The Use of Corneoscleral Grafts to Maintain Tectonic Stability in Severe Keratolysis.

Severe corneal ulcerations, causing major keratolysis with large perforation of the cornea or extending to the limbal region, are an ophthalmic emergency. In these cases, a larger corneoscleral graft can be transplanted to restore tectonic integrity, alleviate pain, save vision, and prevent loss of the eye. Chart review of 34 patients with a corneoscleral graft ≥9.5 mm was conducted. Primary endpoints of the study were tectonic stability defined as no need for another keratoplasty or enucleation. In addition, visual acuity, postoperative complications, and secondary procedures were analyzed. In total, 12 patients (35%) were female. The mean age at transplantation was 65 ± 19 years. The underlying disease was a perforated infectious corneal ulcer in 30 cases (88%). Mean follow up was 675 ± 789 days. Tectonic stability at the end of the follow-up was maintained with a probability of 56% in a Kaplan-Meier analysis. Another penetrating keratoplasty was necessary in six cases (17%) and enucleation in five cases (15%). A corneoscleral transplant remains a viable treatment option to prevent enucleation in severe keratolysis. In our study, this was possible in about half of the cases. Postoperative complications, secondary surgeries, and markedly reduced visual acuity put the advantages into perspective.

Successful treatment of multidrug-resistant Pseudomonas aeruginosa keratitis with meropenem eye drops - a case report.

BACKGROUND: This case report describes the course and therapeutic management of a fast-spreading bacterial keratitis caused by multidrug-resistant (MDR) Pseudomonas aeruginosa (P. aeruginosa). CASE PRESENTATION: A 27-year-old male contact lens wearer presented with a multi-resistant, fast spreading P. aeruginosa keratitis. After initial resistance to various antibiotic therapies, testing revealed a MDR P. aeruginosa. The keratitis was treated successfully with specially prepared 50 mg/ml off-label meropenem eye drops for 18 days as well as systemic meropenem for seven days with rapid improvement of the corneal infiltrate. CONCLUSION: This case report demonstrates the combination of topical and systemic meropenem as a useful treatment option for corneal ulcers caused by MDR P. aeruginosa.

The role of the calcofluor white staining in the diagnosis of Acanthamoeba keratitis.

PURPOSE: Acanthamoeba keratitis is often misdiagnosed at disease onset. This study presents data to confirm the diagnosis using calcofluor white (CFW) staining. METHODS: Forty three patients were retrospectively included who presented to the Department of Ophthalmology at the University Hospital Ulm with keratitis between 2000 and 2022. Condition positive cases were diagnosed based on the typical clinical presentation of Acanthamoeba keratitis with a positive polymerase chain reaction (PCR). Condition negative were patients with ulcers due to other causing pathogens with a negative Acanthamoeba PCR result. The condition was compared with the CFW test results. RESULTS: After symptom onset, time until presentation was 17 ± 12 days and until diagnosis 27 ± 13 days in the 15 condition positive patients. Among the 35 patients with additional CFW test, 7 patients were condition positive and 28 negative. 5 of the 7 patients were true positive, 2 were false negative. In the 28 condition negative patients, 1 was false positive. Sensitivity of CFW was 71% and specificity 96%. The positive PCR results were available 3.4 ± 2.3 days after corneal scraping, the positive CFW test results on the same day in each case. CONCLUSION: Our data demonstrate that diagnosis of Acanthamoeba keratitis remains difficult and therapy is initiated late. A positive CFW test confirms the diagnosis as there are almost no false positive results and it was available faster than PCR. In case of a negative CFW test, Acanthamoeba keratitis cannot be ruled out because of a high false negative rate.

Recurrence of perforation and overall patient survival after penetrating keratoplasty versus amniotic membrane transplantation in corneal perforation.

PURPOSE: The following is a comparative analysis on the treatment outcomes of corneal perforations using amniotic membrane transplantation (AMT) or penetrating keratoplasty (PK). METHODS: This monocentric retrospective study was performed at the Department of Ophthalmology, University Hospital Ulm, Germany. A total of 78 eyes of 78 patients were included. Thirty-nine eyes received an AMT, and 39 patients were treated with a PK. Primary outcome was recurrence of perforation. Secondary outcomes were patient mortality and visual acuity. RESULTS: No statistically significant difference was observed with regard to a recurrence of perforation between the two groups (26% in AMT vs 23% in PK, p > 0.99). The time of recurrences was within the first two years and did not differ statistically (p = 0.97). In addition, a proportional hazards model with cox regression regarding recurrent perforation showed no significant differences (p = 0.5). After AMT, 41% and after KP, 28% of the patients died during follow-up (p = 0.2), respectively. The Charlson Comorbidity Index (p < 0.0001) and the age at the time of surgery (p = 0.0002) were statistically significantly higher in those who were deceased. A mean follow-up of 485 ± 517 days was recorded. CONCLUSION: Both surgical methods show good results and no statistically significant difference regarding recurrent perforation rate. About a third of the patients died during the follow-up period. The decision regarding the appropriate method should therefore be based on a combination of all factors.

