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1.
Ophthalmology ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38336283

RESUMO

TOPIC: This systematic review and meta-analysis aims to clarify the association of cataract surgery with cognitive impairment and dementia. CLINICAL RELEVANCE: The association between vision impairment and cognitive decline is well-established. However, the cognitive benefits of cataract surgery are less clear. Given the lack of cure for dementia, identifying modifiable risk factors is key in caring for patients with cognitive deficits. METHODS: The study was conducted following Preferred Reporting Items for Systematic Review and Meta-analyses guidelines. PubMed, Embase, and Cochrane Library were searched from inception through October 11, 2022, for studies reporting the effect of cataract surgery on cognitive impairment and dementia. We pooled maximally adjusted hazard ratios (HRs) for dichotomous outcomes and ratio of means (RoM) for continuous outcomes using a random-effects model. Heterogeneity was examined using sensitivity and subgroup analyses. The quality of evidence was evaluated using the Newcastle-Ottawa scale, Cochrane risk-of-bias tool for randomized trials, and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines. RESULTS: This review included 24 articles comprising 558 276 participants, of which 19 articles were analyzed qualitatively. The bias of studies ranged from low to moderate, and GRADE extended from very low to low. Cataract surgery was associated with a 25% reduced risk of long-term cognitive decline compared with those with uncorrected cataracts (HR, 0.75; 95% confidence interval [CI], 0.72-0.78). This cognitive benefit was seen across various cognitive outcomes and remained robust to sensitivity analyses. Participants who underwent cataract surgery showed a similar risk of long-term cognitive decline as healthy controls without cataracts (HR, 0.84; 95% CI, 0.66-1.06). Additionally, cataract surgery was associated with a 4% improvement in short-term cognitive test scores among participants with normal cognition (RoM, 0.96; 95% CI, 0.94-0.99), but no significant association was observed among participants with preexisting cognitive impairment. DISCUSSION: Cataract surgery may be associated with a lower risk of cognitive impairment and dementia, and cataract-associated vision impairment may be a modifiable risk factor for cognitive decline. Physicians should be aware of the cognitive sequelae of cataracts and the possible benefits of surgery. The cognitive benefits of cataract surgery should be investigated further in randomized trials. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

2.
Retina ; 43(11): 1945-1950, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37339455

RESUMO

BACKGROUND/PURPOSE: To evaluate clinical outcomes and assess genotype-phenotype correlations in patients with familial exudative vitreoretinopathy (FEVR). METHODS: Clinical charts of 40 patients with FEVR were reviewed. FEVR was staged per Pendergast and Trese, and retinal dragging and folds further classified per Yaguchi et al. We performed whole-exome sequencing and compared clinical characteristics between genetic-positive and genetic-negative groups. RESULTS: The mean duration of follow-up was 5.4 years (range: 0.33, 15) for genetic-positive and 6.9 (range: 1, 20) for genetic-negative patients. The mean age at diagnosis was 5.6 years (0.25, 27) for genetic-positive and 6.0 (0, 32) for genetic-negative patients. Genetic-positive patients reported 100% full-term births and genetic-negative patients reported 45% full-term births ( P = 0.0012). There were more patients with retinal folds with all major vessels affected (Yaguchi's Group 4) in genetic-positive compared with genetic-negative patients (21.4% vs. 2.6%, P = 0.045). TSPAN12 was the most common (57.1%) genetic mutation in our population of which 50% exhibited asymmetric presentation. CONCLUSION: Patients who test positive for a typical FEVR gene mutation reported more term births and had more severe disease by Yaguchi's classification. TSPAN12 was the most common genetic mutation in our population and had highly asymmetrical disease.


Assuntos
Oftalmopatias Hereditárias , Doenças Retinianas , Humanos , Vitreorretinopatias Exsudativas Familiares/diagnóstico , Centros de Atenção Terciária , Fenótipo , Tetraspaninas/genética , Linhagem , Doenças Retinianas/diagnóstico , Doenças Retinianas/genética , Mutação , Estudos de Associação Genética , Análise Mutacional de DNA , Oftalmopatias Hereditárias/genética
3.
Retina ; 40(11): 2184-2190, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31842192

