Phenotypic spectrum of FGF10-related disorders: a systematic review.

FGF10, as an FGFR2b-specific ligand, plays a crucial role during cell proliferation, multi-organ development, and tissue injury repair. The developmental importance of FGF10 has been emphasized by the identification of FGF10 abnormalities in human congenital disorders affecting different organs and systems. Single-nucleotide variants in FGF10 or FGF10-involving copy-number variant deletions have been reported in families with lacrimo-auriculo-dento-digital syndrome, aplasia of the lacrimal and salivary glands, or lethal lung developmental disorders. Abnormalities involving FGF10 have also been implicated in cleft lip and palate, myopia, or congenital heart disease. However, the exact developmental role of FGF10 and large phenotypic heterogeneity associated with FGF10 disruption remain incompletely understood. Here, we review human and animal studies and summarize the data on FGF10 mechanism of action, expression, multi-organ function, as well as its variants and their usefulness for clinicians and researchers.

Congenital alacrima.

The congenital absence of tear production or alacrima is a distinctively unusual clinical sign that harbors a wide variety of etiologies. While alacrima can be only isolated to the lacrimal system, it is more often associated with progressive multisystem involvement from underlying genetic disorders. Recognizing the subtle ocular signs in these diseases will promote a timely diagnosis and management before potential life-threatening consequences occur. Hence, the current article will review the ophthalmological findings, systemic manifestations, genetic associations, and differential diagnosis of congenital alacrima.

Update on the Long-Term Outcomes Following the Management of Incomplete Punctal Canalization.

PURPOSE: To study the clinical profile, associated lacrimal disorders, and long-term outcomes following a membranotomy, in patients with incomplete punctal canalization (IPC). METHODS: Retrospective interventional study was performed of all the patients diagnosed with IPC during the study period over 5 years from January 2015 to December 2020. The diagnosis of IPC was made based on the earlier published guidelines. A combination of rapid and slow taper Nettleship's punctal dilators were used for an effective membranotomy, followed by further assessment of the lacrimal drainage passage. Appropriate interventions for associated lacrimal disorders were performed. Data collected on chart reviews include demographics, clinical presentation, laterality, type of IPC, associated lacrimal anomalies, management modalities, and long-term outcomes. RESULTS: Ninety-eight puncta of 62 eyes of 46 patients with IPC were examined in the clinic. Incomplete punctal canalization-external membrane variant was seen in 62% (61/98) and internal membrane variant in 38% (37/98). Seventy-eight puncta (78/98, 79.5%) in 39 patients underwent membranotomy using Nettleship's punctal dilator. Associated lacrimal drainage pathway deformities were seen in 31% of patients (12/39). Three puncta had mini-monoka insertion for associated canalicular stenosis and canalicular obstruction. Five patients with associated congenital nasolacrimal duct obstruction underwent probing, of which 3 patients needed dacryocystorhinostomy for complex congenital nasolacrimal duct obstruction. Associated punctal agenesis was noted in 3 patients involving the other punctum of the same eye. Canalicular wall hypoplasia involving 3 walls of the canaliculus was seen in 1 patient. At a mean follow up of 28 months, the anatomical and functional outcomes were noted in 100% and 97.4%, respectively. CONCLUSIONS: The long-term outcomes of membranotomy for IPC are excellent. Associated congenital lacrimal drainage anomalies are common with IPC.

Agenesia unilateral congénita de glándula lagrimal con sustitución por lipoma. Un caso raro de alacrimia congénita unilateral / Congenital unilateral absence of the lacrimal gland combined with lipoma. A rare case of unilateral congenital alacrima

El propósito de este artículo es describir un caso de agenesia lagrimal congénita unilateral en una niña de 7 años con síntomas oculares, ausencia de secreción lagrimal y una tumoración conjuntival en el ángulo superoexterno del ojo derecho. La agudeza visual era de 20/20 en ambos ojos. El ojo derecho presentaba secreción mucosa, erosiones y filamentos corneales. La anamnesis, la exploración física y las pruebas analíticas descartaron enfermedades sistémicas asociadas a la alacrimia congénita, así como enfermedades reumatológicas, inmunológicas o infecciosas. La resonancia nuclear magnética con diversas técnicas de supresión grasa mostró la ausencia de glándula lagrimal derecha y la presencia de una tumoración compatible con lipoma. Este caso, para nuestro conocimiento, representa la primera comunicación de una agenesia unilateral de glándula lagrimal combinada con un lipoma

