Primary cilia formation requires the Leigh syndrome-associated mitochondrial protein NDUFAF2.

Mitochondria-related neurodegenerative diseases have been implicated in the disruption of primary cilia function. Mutation in an intrinsic mitochondrial complex I component NDUFAF2 has been identified in Leigh syndrome, a severe inherited mitochondriopathy. Mutations in ARMC9, which encodes a basal body protein, cause Joubert syndrome, a ciliopathy with defects in the brain, kidney, and eye. Here, we report a mechanistic link between mitochondria metabolism and primary cilia signaling. We discovered that loss of NDUFAF2 caused both mitochondrial and ciliary defects in vitro and in vivo and identified NDUFAF2 as a binding partner for ARMC9. We also found that NDUFAF2 was both necessary and sufficient for cilia formation and that exogenous expression of NDUFAF2 rescued the ciliary and mitochondrial defects observed in cells from patients with known ARMC9 deficiency. NAD+ supplementation restored mitochondrial and ciliary dysfunction in ARMC9-deficient cells and zebrafish and ameliorated the ocular motility and motor deficits of a patient with ARMC9 deficiency. The present results provide a compelling mechanistic link, supported by evidence from human studies, between primary cilia and mitochondrial signaling. Importantly, our findings have significant implications for the development of therapeutic approaches targeting ciliopathies.

Temperature Elevation in the Human Eye Due To Intraocular Projection Prosthesis Device.

Corneal opacity is a leading cause of blindness worldwide. Corneal transplantation and keratoprosthesis can restore vision but have limitations due to the shortage of donor corneas and complications due to infection. A proposed alternative treatment using an intraocular projection prosthesis device can treat corneal disease. In this study, we perform a transient thermal analysis of the bionic eye model to determine the power the device can produce without elevating the eye tissue temperature above the 2°C limit imposed by the international standard for implantable devices. A 3D finite element model, including blood perfusion and natural convection fluid flow of the eye, was created. The device was placed 1.95 mm from the iris, which experienced less than 2°C rise in the tissue temperature at a maximum power dissipation of LED at 100 mW and microdisplay at 25 mW.

Characterization of an Electronic Corneal Prosthesis System.

PURPOSE: Corneal opacity is a leading cause of reversible blindness worldwide. An electronic corneal prosthesis, or intraocular projector, could potentially restore high-quality vision without need for corneal clarity. MATERIALS AND METHODS: Four intraocular projection systems were constructed from commercially available electronic components and encased in biocompatible plastic housing. They were tested for optical properties, biocompatibility, heat dissipation, waterproofing, and accelerated wear. A surgical implantation technique was developed. RESULTS: Intraocular projectors were produced of a size that can fit within the eye. Their optics produce better than 20/200 equivalent visual acuity. MTT assay demonstrated no cytotoxicity of devices in vitro. Temperature testing demonstrated less than 2°C increase in temperature after 1 h. Three devices lasted over 12 weeks under accelerated wear conditions. Implantation surgery was demonstrated via corneal trephination insertion in a cadaver eye. CONCLUSION: This is the first study to demonstrate and characterize fully functional intraocular projection systems. This technology has the potential to be an important new tool in the treatment of intractable corneal blindness.

Late detachment of Descemet's membrane after penetrating keratoplasty for pellucid marginal degeneration.

PURPOSE: we report a case of late spontaneous large detachment of Descemet's membrane in recurrent pellucid marginal degeneration after penetrating keratoplasty. OBSERVATIONS: a 73-year-old man presented to clinic with spontaneous detachment of his Descemet's membrane 30 years after penetrating keratoplasty for pellucid marginal degeneration. Efforts were made to bubble the membrane back into place without success. The patient then underwent endothelial keratoplasty with successful restoration of cornea clarity. CONCLUSIONS AND IMPORTANCE: this condition may cause diagnostic and treatment dilemmas if not properly identified and managed. In addition this case has information for both the use of scleral contact lens and the success of endothelial keratoplasty in an extremely steep cornea.

Feasibility of Intraocular Projection for Treatment of Intractable Corneal Opacity.

