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Objective: To assess clinical factors leading to recurrent retinal detachment (RD) and characteristics of recurrence in patients with Stickler Syndrome. Methods: Retrospective case series study of patients with clinical diagnosis of Stickler Syndrome who underwent rhegmatogenous RD repair. Recurrent RD after initial surgery was categorized as "early" if the recurrence was within 1 year or "late" if greater than 1 year. Results: Thirty eyes from 22 patients underwent rhegmatogenous RD repair. For initial repair, 13 eyes underwent pars plana vitrectomy combined with scleral buckling (PPV/SB), 16 eyes underwent primary scleral buckling (SB), and 1 eye underwent pneumatic retinopexy (PnR). Recurrent RD occurred in 6 (46%) PPV/SB eyes (5 early and 1 late), 10 (63%) SB eyes (3 early and 7 late), and 0 (0%) PnR eyes (p = 0.61). PPV/SB was preferred for eyes presenting with total detachment (82%), giant retinal tears (100%), and proliferative vitreoretinopathy (PVR) (80%). For eyes with early recurrent RD, 6 (75%) developed PVR leading to recurrence. For eyes with late recurrent RD, 7 (87.5%) developed a new retinal break leading to recurrence, including 4 with a break posterior to the buckle indentation apex. At last follow-up, median LogMAR visual acuity was 0.68 for eyes with recurrent RD compared to 0.29 for eyes without recurrence (p = 0.27). Conclusions: Early recurrent RD was mostly caused by PVR, while late recurrent RD was mostly due to new retinal breaks. Eyes with seemingly uncomplicated rhegmatogenous RD repair with primary SB remained at high risk for late re-detachment.
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Long chain 3-hydroxyacyl-CoA dehydrogenase (LCHADD) is the only fatty acid oxidation disorder to develop a progressive chorioretinopathy resulting in vision loss; newborn screening (NBS) for this disorder began in the United States around 2004. We compared visual outcomes among 40 participants with LCHADD or trifunctional protein deficiency diagnosed symptomatically to those who were diagnosed via NBS or a family history. Participants completed ophthalmologic testing including measures of visual acuity, electroretinograms (ERG), fundal imaging, contrast sensitivity, and visual fields. Records were reviewed to document medical and treatment history. Twelve participants presented symptomatically with hypoglycemia, failure to thrive, liver dysfunction, cardiac arrest, or rhabdomyolysis. Twenty eight were diagnosed by NBS or due to a family history of LCHADD. Participants diagnosed symptomatically were older but had similar percent males and genotypes as those diagnosed by NBS. Treatment consisted of fasting avoidance, dietary long-chain fat restriction, MCT, C7, and/or carnitine supplementation. Visual acuity, rod- and cone-driven amplitudes on ERG, contrast sensitivity scores, and visual fields were all significantly worse among participants diagnosed symptomatically compared to NBS. In mixed-effects models, both age and presentation (symptomatic vs. NBS) were significant independent factors associated with visual outcomes. This suggests that visual outcomes were improved by NBS, but there was still lower visual function with advancing age in both groups. Early diagnosis and treatment by NBS is associated with improved visual outcomes and retinal function compared to participants who presented symptomatically. Despite the impact of early intervention, chorioretinopathy was greater with advancing age, highlighting the need for novel treatments.
