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WD40 repeat-containing proteins form a large family of proteins present in all eukaryotes. Here, we identified five pediatric probands with de novo variants in WDR37, which encodes a member of the WD40 repeat protein family. Two probands shared one variant and the others have variants in nearby amino acids outside the WD40 repeats. The probands exhibited shared phenotypes of epilepsy, colobomas, facial dysmorphology reminiscent of CHARGE syndrome, developmental delay and intellectual disability, and cerebellar hypoplasia. The WDR37 protein is highly conserved in vertebrate and invertebrate model organisms and is currently not associated with a human disease. We generated a null allele of the single Drosophila ortholog to gain functional insights and replaced the coding region of the fly gene CG12333/wdr37 with GAL4. These flies are homozygous viable but display severe bang sensitivity, a phenotype associated with seizures in flies. Additionally, the mutant flies fall when climbing the walls of the vials, suggesting a defect in grip strength, and repeat the cycle of climbing and falling. Similar to wall clinging defect, mutant males often lose grip of the female abdomen during copulation. These phenotypes are rescued by using the GAL4 in the CG12333/wdr37 locus to drive the UAS-human reference WDR37 cDNA. The two variants found in three human subjects failed to rescue these phenotypes, suggesting that these alleles severely affect the function of this protein. Taken together, our data suggest that variants in WDR37 underlie a novel syndromic neurological disorder.
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Transtornos Dismórficos Corporais/patologia , Cerebelo/anormalidades , Coloboma/patologia , Deficiências do Desenvolvimento/patologia , Epilepsia/patologia , Deficiência Intelectual/patologia , Mutação , Malformações do Sistema Nervoso/patologia , Repetições WD40/genética , Adulto , Sequência de Aminoácidos , Animais , Transtornos Dismórficos Corporais/genética , Cerebelo/patologia , Criança , Coloboma/genética , Deficiências do Desenvolvimento/genética , Drosophila melanogaster/genética , Drosophila melanogaster/crescimento & desenvolvimento , Epilepsia/genética , Feminino , Humanos , Lactente , Recém-Nascido , Deficiência Intelectual/genética , Masculino , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Malformações do Sistema Nervoso/genética , Fenótipo , Homologia de Sequência , Adulto JovemRESUMO
A 50-year-old female presented with a slowly enlarging painless mass of the right medial canthus. The past surgical history is significant for external dacryocystorhinostomy for acquired nasolacrimal duct obstruction 10 years prior and subsequent endoscopic and external revisions. Imaging revealed a large fronto-ethmoidal sinus mucocele extending into the right medial orbit. On surgical exploration, the right middle turbinate was found to have lateralized, obstructing sinus outflow. The mucocele was evacuated and ethmoidectomy and middle turbinectomy were performed. The patient did well postoperatively without recurrence at 6 months of follow-up. Sinus mucocele formation is a rare, late complication of lacrimal surgery.
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Dacriocistorinostomia/efeitos adversos , Seio Etmoidal , Mucocele/etiologia , Doenças dos Seios Paranasais/etiologia , Complicações Pós-Operatórias , Feminino , Seguimentos , Humanos , Doenças do Aparelho Lacrimal/cirurgia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Mucocele/diagnóstico , Doenças dos Seios Paranasais/diagnóstico , Fatores de TempoRESUMO
PURPOSE: To investigate whether the 2-year change in lens opacity severity on the Age-Related Eye Disease Study (AREDS) lens grading scale predicts progression to cataract surgery or loss of visual acuity by 5 years. DESIGN: Prospective cohort study within a randomized clinical trial of oral supplements. PARTICIPANTS: The AREDS participants whose eyes were phakic at baseline and free of late age-related macular degeneration throughout the study. METHODS: Baseline and annual lens photographs of AREDS participants (n = 3466/4757; 73%) were graded for severity of cataracts using the AREDS system for classifying cataracts from photographs. Clinical examinations conducted semiannually collected data on cataract surgery and visual acuity. Association of the change in lens opacities at 2 years with these outcomes at 5 years was analyzed with adjusted Cox proportional hazard models. MAIN OUTCOME MEASUREMENTS: Progression of lens opacities on stereoscopic lens photographs at 2 years, cataract surgery, and visual acuity loss of 2 lines or more at 5 years. RESULTS: The adjusted hazard ratios (HRs) for association of progression to cataract surgery at 5 years were: nuclear cataract increase of 1.0 unit or more compared with less than 1.0-unit change at 2 years, 2.77 (95% confidence interval [CI], 2.07-3.70; P < 0.001); cortical cataract increase of 5% or more in lens opacity in the central 5 mm of the lens compared with less than 5% increase at 2 years, 1.91 (95% CI, 1.27-2.87; P = 0.002); and posterior subcapsular cataract increase of 5% or more versus less than 5% in the central 5 mm of the lens, 8.25 (95% CI, 5.55-12.29; P < 0.001). Similarly, HRs of vision loss of 2 lines or more at 5 years for this degree of lens changes at 2 years were the following: nuclear, 1.83 (95% CI, 1.49-2.25; P < 0.001); cortical, 1.13 (95% CI, 0.78-1.65; P = 0.519); and posterior subcapsular cataract, 3.05 (95% CI, 1.79-5.19; P < 0.001). CONCLUSIONS: Two-year changes in severity of lens opacities on the AREDS lens grading scale are predictive of long-term clinically relevant outcomes, making them potential surrogate end points in follow-up studies.
