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BackgroundThough several procedures of IOL implantation have been described (sutured scleral fixation, intra-scleral fixation, angle-supported anterior chamber, and anterior chamber or retropupillary iris-claw IOLs), there are no randomized trials which are comparing different techniques. Hence, the surgical treatment of aphakia still remains controversial and challenging. The purpose of this study was to compare the long-term efficacy and the rate of complications of anterior versus posterior Iris-claw intraocular lenses (IOL) implantation to correct for the treatment of aphakia without sufficient capsule support.Methods and findingsConsecutive eyes having secondary implantation of aphakic iris-fixated IOLs with a follow-up of at least 5 years were considered. Mean correct distance visual acuity (CDVA) changes, percentage of eyes with CDVA improvement, mean corneal endothelial cell density (CECD) loss and the rate of other complications were used for statistical analysis. The study evaluated a total of 180 eyes (Group A: 87 anterior chamber iris-claw fixation, Group B: 93 retropupillary iris-claw implantation) of 180 consecutive different patients, with aphakia of various reasons. CDVA improved significantly in both groups after surgery (PConclusionsFive-year follow-up shows that secondary implantation of aphakic IOLs is effective and safe for the correction treatment of aphakia in eyes without capsule support.

Purpose: To analyse the effects of intravitreal dexamethasone implant (DEX) in patients with diabetic macular oedema (DME) unresponsive to ranibizumab treatment, in relation to the inflammatory optical coherence tomography (OCT) retinal features, subfoveal neuroretinal detachment (SND) and hyperreflective retinal spots (HRS). Methods: Patients with DME poorly responsive to three injections of ranibizumab were treated with DEX. Best-corrected visual acuity (BCVA) and central macula thickness (CMT, measured by Spectralis SD-OCT) were assessed at baseline and at 1, 3, and 6months. Results: Overall, 44 eyes were included in the study. In the whole group, mean BCVA (baseline 51.5±8.3 letters) increased significantly at 1month (to 56.9±8.8 letters; Tukey HSD p=0.017) and was 55.5±8.8 letters at 3months (Tukey HSD p=0.128). Central macula thickness (CMT) reduced significantly at 1 and 3months (417±149μm and 469±128μm, respectively, both Tukey HSD p&nbsp

Purpose: To analyse the postoperative foveal avascular zone (FAZ) area, superficial vessel density (SVD) and deep vessel density (DVD) and their correlation with functional (best-corrected visual acuity, BCVA) and anatomical outcomes (foveal macular thickness, FMT) after surgery for rhegmatogenous retinal detachment (RRD) repair. Method: Patients with RRD eyes, successfully treated with a single pars plana vitrectomy (PPV) with gas tamponade and a minimum 12months follow-up, were re-examined. Foveal avascular zone (FAZ) area, SVD, DVD and FMT were evaluated by using optical coherence tomography angiography (OCTA) and compared to fellow eye. Results: Fifty-six patients with macula-on and 37 with macula-off RRD were included in the study. In both groups, no difference in FMT and FAZ area was found compared to fellow eyes. In macula-on RRD eyes, a lower parafoveal DVD (p=0.001) was detected; FAZ area was related to FMT (p=0.025), and the postoperative BCVA was correlated with parafoveal DVD (p=0.010) and FAZ area (p=0.003). In macula-off RRD eyes, lower parafoveal SDV (p=0.012), and foveal and parafoveal DVD (p=0.012 and p&nbsp

Postoperative nausea and vomiting (PONV) after vitreoretinal surgery may potentially be associated with severe complications, such as suprachoroidal hemorrhage. The purpose of the present multicenter clinical trial (NCT02386059) was to assess the efficacy of three different prophylactic treatments for PONV after vitrectomy under local anesthesia. Patients undergoing primary vitrectomy were randomized to the control arm or to one of the treatment arms (4 mg ondansetron, 4 mg dexamethasone, combination of the two drugs). The primary outcome measure was the proportion of complete response (no nausea, no vomiting, no retching, and no use of antiemetic rescue medication) during 24 h after vitrectomy. Secondary outcomes included the severity standardized score of PONV, postoperative pain standardized score, and rate of ocular and non-ocular adverse events. Baseline demographics of the 1287 patients were comparable between the four arms. The combined therapy group showed a statistically significant lower incidence of PONV compared to the placebo and monotherapy (p &lt, 0.001). PONV severity was also reduced in the combination group compared to the others (p &lt, 0.001). Postoperative pain scores and adverse events were comparable among the four groups. Combined therapy with dexamethasone and ondansetron was the most effective treatment for reducing the incidence and severity of PONV in patients undergoing vitrectomy under local anesthesia.

MacroH2A is a histone variant whose expression has been studied in several neoplasms, including cutaneous melanomas (CMs). In the literature, it has been demonstrated that macroH2A.1 levels gradually decrease during CM progression, and a high expression of macroH2A.1 in CM cells relates to a better prognosis. Although both uveal and cutaneous melanomas arise from melanocytes, uveal melanoma (UM) is biologically and genetically distinct from the more common cutaneous melanoma. Metastasis to the liver is a frequent occurrence in UM, and about 40%&ndash, 50% of patients die of metastatic disease, even with early diagnosis, proper treatment, and close follow-up. We wanted to investigate macroH2A.1 immunohistochemical expression in UM. Our results demonstrated that mH2A.1 expression was higher in metastatic UM (21/23, 91.4%), while only 18/32 (56.3%). UMs without metastases showed mH2A.1 staining. These data could suggest a possible prognostic role for mH2A.1 and could form a basis for developing new pharmacological strategies for UM treatment.

Uveal Melanoma (UM) represents the most common primary intraocular malignant tumor in adults. Although it originates from melanocytes as cutaneous melanoma, it shows significant clinical and biological differences with the latter, including high resistance to immune therapy. Indeed, UM can evade immune surveillance via multiple mechanisms, such as the expression of inhibitory checkpoints (e.g., PD-L1, CD47, CD200) and the production of IDO-1 and soluble FasL, among others. More in-depth understanding of these mechanisms will suggest potential targets for the design of novel and more effective management strategies for UM patients.

The corneal endothelium is composed of a single hexagonal-shaped cells layer adherent to the Descemet's membrane. The primary function of these cells is maintaining of tissue clarity by regulating its hydration. Trauma, aging or other pathologies cause their loss, counterbalanced by enlargement of survived cells unable to guarantee an efficient fluid pumping to and from the stroma. Regenerative medicine using human corneal endothelial cells (HCECs) isolated from peripheral corneal-scleral tissue of a donor could be an attractive solution, overcoming transplantation problems. In a previous study, we have demonstrated that HCECs treatment with pituitary adenylate cyclase-activating polypeptide (PACAP) following growth factors deprivation prevents their degeneration. However, the molecular mechanism mediating this effect has not been clarified, yet. Here, we have shown for the first time the expression of PACAP and its receptor (PAC1R) in human corneal endothelium and demonstrated that this peptide, selectively binding to PAC1R, induces epidermal growth factor receptor (EGFR) phosphorylation and the MAPK/ERK1/2 signaling pathway activation. In conclusion, our data have suggested that PACAP could represent an important trophic factor in maintaining human corneal endothelial integrity through EGFR transactivation. Therefore, PACAP, as well as epidermal growth factor and fibroblast growth factor, could co-operate to guarantee tissue physiological functioning by supporting corneal endothelial barrier integrity.

