Age-Related Macular Degeneration: A Review.

Importance: Age-related macular degeneration (AMD) affects approximately 20 million people in the US and 196 million people worldwide. AMD is a leading cause of severe vision impairment in older people and is expected to affect approximately 288 million people worldwide by 2040. Observations: Older age, genetic factors, and environmental factors, such as cigarette smoking, are associated with development of AMD. AMD occurs when extracellular deposits accumulate in the outer retina, ultimately leading to photoreceptor degeneration and loss of central vision. The late stages of AMD are characterized by outer retinal atrophy, termed geographic atrophy, or neovascularization associated with subretinal and/or intraretinal exudation, termed exudative neovascular AMD. The annual incidence of AMD ranges from 0.3 per 1000 in people who are aged 55 to 59 years to 36.7 per 1000 in people aged 90 years or older. The estimated heritability of late-stage AMD is approximately 71% (95% CI, 18%-88%). Long-term prospective cohort studies show a significantly higher AMD incidence in people who smoke more than 20 cigarettes per day compared with people who never smoked. AMD is diagnosed primarily with clinical examination that includes a special lens that focuses light of the slit lamp through the pupil. Exudative neovascular AMD is best identified using angiography and by optical coherence tomography. Individuals with AMD who take nutritional supplements consisting of high-dose vitamin C, vitamin E, carotenoids, and zinc have a 20% probability to progress to late-stage AMD at 5 years vs a 28% probability for those taking a placebo. In exudative neovascular AMD, 94.6% of patients receiving monthly intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections experience less than a 15-letter visual acuity loss after 12 months compared with 62.2% receiving sham treatment. Conclusions and Relevance: The prevalence of AMD is anticipated to increase worldwide to 288 million individuals by 2040. Intravitreally administered anti-VEGF treatment is first-line therapy for exudative neovascular AMD.

AREDS2 Supplementation in Patients with Wet Age-Related Macular Degeneration.

BACKGROUND: In recent years, major progress has been made in treating the wet form of age-related macular degeneration (AMD) with anti-vascular endothelial growth factors, which reportedly stabilize and improve vision. OBJECTIVES: To examine the effect of dietary supplementation, as recommended by the Age-Related Eye Disease Study 2 (AREDS2), on the number of anti-vascular endothelial growth factor injections administered to patients with wet AMD. METHODS: A retrospective study was conducted with 57 participants (27 participants in the study group and 30 in the control group) receiving injections of anti-vascular endothelial growth factors. The study group received dietary supplements for at least one year before the treatment was initiated, while the control group did not. Primary outcome was the number of injections a patient received over a 3-year period. Secondary outcomes were central macular thickness and visual acuity. RESULTS: The average number of injections per patient after 3 years was 21.89 ± 7.85 in the study group and 26.00 ± 5.62 in the control group (P = 0.083). Final visual acuities were 0.45 ± 0.45 and 0.8 ± 0.73 (P = 0.09), and final central macular thicknesses were 288.26 ± 55.38 and 313.12 ± 107.36 (P = 0.38) in the study and control groups, respectively. CONCLUSIONS: The average number of injections after 3 years was lower in the study group, but this difference did not reach statistical significance. No statistically significant difference was found in final visual acuity or central macular thickness between the groups.

Controversies and Disparities in the Management of Age-Related Macular Degeneration.

Age-related macular degeneration is a leading cause of blindness in patients aged 50 years and older. Prior to the 21st century, there were no effective treatments for this devastating disease. However, the last 20 years have heralded the development of treatments for both the nonexudative and exudative forms. The invention of AREDS vitamin supplements and anti-VEGF therapies forever changed the treatment of dry and wet age-related macular degeneration, respectively. The rapid adoption and expansion of these vision preserving treatments has created controversy regarding their cost, burden of administration, development, and use of new technologies, genetic considerations, and observed societal disparities. Many of these controversies and disparities persist today and will require further research to resolve.