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Cegueira/diagnóstico , Extração de Catarata , Catarata/classificação , Catarata/diagnóstico , Degeneração Macular/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Progressão da Doença , Feminino , Seguimentos , Humanos , Degeneração Macular/classificação , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Índice de Gravidade de Doença , Acuidade Visual/fisiologiaRESUMO
Purpose: The purpose of this study is to describe a case of unilateral keratoconus associated with ipsilateral craniofacial fibrous dysplasia and its subsequent management with corneal collagen cross-linking. Observations: This is an interventional case report of a 16-year-old male with a history of polyostotic fibrous dysplasia of the left frontal bone and orbital roof status post partial resection six years prior who presented to the pediatric ophthalmology clinic with progressively blurry vision in the left eye. Refraction in this eye revealed an increase in cylinder by > 3D from his last refraction two years prior. Pentacam corneal tomography confirmed the diagnosis of keratoconus in the left eye. The patient underwent corneal collagen cross-linking in the affected eye. Postoperatively, he experienced marked improvement in corrected visual acuity with scleral contact lenses and maintained stable astigmatism and keratometry values on Pentacam corneal tomography at his most recent visit 12 months postoperatively. Conclusions: While it is otherwise felt to be a bilateral disease, unilateral keratoconus may present in the context of ipsilateral orbital pathology. Corneal collagen cross-linking may be used to successfully prevent keratoconus progression in the setting of stable orbital pathology.
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PURPOSE: To compare outcomes and complications of three surgical techniques for the treatment of congenital dacryocystoceles: nasolacrimal probing and irrigation (P+I), P+I plus nasal endoscopy (NE) with intranasal cyst marsupialization, and primary NE with intranasal cyst marsupialization. METHODS: The medical records of children ≤2 years of age at a single academic center with a diagnosis of dacryocystocele from 2012 to 2022 were retrospectively identified and reviewed. The primary outcome was resolution of the dacryocystocele (ie, elimination of the medial canthal mass and resolution of tearing or discharge) after a single procedure ("primary success"). Surgical techniques were compared using exact logistic regression. RESULTS: Of 54 patients, 21 (39%) underwent P+I, 23 (43%) underwent P+I plus nasal endoscopy, and 10 (18%) underwent primary NE. Primary success was 76% for P+I and 100% for the other two cohorts. Most patients (89%) who underwent P+I received general anesthesia compared with none who underwent primary nasal endoscopy. Most complications were related to the use of general anesthesia, with a complication rate of 10% for P+I, 48% for P+I plus NE, and 0% for primary NE. Most P+I procedures required hospital admission compared to half of primary NE procedures. CONCLUSIONS: In our study cohort, primary NE provided good outcomes and was associated with a lower complication rate than P+I with or without NE.