Uveal melanoma is a rare disease but it is the most common primary intraocular malignant tumor in adults with poor late prognosis. About 50% of patients will develop liver metastasis far from the enucleation within 10–15 years. Our study examined SPANX-C expression levels in primary uveal melanoma both with and without metastasis to assess if they can be used to predict metastasis. This study included a total of 55 patients, 28 males and 27 females, with uveal melanoma. A significantly high expression of SPANX-C was seen in 19/23 (82.6%) patients with metastasis, and only in 11/32 (38.5%) patients without metastasis. In conclusion, we found that SPANX-C expression could play a role in tumor progression of uveal melanoma.

Uveal melanoma (UM) is the most common primary intraocular cancer in adults. In the present study, we aimed to characterize the immunological features of primary UM cancer and to provide an association with prognostic markers and outcome. Also, we assessed the influence of the microenvironment on the expression of inhibitory immune checkpoints in UM. Genes of interest included MHC Class I and Class II molecules, as well as inhibitory immune-checkpoints, i.e. PDL1, PDL2, B7-H3, B7-H4, TBFRSF6B, CD47, CD155, GAL9, HVEM and CD200. We observed significant lower levels of MHC genes in UM cells as compared to normal uveal melanocytes. Unexpectedly however, the expression levels of most of the analyzed inhibitory immune-checkpoint genes were not different in cancer cells as compared to normal melanocytes, with the exception of CD200 and HVEM, that resulted significantly reduced. On the other hand, PDL1 inversely correlated with OS, PFS and thickness of the tumor. Also, PDL1, along with PDL2, expression significantly increased under inflammatory conditions. Finally, for the first time, we propose a possible role for CD47 in the immune evasive properties of UM. We show here that CD47 is significantly upregulated by UM cells following inflammatory stimuli and that it represents a good independent predictor of disease progression. The results from this study may propel advances in the development of immune-based therapies for UM patients.

Uveal melanoma is the most frequent primary intraocular neoplasm in adults. Although malignant melanoma may be located at any point in the uveal tract, the choroid and ciliary body are more frequent locations than the iris. In the present study, we examined ADAM10 expression levels in primary uveal melanoma both with and without metastasis, and we evaluated their association with other high risk characteristics for metastasis in order to assess if ADAM10 can be used to predict metastasis. This study included a total of 52 patients, 23 men and 29 women, with uveal melanoma. A significantly high expression of ADAM-10 was seen in patients with metastasis (11/13, 84.6%), but not in patients without metastasis (15/39, 38.5%). In conclusion we found that ADAM10 expression was associated with a more rapid metastatic progression confirming its role in uveal melanoma metastasis.

Objective To report cases of acute serous macular detachment and edema after uncomplicated phacoemulsification. Design Retrospective case series. Participants We reviewed the clinical data of 5 patients who developed an acute serous macular detachment and edema after uncomplicated phacoemulsification with intraocular lens implantation by the same expert surgeon and without any complication during surgery. Methods Best corrected visual acuity (BCVA), biomicroscopy, fundus examination, and optical coherence tomography were performed at 1, 3, 7, and 30 postoperative days. Results On the first postoperative day, all eyes had low visual acuity (median 1.0 logMAR) despite normal postoperative appearance of the anterior segment. Optical coherence tomography showed serous macular detachment with intraretinal fluid accumulation. After treatment with oral indomethacin and acetazolamide, at 7 days, intraretinal and subretinal fluid were fully reabsorbed and BCVA improved (at least 0.1 logMAR). In the following 6 months, no eye had recurrence of macular edema. Conclusions Acute serous macular detachment and edema can occur after uncomplicated phacoemulsification. It should be considered in cases of low visual acuity during the early postoperative period.

Background: Since the efficacy of ranibizumab (RBZ), bevacizumab (BVZ) and aflibercept (AFB) is comparable in neovascular age-related macular degeneration (AMD), we conducted a systematic review and meta-analysis to evaluate the long-term safety profiles of these agents, including ocular safety. Methods: Systematic review identifying randomized controlled trials (RCTs) comparing RBZ, BVZ and AFB directly published before March 2019. Serious ocular adverse events (SOAE) of special interest were endophthalmitis, pseudo-endophthalmitis, retinal pigment epithelium tear and newly identified macular atrophy. Results: Thirteen RCTs selected for meta-analysis (4952 patients, 8723 people-years follow-up): 10 compared RBZ vs. BVZ and three RBZ vs. AFB. There were no significant differences in almost all adverse events (systemic and ocular) between BVZ, RBZ and AFB in up to two years’ follow-up. Macular atrophy was reported heterogeneously and not reported as SOAE in most trials. Conclusions: Direct comparison of RBZ, BVZ and AFB safety profiles in the RCT network meta-analytical setting have not revealed a consistent benefit of these three commonly used anti-vascular endothelial growth factor (anti-VEGF) agents in AMD. Network model ranking highlighted potential benefits of RBZ in terms of a systemic safety profile; however, this appears a hypothesis rather than a conclusion. Newly identified macular atrophy is underestimated in RCTs—future real-world data should be focused on SOAE.

To estimate the incidence of acute cerebral ischaemia detected by magnetic resonance imaging (MRI) in acute central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO) and transient monocular vision loss (TMVL).Studies reporting the incidence of acute cerebral ischaemia, detected by MRI, within 7 days from diagnosis of acute CRAO, BRAO and TMVL up to January 2019 were systematically searched for on Pubmed, Medline and Cochrane Library. Meta-analysis was performed using random effects model. The primary outcome was the pooled estimate of incidence of acute cerebral ischaemia in CRAO, BRAO and TMVL cohorts including both neurologically symptomatic and asymptomatic patients, expressed as a proportion along with 95% confidence intervals (CIs). The pooled estimate of incidence of asymptomatic acute cerebral ischaemia represented a secondary outcome measure.For the primary outcome, the pooled proportion of acute cerebral ischaemia was 0.30 (CI 0.24-0.36) in the CRAO cohort, and 0.25 (CI 0.16-0.37) in the BRAO cohort, without statistical heterogeneity. The rate of acute cerebral ischaemia was 11.8% in the TMVL cohort. For the secondary outcome, the pooled proportion of asymptomatic acute cerebral ischaemia was 0.22 (CI 0.16-0.28) in the CRAO cohort, 0.29 (CI 0.20-0.41) in the BRAO cohort and 0.08 (CI 0.05-0.15) in the TMVL cohort, with no statistical heterogeneity.30% of patients with acute CRAO and 25% of patients with acute BRAO presented an acute cerebral ischaemia on MRI. Such high rates support a care pathway of prompt referral of such patients for neurological evaluation and brain imaging.

