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.

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.

Optical Coherence Tomographic Optic Nerve Head Morphology in Myopia III: The Exposed Neural Canal Region in Healthy Eyes-Implications for High Myopia.

PURPOSE: To determine the prevalence and magnitude of optical coherence tomography (OCT) exposed neural canal (ENC), externally oblique choroidal border tissue (EOCBT), and exposed scleral flange (ESF) regions in 362 non-highly myopic (spherical equivalent -6.00 to 5.75 diopters) eyes of 362 healthy subjects. DESIGN: Cross-sectional study. METHODS: After OCT optic nerve head (ONH) imaging, Bruch membrane opening (BMO), the anterior scleral canal opening (ASCO), and the scleral flange opening (SFO) were manually segmented. BMO, ASCO, and SFO points were projected to the BMO reference plane. The direction and magnitude of BMO/ASCO offset as well as the magnitude of ENC, EOCBT, and ESF was calculated within 30° sectors relative to the foveal-BMO axis. Hi-ESF eyes demonstrated an ESF ≥100 µm in at least 1 sector. Sectoral peri-neural canal choroidal thickness (pNC-CT) was measured and correlations between the magnitude of sectoral ESF and proportional pNC-CT were assessed. RESULTS: Seventy-three Hi-ESF (20.2%) and 289 non-Hi-ESF eyes (79.8%) were identified. BMO/ASCO offset as well as ENC, EOCBT, and ESF prevalence and magnitude were greatest inferior temporally where the pNC-CT was thinnest. Among Hi-ESF eyes, the magnitude of each ENC region correlated with the BMO/ASCO offset magnitude, and the sectors with the longest ESF correlated with the sectors with proportionally thinnest pNC-CT. CONCLUSIONS: ONH BMO/ASCO offset, either as a cause or result of ONH neural canal remodeling, corresponds with the sectoral location of maximum ESF and minimum pNC-CT in non-highly myopic eyes. Longitudinal studies to characterize the development and clinical implications of ENC Hi-ESF regions in non-highly myopic and highly myopic eyes are indicated.

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.

Asymmetry of Peripapillary Retinal Blood Vessel and Retinal Nerve Fiber Layer Thickness Between Healthy Right and Left Eyes.

Purpose: The purpose of this study was to determine if there is asymmetry in retinal blood vessel (RBV) position and thickness between right and left eyes (R-L) and evaluate whether R-L asymmetry in RBV thickness is related to R-L asymmetry of retinal nerve fiber layer thickness (RNFLT). Methods: We analyzed peripapillary circle scan optical coherence tomography (OCT) examinations from healthy White subjects to measure RNFLT and RBV thickness and position relative to the fovea to Bruch's membrane opening axis, for all visible RBV. The R-L asymmetries of RNFLT and RBV thickness were computed for each A-scan. Four major vessels (superior temporal artery [STA] and superior temporal vein [STV], inferior temporal artery [ITA], and vein [ITV]) were identified using infrared images. Results: We included 219 individuals. The mean (standard deviation) number of RBV measured per eye was 15.0 (SD = 2.2). The position of the STV and STA was more superior in left eyes than in right eyes, by 2.4 degrees and 3.7 degrees, respectively (P < 0.01). There was no region with significant R-L asymmetry in RBV thickness. RNFLT was thicker in right eyes in the temporal superior region and thicker in left eyes in the superior and nasal superior regions, with the asymmetry profile resembling in a "W" shape. This shape was also present in post hoc analyses in two different populations. The R-L asymmetries of RBV and RNFLT at each A-scan were not significantly associated (P = 0.37). Conclusions: There is little R-L asymmetry in RBV, and it is not related to RNFLT asymmetry. This study suggests that R-L RNFLT asymmetry is due to factors other than RBV.

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.

Peripapillary Scleral Bowing Increases with Age and Is Inversely Associated with Peripapillary Choroidal Thickness in Healthy Eyes.

