Slow Interstitial Fluid Flow Activates TGF-ß Signaling and Drives Fibrotic Responses in Human Tenon Fibroblasts.

BACKGROUND: Fibrosis limits the success of filtering glaucoma surgery. We employed 2D and 3D in vitro models to assess the effects of fluid flow on human tenon fibroblasts (HTF). METHODS: HTF were exposed to continuous or pulsatile fluid flow for 48 or 72 h, at rates expected at the transscleral outflow site after filtering surgery. In the 2D model, the F-actin cytoskeleton and fibronectin 1 (FN1) were visualized by confocal immunofluorescence microscopy. In the 3D model, mRNA and whole cell lysates were extracted to analyze the expression of fibrosis-associated genes by qPCR and Western blot. The effects of a small-molecule inhibitor of the TGF-ß receptor ALK5 were studied. RESULTS: Slow, continuous fluid flow induced fibrotic responses in the 2D and 3D models. It elicited changes in cell shape, the F-actin cytoskeleton, the deposition of FN1 and activated the intracellular TGF-ß signaling pathway to induce expression of fibrosis-related genes, such as CTGF, FN1 and COL1A1. ALK5-inhibition reduced this effect. Intermittent fluid flow also induced fibrotic changes, which decreased with increasing pause duration. CONCLUSIONS: Slow interstitial fluid flow is sufficient to induce fibrosis, could underlie the intractable nature of fibrosis following filtering glaucoma surgery and might be a target for antifibrotic therapy.

Longitudinal Analysis of the ASES and Constant-Murley Scores, and the Internal Rotation/Shift and Jobe Tests Following Arthroscopic Repair of Supraspinatus Lesions.

It is essential to investigate patients post-surgery using functional surveys like the American Shoulder and Elbow Surgeons Shoulder (ASES) and the Constant-Murley shoulder (CMS) scores, as well as clinical tests, such as the Internal Rotation and Shift (IRO/Shift) and Jobe tests. In this study, 51 out of an initial 87 patients underwent an arthroscopic supraspinatus repair (22 single-row, 16 double-row, 13 debridement). Testing occurred pre-surgery, and 3 and 6 months post-surgery. Both surveys showed significant improvements over time among all 87 patients, but there were no differences between groups (lesion/no lesion) (p > 0.815) or time × group (p > 0.895). The IRO/Shift test showed a stronger ability to distinguish between both groups (positive vs. negative) with respect to the ASES and CMS scores over time, but the Jobe test did not (p > 0.100). Improvements in the CMS scores and the Jobe test were lower following repair compared to the ASES and IRO/Shift test. Most patients returned to adequate levels of functional abilities at 6 months post-surgery. The time required to return to activities of daily living and negative clinical tests was longer for the double-row repair patients compared to the single-row and debridement groups. In conclusion, both the functional surveys and the clinical tests demonstrated improvements following surgery.

Indications, techniques, and graft survival of mini and corneo-scleral tectonic keratoplasties: A retrospective single-center case series.

PURPOSE: Tectonic keratoplasties (TK) are used to treat corneal and scleral perforations and to prevent the loss of the eye. In this study, we retrospectively analyzed indications, surgical procedures, and outcomes of eccentric mini and corneo-scleral tectonic keratoplasties with respect to anatomical survival and clear graft survival rates to identify risk factors for graft failure. METHODS: This retrospective study includes 33 eccentric mini (graft diameter <6 mm) and/or corneo-scleral TK of 32 consecutive patients of a total of 41 TK carried out between 2005 and 2020 in the Eye Center, University of Freiburg, Germany, making up 0.7% of all keratoplasties performed during this period (n = 5557). Patient and graft specific data were extracted from medical files. Anatomical survival-defined as achieving integrity of the globe without further surgical interventions-and clear graft survival-defined as persisting graft clarity-were estimated using the Kaplan-Meier method. We also fitted Cox proportional hazard models to account for factors influencing anatomical and clear graft survival. RESULTS: Median duration of anatomical success was 72.5 months (95% confidence interval (CI) 18.1-infinite (inf.)) and median duration of clear graft survival was 29.6 months (95% CI 12.5-Inf.). The 1-year survival rate for anatomical survival was 67.6% (95% CI 52.2% - 87.6%) and for clear graft survival 66.4% (95% CI 50.5%- 87.1%). No enucleation was necessary during this time-period. Non-inflammatory primary causes (n = 14) presented a trend towards better anatomical survival rates (median remained above 0.75 during follow-up) compared to inflammatory primary causes (n = 19, median 18.1 months (95% CI 2.8 - inf.)) and longer clear graft survival (median 29.6 months (95% CI 12.5 - inf.) versus 13.1 months (95% CI 3.2 - inf.)). Corneo-scleral grafts (n = 18) compared to corneal grafts (n = 15) showed a trend towards better anatomical survival (more than 50% of eyes did not fail during follow-up period (95% CI 21.9-Inf. months) versus 18.1 months (95% CI 2.4-Inf.)) and clear graft survival (median 29.6 months (95% CI 12.6-Inf.) versus 6.2 months (95% CI 2.8-Inf.)). Old age (n = 11, 75.2 - 90.1 years) compared to young age (n = 11, 6.2 - 60.2 years) was the only hazard ratio (hazard ratio 0.04 (95% CI 0.002-0.8)) that reached the level of significance (p = 0.03). CONCLUSION: Eccentric TK is helpful in the successful treatment of a variety of severe eye diseases. Patients at young age, with pre-existing inflammatory conditions or corneal TK are at higher risk for anatomical failure as well as clear graft failure and therefore need to be monitored closely.