Onion ring sign on spectral domain optical coherence tomography in diabetic macular edema: Its evolution and outcomes.

PURPOSE: To report evolution and outcomes of hyperreflective crystalline deposit (HCD) on optical coherence tomography (OCT) in diabetic maculopathy (DM). METHODS: Patients with DM showing HCD on OCT for the first time between June 2017 and May 2021 were included in the study. Demographic, ophthalmic and OCT features were documented and analysed. Factors leading to the development of HCD and its effect on the functional outcome were analysed and described in this study. RESULTS: Sixty cases of HCD were identified in 45 (males -33; females - 12) patients for the first-time during the defined study period. Mean age of the eligible patients was 61.53 ± 8.19 years. Average duration of diabetes was 13.82 ± 7.38 years. Mean visual acuity of these patients was 0.902 ± 0.438 logMAR units (Snellen equivalent = 20/160). Patients with HCD showed subretinal hard exudates, were on anti-cholesterol medications (n = 36, 80%) and showed reduced visual acuity (20/160) if the HCD involved the fovea. The median time taken for the development of HCD was 28 months. Mean follow-up duration of the study was 26.19 ± 27.98 months. Persistence of HCD in all cases (n = 42, 100%) was noted at the last follow-up visit. CONCLUSION: Horizontal, single or multi-layered HCDs on OCT in DM represent intraretinal or subretinal cholesterol crystal precipitates evolving from the hard exudates identical to the "onion ring sign" seen in neovascular AMD. HCDs or CCs depict deranged lipid metabolism, chronic vascular leakage and can lead to substantial visual impairment if the fovea gets involved.

The management of neovascular age-related macular degeneration: A systematic literature review of patient-reported outcomes, patient mental health and caregiver burden.

PURPOSE: The aim of this systematic literature review was to describe patient-reported outcomes, mental health and caregiver burden in patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents in routine clinical practice. METHODS: Electronic searches were conducted in Embase and MEDLINE according to pre-defined criteria. RESULTS: Of 856 records identified, 63 met inclusion criteria. Depression or depressive symptoms were reported in up to 42% of patients with nAMD. Of 25/63 (40%) studies evaluating quality of life (QoL) and using various tools, eight studies reported composite National Eye Institute Visual Functioning Questionnaire scores following anti-VEGF treatment. Of these, seven reported a statistically significant improvement at the earliest time point measured (Month 3-12) and approximately 50% reported sustained QoL benefits at 12 months. In studies comparing the attributed or different regimens, the most important factor from the patient's perspective was the likelihood that a particular regimen would maintain vision. There was a preference towards treat and extend, which was associated with a perceived reduction in patient and caregiver burden, compared to fixed dosing. CONCLUSIONS: A coordinated holistic approach to patient care is key to optimizing patient well-being as well as visual outcomes. Further research regarding the patient-reported impact of nAMD management outside the trial setting (particularly international longitudinal studies) is warranted. Standardization of QoL studies would assist in establishing whether sustained QoL improvement, rather than prevention of QoL decline, should be a realistic expectation of treatment of nAMD in the longer term.

Using Advanced Bioinformatics Tools to Identify Novel Therapeutic Candidates for Age-Related Macular Degeneration.

