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PURPOSE: To assess ophthalmology residents satisfaction regarding surgical training during residency in France. METHODS: A questionnaire consisting of 28 questions was designed and sent to residents of ophthalmology across the 27 French regions. RESULTS: A total of 30.3% ophthalmology residents in France completed our questionnaire. All French regions participated. They rated 5,27 ± 2.42/10 the global surgical training during residency. They had performed at least one step of any type of ocular surgery for 93.4% of them, while 80.7% had completed at least one full cataract surgery, by the beginning of their second year of residency on average (Paris: 2.59 ± 1.36 semesters; regions: 4.05 ± 1.96 semesters, p < 0.0001). Only 48.9% identified a surgical mentor during their residency, but 82.2% did not clearly identify surgical goals & objectives during their training. Simulation was available for any type of ocular surgery to all residents in the Paris (Île-de-France) region and to 78.1% in other regions (p < 0.005). Residents who accessed drylabs and wetlabs gave a satisfaction score of 7.31 ± 1.89/10 and 6.39 ± 2.15/10 to it respectively. Simulation was a mandatory part of the curriculum for 35.2% of the resident. They commented on on reduced access to subspecialized surgery. They were willing for more access to simulation and surgery on real patients, as well for closer mentoring and clearly defined surgical goals within the curriculum. CONCLUSION: Ophthalmology residents seemed globally satisfied with their surgical training nationwide, although we observed disparities across region. They largely acknowledged a lack of standard procedures nationwide. They acclaimed simulation during the initial phase of residency, progressively switching towards surgery on real patients. An "operating license" during residency could be a viable way for the resident to demonstrate that they have acquired enough surgical abilities to perform surgery on real patients.
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Extração de Catarata , Internato e Residência , Oftalmologia , Cirurgiões , Humanos , Extração de Catarata/educação , Currículo , Oftalmologia/educação , Inquéritos e Questionários , Competência ClínicaRESUMO
Purpose: To investigate systemic and ocular toll-like receptor (TLR)-4 expression and its association with oxidative stress markers in ocular rosacea (OR). Methods: This prospective study included 40 patients with rosacea with ocular involvement and 20 healthy volunteers. Tear break-up time (TBUT), Schirmer test, meibomoscore, and ocular surface disease index (OSDI) scores were estimated for all participants. TLR-4 expression in conjunctival epithelium and peripheral blood mononuclear cells was quantified using real-time polymerase chain reaction (RT-PCR). In the tears and serum samples of all participants, antioxidant status (TAS), total oxidant status (TOS), and arylesterase (ARE) activation levels were measured using a fully automated spectrophotometric method, and the oxidative stress index (OSI) was calculated. Results: TLR-4 expression levels and oxidative stress status (TOS and OSI values) were significantly higher (p < 0.01), and antioxidant status (TAS and ARE values) were significantly lower (p < 0.01) in both ocular and blood samples of patients with OR compared with those in controls. A significant positive correlation was found between the ocular and blood values in all parameters (p < 0.05). According to the clinical associations of these results, we found negative correlations between TLR-4, OSI, and TBUT and between TLR-4 and Schirmer, whereas a positive correlation was observed between TLR-4, OSI, and meiboscore and between TLR-4, OSI, and OSDI (p < 0.05). No correlation was found between the OSI and Schirmer results (p = 0.92). Conclusions: TLR-4 and oxidative stress both play important roles in OR pathophysiology and are closely related to clinical findings.
