Untreated Age-related Macular Degeneration Research Articles

Effects of Humanin G (HNG) on angiogenesis and neurodegeneration markers in Age-related Macular Degeneration (AMD)

Advanced stages of Age-related Macular Degeneration (AMD) are characterized by retinal neurodegeneration and aberrant angiogenesis, and mitochondrial dysfunction contributes to the pathogenesis of AMD. In this study, we tested the hypothesis that Humanin G (HNG), a cytoprotective mitochondrial-derived peptide, positively regulates cell proliferation, cell death, and the protein levels of angiogenesis and neurodegeneration markers, in normal (control) and AMD RPE transmitochondrial cybrid cell lines. These normal and AMD RPE transmitochondrial cybrid cell lines had identical nuclei derived from mitochondria-deficient ARPE-19 cell line, but differed in mitochondrial DNA (mtDNA) content that was derived from clinically characterized AMD patients and normal (control) subjects. Cell lysates were extracted from untreated and HNG-treated AMD and normal (control) cybrid cell lines, and the Luminex XMAP multiplex assay was used to examine the protein levels of angiogenesis and neurodegeneration markers. Humanin G reduced Caspase-3/7-mediated apoptosis, improved cell proliferation, and normalized the protein levels of angiogenesis and neurodegeneration markers in AMD RPE cybrid cell lines, thereby suggesting Humanin G's positive regulatory role in AMD.

Effect of Humanin G (HNG) on inflammation in age-related macular degeneration (AMD).

Inflammation plays a crucial role in the etiology and pathogenesis of AMD (Age-related Macular Degeneration). Humanin G (HNG) is a Mitochondrial Derived Peptide (MDP) that is cytoprotective in AMD and can protect against mitochondrial and cellular stress induced by damaged AMD mitochondria. The goal of this study was to test our hypothesis that inflammation-associated marker protein levels are increased in AMD and treatment with HNG leads to reduction in their protein levels. Humanin protein levels were measured in the plasma of AMD patients and normal subjects using ELISA assay. Humanin G was added to AMD and normal (control) cybrids which had identical nuclei from mitochondria-deficient ARPE-19 cells but differed in mitochondrial DNA (mtDNA) content derived from clinically characterized AMD patients and normal (control) subjects. Cell lysates were extracted from untreated and HNG-treated AMD and normal cybrids, and the Luminex XMAP multiplex assay was used to measure the levels of inflammatory proteins. AMD plasma showed reduced Humanin protein levels, but higher protein levels of inflammation markers compared to control plasma samples. In AMD RPE cybrid cells, Humanin G reduced the CD62E/ E-Selectin, CD62P/ P-Selectin, ICAM-1, TNF-α, MIP-1α, IFN–γ, IL-1β, IL-13, and IL-17A protein levels, thereby suggesting that Humanin G may rescue from mtDNA-mediated inflammation in AMD cybrids. In conclusion, we present novel findings that: A) show reduced Humanin protein levels in AMD plasma vs. normal plasma; B) suggest the role of inflammatory markers in AMD pathogenesis, and C) highlight the positive effects of Humanin G in reducing inflammation in AMD.

Novel approach to antiangiogenic factors in age-related macular degeneration therapy.

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among the population above 85 worldwide. There are two main types of AMD: neovascular and dry AMD. Neovascular AMD leads to macular changes resulting from abnormal choroidal neovascularization. Untreated neovascular AMD leads to scar formation and irreversible sight deterioration. Dry AMD in consequence leads to atrophic changes of the macula.The last decades brought a breakthrough in the therapy of neovascular age-related macular degeneration by introduction of, firstly, photodynamic therapy and, later, anti-VEGF agents administered intravitreally in order to stop neoangiogenesis. However, the treatment of dry AMD is still challenging. Among the directions in dry AMD treatment, the most promising are complement cascade inhibitors and complement cascade targeted gene therapy.In the article we outline the main directions in up-to-date experimental and practical approaches to wet and dry AMD therapy with the emphasis on antiangiogenic factors and gene therapy focused on the inhibition of pathological angiogenesis.

