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The association of early-onset non-progressive ataxia and miosis is an extremely rare phenotypic entity occasionally reported in the literature. To date, only one family (two siblings and their mother) has benefited from a genetic diagnosis by the identification of a missense heterozygous variant (p.Arg36Cys) in the ITPR1 gene. This gene encodes the inositol 1,4,5-trisphosphate receptor type 1, an intracellular channel that mediates calcium release from the endoplasmic reticulum. Deleterious variants in this gene are known to be associated with two types of spinocerebellar ataxia, SCA15 and SCA29, and with Gillespie syndrome that is associated with ataxia, partial iris hypoplasia, and intellectual disability. In this work, we describe a novel individual carrying a heterozygous missense variant (p.Arg36Pro) at the same position in the N-terminal suppressor domain of ITPR1 as the family previously reported, with the same phenotype associating early-onset non-progressive ataxia and miosis. This second report confirms the implication of ITPR1 in the miosis-ataxia syndrome and therefore broadens the clinical spectrum of the gene. Moreover, the high specificity of the phenotype makes it a recognizable syndrome of genetic origin.
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Receptores de Inositol 1,4,5-Trifosfato , Miosis , Femenino , Humanos , Ataxia/genética , Ataxia/patología , Heterocigoto , Receptores de Inositol 1,4,5-Trifosfato/genética , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Miosis/genética , Miosis/patología , Mutación Missense/genética , Linaje , Fenotipo , AncianoRESUMEN
BACKGROUND: Although ocular adverse events are frequent in AD patients treated with dupilumab, their characterization remains limited due to a lack of prospective studies with a systematic ophthalmological examination. OBJECTIVE: To examine the incidence, characteristics and risk factors of dupilumab-induced ocular adverse events. METHODS: A prospective, multicenter, and real-life study in adult AD patients treated with dupilumab. RESULTS: At baseline, 27 out of 181 patients (14.9%) had conjunctivitis. At week 16 (W16), 25 out of 27 had improved their conjunctivitis and 2 remained stable and 34 out of 181 patients (18.7%) had dupilumab-induced blepharoconjunctivitis: either de novo (n = 32) or worsening of underlying blepharoconjunctivitis (n = 2). Most events (27/34; 79.4%) were moderate. A multivariate analysis showed that head and neck AD (OR = 7.254; 95%CI [1.938-30.07]; p = 0.004), erythroderma (OR = 5.635; 95%CI [1.635-21.50]; p = 0.007) and the presence of dry eye syndrome at baseline (OR = 3.51; 95%CI [3.158-13.90]; p = 0.031) were independent factors associated with dupilumab-induced blepharoconjunctivitis. LIMITATIONS: Our follow-up period was 16 weeks and some late-onset time effects may still occur. CONCLUSION: This study showed that most dupilumab-induced blepharoconjunctivitis cases are de novo. AD severity and conjunctivitis at baseline were not found to be associated risk factors in this study.
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Conjuntivitis , Dermatitis Atópica , Adulto , Humanos , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/diagnóstico , Estudios Prospectivos , Anticuerpos Monoclonales Humanizados/efectos adversos , Conjuntivitis/inducido químicamente , Conjuntivitis/epidemiología , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
OBJECTIVES: To evaluate the success rate, efficacy, and safety of the ICD 16.5 mini-scleral gas permeable (GP) contact lens. METHODS: This prospective study included referred consecutive patients with irregular corneas and severe ocular surface disease (OSD) in treatment failure. All patients were fitted with the ICD 16.5 mini-scleral GP lens. Even though we had some limited experience with scleral lenses, it was our first experience with the ICD 16.5 mini-scleral GP lens. Efficacy was assessed by comparing best-corrected visual acuity (BCVA) with the mini-scleral lens to baseline BCVA. A subjective visual functioning questionnaire (comfort score, visual quality score, handling rating, and wearing time) was administered in a face-to-face structured interview. RESULTS: Thirty-nine eyes of 23 patients with a mean age of 43±16 years were included. Fitting indications were keratoconus (46%), post-penetrating keratoplasty (21%), other irregular astigmatism (15%), and severe OSD (18%). Twenty-five eyes (64%) were successfully fitted with an 18-month follow-up. The mini-scleral GP lens BCVA was 0.16 logarithm of the minimum angle of resolution (logMAR; 20/25) versus a baseline BCVA of 0.44 logMAR (20/63; P<0.001). Comfort and visual quality scores were 8.5/10 and 7.5/10, respectively. No complications were detected in 96% of the eyes (95% confidence interval, 76.1%-99.4%). One eye experienced corneal graft swelling. CONCLUSIONS: The present findings suggest that the ICD 16.5 mini-scleral GP lens is an effective and safe alternative for managing challenging corneas in a therapeutic impasse.