Despite many decades of research and development, corneal opacity remains a leading cause of reversible blindness worldwide. Corneal transplantation and keratoprosthesis can restore corneal clarity, but both have well-known limitations. High-resolution electronic microdisplays may offer an alternative to traditional methods of treating corneal disease using an intraocular implant to project imagery onto the retina, obviating the need for a clear cornea. In this study, we review previous work and recent technologic developments relevant to the development of such an intraocular projection system.

3D printing for low cost, rapid prototyping of eyelid crutches.

Blepharoptosis or ptosis is a common and potentially debilitating clinical problem. Long-term surgical treatment for ptosis caused by progressive myopathies can be challenging due to potential recurrence and complications associated with facial muscle weakness. When surgical treatment is no longer effective, an eyelid crutch can be used as an alternative intervention. This report demonstrates how 3D printing was used to rapidly design, prototype, and manufacture new custom-fit eyelid crutches at a low cost.

Iris suture fixation: Push-knot needle.

We describe a technique to create a locking knot for iris reconstruction or intraocular lens fixation. A modified needle is prepared by straightening the tip of an ophthalmic viscosurgical device needle or a lacrimal cannula needle. After the suture is passed through 2 sides of an iris defect, the 2 ends are externalized and looped. One strand is then inserted into the needle from the tip out of the ferrule, and the knot is pushed into the anterior chamber by this needle in a controllable manner. Two other locking knots are then made by repeating the process. With this method, only 1 small corneal incision is necessary regardless of the number of knots required and only a small amount of anterior chamber space is needed during the knotting process.

Subjective Quality of Vision After Myopic LASIK: Prospective 1-Year Comparison of Two Wavefront-Guided Excimer Lasers.

PURPOSE: To compare subjective quality of vision between two wavefront-guided lasers in the treatment of myopia up to 1 year postoperatively. METHODS: In this prospective randomized study, 100 eyes of 50 patients were treated with wavefront-guided LASIK. One eye was treated with the WaveLight Allegretto Wave Eye-Q 400-Hz excimer laser (Alcon Laboratories, Inc., Hünenberg, Switzerland) and the other was treated with the VISX Star S4 IR CustomVue excimer laser (Abbott Medical Optics, Santa Ana, CA). Patients completed a questionnaire assessing quality of vision and visual symptoms preoperatively and at postoperative months 1, 3, 6, and 12. RESULTS: The Allegretto system demonstrated non-statistically significant superiority in several subjective parameters as early as 1 month after surgery. At 12 months, there was better clarity during the day (P = .001) in the Allegretto group. Subgroup analyses were performed on eyes with preoperative higher order aberrations of 0.3 µm or less and in patients with preoperative higher order aberrations greater than 0.3 µm. In subgroup analysis, there were no differences between the two systems in eyes with low higher order aberrations or high higher order aberrations. Patients did not express any preference for one system over the other when surveyed at 1 year postoperatively. CONCLUSIONS: One year after surgery, there were no differences in self-reported quality of vision outcomes with the exception of better clarity of vision during the day in the eyes treated with the Allegretto system. Patients did not express any preference for one treatment modality over the other.

Comparison of 2 femtosecond lasers for flap creation in myopic laser in situ keratomileusis: one-year results.

PURPOSE: To compare laser in situ keratomileusis (LASIK) outcomes between 2 femtosecond lasers for flap creation in the treatment of myopia up to 1 year. SETTING: University eye clinic. DESIGN: Prospective randomized eye-to-eye study. METHODS: Consecutive myopic patients were treated with wavefront-guided LASIK. One eye had a flap created by the Intralase FS 60 kHz femtosecond laser, and the fellow eye was treated with the Intralase iFS 150 kHz femtosecond laser. Eyes were randomized according to ocular dominance. Evaluations included measurement of uncorrected distance visual acuity (UDVA), corrected distance visual acuity, contrast sensitivity and wavefront aberrometry. RESULTS: The study enrolled 122 eyes of 61 patients. The mean preoperative spherical equivalent refraction was -4.62 diopters (D) ± 2.32 (SD) and -4.66 ± 2.30 D in the 150 kHz group and 60 kHz group, respectively. Patients preferred the 150 kHz laser to the 60 kHz laser intraoperatively (52.5% versus 26.2%) (P = .005). One week postoperatively, UDVA was 20/16 or better in 85.2% in the 150 kHz group and 70.5% in the 60 kHz group; the difference was statistically significant (P < .05). At 12 months, there were no significant differences in refractive outcomes or higher-order aberrations between the 2 groups. CONCLUSIONS: Flap creation with the 150 kHz system and the 60 kHz system resulted in excellent LASIK outcomes. Intraoperatively, patients preferred the 150 kHz system, which yielded better UDVA in the early postoperative period. There were no significant differences at 1 year between the 2 laser systems. FINANCIAL DISCLOSURE: Proprietary or commercial disclosures are listed after the references.

