Medicine › Ophthalmology

Retinal Diseases and Treatments

Works Count: 79451

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Description

This cluster of papers focuses on research related to age-related macular degeneration (AMD) and diabetic retinopathy. It covers topics such as the role of oxidative stress, vascular endothelial growth factor, complement factor H polymorphism, and choroidal thickness in the pathogenesis and treatment of these diseases. Additionally, it explores the use of intravitreal injections and optical coherence tomography angiography in understanding and managing AMD and diabetic retinopathy.

Keywords

Macular Degeneration; Retinal Pigment Epithelium; Diabetic Retinopathy; Oxidative Stress; Vascular Endothelial Growth Factor; Choroidal Thickness; Intravitreal Injection; Complement Factor H Polymorphism; Optical Coherence Tomography Angiography; Inflammation

Ranibizumab and Bevacizumab for Neovascular Age-Related Macular Degeneration

2011-04-28

Daniel F Martin , Maureen G. Maguire , Gui‐Shuang Ying +3 more

Clinical trials have established the efficacy of ranibizumab for the treatment of neovascular age-related macular degeneration (AMD). In addition, bevacizumab is used off-label to treat AMD, despite the absence of … Clinical trials have established the efficacy of ranibizumab for the treatment of neovascular age-related macular degeneration (AMD). In addition, bevacizumab is used off-label to treat AMD, despite the absence of similar supporting data.In a multicenter, single-blind, noninferiority trial, we randomly assigned 1208 patients with neovascular AMD to receive intravitreal injections of ranibizumab or bevacizumab on either a monthly schedule or as needed with monthly evaluation. The primary outcome was the mean change in visual acuity at 1 year, with a noninferiority limit of 5 letters on the eye chart.Bevacizumab administered monthly was equivalent to ranibizumab administered monthly, with 8.0 and 8.5 letters gained, respectively. Bevacizumab administered as needed was equivalent to ranibizumab as needed, with 5.9 and 6.8 letters gained, respectively. Ranibizumab as needed was equivalent to monthly ranibizumab, although the comparison between bevacizumab as needed and monthly bevacizumab was inconclusive. The mean decrease in central retinal thickness was greater in the ranibizumab-monthly group (196 μm) than in the other groups (152 to 168 μm, P=0.03 by analysis of variance). Rates of death, myocardial infarction, and stroke were similar for patients receiving either bevacizumab or ranibizumab (P>0.20). The proportion of patients with serious systemic adverse events (primarily hospitalizations) was higher with bevacizumab than with ranibizumab (24.1% vs. 19.0%; risk ratio, 1.29; 95% confidence interval, 1.01 to 1.66), with excess events broadly distributed in disease categories not identified in previous studies as areas of concern.At 1 year, bevacizumab and ranibizumab had equivalent effects on visual acuity when administered according to the same schedule. Ranibizumab given as needed with monthly evaluation had effects on vision that were equivalent to those of ranibizumab administered monthly. Differences in rates of serious adverse events require further study. (Funded by the National Eye Institute; ClinicalTrials.gov number, NCT00593450.).

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Prevalence of Age-Related Macular Degeneration in the United States

2004-04-01

David S. Friedman , Benita J O'Colmain , Beatriz Muñoz +6 more

<h3>Objective</h3> To estimate the prevalence and distribution of age-related macular degeneration(AMD) in the United States by age, race/ethnicity, and gender. <h3>Methods</h3> Summary prevalence estimates of drusen 125 µm or larger, … <h3>Objective</h3> To estimate the prevalence and distribution of age-related macular degeneration(AMD) in the United States by age, race/ethnicity, and gender. <h3>Methods</h3> Summary prevalence estimates of drusen 125 µm or larger, neovascularAMD, and geographic atrophy were prepared separately for black and white personsin 5-year age intervals starting at 40 years. The estimated rates were basedon a meta-analysis of recent population-based studies in the United States,Australia, and Europe. These rates were applied to 2000 US Census data andto projected US population figures for 2020 to estimate the number of theUS population with drusen and AMD. <h3>Results</h3> The overall prevalence of neovascular AMD and/or geographic atrophyin the US population 40 years and older is estimated to be 1.47% (95% confidenceinterval, 1.38%-1.55%), with 1.75 million citizens having AMD. The prevalenceof AMD increased dramatically with age, with more than 15% of the white womenolder than 80 years having neovascular AMD and/or geographic atrophy. Morethan 7 million individuals had drusen measuring 125 µm or larger andwere, therefore, at substantial risk of developing AMD. Owing to the rapidlyaging population, the number of persons having AMD will increase by 50% to2.95 million in 2020. Age-related macular degeneration was far more prevalentamong white than among black persons. <h3>Conclusion</h3> Age-related macular degeneration affects more than 1.75 million individualsin the United States. Owing to the rapid aging of the US population, thisnumber will increase to almost 3 million by 2020.

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Ranibizumab and Bevacizumab for Treatment of Neovascular Age-related Macular Degeneration

2012-05-01

Daniel Martín , Maureen G. Maguire , Stuart L. Fine +6 more

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Photodynamic Therapy of Subfoveal Choroidal Neovascularization in Age-related Macular Degeneration With Verteporfin

1999-10-01

Neil M. Bressler

<h3>Objective</h3> To determine if photodynamic therapy with verteporfin (Visudyne; CIBA Vision Corp, Duluth, Ga) can safely reduce the risk of vision loss in patients with subfoveal choroidal neovascularization (CNV) caused … <h3>Objective</h3> To determine if photodynamic therapy with verteporfin (Visudyne; CIBA Vision Corp, Duluth, Ga) can safely reduce the risk of vision loss in patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration (AMD). <h3>Design</h3> Two multicenter, double-masked, placebo-controlled, randomized clinical trials. <h3>Setting</h3> Twenty-two ophthalmology practices in Europe and North America. <h3>Participants</h3> Patients with subfoveal CNV lesions caused by AMD measuring 5400 µm or less in greatest linear dimension with evidence of classic CNV and best-corrected visual acuity of approximately 20/40 to 20/200. <h3>Methods</h3> Six hundred nine patients were randomly assigned (2:1) to verteporfin (6 mg per square meter of body surface area) or placebo (5% dextrose in water) administered via intravenous infusion of 30 mL over 10 minutes. Fifteen minutes after the start of the infusion, a laser light at 689 nm delivered 50 J/cm<sup>2</sup>at an intensity of 600 mW/cm<sup>2</sup>over 83 seconds using a spot size with a diameter 1000 µm larger than the greatest linear dimension of the CNV lesion. At follow-up examinations every 3 months, retreatment with the same regimen was applied if angiography showed fluorescein leakage. The primary outcome was the proportion of eyes with fewer than 15 letters lost (approximately <3 lines of loss), adhering to an intent-to-treat analysis. <h3>Results</h3> In each group, 94% of patients completed the month 12 examination. Visual acuity, contrast sensitivity, and fluorescein angiographic outcomes were better in the verteporfin-treated eyes than in the placebo-treated eyes at every follow-up examination through the month 12 examination. At the month-12 examination, 246 (61%) of 402 eyes assigned to verteporfin compared with 96 (46%) of 207 eyes assigned to placebo had lost fewer than 15 letters of visual acuity from baseline (<i>P</i><.001). In subgroup analyses, the visual acuity benefit (<15 letters lost) of verteporfin therapy was clearly demonstrated (67% vs 39%;<i>P</i><.001) when the area of classic CNV occupied 50% or more of the area of the entire lesion (termed<i>predominantly classic CNV lesions</i>), especially when there was no occult CNV. No statistically significant differences in visual acuity were noted when the area of classic CNV was more than 0% but less than 50% of the area of the entire lesion. Few ocular or other systemic adverse events were associated with verteporfin treatment, compared with placebo, including transient visual disturbances (18% vs 12%), injection-site adverse events (13% vs 3%), transient photosensitivity reactions (3% vs 0%), and infusion-related low back pain (2% vs 0%). <h3>Conclusions</h3> Since verteporfin therapy of subfoveal CNV from AMD can safely reduce the risk of vision loss, we recommend verteporfin therapy for treatment of patients with predominantly classic CNV from AMD.

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Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema

2015-02-18

John A. Wells , Adam R. Glassman , Allison R. Ayala +7 more

The relative efficacy and safety of intravitreous aflibercept, bevacizumab, and ranibizumab in the treatment of diabetic macular edema are unknown. The relative efficacy and safety of intravitreous aflibercept, bevacizumab, and ranibizumab in the treatment of diabetic macular edema are unknown.

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Pegaptanib for Neovascular Age-Related Macular Degeneration

2004-12-30

Evangelos S. Gragoudas , Anthony P. Adamis , Emmett T. Cunningham +2 more

Pegaptanib, an anti–vascular endothelial growth factor therapy, was evaluated in the treatment of neovascular age-related macular degeneration. Pegaptanib, an anti–vascular endothelial growth factor therapy, was evaluated in the treatment of neovascular age-related macular degeneration.

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Prevalence of Age-related Maculopathy

1992-06-01

Ronald Klein , Kathryn L.P. Linton

Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss

2015-09-29

Ryan Lee , Tien Yin Wong , Charumathi Sabanayagam

Diabetic retinopathy (DR) is a leading cause of vision-loss globally. Of an estimated 285 million people with diabetes mellitus worldwide, approximately one third have signs of DR and of these, … Diabetic retinopathy (DR) is a leading cause of vision-loss globally. Of an estimated 285 million people with diabetes mellitus worldwide, approximately one third have signs of DR and of these, a further one third of DR is vision-threatening DR, including diabetic macular edema (DME). The identification of established modifiable risk factors for DR such as hyperglycemia and hypertension has provided the basis for risk factor control in preventing onset and progression of DR. Additional research investigating novel risk factors has improved our understanding of multiple biological pathways involved in the pathogenesis of DR and DME, especially those involved in inflammation and oxidative stress. Variations in DR prevalence between populations have also sparked interest in genetic studies to identify loci associated with disease susceptibility. In this review, major trends in the prevalence, incidence, progression and regression of DR and DME are explored, and gaps in literature identified. Established and novel risk factors are also extensively reviewed with a focus on landmark studies and updates from the recent literature.

