Choroidal Neovascularization Industry

In this research study, to investigate teratogenic effect of intravitreal injection of bevacizumab in pregnant rat model, twenty seven female Wistar rats were inseminated. Pregnant rats were divided into 6 groups (three groups as case and three as control groups). Each case and control groups were divided according to the day of intravitreal injections (day 2, 10 and 18). Rats in the case groups received 4 µL intravitreal injection of bevacizumab and the control groups received the same volume of distilled water. The tail and umbilical cord length in case groups 1, 2, and 3 did not display any significant differences compared to their control groups. The fetal weight was significantly lower in the case groups 1 (p>0.001) and 2 (p>0.001) compared to their control groups. Furthermore, the placental weight was only lower in the case group 1 (p>0.001). Case group 2 had a shorter crown rump length in comparison with its control group (p=0.029). Morphological investigations showed two abnormal cases of gastroschisis in group 1 and a case of a cleft in the skull in one of the rats in case group 2. The results show that intravitreal bevacizumab has developmental effect when administered in the early stages of pregnancy; but it is safe when administered in the last week of pregnancy in rats.

Ocular histoplasmosis (OHS) is a potential cause of advanced vision loss in the United States, especially in endemic areas including the OhioeMississippi River Valley. Most patients are symptomatic, exhibiting peripapillary and peripheral chorioretinal scars and macular pigmentary changes. Some, however, develop vision loss owing to choroidal neovascularization (CNV) of the macula, associated with subretinal bleeding, intraretinal and subretinal fluids, and fibrosis in advanced cases. Although the pathogenesis of CNV in OHS syndrome is incompletely understood, there have been advances in our understanding of risk factors for CNV in age-related macular degeneration (AMD). An increased prevalence of single nucleotide polymorphisms in complement factor H (CFH), complement component 3 (C3), mitochondrially-encoded NADH dehydrogenase 2 (MT-NDH2), and age-related maculopathy susceptibility 2 (ARMS2) have been associated with CNV in AMD. Clarifying the mechanisms responsible for CNV onset and progression in OHS is critical for developing treatments to prevent CNV in patients with OHS. This prospective study tested the hypothesis that risk alleles in CFH, C3, MT-NDH2, and ARMS2 genes for AMD would be associated with CNV associated with OHS. All patients completed and signed an informed consent for this study that was compliant with the Health Insurance Portability and Accountability Act of 1996 and approved by the institutional review board. Inclusion criteria were characteristics classic for OHS with or without CNV. Exclusion criteria included the presence of other potentially confounding retinovascular disease. Physicians completed a data collection form at the screening visit. Demographic data including age, gender, and past ocular history were noted. Examination findings at the enrollment visit were documented. Smoking history was recorded, defined as "current," "former," or "never." Buccal mucosal swab samples were obtained with sterile cotton tip applicators. The samples were placed in a sealed biohazard bag and mailed to Macula Risk (ArcticDx Bonita Springs, FL) for analysis. Analysis of target genes was performed as previously described. Ninety-three patients were enrolled. Sixty-two had CNV associated with OHS (OHS-CNV group) and 31 patients had classic features of OHS without evidence of current or prior CNV (OHScontrol group). There was a significant difference in age between the 2 groups (P ¼ 0.0290; Table ; available at www.aaojournal.org). There was a greater proportion of males in the OHS-CNV group versus OHS-control; however, this was not significant (P ¼ 0.1099; Table ). Patients in the OHS-CNV group had higher rates of past and/or current smoking versus the OHScontrol subjects (62.9% for OHS-CNV vs 48.3% OHS-control; P ¼ 0.001). The results of the genetic analysis for ARMS2, C3, MT-NDH2, and CFH in OHS-CNV and OHS-control subjects are shown in

PURPOSE. Age-related macular degeneration (AMD), with its complex traits and multiple risk factors, is the leading cause of blindness in the elderly. A strong association between a coding variant, Y402H, in the complement factor H gene (CFH) and AMD has been recently identified in white patients. This study was conducted to investigate the association between the Y402H polymorphism in CFH and neovascular AMD in Chinese patients. METHODS. One hundred sixty-three Chinese patients with neovascular AMD and 232 age-matched healthy controls were enrolled in the study. Genomic DNA from white blood cells was extracted. The Y402H polymorphism in CFH, with the substitution of T to C at nucleotide position 1277 in exon 9, was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. The association between the genetic polymorphism and the disease was examined by 2 test and logistic regression. RESULTS. The frequency of the risk allele, 1277C, was 11.3% in AMD patients compared with 2.8% in controls (P Ͻ 0.00001). Genotype frequency differed significantly between the two groups (1277TT 81.0%, 1277TC 15.3%, and 1277CC 3.7% in the AMD group; 1277TT 94.4%, 1277TC 5.6%, and 1277CC 0% in the control group; P Ͻ 0.0001). The 1277C allele significantly increased the risk for neovascular AMD and had an odds ratio of 4.4 (95% confidence interval [95% CI], 2.3-8.5; P Ͻ 0.00001). CONCLUSIONS. The allele frequency of Y402H polymorphism in CFH has an ethnic variation, with much lower 1277C frequency in Chinese than in white patients. Despite this, the polymorphism is significantly associated with neovascular AMD in the Chinese population.