Purpose: Age-related macular degeneration (AMD) is the most common cause of aging-related blindness in the developing world. Although medications can slow progressive wet AMD, currently, no drugs to treat dry-AMD are available. We use a systems or in silico biology analysis to identify chemicals and drugs approved by the Food and Drug Administration for other indications that can be used to treat and prevent AMD. Methods: We queried National Center for Biotechnology Information to identify genes associated with AMD, wet AMD, dry AMD, intermediate AMD, and geographic atrophy to date. We combined genes from various AMD subtypes to reflect distinct stages of disease. Enrichment analysis using the ToppGene platform predicted molecules that can influence AMD genes. Compounds without clinical indications or with deleterious effects were manually filtered. Results: We identified several drug/chemical classes that can affect multiple genes involved in AMD. The drugs predicted from this analysis include antidiabetics, lipid-lowering agents, and antioxidants, which could theoretically be repurposed for AMD. Metformin was identified as the drug with the strongest association with wet AMD genes and is among the top candidates in all dry AMD subtypes. Curcumin, statins, and antioxidants are also among the top drugs correlating with AMD-risk genes. Conclusions: We use a systematic computational process to discover potential therapeutic targets for AMD. Our systematic and unbiased approach can be used to guide targeted preclinical/clinical studies for AMD and other ocular diseases. Translational Relevance: Advanced bioinformatics models identify novel chemicals and approved drug candidates that can be efficacious for different subtypes of AMD.

Unravelling the therapeutic potential of IL-33 for atrophic AMD.

Age-related macular degeneration (AMD), a degenerative disease affecting the retinal pigment epithelium (RPE) and photoreceptors in the macula, is the leading cause of central blindness in the elderly. AMD progresses to advanced stages of the disease, atrophic AMD (aAMD), or in 15% of cases "wet" or neovascular AMD (nAMD), associated with substantial vision loss. Whilst there has been advancement in therapies treating nAMD, to date, there are no licenced effective treatments for the 85% affected by aAMD, with disease managed by changes to diet, vitamin supplements, and regular monitoring. AMD has a complex pathogenesis, involving highly integrated and common age-related disease pathways, including dysregulated complement/inflammation, impaired autophagy, and oxidative stress. The intricacy of AMD pathogenesis makes therapeutic development challenging and identifying a target that combats the converging disease pathways is essential to provide a globally effective treatment. Interleukin-33 is a cytokine, classically known for the proinflammatory role it plays in allergic disease. Recent evidence across degenerative and inflammatory disease conditions reveals a diverse immune-modulatory role for IL-33, with promising therapeutic potential. Here, we will review IL-33 function in disease and discuss the future potential for this homeostatic cytokine in treating AMD.

Ocular and Systemic Complement Activation during Anti-Vascular Endothelial Growth Factor Treatment and Age-Related Eye Disease Study 2 Dietary Supplementation in Neovascular Age-Related Macular Degeneration.

PURPOSE: The aim of this study was to investigate the influence of dietary supplementation using Age-Related Eye Disease Study 2 (AREDS2) on complement activation in patients with neovascular age-related macular degeneration (nAMD) under ongoing treatment. METHODS: In this prospective, single-center, controlled, open-label investigator-initiated trial, eligible nAMD patients were randomized at a ratio of 1:1 in 2 groups: those with and without dietary AREDS2 supplementation for 4 weeks. Zinc, plasma, and aqueous humor (AH) complement levels were quantified via enzyme-linked immunosorbent assays. RESULTS: Fifty of 62 enrolled patients completed the trial (AREDS2 n = 27, controls n = 23). Systemic zinc and complement levels were not different at baseline between the 2 groups (p > 0.1). At the final visit, systemic zinc levels were significantly higher in the AREDS2 group (10.16 ± 2.08 µmol/L; 8.66 ± 1.17 µmol/L; p = 0.007), whereas systemic and AH complement levels were not different (p > 0.1). In both groups, no significant change was observed in systemic levels of C3, C3a, FH, FI, and sC5b-9 (p > 0.1). Only systemic complement component Ba showed an increase from baseline to the end visit (p = 0.01). This increase was higher in the control group (p = 0.02) than in the AREDS2 group (p = 0.23). CONCLUSIONS: Short-term dietary AREDS2 supplementation leads to a significant increase in systemic zinc levels without any influence on complement activation levels.

Incidence of Macular Atrophy after Untreated Neovascular Age-Related Macular Degeneration: Age-Related Eye Disease Study Report 40.

