Sharifi S, Sharifi H, Akbari A, Lei F, Dohlman CH, Gonzalez-Andrades M, Guild C, Paschalis EI, Chodosh J. Critical media attributes in E-beam sterilization of corneal tissue. Acta Biomater 2022;138:218-227.Abstract
When ionizing irradiation interacts with a media, it can form reactive species that can react with the constituents of the system, leading to eradication of bioburden and sterilization of the tissue. Understanding the media's properties such as polarity is important to control and direct those reactive species to perform desired reactions. Using ethanol as a polarity modifier of water, we herein generated a series of media with varying relative polarities for electron beam (E-beam) irradiation of cornea at 25 kGy and studied how the irradiation media's polarity impacts properties of the cornea. After irradiation of corneal tissues, mechanical (tensile strength and modulus, elongation at break, and compression modulus), chemical, optical, structural, degradation, and biological properties of the corneal tissues were evaluated. Our study showed that irradiation in lower relative polarity media improved structural properties of the tissues yet reduced optical transmission; higher relative polarity reduced structural and optical properties of the cornea; and intermediate relative polarity (ethanol concentrations = 20-30% (v/v)) improved the structural properties, without compromising optical characteristics. Regardless of media polarity, irradiation did not negatively impact the biocompatibility of the corneal tissue. Our data shows that the absorbed ethanol can be flushed from the irradiated cornea to levels that are nontoxic to corneal and retinal cells. These findings suggest that the relative polarity of the irradiation media can be tuned to generate sterilized tissues, including corneal grafts, with engineered properties that are required for specific biomedical applications. STATEMENT OF SIGNIFICANCE: Extending the shelf-life of corneal tissue can improve general accessibility of cornea grafts for transplantation. Irradiation of donor corneas with E-beam is an emerging technology to sterilize the corneal tissues and enable their long-term storage at room temperature. Despite recent applications in clinical medicine, little is known about the effect of irradiation and preservation media's characteristics, such as polarity on the properties of irradiated corneas. Here, we have showed that the polarity of the media can be a valuable tool to change and control the properties of the irradiated tissue for transplantation.
Su T, Zhu P-W, Li B, Shi W-Q, Lin Q, Yuan Q, Jiang N, Pei C-G, Shao Y. Gray matter volume alterations in patients with strabismus and amblyopia: voxel-based morphometry study. Sci Rep 2022;12(1):458.Abstract
This study proposes the use of the voxel-based morphometry (VBM) technique to investigate structural alterations of the cerebral cortex in patients with strabismus and amblyopia (SA). Sixteen patients with SA and sixteen healthy controls (HCs) underwent magnetic resonance imaging. Original whole brain images were analyzed using the VBM method. Pearson correlation analysis was performed to evaluate the relationship between mean gray matter volume (GMV) and clinical manifestations. Receiver operating characteristic (ROC) curve analysis was applied to classify the mean GMV values of the SA group and HCs. Compared with the HCs, GMV values in the SA group showed a significant difference in the right superior temporal gyrus, posterior and anterior lobes of the cerebellum, bilateral parahippocampal gyrus, and left anterior cingulate cortex. The mean GMV value in the right superior temporal gyrus, posterior and anterior lobes of the cerebellum, and bilateral parahippocampal gyrus were negatively correlated with the angle of strabismus. The ROC curve analysis of each cerebral region confirmed the accuracy of the area under the curve. Patients with SA have reduced GMV values in some brain regions. These findings might help to reveal the potential pathogenesis of SA and its relationship with the atrophy of specific regions of the brain.
