RESUMEN
PURPOSE: To evaluate the prognostic impact of hyperreflective foci (HRF) on spectral-domain optical coherence tomography (SD-OCT) in nonsyndromic retinitis pigmentosa (RP). METHODS: Retrospective, single-center cohort study including genetically-tested RP patients with a minimum follow-up of 24 months. Clinical data including demographics, genetic results and best-corrected visual acuity (BCVA) at baseline and follow-up were collected. Horizontal and vertical SD-OCT scans were analyzed by 2 independent graders. Outer nuclear layer (ONL) thickness and ellipsoid zone (EZ) width were manually measured in horizontal and vertical scans. HRF were classified according to location: outer retinal layers within the central 3mm (central-HRF), outer retinal layers beyond the central 3mm (perifoveal-HRF), and choroid (choroidal-HRF). Central macular thickness (CMT), central point thickness (CPT) and choroidal thickness (CT) at baseline and follow-up were also recorded. RESULTS: A total of 175 eyes from 94 RP patients (47.9% female, mean age 50.7±15.5 years) were included, with a mean follow-up of 29.24±7.17 months. Mean ETDRS (early treatment diabetic retinopathy study) BCVA decreased from 61.09±23.54 to 56.09±26.65 (p=0.082). At baseline, 72 eyes (41.1%) showed central-HRF, 110 eyes (62.9%) had perifoveal-HRF and 149 eyes (85.1%) exhibited choroidal-HRF. Central-HRF and perifoveal-HRF were associated with worse final BCVA, as well as greater BCVA deterioration (all p<0.0029). Only central-HRF were associated with a worse final CMT (p<0.001). Shorter EZ widths were associated with all types of HRF (p<0.05). Perifoveal and choroidal-HRF predicted smaller final EZ areas (p<0.01). CONCLUSION: HRF are highly prevalent in RP patients and appear to have a negative prognostic impact in visual function and EZ area.
RESUMEN
PURPOSE: Retinitis pigmentosa (RP) comprises a genetically and clinically heterogeneous group of inherited retinal degenerations, where 20-30% of patients exhibit extra-ocular manifestations (syndromic RP). Understanding the genetic profile of RP has important implications for disease prognosis and genetic counseling. This study aimed to characterize the genetic profile of syndromic RP in Portugal. METHODS: Multicenter, retrospective cohort study. Six Portuguese healthcare providers identified patients with a clinical diagnosis of syndromic RP and available genetic testing results. All patients had been previously subjected to a detailed ophthalmologic examination and clinically oriented genetic testing. Genetic variants were classified according to the American College of Medical Genetics and Genomics; only likely pathogenic or pathogenic variants were considered relevant for disease etiology. RESULTS: One hundred and twenty-two patients (53.3% males) from 100 families were included. Usher syndrome was the most frequent diagnosis (62.0%), followed by Bardet-Biedl (19.0%) and Senior-Løken syndromes (7.0%). Deleterious variants were identified in 86/100 families for a diagnostic yield of 86.0% (87.1% for Usher and 94.7% for Bardet-Biedl). A total of 81 genetic variants were identified in 25 different genes, 22 of which are novel. USH2A and MYO7A were responsible for most type II and type I Usher syndrome cases, respectively. BBS1 variants were the cause of Bardet-Biedl syndrome in 52.6% of families. Best-corrected visual acuity (BCVA) records were available at baseline and last visit for 99 patients (198 eyes), with a median follow-up of 62.0 months. The mean BCVA was 56.5 ETDRS letters at baseline (Snellen equivalent ~ 20/80), declining to 44.9 ETDRS letters (Snellen equivalent ~ 20/125) at the last available follow-up (p < 0.001). CONCLUSION: This is the first multicenter study depicting the genetic profile of syndromic RP in Portugal, thus contributing toward a better understanding of this heterogeneous disease group. Usher and Bardet-Biedl syndromes were found to be the most common types of syndromic RP in this large Portuguese cohort. A high diagnostic yield was obtained, highlighting current genetic testing capabilities in providing a molecular diagnosis to most affected individuals. This has major implications in determining disease-related prognosis and providing targeted genetic counseling for syndromic RP patients in Portugal.