Automated classification of retinal images into AMD/non-AMD Class—a study using multi-threshold and Gassian-filter enhanced images

Eye is an essential sensory organ in human physiological system and disease in eye severely affects the vision system. Age-related-macular-degeneration (AMD) is a common eye disease in elderly people (age > 60 years) and the untreated AMD will cause severe eye illness including permanent vision loss. This research work proposes a machine-learning-system (MLS) to detect the AMD using the fundus-retinal-images. The various phases of the MLS employed in the proposed work is as follows; (i) Image thresholding based on Shannon’ Entropy and Bat Algorithm (BA + SE), (ii) Gaussian-filter (GF) based image smoothening, (iii) feature extraction, (iv) Feature selection using statistical test, and (v) classifier implementation and validation. The image features, such as the gray level co-occurrence matrix and entropies are considered to categorize the retinal image database into AMD/Non-AMD class. The performance of classifiers, such as Naive–Bayes (NB), decision-tree (DT), K-nearest neighbors, random-forest (RF) and support-vector-machine with linear kernel (SVM) are compared and the experimental outcome confirms that, the classification accuracy of SVM is superior (> 93%) compared to other classifiers.

Differential effects of risuteganib and bevacizumab on AMD cybrid cells

PurposeIntravitreal injections of anti-vascular endothelial growth factor (VEGF) treatments are currently used to treat wet age-related macular degeneration (AMD), diabetic retinopathy, and macular edema. Chronic, repetitive treatments with anti-VEGF may have unintended consequences beyond the inhibition of angiogenesis. Most recently, clinical trials have been conducted with risuteganib (RSG, Luminate®), which is anti-angiogenic and has neuroprotective and anti-inflammatory properties. Mitochondrial damage and dysfunction play a major role in development of AMD. Transmitochondrial cybrids are cell lines established by fusing human retinal pigment epithelial (RPE) cells that are Rho0 (lacking mtDNA) with platelets isolated from AMD subjects or age-matched normal subjects. Cybrid cell lines have identical nuclei but mitochondria from different subjects, enabling investigation of the functional consequences of damaged AMD mitochondria. The present study compares the responses of AMD cybrids treated with bevacizumab (Bmab, Avastin®) versus risuteganib (RSG, Luminate®). MethodsCybrids were created by fusing mtDNA depleted ARPE-19 cells with platelets from AMD or age-matched normal patients. AMD (n = 5) and normal (n = 3) cybrids were treated for 48 h with or without 1x clinical dose of 1.25 mg/50 μl (25,000 μg/ml) of Bmab or 1.0 mg/50 μl (20,000 μg/ml) of RSG. Cultures were analyzed for levels of cleaved caspase 3/7 and NucLight Rapid Red staining (IncuCyte® Live Cell Imager), mitochondrial membrane potential (ΔΨm, JC1 assay) or reactive oxygen species (ROS, H2DCFDA assay). Expression levels of genes related to the following pathways were analyzed with qRT-PCR: Apoptosis (BAX, BCL2L13, CASP-3, -7, -9); angiogenesis (VEGFA, HIF1α, PDGF); integrins (ITGB-1, -3, -5, ITGA-3, -5, -V); mitochondrial biogenesis (PGC1α, POLG); oxidative stress (SOD2, GPX3, NOX4); inflammation (IL-6, -18, -1β, IFN-β1); and signaling (P3KCA, PI3KR1). Statistical analyses were performed using GraphPad Prism software. ResultsThe untreated AMD cybrids had significantly higher levels of cleaved caspase 3/7 compared to the untreated normal cybrids. The Bmab-treated AMD cybrids showed elevated levels of cleaved caspase 3/7 compared to untreated AMD or RSG-treated AMD cybrids. The Bmab-treated cybrids had lower ΔΨm compared to untreated AMD or RSG-treated AMD cybrids. The ROS levels were not changed with Bmab or RSG treatment. Results showed that Bmab-treated cybrids had higher expression levels of inflammatory (IL-6, IL1-β), oxidative stress (NOX4) and angiogenesis (VEGFA) genes compared to untreated AMD, while RSG-treated cybrids had lower expression levels of apoptosis (BAX), angiogenesis (VEGFA) and integrin (ITGB1) genes. ConclusionsThese data suggest that the mechanism(s) of action of RSG, an integrin regulator, and Bmab, a recombinant monoclonal antibody, affect the AMD RPE cybrid cells differently, with the former having more anti-apoptosis properties, which may be desirable in treating degenerative ocular diseases.

