Swept-Source Anterior Segment Optical Coherence Tomography Imaging and Quantification of Bleb Parameters in Glaucoma Filtration Surgery.

This paper describes a technique for using swept-source anterior segment optical coherence tomography (AS-OCT) to visualize internal bleb microstructure and objectively quantify dimensions of the scleral flap and trabeculo-Descemet window (TDW) in non-penetrating glaucoma filtration surgery (GFS). This was a cross-sectional study of 107 filtering blebs of 67 patients who had undergone deep sclerectomy surgery at least 12 months prior. The mean post-operative follow-up duration was 6.5 years +/- 4.1 [standard deviation (SD)]. The maximal bleb height was significantly greater in the complete success (CS) blebs compared to the qualified success (QS) and failed (F) blebs (1.48 vs. 1.17 vs. 1.10 mm in CS vs. QS vs. F, one-way ANOVA, p < 0.0001). In a subcohort of deep sclerectomy blebs augmented by intraoperative Mitomycin-C, the trabeculo-Descemet window was significantly longer in the complete success compared to the qualified success group (613.7 vs. 378.1 vs. 450.8 µm in CS vs. QS vs. F, p = 0.004). The scleral flap length, thickness, and width were otherwise similar across the three outcome groups. The quantification of surgical parameters that influence aqueous outflow in non-penetrating GFS can help surgeons better understand the influence of these structures on aqueous outflow and improve surgical outcomes.

Low-Dose Propofol with Peribulbar Anaesthesia for Cataract Surgery.

In this paper, we investigate the effect of sedation using low-dose propofol on patient reported outcome measures (PROMS) in patients undergoing cataract surgery. This is a randomised, single-blinded observational prospective study. Patients undergoing elective cataract surgery using peribulbar anaesthesia over consecutive cataract lists were selected for this trial. Patients were randomised to receive either no sedation or low-dose propofol (20 to 30 mg followed by 10 mg increments until the patient developed slurred speech alone) prior to the administration of local anaesthesia. Pain, satisfaction, anxiety, needle recall, pulse, and blood pressure (BP) were measured. A total of 97 patients were included, 50 of whom received propofol. There were 4 senior surgeons and anaesthetists. There were no ocular or systemic complications and all patients had uncomplicated surgery. Anxiety (p = 0.026), needle recall (p < 0.001), difference in systolic BP (p = 0.043), and pulse (p = 0.046) were dependent on patient age (p < 0.001) and the use of propofol (p = 0.007). Lower pain was associated with propofol (p = 0.008), as well as lower anxiety (p = 0.002), and increased patient age (p = 0.014). The administration of propofol was significantly associated with lower needle recall (p < 0.001), pre- to post-operative difference in systolic BP (p = 0.029), and mean BP (p = 0.044). Low-dose propofol given immediately prior to administration of local anaesthesia was associated with reduced pain and needle recall, as well as lower BP.

Evidence of impaired mitochondrial cellular bioenergetics in ocular fibroblasts derived from glaucoma patients.

Glaucoma is a progressive optic neuropathy characterized by the neurodegeneration of the retinal ganglion cells (RGCs) resulting in irreversible visual impairment and eventual blindness. RGCs are extremely susceptible to mitochondrial compromise due to their marked bioenergetic requirements and morphology. There is increasing interest in therapies targeting mitochondrial health as a method of preventing visual loss in managing glaucoma. The bioenergetic profile of Tenon's ocular fibroblasts from glaucoma patients and controls was investigated using the Seahorse XF24 analyser. Impaired mitochondrial cellular bioenergetics was detected in glaucomatous ocular fibroblasts including basal respiration, maximal respiration and spare capacity. Spare respiratory capacity levels reflect mitochondrial bio-energetic adaptability in response to pathophysiological stress. Basal oxidative stress was elevated in glaucomatous Tenon's ocular fibroblasts and hydrogen peroxide (H2O2) induced reactive oxygen species (ROS) simulated the glaucomatous condition in normal Tenon's ocular fibroblasts. This work supports the role of therapeutic interventions to target oxidative stress or provide mitochondrial energetic support in glaucoma.

Long-term outcomes of viscocanalostomy and phaco-viscocanalostomy in patients with narrow angle glaucoma.

