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To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody.YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6·0 mg every 8 weeks, faricimab 6·0 mg per personalised treatment interval (PTI), or aflibercept 2·0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (YOSEMITE NCT03622580 and RHINE NCT03622593).3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10·7 ETDRS letters [97·52% CI 9·4 to 12·0] vs 10·9 ETDRS letters [9·6 to 12·2], difference -0·2 ETDRS letters [-2·0 to 1·6]; RHINE 11·8 ETDRS letters [10·6 to 13·0] vs 10·3 ETDRS letters [9·1 to 11·4] letters, difference 1·5 ETDRS letters [-0·1 to 3·2]) and faricimab PTI (YOSEMITE 11·6 ETDRS letters [10·3 to 12·9], difference 0·7 ETDRS letters [-1·1 to 2·5]; RHINE 10·8 ETDRS letters [9·6 to 11·9], difference 0·5 ETDRS letters [-1·1 to 2·1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31%], RHINE n=137 [43%]), faricimab PTI (n=106 [34%], n=119 [37%]), and aflibercept every 8 weeks (n=102 [33%], n=113 [36%]).Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema.F Hoffmann-La Roche.

Faricimab is a bispecific antibody that acts through dual inhibition of both angiopoietin-2 and vascular endothelial growth factor A. We report primary results of two phase 3 trials evaluating intravitreal faricimab with extension up to every 16 weeks for neovascular age-related macular degeneration (nAMD).TENAYA and LUCERNE were randomised, double-masked, non-inferiority trials across 271 sites worldwide. Treatment-naive patients with nAMD aged 50 years or older were randomly assigned (1:1) to intravitreal faricimab 6·0 mg up to every 16 weeks, based on protocol-defined disease activity assessments at weeks 20 and 24, or aflibercept 2·0 mg every 8 weeks. Randomisation was performed through an interactive voice or web-based response system using a stratified permuted block randomisation method. Patients, investigators, those assessing outcomes, and the funder were masked to group assignments. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48 (prespecified non-inferiority margin of four letters), in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (TENAYA NCT03823287 and LUCERNE NCT03823300).Across the two trials, 1329 patients were randomly assigned between Feb 19 and Nov 19, 2019 (TENAYA n=334 faricimab and n=337 aflibercept), and between March 11 and Nov 1, 2019 (LUCERNE n=331 faricimab and n=327 aflibercept). BCVA change from baseline with faricimab was non-inferior to aflibercept in both TENAYA (adjusted mean change 5·8 letters [95% CI 4·6 to 7·1] and 5·1 letters [3·9 to 6·4]; treatment difference 0·7 letters [-1·1 to 2·5]) and LUCERNE (6·6 letters [5·3 to 7·8] and 6·6 letters [5·3 to 7·8]; treatment difference 0·0 letters [-1·7 to 1·8]). Rates of ocular adverse events were comparable between faricimab and aflibercept (TENAYA n=121 [36·3%] vs n=128 [38·1%], and LUCERNE n=133 [40·2%] vs n=118 [36·2%]).Visual benefits with faricimab given at up to 16-week intervals demonstrates its potential to meaningfully extend the time between treatments with sustained efficacy, thereby reducing treatment burden in patients with nAMD.F Hoffmann-La Roche.

Objective To evaluate the effectiveness, treatment patterns and long-term safety of ranibizumab 0.5 mg in treatment-naïve patients with central retinal vein occlusion (CRVO) in a real-world setting. Methods LUMINOUS, a 5-year, global, prospective, multicentre, multi-indication, observational, open-label study, recruited treatment naïve or prior treated patients who were treated as per the local ranibizumab label. Here, we report the mean change in visual acuity (VA; Early Treatment Diabetic Retinopathy Study [ETDRS] letters), treatment exposure over year (Y) 1 and 5-year safety in treatment-naïve CRVO patients. Results At baseline, the mean age of treatment-naïve CRVO patients (n = 327) was 68.9 years, with a mean (Standard deviation [SD]) VA of 40.6 (23.9) letters. At Y1, patients (n = 144) had a mean (SD) VA gain from baseline of 10.8 (19.66) letters, with a mean (SD) of 5.4 (2.65) ranibizumab injections. Patients demonstrated mean (SD) VA gains of 2.7 (19.35), 11.6 (20.56), 13.9 (18.08), 11.1 (18.46) and 8.2 (24.86) letters with 1, 2–3, 4–5, 6–8 and >8 ranibizumab injections, respectively. Mean (SD) VA gains at Y1 in patients receiving loading (67.4%) and no loading dose (32.6%) was 11.9 (20.42) and 8.4 (17.99) letters, respectively. Over five years, the incidence of ocular/non-ocular adverse events (AEs) and serious AEs was 11.3%/8.6% and 1.2%/6.7%, respectively. Conclusions These results demonstrate the effectiveness of ranibizumab in treatment-naïve CRVO patients at Y1 with clinically meaningful VA gains and no new safety findings over five years. These findings may help inform routine practice and enable better clinical management to achieve optimal visual outcomes.

Background Hemodynamic changes have been observed in patients with Graves’ disease. The aim of our study was to evaluate choroidal vascular change using the choroidal vascularity index (CVI) in patients with thyroid-associated ophthalmopathy (TAO). Methods In this cross-sectional observational study, 40 patients affected by TAO were recruited. Forty healthy individuals, matched for age and sex, served as controls. Foveal enhanced-depth imaging optical coherence tomography scans were obtained from all participants. Images were binarized using the ImageJ software and luminal area (LA) and total choroidal area (TCA) were measured. CVI was calculated as the proportion of LA to TCA. The relation between CVI or subfoveal choroidal thickness (SFCT) and clinical activity score, exophthalmometric value, diplopia status, gender, and age was evaluated. Results CVI was significantly higher in patients with TAO (P = 0.004). No significant difference was observed in SFCT (P = 0.200) and TCA (P = 0.153) comparing TAO patients and healthy controls. LA was significantly higher in TAO group (P = 0.045). On multiple regression analysis, CVI was associated with TCA (P = 0.043). No association was found between SFCT or CVI and TCA, clinical activity score, exophthalmometric value, Inami value, diplopia status, gender or age (P > 0.05). Conclusions This is the first study that has demonstrated an increase in CVI in eyes with TAO compared with healthy controls and has assessed its association with clinical features.