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Onset of NIDDM occurs at Least 4–7 yr Before Clinical Diagnosis

1992-07-01

Maureen I Harris , Ronald Klein , T. A. Welborn +1 more

Objective To investigate duration of the period between diabetes onset and its clinical diagnosis. Research Design and Methods Two population-based groups of white patients with non-insulin-dependent diabetes (NIDDM) in the … Objective To investigate duration of the period between diabetes onset and its clinical diagnosis. Research Design and Methods Two population-based groups of white patients with non-insulin-dependent diabetes (NIDDM) in the United States and Australia were studied. Prevalence of retinopathy and duration of diabetes subsequent to clinical diagnosis were determined for all subjects. Weighted linear regression was used to examine the relationship between diabetes duration and prevalence of retinopathy. Results Prevalence of retinopathy at clinical diagnosis of diabetes was estimated to be 20.8% in the U.S. and 9.9% in Australia and increased linearly with longer duration of diabetes. By extrapolating this linear relationship to the time when retinopathy prevalence was estimated to be zero, onset of detectable retinopathy was calculated to have occurred ∼ 4–7 yr before diagnosis of NIDDM. Because other data indicate that diabetes may be present for 5 yr before retinopathy becomes evident, onset of NIDDM may occur 9–12 yr before its clinical diagnosis. Conclusions These findings suggest that undiagnosed NIDDM is not a benign condition. Clinically significant morbidity is present at diagnosis and for years before diagnosis. During this preclinical period, treatment is not being offered for diabetes or its specific complications, despite the fact that reduction in hyperglycemia, hypertension, and cardiovascular risk factors is believed to benefit patients. Imprecise dating of diabetes onset also obscures investigations of the etiology of NIDDM and studies of the nature and importance of risk factors for diabetes complications.

Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales

2003-09-01

C. P. Wilkinson , Frederick L. Ferris , Ronald Klein +7 more

Clinical Classification of Age-related Macular Degeneration

2013-01-16

Frederick L. Ferris , Charles P. Wilkinson , Alan C. Bird +4 more

Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin.

1998-08-15

Alistair J. Barber , Erich Lieth , Sonny Khin +3 more

This study determined whether retinal degeneration during diabetes includes retinal neural cell apoptosis. Image analysis of retinal sections from streptozotocin (STZ) diabetic rats after 7.5 months of STZ diabetes identified … This study determined whether retinal degeneration during diabetes includes retinal neural cell apoptosis. Image analysis of retinal sections from streptozotocin (STZ) diabetic rats after 7.5 months of STZ diabetes identified 22% and 14% reductions in the thickness of the inner plexiform and inner nuclear layers, respectively (P < 0. 001). The number of surviving ganglion cells was also reduced by 10% compared to controls (P < 0.001). In situ end labeling of DNA terminal dUTP nick end labeling (TUNEL) identified a 10-fold increase in the frequency of retinal apoptosis in whole-mounted rat retinas after 1, 3, 6, and 12 months of diabetes (P < 0.001, P < 0. 001, P < 0.01, and P < 0.01, respectively). Most TUNEL-positive cells were not associated with blood vessels and did not colocalize with the endothelial cell-specific antigen, von Willebrand factor. Insulin implants significantly reduced the number of TUNEL-positive cells (P < 0.05). The number of TUNEL-positive cells was also increased in retinas from humans with diabetes. These data indicate that retinal neural cell death occurs early in diabetes. This is the first quantitative report of an increase in neural cell apoptosis in the retina during diabetes, and indicates that neurodegeneration is an important component of diabetic retinopathy.

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An Integrated Hypothesis That Considers Drusen as Biomarkers of Immune-Mediated Processes at the RPE-Bruch's Membrane Interface in Aging and Age-Related Macular Degeneration

2001-11-01

Gregory S. Hageman , Philip J. Luthert , Victor Chong +3 more

Intravitreal Aflibercept (VEGF Trap-Eye) in Wet Age-related Macular Degeneration

2012-10-17

Jeffrey S. Heier , David M. Brown , Victor Chong +7 more

The Wisconsin Epidemiologic Study of Diabetic Retinopathy

1984-04-01

Ronald Klein

• In a population-based study in southern Wisconsin, 1,370 patients given diagnoses of diabetes at age 30 years or older were examined using standard protocols to determine the prevalence and … • In a population-based study in southern Wisconsin, 1,370 patients given diagnoses of diabetes at age 30 years or older were examined using standard protocols to determine the prevalence and severity of diabetic retinopathy and associated risk variables. The prevalence of diabetic retinopathy varied from 28.8% in persons who had diabetes for less than five years to 77.8% in persons who had diabetes for 15 or more years. The rate of proliferative diabetic retinopathy varied from 2.0% in persons who had diabetes for less than five years to 15.5% in persons who had diabetes for 15 or more years. By using the Cox regression model, the severity of retinopathy was found to be related to longer duration of diabetes, younger age at diagnosis, higher glycosylated hemoglobin levels, higher systolic BP, use of insulin, presence of proteinuria, and small body mass.

Pigment Epithelium-Derived Factor: A Potent Inhibitor of Angiogenesis

1999-07-09

David W. Dawson , Olga V. Volpert , Paul Gillis +4 more

In the absence of disease, the vasculature of the mammalian eye is quiescent, in part because of the action of angiogenic inhibitors that prevent vessels from invading the cornea and … In the absence of disease, the vasculature of the mammalian eye is quiescent, in part because of the action of angiogenic inhibitors that prevent vessels from invading the cornea and vitreous. Here, an inhibitor responsible for the avascularity of these ocular compartments is identified as pigment epithelium–derived factor (PEDF), a protein previously shown to have neurotrophic activity. The amount of inhibitory PEDF produced by retinal cells was positively correlated with oxygen concentrations, suggesting that its loss plays a permissive role in ischemia-driven retinal neovascularization. These results suggest that PEDF may be of therapeutic use, especially in retinopathies where pathological neovascularization compromises vision and leads to blindness.

Randomized Trial Evaluating Ranibizumab Plus Prompt or Deferred Laser or Triamcinolone Plus Prompt Laser for Diabetic Macular Edema

2010-04-29

Michael J. Elman , Lloyd Paul Aiello , Roy W. Beck +7 more

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The Wisconsin Epidemiologic Study of Diabetic Retinopathy

1984-04-01

Ronald Klein

• In a population-based study in southern Wisconsin, 996 insulin-taking, younger-onset diabetic persons were examined using standard protocols to determine the prevalence and severity of diabetic retinopathy and associated risk … • In a population-based study in southern Wisconsin, 996 insulin-taking, younger-onset diabetic persons were examined using standard protocols to determine the prevalence and severity of diabetic retinopathy and associated risk variables. The prevalence of diabetic retinopathy varied from 17% to 97.5% in persons with diabetes for less than five years and 15 or more years, respectively. Proliferative retinopathy varied from 1.2% to 67% in persons with diabetes for less than ten years and 35 or more years, respectively. For persons with diabetes of 10 years' duration or less, the Cox regression model relates the severity of retinopathy to longer duration, older age at examination, and higher levels of glycosylated hemoglobin. After ten years of diabetes, severity of retinopathy was related to longer duration, high levels of glycosylated hemoglobin, presence of proteinuria. higher diastolic BP, and male sex.

Ranibizumab versus Verteporfin Photodynamic Therapy for Neovascular Age-Related Macular Degeneration: Two-Year Results of the ANCHOR Study

2008-12-31

David M. Brown , Mark Michels , Peter K. Kaiser +3 more

An international classification and grading system for age-related maculopathy and age-related macular degeneration

1995-03-01

Alan C. Bird , Neil M. Bressler , Susan B. Bressler +7 more

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Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins.

1995-11-07

Lloyd Paul Aiello , Eric A. Pierce , E D Foley +6 more

The majority of severe visual loss in the United States results from complications associated with retinal neovascularization in patients with ischemic ocular diseases such as diabetic retinopathy, retinal vein occlusion, … The majority of severe visual loss in the United States results from complications associated with retinal neovascularization in patients with ischemic ocular diseases such as diabetic retinopathy, retinal vein occlusion, and retinopathy of prematurity. Intraocular expression of the angiogenic protein vascular endothelial growth factor (VEGF) is closely correlated with neovascularization in these human disorders and with ischemia-induced retinal neovascularization in mice. In this study, we evaluated whether in vivo inhibition of VEGF action could suppress retinal neovascularization in a murine model of ischemic retinopathy. VEGF-neutralizing chimeric proteins were constructed by joining the extracellular domain of either human (Flt) or mouse (Flk) high-affinity VEGF receptors with IgG. Control chimeric proteins that did not bind VEGF were also used. VEGF-receptor chimeric proteins eliminated in vitro retinal endothelial cell growth stimulation by either VEGF (P < 0.006) or hypoxic conditioned medium (P < 0.005) without affecting growth under nonstimulated conditions. Control proteins had no effect. To assess in vivo response, animals with bilateral retinal ischemia received intravitreal injections of VEGF antagonist in one eye and control protein in the contralateral eye. Retinal neovascularization was quantitated histologically by a masked protocol. Retinal neovascularization in the eye injected with human Flt or murine Flk chimeric protein was reduced in 100% (25/25; P < 0.0001) and 95% (21/22; P < 0.0001) 0.0001) of animals, respectively, compared to the control treated eye. This response was evident after only a single intravitreal injection and was dose dependent with suppression of neovascularization noted after total delivery of 200 ng of protein (P < 0.002). Reduction of histologically evident neovascular nuclei per 6-microns section averaged 47% +/- 4% (P < 0.001) and 37% +/- 2% (P < 0.001) for Flt and Flk chimeric proteins with maximal inhibitory effects of 77% and 66%, respectively. No retinal toxicity was observed by light microscopy. These data demonstrate VEGF's causal role in retinal angiogenesis and prove the potential of VEGF inhibition as a specific therapy for ischemic retinal disease.

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Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study

1995-05-01

Yasuo Ohkubo , Hideki Kishikawa , Eiichi Araki +6 more

Ranibizumab versus Verteporfin for Neovascular Age-Related Macular Degeneration

2006-10-04

David M. Brown , Peter K. Kaiser , Mark Michels +5 more

We compared ranibizumab — a recombinant, humanized, monoclonal antibody Fab that neutralizes all active forms of vascular endothelial growth factor A — with photodynamic therapy with verteporfin in the treatment … We compared ranibizumab — a recombinant, humanized, monoclonal antibody Fab that neutralizes all active forms of vascular endothelial growth factor A — with photodynamic therapy with verteporfin in the treatment of predominantly classic neovascular age-related macular degeneration.

