A Modified Bicanalicular Crawford Placement Method for Congenital Nasolacrimal Duct Obstruction: Reducing Need for Operative Room Removal.

PURPOSE: This study introduces a method for Crawford bicanalicular stent placement for congenital nasolacrimal duct obstruction by looping the ends to themselves which are tied together with dissolvable sutures to ease in-office removal. METHODS: This is a single institution, retrospective study that evaluates outcomes of patients aged 5 years and under who underwent bicanalicular stenting for congenital nasolacrimal duct obstruction by a single surgeon (G.S.E.) between 2004 and 2020. Only primary surgeries were included in the analysis. Stenting could be accompanied by balloon dilatation and/or turbinate infracture. Age, sex, follow-up time, complications, type of intervention, extrusion, recurrence, and operative room removal were recorded. RESULTS: This study included 56 eyes from 54 patients with a mean age of 19.0 ± 9.5 months (range, 8-50 months). There was a 30.3% extrusion rate, a 5.4% rate of recurrence of disease, and a 3.6% rate of operative room removal. The average follow-up time was 25.1 ± 39.8 months (range, 1-132 months). For patients with or without extrusion, there were no significant differences between age, sex, laterality, type of intervention, follow-up time, or rate of recurrence. Each eye that had recurrence (3 total) or needed operative room removal (2 total) underwent only bicanalicular stenting without accompanying procedures, although the difference in rates between procedures was also not statistically significant. CONCLUSIONS: This method had a low recurrence and operative room removal rate, with similar extrusion and complication rates to other bicanalicular stent and intubation methods for the treatment of congenital nasolacrimal duct obstruction.

The Axenfeld-Rieger Syndrome Gene FOXC1 Contributes to Left-Right Patterning.

Precise spatiotemporal expression of the Nodal-Lefty-Pitx2 cascade in the lateral plate mesoderm establishes the left-right axis, which provides vital cues for correct organ formation and function. Mutations of one cascade constituent PITX2 and, separately, the Forkhead transcription factor FOXC1 independently cause a multi-system disorder known as Axenfeld-Rieger syndrome (ARS). Since cardiac involvement is an established ARS phenotype and because disrupted left-right patterning can cause congenital heart defects, we investigated in zebrafish whether foxc1 contributes to organ laterality or situs. We demonstrate that CRISPR/Cas9-generated foxc1a and foxc1b mutants exhibit abnormal cardiac looping and that the prevalence of cardiac situs defects is increased in foxc1a-/-; foxc1b-/- homozygotes. Similarly, double homozygotes exhibit isomerism of the liver and pancreas, which are key features of abnormal gut situs. Placement of the asymmetric visceral organs relative to the midline was also perturbed by mRNA overexpression of foxc1a and foxc1b. In addition, an analysis of the left-right patterning components, identified in the lateral plate mesoderm of foxc1 mutants, reduced or abolished the expression of the NODAL antagonist lefty2. Together, these data reveal a novel contribution from foxc1 to left-right patterning, demonstrating that this role is sensitive to foxc1 gene dosage, and provide a plausible mechanism for the incidence of congenital heart defects in Axenfeld-Rieger syndrome patients.

Mosaic cat eye syndrome in a child with unilateral iris coloboma.

BACKGROUND: Cat eye syndrome (CES) is a rare chromosomal disorder with a known incidence of 1 per 50,000-150,000 live newborns. The classic triad of iris coloboma, anorectal malformations, and auricular abnormalities is present in 40% of patients. In addition, other ocular malformations and systemic defects can be present. The aim of this report is to present a patient with unilateral iris coloboma related to a mosaicism of cat eye syndrome. METHODS: A complete ophthalmological and systemic evaluation was performed in a three-year-old male. He also underwent a standard karyotype and FISH analysis with a probe against the 22q11.2 locus. RESULTS: The ophthalmological and systemic evaluation revealed a unilateral iris coloboma and ipsilateral auricular malformations. Karyotype analysis of blood leukocytes indicated the presence of a marker chromosome in 6% of the analyzed cells. FISH analysis showed three positive signals in 5.5% of the analyzed nucleus. CONCLUSION: This patient presented two of the three classic manifestations of CES; interestingly, they were unilateral. The 22q11 duplication was identified by standard karyotype and confirmed with FISH. The present case demonstrates the importance of conducting a multidisciplinary approach in patients with congenital malformations associated with known syndromes.

