The Anti-Inflammatory Effect of Hydrogen Gas Inhalation and Its Influence on Laser-Induced Choroidal Neovascularization in a Mouse Model of Neovascular Age-Related Macular Degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. Choroidal neovascularization (CNV) is the major pathologic feature of neovascular AMD. Oxidative damages and the ensuing chronic inflammation are representative of trigger events. Hydrogen gas (H2) has been demonstrated as an antioxidant and plays a role in the regulation of oxidative stress and inflammation. This experiment aimed to investigate the influence of H2 inhalation on a mouse model of CNV. METHODS: Laser was used to induce CNV formation. C57BL/6J mice were divided into five groups: the control group; the laser-only group; and the 2 h, 5 h, and 2.5 h/2.5 h groups that received laser and H2 inhalation (21% oxygen, 42% hydrogen, and 37% nitrogen mixture) for 2 h, 5 h, and 2.5 h twice every day, respectively. RESULTS: The severity of CNV leakage on fluorescence angiography showed a significant decrease in the H2 inhalation groups. The mRNA expression of hypoxia-inducible factor 1 alpha and its immediate downstream target vascular endothelial growth factor (VEGF) showed significant elevation after laser, and this elevation was suppressed in the H2 inhalation groups in an inhalation period length-related manner. The mRNA expression of cytokines, including tumor necrosis factor alpha and interlukin-6, also represented similar results. CONCLUSION: H2 inhalation could alleviate CNV leakage in a laser-induced mouse CNV model, and the potential mechanism might be related to the suppression of the inflammatory process and VEGF-driven CNV formation.

THE RAP STUDY, REPORT TWO: The Regional Distribution of Macular Neovascularization Type 3, a Novel Insight Into Its Etiology.

PURPOSE: To explore the regional distribution of macular neovascularization type 3 (MNV3). METHODS: Seventy-eight eyes of 78 patients were reviewed. We defined the location of each lesion after applying a modified ETDRS grid and the incidence of simultaneous MNV1 or 2. Also, we investigated the distribution of MNV3 at the outline of the foveal avascular zone and when the diameter of foveal avascular zone was less than 325 µm. RESULTS: The distribution of MNV3 was 4 lesions (5%) from the center to 500 µm, 72 (92%) from 500 µm to 1500 µm, and 2 (3%) from 1,500 µm to 3000 µm. The distribution in respect of the ETDRS fields was 7 (9%) nasal, 16 (20%) superior, 32 (40%) temporal, and 23 (31%) inferior. No additional MNV1 or 2 were found elsewhere. Most lesions tended to distribute along straight bands radiating from the perifoveal area, mainly in the temporal half (72%). None of the cases had MNV3 at the boundary of the foveal avascular zone. Only five cases had foveal avascular zone diameter of less than 325 µm, the closest lesion was 425 µm away from the center. CONCLUSION: MNV3 lesions are most likely neither symmetrical nor uniformly distributed. They have a higher affinity to distribute radially in the temporal perifoveal area.

Targeted Imaging of VCAM-1 mRNA in a Mouse Model of Laser-Induced Choroidal Neovascularization Using Antisense Hairpin-DNA-Functionalized Gold-Nanoparticles.

Mouse laser-induced choroidal neovascularization (mouse LCNV) recapitulates the "wet" form of human age-related macular degeneration (AMD). Vascular cell adhesion molecule-1 (VCAM-1) is a known inflammatory biomarker, and it increases in the choroidal neovascular tissues characteristic of this experimental model. We have designed and constructed gold nanoparticles (AuNPs) functionalized with hairpin-DNA that incorporates an antisense sequence complementary to VCAM-1 mRNA (AS-VCAM-1 hAuNPs) and tested them as optical imaging probes. The 3' end of the hairpin is coupled to a near-infrared fluorophore that is quenched by the AuNP surface via Förster resonance energy transfer (FRET). Hybridization of the antisense sequence to VCAM-1 mRNA displaces the fluorophore away from the AuNP surface, inducing fluorescent activity. In vitro testing showed that hAuNPs hybridize to an exogenous complementary oligonucleotide within a pH range of 4.5-7.4, and that they are stable at reduced pH. LCNV mice received tail-vein injections of AS-VCAM-1 hAuNPs. Hyperspectral imaging revealed the delivery of AS-VCAM-1 hAuNPs to excised choroidal tissues. Fluorescent images of CNV lesions were obtained, presumably in response to the hybridization of AS-hAuNPs to LCNV-induced VCAM-1 mRNA. This is the first demonstration of systemic delivery of hAuNPs to ocular tissues to facilitate mRNA imaging of any target.

