Purpose To describe a new genetic variation of BEST1 gene in Best vitelliform macular dystrophy. Methods A patient with bilateral multiple retinal yellowish lesions at the posterior pole underwent fluorescein angiography, fundus autofluorescence, optical coherence tomography, electrooculogram and blood sample for genetic testing. Results A diagnosis of a Best vitelliform macular dystrophy was made. Heterozygous mutation c.76G > A (p.Gly26Ser) in exon 2 of the BEST1 gene was found. Conclusion These findings contribute to expand the mutation spectrum of BEST1 gene.

Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder characterized by motor, cognitive and psychiatric abnormalities. The onset of the disease is usually in the third-fourth decade of life, however 5–10% of subjects become symptomatic before 20 years ("juvenile Huntington's disease"). The disease is caused by an abnormal CAG repeat expansion in exon 1 of the "huntingtin" gene localized on the short arm of chromosome 4. This mutation leads to expression of the mutant huntingtin (mHtt) protein which forms toxic intracellular aggregates that are ubiquitously found in the central nervous system and peripheral tissues [ [1] Cisbani G. Cicchetti F. An in vitro perspective on the molecular mechanisms underlying mutant huntingtin protein toxicity. Cell Death Dis. 2012; 3e382 Crossref PubMed Scopus (51) Google Scholar ]. Although the main hallmark of the disease is represented by brain atrophy, several peripheral organs are considerably affected and their symptoms may, in fact, manifest before those resulting from brain pathology.

This review focuses on 5 new anti-VEGF drugs in the advanced stage of clinical development (i.e., phase 3): conbercept, brolucizumab, port delivery system with ranibizumab, abicipar pegol and faricimab. Results of clinical trials and the advantages of each drug compared to the available molecules are discussed in detail.

Retinal diseases affect an increasing number of patients worldwide because of the aging population. Request for diagnostic imaging in ophthalmology is ramping up, while the number of specialists keeps shrinking. Cutting-edge technology embedding artificial intelligence (AI) algorithms are thus advocated to help ophthalmologists perform their clinical tasks as well as to provide a source for the advancement of novel biomarkers. In particular, optical coherence tomography (OCT) evaluation of the retina can be augmented by algorithms based on machine learning and deep learning to early detect, qualitatively localize and quantitatively measure epi/intra/subretinal abnormalities or pathological features of macular or neural diseases. In this paper, we discuss the use of AI to facilitate efficacy and accuracy of retinal imaging in those diseases increasingly treated by intravitreal vascular endothelial growth factor (VEGF) inhibitors (i.e. anti-VEGF drugs), also including integration and interpretation features in the process. We review recent advances by AI in diabetic retinopathy, age-related macular degeneration, and retinopathy of prematurity that envision a potentially key role of highly automated systems in screening, early diagnosis, grading and individualized therapy. We discuss benefits and critical aspects of automating the evaluation of disease activity, recurrences, the timing of retreatment and therapeutically potential novel targets in ophthalmology. The impact of massive employment of AI to optimize clinical assistance and encourage tailored therapies for distinct patterns of retinal diseases is also discussed.

Retinal diseases affect an increasing number of patients worldwide because of the aging population. Request for diagnostic imaging in ophthalmology is ramping up, while the number of specialists keeps shrinking Cutting-edge technology embedding artificial intelligence (AI) algorithms are thus advocated to help ophthalmologists perform their clinical tasks as well as to provide a source for the advancement of novel biomarkers. In particular, optical coherence tomography (OCT) evaluation of the retina can be augmented by algorithms based on machine learning and deep learning to early detect, qualitatively localize and quantitatively measure epilintra/subretinal abnormalities or pathological features of macular or neural diseases. In this paper, we discuss the use of Al to facilitate efficacy and accuracy of retinal imaging in those diseases increasingly treated by intravitreal vascular endothelial growth factor (VEGF) inhibitors (i.e. anti-VEGF drugs), also including integration and interpretation features in the process. We review recent advances by Al in diabetic retinopathy, age -related macular degeneration, and retinopathy of prematurity that envision a potentially key role of highly automated systems in screening, early diagnosis, grading and individualized therapy. We discuss benefits and critical aspects of automating the evaluation of disease activity, recurrences, the timing of re treatment and therapeutically potential novel targets in ophthalmology. The impact of massive employment of AI to optimize clinical assistance and encourage tailored therapies for distinct patterns of retinal diseases is also discussed.

