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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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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.
ABSTRACT
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.
Subject(s)
Epithelium, Corneal , Keratoconus , Cornea/metabolism , Cornified Envelope Proline-Rich Proteins/metabolism , Epithelium, Corneal/metabolism , Humans , Keratins/metabolism , Keratoconus/genetics , Keratoconus/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Oxidative Stress/geneticsABSTRACT
INTRODUCTION: We performed a prospective, single-center, cohort study in order to evaluate the effects of vitrectomy with epiretinal membrane (ERM) peel on optical quality in patients with primary ERM. METHODS: Thirty patients treated for primary ERM by vitrectomy with ERM peel were included from our tertiary university hospital ophthalmology department. The main study outcome was a variation in optical quality parameters measured using the HD Analyzer™ between preoperative and 2-month postoperative evaluations in operated eyes. Optical quality parameters comprised point spread function (PSF) width at 10% and 50%, objective scatter index (OSI), and modulation transfer function (MTF) cutoff. Contralateral non-operated eyes were used as an internal control for measurement reproducibility. RESULTS: Mean PSF width at 10% (42.22 vs. 27.37 arc/min; p = 0.0002) and mean OSI (3.32 vs. 2.32; p = 0.0003) were significantly improved between pre- versus postoperative evaluations. Mean PSF width at 50% and mean MTF cutoff showed no changes. Subgroup analysis according to crystalline lens status gave similar results, demonstrating that improvements in mean PSF width at 10% and OSI were not lens-related. Non-operated eyes showed no changes in any of the parameters analyzed. CONCLUSION: Reduced light scattering measured by OSI indicates improved optical quality following vitrectomy with ERM peel among patients with primary ERM. OSI measurement could thus be a new parameter of interest in the preoperative assessment of primary ERM and other pre-vitrectomy assessments.
Subject(s)
Epiretinal Membrane , Aberrometry/methods , Cohort Studies , Epiretinal Membrane/diagnosis , Epiretinal Membrane/etiology , Epiretinal Membrane/surgery , Humans , Prospective Studies , Reproducibility of Results , Retrospective Studies , Tomography, Optical Coherence/methods , Visual Acuity , Vitrectomy/methodsABSTRACT
BACKGROUND: Because of the implications of Receptor for Advanced Glycation End Products (RAGE) in keratoconus (KC), we describe a differential expression of RAGE transcripts and proteins in corneal tissues and tears of KC and healthy patients. METHODS: Using a case-controlled study, corneal epitheliums and tears of KC and healthy subjects were obtained during corneal collagen cross-linking and photorefractive keratectomy (PKR) and during usual consultations. Quantitative reverse transcription (RT-qPCR) and Western-Blot were performed to analyze RAGE transcripts and proteins' expression in corneal tissues and tears. RESULTS: One hundred and six patients were included in this study. The characteristics of the patients were as follows: 56 KC (25 corneal epithelium and 31 tears) and 50 control subjects (25 corneal epithelium and 25 tears). Transcripts of RAGE, HMGB1, and S100 family ligands were quantified by RT-qPCR, identifying a significantly higher expression of RAGE and HMGB1 in the healthy group than in the KC group (p = 0.03 and 0.04, respectively). Western Blot showed a significantly higher fl-RAGE expression in KC corneal epithelium than control (p < 0.001) and lower s-RAGE expression in KC tears than control (p = 0.04). CONCLUSIONS: Linked with the inflammatory process occurring in KC pathophysiology, we propose for the first time that the RAGE expression (total and truncated forms of receptor and ligands) in KC corneal tissues and tear samples provides viable biomarkers.
