En kvinne i 60-årene som ikke lenger gjenkjente det hun så.

BACKGROUND: Neurological disorders can present with a vast array of visual disturbances. The constellation of symptoms and findings in this patient prompted workup for unusual causes of both stroke and neurodegenerative disorder. CASE PRESENTATION: A woman in her sixties presented with visual disturbances, followed by weakness in her right arm and aphasia three days later. Her close acquaintances had suspected progressive cognitive decline during the previous year. CT and MRI showed an occluded left posterior cerebral artery with a subacute occipito-temporal infarction. The finding of extensive white matter lesions and segmental arterial vasoconstriction necessitated further workup of vasculitis and hereditary small vessel disease, which were ruled out. The stroke aetiology was considered to be atherosclerotic intracranial large vessel disease. FDG-PET scan revealed decreased metabolism in the left hemisphere, and cerebrospinal biomarkers had slightly decreased beta-amyloid. The findings were suggestive of early Alzheimer's disease or primary progressive aphasia, but currently inconclusive. INTERPRETATION: Based on clinical-anatomical correlation, the patient's visual disturbances, in this case right hemianopsia and object agnosia, were solely related to the stroke and not to a neurodegenerative disorder. Knowledge and interpretation of visual agnosias can in many cases be clinically valuable.

Human ocular surface microcirculation quantified by in vivo computer assisted video microscopy and diffuse reflectance spectroscopy.

Non-invasive imaging techniques are increasingly used to objectively quantify anterior segment structures of the eye. In this study, we apply the novel oxygen delivery index (ODIN) concept that, quantifies microvascular capacity for oxygen delivery, to the ocular surface in healthy humans. The purpose of the study was to test the applicability of the technologies used for data acquisition from the human ocular surface. We also validated whether the ODIN concept has sufficient sensitivity to detect and differentiate between microvascular structure and function in limbal and bulbar conjunctiva. Multiple ocular surface measurements using computer-assisted video microscopy (field of view: 1.6 mm × 0.9 mm) and diffuse reflectance spectroscopy (measuring volume: ∼0.1 mm3) were obtained from limbal and bulbar conjunctiva in 20 healthy volunteers. Three parameters were extracted during analyses: Functional capillary density, capillary flow velocity, and microvascular oxygen saturation. Functional capillary density was higher at limbus than in bulbar conjunctiva (11.2 ± 1.8 c/mm versus 5.2 ± 1.2 c/mm, p < 0.01), and microvascular oxygen saturation was lower at limbus (77 ± 8%) as compared to bulbar conjunctiva (89 ± 6%), p < 0.01. More than 80% of scored capillaries had continuous blood flow and no difference was seen between the recording sites (p = 0.68). In conclusion, the ODIN concept is applicable for the assessment of human ocular surface microvascular function and has sufficient sensitivity to detect increased capillary density and oxygen extraction at limbus as compared with bulbar conjunctiva.

Ocular surface microcirculation is better preserved with pulsatile versus continuous flow during cardiopulmonary bypass-An experimental pilot.

BACKGROUND: Non-pulsatile cardiopulmonary bypass (CPB) may induce microvascular dysregulation. In piglets, we compared ocular surface microcirculation during pulsatile versus continuous flow (CF) bypass. METHODS: Ocular surface microcirculation in small tissue volumes (~0.1 mm3 ) at limbus (high metabolic rate) and bulbar conjunctiva (low metabolic rate) was examined in a porcine model using computer assisted video microscopy and diffuse reflectance spectroscopy, before and after 3 and 6 h of pulsatile (n = 5 piglets) or CF (n = 3 piglets) CPB. Functional capillary density, capillary flow velocity and microvascular oxygen saturation were quantified. RESULTS: At limbus, velocities improved with pulsatility (p < 0.01) and deteriorated with CF (p < 0.01). In bulbar conjunctiva, velocities were severely reduced with CF (p < 0.01), accompanied by an increase in capillary density (p < 0.01). Microvascular oxygen saturation decreased in both groups. CONCLUSION: Ocular surface capillary densities and flow patterns are better preserved with pulsatile versus CF during 6 h of CPB in sleeping piglets.