PURPOSE: To use optical coherence tomography (OCT) to 3-dimensionally characterize the optic nerve head (ONH) in peripapillary scleral bowing in non-highly myopic healthy eyes. DESIGN: Cross-sectional, multicenter study. METHODS: A total of 362 non-highly myopic (+6 diopters [D] > spherical equivalent > -6D) eyes of 362 healthy subjects from 20-90 years old underwent OCT ONH radial B-scan imaging. Bruch's membrane (BM), BM opening (BMO), anterior scleral canal opening (ASCO), and the peripapillary scleral surface were segmented. BMO and ASCO planes were fit, and their centroids, major axes, ovality, areas and offsets were determined. Peripapillary scleral bowing was characterized by 2 parameters: peripapillary scleral slope (ppSS) of 3 anterior peripapillary scleral segments (0-300, 300-700, and 700-1,000 µm from the ASCO centroid); and ASCO depth relative to a peripapillary scleral reference plane (ASCOD-ppScleral). Peripapillary choroidal thickness (ppCT) was calculated relative to the ASCO as the minimum distance between the anterior scleral surface and BM. RESULTS: Both ppSS and ASCOD-ppScleral ranged from slightly inward through profoundly outward in direction. Both parameters increased with age and were independently associated with decreased ppCT. CONCLUSIONS: In non-highly myopic healthy eyes, outward peripapillary scleral bowing achieved substantial levels, was markedly increased with age, and was independently associated with decreased peripapillary choroidal thickness. These findings provide a normative foundation for characterizing this anatomy in cases of high myopia and glaucoma and in eyes with optic disc tilt, torsion, and peripapillary atrophy.

Differential Effects of Aging in the Macular Retinal Layers, Neuroretinal Rim, and Peripapillary Retinal Nerve Fiber Layer.

PURPOSE: We determined the differential aging effects of the inner 6 layers of the macula in contrast to the minimum neuroretinal rim width (MRW) and peripapillary retinal nerve fiber layer (RNFL) thickness. DESIGN: Cross-sectional, multicenter study. PARTICIPANTS: An approximately equal number of white subjects with a normal ocular and visual field examination in each decade group from 20 to 90 years. METHODS: OCT of the macula, optic nerve head, and peripapillary retina. MAIN OUTCOME MEASURES: Sectoral measurements of the inner 6 layers of the macula; age-related decline of each of these layers; strength of the associations with age of the macular parameters, MRW, and peripapillary RNFL thickness; and association between ganglion cell layer (GCL) thickness and MRW and peripapillary RNFL thickness. RESULTS: The study sample comprised 1 eye of 246 subjects with a median (range) age of 52.9 (19.8-87.3) years. Of the 6 layers, there was a statistically significant decline with age of only the GCL, inner plexiform layer, and inner nuclear layer thickness with rates of -0.11 µm/year, -0.07 µm/year, and -0.03 µm/year, respectively. These rates corresponded to 2.82%, 2.10%, and 0.78% loss per decade, respectively, and were generally uniform across sectors. The rate of loss of MRW and peripapillary RNFL thickness was -1.22 µm/year and -0.20 µm/year, corresponding to 3.75% and 2.03% loss per decade. However, the association of GCL thickness change with age (R2 = 0.28) was approximately twice that of MRW and RNFL thickness (R2 = 0.14 for each). CONCLUSIONS: In concordance with histopathologic studies showing age-related loss of retinal ganglion cell axons, we showed a significant decline in GCL thickness, as well as MRW and peripapillary RNFL thickness. The stronger relationship between aging and GCL thickness compared with the rim or peripapillary RNFL may indicate that GCL thickness could be better suited to measure progression of structural glaucomatous loss.

OCT-Detected Optic Nerve Head Neural Canal Direction, Obliqueness, and Minimum Cross-Sectional Area in Healthy Eyes.

