RESUMO
AIMS: To determine the presence of sectoral changes in vessel density (VD) patterns induced by vascular endothelial growth factor inhibitors (anti-VEGF) in patients with diabetic macular edema (DME) using optical coherence tomography angiography (OCTA). METHODS: Prospective, interventional study. A total of 43 patients (63 eyes) were initially enrolled in the study. We performed swept source (SS) OCT and sectorial OCTA measurement to determine parafoveal VD at baseline and after six months of anti-VEGF treatment. In the locations with statistically significant differences in VD between baseline and month 6, we performed univariate and multivariate analyses to determine which, if any, of the baseline variables were associated with the observed changes. RESULTS: A total of 34 patients (48 eyes) were included in the final analysis. Mean VD decreased from baseline to month 6 (from 45.2 (± 3.5) to 44.6 (± 3.2) % in the SCP and from 50 (± 3.3) to 49 (± 3.9) % in the DCP). The only significant changes in VD were observed in the nasal sector of the deep capillary plexus, with a decrease of 2.9% (p = 0.001). On univariate and multivariate analyses, the only variable significantly associated with changes in VD in the nasal sector after 6 months of treatment was baseline VD in the same sector. CONCLUSIONS: Anti-VEGF therapy has a small impact on VD values over time. These variations observed after treatment seems to be related to changes over areas of vascular anomalies and displaced vessels adjacent to cystic areas, with no significant changes over ischemic areas. No correlation was observed between this trend and other clinical baseline features.
RESUMO
BACKGROUND: The aim of this study was to test the feasibility and safety of subretinal transplantation of human induced pluripotent stem cell (hiPSC)-derived retinal pigment epithelium (RPE) cells into the healthy margins and within areas of degenerative retina in a swine model of geographic atrophy (GA). METHODS: Well-delimited selective outer retinal damage was induced by subretinal injection of NaIO3 into one eye in minipigs (n = 10). Thirty days later, a suspension of hiPSC-derived RPE cells expressing green fluorescent protein was injected into the subretinal space, into the healthy margins, and within areas of degenerative retina. In vivo follow-up was performed by multimodal imaging. Post-mortem retinas were analyzed by immunohistochemistry and histology. RESULTS: In vitro differentiated hiPSC-RPE cells showed a typical epithelial morphology, expressed RPE-related genes, and had phagocytic ability. Engrafted hiPSC-RPE cells were detected in 60% of the eyes, forming mature epithelium in healthy retina extending towards the border of the atrophy. Histological analysis revealed RPE interaction with host photoreceptors in the healthy retina. Engrafted cells in the atrophic zone were found in a patchy distribution but failed to form an epithelial-like layer. CONCLUSIONS: These results might support the use of hiPSC-RPE cells to treat atrophic GA by providing a housekeeping function to aid the overwhelmed remnant RPE, which might improve its survival and therefore slow down the progression of GA.
Assuntos
Atrofia Geográfica , Células-Tronco Pluripotentes Induzidas , Epitélio Pigmentado da Retina , Animais , Antígenos de Diferenciação/biossíntese , Modelos Animais de Doenças , Regulação da Expressão Gênica , Atrofia Geográfica/metabolismo , Atrofia Geográfica/patologia , Atrofia Geográfica/cirurgia , Xenoenxertos , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/patologia , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Epitélio Pigmentado da Retina/transplante , SuínosRESUMO