Subject(s)
Epithelium, Corneal/metabolism , Glycation End Products, Advanced/metabolism , Keratoconus/metabolism , Receptor for Advanced Glycation End Products/metabolism , Biomarkers/metabolism , Case-Control Studies , Cornea/metabolism , Female , Humans , Male , Tears/metabolismABSTRACT
PURPOSE: To assess a new polynomial regression formula integrating the refractive prediction error of the first-operated eye to improve the intraocular lens power calculation of the second eye in cataract surgery. SETTING: Centre Hospitalier Universitaire, Toulouse, France. DESIGN: Retrospective multicentric dataset study. METHODS: A polynomial regression formula, WeOptimeye2nd (WO2nd), was developed using a machine-learning algorithm trained on a dataset of 534 patients who underwent sequential bilateral cataract surgery. A separate multicentric dataset was used to retrospectively calculate predicted refraction with WO2nd, SRK/T and Barrett Universal II formulas, and 3 other methods of constant factors (CFs) second-eye refinement (CF0.38, CF0.35, and CF0.5). Mean absolute errors (MAEs) and percentage of eyes within ±0.25, ±0.5, and ±1.0 diopter (D) from predicted spherical equivalent were compared between formulas. RESULTS: The study comprised data on 722 patients. In the overall population, WO2nd had the lowest MAE: 0.339 vs 0.347 (P = .137), 0.340 (P = .956), 0.350 (P = .066), 0.399 (P < .001), and 0.410 (P < .001), with CF0.38, CF0.5, and CF0.35, Barrett II, and SRK/T, respectively. WO2nd had the highest percentage of eyes within ±0.5 D of the predicted refraction, and the difference was statistically significant vs SRK/T and Barrett II formulas but not vs CF0.38, CF0.5, and CF0.35. WO2nd performed the best in axial length (AL) < 22 mm with the lowest MAE and a statistically significant difference vs any other formula. CONCLUSIONS: WO2nd improved the refractive outcome of the second-operated eye and performed well in extreme AL and mean keratometry subgroups.
Subject(s)
Cataract , Lenses, Intraocular , Refractive Errors , Algorithms , Axial Length, Eye , Biometry/methods , Humans , Lens Implantation, Intraocular/methods , Optics and Photonics , Refraction, Ocular , Retrospective StudiesABSTRACT
The involvement of genetic factors in the pathogenesis of KC has long been recognized but the identification of variants affecting the underlying protein functions has been challenging. In this study, we selected 34 candidate genes for KC based on previous whole-exome sequencing (WES) and the literature, and resequenced them in 745 KC patients and 810 ethnically matched controls from Belgium, France and Italy. Data analysis was performed using the single variant association test as well as gene-based mutation burden and variance components tests. In our study, we detected enrichment of genetic variation across multiple gene-based tests for the genes COL2A1, COL5A1, TNXB, and ZNF469. The top hit in the single variant association test was obtained for a common variant in the COL12A1 gene. These associations were consistently found across independent subpopulations. Interestingly, COL5A1, TNXB, ZNF469 and COL12A1 are all known Ehlers-Danlos Syndrome (EDS) genes. Though the co-occurrence of KC and EDS has been reported previously, this study is the first to demonstrate a consistent role of genetic variants in EDS genes in the etiology of KC. In conclusion, our data show a shared genetic etiology between KC and EDS, and clearly confirm the currently disputed role of ZNF469 in disease susceptibility for KC.
Subject(s)
Ehlers-Danlos Syndrome/genetics , Keratoconus/genetics , Collagen Type II/genetics , Collagen Type V/genetics , Ehlers-Danlos Syndrome/diagnosis , Humans , Keratoconus/diagnosis , Sequence Analysis, DNA , Tenascin/genetics , Transcription Factors/geneticsABSTRACT
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.].
