Abstract Traditionally, the mainstay of treatment for advanced keratoconus (KC) has been either penetrating or deep anterior lamellar keratoplasty (PK or DALK, respectively). The success of both ...operations, however, has been somewhat tempered by potential difficulties and complications, both intraoperatively and postoperatively. These include suture and wound-healing problems, progression of disease in the recipient rim, allograft reaction, and persistent irregular astigmatism. Taken together, these have been the inspiration for an ongoing search for less troublesome therapeutic alternatives. These include ultraviolet crosslinking and intracorneal ring segments, both of which were originally constrained in their indication exclusively to eyes with mild to moderate disease. More recently, Bowman layer transplantation has been introduced for reversing corneal ectasia in eyes with advanced KC, re-enabling comfortable contact lens wear and permitting PK and DALK to be postponed or avoided entirely. We offer a summary of the current and emerging treatment options for advanced KC, aiming to provide the corneal specialist useful information in selecting the optimal therapy for individual patients.
The purpose of this study was to describe the incidence of graft detachment after Descemet membrane endothelial keratoplasty (DMEK) without postoperative supine posturing.
A total of 106 eyes of 84 ...patients with Fuchs endothelial corneal dystrophy or bullous keratopathy (BK) were operated by a single experienced surgeon with DMEK with a 99% anterior chamber air bubble fill, recovered in an upright (seated) position, and then discharged without instructions to remain supine. Postoperatively, all eyes were evaluated for graft detachment through anterior segment optical coherence tomography at predetermined intervals (1 d, 1 wk, and 1 mo). Detachments were regarded as clinically significant if they subtended 30% of the total graft surface area or involved the visual axis.
Clinically significant graft detachments were observed in 23 of 106 eyes (22%) in the no-supine posturing cohort, including 22 of 85 eyes (26%) operated for Fuchs endothelial corneal dystrophy and 1 of 21 eyes (5%) operated for BK. Compared with a historical comparison group of eyes undergoing DMEK with 48 hours of postoperative supine posturing, the risk of graft detachment was not increased. In both cohorts, 6% of operated eyes required regrafting for either persistent detachment or primary graft failure. No additional intraoperative or postoperative complications were experienced.
Particularly in eyes operated for BK, the supine posturing requirement after DMEK may be eliminated without increasing the absolute risk for clinically significant graft detachment.
Topoisomerases are expressed throughout the developing and adult brain and are mutated in some individuals with autism spectrum disorder (ASD). However, how topoisomerases are mechanistically ...connected to ASD is unknown. Here we find that topotecan, a topoisomerase 1 (TOP1) inhibitor, dose-dependently reduces the expression of extremely long genes in mouse and human neurons, including nearly all genes that are longer than 200 kilobases. Expression of long genes is also reduced after knockdown of Top1 or Top2b in neurons, highlighting that both enzymes are required for full expression of long genes. By mapping RNA polymerase II density genome-wide in neurons, we found that this length-dependent effect on gene expression was due to impaired transcription elongation. Interestingly, many high-confidence ASD candidate genes are exceptionally long and were reduced in expression after TOP1 inhibition. Our findings suggest that chemicals and genetic mutations that impair topoisomerases could commonly contribute to ASD and other neurodevelopmental disorders.
Corneal allogenic intrastromal ring segments (CAIRS) are semicircular pieces of donor corneal stroma, which may be surgically implanted to flatten keratoconic corneas. These segments can be trimmed ...to different thicknesses; whereas thicker segments confer greater flattening, their bulk renders them more technically challenging to insert. Consequently, thinner segments are often preferred, especially for starting surgeons. Here, we describe a technique for transiently thinning CAIRS to facilitate easy insertion, thereby permitting the use of thicker segments to achieve the maximal flattening effect.
To describe discrepancies between clinical observation and current teachings in corneal endothelial disease, particularly in Fuchs endothelial dystrophy and its potential association with primary ...open angle glaucoma.
Perspective.
A perspective is presented on Fuchs dystrophy, a disorder that commonly presents with a compromised endothelium but minimal stromal edema, indicating that the corneal imbibition pressure is relatively “too high.”
The discrepancy between the relative lack of stromal edema in the absence of an endothelial cell layer cannot be explained by the current theories involving a circulatory pumping mechanism over the endothelial cell layer, but may point to the following: (1) secondary involvement of the corneal endothelium in Fuchs dystrophy; (2) separate hydration systems for maintaining the imbibition pressure (vertical static hydration) and corneal nutrition (horizontal dynamic hydration); (3) the cornea as net contributor of aqueous humor; (4) a close relationship between the corneal imbibition and intraocular pressure, with potentially a shared regulatory system; and (5) a potential steroid-type hormone dependency of this regulatory system.
Clinical observation shows that the stromal imbibition pressure is “too high” in Fuchs endothelial dystrophy, indicating that it may not primarily be an endothelial disease, but a type of “corneal glaucoma.”
Corneal allogenic ring segments (CAIRS) are semicircular pieces of donor corneal stroma which may be surgically implanted to flatten keratoconic corneas. Conventionally, these donor segments are ...inserted into channels created via femtosecond laser dissection. However, access to femtosecond technology is not universal. Here we describe an alternate, manual technique for channel creation which is femtosecond laser independent.