Purpose: To assess the efficacy of intravitreal aflibercept in patients suffering from post-radiation macular edema following plaque radiotherapy for choroidal melanoma. Methods: This prospective, interventional case series included patients affected by radiation maculopathy (RM) with macular edema secondary to ruthenium-106 plaque brachytherapy for choroidal melanoma. The effect of intravitreal aflibercept on best-corrected visual acuity (BCVA), central foveal thickness (CFT) detected by spectral domain optical coherence tomography (sd-OCT), and Horgan’s grading scale of RM was evaluated throughout the 24-month follow-up. Intraocular pressure (IOP) and possible complications were also recorded. Results: Nine eyes of 9 patients were included. A mean of 4.4 ± 1.2 injections were given over the 24 months. At the end of follow-up, mean BCVA was significantly improved, from 0.9 ± 0.19 logMAR at baseline to 0.56 ± 0.3 logMAR (P = 0.028), and mean CFT was significantly decreased, from 546 ± 123 μm at baseline to 223 ± 34 μm (P < 0.001). Intravitreal aflibercept lowered baseline maculopathy stage as well. No significant change in IOP values and no complications, such as endophthalmitis, was recorded. Conclusion: Intravitreal aflibercept is an effective treatment for patients with radiation-induced macular edema, allowing functional and anatomical improvements to be achieved with a relatively low number of injections.

Purpose: To evaluate the response to anti–vascular endothelial growth factor therapy for choroidal neovascularization secondary to choroidal osteoma using optical coherence tomography angiography. Methods: This retrospective study included four eyes of four females with choroidal osteoma complicated by choroidal neovascularization, treated with ranibizumab. All patients underwent full ophthalmologic examination, including ocular ultrasound, retinography, fluorescein angiography, spectral-domain or swept-source optical coherence tomography, and optical coherence tomography angiography. These images were analyzed to measure choroidal osteoma and to study choroidal neovascularization changes after intravitreal anti–vascular endothelial growth factor. Results: In all cases, fluorescein angiography revealed the presence the choroidal neovascularization, as an early hyperfluorescence area increasing during the exam. Optical coherence tomography showed both the choroidal osteoma and choroidal neovascularization and intra- or subretinal fluid as activity sign. In optical coherence tomography angiography, choroidal osteoma vessels were valuable in outer retina and choroidal slabs, and were irregular and did not change after ranibizumab injection; neovascular network correlating with choroidal neovascularization showed a hyperflow tangled vessels in outer retina, decreasing in density after anti–vascular endothelial growth factor therapy. Conclusion: Optical coherence tomography angiography seems to be a useful tool in visualizing and distinguishing vascular networks of choroidal osteoma and of choroidal neovascularization secondary to choroidal osteoma better than fluorescein angiography.

In order to investigate Insulin-like growth factor-1 (IGF-1) blood levels in male and female age-matched patients affected by early, intermediate, neovascular age related macular degeneration (AMD) and healthy subjects (no AMD) were enrolled in a prospective, observational study. All patients enrolled were classified according to 4 stages classification of AMD from Age-related eye disease study (AREDS). Each subject underwent a complete ophthalmic examination including best corrected visual acuity (BCVA), applanation tonometry, slit-lamp biomicroscopic examination, color fundus photography, optical coherence tomography (OCT) and, if needed, fluorescein angiography. Overall, 224 anti-VEGF naive subjects including 56 patients in early AMD group, 56 patients in intermediate AMD group, 56 patients in neovascular AMD group and 56 patients in no AMD group were recruited. For each group 28 male patients and 28 female patients were enrolled. IGF-1 hematic levels were significantly higher (p

Cornea’s posterior surface includes endothelium maintaining stromal hydration and clarity. Due to their limited proliferative capability, the loss of endothelial cells can outcome in permanent opacity. In the last years, different studies have demonstrated the protective effect of pituitary adenylate cyclase-activating polypeptide (PACAP) in different ocular diseases. However, its role on human corneal endothelial cells (HCECs) has not been investigated, yet. Here, we have developed a culture protocol to differentiate HCECs from donor’s cornea. PACAP treatment prevented damage induced by growth factors deprivation of cells grown on transwell supports as revealed by TERR measurements. Moreover, this peptide significantly increased tight junction proteins expression by conferring resistance to endothelial barrier. This effect is also related to promotion of cell viability as demonstrated by MTT assay. Furthermore, PACAP stimulated repairing of corneal endothelium lesion as shown by wound healing analysis. In conclusion, our data suggest that this peptide could represent an important trophic factor in maintaining functionality of human corneal endothelium.

Purpose: To determine the incidence and risk factors for late-onset ocular hypertension (LOH) after vitrectomy. Methods: From the electronic medical records of consecutive patients who underwent primary vitrectomy, from January 2010 to December 2015, at 5 tertiary vitreoretinal centers in Italy, patient demographics, systemic, ophthalmic, operative, and postoperative data were drawn. Main outcome measure was the presence of LOH, defined as intraocular pressure >21 mmHg detected more than 2 months after vitrectomy on at least 2 consecutive visits. Results: Among 6,048 patients, LOH was found in 294 (4.9%) vitrectomized eyes and in 87 (1.4%) fellow eyes, (chi square; P < 0.001). Multivariable logistic regression showed that significant risk factors for developing LOH included intraoperative triamcinolone use (odds ratio [OR], 7.62; P < 0.001), longer axial length (OR, 1.55; P = 3.023), preoperative higher intraocular pressure (OR, 1.81; P = 0.003), and postvitrectomy pseudophakic/aphakic status (OR, 2.04; P < 0.001). Decision-tree analysis showed that the stronger predictor of LOH was intraoperative triamcinolone use (P < 0.001). Secondary predictors were a preoperative intraocular pressure more than 15 mmHg (P < 0.001) in eyes that use triamcinolone, and postvitrectomy pseudophakic/aphakic status (P = 0.007) in eyes that did not use triamcinolone. Conclusion: Late-onset ocular hypertension occurred in 4.9% of vitrectomized eyes. The main risk factors were intraoperative use of triamcinolone and postvitrectomy pseudophakic/aphakic status.

Purpose: To assess the effect of topical antibiotic prophylaxis on postoperative endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents.Methods: A systematic literature search was performed from inception to March 2016 using PubMed, Medline, Web of Science, Embase, and the Cochrane Library, to identify articles that reported cases of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents. We used a pooled analysis to estimate the incidence of cases of endophthalmitis who developed after injections performed with and without topical antibiotic prophylaxis. We used regression analysis to explore the effects of study characteristics on heterogeneity.Results: From our search of electronic databases, we identified and screened 4,561 unique records. We judged 60 articles to have reported findings for cohorts of patients who met our inclusion criteria, (12 arms of randomized clinical trials, 11 prospective cohort studies, and 37 retrospective cohort studies), which included 244 cases of endophthalmitis and 639,391 intravitreal injections of anti-vascular endothelial growth factor agents. The final pooled estimate endophthalmitis proportions were 9/10,000 (95% confidence interval, 7/10,000-12/10,000) in the antibiotic-treated group and 3/10,000 (95% confidence interval, 2/10,000-5/10,000) in the untreated group. The estimated incidence of endophthalmitis with topical antibiotic prophylaxis was approximated three times the incidence without prophylaxis. Random effects regression showed that none of the study characteristics significantly affected the effect size in either group.Conclusion: Topical antibiotic after intravitreal injection of anti-vascular endothelial growth factor agents is associated with a higher risk of endophthalmitis.