Development of Age-Related Macular Degeneration (AMD) in the Fellow Eye of Patients with AMD Treated by Treat-and-Extend Intravitreal Therapy with Aflibercept.

PURPOSE: To evaluate the development of neovascular age-related macular degeneration (nAMD) in the fellow eye in patients with unilateral nAMD treated by a treat-and-extend (TAE) regimen with intravitreal aflibercept injections. METHODS: We retrospectively studied 104 patients with treatment-naïve unilateral nAMD. We assessed best-corrected visual acuity (BCVA) and exudative changes in the treated eyes and development of nAMD in the fellow eye for 2 years. RESULTS: The subjects included 46 patients with typical AMD (tAMD), 44 with polypoidal choroidal vasculopathy (PCV), and 14 with retinal angiomatous proliferation (RAP). BCVA was significantly improved after the loading phase in all subtypes. Forty-six patients (44.2%) had no recurrence within 2 years after the loading phase, including 12 (26.1%) with tAMD, 23 (52.2%) with PCV, and 11 (78.6%) with RAP (p < 0.01). Eleven patients (10.6%) developed nAMD in the fellow eye within 2 years, including 4 (8.7%) with tAMD, 0 (0%) with PCV, and 7 (50.0%) with RAP (p < 0.001). CONCLUSIONS: Patients with RAP had significantly more frequent development of nAMD in the fellow eye compared to other subtypes, while they showed significantly less recurrence during the TAE regimen with intravitreal aflibercept injections. Development of nAMD in the fellow eye should be monitored in RAP when the injection interval is extended.

Vitreomacular Adhesion and the Risk of Neovascular Age-Related Macular Degeneration.

PURPOSE: To assess the prevalence of vitreomacular adhesion (VMA) in consecutive naïve eyes diagnosed with exudative age-related macular degeneration (AMD) in comparison with eyes with nonexudative AMD and age-matched controls, and to evaluate prospectively the incidence of vitreomacular interface changes over time and their influence on choroidal neovascularization (CNV) development. DESIGN: Retrospective cross-sectional analysis and longitudinal cohort study conducted at Sacrocuore Hospital, Negrar, Verona, Italy. PARTICIPANTS: A total of 1067 eyes examined at Sacrocuore Hospital between August 2008 and June 2015 met the inclusion criteria and were evaluated in this study. METHODS: Eyes were classified into 3 groups: 403 eyes of 364 patients (mean [standard deviation; SD] age 77.8 [8.0] years) affected by exudative AMD; 350 eyes of 298 subjects (mean [SD] age 78.1 [8.2] years) with nonexudative AMD; and 314 eyes of 214 subjects (mean [SD] age 74.2 [8.2] years) with no signs of AMD enrolled as the control group. The vitreomacular interface status was evaluated by spectral-domain optical coherence tomography (OCT) and was graded according to the OCT-based International Classification System developed by the International Vitreomacular Traction Study Group by 2 independent masked observers. RESULTS: VMA was present in 101 (25.1%) eyes with exudative AMD, 84 (24.0%) eyes with nonexudative AMD, and 84 (26.8%) eyes with no signs of AMD (no statistical difference was found; P = 0.3384). Spontaneous release of VMA (RVMA) was found in 15 (15.3%) eyes with exudative AMD, 21 (28.0%) eyes with nonexudative AMD, and 10 (24.4%) eyes with no signs of AMD over a mean follow-up of 25.5, 25.9, and 24.1 months, respectively. The incidence of RVMA in exudative AMD eyes was significantly lower compared with nonexudative (P = 0.0207) and lower, but not statistically significant, with respect to eyes with no signs of AMD (P = 0.1013). In eyes with nonexudative AMD, de novo development of CNV occurred in 91 eyes (30.6%). There was no significant difference regarding the rate of CNV development in the presence or absence of VMA (P = 0.0966). CONCLUSIONS: The present study found no significant difference in the prevalence of VMA in eyes affected by AMD compared with age-matched controls and no difference in the rate of de novo CNV development in eyes with or without VMA. Conversely, a lower incidence of RVMA over time was found in eyes affected by exudative AMD. The results of this study suggest that VMA might be a consequence rather than a causative factor in the development of CNV.