RESUMO

PURPOSE: To examine the relationship between macular microvasculature parameters and functional changes in persons with diabetic retinopathy (DR). METHODS: Cross-sectional study of 76 eyes with varying levels of DR. Optical coherence tomography angiography (OCTA) quantified superficial and deep perifoveal vessel densities and foveal avascular zone areas. Retinal sensitivity was measured using microperimetry. Optical coherence tomography angiography parameters and retinal sensitivity were correlated. RESULTS: Deep perifoveal vessel density decreased with increasing severity of DR (adjusted mean 51.93 vs. 49.89 vs. 47.96, P-trend = 0.005). Superficial and deep foveal avascular zone area increased with increasing DR severity (adjusted mean: 235.0 µm vs. 303.4 µm vs. 400.9 µm, P-trend = 0.003 [superficial]; 333.1 µm vs. 513.3 µm vs. 530.2 µm, P-trend = 0.001 [deep]). Retinal sensitivity decreased with increasing DR severity (adjusted mean: 25.12 dB vs. 22.34 dB vs. 20.67 dB, P-trend = 0.003). Retinal sensitivity correlated positively with deep perifoveal vessel density (Pearson's ρ = 0.276, P = 0.020) and inversely with superficial foveal avascular zone area (Pearson's ρ = -0.333, P = 0.010). CONCLUSION: Alterations in retinal microvasculature can be observed with OCTA with increasing severity of DR. These changes are correlated with reduced retinal sensitivity. Optical coherence tomography angiography is useful to detect and quantify the microvasculature properties of eyes with diabetic macular ischemia.


Assuntos
Retinopatia Diabética/fisiopatologia , Isquemia/diagnóstico , Vasos Retinianos/fisiopatologia , Idoso , Estudos Transversais , Diabetes Mellitus Tipo 2/fisiopatologia , Retinopatia Diabética/diagnóstico por imagem , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Testes de Campo Visual
4.
Retina ; 39(9): 1751-1760, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30015760

RESUMO

PURPOSE: To evaluate the clinical characteristics and surgical outcomes of pediatric retinal detachments (RDs) in an Asian population. METHODS: Retrospective review of 171 eyes of 152 pediatric patients with rhegmatogenous RD over a 20-year period. RESULTS: Myopia was the most common risk factor in our population. At 6 months, primary anatomical success was 60.7%, and overall anatomical success was 86.7%. A total of 46.8% had best-corrected visual acuity of 20/40 or better, and 81.6% had best-corrected visual acuity of 20/200 or better. In primary RDs, high myopia (≤-6D) patients had a lower primary anatomical success compared to patients with moderate myopia (≤-2D) (59.3 vs. 100% P = 0.03). Increasing age and absence of proliferative vitreoretinopathy were associated with anatomical and visual success. Pars plana vitrectomy as the primary procedure was associated with decreased odds of anatomical success. A longer duration of symptoms, cataract, and a larger RD extent were associated with poorer functional outcome. CONCLUSION: Myopia was the commonest risk factor for pediatric RD in our population. Good anatomical and functional outcome can be achieved with surgery. Increasing age at presentation and absence of proliferative vitreoretinopathy was associated with anatomical and functional success. High myopia was associated with poorer anatomical and functional outcome.


Assuntos
Miopia/cirurgia , Descolamento Retiniano/cirurgia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Miopia/diagnóstico por imagem , Miopia/etnologia , Prevalência , Reoperação/estatística & dados numéricos , Descolamento Retiniano/diagnóstico por imagem , Descolamento Retiniano/etnologia , Estudos Retrospectivos , Singapura/epidemiologia , Resultado do Tratamento , Acuidade Visual/fisiologia , Vitrectomia/estatística & dados numéricos , Vitreorretinopatia Proliferativa/complicações , Vitreorretinopatia Proliferativa/etnologia
5.
Ophthalmol Retina ; 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38280425

RESUMO

OBJECTIVE: To review recent technological advancement in imaging, surgical visualization, robotics technology, and the use of artificial intelligence in surgical vitreoretinal (VR) diseases. BACKGROUND: Technological advancements in imaging enhance both preoperative and intraoperative management of surgical VR diseases. Widefield imaging in fundal photography and OCT can improve assessment of peripheral retinal disorders such as retinal detachments, degeneration, and tumors. OCT angiography provides a rapid and noninvasive imaging of the retinal and choroidal vasculature. Surgical visualization has also improved with intraoperative OCT providing a detailed real-time assessment of retinal layers to guide surgical decisions. Heads-up display and head-mounted display utilize 3-dimensional technology to provide surgeons with enhanced visual guidance and improved ergonomics during surgery. Intraocular robotics technology allows for greater surgical precision and is shown to be useful in retinal vein cannulation and subretinal drug delivery. In addition, deep learning techniques leverage on diverse data including widefield retinal photography and OCT for better predictive accuracy in classification, segmentation, and prognostication of many surgical VR diseases. CONCLUSION: This review article summarized the latest updates in these areas and highlights the importance of continuous innovation and improvement in technology within the field. These advancements have the potential to reshape management of surgical VR diseases in the very near future and to ultimately improve patient care. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

