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The treatment of neovascular (wet) age-related macular degeneration (AMD) with ranibizumab is now very well established in terms of efficacy and safety. Recent clinical trials and real-world studies have demonstrated the advantages of a Treat-and-Extend (T&E) regimen, and many hospital departments are now in the process of adopting this new regimen in favor of the pro re nata regimen for initiating and continuing ranibizumab therapy for patients with wet AMD. The comprehensive spectrum of issues related to implementation of the regimen is covered qualitatively in ten didactic topics provided by a group of clinicians with direct experience of this regimen in their department. The topics include definition, new and previously treated eyes, management of high-frequency injections, maximum extensions, discontinuing T&E, bilateral cases, clerical, audit, and patient counseling. This article aims to provide a useful resource for the implementation of the T&E regimen. A quantitative summary of the visual outcomes in key publications is also provided in this article. This article should be a valuable resource for staff training. [ABSTRACT FROM AUTHOR]

Purpose: To identify parameters from cone function and recovery after photostress that detect functional deficits in early non-exudative age-related macular degeneration (AMD) and to determine the repeatability of these parameters. Methods: Cone-mediated visual function recovery after photostress was examined in three groups of subjects: young normal subjects (ages 20–29; N=8), older normal subjects (ages 50–90; N=9), and early non-exudative AMD subjects (ages 50–90; N=12). Eight AMD and four normal subjects were retested 1 year after the initial evaluation. Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) and parameters of cone function (baseline cone sensitivity and cone recovery half-life following photobleach) were measured and compared between AMD and normal subjects. Short-term repeatability was assessed for each subject’s initial evaluation. Long-term repeatability was assessed by comparing outcomes from the initial evaluation and 1-year follow-up. Results: The mean baseline cone threshold was significantly worse in subjects with early AMD compared to older normal subjects (-1.80±0.04 vs -1.57±0.06 log cd/m2 p=0.0027). Moreover, the baseline cone threshold parameter exhibited good short-term (intraclass correlation coefficient [ICC]=0.88) and long-term (ICC=0.85) repeatability in all subjects. The cone intercept parameter and ETDRS VA were not significantly different between AMD and older normal subject groups. Cone recovery half-life was significantly different between older normal and AMD subject groups (p=0.041). Neither ETDRS VA nor cone function parameters were significantly different for any group at the 1-year follow-up. Conclusion: The baseline cone threshold shows potential as a novel parameter to assess visual dysfunction in early AMD. This outcome consistently detected deficits in AMD subjects, and differentiated them from age-matched controls with high test–retest repeatability. [ABSTRACT FROM AUTHOR]

Purpose: This pilot cross-sectional study aimed to determine age-related changes of the retinal nerve fiber layer (RNFL) thickness in retinal periphery by swept-source optical coherence tomography-based analysis. Methods: Forty eyes of 40 healthy subjects were studied in three age groups, group 1 (20-40 years, n=15), group 2 (41-60 years, n=14), and group 3 ($61 years, n=11). Wideangle swept-source optical coherence tomography scans, including the optic disc and macula, were montaged with the nasal peripheral optical coherence tomography images acquired with a contralateral gaze. The peripapillary and peripheral RNFL thickness values were obtained for nasal and temporal sides. The ratio of peripheral-to-peripapillary RNFL thickness was also calculated for these sectors. Results: We detected a significantly thinner RNFL in older than younger subjects at a distance of 6 mm from the optic disc on nasal and temporal sides (P<0.001). An age-related reduction in peripheral-to-peripapillary RNFL thickness ratios (P<0.001 and P<0.02 for nasal and temporal sides, respectively) was also detected. Conclusion: The age-related decline should be taken into consideration when determining the glaucoma-related alterations in peripheral RNFL thickness. Continued analysis in patients with ocular hypertension and glaucoma should help determine whether RNFL in the periphery with lower nerve tissue reserve might be more susceptible to injury, whether injury to the peripheral RNFL might be easier to detect, and/or whether analysis of the peripheral RNFL thickness could improve clinical diagnosis and follow-up of glaucoma. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the correlation between visual acuity and central macular thickness (CMT) and choroidal thickness (CCT) in patients with wet age-related macular degeneration (AMD). Methods: In this retrospective analysis, 14 eyes that received .10 ranibizumab injections (based on pro re nata [PRN] regimen) and maintained initial visual acuity gain were analyzed. The following 5 parameters were measured at the foveal center: CMT (distance from the inner limiting membrane [ILM] to Bruch's membrane); central retinal thickness (CRT; distance from the ILM to the inner limit of the retinal pigment epithelium or subretinal fluid [SRF]); SRF thickness (SRFT); pigment epithelium detachment thickness (PEDT); and CCT. The correlation between the logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) and the 5 parameters was examined with generalized estimating equations. Results: CMT, CRT, and CCT were negatively correlated with logMAR BCVA (P=0.031, 0.023, and 0.036, respectively) when only CMT values less than the thickness that maximized visual acuity for each eye were used for the analysis. Each 100-µm reduction in CMT, CRT, or CCT improved logMAR BCVA by -0.1, -0.08, or -0.07, respectively. SRFT and PEDT were not correlated with BCVA. The median CMT that maximized the visual acuity was 230 µm. Conclusion: Dry macula with CMT, 230 µm was associated with temporary decrease in visual acuity in AMD patients whose visual acuity was maintained with PRN regimen. [ABSTRACT FROM AUTHOR]

