Zonular fibre Insertion-to-Limbus Distance (ZLD): normative data to assess lens position and diagnose ectopia lentis.

PURPOSE: Subluxation of the crystalline lens (Ectopia Lentis, EL) can lead to significant visual impairment and serves as a diagnostic criterion for genetic disorders such as the Marfan syndrome. There is no established criterion to diagnose and quantify EL. We prospectively investigated the distance between the zonular fibre insertion and the limbus (ZLD) in healthy subjects as a parameter to assess the position of the lens, quantify EL and provide normative data. METHODS: This prospective, observational, cross-sectional study includes one-hundred-fifty eyes of 150 healthy participants (mean age 28 years, range 4-68). Pupils were dilated with tropicamide 0.5% and phenylephrine 2.5% eyedrops. ZLD was measured in mydriasis at the slit lamp as the distance between the most central visible insertions of the zonular fibres on the lens surface and the corneoscleral limbus. Vertical pupil diameter (PD) and refractive error were recorded. If zonular fibre insertions were not visible, the distance between limbus and the pupillary margin was recorded as ZLD. RESULTS: 145 right and 5 left eyes were examined. 93% of study subjects were Caucasian, 7% were Asian. In eyes with visible zonular fibre insertions (n = 76 eyes), ZLD was 1.30 ± 0.28 mm (mean ± SD, range 0.7-2.1) and PD was 8.79 ± 0.57 mm (7.5-9.8). In the remaining 74 eyes, ZLD was 1.38 ± 0.28 mm (0.7-2.1), and PD was 8.13 ± 0.58 mm (6.7-9.4). For all eyes, ZLD was 1.34 ± 0.29 mm (0.7-2.1), and PD was 8.47 ± 0.66 mm (6.7-9.8). Refractive error and sex did not significantly affect ZLD. Smaller PD and older age were associated with larger ZLD (P < 0.001 and P = 0.036, respectively). CONCLUSION: Average ZLD was 1.34 mm in eyes of healthy subjects. Older age correlated with larger ZLD. These normative data will aid in diagnosing and quantifying EL.

[Nystagmus in Children - a Survey]. / Nystagmus bei Kindern ­ eine Übersicht.

Nystagmus describes an involuntary, periodic movement of one or both eyes. About 1/600 children and adolescents have nystagmus, most of them idiopathic infantile nystagmus (IIN), also called "congenital nystagmus", which can be caused by mutations in the FRMD7 gene. Other frequent forms of nystagmus are latent nystagmus, which is usually associated with infantile strabismus, and nystagmus associated with albinism. Sometimes difficult to distinguish in young infants is a sensory nystagmus, where a defect in the visual system reduces vision and causes nystagmus. Causes include retinal dystrophies, congenital stationary night blindness and structural ocular defects including optic nerve hypoplasia or dense bilateral congenital cataracts. Unilateral nystagmus can be the sign of an anterior visual pathway lesion. Seesaw nystagmus may be associated with suprasellar and mesodiencephalic lesions and - rarely - with retinal dystrophies.The ophthalmology plays a key role in identifying the form of nystagmus. Children with new onset nystagmus, with spasmus nutans, with vertical or unilateral nystagmus and those with seesaw nystagmus require neurologic evaluation including imaging of the brain.The treatment of nystagmus depends on the underlying cause. Even minor refractive errors should be corrected, contact lenses offer advantages over glasses.Gabapentin and memantine, possibly also carbonic anhydrase inhibitors, are effective in treating IIN, nystagmus in albinism and sensory nystagmus. Nevertheless, pharmacologic treatment of nystagmus is rarely used in children; the reasons are the limited effects on vision, the need for lifelong therapy, and potential side effects. Eye muscle surgery (Anderson procedure, Kestenbaum procedure) can correct a nystagmus-related anomalous head posture. The concept of "artifical divergence" of Cüppers may help to decrease nystagmus intensity in patients whose nystagmus dampens with convergence. The four-muscle-tenotomy, which involves disinsertion and reinsertion of the horizontal muscles at the original insertion of both eyes, has a proven but limited positive effect on visual acuity.

