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  • ABVC BioPharma, 80

  • Acanthamoeba, 30

  • acetazolamide, 318, 319

  • acrylic intraocular lenses, 55

  • active pharmaceutical ingredient (API), 401

  • adeno-associated viruses (AAVs), 262, 430–431

    • AAV-2-based vector, 434

  • adenoviruses, 262

  • adhesion molecules (AMs), 271

  • adipic dihydrazide (ADH), 80

  • Advanced Therapy Medicinal Products (ATMPs), 192

  • aflibercept microspheres, 367

  • age-related macular degeneration (AMD), 9, 353–354

  • aldehyde-modified hyaluronan, 82

  • AlexaFluor-647, 84

  • alginate–poly(l-lysine)-coated collagen composites, 371

  • AlloDerm, 300

  • alpha-smooth muscle actin (α-SMA), 52

  • alumina, 400

  • aluminium oxide, 163

  • amniotic membranes, 330–331

  • animal-derived tissues, 300–301

  • anterior capsular opacification (ACO), 59, 60

  • anterior-segment drug delivery, 311

    • barriers and challenges to, 312–314

    • eye drop-based drug delivery

      • conventional eye drops, 314–317

      • nanoparticle eye drops, 317–320

      • prodrugs and soft drugs, 320–321

    • iontophoresis, 331

      • delivery of dexamethasone, 334

      • delivery of riboflavin, 334–335

    • material-based

      • amniotic membranes, 330–331

      • contact lenses, 322–326

      • intracameral inserts, 329–330

      • ocular surface inserts, 326–328

      • punctal plugs, 328–329

  • Antheraea mylitta, 210

  • antimicrobial lenses, 27

  • anti-programmed cell death ligand 1 (anti-PDL1), 361

  • anti-VEGF drugs, 10

  • aqueous humor, 5

  • arginyl–glycyl–asparatic acid (RGD), 271

  • artificial full-thickness corneas, 213–215

  • astigmatism, 8

  • augmented vision/reality, 39

  • auricular cartilage, 292–295

  • autologous materials, 157

  • Avastin®, 361

  • azobenzenes, 426

  • bacterial quorum-sensing systems, 35

  • bacteriorhodopsin (BR), 126–127

  • BAK (benzalkonium chloride), 316

  • balanced saline solution (BSS), 73

  • benzoyl peroxide, 54

  • besifloxacin, 318, 408

  • bevacizumab, 362

  • bifocal rigid gas-permeable lenses, 36

  • bi-layered PCL–chitosan implant, 374

  • bioactive agents, 271

  • Bio-Alcamid®, 77

  • bioceramic implants, 158–159

  • biodegradable OCPs, 113

  • bioengineering of tarsus, 301–304

  • biohybrid scaffold materials, 274–275

  • bio-interfacing array, 101–102

  • biomaterials, defined, 11, 194

  • biosynthetic stromal substitutes, 207

  • bipolar cells, 351

  • blink sensors, 38

  • blood–retinal barrier (BRB), 353, 355

  • blow-fill-seal technology (BFS), 316–317

  • Bombyx mori, 210

  • Bowman’s layer. See epithelial basement membrane

  • brain-derived neurotrophic factors (BDNF), 368

  • brimonidine, 319

  • Brimonidine Drug Delivery System (Brimo DDS®), 374

  • Bruch’s membrane, 272, 273, 352

  • 1,4-butanediol diglycidyl ether (BDDE), 80

  • caffeic acid, 365

  • calcium hydroxylapatite (CaHA), 162

  • Calhoun Vision, Inc., 64

  • Canada, regulatory framework in, 455

    • cell and gene therapy products, 457–459

    • combination products, 459–460

    • medical devices, 455–457

  • carbonic anhydrase inhibitors, 315–316

  • carbon nanotubes (CNTs), 104, 118–122

  • carbon nanovesicles, 362

  • carboxymethyl cellulose (CMC), 368

  • carboxymethylchitosan (CMCTS), 81

  • carteolol, 318

  • cataracts, 8–9, 48

    • drug delivery for cataract patients, 60–61

    • and treatments, 48–51

  • CD44, 421

  • cell and gene therapy products (CGTPs), 457–459, 465–466

    • definitions of, 445–446

    • manufacturing facility requirements, 448

    • quality management systems (QMS) requirements for manufacturers of, 447–448

    • regulatory frameworks for, 446–447

  • cell-based therapies of cornea, 208. See also retinal regeneration and repair, cell-based therapies for