Effects of bevacizumab, ranibizumab, and aflibercept on phagocytic properties in human RPE cybrids with AMD versus normal mitochondria

PurposeA critical biological function of retina pigment epithelium (RPE) cells is phagocytosis of photoreceptor outer segment (POS) disc membranes. Mitochondrial damage and dysfunction are associated with RPE cells of age-related macular degeneration (AMD) retinas. In this study, we use a transmitochondrial cybrid model to compare the phagocytic properties of RPE cells that contain AMD mitochondria versus age-matched normal mitochondria and their response to treatment with anti-vascular endothelial growth factor (VEGF) drugs: bevacizumab, ranibizumab, and aflibercept. MethodsCybrids, which are cell lines with identical nuclei but mitochondria (mt) from different subjects, are created by fusing mtDNA depleted ARPE-19 cells with platelets from AMD or age-matched normal patients. AMD (n = 5) and normal (n = 5) cybrids were treated with 1 μm fluorescent latex beads (1.52 × 107 beads/mL) and either 2.09 μM of bevacizumab, 2.59 μM of ranibizumab, or 5.16 μM of aflibercept. These doses of anti-VEGF drugs are equivalent to intravitreal injections given to AMD patients with choroidal neovascularization. Flow cytometry was performed using the ImageStreamX Mark II to assess phagocytic bead-uptake. The average fold values for bead-uptake and SEM were calculated using GraphPad Prism software. ResultsNormal cybrids showed decreased bead-uptake with a fold value of 0.65 ± 0.103 (p = 0.01) after treatment with bevacizumab, 0.80 ± 0.034 (p = 0.0003) with ranibizumab, and 0.81 ± 0.053 (p = 0.007) with aflibercept compared to the untreated normal cybrids (baseline fold of 1). The bevacizumab-treated, ranibizumab-treated, and aflibercept-treated AMD cybrids had decreased bead-uptake with a fold value of 0.71 ± 0.061 (p = 0.001), 0.70 ± 0.101 (p = 0.02), and 0.74 ± 0.125 (p = 0.07), respectively, compared to the untreated AMD cybrids (baseline fold of 1). ConclusionsOur initial findings showed that when treated with bevacizumab and ranibizumab, both AMD cybrids and age-matched normal cybrids had a significant decrease in bead-uptake. A similar decrease in bead-uptake was found in normal cybrids treated with aflibercept and while the AMD values trended lower, they were not significant. This data suggests that anti-VEGF drugs can cause loss of phagocytic function.

Automated retinal health diagnosis using pyramid histogram of visual words and Fisher vector techniques

Untreated age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma may lead to irreversible vision loss. Hence, it is essential to have regular eye screening to detect these eye diseases at an early stage and to offer treatment where appropriate. One of the simplest, non-invasive and cost-effective techniques to screen the eyes is by using fundus photo imaging. But, the manual evaluation of fundus images is tedious and challenging. Further, the diagnosis made by ophthalmologists may be subjective. Therefore, an objective and novel algorithm using the pyramid histogram of visual words (PHOW) and Fisher vectors is proposed for the classification of fundus images into their respective eye conditions (normal, AMD, DR, and glaucoma). The proposed algorithm extracts features which are represented as words. These features are built and encoded into a Fisher vector for classification using random forest classifier. This proposed algorithm is validated with both blindfold and ten-fold cross-validation techniques. An accuracy of 90.06% is achieved with the blindfold method, and highest accuracy of 96.79% is obtained with ten-fold cross-validation. The highest classification performance of our system shows the potential of deploying it in polyclinics to assist healthcare professionals in their initial diagnosis of the eye. Our developed system can reduce the workload of ophthalmologists significantly.

