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Cytomegalovirus (CMV) can cause recalcitrant recurrent keratouveitis and secondary glaucoma. We report a case of chronic recurrent anterior uveitis with secondary glaucoma presenting with acute visual loss and interface fluid 9 years after laser in situ keratomileusis. Based on clinical presentation, a viral aetiology was suspected. Aqueous tap was positive for CMV-DNA by real-time quantitative PCR of the aqueous humour. The patient was treated with systemic antivirals, topical corticosteroids and antiglaucoma medications. The interface fluid resorbed rapidly. The intraocular pressure (IOP) was controlled by trabeculectomy. There was no further corneal deterioration at 7-month follow-up and the IOP had also stabilised. We believe this is only the third reported case of CMV-related interface fluid syndrome. This case highlights the role of quantitative PCR analysis for establishing viral aetiology in recurrent unilateral hypertensive anterior uveitis and reports the unusual finding of interface fluid which resolved after starting systemic antiviral therapy.

Objective: A retinal vein occlusion (RVO) is a relatively common retinal vascular disorder, especially in the elderly. Many experiments have been performed on patients with an RVO but performing any type of experiments and especially longitudinal experiments on humans is difficult, if not impossible, on ethical grounds. Therefore, we have created a retinal vein occlusion (RVO) model by laser irradiation of cynomolgus monkeys after intravenous injection of rose bengal. We evaluated the pathological changes of the retina, and the effects of ranibizumab, an anti-vascular endothelial growth factor (VEGF) antibody, on the characteristics of the RVO. Methods: The integrity of the vascular system was evaluated by fluorescein angiography (FA), and the retinal thickness and volume were determined by optical coherence tomography (OCT). The cytokines and growth factors in the aqueous humour were identified by multiplex profiling. Results: Our results showed that ranibizumab decreased the degree of vascular leakage and retinal edema at 1-3 days (acute phase) and 3-7 days (subacute phase), and suppressed foveal thinning at 28-42 days (chronic phase) after the laser irradiation. Ranibizumab also decreased the area of the foveal avascular zone, and the area was negatively and significantly correlated with the thickness of the ganglion cell layer (GCL) complex. Furthermore, ranibizumab reduced the increased expression of VEGF in the aqueous humor, but did not affect the expressions of interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), angiopoietin-1 (ANG-1), or angiopoietin-2 (ANG-2). These findings suggest that ranibizumab attenuates the retinal edema and subsequent retinal atrophy in part by neutralizing VEGF. However, other cytokines and growth factors were also affected by the ranibizumab, which suggests that not only VEGF but also other unidentified agents might play a role in the pathogenesis of the RVO. Conclusion: We have created a non-human primate RVO model, which resembles the clinical RVO pathology. In this model, an injection of ranibizumab leads to a reduction in vascular leakage and the retinal thickness and volume by blocking the expression of VEGF. Our model might be useful for investigating the pathological mechanisms of RVOs and explore new therapeutic agents for RVO.

The aim of this study was to compare aqueous humour (AqH) cytokine profiles before and after Descemet’s membrane endothelial keratoplasty (DMEK) in eyes with bullous keratopathy (BK) and age-matched normal eyes. A total of 49 participants (mean age 75.0 ± 13.5 years) were divided into three groups: (1) BK patients scheduled for DMEK (BK group); (2) patients after DMEK (DMEK group; average postoperative time 1,018 ± 460 days); and (3) control participants without corneal endothelial disease scheduled for cataract surgery (control group). AqH (0.2 mL) was collected from all participants, and the levels of various AqH cytokines were simultaneously measured using a multiplex bead immunoassay. The DMEK group exhibited significantly lower concentrations of several pro-inflammatory cytokines, such as IL-1β, IL-5, IL-6, IL-10, and IL-8, and granulocyte colony stimulating factor than the BK group. In addition, the levels of IL-1β and IL-5 were significantly lower in the DMEK group than in the control group. The AqH levels of several pro-inflammatory cytokines were significantly reduced after DMEK, indicating that regeneration of the endothelial pump owing to the transplantation of a healthy endothelium might have a positive effect on anterior chamber inflammation.

The present study was designed to evaluate the age-related changes in biometal and antimicrobial peptide (cathelicidin) concentration and their role in oxidative cum pro-inflammatory cascade in an ovine animal model. Clinically healthy ovine (n = 126) were grouped as Group I (n = 55, age = up to 3 years), Group II (n = 52, age = above 3-below 6 years) and Group III (n = 19, age = 6 years above). Samples (aqueous humour and lens of the eye) were collected stored at - 80 °C till further analysis. In aqueous humour, the concentration of zinc (p

Purpose To evaluate long-term anatomical and functional outcomes of the MICOF keratoprosthesis to treat end-stage corneal blindness. Design Retrospective review of consecutive clinical case series. Participants Between October 2000 and October 2015, at the Department of Ophthalmology of Chinese PLA General Hospital (PLAGH), a total of 132 eyes of 131 patients had undergone a MICOF keratoprosthesis implantation. Of those, 91 eyes of 90 patients were included in this study. Methods Preoperative information, surgical procedures, and postoperative data were collected for each included eye. Main outcome measures Best-corrected visual acuity (BCVA), keratoprosthesis retention, and significant postoperative complications were reported. Results The most common indications for surgery were chemical or thermal burns (68.1%, 62 of 91 eyes) and explosive injury (12.1%, 11 of 91 eyes), followed by Stevens-Johnson Syndrome (10.0%, 9 of 91 eyes), Sjogren's syndrome (4.4%, 4 of 91 eyes), mucous membrane pemphigoid (3.3%, 3 of 91 eyes) and multi-penetrating keratoplasty failure (2.2%, 2 of 91 eyes). The mean follow-up duration was 8.38 ± 3.22 years (range: 5–17.25 years, median: 7.67 years). All patbients had a preoperative visual acuity of hand motions or worse. A MICOF keratoprosthesis significantly improved patients' visual function with bilateral end-stage corneal blindness. Postoperative visual acuity improved to 20/200 or better in 41 eyes (45.1%, of 91 eyes) and to 20/100 or better in 32 eyes (35.2% of 91 eyes) at the last follow-up visit. Preexisting glaucoma was present in 17 (18.7% of 91 eyes). The most common postoperative complications were overgrowth of the surface mucosa (31.9%, 29 of 91 eyes), glaucoma (25.3%, 23 of 91 eyes), retro-prosthetic membrane (15.4%, 14 of 91 eyes), keratoprosthesis device extrusion (15.4%, 14 of 91 eyes), superficial tissue thinning (14.3%, 13 of 91 eyes), endophthalmitis (13.2%, 12 of 91 eyes), titanium frame exposure (13.2%, 12 of 91 eyes), optical cylinder ante-displacement (13.2%, 12 of 91 eyes), cornea melting (7.7%, 7 of 91 eyes), retinal detachment (6.6%, 6 of 91 eyes) and aqueous humour leakage (2.2%, 2 of 91 eyes). 84.6% (77 of 91 eyes) of the eyes retained their initial keratoprosthesis at the latest follow-up. Conclusions A MICOF keratoprosthesis is a reliable approach to rescue vision in end-stage corneal blinded patients and has better retention than a Boston Kpro TypeⅡ.

BackgroundThis study investigates the association of intraocular cytokine expression and ultrawide-field fluorescein angiography (UWFA) quantitative imaging biomarkers and their association with angiographical feature response after antivascular endothelial growth factor (VEGF) therapy in diabetic macular oedema (DME).MethodsThe IMAGINE DME study is a post hoc imaging biomarker and intraocular cytokine assessment from the DAVE study, a prospective DME clinical trial that included aqueous humour sampling and UWFA imaging. Fifty-four cytokines associated with inflammation and angiogenesis were evaluated through multiplex arrays. UWFA parameters were assessed using an automated feature analysis platform to determine ischaemic and leakage indices and microaneurysm (MA) count. Eyes were classified into UWFA responder or non-responder groups based on longitudinal quantitative UWFA parameter improvement. Cytokine expression was correlated with UWFA metrics and evaluated in the context of therapeutic response.ResultsTwenty-one eyes were included with a mean age of 55±10 years. Increased panretinal leakage index correlated with VEGF (r=0.70, p=0.0005), angiopoietin-like 4 (r=0.77, p=4.6E-5) and interleukin (IL)-6 (r=0.64, p=0.002). Panretinal ischaemic index was associated with tissue inhibitor of metalloproteinases 1 (TIMP-1, r=0.49, p=0.03) and peripheral ischaemia correlated with VEGF (r=0.45, p=0.05). MA count correlated with increased monocyte chemotactic protein-4 (MCP-4, r=0.60, p=0.004) and platelet and endothelial cell adhesion molecule 1 (PECAM-1, r=0.58, p=0.005). Longitudinal MA reduction was associated with decreased baseline VEGF and urokinase receptor (uPAR) (pConclusionsBaseline and longitudinal quantitative UWFA imaging parameters correlated with multiple aqueous humour cytokine concentrations, including VEGF and IL-6. Further research is needed to assess the possible implications of using these findings for evaluating treatment response.

