Purpose To investigate the role of corneal epithelium- and Bowman’s layer-thickness (ET and BLT) changes as possible early biomarkers of keratoconus (KC) development. Methods In this cross-sectional study patients with unilateral KC (UKC) and a group of healthy controls underwent polarization sensitive optical coherence tomography (PS-OCT) for the evaluation of corneal ET and BLT. These values were compared among three subgroups of eyes, i.e., eyes with KC, topographically and tomographically normal fellow eyes (FE) of patients with UKC, and healthy eyes (HE). Results Twelve patients with UKC (12 eyes with KC and 12 FE) and 21 healthy age-matched controls (HE) were included. While KC eyes showed the typical epithelial “doughnut pattern” on epithelial maps, there were no differences in ET between FE and HE. BLT was significantly higher in FE compared to HE (average BLT p = 0.049, minimum BLT p = 0.02, nasal-inferior quadrant p = 0.04) as weIl as KC eyes (average BLT p = 0.048, minBLT p = 0.04, nasal-inferior quadrant p = 0.03). Conclusions Increase in BLT seems to occur before epithelial thinning in FE of patients with UKC. Since many of KC patients develop the disease bilaterally, Bowman’s layer thickening might represent an early biomarker of KC-development.

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.

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.

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Using conventional optical coherence tomography (OCT), it is difficult to image Henle fibers (HF) due to their low backscattering potential. However, fibrous structures exhibit form birefringence, which can be exploited to visualize the presence of HF by polarization-sensitive (PS) OCT. We found a slight asymmetry in the retardation pattern of HF in the fovea region that can be associated with the asymmetric decrease of cone density with eccentricity from the fovea. We introduce a new measure based on a PS-OCT assessment of optic axis orientation to estimate the presence of HF at various eccentricities from the fovea in a large cohort of 150 healthy subjects. By comparing a healthy age-matched sub-group (N = 87) to a cohort of 64 early-stage glaucoma patients, we found no significant difference in HF extension but a slightly decreased retardation at about 2° to 7.5° eccentricity from the fovea in the glaucoma patients. This potentially indicates that glaucoma affects this neuronal tissue at an early state.

Optical coherence tomography (OCT) is the most widely used imaging modality in ophthalmology. There are multiple variations of OCT imaging capable of producing complementary information. Thus, registering these complementary volumes is desirable in order to combine their information. In this work, we propose a novel automated pipeline to register OCT images produced by different devices. This pipeline is based on two steps: a multi-modal 2D en-face registration based on deep learning, and a Z-axis (axial axis) registration based on the retinal layer segmentation. We evaluate our method using data from a Heidelberg Spectralis and an experimental PS-OCT device. The empirical results demonstrated high-quality registrations, with mean errors of approximately 46 µm for the 2D registration and 9.59 µm for the Z-axis registration. These registrations may help in multiple clinical applications such as the validation of layer segmentations among others.

