Simone Donati

Combined intravitreal bevacizumab and grid laser photocoagulation for macular edema secondary to branch retinal vein occlusion.

Purpose To evaluate long-term efficacy of intravitreal bevacizumab (IVB) versus combined IVB and macular grid laser photocoagulation for the treatment of macular edema secondary to branch retinal vein occlusion (BRVO). Methods In this prospective study, 18 eyes were randomized into 2 groups according to treatment: Group 1 (9 eyes) underwent IVB at baseline, at month 1, and at month 2; Group 2 (9 eyes) underwent same IVB protocol combined with macular grid laser photocoagulation. Macular edema and visual acuity represented the endpoints of the study. IVB reinjections were performed in both groups if recurrent macular edema was diagnosed. Spectral domain optical coherence tomography examination as well as visual acuity examination were performed during follow-up. Statistical evaluation was performed for a matched-pair analysis. Results In Group 1, median baseline central retinal thickness (CRT) decreased from 420 μm (95% confidence interval 355.6-484.4) to 323 μm (261.44-384.56) at month 12 (p=0.06); median baseline BCVA improved from 0.7 logMAR (0.54-0.86) to 0.4 logMAR (0.29-0.51) at month 12 (p<0.01). In Group 2, baseline CRT decreased from 386 μm (353.91-418.09) to 238 μm (200.58-275.42) at month 12 (p<0.01); median BCVA improved from 0.6 logMAR (0.45-0.75) to 0.2 logMAR (0.12-0.28) at month 12 (p<0.01). A statistically significant difference (p=0.03) was found regarding the median number of injections (Group 1: 4±1.1; Group 2: 3±0.4). Conclusions Both treatment modalities appeared effective to control BRVO-induced macular edema. In the combined-treatment Group, we observed a lower number of reinjections during follow-up, suggesting the efficacy of grid laser photocoagulation to reduce the number of intravitreal injections and maintain short- and long-term results of the therapy.

Vitreous Substitutes: The Present and the Future.

Vitreoretinal surgery has advanced in numerous directions during recent years. The removal of the vitreous body is one of the main characteristics of this surgical procedure. Several molecules have been tested in the past to fill the vitreous cavity and to mimic its functions. We here review the currently available vitreous substitutes, focusing on their molecular properties and functions, together with their adverse effects. Afterwards we describe the characteristics of the ideal vitreous substitute. The challenges facing every ophthalmology researcher are to reach a long-term intraocular permanence of vitreous substitute with total inertness of the molecule injected and the control of inflammatory reactions. We report new polymers with gelification characteristics and smart hydrogels representing the future of vitreoretinal surgery. Finally, we describe the current studies on vitreous regeneration and cell cultures to create new intraocular gels with optimal biocompatibility and rheological properties.

Consensus on the diagnosis, treatment and follow-up of patients with age-related macular degeneration eligible for ranibizumab

Age-related macular degeneration (AMD) is an irreversible pathology that is the principal cause of serious loss of central vision and legal blindness among people over 60 years of age. There are two forms of AMD: the dry, or atrophic form, and the wet, neovascular form. The latter is less frequent but is the cause of approximately 80–90% of cases of serious loss of vision in a short time period. Early diagnosis is therefore essential to permit intervention as promptly as possible. Currently, the most effective therapy for neovascular AMD uses the new class of anti-VEGF drugs, and ranibizumab is today’s ‘gold standard’ for this treatment. The Progetto LUCE (LUCE Project) consists of an advisory board of retinal disease specialists in Lombardy, Italy, whose task is to propose a consensus for the diagnosis, treatment and follow-up of neovascular AMD patients treated with ranibizumab on the basis of a review of the scientific evidence and Italian national health service regulations and the clinical experience of the advisory board members.

Expression of VEGF-A, Otx homeobox and p53 family genes in proliferative vitreoretinopathy.