Purpose. To evaluate the effects of a modification of the traditional 25-gauge pars plana vitrectomy technique in the treatment of uncomplicated macula-on rhegmatogenous retinal detachment (RRD) with intermediate retinal break(s) and marked vitreous traction in the phakic eye. Methods. Prospective, noncomparative, and interventional case series. All consecutive phakic eyes with primary uncomplicated macula-on RRD with intermediate retinal break(s) and marked vitreous traction, with at least 1 year of postoperative follow-up, were enrolled. In all eyes, “localized 25-gauge vitrectomy” under air infusion with localized removal of the vitreous surrounding the retinal break(s), in association with laser photocoagulation and air tamponade, was performed. The primary end point was the rate of primary retinal attachment. Secondary end points were cataract progression and assessed by digital Scheimpflug lens photography (mean change of nuclear density units) and the rate of complications. Results. Thirty-two phakic eyes were included in the final analysis. At 12 months, the primary outcome of anatomical success was achieved in 94% of eyes. The mean nuclear density units did not change significantly at any time point during the follow-up. After localized vitrectomy, one eye developed an epiretinal membrane, and one eye developed cystoid macular edema; no other significant complications were reported. Conclusions. “Localized vitrectomy” has a high anatomical success rate in phakic eyes with primary uncomplicated macula-on RRD with intermediate retinal break(s) and marked vitreous traction, without causing progression of cataract.

Background Internal limiting membrane (ILM) peeling during primary vitrectomy for rhegmatogenous retinal detachment (RRD) prevents the formation of postoperative macular epiretinal membrane (ERM). However, studies that compared vitrectomy with and without ILM peeling for RRD, have reported controversial outcomes. Objective To assess the efficacy of ILM peeling versus non-ILM peeling during vitrectomy for RRD by a systematic review and meta-analysis of published studies. Methods PubMed, Medline, Web of Science, Embase databases, and the Cochrane Library were searched up to April 2018 to identify studies that compared primary vitrectomy with and without ILM peeling for RRD with at least six months follow-up. Primary outcomes were the rate of postoperative ERM formation and mean best corrected visual acuity (BCVA) change after vitrectomy. Rate of recurrence of retinal detachment (RD) was assessed as secondary outcome. Risk ratios (RRs) with 95% confidence intervals (CIs) expressed pooled results for rate of ERM formation and rate of RD recurrence in ILM peeling and non-ILM peeling groups. Pooled results for BCVA change in the two groups were expressed as Weighted Mean Difference (WMD) with 95% CIs. Results Nine studies, one of which was a randomized controlled trial (RCT), with a total number of 404 eyes in the ILM peeling group and 365 eyes in the non-ILM peeling group, were included. The analysis from pooled data indicated a significant lower rate of postoperative ERM formation in the ILM peeling group compared to the non-ILM peeling group (9 studies, 769 eyes, RR = 0.14; CI: 0.07 to 0.28; P < 0.001). There was no statistical difference in mean BCVA change (9 studies, 769 eyes, WMD = 0.02; CI: -0.11 to 0.16; P = 0.75). Rate of recurrence of RD was lower in the ILM peeling group (6 studies, 603 eyes, RR = 0.32; CI = 0.17 to 0.61; P< 0.001). Conclusion ILM peeling during vitrectomy for RRD prevents the formation of macular epiretinal membrane postoperatively and reduces the incidence of RD recurrence, but better visual outcome was not found compared to non-ILM peeling vitrectomy.

Aim The aim of this study is to evaluate long-term efficacy of intravitreal injections of aflibercept as primary treatment for subfoveal/juxtafoveal myopic choroidal neovascularisation (CNV). Methods Thirty-eight treatment-naive eyes of thirty-eight patients with subfoveal/juxtafoveal myopic CNV received initial intravitreal aflibercept injections and were followed for at least 18 months. Aflibercept was applied again for persistent or recurrent CNV, as required. Statistical analysis was carried out using SPSS. Results Mean patient age was 45.8 years, and mean eye refractive error was −7.79 D. For the total patient group (n=38 eyes), mean logMAR best-corrected visual acuity (BCVA) significantly improved from 0.69 at baseline to 0.15 at 18 months (P

Uveal melanoma (UM) represents approximately 5-6% of all melanoma diagnoses and up to 50% of patients succumb to their disease. Although several methods are available, accurate diagnosis is not always easily feasible because of potential accidents (e.g., intraocular hemorrhage). Based on the assumption that the profile of circulating miRNAs is often altered in human cancers, we verified whether UM patients showed different vitreous humor (VH) or serum miRNA profiles with respect to healthy controls. By using TaqMan Low Density Arrays, we analyzed 754 miRNAs from VH, vitreal exosomes, and serum of 6 UM patients and 6 healthy donors: our data demonstrated that the UM VH profile was unique and only partially overlapping with that from serum of the same patients. Whereas, 90% of miRNAs were shared between VH and vitreal exosomes, and their alterations in UM were statistically overlapped with those of VH and vitreal exosomes, suggesting that VH alterations could result from exosomal dysregulation. We report 32 miRNAs differentially expressed in UM patients in at least 2 different types of samples analyzed. We validated these data on an independent cohort of 12 UM patients. Most alterations were common to VH and vitreal exosomes (e.g., upregulation of miR-21,-34 a,-146a). Interestingly, miR-146a was upregulated in the serum of UM patients, as well as in serum exosomes. Upregulation of miR-21 and miR-146a was also detected in formalin-fixed, paraffin-embedded UM, suggesting that VH or serum alterations in UM could be the consequence of disregulation arising from tumoral cells. Our findings suggest the possibility to detect in VH and serum of UM patients "diagnostic" miRNAs released by the affected eye: based on this, miR-146a could be considered a potential circulating marker of UM.

Purpose: To compare the clinical outcomes and the rate of complications of 27-gauge transconjunctival nonvitrectomizing vitreous surgery (NVS) and of 25-gauge transconjunctival sutureless vitrectomy surgery for idiopathic epiretinal membrane removal. Methods: In this prospective randomized study, 83 phakic eyes of 83 consecutive patients with an idiopathic epiretinal membrane were randomized to receive 27-gauge NVS (NVS-group) or 25-gauge vitrectomy (Standard-group). Main outcome measures were best-corrected visual acuity, central retinal thickness, nuclear density units' changes, and rate of complications. Results: Thirty-nine eyes of the Standard-group and 40 of the NVS-group were considered in final analysis. Mean best-corrected visual acuity improved significantly in both groups, with a significant better result at 12 months in NVS-group (P 0.039; t-test). Central retinal thickness decreased significantly in both groups (P < 0.001, Tukey test), without significant difference between the two groups at any time point. At 12 months, nuclear density increased significantly in the Standard-group (analysis of variance, P < 0.001), and it did not change in the NVS-group (analysis of variance, P 0.537). Epiretinal membrane recurred in 5.1% of eyes in the Standard-group and in 7.5% of eyes in the NVS-group (Fisher's exact test, P 1.000). Conclusion: The 27-gauge NVS is an effective surgical procedure in eyes with epiretinal membrane and it induces less progression of nuclear sclerosis than 25-gauge vitrectomy.