Zusammenfassung Hintergrund Durch die rasant steigende Prävalenz der Myopie kommen zunehmend progressionshemmende Verfahren zum Einsatz. Auch die Orthokeratologie, basierend auf dem Ansatz des peripheren Defokus, erlebt eine Renaissance. Die gefährlichste Nebenwirkung der Orthokeratologie ist die mikrobielle Keratitis, unter ihnen eine Infektion mit Akanthamöben, welche oft spät diagnostiziert wird und potenziell visusbedrohende Verläufe nehmen kann. Material und Methode Diese Fallserie beschreibt die Diagnosefindung und den Behandlungsverlauf der Akanthamöbenkeratitis bei jugendlichen Patient*innen mit Orthokeratologielinsen, welche an der Spezialambulanz für Hornhauterkrankungen der Universitätsklinik für Augenheilkunde und Optometrie an der Medizinischen Universität Wien im Zeitraum eines Jahres betreut wurden. Resultate Vier Fälle von orthokeratologieassoziierten Akanthamöbenkeratitiden wurden mittels kornealer Konfokalmikroskopie und mikrobiologischer Verfahren zwischen August 2021 und August 2022 diagnostiziert. Die intensive Stufentherapie umfasste ein hochdosiertes, topisches Biguanid in Kombination mit einem Diamidinderivat, welches in der ersten Therapiephase mit antibakteriellen und antifungalen Augentropfen kombiniert wurde. Der Therapieverlauf und -erfolg wurde mittels der kornealen Konfokalmikroskopie beurteilt, und entsprechend angepasst. Schlussfolgerung Die Akanthamöbenkeratitis ist ein ernst zu nehmendes Erkrankungsbild im Zusammenhang mit Orthokeratologielinsen. Im Hinblick auf das Alter der Zielgruppe dieser myopieprogressionshemmenden Therapie sollte, neben sorgfältiger Patientenselektion, auf eine detaillierte Schulung der Kontaktlinsenträger in der Handhabung der Linsen sowie auf ein erhöhtes Bewusstsein für Zeichen einer frühen Infektion besonderes Augenmerk gelegt werden. Da alternative Möglichkeiten zur Myopieprophylaxe bestehen, müssen PatentInnen auf das Risiko der jeweiligen Methode hingewiesen werden.

BackgroundTo compare graft survival of endothelial keratoplasty (EK) versus penetrating keratoplasty (PK) in patients with iridocorneal endothelial (ICE) syndrome and identify ocular features associated with graft survival. MethodsObservational, prospective, cohort study. A total of 30 806 first grafts performed between 1985 and 2020 were identified through the Australian Corneal Graft Registry and included in this observational, prospective cohort study. A total of 196 eyes underwent a primary corneal graft for ICE syndrome. Kaplan-Meier graft survival plots and Chi-squared tests were performed to identify graft survival rates for EK and PK. A history of raised intraocular pressure (IOP) was also recorded and analysed. Graft survival of eyes with ICE syndrome were compared to that of other indications. ResultsGrafts performed for ICE syndrome increased to 0.8% of all cases during the 2005 to 2020 period compared with 0.5% between 1985 to 2004 (& chi;(2)=9.35, p = 0.002). From 2010, EK surpassed PK as the preferred graft type. Survival of primary grafts in eyes with ICE syndrome was lower than for other indications (log-rank = 56.62, p < 0.001). Graft survival was higher following PK than Descemet stripping (automated) endothelial keratoplasty (DS(A)EK) (log-rank = 10.56, p = 0.001). Graft survival was higher in eyes without a history of raised IOP compared to those with a reported history of raised IOP (log-rank = 13.06, p < 0.001). ConclusionsICE syndrome carries a poor prognosis for graft survival. DS(A)EK had a poorer prognosis than PK. A history of raised IOP is associated with higher risk of graft failure.

Background: With the rapidly increasing prevalence of myopia, progression-inhibiting techniques such as orthokeratology are increasingly being used; however, they harbor the risk of microbial keratitis, including Acanthamoeba infection, which is associated with delayed diagnosis, prolonged treatment and a potentially vision-threatening outcome.Material and method: This case series describes the diagnosis and course of treatment in four cases of Acanthamoeba keratitis in adolescents associated with the use of orthokeratology lenses, who were treated at the outpatient clinic for corneal diseases of the Department of Ophthalmology and Optometry at the Medical University of Vienna over a period of 1 year.Results: The four cases of orthokeratology-associated Acanthamoeba keratitis were diagnosed using corneal confocal microscopy and microbiological methods between August 2021 and August 2022. The intensive stepwise therapeutic approach included a high-dose, topical biguanide in combination with a diamidine derivative, which was combined with antibacterial and antifungal eye drops in the first phase of treatment. The course and success of the treatment was assessed using corneal confocal microscopy and adapted accordingly.Conclusion: Acanthamoeba keratitis is a serious infection associated with orthokeratology lenses. With respect to the age of the target group of this myopia progression-inhibiting treatment, besides careful patient selection, special attention should be paid to detailed training of contact lens wearers in the handling of the lenses as well as to an increased awareness of signs of early infection. As other methods for myopia control are available, patients need to be informed about the infection risk of orthokeratology.

