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Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Competing Interests: The authors declare that they have no conflict of interest.

Background: The aim of our study was to evaluate the clinical outcomes after Keraring implantation for keratoconus in patients with thin corneas., Patients and Methods: Ten eyes from 10 patients with keratoconus, who underwent femtosecond laser-assisted Keraring implantation for keratoconus, were included in this retrospective study. Uncorrected visual acuity (UCVA), corrected visual acuity (CDVA), keratometric readings, central corneal thickness and thinnest corneal pachymetry have been evaluated preoperatively and 6 months after the Keraring implantation., Results: UCVA, BCVA and keratometric readings improved at 6 months postoperatively., Conclusions: Our data showed significant keratometric amelioration and visual improvement after Keraring implantation for keratoconus in patients with thin corneas at 6 months postoperatively., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Importance: Cataract is associated with a progressive decline in light transmission due to the clouding and yellowing of the natural crystalline lens. While the downstream effects of aging lenses include long-term disruption of circadian rhythms, cognitive function, and sleep regulation, it remains unknown whether there is an association of intraocular cataract lens (IOLs) replacement with circadian rhythms, cognition, and sleep., Objective: To test whether IOL replacement (blue blocking [BB] or ultraviolet [UV] only blocking) in older patients with previous cataract is associated with the beneficial light effects on the circadian system, cognition, and sleep regulation., Design, Setting, and Participants: Cross-sectional study at the Centre for Chronobiology, University of Basel in Switzerland from February 2012 to April 2014, analyzed between June 2012 and September 2018. Sixteen healthy older controls and 13 patients with previous cataract and IOL replacement participated without medication and no medical and sleep comorbidities., Exposures: Three and a half hours of prior light control (dim-dark adaptation), followed by 2 hours of evening blue-enriched (6500 K) or non-blue-enriched light exposure (3000 K and 2500 K), 30 minutes in dim post-light exposure, 8 hours of sleep opportunity, and 2 hours of morning dim light following sleep., Main Outcomes and Measures: Salivary melatonin, cognitive tests, and sleep structure and electroencephalographic activity to test the association of IOLs with markers of circadian rhythmicity, cognitive performance, and sleep regulation, respectively., Results: The participants included 16 healthy older controls with a mean (standard error of the mean [SEM]) of 63.6 (5.6) years; 8 women and 13 patients with previous cataract (mean [SEM] age, 69.9 [5.2] years; 10 women); 5 patients had UV IOLs and 8 had BB IOLs. Patients with previous cataract and IOLs had an attenuated increase in melatonin levels during light exposure (mean [SEM] increase in the BB group: 23.3% [2.6%] and in the UV lens group: 19.1% [2.1%]) than controls (mean [SEM] increase, 48.8% [5.2%]) (difference between means, 27.7; 95% CI, 15.4%-41.7%; P < .001). Cognitive function, indexed by sustained attention performance, was improved in patients with UV lens (mean [SEM], 276.9 [11.1] milliseconds) compared with patients with BB lens (mean [SEM], 348.3 [17.8] milliseconds) (difference between means, 71.4; 95% CI, 29.5%-113.1%; P = .002) during light exposure and in the morning after sleep. Patients with UV lens had increased slow-wave sleep (mean [SEM] increase, 13% [3.4%]) compared with controls (mean [SEM] increase, 5.2% [0.8%]) (percentage of total sleep time; difference between means, 7.9; 95% CI, 2.4%-13.4%; P = .02) and frontal non-rapid eye movement slow-wave activity (0.75-4.5 Hz) during the first sleep cycle (mean [SEM], 79.9 [13.6] μV2/Hz) compared with patients with BB lens (mean [SEM], 53.2 [10.7] μV2/Hz) (difference between means, 26.7; 95% CI, 9.2-48.9; P = .03)., Conclusions and Relevance: These in-laboratory empirical findings suggest that optimizing the spectral lens transmission in patients with previous cataract may minimize the adverse age-related effects on circadian rhythms, cognition, and sleep.