6.
Diagnostics (Basel) ; 13(8)2023 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-37189561

RESUMO

Indirect ophthalmoscopy and handheld retinal imaging are the most common and traditional modalities for the evaluation and documentation of the pediatric fundus, especially for pre-verbal children. Optical coherence tomography (OCT) allows for in vivo visualization that resembles histology, and optical coherence tomography angiography (OCTA) allows for non-invasive depth-resolved imaging of the retinal vasculature. Both OCT and OCTA were extensively used and studied in adults, but not in children. The advent of prototype handheld OCT and OCTA have allowed for detailed imaging in younger infants and even neonates in the neonatal care intensive unit with retinopathy of prematurity (ROP). In this review, we discuss the use of OCTA and OCTA in various pediatric retinal diseases, including ROP, familial exudative vitreoretinopathy (FEVR), Coats disease and other less common diseases. For example, handheld portable OCT was shown to detect subclinical macular edema and incomplete foveal development in ROP, as well as subretinal exudation and fibrosis in Coats disease. Some challenges in the pediatric age group include the lack of a normative database and the difficulty in image registration for longitudinal comparison. We believe that technological improvements in the use of OCT and OCTA will improve our understanding and care of pediatric retina patients in the future.

7.
JAMA Ophthalmol ; 141(6): 582-588, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37166816

RESUMO

Importance: Retinopathy of prematurity (ROP) telemedicine screening programs have been found to be effective, but they rely on widefield digital fundus imaging (WDFI) cameras, which are expensive, making them less accessible in low- to middle-income countries. Cheaper, smartphone-based fundus imaging (SBFI) systems have been described, but these have a narrower field of view (FOV) and have not been tested in a real-world, operational telemedicine setting. Objective: To assess the efficacy of SBFI systems compared with WDFI when used by technicians for ROP screening with both artificial intelligence (AI) and human graders. Design, Setting, and Participants: This prospective cross-sectional comparison study took place as a single-center ROP teleophthalmology program in India from January 2021 to April 2022. Premature infants who met normal ROP screening criteria and enrolled in the teleophthalmology screening program were included. Those who had already been treated for ROP were excluded. Exposures: All participants had WDFI images and from 1 of 2 SBFI devices, the Make-In-India (MII) Retcam or Keeler Monocular Indirect Ophthalmoscope (MIO) devices. Two masked readers evaluated zone, stage, plus, and vascular severity scores (VSS, from 1-9) in all images. Smartphone images were then stratified by patient into training (70%), validation (10%), and test (20%) data sets and used to train a ResNet18 deep learning architecture for binary classification of normal vs preplus or plus disease, which was then used for patient-level predictions of referral warranted (RW)- and treatment requiring (TR)-ROP. Main Outcome and Measures: Sensitivity and specificity of detection of RW-ROP, and TR-ROP by both human graders and an AI system and area under the receiver operating characteristic curve (AUC) of grader-assigned VSS. Sensitivity and specificity were compared between the 2 SBFI systems using Pearson χ2testing. Results: A total of 156 infants (312 eyes; mean [SD] gestational age, 33.0 [3.0] weeks; 75 [48%] female) were included with paired examinations. Sensitivity and specificity were not found to be statistically different between the 2 SBFI systems. Human graders were effective with SBFI at detecting TR-ROP with a sensitivity of 100% and specificity of 83.49%. The AUCs with grader-assigned VSS only were 0.95 (95% CI, 0.91-0.99) and 0.96 (95% CI, 0.93-0.99) for RW-ROP and TR-ROP, respectively. For the AI system, the sensitivity of detecting TR-ROP sensitivity was 100% with specificity of 58.6%, and RW-ROP sensitivity was 80.0% with specificity of 59.3%. Conclusions and Relevance: In this cross-sectional study, 2 different SBFI systems used by technicians in an ROP screening program were highly sensitive for TR-ROP. SBFI systems with AI may be a cost-effective method to improve the global capacity for ROP screening.