To evaluate the feasibility, efficacy, and selectivity of photodynamic therapy (PDT) using targeted delivery of verteporfin to choroidal neovascularization (CNV) in the rat laser-injury model of CNV. Methods: We performed PDT in rat eyes on experimental CNV and normal retina and choroid using verteporfin conjugates. A targeted verteporfin conjugate was made by conjugating verteporfin (after isolation from its liposomal formulation) to a modified polyvinyl alcohol (PVA) polymer (verteporfin-PVA) followed by linkage to the peptide ATWLPPR known to bind the receptor for vascular endothelial growth factor, VEGFR2. The verteporfin-PVA conjugate served as a control. We performed fluorescent fundus angiography to determine the optimal timing of light application for PDT using the conjugates. Closure of CNV was assessed angiographically and graded in a masked standardized fashion. We used standardized histological grading to compare the effects on normal retina and choroid. Results: The verteporfin-PVA conjugation ratio was on average 28:1. The conjugate retained typical emission/ excitation spectra and photosensitizing activity and was as efficient as an equivalent amount of verteporfin. Peak intensity of targeted verteporfin in CNV was detected angiographically at 1 hour after intravenous injection. Photodynamic therapy using targeted verteporfin (3 or 4.5 mg/m 2) with light application 1 hour after drug injection showed angiographic closure of all treated CNV (17/17) 1 day af

Purpose: The rainbow smelt (Osmerus mordax), is a teleost fish, which avoids freezing by becoming virtually isosmotic with seawater. The effects that such massive changes in osmolarity have on both its visual system and its highly evolved and specialized circulation are not known. New knowledge about the osmotic adaptation of the rainbow smelt eye is highly relevant to the adaptation and survival of this species and to its ability to feed as a visual predator in the face of environmental pressures. Moreover, the molecular physiologic response of the smelt to osmotic stress might provide valuable insights into understanding and managing mammalian pathological hyperosmolarity conditions, such as diabetes. We undertook the present study to provide an initial assessment of gene expression in ocular vasculature during osmotic adaptation in rainbow smelt. Methods: Immunohistochemistry with species cross reactive antibodies was used to assess blood vessel protein expression in paraffin sections. Western blotting was used to further verify antibody specificity for orthologs of mammalian blood vessel proteins in rainbow smelt. Thermal hysteresis and the analysis of glycerol concentrations in vitreous fluid were used to assess the physiologic adaptive properties of cold stressed eyes. Results: Glycerol levels and osmotic pressure were significantly increased in the vitreal fluid of smelt maintained at <0.5 °C versus those maintained at 8-10 °C. Compared to the 8-10 °C adapted specimens, the rete mirabile blood vessels and connecting regions of the endothelial linings of the choroidal vessels of the <0.5 °C adapted specimens showed a higher expression level of Tubedown (Tbdn) protein, a marker of the endothelial transcellular permeability pathway. Expression of the zonula occludens protein ZO-1, a marker of the endothelial paracellular permeability pathway showed a reciprocal expression pattern and was downregulated in rete mirabile blood vessels and connecting regions in the endothelial linings of choroidal vessels in <0.5 °C adapted specimens. Smelt orthologs of the mammalian Tbdn and zoluna occludens protein 1 (ZO-1) proteins were also detected by western blotting using anti-mammalian antibodies raised against the same epitopes as those used for immunohistochemistry. Conclusions: This work provides the first evidence that molecules known to play a role in ocular vascular homeostasis are expressed and may be differentially regulated during anti-freezing cold adaptation in smelt eyes. We propose a hypothesis that in a state of cold-induced hyperosmolarity, changes in ZO-1 expression are associated with the passage of small solutes from the plasma space to ocular fluid, while changes in Tbdn expression regulate the passage of proteins between the ocular fluid and plasma space. This work also provides fundamental insight into the mechanisms underlying the adaptation of the blood-retinal barrier to metabolically relevant compounds such as glycerol.