Tumor load rather than contrast enhancement is associated with the visual function of children and adolescents with optic pathway glioma - a retrospective Magnetic Resonance Imaging study.

INTRODUCTION: Optic pathway gliomas are often asymptomatic tumors occurring in children with neurofibromatosis type 1 (NF1 + OPG) or sporadically (spOPG). Treatment is usually prompted by visual loss and/or tumor progression on MRI. The aim of this study was to investigate the relationship between visual acuity (VA), tumor growth, and contrast enhancement to provide more distinct indications for the administration of gadolinium-based contrast agents. METHODS: Tumor load was retrospectively measured and enhancement semi-quantitatively scored on 298 MRIs of 35 patients (63% NF1 + OPG). Spearman rank correlation between tumor load and enhancement was calculated and a linear mixed model used to examine the influence of tumor load and enhancement on corresponding VA tests (LogMAR). RESULTS: The optic nerve width in NF1 + OPGs was strongly associated with VA (regression coefficient 0.75; confidence interval 0.61-0.88), but weakly with enhancement (0.06; -0.04-0.15). In spOPGs, tumor volume and optic nerve width were more relevant (0.31; -0.19-0.81 and 0.39; 0.05-0.73) than enhancement (0.09; -0.09-0.27). CONCLUSIONS: Tumor load measures may be more relevant for the surveillance of optic pathway gliomas than enhancement, given that VA is the relevant outcome parameter. Regular contrast administration should therefore be questioned in these patients.

De novo mutation in ELOVL1 causes ichthyosis, acanthosis nigricans, hypomyelination, spastic paraplegia, high frequency deafness and optic atrophy.

BACKGROUND: Very long-chain fatty acids (VLCFAs) are essential for functioning of biological membranes. ELOVL fatty acid elongase 1 catalyses elongation of saturated and monounsaturated C22-C26-VLCFAs. We studied two patients with a dominant ELOVL1 mutation. Independently, Kutkowska-Kazmierczak et al. had investigated the same patients and found the same mutation. We extended our study towards additional biochemical, functional, and therapeutic aspects. METHODS: We did mutation screening by whole exome sequencing. RNA-sequencing was performed in patient and control fibroblasts. Ceramide and sphingomyelin levels were measured by LC-MS/MS. ELOVL1 activity was determined by a stable isotope-labelled [13C]malonyl-CoA elongation assay. ELOVL1 expression patterns were investigated by immunofluorescence, in situ hybridisation and RT-qPCR. As treatment option, we investigated VLCFA loading of fibroblasts. RESULTS: Both patients carried an identical heterozygous de novo ELOVL1 mutation (c.494C>T, NM_001256399; p.S165F) not deriving from a founder allele. Patients suffered from epidermal hyperproliferation and increased keratinisation (ichthyosis). Hypomyelination of the central white matter explained spastic paraplegia and central nystagmus, while optic atrophy was causative for reduction of peripheral vision and visual acuity. The mutation abrogated ELOVL1 enzymatic activity and reduced ≥C24 ceramides and sphingomyelins in patient cells. Fibroblast loading with C22:0-VLCFAs increased C24:0-ceramides and sphingomyelins. We found competitive inhibition for ceramide and sphingomyelin synthesis between saturated and monounsaturated VLCFAs. Transcriptome analysis revealed upregulation of modules involved in epidermal development and keratinisation, and downregulation of genes for neurodevelopment, myelination, and synaptogenesis. Many regulated genes carried consensus proliferator-activated receptor (PPAR)α and PPARγ binding motifs in their 5'-regions. CONCLUSION: A dominant ELOVL1 mutation causes a neuro-ichthyotic disorder possibly amenable to treatment with PPAR-modulating drugs.

[Orbital Disorders in Childhood]. / Orbitaerkrankungen im Kindesalter.

