Using Deep Learning to Distinguish Highly Malignant Uveal Melanoma from Benign Choroidal Nevi.

Background: This study aimed to evaluate the potential of human-machine interaction (HMI) in a deep learning software for discerning the malignancy of choroidal melanocytic lesions based on fundus photographs. Methods: The study enrolled individuals diagnosed with a choroidal melanocytic lesion at a tertiary clinic between 2011 and 2023, resulting in a cohort of 762 eligible cases. A deep learning-based assistant integrated into the software underwent training using a dataset comprising 762 color fundus photographs (CFPs) of choroidal lesions captured by various fundus cameras. The dataset was categorized into benign nevi, untreated choroidal melanomas, and irradiated choroidal melanomas. The reference standard for evaluation was established by retinal specialists using multimodal imaging. Trinary and binary models were trained, and their classification performance was evaluated on a test set consisting of 100 independent images. The discriminative performance of deep learning models was evaluated based on accuracy, recall, and specificity. Results: The final accuracy rates on the independent test set for multi-class and binary (benign vs. malignant) classification were 84.8% and 90.9%, respectively. Recall and specificity ranged from 0.85 to 0.90 and 0.91 to 0.92, respectively. The mean area under the curve (AUC) values were 0.96 and 0.99, respectively. Optimal discriminative performance was observed in binary classification with the incorporation of a single imaging modality, achieving an accuracy of 95.8%. Conclusions: The deep learning models demonstrated commendable performance in distinguishing the malignancy of choroidal lesions. The software exhibits promise for resource-efficient and cost-effective pre-stratification.

AI-driven discovery of blood xenobiotic biomarkers in neovascular age-related macular degeneration using iterative random forests.

PURPOSE: To investigate the xenobiotic profiles of patients with neovascular age-related macular degeneration (nAMD) undergoing anti-vascular endothelial growth factor (anti-VEGF) intravitreal therapy (IVT) to identify biomarkers indicative of clinical phenotypes through advanced AI methodologies. METHODS: In this cross-sectional observational study, we analyzed 156 peripheral blood xenobiotic features in a cohort of 46 nAMD patients stratified by choroidal neovascularization (CNV) control under anti-VEGF IVT. We employed Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) for measurement and leveraged an AI-driven iterative Random Forests (iRF) approach for robust pattern recognition and feature selection, aligning molecular profiles with clinical phenotypes. RESULTS: AI-augmented iRF models effectively refined the metabolite spectrum by discarding non-predictive elements. Perfluorooctanesulfonate (PFOS) and Ethyl ß-glucopyranoside were identified as significant biomarkers through this process, associated with various clinically relevant phenotypes. Unlike single metabolite classes, drug metabolites were distinctly correlated with subretinal fluid presence. CONCLUSIONS: This study underscores the enhanced capability of AI, particularly iRF, in dissecting complex metabolomic data to elucidate the xenobiotic landscape of nAMD and environmental impact on the disease. The preliminary biomarkers discovered offer promising directions for personalized treatment strategies, although further validation in broader cohorts is essential for clinical application.

[Vasculitis of the retina : Clinical aspects, diagnostics, management and treatment]. / Vaskulitis der Retina : Klinik, Diagnostik, Management und Therapie.

Inflammatory changes in the retinal vessels can be attributed to a wide range of etiologies. These include infections, intraocular and systemic autoimmune processes, general diseases and iatrogenic factors. As the endothelium of the retinal capillaries forms the inner blood-retinal barrier, a disruption of this structure is directly associated with consequences for the fluid electrolyte balance of the retina. Clinical sequelae can include leakage of the retinal vessels and macular edema, which are often functionally threatening and significantly reduce the quality of life of patients. As the eye can be affected as an "index organ", a work-up of the patient by the ophthalmologist is of great importance. In the age of "precision medicine", efforts are being made to gain new insights into the pathogenetic mechanisms of vasculitis through "omics" in order to develop innovative treatment concepts.