Scleroderma en Coup de Sabre, Parry-Romberg Hemifacial Atrophy and Associated Manifestations of the Eye, the Oral Cavity and the Teeth: A Danish Follow-Up Study of 35 Patients Diagnosed between 1975 and 2015.

BACKGROUND: Scleroderma en coup de sabre (ECDS) and Parry-Romberg idiopathic hemifacial atrophy (IHA) may affect the eyes, oral cavity, teeth and possibly the brain. OBJECTIVE: Systematic follow-up study of ECDS/IHA-associated manifestations including ophthalmic and dental status. METHODS: Medical records of ECDS and IHA patients diagnosed in a 40-year period (1975-2015) were reviewed, and patients were re-examined. RESULTS: Thirty-five patients were included. Twenty-two patients (63%) had ECDS and 4 patients (11%) IHA. In 9 cases (26%), ECDS and IHA were found in the same patient. The ipsilateral eye was affected in 9 patients (26%). Ipsilateral abnormalities of the teeth and the tongue were found in 13 (46%) out of 28 examined. Eleven (31%) had extrafacial scleroderma on the trunk or the extremities. Neurological findings were not verified as ECDS/IHA related. CONCLUSION: ECDS and IHA are related and often overlap with concomitant affections of the connective tissues of the face on the ipsilateral side. Ocular and dental abnormalities are common and follow the distribution of the primary affection, for example, a paramedian line in the front and segmental affection of the maxilla and the mandible. The affections point to predisposing dysmorphogenetic events in embryonal life affecting the face, with abnormality of crest cells at the stage when they migrate from behind over the scalp or laterally to the face to mix up with mesenchymal tissues of the frontonasal, maxillary and mandibular processes. The study emphasizes that routine evaluation of ECDS and IHA should include ophthalmological and dental specialist examinations.

Large choroidal excavation in pachychoroid disease: A case report.

PURPOSE: To report the morphological and clinical features of a case of pachychoroid disease with focal choroidal excavation and large choroidal excavation complicated by choroidal neovascularization. METHODS: The patient underwent a complete ophthalmologic examination including best-corrected visual acuity assessment, anterior segment and dilated fundus examination, fluorescein and indocyanine green angiography, and spectral-domain optical coherence tomography. RESULTS: During the previous follow-up, the 57-year-old man received a diagnosis of central serous chorioretinopathy in the right eye with a late appearance of a choroidal neovascularization. The best-corrected visual acuity was 20/125 and 20/20 in the right and left eye, respectively. Dilated fundus examination, fluorescein angiography, and indocyanine green angiography confirmed a large subretinal fibrosis corresponding to the evolution of the choroidal neovascularization in the right eye. Spectral-domain optical coherence tomography clearly demonstrated in the right eye a large choroidal excavation below the fibrotic neovascular lesion with multiple hyperreflective foci inside the cavity, and in the left eye, a conforming focal choroidal excavation, bowl-shape type, associated with increased choroidal thickness with pachyvessels. CONCLUSION: Large choroidal excavation has been rarely reported. Although the pathogenetic mechanisms leading to the formation of large choroidal excavation are still only hypotheses, a combination of primary degenerative inflammatory factors sustaining the focal choroidal excavation formation and disruptive process of the choroidal neovascularization could be retained responsible for the large choroidal excavation.

3-D assessment of gaze-induced eye shape deformations and downgaze-induced vitreous chamber volume increase in highly myopic eyes with staphyloma.