The purpose of this report is to describe a case of a unilateral congenital absence of the lacrimal gland in a 7-year-old girl with ocular symptoms, no tear production and a conjunctival tumour at the supero-external angle of the right eye. The visual acuity was 20/20 in both the eyes. The right eye showed mucous secretion, corneal erosions and filaments. Anamnesis, physical examination and clinical tests ruled out systemic diseases associated with congenital alacrima, as well as rheumatic, immunological and infectious diseases. Nuclear magnetic resonance, with various fat suppression techniques, demonstrated the absence of the right lacrimal gland and the presence of a tumour compatible with lipoma. This case, to our knowledge, is the first report of unilateral absence of the lacrimal gland combined with lipoma

Identification of KRAS mutation in a patient with linear nevus sebaceous syndrome: a case report.

BACKGROUND: Linear nevus sebaceous syndrome (LNSS) is a rare genetic disease characterized by large linear sebaceous nevus typically on the face, scalp, or neck. LNSS could be accompanied by multisystem disorders including the central nervous system. Herein, we report gene mutational profile via whole exome sequencing of both lesional and non-lesional skin samples in a LNSS patient. CASE PRESENTATION: A 17-year-old girl presented with multisystem abnormalities, including large skin lesions, ocular disorders, abnormal bone development and neurological symptoms. A diagnosis of LNSS was established based on clinical manifestations, histopathological and imaging findings. The skin lesions were resected and no recurrence was noted at the time of drafting this report. Whole exome sequencing of genomic DNA revealed the following 3 mutations in the lesions of the index patient: KRAS (c.35G > A, p.G12D), PRKRIR (c.A1674T, p.R558S), and RRP7A (c. C670T, p.R224W), but no mutation was found in the healthy skin and peripheral blood sample of the index patient, or in the blood samples of her parents and sibling. PCR-mediated Sanger sequencing of DNA derived from lesional skin sample of the index patient verified KRAS mutation, but not PRKRIR (c.A1674T, p.R558S) and RRP7A (c. C670T, p.R224W). None of the 3 mutations was found in Sanger sequencing in skin lesions of 60 other cases of nevus sebaceous patients. CONCLUSIONS: Our findings show the relevance of KRAS mutation to LNSS, providing new clues in understanding related genetic heterogeneity which could aid genetic counselling for LNSS patients.

Malformation of Tear Ducts Underlies the Epiphora and Precocious Eyelid Opening in Prickle 1 Mutant Mice: Genetic Implications for Tear Duct Genesis.

Purpose: Obstruction of the tear drainage causes a range of ocular surface disorders. Hitherto, the genetics of tear duct development and obstruction has been scarcely explored, and related animal models are lacking. This study aims to study the potential role of the Wnt/PCP pathway mediated by Prickle 1 in tear duct development and diseases. Methods: A severe hypomorphic Prickle 1 mutant was generated. Histology and immunohistochemistry were performed to compare wild type, Prickle 1 hypomorphic, and null mutant tear ducts. In situ hybridization was conducted to identify the signaling components in the developing tear ducts. Three-dimensional (3D) reconstruction was used to detect the human embryonic tear duct. Results: Here, we report that a severe Prickle 1 hypomorph mouse line exhibited epiphora. This phenotype was due to the blockage of the tear drainage by incompletely formed nasolacrimal duct (NLD) and lacrimal canaliculi (LC), which also causes precocious eyelid opening. We observed a dose-dependent requirement of Prickle 1 for tear duct outgrowth. An investigation of the expression of Wnt/PCP core genes demonstrated a subset of PCP signaling components expressed in the developing tear duct. Furthermore, Prickle 1 is not required for the expression of Fgfr2/Fgf10 and p63 genes, which are associated with the NLD and LC hypoplasia in humans. Last, we showed that Prickle 1 expression in the developing tear drainage system is conserved between mice and humans. Conclusions: The study suggests that malformed tear ducts caused by disruption of Prickle 1 underlies the epiphora and precocious eyelid opening.

