Effects of graft detachment on the central corneal thickness after uncomplicated Descemet membrane endothelial keratoplasty.

PURPOSE: To determine if early central corneal thickness (CCT) and best-corrected visual acuity (BCVA) changes indicate graft detachment after uncomplicated Descemet membrane endothelial keratoplasty (DMEK). METHODS: In this analysis of our prospectively collected ADDA registry data ( https://drks.de/search/de/trial/DRKS00027180 ), 45 pseudophakic eyes underwent DMEK surgery at the Department of Ophthalmology, RWTH Aachen University. Anterior segment optical coherence tomography (AS-OCT), the presence of stromal ripples on the posterior corneal surface, and BCVA measurements were assessed prior to, 1 day, 1 week, 1 month, and 6 months after surgery. RESULTS: Eyes were categorized into three groups: no graft detachment (group 1) (20/45; 44.4%), < 1/3 graft detachment (group 2) (14/45; 31.1%), ≥ 1/3 graft detachment followed by rebubbling (group 3) (11/45; 24.4%). Eyes in group 3 had a greater CCT prior to (746.8 ± 95.8 µm vs. 665.0 ± 74.4 µm, P = 0.041), and 1 week (666.8 ± 119.5 µm vs. 556.5 ± 56.8 µm, P = 0.001) after DMEK compared to group 1. By 1 month, CCT in all groups aligned. Comparing prior to and 1 week after DMEK, none of the eyes in group 1 had an increase in CCT, while the CCT increased in 25.0% of eyes in group 2 and 22.2% in group 3. In group 1, 90.0% had a CCT of < 600 µm 1 week after DMEK, compared to only 50.0% in group 2 and 36.4% in group 3. In group 1, 90.0% (18/20) had an improved BCVA 1 week after DMEK, while in groups 2 and 3, 86.7% (12/14) and 18.2% (2/11) improved, respectively. One patient in group 3 showed posterior stromal ripples 1 day and 1 week after DMEK. CONCLUSION: If 1 week after uncomplicated DMEK CCT is < 600 µm and has decreased from before surgery, BCVA has improved, and there are no posterior stromal ripples, a graft detachment ≥ 1/3 and the need for rebubbling are very unlikely. In all other cases, meticulous slit-lamp and OCT inspection of the peripheral graft for detachments should be advised.

Clinical Landscape of Central Serous Chorioretinopathy in Germany: Retina.net CSC Registry Report Number 1.

INTRODUCTION: The German Registry of central serous chorioretinopathy (CSC) collects data on CSC patients in a nationwide multicenter approach to analyze epidemiology, risk factors, clinical presentations, as well as diagnosis and treatment patterns. METHODS: In this multicenter cohort study, patients with CSC were enrolled in nine tertiary referral centers in Germany between January 2022 and June 2023. After consenting to the study, demographic data, risk factors, reported symptoms, best-corrected visual acuity (BCVA), funduscopic findings, disease severity, and diagnostic and treatment decisions were recorded and analyzed. RESULTS: A total of 539 eyes of 411 CSC patients were enrolled in this study including 308 males (75%) and 103 females (25%). Patients were predominantly of Caucasian origin and had a mean age of 55.5 years (IQR 41.0-70.0). 28% of eyes were classified as acute (<4 months duration) CSC, 28% as chronic (>4 months duration) CSC, 21% as inactive CSC, 11% as chronic atrophic CSC, and 12% as CSC with secondary CNV. 128 patients (31%) demonstrated bilateral CSC. The most common risk factors reported were psychological stress (52%), smoking (38%), arterial hypertension (38%), and a history of or current use of steroids (30%). Most frequently encountered symptoms included decreased visual acuity (76%), metamorphopsia (49%), relative scotoma (47%), blurred vision (19%), and dyschromatopsia (9%). The mean logMAR BCVA on initial examination was 0.2 (≈20/30, IQR 0.2-0.4) but showed significant variation with a tendency of lower BCVA in chronic cases. At the baseline visit, 74% of the overall cohort received no treatment, while 19% underwent local treatment and only 2% underwent systemic treatment. Of the local therapies, anti-VEGF injections were the most frequently performed procedure (33%, mainly for secondary CNV), followed by micropulse laser (28%), focal nonpulsed laser (23%), verteporfin photodynamic therapy (14%), and nonsteroidal anti-inflammatory eye drops (2%). Among intravitreal anti-VEGF agents, aflibercept was used most frequently, followed by bevacizumab and ranibizumab. CONCLUSION: This registry represents one of the largest cohorts of European patients with CSC to date. Patient age and the proportion of women were higher than expected and bilateral active disease was lower than anticipated, highlighting that neither age nor gender should be overemphasized when diagnosing CSC. Therapeutic interventions are heterogeneous and include verteporfin photodynamic therapy, micropulse laser, and anti-VEGF injections in case of secondary CNV.