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Diagnóstico Precoz , Errores Innatos del Metabolismo Lipídico , Proteína Trifuncional Mitocondrial , Tamizaje Neonatal , Enfermedades de la Retina , Agudeza Visual , Humanos , Masculino , Femenino , Recién Nacido , Errores Innatos del Metabolismo Lipídico/diagnóstico , Errores Innatos del Metabolismo Lipídico/genética , Errores Innatos del Metabolismo Lipídico/terapia , Niño , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/genética , Proteína Trifuncional Mitocondrial/deficiencia , Adulto , Lactante , Preescolar , Adolescente , Enfermedades Musculares/diagnóstico , Enfermedades Musculares/genética , Adulto Joven , Carnitina/análogos & derivados , Carnitina/uso terapéutico , Electrorretinografía , Miopatías Mitocondriales/diagnóstico , Miopatías Mitocondriales/genética , 3-Hidroxiacil-CoA Deshidrogenasas/deficiencia , 3-Hidroxiacil-CoA Deshidrogenasas/genética , Cardiomiopatías/diagnóstico , Cardiomiopatías/genética , Resultado del Tratamiento , Rabdomiólisis/diagnóstico , Rabdomiólisis/genética , Enfermedades del Sistema NerviosoRESUMEN
PURPOSE: To evaluate the imaging and clinical features of unusual calcified lesions seen in the fundus of patients with mosaic RASopathy. DESIGN: Single-center retrospective observational study. SUBJECTS: Ten eyes with calcified fundus lesions in 7 patients with mosaic RASopathy. METHODS: The lesions were evaluated with fundus photography, oral fundus fluorescein angiography, B-scan ultrasonography, magnetic resonance imaging (MRI), and computed tomography (CT) scan where available. MAIN OUTCOME MEASURES: The imaging characteristics of calcified fundus lesions were assessed. RESULTS: We found 7 patients with mosaic RASopathies, 5 men and 2 women (3 with linear sebaceous nevus syndrome, 3 with oculoectodermal syndrome, and 1 with encephalocraniocutaneous lipomatosis) with molecular confirmation in 5 cases, all 5 having KRAS-pathogenic variants. Calcified fundus lesions were identified in 10 eyes (bilateral in 3 patients), appearing as slightly elevated, creamy-yellow lesions around or adjacent to the optic nerve, extending supero-nasally; all but 2 of these lesions involved both the choroid and sclera, with 2 of them only involving the sclera at the time of examination. One case developed a choroidal neovascular membrane necessitating intravitreal bevacizumab injections. All 7 patients had B-scan ultrasonography, and the lesion appeared as a hyperechogenic area with an acoustic shadow posteriorly despite reduced gain. Five patients had MRI, and where fundus lesions were present, there was a focal defect in the sclero-choroidal layer. Four patients had a CT scan, and all 4 showed calcifications affecting both the posteromedial sclero-choroid and adjacent medial rectus muscle. Two of these patients had normal eye movements, 1 had a unilateral fixed adducted eye and a vestigial fibrous medial rectus muscle seen in imaging and intraoperatively, and the fourth had marked exotropia with a right gaze deficit affecting both eyes. CONCLUSIONS: We propose that the lesions seen in this cohort are calcified sclero-choroidal choristomas and should be suspected in mosaic RASopathies when creamy-yellow lesions are seen in the fundus. If identified, the possibility of choroidal neovascularization should be considered during follow-up. In all cases where a CT scan was performed, a novel sign of sclero-muscular calcification involving the medial rectus muscle was seen. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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Calcinosis , Coristoma , Angiografía con Fluoresceína , Imagen por Resonancia Magnética , Enfermedades de la Esclerótica , Humanos , Masculino , Femenino , Estudios Retrospectivos , Calcinosis/diagnóstico , Calcinosis/diagnóstico por imagen , Angiografía con Fluoresceína/métodos , Imagen por Resonancia Magnética/métodos , Enfermedades de la Esclerótica/diagnóstico , Coristoma/diagnóstico , Adulto , Síndromes Neurocutáneos/diagnóstico , Adolescente , Niño , Fondo de Ojo , Tomografía Computarizada por Rayos X , Adulto Joven , Nevo Sebáceo de Jadassohn/diagnóstico , Enfermedades de la Coroides/diagnóstico , Coroides/patología , Coroides/diagnóstico por imagen , Displasia Ectodérmica/diagnóstico , Displasia Ectodérmica/genética , Displasia Ectodérmica/complicaciones , Preescolar , Lipomatosis/diagnóstico , OftalmopatíasRESUMEN
OBJECTIVE: To develop an updated staging system for long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency (LCHADD) chorioretinopathy based on contemporary multimodal imaging and electrophysiology. METHODS: We evaluated forty cases of patients with genetically confirmed LCHADD or trifunctional protein deficiency (TFPD) enrolled in a prospective natural history study. Wide-field fundus photographs, fundus autofluorescence (FAF), optical coherence tomography (OCT), and full-field electroretinogram (ffERG) were reviewed and graded for severity. RESULTS: Two independent experts first graded fundus photos and electrophysiology to classify the stage of chorioretinopathy based upon an existing published system. With newer imaging modalities and improved electrophysiology, many patients did not fit cleanly into a single traditional staging group. Therefore, we developed a novel staging system that better delineated the progression of LCHADD retinopathy. We maintained the four previous delineated stages but created substages A and B in stages 2 to 3 to achieve better differentiation. DISCUSSION: Previous staging systems of LCHADD chorioretinopathy relied on only on the assessment of standard 30 to 45-degree fundus photographs, visual acuity, fluorescein angiography (FA), and ffERG. Advances in recordings of ffERG and multimodal imaging with wider fields of view, allow better assessment of retinal changes. Following these advanced assessments, seven patients did not fit neatly into the original classification system and were therefore recategorized under the new proposed system. CONCLUSION: The new proposed staging system improves the classification of LCHADD chorioretinopathy, with the potential to lead to a deeper understanding of the disease's progression and serve as a more reliable reference point for future therapeutic research.
