Francesco Boscia

Intravitreal Steroids for the Treatment of Retinal Diseases

Diabetic macular edema (DME), pseudophakic cystoid macular edema (CME), age-related macular degeneration (AMD), retinal vascular occlusion (RVO), and uveitis are ocular conditions related to severe visual impairment worldwide. Corticosteroids have been widely used in the treatment of these retinal diseases, due to their well-known antiangiogenic, antiedematous, and anti-inflammatory properties. Intravitreal steroids have emerged as novel and essential tools in the ophthalmologists armamentarium, allowing for maximization of drug efficacy and limited risk of systemic side effects. Recent advances in ocular drug delivery methods led to the development of intraocular implants, which help to provide prolonged treatment with controlled drug release. Moreover, they may add some potential advantages over traditional intraocular injections by delivering certain rates of drug directly to the site of action, amplifying the drugs half-life, contributing in the minimization of peak plasma levels of the drug, and avoiding the side effects associated with repeated intravitreal injections. The purpose of this review is to provide an update on the use of intravitreal steroids as a treatment option for a variety of retinal diseases and to review the current literature considering their properties, safety, and adverse events.

Ranibizumab in retinal vein occlusion: treatment recommendations by an expert panel

Retinal vein occlusion (RVO) is a common cause of retinal vascular disease, resulting in potentially irreversible loss of vision despite the existence of several therapeutic options. The humanised monoclonal antibody fragment ranibizumab binds to and inhibits vascular endothelial growth factor, a key driver of macular oedema in RVO. In 2010, ranibizumab was approved in the USA for the treatment of macular oedema in RVO and, in 2011, ranibizumab was approved in the European Union for the treatment of visual impairment caused by macular oedema secondary to RVO in branch and central RVO. Ranibizumab provides an additional therapeutic option for this complex disease: an option that was not fully considered during the preparation of current international guidelines. An expert panel was convened to critically evaluate the evidence for treatment with ranibizumab in patients with visual impairment caused by macular oedema secondary to RVO and to develop treatment recommendations, with the aim of assisting physicians to optimise patient treatment.

Dexamethasone implant with fixed or individualized regimen in the treatment of diabetic macular oedema: six‐month outcomes of the UDBASA study

To evaluate a pro re nata administration of Ozurdex® implant versus a single administration for treating diabetic macular oedema (DME).

Plasmapheresis, intravenous immunoglobulins, and autologous serum eyedrops in the acute eye complications of toxic epidermal necrolysis

Purpose Toxic epidermal necrolysis (TEN) is a rare, life-threatening, drug-induced, mucocutaneous disease, which can severely affect the ocular surface. The purpose of this study was to investigate the efficacy of plasmapheresis, human IV immunoglobulins (IVIg), and autologous serum (AS) eyedrops in the treatment of the severe acute ocular complications of TEN. Methods A retrospective chart review of all patients admitted to the Burn Unit, Azienda Ospedaliero-Universitaria-Sassari, Sassari, Italy, from 2009 to 2015, identified 9 patients (2 men, 7 women; mean age 63.8 ± 24.7 years) with TEN. Bilateral, acute ocular surface complications were observed in 7 (78%) patients; 3 showed catarrhal conjunctivitis, whereas 4 had severe pseudomembranous conjunctivitis and corneal ulcers. Results All patients with TEN were immediately treated with plasmapheresis and human IVIg, which produced a marked improvement in the patients’ general condition. In the 3 with catarrhal conjunctivitis, preservative-free artificial tears and topical antibiotics were beneficial. In the 4 with severe pseudomembranous conjunctivitis and corneal ulcers, treatment with AS eyedrops resulted in corneal and conjunctival epithelium healing over 3-6 weeks. After a minimum follow-up of at least 12 months, there were minimal/mild residual signs and symptoms of dry eye. Conclusions Plasmapheresis and IVIg may be life-saving and contribute to reduce ocular surface inflammation in TEN. Autologous serum eyedrops, prepared after plasmapheresis completion and IVIg infusion, may be helpful in the management of the severe acute ocular complications of TEN.