The Value of Macular Optical Coherence Tomography in Watchful Waiting of Suprasellar Masses: A 2-Year Observational Study.

BACKGROUND: A possible benefit of optical coherence tomography (OCT) in the approach to tumors involving the optic chiasm may be the ability to foresee visual deterioration. This study investigated the value of OCT in watchful waiting for compressive optic neuropathy as the primary management of suprasellar masses. METHODS: The research was conducted as a 2-year observational study of a patient cohort with conservatively managed mass lesions involving the optic chiasm on MRI. Threshold perimetry and macular OCT were performed at baseline and each follow-up examination. Univariate Cox regression was used to determine the effect of baseline and longitudinal covariates upon development of visual field (VF) loss compatible with chiasmal dysfunction. RESULTS: Nineteen eyes of 19 patients were included. The optic chiasm-tumor relationship on baseline MRI was abutment in 6 cases and compression in 13 cases. Seven eyes developed VF loss. None of the baseline covariates were predictors of VF loss. The longitudinal decrease in mean macular ganglion cell complex (mGCC) thickness on OCT was 2.5 µm/yr for eyes that developed VF loss and 0.2 µm/yr for eyes that did not develop VF loss (P = 0.02). The hazard ratio for VF loss per 1-µm/yr decrease in mGCC thickness was 1.30 (95% confidence interval [CI] 1.04-1.62; P = 0.02) for the inferior nasal quadrant and 1.45 (95% CI 1.02-2.07; P = 0.04) for the inferior temporal quadrant. CONCLUSIONS: OCT offers a valuable complement to perimetry in monitoring for compressive optic neuropathy. Longitudinal mGCC thinning can anticipate VF loss.

Quantification of ocular surface microcirculation by computer assisted video microscopy and diffuse reflectance spectroscopy.

In piglets we tested the applicability of digital video microscopy and diffuse reflectance spectroscopy for non-invasive assessments of limbal and bulbar conjunctival microcirculation. A priori we postulated that the metabolic rate is higher in limbal as compared to bulbar conjunctiva, and that this difference is reflected in microvascular structure or function between the two locations. Two study sites, Oslo University Hospital (OUH), Norway and Cleveland Clinic (CC), USA, used the same video microscopy and spectroscopy techniques to record limbal and bulbar microcirculation in sleeping piglets. Recordings were analyzed with custom-made software to quantify functional capillary density, capillary flow velocity and microvascular oxygen saturation in measuring volumes of approximately 0.1 mm3. The functional capillary density was higher in limbus than in bulbar conjunctiva at both study sites (OUH: 18.1 ± 2.9 versus 12.2 ± 2.9 crossings per mm line, p < 0.01; CC: 11.3 ± 3.0 versus 7.1 ± 2.8 crossings per mm line, p < 0.01). Median categorial capillary blood flow velocity was higher in bulbar as compared with limbal recordings (CC: 3 (1-3) versus 1 (0-3), p < 0.01). Conjunctival microvascular oxygen saturation was 88 ± 5.9% in OUH versus 94 ± 7.5% in CC piglets. Non-invasive digital video microscopy and diffuse reflectance spectroscopy can be used to obtain data from conjunctival microcirculation in piglets. Limbal conjunctival microcirculation has a larger capacity for oxygen delivery as compared with bulbar conjunctiva.

A proof-of-concept study of a prototype needle that mitigates intraocular pressure rise following intravitreal injection.

