FDA's role in expediting innovation of bioelectronic implants for vision restoration.

Bioelectronic implants for vision restoration are medical devices regulated in the United States by the Food and Drug Administration (FDA). This paper provides an overview of regulatory pathways and related FDA programs for bioelectronic implants for vision restoration, and identifies some of the gaps in the regulatory science of these devices. The FDA recognizes that additional discussion regarding development in this space is needed to further develop bioelectronic implants and ensure that safe and effective technologies are made available to patients with profound vision loss. FDA regularly participates in the Eye and the Chip World Research Congress meetings and continues to engage with important external stakeholders, including through public workshops such as the recent co-sponsored Expediting Innovation of Bioelectronic Implants for Vision Restoration. By participating in forums for discussion of these devices with all stakeholders, especially patients, FDA seeks to encourage advancement of these devices.

Symptoms and Satisfaction Levels Associated with Intraocular Lens Implants in the Monofocal and Premium IOL Patient-Reported Outcome Measure Study.

PURPOSE: To develop a questionnaire with standardized questions and images about visual symptoms and satisfaction administered before and after cataract surgery with monofocal and various (premium) intraocular lenses (IOLs). DESIGN: A prospective, observational study of cataract surgery patients completing a self-administered questionnaire preoperatively and postoperatively at 4 to 6 months. PARTICIPANTS: Five hundred fifty-four patients with plans to undergo implantation of the same IOL in both eyes on separate occasions in 20 ophthalmology practices. METHODS: An 86-item questionnaire with standardized images assessed the following 14 symptoms: glare, blurry vision, starbursts, hazy vision, snowballs, halos, floaters, double images, rings and spider webs, light flashes with eyes closed, distortion, light flashes with eyes open, shimmering images, and dark crescent-shaped shadows. MAIN OUTCOME MEASURES: Symptom severity and level of symptom bother, satisfaction with vision, quality of vision, and ability to see without corrective lenses or eyeglasses. RESULTS: Except for dark crescent-shaped shadows, the report of visual symptoms significantly decreased postoperatively. Best uncorrected binocular visual acuity improved from 0.47 (20/59 Snellen visual acuity values) ± 0.35 logarithm of the minimum angle of resolution (logMAR) preoperatively to 0.12 (20/26 Snellen visual acuity values) ± 0.12 logMAR postoperatively. Patients' ratings of intermediate vision as good to excellent improved significantly from 12% preoperatively to 71% postoperatively, and patients' ratings of distance vision improved from 8% preoperatively to 85% postoperatively. After surgery, 84% reported that they were somewhat, very, or completely satisfied with their vision. Most patients (88%) reported that they could see pretty well, very well, or perfectly well without corrective lenses after surgery. CONCLUSIONS: The Assessment of IntraOcular Lens Implant Symptoms questionnaire can be used across a wide variety of IOLs to evaluate visual symptoms and satisfaction with a growing segment of the market, premium IOLs, that target intermediate and near vision, in addition to distance vision. Compared to patients receiving monofocal IOLs, patients receiving premium IOLs appear to be more challenging to satisfy because of their requirements for distance, intermediate, and near vision, and their desire to be free of eyeglasses postoperatively. This instrument provides a structured, uniform tool for regulators, researchers, and ophthalmologists in everyday practice to gain insights into patients' experiences. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Development of a Patient-Reported Outcome Measure to Assess Symptoms Associated with Cataract Surgery and Intraocular Lens Implants.