Influence of Vitreomacular Adhesion on Anti-Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration.

PURPOSE: To investigate the effect of vitreomacular adhesion (VMA) on the outcome of antiangiogenic treatment for neovascular age-related macular degeneration (AMD). METHODS: Ninety-nine eyes of 83 patients were used in our cohort study. We prospectively evaluated best corrected visual acuity (BCVA) and central retinal thickness (CRT) in patients with neovascular AMD at baseline and 1, 2, 3, 6, and 12 months after treatment with anti-vascular endothelial growth factor (anti-VEGF) agents. All patients were stratified by spectral domain optical coherence tomography into 2 groups (i.e., VMA[+] and VMA[-]) according to the presence or absence of VMA, and the response to treatment was evaluated. RESULTS: Fifty-four eyes (54.5%) were included in the VMA(-) group and 45 eyes (45.5%) comprised the VMA(+) group. In paired comparisons of mean BCVA between baseline and each follow-up visit (1, 2, 3, 6, and 12 months), the VMA(-) group showed statistically significant improvement at 1, 2, and 3 months compared to baseline, and BCVA significantly improved only at 3 months in the VMA(+) group. For both groups, paired comparisons of CRT showed a statistically significant decrease when data obtained at 1, 2, 3, 6, and 12 months were compared to baseline values (p < 0.05). CONCLUSIONS: Posterior VMA is associated with a worse short-term outcome in patients with neovascular AMD treated with anti-VEGF agents.

Gene therapy with recombinant adeno-associated vectors for neovascular age-related macular degeneration: 1 year follow-up of a phase 1 randomised clinical trial.

BACKGROUND: Neovascular, or wet, age-related macular degeneration causes central vision loss and represents a major health problem in elderly people, and is currently treated with frequent intraocular injections of anti-VEGF protein. Gene therapy might enable long-term anti-VEGF therapy from a single treatment. We tested the safety of rAAV.sFLT-1 in treatment of wet age-related macular degeneration with a single subretinal injection. METHODS: In this single-centre, phase 1, randomised controlled trial, we enrolled patients with wet age-related macular degeneration at the Lions Eye Institute and the Sir Charles Gairdner Hospital (Nedlands, WA, Australia). Eligible patients had to be aged 65 years or older, have age-related macular degeneration secondary to active subfoveal choroidal neovascularisation, with best corrected visual acuity (BCVA) of 3/60-6/24 and 6/60 or better in the other eye. Patients were randomly assigned (3:1) to receive either 1 × 10(10) vector genomes (vg; low-dose rAAV.sFLT-1 group) or 1 × 10(11) vg (high-dose rAAV.sFLT-1 group), or no gene-therapy treatment (control group). Randomisation was done by sequential group assignment. All patients and investigators were unmasked. Staff doing the assessments were masked to the study group at study visits. All patients received ranibizumab at baseline and week 4, and rescue treatment during follow-up based on prespecified criteria including BCVA measured on the Early Treatment Diabetic Retinopathy Study (EDTRS) scale, optical coherence tomography, and fluorescein angiography. The primary endpoint was ocular and systemic safety. This trial is registered with ClinicalTrials.gov, number NCT01494805. FINDINGS: From Dec 16, 2011, to April 5, 2012, we enrolled nine patients of whom eight were randomly assigned to receive either intervention (three patients in the low-dose rAAV.sFLT-1 group and three patients in the high-dose rAAV.sFLT-1 group) or no treatment (two patients in the control group). Subretinal injection of rAAV.sFLT-1 was highly reproducible. No drug-related adverse events were noted; procedure-related adverse events (subconjunctival or subretinal haemorrhage and mild cell debris in the anterior vitreous) were generally mild and self-resolving. There was no evidence of chorioretinal atrophy. Clinical laboratory assessments generally remained unchanged from baseline. Four (67%) of six patients in the treatment group required zero rescue injections, and the other two (33%) required only one rescue injection each. INTERPRETATION: rAAV.sFLT-1 was safe and well tolerated. These results support ocular gene therapy as a potential long-term treatment option for wet age-related macular degeneration. FUNDING: National Health and Medical Research Council of Australia, Richard Pearce Bequest, Lions Save Sight Foundation, Brian King Fellowship, and Avalanche Biotechnologies, Inc.