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Antioxidantes , Rosácea , Humanos , Leucócitos Mononucleares/metabolismo , Oxidantes , Estresse Oxidativo/fisiologia , Estudos Prospectivos , Rosácea/genética , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismoRESUMO
Limbal epithelial stem/progenitor cells (LSCs) are adult stem cells located at the limbus, tightly regulated by their close microenvironment. It has been shown that Wnt signaling pathway is crucial for LSCs regulation. Previous differential gene profiling studies confirmed the preferential expression of specific Wnt ligands (WNT2, WNT6, WNT11, WNT16) and Wnt inhibitors (DKK1, SFRP5, WIF1, FRZB) in the limbal region compared to the cornea. Among all frizzled receptors, frizzled7 (Fzd7) was found to be preferentially expressed in the basal limbal epithelium. However, the exact localization of Wnt signaling molecules-producing cells in the limbus remains unknown. The current study aims to evaluate the in situ spatial expression of these 4 Wnt ligands, 4 Wnt inhibitors, and Fzd7. Wnt ligands, DKK1, and Fzd7 expression were scattered within the limbal epithelium, at a higher abundance in the basal layer than the superficial layer. SFRP5 expression was diffuse among the limbal epithelium, whereas WIF1 and FRZB expression was clustered at the basal limbal epithelial layer corresponding to the areas of high levels of Fzd7 expression. Quantitation of the fluorescence intensity showed that all 4 Wnt ligands, 3 Wnt inhibitors (WIF1, DKK1, FRZB), and Fzd7 were highly expressed at the basal layer of the limbus, then in a decreasing gradient toward the superficial layer (P < 0.05). The expression levels of all 4 Wnt ligands, FRZB, and Fzd7 in the basal epithelial layer were higher in the limbus than the central cornea (P < 0.05). All 4 Wnt ligands, 4 Wnt inhibitors, and Fzd7 were also highly expressed in the limbal stroma immediately below the epithelium but not in the corneal stroma (P < 0.05). In addition, Fzd7 had a preferential expression in the superior limbus compared to other limbal quadrants (P < 0.05). Taken together, the unique expression patterns of the Wnt molecules in the limbus suggests the involvement of both paracrine and autocrine effects in LSCs regulation, and a fine balance between Wnt activators and inhibitors to govern LSC fate.
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Epitélio Corneano , Limbo da Córnea , Adulto , Humanos , Via de Sinalização Wnt/fisiologia , Epitélio Corneano/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Limbo da Córnea/metabolismo , Córnea/fisiologiaRESUMO
Rosacea is a chronic inflammatory disease that affects the face skin. It is clinically classified into the following four subgroups depending on its location and severity: erythematotelangiectatic, papulopustular, phymatous, and ocular. Rosacea is a multifactorial disease triggered by favoring factors, the pathogenesis of which remains imperfectly understood. Recognized mechanisms include the innate immune system, with the implication of Toll-like receptors (TLRs) and cathelicidins; neurovascular deregulation involving vascular endothelial growth factor (VEGF), transient receptor potential (TRP) ion channels, and neuropeptides; and dysfunction of skin sebaceous glands and ocular meibomian glands. Microorganisms, genetic predisposition, corticosteroid treatment, and ultraviolet B (UVB) radiation are favoring factors. In this paper, we review the common and specific molecular mechanisms involved in the pathogenesis of cutaneous and ocular rosacea and discuss laboratory and clinical studies, as well as experimental models.
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Oftalmopatias/fisiopatologia , Modelos Biológicos , Rosácea/fisiopatologia , Dermatopatias/fisiopatologia , Animais , Modelos Animais de Doenças , Oftalmopatias/etiologia , Oftalmopatias/imunologia , Humanos , Rosácea/etiologia , Rosácea/imunologia , Dermatopatias/etiologia , Dermatopatias/imunologiaRESUMO
PURPOSE: To identify the incidence of, risk factors for, and outcomes of posterior segment complications (PSC) after Boston Type 1 keratoprosthesis (KPro) implantation. METHODS: Retrospective, consecutive case series of KPro procedures at the Stein Eye Institute. Data regarding ocular history, intraoperative details, postoperative management, and outcomes were collected. Eyes with at least one PSC (PSC group) were compared with eyes without PSC (No PSC group), and risk factors for PSC were determined. RESULTS: Ninety-five PSC occurred in 69/169 eyes (40.8%), at a mean of 20.1 months after KPro implantation (0.01 complications/eye month). The median follow-up after KPro implantation was 44.0 months (range 3.0-174.4). The most common PSC were epiretinal membrane (16.6%), cystoid macular edema (12.4%), vitritis (11.2%), and retinal detachment (9.5%). Previous retinal detachment repair, concomitant intraocular lens removal, postoperative aphakia, and vitritis were risk factors for retinal detachment. Postoperative infectious keratitis was a risk factor for epiretinal membrane, cystoid macular edema, and vitritis. The posterior segment complication group had a significantly higher rate of eyes failing to maintain visual acuity ≥20/200 (HR = 2.28; 95% CI = 1.35-3.85) and KPro retention failure rate (HR = 1.66; 95% CI = 0.95-2.91). CONCLUSION: Posterior segment complications occur in approximately 40% of eyes after KPro implantation, resulting in reduced visual outcomes and KPro retention.