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Enfermedades de la Córnea/cirugía , Implantación de Lentes Intraoculares/métodos , Lentes Intraoculares , Esclerótica/cirugía , Agudeza Visual , Adolescente , Adulto , Anciano , Niño , Preescolar , Enfermedades de la Córnea/diagnóstico , Enfermedades de la Córnea/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Diseño de Prótesis , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To evaluate to what extent the modification of corneal asphericity to induce spherical aberration (SA) can improve the depth of focus and to determine whether preoperative adaptive optics assessment (Voptica SL) can predict an optimal SA value for each patient. DESIGN: Comparative, prospective clinical trial with paired eye control. PARTICIPANTS: Patients ≥45 years old who are hyperopic from +1.00 to +2.50 diopters (D), with eyes suitable for LASIK surgery. INTERVENTION: Bilateral hyperopic LASIK surgery using a 200-Hz Allegretto excimer laser. The dominant eye was operated using a conventional profile. The nondominant eye was programmed with an aspheric ablation profile and -0.75 D monovision. MAIN OUTCOME MEASURES: Primary outcome was the correlation between postoperative SA and depth of focus, defined as the pseudo-accommodation value (PAV = [1/reading distance {m}] - minimum addition [D]). Main secondary outcome was the comparison of depth of focus between patients with an induced SA close to the optimal one (group 1), patients with an induced SA far from the optimal one (group 2), and patients for whom SA induction did not increase the depth of focus (control group). RESULTS: We included 76 patients. Between preoperative and postoperative assessment, the mean increase of distance-corrected PAV for near vision was +0.25±0.64 D (P < 0.001) for dominant eyes and +0.63±0.55 D (P < 0.001) for nondominant eyes. As the level of negative or positive postoperative SA increased, PAV for intermediate and near vision increased. Among the 37 eyes that followed the preoperative adaptive optics assessment, the mean PAV increase at near was significantly higher (P < 0.05) in group 1 (0.93±0.50 D) than in group 2 (0.46±0.42 D) and than in the control group (0.35±0.32 D). The mean optimal SA value determined by the dynamic simulation procedure to optimize the depth of focus was -0.18±0.13 µm at 4.5 mm. CONCLUSIONS: Aspheric hyperopic LASIK can increase the depth of focus without impairing far vision, but this benefit would be maximal and reproducible if we could define and achieve an optimal SA value determined by preoperative assessment using an adaptive optics instrument.
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Aberración de Frente de Onda Corneal/fisiopatología , Percepción de Profundidad/fisiología , Hiperopía/cirugía , Queratomileusis por Láser In Situ/métodos , Láseres de Excímeros/uso terapéutico , Presbiopía/fisiopatología , Anciano , Predominio Ocular/fisiología , Femenino , Humanos , Hiperopía/fisiopatología , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Estudios Prospectivos , Agudeza Visual/fisiologíaRESUMEN
BACKGROUND: Corneal intraepithelial dyskeratosis is an extremely rare condition. The classical form, affecting Native American Haliwa-Saponi tribe members, is called hereditary benign intraepithelial dyskeratosis (HBID). Herein, we present a new form of corneal intraepithelial dyskeratosis for which we identified the causative gene by using deep sequencing technology. METHODS AND RESULTS: A seven member Caucasian French family with two corneal intraepithelial dyskeratosis affected individuals (6-year-old proband and his mother) was ascertained. The proband presented with bilateral complete corneal opacification and dyskeratosis. Palmoplantar hyperkeratosis and laryngeal dyskeratosis were associated with the phenotype. Histopathology studies of cornea and vocal cord biopsies showed dyskeratotic keratinisation. Quantitative PCR ruled out 4q35 duplication, classically described in HBID cases. Next generation sequencing with mean coverage of 50× using the Illumina Hi Seq and whole exome capture processing was performed. Sequence reads were aligned, and screened for single nucleotide variants and insertion/deletion calls. In-house pipeline filtering analyses and comparisons with available databases were performed. A novel missense mutation M77T was discovered for the gene NLRP1 which maps to chromosome 17p13.2. This was a de novo mutation in the proband's mother, following segregation in the family, and not found in 738 control DNA samples. NLRP1 expression was determined in adult corneal epithelium. The amino acid change was found to destabilise significantly the protein structure. CONCLUSIONS: We describe a new corneal intraepithelial dyskeratosis and how we identified its causative gene. The NLRP1 gene product is implicated in inflammation, autoimmune disorders, and caspase mediated apoptosis. NLRP1 polymorphisms are associated with various diseases.