Introduction. Proliferative vitreoretinopathy (PVR) is a severe inflammatory complication of retinal detachment. Pathological epiretinal membranes grow on the retina surface leading to contraction, and surgery fails in 5% to 10% of the cases. We evaluated the expression of VEGF-A, Otx1, Otx2, Otx3, and p53 family members from PVR specimens to correlate their role in inducing or preventing the pathology. Methods. Twelve retinal samples were taken from patients affected by PVR during therapeutic retinectomies in vitreoretinal surgery. Gene expression was evaluated using quantitative real-time reverse transcriptase PCR analysis and immunohistochemistry, using four healthy human retinae as control. Result. Controls showed basal expression of all genes. PVR samples showed little or no expression of Otx1 and variable expression of VEGF-A, Otx2, Otx3, p53, and p63 genes. Significant correlation was found among VEGF-A, Otx2, p53, and p63 and between Otx1 and Otx3. Conclusions. Otx homeobox, p53 family, and VEGF-A genes are expressed in PVR human retina. We individuated two possible pathways (VEGF-A, Otx2, p53, p63 and Otx1 and Otx3) involved in PVR progression that could influence in different manners the course of the pathology. Individuating the genetic pathways of PVR represents a novel approach to PVR therapies.

Clinical analysis of macular edema with new software for SD-OCT imaging

Purpose To evaluate the clinical efficacy of user-friendly software for the measurement of intraretinal hyporeflective spaces expression of macular edema. Methods Fifteen consecutive patients with diabetic retinopathy with clinically significant macular edema were examined using conventional spectral domain optical coherence tomography (OCT). A new composite software application, OCT–measurement analysis tool (OCT-MAT), was developed to automatically process and analyze OCT B-scans by means of image acquisition, filtering, and elaboration, together with hyporeflective area recognition and measurement in μm2. The same macular areas were measured manually, and then compared to the measurements obtained by the automated OCT-MAT software. A statistical t test analysis was applied (statistical significance level at p<0.05). The repeatability and reproducibility coefficient for the automated software was computed using the Wilcoxon matched pair test (5% significance level). Results In all patients, the software effectively measured the number and extension of intraretinal hyporeflective spaces in μm2. The comparison between mean manual measurements and OCT-MAT measurements (0.478 ± 0.300 × 106 μm2 vs 0.471 ± 0.321 × 106 μm2) showed correct correspondence (p>0.05). Moreover, the OCT-MAT software showed good repeatability and reproducibility (coefficient below 3%). Conclusions OCT-MAT allows the precise measurement of macular edema in terms of the number of empty spaces and their size in all patients. Its daily clinical application might give precise information regarding the evolution of macular edema and the efficacy of therapy.

Heavy and standard silicone oil: intraocular inflammation

PurposeProliferative vitreoretinopathy in the inferior retina remains clinically challenging. Heavier-than-water intraocular tamponades have been developed to improve inferior tamponading properties, and their chemical compositions have been substantially improved over the years, in parallel with developments in vitrectomy instrumentation and surgical techniques. Herein we present an updated review of the clinical use of standard formulations and HSO, focusing on analysis of the intraocular inflammation associated with endotamponade agents, and comparison of the adverse effects of these agents on the physical and biological properties of the eye.MethodsA detailed literature search was conducted on PubMed, EMBASE, Cochrane Library, and Google Scholar using the key words. Fifty-eight articles matched our inclusion criteria that were included in this systematic review.ResultsPerfluorocarbon liquids and partially fluorinated alkanes are associated with tamponade emulsification, intraocular inflammation, and rises in intraocular pressure, but these associations are not as strong when these substances are mixed with a heavy silicone oil (HSO). Two recently approved heavy silicone oil tamponades, Oxane HD and Densiron 68, are now available for use in clinical practice. While the complication spectrum of the new generation of these HSOs seems to be similar to that of conventional silicone oil tamponades, they provide better support for the inferior retina and the posterior pole.ConclusionBoth regular and heavy silicone oils usually yield good success rates in cases of complicated retinal detachment. Decisions as to whether to utilize heavy or regular silicone oil should be made on a case-by-case basis.

Erythropoietin and Diabetic Retinopathy

Diabetic retinopathy (DR) is the main cause of visual impairment in industrialized countries. Great efforts are in place to search for new therapies able to prevent the development of DR and the onset of its complications. At present, therapy consists of anti-VEGF intra vitreal injections and is aimed at preventing the main causes of visual impairment, that is, macular oedema and retinal proliferation. However, the current knowledge has led us to hypothesize about the roles of other factors implicated in the pathogenesis of macular oedema and retinal proliferation; erythropoietin (EPO) is one such compound. The aim of the work was to review the recent literature on the applications of EPO within the context of DR etiopathogenicity.