PURPOSE. To determine the efficacy of Tookad (WST09; Negma-Lerads, Magny-Les-Hameaux, France) photodynamic therapy (T-PDT) by evaluating the angiographic and histologic closure of choroidal vessels at different radiance exposures, drug dosages, and intervals between photosensitizer injection and laser application in a rabbit model. METHODS. Chinchilla Bastard rabbits were injected intravenously with three different dye concentrations (2.5, 5, and 10 mg/kg) before application of light. In every group T-PDT was performed at four different times after injection: 5, 15, 30, and 60 minutes with different radiance exposures ranging from 200 to 3 J/cm 2. Fundus photographs and fluorescein angiograms were obtained 90 minutes after injection. Follow-up angiographies were performed at days 1, 3, 7, and 14 after initial treatment. Histology was performed in selected cases immediately after treatment and on days 1, 3, and 7. RESULTS. Immediately after irradiation, most of the visible lesions were angiographically hyperfluorescent due to damaged vessel endothelium and associated RPE damage. Lesions from high-radiance exposures revealed immediate hypofluorescence, indicating vessel closure. Hypofluorescent lesions appeared mainly during day 1 (all lesions angiographically visible, some hypofluorescent) to day 3 (all lesions hypofluorescent) after treatment. At day 7, ophthalmoscopically visible hyperpigmentation took place in all lesions. ED 50 thresholds for angiographic hypofluorescence determined at day 3 after treatment with 2.5 mg/kg were 18.8 J/cm 2 (5 minutes), 62.0 J/cm 2 (15 minutes), and Ͼ100 J/cm 2 (30 minutes); with 5 mg/kg, 8.4 J/cm 2 (5 minutes), 22.8 J/cm 2 (15 minutes), 54.5 J/cm 2 (30 minutes), and Ͼ100 J/cm 2 (60 minutes); and with 10 mg/kg, 11.7 J/cm 2 (30 minutes) and 54.1 J/cm 2 (60 minutes). Histology of the angiographically hypofluorescent lesions revealed vessel thrombosis in all groups 1 hour after PDT up to 7 days after treatment. Sparing of photoreceptors indicated selectivity of T-PDT; however, slight damage was partly observable. After 7 days, localized proliferation of the RPE cells was noted and was enhanced 14 days after treatment. CONCLUSIONS. T-PDT has the potential to achieve selective choroidal vessel occlusion with proper parameter selection, such

Aim: To know clinical profile of non AMD CNVM in context to (Type, location, FFA , OCT characteristics Demography, incidence, causes) To know clinical response to Anti-VEGF, conventional or PRN Result:-Type:-14(30.4%) Myopic cnvm, 11(23.9%) Idiopathic cnvm, 9(19.5%) PFT, 4(8.7%) Inflammatory, 3(6.5%), choroidal osteoma with cnvm, 2(4.3%) Angiod streak, 2(4.3%) CSR with cnvm, 1(2.2%) Traumatic cnvm. Location:-Extrafoveal (2), juxta foveal (14), Sub foveal (27), Peripapillary (1) (Angiod streak), Unifocal (42), multifocal (3) (PFT) FFA:-39(84.7%) classic, 4(8.7%) Occult cnvm, 3(6.5%) were undifferentiated. CT:-21(45.6%) type-2 membrane, 9(19.5%) undifferentiated, 2(4.4%) type-1 membrane Demography:-Average age 49.6 yrs,range (20-64 yrs);Male preponderance, M:F ratio is 1.3:1,Almost all had unilateral presentation except PFT (parafoveal telangiectasias) and myopic CNVM which bilateral. Interpretation:-6 cases responded to single dose. 10 responded to second dose of anti VEGF and 21 responded to 3rd dose. 9 were not responders to 3 dosages, given option of PDT with anti-VEGF. 2 cases responded to PDT. 1 case responded to high dose steroids with anti-Koch's in inflammatory CNVM. 4 cases remain non responded to treatment. 31(67%) had improvement in vision, 8(18%) had stable vision, while 7(15%) had deteriorated. Conclusion:-Myopic CNVM cases showed 100% response after 1 to 3 dosages of anti-VEGF.Non-AMD cnvm cases respond well to anti VEGF alone, few more respond to added PDT.Inflammatory CNVM require high dose steroid

Background: Age related macular degeneration (ARMD ) is the major cause of severe visual loss in older adults.Different treatment modalities are available such as: Laser photocoagulation,photodynamic therapy,transpupillary thermotherapy,submacular surgery & anti-vegf.

Aims & Objectives: The aim of our study was to evaluate the efficacy and safety of intravitreally administered Bevacizumab a humanized monoclonal anti –VEGF in Neovascular Age related Macular Degeneration.

Methodology: This non randomized, prospective study was carried out on 75 eyes of 75 patients attending the OPD at M & J Institute Of Ophthalmology and diagnosed as having Neovascular ARMD confirmed on FFA and SD-OCT . After taking written informed consent all patients were injected with intravitreal Bevacizumab 1.25 mg/0.05 ml. Follow up visits were scheduled one week, one month postprocedure and every monthly thereafter.

Results: 75 eyes of 75 patients were included in this non randomized prospective study. & 29.33% patients required 2 injections. Visual acuity is improved more than 3 lines from baseline in 21.33% patient, 64% patient have 2-3 lines gain & 6.66% patients showed 0-1 line gain in snellen’s visual acuity. 5.33% patients have a loss of 1 line from baseline & 2.66% patients showed loss of 2-3 lines. Central foveal thickness decreased more than 200 microns from baseline in 52% patients, 28% patients have decreased of 100-200 microns & 20% patients have decreased of less than 100 microns.

Discussion: Approximately 10 % of ARMD patients manifest the neovascular form of the disease. 12 weeks). Our study showed that 80% patients had decrease in central foveal thickness more than 100 microns from baseline at the end of one year. 85% patients had gain of 2 or more lines on Snellen’s visual acuity chart from baseline.No patient had any serious local or systemic adverse reactions.Limitations of our study is small number of patients,ICG not done,not compared with other anti-vegf drugs.