Development of a drug-eluting intraocular lens to deliver epidermal growth factor receptor inhibitor gefitinib for posterior capsule opacification prophylaxis.

PURPOSE: Different molecular targets, such as the epidermal growth factor receptor, have been identified for the prophylaxis of posterior capsule opacification. This led to the proposal of several drugs, yet drug delivery into the capsular bag remains challenging. The intraocular lens as a drug delivery device would provide a convenient method to allow drug release in the location needed. This is to evaluate the effect of a drug-eluting intraocular lens using an epidermal growth factor receptor inhibitor. METHODS: Hydrophobic and hydrophilic intraocular lenses were coated with gefitinib using the dip coating technique. The cellular response on the modified intraocular lenses was tested in a human lens epithelial cell line (FHL-124) in an anterior segment model. Furthermore, modified intraocular lenses were implanted into human capsular bags ex vivo. Drug release was determined as well as the biocompatibility on human corneal endothelial cells. Unmodified intraocular lenses served as controls. In addition, immunofluorescence staining with fibronectin as a marker for fibrotic response was conducted. RESULTS: Both coated hydrophilic and hydrophobic intraocular lenses could attenuate the cell growth of FHL-124 cells in the human capsular bag in comparison to the unmodified controls. Furthermore, gefitinib-soaked intraocular lenses showed a constant drug release over the first 10 days. No reduction in cell viability of corneal endothelial cells occurred. A decrease in fibronectin expression under gefitinib treatment could be observed. CONCLUSION: In vitro epidermal growth factor receptor seems to be a valuable target for the prevention of posterior capsule opacification. The gefitinib-eluting intraocular lens in this study could inhibit cell growth in non-toxic concentrations.

Establishing an objective biomarker for corneal cystinosis using a threshold-based Spectral domain optical coherence tomography imaging algorithm.

PURPOSE: The purpose of the present study was to establish a semi-automated threshold-based image segmentation algorithm to detect and objectively quantify corneal cystine crystal deposition in ocular cystinosis with anterior segment optical coherence tomography (AS-OCT). METHODS: This prospective, observational, comparative study included 88 eyes of 45 patients from the German Cystinosis Registry Study as well as 68 eyes of 35 healthy control subjects. All eyes were imaged with AS-OCT (Cirrus HD-OCT 5000, Carl Zeiss Meditec AG, Jena, Germany). As an initial step, B-scan images were subjectively analysed for typical changes in morphology in comparison to healthy controls. Based on the experience gained, an objective semi-automated B-scan image segmentation algorithm was developed using a grey scale value-based threshold method to automatically quantify corneal crystals. RESULTS: On AS-OCT B-scans, corneal crystals appeared as hyperreflective deposits within the corneal stroma. The crystals were distributed either in all stromal layers (43 eyes, 49%) or confined to the anterior (23 eyes, 26%) or posterior stroma (22 eyes, 25%), respectively. The novel automatic B-scan image segmentation algorithm was most efficient in delineating corneal crystals at higher grey scale thresholds (e.g. 226 of a maximum of 255). Significant differences in suprathreshold grey scale pixels were observable between cystinosis patients and healthy controls (p < 0.001). In addition, the algorithm was able to detect an age-dependent depth distribution profile of crystal deposition. CONCLUSION: Objective quantification of corneal cystine crystal deposition is feasible with AS-OCT and can serve as a novel biomarker for ocular disease control and topical treatment monitoring.

Corneal optical density in Fuchs endothelial dystrophy determined by anterior segment optical coherence tomography.

PURPOSE: In this study, we propose a method to grade corneal stromal opacity using optical density measurements by anterior segment optical coherence tomography (AS-OCT) and validate the approach in Fuchs endothelial corneal dystrophy (FECD). METHODS: A retrospective analysis of human corneal OCT scans was performed on 48 eyes of 32 patients with FECD and 33 control eyes of 21 patients using the Carl Zeiss Cirrus HD-OCT 5000. In addition, corneal edema in fresh rabbit cadaver eyes was artificially induced by distilled water and imaged with the Thorlabs TELESTO-II spectral domain OCT at different time points during saturation. The increase of opacity due to corneal edema was proposed to directly correlate with enhanced reflectivity sites in the OCT images, corresponding to higher optical density. The increase was determined as the image area above a statistically established gray-scale value using ImageJ and correlated with other disease characteristics. RESULTS: Optical densities in human corneas showed significant differences between FECD patients and the control group (p = 0.002). The increased optical densities determined in FECD corneas correlated well with other disease characteristics such as corneal pachymetry or visual acuity. Likewise, rabbit corneas showed a time dependent increase in thickness and in corneal optical density during soaking in distilled water. CONCLUSION: This study presents corneal optical density by AS-OCT as an objective value for corneal changes in FECD. Complementing other diagnostic tools in FECD the assessment of corneal optical density may identify progression of FECD, gauge novel therapeutic strategies and support risk and benefit analyses for corneal surgery.

