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Purpose The purpose of this study was to examine the expression of glial derived neurotrophic factor (GDNF), the GDNF receptors GFRα1 and GFRα2, ciliary neurotrophic factor (CNTF), and the CNTF receptor CNTFRα in normal and glaucomatous human tissue. Methods Human retinas were collected from 8 donors that had been clinically diagnosed and treated for glaucoma, and also from 9 healthy control donors. Immunohistochemical analysis for each trophic factor and receptor was performed. The percent of each retinal section labeled with each antibody was quantified for the total retinal thickness, and separately for the retinal ganglion cell (RGC) complex + retinal nerve fiber layer (RNFL). The expression of each protein was correlated with measures of the subject's ocular histories. Results The percentage area immunopositive for GFRα2 was significantly decreased in the total retinal thickness containing all retinal layers and in the combined RGC complex + RNFL in glaucomatous eyes in both the peripapillary region and more peripheral retinal locations. We also observed a decrease in GFRα1 expression in the peripapillary RGC Complex + RNFL in glaucoma patients compared to healthy control patients. We also observed a relationship between GDNF and its receptors with several outcomes obtained from the medical record. No differences in CNTF or CNTFR labeling were observed. Conclusion Decreases in GDNF receptor expression in glaucomatous tissue may limit the potential for neuroprotective therapy by supplementation with GDNF.

The human choroid is a heterogeneous, highly vascular connective tissue that dysfunctions in age-related macular degeneration (AMD). In this study, we performed single-cell RNA sequencing on 21 human choroids, 11 of which were derived from donors with early atrophic or neovascular AMD. Using this large donor cohort, we identified new gene expression signatures and immunohistochemically characterized discrete populations of resident macrophages, monocytes/inflammatory macrophages and dendritic cells. These three immune populations demonstrated unique expression patterns for AMD genetic risk factors, with dendritic cells possessing the highest expression of the neovascular AMD-associated MMP9 gene. Additionally, we performed trajectory analysis to model transcriptomic changes across the choroidal vasculature, and we identified expression signatures for endothelial cells from choroidal arterioles and venules. Finally, we performed differential expression analysis between control, early atrophic AMD, and neovascular AMD samples, and we observed that early atrophic AMD samples had high expression of SPARCL1, a gene that has been shown to increase in response to endothelial damage. Likewise, neovascular endothelial cells harbored gene expression changes consistent with endothelial cell damage and demonstrated increased expression of the sialomucins CD34 and ENCM, which were also observed at the protein level within neovascular membranes. Overall, this study characterizes the molecular features of new populations of choroidal endothelial cells and mononuclear phagocytes in a large cohort of AMD and control human donors.

Objective: The development of ciliochoroidal effusions and secondary acute angle-closure crisis (AACC) is an uncommon side effect of topiramate, a common antiepileptic now FDA-approved for migraine prophylaxis. The mechanisms that underlie the development of ciliochoroidal effusions after topiramate use remain unclear. Materials and Methods: Ultrasound biomicroscopy (UBM) was also performed in all participants after stopping topiramate. Results: Six patient cases are presented with medication-induced AACC following the initiation or escalation of topiramate. Ciliochoroidal effusions were confirmed by gray-scale sonography in all patients at presentation. The images revealed either plateau iris configuration or atypical plateau iris configuration. Plateau iris configuration is defined by presence of an anteriorly rotated ciliary body processes and an absent posterior sulcus. Atypical plateau iris configuration refers to when the iris inserts directly into the ciliary body face. This case series, of medication-induced angle-closure crisis, suggests that plateau iris configuration is a shared anatomical feature in the development of topiramate-induced ciliochoroidal effusions.

The standardization of variant curation criteria is essential for accurate interpretation of genetic results and clinical care of patients. The variant curation guidelines developed by the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) in 2015 are widely used but are not gene specific. To address this issue, the Clinical Genome Resource (ClinGen) Variant Curation Expert Panels (VCEP) have been tasked with developing gene-specific variant curation guidelines. The Glaucoma VCEP was created to develop rule specifications for genes associated with primary glaucoma, including myocilin (MYOC), the most common cause of Mendelian glaucoma. Of the 28 ACMG/AMP criteria, the Glaucoma VCEP adapted 15 rules to MYOC, and deemed 13 rules not applicable. Key specifications included determining minor allele frequency thresholds, developing an approach to counting probands and segregations, and reviewed functional assays. The rules were piloted on 81 variants and led to a change in classification in 38% of those that were classified in ClinVar with functional evidence influencing the classification of 18 variants. The standardized variant curation guidelines for MYOC provide a framework for the consistent application of the rules between laboratories, to improve MYOC genetic testing in the management of glaucoma.

