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AIMS/INTRODUCTION: To conduct a multicenter survey of visually impaired patients with diabetes mellitus (DM) and to identify the physical and ocular characteristics that lead to blindness in Japan. MATERIALS AND METHODS: Visually impaired patients with diabetes mellitus in Japan were divided into blind and low-vision groups according to the World Health Organization classification. Data on parameters related to diabetes mellitus and ocular complications in the right and left eyes were collected from 19 highly advanced medical facilities and compared between the two groups. RESULTS: Among 408 visually impaired persons (blind group: 257, low-vision group: 151), 72.1% were under 70 years of age. The rates of neovascular glaucoma (NVG) (right eye, P = 0.041; left eye, P = 0.0031) or proliferative diabetic retinopathy (PDR) (right eye: P = 0.014, left eye: P = 0.0047) and the rate of proliferative membrane beyond half of the retinal area (right eye: P = 0.0263, left eye: P = 0.037) were significantly higher in the blind group. The direct cause of visual impairment was retinal atrophy, common in both groups. Neovascular glaucoma and diabetic macular edema were equally prevalent in the blind and low-vision groups, respectively. CONCLUSIONS: In Japan, blind patients with diabetes mellitus are characterized by severe conditions such as neovascular glaucoma and progressive proliferative diabetic retinopathy upon their initial visit to an advanced care facility. These results highlight the importance of monitoring retinopathy through regular ophthalmological examinations, internal medicine, and appropriate therapeutic intervention.
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Ceguera , Retinopatía Diabética , Personas con Daño Visual , Humanos , Japón/epidemiología , Masculino , Femenino , Anciano , Persona de Mediana Edad , Retinopatía Diabética/epidemiología , Retinopatía Diabética/etiología , Ceguera/etiología , Ceguera/epidemiología , Personas con Daño Visual/estadística & datos numéricos , Baja Visión/etiología , Baja Visión/epidemiología , Adulto , Anciano de 80 o más Años , Diabetes Mellitus/epidemiologíaRESUMEN
INTRODUCTION: We compared postoperative metamorphopsia and optical coherence tomography (OCT) findings between eyes that underwent internal limiting membrane (ILM) peeling and the inverted flap (IF) technique for macular hole (MH). METHODS: This retrospective analysis included 64 eyes of 64 patients with idiopathic MH whose MH was closed after initial surgery. Thirty-nine patients were treated with pars plana vitrectomy (PPV) with ILM peeling, and 25 patients were treated with PPV with the IF technique. Best corrected visual acuity (BCVA), severity of metamorphopsia, and OCT images were collected before and 3, 6, and 12 months postoperatively. Based on the OCT images, the status of the external limiting membrane (ELM) and ellipsoid zone and the presence of hyperreflective plugs were assessed. RESULTS: At baseline and 3, 6, and 12 months postoperatively, BCVA and severity of metamorphopsia were not significantly different between groups. The status of the ELM was significantly worse in the IF group than in the ILM peeling group at 3 and 6 months postoperatively. Significantly more hyperreflective plugs were observed in the IF group than in the ILM peeling group at 3 and 6 months postoperatively. Stepwise multiregression analysis revealed that hyperreflective plugs were significantly associated with the severity of metamorphopsia at 12 months postoperatively. DISCUSSION/CONCLUSION: The alterations on the OCT were fewer in the ILM peeling group than in the IF group, while no significant differences were observed in postoperative severity of metamorphopsia between groups. Metamorphopsia was worse in eyes with hyperreflective plugs.