PURPOSE: To report the natural history of untreated neovascular age-related macular degeneration (nAMD) regarding subsequent macular atrophy. DESIGN: Prospective cohort within a randomized, controlled trial of oral micronutrient supplements. PARTICIPANTS: Age-Related Eye Disease Study (AREDS) participants (55-80 years) who demonstrated nAMD during follow-up (1992-2005), prior to anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Color fundus photographs were collected at annual study visits and graded centrally for late age-related macular degeneration (AMD). Incident macular atrophy after nAMD was examined by Kaplan-Meier analysis and proportional hazards regression. MAIN OUTCOME MEASURES: Incident macular atrophy after nAMD. RESULTS: Of the 4757 AREDS participants, 708 eyes (627 participants) demonstrated nAMD during follow-up and were eligible. The cumulative risks of incident macular atrophy after untreated nAMD were 9.6% (standard error, 1.2%), 31.4% (standard error, 2.2%), 43.1% (standard error, 2.6%), and 61.5% (standard error, 4.3%) at 2, 5, 7, and 10 years, respectively. This corresponded to a linear risk of 6.5% per year. The cumulative risk of central involvement was 30.4% (standard error, 3.2%), 43.4% (standard error, 3.8%), and 57.0% (standard error, 4.8%) at first appearance of atrophy, 2 years, and 5 years, respectively. Geographic atrophy (GA) in the fellow eye was associated with increased risk of macular atrophy (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.17-2.49; P = 0.006). However, higher 52-single nucleotide polymorphism AMD genetic risk score was not associated with increased risk of macular atrophy (HR, 1.03; 95% CI, 0.90-1.17; P = 0.67). Similarly, no significant differences were observed according to SNPs at CFH, ARMS2, or C3. CONCLUSIONS: The rate of incident macular atrophy after untreated nAMD is relatively high, increasing linearly over time and affecting half of eyes by 8 years. Hence, factors other than anti-VEGF therapy are involved in atrophy development, including natural progression to GA. Comparison with studies of treated nAMD suggests it may not be necessary to invoke a large effect of anti-VEGF therapy on inciting macular atrophy, although a contribution remains possible. Central involvement is present in one third of eyes at the outset (similar to pure GA) and increases linearly to half at 3 years.

Visual Acuity Outcomes after Anti-Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration: Age-Related Eye Disease Study 2 Report Number 19.

PURPOSE: To analyze best-corrected visual acuity (BCVA) outcomes after anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (AMD). DESIGN: Prospective cohort study of participants enrolled in a clinical trial of oral supplements and receiving anti-VEGF therapy in routine clinical practice. PARTICIPANTS: Age-Related Eye Disease Study 2 (AREDS2) participants (50-85 years of age) whose eyes met AREDS2 inclusion criteria at baseline (no late AMD, BCVA ≥20/100, no previous anti-VEGF injections) but received at least 1 anti-VEGF injection for incident neovascular AMD during follow-up. METHODS: Participants underwent refracted BCVA testing, ophthalmoscopic examination, and stereoscopic color fundus photography at baseline and annual study visits over 5 years. Self-reports of anti-VEGF injections (numbers, dates, and names of drug) were collected at baseline and annual study visits and during telephone calls every 6 months. MAIN OUTCOME MEASURES: Primary outcome measures were mean refracted BCVA and proportions of eyes with BCVA of 20/40 or better and 20/200 or worse. An exploratory outcome measure was the mean number of self-reported anti-VEGF injections. RESULTS: One thousand one hundred five eyes of 986 AREDS2 participants met the inclusion criteria; of these, 977 participants (99.1%) underwent at least 1 posttreatment visit. At the first and subsequent annual examinations after the first injection, mean refracted BCVAs were 68.0 letters (Snellen equivalent, 20/40), 66.1 letters, 64.7 letters, 63.2 letters, and 61.5 letters (Snellen equivalent, 20/60). Proportions of eyes with BCVA of 20/40 or better were 59.3%, 55.1%, 53.5%, 50.6%, and 49.7%, and those with BCVA of 20/200 or worse were 5.5%, 8.6%, 9.4%, 12.4%, and 14.4%. Mean annual numbers of self-reported anti-VEGF injections per eye were 2.9, 3.9, 3.3, 3.1, and 3.0. CONCLUSIONS: Refracted BCVA data were obtained in a clinical trial environment but were related to anti-VEGF treatment administered in normal clinical practice. Visual outcomes declined slowly with increased follow-up time: mean BCVA decreased by approximately 1.5 to 2 letters per year. At 5 years, half of eyes achieved BCVA of 20/40 or better, but approximately one sixth showed BCVA of 20/200 or worse. These data may be useful in assessing the long-term effects of anti-VEGF therapy.

