Increasing incidence of contact-lens-related Acanthamoeba keratitis in a tertiary ophthalmology department in an Italian population.

PURPOSE: The purpose of this paper is to report the increasing incidence of contact-lens related Acanthamoeba keratitis (AK) in a tertiary ophthalmology department in Umbria, central Italy. METHODS: Observational and retrospective case series were carried out. A total of nine eyes with a diagnosis of AK were examined. All patients underwent a full slit lamp examination, in vivo confocal microscopy (IVCM) and corneal scraping. The IVCM was repeated at one and two-week and at one, three and six-month intervals. Samples of domestic tap water were also examined for PCR analysis. Patients were treated with levofloxacin0,5%, Polyhexamethylene biguanide 0.02%, and Propamidine Isetionate0,1%. RESULTS: All patients were contact lens wearers. The average patient age was 27.75 (range 18-45), with three men and five women. The main clinical features were ciliary congestion, diffuse epitheliopathy with punctuated keratitis, multiple, small sub-epithelial, greyish, corneal infiltrates with epithelial defect, pseudodendritic corneal lesions, perineural infiltrates, corneal stromal cellularity, and stromal infiltrates. IVCM was indicative of Acanthamoeba in seven out of the nine eyes. All the positive IVCM images were section images showing double walled, bright-spot cysts with a clear chain-like arrangement of five or more cysts identified in three of the patients. PCR analysis of the water was negative in all cases. CONCLUSION: Although PCR is the most common method used, the increased incidence of AK could mainly be related to a proper IVCM interpretation. A broad-spectrum antibiotic, such as levofloxacin might play a role in the early treatment of AK reducing the virulence of the amoeba.

Bilateral evolution of OCT biomarkers in dry AMD: Long-term follow up study.

PURPOSE: To report the emergence and progress of four late-stage characteristics: incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) and complete RPE and outer retinal atrophy (cRORA), drusen ooze and drusen collapse in eyes with dry age-related macular degeneration (AMD) using Spectral Domain Optical Coherence Tomography (SD-OCT). METHODS: This was a retrospective analysis of eyes with non-exudative AMD. Multimodal imaging was done at follow up visits ≤ 12 months. OCT volume scan was used to assess and identify the 4 characteristics. Univariate analysis was done for the various demographic and clinical characteristics.Patients with a mean age of 76.7 ± 10 years were followed up for 69.9 ± 20.6 months. iRORA, cRORA, drusen ooze was present in 15.6%, 15.6% and 15.6% of patients at baseline, respectively, and 25.0%, 40.6% and 53.1% of patients at the final follow-up, respectively. At baseline 9.1%, 0% and 9.1% of patients had bilateral drusen ooze, iRORA and cRORA, respectively. By the final follow-up, drusen collapse occurred in 46.9% and 18.8% patients in unilateral and bilateral eyes, respectively.For bilateral cases, the mean interval of time between emergence inthe two eyes for drusen ooze, drusen collapse, iRORA, and cRORA was 5 ± 1.4 years, 2.2 ± 2.2 years, 3.5 ± 0.7 and 1.7 ± 0.6 years, respectively. CONCLUSIONS: Late-stage OCT biomarkers are seen bilaterally at 21.9% at baseline and at 56.3% at 5.8 years follow-up. Once present in one eye, cRORA had the shortest mean interval before appearance in the other eye.

Ocular-Surface Regeneration Therapies for Eye Disorders: The State of the Art.