Purpose: To evaluate the efficacy and the rate of side effects of the pegylated aptamer pegaptanib in the treatment of patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) and a history of previous arterial thromboembolic events (ATEs). Methods: Twenty-three eyes of 23 patients with subfoveal CNV due to AMD and cerebrovascular accidents (n = 12) and myocardial infarction (n = 11) in the previous 6 months received intravitreal pegaptanib 0.3 mg according to a pro re nata regimen and were followed for 12 months. The paired Student t test was used to evaluate mean changes in best-corrected visual acuity (BCVA; primary outcome measure) and central foveal thickness (CFT). Results: The mean patient age was 71.5 ± 4.6 years; there were 14 women and 9 men. The CNV was type 1, 2, and 3 in 18, 3, and 2 eyes, respectively. The mean BCVA improved from 0.67 ± 0.23 logMAR at baseline to 0.52 ± 0.31 logMAR at the end of 12-month follow-up (p = 0.044). Thirty-five percent of patients achieved ≥3 Early Treatment Diabetic Retinopathy Study lines improvement at 12 months. Mean CFT at baseline (381 ± 111 µm) decreased to 304 ± 82 µm at 12 months (p = 0.008). Patients received a mean of 4.3 ± 1.3 (range 3-7) injections. No systemic or ocular side effects occurred; no patient experienced further ATEs. Conclusions: Intravitreal pegaptanib can be considered a viable treatment option for patients with AMD-related CNV who are at high risk of ATEs.

Purpose: To evaluate the morphology of optic nerve head (ONH) and border tissue (BT) of Elschnig in glaucomatous eyes with visual field defects in superior or inferior hemifield. Methods: In a case-control study, we included 25 patients with superior arcuate scotoma, 25 patients with inferior arcuate scotoma, and 25 healthy controls. They received visual field testing, measurement of peripapillary retinal nerve fiber layer (RNFL) thickness, and ONH examination in a radial pattern with spectral-domain optical coherence tomography. In each ONH scan, the length of Bruch membrane opening (BMO) and BT were measured. Pattern deviation of 6 areas of the visual field and RNFL thickness in corresponding sectors was calculated. Results: Mean BMO length did not differ between groups. Compared with controls, glaucomatous eyes with superior scotoma had a greater BT length in inferior sectors (pConclusions: In patients with arcuate scotoma in one hemifield, the length of the BT correlates with glaucomatous anatomical and functional damage.

Age related macular degeneration (AMD) is the leading cause of blindness among people aged 50 and over. Retinal deposition of amyloid-β (Aβ) aggregates in AMD patients has suggested a potential link between AMD and Alzheimer's disease (AD). We have evaluated the differential retinal expression profile of miRNAs in a rat model of AMD elicited by Aβ. A serum profile of miRNAs in AMD patients has been also assessed using single TaqMan assay. Analysis of retina from rats intravitreally injected with Aβ revealed that miR-27a, miR-146a, and miR-155 were up-regulated in comparison to control rats. Seven miRNA (miR-9, miR-23a, miR-27a, miR-34a, miR-126, miR-146a, and miR-155) have been found to be dysregulated in serum of AMD patients in comparison to control group. Analysis of pathways has revealed that dysregulated miRNAs, both in the AMD animal model and in AMD patients, can target genes regulating pathways linked to neurodegeneration and inflammation, reinforcing the hypothesis that AMD is a protein misfolding disease similar to AD. In fact, miR-9, miR-23a, miR-27a, miR-34a, miR-146a, miR-155 have been found to be dysregulated both in AMD and AD. In conclusion, we suggest that miR-9, miR-23a, miR-27a, miR-34a, miR-146a, miR-155 represent potential biomarkers and new pharmacological targets for AMD.

Purpose The aim of the present study was to assess the expression of miRNAs in the Vitreous Humor (VH) of patients with Macular Hole (MH) and Epiretinal Membrane (ERM) compared to a control group. Methods In this prospective, comparative study, 2-ml of VH was extracted from the core of the vitreous chamber in consecutive patients who underwent standard vitrectomy for ERM and MH. RNA was extracted and TaqMan® Low Density Arrays (TLDAs) were used to profile the transcriptome of 754 miRNAs. Results were validated by single TaqMan® assays. Finally, we created a biological network of differentially expressed miRNA targets and their nearest neighbors. Results Overall 10 eyes with MH, 16 eyes with idiopathic ERM and 6 controls were enrolled in the study. Profiling data identified 5 miRNAs differentially expressed in patients affected by MH and ERM with respect to controls. Four were downregulated (miR-19b, miR-24, miR-155, miR-451) and 1 was downregulated (miR-29a); TaqMan® assays of the VH of patients affected by MH and ERM, with respect to controls, showed that the most differentially expressed were miR-19b (FC -9.13, p: < 0.00004), mir-24 (FC -7.52, p: < 0.004) and miR-142-3p (FC -5.32, p: < 0.011). Our network data showed that deregulation of differentially expressed miRNAs induces an alteration of several pathways associated with genes involved in both MH and ERM. Conclusion The present study suggests that disregulation of miR-19b, miR-24 and miR-142-3p, might be related to the alterations that characterize patients affected by MH and ERM.

PURPOSE To evaluate the efficacy of an intravitreal dexamethasone (Dex) implant 0.7 mg compared with intravitreal ranibizumab (Ra) for the treatment of radiation maculopathy with macular edema secondary to plaque brachytherapy in choroidal melanoma. METHODS Eight patients were treated with intravitreal Ra, and eight patients received the Dex intravitreal implant. Visual acuity and foveal thickness were evaluated using spectral domain optical coherence tomography. RESULTS The mean calculated irradiation to the fovea and mean times from brachytherapy to maculopathy development did not differ significantly between groups. In the Ra group, a mean 7.8 ± 3.9 injections were given and the mean follow-up was 33 ± 15 months (range, 7-52 months). In the Dex group, a mean 2.1 ± 0.8 injections were given and the mean follow-up was 22 ± 7 months (range, 11-31 months). The mean visual acuity improved significantly from the baseline to the last follow-up visit in both groups. Foveal thickness decreased significantly in both groups from 459 ± 81 μm to 243 ± 58 μm and from 437 ± 71 μm to 254 ± 44 μm from the baseline to the last follow-up visit in the Ra and Dex groups, respectively. No patients developed significant cataract or ocular hypertension in both groups. CONCLUSION Both Ra and Dex are effective treatments for macular edema secondary to plaque brachytherapy for uveal melanoma. Dex-treated patients required fewer injections to achieve anatomical and functional improvement.

