Crosslinking-Induced Corneal Endothelium Dysfunction and Its Protection by Topical Ripasudil Treatment

Purpose. To investigate the changes of corneal endothelium under different crosslinking conditions and the protective effect of ripasudil. Methods. Corneal crosslinking groups were infiltrated with riboflavin and subsequently irradiated with 0.54 J/cm2 or 1.08 J/cm2 UVA, while noncrosslinking groups included neither UVA nor riboflavin treatment, only 1.08 J/cm2 UVA and only riboflavin treatment. Corneal opacity, variations in corneal endothelial cells, and corneal thickness of all groups were observed by slit lamp, in vivo confocal microscopy, and optical coherence tomography. Immunofluorescence staining and scanning electron microscopy were performed to evaluate changes in the structure and function of the corneal endothelium. The mice that received a corneal crosslinking dose of 1.08 J/cm2 were instilled with ripasudil to explore its protective effect on the corneal endothelium. Results. Treatment with UVA and riboflavin caused an increase in corneal opacity and corneal thickness and decreased endothelial cell density. Furthermore, treatment with UVA and riboflavin caused endothelial cell DNA damage and destroyed the tight junction and pump function of the endothelium, while riboflavin or the same dose of UVA alone did not affect the endothelium. Ripasudil reduced DNA damage in endothelial cells, increased the density of cells, and protected the endothelium’s integrity and function. Conclusion. Riboflavin combined with UVA can damage the corneal endothelium’s normal functioning. The corneal endothelium’s wound healing is dose-dependent, and the ROCK inhibitor ripasudil maintains the endothelium’s pump and barrier functions.

The influence of corneal density and thickness on tonometry measurement with goldmann applanation, non-contact and iCare tonometry methods

Purpose To evaluate the effect of corneal density and thickness on the accuracy of tonometry readings obtained via three most used techniques. Method Intraocular pressures of 45 patients’ right eyes were measured using Goldmann Applanation, iCare, and non-contact tonometry methods. Corneal parameters were obtained using the Pentacam Camera System. Data obtained were analyzed using Paired t Test, Pearson’s correlation coefficient, multiple linear regression analysis, and Bland–Altman plots. Results The mean corneal thickness was 545.4 ± 3.93 μm. The mean corneal density of total, stromal, 0–2 mm, and 2–6 mm zones were 27.85 ± 6.23 GSU, 24.61 ± 6.05 GSU, 20.76 ± 2.96 GSU, and 20.81 ± 3.51 GSU respectively. IOP readings had a statistically significant correlation with corneal stromal thickness, as well as with total and stromal density. The stromal density, however, showed higher correlation with the three tonometry methods than did the total density (iCare: − .482 (0.001) stromal density versus− .464 (0.001) total density, NCT: − .376 (0.011) versus − .353 (0.017), GAT: − .306 (0.041) versus − .296 (0.048)). Statistical differences were found in comparing the iCare readings with GAT (P < 0,00) and with NCT (P < 0,00), with mean differences of 1.8 mmHg ± 2.6 and 2.0 mmHg ± 2.6 respectively. GAT and NCT measurements showed no statistical difference (P > 0.05). Conclusion This study shows that both central corneal thickness and stromal density are significant influential factors of reliable IOP readings. It is necessary to consider more corneal biomechanical properties, as well as exercise a high degree of caution in any new attempts towards adjusting an IOP-correction equation.

The utility of contact lens-assisted corneal cross-linking (CACXL) in progressive keratoconus patients with thin corneas

Purpose To evaluate efficacy and safety of contact lens-assisted corneal cross-linking (CACXL) among progressive keratoconus patients with thin corneas. Setting Private eye hospital Design Cross-sectional study Methods Thirty-six eyes of 36 consecutive patients with progressive keratoconus and thinnest corneal thickness of 380–400 µm after epithelium removal were included. CACXL was performed based on use of a dextran-free isotonic (>0.1%) riboflavin solution with hydroxypropyl methylcellulose (HPMC, 1.1%) after epithelial removal and placement of a riboflavin-soaked contact lens without an ultraviolet filter on the cornea and ultraviolet irradiance. Data on best distance corrected (CDVA) and uncorrected (UDVA) visual acuity, manifest sphere (D), manifest cylinder (D), K1 (D), K2 (D), mean keratometry (D) and Kmax (D) values, endothelial cell count and mean depth of demarcation line were recorded preoperatively and at the postoperative 1-year Results Post-operative 1-year data revealed significant increases in UDVA (0.23 ± 0.15 vs. 0.17 ± 0.13 D, p < 0.001) and CDVA (0.44 ± 0.18 vs. 0.36 ± 0.17 D, p < 0.001) values and a significant reduction in the mean Kmax (from 56 ± 3.3D to 55 ± 3.2 D, p < 0.001), K2 (from 49.7 ± 3.2 D to 49.52 ± 3.11 D, p = 0.049), manifest sphere (from −1.93 ± 2.21 D to −1.55 ± 2.02 D, p = 0.001) and manifest cylinder (from −2.83 ± 1.67 D to −2.39 ± 1.36 D, p < 0.001) values along with a similar endothelial cell count. The mean depth of demarcation line was mean 230 (SD17.05, range 200 to 262) at postoperative 1-month. Conclusions Our findings indicate favourable 1-year postoperative outcome of CACXL in progressive keratoconus patients with thin cornea in terms of improved visual acuity and keratectasia status as well as endothelial safety.