Priority options of anti-vascular endothelial growth factor agents in wet age-related macular degeneration under the National Health Insurance Program.

BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of blindness worldwide, for which intravitreal injection of anti-vascular endothelial growth factor (VEGF) is the primary treatment option. The purpose of the current study was to investigate the prioritization of anti-VEGF agents for wet AMD under the National Health Insurance (NHI) Program, and their clinical outcomes. METHODS: Patients who were diagnosed with active choroidal neovascularization caused by AMD, and who met the criteria for reimbursement for anti-VEGF therapy by the NHI program in Taiwan between August 1, 2014 and May 31, 2015, were included in the study. Factors potentially influencing the choice of treatment agent were analyzed, and clinical outcomes were compared between the two different agents and their protocols. RESULTS: A total of 166 treatment applications in 166 eyes from 159 patients were enrolled in the study. Age, laterality, presence of retinal pigment epithelial detachment, history of hypertension, coronary artery disease, and cerebral vascular accidents were significantly associated with the selection of the anti-VEGF agent. Treatment patterns and clinical outcomes were similar between the patients treated with ranibizumab and those treated with aflibercept. Significantly fewer injections were given during the follow-up period in those treated with aflibercept. CONCLUSION: Under the restrictive insurance program in Taiwan, more patients and ophthalmologists chose to treat wet AMD using aflibercept. However, in clinical practice, no significant differences in efficacy or clinical outcomes were found between the patients treated with ranibizumab and those treated with aflibercept.

Telemedicine in the Management of Exudative Age-Related Macular Degeneration within an Integrated health care System.

PURPOSE: To investigate the outcomes of patients with exudative age-related macular degeneration (AMD) treated with intravitreal antivascular endothelial growth factors (VEGF) using a telemedicine system. DESIGN: Interventional case series. METHODS: This study examined all patients with exudative AMD who were receiving intravitreal anti-VEGF injections from September 1, 2015, through August 31, 2017, using electronic consultations at a single academic center and health system. Patients were managed initially by a retinal specialist and then allowed to receive further care with their local ophthalmologist. There were 200 electronic consultations placed during this time period for 83 eyes of 59 patients. Data collected included the retina specialist's recommendations: intravitreal agent, interval between injections, number of injections, and when the patient was to follow-up. All occurrences of recommendations that were not completed were reported. RESULTS: The mean age of the patients at the time of electronic consultations was 82.3 ± 7.3 years with a mean follow-up time of 2.4 ± 0.81 years. The mean distance from the home of the patient to the retina specialist was 70 ± 44 miles. There were 14 consultations (7.1%) that did not comply with the recommendations of the retina specialist. Most of these were due to other medical comorbidities leading to missed appointments or scheduling errors. CONCLUSIONS: In an integrated health care setting, 59 patients with exudative AMD were identified who were able to be effectively managed using a telemedicine system. In the appropriate setting, telemedicine may be able to assist in the management of patients with wet AMD.

Incidence of exudative age-related macular degeneration and treatment load under the Korean national health insurance system in 2010-2015.

