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PURPOSE: To report two cases masquerading as TORCH but eventually diagnosed with Enhanced S-cone Syndrome (ESCS). METHODS: Descriptive case report. RESULTS: Case 1: A ten-month-old boy presented with high hypermetropia, strabismus and bilateral chorioretinal pigmented scars with a history of cat scratch of his mother during pregnancy. He was treated for suspected toxoplasma retinitis. Choroidal neovascular membranes (CNV) were diagnosed bilaterally and treated with intravitreal bevacizumab. Genetic testing showed homozygote mutation in NR2E3 gene. Case 2: A two-year old girl presented with bilateral high hypermetropia and strabismus. Funduscopy revealed extrafoveal chorioretinal lesions and surrounding subretinal fibrosis. An elevated titer of anti-toxocara IgG antibodies was detected and managed accordingly. LE CNV was diagnosed and treated with intravitreal bevacizumab. Genetic testing disclosed homozygote mutation in NR2E3. CONCLUSION: Ocular manifestations in ESCS can be reminiscent to TORCH. CNV may develop with an incidence of 15%. We report the youngest patient with ESCS-associated CNV.
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Neovascularização de Coroide , Hiperopia , Masculino , Humanos , Bevacizumab/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Hiperopia/complicações , Hiperopia/tratamento farmacológico , Angiofluoresceinografia , Neovascularização de Coroide/diagnóstico , Injeções Intravítreas , Tomografia de Coerência ÓpticaRESUMO
AIM: To analyze the risk factors, ophthalmological features, treatment modalities and their effect on the visual outcome in patients with endogenous fungal endophthalmitis (EFE). METHODS: Data retrieved from the medical files included age at presentation to the uveitis clinic, gender, ocular symptoms and their duration before presentation, history of fever, eye affected, anatomical diagnosis and laboratory evidence of fungal infection. Medical therapy recorded included systemic antifungal therapy and its duration, use of intravitreal antifungal agents and use of oral/intravitreal steroids. Surgical procedures and the data of ophthalmologic examination at presentation and at last follow-up were also collected. RESULTS: Included were 13 patients (20 eyes, mean age 58y). Ten patients presented after gastrointestinal or urological interventions and two presented after organ transplantation. In one patient, there was no history of previous intervention. Diagnostic vitrectomy was performed in 16 eyes (80%) and vitreous cultures were positive in 10 of the vitrectomized eyes (62.5%). In only 4 patients (31%), blood cultures were positive. All patients received systemic antifungal therapy. Sixteen eyes (80%) received intravitreal antifungal agent with voriconazole being the most commonly used. Visual acuity (VA) improved from 0.9±0.9 at initial exam to 0.5±0.8 logMAR at last follow-up (P=0.03). A trend of greater visual improvement was noted in favor of eyes treated with oral steroids (±intravitreal dexamethasone) than eyes that were not treated with steroids. The most common complication was maculopathy. Twelve eyes (60%) showed no ocular complications. CONCLUSION: High index of suspicion in patients with inciting risk factors is essential because of the low yield of blood cultures and the good general condition of patients at presentation. Visual prognosis is improved with the prompt institution of systemic and intravitreal pharmacotherapy and the immediate surgical intervention. Oral±local steroids could be considered in cases of prolonged or marked inflammatory responses in order to hasten control of inflammation and limit ocular complications.
