RESUMEN
IMPORTANCE: Paravascular retinal abnormalities are common in highly myopic eyes. However, affected areas may be underestimated, and the pathogenesis and effects on retinal function remain unclear. OBJECTIVE: To prospectively investigate the characteristics and pathogenesis of paravascular inner retinal defects (PIRDs). DESIGN, SETTING, AND PARTICIPANTS: Prospective and observational case series (between April 2013 and April 2014) at a referral retinal practice among 28 patients (41 eyes) with PIRDs. The entire affected retinal area was examined in 4 quadrants in sequential thin sections using optical coherence tomography. The effect of PIRDs on retinal function was examined using Goldmann perimetry. MAIN OUTCOMES AND MEASURES: Morphological changes on optical coherence tomography sections and visual field test by Goldmann perimetry. RESULTS: On fundus photography, PIRDs appeared as spindle-shaped or caterpillar-shaped dark areas along the major retinal vessels disconnected from the optic disc. On optical coherence tomography cross-sections of retinal vessels, PIRDs often appeared as cystoid or fissure-like spaces; however, longitudinal optical coherence tomography sections along retinal vessels revealed that most PIRDs were actually wide defects in the inner retina or located beneath the major retinal vessels, often deviating into the vitreous cavity. Of 41 eyes with PIRDs, 37 (90%) were myopic; 21 eyes (51%) had high myopia. The mean refractive error of the eyes with PIRDs was -7.94 (95% CI, -9.48 to -6.40) diopters. The mean axial length of the eyes with PIRDs was 26.96 (95% CI, 25.42-28.49) mm. Twenty-one eyes (51%) showed epiretinal membrane in the macular area. In these eyes, PIRDs had formed along the temporal arcade vessels, which increasingly deviated toward the fovea by epiretinal membrane traction. Of 41 eyes with PIRDs, 35 showed visual field defects corresponding to the PIRD locations. The most common visual field defects were relative Bjerrum scotoma (in 75% [60 of 80]; 95% CI, 66%-85%) and nasal steps (in 59% [47 of 80]; 95% CI, 48%-70%) corresponding to the PIRD predilection locations. CONCLUSIONS AND RELEVANCE: Paravascular inner retinal defects primarily occur in eyes with high myopia or epiretinal membrane. Deviated retinal vessels due to axial elongation or epiretinal membrane traction may be involved in the pathogenesis. Paravascular inner retinal defects often cause retinal dysfunction corresponding to the location. A PIRD may partially overlap with retinal lesions previously reported as cleavage of the retinal nerve fiber layer, inner retinal cleavage, paravascular retinal cysts, or lamellar holes. However, the term PIRD more precisely describes the characteristic features of the lesion.
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Membrana Epirretinal/complicaciones , Miopía Degenerativa/complicaciones , Enfermedades de la Retina/etiología , Vasos Retinianos/patología , Adulto , Anciano , Anciano de 80 o más Años , Técnicas de Diagnóstico Oftalmológico , Membrana Epirretinal/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Miopía Degenerativa/diagnóstico , Estudios Prospectivos , Enfermedades de la Retina/diagnóstico , Escotoma/diagnóstico , Escotoma/etiología , Tomografía de Coherencia Óptica , Agudeza Visual , Pruebas del Campo Visual , Campos VisualesRESUMEN
PURPOSE: To investigate fixation behavior in eyes with advanced glaucoma using the MicroPerimeter MP-1. METHODS: We retrospectively reviewed 39 glaucoma patients who had scotomas adjacent to fixation points. Using the MP-1, we examined the stability and location of fixation with the fixation test and the microperimetry test. We examined retinal sensitivity using the central 10-2 SITA standard programs of a Humphrey Field Analyzer and the macula 10 degrees program of the MP-1 and analyzed the correlation between fixation behavior and retinal sensitivity. RESULTS: Of the 39 eyes, 37 showed "stable" fixation in the fixation test, while 30 eyes showed stable fixation in the microperimetry test. In the fixation test, 32 of 39 eyes demonstrated "predominantly central" fixation, whereas in the microperimetry test only 26 eyes exhibited the same fixation. Fixation stability correlated positively with sensitivity in the central 10 degrees diameter area (r=0.414, P=0.009). Among the six eyes showing "predominantly eccentric" fixation, the preferred retinal locus of five was in the superior or superotemporal direction from the fovea. CONCLUSIONS: The MP-1 illustrated the fixation patterns in glaucomatous eyes and the fixation patterns correlated well with retinal sensitivity.