Rate of Macular Ganglion Cell-inner Plexiform Layer Thinning in Glaucomatous Eyes With Vascular Endothelial Growth Factor Inhibition.

To evaluate the rate of progressive macular ganglion cell-inner plexiform layer (GCIPL) thinning in patients with open-angle glaucoma (OAG) who had been treated with intravitreal antivascular endothelial growth factor (VEGF) injection for wet age-related macular degeneration (AMD). This study was a retrospective modified case control study with fellow eye comparison. We enrolled bilateral OAG patients who had been treated with repeated anti-VEGF injections for unilateral wet AMD and followed-up on for a minimum of 24 months by Cirrus high-definition optical coherence tomography. The rate of macular GCIPL thinning was determined by linear regression of serial optical coherence tomography GCIPL thickness measurements over time. We compared the rate of macular GCIPL thinning between anti-VEGF-treated eyes and fellow untreated dry AMD eyes. This study involved 32 OAG eyes of 16 subjects. The total follow-up period was 58.4±25.5 (24 to 98) months, and the mean number of anti-VEGF injections was 10.6±10.4 (3 to 40). The eyes with repeated anti-VEGF treatment differed significantly from their fellow eyes in the rate of GCIPL thinning (-2.95±3.58 vs. -0.77±0.95 µm/y, P=0.015). Also, multivariable regression analyses showed that anti-VEGF injection was significantly associated with the rate of GCIPL thinning (P=0.025). In subjects with bilateral OAG, the rate of GCIPL thinning is significantly faster in eyes treated with anti-VEGF injection for wet AMD than in untreated dry AMD fellow eyes. This finding suggests that in glaucomatous eyes, VEGF inhibition could play a role, at least in part, in progressive change of inner retinal layers.

Comparison of Ranibizumab and Bevacizumab for Neovascular Age-Related Macular Degeneration According to LUCAS Treat-and-Extend Protocol

To compare the efficacy and safety of bevacizumab versus ranibizumab when administered according to a treat-and-extend protocol for the treatment of neovascular age-related macular degeneration (AMD). Multicenter, randomized, noninferiority trial with a noninferiority limit of 5 letters. Patients aged ≥ 50 years with previously untreated neovascular AMD in 1 eye and best-corrected visual acuity (BCVA) between 20/25 and 20/320. Patients were randomly assigned to receive ranibizumab 0.5 mg or bevacizumab 1.25 mg intravitreal injections. Monthly injections were given until inactive disease was achieved. The patients were then followed with a gradual extension of treatment interval by 2 weeks at a time up to a maximum of 12 weeks. If signs of recurrent disease appeared, the treatment interval was shortened by 2 weeks at a time. Change in visual acuity at 1 year. Between March 2009 and July 2012, 441 patients were randomized at 10 ophthalmological centers in Norway. The 1-year visit was completed by 371 patients. In the per protocol analysis at 1 year, bevacizumab was equivalent to ranibizumab, with 7.9 and 8.2 mean letters gained, respectively (95% confidence interval [CI] of mean difference, -2.4 to 2.9; P = 0.845). The intention-to-treat analysis was concordant. There was no significant difference in measured central retinal thickness (CRT), with a mean decrease of -112 μm for bevacizumab and -120 μm for ranibizumab (95% CI of mean difference, -13 to 28; P = 0.460). There was a statistically significant difference (P = 0.001) between the drugs regarding the number of treatments: 8.9 for bevacizumab and 8.0 for ranibizumab. There were fewer arteriothrombotic events in the bevacizumab group (1.4%) than in the ranibizumab group (4.5%) (P = 0.050) and significantly more cardiac events in the ranibizumab group (P = 0.036). However, patients treated with ranibizumab more often had a history of myocardial infarction (P = 0.021). Bevacizumab and ranibizumab had equivalent effects on visual acuity at 1 year when administered according to a treat-and-extend protocol. The visual acuity results at 1 year were comparable to those of other clinical trials with monthly treatment. The numbers of serious adverse events were small.