Subject(s)
Keratoconus , Photochemotherapy , Collagen/therapeutic use , Corneal Pachymetry , Corneal Topography , Cross-Linking Reagents/therapeutic use , Humans , Keratoconus/drug therapy , Oxygen , Photosensitizing Agents/therapeutic use , Pilot Projects , Prospective Studies , Riboflavin/therapeutic use , Ultraviolet RaysABSTRACT
PURPOSE: To conduct a systematic review and meta-analysis on the levels of oxidative stress markers and antioxidants in keratoconus compared to healthy subject. METHOD: The PubMed, Cochrane Library, Embase, Science Direct and Google Scholar databases were searched on 1st June 2020 for studies reporting oxidative and antioxidative stress markers in keratoconus and healthy controls. Main meta-analysis was stratified by type of biomarkers, type of samples (tears, cornea, aqueous humour and blood) and type of corneal samples (stromal cells, epithelium and endothelium). RESULTS: We included 36 articles, for a total of 1328 keratoconus patients and 1208 healthy controls. There is an overall increase in oxidative stress markers in keratoconus compared with healthy controls (standard mean deviation (SMD) = 0.94, 95% confidence interval (95% CI) 0.55-1.33), with a significant increase in reactive oxygen and nitrogen species (1.09, 0.41-1.78) and malondialdehyde (1.78, 0.83-2.73). There is an overall decrease in antioxidants in keratoconus compared with healthy controls (-0.63, -0.89 to -0.36), with a significant decrease in total antioxidant capacity/status (-1.65, -2.88 to -0.43), aldehyde/NADPH dehydrogenase (-0.77, -1.38 to -0.17), lactoferrin/transferrin/albumin (-1.92, -2.96 to -0.89) and selenium/zinc (-1.42, -2.23 to -0.61). Oxidative stress markers were higher in tears and in cornea of keratoconus than in aqueous humour, and antioxidants were decreased in tears, aqueous humour and blood without difference between sample type. Oxidative stress markers increased in stromal cells and antioxidants decreased in endothelium. CONCLUSION: Oxidative stress markers and antioxidants were dysregulated in keratoconus, involving an imbalance of redox homeostasis in tears, cornea, aqueous humour and blood.
Subject(s)
Antioxidants/metabolism , Aqueous Humor/metabolism , Cornea/metabolism , Keratoconus/metabolism , Oxidative Stress , Tears/metabolism , Biomarkers/metabolism , HumansABSTRACT
PURPOSE: To assess the keratoconus (KC) prevalence among first-degree relatives of affected subjects. METHODS: We performed large epidemiological, prospective, and observational cohort, which took place in the French KC National Reference Centre, in Bordeaux. We studied data from 94 unrelated patients with KC and at least 2 first-degree relatives assessable. Each subject had a thorough ocular examination including visual acuity, refraction, slitlamp biomicroscopy, indirect ophthalmoscopy, keratometry, corneal topography and tomographer (Topographic Modeling System; Tomey Corporation, Japan; and Galilei G4, Ziemer, Switzerland, respectively), pachymetry, and biomechanical properties of cornea (Ocular Response Analyzer; Reichert, Depew, NY). Additional data were collected about atopy, smoking, and eye-rubbing habits. KC prevalence, multivariate analysis, and familial correlation analysis have been studied. RESULTS: Of the 221 relatives, 9.05% (n = 20) had clinically manifest KC, and 15.4% (n = 31) had subclinical KC. The prevalence of KC was estimated equal to 0.14 [95% confidence interval (CI), 0.07-0.22] among parents, 0.03 (95% CI, 0-0.10) among offspring, and 0.10 (95% CI, 0.04-0.20) among siblings. In multivariable analysis, age and eye-rubbing were associated with an increased risk of KC. The familial correlation of KC among probands' first-degree relatives was estimated at 0.55 among parents, 0.29 among offspring, and 0.49 among siblings. CONCLUSIONS: Being a first-degree relative of a subject with KC remains a risk factor for developing KC. This should be taken into account especially when screening for KC in pediatric patients, for refractive surgery candidates, and for patients being evaluated for cataract surgery.