To examine the expression of brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, tropomyosin-related kinase receptor-B (TrkB), in normal and glaucomatous human retinas.Human retinas were collected from 8 donors who had been clinically diagnosed and treated for glaucoma, and from 9 control donors. Immunohistochemical analysis for BDNF and TrkB was performed. The percent of each retina expressing BDNF and TrkB was quantified for the total retinal thickness, and separately for the retinal ganglion cell (RGC) complex + retinal nerve fiber layer (RNFL). The expression of each protein was correlated with clinical outcomes obtained from the subject's ocular histories.There was no significant difference in BDNF or TrkB expression when comparing glaucomatous and control retinas. Correlation analysis revealed a significant relationship between BDNF expression and the use of prostaglandin analogs. TrkB expression was highly correlated with the last-measured intraocular pressure (IOP), the use of carbonic anhydrase inhibitors, the use of beta blockers, and the total number of drugs used for the treatment of glaucoma.Topical drugs used to treat glaucoma were associated with an increase in retinal BDNF and TrkB expression in human retina, independent of IOP, which may represent molecular evidence of neuroprotective pathway activation.

Background Glaucoma is a leading cause of visual disability and blindness. Release of iris pigment within the eye, pigment dispersion syndrome (PDS), can lead to one type of glaucoma known as pigmentary glaucoma. PDS has a genetic component, however, the genes involved with this condition are largely unknown. We sought to discover genes that cause PDS by testing cohorts of patients and controls for mutations using a tiered analysis of exome data. Results Our primary analysis evaluated melanosome-related genes that cause dispersion of iris pigment in mice (TYRP1, GPNMB, LYST, DCT, and MITF). We identified rare mutations, but they were not statistically enriched in PDS patients. Our secondary analyses examined PMEL (previously linked with PDS), MRAP, and 19 other genes. Four MRAP mutations were identified in PDS cases but not in controls (p = 0.016). Immunohistochemical analysis of human donor eyes revealed abundant MRAP protein in the iris, the source of pigment in PDS. However, analysis of MRAP in additional cohorts (415 cases and 1645 controls) did not support an association with PDS. We also did not confirm a link between PMEL and PDS in our cohorts due to lack of reported mutations and similar frequency of the variants in PDS patients as in control subjects. Conclusions We did not detect a statistical enrichment of mutations in melanosome-related genes in human PDS patients and we found conflicting data about the likely pathogenicity of MRAP mutations. PDS may have a complex genetic basis that is not easily unraveled with exome analyses.

Purpose: Aniridia is a rare congenital eye disease, characterized by a constellation of symptoms including hypoplastic irides, foveal hypoplasia, early cataract, corneal stem cell deficienc...

Early age-related macular degeneration (AMD) is characterized by degeneration of the choriocapillaris, the vascular supply of retinal photoreceptor cells. We assessed vascular loss during disease progression in the choriocapillaris and larger vessels in the deeper choroid. Human donor maculae from controls (n = 99), early AMD (n = 35), or clinically diagnosed with geographic atrophy (GA; n = 9, collected from outside the zone of retinal pigment epithelium degeneration) were evaluated using Ulex europaeus agglutinin-I labeling to discriminate between vessels with intact endothelial cells and ghost vessels. Morphometric analyses of choriocapillaris density (cross-sectional area of capillary lumens divided by length) and of vascular lumen/stroma ratio in the outer choroid were performed. Choriocapillaris loss was observed in early AMD (Bonferroni-corrected P = 0.024) with greater loss in GA (Bonferroni-corrected P < 10(−9)), even in areas of intact retinal pigment epithelium. In contrast, changes in lumen/stroma ratio in the outer choroid were not found to differ between controls and AMD or GA eyes (P > 0.05), suggesting choriocapillaris changes are more prevalent in AMD than those in the outer choroid. In addition, vascular endothelial growth factor-A levels were negatively correlated with choriocapillaris vascular density. These findings support the concept that choroidal vascular degeneration, predominantly in the microvasculature, contributes to dry AMD progression. Addressing capillary loss in AMD remains an important translational target.