Fullfield and extrafoveal visual evoked potentials in healthy eyes: reference data for a curved OLED display.

PURPOSE: Visual evoked potentials (VEP) present an important diagnostic tool in various ophthalmologic and neurologic diseases. Quantitative response data varied among patients but are also dependent on the recording and stimulating equipment. We established VEP reference values for our setting which was recently modified by using a curved OLED display as visual stimulator. Distinction is made between fullfield (FF) and extrafoveal (EF) conduction, and the effect of sex, age and lens status was determined. METHODS: This prospective cross-sectional study included 162 healthy eyes of 162 test persons older than 10 years. A fullfield pattern-reversal visual evoked potential (FF-PR-VEP) with two stimulus sizes (ss) (20.4' and 1.4°) as well as an extrafoveal pattern onset-offset VEP (EF-P-ON/OFF-VEP) (ss 1.4° and 2.8°) was derived in accordance with the International Society for Clinical Electrophysiology of Vision guidelines. Amplitudes and latencies were recorded, and the mean values as well as standard deviations were calculated. Age- and sex-dependent influences and the difference between phakic and pseudophakic eyes were examined. A subanalysis of EF-P-ON/OFF-VEP and fullfield pattern onset-offset VEP (FF-P-ON/OFF-VEP) was performed. A 55-inch curved OLED display (LG55EC930V, LG Electronics Inc., Seoul, South Korea) was used as visual stimulator. RESULTS: Mean P100 latency of the FF-PR-VEP was 103.81 ± 7.77 ms (ss 20.4') and 102.58 ± 7.26 ms (ss 1.4°), and mean C2 latency of the EF-P-ON/OFF-VEP was 102.95 ± 11.84 ms (ss 1.4°) and 113.58 ± 9.87 ms (ss 2.8°). For all stimulation settings (FF-PR-VEP, EF-P-ON/OFF-VEP), a significant effect of age with longer latencies and smaller amplitudes in older subjects and higher amplitudes in women was observed. We saw no significant difference in latency or amplitude between phakic and pseudophakic eyes and between EF-P-ON/OFF-VEP and FF-P-ON/OFF-VEP. CONCLUSIONS: A curved OLED visual stimulator is well suited to obtain VEP response curves with a reasonable interindividual variability. We found significant effects of age and gender in our responses but no effect of the lens status. EF-P-ON/OFF-VEP tends to show smaller amplitudes.

TREATMENT OF PERSISTENT MACULAR HOLES WITH HEAVY SILICONE OIL.

BACKGROUND/PURPOSE: To determine anatomical success and best-corrected visual acuity after secondary surgery with heavy silicone oil tamponade in patients with persistent full-thickness macular holes. METHODS: In this retrospective study, 63 eyes with persistent full-thickness macular holes after primary pars plana vitrectomy and internal limiting membrane peeling underwent secondary surgery with heavy silicone oil tamponade. Macular spectral domain optical coherence tomography and best-corrected visual acuity measurements were performed during the follow-up. RESULTS: Fifty of 63 eyes (79.4%) achieved anatomical success. In eyes achieving anatomical success, best-corrected visual acuity before primary vitreoretinal surgery was significantly better (0.77 [∼20/125 Snellen] ± 0.24 [1.3-0.3] logarithm of the minimum angle of resolution) compared with eyes not achieving anatomical success (0.88 [∼20/160 Snellen] ± 0.17 [1.1-0.6] logarithm of the minimum angle of resolution, P = 0.044). Minimum linear diameter of full-thickness macular holes was significantly smaller in eyes achieving anatomical success, both before primary (403.4 ± 128.7 [199.0-707.0] µ m vs. 568.1 ± 209.1 [307.0-953.0] µ m, P = 0.009) and secondary surgery (464.1 ± 215.0 [178.0-1,521.0] µ m vs. 663.3 ± 228.5 [451.0-1,301.0] µ m, P = 0.010). Patients remaining phakic during all three surgeries did not benefit from best-corrected visual acuity improvement, although anatomical success was achieved. CONCLUSION: Heavy silicone oil tamponade in secondary surgery for persistent full-thickness macular holes is a safe and efficient surgical method. Best-corrected visual acuity and minimum linear diameter before surgery may be indicators for anatomical success.

Outcomes of combined single-use dual blade goniotomy and cataract surgery.