Subject(s)
Family Health/statistics & numerical data , Keratoconus/epidemiology , Adolescent , Adult , Child , Corneal Pachymetry , Corneal Topography , Female , France/epidemiology , Humans , Keratoconus/diagnosis , Keratoconus/physiopathology , Male , Middle Aged , Ophthalmoscopy , Prevalence , Prospective Studies , Risk Factors , Slit Lamp Microscopy , Visual Acuity/physiology , Young AdultABSTRACT
PURPOSE: Contact lens (CL)-related microbial keratitis (MK) has major public health implications, with about 300 million wearers worldwide, and certain potentially modifiable risk factors. This study aimed to identify the risk factors of CL-related MK. METHODS: A multicenter case-control study was conducted between 2014 and 2017. Cases presenting with CL-related MK were submitted to an anonymous 52-item questionnaire, which was also completed by healthy controls. Univariate followed by multivariate logistic regression analysis was performed. Risk factors for CL-related MK were given as odds ratio (OR) with 95% confidence interval and P-value. RESULTS: The study included a total of 2267 patients (1198 cases and 1069 controls). The MK risk factors for the daily disposable lenses group were exceeding the lens renewal period (OR = 9.16, P = 0.008) and occasionally wearing CL when sleeping (OR = 15.83, P = 0.035). The most important risk factors in the nondaily disposable lenses group were lens cleaning solution distributed by eye care brands (OR = 3.50, P < 0.001) and failure to renew lens cases (OR = 3.39, P = 0.001). Statistically and clinically significant variables were used to establish the MK risk equation for CL wearers, allowing an individual calculation of the risk of MK under lenses. CONCLUSIONS: The MK risk equation is a valuable tool for educating patients about the risks associated with wearing CL. It allows the patient to be informed about their overall risk of infection while detailing the precipitating elements of the infectious risk with the aim of modifying risk behavior.
Subject(s)
Bacteria/isolation & purification , Contact Lenses/adverse effects , Eye Infections, Bacterial/etiology , Hygiene/standards , Keratitis/etiology , Risk Assessment/methods , Adult , Biometry , Case-Control Studies , Contact Lenses/microbiology , Eye Infections, Bacterial/microbiology , Eye Infections, Bacterial/prevention & control , Female , Humans , Keratitis/microbiology , Keratitis/prevention & control , Male , Risk Factors , Surveys and QuestionnairesABSTRACT
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.
Subject(s)
Cross-Linking Reagents/therapeutic use , Epithelium, Corneal/surgery , Myopia/therapy , Photochemotherapy/methods , Photorefractive Keratectomy/methods , Refraction, Ocular/physiology , Riboflavin/therapeutic use , Adult , Corneal Stroma , Corneal Topography , Female , Follow-Up Studies , Humans , Male , Myopia/pathology , Photosensitizing Agents/therapeutic use , Pilot Projects , Prospective Studies , Visual AcuityABSTRACT
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.
Subject(s)
Lens Implantation, Intraocular/methods , Multifocal Intraocular Lenses , Phacoemulsification/methods , Pseudophakia/surgery , Aged , Aged, 80 and over , Anterior Chamber/diagnostic imaging , Cell Count , Contrast Sensitivity/physiology , Endothelium, Corneal/cytology , Female , Humans , Intraocular Pressure/physiology , Male , Microscopy, Acoustic , Middle Aged , Patient Satisfaction , Prospective Studies , Pseudophakia/physiopathology , Surveys and Questionnaires , Tomography, Optical Coherence , Visual Acuity/physiologyABSTRACT
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.
Subject(s)
Corneal Opacity/surgery , Keratoplasty, Penetrating/methods , Lasers, Excimer/therapeutic use , Cicatrix/surgery , Female , Humans , Male , Pilot Projects , Prospective Studies , Young AdultABSTRACT
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.
Subject(s)
Corneal Diseases/surgery , Lens Implantation, Intraocular/methods , Lenses, Intraocular , Sclera/surgery , Visual Acuity , Adolescent , Adult , Aged , Child , Child, Preschool , Corneal Diseases/diagnosis , Corneal Diseases/physiopathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Prosthesis Design , Treatment Outcome , Young AdultABSTRACT
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.].