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Órgãos Artificiais , Córnea , Segmento Posterior do Olho/patologia , Complicações Pós-Operatórias , Próteses e Implantes/efeitos adversos , Doenças Retinianas/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Implantação de Prótese , Doenças Retinianas/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Acuidade Visual/fisiologiaRESUMO
PURPOSE: To evaluate vision-related quality of life in keratoconus patients and associated impact of keratoconus severity indicators using the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). METHODS: This was a prospective cross-sectional study carried out from November 1, 2014, to April 30, 2015, in the corneal service of the Hôtel-Dieu hospital, Paris, France. A hundred and one keratoconus patients were consecutively enrolled. Participants completed a French-validated version of the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). Manifest refraction, maximum keratometry value, and corneal thinnest point were recorded. Associations between clinical and demographic factors, previous medical or surgical treatment, and NEI-VFQ-25 scale scores were evaluated. RESULTS: Vision-related quality of life was no better in patients managed with rigid gas permeable contact lens, collagen cross-linking, or intracorneal ring segment implantation, compared with untreated patients. In advanced keratoconus (stages II, III, and IV of Amsler-Krumeich classification), rigid gas permeable contact lens wearers had better general vision but more ocular pain. Distance-corrected visual acuity worse than 20/40, mean refractive cylinder > 2.5 diopters, and corneal thinnest point < 460 µm in the better eye were associated with a lower vision-related quality of life. In multivariate analysis, only the uncorrected and distance-corrected visual acuity of the better eye remained significantly correlated with vision-related quality of life. CONCLUSIONS: Low distance-corrected visual acuity in the better eye was the strongest predictor of low vision-related quality of life.
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Córnea/cirurgia , Ceratocone/psicologia , Qualidade de Vida , Acuidade Visual , Adolescente , Adulto , Córnea/patologia , Topografia da Córnea/métodos , Estudos Transversais , Feminino , Seguimentos , Humanos , Ceratocone/diagnóstico , Ceratocone/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Anterior segment optical coherence tomography (AS OCT) is a helpful tool used to diagnose and manage many corneal conditions, but its use has not been reported in case of peripheral ulcerative keratitis (PUK). The aim of this study is to describe AS OCT findings in cases of PUK. METHODS: Retrospective observational case series of six eyes presenting with a PUK and proven systemic vasculitis. Clinical course, slit lamp photographs, and AS OCT findings were the main outcomes. RESULTS: The AS OCT findings were found to correlate with the ocular disease's level of activity. In the acute stage, an absence of corneal epithelium, a scrambled appearance of the anterior stroma and a heterogeneous stromal reflectivity were observed. During the reduction of disease level activity, an irregular hyporeflective epithelium, a smoother anterior stroma, and a homogenous hyperreflective stroma were seen. At the healed stage, a filling of the corneal defect by a hyporeflective thick epithelium, the persistence of the hyperreflective underlying stroma, and a demarcation line were observed. The mean total corneal thickness at last follow-up was significantly thicker (509 ± 147 µm) compared with the mean corneal thickness at onset (408 ± 131 µm; P = 0.03). CONCLUSIONS: AS OCT provides an assessment of structural changes occurring in PUK, useful for its diagnosis and monitoring.