Arteriosclerotic Changes after Intravitreal Injections of Anti-Vascular Endothelial Growth Factor Drugs in Patients with Exudative Age-Related Macular Degeneration.

PURPOSE: The aim of this study was to determine whether multiple intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs for age-related macular degeneration (AMD) exacerbate systemic arteriosclerosis, using the cardio-ankle vascular index (CAVI) and intima-media thickness (IMT). METHODS: We analyzed the data of 45 AMD patients who received intravitreal injections of anti-VEGF drugs (ranibizumab and/or aflibercept) and underwent systemic evaluations at baseline and after treatment. Reevaluation was conducted at ≥12 months from the initial treatment. RESULTS: The total number of intravitreal injections of overall anti-VEGF drugs was significantly correlated with x0394;serum cystatin C. The cumulative number of aflibercept injections was identified as an independent protective factor for x0394;CAVI. An increase in the cumulative number of intravitreal injections of overall anti-VEGF drugs was identified as a protective factor for x0394;mean IMT. CONCLUSION: Repeated intravitreal injections of an anti-VEGF drug for AMD may lead to morphological and functional changes in large arteries.

The Onion Sign in Neovascular Age-Related Macular Degeneration Represents Cholesterol Crystals.

PURPOSE: To investigate the frequency, natural evolution, and histologic correlates of layered, hyperreflective, subretinal pigment epithelium (sub-RPE) lines, known as the onion sign, in neovascular age-related macular degeneration (AMD). DESIGN: Retrospective observational cohort study and experimental laboratory study. PARTICIPANTS: Two hundred thirty eyes of 150 consecutive patients with neovascular AMD and 40 human donor eyes with histopathologic diagnosis of neovascular AMD. METHODS: Spectral-domain optical coherence tomography (SD OCT), near-infrared reflectance (NIR), color fundus images, and medical charts were reviewed. Donor eyes underwent multimodal ex vivo imaging, including SD OCT, before processing for high-resolution histologic analysis. MAIN OUTCOME MEASURES: Presence of layered, hyperreflective sub-RPE lines, qualitative analysis of their change in appearance over time with SD OCT, histologic correlates of these lines, and associated findings within surrounding tissues. RESULTS: Sixteen of 230 eyes of patients (7.0%) and 2 of 40 donor eyes (5.0%) with neovascular AMD had layered, hyperreflective sub-RPE lines on SD OCT imaging. These appeared as refractile, yellow-gray exudates on color imaging and as hyperreflective lesions on NIR. In all 16 patient eyes, the onion sign persisted in follow-up for up to 5 years, with fluctuations in the abundance of lines and association with intraretinal hyperreflective foci. Patients with the onion sign disproportionately were taking cholesterol-lowering medications (P=0.025). Histologic analysis of 2 donor eyes revealed that the hyperreflective lines correlated with clefts created by extraction of cholesterol crystals during tissue processing. The fluid surrounding the crystals contained lipid, yet was distinct from oily drusen. Intraretinal hyperreflective foci correlated with intraretinal RPE and lipid-filled cells of probable monocytic origin. CONCLUSIONS: Persistent and dynamic, the onion sign represents sub-RPE cholesterol crystal precipitation in an aqueous environment. The frequency of the onion sign in neovascular AMD in a referral practice and a pathology archive is 5% to 7%. Associations include use of cholesterol-lowering medication and intraretinal hyperreflective foci attributable to RPE cells and lipid-filled cells of monocyte origin.