PURPOSE: To determine if the stress of normal eye movements results in gaze-induced globe deformations, vitreous chamber axial length and vitreous chamber axial volume (VCAV) change in highly myopic eyes. METHODS: A prospective imaging study was performed on 82 eyes of 43 patients with high myopia (>27 mm of axial length) with a clinical diagnosis of staphyloma. Three-dimensional MRI scans were acquired while subjects gazed in five directions (primary, nasal, temporal, superior and inferior). Surface renderings were generated, and a processing pipeline was created to automate alignment of the eye and to measure VCAV within 5.5 mm of the visual axis for each eye in every gaze. The degree of gaze-induced globe deformation was determined by calculating the Dice coefficient to assess the degree of overlap of the sclera at each eccentric gaze with that found in primary gaze. Each eccentric gaze VCAV was compared to VCAV in primary gaze using a fixed-effects regression allowing for subject-specific and eye-specific effects. RESULTS: The Dice coefficient showed significant gaze-induced eye shape changes in all gazes (all p<0.0001). There were no statistically significant gaze-induced VCAV changes when comparing primary gaze to nasal, temporal or upgaze. However, when changing from primary to downgaze, VCAV was increased by +4.79 mm3 (p=0.002, 95% CI 1.71 to 7.86). CONCLUSION: Significant gaze-induced globe deformation was noted in all gazes, but a reversible, instantaneous VCAV increase occurred only in downgaze, which is consistent with studies supporting the association of environmental factors such as near work with myopia development and progression.

Focal choroidal excavation: review of literature.

Focal choroidal excavation (FCE) is defined as an area of concavity in choroid detected on optical coherence tomography. These are mostly present in macular region without evidence of accompanying scleral ectasia or posterior staphyloma. Though initially considered to be congenital, increasing number of cases have been identified in association with other choroidal pathologies such as central serous choroidopathy, choroidal neovascularisation, polypoidal choroidal vasculopathy, choroiditis, choroidal tumours. In this review article, we aim to elaborate on the morphology, pathogenesis and differential diagnosis of FCE and specifically discuss the spectrum of diseases with known association along with the impact of their treatment on FCE.

Novel biallelic loss-of-function variants in CEP290 cause Joubert syndrome in two siblings.

BACKGROUND: Joubert syndrome (JS) is a rare genetic disorder, which can be defined by brain stem malformation, cerebellar vermis hypoplasia, and consequent "molar tooth sign" (MTS). JS always shares variety of phenotypes in development defects. With the development of next-generation sequencing, dozens of causative genes have been identified to JS so far. Here, we investigated two male siblings with JS and uncovered a novel pathogenesis through combined methods. RESULTS: The siblings shared similar features of nystagmus, disorders of intellectual development, typical MTS, and abnormal morphology in fourth ventricle. Whole-exome sequencing (WES) and chromosome comparative genomic hybridization (CGH) were then performed on the proband. Strikingly, a maternal inherited nonsense variant (NM_025114.3: c.5953G>T [p.E1985*]) in CEP290 gene and a paternal inherited deletion in 12q21.32 including exons 1 to 10 of CEP290 gene were identified in the two affected siblings. We further confirmed the two variants by in vitro experiments: quantitative PCR and PCR sequencing. CONCLUSIONS: In this study, we first reported a novel causative mechanism of Joubert syndrome: a copy number variation (CNV) combined with a single-nucleotide variant in CEP290 gene, which can be helpful in the genetic diagnosis of this disease.

Topical Review: Optic Disc Pits and Associated Maculopathy.

SIGNIFICANCE: Although the treatment of optic disc pit maculopathy is controversial, this review concludes that the most successful current intervention is pars plana vitrectomy with peeling of the internal limiting membrane and induction of posterior vitreous detachment.Initially described in 1882, an optic disc pit is a rare defect of the optic nerve. This anomaly can result in sight-threatening retinopathy in the form of macular detachment and/or schisis. Outlined in this review of the literature are the incidence, clinical presentation, ancillary testing, pathogenesis, and management of optic disc pits and optic disc pit maculopathy.