Purpose: The present study focused on the assessment of the mRNA levels of the insulin-like growth factor (IGF) family in patients with the exudative form of age-related macular degeneration (AMD) before and after ranibizumab intravitreal injections. Patients and methods: An analysis of the expression profile of the IGF family of genes in patients with AMD was carried out using the oligonucleotide microarray and quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) methods. Results: In the peripheral blood mononuclear cells (PBMCs) obtained from AMD group receiving ranibizumab compared to the peripheral blood mononuclear cells from AMD group before ranibizumab treatment using oligonucleotide microarray technique, six statistically significant differentially expressed transcripts related to the IGF family were detected (unpaired t-test, p<0.05, fold change .1.5). Moreover, analysis using the real-time RT-qPCR technique revealed statistically significant differences in the IGF2 and IGF2R mRNA levels (Mann-Whitney U test, p<0.05) between the two groups that were studied. Statistical analyses of both oligonucleotide microarray and real-time RT-qPCR results demonstrated a significant decreased expression only for IGF2 mRNA. Conclusion: Our results revealed a changed expression of IGF2 mRNA after ranibizumab treatment. [ABSTRACT FROM AUTHOR]

Background: Visual impairment in elderly people is a considerable health problem that significantly affects quality of life of millions worldwide. The magnitude of this issue is becoming more evident with an aging population and an increasing number of older individuals. Objective: The objective of this article was to review the clinical and pathological aspects of age-related macular degeneration (AMD), diagnostic tools, and therapeutic modalities presently available or underway for both atrophic and wet forms of the disease. Methods: An online review of the PubMed database was performed, searching for the key words. The search was limited to articles published since 1980 to date. Results: Several risk factors have been linked to AMD, such as age (.60 years), lifestyle (smoking and diet), and family history. Although the pathogenesis of AMD remains unclear, genetic factors have been implicated in the condition. Treatment for atrophic AMD is mainly close observation, coupled with nutritional supplements such as zinc and antioxidants, whereas treatment of wet AMD is based on targeting choroidal neovascular membranes. Conclusion: Identification of modifiable risk factors would improve the possibilities of preventing the progression of AMD. The role of anti-vascular endothelial growth factor (anti-VEGF) agents has transformed the therapeutic approach of the potentially blinding disease "wet AMD" into a more favorable outcome. [ABSTRACT FROM AUTHOR]

Background: Age-related macular degeneration (AMD) is a multifactorial degenerative ocular disease that leads to loss of central vision. Functional gene polymorphisms have already been associated with the disease (for example, ARMS2 A69S, rs10490924). Aim: The goal of our study was to verify the correlation of the aforementioned ARMS2 variation with the disease, to examine, for the first time, the role of the CD14 C260T variation (rs2569190), and to investigate the association of two TLR4 polymorphisms (Asp299Gly or rs4986790 and Thr399Ile or rs4986791) in a Greek population with the wet form of AMD. Patients and methods: Genomic DNAs were isolated from blood samples of 103 healthy controls and 120 Greek patients with wet AMD who were age- and sex-matched, and all of whom were clinically evaluated. For the genotyping of all selected polymorphisms, polymerase chain reaction–restriction fragment length polymorphism analysis was performed. Results and conclusions: This study confirmed the association between the ARMS2 variation and AMD, detecting the T risk allele in a significantly higher frequency in the patient group, compared with the control subjects (45% vs 29.13%, P< 0.001, odds ratio [OR] 1.99, confidence interval 1.34–2.95). For the CD14 polymorphism, no statistically significant correlation was observed. As for the TLR4 polymorphisms, the percentage of heterozygotes increased from 2.9% to 11.7% in the patient population for Asp299Gly and from 1.9% to 10% for the Thr399Ile polymorphism (ORs 4.40 [P=0.01] and 5.61 [P=0.0088], respectively). Although our ARMS2 and CD14 results provided definite conclusions, the role of innate immunity TLR4 gene awaits further investigation in larger AMD populations with more clinical data collected on past microbial infections. [ABSTRACT FROM AUTHOR]