Ocular surface temperature in age-related macular degeneration.

Background. The aim of this study is to investigate the ocular thermographic profiles in age-related macular degeneration (AMD) eyes and age-matched controls to detect possible hemodynamic abnormalities, which could be involved in the pathogenesis of the disease. Methods. 32 eyes with early AMD, 37 eyes with atrophic AMD, 30 eyes affected by untreated neovascular AMD, and 43 eyes with fibrotic AMD were included. The control group consisted of 44 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, diabetes mellitus, and a body temperature higher than 37.5°C. A total of 186 eyes without pupil dilation were investigated by infrared thermography (FLIR A320). The ocular surface temperature (OST) of three ocular points was calculated by means of an image processing technique from the infrared images. Two-sample t-test and one-way analysis of variance (ANOVA) test were used for statistical analyses. Results. ANOVA analyses showed no significant differences among AMD groups (P value >0.272). OST in AMD patients was significantly lower than in controls (P > 0.05). Conclusions. Considering the possible relationship between ocular blood flow and OST, these findings might support the central role of ischemia in the pathogenesis of AMD.

Long‐term results of the effect of intravitreal ranibizumab on the retinal arteriolar diameter in patients with neovascular age‐related macular degeneration

To study the effect of intravitreal (IVT) ranibizumab on the retinal arteriolar diameter in patients with neovascular age-related macular degeneration (AMD). Ten eyes of 10 patients with previously untreated neovascular AMD were included. All eyes had three monthly IVT injections of ranibizumab and then were retreated as needed, based on visual acuity and optical coherence tomography (OCT) criteria. The diameter of the retinal arterioles was measured in vivo with a retinal vessel analyser (RVA) before the first IVT injection, 7 and 30 days after the first, the second and the third injection, and at month 12 of follow-up. A significant vasoconstriction of the retinal arterioles was observed following each one of the first three IVT injections of ranibizumab. Thirty days following the first, second and third injection, there was a mean decrease of 8.4 ± 3.2%, 11.9 ± 4.5% and 18.5 ± 7.2%, respectively, of the retinal arteriolar diameter compared with baseline (p < 0.01). At month 12, the vasoconstriction was still present with a mean decrease of 19.1 ± 8.3% of the retinal arteriolar diameter compared with baseline (p < 0.01). Median number of ranibizumab injections was 4 (range 3-10). There was no correlation between the number of injections and percentage diameter decrease at month 12 (r = -0.54, p > 0.1). There was no significant change in mean arterial pressure (MAP) during the period of follow-up (p > 0.05). These results suggest that IVT ranibizumab induces sustained retinal arteriolar vasoconstriction in eyes with neovascular AMD.

New Biomarker for Neovascular Age-Related Macular Degeneration: Eotaxin-2

Recently, eotaxin-CCR3 was reported to play an important role in choroidal neovascularization (CNV) development and was documented to be superior than vascular endothelial growth factor-A treatment when tested in CNV animals. As eotaxin studies are lacking in the human age-related macular degeneration (AMD) patients, we sought to determine whether eotaxin-2 (CCL24) has any association with inflammatory processes that occur in CNV. CCL24 levels were determined by enzyme linked immunosorbant assay (ELISA) after normalization to total serum protein and levels of ELISA were correlated to various risk factors in about 133 AMD patients and 80 healthy controls. The CCL24 levels were significantly higher in wet AMD patients as compared with dry AMD and normal controls. There was a significant difference when compared among wet AMD patients (i.e., minimally classic, predominantly classic, and occult). We also report significant difference in the CCL24 levels of Avastin-treated and untreated AMD patients. This study shows that CCL24 levels were found to be significantly increased in AMD patients despite Avastin treatment as compared with normal controls and those without Avastin, indicating that CCL24 may have an association with CNV and may be an important target to validate future therapeutic approaches in AMD in tandem with Avastin treatment.