Fluocinolone Acetonide Implant for Uveitis: Dissecting Responder and Non-Responder Outcomes at a Tertiary Center.

Macular edema (ME) remains a primary cause of visual deterioration in uveitis. Visual acuity (VA) can often be maintained using corticosteroid depot systems. This study evaluated the efficacy of a fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN®) in treating non-infectious uveitis using real-world data. This retrospective analysis included 135 eyes subdivided into responders and non-responders. Central retinal thickness (CRT), VA, and intraocular pressure (IOP) were followed over time. A significant decrease in CRT and an increase in VA were observed in all eyes throughout the follow-up period (p < 0.01). An IOP increase (p = 0.028) necessitated treatment in 43% of eyes by Month 6. Non-responders were older (p = 0.004) and had been treated with more dexamethasone (DEX) implants (p = 0.04); 89.3% had a defect in the external limiting membrane (ELM) and inner/outer segment (IS/OS) zone (p < 0.001). Immunomodulatory therapy had no impact on treatment response. Pars plana vitrectomy (PPV) patients had a mean CRT reduction of 47.55 µm and a reduced effect by Month 24 (p = 0.046) versus non-PPV patients. We conclude that the FAc implant achieves long-term control of CRT and improves VA. Increases in IOP were manageable. Eyes with a previous PPV showed milder results. Data showed a correlation between older age, a damaged ELM and IS/OS zone, frequent DEX inserts, and poorer outcome measures.

Exploring the Impact of Saccharin on Neovascular Age-Related Macular Degeneration: A Comprehensive Study in Patients and Mice.

Purpose: We aimed to determine the impact of artificial sweeteners (AS), especially saccharin, on the progression and treatment efficacy of patients with neovascular age-related macular degeneration (nAMD) under anti-vascular endothelial growth factor (anti-VEGF-A) treatment. Methods: In a cross-sectional study involving 46 patients with nAMD undergoing intravitreal anti-VEGF therapy, 6 AS metabolites were detected in peripheral blood using liquid chromatography - tandem mass spectrometry (LC-MS/MS). Disease features were statistically tested against these metabolite levels. Additionally, a murine choroidal neovascularization (CNV) model, induced by laser, was used to evaluate the effects of orally administered saccharin, assessing both imaging outcomes and gene expression patterns. Polymerase chain reaction (PCR) methods were used to evaluate functional expression of sweet taste receptors in a retinal pigment epithelium (RPE) cell line. Results: Saccharin levels in blood were significantly higher in patients with well-controlled CNV activity (P = 0.004) and those without subretinal hyper-reflective material (P = 0.015). In the murine model, saccharin-treated mice exhibited fewer leaking laser scars, lesser occurrence of bleeding, smaller fibrotic areas (P < 0.05), and a 40% decrease in mononuclear phagocyte accumulation (P = 0.06). Gene analysis indicated downregulation of inflammatory and VEGFR-1 response genes in the treated animals. Human RPE cells expressed taste receptor type 1 member 3 (TAS1R3) mRNA and reacted to saccharin stimulation with changes in mRNA expression. Conclusions: Saccharin appears to play a protective role in patients with nAMD undergoing intravitreal anti-VEGF treatment, aiding in better pathological lesion control and scar reduction. The murine study supports this observation, proposing saccharin's potential in mitigating pathological VEGFR-1-induced immune responses potentially via the RPE sensing saccharin in the blood stream.

Viral Anterior Uveitis: Differences in Retinal Vessel Area Density between the Affected and Non-Affected Eye Using Optical Coherence Tomography Angiography.