Optic Disc Pit Maculopathy - Case Series, Clinical Approach, and Management.

PURPOSE: The purpose of this study was to analyze the diagnostic and therapeutic approach of five cases with optic disc pit (ODP) maculopathy. MATERIALS AND METHODS: This was a retrospective study of five patients diagnosed with ODP maculopathy. Four of these cases had unilateral involvement, whereas one case had bilateral findings. The medical notes of these individuals were reviewed in order to record the presenting symptoms, clinical signs, visual acuity (VA), imaging, management, and the final visual outcome on their last follow-up appointment. RESULTS: The first patient (53-year-old female) underwent a left pars plana vitrectomy (PPV) combined with inner retinal fenestration, endolaser, and perfluoropropane (C3F8) gas tamponade and her VA improved from 6/24 to 6/9 Snellen. A focal retinal laser treatment was carried out on our second patient leading to decrease of the subretinal fluid but had a poor visual outcome due to the underlying secondary glaucoma from iris melanoma treatment in the past. The third patient was an asymptomatic 7-year-old girl in which the maculopathy resolved spontaneously without any surgical intervention with a final VA of 6/5. The fourth and fifth patients were asymptomatic with good vision in both eyes and were, therefore, only monitored with follow-ups. CONCLUSION: ODP maculopathy remains a challenging clinical entity for a vitreoretinal surgeon. The current management for ODP maculopathy involves surgical procedures with PPV being a common treatment of choice. Spontaneous resolution of ODP maculopathy has also been reported. Our study highlights the contrasting management that can be adopted in the treatment of ODP maculopathy, and there is not one definite treatment for this condition.

Cutis marmorata telangiectatica congenita: a focus on its diagnosis, ophthalmic anomalies, and possible etiologic factors.

Purpose: Cutis marmorata telangiectatica congenita (CMTC) is a rare congenital disorder typified by localized or generalized cutaneous vascular anomalies, which dissipate over time. We review the diagnostic approach to CMTC and present a comprehensive examination of its ocular manifestations. Additionally, we offer recommendations for the ophthalmologic workup for patients with CMTC. Finally, we examine the possible causes of CMTC and summarize the current efforts to establish an etiologic mechanism for this disease.Methods: Thirty-three published cases of CMTC with ocular anomalies are examined in detail.Results: CMTC is diagnosed based on a specific set of congenital cutaneous symptoms, principally congenital reticular erythema that is unresponsive to local warming and absence of venectasia within the skin lesions. Ocular findings are not currently employed in this diagnostic process, likely due to an incomplete understanding into their presentation, frequency, and natural history. We show that the majority of ophthalmic manifestations are congenital, with glaucoma and posterior segment anomalies, consisting of retinal perfusion defects and vascular abnormalities, as the most frequently reported findings. Typical ophthalmic medical and surgical interventions appear to be effective for management of these CMTC-related pathology. Unfortunately, the etiology and pathophysiology of CMTC remains unknown, which obfuscates efforts to identify, examine, and initiate treatment in patients.Conclusions: While the ophthalmic community has traditionally viewed glaucoma as the classic ocular anomaly of CMTC, this dataset advocates for the prompt investigation of posterior segment abnormalities as well. However, our understanding of CMTC's ocular anomalies is complicated by a lack of reporting and/or incomplete (or nonexistent) ophthalmic examinations, and we strongly encourage comprehensive ophthalmic examinations for all CMTC patients at the time of diagnosis, followed by appropriate screening and surveillance throughout life. We believe these recommendations will spur additional data and disease insights that may be useful for future refinements to CMTC diagnostic algorithms.

Axenfeld-Rieger Anomaly and Neuropsychiatric Problems-More than Meets the Eye.