Kruijt CC, Gradstein L, Bergen AA, Florijn RJ, Arveiler B, Lasseaux E, Zanlonghi X, Bagdonaite-Bejarano L, Fulton AB, Yahalom C, Blumenfeld A, Perez Y, Birk OS, de Wit GC, Schalij-Delfos NE, van Genderen MM. The Phenotypic and Mutational Spectrum of the FHONDA Syndrome and Oculocutaneous Albinism: Similarities and Differences. Invest Ophthalmol Vis Sci 2022;63(1):19.Abstract
Purpose: The purpose of this study was to further expand the mutational spectrum of the Foveal Hypoplasia, Optic Nerve Decussation defect, and Anterior segment abnormalities (FHONDA syndrome), to describe the phenotypic spectrum, and to compare it to albinism. Subjects and Methods: We retrospectively collected molecular, ophthalmic, and electrophysiological data of 28 patients molecularly confirmed with FHONDA from the Netherlands (9), Israel (13), France (2), and the United States of America (4). We compared the data to that of 133 Dutch patients with the 3 most common types of albinism in the Netherlands: oculocutaneous albinism type 1 (49), type 2 (41), and ocular albinism (43). Results: Patients with FHONDA had a total of 15 different mutations in SLC38A8, of which 6 were novel. Excluding missing data, all patients had moderate to severe visual impairment (median visual acuity [VA] = 0.7 logMAR, interquartile range [IQR] = 0.6-0.8), nystagmus (28/28), and grade 4 foveal hypoplasia (17/17). Misrouting was present in all nine tested patients. None of the patients had any signs of hypopigmentation of skin and hair. VA in albinism was better (median = 0.5 logMAR, IQR = 0.3-0.7, P 0.006) and the phenotypes were more variable: 14 of 132 without nystagmus, foveal hypoplasia grades 1 to 4, and misrouting absent in 16 of 74. Conclusions: Compared to albinism, the FHONDA syndrome appears to have a more narrow phenotypic spectrum, consisting of nonprogressive moderately to severely reduced VA, nystagmus, severe foveal hypoplasia, and misrouting. The co-occurrence of nystagmus, foveal hypoplasia, and misrouting in the absence of hypopigmentation implies that these abnormalities are not caused by lack of melanin, which has important implications for understanding the pathogenesis of these features.
Xiao S, Angjeli E, Wu HC, Gaier ED, Gomez S, Travers DA, Binenbaum G, Langer R, Hunter DG, Repka MX, Repka MX. Randomized Controlled Trial of a Dichoptic Digital Therapeutic for Amblyopia. Ophthalmology 2022;129(1):77-85.Abstract
PURPOSE: Digital therapeutics are a new class of interventions that are software driven and are intended to treat various conditions. We developed and evaluated a dichoptic digital therapeutic for amblyopia, a neurodevelopmental disorder for which current treatments may be limited by poor adherence and residual vision deficits. DESIGN: Randomized controlled trial. PARTICIPANTS: One hundred five children 4 to 7 years of age with amblyopia were enrolled at 21 academic and community sites in the United States. Participants were randomized 1:1 to the treatment or comparison group, stratified by site. METHODS: We conducted a phase 3 randomized controlled trial to evaluate the safety and efficacy of a dichoptic digital therapeutic for amblyopia. Participants in the treatment group used the therapeutic at home for 1 hour per day, 6 days per week and wore glasses full-time. Participants in the comparison group continued wearing glasses full-time alone. MAIN OUTCOME MEASURES: The primary efficacy outcome was change in amblyopic eye visual acuity (VA) from baseline at 12 weeks, and VA was measured by masked examiners. Safety was evaluated using the frequency and severity of study-related adverse events. Primary analyses were conducted using the intention-to-treat population. RESULTS: Between January 16, 2019, and January 15, 2020, 105 participants were enrolled; 51 were randomized to the treatment group and 54 were randomized to the comparison group. At 12 weeks, amblyopic eye VA improved by 1.8 lines (95% confidence interval [CI], 1.4-2.3 lines; n = 45) in the treatment group and by 0.8 lines (95% CI, 0.4-1.3 lines; n = 45) in the comparison group. At the planned interim analysis (adjusted α = 0.0193), the difference between groups was significant (1.0 lines; P = 0.0011; 96.14% CI, 0.33-1.63 lines) and the study was stopped early for success, according to the protocol. No serious adverse events were reported. CONCLUSIONS: Our findings support the value of the therapeutic in clinical practice as an effective treatment. Future studies should evaluate the therapeutic compared with other methods and in additional patient populations.
