Claudio Campa

Automated Segmentation of Foveal Avascular Zone in Fundus Fluorescein Angiography

PURPOSE. To describe and evaluate the performance of a computerized automated segmentation technique for use in quantification of the foveal avascular zone (FAZ). METHODS. A computerized technique for automated segmentation of the FAZ using images from fundus fluorescein angiography (FFA) was applied to 26 transit-phase images obtained from patients with various grades of diabetic retinopathy. The area containing the FAZ zone was first extracted from the original image and smoothed by a Gaussian kernel (sigma = 1.5). An initializing contour was manually placed inside the FAZ of the smoothed image and iteratively moved by the segmentation program toward the FAZ boundary. Five tests with different initializing curves were run on each of 26 images to assess reproducibility. The accuracy of the program was also validated by comparing results obtained by the program with the FAZ boundaries manually delineated by medical retina specialists. Interobserver performance was then evaluated by comparing delineations from two of the experts. RESULTS. One-way analysis of variance indicated that the disparities between different tests were not statistically significant, signifying excellent reproducibility for the computer program. There was a statistically significant linear correlation between the results obtained by automation and manual delineations by experts. CONCLUSIONS. This automated segmentation program can produce highly reproducible results that are comparable to those made by clinical experts. It has the potential to assist in the detection and management of foveal ischemia and to be integrated into automated grading systems.

Inflammatory Mediators and Angiogenic Factors in Choroidal Neovascularization: Pathogenetic Interactions and Therapeutic Implications

Choroidal neovascularization (CNV) is a common and severe complication in heterogeneous diseases affecting the posterior segment of the eye, the most frequent being represented by age-related macular degeneration. Although the term may suggest just a vascular pathological condition, CNV is more properly definable as an aberrant tissue invasion of endothelial and inflammatory cells, in which both angiogenesis and inflammation are involved. Experimental and clinical evidences show that vascular endothelial growth factor is a key signal in promoting angiogenesis. However, many other molecules, distinctive of the inflammatory response, act as neovascular activators in CNV. These include fibroblast growth factor, transforming growth factor, tumor necrosis factor, interleukins, and complement. This paper reviews the role of inflammatory mediators and angiogenic factors in the development of CNV, proposing pathogenetic assumptions of mutual interaction. As an extension of this concept, new therapeutic approaches geared to have an effect on both the vascular and the extravascular components of CNV are discussed.

Coagulation Gene Predictors of Photodynamic Therapy for Occult Choroidal Neovascularization in Age-Related Macular Degeneration

PURPOSE To determine whether different coagulation-balance genetic polymorphisms explain the variable clinical outcomes of photodynamic therapy with verteporfin (PDT-V) in Caucasian patients with occult subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). METHODS The clinical records of consecutive patients with AMD-related occult CNV, treated with PDT-V for evidence of disease progression, were retrospectively examined. Eighty-four eligible subjects were subdivided into responders and nonresponders based on CNV responsiveness to the first PDT-V over a 3-month period. Six gene polymorphisms (i.e., factor V G1691A, prothrombin G20210A, factor XIII-A G185T, methylenetetrahydrofolate reductase C677T, methionine synthase A2756G, and methionine synthase reductase A66G) were genotyped in each patient. Logistic regression analyses were performed to explore the predictive role of phenotypic and genotypic variables for PDT-V effectiveness. RESULTS Regression models documented that PDT-V nonresponders were more frequently patients with the hyperfibrinolytic G185T mutation of factor XIII-A (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.11-0.73; P < 0.01). Univariate logistic regression was indicative of an overrepresentation of PDT-V responders among the combined carriers of thrombophilic factor V 1691A and prothrombin 20210A alleles (OR = 3.8; 95% CI: 0.94-15.6; P = 0.07). All the other predictors considered did not significantly influence the short-term CNV responsiveness to PDT-V. CONCLUSIONS These data provide evidence of the presence of a pharmacogenetic relationship between peculiar coagulation-balance genetic backgrounds and different levels of PDT-V effectiveness in patients with AMD with occult CNV.