PURPOSE: To investigate differences in the retinal vessel area density (VAD) on optical coherence tomography angiography (OCTA) between eyes with unilateral herpetic viral anterior uveitis (VAU) (herpes-simplex virus (HSV) and varicella-zoster virus (VZV)) and the non-affected fellow eye. METHODS: In this monocentric, observational, prospective case series we analyzed the VAD of the macula, optic disc, and peripapillary region in affected and non-affected eyes of 22 patients with HSV-positive and 22 patients with VZV-positive VAU using OCTA. We analyzed also the visual field mean deviation (MD), the retinal nerve fiber layer (RNFL) thickness, Bruch's Membrane Opening-Minimum Rim Width (BMO-MRW), and ganglion cell layer (GCL) thickness on OCT and correlated the results with the different VADs. RESULTS: The macular VAD in the superficial vascular plexus (SVC) was significant lower in the affected compared to the non-affected eye for both viruses (HSV: 33.0% ± 3.3% vs. 34.7% ± 2.6%, p = 0.011; adjusted p = 0.040; VZV: 33.1% ± 3.2% vs. 34.3% ± 2.8%, p = 0.012; adjusted p = 0.050). Additionally, the VAD of the peripapillary SVC differed between the affected and non-affected eye for VZV-positive VAU (47.1% ± 6.2% vs. 50.5% ± 6.3%, p = 0.048, adjusted p = 0.100). For both HSV-positive and VZV-positive VAU, there were correlations between macular or peripapillary SVC VAD and BMO-MRW, GCL thickness, RNFL thickness or MD of the affected eye. CONCLUSION: We observed vascular dysfunction characterized by decreased macular and peripapillary VAD in the superficial plexus on OCTA in eyes with HSV- and VZV-positive VAU compared to non-affected fellow eyes. These changes might be an early sign of glaucomatous damage or may be a direct consequence of the herpes viruses themselves.

Real-World Experience with Brolucizumab Compared to Aflibercept in Treatment-Naïve and Therapy-Refractory Patients with Diabetic Macular Edema.

Background: To report on the outcome of intravitreal brolucizumab compared to aflibercept in patients with diabetic macular edema (DME). Methods: Prospective, observational, study in 35 eyes of 24 patients with a loading dose of five injections of 6 mg brolucizumab every 6 weeks (q6w, treatment-naïve eyes) or a minimum of two injections of brolucizumab q6w after the switch (recalcitrant DME eyes), followed by a treat and extend (T&E) regimen. The results were compared with 40 eyes of 31 DME patients who were treated with aflibercept. The data were obtained from the Berlin Macula Registry. The primary outcome measure was the change in best-corrected visual acuity (BCVA) at week 36. Secondary outcome measures were the change in central retinal thickness (CRT) and the treatment intervals until week 36. Results: BCVA increased significantly in treatment-naïve DME eyes treated with either brolucizumab (+0.12 logMAR, +6.4 letters, p = 0.03) or aflibercept (+0.19 logMAR, +9.5 letters, p = 0.001). In recalcitrant DME eyes, BCVA also increased significantly after switching to brolucizumab (+0.1 logMAR, +5 letters, p = 0.006) or aflibercept (+0.11 logMAR, +5.5 letters, p = 0.02). All treatment-naïve and recalcitrant DME eyes had a significant decrease in CRT after treatment with brolucizumab (p = 0.001 and p < 0.001) or aflibercept (p = 0.0002 and p = 0.03). At week 36, the mean treatment interval for brolucizumab was 11.3 weeks, while for aflibercept, it was 6.5 weeks for treatment-naïve eyes and 9.3 weeks vs. 5.3 weeks for pretreated eyes. Conclusions: In routine clinical practice, patients with treatment-naïve and recalcitrant DME showed a favorable response to brolucizumab and aflibercept therapy, with a reduced injection frequency after brolucizumab treatment.

Cytomegalovirus-positive Posner-Schlossman syndrome: to compare differences in retinal vessel area density between the affected and non-affected eye using optical coherence tomography angiography.