Conclusion: Intravitreal Bevacizumab is a safe and effective drug in treatment of neovascular age related macular degeneration without any serious systemic or local adverse effects

Due to differences in eye anatomy, local variation in image blur can be a problem in widefield fundus images. This forms a spatially varying defocus estimation problem that has recently been addressed using multi-scale deep learning (DL) methods for blind motion deblurring. This study aims to characterize the performance of a DL network to improve vessel sharpness in fluorescein angiograms.  Processed images were graded as the same or better in overall image sharpness in 90.2% of images, in retina appearance in 82.9% of images, and in choroid appearance in 97.6% of images.  In 8 cases, the processed image was graded as worse. In these cases, a more detailed analysis was done. In 6 cases, small vascular details were removed.  In 1 case, perivascular dye leakage appeared sharpened. In another, the vessel-like structures were generated in an area with no blood vessels. PURPOSE RESULTS

cases underwent trabeculectomy after vitrectomy, there were no complications, such as the collapse of eye, caused by a vitreous condition. Visual prognosis is usually benign after the resolution of haemorrhages; however, cases with poor visual acuity as shown in case 2 have also been described. Taken together, because clinical features in glaucoma secondary to FAP are related to the pathogenesis of this rare complication after trabeculectomy, early postoperative hypotony should be avoided to prevent it.

While those with neovascular age-related macular degeneration (NV-AMD) may be at increased risk of injurious falls risk due to poor central vision and suboptimal responses when falling, preserved peripheral vision and decreased activity levels may actually be protective. Compared with control participants, patients with NV-AMD had a significantly greater number of falls and almost twice the risk of injurious falls.

Objective: The VEGF function blockage effectively reduces the progression of diabetic retinopathy. Ranibizumab and bevacizumab are some anti-VEGF monoclonal antibodies (mAb). Considering the importance of affinity maturation of ranibizumab, we aimed to find the essential amino acids of the ranibizumab antibody (Ab). Materials and Methods: We tried to find the important amino acids of this antibody via Paratome, Meta-PPISP, and the WESA web server. Subsequently, these amino acids were mutated to improve the binding affinity of the Ab variants to antigen (Ag). In this regard, the ranibizumab anti-VEGF-A was mutated. The structural docking prediction of the ranibizumab-VEGF-A complex was used for the design and validation of ranibizumab with a higher affinity for binding to VEGF-A. Finally, we measured the binding affinity of Ab variants to Ag by computational docking. Results: Bioinformatic analyzes such as molecular docking and dynamics showed that several mutant variants successfully improved the properties of Ab binding compared to the wild-type Ab. Conclusion: Consistent with the use of anti-VEGF monoclonal antibodies in the treatment of diabetic retinopathy, the mutant variants of ranibizumab may be potential candidates for stronger affinity binding to VEGF, which may affect the specificity and sensitivity of the antibody.

Discussion : L'avantage du dispositif est de proposer un dépistage, des années avant la survenue de la maladie, pour des sujets à risque comme les antécédents familiaux, les sujets à peau claire ou iris clair, les cheveux blond mais surtout plus particulièrement pour des personnes ne présentant pas ces facteurs de risque reconnus. Le dispositif, d'un usage simple, permet aussi de sensibiliser au dépistage précoce des personnes à risque. Conclusion : Cette technologie assure une reproductibilité des mesures qui permet un dépistage des personnes ayant un risque de développer une DMLA par manque de caroténoïdes dans leur rétine. L'étude de la réflectivité rétinienne par une technique rapide est efficace et fiable dans la prévention de la DMLA en permettant de proposer une supplémentation orale précoce en lutéine, zéaxanthine et méso zéaxanthine. 258 MA-15.40 Étude FRANCE DMLA 2.

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 Ͻ 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.

Purpose: To report the ocular and systemic adverse events in eyes receiving ≥10 intravitreal ziv-aflibercept (IVZ) injections. Methods: Medical records of patients who received ≥10 IVZ for various chorioretinal conditions with minimum follow up period of 12 months were retrospectively analysed. These eyes received standard dose of IVZ (1.25 mg/ 0.05 ml) on pro-re-nata (PRN) or treat and extend (T&E) protocol. The primary study outcome was ocular and systemic adverse events related to IVZ injections whereas secondary outcomes were change in best corrected visual acuity (BCVA) and central macular thickness (CMT) on optical coherence tomography (OCT) at last visit compared to baseline. Comparison of BCVA and CMT at baseline and final visit was done using paired t-test. Results: A total of 94 eyes which received a mean ± standard deviation (mean±SD = 14.4 ± 4.6) IVZ injections were studied. A total of 41 eyes were treatment naïve whereas 53 eyes received intravitreal injections in the past with last injection at least 3 months prior. Mean (±SD) follow up period was 26.7 ± 8.7 months. Ocular adverse events were limited with a case each of acute iridocyclitis, endophthalmitis, cataract progression and early epiretinal membrane formation. No systemic events were recorded within a month of IVZ injection. There was a significant improvement in BCVA (p = 0.001) and change in CMT (p = 0.001) at last visit. Conclusion: Ocular use of ziv-aflibercept is safe with limited ocular and systemic side effects. Multiple injections of IVZ can be used in various chorioretinal diseases over the long term.