Background Nanophthalmos has a significant genetic background and disease-causing mutations have been recently been reported in the myelin regulatory factor (MYRF) gene. We report clinical features in a patient with nanophthalmos and a Thr518Met MYRF mutation. Case presentation A three-year-old male was discovered to have nanophthalmos after first presenting to the emergency department for a frontal headache, eye pain, emesis, and lethargy. Imaging studies (CT and MRI) were negative except for increased posterior fossa cerebrospinal fluid. Subsequent examinations revealed nanophthalmos (short axial eye lengths 18.1 mm OD and 18.3 mm OS), microcornea, and a large crystalline lens. Peripheral chorioretinal pigment abnormalities were also observed. He experienced episodes of marked ocular hypertension (53 mmHg OD and 60 mmHg) likely due to intermittent angle closure precipitated by nanophthalmos. The ocular hypertension was responsive to topical medicines. Genetic analysis of known nanophthalmos genes MFRP and TMEM98 were negative, while a novel mutation, Thr518Met was detected in MYRF. The Thr518Met mutation was absent from 362 matched normal controls and was extremely rare in a large population database, allele frequency of 0.000024. The Thr518Met mutation altered a highly conserved amino acid in the MYRF protein and three of four algorithms suggested that this mutation is likely pathogenic. Finally, molecular modeling showed that the Thr518Met mutation is damaging to MYRF structure. Together these data suggest that the Thr518Met mutation causes nanophthalmos. Conclusions Nanophthalmos may present at an early age with features of angle closure glaucoma and a Thr518Met mutation in MYRF was detected in a patient with nanophthalmos. Prevalence data, homology data, mutation analysis data, and protein modeling data suggest that this variant is pathogenic and may expand the phenotypic range of syndromic nanophthalmos caused by MYRF mutations to include central nervous system abnormalities (increased posterior fossa cerebrospinal fluid).

An 88-year-old woman with a history of recent complicated pacemaker insertion presented with acute-onset malignant glaucoma recalcitrant to conservative medical therapy. Surgical intervention was discussed; however, given her complex cardiac history and recent postoperative state, the risk of anesthesia-related systemic adverse events was deemed unacceptably high. As such, a slit-lamp procedure was recommended to break the attack of malignant glaucoma. Here within, we report a novel technique of breaking an attack of malignant glaucoma by needling the anterior hyaloid face at the slit lamp. With this technique, a 25-G needle was entered through the pars plana and was advanced through the anterior hyaloid face, zonules, and peripheral iridotomy to create a unicameral eye and successfully break the malignant closure attack.

Purpose To report a case of spontaneous dislocation of a gelatin microstent 6 months after the initial uncomplicated surgery. Patients and methods We describe a 73-year-old man with a history of advanced primary open-angle glaucoma who had previously undergone an unsuccessful micropulse transcleral cyclophotocoagulation of the left eye. He underwent an uncomplicated combined phacoemulsification with an ab interno gelatin microstent, but was noted to have a spontaneous dislocation of the microstent 6 months postoperatively. Results His postoperative course was largely unremarkable. He underwent a total of 5 bleb needlings, 1 immediately postoperatively because of intra-Tenon's positioning of the microstent. At his 6-month follow-up, he had a needling with both 5-flurouracil and subconjunctival bevacizumab. Despite postprocedural gonioscopy confirmation of the microstent positioning, the patient returned 1 week later with a fully dislocated microstent. The dislocation was asymptomatic, and his intraocular pressure remained in the single digits. Conclusions The ab interno gelatin microstent is a promising new procedure, but presents unique challenges. As the procedure is still new, more complications are expected to come to light. Although gelatin microstent migration and dislocation appears to be rare, it is important to recognize this postoperative complication. To our knowledge, this is the first report of a spontaneous dislocation of the gelatin microstent without a clear inciting event. This case reiterates the importance of continued follow-up of these cases, and will hopefully help begin to shed light on preoperative considerations and patient selection.