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Membrana Basal , Perforaciones de la Retina , Colgajos Quirúrgicos , Tomografía de Coherencia Óptica , Trastornos de la Visión , Agudeza Visual , Vitrectomía , Humanos , Tomografía de Coherencia Óptica/métodos , Perforaciones de la Retina/cirugía , Perforaciones de la Retina/diagnóstico , Estudios Retrospectivos , Femenino , Masculino , Vitrectomía/métodos , Membrana Basal/cirugía , Anciano , Trastornos de la Visión/diagnóstico , Trastornos de la Visión/fisiopatología , Trastornos de la Visión/etiología , Estudios de Seguimiento , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Membrana Epirretinal/cirugía , Membrana Epirretinal/diagnósticoRESUMEN
PURPOSE: To compare stereopsis and foveal microstructure after internal limiting membrane peeling and inverted internal limiting membrane flap technique in patients with macular hole. DESIGN: Retrospective observational study. METHODS: Sixty-six patients with macular hole were included, of whom 41 underwent 25-gauge pars-plana vitrectomy with complete internal limiting membrane peeling (Peeling group) and 25 with the inverted flap technique (Inverted group). We evaluated stereopsis using the Titmus Stereo Test and the TNO stereo test, best-corrected visual acuity, macular hole closure rate, and foveal microstructure with optical coherence tomography before and at 3, 6, and 12 months after surgery. MAIN OUTCOME MEASURES: Stereopsis and foveal microstructure. RESULTS: Preoperatively, no difference was observed in the base and minimum diameters of macular hole, Titmus Stereo Test score, TNO stereo test score, and best-corrected visual acuity between the Peeling and Inverted groups. The macular hole closure rate in the Peeling and Inverted groups were 97.6% and 100%, respectively, with no significant difference between groups. At 12 months postoperatively, Titmus Stereo Test score (2.1 ± 0.4 in the peeling and 2.2 ± 0.4 in the inverted groups), TNO stereo test score (2.3 ± 0.4 and 2.2± 0.5), and best-corrected visual acuity (0.20 ± 0.18 and 0.24 ± 0.25) were not significantly different between groups (p = 0.596, 0.332, respectively). The defect of the external limiting membrane was more common in the Inverted group than in the Peeling group at 6 months after surgery (5.4 vs. 28.0%; p < 0.05). No statistically significant inter-group differences were noted in the ellipsoid zone defect ratio throughout the follow-up period. CONCLUSIONS: There was no difference in postoperative stereopsis nor foveal microstructure between the internal limiting membrane peeling group and the inverted group in patients with macular hole.
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Membrana Epirretinal , Perforaciones de la Retina , Humanos , Perforaciones de la Retina/cirugía , Membrana Epirretinal/cirugía , Membrana Basal/cirugía , Agudeza Visual , Fóvea Central/diagnóstico por imagen , Vitrectomía/métodos , Estudios Retrospectivos , Tomografía de Coherencia ÓpticaRESUMEN
PURPOSE: To investigate the 5-year treatment outcomes of retinopathy of prematurity in infants <500 g birth weight and compare laser and anti-vascular endothelial growth factor therapies. METHODS: A multicenter retrospective study comprised 24 eyes of 13 patients treated for Type 1 retinopathy of prematurity, followed for 5 years. Initial treatment was laser and anti-vascular endothelial growth factor in 13 and 11 eyes, respectively. Data collected included sex, birth characteristics, retinopathy of prematurity characteristics at the time of treatment, best-corrected visual acuity (BCVA), spherical equivalent, and astigmatism at 5 years posttreatment. RESULTS: Median BCVA was 0.15 logarithm of the minimum angle of resolution (interquartile range, 0.0-0.5). Snellen BCVA was ≥20/40 in 73% and ≥20/20 in 27% of eyes. Median spherical equivalent was -2.37 (interquartile range, -6.1 to -0.1); 75% had myopia (≤-0.5 D), and 25% had high myopia (≤-6.0 D). Median astigmatism was 1.25 (interquartile range, 0.9-3.0); 46% had ≥1.5 D. Anti-vascular endothelial growth factor-treated eyes showed less myopia ( P < 0.009), with no BCVA or astigmatism difference ( P = 0.997, P = 0.271) compared with laser-treated eyes. CONCLUSION: One-quarter of the eyes exhibited good visual acuity (Snellen BCVA of ≥20/20) 5 years after retinopathy of prematurity treatment. Refractive errors were common. Anti-vascular endothelial growth factor therapy may be superior to laser therapy in myopic refractive error.
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Astigmatismo , Miopía , Errores de Refracción , Retinopatía de la Prematuridad , Recién Nacido , Lactante , Humanos , Astigmatismo/terapia , Retinopatía de la Prematuridad/cirugía , Estudios Retrospectivos , Factores de Crecimiento Endotelial , Resultado del Tratamiento , Coagulación con LáserRESUMEN
OBJECTIVES: To compare real-world, long-term outcomes of laser and anti-vascular endothelial growth factor (VEGF) therapies in patients with retinopathy of prematurity (ROP). METHODS: This was a multicentre retrospective study. We included 264 eyes of 139 patients treated for type 1 ROP or aggressive ROP (AROP) who were followed for at least 4 years. Laser treatment was initially performed in 187 eyes (the laser group), and anti-VEGF therapy was initially performed in 77 eyes (the anti-VEGF group). We collected data on sex, birth characteristics, zone, stage, and the presence of plus disease at the time of treatment and best-corrected visual acuity (BCVA), spherical equivalent (SE), and ocular complications (amblyopia and strabismus) in patients aged 4-6 years. We investigated the associations between treatment outcomes (BCVA, SE and the presence of amblyopia and strabismus) and influencing factors, including treatment procedure (anti-VEGF or laser therapy), sex, birth characteristics, zone, stage, and the presence of plus disease, using multivariable analysis and logistic regression analyses. RESULTS: The initial treatment procedure was not associated with any specific treatment outcome. Subgroup analysis of patients with zone I ROP revealed that the anti-VEGF-treated eyes had significantly better BCVA and higher SE than laser-treated eyes (p = 0.004, p = 0.009, respectively). Female patients presented significantly better BCVA, less amblyopia and less strabismus than male patients (p < 0.001, p = 0.029, p = 0.008, respectively). CONCLUSIONS: In zone I ROP, anti-VEGF therapy led to better visual acuity and less myopic refractive error than laser treatment.