Caruncle dysgeneses - A case series.

Purpose: Caruncle dysgeneses are extremely rare and must be differentiated from caruncular and conjunctival tumors. Very few case reports with histopathological descriptions exist. In this case series, four patients with five caruncle dysgeneses, two with histopathological findings, are characterised. Observations: Patient 1, a 26-year-old woman, presented with a conjunctival change at the left lower eyelid she had first noticed seven months earlier. She reported foreign body sensation and itching. On her left eye was a subtarsal conjunctival tumour measuring approximately 4 × 4 mm with whitish sebaceous gland-like inclusions located almost in the fornix morphologically resembling the nearby caruncle. The patient was asymptomatic after excision. Histopathological examination of the excised tissue showed non-keratinizing squamous epithelium with goblet cells. Subepithelially, there was lymphoplasmacytic cellular infiltration with intervening epidermal cysts adjacent to sebaceous glands and underlying adipose tissue, but no hair follicles or sweat/lacrimal glands. The epidermal cysts contained scattered hairs. A diagnosis of supernumerary caruncle was made.Patient 2, a 56-year-old woman, was referred for evaluation of a caruncle tumour that was reported to be present since childhood. Clinically the 5 × 5 mm measuring tumour appeared yellowish and less reflective compared to the normal caruncle tissue. Histopathologically, non-keratinizing squamous epithelium with goblet cells was found. In the area of more exposed tumour tissue, there were significantly fewer goblet cells and incipient keratinization of the superficial epithelial layers. Subepithelially, sebaceous glands and adipocytes were present. Hair follicles or sweat/lacrimal glands were not evident. A diagnosis of megacaruncle was made.Patient 3, a 58-year-old woman with Goldenhar syndrome, was clinically diagnosed with a supernumerary caruncle on the right eye as an incidental finding.Patient 4, a 24-year old man, clinically presented with a megacaruncle on the right eye and a supernumerary caruncle on the left. Conclusions: Caruncle dysgeneses are often asymptomatic and have to be differentiated from other caruncular and conjunctival tumors. If they are present, attention should be paid to signs of an oculo-auriculo-vertebral spectrum as Goldenhar syndrome. In case of unclear findings or complaints, excision with subsequent histopathological examination is required.

[Corneal endothelial cell photography: comparison of smartphones]. / Korneale Endothelzellfotografie: Vergleich von Smartphones.

BACKGROUND: The documentation of ophthalmologic findings using smartphone photography can confirm diagnoses and enable follow-up assessments in outpatient care. Photographing corneal endothelial cells using a smartphone on a slit lamp is complex for both smartphone and examiner. Smartphone models differ in their ability to quickly and safely take images of the corneal endothelium. AIM OF THIS WORK: In this paper different smartphone models are presented with respect to their applicability for corneal endothelial cell photography and success factors for good smartphone imaging are described. MATERIAL AND METHODS: In a cross-sectional study, a selection of 16 different smartphone models were compared with respect to their use in corneal endothelial cell photography. The smartphones were attached to the slit lamp eyepiece using an adjustable adapter. It was tested whether high-quality endothelial cell images of healthy subjects could be obtained within 3 min using the standard photo app of the respective smartphone. In addition, the subjective difficulty of creating the image was recorded. Factors contributing to successful imaging of corneal endothelial cells were summarized in a figure. RESULTS AND DISCUSSION: Distinct differences regarding feasibility and quality of endothelial cell photography were detected between the different smartphones. Not every smartphone is suitable for endothelial cell photography.

