Keratometry Changes Between Year One to Seven After Corneal Cross-Linking in Patients With Keratoconus.

PURPOSE: We evaluated the timing at and extent to which midterm to long-term keratometric changes can occur in year 1 to 7 after corneal collagen cross-linking (CXL) in patients with keratoconus. METHODS: We conducted a subgroup analysis of a retrospective cohort study of all consecutive patients who underwent CXL at our cornea center between 2007 and 2011. The inclusion criteria comprised CXL according to the Dresden protocol and a full set of keratometry parameters collected by Scheimpflug tomography preoperatively and at year 1, 3, 5, and 7 after CXL. In addition, best-corrected visual acuity was evaluated. RESULTS: Sixty-three eyes of 47 patients were enrolled. Mean age was 25.46 years ±7.39 years (80.9% male patients). All relevant keratometric parameters showed significant improvement at year 1 after CXL (except for posterior astigmatism). According to mixed-effects model analysis, they all showed further significant change at different points in time between year 1, 3, 5, and 7 (except for K1). In addition, best-corrected visual acuity improved statistically significant between year 1, 3, 5, and 7. Suspected disease progression was noted in 22.2% of patients, mostly between year 1 and 3 after CXL. CONCLUSIONS: After initial improvement 1 year after CXL, keratometric and functional parameters were stable until year 5 after CXL in most cases; further improvement can take place even after up to 7 years post-CXL. By contrast, in case of disease progression, changes seem to occur already between year 1 and 3 after CXL.

Hertel-exophthalmometry-like multi-detector-row-CT-exophthalmometry: inter-disciplinary inter-observer reproducibility of measurements.

OBJECTIVES: To investigate the interdisciplinary interobserver reproducibility of Hertel-exophthalmometry-like protrusion measurements on multidetector-row-computed-tomography- (MDCT-) images of the orbit to facilitate structured evaluation of the orbit and mid-face. METHODS: Respective reproducibility of base-length along the interfronto-zygomatic line, right and left ocular protrusion, and deriving interocular difference was measured in this retrospective (04/2009-03/2020) single-centre observational study. MDCT-series and slice-positions were selected independently, using picture-archiving-and-communication-system- (PACS-) tools on tilt-corrected axial MDCT-images (slice-thickness 0.6-3.0 mm, window/centre 350/50 HU) in 37 selected adult patients (24 female, age 57 ± 13 years, average±standard-deviation) with clinical indication for Hertel-exophthalmometry, by one radiology-attending, two ophthalmology-attendings, one critical-care-attending, and one ear-nose-throat-surgery resident, respectively. Bland-Altman plots and Wilcoxon-matched-pairs-signed-rank-tests compared interobserver results. RESULTS: Mean and median interobserver and intraobserver (radiology-attending) deviations were within 1 mm of respective averages of base-length (98 ± 4 mm), right and left ocular protrusion (21 ± 4 mm) and interocular difference (2 ± 1 mm). Relative interobserver deviations were within 2.0% of average (all patients) for base-length, and 5.0% (>80% of patients) for ocular protrusion. Pairwise interobserver comparison showed no significant differences between interocular differences of protrusion. CONCLUSIONS: Respective measurements of base-length, ocular protrusion, and deriving interocular difference show high interdisciplinary interobserver reproducibility in tilt-corrected axial MDCT-images of the orbit or mid-face. ADVANCES IN KNOWLEDGE: Hertel-exophthalmometry-like protrusion measurements did not depend on the years of experience or the medical subspecialty of the observer. Measurements are objective, well reproducible and important for multiple medical disciplines and should thus be included in pertinent radiology reports.

[Thyroid Eye Disease-Compressive Optic Neuropathy]. / Optikuskompression bei endokriner Orbitopathie.