Asunto(s)
Pruebas Genéticas , Mutación , Retinitis Pigmentosa , Humanos , Retinitis Pigmentosa/genética , Retinitis Pigmentosa/diagnóstico , Retinitis Pigmentosa/epidemiología , Portugal/epidemiología , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Adolescente , Adulto Joven , Niño , Anciano , Linaje , Síndromes de Usher/genética , Síndromes de Usher/diagnóstico , Síndromes de Usher/epidemiología , Preescolar , Análisis Mutacional de ADN , Estudios de Seguimiento , ADN/genética , Proteínas del Ojo/genéticaRESUMEN
INTRODUCTION: New insights on polypoidal choroidal vasculopathy (PCV) have shed light regarding its pathophysiology and associations. However, PCV characterization is still incomplete in Caucasians, which is due to presumed lower prevalence in this population. Features typically associated with AMD such as drusen, retinal pigmentary changes or atrophy are seen in PCV, as precursors and in the fellow eye. Pachychoroid spectrum, predisposing to PCV, also presents with chronic changes in the retinal pigment epithelium (RPE), such as drusen-like deposits (DLD), and in the choroid. The purpose of this study is to perform a multimodal imaging characterization of unaffected fellow eyes in a sample of Caucasian patients with unilateral PCV. METHODS: Multicenter retrospective cohort study with a sample of 55 unaffected fellow eyes from patients diagnosed with unilateral PCV confirmed by indocyanine green angiography. The sample was characterized in the baseline by color fundus photography, spectral domain optical coherence tomography (SD-OCT), fluorescein angiography and indocyanine green angiography. Morphological characteristics of both the retina and the choroid were evaluated. The SD-OCT of the last follow-up visit was also evaluated in order to exclude evolution to PCV or choroidal neovascularization. All images captured underwent evaluation by two independent graders. Informed consent was obtained from all participants. RESULTS: Fifty-five patients (median age, 74 ± 15 years) were included. After 15.5 ± 6.4 months of follow-up, only one developed disease (1.9%). Soft and/or hard drusen were present in 60% and pachydrusen in 23.6%. Pachychoroid signs were present in 47.2%, the double-layer sign in 36.4%, disruption of the RPE changes in 16.4% and RPE atrophy in 10.9%. ICGA revealed choroidal vascular dilation in 63.6% and punctiform hyperfluorescence in 52.7%. Branching vascular networks were identified in only 1.9% of cases. CONCLUSION: The identification of pachychoroid signs in the OCT and ICGA were present in over half of the cases and the presence of the double-layer sign in more than a third provide crucial insights for enhanced characterization of this pathology and deeper understanding of its pathogenesis. These findings contribute significantly to the current knowledge, offering valuable markers to discern various phases of the pathology's progression.
Asunto(s)
Neovascularización Coroidal , Vasculopatía Coroidea Polipoidea , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Atrofia/complicaciones , Atrofia/patología , Coroides/patología , Neovascularización Coroidal/diagnóstico , Neovascularización Coroidal/patología , Colorantes , Angiografía con Fluoresceína/métodos , Verde de Indocianina , Vasculopatía Coroidea Polipoidea/diagnóstico por imagen , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodosRESUMEN
PURPOSE: Phenotypic heterogeneity with variable severity has been reported in female carriers of retinitis pigmentosa GTPase regulator (RPGR) mutations, including a male-type phenotype. A phenomenon not fully understood is peripapillary retinal nerve fiber layer (pRNFL) thickening in male patients with RPGR-associated X-linked retinitis pigmentosa, especially in the temporal sector. We aim to describe the genetic spectrum, retinal phenotypes, and pRNFL thickness in a cohort of Caucasian RPGR-mutation heterozygotes. METHODS: A cross-sectional study was conducted at an inherited retinal degeneration (IRD) reference center in Portugal. Female patients heterozygous for clinically significant RPGR variants were identified using the IRD-PT registry. A complete ophthalmologic examination was performed, complemented by macular and peripapillary spectral domain optical coherence tomography (SD-OCT), ultra-widefield color fundus photography (UW-CFP), and ultra-widefield fundus autofluorescence (UW-FAF). The retinal phenotypes were graded according to previously described classifications. The pRNFL thickness across the superior, inferior, nasal, and temporal quadrants was compared to the Spectralis® RNFL age-adjusted reference database. RESULTS: Forty-eight eyes from 24 females (10 families) were included in the study. Genetic analysis yielded 8 distinct clinically significant frameshift variants in RPGR gene, 3 of which herein reported for the first time. No association was found between mutation location and best-corrected visual acuity (BCVA) or retinal phenotype. Age was associated with worse BCVA and more advanced phenotypes on SD-OCT, UW-CFP, and UW-FAF. Seven women (29.17%) presented a male-type phenotype on UW-FAF in at least one eye. An association was found between UW-FAF and pRNFL thickness in the temporal sector (p = 0.003), with the most advanced fundus autofluorescence phenotypes showing increased pRNFL thickness in this sector. CONCLUSION: This study expands the genetic landscape of RPGR-associated disease by reporting 3 novel clinically significant variants. We have shown that clinically severe phenotypes are not uncommon among female carriers. Furthermore, we provide novel insights into pRNFL changes observed in RPGR heterozygotes that mimic what has been reported in male patients.