Although we have been able to demonstrate that Epstein-Barr virus was present in retinal cells in an AIDS patient with cytomegalovirus retinitis, it is still unproven if Epstein-Barr virus was causing the retinitis or if it may have just been present in the tissue. Further investigations, especially in unusual cases of necrotizing retinitis, are needed to establish the role of Epstein-Barr virus coinfection in the clinical course, medical treatment, and the prognosis of cytomegalovirus-associated intraocular inflammation.

In Western Countries, the occurrence of choroidal neovascularization (CNV) secondary to different forms of macular degeneration represents a common cause of blindness. Particularly, age-related macular degeneration (AMD) and pathologic myopia (PM) are the most frequent diseases related to CNV development. At present, the combined employment of drugs acting against vascular endothelial growth factor (anti-VEGF) and photodynamic therapy with verteporfin (PDT-V) is a promising therapeutic strategy for neovascular macular degenerations. However, this approach inevitably leads to an increase in health-resource utilization. In several clusters of patients treated for CNV, correlations among common gene polymorphisms implicated in coagulation-or complement-cascade and different levels of, respectively, post-PDT-V or post-anti-VEGF benefit have been reported. Factor XIII-A G185T substitution (rs5985), a frequent anti-thrombophilic genetic variant of Caucasian ethnic groups, unequivocally influences a worsening of the CNV responsiveness to PDT-V in patients affected by either AMD-or PM-related CNV. These coherent pharmacogenetic findings point out the opportunities to: i. optimize the eligibility criteria of PDT-V and, ii. customize the interventional strategy against CNV, for finally minimizing the socioeconomic burden of neovascular macular degenerations.

To investigate whether there is an association between complement factor H (CFH) or LOC387715 genotypes with response to treatment with intravitreal bevacizumab for exudative age-related macular degeneration (AMD). Design: Retrospective cohort study. Participants: The study cohort consisted of 86 patients being treated for neovascular AMD with bevacizumab alone. Methods: Genotype determination for the CFH Y402H and LOC387715 A69S polymorphisms was performed by allele-specific digestion of polymerase chain reaction products. All patients were treated with 1.25 mg intravitreal bevacizumab at 6-week intervals until choroidal neovascularization was no longer active. Main Outcome Measures: CFH Y402H and LOC387715 A69S polymorphisms. Choroidal neovascular lesion characteristics were ascertained by fluorescein angiography. Snellen visual acuity (VA) was measured before and after treatment. Results: For the CFH Y402H polymorphism, patients with the CFH TT genotype had the largest choroidal neovascular lesions (P ϭ 0.02). With treatment, VA improved from 20/248 to 20/166 for the CFH TT genotype and from 20/206 to 20/170 for the TC genotype, but fell from 20/206 to 20/341 for the CFH CC genotype (P ϭ 0.016). Only 10.5% of patients with the CFH CC genotype demonstrated improved VA with treatment, compared with 53.7% of CFH TT and TC genotypes (P ϭ 0.004). For the LOC387715 A69S variant, patients with the TT genotype had the largest choroidal neovascular lesions (P ϭ 0.012). There was no significant difference in response to bevacizumab treatment according to LOC387715 genotype. Conclusions: The AMD-associated CFH Y402H and LOC387715 A69S variants were associated with differences in choroidal neovascular lesion size in this study. Patients with the CFH CC genotype fared significantly worse with intravitreal bevacizumab than did those with the CFH TC and TT genotypes, suggesting a potential pharmacogenetic relationship. Prospective studies to confirm or refute this observation should be considered.

PURPOSE. Oxidative stress has been implicated as a major contributor to age-related macular degeneration (AMD). 8-Hydroxy-2Ј-deoxyguanosine (8-OHdG) is one of the most abundant oxidative products of DNA damage and represents a noninvasive and sensitive biomarker of oxidative stress. The authors investigated the 8-OHdG levels in aqueous humor of patients with exudative AMD. METHODS. Twenty-four eyes of 24 patients with active exudative AMD and 31 eyes of 31 age-matched subjects who underwent cataract surgery were enrolled. Aqueous humor samples were collected from all subjects, and the 8-OHdG levels were determined by a commercially available enzyme-linked immunosorbent assay kit. The choroidal neovascularization (CNV) subtype was classified by fluorescein angiography. The macular lesion, including CNV membrane, exudation, and retinal hemorrhage, was measured. The correlation between 8-OHdG level and the clinical features was analyzed. RESULTS. The 8-OHdG level in the aqueous humor of AMD patients was significantly higher than it was in controls (0.581 Ϯ 0.258 ng/mL vs. 0.251 Ϯ 0.116 ng/mL; P Ͻ 0.001), after adjusting for age and lens status. There was no difference in the 8-OHdG levels between AMD patients with classic/ predominantly classic and occult/minimally classic CNV (0.591 Ϯ 0.262 vs. 0.566 Ϯ 0.266 ng/mL; P ϭ 0.639). The 8-OHdG level in aqueous humor was significantly correlated with the lesion size (ϭ 0.492; P ϭ 0.017). CONCLUSIONS. The 8-OHdG level in aqueous humor was higher in patients with exudative AMD, and the level was correlated with the area of macular lesion. This suggests that oxidative stress plays an important role in the disease course of AMD.