    • extracellular vesicles (EVs), 212–213

    • therapeutic cell cultivation, biomaterials for, 212

    • therapeutic cell delivery

      • natural biomaterials for, 209–211

      • synthetic scaffolds for, 211–212

  • cell scaffolds

    • natural biomaterials as, 273

    • synthetic biomaterials as, 273–274

  • cell therapy products (CTPs), 457–458

  • CEP290 gene, 265

  • ceramic implants, 157–158

  • ceramics, 400–401

  • chitosan, 209–210, 265, 315, 411

  • chitosan–collagen hydrogel scaffolds, 210

  • chitosan-grafted PNIPAAm hydrogels, 371

  • cholera toxin B (CTB), 421–422

  • cholesterol, 264

  • chondromucosal grafts, 295

  • choroid, 6

  • choroidal neovascularization (CNV), 9

  • CI26, 211

  • ciliary body, 5

  • ciliary muscles, 49

  • ciprofloxacin, 318

  • clear lens epithelial cells, 6

  • coated MNs, 404

  • collagen, 4, 273

  • collagen-like peptides (CLP), 216

  • composite biomaterials, 196

  • composite materials, 160

  • computer-aided design (CAD), 186

  • conductive hydrogels, 130

  • conjunctiva, 25, 217

    • cell sources and culture techniques, 219–220

  • conjunctival autograft, 219

  • conjunctival cells, 222

  • conjunctival epithelial cells, 223

    • for tissue-engineered conjunctival constructs, 219

  • conjunctival epithelial substitute, 220

    • biological substrates for, 221–223

    • synthetic substrates for, 223

  • contact lens discomfort (CLD), 30–32

  • contact lens dropout, 33–34

  • contact lenses, 322–326, 375–376

    • care system components, 23

    • indications for wear

      • lens care systems, 22

      • medical uses, 20

      • refractive error, 19–20

      • rigid lens use, 21–22

      • soft lens use, 20–21

    • materials

      • historical perspective, 14–16

      • material requirements, 13–14

      • regulation and classification, 16–19

    • -related complications, 28

      • corneal infection, 29–30

      • corneal inflammation, 28–29

    • types of, 14

    • unintended ocular effects of, 22

      • corneal sensitivity, 28

      • elastic modulus, 23–24

      • lens movement and tear exchange, 24–25

      • oxygen transmissibility, 26

      • spoilation/deposition, 26–27

      • subclinical inflammation, 27

      • tribology (frictional effects), 25

    • user challenges with, 30

      • adherence, 34–35

      • handling, 33

      • vision, 32–33

  • contact lenses, future opportunities with, 35

    • augmented vision/reality, 39

    • drug delivery and theranostics, 38–39

    • to improve vision

      • customised optics for diseased eyes, 36

      • low-vision enhancements, 36

      • myopia control, 35

      • presbyopia, accommodative lenses for, 35–36

    • ocular and systemic disease, diagnosis and screening for, 36

      • diabetes, 36–37

      • dry eye disease (DED), 37–38

      • glaucoma, 37

  • contact lens-induced dry eye (CLIDE), 25

  • contact lens papillary conjunctivitis (CLPC), 26

  • contemporary contact lens materials, 16

  • controlled drug-delivery system, 61

  • controlled-release strategies for intraocular lenses, 61–64

  • conventional eye drops, 314–317

  • CoreNeat KPro, 214

  • cornea, 3, 4–5, 204, 331

    • artificial corneas, 213–215

    • cell-based therapies, 208

      • biomaterials for therapeutic cell cultivation, 212

      • extracellular vesicles (EVs), 212–213

      • natural biomaterials for therapeutic cell delivery, 209–211

      • synthetic scaffolds for therapeutic cell delivery, 211–212

    • cell-free biomaterials stimulating in situ tissue regeneration

      • entering clinical realm, 215–216

      • fully-defined synthetic implants promoting regeneration, 216–217

      • injectable hydrogels, 217

    • cellular layers of

      • corneal endothelial replacement, 208

      • corneal epithelium and limbus, 206–207

      • stromal replacement, 207–208

  • cornea, strategies to replace and regenerate, 190

    • artificial corneas, 213–215

    • biomaterial fabrication technologies, 194

      • fabrication techniques for corneal and anterior segment repair, 197–202

      • injectable biomaterials, 202–203

      • nanotechnologies and composites, 203–204

      • regenerative medicine and tissue engineering applications, biomaterials for, 194–197

    • cell-based therapies, 208–213

    • cell-free biomaterials stimulating in situ tissue regeneration, 215–217

    • cell sources and culture techniques, 219–220

    • conjunctiva, 217

    • conjunctival epithelial substitute, 220

      • biological substrates for, 221–223

      • synthetic substrates for, 223

    • corneal endothelial replacement, 208

    • corneal epithelium and limbus, 206–207

    • regenerative medicine strategies, 192

      • ex vivo versus in situ tissue engineering, biomaterials in, 193–194

      • gene transfer, biomaterials and, 192–193

      • stem cells and cell derivatives, biomaterials for, 193

    • stromal replacement, 207–208

    • tissue replacement, anterior segment need for, 191–192

    • trabecular meshwork (TM), 223

      • regeneration, 224–226

      • structure and function, 224

    • translational aspects

      • emerging regenerative therapies, regulatory framework for clinical use of, 228–229