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Cardiomiopatías , Enfermedades de la Coroides , Errores Innatos del Metabolismo Lipídico , Miopatías Mitocondriales , Proteína Trifuncional Mitocondrial/deficiencia , Enfermedades del Sistema Nervioso , Enfermedades de la Retina , Rabdomiólisis , Humanos , Estudios Prospectivos , Enfermedades de la Retina/diagnóstico , Retina/metabolismo , Tomografía de Coherencia Óptica , Angiografía con Fluoresceína/métodosRESUMEN
PURPOSE: The aim of this study is to describe the variable phenotype of congenital corneal opacities occurring in patients with biallelic CYP1B1 pathogenic variants. METHODS: A retrospective chart review was conducted to identify patients with congenital corneal opacities and CYP1B1 pathogenic variants seen at UPMC Children's Hospital of Pittsburgh. Ophthalmic examination, high-frequency ultrasound, anterior segment optical coherence tomography, histopathologic images, and details of genetic testing were reviewed. RESULTS: Three children were identified. All presented with raised intraocular pressure. Two patients showed bilateral limbus-to-limbus avascular corneal opacification that did not resolve with intraocular pressure control; 1 showed unilateral avascular corneal opacity with a crescent of clear cornea, iridocorneal adhesions, iridolenticular adhesions, and classical features of congenital glaucoma in the fellow eye (enlarged corneal diameter, Haab striae, and clearing of the corneal clouding with appropriate intraocular pressure control). The first 2 patients were visually rehabilitated with penetrating keratoplasty. Histopathology revealed distinct features: a variably keratinized epithelium; a thick but discontinuous Bowman-like layer with areas of disruption and abnormal cellularity; Descemet membrane, when observed, showed reduced endothelial cells; and no pathological changes of Haab striae were identified. Two patients had compound heterozygous pathogenic variants in CYP1B1 causing premature stop codons, whereas 1 was homozygous for a pathogenic missense variant. CONCLUSIONS: Congenital corneal opacities seen in biallelic CYP1B1 pathogenic variants have a variable phenotype. One is that commonly termed as Peters anomaly type 1 (with iridocorneal adhesions, with or without iridolenticular adhesions) and the other is a limbus-to-limbus opacity, termed CYP1B1 cytopathy. Clinicians should be aware of this phenotypic variability.
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Enfermedades de la Córnea , Opacidad de la Córnea , Niño , Humanos , Estudios Retrospectivos , Células Endoteliales , Opacidad de la Córnea/diagnóstico , Opacidad de la Córnea/genética , Opacidad de la Córnea/cirugía , Enfermedades de la Córnea/diagnóstico , Enfermedades de la Córnea/genética , Fenotipo , Variación Biológica Poblacional , Citocromo P-450 CYP1B1/genéticaRESUMEN
OBJECTIVE: To describe the first paediatric case series of Thygesons' superficial punctate keratitis (TSPK) with management outcomes. METHODS: A retrospective chart review was done for all children either diagnosed at initial presentation or referred with TSPK from 01/2012 to 08/2021 at a tertiary children's hospital. Records were assessed for signs, symptoms, diagnosis, steroid and cyclosporine 0.05% use. The main outcome measures were visual acuity, treatment response and total steroid exposure. RESULTS: Fifteen children (7 females), mean age at presentation 8 ± 4 years were included. All had bilateral disease and a BCVA of >20/40 in the better eye. All patients received topical fluorometholone 0.1%, (FML) initially. 80% had a good response to FML. Corneal scraping was done to exclude infectious causes in four cases due to poor initial response or clinical suspicion. All 4 needed EUA for scraping and anterior segment OCT, after which 2 had molecularly confirmed TGFBI-related stromal dystrophy. For the rest, slow steroid taper was done every 4-6 weeks and recurrences were treated by increasing steroid frequency. Cyclosporine 0.05% was started in nine patients (69%), 8 ± 6 months after initial presentation. The decrease in total steroid exposure per week after starting cyclosporine was statistically significant (p < 0.05). CONCLUSION: Children with TSPK respond quickly to steroids, however, recurrences are common, necessitating a slow taper. Non-response to steroid needs careful reconsideration of the diagnosis and may necessitate the use of an EUA. Using cyclosporine 0.05% reduces the total steroid exposure in TSPK.