PURPOSE: Single-use dual blade goniotomy (SBG) is a novel ab interno procedure that removes three to five clock hours of trabecular meshwork (TM). We analysed the reduction of intraocular pressure (IOP) and topical glaucoma medication (Meds) in eyes following combined cataract surgery and SBG (Cat-SBG). METHODS: IOP and Meds were evaluated retrospectively in 55 eyes of 38 patients. 44 eyes had high tension glaucoma (HTG) and eleven eyes had normal tension glaucoma (NTG). Complete success (no Meds) and qualified success (with Meds) for IOP levels ≤ 21, ≤ 18 , ≤ 16 mmHg or ≥ 20% IOP reduction at the two- and six-month follow-up were evaluated. RESULTS: IOP and Meds were significantly reduced from before to two months after Cat-SBG in HTG- and NTG-patients (HTG: IOP 19.4 ± 3.3 to 15.1 ± 3.3 mmHg; p < 0.001; Meds 2.1 ± 1.3 to 0.8 ± 1.3; p < 0.001; NTG: IOP 14.0 ± 2.3 to 11.5 ± 2.3 mmHg; p = 0.004; Meds 1.6 ± 0.7 to 0.3 ± 0.7; p < 0.001). IOP and Meds did not change significantly from two to six months after Cat-SBG. In HTG, complete and qualified success rates were 43% (19/44) and 93% (41/44) for IOP ≤ 18 mmHg, 36% (16/44) and 64% (28/44) for IOP ≤ 16 mmHg and 30% (13/44) and 43% (19/44) for ≥ 20% IOP reduction six months after surgery. In NTG, complete and qualified success was 81% (9/11) and 100% (11/11) for IOP ≤ 18 and ≤ 16 mmHg, and 27% (3/11) for IOP reduction ≥ 20%. IOP and Meds reduction were comparable between HTG and NTG eyes. Only minor postoperative complications occurred. CONCLUSION: Cat-SBG is an efficient method to significantly lower IOP in patients with HTG and NTG.

New epiretinal implant with integrated sensor chips for optical capturing shows a good biocompatibility profile in vitro and in vivo.

BACKGROUND: Retinal degenerative diseases, e.g., retinitis pigmentosa, cause a severe decline of the visual function up to blindness. Treatment still remains difficult; however, implantation of retinal prostheses can help restoring vision. In this study, the biocompatibility and surgical feasibility of a newly developed epiretinal stimulator (OPTO-EPIRET) was investigated. The previously developed implant was extended by an integrated circuit-based optical capturing, which will enable the immediate conversion of the visual field into stimulation patterns to stimulate retinal ganglion cells. RESULTS: The biocompatibility of the OPTO-EPIRET was investigated in vitro using the two different cell lines L-929 and R28. Direct and indirect contact were analyzed in terms of cell proliferation, cell viability, and gene expression. The surgical feasibility was initially tested by implanting the OPTO-EPIRET in cadaveric rabbit eyes. Afterwards, inactive devices were implanted in six rabbits for feasibility and biocompatibility testings in vivo. In follow-up controls (1-12 weeks post-surgery), the eyes were examined using fundoscopy and optical coherence tomography. After finalization, histological examination was performed to analyze the retinal structure. Regarding the in vitro biocompatibility, no significant influence on cell viability was detected (L929: < 1.3% dead cells; R-28: < 0.8% dead cells). The surgery, which comprised phacoemulsification, vitrectomy, and implantation of the OPTO-EPIRET through a 9-10 mm corneal incision, was successfully established. The implant was fixated with a retinal tack. Vitreal hemorrhage or retinal tearing occurred as main adverse effects. Transitional corneal edema caused difficulties in post-surgical imaging. CONCLUSIONS: The OPTO-EPIRET stimulator showed a good biocompatibility profile in vitro. Furthermore, the implantation surgery was shown to be feasible. However, further design optimization steps are necessary to avoid intra- and postoperative complications. Overall, the OPTO-EPIRET will allow for a wide visual field and good visual acuity due to a high density of electrodes in the central retina.

Effects of uncomplicated Descemet membrane endothelial keratoplasty on the central retinal thickness.