PURPOSE: To determine the feasibility of a prototype needle that enhances vitreous reflux (VR) to control intraocular pressure (IOP) in intravitreal injection (IVI). METHODS: We created an eye model to compare IVI using a standard 30-G needle with four different versions of a 30-G prototype needle with one to four surface grooves that enhanced VR. We injected 50, 70, and 100 µl saline through porcine sclera or 460-µm-thick rubber and measured the peak and 3-second pressure before we extracted the needle and measured the 10-second pressure. RESULTS: 50-µl injection through sclera with the standard needle resulted in mean (SD) pressure of 58.6 (3.8) mmHg at peak, 52.8 (4.7) mmHg at 3 s, and 39.6 (18.0) mmHg at 10 s. The prototype needle lowered the pressure; four grooves resulted in mean (SD) pressure of 29.4 (5.6) mmHg at peak, 22.0 (3.7) mmHg at 3 s, and 7.2 (6.6) mmHg at 10 s. 70-µl and 100-µl injections through sclera with the standard needle resulted in mean (SD) pressure of 68.8 (3.6) and 86.0 (6.0) mmHg at peak. Similar to 50-µl injection, the prototype needle lowered the pressure for 70-µl and 100-µl injections. At 10 s, we observed varying leakage at the injection site for sclera but not for rubber. CONCLUSIONS: The study provides proof of concept for a needle design for which surface grooves enhance VR and counteract the effect of IVI on IOP. The safety and efficacy of the prototype needle must be studied further in a clinical trial.

A health economic pilot study comparing two diabetic retinopathy screening strategies.

To compare two screening strategies for diabetic retinopathy (DR), and to determine the health-economic impact of including optical coherence tomography (OCT) in a regular DR screening. This cross-sectional study included a cohort of patients (≥ 18 years) with type 1 or 2 diabetes mellitus (T1D or T2D) from a pilot DR screening program at Oslo University Hospital, Norway. A combined screening strategy where OCT was performed in addition to fundus photography for all patients, was conducted on this cohort and compared to our existing sequential screening strategy. In the sequential screening strategy, OCT was performed on a separate day only if fundus photography indicated diabetic macular edema (DME). The presence of diabetic maculopathy on fundus photography and DME on OCT was determined by two medical retina specialists. Based on the prevalence rate of diabetic maculopathy and DME from the pilot, we determined the health-economic impact of the two screening strategies. The study included 180 eyes of 90 patients. Twenty-seven eyes of 18 patients had diabetic maculopathy, and of these, 7 eyes of 6 patients revealed DME on OCT. When diabetic maculopathy was absent on fundus photographs, OCT could not reveal DME. Accordingly, 18 patients (20%) with diabetic maculopathy would have needed an additional examination with OCT in the sequential screening strategy, 6 (33%) of whom would have had DME on OCT. In an extended healthcare perspective analysis, the cost of the sequential screening strategy was higher than the cost of the combined screening strategy. There was a weak association between diabetic maculopathy on fundus photography and DME on OCT. The health economic analysis suggests that including OCT as a standard test in DR screening could potentially be cost-saving.

Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma.

BACKGROUND: The growth and recurrence of several cancers appear to be driven by a population of cancer stem cells (CSCs). Glioblastoma, the most common primary brain tumor, is invariably fatal, with a median survival of approximately 1 year. Although experimental data have suggested the importance of CSCs, few data exist regarding the potential relevance and importance of these cells in a clinical setting. METHODS: We here present the first seven patients treated with a dendritic cell (DC)-based vaccine targeting CSCs in a solid tumor. Brain tumor biopsies were dissociated into single-cell suspensions, and autologous CSCs were expanded in vitro as tumorspheres. From these, CSC-mRNA was amplified and transfected into monocyte-derived autologous DCs. The DCs were aliquoted to 9-18 vaccines containing 10(7) cells each. These vaccines were injected intradermally at specified intervals after the patients had received a standard 6-week course of post-operative radio-chemotherapy. The study was registered with the ClinicalTrials.gov identifier NCT00846456. RESULTS: Autologous CSC cultures were established from ten out of eleven tumors. High-quality RNA was isolated, and mRNA was amplified in all cases. Seven patients were able to be weaned from corticosteroids to receive DC immunotherapy. An immune response induced by vaccination was identified in all seven patients. No patients developed adverse autoimmune events or other side effects. Compared to matched controls, progression-free survival was 2.9 times longer in vaccinated patients (median 694 vs. 236 days, p = 0.0018, log-rank test). CONCLUSION: These findings suggest that vaccination against glioblastoma stem cells is safe, well-tolerated, and may prolong progression-free survival.