Background Cytomegalovirus (CMV) retinitis is a common opportunistic infection in patients with acquired immunodeficiency syndrome. The common funduscopic manifestations are haemorrhagic necrotising variety and granular variety. Frosted branch angiitis (FBA), as a special form, when it occurred after antiretroviral therapy(ART), could possibly be associated with immune reconstitution. We report a case of FBA secondary to CMV infection-associated unmasking immune reconstitution inflammatory syndrome (IRIS). Case presentation A 27-year-old man with human immunodeficiency virus infection developed FBA after 35 days of ART. The left Aqueous humour (AqH) tested positive for CMV DNA, and the patient was diagnosed with CMV retinitis. The degree of intraocular inflammation was reflected by increased levels of interleukin (IL)-6 and IL-8 in AqH. After anti-CMV treatment and continuous ART for several months, his FBA and vision significantly improved. CMV DNA became undetectable in the left AqH, and the IL-6 and IL-8 levels in AqH decreased. Conclusion FBA could be a sign of CMV-associated unmasking IRIS. Anti-CMV treatment alone or combination with steroid treatment may be administered, depending on the changes in CMV DNA load and immunologic profile of AqH.

Tingting Sun, 1,* Qingquan Wei, 1,* Peng Gao, 1,* Yongjie Zhang, 2 Qing Peng 1 1Department of Ophthalmology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, 200072, People’s Republic of China; 2Department of Human Anatomy, Nanjing Medical University, Nanjing, Jiangsu Province, 211166, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing PengDepartment of Ophthalmology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, 200072, People’s Republic of ChinaEmail pengqing@tongji.edu.cnYongjie ZhangDepartment of Human Anatomy, Nanjing Medical University, Nanjing, Jiangsu, 211166, People’s Republic of ChinaEmail zhangyongjie@njmu.edu.cnObjective: To investigate the concentrations of cytokine and chemokines profiling in aqueous humor for choroidal neovascularization (CNV) due to neovascular age-related macular degeneration (nAMD) before and during Intravitreal injection of ranibizumab (IVR) and its relation with the disease’s active state.Methods: The cytokine levels in aqueous humour were detected by the Bio-Plex® 200 System and the Bio-Plex™ Human Cytokine Standard 27-Plex, Group I. Aqueous humour samples of experimental group were collected from 19 patients diagnosed nAMD at baseline and at 1 month after IVR. Aqueous humour samples of control group were collected from 20 patients undergoing cataract surgery.Results: Aqueous humor levels of basic fibroblast growth factor (basic FGF) and RANTES were significantly lower in nAMD patients than in the control group (P=0.044 and P< 0.001, respectively). Vascular endothelial growth factor-A (VEGF-A) was significantly higher in nAMD patients than in the control group (P < 0.001). The average Eotaxin levels were significantly higher in nAMD patients after IVR than before (P=0.03). Contrarily, the average VEGF-A levels were significantly lower in AMD patients after IVR than before (P < 0.001).Conclusion: Angiogenic, growth factors and inflammatory are involved in the formation of neovascularization of AMD patients. IVR did not cause significant differences in any growth factors or inflammatory cytokines in nAMD patients with the exception of VEGF.Keywords: choroidal neovascularization, CNV, neovascular age-related macular degeneration, nAMD, ranibizumab, cytokines

PURPOSES: To elucidate the mechanism of intraocular pressure (IOP) reduction by microhook ab interno trabeculotomy (μLOT), the aqueous humour outflow facility was compared preoperatively and post-operatively. METHODS: Fifty-one eyes (37 patients; mean age, 67.2 ± 11.8 years) were included. The IOP, number of medications and outflow facility coefficient (C) estimated by pneumatonography were compared preoperatively and post-operatively using the paired t test. Linear regression analysis was performed to identify possible correlations between the C value and IOP or number of medications. To adjust for biases from including both eyes of a patient and differences in background, the preoperative and post-operative C values were compared using a mixed effects regression model. RESULTS: The mean preoperative IOP (18.2 mmHg) and mean number of medications (2.8) decreased significantly post-operatively by 26% and 18%, respectively, to 13.5 mmHg and 2.3 (p

ObjectiveTo investigate the concordance between aqueous and vitreous tap culture results among different types of bacterial endophthalmitis.Methods and analysisThis retrospective cohort analysis included all cases diagnosed with endophthalmitis at Moorfields Eye Hospital between January 2008 and March 2020. Aqueous and vitreous samples obtained simultaneously at presentation. Samples were evaluated for sensitivity, specificity, negative and positive predictive values.ResultsA total of 217 patients (217 eyes) were included in the study. Postsurgical endophthalmitis was the most common type of endophthalmitis and diagnosed in 35.9% of the cases. The rate of positive culture results was 32.2% from vitreous tap and 21.7% from aqueous tap. The culture yield through vitreous sampling was 15.7% when aqueous culture results were negative, and in 5.1%, the aqueous sample was positive when the vitreous tap results were negative. Considering the vitreous tap as the gold standard, aqueous sample culture results showed a statistically significant high specificity and positive predictive values in cases of postsurgical endophthalmitis, late-onset endophthalmitis associated with glaucoma procedures, postintravitreal injection and endophthalmitis associated with bacterial keratitis. Coagulase Negative Staphylococcus was the most common organism isolated from vitreous and aqueous samples.ConclusionsEven though the sensitivity and specificity of aqueous tap are low, our results show that in a few cases it identified important organisms, otherwise missed by vitreous sampling alone. Culture of vitreous sample remains the gold standard for isolation of pathogen in bacterial endophthalmitis, but aqueous samples should also be obtained as an adjunct for the diagnosis.

Primary open‐angle glaucoma (POAG) is characterized by irreversible neurodegeneration accompanied by visual field defects and high intraocular pressure. Currently, an effective treatment is not available to prevent the progression of POAG, other than treatments to decrease the high intraocular pressure. We performed proteomic analysis of aqueous humour (AH) samples from patients with POAG combined with cataract and patients with cataract to obtain a better understanding of the pathogenesis of POAG and explore potential treatment targets for this condition. Samples were collected from 10 patients with POAG combined with cataract and 10 patients with cataract. Samples from each group were pooled. A high‐resolution, label‐free, liquid chromatography‐tandem mass spectrometry‐based quantitative proteomic analysis was performed. In total, 610 proteins were identified in human AH samples from the two groups. A total of 48 up‐regulated proteins and 49 down‐regulated proteins were identified in the POAG combined with cataract group compared with the control group. Gene Ontology (GO) analysis revealed key roles for these proteins in inflammation, immune responses, growth and development, cellular movement and vesicle‐mediated transport in the biological process category. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated the down‐regulated expression of glutathione S‐transferase P (GSTP1) in the glutathione metabolism signalling pathway in the POAG combined with cataract group. Additionally, certain significantly differentially expressed proteins in the proteomic profile were verified by enzyme‐linked immunosorbent assay (ELISA). GSTP1 levels were reduced in the human AH samples from the POAG combined with cataract group, based on the results of ELISA and proteomic profiling. Therefore, GSTP1, a redox‐related marker, may be involved in the pathological process of POAG and may become a treatment target in the future.

