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.

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.

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.

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.

The association between clinically diagnosed insomnia and age-related macular degeneration: a population-based cohort study.

PURPOSE: The decreased level of melatonin, the substance involved in the control of the sleep-wake cycle, has been reported among the patients with age-related macular degeneration (AMD). However, knowledge about the relationship between sleep disturbance and AMD is still limited. This longitudinal case-control study aims to investigate the risk of incident AMD among the patients with clinically diagnosed insomnia using the Taiwan National Health Insurance Research Database. METHODS: The insomnia cohort (n = 15 465) consisted of newly diagnosed insomnia cases aged ≥55 years between 2000 and 2009. Subjects without insomnia, matched for age, gender and enrolment time, were randomly sampled as the control cohort (n = 92 790). Cox proportional hazard regressions were performed to calculate the hazard ratios (HR) of incident AMD for the two cohorts after adjusting for potential confounders. RESULTS: Of the 108 255 sampled subjects, 2094 (1.9%) were diagnosed with AMD, including 214 (0.2%) with neovascular AMD, during a mean follow-up period of 5.1 ± 2.8 years. Insomnia patients were more likely to have subsequent AMD than those without insomnia (2.5% versus 1.8%, p < 0.001). Further, the incidence of exudative AMD was also higher in the insomnia cohort than the control cohort (0.3% versus 0.2%, p = 0.002). The adjusted HR was 1.33 (95% confidence interval [CI], 1.18-1.48, p < 0.001) for AMD and 1.67 (95% CI, 1.20-2.33, p = 0.002) for exudative AMD. CONCLUSIONS: Clinically diagnosed insomnia is an independent indicator for the increased risk of subsequent AMD development.

Pseudodrusen pattern and development of late age-related macular degeneration in the fellow eye of the unilateral case.

PURPOSE: To investigate whether the development of late age-related macular degeneration (AMD) in fellow eyes with pseudodrusen is associated with the pseudodrusen pattern in patients with unilateral exudative AMD. STUDY DESIGN: Retrospective observational study. METHODS: A retrospective analysis was performed on 73 patients with unilateral exudative AMD showing pseudodrusen in their fellow eyes. Eyes were classified according to pseudodrusen pattern, which was determined based on maximum pseudodrusen ribbon length. RESULTS: During the mean follow-up period of 35.5±18.6 months, 21 (28.8%) eyes developed late AMD. Among these eyes, 15 (71%) developed exudative AMD and six (29%) developed geographic atrophy (GA). Development of late AMD in fellow eyes occurred with significantly more prevalence in patients showing a ribbon-dominant type pseudodrusen pattern in their fellow eye than dot-dominant type (P=0.0005, log-rank test). Cox-regression analysis revealed that development of late AMD in fellow eyes is associated with the presence of ribbon-dominant pseudodrusen in the fellow eyes (hazard ratio 4.15, 95% confidence interval (CI) 1.59-10.8), along with older age (hazard ratio 1.10, 95% CI 1.03-1.17), a history of smoking (hazard ratio 17.2, 95% CI 1.11-263), the presence of large soft drusen in the fellow eye. (hazard ratio 5.49, 95% CI 1.29-21.1) and retinal angiomatous proliferation (hazard ratio 5.02, 95% CI 1.90-13.2) CONCLUSIONS: Fellow eyes with ribbon-dominant pseudodrusen in patients with unilateral exudative AMD are likely to develop late AMD.

An Evaluation of the Relationship Between Clinically Unilateral Pseudoexfoliation Syndrome and Age-Related Macular Degeneration.

BACKGROUND AND OBJECTIVE: To evaluate the relationship between age-related macular degeneration (AMD) and clinically unilateral pseudoexfoliation syndrome (XFS). PATIENTS AND METHODS: Seventy-six patients (152 eyes) with bilateral AMD and clinically unilateral XFS were included. Eyes with AMD were divided into three stages (early, intermediate, and late), based on the Beckman Initiative for Macular Research Classification Committee of fundus findings. The distribution of AMD lesions was assessed in both groups, and the subfoveal choroidal thickness (SFCT) was measured using enhanced depth imaging spectral-domain optical coherence tomography (SD-OCT). RESULTS: There were significantly more early and intermediate-stage AMD cases in eyes with XFS than in non-XFS fellow eyes (P < .05). In contrast, there were significantly fewer wet AMD cases in XFS eyes than in non-XFS fellow eyes (P < .05). SFCT in all AMD stages was significantly lower in eyes with XFS (P < .05). CONCLUSION: XFS was associated with a lower prevalence of wet AMD. Further studies are required to elucidate this association. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:12-19.].

