Whole exome sequencing identifies a mutation for a novel form of corneal intraepithelial dyskeratosis.

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.

[Ethical and legal aspects of telemedicine]. / Éthique, jurisprudence et telemedicine.

The recent development of telemedicine, i.e. the use of communication technologies to transfer medical information, raises special ethical and legal issues. The HPST law regulates the delivery of remote healthcare in France. The ethical aspects of telemedicine are similar in many respects to those of conventional medicine, but the involvement of non clinical personnel and the use of technologies raise special issues such as confidentiality. Patients must be informed of these issues and their consent must be sought before employing telemedicine procedures. Finally, in case of malpractice complaints, the respective liabilities of the different disciplines involved in telemedicine must be determined

[Keratoconus, the most common corneal dystrophy. Can keratoplasty be avoided?]. / La plus commune des dystrophies cornéennes: le kératocône. Peut-on éviter la greffe?

Keratoconus is the most common form of corneal dystrophy. It consists of a non inflammatory progressive thinning process that leads to conical ectasia of the cornea, causing high myopia and astigmatism. In more advanced cases, opacities can be seen at the apex of the cone. Traditional conservative management of keratoconus begins with spectacle correction and contact lenses. Surgery is recommended when a stable contact lens fit fails to provide adequate vision. Keratoplasty was long the only surgical treatment, but recent years have seen the introduction of new surgical options:--Collagen cross-linking stiffens the cornea and can halt disease progression;--Intrastromal corneal rings can reduce astigmatism and improve visual acuity;--Intraocular lenses are valuable additional options for the correction of refractive errors. Currently, keratoplasty is mainly restricted to patients with opacities of the central cornea.

AcrySof phakic angle-supported intraocular lens for the correction of moderate-to-high myopia: one-year results of a multicenter European study.

PURPOSE: To investigate the safety and effectiveness of the AcrySof phakic angle-supported intraocular lens (IOL) (Alcon Laboratories, Inc., Fort Worth, TX) for correction of moderate-to-high myopia in adults. DESIGN: One-year interim analysis of a phase 3, nonrandomized, open-label, prospective, multicenter European clinical study. PARTICIPANTS: A total of 190 subjects (190 eyes) with moderate-to-high myopia. The preoperative mean manifest refraction spherical equivalent (MRSE) was -10.38 diopters (D) +/-2.43 standard deviation (SD). METHODS: Unilateral implantation of the AcrySof phakic angle-supported IOL. MAIN OUTCOME MEASURES: Best spectacle-corrected visual acuity (BSCVA), uncorrected distance visual acuity (UCVA), predictability and stability of MRSE, adverse events, and endothelial cell density. RESULTS: Of 190 subjects enrolled, 161 completed the 1-year postoperative visit. No subjects lost > or =2 lines BSCVA. A UCVA of 20/20 or better was achieved by 57.8%; 99.4% had 20/40 or better. A BSCVA of 20/32 or better was achieved by 100% of subjects; 85.7% had 20/20 or better. The mean MRSE was -0.23 D (+/-0.50 D: -2.50 to 0.75 D). Residual refractive error was within +/-1.0 D from the target for 95.7% of subjects and within +/-0.5 D for 72.7% of subjects. The overall mean percentage change in central endothelial cell density 1 year after surgery was -4.77+/-8.04% (n = 139). No pupil ovalization, pupillary block, or retinal detachment events were observed. CONCLUSIONS: The AcrySof phakic angle-supported IOL yielded excellent refractive correction and predictability with acceptable safety in subjects with moderate-to-high myopia. These 1-year interim analysis findings demonstrate preliminary support for the safety and efficacy of this IOL.

[Corneal lamellar graft. Back to the future]. / Greffes lamellaires de cornée. Retour vers le futur.

Transplantation of all of the corneal layers (penetrating keratoplasty) is the most common corneal grafting method, regardless of the indication. The surgical procedure is relatively simple but penetrating keratoplasty has several potential complications: --Unnecessary replacement of healthy recipient endothelium in diseases affecting only the anterior layers carries a risk of immune rejection. --Replacement of the anterior part of the cornea in diseases affecting only the posterior layers delays visual recovery Lamellar keratoplasty consists of replacing only the diseased corneal layers. Although it was the first procedure to be described, lamellar keratoplasty became less popular because it is technically difficult and often gives poor visual results due to imperfect lamellar dissection. Recent surgical advances have overcome these difficulties, and lamellar keratoplasty may well become the first-choice treatment for most stromal and endothelial diseases.

