The role of graft cross-linking during keratoplasty in patients with corneal melting.

The purpose of this study was to investigate the role of corneal crosslinking (CXL) of grafts during keratoplasty (KP) in patients with refractory corneal melting (CM). This is a retrospective case series reporting the clinical outcomes of patients who received a crosslinked corneal graft during penetrating or deep anterior lamellar KP for refractory infectious or sterile CMs. Outcome measures were the recurrence of CM, the time required for epithelial healing following KP, incidence of complications, and necessity for re-transplantation. Twenty eyes of 18 patients with a follow-up of 29.2 ± 15.8 months were included in this study. All but two eyes had undergone previous KPs during the course of their disease (mean 1.9 ± 1.6). After CXL-enhanced KP, three eyes (15%) experienced recurrence of CM, three eyes developed an infectious keratitis and six eyes (30%) required a re-transplantation (three of them within 12 months). The mean time to epithelium closure after CXL-enhanced KP was 63 ± 90 days. The number of postoperative re-transplantations was significantly lower than the number of KPs performed before the CXL-enhanced transplantation (before CXL 1.9 ± 1.6 vs after CXL: 0.3 ± 0.57, p = 0.002). To conclude, CXL of the graft at the time of keratoplasty decreased the need for re-transplantations. However, further studies are needed in order to establish its role in the management of severe CM necessitating therapeutic corneal transplantation.

Clinical outcome analysis of two approaches to trypan blue dyeing for DMEK.

To evaluate the clinical implications of the different trypan blue dyeing techniques used during liquid bubble (LBT) and manual peel (MPT) DMEK lenticule preparation techniques. This study retrospectively compared the degree to which endothelial cells are preserved using selective Descemet Membrane (DM) staining (LBT) versus bath-staining (MPT) when performed by a single surgeon, sourced from a single eye bank. Endothelial cell density measured after the 3-month follow-up was 1805 and 1916 cells/mm2 respectively, differing significantly (p = 0.012). A double-scroll graft formation was found and maintained until implantation in 94% of preparations with bath staining and 50% of preparations using selective DM staining. Preoperative visual acuity was comparable between preparation techniques at 0.4 logMAR as well as postoperatively, at an average of 0.1 logMAR. Reducing chemical stress on the endothelium by avoiding any contact with trypan blue allows for a significantly higher degree of cell preservation. However, achieving the often-desired double-scroll graft formation was possible less frequently. It remains unclear which factors define the differences graft scrolling behavior observed between LBT and MPT.

Monitoring the Effectiveness of High-Fluence Peripheral Crosslinking for Corneal Neovascularization with Anterior Segment Optical Coherence Tomography Angiography.

Background/Aims: To investigate the effectiveness of an accelerated high-fluence peripheral crosslinking (pCXL) treatment protocol for corneal neovascularization (cNV) and the viability of optical coherence tomography angiography (OCTA) to monitor cNV dynamics. Methods: This pilot study included six eyes of six adult patients with cNV in at least one corneal quadrant who were treated with pCXL (7.2 J/cm2, 9 mW). The degree of cNV regression was monitored with slit lamp photography and anterior segment OCTA. The main outcome measure was total vessel area one and four weeks after treatment. Results: OCTA allowed for the objective monitoring of vascular metrics: The total vessel area declined from an average of 1025.4 mm2 (min: 0.13 mm2; max: 3637 mm2) at the baseline evaluation to 382.4 mm2 (min: 0.08 mm2; max: 1528 mm2) (p = 0.096). The total vessel length lessened from an average of 107.1 mm (min: 2.8 mm; max: 321.1 mm) to 47 mm (min: 2.6 mm; max: 156.5 mm) (p= 0.27). The average number of junctions at baseline decreased from 46.67 (min: 3; max: 166) to 26.5 (min: 0; max: 50) (p = 0.23). The junction density decreased from an average of 10.75/mm2 (min: 0.0002 /mm2; max: 36.5056/mm2) to 7.37/mm2 (avg.) (min: 0; max 18.7356/mm2) (p = 0.24). PCXL was performed safely without adverse effects, but vascular occlusion was not complete in all eyes. Conclusions: High-fluence pCXL may represent a valuable treatment option to achieve cNV regression, whilst the optimal fluence dose still remains to be defined. Anterior segment OCTA is an innovative tool for non-invasive, objective, and quantitative cNV monitoring.