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Segmento Anterior do Olho/diagnóstico por imagem , Substância Própria/diagnóstico por imagem , Úlcera da Córnea/diagnóstico por imagem , Epitélio Corneano/diagnóstico por imagem , Tomografia de Coerência Óptica , Adulto , Idoso , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Substância Própria/patologia , Úlcera da Córnea/tratamento farmacológico , Quimioterapia Combinada , Epitélio Corneano/patologia , Feminino , Seguimentos , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos , Microscopia com Lâmpada de FendaAssuntos
Traumatismos Faciais/diagnóstico por imagem , Ferimentos por Arma de Fogo/complicações , Algoritmos , Traumatismos Oculares/diagnóstico por imagem , Traumatismos Oculares/etiologia , Traumatismos Oculares/mortalidade , Traumatismos Faciais/etiologia , Traumatismos Faciais/mortalidade , França , Humanos , Guias de Prática Clínica como Assunto , Tumultos , Borracha/efeitos adversos , Ferimentos por Arma de Fogo/mortalidadeAssuntos
Ferimentos Oculares Penetrantes/etiologia , Armas/classificação , Ferimentos e Lesões/etiologia , Adolescente , Adulto , Ferimentos Oculares Penetrantes/epidemiologia , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Armas/estatística & dados numéricos , Ferimentos e Lesões/diagnóstico por imagem , Ferimentos e Lesões/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Tumor necrosis factor-alpha inhibitors are widely used agents in the treatment of immune disorders such as rheumatoid arthritis and inflammatory bowel disease. Despite their anti-inflammatory action, paradoxical drug-induced inflammatory events have been occasionally associated with the use of infliximab, etanercept, and in a lesser extent adalimumab. However, eye involvement is uncommon and anterior uveitis is the only reported ocular adverse manifestation. It can be induced by etanercept, but has also been described during adalimumab therapy. We present here the first report of recurrent peripheral corneal infiltrates following subcutaneous injections of adalimumab. CASE PRESENTATION: A 34 year-old Caucasian woman with Crohn's disease presented to the emergency department with bilateral red eyes and discomfort 36 hours after she received her bimonthly dose of subcutaneous adalimumab. Examination revealed bilateral peripheral corneal infiltrates with characteristic features of immune infiltrates. Symptoms and infiltrates regressed after topical corticosteroid therapy, but recurred after each adalimumab injection over the following weeks. CONCLUSION: Paradoxical immune reactions associated with tumor necrosis factor-alpha inhibitors may result either from hypersensitivity mechanisms, or from immune-complex deposition via anti-adalimumab antibodies. Both mechanisms could explain this newly described manifestation. Care should be taken to search for corneal infiltrates in the event of red eye symptoms during adalimumab therapy since they respond to topical corticosteroids and do not necessarily prompt the discontinuation of the immunosuppressive therapy.
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Adalimumab/efeitos adversos , Anti-Inflamatórios/efeitos adversos , Doenças da Córnea/induzido quimicamente , Administração Tópica , Adulto , Doenças da Córnea/diagnóstico , Doenças da Córnea/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Dexametasona/uso terapêutico , Substituição de Medicamentos , Feminino , Glucocorticoides/uso terapêutico , Humanos , Injeções Subcutâneas , Soluções Oftálmicas , Pregnadienos/uso terapêutico , Recidiva , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
BACKGROUND: To compare the choroidal thickness (CT) and choroidal vascularity index (CVI) values in ocular rosacea (OR) patients across skin subtypes of the disease and healthy controls. METHODS: This prospective study included 90 eyes of 90 mild-moderate OR patients with different skin subtypes (30 phymatous, 30 papulopustular and 30 erythematotelangiectatic) and 30 eyes of 30 age-gender matched healthy volunteers. After obtaining the enhanced depth imaging optical coherence tomography images, the CT was measured at subfoveal, 1500µm nasal and 1500µm temporal to the fovea, and the CVI was calculated using Image J software in the subfoveal, nasal and temporal areas. RESULTS: There was no CT significant difference between OR patients and healthy controls in all regions (p>0.05). CVI values of OR patients were found to be significantly lower in the subfoveal, nasal and temporal regions compared to healthy controls (p=0.02, p=0.01, p=0.01, respectively). No CT difference was detected between the subtypes and healthy controls in all regions (p>0.05). Subfoveal-CVI was significantly lower in the phymatous subtype than the other subtypes and controls (p<0.05), while nasal and temporal-CVI were significantly lower in the phymatous and papulopustular subtypes than the erythematotelangiectatic subtype and controls. CONCLUSION: Our study demonstrated no difference between rosacea skin types and healthy controls in terms of CT. Phymatous and papulopustular subtypes were more likely to be affected by chronic inflammation with having lower CVI in most of the regions. Further studies are needed to investigate the association of inflammatory factors with CVI in OR.
