Photovoltaic, wireless wide-field epiretinal prosthesis to treat retinitis pigmentosa.

PURPOSE: To develop and evaluate a photovoltaic, wireless wide-field epiretinal prosthesis for the treatment of retinitis pigmentosa. METHODS: A mosaic array of thinned silicon-based photodiodes with integrated thin-film stimulation electrodes was fabricated with a flexible polyimide substrate film to form a film-based miniaturized electronic system with wireless optical power and signal transmission and integrated electrostimulation. Manufactured implants were characterized with respect to their optoelectronic performance and biocompatibility following DIN EN ISO 10993. RESULTS: A 14 mm diameter prosthesis containing 1276 pixels with a maximum sensitivity at a near infrared wavelength of 905 nm and maximized stimulation current density 30-50 µm below the electrodes was developed for direct activation of retinal ganglion cells during epiretinal stimulation. Fabricated prostheses demonstrated mucosal tolerance and the preservation of both metabolic activity, proliferation and membrane integrity of human fibroblasts as well as the retinal functions of bovine retinas. Illumination of the prosthesis, which was placed epiretinally on an isolated perfused bovine retina, with infrared light resulted in electrophysiological recordings reminiscent of an a-wave (hyperpolarization) and b-wave (depolarization). CONCLUSIONS: A photovoltaic, wireless wide-field epiretinal prosthesis for the treatment of retinitis pigmentosa using near infrared light for signal transmission was designed, manufactured and its biocompatibility and functionality demonstrated in vitro and ex vivo.

New suture probe canaloplasty combined with suprachoroidal collagen implantation.

PURPOSE: To present the modified surgery technique of new suture probe canaloplasty with a specially prepared monofilament 4.0 polypropylene suture combined with suprachoroidal drainage (ScD) and collagen sheet implantation for non-penetrating glaucoma surgery. METHODS: Prospective study with a twelve months follow-up. A standard 4/0 polypropylene suture (ProleneTM by Ethicon; thickness: approximately 250 m) is cut and shaped with an ophthalmic knife (MANI® Crescent Knife, Mani Inc 8-3 Kiyohara Industrial Park, Utsunomiya, Tochigi 321-3231, Japan) to create a blunt end without sharp or compressed edges. This improves suture probe canaloplasty by providing a more stable and smoother probing device. Schlemm's canal is prepared using the standard technique of canaloplasty with suprachoroidal drainage. Then, instead of using the canaloplasty microcatheter or the previously published 6/0 double-helix suture, Schlemm's canal is probed with the blunt ending of the 4/0 Prolene suture. After successful 360-degree probing, a doubled 10/0 polypropylene tension suture is threaded through the tip of the 4/0 suture. The 4/0 suture is then pulled back and the 10/0 tension sutures are tied at both ends to tension Schlemm's canal. A special collagen sheet (Ologen®) is placed in suprachoroidal space, and the scleral flap is firmly sewed. RESULTS: 115 eyes were included in this prospective study. In 113 cases the Schlemm's canal could completely be probed with the suture probe and canaloplasty with ScD and collagen sheet implantation succeeded. In two cases the intervention was transformed to 360-degree suture trabeculotomy due to an intraoperative cheese-wiring. Twelve months after successful new suture probe canaloplasty with ScD and Collagen Implantation the IOP had decreased by 37.1% (from 21.6 ± 6.0 mmHg with 3.3 different IOP lowering eye drops to 13.5 ± 3.5 mmHg with 1.0 eye drops). 16 Patients did not achieve sufficient IOP levels and underwent 360-degree suture trabeculotomy during the follow-up. One patient had to be treated with further glaucoma surgery to achieve a sufficient IOP level. Complications were hyphema, postoperative IOP elevation and transient hypotony. No serious or sight-threatening complications occurred. CONCLUSION: New suture probe canaloplasty with ScD and collagen sheet implantation yields the opportunity to conduct a cost-effective canaloplasty easier and less complicated than with the previously described method with the twisted 6/0 suture. The safety profile and IOP lowering effect is comparable. In cases where complete probing fails, there is still the opportunity to switch to suture trabeculotomy over the majorly probed part of Schlemm's canal. The pressure lowering effect of the deep sclerectomy with ScD and suprachoroidal collagen sheet implant seems to have an additional impact on the sufficient pressure lowering procedure.

