No side effects on rabbit retina or vitreous microenvironment by nd:YAG laser vitreolysis.

BACKGROUND: To explore the safety of Neodymium:Yttrium-aluminum-garnet (Nd:YAG) laser vitreolysis based on the histological examination of the retina and the alteration of vitreous cytokines in the rabbits. METHODS: Nine male New Zealand rabbits underwent Nd:YAG laser vitreolysis of 10 mJ x 500 pulses in the left eyes, while the right eyes were used as controls. Intraocular pressure, color fundus photography, and ultrasound B scan were measured before, as well as 1 day, 4 weeks, and 12 weeks after Nd:YAG laser vitreolysis. Three rabbits were euthanized 1 day, 4 weeks, and 12 weeks after treatment, respectively. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and hematoxylin-eosin (H&E) staining were used to look for pathological changes in the retina. An enzyme-linked immunosorbent assay (ELISA) was utilized to detect the expression of vascular endothelial growth factor (VEGF) and some inflammatory cytokines, including interferon inducible protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1) and interlenkin 6 (IL-6) in the vitreous humor. The ascorbic acid (AsA) and total reactive antioxidant potential (TRAP) in the vitreous humor were also measured. RESULTS: Following Nd:YAG laser vitreolysis, the levels of VEGF, IP-10, MCP-1, IL6, AsA, and TRAP in the vitreous humor did not change substantially (P > 0.05). There were no detectable pathological changes in the retinal tissues, and no apoptotic signal was found. CONCLUSIONS: Rabbits tolerate Nd:YAG laser vitreolysis without observable impact on retinal tissue or the microenvironment of the vitreous.

Injectable in situ cross-linking hyaluronan hydrogel for easier removal of posterior vitreous cortex in vitrectomy.

PURPOSE: Removing transparent vitreous tissues, such as a residual vitreous cortex (VC) or proliferative membrane, without damaging the retina is often problematic in vitrectomy. We examined the feasibility of an injectable in situ cross-linking hyaluronan hydrogel (XL-HA) for vitrectomy. STUDY DESIGN: Experiments using ex vivo and in vivo animal models. METHODS: HA-dibenzocyclooctyne and HA-azidoethylamine solutions were mixed to form XL-HA, which then gradually formed a hydrogel. We tested the function of XL-HA in ex vivo porcine eyes. We then examined the performance of XL-HA in in vivo rabbit models of posterior vitreous detachment, posterior VC removal, and proliferative vitreoretinopathy. RESULTS: The ex vivo study showed that XL-HA rapidly embedded triamcinolone acetonide, mimicking VC attached to the retina, and became hard enough to be pinched with tweezers within 3 minutes, allowing us to remove only the triamcinolone acetonide without impairing the internal limiting membrane. In the in vivo rabbit models, XL-HA injection improved posterior vitreous detachment, and the thin and fragile posterior VC or fibrous proliferative membrane was readily peeled off without any damage to the underlying retina as compared with untreated controls. A short-term intraocular biocompatibility test demonstrated that the intraocular pressure remained normal with XL-HA injected into the eye. In addition, transmission electron microscopy showed no obvious abnormalities in the cornea or in the inner and outer retina. CONCLUSION: The results indicate that XL-HA is a potential adjunctive device to help make vitrectomy safe, effective, and successful.

Efficacy and safety of early YAG laser vitreolysis for symptomatic vitreous floaters: the study protocol for a randomized clinical trial.

