Automated vision screening of children using a mobile graphic device.

BACKGROUND/OBJECTIVE: Can measuring interocular brightness disparity, acuity, and colour vision classify children with amblyopia? SUBJECTS/METHODS: Two hundred eight subjects (3-14 years) were recruited for a prospective, observational protocol to measure interocular brightness disparity, uniocular acuities with and without a pinhole, and colour vision using an iPad. Subjects looked through polarizing filters and chose the brighter of two spaceships to measure interocular brightness disparity. The differential brightness of image pairs was varied through a staircase algorithm until equal brightness was perceived. Acuities and colour vision were tested with tumbling Es and AO-HRR colour plates, respectively. Unilateral amblyopia was later confirmed in two subjects. RESULTS: Binocular brightness balance on the iPad detected amblyopes with 100% sensitivity and specificity. Using 20/30 as cutoff for normal acuity, 1 of the amblyopes was detected, and non-amblyopes were excluded by visual acuity pinhole testing. The mean difference between iPad and E-Chart visual acuities with pinhole was 0.02 logMAR with limits of agreement from -0.08 to +0.11 logMAR. iPad and printed plates Colour vision testing produced identical results. Testing times were brief and exit pleasure responses were positive. Mean and range testing times for Brightness Sense, Colour vision, and Visual Acuity were 32.7 s (range = 12-63 s), 52.8 min (range = 17-95 s), and 88.75 s (range = 41-188 s), respectively. CONCLUSIONS: Interocular brightness disparity, acuity, and colour vision can be measured in children as young as 3 years old solely through playing a game on a mobile device. Interocular brightness disparity is a sensitive and specific method to detect unilateral amblyopia.

Failure of Goniosurgery for Glaucoma Associated With Sturge-Weber Syndrome.

PURPOSE: To report the surgical results of goniosurgery for children with glaucoma associated with Sturge-Weber syndrome. METHODS: Retrospective review of medical records of patients who had initial goniosurgery for glaucoma associated with Sturge-Weber syndrome. RESULTS: A total of 46 eyes of 42 patients who had glaucoma associated with Sturge-Weber syndrome and were treated with initial goniosurgery were identified to determine the efficacy of therapeutic goniotomy and trabeculotomy (goniosurgery). The average age at the time of goniosurgery was 1.5 years (range: 1 month to 23 years). Office intraocular pressure (IOP) measurements before goniosurgery were recorded in 76% of patients (32 of 42 patients) with an average measurement of 35 mm Hg (range: 25 to 50 mm Hg). The average interval to failure was 4 months (range: 1 to 48 months). Forty-six eyes underwent goniosurgery with a rate of failure of 98% (45 of 46 eyes) and a qualified success rate of 2% (1 of 46 eyes). Fifty-one goniotomy and 11 trabeculotomy procedures were performed. On gonioscopy, the filtration angles were all abnormal with variable width and visibility of the ciliary body band and less visible scleral spur. The trabecular meshwork was seen preoperatively in 100% of eyes (41 of 41 eyes) examined, all of which underwent goniosurgery. Five eyes underwent goniosurgery without documented gonioscopy. The ciliary body band was seen in 39% of eyes (16 of 41 eyes) and the scleral spur was visible in 10% of eyes (4 of 41 eyes). CONCLUSIONS: Goniosurgery is not an effective initial glaucoma surgery for glaucoma associated with Sturge-Weber syndrome. It can be used to temporize the IOP, but ultimately other forms of glaucoma surgery must be considered when indicated. [J Pediatr Ophthalmol Strabismus. 2020;57(6):384-387.].

Paroxysmal eye-head movements in Glut1 deficiency syndrome.

OBJECTIVE: To describe a characteristic paroxysmal eye-head movement disorder that occurs in infants with Glut1 deficiency syndrome (Glut1 DS). METHODS: We retrospectively reviewed the medical charts of 101 patients with Glut1 DS to obtain clinical data about episodic abnormal eye movements and analyzed video recordings of 18 eye movement episodes from 10 patients. RESULTS: A documented history of paroxysmal abnormal eye movements was found in 32/101 patients (32%), and a detailed description was available in 18 patients, presented here. Episodes started before age 6 months in 15/18 patients (83%), and preceded the onset of seizures in 10/16 patients (63%) who experienced both types of episodes. Eye movement episodes resolved, with or without treatment, by 6 years of age in 7/8 patients with documented long-term course. Episodes were brief (usually <5 minutes). Video analysis revealed that the eye movements were rapid, multidirectional, and often accompanied by a head movement in the same direction. Eye movements were separated by clear intervals of fixation, usually ranging from 200 to 800 ms. The movements were consistent with eye-head gaze saccades. These movements can be distinguished from opsoclonus by the presence of a clear intermovement fixation interval and the association of a same-direction head movement. CONCLUSIONS: Paroxysmal eye-head movements, for which we suggest the term aberrant gaze saccades, are an early symptom of Glut1 DS in infancy. Recognition of the episodes will facilitate prompt diagnosis of this treatable neurodevelopmental disorder.