PURPOSE: To assess anterior scleral canal opening (ASCO) offset relative to Bruch's membrane opening (BMO) (ASCO/BMO offset) so as to determine neural canal direction, obliqueness, and minimum cross-sectional area (NCMCA) in 362 healthy eyes. DESIGN: Cross-sectional study. METHODS: After optical coherence tomography optic nerve head and retinal nerve fiber layer thickness (RNFLT) imaging, BMO and ASCO were manually segmented. Planes, centroids, size, and shape were calculated. Neural canal direction was defined by projecting the neural canal axis vector (connecting BMO and ASCO centroids) onto the BMO plane. Neural canal obliqueness was defined by the angle between the neural canal axis and the BMO plane perpendicular vector. NCMCA was defined by projecting BMO and ASCO points onto a neural canal axis perpendicular plane and measuring the area of overlap. The angular distance between superior and inferior peak RNFLT was measured, and correlations between RFNLT, BMO, ASCO, ASCO/BMO offset, and NCMCA were assessed. RESULTS: Mean (SD) NCMCA was significantly smaller than either the BMO or ASCO area (1.33 (0.42), 1.82 (0.38), 2.22 (0.43) mm2, respectively), and most closely correlated to RNFLT (P < .001, R2 = 0.158). Neural canal direction was most commonly superior-nasal (55%). Mean neural canal obliqueness was 39.4° (17.3°). The angular distance between superior and inferior peak RNFLT correlated to neural canal direction (P ≤ .008, R2 = 0.093). CONCLUSIONS: ASCO/BMO offset underlies neural canal direction, obliqueness, and NCMCA. RNFLT is more strongly correlated to NCMCA than to BMO or ASCO, and its peripapillary distribution is influenced by neural canal direction.

Factors Influencing Optical Coherence Tomography Peripapillary Choroidal Thickness: A Multicenter Study.

Purpose: To quantify peripapillary choroidal thickness (PCT) and the factors that influence it in healthy participants who represent the racial and ethnic composition of the U.S. population. Methods: A total of 362 healthy participants underwent optical coherence tomography (OCT) enhanced depth imaging of the optic nerve head with a 24 radial B-scan pattern aligned to the fovea to Bruch's membrane opening axis. Bruch's membrane, anterior scleral canal opening (ASCO), and the anterior scleral surface were manually segmented. PCT was measured at 100, 300, 500, 700, 900, and 1100 µm from the ASCO globally and within 12 clock-hour sectors. The effects of age, axial length, intraocular pressure, ethnicity, sex, sector, and ASCO area on PCT were assessed by ANOVA and univariable and multivariable regressions. Results: Globally, PCT was thicker further from the ASCO border and thinner with older age, longer axial length, larger ASCO area, European descent, and female sex. Among these effectors, age and axial length explained the greatest proportion of variance. The rate of age-related decline increased further from the ASCO border. Sectorally, the inferior-temporal sectors were thinnest (10.7%-20.0% thinner than the thickest sector) and demonstrated a higher rate of age-related loss (from 15.6% to 20.7% faster) at each ASCO distance. Conclusions: In healthy eyes, PCT was thinnest in the inferior temporal sectors and thinner PCT was associated with older age, European descent, longer axial length, larger ASCO area, and female sex. Among these associations, age had the strongest influence, and its effect was greatest within the inferior temporal sectors.

Injectable 0.19-mg fluocinolone acetonide intravitreal implant for the treatment of non-infectious uveitic macular edema.