BACKGROUND: Vitreous floaters are a common ocular condition that affects individuals of all ages. Although vitreous floaters are typically benign, they can significantly impair visual acuity and quality of life. Laser vitreolysis, which uses an Nd: YAG laser to vaporize collagenous vitreous opacities, is increasingly being used as a treatment option. However, there is currently a lack of evidence regarding its efficacy and the appropriate timing of its application. This study aims to evaluate the efficacy and safety of early intervention with YAG laser vitreolysis in treating symptomatic vitreous floaters. METHODS: The present study is a randomized, controlled, double-blind clinical trial. A total of 70 participants with symptomatic floaters for 1 month were prospectively recruited. These participants will be randomly assigned to two groups, with 35 individuals in each group: the early treatment group and the delayed treatment group. Participants assigned to the early treatment group will undergo YAG laser vitreolysis immediately, followed by a sham laser treatment 3 months later. On the other hand, participants assigned to the delayed treatment group will receive a sham laser treatment and then undergo YAG laser vitreolysis 3 months later. The follow-up time points will be 1, 3, 6, and 12 months from randomization. Primary outcomes will be participants' self-reported improvement in visual disturbance on a scale of 1 to 10 and their scores on the National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25). Secondary outcomes will be an objective evaluation of the effectiveness of the treatment in reducing vitreous floaters through OCT and fundus photography and tracking any adverse events related to the eyes or overall health. DISCUSSION: This clinical trial aims to evaluate the effectiveness of YAG laser vitreolysis in treating symptomatic vitreous floaters and assess the safety of performing early intervention with YAG laser vitreolysis. TRIAL REGISTRATION: ClinicalTrials.gov NCT05800353 . Registered on 10 March 2023.

Study on maintenance of eyeball morphology by foldable capsular vitreous body in severe ocular trauma.

OBJECTIVES: To explore the feasibility and safety of using a foldable capsular vitreous body (FCVB) in managing severe ocular trauma and silicone oil-dependent eyes. METHODOLOGY: This is a retrospective study of 61 ocular trauma patients (61 eyes) who presented to the Department of Eye Emergency, Hebei Eye Hospital from May 1, 2018, to May 31, 2019, including 51 male patients (51 eyes) and 10 female patients (10 eyes) with an average age of 44.98 ± 14.60 years old. The oldest patient was 75 years old, and the youngest was 8 years old. These cases represented 51 eyes with severe eyeball rupture and 10 eyes with severe, complicated ocular trauma, which became silicone oil-dependent after the operation. These patients received FCVB implants, and data regarding their visual acuity, intraocular pressure, changes in eye axis, cornea, retina, and FCVB state were recorded after the operation. RESULTS: In all patients, the FCVB was properly positioned and well supported with the retina. All 61 patients cleared a follow-up window of 1-36 months with no reports of important changes in their visual acuity. Among the patients, 91.8% reported normal intraocular pressure, the retinal reattachment rate reached 100%, and the eyeball atrophy control rate reached 100%. There was no report of rupture of the FCVB, allergies to silicone, intraocular infection, intraocular hemorrhage, silicone oil emulsification, or sympathetic ophthalmia. CONCLUSIONS: Foldable capsular vitreous bodies (FCVBs) designed to mimic natural vitreous bodies are suitable as long-term ocular implants that can provide sustained support for the retina without the need for any special postoperative postures. Their barrier function may effectively prolong the retention time of the tamponade and prevent various complications caused by direct contact of the eye tissues with the tamponade.

A modified 23-G trocar and cannula system with lateral micropores for drainage of vitreous humor.

When primary angle-closure glaucoma occurs during an acute attack, routine phacoemulsification is challenging because of the high intra-ocular pressure (IOP) and shallow anterior chamber (AC). To reduce IOP and deepen the AC before phacoemulsification, a portion of the vitreous body is often removed. In this report, we introduce an extended trocar/cannula system with lateral micropores to drain the liquid vitreous before routine phacoemulsification to solve this problem. A modified trocar was used to drain the liquefied vitreous before routine phacoemulsification. We demonstrated that this novel trocar/cannula system is safe and effective for draining liquefied vitreous before routine phacoemulsification. It also facilitates the transition to smooth phacoemulsification.

Measurement of vitreous humor pressure in vivo using an optic fiber pressure sensor.