Purpose To estimate the frequency of epiretinal membrane (ERM) in eyes with primary open-angle glaucoma (POAG) treated with Ex-Press shunt implant. Secondarily, we aimed to assess the role of concomitant cataract surgery and the impact of the ERM on central foveal thickness and macular volume. Methods In this prospective, consecutive, case-control study, we enrolled 54 patients affected by PAOG and scheduled for Ex-Press device implant with or without contemporary phacoemulsification. Contralateral eyes affected by POAG and receiving anti-glaucomatous eyedrops constituted the control group. Complete ophthalmologic evaluation and spectral-domain optical coherence tomography (OCT) were performed before and 1, 3 and 6 months after surgery. Results Twenty-six eyes received the Ex-Press implant alone, and 28 eyes underwent the combined procedure. Six months postoperatively, we observed 18 (33%) cases of ERM: 15 (28%) of cellophane macular reflex (CMR) and 3 (6%) of pre-macular fibrosis (PMF). In the control group, 9 (17%) eyes developed an ERM: 8 (15%) were CMR, and 1 (2%) was PMF. The frequency of ERM statistically differs between treated and contralateral eyes (P = 0.032, χ2 test). The ERM frequency did not statically differ between eyes subjected to simple or combined surgery (P = 0.846, χ2 test). Mean central foveal thickness and mean macular volume did not significantly differ between groups. Conclusion The Ex-Press glaucoma shunt may increase the risk of ERM onset regardless of the concomitant cataract surgery; however, most cases were cellophane macular reflex with limited functional and anatomical impact.

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

We report anesthetic management in a patient with Brugada syndrome, an inherited syndrome characterized by normal QT interval, typical ST-segment–elevation in the right precordial leads, and increased risk of sudden cardiac death in the absence of myocardial ischemia or structural heart disease. A 69-year-old man scheduled for glaucoma filtering surgery underwent local peribulbar anesthesia using 5 mL of lidocaine 20 mg/mL solution that was slowly injected into two different sites approximately 10 min prior to the surgical procedure. The surgery proceeded uneventful and data of patient’s blood pressure, heart rate, oxygen saturation were collected. Continuous electrocardiography monitoring before, during, and up to 6 h after surgery did not reveal any arrhythmia or tachycardia. A certain number of drugs should be avoided in patients with Brugada syndrome because of their potential risk to trigger an arrhythmia. Among them there are some anesthetics and in particular those that are sodium channel blockers. Ropivacaine and bupivacaine, commonly used for peribulbar block, have been associated with onset of severe arrhythmias. Contrarily, the use of class IB drugs mexiletine and lidocaine is generally considered safe. Local anesthetic agent should be carefully chosen, and anesthesia should be obtained using the minimal necessary drug dose.

The extent to which mononuclear cells and TSH-receptor autoantibodies (TRAb) contribute to Graves’ orbitopathy (GO) is not completely defined. Here we investigated the relationship between the immunohistochemical phenotype of orbital infiltrating cells and GO features in a large number of patients. We conducted an observational cohort study in 76 consecutive patients with GO (16 men and 60 women) who underwent orbital decompression over a period of 18 consecutive months. An ophthalmological evaluation was performed in all patients, as well as immunohistochemistry for CD3, CD4, CD8, CD56 (T-cell markers), CD25 (T and B-cell marker), CD20, CD19 (B-cell markers), and CD138 (plasmacell marker) in specimens collected at decompressive surgery. Having established cutoff values for each marker, cell infiltrates were found in 60 patients (78.9%; CD3: 39.4%, CD4 55.2%, CD8 50%, CD56: 0%, CD25: 28.9%, CD20: 51.3%, CD19: 25%, CD138: 26.3%). Eleven (14.4%) stained exclusively for CD138 (plasmacells). Patients with CD4-positive mononuclear cells had a significantly greater GO clinical activity score (CAS) (mean difference 1.07, 95% CI − 0.33 to − 1.82, P = 0.004 by univariate, P = 0.05 by multivariate analysis). CAS as well as the remaining GO features were not affected significantly by the mononuclear cell subpopulations in multivariate analyses. Mononuclear cell infiltrates are present in the majority of GO patients, with a small percentage represented exclusively by plasmacells. CD4 cells exert a major role on GO activity. These findings may represent a further advancement in the comprehension of GO pathogenesis.

Background/objectives: To compare the number of eye surgical procedures performed in Italy in the 2 months following the beginning of lockdown (study period) because of COVID-19 epidemic with those performed in the two earlier months of the same year (intra-year control) and in the period of 2019 corresponding to the lockdown (inter-year control). Methods: Retrospective analysis of surgical procedures carried out at 39 Academic hospitals. A distinction was made between elective and urgent procedures. Intravitreal injections were also considered. Percentages for all surgical procedures and incidence rate ratios (IRR) for rhegmatogenous retinal detachment (RRD) events were calculated. A p value Results: A total of 20,886 versus 55,259 and 56,640 patients underwent surgery during the lockdown versus intra-and inter-year control periods, respectively. During the lockdown, only 70% of patients for whom an operation/intravitreal injection was recommended, finally underwent surgery; the remaining patients did not attend because afraid of getting infected at the hospital (23%), taking public transportation (6.5%), or unavailable swabs (0.5%). Elective surgeries were reduced by 96.2% and 96.4%, urgent surgeries by 49.7% and 50.2%, and intravitreal injections by 48.5% and 48.6% in the lockdown period in comparison to intra-year and inter-year control periods, respectively. IRRs for RRDs during lockdown dropped significantly in comparison with intra- and inter-year control periods (CI: 0.65–0.80 and 0.61–0.75, respectively, p Conclusion: This study provides a quantitative analysis of the reduction of eye surgical procedures performed in Italy because of the COVID-19 epidemic.

Purpose: To examine retinal displacement after vitrectomy with internal limiting membrane peeling for epiretinal membrane treatment, and to determine the correlation between the extent of displacement and the ganglion cell layer thickness changes. Methods: Thirty-nine consecutive patients were evaluated. Optical coherence tomography was performed preoperatively, and 2 and 6 months postoperatively. The distance between the fovea, the vessel intersection in the superior nasal, superior temporal, inferior nasal, and inferior temporal macular regions, and the optic disk were measured. Ganglion cell layer thickness was recorded. Results: The distance from the optic disk to the fovea and the superior nasal and inferior nasal vessel intersections significantly reduced at 2 and 6 months. Ganglion cell layer thickness significantly decreased in all the subfields (except nasal) at 6 months. A significant negative correlation was found between the change in the ganglion cell layer thickness and the movement of the fovea toward the optic disk. The ganglion cell layer thickness changes significantly correlated with retinal displacement. Conclusion: Retinal displacement toward the optic disk was detected after vitrectomy with internal limiting membrane peeling in eyes with epiretinal membrane. Ganglion cell layer thickness significantly reduced in all the subfields (except nasal). The extent of the displacement and the ganglion cell layer thickness changes showed significant negative correlation.