IMPORTANCE: Treatments for geographic atrophy (GA), a late stage of age-related macular degeneration (AMD), are currently under development. Understanding the natural course is needed for optimal trial design. Although enlargement rates of GA and visual acuity (VA) in the short term are known from clinical studies, knowledge of enlargement in the long term, life expectancy, and visual course is lacking. OBJECTIVE: To determine long-term enlargement of GA. DESIGN, SETTING, AND PARTICIPANTS: In this study, participant data were collected from 4 population-based cohort studies, with up to 25 years of follow-up and eye examinations at 5-year intervals: the Rotterdam Study cohorts 1, 2, and 3 and the Blue Mountains Eye Study. Data were collected from 1990 to 2015, and data were analyzed from January 2019 to November 2020. MAIN OUTCOMES AND MEASURES: Area of GA was measured pixel by pixel using all available imaging. Area enlargement and enlargement of the square root-transformed area, time until GA reached the central fovea, and time until death were assessed, and best-corrected VA, smoking status, macular lesions according to the Three Continent AMD Consortium classification, a modified version of the Wisconsin age-related maculopathy grading system, and AMD genetic variants were covariates in Spearman, Pearson, or Mann-Whitney analyses. RESULTS: Of 171 included patients, 106 (62.0%) were female, and the mean (SD) age at inclusion was 82.6 (7.1) years. A total of 147 of 242 eyes with GA (60.7%) were newly diagnosed in our study. The mean area of GA at first presentation was 3.74 mm2 (95% CI, 3.11-4.67). Enlargement rate varied widely between persons (0.02 to 4.05 mm2 per year), with a mean of 1.09 mm2 per year (95% CI, 0.89-1.30). Stage of AMD in the other eye was correlated with GA enlargement (Spearman ρ = 0.34; P = .01). Foveal involvement was already present in incident GA in 55 of 147 eyes (37.4%); 23 of 42 eyes (55%) developed this after a mean (range) period of 5.6 (3-12) years, and foveal involvement did not develop before death in 11 of 42 eyes (26%). After first diagnosis, 121 of 171 patients with GA (70.8%) died after a mean (SD) period of 6.4 (5.4) years. Visual function was visually impaired (less than 20/63) in 47 of 107 patients (43.9%) at last visit before death. CONCLUSIONS AND RELEVANCE: In this study, enlargement of GA appeared to be highly variable in the general population. More than one-third of incident GA was foveal at first presentation; those with extrafoveal GA developed foveal GA after a mean of 5.6 years. Future intervention trials should focus on recruiting those patients who have a high chance of severe visual decline within their life expectancy.
Assuntos
Atrofia Geográfica , Degeneração Macular , Morte , Feminino , Angiofluoresceinografia , Atrofia Geográfica/diagnóstico , Humanos , Degeneração Macular/diagnóstico , Masculino , Estudos Prospectivos , Acuidade VisualRESUMO
PURPOSE: To evaluate the efficacy and safety profile of Kahook Dual Blade ab interno trabeculectomy combined with phacoemulsification compared to stand-alone conventional cataract surgery. METHODS: A single-center longitudinal, randomized controlled trial was conducted. Patients older than 18 years with coexisting cataract and open-angle glaucoma or ocular hypertension were invited to participate. Preoperative and postoperative clinical data were collected and analyzed preoperatively and at months 1, 3, 6, and 12 after the procedure. Main outcome measures included best corrected visual acuity, intraocular pressure, number of glaucoma medications, endothelial cell count, and standard automated perimetry. RESULTS: Forty-two eyes from 33 patients were randomly allocated to the combined cataract and KDB (treatment, n = 21) or cataract alone (control, n = 21) groups. Intraocular pressure decreased from 17.9 ± 3.5 to 16.0 ± 2.2 mmHg and from 17.3 ± 2.5 to 15 ± 3.2 mmHg at the last visit in the treatment and control groups (p = 0.47). The use of glaucoma medications was reduced from a median (IQR) 1 (1-2) to 0 (0-0) in the treatment group and from 1 (1-2) to 0 (0-1) in the control group, with no significant differences between groups at the 12-month visit (p = 0.47). Best corrected visual acuity, endothelial cell count, and standard automated perimetry remained similar during follow-up in both groups. CONCLUSIONS: In patients with well-controlled, mild-to-moderate glaucoma, adding ab interno trabeculectomy with KDB to phacoemulsification might not be more effective than phacoemulsification alone to reach mid-teens IOP values. Both procedures showed similar safety profiles. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04202562, December 17, 2019 retrospectively registered.