Asunto(s)
Degeneración Retiniana , Retinitis Pigmentosa , Femenino , Humanos , Masculino , Estudios Transversales , Proteínas del Ojo/genética , Heterocigoto , Fenotipo , Retina , Retinitis Pigmentosa/diagnóstico , Retinitis Pigmentosa/genética , Tomografía de Coherencia Óptica/métodos , Fibras Nerviosas , Neuronas RetinianasRESUMEN
PURPOSE: Retinitis pigmentosa (RP) corresponds to a group of inherited retinal disorders where progressive rod-cone degeneration is observed. Cystoid macular edema (CME) and vitreomacular interface disorders (VMID) are known to complicate the RP phenotype, challenging an age-old concept of retained central visual acuity. The reported prevalence of these changes varies greatly among different studies. We aim to describe the frequency of CME and VMID and identify predictors of these changes in a cohort of Caucasian patients with genetically solved syndromic (sRP) and non-syndromic RP (nsRP). METHODS: Cross-sectional study of patients with genetically solved sRP or nsRP. Genetic testing was clinically oriented in all probands and coordinated by a medical geneticist. The presence/absence of CME and VMIDs such as epiretinal membrane (ERM), vitreomacular traction (VMT), lamellar hole (LH), macular hole (MH), and macular pseudohole (MPH), and the integrity of the neurosensory retina and retinal pigment epithelium were evaluated in individual macular SD-OCT b-scans. Mixed-effects regression analysis models were used to identify significant predictors of BCVA, CME, and VMID. Significance was considered at α < 0.05. RESULTS: We included 250 eyes from 125 patients. Mean age was 44.9 ± 15.7 years and 55.2% were male. Eighty-eight patients had nsRP and 37 had sRP. Median BCVA was 0.5 (0.2-1.3) logMAR. CME was found in 17.1% of eyes, while ERM was found in 54.3% of eyes. The frequency of CME (p = 0.45) and ERM (p = 0.07) did not differ between sRP and nsRP patients, nor across different inheritance patterns. Mixed-effects univariate linear regression identified age (p = 0.04), cataract surgery (p < 0.01), and loss of integrity of outer retinal layers (p < 0.01) as significant predictors of lower visual acuity, while increased foveal thickness (p < 0.01) and the presence of CME (p = 0.04) were predictors of higher visual acuity. On mixed-effects multivariable analysis, only increased foveal thickness was significantly associated with better visual acuity (p < 0.01). CONCLUSION: We found that the burden of ERM and CME in RP patients is high, highlighting the importance of screening for these potentially treatable conditions to improve the quality of life of RP patients.
Asunto(s)
Membrana Epirretinal , Edema Macular , Retinitis Pigmentosa , Estudios Transversales , Femenino , Humanos , Masculino , Calidad de Vida , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Agudeza VisualRESUMEN
PURPOSE: Sector retinitis pigmentosa (RP) is a rare form of rod-cone degeneration typically associated with mutations in the RHO gene. We describe six unrelated patients presenting with this atypical phenotype in association with biallelic mutations in EYS gene. METHODS: Multinational, multicentre cross-sectional case series. Patients with biallelic disease-causing variants in EYS and a clinical diagnosis of sector RP were recruited from specialized centres in Portugal and Brazil. All patients underwent a comprehensive ophthalmologic examination complemented by deep phenotyping. Peripheral blood samples were collected from all probands and available relatives for genetic analysis. Genetic counselling was provided to all subjects. RESULTS: Seven disease-causing variants (4 pathogenic; 3 likely pathogenic) were identified in 6 unrelated female patients. Best-corrected visual acuity ranged from 75 to 85 ETDRS letters. All eyes showed bilateral and symmetrical areas of outer retinal atrophy distributed along the inferior vascular arcades and extending temporally and/or nasally in a crescent-shaped pattern. On fundus autofluorescence (AF), a foveal-sparing curvilinear band of hyperAF encroaching the optic nerve head and extending temporally was seen in 4 patients. The remaining 2 presented bilateral and symmetrical patches of hypoAF inside crescent-shaped areas of hyperAF along the inferior temporal vascular arcade. Visual field testing revealed superior visual field defects of varying extents, always in close association with the fundus AF findings. CONCLUSIONS: Even though EYS has only recently been listed as a cause of the sector RP phenotype, we believe that this presentation is not infrequent and should be considered an important differential for sector RP.
Asunto(s)
Distrofias de Conos y Bastones , Retinitis Pigmentosa , Estudios Transversales , Análisis Mutacional de ADN , Proteínas del Ojo/genética , Femenino , Humanos , Mutación , Retinitis Pigmentosa/diagnóstico , Retinitis Pigmentosa/genéticaRESUMEN
INTRODUCTION: The purpose of this study was to compare clinical/demographic functional testing and multimodal imaging features between genetically solved and genetically unsolved nonsyndromic retinitis pigmentosa (nsRP) patients. METHODS: A cross-sectional study was conducted at an inherited retinal dystrophies reference center. Consecutive patients with nsRP and available genetic testing results performed between 2018 and 2020 were included. Genetic testing was clinically oriented, and variants were classified according to the American College of Medical Genetics and Genomics. Only class IV or V variants were considered disease-causing. Clinical/demographic, functional, and imaging features were compared between genetically unsolved (G1) and genetically solved (G2) patients. RESULTS: A total of 175 patients (146 families) were included: 68 patients (59 families) in G1 and 107 patients (87 families) in G2. First symptoms <25 years, consanguinity, evidence for a particular inheritance pattern, and the absence of indicators for phenocopies were significantly more prevalent in G2. No significant differences were observed on best-corrected visual acuity. The visual field index and mean central retinal layer thickness were significantly higher in G1. The frequency of atypical features on multimodal imaging did not differ between groups. CONCLUSION: Individual clinical/demographic functional testing and multimodal imaging features should be considered when counseling patients about the probability of identifying disease-causing variants.