Purpose: Retinal pigment epithelial detachments (PEDs) are characterized by a separation between the RPE and the innermost aspect of Bruch&#39;s membrane. Many chorioretinal diseases can lead to pigment epithelial detachment of which the most common is age-related macular degeneration; but a significant number of PEDs are idiopathic in etiology. PEDs can be classified as drusenoid, serous, vascularized, or fibrovascular type. Currently, serous PED has not shown much response to treatment, so no specific treatment guidelines are established. Whereas vascularized PEDs, have several treatment options such as intravitreal anti-Vascular endothelial growth factor (VEGF) therapy, laser photocoagulation, photodynamic therapy (PDT) and intravitreal steroids. Hence, the need of the hour is to formulate a treatment strategy for serous PED. Methods: We report an original study of thirty patients who were diagnosed with serous pigment epithelial detachment on Spectral-domain optical coherence to...

protocols of the ANCHOR and MARINA trials (primary reports of safety and efficacy published previously 15-17) were approved by the institutional review board, national competent authority, or ethics committee at each participating clinical center before the start of the study. All United States sites were compliant with the Health Insurance Portability and Accountability Act of 1996. The 2 studies are registered at ClinicalTrials.gov (ANCHOR ID no., NCT0061594; MARINA ID no., NCT00056836). Before determination of their full eligibility for enrollment, all patients provided written, informed consent for their study participation.

Purpose This study is aimed to adapt a three-dimensional (3-D) in vitro angiogenesis model to the ophthalmology field using retinal endothelial cells (REC). This system is applied to assess the angiogenic capacity of aqueous humor (AH) from patients with ocular disorders, and to test the effect of VEGF inhibitor (aflibercept) on induced angiogenesis. Methods Human REC and umbilical vein endothelial cells (HUVEC) and pericytes were co-cultured in a gel matrix with 25-200 ng/ml pro-angiogenic growth factors (GF). AH from patients with cataract, glaucoma or proliferative diabetic retinopathy (PDR) was tested in the REC-pericyte co-culture. Aflibercept was then introduced to the co-culture containing PDR AH. The surface area and total tubule length were measured using Image J. Results Optimal GF concentrations at 200 ng/ml induced angiogenesis by REC as well as HUVEC, while vessel formation by both cell types was strongly reduced using 25-50 ng/ml GF. Addition of AH from the PDR patient triggered tubule formation by REC at low GF concentration. Aflibercept, however, significantly inhibited angiogenesis induced by PDR AH, but showed no significant influence on other conditions. Conclusion REC can be applied efficiently in the 3-D in vitro angiogenesis model as a diagnostic tool to assess the AH angiogenic status and to validate new anti-angiogenic therapeutic compounds prior to clinical trial.

PURPOSE. To study the prevalence, tomographic features, and clinical characteristics of focal choroidal excavation (FCE) in eyes with exudative age-related macular degeneration (AMD). METHODS. We examined 243 consecutive eyes with exudative AMD with a prototype sweptsource optical coherence tomography (OCT) system. Three-dimensional images of the macular area, covering 6 3 6 mm 2 , were reconstructed by segmentation of the outer surface of the retinal pigment epithelium. RESULTS. Three-dimensional swept-source OCT revealed 15 excavations in 12 eyes (4.9%); 10 had a single excavation and 2 had multiple excavations (2 and 3 excavations, respectively). In multiaveraged scans, unusual choroidal tissue was found beneath 5 excavations, bridging the excavation with the outer choroidal boundary. Additionally, the suprachoroidal space was observed beneath 7 excavations-the outer choroidal boundary appeared to be pulled inward by this bridging tissue. In 9 excavations, color fundus photographs showed pigmentary disturbance. Fourteen excavations (93.3%) were located within or adjacent to the choroidal neovascularization area. Compared with eyes without FCE, in eyes with FCE, the mean age was significantly higher (P ¼ 0.040) and mean visual acuity was significantly better (P ¼ 0.014). In addition, polypoidal lesions were observed in 8 of 12 eyes with FCE, but they appeared to have a limited effect on either the rate of FCE (P ¼ 0.44) or the clinical characteristics of the eyes. CONCLUSIONS. While FCE may be partially related to the choroidal neovascularization associated with exudative AMD, other factors may also influence this association.

Purpose: To compare functional and anatomic outcome of intravitreal ranibizumab (IVR) and intravitreal aflibercept (IVA) treatments in neovascular age-related macular degeneration by using the treat and extend (TE) protocol.Methods: In this retrospective chart study, treatment naïve 74 eyes of 74 age-related macular degeneration patients treated with IVR and IVA (38 eyes in IVR and 36 eyes in IVA group) with TE protocol were included. Following three consecutive monthly intravitreal injections, TE protocol was applied to each group. Patients were followed up for at least 36 months. Mean change in best-corrected visual acuity (BCVA), central macula thickness (CMT) and injection numbers over 3 years were compared.Results: Among 36 months period, the mean number of injections was 17 ± 4 for both groups (p &gt; 0.05). In terms of CMT, there was no statistically significant difference between groups at 36 months compared to baseline. A decrease of 72.55 ± 39.37 μm in CMT was detected in ...

