Supine Positioning for Graft Attachment After Descemet Membrane Endothelial Keratoplasty: A Randomized Controlled Trial.

PURPOSE: The Supine Positioning for Descemet Membrane Endothelial Keratoplasty Attachment (SUPER-DMEK) trial assessed the efficacy of prolonged supine head positioning on graft attachment. DESIGN: Randomized controlled trial. METHODS: Participants with Fuchs' dystrophy were randomized to 5 days of supine head positioning (intervention) or to 1 day (control). Participants, surgeons, and investigators were masked until the day after surgery. Adherence to the allocated intervention was monitored using a head sensor. Main outcome measures were area and volume of graft detachment (coprimary end points) 2 weeks after surgery quantified using a validated neural network for image segmentation on anterior segment optical coherence tomography images, and repeat air injection (rebubbling), subjective visual function, and adverse events (secondary end points). RESULTS: A total of 86 participants received the allocated intervention (35 eyes intervention and 51 eyes control). In the intention-to-treat analysis, the mean area of graft detachment was 28.6% in the intervention arm and 27.5% in the control arm (adjusted between-arm difference, 1.3; 95% CI, -8.7 to 11.4; P = .80). Results for volume of detachment and as-treated analyses based on head position sensor data indicated no potentially clinically relevant effect of prolonged supine positioning on graft attachment. Results were not compatible with a relevant treatment effect on rebubbling or subjective visual function. Adverse events, most commonly back pain, were more common and more severe with the intervention. CONCLUSIONS: In this randomized controlled trial, graft attachment was not improved with prolonged supine head positioning. Prolonged supine positioning frequently caused back pain. Prolonged supine positioning after Descemet membrane endothelial keratoplasty for Fuchs' dystrophy may not be needed in routine practice.

Current Practice in the Treatment of Epithelial and Melanocytic Tumours with Interferon-α2b: A Survey of Tertiary Eye Centres in Germany.

PURPOSE: To evaluate the standard of care, in particular the use of topical or subconjunctival interferon-α2b, in treating ocular surface squamous neoplasia or melanocytic tumours in tertiary eye centres in Germany. METHODS: A survey containing 14 questions was sent to 43 tertiary eye centres in Germany. The questions addressed the surgical and medical management of ocular surface squamous neoplasia and melanocytic tumours (primary acquired melanosis and malignant melanoma), as well as the clinical experiences and difficulties in prescribing off-label interferon-α2b eye drops and subconjunctival injections. RESULTS: Twenty-four tertiary eye centres responded to the survey. Eighty-three percent of centres had used interferon-α2b in their clinical practice and 25% prescribed it as the first-line cytostatic agent following surgical excision of ocular surface squamous neoplasia, while 10% would do so for melanocytic tumours. Correspondingly, the majority of respondents selected mitomycin C as their first-line agent. Side effects were uncommon with topical interferon-α2b eye drops but were more frequently reported after subconjunctival interferon-α2b injections. In total, eight centres had experience with interferon-α2b injections. The most significant obstacles perceived by ophthalmologists when prescribing interferon-α2b were its high cost and the reimbursement thereof. CONCLUSION: Off-label mitomycin C was the preferred adjuvant therapy for epithelial and melanocytic tumours, with interferon-α2b being the standard second-line option. Interferon-α2b has predominantly been used to treat ocular surface squamous neoplasia and, to a lesser extent, melanocytic tumours at German tertiary eye centres. Following its market withdrawal, supply shortages of interferon-α2b are likely to have a profound impact on patient care and their quality of life.

Real-life data of adjuvant IFN-α2b and MMC in conjunctival melanocytic lesions.

PURPOSE: We herein compare topical interferon alpha 2b (IFN-α2b) to topical mitomycin C (MMC) in the adjuvant management after excision of primary acquired melanosis with atypia (PAM) and melanoma of the conjunctiva/cornea (CM). METHODS: We included 25 tumors from 25 patients (six with PAM and 19 with CM). After surgical excision, four patients started with adjuvant IFN-α2b (two in combination with radiotherapy), 19 with MMC, and two with radiotherapy alone. Five patients were switched from initial MMC/radiotherapy to IFN-α2b during follow-up. Efficacy was assessed via time to tumor recurrence and initial therapy response. RESULTS: With initial IFN-α2b, three patients (3/4, two with additional radiotherapy) showed complete remission (follow-up: 1478-1750 days) and one recurrence (1/4) was noted after 492 days. With initial MMC, no recurrence was recorded in 15 of the 19 patients (follow-up: 99-4732 days). Five patients were switched from MMC or radiotherapy to IFN-α2b: two patients showed complete remission (2/5), while another two (2/5) experienced recurrences and remained without recurrence after repeated courses of IFN-α2b (follow-up: 1798 and 1973 days). Only one patient showed incomplete response. Adverse effects were recorded in five patients, all received MMC. CONCLUSION: Topical IFN-α2b (arguably together with radiotherapy) may be a viable alternative to MMC in PAM and CM. We observed fewer side effects at similar response rates. However, when response to MMC was poor, IFN-α2b may also be of limited utility.

Long-Term Outcomes of Excimer Laser-Assisted Penetrating Keratoplasty Using a Commercially Available Laser System - A Retrospective Case Series.