PURPOSE: To assess the outcomes of viscocanalostomy and phaco-viscocanalostomy in patients with narrow angle glaucoma at a single tertiary eye centre. METHOD: All patients undergoing viscocanalostomy for narrow angle glaucoma between June 2010 and June 2017 with a minimum follow-up of 12 months were included. Data was analysed from a prospectively maintained surgical outcome database. Primary outcome was a change in intraocular pressure (IOP). Secondary outcomes were changes in LogMAR visual acuity, number of eye drops, post-operative complications and further surgical interventions. Success was defined at two IOP cut-off points: IOP ≤ 21 mmHg and IOP ≤ 15 mmHg with (qualified success) or without (complete success) drops. Failure was any repeat glaucoma surgery or loss of light perception. RESULTS: Seventy eyes of 46 patients with a mean follow-up of 41.31 months (range 12-60 months) were included. Mean IOP changed from 25.7 ± 9.6 to 15.2, 15.6, 14.6, 13.8 and 14.0 mmHg at 1, 2, 3, 4 and 5 years post-operatively. Drops reduced from 3.2 ± 1.1 pre-operatively to 0.5 at 1 year and 1.1 at all time points thereafter. Qualified success for an IOP ≤ 21 mmHg was achieved in 94.2%, 88.1%, 92.5%, 91.1% and 92.0% and complete success in 63.8%, 37.3%, 30.2%, 22.2% and 24.0% in years 1 to 5, respectively. Qualified success for an IOP ≤ 15 mmHg was achieved in 53.6%, 60.9%, 69.8%, 68.9% and 64.0% and complete success in 39.1%, 26.9%, 22.6%, 20.0% and 8.0% in years 1 to 5, respectively. IOP was significantly lower at all examined post-operative time points (41.1%, 39.3%, 43.3%, 46.4% and 45.3% at years 1 to 5, respectively, p < 0.001 at all time points). Four eyes (5.7%) failed to meet any of the success criteria. Of these, 3 eyes (4.3%) required further glaucoma surgery and one eye (1.4%) progressed to no perception of light at 48 months. No patients had an IOP ≤ 5 mmHg on two consecutive occasions after 3 months. CONCLUSION: Viscocanalostomy and phaco-viscocanalostomy are a safe and effective surgical option in the management of chronic narrow angle glaucoma.

Deep sclerectomy and trabeculectomy augmented with Mitomycin C: 2-year post-operative outcomes.

PURPOSE: Two-year post-operative outcomes of both deep sclerectomy (DS) and trabeculectomy surgery (Trab) augmented with Mitomycin C (MMC) at a single tertiary eye centre. METHODS: Retrospective review of DS + MMC and trabeculectomy + MMC at a single centre between February 2015 and March 2018. Patients with a minimum of 12-month follow-up were included. Post-operative follow-up: day 1, week 1, months 1/3/6/12/18/24. Primary outcomes: changes in intraocular pressure (IOP) and changes in LogMAR visual acuity (BCVA) pre- and post-procedure. SECONDARY OUTCOMES: changes in number of eye drops, number of follow-up clinic visits, post-operative complications and further surgical interventions. Complete success: IOP ≤ 21 mmHg off all IOP-lowering medications. Qualified success: IOP ≤ 21 mmHg on medication. Failure: IOP > 21 mmHg at 24 months or ≤ 5 mmHg on 2 consecutive follow-up visits after 3 months +/- additional incisional glaucoma surgery +/- loss of light perception. Statistical analysis performed using Microsoft Excel + SPSS. RESULTS: 90 eyes: DS + MMC = 46 eyes, Trab + MMC = 44 eyes. DS + MMC v Trab + MMC: mean pre-op IOP = 19.57 mmHg v 18.89 mmHg, significantly reduced at all post-operative time-points for both groups (p < 0.001). Mean IOP reduction from baseline = 33.94% v 38.39%; > 30% IOP reduction = 54.35% v 68.18%. IOP ≤ 16 mmHg = 82.61% (38/46) v 95.46% (42/44), IOP ≤ 12 mmHg = 52.17% (24/46) v 72.72% (32/44). Complete success = 67.39% v 61.36%, qualified success = 26.09% v 29.55%, failure = 6.52% v 9.09%. Post-op BCVA: no statistically significant differences between two groups (p = 0.09). Mean pre-op drops v post-op drops = 2.98 v 0.38 (DS + MMC; p < 0.001); 2.68 v 0.39 (Trab + MMC; p < 0.001). Further surgical intervention = 13% v 29.55%. Mean number of post-op clinic visits DS + MMC v Trab + MMC = 10.09 v 13.02 (p = 0.005). CONCLUSION: Both procedures achieve sustained intraocular pressure and drop reduction at 2 years post-op. DS + MMC has lower complication rates requiring less intervention and significantly fewer clinic visits, which may be an important factor for deciding surgical management of glaucoma patients in the era of Covid-19 to reduce patient/clinician exposure to the virus.