The eye, like all organs, is exposed to the effects of the body's endocrine system. In addition, however, local branches of the endocrine system control important organ-specific functions, such as the production and drainage of aqueous humour. Similarly, the eye as a sensory organ acts back on endocrine controlled functions of the body, for example the day-night rhythm. This article aims to illustrate the physiological and pathological interactions of the eye and the endocrine functions of the body in the context of glaucoma. 1. The renin-angiotensin-aldosterone system, which as a local system is involved in the control of aqueous humour production and outflow. 2. The hormone endothelin, which as a strong vasoconstrictor plays a role in the dysregulated perfusion of the optic nerve and retina, and 3. the disruption of the day-night rhythm in advanced glaucoma, which is thought to be caused by damage to light-sensitive ganglion cells.Das Auge ist, wie alle Organe, den Wirkungen des endokrinen Systems des Körpers ausgesetzt. Darüber hinaus steuern aber im Auge, wie in anderen Organen, lokale Ableger endokriner Systeme wichtige organspezifische Funktionen, z. B. die Produktion und den Abfluss des Kammerwassers. Gleichermaßen wirkt das Auge als sensorisches Organ auf endokrin gesteuerte Funktionen des Körpers zurück, bspw. auf den Tag-Nacht-Rhythmus. Dieser Artikel soll anhand von 3 Themengebieten die physiologischen und pathologischen Wechselwirkungen von Auge und endokrinen, teils auch auto- und parakrinen Funktionen des Körpers im Kontext des Glaukoms darstellen: 1. Das Renin-Angiotensin-Aldosteron-System, das als lokales System an der Steuerung von Kammerwasserproduktion und -abfluss beteiligt ist. 2. Das Hormon Endothelin, welches als starker Vasokonstriktor eine Rolle bei der fehlregulierten Perfusion von Sehnerv und Retina spielt, und 3. die Störung des Tag-Nacht-Rhythmus bei fortgeschrittenem Glaukomstadium, der vermutlich eine Schädigung lichtsensitiver Ganglienzellen zugrunde liegt.

BackgroundA single application of JV-GL1 substantially lowers non-human primate intraocular pressure (IOP) for about a week, independent of dose. This highly protracted effect does not correlate with its ocular biodisposition or correlate with the once-daily dosing regimen for other prostanoid EP2 receptor agonists such as trapenepag or omidenepag. The underlying pharmacological mechanism for the multiday extended activity of JV-GL1 is highly intriguing. The present studies were intended to determine EP2 receptor involvement in mediating the long-term ocular hypotensive activity of JV-GL1 by using mice genetically deficient in EP2 receptors.MethodsThe protracted IOP reduction produced by JV-GL1 was investigated in C57BL/6J and EP2 receptor knock-out mice (B6.129-Ptger2tm1Brey/J; EP2KO). Both ocular normotensive and steroid-induced ocular hypertensive (SI-OHT) mice were studied. IOP was measured tonometrically under general anaesthesia. Aqueous humour outflow facility was measured ex vivo using iPerfusion in normotensive C57BL/6J mouse eyes perfused with 100 nM de-esterified JV-GL1 and in SI-OHT C57BL/6J mouse eyes that had received topical JV-GL1 (0.01%) 3 days prior.ResultsBoth the initial 1-day and the protracted multiday effects of JV-GL1 in the SI-OHT model for glaucoma were abolished by deletion of the gene encoding the EP2 receptor. Thus, JV-GL1 did not lower IOP in SI-OHT EP2KO mice, but in littermate SI-OHT EP2WT control mice, JV-GL1 statistically significantly lowered IOP for 4–6 days.ConclusionsBoth the 1-day and the long-term effects of JV-GL1 on IOP are entirely EP2 receptor dependent.

Purpose High intensity focused ultrasound (HiFU) is a cyclodestructive therapy for controlling intraocular pressure (IOP) in glaucoma. The mechanism of action is thought to be through destruction of the ciliary epithelium as well as increased uveoscleral outflow. We reviewed the change in aqueous humour dynamics parameters including aqueous humour flow rate, tonographic outflow facility (TOF) and uveoscleral outflow at 12 months. Patients and methods This is a prospective observational study. Consecutive patients with open angle glaucoma (OAG) or ocular hypertension (OHT) requiring further IOP lowering were enroled in the study between August 2016 and January 2017. Patients were commenced on medication washout period prior to baseline and twelve months' visit. Results Sixteen patients (OAG) in the treatment group underwent assessment at twelve months follow up. Mean age was 63.1 ± 11 years. Eleven patients were African/Caribbean and 5 were Caucasian. Nine patients were female and 7 were male. Mean post-washout IOP was reduced by 21% (28.3 ± 5.7 at baseline vs 22.4 ± 8.4 mmHg at 12 months, p = 0.04). Aqueous humour flow rate was reduced by 16% at twelve months (2.40 ± 0.6 at baseline vs 2.02 ± 0.6 µl/min at 12 months, p = 0.0493). There was no statistically significant change in the TOF (0.12 ± 0.09 at baseline vs 0.08 ± 0.05 µl/min/mmHg at 12 months, p = 0.08) or uveoscleral outflow (0.6 ± 1.3 at baseline vs 1.3 ± 0.85 µl/min at 12 months, p = 0.15). Conclusion In this study, we demonstrated that the observed IOP reduction was likely due to aqueous humour flow rate reduction. The TOF and uveoscleral outflow were not detectibly changed.

Purpose: To introduce a rare case of patient with hyperlipidemic myeloma and ocular manifestation in the form of masquerade syndrome with acute elevation of intraocular pressure (IOP) and hyperviscous retinopathy. Results: 55-year-old man with newly diagnosed hyperlipidemic myeloma and hyperviscous syndrome was acutely referred to our glaucoma outpatient clinic due to problems with his left eye: sudden pain, blurred vision, redness of the eye and IOP of 44 mm Hg. We excluded attack of angle closure glaucoma and found the presence of whitish material in the anterior chamber and blood obstructing the iridocorneal angle. Glaucoma therapy was initiated and lavage of the anterior chamber of the left eye with sampling of the aqueous humour for biochemical and cytological examination was performed. Identification of trace amount of cryoprotein in the samples of humour proved diagnosis of masquerade syndrome. Finding of the hyperviscous retinopathy and nonperfusion of wide peripheral areas of retina in both eyes was indicated to laser coagulation of these areas. The patient underwent in the meantime three times plasmapheresis, four cycles of biological therapy and autologous stem cell transplantation reaching complete remission of the myeloma. Local and systemic therapy led to significant clinical finding improvement on the anterior segment and fundus of both eyes. Conclusions: Masquerade syndrome can be complicated by acute elevation of IOP. Diagnostic lavage of the anterior chamber, local therapy, systemic therapy and close interdisciplinary cooperation contributed to right diagnosis, IOP normalisation, ocular and general condition improvement.

Elevated intraocular pressure (IOP) is the primary risk factor for blindness in glaucoma. IOP is determined by many factors including aqueous humour production and aqueous humour outflow (AHO), where AHO disturbance represents the primary cause of increased IOP. With the recent development of new IOP lowering drugs and Minimally Invasive Glaucoma Surgeries (MIGS), renewed interest has arisen in shedding light on not only how but where AHO is occurring for the trabecular/conventional, uveoscleral/unconventional, and subconjunctival outflow pathways. Historical studies critical to understanding outflow anatomy will be presented, leading to the development of modern imaging methods. New biological behaviours uncovered by modern imaging methods will be discussed with relevance to glaucoma therapies emphasized.摘要: 升高的眼内压 (intraocular pressure, IOP)是青光眼致盲的首要危险因素。IOP取决于房水产生及房水流出 (aqueous humour outflow, AHO) 等诸多因素, 其中AHO障碍为导致IOP升高的首要原因。随着近年来新的降眼压药及青光眼微创手术 (Minimally Invasive Glaucoma Surgeries, MIGS) 的发展, 人们不仅对对阐明小梁/传统、葡萄膜巩膜/非传统和结膜下流出道的AHO方式也对其部位产生了新的兴趣。历史研究的关键是阐明流出通道解剖, 为现代影像技术发展奠定基础。本文将讨论青光眼治疗与现代影像学方法所揭示的新的生物学行为的相关性。.