Free-living Amoebae Keratitis

Purpose: To describe the diagnostic and clinical features and treatment results in 43 consecutive patients with microbiologically proven free-living amoebae (FLA) keratitis. Methods: In this hospital-based, prospective case series, corneal scrapings from 43 patients with presumed amoebic keratitis were plated on nonnutrient agar. Amoebic isolates were identified morphologically and by the polymerase chain reaction. All patients with culture-proven FLA keratitis were treated with polyhexamethylene biguanide (PHMB) 0.02% eye drops. Results: Forty-three corneal scrapings from 43 patients were found to be culture positive for FLA; 41 (95%) were from contact lens wearers and 2 (5%) were from noncontact lens wearers. Microscopic examination identified 4 Acanthamoeba spp, 24 Hartmannella spp, 12 vahlkampfiid amoebae, and 3 mixed infections with Hartmannella/vahlkampfiid amoebae. Morphological results were confirmed by the polymerase chain reaction. Patients with Acanthamoeba, Hartmannella, and vahlkampfiid keratitis had indistinguishable clinical features. In 38 eyes with keratitis at an early stage, treatment with PHMB 0.02% eye drops was fully successful. In 5 patients with advanced keratitis, topical PHMB 0.02% controlled the infection, but all of them developed a central corneal scar with visual deterioration. Conclusions: Acanthamoeba is not the only cause of amoebic keratitis, because this condition may also be caused by other FLA, such as Hartmannella and vahlkampfiid amoebae. This finding is epidemiologically interesting, suggesting a possible different geographical prevalence of the different FLA responsible for keratitis. Early diagnosis and proper antiamoebic treatment are crucial to yielding a cure.

Homocysteine and risk of age-related macular degeneration: a systematic review and meta-analysis.

There is still no agreement on total plasma homocysteine (tHcy) role in age‐related macular degeneration (AMD), the leading cause of new blindness in industrialized countries. We performed a systematic review and meta‐analysis of the published data on the correlation between tHcy and AMD. MEDLINE/PubMed and ISI Web of Sciences searches were performed according to MOOSE guidelines. Case–control studies were eligible for inclusion. Participants and controls were AMD patients and subjects without AMD. The main outcome measure was wet AMD. Homocysteine level was the main exposure variable. Data were pooled using a random‐effects model. Twelve case–control studies were identified: 10 assessed wet AMD, four dry AMD, one early AMD, one late AMD, and one any AMD. As for wet AMD, there was a total of 453 cases and 514 controls. Mean tHcy was on average 1.1 μmol/l (95% confidence interval [CI] = 0.96–1.25) greater in wet AMD cases, but there was evidence of extreme between‐study heterogeneity (p < 0.001, I2 = 91.8%). In a model homogenous for age, including six wet AMD studies (214 cases, 274 controls), mean tHcy was on average 0.58 μmol/l (95% CI = 0.35–0.73) greater in the case group, a not statistically significant result (p = 0.144) associated with moderate heterogeneity (I2 = 39.2%). Our meta‐analysis indicates that there is some weak evidence that increased tHcy might be associated with wet AMD; however, this result should be interpreted cautiously, because of a marked between‐study heterogeneity and the possible effect of publication bias. Future studies, preferably of cohort design, are necessary before any firm conclusions on the putative role of increased tHcy on AMD can be drawn.

Aflibercept in the treatment of diabetic macular edema: A review and consensus paper

Purpose To reach a consensus, among experts, on the role of aflibercept in diabetic macular edema (DME) through literature review. Methods Two round tables, involving 12 Italian experts, were organized: in the first one, 6 pharmacologic and clinical questions were selected and analyzed by a systematic literature review, using a population, intervention, control, and outcomes framework; in the second one, the nominal group technique was used to discuss relevant evidence related to each question. The consensus was assessed using the 5-point Delphi score. Results Agreement on statements was reached on 6/6 questions. The final statements were as follows: 1) High levels of both vascular endothelial growth factor (VEGF) and placental growth factor play an important role in the pathogenesis of DME. 2) The aflibercept pharmacologic profile is notably different from that of other anti-VEGF. 3) Aflibercept significantly improves functional and anatomical outcomes, and rapidly improves best-corrected visual acuity up to its peak; these results remain stable over time. 4) Diabetic macular edema aflibercept treatment requires a 5-monthly injection loading phase. Alternatively, a personalized pro re nata (PRN) regimen based on monthly monitoring and strict retreatment criteria can be used. 5) As an alternative to the bimonthly fixed regimen, in the maintenance phase the treatment schedule may be a PRN regimen with strict retreatment criteria or a treat and extend regimen. 6) No concerns on aflibercept ocular and systemic safety emerged from the literature. Conclusions Consensus was reached among experts on how to best treat patients with DME with aflibercept.