BACKGROUND: The aim of this study was to evaluate the functional outcomes in terms of best-corrected visual acuity (BCVA) and visual field (VF) defects in optic nerve compression (thyroid eye disease-compressive optic neuropathy, TED-CON) patients after treatment. PATIENTS AND METHODS: In this observational, retrospective study, the medical charts of 51 patients (96 eyes) with a diagnosis of definitive TED-CON between 2010-2020 were included. RESULTS: After the diagnosis of TED-CON, 16 patients (27 eyes) received steroid-pulse (medical) treatment alone, 67 eyes received an additional surgical orbital decompression, whereas 1 patient (2 eyes) refused both treatment methods. In 74 eyes (77.1%) we detected an improvement of the BCVA ≥ 2 lines after the treatment over a mean time interval of 31.7 weeks (with no significant difference between treatment methods). In 22 eyes (27.2%) out of the 81 that underwent a posttreatment VF examination, we observed a complete resolution of the defects over a mean time interval of 39.9 weeks. When we limited analysis to patients with a minimum follow-up of 6 months at last visit, we found 33 eyes (61.1%) out of 54 eyes still had a VF defect. CONCLUSION: In our data, more than half of the TED-CON cases (61.5%) had a good prognosis with a final BCVA ≥ 0.8  at the last visit; however, only 22 eyes (27.2%) showed a complete resolution of VF defects, while 33 eyes (61.1%) had residual defects measured after a minimum follow-up of 6 months. These results suggest that while the BCVA recovers relatively well, the VF of patients is likely to remain marked by optic nerve compression.

Corneal cross-linking in patients with keratoconus: up to 13 years of follow-up.

INTRODUCTION: To evaluate long-term safety and efficacy of corneal collagen cross-linking (CXL) in patients with keratoconus up to 13 years. MATERIALS AND METHODS: In this mono-centre exploratory study, we included all consecutive patients who underwent CXL in our cornea centre from 01/01/2007 to 12/30/2011 and met the inclusion criteria. CXL was performed in all patients according to the Dresden protocol. Evaluation included best-corrected visual acuity (BCVA), topographic keratometry by Scheimpflug corneal tomography and endothelial cell count (ECC). Follow-up measurements were taken up to 13 years after treatment were compared with baseline values. RESULTS: The study enrolled 168 eyes. The mean age of our patients was 26.3 years ± 7.8 years. A complete topographic dataset was available 1 year postoperatively for 142 eyes, 5 years postoperatively for 105 eyes, 10 years postoperatively for 61 eyes and 13 years postoperatively for 9 eyes. BCVA increased statistically significant after 1 year, 5 years and 10 years and non-significantly after 13 years. All keratometric parameters with exception of posterior astigmatism showed a statistically significant decrease after 1 year, 5 years and 10 years. After 13 years, the decrease was statistically significant only in Kmax, K2 and thinnest cornea. No significant changes in ECC were detected. Three eyes received Re-CXL, none of the eyes received penetrating keratoplasty and no infections occurred in this cohort. CONCLUSIONS: CXL can slow down or even stop the progression of keratoconus in the majority of cases. The effect is long-lasting with excellent safety.

A prospective randomized pilot study evaluating the scar outcome after gluteal dermis fat graft with and without kinesiotaping.

PURPOSE: To compare gluteal wound healing after dermis fat graft (DFG) implantation in patients with and without local application of kinesiotapes. METHODS: In this prospective, single-center analysis, 16 patients who underwent DFG implantation were randomized in two groups. Wound healing was compared 4-6 weeks after therapy and 3 months later (after application of 2 cycles of kinesiotaping for 2-3 weeks in the case and no specific therapy in the control group). Demographic data, patient content and wound healing were assessed. Scarring was graded (0-3) by evaluation of photodocumentation by 2 blinded, independent observers. RESULTS: Mean scar grading by both observers decreased from 2.31 ± 0.48 to 1.13 ± 0.72 in the case and from 2.38 ± 0.52 to 1.44 ± 0.50 in the control group with interobserver agreement on scar grading being substantial to almost perfect in both groups. Scar length decreased significantly in both groups (p = 0.008). Scar prominence decreased in 2/3 of cases in the case and 1/3 in the control group. Scar coloring significantly improved in the case group alone (p = 0.031). CONCLUSION: No functionally impairing or painful scar developed. No adverse effects occurred after kinesiotaping. Gluteal scars shortened significantly over time and were significantly paler in the case group. Kinesiotaping may improve scar elevation over no specific scar therapy.

Epidemiological characteristics and clinical course of eyelid squamous cell carcinoma patients from a large tertiary centre between 2009 and 2020.