Long-Term Astigmatism after Intraocular Pressure Sensor Implantation and Nonpenetrating Glaucoma Surgery - EYEMATE-SC Trial.

PURPOSE: To investigate the long-term astigmatism after combined non-penetrating glaucoma surgery (NPGS) and implantation of the first miniaturized suprachoroidal intraocular pressure (IOP) sensor EYEMATE-SC. SETTING: The study was conducted in five medical centers in two different countries. DESIGN: Retrospective multicenter clinical study. METHODS: Astigmatism of patients instrumented with the EYEMATE-SC IOP sensor was assessed over a follow-up period of three years. Refraction and corrected distance visual acuity (CDVA) were obtained preoperatively, after 6 months, 1, 2, and 3 years. A canaloplasty-operated patient cohort served as control. Astigmatism was evaluated using 3-dimensional power vector analysis involving the spherical equivalent M, and the Jackson crossed cylinder projections J0 and J45. Exclusion criteria included neovascular and angle-closure glaucoma, myopia, axial length outside 22 to 26 mm, other ocular diseases, prior glaucoma surgery, other ocular surgery within 6 months (cataract surgery within 3 months) prior to NPGS, serious generalized conditions, and other active medical head/neck implants. RESULTS: Multivariate analysis indicated no changes in astigmatism along the observation period in both the EYEMATE-SC (n = 24) and the canaloplasty (n = 24) group (P > 0.05 or nonsignificant after Bonferroni correction). Astigmatism was unchanged between the EYEMATE-SC and the canaloplasty group at all time points (P > 0.05). CDVA didn't change along the observation period of three years in each of both groups (P > 0.05). CONCLUSIONS: Despite its suprachoroidal localization, the present study indicates that the miniaturized EYEMATE-SC IOP sensor doesn't negatively affect the long-term astigmatism after combined implantation with NPGS.

Descemet Membrane Endothelial Keratoplasty (DMEK) Anesthesia Analysis.

PURPOSE: Comparison of safety and clinical results of Descemet membrane endothelial keratoplasty (DMEK) in topical, peribulbar, or general anesthesia. METHODS: Retrospective, post hoc matched study of 346 patients who received DMEK surgery with different types of anesthesia (n = 54 topical, n = 137 peribulbar, n = 155 general anesthesia). Outcome criteria were intraoperative complications, endothelial cell count (ECC), central corneal thickness (CCT) and graft rejection rate, rebubbling rate, and visual acuity (VA). Mean follow-up time was 9.4 ± 2.8 months. RESULTS: The group with topical anesthesia showed intraoperative difficulties such as vitreous pressure (p = 0.01) and difficult graft unfolding (p = 0.4), possibly leading to a higher rebubbling rate (p = 0.03) and therefore graft failure (p = 0.39). However, rebubbling and graft failure occurred more often when the graft preparation was more difficult (p = 0.2, p = 0.13, respectively), which was independent of anesthesia. All three groups achieved comparable functional results regarding VA, ECC, and CCT after 6 months. CONCLUSION: DMEK under topical anesthesia is feasible and shows comparable final visual outcomes but should be limited to selected cooperative patients and performed by experienced surgeons due to the potential for increased intraoperative challenges.

[Molecular diagnostics for vitreoretinal lymphoma]. / Molekulare Diagnostik des vitreoretinalen Lymphoms.