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Fijación Ocular/fisiología , Glaucoma/fisiopatología , Retina/fisiopatología , Escotoma/fisiopatología , Pruebas del Campo Visual/métodos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Presión Intraocular , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Umbral Sensorial , Agudeza Visual/fisiología , Campos Visuales/fisiología , Percepción Visual/fisiologíaRESUMEN
PURPOSE: To evaluate retinal nerve fiber layer (RNFL) thickness and macular volume in normal eyes and in the eyes of patients with glaucoma, and to compare the usefulness of these measurements in diagnosing glaucomatous eyes. METHODS: Eighty-one eyes were divided into three groups: normal control (n = 31), early glaucoma [n = 31, mean deviation (MD) >or= -6 dB], and advanced glaucoma (n = 19, MD < -6 dB). The RNFL thickness and macular volume were measured using Stratus OCT (optical coherence tomography). Then, the diagnostic power of these parameters was evaluated. RESULTS: In eyes with early glaucoma, RNFL thickness was decreased significantly in eight of the 12 peripapillary sectors, and macular volume was decreased significantly in six of the nine macular sectors, compared with normal eyes. In the advanced glaucoma eyes, RNFL and macular volume were decreased throughout, except in RNFL thickness in the papillomacular region, and in retinal thickness in the foveal region. The area under the receiver-operating characteristic curve (AUROC) of the average RNFL (0.963) was larger than the macular volume (0.919). CONCLUSIONS: Both peripapillary RNFL thickness and macular volume were decreased even in the early stage of glaucoma. Average RNFL thickness had greater diagnostic power than macular volume.
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Glaucoma/diagnóstico , Mácula Lútea/patología , Fibras Nerviosas/patología , Células Ganglionares de la Retina/patología , Tomografía de Coherencia Óptica/métodos , Progresión de la Enfermedad , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Curva ROC , Reproducibilidad de los Resultados , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
PURPOSE: To demonstrate the visual field defects characteristic of high myopic glaucoma eyes. METHODS: Eighty-one high myopic glaucoma eyes (< or = -8 diopter(D)) and eighty moderate myopic glaucoma eyes(-3 D approximately -6 D) from patients under the age of 60 were enrolled in this study. Visual acuity, Mean Deviation (MD) of Humphrey visual field analyzer (HFA) central 30-2 program, and the pattern of central visual field defect especially at the early stage of glaucoma (MD > or = -10 dB) were compared between high and moderate myopic groups. RESULTS: HFA examination revealed significant differences in MD values between the high and moderate myopic groups (-11.8 +/- 8.9 dB and -8.4 +/- 6.9 dB, respectively, p = 0.02). Average logMAR visual acuity of the high myopic group was significantly worse than that of the moderate myopic group. The analyses of the pattern of visual field defects especially at an early glaucoma stage demonstrated that there was no specifically damaged area, such as cecocentral scotoma, in high myopic glaucoma subjects. The nasal upper area of the fixation point was the area most affected in both groups. CONCLUSIONS: High myopic glaucoma eyes demonstrated significantly lower MD and visual acuity compared to those of moderate myopic glaucoma eyes. However, at an early stage of glaucoma, no visual field defect characteristic of high myopia was observed.
