Evaluation of Verteporfin as a Novel Antifibrotic Agent in a Rabbit Model of Glaucoma Filtration Surgery: A Pilot Study.

Purpose: Verteporfin is a benzoporphyrin derivative which is Food and Drug Administration-approved for treatment of choroidal neovascularization in conjunction with photodynamic therapy. It has been shown to prevent fibrosis and scar formation in several organs and represents a promising novel antifibrotic agent for glaucoma surgery. The goal of this study is to determine the effect of verteporfin on wound healing after glaucoma filtration surgery. Design: Preclinical study using a rabbit model of glaucoma filtration surgery. Subjects: Eight New Zealand white rabbits underwent glaucoma filtration surgery in both eyes. Methods: Eyes were randomized into 4 study groups to receive a postoperative subconjunctival injection of 1 mg/mL verteporfin (n = 4), 0.4 mg/mL mitomycin C (MMC; n = 4), 0.4 mg/mL MMC + 1 mg/mL verteporfin (n = 4), or balanced salt solution (BSS) control (n = 4). Bleb survival, vascularity, and morphology were graded using a standard scale over a 30-day period, and intraocular pressure (IOP) was monitored. At 30 days postoperative or surgical failure, histology was performed to evaluate for inflammation, local toxicity, and scarring. Main Outcome Measures: The primary outcome measure was bleb survival. Secondary outcome measures were IOP, bleb morphology, and bleb histology. Results: Compared to BSS control blebs, verteporfin-treated blebs demonstrated a trend toward increased surgical survival (mean 9.8 vs. 7.3 days, log rank P = 0.08). Mitomycin C-treated blebs survived significantly longer than verteporfin-treated blebs (log rank P = 0.009), with all but 1 MMC-treated bleb still surviving at postoperative day 30. There were no significant differences in survival between blebs treated with combination verteporfin + MMC and MMC alone. Mitomycin C-treated blebs were less vascular than verteporfin-treated blebs (mean vascularity score 0.3 ± 0.5 for MMC vs. 1.0 ± 0.0 for verteporfin, P < 0.01). Bleb histology did not reveal any significant toxicity in verteporfin-treated eyes. There were no significant differences in inflammation or scarring across groups. Conclusions: Although verteporfin remained inferior to MMC with regard to surgical survival, there was a trend toward increased survival compared with BSS control and it had an excellent safety profile. Further studies with variations in verteporfin dosage and/or application frequency are needed to assess whether this may be a useful adjunct to glaucoma surgery. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Intrastromal Corneal Ring Segment Implantation Followed by Simultaneous Topography-Guided Photorefractive Keratectomy and Corneal Cross-Linking for Contact Lens-Intolerant Keratoconus.

PURPOSE: This study aimed to evaluate the efficacy and safety of Keraring implantation followed by simultaneous topography-guided photorefractive keratectomy (TGPRK) and corneal cross-linking (CXL) in the management of keratoconus. METHODS: This is a single-center, private practice, retrospective review. Patients with keratoconus who were intolerant to contact lens wear underwent implantation of the Keraring, followed by TGPRK with CXL from 2 to 36 months after implantation. Main outcome measures were uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refraction (cylinder and spherical equivalent), keratometry (steep, maximum, and central), and central corneal thickness (CCT). Patients were followed up for 3 to 60 months postoperatively. RESULTS: Fifty-seven eyes from 45 patients were included. The mean time between Keraring and TGPRK/CXL was 6.0 ± 6.0 months. Patients were followed up for a mean of 28.6 ± 20.1 months after Keraring insertion. At 12-month follow-up, there was a statistically significant improvement in mean UDVA (0.94 ± 0.49-0.35 ± 0.23, P < 0.01), CDVA (0.39 ± 0.26-0.17 ± 0.15, P < 0.01), cylinder (-4.97 ± 2.68 to -1.74 ± 1.25, P < 0.01), steep keratometry (51.25 ± 3.37-45.03 ± 2.27, P < 0.01), central keratometry (52.59 ± 4.98-46.99 ± 3.53, P < 0.01), and maximum keratometry (58.78 ± 4.22-50.76 ± 3.42, P < 0.01). These results were sustained at 48-month follow-up. CCT decreased at 12 months after TGPRK (461.84 ± 27.46-418.94 ± 45.62, P < 0.01) and remained stable at 60 months. Postoperatively, 2 eyes (3.51%) had corneal haze, resulting in decrease in CDVA; 1 was treated successfully with repeat PRK; and 1 patient (1.75%) had wound melt due to partial Keraring extrusion, which settled with repositioning. CONCLUSIONS: Keraring implantation followed by simultaneous TGPRK and CXL appears to be effective in the long term in improving UDVA, CDVA, cylinder, CCT, and keratometry in patients with keratoconus who are intolerant to contact lenses.