Purpose To evaluate the 10-year follow-up efficacy and safety of gold micro shunt (GMS) in patients with refractory glaucoma, and the potential risk factors for failure. Methods Retrospective data analyses based on medical records from 55 patients who underwent GMS implant for refractory glaucoma between March 2007 and April 2008. The primary outcome measure was the cumulative probability of success defined as intraocular pressure (IOP) below 21 mmHg together with a 33% lowering of the baseline IOP with (qualified) or without (complete) topical medications, no reoperation for glaucoma or loss of light perception. Results Mean IOP 10 years after the GMS implantation was 21.6 ± 5.1 mmHg with 2.7 ± 0.7 drugs. Qualified success was achieved in 8/55 patients (14.5%) with a mean of 2.9 ± 0.8 drugs at 5 years and in 2/55 patients (3.6%) with a mean of 2.7 ± 1.0 drugs at 10 years. None of the patients reached complete success at five years from surgery. The cumulative probability of complete success was 14%, 9% and 0% at 1, 2 and 5 years, respectively, and 72%, 67%, 36% and 3.6% at 1, 2, 5 and 10 years, respectively, for qualified success criterion. Baseline IOP for complete success, number of baseline medication for qualified success and age at the time of GMS implantation for both criteria were risk factors significantly associated with failure. Conclusion A very low long-term survival rate of GMS in refractory glaucoma was found. Most patients did not reach the IOP success criteria of the study, even with the re-introduction of medications, leading to the need for further surgical procedures.

Summary Background A protective action of statins on development of Graves' orbitopathy suggests that statins might be used for treatment of the disease. We aimed to assess the efficacy of the addition of a statin, atorvastatin, to intravenous glucocorticoids (ivGCs) on Graves' orbitopathy outcomes in patients with hypercholesterolaemia. Methods We did a randomised, open-label, phase 2, adaptive, clinical trial at a single, tertiary, referral hospital in Pisa, Italy. Patients with moderate-to-severe, active Graves' orbitopathy, with a low-density lipoprotein cholesterol concentration between 2·97 and 4·88 mmol/L were eligible for inclusion. Patients were randomly assigned (1:1) in 11 blocks of eight, using a computer-based system, to the ST group or the NST group. The ST group received ivGCs (methylprednisolone 500 mg once a week for 6 weeks followed by 250 mg once a week for an additional six weeks) for 12 weeks and oral atorvastatin (20 mg once a day) for 24 weeks. The NST group only received the ivGC regimen. Patients were unmasked to group allocation; however, the ophthalmological investigator was masked to randomisation. The primary endpoint was the Graves' orbitopathy outcome (composite evaluation of exophthalmos, clinical activity score, eyelid aperture, and diplopia) at 24 weeks in the modified intention-to-treat (ITT) population (patients who attended the week 12 visit). Patients were considered responders when at least two of the following criteria were fulfilled in the most affected eye, without worsening in any of the same measures in both eyes: (1) reduction in exophthalmos of 2 mm or more, with no increase by 2 mm or more in the other eye; (2) reduction of clinical activity score by two or more points; (3) reduction in eyelid aperture by 2 mm or more, with no increase by 2 mm or more in the other eye; and (4) disappearance or improvement (change from constant to inconstant, intermittent, or absent, or from inconstant to intermittent or absent) of diplopia, and (5) improvement in visual acuity by 0·2 decimals or more. The trial is registered with EUDRACT, 2018-001317-33, and ClinicalTrials.gov , NCT03110848 . Findings Between June 1, 2020, and Nov 30, 2020, 119 patients were screened for inclusion, of whom 88 (74%) patients were enrolled and randomly assigned to one of the two treatment groups (44 [50%] to the ST group and 44 [50%] to the NST group). Eight (9%) patients did not attend the 12 week visit; 80 (91%) patients (18 [23%] men and 62 [78%] women) were included in the modified ITT population (41 [51%] in the ST group and 39 [49%] in the NST group]. The proportion of Graves' orbitopathy composite evaluation responders at 24 weeks was higher in the ST group (21 [51%] of 41 patients) than the NST group (11 [28%] of 39 patients; attributable risk 0·23 [95% CI 0·02–0·44]; p=0·042). 26 adverse events occurred in 21 (24%) of 88 patients in the safety population. One (2%) of 44 patients in each group required treatment discontinuation, with no serious adverse events and no difference between groups. Interpretation Addition of oral atorvastatin to an ivGC regimen improved Graves' orbitopathy outcomes in patients with moderate-to-severe, active eye disease who were hypercholesterolaemic. Future phase 3 studies, which could potentially recruit patients regardless of low-density lipoprotein cholesterol concentration, are required to confirm this association. Funding Associazione Allievi Endocrinologia Pisana.

Thyrocytes secrete CXC chemokines, particularly (C-X-C motif) ligand (CXCL)8 and CXCL10; its physiopathological significance remains unclear. This study investigates the modulation of the secretion of CXCL8 vs. CXCL10, in human primary cells cultures of thyroid follicular cells (TFC) in Graves' disease (GD), and fibroblasts (OF) or preadipocytes (OP) from Graves' ophthalmopathy (GO).Cells were initially incubated with different concentrations of tumor necrosis factor (TNF)α (1, 5, 10 ng/mL). Then, CXCL8 and CXCL10 were measured in the supernatants of TFC, OF or OP cells basally and after 24 h of treatment with interferon (IFN)γ (1000 IU/mL) and/or TNFα (10 ng/mL), in presence/absence of the peroxisome proliferator activated receptor (PPAR)γ agonist pioglitazone (0, 0.1, 1, 5, 10, 20 μM), or the PPARα agonist fenofibrate (5, 10, 50, 100 μM).CXCL8, not CXCL10, was detected in basal conditions in TFC, OF and OP. CXCL8 secretion increased dose-dependently with increasing concentrations of TNFα. CXCL10 secretion was significantly stimulated by IFNγ (P 0.01) and not by TNFα, whereas CXCL8 was induced by TNFα (P 0.01), and inhibited by IFNγ (P 0.01) in TFC, OF and OP. Combining TNFα and IFNγ, the IFNγ-induced CXCL10 secretion was synergistically increased (P 0.01) while the TNFα-induced CXCL8 secretion (P 0.01) was reversed in all cell types. Pioglitazone had no significant effect on the secretion of CXCL8 stimulated by TNFα, while inhibited CXCL10. Fenofibrate, in presence of IFNγ plus TNFα, dose-dependently inhibited both CXCL10 and CXCL8 release.We first show that TFC, OF, and OP secrete CXCL8 and CXCL10 differentially, sustained by specific proinflammatory cytokines or their combination. This could reflect a different role of the two chemokines in the course of the disease, as CXCL10 could be associated with the initial phase of the disease when IFNγ is preponderant, while CXCL8 could be associated with a later chronic phase of the disease, when TNFα prevails.