BACKGROUND/AIMS: To assess epidemiological tumour features, risk factors, clinical management and outcome of eyelid squamous cell carcinoma (SCC) and changes thereof. Furthermore, we searched for validating predictors of the American Joint Committee on Cancer (AJCC) 8 classification system. METHODS: We evaluated data of 117 patients with histologically proven eyelid SCC at a large tertiary German university centre between January 2009 and March 2020. This retrospective, monocentric analysis included descriptive statistics and non-parametric tests (p<0.05). RESULTS: Histologically controlled excision and follow-up was performed in 88 (75.2%) patients. In the remaining patients with higher T-category, individual adjuvant therapy combinations were initiated. We found higher numbers of nodal metastasis and recurrence for male patients and higher T-category (p=0.035, p=0.008 and p=0.001, p<0.001). Recurrence rates proved higher for patients with multiple lesions (p=0.008). Disease-specific survival (DSS) was 95.7% at 2 and 94.9% at 5 years of follow-up. Six patients (5.1%) died from eyelid SCC with nodal metastasis and higher T-category being negative prognostic factors (p<0.001 and p=0.009). Mortality was associated with tumour location in the medial upper eyelid, nodal metastasis being more frequent (p=0.001 and p=0.009) and tumour of the lower eyelid alone as positive predictor (p=0.012). T category differed in 34 (29.1%) patients when comparing AJCC 7 and 8 (p<0.001). Changes in T category as per the AJCC 8 classification resulted in better prediction of DSS (p=0.024). CONCLUSION: Special attention should be paid to male patients, tumour location in the upper medial eyelid and lymph node diagnostics. Prediction of DSS proved superior as per the AJCC 8 staging system.

Evaluating the interreader agreement and intrareader reproducibility of Visual Field Defects in Thyroid Eye Disease- Compressive Optic Neuropathy.

PURPOSE: To categorize visual field (VF) defects according to Freitag and Tanking's (FT) classification in Thyroid Eye Disease-Compressive Optic Neuropathy (TED-CON) and evaluate the interreader agreement and intrareader reproducibility of the classification. SUBJECTS AND METHODS: In this retrospective, observational study we included medical reports of 96 eyes (51 patients), who underwent VF testing with TED-CON in Ludwig-Maximilians-University (2008-2019). Two readers separately examined the VFs at the time of the TED-CON diagnosis, each offering two readings of the same VF in a time interval of 1 month. None of our patients were diagnosed with only VF testing. The visual field testing was only performed when the inclusion criteria for TED-CON were met. RESULTS: The most common VF defects upon TED-CON diagnosis were stage 1b defects in FT classification (34.4% for reader 1, 35.4% for reader 2), followed by stage 2b (10.4% for reader 1, 14.6% for reader 2), and stage 3 (10.4% for both readers). The overall interreader agreement between 2 examiners was substantial for the first reading (69.8% agreement, kappa 0.635 (95% CI [0.525-0.745])) and moderate for the second reading (66.7% agreement, kappa 0.598 (95% CI [0.488-0.708])). The intrareader reproducibility ranged from substantial to almost perfect (78.1% agreement) between readings (kappa 0.736 (95%CI [0.638-0.834])) for reader 1 and 90.6% agreement (kappa 0.885 (95%CI [0.814-0.956])) for reader 2. CONCLUSION: We found good BCVA (LogMAR ≤ 0.2), in nearly half of the cases (44 eyes, 45.8%) and also, strikingly near perfect visual acuity (BCVA LogMAR ≤0.1) in 22.9% of the cases (22 eyes) with TED-CON. We conclude that clinicians should be alert to VF defects in the inferior region (stage 1a/1b in the FT classification) even in patients with a good BCVA.

A pathological indicator for dysthyroid optic neuropathy: tritan color vision deficiency.