Impact of Type 2 diabetes mellitus and insulin use on progression to glaucoma surgery in primary open angle glaucoma.

PURPOSE: To investigate outcomes of primary open-angle glaucoma (POAG) patients with and without type 2 diabetes mellitus (T2DM). METHODS: Retrospective observational study using U.S. nationwide healthcare insurance claims database. Patients ≥40 years old with at least one HbA1c within one year of POAG diagnosis were included. Diabetic factors associated with POAG progression requiring glaucoma surgery were evaluated using multivariable Cox proportional hazards regression models adjusted for demographic, diabetic and glaucoma factors. T2DM diagnosis and use of either oral hypoglycaemic agents or insulin therapy were assessed in association with POAG progression requiring glaucoma surgery. RESULTS: 104,515 POAG patients were included, of which 70,315 (67%) had T2DM. The mean age was 68.9 years (Standard deviation 9.2) and 55% were female. Of those with T2DM, 93% were taking medication (65,468); 95% (62,412) taking oral hypoglycaemic agents, and 34% (22,028) were on insulin. In multivariable analyses, patients with T2DM had a higher hazard of requiring glaucoma surgery (Hazard ratio, HR 1.15, 95% CI 1.09-1.21, p < 0.001). Higher mean HbA1c was also a significant predictor of progression requiring glaucoma surgery (HR 1.02, 95% CI 1.01-1.03, p < 0.001). When evaluating only patients who were taking antidiabetic medication, after adjusting for confounders, insulin use was associated with a 1.20 higher hazard of requiring glaucoma surgery compared to oral hypoglycaemic agents (95% CI 1.14-1.27, p < 0.001), but when stratified by HbA1c, this effect was only significant for those with HbA1c > 7.5%. CONCLUSIONS: Higher baseline HbA1c, particularly in patients taking insulin may be associated with higher rates of glaucoma surgery in POAG.

A case study in applying artificial intelligence-based named entity recognition to develop an automated ophthalmic disease registry.

PURPOSE: Advances in artificial intelligence (AI)-based named entity extraction (NER) have improved the ability to extract diagnostic entities from unstructured, narrative, free-text data in electronic health records. However, there is a lack of ready-to-use tools and workflows to encourage the use among clinicians who often lack experience and training in AI. We sought to demonstrate a case study for developing an automated registry of ophthalmic diseases accompanied by a ready-to-use low-code tool for clinicians. METHODS: We extracted deidentified electronic clinical records from a single centre's adult outpatient ophthalmology clinic from November 2019 to May 2022. We used a low-code annotation software tool (Prodigy) to annotate diagnoses and train a bespoke spaCy NER model to extract diagnoses and create an ophthalmic disease registry. RESULTS: A total of 123,194 diagnostic entities were extracted from 33,455 clinical records. After decapitalisation and removal of non-alphanumeric characters, there were 5070 distinct extracted diagnostic entities. The NER model achieved a precision of 0.8157, recall of 0.8099, and F score of 0.8128. CONCLUSION: We presented a case study using low-code artificial intelligence-based NLP tools to produce an automated ophthalmic disease registry. The workflow created a NER model with a moderate overall ability to extract diagnoses from free-text electronic clinical records. We have produced a ready-to-use tool for clinicians to implement this low-code workflow in their institutions and encourage the uptake of artificial intelligence methods for case finding in electronic health records.