Anterior Chamber Air Bubble Dynamics With Decreases in Atmospheric Pressure.

PURPOSE: To evaluate the effect of decreasing barometric pressure on intracameral bubble size and intraocular pressure (IOP) in eyes with varying air fills in the anterior chamber. METHODS: A total of 36 human donor eyes received 30%, 50%, or 90% anterior chamber air fill. The eyes were subjected to decreases in atmospheric pressure down to 750 hPa, equal to 2400 m in altitude, and were repeatedly imaged using anterior segment OCT while IOP was measured continuously. RESULTS: Eyes with 30% air fill initially showed moderate increases in IOP yet rising to an average of 30.83 mm Hg at 850 hPa (mimicking 1400 m altitude) and 42.08 mm Hg at 750 hPa. Eyes with larger air bubbles showed more acute increases in IOP with increases to an average of 47.25 mm Hg in eyes with 50% air fill at 850 hPa and 63.33 mm Hg at 750 hPa. In eyes with 90% air fill in the anterior chamber, IOP readings with an average of 113.42 mm Hg were observed already at 850 hPa, at which point additional pressure reduction was not performed. CONCLUSIONS: While severe increases in IOP were observed with decreased atmospheric pressure in eyes with large air bubbles in the anterior chamber, small and moderately sized bubbles seem to allow for travel over modest changes in altitude.

Nonpenetrating Foldable Intrastromal Keratoprosthesis: A Review of the Literature.

PURPOSE: To review the literature focusing on the clinical outcomes of KeraKlear (KK) (KeraMed), a foldable intrastromal keratoprosthesis. METHODS: We searched 6 databases using 4 keywords: KeraKlear, Foldable Keratoprosthesis, Intrastromal Keratoprosthesis, and Non-penetrating Keratoprosthesis. Included studies had to be conducted in vivo on humans, published until January 3, 2023, and had to investigate the implantation of the KK. Eyes were considered at high risk of keratoprosthesis retention failure whenever there was an active inflammatory ocular surface disorder or in case of previous KK failure. We aimed at recording the postoperative complications, rate of prosthesis retention, and mean improvements in visual acuity. RESULTS: We identified 144 publications, 6 of which (38 eyes) met the inclusion criteria. No randomized controlled trials were found, and some studies had significant limitations regarding sample size and follow-up duration. With a mean follow-up of 28 ± 18.8 months, postoperative complications of any kind occurred between 0% and 50% and 24% had an implant extrusion/needed a reoperation. The mean postoperative visual acuity improvement on the last follow-up was -0.83 ± 0.27 LogMAR, that is, -0.57 ± 0.3 for high-risk and -1.03 ± 0.25 for low-risk eyes, whereas 1 year after implantation, 50% of the prostheses were retained in the former and 81% in the latter group. None of the eyes developed glaucoma, endophthalmitis, or expulsive hemorrhages; none had to be eviscerated/enucleated. CONCLUSIONS: Despite the limited quality and quantity of evidence, the available literature seems to suggest the KK to be a valuable tool in the treatment of complicated corneal disorders. Because in many parts of the world, the access to corneal transplantation is limited, this prosthesis could represent a valid alternative.

Predictive factors for re-bubbling after DMEK: focus on the posterior corneal surface.