Central serous chorioretinopathy is one of the most frequent causes of vision reduction among middle-aged men. This disease usually has a self-limiting course, but sometimes it lasts more than 4-6 months or a second episode follows a complete resolution of the first one. Nevertheless, to date no consensus exists about the duration threshold and therapy protocols for these non-resolving central serous chorioretinopathy. Treatment as half-dose and half-fluence photodynamic therapy, subthreshold micropulse laser treatment, mineralocorticoid receptor antagonists, intravitreal anti-angiogenic drugs, transpupillary thermal therapy, anti-androgenic drugs, methotrexate, Rifampicin and melatonin are described in this review. Complications are very uncommon but end-point results like central macular thickness reduction and best-corrected visual acuity improvement are difficult to compare among different therapeutic modalities due to different duration of follow-up and lack of homogeneity in patient recruitment. The aim of this review is focusing on treatment modalities for these chronic forms with comprehensive recent management updates according to latest clinical trial results.摘要: 中心性浆液性脉络膜视网膜病变是导致中年男性视力下降最常见的原因之一。这种疾病通常具有自限性, 但有时它会持续4-6个月以上, 或在第一次治愈后复发。然而, 迄今为止, 人们对于这种难治性中心性浆液性脉络膜视网膜病变的时间阈值和治疗方案尚未达成共识。本文综述了半剂量、半效应光动力疗法、阈下微脉冲激光光凝治疗、盐皮质激素受体阻断剂、玻璃体内注入抗新生血管药物、经瞳孔温热疗法、抗雄激素药物、甲氨蝶呤、利福平、褪黑激素等治疗方法的疗效。以上几种治疗方法的并发症少见, 但由于随访时间不同和招募的患者缺乏同质性, 导致难以比较不同治疗方法下患者的黄斑中心凹厚度的减少和最佳矫正视力的提高等疗效。本综述的目的是根据最新的临床试验结果, 对这种慢性疾病的治疗方案的管理进行全面的更新。.

The purpose of this study was to evaluate the efficacy and safety of combined phacoemulsification and Ex-PRESS implant with everting suture in primary angle-closure glaucoma (PACG) and to examine predictive factors of failure. Twenty-three eyes of 18 patients were enrolled. Data about time of removal of releasable sutures and traction of the everting suture and about changes in intraocular pressure (IOP) were collected, as well as comprehensive ophthalmic examinations. Success was defined by the following criteria: IOP ≤ 18 mmHg (criterion 1), IOP ≤ 15 mmHg (criterion 2), and IOP ≤ 12 mmHg (criterion 3). Success was categorized as complete or qualified, depending on whether it was reached without or with drugs, respectively. Success rate was assessed with Kaplan–Meier survival analysis with a Cox proportional hazard model to adjust for potential confounders. The lowering of IOP and the reduction of medications were statistically significant at every follow-up visit compared with the baseline (p &lt, 0.05). The complete success rates were 87%, 70%, and 17% accordingly to criterion 1, 2, and 3, the qualified success rates were 93%, 70%, and 20%, respectively. Most of the complications resolved spontaneously and conservatively. In conclusion, combined phacoemulsification and Ex-PRESS Minishunt implant with everting suture is a safe and effective surgery, even in PACG, lowering IOP and number of medications.

Objective Graves’ orbitopathy (GO) reflects an autoimmune response against antigens expressed by the thyroid and orbital tissues. Elimination of thyroid antigens may be beneficial for GO. Total thyroid ablation (TTA) [thyroidectomy (Tx), followed by 30 mCi of radioiodine] was shown to exert a beneficial effect on GO following intravenous glucocorticoids (ivGC) compared with Tx alone. Here, we investigated retrospectively whether TTA performed with a 15 mCi of radioiodine still maintains advantages over Tx. Methods Thirty-two subjects, 13 treated with TTA (performed with 15 mCi of radioiodine) and 19 with Tx alone, all with moderately severe, active GO, treated with ivGC, were studied. The primary objective was the outcome of GO at 24 weeks based on a composite evaluation. Results The two groups did not differ at baseline in terms of sex, age, smoking habits, TSH, anti-TSH receptor autoantibodies, GO duration and eye features. The proportion of GO responders at 24 weeks was greater in the TTA (61.5%) than in the Tx group (26.3%, P = 0.046). In contrast, GO outcome at 48 weeks did not differ between the two groups (69.2% vs 52.6% of responder in TTA and Tx group, respectively). The outcome of the individual GO features did not differ between the two groups both a 24 and 48 months. Conclusions The advantage of total thyroid ablation seems to be a more rapid response for GO to ivGC treatment. Prospective, randomized studies in a larger number of subjects are needed to confirm our findings.

To evaluate the effectiveness, treatment patterns and long-term safety of ranibizumab 0.5 mg in treatment-naïve patients with central retinal vein occlusion (CRVO) in a real-world setting.LUMINOUS, a 5-year, global, prospective, multicentre, multi-indication, observational, open-label study, recruited treatment naïve or prior treated patients who were treated as per the local ranibizumab label. Here, we report the mean change in visual acuity (VA; Early Treatment Diabetic Retinopathy Study [ETDRS] letters), treatment exposure over year (Y) 1 and 5-year safety in treatment-naïve CRVO patients.At baseline, the mean age of treatment-naïve CRVO patients (n = 327) was 68.9 years, with a mean (Standard deviation [SD]) VA of 40.6 (23.9) letters. At Y1, patients (n = 144) had a mean (SD) VA gain from baseline of 10.8 (19.66) letters, with a mean (SD) of 5.4 (2.65) ranibizumab injections. Patients demonstrated mean (SD) VA gains of 2.7 (19.35), 11.6 (20.56), 13.9 (18.08), 11.1 (18.46) and 8.2 (24.86) letters with 1, 2-3, 4-5, 6-8 and8 ranibizumab injections, respectively. Mean (SD) VA gains at Y1 in patients receiving loading (67.4%) and no loading dose (32.6%) was 11.9 (20.42) and 8.4 (17.99) letters, respectively. Over five years, the incidence of ocular/non-ocular adverse events (AEs) and serious AEs was 11.3%/8.6% and 1.2%/6.7%, respectively.These results demonstrate the effectiveness of ranibizumab in treatment-naïve CRVO patients at Y1 with clinically meaningful VA gains and no new safety findings over five years. These findings may help inform routine practice and enable better clinical management to achieve optimal visual outcomes.

Purpose The purpose of this paper is to present a new surgical technique to remove vitreous cortex remnants. Methods Non-consecutive retrospective interventional case series. Results When the posterior vitreous is split, its outermost layer may remain attached to the retina, developing vitreoschisis-induced vitreous cortex remnants (VCR). Their role in macular pathology etiopathogenesis has been well documented; however, recently, it has been proposed that VCR also play a crucial role in proliferative vitreoretinopathy and consequent retinal redetachment. The prevalence of VCR is underestimated because triamcinolone acetonide is not routinely used for vitreous staining. Vitreous cortex remnants (VCR) removal is challenging, and several surgical techniques have been proposed. However, they require sclerotomy enlargement, material that may not be readily available, and manual fashioning. Alternatively, a diamond-dusted membrane scraper (DDMS), already widely used in macular pathology treatment, can follow the contour of the retina, as it is a silicone tube, and remove VCR with its abrasive tip. A DDMS may also be introduced in the vitreous cavity through a standard trocar. Finally, the use of a DDMS provides predictable feedback, making the learning curve short. In this case series, 34 eyes affected by primary rhegmatogenous retinal detachment were enrolled. The retinal redetachment rate was 2.9% at six months of follow-up, below the average literature value of 21%. No adverse events were reported. Conclusion A DDMS can be suitable for use in VCR removal, although further studies are warranted to understand the indications and extent of this surgical technique for improving the management of rhegmatogenous retinal detachment.