Background/AimsThe current study evaluates the efficacy and safety of the stand-alone implantation of the MINIject (iSTAR Medical, Wavre, Belgium) supraciliary, microinvasive glaucoma drainage device in patients with medically uncontrolled open-angle glaucoma.MethodsThis prospective, multicentre, first-in-human, single-arm interventional study evaluated stand-alone, ab interno implantation in 25 patients of a 5 mm long uveoscleral device made of STAR biocompatible material, which is a soft, microporous, flexible silicone. The primary outcome was the reduction of intraocular pressure (IOP) at 6 months compared with baseline, and follow-up continued until 2 years for 21 patients. Secondary outcomes included success defined as diurnal IOP of ≤21 mmHg and >5 mmHg with an IOP reduction of 20% without (complete) or with/without (qualified) glaucoma medication.ResultsMean baseline IOP was 23.2±2.9 mmHg on 2.0±1.1 glaucoma medication ingredients and decreased to 13.8±3.5 mmHg (−40.7% reduction) on 1.0±1.3 medications 2 years after implantation. Complete success was achieved in 47.6% of patients (10/21) and qualified success in 100% of patients (21/21) at the 2-year follow-up. All patients achieved a 20% IOP reduction with 48% of patients medication-free. No serious ocular adverse events or additional glaucoma surgery were reported. Mean central endothelial cell density (ECD) mildly decreased from 2411 cells/mm2 (n=26) to 2341 cells/mm2 (n=21) at 24 months, which represents a 5% decrease for matched eyes. No patient had a ≥30% decrease in central ECD.ConclusionThis first-in-human study on the stand-alone implantation of the MINIject supraciliary drainage system shows promising IOP-lowering results and medication reduction over 24 months with few adverse events.Trial registration numberNCT03193736.

Glaucoma is an irreversible condition resulting from the increase in intraocular pressure (IOP); which leads to permanent loss of vision with the destruction of retinal ganglion cells (RGCs). The IOP elevations are controlled in normal by the physiological flow of aqueous humour. A population with age above 40 is more susceptible to glaucoma. Other factors like gender, genetics, race etc. plays major roles in the development of the disease. Current treatment methods available for the disease includes drugs come under the classes of beta receptor blockers, carbonic anhydrase inhibitors, cholinergic agonists, prostaglandins etc. N-methyl-D-aspartate (NMDA) antagonists, inducible nitric oxide synthase (iNOS) inhibition, cytoskeletal agents, Rho-kinase inhibitors etc are few novel targets sites which are in research focus for the treatment of the disease. Developments in nanomedicine are also being evaluated for their potential in treating the growing glaucomatous population. Nanosystems are suggested to avoid the difficulties in tackling the various ocular barriers to a limit, help to decrease the instillation frequency of topical medication and can provide drug delivery in a sustained or controlled manner. This review focuses on the current and emerging treatment methods for glaucoma along with some of the nanoformulations for ocular drug delivery.

The mechanism of diabetes and cataracts is complicated. Considering our increasing acknowledge of exosomes, exosomal miRNAs isolated from aqueous humour (AH) may play an important role in the mechanism of diabetes and cataracts. Our study aimed to isolate exosomes from human aqueous humour and study the functions of exosomal miRNAs on human lens epithelial cells (HLECs).MiRNA sequencing revealed that 295 miRNAs were upregulated and 138 miRNAs were downregulated in exosomes of the diabetes and cataracts group (DMC) compared with the age-related cataracts group (ARC), among which miR-551b was highly expressed with a log2 fold change of 5.99. GO and KEGG analyses indicated that the predicted genes were mainly involved in cadherin binding, proteoglycans in cancer and AGE-RAGE signalling pathway in diabetic complications. We then examined the function of miR-551b and found that miR-551b reduced the viability and increased the apoptosis of HLECs by downregulating CRYAA expression.Exosomes isolated from human aqueous humour contained abundant miRNAs. A highly expressed miRNA, miR-551b, could regulate the functions of HLEC by targeting CRYAA.We pooled all the aqueous humour of each group into one sample and isolated exosomes from human aqueous humour by ultracentrifugation, measured the size and concentration of exosomes by nanoparticle tracking analysis (NTA), observed the morphology of exosomes by transmission electron microscopy (TEM), and sequenced exosomal miRNAs. We performed bioinformatic analysis of the sequencing results, including GO analysis and KEGG pathway enrichment. We then examined CRYAA mRNA expression levels and protein levels by quantitative real-time PCR and Western blot. Cell Counting Kit-8 and flow cytometry were applied to examine cell viability, proliferation and apoptosis.

Importance Age-related cataract is the leading cause of blindness worldwide. The pathological mechanisms causing this disease remain elusive. Background To examine the involvement of uric acid (UA) in the pathogenesis of posterior subcapsular cataract (PSC). Design Retrospective study and experimental investigation. Participants A total of 180 patients with PSC or non-PSC were included. Methods Samples obtained from the patients were used to analyse content of UA and for histochemical examinations. The effects of UA on human lens epithelial cells were also investigated. Main outcome measures Aqueous humour UA and urate deposits. Results The results showed a significant increase of aqueous humour UA in patients with PSC. After adjustment for potential confounders, elevated aqueous humour UA (odds ratio [OR] = 1.45) showed a stronger association with PSC than serum UA (OR = 1.10). Gomori methenamine silver staining revealed in PSC an intense deposit of urates in the lens fibres in equatorial regions, and in subcapsular fibres in posterior regions of the lens. Such staining was not detected in the lens with non-PSC. Treatment with UA-induced senescence and apoptosis in human lens epithelial cells in a dose dependent manner. Our results suggest that the elevated level of UA in aqueous humour causes a deposition of urates in human lens epithelium, which could possibly lead to dysfunction of these cells that generates opacification in PSC. Conclusions and relevance These findings indicate the local action of excessive UA in the pathogenesis of PSC. Control of serum UA level could delay the progression of PSC.

Objective This study aimed to perform genotyping of Toxoplasma gondii strain or variant causing atypical toxoplasmic uveitis in Indonesian patients. Methods Ocular fluid samples originating from 46 uveitis patients with non-specific ocular manifestations were analysed for Toxoplasma infection by PCR of the B1 locus. The clonal type was determined by amplification, sequencing and phylogenetic analysis of SAG2 and GRA6 loci in B1-positive samples. Clinical data were obtained from the medical records. Results Pan uveitis was the most frequent manifestation (65.2%) and mostly unilateral (76.1%). PCR of the B1 locus identified eight positive subjects (12.5%); six had panuveitis and two of these had diabetes mellitus. Phylogenetic analysis with maximum likelihood of the SAG2 locus in the B1-positive samples resulted in Toxoplasma gondii SAG2 type III allele. No positive result was obtained from the PCR of GRA6 locus. Conclusion Toxoplasma gondii SAG2-type III allele was identified in an atypical presentation of toxoplasmic uveitis in Indonesia.

Background/Aims To investigate whether the association of long-term intraocular pressure (IOP) fluctuation with the rate of progression of normal-tension glaucoma (NTG) differs between myopia and non-myopia. Methods The medical records of 65 myopic NTG (axial length (AL) > 24.0 mm) and 64 non-myopic NTG eyes (AL Results The average follow-up period was 8.3 years. Twenty-two (22) non-myopic eyes (34.4%) and 27 myopic eyes (41.5%) showed NTG progression (p=0.511). The interaction of myopia with IOP fluctuation was a significant factor regarding both MD and VFI slope (p=0.002, 0.024, respectively); stratified analyses suggested that the risk effect of IOP fluctuation was significant only in myopic NTG in terms of both MD (β= −1.27, p=0.003) and VFI slope (β=−2.32, p=0.011). Conclusion Long-term IOP fluctuation was significantly related to faster visual field progression in myopic NTG eyes, compared with non-myopic NTG eyes.