PURPOSE: To determine retinal thickness (RT) changes and the incidence of macular edema after uncomplicated Descemet membrane endothelial keratoplasty (DMEK-ME) in patients without ME risk factors. METHODS: In this retrospective study, 107 pseudophakic eyes of 74 patients with Fuchs endothelial dystrophy (FED) (79.4%) or bullous keratopathy (BK) (20.6%) underwent DMEK surgery between 2016 and 2019 at the Department of Ophthalmology, RWTH Aachen University. Patients with intra- or postoperative complications as well as pre-existing risk factors for ME were excluded. Macular spectral-domain optical coherence tomography (SD-OCT) and best spectacle-corrected visual acuity (BSCVA) measurements were performed before, 1 week, 1 month, and 6 months after surgery. Retinal thickness (RT) was analyzed in the central foveal 1 mm (CSF), parafoveal 3 mm and 6 mm subfield. RESULTS: Eight eyes (7.5%) developed DMEK-ME 1 month after surgery. Six DMEK-ME eyes (75%) were rebubbled, compared with 31.3% (31 of 99; P = 0.02) of the non DMEK-ME eyes. DMEK-ME eyes had a significantly thicker CSF 1 month after surgery (432.0 ± 97.6 µm) compared with non-DMEK-ME eyes (283.7 ± 22.2 µm; P = 0.01). The other subfields and time points showed no significant RT changes. DMEK-ME significantly impaired BSCVA (0.38 ± 0.92 logMAR) only 1 month after surgery in comparison to the non DMEK-ME eyes (0.23 ± 0.87 logMAR, P = 0.015). CONCLUSION: Excluding systemic and surgery-related risk factors, rebubbling increases the risk of DMEK-ME. Performing a CSF scan 1 month after surgery, particularly in rebubbled eyes, efficiently detects DMEK-ME and allows the prompt initiation of treatment, e.g., topical corticosteroid and non-steroidal (NSAID) eye drops.

Outcomes of 360° suture trabeculotomy after unsuccessful canaloplasty.

BACKGROUND: Canaloplasty is a well-established non-penetrating glaucoma surgery. Unsuccessful outcomes can be enhanced by micro-invasive 360° suture trabeculotomy (360°trabeculotomy), analyzed in this study. METHODS: This retrospective study included twenty eyes of 19 patients, mean age 59.7±17.2 years, with primary open-angle glaucoma (POWG n = 14), pseudoexfoliation glaucoma (PEX n = 3), juvenile glaucoma (n = 2) and aphakic glaucoma (n = 1), who underwent micro-invasive 360° trabeculotomy after unsuccessful (intraocular pressure (IOP) >21 mmHg under maximum glaucoma eye drop therapy (Meds)) canaloplasty. IOPs, Meds, complications and failure rates (IOP >21 mmHg at two consecutive follow-ups) were evaluated. Complete success (no Meds) and qualified success (with Meds) rates for IOP levels ≤21 mmHg and ≤ 18 mmHg at the last follow-up were evaluated. RESULTS: IOPs and Meds were significantly reduced from before to 1 week (10.3±3.1 days) after 360° trabeculotomy (IOP, 28.3±6.0 mmHg to 15.8±4.5 mmHg; p < 0.001; Meds, 3.1 ± 1.2 to 1.0 ± 1.2; p < 0.001). IOPs (p = 0.37) and Meds (p = 0.33) did not decrease further from 1 week until the last follow-up (18.3 ± 8.2 months (IOP, 14.4±3.8 mmHg; Meds, 1.5±1.3)). Complete and qualified success was 25% (5/20) and 70% (14/20) for IOP ≤21 mmHg, as well as 25% (5/20) and 60% (12/20) for IOP ≤18 mmHg. Four eyes had postoperative hyphema, which resolved after a mean period of 4.0 ± 2.2 days. Five failures occurred after a mean of 40.6 ± 51.9 days after 360° trabeculotomy. All failures underwent trabeculectomy. Eyes that needed early (≤3 months post canaloplasty) 360° trabeculotomy showed higher IOPs before (p < 0.001) and lower (p = 0.03) IOPs 2 months post 360° trabeculotomy than eyes with late (>3 months) 360° trabeculotomy surgery. CONCLUSIONS: 360° trabeculotomy is a safe, micro-invasive, simple and successful method to enhance failed canaloplasty.

Surgical feasibility and biocompatibility of wide-field dual-array suprachoroidal-transretinal stimulation prosthesis in middle-sized animals.

PURPOSE: To investigate the safety and efficacy of a newly-developed wide-field dual-array suprachoroidal-transretinal stimulation (STS) prosthesis in middle-sized animals. METHODS: The prosthesis consisted of two arrays with 50 to 74 electrodes. To test the feasibility of implanting the prosthesis and its efficacy, the prosthesis was implanted for 14 days into two rabbits. Optical coherence tomography (OCT) and ophthalmoscopy were performed 7 and 14 days after the implantation. Then the rabbits were euthanized, eyes were enucleated, and the posterior segment of the eye was examined histologically. In a second experiment, the arrays were implanted into two cats, and their ability to elicit neural responses was determined by electrically evoked potentials (EEPs) at the chiasm and by optical imaging of the retina. RESULTS: All arrays were successfully implanted, and no major complications occurred during the surgery or during the 2-week postoperative period. Neither OCT nor ophthalmoscopy showed any major complications or instability of the arrays. Histological evaluations showed only mild cellular infiltration and overall good retinal preservation. Stimulation of the retina by the arrays evoked EEPs recorded from the chiasm. Retinal imaging showed that the electrical pulses from the arrays altered the retinal images indicating an activation of retinal neurons. The thresholds were as low as 100 µA for a chiasm response and 300 µA for the retinal imaging. CONCLUSION: Implantation of a newly-developed dual-array STS prosthesis for 2 weeks in rabbits was feasible surgically, and safe. The results of retinal imaging showed that the dual-array system was able to activate retinal neurons. We conclude that the dual-array design can be implanted without complication and is able to activate retinal neurons and optic nerve axons.