PURPOSE To compare the changes in postoperative peripapillary retinal nerve fiber layer (p-RNFL) thickness after vitrectomy for epiretinal membrane in eyes with preexisting posterior vitreous detachment (PVD) and eyes with surgically induced PVD. METHODS This study included consecutive patients who underwent 25-gauge vitrectomy for epiretinal membrane. Eyes were divided, according to intraoperative PVD status, into a preexisting PVD group and surgically induced PVD group. Best-corrected visual acuity, p-RNFL thickness, and central retinal thickness were performed before and at 1, 3, and 6 months after surgery. RESULTS One hundred and twenty eyes of 120 patients were enrolled: 64 eyes in the preexisting PVD group and 56 eyes in the surgically induced PVD group. In the preexisting PVD group at 6 months, the mean global p-RNFL thickness did not change, whereas it was reduced in the temporal sector (P = 0.034). In the surgically induced PVD group at 6 months, significant decreases were observed in global p-RNFL thickness (P = 0.027), temporal (P = 0.021), temporal inferior (P = 0.030), and nasal inferior sectors (P = 0.010). At 6 months, the two groups differed significantly in temporal (P < 0.001) and temporal inferior sectors (P = 0.004). The preoperative mean best-corrected visual acuity improved significantly at 6 months in both groups. CONCLUSION Postoperative p-RNFL thickness after vitrectomy for epiretinal membrane tended to decrease in the temporal sector in all eyes and in the temporal inferior and nasal inferior sectors in eyes with surgically induced PVD.

Purpose: The vitreous cortex, epiretinal membrane (ERM), and inner limiting membrane (ILM) are transparent tissues and are thus difficult to visualize. Staining these structures can increase the efficiency of a nontraumatic removal. Methods: The surgeon performs a partial core vitrectomy and induces a posterior vitreous detachment. The vital dye is then injected into the retrohyaloid space in balanced salt solution (BSS). The dyes used are TWIN (Alchimia srl, Padova, Italy), MembraneBlue-Dual (DORC International, Zuidland, the Netherlands), and Doubledyne (Alfa Intes, Casoria, Italy). The surgeon can complete the vitrectomy and gradually aspirate the dye with the probe. Once the vitrectomy is complete, the surgeon can perform the peeling of the ERM without the need to reinject the vital dye over the macula. Results: The presence of the dye over the macula facilitates visualization of the vitreous cortex by blocking the red reflex and increasing the contrast power of the coaxial light probe during the vitrectomy. This allows a negative coloration of the vitreous because the dye acts by increasing the visibility of the surrounding BSS and not the vitreous itself. Conclusions: We describe a new chromovitrectomy technique using the same dye to increase the visualization of the vitreous, posterior hyaloid, ERM, and ILM.

Purpose. To investigate the effectiveness and safety of combined phacoemulsification and dexamethasone intravitreal implant in patients with cataract and diabetic macular edema. Methods. In this two-center, retrospective, single-group study, the charts of 16 consecutive patients who underwent combined phacoemulsification and intravitreal dexamethasone implant were retrospectively reviewed. These 16 patients, 7 men and 9 women, were observed at least 3 months of follow-up. Primary outcome was the change of the central retinal thickness (CRT); secondary outcome was the change of best-corrected visual acuity (BCVA). Any ocular complications were recorded. Results. Mean CRT decreased significantly from 486 ± 152.4 μm at baseline to 365.5 ± 91 μm at 30 days (p=.005), to 326 ± 80 μm at 60 days (p=.0004), and to 362 ± 134 μm at 90 days (p=.001). Mean BCVA was 20/105 (logMAR, 0.72 ± 0.34) at baseline and improved significantly (p≤.007) at all postsurgery time points. One case of ocular hypertension was observed and successfully managed with topical therapy. No endophthalmitis or other ocular complications were observed. Conclusion. Intravitreal slow-release dexamethasone implant combined with cataract surgery may be an effective approach on morphologic and functional outcomes for patients with cataract and diabetic macular edema for at least three months after surgery.

The purpose of this prospective study was to investigate the proton-beam-induced changes in apparent diffusion coefficient (ADC) values of ocular melanoma treated with proton-beam therapy (PBT) in patients undergoing long-term magnetic resonance imaging (MRI) follow-up and to assess whether variations in ADC constitute a reliable biomarker for predicting and detecting the response of ocular melanoma to PBT. Seventeen patients with ocular melanoma treated with PBT were enrolled. All patients underwent conventional MRI and diffusion-weighted imaging (DWI) at baseline and 1, 3, 6, and 18 months after the beginning of therapy. Tumor volumes and ADC values of ocular lesions were measured at each examination. Tumor volumes and mean ADC measurements of the five examination series were compared; correlation of ADC values and tumor regression was estimated. Mean ADC values of ocular melanomas significantly increased already 1 month after therapy whereas tumor volume significantly decreased only 6 months after therapy. Pretreatment ADC value of ocular melanomas and early change in ADC value 1 month after therapy significantly correlated with tumor regression. In ocular melanoma treated with PBT, ADC variations precede volume changes. Both pretreatment ADC and early change in ADC value may predict treatment response, thus expanding the role of DWI from diagnostic to prognostic.

Melanoma of the uveal tract accounts for approximately 5% of all melanomas and represents the most common primary intraocular malignancy. Despite improvements in diagnosis and more effective local therapies for primary cancer, the rate of metastatic death has not changed in the past forty years. In the present study, we made use of bioinformatics to analyze the data obtained from three public available microarray datasets on uveal melanoma in an attempt to identify novel putative chemotherapeutic options for the liver metastatic disease. We have first carried out a meta-analysis of publicly available whole-genome datasets, that included data from 132 patients, comparing metastatic vs. non metastatic uveal melanomas, in order to identify the most relevant genes characterizing the spreading of tumor to the liver. Subsequently, the L1000CDS2 web-based utility was used to predict small molecules and drugs targeting the metastatic uveal melanoma gene signature. The most promising drugs were found to be Cinnarizine, an anti-histaminic drug used for motion sickness, Digitoxigenin, a precursor of cardiac glycosides, and Clofazimine, a fat-soluble iminophenazine used in leprosy. In vitro and in vivo validation studies will be needed to confirm the efficacy of these molecules for the prevention and treatment of metastatic uveal melanoma.

To evaluate the diagnostic efficacy of optical coherence tomography (OCT) angiography, in patients with pre-perimetric open-angle glaucoma. Thirty-eight consecutive eyes of 26 patients with pre-perimetric open-angle glaucoma and 48 normal eyes of 32 controls were included in this prospective study. We evaluated OCT angiography, spectral-domain OCT and visual fields parameters. Differences between controls and patients and between OCT angiography parameters and traditional glaucoma measurements were evaluated. Receiver operating characteristic curves for OCT angiography parameters were assessed. The flow index (p = 0.021) and vessel density (p = 0.001) were significantly lower in pre-perimetric glaucoma eyes versus normal eyes. Ganglion cell complex parameters were significantly correlated to OCT angiography parameters (p

PurposeTo evaluate the morphology of optic nerve head by spectral-domain optical coherence tomography (SD-OCT) in patients with unilateral central retinal vein occlusion (CRVO).MethodsIn 39 consecutive patients with unilateral CRVO and 39 healthy controls, morphologic parameters of optic nerve head were assessed in both eyes by Spectralis SD-OCT using a custom radial B-scan pattern. The length of Bruch membrane opening (BMO) was measured in OCT scans, and optic disc diameters (DD) were assessed in infrared fundus photographs. Axial length was determined by IOLMaster.ResultsThe BMO length was measured in all eyes with CRVO, while DD was not assessed in 9 eyes (27.3%) that had undefined disc margins. Compared to healthy controls (mean BMO length 1,511 ± 79 μm, mean disc diameter 1,521 ± 77 μm), in eyes with CRVO with defined disc margins (n = 28 [71.8%]), no significant difference was found in BMO length and DD (1,473 ± 118 μm and 1,516 ± 104 μm, respectively). Eyes with CRVO with undefined disc margins had lower BMO length (1,289 ± 61 μm [-14.7%], p = 0.001); also, in fellow eyes, these patients had lower BMO length and DD. In all groups, no significant difference was seen between BMO and DD. A correlation was found between axial length and BMO length and disc diameter (both pConclusionsMost of the eyes with CRVO had normal optic disc diameter, but about 25% of patients with CRVO have reduced optic disc dimensions.