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Complement Factor H Polymorphism in Age-Related Macular Degeneration

2005-03-11

Robert J. Klein , Caroline J. Zeiss , Emily Y. Chew +7 more

Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. We report a genome-wide screen of 96 cases and 50 controls for polymorphisms associated with AMD. Among … Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. We report a genome-wide screen of 96 cases and 50 controls for polymorphisms associated with AMD. Among 116,204 single-nucleotide polymorphisms genotyped, an intronic and common variant in the complement factor H gene ( CFH ) is strongly associated with AMD (nominal P value <10 -7 ). In individuals homozygous for the risk allele, the likelihood of AMD is increased by a factor of 7.4 (95% confidence interval 2.9 to 19). Resequencing revealed a polymorphism in linkage disequilibrium with the risk allele representing a tyrosine-histidine change at amino acid 402. This polymorphism is in a region of CFH that binds heparin and C-reactive protein. The CFH gene is located on chromosome 1 in a region repeatedly linked to AMD in family-based studies.

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Complement Factor H Variant Increases the Risk of Age-Related Macular Degeneration

2005-03-11

Jonathan L. Haines , Michael A. Hauser , Silke Schmidt +7 more

Age-related macular degeneration (AMD) is a leading cause of visual impairment and blindness in the elderly whose etiology remains largely unknown. Previous studies identified chromosome 1q32 as harboring a susceptibility … Age-related macular degeneration (AMD) is a leading cause of visual impairment and blindness in the elderly whose etiology remains largely unknown. Previous studies identified chromosome 1q32 as harboring a susceptibility locus for AMD. We used single-nucleotide polymorphisms to interrogate this region and identified a strongly associated haplotype in two independent data sets. DNA resequencing of the complement factor H gene within this haplotype revealed a common coding variant, Y402H, that significantly increases the risk for AMD with odds ratios between 2.45 and 5.57. This common variant likely explains ∼43% of AMD in older adults.

The Wisconsin Epidemiologic Study of Diabetic Retinopathy

1987-07-01

Ronald Klein , Scot E. Moss , Matthew D. Davis +1 more

Ranibizumab for Neovascular Age-Related Macular Degeneration

2006-10-04

Philip J. Rosenfeld , David M. Brown , Jeffrey S. Heier +4 more

Ranibizumab--a recombinant, humanized, monoclonal antibody Fab that neutralizes all active forms of vascular endothelial growth factor A--has been evaluated for the treatment of neovascular age-related macular degeneration.In this multicenter, 2-year, … Ranibizumab--a recombinant, humanized, monoclonal antibody Fab that neutralizes all active forms of vascular endothelial growth factor A--has been evaluated for the treatment of neovascular age-related macular degeneration.In this multicenter, 2-year, double-blind, sham-controlled study, we randomly assigned patients with age-related macular degeneration with either minimally classic or occult (with no classic lesions) choroidal neovascularization to receive 24 monthly intravitreal injections of ranibizumab (either 0.3 mg or 0.5 mg) or sham injections. The primary end point was the proportion of patients losing fewer than 15 letters from baseline visual acuity at 12 months.We enrolled 716 patients in the study. At 12 months, 94.5% of the group given 0.3 mg of ranibizumab and 94.6% of those given 0.5 mg lost fewer than 15 letters, as compared with 62.2% of patients receiving sham injections (P<0.001 for both comparisons). Visual acuity improved by 15 or more letters in 24.8% of the 0.3-mg group and 33.8% of the 0.5-mg group, as compared with 5.0% of the sham-injection group (P<0.001 for both doses). Mean increases in visual acuity were 6.5 letters in the 0.3-mg group and 7.2 letters in the 0.5-mg group, as compared with a decrease of 10.4 letters in the sham-injection group (P<0.001 for both comparisons). The benefit in visual acuity was maintained at 24 months. During 24 months, presumed endophthalmitis was identified in five patients (1.0%) and serious uveitis in six patients (1.3%) given ranibizumab.Intravitreal administration of ranibizumab for 2 years prevented vision loss and improved mean visual acuity, with low rates of serious adverse events, in patients with minimally classic or occult (with no classic lesions) choroidal neovascularization secondary to age-related macular degeneration. (ClinicalTrials.gov number, NCT00056836 [ClinicalTrials.gov].).

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A common haplotype in the complement regulatory gene factor H ( <i>HF1/CFH</i> ) predisposes individuals to age-related macular degeneration

2005-05-03

Gregory S. Hageman , Don H. Anderson , Lincoln V. Johnson +7 more

Age-related macular degeneration (AMD) is the most frequent cause of irreversible blindness in the elderly in developed countries. Our previous studies implicated activation of complement in the formation of drusen, … Age-related macular degeneration (AMD) is the most frequent cause of irreversible blindness in the elderly in developed countries. Our previous studies implicated activation of complement in the formation of drusen, the hallmark lesion of AMD. Here, we show that factor H (HF1), the major inhibitor of the alternative complement pathway, accumulates within drusen and is synthesized by the retinal pigmented epithelium. Because previous linkage analyses identified chromosome 1q25-32, which harbors the factor H gene ( HF1 / CFH ), as an AMD susceptibility locus, we analyzed HF1 for genetic variation in two independent cohorts comprised of ≈900 AMD cases and 400 matched controls. We found association of eight common HF1 SNPs with AMD; two common missense variants exhibit highly significant associations (I62V, χ 2 = 26.1 and P = 3.2 × 10 -7 and Y402H, χ 2 = 54.4 and P = 1.6 × 10 -13 ). Haplotype analysis reveals that multiple HF1 variants confer elevated or reduced risk of AMD. One common at-risk haplotype is present at a frequency of 50% in AMD cases and 29% in controls [odds ratio (OR) = 2.46, 95% confidence interval (1.95-3.11)]. Homozygotes for this haplotype account for 24% of cases and 8% of controls [OR = 3.51, 95% confidence interval (2.13-5.78)]. Several protective haplotypes are also identified (OR = 0.44-0.55), further implicating HF1 function in the pathogenetic mechanisms underlying AMD. We propose that genetic variation in a regulator of the alternative complement pathway, when combined with a triggering event, such as infection, underlie a major proportion of AMD in the human population.

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Microvascular and Macrovascular Complications of Diabetes

2008-04-01

Michael J. Fowler

Diabetes is a group of chronic diseases characterized by hyperglycemia. Modern medical care uses a vast array of lifestyle and pharmaceutical interventions aimed at preventing and controlling hyperglycemia. In addition … Diabetes is a group of chronic diseases characterized by hyperglycemia. Modern medical care uses a vast array of lifestyle and pharmaceutical interventions aimed at preventing and controlling hyperglycemia. In addition to ensuring the adequate delivery of glucose to the tissues of the body, treatment of diabetes attempts to decrease the likelihood that the tissues of the body are harmed by hyperglycemia. The importance of protecting the body from hyperglycemia cannot be overstated; the direct and indirect effects on the human vascular tree are the major source of morbidity and mortality in both type 1 and type 2 diabetes. Generally, the injurious effects of hyperglycemia are separated into macrovascular complications (coronary artery disease, peripheral arterial disease, and stroke) and microvascular complications (diabetic nephropathy, neuropathy, and retinopathy). It is important for physicians to understand the relationship between diabetes and vascular disease because the prevalence of diabetes continues to increase in the United States, and the clinical armamentarium for primary and secondary prevention of these complications is also expanding. ### Diabetic retinopathy Diabetic retinopathy may be the most common microvascular complication of diabetes. It is responsible for ∼ 10,000 new cases of blindness every year in the United States alone.1 The risk of developing diabetic retinopathy or other microvascular complications of diabetes depends on both the duration and the severity of hyperglycemia. Development of diabetic retinopathy in patients with type 2 diabetes was found to be related to both severity of hyperglycemia and presence of hypertension in the U.K. Prospective Diabetes Study (UKPDS), and most patients with type 1 diabetes develop evidence of retinopathy within 20 years of diagnosis.2,3 Retinopathy may begin to develop as early as 7 years before the diagnosis of diabetes in patients with type 2 diabetes.1 There are several proposed pathological mechanisms by which diabetes may lead …

Increased Vascular Endothelial Growth Factor Levels in the Vitreous of Eyes With Proliferative Diabetic Retinopathy

1994-10-01

A.P. Adamis , Joan W. Miller , Teresa Bernal +4 more

Global Prevalence and Major Risk Factors of Diabetic Retinopathy

2012-02-02

Joanne Yau , Sophie Rogers , Ryo Kawasaki +7 more

To examine the global prevalence and major risk factors for diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) among people with diabetes.A pooled analysis using individual participant data from population-based … To examine the global prevalence and major risk factors for diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) among people with diabetes.A pooled analysis using individual participant data from population-based studies around the world was performed. A systematic literature review was conducted to identify all population-based studies in general populations or individuals with diabetes who had ascertained DR from retinal photographs. Studies provided data for DR end points, including any DR, proliferative DR, diabetic macular edema, and VTDR, and also major systemic risk factors. Pooled prevalence estimates were directly age-standardized to the 2010 World Diabetes Population aged 20-79 years.A total of 35 studies (1980-2008) provided data from 22,896 individuals with diabetes. The overall prevalence was 34.6% (95% CI 34.5-34.8) for any DR, 6.96% (6.87-7.04) for proliferative DR, 6.81% (6.74-6.89) for diabetic macular edema, and 10.2% (10.1-10.3) for VTDR. All DR prevalence end points increased with diabetes duration, hemoglobin A(1c), and blood pressure levels and were higher in people with type 1 compared with type 2 diabetes.There are approximately 93 million people with DR, 17 million with proliferative DR, 21 million with diabetic macular edema, and 28 million with VTDR worldwide. Longer diabetes duration and poorer glycemic and blood pressure control are strongly associated with DR. These data highlight the substantial worldwide public health burden of DR and the importance of modifiable risk factors in its occurrence. This study is limited by data pooled from studies at different time points, with different methodologies and population characteristics.