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Ambliopía , Retinopatía de la Prematuridad , Estrabismo , Recién Nacido , Humanos , Masculino , Femenino , Inhibidores de la Angiogénesis , Retinopatía de la Prematuridad/tratamiento farmacológico , Retinopatía de la Prematuridad/cirugía , Factor A de Crecimiento Endotelial Vascular/uso terapéutico , Ambliopía/tratamiento farmacológico , Estudios Retrospectivos , Coagulación con Láser/métodos , Resultado del Tratamiento , Inyecciones Intravítreas , Rayos Láser , Edad GestacionalRESUMEN
PURPOSE: To investigate age-specific prevalence of disease subtypes and baseline best-corrected visual acuity (BCVA) in Japanese patients with treatment-naïve neovascular age-related macular degeneration (nAMD). STUDY DESIGN: Retrospective multicenter case series. METHODS: We reviewed the records of patients with treatment-naïve nAMD who underwent initial treatment in 14 institutions in Japan sometime during the period from 2006 to 2015. In patients in whom both eyes were treated, only the eye treated first was included for analysis. The patients were stratified by age for the analysis. RESULTS: In total, 3096 eyes were included. The overall prevalence of subtypes was as follows: typical AMD, 52.6%; polypoidal choroidal vasculopathy (PCV), 42.8%; retinal angiomatous proliferation (RAP), 4.6%. The number of eyes in each age group was as follows: younger than 60 years, 199; 60s, 747; 70s, 1308; 80s, 784; 90 years or older, 58. The prevalence of typical AMD in each age group was 51.8%, 48.1%, 52.1%, 57.7%, and 55.2%, respectively. The prevalence of PCV was 46.7%, 49.1%, 44.7%, 34.4%, and 19.0%, respectively. The prevalence of RAP was 1.5%, 2.8%, 3.2%, 7.9%, and 25.9%, respectively. The prevalence of PCV decreased with age, whilst that of RAP increased. The prevalence of RAP was higher than that of PCV in patients aged 90 years or older. The mean baseline BCVA (logMAR) was 0.53. In each age group, the mean baseline BCVA was 0.35, 0.45, 0.54, 0.62, and 0.88, respectively. The mean logMAR BCVA at baseline significantly worsened with age (P < 0.001). CONCLUSION: The prevalence of nAMD subtypes differed according to age in Japanese patients. The baseline BCVA worsened with age.
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Degeneración Macular , Degeneración Macular Húmeda , Humanos , Pueblos del Este de Asia , Angiografía con Fluoresceína , Estudios de Seguimiento , Inyecciones Intravítreas , Degeneración Macular/diagnóstico , Degeneración Macular/epidemiología , Degeneración Macular/tratamiento farmacológico , Prevalencia , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Agudeza Visual , Degeneración Macular Húmeda/diagnóstico , Degeneración Macular Húmeda/epidemiología , Persona de Mediana Edad , Anciano , Anciano de 80 o más AñosRESUMEN
Even after successful surgery, the stereopsis of retinal detachment (RD) patients is inferior to that of normal subjects. However, it is unclear which visual dysfunction in the affected eye is responsible for the postoperative stereopsis impairment. This study included 127 patients after successful surgery for unilateral RD. Stereopsis, best-corrected visual acuity (BCVA), severity of metamorphopsia, letter contrast sensitivity and amount of aniseikonia were examined at 6-month postoperatively. Stereopsis was assessed using the Titmus Stereo Test (TST) and TNO stereotest (TNO). Postoperative stereopsis (log) in patients with RD were 2.09 ± 0.46 in the TST and 2.56 ± 0.62 in the TNO. Multivariate analysis with stepwise regression revealed postoperative TST was associated with BCVA, and TNO was associated with BCVA, letter contrast sensitivity, metamorphopsia and absolute values of aniseikonia. In a subgroup analysis that selected those with more impaired stereopsis, postoperative TST was associated with BCVA (p < 0.001), and TNO was associated with letter contrast sensitivity (p < 0.005) and absolute values of aniseikonia (p < 0.05) by multivariate analysis. Deterioration of stereopsis after RD surgery was affected by a variety of visual dysfunctions. The TST was affected by visual acuity, while the TNO was affected by contrast sensitivity and aniseikonia.
