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A dark‐field ophthalmic contact probe for analysis of aqueous humor (AH) was designed by ray tracing and constructed in quartz glass for experimental use as a prototype probe in a confocal Raman spectroscopic setup. The misalignment tolerance of this probe was theoretically evaluated, whereas the optical performance was experimentally evaluated by a concentration curve of the ocular drug phenylephrine HCl in an artificial eye model. The results indicated a ninefold improvement in misalignment tolerance and a 36‐fold improvement in the signal‐to‐noise ratio at the phenylephrine HCl 1002 cm−1 peak compared with a previous design. The prototype showed a good linear fit with the phenylephrine HCl concentration, with an R2 of 0.996. Phenylephrine HCl concentration down to 0.1% is detectable. [ABSTRACT FROM AUTHOR]

The purpose of this systematic review is to identify techniques used for quantification of choriocapillaris (CC) flow in eyes with uveitis using optical coherence tomography angiography (OCTA), report reliability and level of correlation with techniques such as indocyanine green angiography (ICGA). A systematic search of several databases was done. The studies were analyzed for techniques of measurement, reliability, and correlation with other modalities. Risk of bias assessment was performed. Thirteen studies were included. CC vessel density (7 studies) and flow deficit area (4 studies) were the most used indices. There was significant heterogeneity in the studies due to differences in the scan protocol, thresholding strategy, and analysis. Comparison with ICGA was performed by only one study, and reliability indices were reported by only two studies. OCTA is a useful tool to measure the CC vascularity in eyes with uveitis. However, standardized acquisition and analysis protocols are needed. [ABSTRACT FROM AUTHOR]

Purpose: Raman spectroscopy holds potential for the assessment of intraocular pharmacokinetics. Raman spectra of ocular drugs were acquired, to determine the drug-specific Raman signature. The ability of the Raman technique to quantify drug concentrations was also investigated. Methods: The experimental setup was based on a High Performance Raman Module 2500 Raman module, designed for 180° 'backscatter' signal detection in the wavenumber range of 400-1,800 cm−1. Excitation source was a diode laser emitting a beam with a wavelength of 785 nm and a power of 10 mW. Laser light was focused in the sample with a long-working-distance microscope objective (25×/0.50). Samples were measured in quartz cuvettes in 10 sequential measurements, with exposure time 30 s. The total number of measured drugs was 49. To determine whether signal intensity and drug concentration correlate, 2 drugs were diluted in water and measured with 120 s exposure time at different concentrations. Results: An active ingredient-specific Raman signature was detected in 4 glaucoma drugs, 6 mydriatics, 5 antibiotics, 4 anesthetics, 3 anti-inflammatory drugs, 2 types of artificial tears, and 5 other drugs. In 20 drugs, no specific Raman signature was detected. Linear correlation of drug concentration with signal intensity was high ( R2≥0.94). Conclusions: Using low laser powers, Raman signatures for 29 commonly used ocular drugs were detected. Correlation of drug concentration with signal intensity is high, which is essential for monitoring drug concentration in ocular media. The presented results encourage the use of Raman spectroscopy to acquire detailed information on the pharmacokinetics of these ocular drugs. [ABSTRACT FROM AUTHOR]

The aim is to analyze automated quantification of choriocapillaris flow deficit (CCFD) on swept-source (SS)-optical coherence tomography angiography (OCTA) in tubercular serpiginous-like choroiditis (TBSLC). In this prospective study, automated CCFD calculations were performed on SS-OCTA and compared with CCFD areas on indocyanine green angiography (ICGA). Patients were divided into two groups based on the occurrence of paradoxical worsening (PW). Twenty-nine eyes (29 subjects; 18 males; mean age: 33±12 years) were included. The mean CCFD at baseline was 34.9 ± 4.3% on OCTA in eyes without PW and 35.4 ± 5.0% on SS-OCTA with PW (p =.77). At 4 and 12 weeks, CCFD on SS-OCTA improved to 30.6 ± 3.9% and 28.0 ± 4.2% (p <.001) without PW, respectively, and increased to 42.9 ± 4.4% and 48.8 ± 4.1% (p <.001) with PW, respectively. The SS-OCTA CCFD correlated well with ICGA (r = 0.48; p <.001). Automated quantitative serial assessment of CCFD on SS-OCTA can serve as a useful biomarker of disease activity in eyes with TBSLC. [ABSTRACT FROM AUTHOR]