PURPOSE: To analyse differences in the retinal microvasculature in eyes with cytomegalovirus (CMV)-positive Posner-Schlossman syndrome (PSS) compared to the non-affected eyes using optical coherence tomography angiography (OCTA). METHODS: In this monocentric, observational prospective case series, 25 patients with unilateral CMV-positive PSS were included. We compared the vessel area densities (VAD) in the macula, optic disc, and peripapillary region in PSS-affected and non-affected eyes using OCTA. We compared the visual fields (VF) of the affected and healthy eyes of each patient. The mean deviation (MD) of the VF was analysed together with the retinal nerve fibre layer (RNFL) thickness to evaluate the strength of correlation with the VAD parameters. RESULTS: The VAD of the peripapillary superficial vascular complex (SVC) is significantly reduced in CMV-positive PSS-affected eyes (46.1 ± 9.3% versus 50.1 ± 6.3%, p = 0.008, adjusted p = 0.048). The VAD of the deeper macular, papillary, and peripapillary layers showed no differences between the affected and non-affected eyes. The mean deviation and the retinal nerve fibre layer thickness had correlations with the VAD of the macula (r = 0.451, p = 0.001, r = 0.553, p < 0.001), the peripapillary SCV (r = 0.430, p = 0.002, r = 0.723, p < 0.001), and the papillary region (r = 0.512, p < 0.001, r = 0.292, p = 0.039). Patients receiving systemic antiviral therapy (SAT) showed better VAD of the peripapillary choriocapillary layer (p = 0.001, no therapy: 31.4 ± 1.9%, SAT: 35.0 ± 1.6%), and choroidal layer (p = 0.009, no therapy: 34.2 ± 0.3%, SAT: 36.3 ± 1.8%) compared to those with no SAT. CONCLUSION: A lower peripapillary VAD in the SVC might indicate vascular dysfunction as a sign of glaucomatous damage. SAT might have positive effects on the microcirculation in the deep retinal and choroidal layers. TRIAL REGISTRATION: TRN: DRKS00028266, https://www.drks.de/drks_web/ .

Systemic Blood Proteome Patterns Reflect Disease Phenotypes in Neovascular Age-Related Macular Degeneration.

There is early evidence of extraocular systemic signals effecting function and morphology in neovascular age-related macular degeneration (nAMD). The prospective, cross-sectional BIOMAC study is an explorative investigation of peripheral blood proteome profiles and matched clinical features to uncover systemic determinacy in nAMD under anti-vascular endothelial growth factor intravitreal therapy (anti-VEGF IVT). It includes 46 nAMD patients stratified by the level of disease control under ongoing anti-VEGF treatment. Proteomic profiles in peripheral blood samples of every patient were detected with LC-MS/MS mass spectrometry. The patients underwent extensive clinical examination with a focus on macular function and morphology. In silico analysis includes unbiased dimensionality reduction and clustering, a subsequent annotation of clinical features, and non-linear models for recognition of underlying patterns. The model assessment was performed using leave-one-out cross validation. The findings provide an exploratory demonstration of the link between systemic proteomic signals and macular disease pattern using and validating non-linear classification models. Three main results were obtained: (1) Proteome-based clustering identifies two distinct patient subclusters with the smaller one (n = 10) exhibiting a strong signature for oxidative stress response. Matching the relevant meta-features on the individual patient's level identifies pulmonary dysfunction as an underlying health condition in these patients. (2) We identify biomarkers for nAMD disease features with Aldolase C as a putative factor associated with superior disease control under ongoing anti-VEGF treatment. (3) Apart from this, isolated protein markers are only weakly correlated with nAMD disease expression. In contrast, applying a non-linear classification model identifies complex molecular patterns hidden in a high number of proteomic dimensions determining macular disease expression. In conclusion, so far unconsidered systemic signals in the peripheral blood proteome contribute to the clinically observed phenotype of nAMD, which should be examined in future translational research on AMD.