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Glaucoma de Ángulo Abierto/fisiopatología , Miopía/complicaciones , Campos Visuales , Adulto , Glaucoma de Ángulo Abierto/etiología , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Agudeza VisualRESUMEN
PURPOSE: To determine whether scanning laser polarimetry with variable corneal compensation (GDx-VCC) or optical coherence tomography (OCT) is helpful for the analysis of the retinal nerve fiber layer (RNFL) thickness in glaucoma subjects with tilted disk. DESIGN: Retrospective case-control study. METHODS: We included 21 glaucomatous eyes with tilted disk and 35 glaucomatous eyes without tilted disk. Peripapillary RNFL thickness measurement by GDx-VCC and OCT, and also visual field testing with a Humphrey Field Analyzer program 30-2 (HFA) were performed in all subjects. RESULTS: In the group without tilted disk, the RNFL thickness values obtained with GDx-VCC and OCT analysis had a good correlation with mean deviation (MD), and clearly showed stage-dependent reduction. Conversely, in the group with tilted disk, a discrepancy in the RNFL measurement between GDx-VCC and OCT was observed. The correlation of RNFL measurement to the visual field was further examined at each hemifield (superior and inferior). In the group without tilted disk, the measurements of both instruments at each hemifield were in good correlation with the mean pattern deviation values. However, in the group with tilted disk, the GDx-VCC derived values did not correlate with the visual field defect in both hemifields, whereas OCT was in good association with both mean pattern deviation values. Infrared images acquired with a wavelength of nearly 780 nm revealed a high reflex from the sclera in the tilted disk. CONCLUSIONS: Our study has suggested that RNFL analysis by OCT is more suitable for the glaucoma assessment in the tilted disk compared with GDx-VCC.
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Técnicas de Diagnóstico Oftalmológico , Anomalías del Ojo/diagnóstico , Glaucoma de Ángulo Abierto/diagnóstico , Fibras Nerviosas/patología , Disco Óptico/anomalías , Células Ganglionares de la Retina/patología , Birrefringencia , Estudios de Casos y Controles , Córnea/fisiología , Femenino , Humanos , Rayos Láser , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Trastornos de la Visión/diagnóstico , Campos VisualesRESUMEN
To establish a reliable animal model of glaucoma, we examined if episcleral vein ligation in rat eyes can induce intraocular pressure (IOP) elevation and concomitant characteristic morphological features of glaucoma. IOP elevation was detected on the next day (30.1+/-4.4 mmHg: operated eyes; 21.0+/-1.8 mmHg: control eyes) and persisted at least 7 months after the procedure (24.5+/-2.3 mmHg: operated eyes; 19.7+/-1.9 mmHg: control eyes). These results suggest that episcleral vein ligation can induce very mild IOP elevation immediately after the operation, which can last over several months. Furthermore, it appears there was little variability in the patterns of IOP elevation among the individual eyes treated with episcleral vein ligation. Morphological changes were detected selectively in the retinal ganglion cell (RGC) layer and optic disc excavation was evident in the late stage of chronic IOP elevation. RGCs were selectively lost by apoptotic death. The number of RGCs was reduced by 18% at 12 weeks and eventually by 35% at 8 months postoperatively. Müller cells downregulated the expression of p27Kip1 and appeared to be partially in a reactive state even at the advanced stages of glaucoma. The expression of basic fibroblast growth factor and ciliary neurotrophic factor, which are neurotrophic factors implicated in the control of cell survivals and neuroprotection, significantly declined at the advanced stages. Taken altogether, these observations indicate that the episcleral vein ligation model based on the simple ligation procedure reproducibly provides a reliable glaucoma model and contributes to give insights into the underlying molecular and cellular bases of human glaucoma and to devise the new medication upon the disease.
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Modelos Animales de Enfermedad , Glaucoma/etiología , Esclerótica/irrigación sanguínea , Animales , Apoptosis , Femenino , Glaucoma/metabolismo , Glaucoma/patología , Presión Intraocular , Ligadura , Factores de Crecimiento Nervioso/metabolismo , Ratas , Ratas Wistar , Retina/metabolismo , Células Ganglionares de la Retina/patología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , VenasRESUMEN
We investigated if bone marrow stromal cells (BMSCs) transplanted into the vitreous body of a glaucoma model eye could be integrated in the host retina and also whether they could rescue the retinal ganglion cells (RGCs) from death induced by the elevated intraocular pressure. Glaucoma was induced in the right eye of adult Wistar rats by ligating the episcleral veins. The GFP-expressing BMSCs (GFP-BMSCs) were injected into the vitreous body of both the control and the glaucomatous eyes. After transplantation, GFP-BMSCs were mostly present along with the inner limiting membrane and only a few cells were integrated into the ganglion cell layer. At 2 or 4 weeks after transplantation, GFP-BMSCs were observed to express various trophic factors. The BMSCs injected glaucoma model eyes showed less reduction in the number of RGCs compared to the glaucomatous eyes with PBS injection. This study suggests that BMSC transplantation may be worthy as a neuroprotective tool to treat glaucoma.