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PURPOSE: To evaluate the vision-related quality of life (VR-QOL) before and after intravitreal ranibizumab injections (IVR) for central retinal vein occlusion (CRVO) and to investigate subscale items of VR-QOL in detail. STUDY DESIGN: A multicenter, open-label, prospective and comparative study. METHODS: Twenty-three patients with treatment naïve CRVO and 22 age-matched normal controls were included. VR-QOL was assessed by 25-Item Visual Function Questionnaire (VFQ-25) before and up to 12 months post-treatment. The VFQ-25 composite score and 12 subscales were compared between CRVO patients and normal controls. RESULTS: The VFQ-25 composite scores of CRVO patients showed significant improvement throughout the treatment period compared with baseline. The VFQ-25 composite scores both before and after treatment for CRVO were significantly lower than in normal controls. The subscale items, including general health, general vision, near activities, social functioning, mental health, role difficulties, dependency, and peripheral vision in CRVO, were significantly lower than in the normal controls even after treatment. CONCLUSION: Vision-related QOL was low in patients with CRVO before treatment and improved with IVR. In spite of the improvements, several subscale items remained lower than in normal controls following treatment. Attention should be paid to the patients with CRVO and their decreased visual, social and psychological QOL.
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Ranibizumab , Oclusión de la Vena Retiniana , Humanos , Ranibizumab/uso terapéutico , Calidad de Vida , Oclusión de la Vena Retiniana/diagnóstico , Oclusión de la Vena Retiniana/tratamiento farmacológico , Estudios Prospectivos , Agudeza Visual , Inyecciones Intravítreas , Inhibidores de la Angiogénesis/uso terapéuticoRESUMEN
SYNOPSIS/PRECIS: We investigated the relationship between contrast sensitivity (CS) and vision-related quality of life (VR-QOL) in patients with central retinal vein occlusion following ranibizumab intravitreal injection; CS showed a stronger association with VR-QOL than visual acuity. BACKGROUND/AIMS: To investigate the relationship between CS, VR-QOL and optical coherence tomography (OCT) findings in patients with cystoid macular oedema secondary to central retinal vein occlusion (CRVO-CMO) following intravitreal injection of ranibizumab. METHODS: This was a multicentre, open-label, single-arm, prospective study. The study included 23 patients with CRVO-CMO who were followed up for 12 months after treatment. The best-corrected visual acuity (BCVA), letter contrast sensitivity (LCS) and OCT images were obtained every month. For VR-QOL assessment, the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) was administered to the patients before treatment and at 3, 6 and 12 months following treatment. RESULTS: The LCS and VFQ-25 composite score improved significantly from baseline to 12 months following treatment. The multiple regression analysis revealed that the LCS of the affected eye and BCVA of the fellow eye were related to the VFQ-25 composite score following treatment. The LCS improvement showed a significant correlation with the improvement in the VFQ-25 composite score, whereas the BCVA improvement was not correlated with the improvement in the VFQ-25 composite score. Stepwise multiple regression analyses revealed that, at the time of macular oedema resolution, the distance between the external limiting membrane and retinal pigment epithelium (ELM-RPE) and average ganglion cell-inner plexiform layer (GCIPL) thickness were associated with LCS. CONCLUSION: CS had a stronger association with VR-QOL than with BCVA in patients with CRVO-CMO. With the resolution of macular oedema, CS was associated with ELM-RPE thickness and average GCIPL thickness.
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Edema Macular , Oclusión de la Vena Retiniana , Humanos , Sensibilidad de Contraste , Inyecciones Intravítreas , Edema Macular/diagnóstico , Edema Macular/tratamiento farmacológico , Edema Macular/etiología , Estudios Prospectivos , Calidad de Vida , Ranibizumab/uso terapéutico , Oclusión de la Vena Retiniana/complicaciones , Oclusión de la Vena Retiniana/diagnóstico , Oclusión de la Vena Retiniana/tratamiento farmacológico , Tomografía de Coherencia ÓpticaRESUMEN
Anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) improves visual acuity. However, repeated injections during routine outpatient visits are required to maintain this effect. The recent sudden global outbreak of coronavirus disease 2019 (COVID-19) had a major impact on daily life, including medical care, such as the provision of VEGF therapy. We retrospectively investigated the relationship between the number of anti-VEGF injections for DME and the number of new COVID-19-positive patients at 23 centers in Japan. We also surveyed ophthalmologists regarding the impact of the COVID-19 pandemic on anti-VEGF therapy. In the third and fourth waves of the pandemic, when the number of infected patients increased, the number of injections significantly decreased. In the first, third, and fourth waves, the number of injections increased significantly during the last month of each wave. Approximately 60.9% of ophthalmologists reported that the number of injections decreased after the pandemic. Of the facilities, 52.2% extended the clinic visit intervals; however, there was no significant difference in the actual number of injections given between before and after the pandemic. Although the number of injections temporarily decreased, Japanese ophthalmologists maintained the total annual number of anti-VEGF injections for DME during the pandemic.