Asunto(s)
Retinitis Pigmentosa , Estudios Transversales , Demografía , Humanos , Imagen Multimodal , Mutación , Fenotipo , Retinitis Pigmentosa/diagnóstico , Retinitis Pigmentosa/genéticaRESUMEN
IMPORTANCE: Polypoidal choroidal vasculopathy (PCV) is far less common and studied in a Caucasian population than in an Asian population, and the optimal treatment approach remains to be confirmed. METHODS: A 52-week, double-masked, sham-controlled, phase 4, investigator-initiated randomized clinical trial (RCT) in naive symptomatic Caucasian patients with PCV treated with aflibercept in a treat-and-extend regimen (T&E) (intravitreal aflibercept injection [IVAI] T&E). Patients were randomized at week 16 to receive IVAI T&E plus either sham photodynamic therapy (PDT) or standard fluence PDT with verteporfin. The main outcome measures were changes in best-corrected visual acuity (BCVA) from baseline to 52 weeks and polyp occlusion at week 52. Data are presented as median (interquartile range [IQR]) for BCVA, number of IVAI, and change in central retinal thickness (CRT). RESULTS: Of the 50 patients included in the study, 48 patients completed the 52 weeks of follow-up. During this period, a significant median (IQR) BCVA gain of 6 [2-12] Early Treatment Diabetic Retinopathy Study letters was observed for all patients (p < 0.001), after 8 (7-9) injections, with a significant reduction of -93.0 [-154.0, -44.0] µm in central macular thickness (p < 0.001). Using indocyanine green angiography, a complete occlusion of polypoidal lesions was documented in 72% of the cases. Still, no significant difference was detected between the sham PDT and the aflibercept PDT arms, at week 52, for BCVA change (6.5 [2-11] vs. 5 [2-13] letters (p = 0.98)), number of IVAIs (8.5 [7-9] vs. 8 [7-9] (p = 0.21)), change in CRT (-143 [-184; -47] vs. -89 [-123; -41.5] µm [p = 0.23]), and rates of complete polyp occlusion: 77 versus 68% (p = 0.53) or presence of fluid: 68 versus 57% (p = 0.56). No serious ocular adverse events were registered in the 2 arms. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first RCT to compare aflibercept T&E monotherapy with aflibercept T&E plus verteporfin PDT in a Caucasian population with PCV. Aflibercept monotherapy in a T&E showed to be effective and safe with a significant median BCVA improvement of 6 letters and a complete occlusion of polypoidal lesions in near 3 quarters of the eyes, at 1 year. As only 22% of the eyes underwent PDT treatment, the benefit of combined treatment for PCV in Caucasian patients could not be definitively elucidated from this study. TRIAL REGISTRATION: The clinical trial was registered in ClinicalTrials.gov Identifier NCT02495181 and the European Union Drug Regulating Authorities Clinical Trials Database EudraCT No. 2015-001368-20.
Asunto(s)
Fotoquimioterapia , Pólipos , Inhibidores de la Angiogénesis , Coroides/patología , Humanos , Inyecciones Intravítreas , Fármacos Fotosensibilizantes/uso terapéutico , Pólipos/diagnóstico , Pólipos/tratamiento farmacológico , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión/uso terapéutico , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Agudeza VisualRESUMEN
PURPOSE: The aim of the study was to characterize the morphological features of polypoidal choroidal vasculopathy (PCV) in a large Caucasian population. METHODS: We conducteda multicenter, cross-sectional study of treatment-naïve patients with PCV. Baseline fundus photography, spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography (FA), and indocyanine green angiography (ICGA) were assessed by trained medical graders. Typical PCV features were explored, and retinal thickness (RT) and choroidal thickness (CT) measurements were performed. RESULTS: Seventy-nine eyes of 73 patients (mean age, 72.6 ± 11.9 years) were included. ICGA identified macular polyps in 89.9% of cases. SD-OCT revealed mostly subretinal fluid (93.6%) and a retinal pigment epithelium (RPE) detachment in 91.4%, with sharp protrusion in 67.0% of cases. Polyp-like structures were seen in 74.3% of cases, mostly adherent to an elevated RPE (69.6%). Type 1 neovascularization (NV) was identified in 74.7% of patients, while 16.5% had a mixed NV. The mean macular CT was 220.9 ± 83.2 µm (range, 67.9-403.6). Diffuse and focal pachychoroid were observed in 26.6 and 30.4% of patients, respectively. Soft drusen were reported in 62.0% of cases, but retinal hemorrhage occurred in only 19.0% of cases. CONCLUSION: The morphological features of PCV in Caucasians are similar to those reported in Asians. Pachychoroid signs were found in nearly half of our cohort. However, the mean age at presentation, high prevalence of soft drusen, and low prevalence of large subretinal hemorrhages make PCV closer to age-related macular degeneration in this ethnic group.
Asunto(s)
Neovascularización Coroidal , Pólipos , Anciano , Anciano de 80 o más Años , Coroides/patología , Neovascularización Coroidal/patología , Colorantes , Estudios Transversales , Angiografía con Fluoresceína , Humanos , Verde de Indocianina , Persona de Mediana Edad , Pólipos/diagnóstico , Estudios Retrospectivos , Tomografía de Coherencia ÓpticaRESUMEN
Biofluid biomarkers of age-related macular degeneration (AMD) are still lacking, and their identification is challenging. Metabolomics is well-suited to address this need, and urine is a valuable accessible biofluid. This study aimed to characterize the urinary metabolomic signatures of patients with different stages of AMD and a control group (>50 years). It was a prospective, cross-sectional study, where subjects from two cohorts were included: 305 from Coimbra, Portugal (AMD patients n = 252; controls n = 53) and 194 from Boston, United States (AMD patients n = 147; controls n = 47). For all participants, we obtained color fundus photographs (for AMD staging) and fasting urine samples, which were analyzed using 1H nuclear magnetic resonance (NMR) spectroscopy. Our results revealed that in both cohorts, urinary metabolomic profiles differed mostly between controls and late AMD patients, but important differences were also found between controls and subjects with early AMD. Analysis of the metabolites responsible for these separations revealed that, even though distinct features were observed for each cohort, AMD was in general associated with depletion of excreted citrate and selected amino acids at some stage of the disease, suggesting enhanced energy requirements. In conclusion, NMR metabolomics enabled the identification of urinary signals of AMD and its severity stages, which might represent potential metabolomic biomarkers of the disease.