Development of very large electrode arrays for epiretinal stimulation (VLARS).

BACKGROUND: Retinal implants have been developed to treat blindness causing retinal degenerations such as Retinitis pigmentosa (RP). The retinal stimulators are covering only a small portion of the retina usually in its center. To restore not only central vision but also a useful visual field retinal stimulators need to cover a larger area of the retina. However, large area retinal stimulators are much more difficult to implant into an eye. Some basic questions concerning this challenge should be answered in a series of experiments. METHODS: Large area retinal stimulators were fabricated as flexible multielectrode arrays (MEAs) using silicon technology with polyimide as the basic material for the substrate. Electrodes were made of gold covered with reactively sputtered iridium oxide. Several prototype designs were considered and implanted into enucleated porcine eyes. The prototype MEAs were also used as recording devices. RESULTS: Large area retinal stimulator MEAs were fabricated with a diameter of 12 mm covering a visual angle of 37.6° in a normal sighted human eye. The structures were flexible enough to be implanted in a folded state through an insertion nozzle. The implants could be positioned onto the retinal surface and fixated here using a retinal tack. Recording of spontaneous activity of retinal neurons was possible in vitro using these devices. CONCLUSIONS: Large flexible MEAs covering a wider area of the retina as current devices could be fabricated using silicon technology with polyimide as a base material. Principal surgical techniques were established to insert such large devices into an eye and the devices could also be used for recording of retinal neural activity.

Treatment exit options for non-infectious uveitis registry: participant characteristics at 3 years.

PURPOSE: The Treatment exit Options For non-infectious Uveitis (TOFU) registry documents disease courses for non-anterior non-infectious uveitis entities with and without treatment to generate more evidence for clinical management recommendations including treatment exit strategies. In this article, we present the participants' baseline characteristics after the first 3 years. METHODS: TOFU is an observational, prospective registry and recruits patients ≥18 years of age with non-anterior non-infectious uveitis with or without a history of previous disease-modifying antirheumatic drugs (DMARDs) treatment. The data are collected in the electronic data capture software REDCap and include ophthalmological and general medical history as well as clinical findings. RESULTS: Between 24.10.2019 and 27.12.2022, 628 patients were enrolled at 25 clinical sites in Germany and Austria. Patients with intermediate uveitis were most frequently included (n=252; 40.1%) followed by posterior uveitis (181; 28.8%), panuveitis (n=154; 24.5%) and retinal vasculitis (n=41, 6.5%). At baseline, 39.6% were treated with systemic corticosteroids, 22.3% with conventional synthetic (cs) DMARDs, 20.5% with biological (b) DMARDs and 3.6% with other systemic treatments. Average best corrected visual acuity (BCVA) was 0.69 decimal. Patients with panuveitis had the worst BCVA with 0.63 decimal. Overall, only 8 patients (1.3%) suffered from severe visual impairment. CONCLUSIONS: Less than half of participants required DMARD treatment at baseline, with csDMARDs used more frequently than bDMARDs. The presence of severe visual impairment was low, mostly affecting patients with panuveitis. These findings are in line with comparable monocentric cross-sectional studies of tertiary uveitis centres in Germany and will allow us to generate generalisable evidence in TOFU.

[Ab interno trabeculotomy without/with cataract operation-An alternative treatment before or instead of trabeculectomy in patients with high intraocular pressure?] / Ab-interno-Trabekulotomie ohne/mit Kataraktoperation ­ Eine Therapiealternative vor bzw. anstatt Trabekulektomie bei Patienten mit hohen Augeninnendrücken?