Late-recognized primary congenital glaucoma.

PURPOSE: To describe a cohort of children with late-recognized primary congenital glaucoma (LRPCG), including age of presentation, age-related diagnostic signs, clinical abnormalities, and results of glaucoma surgery. METHODS: The medical records of 31 patients (49 eyes) with PCG recognized after 1 year of age were reviewed retrospectively. Patients were confirmed to have PCG based on their increased intraocular pressure (IOP), anterior segment abnormalities including findings on gonioscopy, and the absence of other causes of childhood glaucoma. The outcome of glaucoma surgery was reviewed and success measured by assessment of the relative control of IOP, occurrence of significant complications, and need for additional glaucoma surgery. RESULTS: Average age at diagnosis of glaucoma was 4.7 years (36% diagnosed at > 4 years of age). The most common initial diagnostic signs were corneal enlargement (46%, average age of 2.0 years), photophobia (20%, average age of 3.3 years), and suspected poor visual acuity (32%, average age of 9.9 years). Corneal cloudiness was not an initial sign for any patient. Haab's striae were present in 60% of the affected 49 eyes. Gonioscopy findings were abnormal in 82%, but the ciliary body band was seen in 81% and the scleral spur was visible in 47%. Sixty-one goniotomy procedures were performed for 39 eyes with overall success in 95% (37 eyes) and complete success in 65% (27 eyes). The final visual acuity was 20/200 or worse in 31% (15 eyes) and 20/40 or better in 60% (29 eyes). CONCLUSIONS: An awareness of and familiarity with the subtle diagnostic signs of LRPCG can enable its differentiation from primary juvenile glaucoma and contribute to earlier recognition and treatment. Glaucoma surgery is often required for LRPCG and goniosurgery is the recommended initial procedure.

Telemedical diagnosis of retinopathy of prematurity: accuracy of expert versus non-expert graders.

BACKGROUND/AIMS: To assess accuracy of telemedical retinopathy of prematurity (ROP) diagnosis by trained non-expert graders compared with expert graders. METHODS: Eye examinations (n=248) from 67 consecutive infants were captured using wide-angle retinal photography (RetCam-II, Clarity Medical Systems, Pleasanton, California, USA). Non-expert graders attended two 1-h training sessions on image-based ROP diagnosis. Using a web-based telemedicine system, 14 non-expert and three expert graders provided a diagnosis for each eye: no ROP, mild ROP, type 2 pre-threshold ROP or treatment-requiring ROP. All diagnoses were compared with a reference standard of dilated indirect ophthalmoscopy by an experienced paediatric ophthalmologist. RESULTS: For detection of type 2 or worse ROP, the mean (range) sensitivities and specificities were 0.95 (0.94-0.97) and 0.93 (0.91-0.96) for experts, 0.87 (0.71-0.97) and 0.73 (0.39-0.95) for resident non-experts, and 0.73 (0.41-0.88) and 0.91 (0.84-0.96) for student non-experts, respectively. For detection of treatment-requiring ROP, the mean (range) sensitivities and specificities were 1.00 (1.00-1.00) and 0.93 (0.88-0.96) for experts, 0.88 (0.50-1.00) and 0.84 (0.71-0.98) for resident non-experts, and 0.82 (0.42-1.00) and 0.92 (0.83-0.97) for student non-experts, respectively. CONCLUSIONS: Mean sensitivity and specificity of trained non-experts were lower than that of experts, although several non-experts had high accuracy. Development of methods for training non-expert graders may help support telemedical ROP evaluation.

Retinopathy of prematurity management using single-image vs multiple-image telemedicine examinations.