Asunto(s)
Biomarcadores/orina , Líquidos Corporales/metabolismo , Degeneración Macular/orina , Metabolómica , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Degeneración Macular/diagnóstico por imagen , Degeneración Macular/patología , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: To evaluate the macular and peripapillary morpho-vascular changes in ADOA, using optical coherence tomography (OCT) and OCT angiography (OCTA). METHODS: Prospectively defined, cross-sectional case-control study. Consecutive patients with a genetic or clinical diagnosis of ADOA along with age- and sex-matched controls were included. The radial peripapillary capillary (RPC) density and vessel density (VD) in the parafoveal superficial and deep capillary plexuses (SCP and DCP, respectively) were evaluated with OCTA. The ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL) thickness were determined using structural OCT. We applied a previously validated customized macro (Fiji, SciJava Consortium) to compute RPC density. The remaining parameters were calculated by the built-in software. Non-parametric methods were used for data analysis. The target α level was 0.05, which was adjusted through Bonferroni's correction when multiple outcomes were tested. RESULTS: Fifty-eight eyes (n = 29 control; n = 29 ADOA) from 30 subjects (mean age 42.43 ± 15.30 years; 37.93% male) were included. Parafoveal SCP VD, GCC thickness, RPC VD in the temporal quadrant, as well as RNFL thickness in the nasal and temporal quadrants were decreased in ADOA eyes (all p < 0.001). When only patients with genetically confirmed diagnosis were included, capillary dropout in the circumpapillary superior and inferior quadrants also became evident (both p < 0.001). The GCC/parafoveal SCP ratio was increased in ADOA, relatively to matched controls. In contrast, none of the circumpapillary morpho-vascular ratios was significantly different in ADOA eyes. CONCLUSIONS: The microvascular and structural changes found in ADOA suggest that both the macular and peripapillary regions are involved, although the threshold for damage of the structural and vascular components may be different for each region. Larger series with longitudinal follow-up may validate OCTA biomarkers helpful for disease monitoring.
Asunto(s)
Angiografía con Fluoresceína/métodos , Pruebas Genéticas/métodos , Mácula Lútea/patología , Atrofia Óptica Autosómica Dominante/diagnóstico , Disco Óptico/patología , Vasos Retinianos/patología , Tomografía de Coherencia Óptica/métodos , Adolescente , Adulto , Estudios de Casos y Controles , Estudios Transversales , Femenino , Fondo de Ojo , Humanos , Masculino , Persona de Mediana Edad , Atrofia Óptica Autosómica Dominante/genética , Estudios Prospectivos , Adulto JovenRESUMEN
PURPOSE: To study radial peripapillary capillary (RPC) density in the early stages of diabetic retinopathy (DR), using optical coherence tomography angiography. METHODS: A cross-sectional evaluation of RPCs was performed using optical coherence tomography angiography (Avanti RTVue-XR 100, Optovue Inc, Fremont, CA). Annular RPC density was the primary outcome. Global density and retinal nerve fiber layer thickness were secondary outcomes. Diabetic eyes were divided into three groups: no DR, mild nonproliferative DR (mild NPDR), and moderate NPDR. Multilevel mixed-effects univariate and multivariate linear regression models were used. RESULTS: We included 155 eyes (n = 42 control; n = 27 no DR; n = 28 mild NPDR; and n = 58 moderate NPDR) from 86 subjects (mean [SD] age 63.39 [10.70] years; 46.45% male). When compared with controls, a significant decrease in annular RPC density was found in all groups of diabetic eyes on multivariate analysis (no DR: ß = -2.95, P < 0.001; mild NPDR: ß = -1.76, P = 0.017; and moderate NPDR: ß = -2.82, P < 0.001). We also detected a significant decrease in retinal nerve fiber layer thickness in diabetic eyes (even in the no DR group). Furthermore, in diabetic eyes, annular RPC density and retinal nerve fiber layer thickness correlated significantly (R = 0.4874, P < 0.001). CONCLUSION: Peripapillary neurovascular changes occur early in the course of DR. Their significance in the progression of DR warrants further research.