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Córnea , Queratitis , Femenino , Humanos , Niño , Preescolar , Fluorometolona/uso terapéutico , Estudios Retrospectivos , Queratitis/diagnóstico , Queratitis/tratamiento farmacológico , Queratitis/etiología , Ciclosporina/uso terapéuticoRESUMEN
PURPOSE: The aim of this study was to report a case of corneal plana-like phenotype with bilateral peripheral scleralization associated with a PITX2 pathogenic variant. METHODS: Clinical findings were obtained by ophthalmologic examination. Molecular diagnosis was performed by whole-exome sequencing in the patient and his parents. RESULTS: A 12-month-old male patient present with bilateral peripheral corneal scleralization, corneal plana-like phenotype, and iris hypoplasia. The genetic analysis revealed a de novo PITX2 pathogenic variant (c.323G>A, p.R108H). CONCLUSIONS: PITX2 c.323G>A (p.R108H) can be associated with a unique corneal plana-like phenotype with peripheral scleralization, and thus, PITX2 should be targeted in genetic testing of this specific phenotype.
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Enfermedades de la Córnea , Proteínas de Homeodominio , Humanos , Masculino , Enfermedades de la Córnea/patología , Proteínas de Homeodominio/genética , Mutación , Linaje , Fenotipo , Factores de Transcripción/genética , Lactante , Proteína del Homeodomínio PITX2RESUMEN
PURPOSE: The purpose of this study was to describe the deep phenotype of congenital corneal opacities (CCO) in patients with 22q11.2 deletion syndrome (22q11.2 DS) and to identify putative regions or genes that could explain the CCO. METHODS: A retrospective chart review was conducted to identify patients with 22q11.2 DS seen in the ophthalmology clinic of a tertiary referral children's hospital. Thirty patients were identified, with molecular confirmation. Twenty-six did not show structural anterior segment anomalies aside from posterior embryotoxon (n = 4), whereas 4 had bilateral CCO, of which 3 had preoperative images. We reviewed medical, operative, and pathology reports; anterior segment optical coherence tomography; high-frequency ultrasound; histopathologic slides; and genetic testing. To identify putative genes responsible for CCO, chromosomal breakpoints in patients with and without CCO were compared. RESULTS: In the 3 patients with preoperative imaging and CCO, a pattern of paracentral corneal opacification with central clearing accompanied by iridocorneal or keratolenticular adhesions was observed. Anterior segment optical coherence tomography and histopathologic images showed central stromal thinning with a residual structure consistent with Descemet membrane. One patient presented at birth with unilateral corneal perforation, suggestive of likely stromal thinning. A comparison of the breakpoints across all cases failed to reveal unique regions or genes in patients with CCO. CONCLUSIONS: 22q11.2 DS can rarely be associated with CCO. We describe a consistent pattern of central clearing related to posterior stromal thinning, with or without ICA/KLA. Possible candidate genes for corneal opacification in 22q11.2 DS remain elusive.