We conducted a study to assess the pressure difference between the aqueous and vitreous humors in rabbit eyes using a direct intraocular pressure (IOP) measurement method. A micro-optic-fiber pressure sensor was utilized for this purpose. Preliminary experiments with enucleated porcine eyes confirmed the sensor's accuracy in measuring both aqueous and vitreous humor pressure. The main study involved six healthy albino rabbits, where the sensor measured the pressure in the anterior chamber (aIOP) and posterior vitreous-cavity (pIOP). These measurements were compared to aIOP values obtained through rebound tonometry. Additionally, pre- and postoperative pressure comparisons were made after performing a vitrectomy. Results revealed a significant disparity between aqueous and vitreous humor pressures. Prior to vitrectomy, pIOP was 22.8 mmHg, over twice as high as aIOP (11.0 mmHg), but decreased to a similar level following the procedure. Comparison between the sensor measurements and rebound tonometry showed agreement in aIOP values. In conclusion, our study demonstrates that vitreous humor pressure is consistently higher than aqueous humor pressure, reaching the upper limit of normal IOP. Furthermore, vitrectomy effectively reduces pIOP, aligning it with aIOP. These findings contribute valuable insights into intraocular pressure dynamics and have implications for clinical interventions targeting ocular pressure regulation.

[Role of vitreous in the pathogenesis of neovascular age-related macular degeneration]. / Die Rolle des Glaskörpers in der Pathogenese der exsudativen altersabhängigen Makuladegeneration.

Age-related changes in vitreous molecular and anatomic morphology begin early in life and involve two major processes: vitreous liquefaction and weakening of vitreo-retinal adhesion. An imbalance in these two processes results in anomalous posterior vitreous detachment (PVD), which comprises, among other conditions, vitreo-macular adhesion (VMA) and traction (VMT). VMA is more common in patients with neovascular age-related macular degeneration (nAMD) than age-matched control patients, with the site of posterior vitreous adherence to the inner retina correlating with location of neovascular complexes. The pernicious effects of an attached posterior vitreous on age-related macular degeneration (AMD) progression involve mechanical forces, enhanced fluid influx and inflammation in and between the retinal layers, hypoxia leading to an accumulation of vascular endothelial growth factor (VEGF) and other stimulatory cytokines, and probably an infiltration of hyalocytes. It has been shown that vitrectomy not only mitigates progression to end-stage AMD, but existing choroidal neovascularization regresses after surgery. Thus, surgical PVD induction during vitrectomy or by pharmacologic vitreolysis may be considered in non-responders to anti-VEGF treatment with concomitant VMA.

Kaminari Kagura: the "lightning bolt shape" technique for posterior vitreous detachment induction.

PURPOSE: To describe and evaluate the effectiveness of the Kaminari Kagura technique as a posterior hyaloid detachment treatment. STUDY DESIGN: This was a prospective, consecutive, randomized interventional study. METHODS: This study examined 30 eyes from 30 patients divided into two groups: (1) a Kaminari Kagura group (15 eyes) and (2) a control group (15 eyes) scheduled for vitrectomy with an optical coherence tomography (OCT)-based diagnosis of adherent posterior hyaloid. RESULTS: The mean time for posterior vitreous detachment (PVD) induction in the Kaminari Kagura group was 58 ± 6.6 s, and that in the control group was 69 ± 9 s (p < 0.005). No intra- or post-operative complications were reported. CONCLUSIONS: The Kaminari Kagura technique results in effective posterior hyaloid detachment in less time than that required for posterior vitreous cortex engagement.

Experimental Assessment of the Performance of Dual Pneumatic Vitreous Cutters According to Gauge and Cut Rate.

PURPOSE: To compare and analyze the performance of dual pneumatic ultra-high-speed vitreous cutters based on their cut rates, vacuum levels, and diameters in terms of flow rate and cutting time. METHODS: The Constellation Vision System was used to remove egg white for 30 seconds, after which we calculated the flow rate by measuring the change in weight. We then measured the time required to remove 4 mL of egg white. We tested the UltraVit (UV) 7,500 cuts per minute (cpm) probe and the Advanced UltraVit (AUV) 10,000 cpm probe in biased open duty cycle mode, using 23-, 25-, and 27-gauge probes, respectively. RESULTS: In biased open duty cycle, the flow rate tended to decrease as the cut rates increased for all three gauges. At the same cut rates, the flow rate increased as the vacuum level increased (p < 0.05), and as the diameter increased (p < 0.05). Among cutters with the same diameter, the AUV cutter showed higher flow rates than the UV cutter, with increases of 0.267 mL/min (18.5%) at 27 gauge, 0.627 mL/min (20.8%) at 25 gauge, and 1.000 mL/min (20.7%) at 23 gauge (all p < 0.05). The times required to remove 4 mL of egg white took longer with the UV cutter than the AUV cutter for all three gauges (all p < 0.05). CONCLUSIONS: The use of a smaller gauge vitreous cutter may reduce the flow rate and increase the time required for vitrectomy, but this can be partially compensated for by increasing the vacuum level as well as using a vitreous cutter with a higher maximum cut rate, improved port size, and improved duty cycle.