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Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Reguladoras de la Apoptosis/genética , Disqueratosis Congénita/genética , Epitelio Corneal/patología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adulto , Proteínas Reguladoras de la Apoptosis/metabolismo , Niño , Queratocitos de la Córnea/patología , Disqueratosis Congénita/patología , Epitelio Corneal/metabolismo , Exoma , Femenino , Frecuencia de los Genes , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Mutación Missense , Proteínas NLR , Linaje , Polimorfismo de Nucleótido SimpleRESUMEN
PURPOSE: Corneal crosslinking (CXL) is the standard treatment of progressive keratoconus (KC). We evaluated the safety and 10-year outcomes of conventional "epithelial-off" CXL for progressive KC for the first time in a cohort in France. METHODS: We conducted a retrospective review of patients undergoing conventional CXL (Dresden protocol) in our tertiary ophthalmology department from 2006 to 2011 with 10-year follow-up. The primary outcome was change in preoperative versus postoperative keratometry measured by maximum keratometry (Kmax), steep keratometry (K2), flat keratometry (K1), mean keratometry (Km), and topographic cylinder. Secondary outcomes were changes in visual and refractive outcomes. We report postoperative complications and adverse events. RESULTS: Eighty-nine eyes from 76 patients (67% male patients, mean age 22.7 ± 7.6 years) were included. Mean Kmax (-2.31 ± 2.98 diopters (D); P < 0.00001), K2 (-2.07 ± 3.15 D; P < 0.00001), K1 (-1.00 ± 2.29 D; P = 0.00008), Km (-1.53 ± 2.47 D; P < 0.00001), and topographic cylinder (-1.15 ± 2.53 D; P = 0.00004) significantly decreased 10 years after CXL compared with preoperative baseline. Significant decreases were still observed between 5 and 10 years after for mean Kmax, mean K2, mean K1, and mean Km. Mean distance best spectacle-corrected visual acuity and mean manifest refraction spherical equivalent were significantly improved after 10 years versus before CXL. The 10-year rate of repeat CXL was n = 3/76 patients (4%) (all younger than 18 years at first CXL) and of loss of >3 lines in best spectacle-corrected visual acuity was n = 1/76 patients (1%). CONCLUSIONS: Progressive KC was effectively stabilized with a prolonged flattening and maintenance of functional vision improvements after 10 years. Repeat CXL was rare and only required among younger patients.
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Purpose: Multiple myeloma (MM) is the second most common neoplastic blood disease worldwide. Belantamab mafodotin is a new antibody conjugate anti-B-cell maturation antigen effective against refractory myelomas. It induces intracorneal microcysts leading to refractive fluctuations. The aim of this study is to assess the value of monitoring refractive fluctuations based on the location of microcystic-like epithelial changes (MECs) to facilitate patient follow-up. Methods: This observational and multicentric study was conducted using data collected from several French centers contacted through secure email through a standardized data collection table. Results: The fluctuation of objective refraction in spherical equivalent confirms a significant myopic shift from peripheral to central forms. A decrease in the best-corrected visual acuity (BCVA), an increase in keratometry, and an increase in central epithelial pachymetry have also been observed when MECs migrate toward the center. Conclusion: The myopization found in our study in patients with central and paracentral MECs is consistent with current literature. Fluctuations in BCVA, keratometry, and epithelial pachymetry are also consistent. This study is the first real-world study and highlights heterogeneity in follow-up, emphasizing the need to establish multidisciplinary follow-up strategies. The analysis of refractive fluctuations appears to be a reproducible and noninvasive screening method that could facilitate patient follow-up without the need for consultation focused on corneal diseases.