Orbital disorders in childhood include various pathologies. Whereas neoplastic lesions and structural anomalies (which frequently cause strabismus) predominate in newborns and infants, vascular lesions become more common in toddlers. Inflammatory lesions are less common than in adults and affect mostly older children and adolescents. The most common orbital mass in infants and young children is a dermoid cyst, a benign lesion.Rhabdomyosarcoma as the most common primary orbital malignancy and neuroblastoma as a common metastasis to the orbit should be considered in children with new onset orbital space-occupying lesions.Capillary hemangioma and lymphangioma (lymphatic malformation) are relatively common vascular orbital lesions in children. Novel therapeutic options include systemic betablockers for capillary hemangioma and sirolimus for lymphangioma. In contrast to adults, external signs of an orbital fracture may be absent or mild in children. If ocular motility restriction after orbital trauma is present in a child without obvious external signs, a "white-eye blowout fracture" of the orbit should be considered and requires prompt surgical repair if present.Inflammatory disorders of the orbit such as thyroid-related orbitopathy and idiopathic orbital inflammation are uncommon in young children and occur more frequently in adolescents. In young children, amblyopia may complicate any orbital disease. It should be treated using part-time occlusion or pharmacologic penalisation of the fellow eye and the underlying cause should be addressed.

Activation of a Ca2+-dependent cation conductance with properties of TRPM2 by reactive oxygen species in lens epithelial cells.

Ion channels are crucial for maintenance of ion homeostasis and transparency of the lens. The lens epithelium is the metabolically and electrophysiologically active cell type providing nutrients, ions and water to the lens fiber cells. Ca2+-dependent non-selective ion channels seem to play an important role for ion homeostasis. The aim of the study was to identify and characterize Ca2+- and reactive oxygen species (ROS)-dependent non-selective cation channels in human lens epithelial cells. RT-PCR revealed gene expression of the Ca2+-activated non-selective cation channels TRPC3, TRPM2, TRPM4 and Ano6 in both primary lens epithelial cells and the cell line HLE-B3, whereas TRPM5 mRNA was only found in HLE-B3 cells. Using whole-cell patch-clamp technique, ionomycin evoked non-selective cation currents with linear current-voltage relationship in both cell types. The current was decreased by flufenamic acid (FFA), 2-APB, 9-phenanthrol and miconazole, but insensitive to DIDS, ruthenium red, and intracellularly applied spermine. H2O2 evoked a comparable current, abolished by FFA. TRPM2 protein expression in HLE-B3 cells was confirmed by means of immunocytochemistry and western blot. In summary, we conclude that lens epithelial cells functionally express Ca2+- and H2O2-activated non-selective cation channels with properties of TRPM2.

Influence of chloroquine intake on the multifocal electroretinogram in patients with and without maculopathy.

PURPOSE: To evaluate the effect of long-term chloroquine intake on the multifocal electroretinogram (mfERG) in female patients with and without maculopathy. METHODS: Retrospective analysis of the mfERGs recorded in three different groups: (1) patients with bilateral maculopathy having taken chloroquine, (2) patients without maculopathy having taken chloroquine, and (3) healthy control subjects (age-matched to group 2) who never took chloroquine. MfERGs of each group were averaged, and the data of each patient group were compared to the control group. The main outcome measures were N1 and P1 characteristics and the ring ratio analysis. RESULTS: In group 1, 11 female subjects (22 eyes) were included, group 2 consisted of nine patients (18 eyes) and group 3 of seven healthy female subjects (14 eyes). Compared with healthy controls, patients in group 1 showed significantly reduced response densities of both N1 and P1 across all ring eccentricities except ring 5. Implicit times were significantly delayed only concerning N1 (ring 4 and the sum response of the left eye of group 1). P1 implicit times showed no significant alterations in either group. Ring ratios of the response densities were significantly higher mainly concerning group 1 (N1: ring 5/ring 2 and ring 5/ring 4 of the right eye; P1: all ring ratios of the right eye and all ratios except ring 5/ring 1 and ring 5/ring 4 of the left eye). The only ring ratio being significantly higher in group 2 was P1 ring 5/ring 1 ratio of the right eye. CONCLUSIONS: In the absence of clinically apparent maculopathy, chloroquine intake was not associated with major alterations of the mfERG.

Differentials and approach to leukocoria.

Leukocoria is an important clinical examination finding as it can be a sign of significant intraocular pathology, with the most common being retinoblastoma and congenital cataracts. The Brückner test is a quick, easy, and inexpensive way to assess the red reflex. When leukocoria is suspected, prompt referral to an ophthalmologist is necessary for further evaluation.