Practical applications of vitreous imaging for the treatment of vitreous opacities with YAG vitreolysis.

PURPOSE: To demonstrate the methodology and efficacy of using scanning laser ophthalmoscopy (SLO) and dynamic optical coherence tomography (OCT) to identify and treat symptomatic vitreous floaters using yttrium-aluminum garnet laser vitreolysis (YLV). METHODS: This is a case series highlighted from a cross sectional retrospective study conducted at the Vitreous Retina Macula Specialists of Toronto. Forty eyes from thirty-five patients were treated with YLV between November 2018 and December 2020 for symptomatic floaters and imaged with SLO and dynamic OCT. Patients were re-treated with YLV if they reported ongoing significant vision symptoms during follow-up which correlated to visible opacities on exam and or imaging. Three cases will be highlighted to present the practical applications of SLO and dynamic OCT imaging for YLV treatment. RESULTS: Forty treated eyes were enrolled in this study, with twenty-six eyes (65%) requiring at least one repeat YLV treatment following the first treatment due to ongoing symptomatic floaters. Following the first YLV, there was a significant improvement in overall mean best corrected visual acuity compared to before treatment (0.11 ± 0.20 LogMAR units vs. 0.14 ± 0.20 LogMAR units, p = 0.02 (paired t test)). Case 1 demonstrates a dense, solitary vitreous opacity that has been localized with dynamic OCT imaging to track its movements and retinal shadowing with the patient's eye movements. Case 2 shows the utility of adjusting the fixation target to monitor the movement of vitreous opacities in real-time. Case 3 exhibits an association between decreased symptom burden and vitreous opacity density after YLV. CONCLUSION: Image-guided YLV facilitates the localization and confirmation of vitreous opacities. SLO and dynamic OCT of the vitreous can provide a real-time evaluation of floater size, movement, and morphology, to help clinicians target treatment and monitoring of symptomatic floaters.

Different strokes for anterior capsulorhexis in pediatric cataract.

Background: A successful outcome in pediatric cataract surgery is determined by an intact, curvilinear anterior capsulotomy which is dependent on the type and density of cataract, the morphology of the anterior capsule, and associated anterior segment pathologies. Purpose: This video highlights 10 different techniques which can be used for capsulorhexis in pediatric cataract. Synopsis: The choice of technique for capsulorhexis in pediatric cataract is on case basis, namely the gold standard manual capsulotomy aided by rhexis forceps (1. Standard capsulorhexis/2. Vitrector, Vitrectorhexis), with an assistance from capsular staining (3. Blue-rhexis), or by coaxial illumination (4. Coaxial-rhexis) or by just the sheen of capsule (5. Sheen-rhexis). The anterior chamber can be maintained using ophthalmic visco-elastic device (Visco-rhexis) or by irrigation fluid (6. Hydro-rhexis). A speed-breaker in the routine capsulotomy is the presence of plaque which is managed by rhexis forceps (7. Plaque-rhexis) or by a vitrector (vitrectorhexis) or a pair of micro-scissors (8. Scissor rhexis). Above all, the technology of femto-second-laser-assisted (9. Femto-rhexis) and zepto-pulse-precision capsulotomy (10. Zepto-rhexis) is also illustrated. Highlights: This video highlights the 10 different techniques of capsulorhexis in pediatric cataract surgery. Video Link: https://youtu.be/TgDrk5RYdbI.