Detection of systemic cardiovascular illnesses and cardiometabolic risk factors with machine learning and optical coherence tomography angiography: a pilot study.

BACKGROUND/OBJECTIVES: Optical coherence tomography angiography (OCTA) has been found to identify changes in the retinal microvasculature of people with various cardiometabolic factors. Machine learning has previously been applied within ophthalmic imaging but has not yet been applied to these risk factors. The study aims to assess the feasibility of predicting the presence or absence of cardiovascular conditions and their associated risk factors using machine learning and OCTA. METHODS: Cross-sectional study. Demographic and co-morbidity data was collected for each participant undergoing 3 × 3 mm, 6 × 6 mm and 8 × 8 mm OCTA scanning using the Carl Zeiss CIRRUS HD-OCT model 5000. The data was then pre-processed and randomly split into training and testing datasets (75%/25% split) before being applied to two models (Convolutional Neural Network and MoblieNetV2). Once developed on the training dataset, their performance was assessed on the unseen test dataset. RESULTS: Two hundred forty-seven participants were included. Both models performed best in predicting the presence of hyperlipidaemia in 3 × 3 mm scans with an AUC of 0.74 and 0.81, and accuracy of 0.79 for CNN and MobileNetV2 respectively. Modest performance was achieved in the identification of diabetes mellitus, hypertension and congestive heart failure in 3 × 3 mm scans (all with AUC and accuracy >0.5). There was no significant recognition for 6 × 6 and 8 × 8 mm for any cardiometabolic risk factor. CONCLUSION: This study demonstrates the strength of ML to identify the presence cardiometabolic factors, in particular hyperlipidaemia, in high-resolution 3 × 3 mm OCTA scans. Early detection of risk factors prior to a clinically significant event, will assist in preventing adverse outcomes for people.

Glaucoma and Myopia: Diagnostic Challenges.

The rising global prevalence of myopia is a growing concern for clinicians, as it predisposes patients to severe ocular pathologies including glaucoma. High myopia can be associated with clinical features that resemble glaucomatous damage, which make an accurate glaucoma diagnosis challenging, particularly among patients with normal intraocular pressures. These patients may also present with established visual field defects which can mimic glaucoma, and standard imaging technology is less useful in disease detection and monitoring due to the lack of normative data for these anatomically unique eyes. Progression over time remains the most critical factor in facilitating the detection of early glaucomatous changes, and thus careful longitudinal follow-up of high-risk myopic patients is the most important aspect of management. Here, we review our current understanding of the complex relationship between myopia and glaucoma, and the diagnostic challenges and limitations of current testing protocols including visual field, intraocular pressure, and imaging. Furthermore, we discuss the clinical findings of two highly myopic patients with suspected glaucoma.

Establishing human lacrimal gland cultures from biopsy-sized tissue specimens.

OBJECTIVES: To establish cultures of human lacrimal gland from patient-derived, biopsy-sized, tissue specimens. METHODS: Tissue was obtained after surgical removal from patients without dry eye disease undergoing routine procedures. Samples were subjected to mechanical and enzymatic digestion and resulting cell suspensions were plated onto collagen-coated glass coverslips and grown for up to 21 days. Cultures were analysed by immunocytochemistry and light microscopy, and resultant cellular distributions were compared to those in sections of fixed human lacrimal gland tissue. RESULTS: Dissociation of biopsy-sized pieces of human lacrimal gland and seeding onto coated surfaces allowed development of a mixed population of cells in vitro. Within 7-14 days, cellular aggregation was observed and by 21 days many cells had organised themselves into distinct three-dimensional complexes. Immunohistochemistry revealed a heterogeneous population of cells, including epithelial, myoepithelial, mesenchymal and progenitor cells. Some of the epithelia labelled positively for lysozyme and lactoferrin. CONCLUSIONS: Collection and dissociation of biopsy-sized pieces of human lacrimal gland leads to a cellular preparation that can proliferate in vitro and organise into three-dimensional structures. This is the first report detailing that biopsy-collected specimens of human lacrimal gland can be used to establish cell cultures.

