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.
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.
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.”
To describe two cases of suprachoroidal hemorrhage during Descemet membrane endothelial keratoplasty (DMEK).
Two patients with pseudophakic bullous keratopathy (PBK) underwent DMEK and proceeded to ...develop intraoperative suprachoroidal hemorrhage. Reports of both cases are documented, including potential risk factors, intraoperative events, and postoperative outcomes and interventions.
Both cases required premature abortion of the operation following the abrupt onset of significant posterior pressure indicating potential suprachoroidal hemorrhage. Postoperative visual acuity measured light perception or worse, and both patients declined further intervention.
Suprachoroidal hemorrhage is a rare but potentially devastating intraoperative complication which may occur during DMEK, particularly in eyes with relevant risk factors. An inability to deepen the anterior chamber following graft implantation may signify the condition.
To evaluate the feasibility and clinical outcomes of Descemet membrane endothelial keratoplasty (DMEK) in eyes with a glaucoma drainage device (GDD).
Retrospective, interventional case series.
...Clinical outcomes of 23 DMEK procedures for bullous keratopathy (52%), failed previous transplant (39%), or Fuchs endothelial corneal dystrophy (9%) in 20 eyes (19 patients) with a GDD were retrospectively analyzed at 2 tertiary referral centers. Main outcome measures were best-corrected visual acuity (BCVA), endothelial cell density (ECD), postoperative complications, and graft survival.
Mean length of postoperative follow-up after DMEK was 19 (±17) months. Kaplan-Meier survival analysis showed an 89% cumulative graft success rate at 1 year postoperatively. At 1 year postoperatively (n = 15 eyes), BCVA improved by ≥2 Snellen lines in 11 eyes (73%) and remained stable in 4 eyes (27%). Donor ECD decreased by 37% (n = 14), 60% (n = 11), and 71% (n = 11) at 1, 6, and 12 months postoperatively, respectively. Postoperative complications up to 2 years postoperatively comprised pupillary block in 1 eye (successfully reversed by partial air removal), visually significant graft detachment requiring rebubbling in 5 eyes (22%), allograft rejection successfully reversed with topical steroids in 2 eyes (9%), secondary graft failure in 2 eyes (9%), and cataract in 1 of 3 phakic eyes (33%). Re-keratoplasty was required in 2 eyes (9%).
With specific surgical modifications, DMEK provided acceptable clinical outcomes when taking the complexity of these eyes into account. However, presence of a GDD may reduce graft survival times and may pose a risk for more frequent regrafting.
Purpose
To compare the clinical outcomes of intracorneal ring segment (ICRS) implantation in eyes with advanced vs. mild/moderate keratoconus (KCN).
Methods
A retrospective analysis of 141 eyes of ...111 patients with KCN who underwent ICRS implantation. Preoperative maximum keratometry (Kmax) was <57 diopters (D) in 70 eyes and >57 D in 71 eyes. Postoperatively, corrected distance visual acuity (CDVA), Kmax, and intraoperative and postoperative complications were assessed at 1 day, 1 month, and 1 year.
Results
Corneas with a preoperative Kmax >57 D experienced greater reduction in axial curvature after ICRS implantation than corneas with a preoperative Kmax <57 D (7.0 D vs. 5.5 D, p=0.005) and gained more Snellen lines of CDVA (3 vs. 1, p<0.001) by 1 year postoperatively. The incidences of the most prevalent complications (explantation, extrusion, and infectious keratitis) did not differ significantly between the two groups (p=0.29, p=0.99, p=0.98).
Conclusions
The visual and topographic effects of ICRS implantation are greater in eyes with more advanced KCN, with no increase in the incidence of the most common complications.
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