BACKGROUND: Favorable functional outcomes have been reported after excimer laser-assisted penetrating keratoplasty (EXL PKP). But this technique has not been widely adopted, and there are reports on EXL PKP from only a very limited number of institutions. Some of these results refer to operations carried out with laser systems that are not commercially available. In this retrospective case series, we report the long-term outcome of EXL PKP using the Schwind Amaris 500E laser system. MATERIAL AND METHODS: This retrospective consecutive case series included 30 eyes of 29 patients who had undergone EXL PKP between 2010 and 2013. Primary outcome measures were topographic astigmatism and visual acuity. Secondary outcome measures were the rates of graft rejection and graft failure, and the rate of grafts with an endothelial cell density below 500 cells/mm2. Survival analyses were carried out for the following endpoints: visual acuity, rate of graft rejection, and rate of grafts with endothelial cell densities higher than 500 cells/mm2. RESULTS: The median interquartile range (IQR) duration of follow-up was 45 (36) months. The indications for PKP were keratoconus (n = 21), corneal scarring (n = 6), Fuchs endothelial dystrophy (n = 1), and corneal dystrophy other than Fuchs endothelial dystrophy (n = 2). The median (IQR) topographic astigmatism at the end of the follow-up period was 5.3 (2.9) D. Forty-five months after surgery, 73% of all eyes had a visual acuity better than 0.3 LogMAR. The rate of graft rejection after 45 months of follow-up was 32%. All eyes maintained endothelial cell densities higher than 500 cells/mm2. There was no graft failure. CONCLUSIONS: EXL PKP is a safe and effective surgical procedure. No general conclusions can be drawn on the refractive outcome of EXL PKP. Potential advantages, such as a higher degree of graft-host congruity, that could possibly improve the refractive outcome should be weighed against the higher costs of EXL PKP.

Transcriptional Profiling Provides New Insights into Organ Culture-Induced Changes in Human Donor Corneas.

Corneal transplantation is one of the most common forms of tissue transplantation worldwide. Donor corneal tissue used in transplantation is provided by eye banks, which store the tissue in culture medium after procurement. To date, the effects of cell culture on human corneal tissue have not been fully elucidated. Using the 3' RNA sequencing method for massive analysis of cDNA ends (MACE), we show that cultivation of corneal tissue leads to significant changes in a variety of molecular processes in human corneal tissue that go well beyond aspects of previously known culture effects. Functionally grouped network analysis revealed nine major groups of biological processes that were affected by corneal organ culture, among them keratinization, hypoxia, and angiogenesis, with genes from each group being affected by culture time. A cell type deconvolution analysis revealed significant modulations of the corneal immune cell profile in a time dependent manner. The results suggest that current culture conditions should be further refined and that prolonged cultivation may be detrimental. Recently, we showed that MACE enables transcriptional profiling of formalin-fixed and paraffin-embedded (FFPE) conjunctival tissue with high accuracy even after more than 10 years of storage. Here we demonstrate that MACE provides comparable results for native and FFPE corneal tissue, confirming that the technology is suitable for transcriptome analysis of a wide range of archived diseased corneal samples stored in histological archives. Finally, our data underscore the feasibility of bioinformatics cell-type enrichment analysis in bulk RNA-seq data to profile immune cell composition in fixed and archived corneal tissue samples, for which RNA-seq analysis of individual cells is often not possible.

Corneal Oedema: Aetiology, Diagnostic Testing, and Treatment.

Corneal oedema results from an underlying pathology, which can be diverse in origin, and may be mechanical, dystrophic, or inflammatory, and affect any layer of the cornea. Diagnostic tools such as Scheimpflug imaging and anterior segment optical coherence tomography have standardised quantification of corneal oedema and have become important aids in clinical practice. Timely diagnosis and treatment are key to preventing irreversible damage to the corneal ultrastructure, such as anterior corneal fibrosis or endothelial cell damage. The oedema usually resolves quickly when the underlying cause has been addressed. Symptomatic treatment using hyperosmolar agents has failed to show any benefits in oedema resolution or improvement in visual acuity compared to placebo. In contrast, rho-associated protein kinase (ROCK) inhibitors offer a promising option for medical treatment in cases of endothelial dysfunction, but their safety and efficacy must be further validated in large scale clinical trials. Until then, endothelial or penetrating keratoplasties remain the mainstay treatment where structural changes to the cornea have occurred.

Impairment of Vestibular Function and Balance Control in Patients with Type 2 Diabetes.

BACKGROUND: Recent evidence suggests that falls are a major complication of diabetes in elderly patients, leading to disability and preventable death. However, the potential risk factors leading to falls in patients with type 2 diabetes are not fully understood. This study was designed to explore the characteristics of vestibular dysfunction and balance control in patients with type 2 diabetes and to analyse the risk factors associated with falls. METHODS: The study recruited 51 patients with type 2 diabetes and 43 controls who underwent vestibular function tests and balance control capability tests between January 2013 and December 2015. Vestibular function and balance control capability assessment was based on slow-phase velocity, canal paresis, Sensory Organisation Test (SOT) score, Limits of Stability Test (LOS) score, and Motor Control Test (MCT) score. RESULTS: In all, 56.7% of the diabetic patients had vestibular dysfunction, compared with 27.9% of the controls (p = 0.005). Vestibular dysfunction was dependent on the duration of the disease and serum HbA1c levels. There were no significant differences between the two groups with respect to the balance test results for SOT score, somatosensory subtest score, vestibular subtest score, or LOS score. However, the visual system and MCT scores were significantly lower in the diabetic patients than in the controls (p = 0.032 and p = 0.018, respectively). CONCLUSIONS: Patients with type 2 diabetes have a higher incidence of vestibular dysfunction. Vestibular dysfunction, visual system impairment, and a decline in motion control may be the risk factors that can lead to falls, and thus need to be managed accordingly in diabetic patients.