Corneal biomechanics and biomechanically corrected intraocular pressure in primary open-angle glaucoma, ocular hypertension and controls.

AIMS: To compare the biomechanically corrected intraocular pressure (IOP) estimate (bIOP) provided by the Corvis-ST with Goldmann applanation tonometry (GAT-IOP) in patients with high-tension and normal-tension primary open-angle glaucoma (POAG; HTG and NTG), ocular hypertension (OHT) and controls. Moreover, we compared dynamic corneal response parameters (DCRs) of the Corvis-ST in POAG, OHT and controls, evaluated the correlation between global visual field parameters mean deviation and pattern SD (MD and PSD) and DCRs in the POAG group. METHODS: 156 eyes of 156 patients were included in this prospective, single-centre, observational study, namely 41 HTG and 33 NTG, 45 OHT cases and 37 controls. Central corneal thickness (CCT), GAT-IOP and bIOP were measured, GAT-IOP was also adjusted for CCT (GATAdj). DCRs provided by Corvis-ST were evaluated, MD and PSD were recorded by 24-2 full-threshold visual field. To evaluate the difference in DCRs between OHT, HTG and NTG, a general linear model was used with sex, medications and group as fixed factors and bIOP and age as covariates. RESULTS: There was a significant difference between GAT-IOP, GATAdj and bIOP in NTG and HTG, OHT and controls. NTG corneas were significantly softer and more deformable compared with controls, OHT and HTG as demonstrated by significantly lower values of stiffness parameters A1 and highest concavity and higher values of inverse concave radius (all p<0.05). There was a significant correlation (p<0.05) between MD, PSD and many DCRs with POAG patients with softer or more compliant corneas more likely to show visual field defects. CONCLUSIONS: Corneal biomechanics might be a significant confounding factor for IOP measurement that should be considered in clinical decision-making. The abnormality of corneal biomechanics in NTG and the significant correlation with visual field parameters might suggest a new risk factor for the development or progression of NTG.

Thrombospondin-2 is up-regulated by TGFß2 and increases fibronectin expression in human trabecular meshwork cells.

Elevated intraocular pressure (IOP) is a major risk factor for the development of primary open-angle glaucoma (POAG). This is from an increased aqueous humour (AH) outflow resistance through the trabecular meshwork (TM). The pathogenic mechanisms leading to the increase in TM outflow resistance are poorly understood but are thought to be from a dysregulation of the TM extracellular matrix (ECM) environment. ECM modification and turnover are crucial in regulating the resistance to aqueous outflow. ECM turnover is influenced by a complex interplay of growth factors such as transforming growth factors (TGFß) family and matrix metalloproteinases (MMPs). Elevated TGFß2 levels result in an increase in ECM deposition such as fibronectin leading to increased resistance. Fibronectin is a major component of TM ECM and plays a key role in its maintenance. Thrombospondins (TSP)-1 and -2 are important regulators of the ECM environment. TSP-1 has been implicated in the pathogenesis of POAG through activation of TGFß2 within the TM. TSP-2 does not contain the catalytic domain to activate latent TGFß, but is able to mediate the activities of MMP 2 and 9, thereby influencing ECM turnover. TSP-2 knock out mice show lower IOP levels compared to their wild type counterparts, suggesting the involvement of TSP-2 in the pathogenesis of POAG but its role in the pathogenesis of POAG remains unclear. The purpose of this study was to investigate the role of TSP-2 in trabecular meshwork ECM regulation and hence the pathogenesis of POAG. TSP-1 and TSP-2 expressions in immortalised glaucomatous TM cells (GTM3) and primary human non-glaucomatous (NTM) and glaucomatous cells (GTM) were determined by immunocytochemistry, immuno-blot analysis and qPCR following treatment with TGFß2 and Dexamethasone. The level of ECM protein fibronectin was determined in TM cells using immuno-blot analysis following treatment with TSP-1 or -2. TM cells secrete TSP-1 and -2 under basal conditions at the protein level and TSP-2 mRNA and protein levels were increased in response to TGFß2 three days post treatment. Exogenous treatment with TSP-2 up-regulated the expression of fibronectin protein in GTM3 cells, primary NTM and GTM cells. TSP-1 did not affect fibronectin protein levels in GTM3 cells. This suggests that the role of TSP-2 might be distinct from that of TSP-1 in the regulation of the TM cell ECM environment. TSP-2 may be involved in the pathogenesis of POAG and contribute to increased IOP levels by increasing the deposition of fibronectin within the ECM in response to TGFß2.