Assuntos
Oftalmologia , Retinopatia da Prematuridade , Telemedicina , Recém-Nascido , Lactente , Humanos , Feminino , Adulto , Masculino , Estudos Transversais , Retinopatia da Prematuridade/diagnóstico , Estudos Prospectivos , Smartphone , Inteligência Artificial , Telemedicina/métodos , Recém-Nascido Prematuro , Idade Gestacional , Sensibilidade e Especificidade , Oftalmoscopia/métodos
8.
Clin Exp Ophthalmol ; 40(3): 295-304, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21718413

RESUMO

This paper aims to review the current methods available for the measurement of intraocular pressure after myopic laser in situ keratomileusis for the correction of myopia. Searches were performed for studies that assessed or compared various methods of intraocular pressure assessment. There were 20 eligible studies that explored the use of pneumotonometry, pressure phosphene tonometry, rebound tonometry, dynamic contour tonometry, statistical modeling, mathematical formulae, ocular response analyzer and even measuring intraocular pressure on the nasal cornea. Our review shows that an ideal method would be one that is independent of corneal factors. Dynamic contour tonometry and pressure phosphene tonometry held promise in research settings. More studies need to be done to validate the new methods of intraocular pressure assessment, especially in glaucoma patients. It is important to empower laser in situ keratomileusis patients with knowledge of these difficulties and potential implications for the future.


Assuntos
Glaucoma de Ângulo Aberto/diagnóstico , Pressão Intraocular/fisiologia , Ceratomileuse Assistida por Excimer Laser In Situ , Lasers de Excimer , Miopia/cirurgia , Tonometria Ocular/métodos , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Miopia/fisiopatologia , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Tonometria Ocular/instrumentação
9.
Antibiotics (Basel) ; 11(11)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36358140

RESUMO

Staphylococcus lugdunensis endophthalmitis is an uncommon intraocular infection with potentially visually devastating consequences. S. lugdunensis endophthalmitis have been reported following cataract surgery, trauma, intravitreal injections of anti-vascular endothelial growth factor agents and dexamethasone implant. We report four cases of postoperative S. lugdunensis endophthalmitis after cataract extraction (three patients) and combined pars plana vitrectomy and cataract extraction (one patient). The onset of presentation of endophthalmitis was acute (within 2 weeks) in two patients, subacute (2 to 6 weeks) in one patient, and chronic (more than 6 weeks) in one patient. All patients had presenting visual acuity (VA) of hand motions or worse and were treated with pars plana vitrectomy with intravitreal antibiotics. The final VA was 20/50 in two patients, 4/200 in one patient with pre-existing myopic maculopathy, and no light perception in one patient with retinal detachment. In antibiotic susceptibility testing, S. lugdunensis isolates were resistant to penicillin (3/4, 75%), but all were susceptible to vancomycin, oxacillin, teicoplanin, tigecycline, and sulfamethoxazole-trimethoprim. S. lugdunensis may be associated with acute or chronic endophthalmitis. Favorable visual outcomes can be achieved with prompt diagnosis and management.

10.
Asia Pac J Ophthalmol (Phila) ; 11(5): 434-440, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36102646

RESUMO

PURPOSE: To describe ophthalmology training experiences across the Asia-Pacific (APAC). DESIGN: Survey study. METHODS: We utilized an anonymous online survey, which was previously validated and conducted in Europe, through Young Ophthalmologist leaders from the national member societies of the Asia-Pacific Academy of Ophthalmology (APAO) from September 2019 to July 2021. Responses were based on a 5-point Likert scale (where applicable) and data were analyzed using Microsoft Excel. Our main outcome measures were differences between regions, that is, Southeast Asia (SEA) and Western Pacific (WP); and seniority, that is, trainees/junior ophthalmologists and senior ophthalmologists. RESULTS: We collated 130 responses representing 20 regions in the APAC region. The year of completion of ophthalmic training ranged from 1999 to 2024. The mean duration of training was 3.7±1.0 years. Most (98/130, 75%) indicated an interest for a common training standard across the APAC. Comparing SEA and WP trainees, both regions had similar working environments, but those in SEA reported significantly lower remuneration than their counterparts in WP ($600 vs $3000, P <0.05). WP trainees performed more phacoemulsification surgeries (76 WP vs 19 SEA), while SEA trainees conducted more manual small incision cataract surgeries (157 WP vs 1.5 SEA per duration of training). Senior ophthalmologists performed more cataract surgeries (210.9 senior ophthalmologists vs 40.1 junior ophthalmologists). Trainees had less confidence in medical competency areas such as interpreting an electroretinogram/visual evoked potential/electrooculogram (SEA=1.8, WP=2.1) and conducting an angiography (SEA=2.8, WP=3.4). CONCLUSIONS: Our study highlighted heterogeneity among ophthalmology training experiences in the APAC region, with the majority indicating an interest in a common training standard.