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The aim of the present study was to investigate changes in metamorphopsia in patients with diabetic macular edema (DME) following intravitreal aflibercept injection (IVA) with the treat and extend (TAE) regimen for a year. We performed a post hoc analysis of a multicenter, open-label, single-arm, prospective study. The study included 20 patients with DME. All eyes received 3 monthly loading injections of 2 mg aflibercept, followed by a TAE regimen. Every visit, the severity of metamorphopsia and the best-corrected visual acuity (BCVA) were evaluated, and optical coherence tomography (OCT) images were obtained. The severity of metamorphopsia was measured using M-CHARTS. The metamorphopsia scores before treatment and at 1, 2, 3, 6 and 12 months following treatment were 0.25 ± 0.23, 0.21 ± 0.15, 0.19 ± 0.23, 0.14 ± 0.16, 0.17 ± 0.20 and 0.10 ± 0.17, respectively, with significant improvement from before treatment to 3 and 12 months following treatment (p < 0.05 and p < 0.005, respectively). At the time of macular edema resolution, the presence of an epiretinal membrane (ERM) was associated with the metamorphopsia score (p < 0.05). In conclusion, the metamorphopsia score in patients with DME improved following IVA with the TAE regimen for one year. The presence of ERM was associated with the metamorphopsia score.
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Diabetes Mellitus , Retinopatía Diabética , Membrana Epirretinal , Edema Macular , Receptores de Factores de Crecimiento Endotelial Vascular , Humanos , Inhibidores de la Angiogénesis/efectos adversos , Diabetes Mellitus/tratamiento farmacológico , Retinopatía Diabética/complicaciones , Retinopatía Diabética/tratamiento farmacológico , Membrana Epirretinal/complicaciones , Inyecciones Intravítreas , Edema Macular/complicaciones , Estudios Prospectivos , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/efectos adversos , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Trastornos de la Visión , Agudeza VisualRESUMEN
Tissue-specific stem cells exist in tissues and organs, such as skin and bone marrow. However, their pluripotency is limited compared to embryonic stem cells. Culturing primary cells on plastic tissue culture dishes can result in the loss of multipotency, because of the inability of tissue-specific stem cells to survive in feeder-less dishes. Recent findings suggest that culturing primary cells in medium containing feeder cells, particularly genetically modified feeder cells expressing growth factors, may be beneficial for their survival and proliferation. Therefore, the aim of this study was to elucidate the role of genetically modified human feeder cells expressing growth factors in maintaining the integrity of primary cultured human deciduous dental pulp cells. Feeder cells expressing leukemia inhibitory factor, bone morphogenetic protein 4, and basic fibroblast growth factor were successfully engineered, as evidenced by PCR. Co-culturing with mitomycin-C-treated feeder cells enhanced the proliferation of newly isolated human deciduous dental pulp cells, promoted their differentiation into adipocytes and neurons, and maintained their stemness properties. Our findings suggest that genetically modified human feeder cells may be used to maintain the integrity of primary cultured human deciduous dental pulp cells.
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PURPOSE: To evaluate the clinical characteristics, treatment trends, and visual prognosis of submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD) and retinal arterial macroaneurysm (RAM). METHODS: This retrospective study enrolled 187 Japanese patients with SMH at 10 institutions from 2015 to 2018. Medical records including SMH etiology, best-corrected visual acuity (BCVA), fundus photographs, optical coherence tomography images, and selected treatments were analyzed. RESULTS: Major causes of SMH were typical nAMD (tnAMD) (18%), polypoidal choroidal vasculopathy (PCV) (50%) and RAM (29%). Age, male/female ratio, baseline BCVA, central retinal thickness, and involved retinal layers were significantly different between etiologies (all P<0.0001). Treatment with anti-vascular endothelial growth factor drugs with and without intravitreal gas injection was chosen for half of eyes in the tnAMD and PCV groups, whereas vitrectomy was performed in 83.7% of eyes with RAM. The final BCVA improved significantly from baseline in the PCV and RAM groups (P = 0.0009, P<0.0001) and final BCVA was significantly better in the PCV group at a level similar to the other groups (P = 0.0007, P = 0.0008). BCVA improvement from baseline was significantly greater in the RAM group compared with the tnAMD (P = 0.0152) and PCV (P = 0.017) groups. Multivariate analysis revealed better final BCVA was significantly associated with younger age (P = 0.0054), better baseline BCVA (P = 0.0021), RAM subtype (P = 0.0446), and no tnAMD (P = 0.001). CONCLUSIONS: The characteristics of, and treatment strategy for, SMH were different between the underlying diseases. Anti-vascular endothelial growth factor treatment with or without expansile gas was mainly chosen for SMH in tnAMD and PCV, whereas vitrectomy with gas was the most common treatment for RAM, and the higher rate for vitrectomy might result in the greater BCVA improvement in the RAM group than in the other groups. Final BCVA was better in PCV, RAM, and tnAMD, in that order, because patients with PCV were younger and had better baseline BCVA.
