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Inteligencia Artificial , Retina , Humanos , Tamizaje Masivo , Retina/diagnóstico por imagenRESUMEN
OBJECTIVES: To evaluate the long-term outcomes of intrascleral haptic fixation of posterior chamber intraocular lens (PCIOL) with fibrin glue in children. METHODS: This is a retrospective case study conducted in a tertiary eye institute in North India. A total of 118 eyes of 82 children who underwent glued intrascleral haptic fixation of PCIOLs were retrospectively analyzed. Detailed analysis of the indication for surgery and ocular and systemic associations was performed. The outcome measures included intraoperative complications, final visual and refractive outcomes, and postoperative complications. RESULTS: The mean age of the patients was 10.16±3.94 years. Fifty-one patients (62.2%) were male and 31 (37.8%) were female. The mean follow-up period was 31.28±13.22 months. The mean preoperative corrected distance visual acuity was 1.18±0.63 Logarithm of Mean angle of resolution (logMAR) which improved to 0.60±0.58 logMAR postoperatively at 6 weeks (P<0.001). The mean preoperative and 6 weeks postoperative endothelial cell density were 3,176.08±318.6 and 2,936±289.9 cells/mm2, respectively (P=0.23). In the immediate postoperative period, corneal edema (19 eyes; 16.1%), decentered IOL/tilt (3 eyes; 2.54%), vitreous hemorrhage (3 eyes; 2.54%), optic capture (4 eyes; 3.38%), and hypotony (2 eyes; 1.69%) were seen. In the late postoperative period (>6 weeks), retinal detachment was observed in two eyes that had associated Marfan syndrome. Cystoid macular edema was seen in four eyes (3.38%), and glaucoma was seen in five eyes (4.23%). CONCLUSIONS: Fibrin glue-assisted intrascleral haptic fixation of a PCIOL is a safe and effective method to manage aphakia with inadequate capsular support in children.
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Adhesivo de Tejido de Fibrina , Lentes Intraoculares , Adolescente , Niño , Femenino , Adhesivo de Tejido de Fibrina/uso terapéutico , Tecnología Háptica , Humanos , India , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND: Precision genome engineering, with targeted therapy towards patient-specific mutations is predicted to be the future of personalized medicine. Ophthalmology is in the frontiers of development of targeted therapy since the eye is an accessible organ and has the ease of both delivery as well as monitoring effects of therapy. MATERIALS AND METHODS: We reviewed literature using keywords CRISPR, precision medicine, genomic editing, retinal dystrophies, retinitis pigmentosa, Usher syndrome, Stargardt's Disease. Further, we collated data on current clinical trials. RESULTS: There is growing evidence on the role of genomic editing in retinal dystrophies, the various methods used, and stage of development of different therapies have been summarized in this paper. CONCLUSIONS: The CRISPR-Cas9 system has revolutionized genome editing, and opened avenues in drug discovery. It is important to understand the role of this system along with its applicability in the field of ophthalmology. In this review article, we briefly describe its methodology, the strategies of employing it for making genetic perturbations, and explore its applications in inherited retinal dystrophies.
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Proteína 9 Asociada a CRISPR/genética , Edición Génica/métodos , Genoma Humano/genética , Distrofias Retinianas/genética , Terapia Genética , Medicina Genómica , HumanosRESUMEN
While asthma has a strong genetic component, our current ability to systematically understand and predict asthma risk remains low, despite over a hundred genetic associations. The reasons for this unfilled gap range from technical limitations of current approaches to fundamental deficiencies in the way we understand asthma. These are discussed in the context of genomic advances.
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Antiasmáticos/farmacología , Asma/genética , Epigénesis Genética , Estudio de Asociación del Genoma Completo , Microbiota/fisiología , Asma/tratamiento farmacológico , Asma/microbiología , Biomarcadores , Interacción Gen-Ambiente , Ligamiento Genético , Humanos , Receptores de Lipopolisacáridos/genética , Pulmón/microbiología , Linaje , Pruebas de Farmacogenómica , Medicina de Precisión , Transcriptoma , Estudios en Gemelos como AsuntoRESUMEN
Ophthalmic genetics is a much needed and growing area in India. Ethnic diversity, with a high degree of consanguinity, has led to a high prevalence of genetic disorders in the country. As the second most populous country in the world, this naturally results in a significant number of affected people overall. Practice involves coherent association between ophthalmologists, genetic counselor and pediatricians. Eye genetics in India in recent times has witnessed advanced research using cutting edge diagnostics, next generation sequencing (NGS) approaches, stem cell therapies, gene therapy and genomic editing. This article will highlight the studies reporting genetic variations in the country, challenges in practice, and the latest advances in ophthalmic genetic research in India.
