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An estimated 95 million people worldwide are affected by cataract. Cataract still remains the leading cause of blindness in middle-income and low-income countries. With the advancement of surgical technology and techniques, cataract surgery has evolved to small-incisional surgery with rapid visual recovery, good visual outcomes, and minimal complications in most patients. With the development of advanced technology in intraocular lenses, the combined treatment of cataract and astigmatism or presbyopia, or both, is possible. Paediatric cataracts have a different pathogenesis, surgical concerns, and postoperative clinical course from those of age-related cataracts, and the visual outcome is multifactorial and dependent on postoperative visual rehabilitation. New developments in cataract surgery will continue to improve the visual, anatomical, and patient-reported outcomes. Future work should focus on promoting the accessibility and quality of cataract surgery in developing countries.

Recent literature has ascribed that the paracrine action of stem cells is mediated by exosomes. Exosomes are nano-sized extracellular vesicles (30 to 100 nm) of endocytic origin that play important roles in intercellular communication. They have the ability to deliver various therapeutic effects, e.g., skin regeneration or cardiac function recovery, when applied topically or injected systemically. However, injection of exosomes has been shown to result in rapid clearance from blood circulation and accumulation of the exosomes in the liver, spleen, lung, and gastrointestinal tract can be found as early as 2 h after injection. Topical administration of exosomes on the skin or ocular surface would suffer the same fate due to rapid fluid turnover (sweat or tears). Biodegradable or highly porous hydrogels have been utilized to load exosomes and to deliver a sustained therapeutic effect. They can also prevent the exosomes from being cleared prematurely and allow the delivery of a more localized and concentrated exosome dosage by placing the hydrogel directly at or in the proximity of the target site. In this mini-review, we elaborate on the challenges of conventional exosome administration and highlight the solution to the shortcomings in the form of exosome-incorporated hydrogels. Different techniques to encapsulate exosomes and examples of hydrogels that have been used to create sustained delivery systems of exosomes are also discussed.

High-order diffraction (HOD) from optical microstructures is undesirable in many applications because of the accompanying ghosting patterns and loss of efficiency. In contrast to suppressing HOD with subwavelength structures that challenge the fabrication of large-scale devices, managing HOD is less developed due to the lack of an efficient method for independently manipulating HOD. Here, we report independent manipulation of HODs, which are unexploited for subdiffraction-limit focusing in diffractive lenses, through an analytical formula that correlates the diffraction order and the width of each zone. The large spatial frequencies offered by the HODs enable our lenses to reduce the lateral focal size down to 0.44  λ even without any subwavelength feature (indispensable in most high- NA diffractive lenses), facilitating large-scale manufacture. Experimentally, we demonstrate high-order lens-based confocal imaging with a center-to-center dry resolution of 190 nm, the highest among visible-light confocal microscopies, and laser-ablation lithography with achieved direct-writing resolution of 400 nm (0.385  λ ). The authors introduce the independent manipulation of high-order diffraction with a high-order diffractive lens for sub-diffraction limit focusing in confocal microscopy and laser ablation lithography.

Consistent expansion of human corneal endothelial cells (hCECs) is critical in the development of tissue engineered endothelial constructs. However, a wide range of complex culture media, developed from different basal media have been reported in the propagation of hCECs, some with more success than others. These results are further confounded by donor-to-donor variability. The aim of this study is to evaluate four culture media in the isolation and propagation of hCECs isolated from a series of paired donor corneas in order to negate donor variability. Isolated primary hCECs were cultured in four previously published medium coded in this study as: M1-DMEM; M2-OptiMEM-I; M3-DMEM/F12, & M4-Ham's F12/M199. Primary hCECs established in these conditions were expanded for two passages and analyzed for (1) their propensity to adhere and proliferate; (2) their expression of characteristic corneal endothelium markers: Na+K+/ATPase and ZO-1; and (3) their cellular morphology throughout the study. We found that hCECs isolated in all four media showed rapid attachment when cultured on FNC-coated dishes. However, hCECs established in the four media exhibited different proliferation profiles with striking morphological differences. Corneal endothelial cells cultured in M1 and M3 could not be propagated beyond the first and second passage respectively. The hCECs cultured in M2 and M4 were significantly more proliferative and expressed markers characteristics of human corneal endothelium: Na+K+/ATPase and ZO-1. However, the unique morphological characteristics of cultivated hCECs were not maintained in either M2 or M4 beyond the third passage.The proliferative capacity and morphology of hCECs are vastly affected by the four culture media. For the development of tissue engineered graft materials using cultured hCECs derived from the isolation methodology described in this study, we propose the use of proliferative media M2 or M4 up to the third passage, or before the cultured hCECs lose their unique cellular morphology.

