Camilla Alovisi

Treatment for neovascular age related macular degeneration: The state of the art.

With the introduction in the clinical practice of drugs inhibiting vascular endothelial growth factor (VEGF) the visual outcomes of patients with neovascular age related macular degeneration (AMD) dramatically improved. Since 2006 repeated intravitreal injections of anti-VEGF became the standard of care for the treatment of neovascular AMD. This review provides an overview of available data form clinical trials supporting the use of anti-VEGF molecules for the treatment of this condition. Several questions remain open, in particular the regimen of treatment, the frequency of injection, the safety of the different drugs, and the poor response to the treatment in some cases. Therefore, new agents and alternative delivery are currently under evaluation.

Timogel® vs timolol 0.5% ophthalmic solution: efficacy, safety, and acceptance.

Purpose To evaluate the efficacy, safety, and tolerability of Timogel® preservative-free once daily compared to timolol 0.5% ophthalmic solution bid in patients with ocular hypertension (OHT) and patients with primary open-angle glaucoma (POAG). Methods A total of 75 patients with OHT and patients with POAG treated with timolol 0.5% bid with intraocular pressure (IOP) ≤21 mmHg were enrolled. They underwent complete ophthalmologic examination, IOP measurements (at trough and daytime curve), evaluation of side effects, Schirmer test, break-up time [BUT], blood pressure, heart rate, ocular diastolic perfusion pressure measurements, and acceptance (Comparison of Ophthalmic Medications for Tolerability). Patients switched to Timogel® and were re-evaluated 3 months later. The analysis of variance and the Pearson χ2 tests were used to test differences between the treatments. Results Intraocular pressure reduction at trough was 23.6% with timolol 0.5% and 22.3% with Timogel®. No statistical differences were observed in IOP values at trough and in the daytime curve between the 2 treatments. Local and systemic side effects were less frequent with Timogel® (hazard ratio: p<0.05). Patients demonstrated a significant improvement of Schirmer test and BUT (p<0.05) and a reduction of dryness and foreign body sensation (42.6% vs 15.4%; p<0.01) after switching to Timogel®. Mild and short-lasting blurred vision after Timogel® instillation occurred in about 18.5% of patients. A total of 82% of patients were satisfied or very satisfied with Timogel® vs 61% with previous treatment (p<0.01). Conclusions Timogel® preservative-free dosed once every morning has a 24-hour hypotensive effect with a better safety profile than timolol 0.5% bid and it is well-accepted by patients. The once-daily dosing improved acceptance and compliance.

Changing trends in corneal graft surgery: A ten-year review

AIM To review indications and corneal tissue use for penetrating and lamellar surgery between 2002 and 2011. METHODS The surgical reports of corneal grafts performed during 2002-2011, using tissues supplied by the Eye Bank of Piedmont (Italy), were reviewed retrospectively. Patient demographic data, date of intervention, indication for surgery, and surgical technique used were recorded. Surgical techniques included penetrating keratoplasty (PK), deep anterior lamellar keratoplasty (DALK) and endothelial keratoplasty (EK). The χ (2) test was used to compare the distribution of indications and types of surgical technique used, for corneal grafts done during 2002-2006 versus those done during 2007-2011. RESULTS The number of corneal grafts increased by 30.7% from 2002-2006 to 2007-2011 (from 1567 to 2048). Comparing the two periods, both main indications and surgical techniques changed significantly. In 2007-2011, the proportion of interventions for aphakic/pseudophakic bullous keratopathy (from 16.8% to 21.3%), graft failure (from 16.4% to 19.1%) and Fuchs endothelial dystrophy (from 12.8% to 16.7%) all increased significantly (P<0.05), while those for keratoconus decreased significantly (from 35.6% to 27.3%; P<0.001). In 2007-2011, the proportion of PK decreased significantly (from 92.4% to 57.2%; P<0.001) while that of EK and DALK went from 0.4% to 30.2% (P<0.001) and from 7.2% to 12.6% (P<0.001) respectively. CONCLUSION During 2002-2011 the number of interventions increased significantly for corneal endothelial diseases and graft failure. The growing demand for interventions for these diseases corresponded to the widespread adoption of EK techniques. The use of DALK also increased, but more moderately than EK procedures.