Wnt/ß-Catenin Signaling Activation Induces Differentiation in Human Limbal Epithelial Stem Cells Cultured Ex Vivo.

Human limbal epithelial stem cells (hLESCs) continuously replenish lost or damaged human corneal epithelial cells. The percentage of stem/progenitor cells in autologous ex vivo expanded tissue is essential for the long-term success of transplantation in patients with limbal epithelial stem cell deficiency. However, the molecular processes governing the stemness and differentiation state of hLESCs remain uncertain. Therefore, we sought to explore the impact of canonical Wnt/ß-catenin signaling activation on hLESCs by treating ex vivo expanded hLESC cultures with GSK-3 inhibitor LY2090314. Real-time qRT-PCR and microarray data reveal the downregulation of stemness (TP63), progenitor (SOX9), quiescence (CEBPD), and proliferation (MKI67, PCNA) genes and the upregulation of genes for differentiation (CX43, KRT3) in treated- compared to non-treated samples. The pathway activation was shown by AXIN2 upregulation and enhanced levels of accumulated ß-catenin. Immunocytochemistry and Western blot confirmed the findings for most of the above-mentioned markers. The Wnt/ß-catenin signaling profile demonstrated an upregulation of WNT1, WNT3, WNT5A, WNT6, and WNT11 gene expression and a downregulation for WNT7A and DKK1 in the treated samples. No significant differences were found for WNT2, WNT16B, WIF1, and DKK2 gene expression. Overall, our results demonstrate that activation of Wnt/ß-catenin signaling in ex vivo expanded hLESCs governs the cells towards differentiation and reduces proliferation and stem cell maintenance capability.

A Novel Technique of Amniotic Membrane Preparation Mimicking Limbal Epithelial Crypts Enhances the Number of Progenitor Cells upon Expansion.

We aimed to investigate whether a novel technique of human amniotic membrane (HAM) preparation that mimics the crypts in the limbus enhances the number of progenitor cells cultured ex vivo. The HAMs were sutured on polyester membrane (1) standardly, to obtain a flat HAM surface, or (2) loosely, achieving the radial folding to mimic crypts in the limbus. Immunohistochemistry was used to demonstrate a higher number of cells positive for progenitor markers p63α (37.56 ± 3.34% vs. 62.53 ± 3.32%, p = 0.01) and SOX9 (35.53 ± 0.96% vs. 43.23 ± 2.32%, p = 0.04), proliferation marker Ki-67 (8.43 ± 0.38 % vs. 22.38 ± 1.95 %, p = 0.002) in the crypt-like HAMs vs. flat HAMs, while no difference was found for the quiescence marker CEBPD (22.99 ± 2.96% vs. 30.49 ± 3.33 %, p = 0.17). Most of the cells stained negative for the corneal epithelial differentiation marker KRT3/12, and some were positive for N-cadherin in the crypt-like structures, but there was no difference in staining for E-cadherin and CX43 in crypt-like HAMs vs. flat HAMs. This novel HAM preparation method enhanced the number of progenitor cells expanded in the crypt-like HAM compared to cultures on the conventional flat HAM.

Intravitreal anti-vascular endothelial growth factor therapy for retinal diseases in Norway from 2011 to 2021: A combined registry and survey study.

PURPOSE: To investigate the use of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy in Norway from 2011 to 2021 and explore how the eye departments organized their injection services. METHODS: We combined data from the Norwegian Patient Registry (NPR) with survey responses from Norway's 22 eye departments. The NPR data encompassed all registered intravitreal injection episodes from 2011 to 2021. The survey contained questions about local treatment practices and emphasized neovascular age-related macular degeneration (nAMD), retinal vein occlusion and diabetic macular edema. RESULTS: A total of 47247 unique patients received 841 646 intravitreal injections in the study period. The number of patients per year increased from 6522 in 2011 to 20 635 in 2021. The number of injections per year increased from 30 926 in 2011 to 125 258 in 2021. The most frequent diagnosis was nAMD. In 2021, the age-adjusted treatment activity in Norway's 11 counties ranged from 47.8 to 75.5 injections per 1000 inhabitants aged ≥50 years. The use of aflibercept gradually exceeded bevacizumab, but the aflibercept proportion per county ranged from 38 to 82% in 2021. The survey revealed varying treatment practices, local guidelines were often absent, and only half of the departments defined a lower visual limit for initiating or maintaining treatment. CONCLUSION: The use of intravitreal anti-VEGF therapy increased considerably from 2011 to 2021, but there was considerable regional variation in treatment activity, drug utilization and organization of injection services. These findings emphasize the need for strengthened governance and national guidelines to ensure equal treatment nationally.