Day 1 wavefront aberrometry for prediction of refractive outcomes at year 1 in myopic LASIK.

PURPOSE: To determine amount of change in wavefront aberrometric measurements from 1 day to 1 year after myopic LASIK. METHODS: One hundred five eyes of 105 patients underwent wavefront-guided LASIK. Objective wavefront aberrometric refractions were recorded preoperatively, at postoperative day 1, and at postoperative year 1. Subjective manifest refractions were also collected at postoperative year 1. RESULTS: When comparing objective wavefront aberrometric refractions at postoperative year 1 to postoperative day 1, there was a mean 0.33 diopter spherical equivalent myopic shift. There was no significant difference in the number of eyes within 1.00 diopter of emmetropia spherical equivalent measured by wavefront aberrometric refraction at postoperative day 1 or year 1. There was a correlation of R(2) = 0.14 between degree of preoperative myopia and myopic shift. Higher-order aberrations were overall not increased at day 1 but increased significantly by year 1. Objective aberrometric refractions at postoperative day 1 can be useful in prediction of long-term refractive outcomes. CONCLUSIONS: There is a small myopic shift and an increase in higher-order aberrations when comparing wavefront aberrometry results at postoperative day 1 with those at postoperative 1 year.

Biocompatibility of poly(ethylene glycol) and poly(acrylic acid) interpenetrating network hydrogel by intrastromal implantation in rabbit cornea.

We evaluated the biocompatibility of a poly(ethylene glycol) and poly(acrylic acid) (PEG/PAA) interpenetrating network hydrogel designed for artificial cornea in a rabbit model. PEG/PAA hydrogel measuring 6 mm in diameter was implanted in the corneal stroma of twelve rabbits. Stromal flaps were created with a microkeratome. Randomly, six rabbits were assigned to bear the implant for 2 months, two rabbits for 6 months, two rabbits for 9 months, one rabbit for 12 months, and one rabbit for 16 months. Rabbits were evaluated monthly. After the assigned period, eyes were enucleated, and corneas were processed for histology and immunohistochemistry. There were clear corneas in three of six rabbits that had implantation of hydrogel for 2 months. In the six rabbits with implant for 6 months or longer, the corneas remained clear in four. There was a high rate of epithelial defect and corneal thinning in these six rabbits. One planned 9-month rabbit developed extrusion of implant at 4 months. The cornea remained clear in the 16-month rabbit but histology revealed epithelial in-growth. Intrastromal implantation of PEG/PAA resulted in a high rate of long-term complications.

Successful DMEK after intraoperative graft inversion.

PURPOSE: Hardiness of a Descemet membrane endothelial keratoplasty (DMEK) graft is not well established. The aim of this study was to report a case of graft survival after intraoperative inversion. METHODS: We describe a case of a 76-year-old man with Fuchs corneal dystrophy who underwent DMEK in the left eye. After deployment of the graft and a 15-minute sulfur hexafluoride gas fill, the graft was noted to be inverted. The graft was then reoriented and properly positioned. RESULTS: Because of progressive graft detachment, rebubble was required at 2 weeks after surgery. At 2 months after surgery, the graft was clear and fully adherent. Specular microscopy revealed 27.9% endothelial cell loss of the donor cornea. CONCLUSIONS: Despite intraoperative inversion, this DMEK graft remained viable without excessive endothelial cell loss.

