Impact of Calcium and Phosphorus Levels on Optical Deterioration in Primary and Secondary Intraocular Lens Calcification.

Purpose: The purpose of this study was to investigate the impact of calcium and phosphorus levels on optical deterioration in primary and secondary intraocular lens (IOL) calcification. Methods: A total of 18 explanted IOLs, 10 with primary, and 8 with secondary calcification, were examined. Straylight and light loss were evaluated as predictors of optical impairment. The individual amount of calcium and phosphorus was determined using thermogravimetry followed by emission spectroscopy (ICP-OES). The relationship between calcification and optical impairment was investigated. Results: Primary calcified IOLs contained significantly higher amounts of calcium and phosphorus compared to secondary calcified IOLs (calcium P < 0.02 and phosphorus P < 0.01), translating to greater light loss and significantly higher straylight mean values. In secondary calcification, light loss and straylight were highly dependent on calcium (r² = 0.90, P < 0.001 and r² = 0.70, P < 0.01) and phosphorus (r² = 0.66 and r² = 0.65, both P < 0.02), whereas these correlations were much lower in primary calcification (all r = 0.25, P > 0.05). Conclusions: ICP-OES is the first methodology to precisely assess the calcium and phosphorus content in IOL calcification thus based on mass ratios allowing improved molecular characterization. Primary calcification showed higher amounts of calcium and phosphorus, translating to higher straylight and light loss and thus a higher risk for impairment of visual quality than secondary calcification. Translational Relevance: This study is the first to quantify calcification and demonstrate the relationship to optical deterioration in IOLs, substantially contributing to understand how visual impairment arises in patients with calcified IOLs.

In Vitro Physicochemical and Pharmacokinetic Properties of Bevacizumab Dissolved in Silicone Oils Compared to Hydrogel-Substitutes and Porcine Vitreous Bodies.

Anti-VEGF agents, e.g., bevacizumab, are used in retinal surgery, while their interaction with silicone oils and novel hydrogels remains unclear. This study examines the in vitro pharmacokinetics of bevacizumab in silicone oil-filled eyes compared to various hydrogel replacements and the porcine vitreous body as well as its impact on the interface tension of silicone oils. An in vitro model filled with light or heavy silicone oil, porcine vitreous bodies, or hydrogels (alginate and polyethylene glycol (PEG)-based) was equilibrated with a balanced salt solution. Monitoring of bevacizumab in the aqueous phase was conducted for up to 24 h, and its effect on interfacial tension was studied. Significant differences in bevacizumab partitioning were observed across endotamponades after 24 h. In silicone oils, bevacizumab was found exclusively in the aqueous phase, while in the other endotamponades, it accumulated in the gel phase (96.1% in porcine vitreous body, 83.5% in alginate, and 27.6% in PEG-based hydrogel). Bevacizumab significantly reduced interfacial tension (40 to 8 mN/m), possibly enhancing silicone oil emulsification. The type of endotamponade heavily influenced the bevacizumab concentration in the aqueous. The vitreous body and replacement hydrogels likely serve as a drug reservoir, highlighting the need for in vivo studies to explore these interactions prior to clinical application.

Viscoelastic, Optical, and Surgical Properties of Vitreous Body Replacement Hydrogels After Aging Compared to Porcine Vitreous Bodies And Silicone Oils.

Purpose: First- (monomers), second- (pre-gelated), and third- (in situ gelating after injection) generation hydrogels were previously introduced to replace the vitreous body after vitrectomy surgery. In this study, we evaluated the surgical, optical, and viscoelastic properties of vitreous body replacement hydrogels before and after an accelerated aging protocol previously applied to intraocular implants. Methods: Measurements of injection force, removal speed using a clinically established vitrectomy setup, as well as evaluation of forward light scattering and viscoelastic properties before and after an accelerated aging protocol were conducted. Results were compared to porcine and human vitreous bodies, as well as currently clinically applied lighter- and heavier-than-water silicone oils. Results: Removal speed of all tested hydrogels is substantially lower than the removal speed of porcine vitreous body (0.2 g/min vs. 2.7 g/min for the best performing hydrogel and porcine vitreous body, respectively). Forward light scattering in second-generation vitreous body replacement hydrogels was higher after the aging process than the straylight of the average 70-year-old vitreous body (9.4 vs. 5.5 deg2/sr, respectively). The viscoelastic properties of all hydrogels did not change in a clinically meaningful manner; however, trends toward greater stiffness and greater elasticity after aging were apparent. Conclusions: This study demonstrates surgical weaknesses of the hydrogels that need to be addressed before clinical use, especially low removal speed. Pre-linked hydrogels (second-generation) showed inferior performance regarding surgical properties compared to in situ gelating hydrogels (third-generation). Translational Relevance: This study highlights possible pitfalls regarding surgical and optical properties when applying vitreous replacement hydrogels clinically.