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The Role of Oxidative Stress in the Pathogenesis of Age-Related Macular Degeneration

2000-09-01

Stephen Beatty , Hui-Hiang Koh , M. Phil +2 more

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The RESTORE Study

2011-04-01

Paul Mitchell , Francesco Bandello , Ursula Schmidt‐Erfurth +7 more

ObjectiveTo demonstrate superiority of ranibizumab 0.5 mg monotherapy or combined with laser over laser alone based on mean average change in best-corrected visual acuity (BCVA) over 12 months in diabetic … ObjectiveTo demonstrate superiority of ranibizumab 0.5 mg monotherapy or combined with laser over laser alone based on mean average change in best-corrected visual acuity (BCVA) over 12 months in diabetic macular edema (DME).DesignA 12-month, randomized, double-masked, multicenter, laser-controlled phase III study.ParticipantsWe included 345 patients aged ≥18 years, with type 1 or 2 diabetes mellitus and visual impairment due to DME.MethodsPatients were randomized to ranibizumab + sham laser (n = 116), ranibizumab + laser (n = 118), or sham injections + laser (n = 111). Ranibizumab/sham was given for 3 months then pro re nata (PRN); laser/sham laser was given at baseline then PRN (patients had scheduled monthly visits).Main Outcome MeasuresMean average change in BCVA from baseline to month 1 through 12 and safety.ResultsRanibizumab alone and combined with laser were superior to laser monotherapy in improving mean average change in BCVA letter score from baseline to month 1 through 12 (+6.1 and +5.9 vs +0.8; both P<0.0001). At month 12, a significantly greater proportion of patients had a BCVA letter score ≥15 and BCVA letter score level >73 (20/40 Snellen equivalent) with ranibizumab (22.6% and 53%, respectively) and ranibizumab + laser (22.9% and 44.9%) versus laser (8.2% and 23.6%). The mean central retinal thickness was significantly reduced from baseline with ranibizumab (−118.7 μm) and ranibizumab + laser (−128.3 μm) versus laser (−61.3 μm; both P<0.001). Health-related quality of life, assessed through National Eye Institute Visual Function Questionnaire (NEI VFQ-25), improved significantly from baseline with ranibizumab alone and combined with laser (P<0.05 for composite score and vision-related subscales) versus laser. Patients received ∼7 (mean) ranibizumab/sham injections over 12 months. No endophthalmitis cases occurred. Increased intraocular pressure was reported for 1 patient each in the ranibizumab arms. Ranibizumab monotherapy or combined with laser was not associated with an increased risk of cardiovascular or cerebrovascular events in this study.ConclusionsRanibizumab monotherapy and combined with laser provided superior visual acuity gain over standard laser in patients with visual impairment due to DME. Visual acuity gains were associated with significant gains in VFQ-25 scores. At 1 year, no differences were detected between the ranibizumab and ranibizumab + laser arms. Ranibizumab monotherapy and combined with laser had a safety profile in DME similar to that in age-related macular degeneration.Financial Disclosure(s)Proprietary or commercial disclosure may be found after the references. To demonstrate superiority of ranibizumab 0.5 mg monotherapy or combined with laser over laser alone based on mean average change in best-corrected visual acuity (BCVA) over 12 months in diabetic macular edema (DME). A 12-month, randomized, double-masked, multicenter, laser-controlled phase III study. We included 345 patients aged ≥18 years, with type 1 or 2 diabetes mellitus and visual impairment due to DME. Patients were randomized to ranibizumab + sham laser (n = 116), ranibizumab + laser (n = 118), or sham injections + laser (n = 111). Ranibizumab/sham was given for 3 months then pro re nata (PRN); laser/sham laser was given at baseline then PRN (patients had scheduled monthly visits). Mean average change in BCVA from baseline to month 1 through 12 and safety. Ranibizumab alone and combined with laser were superior to laser monotherapy in improving mean average change in BCVA letter score from baseline to month 1 through 12 (+6.1 and +5.9 vs +0.8; both P<0.0001). At month 12, a significantly greater proportion of patients had a BCVA letter score ≥15 and BCVA letter score level >73 (20/40 Snellen equivalent) with ranibizumab (22.6% and 53%, respectively) and ranibizumab + laser (22.9% and 44.9%) versus laser (8.2% and 23.6%). The mean central retinal thickness was significantly reduced from baseline with ranibizumab (−118.7 μm) and ranibizumab + laser (−128.3 μm) versus laser (−61.3 μm; both P<0.001). Health-related quality of life, assessed through National Eye Institute Visual Function Questionnaire (NEI VFQ-25), improved significantly from baseline with ranibizumab alone and combined with laser (P<0.05 for composite score and vision-related subscales) versus laser. Patients received ∼7 (mean) ranibizumab/sham injections over 12 months. No endophthalmitis cases occurred. Increased intraocular pressure was reported for 1 patient each in the ranibizumab arms. Ranibizumab monotherapy or combined with laser was not associated with an increased risk of cardiovascular or cerebrovascular events in this study. Ranibizumab monotherapy and combined with laser provided superior visual acuity gain over standard laser in patients with visual impairment due to DME. Visual acuity gains were associated with significant gains in VFQ-25 scores. At 1 year, no differences were detected between the ranibizumab and ranibizumab + laser arms. Ranibizumab monotherapy and combined with laser had a safety profile in DME similar to that in age-related macular degeneration.

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Effects of Medical Therapies on Retinopathy Progression in Type 2 Diabetes

2010-06-30

We investigated whether intensive glycemic control, combination therapy for dyslipidemia, and intensive blood-pressure control would limit the progression of diabetic retinopathy in persons with type 2 diabetes. Previous data suggest … We investigated whether intensive glycemic control, combination therapy for dyslipidemia, and intensive blood-pressure control would limit the progression of diabetic retinopathy in persons with type 2 diabetes. Previous data suggest that these systemic factors may be important in the development and progression of diabetic retinopathy.

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A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants

2015-12-21

Lars G. Fritsche , Wilmar Igl , Jessica N. Cooke Bailey +7 more

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The Effect of Long-Term Intensified Insulin Treatment on the Development of Microvascular Complications of Diabetes Mellitus

1993-07-29

Per Reichard , Bengt-Yngve Nilsson , Urban Rosenqvist

A cause-and-effect relation between blood glucose concentrations and microvascular complications in patients with insulin-dependent diabetes mellitus has not been established. A cause-and-effect relation between blood glucose concentrations and microvascular complications in patients with insulin-dependent diabetes mellitus has not been established.

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Vascular Endothelial Growth Factor in Ocular Fluid of Patients with Diabetic Retinopathy and Other Retinal Disorders

1994-12-01

Lloyd Paul Aiello , Robert L. Avery , Paul G. Arrigg +7 more

Retinal ischemia induces intraocular neovascularization, which often leads to glaucoma, vitreous hemorrhage, and retinal detachment, presumably by stimulating the release of angiogenic molecules. Vascular endothelial growth factor (VEGF) is an … Retinal ischemia induces intraocular neovascularization, which often leads to glaucoma, vitreous hemorrhage, and retinal detachment, presumably by stimulating the release of angiogenic molecules. Vascular endothelial growth factor (VEGF) is an endothelial-cell-specific angiogenic factor whose production is increased by hypoxia.

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A Randomized, Placebo-Controlled, Clinical Trial of High-Dose Supplementation With Vitamins C and E, Beta Carotene, and Zinc for Age-Related Macular Degeneration and Vision Loss

2001-10-01

<h3>Background</h3> Observational and experimental data suggest that antioxidant and/or zinc supplements may delay progression of age-related macular degeneration(AMD) and vision loss. <h3>Objective</h3> To evaluate the effect of high-dose vitamins C … <h3>Background</h3> Observational and experimental data suggest that antioxidant and/or zinc supplements may delay progression of age-related macular degeneration(AMD) and vision loss. <h3>Objective</h3> To evaluate the effect of high-dose vitamins C and E, beta carotene, and zinc supplements on AMD progression and visual acuity. <h3>Design</h3> The Age-Related Eye Disease Study, an 11-center double-masked clinical trial, enrolled participants in an AMD trial if they had extensive small drusen, intermediate drusen, large drusen, noncentral geographic atrophy, or pigment abnormalities in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye. At least 1 eye had best-corrected visual acuity of 20/32 or better. Participants were randomly assigned to receive daily oral tablets containing:(1) antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg); (2) zinc, 80 mg, as zinc oxide and copper, 2 mg, as cupric oxide;(3) antioxidants plus zinc; or (4) placebo. <h3>Main Outcome Measures</h3> (1) Photographic assessment of progression to or treatment for advanced AMD and (2) at least moderate visual acuity loss from baseline (≥15 letters). Primary analyses used repeated-measures logistic regression with a significance level of .01, unadjusted for covariates. Serum level measurements, medical histories, and mortality rates were used for safety monitoring. <h3>Results</h3> Average follow-up of the 3640 enrolled study participants, aged 55-80 years, was 6.3 years, with 2.4% lost to follow-up. Comparison with placebo demonstrated a statistically significant odds reduction for the development of advanced AMD with antioxidants plus zinc (odds ratio [OR], 0.72; 99% confidence interval [CI], 0.52-0.98). The ORs for zinc alone and antioxidants alone are 0.75 (99% CI, 0.55-1.03) and 0.80 (99% CI, 0.59-1.09), respectively. Participants with extensive small drusen, nonextensive intermediate size drusen, or pigment abnormalities had only a 1.3% 5-year probability of progression to advanced AMD. Odds reduction estimates increased when these 1063 participants were excluded (antioxidants plus zinc: OR, 0.66; 99% CI, 0.47-0.91; zinc: OR, 0.71; 99% CI, 0.52-0.99; antioxidants: OR, 0.76; 99% CI, 0.55-1.05). Both zinc and antioxidants plus zinc significantly reduced the odds of developing advanced AMD in this higher-risk group. The only statistically significant reduction in rates of at least moderate visual acuity loss occurred in persons assigned to receive antioxidants plus zinc (OR, 0.73; 99% CI, 0.54-0.99). No statistically significant serious adverse effect was associated with any of the formulations. <h3>Conclusions</h3> Persons older than 55 years should have dilated eye examinations to determine their risk of developing advanced AMD. Those with extensive intermediate size drusen, at least 1 large druse, noncentral geographic atrophy in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye, and without contraindications such as smoking, should consider taking a supplement of antioxidants plus zinc such as that used in this study.