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PURPOSE: To describe the incidence, timing, visual significance, and management of posterior segment complications after Boston type I keratoprosthesis implantation. METHODS: A retrospective chart review was conducted of all consecutive Boston type I keratoprostheses implanted by a single surgeon at a single institution over a 6-year period. Preoperative demographics, postoperative complications, and postoperative visual acuity outcomes were analyzed. RESULTS: One hundred and ten keratoprostheses were implanted in 98 eyes of 94 patients during the period under review. A minimum of 6-month follow-up was available for 83 eyes, with a mean follow-up of 28.2 months (range 6-84 months, median 23.7 months). The mean time to occurrence of any posterior segment complication was 5.6 months (range 0-42.1 months, median 5.2 months, n = 38). After keratoprosthesis surgery, 63% of all eyes had corrected distance visual acuity of 20/200 or better at last follow-up compared with 10% of eyes preoperatively. Thirty-eight eyes (40.9%) experienced at least 1 postoperative posterior segment complication, the most common of which were retinal detachment (16.9%, 14 of 83), choroidal detachment (16.9%, 14 of 83), and sterile vitritis (14.5%, 12 of 83). Corrected distance visual acuity was worse among eyes that experienced posterior segment complications compared with eyes that did not at multiple postoperative follow-up intervals (statistically significant up to 3 years) and at last follow-up (logarithm of the minimum angle of resolution ± SD = 1.45 ± 0.78 vs. 0.89 ± 0.81, P = 0.003). CONCLUSION: Posterior segment complications occur in a significant percentage of patients after keratoprosthesis surgery, resulting in a persistent reduction of visual acuity in a significant proportion of the affected eyes (corrected distance visual acuity ≤ 20/400 in 61% with complications vs. 24% without complications at last follow-up). Given this, and the anatomic difficulties associated with management of posterior segment complications after keratoprosthesis implantation, it is of particular importance to prevent posterior segment complications, whenever possible, in keratoprosthesis patients.
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Doenças da Coroide/etiologia , Doenças da Córnea/cirurgia , Transplante de Córnea , Complicações Pós-Operatórias , Próteses e Implantes , Descolamento Retiniano/etiologia , Corpo Vítreo/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças da Coroide/diagnóstico , Feminino , Seguimentos , Humanos , Incidência , Complicações Intraoperatórias , Masculino , Pessoa de Meia-Idade , Reoperação , Descolamento Retiniano/diagnóstico , Estudos Retrospectivos , Fatores de Tempo , Transplante Homólogo , Acuidade Visual/fisiologia , Adulto JovemRESUMO
Purpose: To investigate oxidative stress markers in tears and serum of patients with ocular rosacea and to examine their association with both ocular surface parameters and cutaneous rosacea subtypes. Methods: This prospective study includes rosacea patients with ocular involvement and healthy controls. We performed ophthalmological examination of all participants and collected tear breakup time (TBUT), Schirmer, Meibomian gland dysfunction (MGD) and Ocular Surface Disease Index (OSDI) scores. We quantified the total antioxidant status (TAS), total oxidant status (TOS), and arylesterase (ARE) levels from tear and serum samples, and calculated the oxidative stress index (OSI). We also classified patients into phymatous, erythematotelangiectatic, papulopustular subtypes. Results: We included 90 ocular rosacea patients and 30 healthy controls. Oxidative stress (TOS, OSI) levels were significantly higher (P < 0.01) and antioxidant levels (TAS, ARE) were significantly lower (P < 0.01) in both tear and serum samples of ocular rosacea patients as compared to controls. We found a significant positive correlation between the tear and serum values regarding oxidative stress parameters (P < 0.05). Besides, OSI was negatively correlated with TBUT and positively correlated with MGD score (meiboscore) and OSDI (P < 0.05). The Schirmer score was not correlated with OSI. No difference was found between the cutaneous subtypes with respect to TAS, TOS, ARE, and OSI results. Conclusions: In this study, we identified oxidative stress markers in the serum and tears of ocular rosacea patients and showed their correlation with clinical signs of MGD, suggesting that oxidative stress contributes to ocular rosacea pathogenesis and that oxidative stress could be an indicator of MGD severity.