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Cistos , Dacriocistorinostomia , Obstrução dos Ductos Lacrimais , Ducto Nasolacrimal , Criança , Humanos , Lactente , Dacriocistorinostomia/métodos , Estudos Retrospectivos , Obstrução dos Ductos Lacrimais/diagnóstico , Obstrução dos Ductos Lacrimais/terapia , Obstrução dos Ductos Lacrimais/congênito , Ducto Nasolacrimal/cirurgia , Endoscopia/métodos , Cistos/diagnóstico , Resultado do TratamentoRESUMO
PURPOSE: To investigate the results of patients undergoing surgical treatment for strabismic diplopia in thyroid eye disease (TED) following teprotumumab. DESIGN: Multicenter, retrospective, case series. METHODS: We report 28 patients who underwent extraocular muscle surgery for strabismic diplopia after treatment with teprotumumab at 7 different academic centers. Elapsed time from last teprotumumab dose to the date of surgery, previous orbital decompression, primary preoperative horizontal and vertical deviation, surgical procedure, and 2-month postoperative results were collected from the patient records. RESULTS: Sixteen (57%) patients were diplopia-free after 1 surgery. Three (11%) chose prism spectacles to correct residual diplopia, 2 (7%) used compensatory head posture to resolve diplopia, and 1 (4%) had intermittent diplopia and was functionally improved (choosing no prisms or further surgery). These were considered treatment successes. Three (11%) patients required reoperation, and all were diplopia-free after their second procedure. CONCLUSIONS: Most patients requiring surgery for strabismic diplopia following teprotumumab achieve good outcomes with success rates comparable to series published before the availability of teprotumumab.
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Anticorpos Monoclonais Humanizados , Diplopia , Oftalmopatia de Graves , Músculos Oculomotores , Estrabismo , Humanos , Estudos Retrospectivos , Masculino , Feminino , Músculos Oculomotores/cirurgia , Músculos Oculomotores/fisiopatologia , Pessoa de Meia-Idade , Oftalmopatia de Graves/cirurgia , Oftalmopatia de Graves/tratamento farmacológico , Diplopia/fisiopatologia , Estrabismo/cirurgia , Estrabismo/fisiopatologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Idoso , Adulto , Resultado do Tratamento , Procedimentos Cirúrgicos Oftalmológicos , Descompressão Cirúrgica , Visão Binocular/fisiologiaRESUMO
The authors report a case of lacrimo-auriculo-dento-digital syndrome in a 16-month-old boy with punctal agenesis, upper canalicular dysgenesis and polydactyly, presenting as bilateral congenital nasolacrimal duct obstruction and unilateral acute dacryocystitis. Genetic sequencing revealed a novel mutation in fibroblast growth factor 10. [J Pediatr Ophthalmol Strabismus. 2023;60(4):e38-e40.].
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Perda Auditiva , Obstrução dos Ductos Lacrimais , Ducto Nasolacrimal , Masculino , Humanos , Lactente , Obstrução dos Ductos Lacrimais/diagnóstico , Obstrução dos Ductos Lacrimais/terapia , Obstrução dos Ductos Lacrimais/complicações , Fator 10 de Crescimento de FibroblastosRESUMO
Facial feminization surgery (FFS), or gender-affirming facial surgery, is a common procedure for patients with gender dysphoria. One goal of FFS involves extensive contouring of the frontal and nasal bones to reduce supraorbital bossing. Ophthalmic complications after FFS have been rarely reported. We report 2 cases of superior oblique palsy after FFS producing persistent vertical and torsional diplopia. One case was successfully treated with prism spectacles; the other required surgical management. Both cases likely involved surgical trauma to or disinsertion of the trochlea during orbital bony reshaping.
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Feminização , Doenças do Nervo Troclear , Masculino , Humanos , Feminização/cirurgia , Olho , Doenças do Nervo Troclear/cirurgia , Diplopia/etiologia , ParalisiaRESUMO
Keratoconus is a disorder characterized by progressive corneal thinning and steepening that may result in significant visual impairment secondary to high astigmatism, corneal scarring, or even corneal perforation. Early detection and screening of keratoconus are essential for effective management and treatment. Several screening methods, such as corneal topography and tomography, corneal biomechanics, and genetic testing, are being developed to detect keratoconus at an early stage. Once detected, prevention of progression is the mainstay of keratoconus management. Corneal collagen cross-linking is a minimally invasive treatment option that can slow or halt the progression of keratoconus. Additionally, recent studies have investigated the potential use of copper sulfate eye drops (IVMED-80) and extracellular vesicles to prevent the progression of keratoconus as non-invasive treatment options. For visual rehabilitation, currently available treatments include scleral lenses, intracorneal ring segments, corneal allogenic intrastromal ring segments, and deep anterior lamellar keratoplasty. The safety and efficacy of these emerging treatment options for keratoconus are currently being investigated.