PURPOSE: To understand whether the preoperative morphology of the posterior corneal surface influences the rate of re-bubbling after Descemet membrane endothelial keratoplasty (DMEK). METHODS: After retrospectively analyzing the medical records of patients undergoing DMEK, in this multicentric cross-sectional study, we performed a binomial logistic regression analysis to assess significant predictors of re-bubbling and re-transplantation after surgery. Analyzed parameters included the preoperative diagnosis, anterior and posterior surface K1/K2, central corneal thickness, posterior Q value, and other posterior corneal surface parameters evaluated on the elevation maps produced by anterior segment optical coherence tomography. Results were stratified based on the surgeons' experience. RESULTS: We included 202 eyes of 202 patients with a mean age of 69.5 ± 12.4 years; 154 eyes were operated by a high-volume surgeon and 48 by one with less experience; 48 eyes (23.8%) underwent ≥ 1 re-bubbling and 14(6.9%) ≥ 1 re-transplantation. The presence of positive/less-negative posterior corneal irregularities and irregularities with greater absolute height had a significantly higher risk of re-bubbling in both the expert and less expert group (OR = 2.85 and 1.42, OR = 3.22 and 3.01, respectively, p < 0.05), whereas more negative posterior K1 and K2 were significant risk factors only in the former group (OR = 0.67 and 0.55, respectively, p < 0.05). Endothelial decompensation other than Fuchs and pseudophakic bullous keratopathy, more negative posterior Q values and smaller distances between center, and the highest/lowest posterior corneal surface irregularity correlated with an increased risk of graft failure (OR 1.23, 1.21, and 1.29, respectively, p < 0.05). CONCLUSION: Posterior corneal surface morphology significantly influences the risk of re-bubbling after DMEK.

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

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.

Identification of Treatment Protocols for Effective Cross-Linking of the Peripheral Cornea: An Experimental Study.

INTRODUCTION: This study aimed to test and evaluate modified corneal cross-linking (CXL) protocols regarding improved treatment effects on the peripheral cornea in terms of tissue stability and cellular response. METHODS: Peripheral CXL (pCXL) was performed within a ring of 9-11 mm of 36 human donor corneas with variations in applied energy (5.4, 7.2, and 10 J/cm2) at 9 mW/cm2 irradiance. Each energy level was additionally modulated regarding the oxygen level surrounding the cornea during treatment (21%; 100%). Stress-strain tests with endpoints at 12% strain and collagenase A-assisted digestions to complete digestion were performed to evaluate the rigidity and resistance of treated and control tissue. Further, corneas were processed histologically via TUNEL assay and H&E staining to demonstrate the effects on stromal cells during treatment under varying CXL conditions. RESULTS: Increases in energy dosage achieved significant increases in resistance to stress in all variations except when comparing protocols A and B under normoxic conditions. Supplemental oxygen significantly increased rigidity in protocols B (p < 0.01) and C (p = 0.018). Hyperoxic conditions significantly increased resistance to digestion in all protocols. The number of DNA strand breaks in TUNEL assay staining showed significant increases in all increases in energy as well as with oxygen supplementation. CONCLUSIONS: Increases in energy and supplemental oxygen improved the effect of CXL, though endothelial safety could not be verified with confidence in high-fluence CXL with supplemental oxygen. Results suggest that CXL protocols using 7.2 J/cm2 with 100% O2 or 10 J/cm2 without supplemental oxygen prove most effective without anticipated risk of endothelial damage.

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.

Corneal Toxicity Associated With Belantamab Mafodotin Is Not Restricted to the Epithelium: Neuropathy Studied With Confocal Microscopy.