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Ranibizumab for Diabetic Macular Edema

2012-02-11

Quan Dong Nguyen , David M. Brown , Dennis M. Marcus +7 more

Retinopathy and Nephropathy in Patients with Type 1 Diabetes Four Years after a Trial of Intensive Therapy

2000-02-10

John M. Lachin , Saul Genuth , Patricia A. Cleary +2 more

Among patients with type 1 diabetes mellitus, intensive therapy (with the aim of achieving near-normal blood glucose and glycosylated hemoglobin concentrations [hemoglobin A1c]) markedly reduces the risk of microvascular complications … Among patients with type 1 diabetes mellitus, intensive therapy (with the aim of achieving near-normal blood glucose and glycosylated hemoglobin concentrations [hemoglobin A1c]) markedly reduces the risk of microvascular complications as compared with conventional therapy. To assess whether these benefits persist, we compared the effects of former and intensive conventional therapy on the recurrence and severity of retinopathy and nephropathy for four years after the end of the Diabetes Control and Complications Trial (DCCT).At the end of the DCCT, the patients in the conventional-therapy group were offered intensive therapy, and the care of all patients was transferred to their own physicians. Retinopathy was evaluated on the basis of centrally graded fundus photographs in 1208 patients during the fourth year after the DCCT ended, and nephropathy was evaluated on the basis of urine specimens obtained from 1302 patients during the third or fourth year, approximately half of whom were from each treatment group.The difference in the median glycosylated hemoglobin values between the conventional-therapy and intensive-therapy groups during the 6.5 years of the DCCT (average, 9.1 percent and 7.2 percent, respectively) narrowed during follow-up (median during 4 years, 8.2 percent and 7.9 percent, respectively, P<0.001). Nevertheless, the proportion of patients who had worsening retinopathy, including proliferative retinopathy, macular edema, and the need for laser therapy, was lower in the intensive-therapy group than in the conventional-therapy group (odds reduction, 72 percent to 87 percent, P<0.001). The proportion of patients with an increase in urinary albumin excretion was significantly lower in the intensive-therapy group.The reduction in the risk of progressive retinopathy and nephropathy resulting from intensive therapy in patients with type 1 diabetes persists for at least four years, despite increasing hyperglycemia.

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Optical coherence tomography angiography

2017-12-09

Richard F. Spaide , James G. Fujimoto , Nadia K. Waheed +2 more

Optical coherence tomography (OCT) was one of the biggest advances in ophthalmic imaging. Building on that platform, OCT angiography (OCTA) provides depth resolved images of blood flow in the retina … Optical coherence tomography (OCT) was one of the biggest advances in ophthalmic imaging. Building on that platform, OCT angiography (OCTA) provides depth resolved images of blood flow in the retina and choroid with levels of detail far exceeding that obtained with older forms of imaging. This new modality is challenging because of the need for new equipment and processing techniques, current limitations of imaging capability, and rapid advancements in both imaging and in our understanding of the imaging and applicable pathophysiology of the retina and choroid. These factors lead to a steep learning curve, even for those with a working understanding dye-based ocular angiography. All for a method of imaging that is a little more than 10 years old. This review begins with a historical account of the development of OCTA, and the methods used in OCTA, including signal processing, image generation, and display techniques. This forms the basis to understand what OCTA images show as well as how image artifacts arise. The anatomy and imaging of specific vascular layers of the eye are reviewed. The integration of OCTA in multimodal imaging in the evaluation of retinal vascular occlusive diseases, diabetic retinopathy, uveitis, inherited diseases, age-related macular degeneration, and disorders of the optic nerve is presented. OCTA is an exciting, disruptive technology. Its use is rapidly expanding in clinical practice as well as for research into the pathophysiology of diseases of the posterior pole.

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Complement Factor H Polymorphism and Age-Related Macular Degeneration

2005-03-11

Albert O. Edwards , Robert Ritter , Kenneth J. Abel +3 more

Age-related macular degeneration (AMD) is a common, late-onset, and complex trait with multiple risk factors. Concentrating on a region harboring a locus for AMD on 1q25-31, the ARMD1 locus, we … Age-related macular degeneration (AMD) is a common, late-onset, and complex trait with multiple risk factors. Concentrating on a region harboring a locus for AMD on 1q25-31, the ARMD1 locus, we tested single-nucleotide polymorphisms for association with AMD in two independent case-control populations. Significant association ( P = 4.95 × 10 -10 ) was identified within the regulation of complement activation locus and was centered over a tyrosine-402 → histidine-402 protein polymorphism in the gene encoding complement factor H. Possession of at least one histidine at amino acid position 402 increased the risk of AMD 2.7-fold and may account for 50% of the attributable risk of AMD.

Age-related macular degeneration

2018-09-01

Paul Mitchell , Gerald Liew , Bamini Gopinath +1 more

Diabetic retinopathy

2010-06-29

Ning Cheung , Paul Mitchell , Tien Yin Wong

Photocoagulation for Diabetic Macular Edema

1985-12-01

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Ophthalmology HomeNew OnlineCurrent … Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Ophthalmology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Ophthalmology journal

Diabetic Retinopathy

2012-03-28

David A. Antonetti , Ronald Klein , Thomas W. Gardner

The incidence of diabetes is increasing, but that of diabetic retinopathy is falling, probably owing to better management of glucose levels, lipid abnormalities, and hypertension. Clinical trials of VEGF and … The incidence of diabetes is increasing, but that of diabetic retinopathy is falling, probably owing to better management of glucose levels, lipid abnormalities, and hypertension. Clinical trials of VEGF and PPAR-α inhibitors are improving vision and providing insights into pathogenesis.

Age-related macular degeneration

2012-05-01

Laurence Shen Lim , Paul Mitchell , Johanna M. Seddon +2 more

Age-Related Macular Degeneration

2008-06-11

Rama D. Jager , William F. Mieler , Joan W. Miller

Age-related macular degeneration is the leading cause of irreversible blindness in people 50 years of age or older in the developed world. This article reviews the clinical and histopathological features … Age-related macular degeneration is the leading cause of irreversible blindness in people 50 years of age or older in the developed world. This article reviews the clinical and histopathological features of age-related macular degeneration and its genetics and epidemiology and discusses current management options and research advances.

Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus: Diabetes Control and Complications Trial

1994-08-01

Diabetes Control

Metabolic reprogramming of the neovascular niche promotes regenerative angiogenesis in proliferative retinopathy

2025-06-25

Gaël Cagnone , Sheetal Pundir , Charlotte Betus +7 more | Nature Communications

Healthy blood vessels supply neurons to preserve metabolic function. In blinding proliferative retinopathies (PRs), pathological neovascular tufts often emerge in lieu of needed physiological revascularization. Here we show that metabolic … Healthy blood vessels supply neurons to preserve metabolic function. In blinding proliferative retinopathies (PRs), pathological neovascular tufts often emerge in lieu of needed physiological revascularization. Here we show that metabolic shifts in the neovascular niche define angiogenic fate. Fatty acid oxidation (FAO) metabolites accumulated in human and murine retinopathy samples. Neovascular tufts with a distinct single-cell transcriptional signature highly expressed FAO enzymes. The deletion of Sirt3, an FAO regulator, shifted the neovascular niche metabolism from FAO to glycolysis and suppressed tuft formation. This metabolic transition increased Vegf expression in astrocytes and reprogrammed pathological neovessels to a physiological phenotype, hastening vascular regeneration of the ischemic retina and improving vision. Hence, strategies to change the metabolic environment of vessels could promote a regenerative phenotype in vascular diseases.

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Comparative treatment burden of intravitreal injection versus visit frequency in patients with exudative age‐related macular degeneration

2025-06-24

Lisa‐Maria Weissenbacher , R. Schmidt , Pia Veronika Vécsei‐Marlovits +1 more | Acta Ophthalmologica

Lipoprotein (a) in the Development and Progression of Diabetic Retinopathy: A Systematic Review and Meta-Analysis

2025-06-24

Stamatios Lampsas , Vaia Lambadiari , Chrysa Agapitou +4 more | Medicina

Background and Objectives: Diabetic retinopathy (DR) is a significant complication of Diabetes Mellitus. Several studies have indicated Lipoprotein (a) [Lp(a)] plays a role in atherosclerotic alterations. Materials and Methods: This … Background and Objectives: Diabetic retinopathy (DR) is a significant complication of Diabetes Mellitus. Several studies have indicated Lipoprotein (a) [Lp(a)] plays a role in atherosclerotic alterations. Materials and Methods: This meta-analysis/systematic review aims to investigate the connection between Lp(a) and DR. All relevant studies indexed in PubMed and Scopus from up to January 2025 were included. A total of 29 studies (7007 subjects) were included, and the results were synthesized according to the PRISMA Guidelines. The results are presented as standardized mean differences (SMDs) with 95% confidence intervals (CIs) derived using random effects models. Results: The mean age of the included subjects was 52.6 ± 9.4 years, with 52.5% being male. The primary analysis included 25 observational studies involving a total of 6291 subjects (2770 patients with DR vs. 3521 controls). Notably, Lp(a) levels were significantly higher in patients with DR compared to those in controls, with an SMD of 0.85 (95% CI: 0.48–1.22; p < 0.001, I2 = 98%). Interestingly, a secondary analysis of the patients with Proliferative Diabetic Retinopathy (PDR) and Non-Proliferative Diabetic Retinopathy (NPDR) yielded an SMD of 0.28 (95% CI: 0.09–0.47; p = 0.004, I2 = 97%) between the two compared groups. In this analysis, a total of 1066 patients (465 PDR patients vs. 601 NPDR patients) were included. Conclusions: Elevated Lp(a) levels may have a compelling relationship with the development and progression of DR based on the evidence analyzed.

Prevalence of vision impairment among patients with diabetes mellitus in sub-Saharan Africa: A systematic review and meta-analysis

2025-06-24

Altaseb Beyene Kassaw , Addis Alem Hadigu , Abiy Abebe +5 more | PLoS ONE

Background Diabetes mellitus is a growing global public health challenge, especially in low- and middle-income regions like sub-Saharan Africa, where healthcare resources are often limited. One of its most debilitating … Background Diabetes mellitus is a growing global public health challenge, especially in low- and middle-income regions like sub-Saharan Africa, where healthcare resources are often limited. One of its most debilitating complications is vision impairment, which significantly impacts the quality of life, productivity, and independence of individuals. Although several studies have assessed the prevalence of vision impairment among individuals with diabetes in sub-Saharan Africa, their findings have been inconsistent and fragmented across different areas. A comprehensive synthesis of this evidence is crucial for informing healthcare planning, early screening, and management strategies. This study aimed to systematically review and synthesize the existing evidence on the prevalence of vision impairment among patients with diabetes mellitus in the region. Methods A literature exploration was done in an electronic database such as PubMed, Google Scholar, Web of Science, Hinary, and African Journals Online. We included all observational studies reporting the prevalence of vision loss among diabetes mellitus patients in Sub-Saharan Africa. A random-effect meta-analysis model was computed to estimate the pooled prevalence of vision impairment. I 2 test and Cochrane Q test statistics were used to assess the heterogeneity of the studies. Subgroup analysis was done based on the countries where the research was conducted. STATA Version 16 statistical software was used for data analysis. Publication bias was examined by funnel plots and Egger’s tests. Results Only 26 studies with 12508 participants, contributing data from 14 countries within Sub-Saharan Africa, met the inclusion criteria for the final analysis. The overall pooled prevalence of visual impairment was found to be 29% (95% CI: 22%−35%). Heterogeneity was observed among included studies ( p < 0.001 for high I 2 values). Subgroup analysis revealed the source of heterogeneity in the studies carried out in Ethiopia (I 2 = 99.2%, p = < 0.001), Nigeria (I 2 = 94.59%, p = < 0.001), and Zambia (I 2 = 77.34%, p = 0.036). Conclusion The findings of this study indicated that the pooled prevalence of vision impairment among diabetes mellitus patients is relatively higher. It can be concluded that diabetes mellitus patients should be managed properly to prevent visual impairment. Early detection of visual impairment through screening and regular follow-up is recommended to reduce as well as control the burden of visual impairment and its impact on the diabetic population.