Primary vitreoretinal lymphoma (PVRL) represents a subtype of intraocular lymphomas, which are a subgroup of malignant lymphomas of the eye. PVRL is considered a special form of primary diffuse large cell lymphoma (DLBCL) of the CNS (central nervous system) (PCNSL) and arises primary or secondary to PCNSL. According to the cell of origin (COO) classification of DLBCL, PVRL largely belongs to the activated B­cell (ABC) type of DLBCL. Based on a recently established genetic-biological classification of DLBCL, PCNSL and thus also PVRL belong to a group of DLBCL of the MYD88/CD79B-mutated (MCD) or cluster 5 subtype, which often shows extranodal manifestations and MYD88 and CD79A mutations as well as CDKN2A deletions.PVRL diagnostics is often complicated as it represents a classic masquerade syndrome. Due to the usually limited material with often large numbers of reactive lymphocytes and/or degenerative changes in the cells, the results of diagnostic tests are difficult to interpret. Classic diagnostic tests include cytology on vitreous aspirates, immunocytochemistry, and clonality analysis.New insights into the spectrum of genetic alterations of vitreoretinal lymphomas (VRL) confirm the close relationship to PCNSL and could significantly improve pathological diagnosis. Next-generation sequencing panel-based diagnostics allow VRL diagnosis confirmation with little DNA in almost 100% of patients in cases with insufficient cytological evidence or lack of clonality detection. PVRL, as well as secondary vitreoretinal lymphomas after PCNSL or extracerebral DLBCL, have high mutation frequencies in characteristically mutated genes in PCNSL or MCD/cluster 5 type DLBCL. Supporting diagnostics, mutation detection can also be performed on cell-free DNA from the vitreous supernatant.

Advances in Canaloplasty-Modified Techniques Yield Strong Pressure Reduction with Low Risk Profile.

For decades, trabeculectomy (TE) was considered the gold standard for surgical treatment of open-angle glaucoma owing to its powerful intraocular pressure (IOP)-lowering potency. However, owing to the invasive nature and high-risk profile of TE, this standard is changing, and minimally invasive procedures are becoming more preferable. In particular, canaloplasty (CP) has been established as a much gentler alternative in everyday life and is under development as a full-fledged replacement. This technique involves probing Schlemm's canal with a microcatheter and inserting a pouch suture that places the trabecular meshwork under permanent tension. It aims to restore the natural outflow pathways of the aqueous humor and is independent of external wound healing. This physiological approach results in a significantly lower complication rate and allows considerably simplified perioperative management. There is now extensive evidence that canaloplasty achieves sufficient pressure reduction as well as a significant reduction in postoperative glaucoma medications. Unlike MIGS procedures, the indication is not only mild to moderate glaucoma; today, even advanced glaucoma benefits from the very low hypotony rate, which largely avoids a wipeout phenomenon. However, approximately half of patients are not completely medication-free after canaloplasty. As a consequence, a number of canaloplasty modifications have been developed with the goal of further enhancing the IOP-lowering effect while avoiding the risk of serious complications. By combining canaloplasty with the newly developed suprachoroidal drainage procedure, the individual improvements in trabecular facility and uveoscleral outflow facility appear to have an additive effect. Thus, for the first time, an IOP-lowering effect comparable to a successful trabeculectomy can be achieved. Other implant modifications also enhance the potential of canaloplasty or offer additional benefits such as the possibility of telemetric IOP self-measurement by the patient. This article reviews the modifications of canaloplasty, which has the potential to become a new gold standard in glaucoma surgery via stepwise refinement.

A rabbit model for outer retinal atrophy caused by surgical RPE removal.

PURPOSE: We aimed to establish a rabbit model with retinal atrophy induced by an iatrogenic retinal pigment epithelium (RPE) removal, for future testing of the efficacy and safety of cell therapy strategies. METHODS: A localized detachment of the retina from the RPE/choroid layer was created in 18 pigmented rabbits. The RPE was removed by scraping with a custom-made extendable loop instrument. The resulting RPE wound was observed over a time course of 12 weeks with optical coherence tomography and angiography. After 4 days (group 1) and 12 weeks (group 2), histology was done and staining with hematoxylin and eosin, as well as immunofluorescence performed to further investigate the effects of debridement on the RPE and the overlying retina. RESULTS: Already after 4 days, we observed a closure of the RPE wound by proliferating RPE and microglia/macrophage cells forming a multilayered clump. This pattern continued over the observation time course of 12 weeks, whereby the inner and outer nuclear layer of the retina became atrophic. No neovascularization was observed in the angiograms or histology. The observed changes were limited to the site of the former RPE wound. CONCLUSIONS: Localized surgical RPE removal induced an adjacent progressive retinal atrophy. Altering the natural course of this model may serve as a basis to test RPE cell therapeutics.

Safety and performance assessment of hyaluronic acid-based vitreous substitutes in patients with phthisis bulbi.