Lacrimal drainage system anomalies in microphthalmia anophthalmia coloboma complex.

Purpose: To study the prevalence and types of lacrimal drainage system (LDS) anomalies inchildren with congenital microphthalmia anophthalmia coloboma (MAC) complex.Methods: This is a prospective, consecutive, non-comparative, case series of LDS anomalies in 31 children presenting with MAC complex. Previously untreated children with MAC complex, enrolled for socket surface and volume expansion during the study period from January 2017 to April 2018 were included.Results: Thirty-one patients with MAC complex were evaluated for LDS anomalies. Incidence of LDS anomalies in children presenting with MAC complex was 68% (42 of 62 lacrimal systems evaluated). Mean age of the patients at the time of examination under anaesthesia was 27 ± 25 (median 15 months, range 3-108 months). Proximal bicanalicular block (BCB) was the commonest LDS anomaly, noted in 15 (48%) cases. In patients with unilateral ocular disease (n = 20), LDS was affected in 14 (70%) patients and in 9 (45%) patients ipsilateral side LDS was affected. In patients with bilateral ocular disease (n = 11), LDS was affected in 7 (64%) patients. Three patients with unilateral anophthalmos (25%) had an ipsilateral upper canalicular block and contralateral nasolacrimal duct obstruction, of which one patient had a single canalicular wall hypoplasia along with CNLDO. No patient had punctal anomalies.Conclusions: LDS anomalies are seen in nearly two-thirds (68%) of children with MAC complex. The lacrimal drainage system anomaly is not limited to the side of the MAC complex. Commonest LDS anomaly is proximal bicanalicular blocks while punctal anomalies are unusual.

Congenital canaliculops with punctal agenesis: is there a possibility to establish patency?

Canaliculops is a non-inflammatory dilatation of the canaliculus which can be secondary to trauma, punctal agenesis, herpetic infections or chronic drug use. This condition can affect either canaliculi and has shown female preponderance. Treatment described so far has consisted of cyst marsupialization with no literature on the post-operative epiphora in these cases. We describe two cases of canaliculops with punctal agenesis where we have tried to establish lacrimal patency.

Ocular findings in Fabry disease in Colombian patients / Manifestaciones oculares de la enfermedad de Fabry en pacientes colombianos

Fabry disease is a rare X-linked disorder caused by an alpha-galactosidase enzyme deficiency, which leads to a progressive lysosomal glycosphingolipids accumulation, mainly globotriaosylceramide, in multiple organism tissues including the eye. This case series describes the first ophthalmological Colombian report of Fabry disease highlighting the importance of ocular signs as markers of the disease, useful in diagnosis and treatment to avoid long-term complications that lead to a morbi-mortality increment. We describe five cases of Fabry disease from Bogotá, Colombia, including a complete clinical history, ophthalmologic, optometric examination, and photographs. We found that all patients had refractive defects and that in all cases corneal verticillata pattern was found. Four patients presented with posterior capsule lens brown-beige deposits and four patients had conjunctival and retinal tortuous vessels. A complete ophthalmologic examination is important for prompt diagnosis, which is key to starting a multidisciplinary treatment and reducing morbi-mortality.

La enfermedad de Fabry es un raro trastorno ligado al cromosoma X causado por deficiencia de la enzima alfa-galactosidasa y la consiguiente y progresiva acumulación lisosómica de glucoesfingolípidos, especialmente la globotriaosilceramida, en múltiples tejidos del organismo, incluido el ojo. En este reporte se presenta la primera serie de casos de manifestaciones oculares de la enfermedad de Fabry en Colombia, resaltando la importancia de los signos oculares como ayuda para el diagnóstico temprano. Se presentan cinco casos de la enfermedad en Bogotá y se da cuenta de las historias clínicas y los exámenes oftalmológicos y de optometría, y se incluyen fotografías. En todos los pacientes se hallaron errores de refracción y se evidenció el patrón de córnea verticillata. Cuatro pacientes presentaban depósitos de color café y castaño claro en la cápsula posterior del cristalino, y cuatro tenían tortuosidad vascular conjuntival y retiniana. El examen oftalmológico completo es importante para hacer un diagnóstico oportuno con el fin de iniciar el tratamiento multidisciplinario y reducir la morbimortalidad.