Evaluation of a novel combination of TRAM-34 and ascorbic acid for the treatment of corneal fibrosis in vivo

Corneal injury and aberrant wound healing commonly result in corneal fibrosis and subsequent vision loss. Intermediate-conductance calmodulin/calcium-activated K+ channels (KCa3.1) have been shown to promote fibrosis in non-ocular and ocular tissues via upregulation of transforming growth factor beta (TGFβ). TRAM-34 is a selective inhibitor of KCa3.1 and reduces fibrosis by downregulation of TGFβ-induced transdifferentiation of stromal fibroblasts to myofibroblasts. Ascorbic acid has been demonstrated to be effective in promoting corneal re-epithelialization and reduction of neovascularization via anti-VEGF and anti-MMP mechanisms. This study evaluates tolerability and efficacy of a novel combination of TRAM-34 (25μM) and ascorbic acid (10%) topical treatment for corneal fibrosis using an established in vivo rabbit model and conducting clinical eye examinations. Markers of corneal fibrosis were evaluated in all corneas at study endpoint via histopathology, immunofluorescence, and quantitative real-time PCR. The eyedrop treated eyes showed significantly improved clinical outcomes based on modified McDonald Shadduck scores, reduction of clinical haze on Fantes scores, and reduction of central corneal thickness (CCT). At cellular and molecular levels, eyedrop treatment also significantly reduced expression of alpha smooth muscle actin (α-SMA) mRNA and protein, collagen III mRNA, and fibronectin mRNA compared to non-treated eyes. Our study suggests that a tested new bimodal eyedrop is well tolerated and effectively reduces corneal fibrosis/haze in rabbits in vivo.

Descemet membrane endothelial keratoplasty: analysis of clinical outcomes of patients with 8–10 years follow-up

Purpose This study aimed to evaluate the clinical outcomes up to 10 years after Descemet membrane endothelial keratoplasty (DMEK). Methods In this retrospective, consecutive, single-center case series the medical files of eyes which have received DMEK between 2009 and 2012 for the treatment of endothelial dysfunction was evaluated regarding follow-up time and clinical outcomes. Annual examinations of best-corrected visual acuity (BCVA), endothelial cell density (ECD), central corneal thickness (CCT) of 66 eyes which fulfilled the criterion of a minimum of 8 years follow-up were analyzed. Results BCVA improved from 0.55 ± 0.37 logMAR (n = 54) to 0.15 ± 0.11 (n = 47) in eyes without ocular comorbidities one year after DMEK (p < 0.001), and remained stable up to 10 years after DMEK. Mean ECD decreased to 744 ± 207 cells/mm2 (n = 39) after 9 years, and to 729 ± 167 cells/mm2 (n = 21) after 10 years, respectively. CCT decreased from 650 ± 67 μm before DMEK to 525 ± 40 μm (n = 56) after 1 year, increasing slowly to 563 ± 40 µm (n = 39) after 9 years, and to 570 ± 42 µm (n = 21) after 10 years, respectively. Graft failure occurred in 4 of 66 eyes after year 8. These 4 eyes required repeat DMEK after 101–127 months. Conclusion This study shows the long-term outcomes in a small subset of DMEK grafts. Visual acuity remained stable in spite of slowly increasing corneal thickness and diminishing endothelial cell density during the 10-year period after DMEK.

Corneal Endothelial Changes Following Early Capsulotomy Using Neodymium:Yttrium-Aluminum-Garnet Laser

We aimed to survey whether the timing of neodymium:yttrium-aluminum-garnet (Nd:YAG) laser capsulotomy would alter the corneal endothelial morphology and density. A retrospective cohort study was conducted, and 48 patients with unilateral posterior capsular opacity (PCO) and Nd:YAG laser capsulotomy performance were enrolled. The participants were divided into the early Nd:YAG group (timing ≤ 12 months, n = 20) and late Nd:YAG group (timing > 12 months, n= 28) depending on elapsed months between phacoemulsification and Nd:YAG laser capsulotomy. Endothelial cell density (ECD), coefficient of variant (CV), hexagonality (HEX), and central corneal thickness (CCT) between the two groups were collected. A generalized estimate equation was conducted to evaluate the corneal endothelial parameters between the two groups with an adjusted odds ratio (aOR) and 95% confidence interval (CI). The CDVA was improved after treatment in both groups (both p < 0.001). Chronically, ECD in the early group was significantly decreased one week after treatment (2221.50 ± 327.73/mm2 vs. 2441.55 ± 321.80/mm2, p < 0.001), which recovered to 2369.95 ± 76.37/mm2 four weeks after the treatment but was still lower than the preoperative status (p < 0.001). In addition, the HEX percentage showed a significant reduction at four weeks after treatment (p = 0.028). The ECD in the early group was significantly lower than that in the late group (aOR: 0.167, 95% CI: 0.079–0.356, p = 0.003) in both week 1 (p < 0.001) and week 4 (p = 0.004) after laser treatment. In conclusion, the early application of Nd:YAG laser capsulotomy within one year after cataract surgery may be the reason for postoperative ECD decrement without known etiology.