PURPOSE: To investigate the sensitivity of the color vision test by Arden in patients with dysthyroid optic neuropathy (DON) to improve diagnosis. METHODS: In this observational, retrospective study, we included the medical records of 92 eyes (48 patients) with diagnosis of DON between 2008 and 2019 in order to evaluate the full spectrum of findings from the color vision test by Arden, and to determine potential importance of this test. Thirty-five patients were female, and 13 patients were male. The mean age was 58.0 years (range: 34-79) at the time of the DON diagnosis. RESULTS: Forty-one eyes displayed relatively good BCVA with ≤ 0.2 LogMAR. We found a protan value exceeding the threshold of ≥ 8% in 57 eyes (30 patients) at the time of the diagnosis. The sensitivity of protan was 61.9% (95% CI 51.2-71.8%), while that of tritan was a striking 98.9% (95% CI 94.1-99.9%). We discovered one pathological sign, tritan deficiency (based on a threshold of ≥ 8%) consistently in all eyes but one at the time of the diagnosis, regardless of the visual field defects or any changes in best-corrected visual acuity (BCVA). CONCLUSION: We found blue-yellow (tritan) deficiency, to be a sensitive and reliable indicator of dysthyroid optic neuropathy. We conclude that, in cases with suspected DON, a color vision test that can detect tritan deficiency is an essential tool for the adequate assessment, diagnosis, and treatment of DON.

Morphologic Cross-Sectional Imaging Features of IgG4-Related Orbitopathy in Comparison to Ocular Adnexal Lymphoma.

AIM: To detect radiological features that, in addition to clinical findings, may aid in correct differentiation between IgG4-related ophthalmic disease (IgG4-ROD) and ocular adnexal lymphoma (OAL). METHODS: In this retrospective, single-center, comparative analysis, we compared cross-sectional imaging findings of 13 consecutive patients with histologically proven IgG4-ROD and a control group of 29 consecutive OAL-patients diagnosed between 10/2014 and 09/2019. Statistical significance was accepted at a p<0.05 significance level. RESULTS: IgG4-ROD-patients had longer time-to-diagnosis, higher orbital recurrence rates, but smaller lesions compared to OAL-patients (p=0.002; p=0.006 and p=0.006; Mann-Whitney U-test). Frequent cross-sectional imaging findings in both IgG4-ROD-patients and OAL-patients included extraocular muscle enlargement (92% and 93%, respectively; most often in the lateral rectus muscles and the levator-complex), and lacrimal-gland enlargement (85% and 83%, respectively). Other imaging findings comprised infraorbital nerve-involvement (IgG4-ROD, 23%, OAL, 17%) and orbital fat inflammation (IgG4-ROD, 23%, OAL, 28%). Bony infiltration and remodeling, heterogenous contrast-media distribution, and infiltration of the lacrimal system were seen slightly more often in IgG4-ROD (23%, 38%, 15% and 15% versus 17%, 14%, 3% and 7%). However, cross-sectional imaging features did not differ significantly between patient subgroups. Clinical symptoms predominantly occurred unilaterally (IgG4-ROD, 9/13, 69%, OAL, 24/29, 83%), while imaging findings were most often bilateral (IgG4-ROD, 11/13, 85%, OAL, 23/29, 79%, p<0.001, McNemar test). CONCLUSION: No morphological cross-sectional imaging sign could reliably distinguish between IgG4-ROD and OAL, leaving histopathology indispensable for definite diagnosis. Yet, importantly, for both IgG4-ROD and OAL, cross-sectional imaging frequently detected bilateral orbital disease when only one eye was clinically affected.

Subclinical dysthyroid optic neuropathy: tritan deficiency as an early sign of dysthyroid optic neuropathy.

PURPOSE: The aim of this research was to investigate the subclinical findings of dysthyroid optic neuropathy (DON) and to look for early indicators for optic nerve compression in patients with Graves' orbitopathy. PATIENTS AND METHODS: In this observational, retrospective study, the medical charts of 24 patients (32 eyes) with a diagnosis of DON between 2008 and 2019 were included. Our goal was to identify potential pathological signs in patients with DON prior to the definitive diagnosis of DON. RESULTS: We discovered that the earliest pathological sign in the subclinical cases was tritan deficiency obtained with a standardised colour vision test by Arden. In all cases but one, regardless of the visual field (VF) defects, the tritan values were pathological (based on a threshold of ≥8%) in the subclinical phase. The mean tritan value was 19.12% (range 6.9-80.8%) at the time of the subclinical phase and 32.16% (range 6.3-100.0%) at the time of the diagnosis of DON. The sensitivity of the colour vision test was 20% for protan and 96.67% for tritan in the subclinical phase. At the time of the definitive diagnosis of DON, the sensitivity of protan was 48.15% compared to 96.30% for tritan. CONCLUSION: We found that changes in vision affecting the blue-yellow (tritan) colours resulting from the compression of optic nerve, even in affected patients with normal VF tests, are a reliable early sign of DON.