Stromal Nerve Imaging and Tracking Using Micro-Optical Coherence Tomography.

Purpose: To image, track and map the nerve fiber distribution in excised rabbit corneas over the entire stromal thickness using micro-optical coherence tomography (µOCT) to develop a screening tool for early peripheral neuropathy. Methods: Excised rabbit corneas were consecutively imaged by a custom-designed µOCT prototype and a commercial laser scanning fluorescence confocal microscope. The µOCT images with a field of view of approximately 1 × 1 mm were recorded with axial and transverse resolutions of approximately 1 µm and approximately 4 µm, respectively. In the volumetric µOCT image data, network maps of hyper-reflective, branched structures traversing different stromal compartments were segmented using semiautomatic image processing algorithms. Furthermore, the same corneas received ßIII-tubulin antibody immunostaining before digital confocal microscopy, and a comparison between µOCT image data and immunohistochemistry analysis was performed to validate the nerval origin of the tracked network structures. Results: Semiautomatic tracing of the nerves with a high range of different thicknesses was possible through the whole corneal volumes, creating a skeleton of the traced nerves. There was a good conformity between the hyper-reflective structures in the µOCT data and the stained nerval structures in the immunohistochemistry data. Conclusions: This article demonstrates nerval imaging and tracking as well as a spatial correlation between µOCT and a fluorescence corneal nerve standard for larger nerves throughout the full thickness of the cornea ex vivo. Translational Relevance: Owing to its advantageous properties, µOCT may become useful as a noncontact method for assessing nerval structures in humans to screen for early peripheral neuropathy.

Refractive Changes After Corneal Stromal Filler Injection for the Correction of Hyperopia.

PURPOSE: To evaluate a new non-ablative and adjustable procedure for laser ablative refractive corneal surgery in hyperopia using the injection of a biocompatible liquid filler material into a stromal pocket. METHODS: A total of 120 stromal pockets were created using a clinical femtosecond laser system in 96 rabbit corneoscleral discs and 24 whole globes. Pockets were cut at a depth of 120 or 250 µm below the epithelial surface. Hyaluronic acid was injected manually into the pocket. To determine the refractive changes, three-dimensional optical coherence tomography images and a specifically developed picture recognition Matlab (The Mathworks) routine were used. RESULTS: After injection, a steepening of the anterior and flattening of the posterior corneal surface was observed, which led to hyperopic correction. The two main factors determining the amount of correction were the pocket depth and the injected volume. After the pocket was homogeneously filled, an initial refractive increase was observed, followed by a linear relation between the injected volume and the refraction increase. CONCLUSIONS: This possible clinical protocol for controlled refraction correction of hyperopia suggests a potential readjustable clinical application. [J Refract Surg. 2020;36(6):406-414.].

Enhancing Rose Bengal-Photosensitized Protein Crosslinking in the Cornea.

Purpose: Rose bengal (RB)-photosensitized protein crosslinking has been proposed for several applications in the eye. This study identifies oxygen-dependent and oxygen-independent mechanistic pathways in cornea for RB-photosensitized crosslinking to enhance its efficiency for ocular treatments. Methods: Rabbit corneas ex vivo were stained with 1 mM RB and irradiated at 532 nm. RB photobleaching, measured by spectrophotometry and linear tensile strength testing, were performed with and without oxygen present. The effects of sodium azide, D2O, arginine, and ascorbate were used to discriminate between mechanisms involving energy transfer (forming singlet oxygen) and electron transfer (forming radical ions). The influence of corneal depth on RB photobleaching was determined using inclined corneal incisions. Results: RB photobleaching was greater in the presence than the absence of oxygen, enhanced by D2O and partially inhibited by azide, indicating a singlet oxygen pathway. Photobleaching without oxygen was enhanced by arginine and ascorbate and accompanied by a shift in the absorption to shorter wavelengths, suggesting that electron transfer initiates RB photodecomposition. The RB-photosensitized tensile strength increase in air was enhanced by D2O and inhibited by azide. In an O2-free environment, arginine was required for an increase in tensile strength, which matched that attained by irradiation in air without arginine, suggesting an efficient electron transfer pathway. Rapid photobleaching was observed below 80 to 120 µm only when arginine was present. Conclusions: These results indicate that RB photosensitizes crosslinking in cornea by both singlet oxygen and electron transfer mechanisms and that adding enhancers may increase the efficiency of this treatment.