[Progression of treatment and researches in dry age related macular degeneration].

Age related macular degeneration (AMD) is the leading cause of blindness and visual disability among old patients in Europe and North America. AMD has been divided into two broad clinical categories depending on whether there is a presence of abnormal neovascularization: neovascular (exudative or wet) AMD and dry (or geographic atrophic) AMD. VEGF has been understood as a pathogenesis of wet AMD which allows us to get breakthroughs in treatment. While the progression of dry AMD treatment is very slow because the lack of pathogenesis, no acute loss of vision, and without appropriate standards for treatment. This review tries to introduce about the recent researches and progressions for dry AMD treatment.

[The role of laser photocoagulation in the anti-vascular endothelial growth factor therapy era].

Anti-vascular endothelial growth factor (VEGF) therapy has recently become the first-line treatment for wet age related macular degeneration, macular edema secondary to diabetic retinopathy and retinal vein occlusion, retinopathy of prematurity and neovascular glaucoma. It is worth thinking about whether laser photocoagulation still has its therapeutic value in these diseases. The purpose of this article is to discuss the role of laser photocoagulation in the anti-VEGF therapy era. And the article also discussed the combined treatment strategy in order to avoid clinical errors and to provide a new insight for prevention and treatment of ocular neovascular disease in the future.

Extramacular Drusen and Progression of Age-Related Macular Degeneration: Age Related Eye Disease Study 2 Report 30.

PURPOSE: To identify the prevalence of extramacular drusen and their role in the progression of age-related macular degeneration (AMD). DESIGN: Retrospective analysis of a prospective cohort study. PARTICIPANTS: The study was conducted in 4168 eyes (2998 participants) with intermediate AMD in one or both eyes enrolled in the Age-Related Eye Disease Study 2 (AREDS2), a 5-year multicenter study of nutritional supplements. METHODS: Baseline 3-field 30-degree color photographs were evaluated for drusen characteristics outside the macular grid, including size, area, and location. The characteristics of extramacular drusen were compared with those of drusen within the macula. MAIN OUTCOME MEASURES: Progression rates to late AMD. RESULTS: Although extramacular drusen were observed in 3624 (86.9%) eyes, they represented a small area (< 0.5 mm2) in 50.3% of eyes, with only 17.5% exhibiting an area of > 1 disc area. Eyes with extramacular drusen exhibited larger macular drusen size and area than eyes without extramacular drusen (P < 0.001). Extramacular drusen were not associated with progression to late AMD. The hazard ratio adjusted for baseline age, sex, smoking, AMD severity level, and reticular pseudodrusen for 4043 eyes at risk of developing late AMD over 5 years was 1.17 (95% confidence interval [CI], 0.88-1.54; P = 0.27) for geographic atrophy and 0.96 (95% CI, 0.76-1.2; P = 0.7) for neovascular AMD. CONCLUSIONS: Extramacular drusen are commonly observed in eyes with AMD and are more frequent with an increasing drusen burden within the macula. In eyes with intermediate AMD, extramacular drusen do not confer additional risk to previously identified risk factors in progression to late AMD.

Risk of age-related macular degeneration 3 years after cataract surgery: paired eye comparisons.

