The significance of early detection of age-related macular degeneration: Richard & Hinda Rosenthal Foundation lecture, The Macula Society 29th annual meeting

BACKGROUND: The main cause for visual loss in age-related macular degeneration (AMD) is the development of choroidal neovascularization (CNV), which has been shown to occur in 18% of patients over 5 years. Even though satisfactory treatments for CNV are available, in the majority of cases no improvement in visual acuity occurs and in those it does it is mostly limited. Early detection has the potential of significantly improving the final visual outcome of patients who develop subfoveal CNV. METHODS: This review is a summary of the importance of early detection in the management of AMD, in view of the current available treatment methods. It is a review of the results of early detection of AMD using the Preferential Hyperacuity Perimeter (PHP). RESULTS: Awareness for symptoms, use of the Amsler grid and monitoring by an ophthalmologist are not satisfactory means for early detection of AMD. The PHP has good sensitivity and specificity in detecting CNV patient early and differentiate them from intermediate AMD. CONCLUSION: In an era of excellent treatments available for CNV treatment, early detection of CNV by novel technology modalities such as the PHP at a frequency that allows early detection (approximately 4 times a year) is crucial in the armamentarium of AMD patient management.     

萎缩型年龄相关性黄斑变性形态学及功能学检查技术进展

年龄相关性黄斑变性(age-related macular degeneration,AMD)是50岁以上人群主要的致盲性眼病,其中萎缩型占AMD患病总数的85％ ～ 90％.随着光谱成像、眼底自发荧光、光学相干断层扫描、微视野、多焦视网膜电流图及其他新方法在眼科临床的应用,人们对萎缩型AMD病变的形态及功能改变有了更深入和全面的认识,本文就近年来的相关进展予以综述.     

Changes in fluorescein angiogram early after surgical removal of choroidal neovascularization in age-related macular degeneration

BACKGROUND: Retinal pigment epithelial (RPE) defects inevitably occur in surgical removal of choroidal neovascularization (CNV) in age-related macular degeneration (AMD). RPE can proliferate and cover the denuded area, but the healing process has not been investigated in humans. To understand the RPE wound-healing process, we estimated the changes in fluorescein angiograms early after CNV removal. METHODS: Ten consecutive patients with exudative AMD underwent CNV removal without gas tamponade. Fluorescein angiography was performed within 4 days of surgery and again 1 or 2 weeks postoperatively. Areas of leakage were measured using a computer-assisted image analyser. The decreasing rate of leakage was calculated as the change in disc areas of leakage per day (DA/day). RESULTS: The rates of decreasing leakage ranged from 0 to 0.42 DA/day (mean, 0.24 +/- 0.15 DA/day; median, 0.26 DA/day). The rate of decreasing leakage correlated with changes in visual acuity (r = 0.642, P = 0.0456). CONCLUSION: The retinal pigment epithelial wound after surgical removal of choroidal neovascularization may heal at the rate of 0.24 disc areas/day based on the blood retinal barrier function in patients with age-related macular degeneration. A faster rate of decreasing leakage may be associated with better visual prognosis.     

Complement in age-related macular degeneration: a focus on function

Age-related macular degeneration (AMD) is an inflammatory disease, which causes visual impairment and blindness in older people. The proteins of the complement system are central to the development of this disease. Local and systemic inflammation in AMD are mediated by the deregulated action of the alternative pathway of the complement system. Variants in complement system genes alter an individual's risk of developing AMD. Recent studies have shown how some risk-associated genetic variants alter the function of the complement system. In this review, we describe the evolution of the complement system and bring together recent research to form a picture of how changes in complement system genes and proteins affect the function of the complement cascade, and how this affects the development of AMD. We discuss the application of this knowledge to prevention and possible future treatments of AMD.     

Decoding simulated neurodynamics predicts the perceptual consequences of age-related macular degeneration

Age-related macular degeneration (AMD) is the major cause of blindness in the developed world. Though substantial work has been done to characterize the disease, it is difficult to predict how the state of an individual's retina will ultimately affect their high-level perceptual function. In this paper, we describe an approach that couples retinal imaging with computational neural modeling of early visual processing to generate quantitative predictions of an individual's visual perception. Using a patient population with mild to moderate AMD, we show that we are able to accurately predict subject-specific psychometric performance by decoding simulated neurodynamics that are a function of scotomas derived from an individual's fundus image. On the population level, we find that our approach maps the disease on the retina to a representation that is a substantially better predictor of high-level perceptual performance than traditional clinical metrics such as drusen density and coverage. In summary, our work identifies possible new metrics for evaluating the efficacy of treatments for AMD at the level of the expected changes in high-level visual perception and, in general, typifies how computational neural models can be used as a framework to characterize the perceptual consequences of early visual pathologies.     

