A Screening Tool for Self-Evaluation of Risk for Age-Related Macular Degeneration: Validation in a Spanish Population.

Purpose: The objectives of this study were the creation and validation of a screening tool for age-related macular degeneration (AMD) for routine assessment by primary care physicians, ophthalmologists, other healthcare professionals, and the general population. Methods: A simple, self-administered questionnaire (Simplified Théa AMD Risk-Assessment Scale [STARS] version 4.0) which included well-established risk factors for AMD, such as family history, smoking, and dietary factors, was administered to patients during ophthalmology visits. A fundus examination was performed to determine presence of large soft drusen, pigmentary abnormalities, or late AMD. Based on data from the questionnaire and the clinical examination, predictive models were developed to estimate probability of the Age-Related Eye Disease Study (AREDS) score (categorized as low risk/high risk). The models were evaluated by area under the receiving operating characteristic curve analysis. Results: A total of 3854 subjects completed the questionnaire and underwent a fundus examination. Early/intermediate and late AMD were detected in 15.9% and 23.8% of the patients, respectively. A predictive model was developed with training, validation, and test datasets. The model in the test set had an area under the curve of 0.745 (95% confidence interval [CI] = 0.705-0.784), a positive predictive value of 0.500 (95% CI = 0.449-0.557), and a negative predictive value of 0.810 (95% CI = 0.770-0.844). Conclusions: The STARS questionnaire version 4.0 and the model identify patients at high risk of developing late AMD. Translational Relevance: The screening instrument described could be useful to evaluate the risk of late AMD in patients >55 years without having an eye examination, which could lead to more timely referrals and encourage lifestyle changes.

Exploring Consensus on Preventive Measures and Identification of Patients at Risk of Age-Related Macular Degeneration Using the Delphi Process.

BACKGROUND: Early identification of AMD can lead to prompt and more effective treatment, better outcomes, and better final visual acuity; several risk scores have been devised to determine the individual level of risk for developing AMD. Herein, the Delphi method was used to provide recommendations for daily practice regarding preventive measures and follow-up required for subjects at low, moderate, and high risk of AMD evaluated with the Simplified Test AMD Risk-assessment Scale (STARS®) questionnaire. METHODS: A steering committee of three experts drafted and refined 25 statements on the approach to be recommended in different clinical situations [general recommendations (n = 2), use of evaluation tools (n = 4), general lifestyle advice (n = 3), and AREDS-based nutritional supplementation (n = 5)] with the help of a group of international experts, all co-authors of this paper. Thirty retinal specialists from Europe and the US were chosen based on relevant publications, clinical expertise, and experience in AMD, who then provided their level of agreement with the statements. Statements for which consensus was not reached were modified and voted upon again. RESULTS: In the first round of voting, consensus was reached for 24 statements. After modification, consensus was then reached for the remaining statement. CONCLUSION: An interprofessional guideline to support preventive measures in patients at risk of AMD based on STARS® scoring has been developed to aid clinicians in daily practice, which will help to optimize preventive care of patients at risk of AMD.

Ranibizumab treatment patterns in prior ranibizumab-treated neovascular age-related macular degeneration patients: Real-world outcomes from the LUMINOUS study.

PURPOSE: To evaluate the effectiveness, safety, and treatment patterns of ranibizumab 0.5 mg in prior ranibizumab-treated patients with neovascular age-related macular degeneration (nAMD) enrolled in the LUMINOUS™ study. PATIENTS AND METHODS: LUMINOUS, a 5-year, prospective, multicenter, observational study, recruited 30,138 adult patients (treatment-naïve or prior ranibizumab-treated or other ocular treatments) across all approved indications for ranibizumab. Patients were treated as per local ranibizumab label of participating countries. Here we report the mean change in visual acuity (VA) at Year 1, treatment exposure, overall incidence of ocular, non-ocular adverse events (AEs) and serious AEs (SAEs) in prior ranibizumab-treated nAMD patients (n = 16,167). RESULTS: At baseline, the mean (standard deviation [SD]) age of patients was 78.4 (9.0) years, 59.0% were female, and 80.0% were Caucasian. At Year 1 (n = 10,168), the mean (SD) VA change was -1.6 (12.6) letters (baseline VA: 58.3 [19.0] letters) with a mean (SD) of 4.7 (3.1) ranibizumab injections. Stratified by duration of prior ranibizumab treatment of <1 (n = 4,112), 1 to <2 (n = 2,095), 2 to <3 (n = 1,506), 3 to <4 (n = 1,123), 4 to <5 (n = 689), and ≥5 (n = 256) years, the mean (SD) VA change at Year 1 were -1.2 (13.5), -2.0 (12.3), -2.0 (11.3), -1.9 (11.8), -2.5 (10.9), and 0.0 (11.2) letters, respectively. Mean (SD) VA change in patients who received ≤6 and >6 injections over 1 year was -1.8 (13.8) and +0.5 (12.5) letters, respectively. The rate of ocular/non-ocular AEs and SAEs across all prior ranibizumab-treated patients over 5 years were 13.29%/23.02% and 0.84%/13.66%, respectively. CONCLUSIONS: Overall, regardless of the prior ranibizumab-treatment duration, VA was maintained in these patients at Year 1, and those receiving ≥6 injections showed a trend towards gaining letters. There were no new safety signals. These results may help inform routine clinical practice to appropriately treat nAMD patients with ranibizumab to achieve optimal visual outcomes.