PURPOSE: To compare performance of single-image vs multiple-image telemedicine examinations for retinopathy of prematurity (ROP) diagnosis. DESIGN: Prospective comparative study. METHODS: A total of 248 eyes from 67 consecutive infants underwent wide-angle retinal imaging by a trained neonatal nurse at 31 to 33 weeks and/or 35 to 37 weeks postmenstrual age (PMA) at a single academic institution. Data were uploaded to a web-based telemedicine system and interpreted by three masked retinal specialists. Diagnoses were provided based on single images, and subsequently on multiple images, from both eyes of each infant. Findings were compared to a reference standard of indirect ophthalmoscopy by a pediatric ophthalmologist. Primary outcome measures were recommended follow-up interval, presence of plus disease, presence of type-2 or worse ROP, and presence of visible peripheral ROP. RESULTS: Among the three graders, mean sensitivity/specificity for detection of infants requiring follow-up in less than one week were 0.85/0.93 by single-image examination and 0.91/0.88 by multiple-image examination at 35 to 37 weeks PMA. Mean sensitivity/specificity for detection of infants with type-2 or worse ROP were 0.82/0.95 by single-image examination and 1.00/0.91 by multiple-image examination at 35 to 37 weeks PMA. Mean sensitivity/specificity for detection of plus disease were 1.00/0.86 by single-image examination and 1.00/0.87 by multiple-image examination at 35 to 37 weeks PMA. There were no statistically-significant intragrader differences between accuracy of single-image and multiple-image telemedicine examinations for detection of plus disease. CONCLUSIONS: Single-image and multiple-image telemedicine examinations perform comparably for determination of recommended follow-up interval and detection of plus disease. This may have implications for development of screening protocols, particularly in areas with limited access to ophthalmic care.

Telemedical diagnosis of retinopathy of prematurity intraphysician agreement between ophthalmoscopic examination and image-based interpretation.

OBJECTIVE: To evaluate the intraphysician agreement between ophthalmoscopic examination and image-based telemedical interpretation for retinopathy of prematurity (ROP) diagnosis, when performed by the same expert physician grader. DESIGN: Prospective, nonrandomized, comparative study. PARTICIPANTS: Sixty-seven consecutive premature infants who underwent ROP examination at a major university medical center whose parents consented for participation. METHODS: Infants underwent standard dilated ophthalmoscopy by one of two pediatric ophthalmologists, followed by retinal imaging with a commercially available wide-angle fundus camera by a trained neonatal nurse. Study examinations were performed at 31 to 33 weeks postmenstrual age (PMA) and/or 35 to 37 weeks PMA. Images were uploaded to a Web-based telemedicine system developed by the authors. After a 4- to 12-month period, telemedical interpretations were performed in which each physician graded images from infants upon whom he had initially performed ophthalmoscopic examinations. Diagnoses were classified using an ordinal scale: no ROP, mild ROP, type 2 prethreshold ROP, and treatment-requiring ROP. MAIN OUTCOME MEASURES: Absolute intraphysician agreement and kappa statistic between ophthalmoscopic examination and telemedical interpretation were calculated by eye. All intraphysician discrepancies were reviewed, and underlying causes were classified by eye as no ROP identified by ophthalmoscopic examination, no ROP identified by telemedical interpretation, discrepancy about presence of zone 1 ROP, discrepancy about presence of plus disease, or other discrepancy in classification of ROP stage. RESULTS: Absolute intraphysician agreement between ophthalmoscopic examination and telemedical interpretation was 86.3%. The kappa statistic for intraphysician agreement between examinations ranged from 0.657 (substantial agreement) for diagnosis of treatment-requiring ROP to 0.854 (near-perfect agreement) for diagnosis of mild or worse ROP. Among 206 eye examinations (103 infant examinations), there were 28 (13.6%) intraphysician discrepancies in diagnosis, 8 of which resulted from uncertainty about presence of zone 1 disease and 4 from uncertainty about presence of plus disease. CONCLUSIONS: Intraphysician agreement between ophthalmoscopic examination and telemedical interpretation for ROP was very high. Neither examination modality appeared to have a systematic tendency to overdiagnose or underdiagnose ROP. Diagnosis of zone 1 disease and plus disease were major sources of clinically significant discrepancies.

Telemedical retinopathy of prematurity diagnosis: accuracy, reliability, and image quality.