Inadequate results for microkeratome-assisted additive stromal keratoplasty for management of keratoconus.

PURPOSE: To evaluate a new automated technique--microkeratome-assisted additive stromal keratoplasty (MASK)--for the management of keratoconus in eyes scheduled for surgery with clear cornea associated with total contact lens intolerance. METHODS: This non-comparative, interventional case series included four eyes of four patients with stage I and II keratoconus associated with total contact lens intolerance. The first step of the surgical procedure consisted of performing a nasal-hinged flap on the host cornea with a microkeratome. The second step consisted of extracting a stromal piano-powered disk from the donor's cornea using an artificial chamber. The 80-microm thick lamellar graft was punched with a 7.5-mm circular trephine and positioned beneath the flap. Corneal refractive surgery was scheduled for the end of the sixth postoperative month. RESULTS: No corneal refractive surgery was performed after 6 months of follow-up. Only one eye gained five lines of best spectacle-corrected visual acuity (BSCVA). Among the other three eyes, two had unchanged BSCVA and one lost one line of BSCVA. At the end of surgery, mean corneal thickness was increased by 148.75 microm. CONCLUSIONS: Microkeratome-assisted additive stromal keratoplasty appears to be a safe and straightforward surgical technique that preserves the host endothelium and avoids the need of an open-sky procedure. However, in our study, MASK is not considered as an alternative to penetrating or deep lamellar keratoplasty in the management of keratoconus with clear cornea because of imprecise anatomic and refractive outcomes.

Late-onset hyaloideocapsular block syndrome.

PURPOSE: To report an unusual cause of decreased vision in an aphakic patient. DESIGN: Interventional case report. PARTICIPANT: One patient. INTERVENTION: An 80-year-old woman presented with a myopic shift and decreased visual acuity in the left eye 16 years after extracapsular cataract extraction (ECCE) without intraocular lens (IOL) implantation. Slit-lamp examination after pupil dilation revealed a milky fluid accumulation between the posterior lens capsule and the anterior hyaloid membrane. A neodymium:yttrium-aluminium-garnet (Nd:YAG) laser hyaloidotomy was performed on the anterior hyaloid membrane. MAIN OUTCOME MEASURES: Refraction and best-corrected visual acuity. RESULTS: The Nd:YAG laser hyaloidotomy allowed the trapped fluid to flow into the vitreous cavity. The myopic shift disappeared immediately and visual acuity improved. CONCLUSIONS: To our knowledge, this is the first report of a late-onset hyaloideocapsular block syndrome after ECCE without IOL implantation.

Pyoderma gangrenosum with necrotizing sclerokeratitis after cataract surgery.

A 78-year-old man who had had uneventful extracapsular cataract extraction in the left eye 3 months earlier developed pyoderma gangrenosum (PG)-associated peripheral ulcerative keratitis (PUK) after suture removal. The patient had a 13-year history of PG associated with monoclonal immunoglobulin-A gammopathy. He presented with extensive, painful PUK at the incision site, with a descemetocele and a high risk for perforation. Fibrin glue tissue adhesive was used to stabilize the corneal ulcer as an adjunct to topical and systemic treatment. The patient had been treated with tapering doses of prednisone and cyclophosphamide (50 mg/day). High-dose human intravenous immunoglobulin (0.4 mg/kg/d for 4 days) was administered. The ulcer healed 1 month later with a loss of visual acuity. To our knowledge, this is the first reported case of PG-associated sclerokeratitis following cataract surgery. Early recognition of this rare ocular localization of PG is important to institute the appropriate therapy.

Severe endothelial cell loss following uneventful angle-supported phakic intraocular lens implantation for high myopia.

Endothelial decompensation is a serious complication of phakic intraocular lens (pIOL) implantation and is a major concern during the postoperative period. We report 3 eyes in which the same foldable angle-supported pIOL was implanted to correct high myopia. Rapid and severe postoperative endothelial cell loss occurred in all 3 eyes. An over-sized pIOL that induced excessive vaulting into the anterior chamber was the main risk factor. In 2 eyes, the pIOL was explanted uneventfully; 1 eye required Descemet's stripping automated endothelial keratoplasty because of total endothelial decompensation. These cases illustrate the importance of accurate sizing of foldable angle-supported anterior chamber pIOLs to avoid excessive vaulting. They also highlight the importance of regular follow-up and preventive pIOL explantation as soon as significant endothelial cell loss is detected.

Corneal ectasia after photorefractive keratectomy for low myopia.