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Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious and rare diseases, most often drug-induced, and their incidence has been estimated at 6 cases/million/year in France. SJS and TEN belong to the same spectrum of disease known as epidermal necrolysis (EN). They are characterized by more or less extensive epidermal detachment, associated with mucous membrane involvement, and may be complicated during the acute phase by fatal multiorgan failure. SJS and TEN can lead to severe ophthalmologic sequelae. There are no recommendations for ocular management during the chronic phase. We conducted a national audit of current practice in the 11 sites of the French reference center for toxic bullous dermatoses and a review of the literature to establish therapeutic consensus guidelines. Ophthalmologists and dermatologists from the French reference center for epidermal necrolysis were asked to complete a questionnaire on management practices in the chronic phase of SJS/TEN. The survey focused on the presence of a referent ophthalmologist at the center, the use of local treatments (artificial tears, corticosteroid eye drops, antibiotic-corticosteroids, antiseptics, vitamin A ointment (VA), cyclosporine, tacrolimus), the management of trichiatic eyelashes, meibomian dysfunction, symblepharons, and corneal neovascularization, as well as the contactologic solutions implemented. Eleven ophthalmologists and 9 dermatologists from 9 of the 11 centers responded to the questionnaire. Based on questionnaire results, 10/11 ophthalmologists systematically prescribed preservative-free artificial tears, and 11/11 administered VA. Antiseptic or antibiotic eye drops or antibiotic-corticosteroid eye drops were recommended as needed by 8/11 and 7/11 ophthalmologists, respectively. In case of chronic inflammation, topical cyclosporine was consistently proposed by 11/11 ophthalmologists. The removal of trichiatic eyelashes was mainly performed by 10/11 ophthalmologists. Patients were referred to a reference center for fitting of scleral lenses (10/10,100%). Based on this practice audit and literature review, we propose an evaluation form to facilitate ophthalmic data collection in the chronic phase of EN and we also propose an algorithm for the ophthalmologic management of ocular sequelae.
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Síndrome de Stevens-Johnson , Humanos , Síndrome de Stevens-Johnson/complicaciones , Gotas Lubricantes para Ojos/uso terapéutico , Progresión de la Enfermedad , Ciclosporina/uso terapéutico , Corticoesteroides/uso terapéuticoRESUMEN
Among the new biological therapies for atopic diseases, dupilumab is a fully human monoclonal antibody directed against IL-4Rα, the common chain of interleukin-4 and interleukin-13 receptors. Dupilumab showed clinical improvements in patients with atopic dermatitis, asthma, and chronic rhinosinusitis and is currently under development for other indications. While dupilumab is considered to be well tolerated, a number of recent publications have reported various adverse events. This review aims to summarize the current knowledge about these adverse events, which may help clinicians to improve the follow-up of patients on dupilumab. Injection-site reactions are the most common reported adverse event. However, dupilumab has also been shown to cause ophthalmic complications (e.g., dry eyes, conjunctivitis, blepharitis, keratitis, and ocular pruritus), head and neck dermatitis, onset of psoriatic lesions, progression of cutaneous T-cell lymphoma exacerbation, alopecia areata, hypereosinophilia, and arthritis. Most are managed during dupilumab treatment continuation, but some (e.g., severe conjunctivitis) may result in a discontinuation of treatment. Their molecular origin is unclear and requires further investigations. Among other hypothesis, it has been suggested that T helper (Th)2-mediated pathway inhibition may worsen Th1/Th17-dependent immune responses. An ophthalmological examination for the presence of potential predictive indicators of ophthalmic adverse events is recommended before initiation of dupilumab therapy.