Asunto(s)
Retinopatía Diabética/fisiopatología , Acoplamiento Neurovascular/fisiología , Disco Óptico/irrigación sanguínea , Vasos Retinianos/fisiopatología , Anciano , Capilares/fisiopatología , Estudios de Casos y Controles , Estudios Transversales , Retinopatía Diabética/diagnóstico por imagen , Femenino , Angiografía con Fluoresceína , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Vasos Retinianos/diagnóstico por imagen , Encuestas y Cuestionarios , Tomografía de Coherencia Óptica , Agudeza VisualRESUMEN
PURPOSE: To characterize the plasma metabolomic profile of patients with age-related macular degeneration (AMD) using mass spectrometry (MS). DESIGN: Cross-sectional observational study. PARTICIPANTS: We prospectively recruited participants with a diagnosis of AMD and a control group (>50 years of age) without any vitreoretinal disease. METHODS: All participants underwent color fundus photography, used for AMD diagnosis and staging, according to the Age-Related Eye Disease Study classification scheme. Fasting blood samples were collected and plasma was analyzed by Metabolon, Inc. (Durham, NC), using ultrahigh-performance liquid chromatography (UPLC) and high-resolution MS. Metabolon's hardware and software were used to identify peaks and control quality. Principal component analysis and multivariate regression were performed to assess differences in the metabolomic profiles of AMD patients versus controls, while controlling for potential confounders. For biological interpretation, pathway enrichment analysis of significant metabolites was performed using MetaboAnalyst. MAIN OUTCOME MEASURES: The primary outcome measures were levels of plasma metabolites in participants with AMD compared with controls and among different AMD severity stages. RESULTS: We included 90 participants with AMD (30 with early AMD, 30 with intermediate AMD, and 30 with late AMD) and 30 controls. Using UPLC and MS, 878 biochemicals were identified. Multivariate logistic regression identified 87 metabolites with levels that differed significantly between AMD patients and controls. Most of these metabolites (82.8%; n = 72), including the most significant metabolites, belonged to the lipid pathways. Analysis of variance revealed that of the 87 metabolites, 48 (55.2%) also were significantly different across the different stages of AMD. A significant enrichment of the glycerophospholipids pathway was identified (P = 4.7 × 10-9) among these metabolites. CONCLUSIONS: Participants with AMD have altered plasma metabolomic profiles compared with controls. Our data suggest that the most significant metabolites map to the glycerophospholipid pathway. These findings have the potential to improve our understanding of AMD pathogenesis, to support the development of plasma-based metabolomics biomarkers of AMD, and to identify novel targets for treatment of this blinding disease.
Asunto(s)
Lípidos/sangre , Metabolómica/métodos , Degeneración Macular Húmeda/sangre , Anciano , Biomarcadores/sangre , Estudios Transversales , Femenino , Humanos , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Degeneración Macular Húmeda/diagnósticoRESUMEN
PURPOSE: To investigate the association between dysphotopsia and neural responses in visual and higher-level cortical regions in patients who recently received multifocal intraocular lens (IOL) implants. DESIGN: Cross-sectional study. PARTICIPANTS: Thirty patients 3 to 4 weeks after bilateral cataract surgery with diffractive IOL implantation and 15 age- and gender-matched control subjects. METHODS: Functional magnetic resonance imaging (fMRI) was performed when participants viewed low-contrast grating stimuli. A light source surrounded the stimuli in half of the runs to induce disability glare. Visual acuity, wavefront analysis, Quality of Vision (QoV) questionnaire, and psychophysical assessment were performed. MAIN OUTCOME MEASURES: Cortical activity (blood oxygen level dependent [BOLD] signal) in the primary visual cortex and in higher-level brain areas, including the attention network. RESULTS: When viewing low-contrast stimuli under glare, patients showed significant activation of the effort-related attention network in the early postoperative period, involving the frontal, middle frontal, parietal frontal, and postcentral gyrus (multisubject random-effects general linear model (GLM), P < 0.03). In contrast, controls showed only relative deactivation (due to lower visibility) of visual areas (occipital lobe and middle occipital gyrus, P < 0.03). Patients also had relatively stronger recruitment of cortical areas involved in learning (anterior cingulate gyrus), task planning, and solving (caudate body). Patients reporting greater symptoms induced by dysphotic symptoms showed significantly increased activity in several regions in frontoparietal circuits, as well as cingulate gyrus and caudate nucleus (q < 0.05). We found no correlation between QoV questionnaire scores and optical properties (total and higher order aberration, modulation transfer function, and Strehl ratio). CONCLUSIONS: This study shows the association between patient-reported subjective difficulties and fMRI outcomes, independent of optical parameters and psychophysical performance. The increased activity of cortical areas dedicated to attention (frontoparietal circuits), to learning and cognitive control (cingulate), and to task goals (caudate) likely represents the beginning of the neuroadaptation process to multifocal IOLs.
Asunto(s)
Adaptación Psicológica/fisiología , Deslumbramiento , Implantación de Lentes Intraoculares , Lentes Intraoculares , Facoemulsificación , Trastornos de la Visión/fisiopatología , Corteza Visual/fisiología , Anciano , Sensibilidad de Contraste/fisiología , Estudios Transversales , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Satisfacción del Paciente , Estudios Prospectivos , Diseño de Prótesis , Seudofaquia/fisiopatología , Encuestas y Cuestionarios , Trastornos de la Visión/diagnóstico por imagen , Agudeza Visual/fisiología , Corteza Visual/diagnóstico por imagenRESUMEN
PURPOSE: To compare endothelial cell (EC) variation after anterior chamber phakic intraocular lens (AC-pIOL) implantation in highly myopic patients with a preoperative anterior chamber depth (ACD) between 2.8 and 3.0 versus ≥3.0 mm. METHODS: A total of 280 eyes submitted to primary AC-pIOL implantation were analyzed. Pre- and postoperative values for uncorrected distance visual acuity, corrected distance visual acuity, spherical equivalent, ACD (endothelial surface), and EC count were collected. The eyes were divided into 2 groups: group A - ACD between 2.8 and 3.0 mm; group B - ACD ≥3.0 mm. Mean global EC loss (ECL) and loss for each ACD group, according to pIOL type, were analyzed. RESULTS: Significant improvement of the spherical equivalent (-11.38 ± 4.57 vs. -0.49 ± 0.79; p = 0.000) and a significant decrease in EC density (2,810.95 ± 343.88 vs. 2,584.09 ± 374.88 cells/mm2; p = 0.000) were noted. The mean annual ECL was -2.19 ± 3.97%. Regarding group A (n = 80), a mean annual ECL of -2.06 ± 3.88% was registered, higher for the Acrysof Cachet® subtype, while group B (n = 200) showed -2.25 ± 4.01% ECL, higher for the Verisyse® subtype. There was no significant difference between the groups (p = 0.96). CONCLUSIONS: AC-pIOL implantation significantly improves the spherical equivalent in myopic patients. The mean annual ECL after pIOL implantation was higher in the larger ACD group, but this value was not statistically significant. A 2.8-mm ACD value seems to be a safe cutoff for AC-pIOL implantation.
