A hypothetical therapeutic effect of light peripheral panretinal photocoagulation in neovascular age-related macular degeneration

Background: Vascular endothelial growth factor (VEGF) is a significant modulator of ocular angiogenesis, including that of neovascular age-related macular degeneration (nAMD). Intravitreal injection of anti-VEGF is the benchmark treatment for most retinal vascular diseases, including nAMD, diabetic maculopathy, and macular edema secondary to retinal venous occlusion. Anti-VEGF treatment is a high-frequency, time-consuming, non-cost-effective therapy, especially in countries and regions with limited resources. This treatment is easily restricted, and in practice, maintaining long-term periodic care is challenging for patients. Hypothesis: Light peripheral panretinal photocoagulation (PPRP) is applied in a mild form (barely visible mild light gray mark) anterior to the equator so as not to jeopardize the visual field. PPRP lessens the ischemia that causes neovascularization and decreases the metabolic demand in the peripheral retina. PPRP reduces serum angiopoietin-2 and VEGF levels in patients with type 2 diabetes mellitus with proliferative diabetic retinopathy. We propose using light PPRP to suppress VEGF secretion, aiming to attenuate the VEGF drive and halt choroidal neovascular growth in eyes with nAMD. Our regimen is based on two concepts: first, nAMD is a diffuse or generalized disease that affects the posterior segment; and second, PPRP is very effective in regressing diabetic retinopathy. PPRP has reportedly been successful in cases of macular edema (diabetic or following venous occlusion) resistant to VEGF antagonists. Light PPRP may be used as prophylaxis, adjunctive treatment, or monotherapy in nAMD when intravitreal injections of VEGF antagonists are not feasible. Conclusions: The established light PPRP therapy could be promising as a one-time, cost-effective therapy or prophylaxis in patients with nAMD or at high risk. This proposed modality could be suitable for patients who have injection phobia or prefer a one-time affordable therapy to the long-term monthly visits to retinologists. Future trials are necessary to verify the safety and efficacy of this proposed treatment modality in selected patients with nAMD

Fluorescein Leakage and Optical Coherence Tomography Features of Choroidal Neovascularization Secondary to Pathologic Myopia

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Practical Management of Retinal Vein Occlusions

Retinal vein occlusion (RVO) is the second most common cause of visual impairment due to retinal disease after diabetic retinopathy. Nowadays, the introduction of new, powerful diagnostic tools, such as spectral domain optical coherence tomography, and the widespread diffusion of intravitreal drugs, such as vascular endothelial grow factor inhibitors or implantable steroids, have dramatically changed the management and prognosis of RVO. The authors aim to summarize and review the main clinical, diagnostic, and therapeutic aspects of this condition. The authors conducted a review of the most relevant clinical trials and observational studies published within the last 30 years using a keyword search of MEDLINE, EMBASE, Current Contents, and Cochrane Library. Furthermore, for all treatments discussed, the level of evidence supporting its use, as per the US Preventive Task Force Ranking System, is provided

Evidence for Anti-vascular Endothelial Growth Factor Treatment of Diabetic Macular Oedema

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Ranibizumab in the treatment of patients with visual impairment due to diabetic macular edema

Diabetic macular edema is the major cause of visual acuity impairment in diabetic patients. The exact etiopathogenesis is unknown and, currently, grid/focal retinal laser photocoagulation represents the recommended treatment. It has been demonstrated that vascular endothelial growth factor (VEGF) plays a key role in the pathogenesis of diabetic macular edema by mediating vascular permeability and accumulation of intracellular and extracellular fluid, and thereby represents an appealing candidate as a therapeutic target for the treatment of diabetic macular edema. The advent of intravitreal anti-VEGF drugs has opened up a new era for the management of diabetic macular edema. At present, three anti-VEGF substances are available for routine clinical use, ie, pegaptanib, ranibizumab, and bevacizumab. The aim of this review is to summarize the evidence supporting the use of ranibizumab in clinical practice. Most of the studies analyzed in this review are prospective, controlled clinical trials that have focused on documenting the therapeutic effect of ranibizumab and its safety, providing encouraging results