Purpose: People with age-related macular degeneration (AMD) have difficulties in familiar face recognition and facial expression discrimination. Our aim was to evaluate the visual processing of faces in AMD patients and whether this would be improved by anti-vascular endothelial growth factor therapy. This was a prospective interventional cohort study. Patients: Twelve patients with monocular wet AMD and 6 control subjects were recruited. Face detection processes were studied using cortical event-related potentials (ERPs). Patients received 3 bevacizumab intravitreal injections to the single affected eye. At baseline and 4–6 weeks after the last injection, clinical presentation and ERPs of the face task were evaluated. Face pictures were shown as targets (16.7%) among standard pictures of pixelated faces in an oddball-type paradigm. Results: Face pictures elicited well-defined electrical components in occipital and parieto-occipital cortical areas at baseline and after treatment. The face-specific N170 component was evident in all subjects with longer peak latency in patients than in controls (170±13 vs 155±14, P=0.032). Unexpectedly, an early component reflecting unintentional prediction of perceiving a face, that is, deviance-related negativity, was present in patients and controls. Visual acuity of the affected eye seemed improved in patients from logarithm of the minimum angle of resolution 0.71 (±0.33) to 0.52 (±0.39) by 119 (±23) days without accompanying significant change in face-specific ERPs. Conclusions: Monocular wet AMD distinctly influenced face-specific brain electrophysiological components. However, the anti-vascular endothelial growth factor treatment did not improve the binocular face detection ability. The EudraCT number of this study is 2012-000765-20. [ABSTRACT FROM AUTHOR]

Purpose: Macular hole (MH) is part of a group of age-related degenerative diseases characterized by pathology of vitreomacular interface. Similarly, neovascular age-related macular degeneration (nAMD) affects older patients and is a leading cause of irreversible visual loss. The purpose of this case series is to describe the development of full-thickness MH in patients with nAMD, following antivascular endothelial growth factor (anti-VEGF) treatment. Methods: Participants in this case series were four patients with nAMD, who received anti-VEGF injections with variable therapeutic response to treatment. Patients were examined at baseline (when AMD was diagnosed) and monthly thereafter. The examination included visual acuity measurement, slit-lamp biomicroscopy, and optical coherence tomography. Results: All patients were found to develop full-thickness MH within 1-4 months after the last anti-VEGF injection, even in the absence of pre-existing vitreomacular interface abnormalities in some cases. The median number of injections before the MH formation was 3. Conclusion: MH formation may represent an adverse effect of anti-VEGF treatment in patients with nAMD and could be also coexisting pathology with nAMD in older individuals. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to study the prevalence and characteristics of idiopathic polypoidal choroidal vasculopathy (IPCV) in Thai patients with clinical and angiographic choroidal neovascularization (CNV). Patients and methods: A consecutive case study of 140 patients presenting with CNV was conducted in nine large referral eye centers throughout Thailand. The demographic data, fundus photographs, fundus fluorescein angiography and indocyanine green angiography of the patients were analyzed. Results: Of 129 patients with clinical and angiographic CNV, IPCV was diagnosed in 100 patients (77.52%), idiopathic CNVs in 16 patients (12.40%) and age-related macular degeneration (AMD) in 12 patients (9.30%). Of the 107 eyes with IPCV, 90 eyes (84.11%) had both branching venous networks (BVNs) and polypoidal lesions. Most IPCV patients (93%) had unilateral involvement and were at a younger age than AMD patients. In all, 79 eyes (73.83%) had lesions found in the macular area, 14 eyes (13.08%) in the temporal to vascular arcades, ten eyes (9.35%) in the peripapillary area and four eyes (3.74%) in both macular and peripapillary areas. The clinical manifestations of IPCV at presentation were categorized into two patterns. There were 95 eyes (88.79%) of a hemorrhagic pattern and 12 eyes (11.21%) of an exudative pattern. Conclusion: IPCV is the most common macular disease in Thai patients with CNV. Most IPCVs have both BVNs and polypoidal lesions located in the macular area and present with a hemorrhagic pattern. [ABSTRACT FROM AUTHOR]