A comparison of LASIK flap thickness and morphology between the Intralase 60- and 150-kHz femtosecond lasers.

PURPOSE: To prospectively compare the achieved thickness and consistency of LASIK flaps created with a 60- and 150-kHz femtosecond laser. METHODS: One hundred twenty eyes of 60 patients with myopia were treated with LASIK. One eye had flap created by the Intralase FS 60-kHz femtosecond laser (Abbott Medical Optics, Abbott Park, IL) and the fellow eye was treated with the IntraLase iFS 150-kHz femtosecond laser (Abbott Medical Optics). Eyes were randomized according to ocular dominance. Flap morphology and measurements were taken with anterior segment optical coherence tomography (AS-OCT) at the 1-month postoperative visit. RESULTS: AS-OCT showed similar regular planar morphologies in both groups. The mean thickness of the flaps in the FS 60 group was significantly higher than that of the iFS 150 group (105.4 ± 3.9 µm vs 103.9 ± 4.8 µm, P = .009). The mean deviation from targeted flap thickness was not significantly different between the two groups. CONCLUSIONS: The Intralase iFS 150-kHz femtosecond laser creates flaps of similar thickness and uniformity to the Intralase FS 60-kHz femtosecond laser.

Prevention and treatment of injection-related endophthalmitis.

BACKGROUND: Intravitreal injections are the fastest growing cause of endophthalmitis and can result in severe vision loss. The prevention, diagnosis and management of such infections remain unclear and at times controversial. METHODS: We searched Pubmed for keywords "prophylaxis," "endophthalmitis," "intravitreal injection." We focused on studies published in the last 2 years as well as other recent studies with particular attention to data on the incidence, microbiology, prevention, and treatment of injection-related endophthalmitis. RESULTS: Over 20 relevant studies were found. With povidone-iodine preparation, the per-injection endophthalmitis rate is low at about 0.03%. Antibiotics do not appear to be beneficial for prevention of post-injection endophthalmitis. The best timing of vitrectomy is unclear. CONCLUSIONS: Antibiotic prophylaxis is probably not needed when giving intravitreal injections. More data is needed to help determine the proper treatment for post-injection endophthalmitis.

Comparison of 2 wavefront-guided excimer lasers for myopic laser in situ keratomileusis: one-year results.

PURPOSE: To compare laser in situ keratomileusis (LASIK) outcomes between 2 wavefront-guided excimer laser systems in the treatment of myopia. SETTING: University eye clinic, Palo Alto, California, USA. DESIGN: Prospective comparative case series. METHODS: One eye of patients was treated with the Allegretto Wave Eye-Q system (small-spot scanning laser) and the fellow eye with the Visx Star Customvue S4 IR system (variable-spot scanning laser). Evaluations included measurement of uncorrected visual acuity, corrected visual acuity, and wavefront aberrometry. RESULTS: One hundred eyes (50 patients) were treated. The mean preoperative spherical equivalent (SE) refraction was -3.89 diopters (D) ± 1.67 (SD) and -4.18 ± 1.73 D in the small-spot scanning laser group and variable-spot scanning laser group, respectively. There were no significant differences in preoperative higher-order aberrations (HOAs) between the groups. Twelve months postoperatively, all eyes in the small-spot scanning laser group and 92% in the variable-spot scanning laser group were within ±0.50 D of the intended correction (P = .04). At that time, the small-spot scanning laser group had significantly less spherical aberration (0.12 versus 0.15) (P = .04) and significantly less mean total higher-order root mean square (0.33 µm versus 0.40 µm) (P = .01). Subjectively, patients reported that the clarity of night and day vision was significantly better in the eye treated with the small-spot scanning laser. CONCLUSIONS: The predictability and self-reported clarity of vision of wavefront-guided LASIK were better with the small-spot scanning laser. Eyes treated with the small-spot scanning laser had significantly fewer HOAs.

Prevention of postcataract endophthalmitis: evidence-based medicine.