On phagocytes and macular degeneration

Age related macular degeneration (AMD) is a complex multifactorial disease caused by the interplay of age and genetic and environmental risk factors. A common feature observed in early and both forms of late AMD is the breakdown of the physiologically immunosuppressive subretinal environment and the protracted accumulation of mononuclear phagocytes (MP). We here discuss the origin and nature of subretinal MPs, the mechanisms that lead to their accumulation, the inflammatory mediators they produce as well as the consequences of their chronic presence on photoreceptors, retinal pigment epithelium and choroid. Recent advances highlight how both genetic and environmental risk factors directly promote subretinal inflammation and tip the balance from a beneficial inflammation that helps control debris accumulation to detrimental chronic inflammation and destructive late AMD. Finally, we discuss how changes in life style or pharmacological intervention can help to break the vicious cycle of inflammation and degeneration, restore the immunosuppressive properties of the subretinal space, and reestablish homeostasis.     

Proteomics of the retinal pigment epithelium reveals altered protein expression at progressive stages of age-related macular degeneration

PURPOSE: Age-related macular degeneration (AMD) is characterized clinically by changes in the retinal pigment epithelium (RPE), formation of drusen between the RPE and the underlying vasculature, geographic atrophy, and choroidal neovascularization. Later clinical stages are accompanied by impaired central vision. A limited understanding of the molecular events responsible for AMD has constrained the development of effective treatments. A proteomics approach was used to investigate the underlying mechanisms of AMD and to identify proteins exhibiting significant changes in expression with disease onset and progression. METHODS: Human donor eyes were categorized into one of four progressive stages of AMD. Proteins from the RPE were resolved and quantified by two-dimensional (2-D) gel electrophoresis. Proteins exhibiting significant expression changes at different disease stages were identified by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. 2-D and semiquantitative one dimensional (1-D) Western blot analyses were used to determine whether changes identified by the proteomic analysis were specific for a protein subpopulation or representative of the entire protein population. RESULTS: Proteins were identified from several critical pathways that changed at early and late disease stages, indicating potential causal mechanisms and secondary consequences of AMD, respectively. Proteins involved in protecting from stress-induced protein unfolding and aggregation, mitochondrial trafficking and refolding, and regulating apoptosis changed early in the disease process. Late-stage changes occurred in proteins that regulate retinoic acid and regeneration of the rhodopsin chromophore. CONCLUSIONS: These results provide the first direct evidence of AMD stage-specific changes in human RPE protein expression and provide a basis for functional investigation of AMD that may ultimately suggest new therapeutic strategies.     

Progression of age-related geographic atrophy: role of the fellow eye

PURPOSE. To evaluate the role of fellow eye status in determining progression of geographic atrophy (GA) in patients with age-related macular degeneration (AMD). METHODS. A total of 300 eyes with GA of 193 patients from the prospective, longitudinal, natural history FAM Study were classified into three groups according to the AMD manifestation in the fellow eye at baseline examination: (1) bilateral GA, (2) early/intermediate AMD, and (3) exudative AMD. GA areas were quantified based on fundus autofluorescence images using a semiautomated image-processing method, and progression rates (PR) were estimated using two-level, linear, mixed-effects models. RESULTS. Crude GA-PR in the bilateral GA group (mean, 1.64 mm(2)/y; 95% CI, 1.478-1.803) was significantly higher than in the fellow eye early/intermediate group (0.74 mm(2)/y, 0.146-1.342). Although there was a significant difference in baseline GA size (P = 0.0013, t-test), and there was a significant increase in GA-PR by 0.11 mm(2)/y (0.05-0.17) per 1 disc area (DA; 2.54 mm(2)), an additional mean change of -0.79 (-1.43 to -0.15) was given to the PR beside the effect of baseline GA size. However, this difference was only significant when GA size was ≥1 DA at baseline with a GA-PR of 1.70 mm(2)/y (1.54-1.85) in the bilateral and 0.95 mm(2)/y (0.37-1.54) in the early/intermediate group. There was no significant difference in PR compared with that in the fellow eye exudative group. CONCLUSIONS. The results indicate that the AMD manifestation of the fellow eye at baseline serves as an indicator for disease progression in eyes with GA ≥ 1 DA. Predictive characteristics not only contribute to the understanding of pathophysiological mechanisms, but also are useful for the design of future interventional trials in GA patients.     