Assuntos
Catarata , Oftalmopatias , Internato e Residência , Oftalmologistas , Oftalmologia , Competência Clínica , Educação de Pós-Graduação em Medicina , Potenciais Evocados Visuais , Oftalmopatias/cirurgia , Humanos , Oftalmologistas/educação , Oftalmologia/educação
11.
J Vitreoretin Dis ; 5(3): 266-269, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-37006517

RESUMO

Purpose: We present imaging features of retinal detachment (RD) and secondary epiretinal membrane in a case of an inadvertent globe penetration following preoperative peribulbar anesthesia. Methods: A 60-year-old woman was referred for a localized RD and epiretinal membrane following uneventful cataract surgery. Widefield fundus photography and optical coherence tomography were used to assess and record the pathology. The current literature was reviewed. Results: Full-thickness breaks were noted in the neurosensory retina extending into the scleral wall. Vertical tracks were noted in the inferotemporal quadrant of the eye. The patient underwent trans pars plana vitrectomy, membrane peel, and gas. Her 1-month postoperative visual acuity was 20/30. Conclusions: Globe penetration with RD is a rare but potentially sight-threatening complication of peribulbar anesthesia. Diagnosis can be challenging because of the infrequency of occurrence and delays in presentation. A high index of suspicion is key alongside consideration of other likely differentials.

12.
Invest Ophthalmol Vis Sci ; 62(1): 9, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33404598

RESUMO

Purpose: To prospectively evaluate whether diabetic macular ischemia detected with coherence tomography angiography (OCTA) is associated with change in functional outcomes over a period of one year. Methods: This is a one-year prospective, observational study that included 56 eyes with varying levels of diabetic retinopathy. All participants underwent best corrected visual acuity evaluation, swept-source OCTA and microperimetry at baseline and repeated at one year. Parafoveal vessel densities (VD) and foveal avascular zone (FAZ) areas were generated from OCTA in the superficial and deep vascular plexuses. The influence of baseline and change in OCTA parameters on change in visual acuity and retinal sensitivity over one year was evaluated. Results: Over the one-year follow-up period, 16% (9) of eyes had at least one line worsening in BCVA and 7% (4) of eyes had at least 5% decrease in retinal sensitivity compared to baseline. Diabetic retinopathy progressed in 12.5%. Mean superficial vascular plexus (SVP) FAZ area increased (0.32 ± 0.15 to 0.39 ± 0.18 mm2, P = 0.003) and parafoveal VD in deep vascular plexus (DVP) decreased (49.8 ± 3.7% to 48.8 ± 2.9%, P = 0.040) at one year compared to baseline. In the multivariate regression analysis, larger baseline DVP FAZ area was associated with worsening of BCVA over one year (ß = 0.16 logMAR per mm2, 95% CI 0.02 to 0.31, P = 0.032). In addition, larger decreases in SVP VD (ß = -4.18 db per 10% decrease, 95% CI -6.55 to -1.80, P = 0.002) was associated with worsening of retinal sensitivity over one year. Conclusions: Progression of parafoveal microvasculature changes over one year can be detected using OCTA. Larger baseline DVP FAZ area on OCTA is predictive of worsening in visual outcomes, and larger decreases in SVP VD were associated with worsening of retinal sensitivity over a course of one year in diabetic individuals.