OBJECTIVE: To clarify possible associations between cataract surgery and progression of age-related macular degeneration (AMD). DESIGN: Clinic-based cohort. PARTICIPANTS: We followed cataract surgical patients aged 65+ years in the Australian Cataract Surgery and Age-related Macular Degeneration (CSAMD) study. Patients who remained unilaterally phakic for at least 24 months after recruitment were included. METHODS: We performed annual examinations with retinal photography. We assessed AMD using side-by-side grading of images from all visits. Paired comparisons between operated and nonoperated fellow eyes (defined as nonoperated or operated <12 months previously) were made using generalized estimating equation models. MAIN OUTCOME MEASURES: Incident early AMD was defined as the new appearance of soft indistinct/reticular drusen or coexisting retinal pigmentary abnormality and soft distinct drusen in eyes at risk of early AMD. Incident late AMD was defined as the new appearance of neovascular AMD or geographic atrophy (GA) in eyes at risk of late AMD. RESULTS: Among 2029 recruited, eligible participants, 1851 had cataract surgery performed at Westmead Hospital, Sydney, and 1244 (70.7%) had 36-month postoperative visits. Of these participants, 1178 had gradable photographs at baseline and at least 1 follow-up visit. Of 308 unilaterally operated participants at risk of late AMD, this developed in 4 (1.3%) operated and 7 (2.3%) nonoperated fellow eyes (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.23-2.36) after adjusting for the presence of early AMD at baseline. Of 217 unilaterally operated participants at risk of early AMD, this developed in 23 (10.6%) operated and 21 (9.7%) nonoperated fellow eyes (OR, 1.07; 95% CI, 0.74-1.65). Incident retinal pigment abnormalities were more frequent in operated than nonoperated fellow eyes (15.3% vs. 9.9%; OR, 1.64; 95% CI, 1.07-2.52). There was no difference in the 3-year incidence of large soft indistinct or reticular drusen between the 2 eyes (8.8% vs. 7.9%; OR, 1.12; 95% CI, 0.79-1.60). CONCLUSIONS: Prospective follow-up data and paired eye comparisons of this older surgical cohort showed no increased risk of developing late AMD, early AMD, or soft/reticular drusen over 3 years. There was a 60% increased detection of retinal pigmentary changes in surgical eyes.

[Experience of Lucentis use in patients with wet age-related macular degeneration].

This article provides information about development and introduction of regional standard of specialized medical care for patients with neovascular age-related macular degeneration in medical practice in Tumen region. It discovered new opportunities for improvement of ophthalmologic care in the region.

Optimization of laser-induced choroidal neovascularization in African green monkeys.

We developed and validated a new nonhuman primate model of laser-induced choroidal neovascularization (CNV) that addresses study design limitations prevalent in laser-induced CNV-based efficacy studies. Laser-induced Bruch's membrane disruption triggers CNV and has been widely utilized in animals to model neovascular ("wet") age-related macular degeneration (AMD). Despite widespread use of the approach, detailed assessment of experimental parameters and their influence on pathophysiological endpoints critical for disease modeling has been extremely limited and largely based on anecdotal observations. We evaluated laser power parameters and endpoint measures to optimize methods for CNV formation and quantification to facilitate drug efficacy screening in African green monkeys. Six laser spots of 350, 550, 750, 950 or 1500 mW laser power were positioned bilaterally 1.5 disc diameters from the fovea, within the macula. Fluorescein angiograms were collected 3-5 weeks later and scored by trained masked investigators using graded (I-IV) and densitometric methods. Histopathology assessments were also performed, including determination of CNV area. Test system sensitivity to angiogenesis inhibition was subsequently assessed by evaluating the effect of intravitreal bevacizumab (Avastin) pretreatment (one day prior to laser photocoagulation) on incidence of CNV. Grade III and grade IV lesions were considered clinically relevant, demonstrating early hyperfluorescence and late leakage within or beyond the lesion borders. By 4 weeks post-laser all treatment groups demonstrated evidence of grade III lesions with greatest incidence observed in lesions induced by 750 and 950 mW laser power (72.9% and 69.4% respectively). Grade IV lesions were confined to eyes receiving 550 mW laser power or higher, with highest incidence of grade IV lesions observed in eyes receiving 950 (19.4%) and 1500 mW (31%) laser spots, incidence peaking 4 weeks post-laser photocoagulation. Densitometric analyses of angiograms corroborated visual scoring. Bevacizumab completely abolished grade IV lesion development and significantly lowered lesion fluorescein signal intensity (P < 0.0001) and CNV area (P = 0.038) compared to vehicle-treated controls. Our studies demonstrate that laser power of 950-1500 mW and angiography analysis 4 weeks post-laser are optimal parameters to evaluate treatment effects on CNV induction following laser photocoagulation. Bevacizumab significantly attenuated CNV development, as determined by fluorescein angiography and histopathology assessments in this model, supporting the application of African green monkeys in preclinical modeling of CNV. Laser parameters and time points for therapeutic dosing and angiography endpoints are critical factors to the laser-induced CNV model and must be validated for robust assessment of efficacy. The newly optimized nonhuman primate model described will facilitate preclinical efficacy assessments of novel therapeutics for CNV.