BACKGROUND: A retrospective observational clinical study to evaluate the safety and effectiveness of the injectable 0.19-mg fluocinolone acetonide intravitreal implant (ILUVIEN) in the treatment of non-infectious uveitic macular edema. RESULTS: Data are presented from eight patients (11 eyes) with non-infectious uveitic macular edema who were treated with a 0.19-mg fluocinolone acetonide implant. Nine out of 11 eyes were pseudophakic prior to implantation of fluocinolone acetonide implant, and both phakic eyes required cataract surgery during the follow-up period (the median follow-up was 19 months; range, 8-42 months). Effectiveness and safety were assessed from changes in central retinal thickness (measured using spectral domain optical coherence tomography), corrected distance visual acuity, uveitic activity, and intraocular pressure. The main outcome measures were changes in central retinal thickness, corrected distance visual acuity, uveitic activity, and intraocular pressure. In 11/11 eyes, central retinal thickness improved between months 1 and 3. The mean maximum decrease of central retinal thickness throughout the follow-up period was 168 ± 202 µm (± standard deviation). Nine out of 11 eyes showed an improvement in corrected distance visual acuity (between + 1 and + 8 lines), and 2/11 eyes lost corrected distance visual acuity (- 1 and - 3 lines, respectively). Nine out of 11 eyes presented with inactive inflammation during the follow-up period, and in 1/11 eyes, there was a relapse at month 42. Four out of 11 eyes presented with a relapse of macular edema between months 3 and 8. The mean increase in intraocular pressure was 2.1 ± 4.7 mmHg. Nine eyes were pseudophakic prior to implantation of the injectable fluocinolone acetonide intravitreal implant. Both phakic patients developed a cataract that was treated with cataract surgery in the follow-up period. CONCLUSIONS: In this small case series with long-term follow-up, treatment of non-infectious uveitic macular edema with the injectable fluocinolone acetonide implant was associated with improved central retinal thickness and corrected distance visual acuity and a manageable safety profile. The advantage of this device is the long-term drug release and the fact that it can be injected into the vitreous as a minor surgical procedure, which is in contrast to other treatment options.

Protruded retinal layers within the optic nerve head neuroretinal rim.

PURPOSE: To determine the frequency with which retinal tissues other than the nerve fibre layer, hereafter referred to as protruded retinal layers (PRL), are a component of optical coherence tomography (OCT) neuroretinal rim measurements. METHODS: Ninety healthy (30 White, Black and Japanese, respectively) subjects were included in the study. A radial scan pattern (24 B-scans centred on Bruch's membrane opening [BMO]) was used. For each of the 48 minimum rim width (MRW) measurement points, we determined whether PRL were present, absent or indeterminate. When present, the proportion of PRL within the MRW was quantified. RESULTS: Protruded retinal layers were present in 503 (11.6%), absent in 3805 (88.1%) and indeterminate in 12 (0.3%) measurement points. Overall, 69 (76.6%) subjects had ≥1 points with PRL, with White subjects having the highest frequency and Japanese the lowest (29 [97%] and 18 [60%], respectively; p < 0.01). PRL were present in one-third of points in the temporal sector, but ≤5% in other sectors. When present, the median PRL thickness was 53.0 (interquartile range [IQR]: 33.0 to 78.5) µm, representing 20.6 (IQR: 13.0 to 28.5)% of MRW. Globally, the median PRL thickness comprised 1.3 (IQR: 0.2 to 3.5)% of the MRW; however, in the temporal sector, it exceeded 30% of MRW in some subjects. CONCLUSIONS: Protruded retinal layers are a component of MRW measurements in most normal subjects, occurring in almost 12% of all measurement points analysed. There were racial variations in the presence of PRL and a significantly higher frequency of PRL in the temporal sector.

Factors Influencing Central Lamina Cribrosa Depth: A Multicenter Study.

Purpose: To quantify the influence of ocular and demographic factors on central laminar depth (LD) in healthy participants. Methods: A total of 362 normal subjects underwent optical coherence tomography (OCT) enhanced depth imaging of the optic nerve head (ONH) with a 24 radial B-scan pattern aligned to the fovea-to-Bruch's membrane opening (BMO) axis. BMO, anterior lamina, anterior scleral canal opening (ASCO), Bruch's membrane (BM), and the peripapillary scleral surface were manually segmented. The extent of laminar segmentation was quantified within 72 ASCO subsectors. Central LD was quantified relative to four reference planes: BMO, ASCO, BM, and scleral. The effects of age, sex, ethnicity, IOP, BMO area, ASCO area, and axial length on LD were assessed. Results: Laminar visibility was most consistent within the central ASCO (median 89%, range, 69%-95%). LDBMO and LDBM were significantly shallower in eyes with greater age, BMO area, and axial length and in females. LDASCO was shallower in eyes with greater ASCO area and axial length and in European and Hispanic descent compared to African descent eyes. LDSclera behaved similarly, but was not associated with axial length. BMO and ASCO area were not different between African descent and European descent eyes. Conclusions: Central LD was deeper in African descent eyes and influenced least by age, axial length, and sex, but more by ASCO area, when measured relative to the ASCO and sclera. However, the magnitude of these effects for all four reference planes was small, and their clinical importance in the detection of glaucoma and its progression remains to be determined.