Changes in glaucoma management following visual field testing and optical coherence tomography.

BACKGROUND: Optimal utilisation of investigations in glaucoma management remains unclear. We aimed to assess whether a temporal association exists between such testing and management changes. METHODS: Retrospective observational study using nationwide healthcare insurance claims database. Glaucoma outpatient encounters from patients aged ≥40 years with/without Humphrey visual field (HVF) and/or optical coherence tomography (OCT) were identified. An encounter was considered associated with an intervention if surgery occurred within 90 days, or if medication change or laser trabeculoplasty (LT) occurred within 30 days. RESULTS: 12 669 324 outpatient encounters of 1 863 748 individuals from 2003 to 2020 were included. HVF and OCT was performed during 32.8% and 22.2% of encounters respectively. Of the 36 763 (0.3%) encounters preceding surgery, 28.1% included HVF, 11.9% had OCT and 8.5% both. 79 181 (0.6%) visits preceded LT, of which 28.2% had HVF, 13.2% OCT and 9.3% both. Of the 515 899 (4.5%) encounters preceding medication changes, 29.1% had HVF, 16.7% OCT and 12.2% both. Compared with encounters with no investigations, those with HVF and/or OCT were associated with a 49% increased odds of a management change (p<0.001). In multivariate analyses, compared with encounters without investigations, visits with HVF alone had higher odds of subsequent surgery and LT, while HVF and/or OCT were associated with higher odds of medication change (p<0.001 for all). CONCLUSION: Glaucoma therapeutic changes occurred following approximately 5% of outpatient encounters. Surgery and LT were more likely to occur following a visit with a HVF rather than an OCT, while either investigation was associated with a higher odds of medication change.

Nationwide Trends in Vitreoretinal Procedures within Australia.

PURPOSE: To investigate Australian age stratified nationwide trends in vitreoretinal procedures. METHODS: Nationwide retrospective analysis of vitreoretinal procedures in Australia over 2001-2019 using Australian National Hospital Morbidity Database for public and private hospitals. Age and gender-specific trends in selected procedures including pars plana vitrectomy for retinal detachment (PPV for RD), scleral buckle, intravitreal injections, and PPV unrelated to RD were analysed using negative binomial regression. RESULTS: Total included procedures increased from 8102 in 2001 to 136430 in 2019. Between 2001 and 2019, the incidence per 100,000 persons of PPV for RD increased from 7.5 to 20.7, whilst scleral buckling decreased from 10.5 to 4.0. Similarly, the incidence per 100,000 persons of PPV unrelated to RD increased from 18.4 to 67.1, and intravitreal injections increased from 5.6 to 446.0. The rate of scleral buckling decreased by 6% annually (p < .001), most pronounced in those 40 years and above. In contrast, PPV for RD increased by 5% annually (p < .001), also most pronounced in those aged 40 and above. PPV unrelated to RD increased by 7% annually (p < .001), and intravitreal injections increased by 21.0% annually (p < .001). CONCLUSION: Between 2001 and 2019, the rate of scleral buckling declined compared to an increase in PPV for RD. Our analysis suggests an increasing trend to PPV over scleral buckling for RD repair in Australia over the last two decades. Additionally, rates of PPV unrelated to RD and intravitreal injections increased across all age groups. Overall, these trends mirror those seen internationally and reflect changing practice patterns over time.