Targeting genes to specific neuronal or glial cell types is valuable for both understanding and repairing brain circuits. Adeno-associated viruses (AAVs) are frequently used for gene delivery, but targeting expression to specific cell types is an unsolved problem. We created a library of 230 AAVs, each with a different synthetic promoter designed using four independent strategies. We show that a number of these AAVs specifically target expression to neuronal and glial cell types in the mouse and non-human primate retina in vivo and in the human retina in vitro. We demonstrate applications for recording and stimulation, as well as the intersectional and combinatorial labeling of cell types. These resources and approaches allow economic, fast and efficient cell-type targeting in a variety of species, both for fundamental science and for gene therapy.

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Capsulorhexis is one of the most important steps in cataract surgery. Good centration, circular overlap in sufficient size and a circular edge without tears result in good centration of the intraocular lens (IOL). In this study, the capsulorhexis results of an experienced surgeon are compared with reported data in femtolaser assisted cataract surgery (FLACS)., Patients and Methods: 105 consecutive operations were photographically documented; in 81 cases size and overlap were analysed retrospectively. The surgeon's personal anterior capsular tear rate was taken from the EUREQUO database., Results: Average rhexis size was 5.03 ± 0.3 mm; the difference between the two measured diameters was 0.28 ± 0.18 mm. Circular overlap was found in 88.9% of cases. No radial tears were observed in 8000 operations in EUREQUO, resulting in a rate of less than 0.0125% in manual surgery., Conclusions: The overlap rate of manual surgery was comparable to FLACS; whether the slightly 'rounder' capsulotomy is clinically relevant remains unclear. The risk of an anterior capsular tear is very low in the hands of an experienced surgeon and even lower than with FLACS., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Dacryocystography is a radiological procedure for the examination and localisation of obstructions of the lacrimal ducts, the findings of which are decisive for the choice between conservative or invasive surgical measures and thus for treatment planning.

Background: To report the natural, longitudinal history of shifts in refractive errors in different age groups in a large western European cohort over at least 5 years in the same patients., Methods: The electronic database of a large regional clinic containing 225,000 patients was searched for records of patients with a follow-up of at least 5 years, excluding all patients who had received any surgical interventions in any eye. This search retrieved 15,799 patients aged 3 months to 79 years (median 37.8 years) with refractive follow up of at least 5 years (mean 8.8 years) and no surgical interventions. Differences in spherical equivalents (sum of sphere +1/2 cylinder) and cylinder between first and last visit in the same patients in only the right eye were calculated, and used as the measure of refractive shift. Subsequently differences in change between the right and left eye were also determined., Results: Refractions were found to be mostly stable from 25 to 39 years (n = 3,155 right eyes), with 50% of these patients not changing their refraction. In patients aged 20-24 (n = 825 right eyes), only 39% of the refractions remained stable, whereas 49% experienced a myopic shift. In the age group 40-69 years (n = 6,694), 40-45% remained stable, with an increase in hyperopic shifts. Eighty-five percent of all patients had bilateral symmetric shifts, and 61% showed stable cylindrical values., Conclusions: This report documents clinical relevant changes in spherical equivalents in all age groups within 5 to 10 years in the largest examined European cohort. Refractive surgery patients in particular should be selected accordingly, and be informed about the physiological changes which might still occur during their lifetime.

We report on the first implanted Osteo-Odonto-Keratoprosthesis (OOKP) in Switzerland. The procedure is only performed in cases of severe bilateral corneal vision impairment without alternatives (e. g. allogenic corneal transplant). At this two-staged surgery a single-rooted tooth is removed with its belonging bone and an optic cylinder is centrally inserted. This tooth-bone-optic-cylinder-complex is implanted temporarily submuscular in the infraorbital area. Oral mucosa is removed and transplanted on to the eye. Three months later the complex is removed, the oral mucosa partially detached, the underlying cornea perforated, the lens, iris and anterior vitreous body removed and the tooth-optic-zylinder-complex fixated on the globe. After this procedure, our patient has a best corrected visual acuity of 0,7.