A Pilot Study of Implementing Diabetic Retinopathy Screening in the Oslo Region, Norway: Baseline Results.

PURPOSE: to gain insight into the baseline parameters of a population with diabetes mellitus (DM) included in a pilot diabetic retinopathy (DR) screening program at Oslo University Hospital (OUH), Norway. METHODS: This was a cross-sectional study of a cohort of adult patients (≥18 years) with type 1 or 2 DM (T1D and T2D). We measured the best-corrected visual acuity (BCVA), blood pressure (BP), heart rate (HR), intraocular pressure (IOP), height and weight. We also collected HbA1c, total serum cholesterol and urine-albumin, -creatinine and -albumin-to-creatinine ratio (ACR), as well as socio-demographic parameters, medications and previous screening history. We obtained color fundus photographs, which were graded by two experienced ophthalmologists according to the International Clinical Disease Severity Scale for DR. RESULTS: The study included 180 eyes of 90 patients: 12 patients (13.3%) had T1D and 78 (86.7%) had T2D. In the T1D group, 5 patients (41.7%) had no DR, and 7 (58.3%) had some degree of DR. In the T2D group, 60 patients (76.9%) had no DR, and 18 (23.1%) had some degree of DR. None of the patients had proliferative DR. Of the 43 patients not newly diagnosed (time of diagnosis > 5 years for T1D and >1 years for T2D), 37.5% of the T1D patients and 5.7% of the T2D patients had previously undergone regular screening. Univariate analyses found for the whole cohort significant associations between DR and age, HbA1c, urine albumin-to-creatinine ratio, body mass index (BMI) and duration of DM. For the T2D group alone, there were significant associations between DR and HbA1c, BMI, urine creatinine, urine albumin-to-creatinine ratio and duration of DM. The analysis also showed three times higher odds for DR in the T1D group than the T2D group. CONCLUSIONS: This study underscores the need for implementing a systematic DR screening program in the Oslo region, Norway, to better reach out to patients with DM and improve their screening adherence. Timely and proper treatment can prevent or mitigate vision loss and improve the prognosis. A considerable number of patients were referred from general practitioners for not being followed by an ophthalmologist.Among patients not newly diagnosed with DM, 62.8% had never had an eye exam, and the duration of DM for these patients was up to 18 years (median: 8 years).

Ex Vivo Pig Eye Model for Studying Diffusion of Acylcarnitines with Different Physicochemical Properties.

Purpose: To explore the diffusion capacities between the anterior and vitreous chambers in a novel ex vivo pig eye model using a mix of stable isotope-labeled acylcarnitines representing metabolites with different physical and chemical properties, and analysis using mass spectrometry (MS). Methods: Enucleated pig eyes were injected in the anterior or vitreous chamber of the eye with a stable isotope-labeled acylcarnitine mix (free carnitine, C2, C3, C4, C8, C12, and C16-having an increasing size and hydrophobicity in that order). Samples were collected from each chamber at 3, 6, and 24 h postincubation for analysis using MS. Results: After injection into the anterior chamber, the concentration of all acylcarnitines increased in the vitreous chamber over the observation period. After injection in the vitreous chamber, the acylcarnitines diffused to the anterior chamber with the highest concentration observed at 3 h postinjection, followed by a decrease in concentration possibly due to an elimination from the anterior chamber despite continued diffusion from the vitreous chamber. C16, the most hydrophobic and longest chain molecule, showed slower diffusion in both experimental settings. Conclusion: We hereby show a distinct diffusion pattern of molecules with different molecular size and hydrophobicity within and between the anterior and vitreous chamber. This model can be useful for optimizing choices and design of therapeutic molecules with higher retaining or depot properties into the two chambers of the eye for future intravitreal, intracameral, and topical treatment purposes.