[Noninfectious posterior uveitis : Clinical aspects, diagnostics, management and treatment]. / Nichtinfektiöse posteriore Uveitis : Klinik, Diagnostik, Management und Therapie.

Noninfectious posterior uveitis (NPU) comprises a heterogeneous group of vision-threatening, immune-mediated ocular and systemic diseases. It is predominantly bilateral and recurrent and, if not treated properly, leads to severe tissue damage that threatens the eyesight. In industrialized countries ca. 10-20% of all cases of blindness are caused by NPU. An NPU can occur at any age but is most common between the ages of 20 and 50 years. Laboratory diagnostic and imaging procedures enable an increasingly better differentiation of the disease spectrum. This makes it possible to better assess the course and prognosis of individual disease entities. An increasing repertoire of systemic and intravitreal forms of treatment has already led to more favorable long-term treatment outcomes. It can be expected that further progress can be achieved with better knowledge of the pathophysiology of the different clinical disorders and appropriate, targeted treatment.

Treatment of neovascular age-related macular degeneration: insights into drug-switch real-world from the Berlin Macular Registry.

PURPOSE: Bevacizumab, ranibizumab, and aflibercept are commonly used to treat neovascular age-related macular degeneration (nAMD). The results of various interventional, mostly randomized head-to-head studies, indicate statistical non-inferiority of these three drugs. The results of these studies are often interpreted as the three drugs being freely interchangeable, resulting in some health systems to pressure ophthalmologists to preferentially use the less expensive bevacizumab. This study analyzes switching from aflibercept or ranibizumab to bevacizumab and back under real-world conditions in order to investigate the assumption of interchangeability of the drugs. METHODS: Treatment data of IVT patients with diagnosed nAMD were extracted from the clinical Berlin Macular Registry database. Patients who underwent a drug switch from aflibercept or ranibizumab to bevacizumab were subject of this study. Statistical comparisons were pre-planned for best corrected visual acuity, central retinal thickness, macular volume, and length of injection interval. Additional endpoints were analyzed descriptively. RESULTS: Mean visual acuity decreased from 0.57 ± 0.05 under aflibercept/ranibizumab to 0.68 ± 0.06 logMAR after the switch (P = 0.001; N = 63). CRT increased from 308 ± 11 µm to 336 ± 16 µm (P = 0.011; N = 63). About half of the subjects were switched back: visual acuity increased from 0.69 ± 0.08 logMAR to 0.58 ± 0.09 logMAR (N = 26). CRT decreased from 396 ± 28 to 337 ± 20 µm (N = 28). CONCLUSION: The data provides real-world evidence that there is loss of visual acuity and an increase in retinal edema after switching to bevacizumab. Thus, the assumption of free interchangeability cannot be confirmed in this cohort.

Anti-CD20 therapy for multiple sclerosis-associated uveitis: A case series.

BACKGROUND AND PURPOSE: Approximately 1% of patients with multiple sclerosis (MS) have uveitis, but data on the effects of immunotherapies for MS on MS-associated uveitis are scarce. The aim of this study was to investigate the ophthalmological outcomes in patients with MS-associated uveitis treated with anti-CD20 therapy. METHODS: A retrospective study of 12 eyes of six patients with MS-associated uveitis, refractory to previous immunotherapies, was conducted. Uveitis activity was assessed before initiation of anti-CD20 therapy and at regular follow-up visits. Primary outcome measures were: vitreous haze score; retinal vasculitis score, determined on fluorescein angiography images; macular edema, as quantified by central retinal thickness (CRT) on optical coherence tomography; and visual acuity (VA). Secondary outcomes included number of annualized uveitis or MS relapses, disease activity on cerebral magnetic resonance imaging (cMRI) and Expanded Disability Status Scale (EDSS) score. RESULTS: After a median (interquartile range [IQR]) treatment time of 28.5 (8-43) months, anti-CD20 therapy was associated with an improvement of vitreous haze score (p = 0.002), retinal vasculitis score (p = 0.001), CRT (p = 0.002), and VA (p = 0.007). The median (IQR) annualized uveitis relapse rate declined from 0.59 (0.56-0.94) before to 0 (0-0.49) after the start of anti-CD20 therapy. The median (IQR) annualized MS relapse rate declined from 0.62 (0.26-2.84) before to 0 (0-0) after the start of anti-CD20 therapy. After initiation of anti-CD20 therapy, there was no disease activity on cMRI, and EDSS score improved (n = 2) or remained stable (n = 4). No severe adverse events were observed. CONCLUSION: These findings suggest that anti-CD20 therapy may be a valuable treatment option for MS-associated uveitis.