A problem in cataract surgery consists in the preoperative identification of the appropriate intraocular lens (IOL) power. Different calculation approaches have been developed for this purpose; raytracing methods represent one of the most exact but also mathematically more challenging methods. This article gives a systematic overview of the different raytracing calculations available and described in the literature and compares their results. It has been shown that raytracing includes physical measurements and IOL manufacturing data but no approximations. The prediction error is close to zero and an essential advantage is the applicability to different conditions without the need of modifications. Compared to the classical formulae the raytracing methods are more precise overall, but due to the various data and property situations they are hardly comparable yet. The raytracing calculations represent a good alternative to the 3rd generation formulae. They minimize refractive errors, are wider applicable and provide better results overall, particularly in eyes with preconditions., (Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: To evaluate a new high-resolution noncontact biometer (Lenstar; Haag-Streit AG, Koeniz, Switzerland) using optical low-coherence reflectometry and to compare the clinical measurements with those obtained from the IOLMaster (Carl Zeiss, Jena, Germany) and the Pachmumeter (Haag-Streit AG)., Design: Exploratory evaluation of diagnostic technology and nonrandomized, prospective clinical trial., Participants: Eighty subjects (144 eyes) aged 20 to 90 years with cataractous, pseudophakic, aphakic, silicon oil-filled, or normal eyes., Methods: Measurements of axial length (AL), anterior chamber depth (ACD), central corneal thickness (CCT), corneal radius (R1 [flattest radius of corneal curvature] and R2 [steep radius, 90 degrees apart from R1]), and axis of the flattest radius (Ax1) obtained with the Lenstar were compared with those obtained with the IOLMaster or Pachmumeter. The results were evaluated using Bland-Altman analyses. The differences between both methods were assessed using the paired t test, and its correlation was evaluated by Pearson coefficient., Main Outcome Measures: Axial length, CCT, ACD, R1, R2, and Ax1., Results: The overall mean AL measured with the Lenstar and the IOLMaster was 24.1 mm (r = 0.999). Anterior chamber depth was 3.19 mm (Lenstar) and 3.17 mm (IOLMaster; r = 0.875). Excellent correlations also were found for the corneal radius and the axis of flattest radius (R1, r = 0.927; R2, r = 0.929; and Ax1, r = 0.938). Mean CCT was 0.557 mm (r = 0.978) for both Lenstar and Pachmumeter., Conclusions: Measurements with the new Lenstar correlated well with those with the IOLMaster and Pachmumeter in cataractous, pseudophakic, aphakic, silicon oil-filled, and normal eyes. It is an accurate, fast instrument that provides additional information of interest to any cataract or refractive surgeon.

Aims: GS-101 (GeneSignal, Epalinges, Switzerland) is an antisense oligonucleotide that inhibits the expression of the scaffold protein insulin receptor substrate-1 (IRS-1). Inhibition of IRS-1 results in the prevention of neovascular growth and was shown to prevent the angiogenic process in preclinical in vitro and in vivo experiments. There is therefore a strong therapeutic rational for targeting angiogenesis in pathological neovascularization. We aimed to investigate the safety, tolerability and bioavailability of GS-101 eye drops., Methods: This was a Phase I open-label study. The investigation was performed in two steps. Local ocular tolerability was first assessed with the application of one single low dose in one eye. After no signs of intolerance were observed in the subjects, the dose escalation phase of the study was initiated, and the remaining subjects received three times daily escalating doses of GS-101 in one eye for 14 days., Results: The 14 healthy volunteers tolerated well 14 days' continued use of escalating doses of GS-101 from 43 to 430 microg per day. Other than itching, experienced also in the control eye by one subject and determined to be unrelated to the study treatment, no signs of intolerance were observed., Conclusions: The tolerability profile obtained from this study suggests that GS-101 is safe for human use. Further clinical evaluations in diseases related to abnormal angiogenesis are being targeted. In particular, the neovascularization-related orphan indications of corneal graft rejection, retinopathy of pre-maturity and neovascular glaucoma are currently under Phase II clinical investigation and are showing promising results.

Purpose: Evidence suggests that altered metabolism of amyloid precursor protein (APP) may play a role in the pathophysiology of retinal ganglion cell (RGC) death in the etiology of glaucoma. The authors sought to determine the distribution of APP and amyloid-beta (Abeta) in DBA/2J glaucomatous mouse retinas., Methods: The retinas of 3- and 15-month-old DBA/2J mice and C57/BL-6 mice (control group) were fixed with 4% paraformaldehyde and processed for immunohistochemistry. Antibodies used included a polyclonal antibody to the C terminus of Abeta 40 and a polyclonal antibody to the APP ectodomain. Immunohistochemically stained tissue was graded using light microscopy. Distribution and semiquantitative expression of APP and Abeta in young and old glaucomatous and normal retinas were determined and compared., Results: Strong APP and Abeta immunoreactivity was found in the RGC layer, optic nerve, and pia/dura of old DBA/2J retinas, with considerably higher intensity found in the old compared with the young DBA/2J mice. In contrast to glaucomatous mice, the control group did not show any notable age-related difference., Conclusions: Disruption of the homeostatic properties of secreted APP with consecutive Abeta cytotoxicity might be a contributing factor of ganglion cell loss in glaucomatous mouse retinas.