OBJECTIVE: The main purpose of this article is to demonstrate the co-occurrence of Axenfeld-Rieger anomaly and neuropsychiatric problems as clinical signs of genetically determined cerebral small vessel disease in two patients. CASE STUDY: We report on two adolescent individuals with ocular anterior segment dysgenesis (Axenfeld-Rieger anomaly) presenting with neuropsychiatric symptoms. Both patients underwent cerebral magnetic resonance imaging showing white matter T2-hyperintensities involving different brain regions, suspective of cerebral small vessel disease. Genetic analysis revealed pathogenic mutations in the FOXC1 gene (patient 1) and the COL4A1 gene (patient 2), respectively. CONCLUSION: We report on the co-occurrence of ocular anterior segment dysgenesis (Axenfeld-Rieger anomaly) and neuropsychiatric symptoms as clinical signs of genetically determined cerebral small vessel disease in two patients. In both patients, the cerebral lesions involved the frontotemporal regions, brain regions that control social behavior as well as executive and cognitive function, highlighting the fact that neuropsychiatric symptoms may be early clinical presentations of cerebral small vessel disease. We further provide a review of monogenic causes of pediatric cerebral small vessel disease, emphasizing the links to childhood-onset neuropsychiatric disease.

Case report: what gives the myopic tilted disc an oval appearance?

BACKGROUND: Myopic tilted disc, observed as an oval disc, has been alleged to be a funduscopic en-face manifestation of excessive optic nerve head (ONH) sloping or tilting. Here, we report the case of a myopic child showing a developing oval disc in fundus photos during axial elongation, but without progressive tilting in spectral-domain optical coherence tomography (SD-OCT) images. CASE PRESENTATION: By merging B-scan SD-OCT images of the ONH and macula, the curvature of the posterior pole, including both the fovea and ONH, was reconstructed and compared before and after 2 years of axial elongation. Despite the marked increase of disc ovality, the posterior polar curvature was rarely changed. The preponderance of optic disc change was induced by the shift of the temporal disc margin in the nasal direction. This shifting alone imitated an increase of tilt angle but one that was still far smaller than the required degree of tilt for ONH-tilt-based disc ovality. To clarify, we calculated the required extent of axial elongation to obtain a substantial degree of ONH tilt when considering the adjacency of the fovea and the ONH. Without a focal increase of posterior polar curvature, which is to say posterior staphyloma, such change is not possible until the axial length increases extraordinarily. CONCLUSION: The most prominent change in the development of myopic tilted disc, which change gives it an oval appearance and imitates a tilt when measured, is actually not a tilt but rather a shift of the temporal disc margin.

Associations between Attention-Deficit/Hyperactivity Disorder and Ocular Abnormalities in Children: A Population-based Study.

Purpose: Attention-deficit/hyperactivity disorder (ADHD) was reported to be associated with disturbances in the prefrontal circuitry and seems to be associated with dysfunctions of eye motility. This study aimed to explore associations between ADHD and ocular abnormalities, including amblyopia, hypermetropia, astigmatism, and heterotropia, using a large, nationwide population-based dataset in Taiwan.Methods: We retrieved our sample for this cross-sectional study from the Taiwan National Health Insurance Research Database. In total, 116,308 children with ADHD were selected as the study group and 116,308 randomly selected children without ADHD as the comparison group. We used conditional logistic regression analyses to examine the odds ratios (ORs) of amblyopia, hypermetropia, astigmatism, and heterotropia between children with and those without ADHD.Results: We found that children with ADHD had significantly higher prevalences of amblyopia (1.6% vs. 0.9%, p< .001), hypermetropia (2.4% vs. 1.3%, p < .001), astigmatism (0.2% vs. 0.1%, p < .001), and heterotropia (1.1% vs. 0.5%, p < .001) than children without ADHD. The ORs of amblyopia, hypermetropia, astigmatism and heterotropia for children with ADHD were 1.89 (95% confidence interval (CI) = 1.76 ~ 2.05), 1.82 (95% CI = 1.68 ~ 1.92), 1.73 (95% CI = 1.34 ~ 2.16), and 2.01 (95% CI = 1.82 ~ 2.21) compared to children without ADHD.Conclusions: The findings suggest that ADHD is associated with ocular abnormalities, including amblyopia, hypermetropia, astigmatism, and heterotropia.