[Detections of refractive risk factors for amblyopia with Plusoptix Autorefractor A09]. / Erkennung refraktiver Amblyopierisikofaktoren mittels Plusoptix Autorefractor A09.

BACKGROUND: Amblyopia is the most frequent cause for decreased vision in childhood. Important risk factors for amblyopia (ARF) are refractive errors. The aim of this study was to examine the reliability of the Plusoptix Autorefractor A09 (POA09) to detect refractive ARF. METHOD: This prospective non-blinded, one-armed study was conducted between February 2012 and September 2015. Children aged 6 months to 12 years were screened in kindergarten and schools for refractive errors. Thresholds for screening failure were hyperopia ≥ 3.5 diopters (D), myopia ≥ 3.0 D, anisometropia ≥ 1.5 D and astigmatism ≥ 1.5 D (axis 90° or 180°â€¯± 10°) or ≥ 1.0 D (≥ 10° axis deviation of 90° or 180°). Children who failed screening were advised to see an ophthalmologist for a comprehensive eye examination. After the visit, parents were asked for the results of the examination. A reference group of children who did not fail screening also received a comprehensive eye examination. Based on the number of children who failed screening, we calculated the proportion of correctly detected refractive errors. Based on the children of the reference group we calculated the proportion of correctly excluded refractive errors and the false negative rate. RESULTS: In this study 3170 children were screened, 715 children (22.3%) failed screening. For 460 of these (64.3%) follow-up was available and for 132 children information on refractive errors in cycloplegia was available. Most frequent refractive errors at screening were astigmatism (90.9%) and anisometropia (11.4%). Most frequent refractive errors in cycloplegia were astigmatism (56.8%) and hyperopia (18.9%). The proportion of correctly detected refractive errors in the screening was highest for astigmatism (60%) and anisometropia (53.3%), followed by hyperopia (33.3%) and myopia (25%). CONCLUSION: The reliability of POA09 to detect refractive ARF in children without cycloplegia was limited, highlighting the importance of a systematic amblyopia screening. A screening in cycloplegia can increase the proportion of correctly detected refractive ARF and should be studied.

Gene Therapy with Voretigene Neparvovec Improves Vision and Partially Restores Electrophysiological Function in Pre-School Children with Leber Congenital Amaurosis.

Leber congenital amaurosis caused by mutations in the RPE65 gene belongs to the most severe early-onset hereditary childhood retinopathies naturally progressing to legal blindness. The novel gene therapy voretigene neparvovec is the first approved causative treatment option for this devastating eye disease and is specifically designed to treat RPE65-mediated retinal dystrophies. Herein, we present a follow-up of the youngest treated patients in Germany so far, including four pre-school children who received treatment with voretigene neparvovec at a single treatment center between January 2020 and May 2022. All patients underwent pars plana vitrectomy with circumferential peeling of the internal limiting membrane at the injection site and subretinal injection of voretigene neparvovec. Pre- and postoperative diagnostics included imaging (spectral domain optical coherence tomography, fundus autofluorescence, fundus wide-angle imaging), electrophysiologic examination (ERG), retinal light sensitivity measurements (FST) and visual acuity testing. Behavioral changes were assessed using a questionnaire and by observing the children's vision-guided behavior in different levels of illumination. All children showed marked increase in vision-guided behavior shortly after therapy, as well as marked increase in visual acuity in the postoperative course up to full visual acuity in one child. Two eyes showed partial electrophysiological recovery of an ERG that was undetectable before treatment-a finding that has not been described in humans before.

Abducens neuromyotonia as the presenting sign of an intracranial tumor.

In this case series and review of the literature, we describe 2 cases of abducens neuromyotonia (ANM) as the presenting sign of an intracranial tumor (meningioma). Review of the literature suggests that the pathophysiology of ocular neuromyotonia is incompletely understood. Most patients with ANM have a history of radiation therapy. The diagnosis of ANM is made on the basis of clinical findings and can be supported by electrophysiological studies. A complete neurologic examination is mandatory for patients with ANM. Treatment consists of eliminating the underlying cause; carbamazepine is effective in alleviating the symptoms of ANM. Neuroimaging should be performed if patients with ANM lack the typical history of radiation therapy, as ANM may be the presenting sign of an intracranial mass.