Effects of <scp>VEGFA</scp> and <scp>ANGPT2</scp> Antibodies on the Activation of Microglia in the Early Stages of Streptozotocin‐Induced Pathogenesis of Diabetic Retinopathy

2025-06-24

Toshiro Iwagawa , Yuta Inokuchi , Kosuke Saita +4 more | Genes to Cells

ABSTRACT Diabetic retinopathy (DR) is known as a microvascular complication, in which various inflammatory symptoms, including activation of microglia, are observed. A model of hyperglycemia resembling type 1 diabetes mellitus … ABSTRACT Diabetic retinopathy (DR) is known as a microvascular complication, in which various inflammatory symptoms, including activation of microglia, are observed. A model of hyperglycemia resembling type 1 diabetes mellitus (DM) induced in mice by intraperitoneal injection of streptozotocin (STZ) has been widely used. We examined the effects of anti‐ vascular endothelial growth factor A (VEGFA) and anti‐angiopoietin‐2 (ANGPT2) antibodies in addition to a bispecific antibody against VEGFA and ANGPT2 by intravitreously administrated to the eyes on early signs, especially the activation of microglia in STZ‐treated mice eyes. After 14 weeks of STZ administration, alterations in activity by ERG and CD31 staining patterns were not observed. Although a difference in the number of microglia in the retina between normal and STZ‐model retinas was not observed, the morphology of microglia had changed from ramified in control to amoeboid shape in STZ model at 4 days after the antibodies injection. Detailed morphological examination showed decreases in area, ramification index, and tree length in the STZ‐model retinas compared with normal retinas. Recovery from these decreases was demonstrated mainly by the administration of the bispecific antibody. These results suggest that anti‐VEGFA/ANGPT2 therapy may suppress the activation of microglia in the early stages of DR.

Treatment Efficacy of a Dual Release of Aflibercept and Dexamethasone From a Single Hydrogel Drug Delivery System in a Rodent Model

2025-06-24

Kayla M. Rudeen , Chryssa M. Maloney , Katherine L. Lydon +3 more | Translational Vision Science & Technology

Age-related macular degeneration (AMD) is the leading cause of vision loss for the elderly population. Wet AMD, which accounts for approximately 15% of AMD cases, is characterized by abnormal blood … Age-related macular degeneration (AMD) is the leading cause of vision loss for the elderly population. Wet AMD, which accounts for approximately 15% of AMD cases, is characterized by abnormal blood vessel growth from the choroid into the subretinal space. Although intravitreal anti-vascular endothelial growth factor (VEGF) agents have become the standard of care for wet AMD, there is a growing subset of patients who do not fully respond to monotherapy anti-VEGF treatment. In previously published reports, corticosteroids have shown improvements in treatment efficacy when administered with anti-VEGF in a subset of non-responders to anti-VEGF monotherapy. A combination dexamethasone and aflibercept drug delivery system (Combo-DDS) was evaluated in a laser-induced rodent model of choroidal neovascularization (CNV). Longitudinal monitoring was done through week 22 using fluorescein angiography (FA) and spectral domain optical coherence tomography (SD-OCT). Multi-Otsu thresholding was used to quantify the lesion area based on late-phase FA images. In addition, preliminary safety and biocompatibility of the Combo-DDS were evaluated by intraocular pressure (IOP) measurements, electroretinogram (ERG), and histology (n = 6 eyes/group). In the laser-induced CNV model, CNV lesions (n = 28-36 lesions/group) were monitored longitudinally. Combo-DDS showed a regression in lesion size starting at week 2 that continued through the end of study. IOP, ERG, and histology showed preliminary safety and biocompatibility of the Combo-DDS. This study demonstrated that Combo-DDS maintained treatment efficacy in a laser-induced CNV rodent model for 6 months. The Combo-DDS shows the potential to eliminate the need for separate dosing regiments of anti-VEGF and corticosteroids for non-responders to anti-VEGF monotherapy.

Crystal structure analysis of oxygen-induced degradation occurring in rsCherry

2025-06-24

Thi Yen Hang Bui , Ludovic Pecqueur , Peter Dedecker +1 more | Acta Crystallographica Section F Structural Biology Communications

rsCherry was one of the first reversibly photoswitchable variants to be developed from mCherry. However, its practical applications have been limited due to several inherent drawbacks. We have recently shown … rsCherry was one of the first reversibly photoswitchable variants to be developed from mCherry. However, its practical applications have been limited due to several inherent drawbacks. We have recently shown that the purified protein undergoes oxygen-induced chromophore degradation in solution, resulting in the progressive loss of its fluorescence and color. In this work, we present four crystal structures of rsCherry that exhibit varying degrees of degradation. Our structural analysis indicates that oxygen-induced degradation of rsCherry predominantly affects the chromophore without altering the protein backbone. Changes were only observed in the conformation of Lys70, confirming the crucial role of this residue in chromophore damage in rsCherry. Overall, this study provides valuable insights into the structural changes triggered by oxygen exposure in rsCherry, offering suggestions for the development of stable red fluorescent proteins with improved resistance to oxidative damage.

Apolipoprotein M attenuates age-related macular degeneration phenotypes via sphingosine-1-phosphate signaling and lysosomal lipid catabolism

2025-06-24

Tae Jun Lee , Andrea Santeford , Kristen M. Pitts +7 more | Nature Communications

Age-related macular degeneration (AMD) is a leading cause of blindness in people over 50. AMD and cardiovascular disease share risk factors including age, impaired lipid metabolism, and extracellular lipid deposition. … Age-related macular degeneration (AMD) is a leading cause of blindness in people over 50. AMD and cardiovascular disease share risk factors including age, impaired lipid metabolism, and extracellular lipid deposition. Because of its importance in age-related diseases, we hypothesize that apolipoprotein M (ApoM), a lipocalin that binds sphingosine-1-phosphate (S1P), might restore lipid homeostasis and retinal function in AMD. In support, we find that human patients with AMD demonstrate significantly reduced ApoM compared to controls. In mice with impaired retinal cholesterol efflux, ApoM improves retinal pigment epithelium (RPE) function and lipotoxicity in an S1P- and S1P receptor 3-dependent manner. Ultrastructural evidence of enhanced melanosome-lipid droplet interactions led us to hypothesize and demonstrate that ApoM-S1P signaling drives RPE-specific lysosomal lipid catabolism. RPE-specific knockout of lysosomal acid lipase recapitulates features of AMD. Our study defines a novel role for ApoM/S1P signaling in AMD driven by RPE lipotoxicity, mediated by cell-autonomous lysosomal lipid catabolism.

Role of Preoperative and Postoperative Intravitreal Anti-VEGF Agents in Managing Diabetic Macular Edema and Diabetic Retinopathy

2025-06-23

Angeline Julius , Suresh Malakondaiah , Ramalakshmi Subbarayalu +1 more | SN Comprehensive Clinical Medicine

Serum Lipid Biomarkers as Predictors for Age-Related Macular Degeneration Risk: A Cross-Sectional Analysis from the Beichen Eye Study

2025-06-23

Gang Zou , Fei Gao , Limin Zhang +3 more | Research Square (Research Square)

<title>Abstract</title> <bold>Background:</bold> This population-based study aimed to investigate the associations between serum lipid biomarkers and the prevalence of age-related macular degeneration (AMD). <bold>Methods:</bold> This cross-sectional study analyzed data from 4748 … <title>Abstract</title> <bold>Background:</bold> This population-based study aimed to investigate the associations between serum lipid biomarkers and the prevalence of age-related macular degeneration (AMD). <bold>Methods:</bold> This cross-sectional study analyzed data from 4748 subjects over 50 years old who were enrolled in the Beichen Eye Study. TG/HDL-c, HDL-c/LDL-c, the neutrophil/HDL-c ratio (NHR), the lymphocyte/HDL-c ratio (LHR), the monocyte/HDL-c ratio (MHR), the platelet/HDL-c ratio (PHR), the platelet/lymphocyte ratio (PLR), and the neutrophil/lymphocyte ratio (NLR)were assessed. Additionally, basic information, BMI, history of disease related to lipid metabolism, living habits and history of statin use were collected. <bold>Results:</bold> This study included 4748 participants, and 1245 of whom were diagnosed with AMD. The overall prevalence of AMD was 26.22%. The prevalence of AMD increased significantly with age (Z=-6.58, P<0.001). TG/HDL-c and HDL-c/LDL-c were significantly associated with the incidence of AMD (Z=-2.71, P=0.007; Z=-1.98, P=0.047, respectively). Multivariate logistic regression revealed that a high TG/HDL-c ratio (OR=0.80, P<0.05) and high NHR (OR=0.83, P<0.05) were both inversely associated with AMD risk, indicating protective effects. Elevated TG levels were also found to be protective against AMD (OR=0.80, P<0.05). Elevated HDL-c was associated with a paradoxical increase in AMD risk, especially in the second tertile (OR=1.04, 95% CI=0.89–1.22; P<0.05). <bold>Conclusions:</bold> This study suggested that an elevated TG/HDL-c ratio and NHR serve as protective biomarkers for AMD, with higher TG levels showing a protective effect. Conversely, HDL-c levelsdemonstrated a paradoxical association with AMD risk.These findings provide insights into the complex role of lipid metabolism in AMD pathogenesis and suggest potential biomarkers for AMD risk prediction.