Stabilization of refractive error and associated factors following small incision phacoemulsification cataract surgery

Background Accumulating evidence suggests that refractive stabilization occurs rapidly following small incision cataract surgery. Nonetheless, many guidelines still suggest waiting four to 6 weeks before prescribing corrective lenses. This study was undertaken to supplement the existing literature regarding refractive stabilization, and evaluate multiple contributing factors that could dissuade clinicians from confidently correcting refractive error in the early post-operative course following routine cataract surgeries. Methods Adult patients undergoing phacoemulsification cataract surgery with uncomplicated surgeries and post-surgical courses at the Calgary Ophthalmology Centre (Calgary, Alberta, Canada) were included in this prospective observational case series. Exclusion criteria included known corneal dystrophies, infectious keratitis, complicated surgery or toric/multifocal IOLs. Data was collected at weekly intervals for a total of 6 weeks. Collected data included autorefraction, visual acuity, corneal pachymetry, and effective lens position. Results One hundred six eyes of 104 patients were included in this study. Post-operative sphere, cylinder and spherical equivalent were not significantly different at any post-operative week compared with week six, and 80–86% of patients were within 0.5D of last follow-up spherical equivalent at any week. The secondary outcomes of central corneal thickness, effective lens position and visual acuity did, however, exhibit significant differences between early post-operative weeks and last follow-up values. Conclusions These data suggest that refractive error can be effectively measured and corrected as early as one-week post-operatively in the majority of patients, though other measures of post-operative stability including central corneal thickness, effective lens position and visual acuity can require up to 4 weeks to stabilize. Thus a conservative and pragmatic approach may be to wait until 4 weeks post-operatively prior to obtaining refractive correction following uncomplicated phacoemulsification cataract surgery.

Predictive factors of the accelerated transepithelial corneal cross-linking outcomes in keratoconus

Background This study aimed to evaluate the clinical outcomes and assess preoperative characteristics that may predict outcomes in keratoconus 1 year after accelerated transepithelial corneal cross-linking (ATE-CXL). Methods This prospective study included 93 eyes of 84 consecutive keratoconus patients with 1-year follow-up after ATE-CXL. Preoperative characteristics included corneal astigmatism, anterior chamber depth, anterior chamber volume, radius of curvature, posterior elevation, central corneal thickness (CCT), thinnest corneal thickness, steepest meridian keratometry, flattest meridian keratometry, and the maximum keratometry (Kmax). Data were obtained preoperatively and at 1, 3, 6, and 12 months postoperatively. The patient eyes were grouped into 3 subgroups according to CCT and Kmax values to observe the changes of keratoconus progression. Results All patients were successfully operated without complications at any follow-up time point. Mean changes of Kmax from baseline at 6 and 12 months were − 0.60 ± 2.21 D (P = 0.011) and − 0.36 ± 1.58 D (P = 0.030), respectively. Eyes with a thinner CCT and higher Kmax values exhibited a tendency for topographic flattening of ≥1.0 D (P = 0.003; P = 0.003). In the subgroup comparison, the Kmax values decreased significantly at 6 and 12 months after ATE-CXL in the group with CCT ≤ 450 μm (P = 0.018 and P = 0.045); the Kmax values of the group with Kmax > 65.0 D decreased significantly at 6 months postoperatively (P = 0.025). Conclusion ATE-CXL is a safe and effective treatment for keratoconus patients. Patients with thinner CCT and higher Kmax values are more likely to benefit from ATE-CXL.

Corneal Dystrophies

Corneal dystrophies have classically referred to inherited, bilateral disease without systemic findings, although there are several exceptions to this definition. Hereditary pattern is not present in most patients with epithelial basement membrane dystrophy (EBMD). Unilateral corneal changes may be found in some patients with posterior polymorphous corneal dystrophy (PPCD). TGFBI gene mutation (p.His572del) is associated with a unilateral, late-onset variant of lattice corneal dystrophy. Among all dystrophies, macular corneal dystrophy and posterior amorphous corneal dystrophy are associated with decreased corneal thickness. The International Committee for Classification of Corneal Dystrophies (IC3D) was created in 2005 to revise the corneal dystrophy nomenclature and create a current and accurate corneal dystrophy classification system. Evidential categories were created in the IC3D classification for reflecting the natural evolution of a corneal dystrophy and indicate the level of evidence supporting the existence of a given dystrophy.