Wykoff CC, Abreu F, Adamis AP, Basu K, Eichenbaum DA, Haskova Z, Lin H, Loewenstein A, Mohan S, Pearce IA, Sakamoto T, Schlottmann PG, Silverman D, Sun JK, Wells JA, Willis JR, Tadayoni R, and Investigators YOSEMITERHINE. Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials. Lancet 2022;399(10326):741-755.Abstract
BACKGROUND: To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody. METHODS: YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6·0 mg every 8 weeks, faricimab 6·0 mg per personalised treatment interval (PTI), or aflibercept 2·0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with (YOSEMITE NCT03622580 and RHINE NCT03622593). FINDINGS: 3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10·7 ETDRS letters [97·52% CI 9·4 to 12·0] vs 10·9 ETDRS letters [9·6 to 12·2], difference -0·2 ETDRS letters [-2·0 to 1·6]; RHINE 11·8 ETDRS letters [10·6 to 13·0] vs 10·3 ETDRS letters [9·1 to 11·4] letters, difference 1·5 ETDRS letters [-0·1 to 3·2]) and faricimab PTI (YOSEMITE 11·6 ETDRS letters [10·3 to 12·9], difference 0·7 ETDRS letters [-1·1 to 2·5]; RHINE 10·8 ETDRS letters [9·6 to 11·9], difference 0·5 ETDRS letters [-1·1 to 2·1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31%], RHINE n=137 [43%]), faricimab PTI (n=106 [34%], n=119 [37%]), and aflibercept every 8 weeks (n=102 [33%], n=113 [36%]). INTERPRETATION: Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema. FUNDING: F Hoffmann-La Roche.
Simcoe MJ, Shah A, Fan BJ, Choquet H, Weisschuh N, Waseem NH, Jiang C, Melles RB, Ritch R, Mahroo OA, Wissinger B, Jorgenson E, Wiggs JL, Garway-Heath DF, Hysi PG, Hammond CJ. Genome-Wide Association Study Identifies Two Common Loci Associated with Pigment Dispersion Syndrome/Pigmentary Glaucoma and Implicates Myopia in its Development. Ophthalmology 2022;129(6):626-636.Abstract
PURPOSE: To identify genetic variants associated with pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG) in unrelated patients and to further understand the genetic and potentially causal relationships between PDS and associated risk factors. DESIGN: A 2-stage genome-wide association meta-analysis with replication and subsequent in silico analyses including Mendelian randomization. PARTICIPANTS: A total of 574 cases with PG or PDS and 52 627 controls of European descent. METHODS: Genome-wide association analyses were performed in 4 cohorts and meta-analyzed in 3 stages: (1) a discovery meta-analysis was performed in 3 cohorts, (2) replication was performed in the fourth cohort, and (3) all 4 cohorts were meta-analyzed to increase statistical power. Two-sample Mendelian randomization was used to determine whether refractive error and intraocular pressure exert causal effects over PDS. MAIN OUTCOME MEASURES: The association of genetic variants with PDS and whether myopia exerts causal effects over PDS. RESULTS: Significant association was present at 2 novel loci for PDS/PG. These loci and follow-up analyses implicate the genes gamma secretase activator protein (GSAP) (lead single nucleotide polymorphism [SNP]: rs9641220, P = 6.0×10-10) and glutamate metabotropic receptor 5 (GRM5)/TYR (lead SNP: rs661177, P = 3.9×10-9) as important factors in disease risk. Mendelian randomization showed significant evidence that negative refractive error (myopia) exerts a direct causal effect over PDS (P = 8.86×10-7). CONCLUSIONS: Common SNPs relating to the GSAP and GRM5/TYR genes are associated risk factors for the development of PDS and PG. Although myopia is a known risk factor, this study uses genetic data to demonstrate that myopia is, in part, a cause of PDS and PG.