Objective To characterize the total intraocular aqueous humour antibody profiles in cases receiving anti-vascular endothelial growth factor (anti-VEGF) for retinal vascular disease compared with controls without retinal pathology. Design Cross-sectional. Participants 93 aqueous humour samples: 22 eyes undergoing cataract surgery (controls) and 71 eyes receiving intravitreal injections (IVI) (cases) for macular edema or neovascularization. Methods Antibody isotyping of aqueous humour was performed using Milliplex MAP Human Isotyping Multiplex Assay. Cases and controls were compared for several outcome measures. Results The primary outcome measure was total mean antibody isotype concentration quantified in the aqueous humour. Secondary outcomes included comparing aqueous humour concentrations with visual acuity, number of IVI received, type of anti-VEGF agent injected, and persistence intra-/subretinal fluid post injection. Mean immunoglobulin M (IgM) concentrations in cases were 19-fold higher compared with controls. Aqueous immunoglobulin G (IgG)1,2,3,4 and immunoglobulin A (IgA) were 2–4-fold higher in cases compared with controls. Disease-specific trends were observed, with diabetic retinopathy (DR) eyes containing the highest amounts of aqueous antibodies. Total number of injections correlated with higher titres of IgG1 (p Conclusions Intraocular antibodies are present in the aqueous humour at significantly higher concentrations in eyes receiving IVIs for retinal vascular diseases compared with controls.

Glaucoma is well-known clinical eye conditions that damage the optic nerve due to abnormal pressure conditions in eye. Hesperidin is well-known glycoside widely present in the citrus fruits, and its aglycone form is known as hesperetin. Hesperidin is major flavone found in orange fruits. Hypotensive effect of hesperidin in acute and chronic glaucoma rats, glutamate level in vitreous humour and glutathione (GSH) level in aqueous humour were determined following 25, 50 and 100 mg/kg of hesperidin treatment. Acetazolamide (5 mg/kg) was used as positive control. Hesperidin treatment significantly reduced the increased intraocular pressure (IOP) level in dextrose induced ocular hypertension than saline treated rats. The effect of hesperidin was comparable to the positive control acetazolamide. Similarly, hesperidin treatment significantly reduced the IOP level in prednisolone acetate induced ocular hypertension than saline treated rats. In the aqueous humour, hesperidin treatment increased the glutathione level 125%, 184.4% and 231.2% at 25, 50 and 100 mg/kg of hesperidin respectively. In the vitreous humour, hesperidin treatment reduced the glutamate level 9.9%, 13.2% and 25.3% at 25, 50 and 100 mg/kg of hesperidin respectively. Histopathological analysis of normal saline treated rats showed morphological alteration in ciliary bodies. However, rats treated with hesperidin showed the reduced level of morphological alteration in ciliary bodies. Taking all these data together, it is suggested that the hesperidin supplementation was effective against glaucoma in experimental rats.

Purpose To evaluate the penetration of levofloxacin and dexamethasone sodium phosphate into the aqueous humour (AH) after administration in combination and as single molecules. Evaluation of the penetration of those agents in the site of action and their pharmacodynamic potential activity in view of the intended clinical use after cataract surgery. Methods Randomised, assessor-blinded, parallel-group. Patients scheduled for cataract surgery were assigned in a 1:1:1 ratio to: levofloxacin + dexamethasone sodium phosphate (L-DSP), Levofloxacin (L) or Dexamethasone sodium phosphate (DSP) eye drops. Either test or reference drugs were instilled in the cul-de-sac twice, 90 and 60 min before paracentesis. Results A total of 125 patients completed the study. Fraction of dose absorbed in the anterior chamber was 3.8–4.2 · 10−4 for levofloxacin and 0.3–0.4 · 10−4 for dexamethasone, respectively. No notable differences in concentration of levofloxacin were found between L-DSP arm (1.970 nmol/ml) and L arm (2.151 nmol/ml). The concentrations of levofloxacin were well above the MICs for the most frequent Gram-positive and Gram-negative eye pathogens. Dexamethasone concentrations were slightly lower in L-DSP arm (0.030 nmol/ml) than in DSP arm (0.042 nmol/ml), but still in the pharmacodynamically active range in the site of action. The difference was not clinically relevant. DSP was not detected in any HA sample, suggesting its full hydrolysis to free dexamethasone. Conclusion Our results confirm that no interaction is evident on the corneal penetration of levofloxacin and dexamethasone which reach pharmacologically active concentrations when instilled as fixed combination eye drops to patients undergoing cataract surgery. Trial registration ClinicalTrials.gov Identifier: NCT03740659

IMPORTANCE Micro-RNAs (miRNAs) have been studied as new biomarkers or mediators in various diseases, but the value of aqueous humour (AH) miRNAs in diabetic macular oedema (DMO) is still not known. BACKGROUND To compare AH miRNAs and related cytokine expression in DMO patients and healthy controls. DESIGN Prospective cross-sectional study. PARTICIPANTS Twenty naive DMO patients and 13 control subjects, who were scheduled for intravitreal injection and cataract surgery, respectively. METHODS AH samples were collected at the beginning of each procedure and analysed using a miRNA polymerase chain reaction (PCR) array composed of 84 miRNAs, reverse transcripase-quantitative PCR (qPCR) for verifying selected differentially expressed miRNAs, and a cytokine assay, the results of which were compared with bioinformatics conducted to find out genes associated with DMO-related miRNAs. MAIN OUTCOMES MEASURES AH expression of miRNAs and cytokines and the bioinformatics results. RESULTS Five miRNAs (hsa-miR-185-5p, hsa-miR-17-5p, hsa-miR-20a-5p, hsa-miR-15b-5p and hsa-miR-15a-5p) showing a fold change greater than -50 in log2 values in the miRNA PCR array were selected, all significantly down-regulated in the DMO group compared to the control group (P

Glaucoma patients often require long-term or even lifelong medical antiglaucomatous treatment. Benzalkonium chloride (BAK) is the most frequently used preservative in medical glaucoma treatment. Laser flare photometry is the noninvasive quantitative measurement of anterior chamber protein level and helps tracking intraocular inflammation. The purpose of our study was to evaluate the ocular aqueous humour flare in glaucoma patients, scheduled for cataract surgery without any other ocular diseases, and the association with pseudoexfoliation (PEX) syndrome, number of medications used, and BAK. A prospective case-control age- and gender-matched study, including open-angle glaucoma patients (>2 years of treatment) with cataract, matched with cataract patients with no other ocular pathology (control group). We found that the aqueous humour flare was higher in the glaucoma group than in the control group. PEX syndrome increased the aqueous humour flare independently from glaucoma diagnosis. The number of used antiglaucomatous medications correlated moderately with the aqueous humour flare. The BAK index showed weak positive correlation with aqueous humour flare. A variety of factors can affect aqueous humour flare increase, including PEX syndrome, medical substance used to treat glaucoma, number of different medications, and presence of BAK. The combination of these factors is of key importance to long-term glaucoma treatment.

Background The aim of this study was to compare the distribution characteristics and ocular pharmacokinetics of norvancomycin (NVCM) in ocular tissues of the anterior segment between continuous topical ocular instillation and hourly administration of eye drop in rabbits. Methods Sixty rabbits were randomly divided into two groups: continuous topical ocular instillation drug delivery (CTOIDD) group and eye drop (control) group. In the CTOIDD group, NVCM solution (50 mg/mL) was perfused to the ocular surface using the CTOIDD system at 2 mL/h up to 10 h and the same solution was administered at one drop (50 μL) per hour for 10 h in the control group. Animals (N=6 per time-point per group) were humanely killed at 2, 4, 6, 10, and 24 h to analyze their ocular tissues and plasma. The concentrations of NVCM in the conjunctiva, cornea, aqueous humour, iris, ciliary body and plasma were measured by HPLC with photodiode array detector. The pharmacokinetic parameters were calculated by Kinetica 5.1. Results The highest concentrations of NVCM for the CTOIDD group and control group were 2105.45±919.89 μg/g and 97.18±43.14 μg/g in cornea, 3033.92±1061.95 μg/g and 806.99±563.02 μg/g in conjunctiva, 1570.19±402.87 μg/g and 46.93±23.46 μg/g in iris, 181.94±47.11 μg/g and 15.38±4.00 μg/g in ciliary body, 29.78±4.90 μg/mL and 3.20±1.48 μg/mL in aqueous humour, and 26.89±5.57 μg/mL and 1.90±1.87 μg/mL in plasma, respectively. The mean NVCM levels significantly increased at all time-points in cornea, iris, and ciliary body (p, Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/mh0eyzHYgRE

Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide which unfortunately has no known effective cure to date. Despite many clinical trials indicating the effectiveness of preclinical treatment, a sensitive tool for screening of AD is yet to be developed. Due to multiple similarities between ocular and the brain tissue, the eye is being explored by researchers for this purpose, with utmost attention focused on the retinal tissue. Besides visual functional impairment, neuronal degeneration and apoptosis, retinal nerve fiber degeneration, increase in the cup-to-disc ratio, and retinal vascular thinning and tortuosity are the changes observed in the retinal tissue which are related to AD. Studies have shown that targeting these changes in the retina is an effective way of reducing the degeneration of retinal neuronal tissue. Similar mechanisms of neurodegeneration have been demonstrated in the brain and the eyes of AD patients. Multiple studies are underway to investigate the potential of diagnosing AD and detection of amyloid-β (Aβ) levels in the retinal tissue. Since the tissues in the anterior segment of the eye are more accessible for in vivo imaging and examination, they have more potential as screening biomarkers. This article provides a concise review of available literature on the ocular biomarkers in anterior and posterior segments of the eye including the cornea, aqueous humour (AH), crystalline lens, and retina in AD. This review will also highlight the newer technological tools available for the detection of potential biomarkers in the eye for early diagnosis of AD.

Key points An elevation in intracranial pressure (ICP) lowers conventional outflow facility (increases aqueous outflow resistance) of rat eyes. The reduction in outflow facility correlates with an increase in intraocular pressure (IOP). The effect of ICP elevation on outflow facility and IOP is blocked by TTX. The results indicate that aqueous humour dynamics is modulated by ICP-driven neural feedback from the brain. This feedback mechanism may act to stabilize translaminar pressure across the optic nerve head and may provide a new avenue for glaucoma therapy. Abstract While intraocular pressure (IOP) is a well-known risk factor for glaucoma, intracranial pressure (ICP) is attracting heightened interest because of its influence on optic nerve head biomechanics. Studies have shown that ICP can have marked impacts on posterior eye health by modifying the translaminar pressure gradient across the optic nerve. There is also growing evidence that IOP and ICP may be interconnected, although the mechanism of their putative interaction is unknown. We sought to test the hypothesis that ICP modulates IOP by altering aqueous humour dynamics. The anterior chamber and lateral ventricle of anaesthetized Brown-Norway rats were cannulated with fine-gauge needles connected to a programmable pump and saline reservoir, respectively. ICP was manipulated by varying reservoir height, and eye outflow facility (C) was determined from the pump flow rate required to hold IOP at different levels. C was 22 ± 4 nl/min/mmHg at resting ICP and 13 ± 3 nl/min/mmHg when ICP was raised 15 mmHg, a reduction of 41 ± 13% (n = 18). The decrease in outflow facility was independent of blood pressure, reversible, scaled with ICP elevation and correlated with increases in resting IOP. It was physiological in origin because C returned to baseline values after the rats were killed and corneal application of TTX though ICP remained elevated. These results indicate that a neural feedback mechanism driven by ICP regulates conventional outflow facility in rats. The mechanism may protect the eye from translaminar pressure swings and may offer a new target for glaucoma treatment.

This chapter describes the anatomy of the eyeball, the visual pathway, and the ocular adnexae. It also provides a basic introduction to the physiology and functioning of the eye.

Acute angle closure is an emergent ophthalmic condition that develops as a result of an obstructed outflow of aqueous humour between the anterior and posterior chambers of the eye, leading to a sudden rise in intraocular pressure and secondary optic neuropathy if left untreated. The most common primary cause is a pupillary block in patients with pre-existing narrow angles, such as those who are long-sighted. However, awareness should be raised to identify secondary causes of angle closure, including the use of commonly prescribed medications. A detailed interrogation is essential to exclude other possible confounding disorders that present similarly, especially those originating in the CNS. Angle closure should be excluded in all patients presenting with sudden onset of red eye associated with pupillary dilation, dull pain and headache. Basic examination of the eye should include assessment of the anterior segment with a bright light, measurement of intraocular pressure and a full neurological exam. Immediate treatment must be initiated whenever there is high clinical suspicion of acute angle closure, with the administration of systemic ocular hypotensive therapy to prevent damage to the optic nerve and limit visual loss. An urgent referral to the ophthalmologist is mandatory to dictate definitive management.

Purpose This study aimed to investigate the concentrations of cytokines and chemokines in diabetic macular edema (DME) eyes before and during therapy with the intravitreal injection of conbercept (IVC) and to identify associations with disease activity. Methods The Bio-Plex® 200 System and the Bio-PlexTM Human Cytokine Standard 27-Plex, Group I (Bio-Rad, Hercules, California, USA) were used to detect cytokine levels in aqueous humour. Experimental aqueous humour samples were collected from 18 patients with DME at the same time that IVC was performed at baseline and at 1 month. Control aqueous humour samples were collected from 16 patients undergoing cataract surgery. Results Significantly higher concentrations of vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), IL-8, eotaxin, granulocyte colony stimulating factor (G-CSF), interferon gamma-induced protein 10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1) were found in the aqueous humour of DME patients than cataract patients. One month after IVC, the intraocular concentrations of VEGF were significantly lower in the eyes of DME patients than at baseline. No other cytokines were significantly altered by conbercept therapy. Best-corrected visual acuity (BCVA) slightly improved following IVC compared with that at baseline, although this difference was not significant, and central macular thickness (CMT) significantly decreased 1 month after IVC treatment. Conclusion Angiogenic, inflammatory and growth factors are involved in the development of DME. With the exception of VEGF, IVC did not cause significant differences in any inflammatory cytokines or growth factors in DME patients. CMT is related to VEGF levels in aqueous humour.

International audience; PurposeTo conduct a systematic review and meta-analysis on the levels of oxidative stress markers and antioxidants in keratoconus compared to healthy subject.MethodThe PubMed, Cochrane Library, Embase, Science Direct and Google Scholar databases were searched on 1st June 2020 for studies reporting oxidative and antioxidative stress markers in keratoconus and healthy controls. Main meta-analysis was stratified by type of biomarkers, type of samples (tears, cornea, aqueous humour and blood) and type of corneal samples (stromal cells, epithelium and endothelium).ResultsWe included 36 articles, for a total of 1328 keratoconus patients and 1208 healthy controls. There is an overall increase in oxidative stress markers in keratoconus compared with healthy controls (standard mean deviation (SMD) = 0.94, 95% confidence interval (95% CI) 0.55–1.33), with a significant increase in reactive oxygen and nitrogen species (1.09, 0.41–1.78) and malondialdehyde (1.78, 0.83–2.73). There is an overall decrease in antioxidants in keratoconus compared with healthy controls (−0.63, −0.89 to −0.36), with a significant decrease in total antioxidant capacity/status (−1.65, −2.88 to −0.43), aldehyde/NADPH dehydrogenase (−0.77, −1.38 to −0.17), lactoferrin/transferrin/albumin (−1.92, −2.96 to −0.89) and selenium/zinc (−1.42, −2.23 to −0.61). Oxidative stress markers were higher in tears and in cornea of keratoconus than in aqueous humour, and antioxidants were decreased in tears, aqueous humour and blood without difference between sample type. Oxidative stress markers increased in stromal cells and antioxidants decreased in endothelium.ConclusionOxidative stress markers and antioxidants were dysregulated in keratoconus, involving an imbalance of redox homeostasis in tears, cornea, aqueous humour and blood.

Dry eye disease (DED) is a multifactorial disease that manifests in patients with a variety of symptoms and signs such as ocular pain, visual issues, rapid tear evaporation and/or decreased tear production. It is a global health problem and is the leading cause of optometry and ophthalmology clinic visits. The mainstay therapy for DED is artificial tears (ATs), which mimics tears and improves tear stability and properties. ATs have been found to improve symptoms and signs of disease in all DED subtypes, including aqueous deficient DED and evaporative DED. However, given the heterogeneity of DED, it is not surprising that ATs are not effective in all patients. When AT fails to relieve symptoms and/or signs of DED, it is critical to identify the underlying contributors to disease and escalate therapy appropriately. This includes underlying systemic diseases, meibomian gland dysfunction, anatomical abnormalities and neuropathic dysfunction. Thus, this review will discuss the benefits and limitations of ATs and review conditions when escalation of therapy should be considered in DED.