To determine the correlation between the area of morphological changes on the macular surface, the depth of intraretinal changes and the best-corrected visual acuity (BCVA) in patients with idiopathic epiretinal membrane. In this prospective cross-sectional study, 38 patients underwent BCVA testing with a Snellen eye chart. The depth of traction, photoreceptor outer segment layer (PROS) thickness, central macular thickness (CMT) and presence of intraretinal cysts were measured using the Avanti RTVue XR and 3D Widefield Enface OCT instruments. Enface sections were performed at the inner limiting membrane (ILM) line level (ILM offset). Patients were categorized into two groups: in group 1 (n = 21), the depth of traction was within 90 μm from the ILM, and in group 2 (n = 17) it was beyond 90 μm from the ILM. The main outcome measure was the correlation between area of epiretinal traction and BCVA according to the depth of traction. In group 1, the depth of traction was 55.15 ± 14.28 μm, the area of traction was 38.95 ± 13.63 mm2, PROS thickness was 51.20 ± 7.23 μm, and CMT was 362.65 ± 41.08 μm. In group 2, the depth of traction was 112.24 ± 10.89 μm, the area of traction was 25.18 ± 4.07 mm2, PROS thickness was 50.24 ± 9.01 μm, and mean CMT was 534.29 ± 126.81 μm. Statistically significant differences in depth of traction, area of traction and CMT were found between the two groups (P

We report an atypical presentation of Antiphospholipid syndrome (APS) with concomitant subhyaloid hemorrhage, engorged and tortuous retinal veins, intraretinal hemorrhages, and cotton wool spots in a 38-year-old female. Medical treatment was preferred to any invasive treatment. The subhyaloid hemorrhage resolved spontaneously and the patient recovered a visual acuity of 20/20 in her right eye 3 months after the initial episode. A prompt diagnosis of this condition is fundamental to consider a systemic treatment to avoid any further thrombosis.

Purpose: To investigate, with spectral-domain optical coherence tomography, if the preoperative status of the retinal pigment epithelium (RPE) affects the postoperative foveal morphology and visual outcomes in eyes with surgically closed macular holes (MHs). Methods: In 52 eyes with surgically closed MHs, preoperative RPE morphology was evaluated and graded based on the measurement of the largest hyperreflective protrusions above the RPE line. Foveal microstructural features and best-corrected visual acuity (BCVA) were evaluated 12 months after surgery. Results: At 12 months, a significant correlation was found between postoperative degree of integrity of the photoreceptors with preoperative RPE morphology, and base diameter of the hole (p = 0.003 and p = 0.028, respectively); mean BCVA at 12 months in eyes with diffuse RPE alteration was significantly lower than in eyes with small or no RPE alteration (p < 0.05). Conclusions: Preoperative RPE integrity may be indicative of good photoreceptor restoration and visual recovery in patients with surgically closed MHs.

The study&rsquo, s purpose was to determine the incidence, risk factors, and outcomes of tractional macular detachment after anti-vascular endothelial growth factor (VEGF) pretreatment before vitrectomy for complicated proliferative diabetic retinopathy. Patients who underwent primary vitrectomy for complicated proliferative diabetic retinopathy, from January 2012 to 31 December 2018, were enrolled. Ophthalmic and pre-operative data were extracted from electronic record systems. All eyes with a valuable Optical Coherence Tomography (OCT)performed within 5 days before injection of anti-VEGF and on the day of vitrectomy were included. Multivariable logistic regression showed that significant risk factors for developing tractional macular detachment included days between anti-VEGF and vitrectomy (OR, 0.71 [95% CI 0.65&ndash, 0.76], p &lt, 0.001), vitreous hemorrhage (OR, 0.23 [95% CI 0.11&ndash, 0.49], 0.001), and age (OR, 1.05 [95% CI 1.02&ndash, 1.08], 0.001). Decision-tree analysis showed that the stronger predictors of tractional macular detachment were the time between anti-VEGF injection and vitrectomy (p &lt, 0.001). Secondary predictors were the presence of vitreous hemorrhage (p = 0.012) in eyes that underwent vitrectomy between 6 and 10 days after anti-VEGF injection and younger age (p = 0.031) in eyes that underwent vitrectomy 10 days after anti-VEGF injection. Tractional macular detachment occurs in 10% of eyes after anti-VEGF injection, the main risk factors being days between anti-VEGF injection and vitrectomy, vitreous hemorrhage, and age.

In order to investigate Insulin-like growth factor-1 (IGF-1) blood levels in male and female age-matched patients affected by early, intermediate, neovascular age related macular degeneration (AMD) and healthy subjects (no AMD) were enrolled in a prospective, observational study. All patients enrolled were classified according to 4 stages classification of AMD from Age-related eye disease study (AREDS). Each subject underwent a complete ophthalmic examination including best corrected visual acuity (BCVA), applanation tonometry, slit-lamp biomicroscopic examination, color fundus photography, optical coherence tomography (OCT) and, if needed, fluorescein angiography. Overall, 224 anti-VEGF naïve subjects including 56 patients in early AMD group, 56 patients in intermediate AMD group, 56 patients in neovascular AMD group and 56 patients in no AMD group were recruited. For each group 28 male patients and 28 female patients were enrolled. IGF-1 hematic levels were significantly higher (p0.005) in the neovascular AMD group and in the intermediate AMD group in comparison to no AMD group; no significant difference between early AMD group and no AMD group was found. Our analysis has shown an increment of IGF-1 levels in both neovascular and intermediate stage of AMD supporting the hypothesis that IGF-1 may play a role in the pathogenesis of AMD.

Previous studies proposed the application of DNA methylation signatures as clinical biomarkers of age-related macular degeneration (AMD). However, the characterization of Long Interspersed Nuclear Element-1 (LINE-1) methylation levels—a surrogate marker of global DNA methylation—in AMD patients has not been investigated so far. In the present study, we first characterized DNA methyltransferases (DNMTs) and Sirtuin 1 (SIRT1) functions in blood samples of 40 AMD patients and 10 age- and sex-matched controls. Then, we evaluated whether changes in DNMTs functions were associated with different LINE-1 methylation levels in leukocyte DNA. We demonstrated that total DNMTs activity was 48% higher in AMD patients than in controls (p = 0.005). AMD patients also exhibited up-regulation of DNMT1 and DNMT3B expression (FC = 2.6; p = 0.003 and FC = 2.4; p = 0.018, respectively). In line with increased DNMTs functions, the LINE-1 methylation level was higher in AMD patients than in controls (mean = 69.10%; SE = 0.68 vs. mean = 65.73%; SE = 0.59; p = 0.020). All p-values were adjusted by Bonferroni correction. In AMD patients, LINE-1 methylation level was positively associated with total DNMTs activity (r = 0.694; p < 0.001), DNMT1 (r = 0.579; p < 0.001), and DNMT3B (r = 0.521; p = 0.001) expression. Our results encourage further large-size prospective research to understand the relationship between LINE-1 methylation and AMD aetiology, and its usefulness in the clinical setting.