Multifocal pupillography identifies retinal dysfunction in early age-related macular degeneration

Background

Early age-related macular degeneration (AMD) is common among the elderly. While only a small number progress to sight-threatening stages of AMD, identifying prognostic functional markers remains paramount. Here, we objectively evaluate retinal function in patients with large drusen by multifocal pupillographic objective perimetry (mfPOP). Different temporal presentation rates and luminances were compared to optimize parameters for high signal to noise ratios (SNR) and diagnosticity for early AMD.

Methods

Pupil responses were recorded from 19 early AMD patients (30 eyes) and 29 age-matched control subjects. We compared a luminance-balanced stimulus ensemble and two unbalanced stimulus variants, each consisting of 44 independent stimulus regions per eye extending from fixation to 15? eccentricity. Video cameras recorded pupil responses for each eye under infrared illumination. The amplitudes and delays of the peak responses were analysed by multivariate linear models. The diagnostic accuracy of the stimulus variants was compared using areas under the curve (AUC) of receiver operator characteristic (ROC) plots.

Results

Early AMD eyes differed significantly from normal in their mean constriction amplitudes (?2.22?±?0.15 dB, t?=??14.8) and delays (17.92?±?1.2 ms, t?=?14.9). The brightest stimulus ensembles produced the highest median SNRs of 3.45 z-score units; however, the balanced method was found to be the most diagnostic. AUC values of 0.95?±?0.03 (mean ± SE) for early AMD were obtained when the asymmetry of response amplitudes between eyes was considered.

Conclusions

The mfPOP responses of early AMD eyes showed significant abnormality in response amplitudes and peak time. The ROC AUCs of 95 % suggest that mfPOP is a sensitive tool for detecting early abnormalities in AMD and longitudinal studies measuring progression of retinal dysfunction are warranted.     

The proteome of central and peripheral retina with progression of age-related macular degeneration

PURPOSE: A growing understanding of the molecular events in age-related macular degeneration (AMD) has lead to targeted therapies for a select group of patients with advanced AMD. Development of therapies for the earlier stages requires further elucidation of disease mechanisms. In this study, a proteomics approach was used to identify proteins that had altered content in human donor eyes with progression of AMD. METHODS: The early molecular events associated with AMD were identified by comparing the proteome of the macular and peripheral neurosensory retina during four progressive stages of AMD. Proteins were resolved and quantified by two-dimensional gel electrophoresis. Twenty-six proteins exhibited changes in content and were identified by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. Two-dimensional (2-D) and semiquantitative one-dimensional (1-D) Western blot analyses were used to determine whether changes identified by proteomic analysis were specific for a protein subpopulation or representative of the entire protein population. RESULTS: Twenty-six proteins were identified that exhibited changes at disease onset or with progression (indicating potential causal mechanisms) and at end-stage disease (indicating potential secondary consequences). These proteins are involved in key functional pathways, such as microtubule regulation and protection from stress-induced protein unfolding. Approximately 60% of the proteins exhibited changes specific to either the macula or periphery, with the remaining 40% changing in both regions. These results imply that both the macula and periphery are affected by AMD. CONCLUSIONS: This study provides the first direct evidence of AMD stage- and region-specific changes in retinal protein levels and highlights potential novel, disease-related proteins and biochemical pathways for future studies of AMD.     

Intravitreales Bevacizumab bei der neovaskulären altersabhängigen Makuladegeneration

The efficacy and safety of the therapeutic anti-VEGF concept has already been demonstrated for pegaptanib and ranibizumab. Bevacizumab acts as an antibody against all VEGF-A isoforms and has been developed for oncological indications with intravenous application. Initial reports on intravitreal administration in patients with neovascular age-related macular disease (AMD) have shown beneficial morphological and functional effects. In the meantime, bevacizumab has been used off-label in thousands of patients with AMD. However, data from prospective, controlled, randomized trials on both safety and efficacy are lacking. Herein recent experiences with bevacizumab are summarized and discussed. Furthermore, a web-based platform for online data registration and pooled analyses is presented.     