PurposeTo investigate the levels of matrix metalloproteinases (MMPs) in aqueous humour of patients with retinal vein occlusion (RVO) and the relationship between intraocular MMP levels and retinal lesion and visual prognosis.Materials and methods52 RVO patients, including 23 with central retinal vein occlusion (CRVO) and 29 with branch retinal vein occlusion (BRVO) and 20 participants with senile cataract were enrolled in this study. Retinal lesions were examined by fundus colour photography, fluorescein fundus angiography and optical coherence tomographic angiography. Sixty microliters of aqueous humour were collected during intravitreal anti-Vascular Endothelial Growth Factor (VEGF) injection or cataract surgery. The aqueous levels of MMP-1, MMP-2, MMP-7, MMP-9 and MMP-10 were measured using the Luminex xMAP multiplex assay. The relationship between MMP levels and clinical presentations was analysed by Pearson correlation test.ResultsThe aqueous humour levels of MMP-1, MMP-2, MMP-7 and MMP-9, but not MMP10 in RVO patients were significantly higher than those in people with cataract after adjusting for age. Further analysis of RVO subgroups showed that the aqueous humour level of MMP2 in CRVO was significantly higher than that in BRVO. The aqueous humour levels of MMP-1 and MMP-2 were positively correlated with superficial capillary plexus vessel density (SVD), whereas the aqueous humour levels of MMP-1 and MMP-7 were negatively correlated with visual improvement following treatment. No correlation between aqueous humour levels of MMP and disease duration and central retinal thickness was observed.ConclusionsRVO eyes had significantly higher intraocular levels of MMP-1, MMP-2, MMP-7 and MMP-9 than cataract eyes and the level of MMP2 appears to be related to the area of occlusion. Intraocular levels of MMP may positively affect SVD and negatively impact visual function in RVO.

In a healthy eye, the aqueous humour (AH) flows via the ciliary body and trabecular meshwork into the collector channels, which carry it to the episcleral veins. In glaucoma, a heterogeneous group of eye disorders affecting approximately 60 million individuals worldwide, the juxtacanalicular meshwork offers greater resistance to the outflow of the AH, leading to an increase in outflow resistance that gradually results in elevated intraocular pressure (IOP). The present review comprehensively covers the morphology of Schlemm's canal (SC) and AH pathways. The path of the AH from the anterior chamber through the trabeculum into suprascleral and conjunctival veins via collector channels is described, and the role of SC in the development of glaucoma and outflow resistance is discussed. Finally, channelography is presented as a precise method of assessing the conventional drainage pathway and facilitating localization of an uncollapsed collector and aqueous veins. Attention is also given to the relationship between aqueous and episcleral veins and heartbeat. Possible directions of future research are proposed.

Fluoroquinilones play major role in prevention of infectious complications after cataract surgery. It is important to notice their speсtrum of antimicrobial асtivity as well their sаfety and bioаvаilаbility. In our research we aimed to study in vivo the mean time of minimal inhibitory concentration (MIC) of three different fluorquinolones in aqueous humour and role of preservative presence, as well as its concentration, in reaching MIC in aqueous humour. This was a randomized study, that included 90 patients treated with fluorquinolones by the same prescription 4 drops in 1 hour every 15 mins starting 60 minutes before planned phacoemulsification. We compared 1. Oftаquix™ (levofloxасin 0.5 %; Santen Oy, Finlаnd with 0,05 mg/ml preservative); 2. Signiсef® (levofloxасin 0.5 %; Sentiss Phаrmа Pvt. Ltd., Indiа — contains 0.1 mg/ml preservative) 3. Vigаmox® (moxifloxасin 0.5 %; Alсon Lаboratories, Inс., USА without preservative). We collected aqueous humour at the surgery beginning and measured the concentration of antimicrobial drug by method of highly effective liquid chromotogrаphy. The study showed that presence of preservative in different concentration may decrease the function of corneal epithelial barrier and change drug’s potential bioаvаilаbility. Prescription of fluorquionolones eyedrops in first few days after phacoemulsification allows to reduce the risk of endophtalmitis and avoid preservative-induced side effects in short period of use.

Purpose New instrument-based techniques for anterior chamber (AC) cell counting can offer automation and objectivity above clinician assessment. This review aims to identify such instruments and its correlation with clinician estimates. Methods Using standard systematic review methodology, we identified and tabulated the outcomes of studies reporting reliability and correlation between instrument-based measurements and clinician AC cell grading. Results From 3470 studies, 6 reported correlation between an instrument-based AC cell count to clinician grading. The two instruments were optical coherence tomography (OCT) and laser flare-cell photometry (LFCP). Correlation between clinician grading and LFCP was 0.66–0.87 and 0.06–0.97 between clinician grading and OCT. OCT volume scans demonstrated correlation between 0.75 and 0.78. Line scans in the middle AC demonstrated higher correlation (0.73–0.97) than in the inferior AC (0.06–0.56). Conclusion AC cell count by OCT and LFP can achieve high levels of correlation with clinician grading, whilst offering additional advantages of speed, automation, and objectivity.

OBJECTIVE: To investigate complement activation in aqueous humour of patients with early, intermediate and neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: Aqueous humour of 79 AMD patients (early, intermediate and neovascular) and 77 age-matched controls was prospectively collected. The levels of the complement protein 3 (C3), activation products complement factor 3a (C3a) and Ba, C3b/iC3b, complement factors B, H and I (CFB, CFH and CFI), and total protein concentration were measured. Data were modelled using covariate analysis to assess the impact of age and glaucoma status of patients and total protein concentration of samples on complement protein concentration across groups. RESULTS: C3a concentration was significantly increased in the aqueous humour of early (p = 0.016), intermediate (p = 0.003) and neovascular (p = 0.018) AMD patients, whilst C3 concentration was significantly increased in early AMD patients only (p = 0.019). Levels of CFB and CFH were significantly increased in the aqueous humour of neovascular AMD patients (p = 0.023 and p = 0.018, respectively). CONCLUSIONS: Our findings provide evidence for early local complement dysregulation in AMD patients, suggesting that complement pathway inhibition may be a clinically relevant intervention for early stages of AMD.

Intraocular pressure (IOP), the pressure within the eyeball, is a function mainly of the production and elimination of aqueous humour. Balanced IOP helps to maintain the eyeball contour, allowing proper refraction of light in the anterior segment of the eye. Increases in IOP can cause injury to the ocular structure, typically the optic nerve head and retinal ganglion cells. IOP increase, additionally, is a risk factor for glaucoma progression. However, it is not unusual that glaucoma worsens despite well-managed IOP; indeed, glaucoma can develop and progress even within the normal IOP range. IOP measured once during daytime office hours might not provide sufficient information for effective glaucoma management. In fact, IOP is not a fixed value but rather changes over time: it fluctuates with the intrinsic circadian rhythm and can also change in various lifestyle-related situations (eg, with body posture, during exercise, while holding breath and according to dietary habits). It is therefore worth exploring the various factors that can affect IOP and glaucoma risk. In this review, the various exogenous influences on IOP in the literature are investigated.

Purpose: to study eye hydrodynamics in children subjected to total intravenous anesthesia during ophthalmic operations. Materials and methods. 50 children (100 eyes) aged 15 days to 14 years were examined. 21 children showed impaired hydrodynamics while the remaining 29 had no hydrodynamic disorders. All patients received combined endotracheal anesthesia for ophthalmic operations.Results. The patients with undisturbed hydrodynamics showed a significant increase in true intraocular pressure (Po) (by 3.8 ± 0.12 mm Hg) after an injection of anesthesia with ketamine, due to a significant increase in aqueous humor production. Children with disturbed hydrodynamics, who received an antihypertensive ophthalmic drug (arutimol 0.25–0.5 %), after an injection of anesthesia with fentanyl, showed a significant Po decrease (by 3.9 ± 0.12 mm Hg) due to a significant increase of outflow facility rate (C) and a decrease in aqueous humour volume (F). The patients who received no antihypertensive therapy showed a significant decrease in Po (by 2.08 ± 0.7 mm Hg) due to a significant increase in C. In contrast, the decrease in F proved to be insignificant.Conclusion. For an objective assessment of tonographic parameters in children with impaired eye hydrodynamics who received antihypertensive therapy (arutimol 0.25–0.5 %) and anesthesized with fentanyl, we recommend that the Po indices be adjusted upwards by 3.9 ± 0.12 mm Hg, without arutimol by 2.08 ± 0.7 mm Hg, which will help in choosing the type and volume of antiglaucomatous operations. It is also necessary to take into account the increase in Po under the action of ketamine (by 3.8 ± 0.12 mm Hg) in children with undisturbed eye hydrodynamics to prevent possible intra- and postoperative complications.