PURPOSE: To assess the safety and performance of hyaluronic acid-based vitreous substitutes in phthitic eyes. METHODS: In this retrospective interventional study a total of 21 eyes from 21 patients with phthisis bulbi were treated at the Eye Clinic Sulzbach between August 2011 and June 2021. Patients who underwent a 23G pars plana vitrectomy received a vitreous substitute composed of (I) a non-crosslinked hyaluronic acid (Healon GV), (II) a crosslinked hyaluronic acid-based hydrogel (UVHA), or (III) silicone oil (SO-5000). Main outcome measures were the intraocular pressure (IOP), the visual acuity and the structural integrity of the retina and choroid assessed by optical coherence tomography. RESULTS: An increase in IOP ≥ 5 mmHg was achieved with SO-5000 in 5/8 eyes (6/10 interventions, 60.0%) for 36.4 ± 39.5 days, with Healon GV in 4/8 eyes (7/11 interventions, 63.6%) for 82.6 ± 92.5 days and with UVHA in 4/5 eyes (5/6 interventions, 83.3%) for 93.6 ± 92.5 days. Visual acuity increased in 5/21 eyes (23.8%), remained constant in 12/21 eyes (57.1%) and decreased in 4/21 eyes (19.0%). No enucleations were required during the mean follow-up time of 192 ± 182 days. The OCT images indicated the preservation of retinal structures, while choroidal folds were only diminished in UVHA eyes. CONCLUSIONS: Hyaluronic acid-based hydrogels are biocompatible vitreous substitutes in humans and can increase and stabilize IOP in patients with phthisis bulbi for about 3 months.

One Year Results of the Preserflo MicroShunt Implantation for Refractory Glaucoma.

PRCIS: The Preserflo MicroShunt is an effective method to achieve a satisfying intraocular pressure (IOP) reduction in patients with complicated forms of glaucoma. PURPOSE: To evaluate the efficacy and safety of the Preserflo MicroShunt with mitomycin C in patients with complicated glaucoma. METHODS: This prospective interventional study included all patients that underwent Preserflo MicroShunt Implantation between April 2019 and January 2021 to treat severe and therapy refractory glaucoma. The patients either suffered from primary open angle glaucoma with already failed incisional glaucoma surgery or presented severe forms of secondary glaucoma (eg, after penetrating keratoplasty or globe penetrating injury). Primary endpoint was the IOP-lowering effect and the success rate after 12 months. Secondary endpoint was the occurrence of intraoperative or postoperative complications. Complete success was defined as reaching the target IOP (>6 mm Hg and <14 mm Hg) without additional IOP-lowering medication whereas qualified success was attained with the same IOP target regardless of the medication. RESULTS: A total of 40 eyes of 38 patients were enrolled. After 12 months 85.7% of the eyes achieved complete success with an average IOP of 10.5 ± 2.0 mm Hg, without the use of glaucoma eye drops. The average IOP reduction was 58.4% from baseline. In 5 cases (12.5%) failure occurred as revisional surgery was required. CONCLUSION: The Preserflo MicroShunt for refractory glaucoma cases achieved a high complete success rate without additional medication at 1 year. Revisional surgery was needed in some cases and long-term studies are needed.

Efficacy of a new fragmentation pattern in femtosecond laser-assisted cataract surgery with the Ziemer FEMTO LDV Z8.