Background: Individuals with neovascular age-related macular degeneration (AMD) have altered number and distribution of retinal macrophages and show changes in circulating antibodies. We wanted to investigate the corresponding precursors, with subpopulations. We therefore measured monocyte and B-lymphocyte populations in individuals with neovascular AMD. Design: This was an observational case-control study. Participants or samples: A total of 31 individuals with neovascular AMD and 30 healthy age-matched controls were included. Methods: Patients and controls were interviewed, and ophthalmological examination included visual acuity assessment using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, spectral domain optical coherence tomography (SD-OCT), slit-lamp examination and fundus photography. Moreover, venous blood was drawn and prepared for flow cytometry. Cells were gated and measured for surface markers. Main outcome measures: Relative amounts of monocytes and B-lymphocytes with subsets, as well as selected surface markers, were measured. Results: The two groups did not significantly differ in age, smoking history, body mass index, physical activity or C-reactive protein (CRP). Total monocytes (percentage of all leukocytes) were lower in the neovascular AMD group (median 5.5%) compared with the level in the control group (6.5%; P-value: 0.028). The percentage of intermediate monocytes positive for cluster of differentiation 11b (CD11b) was lower for AMD patients (99.4%) compared with 100% for the control group (P-value: 0.032). Conclusion: We observed lower numbers of monocytes, which show a potentially impaired ability to migrate across the endothelial wall in patients with neovascular AMD. These subtle changes could potentially lead to an imbalance in the recruitment of macrophages into the retina during disease development. [ABSTRACT FROM AUTHOR]

Purpose: Alpha lipoic acid (ALA) is an antioxidant and iron-chelating supplement that has potential benefits for geographic atrophy in dry age-related macular degeneration as well as other eye diseases. The purpose of this study was to determine the tolerability of ALA in the elderly population. Patients and methods: Fifteen subjects, age $65 years, took sequential ALA doses of 600, 800, and 1,200 mg. Each dose was taken once daily with a meal for 5 days. After each dose was taken by the subjects for 5 days, the subjects were contacted by phone, a review of systems was performed, and they were asked if they thought they could tolerate taking that dose of ALA for an extended period of time. Results: The 600 mg dose was well tolerated. At the 800 mg dose, one subject had an intolerable flushing sensation. At the 1,200 mg dose, two subjects had intolerable upper gastrointestinal side effects and one subject had an intolerable flushing sensation. Subjects taking gastrointestinal prophylaxis medications had no upper gastrointestinal side effects. Conclusion: High-dose ALA is not completely tolerated by the elderly. These preliminary data suggest that gastrointestinal prophylaxis may improve tolerability. (ClinicalTrials.gov, NCT02613572). [ABSTRACT FROM AUTHOR]

Purpose: To compare the effects of intravitreal ranibizumab in monotherapy (group A) and combined with photodynamic therapy (PDT) with verteporfin (group B) in retinal angiomatous proliferation (RAP) treatment. Methods: This was a multicentric, prospective, randomized clinical study conducted with parallel groups. The study eye in both groups received ranibizumab on days 1, 30, and 60 (loading dose); group B received PDT additionally on day 1. Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) testing and optical coherence tomography were performed monthly, and fluorescein angiography and indocyanine green angiography were performed quarterly. Retreatment criteria were leakage in fluorescein angiography or indocyanine green angiography, mean foveal thickness increase $100 μm, or VA decrease $5 letters. Results: Twenty patients were recruited (ten patients in each group). Six eyes had previous treatment (three eyes in group A and three eyes in group B), so only 14 eyes were naïve. At 12-month follow-up, mean VA improved +1.5 letters in group A and +5.6 letters in group B (analysis of variance test; P.0.05). Two patients (20%) in both groups gained $15 letters (chi-square test; P.0.05). Mean changes in greatest linear dimension and in foveal thickness were not statistically significant between groups of treatment (analysis of variance test; P.0.05). Mean retreatments per patient were 1.8 (group A) and 0.9 (group B) (Mann-Whitney U-test; P.0.05). One patient died due to underlying disease not related to study medication. Conclusion: Intravitreal ranibizumab administered in monotherapy or combined with PDT was efficacious in terms of VA stabilization in patients with RAP. [ABSTRACT FROM AUTHOR]