Oxygen metabolism in age related macular degeneration

AbstractPurpose To determine whether oxygen saturation in retinal vessels of patients with age‐related macular degeneration (AMD) is different from that of a healthy population.Methods The non‐invasive retinal oximeter is based on a fundus camera. It simultaneously captures images of the retina at 600 nm and 570 nm and estimates retinal vessel oxygen saturation. Mean oxygen saturation of hemoglobin was measured in retinal arterioles and venules of 28 individuals with AMD, 6 were males. Eight patients had early AMD in at least one eye, 8 patients had untreated exudative AMD in at least one eye, and 12 patients had early AMD in one eye and untreated exudative AMD in the other eye. The age of AMD patients was 78 ± 9 years (mean ± SD) compared to 66 ± 4 years for the healthy controls (n=26).Results Oxygen saturation of hemoglobin in arterioles, after adjusting for vessel width, was 94.3 ± 3.7% in the healthy population compared to 93.5 ± 3.1% in early AMD (n= ;p=0.42) and 93.7 ± 3.8% in exudative AMD (n= ;p=0.55). The corresponding values in venules were 60.9 ± 5.6% in healthy eyes compared to 64.9 ± 7.0% in exudative AMD (p=0.017). In eleven patients with early AMD in one eye and exudative AMD in the other eye, oxygen saturation in arterioles was 93.5 ± 3.0% and 92.4 ± 2.8% (p=0.52) and in venules 66.3 ± 4.9% and 64.4 ± 5.3% (p=0.080).Conclusion Oxygen saturation in venules in exudative AMD is higher than in healthy controls and there is a similar trend in early AMD. Arteriovenous difference is smaller in AMD subjects than normals. The study suggests that retinal oxygen metabolism is affected in AMD. Commercial interest

Aqueous Humor Levels of Vascular Endothelial Growth Factor Before and After Intravitreal Bevacizumab in Type 3 Versus Type 1 and 2 Neovascularization. A Prospective, Case-Control Study

To determine the aqueous levels of vascular endothelial growth factor (VEGF) in patients with type 3 neovascularization (NV) secondary to age-related macular degeneration (AMD) and to compare the levels of those with type 1 and 2 NV secondary to AMD before and after administration of intravitreal bevacizumab (IVB). Prospective, case-control study. Aqueous samples were collected from 29 eyes of 29 patients with untreated wet AMD at baseline (day of the first IVB), month 1 (day of the second IVB), and month 2 (day of the third IVB). Among them, 10 eyes presented with type 1, 9 with type 2, and 10 with type 3 NV. A group of 14 aqueous samples from 14 patients who underwent cataract surgery without other ocular or systemic disease comprised the controls. Main outcome measures were concentration of VEGF at baseline and after IVB in the 3 NV groups; secondary outcome measures included best-corrected visual acuity (BCVA) and central macular thickness (CMT) changes after IVB. Levels of VEGF were determined by commercially available enzyme-linked immunosorbent assay kits. VEGF concentrations in aqueous humor at baseline were higher in patients with type 3 NV when compared to controls (P = .0001) and type 1 and 2 NV patients (P = .002 and P = .0001 respectively). At month 1, levels of VEGF were significantly reduced compared to baseline (P < .05) and significantly lower compared to the controls (P < .005) in each NV group. These low levels were maintained at the 2-month interval. BCVA significantly improved in type 1 and 2 NV groups (P < .05). CMT significantly reduced in each NV group compared to baseline (P < .05). In eyes with untreated wet AMD, aqueous levels of VEGF are significantly higher in type 3 NV than in type 1 or 2 NV. Regardless of the type of NV, aqueous VEGF levels significantly reduce 1 month after IVB as compared to both the baseline measurements and the values recorded in age-matched controls. These decreases are maintained at 2 months after administering a second IVB 30 days after the initial injection.