Implications of genetic variation in the complement system in age-related macular degeneration

Age-related macular degeneration (AMD) is the main cause of vision loss among the elderly in the Western world. While AMD is a multifactorial disease, the complement system was identified as one of the main pathways contributing to disease risk. The strong link between the complement system and AMD was demonstrated by genetic associations, and by elevated complement activation in local eye tissue and in the systemic circulation of AMD patients. Several complement inhibitors have been and are being explored in clinical trials, but thus far with limited success, leaving the majority of AMD patients without treatment options to date. This indicates that there is still a gap of knowledge regarding the functional implications of the complement system in AMD pathogenesis and how to bring these towards clinical translation. Many different experimental set-ups and disease models have been used to study complement activation in vivo and in vitro, and recently emerging patient-derived induced pluripotent stem cells and genome-editing techniques open new opportunities to study AMD disease mechanisms and test new therapeutic strategies in the future. In this review we provide an extensive overview of methods employed to understand the molecular processes of complement activation in AMD pathogenesis. We discuss the findings, advantages and challenges of each approach and conclude with an outlook on how recent, exciting developments can fill in current knowledge gaps and can aid in the development of effective complement-targeting therapeutic strategies in AMD.     

Anecortave acetate for treating or preventing choroidal neovascularization

Although there have been treatments and pharmacologic agents approved in the last several years to treat advanced stages of AMD, these treatments do not halt disease progression. Furthermore, it is clear that when dry AMD progresses to CNV in one eye, there is a substantial risk that it will progress in the other eye. Sight-preservation at early stages of the disease should be a key goal of research, yet there are no approved therapies for halting the progression of early stages of AMD. Patients may be encouraged to use vitamin supplements, cease smoking, and eat a healthy diet; however, these recommendations are not appropriate for all patients, nor are they embraced by everyone. A pharmacologic agent capable of targeting the early stages of AMD would be a welcome addition to the armamentarium of options for managing AMD. Trials are ongoing to evaluate the role of anecortave acetate as a prophylactic treatment to slow the progression of the early stages of AMD. Completed clinical studies have demonstrated that anecortave acetate possesses a mechanism of action that decreases CNV growth irrespective of the inciting angiogenic stimulus, has a dosing-interval that allows its use as prophylactic therapy, and is safe. The economic benefits associated with prevention and progression to advanced AMD, in even a small proportion of cases, is significant and could result in substantial cost savings to society as a whole while providing countless benefits to individual patients in terms of continued independent function, self-sufficiency, and improved quality of life.     

New examination methods for macular disorders--application of diagnosis and treatment