New Terminology and Methodology for the Assessment of the Vitreous, Its Floaters and Opacities, and Their Effect on Vision: Standardized and Kinetic Anatomical and Functional Testing of Vitreous Floaters and Opacities (SK VFO Test).

OBJECTIVE: To introduce VFO and SK VFO Test: new, more representative terminology for symptoms of vitreous floaters/opacities (VFO) and new standardized kinetic (SK) anatomical-functional assessment. MATERIALS AND METHODS: Eight eyes underwent before-after limited vitrectomy (LV): best-corrected visual acuity, low-luminance visual acuity, Minnesota Low Vision Reading Chart near visual acuity in logMAR, contrast sensitivity function (CV1000E), and straylight measurements (SM) (HDA/LDA/C-Quant). SK infrared confocal scanning laser ophthalmoscopy (SK IRcSLO) and swept-source widefield optical coherence tomography (SS-WF-OCT) identified VFO and posterior vitreous detachment (PVD). SK IRcSLO was performed with gaze directed towards the extreme superior, inferior, and lateral directions. RESULTS: Anatomical-functional results after LV improved in 7 eyes (87.5%): objective scatter index (27.34%), disturbance index (47.97%) and C-Quant Log units (2.26%). Pre-LV SK IRcSLO and SS-WFOCT imaging identified dynamic well-defined VFO and PVD status (100%). A residual asymptomatic anterior cortical vitreous-induced shadowing ripple effect was detected post-LV. CONCLUSIONS: This is the first objective-standardized test accounting for VFO kinesis and intermittent effect. There is potential for personalizing treatment and establishing best candidates for laser or surgery. [Ophthalmic Surg Lasers Imaging Retina 2023;54:306-315.].

[The development of laser technologies in vitreoretinal surgery (publications review)].

The article presents review of scientific publications on development of laser treatment methods in vitreoretinal surgery. The use of photo-therapy in medicine dates back to ancient times, when people began to use sunlight as treatment of various diseases. The heyday of photo-therapy falls on the second half of the XIX century, which was associated with the invention of first electric lamps. In 1960, T. Maiman developed the world's first laser, revolutionizing precision and control of light delivery. This was the beginning of heyday of laser surgery primarily in ophthalmology, where potential of lasers was instantly recognized. The subsequent discovery of argon laser in 1964 by W. Bridges (USA) marked new era in retinal photo-coagulation. Then new types of lasers with various systems of delivering laser radiation appeared that significantly expanded range of application of laser technologies in ophthalmology and vitreoretinal surgery. Currently, the lasers are applied in oculoplasty, refractive and corneal surgery, in laser support of phacoemulsification of cataract, in treatment of glaucoma, in laser coagulation of retina and thermotherapy. In vitreoretinal surgery laser technologies remain at the level of the XX century. Thus, they are still applied only for endolaser coagulation of retina. And this despite the fact that there is immense potential for applying lasers as "laser scalpel" to remove vitreous humor, epiretinal fibrosis, retinotomy and choroidotomy.

Ocular Tuberculosis in Pediatrics: A Case Report.

A 17-year-old male was taken to the emergency department for decreased left visual acuity and floaters beginning that same day. There was a history of exposure to pulmonary tuberculosis five years before (mother as index case) followed by a four-month period of isoniazid prophylaxis. The ophthalmic examination showed posterior and intermediate uveitis in the left eye. Laboratory tests were normal; IgG for herpes simplex 1 was positive and both the varicella-zoster virus and remaining serologic tests were negative. Chest radiography was normal. Two weeks later, an epiretinal membrane with risk of tractional retinal detachment was observed. The Mantoux tuberculin skin test showed an induration of 15 mm and the IGRA test was positive. Sputum and vitreous humor samples were collected. Quadruple therapy and prednisolone were started. Ten days later, a posterior vitreous detachment with underlying vitreous hematoma was observed. Posterior vitrectomy and peripheral endolaser were performed without complications. One month later, the microbiological results became available, with the identification of Mycobacterium tuberculosis. Corticosteroids were weaned progressively. Antituberculous drugs were maintained for six months. The patient made a full recovery.