Assuntos
Glaucoma de Ângulo Aberto , Facoemulsificação , Trabeculectomia , Adolescente , Glaucoma de Ângulo Aberto/cirurgia , Humanos , Pressão Intraocular , Estudos Retrospectivos , Resultado do Tratamento , Acuidade VisualRESUMO
IMPORTANCE: To provide new insights into aflibercept effect in non-naive-treated patients with neovascular age-related macular degeneration. PURPOSE: To assess the efficacy of intravitreal aflibercept in patients with neovascular age-related macular degeneration without optimal response to previous anti-vascular endothelial growth factor A therapy. DESIGN: Single-arm, multi-centre, prospective study. PARTICIPANTS: Patients ⩾50 years with active neovascular age-related macular degeneration, best-corrected visual acuity between 20/32 and 20/320 with suboptimal response to ranibizumab or bevacizumab. METHODS: Aflibercept was administered monthly (3-first months), and bimonthly thereafter until month 8. Anatomical and functional outcomes were assessed. MAIN OUTCOME MEASURE: Percentage of eyes without intra or subretinal fluid on optical coherence tomography after 3-monthly loading doses of aflibercept. RESULTS: A total of 46 patients were included. At week 12, 45.7% (95% confidence interval: 31.5%-60.1%) of eyes showed no fluid on optical coherence tomography. The mean (standard deviation) best-corrected visual acuity increased from 65.1 (8.3) to 69.6 (8.1) letters (+4.5 (5.8) p < 0.0001) and was stabilized at week 40 as compared to baseline. Mean central macular thickness decreased from 430 (119) µm to 323 (100) µm at week 12 (-107 (90) µm, p < 0.0001) and was reduced at week 40 (-46 (111) µm, p = 0.0056). At week 40, 21.7% (95% confidence interval: 9.8%-33.7%) had no fluid. There was a case of presumed noninfectious endophthalmitis that was successfully managed. CONCLUSION: Almost half of patients presented no fluid on optical coherence tomography at week 12, and there was a clinically significant improvement in best-corrected visual acuity. At week 40, one in five patients did not show intra or subretinal fluid, central macular thickness decreased and best-corrected visual acuity was stabilized compared to baseline.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Neovascularização de Coroide/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Neovascularização de Coroide/diagnóstico por imagem , Neovascularização de Coroide/fisiopatologia , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Masculino , Estudos Prospectivos , Líquido Sub-Retiniano , Tomografia de Coerência Óptica , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia , Degeneração Macular Exsudativa/diagnóstico por imagem , Degeneração Macular Exsudativa/fisiopatologiaRESUMO
PURPOSE: To establish the dose of subretinal sodium iodate (NaIO3) in order to create a toxin-induced large animal model of selective circumscribed atrophy of outer retinal layers, the retinal pigment epithelium (RPE), and photoreceptors, by spectral-domain optical coherence tomography (SD-OCT) and immunocytochemistry. METHODS: Fifteen male and female healthy Yorkshire pigs received unilateral subretinal escalating doses of NaIO3 under general anesthesia. In all the animals, volumes of 0.1 to 0.2 mL NaIO3 were injected into the subretinal space of the area centralis through a 23/38-gauge subretinal cannula. Control SD-OCTs were performed 1 and 2 months after the surgery, at which time pigs were euthanized and eyes enucleated. Globes were routinely processed for histologic and immunohistochemical evaluation. RESULTS: Spectral-domain OCT and immunohistochemistry revealed circumscribed and well-demarcated funduscopic lesions, limited to the outer retinal layers in pigs treated with 0.01 mg/mL subretinal sodium iodate. CONCLUSIONS: The swine model of a controlled area of circumscribed retinal damage, with well-delimited borders, and selectively of the outer layers of the retina presented herein shows several clinical and histologic features of geographic atrophy in AMD. Therefore, it may represent a valuable tool in the investigation of new emerging regenerative therapies that aim to restore visual function, such as stem cell transplantation or optogenetics.