      • preclinical to clinical development, challenges moving from, 226–228

  • corneal and anterior segment repair

    • biomaterials in, 196–197

    • fabrication techniques for, 197–202

  • corneal collagen crosslinking procedures, 334

  • corneal endothelial cells (CECs), 208, 209, 212

  • corneal endothelial replacement, 208

  • corneal endothelium, 4, 26

  • corneal epithelium and limbus, 206–207

  • corneal infection, 29–30

  • corneal inflammation, 28–29

  • corneal mesenchymal stem cell exosomes, 213

  • corneal sensitivity, with contact lenses, 28

  • corneal transparency, 5

  • COVID-19 pandemic, 194

  • COVID-19 vaccines, 258

  • CRISPR-associated protein 9 (Cas9) enzyme, 259

  • cryolite glass, 159

  • crystalline lens, 5

  • crystallin proteins, 49

  • curcumin-loaded nanomicelles, 359

  • customised optics for diseased eyes, 36

  • cyclodextrins, 315

  • cyclosporine A, 318

  • decellularized extracellular matrix (dECM), 222, 272–273

  • decellularized tissues, 210

  • Deep Orbital Sub-Q Restylane injections, 162

  • dehydroepiandrosterone (DHEA), 421

  • delivery technologies, 356

    • contact lenses, 375–376

    • hydrogel technology, 369–373

    • implants, 373–375

    • microtechnology, 364–369

    • nanotechnology, 357–364

  • dendrimers, 319

  • dendritic-like cells, 27

  • denuded amniotic membranes (dAMs), 272

  • deposition, on contact lenses, 26–27

  • deprotonation, 422

  • dermis fat graft (DFG), 157

  • Descemet’s membrane (DM), 4, 208, 210, 272

  • dexamethasone, 318

    • iontophoresis delivery of, 334

  • dexa-methasone–peptide conjugates (Dex–PC), 370

  • diabetes, 36–37

  • diabetic macular edema (DME), 354

  • diabetic retinopathy (DR), 7, 9, 354, 359

  • diagnostic/theranostic smart materials, 428–431

  • diamond, 127–129

  • diffractive intraocular lenses, 50

  • diffusion-controlled release systems, 62

  • 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, 264

  • dipivefrin, 321

  • diseased eyes, customised optics for, 36

  • dissolution-controlled release systems, 61–62

  • dissolved oxygen, 3

  • dissolving MNs, 405–409

  • double-strand break (DSB), 260

  • double-stranded RNA (dsRNA), 259

  • drug delivery

    • anterior segment. See anterior-segment drug delivery

    • with intraocular lenses

      • cataract patients, drug delivery for, 60–61

      • controlled-release strategies for IOLs, 61–64

    • and theranostics, 38–39

  • drug-eluting contact lenses, 374

  • drug-loaded nanoparticles, 63

  • drug product (DP), 447

  • drug-releasing contact lenses, 38

  • drug substance (DS), 447

  • drusen, 9

  • dry AMD, 9

  • dry eye disease (DED), 4, 37–38

  • E-cadherin, 53

  • edetate disodium (EDTA), 316

  • EDIT-101 (Editas Medicine), 265

  • elastic modulus, of contact lenses, 23–24

  • electroretinography (ERG), 81, 358

  • electrospinning, 274

  • Elschnig’s pearls, 51

  • embryonic stem cells (ESCs), 267–268

  • encapsulating drugs, 318

  • EndoArt®, 211

  • endogenously controlled smart materials, 420–424

  • endophthalmitis, 61

  • endothelial pump, 5

  • ENDURAGen, 300

  • enucleation and evisceration, orbital implants after. See orbital implants after enucleation and evisceration