Blood Pressure Measures and Incident Primary Open-Angle Glaucoma.

Purpose: To investigate the association of systemic blood pressure and incident primary open-angle glaucoma (POAG) using a large open-access database. Methods: Prospective cohort study included 484,268 participants from the UK Biobank without glaucoma at enrollment. Incident POAG events were recorded through assessment visits, hospital inpatient admissions, and primary care data. Blood pressure measures included systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP). Repeated measurements throughout the study period were analyzed as time-varying covariables. The parameters were modeled as both categorical and continuous nonlinear variables. The primary outcome measure was the relative hazard of incident POAG. Results: There were 2390 incident POAG events over 5,715,480 person-years of follow-up. Median follow-up was 12.08 years. In multivariable analyses, compared to SBP and PP in the normal range (SBP, 120-130 mmHg; PP, 40-50 mmHg), higher SBP and PP were associated with an increased risk of incident POAG (linear trend P = 0.038 for SBP, P < 0.001 for PP). Specifically, SBP of 130 to 140 mmHg or 140 to 150 mmHg was associated with a 1.16 higher hazard of incident POAG (95% CI, 1.01-1.32 and 1.01-1.33, respectively), whereas a PP of greater than 70 mmHg was associated with a 1.13 higher hazard of incident glaucoma (95% CI, 1.00-1.29). In multivariable models, no statistically significant associations were found for DBP or MAP with incident glaucoma. These findings were similar when blood pressure measures were modeled as continuous variables. Conclusions: Higher SBP and PP were associated with an increased risk of incident POAG. Further studies are required to characterize these relationships better.

Real-World Outcomes of Glaucoma Filtration Surgery Using Electronic Health Records: An Informatics Study.

PRCIS: Utilizing an automated pipeline for data extraction from electronic health records provides real-world information on the success of various glaucoma procedures, with tube shunt implantation associated with increased failure rates compared with trabeculectomy. BACKGROUND: We aimed to evaluate the long-term survival of glaucoma surgeries using an automated pipeline for extraction of outcomes from electronic health records. METHODS: A retrospective observational study from a single academic center. Patients undergoing trabeculectomy, Ex-PRESS shunt, Baerveldt, and Ahmed tube shunt insertion from 2009 to 2018 were identified from electronic health record procedure codes. Patient characteristics were identified from structured and unstructured fields using a previously validated natural language processing pipeline. RESULTS: Five hundred twelve patients underwent 711 glaucoma surgeries: 287 trabeculectomies, 47 Ex-PRESS shunts, 274 Baerveldt and 103 Ahmed tube implantations. The Median follow-up was 359 days. The mean baseline IOP was 24.4 mm Hg (SD 10.9), and 73.1% were on ≥3 medications. Compared with trabeculectomy, tube shunt surgery had a higher risk of failure (Baerveldt: Hazard Ratio (HR) 1.44, 95% CI 1.02 to 2.02; Ahmed: HR 2.01, 95% CI 1.28 to 3.17). Previous glaucoma surgery was associated with increased failure (≥2 previous surgeries: HR 2.74, 95% CI 1.62 to 4.64), as were fewer baseline medications (<3 medications: HR 2.96, 95% CI 2.12 to 4.13) and male sex (HR 1.40, 95% CI 1.03 to 1.90). At 1 year, tube shunt patients had a 2.53 mm Hg ( P =0.002) higher IOP compared with trabeculectomy patients. CONCLUSIONS: Baerveldt and Ahmed tube shunt implantation was associated with increased failure compared with trabeculectomy. Fewer baseline medications, previous glaucoma surgeries, and male sex were also risk factors for failure. These results demonstrate the utility of applying an informatics pipeline to electronic health records to investigate key clinical questions using real-world evidence.

Structural and Metabolic Imaging After Short-term Use of the Balance Goggles System in Glaucoma Patients: A Pilot Study.

