Femtosecond-Laser Assisted Deep Anterior Lamellar Keratoplasty (F-DALK)

DALK is a demanding procedure performed by comparably few surgeons. Femtosecond-laser assisted DALK (f-DALK) potentially shortens the learning curve for surgeons, which benefits patients by reducing the invasiveness of the procedure, improving the odds against complications and by maintaining patient’s own, healthy endothelial tissue. The key advantage in using the femtosecond laser for DALK is the higher rate of successful intraoperative preparation and thus, fewer conversions to penetrating keratoplasty

Bilateral corneal perforation in Ipilimumab/Nivolumab - associated peripheral ulcerative keratitis

Purpose: To present a case of immune checkpoint inhibitor-induced bilateral peripheral ulcerative keratitis that progressed to corneal perforation requiring keratoplasty in both eyes. Observations: We describe the course of a 60-year-old man treated with a combination of Ipilimumab and Nivolumab for metastatic melanoma who presented with foreign body sensation and epiphora in both eyes.Bilateral immune-related peripheral ulcerative keratitis was refractory to topical anti-inflammatory therapy, necessitating repetitive, but unsuccessful cyanoacrylate gluing procedure followed by bilateral lamellar mini-keratoplasty. Conclusions and importance: Combined immune checkpoint inhibition revokes the corneal immune privilege and can lead to auto-immune keratitis with recalcitrant progression to ulceration and perforation

Non-invasive quantification of corneal vascularization using anterior segment optical coherence tomography angiography

Abstract The presence of corneal vascularization (CV) interferes with the angiogenic and immune privilege of the cornea, risking rejection in eyes following keratoplasty. Pre-operative (lymph)-angioregression is a promising therapeutic approach, but objective monitoring by non-invasive CV imaging is needed. The purpose of this study was to investigate anterior-segment optical coherence tomography angiography (AS-OCTA) for CV visualization and quantification, and to show its superiority over slit-lamp photography in high-risk eyes scheduled for keratoplasty. This institutional pilot study included 29 eyes of 26 patients (51 ± 16 years, 8 female) with significant CV scheduled for keratoplasty that were imaged by slit-lamp photography (Zeiss SL 800) and AS-OCTA (Zeiss Plex Elite 9000). After manual corneal layer segmentation correction, CV maximum/relative depth was measured with the inbuilt software. Slit-lamp photographs and AS-OCTA images were compared for visualization of vascular details. Angiotool software allowed a semi-automated determination of CV-related parameters in the vascular complex of AS-OCTA images. The predominant causes of CV were the herpes simplex virus keratitis (n = 7) and chemical burn (n = 4). Visualization of vascular morphology in AS-OCTA was superior to slit-lamp photography in all except one eye. Vascular metrics including total vessel length, number of junctions/endpoints, junction density, lacunarity, and vessel area/density were defined using Angiotool, with CV depth localization despite scarring and opacification. AS-OCTA proved effective for angioregressive treatment monitoring. AS-OCTA enables non-invasive and objective three-dimensional visualization of corneal vascularization superior to slit-lamp photography, and could be a precious tool for monitoring angioregressive preconditioning prior to keratoplasty

Graefe's Archive for Clinical and Experimental Ophthalmology / Correlation between central stromal demarcation line depth and changes in K values after corneal cross-linking (CXL)

Purpose A stromal demarcation line (DL) after corneal cross-linking (CXL) has lately been suggested as a surrogate parameter for the success of CXL. The aim of this study was to investigate the correlation between depth of the central DL 1 month and the change in K values 12 months after CXL. Methods Treatment-naive subjects with keratoconus were treated using an accelerated CXL protocol [A-CXL(9*10)]. Depth of the DL/relative depth of the DL (DL%) was measured using Visante OCT imaging 1 month postoperatively (OP). Kmax/K2.5 (preOP) and change in Kmax/K2.5 (preOP12 months postOP) were assessed using corneal tomography (Pentacam HR, Oculus GmBH). Results Forty eyes were treated following the A-CXL(9*10). The mean DL depth was 20099 m (range 71 to 479)/mean DL%=42.7020.00% (range 1790). There was no statistically significant correlation between stromal depth of the DL and change in Kmax or K2.5, respectively (Spearman rho DL/Kmax 0.14 and DL/K2.5 0.14). Between DL% and the changes in maximum K values or K2.5, no statistically significant correlation was found as well (Spearman rho DL%/Kmax 0.10 and DL%/K2.5 0.19). Mean change in Kmax after 12 months was 0.682.26 diopters (D) (median 0.35 D) and 0.821.6 D (median 0.65 D) for K2.5 (p=0.07; p=0.02). Conclusions No statistically significant correlation was found between the stromal central depth of the DL and any outcome parameter for CXL after 12 months. Therefore, the interpretation of the DL as a predictive parameter for the effect of the procedure may not apply.(VLID)357508

Autophagy mediates cell cycle response by regulating nucleocytoplasmic transport of PAX6 in limbal stem cells under ultraviolet-A stress

