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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.

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.

Purpose: To quantify retinochoroidal vascular parameters using swept-source optical coherence tomography (SS-OCTA) in quiescent posterior and panuveitis. Methods: 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). Results: 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). Conclusions: Patients with quiescent posterior and panuveitis have a significantly reduced retinochoroidal vascular density compared to healthy control subjects.

Purpose To quantify retinochoroidal vascular parameters using swept-source optical coherence tomography (SS-OCTA) in quiescent posterior and panuveitis. Methods In this cross-sectional study, subjects with quiescent posterior and panuveitis underwent fundus imaging using SS-OCTA (DRI Triton (R), 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). Results 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 p = .025, respectively). Conclusions Patients with quiescent posterior and panuveitis have a significantly reduced retinochoroidal vascular density compared to healthy control subjects.

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.

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.

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 (TM) 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.

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.

This article includes datasets acquired by Raman spectroscopy from in vivo and in vitro ocular samples collected from the dataset from Bertens and Zhang et al., “Confocal Raman spectroscopy: Evaluation of a non-invasive technique for the detection of topically applied ketorolac tromethamine in vitro and in vivo” (Bertens and Zhang, et al.). Detection of ketorolac tromethamine in pig eyes was performed in vitro and rabbit eyes in vivo. Extracted aqueous humor samples from pig and rabbit eyes were measured in vitro using a cuvette. This manuscript shows the spectral Raman data without pre-treatment or analysis from ocular tissues and provides further information towards aqueous humor research via alternative data processing methods. Furthermore, the raw data enclosed may be used for future aqueous humor investigations and pharmaceutical research.

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.