PRCIS: Short-term use of the Balance Goggles System (BGS) in glaucoma patients was not associated with the observable changes in conventional ocular coherence tomography (OCT) imaging, but metabolic imaging using peripapillary flavoprotein fluorescence (FPF) may represent a useful adjuctive investigation. OBJECTIVE: To determine whether the intraocular pressure (IOP)-lowering effects of the BGS are accompanied by changes in retinal thickness measured by OCT, retinal vascular density measured by ocular coherence tomography-angiography (OCTA), or novel peripapillary metabolic profiling using FPF measured by a fundus camera. DESIGN: Prospective comparative case-series. SUBJECTS: Eight eyes from 8 patients with open angle glaucoma ranging from mild to severe. METHODS: In this prospective, single-center, open-label, nonrandomized, and single-arm study patients received a baseline evaluation including retinal imaging, then 1 hour of negative pressure application through the BGS, followed by repeat retinal imaging. Participants then used the BGS at home for 1 month and underwent a repeat evaluation at the conclusion of the trial. MAIN OUTCOME MEASURES: Changes in nerve fiber layer thickness, OCTA vascular parameters, and FPF scores. RESULTS: Mean baseline IOP was 18.0±3.1 mmHg and there was no significant change in IOP at follow-up. At 1 month compared with baseline, there was a statistically significant improvement in FPF optic nerve head rim scores (12.7±11.6 to 10.5±7.5; P =0.04). In addition, there was a trend toward an increase in retinal nerve fiber layer thickness after 1 month (69.5±14.2 to 72.0±13.7; P =0.1), but there were no statistically significant differences observable with any of the OCTA vascular parameters either at 1 hour or after 1 month. CONCLUSIONS: There were no significant changes observable using conventional OCT imaging after short-term use of the BGS, although metabolic imaging using FPF may be a useful potential biomarker to complement existing investigations. Additional studies are warranted to further investigate these changes.

Changing trends in glaucoma surgery within Australia.

BACKGROUND: Limited data are available on glaucoma surgical trends in Australia. METHODS: Nationwide study of glaucoma surgery in Australia over 17-year period from 2001 to 2018. The Australian Institute of Health, Welfare and Ageing hospitalisation database was used to review age- and gender-specific trends in glaucoma surgeries from 2001 to 2018 in Australian public and private hospitals. RESULTS: Although there was an increase in the absolute number of trabeculectomy procedures from 2926 to 3244 over the 17-year study period, this represented a decline in the age-standardised and gender-standardised number of trabeculectomy procedures from 15.1 to 13.2 procedures per 100 000 persons. However, during this same period, there was a dramatic increase in the number of glaucoma drainage devices (GDD) from 119 to 3262 procedures, representing an age-standardised and gender-standardised increase from 0.6 to 13.3 procedures per 100 000 persons. Negative binomial regression analysis revealed a decrease in trabeculectomy procedures of 1.1% per year, while there was increase in GDD insertions of 16.3% per year (p<0.001 for both). When stratified by age group, there was a statistically significant interaction in both trabeculectomy and GDD rates by age groups over time (p<0.001 for both). Trabeculectomy procedures decreased to a greater extent in those aged >60 years, compared with stable or increasing rates in younger age groups. GDD insertion rates demonstrated a progressively greater increase in older compared with younger age groups. CONCLUSION: Our findings demonstrate changing trends in the surgical management of advanced glaucoma in Australia, likely reflecting updated evidence regarding the role of GDD surgeries.

A survey of visual impairment and blindness in children attending eight schools for the blind in Myanmar: An update.