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Degeneración Macular , Macroaneurisma Arterial de Retina , Enfermedades Vasculares , Factores de Crecimiento Endotelial , Femenino , Hemorragia , Humanos , Japón , Degeneración Macular/complicaciones , Masculino , Retina , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Multiple intravitreal injections, which are painful and costly, are often required in the treatment of retinal disorders. Therefore, a novel drug delivery system using hydrogels is currently being evaluated as an alternative. This study aimed to evaluate the ability of tetra-armed polyethylene glycol (tetra-PEG) gel for sustained release in vitro. Bevacizumab-loaded tetra-PEG gel and 5-Carboxyfluorescein N-succinimidyl ester (FAM-NHS)-labeled IgG-loaded tetra-PEG gel were prepared by mixing tetra-PEG with thiol termini (tetra-PEG-SH) solution, maleimide termini (tetra-PEG-MA) solution, and bevacizumab or FAM-NHS labeled IgG. The gels were prepared with three different polymer concentrations of 1.5%, 5%, and 10%, then an in vitro release study performed to assess the sustained release ability of the drug-loaded tetra-PEG gels. High performance liquid chromatography (HPLC) was used to test the structural stability of the bevacizumab released from the tetra-PEG gel. The binding of bevacizumab to tetra-PEG-SH or MA was assessed using SDS-polyacrylamide gel electrophoresis (PAGE). The bioactivity of released bevacizumab was tested using KDR/NFAT-RE HEK293 cells. In addition, in vitro degradation and swelling studies were also performed. The in vitro release analysis showed that the release of bevacizumab was slower in the 5% and 10% tetra-PEG gels than that of 1.5% tetra-PEG gels. Similarly, the release of FAM-NHS-labeled IgG was slowest in the 1.5%, 5%, and 10% tetra-PEG gels, in that order. The 5% and 10% tetra-PEG gels released bevacizumab and FAM-NHS-labeled IgG over a period of 1-2 weeks. Both bevacizumab and FAM-NHS-labeled IgG were not fully released in 2 weeks. HPLC analysis showed that the retention time of the samples released from the bevacizumab-loaded tetra-PEG gel was similar to that of the bevacizumab standard. The SDS-PAGE analysis showed that bevacizumab binds to tetra-PEG-MA. The bioactivity assay test revealed no decrease in the bioactivity of the released bevacizumab. In vitro degradation and swelling studies revealed that 1.5%, 5%, and 10% tetra-PEG gels expanded by approximately 1.4-, 2-, and 3-fold, respectively. Based on the results of the release and swelling tests, 5% tetra-PEG gels are considered good candidates for controlled release systems for therapeutic antibodies such as bevacizumab. The binding of PEG to the therapeutic antibodies may reduce the availability of therapeutic antibodies that can be released.
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Hidrogeles , Polietilenglicoles , Bevacizumab , Preparaciones de Acción Retardada , Ésteres , Células HEK293 , Humanos , Inmunoglobulina G , Maleimidas/química , Polietilenglicoles/química , Polímeros/química , Compuestos de SulfhidriloRESUMEN
To evaluate the vision-related quality of life (VR-QOL) treated by intravitreal ranibizumab (IVR) in patients with branch retinal vein occlusion (BRVO) and to assess subscale items of the VR-QOL. This was prospective, multicenter, open-label, observational study including 38 patients with unilateral BRVO who underwent IVR treatment and 28 age-matched healthy subjects. VR-QOL using the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) and best-corrected visual acuity (BCVA) were examined before and at 3, 6, and 12 months after treatment. The VFQ-25 composite score and BCVA significantly improved from 3 to 12 months after IVR treatment (P < 0.05), such that there was no significant difference between the BRVO and control groups at 12 months. All subscales of the VFQ-25, except "general health", significantly improved after treatment, while "near vision" and "mental health" were worse than those in healthy subjects (P < 0.05). Patients with superior BRVO had a lower "near vision" score than healthy subjects after treatment (P < 0.05). BCVA in the treated eye and fellow eye had no significant relationship with the VFQ-25 composite score before and after treatment. The VR-QOL of patients with BRVO improved with IVR treatment and was comparable to that of healthy subjects after 12 months. Superior BRVO particularly affected near vision for a low level.