Intravitreal Injections: Improving Sustainability by Reducing Clinical Waste. / Intravitreale Injektionen: Nachhaltigkeit durch Reduktion von Klinikabfall.

BACKGROUND: Intravitreal injections are one of the most commonly performed ophthalmic procedures. It is estimated that over 1 million intravitreal injections are performed in Germany annually. The aim of this study was to quantify the waste and carbon footprint associated with single-use injection sets, and to establish a waste reduction strategy. MATERIAL AND METHODS: The clinical waste and associated carbon footprint from standard disposable injection sets used by tertiary referral centres in Germany (n = 6) and the United Kingdom (n = 2) were assessed. The safety of performing intravitreal injections with a minimalistic material-sparing approach was evaluated. RESULTS: The average weight of an injection set (and hence the waste generated from each injection) was 165 g. On average, each injection set comprised 145 g (88%) of plastic, 2.1 g (1.3%) of metal, 4.3 g (2.6%) of paper, and 12.9 g (7.8%) of gauze/swabs. The production of such injection sets was extrapolated to a CO2 equivalent of 752.6 tonnes (t), and the incineration of the resulting waste to a CO2 equivalent of 301.7 t. For 1 million injections, this equates to 145.2 t of plastic, 2.1 t of metal, 4.3 t of paper, and 12.9 t of gauze/swabs. A material-sparing approach can reduce injection set-associated waste by 99% without necessarily compromising patient safety. CONCLUSION: A resource-saving approach to intravitreal injections can minimise the generation of clinical waste and its associated carbon footprint, thereby supporting sustainability.

Forward Light Scattering of the Vitreous Gel After Enzymatic Aging: An In Vitro Model to Study Vitreous Opacification.

Purpose: Symptomatic vitreous opacifications, so-called floaters, are difficult to objectively assess majorly limiting the possibility of in vitro studies. Forward light scattering was found previously to be increased in eyes with symptomatic floaters. Using an objective setup to measure forward light scattering, we studied the effects of enzymatically digesting the components of the vitreous body on straylight to develop an in vitro model of vitreous opacifications. Methods: Fifty-seven porcine vitreous bodies were digested using hyaluronidase, collagenase, trypsin, and bromelain, as well as using a combination of hyaluronidase + collagenase and hyaluronidase + bromelain. A modified C-Quant setup was used to objectively assess forward light scattering. Results: Depletion of hyaluronic acid majorly increased vitreous straylight (mean increase 34.4 deg2/sr; P = 0.01), whereas primarily digesting the vitreous gel with collagenase or trypsin did not significantly affect straylight. When collagenase or bromelain is applied in hyaluronic acid depleted vitreous gels, the increase in forward light scattering is reversed partially. Conclusions: The age-related loss of hyaluronic acid primarily drives the increase in vitreous gel straylight induced by conglomerates of collagen. This process can be reversed partially by digesting collagen. This in vitro model allows the objective quantification and statistical comparison of straylight burden caused by vitreous opacities and, thus, can serve as a first testing ground for pharmacological therapies, as demonstrated with bromelain.

Quantification of Straylight Induced by Silicone Oil Adherent to Intraocular Lenses of Different Materials.