A Comprehensive Update on Retinal Vasculitis: Etiologies, Manifestations and Treatments.

Retinal vasculitis is characterized by inflammatory involvement of retinal arterioles, venules and/or capillaries and can be associated with a myriad of systemic and ophthalmic diseases. In this review, we have comprehensively discussed the etiologies, clinical manifestations, and presentations of retinal vasculitis. We have also included newer advances in imaging in retinal vasculitis such as OCTA and widefield imaging.

Early OCT Angiography Changes of Macular Neovascularization in Patients with Exudative AMD Treated with Brolucizumab in a Real-World Setting.

Background: To report on the short-term outcome of intravitreal brolucizumab in patients with neovascular age-related macular degeneration (nAMD). Methods: This is a prospective, interventional, monocentric study on 10 eyes of 10 patients with a treatment-naïve neovascular AMD. Patients were treated according to the HAWK and HARRIER trials. After loading with 3 monthly injections, eyes received an injection 12 weeks after the upload (q12w) or were adjusted to an 8 week interval (q8w), if disease activity was present 8 weeks after the upload. Main outcome measures were the change in central retinal thickness (CRT) assessed by spectral domain optical coherence tomography (SD-OCT), the change in macular neovascularization (MNV) size on optical coherence tomography angiography (OCTA), and the change in best corrected visual acuity (BCVA) 8 and 12 weeks after the upload. We further assessed clinical parameters that predict the treatment response at baseline based on the need of q8w or q12w injections after the upload. Results: CRT decreased significantly from 461.7 ± 82.9 µm to 343.6 ± 74.3 µm (p=0.004) 12 weeks after the upload. The MNV size decreased significantly from 0.85 ± 1.1 to 0.75 ± 1.2 mm2 (p=0.022). BCVA improved from 0.67 ± 0.4 to 0.55 ± 0.4logMAR but without statistical significance. MNV size in eyes on q12w was considerably smaller compared to that in eyes on q8w (0.54 ± 0.7 mm2 vs. 1.98 ± 2.4 mm2). The percentage of eyes without any persistent fluid was 70% (7/10 eyes). Conclusions: Brolucizumab appears to be a valuable tool for the management of patients with nAMD. Furthermore, MNV size at baseline might serve as an early predictor of treatment response.

Macular, papillary and peripapillary perfusion densities measured with optical coherence tomography angiography in primary open angle glaucoma and pseudoexfoliation glaucoma.