PURPOSE: The purpose of this study was to investigate epithelial and neuronal changes in patients with refractory/relapsed multiple myeloma (RRMM) before/during belantamab mafodotin (belamaf) treatment using confocal microscopy. DESIGN: Retrospective case series. METHODS: RRMM patients underwent best-corrected visual acuity (BCVA) testing and slitlamp examination/photography, followed by corneal confocal microscopy (CCM), to evaluate the epithelium and subbasal nerve plexus (SNP) to measure corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) before and during belamaf treatment. RESULTS: In 14 eyes of 7 patients (4 female, 68 ± 10 years of age) with complete follow-up (4 ± 2 months), the median BCVA dropped from 20/25 (20/25-20/20) to 20/40 (20/200-20/32) in the worse eye at the end of follow-up. Microcystic epithelial changes and ocular surface disease were demonstrated biomicroscopically. CCM showed "grape-like" hyperreflective spots in the central basal epithelium that changed to polymorphous-structured cysts in the superficial epithelium, with no pathology detected at the(peri-)limbal structures. The baseline, normal SNP morphology with a mean CNFD, CNBD, and CNFL of 20.25 ± 7.06/mm2, 19.49 ± 12.34/mm2, and 11.8 ± 3.74mm/mm2 respectively, showed severe fiber fragmentation during follow-up, and an observed complete loss of the SNP at the end of follow-up in all eyes. CONCLUSIONS: This study is the first to illustrate neurotoxic effects of belamaf on the human cornea.

Decompensated cornea with epithelial and stromal edema.

A 66-year-old patient underwent surgery for congenital cataract in both eyes in her first year of life without implantation of an intraocular lens (IOL). In 1994, at the age of 39 years, both eyes received secondary Kelman multiflex-style angle-fixated anterior chamber IOLs (AC IOLs). The surgeries were followed by retinal detachments in both eyes, in the left eye in the same year and in the right eye 4 years later, which were successfully repaired. The patient presented with a decompensated cornea with epithelial and stromal edema in the left eye. The AC IOL axis was oriented from 5- to 8-o'clock position with the haptic contacting the cornea. The distal portion of the inferior-nasal haptic was deeply buried and entrapped in a broad iridocorneal synechia extending between 6- and 8-o'clock positions. The synechia also caused adjacent pupillary distortion and pigment leaf eversion (Figure 1JOURNAL/jcrs/04.03/02158034-202205000-00021/figure1/v/2022-04-22T173532Z/r/image-tiff). The AC IOL in the right eye was well positioned, and the cornea was clear with an endothelial cell count (ECC) of 2160 cells/mm2 and central corneal thickness (CCT) of 650 µm. No ECC was obtainable in the left eye, and CCT was 775 µm (Figure 2JOURNAL/jcrs/04.03/02158034-202205000-00021/figure2/v/2022-04-22T173532Z/r/image-tiff). Visual acuity was 0.8 corrected in the right eye and hand motion in the left eye. Both eyes were normotonic. On optical coherence tomography (OCT) imaging, a broad iridocorneal synechia was visible with a canal corresponding to the deeply buried haptic end of the AC IOL (Figure 3JOURNAL/jcrs/04.03/02158034-202205000-00021/figure3/v/2022-04-22T173532Z/r/image-tiff). Abundant condensed cortical material (Soemmerring's ring) was found behind the iris and above the ciliary body. What would be your surgical options to rehabilitate the patient's left eye considering corneal decompensation caused by haptic contact of an angle-fixated AC IOL and capture of 1 haptic within an iridocorneal synechia extending along 2 clock hours?

Atezolizumab induced immune-related adverse event mimicking conjunctival metastatic disease.

Purpose: To describe a case of an immune-related adverse event associated with Atezolizumab therapy which was aggravated by ocular surgery. Observations: A 59-year-old man treated with Atezolizumab for metastatic non-small-cell lung cancer developed a conjunctival hypertrophic lesion mistaken for metastatic tissue. Biopsy surgery induced fulminant and multifocal granulomatous conjunctival tissue growth and sterile corneal ulceration. The immune-related adverse event was refractory to topical therapy, with curative success only after introduction of systemic prednisone. Conclusions: Atezolizumab use may be associated with severe and recalcitrant ocular surface inflammation with potential exacerbation after surgical interventions.

Effects of femtosecond laser-assisted trephination on donor tissue in liquid interface as compared to applanated interface.