OBJECTIVE: To alert ophthalmologists of the possibility of an aggravation of forme fruste keratoconus after photorefractive keratectomy (PRK). DESIGN: Clinical case report. INTERVENTION: Standard bilateral PRK for low myopia. MAIN OUTCOME MEASURES: Corneal topography, corneal thickness, and visual acuity. RESULTS: Corneal ectasia occurred bilaterally after PRK. Retrospective analysis of preoperative videokeratography indicated the existence of forme fruste keratoconus on the left eye. CONCLUSIONS: This article is the first case report of a bilateral corneal ectasia after PRK for low myopia. Even if there is no direct proof to demonstrate that PRK has worsened the evolution of keratoconus, the safety of the PRK procedure in forme fruste keratoconus must be considered.

Iris-supported phakic lenses (rigid vs foldable version) for treating moderately high myopia: randomized paired eye comparison.

PURPOSE: To compare refractive performance of Artisan (Ophtec, Groningen, The Netherlands) or Verisyse phakic intraocular lens and its foldable version, Artiflex (Ophtec), for the correction of moderately high myopia. DESIGN: Randomized pilot study. METHODS: setting: Institutional practice. patient population: Thirty-one patients with myopia that ranged from -6 to -14 diopters (D). interventional procedure: One eye was implanted with an Artisan phakic intraocular lens (PIOL) and the other with an Artiflex PIOLs. main outcome measures: Primary outcome measure was the percentage of eyes with uncorrected visual acuity (UCVA) of >20/40 at one year after the operation. Main secondary outcome measures were the safety index, the change of two lines or more of best spectacle-corrected visual acuity (BSCVA) and the endothelial cell count. RESULTS: No intraoperative complications were noticed. One year after surgery, the percentage of eyes with UCVA of >20/40 was 51.6% (16/31 patients) for Artisan-treated eyes and 77.4% (24/31 patients) for Artiflex-treated eyes (P = .033). One month after surgery, this same percentage was 42.9% (13/31 patients) and 77.4% (24/31 patients), respectively (P = .004). The safety index at one year was 1.13 +/- 0.24 for Artisan-treated eyes and 1.12 +/- 0.21 for Artiflex-treated eyes, which is a difference that was not statistically significant (P = 0.742). At one year after surgery, the changes of two lines or more of BSCVA and the endothelial cell loss were similar for both groups. CONCLUSION: To correct moderately high myopia, the Artiflex lens provides a faster visual recovery and a better UCVA than does the Artisan lens. The safety of the lens should be supported by an enlarged sample size and a longer follow-up period.

Risk factors for development of choroidal detachment after scleral buckling procedure.

PURPOSE: To determine risk factors of choroidal detachment after scleral buckling procedure for treatment of retinal detachment. DESIGN: Retrospective chart review. METHODS: The authors performed a retrospective study of 69 consecutive cases of retinal detachment from January 2007 to January 2008 treated by scleral buckling surgery. Two groups of patients were defined according to the absence or apparition of choroidal detachment, and a comparison of several parameters between these 2 groups was performed. RESULTS: Fifteen patients developed a choroidal detachment. The study found an average higher level of systolic blood pressure during surgery in the group with choroidal detachment than in the absence group (127.3 vs 119.1 mm Hg; P = .008). The authors also observed a statistically significant difference between the 2 groups when comparing the intraoperative peak value of systolic blood pressure (149.3 vs 138.5 mm Hg; P = .019). Finally, in the group that developed choroidal detachment, there were statistically more patients with high myopia (P = .02). CONCLUSION: This study highlights that the 2 main risk factors for development of choroidal detachment during scleral buckling surgery are high blood pressure during the intervention and the existence of high myopia.

A randomized comparison of pupil-centered versus vertex-centered ablation in LASIK correction of hyperopia.