The ocular surface is a complex structure that includes cornea, conjunctiva, limbus, and tear film, and is critical for maintaining visual function. When the ocular-surface integrity is altered by a disease, conventional therapies usually rely on topical drops or tissue replacement with more invasive procedures, such as corneal transplants. However, in the last years, regeneration therapies have emerged as a promising approach to repair the damaged ocular surface by stimulating cell proliferation and restoring the eye homeostasis and function. This article reviews the different strategies employed in ocular-surface regeneration, including cell-based therapies, growth-factor-based therapies, and tissue-engineering approaches. Dry eye and neurotrophic keratopathy diseases can be treated with nerve-growth factors to stimulate the limbal stem-cell proliferation and the corneal nerve regeneration, whereas conjunctival autograft or amniotic membrane are used in subjects with corneal limbus dysfunction, such as limbal stem-cell deficiency or pterygium. Further, new therapies are available for patients with corneal endothelium diseases to promote the expansion and migration of cells without the need of corneal keratoplasty. Finally, gene therapy is a promising new frontier of regeneration medicine that can modify the gene expression and, potentially, restore the corneal transparency by reducing fibrosis and neovascularization, as well as by stimulating stem-cell proliferation and tissue regeneration.

Evaluation of warm compresses and topical cyclosporine treatment in meibomian gland dysfunction by confocal scanning laser microscopy.

PURPOSE: The aim of our study is to confirm the utility of warm compresses (WC) and artificial tears (AT) in meibomian gland dysfunction (MGD) management and to understand if its association with topical cyclosporine A (CsA) improves outcomes. METHODS: Patients with diagnosis of MGD-related dry eye were evaluated. In this prospective, randomized, double-masked study, patients were randomized in two treatments: AT plus WC (group A), and AT plus WC plus CsA 0.05% ophthalmic emulsion (group B). At baseline and at 1, 3, and 6 months, Ocular Surface Disease Index (OSDI) questionnaire was completed, and tear evaluation (BUT, Schirmer and osmolarity test), ocular surface evaluation (fluorescein and lissamine green staining), clinical (Shimazaki grading) and in vivo confocal microscopy (IVCM) evaluation of rete ridges (RRs) were performed. RESULTS: A total of 40 eyes, 20 in each group, completed the study. Analysis of OSDI, tear test, ocular surface evaluation and clinical grading of MG showed significant improvement at 6 months, whereas no difference was found between the two groups at 6 months. The analysis of IVCM showed significant improvement in both groups, but significantly better results in group B were found compared to group A at 6 months. CONCLUSION: WC performed 3 times daily during the 1st month and once daily afterwards, in addition to AT, were useful to manage the obstruction of MG and related signs and symptoms. Additional effects of CsA were visible in IVCM only at 6 months. IVCM is an effective tool to monitor treatments in MGD.

Primary small gauge pars plana vitrectomy and silicone oil endotamponade for endophthalmitis after cataract surgery: Clinical and OCT findings.

BACKGROUND: Retrospective analysis of morphological and functional outcomes after pars-plana vitrectomy and Silicone-Oil (SO) endotamponade in acute postoperative endophthalmitis (APOE). METHODS: Minimum follow-up was 6 months. Every included patient received best-corrected visual acuity (BCVA) assessment, pre-operatively and at last follow-up. Spectralis OCT was used to investigate disorganization of inner (DRIL) and outer (DROL) retinal layers at 1, 3, 6 months and at last follow-up. OCT-A was performed to assess foveal avascular zone (FAZ) and vascular perfusion density (VPD) at 6 months and at last follow-up. RESULTS: Seventeen eyes were recruited. Postoperative findings: BCVA ≥ 20/40 (in 14 eyes); epiretinal membranes (13); hyperreflective epiretinal material soon after surgery in (6) SO-filled eyes; inner retinal layers atrophy (5); macular edema (2); DROL (4) with persistent EZ disruption at final visit (2); no significant difference between study and fellow eyes in central macular thickness, FAZ and VPD; VPD decreased in all cases with prominent disorganization of retinal architecture. CONCLUSION: OCT changes after APOE can be persistent or completely/partially self-resolving and seems related to the outward progression path of the infection/inflammation from the vitreous cavity to the inner and outer retina, rather than to the surgery.

Vitamin B12 levels in patients with retinal vein occlusion and their relation with clinical outcome: a retrospective study.

