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.

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.