Pharmaceutical compounding and storage of faricimab in a syringe for intravitreal injection do not impair stability and bi-specific binding properties.

BACKGROUND: Intravitreal injection (IVI) of antibody biologics is a key treatment approach in ophthalmology. Pharmaceutical compounding and storage of prefilled syringes for IVI must take place without impairing the structure and function of the biologics. This study investigated the effect of withdrawing and storing the therapeutic antibody faricimab (Vabysmo, Roche, Basel, Switzerland) in the Zero Residual silicone oil-free, 0.2-mL syringe (SJJ Solutions, The Hague, the Netherlands). METHODS: To assess the effect of syringe withdrawal on faricimab, we compared samples from syringes prepared at day 0 with samples taken directly from faricimab vials. To assess the effect of syringe storage on faricimab, we kept prefilled syringes in the dark at 4 oC for 7, 14, or 37 days and compared samples from these syringes with day 0. We measured protein concentration (with spectrophotometry), stability and integrity (with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), size-exclusion chromatography (SEC), and melting temperature (Tm)), as well as binding of faricimab to its cognate antigens: vascular endothelial growth factor A (VEGF-A) and angiopoietin-2 (Ang-2) (with enzyme-linked immunosorbent assay (ELISA)). RESULTS: Faricimab migrated in line with its expected molecular mass under both reducing and non-reducing conditions for all time points when analyzed with SDS-PAGE, without any sign of degradation products or aggregation. The SEC elution profiles were identical for all time points. There were slight variations in Tm for different time points compared to day 0 but without consistent relationship with storage time. ELISA did not detect differences in VEGF-A or Ang-2 binding between time points, and faricimab did not bind the neonatal Fc receptor. CONCLUSIONS: Withdrawal and storage of faricimab in syringes for up to day 37 did not impair the structure and bi-specific binding properties of the therapeutic antibody.

International Olympic Committee (IOC) consensus paper on sports-related ophthalmology issues in elite sports.

Vision plays an important role in an athletes' success. In sports, nearly 80% of perceptual input is visual, and eye health and sports medicine are closely intertwined fields of utmost importance to athletes. The physical nature of sports activities renders individuals more prone to various eye injuries than the general population. Ocular trauma can lead to lifelong sequelae, and impaired vision requires careful follow-up and management. Apart from injuries, athletes may also experience vision problems that can hamper their performance, including blurred vision, double vision, and light sensitivity. The interdisciplinary nature of sports medicine necessitates collaboration between sports medicine professionals and ophthalmologists. Through such collaborations, athletes can receive appropriate eye care, education on proper eye protection and guidance on adopting good eye health practices. If any inconspicuous symptoms are not detected and treated promptly, athletes may acquire systemic injuries because of defective vision, preventing them from achieving high level athletic performance in competitions. The protection of the elite athlete is the responsibility of all of us in sports medicine. To advance a more unified, evidence-informed approach to ophthalmic health assessment and management in athletes and as relevant for sports medicine physicians, the International Olympic Committee Consensus Group aims for a critical evaluation of the current state of the science and practice of ophthalmologic issues and illness in high-level sports, and present recommendations for a unified approach to this important issue.

A comparative study of the structural organization of spheres derived from the adult human subventricular zone and glioblastoma biopsies.