  • epidermal growth factor (EGF), 52

  • epithelial basement membrane, 4

  • epithelial-to-mesenchymal transition (EMT), 52, 53

  • 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), 215

  • European Union, regulatory framework in, 460

    • advanced therapy medicinal products, 461–462

    • combination products, 462–463

    • expedited programs, 463

    • medical devices, 460–461

  • exogenously stimulated smart materials, 424–428

  • exosomes, 212, 213

  • extended depth of focus (EDF), 36, 50

  • extracellular matrix (ECM), 194, 210, 352

  • extracellular vesicles (EVs), 212–213, 362–363

  • ex vivo versus in situ tissue engineering, biomaterials in, 193–194

  • eye

    • anatomy and physiology of, 1

      • ciliary body, 5

      • cornea, 3, 4–5

      • iris, 5

      • lens, 5–6

      • neural retina, 6–7

      • Schlemm’s canal, 5

      • tear film, 1–4

      • vitreous humor, 6

    • general anatomy of, 2

  • eye drop-based drug delivery

    • conventional eye drops, 314–317

    • nanoparticle eye drops, 317

      • dendrimers, 319

      • liposomes, 318

      • nanosuspensions and nanoemulsions, 320

      • niosomes, 318–319

      • polymeric nanocarriers, 318

      • solid lipid nanoparticles, 319–320

    • prodrugs and soft drugs, 320–321

  • EyeGate II drug-delivery system, 334

  • eyelid anatomy, 288–289

  • EyeLief® system, 371

  • eye-related conditions and statistics, 7–10

  • fabrication technologies, biomaterial

    • for corneal and anterior segment repair, 196–202

    • injectable biomaterials, 202–203

    • nanotechnologies and composites, 203–204

    • ophthalmic applications, requirements for biomaterials intended for, 196

  • far sightedness. See hyperopia

  • fibrin, 209

  • fibroblast growth factor (FGF), 52

  • fibrosis, 60

  • fibrotic opacification, 52

  • Fick’s laws of diffusion, 62

  • first-generation silicone hydrogel lenses, 24

  • fluorescein angiography (FA), 428

  • fluorescein isothiocyanate–ovalbumin (FITC-OVA) NP-loaded MN, 407

  • 5-fluorouracil, 360

  • foldable capsular vitreous body (FCVB), 76

  • foreign-body responses (FBRs), 101

  • fornix, 154–155

  • free flaps, 176

  • Frost, W. A., 151

  • Fuchs endothelial corneal dystrophy (FECD), 208

  • Fusarium, 30

  • gangciclovir, 318

  • ganglion cell layer (GNL), 87

  • GelCORE, 203

  • gene addition, 259

  • gene delivery, 258

    • biomaterials for, 261

      • non-viral vectors, 263–265

      • viral vectors, 262–263

    • developments, 265–266

    • future directions, 266

    • types of, 259–261

  • gene editing, 259–261

  • gene silencing, 259

  • gene-therapy classifications, 469

  • gene-therapy clinical trials, 470

  • gene-therapy manufacturing, 469–470

  • gene transfer, biomaterials and, 192–193

  • geographic atrophy (GA), 9, 354

  • glaucoma, 5, 9, 37, 257, 355

  • glaucoma drainage devices (GDDs), 433

  • glaucoma shunt/stent, 9

  • glial cell-derived neurotrophic factor (GDNF), 365, 368

  • glial cells, 122

  • glycoprotein mucins, 3

  • glycosaminoglycans, 4, 5, 6

  • glycidic methacrylate-modified HA (GMHA) hydrogels, 80

  • (3-glycidyloxypropyl)trimethoxysilane (GOPS) crosslinker, 118

  • goblet-associated passages (GAPs), 218

  • gold nanospheres, 430

  • Good Manufacturing Practices (GMP), 412

  • Gore synthetic cornea, 214

  • Graves ophthalmopathy, 300

  • green electronics. See organic bioelectronics

  • GS030 (GenSight Biologics), 265, 266

  • gypsum-based mold, 181

  • hard palate mucoperiosteum, 291–292

  • hepatocyte growth factor (HGF), 52

  • hermetic encapsulation, 100

  • hollow MNs, 404–405

  • human amniotic membrane, 209

  • human amniotic membrane powder (HAMP), 274

  • human ESC (hESC), 267

  • human iPSC (hiPSC), 267

  • human leukocyte antigen (HLA), 267

  • human tissues, 297–300

  • human umbilical tissue-derived cells (hUTCs), 269

  • human umbilical vein endothelial cells (HUVECs), 361

  • hyalocytes, 6

  • hyaluronan (HA)-oxime, development of, 83

  • hyaluronan, 315. See also hyaluronic acid

  • hyaluronic acid (HA), 6, 264, 273, 315

  • hybrid contact lenses, 13

  • hydrogel contact lens polymers, 15

  • hydrogel lenses, 56

  • hydrogels, 129–130, 162, 369–373

    • chitosan-grafted PNIPAAm hydrogels, 371

    • conductive, 130

    • injectable, 217

    • poly(vinyl alcohol) (PVA)-based, 76

  • hydrogen peroxide-based systems, 22

  • hydrophobically-modified poly(ethylene glycol) (HM-PEG), 64

  • 2-hydroxy-2-methylpropiophenone, 54

  • hydroxyapatite (Hap), 158, 163

  • hydroxyethylmethacrylate (HEMA), 14

  • hydroxypropylchitosan (HPCTS), 81

  • hyperopia, 8

  • hyperopic eye, 8

  • hypoxia, 28

    • short term, 26

  • IBE-814 IVT, 369

  • Iluviens®, 373

  • immunoglobulin G (IgG), 362

  • implants, 373–375

  • indium-tin oxide (ITO)-coated glass substrate, 114

  • induced pluripotent stem cell-derived TM cell (iPSC-TM), 224

  • induced pluripotent stem cells (iPSCs), 209, 267, 468

    • -derived tissue classification, 468

    • -derived tissue clinical trials, 469

    • -derived tissue manufacturing, 468–469

  • inflammatory cells, 52

  • infrared imaging, 25

  • inherited retinal degenerations (IRDs), 356

  • injectable biomaterials, 202–203

  • injectable hydrogels, 217

  • injectable lenses, 64

  • inner nuclear layer (INL), 87

  • insulin-like growth factor-1 (IGF-1), 372

  • integrated (porous) and non-integrated (non-porous) orbital implants, 160–162

  • integrated materials, 157

    • bioceramic implants, 158–159

    • ceramic implants, 157–158

    • hydroxyapatite (Hap) implants, 158

    • porous polyethylene (PE), 159

  • internal limiting membrane (ILM), 350

  • interocular pressure (IOP), 37

  • intracameral inserts, 329–330

  • intraocular lenses (IOLs), 48, 49

    • advanced, 64–65

    • cataracts and treatments, 48–51

    • drug delivery with

      • for cataract patients, 60–61

      • controlled-release strategies for IOLs, 61–64

    • material composition, 54

      • bulk properties, 56

      • polymers, 54–56

    • posterior capsular opacification (PCO)

      • lens epithelium and phenotypic changes that result in, 51–53

      • risk factors, 53–54

    • strategies to improve

      • material properties’ influence on PCO in clinical studies, 57–58

      • surface modification, 58–59

    • surface properties, 57

  • intraocular pressure (IOP), 5, 9, 224, 356, 433

  • in vivo confocal microscopy, 28

  • in vivo laser confocal imaging, 27

  • ionizable cationic lipid (ICL), 263–264

  • iontophoresis, 331

    • delivery of dexamethasone, 334

    • delivery of riboflavin, 334–335

  • iris, 5

  • I-vation™, 373

  • keratin films, 210

  • keratoprostheses (KPro), 213

  • lacrimal functional unit, 3

  • lactoferrin, 4, 319

  • Ladd, Anna Coleman, 184

  • laser capsulotomy, 51

  • laser treatment/surgery, 9

  • latanoprost, 318

  • late-stage dry AMD. See geographic atrophy

  • Leber congenital amaurosis (LCA), 258

  • Leber hereditary optic neuropathy (LHON), 374

  • lens, 5–6

  • lens care systems, 22

  • lens epithelial cells (LECs), 49, 53

  • lid-parallel conjunctival folds (LIPCOF), 25

  • lid-wiper epitheliopathy (LWE), 25

  • light-activated protein films, 126–127

  • limbal stem cell deficiency (LSCD), 206–207, 212, 213

  • limbus, 25, 206–207

  • lipid-based vectors, 263

  • lipid layer of tear film, 3

  • lipid nanoparticles (LNPs), 263

  • Lipiview® interferometer, 25

  • lipopolysaccharide (LPS)