Assuntos
Retinopatia Diabética/fisiopatologia , Angiofluoresceinografia , Isquemia/fisiopatologia , Retina/fisiopatologia , Vasos Retinianos/fisiopatologia , Tomografia de Coerência Óptica , Idoso , Diabetes Mellitus Tipo 2/fisiopatologia , Retinopatia Diabética/diagnóstico , Feminino , Seguimentos , Humanos , Isquemia/diagnóstico , Masculino , Microvasos/fisiopatologia , Pessoa de Meia-Idade , Estudos Prospectivos , Retina/diagnóstico por imagem , Vasos Retinianos/diagnóstico por imagem , Acuidade Visual/fisiologia , Testes de Campo Visual , Campos Visuais/fisiologia
13.
J Pediatr Ophthalmol Strabismus ; 58(4): 261-269, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34288773

RESUMO

The rising prevalence of retinopathy of prematurity (ROP) in low- and middle-income countries has increased the need for screening at-risk infants. The purpose of this article was to review the impact of tele-medicine and technology on ROP screening programs. Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was performed using PubMed, Pro-Quest, and Google Scholar bibliographic search engine. Terms searched included retinopathy of prematurity, telemedicine, and tele-ophthalmology. Data regarding internet access and gross domestic product per capita were obtained from the World Bank. Information was also obtained about internet access, speeds, and costs in low-income countries. There has been increasing integration of telemedicine and technology for ROP screening and management. Low-income countries are using available internet options and information and communications technology for ROP screening, which can aid in addressing the unique challenges faced by low-income countries. This provides a promising solution to the third epidemic of ROP by expanding and improving screening and management. Although telemedicine systems may serve as a cost-effective approach to facilitate delivery of health care, programs (especially in lowand middle-income countries) require national support to maintain its infrastructure. [J Pediatr Ophthalmol Strabismus. 2021;58(4):261-269.].


Assuntos
Epidemias , Oftalmologia , Retinopatia da Prematuridade , Telemedicina , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/epidemiologia
14.
Stem Cell Res Ther ; 12(1): 423, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315534

RESUMO

BACKGROUND: Human pluripotent stem cells (hPSCs) provide a promising cell source for retinal cell replacement therapy but often lack standardized cell production and live-cell shipment logistics as well as rigorous analyses of surgical procedures for cell transplantation in the delicate macula area. We have previously established a xeno- and feeder cell-free production system for hPSC differentiated retinal pigment epithelial (RPE) cells, and herein, a novel immunosuppressed non-human primate (NHP) model with a disrupted ocular immune privilege is presented for transplanting human embryonic stem cell (hESC)-derived RPE on a scaffold, and the safety and submacular graft integration are assessed. Furthermore, the feasibility of intercontinental shipment of live hESC-RPE is examined. METHODS: Cynomolgus monkeys were systemically immunosuppressed and implanted with a hESC-RPE monolayer on a permeable polyester-terephthalate (PET) scaffold. Microscope-integrated intraoperative optical coherence tomography (miOCT)-guided surgery, postoperative follow-up incorporated scanning laser ophthalmoscopy, spectral domain (SD-) OCT, and full-field electroretinography (ERG) were used as outcome measures. In addition, histology was performed after a 28-day follow-up. RESULTS: Intercontinental cell shipment, which took >30 h from the manufacturing to the transplantation site, did not alter the hESC-RPE quality. The submacular hESC-RPE xenotransplantation was performed in 11 macaques. The miOCT typically revealed foveal disruption. ERG showed amplitude and peak time preservation in cases with favorable surgical outcomes. Histology confirmed photoreceptor preservation above the grafts and in vivo phagocytosis by hESC-RPE, albeit evidence of cytoplasmic redistribution of opsin in photoreceptors and glia hypertrophy. The immunosuppression protocol efficiently suppressed retinal T cell infiltration and microglia activation. CONCLUSION: These results suggest both structural and functional submacular integrations of hESC-RPE xenografts. It is anticipated that surgical technique refinement will further improve the engraftment of macular cell therapeutics with significant translational relevance to improve future clinical trials.


Assuntos
Células-Tronco Embrionárias Humanas , Animais , Diferenciação Celular , Linhagem Celular , Xenoenxertos , Humanos , Primatas , Epitélio Pigmentado da Retina , Transplante Heterólogo
15.
Invest Ophthalmol Vis Sci ; 62(7): 7, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34096974