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Asma , Conjuntivitis , Dermatitis Atópica , Anticuerpos Monoclonales Humanizados/efectos adversos , Conjuntivitis/diagnóstico , Conjuntivitis/tratamiento farmacológico , Dermatitis Atópica/diagnóstico , HumanosRESUMEN
Keratoconus (KC) is a multifactorial progressive ectatic disorder characterized by local thinning of the cornea, leading to decreased visual acuity due to irregular astigmatism and opacities. Despite the evolution of advanced imaging methods, the exact etiology of KC remains unknown. Our aim was to investigate the involvement of corneal epithelium in the pathophysiology of the disease. Corneal epithelial samples were collected from 23 controls and from 2 cohorts of patients with KC: 22 undergoing corneal crosslinking (early KC) and 6 patients before penetrating keratoplasty (advanced KC). The expression of genes involved in the epidermal terminal differentiation program and of the oxidative stress pathway was assessed by real time PCR analysis. Presence of some of the differentially expressed transcripts was confirmed at protein level using immunofluorescence on controls and advanced KC additional corneal samples. We found statistically significant under-expression in early KC samples of some genes known to be involved in the mechanical resistance of the epidermis (KRT16, KRT14, SPRR1A, SPRR2A, SPRR3, TGM1 and TGM5) and in oxidative stress pathways (NRF2, HMOX1 and HMOX2), as compared to controls. In advanced KC samples, expression of SPRR2A and HMOX1 was reduced. Decreased expression of keratin (KRT)16 and KRT14 proteins was observed. Moreover, differential localization was noted for involucrin, another protein involved in the epidermis mechanical properties. Finally, we observed an immunofluorescence staining for the active form of NRF2 in control epithelia that was reduced in KC epithelia. These results suggest a defect in the mechanical resistance and the oxidative stress defense possibly mediated via the NRF2 pathway in the corneal keratoconic epithelium.
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Epitelio Corneal , Queratocono , Córnea/metabolismo , Proteínas Ricas en Prolina del Estrato Córneo/metabolismo , Epitelio Corneal/metabolismo , Humanos , Queratinas/metabolismo , Queratocono/genética , Queratocono/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/genéticaRESUMEN
PURPOSE: To evaluate the efficacy and safety of transepithelial corneal cross-linking (CXL) with supplemental oxygen. METHODS: This was a prospective, non-comparative, pilot cohort study conducted at the National Reference Center for Keratoconus (Toulouse, France) on patients with progressive keratoconus. Transepithelial, pulsed, accelerated CXL was performed in an oxygen-rich atmosphere. Oxygen goggles were applied to the eyes to maintain a high level of oxygen during treatment. The main efficacy outcome was the mean change from baseline in maximum keratometry (Kmax) and the secondary outcomes were the mean changes in flat keratometry (K1), steep keratometry (K2), mean keratometry (Km), corrected distance visual acuity (CDVA), uncorrected distance visual acuity (UDVA), and demarcation line depth. The safety outcomes were the incidence of adverse events, the mean change in pachymetry, and endothelial cell count. RESULTS: Thirty-four eyes of 34 patients were included. At 12 months postoperatively, the Kmax decreased by 1.56 ± 1.71 diopters (D) (P < .0001) and CDVA improved by 0.093 ± 0.193 logMAR (P < .02). The K2 and Km decreased by 0.51 ± 1.03 D (P < .02) and 0.40 ± 0.78 D (P < .01), respectively. There was no change in K1 and UDVA. The most frequent adverse event was corneal haze (64.78%). There were neither cases of infectious keratitis or loss of more than two lines in CDVA nor changes in pachymetry or endothelial cell count. CONCLUSIONS: Transepithelial CXL performed in an oxygen-rich atmosphere results in improved Kmax and CDVA with good safety. These promising findings suggest that this procedure could be safe and capable of halting the progression of keratoconus. [J Refract Surg. 2021;37(1):42-48.].
