Electron beam-irradiated donor cornea for on-demand lenticule implantation to treat corneal diseases and refractive error.

The cornea is the major contributor to the refractive power of the eye, and corneal diseases are a leading cause of reversible blindness. The main treatment for advanced corneal disease is keratoplasty: allograft transplantation of the cornea. Examples include lenticule implantation to treat corneal disorders (e.g. keratoconus) or correct refractive errors. These procedures are limited by the shelf-life of the corneal tissue, which must be discarded within 2-4 weeks. Electron-beam irradiation is an emerging sterilisation technique, which extends this shelf life to 2 years. Here, we produced lenticules from fresh and electron-beam (E-beam) irradiated corneas to establish a new source of tissue for lenticule implantation. In vitro, in vivo, and ex vivo experiments were conducted to compare fresh and E-beam-irradiated lenticules. Results were similar in terms of cutting accuracy, ultrastructure, optical transparency, ease of extraction and transplantation, resilience to mechanical handling, biocompatibility, and post-transplant wound healing process. Two main differences were noted. First, ∼59% reduction of glycosaminoglycans resulted in greater compression of E-beam-irradiated lenticules post-transplant, likely due to reduced corneal hydration-this appeared to affect keratometry after implantation. Cutting a thicker lenticule would be required to ameliorate the difference in refraction. Second, E-beam-sterilised lenticules exhibited lower Young's modulus which may indicate greater care with handling, although no damage or perforation was caused in our procedures. In summary, E-beam-irradiated corneas are a viable source of tissue for stromal lenticules, and may facilitate on-demand lenticule implantation to treat a wide range of corneal diseases. Our study suggested that its applications in human patients are warranted. STATEMENT OF SIGNIFICANCE: Corneal blindness affects over six million patients worldwide. For patients requiring corneal transplantation, current cadaver-based procedures are limited by the short shelf-life of donor tissue. Electron-beam (E-beam) sterilisation extends this shelf-life from weeks to years but there are few published studies of its use. We demonstrated that E-beam-irradiated corneas are a viable source of lenticules for implantation. We conducted in vitro, in vivo, and ex vivo comparisons of E-beam and fresh corneal lenticules. The only differences exhibited by E-beam-treated lenticules were reduced expression of glycosaminoglycans, resulting in greater tissue compression and lower refraction suggesting that a thicker cut is required to achieve the same optical and refractive outcome; and lower Young's modulus indicating extra care with handling.

Incisional surface quality of electron-beam irradiated cornea-extracted lenticule for stromal keratophakia: high nJ-energy vs. low nJ-energy femtosecond laser.

Introduction: Corneal lenticules can be utilized as an additive material for stromal keratophakia. However, following extraction, they must be reimplanted almost immediately or cryopreserved in lenticule banks. Electron-beam (E-beam) irradiated corneas permit room-temperature storage for up to 2 years, enabling keratophakia to be performed on demand. This study aims to compare the performance of high nano Joule (nJ)-energy (VisuMax) and low nJ-energy (FEMTO LDV) femtosecond laser systems on the thickness consistency and surface quality and collagen morphology of lenticules produced from fresh and E-beamed corneas. Methods: A total of 24 lenticules with -6.00 dioptre power were cut in fresh human donor corneas and E-beamed corneas with VisuMax and FEMTO LDV. Before extraction, the thickness of the lenticules was measured with anterior segment-optical coherence tomography (AS-OCT). The incisional surface roughness of extracted lenticules was analyzed using atomic force microscopy (AFM) and scanning electron microscopy (SEM). Multiphoton microscopy was then used to assess the surface collagen morphometry. Results: The E-beamed lenticules that were cut using FEMTO LDV were significantly thicker than the fresh specimens as opposed to those created with VisuMax, which had a similar thickness as the fresh lenticules. On the vertex, they were ∼11% thicker than the fresh lenticules. The surface roughness (Rq) of E-beamed lenticules incised with FEMTO LDV did not differ significantly from the fresh lenticules. This contrasted with the VisuMax-fashioned lenticules, which showed notably smoother surfaces (∼36 and ∼20% lower Rq on anterior and posterior surfaces, respectively) on the E-beamed than the fresh lenticules. The FEMTO LDV induced less cumulative changes to the collagen morphology on the surfaces of both fresh and E-beamed lenticules than the VisuMax. Conclusion: It has been previously demonstrated that the low nJ-energy FEMTO LDV produced a smoother cutting surface compared to high nJ-energy VisuMax in fresh lenticules. Here, we showed that this effect was also seen in the E-beamed lenticules. In addition, lower laser energy conferred fewer changes to the lenticular surface collagen morphology. The smaller disparity in surface cutting quality and collagen disturbances on the E-beamed lenticules could be beneficial for the early visual recovery of patients who undergo stromal keratophakia.