Retinal Pigment Epithelial and Outer Retinal Atrophy in Age-Related Macular Degeneration: Correlation with Macular Function.

The purpose of this study was to investigate the relationship between the retinal pigment epithelium (RPE) and outer retina changes, expressed in terms of sub-RPE illumination (SRI) on optical-coherence tomography (OCT), and central retinal function, measured by visual acuity and focal electroretinogram (fERG), in patients with non-exudative age-related macular degeneration (neAMD). In this retrospective study, 29 eyes of 29 patients affected by early (24.14%), intermediate (41.38%), and advanced (34.48%) neAMD were evaluated. All enrolled eyes were studied with OCT to measure the total area of SRI, by using an automated standardized algorithm. Visual acuity and fERG were assessed. The area of SRI was negatively correlated with fERG amplitude (r ≤ -0.4, p ≤ 0.02) and best-corrected visual acuity (BCVA) (r ≤ 0.4, p ≤ 0.04). Our results indicate that the severity of retinal pigment epithelium and outer retina atrophy (RORA), indirectly quantified through the detection of SRI areas by commercial OCT algorithms, is correlated with central retinal dysfunction, as determined by visual acuity and fERG, supporting the combined use of structural exams and functional tests as valid tools to detect the extent of RPE and photoreceptors' disruption.

Effectiveness and safety of ranibizumab 0.5 mg in treatment-naïve patients with diabetic macular edema: Results from the real-world global LUMINOUS study.

PURPOSE: To assess the one-year effectiveness and safety of ranibizumab 0.5 mg in treatment- naïve patients with diabetic macular edema (DME) enrolled in the real-world LUMINOUS study. PATIENTS AND METHODS: A 5-year, prospective, observational, open-label, global study which recruited 30,138 patients across all approved indications. Consenting patients (≥18 years) who were treatment-naïve or previously treated with ranibizumab or other ocular treatments were treated as per the local ranibizumab label. Here, we present the change in visual acuity (VA) (Early Treatment Diabetic Retinopathy Study letter score; primary treated eye) at Year 1, as well as the change in VA based on injection frequencies (≤4 and ≥5), treatment exposure, and the overall adverse events (AEs) and serious AEs (SAEs) in treatment-naïve DME patients. RESULTS: Of the 4,710 DME patients enrolled in the study, 1,063 were treatment-naïve. At baseline, mean age was 64.5 years, 54.7% were male, and 69.2% were white. At 1 year, mean VA letter score improved by +3.5 (n = 502) from a baseline of 57.7 with a mean of 4.5 injections. Presented by injection frequencies ≤4 and ≥5, VA letter score gains were 0.5 (n = 264) and 6.9 (n = 238) from baseline letter scores of 56.6 and 59.0, respectively. Over 5 years, the incidence of ocular/non-ocular AEs and SAEs was 7.2%/10.1% and 0.3%/5.8%, respectively. No endophthalmitis cases were reported. CONCLUSIONS: The LUMINOUS study included patients with DME with more diverse baseline characteristics than those in randomized clinical trials. The 1-year data showed improvement in VA with low number of injections in treatment- naïve patients with DME. Greater VA gains were observed in patients who received ≥5 injections. No new safety findings were identified. LUMINOUS confirms the effectiveness and safety of ranibizumab for the treatment of patients with DME in a real-world clinical practice.