PURPOSE: To determine the efficacy of different fragmentation patterns in femtosecond laser-assisted cataract surgery (FLACS) using Ziemer FEMTO LDV Z8. METHODS: We compared three different types of surgery: conventional cataract surgery (CCS), FLACS with conventional radial slices (named No-Spiderweb), and FLACS with a novel fragmentation pattern (radial slices combined with one or two rings) called "Spiderweb." Visual acuity (VA), nuclear opacity (NO) according to the Lens Opacities Classification System (LOCS lll), effective phacoemulsification time (EPT) and vacuum time were obtained for 845 eyes. RESULTS: Using FLACS (Spiderweb + No-Spiderweb), EPT was significantly reduced by 26% compared to CCS (FLACS: 2.46 ± 2.60 s; CCS: 3.34 ± 2.89 s; ΔM = - 0.88 s, p < .001). Furthermore, EPT as a function of progression of lens opacity was found to be not only lower in Spiderweb compared to CCS, but also in comparison with No-Spiderweb. At NO3, a significant reduction of 65% in EPT was observed by using Spiderweb compared to CCS (Spiderweb: 0.68 ± 1.23 s; CCS: 1.96 ± 1.53 s; ΔM = - 1.28 s, p <.001). Interestingly, EPT at NO3 was also significantly reduced by 57% in Spiderweb compared to No-Spiderweb (Spiderweb: 0.68 ± 1.23 s; No-Spiderweb: 1.57 ± 1 .59 s; ΔM = - 0.90 s, p <.001). The use of Spiderweb only marginally extends the vacuum time compared to No-Spiderweb by 11 s (Spiderweb: 209.13 ± 35.83 s; No-Spiderweb: 198.35 ± 36.84 s; p = .003) and the postoperative improved VA showed no significant difference among the different types of surgery (all ps ≥ .05). CONCLUSION: FLACS significantly reduces EPT compared to CCS. Furthermore, the novel Spiderweb pattern significantly reduces EPT in patients with a cataract of NO3 compared to CCS, but also to FLACS with the existing radial pattern (No-Spiderweb).

Recurrent corneal erosions related to an ocular injury 15 years before presentation.

Purpose: To report the case of a patient who presented with recurrent corneal erosions caused by an undetected plastic foreign body in the upper eyelid, which had remained asymptomatic for nearly 15 years following an ocular injury. Observations: A 39-year-old patient presented with recurrent corneal erosions and frontal headaches of unknown aetiology over the preceding eight months. The patient had previously been seen by twelve different ophthalmologists and had been treated over a 6-month period with a bandage contact lens, and therapeutic corneal scraping had been performed twice. However, the corneal erosion had repeatedly reappeared after removal of the bandage contact lens. On clinical examination prior to a planned phototherapeutic keratectomy, we extracted a 1.5 cm plastic foreign body, localised in the subtarsal area of the upper conjunctival fornix. Upon specific questioning, the patient denied any recent trauma, but reported a work-related accident with an accompanying eye injury 15 years before presentation. Conclusions and importance: Posttraumatic foreign bodies in the eye may remain asymptomatic for prolonged periods before giving rise to clinical signs such as recurrent corneal erosions. Hence, a thorough clinical examination with meticulous eyelid eversion should always be performed in such patients.

Safety and performance of a suprachoroidal sensor for telemetric measurement of intraocular pressure in the EYEMATE-SC trial.

AIM: To investigate the safety and performance of a telemetric suprachoroidal intraocular pressure (IOP) sensor (EYEMATE-SC) and the accuracy of its IOP measurements in open angle glaucoma (OAG) patients undergoing simultaneous non-penetrating glaucoma surgery (NPGS). METHODS: Prospective, multicentre, open-label, single-arm, interventional clinical trial. Twenty-four eyes of 24 patients with OAG regularly scheduled for NPGS (canaloplasty or deep sclerectomy) were simultaneously implanted with an EYEMATE-SC sensor. Six-month follow-up on the sensor's safety and performance as well as on the level of agreement between the EYEMATE-SC measurements and IOP measurements with Goldmann applanation tonometry (GAT). RESULTS: The eyes underwent canaloplasty (n=15) or deep sclerectomy (n=9) and achieved successful implantation of the sensor. No device migration, dislocation or serious device-related complications occurred. A total of 367 comparisons were included in the IOP agreement analysis. The overall mean difference between GAT and EYEMATE-SC measurements was 1.31 mm Hg (lower limit of agreement (LoA) 7.55 mm Hg; upper LoA -4.92 mm Hg). The maximum difference of 2.5 mm Hg ±3.96 (LoA 0.30-2.29) was reached on day 10 and continuously improved to an agreement of -0.15 mm Hg ±2.28 (LoA -1.24 to 0.89) after 6 months. Accordingly, the percentage of eyes within an IOP difference of ±5 mm Hg improved from 78% (day 3) to 100% (6 months). CONCLUSIONS: After 6 months, the EYEMATE-SC sensor was safe and well tolerated, and allowed continual IOP monitoring. TRIAL REGISTRATION NUMBER: NCT03756662.