RESUMO

Purpose: The purpose of this study was to assess whether the tractional elements of pathologic myopia (PM; e.g. myopic traction maculopathy [MTM], posterior staphyloma [PS], and aberrant posterior vitreous detachment [PVD]) are associated with myopic macular degeneration (MMD) independent of age and axial length, among highly myopic (HM) eyes. Methods: One hundred twenty-nine individuals with 239 HM eyes from the Myopic and Pathologic Eyes in Singapore (MyoPES) cohort underwent ocular biometry, fundus photography, swept-source optical coherence tomography, and ocular B-scan ultrasound. Images were analyzed for PVD grade, and presence of MTM, PS, and MMD. The χ² test was done to determine the difference in prevalence of MMD between eyes with and without PVD, PS, and MTM. Multivariate probit regression analyses were performed to ascertain the relationship between the potential predictors (PVD, PS, and MTM) and outcome variable (MMD), after accounting for possible confounders (e.g. age and axial length). Marginal effects were reported. Results: Controlling for potential confounders, eyes with MTM have a 29.92 percentage point higher likelihood of having MMD (P = 0.003), and eyes with PS have a 25.72 percentage point higher likelihood of having MMD (P = 0.002). The likelihood of MMD increases by 10.61 percentage points per 1 mm increase in axial length (P < 0.001). Subanalysis revealed that eyes with incomplete PVD have a 22.54 percentage point higher likelihood of having MMD than eyes with early PVD (P = 0.04). Conclusions: Our study demonstrated an association between tractional (MTM, PS, and persistently incomplete PVD) and degenerative elements of PM independent of age and axial length. These data provide further insights into the pathogenesis of MMD.


Assuntos
Comprimento Axial do Olho , Degeneração Macular , Miopia Degenerativa , Descolamento do Vítreo , Comprimento Axial do Olho/diagnóstico por imagem , Comprimento Axial do Olho/fisiopatologia , Causalidade , Progressão da Doença , Feminino , Humanos , Degeneração Macular/complicações , Degeneração Macular/diagnóstico , Degeneração Macular/epidemiologia , Degeneração Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Miopia Degenerativa/complicações , Miopia Degenerativa/diagnóstico , Miopia Degenerativa/fisiopatologia , Oftalmoscopia/métodos , Gravidade do Paciente , Índice de Gravidade de Doença , Singapura/epidemiologia , Tomografia de Coerência Óptica/métodos , Ultrassonografia/métodos , Descolamento do Vítreo/diagnóstico , Descolamento do Vítreo/etiologia , Descolamento do Vítreo/fisiopatologia
16.
Front Genet ; 12: 794805, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35069693

RESUMO

Inherited retinal diseases (IRDs) are a heterogenous group of orphan eye diseases that typically result from monogenic mutations and are considered attractive targets for gene-based therapeutics. Following the approval of an IRD gene replacement therapy for Leber's congenital amaurosis due to RPE65 mutations, there has been an intensive international research effort to identify the optimal gene therapy approaches for a range of IRDs and many are now undergoing clinical trials. In this review we explore therapeutic challenges posed by IRDs and review current and future approaches that may be applicable to different subsets of IRD mutations. Emphasis is placed on five distinct approaches to gene-based therapy that have potential to treat the full spectrum of IRDs: 1) gene replacement using adeno-associated virus (AAV) and nonviral delivery vectors, 2) genome editing via the CRISPR/Cas9 system, 3) RNA editing by endogenous and exogenous ADAR, 4) mRNA targeting with antisense oligonucleotides for gene knockdown and splicing modification, and 5) optogenetic approaches that aim to replace the function of native retinal photoreceptors by engineering other retinal cell types to become capable of phototransduction.

17.
Sci Rep ; 10(1): 5474, 2020 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-32214123

RESUMO

To describe the 25-year surgical trends, long-term outcomes and risk factors affecting the outcomes of giant retinal tear-related rhegmatogenous retinal detachments (GRT-RRD). Patients' demographics, pre-operative characteristics, risk factors, operative procedures and post-operative outcomes were collected and divided into three groups - Group A: 1991 to 2015 (overall); Group B: 1991 to 2005, and Group C: 2006 to 2015. Functional and anatomical successes were monitored over a 5-year period. Multivariate logistic regression analysis was performed to identify the risk factors related to functional and anatomical success.127 eyes of 127 patients were included in the study. At 5th year, 69.4% patients had visual acuity (VA) < logMAR 1.0 with 87.5% primary anatomical success rate. While the functional outcome remained the same between group B and C, there was an increase in the anatomical success from 89.7% to 100%, albeit not statistically significant. Patients with worse presenting VA, 150 degrees or more of giant retina tear, macula-detached status and presence of PVR were associated with VA of> logMAR 1.0 (all p < 0.05). The types of surgery (TPPV vs combined SB/TPPV), number of breaks, lens extraction and additional cryotherapy were not associated with the functional or anatomical success. In conclusion, the GRT-RRD functional and structural outcomes were comparable between 1991-2005 and 2006-2015, albeit a statistically insignificant improvement of anatomical outcome over the past 25 years. Worse presenting VA, 150 degrees or more of giant retinal tear, detached macula and presence of PVR were associated with poorer visual outcome.