Antioxidant Saffron and Central Retinal Function in ABCA4-Related Stargardt Macular Dystrophy.

Retinal oxidative damage, associated with an ATP-binding cassette, sub-family A, member 4, also known as ABCA4 gene mutation, has been implicated as a major underlying mechanism for Stargardt disease/fundus flavimaculatus (STG/FF). Recent findings indicate that saffron carotenoid constituents crocins and crocetin may counteract retinal oxidative damage, inflammation and protect retinal cells from apoptosis. This pilot study aimed to evaluate central retinal function following saffron supplementation in STG/FF patients carrying ABCA4 mutations. METHODS: in a randomized, double-blind, placebo-controlled study (clinicaltrials.gov: NCT01278277), 31 patients with ABCA4-related STG/FF and a visual acuity >0.25 were randomly assigned to assume oral saffron (20 mg) or placebo over a six month period and then reverted to P or S for a further six month period. Full ophthalmic examinations, as well as central 18° focal electroretinogram (fERG) recordings, were performed at baseline and after six months of either saffron or placebo. The fERG fundamental harmonic component was isolated by Fourier analysis. Main outcome measures were fERG amplitude (in µV) and phase (in degrees). The secondary outcome measure was visual acuity. RESULTS: supplement was well tolerated by all patients throughout follow-up. After saffron, fERG amplitude was unchanged; after placebo, amplitude tended to decrease from baseline (mean change: -0.18 log µV, p < 0.05). Reverting the treatments, amplitude did not change significantly. fERG phase and visual acuity were unchanged throughout follow-up. CONCLUSIONS: short-term saffron supplementation was well tolerated and had no detrimental effects on the electroretinographic responses of the central retina and visual acuity. The current findings warrant further long-term clinical trials to assess the efficacy of saffron supplementation in slowing down the progression of central retinal dysfunction in ABCA4-related STG/FF.

Sequential spectral domain optical coherence tomography imaging of an eye after successful removal of subfoveal perfluorcarbon liquid collection.

PURPOSE: To evaluate retinal restoration after subfoveal perfluorcarbon liquid (PFCL) bubble removal by means of autofluorescence, infrared, and spectral domain optical coherence tomography over 2 years of follow-up. METHODS: A 62-year-old patient underwent two 23-gauge vitrectomies in attempt to remove subretinal PFCL retained under the fovea secondary to retinal detachment surgery in the left eye. We assessed best-corrected visual acuity, fundus biomicroscopy, retinal imaging by autofluorescence, infrared, and spectral domain optical coherence tomography at the first observation of retained PFCL, 1 day after the first attempt of PFCL removal, and 1, 30, 90, and 180 days, and 2 years after the second successful removal surgery. RESULTS: The best-corrected visual acuity improved from 5 to 45 Early Treatment of Diabetic Retinopathy Study letters (1.0 to 0.2 logMAR units) at the end of follow-up. Spectral domain optical coherence tomography scans showed progressive reorganization of the outer limiting membrane and significant restoration of the inner/outer segment photoreceptors junction 2 years after surgery. CONCLUSION: Subfoveal PFCL is believed to cause photoreceptor damage in some eyes, probably because of mechanical compression. Innovative methods of imaging such as spectral domain optical coherence tomography and confocal scanning laser ophthalmoscope with infrared and autofluorescence, allow early and clear detection of subfoveal retained PFCL, as well as careful follow-up and easy differential diagnosis. Surgical removal leads to prompt retinal morphologic restoration and functional improvement enduring over time.

Macular functional changes evaluated with MP-1 microperimetry after intravitreal bevacizumab for subfoveal myopic choroidal neovascularization: one-year results.