  • liposomal cationic lipids, 263

  • liposomes, 318

  • LiQD Cornea, 203, 217

  • liquid crystal polymers (LCPs), 64, 103, 104–107

  • long-acting ocular drug delivery using MNs, 409–411

  • loteprednol etabonate, 321

  • lower critical solution temperature (LCST), 274, 425

  • low-vision enhancements, 36

  • lutein–graphene oxide nanosheets, 360

  • Luxturna®, 265, 430

  • lymphocyte-derived microparticles (LMPs), 368

  • lysozyme, 4, 26

  • macromer, 64

  • magnetic resonance imaging (MRI) systems, 427

  • material-based anterior-segment drug delivery

    • amniotic membranes, 330–331

    • contact lenses, 322–326

    • intracameral inserts, 329–330

    • ocular surface inserts, 326–328

    • punctal plugs, 328–329

  • Mati Therapeutics, 329

  • matrix-controlled/monolithic diffusion systems, 62

  • matrix metalloproteases (MMPs), 81

  • matrix metalloproteinases, 4

  • medical devices

    • definitions of, 448–449

    • facility requirements, manufacturing, 454–455

    • quality management systems (QMS) requirements for manufacturers, 451–454

    • sub-classification of, 449–451

  • medium-chain triglycerides (MCTs), 81

  • meibomian glands, 3

  • membrane-controlled diffusion systems, 62

  • mercaptophenylboronic acid (MPBA), 65

  • mesenchymal stem cells (MSCs), 224–225, 267, 363, 430

    • and human umbilical tissue-derived cells, 268–269

  • messenger RNA (mRNA), 259

  • metal–organic frameworks (MOFs), 430

  • methacrylated hyaluronic acid (MeHA), 367

  • 2-methacryoloyloxyethyl phosphorylcholine (MPC), 216

  • microbes, 182

  • microbubbles, 431

  • microelectrode array (MEA), 98

  • microelectromechanical systems (MEMS), 401

  • microelectronic microsystems (MEMS), 433

  • microneedle (MN), 367, 399

    • barriers to commercialisation and future perspectives, 412–413

    • long-acting ocular drug delivery using, 409–411

    • material types and fabrication techniques, 400–402

    • for ocular delivery, 399–400

    • strategies to facilitate intraocular drug delivery using, 402

      • coated MNs, 404

      • dissolving MNs, 405–409

      • hollow MNs, 404–405

  • microphotodiode array (MPDA), 98

  • microRNA, 259

  • microtechnology, 364–369

  • minimum effective concentration (MEC), 61

  • minimum toxic concentration (MTC), 61

  • MIRAgel (MAI), 76

  • modulus of elasticity. See Young’s modulus

  • monofocal intraocular lenses, 49–50

  • moulding, 197

  • mucoadhesive compounds, 315

  • Mules, P. H., 151

  • Mules sphere, 151

  • multi-dose eye drops, 316

  • multifocal-design soft contact lenses, 35

  • myopia, 8

  • myopia control, 35

  • myopic eye, 8

  • Müller glial cells (MCs), 256, 269–270

  • nanoemulsions, 320

  • nanomaterials

    • carbon nanotubes (CNTs), 118–122

    • nanowires (NWs), 123–126

  • nanoparticle eye drops, 317

    • dendrimers, 319

    • liposomes, 318

    • nanosuspensions and nanoemulsions, 320

    • niosomes, 318–319

    • polymeric nanocarriers, 318

    • solid lipid nanoparticles, 319–320

  • nanospheres, 264–265

  • nanostructured lipid carriers (NLCs), 358–359, 362

  • nanosuspensions, 320

  • nanotechnologies, 357–364

    • and composites, 203–204

  • nanowires (NWs), 123–126

  • nasal septal chondromucosa, 295–296

  • natamycin, 318, 319

  • natural biomaterials, 194

    • as cell scaffolds, 273

    • for therapeutic cell delivery, 209–211

  • natural polymers, 75, 265, 371

    • substitutes based on, 80–82

  • nearsightedness. See myopia

  • neural retina, 6–7

  • neuronal death, 257

  • N-hydroxysuccinimide (NHS), 215

  • niosomes, 318–319

  • nitrogen-doped ultra-nanocrystalline diamond (N-UNCD) electrodes, 128

  • non-integrating implants, grafts and wrapping, 159–160

  • non-pegged implants, 161

  • non-pharmaceutical smart materials, 431–434

  • non-polysaccharide natural polymers, 81

  • non-proliferative DR, 9

  • non-viral vectors, 263–265

  • N-phenylacrylamide (NPA), 79

  • nutrient transport, 3

  • N-vinylpyrrolidinone (NVP), 80

  • ocular and facial prostheses, modern biomaterials usage in, 173

    • intraoperative considerations, 175–178

    • orbital prosthesis, using, 182–183

    • postoperative considerations, 178–179

    • pre-exenteration decision making, 174–175

    • prosthesis fabrication, 179–182

    • realistic prostheses, historical review and advances in, 183–186

  • ocular and systemic disease, diagnosis and screening for, 36

    • diabetes, 36–37

    • dry eye disease (DED), 37–38

    • glaucoma, 37

  • ocular coherence tomography (OCT), 87

  • ocular drug delivery, microneedle approaches to, 399–400

    • barriers to commercialisation and future perspectives, 412–413

    • long-acting ocular drug delivery using MNs, 409–411

    • microneedle (MN) manufacture, 400–402

    • strategies to facilitate, 402

      • coated MNs, 404

      • dissolving MNs, 405–409

      • hollow MNs, 404–405

  • ocular oxygen, 3

  • ocular surface inserts, 326–328

  • ofloxacin, 319

  • ophthalmic applications, smart materials in, 419

    • diagnostic/theranostic smart materials, 428–431

    • endogenously controlled smart materials, 420–424

    • exogenously stimulated smart materials, 424–428

    • future perspectives, 435

    • non-pharmaceutical smart materials, 431–434

  • ophthalmic materials, considerations for, 10

  • ophthalmic prodrug, 320

  • optical coherence tomography (OCT), 268, 428

  • optic nerve, 356

  • optic neuropathy, 356

  • optogenetics, 265

  • orbital implants after enucleation and evisceration, 150–152

    • autologous materials, 157

    • complications, implant-related, 163

    • composite materials, 160

    • implant exposure, extrusion, and infection, 155–156

    • implant migration, 153–154

    • implant motility, 154–155

    • integrated (porous) and non-integrated (non-porous) orbital implants, 160–162

    • integrated materials, 157

      • bioceramic implants, 158–159

      • ceramic implants, 157–158

      • hydroxyapatite (Hap) implants, 158

      • porous polyethylene (PE), 159

    • mental health, viewpoint on, 164–165

    • non-integrating implants, grafts and wrapping, 159–160

