurgery resident. The relationship between NPI and surgical intervention was studied., Results: Thirty-six patients were enrolled, 9 of whom received an intervention. NPI was dichotomized into normal (≥3) versus abnormal (<3) and was predictive of intervention (Fisher exact test; P < 0.0001). Six of the 9 patients had a Glasgow Coma Scale (GCS) score ≤8 and imaging signs of increased intracranial pressure (ICP) and underwent craniectomy (n = 4) or ICP monitor placement (n = 2) and had an abnormal NPI. Three patients underwent ICP monitor placement for GCS score ≤8 in accordance with TBI guidelines despite minimal imaging findings and had a normal NPI. The GCS score of these patients improved within 24 hours, requiring ICP monitor removal. NPI was normal in all patients who did not require intervention., Conclusions: AIP could be useful in triaging comatose patients after blunt TBI. An NPI ≥3 may be reassuring in patients with no signs of mass effect or increased ICP., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A 67-year-old woman presented with acute loss of vision to no light perception (NLP), a right afferent pupillary defect, and anisocoria with a nonreactive and dilated pupil in the right eye. Fundus examination showed pallid optic disc edema and a central retinal artery occlusion (CRAO) in the right eye. A temporal artery biopsy showed giant cell arteritis (GCA). Orbital involvement in GCA has been reported previously. However the combination of an afferent and efferent pupillary defect, NLP vision, pallid disc edema, and a CRAO in an elderly patient is likely a unique clinical combination that should strongly suggest GCA. Clinicians should be aware of the myriad presentations of GCA, including orbital ischemia.

Myelinated retinal nerve fiber layer is a benign retinal condition that is usually an incidental finding in a healthy patient. Visual acuity is typically not compromised, but some cases have other associated ocular conditions that can affect vision. Diagnosis in challenging atypical cases requires imaging studies to rule out other pathologies. The authors describe the case of a 2-year-old girl who presented with atypical optic nerve fiber myelination. [J Pediatr Ophthalmol Strabismus. 2020;57:e56-e58.]., (Copyright 2020, SLACK Incorporated.)

Purpose: The photopic negative response (PhNR) is a negative wave following the b-wave of the photopic electroretinogram (ERG). The PhNR originates from the retinal ganglion cells (RGCs), and it can be used to assess the function of RGCs noninvasively and objectively. The purpose of this study was to determine whether the relative amplitudes (affected/normal eye) of the PhNR are significantly correlated with the degree of the relative afferent pupillary defect (RAPD) in eyes with unilateral or asymmetrical damage of the optic nerve., Methods: The PhNRs of the full-field photopic ERGs were measured. In addition, videopupillography and automated perimetry were performed on 27 cases with asymmetrical optic nerve disorders including glaucoma. The differences of these assessments were expressed by the relative amplitudes of the PhNRs of the two eyes, the neutral density (ND) filter required to equate the amplitudes of the pupillary light reflexes between the two eyes, and differences of the mean defects (ΔMDs) of the sensitivities of the Humphrey visual fields. The correlations between these values were determined by linear regression analyses., Results: The relative PhNR amplitudes were significantly and negatively correlated with the ΔMDs (R 2  = 0.58, P = 0.0001). In addition, the relative PhNR amplitudes were moderately but significantly and positively correlated with the RAPDs (R 2  = 0.36, P = 0.002)., Conclusion: The relative amplitudes of the PhNR of the affected eyes to the contralateral eyes indicate an asymmetric alteration of the RGCs, and they can be used to monitor the physiology of the RGCs objectively.

Competing Interests: Competing interests: None declared.

Pierson syndrome is characterized by congenital nephrotic syndrome and bilateral microcoria. Genetically, mutations in the LAMB2 gene, which encodes the laminin β2 chain, lead to this disorder. To date, 98 cases and 50 different mutations have been reported in literature. There are no specific therapies for Pierson syndrome and treatment is supportive. The prognosis is poor because of progressive impairment of renal function and complications of renal failure. We report a novel homozygous mutation (c.1890G>T, p.Q630H) in the LAMB2 gene in a patient with Pierson syndrome who had atypical phenotypic feature such as epidermolysis bullosa., Competing Interests: None, (Sociedad Argentina de Pediatría.)

Competing Interests: None

Purpose: To determine the test-retest reliability and diagnostic accuracy of a binocular optical coherence tomography (OCT) prototype (Envision Diagnostics, El Segundo, California, USA) for pupillometry., Design: Assessment of diagnostic reliability and accuracy., Methods: Fifty participants with relative afferent pupillary defects (RAPDs) confirmed using the swinging flashlight method (mean age 49.6 years) and 50 healthy control subjects (mean age 31.3 years) were examined. Participants twice underwent an automated pupillometry examination using a binocular OCT system that presents a stimulus and simultaneously captures OCT images of the iris-pupil plane of both eyes. Participants underwent a single examination on the RAPDx (Konan Medical, Irvine, California, USA), an automated infrared pupillometer. Pupil parameters including maximum and minimum diameter, and anisocoria were measured. The magnitude of RAPD was calculated using the log of the ratio of the constriction amplitude between the eyes. A pathological RAPD was above ±0.5 log units on both devices., Results: The intraclass correlation coefficient was >0.90 for OCT-derived maximum pupil diameter, minimum pupil diameter, and anisocoria. The RAPDx had a sensitivity of 82% and a specificity of 94% for detection of RAPD whereas the binocular OCT had a sensitivity of 74% and specificity of 86%. The diagnostic accuracy of the RAPDx and binocular OCT was 88% (95% confidence interval 80%-94%) and 80% (95% confidence interval 71%-87%) respectively., Conclusions: Binocular OCT-derived pupil parameters had excellent test-retest reliability. The diagnostic accuracy of RAPD was inferior to the RAPDx and is likely related to factors such as eye movement during OCT capture. As OCT becomes ubiquitous, OCT-derived measurements may provide an efficient method of objectively quantifying the pupil responses., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2020. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2020. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.

Objectives: To test the feasibility of adding driving simulation tasks to measure visuospatial ability and processing speed to an existing neurocognitive battery for breast cancer survivors (BCSs)., Sample & Setting: 38 BCSs and 17 healthy controls from a cross-sectional pilot study conducted at the University of Kansas Medical Center., Methods & Variables: Exploratory substudy measuring pupillary response, visuospatial ability, and processing speed during two 10-minute driving simulations (with or without n-back testing) in a sample of BCSs with self-reported cognitive complaints and healthy controls., Results: Feasibility of measurement of pupillary response during driving simulation was demonstrated. No between-group differences were noted for pupillary response during driving simulation. BCSs had greater visuospatial ability and processing speed performance difficulties than healthy controls during driving simulation without n-back testing and slower n-back response time., Implications for Nursing: Preliminary evidence showed a possible link between cancer/treatment on visuospatial ability and processing speed in BCSs.