Background: Little is known about the ocular penetration of echinocandin antifungals. We studied the ocular distribution of systemically administered caspofungin in a rabbit uveitis model., Methods: Caspofungin (1 mg/kg per day) was given intravenously to rabbits as a single dose or as repeated daily doses on 7 days starting 24 h after induction of unilateral uveitis by intravitreal endotoxin injection. Caspofungin concentrations were determined by high-performance liquid chromatography in the cornea, aqueous humor, vitreous humor, and serum 4, 8, 16, and 24 h after administration of a single dose and 24 h after the last of seven doses., Results: The mean caspofungin concentration in the aqueous of the inflamed eye 4 and 8 h after single-dose administration was 1.30 +/- 0.39 microg/ml and 1.12 +/- 0.34 microg/ml, respectively. Drug concentrations decreased to 0.24 +/- 0.09 microg/ml at 16 h and 0.26 +/- 0.14 microg/ml at 24 h. In the vitreous of inflamed eyes drug levels were undetectable at all time points. No drug was found in the aqueous of inflamed eyes 24 h after the last of seven repeated doses, and the vitreous only contained trace amounts. In the corneas of inflamed eyes concentrations reached 1.64 +/- 0.48 microg/g at 4 h, peaked at 2.16 +/- 1.14 microg/g at 8 h, and declined to 1.87 +/- 0.52 microg/g and 1.49 +/- 0.48 microg/g at 16 and 24 h, respectively. After repeated dosing, corneal concentrations of caspofungin were 0.8 and 1.0 microg/g and below the limit of detection in two of four animals. In non-inflamed eyes no drug was detectable in the aqueous and vitreous humor, and the corneas at any time point., Conclusions: In our model, caspofungin reached therapeutically relevant levels in the aqueous and cornea but not in the vitreous humor of inflamed eyes. Intraocular drug deposition was critically dependent on a disrupted blood-eye barrier. These findings suggest a limited role for caspofungin in the treatment of fungal endophthalmitis.

Background: "Hornussen" is a traditional Swiss team game played in rural areas of Switzerland. A puck made out of hard plastic called "Hornuss" or "Nouss" is hit with a lash like racket into the field. The opposing team has to capture the flying puck with shovel like shields. Eye injuries are rare, however, very severe., Patients: We report on three patients who were seen and treated at the university eye clinic Berne in the last four years., Results: All injuries were blunt contusions with involvement of the periorbital soft tissues by a hit with the "Hornuss". In two cases orbital fractures were observed and in one case there was a rupture of the globe in a pre-injured aphakic eye. Only in one case was there a direct hit to the eye by the "Hornuss", the other injuries were caused by indirect hit after the "Hornuss" bounced off the shovel like shields. No protection gear was used. One patient showed complete recovery, whereas in the other two cases significant impairment remained., Conclusions: Without adequate protection gear, injuries caused by "Hornussen" are generally severe. The injury pattern with periorbital involvement resembles eye injuries caused by baseballs. This is probably due to the similar size of the balls. The mandatory wearing of protection helmets issued by the federal "Hornusser" association for young players should be extended as a general requirement for all players.