Context Graves’ orbitopathy (GO) is an autoimmune disease that persists when immunosuppression is achieved. Orbital fibroblasts from GO patients display peculiar phenotypes even if not exposed to autoimmunity, possibly reflecting genetic or epigenetic mechanisms, which we investigated here. Objective We aimed to explore potential genetic or epigenetic differences using primary cultures of orbital fibroblasts from GO and control patients. Methods Cell proliferation, hyaluronic acid (HA) secretion, and HA synthases (HAS) were measured. Next-generation sequencing and gene expression analysis of the whole genome were performed, as well as real-time-PCR of selected genes and global DNA methylation assay on orbital fibroblasts from 6 patients with GO and 6 control patients from a referral center. Results Cell proliferation was higher in GO than in control fibroblasts. Likewise, HA in the cell medium was higher in GO fibroblasts. HAS-1 and HAS-2 did not differ between GO and control fibroblasts, whereas HAS-3 was more expressed in GO fibroblasts. No relevant gene variants were detected by whole-genome sequencing. However, 58 genes were found to be differentially expressed in GO compared with control fibroblasts, and RT-PCR confirmed the findings in 10 selected genes. We postulated that the differential gene expression was related to an epigenetic mechanism, reflecting diverse DNA methylation, which we therefore measured. In support of our hypothesis, global DNA methylation was significantly higher in GO fibroblasts. Conclusions We propose that, following an autoimmune insult, DNA methylation elicits differential gene expression and sustains the maintenance of GO.

Graves’ orbitopathy (GO) is the most common extrathyroidal manifestation of Graves’ disease (GD). Several studies support the involvement of TSH receptor autoantibodies (TRAbs) in the pathogenesis of GO, and a correlation between GO features and TRAbs has been reported, but not confirmed by all studies. Thus, we conducted a cross-sectional investigation to determine whether there is a correlation between TRAbs and the clinical features of GO in an initial phase of the eye disease. Ninety consecutive patients with untreated GO (67 women and 23 men, age 48.9 ± 12.6 years) were included. Patients who had received treatments other than anti-thyroid drugs for hyperthyroidism or lubricants for GO were excluded. All patients underwent an endocrinological and ophthalmological evaluation, the latter including exophthalmometry, measurement of eyelid width, clinical activity score (CAS), visual acuity, assessment of diplopia, and NOSPECS score. TRAb levels were measured by a third-generation competitive immunoassay. There was a statistically significant, direct correlation between serum TRAb levels and CAS by linear regression analysis (R = 0.278, P = 0.007). The correlation was confirmed by a multiple regression analysis (R = 0.285; P = 0.006) including age and FT3 levels, which also correlated with CAS. There were no relationships between TRAbs and exophthalmometry, eyelid aperture, degree of diplopia, visual acuity, and NOSPECS score. The levels of TRAb in subjects with a recent-onset, untreated GO are directly correlated with the clinical activity of the disease, confirming a possible role of these antibodies in the pathogenesis of GO.

The purpose of this paper is to provide a meaningful literature review about the epidemiology, pathogenesis, imaging and treatment of pachychoroid neovasculopathy (PNV). A computerized search from inception up to December 2019 of the online electronic database PubMed was performed using the following search string: “pachychoroid neovasculopathy”. The reference list in each article was scanned for additional relevant publications. PNV is a type-1 choroidal neovascularization, overlying focal areas of choroidal thickening and dilated choroidal vessels. It can develop in patients affected by pachychoroid pigment epitheliopathy or chronic central serous chorioretinopathy. The absence of drusen, the presence of pachydrusen, younger age of onset and choroidal thickening distinguish it from neovascular age-related macular degeneration (AMD). PNV incidence and prevalence data are lacking. Its pathophysiology is not fully understood, but angiogenic mechanisms involved in neovascular AMD may be different from those in PNV. Due to optical coherence tomography (OCT) improvements, PNV can be diagnosed more easily than before. In particular, PNV shows a shallow pigment epithelium detachment with an undulating retinal pigment epithelium over a subfoveal choroidal thickening, associated with vein enlargement in Haller’s layer (named pachyvessels) and choriocapillaris thinning. On OCT angiography, PNV reveals tangled hyper-reflective filamentous neovessels in the choriocapillaris itself. The current first-line PNV treatment is intravitreal anti-VEGF (vascular endothelial growth factor) injections with a treat-and-extend regimen. In particular, aflibercept shows a higher rate of fluid absorption than others. In the case of fluid recurrence or persistence, photodynamic therapy is a valid alternative. Ongoing research into pathophysiology and imaging improvements may be helpful in defining prognostic criteria and stratifying patient risk, allowing responsible monitoring and management of PNV.

Background: Refractory glaucoma still represents a challenge for ophthalmologists to manage intraocular pressure. The present study aimed to evaluate long term efficacy and safety of a second Ahmed valve implantation after the failure of a first implant in patients with refractory glaucoma and elevated intraocular pressure (IOP). Methods: Retrospective, multicenter non-comparative case series. Twenty-eight patients were retrospectively recruited between January 2011 and December 2017. Demographic data, glaucoma type, visual acuity, intraocular pressure, medical therapy, and complications were registered. Three criteria of success were established: Type 1 surgical success: IOP &le, 15 mmHg and a reduction of IOP &ge, 40% from baseline, Type 2 surgical success: IOP &le, 18 mmHg and a reduction of IOP &ge, 30% from baseline, and Type 3 surgical success: IOP &le, 21 mmHg and a reduction of IOP &ge, 20% from baseline. Surgical failure has been established as IOP less than 5 mmHg or over 21 mmHg and less than a 20% reduction of IOP from baseline despite medications in two consecutive visits, light perception loss referable to glaucoma, and the necessity for further glaucoma surgery. Failure was observed in six (21%) patients. (3) Results: Mean IOP and mean glaucoma medication number significantly reduced from baseline after the second implantation, and the surgical success rate at 72 months ranged from 10% to 78% based on the different criteria of success. Failure was observed in six (21%) patients. Conclusions: This study confirmed the safety and efficacy of a second Ahmed valve implantation in patients with refractory glaucoma and elevated IOP at baseline.