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PURPOSE: The purpose of this study was to report our experience with intravitreal bevacizumab for inflammation-related choroidal neovascularization in two tertiary centers. METHODS: This study was a retrospective analysis of patients with choroidal neovascularization related to inflammatory diseases, treated with intravitreal bevacizumab injections (1.25 mg/0.05 mL). RESULTS: Ten eyes of 10 patients (range, 14-78 years; mean age, 44 years) with underlying uveitis were treated with intravitreal bevacizumab for inflammation-related choroidal neovascularization from 2006 to 2008. Mean follow-up time was 13 +/- 8 months, and the mean number of injections was 2.7 +/- 2. Resolved leakage on fluorescein angiography and resolution of subretinal fluid on optical coherence tomography occurred in all patients, with improvement in visual acuity in 9 of 10 eyes and no change in visual acuity in 1 of 10 eyes. Seven patients received additional treatment based on the underlying condition. Mean macular thickness on optical coherence tomography decreased from 394 +/- 116 microm to 254 +/- 52 microm (P < 0.01). Mean visual acuity improved from 0.87 +/- 0.74 logarithm of the minimum angle of resolution to 0.38 +/- 0.63 (P = 0.005). Seven patients reached a visual acuity of 0.2 logarithm of the minimum angle of resolution (Snellen 6/9) or better. CONCLUSION: Intravitreal bevacizumab is an effective treatment for choroidal neovascularization related to inflammatory diseases when inflammation is controlled.
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Inibidores da Angiogênese/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Neovascularização de Coroide/tratamento farmacológico , Uveíte/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados , Bevacizumab , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/fisiopatologia , Quimioterapia Combinada , Feminino , Angiofluoresceinografia , Glucocorticoides/administração & dosagem , Humanos , Imunossupressores/administração & dosagem , Injeções , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento , Uveíte/diagnóstico , Uveíte/fisiopatologia , Acuidade Visual/fisiologia , Corpo Vítreo , Adulto JovemRESUMO
PURPOSE: The Tyr402His variant of complement factor H (CFH) is associated with age-related macular degeneration (AMD) in several populations. Our aim was to evaluate if this single nucleotide polymorphism (SNP) is associated with AMD in the Israeli population and see if it underlies heterogeneity in clinical manifestation and responses to photodynamic therapy (PDT), which characterize neovascular AMD (NVAMD). METHODS: Genotyping for the Tyr402His variant was performed in 240 NVAMD patients (78.1+/-7 age range) and 118 controls (70.8+/-8.2 age range). Genotyping was correlated with clinical characteristics and treatment parameters in sequential 131 NVAMD patients who underwent PDT. RESULTS: TheTyr402His coding allele was associated with NVAMD in the Israeli population: odds ratio (OR)=1.9; 95% confidence interval (CI)=1.3-2.6; p=0.0002. Homozygosity for this variant was associated with an OR of 3.4 (95% CI: 1.7-6.8) for having AMD. There was no association among this SNP and age of onset of NVAMD, gender, neovascular lesion size, initial or final visual acuity, and number of PDT sessions required. CONCLUSIONS: In accordance with findings from the majority of previous study populations, the Tyr402His variant of CFH is associated with NVAMD in Israel. However, heterogeneity in clinical manifestations of NVAMD and in its response to PDT is not underlined by this CFH variant and may be accounted for by other genetic and environmental factors.
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Neovascularização de Coroide/complicações , Neovascularização de Coroide/genética , Fator H do Complemento/genética , Predisposição Genética para Doença , Degeneração Macular/complicações , Degeneração Macular/genética , Polimorfismo de Nucleotídeo Único/genética , Idoso , Feminino , Frequência do Gene , Histidina/genética , Humanos , Israel , Masculino , Fenótipo , Fotoquimioterapia , Tirosina/genéticaRESUMO
PURPOSE: Single nucleotide polymorphisms (SNPs) in the tightly linked LOC387715/ARMS2 and HTRA1 genes have been associated with age-related macular degeneration (AMD). We tested whether these SNPs are associated with AMD in Israeli populations, if they underlie variable phenotype and response to therapy in neovascular AMD (NVAMD), and if HTRA1 expression in vivo is associated with its promoter variant. METHODS: Genotyping for the rs10490924 SNP in LOC387715/ARMS2 and the rs11200638 SNP in HTRA1 was performed on 255 NVAMD patients and 119 unaffected controls from Ashkenazi and Sephardic Jewish, and from Arab origins which are the main ethnic groups composing the Israeli population. Genotyping was correlated with phenotype and response to therapy among 143 patients who underwent photodynamic therapy (PDT). HTRA1 mRNA levels in white blood cells (WBCs), measured by quantitative PCR, were correlated with genotype in 27 participants. RESULTS: Both SNPs were in almost complete linkage disequilibrium (D'=0.96-1). Homozygotes for the T allele of rs10490924 had an odds ratio (OR) of 8.6, with a 95% confidence interval (CI) of 3.5-20.8, and homozygotes for the A allele of rs11200638 had an OR of 10.7, with a 95% CI of 3.2-35.7, for having AMD (p<0.00001). There was no association among these SNPs and phenotype or response to PDT. HTRA1 mRNA levels in WBCs were not associated with rs11200638 genotypes. CONCLUSIONS: The rs10490924 SNP in LOC387715/ARMS2 and the rs11200638 SNP in HTRA1 are strongly associated with NVAMD in this Israeli population. These variants do not have a major contribution to the variable phenotype and response to PDT which characterize NVAMD.