Identifying missing pieces in color vision defects: a genome-wide association study in Silk Road populations

Introduction: Color vision defects (CVDs) are conditions characterized by the alteration of normal trichromatic vision. CVDs can arise as the result of alterations in three genes (OPN1LW, OPN1MW, OPN1SW) or as a combination of genetic predisposition and environmental factors. To date, apart from Mendelian CVDs forms, nothing is known about multifactorial CVDs forms. Materials and Methods: Five hundred and twenty individuals from Silk Road isolated communities were genotyped and phenotypically characterized for CVDs using the Farnsworth D-15 color test. The CVDs traits Deutan-Protan (DP) and Tritan (TR) were analysed. Genome Wide Association Study for both traits was performed, and results were corrected with a False Discovery Rate linkage-based approach (FDR-p). Gene expression of final candidates was investigated using a published human eye dataset, and pathway analysis was performed. Results: Concerning DP, three genes: PIWIL4 (FDR-p: 9.01*10-9), MBD2 (FDR-p: 4.97*10-8) and NTN1 (FDR-p: 4.98*10-8), stood out as promising candidates. PIWIL4 is involved in the preservation of Retinal Pigmented Epithelium (RPE) homeostasis while MBD2 and NTN1 are both involved in visual signal transmission. With regards to TR, four genes: VPS54 (FDR-p: 4.09*10-9), IQGAP (FDR-p: 6,52*10-10), NMB (FDR-p: 8.34*10-11), and MC5R (FDR-p: 2.10*10-8), were considered promising candidates. VPS54 is reported to be associated with Retinitis pigmentosa; IQGAP1 is reported to regulate choroidal vascularization in Age-Related Macular Degeneration; NMB is involved in RPE homeostasis regulation; MC5R is reported to regulate lacrimal gland function. Discussion: Overall, these results provide novel insights regarding a complex phenotype (i.e., CVDs) in an underrepresented population such as Silk Road isolated communities

Extrafoveal Müller cells detection in vivo in the human retina: A pilot study based on optical coherence tomography.

Abstract Muller cells (MC) represent a key element for the metabolic and functional regulation of the vertebrate retina. The aim of the present study was to test the feasibility of a new method for the in-vivo detection and quantification of extrafoveal MC in human retina. We developed a new approach to isolate and analyse extrafoveal MC in vivo, starting from structural optical coherence tomography data. Our pilot investigation was based on the optical properties of MC, which are known to not interfere with the light reaching the outer retinal structures. We reconstructed MC in the macular region of 18 healthy subjects and the quantitative analyses revealed ~42,000/9 mm2 cells detected. Furthermore, we included 2 patients affected by peripheral intraocular melanoma, with macular sparing, needing surgical enucleation. We used these two eyes to perform a qualitative comparison between our reconstructions and histological findings. Our study represents the first pilot investigation dedicated on the non-invasive isolation and quantification of MC, in-vivo, in human retina. Although we are aware that our study has several limitations, first of all related with the proper detection of foveal MC, because of the peculiar z-shape morphology, this approach may open new opportunities for the non-invasive in vivo analysis of MC, providing also potential useful perspectives in retinal diseases