PURPOSE OF REVIEW: To provide a summary of current peer-reviewed publications on the methods of prophylaxis against postcataract endophthalmitis. RECENT FINDINGS: Preoperative application of povidone-iodine remains the standard protocol for the prevention of postoperative endophthalmitis. More recent evidence suggests that intracameral cefuroxime administered at the conclusion of surgery significantly reduces the risk of endophthalmitis. However, its clinical use has been limited because of a lack of commercially available antibiotic indicated for intraocular injection. Although topical antibiotic application continues to be a controversial topic with respect to the types of antibiotic prescribed and dosage, most ophthalmologists do prescribe an antibiotic for the perioperative period. Resistance against antibiotics, including the very popular classes of fluoroquinolones, is rising. Most notably, methicillin resistance continues to increase over time. SUMMARY: Prevention of postcataract endophthalmitis remains a difficult topic to study given the low incidence. In addition to appropriate wound construction, a combination of povidone-iodine and antibiotics provide a reasonable approach in reducing the risk of this rare but serious infection.

Vascular endothelial growth factor mediates corneal nerve repair.

PURPOSE: To examine the expression of vascular endothelial growth factor (VEGF) and its receptors in the cornea and the trigeminal ganglion and to characterize the role of VEGF in mediating corneal nerve repair. METHODS: Regeneration of the corneal subbasal nerve plexus after epithelial debridement was measured. The expression of VEGF and its receptors was examined in the trigeminal ganglia and in the cornea by RT-PCR, immunohistochemistry, and Western blotting. VEGF-mediated nerve growth was measured in a trigeminal ganglia explant assay. Anti-VEGF neutralizing antibody was used to examine the VEGF-dependent growth of neurons in vitro and regeneration of the corneal nerves in vivo. RESULTS: After two distinct patterns of nerve regeneration, the subbasal nerves recovered to 65% of the preinjury density after 28 days. RT-PCR demonstrated gene expression of VEGF and VEGF receptors in the trigeminal ganglia. Immunohistochemistry showed staining for VEGF and its receptors in the trigeminal ganglia and for VEGFR1, VEGFR2, and neuropilin (NRP)-1 in the cornea. Western blot confirmed these results. In vitro, VEGF promoted the growth of explanted trigeminal ganglia by 91%. Blockage of VEGF signaling with anti-VEGF antibody reduced the growth of cultured neurons by 17% and the regeneration of subbasal neurons by 23%. CONCLUSIONS: In addition to providing new information on the regeneration of murine corneal nerves, this study presents evidence that VEGF signaling influences the repair of corneal nerves by demonstrating that VEGF and VEGF receptors are present in the trigeminal ganglia and that abrogation of VEGF signaling reduces nerve growth in vitro and in vivo.

Transgenic corneal neurofluorescence in mice: a new model for in vivo investigation of nerve structure and regeneration.

PURPOSE: To quantify the level of neuron-specific fluorescence in the corneas of transgenic mice expressing yellow fluorescent protein (YFP) driven by the thy1 promoter and examine the viability of using thy1-YFP mice as a model for studying nerve regeneration in vivo. METHODS: The structure of corneal innervation in thy1-YFP mice visible with reporter gene fluorescence was compared with that visible with traditional immunofluorescence techniques. The percentage of corneal nerves with YFP fluorescence in wholemounted corneas and trigeminal neuron cultures was determined. Regeneration of fluorescent corneal neuronal processes after wounding was monitored in vivo. RESULTS: In the mouse cornea, neuron-specific immunostaining determined that nerves enter the stroma in several bundles that then extend throughout the entire cornea. These stromal nerve bundles form a subbasal plexus beneath the corneal epithelium. Fine nerves from this plexus travel superficially to the ocular surface. Neuron-specific expression of YFP allowed visualization of nearly all large nerve bundles of the stroma but only some of the many finer nerves of the subbasal plexus and surface. In the subbasal nerve plexus, 46% of total neuronal processes exhibited YFP neurofluorescence. In vitro, 22% of cultured trigeminal neurons exhibited YFP neurofluorescence. After corneal nerve transection, nerve processes distal to the site of injury degenerated, whereas those proximal to the site regenerated in a pattern different from original nerve architecture. CONCLUSIONS: Thy1-YFP mice display neurofluorescence and provide a novel model for monitoring the patterning, injury, and growth of corneal nerves in vivo.