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.

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.

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.

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.

Vascular endothelial growth factor inhibitor use and treatment approach for choroidal neovascularization secondary to pathologic myopia.

INTRODUCTION: Myopic choroidal neovascularization (CNV) is the most common cause of CNV in those under 50 years of age. It is a significant cause of visual loss in those with pathologic myopia. The current standard of care involves therapy with intravitreal inhibitors of vascular endothelial growth factor (VEGF). AREAS COVERED: The epidemiology of myopia, high myopia, pathologic myopia, and myopic CNV is reviewed, along with a brief discussion of historical treatments. The pharmacology of the three most commonly used anti-VEGF agents is discussed, with an emphasis on the licensed drugs, ranibizumab and aflibercept. A comprehensive clinical approach to diagnosis and treatment of myopic CNV is presented. EXPERT OPINION: The current standard of care for myopic CNV is intravitreal inhibition of VEGF, with ranibizumab and aflibercept licensed for intraocular use. The diagnosis, OCT features of disease activity and retreatment algorithm for myopic CNV is different from wet age-related macular degeneration. In the long-term, myopic CNV may be associated with gradual, irreversible visual loss due to progressive chorioretinal atrophy, for which there is currently no treatment.

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.

Aflibercept Treatment for Neovascular Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy Refractory to Anti-vascular Endothelial Growth Factor.

PURPOSE: To report the results of switching treatment to vascular endothelial growth factor (VEGF) Trap-Eye (aflibercept) in neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) refractory to anti-VEGF (ranibizumab and bevacizumab). METHODS: This is a retrospective study involving 32 eyes from 29 patients; 18 were cases of neovascular AMD and 14 were cases of PCV. The best-corrected visual acuity (BCVA) and central macular thickness (CMT) of spectral-domain optical coherence tomography were evaluated. RESULTS: BCVA and CMT improved from 0.58 to 0.55 (p = 0.005) and from 404 to 321 µm (p < 0.001), respectively, after switching to aflibercept. The 14 eyes that received 6 or more aflibercept injections remained stable at 0.81 to 0.81 and 321 to 327 µm (p = 1.0, 0.29), respectively, after 3 aflibercept injections. The 10 eyes that received 3 or more bevacizumab injections after 3 or more aflibercept injections worsened, from 0.44 to 0.47 and from 332 to 346 µm (p = 0.06, 0.05), respectively. The results showed similar improvement of BCVA and CMT in neovascular AMD and PCV. CONCLUSIONS: Aflibercept seems to be effective for improvement and maintenance of BCVA and CMT for neovascular AMD and PCV refractory to anti-VEGF. Switching from aflibercept back to bevacizumab treatment may not be a proper strategy.

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.

Impact of visceral fat and pro-inflammatory factors on the pathogenesis of age-related macular degeneration.

PURPOSE: Previous studies have indicated that the immune system is involved in the pathogenesis of the AMD. Increased visceral fat, in addition, has a pro-inflammatory effect on the organism by producing or influencing different kinds of inflammatory factors. The aim of this study is to determine the relationship of body fat distribution in patients with age-related macula degeneration in comparison to a control group in the Austrian population. METHODS: In this case-control study, body weight and height, and body mass index (BMI) were measured for each subject in 54 patients with exudative AMD and compared to 46 gender- and age-matched healthy control subjects. Body composition and abdominal fat areas were measured using dual-energy X-ray absorptiometry (DEXA). Data on age, gender distribution, smoking history and systemic diseases, respectively, were compared. The inflammatory markers CRP, tumour necrosis factor-alpha (TNF-alpha), leptin, amyloid A, amyloid beta and interleukin-6 (IL-6) were assayed by ELISA (R&D). RESULTS: DEXA revealed central-abdominal-to-total body fat ratio of 0.073 +/- 0.011 in AMD patients compared to 0.061 +/- 0.013 in the controls (p <0.001; d = 0.98). The calculation of BMI has provided a significant result (p =0.045). U-test results for Aß1-42, IL-6, SAA and CRP each were significant (p < 0.05), with higher values in AMD patients. Leptin, TNF-alpha and Aß1-40 showed no significant differences between the groups. CONCLUSION: Our results suggest that abdominal fat distribution is significantly associated with age-related macular degeneration. Analysis of patients with exudative AMD revealed higher levels of CRP, amyloid ß1-42, IL-6 and amyloid alpha.