Subject(s)
Collagen/pharmacology , Corneal Stroma/pathology , Cross-Linking Reagents/pharmacology , Keratoconus/drug therapy , Photochemotherapy/methods , Riboflavin/pharmacology , Visual Acuity , Corneal Pachymetry , Corneal Topography , Female , Follow-Up Studies , Humans , Keratoconus/diagnosis , Male , Microscopy, Confocal , Photosensitizing Agents/pharmacology , Prospective Studies , Tomography, Optical Coherence , Ultraviolet Rays , Young AdultABSTRACT
PURPOSE: To assess the quality of life in French keratoconus patients. SETTING: Fifty-seven Keratoconus National Reference Centers across France. DESIGN: Prospective case series. METHODS: Patients completed the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) and a French validated questionnaire on disability and dependency from February to June 2012 when they came for an ophthalmic examination at 57 participating centers across France. An ocular examination including refraction, corneal topography, pachymetry, and slitlamp biomicroscopy was performed. The composite or global NEI VFQ-25 score and the proportion of patients who were dependent (defined by the difficulties with activities of daily living) because of keratoconus were the main evaluation criteria in this study. RESULTS: The study comprised 550 keratoconus patients. Women, corrected distance visual acuity worse than 20/40, steep keratometry higher than 52.0 diopters, history of surgery (corneal transplant, intrastromal corneal ring segments, or corneal crosslinking), and more severe keratoconus according to the Amsler-Krumeich classification were associated with an increasingly negative impact on quality of life (overall scores are significantly lower). Moreover, 4.9% of participants reported having changed their jobs because of keratoconus and 7.8% received keratoconus-related disability. Sixty-nine (12.5%) patients reported having difficulties with activities of daily living and are considered dependent. CONCLUSION: Keratoconus was associated with a significant reduction in quality of life but it did not result in social exclusion.
Subject(s)
Keratoconus , Quality of Life , Activities of Daily Living , France , Humans , Keratoconus/surgery , Prospective Studies , Prostheses and Implants , Vision, Ocular , Visual AcuityABSTRACT
Inflammasome complexes function as key innate immune effectors that trigger inflammation in response to pathogen- and danger-associated signals. Here, we report that germline mutations in the inflammasome sensor NLRP1 cause two overlapping skin disorders: multiple self-healing palmoplantar carcinoma (MSPC) and familial keratosis lichenoides chronica (FKLC). We find that NLRP1 is the most prominent inflammasome sensor in human skin, and all pathogenic NLRP1 mutations are gain-of-function alleles that predispose to inflammasome activation. Mechanistically, NLRP1 mutations lead to increased self-oligomerization by disrupting the PYD and LRR domains, which are essential in maintaining NLRP1 as an inactive monomer. Primary keratinocytes from patients experience spontaneous inflammasome activation and paracrine IL-1 signaling, which is sufficient to cause skin inflammation and epidermal hyperplasia. Our findings establish a group of non-fever inflammasome disorders, uncover an unexpected auto-inhibitory function for the pyrin domain, and provide the first genetic evidence linking NLRP1 to skin inflammatory syndromes and skin cancer predisposition.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Apoptosis Regulatory Proteins/genetics , Carcinoma/genetics , Genetic Predisposition to Disease , Inflammasomes/metabolism , Keratosis/genetics , Skin Neoplasms/genetics , Adaptor Proteins, Signal Transducing/chemistry , Amino Acid Sequence , Apoptosis Regulatory Proteins/chemistry , Carcinoma/pathology , Chromosomes, Human, Pair 17/genetics , Epidermis/pathology , Germ-Line Mutation , Humans , Hyperplasia/genetics , Hyperplasia/pathology , Inflammasomes/genetics , Interleukin-1/metabolism , Keratosis/pathology , NLR Proteins , Paracrine Communication , Pedigree , Protein Domains , Pyrin/chemistry , Signal Transduction , Skin Neoplasms/pathology , SyndromeABSTRACT
The cornea represents the external part of the eye and consists of an epithelium, a stroma and an endothelium. Due to its curvature and transparency this structure makes up approximately 70% of the total refractive power of the eye. This function is partly made possible by the particular organization of the collagen extracellular matrix contained in the corneal stroma that allows a constant refractive power. The maintenance of such an organization involves other molecules such as type V collagen, FACITs (fibril-associated collagens with interrupted triple helices) and SLRPs (small leucine-rich proteoglycans). These components play crucial roles in the preservation of the correct organization and function of the cornea since their absence or modification leads to abnormalities such as corneal opacities. Thus, the aim of this review is to describe the different corneal collagens and proteoglycans by highlighting their importance in corneal transparency as well as their implication in corneal visual disorders.
Subject(s)
Collagen/metabolism , Cornea/metabolism , Proteoglycans/metabolism , Vision Disorders/metabolism , Animals , Cornea/pathology , Cornea/physiopathology , Humans , Models, Biological , Vision Disorders/physiopathology , Wound HealingABSTRACT
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.