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Queratocono , Fotoquimioterapia , Colágeno/uso terapéutico , Paquimetría Corneal , Topografía de la Córnea , Reactivos de Enlaces Cruzados/uso terapéutico , Humanos , Queratocono/tratamiento farmacológico , Oxígeno , Fármacos Fotosensibilizantes/uso terapéutico , Proyectos Piloto , Estudios Prospectivos , Riboflavina/uso terapéutico , Rayos UltravioletaRESUMEN
PURPOSE: To compare the outcomes of transepithelial photorefractive intrastromal corneal crosslinking (CXL) and photorefractive keratectomy (PRK) in eyes with low myopia. SETTING: Purpan Hospital, Toulouse, France. DESIGN: Prospective case series. METHODS: Myopic patients with a manifest refraction spherical equivalent (MRSE) of -1.00 to -2.50 diopters (D) and a cylindrical component of plano to -0.75 D were included. The dominant eye had PRK (PRK eyes). The nondominant eye had transepithelial photorefractive intrastromal CXL with riboflavin (ParaCel Part 1 and 2), 30 mW/cm2 pulsed ultraviolet-A irradiation centered on the pupil (Mosaic System) for 16 minutes and 40 seconds, and a supplemental oxygen delivery mask (CXL eyes). The primary outcome measure was the change in the MRSE. Other outcome measures were the uncorrected (UDVA) and corrected (CDVA) distance visual acuities, mean keratometry, and endothelial cell count (ECC) over a 6-month follow-up. Adverse events were assessed. RESULTS: Nineteen patients were included. By 6 months, the mean MRSE had decreased by 0.72 D ± 0.42 (SD) in CXL eyes and by 1.35 ± 0.46 D in PRK eyes (P < .001). The mean change in UDVA was -0.35 ± 0.21 logarithm of the minimum angle of resolution (logMAR) in CXL eyes and -0.66 ± 0.19 logMAR in PRK eyes (P < .001). No complications were reported. The change in the ECC and CDVA was not statistically significant. CONCLUSIONS: Photorefractive keratectomy provided better visual and refractive outcomes than transepithelial photorefractive intrastromal CXL. Transepithelial photorefractive intrastromal CXL, however, showed the potential refractive effect of CXL but with a limited magnitude of myopic correction.
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Reactivos de Enlaces Cruzados/uso terapéutico , Epitelio Corneal/cirugía , Miopía/terapia , Fotoquimioterapia/métodos , Queratectomía Fotorrefractiva/métodos , Refracción Ocular/fisiología , Riboflavina/uso terapéutico , Adulto , Sustancia Propia , Topografía de la Córnea , Femenino , Estudios de Seguimiento , Humanos , Masculino , Miopía/patología , Fármacos Fotosensibilizantes/uso terapéutico , Proyectos Piloto , Estudios Prospectivos , Agudeza VisualRESUMEN
PURPOSE: To describe the surgical technique and report the outcomes of 2 patients treated with femtosecond laser-assisted ipsilateral rotational lamellar autokeratoplasty in central corneal scars. METHODS: The corneal scar depth was mapped using preoperative optical coherence tomography. An eccentric lamellar lenticule was cut with a femtosecond laser and rotated to decenter corneal opacity and free the pupil area in 2 patients with nonprogressive central corneal scars. The surgical plan was set after simulating lenticule rotation with a digital corneal image and computer software. RESULTS: In both cases, the corneal scar was decentered inferiorly, out of the pupillary area, with increased postoperative visual acuity but visual outcome limitations secondary to corneal irregularities and residual deep opacity. CONCLUSIONS: Femtosecond laser-assisted ipsilateral rotational lamellar autokeratoplasty is effective for shifting central corneal opacities and can be considered in appropriate cases.