Purpose: To determine the causes of visual impairment (VI) and blindness among children in schools for the blind in Myanmar; to identify the avoidable causes of VI and blindness; to provide spectacles, low-vision aids, and ophthalmic treatment where indicated; to provide an update of the 2007 survey performed and identify any major epidemiological changes. Methods: Two hundred and ninety children under 16 years of age from all eight schools for the blind in Myanmar were examined and the data entered into the World Health Organization Prevention of Blindness Examination Record for Childhood Blindness. Results: In total, 271 children (93.4%) were blind (visual acuity [VA] <3/60 in the better eye) and 15 (5.17%) had severe visual impairment (SVI = VA <6/60 to 3/60 in the better eye). Most children had whole globe as the major anatomical site of SVI or blindness (105, 36.6%). The cause was unknown in the majority of these (155, 54.0%). One hundred and twelve children had avoidable causes of blindness and SVI (39.0%). Forty children (13.9%) required an optical device and 10.1% required surgical or medical attention, with a potential for visual improvement through intervention in 3.48%. Conclusion: In all, 39.0% of children had potentially avoidable causes of SVI and blindness with cataracts and measles being the commonest causes. This follow-up survey performed after the first one completed in Myanmar in 2007 demonstrates a change in the major site of abnormality from the cornea to whole globe and a reduction in avoidable blindness but highlights the ongoing burden of measles.

Anti-VEGF crunch syndrome in proliferative diabetic retinopathy: A review.

Anti-vascular endothelial growth factor (anti-VEGF) crunch syndrome describes the progression to tractional retinal detachment following intravitreal anti-VEGF therapy in an eye with proliferative diabetic retinopathy . We reviewed the literature on the anti-VEGF crunch using the PubMed and Cochrane databases. Anti-VEGF crunch typically manifests as sudden vision loss in the affected eye between 1 and 6 weeks following intravitreal anti-VEGF injection, with a mean onset of 13 days. Risk factors for crunch development include the use of a higher anti-VEGF dose and increased severity of diabetic retinopathy with fibrosis. Our review found that intravitreal anti-VEGF, in particular bevacizumab, should be used with caution when treating patients with severe proliferative diabetic retinopathy and pre-existing intraocular fibrosis. In patients where anti-VEGF is used before a planned vitrectomy, we recommend close monitoring for crunch symptoms and proceeding promptly with surgery if there is new or progression of tractional retinal detachment. For eyes with minimal preexisting traction that develop crunch after anti-VEGF treatment, surgeons should proceed to vitrectomy within 7 days. The existing literature on the anti-VEGF crunch is limited by heterogeneity in the way crunch is documented and characterized and the presence of panretinal photocoagulation as a confounding factor. Because of these methodological flaws, the relative frequency of the anti-VEGF crunch cannot be accurately estimated.

Impact of cardiometabolic factors on retinal vasculature: A 3 × 3, 6 × 6 and 8 × 8-mm ocular coherence tomography angiography study.

BACKGROUND: Ocular coherence tomography angiography (OCTA) is available in varying size and resolution. We sought to characterise associations of cardiometabolic factors with retinal microvascular changes using 3 × 3, 6 × 6 and 8 × 8-mm OCTA scans to determine differences in detection with varying scan size. METHODS: Cross-sectional study of 247 cardiovascular patients from a single-centre tertiary-care hospital. Demographic, comorbidity and medication data were obtained. Patients underwent 3 × 3, 6 × 6 and 8 × 8-mm macula OCTA scanning using Carl Zeiss CIRRUS HD-OCT Model 5000. Angioplex and AngioTool software was used to quantify vascular parameters in the superficial capillary plexus. RESULTS: Increasing age, hypertension, dyslipidaemia, diabetes, chronic kidney disease, coronary artery disease and peripheral vascular disease were associated with reductions in vessel density, vessel perfusion, average vessel length and/or junction density in 3 × 3-mm OCTA (P < .05 for all). Conversely, smoking was associated with increased vessel density, vessel length and junction density in 3 × 3-mm OCTA (P < .05 for all). Associations of vessel abnormalities with cardiometabolic factors were progressively weakened and statistically attenuated in 6 × 6 and 8 × 8-mm OCTA scans. In multivariate analyses, dyslipidaemia remained an independent predictor of reduced vessel density, average vessel length and junction density (P < .05). CONCLUSIONS: Cardiometabolic factors are associated with multiple retinal microvascular changes in 3 × 3-mm OCTA scans. These associations were weakened and progressively attenuated in OCTA scans of larger 6 × 6 and 8 × 8-mm size. These findings advance our understanding of microcirculatory dysfunction and may have future implications for the screening and management of patients with cardiometabolic risk factors. Additional studies are required to further investigate these important associations.