PURPOSE: A complication of using silicone oil as an intraocular endotamponade is its adhesion to intraocular lenses (IOLs). Forward light scattering is a measure to quantify the optical disturbance caused by adherent oil droplets. We tested the straylight caused by silicone oil adhesion to different IOLs and examined whether an approved cleaning solution, F4H5, reverses the induced straylight. DESIGN: An experimental study. METHODS: Two hydrophobic acrylic IOL models and 1 hydrophilic model with a hydrophobic surface (n = 8 per model: 24 lenses) had straylight measured before contact with silicone oils, providing a baseline for subsequent testing: 12 lenses with lighter-than-water silicone oil (Siluron 2000) and 12 with heavier-than-water oil (Densiron 68). The final measurement was performed after cleansing with F4H5 when we used scanning electron and light microscopy to detect surface changes. RESULTS: Straylight was majorly increased in IOLs with adherent silicone oil (baseline vs adherent oil median 3.1 [2.1, 3.9] and 39.7 [22.7, 87.8] deg2/sr, respectively; P < .001). No difference was seen between heavier- and lighter-than-water silicone oils. Between IOL types, induced straylight varied significantly, with 1 hydrophobic model reaching the highest average straylight. F4H5 significantly reduced straylight values in all IOL types (median 9.4 [5.4, 13.8] deg2/sr). The microscopy revealed surface changes on the IOLs even after cleaning. CONCLUSIONS: Silicone oil adhesion to IOLs can induce amounts of straylight known to cause severe optical disturbance. F4H5 cleansing solution reversed straylight values to only slightly increased values. We found no difference in straylight formation between the lighter- and heavier-than-water silicone oils.

Forward Light Scattering of First to Third Generation Vitreous Body Replacement Hydrogels after Surgical Application Compared to Conventional Silicone Oils and Vitreous Body.

To treat certain vitreoretinal diseases, the vitreous body, a hydrogel composed of mostly collagen and hyaluronic acid, must be removed. After vitrectomy surgery, the vitreous cavity is filled with an endotamponade. Previously, pre-clinical hydrogel-based vitreous body substitutes either made from uncrosslinked monomers (1st generation), preformed crosslinked polymers (2nd generation), or in situ gelating polymers (3rd generation) have been developed. Forward light scattering is a measure of Stray light induced by optical media, when increased, causing visual disturbance and glare. During pinhole surgery, the hydrogels are injected into the vitreous cavity through a small 23G-cannula. The aim of this study was to assess if and to what extent forward light scattering is induced by vitreous body replacement hydrogels and if Stray light differs between different generations of vitreous body hydrogel replacements due to the different gelation mechanisms and fragmentation during injection. A modified C-Quant setup was used to objectively determine forward light scattering. In this study, we found that the 1st and 3rd generation vitreous body replacements show very low stray light levels even after injection (2.8 +/- 0.4 deg2/sr and 0.2 +/- 0.2 deg2/sr, respectively) as gel fragmentation and generation of interfaces is circumvented. The 2nd generation preformed hydrogels showed a permanent increase in stray light after injection that will most likely lead to symptoms such as glare when used in patients (11.9 +/- 0.9 deg2/sr). Stray light of the 2nd generation hydrogels was 3- and 2-fold increased compared to juvenile and aged vitreous bodies, respectively. In conclusion, this significant downside in the forward light scattering of the 2nd generation hydrogels should be kept in mind when developing vitreous body replacement strategies, as any source of stray light should be minimized in patients with retinal comorbidities.

New approaches to explanting high-viscosity silicone oil in retinal surgery-polyimide cannulas vs extraction sleeves vs a luer-trocar.