Retinal vein occlusion (RVO) is the second most common retinal vascular disorder, after diabetic retinopathy. Most patients suffering RVO develop some degree of visual loss consequent to retinal complications such as edema and microhemorrhages. Even if some risk factors for RVO have been identified, the clinical outcome of RVO remains highly unpredictable because studies investigating potential prognostic markers for visual improvement are lacking. Cyanocobalamin belongs to the group of B vitamins and plays a role in homocysteine metabolism; however, cyanocobalamin deficiency associates with an increase of some toxic bioproducts involved in endothelial injury and platelet activation independent of homocysteine levels. We retrospectively evaluated the levels of vitamin B12 at diagnosis in 203 patients with RVO, and in a parallel cohort of 120 age- and sex-matched patients without RVO from an internal medicine ward, and correlated them with visual outcome at follow-up (median time 150 days, IQR 30-210). In patients with RVO, vitamin B12 levels at diagnosis were significantly lower than in controls and independently predicted worse clinical outcome at multivariate analysis (OR 3.2; CIs 1.2-8.2; p = 0.015). Our data suggest the opportunity to prospectively evaluate the effect on visual outcome of cyanocobalamin supplementation in RVO patients.

Optical coherence tomography predictors of progression of non-exudative age-related macular degeneration to advanced atrophic and exudative disease.

PURPOSE: To study the natural history of optical coherence tomography (OCT) imaging-based findings seen in non-exudative age-related macular degeneration (neAMD) and model their relative likelihood in predicting development of incomplete retinal pigment epithelium and outer retinal atrophy (iRORA), complete retinal pigment epithelium and outer retinal atrophy (cRORA), and neovascular AMD (nAMD). METHODS: Retrospective chart review was performed at two academic practices. Patients diagnosed with neAMD for whom yearly OCT scans were obtained for at least 4 consecutive years were included. Baseline demographic, visual acuity, AREDS staging, and OCT data were collected. OCTs were assessed for the presence or absence of eleven features previously individually associated with progression of neAMD, both at baseline, and on all subsequent follow-up scans. Likewise, charts were reviewed to assess visual acuity and staging of NEAMD at all follow-up visits. A multivariate regression analysis was constructed to determine predictors of iRORA, cRORA, and nAMD. RESULTS: A total of 107 eyes of 88 patients were evaluated. Follow-up included yearly OCTs obtained over at least 4 consecutive years follow-up (range: 50-94 months). During the follow-up period, 17 eyes progressed to iRORA while 25 progressed to cRORA and 16 underwent conversion to nAMD. Predictors of conversion to iRORA and cRORA included integrity of the external limiting membrane (p = 0.02), the ellipsoid zone (p = 0.01), and the cone outer segment line (p = 0.003) and the presence of intraretinal hyporeflective spaces (p = 0.009), drusen ooze (p = 0.05), and drusen collapse (p = 0.001). OCT features predictive of conversion to nAMD included outer nuclear layer (ONL) loss (p = 0.01), presence of intraretinal (p = 0.001) and subretinal (p = 0.005) hyporeflective spaces, and drusen collapse (p = 0.003). CONCLUSION: Of these multiple factors predictive of progression of neAMD, the OCT feature most strongly correlated to progression to iRORA/cRORA was drusen collapse, and the feature most predictive of conversion to nAMD was the presence of intraretinal hyporeflective spaces.

Intraretinal, sub-retinal, and sub-retinal pigmented epithelium fluid in non-exudative age-related macular degeneration: follow-up with OCT imaging.