Screening for Predictive Parameters Requiring Psycho-Oncological Intervention via the National Comprehensive Cancer Network Distress Thermometer in the Follow-Up of Uveal Melanoma Patients.

AIM: To assess a profile of uveal melanoma patients at risk of requiring active psycho-oncological intervention by employing the National Comprehensive Cancer Network (NCCN) distress thermometer. METHODS: Multivariate correlation and multiple linear regression analysis of data collected retrospectively from 106 consecutive patients suffering from uveal melanoma. RESULTS: Distress levels correlated with practical (p = 0.01), emotional (p = 0.003) and physical problems (p = 0.001) as well as the total number of issues reported (p < 0.001; ANOVA, respectively). Emotional issues added up to 39% of influence on distress levels. Nervousness, worry and sadness as the most important emotional issues tested correlated significantly with anatomic stage, tumor T-category, metastatic status and time after primary diagnosis and were present more frequently in patients with higher distress levels (p < 0.001, p = 0.002, p = 0.004, respectively, Fisher's exact test). Pre-existing psycho-oncological support was more frequent in metastatic patients and patients with higher anatomic stage tumors (p = 0.008 and p = 0.003; Fisher's exact test). CONCLUSION: The distress thermometer proved to be useful for rapid assessment of patients requiring active intervention. A higher number of distress items recorded correlated with elevated distress levels. Emotional issues were responsible for the majority of problems. A typical patient profile at risk of developing distress requiring close attention of caregivers includes high anatomic stage, high T-category, presence of metastases and early follow-up. Correct diagnosis and interpretation of distress-levels should help improve the quality of life of uveal melanoma survivors. TRIAL REGISTRATION: Not applicable.

Evaluation of medical and surgical decompression in patients with dysthyroid optic neuropathy.

PURPOSE: To evaluate the effectiveness of steroid-pulse therapy and three-wall orbital decompression in patients with dysthyroid optic neuropathy (DON). METHODS: Twenty-five patients (46 eyes) with a diagnosis of DON between 2008 and 2015 were included in the study. The first group (7 patients, 16 eyes) consisted of patients with a steroid-pulse treatment only and the second group (18 patients, 30 eyes) included patients with medical and surgical decompression. RESULTS: Twenty patients were female; five patients were male. After the diagnosis of DON, all patients were treated with steroid-pulse treatment (intravenous 500 mg prednisolon twice/week for 4 weeks, 250 mg twice/week for 2 weeks) as a first-line treatment (medical decompression). In 30 eyes (18 patients) out of 46 eyes, (25 patients) an orbital decompression was needed to preserve the optic nerve function. In those therapy-resistant cases (surgical decompression group), the orbital decompression led to statistically significant improvements in best-corrected visual acuity (BCVA), protan and tritan value of the color vision (p = 0.007, p < 0.0001, p = 0.019, respectively, comparison of first visit to last visit). CONCLUSION: According to our data, the mild cases of DON with better initial visual acuity (in our case series mean: 0.3 logMAR) seem to respond well to steroid treatment. However, therapy-resistant cases with an impaired initial BCVA (in our case series, mean: 0.6 logMAR) seem to need the surgery to preserve the optic nerve function. In conclusion, this retrospective study confirms the effectiveness of surgical decompression in therapy-resistant cases of DON.

The national comprehensive cancer network distress thermometer as a screening tool for the evaluation of quality of life in uveal melanoma patients.

PURPOSE: To assess quality of life (QoL) status via the National Comprehensive Cancer Network (NCCN) distress thermometer as a psychooncological screening tool in uveal melanoma patients. METHODS: One hundred and six consecutive patients suffering from uveal melanoma completed the distress thermometer between 04/2018 and 12/2018. Practical, emotional, family concerned, spiritual, physical and overall distress levels, distribution of distress and subgroup analyses defining groups of potential high distress levels in need of intervention were assessed. Descriptive statistics, cross-tabulations, chi-square and Fisher's exact test as well as correlation coefficients (Spearman's rho) and receiver operating characteristic (ROC) were used for analysis. RESULTS: Patients with higher T-category had significantly more emotional problems and spiritual concerns (p = 0.046 and p = 0.023, respectively). Female patients accounted for higher rates of physical issues (p = 0.034). Lower best corrected visual acuity (BCVA) was correlated with higher distress levels (p = 0.037). Patients resulting in loss of BCVA of ≥3 lines reported higher distress levels (p = 0.029). A distress threshold of 5 on the basis of ROC analysis showed a corresponding sensitivity of 100% and specificity of 76%. CONCLUSION: The NCCN distress thermometer could be integrated well into our clinical routine and proved to be a rapid, yet sensible screening tool for emotional and physical distress in patients with uveal melanoma. Special attention should be paid to patients with higher T-category and patients resulting in lower levels of BCVA. As in patients with different tumour entities, the established distress threshold of ≥5 proposing intervention proved to be adequate for uveal melanoma patients.