Ocular findings in Fabry disease in Colombian patients / Manifestaciones oculares de la enfermedad de Fabry en pacientes colombianos

ABSTRACT Fabry disease is a rare X-linked disorder caused by an alpha-galactosidase enzyme deficiency, which leads to a progressive lysosomal glycosphingolipids accumulation, mainly globotriaosylceramide, in multiple organism tissues including the eye. This case series describes the first ophthalmological Colombian report of Fabry disease highlighting the importance of ocular signs as markers of the disease, useful in diagnosis and treatment to avoid long-term complications that lead to a morbi-mortality increment. We describe five cases of Fabry disease from Bogotá, Colombia, including a complete clinical history, ophthalmologic, optometric examination, and photographs. We found that all patients had refractive defects and that in all cases corneal verticillata pattern was found. Four patients presented with posterior capsule lens brown-beige deposits and four patients had conjunctival and retinal tortuous vessels. A complete ophthalmologic examination is important for prompt diagnosis, which is key to starting a multidisciplinary treatment and reducing morbi-mortality.

RESUMEN La enfermedad de Fabry es un raro trastorno ligado al cromosoma X causado por deficiencia de la enzima alfa-galactosidasa y la consiguiente y progresiva acumulación lisosómica de glucoesfingolípidos, especialmente la globotriaosilceramida, en múltiples tejidos del organismo, incluido el ojo. En este reporte se presenta la primera serie de casos de manifestaciones oculares de la enfermedad de Fabry en Colombia, resaltando la importancia de los signos oculares como ayuda para el diagnóstico temprano. Se presentan cinco casos de la enfermedad en Bogotá y se da cuenta de las historias clínicas y los exámenes oftalmológicos y de optometría, y se incluyen fotografías. En todos los pacientes se hallaron errores de refracción y se evidenció el patrón de córnea verticillata. Cuatro pacientes presentaban depósitos de color café y castaño claro en la cápsula posterior del cristalino, y cuatro tenían tortuosidad vascular conjuntival y retiniana. El examen oftalmológico completo es importante para hacer un diagnóstico oportuno con el fin de iniciar el tratamiento multidisciplinario y reducir la morbimortalidad.

Punctal agenesis: Embryology, presentation, management modalities and outcomes.

Punctal agenesis is defined as the absence of the punctum occurring secondary to a failure of embryogenesis. This review synthesizes existing data on the embryology, anatomy, clinical presentation, symptomatology, management options and treatment outcomes of punctal agenesis. A foundational knowledge of the underlying embryologic and anatomical abnormalities is fundamental to understanding its clinical presentation and assists in choosing an appropriate management strategy. Existing outcomes data is generally favorable and suggests management with a step-wise approach can alleviate symptoms in patients across a spectrum of disease.

Characterizing Congenital Double Punctum Anomalies: Clinical, Endoscopic, and Imaging Findings.

PURPOSE: To characterize the anatomical anomaly of congenital double puncta, identify factors contributing to epiphora and its treatment. METHODS: Retrospective review of patients presenting with epiphora and a double lacrimal punctum over a 6-month period. RESULTS: Five consecutive patients (3 female) were identified. The median age was 50 years (range 34-76). Investigations included punctum optical coherence tomography, dacryocystography, and canalicular endoscopy. The medial punctum was more morphologically abnormal when compared with healthy puncta, with optical coherence tomography showing no vertical canalicular component in 80% (4/5) of patients, and a more superficial than usual horizontal canaliculus in 80% (4/5). Dacryocystography and canalicular endoscopy showed the junction of the 2 inferior canaliculi, which was very proximal in 1, mid canalicular in 2, and at the level of the common canaliculus in 2. In 1 patient, the only abnormality identified was the double lower punctum, with a high tear meniscus and delayed fluorescence dye disappearance test. They underwent endonasal dacryocystorhinostomy with improvement of epiphora. In the other 4 patients, causes of epiphora were nasolacrimal duct stenosis with mucocoele, punctal stenosis, common canalicular stenosis with nasolacrimal duct stenosis, upper canaliculitis, and blepharitis. Their treatments included endonasal dacryocystorhinostomy, punctoplasty, canaliculotomy, and blepharitis treatment. All had improvement of epiphora following treatment. CONCLUSIONS: These findings suggest that the underlying canalicular anomalies are varied and that the clinical manifestation is also heterogenous. Optical coherence tomography imaging suggests that the medial of the 2 puncta is the more morphologically abnormal one, with dacryocystography and canalicular endoscopy demonstrating different accessory canaliculi lengths.Double puncta coexist with a range of other nasolacrimal pathologies. OCT suggests that the medial of the 2 double puncta is the abnormal one, with DCG and endoscopy demonstrating a range of accessory canaliculus lengths.