Despite numerous studies describing predominantly its demography and clinical course, many aspects of central serous chorioretinopathy (CSCR) remain unclear. Perhaps the major impediment to finding an effective therapy is the difficulty of performing studies with large enough cohorts, which has meant that clinicians have focused more on therapy than on a deeper understanding of the pathogenesis of the disease. Hypotheses on the pathogenesis of CSCR have ranged from a basic alteration in the choroid to an involvement of the retinal pigment epithelium (RPE). Starting from evidence that affected subjects often present a personality prone to stress with altered pituitary-hypothalamic axis response (HPA) and that they have higher levels of serum and urinary cortisol and catecholamines than healthy subjects, we hypothesize a cascade of events that may lead to CSCR through hypercoagulability and augmented platelet aggregation. In particular we investigated the role of tissue plasminogen activator, increasing plasminogen activator inhibitor 1 (PAI-1), and plasmin-α2-plasmin inhibitor complexes. We reviewed the different therapeutic approaches, including adrenergic antagonists, carbonic anhydrase inhibitors, mifepristone, ketoconazole, laser photocoagulation, intravitreal injection of bevacizumab, and photodynamic therapy with verteporfin (PDT) and our model of pathogenesis seems to be in agreement with the clinical effects obtained from these treatments. In accord with our thesis, we began to treat a group of patients affected by CSCR with low-dose aspirin (75-100 mg), because of its effectiveness in other vascular diseases and its low ocular and general toxicity with prolonged use. The formulation of a causative model of CSCR enables us to understand how the therapeutic approach cannot be based on a generalized therapy but should be individualized for each patient, and that sometimes a combined strategy of treatment is required. Moreover a complete knowledge of the disease will help to identify patients prone to the most persistent forms of CSCR, and thus help to find a treatment.

Introduction: Multiple myeloma is the second most common hematologic cancer. It is characterized by the clonal proliferation of malignant plasma cells and associated organ dysfunction. Ophthalmic manifestations include hyperviscosity retinopathy and retinal detachment. The aim of this study is to report retinal manifestation in Multiple Myeloma. Methods: A man 45 years old, complained loss of vision on both eyes especially left eye over 1 month. He also feels weakness and 3 times spontaneous nose bleeding. His visual acquity is 6/12 on the right and 2/60 left eye with Retinal Bleeding and Retinal Detachment. His Laboratory examination result increase in WBC 65.91 x 103/µL (Neutrophil, Monocyte, Basophil and Lymphocyte) decrease RBC 3 x 106/µL, HGB 6.85 g/dL, normal PLT 193.60 103/µL, Normal Bleeding and Clotting Time and increase ESR 140 mm/hour. Multiple myeloma was diagnosed by Internal Department with bone marrow biopsy and increase of Gamma Globulin. Results: The patient was tre...

Proliferative retinopathies (PR) lead to an increase in neovascularization and inflammation factors, at times culminating in pathologic rubeosis iridis (RI). In mice, uveal puncture combined with injection of hypoxia-conditioned media mimics RI associated with proliferative retinopathies. Here, we investigated the effects of the urokinase plasminogen activator receptor (uPAR) antagonist—UPARANT—on the angiogenic and inflammatory processes that are dysregulated in this model. In addition, the effects of UPARANT were compared with those of anti-vascular endothelial growth factor (VEGF) therapies. Administration of UPARANT promptly decreased iris vasculature, while anti-VEGF effects were slower and less pronounced. Immunoblot and qPCR analysis suggested that UPARANT acts predominantly by reducing the upregulated inflammatory and extracellular matrix degradation responses. UPARANT appears to be more effective in comparison to anti-VEGF in the treatment of RI associated with PR in the mu...

• AIM: To compare two different anti-vascular endothelial growth factor (anti-VEGF) treatment regimens'-a priori pro re nata (PRN) and PRN regimen following the loading phaseanatomical and functional results in neovascular agerelated macular degeneration (nAMD) patients. • METHODS: Totally 544 nAMD patients followed and treated with aflibercept (n=135) and ranibizumab (n=409) at 9 different centers between 2013 and 2015 were enrolled into this retrospective multicenter study. Patients with initial best corrected visual acuity (BCVA) interval of 1.3-0.3 (logMAR) and a minimum follow-up of 12mo were included. Patients under two different regimens-a priori pro re nata (1+PRN) or 3 consecutive intravitreal injections followed by a PRN regimen (3+PRN)-were compared in BCVA at 3 th , 6 th and 12 th months, and in central macular thickness (CMT) at 6 th and 12 th months. The total study group, intravitreal ranibizumab (IVR) and intravitreal aflibercept (IVA) groups were evaluated separately. • RESULTS: The mean CMT decreased in the 1+PRN (n=101) regimen from 407 to 358 and 340 µm and in the 3+PRN (n=443) group from 398 to 318 and finally to 310 µm at months 6 and 12, respectively. Anatomically, the CMT reduction at 6 th month (48.5 vs 76.4; P<0.05) was statistically significant in favor of 3+PRN group. BCVA changed in 1+PRN group from 0.77 to 0.78, 0.75 and 0.75; in 3+PRN group from 0.81 to 0.69, 0.72, and 0.76 at months 3, 6, and 12, respectively. Visual gain was statistically better in 3+PRN group at 3 th month (-0.01 vs 0.12; P<0.001). In IVR group, CMT reduction was in greater in 3+PRN at 6 th (44 vs 72) and 12 th month (61 vs 84), but statistically insignificant. The 3+PRN group revealed statistically better visual results at 3 th month (-0.02 vs 0.11, P<0.05). In IVA group, although statistically insignificant, CMT reduction (61 vs 89, 6 th month; 85 vs 97, 12 th month) and visual gain (0.02 vs 0.16; 0.02 vs 0.14; 0.05 vs 0.11) was found in favor of 3+PRN group at all visits. • CONCLUSION: The loading dose of anti-VEGF treatments in nAMD leads to significantly better anatomical and functional results, regardless of the agent, specially in early follow-up interval. Effect of two different treatment regimens on AMD treatment outcome