PURPOSE: To compare the blood flow situation in primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG) using optical coherence tomography angiography (OCTA). METHODS: In this prospective study a total of 26 POAG and 23 PXG eyes were included. All patients underwent a complete ophthalmological examination including standard automated perimetry, stereoscopic photographs of the optic disc, peripapillary retinal nerve fibre layer analysis and examination of vascular parameters of the optic nerve head (ONH), the peripapillary region and macula using OCTA. In addition to the vascular parameters recorded by the device, the vascular images were graphically evaluated using Image J. All recorded vascular parameters were compared between both groups and correlated to structural and functional parameters. RESULTS: The mean superficial perifoveal plexus perfusion density (PD) was significantly lower in PXG eyes than compared to POAG eyes using OCTA (32.57% ± 3.57% vs. 34.92% ± 2.11%, p = 0.007). The mean PD parameters for the superficial peripapillary plexus (40.98% ± 3.04% vs. 42.09% ± 2.29%, p = 0.152) as well as the size of the foveal avascular zone (FAZ) (0.23 mm2 ± 0.1 mm2 vs. 0.23 mm2 ± 0.09 mm2) did not differ between both groups. Additional graphic evaluation using Image J showed no significant difference for superficial perifoveal plexus PD (32.97% ± 1.11% vs. 33.35% ± 0.95%, p = 0.194) and peripapillary plexus PD (46.65% ± 0.83% vs. 46.95% ± 0.5%, p = 0.127) between the groups. Retinal nerve fibre layer (RNFL) thickness correlated significantly with peripapillary plexus PD for both OCTA data and Image J data (p < 0.001, p = 0.032). CONCLUSION: The severity of the glaucoma seems to be crucial for peripapillary and macular perfusion densities, and not the form of glaucoma. An additional graphic evaluation is a possible step that could be implemented to improve the comparability of OCTA scans and to optimize the possibility of quantitative perfusion analysis in the case of deviating quality criteria.

Rubella Virus- and Cytomegalovirus-Associated Anterior Uveitis: Clinical Findings and How They Relate to the Current Fuchs Uveitis Syndrome Classification.

Rubella virus (RV) and cytomegalovirus (CMV) have both been implicated in anterior uveitis (AU). Clinical phenotypes can vary widely among both etiologies, including Fuchs uveitis syndrome (FUS) as a very distinct phenotype that has been associated with both RV and CMV. The Standardization of Uveitis Nomenclature (SUN) Working Group recently updated the classification criteria for FUS as unilateral AU, including either heterochromia or diffuse iris atrophy combined with stellate keratic precipitates as key findings. The aim of this study was to determine whether our patients adhere to the classification criteria of FUS as previously reported and whether RV- or CMV-associated uveitis can be differentiated by clinical findings. Therefore, this study investigated the clinical characteristics of patients with AU and intraocular presence of either RV or CMV determined by the Goldmann-Witmer coefficient (GWC). Our study included 100 patients (107 eyes) with AU and positive GWC for RV (86) and CMV (21). Clinical findings of RV-positive eyes were as follows: keratic precipitates (91.9%) with a predominantly diffuse distribution (81.4%), unilateral cataract (80.2%), pseudophakia (73.5%), and vitreous cells (59.7%), whereas heterochromia was present in only 39.5% of eyes and iris atrophy in 12.9% of eyes. In CMV-positive eyes, conversely, a higher incidence of ocular hypertension with markedly increased intraocular pressures above 30 mmHg (66.7%), keratic precipitates (81.0%), which were most commonly distributed in the center of the cornea (63.6%), an unaffected lens (55.0%), absent iris atrophy (100%), and absent posterior synechiae (90.5%) could be detected. This indicates a clinical presentation that was mainly compatible with Posner-Schlossman syndrome. In our cohort of RV-positive FUS patients, we saw a different cluster of clinical findings compared to the classification criteria suggested by the SUN Working Group. The main criteria, such as unilaterality, were mostly fulfilled. When applying all classification criteria, only 8.4% of 107 eyes and 10.5% of all 86 RV-positive eyes would qualify for the diagnosis of FUS. In addition, in our cohort of predominantly Caucasian patients, the clinical findings in patients with proven CMV infection differed from the clinical presentation typically associated with FUS.

Correlation of NUCB2/Nesfatin-1 with Cytokine Levels in Primary Open-Angle Glaucoma.