RheoNet Registry Analysis of Rheopheresis for Microcirculatory Disorders With a Focus on Age‐Related Macular Degeneration

The purpose of establishing the RheoNet registry was to evaluate the safety and efficacy of rheopheresis, a specific method of therapeutic apheresis used to treat microcirculatory disorders. Apheresis centers providing rheopheresis therapy and physicians caring for the underlying disease were asked to participate in the registry, and the registry data were analyzed for safety and tolerability. Age-related macular degeneration (AMD) was selected as a model disease to evaluate efficacy. The RheoNet registry was successfully established recording 7722 rheopheresis treatments of 1110 patients, including 833 AMD patients. The mean age of patients was 72 years. Adverse events (AE) were reported in 5.67% of treatments, but termination of the treatment session was only required in 0.48%. Transient hypotension was the most frequently reported AE. No age-related increase in AE was observed. Ophthalmological data of 428 eyes (of 279 treated patients) with dry AMD could be analyzed; 85 eyes of 55 untreated AMD patients served as the control. At 6.75 +/- 5.25 months post-baseline, 42% of the treated eyes had improved visual acuity. The proportion of eyes with a decline in visual acuity was 17%, compared to 40% in the untreated controls (P < 0.01). The RheoNet registry has been successfully established and data analysis revealed that rheopheresis is a safe outpatient treatment for microcirculatory disorders. Moreover, RheoNet currently provides the largest evaluation of the efficacy of rheopheresis for dry AMD. Registry analysis contributes to a safe and appropriate use of rheopheresis in clinical practice.

Let us wake the nation on the treatment for age-related macular degeneration

To assess stakeholder perceptions of the quality of life associated with age-related macular degeneration (AMD). Ophthalmologists underestimate patient quality of life associated with AMD by 96-750%, more so at the better end of the visual spectrum. Other physicians and the general population have essentially no appreciation for the great quality-of-life loss associated with severe AMD. They equate it with the quality of life associated with entities such as carpal tunnel syndrome and ureteral calculi. Ophthalmologists should educate colleagues and the general population about the severe quality-of-life loss associated with untreated AMD. There is gross under appreciation of the ravages of the disease, whereas the same can be said for vascular endothelial growth factor A therapy, one of the greatest advances across all of medicine in the past decade.

Results of One-Year's Treatment with Ranibizumab for Exudative Age-related Macular Degeneration in a Clinical Setting

To evaluate the results of 1 year of treatment with intravitreal ranibizumab for exudative age-related macular degeneration (AMD) in a clinical setting. Nonrandomized, single-center, retrospective, interventional case series. Retrospective analysis of consecutive charts and angiograms of patients with previously untreated exudative AMD, treated in one or both eyes with ranibizumab between January 2 and October 31, 2007. The following were recorded for each patient: age at presentation, gender, treated eye, type of choroidal neovascularization, visual acuity (VA) measured on an Early Treatment Diabetic Retinopathy Study chart at baseline and at 52 +/- 6 weeks, the number of performed intravitreal (IVT) injections, and follow-up examinations. The 122 patients comprised 85 women (70%) and 37 men ranging in age from 56 to 91 years (mean +/- standard deviation, 78.3 +/- 7). In all, 124 eyes were treated on a pro re nata basis after 1 or 3 initial IVT injections. The mean number of IVT injections was 3.79 +/- 1.39 (range, 1 to 7). The mean number of follow-up visits was 8.07 +/- 1.44 (range, 4 to 12). Mean VA +/- standard deviation changed from 56.15 +/- 14 to 56.89 +/- 17 letters (VA gain, +0.7 letters). The results showed that VA stabilized rather than improved and compared unfavorably with the gains found in randomized clinical trials and the Prospective Optical Coherence Tomography Imaging of Patients with Neovascular AMD Treated with intraOcular Ranibizumab (PrONTO) Study. However in this study, patients were examined less frequently and were treated far less frequently. The present results suggest that a long, regular follow-up is necessary for patients treated with ranibizumab to obtain and preserve significant visual gain, and not only to achieve visual stabilization.