Effectiveness of ranibizumab for neovascular age-related macular degeneration using clinician-determined retreatment strategy

Aims To report the effectiveness of intravitreal ranibizumab treatment for neovascular age-related macular degeneration in a tertiary centre. Methods 1 year prospective cohort study of patients with a diagnosis of neovascular age-related macular degeneration on fundus fluorescein angiography treated with ranibizumab. Patients received three consecutive monthly treatments, followed by a clinician-determined re-treatment strategy. Data collected included demographic details, baseline and subsequent follow-up visit measurements, refraction protocol best corrected visual acuity (BCVA), contrast sensitivity (CS) and central foveal thickness (CFT) on optical coherence tomography. Results 81 patients were included in the study. The mean age was 79.5 years with a male:female ratio 32:49. The mean number of treatments was 5.6±2.3. Visual outcomes at 12 months showed 17.1% gained ≥15 letters BCVA, 97.4% lost <15 letters and 2.5% lost ≥15 letters. Mean changes at 12 months were: BCVA +3.7±11.1 (p<0.01); CS +2.3±5.1 letters (p<0.001); CFT −100.1±111.9 μm (p<0.001). Conclusions Clinician-determined re-treatment after a three-dose initiation phase appears to be less effective in improving BCVA than in randomised controlled trials.

Incidence of neovascularization in the fellow eye of patients with unilateral retinal angiomatous proliferation.

AimsThe aim of this study is to describe the incidence and characteristics of neovascularization in the fellow eye of patients with retinal angiomatous proliferation (RAP).MethodsThis is a retrospective study conducted on all patients with a diagnosis of unilateral RAP commencing treatment in a single centre between November 2002 and January 2010. Clinical biomicroscopic examination, fluorescein angiography, and if required, indocyanine green angiography, and optical coherence tomography were used to evaluate all patients.ResultsIn all, 37 patients had a follow-up of ⩾1 year, 28 ⩾2 years, and 11 ⩾3. Patients who developed RAP in the fellow eye were: 2 of 37 (5.4%) within 1 year of follow-up, 4 of 28 (14.2%) within 2 years, and 4 of 11 (36.3%) within 3 years.ConclusionIn our case series, the risk of neovascularization in the fellow eye of patients with unilateral RAP increased with time. Approximately one-third of patients with a 3-year follow-up developed a bilateral disease. Our findings warrant further large-scale investigation.

12-month retrospective study and review of photodynamic therapy with verteporfin for subfoveal choroidal neovascularization in age-related macular degeneration.

Purpose: To evaluate the 12-month visual outcome of photodynamic therapy with verteporfin (PDT-V) for patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration and to verify the predictive role of visual and angiographic factors. Methods: This retrospective, interventional, consecutive case series study included subjects with different forms of subfoveal CNV. All patients received PDT-V according to Treatment of Age-Related Macular Degeneration With Photodynamic Therapy/Visudyne in Photodynamic Therapy guidelines. A review of medical and angiographic records was performed. Results: Two hundred sixteen patients were divided into 4 study groups: group I, 60 eyes with classic CNV; group II, 56 eyes with predominantly classic CNV; group III, 42 eyes with minimally classic CNV; and group IV, 58 eyes with occult CNV. In groups I and II, best-corrected visual acuity (BCVA) was moderately decreased, without reaching a statistically noticeable level during the entire follow-up; lesion size reduction only reached significance in group I. Groups III and IV showed evident worsening of BCVA (P < 0.05), despite concomitant reduction in CNV size (statistically remarkable only for occult CNV). All study groups exhibited a significant correlation between higher baseline BCVA and better final visual outcome. In groups II and IV, smaller baseline CNV sizes also favorably influenced final BCVA. Conclusions: Standardized PDT-V minimizes deterioration of central vision only in patients with classic and predominantly classic CNV. Irrespective of the CNV type, better BCVA at presentation represents a good predictive sign. In predominantly classic and occult lesions, minor initial CNV dimension is also a positive prognostic element.

Endogenous Aspergillus versicolor Endophthalmitis in an Immuno-competent HIV-positive Patient

A 25-year-old white, HIV-positive, immuno-competent man was referred to us because of a progressive blurred vision in his right eye. Clinical characteristics were suggestive for an unilateral fungal endophthalmitis, and thereby fluconazole firstly, followed by conventional amphotericin B were intravenously administered, without any significant improvement. Thus, a pars plana vitrectomy was performed. Aspergillus versicolor was isolated from the cultures of the vitreous sample and intravenous liposomal amphotericin B was administered. An increase of visual acuity together with a reduction of vitreous inflammation occurred. This case of ours represents the first report describing an endogenous endophthalmitis induced by Aspergillus versicolor.