BACKGROUND/OBJECTIVES: To evaluate the presence and evolution of fluid in non-exudative age-related macular degeneration (AMD) through serial OCT. SUBJECTS/METHODS: A retrospective analysis of eyes with non-exudative AMD with a minimum of 4 year follow-up was done. Parameters including intraretinal fluid (IRF), subretinal fluid (SRF), and sub-retinal pigment epithelium (RPE) fluid (SRPEF); subfoveal choroidal thickness (SFCT) and type of drusen were evaluated using optical coherence tomography (OCT) scans at baseline and follow up visits. RESULTS: Seventy-two eyes (in 63 patients) were followed up for an average of 5.83 ± 2.17 years. A total of 26/72 (36%) and 29/65 (52%) of the non-exudative eyes had fluid during baseline and the last visit. Seven eyes (10%) out of 72 eyes converted into exudative AMD or neo-vascular AMD (nAMD) during the study period. SRPEF at baseline was most common fluid location for non-exudative eyes that eventually converted to nAMD. CONCLUSION: Non-exudative fluid including IRF, SRF, and SRPEF is seen in patients with non-exudative AMD with increasing incidence during long term follow-up.

Computational Study of Potential Galectin-3 Inhibitors in the Treatment of COVID-19.

Galectin-3 is a carbohydrate-binding protein and the most studied member of the galectin family. It regulates several functions throughout the body, among which are inflammation and post-injury remodelling. Recent studies have highlighted the similarity between Galectin-3's carbohydrate recognition domain and the so-called "galectin fold" present on the N-terminal domain of the S1 sub-unit of the SARS-CoV-2 spike protein. Sialic acids binding to the N-terminal domain of the Spike protein are known to be crucial for viral entry into humans, and the role of Galectin-3 as a mediator of lung fibrosis has long been the object of study since its levels have been found to be abnormally high in alveolar macrophages following lung injury. In this context, the discovery of a double inhibitor may both prevent viral entry and reduce post-infection pulmonary fibrosis. In this study, we use a database of 56 compounds, among which 37 have known experimental affinity with Galectin-3. We carry out virtual screening of this database with respect to Galectin-3 and Spike protein. Several ligands are found to exhibit promising binding affinity and interaction with the Spike protein's N-terminal domain as well as with Galectin-3. This finding strongly suggests that existing Galectin-3 inhibitors possess dual-binding capabilities to disrupt Spike-ACE2 interactions. Herein we identify the most promising inhibitors of Galectin-3 and Spike proteins, of which five emerge as potential dual effective inhibitors. Our preliminary results warrant further in vitro and in vivo testing of these putative inhibitors against SARS-CoV-2 with the hope of being able to halt the spread of the virus in the future.

Drusen ooze: Predictor for progression of dry age-related macular degeneration.

BACKGROUND: To evaluate natural history of drusen ooze and its role as a predictor for progression of dry age-related macular degeneration (AMD) longitudinally. METHODS: Multi-centric retrospective observational case series of 72 eyes (72 patients) with dry AMD with a minimum follow-up of 4 years. Drusen types were identified on volume scans on optical coherence tomography (OCT) and were characterized for occurrence of drusen ooze at baseline until last visit. Drusen ooze was defined as hyperreflective dots overlying a collapsing drusen or pseudodrusen, or hyperreflective RPE above drusen or isoreflective dots at the level of outer nuclear layer. The consequent incidence of incomplete retinal pigment epithelium and outer retinal atrophy (iRORA), complete retinal pigment epithelium and outer retinal atrophy (cRORA), and neovascular AMD (nAMD) were evaluated statistically. RESULTS: In total, 72 eyes with a mean follow-up of 68.89 (± 25.57 months) were studied. At presentation, 11 eyes (15.3%) had a single drusen type, whereas 61 eyes (84.7%) had mixed drusen. Reticular pseudodrusen were most common (84.7%) followed by soft drusen (66.6%). Drusen ooze was seen in 47 eyes (65.2%) at presentation. The presence of drusen ooze at baseline (p < 0.01) and baseline best corrected visual acuity (BCVA) (p = 0.04) significantly correlated with development of iRORA and cRORA. In total, 14 eyes progressed from iRORA to cRORA over a mean follow up of 29.14 (± 24.33) months. Odds of progression to iRORA or cRORA were 20.3 times greater for eyes with drusen ooze at baseline (95% C.I., 4.4-94.2). CONCLUSIONS: In dry AMD, drusen ooze is a useful sign for predicting progression to iRORA and cRORA over time.