BACKGROUND: Trabeculotomy with the Kahook knife is a new ab interno minimally invasive glaucoma surgery (MIGS) procedure. The MIGS are usually performed in early to intermediate glaucoma eyes. In this retrospective study we analyzed the intraocular pressure (IOP) and topical glaucoma eye drop therapy (Meds) reduction achieved by the Kahook trabeculotomy (TO) without (n = 19) or with (n = 18) combined cataract operation (Cat-TO) as initial treatment before or to avoid filtering surgery. MATERIAL AND METHODS: A total of 37 eyes of 37 patients were examined when IOP was > 21 mm Hg in at least 2 examinations despite the maximum tolerable Meds applied. Cat-TO was performed in 18 phakic eyes (primary open-angle glaucoma, POAG = 11, pseudoexfoliation glaucoma, PEX = 5, ocular hypertension, OHT = 2). In 19 pseudophakic eyes (POAG = 12, PEX = 6, OHT = 1) an isolated TO was executed. Complete success (no Meds) and relative success (irrespective of Meds) for IOP ≤ 21 mm Hg, ≤ 18 mm Hg, ≤ 16 mm Hg were evaluated 2, 6 and 12 months postoperatively. RESULTS: The IOP was significantly reduced from preoperatively to 2 months after Cat-TO as well as after TO (Cat-TO: 26.8 ± 5.9 mm Hg to 16.0 ± 2.9 mm Hg, p < 0.001; TO: IOD 28.2 ± 5.6 mm Hg to 16.3 ± 3.5 mm Hg, p < 0.001). Meds reduction after Cat-TO as well as after TO was not significant (Cat-TO: 2.1 ± 1.3 to 1.3 ± 1.3, p = 0.11; TO: Meds 2.7 ± 1.1 to 2.2 ± 1.3, p = 0.23); however, Meds reduction after 6 and 12 months was significantly greater in the Cat-TO group compared to the TO group (p = 0.02). The IOP and Meds did not change significantly from 2 to 6 months. After Cat-TO, qualified success after 12 months for IOP ≤ 18 mm Hg was 61% (11/18) and for IOP ≤ 16 mm Hg 28% (5/18). After TO, qualified success after 12 months for TO was 47% (9/19) for IOP ≤ 18 mm Hg and 26% (5/19) for IOP ≤ 16 mm Hg. The intervention was not sufficient for 7 patients after TO and 2 patients after Cat-TO (IOP two times > 21 mm Hg). CONCLUSION: The first year results show that TO as well as Cat-TO are effective minimally invasive interventions to delay or even avoid a filtrating operation. In case of Meds intolerance and target IOP ≤ 16 mm Hg Cat-TO is not sufficient.

A workflow to visualize vertebrate eyes in 3D.

PURPOSE: To establish a workflow to visualize the surgical anatomy in 3D based on histological data of eyes of experimental animals for improving the planning of complex surgical procedures. METHODS: Four C57BL/6J wild-type(wt) mouse eyes, three Brown Norway rat eyes and four Chinchilla Bastard rabbit eyes were enucleated and processed for standard histology with serial sections and hematoxylin and eosin staining. Image stacks were processed to obtain a representation of the eye anatomy in 3D. In addition, virtual image stacks and 3D point clouds were generated by processing sagittal sections of eyes with stepwise 180° rotation and projection around the eye axis to construct a rotationally symmetric 3D model from one single sagittal section. RESULTS: Serial sections of whole eyes of mice, rats and rabbits showed significant artifacts interfering with a practical image stack generation and straightforward 3D reconstruction despite the application of image registration techniques. A workflow was established to obtain a 3D image of the eye based on virtual image stacks and point cloud generation by rotation of a single sagittal section of the eye around the symmetry axis. By analyzing the tissue shrinkage during histological processing true biometric reconstructions of the eyes were feasible making the resulting model usable for 3D modeling and simulation, e.g. for planning of complex surgical procedures in different species. CONCLUSION: Because serial sections of the eye with standard histological protocols yielded too many artifacts for a straightforward 3D visualization we reconstructed a pseudorealistic 3D model based on virtual image stacks and point cloud generation calculated from a single sagittal section of the eye. Such a model detailing microscopic structures of the whole eye will allow for a specific planning of surgical procedures in small animal eyes in order to prevent surgical complications in a very early stage of an experiment and it will support the design and development of complex intraocular implants. It will therefore be helpful in surgical teaching and improve laboratory animal welfare by an expected reduction of experimental animal numbers. Further processing including integration of mechanical tissue properties is needed to convert these 3D models into a practical virtual reality teaching and simulation platform for eyes of several species.

Safety and feasibility of sutureless pars-plana vitrectomy in sub-Tenon anesthesia (SAFE-VISA): a prospective study.