Mechanism of PMC (2,2,5,7,8-pentamethyl-6-chromanol), a sterically hindered phenol antioxidant, in rescuing oxidized low-density lipoprotein-induced cytotoxicity in human retinal pigment epithelial cells

2025-06-22

Suman Chaudhary , Jean Moon , Zhengping Hu +5 more | bioRxiv (Cold Spring Harbor Laboratory)

Geographic atrophy or late stage dry age-related macular degeneration (AMD) is characterized by drusen deposition and progressive retinal pigment epithelium (RPE) degeneration, leading to irreversible vision loss. The formation of … Geographic atrophy or late stage dry age-related macular degeneration (AMD) is characterized by drusen deposition and progressive retinal pigment epithelium (RPE) degeneration, leading to irreversible vision loss. The formation of drusen leads to dyshomeostasis, oxidative stress and irreversible damage to RPE. In this study, we used an in vitro model of oxidized-low density lipoproteins (ox-LDL) induced human RPE damage/death model to investigate the mechanism whereby a sterically hindered phenol antioxidant compound, PMC (2,2,5,7,8-pentamethyl-6-chromanol) protects RPE against ox-LDL-induced damage. We show that PMC exerts its protective effect by preventing the upregulation of stress-responsive heme oxygenase-1 (HMOX1/HO-1) and NAD(P)H:quinone oxidoreductase (NQO1) at mRNA and protein levels. This effect was due to PMC mediated blockade of ROS generation, which in turn blocked nuclear translocation of the Nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor, ultimately preventing the upregulation of antioxidant response elements (ARE), including HMOX1 and NQO1. A key role for HO-1 was demonstrated when the protective effect of PMC was inhibited by the knockdown of HMOX1. Additionally, treatment of PMC under different experimental conditions and time points revealed that the continuous presence of PMC is required for optimal protection against ox-LDL-induced cytotoxicity, defining the cellular pharmacokinetics of the molecule. Our data demonstrate the involvement of a key antioxidant pathway through which PMC mitigates oxidative stress induced by ox-LDL and provides a potential therapeutic strategy to suppress RPE degeneration/damage during AMD progression.

Safety Evaluation of Bilateral Same-Day Intravitreal Injection of Faricimab

2025-06-22

Michael Karampelas , Irini Chatziralli , Dimitrios Karagiannis | Ophthalmology and Therapy

Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is the most commonly performed ophthalmic procedure. Many retinal specialists routinely perform same-day bilateral intravitreal anti-VEGF injections, in order to reduce … Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is the most commonly performed ophthalmic procedure. Many retinal specialists routinely perform same-day bilateral intravitreal anti-VEGF injections, in order to reduce the burden to patient and clinic time. There are several reports demonstrating the safety of bilateral same-day treatment with ranibizumab, bevacizumab, and aflibercept, but currently, there are no reports regarding faricimab. The purpose of this study is to report safety outcomes in a cohort of patients who received bilateral same-day faricimab intravitreal injections. This is a retrospective observational study that included patients who received bilateral same-day faricimab and had a follow-up of at least 6 months. All patients were treated by 4 monthly faricimab injections as a loading dose and subsequently followed up at monthly intervals. All intravitreal injections were done in a sterile room and the second injection was treated as a separate procedure. One hundred eyes from 50 patients were included in the study. The mean follow-up period was 7 months, during which a total of 487 intravitreal injections of faricimab were done. During the follow-up period, five patients (10%) presented with minor ophthalmic issues. There were no cases of endophthalmitis and no patients reported a cerebrovascular, cardiovascular, or thromboembolic event. Our study showed that bilateral same-day intravitreal injection of faricimab appeared to be well tolerated in this limited cohort and is the preferred approach in our practice. Larger studies with longer follow-up will be required in order to support our findings.

Increased macular atrophy area with photodynamic therapy over intravitreal aflibercept at 2-year follow-up of pachychoroid neovasculopathy

2025-06-21

Hirokazu Kojima , Chieko Shiragami , Ayana Yamashita +4 more | Japanese Journal of Ophthalmology

Sodium-glucose cotransporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors on diabetic macular edema and the need for intravitreal injection

2025-06-20

Yoo-Ri Chung , Eunzee Lee , Kihwang Lee | International Journal of Ophthalmology

AIM: To investigate the effects of dipeptidyl peptidase-4 inhibitors (DPP4i) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) on diabetic macular edema (DME) and the need for intravitreal injections (IVT) in patients with … AIM: To investigate the effects of dipeptidyl peptidase-4 inhibitors (DPP4i) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) on diabetic macular edema (DME) and the need for intravitreal injections (IVT) in patients with type 2 diabetes. METHODS: Data were retrospectively collected from the medical records of patients with diabetic retinopathy (DR) taking either DPP4i or SGLT2i as secondary oral hypoglycemic agents in addition to metformin between January 2019 and July 2022. We compared the prevalence of DME and the need for IVT among patients treated with DPP4i or SGLT2i. Propensity score matching was performed using the following variables: age, duration of diabetes, blood glucose control (HbA1c) level, and severity of DR. RESULTS: A total of 268 patients with DR were included in this study. More DPP4i users needed IVT than SGLT2i users (35.3% vs 18.0%, P=0.011), while the prevalence of DME was not different. The use of SGLT2i was associated with a lower need for IVT than DPP4i [odds ratio (OR) 0.404, 95% confidence interval (CI) 0.198–0.823], and similar trends were observed after propensity score matching (OR 0.419, 95%CI 0.181–0.970). However, this tendency was not significant in multiple logistic regressions. For DME, the use of DPP4i was not a significant risk factor compared to SGLT2i. CONCLUSION: The use of SGLT2i may be associated with a lower need for IVT for overall DR complications, while other factors may contribute to this effect. The effect of SGLT2i on the prevention of DME is not evident.

Enhancement of retinal Müller glia’s phagocytic activity against hard exudates by conbercept via activation of PPARγ-CD36 axis in diabetic retinopathy

2025-06-20

Yingying Zhu , Hai Xie , Yinping Liu +4 more | International Journal of Ophthalmology

AIM: To investigate the effects and the underlying mechanism(s) of conbercept on the phagocytosis of hard exudates (HEs) by Müller glia in diabetic retinopathy (DR). METHODS: Twenty-one eyes from 17 … AIM: To investigate the effects and the underlying mechanism(s) of conbercept on the phagocytosis of hard exudates (HEs) by Müller glia in diabetic retinopathy (DR). METHODS: Twenty-one eyes from 17 patients with diabetic macular edema (DME) underwent optical coherence tomography (OCT) imaging to examine the changes of HEs before and after intravitreal conbercept injection (IVC). In vitro, rat retinal Müller cell line (rMC-1) was cultured under high glucose and treated with oxidized low-density lipoprotein (Ox-LDL) with or without conbercept. Phagocytosis was analysed with immunofluorescence, flow cytometry, and Western blot. Expressions of scavenger receptors (LOX-1, CD36) were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Conbercept's effects on vascular endothelial growth factor A (VEGF-A), VEGFR2, inflammation (NF-κB, IL-6, iNOS), and oxidative stress (ROS) were evaluated with Western blot and immunofluorescence. RESULTS: The area of HEs showed minimal change after the first IVC (1.39±1.41 to 1.38±1.3 mm2, P=0.938), but significantly decreased after the third IVC (0.45±0.66 mm2, P=0.002). In vitro, conbercept enhanced the phagocytosis of Ox-LDL by rMC-1 cells under high glucose condition. Conbercept reduced ROS and inflammation (NF-κB, IL-6, iNOS) in high glucose-treated rMC-1 cells by suppression of VEGF/VEGFR2 pathway. The inhibition of NF-κB by conbercept further activated PPARγ-CD36 axis, increasing CD36 expression and promoting Ox-LDL uptake, thereby facilitating the clearance of HEs. CONCLUSION: Conbercept reduces HEs in DR by enhancing Müller glia phagocytosis possibly through activating PPARγ-CD36 axis, which is mediated by inhibition of VEGF signaling. Modulation of Müller glia phagocytic capacity might provide a novel therapeutic strategy to treat DR and DME.

Pericytes as Key Players in Retinal Diseases: A Comprehensive Narrative Review

2025-06-20

Fabiana D’Esposito , F. Cappellani , F Visalli +7 more | Biology

Pericytes, specialized mural cells surrounding microvessels, play a crucial role in maintaining vascular homeostasis and function across various organs, including the eye. These versatile cells regulate blood flow, support the … Pericytes, specialized mural cells surrounding microvessels, play a crucial role in maintaining vascular homeostasis and function across various organs, including the eye. These versatile cells regulate blood flow, support the integrity of the blood–retinal barrier, and contribute to angiogenesis. Recent advancements in molecular and cellular biology have revealed the heterogeneity of pericytes and their critical involvement in ocular physiology and pathology. This review provides a comprehensive analysis of pericyte functions in ocular health and their implications in diseases such as diabetic retinopathy, age-related macular degeneration, glaucoma, and retinal vein occlusion. Pericyte dysfunction is implicated in vascular instability, neurovascular coupling failure, inflammation, and pathological neovascularization, contributing to vision-threatening disorders. The review further explores recent findings on pericyte-targeted therapies, including pharmacological agents, gene therapy, and cell-based approaches, aiming to restore pericyte function and preserve ocular health.