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Enfermedades Hereditarias del Ojo/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Oftalmología/tendencias , Medicina de Precisión , Enfermedades Hereditarias del Ojo/diagnóstico , Enfermedades Hereditarias del Ojo/patología , Enfermedades Hereditarias del Ojo/terapia , Investigación Genética , Genoma Humano/genética , Genómica/tendencias , Humanos , India/epidemiologíaRESUMEN
The original version of this Article contained errors in Fig. 8. In panel a, the labels 'VEGF', 'Notch', 'p21', and 'P-ERK' were inadvertently omitted. This has been corrected in the PDF and HTML versions of the Article.
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Appropriate therapeutic modulation of endothelial proliferation and sprouting is essential for the effective inhibition of angiogenesis in cancer or its induction in cardiovascular disease. The current view is that an increase in growth factor concentration, and the resulting mitogenic activity, increases both endothelial proliferation and sprouting. Here, we modulate mitogenic stimuli in different vascular contexts by interfering with the function of the VEGF and Notch signalling pathways at high spatiotemporal resolution in vivo. Contrary to the prevailing view, our results indicate that high mitogenic stimulation induced by VEGF, or Notch inhibition, arrests the proliferation of angiogenic vessels. This is due to the existence of a bell-shaped dose-response to VEGF and MAPK activity that is counteracted by Notch and p21, determining whether endothelial cells sprout, proliferate, or become quiescent. The identified mechanism should be considered to achieve optimal therapeutic modulation of angiogenesis.
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Endotelio Vascular/efectos de los fármacos , Mitógenos/farmacología , Neovascularización Patológica/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Animales , Proliferación Celular/efectos de los fármacos , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Endotelio Vascular/patología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Ratones , Ratones Noqueados , Neovascularización Patológica/patología , Receptores Notch/antagonistas & inhibidores , Receptores Notch/metabolismo , Retina , Vasos Retinianos , Transducción de Señal/genética , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVES: Diffuse axonal injury is one of the major causes of unconsciousness, profound neurologic deficits and persistent vegetative state after head trauma. In recent years, MR imaging has been gaining popularity as an adjunctive imaging method in patients with DAI. Our study aims to assess the relative diagnostic and prognostic capability of various MRI sequences. PATIENTS AND METHODS: Retrospective observational study done in 1 year duration on 30 DAI patients. Clinical assessment done with GCS at admission and GOS at 6 month. MRI Brain FLAIR, DWI, T2*GRE AND SWI sequences taken. DAI grade were evaluated for different MRI sequences. Prognosis was correlated to total number of lesion/locations and DAI grade of patients. Statistical analysis was done using SPSS Statistical software (ver.20.0.0) and XL-Stat and ANOVA one way test, post hoc test (Turkey test) and Chi square test. RESULT: We studied 30 male patients, mean age 32.57±8.72 ranges. The commonest mode of injury is RTA-80%, fall-16% followed by assault-3.33%. Out of 30 patients, 17 patients (56.67%) had GCS <=8, 13 patients (43.33%) had GCS between 9 and 12 and no patient had a GCS score between 13 and 15. The mean GCS score was 8.47±1.50. At a 6 month follow up, out of a total of 30 patients, 2 patients (6.66%) expired (GOS-1), 3 patients (10%) remained in persistent vegetative state (GOS-2), 11 patients (36.67%) and 10 patients (33.33%) were found to be severely (GOS-3) and moderately (GOS-4) disabled respectively and 4 patients (13.33%) showed good recovery (GOS-5). Mean GOS is 3.37+/-1.06. Newer imaging -SWI able to detects lesion better (diagnosis of DAI) as compared to other older sequences like FLAIR,DWI,T2*GRE. But no statistically significant found between total number of lesion/locations to the outcome and also newer imaging do not change the grade of DAI patients. CONCLUSION: Although advanced imaging in head injury, SWI helps in diagnosing the diffuse axonal injury more efficiently than other imaging sequences, but it is the grade of patients at admission that predicts the outcome best.