Effect of unilateral vertical transposition of the horizontal rectus muscles on vertical strabismus.

PURPOSE: To study the effect of vertically transposing both horizontal eye muscles of one eye in the same direction on vertical strabismus. METHODS: Retrospective analysis of 33 patients in whom vertical transposition of the medial and lateral rectus muscles was combined with a recession/resection or recession/plication procedure. Preoperative ocular alignment was compared with that 1 day and 3 months postoperatively. RESULTS: Mean preoperative vertical deviation was 7.8 ± 4.3 (median 7.5, range 3-25) prism diopters (PD) at distance and 7.8 ± 4.1 (7, 0-18) PD at near. Vertical transposition of the horizontal rectus muscles averaged 5.6 ± 1.6 mm and reduced the vertical deviation to 3.4 ± 4.2 PD (2, 0-16) at distance and 2.9 ± 3.7 PD (2, 0-14) at near. Mean effect on the vertical deviation was 0.9 ± 0.7 (0.8, -0.8 to 2.13) PD/mm at distance and 0.9 ± 0.9 (0.83, -1 to 3) PD/mm at near, it was similar in patients operated on for esotropia and for exotropia. The surgical effect on the horizontal deviation was 2.1 ± 1.1 PD/mm (distance) and 2.6 ± 1 PD/mm (near). Both the vertical and horizontal surgical dose correlated with the effect in a linear way, but the variability was greater for the vertical transposition. CONCLUSIONS: Vertical transposition of the horizontal rectus muscles in the same direction allows for correction of vertical strabismus. This procedure may be performed during primarily horizontal strabismus surgery, without operating on an additional extraocular muscle. The transposition distance correlates with the surgical effect but predictability of the effect is limited.

Strabismus patterns after cataract surgery in adults.

New-onset binocular diplopia after cataract surgery in adults is a rare but significant complication. The aim of this study was to analyze causes, risk factors, and treatment outcomes. Forty consecutive patients with new-onset binocular diplopia after uncomplicated cataract surgery were enrolled in this retrospective study at a tertiary medical center. We evaluated risk factors including type of anesthesia, preoperative presence of strabismus, and others regarding their effect on the development of diplopia after cataract surgery. We further analyzed ocular alignment and motility at presentation and during the clinical course. The majority of the patients with new-onset diplopia presented after cataract surgery on the left eye (28 of 40). Vertical strabismus occurred in 37 of 40 patients, and regional (peri- or retrobulbar) anesthesia was the main risk factor for postoperative diplopia (present in 37 of 40). There were four distinct ocular dysmotility patterns in patients with vertical strabismus: deficient elevation with (type 1a) or without over-depression (type 1b), deficient depression (type 2), or normal motility (type 3). After surgery of the right eye, most patients (6 of 9) showed type 2. After cataract surgery on the left eye, type 1a was most common (20 of 24). Three patients had horizontal strabismus due to a decompensated heterophoria or convergence insufficiency. In total, 17 patients required strabismus surgery (mean 1.3 operations, range 1-3). Regional anesthesia was the main risk factor for new-onset diplopia after cataract surgery in adults. Distinct strabismus patterns were observed for left and right eyes.d.

Firework-inflicted ocular trauma in children and adults in an urban German setting.

PURPOSE: To assess firework-inflicted ocular trauma in the German capital during the week around New Year's Eve with regards to patient characteristics and age, severity of injuries, and their management and outcome. METHODS: A retrospective chart review of all patients presenting to the department of ophthalmology of Charité-University Medicine Berlin during a 7-day period around New Year's Eve in the years 2014-2017 was performed. Patients with ocular complaints and injuries caused by fireworks were included. We recorded demographic data, active role, visual acuity at presentation and at last follow-up, the most pertinent clinical findings, management and outcome with regards to visual acuity, and integrity of the eye. RESULTS: A total of 146 patients with 165 injured eyes were included. Median age at presentation was 23 (4-58) years, and 71.2% were male. Fifty-one patients (34.9%) were less than 18 years old. Ninty-seven patients (66.4%) sustained minor, 34 (23.3%) sustained moderate, and 15 (10.3%) sustained severe injuries. Severe trauma was seen in younger patients (median age: 12, range: 4-58 years) than mild and moderate trauma (median age: 23, range: 4-45 years) and resulted in loss of light perception in two eyes and in a visual acuity of only light perception in three eyes. One eye was enucleated. CONCLUSION: Ocular trauma inflicted by fireworks can have serious consequences for ocular morbidity and visual acuity, especially in severe trauma which affected younger patients. To significantly reduce firework-inflicted trauma, a ban of private fireworks in densely populated areas and in the vicinity of children should be considered.