BACKGROUND: The removal of high-viscosity silicone oil in retinal surgery is time-intensive. In this laboratory and porcine eye study, we evaluated the efficiency of novel extraction techniques, namely shortened polyimide-cannulas, an extraction sleeve and an experimental luer-trocar system, for commercially available silicone oils. METHODS: The volume of silicone oil after a 5-min removal time was quantified. The feasibility of all studied techniques was additionally tested in vitrectomized porcine eyes. Siluron 1000, 2000, 5000 and Xtra, as well as Densiron 68 and Densiron Xtra were examined. RESULTS: Shortening the 23G-polyimide-cannula from 6 mm up to 1.5 mm led to a significantly higher mean aspirated volume (e.g., 1 ml/min to 1.7 ml/min for Siluron Xtra). The extraction sleeve and luer-trocar increased the flow threefold compared to the shortest polyimide cannulas at 23G (5.2 ml/min and 5.2 ml/min vs 1.7 ml/min for Siluron Xtra, respectively). The extraction sleeve and luer-trocar system reached a similar flow at 27G as the best performing 23G-cannula. Angulation and movement of the eye was possible with the 2 mm-cannula, no angulation was possible when using the extraction sleeve. Stability and control were not impaired with the experimental luer-trocar setup. CONCLUSION: Shorter polyimide-cannulas and extraction sleeves increase the extraction flow but may decrease stability during surgery. The luer-trocar system facilitates rapid removal while offering great stability and control. Small 27G silicone oil removal is possible and time efficient.

Capsule Dynamics, Implantation, and Explantation of the Smaller Incision, New-Generation Implantable Miniature Telescope: a Miyake-Apple Study.

PURPOSE: The smaller incision, new-generation implantable miniature telescope is a novel implant to optimize vision in retinal patients with central vision loss. Using Miyake-Apple techniques we visualized the device implantation, repositioning, and explantation, while noting capsular bag dynamics. METHODS: Using the Miyake-Apple technique, we assessed capsular bag deformation after successful implantation of the device in human autopsy eyes. We assessed rescue strategies for converting a sulcus implantation to a capsular implantation and explantation strategies. We noted the occurrence of posterior capsule striae, zonular stress, and the haptics' arc of contact with the capsular bag after implantation. RESULTS: Acceptable zonular stress was observed during the successful implantation of the SING IMT. When it was implanted in the sulcus, one could reposition the haptics into the bag with two spatulas using counter-pressure in an effective strategy despite inducing tolerable, medium zonular stress. A similar technique, in reverse, allows safe explantation without damaging the rhexis or the bag, while inducing similar medium, tolerable zonular stress. In all eyes we examined, the implant considerably stretches the bag, inducing a capsular bag deformation and posterior capsule striae. CONCLUSION: The SING IMT can be safely implanted without significant zonular stress. In sulcus implantation and explantation, repositioning of the haptic is achievable without perturbing zonular stress using the presented approaches. It stretches average-sized capsular bags to support its weight. This is achieved by an increased arc of contact of the haptics with the capsular equator.

Introducing Dynamic Stimulation Aberrometry: Binocular Objective Accommodation versus Subjective Measures.

Purpose: The objective measurement of binocular accommodation remains a challenge. The dynamic stimulation aberrometry (DSA) system uses wavefront measurements to dynamically assess accommodation. In this study, we sought to introduce this method in a large number of patients of varying age and compared it with the subjective push-up method as well as the historical results of Duane. Design: This study is an evaluation of diagnostic technology. Subjects: Ninety-one patients aged 20 to 67 years (70 healthy, phakic eyes and 21 myopic eyes after phakic intraocular lens implantation) were enrolled at a tertiary eye hospital. Methods: All patients underwent DSA measurements; the accommodative amplitude of 13 patients chosen at random was additionally examined using the subjective push-up method introduced by Duane. DSA measurements were also compared with Duane's historical results. Main Outcome Measures: Accommodative amplitude, dynamic parameters of accommodation, and near pupil motility. Results: Dynamic stimulation aberrometry allowed objective measurement of binocular accommodation, which decreased with age (e.g., 30-39 years vs. > 50 years; 3.8 ± 0.9 diopters [D] and 0.1 ± 0.4 D, respectively). Dynamic parameters, such as time delay of the commencement of accommodation after near target presentation, increased with age (0.26 ± 0.14 seconds for 20-30 years vs. 0.43 ± 0.15 seconds for 40-50 years, P = 0.0002). The objective accommodative amplitude was significantly smaller than Duane's historic results (P = 0.001) as well as the subjective push-up method. Dynamic stimulation aberrometry records pupil motility dynamically in parallel to wavefront measurements. Maximum pupil motility during accommodation significantly decreased with age (P = 0.0002). Maximum pupillary speed did not correlate significantly with age. Conclusions: Dynamic stimulation aberrometry allows objective, dynamic, binocular measurement of accommodation and pupil motility with high time resolution in subjects with accommodative amplitudes up to 7 D. This article introduces the method in a large study population and may serve as a control for further studies. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Effects of Ketamine Infusion on Breathing and Encephalography in Spontaneously Breathing ICU Patients.