<div><p>Limbal stem cells (LSC) account for homeostasis and regeneration of corneal epithelium. Solar ultraviolet A (UVA) is the major source causing oxidative damage in the ocular surface. Autophagy, a lysosomal degradation mechanism, is essential for physiologic function and stress defense of stem cells. PAX6, a master transcription factor governing corneal homeostasis by regulating cell cycle and cell fate of LSC, responds to oxidative stress by nucleocytoplasmic shuttling. Impaired autophagy and deregulated PAX6 have been reported in oxidative stress-related ocular surface disorders. We hypothesize a functional role for autophagy and PAX6 in LSC’s stress response to UVA. Therefore, human LSC colonies were irradiated with a sub-lethal dose of UVA and autophagic activity and intracellular reactive oxygen species (ROS) were measured by CYTO-ID assay and CM-H₂DCFDA live staining, respectively. Following UVA irradiation, the percentage of autophagic cells significantly increased in LSC colonies while intracellular ROS levels remained unaffected. siRNA-mediated knockdown (KD) of <i>ATG7</i> abolished UVA-induced autophagy and led to an excessive accumulation of ROS. Upon UVA exposure, LSCs displayed nuclear-to-cytoplasmic translocation of PAX6, while ATG7KD or antioxidant pretreatment largely attenuated the intracellular trafficking event. Immunofluorescence showing downregulation of proliferative marker PCNA and induction of cell cycle regulator p21 indicates cell cycle arrest in UVA-irradiated LSC. Abolishing autophagy, adenoviral-assisted restoration of nuclear PAX6 or antioxidant pretreatment abrogated the UVA-induced cell cycle arrest. Adenoviral expression of an ectopic PAX gene, PAX7, did not affect UVA cell cycle response. Furthermore, knocking down PAX6 attenuated the cell cycle progression of irradiated ATG7KD LSC by de-repressing p21 expression. Collectively, our data suggest a crosstalk between autophagy and PAX6 in regulating cell cycle response of ocular progenitors under UVA stress. Autophagy deficiency leads to impaired intracellular trafficking of PAX6, perturbed redox balance and uncurbed cell cycle progression in UVA-stressed LSCs. The coupling of autophagic machinery and PAX6 in cell cycle regulation represents an attractive therapeutic target for hyperproliferative ocular surface disorders associated with solar radiation.</p></div

Localized opacification of hydrophilic acrylic intraocular lenses after procedures using intracameral injection of air or gas

To describe clinical and laboratory findings in a series of cases of intraocular lens (IOL) opacification after procedures involving intracameral injections of air or gas. John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. Experimental study. Seven hydrophilic acrylic IOLs explanted after Descemet-stripping endothelial keratoplasty (DSEK) or Descemet-stripping automated endothelial keratoplasty (DSAEK) because of a localized central optic opacification associated with decrease in visual acuity and complaints of foggy vision were analyzed. The explanted IOLs were sent to our laboratory in the dry state or in fixative by the explanting surgeons. They underwent pathological and histochemical evaluation (alizarin red and von Kossa method). Light scattering measurements were also performed on the surface of 1 explant using Scheimpflug photography. A questionnaire was sent to the surgeons to obtain information pertinent to each case. The 7 explanted IOLs were represented by 6 hydrophilic acrylic designs from 5 manufacturers. Gross and light microscopy showed that granular deposits were densely distributed in an overall round pattern within the margins of the capsulorhexis or the pupil on the anterior surface/subsurface of the IOLs. The granules stained positive for calcium (alizarin red and von Kossa method). Light scattering on the anterior optic surface was very high (228 versus 13 computer-compatible tapes on a control IOL). A localized pattern of calcification was seen on the anterior surface/subsurface of various hydrophilic acrylic IOLs. Surgeons should be aware of this phenomenon following DSEK/DSAEK procedures in pseudophakic patients with hydrophilic acrylic IOLs. No author has a financial or proprietary interest in any material or method mentione

Autophagy is activated during LSC’s stress response to UVA.

<p>(A) Representative images of autophagosomes in ATG7KD LSCs under UVA stress. Arrowheads show autophagic cells, asterisks indicate absence of autophagosomes. Scale bar, 50 μm. (B) Quantification of cells with autophagic activity in response to UVA. (C) Representative western blot image of autophagic flux in UVA-irradiated LSC colonies in absence and presence of BafA1, with or without UVA. LC3B-I and II were detected by immunoblotting at indicated time points. (D) Densitometric analysis of LC3B-II expression normalized to GAPDH. n = 3, *<i>p</i> < .05.</p

PAX6KD restores UVA-induced, p21-mediated cell cycle arrest in ATG7KD LSC.

<p>(A) Immunofluorescence of p21 in LSC colonies with KD of ATG7, PAX6 or both. Scale bar, 100 μm. (B) Quantification of p21-expressing cells in ATG7KD, PAX6KD or ATG7/PAX6 double KD LSCs. *<i>p</i> < .05, **<i>p</i> < .01.</p