PURPOSE: To compare visual and optical outcomes of pupil-centered vs vertex-centered ablation in patients undergoing laser-assisted in situ keratomileusis (LASIK) for hyperopia. DESIGN: Randomized, double-masked, prospective, single-center trial. SETTING: Institutional practice. STUDY POPULATION: Sixty eyes of 30 patients with low and moderate hyperopia. Intervention procedure: Eyes underwent LASIK (Allegretto excimer laser). In 30 eyes, the ablation was centered on the pupil, while in the 30 other eyes the ablation was centered on the corneal reflex. MAIN OUTCOME MEASURES: Primary outcome measure was the safety index. Main secondary outcome measures were efficacy index, manifest refraction, uncorrected visual acuity, best spectacle-corrected visual acuity (BCVA), and ocular high-order aberrations for a 6-mm pupil size. RESULTS: At 3 months postoperatively, the safety index was 0.99 ± 0.04 in the pupil-centered group and 0.99 ± 0.08 in the vertex-centered group (P = .97). The efficacy index was also similar for both groups: 0.96 ± 0.05 in pupil-centered eyes and 0.93 ± 0.09 in vertex-centered eyes (P = .31). Optical aberrations were similar for pupil-centered and vertex-centered eyes. Considering only eyes showing large pupil decentration, we found a tendency for better visual results in favor of pupil-centered eyes in terms of safety index and a slight but significant increase of coma in vertex-centered eyes. CONCLUSION: LASIK is an effective procedure for treatment of hyperopia. Pupil-centered and vertex-centered treatments provide similar visual and optical outcomes. However, in eyes showing large temporal pupil decentration, pupil-centered ablation seemed to produce a lower amount of coma and, as a consequence, a reduced loss of BCVA compared with vertex-centered patients.

Descemet stripping automated endothelial keratoplasty in a child with descemet membrane breaks after forceps delivery.

PURPOSE: To report the use of Descemet stripping automated endothelial keratoplasty (DSAEK) and to treat visual loss in Descemet membrane (DM) breaks after forceps delivery. METHODS: An 8-year-old boy presented with unilateral DM ruptures secondary to forceps delivery. Central, vertically oriented DM breaks significantly decreased visual acuity. Preoperative visual acuity was 20/80. A DSAEK was performed, the DM and endothelium were stripped from the recipient, and an 8.5-mm-diameter donor button consisting of posterior stroma and healthy endothelium was folded and implanted through a 5-mm incision. An air bubble was used to press the donor tissue against the recipient cornea, allowing it to attach without sutures. RESULTS: Graft dislocation in the early postoperative period required surgical repositioning of the donor lenticule, which led to excellent anatomic and functional outcomes. There was a significant and rapid improvement of the best-corrected visual acuity, which was 20/50 at the first month and 20/32 at the seventh month postoperatively. CONCLUSIONS: To our knowledge, this is the first report of a DSAEK in a child with DM tears after forceps delivery. Selective replacement of posterior corneal layers with DSAEK might be a promising alternative to penetrating keratoplasty to successfully treat endothelial or DM lesions during childhood.

Fixed dilated pupil (urrets-zavalia syndrome) and anterior subcapsular cataract formation after descemet stripping endothelial keratoplasty.

PURPOSE: To report a fixed dilated pupil and anterior subcapsular cataract formation following Descemet stripping endothelial keratoplasty (DSAEK). METHODS: A 47-year-old man with Fuchs endothelial dystrophy underwent DSAEK of the right eye. The preoperative slit lamp examination was normal. Mydriatic drops were used at the end of procedure. RESULTS: Postoperatively, the pupil remained fixed and dilated with no right direct or consensual response to light, or constriction during accommodation throughout a 1-year follow-up period. Slit lamp examination after air resorption revealed a transient anterior subcapsular cataract and posterior synechiae. Based on these findings, a diagnosis of Urrets-Zavalia syndrome was made. CONCLUSION: To our knowledge, this is the first report of Urrets-Zavalia syndrome after DSAEK.

Esotropias that totally resolve under general anesthesia treated exclusively with bilateral fadenoperation.

PURPOSE: Fadenoperation has been proven to be an efficient method to treat convergence excess because it treats medial rectus (MR) overaction. We wanted to evaluate its efficiency in esotropias that totally disappear under anesthesia, regardless of the amount of deviation in waking hours. METHODS: Included were 122 successive cases of children of ages 3 to 16 years with esotropia that completely disappears under general anesthesia (GA), representing 26.25% of all patients with esotropia that had surgery between August 2002 and July 2004. They all received a fadenoperation (retroequatorial strapping) of both MR without recession with a 5/0 nylon suture. RESULTS: Patients were evaluated between 27 and 51 months postoperatively. Mean initial deviation was 21 prism dioptres (PD) at distance and 31 PD at near fixation. Of the 122 cases, 102 (83.6%) showed stable postoperative deviation between +8 and -8 PD, 7 showed exotropias (< 20 PD), and 13 showed esotropias (< 20 PD). These results were found without correlation to preoperative angle of deviation, ametropia, age at surgery, or association with vertical surgery. CONCLUSION: Our results suggest that fadenoperation of MR is an option to treat esotropias that disappear under anesthesia. The retroequatorial strapping we use seems safer than classical fadenoperation. We believe that the position of the eyes under GA should be considered for the surgical approach of esotropias.