BACKGROUND/OBJECTIVES: To compare the efficacy of intraoperative localized and 360° laser retinopexy in cases of rhegmatogenous retinal detachment (RRD) treated with pars plana vitrectomy and air tamponade. SUBJECTS/METHODS: In this interventional, prospective, randomized, comparative study, 93 consecutive cases of RRD were enroled. After randomization 48 eyes received circumferential, while 45 underwent localized intraoperative laser retinopexy. Number and position of the retinal breaks, presence of proliferative vitreoretinopathy and/or lattice degeneration were recorded. Anatomical and visual outcome of the two groups were compared at 6 months postoperatively. RESULTS: Baseline characteristics did not significantly differ between groups. The single-operation reattachment rate was 86.66% in localized group and 89.58% in 360° group. The difference was not significant. (P = 0.46, χ(2) test). At 6 months postoperatively, visual acuity (logMAR) was 0.06 ± 0.05 in localized group and 0.05 ± 0.03 in 360° group. The difference was not statistically significant (P = 0.673, t-test). CONCLUSIONS: Localized laser resulted to be as effective as 360° laser application; this may lead some advantages in term of lower invasiveness, reduction risk of complications and time saving.

PURPOSE Ultrasound cycloplasty (UCP) acts through the selective coagulation of the ciliary body using high-intensity focused ultrasound (HIFU) technology. The aim of this study was to investigate whether the application of ultrasound beams targeting the ciliary body using an external probe influences astigmatism. METHODS Multicentre, prospective, single-arm, open-label study in adult patients with primary open-angle glaucoma and moderately uncontrolled intraocular pressure (IOP) under glaucoma medication. The primary outcome was induced corneal astigmatism, calculated from topography, and assessed statistically through vector analysis. Secondary outcomes included induced total astigmatism and mean changes from baseline in best-corrected visual acuity (logMAR) and IOP. Subgroup analysis was performed to assess the impact of device centring on corneal and total induced astigmatism. RESULTS Fifty eyes were enrolled. Mean age was 69.6 ± 11.3 years. At 1, 3 and 6 months postprocedure, HIFU-induced corneal astigmatism was 0.88 D × 93°, 0.87 D × 106° and 1.16 D × 97°, respectively, while induced total astigmatism was 0.62 D × 103°, 0.42 × 106° and 0.39 × 107°. By the last follow-up, the percentage of patients with

Purpose: To describe a new surgical technique for managing Ahmed Glaucoma Valve tube exposure. The technique is simple, safe, easy to perform and may be an interesting alternative to conventional covering of the tube. This technique allows unlike the classical ones to act on the cause and not only on the complication of extrusion. Materials and Methods: This study was a retrospective case series that included four eyes of four patients who presented with an Ahmed Glaucoma Valve tube exposure. Results: Surgery was uneventful in all cases and we did not observe any intraoperative or postoperative complications. After at least 1-year follow-up, no case of tube re-exposure was detected. Conclusions: Many techniques have been proposed in order to cover the extruded tubes, and different materials may be used to reinforce the coverage, but re-exposure of the tube is a possible scenario. Indeed, our technique attempts not only to cover the exposed tube but also to solve the cause of the extrusion.

Sub-macular hemorrhage (SMH) is a hematic collection between the neurosensory retina and the retinal pigment epithelium; one of its causes is ocular blunt trauma, that usually affects young patients. Persisting SMH leads to a damage of photoreceptors mediated by three main mechanisms: iron-related toxicity, impairment of diffusion of oxygen and nutriment, mechanical damage due to clot contraction. Since early photoreceptors’ damage has been reported within 24 h, it is suggested to provide an early treatment, although there are no guidelines or consensus between authors regarding treatment strategies. The aim of this review was to present and compare available treatment options, like intravitreal tissue plasminogen activator (tPA) associated with pneumatic displacement, pneumatic displacement alone, subretinal tPA injection with pneumatic displacement, and intravitreal anti-vascular endothelial growth factor (VEGF) injection. All procedures obtained consistent results, though the most effective seemed to be pars plana vitrectomy, subretinal tPA and gas tamponade, probably due to a quicker liquefaction and displacement of the clot. Limitations concern the greater invasiveness and the higher incidence of complications. Alternatively, intravitreal injection of tPA and gas may represent a less invasive option with fewer complications. Intravitreal injection of gas and prone position could be preferred in young patients without coexisting ocular pathology, being a minimally invasive treatment, with lower risk of complications and a good visual recovery. Anti-VEGF agent have found, to date, limited employment in cases of traumatic SMH even though they may be useful as alternative or adjuvant therapy. Most of the published literature consists of small studies and case reports, therefore further investigations and larger clinical trials are required to fully understand safety and efficacy of the procedures. A preoperative comprehensive evaluation may be helpful to realize a surgical plan tailored on patient.

Limited data suggest that treatment with statins is associated with a reduced risk of Graves' orbitopathy (GO) in patients with Graves' disease (GD), attributed to the anti-inflammatory rather than to the hypolipemic effects of these medications. The aim of the present study was to investigate whether there is an association between high cholesterol and GO. The primary outcome was the relation between GO and low-density lipoprotein (LDL)-cholesterol. The secondary outcomes were the relation between severity or activity (the clinical activity score [CAS]) of GO and LDL-cholesterol.A cross-sectional investigation was conducted in consecutive patients with GD who came under the authors' observation to undergo radioiodine treatment, a stratification aimed at forming two distinct groups of patients under the same conditions. A total of 250 patients were enrolled, 133 with and 117 without GO. Ophthalmological assessments and serum lipids measurements were performed.In multivariate analyses with correction for the duration of hyperthyroidism, a variable that differed between patients with respect to the presence or absence of GO, a correlation between the presence of GO and both total (p = 0.01) and LDL-cholesterol (p = 0.02) was observed. In patients with hyperthyroidism lasting44 months, total and LDL-cholesterol were higher (p = 0.01 and p = 0.008, respectively) among GO patients. In this subgroup, based on the presence/absence of GO, cutoff values were established for total (191 mg/dL) and LDL-cholesterol (118.4 mg/dL), above which an increased risk of GO was observed (total cholesterol relative risk: 1.47; p = 0.03; LDL-cholesterol relative risk: 1.28; p = 0.03). GO severity and CAS did not correlate with serum lipids. However, CAS was found to be higher (p = 0.02) in patients with high total cholesterol. When the analysis was restricted to untreated GO patients, a correlation was found between CAS and both total (p = 0.04) and LDL-cholesterol (p = 0.03), after adjustment for GO duration.In patients with a short duration of hyperthyroidism, total and LDL-cholesterol correlate with the presence of GO, suggesting a role of cholesterol in the development of GO. Depending on GO duration, total and LDL-cholesterol correlate with GO activity, suggesting a role of cholesterol in the clinical expression of GO.