Only a few genes involved in teeth development and morphology are known to be responsible for tooth abnormalities in Mendelian-inherited diseases. We studied an inbred family of Pakistani origin in which two first-cousin born brothers are affected by early tooth loss with peculiar teeth abnormalities characterized by the absence of cementum formation. Whole exome sequencing revealed a H2665L homozygous sequence variant in the VCAN gene. Dominant splicing mutations in VCAN are known to cause Wagner syndrome or vitreoretinopathy. We explored teeth morphology in these two patients, while versican expression was assessed by western blot analysis. Early signs of vitreoretinopathy were found in the elder brother while the parents were completely negative. Our findings suggest that the homozygous recessive H2665L missense sequence variant impairs the normal morphology of the teeth roots via loss of cementum synthesis, and is also associated with early onset, recessive, Wagner syndrome, thus expanding both the phenotype mutation scenario and the inheritance mode of VCAN mutations.

PURPOSE:To evaluate the incidence of pseudophakic cystoid macular edema (PCMO) in patients treated with corticosteroids alone or in combination with bromfenac or nepafenac eyedrops after uneventful cataract surgery. MATERIALS AND METHODS:Prospective, randomized, open-label, placebo-controlled clinical trial. Patients who underwent routine cataract surgery with intraocular lens (IOL) implant were randomly divided into three groups receiving either bromfenac or nepafenac in association with dexamethasone or dexamethasone alone (control group) postoperatively. Best-corrected visual acuity (BCVA) measurement, slit lamp and fundus examination and optical coherence tomography (OCT) were performed preoperatively, 1 and 5 weeks after surgery. Primary outcome was defined as patients (%) in whom macular edema developed within 5 weeks after cataract surgery; secondary end points were patients (%) with BCVA improvement from pre-op through 5 weeks after surgery and corneal toxicity. RESULTS:A total of 144 patients completed the study, 48 for each group. In all groups, mean central subfield thickness at OCT increased significantly 5 weeks after surgery (p < 0.01). However, at this time point, four patients (8.3%) of the control group and none in nepafenac and bromfenac groups developed PCMO (p = 0.016). Compared with baseline, mean BCVA significantly improved both at 1 and 5 weeks in all groups (p < 0.01). At 1 week, the nepafenac group showed a mean BCVA significantly lower compared with both the control (p = 0.038) and bromfenac group (p = 0.002). CONCLUSIONS:Co-administration of nepafenac or bromfenac and steroids in patients who underwent routine cataract surgery is associated with a lower incidence of PCMO compared with steroid monotherapy.

Retinal vein occlusion (RVO) is the second most common cause of visual loss in the Western World. RVO is usually classified into branch RVO (BRVO) and central RVO (CRVO) according to the anatomical site of the vascular occlusion. The pathogenesis of RVO is not yet fully understood, however an important event is the intraluminal thrombus formation, which is usually secondary to several conditions such as hypertension, hyperlipidemia, diabetes and thrombophilia. The blockage of venous circulation causes an elevation of intraluminal pressure in the capillaries, leading to hemorrhages and leakage of fluid within the retina, increase of interstitial pressure and a consequent reduction of retinal perfusion. Ischemia may develop resulting in secretion of vascular endothelial growth factor (VEGF) that causes further vascular leakage and retinal oedema. VEGF has therefore a leading role in RVO pathogenesis and symptoms. As a consequence use of anti-VEGF agents by intravitreal injections has become very common with the aim to improve the clinical outcomes in these patients. Currently 2 anti-VEGF agents (ranimizumab and aflibercept) have been FDA (Food and Drug Administration) and EMA (European Medicine Agency) approved for the treatment of RVO, while another VEGF inhibitor (bevacizumab) is often used "off-label" in clinical practice. Many treatment regimens have been suggested in the clinical trials with these drugs, as monthly injections or injections when needed, however the ideal regimen has not been defined yet. We conducted a systematic review searching MEDLINE for the following terms: retinal vein occlusion, ranibizumab, bevacizumab, aflibercept, vascular endothelial growth factor, macular oedema. Data were extracted by one author (AG and BE) and checked by a second (BPM, CC). Aim of this article was to review available data for each drug, focusing on their efficacy and safety trying to compare their advantages and limits.