Background: Purpose of this retrospective study was to analyze outcome and complications after penetrating keratoplasty (PK) in patients with Down's syndrome., Patients and Methods: The medical records of all patients with Down's syndrome and PK from 1985 were reviewed retrospectively. Age, sex, systemic diseases, communication, indication for surgery and surgical technique, age at first PK, complications, visual acuity and best corrected visual acuity and findings at last follow-up were noted. Age matched mentally non-retarded patients with keratoconus and PK served as a control group., Results: All eyes of 9 patients had keratoconus, 16 were operated. Indication for surgery was spontaneous perforation in 3 and refractive in the remaining 13 eyes. Five grafts were clear at last follow-up. In 7 eyes, at least 1 re-PK had to be performed. Seven eyes developed graft rejection and 4 eyes needed conjunctival grafting because of non-healing epithelial defects. Ten eyes developed cataracts, 3 secondary glaucoma. In the control group 22 out of 25 operated corneas were clear at last follow-up., Conclusions: Prognosis of PK in patients with Down's syndrome is worse than in other patients with keratoconus. Poor results are not only explained due to the lack of cooperation of patients, but also because of: 1) high rate of emergency procedures (3/16), 2) presence of lid anomalies and 3) very advanced keratoconus, necessitating bigger sized grafts, leading to frequent immunological reactions, suture loosening and secondary glaucoma. Indication for PK in Down's syndrome patients with keratoconus and floppy eyelids should be very restrictive. Postoperative complications and the high rejection rate might be decreased by performing deep lamellar keratoplasty as this would not be an intraocular procedure.

Objective: To determine if patients with nonarteritic ischemic optic neuropathy (NAION) have sleep apnea syndrome (SAS), an entity characterized by repetitive upper airway obstructions during sleep, inducing hypoxia and sleep disruption., Methods: We recruited 17 patients with NAION and 17 age- and sex-matched controls from patients referred for treatment because of suspected restless legs syndrome. We performed overnight polysomnography and determined the respiratory disturbance index during night sleep, a value used to diagnose and grade SAS. We compared the proportions of patients with SAS among patients with NAION and matched controls using the chi(2) test. Additionally, we compared the proportions of patients with SAS among patients with NAION and a large SAS prevalence study using the binomial test., Results: Twelve (71%) of 17 patients with NAION had SAS. According to the respiratory disturbance index, 4 patients (24%) had mild, 4 patients (24%) had moderate, and 4 patients (24%) had severe SAS. Only 3 (18%) of 17 controls had SAS (P =.005). In the 45- to 64-year age group, 4 (50%) of 8 patients with NAION had SAS; 51 (11.9%) of 430 of the random sample in the prevalence study had SAS (P =.005). In the group older than 64 years, 8 (89%) of 9 patients with NAION had SAS; 18 (24%) of 75 of the random sample in the prevalence study had SAS (P<.001)., Conclusions: We found a high prevalence of SAS in patients with NAION, which supports previous case reports suggesting that such an association exists. This association may explain why approximately 75% of all patients with NAION discover visual loss on first awakening or when they first use vision critically after sleeping. Our findings indicate that SAS may play an important role in the pathogenesis of NAION.

Purpose: To determine the number and cytoarchitecture of retinal ganglion cells (RGCs) in the female Wistar rat, by using a newly devised procedure for rapid RGC counting in the entire retina that avoids assumptions about RGC spatial arrangement., Methods: RGCs of normal female Wistar rats were retrogradely labeled with a fluorescent tracer. Automated counting was accomplished by applying standard imaging software to analysis of all labeled cells in retinal flatmounts. The method was validated by comparison of automated and manual counts of 70,000 RGCs in frames covering the density range in the normal rat retina of 600 to 3600 RGC/mm(2). RGC numbers were determined for each retina and compared with the contralateral retina of the same animal. RGC density maps were constructed for each retina. RGC size distribution was determined., Results: Automated RGC counting showed a good linear correlation with manual counting (R(2) = 0.9416). Mean total RGC count in 10 rat eyes was 97,609 +/- 3,930 (SEM) per eye. Contralateral eyes differed by an average of 4.1% (3983 plus minus 5098 RGCs). Size analysis calculated from cell areas confirmed that the majority of rat RGCs are between 7 and 21.5 microm in equivalent diameter. The RGC counts for all frames at the same eccentricity in all 10 of the retinas showed that variability increased with eccentricity and increased further as the fractional area of the retina sampled at each eccentricity was reduced. There was also significant variability in the spatial density of the RGCs at the same eccentricity location between different eyes. Comparison of total RGC counts between left and right eyes estimated from RGC counts in sectors of the retina (hemiretinas or quadrants) showed increased variability compared with counting all the RGCs in a retina., Conclusions: RGCs in the Wistar rat display significant variability in their cytoarchitecture. Such variability can make quantification by sampling problematic for diffuse, and particularly, for focal RGC losses resulting from experimental interventions, unless virtually the entire RGC population is counted.