West ER, Lapan SW, Lee C, Kajderowicz KM, Li X, Cepko CL. Spatiotemporal patterns of neuronal subtype genesis suggest hierarchical development of retinal diversity. Cell Rep 2022;38(1):110191.Abstract
How do neuronal subtypes emerge during development? Recent molecular studies have profiled existing neuronal diversity, but neuronal subtype genesis remains elusive. The 15 types of mouse retinal bipolar interneurons are characterized by distinct functions, morphologies, and transcriptional profiles. Here, we develop a comprehensive spatiotemporal map of bipolar subtype genesis in the murine retina. Combining multiplexed detection of 16 RNA markers with timed delivery of 5-ethynyl uridine (EdU) and bromodeoxyuridine (BrdU), we analyze more than 30,000 single cells in full retinal sections to classify all bipolar subtypes and their birthdates. We find that bipolar subtype birthdates are ordered and follow a centrifugal developmental axis. Spatial analysis reveals a striking wave pattern of bipolar subtype birthdates, and lineage analyses suggest clonal restriction on homotypic subtype production. These results inspire a hierarchical developmental model, with ordered subtype genesis within lineages. Our results provide insight into neuronal subtype development and establish a framework for studying subtype diversification.
Wu F, McGarrey MP, Geenen KR, Skalet AH, Guillot FH, Wilson JL, Shah AS, Gonzalez E, Thiele EA, Kim IK, Aronow ME. Treatment of Aggressive Retinal Astrocytic Hamartoma with Oral Mechanistic Target of Rapamycin Inhibition. Ophthalmol Retina 2022;6(5):411-420.Abstract
PURPOSE: To describe the clinical course and outcomes of aggressive retinal astrocytic hamartoma (RAH) treated with oral mechanistic target of rapamycin inhibitors (mTORis). DESIGN: A retrospective clinical case series. PARTICIPANTS: Five patients with genetically confirmed tuberous sclerosis complex and visually significant RAH due to tumor growth or exudation. METHODS: In this retrospective clinical case series, a review of electronic medical records was performed to determine baseline and follow-up ophthalmic examination characteristics, along with ancillary imaging findings, in patients receiving off-label treatment with either oral sirolimus or everolimus for symptomatic RAH. MAIN OUTCOME MEASURES: Visual acuity, change in tumor size, degree of exudation, and adverse effects of the mTORis were evaluated. RESULTS: The 5 patients in this series ranged in age from 8 months to 54 years. Four were treated with sirolimus, and 1 received everolimus. In all the cases, the tumor height was stable or decreased after the treatment (median follow-up duration, 39 months; range, 11-73 months). Exudation improved after the treatment in all the cases. In an 8-month-old infant, frequent upper respiratory tract infections prompted the cessation of treatment. In 1 patient, the mTORi was temporarily withheld because of elevated liver enzyme levels. No other significant adverse effects were noted. CONCLUSIONS: Sirolimus and everolimus should be considered in the management of vision-threatening RAH, particularly in the setting of exudative and rapidly growing tumors. Four of the 5 patients in this series tolerated the oral mTORi and continued with the therapy. There were no serious complications.
Qureshi S, Ferguson TJ, Lim M, You JY, Goshe JM, Hood CT. Acute Calcific Band Keratopathy as an Adverse Effect of Recombinant Human Nerve Growth Factor (Cenegermin): A Multicenter Case Series. Cornea 2022;41(1):52-59.Abstract
PURPOSE: Cenegermin, (OXERVATE) a recently Food and Drug Administration-approved topical formulation of recombinant human nerve growth factor, has been used for the treatment of neurotrophic keratopathy (NK). Corneal deposits have been previously reported as a potential adverse effect; however, the clinical characteristics, visual significance, and treatment options have not been fully described. The purpose of this article is to better characterize corneal deposits occurring during treatment with cenegermin for neurotrophic keratopathy. METHODS: This was a retrospective, multicenter consecutive case series. RESULTS: We identified 5 patients from 3 institutions who developed a white opacity in varying layers of the cornea, consistent with calcium deposition, during treatment with cenegermin. In all cases, the opacity occurred rapidly over the course of a few weeks after initiation of treatment. Histopathologic examination of the cornea from one corneal patient demonstrated extensive calcification of the stroma extending to 90% depth. Before treatment, all patients had stage 2 or 3 NK (Mackie classification). The deposits were visually significant in all patients and did not resolve after cessation of cenegermin. There were no differences in age, sex, etiology of the NK, corneal transplant status, or concurrent medications between the patients who developed a deposit and 15 other patients with stage 2 or 3 NK who did not. One patient was successfully treated with superficial keratectomy with ethylenediaminetetraacetic acid chelation, one patient underwent penetrating keratoplasty, and one patient received a Boston keratoprosthesis. CONCLUSIONS: We report the rapid onset of a corneal opacity after initiation of treatment with cenegermin in patients with stage 2 or 3 NK, consistent with acute calcific band keratopathy. This visually significant adverse finding has not previously been described. We could not identify any risk factors for development. We recommend close monitoring of patients receiving cenegermin therapy because the opacity may be irreversible and may require keratoplasty for visual rehabilitation.