Keratoconus is the most common corneal ectatic disorder. It is characterized by progressive corneal thinning with resultant irregular astigmatism and myopia. Its prevalence has been estimated at 1:375 to 1:2,000 people globally, with a considerably higher rate in the younger populations. Over the past two decades, there was a paradigm shift in the management of keratoconus. The treatment has expanded significantly from conservative management (e.g., spectacles and contact lenses wear) and penetrating keratoplasty to many other therapeutic and refractive modalities, including corneal cross-linking (with various protocols/techniques), combined CXL-keratorefractive surgeries, intracorneal ring segments, anterior lamellar keratoplasty, and more recently, Bowman’s layer transplantation, stromal keratophakia, and stromal regeneration. Several recent large genome-wide association studies (GWAS) have identified important genetic mutations relevant to keratoconus, facilitating the development of potential gene therapy targeting keratoconus and halting the disease progression. In addition, attempts have been made to leverage the power of artificial intelligence-assisted algorithms in enabling earlier detection and progression prediction in keratoconus. In this review, we provide a comprehensive overview of the current and emerging treatment of keratoconus and propose a treatment algorithm for systematically guiding the management of this common clinical entity.

Background Persistent epithelial defects (PED), associated with limbal stem cell deficiency (LSCD), require ocular surface reconstruction with a stable corneal epithelium (CE). This study investigated CE reformation using human adipose mesenchymal stem cells (ADSC), which derived epithelial progenitors via mesenchymal-epithelial transition (MET). Methods STEMPRO human ADSC were cultured with specific inhibitors antagonizing glycogen synthase kinase-3 and transforming growth factor-β signaling, followed by culture under a defined progenitor cell targeted-epithelial differentiation condition to generate epithelial-like cells (MET-Epi), which were characterized for cell viability, mesenchymal, and epithelial phenotypes using immunofluorescence and flow cytometry. Tissue-engineered (TE) MET-Epi cells on fibrin gel were transplanted to corneal surface of the rat LSCD model caused by alkali injury. Epithelial healing, corneal edema, and haze grading, CE formation were assessed by fluorescein staining, slit lamp bio-microscopy, anterior segment optical coherence tomography, and immunohistochemistry. Results CD73 high /CD90 high /CD105 high /CD166 high /CD14 negative /CD31 negative human ADSC underwent MET, giving viable epithelial-like progenitors expressing δNp63, CDH1 (E-cadherin), epidermal growth factor receptor, integrin-β4, and cytokeratin (CK)-5, 9. Under defined epithelial differentiation culture, these progenitors generated MET-Epi cells expressing cell junction proteins ZO1 and occludin. When transplanted onto rat corneal surface with LSCD-induced PED, TE-MET-Epi achieved more efficient epithelial healing, suppressed corneal edema, and opacities, when compared to corneas without treatment or transplanted with TE-ADSC. CE markers (CK3, 12, and CDH1) were expressed on TE-MET-Epi-transplanted corneas but not in other control groups. Conclusion Human ADSC-derived epithelial-like cells, via MET, recovered the CE from PED associated with LSCD. ADSC can be a viable adult stem cell source for potential autologous epithelial cell-based therapy for corneal surface disorders.