Complete Blood Cell Count–Derived Inflammation Biomarkers in Men with Age-Related Macular Degeneration

ABSTRACT Purpose: To investigate the role of some blood count–derived inflammation biomarkers in age-related macular degeneration (AMD). Methods: Seventy-nine men with late-stage AMD and 79 male age-matched cataract controls without AMD were recruited in March–December, 2016. A blood sample was taken. The following blood cell count–derived indexes were evaluated: neutrophil/lymphocyte ratio (NLR), derived NLR [dNLR = neutrophils/(white blood cells ‒ neutrophils)], platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), (neutrophils × monocytes)/lymphocyte ratio (SIRI), and (neutrophils × monocytes × platelets)/lymphocyte ratio (AISI). Results: AMD patients had significantly lower median values of white blood cells, monocytes, neutrophils, platelets, and mean platelet volume (MPV). Regarding the combined indexes, only AISI was significantly lower in AMD patients than in controls. Receiver operating characteristics curve analysis revealed that the ability of AISI and MPV to predict AMD is poor. Conclusion: Results suggests that NLR, dNLR, PLR, MLR, SIRI, and AISI are unreliable disease biomarkers in men with AMD. Larger scale studies are necessary to confirm these findings.

Intravitreal Dexamethasone in Patients with Wet Age-Related Macular Degeneration Resistant to Anti-VEGF: A Prospective Pilot Study

Purpose To evaluate the efficacy and safety of a single intravitreal dexamethasone implant (DXI) combined with intravitreal antivascular endothelial growth factor (anti-VEGF) therapy, in patients with neovascular age-related macular degeneration (wet-AMD) resistant to conventional treatment. Methods In this randomized, controlled pilot study, 16 eyes of 15 patients, unresponsive to anti-VEGF therapy, were enrolled and randomly assigned to two groups: DXI + anti-VEGF (treatment group: 11 eyes) and monthly anti-VEGF alone (control group: 5 eyes). Patients were treated at baseline and followed for 6 months. Best corrected visual acuity (BCVA), optical coherence tomography (OCT) parameters, and fluorescein angiography (FA) were evaluated. Results Eight eyes (72.7%) in the treatment group and 2 eyes in the control group (40%) showed complete retinal fluid resorption (p=0.049). BCVA showed no significant change from baseline in both the treatment group and the control group (p=0.40 and p=0.29, respectively). Both median central foveal thickness (CFT) and median macular volume showed a greater reduction from baseline in the treatment group. Conclusion In patients showing an incomplete response to anti-VEGF therapy, DXI combined with intravitreal anti-VEGF seems to improve retinal fluid resorption without functional advantage. This trial is registered with ACTRN12618001102268.

Cauterization of Ozurdex wound for the prevention of scleral leakage in vitrectomized eyes

Purpose: To study if cauterization of the scleroconjuctival wound secondary to intravitreal dexamethasone implant in vitrectomized eyes is effective to avoid scleral leakage and hypotony. Methods: A total of 35 vitrectomized eyes of 35 consecutive patients with macular edema who underwent a single intravitreal dexamethasone implant injection in the operating room at the Eye Clinic of the University of Bari, Italy, from 2013 to 2017 were retrospectively reviewed. At the end of the injection, transconjuctival/scleral bipolar cauterization was applied at the injection site and the presence or absence of leakage or hypotony was studied. Results: At the end of the procedure, no patient showed fluid leakage from the cauterized scleroconjuctival wound. No ocular hypotony of other ophthalmic complications were observed at 1 hour and 1 day from injection and intraocular pressure did not change significantly from baseline at 1 hour and 1 day after injection. Conclusions: Cauterization of the scleral wound after intravitreal dexamethasone implant injection in vitrectomized eyes is safe and effective to avoid scleral leakage with secondary hypotony, obtaining a watertight wound closure.