BACKGROUND: To determine the safety and feasibility of sutureless pars-plana vitrectomy (ppV) in sub-Tenon anesthesia. METHODS: In this prospective study. Pain and anxiety at various times after ppV using a visual analogue scale (VAS) and Wong-Baker-FACES scale as well as visual sensations during surgery were investigated. The surgeon evaluated motility, chemosis, overall feasibility. RESULTS: ppV was performed on 67 eyes (33 sub-Tenon anesthesia, 34 general anesthesia). Pain during surgery in sub-Tenon anesthesia was 1.8 ± 2.2 (0.0-8.0), anxiety was 2.3 ± 2.2 (0.0-8.5). There was a moderate correlation between pain and anxiety (R2 = 0.58). Comparing sub-Tenon and general anesthesia no difference in pain perception was found the day after surgery. 27.3% of patients saw details, 21.2% saw colors, 90.1% saw light/motion perception, 3.0% had no light perception. Median chemosis after surgery was 1.0 (IQR = 1.0). Median motility of the eye during surgery was 1.0 (IQR = 1.0), median grade was 1.0 (IQR = 1.0). 24.2% of patients showed subconjunctival hemorrhage during or after surgery. CONCLUSIONS: Sutureless pars-plana vitrectomy in sub-Tenon anesthesia was performed safely, with pain and anxiety levels tolerable for the patients and without the necessity for presence of an anesthesiologist. With 88.9% of patients willing to undergo vitreoretinal surgery in sub-Tenon anesthesia again, we recommend it as a standard option. Trial registration This study was approved by the Institutional Ethical Review Board of the RWTH Aachen University (EK 111/19). This study is listed on clinicaltrials.gov (ClinicalTrials.gov identifier: NCT04257188, February 5th 2020).

BioAdhere: tailor-made bioadhesives for epiretinal visual prostheses.

Introduction: Visual prostheses, i.e. epiretinal stimulating arrays, are a promising therapy in treating retinal dystrophies and degenerations. In the wake of a new generation of devices, an innovative method for epiretinal fixation of stimulator arrays is required. We present the development of tailor-made bioadhesive peptides (peptesives) for fixating epiretinal stimulating arrays omitting the use of traumatic retinal tacks. Materials and methods: Binding motifs on the stimulating array (poly[chloro-p-xylylene] (Parylene C)) and in the extracellular matrix of the retinal surface (collagens I and IV, laminin, fibronectin) were identified. The anchor peptides cecropin A (CecA), KH1, KH2 (author's initials) and osteopontin (OPN) were genetically fused to reporter proteins to assess their binding behavior to coated microtiter plates via fluorescence-based assays. Domain Z (DZ) of staphylococcal protein A was used as a separator to generate a bioadhesive peptide. Following ISO 10993 "biological evaluation of medical materials", direct and non-direct cytotoxicity testing (L-929 and R28 retinal progenitor cells) was performed. Lastly, the fixating capabilities of the peptesives were tested in proof-of-principle experiments. Results: The generation of the bioadhesive peptide required evaluation of the N- and C-anchoring of investigated APs. The YmPh-CecA construct showed the highest activity on Parylene C in comparison with the wildtype phytase without the anchor peptide. eGFP-OPN was binding to all four investigated ECM proteins (collagen I, laminin > collagen IV, fibronectin). The strongest binding to collagen I was observed for eGFP-KH1, while the strongest binding to fibronectin was observed for eGFP-KH2. The selectivity of binding was checked by incubating eGFP-CecA and eGFP-OPN on ECM proteins and on Parylene C, respectively. Direct and non-direct cytotoxicity testing of the peptide cecropin-A-DZ-OPN using L-929 and R28 cells showed good biocompatibility properties. Proof-of-concept experiments in post-mortem rabbit eyes suggested an increased adhesion of CecA-DZ-OPN-coated stimulating arrays. Conclusion: This is the first study to prove the applicability and biocompatibility of peptesives for the fixation of macroscopic objects.

The very large electrode array for retinal stimulation (VLARS)-A concept study.

OBJECTIVE: The restoration of vision in blind patients suffering from degenerative retinal diseases like retinitis pigmentosa may be obtained by local electrical stimulation with retinal implants. In this study, a very large electrode array for retinal stimulation (VLARS) was introduced and tested regarding its safety in implantation and biocompatibility. Further, the array's stimulation capabilities were tested in an acute setting. APPROACH: The polyimide-based implants have a diameter of 12 mm, cover approximately 110 mm2 of the retinal surface and carrying 250 iridium oxide coated gold electrodes. The implantation surgery was established in cadaveric porcine eyes. To analyze biocompatibility, ten rabbits were implanted with the VLARS device, and observed for 12 weeks using slit lamp examination, fundus photography, optical coherence tomography (OCT) as well as ultrasound imaging. After enucleation, histological examinations were performed. In acute stimulation experiments, electrodes recorded cortical field potentials upon retinal stimulation in the visual cortex in rabbits. MAIN RESULTS: Implantation studies in rabbits showed that the implantation surgery is safe but difficult. Retinal detachment induced by retinal tears was observed in five animals in varying severity. In five cases, corneal edema reduced the quality of the follow-up examinations. Findings in OCT-imaging and funduscopy suggested that peripheral fixation was insufficient in various animals. Results of the acute stimulation demonstrated the array's ability to elicit cortical responses. SIGNIFICANCE: Overall, it was possible to implant very large epiretinal arrays. On retinal stimulation with the VLARS responses in the visual cortex were recorded. The VLARS device offers the opportunity to restore a much larger field of visual perception when compared to current available retinal implants.

