Federico Ricci

PREVALENCE OF BLINDNESS AND LOW VISION IN AN ITALIAN POPULATION: A COMPARISON WITH OTHER EUROPEAN STUDIES

AimThe scientific literature contains recent data on the prevalence of blindness and low vision for a few European countries, but most of these studies have been focused exclusively on the elderly sector of the populations. The purpose of the present study was to provide age-specific estimates of the prevalence and causes of visual loss in an Italian population aged 40 years and over.MethodsIn total, 847 of the 1200 citizens >40 years of age (70.6%) in the island community of Ponza underwent complete standardized ophthalmological examinations. Visual acuity (VA) was measured using a standard logarithmic chart. World health organization (WHO) definitions of blindness and low vision were adopted (respectively, VA>1.3 logMAR or a visual field <10° around central fixation, and VA >0.5 to 1.3 logMAR or a visual field <20° around central fixation). Prevalence rates based on presenting VAs were also calculated.ResultsThe overall best-corrected prevalence rates were 0.6% (presenting, 0.8%) for better eye blindness, 2.1% (presenting, 6.7%) for better eye low vision, 1.8% (presenting, 2.6%) for monocular blindness, 5.0% (presenting, 11.2%) for monocular low vision. Cataract, glaucoma, degenerative myopia, and AMD were the main causes of better eye visual loss.ConclusionAge-specific prevalence rates in Ponza are fairly consistent with those for other European countries with similar socio-economic conditions and public healthcare systems. A substantial percentage of visual losses remains uncorrected despite the availability of potentially curative therapy. Greater emphasis needs to be placed on educating the public regarding the importance of good vision.

Spectral domain optical coherence tomography findings in patients with acute syphilitic posterior placoid chorioretinopathy.

Purpose: To describe the appearance of acute syphilitic posterior placoid chorioretinitis, a rare ocular manifestation of syphilis, on spectral domain optical coherence tomography (SD OCT) both before and after treatment. Methods: Ophthalmic examination and imaging studies of 30 eyes of 19 confirmed cases were analyzed both at the time of presentation and at each follow-up visit. Patients with SD OCT and fluorescein angiography at the time of presentation, and at least three documented follow-up visits after initiation of therapy, were included in the study. Standard treatment of neurosyphilis was given to each patient, including 4 million units of penicillin G administered intravenously every 4 hours for 14 days. Results: Fundus examination and imaging studies were consistent with previous reports and confirmed the diagnosis of acute syphilitic posterior placoid chorioretinitis. In 13 eyes (43.3%), baseline SD OCT scans were performed within 1 to 2 days of presentation and revealed a small amount of subretinal fluid, disruption of the inner segment/outer segment junction, and hyperreflective thickening of the retinal pigment epithelium (RPE). All 30 eyes were again scanned between Days 7 and 9 after presentation and revealed loss of the inner segment/outer segment and OS/RPE bands, and irregular hyperreflectivity of the RPE with prominent nodular elevations but without subretinal fluid. Early disruption of the external limiting membrane and punctate choroidal hyperreflectivity were seen in 1 of the 30 eyes (3.3%) and 14 of the 30 eyes (46.6%), respectively. Vision improved and the outer retinal abnormalities normalized in 28 of the 30 eyes (93.3%) after the treatment of neurosyphilis. The external limiting membrane, inner segment/outer segment band, and/or linear outer segment/RPE junction remained substantially abnormal despite treatment in 2 eyes left with 20/200 vision. Conclusion: Patients with acute syphilitic posterior placoid chorioretinitis show characteristic outer retinal abnormalities on SD OCT imaging, including disruption of the inner segment/outer segment band, nodular thickening of the RPE with loss of the linear outer segment/RPE junction, and, in some cases, loss of the external limiting membrane, accumulation of subretinal fluid, and punctate hyperreflectivity in the choroid. Vision improved and these abnormalities reversed after treatment of neurosyphilis in most of the patients. Persistently, poor vision despite treatment was associated with long-term loss or disruption of outer retinal anatomy on SD OCT.

Clusterin in stool: a new biomarker for colon cancer screening?