PURPOSE: To evaluate the effects of femtosecond laser-assisted keratoplasty using a liquid patient interface (L-PI) as opposed to an applanated interface (A-PI) on graft quality and functionality markers. METHODS: Pressure measurements during femtosecond laser-assisted trephination were performed using two groups of 10 porcine eyes. Trephination was performed either in an L-PI or in an A-PI setting. Pressure sensor needles placed intravitreally continuously recorded intraocular pressure during trephination. Twenty paired human donor eyes were used to test the morphological quality of donor tissue after trephination in L-PI and A-PI settings. Optical coherence tomography (OCT) scans were performed before and after trephination. Images were processed using ImageJ and pixel2 . RESULTS: During trephination, pressure measurements with an L-PI were significantly lower than with an A-PI (p = 0.0121). Mean pressure during trephination was 78.1 mmHg ± 37.6 mmHg with L-PI and 188.6 mmHg ± 17.7 mmHg with A-PI. Trephination in A-PI produced a significantly larger increase (p < 0.00001) in donor pachymetry than trephination in L-PI. Significantly lower areas of Descemet folds were achieved in L-PI trephination than in A-PI trephination (p < 0.01). There was no significant difference in circularity between A-PI and L-PI (p = 0.27). Total time required for trephination was comparable between L-PI and A-PI (p = 0.45). Time taken to reach working vacuum was achieved significantly more quickly in L-PI (p < 0.05). CONCLUSION: Femtosecond laser-assisted L-PI keratoplasty appears to be a promising method to decrease stress to donor and recipient tissue during femtosecond laser-assisted trephination. Results showed favourable donor tissue morphology markers after L-PI trephination.

Endothelial Safety and Efficacy of Ex Vivo Collagen Cross-linking of Human Corneal Transplants.

PURPOSE: To assess endothelial safety and efficacy of ex vivo corneal collagen cross-linking (CXL) in human corneal transplants stored in 2 different culture media. DESIGN: Fellow-eye controlled laboratory study of ex vivo human donor corneas. METHODS: Three sets of paired human donor corneas, 5 pairs each, were stored in organ culture medium before deswelling either at 31 C or at room temperature. One eye of each pair was cross-linked by 0.1% riboflavin in hydroxylpropyl methylcellulose (HPMC) instillation for 10 minutes followed by 10 minutes of ultraviolet-A (9 mW/cm2) irradiation while contralateral eyes served as controls. In Set 1, endothelial cell densities were determined. In Set 2, paired samples were assigned to the 2 deswelling media and CXL efficacy was assessed comparing to untreated controls using collagenase-A-assisted enzymatic digestion. In Set 3, biomechanical testing was performed in the eye pairs (treated vs control) by stress/strain measurements. RESULTS: There was no difference in endothelial cell counts between CXL samples and controls (P = .21). No statistically significant difference in digestion dynamics was found between tissues stored in the 2 different culture media. Complete enzymatic digestion was slowed down by 3 hours in the cross-linked samples (P = .036). Stress needed for a 12% strain was increased by 34% in the treatment group compared to control (P = .04). CONCLUSIONS: Ex vivo CXL of human donor tissue is an effective and safe procedure with no difference regarding efficacy between 2 commercially available deswelling media. Biochemical and biomechanical resistance were significantly increased after CXL. Patients requiring keratoplasty owing to corneal melting might benefit from the strengthening effect of preoperative CXL of donor tissue.

Large Field of View Corneal Epithelium and Bowman's Layer Thickness Maps in Keratoconic and Healthy Eyes.