Evaluation of Composite Adaptation to Pulpal Chamber Floor Using Optical Coherence Tomography

INTRODUCTION A coronal seal is fundamental for a positive outcome to endodontic therapy. In this in vitro study, we evaluated the adaptation of composite resins in postendodontic restorations using optical coherence tomographic (OCT) imaging. Our null hypothesis was that there would be no difference in marginal adaptation to the pulp chamber floor between resin composites of different viscosities. METHODS Thirty intact upper molars extracted for periodontal reasons were selected, endodontically treated, and filled with gutta-percha. The excess gutta-percha was entirely removed from the pulp chamber floor, and teeth were randomly divided into 3 groups (n = 10) according to the material used for the restoration: group 1: 0.5-mm horizontal layer of flowable composite followed by nanohybrid composite, group 2: bulk layering of bulk fill flowable composite; and group 3: oblique layering of nanohybrid composite. The degree of adaptation to the cavity floor was assessed using OCT imaging, and images were analyzed with the software program ImageJ (National Institutes of Health, Bethesda, MD) to assess the marginal gap between the composite and the pulp chamber floor. Collected data were statistically analyzed using analysis of variance testing, and statistical significance was set at P < .05. RESULTS Flowable composites showed significantly better adaptation than traditional packable nanohybrid composites (P < .05). All significant differences were found between groups 1 and 2. CONCLUSIONS Within the limitations of this OCT imaging-based in vitro study, it was concluded that the flowable composite (flow + nanofilled; flow bulk fill composite) adapted better to the pulp chamber floor than the packable nanohybrid composite resin. Further studies are necessary to confirm these results.

Targeted next generation sequencing in Italian patients with Usher syndrome: phenotype-genotype correlations

We report results of DNA analysis with next generation sequencing (NGS) of 21 consecutive Italian patients from 17 unrelated families with clinical diagnosis of Usher syndrome (4 USH1 and 17 USH2) searching for mutations in 11 genes: MYO7A, CDH23, PCDH15, USH1C, USH1G, USH2A, ADGVR1, DFNB31, CLRN1, PDZD7, HARS. Likely causative mutations were found in all patients: 25 pathogenic variants, 18 previously reported and 7 novel, were identified in three genes (USH2A, MYO7A, ADGRV1). All USH1 presented biallelic MYO7A mutations, one USH2 exhibited ADGRV1 mutations, whereas 16 USH2 displayed USH2A mutations. USH1 patients experienced hearing problems very early in life, followed by visual impairment at 1, 4 and 6 years. Visual symptoms were noticed at age 20 in a patient with homozygous novel MYO7A missense mutation c.849G > A. USH2 patients’ auditory symptoms, instead, arose between 11 months and 14 years, while visual impairment occurred later on. A homozygous c.5933_5940del;5950_5960dup in USH2A was detected in one patient with early deafness. One patient with homozygous deletion from exon 23 to 32 in USH2A suffered early visual symptoms. Therefore, the type of mutation in USH2A and MYO7A genes seems to affect the age at which both auditory and visual impairment occur in patients with USH.

Indocyanine Green Angiography and Optical Coherence Tomography Angiography of Choroidal Neovascularization in Age-Related Macular Degeneration

Purpose To compare the capability of indocyanine green angiography (ICGA) and optical coherence tomography angiography (OCTA) in detecting choroidal neovascularization (CNV). Methods In this prospective study, patients with CNV detected with fluorescein angiography (FA) underwent ICGA and OCTA, spectral domain OCT (SD-OCT), and infrared or fundus color photographs. CNV lesions were outlined on ICGA and OCTA images, and the composition and size of the CNV was documented. Results One hundred eighty-two eyes were included. With ICGA, well-defined lesions were observed in 37.9%, partly defined in 44.5%, and undefined in 17% of eyes. On OCTA, well-defined, partly defined, and undefined vessels were observed in 53.8%, 27.5%, and 18.7% of eyes, respectively. There was a good correlation between CNV size measured with the two instruments (r = 0.84). However, OCTA underestimated CNV area by about 4.5% (slope coefficient with linear regression: 0.55, 95% confidence interval [CI]: 0.46 to 0.65; intercept: 0.27, 95% CI: -0.2 to 0.56). On ICGA, CNV composition was capillary in 28%, mature in 14.3%, and mixed (capillary and major neovascular complex) in 57.7% of eyes. Similarly, OCTA revealed capillary, mature, and mixed CNV in 28.9%, 15.9%, and 55.5% of eyes, respectively. Conclusions OCTA provides the clinician the ability to perform precise structural and vascular assessment of CNV noninvasively. Our study is, to our knowledge, the largest OCTA analysis to date of CNV secondary to neovascular AMD analyzed simultaneously by ICGA and OCTA.