Precis Gonioscopy-assisted transluminal trabeculotomy (GATT) is a novel technique that lowers intraocular pressure (IOP) by fracturing the trabecular meshwork. In this retrospective chart review, GATT was found to be effective at lowering the intraocular pressure for steroid-induced glaucoma (SIG). Purpose GATT is a novel microinvasive glaucoma surgery that builds on traditional trabeculotomy techniques to decrease the proximal resistance of conventional outflow, and it is proposed to be an effective surgical treatment for SIG. The purpose of this study is to evaluate the efficacy of GATT for lowering the IOP in SIG. Methods and patients A retrospective chart review was performed of all GATT procedures performed on patients with a predominant diagnosis of steroid-induced glaucoma between March 1, 2016 and March 30,2018 at the University of Michigan. Primary outcome measures include IOP, the number of IOP-lowering medications prescribed, and the topical steroid dosing over the duration of follow-up. Results A total of 13 patients with steroid-induced glaucoma underwent the GATT procedure. There was a significant reduction in the mean IOP at all postoperative visits. The average IOP decreased by 16.4 (55%) to 19.5 mm Hg (63%) between 3 and 24 months postoperatively. By 24 months, all patients had a reduction in IOP of >20%. The number of glaucoma medications also decreased significantly from an average of 3.1 medications preoperatively to an average of 0.8 medications at last follow-up. The majority of patients (>67%) required continued use of steroids at all postoperative visits. The most common postoperative complication was a transient hyphema (38%). No patients required a repeat glaucoma surgery or anterior chamber washout. Conclusions This small case series suggests that GATT is an effective and safe surgical technique to decrease IOP and decrease medication burden in patients with predominantly steroid-induced glaucoma. To our knowledge, this is the first study looking specifically at the efficacy of GATT for predominantly SIG.

Importance For research involving big data, researchers must accurately identify patients with ocular diseases or phenotypes of interest. Reliance on administrative billing codes alone for this purpose is limiting. Objective To develop a method to accurately identify the presence or absence of ocular conditions of interest using electronic health record (EHR) data. Design, Setting, and Participants This study is a retrospective analysis of the EHR data of patients (n = 122 339) in the Sight Outcomes Research Collaborative Ophthalmology Data Repository who received eye care at participating academic medical centers between August 1, 2012, and August 31, 2017. An algorithm that searches structured and unstructured (free-text) EHR data for conditions of interest was developed and then tested to determine how well it could detect the presence or absence of exfoliation syndrome (XFS). The algorithm was trained to search for evidence of XFS among a sample of patients with and without XFS (n = 200) by reviewingInternational Classification of Diseases, Ninth RevisionorInternational Statistical Classification of Diseases and Related Health Problems, Tenth Revision(ICD-9orICD-10) billing codes, the patient’s problem list, and text within the ocular examination section and unstructured (free-text) data in the EHR. The likelihood that each patient had XFS was estimated using logistic least absolute shrinkage and selection operator (LASSO) regression. The EHR data of all patients were run through the algorithm to generate an XFS probability score for each patient. The algorithm was validated with review of EHRs by glaucoma specialists. Main Outcomes and Measures Positive predictive value (PPV) and negative predictive value (NPV) of the algorithm were computed as the proportion of patients correctly classified with XFS or without XFS. Results This study included 122 339 patients, with a mean (SD) age of 52.4 (25.1) years. Of these patients, 69 002 (56.4%) were female and 99 579 (81.4%) were white. The algorithm assigned a less than 10% probability of XFS for 121 085 patients (99.0%) as well as an XFS probability score of more than 75% for 543 patients (0.4%), more than 90% for 353 patients (0.3%), and more than 99% for 83 patients (0.07%). Validated by glaucoma specialists, the algorithm had a PPV of 95.0% (95% CI, 89.5%-97.7%) and an NPV of 100% (95% CI, 91.2%-100%). When there wasICD-9orICD-10billing code documentation of XFS, in 86% or 96% of the records, respectively, evidence of XFS was also recorded elsewhere in the EHR. Conversely, when there was clinical examination or free-text evidence of XFS, it was documented withICD-9codes only approximately 40% of the time and even less often withICD-10codes. Conclusions and Relevance The algorithm developed, tested, and validated in this study appears to be better at identifying the presence or absence of XFS in EHR data than the conventional approach of assessing only billing codes; such an algorithm may enhance the ability of investigators to use EHR data to study patients with ocular diseases.