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PURPOSE: The purpose of this study was to investigate the social determinants of health for keratoconus. METHODS: In this retrospective cohort study of patients with keratoconus, the electronic health record was reviewed for keratometry, treatments received, clinical comorbidities, and social characteristics. Outcomes included severe keratoconus at presentation (steep keratometry ≥52 diopters), disease progression (≥0.75 diopters increase from the first to the most recent clinical visit), and corneal transplantation. Logistic regression was used to evaluate factors associated with severity at presentation and corneal transplantation. Cox proportional hazards modeling was used to evaluate progression. RESULTS: A total of 1038 patients with keratoconus were identified, 725 (70%) of whom had baseline imaging. Compared with commercially insured patients, Medicaid recipients were more likely to have severe keratoconus, independent of social and clinical confounders [odds ratio (OR) 1.94, 95% confidence interval (CI), 1.12-3.35, P = 0.017]. Male sex was independently associated with progression (hazard ratio = 1.38, 95% CI, 1.03-1.84, P = 0.030). Medicare and Medicaid recipients were more likely to require transplantation compared with commercially insured patients (OR 2.71, 95% CI, 1.65-4.46, P < 0.001 and OR 1.74, 95% CI, 1.08-2.80, P = 0.022, respectively). Other social determinants of health, including non-White race/ethnicity, limited English proficiency, and unemployment, were associated with the outcomes only in univariate analysis. Obstructive sleep apnea, atopy, body mass index, and tobacco use were not associated with any outcome. CONCLUSIONS: Socioeconomic factors were more consistent predictors of keratoconus severity and corneal transplantation compared with clinical factors that have received relatively greater attention in the keratoconus literature.
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Ceratocone , Idoso , Estados Unidos/epidemiologia , Humanos , Masculino , Ceratocone/diagnóstico , Ceratocone/epidemiologia , Estudos Retrospectivos , Medicare , Córnea , Progressão da Doença , Fatores Socioeconômicos , Topografia da CórneaAssuntos
Disceratose Congênita/complicações , Vitreorretinopatia Proliferativa/etiologia , Pré-Escolar , Disceratose Congênita/genética , Exsudatos e Transudatos , Angiofluoresceinografia , Humanos , Fotocoagulação a Laser , Masculino , Mutação , Proteínas de Ligação a Telômeros/genética , Vitreorretinopatia Proliferativa/diagnóstico , Vitreorretinopatia Proliferativa/cirurgiaRESUMO
Purpose: To describe a case of incomitant divergence insufficiency esotropia in the setting of Machado-Joseph disease (spinocerebellar ataxia type 3) that recurred completely within one week after augmented bilateral medial rectus recession. Observations: A 53-year-old female with a history of Machado-Joseph disease presented with horizontal diplopia primarily at distance consistent with divergence insufficiency esotropia. Augmented bilateral medial rectus recessions were performed which initially produced orthotropia, but recurrence of the esodeviation to the full preoperative amount occurred by post-operative week one. The patient subsequently underwent bilateral lateral rectus resections with excellent result. Conclusions and importance: Divergence insufficiency is common in the spinocerebellar ataxia variants and is thought to be secondary to atrophy of brainstem structures involved in the control of ocular vergence. Strabismus surgery in these patients may be complicated by limited response or even rapid regression despite augmented surgery as suggested for divergence insufficiency in the setting of neurologic disease. Patients should be counseled on these risks as well as the potential for multiple procedures in order to achieve surgical success.