Ramke J, Evans JR, Habtamu E, Mwangi N, Silva JC, Swenor BK, Congdon N, Faal HB, Foster A, Friedman DS, Gichuhi S, Jonas JB, Khaw PT, Kyari F, Murthy GVS, Wang N, Wong TY, Wormald R, Yusufu M, Taylor H, Resnikoff S, West SK, Burton MJ, in study group GCGEH. Grand Challenges in global eye health: a global prioritisation process using Delphi method. Lancet Healthy Longev 2022;3(1):e31-e41.Abstract
Background: We undertook a Grand Challenges in Global Eye Health prioritisation exercise to identify the key issues that must be addressed to improve eye health in the context of an ageing population, to eliminate persistent inequities in health-care access, and to mitigate widespread resource limitations. Methods: Drawing on methods used in previous Grand Challenges studies, we used a multi-step recruitment strategy to assemble a diverse panel of individuals from a range of disciplines relevant to global eye health from all regions globally to participate in a three-round, online, Delphi-like, prioritisation process to nominate and rank challenges in global eye health. Through this process, we developed both global and regional priority lists. Findings: Between Sept 1 and Dec 12, 2019, 470 individuals complete round 1 of the process, of whom 336 completed all three rounds (round 2 between Feb 26 and March 18, 2020, and round 3 between April 2 and April 25, 2020) 156 (46%) of 336 were women, 180 (54%) were men. The proportion of participants who worked in each region ranged from 104 (31%) in sub-Saharan Africa to 21 (6%) in central Europe, eastern Europe, and in central Asia. Of 85 unique challenges identified after round 1, 16 challenges were prioritised at the global level; six focused on detection and treatment of conditions (cataract, refractive error, glaucoma, diabetic retinopathy, services for children and screening for early detection), two focused on addressing shortages in human resource capacity, five on other health service and policy factors (including strengthening policies, integration, health information systems, and budget allocation), and three on improving access to care and promoting equity. Interpretation: This list of Grand Challenges serves as a starting point for immediate action by funders to guide investment in research and innovation in eye health. It challenges researchers, clinicians, and policy makers to build collaborations to address specific challenges. Funding: The Queen Elizabeth Diamond Jubilee Trust, Moorfields Eye Charity, National Institute for Health Research Moorfields Biomedical Research Centre, Wellcome Trust, Sightsavers, The Fred Hollows Foundation, The Seva Foundation, British Council for the Prevention of Blindness, and Christian Blind Mission. Translations: For the French, Spanish, Chinese, Portuguese, Arabic and Persian translations of the abstract see Supplementary Materials section.
