Esben Nielsen

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Purpose: The primary goal was to validate a Danish translated version of the Catquest‐9SF by Rasch analysis. The secondary goal was to investigate whether preoperative Catquest‐9SF scores, best‐corrected visual acuity, comorbidity, gender, age or corneal astigmatism could predict improvements in subjective outcome.Methods: In a prospective trial, 250 patients eligible for cataract surgery were included. Patients filled out the translated Catquest‐9SF questionnaire before surgery and again 3 months after surgery. Both preoperative and postoperative questionnaires were included in the Rasch analysis. A multiple reverse stepwise regression model was used to investigate the correlation between preoperative measurements and subjective improvement.Results: The preliminary Rasch analysis showed misfit of items 4 and 6. These items were removed, and the remaining seven items demonstrated a measurement precision of 2.78, a person reliability coefficient of 0.89, ordered response categories, infit of 0.69–1.22, outfit of 0.73–1.14, observed raw variance explained by measures of 70.4% and an eigenvalue of 1.7. Item 7 showed a mild DIF for gender (0.54 logits), and person mean Rasch score targeting was −1.69 logits. Preoperative Catquest score was the only parameter with a significant correlation to a gain in subjective outcome (p < 0.001). A preoperative Catquest‐9SF score of 0.5 carried a 95% likelihood of an increase in subjective outcome.Conclusion: The Danish version of the Catquest‐9SF fit the Rasch model. Only preoperative Catquest‐9SF score was correlated to subjective improvement, and a cut‐off value of 0.5 predicted an improvement in subjective outcome with 95% probability.

Purpose: To investigate the determining factors of vision and subjective outcome after Descemet's stripping automated endothelial keratoplasty (DSAEK) for Fuchs’ endothelial dystrophy (FECD).Methods: In a prospective study, 41 FECD patients who received DSAEK were compared to 40 cataract patients with normal corneas who received cataract surgery (control group). Subjects were recruited between March 2013 and July 2014. Observational procedures included the following: best‐corrected visual acuity (BCVA), contrast sensitivity (CS), Catquest‐9SF questionnaire, Scheimpflug tomography and anterior OCT. Examinations were carried out before surgery and at 3‐, 6‐ and 12‐month follow‐up. Main outcome measures were associations between corneal optics and visual parameters, as well as subjective improvement (Catquest‐9SF effect size)Results: Best‐corrected visual acuity (BCVA) negatively correlated with anterior higher‐order aberrations (HOA's) (p < 0.001) and central corneal thickness (p = 0.001). Contrast sensitivity (CS) was negatively correlated with anterior HOA's (p = 0.002) and positively correlated with posterior densitometry (p = 0.008). Catquest‐9SF effect size was 1.32 (CI: 1.0–1.6) in the control group, 1.84 (CI: 1.4–2.3) in FECD patients who received phacoemulsification and intra‐ocular lens implantation in combination with DSAEK (n = 26) and 1.37 (CI: 0.6–2.1) in pseudophakic FECD patients who received DSAEK (n = 15).Conclusions: DSAEK surgery leads to considerable improvement in patient‐reported outcome in FECD patients. There was a strong correlation between anterior HOA's and vision after DSAEK, suggesting that anterior corneal pathology constitutes the major limitation for visual recovery after DSAEK.

To evaluate the endothelial pump function in vivo after Descemet stripping automated endothelial keratoplasty (DSAEK). In a prospective controlled trial, a group of 17 patients with Fuchs endothelial corneal dystrophy (FECD) eligible for DSAEK surgery and a group of 15 patients with cataract but with normal corneas eligible for cataract surgery (controls) were formed. A low oxygen-permeable contact lens was used to induce corneal edema. Changes in central corneal thickness were monitored as an indirect measure of endothelial cell pump function. Experiments were performed before surgery and repeated 12 months after surgery. Comparing the FECD and control groups before surgery, there was 24.8% (13.5-36.1) more edema in the FECD group after 2 hours (P < 0.001) and 19.9% (8.6-31.3) more edema in the FECD group after 3 hours (P < 0.001). In the FECD group, there was 15% (3.1-26.9) less edema after DSAEK than before surgery (P = 0.015) after 3 hours. Comparing the DSAEK-treated eyes with the control eyes 12 months after surgery; there was 12.8% (3.5-22.1) more edema in the DSAEK group after 2 hours (P = 0.007), but after 3 hours, the percentages of edema were similar (P = 0.11). Twelve months after DSAEK surgery, the grafted endothelium cleared the induced edema as fast as the control group, indicating a viable and near-normal endothelial pump function. However, significant differences in the deswelling patterns were detected, which may be caused by the added corneal stroma after DSAEK.