To obtain a real-time noninvasive analysis of the content of the aqueous humor (AH) in the eye, a confocal dark-field ophthalmic probe was designed and optimized by ray-tracing software. The confocal technique allows Raman spectrometric sampling of the AH with suppressing signals from the surrounding tissues. Dark-field illumination prevents the excitation light to reach the vulnerable retinal tissue directly. In order to evaluate the optical performance and safety of this method, a functional prototyped eye contact probe has been designed and tested on ex vivo rabbit eyes. [ABSTRACT FROM AUTHOR]

In this report we present a confocal Raman system to identify the unique spectral features of two proteins, Interleukin-10 and Angiotensin Converting Enzyme. Characteristic Raman spectra were successfully acquired and identified for the first time to our knowledge, showing the potential of Raman spectroscopy as a non-invasive investigation tool for biomedical applications. [ABSTRACT FROM AUTHOR]

To quantify retinochoroidal vascular parameters using swept-source optical coherence tomography (SS-OCTA) in quiescent posterior and panuveitis. In this cross-sectional study, subjects with quiescent posterior and panuveitis underwent fundus imaging using SS-OCTA (DRI Triton®, Topcon, Japan). The metrics calculated were fractal dimension (FD), foveal avascular zone (FAZ) area, retinal vascularity index (capillary density index-CDI), and choroidal vascularity index (CVI). We included 38 eyes of 20 patients, 9 males aged 34.7 ± 10.5 years, 30 eyes of 30 age- and gender-matched healthy controls, 10 females aged 33.6 ± 8.5 years. Comparing patients with controls, we found a lower FD (p <.001), larger FAZ (p >.001), lower CDI in the superficial plexus (p =.019), and lower CVI (p <.001). We also found lower retinal and choroidal and thicknesses (p <.001 and p =.025, respectively). Patients with quiescent posterior and panuveitis have a significantly reduced retinochoroidal vascular density compared to healthy control subjects. [ABSTRACT FROM AUTHOR]

Scleritis is a severe and painful ophthalmic disorder, in which a pathogenic role for collagen-directed autoimmunity was repeatedly suggested. We evaluated the presence of sclera-specific antibodies in a large cohort of patients with non-infectious scleritis. Therefore, we prospectively collected serum samples from 121 patients with non-infectious scleritis in a multicenter cohort study in the Netherlands. In addition, healthy (n = 39) and uveitis controls (n = 48) were included. Serum samples were tested for anti-native human type II collagen antibodies using a validated enzyme-linked immunosorbent assay (ELISA). Further, sclera-specific antibodies were determined using indirect immunofluorescence (IIF) on primate retinal/scleral cryosections. Lastly, human leukocyte antigen (HLA) typing was performed in 111 patients with scleritis. Anti-type II collagen antibodies were found in 13% of scleritis patients, in 10% of healthy controls and in 11% of uveitis controls (p = 0.91). A specific reaction to scleral nerve tissue on IIF was observed in 33% of patients with scleritis, which was higher than in healthy controls (11%; p = 0.01), but similar to uveitis controls (25%; p = 0.36). Reactivity to the scleral nerve tissue was significantly associated with earlier onset of scleritis (48 versus 56 years; p < 0.001), bilateral involvement (65% versus 42%; p = 0.01), and less frequent development of scleral necrosis (5% versus 22%; p = 0.02). HLA-B27 was found to be twice as prevalent in patients with scleritis (15.3%) compared to a healthy population (7.2%). In conclusion, scleral nerve autoantibody reactivity was more common in scleritis and uveitis patients in contrast to healthy controls. Further research is needed to characterize these scleral-nerve directed antibodies and assess their clinical value. [Display omitted] • Scleral nerve autoantibody reactivity is more common in patients with scleritis and uveitis compared to healthy controls. • Type II collagen antibodies were not found to occur more frequently in patients with scleritis compared to healthy controls. • A significant association with HLA-B27 is present in patients with scleritis compared to healthy controls. [ABSTRACT FROM AUTHOR]