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Síndromes do Olho Seco , Disfunção da Glândula Tarsal , Rosácea , Humanos , Antioxidantes/metabolismo , Estudos Prospectivos , Disfunção da Glândula Tarsal/metabolismo , Lágrimas , Glândulas Tarsais/metabolismo , Rosácea/complicações , Rosácea/diagnóstico , Estresse Oxidativo , OxidantesRESUMO
PURPOSE: To evaluate a desiccation protocol for the long-term preservation of human small incision lenticule extraction (SMILE) lenticules and to study their integration in an in vivo rabbit model. METHODS: Lenticules were retrieved after SMILE procedures in patients, then desiccated according to a novel protocol. Histologic and electron microscopic analyses were performed. Six rabbit eyes received grafts with an inlay technique, which consisted of inserting a desiccated lenticule into a stromal pocket. Rabbits were killed at different times between 6 and 24 weeks. Rabbit corneas were analyzed using optical coherence tomography, histology, and DAPI staining. RESULTS: Microscopic analysis of desiccated lenticules showed a preserved stromal architecture after rehydration. A decellularization of the lenticules after desiccation was observed without any chemical treatment. All rabbit corneas remained clear after grafting human lenticules and no rejection occurred. Optical coherence tomography showed regular lenticular implantation and no decrease in lenticule thickness. Histologic analysis showed no inflammatory infiltration around lenticules and no nuclear material inside lenticules after 6 months. CONCLUSIONS: A favorable integration of desiccated human SMILE lenticules in rabbit corneas was observed. The refractive issue of lenticular implantation must be investigated next. Clinical trials are needed to evaluate the use of desiccated SMILE lenticules to treat hyperopia or keratoconus in humans. [J Refract Surg. 2023;39(7):491-498.].
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Substância Própria , Cirurgia da Córnea a Laser , Humanos , Animais , Coelhos , Substância Própria/patologia , Dessecação , Cirurgia da Córnea a Laser/métodos , Córnea/cirurgia , Refração OcularRESUMO
The exact link between systemic and ocular endogenous corticoids (steroidome) is unclear and whether the ocular steroidome is altered in CSCR eyes is unknown. The aims of this study were to analyze the human steroidome in the aqueous humor as a function of age, sex and time of the day, to correlate systemic and ocular steroidome and to analyze the ocular steroidome in long lasting complex inactive CSCR. Based on our results, we present two CSCR cases treated by the combination of oral mineralocorticoid antagonist and glucocorticoids drops. In a cross-sectional study, aqueous humor (AH) was collected between 8am and 6 pm from 50 unaffected individuals (25 men and 25 women) and from 14 patients with chronic CSCR, during cataract surgery. In addition, simultaneous serum and AH were collected from 27 individuals undergoing cataract surgery and, simultaneous AH and vitreous were collected from 9 patients undergoing cataract and vitrectomy to estimate corticoids levels in the different compartments. The steroidome was determined using a LC-MS/MS method that quantifies 13 endogenous corticoids from the gluco, mineralocorticoid and androgen pathways. In AH and vitreous, the highest corticoid level is reached by cortisol (F), that represents less than 10% of F serum level. The cortisol levels in the serum did not correlate with ocular cortisol levels. Serum and ocular cortisone (E) levels correlate, although less than 5% of circulating E reaches the eye. The only mineralocorticoids measured in the AH were corticosterone (B) and its inactive form, the 11-desoxycorticosterone (A). There was no influence of circadian rhythm on cortisol ocular levels and there was no correlation between the age or the sex and the level of F, E, A, and B. In eyes with chronic inactive CSCR, the levels of the active glucocorticoid form F was lower than in control eyes and the F/E ratio was reduced by 50% but the B/A ratio was higher indicating imbalance towards active mineralocorticoids. Base on this observation, we propose to combine an antagonist of the mineralocorticoid receptor together with topical glucocorticoids in two CSCR patients, resistant to all other treatments, with favorable outcome. Our results indicate that the ocular psteroidome is highly regulated suggesting a local metabolism of ocular corticoids. In eyes with long-lasting complex inactive CSCR, the steroidome analysis shows lower active glucocorticoids and higher active mineralocorticoids.