PURPOSE: To develop a standardized patient-reported outcome measure of visual perceptions and symptoms for implanted premium and monofocal intraocular lenses (IOLs). DESIGN: Observational study before and after IOL implants to assess the measure and symptom experience. PARTICIPANTS: Adults scheduled for binocular implantation of the same IOL type completed the survey at baseline prior to surgery (n = 716) and postoperatively (n = 554). Most respondents were female (64%), White (81%), 61 or older (89%), and had some college or more education (62%). METHODS: Administration was by web survey with mail follow-up and phone reminders. MAIN OUTCOME MEASURES: Frequency, severity, and level of symptom bother in the last 7 days for 14 symptoms: (1) glare, (2) hazy vision, (3) blurry vision, (4) starbursts, (5) halos, (6) snowballs, (7) floaters, (8) double images, (9) rings and spider webs, (10) distortion, (11) light flashes with eyes closed, (12) light flashes with eyes open, (13) shimmering images, and (14) dark shadows. RESULTS: The median correlation among having 14 symptoms at baseline was only 0.19. Mean uncorrected binocular visual acuity improved from a preoperative value of 0.47 logarithm of the minimum angle of resolution (logMAR; Snellen 20/59) to a postoperative value of 0.12 (20/26) and best-corrected binocular visual acuity improved from 0.23 logMAR (20/34) preoperative to 0.05 logMAR (20/22) postoperative. The most bothersome symptoms were reduced after surgery: preoperative/postoperative glare (84%/36%), blurry vision (68%/22%), starbursts (66%/28%), hazy vision (63%/18%), snowballs (55%/17%), and halos (52%/22%). All symptoms decreased significantly (P < 0.0001) from before to after surgery except for dark crescent-shaped shadows (4%/4%). The percentage of symptoms rated as quite a bit or extremely bothersome declined from before to after surgery except for dark crescent-shaped shadows (29%/32%): blurry vision (54%/15%), snowballs (52%/14%), glare (49%/15%), and halos (46%/14%). Having monofocal IOL implants was associated with significantly more reduction in halos, starbursts, glare, and rings and spider webs, but less improvement in self-reported general vision. CONCLUSIONS: This study provides support for the 37-item Assessment of IntraOcular Lens Implant Symptoms (AIOLIS) instrument for use to assess symptoms and general perceptions of vision in clinical studies and clinical care. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Chronic hypertension increases aortic endothelial hydraulic conductivity by upregulating endothelial aquaporin-1 expression.

Numerous studies have examined the role of aquaporins in osmotic water transport in various systems, but virtually none have focused on the role of aquaporin in hydrostatically driven water transport involving mammalian cells save for our laboratory's recent study of aortic endothelial cells. Here, we investigated aquaporin-1 expression and function in the aortic endothelium in two high-renin rat models of hypertension, the spontaneously hypertensive genetically altered Wistar-Kyoto rat variant and Sprague-Dawley rats made hypertensive by two-kidney, one-clip Goldblatt surgery. We measured aquaporin-1 expression in aortic endothelial cells from whole rat aortas by quantitative immunohistochemistry and function by measuring the pressure-driven hydraulic conductivities of excised rat aortas with both intact and denuded endothelia on the same vessel. We used them to calculate the effective intimal hydraulic conductivity, which is a combination of endothelial and subendothelial components. We observed well-correlated enhancements in aquaporin-1 expression and function in both hypertensive rat models as well as in aortas from normotensive rats whose expression was upregulated by 2 h of forskolin treatment. Upregulated aquaporin-1 expression and function may be a response to hypertension that critically determines conduit artery vessel wall viability and long-term susceptibility to atherosclerosis.NEW & NOTEWORTHY The aortic endothelia of two high-renin hypertensive rat models express greater than two times the aquaporin-1 and, at low pressures, have greater than two times the endothelial hydraulic conductivity of normotensive rats. Data are consistent with theory predicting that higher endothelial aquaporin-1 expression raises the critical pressure for subendothelial intima compression and for artery wall hydraulic conductivity to drop.

Aquaporin-1 facilitates pressure-driven water flow across the aortic endothelium.

Aquaporin-1, a ubiquitous water channel membrane protein, is a major contributor to cell membrane osmotic water permeability. Arteries are the physiological system where hydrostatic dominates osmotic pressure differences. In the present study, we show that the walls of large conduit arteries constitute the first example where hydrostatic pressure drives aquaporin-1-mediated transcellular/transendothelial flow. We studied cultured aortic endothelial cell monolayers and excised whole aortas of male Sprague-Dawley rats with intact and inhibited aquaporin-1 activity and with normal and knocked down aquaporin-1 expression. We subjected these systems to transmural hydrostatic pressure differences at zero osmotic pressure differences. Impaired aquaporin-1 endothelia consistently showed reduced engineering flow metrics (transendothelial water flux and hydraulic conductivity). In vitro experiments with tracers that only cross the endothelium paracellularly showed that changes in junctional transport cannot explain these reductions. Percent reductions in whole aortic wall hydraulic conductivity with either chemical blocking or knockdown of aquaporin-1 differed at low and high transmural pressures. This observation highlights how aquaporin-1 expression likely directly influences aortic wall mechanics by changing the critical transmural pressure at which its sparse subendothelial intima compresses. Such compression increases transwall flow resistance. Our endothelial and historic erythrocyte membrane aquaporin density estimates were consistent. In conclusion, aquaporin-1 significantly contributes to hydrostatic pressure-driven water transport across aortic endothelial monolayers, both in culture and in whole rat aortas. This transport, and parallel junctional flow, can dilute solutes that entered the wall paracellularly or through endothelial monolayer disruptions. Lower atherogenic precursor solute concentrations may slow their intimal entrainment kinetics.