Attitudes and Knowledge Concerning Corneal Donation in a Population-Based Sample of Urban Chinese Adults.

PURPOSE: To better understand knowledge and attitudes concerning corneal donation among Chinese adults. METHODS: Randomly selected residents in predetermined age strata 20 to 60+ years completed home-based questionnaires in each of 12 randomly chosen communities in Guangzhou, southern China. RESULTS: Among 1217 selected persons, 430 (35.3%) completed the questionnaires (mean age 40.4 yrs, 57.9% female). Refusers were older (44.8 yrs, P < 0.001), but sex did not differ (52.2% female, P = 0.07). Among participants, 175 (40.7%) were willing to donate their corneas (WTD). Differences between WTD and not WTD included donation knowledge score (range, 1-12) [WTD (SD) 6.91 ± 2.21, not WTD 5.62 ± 2.43, P < 0.001]; having discussed donation (WTD 26.3%, not WTD 8.63%, P < 0.001); viewing donation as unpopular (WTD 88.0%, not WTD 96.5%, P = 0.001); and feeling donation "damages the body" (WTD 15.4%, not WTD 25.7%, P = 0.013). Associated significantly with WTD in multiple regression models were higher knowledge score [odds ratio (OR) = 1.18, 95% confidence interval (CI), 1.04-1.32, P = 0.008]; not feeling donation "damages the body" (OR = 1.91, 95% CI, 1.07-3.43, P = 0.030); and willingness to discuss donation (OR = 10.6, 95% CI, 3.35-33.9, P < 0.001). WTD did not differ by age (>60 yrs: 22/51, 43.1%; ≤60 yrs: 153/379, 40.4%, P = 0.706). Assuming all those refusing the survey would not donate, 14.4% (175/1217) were WTD for themselves, though only 7.1% (86/1217) would do so on behalf of a family member if they did not know the deceased's preference. CONCLUSIONS: Interventions to increase knowledge and promote discussions about donation, and policies allowing widespread expression of donation preference, are needed in this setting.

Brief Report: Chimpanzee Social Responsiveness Scale (CSRS) Detects Individual Variation in Social Responsiveness for Captive Chimpanzees.

Comparative studies of social responsiveness, a core impairment in autism spectrum disorder (ASD), will enhance our understanding of typical and atypical social behavior. We previously reported a quantitative, cross-species (human-chimpanzee) social responsiveness measure, which included the development of the Chimpanzee Social Responsiveness Scale (CSRS). Here, we augment our prior CSRS sample with 25 zoo chimpanzees at three sites: combined N = 54. The CSRS demonstrated strong interrater reliability, and low-ranked chimpanzees, on average, displayed higher CSRS scores. The CSRS continues to discriminate variation in chimpanzee social responsiveness, and the association of higher scores with lower chimpanzee social standing has implications for the relationship between autistic traits and human social status. Continued comparative investigations of social responsiveness will enhance our understanding of underlying impairments in ASD, improve early diagnosis, and inform future therapies.

Initial description of a quantitative, cross-species (chimpanzee-human) social responsiveness measure.

OBJECTIVE: Comparative studies of social responsiveness, an ability that is impaired in autism spectrum disorders, can inform our understanding of both autism and the cognitive architecture of social behavior. Because there is no existing quantitative measure of social responsiveness in chimpanzees, we generated a quantitative, cross-species (human-chimpanzee) social responsiveness measure. METHOD: We translated the Social Responsiveness Scale (SRS), an instrument that quantifies human social responsiveness, into an analogous instrument for chimpanzees. We then retranslated this "Chimpanzee SRS" into a human "Cross-Species SRS" (XSRS). We evaluated three groups of chimpanzees (n = 29) with the Chimpanzee SRS and typical and human children with autism spectrum disorder (ASD; n = 20) with the XSRS. RESULTS: The Chimpanzee SRS demonstrated strong interrater reliability at the three sites (ranges for individual ICCs: 0.534 to 0.866; mean ICCs: 0.851 to 0.970). As has been observed in human beings, exploratory principal components analysis of Chimpanzee SRS scores supports a single factor underlying chimpanzee social responsiveness. Human subjects' XSRS scores were fully concordant with their SRS scores (r = 0.976, p = .001) and distinguished appropriately between typical and ASD subjects. One chimpanzee known for inappropriate social behavior displayed a significantly higher score than all other chimpanzees at its site, demonstrating the scale's ability to detect impaired social responsiveness in chimpanzees. CONCLUSION: Our initial cross-species social responsiveness scale proved reliable and discriminated differences in social responsiveness across (in a relative sense) and within (in a more objectively quantifiable manner) human beings and chimpanzees.