BACKGROUND: Preclinical studies suggest that ketamine stimulates breathing. We investigated whether adding a ketamine infusion at low and high doses to propofol sedation improves inspiratory flow and enhances sedation in spontaneously breathing critically ill patients. METHODS: In this prospective interventional study, twelve intubated, spontaneously breathing patients received ketamine infusions at 5 mcg/kg/min, followed by 10 mcg/kg/min for 1 h each. Airway flow, pressure, and esophageal pressure were recorded during a spontaneous breathing trial (SBT) at baseline, and during the SBT conducted at the end of each ketamine infusion regimen. SBT consisted of one-minute breathing with zero end-expiratory pressure and no pressure support. Changes in inspiratory flow at the pre-specified time points were assessed as the primary outcome. Ketamine-induced change in beta-gamma electroencephalogram power was the key secondary endpoint. We also analyzed changes in other ventilatory parameters respiratory timing, and resistive and elastic inspiratory work of breathing. RESULTS: Ketamine infusion of 5 and 10 mcg/kg/min increased inspiratory flow (median, IQR) from 0.36 (0.29-0.46) L/s at baseline to 0.47 (0.32-0.57) L/s and 0.44 (0.33-0.58) L/s, respectively (p = .013). Resistive work of breathing decreased from 0.4 (0.1-0.6) J/l at baseline to 0.2 (0.1-0.3) J/l after ketamine 10 mcg/kg/min (p = .042), while elastic work of breathing remained unchanged. Electroencephalogram beta-gamma power (19-44 Hz) increased compared to baseline (p < .01). CONCLUSIONS: In intubated, spontaneously breathing patients receiving a constant rate of propofol, ketamine increased inspiratory flow, reduced inspiratory work of breathing, and was associated with an "activated" electroencephalographic pattern. These characteristics might facilitate weaning from mechanical ventilation.

Respiration and rapid eye movement (REM) sleep substructure: short versus long episodes.

Rapid eye movement (REM) sleep in rodents is defined by the presence of theta rhythm in the absence of movement. The amplitude and frequency of theta oscillations have been used to distinguish between tonic and phasic REM sleep. However, tonic REM sleep has not been further subdivided, although characteristics of network oscillations such as cross-frequency coupling between theta and gamma vary within this sub-state. Recently, it has been shown that theta-gamma coupling depends on an optimal breathing rate of ~5 Hz. The frequency of breathing varies strongly throughout REM sleep, and the duration of single REM sleep episodes ranges from several seconds to minutes, whereby short episodes predominate. Here we studied the relation between breathing frequency, accelerometer activity, and the length of REM sleep periods. We found that small movements detected with three-dimensional accelerometry positively correlate with breathing rate. Interestingly, breathing is slow in short REM sleep episodes, while faster respiration regimes exclusively occur after a certain delay in longer REM sleep episodes. Thus, merging REM sleep episodes of different lengths will result in a predominance of slow respiration due to the higher occurrence of short REM sleep periods. Moreover, our results reveal that not only do phasic REM sleep epochs predominantly occur during long REM sleep episodes, but that the long episodes also have faster theta and higher gamma activity. These observations suggest that REM sleep can be further divided from a physiological point of view depending on its duration. Higher levels of arousal during REM sleep, indicated by higher breathing rates, can only be captured in long REM sleep episodes.

Intravitreal Application: Physicochemical Properties of Drugs Dissolved in Silicone Oils of Different Density in Comparison to the Porcine Vitreous Body.