Meta-Analysis of Intraocular Bleeding With Dual Antiplatelet Therapy Using P2Y12 Inhibitors Prasugrel or Ticagrelor.

Intraocular bleeding is a devastating clinical event due to its potentially blinding nature. It is not known if determine if dual antiplatelet therapy using aspirin and potent P2Y12 inhibitors increases this risk. We searched MEDLINE and ClinicalTrials.gov for randomized controlled trials that were phase III, randomly assigned patients to dual antiplatelet therapy with either aspirin and a potent P2Y12 inhibitor or aspirin and clopidogrel, had follow-up of 6 months, and at least 200 patients. Corresponding authors were contacted for intraocular bleeding data. Inverse-variance, weighted, fixed-effects meta-analysis was undertaken, with random-effects meta-analysis performed as a sensitivity analysis. Four trials enrolling 42,850 patients were included. The median follow-up ranged from 12 to 14 months. There was overall low risk of bias. Pooled analysis demonstrated no statistically significant increase in the risk of intraocular bleeding with dual antiplatelet therapy using potent P2Y12 inhibitors compared with clopidogrel (risk ratio 0.89, 95% confidence interval 0.58 to 1.36). There was no significant heterogeneity observed across trials (I2 statistic 0%, p = 0.98). The use of random-effects meta-analysis did not change the effect estimate or confidence intervals, and the results appeared similar when stratified by potent P2Y12 inhibitor (p = 0.97). In conclusion, this collaborative meta-analysis of dual antiplatelet trials does not suggest that the risk of intraocular bleeding is increased with the use of potent P2Y12 inhibitors compared with clopidogrel. Our results suggest that these potent P2Y12 inhibitors may continue to be used cautiously where indicated as part of dual antiplatelet therapy, even in those at high risk of spontaneous intraocular bleeding.

Development of Macroporous Chitosan Scaffolds for Eyelid Tarsus Tissue Engineering.

Background: Reconstruction of large eyelid defects remains challenging due to the lack of suitable eyelid tarsus tissue substitutes. We aimed to evaluate a novel bioengineered chitosan scaffold for use as an eyelid tarsus substitute. Methods: Three-dimensional macroporous chitosan hydrogel scaffold were produced via cryogelation with specific biomechanical properties designed to directly match characteristics of native eyelid tarsus tissue. Scaffolds were characterized by confocal microscopy and tensile mechanical testing. To optimise biocompatibility, human eyelid skin fibroblasts were cultured from biopsy-sized samples of fresh eyelid skin. Immunological and gene expression analysis including specific fibroblast-specific markers were used to determine the rate of fibroblast de-differentiation in vitro and characterize cells cultured. Eyelid skin fibroblasts were then cultured over the chitosan scaffolds and the resultant adhesion and growth of cells were characterized using immunocytochemical staining. Results: The chitosan scaffolds were shown to support the attachment and proliferation of NIH 3T3 mouse fibroblasts and human orbital skin fibroblasts in vitro. Our novel bioengineered chitosan scaffold has demonstrated biomechanical compatibility and has the ability to support human eyelid skin fibroblast growth and proliferation. Conclusions: This bioengineered tissue has the potential to be used as a tarsus substitute during eyelid reconstruction, offering the opportunity to pre-seed the patient's own cells and represents a truly personalised approach to tissue engineering.