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Background: Accurate inflammatory mechanisms in chronic ocular surface diseases (OSDs) cannot routinely be assessed. New techniques for investigating ocular surface inflammatory pathways are of major importance. Objective: To investigate the expressions of CCR4 and CCR5, known to be related to the TH2 and TH1 systems, respectively, and HLA-DR in conjunctival impression cytology specimens from patients with chronic OSDs. Methods: In this case-controlled study, impression cytology specimens were taken in a series of patients with vernal keratoconjunctivitis (n=21), giant papillary conjunctivitis (n=6), or keratoconjunctivitis sicca (KCS; n=17), or receiving topical antiglaucoma treatments (n=31), and from 20 normal subjects. Conjunctival cells were incubated with mAbs to CCR4, CCR5, CD45, and HLA-DR to quantify conjunctival inflammation in a masked manner using flow cytometry. Results: HLA-DR was higher in the glaucoma and KCS groups than in allergic and normal eyes. CCR4 was overexpressed in allergy and glaucoma, whereas CCR5 was higher in the KCS and glaucomatous groups. CD45 was expressed by only few cells in all groups, with almost no significant differences. CCR4 expression was negatively correlated with CCR5 and HLA-DR, whereas CCR5 was positively correlated with HLA-DR. Conclusion: This study confirms the overexpression of chemokine receptors by the conjunctival epithelium in OSDs. CCR4 and CCR5 expression may vary according to the immune pathway involved. Accurate mechanisms in ocular surface inflammatory reactions—that is, those related to the TH1 or TH2 systems—could be differentiated by CCR4/CCR5 profiles. Our results also suggest that long-term use of topical treatments may stimulate both systems. [Copyright &y& Elsevier]

To compare the efficacy and the safety of submacular hemorrhage (SMH) management using either surgical pars plana vitrectomy (PPV) or pneumatic displacement (PD) with tissue plasminogen activator (tPA) and vascular endothelial growth factor (VEGF) inhibitor added to each arm. Randomized, open-label, multicenter superiority study. Ninety patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older with recent SMH (≤ 14 days) of more than 2 optic disc areas and predominantly overlying the retinal pigment epithelium. Patients were assigned randomly to surgery (PPV, subretinal tPA [maximum, 0.5 ml/50 μg], and 20% sulfur hexafluoride [SF 6 ] tamponade) or PD (0.05 ml intravitreal tPA [50 μg] and 0.3 ml intravitreal pure SF 6). Both groups were asked to maintain a head upright position with the face forward at 45° for 3 days after intervention and received 0.5 mg intravitreal ranibizumab at the end of the intervention, at months 1 and 2, as the loading phase, and then on a pro re nata regimen during a 6-month follow-up. The primary efficacy endpoint was mean best-corrected visual acuity (VA) change at month 3. The secondary endpoints were mean VA change at month 6, 25-item National Eye Institute Visual Function Questionnaire composite score value at months 3 and 6, number of anti-VEGF injections, and complications during the 6-month follow-up. Of the 90 patients randomized, 78 patients (86.7%) completed the 3-month efficacy endpoint visit. The mean VA change from baseline to month 3 in the surgery group (+16.8 letters [95% confidence interval (CI), 8.7–24.9 letters]) was not significantly superior to that in the PD group (+16.4 letters [95% CI, 7.1–25.7 letters]; adjusted difference β, 1.9 [–11.0; 14.9]; P = 0.767). Both groups achieved similar secondary outcomes at month 6. No unexpected ocular safety concerns were observed in either group. Surgery did not yield superior visual gain nor additional benefit for SMH secondary to nAMD compared with PD at 3 months, with intravitreal anti-VEGF added to each arm. Both treatment strategies lead to a clinical improvement of VA without safety concerns for SMH over 6 months. Both design and results of the trial cannot be used to establish equivalence between treatments. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

To investigate the association of commonly used systemic medications with glaucoma and intraocular pressure (IOP) in the European population. Meta-analysis of 11 population-based cohort studies of the European Eye Epidemiology Consortium. The glaucoma analyses included 143 240 participants and the IOP analyses included 47 177 participants. We examined associations of 4 categories of systemic medications—antihypertensive medications (β-blockers, diuretics, calcium channel blockers [CCBs], α-agonists, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers), lipid-lowering medications, antidepressants, and antidiabetic medications—with glaucoma prevalence and IOP. Glaucoma ascertainment and IOP measurement method were according to individual study protocols. Results of multivariable regression analyses of each study were pooled using random effects meta-analyses. Associations with antidiabetic medications were examined in participants with diabetes only. Glaucoma prevalence and IOP. In the meta-analyses of our maximally adjusted multivariable models, use of CCBs was associated with a higher prevalence of glaucoma (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.08 to 1.39). This association was stronger for monotherapy of CCBs with direct cardiac effects (OR, 1.96; 95% CI, 1.23 to 3.12). No other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were associated with glaucoma. Use of systemic β-blockers was associated with a lower IOP (β coefficient, −0.33 mmHg; 95% CI, −0.57 to −0.08 mmHg). Monotherapy of both selective systemic β-blockers (β coefficient, −0.45 mmHg; 95% CI −0.74 to −0.16 mmHg) and nonselective systemic β-blockers (β coefficient, −0.54 mmHg; 95% CI, −0.94 to −0.15 mmHg) was associated with lower IOP. A suggestive association was found between use of high-ceiling diuretics and lower IOP (β coefficient, −0.30 mmHg; 95% CI, −0.47 to −0.14 mmHg) but not when used as monotherapy. No other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were associated with IOP. We identified a potentially harmful association between use of CCBs and glaucoma prevalence. Additionally, we observed and quantified the association of lower IOP with systemic β-blocker use. Both findings potentially are important, given that patients with glaucoma frequently use systemic antihypertensive medications. Determining causality of the CCB association should be a research priority. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