Age-related macular degeneration and risk factors for the development of choroidal neovascularisation in the fellow eye: a 3-year follow-up study.

INTRODUCTION: The presence of large-sized drusen (≥125 µm), soft indistinct drusen, pigmentary changes, a large area of drusen and a choroidal neovascular membrane in one eye have been found to be predictive risk factors of late exudative age-related macular degeneration (AMD). Multimodal imaging potentially increases the possibility of indentifying further potential risk factors of developing wet AMD. PURPOSE: To identify morphological and/or functional baseline risk factors for the development of choroidal neovascularization (CNV) in a multimodal set of images from fellow eyes of patients with exudative AMD. METHODS: Single-center, prospective, observational, longitudinal 2-year plus 1-year extension study of 62 patients with neovascular AMD in one eye (the nonstudy eye) and early age-related maculopathy (ARM) in the fellow eye (study eye). Best-corrected ETDRS visual acuity, fluorescein angiography (FA) and indocyanine green angiography (ICG), fundus photography, retinal leakage analysis, fundus autofluorescence imaging and optical coherence tomography (OCT Stratus 4.0.2, Carl Zeiss Meditech Inc.) were performed at baseline and every 6 months in order to identify both conversion to CNV as well as possible predictive features present before conversion. A semiautomated computer-assisted grading system was used for classifying fundus color images. Only eyes with 3 years of follow-up were considered for statistical analysis. RESULTS: Fifty-two patients completed the 3-year study follow-up: 26 men and 26 women aged from 56 to 92 years (mean ± SD: 76 ± 6 years). CNV confirmed with FA developed in 46% of the 52 study eyes during the 3-year follow-up (24 converted eyes: 7 in the first year, 11 in the second and 6 in the third). A significantly higher risk for conversion to wet AMD was found only for leakage on a retinal leakage analyzer (odds ratio, OR = 5.0; 95% confidence interval, CI = 1.5-16.4; p = 0.006) detected at least in one visit before the onset of exudative lesions, for baseline ICG hot spots (OR = 7.2; 95% CI = 2.0-25.7; p = 0.002), baseline late ICG hot spots (OR = 4.7; 95% CI = 1.4-15.4; p = 0.009) and baseline early ICG hypofluorescent spots (OR = 3.7; 95% CI = 1.2-12.1; p = 0.025). The total area of drusen, the area of drusen in subfield 1, inner circle or outer circle, the total number of drusen and the number of drusen ≥125 µm, fundus autofluorescence patterns, OCT findings and the severity of ARM at baseline did not show any correlation with an increased risk of conversion to wet AMD. CONCLUSION: At 3 years, progression from early to late exudative AMD was superior to the expected rate (44%). ICG early and late hyperfluorescent spots or areas, ICG early hypofluorescent spots or areas and early leakage detected with the retinal leakage analyzer, but not pigmentary changes, large drusen, number and area of drusen at any location or a greater severity of ARM at baseline, showed to be a predictive parameter of conversion to wet AMD.