A rare case of atypical pleomorphic adenoma arising from periocular ectopic lacrimal gland.

PURPOSE: To describe features of atypical pleomorphic adenoma, a rare clinical entity, particularly when found in ectopic periocular lacrimal gland tissue. METHODS: Case report of biopsy-confirmed periocular atypical pleomorphic adenoma. RESULTS: A 35-year-old female presented with a unique orbital lesion found to be ectopic lacrimal gland demonstrating atypical pleomorphic adenoma on formal histopathologic review. Pleomorphic adenoma is pathologically characterized as an epithelial lesion intermixed with mesenchymal elements. It is further classified as atypical with the presence of features such as hypercellularity, regions of necrosis or hyalinization, cellular dysplasia, capsular violation, and malignant characteristics without frank local extension or distant metastases. CONCLUSIONS: Due to its rarity, the natural history and prognosis of atypical pleomorphic adenoma is unclear. Physicians need to recognize this entity, and complete surgical excision with strict follow-up regimens are likely warranted.

Selection of surgical intervention for congenital dacryocystocele.

PURPOSE:: To evaluate the surgical intervention and its effect on congenital dacryocystocele. METHODS:: A total of 531 children with congenital dacryocystocele admitted to the Department of Ophthalmology of Beijing Children's Hospital, Shanghai Aier Eye Hospital, Nanjing Aier Eye Hospital, and the First Affiliated Hospital of Jinzhou Medical University between January 2007 and January 2017 were retrospectively analyzed. RESULTS:: A total of 531 patients were followed up for 3-24 months, with an average of 13.3 months. No serious intraoperative complications (such as bleeding and tissue damage) and postoperative complications (bleeding, infection, and hole atresia) were found. We classified the outcomes into three categories based on the signs (overflowing tears and empyema) and objective routine follow-up by endoscopy. Cure indicated that mass, overflow of tears, and breathing difficulties disappeared, and 81.5% cases (433/531) were postoperatively cured. Improvement indicated disappearance of mass, overflow empyema, and the presence of residual tears (due to trocar and tears puncture), and 18.5% cases (98/531) were postoperatively improved. Unhealed indicated overflowing pus and tears, and 0% cases did not heal after surgery. CONCLUSIONS:: Nasal endoscopic surgery is relatively safe, with high success rate for treatment of congenital dacryocystocele. Systematic training is required to promote the application of nasal endoscopy, so that more ophthalmologists can learn this technique.

Dacryoendoscopy-assisted nasal endoscopic marsupialization for congenital dacryocystocele.

OBJECTIVE: To examine the surgical outcome of dacryoendoscopy-assisted nasal endoscopic marsupialization for congenital dacryocystocele. METHODS: This is a retrospective, observational study that included 7 sides of 6 patients with congenital dacryocystocele. The surgical indication in 5 of the patients was acute dacryocystitis while one of the patients had no spontaneous resolution after long-term observation. Dacryoendoscopy was used for visualisation of the lacrimal cavity, direct probing of the obstruction at the common canaliculus, and localisation of a deflated intranasal cyst after an initial incision of the cyst. Surgical success was defined when the following postoperative conditions were satisfied: no epiphora, normal tear meniscus height, and complete clearance of the dye 5 min after instilling a drop of 2% fluorescein solution into the inferior conjunctional fornix. RESULTS: Out of 6 patients, 2 patients were noted to have membranous common canalicular obstruction. Postoperative follow-up ranged from 11 days to 3 months. Surgical success was achieved in all patients without any complication. CONCLUSIONS: Dacryoendoscopy-assisted nasal endoscopic marsupialization is an effective surgical management for congenital dacryocystocele.