Absent optic chiasm presenting with horizontal nystagmus.

A female infant with horizontal nystagmus and normal ophthalmic examination had isolated absence of the optic chiasm on magnetic resonance imaging. Eye movements were recorded on video and reviewed. Horizontal nystagmus without see-saw nystagmus was observed. Visual evoked potential showed inter-hemispheric asymmetry compatible with the absence of crossing chiasmal fibers. Systemic abnormalities in this patient included cleft lip, preauricular skin tags, broad thumbs, and an anteriorly positioned anus, suggestive of Townes-Brock syndrome.

Outcome of a penetrating keratoplasty in a 3-month-old child with sclerocornea.

Sclerocornea is a rare congenital anomaly with clouding of the peripheral cornea that possibly extends up to the center of the cornea. Characteristically, a clear distinction (limbus) between sclera and cornea is lacking. Early surgical treatment is essential for preventing amblyopia, but penetrating keratoplasty in children carries a relatively high risk of complications. Especially for sclerocornea, penetrating keratoplasty has generally been reported to have a poor surgical outcome and a high risk of complications, including corneoscleral adhesions. Here, we report the 4-year follow-up on a child with sclerocornea, who was successfully operated on at the age of 3 months and had a favorable outcome. Our findings suggest that in some cases, penetrating keratoplasty may be an option to treat sclerocornea in young children.

Propofol Modulates Early Memory Consolidation in Humans.

Maintenance of memory across time is crucial for adaptive behavior. Current theories posit that the underlying consolidation process depends on stabilization of synapses and reorganization of interactions between hippocampus and neocortex. However, the temporal properties of hippocampal-neocortical network reconfiguration during consolidation are still a matter of debate. Translational research on this issue is challenged by the paucity of techniques to transiently interfere with memory in the healthy human brain. Here, we report a neuro-pharmacological approach with the GABAAergic anesthetic propofol and a memory task sensitive to hippocampal dysfunction. Patients undergoing minor surgery learned word lists before injection of an anesthetic dose of propofol. Results show that administration of the drug shortly after learning (∼13 min) impairs recall after awakening but spares recognition. By contrast, later administration (∼105 min) has no effect. These findings suggest significant changes in memory networks very early after learning that are decisive for later recall. Propofol general anesthesia provides an experimental tool to modulate the first steps of hippocampus-mediated memory consolidation in humans.

Ocular manifestations of Marfan syndrome in children and adolescents.

PURPOSE:: To study ocular manifestations of Marfan syndrome in children and adolescents. METHODS:: Retrospective comparative cohort study on consecutive patients up to age 17 years, presenting to the interdisciplinary Marfan clinic of Charité-University Medicine Berlin over a period of 4 years. RESULTS:: A total of 52 Marfan syndrome patients and 73 controls were enrolled. In Marfan syndrome eyes, the cornea was flatter (mean keratometry, 40.86 ± 2.13 vs 42.55 ± 1.55 diopters in control eyes, p < .001) and corneal astigmatism was greater (1.50 ± 1.22 vs 0.88 ± 0.49 diopters in control eyes, p < .001). The central cornea was thinner in Marfan syndrome eyes (537.35 ± 40.64 vs 552.95 ± 38.57 µm, p = 0.007) and Marfan syndrome eyes were more myopic than control eyes (spherical equivalent, -2.77 ± 4.77 vs -0.64 ± 1.92 diopters, p < .001). Visual acuity was reduced (logMAR 0.11 ± 0.17 vs 0.04 ± 0.26, p = 0.014) and intraocular pressure was lower in Marfan syndrome eyes. Iris transillumination defects were more common in Marfan syndrome eyes (19.6% vs 4.3% in control eyes, odds ratio for Marfan syndrome in the presence of iris transillumination defects = 7.2). Ectopia lentis was only found in Marfan syndrome eyes (25 Marfan syndrome patients, 49% with available data, bilateral in 68%). CONCLUSION:: Iris transillumination defects and ectopia lentis are characteristic ocular findings in children and adolescents with Marfan syndrome. Myopia is more common and corneal curvature, central corneal thickness, and visual acuity are reduced in Marfan syndrome eyes. Children with Marfan syndrome need regular comprehensive eye examinations to identify potential complications.