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Improved methods for manipulating and analyzing gene function have provided a better understanding of how genes work during organ development and disease. Inducible functional genetic mosaics can be extraordinarily useful in the study of biological systems; however, this experimental approach is still rarely used in vertebrates. This is mainly due to technical difficulties in the assembly of large DNA constructs carrying multiple genes and regulatory elements and their targeting to the genome. In addition, mosaic phenotypic analysis, unlike classical single gene-function analysis, requires clear labeling and detection of multiple cell clones in the same tissue. Here, we describe several methods for the rapid generation of transgenic or gene-targeted mice and embryonic stem (ES) cell lines containing all the necessary elements for inducible, fluorescent, and functional genetic mosaic (ifgMosaic) analysis. This technology enables the interrogation of multiple and combinatorial gene function with high temporal and cellular resolution.
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Marcación de Gen/métodos , Animales , Línea Celular , Células Madre Embrionarias , Ratones , Ratones TransgénicosRESUMEN
PURPOSE: To compare the clinical outcomes between sutured transscleral-fixated and intrascleral haptic-fixated posterior chamber intraocular lens (IOL). SETTING: Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi. DESIGN: A comparative case series. METHODS: Forty eyes of 40 patients were included; 20 in each group. Patients in group 1 underwent sutured transscleral-fixated IOL and those in group 2 underwent intrascleral haptic-fixated IOL augmented by fibrin glue. Parameters evaluated were uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CMT), IOL tilt on ultrasound biomicroscopy (UBM), and pseudophakodonesis on slitlamp and UBM. RESULTS: The most common cause of aphakia was complicated cataract surgery (50%). The mean preoperative UCVA in logarithm of minimum angle of resolution (logMAR) was 1.59±0.24 and 1.63±0.26 in group 1 and 2, respectively (P=0.45). There was significant improvement in UCVA in both groups (P=0.001) at 6 months (group 1: 0.33±0.17; group 2: 0.22±0.10); the improvement being greater in group 2 (P<0.05). Mean percentage endothelial cell loss and IOP change were comparable. Mean CMT (µm) was 250.95±23.98 and 225.85±21.13 in group 1 and 2, respectively (P=0.009). Pseudophakodonesis was more in group 1 as assessed on slitlamp (P=0.037) and as assessed on UBM (P=0.046). Macular edema was the most common complication seen more in group 1. CONCLUSIONS: Intrascleral haptic-fixated IOL provides more stable fixation, better visual outcome, and lesser complication in comparison with sutured transscleral-fixated IOL.
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Afaquia/cirugía , Implantación de Lentes Intraoculares/métodos , Lentes Intraoculares , Esclerótica/cirugía , Técnicas de Sutura , Adulto , Anciano , Afaquia/fisiopatología , Femenino , Humanos , Presión Intraocular/fisiología , Mácula Lútea/patología , Masculino , Persona de Mediana Edad , Agudeza Visual/fisiología , Adulto JovenRESUMEN
OBJECTIVE: The objective of this study was to review the treatment outcomes of patients with secondary glaucoma in cases of autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), a hereditary autoimmune uveitis due to mutations in CAPN5. PATIENTS AND METHODS: A retrospective, observational case series was assembled from ADNIV patients with secondary glaucoma. The main outcome measures were intraocular pressure (IOP), visual acuity, use of antiglaucoma medications, ocular surgeries, and adverse outcomes. Perimetry and optic disk optical coherence tomography (OCT) were also analyzed. RESULTS: Nine eyes of five ADNIV patients with secondary glaucoma were reviewed. Each received a fluocinolone acetonide (FA) implant for the management of posterior uveitis. Following implantation, no eyes developed neovascular glaucoma. Five eyes (in patients 1, 2, and 5) required Ahmed glaucoma valve surgery for the management of steroid-responsive glaucoma. Patient 2 also developed angle closure with iris bombe and underwent laser peripheral iridotomy. Patient 4 had both hypotony and elevated IOP that required periodic antiglaucoma medication in the FA-implanted eye. Patient 3 did not develop steroid-response glaucoma in either eye. Optic disk examinations were obscured by fibrosis and better assessed with OCT. CONCLUSION: ADNIV patients show combined mechanism secondary glaucoma best assessed by OCT of the optic disk. The FA implants have reduced uveitic and neovascular glaucoma. Nevertheless, IOP management remains complex due to steroid-response glaucoma, angle closure glaucoma, and hypotony.