The purpose of this study was to evaluate corneal epithelium and stromal remodelling with anterior segment optical coherence tomography in patients who have undergone stromal lenticule addition keratoplasty (SLAK) for advanced keratoconus. This was a prospective non-comparative observational study. Fifteen eyes of 15 patients with advanced keratoconus underwent implantation with a cadaveric, donor negative meniscus-shaped intrastromal lenticule, produced with a femtosecond laser, into a stromal pocket dissected in the recipient cornea at a depth of 120 μm. Simulated keratometry, central corneal thickness (CTT), corneal thinnest point (CTP), central epithelial thickness (CET), central and peripheral lenticule thickness, anterior and posterior stromal thickness were measured. Regional central corneal epithelial thickness (CET) and variations in the inner annular area (IAT) and outer annular area (OAT) were also analysed. All parameters were measured preoperatively and 1, 3, and 6 months postoperatively. The average anterior Sim-k decreased from 59.63 ± 7.58 preoperatively to 57.19 ± 6.33 D 6 months postoperatively. CCT, CTP, CET, and OAT increased and IAT decreased significantly after 1 month. All parameters appeared unchanged at 6-months except that of OAT that further increased. Lenticule thickness was stable. In conclusion we observed that SLAK reshapes the cornea by central flattening with stromal thickening and epithelial thickness restoration.

Small incision lenticule extraction (SMILE) becomes a procedure to correct myopia. The extracted lenticule can be used for other clinical scenarios. To prepare for allogeneic implantation, lenticule decellularization with preserved optical property, stromal architecture and chemistry would be necessary. We evaluated different methods to decellularize thin human corneal stromal lenticules created by femtosecond laser. Treatment with 0.1% sodium dodecylsulfate (SDS) followed by extensive washes was the most efficient protocol to remove cellular and nuclear materials. Empty cell space was found inside the stroma, which displayed aligned collagen fibril architecture similar to native stroma. The SDS-based method was superior to other treatments with hyperosmotic 1.5 M sodium chloride, 0.1% Triton X-100 and nucleases (from 2 to 10 U/ml DNase and RNase) in preserving extracellular matrix content (collagens, glycoproteins and glycosaminoglycans). The stromal transparency and light transmittance was indifferent to untreated lenticules. In vitro recellularization showed that the SDS-treated lenticules supported corneal stromal fibroblast growth. In vivo re-implantation into a rabbit stromal pocket further revealed the safety and biocompatibility of SDS-decellularized lenticules without short- and long-term rejection risk. Our results concluded that femtosecond laser-derived human stromal lenticules decellularized by 0.1% SDS could generate a transplantable bioscaffold with native-like stromal architecture and chemistry.

Restoration of vision due to corneal blindness from corneal endothelial dysfunction can be achieved via a corneal transplantation. However, global shortage of donor tissues has driven the development cell-based therapeutics. With the capacity to propagate regulatory compliant human corneal endothelial cells (CEnCs), this study evaluated the functionality of propagated CEnCs delivered via tissue-engineered endothelial keratoplasty (TE-EK) or corneal endothelial cell injection (CE-CI) within a rabbit model of bullous keratopathy. For animals with TE-EK grafts, central corneal thickness (CCT) increased to >1000 μm post-operatively. Gradual thinning with improvements in corneal clarity was observed from week 1. CCT at week 3 was 484.3 ± 73.7 μm. In rabbits with CE-CI, corneal clarity was maintained throughout, and CCT at week 3 was 582.5 ± 171.5 μm. Control corneas remained significantly edematous throughout the study period compared to their respective experimental groups ( p  < 0.05). Characterization of excised corneas showed a monolayer with heterogeneously shaped CEnCs in both TE-EK and CE-CI groups. Immunohistochemistry demonstrated reactivity to anti-human specific nuclei antibody attributing corneal recovery to the functional human CEnCs. This study showed that regulatory compliant cell-based therapy for corneal endothelial dysfunction can be delivered by both TE-EK and CE-CI, and holds great promise as an alternative to traditional corneal transplantation.