Assuntos
Atrofia Geográfica/patologia , Iodatos/metabolismo , Epitélio Pigmentado da Retina/patologia , Líquido Sub-Retiniano/química , Tomografia de Coerência Óptica/métodos , Animais , Segmento Anterior do Olho/diagnóstico por imagem , Biomarcadores/metabolismo , Diagnóstico Diferencial , Modelos Animais de Doenças , Progressão da Doença , Feminino , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Atrofia Geográfica/metabolismo , Imuno-Histoquímica , Masculino , Oftalmoscopia/métodos , Degeneração Retiniana/diagnóstico , Suínos , Acuidade VisualAssuntos
Corioide/irrigação sanguínea , Neovascularização de Coroide/diagnóstico , Pólipos/diagnóstico , Epitélio Pigmentado da Retina/patologia , Tomografia de Coerência Óptica , Neovascularização de Coroide/cirurgia , Corantes/administração & dosagem , Angiofluoresceinografia , Humanos , Verde de Indocianina/administração & dosagem , Fotocoagulação a Laser , Masculino , Pessoa de Meia-Idade , Pólipos/cirurgiaRESUMO
PURPOSE: To describe the management of a subfoveal polypoidal choroidal vasculopathy case refractory to antiangiogenic treatment and to photodynamic therapy. METHODS: Case report. A 65-year-old male patient presented with a diagnosis of exudative age-related macular degeneration of his left eye and unsuccessful response to eight antiangiogenic injections. Visual acuity was 20/33. Fluorescein angiography, spectral domain optical coherence tomography, and indocyanine green angiography confirmed the diagnosis of polypoidal choroidal vasculopathy. Two photodynamic therapy sessions along with two ranibizumab injections were performed, but no response was obtained. Identification and photocoagulation of the polyp feeder vessels was performed. RESULTS: Polypoidal structures regressed, intraretinal and subretinal exudation resolved, and visual acuity was preserved with no adverse events. CONCLUSION: Indocyanine green angiography-guided feeder vessel diode laser photocoagulation in selected cases of polypoidal choroidal vasculopathy may be considered an effective alternative therapy, especially in those refractory to both photodynamic therapy and antiangiogenic therapy.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Doenças da Coroide/cirurgia , Fotocoagulação a Laser/métodos , Ranibizumab/uso terapêutico , Vasos Retinianos/cirurgia , Idoso , Terapia Combinada , Humanos , Masculino , Resultado do TratamentoRESUMO
INTRODUCTION: The management of large pigment epithelial detachments (PEDs) associated with retinal angiomatous proliferation (RAP) remains a challenge due to the high risk of retinal pigment epithelial (RPE) tear. We describe the successful progressive anatomical result and the maintenance of visual acuity to bimonthly, half-dose ranibizumab in a patient with this condition. PURPOSE: To describe the management of a large PED secondary to RAP with bimonthly, half-dose ranibizumab. METHOD: Case report. PATIENT: A 71-year-old woman presented with visual symptoms due to an enlarged PED, compared with previous visits, secondary to a RAP lesion, with a visual acuity of 20/32. To reduce the risk of an RPE tear and a significant decrease in vision, we discussed with the patient the possibility of treating the lesion in a progressive manner, with more frequent but smaller doses of ranibizumab. The patient was treated biweekly with 0.25 mg of ranibizumab until fattening of the PED. RESULTS: The large PED fattened progressively, and visual acuity was preserved with no adverse events. DISCUSSION: The use of half-dose antiangiogenic therapy may be useful in managing large vascularized PED associated with RAP, in an attempt to reduce the risk of RPE tear.
RESUMO
OBJECTIVE: To determine whether foveal swelling exists in patients with foveal sparing and geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD) and to establish the contribution of different foveal layers to this condition by use of spectral-domain optical coherence tomography (SD-OCT). DESIGN: Prospective comparative case series. PARTICIPANTS: We assessed patients from a longitudinal study with foveal sparing and GA secondary to AMD. Of an initial sample of 108 patients, 13 eyes of 10 patients complied with the inclusion criteria to study eyes in which apparent swelling would not be questionable. We used a control group of 13 healthy patients to compare the outcome measurements. METHODS: We acquired high-resolution SD-OCT horizontal and oblique B-scans centered at the umbo. Two retinal specialists (J.M., F.T.) independently classified the SD-OCT images. MAIN OUTCOME MEASURES: Difference in foveal center thickness, apparent outer nuclear layer (ONL) thickness, ONL thickness without Henle's fiber layer (HFL), sub-ONL thickness, and retinal thickness at 1000 µm and 3500 µm from the foveal center. RESULTS: The thickness at the foveal center was similar between patients with apparent foveal swelling (cases) and controls without AMD (226 vs. 227 µm; P = 0.56), but the apparent ONL was thicker in cases than in controls (125 vs. 114 µm; P = 0.02). However, when HFL was excluded from the measurements, there was little difference in the results (74 vs. 73 µm; P = 0.82). CONCLUSIONS: We found neither foveal nor ONL swelling in this study. We observed HFL thickening in foveal sparing secondary to GA, which might be related to swelling of the axons of the photoreceptors, or Müller's cells. We also observed thinning of the retina below the external limiting membrane. The clinical significance of these findings should be addressed by longitudinal studies and may have specific therapeutic implications.