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Opacidad de la Córnea , Perforación Corneal , Síndrome de DiGeorge , Anomalías del Ojo , Humanos , Opacidad de la Córnea/diagnóstico , Opacidad de la Córnea/genética , Opacidad de la Córnea/congénito , Síndrome de DiGeorge/diagnóstico , Síndrome de DiGeorge/genética , Anomalías del Ojo/diagnóstico por imagen , Anomalías del Ojo/genética , Estudios RetrospectivosRESUMEN
To describe the anterior segment (AS) findings in patients with microphthalmia with linear skin defects syndrome (MLS), also known as microphthalmia, dermal aplasia, and sclerocornea (MIDAS). A retrospective chart review was conducted to identify patients with a diagnosis of MLS syndrome seen at UPMC Children's Hospital of Pittsburgh. Ophthalmic examination, high-frequency ultrasound, AS optical coherence tomography, and molecular testing were reviewed. Five female patients (10 eyes) were identified. One eye was anophthalmic, one was in a status post penetrating keratoplasty, and eight eyes presented with congenital corneal opacity (CCO). Of these, one showed a normal lens and a very small faint CCO; five showed congenital aphakia and characteristic silvery appearance of the cornea with vascularization; and two showed irido-corneal adhesions in association with normal or abnormal lens and localized avascular CCO. Genetic testing was performed and revealed involvement of HCCS in four patients. In MLS patients, kerato-irido-lenticular dysgenesis can be associated with secondary CCO. It is important to distinguish these CCO from sclerocornea, in order to refine the appropriate management and counseling the parents about the prognosis.
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Opacidad de la Córnea , Microftalmía , Femenino , Humanos , Estudios Retrospectivos , Microftalmía/diagnóstico , Microftalmía/genética , Microftalmía/complicaciones , Opacidad de la Córnea/diagnóstico , Opacidad de la Córnea/genética , Síndrome , FenotipoRESUMEN
BACKGROUND: Although 8q21.11 microdeletion syndrome (8q21.11 DS) has been reported in association with congenital corneal opacities, reports of the clinicopathological features and management are scarce. METHODS: We reviewed medical records including ophthalmic evaluations, imaging, operative reports, and pathology reports of two unrelated patients referred to the Ophthalmology Clinic of UPMC Children's Hospital of Pittsburgh with a cytogenetic diagnosis of 8q21.11 DS. RESULTS: Ophthalmological evaluation of both children revealed bilateral enlarged, staphylomatous, and cloudy corneas with neovascularization. These findings were consistent with the diagnosis of congenital corneal staphyloma (CCS). In one patient, anterior segment optical coherence tomography and high-frequency ultrasound revealed materials consistent with lens remnants embedded in the cornea; this was confirmed by histopathology. In the second patient, lens was found to be adherent to the cornea during surgery. One eye underwent enucleation for corneal perforation secondary to elevated intraocular pressure. In the other eyes, treatment consisted of penetrating keratoplasty combined with vitrectomy. Ahmed tube was subsequently placed to control intraocular pressure. CONCLUSION: 8q21.11 microdeletion syndrome can be associated with bilateral CCS, likely related to a combination of anterior segment developmental anomalies and elevated intraocular pressure. Tectonic penetrating keratoplasty is necessary to prevent corneal perforation, together with a strict control of the intraocular pressure.
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Trastornos de los Cromosomas , Opacidad de la Córnea , Perforación Corneal , Anomalías del Ojo , Glaucoma , Niño , Humanos , Trastornos de los Cromosomas/patología , Córnea/patología , Opacidad de la Córnea/diagnóstico , Perforación Corneal/complicaciones , Perforación Corneal/patología , Perforación Corneal/cirugía , Anomalías del Ojo/diagnóstico , Glaucoma/patología , Queratoplastia Penetrante/métodosRESUMEN
BACKGROUND: Visual electrophysiology may be used to assess visual potential in infants with congenital corneal opacities (CCO). It is essential to recognize confounding effects from these opacities on the flash electroretinogram (ERG). METHODS: ERGs were recorded in awake children employing skin electrodes placed at the lower eyelid crease, both referred to a midfrontal electrode (Fz). A hand-held stimulator was used to present a mixed rod-cone and a dim white stimulus. Recordings were carried out before and after penetrating keratoplasty (PK), when performed. RESULTS: Five infants under the age of 12 months with visually significant CCO were evaluated. In all cases, initial ERGs employing the mixed rod-cone stimulus showed well-defined a-wave with reduced amplitude b-wave. Reduction of stimulus intensity resulted in an increase in the b-wave and normalization of the b:a ratio from 1.1 (range 0.7 to 1.3) to 2.8 (range 1.5 to 4.3). In three cases who underwent PK, the postoperative ERGs recorded with a mixed rod-cone stimulus were normal in waveform shape with a mean b:a ratio of 2.0 (range 1.7 to 3.0). CONCLUSION: Selective reduction of the scotopic bright flash ERG b-wave is typically caused by retinal dysfunction that is post-phototransduction or inner retinal. In infants with CCO, scotopic ERGs to bright flashes can show a reduced b:a ratio that improves or normalizes either after PK or stimulus intensity reduction. The study highlights that media opacity can contribute to the generation of an ERG with reduced b-wave in the absence of inner retinal dysfunction.