Assuntos
Descolamento Retiniano/cirurgia , Perfurações Retinianas/cirurgia , Estudos de Coortes , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Recidiva , Análise de Regressão , Descolamento Retiniano/fisiopatologia , Perfurações Retinianas/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Recurvamento da Esclera/métodos , Fatores de Tempo , Resultado do Tratamento , Acuidade Visual , Vitrectomia/métodos , Vitreorretinopatia Proliferativa/etiologia
18.
Ophthalmic Plast Reconstr Surg ; 24(6): 486-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19033851

RESUMO

The authors report a case of bilateral orbital varices in a 19-year-old man with a 7-year history of intermittent left proptosis and dystopia. CT demonstrated enhancing lesions with phleboliths and gadolinium-enhanced MRI showed characteristic hyperintense lesions. The asymptomatic right lesion was treated conservatively; the left lesion was excised following intralesional injection of cyanoacrylate. Bilaterality in orbital varices may not be obvious clinically and only diagnosed radiologically. A multidisciplinary approach involving the ophthalmologist and interventional radiologist using intraoperative fluoroscopy enabled accurate characterization, delineation, embolizationm, and excision of the lesion with good hemostatic control.


Assuntos
Quimioembolização Terapêutica/métodos , Procedimentos Cirúrgicos Oftalmológicos/métodos , Órbita/irrigação sanguínea , Varizes/terapia , Diagnóstico Diferencial , Seguimentos , Humanos , Angiografia por Ressonância Magnética , Masculino , Flebografia , Tomografia Computadorizada por Raios X , Varizes/diagnóstico , Adulto Jovem
19.
Orbit ; 27(3): 231-3, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18569837

RESUMO

Epibulbar osseous choristoma occurs rarely and is commonly mistaken for a dermoid or dermolipoma. We report two cases: an 8-year-old boy and a 79-year-old lady with epibulbar osseous choristomas where computed tomography showed an extraocular lesion in the temporal quadrant and diagnosis was confirmed by excision biopsy. The osseous component was adherent to the sclera in the young patient, while it was loosely attached to the surrounding tissue in the older patient. We believe that the 79-year-old lady is the oldest reported patient with an epibulbar osseous choristoma.


Assuntos
Osso e Ossos , Coristoma/diagnóstico , Doenças da Túnica Conjuntiva/diagnóstico , Idoso , Biópsia por Agulha , Criança , Coristoma/patologia , Doenças da Túnica Conjuntiva/patologia , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Tomografia Computadorizada por Raios X
20.
Surv Ophthalmol ; 62(4): 462-492, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28189495

RESUMO

Retinal angiomatous proliferation (RAP) is a unique variant of neovascular age-related macular degeneration. Published studies have estimated that up to 15% of patients with neovascular age-related macular degeneration have RAP. Clinical features frequently associated with RAP include bilateral disease, presence of pigment epithelial detachments, and reticular pseudodrusen. RAP is more frequently associated with the development of retinal pigment epithelial tears and geographic atrophy that can lead to severe vision loss. Recent advances in retinal and choroidal imaging technology have furthered our understanding of RAP. Although indocyanine green angiography remains the gold standard diagnostic tool, optical coherence tomography has improved the precision by which neovascular age-related macular degeneration with RAP lesions can be diagnosed, staged, and monitored. Anti-vascular endothelial growth factor therapy is currently the first line of treatment. Other treatment options including combination of photodynamic therapy with antiangiogenic agent intravitreal injections or corticosteroids may also achieve a reasonable therapeutic outcome; however, RAP may portend a more guarded visual prognosis than typical choroidal neovascularization because of variable treatment response and dependence on the disease stage. Future basic and clinical research is needed to clarify the pathophysiology, definition and classification, optimal treatment regimen, and long-term outcome of RAP.


Assuntos
Angiofluoresceinografia/métodos , Retina/patologia , Neovascularização Retiniana , Tomografia de Coerência Óptica/métodos , Fundo de Olho , Saúde Global , Humanos , Incidência , Neovascularização Retiniana/classificação , Neovascularização Retiniana/diagnóstico , Neovascularização Retiniana/epidemiologia
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