Ocular abnormalities in a patient with congenital disorder of glycosylation type Ig.

Background: Congenital disorders of glycosylation (CDG) are a group of hereditary multisystem disorders characterized by hypoglycosylation of glycoproteins. CDG type I results in a defect in the assembly of lipid-linkedoligosaccharides or their transfer onto nascent glycoproteins. Ocular abnormalities are common in CDG, but there is no report of detailed ophthalmologic evaluation in patients with CDG type Ig in the literature.Materials and Methods: Retrospective chart review of a case of CDG type Ig with novel variant in the associated gene: ALG12.Results: In addition to typical systemic findings of CDG, our case was found to have exotropia, bilateralcataracts, and retinitis pigmentosa with extinguished electroretinography in photopic and scotopic conditions.Conclusions: We hope to extend the understanding of ALG12-related CDG type Ig with these ophthalmologic observations.

Long-term visual and anatomic outcomes following early surgery for persistent fetal vasculature: a single-center, 20-year review.

BACKGROUND: Persistent fetal vasculature (PFV) is a spectrum of congenital anomalies caused by complete or partial failure of the ocular fetal vasculature to regress. We report the visual and anatomic outcomes in a large cohort of patients who underwent early surgery for PFV. METHODS: We retrospectively reviewed the medical records of patients who underwent lensectomy and anterior or core vitrectomy for unilateral PFV without primary intraocular lens implantation through limbal or pars plana/plicata approach. Inclusion criteria were surgery prior to 7 months of age, with at least 12 months of follow-up. Eyes with severe posterior segment involvement and retinal detachment deemed beyond repair were excluded. RESULTS: A total of 58 patients met inclusion criteria. Mean age at surgery was 2.1 ± 1.5 months. Mean follow-up was 6.7 ± 4.2 years. At final follow-up, 19 eyes (33%) had visual acuity better than 1.0 logMAR. Thirty-three eyes (57%) developed 1 or more postoperative adverse events: glaucoma in 21 (36%) and retinal detachment in 11 (19%), 8 of which occurred in eyes that had pars plana or pars plicata incisions (P = 0.002). In patients with limbal incisions, 17 of 40 (43%) achieved a visual acuity better than 1.0 logMAR, compared with 2 of 18 patients (11%) with a pars plana/pars plicata incision (P = 0.03). CONCLUSIONS: In our study cohort, early surgery for PFV achieved functional visual acuity in about one-third of patients. Limbal approach to surgery may result in better visual acuity and anatomic results.

A case of PHACE syndrome with growth hormone deficiency and abnormal thyroid functions.

Background PHACE syndrome is a rare vascular neurocutaneous disorder characterized by posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies and eye anomalies. Growth hormone deficiency (GHD) has been infrequently described. Case presentation We report a girl with PHACE syndrome. Endocrine abnormalities including abnormal thyroid functions and GHD have recently been described in similar cases. Conclusions This case suggests the necessity to screen pituitary functions in all patients with PHACE syndrome with abnormal hypothalamus and pituitary (HP) anatomy. Likewise, growth parameters and thyroid function test (TFT) should be monitored in all patients with PHACE syndrome at regular intervals.

Endocrine manifestations of PHACE syndrome.

PHACE syndrome is an uncommon disorder of posterior fossa anomalies, cervicofacial infantile hemangiomas, arterial anomalies, cardiac defects, eye anomalies, and midline/ventral defects. Endocrine abnormalities including hypopituitarism and ectopic thyroid were rarely described. In this article we review occurrence, onset, presenting symptoms, hormonal treatments and outcomes of all endocrine abnormalities in PHACE syndrome. Eleven of 20 (55%) had hypothalamic-pituitary dysfunction and 10 of 20 (50%) had thyroid dysgenesis. A thorough understanding of the endocrine manifestations is important for clinicians to early identify endocrine involvement in PHACE and develop plans for monitoring and treatment of its complications.