Background: The purpose of this prospective study was to evaluate the efficacy and safety of the Ultrasound Cyclo Plasty (UCP) procedure using high-intensity focused ultrasound in surgery-naïve open-angle glaucoma patients. Methods: prospective, non-randomized, single-arm, multicenter clinical trial. Sixty-six eyes with primary open-angle glaucoma, intraocular pressure (IOP) ≥21 mmHg and with no history of filtering surgery were enrolled. Patients were treated by UCP with a therapy probe comprising six piezoelectric transducers, consecutively activated for 8 s each. Complete ophthalmic examination was performed before the procedure, 1 day after the procedure, and 1, 3, 6, 12, 18 and 24 months after the procedure. Primary outcomes were complete success (defined as IOP lowering from baseline ≥20% without additional glaucoma medications) and vision-threatening complications. Secondary outcomes were the presence of complications and the reduction of the number of medications used. Results: IOP was significantly reduced after one procedure (p &lt, 0.05), from a mean pre-operative value of 24.3 ± 2.9 mmHg (n = 2.3 hypotensive medications) to a mean value of 15.9 ± 3.6 mmHg (n = 2.2 hypotensive medications) at 2 years (mean IOP lowering of 33%). Surgical success was achieved in 74% of eyes. Notwithstanding side effects such as transient anterior chamber inflammation, refractive error changes, transient hypotony and macular edema, no major intra or post-operative complications such as phthisis, induced cataract, neovascularization or significant vision loss were observed. Conclusions: Ultrasound Cyclo Plasty is a valuable, effective and well-tolerated procedure to lower IOP in patients with open-angle glaucoma without previous filtering surgery.

The supraciliary space is a physiological route for aqueous humor outflow located anteriorly between the outer surface of the ciliary body and the internal surface of the sclera. Posteriorly, the suprachoroidal space is located between the choroid and the internal surface of the sclera. These spaces have been targeted as suitable and helpful pathways for glaucoma treatment, alternatives to the traditional subconjunctival space. The subconjunctival surgical pathway is affected by several limitations such as poor cosmesis, a lifetime risk for endophthalmitis, and an unpredictable wound healing response. Because of these limitations, the supraciliary space has gained growing interest as a possible target for new glaucoma drainage devices such as: Gold Micro Shunt (SOLX Inc.; Waltham, MA, USA), iStent Supra (Glaukos Corporation, Laguna Hills, CA, USA), CyPass Micro-Stent (Transcend Medical Inc., Menlo Park, CA, USA), Aquashunt (OPKO health Inc., Miami, FL, USA), STARflo (iSTAR Medical, Isnes, Belgium), and Esnoper-Clip implant (AJL Ophthalmics, Álava, Spain). We review the current literature concerning the supraciliary space to evaluate its safety and efficacy as a suitable pathway for glaucoma surgical treatment.

Oxidative stress is involved in the pathogenesis of Graves’ orbitopathy (GO) and an antioxidant approach has been advocated for GO treatment. Here, we investigated the action of three antioxidants in orbital fibroblasts, namely, vitamin C, N-acetyl-l-cysteine, and melatonin. Primary cultures of orbital fibroblasts from six GO patients and six control subjects were established. Cells were treated with H2O2 to induce oxidative stress. Cell vitality assays were performed to determine the non-cytotoxic dose of each antioxidant. The following assays were performed: glutathione disulfide (GSSG), as a measure of oxidative stress, cell proliferation, hyaluronic acid (HA), TNFα, IFNγ, and IL1β. H2O2 induced oxidative stress (augmented GSSG), increased cell proliferation as well as cytokine release, but did not affect HA release. All of the three antioxidant substances reduced H2O2-dependent oxidative stress. Vitamin C reduced proliferation in GO, but not in control fibroblasts. N-acetyl-l-cysteine reduced proliferation and IFNγ in GO, and HA and IL1β in both GO and control fibroblasts. Melatonin reduced IL1β and HA in GO and control fibroblasts, and IFNγ only in GO fibroblasts. Our study provides evidence in support of an antioxidant role of vitamin C, N-acetyl-l-cysteine and melatonin in orbital fibroblasts. Some of the effects of these compounds are exclusive to GO fibroblasts, whereas some other are observed also in control fibroblasts. Our observations provide a basis for a possible clinical use of these substances in patients with GO.

Glaucoma, one of the leading causes of blindness, is usually first managed medically, with incisional surgery as a second step. Noninvasive glaucoma procedures attempt to fill the gap between medical and surgical treatments and may work synergistically with them. High-intensity focused ultrasound induces a selective and controlled thermal ablation of the distal part of the ciliary body, and this effect is independent from the degree of tissue pigmentation with limited damage to adjacent structures. This selective and innovative treatment decreases intraocular pressure by reducing aqueous humor production and by increasing uveoscleral outflow. We review the current literature on the use of high-intensity focused ultrasound in glaucoma, exploring present use, safety, efficacy, and future clinical applications.

Intravenous (iv) glucocorticoids (GC) (ivGC) are used for active Graves orbitopathy (GO), but factors affecting GO outcome are poorly understood. We performed a retrospective study to investigate the variables affecting GO after ivGC.We evaluated 83 consecutive GO patients treated with ivGC but not orbital radiotherapy (ORT) and re-examined them after a median of 47 months. The endpoints were the relationships between GO outcome or additional treatments with age, sex, smoking habits, thyroid volume, thyroid treatment, time since thyroid treatment, antithyroid-stimulating hormone receptor antibodies (TRAb), GO duration, GO features, and follow-up time.GO features improved after treatment, resulting in moderate and marked amelioration in ~75% and ~41% of patients respectively. By multivariate analysis, a moderate GO improvement correlated with diplopia at first observation, which was more severe in responders. A marked GO improvement correlated with time between first and last observation and time after thyroid treatment, which were longer in responders. This likely reflected the combination of an early effect of GC and a late, spontaneous improvement of GO, as shown by analyses of GO outcome at various time points. Additional treatments after ivGC correlated by multivariate analysis with eyelid aperture, diplopia and NOSPECS score (NOSPECS stands for no GO signs [N], only eyelid sign [O], soft tissue involvement [S], proptosis [P], extraocular motility restriction [E], corneal involvement [C], and sight loss [S]) at first observation, which were more severe in responders.Our study shows that response to ivGC increases with time, likely reflecting the known tendency of GO to improve spontaneously, and is more pronounced when GO is more severe to begin with, which is associated with more additional treatments.ANOVA = analysis of variance CAS = clinical activity score GC = glucocorticoids GO = Graves orbitopathy

L'obiettivo di questo studio è analizzare le complicanze della decompressione orbitaria in pazienti affetti da oftalmopatia Basedowiana. Abbiamo analizzato 946 pazienti sottoposti a decompressione orbitaria per orbitopatia di Graves e le complicanze intra- e post-operatorie con un follow-up minimo di 6 mesi. Abbiamo eseguito inoltre un'estesa revisione della letteratura per comparare i risultati. Nel nostro studio le più frequenti complicanze sono state: atrofia della regione temporale (100%) nei pazienti sottoposti a decompressione con approccio coronale; ipoestesia permanente di V2 (13%) e V1 (8%) in pazienti sottoposti a decompressione con approccio transpalpebrale superiore. Un solo paziente ha avuto una lesione totale monolaterale di V2. Le complicanze più gravi sono state la riduzione dell'acuità visiva, che si è verificata in 5 pazienti, e la perdita di liquido cerebrospinale con complicanze cerebrali, verificatesi in 2 pazienti, entrambi operati con approccio endonasale non endoscopico. 3 pazienti hanno avuto un'emorragia intraoperatoria mentre 3 pazienti un'emorragia postoperatoria che ha richiesto un secondo intervento chirurgico. L'incidenza delle sinusiti/mucoceli sintomatici è stata dello 0,75%. In conclusione abbiamo evidenziato come la decompressione orbitaria eseguita con tecnica endoscopica endonasale e con accessi transpalpebrali sia una procedura chirurgica con una bassa incidenza di complicanze. La conoscenza delle cause delle possibili complicanze nei differenti approcci chirurgici può sicuramente aiutare a ridurre la loro incidenza.

