Collagen Cross-Linking: Current Status and Future Directions

Collagen cross-linking (CXL) using UVA light and riboflavin (vitamin B2) was introduced as a clinical application to stabilize the cornea by inducing cross-links within and between collagen fibers. CXL has been investigated extensively and has been shown clinically to arrest the progression of keratoconic or post-LASIK ectasia. With its minimal cost, simplicity, and proven positive clinical outcome, CXL can be regarded as a useful approach to reduce the number of penetrating keratoplasties performed. Small case series have also indicated that CXL is beneficial in corneal edema by reducing stromal swelling behavior and in keratitis by inhibiting pathogen growth. Despite these encouraging results, CXL remains a relatively new method that is potentially associated with complications. Aspects such as side effects and recurrence rates have still to be elucidated. In light of the growing interest in CXL, our paper summarizes present knowledge about this promising approach. We have intentionally endeavored to include the more relevant studies from the recent literature to provide an overview of the current status of CXL

Subjective and objective accommodation of the Crystalens Advanced Optics (AO) in patients 6 months after bilateral implantation

Background: The aim of this study was to analyze and compare objective and subjective accommodation in patients after bilateral implantation of the FDA-approved accommodating Crystalens Advanced Optics (AO). Material and methods: This study was performed on 8 eyes of 4 patients. The subjective accommodation was measured by monocular and binocular defocus curves under photopic and mesopic conditions. The objective accommodation was analyzed using partial coherence interferometry (PCI) and wavefront aberration. Pupil diameter at different set-ups and refraction were derived from wavefront data. Results: Uncorrected and corrected distance and uncorrected near visual acuity improved significantly following implantation of the Crystalens AO in all eyes. Only one patient needed spectacles to correct distance visual acuity. Mean distance uncorrected visual acuity was 0.05 ± 0.06 logMAR. All patients were able to read newspapers without spectacles. Mean near uncorrected visual acuity was 0.17 ± 0.12 logMAR. Subjective accommodative amplitude under photopic conditions was significantly better binocularly than monocularly (p = 0.03) and was significant worse monocularly under mesopic conditions than photopic conditions (p = 0.016). No significant changes in anterior chamber depth were observed by PCI, with a fixation on optical stimuli at different distances. There were also no significant changes in the wavefront aberrations between the different set-ups. Pupil diameter increased significantly in the near set-up under mesopic conditions. Conclusions: No objective change in lens configuration was observed under different set-ups. Due to a variety of factors involved in pseudoaccommodation (e.g. pupil diameter, astigmatism, and multifocality), the subjective accommodative amplitude tends to be overestimated relative to objective measurements. No real accommodative action was observed

Clinical Study Results after En Bloc Lateral Wall Decompression Surgery with Orbital Fat Resection in 111 Patients with Graves' Orbitopathy

properly cited. Purpose. To evaluate the effect of en bloc lateral wall decompression with additional orbital fat resection in terms of exophthalmos reduction and complications. Methods. A retrospective, noncomparative case series study from 1999 to 2011 (chart review) in Graves' orbitopathy (GO) patients. The standardized surgical technique involved removal of the lateral orbital wall including the orbital rim via a lid crease approach combined with additional orbital fat resection. Exophthalmos, diplopia, retrobulbar pressure sensation, and complications were analyzed pre-and postoperatively. Results. A total of 111 patients (164 orbits) with follow-up >3 months were analysed. Mean exophthalmos reduction was 3.05mm and preoperative orbital pressure sensation resolved or improved in all patients. Visual acuity improved significantly in patients undergoing surgery for rehabilitative or vision threatening purposes. Preoperative diplopia improved in 10 patients (9.0%) but worsened in 5 patients (4.5%), necessitating surgical correction in 3 patients. There were no significant complications; however, one patient had slight hollowing of the temporalis muscle around the scar that did not necessitate revision, and another patient with a circumscribed retraction of the scar itself underwent surgical correction. Conclusions. The study confirms the efficiency of en bloc lateral wall decompression in GO in a large series of patients, highlighting the low risk of disturbance of binocular functions and of cosmetic blemish in the temporal midface region

Corneal Subbasal Nerve Plexus Changes in Severe Diabetic Charcot Foot Deformity: A Pilot Study in Search for a DNOAP Biomarker