    • non-surgical alternatives, 162–163

    • paediatric patient, 164

    • pegging to enhance orbital motility, 163–164

  • orbital implant volume, 152–153

  • orbital prosthesis, using, 182–183

  • organic bioelectronics, 113

  • organic conducting polymers (OCPs), 103–104, 107, 113

    • thiophene-based, 114–118

  • orthokeratology, 35

  • ortho-nitrobenzyl (o-NB), 427

  • osmolarity, 316

  • osseointegrative implants, 175, 177

  • outer nuclear layer (ONL), 87

  • ovalbumin (OVA), 411

  • overnight lens wear, 29

  • oxidative stress, 359

  • oxime-crosslinked hyaluronan as a vitreous substitute

    • hyaluronan (HA)-oxime, development of, 83

    • in vivo biocompatibility, 85–87

    • in vivo stability, 84–85

    • oxime ligation as a crosslinking strategy, 82

    • physical characterization, 83–84

    • retinal function, assessment of, 87–88

  • oxygen transmissibility, of contact lenses, 26

  • Ozurdex®, 373

  • palisades of Vogt, 206

  • pars plana vitrectomy (PPV), 73

  • parylene, 274

  • Paré, Ambroise, 183

  • PEDOT polymerisation, 120

  • pegging, 163–164

  • PEGylated microemulsion, 366

  • PEGylation, 264

  • penetratin, 264

  • penetrating keratoplasty (PK), 194, 205

  • perfluorocarbon liquids (PFCLs), 73

  • pericranial periosteum, 296–297

  • phenolic and cellulose plastics, 184

  • phospholipids, 263, 264

  • photic artifacts, 50

  • photoreceptors (PRs), 256

  • pigment epithelial-derived factor (PEDF), 372

  • pilocarpine, 315, 319

  • pinocembrin, 365

  • plaster-like gypsum-based material is, 179

  • plasticized poly(vinyl chloride), 184

  • pleomorphism, 26

  • pluripotent stem cells, 267–268

  • poly(2-hydroxylethyl acrylate) (PHEA), 76

  • poly(3,4-ethylenedioxythiophene) (PEDOT), 107, 113

  • poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx), 302

  • poly(acrylamide-co-bisacryloylcystamine) (AAm-co-BAC), 79

  • polyamidoamine (PAMAM), 360

  • poly(benzyl glutamate) (PBG), 274

  • polydimethyl siloxane (PDMS), 184, 273, 193, 367, 401

  • poly(ε-caprolactone) (PCL), 196, 223, 274

  • polyethylene, 104, 274

  • polyethylene glycol (PEG), 58, 430, 196

  • polyethyleneimine (PEI), 265, 363, 366

  • polyglactin mesh, 160

  • poly(glycerol sebacate) (PGS), 274

  • polylactic acid (PLA), 196, 411

  • poly(lactic-co-glycolic acid) (PLGA), 196, 223, 271, 274, 411

  • poly(l-lactic acid), 223

  • poly(l-lysine) (PLL), 265

  • polymegethism, 26

  • polymeric encapsulation, 104

  • polymeric materials, 104

  • polymeric micro-/nanoparticles, 411

  • polymeric nanocarriers, 318

  • polymeric nanoparticles, 264, 411

  • polymeric orbital implant (PMOI), 159

  • polymeric vitreous substitutes, 75

    • crosslinking methods, 75–76

    • natural polymers, 75

    • synthetic polymers, 75

  • polymers, 54–56

  • poly(methacrylamide-co-methacrylate-co-N,N'-bismethacryloylcystamine) (MAM-co-MAA-co-BMAC), 79

  • poly(methacrylate-co-2-hydroxyethyl acrylate), 76

  • poly(methyl methacrylate) (PMMA), 14, 48, 156, 159, 184

  • poly(N-acryloyl glycinamide-co-carboxybetaine acrylamide) co-polymer (PNAGA-PCBAA), 128

  • poly(N-isopropylacrylamide) (pNIPAAm) polymer, 212, 274

  • polypeptide (PEP), 430

  • polyphenols, 365

  • poly(propylene fumarate), 302

  • poly(pyrrole), 107

  • poly[(R)-3-hydroxybutyrate-(R)-3-hydroxyhexanoate] (PHBH), 80

  • POLYRETINA device, 117–118

  • polysaccharide, 315

  • poly(sodium styrene sulfonate) (PSS), 366

  • poly(tetrafluoroethylene), 223

  • poly(thiophene), 107

  • polyurethane, 104

  • poly(vinyl alcohol) (PVA), 196

    • -based hydrogels, 76

  • polyvinyl alcohol (PVA)–chitosan hydrogel, 365

  • porous polyethylene (PE), 159, 163, 301

  • positron emission tomography (PET), 428

  • posterior capsular opacification (PCO), 9, 51

    • lens epithelium and phenotypic changes that result in, 51–53

    • material properties’ influence on, 57–58

    • risk factors, 53–54

  • posterior lamellar grafts, indications for the use of, 289

  • posterior segment anatomy, 349–353

  • posterior-segment pathology and available treatments, 353–356

  • pre-exenteration decision making, 174–175

  • presbyopia, 6, 8

    • accommodative lenses for, 35–36

    • -correcting IOLs, 50

  • preservative-free multidose (PFMD) dispensers, 316

  • pressure regulation, in eye, 5

  • primary open angle glaucoma (POAG), 329

  • prodrugs and soft drugs, 320–321

  • proliferative diabetic retinopathy, 9

  • proliferative vitreoretinopathy (PVR), 355

  • pro-regenerative injectable hydrogels, 217

  • prostaglandin F2 alpha receptor (PGF) analogues, 321

  • prosthesis fabrication, 179–182

  • protamine sulfate (PRM), 368

  • protospacer adjacent motif (PAM), 260

  • Pseudomonas aeruginosa, 29

  • pseudophakic bullous keratopathy, 208

  • punctal plugs, 328–329

  • Pykus Therapeutics, 79

  • quality control (QC) testing, 412

  • quality management systems (QMS) requirements, for manufacturers, 447–448, 451–454

  • rapamycin, 360

  • reactive oxygen species (ROS), 360

  • realistic prostheses, historical review and advances in, 183–186

  • recombinant human type III (RHCIII), 215

  • refractive error, 19–20

  • refractive index (RI), 56

  • regenerative medicine strategies, 192

    • ex vivo versus in situ tissue engineering, biomaterials in, 193–194

    • gene transfer, biomaterials and, 192–193

    • stem cells and cell derivatives, biomaterials for, 193

  • regenerative stromal substitutes, 207

  • regulatory agencies, aims of, 445

  • regulatory framework for the clinical use of emerging regenerative therapies, 455

    • Canada, 455

      • cell and gene therapy products, 457–459

      • combination products, 459–460

      • medical devices, 455–457

    • European Union, 460

      • advanced therapy medicinal products, 461–462

      • combination products, 462–463

      • expedited programs, 463

      • medical devices, 460–461

    • United States of America, 463

      • cell and gene therapy products, 465–466

      • combination products, 466

      • expedited programs, 466–467

      • medical devices, 464–465

  • regulatory pathway, 444

    • cell and gene therapy products (CGTP)