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Purpose: To assess the impact of parental socioeconomic status and keratoconus literacy on pediatric eye rubbing and keratoconus severity. Methods: In this mixed-methods study, pediatric keratoconus patients (age ≤ 18 years) were retrospectively identified. Sociodemographic and clinical characteristics were extracted from the electronic medical record (EMR). Telephone surveys were subsequently conducted to assess parental keratoconus literacy, receipt of counseling on keratoconus prevention, eye rubbing, and household socioeconomic factors not available in the EMR. Parents reporting poor keratoconus literacy were probed via semi-structured interview to explore barriers to their understanding. Results: Forty-eight patients met inclusion criteria, 22 (46%) of whom were reached by telephone. Most patients were insured by Medicaid (73%) and current eye rubbers (82%). Few parents reported good or excellent keratoconus literacy now (32%) or at the time of diagnosis (18%). Parents with a high-school education, limited English proficiency, lower income level, and Medicaid insurance tended to have lower keratoconus literacy, though this was not statistically significant. Parental keratoconus literacy was not correlated with disease severity. High-school education, limited English proficiency, lower income level, and Medicaid insurance were correlated with steeper keratometry readings, which was statistically significant for high-school education. In-depth interviews revealed parents felt unconfident with eye health in general and perceived a personal responsibility for learning more. Conclusion: This is the first study exploring keratoconus literacy from a socioeconomic perspective, demonstrating lower literacy among socioeconomically marginalized parents and a tendency toward more severe disease in their children.
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Purpose: The objective of this study was to identify the prevalence of CMV ocular disease in children and to identify associated risk factors for ocular involvement. Design: Retrospective multicenter, cross-sectional study. Methods: Setting: Hospitalized patients screened for CMV viremia by PCR between 2005 and 2018 at four pediatric referral centers. Participants: Seven-hundred and ninety-three children showed CMV viremia (>135 copies/mL by polymerase chain reaction; PCR). Main Outcomes and Measures: (1) Occurrence of ophthalmologic examination. (2) Presence of CMV ocular disease, defined as retinitis, vasculitis, hemorrhage, optic nerve atrophy, or anterior uveitis in the setting of CMV viremia without other identifiable causes. Results: A total of 296/793 (37%) underwent ophthalmologic examination following CMV viremia. A total of23/296 patients (8%) had ocular symptoms prompting evaluation while the rest had eye exams for baseline screening unrelated to CMV viremia. Of these, 13 cases (4% of those with an eye exam) with ocular disease were identified (three congenital CMV, five severe combined immunodeficiency disorder (SCID) status post-stem cell transplantation, three hematologic malignancy status post-stem cell transplantation for two of them, one Evans syndrome status post-stem cell transplantation, and one medulloblastoma status post-bone marrow transplantation). No patients with solid organ transplantation developed CMV ocular disease in our cohort. Conclusion: CMV ocular disease was a rare occurrence in this cohort without an identifiable pattern across sub-groups. Excluding the three congenital CMV cases, nine out of ten patients with CMV ocular disease were status post-stem cell transplantation. We provide integrated screening guidelines based on the best available evidence for this rare condition.
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Purpose: To describe trends in the use of corneal topography and tomography for the management of keratoconus patients at a single academic institution and to identify how these trends may be associated with different procedural interventions. Patients and Methods: In this retrospective cohort study, keratoconus patients treated from 2012 to 2019 were identified. The electronic health record was reviewed for the presence of corneal topography or tomography imaging completed within seven days of the first visit and the highest level of intervention at the first and most recent visit. Patients were grouped as pediatric (<18 years) or adult (≥18 years). Chi-square tests and linear regressions were used to evaluate trends and to determine which factors were predictive for receiving corneal collagen cross-linking (CXL) versus other surgical interventions (intrastromal corneal ring segments, lamellar keratoplasty, or penetrating keratoplasty) by the most recent visit. Results: A total of 873 keratoconus patients met inclusion criteria. The use of corneal topography at the first visit remained relatively consistent from 2012 to 2019, while corneal tomography usage at the first visit increased from 3.9% in 2015, when corneal tomography was introduced, to 52.8% in 2019. Each year was associated with an 11.2% ± 1.9% increase in the use of corneal tomography at the first visit in pediatric patients and 6.7% ± 0.5% in adult patients. Use of corneal tomography at the first visit was a significant predictor for receiving CXL procedures (P < 0.001) and a negative predictor for requiring other surgical interventions (P = 0.032) when controlling for the year of the first visit. Conclusion: Obtaining corneal tomography at the first visit has become the standard of care in keratoconus, especially for pediatric patients. Moreover, the increase in corneal tomography imaging has coincided with an increase in CXL procedures and decrease in other surgical interventions.