OBJECTIVES:The identification of useful markers for early diagnosis of human colon cancer is a major goal still in progress. Clusterin is a pleiotropic protein with a broad range of functions. It has recently drawn much attention because of its association with cancer promotion and metastasis. It is involved in prosurvival and apoptosis processes that are carried out by two different isoforms. Secreted clusterin isoform (sCLU) is cytoprotective and its prosurvival function is the basis of the current phase I/II clinical trials against prostate, lung, and breast cancers. We have already shown that in colorectal cancer (CRC) there is an increased expression of sCLU. In this report, we investigated whether sCLU is released in the blood and stool of colon cancer patients in order to study sCLU as a potential diagnostic molecular marker for colon cancer screening.METHODS:The quantitative expression of sCLU was determined by dot blot immunodosage in the serum and stool of CRC patients (n=63) and age-matched controls without clinical history of neoplasia, CRC, or systemic or bowel inflammatory disease (n=50). Unpaired t-tests and Mann–Whitney U-tests were used for continuous variables. The diagnostic performance of clusterin was appraised by means of receiver operating characteristic (ROC) curves.RESULTS:We found a significant increase of sCLU in the serum and stool of CRC patients (P=0.0002 and P<0.000, respectively) as compared with controls. ROC curves provided cutoff points showing a trade-off between sensitivity and specificity. With a cutoff point of 88.5 μg/ml, sCLU in blood showed a 55.6% sensitivity and 100% specificity, and with a cutoff point of 34.6 μg/g, the stool test reached 66.7% sensitivity and 84% specificity in discriminating between nonneoplastic and colorectal neoplastic lesions. Human cancer xenografts in nude mice indicated a positive correlation between increasing serum clusterin level and tumor size.CONCLUSIONS:This study highlights the potential of clusterin detection in stool to be a valuable tool to improve the effectiveness and efficiency of large-scale clinical cancer screening.

Ranibizumab 0.5 mg treat-and-extend regimen for diabetic macular oedema: the RETAIN study

Aims To demonstrate non-inferiority of ranibizumab treat-and-extend (T&E) with/without laser to ranibizumab pro re nata (PRN) for best-corrected visual acuity (BCVA) in patients with diabetic macular oedema (DMO). Methods A 24-month single-masked study with patients randomised 1:1:1 to T&E+laser (n=121), T&E (n=128) or PRN (control; n=123). All patients received monthly injections until BCVA stabilisation. The investigator decided on re-treatment in the PRN and treatment-interval adaptations in the T&E groups based on loss of BCVA stability due to DMO activity. Likewise, laser treatment was at investigators discretion. Collectively, these features reflect a real-life scenario. Endpoints included mean average change in BCVA from baseline to months 1–12 (primary), mean BCVA change from baseline to months 12 and 24, treatment exposure and safety profile. Results Both T&E regimens were non-inferior to PRN based on mean average BCVA change from baseline to months 1–12 (T&E+laser: +5.9 and T&E: +6.1 vs PRN: +6.2 letters; both p<0.0001). Mean BCVA change at month 24 was similar across groups (+8.3, +6.5 and +8.1 letters, respectively). The mean number of injections was 12.4 and 12.8 in the T&E+laser and T&E groups and 10.7 in the PRN group. The T&E regimens showed 46% reduction in the number of clinic visits. Over 70% of patients maintained their BCVA, with treatment intervals of ≥2 months over 24 months. Safety profile was consistent with that described in the product information. Conclusions T&E is a feasible treatment option for patients with DMO, with a potential to reduce treatment burden. Slightly more injections were required versus PRN, likely due to the specifics of the T&E regimen applied here. Trial registration number NCT01171976.

Review of nutrient actions on age-related macular degeneration.