Combined positron emission tomography/computed tomography for diagnosis and monitoring of orbital adnexal lymphoma.

PURPOSE: Combined whole-body F-18-fluoro-2-deoxyglucose positron emission tomography / computed tomography ([18F]FDG-PET/CT) gives precise information about tumour morphology and metabolism. The standardized uptake value (SUV) allows quantification of tumour metabolism. The diagnostic value of PET/CT in patients with suspected orbital adnexal lymphoma (OAL) was evaluated. METHODS: Of 21 patients with suspected OAL who underwent combined whole-body PET/CT between 07/2002 and 11/2016, 16 were scanned before and five after orbital biopsy. Histological tumour determination was performed in all cases via biopsy. Correlation between SUVmax and therapeutic status, lymphoma stage (Ann Arbor classification) and histological grading was tested. RESULTS: All lesions could be depicted by combined whole-body PET/CT. Histology confirmed two malignant T-cell and 18 malignant B cell non-Hodgkin lymphomas as well as one patient suffering from systemic lymphoma with chronic polypoid sinusitis. SUVmax levels of orbital findings were significantly lower after therapy (p < 0.001; Fisher's exact test). Higher stage lymphomas (Ann Arbor classification) expressed significantly higher SUVmax levels (p = 0.014; Fisher's exact test). There was no significant correlation of SUVmax values and histologic grading in this patient collective. CONCLUSION: Positron emission tomography/computed tomography (PET/CT) depicted vital tumour metabolism of OALs accurately. In cases scanned after orbital biopsy and under systemic therapy, no elevated tumour metabolic activity was expressed. This underlines the reasonable application of PET/CT for therapy monitoring besides whole-body staging. Higher-stage OALs show higher metabolic activity. Yet, for adequate therapy initiation, histology remains indispensable.

Combined positron emission tomography/computed tomography (PET/CT) for imaging of orbital tumours and tumours extending into the orbit.

OBJECTIVE: To assess clinical and radiological performance of combined positron emission tomography/computed tomography (PET/CT) in patients with secondary and primary intraorbital tumours. METHODS: 14 adults with secondary and 1 child with primary orbital masses underwent combined whole-body PET/CT. Radiopharmaceutical tracers applied were (18F)-fluorodeoxyglucose, (18F)-fluoroethylcholine (FEC) and (68Ga)-DOTATATE. Histopathology and/or all conventional radiographic work-up and clinical course served as standard of reference. Descriptive statistics and Fisher's exact test were used for analysis. RESULTS: PET/CT detected all orbital masses. All 15 patients had malignant disease. Local osseous infiltration was correctly identified in 11 patients. Lymph node metastases were present in two of eight patients (25%) with haematogenous orbital metastases and in five of six patients (83%) with infiltrative carcinoma (p=0.05). Further distant metastases were present in all eight patients suffering from orbital metastases, but only one patient with infiltrative carcinoma (17%) presented with disseminated disease (p=0.003). In one metastasis, PET/CT excluded vital orbital tumour tissue after radiation therapy. Local recurrence was detected in another patient suffering from prostate cancer. CONCLUSION: PET/CT is a sensitive tool for the detection and localisation of orbital masses, enabling assessment of both morphology and cell metabolism. Detailed imaging of the head and neck region with a small field-of-view should be performed when suspecting lymphatic metastases. As metastatic disease to the orbit is associated with advanced disease, focus should be laid on whole-body imaging for staging of these patients. Different radiopharmaceutical tracers can be applied to distinguish the origin of orbital metastases.