No abstract

Background This study aimed to analyze if the outcome after corneal crosslinking (CXL) in progressive keratoconus patients depends on the stage at which the procedure is performed. This knowledge would help to improve success of CXL and to define surgery indications in those patients. Methods In this retrospective study, 124 consecutive eyes of 100 patients with progressive keratoconus undergoing corneal CXL at the University Eye Hospital Tübingen were included. The eyes were graded according to modified Krumeich stages depending on induced myopia or astigmatism, corneal radii, minimum corneal thickness, and morphological changes. The observation period covered November 2008 to September 2018. Preoperatively, 12 and 24 months after CXL, the best corrected visual acuity (BCVA) was determined and astigmatism as well as tomographic parameters (Kmax, Kmin, central corneal thickness (CCT), minimum corneal thickness (MCT)) were measured by means of a Scheimpflug camera system. Results BCVA results showed significant differences between the modified Krumeich stages at 12 months (p = 0.014) and at 24 months postoperatively (p = 0.032). Also, astigmatism differed significantly among the stages at 24 months after CXL (p = 0.023). However, no significant differences regarding astigmatism were detectable after 12 months. In terms of Kmax, Kmin, CCT, and MCT, no significant differences between the Krumeich stages were observed. Conclusions BCVA showed a significantly higher improvement after CXL in the early stage of keratoconus compared to a higher stage. However, the postinterventional tomographic values did not differ significantly between the different modified Krumeich stages. The significantly higher improvement in BCVA after CXL in the early stage might indicate that earlier intervention provides a higher subjective benefit to the individual. Further studies with larger sample sizes are needed to confirm these findings.

ABSTRACT.Purpose: Glaucoma filtration surgery (GFS) fails due to fibrosis. The a5b1-integrin plays a pivotal role in fibrosis, angiogenesis and inflammation. This is the first experiment evaluating the prevention of fibrosis after GFS by a specific small molecule a5b1-integrin inhibitor (CLT-28643). Methods: Twenty-four rabbits received trabeculectomy on their right eyes. The rabbits were randomized into three groups of eight eyes each. CLT-28643 was given as a single subconjunctival injection intraoperatively to two of the right eye groups followed by postoperative vehicle eye drops (CLT+ group) or CLT-28643 eye drops 4 times daily (CLT++ group). A third group received mitomycin-C (MMC) intraoperatively (sponge application, 0.04%, 2 min) followed by vehicle eye drops postoperatively. The control-surgery group consisted of 12 left eyes having trabeculectomy with no adjunctive therapy. The remaining 12 left eyes formed the untreated group. Clinical assessment included intraocular pressure (IOP) measurement, slit-lamp examination (including bleb survival and morphology) and bleb photography. The rabbits were killed after four weeks for histology. Results: Both CLT-28643-treated groups showed significantly prolonged bleb survival, and better bleb score compared to the control-surgery group. At end of the study, most functioning blebs were found in the MMC group (MMC group 75%; CLT+ group 12.5%, CLT++ group 25%; CLT+ group 12.5%, controlsurgery group 0%). CLT-28643 was non-toxic and well tolerated. Conclusions: This rabbit GFS study indicates that inhibition of a5b1-integrin by the novel a5b1-integrin antagonist CLT-28643 significantly improved the outcome. The effect of a single intro-operative application of CLT-28643 seems to be inferior to 0.04% MMC.

This chapter argues for compositionalism, which is the view that a fictional text can consist of both fictional and factual discourse. One reason to think compositionalism is true is that it explains why authors go to great lengths, and commit to high levels of superfluous detail, to achieve accuracy in their works. This chapter argues for compositionalism within a framework of an institution of fictionality. The conventions of this institution are detailed and provide the basis on which we can identify factual discourse in an overall fictional context: Specific signposts of factuality demand of the reader that he read the utterance as factual and consider it to be a source of knowledge. Therefore, compositionalism allows for reliable beliefs to be formed on the basis of engaging with fictions.