      • definitions of, 445–446

      • manufacturing facility requirements, 448

      • quality management systems (QMS) requirements for manufacturers of, 447–448

      • regulatory frameworks for, 446–447

    • gene therapies targeting genetic diseases

      • gene-therapy classifications, 469

      • gene-therapy clinical trials, 470

      • gene-therapy manufacturing, 469–470

    • medical devices

      • definitions of, 448–449

      • facility requirements, manufacturing, 454–455

      • quality management systems (QMS) requirements for manufacturers, 451–454

      • sub-classification of, 449–451

    • retinal iPSC-derived products, 468

      • iPSC-derived tissue classification, 468

      • iPSC-derived tissue clinical trials, 469

      • iPSC-derived tissue manufacturing, 468–469

  • retina, 6–7

  • retinal degenerative diseases, 257

  • retinal function, assessment of, 87–88

  • retinal ganglion cells (RGCs), 97, 256, 268, 351, 366, 421

  • retinal implants, emerging biomaterials for, 97

    • diamond, 127–129

    • future directions, 130–132

    • hydrogels, 129–130

    • light-activated protein films, 126–127

    • liquid crystal polymers, 104–107

    • nanomaterials

      • carbon nanotubes (CNTs), 118–122

      • nanowires (NWs), 123–126

    • organic conducting polymers (OCPs), 107

      • thiophene-based, 114–118

    • visual prostheses, desirable properties and challenges for the biomaterials of, 100–103

  • retinal iPSC-derived products, 468

    • iPSC-derived tissue classification, 468

    • iPSC-derived tissue clinical trials, 469

    • iPSC-derived tissue manufacturing, 468–469

  • retinal neurogenesis and cell sources for retinal regeneration, 266

    • embryonic and pluripotent stem cells, 267–268

    • mesenchymal stem cells (MSCs) and human umbilical tissue-derived cells, 268–269

    • Müller glial cells and retinal progenitor cells, 269–270

  • retinal pigment epithelium (RPE), 6–7, 76, 256, 351, 353–354, 355, 421

  • retinal progenitor cells (RPCs), 269–270, 363

  • retinal regeneration and repair, cell-based therapies for, 266

    • retinal neurogenesis and cell sources, 266

      • embryonic and pluripotent stem cells, 267–268

      • mesenchymal stem cells (MSCs) and human umbilical tissue-derived cells, 268–269

      • Müller glial cells and retinal progenitor cells, 269–270

    • tissue engineering, 270

      • bioactive agents, 271

      • biohybrid scaffold materials, 274–275

      • decellularized extracellular matrix (dECM) scaffold, 272–273

      • natural biomaterials as cell scaffolds, 273

      • scaffold-free cell sheets, 275–276

      • synthetic biomaterials as cell scaffolds, 273–274

  • retinal scleral buckle, 301

  • retinal vein occlusion (RVO), 359

  • retinitis pigmentosa (RP), 97, 258

  • Retisert®, 373

  • retroviruses, 262

  • riboflavin, 302

    • iontophoresis delivery of, 334–335

  • Ridley, Harold, 49

  • rigid contact lenses, 13, 19

  • rigid gas-permeable lenses, 14, 24

  • rigid lens use, 21–22

  • rigid plastics, 184

  • Ripple Therapeutics, 369

  • RNA-induced silencing complex (RISC), 259

  • RNA interference (RNAi), 259

  • robust hermetic encapsulation, 100

  • RTC-1119, 369

  • rubber latex, 184

  • scaffold architecture, 272

  • scaffold characteristics, ideal, 271

    • biohybrid scaffold materials, 274–275

    • decellularized extracellular matrix (dECM) scaffold, 272–273

    • natural biomaterials as cell scaffolds, 273

    • scaffold-free cell sheets, 275–276

    • synthetic biomaterials as cell scaffolds, 273–274

  • scaffold-free cell sheets, 275–276

  • Schlemm’s canal, 5

  • secreted protein, acidic and rich in cystine (SPARC), 373

  • semi-fluoronated alkanes (SFAs), 73

  • short hairpin RNA (shRNA), 259

  • silicone, 15, 104, 156, 159–160, 181, 184

  • silicone elastomer, 401

  • silicone hydrogel contact lens, 15, 16

  • silicone oils, 73

  • silicone rubber, 184

  • silicon nanoparticles (SiNPs), 428

  • silicon nanowires, 104

  • silk fibroin (SF), 115–116, 222, 223, 275

  • siloxane hydrogel lenses, 211

  • small interfering RNA (siRNA), 259

  • smart biomaterials, 197

  • smart materials in ophthalmic applications, 419

    • diagnostic/theranostic smart materials, 428–431

    • endogenously controlled smart materials, 420–424

    • exogenously stimulated smart materials, 424–428

    • future perspectives, 435

    • non-pharmaceutical smart materials, 431–434

  • Soemmerring’s ring, 52

  • soft contact lenses, 14–15, 18, 20–21, 23, 24

  • soft drugs, 320–321

  • soft hydrophilic acrylic IOLs, 56

  • soft hydrophobic acrylic IOLs, 55

  • solid lipid nanoparticles, 319–320

  • spoilation, of contact lenses, 26–27

  • sporadic Creutzfeldt–Jakob disease, 160

  • Stargardt macular dystrophy (SMD), 258

  • stem cells, 206

  • stem cells and cell derivatives, biomaterials for, 193

  • Stevens–Johnson syndrome, 295

  • stromal function, 4

  • stromal replacement, 207–208

  • subclinical inflammation, from contact lenses, 27

  • superior epithelial arcuate lesions (SEALs), 24

  • suprachoroidal space (SCS), 405

  • Susvimo™, 373

  • synthetic biomaterials, 195

    • as cell scaffolds, 273–274

  • synthetic materials, 301

  • synthetic orbital hydroxyapatite implants, 158

  • synthetic polymers, 75

    • substitutes based on, 76–80

  • synthetic scaffolds for therapeutic cell delivery, 211–212

  • tarsal plate substitutes in modern reconstructive plastic surgery of eyelids, 287