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Community transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) in the United States on February 26, 2020, and the rapid spread that followed forced patients, providers, payors, and policy makers to adapt to an unprecedented, nearly instant, and enormous demand for virtual care. Although few US ophthalmology practices incorporated telemedicine prior to COVID-19, its use has now become the norm. Regarding the use of synchronous patient-to-provider virtual visits (SPPVV) in pediatric ophthalmology, we have pooled our collective experience at three academic practices across the country to describe initial workflows, technology solutions, use cases, and barriers to care.
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COVID-19/epidemiologia , Oftalmopatias/epidemiologia , Oftalmologia/métodos , Pandemias , SARS-CoV-2 , Telemedicina/organização & administração , Criança , Comorbidade , Oftalmopatias/diagnóstico , Humanos , Estados Unidos/epidemiologiaRESUMO
PURPOSE: To report the clinical characteristics and outcomes of pediatric patients with keratoconus (KCN) who underwent corneal collagen cross-linking (CXL) under general anesthesia for developmental delay or inability to cooperate with topical anesthesia. METHODS: In this retrospective case series, we reviewed the medical charts of pediatric patients with KCN who had CXL under general anesthesia from January 2018 to April 2019. Baseline disease characteristics of patients with and without developmental delay were compared using the Pearson χ test and the t test. Main outcomes were anesthesia or surgical complications and postoperative best corrected visual acuity (BCVA), keratometry (K) values, and caregiver report of eye-rubbing behavior. RESULTS: Fourteen eyes of 9 patients were reviewed. All were habitual eye rubbers at baseline. Six (66.7%) were developmentally delayed. Compared with patients without developmental delay, developmentally delayed patients were diagnosed and treated at older ages (16.0 vs. 13.9 years), experienced longer delays from diagnosis to surgery (20.7 vs. 8.8 weeks), and had lower BCVA (20/70 vs. 20/40), higher steep K values (54.0 vs. 50.9), and a higher incidence of corneal scarring (75.0% vs. 33.3%) and monocular vision loss (50.0% vs. 0.0%) at baseline, although these differences were not statistically significant. No anesthesia or surgical complications occurred. BCVA and K values were stable at postoperative month 6, with no clinically or statistically significant change observed for either measure. Eight patients decreased or stopped eye rubbing. CONCLUSIONS: We demonstrate the efficacy and safety of CXL under general anesthesia in halting the progression of KCN for pediatric patients with developmental delay or an inability to cooperate with the procedure until topical anesthesia.
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Anestesia Geral/métodos , Colágeno/uso terapêutico , Reagentes de Ligações Cruzadas/uso terapêutico , Deficiências do Desenvolvimento/complicações , Ceratocone/tratamento farmacológico , Fotoquimioterapia/métodos , Riboflavina/uso terapêutico , Adolescente , Topografia da Córnea/métodos , Feminino , Seguimentos , Humanos , Ceratocone/complicações , Ceratocone/diagnóstico , Masculino , Fármacos Fotossensibilizantes/uso terapêutico , Refração Ocular , Estudos Retrospectivos , Resultado do Tratamento , Acuidade VisualRESUMO
PURPOSE: Advances in surgical techniques allow implantation of intraocular lenses (IOL) with cataract extraction, even in young children. However, there are several challenges unique to the pediatric population that result in greater degrees of postoperative refractive error compared to adults. METHODS: Literature review of the techniques and outcomes of pediatric cataract surgery with IOL implantation. RESULTS: Pediatric cataract surgery is associated with several sources of postoperative refractive error. These include planned refractive error based on age or fellow eye status, loss of accommodation, and unexpected refractive errors due to inaccuracies in biometry technique, use of IOL power formulas based on adult normative values, and late refractive changes due to unpredictable eye growth. CONCLUSIONS: Several factors can preclude the achievement of optimal refractive status following pediatric cataract extraction with IOL implantation. There is a need for new technology to reduce postoperative refractive surprises and address refractive adjustment in a growing eye.