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Povo Asiático/genética , Degeneração Macular/tratamento farmacológico , Neovascularização Patológica/genética , Fotoquimioterapia , Polimorfismo de Nucleotídeo Único/genética , Proteínas/genética , Serina Endopeptidases/genética , Idoso , Alelos , Estudos de Casos e Controles , Demografia , Feminino , Regulação da Expressão Gênica , Frequência do Gene , Genótipo , Serina Peptidase 1 de Requerimento de Alta Temperatura A , Humanos , Israel , Leucócitos/metabolismo , Degeneração Macular/genética , Masculino , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Serina Endopeptidases/sangueRESUMO
PURPOSE: To compare retinal detachment as a result of open and closed globe trauma in a pediatric age group. DESIGN: Retrospective, comparative, consecutive, interventional case series study. SETTING: Tertiary referral medical center. PATIENTS AND METHODS: One-hundred thirty-eight (5.7%) of 2,408 retinal detachments that were treated at our facility between 1980 and 2000 occurred in children aged 18 years or younger. Of these, 37 eyes (26%, n = 36) had retinal detachment following open globe injury and 23 eyes (14%, n = 20) had retinal detachment following closed globe injury. Those were compared with regard to the retinal detachment characteristics, number, types and timing of surgeries, and the anatomic and functional surgical outcome. RESULTS: Similar incidence was found in the type of retinal detachment, number of tears, extent, macular attachment type, and timing of surgery. Anatomic surgical success was achieved in 16 eyes (46%) with open globe injury and in 13 eyes (65%) with closed globe injury. The improvement in visual acuity was limited and comparable in both groups (23% to 25%), and lower than the expected according to the Ocular Trauma Score (OTS). The only predictor for favorable visual outcome of > or =20/200 was preoperative macular attachment (P =.003, Fisher exact test). CONCLUSION: The type, extent, and severity of the retinal detachment were similar in both open and closed globe injuries, suggesting that the detachment is caused by secondary indirect impact of globe deformation. The anatomic and functional surgical outcome was guarded and similar, suggesting that further surgical innovation is required to improve the visual outcome in this age group.