OBJECTIVE: To prospectively measure accuracy, reliability, and image quality of telemedical retinopathy of prematurity (ROP) diagnosis. METHODS: Two-hundred forty-eight eyes from 67 consecutive infants underwent wide-angle retinal imaging by a trained neonatal nurse at 31 to 33 weeks' and/or 35 to 37 weeks' postmenstrual age (PMA) using a standard protocol. Data were uploaded to a Web-based telemedicine system and interpreted by 3 expert retinal specialist graders who provided a diagnosis (no ROP, mild ROP, type 2 prethreshold ROP, treatment-requiring ROP) and an evaluation of image quality for each eye. Findings were compared with a reference standard of indirect ophthalmoscopy by an experienced pediatric ophthalmologist. RESULTS: At 35 to 37 weeks' PMA, sensitivity and specificity for diagnosis of mild or worse ROP were 0.908 and 1.000 for grader A, 0.971 and 1.000 for grader B, and 0.908 and 0.977 for grader C. Sensitivity and specificity for diagnosis of type 2 prethreshold or worse ROP were 1.000 and 0.943 for grader A, 1.000 and 0.930 for grader B, and 1.000 and 0.851 for grader C. At 35 to 37 weeks' PMA, weighted kappa for intergrader reliability was 0.791 to 0.889, and kappa for intragrader reliability for detection of type 2 prethreshold or worse ROP was 0.769 to 1.000. Image technical quality was rated as "adequate" or "possibly adequate" for diagnosis in 93.3% to 100% of eyes. CONCLUSION: A telemedicine system using nurse-captured retinal images has the potential to improve existing shortcomings of ROP management, particularly at later PMAs.

Sequential and distinct roles of the cadherin domain-containing protein Axl2p in cell polarization in yeast cell cycle.

Polarization of cell growth along a defined axis is essential for the generation of cell and tissue polarity. In the budding yeast Saccharomyces cerevisiae, Axl2p plays an essential role in polarity-axis determination, or more specifically, axial budding in MATa or alpha cells. Axl2p is a type I membrane glycoprotein containing four cadherin-like motifs in its extracellular domain. However, it is not known when and how Axl2p functions together with other components of the axial landmark, such as Bud3p and Bud4p, to direct axial budding. Here, we show that the recruitment of Axl2p to the bud neck after S/G2 phase of the cell cycle depends on Bud3p and Bud4p. This recruitment is mediated via an interaction between Bud4p and the central region of the Axl2p cytoplasmic tail. This region of Axl2p, together with its N-terminal region and its transmembrane domain, is sufficient for axial budding. In addition, our work demonstrates a previously unappreciated role for Axl2p. Axl2p interacts with Cdc42p and other polarity-establishment proteins, and it regulates septin organization in late G1 independently of its role in polarity-axis determination. Together, these results suggest that Axl2p plays sequential and distinct roles in the regulation of cellular morphogenesis in yeast cell cycle.

Is there a role for high-frequency ultrasonography in clinical staging of retinopathy of prematurity?

PURPOSE: To compare 20-MHz ultrasonography with ophthalmoscopy in the staging of retinopathy of prematurity (ROP). METHODS: We used a handheld 20-MHz ultrasound system to examine 38 eyes of 19 neonates who had an indirect ophthalmoscopic examination (diagnosis masked) within 48 hours prior to ultrasonography. Determination of ROP by indirect ophthalmoscopy was compared with independent identification of ultrasonic features indicative of ROP stages. RESULTS: In masked cases, ultrasonography correctly identified 13 of 18 (72.2% sensitivity) eyes with zone 2, stage 2 ROP or worse and 19 of 20 (95.0% specificity) normal eyes (zone 2, stage 1 ROP or better) (chi-square, 18.4; P < .001). CONCLUSION: In the neonatal nursery, a 20-MHz handheld ultrasound system may be an effective screening tool to initially identify ROP for further ophthalmoscopic evaluation and management.

Cobalamin C disease presenting as hemolytic-uremic syndrome in the neonatal period.

Anew case of cobalamin C disease associated with hemolytic-uremic syndrome (HUS) in the neonatal period is described. A 28-day-old boy presented with failure to thrive, hypotonia, pancytopenia, and features of HUS (microangiopathic hemolytic anemia, thrombocytopenia, and renal failure). The possibility of the diagnosis of an underlying vitamin B12 disorder was prompted by evidence of megaloblastic changes on the peripheral smear and by finding in the literature a suggested association of neonatal HUS with this cobalamin-related metabolic disorder. Amino acid analysis showed elevated homocysteine levels in the plasma and increased levels of both homocysteine and methyl malonic acid in the urine. Diagnosis of cobalamin C disease was confirmed by complementation studies using skin fibroblasts. Therapy included parenteral hydroxocobalamin, carnitine, and leucovorin calcium (folinic acid). Cobalamin C disease should be considered in the diagnosis of patients presenting with HUS in infancy who have unexplained megaloblastosis, pancytopenia, neurologic impairment, and failure to thrive. Early diagnosis and institution of therapy may be effective in improving survival and quality of life.