Relationships Between Spatial Contrast Sensitivity and Parafoveal Cone Density in Normal Subjects and Patients With Retinal Degeneration.

BACKGROUND AND OBJECTIVE: To investigate the relationship between spatial contrast sensitivity (CS) and parafoveal cone density (PCD). PATIENTS AND METHODS: Fifteen healthy individuals (mean age: 26.1 years ± 4.5 years) and nine patients with hereditary retinal degeneration (mean age: 31.6 years ± 13.4 years) without media opacities were studied. The CS was measured by CSV-1000 (VectorVision, Greenville, OH). The cone mosaic was photographed with an adaptive optics scanning laser ophthalmoscope (AOSLO) with a 1° × 1° field of view centered on the fovea. The PCD was calculated in an annular area with radii of 0.38° and 0.43°. The CS was converted to the logarithm (logCS), and the area under the logCS function (AULCSF) was determined. RESULTS: The AULCSF was significantly and positively correlated with the PCD in the control (R2 = 0.522; P = .003) and retinal degeneration (R2 = 0.514; P = .03) groups. CONCLUSION: PCD can predict the spatial contrast sensitivity in normal subjects or patients with retinal degeneration without media opacities. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:106-113.].

Relationship between reading performance and saccadic disconjugacy in patients with convergence insufficiency type intermittent exotropia.

PURPOSE: To determine the relationship between re-reading the same line and saccadic disconjugacy in patients with convergence insufficiency-type intermittent exotropia [CI-type X(T)]. METHODS: Eight patients with CI-type X(T) and ten healthy orthophoric individuals were studied. Video-oculography was used to assess the eye movements during the reading of a Japanese novel displayed on a 23-in. liquid crystal monitor placed 60 cm from the eyes. The sentences were displayed horizontally and read from left to right. The number of unintentional re-readings of the same line was counted, and the disconjugacy at the median of the saccade between the end of a line and the next line was determined. RESULTS: The number of re-readings of the same line in patients with CI-type X(T) was 4.9 ± 2.3 times which was significantly higher than that in the controls at 0.2 ± 0.4 times (P < 0.001). The saccadic disconjugacy was significantly larger in patients with CI-type X(T) at -1.70° ± 0.72° than that in the controls at -0.40°± 0.30° (P < 0.001). The number of re-readings of the same line was significantly and positively correlated with the saccadic disconjugacy (R = 0.84, R (2) = 0.71, P < 0.01). CONCLUSIONS: The results of our study indicate that saccadic disconjugacy is associated with re-reading the same line in patients with CI-type X(T).

Slow Cone Reflectance Changes during Bleaching Determined by Adaptive Optics Scanning Laser Ophthalmoscope in Living Human Eyes.

To investigate the changes in the reflectance of human cone photoreceptors by an adaptive optics scanning laser ophthalmoscope (AO-SLO) during photobleaching. A custom-built AO-SLO with an observation light of 840-nm was used to measure the cone densities and the reflectance changes during bleaching by 630 nm red light emitting diodes. Measurements were made at 1° and 3° temporal to the fovea within an area of 1° × 1° in 8 eyes of 8 normal subjects. After dark-adaptation, images of the cone mosaics were recorded continuously for 5-min before, 5-min during, and after 5-min of light stimulation with a sampling rate of 5-Hz. The first positive peak (P1) was observed at 72.2 ± 15.0-s and a second positive peak (P2) at 257.5 ± 34.5-s at 1°. The increase of the reflectance of P1 was significantly larger at 1° (34.4 ± 13.9%) than at 3° (26.0 ± 10.5%; P = 0.03, Wilcoxon's signed rank test). The average cone density at 1° (51123.13 ± 1401.23 cells/mm2) was significantly larger than that at 3° (30876.13 ± 1459.28 cells/mm2; P <0.001, Wilcoxon's signed rank test). The changes in the reflectance of the cones during bleaching by red light had two peaks. The two peaks may be caused by regeneration of cone photopigment during bleaching.