Epithelial-Mesenchymal Transdifferentiation in Pediatric Lens Epithelial Cells.

Purpose: Posterior capsule opacification (PCO) is a complication after cataract surgery, particularly in children. Epithelial-mesenchymal transition (EMT) of lens epithelial cells, mediated by transforming growth factor beta (TGFß), contributes to PCO. However, its pathogenesis in children is poorly understood. We correlated cell growth in culture with patient characteristics, studied gene expression of pediatric lens epithelial cells (pLEC), and examined the effects of TGFß-2 on these cells in vitro. Methods: Clinical characteristics of children with cataracts correlated with growth behavior of pLEC in vitro. mRNA expression of epithelial (αB-crystallin, connexin-43) and mesenchymal (αV-integrin, α-smooth muscle actin, collagen-Iα2, fibronectin-1) markers was quantified in pLEC and in cell line HLE-B3 in the presence and absence of TGFß-2. Results: Fifty-four anterior lens capsules from 40 children aged 1 to 180 months were obtained. Cell outgrowth occurred in 44% of the capsules from patients ≤ 12 months and in 33% of capsules from children aged 13 to 60 months, but in only 6% of capsules from children over 60 months. TGFß-2 significantly upregulated expression of αB-crystallin (HLE-B3), αV-integrin (HLE-B3), collagen-Iα2, and fibronectin-1 (in pLEC and HLE-B3 cells). Conclusions: Patient characteristics correlated with growth behavior of pLEC in vitro, paralleling a higher clinical incidence of PCO in younger children. Gene expression profiles of pLEC and HLE-B3 suggest that upregulation of αV-integrin, collagen-Iα2, and fibronectin-1 are involved in EMT.

Ocular findings in Loeys-Dietz syndrome.

BACKGROUND: Loeys-Dietz syndrome (LDS), an autosomal-dominant connective tissue disorder, is characterised by systemic manifestations including arterial aneurysm and craniofacial dysmorphologies. Although ocular involvement in LDS has been reported, detailed information on those manifestations is lacking. METHODS: Retrospective chart review of patients with diagnosed LDS and comparison with age-matched control patients. RESULTS: Mean age was 37.8±14.6 years (patients with LDS) and 38.4±13.5 years (controls). Patients with LDS less frequently had iris transillumination, cataract and glaucoma compared with controls. Scleral and retinal vascular abnormalities were not found in any of the LDS eyes. Ectopia lentis was found in one patient with LDS. The eyes of patients with LDS tended to be more myopic (spherical equivalent, -2.47±2.70 dioptres (dpt) vs -1.30±2.96dpt (controls); P=0.08) and longer (24.6±1.7mm vs 24.1±1.5mm (controls); P=0.10). Central corneal thickness was significantly reduced in LDS eyes (521±48µm vs 542±37µm (controls); P=0.02). Corneal curvature (43.06±1.90dpt (LDS) versus 43.00±1.37dpt (controls); P=0.72) and interpupillary distance (65.0±6.0mm (LDS) vs 64.3±4.8mm (controls); P=0.66) did not differ significantly between both groups. Visual acuity was similar between both groups (0.03±0.09logarithm of the minimum angle of resolution (logMAR) for LDS eyes and 0.05±0.17logMAR for control eyes, P=0.47). CONCLUSIONS: Ocular features of LDS include decreased central corneal thickness and mild myopia. Ectopia lentis may be slightly more common than in controls but appears less common than in Marfan syndrome. Hypertelorism, scleral and retinal vascular abnormalities were not features of LDS.