The actions of nutrients and related compounds on age-related macular degeneration (AMD) are explained in this review. The findings from 80 studies published since 2003 on the association between diet and supplements in AMD were reviewed. Antioxidants and other nutrients with an effect on AMD susceptibility include carotenoids (lutein and zeaxanthin, β-carotene), vitamins (vitamin A, E, C, D, B), mineral supplements (zinc, copper, selenium), dietary fatty acids [monounsaturated fatty acids, polyunsaturated fatty acids (PUFA both omega-3 PUFA and omega-6 PUFA), saturated fatty acids and cholesterol], and dietary carbohydrates. The literature revealed that many of these antioxidants and nutrients exert a protective role by functioning synergistically. Specifically, the use of dietary supplements with targeted actions can provide minimal benefits on the onset or progression of AMD; however, this does not appear to be particularly beneficial in healthy people. Furthermore, some supplements or nutrients have demonstrated discordant effects on AMD in some studies. Since intake of dietary supplements, as well as exposure to damaging environmental factors, is largely dependent on population habits (including dietary practices) and geographical localization, an overall healthy diet appears to be the best strategy in reducing the risk of developing AMD. As of now, the precise mechanism of action of certain nutrients in AMD prevention remains unclear. Thus, future studies are required to examine the effects that nutrients have on AMD and to determine which factors are most strongly correlated with reducing the risk of AMD or preventing its progression.

Typing of ARMS2 and CFH in age-related macular degeneration: case-control study and assessment of frequency in the Italian population.

OBJECTIVES To determine the effects of the polymorphisms CFH Tyr402His and ARMS2 del443ins54 on susceptibility to age-related macular degeneration (AMD) and to find the frequencies of these single-nucleotide polymorphisms in an Italian population that was not examined clinically. METHODS A total of 286 control subjects (126 men and 160 women) and 159 white patients (73 men and 86 women) harboring exudative AMD in 1 eye were recruited. A third group of 182 DNA samples from blood donors of the same geographical areas were also typed to assess the frequency of CFH Tyr402His and ARMS2 del443ins54 polymorphisms in the general population. The data were analyzed statistically by a standard 2 x 2 table, Fisher exact tests, and odds ratios. RESULTS The deletion-insertion at chromosome 10q26 (del443ins54) showed the strongest association with AMD in terms of both P value and odds ratio (P = 2.7 x 10(-15); odds ratio = 3.25), and a highly significant association was also confirmed for Tyr402His at the CFH locus (P = 9.9 x 10(-13); odds ratio = 2.86). We found no differences in allele and genotype association between classic and occult choroidal neovascularization. We also observed that 39% of the samples in the general Italian population were at least 5.4 times more likely than control subjects to develop AMD. CONCLUSIONS To our knowledge, this is the first confirmation of the association of del443ins54 in Italian patients with AMD, and we also confirmed the association of Tyr402His with CFH. Genetic analysis of the general population suggested that analysis of the ARMS2 and CFH risk alleles alone may be helpful in differentiating high-risk individuals (odds ratio > 5.00) from low-risk individuals (odds ratio < 0.45). CLINICAL RELEVANCE Individuals at high risk for developing AMD could be identified and selected for specific prevention programs. In this context, the development of prevention programs based on dietary antioxidants or on close monitoring of at-risk individuals should be considered or suggested.

Age-Related Macular Degeneration: Insights into Inflammatory Genes

Age-related macular degeneration (AMD) is a progressive neurodegenerative disease that affects approximately 8.7% of elderly people worldwide (>55 years old). AMD is characterized by a multifactorial aetiology that involves several genetic and environmental risk factors (genes, ageing, smoking, family history, dietary habits, oxidative stress, and hypertension). In particular, ageing and cigarette smoking (including oxidative compounds and reactive oxygen species) have been shown to significantly increase susceptibility to the disease. Furthermore, different genes (CFH, CFI, C2, C3, IL-6, IL-8, and ARMS2) that play a crucial role in the inflammatory pathway have been associated with AMD risk. Several genetic and molecular studies have indicated the participation of inflammatory molecules (cytokines and chemokines), immune cells (macrophages), and complement proteins in the development and progression of the disease. Taking into consideration the genetic and molecular background, this review highlights the genetic role of inflammatory genes involved in AMD pathogenesis and progression.