We present measurements of depolarization introduced by the retinal pigment epithelium (RPE) over a 45° field of view using polarization sensitive optical coherence tomography. A detailed spatial distribution analysis of depolarization caused by the RPE is presented in a total of 153 subjects including both healthy and diseased eyes. Age and sex related differences in the depolarizing character of the RPE are investigated.

Dear Editor,We present a case of a healthy 32-year-old man who developed bilateral corneal ulceration 3 wk after commencing dupilumab for atopic dermatitis. Dupilumab is a recently introduced systemic monoclonal antibody used in the treatment of moderate-to-severe atopic dermatitis, showing efficacy in clinical trials [1-4] . Several publications have reported ocular surface complications associated with dupilumab,

center dot PURPOSE: The purpose of this study was to investigate epithelial and neuronal changes in patients with refrac-tory/relapsed multiple myeloma (RRMM) before/during belantamab mafodotin (belamaf) treatment using confo-cal microscopy.center dot DESIGN: Retrospective case series.center dot METHODS: RRMM patients underwent best-corrected visual acuity (BCVA) testing and slitlamp examina-tion/photography, followed by corneal confocal mi-croscopy (CCM), to evaluate the epithelium and subbasal nerve plexus (SNP) to measure corneal nerve fiber den-sity (CNFD), branch density (CNBD), and fiber length (CNFL) before and during belamaf treatment.center dot 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 biomi-croscopically. CCM showed "grape-like" hyperreflective spots in the central basal epithelium that changed to polymorphous-structured cysts in the superficial epithe-lium, 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 respec-tively, showed severe fiber fragmentation during follow-up, and an observed complete loss of the SNP at the end of follow-up in all eyes.center dot CONCLUSIONS: This study is the first to illus-trate neurotoxic effects of belamaf on the human cornea. (Am J Ophthalmol 2022;242: 116-124. (c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC -ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ))

The depolarization capabilities of the retinal pigment epithelium (RPE) are known to be dependent on the position at the macula and may be caused or influenced by the concentration of melanin and lipofuscin. In this work, the depolarization distribution of the RPE in a large group of healthy eyes is investigated using polarization-sensitive OCT by calculating the degree of polarization uniformity (DOPU) in a large field of view. The results are compared to diseased eyes (glaucoma, age-related macular degeneration), which might help to detect early pathologic changes of the RPE.

To find baseline predictors for subretinal fibrosis (SF) in neovascular age-related macular degeneration (nAMD). Forty-five eyes of 45 participants with treatment-naïve nAMD were consecutively enrolled and treated according to a standardized treat-and-extend protocol. Spectral-domain optical coherence tomography (OCT), color fundus photography and fluorescein angiography as well as novel imaging modalities polarization-sensitive OCT and OCT angiography (OCTA) were performed to detect SF after 1 year and find baseline predictors for SF development. Baseline OCTA scans were evaluated for quantitative features such as lesion area, vessel area, vessel junctions, vessel length, vessel endpoints and mean lacunarity. Additionally, the type of macular neovascularization, the presence of subretinal fluid, intraretinal fluid (IRF), subretinal hyperreflective material (SHRM), retinal hemorrhage as well as best-corrected visual acuity (BCVA) were evaluated. After 12 months 8 eyes (18%) developed SF. Eyes with SF had worse baseline BCVA (p = .001) and a higher prevalence of IRF (p = .014) and SHRM at baseline (p = .017). There was no significant difference in any of the evaluated quantitative OCTA parameters (p > .05) between eyes with and without SF. There were no quantitative baseline microvascular predictors for SF in our study. Low baseline BCVA, the presence of IRF and SHRM, however, are easily identifiable baseline parameters indicating increased risk.