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Ranibizumab , Oclusión de la Vena Retiniana , Inhibidores de la Angiogénesis/uso terapéutico , Humanos , Inyecciones Intravítreas , Estudios Prospectivos , Calidad de Vida , Ranibizumab/uso terapéutico , Agudeza VisualRESUMEN
Visual functions that affect vision-related quality of life (VR-QoL) before and after intravitreal injection of ranibizumab in patients with cystoid macular edema secondary to central retinal vein occlusion (CRVO-CME) are poorly understood. This multicenter, open-label, single-arm prospective study included 23 treatment-naïve patients with CRVO-CME. The best-corrected visual acuity (BCVA), letter contrast sensitivity (LCS), severity of metamorphopsia (M-CHARTS), amount of aniseikonia (New Aniseikonia Test), and stereopsis (Titmus Stereo Test and TNO stereotest) were examined every month from before treatment to 12 months after treatment. For VR-QoL assessment, the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) was provided to the patients before treatment and at 3, 6, and 12 months after treatment. Stepwise multiple regression analysis revealed that the BCVA of the fellow eye was related to the VFQ-25 composite score before treatment, and that the BCVA of the fellow eye and TNO values were related to the VFQ-25 composite score 12 months after treatment. Changes in LCS were significantly correlated with changes in the VFQ-25 composite score. In patients with CRVO-CME, visual acuity of the fellow eye had the strongest impact on VR-QoL. The contrast sensitivity of the affected eye and stereopsis were also associated with VR-QoL.
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PURPOSE: To investigate the clinical features, treatment options, and visual outcomes of submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD). DESIGN: A retrospective, observational case series. METHODS: Setting: Multicenter institutional setting. Patient Population: A total of 127 patients (127 eyes; 88 men, 39 women; (mean age, 74.2 years)) diagnosed with AMD-associated SMHs exceeding 2 disc diameters involving the fovea. Observation: The AMD types, previous treatments, treatment options, anatomic findings, and best-corrected visual acuity (BCVA) were assessed. Main Outcome Measures: Clinical features, treatment options, and visual outcomes of SMHs secondary to nAMD. RESULTS: Thirty-two eyes had typical AMD, 94 eyes polypoidal choroidal vasculopathy (PCV), and one eye retinal angiomatous proliferation. Eighty-five eyes were treatment-naïve; 42 eyes were treated previously: anti-vascular endothelial growth factor (VEGF) therapy (n = 26), photodynamic therapy (n = 3), and combined therapy (n = 13). Treatment of SMHs included vitrectomy (36 eyes), pneumatic displacement (49 eyes), and anti-VEGF monotherapy (42 eyes). The final BCVA improved significantly in treatment-naïve cases from 0.86 to 0.62 logarithm of the minimal angle of resolution (logMAR) unit (Snellen equivalent from 20/145 to 20/83) and from 0.80 to 0.56 (Snellen equivalent from 20/126 to 20/73) in PCV cases. Meanwhile, the BCVA logMAR values improved from 1.15 to 0.75 (Snellen equivalent from 20/283 to 20/112) and from 0.87 to 0.63 (Snellen equivalent from 20/148 to 20/85) in eyes that underwent vitrectomy or pneumatic displacement, respectively. In eyes with BCVAs between 20/133 to 20/40 at SMH onset, the final VA in the pneumatic displacement group was better than in the anti-VEGF monotherapy group. One eye had a retinal detachment and 1 eye had a macular hole in the vitrectomy group, and 5 eyes had a vitreous hemorrhage in the pneumatic displacement group. CONCLUSIONS: The recommended treatment for SMHs secondary to nAMD exceeding 2 disc area and with BCVA below 20/40 is vitrectomy or pneumatic displacement for visual improvement.