Macular Pigment Density and Quantitative Fundus Autofluorescence in Young Healthy Subjects

Purpose To measure macular pigment (MP) and find possible correlation between heterochromatic flicker photometry (HFP) and quantitative autofluorescence (qAF) in young healthy subjects. Methods We enrolled 80 eyes of 40 young healthy subjects. Macular pigment optical density (MPOD) was automatically calculated with a macular pigment screener (MPS; MPODHFP). We calculated qAF comparing gray levels (GL) of qAF images with GL of internal reference of a confocal scanning laser ophthalmoscopy. A raster of concentric rings was used to automatically calculate foveal qAF (qAFF) values (0°-1.2°); inner ring (1.3°-4.3°; qAF3); middle ring (4.5°-7°; qAF6); and outer ring (7.2°-9.7°; qAF8). The test-retest coefficient of repeatability was calculated with Bland-Altman method. The between-eyes coefficient of agreement and correlation between the two techniques were calculated. Finally, an estimation of MPOD from qAF was performed (MPOD-AF), to find possible direct correlations with MPODHFP obtained with the MPS II. Results Paired data sets of repeated measurements were not statistically different for MPS II (P = 0.66); log qAFF (P = 0.95); log qAF3 (P = 0.48); log qAF6 (P = 0.4); and log qAF8 (P = 0.56). Stepwise regression analysis showed negative correlation between MPS II and log qAFF values (R2 = 0.35) with Spearman coefficient (ρ) of -0.60 (P < 0.01) and log qAF3 (R2 = 0.18; ρ = -0.38.; P < 0.01). No correlation was found between MPS II and log qAF6 (ρ = 0.01, P = 0.93), neither with log qAF8 (ρ = -0.05, P = 0.66). Conclusions In young healthy subjects, a negative correlation between qAF values and MPODHFP was found in the central degrees. However, qAF and HFP do not seem to be interchangeable: they represent two opposite ways of estimating MP.

Short-Term Choriocapillaris Changes in Patients with Central Serous Chorioretinopathy after Half-Dose Photodynamic Therapy

Background: Although photodynamic therapy (PDT) has become the standard treatment for central serous chorioretinopathy (CSC), its mechanism of action remains unclear. It is assumed that PDT induces short-term choriocapillaris (CC) occlusion and long-term choroidal vascular remodeling. In this paper, we describe the short-term CC changes induced by Half-Dose PDT (HD-PDT) in chronic CSC using optical coherence tomography-angiography (OCTA). Methods: This is a prospective interventional case series. Chronic CSC eyes underwent Spectral-Domain OCT, Fundus Autofluorescence, FA, ICGA (Heidelberg Spectralis, Heidelberg, Germany) and OCTA (RTVue XR Avanti with AngioVue; Optovue Inc., Fremont, CA, USA) before HD-PDT, with follow-up after one hour, one week, and one month. Vascular changes after PDT were analyzed within the CC layer. The CC vessel density was defined as the percentage of an area occupied by flow pixels, using Image J software to obtain measurements by applying a grey level threshold. All pixels with a grey level above the threshold were considered as indicators of blood flow. Results: 20 eyes of 19 patients were included. At baseline the mean CC vessel density was 94.87 ± 2.32%. It significantly differed from the density at 1 week and 1 month (92.79 ± 3.16% and 95.55 ± 2.05%, p < 0.001, respectively), but not with values at 1 h (94.8 ± 2.28%, p = 0.516). Conclusions: CC vessel density was significantly reduced at 1 week as compared with baseline, suggesting a possible short-term effect of PDT on CC perfusion. After 1 month however, the CC vessel density was even higher than the baseline, probably due to a CC recovery. OCTA seems to be useful in the visualization of CC vessels and in confirming the mechanism of action of PDT treatment in eyes with chronic CSC.

Vitreous Substitutes: Old and New Materials in Vitreoretinal Surgery

Recent developments in vitreoretinal surgery have increased the need for suitable vitreous substitutes. A successful substitute should maintain all the physical and biochemical properties of the original vitreous, be easy to manipulate, and be long lasting. Substitutes can be gaseous or liquid, both of which have associated advantages and disadvantages related to their physical properties and use. Furthermore, new surgical techniques with smaller vitreoretinal instruments have driven the use of more viscous substitutes. In this review, we analyze and discuss the most frequently used vitreous substitutes and look ahead to future alternatives. We classify these compounds based on their composition and structure, discuss their clinical use with respect to their associated advantages and disadvantages, and analyze how new vitreoretinal surgical techniques have modified their use.