Asunto(s)
Cámara Anterior/diagnóstico por imagen , Implantación de Lentes Intraoculares/métodos , Miopía Degenerativa/cirugía , Lentes Intraoculares Fáquicas , Refracción Ocular/fisiología , Adulto , Recuento de Células , Endotelio Corneal/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Miopía Degenerativa/diagnóstico , Miopía Degenerativa/fisiopatología , Diseño de Prótesis , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
To analyze photorefractive keratectomy (PRK) outcomes in myopia and myopic astigmatism correction using the WaveLight Allegretto Wave Eye-Q(®) excimer laser system (WaveLight Laser Technologie AG, Erlangen, Germany). 222 eyes of 151 patients underwent PRK (mean age 33.5 ± 6.8 years). Pre-operative best spectacle-corrected visual acuity (BSCVA) ranged from 0.4 to -0.1 logMAR (mean -0.03 ± 0.06). Mean spherical equivalent (SE) was -3.29 ± 1.20 D. Efficacy, predictability and safety were evaluated. Minimum follow-up was 3 months. Accountability at 3 and 6 months was 100 and 54 %, respectively (median follow-up 5 months, mean 5.2 ± 2.6 months). At 3 months, mean uncorrected visual acuity (UCVA) was -0.02 ± 0.07 logMAR, BSCVA -0.03 ± 0.05 logMAR, efficacy index 0.98 and safety index 1.02. UCVA was ≥20/16 in 40.1 %, ≥20/20 in 86.5 % and ≥20/25 in 98.2 %. Mean SE was -0.02 ± 0.20 D. Residual refractive error was ± 0.13 D in 81.5 %, ± 0.25 D in 88.7 % and ± 0.50 D in 97.7 %. At 6 months, outcomes were similar: mean UCVA was -0.02 ± 0.07 logMAR, BSCVA -0.03 ± 0.06 logMAR, efficacy index 1.00 and safety index 1.03. UCVA was ≥20/16 in 43.7 %, ≥20/20 in 86.6 % and ≥20/25 in 96.6 %. Mean SE was -0.02 ± 0.17 D. Residual refractive error was ± 0.13 D in 86.6 %, ± 0.25 D in 93.3 % and ± 0.50 D in 98.3 %. Refractive stability was achieved at 3 months. No patient lost more than one line of BSCVA. There were no retreatments. The WaveLight Allegretto Wave Eye-Q is effective, predictable and safe in low-to-moderate myopia and myopic astigmatism PRK correction.
Asunto(s)
Astigmatismo/cirugía , Láseres de Excímeros/uso terapéutico , Queratectomía Fotorrefractiva/métodos , Adulto , Anciano , Análisis de Varianza , Astigmatismo/fisiopatología , Córnea/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Miopía , Refracción Ocular/fisiología , Estudios Retrospectivos , Agudeza Visual/fisiologíaRESUMEN
PURPOSE: The purpose of this study was to assess the use of topical tacrolimus ointment in preventing rejection in high-risk corneal grafts, when added to the standard immunosuppressive regimen. METHODS: We conducted an observational, retrospective study using clinical data of high-risk patients subjected to penetrating keratoplasty, who were treated with topical tacrolimus ointment 0.2â mg/g twice a day plus topical dexamethasone 0.1â mg/ml 6 id and compared it with a similar control group treated with topical dexamethasone 0.1â mg/ml 6 id alone. High-risk status was attributed to patients with previous ipsilateral corneal graft failure, two or more quadrants with corneal neovascularization or an infectious or inflammatory corneal disease. RESULTS: We analysed 53 patients in the trial group versus 53 patients in the control group, with similar age, baseline diagnosis and risk factors, and median follow-up times of 30 and and 24 months, respectively. Survival analysis showed a higher graft survival rate at all follow-up periods for patients treated with topical tacrolimus (p < 0.01). No adverse reactions were reported. DISCUSSION: This study shows that topical tacrolimus ointment increases the survival rate of the graft if added to the previous topical steroid regimen in high-risk patients. CONCLUSION: Topical tacrolimus is safe and effective in prolonging graft survival in high-risk patients.