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Degeneración Macular , Activador de Tejido Plasminógeno , Anciano , Inhibidores de la Angiogénesis/uso terapéutico , Femenino , Fibrinolíticos/uso terapéutico , Angiografía con Fluoresceína , Humanos , Inyecciones Intravítreas , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/terapia , Masculino , Pronóstico , Hemorragia Retiniana/diagnóstico , Hemorragia Retiniana/etiología , Hemorragia Retiniana/terapia , Estudios Retrospectivos , Activador de Tejido Plasminógeno/uso terapéutico , Tomografía de Coherencia ÓpticaRESUMEN
Background: To investigate the relationship between stereopsis and vision-related quality of life (VR-QOL) in patients with branch retinal vein occlusion (BRVO) before and after treatment with intravitreal ranibizumab (IVR). Methods: This prospective multicentred observational study included 37 patients undergoing IVR treatment for unilateral BRVO and 24 age-matched healthy controls.Stereopsis was evaluated using the TNO stereo test (TNO) and Titmus stereo test (TST) every month, and the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) was administered at baseline, then at 3, 6 and 12 months after treatment. Results: Time course of the changes in stereopsis and VR-QOL. IVR treatment significantly reduced central fovea thickness and improved both the TNO and the TST from 2 to 12 months (both p<0.05). Stereopsis before and after IVR injection in the eyes with BRVO were significantly worse than those in control subjects (TNO, p<0.001; TST, p<0.001). The VFQ-25 composite score significantly improved from 3 to 12 months after IVR treatment (p<0.05). Univariate analysis showed that the TNO score at baseline was significantly correlated with the VFQ-25 composite score at baseline and after treatment (p<0.05, p<0.05, respectively). TST score was not associated with the VFQ-25 composite score at baseline or after treatment. Conclusions: Treatment with IVR for BRVO improved cystoid macular oedema, which was correlated to improved stereopsis, although not to the control level. The TNO score at baseline was associated with VR-QOL in patients with BRVO.
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Oclusión de la Vena Retiniana , Inhibidores de la Angiogénesis/uso terapéutico , Preescolar , Percepción de Profundidad , Humanos , Estudios Prospectivos , Calidad de Vida , Ranibizumab/uso terapéutico , Oclusión de la Vena Retiniana/tratamiento farmacológico , Agudeza VisualRESUMEN
PURPOSE: To quantify stereopsis and other visual functions in patients with unilateral branch retinal vein occlusion (BRVO) and to investigate vision-related parameters that affect stereopsis. DESIGN: Prospective observational study. SUBJECTS: Forty-five patients undergoing intravitreal ranibizumab (IVR) treatment for unilateral BRVO. METHODS: We examined stereopsis using the Titmus stereo test (TST) and TNO stereotest (TNO), best corrected visual acuity (BCVA), letter contrast sensitivity, severity of metamorphopsia and degree of aniseikonia before and 6 months after IVR. MAIN OUTCOME MEASURES: Visual functions that affect stereopsis. RESULTS: Baseline stereopsis in patients with BRVO was 2.7 ± 0.6 (range, 1.6-3.5) in the TST and 2.8 ± 0.5 (range, 1.8-3.3) in TNO. TST and TNO scores were significantly correlated with BCVA and letter contrast sensitivity at baseline (P < 0.001) but not with other visual functions. IVR treatment significantly improved stereopsis, BCVA, and letter contrast sensitivity. After treatment, TST scores were significantly correlated with BCVA (P < 0.001), letter contrast sensitivity (P < 0.001), and aniseikonia (P < 0.01). TNO scores were significantly correlated with BCVA (P < 0.01) and letter contrast sensitivity (P < 0.01). TST and TNO scores after treatment were significantly correlated with BCVA at baseline (P < 0.01 for both). CONCLUSIONS: Deterioration of stereopsis in patients with BRVO was associated with changes in visual acuity and contrast sensitivity after treatment. Initial visual acuity is a prognostic factor for posttreatment stereopsis.
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Aniseiconia , Oclusión de la Vena Retiniana , Inhibidores de la Angiogénesis/uso terapéutico , Percepción de Profundidad , Humanos , Inyecciones Intravítreas , Ranibizumab/uso terapéutico , Oclusión de la Vena Retiniana/tratamiento farmacológico , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Agudeza VisualRESUMEN
The effects of the ultra-high-molecular-weight (UHMW) component of polypropylene (PP) on its rheological properties, crystallization behavior, and solid-state mechanical properties were investigated using various measurement techniques. The terminal relaxation time-determined by measuring the linear viscoelasticity-was increased by adding the UHMW component. The increase in the melt elasticity produced by adding the UHMW component was observed by measuring the steady-state shear flow, although the shear viscosity was not greatly affected. Owing to the long characteristic time of the Rouse relaxation of the UHMW component, PP with the UHMW component formed highly oriented structures through a shear-induced crystallization process. The addition of the UHMW component enhanced the orientation and regularity of crystalline structure for extruded films. Therefore, the Young's modulus, yield stress, and strength were higher in the PP film containing the UHMW component than in one without the UHMW component, irrespective of the direction of tensile deformation.