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Catarata , Coriorretinopatia Serosa Central , Masculino , Humanos , Feminino , Coriorretinopatia Serosa Central/tratamento farmacológico , Glucocorticoides , Mineralocorticoides , Hidrocortisona , Cromatografia Líquida , Estudos Transversais , Espectrometria de Massas em TandemRESUMO
Abnormal corneal wound healing can compromise corneal transparency and lead to visual impairment. Mineralocorticoid receptor antagonists (MRA) are promising candidates to promote corneal remodeling with anti-inflammatory properties and lack gluococorticoids-associated side effects. In this preclinical study, a new polymer-free hydroxypropyl-gamma-cyclodextrin-based eyedrop containing 0.1% spironolactone (SPL), a potent but non-water-soluble MRA, was investigated for its ocular surface tolerance and efficacy in a rat model of corneal wound healing. SPL eyedrops were stable for up to 9 months at 4 °C. The formulation was well-tolerated since no morphological changes or inflammatory reactions were observed in the rat cornea after multiple daily instillations over 7 days. SPL eyedrops accelerated rat corneal wound healing, reduced corneal edema and inflammation, enhanced epithelial integrity, and improved nerve regeneration, suggesting restoration of corneal homeostasis, while potassium canrenoate, an active and soluble metabolite of SPL, had no effect. SPL eyedrops could benefit patients with impaired corneal wound healing, including that secondary to glucocorticoid therapy. Repurposing known drugs with known excipients will expedite translation to the clinic.
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INTRODUCTION: Keratoconus has a significant impact on patients' quality of life (QoL), from diagnosis to the advanced stages of the disease. The aim of this research was to identify domains of QoL affected by this disease and its treatment. METHODS: Phone interviews were conducted using a semi-structured interview guide, with patients with keratoconus stratified according to their current treatment. A board of keratoconus experts helped identify the guide's main themes. RESULTS: Thirty-five patients (rigid contact lenses, n = 9; cross-linking, n = 9; corneal ring implants, n = 8; and corneal transplantation, n = 9) were interviewed by qualitative researchers. Phone interviews revealed several QoL domains affected by the disease and its treatments: "psychological", "social life", "professional life", "financial costs" and "student life". All domains were impacted, independently of the treatment history. Few differences were found between treatment regimens and keratoconus stages. Qualitative analysis enabled the development of a conceptual framework based on Wilson and Cleary's model for patient outcomes common to all patients. This conceptual model describes the relationship between patients' characteristics, their symptoms, their environment, their functional visual impairment and the impact on their QoL. CONCLUSIONS: These qualitative findings supported the generation of a questionnaire to evaluate the impact of keratoconus and its treatment on patients' QoL. Cognitive debriefings confirmed its content validity. The questionnaire is applicable for all stages of keratoconus and treatments and may help tracking change over time in regular clinical settings. Psychometric validation is yet to be performed before its use in research and clinical practices.
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PURPOSE: To compare the effect of a rat anti-VEGF antibody, administered either by topical or subconjunctival (SC) routes, on a rat model of corneal transplant rejection. METHODS: Twenty-four rats underwent corneal transplantation and were randomized into four treatment groups (n=6 in each group). G1 and G2 received six SC injections (0.02 ml 10 µg/ml) of denatured (G1) or active (G2) anti-VEGF from Day 0 to Day 21 every third day. G3 and G4 were instilled three times a day with denatured (G3) or active (G4) anti-VEGF drops (10 µg/ml) from Day 0 to Day 21. Corneal mean clinical scores (MCSs) of edema (E), transparency (T), and neovessels (nv) were recorded at Days 3, 9, 15, and 21. Quantification of neovessels was performed after lectin staining of vessels on flat mounted corneas. RESULTS: Twenty-one days after surgery, MCSs differed significantly between G1 and G2, but not between G3 and G4, and the rejection rate was significantly reduced in rats receiving active antibodies regardless of the route of administration (G2=50%, G4=66.65% versus G1 and G3=100%; p<0.05). The mean surfaces of neovessels were significantly reduced in groups treated with active anti-VEGF (G2, G4). However, anti-VEGF therapy did not completely suppress corneal neovessels. CONCLUSIONS: Specific rat anti-VEGF antibodies significantly reduced neovascularization and subsequent corneal graft rejection. The SC administration of the anti-VEGF antibody was more effective than topical instillation.