PURPOSE:To identify correlations between the vascular characteristics of macular neovascularization (MNV) obtained by optical coherence tomography angiography (OCTA) and distinct retinal fluid volumes in neovascular age-related macular degeneration (nAMD). METHODS:In this prospective interventional study, 54 patients with treatment-naïve type 1 or 2 nAMD were included and treated with intravitreal aflibercept. At baseline and month 1, each patient underwent a SD-OCT volume scan and volumetric flow scan using a swept-source OCTA. A deep learning algorithm was used to automatically detect and quantify fluid in OCT scans. Angio Tool, a National Cancer Institute algorithm, was used to skeletonize MNV properties and quantify lesion size (LS), vessel area (VA), vessel density (VD), total number of endpoints (TNE), total number of junctions (TNJ), junction density (JD), total vessel length (TVL), average vessel length (AVL) and mean-e-lacunarity (MEL). Subsequently, linear regression models were used to investigate a correlation between OCTA parameters and fluid quantifications. RESULTS:The median amount of fluid within the central 6-mm EDTRS ring was 173.7 nl at baseline, consisting of 156.6 nl of subretinal fluid (SRF) and 2.3 nl of intraretinal fluid (IRF). Fluid decreased significantly in all compartments to 1.76 nl (SRF) and 0.64 nl (IRF). The investigated MNV parameters did not change significantly after the first treatment. There was no significant correlation between MNV parameters and relative fluid decrease after anti-VEGF treatment. Baseline fluid correlated statistically significant but weakly with TNE (p = 0.002, R2  = 0.17), SRF with TVL (p = 0.04, R2  = 0.08), VD (p = 0.046, R2  = 0.08), TNE (p = 0.001, R2  = 0.20) and LS (p = 0.033, R2  = 0.09). IRF correlated with VA (p = 0.042, R2  = 0.08).The amount of IRF at month 1 correlated significantly but weakly with VD (p = 0.036, R2  = 0.08), JD (p = 0.019, R2  = 0.10) and MEL (p = 0.005, R2  = 0.14). CONCLUSION:Macular neovascularization parameters at baseline and month 1 played only a minor role in the exudation process in nAMD. None of the MNV parameters were correlated with the treatment response.

This work introduces a method to objectively and non-invasively detect subretinal fibrosis secondary to neovascular age-related macular degeneration. The method exploits the birefringent properties of fibrous tissue: the axis orientation of fibrous tissues is well-defined, whereas the axis orientation of non-fibrous tissues is random. After removal of the influences from birefringent tissues anterior to the fibrosis, fibrotic scar tissues were the only remaining areas with uniform axis orientation and therefore became distinguishable from healthy tissue. The algorithm detected fibrosis congruent to color fundus photography, which is the current gold standard to diagnose fibrosis.

Subretinal fibrosis is one of the most prevalent causes of blindness in the elderly population, but a true gold standard to objectively diagnose fibrosis is still lacking. Since fibrotic tissue is birefringent, it can be detected by polarization-sensitive optical coherence tomography (PS-OCT). We present a new algorithm to automatically detect, segment, and quantify fibrotic lesions within 3D data sets recorded by PS-OCT. The algorithm first compensates for the birefringence of anterior ocular tissues and then uses the uniformity of the birefringent optic axis as an indicator to identify fibrotic tissue, which is then segmented and quantified. The algorithm was applied to 3D volumes recorded in 57 eyes of 57 patients with neovascular age-related macular degeneration using a spectral domain PS-OCT system. The results of fibrosis detection were compared to the clinical diagnosis based on color fundus photography (CFP), and the precision of fibrotic area measurement was assessed by three repeated measurements in a sub-set of 15 eyes. The average standard deviation of the fibrotic area obtained in eyes with a lesion area > 0.7 mm 2 was 15%. Fibrosis detection by CFP and PS-OCT agreed in 48 cases, discrepancies were only observed in cases of lesion area < 0.7 mm 2 . These remaining discrepancies are discussed, and a new method to treat ambiguous cases is presented.