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Células de la Médula Ósea/citología , Trasplante de Médula Ósea , Glaucoma/terapia , Animales , Modelos Animales de Enfermedad , Factores de Crecimiento de Fibroblastos/genética , Factores de Crecimiento de Fibroblastos/metabolismo , Proteínas Fluorescentes Verdes/análisis , Factor de Crecimiento de Hepatocito/genética , Factor de Crecimiento de Hepatocito/metabolismo , Factores de Crecimiento Nervioso/genética , Factores de Crecimiento Nervioso/metabolismo , Ratas , Ratas Wistar , Retina/química , Retina/citología , Retina/metabolismo , Células del Estroma/trasplanteRESUMEN
PURPOSE: To determine the indications for internal limiting membrane (ILM) removal in stage 3 idiopathic macular holes (MHs). METHODS: Focal posterior vitreous detachments (PVDs) at MH rims were examined preoperatively by optical coherence tomography and binocular slit-lamp fundus examination in 19 patients retrospectively. All eyes underwent pars plana vitrectomy and creation of a PVD, and some eyes underwent a second surgery to remove the ILM. Indications of ILM removal for MH closure were discussed. RESULTS: Preoperatively, 9 eyes did not (non-PVD group) and 10 eyes did (PVD group) have complete focal PVDs. In all nine eyes in the non-PVD group, MHs were closed after the creation of a PVD without ILM peeling (P <0.05, chi test). In the PVD group, 5 eyes (50%) had MHs closed by making PVD complete without ILM removal, and 5 eyes (50%) required ILM removal in a second surgery. In the end, closure of MHs was achieved in all eyes. CONCLUSION: Anatomic closure of stage 3 idiopathic MHs without a PVD at the rim of the hole may be achieved only by creating a PVD without ILM removal.
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Membrana Epirretinal/cirugía , Perforaciones de la Retina/cirugía , Adulto , Anciano , Membrana Basal/cirugía , Técnicas de Diagnóstico Oftalmológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Perforaciones de la Retina/clasificación , Perforaciones de la Retina/diagnóstico , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Agudeza Visual , Vitrectomía , Cuerpo Vítreo/cirugíaRESUMEN
Tlx belongs to a class of orphan nuclear receptors that underlies many aspects of neural development in the CNS. However, the fundamental roles played by Tlx in the control of eye developmental programs remain elusive. By using Tlx knock-out (KO) mice, we show here that Tlx is expressed by retinal progenitor cells in the neuroblastic layer during the period of retinal layer formation, and it is critical for controlling the generation of appropriate numbers of retinal progenies through the activities of cell cycle-related molecules, cyclin D1 and p27Kip1. Tlx expression is restricted to Müller cells in the mature retina and appears to control their proper development. Furthermore, we show that Tlx is expressed by immature astrocytes that migrate from the optic nerve onto the inner surface of the retina and is required for their generation and maturation, as assessed by honeycomb network formation and expression of R-cadherin, a critical component for vasculogenesis. The impaired astrocyte network formation on the inner retinal surface is accompanied by the loss of vasculogenesis in Tlx KO retinas. Our studies thus indicate that Tlx underlies a fundamental developmental program of retinal organization and controls the generation of the proper numbers of retinal progenies and development of glial cells during the protracted period of retinogenesis.