BACKGROUND/AIM: The aim of this study was to estimate the nationwide incidence of clinically diagnosed exudative age-related macular degeneration (AMD) and associated use of ranibizumab and aflibercept in South Korea. METHODS: In this retrospective, population-based cohort study, claims data for 2010-2015 were analysed in a randomly selected sample of 519 661 adults aged ≥40 years. The incidence per 10 000 person-years was estimated, along with the 95% CI. Incident exudative AMD was defined based on the registration code for rare intractable diseases. Use of ranibizumab and aflibercept and the incidence of exudative AMD were recorded. RESULTS: Nine hundred and twelve patients were newly diagnosed with exudative AMD in 2010-2015. The 6-year incidence in the general population aged ≥40 years was 2.9 (95% CI 2.8 to 3.0) per 10 000 person-years. The incidence was highest in individuals aged 75-79 years (12.0, 95% CI 10.3 to 13.8). The incidence was higher in men than in women in all age groups. Six hundred and twenty-five (69%) of the 912 newly diagnosed patients started ranibizumab or aflibercept as a first-line treatment. The average number of injections administered was 6.1 (SD 3.9; minimum of 1 injection and maximum government-supported limit of 14) during 2010-2015; the number increased with increasing government funding support (from 5 to 10 and from 10 to 14 in 2013 and 2014, respectively). CONCLUSIONS: This study describes the incidence of exudative AMD in South Korea and its treatment under the national health insurance system in this country. Its findings could be used for reference purposes and be useful when planning treatment for exudative AMD.

ASSOCIATION BETWEEN ORAL IRON SUPPLEMENTATION AND RETINAL OR SUBRETINAL HEMORRHAGE IN THE COMPARISON OF AGE-RELATED MACULAR DEGENERATION TREATMENT TRIALS.

PURPOSE: Because patients often take iron supplements without medical indication, and iron can accumulate in vascular endothelial cells, the authors evaluated the association of oral iron supplementation with retinal/subretinal hemorrhage in patients with neovascular age-related macular degeneration. METHODS: A post hoc secondary data analysis of comparison of age-related macular degeneration treatments trials was performed. Participants were interviewed for use of oral iron supplements. Trained readers evaluated retinal/subretinal hemorrhage in baseline fundus photographs. Adjusted odds ratios from multivariate logistic regression models assessed the association between iron use and baseline hemorrhage adjusted by age, sex, smoking, hypertension, anemia, and use of antiplatelet/anticoagulant drugs. RESULTS: Among 1,165 participants, baseline retinal/subretinal hemorrhage was present in the study eye in 71% of 181 iron users and in 61% of 984 participants without iron use (adjusted odds ratio = 1.47, P = 0.04), and the association was dose dependent (adjusted linear trend P = 0.048). Iron use was associated with hemorrhage in participants with hypertension (adjusted odds ratio = 1.87, P = 0.006) but not without hypertension. The association of iron use with hemorrhage remained significant among hypertensive participants without anemia (adjusted odds ratio = 1.85, P = 0.02). CONCLUSION: Among participants of comparison of age-related macular degeneration treatments trials, the use of oral iron supplements was associated with retinal/subretinal hemorrhage in a dose-response manner. Unindicated iron supplementation may be detrimental in patients with wet age-related macular degeneration.

Repeated intravitreal injections of antivascular endothelial growth factor in patients with neovascular age-related macular degeneration may increase the risk of ischemic optic neuropathy.