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Ferimentos Oculares Penetrantes/complicações , Traumatismos Oculares/complicações , Retina/lesões , Descolamento Retiniano/etiologia , Ferimentos não Penetrantes/complicações , Adolescente , Criança , Pré-Escolar , Traumatismos Oculares/cirurgia , Ferimentos Oculares Penetrantes/cirurgia , Feminino , Humanos , Incidência , Lactente , Masculino , Prognóstico , Retina/cirurgia , Descolamento Retiniano/epidemiologia , Descolamento Retiniano/cirurgia , Estudos Retrospectivos , Índices de Gravidade do Trauma , Acuidade Visual , Ferimentos não Penetrantes/cirurgiaRESUMO
This paper uses advances in the ultrafast manipulation of light to address a general need in medicine for a clinical approach that can provide a solution to a variety of disorders requiring subsurface tissue manipulation with ultralow collateral damage. Examples are age-related macular degeneration (AMD), fungal infections, tumors surrounded by overlying tissue, cataracts, etc. Although lasers have revolutionized the use of light in clinical settings, most lasers employed in medicine cannot address such problems of depth-selective tissue manipulation. This arises from the fact that they are mostly based on one photon based laser tissue interactions that provide a cone of excitation where the energy density is sufficiently high to excite heat or fluorescence in the entire cone. Thus, it is difficult to excite a specific depth of a tissue without affecting the overlying surface. However, the advent of femtosecond (fs) lasers has caused a revolution in multiphoton microscopy (Zipfel et al. Nat. Biotechnol. 2003, 21, 1369-1377; Denk et al. Science 1990, 248, 73-76) and fabrication (Kawata et al. Nature 2001, 412, 697-698). With such lasers, the photon energy density is only high enough for multiphoton processes in the focal volume, and this opens a new direction to address subsurface tissue manipulation. Here we show in an AMD animal model, Ccr2 KO knockout mutant mice, noninvasive, selective fs two-photon photobleaching of pigments associated with AMD that accumulate under and in ultraclose proximity to the overlying retina. Pathological evidence is presented that indicates the lack of collateral damage to the overlying retina or other surrounding tissue.
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Lentes de Contato , Degeneração Macular/patologia , Fotodegradação , Lesões Experimentais por Radiação/prevenção & controle , Retina/patologia , Pigmentos da Retina/metabolismo , Animais , Lasers , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia de Fluorescência por Excitação MultifotônicaRESUMO
The history of the North African Jewish community is ancient and complicated with a number of immigration waves and persecutions dramatically affecting its population size. A decade-long process in Israel of clinical-molecular screening of North African Jews with incurable autosomal recessive blindness led to the identification of a homozygous splicing mutation (c.95-2A > T; IVS2-2A > T) in RPE65, the gene encoding the isomerase that catalyzes a key step in the retinoid-visual cycle, in patients from 10 unrelated families. A total of 33 patients (four now deceased) had the severe childhood blindness known as Leber congenital amaurosis (LCA), making it the most common cause of retinal degeneration in this population. Haplotype analysis in seven of the patients revealed a shared homozygous region, indicating a population-specific founder mutation. The age of the RPE65 founder mutation was estimated to have emerged 100-230 (mean, 153) generations ago, suggesting it originated before the establishment of the Jewish community in North Africa. Individuals with this RPE65 mutation were characterized with retinal studies to determine if they were candidates for gene replacement, the recent and only therapy to date for this otherwise incurable blindness. The step from molecular anthropological studies to application of genetic medicine was then taken, and a representative of this patient subgroup was treated with subretinal rAAV2-RPE65 gene therapy. An increase in vision was present in the treated area as early as 15 days after the intervention. This process of genetically analyzing affected isolated populations as a screen for gene-based therapy suggests a new paradigm for disease diagnosis and treatment.
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Proteínas de Transporte/genética , Proteínas do Olho/genética , Amaurose Congênita de Leber/genética , Adolescente , Adulto , África do Norte/etnologia , Sequência de Bases , Criança , Pré-Escolar , Dependovirus/genética , Feminino , Terapia Genética , Vetores Genéticos , Genótipo , Humanos , Israel , Amaurose Congênita de Leber/terapia , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Estimulação Luminosa , Células Fotorreceptoras de Vertebrados/patologia , Polimorfismo de Nucleotídeo Único , Sítios de Splice de RNA , Retina/patologia , Testes Visuais , Adulto Jovem , cis-trans-IsomerasesRESUMO
Dysfunction and loss of retinal pigment epithelium (RPE) leads to degeneration of photoreceptors in age-related macular degeneration and subtypes of retinitis pigmentosa. Human embryonic stem cells (hESCs) may serve as an unlimited source of RPE cells for transplantation in these blinding conditions. Here we show the directed differentiation of hESCs toward an RPE fate under defined culture conditions. We demonstrate that nicotinamide promotes the differentiation of hESCs to neural and subsequently to RPE fate. In the presence of nicotinamide, factors from the TGF-beta superfamily, which presumably pattern RPE development during embryogenesis, further direct RPE differentiation. The hESC-derived pigmented cells exhibit the morphology, marker expression, and function of authentic RPE and rescue retinal structure and function after transplantation to an animal model of retinal degeneration caused by RPE dysfunction. These results are an important step toward the future use of hESCs to replenish RPE in blinding diseases.