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Astrocitos/citología , Proteínas del Ojo/fisiología , Neuroglía/citología , Receptores Citoplasmáticos y Nucleares/fisiología , Retina/citología , Animales , Apoptosis , Astrocitos/metabolismo , Cadherinas/biosíntesis , Cadherinas/genética , Recuento de Células , Ciclo Celular , Proteínas de Ciclo Celular/fisiología , Diferenciación Celular , Movimiento Celular , Ciclina D1/fisiología , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Anomalías del Ojo/genética , Proteínas del Ojo/biosíntesis , Proteínas del Ojo/genética , Regulación del Desarrollo de la Expresión Génica , Ratones , Ratones Noqueados , Neovascularización Fisiológica/genética , Neuroglía/metabolismo , Receptores Citoplasmáticos y Nucleares/biosíntesis , Receptores Citoplasmáticos y Nucleares/deficiencia , Receptores Citoplasmáticos y Nucleares/genética , Retina/embriología , Retina/crecimiento & desarrollo , Vasos Retinianos/embriología , Vasos Retinianos/crecimiento & desarrollo , Proteínas Supresoras de Tumor/fisiologíaRESUMEN
OBJECTIVE: To examine the results of pars plana vitrectomy for nonclearing vitreous opacities associated with ocular sarcoidosis that is resistant to corticosteroid treatment. METHODS: Eight consecutive patients (11 eyes) with vitreous opacities and uveitis associated with sarcoidosis were studied. All patients were resistant to or intolerant of corticosteroid therapy. All eyes underwent pars plana vitrectomy, followed by evaluation of visual acuity and recording of the grade of inflammation and complications. RESULTS: Seven eyes had gained two or more lines of Snellen visual acuity six months postoperatively; visual acuity remained unchanged in the other four eyes. Vitreous inflammation was reduced in all cases. Severe postoperative inflammation did not recur in any eyes. Five eyes developed visually significant cataracts and underwent cataract extraction and intraocular lens insertion within 8-30 months. Based on slit-lamp biomicroscopy and fluorescein angiography, preoperative cystoid macular edema in five eyes resolved or improved within six months after vitrectomy. Postoperative complications included elevated intraocular pressure in three eyes, cataract formation in six eyes, epiretinal membrane formation in one eye, and choroidal neovascularization in one eye. None of the patients developed cystoid macular edema postoperatively. Only three patients received systemic corticosteroids after surgery. At the final visit, only one patient required systemic corticosteroid therapy. CONCLUSIONS: Pars plana vitrectomy appears to have beneficial effects on restoring vision, stabilizing vitreous inflammation, and reducing systemic corticosteroid requirements in eyes with thick vitreous opacities associated with sarcoidosis that is resistant to medical treatment.
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Oftalmopatías/cirugía , Sarcoidosis/cirugía , Uveítis/cirugía , Vitrectomía , Cuerpo Vítreo/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Resistencia a Medicamentos , Oftalmopatías/etiología , Femenino , Glucocorticoides/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Sarcoidosis/complicaciones , Sarcoidosis/tratamiento farmacológico , Uveítis/complicaciones , Uveítis/tratamiento farmacológico , Agudeza Visual , Cuerpo Vítreo/patologíaRESUMEN
PURPOSE: To examine retrospectively the visual outcomes in patients undergoing vitrectomy for epiretinal membranes secondary to sarcoid uveitis. METHODS: Eleven consecutive patients (11 eyes) with epiretinal membrane and uveitis associated with sarcoidosis underwent pars plana vitrectomy. RESULTS: Nine eyes (82%) gained two or more lines of Snellen visual acuity at 1-12 months after surgery. However, 4 of these 9 eyes lost two or more lines of Snellen visual acuity by the final visit. Overall, 5 eyes (45%) had attained at least two Snellen lines of visual acuity improvement, 5 eyes (45%) were unchanged, and 1 eye (10%) had worsened by two lines at the final visit. Nine eyes (81%) achieved visual acuity of 20/40 or better by the final visit. Slit-lamp biomicroscopy and fluorescein angiography showed that cystoid macular edema had resolved in 4 of 7 eyes postoperatively; vitritis improved in all cases. Postoperative complications included cataract formation, glaucoma, and membrane recurrence. Subsequent surgeries consisted of cataract extraction in 2 eyes and membrane peeling in 1 eye. CONCLUSIONS: Pars plana vitrectomy appears to have a beneficial effect on restoring vision in eyes with epiretinal membrane and uveitis associated with sarcoidosis, but final visual acuity was limited by the development of cataract and membrane recurrence.