Background/aimsPseudoexfoliation syndrome (PEX) is characterised by the production and accumulation of extracellular fibrillar material in the anterior segment of the eye. The pathogenesis of PEX is multifactorial with genetic factors and ageing as contributing factors. Previously, an increased concentration of beta-crystalline B2 (CRYBB2) was observed in the aqueous humour (AH) in eyes with PEX in a pooled material. Here, the protein content was examined on individual basis.MethodsDuring cataract surgery, AH was sampled from patients with and without PEX, 10 eyes in each group. The proteins were digested and labelled with isotopomeric dimethyl labels, separated with high-pressure liquid chromatography and analysed in an Orbitrap mass analyzer.ResultsThe concentration of complement factor 3, kininogen-1, antithrombin III and vitamin D-binding protein was increased in all eyes with PEX. Retinol-binding protein 3, glutathione peroxidase, calsyntenin-1 and carboxypeptidase E were decreased in eyes with PEX. Beta-crystalline B1 and CRYBB2 and gamma-crystalline D were up to eightfold upregulated in 4 of 10 in eyes with PEX.Conclusion The results indicate that oxidative stress and inflammation are contributing factors in the formation of PEX. Knowledge about the proteome in PEX is relevant for understanding this condition.

BackgroundToxoplasma gondiiis the most common infectious cause of posterior uveitis worldwide. Two multicopy targets (B1 and Rep529) are commonly used inT. gondiiPCR assays, but studies evaluating these targets in ocular fluid samples are limited. Herein, we determine the analytical characteristics of a single-reaction, internally controlled, dual-target, real-timeT. gondiiPCR and evaluate the clinical performance of this assay in intraocular fluid samples obtained at a reference ophthalmologic centre in the USA.MethodsLower limits of detection for the B1 and Rep529 components of the dual-target assay were determined using serial dilutions of culturedT. gondiistrain Z185. The dual-target assay was then used to test 148 archived intraocular samples (132 vitreous,16 aqueous humour) collected at the Francis I. Proctor Foundation between January 2010 and December 2015 for testing by a nested, conventional PCR targeting the B1 gene.ResultsThe 95% lower limits of detection for the dual-target assay was determined to be 1.05 tachyzoites/mL for B1 and 0.83 tachyzoites/mL for Rep529. Using archived clinical intraocular specimens, the dual-target assay demonstrated 97.2% positive per cent agreement (n=35/36; 95% CI 83.7% to 99.9%) and 99.1% negative per cent agreement (n=111/112; 95% CI 94.4% to 100%) compared with the nested, conventional B1 PCR.ConclusionThis single-reaction, internally controlled, dual-target (B1, Rep529) real-time PCR for the detection ofT. gondiiDNA in intraocular specimens demonstrated excellent agreement with nested, conventional, B1 PCR. The dual-target design may ensureT. gondiidetection when variation is present in one of two target regions.

Latanoprostene bunod (LBN) ophthalmic solution 0.024% is a novel, once-daily, nitric oxide-donating prostaglandin analogue for the lowering of intraocular pressure (IOP) in patients with open-angle glaucoma and ocular hypertension. The IOP-lowering actions of LBN are mediated by dual mechanisms of the molecule for increasing aqueous humour outflow. The prostaglandin analogue moiety (latanoprost acid) increases uveoscleral outflow, whereas nitric oxide, released by the nitric oxide-donating moiety (butanediol mononitrate), increases outflow through the trabecular meshwork and the Schlemm's canal. The clinical efficacy and safety of LBN 0.024% in patients with open-angle glaucoma or ocular hypertension were established in two similarly designed, double-masked, pivotal phase 3 studies, APOLLO and LUNAR, the pooled three-month efficacy phase of which demonstrated significantly greater IOP-lowering of once-daily LBN 0.024% over twice-daily timolol 0.5% at all time points. Additional support for the IOP-lowering effects of LBN 0.024% was provided by two phase 2 studies in patients with open-angle glaucoma or ocular hypertension (a dose ranging study versus latanoprost and a 24-hour IOP crossover study versus timolol) and a phase 1 study of healthy volunteers with IOP in the normal range. In addition, long-term efficacy and safety were demonstrated in the open-label safety-extension phases of the phase 3 pivotal studies and a phase 3 52-week open-label study of patients with open-angle glaucoma (including normal-tension glaucoma) or ocular hypertension. In conclusion, LBN 0.024% has demonstrated both short-term and long-term IOP-lowering efficacy in patients with open-angle glaucoma or ocular hypertension, including in healthy volunteers and patients with IOP in the normal range, without apparent clinically-limiting safety or tolerability concerns.

Carbonic anhydrase inhibitors (CAIs) have been used for many decades in the treatment of glaucoma. Systemic CAIs were an early treatment option to lower intraocular pressure by reducing aqueous humour production; however, frequent side effects including polyuria and paresthesia contributed to the eventual development of topical CAIs. As topical drug development evolved over time, prostaglandin analogues and beta-blockers have become the gold standard of glaucoma therapies. Although prescribed less often than other classes of topical glaucoma therapies, topical CAIs continue to be used in combination therapies with beta-blockers and alpha agonists. Topical CAIs have also been demonstrated to alter biomarkers of ocular haemodynamics, which have relevance in glaucoma. The purpose of this review is to review and summarise the current state of topical CAI prescribing trends, known efficacy and suggested mechanisms and potential influence on ocular haemodynamics for the future of glaucoma management.

PURPOSE In eyes with diabetic macular oedema (DME), aqueous humour (AH) cytokine levels before and after anti-vascular endothelial growth factor (VEGF) treatment were compared and correlated with optical coherence tomography structural parameters. METHODS This prospective study included 56 control patients with cataracts and 83 patients with DME manifesting as diffuse retinal thickening (DRT), cystoid macular oedema and serous retinal detachment (SRD). AH samples were obtained before intravitreal injection of anti-VEGF or cataract surgery. VEGF, interleukin (IL)-6, IL-8, IL-10, interferon-inducible protein 10 (IP-10) and monocyte chemotactic protein 1 (MCP-1) levels were measured by multiplex bead assay. AH cytokine levels, central macular thickness (CMT), number of hyper-reflective foci (HF), continuity of external limiting membrane and ellipsoid zone (EZ) and best-corrected visual acuity were evaluated. RESULTS In SRD, IL-6 and MCP-1 levels and HF were increased (all p

Glaucoma is the most common form of irreversible blindness in the world. Lowering intraocular pressure (IOP) remains the only clinically established method of treatment to slow the progression of glaucoma. Primary open angle glaucoma is a disease of the optic nerve head and often is associated with changes to the trabecular meshwork that cause a reduction to aqueous humour outflow and an increase in intraocular pressure. Until recently, topical IOP lowering medication has been limited to the mechanisms of action of decreasing aqueous production and/or redirecting outflow to the unconventional uveoscleral outflow pathway. Both of these mechanisms neglect to treat or act on tissue that becomes altered from glaucoma. Latanoprostene-bunod 0.024%, a nitric-oxide donating prostanoid, netarsudil 0.02%, a potent Rho-associated protein kinase (ROCK) inhibitor and norepinephrine transporter inhibitor, and a once daily dosed fixed combination medication with netarsudil 0.02% and latanoprost 0.005% have recently come on the market. This paper will discuss and review the limitations to traditional IOP lowering glaucoma medications as well as the mechanism of actions and clinical efficacy of the new glaucoma medications. It will also discuss how the new class of glaucoma medications might help to overcome some known limitations in treatment and barriers to patient adherence.