A Longitudinal Analysis of the Internal Rotation and Shift (IRO/Shift) Test Following Arthroscopic Repair of Superior Rotator Cuff Lesions.

Although the use of clinical tests to diagnose superior rotator cuff pathology is common, there is paucity in the research regarding the accuracy of such tests following arthroscopic repair. The aim of this study was to determine the accuracy of the IRO/Shift test compared to the Jobe test at 3 months and 6 months post-surgery for superior rotator cuff repair. Arthroscopic repair was conducted on 51 patients who were subsequently seen for clinical evaluation at 3 and 6 months following surgery. At 3 months post-surgery only 27% of the patients had a negative IRO/Shift test and 18% had a negative Jobe test. However, at 6 months 88% of the patients presented with a negative IRO/Shift test and 61% a negative Jobe test. When compared to each other, the IRO/Shift test and the Jobe test had 90% agreement pre-operatively, 71% agreement at 3 months post-surgery, and 67% agreement at 6 months. These results demonstrate that the accuracy of the IRO/Shift test and the Jobe test improved between 3 and 6 months following arthroscopic surgery of the superior rotator cuff, with the IRO/Shift test having better accuracy.

IRO/Shift Test Is Comparable to the Jobe Test for Detection of Supraspinatus Lesions.

To determine how the internal rotation and shift (IRO/shift) test compares to the gold standard of clinical tests (Jobe test) for diagnosing supraspinatus lesions and to confirm these clinical results with surgical findings, 100 symptomatic patients were clinically examined between October 2018 and November 2019. All 100 patients were evaluated using both the IRO/shift test and Jobe test. A total of 48 of these patients received surgical intervention. Based on these data, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for both the IRO/shift test and Jobe test were calculated. The IRO/shift test had a sensitivity of 96% (95% CI: 82-100%), specificity of 50% (95% CI: 27-73%), PPV of 73% (95% CI: 56-86%), NPV of 91% (95% CI: 59-100%), and an accuracy of 77% (95% CI: 63-88%). The Jobe test had a sensitivity of 89% (95% CI: 72-98%), specificity of 60% (95% CI: 36-81%), PPV of 76% (95% CI: 58-89%), NPV of 80% (95% CI: 52-96%), and an accuracy of 77% (95% CI: 54-81%). These results suggest that the IRO/shift test is comparable to the Jobe test, which is often viewed as the gold standard clinical examination for assessing supraspinatus lesions. This study was approved by the Ethics Commission of the Martin Luther University Halle-Wittenberg (reference number: 2018-05).

The internal rotation and shift-test for the detection of superior lesions of the rotator cuff: reliability and clinical performance.

Background: Using reliable and valid clinical tests are essential for proper diagnosis and clinical outcomes among injuries involving the rotator cuff. The addition of a new clinical examination test could improve the clinical diagnosis and informative value of the sensitivity and specificity of pathology. This study of diagnostic accuracy evaluated the use of a new rotator cuff test, called the internal rotation and shift-test (IRO/shift-test), to determine its reliability and clinical performance (sensitivity, specificity, positive (PPV)/negative predictive value (NPV)). Clinical diagnostic outcomes were confirmed with radiological findings (MRI). Methods: 100 patients from a specialized shoulder unit participated (64 male, 36 female, mean age: 55 ± 13.5 years). A single-blinded (no knowledge of prior clinical or technical diagnostics) study design was used with two experienced physicians performing the IRO/shift-test. For clinical performance, all clinical testing was compared with MRI. Results: The intra-rater (ICC = 0.73, 95% CI: 60-82) and inter-rater (ICC = 0.89, 95% CI: 81-94) coefficients for the IRO/shift-test showed good-to-excellent reliability. 75% of the patients showed a positive IRO/shift-test, while 65% had a radiologically diagnosed superior rotator cuff tear. 60% of these patients had both a positive IRO/shift-test and objective rotator cuff tear via MRI. The sensitivity of the IRO/shift-test to detect superior rotator cuff lesions based on MRI diagnosis was calculated at 92% (95% CI: 86-99%), while specificity was 67% (95% CI: 50-84%). Predictive values were also found to be high with 86% PPV (95% CI: 78-94%) and 80% NPV (95% CI: 64-96%). Conclusion: Our results demonstrate that the IRO/shift-test is a reliable and valid tool for assessing superior rotator cuff pathology. With good-to-excellent intrarater and inter-rater reliability and strong sensitivity and specificity this test should be considered a valuable addition to clinicians' cadre of clinical evaluation tools.