Asunto(s)
Enfermedades de la Córnea , Trasplante de Córnea , Humanos , Tacrolimus/uso terapéutico , Estudios Retrospectivos , Pomadas/uso terapéutico , Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Queratoplastia Penetrante , Enfermedades de la Córnea/tratamiento farmacológico , Enfermedades de la Córnea/cirugía , Dexametasona/uso terapéutico , Administración TópicaRESUMEN
PURPOSE: To perform a comparative analysis of visual, refractive, and tomographic outcomes of combined topography-guided photorefractive keratectomy (TG-PRK) and corneal crosslinking (CXL) in patients with progressive versus stable keratoconus. METHODS: Longitudinal retrospective case-control study. Patients with keratoconus submitted to simultaneous TG-PRK and CXL were included, with a minimum follow-up of 12 months up to 3 years. According to predefined disease progression criteria, patients were considered as progressive or stable. RESULTS: A total of 101 eyes from 93 patients were included, 62 considered progressive and 39 stable keratoconus. All baseline characteristics were similar between groups, except for age at surgery (progressive: 23.40 ± 4.22 years; stable: 35.97 ± 9.09; P < 0.001). Logarithm of the minimum angle of resolution CDVA improved significantly in progressive (baseline: 0.48 ± 0.24; 12 months: 0.33 ± 0.29; P < 0.001) and stable (baseline: 0.51 ± 0.24; 12 months: 0.28 ± 0.21; P < 0.001) patients, with no differences between groups. Maximum keratometry decreased significantly in progressive (baseline: 59.18 ± 5.63 diopters; 12 months: 54.73 ± 5.95; P < 0.001) and stable (baseline: 57.77 ± 5.02; 12 months: 53.59 ± 4.20; P < 0.001) patients, with no differences between groups. Index of surface variance significantly improved in progressive (baseline: 109.18 ± 31.74 diopters; 12 months: 94.11 ± 34.11; P < 0.001) and stable (baseline: 102.87 ± 29.52; 12 months: 86.95 ± 27.21; P < 0.001) patients, with no differences between groups. Other tomographic outcomes were also similar between groups. Pachymetry significantly decreased after surgery but remained stable throughout the follow-up. CONCLUSIONS: Combined TG-PRK and CXL is a safe and effective procedure for improving CDVA and regularizing the cornea, with comparable visual, refractive, and tomographic outcomes in both progressive and stable keratoconus. Combined TG-PRK and CXL may be added to the armamentarium of therapeutic tools for visual rehabilitation in patients with stable keratoconus.
RESUMEN
Variants in the retinitis pigmentosa GTPase regulator (RPGR) gene are responsible for the majority of X-linked retinitis pigmentosa cases, which not only affects male patients but also some heterozygous females. Vision-related disability and anxiety of patients with RPGR-associated retinal degeneration have never been explored before. This study aimed to evaluate self-reported visual function and vision-related anxiety in a Portuguese cohort of male and female patients with RPGR-associated retinal degeneration using two validated patient-reported outcome measures. Cross-sectional data of thirty-two genetically-tested patients was examined, including scores of the Michigan retinal degeneration questionnaire (MRDQ) and Michigan vision-related anxiety questionnaire. Patients were classified according to retinal phenotypes in males (M), females with male phenotype (FM), and females with radial or focal pattern. Both M and FM revealed higher rod-function and cone-function anxiety scores (p < 0.017). Most MRDQ disability scores were higher in M and FM (p < 0.004). Overall, positive correlations (p < 0.004) were found between every MRDQ domain and both anxiety scores. In RPGR-associated retinal degeneration, males and females with male phenotype show similar levels of increased vision-related anxiety and disability. Every MRDQ visual function domain showed a strong correlation with anxiety scores.
Asunto(s)
Ansiedad , Proteínas del Ojo , Degeneración Retiniana , Autoinforme , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Degeneración Retiniana/fisiopatología , Proteínas del Ojo/genética , Estudios Transversales , Retinitis Pigmentosa/fisiopatología , Retinitis Pigmentosa/psicología , Retinitis Pigmentosa/genética , Anciano , Fenotipo , Adulto Joven , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To assess the possible correlation between patients' personality traits and subjective perception of quality of vision (QoV), after multifocal intraocular lens (mIOL) implantation. METHODS: patients who had bilateral implantation of a non-diffractive X-WAVE or a trifocal lens were assessed 6 months postoperatively. Patients answered the NEO-Five Factor Inventory (NEO-FFI-20) questionnaire ("Big Five five-factor personality model") to examine their personality. Six months following surgery, patients were asked to fill a QoV questionnaire where they graded the frequency of 10 common visual symptoms. Primary outcomes were to evaluate the correlation between personality scores and the reported frequency of visual disturbances. RESULTS: The study comprised 20 patients submitted to bilateral cataract surgery, 10 with a non-diffractive X-WAVE lens (AcrySof® IQ Vivity) and 10 with a trifocal lens (AcrySof® IQ PanOptix). Mean age was 60.23 (7.06) years. Six months following surgery, patients with lower scores of conscientiousness and extroversion reported a higher frequency of visual disturbances (blurred vision, P = .015 and P = .009, seeing double images P = .018 and P = .006, and having difficulties focusing, P = .027 and P = .022, respectively). In addition, patients with high neuroticism scores had more difficulty focusing (P = .033). CONCLUSIONS: In this study, personality traits such as low conscientiousness and extroversion and high neuroticism significantly influenced QoV perception 6 months after bilateral multifocal lens implantation. Patients' personality questionnaires could be a useful preoperative assessment test to a mIOL.