Purpose: The purpose of this study was to investigate the pathophysiologic heterogeneity of Fuchs endothelial corneal dystrophy (FECD). Methods: We conducted a systematic immunofluorescence study on 39 Descemet membrane samples from FECD patients and compared these with 10 Descemet membrane samples from patients with pseudophakic bullous keratopathy (PBK) and 7 normal corneas. Samples were analyzed with immunofluorescence using antibodies to the α₁-chain [collagen VIII α₁-chain (COL8A1)] and α₂-chain (COL8A2). Intensity of staining was assessed using a subjective grading scale from 0 to 3. The presence of specific staining patterns was noted. Results: The overall distribution of COL8A1 staining intensity between groups was significantly different (P = 0.002). There was marked/intense staining in 85% (33/39) of the FECD samples, 40% (4/10) of the PBK samples (P = 0.034), and 29% (2/7) of normal samples (P = 0.004). The overall distribution of COL8A2 staining intensity was not significantly different between groups (P = 0.39). There was marked/intense staining in 33% (13/39) of the FECD samples, 10% (1/10) of PBK samples, and 14% (1/7) of the normal samples. There was substantial variation in staining intensity in the FECD group, a phenomenon that was especially pronounced for the COL8A2 antibody. Conclusions: We found increased staining for COL8A1, but not COL8A2 in FECD samples. Further, there was striking variation of staining intensity in FECD patients, indicating pathophysiological heterogeneity.

Fuchs endothelial corneal dystrophy (FECD), is the most common corneal endothelial dystrophy, and contributes up to 50% of all corneal transplantations performed in developed countries. FECD develops in Descemet’s membrane (DM) and possibly alters the mechanical properties and internal structures in this basal lamina. In this work, the morphology and mechanical properties of FECD-DMs are studied by transmission electron microscopy (TEM) and quantitative dynamic atomic force microscopy (QD-AFM) at nano scale. Pathological wide-space collagens that are typical of FECD display different mechanical properties in that they are softer than the remaining tissue both for dehydrated- and fully hydrated samples. Additionally, the hydration level has major influence on the mechanical properties. These findings could help to further understand the structural changes in FECD, and possibly be useful for further characterization of the disease, the diagnosis and assessment or even pathologic analysis.

More than 60 mutations in transforming growth factor beta‐induced protein (TGFBIp) have been reported in humans causing a variety of phenotypic protein aggregates in the cornea, commonly termed corneal dystrophies. One mutation, generating an arginine to histidine amino acid substitution at position 124 in mature TGFBIp leads to granular corneal dystrophy type 2 (GCD2). Homozygous GCD2 cases develop massive protein accumulation early in life whereas heterozygous GCD2 cases become affected much later and generally with a much less severe outcome. However, if heterozygous GCD2 patients undergo laser‐assisted in situ keratomileusis (LASIK) surgery protein accumulation is accelerated and they develop massive protein accumulations a few years after surgery. Here, we present the protein profile of aggregate‐containing corneal tissue from GCD2 patients with a history of LASIK surgery using LC–MS/MS. Label‐free quantification of corneal extracellular matrix proteins showed accumulation of TGFBIp. This was supported by 2DE and immunoblotting against TGFBIp that revealed the accumulation of full‐length TGFBIp. In addition, a high molecular weight TGFBIp complex was more apparent in GCD2 patients after LASIK surgery, which may be important for the disease progression. Lastly, 2DE also revealed differential processing between GCD2 patients with a history of LASIK surgery when compared to healthy individuals.

Purpose: Fungal keratitis is a severe sight‐threatening condition. The aim of this study was to investigate the incidence and clinical characteristics of fungal keratitis patients living in a temperate climate.Methods: By reviewing medical records from 2000 to July 2013, patients with fungal keratitis were identified. Risk factors, clinical signs and outcome were registered.Results: Twenty‐five patients were identified: 52% with Candida, 20% with Fusarium, 16% with Aspergillus and 12% with mixed filamentous fungi. A minimum incidence of fungal keratitis of 0.6 cases per million per year was estimated. Prior topical steroid treatment was commonly found in our cases (44%). Trauma including contact lens wear was associated with infection with filamentous fungi, whereas in patients with Candida infection, ocular surface disease was a prominent feature. Median time from onset of symptoms to diagnosis was 24 days. Only a few patients exhibited classical clinical features such as endothelial plaques (28%), satellite lesions (24%) and feathery edges (16%). The final visual outcome was poor with an average best‐corrected logMAR of (mean, 95% CI) 0.70 (0.4–1.0). A total of 52% were treated with corneal transplantation. Patients with Candida infections had a significantly worse visual outcome.Conclusion: We found that patients with fungal keratitis had a poor visual outcome. However, knowledge of risk factors and clinical signs leading to early treatment can improve the prognosis.

Purpose: Introducing a simple image grading system to support the interpretation of in vivo confocal microscopy (IVCM) images in filamentous fungal keratitis. Setting: Clinical and confocal studies took place at the Department of Ophthalmology, Aarhus University Hospital, Denmark. Histopathological analysis was performed at the Eye Pathology Institute, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark. Methods: A recent series of consecutive patients with filamentous fungal keratitis is presented to demonstrate the results from in-house IVCM. Based upon our experience with IVCM and previously published images, we composed a grading system for interpreting IVCM images of filamentous fungal keratitis. Results: A recent case series of filamentous fungal keratitis from 2011 to 2012 was examined. There were 3 male and 3 female patients. Mean age was 44.5 years (range 12-69), 6 out of 17 (35%) cultures were positive and a total of 6/7 (86%) IVCM scans were positive. Three different categories of IVCM results for the grading of diagnostic certainty were formed. Conclusion: IVCM is a valuable tool for diagnosing filamentous fungal keratitis. In order to improve the reliability of IVCM, we suggest implementing a simple and clinically applicable grading system for aiding the interpretation of IVCM images of filamentous fungal keratitis.