Introduction. Diabetic neuroosteoarthropathy (DNOAP) early symptoms are unspecific, mimicking general infectious symptoms and rendering a diagnosis challenging. Consequently, unfavourable outcomes occur frequently, with recurrent foot ulceration, infectious complications, and eventually amputation. Corneal confocal microscopy (CCM) of the subbasal nerve plexus (SNP) is used to detect early peripheral neuropathy in diabetic patients without diabetic retinopathy. This pilot study was designed to determine if specific SNP changes manifest in severe DNOAP in comparison to a healthy control group. Methods. This pilot study utilized a matched-pair analysis to investigate SNP changes by in vivo CCM for 26 patients (mean patient age 63.7 years, range 27 to 78) with severe DNOAP defined by condition after the need for reconstructive foot surgery (n=13) and a healthy control group (n=13). Corneal nerve fibre length (CNFL), nerve fibre density (CNFD), nerve branch density (CNBD), average weighted corneal nerve fibre thickness (CNFTh), nerve connecting points (CNCP), and average weighted corneal nerve fibre tortuosity (CNFTo) were assessed as well as the general clinical status, diabetic status, and ophthalmologic basic criteria. Results. In vivo CCM revealed significantly reduced SNP parameters in the DNOAP group for CNFL (p=0.010), CNFD (p=0.037), CNBD (p=0.049), and CNCP (p=0.012) when compared to the healthy control group. Six patients (46%) of the DNOAP group suffered from diabetic retinopathy and none of the control group. Conclusions. This pilot study revealed a rarefication of SNP in all measured parameters in patients with severe DNOAP. We see a potential value of CCM providing a SNP-based biomarker for early stages of DNOAP prior to the development of any foot deformities that needs to be evaluated in further studies. This trial is registered with German Clinical Trials Register (DKRS) DRKS00007537

Burst of corneal dendritic cells during Trastuzumab and Paclitaxel treatment

During breast cancer therapy, paclitaxel and trastuzumab are both associated with adverse effects such as chemotherapy-induced peripheral neuropathy and other systemic side effects including ocular complications. Corneal nerves are considered part of the peripheral nervous system and can be imaged non-invasively by confocal laser scanning microscopy (CLSM) on the cellular level. Thus, in vivo CLSM imaging of structures of the corneal subbasal nerve plexus (SNP) such as sensory nerves or dendritic cells (DCs) can be a powerful tool for the assessment of corneal complications during cancer treatment. During the present study, the SNP of a breast cancer patient was analyzed over time by using large-scale in vivo CLSM in the course of paclitaxel and trastuzumab therapy. The same corneal regions could be re-identified over time. While the subbasal nerve morphology did not alter significantly, a change in dendritic cell density and an additional local burst within the first 11 weeks of therapy was detected, indicating treatment-mediated corneal inflammatory processes. Ocular structures such as nerves and dendritic cells could represent useful biomarkers for the assessment of ocular adverse effects during cancer therapy and their management, leading to a better visual prognosis

Mosaic vs. Single Image Analysis with Confocal Microscopy of the Corneal Nerve Plexus for Diagnosis of Early Diabetic Peripheral Neuropathy

The assessment of the corneal nerve fibre plexus with corneal confocal microscopy (CCM) is an upcoming but still experimental method in the diagnosis of early stage diabetic peripheral neuropathy (DPN). Using an innovative imaging technique—Heidelberg Retina Tomograph equipped with the Rostock Cornea Module (HRT-RCM) and EyeGuidance module (EG)—we were able to look at greater areas of subbasal nerve plexus (SNP) in order to increase the diagnostic accuracy. The aim of our study was to evaluate the usefulness of EG instead of single image analysis in diagnosis of early stage DPN

Real-time large-area imaging of the corneal subbasal nerve plexus

The morphometric assessment of the corneal subbasal nerve plexus (SNP) by confocal microscopy holds great potential as a sensitive biomarker for various ocular and systemic conditions and diseases. Automated wide-field montages (or large-area mosaic images) of the SNP provide an opportunity to overcome the limited field of view of the available imaging systems without the need for manual, subjective image selection for morphometric characterization. However, current wide-field montaging solutions usually calculate the mosaic image after the examination session, without a reliable means for the clinician to predict or estimate the resulting mosaic image quality during the examination. This contribution describes a novel approach for a real-time creation and visualization of a mosaic image of the SNP that facilitates an informed evaluation of the quality of the acquired image data immediately at the time of recording. In cases of insufficient data quality, the examination can be aborted and repeated immediately, while the patient is still at the microscope. Online mosaicking also offers the chance to identify an overlap of the imaged tissue region with previous SNP mosaic images, which can be particularly advantageous for follow-up examinations

In vivo monitoring of corneal dendritic cells in the subbasal nerve plexus during Trastuzumab and Paclitaxel breast cancer therapy - a one-year follow-up

Paclitaxel and trastuzumab have been associated with adverse effects including chemotherapy-induced peripheral neuropathy (CIPN) or ocular complications. In vivo confocal laser scanning microscopy (CLSM) of the cornea could be suitable for assessing side effects since the cornea is susceptible to, i.e., neurotoxic stimuli. The study represents a one-year follow-up of a breast cancer patient including large-area in vivo CLSM of the subbasal nerve plexus (SNP), nerve function testing, and questionnaires during paclitaxel and trastuzumab therapy. Six monitoring sessions (one baseline, four during, and one after therapy) over 58 weeks were carried out. Large-area mosaics of the SNP were generated, and identical regions within all sessions were assigned. While corneal nerve morphology did not cause alterations, the number of dendritic cells (DCs) showed dynamic changes with a local burst at 11 weeks after baseline. Simultaneously, paclitaxel treatment was terminated due to side effects, which, together with DCs, returned to normal levels as the therapy progressed. Longitudinal in vivo CLSM of the SNP could complement routine examinations and be helpful to generate a comprehensive clinical picture. The applied techniques, with corneal structures acting as biomarkers could represent a diagnostic tool for the objective assessment of the severity of adverse events and the outcome