To establish a diagnosis or evaluate the efficacy of treatment for macular disorders, we need methods to evaluate the anatomical and functional changes of these disorders. In this article, we describe several studies that we have conducted for 2 years. In section 1, we report our new methods for making a diagnosis and evaluating visual function in macular disorders. In section 2, we describe our trials of these examination methods in treatment. Here is the summary of our results. In section 1, to examine the structures of the macular area, we used a retinal thickness analyzer (RTA), a confocal scanning laser ophthalmoscope (Heidelberg Retina Tomograph, HRT), and optical coherence tomography (OCT) to measure retinal thickness and assess retinal microstructures. We compared retinal imaging analysis of various macular diseases obtained with these three instruments. With the RTA, we obtained good three-dimensional macular images displayed on a retinal thickness map, but the retinal thickness map did not demonstrate the thickened retina with dense retinal hemorrhages, and high backscattering from hard exudates might obscure the vitreoretinal interface. The HRT three-dimensional topographic image clearly showed the undulation of the retinal surface. However, it took a relatively long time to obtain the HRT image, and we sometimes could not obtain good topographic images because of fixation movement. Examination with the OCT allows confirmation of the retinal cross-sectional structures, such as retinoschisis or cystoid spaces and the vitreomacular interface, such as vitreous traction, that cannot be detected using other conventional methods with high resolution, but high reflectivity from dense hemorrhages obscured the deeper layers of the retinal structures. Measurement of retinal thickness obtained with both the RTA and OCT is highly reproducible, and there was significant correlation between the retinal thicknesses measured with the two instruments. We believe that these three instruments might contribute significantly to early, accurate diagnosis and better monitoring of the therapeutic effects of vitrectomy for macular diseases. In the future, if these fundus imaging analysis instruments can achieve higher resolution and can analyze three-dimensional retinal images, they will provide better information to clinically evaluate macular diseases. We demonstrated vitreous examination and examination from the retinal surface to the deeper retinal layer at the macular area using a scanning laser ophthalmoscope (SLO). The SLO examination with an argon laser and a large confocal aperture was useful for conducting kinetic examination of the vitreous opacity above the macula. With a diode laser and a ring aperture (dark-field mode), it was possible to examine the retina from the deeper retinal layer to the choroids. On the other hand, the SLO also allows us to conduct a functional examination of fixation. We demonstrated that the referred retinal locus of fixation may change during the follow-up period in patients whose central fixation is impaired due to macular disease, and we showed that the fixation behavior was related to the visual acuity. Therefore, the SLO is an ideal instrument for determining the visual field and the visual acuity before and after treatment in patients with macular disease, because of its precise localization of the examination point by directly observing the fundus and by monitoring fixation behavior. Our new program installed in the SLO allows us to complete the quantitative retinal sensitivity evaluation within 2 minutes, which is difficult to do using a conventional SLO program. Furthermore, we demonstrated for the first time that minute functional changes in the retina can be detected by the SLO under low background illuminance. Such changes cannot be detected under conventional conditions. In addition, the extrafoveal visual acuity of normal subjects and patients with macular disease was studied using this new SLO program. The iso-acuity lines could be illustrated by summarizing these results in normal subjects. The SLO acuity of the horizontal meridian is significantly better than that of the vertical meridian, and even in the nasal area adjacent to the optic disc, an acuity of better than 0.1 could be achieved. To evaluate macular function, we also investigated the blood flow of the choroid (CF), the retina (RF), and the choriocapillaris at the fovea (CCF). We investigated the CF in patients with age-related macular degeneration (AMD) using pulsatile ocular blood flow (POBF) measurements. In patients with exudative AMD, the POBF was significantly lower than in patients with nonexudative AMD or in control subjects. Decreased CF may play a role in the development of choroidal neovascularization in AMD. RF was measured using laser Doppler velocimetry (LDV). (ABSTRACT TRUNCATED)     

Radiation therapy in exudative age-related macular degeneration

It has been suggested that ionizing radiation at doses relatively safe to the optic nerve and retina exert an inhibitory and occlusive effect on the endothelial proliferation of choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD). The encouraging results of early studies in preservation or improvement of visual acuity and regression of the CNV gave rise to many clinical trials in different centers. Disparate radiation doses, dose fractions, type and rate of radiation administration have been used to determine the efficacy of radiotherapy in AMD. Conflicting treatment responses have been reported by different centers. Some studies provided evidence of beneficial treatment outcome in AMD, and others could not show any efficacy of ionizing radiation in the visual and morphological evolution of the disease. Data from the literature and our experience indicate that radiotherapy can be effective in regressing the leakage of the CNV in AMD. However, despite treatment visual deterioration continues and new CNV lesions develop. The observation of morphological progression in the disease process might be related to an unfavorable effect of radiation on the pathogenesis of AMD.     

Transplantation von Irispigmentepithel

Transplantation of iris pigment epithelial (IPE) cells to the subretinal space has been attempted as a therapeutic modality for the treatment of age-related macular degeneration (AMD). IPE cells are used because autologous cells are readily available and because IPE and RPE cells share a common embryonic origin, possess the capacity of transdifferentiation into other ocular cells, and share common morphological and functional characteristics. Once the technique of IPE cell transplantation was established in an animal mode, several clinical studies analyzed the behavior of IPE cell suspensions transplanted to the subretinal space of patients with AMD following surgical membrane extraction. In our experience, as well as that of other investigators, transplantation of IPE cells to the subretinal space of AMD patients prevents the recurrence of the subretinal neovascularization and stabilizes but does not improve visual acuity. Since IPE cells transplanted as a cell suspension do not appear to form a cell monolayer in the subretinal space, the transplantation of preformed IPE or RPE cell monolayers is being investigated as the development of an functional cell monolayer is mandatory if functional success, i.e., recovery of vision in AMD patients, is the ultimate goal of IPE cell transplantation.     