Silicone oil endotamponades provide a reservoir for drugs in the eye. Following vitrectomy surgery to treat retinal detachments, extensive diabetic retinopathy or endophthalmitis, they can be used as long-term lipophilic depots. This study aimed to investigate the physicochemical properties of intravitreally applied drugs of different lipophilicity, namely vancomycin, ceftazidime and voriconazole. For this purpose, an in vitro model of the silicone-oil-filled eye compared to porcine vitreous bodies (PVBs) was used. In a glass container, either light or heavy silicone oil or PVB was set into equilibrium with an aqueous fluid. Vancomycin, voriconazole and ceftazidime were added in concentrations commonly applied in clinical practice. The time course of the concentration of the drugs was determined in the hydrophilic phase for up to 24 h. With silicone oil present, the concentrations of vancomycin, voriconazole and ceftazidime were elevated in the aqueous humor when compared to the vitreous body (p < 0.001 for all drugs). With increasing lipophilicity, higher concentrations of the drug dissolved in silicone oil after 24 h (52.7%, 49.1% and 34.3% for vancomycin, ceftazidime and voriconazole, respectively). While no difference between lighter- and heavier-than-water silicone oil was apparent for vancomycin and ceftazidime (p = 0.17 and p = 0.72), voriconazole dissolved significantly better in the heavier-than-water silicone oil (p = 0.002). A higher-than-expected percentage of the glycopeptide vancomycin dissolved in the porcine vitreous body, possibly due to protein binding. In conclusion, silicone oils influence the drug concentration and distribution of intravitreally applied drugs depending on their lipophilicity. The addition of F6H8 used to create heavy silicone oils attenuates these effects for lipophilic drugs. Knowledge of the distribution of these intravitreally applied drugs is crucial to ensure the desired anti-infectious effect.

Physicochemical Properties of Explanted Silicone Oil After Use as an Intraocular Tamponade.

PURPOSE: We studied the effects of exposure to biological media within the eye, such as contamination with lipophilic and amphiphilic substances, on the physicochemical parameters of silicone oil used as an intraocular tamponade. METHODS: We removed silicone oil with visible emulsification from 15 patients and measured each sample for shear viscosity and surface tension. We induced in vitro emulsification with balanced salt solution. Using the zeta-potential, we evaluated the emulsion droplet's electrochemical stability. We repeated all experiments in a control group of unused oil. Electrochemical stability and viscosity were additionally measured in oils with high-molecular-weight components. RESULTS: We recovered silicone oils implanted between 30 and 506 days (mean, 196 days). Viscosity did not differ between explanted and control groups. Surface tension and zeta potential remained unchanged (P = 0.61 and P = 0.84, respectively). All oils showed a significant correlation of viscosity with temperature (P < 0.01 for all). Oils with added high-molecular-weight components showed a lower emulsion stability. CONCLUSIONS: Prolonged contact to hydrophilic biological media does not alter high-viscosity silicone oil's physicochemical parameters. During typical durations of intraocular use, lipophilic and amphiphilic molecules had no deleterious effect. The addition of high-molecular-weight components might decrease the silicone oil's electrochemical emulsion stability, possibly easing the confluence of emulsion droplets. TRANSLATIONAL RELEVANCE: Although the physicochemical parameters of silicone oils are not altered after clinically relevant durations within the eye, emulsion stability significantly differs between oil types.

THE NOVEL USE OF HIGH-FLOW POLYIMIDE CANNULAS TO IMPROVE SILICONE OIL INJECTABILITY IN VITREORETINAL SURGERY.