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 Gass's 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.

PURPOSE: To evaluate a new computerized segmentation technique for the quantification of intraretinal and subretinal fluid in spectral-domain optical coherence tomography (SD OCT) images of the retina.DESIGN: Prospective, cross-sectional study.METHODS: Thirty-seven B-scan images of 37 patients with exudative age-related macular degeneration were chosen randomly from SD OCT volume scans (1 per volume scan). All hyporeflective areas in the image first were segmented automatically as candidate regions by the program. Researchers who were masked to the candidate region information selected each fluid region from the original image using a single mouse click. The program then delineated the boundary of each region selected and calculated quantitative parameters, including total area of fluid regions if multiple regions were selected. The performance of our technique was validated by comparing the results with the measurements obtained from boundaries manually delineated by 2 masked observers. Time efficiency, agreement with manual delineation, and intraobserver and interobserver agreement of using the program were evaluated.RESULTS: The proposed technique reduced the average processing time per image approximately 6-fold (15 seconds for computerized segmentation vs 90 seconds for manual delineation). There was good agreement between computerized segmentation and manual delineation measured by intraclass correlation coefficient (range, 0.897 to 0.979) and the Dice coefficient (range, 0.721 to 0.785). The proposed technique has excellent intraobserver and interobserver agreement (intraclass correlation coefficient range, 0.998 to 0.999; Dice coefficient range. 0.959 to 0.981).CONCLUSIONS: This computerized segmentation method allows for accurate and fast quantification of fluid in retinal SD OCT images and could assist in monitoring disease progression and evaluating therapeutic intervention. (Am J Ophthalmol 2013;155:277-286. (c) 2013 by Elsevier Inc. All rights reserved.)

The anterior chamber angle is the actual anatomical angle created by the root of the iris and the peripheral corneal vault. Within it lie the structures involved in the outflow passage of the aqueous, namely the trabecular meshwork and the Schlemm’s canal (figure 1). The depth of the angle in a healthy eye is approximately 30°, with the superior part usually less deep than the inferior half. However the depth is influenced by gender, age and refractive error. Female gender has the greatest influence on iridocorneal angle reduction, followed by age and spherical equivalent (Rufer et al.). The relationship of the iris plane to the cornea has a significant effect on the aqueous humor’s accessibility to its outflow drainage system. In eyes where the iris and corneal endothelium are “closed”against one another, the aqueous will not be drained causing an increase of the intraocular pressure (angle closure glaucoma) (Lens, 2008).

Age-related macular degeneration (AMD) is the leading cause of blindness among elderly patients in developed countries. Although the pathogenesis of AMD is still largely unknown, it is now well known that vascular endothelial growth factor (VEGF) plays a pivotal role in the growth of the abnormal blood vessels (i.e. choroidal neovascularization, CNV) which characterizes the "wet form" of this ocular disease. Therefore, inhibiting VEGF has turned out to be a good way of more effectively controlling neovascular AMD. VEGF is a heparin-binding glycoprotein with potent angiogenic, mitogenic and vascular permeability-enhancing activities specific for endothelial cells. Currently two anti-VEGF compounds have been approved by the US Food and Drug Administration (FDA) for the treatment of neovascular AMD: pegaptanib and ranibizumab. Off-label usage of bevacizumab, an anti-VEGF agent similar to ranibizumab, has also become fairly common. The substantial improvement of visual acuity noticed in patients treated with ranibizumab has made this drug the gold standard for AMD therapy. However, as with many new therapies, there are unresolved issues, including safety, cost, and dosing frequency.This review describes in details the properties and efficacy of the three anti-VEGF agents in use in clinical practice. Promising emerging anti-VEGF strategies (VEGF-trap, small interfering RNA, tyrosine kinase inhibitors) which aim to improve outcomes, safety and treatment burden through novel mechanisms of action are also discussed.