PURPOSE: Nesfatin-1 is produced in various tissues of the body including the hypothalamus. Neuroprotective properties of the neuropeptide hormone Nesfatin-1 were recently described. The aim of the study was to analyze the molecule Nesfatin-1 as a possible biomarker in POAG with neuroprotective properties pointing out the retinal-hypothalamic axis as target site in POAG and to obtain a molecular signature of cytokines in POAG as neuroinflammatory processes are a key factor of glaucoma development. METHODS: In this study, n=35 patients with moderate and advanced POAG (mean age 65.0y, IOP 13.9±3.0mmHg) and n=35 healthy controls (mean age 51.6y, IOP 14.3±2.7mmHg) were included. Clinical parameters including IOP, cup to disc ratio (CDR), glaucoma medication and retinal nerve fiber layer thickness (RNFL) were recorded. Plasma was collected for NUCB2/nesfatin-1 measurement using a Nesfatin-1 ELISA and for detection of 13 inflammatory cytokines using a multiplex bead-based immunoassay (MagPix). Multiple linear regression analysis was performed to adjust for confounding factors. RESULTS: Sex-independent or sex-dependent variables showed no significant differences in the Nesfatin-1 level (p>0.05). As a trend, an increase in NUCB2/nesfatin-1 in male glaucoma patients was found. Increased concentrations of 11 cytokines (GM-CSF, Interferon-γ, Interleukin-1ß, IL-2, 4, 5, 6, 7, 10, 12 and TNF-α) were detected in POAG. The female glaucoma patients demonstrated elevated cytokine concentrations compared to male patients. NUCB2/nesfatin-1 showed a significant correlation to IL-2 and IL-13 levels in POAG. Stepwise multiple regression analysis showed no difference in NUCB2/nesfatin-1 level between POAG and healthy controls after adjusting for sex and age (all p>0.05). CONCLUSION: As a trend, male POAG patients showed increased plasma NUCB2/nesfatin-1 levels. We further found inflammation as contributing factor to the pathogenesis of glaucoma, with a greater inflammatory response in women.

Behavior of SD-OCT Detectable Hyperreflective Foci in Diabetic Macular Edema Patients after Therapy with Anti-VEGF Agents and Dexamethasone Implants.

PURPOSE: Diabetic macular edema (DME) is the most common cause of blindness in the working-age population. Spectral-domain optical coherence tomography (SD-OCT) allows detection and monitoring of the edema and a detailed analysis of the retinal structure. Hyperreflective foci (HF) are small, circumscribed lesions on OCT, and their origin is yet to be determined. Our study was aimed to shed light on HF pathophysiology, by analyzing their number and location in DME patients at baseline and after therapy. METHODS: A prospective, observational study on 59 eyes of 51 DME patients who were treated with antivascular endothelial growth factor (VEGF) therapy (VEGF group, n = 40 eyes) or dexamethasone implant (DEX group, n = 19). HF and hard exudates (HE) were discriminated by their appearance on fundus photographs and their size on OCT. Quantity and location of HF and HE were analyzed at baseline and after therapy. RESULTS: DME decreased in 75% of patients in the VEGF (455.5 µm vs. 380.8 µm, p = 0.02) and in 95% of patients in the DEX group (471.6 µm vs. 381.9 µm, p = 0.007). The number of foci decreased in 62.5% of patients after anti-VEGF (130.6 vs. 111.1, p = 0.07) and in 68% of patients after dexamethasone injection ((123.4 vs. 94.9, p = 0.02) 5.1). A subgroup of 15% of eyes, all treated with anti-VEGF, showed accumulation of larger HF in outer retinal layers to visible HE during DME resolution, whereas smaller HF, found in all retinal layers, remained unchanged. There was a trend towards a dynamic shift of the foci from inner to outer retinal layers. CONCLUSION: The dynamic rearrangement of the small HF and their slightly greater reduction after anti-inflammatory therapy suggest inflammatory cells as their origin, whereas larger HF in the outer retinal layers correspond to microexudates. Furthermore, we found a more favourable outcome in patients with HF after treatment with dexamethasone implants compared to anti-VEGF agents.