Nwanaji-Enwerem JC, Gateman T, Whitecross S, Whitman MC. First Visit Characteristics Associated with Future Surgery in Intermittent Exotropia. J Binocul Vis Ocul Motil 2022;:1-7.Abstract
PURPOSE: Identify demographic and clinical characteristics at the first presentation associated with later having surgery for intermittent exotropia (IXT). METHODS: Retrospective cohort study of 228 children with IXT and 5+ years of follow-up. Demographic and clinical data were extracted from medical records. A total 97 participants who underwent surgery during follow-up were compared to 131 participants who did not. Best subset regression was used to identify first visit variables associated with later having strabismus surgery. Surgery was then regressed on the selected variables using logistic models. RESULTS: Age and control were the only first visit variables significantly associated with having surgery for IXT. Notably, neither angle of deviation nor stereopsis were associated with later surgery. In an adjusted logistic model, each one-month increase in age at presentation was associated with a 1% decrease in the odds of having surgery (OR = 0.991, 95% CI: 0.982-0.999, P = .04). Children with poor control at initial visit had almost five times greater odds of having surgery than those with good control (OR = 4.95, 95% CI: 2.31-10.98, P < .0001). CONCLUSIONS: Age and control of IXT are important factors at presentation associated with future surgical intervention for IXT. The magnitude of deviation and stereopsis was not significantly associated with future surgical treatment for IXT.
Liou VD, Yoon MK, Maher M, Chwalisz BK. Orbital Inflammation in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: A Case Report and Review of the Literature. J Neuroophthalmol 2022;Abstract
BACKGROUND: To present 2 patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease with unilateral orbital inflammation, optic nerve head edema, and abnormalities of the optic nerve and nerve sheath on imaging. We review the most current literature on this important and uncommon clinical phenotype. METHODS: A case report of 2 patients and a comprehensive review of the relevant literature on orbital inflammation in MOG antibody-associated disease (MOG-AD). RESULTS: Two patients presented with decreased vision and unilateral orbital inflammation. Both had optic nerve head edema and abnormalities of the optic nerve and nerve sheath on imaging. The patients were treated with immunosuppressants and had improvement of vision changes as well as their orbital inflammatory signs. MOG antibody was positive in high titers in both patients. Only 3 other cases of orbital inflammation associated with MOG antibody have been described. In all cases, orbital signs responded rapidly to intravenous methylprednisolone, but the improvement in visual acuity was variable and less robust. CONCLUSION: Orbital inflammation is a unique and underrecognized phenotype of MOG-AD with only a few reports in the literature. In patients who present with vision loss and orbital inflammation, MOG-AD should be considered in the differential.
Aboobakar IF, Wiggs JL. The genetics of glaucoma: Disease associations, personalised risk assessment and therapeutic opportunities-A review. Clin Exp Ophthalmol 2022;50(2):143-162.Abstract
Glaucoma refers to a heterogenous group of disorders characterised by progressive loss of retinal ganglion cells and associated visual field loss. Both early-onset and adult-onset forms of the disease have a strong genetic component. Here, we summarise the known genetic associations for various forms of glaucoma and the possible functional roles for these genes in disease pathogenesis. We also discuss efforts to translate genetic knowledge into clinical practice, including gene-based tests for disease diagnosis and risk-stratification as well as gene-based therapies.
Lin JB, Halawa OA, Husain D, Miller JW, Vavvas DG. Dyslipidemia in age-related macular degeneration. Eye (Lond) 2022;36(2):312-318.Abstract
Lipid-rich drusen are the sine qua non of age-related macular degeneration (AMD), the leading cause of blindness in older adults in the developed world. Efforts directed at uncovering effective therapeutic strategies have led to the hypothesis that altered lipid metabolism may play a pathogenic role in AMD. This hypothesis is supported by the fact that: (1) drusen, the hallmark histopathologic feature of AMD, are composed of lipids, (2) polymorphisms of genes involved in lipid homeostasis are associated with increased odds of AMD, (3) metabolomics studies show that patients with AMD have alterations in metabolites from lipid pathways, and (4) alterations in serum lipid profiles as a reflection of systemic dyslipidemia are associated with AMD. There is strong evidence that statins, which are well described for treating dyslipidemia and reducing risk associated with cardiovascular disease, may have a role for treating certain cohorts of AMD patients, but this has yet to be conclusively proven. Of interest, the specific changes in serum lipoprotein profiles associated with decreased cardiovascular risk (i.e., high HDL levels) have been shown in some studies to be associated with increased risk of AMD. In this review, we highlight the evidence that supports a role for altered lipid metabolism in AMD and provide our perspective regarding the remaining questions that need to be addressed before lipid-based therapies can emerge for specific cohorts of AMD patients.