A teleconsultation network improves the efficacy of anti-VEGF therapy in retinal diseases

We investigated the care of patients with age-related macular degeneration (AMD) managed via a physician-to-physician teleconsultation network for ophthalmology. Eleven groups of ophthalmologists took part in the study. The groups were located in 10 cities across Italy. Each group was based on a Retina Centre located at a university or hospital, with one or two expert ophthalmologists (20 expert ophthalmologists in total). In each region containing a Retina Centre, 6-10 general ophthalmologists (94 ophthalmologists in total) referred patients via the network for a period of three months between June 2011 and December 2012. An automatic grading system quantified the risk of disease progression, and a remote booking system allowed the referring ophthalmologist to make appointments directly with the appropriate Retina Centre. There were 360 network patients and 318 control patients (consecutive patients undergoing usual care during the previous three months). The time delay before therapy was significantly shorter in the network patients (mean 5.5 days) compared with the usual care patients (mean 28.7 days; P < 0.0001). There was a significant improvement in visual acuity in the network patients after treatment (first visit = 0.29 logMAR; after treatment = 0.22 logMAR; P < 0.05). In contrast, there was no improvement in the usual care patients (first visit = 0.29 logMAR; after treatment = 0.27 logMAR; P > 0.05). The telemedicine network allows regional ophthalmologists to quantify the risk of disease progression, and to send patients to a Retina Centre quickly and easily, when required.

Prevalence of macular abnormalities assessed by optical coherence tomography in patients with Usher syndrome

ABSTRACT Background: To investigate the prevalence of macular abnormalities in patients affected by Usher syndrome (USH), by comparing the clinical findings between two types (i.e., USH1 and USH2). Material and methods: A retrospective study was performed by reviewing optical coherence tomography (OCT) in 134 USH patients to determine the presence of macular abnormalities, including cystoid macular edema (CME), epiretinal membrane (ERM), vitreo-macular traction syndrome (VMT), and macular hole (MH). Results: Macular abnormalities were observed in 126/268 (47.0%) examined eyes. The most frequent abnormality was ERM observed in 51 eyes (19%), followed by CME observed in 42 eyes (15.7%). Moreover, CME was significantly (p < 0.05) associated with younger age (CME: 30.1 ± 11.1 years; without CME: 36.9 ± 14.9 years), whereas VMT and full thickness MH were associated with older age (p < 0.05). Moreover, a significantly (p < 0.05) decreased best-corrected visual acuity was associated with MH compared to eyes without MH. Finally, CME was more frequent in USH1 compared to USH2. Conclusion: Our study, for the first time in the literature, showed the distribution of all macular abnormalities assessed by SD-OCT in a large USH cohort, comparing USH1 and USH2 patients. We observed that ocular abnormalities are highly prevalent in USH patients compared to general population, with ERM and CME being the most common alterations. Based on these findings, OCT screening in USH patients is recommended for early detection of macular changes and early treatment.

Morphological and Functional Retinal Assessment in Epiretinal Membrane Surgery.

ABSTRACT Purpose: To analyze functional and morphological findings after surgery for idiopathic epiretinal macular membrane (IEMM). Materials and Methods: Twenty eyes of 20 patients affected by IEMM underwent 23-Gauge surgery. Morphological and functional examinations were assessed at baseline and at 30, 90, and 180 days after surgery. SD-OCT evaluated foveal morphology and thickness, photoreceptor inner/outer segment junction, and external limiting membrane. Functional assessment evaluated visual acuity, retinal sensitivity, and fixation patterns. Statistical analysis was performed with the Student’s t test and Pearson correlation test. Results: Mean central retinal thickness (CRT), visual acuity (VA), and retinal sensitivity (RS) at baseline were respectively 494.90 ± 38.73 µm, 0.55 ± 0.08 LogMAR, and 11.13±1.02; after surgery, at day 180, we observed a significant decrease in mean CRT to 326.90±32.68 µm, an increase in mean VA to 0.33 ± 0.05 LogMAR (p < 0.05), and in mean RS to 13.25 ± 0.73 dB (p < 0.05). A stable fixation increased from 40% of patients at baseline to 75% of patients at day 180 (p < 0.05). Discussion: IEMM surgery results in continuous improvement in visual function, not only at month one but also beyond month six, due to the progressive reduction of residual intraretinal edema and recomposition of retinal layers.