PURPOSE: To assess differences between epithelium thickness (ET) and Bowman's layer thickness (BLT) maps in keratoconic eyes and healthy eyes. DESIGN: Cross-sectional study. METHODS: Setting: institutional. STUDY POPULATION: 47 patients (1 eye) with keratoconus (KC) and 20 healthy subjects (1 eye). OBSERVATION PROCEDURE: epithelium and Bowman's layer measurements were performed by using custom-designed polarization-sensitive optical coherence tomography (PS-OCT) with a conical scanning optics design. En face corneal ET and BLT maps with a diameter of 11 mm were computed. Main outcome measurements were mean ET and BLT of 25 sectors; the thinnest (minET, minBLT) and thickest sectors (maxET, maxBLT) were assessed. Ratios between thinnest/thickest sectors (R1) and between mean ET and BLT of the inferior temporal quadrant/superior nasal quadrant (R2) were calculated (R1ET, R1BLT; R2ET, R2BLT). Receiver operator characteristic (ROC) curve analysis was used to assess the diagnostic power of statistically different parameters. RESULTS: In healthy eyes, smooth ET maps were observed. KC eyes showed a "doughnut pattern." The BLT maps of healthy eyes had a smooth appearance, but highly irregular "moth"-like damage pattern could be observed in keratoconic eyes. Highest area under the curve values were found for the thinnest sector of the BLT map, the R1ET, and the thinnest sector of the ET map. CONCLUSIONS: PS-OCT imaging enables the visualization of significant differences of the corneal epithelium and the Bowman's layer in en face maps covering almost the entire cornea. ET and BLT profiles could clearly show their diagnostic importance for the distinguishing of keratoconic eyes and healthy eyes.

Corneal crosslinking for pellucid marginal degeneration.

PURPOSE: To investigate the efficacy of corneal crosslinking (CXL) for pellucid marginal degeneration (PMD). SETTING: Medical University of Vienna. DESIGN: Retrospective study. METHODS: In eyes with a crab-claw pattern on corneal topography of a study cohort of 808 eyes, manual measurements of the cornea's thinnest point on the inferior vertical Scheimpflug image (mCTi) and on the superior vertical Scheimpflug image (mCTs) were conducted. Eyes with paralimbal thinning were supposed as having PMD and included. A ratio between mCTi and mCTs was calculated. CXL was performed by irradiation of the inferior periphery of the cornea. During the follow-up, the mCTi, the mean keratometry (K) values in a central zone of 5.0 mm and in a 2.5 mm zone of the inferior cornea and the topographical corneal astigmatism were measured. The corrected distance visual acuity (CDVA) was also evaluated. Patients were followed postoperatively for 12 months. RESULTS: Forty-eight eyes showed a crab-claw pattern in corneal topography. Twenty-two eyes matched the inclusion criteria for PMD and 16 eyes underwent CXL. The mCTi increased during the 12-month follow-up. The K value in the 2.5 mm zone of the inferior cornea decreased after 1 year, whereas the K value in the central zone of 5.0 mm remained stable. The corneal astigmatism continuously decreased, and the CDVA improved after 1 year. CONCLUSION: Manual pachymetric measurements in Scheimpflug images showed the potential for screening for PMD and the evaluation of the efficacy of CXL in eyes with PMD in the study cohort. A thickening of the mCTi and a flattening in the inferior part of the cornea was observed.

CorneaNet: fast segmentation of cornea OCT scans of healthy and keratoconic eyes using deep learning.

Deep learning has dramatically improved object recognition, speech recognition, medical image analysis and many other fields. Optical coherence tomography (OCT) has become a standard of care imaging modality for ophthalmology. We asked whether deep learning could be used to segment cornea OCT images. Using a custom-built ultrahigh-resolution OCT system, we scanned 72 healthy eyes and 70 keratoconic eyes. In total, 20,160 images were labeled and used for the training in a supervised learning approach. A custom neural network architecture called CorneaNet was designed and trained. Our results show that CorneaNet is able to segment both healthy and keratoconus images with high accuracy (validation accuracy: 99.56%). Thickness maps of the three main corneal layers (epithelium, Bowman's layer and stroma) were generated both in healthy subjects and subjects suffering from keratoconus. CorneaNet is more than 50 times faster than our previous algorithm. Our results show that deep learning algorithms can be used for OCT image segmentation and could be applied in various clinical settings. In particular, CorneaNet could be used for early detection of keratoconus and more generally to study other diseases altering corneal morphology.