PURPOSE: The purpose of this study was to evaluate 1-year functional and structural effects of intravitreal bevacizumab for subfoveal choroidal neovascularization secondary to pathologic myopia (myopic choroidal neovascularization). METHODS: Fifteen eyes with myopic choroidal neovascularization participated in this prospective interventional, noncomparative case series. All patients were treated with one intravitreal injection of 1.25 mg bevacizumab. Retreatments were performed in case of persistent or recurrent leakage on fluorescein angiography and/or intraretinal fluid on optical coherence tomography. Evaluation of best-corrected visual acuity using Early Treatment of Diabetic Retinopathy Study criteria, MP-1 microperimetry, optical coherence tomography, and fluorescein angiography were performed before treatment and 1 month, 3 months, 6 months, and 1 year after treatment. RESULTS: After a follow-up of 12 months, best-corrected visual acuity improved on average of 0.23 logarithm of the minimum angle of resolution. Mean macular sensitivity within the central 8 degrees increased on average of 2.62 dB at 12-month postinjection. The mean number of measurement points within the central absolute scotoma reduced significantly from 12.47 before treatment to 6.27 at 1-year follow-up. An improvement of fixation stability from baseline was observed in 9 patients (60%). No treatment adverse events were evidenced. CONCLUSION: Improvement of macular sensitivity and fixation stability 1 year after intravitreal bevacizumab for myopic choroidal neovascularization suggest a stable and progressive macular function recovery. The mean treatment session was 1.53, with 53.3% of patients needing only a single intravitreal bevacizumab injection, supporting a potential long-lasting efficacy of intravitreal bevacizumab treatment.

Intravitreal bevacizumab (Avastin) in proliferative diabetic retinopathy.

PURPOSE: To evaluate the efficacy and safety of intravitreal bevacizumab in proliferative diabetic retinopathy (PDR) patients. METHODS: This interventional case series study included 15 eyes of 10 patients with bilateral PDR: 13 eyes with severe PDR and active new vessels (NV) and two eyes with recurrent vitreous haemorrhages. Study eyes received a single intravitreal injection of 1.25 mg (0.05 ml) bevacizumab. All eyes were followed up for 3 months, and eight of them for 9 months. Reinjection was performed in three eyes 4-6 months after the first injection. Study eyes were evaluated by fluorescein angiography at baseline, 1, 3 and 9 months. Quantitative planimetric analysis (QPA) of NV area was measured before and after treatment. All eyes received or completed panretinal photocoagulation (PRP) 1 month after the first injection. RESULTS: As early as at 1 month, all study eyes had a regression (paired t-test, P = 0.01) of QPA-estimated NV area. The eyes with recurrent vitreous haemorrhages had clearing of bleeding. These early effects were maintained at 3 months for all eyes and tended to be stable at 9 months. The fast and measurable efficacy of bevacizumab allowed a subsequent complete and safe PRP. CONCLUSION: Intravitreal bevacizumab did not reveal any side-effects and was effective in the regression of NV areas and the resolution of vitreous haemorrhages. This approach is potentially useful in allowing (within a planned temporal window) a safe and efficient PRP to be performed while minimizing the risk of its complications.

Temporal response properties of the macular cone system: effect of normal aging and age-related maculopathy.

PURPOSE: To evaluate the influence of aging and age-related maculopathy (ARM) on the temporal frequency response function (TFR) of macular focal electroretinography. METHODS: Macular (18 degrees ) focal electroretinograms (FERGs) in response to sinusoidal flicker, modulated at TFs between 3.7 and 52 Hz, were recorded from 13 young (age range, 14-29 years) and 9 old (age range, 55-80 years) healthy subjects and from 18 patients with ARM (stage 2 disease; age range, 55-80 years; visual acuity >/=0.4). Amplitude and phase of the Fourier-analyzed response fundamental (1F) and seconnd harmonic (2F) were measured. RESULTS: In young healthy subjects, mean 1F TFR showed a maximum amplitude at 41 Hz, a secondary peak at 3.7 Hz, a minimum at 8 Hz, and a high TF (32-52 Hz) roll-off. Mean 1F TFR of old, compared with young, healthy subjects showed amplitude enhancement at 10 to 14 Hz and a small loss at high TF. Mean 2F TFR of young and old healthy subjects had a maximum at 5.7 to 8 Hz and an attenuation beyond 10 Hz. Mean 1F and 2F TFRs of ARM patients were similar to those of old healthy subjects but were depressed in mean amplitude. FERG TFR changes of old healthy subjects and ARM patients were not mimicked by reducing stimulus retinal illuminance or modulation depth in young healthy subjects. CONCLUSIONS: FERG temporal properties are affected by normal aging and ARM. Because FERG TFR is shaped mainly by postreceptoral activity, the findings suggest that photoreceptor and postsynaptic dysfunction underlie aging- and ARM-related FERG changes.