New OCT and OCTA Insights in Inherited Retinal Dystrophies

Optical coherence tomography (OCT) and OCT angiography (OCTA) radically changed the diagnostics of inherited retinal dystrophies (IRD), providing new information regarding the microstructural changes occurring in each disease. The introduction of quantitative metrics provided even more steps forward in the understanding of IRD pathogenesis and course, allowing to propose new ways to categorize different subgroups of patients, characterized by remarkably different characteristics and prognosis. All these informations provided insights regarding how heterogeneous the clinical spectrum of IRD is. In the present study, we provide an updated description of OCT and OCTA findings in the main IRD, including retinitis pigmentosa, Stargardt disease, and Best vitelliform macular dystrophy. Moreover, we discuss imaging findings in pigmented paravenous retinochoroidal atrophy, a rare condition that is undergoing even growing scientific and clinical interest. In addition, we provided a brief updated scenario on imaging findings in pattern dystrophies. We discuss in detail the current state-of-the-art and the new insights provided by quantitative OCT and OCTA approaches, offering a complete description that might be helpful both for expert and nonexpert researchers interested in IRD

Quark Dipole Operators in Extended Technicolor Models

We study diagonal and transition quark dipole operators in a class of extended technicolor (ETC) models, taking account of the multiscale nature of the ETC gauge symmetry breaking and of the mixing among ETC interaction eigenstates. Because of this mixing, terms involving the lowest ETC scale can play an important role in dipole operators, and we focus on these terms. We derive from experiment new correlated constraints on the quark mixing angles and phases. Our bounds yield information on mixing angles individually in the up- and down-sectors, for both left- and right-handed quark fields and thus constrain even quark mixing parameters that do not enter in the CKM matrix. With phases of order unity, we conclude that these mixing angles are small, constraining future ETC model building, but plausibly in the range suggested by the size of the CKM elements. These values still allow substantial deviations from the standard model predictions, in particular for several CP violating quantities, including the asymmetries in $b \to s \gamma$ and $B_{d} \to \phi K_S$, $Re(\epsilon^\prime/\epsilon)$, and the electric dipole moments of the neutron and the ${}^{199}$Hg atom.Comment: 9 pages, late

LIGHTSITE II Randomized Multicenter Trial: Evaluation of Multiwavelength Photobiomodulation in Non-exudative Age-Related Macular Degeneration.

INTRODUCTION Photobiomodulation (PBM) represents a potential treatment for non-exudative age-related macular degeneration (AMD). PBM uses wavelengths of light to target components of the mitochondrial respiratory chain to improve cellular bioenergetic outputs. The aim of this study was to further investigate the effects of PBM on clinical, quality of life (QoL) and anatomical outcomes in subjects with intermediate stage non-exudative AMD. METHODS The multicenter LIGHTSITE II study was a randomized clinical trial evaluating safety and efficacy of PBM in intermediate non-exudative AMD. The LumiThera Valeda® Light Delivery System delivered multiwavelength PBM (590, 660 and 850 nm) or sham treatment 3 × per week over 3-4 weeks (9 treatments per series) with repeated treatments at baseline (BL), 4 and 8 months. Subjects were enrolled with 20/32 to 20/100 best-corrected visual acuity (BCVA) and no central geographic atrophy (GA) within the central fovea (500 μm). RESULTS LIGHTSITE II enrolled 44 non-exudative AMD subjects (53 eyes). PBM-treated eyes showed statistically significant improvement in BCVA at 9 months (n = 32 eyes, p = 0.02) with a 4-letter gain in the PBM-treated group versus a 0.5-letter gain in the sham-treated group (ns, p < 0.1) for patients that received all 27 PBM treatments (n = 29 eyes). Approximately 35.3% of PBM-treated eyes showed ≥ 5-letter improvement at 9 months. Macular drusen volume was not increased over time in the PBM-treated group but did show increases in the sham-treated group. While PBM and sham groups both showed GA lesion growth in the trial period, there was 20% less growth in the PBM group over 10 months, suggesting potential disease-modifying effects. No safety concerns or signs of phototoxicity were observed. CONCLUSION These results confirm previous clinical testing of multiwavelength PBM and support treatment with Valeda as a novel therapy with a unique mechanism of action as a potential treatment for non-exudative AMD. TRIAL REGISTRATION Clinicaltrial.Gov Registration Identifier: NCT03878420