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Opacidad de la Córnea , Enfermedades de la Retina , Niño , Humanos , Lactante , Estimulación Luminosa/métodos , Retina , Electrorretinografía/métodos , Opacidad de la Córnea/cirugíaRESUMEN
Pathogenic variants of ADAMTSL4 are associated with autosomal recessive ectopia lentis et pupillae and isolated ectopia lentis, often presenting congenitally or in childhood. We describe a pedigree of a 4-year-old female child with bilateral ectopia lentis and her asymptomatic 35-year-old father with mild anterior segment findings. Molecular evaluation revealed compound heterozygosity for ADAMTSL4 pathogenic variants in the proband and homozygosity for an ADAMTSL4 pathogenic founder mutation in her father. The results of genetic testing revealed a pseudodominant inheritance pattern in the family. This case expands variability of ADAMTSL4-related ectopia lentis through the first description of an asymptomatic adult in the 4th decade and highlights importance of clinical and molecular evaluations of family members when investigating genetic disorders.
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Desplazamiento del Cristalino , Proteínas ADAMTS/genética , Adulto , Niño , Preescolar , Desplazamiento del Cristalino/diagnóstico , Desplazamiento del Cristalino/genética , Femenino , Humanos , Padres , Linaje , Trombospondinas/genéticaRESUMEN
PURPOSE: To describe the natural history, management, and visual outcome in children with congenital primary aphakia (CPA). METHODS: This is a multicenter retrospective consecutive case series from five academic centers in England and North America. RESULTS: A total of 27 eyes of 14 patients were included (male:female, 1.7:1). Thirteen patients had bilateral CPA, and 1 patient had unilateral CPA. Mean age at diagnosis was 18 months (median, 21; range, 0.5-144). Of 11 patients who underwent genetic testing, 9 had FOXE3 pathogenic variants. In all patients, visual acuity at presentation was not better than fixing and following light. Typical findings included silvery appearance of the cornea with vascularization (96%), glaucoma (81%), iridocorneal adhesions (74%), optic nerve coloboma (55%), abnormal vitreous (33%), retinal detachment (30%), and aniridia with hypoplasia of ciliary body (19%). Surgical interventions in select patients included penetrating keratoplasty (PKP), glaucoma drainage device implantation, and cyclophotocoagulation (CPC). CONCLUSIONS: Eyes with corneal ectasia and a silvery appearance of the cornea with vascularization should alert the physician to the possibility of CPA. Glaucoma causes globe enlargement and may increase the risk of corneal perforation, but glaucoma is often refractory to medical treatment, and the threshold for surgical treatment should be low. PKP outcomes are very poor.
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Afaquia , Presión Intraocular , Afaquia/congénito , Afaquia/genética , Afaquia/cirugía , Niño , Femenino , Estudios de Seguimiento , Humanos , Queratoplastia Penetrante , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: : Alagille syndrome (AS) is a multisystem disorder associated with a range of ocular anomalies affecting the anterior and posterior segments. While chorioretinal abnormalities have been reported in Alagille Syndrome, identification of macular dystrophy and detailed clinical and electrophysiologic descriptions are scarce. MATERIALS AND METHODS: : A retrospective review was conducted to identify patients with a diagnosis of AS and retinal disease who were evaluated in the Division of Pediatric Ophthalmology, Strabismus, and Adult Motility at UPMC Children's Hospital of Pittsburgh. Criteria of AS included biopsy-proven bile duct hypoplasia, presence of major clinical features of AS, and molecular confirmation of the JAG1 gene. RESULTS: : This cohort included three patients, two females and one male, diagnosed with JAG1-Alagille syndrome. The diagnosis was made before 2 years of life in all patients. The mean follow-up period in our center was 8 years. All patients were found to have retinal pigmentary changes, macular atrophy, choroidal thinning, optic disc anomalies, and progressive decrease in vision. Marked retinal and macular dysfunction were found in electrophysiological studies. CONCLUSIONS: : Three patients with molecularly confirmed Alagille syndrome demonstrated unusual retinal and macular findings, with two showing progressive vision loss. Due to the rarity of retinal findings in AS and the observed progression of disease in our patients, clinical genetic testing for retinal dystrophies could be completed in two cases. These investigations failed to reveal a separate molecular cause for the observed retinal dystrophy, helping to confirm the association with JAG1-related AS.