Haplotypes in IL-8 Gene Are Associated to Age-Related Macular Degeneration: A Case-Control Study

Background Age-related macular degeneration (AMD) is the main cause of blindness in the developed world. The etiology of AMD is multifactorial due to the interaction between genetic and environmental factors. IL-8 has a role in inflammation and angiogenesis; we report the genetic characterization of IL-8 allele architecture and evaluate the role of SNPs or haplotypes in the susceptibility to wet AMD, case-control study. Methods Case-control study including 721 AMD patients and 660 controls becoming from Italian population. Genotyping was carried out by Real Time-PCR. Differences in the frequencies were estimated by the chi-square test. Direct sequencing was carried out by capillary electrophoresis trough ABI3130xl. Results rs2227306 showed a p–value of 4.15*10−5 and an Odds Ratio (OR) for T allele of 1.39 [1.19–1.62]. After these positive results, we sequenced the entire IL-8 regulatory and coding regions of 60 patients and 30 controls stratified for their genotype at rs2227306. We defined two different haplotypes involving rs4073 (A/T), rs2227306 (C/T), rs2227346 (C/T) and rs1126647 (A/T): A-T-T-T (p-value: 2.08*10−9; OR: 1.68 [1.43–1.97]) and T-C-C-A (p-value: 7.07*10−11; OR: 0.60 [0.51–0.70]). To further investigate a potential functional role of associated haplotypes, we performed an expression study on RNA extracted from whole blood of 75 donors to verify a possible direct correlation between haplotype and gene expression, failing to reveal significant differences. Conclusions These results suggest a possible secondary role of IL-8 gene in the development of the disease. This paper outlines the importance of association between inflammation and AMD. Moreover IL-8 is a new susceptibility genomic biomarker of AMD.

Validity and limitations of the Nidek NT-4000 non-contact tonometer: a clinical study

Using Goldmann applanation tonometry (GAT) as a gold standard, we evaluated the accuracy of Nidek NT‐4000 pneumotonometry (NPT) in adults without corneal disease. Bland and Altman analysis of serial intra‐ocular pressures (IOPs) measured with NPT and GAT in 10 healthy subjects revealed that the repeatability coefficients for the two methods were similar. NPT, GAT and ultrasonic pachymetry were then performed in 100 patients. Bland and Altman analysis showed that NPT yielded significantly higher readings than GAT [mean biases for right and left eye measurements were 1.37 mmHg (95% limits of agreement: −3.02–5.76) and 1.17 mmHg (95% limits of agreement: −2.76–5.11) respectively] and was more affected by corneal thickness variations. For detection of IOPs ≥21 mmHg, NPT displayed very high sensitivity (0.90) and good specificity (0.95). NPT may be useful in screening and clinical settings but borderline‐high IOP readings should be confirmed with GAT.

Indocyanine green dye-enhanced micropulsed diode laser: a novel approach to subthreshold RPE treatment in a case of central serous chorioretinopathy

Purpose To present a case of central serous chorioretinopathy (CSC) treated with indocyanine green (ICG) dye-enhanced subthreshold micropulsed diode laser photocoagulation. METHODS CASE REPORT A 35-year-old man presenting with recurrent CSC with persistent serous detachment of the sensory retina in his left eye who declined treatment with a 532 nm laser. Subthreshold treatment, with no visible endpoint, was performed with an 810 nm diode laser 15 minutes after the injection of 25 mg ICG in 2 cc of 5% glucose solution. The laser energy was delivered over the active leakage sites with a sequence of repeated 500 ms “envelopes” each containing a train of 250 micropulses with 500 mW peak power at 10% duty cycle (200 μs ON and 1,800 μs OFF) and each separated by 500 ms intra-envelopes relaxation time. Due to the absence of visible laser-induced lesions, post treatment ICG digital angiographic images were taken without further dye injection to verify that the hypofluorescent spots resulting from the subthreshold laser applications coincided with the points of leakage. Results After 7 days, the patient presented with a less hyperopic refraction, improved visual acuity, and reduction of serous neuroepithelial detachment. No signs of laser treatment were visible at fluorescein angiography. After 8 weeks, the serous neuroepithelial detachment was almost completely resolved. CONCLUSIONS ICG dye-enhanced subthreshold micropulsed diode laser photocoagulation appears to be a safe and effective treatment and tepresents a possible approach for the management of chronic CSC with persistent central serous neuroepithelial detachment. Immediate post treatment ICG angiography, without ICG reinjection, allows documenting the actual number and location of the delivered subthreshold laser applications.