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Opacidad de la Córnea/cirugía , Queratoplastia Penetrante/métodos , Láseres de Excímeros/uso terapéutico , Cicatriz/cirugía , Femenino , Humanos , Masculino , Proyectos Piloto , Estudios Prospectivos , Adulto JovenRESUMEN
PURPOSE: To evaluate the efficacy and safety of the combined implantation of a monofocal intraocular lens (IOL) in the capsular bag with a diffractive multifocal IOL designed for sulcus placement (Reverso). SETTING: Purpan Hospital, Toulouse, and Helios Clinic, Saint-Jean-de-Luz, France. DESIGN: Prospective case series. METHODS: The multifocal IOL piggyback IOL was implanted in the sulcus during cataract surgery. Visual acuity, defocus curve, contrast sensitivity, IOL positioning, and patient satisfaction were assessed with 1-year follow-ups. RESULTS: Fifty-four eyes of 27 patients were included. At 1-month, monocular uncorrected distance (UDVA) and near (UNVA) visual acuities were 0.13 logarithm of the minimum angle of resolution (logMAR) ± 0.18 (SD) and 0.20 ± 0.16 logMAR, respectively. Binocular UDVA and UNVA were 0.03 ± 0.06 and 0.12 ± 0.08 logMAR, respectively. At 1 year, the mean monocular logMAR UDVA, corrected distance visual acuity, UNVA, and corrected near visual acuity were 0.10 ± 0.11, 0.02 ± 0.06, 0.18 ± 0.12, and 0.13 ± 0.08, respectively. The defocus curve and contrast sensitivity values were comparable to those obtained with other multifocal IOLs. On Scheimpflug imaging, the mean distance between the sulcus multifocal IOL and the monofocal IOL was 517 ± 141 µm. At 1 year, ultrasound biomicroscopy showed an annular fibrosis of the anterior capsule in 94.4% of the eyes. Complications included 1 posttraumatic IOL decentration and 1 slight corectopia. Eighty-nine percent of patients reported satisfaction. CONCLUSIONS: The piggyback implantation of this multifocal IOL seemed to be safe and effective. It might provide similar results as a primary in-the-bag multifocal IOL, with the advantage of reversibility that might extend primary or secondary implantation.
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Implantación de Lentes Intraoculares/métodos , Lentes Intraoculares Multifocales , Facoemulsificación/métodos , Seudofaquia/cirugía , Anciano , Anciano de 80 o más Años , Cámara Anterior/diagnóstico por imagen , Recuento de Células , Sensibilidad de Contraste/fisiología , Endotelio Corneal/citología , Femenino , Humanos , Presión Intraocular/fisiología , Masculino , Microscopía Acústica , Persona de Mediana Edad , Satisfacción del Paciente , Estudios Prospectivos , Seudofaquia/fisiopatología , Encuestas y Cuestionarios , Tomografía de Coherencia Óptica , Agudeza Visual/fisiologíaRESUMEN
PURPOSE: To compare the efficacy and safety of topography-guided corneal collagen cross-linking (TG-CXL) to conventional corneal CXL (C-CXL) in progressive keratoconus. METHODS: In this prospective, nonrandomized clinical trial, 60 eyes of 60 patients were scheduled to receive either TG-CXL (30 eyes with deepithelialization focused on the cone, riboflavin application for 10 minutes, and 30 mW/cm2 pulsed ultraviolet-A irradiance pattern according to topography) or C-CXL (30 eyes treated in accordance with the Dresden protocol). Patients were observed for 1 year postoperatively. Maximum keratometry (Kmax), mean keratometry in the inferior part of the cornea (I index), corrected distance visual acuity (CDVA), demarcation line observed in optical coherence tomography, and nerves and cell densities analyzed by confocal microscopy were compared preoperatively and at 1 year postoperatively. RESULTS: The difference was significant for both Kmax (P < .01) and I index (P < .01) between the two groups. CDVA improved significantly in the TG-CXL (0.2162 ± 0.2495 logMAR, P < .05) versus the C-CXL (0.2648 ± 0.2574 logMAR, P = .104) group. A stromal demarcation line was observed in both treatment groups, with similar depth at the top of the cone (P = .391), but it was shallower at the surrounding area in the TG-CXL group (P < .0001). Stromal evaluation by confocal microscopy showed less damage and faster healing in the surrounding area than on the cone area in the TG-CXL group. CONCLUSIONS: At 1 year postoperatively, TG-CXL seems to be as safe as C-CXL with stronger flattening in Kmax and I index and better improvement in CDVA. TG-CXL induces a biological gradient between the cone and the surrounding area that facilitates nerve and cell recovery. [J Refract Surg. 2017;33(5):290-297.].