PURPOSE: To evaluate the effectiveness of an ab interno subconjunctival gelatin implant as primary surgical intervention in reducing intraocular pressure (IOP) and IOP-lowering medication count in medically uncontrolled moderate primary open-angle glaucoma (POAG). METHODS: In this prospective, non-randomized, open-label, multicenter, 2-year study, eyes with medicated baseline IOP 18-33 mmHg on 1-4 topical medications were implanted with (phaco + implant) or without (implant alone) phacoemulsification. Changes in mean IOP and medication count at months 12 (primary outcomes) and 24, clinical success rate (eyes [%] achieving ≥ 20% IOP reduction from baseline on the same or fewer medications without glaucoma-related secondary surgical intervention), intraoperative complications, and postoperative adverse events were assessed. RESULTS: The modified intent-to-treat population included 202 eyes (of 218 implanted). Changes (standard deviation) in mean IOP and medication count from baseline were - 6.5 (5.3) mmHg and - 1.7 (1.3) at month 12 and - 6.2 (4.9) mmHg and - 1.5 (1.4) at month 24, respectively (all P

Sir,Giant cell arteritis (GCA) is a systemic inflammatory vasculitis of the elderly, that usually involves large and medium sized arteries [1]. Extracranial branches of the carotid artery are commo...

It has been suggested that high cholesterol represents a risk factor for Graves’ orbitopathy (GO). In a recent cross-sectional study, a correlation between cholesterol and the presence of GO was found in patients with a Graves’ disease (GD) of recent onset. To confirm this observation, we conducted a retrospective investigation in consecutive patients with GD. The primary outcome was the relationship between the presence of GO and low-density lipoprotein (LDL)-cholesterol. The design entailed the inclusion of consecutive patients with a GD of recent onset, with or without GO, who came to our observation to receive radioiodine over a period of 6 months, and a stratification aimed at having two homogeneous group of patients in terms of thyroid function. A total of 86 patients fulfilled the inclusion and evaded the exclusion criteria. All patients underwent an ophthalmological assessment and serum lipids were measured. Serum levels of LDL-cholesterol were significantly higher in patients with GO (135.3 ± 41.3 mg/dL) compared with those without GO (106.6 ± 23.9 mg/dL, P = 0.0007). In a similar manner, serum levels of total cholesterol were higher in patients with GO (211.6 ± 44.0 mg/dL) than in those without GO (176.0 ± 27.2 mg/dL, P = 0.0001). There was no relationship between GO severity and activity and cholesterol. There was no relationship between GO and high-density lipoprotein-cholesterol or triglycerides. Our study confirms a relationship between the presence of GO and cholesterol in patients with GD of recent onset. Whether lowering of cholesterol ameliorates, GO remains to be established.

Purpose To report a case of postsurgical shallow anterior chamber and elevated intraocular pressure (IOP) simulating malignant glaucoma. Methods A 20-year-old woman underwent EX-PRESS® device implant for treatment of primary open-angle glaucoma. Results Postoperative examination showed a shallow anterior chamber, the EX-PRESS® device embedded in the iris, an IOP of 28 mm Hg, and an annular detachment of the choroid ciliary body, suggesting hyperfiltration followed by EX-PRESS® blockage. The anterior chamber was restored using an ophthalmic viscoelastic and an additional suture was applied ensuring the scleral flap. The IOP progressively decreased in the following days and the anterior chamber remained deep and stable. New ocular ultrasonography showed complete resolution of the ciliary body detachment 15 days after surgery. Conclusions After glaucoma surgery, not every patient with shallow anterior chamber and normal or high IOP necessarily has a ciliary block glaucoma. In our case, hyperfiltration led to choroidal expansion, shallow anterior chamber, obstruction of the EX-PRESS®, and secondary blockage of outflow. The differential diagnosis is important in order to avoid further invasive procedures (i.e., lensectomy or vitrectomy).

BACKGROUND/AIMS: The epidemiology of Graves' orbitopathy (GO) may be changing. The aim of the study was to identify trends in presentation of GO to tertiary centres and initial management over time.METHODS: Prospective observational study of European Group On Graves' Orbitopathy (EUGOGO) centres. All new referrals with a diagnosis of GO over a 4-month period in 2012 were included. Clinical and demographic characteristics, referral timelines and initial decisions about management were recorded. The data were compared with a similar EUGOGO survey performed in 2000.RESULTS: The demographic characteristics of 269 patients studied in 2012 were similar to those collected in the year 2000, including smoking rates (40.0% vs 40.2%). Mild (60.5% vs 41.2%, pCONCLUSIONS: These findings suggest that the clinical manifestations of patients with GO may be changing over time in Europe.

Oxidative stress is involved in the pathogenesis of Graves’ orbitopathy (GO) and several antioxidant agents, namely, selenium, quercetin, enalapril, vitamin C, N-acetyl-l-cysteine, and melatonin, have been shown to reduce oxidative stress and its consequences in primary culture of orbital fibroblasts. In addition, selenium is effective for the treatment of mild GO. Here, we investigated the action of three additional antioxidants in orbital fibroblasts, namely, retinol, β-carotene, and vitamin E. Primary cultures of orbital fibroblasts were established from GO patients and control subjects. To induce oxidative stress, cells were treated with H2O2, after which glutathione disulfide (GSSG) (a parameter of oxidative stress), cell proliferation, hyaluronic acid, TNFα, IFNγ, and IL1β were measured. H2O2-dependent oxidative stress (augmented GSSG) was associated with increased cell proliferation and cytokine release. All the three antioxidant substances reduced GSSG in both GO and control fibroblasts. β-carotene reduced proliferation in GO, but not in control fibroblasts. IL1β was reduced by all three substances. Retinol reduced IFNγ in GO and control fibroblasts. Our study supports an antioxidant role of retinol, β-carotene, and vitamin E in orbital fibroblasts from patients with GO and provides a basis for a possible clinical use these substances.