Fundus Autofluorescence Patterns in Best Vitelliform Macular Dystrophy

PURPOSE To provide a systematic classification of fundus autofluorescence (FAF) patterns in patients affected by Best vitelliform macular dystrophy. DESIGN Cross-sectional prospective study. METHODS Patients affected by Best vitelliform macular dystrophy at different stages of the disease were prospectively enrolled from January 2012 to July 2013. Eighty eyes of 40 patients were included in the study. All patients underwent a complete ophthalmologic examination, including genetic characterization, short-wavelength FAF, and near-infrared FAF. Main outcome measures were the recognition of the FAF patterns in the different stages and the identification of a relationship between FAF patterns and best-corrected visual acuity (BCVA). RESULTS Six FAF patterns for both short-wavelength and near-infrared FAF were identified, including normal, hyper-autofluorescent, hypo-autofluorescent, patchy, multifocal, and spoke-like patterns. Applying Gasss classification for defining consecutive stages of Best vitelliform macular dystrophy (namely vitelliform, pseudohypopyon, vitelliruptive, atrophic, and cicatricial) identified no pattern as stage-specific. Patchy patterns had the highest prevalence. A statistically significant difference (Kruskal-Wallis ANOVA) was found among hyper-autofluorescent, patchy, and hypo-autofluorescent patterns, both in short-wavelength (P = .001) and near-infrared FAF (P = .001). Hyper-autofluorescent and hypo-autofluorescent patterns were associated with better and worse BCVA, respectively. CONCLUSIONS Six main patterns on both short-wavelength and near-infrared FAF were identified in Best vitelliform macular dystrophy. No FAF pattern can be considered stage-specific. Although a difference in the BCVA among the FAF patterns was registered, only a longitudinal study designed to evaluate the clinical and FAF modifications over the follow-up will help clarify the prognostic implications of each FAF pattern.

Topical and oral ketorolac administration increases the intraocular pressure-lowering effect of latanoprost.

Purpose: To verify the influence of a non-steroidal anti-inflammatory drug (NSAID), ketorolac (topical and oral) on the intraocular pressure reduction induced by 0.005% latanoprost topical administration, both in patients affected by primary open-angle glaucoma and in healthy controls. Methods: Two groups of subjects were enrolled for this randomized, prospective, masked clinical study: 16 glaucomatous patients well controlled with 0.005% latanoprost eyedrops (group I) and 16 healthy adult volunteers (group II). Group I subjects were treated at one-week intervals with 10 mg of oral ketorolac, oral placebo, topical ketorolac, and topical placebo, respectively; for each administration modality, the switch between drug and placebo was performed in a randomized, crossover, double-blind fashion. Group II subjects followed the same protocol, with the topical once-daily 0.005% latanoprost treatment starting three days prior to the ketorolac/placebo administration. Intraocular pressure (IOP) was investigated in both groups on the day of oral/topical administration of ketorolac or placebo at baseline (8:00 AM) and at the following intervals: 1, 2, 4, 8, 12, and 24 hours. Results: No significant IOP changes after oral and topical placebo administration were observed in either group. In contrast, when the subjects received ketorolac (either oral or topical), a marked decrease in IOP was recorded, with a noticeable fall at the first hour after the NSAID administration (p = 0.01), which remained still significant 8 hours later (p < 0.05). Conclusion: Topical and oral ketorolac strengthens the latanoprost-induced IOP-lowering effect both in glaucomatous patients and in healthy subjects.

Early multifocal electroretinogram findings during intravitreal ranibizumab treatment for neovascular age-related macular degeneration.

PURPOSE To evaluate changes in the multifocal electroretinogram (mfERG) in patients with neovascular age-related macular degeneration (nAMD) undergoing ranibizumab treatment. METHODS This was an observational, longitudinal, prospective study. Treatment-naive patients with nAMD who met the inclusion and exclusion criteria underwent a course of monthly injections of ranibizumab over 3 months. At baseline and month 3, each subject was evaluated with best corrected visual acuity (BCVA), contrast sensitivity (CS), fluorescein and indocyanine green angiography, optical coherence tomography (OCT), and mfERG. Additional mfERGs were performed at weeks 1 and 4 and BCVA and OCT at weeks 4 and 8. RESULTS Eighteen patients were enrolled. Between baseline and week 12, median BCVA improved from 59 to 69 ETDRS letters (P = 0.001), median CS improved from 29 to 30 letters (P = 0.05), mean OCT central foveal subfield thickness (CFT) decreased from 294 to 199 μm (P = 0.005), mean P1 amplitude density of the mfERG central zone increased from 35.85 to 51.55 nV/deg(2) (P = 0.009). The mfERG response correlated positively with BCVA (F = 22; P < 0.0001) and negatively with CFT (F = 12.73; P = 0.00078). CONCLUSIONS Intravitreal ranibizumab therapy appears to induce an increase in mfERGs centrally in patients with nAMD at least in the short term. Longer term studies to investigate the prognostic value of mfERG responses to predict changes in visual acuity in nAMD and other diseases are warranted. (ClinicalTrials.gov number, NCT01023971.).