Clinical Efficacy and Safety of Foldable Capsular Vitreous Body Implant Surgery in 22 Cases of Silicone Oil-dependent Eyes.

OBJECTIVE: This study aimed to evaluate the clinical efficacy and safety of foldable capsular vitreous body (FCVB) implant surgery in silicone oil-dependent eyes. METHODS: A total of 22 participants with silicone oil-dependent eyes who received treatment with FCVB implant surgery between January 2019 and June 2020 were included in this retrospective study. The intraocular pressure (IOP), best-corrected visual acuity (BCVA), demographic data, and any recorded complications were evaluated. RESULTS: The postoperative IOP (12.73±4.20 mmHg) was significantly improved (P=0.03) compared to the preoperative IOP (10.23±3.69 mmHg) (the main endpoint). There was no significant difference (P=0.33) in the final BCVA preoperation and 3rd month postoperation (the secondary endpoint). The most common postoperative complication was hyphema. Other common postoperative complications included corneal opacity, a shallow anterior chamber, and a low IOP. CONCLUSION: FCVB implant surgery is a safe and effective method for treating silicone oil-dependent eyes; however, attention should be paid to the prevention and timely treatment of complications.

Ultrasonic Vitrectomy Performance Assessment Using Micro-Extensional Rheology.

Purpose: The purpose of this study was to assess the performance of ultrasonic (US) vitrectomy devices by quantifying and comparing its impact on extracted vitreous properties to conventional pneumatic blade (PB) cutters using micro-extensional rheology. US vitrectomy is a new technology that offers an alternative to PB cutters used in vitreo-retinal surgeries. Methods: Thirty-six porcine vitreous samples were extracted using US and PB cutters. Each sample was kept at 4°C and tested within 24 hours postmortem and 4 hours post-vitrectomy. A recently developed micro-extensional rheology technique is used to infer the relative protein fragment size of extracted vitreous by quantifying the extensional relaxation time. Results: US-extracted vitreous exhibited extensional relaxation times orders of magnitude lower than PB-extracted vitreous (0.37 ms and 27.25 ms, respectively). Relaxation time is directly correlated to the fragment size of the collagen fibers in the vitreous. The formation of beads-on-a-string droplets within the PB samples indicates the presence of larger collagen fragments. These droplets were not seen on US samples. Conclusions: This new micro-extensional rheology technique can identify significant differences in physical properties of extracted vitreous. Long relaxation times and beads-on-a-string droplets within the PB vitreous samples indicate larger protein fragments compared to the US samples. Translational Relevance: Higher fragmentation of vitreous and lower extensional relaxation times may improve retina safety due to a reduction in vitreo-retinal traction resulting from the continuous shear action and aspiration applied by ultrasonic vitrectomy technology.

Comparison of simultaneous vs sequential pars plana vitrectomy and cataract surgery.

BACKGROUND: To compare the clinical outcomes of patients undergoing sequential pars plana vitrectomy (PPV) followed by cataract extraction surgery (CE) [PPV/CE], simultaneous PPV and CE (PPV + CE), and sequential CE followed by PPV [CE/PPV]. METHODS: A retrospective observational cohort study of 427 eyes of 404 patients who underwent either sequential or simultaneous PPV and CE surgery between March 2016 and May 2021. Pre-operative and post-operative assessments (up to 2 years of follow-up visits) of uncorrected visual acuity (UCVA), corrected distance visual acuity (CDVA), spherical equivalent (SEQ), and refractive prediction error (RPE) was done. Main outcome measures were both visual (UCVA, CDVA) and refractive (RPE, SEQ). RESULTS: There was a statistically significant difference in CDVA of the PPV/CE, PPV + CE, CE/PPV groups (logMAR 0.34 ± 0.40, 0.65 ± 0.61, and 0.55 ± 0.60, respectively) at one month postoperatively (POM1) (P < 0.001), and at the POM12 visits (logMAR 0.25 ± 0.34, 0.53 ± 0.68, and 0.44 ± 0.48; P = 0.04). In the subgroup analysis of patients with a diagnosis of either epiretinal membrane or vitreous opacities, there was no statistically significant difference in SEQ (P = 0.09) and RPE (P = 0.13) at the combined 1 month and 3 month visits. CONCLUSION: Simultaneous PPV and cataract surgery demonstrated similar improvements in visual acuity and refractive outcomes, as well as comparable intraoperative and postoperative complication profiles to sequential surgery.