Optical and material analysis of opacified hydrophilic intraocular lenses after explantation: a laboratory study.

BACKGROUND: The opacification of hydrophilic intraocular lenses (IOLs) is a very rare complication in terms of absolute numbers. We report on the analyses of opacified Euromaxx ALI313Y and ALI313 IOLs (Argonoptics, Germany) using light and scanning electron microscopy, X-ray spectroscopy and optical bench analysis. METHODS: Opacified Euromaxx ALI313Y and ALI313 IOLs were explanted after patients presented with a decrease in visual acuity. The explants were sent to our laboratory and examined using light and scanning electron microscopy. The composition of the deposits was analysed using X-ray spectroscopy. The optical quality of the intraocular lens (IOL) was assessed using the OptiSpheric IOL PRO optical bench (Trioptics GmbH Wedel, Germany). Modulation transfer function (MTF) was measured at all spatial frequencies and United States Air Force (USAF) 1951 resolution target pictures were documented. RESULTS: Macroscopically, the entire optic was opacified in all IOLs. Light and scanning electron microscopy revealed numerous fine, granular, crystalline-like deposits, which were always distributed in a line parallel to the anterior and posterior surfaces of the IOLs. X-ray spectroscopy could prove the deposits consisted of Calcium and Phosphate. Measurements in the optical bench showed deterioration of MTF values at all spatial frequencies and the USAF target pictures demonstrated a significant reduction of brightness as well as resolution with the opacified IOLs. CONCLUSIONS: The calcification of hydrophilic IOLs only occurs rarely. The exact chemical composition of the deposits can be assessed by means of X-ray spectroscopy. Optical quality analysis of the explanted Euromaxx ALI313Y and ALI313 IOLs showed significant reduction of MTF values, which was confirmed by USAF target pictures.

Intraocular Pharmacokinetics of Aflibercept and Vascular Endothelial Growth Factor-A.

PURPOSE: To determine intraocular pharmacokinetics of aflibercept and VEGF-A in patients with neovascular age-related macular degeneration (nAMD) during a treatment period of 6 months. METHODS: Seven nonvitrectomized patients diagnosed with macular edema secondary to nAMD undergoing intravitreal injections (IVI) of aflibercept. Patients were treatment naïve at least for the last 2 months and received intravitreal injection of 2 mg aflibercept for the first time. Aqueous humor samples were obtained prior to each injection procedure during a 6-month period: three times monthly, then bimonthly. Over all 35 samples were analyzed with ELISA for unbound VEGF-A and a self-developed assay for unbound aflibercept. RESULTS: In all cases, wet AMD was inactive after IVI. Unbound aflibercept could be detected in all samples. Initial mean concentration of aflibercept was 305.4 ± 43.8 µg/mL and remained stable after the first injection with 0.8 ± 0.5 µg/mL. Initial mean level of unbound VEGF-A was 190.7 ± 26.9 pg/mL. A significant decrease of the concentration to 92.6 ± 10.2 pg/mL (P < 0.05, Wilcoxon rank sum test) after the first injection was observed. This level remained stable during further treatment. CONCLUSIONS: Levels of unbound aflibercept and unbound VEGF-A remained stable after every month and every second month of IVI. The findings of these small case series support suggestions that treatment intervals with bimonthly IVI of aflibercept are sufficient due to a detectable remaining biologic active concentration of aflibercept.