MODIFIED SUTURELESS INTRASCLERAL FIXATION TECHNIQUE FOR SECONDARY INTRAOCULAR LENS IMPLANTATION: A Pilot Study.

BACKGROUND/PURPOSE: To demonstrate possible complications of a new intraocular lens for sutureless secondary scleral implantation and modifications of the surgical technique to optimize outcomes. METHODS: A retrospective study of 16 eyes (16 patients) who underwent a secondary intraocular lens implantation using the Carlevale intraocular lens (Soleko, Italy) with two anchor haptics for intrascleral implantation (mean follow-up 2.2 months). RESULTS: The visual acuity did not improve statistically significantly postoperatively ( P = 0.601). Seven (44%) patients suffered from postoperative hypotonia (intraocular pressure <5 mmHg) during the first three postoperative days. CONCLUSION: Owing to the early postoperative hypotony, we decided to modify the surgical technique. We present several suggestions to optimize the technique and outcome such as positioning the sclerotomies at the 2 and 8 o'clock positions, using 27 G trocars alone and suturing the frown incisions using self-resorbing sutures.

Measurement of intraocular temperature in glaucoma: week-day and seasonal fluctuations.

PURPOSE: To evaluate long-term intraocular temperature (IOT) variations in eyes with primary open-angle glaucoma (POAG) using an intraocular telemetric sensor. METHODS: This prospective, open-label, multicentre observational study analysed the IOT variations in 22 eyes of 22 patients with POAG. All enrolled patients underwent implantation of an intraocular pressure (IOP) sensor during cataract surgery. The telemetric system uses a built-in temperature sensor to control measured IOP for temperature. Each time a patient measures their IOP, both the IOP and IOT are recorded in the reader device. Patients were instructed to self-measure their IOP as often as desired, but at least four times daily. Recorded readings were retrieved and analysed using mixed effect models and pairwise comparisons using Bonferroni correction to assess the statistical significance of average IOT variations between each individual weekday and calendar month. RESULTS: The mean age of patients was 67.8±6.8 years and 36.4% were women. A total of 132 745 readings over 21 102 measurement-days were obtained. On average, IOT was significantly higher on Sundays (34.57°C; 95% CI 34.37 to 34.78) than on any other day of the week (p<0.001). Mean IOT on other weekdays ranged from 34.48°C to 34.51°C. Over the year, IOT followed a clear seasonal pattern, reaching its maximum in July (34.8°C; 95% CI 34.56 to 34.97) and its minimum in January (34.4°C; 95% CI 34.15 to 34.56; p<0.001). CONCLUSIONS: This study demonstrates the feasibility of continual and long-term measurement of IOT using intraocular sensors. The results show significant short-term and long-term fluctuations of IOT. Research is warranted to understand the impact of IOT variations on IOP, ocular perfusion and glaucoma progression.

Safety and effectiveness of pre-emptive diabetic vitrectomy in patients with severe, non-fibrotic retinal neovascularisation despite panretinal photocoagulation.

OBJECTIVES: To investigate the safety and effectiveness of pre-emptive vitrectomy in eyes with severe non-fibrotic proliferative diabetic retinopathy. METHODS: A multi-centre, retrospective, observational study. Pre-emptive vitrectomy was performed in non-fibrotic diabetic eyes with a visual acuity (VA) of 20/50 or better, where there was extensive persistent neovascularisation despite prior panretinal photocoagulation, and where the fellow eye had established sight loss despite vitrectomy for tractional complications. The primary outcome measure was the VA at last visit. RESULTS: Twenty patients were included. The mean age was 39 ± 14 years. Fifteen patients were Type 1 diabetic. The median baseline VA was 20/30 and remained stable at 20/28 at last visit (median follow-up period: 24 months). Eight eyes (40.0%) developed post-operative vitreous cavity haemorrhage; 4 of which required a vitreous cavity washout procedure. There were no post-operative retinal detachments. The index eye remained the significantly better eye at all time points bar one month post-surgery. Regression of retinopathy grading was observed in all eyes. CONCLUSION: In this pilot study, we found no sight loss with pre-emptive diabetic vitrectomy. Better eye status was maintained in this high-risk group. Further study with larger number of patients and longer-term follow-up is indicated.