Purpose: To compare differences in choriocapillaris flow deficit (CC FD) in multifocal choroiditis (MFC) between two treatment arms using optical coherence tomography angiography (OCTA). Methods: In this prospective randomized clinical trial, patients were randomized to either Group 1 which received standard tapering dose of oral corticosteroids, or Group 2 which received additional dexamethasone implant (or intravitreal methotrexate). The patients were followed-up until 12 weeks using OCTA and other imaging tools. CC FD and visual acuity between the two groups were compared at each visit. Results: Twenty-five subjects (17 males; 25 eyes) were studied (11 eyes in Group 1). There were no differences between the visual acuity or CC FD (1.12 versus 1.08 mm2; p = 0.86) at baseline between the groups. However, patients in Group 2 achieved better visual acuity (0.32 ± 0.23 versus 0.15 ± 0.11; p = 0.025) and CC FD (0.54 versus 0.15 mm2; p = 0.008) at 12 weeks. Conclusions: OCTA is a useful tool in monitoring the CC FD recovery after treatment in MFC. Patients receiving intravitreal corticosteroid/methotrexate in addition to systemic corticosteroid showed greater resolution of CC FD on OCTA compared to those receiving only oral corticosteroids. [ABSTRACT FROM AUTHOR]

Current information about the pharmacokinetics of an ocular drug can only be achieved by invasive sampling. However, confocal Raman spectroscopy bears the potential to quantify drug concentrations non-invasively. In this project, we evaluated the detection and quantification of ocular ketorolac tromethamine levels with confocal Raman spectroscopy after topical administration. Confocal Raman spectroscopy and high-performance liquid chromatography (HPLC) were compared in terms of sensitivity of detection. Enucleated pig eyes were treated with different concentrations of ketorolac. Hereafter, ketorolac concentrations in the aqueous humor of pig eyes were analyzed by confocal Raman spectroscopy and HPLC. Subsequently, twelve rabbits were treated with Acular™ for four weeks. At several time points, ketorolac concentrations in aqueous humor of the rabbits were measured by confocal Raman spectroscopy followed by drawing an aqueous humor sample for HPLC analysis. In ketorolac treated pig eyes, both ex vivo Raman spectroscopy as well as HPLC were able to detect ketorolac in a broad concentration range. However, in vivo confocal Raman spectroscopy in rabbits was unable to detect ketorolac in contrast to HPLC. To conclude, confocal Raman spectroscopy has the capacity to detect ketorolac tromethamine in vitro , but currently lacks sensitivity for in vivo detection. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To evaluate long‐term outcomes on efficacy and safety of severe uveitic glaucoma treated with a Baerveldt glaucoma implant (BGI). Methods: A retrospective study of 47 eyes of 47 patients with uveitic glaucoma treated by a BGI between September 2002 and September 2015. Main outcome measures were intraocular pressure (IOP), number of glaucoma medications, course of the uveitis, visual acuity (VA) and complications. Results: Mean IOP dropped from 30.6 ± 8.1 mmHg with 3.6 ± 1.1 glaucoma medications at baseline to 10.6 ± 4.3 mmHg with 1.0 ± 1.3 glaucoma medications after a mean follow‐up of 63.6 ± 43.1 months. In the majority of cases, IOP remained stable during follow‐up. However, especially in several patients with viral uveitis, episodes with IOP peaks were observed during a flare‐up despite a functioning implant. These peaks remained below preoperative levels. During follow‐up, 16 patients (34%) experienced a clinically significant VA loss, mainly because of late‐stage glaucoma or hypotony maculopathy. Early postoperative complications were transient choroidal effusion (n = 5), shallow/flat anterior chamber (n = 4), hyphaema (n = 2) and suprachoroidal haemorrhage (n = 1). The most important late postoperative complication was hypotony maculopathy (n = 5), three of these in juvenile idiopathic arthritis (JIA) patients. Conclusion: The BGI is an effective and safe treatment for patients with refractive secondary glaucoma due to uveitis. In a majority of patients, VA remains stable and a low and stable IOP is maintained over time with an acceptable number of complications. In particular, patients with viral uveitis and glaucoma should be closely monitored for IOP peaks that may occur during episodes of a flare‐up of uveitis, whereas at the other end of the spectrum, patients with JIA seem much more prone to hypotony maculopathy. [ABSTRACT FROM AUTHOR]