Assuntos
Córnea/imunologia , Transplante de Córnea/métodos , Fator A de Crescimento do Endotélio Vascular/imunologia , Animais , Neovascularização da Córnea/prevenção & controle , Edema/patologia , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Masculino , Neovascularização Patológica/prevenção & controle , Distribuição Aleatória , Ratos , Ratos Endogâmicos Lew , Fator A de Crescimento do Endotélio Vascular/químicaRESUMO
PURPOSE: Investigate the genotype-phenotype correlations for five TGFBI (transforming growth factor, beta-induced) mutations including one novel pathogenic variant and one complex allele affecting the fourth FAS1 domain of keratoepithelin, and their potential effects on the protein's structure. METHODS: Three unrelated families were clinically diagnosed with lattice corneal dystrophy (CD) and one with an unclassified CD of Bowman's layer. Mutations in the TGFBI gene were detected by direct sequencing, and the functional impact of each variant was predicted using in silico algorithms. Corneal phenotypes, including histological examinations, were compared with the literature data. Furthermore, molecular modeling studies of these mutations were performed. RESULTS: Two distinct missense mutations affecting the same residue at position 509 of keratoepithelin: p.Leu509Pro (c.1526T>C) and p.Leu509Arg (c.1526T>G) were found to be associated with a lattice-type CD. The novel p.Val613Gly (c.1828T>G) TGFBI mutation was found in a sporadic case of an Algerian individual affected by lattice CD. Finally, the Bowman's layer CD was linked to the association in cis of the p.Met502Val and p.Arg555Gln variants, leading to the reclassification of this CD as atypical Thiel-Behnke CD. Structural modeling of these TGFBI mutations argues in favor of these mutations being responsible for instability and/or incorrect folding of keratoepithelin, predictions that are compatible with the clinical diagnoses. CONCLUSIONS: Description of a novel TGFBI mutation and a complex TGFBI allele further extends the mutational spectrum of TGFBI. Moreover, we show convincing evidence that TGFBI mutations affecting Leu509 are linked to the lattice phenotype in two unrelated French families, contrasting with findings previously reported. The p.Leu509Pro was reported to be associated with both amyloid and non-amyloid aggregates, whereas p.Leu509Arg has been described as being responsible for Epithelial Basement Membrane Dystrophy (EBMD).
Assuntos
Lâmina Limitante Anterior/metabolismo , Distrofias Hereditárias da Córnea/genética , Proteínas da Matriz Extracelular/genética , Fator de Crescimento Transformador beta/genética , Adulto , Idoso de 80 Anos ou mais , Argélia/etnologia , Alelos , Sequência de Aminoácidos , Lâmina Limitante Anterior/patologia , Distrofias Hereditárias da Córnea/classificação , Distrofias Hereditárias da Córnea/epidemiologia , Distrofias Hereditárias da Córnea/etnologia , Distrofias Hereditárias da Córnea/patologia , Proteínas da Matriz Extracelular/metabolismo , Feminino , França/epidemiologia , Frequência do Gene , Estudos de Associação Genética , Ligação Genética , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Dados de Sequência Molecular , Mutação , Linhagem , Fenótipo , Fator de Crescimento Transformador beta/metabolismoRESUMO
PURPOSE: Robotic intraocular microsurgery requires a remote center of motion (RCM) at the site of ocular penetration. We designed and tested the Hexapod Surgical System (HSS), a microrobot mounted on the da Vinci macrorobot for intraocular microsurgery. MATERIAL AND METHODS: Translations and rotations of the HSS were tested for range of motion and stability. Precision and dexterity were assessed by pointing and inserting a coupled probe into holes of various sizes. The stability of a nonmechanical RCM was quantified. HSS functionalities were observed on porcine eyes. RESULTS: The HSS maximal translations were 10 (x and y axes) and 5 cm (z axis). The maximal rotations were 15 and 22° (x and y axes). The precision was within 0.5 mm away from targets in 26/30 tests and maximal in 16/30 tests. The mean translational and rotational stability at the tip of the probe were 1.2 (0.6-1.9) and 1 mm (0-2), respectively. The average dexterity times were 5.2 (4.4-6.5), 7.1 (5.6-10.8) and 12.3 s (7.8-21.7) for 5-, 2- and 1-mm holes, respectively. The RCM was stable (within 0.1 mm). A vitreous cutter coupled to the HSS moved into porcine eyes through a sclerotomy with a stable RCM. CONCLUSION: The HSS provides an RCM dedicated for intraocular robotic surgery with a high level of precision and dexterity. Although it can be further improved, the micro-macro robotic system is a feasible approach for ocular surgery.