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Membrana Epirretinal/etiología , Membrana Epirretinal/cirugía , Sarcoidosis/complicaciones , Uveítis/complicaciones , Uveítis/etiología , Anciano , Membrana Epirretinal/fisiopatología , Femenino , Humanos , Edema Macular/etiología , Edema Macular/fisiopatología , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Agudeza Visual , VitrectomíaRESUMEN
PURPOSE: To examine the ultrastructure of the rd retina after transplantation of small micro-aggregates of neural retina in order to determine their survival and integration with the host retina and for sites of communication between transplant and host neurons. METHODS: Neonatal micro-aggregates from transgenic mice expressing a LacZ gene reporter gene in their rods were transplanted into the subretinal space of transgenic rd mice expressing a LacZ reporter gene in their rod bipolar cells. The mice were killed at various times after transplantation surgery and studied by light and electron microscopy. RESULTS: Retinal transplants survived well, as long as 8 months, without signs of rejection and were well integrated into the host retina. Cell bodies of transplanted rods made membrane-to-membrane contacts with rod bipolar cells of the host at areas where there were gaps in the host external plexiform layer. One synaptic process of a transplanted rod was found on the vitreal side of the host's external limiting membrane. In two cases, a postsynaptic process in a transplanted rod spherule contained an Xgal label, implying that it belonged to a host rod bipolar. There was evidence of extension of processes between host and transplant retinas involving astrocytic rather than neural structures. CONCLUSIONS: Retinal allografts to the subretinal space of rd mice survive indefinitely. Close but non-synaptic contacts occur between transplant and host neurons that could allow ephaptic communication between these two retinas. Evidence of synaptic contacts between transplant and host was difficult to find.
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Retina/trasplante , Degeneración Retiniana/cirugía , Animales , Animales Recién Nacidos , Membrana Celular/ultraestructura , Supervivencia Celular , Trasplante de Células , Interneuronas/ultraestructura , Ratones , Ratones Transgénicos , Retina/ultraestructura , Degeneración Retiniana/genética , Degeneración Retiniana/patología , Trasplante HomólogoRESUMEN
PURPOSE: To examine the ultrastructure of the adult rd mouse retina in order to determine what structures are altered or lost and thus to better interpret changes produced by photoreceptor and/or retinal transplantation in this model of retinal degeneration. METHODS: rd mutant mice expressing a LacZ reporter gene in rod bipolars were used in order to identify these cells and their processes. Mice of age 6 weeks to 5 months were studied by electron microscopy, concentrating on the posterior pole where retinal transplants are usually placed. RESULTS: The adult rd mouse retina contains degenerating cones, cone outer segments, cone synaptic pedicles with synaptic vesicles and post-synaptic contacts. The major abnormalities occur in the subretinal space where all traces of rods are gone and the main structures are inner segments of cones. These inner segments are smaller than normal, contain fewer and smaller mitochondria, have organized arrays of microtubules, resembling those in cone axonal processes, and are completely engulfed by massive proliferation of apical processes of the retinal epithelium. The subretinal space is well defined by the external limiting membrane vitreally and the retinal epithelium choroidally. Muller cells extend globular rather than filamentous processes into the subretinal space which contact the apical processes of the epithelium. Rod bipolar cells survive and retain processes in the external plexiform layer. CONCLUSIONS: The adult rd mouse retains structural elements necessary for phototransduction and transmission of signals to the inner layers of the retina by the cone system. The major deficits are located in the subretinal space where all rods are lost and cone inner segments undergo a slow degeneration. Rod bipolar cells survive but appear to be de-afferented; there was no evidence that they contact residual cone processes in the external plexiform layer. The rd mouse is a logical model to study the effects of transplantation of photoreceptors because second- and third-order retinal neurons as well as degenerating cones survive in the adult retina.