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Síndrome de Alagille , Anomalías del Ojo , Degeneración Macular , Distrofias Retinianas , Adulto , Síndrome de Alagille/diagnóstico , Síndrome de Alagille/genética , Atrofia , Niño , Femenino , Humanos , Proteína Jagged-1/genética , Degeneración Macular/diagnóstico , Degeneración Macular/genética , Masculino , RetinaRESUMEN
Linear Sebaceous Nevus Syndrome is a rare disorder that presents with nevus sebaceus in association with corneal dermoids, colobomas, choroidal osteomas, and arachnoid cysts. It is thought to represent a mosaic RASopathy. These are disorders characterized by postzygotic somatic mutation in genes involved in RAS/MAPK signaling pathway. In this report we describe two patients with linear sebaceous nevus syndrome found to have mutations in codon 146 of KRAS with evidence of mosaicism. This specific mutation has previously been reported in Oculoectodermal Syndrome and Encephalocraniocutaneous Lipomatosis, two other mosaic RASopathies with predominantly cerebrooculocutaneous manifestations. These findings suggest that, while initially classified as different syndromes, these disorders should be evaluated and managed as a spectrum of related disorders.
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Predisposición Genética a la Enfermedad , Nevo Sebáceo de Jadassohn/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Preescolar , Codón/genética , Humanos , Lactante , Sistema de Señalización de MAP Quinasas/genética , Masculino , Mosaicismo , Mutación/genética , Nevo Sebáceo de Jadassohn/diagnóstico , Nevo Sebáceo de Jadassohn/patologíaRESUMEN
We describe a novel clinical presentation of a CRX rod-cone dystrophy in a single family. Two boys ages 6 and 12 years presented with clinical and optical coherence tomography features suggestive of X-linked retinoschisis, but with optic nerve swelling without increased intracranial pressure. One patient had an electronegative electroretinogram (ERG) and the other had rod-cone dysfunction. Neither had retinoschisin (RS1) gene mutations. Biological mother and sister presented with retinal pigment epithelium (RPE) changes and abnormal cone-rod ERG responses. On further testing, next generation sequencing with array comparative genomic hybridisation showed a deletion in exon 4 of the CRX gene. Cystoid maculopathy in young male children can be difficult to distinguish from RS1-associated schisis. Phenotypic variants within a family must prompt a thorough retinal dystrophy evaluation even with electronegative ERG in the presenting child. This novel phenotype for CRX presents with optic nerve swelling and cystoid maculopathy in men, and RPE changes in women.
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Distrofias de Conos y Bastones , Enfermedades de la Retina , Retinosquisis , Niño , Electrorretinografía , Femenino , Humanos , Masculino , Mutación , Linaje , Fenotipo , Retinosquisis/diagnóstico , Retinosquisis/genética , Tomografía de Coherencia ÓpticaRESUMEN
Background: Clinical studies suggest the importance of genetic components in the etiology of keratoconus. However, the contributing genes and variants remain elusive. We present a case of bilateral keratoconus in a child with partial trisomy 13, with a trisomic region spanning loci that have been associated with keratoconus.Materials and Methods: This is a single, retrospective case report of a child with a molecular diagnosis of partial trisomy 13, who was diagnosed with bilateral keratoconus for which at the age of 11 years, she underwent successive epithelium-off corneal cross-linking (CXL) procedures in both eyes, followed by temporary central tarsorrhaphy under general anesthesia.Results: Patient's molecular diagnosis was 70 Megabase trisomic region 13q14.11q34. Pre CXL pachymetry was 426 µm and 496 µm, maximum K values were 52.28 D and 55.45 D in right and left eyes, respectively; at last follow up (12 months post-op) these were 494 µm and 509 µm for pachymetry and maximum K values 50.50 D and 52.43 D in the right and left eyes, respectively. No signs of progression were detected.Conclusion: To the best of our knowledge, this is the first case report to document bilateral keratoconus in a child with partial trisomy 13, in whom successful epithelium-off CXL was achieved with general anesthesia. We emphasize the importance of screening, early diagnosis, and therapy of this treatable but rare cause of decreased vision in partial trisomy 13 patients.