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Células-Tronco Embrionárias/citologia , Células Epiteliais/citologia , Epitélio Pigmentado da Retina/citologia , Receptores de Ativinas Tipo I/farmacologia , Receptores de Activinas Tipo II/farmacologia , Ativinas/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Transplante de Células , Células-Tronco Embrionárias/efeitos dos fármacos , Células-Tronco Embrionárias/ultraestrutura , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/ultraestrutura , Fator 2 de Crescimento de Fibroblastos/farmacologia , Citometria de Fluxo , Humanos , Imunofenotipagem , Microscopia Eletrônica de Transmissão , Microscopia de Contraste de Fase , Reação em Cadeia da Polimerase , Ratos , Fator de Crescimento Transformador beta/farmacologiaRESUMO
PURPOSE: To describe the results of photodynamic therapy (PDT) using a standard protocol, developed for treating choroidal neovascularization (CNV), for the treatment of circumscribed choroidal hemangioma (CCH). METHODS: A prospective, uncontrolled, consecutive case series of patients with symptomatic CCH that were treated using the standard PDT protocol was evaluated periodically with ophthalmic exams and echography. RESULTS: Nine CCH patients were included in the study. Mean tumor height decreased from 2.7 mm before treatment to 0.8 mm at the end of the follow-up period. Mean visual acuity improved from 6/15 to 6/12. Six patients required one PDT session, two patients two sessions, and one patient three sessions. Side effects included transient visual disturbances in two patients. One patient, who concomitantly presented with age-related macular degeneration, developed CNV. CONCLUSIONS: The standard PDT protocol is effective for the treatment of CCH. Complications are uncommon. Further studies should assess the optimal PDT protocol for the treatment of CCH.
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Neoplasias da Coroide/tratamento farmacológico , Hemangioma/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Adulto , Idoso , Neoplasias da Coroide/diagnóstico por imagem , Feminino , Hemangioma/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Fotossensibilizantes/efeitos adversos , Porfirinas/efeitos adversos , Estudos Prospectivos , Resultado do Tratamento , Ultrassonografia , Verteporfina , Acuidade VisualRESUMO
Retinal and macular degenerations are a major cause of blindness. Cell transplantation is a possible therapeutic approach for the replacement of degenerating retinal cells. Here, we studied the potential of human embryonic stem cells (hESCs) to survive, integrate, and differentiate into retinal cells after intraocular transplantation. Highly enriched cultures of neural precursors (NPs) expressing transcripts of key regulatory genes of retinal development were developed from the hESCs. After spontaneous differentiation in vitro, the NPs gave rise to progeny expressing markers of retinal progenitors and photoreceptor development, though this was uncommon and cells expressing markers of mature photoreceptors were not observed. After transplantation into rat eyes, the NPs survived for 16 weeks, migrated large distances, and integrated in the host retina. Teratoma tumors were not observed. Human cells expressing rhodopsin, blue cone opsin, and neural retina leucine zipper transcription factor were observed in subretinal grafts, but not within vitreal and inner retinal grafts. The results suggest that hESCs have the potential to differentiate into retinal cells and that the subretinal microenvironment supports their differentiation toward a photoreceptor fate. This may be the first step toward further developments that eventually may allow the use of hESCs for transplantation in retinal degenerations.