Assuntos
Fóvea Central/patologia , Atrofia Geográfica/patologia , Edema Macular/patologia , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Atrofia Geográfica/complicações , Humanos , Edema Macular/etiologia , Masculino , Estudos ProspectivosRESUMO
BACKGROUND: To investigate the safety and efficacy of a combined fixed-interval and pro re nata regimen of ranibizumab (FUSION regimen) for treatment of exudative age-related macular degeneration in patients with good visual acuity at baseline. To establish whether similar efficacy to monthly regimens can be achieved with fewer injections, even in patients with good visual acuity. METHODS: This was a prospective, open-label, consecutive interventional case series in treatment-naïve patients with exudative age-related macular degeneration. The FUSION regimen consists of three phases: 1) a loading phase of two or three injections, depending on presence or absence of choroidal neovascularization activity at first follow-up, 2) administration of one injection on disappearance of exudation, and 3) subsequent administration of two separate injections at intervals 2 months apart, and then an injection every 3 months. Endpoints included visual acuity, presence of fluid, adverse events and number of injections administered. RESULTS: Seventeen eyes of 17 Caucasian patients were included. Mean patient age was 76 years, and 15 patients were female. Mean baseline visual acuity was 67.5 letters (median 67), with Snellen equivalent 20/50++, ranged between 45 (20/125) and 83 (20/20--). At 3 months, mean change in best-corrected visual acuity (BCVA) was +2.3 letters (median +9) compared with baseline (p = 0.3). At 6 months, mean change in BCVA was +4.2 letters (median +9) compared with baseline (p = 0.02). At 12 months, one patient had discontinued the study. Mean change in BCVA was 5.6 (median +10) compared with baseline (p = 0.04). No patient lost ≥15 letters, and 14 patients (87.5%) lost <5 letters. The mean number of injections was 6.9. One patient experienced a retinal pigment epithelium tear; no other complications were observed. CONCLUSIONS: The FUSION regimen for ranibizumab has the potential to maintain visual gains achieved during the loading phase, as reported in studies with monthly injections, even in eyes with a relatively good visual acuity at baseline. These 12-month results warrant validation in a larger, randomized controlled trial.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Acuidade Visual/fisiologia , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Exsudatos e Transudatos , Feminino , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Ranibizumab , Tomografia de Coerência Óptica , Resultado do Tratamento , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/fisiopatologiaRESUMO
PURPOSE: To describe the results obtained in patients with neovascular age-related macular degeneration treated with ranibizumab 0.5 mg on an as-needed basis from the start after 1 year of follow-up. METHODS: Retrospective, consecutive interventional case series of patients with all angiographic types of neovascular age-related macular degeneration (mean baseline size, 3.4 disk areas) in a tertiary retinal center (Institut de la Màcula i la Retina; Barcelona, Spain). Main outcome was mean vision change; secondary outcomes were center retinal thickness change, number of injections, adverse events, and independent covariates associated with a good response. RESULTS: Mean visual acuity change was an increase of 1.3 letters (95% confidence interval -2.7 to +5.3), and difference between angiographic patterns did not reach statistical significance (p=0.30). A decrease in retinal thickness of 44.6 µm was identified (p<0.001), with a median of 3 injections. Absence of baseline arterial hypertension, lower visual acuity, and lesions located outside the fovea were associated with a better response to therapy. CONCLUSIONS: As-needed treatment from the start achieved stabilization of visual acuity and a moderate decrease of retinal thickness with a low number of injections, but did not achieve the same efficacy as regular monthly injections.