FULL-THICKNESS MACULAR HOLE WITH PERSISTENT BROAD VITREOMACULAR ATTACHMENT: Clinical Characteristics and Surgical Outcomes.

PURPOSE: To describe the characteristics and surgical outcomes of full-thickness macular holes (FTMHs) with persistent broad vitreomacular attachment. METHODS: This was a retrospective, observational case series. Consecutive patients undergoing pars plana vitrectomy for FTMHs with persistent broad vitreomacular attachment (study group) were reviewed. Clinical charts, optical coherence tomography (OCT) features of macular holes, and surgical outcomes were reviewed and compared with those with typical FTMH with focal vitreomacular traction (control group). RESULTS: A total of 15 eyes of 14 consecutive patients (eight males and six females with a mean age of 60.6 years) were included in the study group. OCT showed a zone of at least 1,500 µm all around the circumference of the fovea where the vitreous was attached. On OCT, epiretinal membrane and epiretinal proliferation were observed in 73% and 87% of cases, respectively. Compared with the control group, the study group was younger (P = 0.027) and had better preoperative visual acuity (P = 0.007). All FTMHs closed after one surgery in both groups, and the postoperative visual acuity of the study group was better than that of the control group (P = 0.002). CONCLUSION: Full-thickness macular holes may have developed under the condition that the vitreous cortex was broadly attached around the hole. These FTMHs were associated with younger age, better baseline visual acuity, and a higher incidence of epiretinal membranes and epiretinal proliferations compared with macular hole with focal vitreomacular traction. The surgical outcome was favorable, but the pathogenesis of FTMH development remains unclear.

Translation of hyaluronic acid-based vitreous substitutes towards current regulations for medical devices.

PURPOSE: Hydrogel-based vitreous substitutes have the potential to overcome the limitations of current clinically used endotamponades. With the goal of entering clinical trials, the present study aimed to (I) transfer the material synthesis of hyaluronic acid-based hydrogels into a routine, pharmaceutical-appropriate production and (II) evaluate the properties of the vitreous substitutes in terms of the current regulations for medical devices (MDR/ISO standards). METHODS: The multistep manufacturing process of the vitreous substitutes, including the modification of hyaluronic acid with glycidyl methacrylate, photocopolymerization with N-vinylpyrrolidone, and successive hydrogel purification, was developed under laboratory conditions, characterized using 1 H-NMR, FT-IR and UV/Vis spectroscopies and HPLC, and transferred towards a pharmaceutical production environment considering GMP standards. The optical and viscoelastic characteristics of the hyaluronic acid-based hydrogels were compared with those of extracted human vitreous and silicone oil. The effect of the hydrogels on the metabolic activity, proliferation and apoptosis of fibroblast (MRC-5, BJ, L929), retinal pigment epithelial (ARPE-19, hiPSC-derived RPE) and photoreceptor cells (661W) was studied as well as their mucosal tolerance via a HET-CAM assay. RESULTS: Hyaluronic acid-based hydrogels having a suitable purity, sterility, high transparency (>90%), appropriate refractive index (1.3365) and viscoelasticity (G' > G″) were prepared in a standardized manner under controlled process conditions. The metabolic activity, proliferation and apoptosis of various cell types as well as egg choroid were unaffected by the hyaluronic acid-based vitreous substitutes, demonstrating their biocompatibility. CONCLUSIONS: The present study demonstrates the successful transferability of the crucial synthesis steps of hyaluronic acid-based hydrogels into a routine, GMP-compliant production process while achieving the optical and viscoelastic properties, biocompatibility and purity required for their clinical use as vitreous substitutes.