Objective: To describe the 1-year efficacy of aflibercept in Japanese patients with age-related macular degeneration (AMD) who were resistant to ranibizumab treatment. Design: Retrospective case series. Participants: Fourteen consecutive eyes of 14 patients with AMD were enrolled who had no substantial response or developed resistance to intravitreal ranibizumab injections. Methods: All patients were subcategorized into one of two subtypes of AMD: seven patients with occult choroidal neovascularization (CNV) and seven with polypoidal choroidal vasculopathy (PCV). Serial intravitreal aflibercept (IVA) injections were administered. Comprehensive ophthalmic examinations, including optical coherence tomography, were conducted at baseline and at follow-up examinations at 1, 3, 6, and 12 months after the initial IVA injection. The bestcorrected visual acuity converted to logarithm of the minimum angle of resolution (logMAR) and central macular thickness (CMT) at each follow-up visit were compared with the baseline values. The anatomic response was also assessed with absorption or reduction of fluid in the subretina or subretinal pigment epithelial space. Results: The logMAR best-corrected visual acuity improved significantly at 3, 6, and 12 months in the total cohort: at 3 and 6 months in patients with occult CNV and at 3 and 12 months in patients with PCV. The CMT decreased significantly at all follow-up visits in the total cohort as well as in both subtypes, except for the CMT at 6 months in PCV patients. The anatomic improvement was also demonstrated in all cases, and pigment epithelial detachments tended to be resolved more rapidly in patients with PCV than in patients with occult CNV. Conclusion: Conversion to IVA was effective in patients with AMD resistant to ranibizumab, showing rapid morphologic improvement. The logMAR visual acuity was raised significantly within 12 months, and the clinical course of visual acuity improvement may differ according to the AMD subtypes. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to assess the impact of daily oral supplementation with Macushield (10 mg/d meso-zeaxanthin, 10 mg/d lutein, and 2 mg/d zeaxanthin) on eye health in patients with retinal diseases by assessing the macular pigment (MP) profile, the visual function, and the quality of life. Methods: Fifty-one patients with various retinal diseases were supplemented daily and followed up for 6 months. The MP optical density was measured using the customized heterochromatic flicker photometry and dual-wavelength autofluorescence. Visual function was evaluated by assessing the change in best corrected visual acuity, contrast sensitivity, and glare sensitivity in mesopic and photopic conditions. Vision-related and general quality of life changes were determined using the National Eye Insititute-Visual Function Questionnaire-25 (NEI-VFQ-25) and EuroQoL-5 dimension questionnaires. Results: A statistically significant increase in the MP optical density was observed using the dual-wavelength autofluorescence (P=0.04) but not with the customized heterochromatic flicker photometry. Statistically significant (P<0.05) improvements in glare sensitivity in low and medium spatial frequencies were observed at 3 months and 6 months. Ceiling effects confounded other visual function tests and quality of life changes. Conclusion: Supplementation with the three carotenoids enhances certain aspects of visual performance in retinal diseases. [ABSTRACT FROM AUTHOR]

Background: To evaluate the effect of photodynamic therapy (PDT) using a modified procedure on exudative age-related macular degeneration having been conventionally difficult to treat. Methods: The medical records of eight consecutive patients (eight eyes) with age-related macular degeneration treated with modified PDT were reviewed retrospectively. Modified PDT was used for the lesions that could not be covered by conventional use of PDT, either because the lesion was too large or too close to the optic disc. A moving PDT laser spot at constant speed, for 83 seconds, was used to cover the entire lesion, and was named "Ironing PDT." This retrospective study was performed with informed patient consent. It was approved by the Institutional Review Board of Kansai Medical University. Results: No exudation could be found 36 months after treatment in five eyes (62.5%). There was no significant difference between the best-corrected visual acuity before PDT (0.95 logMAR) and after PDT (1.09 logMAR). The logMAR best-corrected visual acuity was improved in one eye, maintained in five eyes, and deteriorated in two eyes. Conclusion: Ironing PDT decreased subfoveal fluid and preserved visual acuity in some patients with age-related macular degeneration difficult to treat with conventional therapy. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the 5-year results obtained in clinical practice in the treatment of neovascular age-related macular degeneration (nAMD) with anti-VEGF agents. Materials and methods: We retrospectively analyzed all patients with nAMD who initiated anti-VEGF treatment before October 2009. We collected data regarding visual and anatomical outcomes. Results: A total of 278 patients met the selection criteria. The mean number of intravitreal injections was 5.7 in the first year and 3.7 in the fifth year. A positive mean visual acuity variation of +3.7 Early Treatment Diabetic Retinopathy Study letters occurred in the first year, but no significant differences relative to baseline were observed thereafter. The majority of patients (71%) maintained stable visual acuity throughout follow-up. At 5 years, mean central macular thickness remained substantially inferior to baseline (-96.6 µm), and 56% of patients maintained dry retinas. Conclusion: Anti-VEGF therapy leads to long-term visual stabilization in the great majority of patients. [ABSTRACT FROM AUTHOR]