Relationship between Clinical Macular Changes and Retinal Function in Age-Related Macular Degeneration

Purpose. The aim of this study was to investigate the relationship between clinical macular changes and retinal function in age-related macular degeneration (AMD). Methods. We recruited 357 participants with visual acuity of better than 20/60 in the study eye, including 64 individuals with normal fundi and 293 AMD participants classified into 12 subgroups based upon the International Classification and Grading System. Visual function in the study eye was assessed using two steady-state tests (achromatic 14 Hz flicker [F14Hz] and isoluminant blue color [BCT]) and two adaptation measurements (cone photo-stress recovery rate [CRR] and rod dark adaptation recovery rate [RRR]). The groups were compared on their average psychophysical measurements and ranked according to functional deficiency. Results. Both adaptation parameters were significantly abnormal when only hard and/or intermediate drusen were evident (compared to controls, P < 0.023) and yielded considerably worse outcomes in cases with more advanced fundus changes (P < 0.001), but provided limited ability to discriminate between these cases (linear trend, CRR t = 0.68, P = 0.50 and RRR t = 1.76, P = 0.08). Steady-state measurements, however, declined gradually along the entire hierarchy of fundus changes (linear trend, F14Hz t = 10.16, P < 0.001 and BCT t = 11.19, P < 0.001) with F14Hz being able to detect significant functional change as early as in the intermediate drusen group, when compared to controls (P = 0.003). Conclusions. Steady state thresholds (F14Hz and BCT) and clinical signs showed significant concordance across the spectrum of early AMD fundus changes. This suggests that these tests may be an effective tool for monitoring progression of AMD to supplement clinical grading.     

Microperimetry and fundus autofluorescence in patients with early age-related macular degeneration

BACKGROUND: Early age-related macular degeneration (AMD) has been correlated with different functional alterations, but the exact relationship between fundus lesions and overlying sensitivity is not well known. The aim of this study was to compare fundus-related sensitivity (microperimetry) and fundus autofluorescence (FAF) of the macular area with drusen and pigment abnormalities in early AMD. METHODS: 13 consecutive patients with early AMD and visual acuity of 20/20 were studied by means of microperimetry, which automatically analyses macular light differential threshold and fixation patterns. Fundus colour photo and FAF of the macular area were recorded on the same day. Microperimetry was exactly (topographically) superimposed over FAF images. RESULTS: Macular sensitivity significantly decreased over large drusen (11.2 +/- 5.6 dB, p<0.0001) and over pigment abnormalities (13.1 +/- 3.6 dB, p<0.0001). When both characteristics were present the reduction was greater if compared with its absence (9.6 +/- 4.3 versus 15.0 +/- 4.5 dB, p<0.0001). Sensitivitity reduction was significant in areas with altered FAF when compared with areas with normal FAF (p<0.0001). CONCLUSIONS: Increased FAF in early AMD has a functional correlate exactly quantified by microperimetry. In retinal areas affected by early AMD retinal sensitivity deteriorates, despite good visual acuity. Microperimetry may allow the early detection of functional impairment caused by these lesions. Both microperimetry and FAF may be useful to monitor AMD progression.     

Age-related macular degeneration and quality of life: how to interpret a research paper in health-related quality of life

PURPOSE OF REVIEW: To review how to critically appraise a research article pertaining to changes in health-related quality of life (HRQoL) related to interventions for age-related macular degeneration (AMD). RECENT FINDINGS: We searched PubMed using a strategy that combined the text-words, "macular degeneration" and "quality of life" (n = 73; January 17, 2004), while limiting the search to "clinical trials" (n = 6; of which 3 were published within the past year). A randomized clinical trial evaluating the efficacy of self-management as an intervention for AMD has been selected to introduce the reader to the concept of how to critically review a research paper pertaining to HRQoL in AMD. Other pertinent articles used in this review include recent results published from the Age-Related Eye Disease Study and the Submacular Surgery Trial. SUMMARY: The NEI-VFQ is a reliable, valid, and responsive tool when applied to patients with AMD. Self-management of patients with AMD has been demonstrated to improve their HRQoL by way of an internally valid randomized clinical trial. In this issue of Current Opinion in Ophthalmology, we confront the issue of how to assess the validity and importance of a research paper pertaining to the issue of quality of life. To introduce this topic, we will present a real world clinical example to better understand how quality of life may aid in medical decision making.