BACKGROUND: Previous case reports have demonstrated the occurrence of ischemic optic neuropathy (ION) following intravitreal injections of antivascular endothelial growth factor (anti-VEGF). However, no previous studies have investigated the impact of injection numbers on the risk of ION. The aim of our study was to investigate whether repeated intravitreal injections of anti-VEGF would increase the risk of subsequent ION in patients with neovascular age-related macular degeneration (AMD). METHODS: A population-based, retrospective cohort study using the Taiwan National Health Insurance Research Database was conducted from 2007 to 2013. Neovascular AMD patients receiving intravitreal injections of anti-VEGF during the study period were enrolled in the study cohort. Enrollees were divided into three groups according to the categorized levels of injection number (first level: < 10 times, second level: 10-15 times, and third level: > 15 times). Kaplan-Meier curves were generated to compare the cumulative hazard of subsequent ION among the three groups. Cox regression analyses were used to estimate crude and adjusted hazard ratios (HRs) for ION development with respect to the different levels of injection numbers. The confounders included for adjustment were age, sex, and comorbidities (diabetes, hypertension, hyperlipidemia, ischemic heart disease, and glaucoma). RESULTS: In total, the study cohort included 77,210 patients. Of these, 26,520, 38,010, and 12,680 were in the first-, second-, and third-level groups, respectively. The Kaplan-Meier method revealed that the cumulative hazards of ION were significantly higher in those who had a higher injection number. After adjusting for confounders, the adjusted HRs for ION in the second- and third-level groups were 1.91 (95% confidence interval [CI], 1.32-2.76) and 2.20 (95% CI, 1.42-3.43), respectively, compared with those in the first-level group. CONCLUSIONS: Among patients with neovascular AMD, those who receive a higher number of anti-VEGF injections have a significantly higher risk of developing ION compared with individuals who receive a lower number of injections.

Conbercept for patients with age-related macular degeneration: a systematic review.

BACKGROUND: Conbercept is a novel vascular endothelial growth factor (VEGF) inhibitor for the treatment of wet age-related macular degeneration (AMD). This systematic review aims to assess the efficacy and safety of conbercept in the treatment of wet AMD. METHODS: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP database, and Wanfang database were searched from their earliest records to June 2017. We included randomized controlled trials (RCTs) evaluating the efficacy and safety of conbercept in wet AMD patients. Outcomes included the mean changes from baseline in best-corrected visual acuity (BCVA) score (primary outcome), central retinal thickness (CRT), plasma level of vascular endothelial growth factor (VEGF) over time, and the incidence of adverse events (AEs). RESULTS: Eighteen RCTs (1285 participants) were included in this systematic review. Conbercept might improve BCVA compared to triamcinolone acetonide [MD = 0.11, 95% CI (0.08, 0.15)], and reduce CRT compared to the other four therapies (conservative treatment, ranibizumab, transpupillary thermotherapy, and triamcinolone acetonide). The incidence of AEs in patients receiving conbercept was significantly lower than those receiving triamcinolone acetonide [RR = 0.25, 95% CI (0.09-0.72)], but was similar to the other therapies. Conbercept seemed to be more effective than ranibizumab in lowering the plasma level of VEGF [MD = - 15.86, 95% CI (- 23.17, - 8.55)]. CONCLUSIONS: Current evidence shows that conbercept is a promising option for the treatment of wet AMD. Nevertheless, further studies are required to compare the efficacy, long-term safety and cost-effectiveness between conbercept and other anti-VEGF agents in different populations.

Effect of Dietary Supplementation With Lutein, Zeaxanthin, and ω-3 on Macular Pigment: A Randomized Clinical Trial.