[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.

Omega-3 supplementation combined with anti-vascular endothelial growth factor lowers vitreal levels of vascular endothelial growth factor in wet age-related macular degeneration.

PURPOSE: To determine the influence of omega-3 supplementation on vitreous vascular endothelial growth factor A (VEGF-A) levels in patients with exudative age-related macular degeneration (wet AMD) receiving intravitreal anti-VEGF treatment. DESIGN: Prospective, randomized, open-label, single-center, clinical trial, consecutive interventional case series. METHODS: The study included 3 cohorts with wet AMD and a control group with epiretinal membrane or macular hole. Twenty wet AMD patients being treated with anti-VEGF were randomized to daily supplementation of antioxidants, zinc, and carotenoids with omega-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid; group 1, n = 10) or without omega-3 fatty acids (group 2, n = 10). They were compared with an anti-VEGF treatment-naïve wet AMD group (group 3, n = 10) and an epiretinal membrane or macular hole group (group 4, n = 10). Primary outcome was vitreal VEGF-A levels (at the time of anti-VEGF injection). Secondary outcomes were plasma VEGF-A and central foveal thickness. Patients with new submacular hemorrhage or any other treatment within 3 months were excluded. Final analyses included 9, 6, 7, and 8 patients in groups 1 through 4, respectively. RESULTS: Patients receiving omega-3s (group 1) had significantly lower levels of vitreal VEGF-A (141.11 ± 61.89 pg/mL) when compared with group 2 (626.09 ± 279.27 pg/mL; P = .036) and group 3 (735.48 ± 216.43 pg/mL; P = .013), but similar levels to group 4 (235.81 ± 33.99 pg/mL; P = .215). All groups showed similar values for plasma VEGF-A and central foveal thickness measurements. CONCLUSIONS: This study demonstrated that omega-3 supplementation combined with anti-VEGF treatment is associated with decreased vitreal VEGF-A levels in wet AMD patients.

Polypoidal choroidal vasculopathy and history of central serous chorioretinopathy.

PURPOSE: To evaluate the possible causative role of central serous chorioretinopathy (CSC) in the development of exudative age-related macular degeneration (AMD). METHODS: In a cross-sectional study at an institutional setting, 150 control subjects who had senile cataract or nasolacrimal duct stenosis and who were older than 50 years were enrolled. The background data for 89 patients with typical AMD (tAMD) and 138 patients with polypoidal choroidal vasculopathy (PCV) were used for comparison. Their medical records were taken for history of CSC, hypertension, systemic steroid use, and smoking. The fundus was also evaluated for signs of atrophic retinal pigment epithelial (RPE) tract and for focal photocoagulation scars in the macula. RESULTS: After adjusting for age, gender, and history of hypertension, systemic steroid use, and smoking, history of CSC was significantly more frequent (P<0.0001) in patients with PCV (15 patients, 10.9%) compared with patients with tAMD (2 patients, 2.2%) or control subjects (0 patients). On fundoscopy, an atrophic RPE tract (seven patients) or a focal photocoagulation scar (one patient) was observed only in patients with PCV (eight patients, 5.8%), and the frequency was statistically significant compared with that with tAMD (P=0.0143) or control subjects (P=0.0143). The laterality of CSC and AMD involved the same eye in 9 of 10 patients among those who had unilateral AMD and a reported unilateral CSC history. CONCLUSION: A history of CSC may be a predisposing factor for the development of PCV in the Japanese population.