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Queratocono/genética , Síndrome de la Trisomía 13/genética , Trisomía/genética , Niño , Colágeno/metabolismo , Paquimetría Corneal , Sustancia Propia/efectos de los fármacos , Sustancia Propia/metabolismo , Topografía de la Córnea , Reactivos de Enlaces Cruzados/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Queratocono/diagnóstico por imagen , Queratocono/tratamiento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Estudios Retrospectivos , Riboflavina/uso terapéutico , Tomografía de Coherencia Óptica , Agudeza VisualRESUMEN
Congenital corneal opacities (CCO) are a group of blinding corneal disorders, where the underlying molecular mechanisms are poorly understood. Phenotyping through specialized imaging and histopathology analysis, together with assessment of key transcriptomic changes (including glycosaminoglycan metabolic enzymes) in cornea(s) with CCO from a case of Fanconi anemia is the approach taken in this study to identify causal mechanisms. Based on our findings, we propose a novel mechanism and two key players contributing to CCO.
RESUMEN
A 5-year-old girl presented with treatment-refractory dry eye and recurrent episodes of eye pain. She had been previously diagnosed with syndromic congenital sodium diarrhea (SCSD) caused by a pathogenic variant in SPINT2. Her local pediatric ophthalmologist had made the diagnosis of severe dry eye with corneal erosions, based on which, we arranged an eye exam under anesthesia (EUA) and punctal plug placement. Anterior segment optical coherence tomography (OCT) and corneal photographs were taken during the procedure. There are reports describing similar ophthalmic findings in this syndrome. However, to the best of our knowledge, this is the first case report to document OCT imaging and corneal photographs in a patient with SCSD, which we feel expands the ophthalmic phenotype of this rare genetic disorder.
Asunto(s)
Anomalías Múltiples/genética , Diarrea/congénito , Glicoproteínas de Membrana/genética , Errores Innatos del Metabolismo/genética , Sodio/metabolismo , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/diagnóstico por imagen , Anomalías Múltiples/patología , Preescolar , Córnea/metabolismo , Córnea/patología , Diarrea/diagnóstico , Diarrea/diagnóstico por imagen , Diarrea/genética , Diarrea/patología , Humanos , Errores Innatos del Metabolismo/diagnóstico , Errores Innatos del Metabolismo/diagnóstico por imagen , Errores Innatos del Metabolismo/patología , Mutación/genética , Fenotipo , Tomografía de Coherencia Óptica/métodosRESUMEN
PURPOSE: To describe our methodology for implementing synchronous telemedicine during the 2019 novel coronavirus (COVID-19) pandemic. METHODS: A retrospective review of outpatient records at a single children's hospital from March 21 to April 10, 2020, was carried out to determine the outcome of already-scheduled face-to-face outpatient appointments. The week leading up to the March 21, all appointments in the study period were categorized as follows: (1) requiring an in-person visit, (2) face-to-face visit that could be postponed, and (3) consultation required but could be virtual. Teams of administrators, schedulers, and ophthalmic technicians used defined scripts and standardized emails to communicate results of categorization to patients. Flowcharts were devised to schedule and implement telemedicine visits. Informational videos were made accessible on social media to prepare patients for the telemedicine experience. Simultaneously our children's hospital launched a pediatric on-demand e-consult service, the data analytics of which could be used to determine how many visits were eye related. RESULTS: A total of 237 virtual ophthalmology consult visits were offered during the study period: 212 were scheduled, and 206 were completed, of which 43 were with new patients and 163 with returning patients. Following the initial virtual visit, another was required on average in 4 weeks by 21 patients; in-person follow-up was required for 170 patients on average 4.6 months after the initial virtual visit. None needed review within 72 hours. The pediatric on-demand service completed 290 visits, of which 25 had eye complaints. CONCLUSIONS: With proper materials, technology, and staffing, a telemedicine strategy based on three patient categories can be rapidly implemented to provide continued patient care during pandemic conditions. In our study cohort, the scheduled clinic e-visits had a low no-show rate (3%), and 8% of the on-demand virtual access for pediatric care was eye related.