Purpose: Telomere attrition and corresponding cellular senescence of the retinal pigment epithelium contribute to the changes of age-related macular degeneration. Activation of the enzyme telomerase can add telomeric DNA to retinal pigment epithelium chromosomal ends and has been proposed as a treatment for age-related macular degeneration. We report the use of a small molecule, oral telomerase activator (TA)-65 in early macular degeneration. This study, focusing on early macular degeneration, provides a model for the use of TAs in age-related disease. Method: Thirty-eight (38) patients were randomly assigned to a 1-year, double-blinded, placebo-controlled interventional study with arms for oral TA-65 or placebo. Macular functions via micro-perimetry were the primary measured outcomes. Results: The macular function in the arm receiving the TA-65 showed significant improvement relative to the placebo control. The improvement was manifest at 6 months and was maintained at 1 year: macular threshold sensitivity (measured as average dB [logarithmic decibel scale of light attenuation]) improved 0.97 dB compared to placebo (P-value 0.02) and percent reduced thresholds lessened 8.2% compared to the placebo arm (P-value 0.04). Conclusion: The oral TA significantly improved the macular function of treatment subjects compared to controls. Although this study was a pilot and a larger study is being planned, it is noteworthy in that it is, to our knowledge, the first randomized placebo-controlled study of a TA supplement. [ABSTRACT FROM AUTHOR]

Purpose: AURA was an international, retrospective, observational study that monitored the real-life use and effectiveness of ranibizumab injections in patients with neovascular age-related macular degeneration (nAMD). This paper reports the findings from the UK. Methods: Patients who started treatment with ranibizumab between January 1, 2009, and August 31, 2009, and had documented follow-up to the end of their treatment and/or monitoring or until August 31, 2011, were retrospectively monitored; the diagnosis and subsequent decision to treat was made by the patient's own physician. Assessments included the change in visual acuity (standardized letter count) during the first and second years after start of ranibizumab therapy and resource utilization. Results: Four hundred and ten patients from 13 UK centers were analyzed. The mean (standard deviation [SD]) letter score at baseline was 55.0 (17.8). The mean (SD) change in visual acuity from baseline was +6.0 (15.4) letters at year 1 and +4.1 (16.9) at year 2. Most of the patients (86.6%) completed a 3-month loading phase; the visual improvements were numerically higher in these patients. Over 2 years, the mean (SD) number of clinic visits and injections was 18.4 (5.0) and 9.0 (4.7), respectively. Resource use and visual acuity gains were greater than those observed in the global population, which included other countries enrolled in AURA (Canada, France, Germany, Ireland, Italy, the Netherlands, and Venezuela). When patients were stratified according to severity of nAMD (based on letter count at baseline), the mean change in visual acuity score at years 1 and 2 was also higher for the UK than for the global population across all subgroups. Conclusion: Monitoring and treatment rates were high in the UK, resulting in better visual acuity outcomes compared with other included countries. This suggests that translation of clinical study outcomes into real-life settings is achievable, but at the expense of higher resource utilization than is currently the norm in most developed countries. [ABSTRACT FROM AUTHOR]

Geographic atrophy (GA) of the retinal pigment epithelium (RPE) is a devastating complication of age-related macular degeneration (AMD). GA may be classified as drusenrelated (drusen-associated GA) or neovascularization-related (neovascular-associated GA). Drusen-related GA remains a large public health concern due to the burden of blindness it produces, but pathophysiology of the condition is obscure and there are no proven treatment options. Genotyping, cell biology, and clinical imaging point to upregulation of parainflammatory pathways, oxidative stress, and choroidal sclerosis as contributors, among other factors. Onset and monitoring of progression is accomplished through clinical imaging instrumentation such as optical coherence tomography, photography, and autofluorescence, which are the tools most helpful in determining end points for clinical trials at present. A number of treatment approaches with diverse targets are in development at this time, some of which are in human clinical trials. Neovascular-associated GA is a consequence of RPE loss after development of neovascular AMD. The neovascular process leads to a plethora of cellular stresses such as ischemia, inflammation, and dramatic changes in cell environment that further taxes RPE cells already dysfunctional from drusen-associated changes. GA may therefore develop secondary to the neovascular process de novo or preexisting drusen-associated GA may continue to worsen with the development of neovascular AMD. Neovascular-associated GA is a prominent cause of continued vision loss in patients with otherwise successfully treated neovascular AMD. Clearly, treatment with vascular endothelial growth factor (VEGF) inhibitors early in the course of the neovascular disease is of great clinical benefit. However, there is a rationale and some suggestive evidence that anti-VEGF agents themselves could be toxic to RPE and enhance neovascularassociated GA. The increasing prevalence of legal blindness from this condition due to the aging of the general population lends urgency to the search for a therapy to ameliorate GA. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of monthly injections of aflibercept and ranibizumab on foveal structure after three months, for the treatment of occult choroidal neovascularization (CNV) in age-related macular degeneration (AMD). Methods: We retrospectively studied 103 eyes with treatment-naïve neovascular AMD with occult and no classic CNV. Seventy-four of 103 eyes were treated with ranibizumab (intravitreal ranibizumab injection [IVR] group); 29 eyes were treated with aflibercept (intravitreal aflibercept injection [IAI] group). The best-corrected visual acuity and the retinal and choroidal structure at the fovea were evaluated using optical coherence tomography. Results: The total foveal thickness, the height of serous retinal detachments, and subfoveal choroidal thickness were compared with baseline, and the incidence of retinal pigment epithelial elevation significantly decreased in the IAI group compared with the IVR group. In contrast, the thickness of the sensory retina at the fovea significantly decreased in the IVR group when compared with the IAI group. The logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity improved more significantly in the IVR group (-0.085±0.164) than in the IAI group (-0.020±0.125) at 3 months (P=0.017). Conclusion: After intravitreal injection, aflibercept more rapidly reduced subretinal fluid and subfoveal choroidal thickness. In contrast, ranibizumab decreased the sensory retinal thickness compared with aflibercept. The responses of the retinal and choroidal tissue to these anti-VEGF agents may be different during the induction phase for eyes with occult CNV secondary to neovascular AMD. [ABSTRACT FROM AUTHOR]