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Colágeno/farmacología , Sustancia Propia/patología , Reactivos de Enlaces Cruzados/farmacología , Queratocono/tratamiento farmacológico , Fotoquimioterapia/métodos , Riboflavina/farmacología , Agudeza Visual , Paquimetría Corneal , Topografía de la Córnea , Femenino , Estudios de Seguimiento , Humanos , Queratocono/diagnóstico , Masculino , Microscopía Confocal , Fármacos Fotosensibilizantes/farmacología , Estudios Prospectivos , Tomografía de Coherencia Óptica , Rayos Ultravioleta , Adulto JovenRESUMEN
PURPOSE: We compared an iontophoresis riboflavin delivery technique for transepithelial corneal collagen crosslinking (I-CXL) with a conventional CXL (C-CXL). METHODS: We designed three experimental sets using 152 New Zealand rabbits to study riboflavin application by iontophoresis using charged riboflavin solution (Ricrolin+) with a 1-mA current for 5 minutes. The first set was to compare riboflavin concentration measured by HPLC in corneas after iontophoresis or conventional riboflavin application. The second set was to analyze autofluorescence and stromal collagen modification immediately and 14 days after I-CXL or C-CXL, by using nonlinear two-photon microscopy (TP) and second harmonic generation (SHG). In the third set, physical modifications after I-CXL and C-CXL were evaluated by stress-strain measurements and by studying corneal resistance against collagenase digestion. RESULTS: Based on HPLC analysis, we found that iontophoresis allowed riboflavin diffusion with 2-fold less riboflavin concentration than conventional application (936.2 ± 312.5 and 1708 ± 908.3 ng/mL, respectively, P < 0.05). Corneal TP and SHG imaging revealed that I-CXL and C-CXL resulted in a comparable increased anterior and median stromal autofluorescence and collagen packing. The stress at 10% strain showed a similar stiffness of corneas treated by I-CXL or C-CXL (631.9 ± 241.5 and 680.3 ± 216.4 kPa, respectively, P = 0.908). Moreover, we observed an increased resistance against corneal collagenase digestion after I-CXL and C-CXL (61.90% ± 5.28% and 72.21% ± 4.32% of remaining surface, respectively, P = 0.154). CONCLUSIONS: This experimental study suggests that I-CXL is a promising alternative methodology for riboflavin delivery in crosslinking treatments, preserving the epithelium.
Asunto(s)
Colágeno/administración & dosificación , Iontoforesis/métodos , Queratocono/tratamiento farmacológico , Riboflavina/administración & dosificación , Animales , Reactivos de Enlaces Cruzados , Modelos Animales de Enfermedad , Epitelio Corneal , Femenino , Queratocono/metabolismo , Queratocono/patología , Conejos , Riboflavina/farmacocinética , Complejo Vitamínico B/administración & dosificación , Complejo Vitamínico B/farmacocinéticaRESUMEN
PURPOSE: To characterize the expression of the bone morphogenetic protein-1 (BMP-1)/tolloid-like proteinases (collectively called BTPs), which include BMP-1, mammalian tolloid (mTLD), and mammalian tolloid-like 1 (mTLL-1) and 2 (mTLL-2), as well as the associated proteins procollagen C-proteinase enhancers (PCPE-1 and -2), in corneal scarring. METHODS: Using a mouse full-thickness corneal excision model, wound healing was followed for up to 28 days by transmission electron microscopy, immunohistology (BMP-1/mTLD and PCPE-1), and quantitative PCR (Q-PCR: collagen III, BMP-1/mTLD, mTLL-1, mTLL-2, PCPE-1, PCPE-2). Bone morphogenetic protein-1/mTLD and PCPE-1 were also immunolocalized in cases of human corneal scarring following injuries. RESULTS: In the mouse model, throughout the follow-up period, there was a large increase in collagen III mRNA expression in the stroma. By transmission electron microscopy, there was marked cellular infiltration into the wound as well as disorganization of collagen fibrils, but no significant difference in fibril diameter. In control corneas, by Q-PCR, BMP-1/mTLD showed the highest expression, compared to low levels of mTLL-1 and undetectable levels of mTLL-2, in both epithelium and stroma. Following wounding, both BMP-1/mTLD and PCPE-1 mRNA and protein increased, while PCPE-2 mRNA decreased. Finally, by immunofluorescence, BMP-1/mTLD and PCPE-1 were strongly expressed in the scar region in both mouse and human corneas. CONCLUSIONS: Bone morphogenetic protein-1/mTLD and PCPE-1 are upregulated in corneal scars. Both proteins may therefore contribute to the process of corneal scarring.