    • animal-derived tissues, 300–301

    • auricular cartilage, 292–295

    • hard palate mucoperiosteum, 291–292

    • human tissues, 297–300

    • nasal septal chondromucosa, 295–296

    • normal eyelid anatomy, 288–289

    • pericranial periosteum, 296–297

    • posterior lamellar grafts, indications for the use of, 289

    • synthetic materials, 301

  • tarsal substitutes, 289–291

  • tarsus

    • bioengineering of, 301–304

    • unique characteristics of, 288–289

  • TarSys, 300

  • tauroursodeoxycholic acid (TUDCA), 365

  • tear film, 1–4

  • tear-fluid glucose monitoring by contact lens, 36–37

  • theranostics, 38–39, 428–431

  • therapeutic cell cultivation, biomaterials for, 212

  • therapeutic cell delivery

    • natural biomaterials for, 209–211

    • synthetic scaffolds for, 211–212

  • therapeutic products and implications, classification of, 445

    • cell and gene therapy products (CGTPs)

      • definitions of, 445–446

      • manufacturing facility requirements, 448

      • quality management systems (QMS) requirements for manufacturers of, 447–448

      • regulatory frameworks for, 446–447

    • medical devices

      • definitions of, 448–449

      • manufacturing facility requirements, 454–455

      • quality management systems (QMS) requirements for manufacturers, 451–454

      • sub-classification of, 449–451

  • thermoplastic polyurethanes, 184

  • thiol-crosslinked polymers, 79

  • thiophene-based conjugate polymers, 114–118

  • 3D bioprinting, 201

  • 3D-printed ocular and maxillofacial prostheses, 186

  • timolol, 319

  • tissue classification, iPSC-derived, 468

  • tissue clinical trials, iPSC-derived, 469

  • tissue-derived extracellular matrix, 221

  • tissue-engineered conjunctival constructs

    • conjunctival epithelial cells for, 219

  • tissue engineering, 270, 301

    • bioactive agents, 271

    • scaffold characteristics, ideal, 271

      • biohybrid scaffold materials, 274–275

      • decellularized extracellular matrix (dECM) scaffold, 272–273

      • natural biomaterials as cell scaffolds, 273

      • scaffold-free cell sheets, 275–276

      • synthetic biomaterials as cell scaffolds, 273–274

  • tissue manufacturing, iPSC-derived, 468–469

  • tissue replacement, anterior segment need for, 191–192

  • tissue scaffolds, 271

  • titaminates, 223

  • toluidine blue, 430

  • toric intraocular lenses, 50

  • trabecular meshwork (TM), 223, 430

    • regeneration, 224–226

    • structure and function, 224

  • trabecular meshwork stem cell (TMSCs), 224

  • transcription activator-like effector nucleases (TALENs), 260

  • transforming growth factor beta (TGF-β), 52, 53

  • Triggerfish contact lens sensor, 37

  • tropicamide, 319

  • tumor necrosis factor-α (TNF-α), 366

  • ultrasound or photoacoustic imaging (US/PAI), 428

  • ultraviolet light, 6

  • United States of America, regulatory framework in, 463

    • cell and gene therapy products, 465–466

    • combination products, 466

    • expedited programs, 466–467

    • medical devices, 464–465

  • upper critical solution temperature (UCST), 425

  • uveitis, 354

  • vascular endothelial growth factor (VEGF), 354

  • vinyl and styrene plastics, 184

  • viral vectors, 262–263

  • vision, lenses to improve

    • customised optics for diseased eyes, 36

    • low-vision enhancements, 36

    • myopia control, 35

    • presbyopia, accommodative lenses for, 35–36

  • vision loss, 9

  • vision loss, drug delivery to the posterior segment to combat, 349

    • background, 349

      • posterior segment anatomy, 349–353

      • posterior-segment pathology and available treatments, 353–356

    • delivery technologies, 356

      • contact lenses, 375–376

      • hydrogel technology, 369–373

      • implants, 373–375

      • microtechnology, 364–369

      • nanotechnology, 357–364

    • future directions, 382–383

    • opportunities and challenges, 376–382

  • visual function, 1

  • visual prostheses, desirable properties and challenges for the biomaterials of, 100–103

  • visual prosthesis, 98

  • Vitraserts®, 373

  • vitrectomies in vitreoretinal surgery, 73

  • vitreoretinal surgery, vitrectomies in, 73

  • vitreous body substitute (VBS), 81

  • vitreous humor, 6, 72–73

  • vitreous substitutes, 72

    • currently-used, 73–74

    • future directions, 88

    • in vivo studies, reports of, 76

      • natural polymers, substitutes based on, 80–82

      • synthetic polymers, substitutes based on, 76–80

    • oxime-crosslinked hyaluronan as

      • hyaluronan (HA)-oxime, development of, 83

      • in vivo biocompatibility, 85–87

      • in vivo stability, 84–85

      • oxime ligation as a crosslinking strategy, 82

      • physical characterization, 83–84

      • retinal function, assessment of, 87–88

    • polymeric vitreous substitutes, 75

      • crosslinking methods, 75–76

      • natural polymers, 75

      • synthetic polymers, 75

    • properties of, 74

      • biological properties, 74

      • chemical properties, 74

      • manufacturing properties, 75

      • physical properties, 74–75

  • wear, contact lens indications for

    • lens care systems, 22

    • medical uses, 20

    • refractive error, 19–20

    • rigid lens use, 21–22

    • soft lens use, 20–21

  • wet AMD, 9

  • Young’s modulus, 101

  • Yutiq™, 373

  • zinc finger nucleases (ZFNs), 260

  • zinc finger proteins (ZFPs), 260

  • zonule fibres, 6

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