PURPOSE: To determine the rate of visual recovery following hyphema caused by traumatic blunt force injury in children. METHODS: The medical records of patients evaluated between July 2008 and July 2014 were reviewed retrospectively. Primary outcome measures included presenting and follow-up visual acuities. RESULTS: At total of 56 eyes of 55 children (

Objective To develop and institute a standardized ophthalmology-specific operating room checklist, and to test adherence to the surgical checklist components after implementation. Design An ophthalmology-specific operative room checklist was developed using recommendations from surgical preoperative checklists from other subspecialties and checklists specific to cataract surgery. This standardized checklist was then implemented into the operating rooms. Operative room staff was trained on its use. Adherence to the checklist was measured prospectively. Setting Surgical centers at Kellogg Eye Center in Ann Arbor and Livonia, Michigan. Participants Patients undergoing ophthalmic surgery at the Livonia and Ann Arbor surgical centers. Main Outcome(s) and Measure(s) The primary outcome measures were surgical team adherence to each category of the operative checklist (preop, prebrief, preanesthesia verification, time-out, intraocular lens measurement/confirmation for cataract cases, debrief). Adherence to the subsections of the operative checklist was measured during three periods over the course of 1 year: baseline, postintervention (after introduction of the checklist in all operating rooms), and postadjustment (after additional training was provided to operating room staff and incentives to collect data were provided to personnel responsible for collecting it). Results A total of 2,532 surgical cases were included in the analysis. Baseline adherence ranged from 87 to 90% across preop, prebrief, preanesthesia, and time-out verification sections of the operative checklist. After the institution of the intervention and adjustments, adherence to the surgical checklist improved significantly across all areas of the checklist to 97–98% (p Conclusions and Relevance The development and implementation of an ophthalmology-specific operative room checklist increase adherence to recommended safety checks prior to the start of surgery. To maximize patient safety, the same or similar checklist is recommended for use in all ophthalmology operating rooms.

Mutations in each of three genes, myocilin (MYOC), optineurin (OPTN), and TANK binding kinase 1 (TBK1), may cause primary open-angle glaucoma (POAG) that is inherited as a Mendelian trait. MYOC mutations cause 3–4% of POAG cases with IOP >21 mmHg, while mutations in OPTN, TBK1, and MYOC each cause ∼1% of POAG with IOP ≤21 mmHg, i.e. normal tension glaucoma. Identification of these disease-causing genes has provided insights into glaucoma pathogenesis. Mutations in MYOC cause a cascade of abnormalities in the trabecular meshwork including intracellular retention of MYOC protein, decreased aqueous outflow, higher intraocular pressure, and glaucoma. Investigation of MYOC mutations demonstrated that abnormal retention of intracellular MYOC and stimulation of endoplasmic reticular (ER) stress may be important steps in the development of MYOC-associated glaucoma. Mutations in OPTN and TBK1 cause a dysregulation of autophagy which may directly cause retinal ganglion cell damage and normal tension glaucoma. Discovery of these Mendelian causes of glaucoma has also provided a new set of potential therapeutic targets that may ultimately lead to novel, gene-directed glaucoma treatments.