PURPOSE: To evaluate the demographic, geographic, and race-related variables that account for geographic variability in prevalence rates of age-related macular degeneration (AMD). DESIGN: Systematic review, meta-regression, and decision-tree analysis. METHODS: A systematic literature review of PubMed, Medline, Web of Science, and Embase databases identified population-based studies on the prevalence of AMD published before May 2014. Only population-based studies that took place in a spatially explicit geographic area that could be geolocalized, and used retinal photographs and standardized grading classifications, were included. Latitude and longitude data (geolocalization) and the mean annual insolation for the area where survey took place were obtained. Age-standardized prevalence rates across studies were estimated using the direct standardization method. Correlations between the prevalence of AMD and longitude and latitude were obtained by regression analysis. A hierarchical Bayesian meta-regression approach was used to assess the association between the prevalence of AMD and other relevant factors. We further investigated the interplay between location and these factors on the prevalence of AMD using regression based on conditional-inference decision trees. RESULTS: We observed significant inverse correlations between latitude or longitude, and crude or age-standardized prevalence rates, of early and late AMD (P < .001). Metaregression analysis showed that insolation, latitude, longitude, age, and race have a significant effect on the prevalence rates of early and late AMD (P < .001). Decision-tree analysis identified that the most important predictive variable was race for early AMD (P = .002) and insolation for late AMD (P = .001). CONCLUSIONS: Geographic position and insolation are key factors in the prevalence of AMD.

Purpose The aim of this study was to compare the efficiency and safety of ultrahigh-speed cut rate 25-gauge system and standard cut rate 25-gauge vitrectomy system. Methods In this single-center, prospective randomized study, all consecutive eyes that underwent 25-gauge vitrectomy at the Eye Clinic of the University of Ancona from September 2014 to November 2014 were randomized to receive 25-gauge vitrectomy with 7,500 cuts per minute (cpm) probes (7,500 Group) or 25-gauge vitrectomy with 5,000 cpm probes (Standard Group). Exclusion criteria were previously vitrectomized eye, trauma cases, retinal detachment with proliferative vitreoretinopathy, and endophthalmitis. Main outcome measure was core vitrectomy duration. Secondary outcome was the incidence of iatrogenic retinal breaks and other complications related to surgery. Results Overall, 62 eyes were enrolled; 31 eyes received 25-gauge 7,500 cpm vitrectomy and 31 eyes received 25-gauge 5,000 cpm vitrectomy. The duration of core vitrectomy was significantly lower in the 7,500 Group (P = 0.030, t-test for independent samples). Mean ± standard deviation core vitrectomy time was 161.32 ± 39.10 seconds in the 7,500 Group and 184.10 ± 41.69 seconds in the Standard Group. The observed difference in mean core vitrectomy duration between subjects treated with 7,500 cpm probes and those in the Standard Group was equal -22 seconds (95% confidence interval: -43.3 to -2.2). There was no difference in the incidence of iatrogenic breaks between the 2 groups, and there were no other complications over a 3-month follow-up period. Conclusion The 25-gauge 7,500 cpm vitrectomy is an effective and safe surgical procedure, and it can significantly reduce core vitrectomy time in eyes undergoing vitreoretinal surgery.

We evaluated spectral-domain optical coherence tomography (SD-OCT) parameters and visual field parameters in patients with different degrees of open-angle glaucoma (preperimetric, mild, moderate, and severe glaucoma) to determine which parameter best identifies each glaucomatous group.A total of 131 patients (66 preperimetric, 41 mild, 35 moderate, 40 severe glaucomatous eyes) and 40 normal eyes (control group) were included in this prospective study. The SD-OCT parameters [mean ganglion cell complex (GCC), superior GCC, inferior GCC, global loss volume, focal loss volume, mean circumpapillary retinal nerve fiber layer (RNFL), superior circumpapillary retinal nerve fiber layer [cpRNFL], and inferior cpRNFL] and visual field parameters (mean deviation and pattern SD) were evaluated. The area under the receiver operating characteristic curve (AUROC) was calculated for each parameter to determine which best identified glaucomatous changes.Of the SD-OCT parameters, inferior (AUROC, 0.792) and mean GCC thickness (AUROC, 0.741) best discriminated between normal eyes and preperimetric glaucoma eyes.GCC measurements were more efficient than cpRNFL measurements in detecting preperimetric glaucomatous damage. This finding could be an aid to an early diagnosis.

An 83-year-old pseudophakic woman fell and sustained an open-globe injury to her left eye with traumatic aniridia, aphakia, and a total retinal detachment. Visual acuity was light perception. After primary repair of the ruptured globe, the retina was reattached using silicone oil tamponade with placement of silicone oil retention sutures to prevent the oil from touching the corneal endothelium. Three months later, the oil was removed and with glare, aphakic correction improved the patient's visual acuity to 20/80 −1 . A scleral-fixated artificial iris–intraocular lens (IOL) was subsequently implanted. During placement of the IOL through a temporal corneoscleral beveled incision into the anterior chamber, the silicone oil retention sutures supported the optic as it was scleral fixated. The retention sutures aided in the placement of the IOL and prevented it from subluxating and/or dislocating during surgery. Postoperatively, the corrected visual acuity was 20/50 −2 . Financial Disclosure Dr. Rosenthal is a consultant to and clinical investigator for Ophtec USA, Inc. No other author has a financial or proprietary interest in any material or method mentioned.

To evaluate the transient pattern electroretinogram (t-PERG) and the retinal nerve fiber layer (RNFL) thickness in eyes with ocular hypertension (OH) and normal short-wavelength automated perimetry (SWAP). In 26 patients with bilateral OH with normal SWAP, and in 26 age and sex matched healthy controls, t-PERG recording and RNFL thickness measurement were performed. Mean deviation (MD) and pattern standard deviation (PSD) of a reliable full threshold 24-2 SWAP were considered. RNFL thickness was determined by OCT3. Monocular PERG were recorded by using a black and white checkerboard pattern (check size 0.9°, contrast 100 %, mean luminance 80 cd/m2) generated on a monitor and reversed in contrast (four reversals per second, 2 Hz) at a distance of 70 cm. Patients had optimal correction at viewing distance; no mydriatic or miotic eye drops were used. Silver/silver chloride skin electrodes were placed over the lower eyelids in the stimulated eye (active electrode) and in the patched eye (reference electrode); ground electrode was in the Fpz scalp. Peak-to peak amplitude of P50 (N35-P50) and N95 (P50-N95) waves, and implicit time of P50, were considered. Compared to controls, in OH eyes, a reduction of N35-P50 amplitude (2.86 ± 1.49 vs. 3.77 ± 1.08 microvolts, −24.1 %, t-test p = 0.015), of average RNFL thickness (88 ± 11 vs. 96 ± 10 μm, −9.5 %, t-test p = 0.002), and of RNFL thickness in superior (p = 0.015) and inferior quadrant (p