[Anti VEGF therapy in different forms of wet ARMD]. / Tratamentul anti-VEGF în diferite forme anatomice ale DMLV exudative.

The article presents anti-VEGF therapy in different forms of wet ARMD.

TPC2 promotes choroidal angiogenesis and inflammation in a mouse model of neovascular age-related macular degeneration.

Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly and can be classified either as dry or as neovascular (or wet). Neovascular AMD is characterized by a strong immune response and the inadequate release of cytokines triggering angiogenesis and induction of photoreceptor death. The pathomechanisms of AMD are only partly understood. Here, we identify the endolysosomal two-pore cation channel TPC2 as a key factor of neovascularization and immune activation in the laser-induced choroidal neovascularization (CNV) mouse model of AMD. Block of TPC2 reduced retinal VEGFA and IL-1ß levels and diminished neovascularization and immune activation. Mechanistically, TPC2 mediates cationic currents in endolysosomal organelles of immune cells and lack of TPC2 leads to reduced IL-1ß levels in areas of choroidal neovascularization due to endolysosomal trapping. Taken together, our study identifies TPC2 as a promising novel therapeutic target for the treatment of AMD.

Progression of Geographic Atrophy with Subsequent Exudative Neovascular Disease in Age-Related Macular Degeneration: AREDS2 Report 24.

PURPOSE: To examine whether the rate of geographic atrophy (GA) enlargement is influenced by subsequent exudative neovascular age-related macular degeneration (nAMD) and hence, to explore indirectly whether nonexudative nAMD may slow GA enlargement. DESIGN: Post hoc analysis of a controlled clinical trial cohort. PARTICIPANTS: Age-Related Eye Disease Study 2 participants 50 to 85 years of age. METHODS: Baseline and annual stereoscopic color fundus photographs were evaluated for (1) GA presence and area and (2) exudative nAMD presence. Two cohorts were constructed: eyes with GA at study baseline (prevalent cohort) and eyes in which GA developed during follow-up (incident cohort). Mixed-model regression of the square root of GA area was performed according to the presence or absence of subsequent exudative nAMD. MAIN OUTCOME MEASURES: Change over time in square root of GA area. RESULTS: Of the 757 eyes in the incident GA cohort, over a mean follow-up of 2.3 years (standard deviation [SD], 1.2 years), 73 eyes (9.6%) demonstrated subsequent exudative nAMD. Geographic atrophy enlargement in these eyes was significantly slower (0.20 mm/year; 95% confidence interval [CI], 0.12-0.28 mm/year) compared with the other 684 eyes in which subsequent exudative nAMD did not develop (0.29 mm/year; 95% CI, 0.27-0.30 mm/year; P = 0.037). Of the 456 eyes in the prevalent GA cohort, over a mean follow-up of 4.1 years (SD, 1.4 years), 63 eyes (13.8%) demonstrated subsequent exudative nAMD. Geographic atrophy enlargement in these eyes was similar (0.31 mm/year; 95% CI, 0.24-0.37 mm/year) compared with the other 393 eyes in which subsequent exudative nAMD did not develop (0.28 mm/year; 95% CI, 0.26-0.29 mm/year; P = 0.37). CONCLUSIONS: In eyes with recent GA, GA enlargement before the development of exudative nAMD seems slowed. This association was not observed in eyes with more long-standing GA, which have larger lesion sizes. Hence, perilesional nonexudative choroidal neovascular tissue (presumably present before the development of clinically apparent exudation) may slow enlargement of smaller GA lesions through improved perfusion. This hypothesis warrants further evaluation in prospective studies.

Care of patients undergoing intra-vitreal therapy.

This article discusses the role of the ophthalmic nurse in the care of patients with wet age-related macular degeneration who are undergoing intra-vitreal therapy. It provides an overview of the condition, its classification, clinical features, aetiology, diagnosis and treatment, and explains the implications for future nursing practice. A proactive, evidence-based and holistic approach to nursing care is emphasised throughout the article.