Focal Macular Electroretinograms in Eyes with Wet-type Age-Related Macular Degeneration

To study the properties of the focal macular electroretinograms (fmERGs) in eyes with untreated wet-type age-related macular degeneration (AMD). fmERGs were recorded from 157 eyes of 157 consecutive patients with untreated wet-type AMD (113 men, 44 women; age, 71.3 +/- 8.0 years). The fmERGs were recorded under direct fundus observation using a modified infrared fundus camera and a 15 degrees stimulus spot. Amplitudes and implicit times of the fmERGs recorded from the AMD patients were compared with those from 21 age-similar healthy controls. The amplitudes of fmERGs in the AMD patients were significantly smaller (P < 0.001) and the implicit times were significantly longer (P < 0.001) than the corresponding values in the control eyes. There was a significant correlation between amplitude and implicit time of the fmERG and visual acuity (logMAR), but the degree of correlation was weak. The difference in the b/a amplitude ratio between the AMD patients and healthy controls was not significant. The significant reduction in amplitude and the severe delay in implicit times of a- and b-waves of the fmERGs indicated significant functional alterations in the inner and the outer retinal layers of the macular area of eyes with wet-type AMD.

The Natural History and Prognosis of Neovascular Age-Related Macular Degeneration: A Systematic Review of the Literature and Meta-analysis

To describe the natural history and progression of visual loss in eyes with untreated neovascular age-related macular degeneration (AMD). Systematic review and meta-analysis. Four thousand three hundred sixty-two untreated neovascular AMD patients from published interventional studies. A systematic review of the literature from 1980 to August 2005 was performed. Studies reporting disease progression outcomes for untreated patients with neovascular AMD were included. Outcome measures were summarized using simple counts and means. Random effects meta-analyses were conducted and tests of heterogeneity were performed where appropriate. Changes in visual acuity (VA) loss, development of comorbidities, and fellow eye involvement. Fifty-three primary studies were included. Nearly half of the studies (28) were randomized clinical trials. The quality of the studies was high, with over 80% providing level I or II evidence. Mean baseline VA among study patients was 0.64 logarithm of the minimum angle of resolution (logMAR) (approximately 20/87 Snellen). The mean VA change in logMAR progressed from 0.1 (1 line lost) at 3 months to 0.3 (2.7 lines lost) after 12 months and 0.4 (4 lines lost) after 24 months. The proportion of patients who developed severe vision loss (>6 lines) from baseline increased from 21.3% at 6 months to 41.9% by 3 years. The proportion of patients with VA worse than logMAR 1.0 (20/200 Snellen) increased from 19.7% at baseline to 75.7% by 3 years. Neovascular AMD developed in the fellow eye in 12.2% of patients by 12 months and in 26.8% by 4 years. Meta-analyses of vision outcome by subtype of neovascular AMD were not possible. A doubling of the visual angle of presenting VA may be expected to occur in the year after initial presentation in eyes with untreated neovascular AMD. No conclusions can be drawn as to the differences in rates of disease progression by neovascular AMD subtype. The diversity of reporting formats, paucity of long-term natural history data, and heterogeneity among the reported clinical studies impose limits to the clear understanding of long-term prognosis for visual function in neovascular AMD.

Influence of photodynamic therapy for age related macular degeneration upon subjective vision related quality of life

Photodynamic therapy (PDT) has been used in the treatment of choroidal neovascularisation secondary to age-related macular degeneration (AMD). This study prospectively investigated patients' subjective change in visual function following PDT as treatment for AMD. Eighty-two consecutive patients receiving PDT in Tasmania, Australia, between May and November 2003 were recruited. In conjunction with a comprehensive clinical examination, the Visual Function-14 (VF-14) questionnaire was administered. Final follow-up occurred between February and March 2005. The VF-14 was scored by traditional summary scoring and by Rasch analysis. Five of the 82 (6.1%) subjects recruited were excluded from analysis. PDT was performed on average 5.7+/-2.6 times per patient. Raw VF-14 scores tended towards being significantly lower at follow-up than at baseline (67.6+/-27.2 against 64.5+/-27.7; P=0.052), and did significantly deteriorate using a collapsed Rasch analysis (P=0.0102). Following treatment, 38 (47.5%) eyes had lost three or more Snellen lines of best-corrected visual acuity. Patients undergoing PDT typically report reasonable visual function. In parallel with visual acuity, self-reported visual function may deteriorate slightly after PDT for AMD, but not as much as reported in untreated AMD.