Objective: To study the efficacy of epiretinal membrane (ERM) peeling in eyes with dry agerelated macular degeneration (AMD). Methods: We retrospectively analyzed patient charts on 17 eyes (16 patients) that underwent ERM peeling with a concurrent diagnosis of dry AMD. Results: Eyes with concurrent dry AMD and with a good preoperative best-corrected visual acuity (BCVA) (better than or equal to 20/50) had a statistically significant mean BCVA improvement at 6 months after ERM peeling. There was a statistical increase in mean BCVA from 20/95 to 20/56 in dry AMD eyes, and no eyes showed worsening in BCVA at 6 months or at most recent follow-up. Five/seventeen (29.4%) eyes had cataract formation or progression. There were no other complications, reoperations, or reoccurrences. Conclusion: ERM peeling in eyes with dry AMD may show significant improvement, especially in eyes with good preoperative BCVA. The procedure is relatively safe with low complications and reoccurrences. [ABSTRACT FROM AUTHOR]

Purpose: To report the 12-month outcomes of a patient switching from intravitreal ranibizumab to aflibercept for choroidal neovascularization (CNV) associated with angioid streaks (AS).Results: A 42-year-old Caucasian female with CNV associated with AS underwent intensive treatment with ranibizumab without significant functional or anatomic change. Treatment was then switched to aflibercept and the patient received the proposed age-related macular degeneration treatment regimen. After 3 loading doses of aflibercept, best-corrected visual acuity (BCVA) improved from 3/10 to 6/10, while optical coherence tomography (OCT) demonstrated resolution of the subretinal fluid with a reduction of the intraretinal fluid. After 12 months and 7 intravitreal injections of aflibercept, BCVA returned to 3/10, while OCT had demonstrated further morphologic improvement.Conclusion: Our case shows that aflibercept may be an alternative treatment for advanced cases of CNV associated with AS that respond insufficiently to ranibizumab injections. Prospective studies are required to further evaluate the effect of aflibercept and to propose a standardized treatment protocol for this entity. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to evaluate the long-term results of an implantable miniature telescope (IMT) in patients with bilateral, end-stage, age-related macular degeneration (AMD). Methods: A prospective, open-label, multicenter clinical trial with fellow eye controls enrolled 217 patients (mean age 76 years) with AMD and moderate-to-profound bilateral central visual acuity loss (20/80-20/800) resulting from untreatable geographic atrophy, disciform scars, or both. A subgroup analysis was performed with stratification for age (patient age 65 to <75 years [group 1; n=70] and patient age ≥75 years [group 2; n=127]), with a comparative evaluation of change in bestcorrected distance visual acuity (BCDVA), quality of life, ocular complications from surgery, adverse events, and endothelial cell density (ECD). Follow-up in an extension study was 60 months. Results: Data were available for 22, 38, and 31 patients in group 1 and 42, 46, and 32 patients in group 2 at 36, 48, and 60 months, respectively. Mean BCDVA improvement from baseline to 60 months was 2.41±2.69 lines in all patients (n=76), with 2.64±2.55 lines in group 1 and 2.09±2.88 lines in group 2. Quality of life scores were significantly higher in group 1. The most common significant surgery-related ocular complications in group 1 were iritis >30 days after surgery (7/70; 10%) and persistent corneal edema (3/70; 4.3%); and in group 2 were a decrease in BCDVA in the implanted eye or IMT removal (10/127 each; 7.9%), corneal edema >30 days after surgery (9/127; 7.1%), and persistent corneal edema (6/127; 4.7%). Significant adverse events included four corneal transplants, comprising two (2.9%) in group 1 and two (1.6%) in group 2. At 60 months, one patient in group 1 (3.2%) and three patients in group 2 (9.4%) had lost ≥2 lines of vision. The IMT was removed in one (1.4%) and ten (7.9%) patients in group 1 and group 2, respectively. Mean ECD loss was 20% at 3 months. Chronic loss was 3% per year. ECD loss was less in group 1 than in group 2 (35% versus 40%, respectively) at 60 months. Conclusion: Long-term results show substantial retention of improvement in BDCVA. Chronic ECD loss was consistent with that reported for conventional intraocular lenses. The IMT performed as well in group 1 (the younger group) as it did in group 2 through month 60. Younger patients retained more vision than their older counterparts and had fewer adverse events. Although not a specified outcome for this study, patients younger than 65 years also fared better than those in group 2 and retained more vision with fewer adverse events through month 60. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the prevalence of scleral hyaline plaque among older adults in the city of Niterói in southeastern Brazil. A second goal was to assess the correlation between scleral hyaline plaque and several age-related diseases, including eye diseases and systemic diseases. Methods: The study sample comprised 667 participants who were followed for 15 months. The study had a prospective, longitudinal, observational design that established inclusion and exclusion criteria. The following variables were selected for correlation with scleral hyaline plaque: sex, age, age range, iris color, ethnicity, presence of cataract, moderate to high myopia, age-related macular degeneration (AMD), diabetes mellitus, systemic arterial hypertension, degenerative arthritis, and osteoporosis. These correlations were assessed by means of the X2 test and Student's t-test. Multivariate analysis was performed to exclude factors that were potentially associated with aging exclusively but that did not have a direct relationship with hyaline plaque. Binary logistic regression was used to calculate odds ratios, significance, and confidence intervals. Results: Scleral hyaline plaques were found in 177 patients (17.54%). There was a statistically significant association between the presence of hyaline plaques and sex (female), age range (≥70 years old), ethnicity (Caucasian), cataract, moderate to high myopia, systemic arterial hypertension, degenerative arthritis, and osteoporosis (P<0.05). On multivariate binary logistic regression analysis, only female sex, age range (≥70 years), moderate to high myopia, and degenerative arthritis exhibited significant correlation. Conclusion: The prevalence of scleral hyaline plaque in the present study was higher than in previous reports in the medical literature. Several age-related diseases exhibited a correlation with scleral hyaline plaque. The most significant factors associated with scleral hyaline plaque were advanced age, female sex, moderate to high myopia, and degenerative arthritis. [ABSTRACT FROM AUTHOR]

Purpose: To investigate regulatory T cells (Tregs) and subsets of the Treg population in patients with neovascular age-related macular degeneration (AMD). Patients and methods: Twenty-one neovascular AMD cases and 12 age-matched controls without retinal pathology were selected. Patients were recruited from our outpatient retinal clinic. Control individuals were typically spouses. The diagnosis of neovascular AMD was confirmed using fluorescein and indocyaningreen angiography. Fresh venous blood was analyzed by flow cytometry using fluorochrome-conjugated antibodies to the Treg surface antigens CD4, CD25, CD127, CD45RA, and CD31. Main outcome measures were the percentage of CD25highCD127low Tregs, the percentage of CD45RA+ naïve Tregs, and the percentage of CD31+ recent thymic emigrant Tregs. Results: Comparing patients with neovascular AMD to controls, no significant differences were found in the percentages of CD4+ lymphocytes, CD25highCD127low Tregs, CD45RA+ naïve Tregs, or CD31+ recent thymic emigrant Tregs. Conclusion: Our data does not indicate an altered state of systemic Treg cells in neovascular AMD. [ABSTRACT FROM AUTHOR]

Contemporary management of neovascular age-related macular degeneration (AMD) has evolved significantly over the last few years. The goal of treatment is shifting from merely salvaging vision to maintaining a high quality of life. There have been significant breakthroughs in the identification of viable drug targets and gene therapies. Imaging tools with near-histological precision have enhanced our knowledge about pathophysiological mechanisms that play a role in vision loss due to AMD. Visual, social, and vocational rehabilitation are all important treatment goals. In this review, evidence from landmark clinical trials is summarized to elucidate the optimum modern-day management of neovascular AMD. Therapeutic strategies currently under development, such as gene therapy and personalized medicine, are also described. [ABSTRACT FROM AUTHOR]

A correction to the article "Effects intravitreal ranibizumab on the untreated eye and systemic gene expression profile in age-related macular degeneration" in the previous issue is presented.