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PURPOSE: The aim of this study was to evaluate the surgical outcomes of a modified approach in the management of thick submacular hemorrhage in patients with wet age-related macular degeneration. DESIGN: This was a retrospective study. METHODS: A retrospective chart review was performed on 10 eyes of 10 patients with submacular hemorrhage secondary to wet age-related macular degeneration treated with 23-gauge pars plana vitrectomy, followed by submacular injection of recombinant tissue plasminogen activator (12.5 µg/0.1 mL), bevacizumab (2.5 mg/0.1 mL), and air (0.3 mL). Gas tamponade was given with 20% SF6 and postoperative propped-up positioning. Patients were evaluated for displacement of hemorrhage, preoperative and postoperative best-corrected visual acuity, occurrence of intraoperative and postoperative complications, and recurrence of hemorrhage. All patients were followed up for 6 months. RESULTS: Displacement of the submacular bleed was achieved in all cases. Improvement of best-corrected visual acuity was seen in 8 of 10 patients. Rebleed was seen in 2 eyes that were retreated with intravitreal injection of recombinant tissue plasminogen activator, bevacizumab, and 20% SF6 gas. CONCLUSIONS: This modified technique aids in the effective displacement of thick submacular hemorrhage with simultaneous treatment of the underlying choroidal neovascular membrane, which halts the disease progression resulting in significant improvement of visual acuity.
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Hemorragia Retiniana/cirugía , Vitrectomía/métodos , Degeneración Macular Húmeda/complicaciones , Anciano , Anciano de 80 o más Años , Aire , Inhibidores de la Angiogénesis/uso terapéutico , Bevacizumab/uso terapéutico , Terapia Combinada , Femenino , Fibrinolíticos/administración & dosificación , Humanos , Inyecciones Intravítreas , Masculino , Persona de Mediana Edad , Posición Prona , Hemorragia Retiniana/tratamiento farmacológico , Hemorragia Retiniana/etiología , Estudios Retrospectivos , Activador de Tejido Plasminógeno/administración & dosificación , Agudeza Visual , Degeneración Macular Húmeda/tratamiento farmacológico , Degeneración Macular Húmeda/cirugíaRESUMEN
PURPOSE: To analyze type 1 neovascular membranes in age-related macular degeneration (AMD) using optical coherence tomography (OCT) angiography, to correlate morphologic characteristics with imaging and clinical criteria, and to analyze structural features of type 1 neovascularization sequentially after anti-vascular endothelial growth factor (VEGF) therapy. DESIGN: Prospective interventional case series. METHODS: Macular OCT angiography images were acquired using the RTVue XR Avanti with AngioVue. Distinct morphologic patterns and quantifiable features of the neovascular membranes were studied on en face projection images at baseline and follow-up. RESULTS: Thirty-three eyes of 25 patients were included. In 75% of the eyes, a highly organized vascular complex could be identified. A large main central vessel trunk/feeder vessel could be seen in 72% of these eyes, with vessels radiating in a branching pattern either in all directions from the center of the lesion ("medusa" pattern), or from one side of the lesion ("seafan" pattern). Of the 18 eyes with follow-up OCT angiography, the lesion area and vessel density remained unchanged, even after anti-vascular endothelial growth factor (VEGF) therapy, indicating a more mature longstanding neovascular complex resistant to anti-VEGF therapy. CONCLUSIONS: OCT angiography provides a unique opportunity to study the morphology of occult type 1 neovascular membranes in AMD and allows precise structural and vascular assessment noninvasively. We identified a large mature neovascular complex in approximately 75% of eyes, typically consisting of a feeder vessel and large branching vessels resistant to anti-VEGF therapy. OCT angiography may better guide evaluation and treatment of neovascular AMD, and may contribute to the development of improved therapies.
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Inhibidores de la Angiogénesis/uso terapéutico , Angiografía con Fluoresceína , Neovascularización Retiniana/diagnóstico , Tomografía de Coherencia Óptica , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Degeneración Macular Húmeda/diagnóstico , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inyecciones Intravítreas , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Ranibizumab/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Desprendimiento de Retina/patología , Neovascularización Retiniana/tratamiento farmacológico , Epitelio Pigmentado de la Retina/patología , Líquido Subretiniano , Agudeza Visual/fisiología , Degeneración Macular Húmeda/tratamiento farmacológicoRESUMEN
Jalili syndrome (JS) (MIM#217080) is a rare genetic disorder characterized by the comorbid appearance of cone-rod dystrophy (CORD) and amelogenesis imperfecta (AI). JS is an autosomal recessive inherited disorder caused by different mutations, all with a linkage at achromatopsia locus 2 q11 on the metal transporter gene CNNM4. The case report presented here describes JS with distinct phenotypic variations such as situs inversus totalis (SIT) along with additional ophthalmic findings such as keratoconus and ectopia lentis. It is the first case of JS reported from the Indian subcontinent, affecting a male patient of Muslim faith from an area having high fluoride levels in the ground water. A positive history of consanguineous marriage among his family members of past generations was also evident.