Ultrahigh-resolution anterior segment optical coherence tomography for analysis of corneal microarchitecture during wound healing.

PURPOSE: To employ ultrahigh-resolution (UHR) optical coherence tomography (OCT) for investigation of the early wound healing process in corneal epithelium. METHODS: A custom-built UHR-OCT system assessed epithelial healing in human keratoconic cornea after epi-off crosslinking (CXL) procedure and a wound healing model in rabbits with iatrogenic corneal injury. 3D OCT data sets enhanced obtaining epithelial thickness maps and evaluation of reepithelization stage. Accompanying changes in deeper corneal microarchitecture were analysed. RESULTS: The mean central corneal thickness in 40 eyes with keratoconus at baseline was 482.7 ± 38.2 µm, while mean central epithelial thickness (CET) was 43.8 ± 6.4 µm. At the final visit 20 ± 5 days post-CXL procedure, CET was 35.0 ± 5.8 µm, significantly thinner after reepithelization (p < 0.001). Surgical success was assessed at the final visit through the demarcation line (DL), identified at 43.7 ± 13.5% stromal depth. In rabbits, the mean CET in 20 eyes at baseline was 35.9 ± 2.6 µm. In rabbits that revealed complete wound closure (10/20 eyes) at the last study day at 72 hr, CET was significantly thinner compared to baseline (30.4 ± 2.8 µm versus 35.4 ± 2.9 µm, p = 0.005). An intra-stromal landmark indicating early keratocyte apoptosis was measured at 30.0 ± 5.1% stromal depth. Epithelial thickness maps showed the time-course of corneal healing. CONCLUSION: Ultrahigh-resolution (UHR)-OCT provided precise assessment of epithelial wound and its healing by 3D-mapping. In addition, microarchitectural changes in the cornea in early phases of epithelial healing were revealed.

Mapping of Corneal Layer Thicknesses With Polarization-Sensitive Optical Coherence Tomography Using a Conical Scan Pattern.

Purpose: We demonstrate segmentation and mapping of corneal layers (epithelium, Bowman's layer, and stroma) across the entire cornea (limbus to limbus), using additional contrast provided by polarization-sensitive optical coherence tomography (PS-OCT) and analyze the reproducibility of the procedure. Methods: A custom built PS-OCT system operating at 1045 nm central wavelength with conical scanning was used for image acquisition. Conical scanning allows for almost perpendicular beam incidence on the corneal surface and provides good signal quality over the entire field of view. Epithelium, Bowman's layer, and stroma were segmented using the additional contrast provided by PS-OCT. Thickness maps were computed and analyzed in sectors. Both eyes of 20 healthy volunteers were imaged at least three times to test this method and to quantify reproducibility. Results: Thickness maps of the epithelium show significant (P < 0.001) superior thinning and an inferior thickening. Bowman's layer appears homogeneous within the central 7 to 8 mm diameter of the cornea and gets thinner toward the periphery until this layer disappears between 4 and 5.5 mm eccentricity from the center. Intersubject variations of the measured thicknesses of epithelium (coefficient of variation [CV] ∼8%), Bowman's layer (CV∼25%), and stroma (CV∼10%) were observed. Very good reproducibility of thickness measurements of epithelium (CV < 3%), Bowman's layer (CV < 5%), and stroma (CV < 2%) was found. Furthermore, a significant correlation (P < 0.001) between layer thicknesses of the right and left eyes of the same subject was found. Conclusions: PS-OCT with conical scanning is a feasible approach for determining thickness maps of corneal layers on a large field of view with high reproducibility.

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 (preOP - 12 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 200 ± 99 µm (range 71 to 479)/mean DL% = 42.70 ± 20.00% (range 17-90). 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 - 0.68 ± 2.26 diopters (D) (median - 0.35 D) and - 0.82 ± 1.6 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.