Neuroendocrine tumors (NETs) are rare neoplasms whose incidence has increased five-fold over the past three decades1. These tumors are derived from enterochromaffin and islet cells, and may secrete a variety of polypeptides, which may cause symptoms and can be useful for diagnosis, detection, and treatment of these tumors2. Two of the most common sites of these malignancies involving the digestive system are the small bowel (SBNETs) and pancreas (PNETs), and approximately 58% of patients with SBNETs and 72% of those with PNETs present with metastatic disease3, primarily to the liver. It has been estimated that as many as 10–20% of patients with liver metastases present with an unknown primary site4, and in these cases, being able to determine the primary site has important implications for surgical approach and therapeutic measures. The preferred treatment for SBNETs and PNETs is surgical resection, even in the face of metastatic disease5. Medical therapy for metastatic NETs includes the use of somatostatin analogs, which helps to control hormonal symptoms as well as improve time to progression6. Sandostatin is an 8 amino acid analog of somatostatin which mediates its effects by binding to the type 2 somatostatin receptor (SSTR2, a G-protein coupled receptor [GPCR]) on the cell surface of NETs. Sandostatin has also been useful in localization of tumors when labeled with Indium, but its success in locating primary GI sites of NETs in patients presenting with liver metastases has been limited4. Chemotherapy has also had limited response rates in NETs, with improved survival rates in those with pancreatic tumor sites. Treatment of pancreatic NETs (PNETs) has included combinations of streptozotocin and 5-fluorouracil and/or doxorubicin, with response rates of approximately 40%7. However, in non-pancreatic NETs, the response rate is only 25%7. More recently, Sunitinib and Everolimus have been demonstrated to lead to improved disease free survival for patients with advanced PNETs8, 9. Even patients with advanced disease may have prolonged survival, with median survivals of 56 and 24 months in metastatic SBNETs and PNETs, respectively1. These statistics could potentially be further improved by uncovering new targets, such as additional cell surface receptors (besides SSTR2) which could be exploited for diagnosis, imaging, and therapy. Further understanding of these NETs could come from analysis of their expression patterns, which might then be used to categorize the genetic profiles of different primary sites. This would hold promise for determining the site of origin from biopsies of liver metastases, and to identify targets for future therapy. To date, the limited gene expression studies performed in SBNETs and PNETs have not identified consistent and useful patterns of over and underexpressed genes10–14, and therefore the objective of this study was to examine matched tumor and normal tissues from these sites, then determine whether these could be used to predict the primary sites from liver metastases.

To assess long-term effects of genotype on chorioretinopathy severity in patients with mitochondrial trifunctional protein (MTP) disorders.Retrospective case series.Consecutive patients with MTP disorders evaluated at a single center from 1994 through 2015, including 18 patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and 3 patients with trifunctional protein deficiency (TFPD).Local records from all visits were reviewed. Every participant underwent a complete ophthalmic examination and was evaluated by a metabolic physician and dietitian. Nine patients underwent ancillary funduscopic imaging including optical coherence tomography (OCT) and OCT angiography.The primary outcome measure was best-corrected visual acuity at the final visit. Secondary outcome measures included spherical equivalent refraction, visual fields, electroretinography B-wave amplitudes, and qualitative imaging findings.Participants were followed up for a median of 5.6 years (range 0.3-20.2 years). The median age of LCHADD participants at initial and final visits was 2.3 and 11.9 years, whereas that for TFPD participants at initial and final visits was 4.7 and 15.5 years, respectively. Four long-term survivors older than 16 years were included (3 with LCHADD and 1 with TFPD). The LCHADD participants demonstrated a steady decline in visual acuity from an average of 0.23 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/34) at baseline to 0.42 logMAR (Snellen equivalent, 20/53) at the final visit, whereas TFPD patients maintained excellent acuity throughout follow-up. Participants with LCHADD, but not TFPD, showed an increasing myopia with a mean decrease in spherical equivalent refraction of 0.24 diopters per year. Visual fields showed sensitivity losses centrally associated with defects on OCT. Multimodal imaging demonstrated progressive atrophy of the outer retina in LCHADD, often preceded by the formation of outer retinal tubulations and choriocapillaris dropout. Electroretinography findings support the more severe clinical profile of LCHADD patients compared with TFPD patients; the function of both rods and cones are attenuated diffusely in LCHADD patients, but are within normal limits for TFPD patients.Despite improved survival with early diagnosis, medical management, and dietary treatment, participants with the LCHADD subtype of MTP disorder continue to demonstrate visually disabling chorioretinopathy. Multimodal imaging is most consistent with choriocapillaris loss exceeding photoreceptor loss.

OBJECTIVE: Recent US Preventive Services Task Force recommendations on vision screening reported insufficient data to recommend vision screening in children METHODS: A retrospective review of results from the Iowa KidSight database using the MTI PhotoScreener containing results of children screened between May 1, 2000, and April 30, 2011. RESULTS: During the 11 years of the study, 210 695 photoscreens on children were performed at 13 750 sites. In the CONCLUSIONS: No statistically significant difference was found in screening children from 1 to 3 years old compared with screening children >3 years old. These results confirm that early screening, before amblyopia is more pronounced, can reliably detect amblyogenic risk factors in children younger than 3 years of age, and we recommend initiation of photoscreening in children aged 1 year and older.