Outcome of Descemet stripping automated endothelial keratoplasty in eyes with an Ahmed glaucoma valve.

PURPOSE: The purpose was to investigate the survival of Descemet stripping automated endothelial keratoplasty (DSAEK) in eyes with an Ahmed glaucoma valve (AGV). METHODS: The study had a retrospective case-series of patients with an AGV in the anterior chamber undergoing a DSAEK. Included in the analysis were graft size, number of previous operations, post-operative glaucoma medications, post-operative intraocular pressure (IOP) control, graft size and donor factors (age, endothelial cell density, and post-mortem time). A generalised linear model with binary logistic regression was used to test for an effect on graft survival at 1 year and 1.5 years. RESULTS: Fourteen eyes from 13 patients were included. The survival rate of the first DSAEK at 6, 12, 18, 24 and 30-months was 85%, 71%, 50%, 36% and 30%, respectively. The mean duration to graft failure was 12.9 ± 6.2 months. Five of the seven failed first grafts went on to have a repeat DSAEK. The mean follow-up in this subgroup was 30.7 ± 18.4 months. The survival rate of second DSAEK at 6, 12, 18 and 24 months was 100% (5/5), 100% (5/5), 75% (3/4) and 67% (2/3). Only one second DSAEK failed in the duration of the study and went on to receive a third DSAEK which failed at 18-months. The mean IOP within the first year was significantly lower for grafts that survived at 1 and 1.5 years (17.4 mmHg, 16.9 mmHg) than for grafts that failed (19.4 mmHg, 19.4 mmHg) (p = 0.04, p = 0.009). CONCLUSION: DSAEK is a viable alternative to PK to restore visual function in eyes with an AGV sited in the anterior chamber. IOP is an important risk factor for graft failure.

Measurement and computer modeling of temporary arrangements of polygonal actin structures in trabecular meshwork cells which consist of cross-linked actin networks and polygonal actin arrangements.

PURPOSE: In trabecular meshwork (TM) cells, actin geodesic arrangements were measured and then subjected to computational modeling to appreciate the response of different dome shapes to mechanical force. METHODS: Polygonal actin arrangements (PAAs) and cross-linked actin networks (CLANs) were induced and imaged by Alexa Flour(®) 488 Phalloidin in bovine TM and human TM cells. Masked images were examined for size, circularity, and spoke and hub dimensions using ImageJ. Finite element modeling was used to create idealized dome structures and "realistic" PAA and CLAN models. The models were subjected to different loads simulating concentrated force and distortion measured. RESULTS: We provide evidence that PAAs and CLANs are not identical. Both structures formed flattened domes but PAAs were 6 times larger than CLANs, significantly more circular and had greater height. The dimensions of the triangulations of hubs and spokes were, however, remarkably similar. Hubs were around 2 µm(2) in area, whereas spokes were about 5 µm in length. Our modeling showed that temporary arrangements of polygonal actin structures (TAPAS) were because of their flattened shape, more resistant to shearing than compression when compared with idealized domes. CLANs were marginally more resistant to shearing than PAAs but because of size much more resistant to compression. CONCLUSIONS: Evidence is provided that there are 2 types of actin icosahedrons in cultured TM cells we collectively call TAPAS. Modeling suggests that TAPAS have rigidity and are better at dealing with shearing than compression forces. The 2 types of TAPAS, PAAs, and CLANs, have much in common but there are size and mechanical response differences that need to be taken into account in future experimentation.

Mersey deanery ophthalmology trainees' views of the objective assessment of surgical and technical skills (OSATS) workplace-based assessment tool.

Objective assessment of surgical and technical skills (OSATS) workplace-based assessment tool is now mandatory during ophthalmology speciality training in the United Kingdom. The opinions of those undergoing this assessment have not been formally sought. This study evaluated the views of ophthalmology trainees on OSATS assessment as applied to cataract surgery. A questionnaire was circulated to 34 ophthalmology speciality trainees of the Mersey deanery. A total of 28 responses were received. The most positive aspects of the process identified were feedback, learning and opportunity for reflective practice. The most negative aspects were time constraints, assessor's availability and case selection. Of the trainees, 93 % mentioned that no previous agreed action was taken into consideration when filling in subsequent forms and their performance was not discussed in their annual summative assessment. This study highlights important aspects of trainees' perceptions of OSATS. Trainees appreciate the formative aspects of OSATS assessment. Some problems came to light, which can be resolved by specification of standards, training of assessors, and commitment from both trainers and trainees. Changes are needed to allow demonstration of surgical progression with time. The issues identified here will be relevant to other specialities as well. A larger survey would be beneficial.