Importance: Nutritional uptake of lutein, zeaxanthin, and ω-3 polyunsaturated fatty acids may increase macular pigment optical density (MPOD) and thereby protect against the development of age-related macular degeneration (AMD). Objectives: To estimate the efficiency of dietary supplementation containing lutein, zeaxanthin, ω-3 polyunsaturated fatty acids, and vitamins to increase the density of macular pigment in first-generation offspring of parents with neovascular AMD. Design, Setting, and Participants: This study was a randomized clinical trial (Lutein Influence on Macula of Persons Issued From AMD Parents [LIMPIA]) with a 6-month treatment period, followed by a 6-month follow-up period. Analyses were based on the intent-to-treat principle. The setting was 2 university hospitals in France (at Bordeaux and Dijon) from January 2011 (first participant first visit) to February 2013 (last participant last visit). The analysis was conducted from January to November 2016. Participants were 120 individuals free of any retinal ocular disease. They were first-generation offspring of parents with neovascular AMD. Interventions: Participants were randomized in a 1:1 ratio to receive either 2 daily dietary supplementation capsules or placebo for 6 months. Main Outcomes and Measures: The primary assessment criterion was the evolution of MPOD after 6 months of supplementation (value of both eligible eyes) measured using the modified MPD-Visucam 200 (Carl Zeiss Meditec) and the modified Heidelberg Retina Angiograph (Heidelberg Engineering) (HRA) at 0.98° eccentricity. The statistical analysis was adjusted for hospital and for risk factors. Results: Overall, 120 participants (60 in each group) were included, and 239 eyes were analyzed (119 in the lutein plus zeaxanthin [L + Z] group and 120 in the placebo group). Their mean (SD) age was 56.7 (6.6) years, and 71.7% (n = 86) were female. A statistically significant increase in plasma lutein and zeaxanthin was shown in the L + Z group after 3 months and 6 months of treatment compared with the placebo group. However, the difference between groups in the evolution of MPOD measured by HRA 0.98° eccentricity between 6 months and baseline was 0.036 (95% CI, -0.037 to 0.110) (P = .33). Conclusions and Relevance: Among first-generation offspring of parents with neovascular AMD in the LIMPIA trial, MPOD as measured with the modified HRA and the MPD-Visucam was not modified after 6 months of lutein and zeaxanthin dietary supplementation despite plasma levels showing continuous exposure to lutein and zeaxanthin. Further research is necessary to understand the mechanism of absorption and metabolism of these nutrients in the macula, the best way to measure MPOD, and the clinical benefit for the patients. Trial Registration: clinicaltrials.gov Identifier: NCT01269697.

Epilutein for Early-Stage Age-Related Macular Degeneration: A Randomized and Prospective Study.

PURPOSE: The hypothesis that oral supplementation of the epilutein/lutein combination could augment the macular pigment optical density (MPOD) in patients with age-related macular degeneration (AMD) was tested. METHODS: In a prospective randomized interventional study, 40 consecutive patients with early-stage AMD were recruited. After a 2-week run-in period, patients were randomly treated with a daily oral administration of 8 mg epilutein and 2 mg lutein (group 1) or 10 mg lutein (group 2) for 2 months. At baseline (BL) and 1-month (M1) and 2-month visits (M2), all patients underwent a complete ophthalmological examination, including measurement of MPOD in a 7° area (Visucam 200; Carl Zeiss Meditec, Milan, Italy). Xanthophylls were quantified in plasma, as well as the HDL, non-HDL, and erythrocyte fractions at each study visit. RESULTS: Twenty-one patients (mean age 69.4 ± 6.7 years, 35 eyes) were included in group 1. Mean MPOD was 0.203 ± 0.02 optical density units (ODU) at BL, and increased to 0.214 ± 0.04 ODU at M1 (p = 0.008) and 0.206 ± 0.03 ODU at M2 (p = 0.04). Sixteen patients (mean age 72.0 ± 6.3 years, 29 eyes) were included in group 2. Mean MPOD was 0.215 ± 0.03 at BL, which reduced to 0.202 ± 0.03 ODU at M1 (p = 0.003) and 0.207 ± 0.02 ODU at M2 (p < 0.001). A rise in the systemic level of total xanthophylls was observed at M1 for both groups. At M2, total xanthophylls were significantly increased only in group 1 and decreased in group 2. CONCLUSION: In patients with early-stage AMD, the administration of lutein in combination with epilutein was associated with an increased MPOD compared to the administration of lutein alone.

Recent developments in age-related macular degeneration: a review.

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.