Randomised clinical trials (RCTs) are generally considered the gold-standard for providing scientific evidence for treatments' effectiveness and safety but their findings may not always be generalisable to the broader population treated in routine clinical practice. RCTs include highly selected patient populations that fit specific inclusion and exclusion criteria. Although they may have a lower level of certainty than RCTs on the evidence hierarchy, real-world data (RWD), such as observational studies, registries and databases, provide real-world evidence (RWE) that can complement RCTs. For example, RWE may help satisfy requirements for a new indication of an already approved drug and help us better understand long-term treatment effectiveness, safety and patterns of use in clinical practice. Many countries have set up registries, observational studies and databases containing information on patients with retinal diseases, such as diabetic macular oedema (DMO). These DMO RWD have produced significant clinical evidence in the past decade that has changed the management of DMO. RWD and medico-administrative databases are a useful resource to identify low frequency safety signals. They often have long-term follow-up with a large number of patients and minimal exclusion criteria. We will discuss improvements in healthcare information exchange technologies, such as blockchain technology and FHIR (Fast Healthcare Interoperability Resources), which will connect and extend databases already available. These registries can be linked with existing or emerging retinal imaging modalities using artificial intelligence to aid diagnosis, treatment decisions and provide prognostic information. The results of RCTs and RWE are combined to provide evidence-based guidelines. • RWE has produced valuable insights into the optimal management of DMO. • Combined with RCT data, RWE provide effective evidence-based DMO guidelines. • RWD helps to identify low frequency safety signals notably for novel approved drugs. • RWD will gain from new powerful technologies like AI, big-data or software linkage. [ABSTRACT FROM AUTHOR]

Abstract: N-6 and n-3 polyunsaturated fatty acids (PUFAs) have been shown to prevent tissue release of inflammatory molecules. We have shown that a combination of n-6 and n-3 PUFAs is more efficient than single supplementations on the long-term consequences of intraocular pressure elevation. We hypothesized that such an association is also more effective during early retinal stress by modifying retinal proinflammatory prostaglandin and cytokine productions. Rats were supplemented for 3 months with n-6 PUFAs, n-3 PUFAs, or both n-6 and n-3 PUFAs. After 3 months, a surgical elevation of intraocular pressure was induced. Retinal morphometry and glial cell activation were evaluated 24 hours after laser treatment. The retinal levels of prostaglandin E1 (PGE1) and prostaglandin E2 (PGE2) and the messenger RNA levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α were measured. Retinal glial cell activation after laser treatment was partly prevented by dietary n-6, n-3, and n-6 and n-3 PUFAs. Retinal PGE1 was unaffected by the laser treatment or by the diet. Dietary n-6 and/or n-3 PUFAs prevented the increase in PGE2 levels observed in laser-treated retinas without affecting the induction of interleukin-1β, interleukin-6, and tumor necrosis factor-α messenger RNAs. This study shows that not only a combination of n-6 and n-3 PUFAs but also single supplementations can preserve the retina from early glial cell activation and PGE2 release. The protective effect is not mediated by changes in cytokine expression but may be related to modifications in retinal prostaglandin metabolism. [Copyright &y& Elsevier]

Purpose: To assess the functional and anatomic outcomes of cataract and idiopathic epiretinal macular membrane extraction in combined and consecutive surgeries. Design: Multicenter, retrospective, comparative case series. Methods: One hundred seventy-four patients (174 eyes) with an epiretinal macular membrane (ERM) and cataract were operated on in 1 or 2 sessions in 2 academic centers, Dijon University Hospital and Nancy University Hospital. Combined surgery (n = 109) and consecutive surgery (n = 65) were performed between 2005 and 2006. All patients underwent ERM and internal limiting membrane removal. Cataract extraction was performed with phacoemulsification followed by a posterior chamber intraocular lens implantation. The main outcome measures were near and far visual acuity and central macular thickness evaluated with optical coherence tomography. Results: After a 12-month follow-up, the postoperative best-corrected visual acuities significantly improved in both the combined and the consecutive surgery groups (near and far vision in both groups, P < .0001). Similarly, the postoperative macular thickness significantly decreased in both groups (P < .0001). We noted no statistical differences between the visual acuity improvement in both groups (near vision, P= .54; far vision, P = .38). However, visual acuity recovery was quicker in the combined surgery group. Conclusions: Combined and consecutive surgeries are effective procedures to treat idiopathic ERM. The functional and anatomic results are equivalent in both procedures. [Copyright &y& Elsevier]