Sphere forming assays have been useful to enrich for stem like cells in a range of tumors. The robustness of this system contrasts the difficulties in defining a stem cell population based on cell surface markers. We have undertaken a study to describe the cellular and organizational composition of tumorspheres, directly comparing these to neurospheres derived from the adult human subventricular zone (SVZ). Primary cell cultures from brain tumors were found to contain variable fractions of cells positive for tumor stem cell markers (CD133 (2-93%)/SSEA1 (3-15%)/CXCR4 (1-72%)). All cultures produced tumors upon xenografting. Tumorspheres contained a heterogeneous population of cells, but were structurally organized with stem cell markers present at the core of spheres, with markers of more mature glial progenitors and astrocytes at more peripheral location. Ultrastructural studies showed that tumorspheres contained a higher fraction of electron dense cells in the core than the periphery (36% and 19%, respectively). Neurospheres also contained a heterogeneous cell population, but did not have an organization similar to tumorspheres. Although tumorspheres clearly display irregular and neoplastic cells, they establish an organized structure with an outward gradient of differentiation. We suggest that this organization is central in maintaining the tumor stem cell pool.

Does Pharmaceutical Compounding of Vascular Endothelial Growth Factor Inhibitors for Intravitreal Use Alter the Risk of Post-injection Endophthalmitis?

PURPOSE: To investigate the safety of pharmaceutically compounded syringes for intravitreal administration of anti-vascular endothelial growth factor (anti-VEGF) drugs. METHODS: Single center, retrospective chart review. From 2015 to 2019, Oslo University Hospital, Norway gradually implemented pharmaceutical compounding and splitting of bevacizumab, ranibizumab, and aflibercept vials into multiple prefilled syringes for intravitreal use. Medical records of all post-injection endophthalmitis (PIE) cases in this 5-year period were reviewed. The incidences of PIE associated with compounded and clinician-withdrawn syringes were compared. RESULTS: In 5 years, the total number of anti-VEGF injections was 112,926; 68,150 procedures (60%) utilized compounded syringes, and 44,776 procedures (40%) utilized clinician-withdrawn syringes. A total of 11 PIE cases were identified (incidence 0.10 per 1000; 95% CI 0.05-0.17). Five PIE cases were associated with compounded syringes (incidence 0.07 per 1000; 95% CI 0.03-0.17); 3 of these were culture positive. Six PIE cases were associated with clinician-withdrawn syringes (incidence 0.13 per 1000; 95% CI 0.06-0.29); 2 of these were culture positive. The relative risk of PIE following procedures utilizing compounded versus clinician-withdrawn syringes was 0.55 (95% CI 0.17-1.79; p = 0.32). CONCLUSION: Use of compounded anti-VEGF drugs in a large clinical setting was not associated with an altered risk of PIE. The finding adds to the evidence that splitting of vials into prefilled syringes for intravitreal injections is safe, provided that an appropriate pharmaceutical compounding procedure is strictly followed.

Healthcare expenditure of intravitreal anti-vascular endothelial growth factor inhibitors compared with dexamethasone implant for diabetic macular oedema.

PURPOSE: The aim of this study was to estimate the 1-year costs associated with treating diabetic macular oedema (DME) patients using current intravitreal anti-vascular endothelial growth factor (anti-VEGF) biologics compared with the dexamethasone implant. METHODS: We conducted a descriptive cost-evaluation analysis using data from Oslo University Hospital and literature to compare three different intravitreal drugs for DME: bevacizumab, aflibercept and dexamethasone. Stratification of patients into 'Naive' or 'Switch' group was based on treatment history. We estimated the costs from healthcare and 'extended' healthcare perspectives. Sensitivity analysis evaluated the impact of various parameters. RESULTS: The average injections per patient per year for the Naive group (bevacizumab), Switch group (aflibercept) and dexamethasone were 9.5, 9.1 and 3.0 respectively. From a healthcare perspective, the 1-year costs for the Naive group were 15% lower (bevacizumab, €3619), and for the Switch group, 23% higher (aflibercept, €5226) compared with dexamethasone (€4252). The 'extended' healthcare perspective showed the cost per patient per year for bevacizumab remained nominally lower in the Naive group, while dexamethasone remained lower for the Switch group (€5116 for dexamethasone, compared to €4987 for bevacizumab and €6537 for aflibercept). CONCLUSIONS: From a primary healthcare perspective, the dexamethasone as a first-line DME treatment may increase economic costs in settings where bevacizumab is used off-label. Treating resistant DMEwith dexamethasone may reduce the costs and treatment burden compared with switching to aflibercept.