PURPOSE: The injection of high-viscosity silicone oil lengthens injection time. New polyimide cannulas offer a greater inner diameter than conventional metal cannulas at the same gauge. We compared the injection time for polyimide and metal cannulas at 23 G for a variety of silicone oils including a 12,500-mPas prototype oil. METHODS: In this laboratory study, injection time was measured three times per cannula and per oil. Warming the oil before injection to up to 42°C was also evaluated. Finally, the feasibility of polyimide cannulas was tested in vitrectomized porcine eyes. RESULTS: The 23-G polyimide cannula mostly decreased injection times. The time to inject 5 mL of Siluron Xtra and Siluron 5000 decreased by 6:02 (76.9%) minutes (483 vs. 121 seconds) and 12:01 (74.7%) minutes (973 vs. 252 seconds), respectively. Although the 23-G metal cannula failed to inject 12,500 mPas oil, 5 mL was injected in 10:21 minutes using the polyimide cannula. Prewarming Siluron 5000 to 42°C lowered the injection time by 9.0% and by 12.1% when using the metal or polyimide cannula, respectively. CONCLUSION: Polyimide cannulas allow a clinically relevant decrease in injection time. They may not only shorten surgery time but could also ease the use of next-generation ultra-high-viscosity silicone oils. Prewarming silicone oil leads to decreased injection times.

Competition law and pricing among biologic drugs: the case of VEGF therapy for retinal diseases.

Neovascular age-related macular degeneration (AMD) is a progressive eye disease and is a leading cause of vision loss in the Western world. Vascular endothelial growth factor inhibitors have become a mainstay of treatment for this disease. Currently, treatment options include three originator biologics with approvals for neovascular AMD (aflibercept, ranibizumab, and brolucizumab-dbll) and one biologic that is commonly used off-label for the condition (bevacizumab). In the USA, Medicare spending on these drugs consistently surpassed $4 billion per year between 2015 and 2019, driven by high prices and varying off-label use of bevacizumab, which is substantially cheaper than the other biologics used to treat neovascular AMD. In this article, we discuss how legal reform can improve market competition for biologic drugs, using AMD therapies as a case study. We chose this group of drugs for their significant contribution to Medicare spending, the price difference between approved therapies and intravitreal bevacizumab, and because there currently exists a large biosimilar pipeline with many drug candidates in the final stage of development. We propose mechanisms for anticipating and facilitating the market introduction of biosimilars, as well as changes to the pricing model in Medicare that can promote use of cost-effective therapies. Reforms such as empowering Medicare to negotiate drug prices may help ensure that introduction of new biologics and biosimilars for AMD will lower spending and increase patient access.

[Cataract surgery and the small eye: relative anterior microphthalmos, high hyperopia and nanophthalmos]. / Die Kataraktchirurgie und das kleine Auge: Relativer anteriorer Mikrophthalmus, hohe Hyperopie und Nanophthalmus.

Relative anterior microphthalmos, nanophthalmos and high-grade hyperopia are small eyes with different characteristic morphological relationships between the anterior segment and axis length. This article discusses the intraoperative challenges and surgical approaches to solutions for cataract operations in patients with one of the three named morphological alterations. Additionally, the article addresses possible comorbidities including glaucoma and preoperative planning.

Pupil dynamics after in-the-bag versus anterior and retropupillary iris-fixated intraocular lens implantation.

An Intraocular Lens (IOL) fixated on the iris either anteriorly, as a phakic IOL, or posteriorly, as an aphakic IOL, can influence pupil motility. In this interventional case series study, we evaluated pupil size under different levels of illumination (scotopic = 0.04 lx, low-mesopic = 0.4 lx and high-mesopic = 4 lx) for anterior iris-claw IOL fixation for correcting myopia or hyperopia (IFPH), retropupillary iris-claw IOL fixation to correct aphakia or as treatment for late in-the-bag IOL dislocation/subluxation (IFRP), and capsular-fixation IOL in-the-bag implantation (IB). Pupil size was measured preoperatively for the IFPH- and IB-group as well as 6 months after surgery for all groups. We analyzed a total of 70 eyes: 22 eyes of 11 patients with phakic IOLs, 22 eyes of 20 patients in the IFRP group and 26 eyes of 13 patients in the IB group. Both IFPH and IB showed a smaller postoperative scotopic pupil size, compared with the preoperative values. When compared to postoperative values of IB and IFPH, IFRP showed a significantly smaller postoperative scotopic pupil size (IFPH: 5.89 ± 0.83 mm, IFRP: 4.37 ± 0.83 mm, IB: 5.34 ± 0.98 mm, p < 0.001) while no differences were seen at high-mesopic lighting. Neither of the surgical techniques seems to impair the constriction of the pupil.