The role of b-adrenergic receptor (AR) signaling in neovascular ocular diseases has recently emerged. We have previously reported that intraperitoneal propranolol inhibits choroidal neovascularization (CNV) in vivo and b2-AR blockade reduces vascular endothelial growth factor (VEGF) expression in mouse retinal pigment epithelium and choroidal endothelial cells in culture. Here we tested the hypothesis that the b2-AR regulates CNV through modulation of VEGF and inflammatory cytokine expression. METHODS. Mice were subjected to laser burns, inducing CNV, and were treated with an intravitreal b2-AR antagonist. After 3 and 5 days, total eye interleukin-6 (IL-6) and VEGF protein levels were measured, respectively. After 14 days, CNV was measured on choroidalscleral flatmounts. The effects of bAR signaling on VEGF and IL-6 expression were investigated in various mouse retinal and human RPE cells by using specific bAR agonists and antagonists. RESULTS. b2-Adrenergic receptor signaling increased Vegf mRNA expression by approximately 3-to 4-fold in mouse retinal microglia and pericytes in culture. b2-Adrenergic receptor signaling upregulated IL-6 mRNA expression between 10-and 60-fold in mouse retinal microglia, pericytes, RPE, and choroidal endothelial cells in culture. Intravitreal injection of b2-AR antagonist ICI 118,551 reduced CNV by 35% and decreased IL-6 protein levels by approximately 50%. In primary human RPE cells, b2-AR activation also stimulated VEGF and IL-6 mRNA expression by 2-and 10-fold, respectively. CONCLUSIONS. Anti-VEGF therapy for CNV is highly effective; however, some patients are resistant to therapy while others undergo repeated, frequent treatments. b2-Adrenergic receptor signaling is a potential therapeutic target because of its angiogenic and inflammatory properties.

This study was designed to assess the safety, tolerability, and efficacy of intravenous infusion of CA4P in patients with neovascular age-related macular degeneration (AMD). Prospective, interventional, dose-escalation clinical trial. Eight patients with neovascular AMD refractory to at least 2 sessions of photodynamic therapy received CA4P at a dose of 27 or 36 mg/m2 as weekly intravenous infusion for 4 consecutive weeks. Safety was monitored by vital signs, ocular and physical examinations, electrocardiogram, routine laboratory tests, and collection of adverse events. Efficacy was assessed using retinal fluorescein angiography, optical coherence tomography, and best corrected visual acuity (BCVA). The most common adverse events were elevated blood pressure (46.7%), QTc prolongation (23.3%), elevated temperature (13.3%), and headache (10%), followed by nausea and eye injection (6.7%). There were no adverse events that were considered severe in intensity and none resulted in discont...

Purpose: The purpose of this study is to report the first case, to our knowledge, of intracoital subfoveal hemorrhage occurring 1 hour after tadalafil premedication in a patient with previously undiagnosed retinal angiomatous proliferation and erectile dysfunction. Methods: This is an interventional case report. The patient underwent Snellen vision acuity measurement, anterior and posterior segment biomicroscopy, and indirect ophthalmoscopy. Optical coherence tomography, fluorescein angiography, and indocyanine green angiography were also performed as needed. Recombinant tissue plasminogen activator 100 mg/0.1 mL and 0.3 mL pure SF6 gas were injected in the vitreous on presentation. Four days later, the patient received 1.25 mg/0.1 mL of intravitreal bevacizumab. Results: One day after recombinant tissue plasminogen activator and gas injection, visual acuity rose to 20/60-2. A week later, visual acuity was unchanged, and the subretinal hemorrhage displaced from the foveola. Optical coherence tomography showed a marked regression of submacular thickening. Conclusion: Despite strict time correlation, the submacular hemorrhage cannot be unequivocally attributed to tadalafil assumption because many other risk factors are to be considered: the Valsalva maneuver above all. Nonetheless, a suspicion should be raised, at least as a cofactor, given the drug mechanism of action and the report of vascular abnormalities bleeding in the literature, including cerebral arterovenous malformation and epistaxis. Caution should be exercised in the prescription of phosphodiesterase type 5 inhibitors to patients with known vascular abnormalities including retinal and choroidal abnormalities: retinal angiomatous proliferation, classic and occult neovascularization of any origin, and also, possibly, hemangioma.