Disease control, visual and anatomic outcomes at week 48 of brolucizumab treatment in patients with previously suboptimal anatomically controlled neovascular age-related macular degeneration – The SWIFT study

2025-06-20

Aude Couturier , Eric H. Souied , Catherine Creuzot‐Garcher +7 more | Journal Français d Ophtalmologie

Active peptides of TSP-1 inhibit retinal angiogenesis through the CD36 pathway in a rat model of choroidal neovascularization

2025-06-20

Yadi Li , Aiping Deng , Kangwei Jiao +7 more | PLoS ONE

Background Choroidal neovascularization (CNV) is a key manifestation of intraocular neovascularization, and it is considered one of the main causes of blindness in ophthalmology. Additionally, multiple anti-vascular endothelial growth factor … Background Choroidal neovascularization (CNV) is a key manifestation of intraocular neovascularization, and it is considered one of the main causes of blindness in ophthalmology. Additionally, multiple anti-vascular endothelial growth factor (VEGF) drugs have been used as first-line treatment for CNV. However, several issues posed challenges to the anti-VEGF drugs, which were mainly composed of short duration of action, requirement for repeated injections, and complications. Thrombospondin-1 (TSP-1) is an endogenous protein that was found to regulate multiple biological processes within the body, and it has been proven to exhibit an inhibitory effect on neovascularization. Besides, the function of TSP-1 during the inhibition of neovascularization was currently considered to mainly focus on its type Ⅰ repeats (TSRs), which was attributed to the large molecular weight, complex structure, and possible unknown functions of TSP-1. Therefore, TSRs can be applied as targets and research directions for the further development and exploration of potential therapeutic drugs. Objectives Based on the type I repeats (TSRs) of thrombospondin-1 (TSP-1), amino acid sequences of different lengths were designed and synthesized in this study, named as VR-9 VR-10、VR-11、VR-12、VR-13. The objective was to explore the effects of the above five peptides on angiogenesis in Chori-retinal neovascularization, alongside the screening of the best peptides and the deep exploration into the underlying mechanism, aimed to provide a basis for the development and application of peptide drugs in the treatment of CNV. Methods Wound healing, CCK-8, and 5-ethynyl-2′-deoxyuridine (EdU) assays were employed to evaluate the proliferation and migration ability of cells. CRISPR-Cas9 technology was utilized to establish CD36 knockdown cell lines, alongside the conduction of qPCR to verify the efficiency of gene knockdown. The expression levels of VEGF and CD31 in RF/6A cells and rats were assessed by Western blot. Additionally, Hematoxylin and eosin (HE) staining was performed to examine the structural integrity of the rat retina, while Fluorescein Isothiocyanate-Dextran Cardiac Perfusion (FITC) labeling was used to observe the occurrence and development of choroidal neovascularization (CNV). Results According to the wound-healing and CCK-8 assays, VR-13 was the most effective in inhibiting the proliferation and migration of endothelial cells. Furthermore, VR-13 peptide effectively inhibited the pathological development of CNV without the detection of retinal toxicity in the rat CNV model. Conclusions Overall, it was found that VR-13 exhibit significant effects on the inducing of apoptosis and the inhibition of the progression of angiogenesis by regulating the expression of VEGF and CD31 via CD36 signaling pathway.

Implications of Fatty Acids for Age-Related Macular Degeneration: Evidence and Recommendations

2025-06-19

Shivantika Bisen , Nikhlesh K. Singh | Cells

Age-related macular degeneration (AMD) is an ocular pathology in humans characterized by the buildup of lipid-rich extracellular deposits, which leads to retinal degeneration. In recent years, considerable effort has been … Age-related macular degeneration (AMD) is an ocular pathology in humans characterized by the buildup of lipid-rich extracellular deposits, which leads to retinal degeneration. In recent years, considerable effort has been made to observe the effect of dietary fatty acids on oxidative stress and inflammation. In continuation of this, much effort has been made to study the effect of dietary fatty acids on the pathogenesis of AMD. Although studies have shown that dietary fatty acids are effective against few forms of AMD, particularly wet AMD or neovascular AMD, no dietary lipids have shown any conclusive results for dry AMD or geographic AMD. It is therefore important to look for new lipids and lipoproteins that can be helpful in treating various stages of AMD. This article reviews the impact of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) on retinal health and the progression of AMD. Furthermore, this manuscript discusses all studies investigating the implications of fatty acids on AMD, which may be beneficial for future treatment strategies and dietary guidelines related to it. In conclusion, studies suggest that omega-3 PUFAs, particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), might provide protection against AMD, highlighting the necessity for additional clinical trials to evaluate their efficacy in the prevention and treatment of AMD.

EFFECTS OF FARICIMAB LOADING PHASE ON DIABETIC MACULAR EDEMA IN REAL-WORLD SETTING

2025-06-19

Alessandra Scampoli , Matteo Mario Carlà , Giulia Grieco +4 more | Retina

Purpose: To explore the functional and anatomic outcomes of eyes with resistant diabetic macular edema undergoing a loading phase of four intravitreal faricimab. Methods: Prospective research on 46 eyes with … Purpose: To explore the functional and anatomic outcomes of eyes with resistant diabetic macular edema undergoing a loading phase of four intravitreal faricimab. Methods: Prospective research on 46 eyes with diabetic macular edema previously treated with aflibercept or ranibizumab. At baseline (V0) and each monthly follow-up examination (V1–V4), we evaluated best-corrected visual acuity, optical coherence tomography, and angiography. Biomarkers such as central macular thickness, integrity of the ellipsoid zone/external limiting membrane, hyperreflective foci, disorganization of inner retina layers, and presence/absence of epiretinal membrane and subretinal fluid were collected, along with the vessel density (VD) in the superficial capillary plexi and deep capillary plexi and the foveal avascular zone area. Results: Best-corrected visual acuity significantly improved from baseline to V4 (0.55 ± 0.42 vs. 0.36 ± 0.30 logMAR; P = 0.03). Sixty-five percent of eyes showed visual improvement during follow-up, whereas 91% showed anatomic improvement, with a mean central macular thickness reduction of 108.4 µ m ( P = 0.0002). At V0, 20 eyes (43%) had irregularities of the external limiting membrane/ellipsoid zone complex compared with 14 eyes (30%) at V4 ( P = 0.28). Hyperreflective focis were visible in 87% of cases at baseline but reduced their prevalence up to 24 eyes (52%) at V4 ( P = 0.0005). Disorganization of inner retina layers was reported in eight eyes (17%) at baseline and resolved in three eyes. Foveal avascular zone area was stable during follow-up, as well as superficial capillary plexi's VD, whereas the parafoveal deep capillary plexi's VD significantly increased from V0 to V4 ( P = 0.04). Conclusion: Faricimab loading phase showed promising results in visual outcomes and structural improvement in resistant diabetic macular edema.

Microglia Promote Endothelial Cell Activation Through <scp>NSUN2</scp>‐Mediated <scp>SQLE m5C</scp> Modification in Diabetic Retinopathy

2025-06-19

Tingting Chen , Min Zhou , Yihua Su +7 more | The FASEB Journal

ABSTRACT To investigate the effect of retinal microglia on the quiescence‐activation balance and angiogenesis potential of endothelial cells in diabetic retinopathy (DR). Retinal microglia from diabetic mice were isolated and … ABSTRACT To investigate the effect of retinal microglia on the quiescence‐activation balance and angiogenesis potential of endothelial cells in diabetic retinopathy (DR). Retinal microglia from diabetic mice were isolated and cocultured with endothelial cells. The quiescence‐activation status of endothelial cells was determined by flow cytometry, EdU staining and expressions of activation markers including P21 and CDK1, and the angiogenesis potential was detected by tube formation assays. RNA sequencing was performed to identify the critical gene, which was regulated by inhibiting or overexpressing lentiviruses transfection. The concentration of cholesterol and its effect on the status and function of endothelial cells, as well as the signal pathways activation, were measured. The critical m5C modification related protein was identified using Western blotting and lentiviruses transfection. Retinal microglia isolated from diabetic mice impeded quiescence but promoted the activation of endothelial cells, and then subsequently enhanced the angiogenesis potential of endothelial cells. Besides, the expression of squalene epoxidase (SQLE) was significantly increased in endothelial cells cocultured with retinal microglia isolated from diabetic mice. Inhibiting SQLE expression in endothelial cells restrained their activation levels and angiogenesis potential, and overexpressing SQLE activated endothelial cells to facilitate angiogenesis. Mechanistically, SQLE increased the concentration of cholesterol in endothelial cells, which promoted their activation via the PI3K‐AKT signaling pathway. Moreover, NSUN2 increased the m5C modification level of SQLE and increased its stability, increasing the expression of SQLE in endothelial cells cocultured with retinal microglia isolated from diabetic mice. This study provides new perspectives on the interaction between microglia and endothelial cells involved in the pathogenesis of DR and elucidates the detailed mechanism of NSUN2‐mediated m5C modification of SQLE to regulate cholesterol metabolism and signaling pathway activation.

Establishment of a novel alloxan‐induced rabbit model exhibiting unique diabetic retinal neuropathy features assessed via <scp>ERG</scp> + <scp>VEP</scp>

2025-06-19

Xinlu Li , Xiaojing Dong , Defei Feng +7 more | Animal Models and Experimental Medicine

Abstract Background Diabetic retinal neuropathy (DRN) leads to significant visual impairment; however, no existing animal model fully replicates its neural alterations, and inconsistent induction protocols with high mortality rates hinder … Abstract Background Diabetic retinal neuropathy (DRN) leads to significant visual impairment; however, no existing animal model fully replicates its neural alterations, and inconsistent induction protocols with high mortality rates hinder long‐term investigations. Methods Adult male rabbits were randomly assigned to four experimental groups, each receiving a single intravenous injection of varying doses of alloxan and one control group. The safety and efficacy of alloxan in inducing diabetes were evaluated to determine the optimal dose. At 9 weeks following injection with alloxan, retinal function was assessed using full‐field electroretinography (ERG) and visual evoked potentials (VEPs). Retinal structure was examined in rabbits using spectral‐domain optical coherence tomography (SD‐OCT), Optos ultra‐widefield (Optos UWF) false‐color imaging, and widefield fundus fluorescein angiography (WF‐FFA). Results Rabbits in the 80 mg/kg alloxan group exhibited fewer complications, lower mortality, and a higher model success rate compared to other groups. At 9 weeks post‐injection, these rabbits demonstrated significantly elevated hemoglobin A1c and total cholesterol ( p < 0.05) relative to controls. ERG revealed statistically significant reductions in oscillatory potential and b‐wave amplitudes ( p < 0.05), while VEP indicated decreased P2 amplitude ( p < 0.001) and prolonged P2 latency ( p < 0.05). SD‐OCT, Optos UWF imaging, and WF‐FFA demonstrated no significant changes in vascular abnormalities. Additionally, Hematoxylin and Eosin staining revealed retinal swelling ( p < 0.05), and immunofluorescence confirmed glial activation and neuronal loss. Conclusions A single intravenous injection of 80 mg/kg alloxan effectively and safely induced DRN in rabbits, resulting in neural retina damage, thereby establishing this model as an ideal model for DRN research.

The influence of minor fluorophores on the detection of macular atrophy using fundus autofluorescence in patients with pathologic myopia

2025-06-19

Cristina Novarese , Guglielmo Parisi , Michele Reibaldi +1 more | Graefe s Archive for Clinical and Experimental Ophthalmology

BCAT1 Activation Reprograms Branched-Chain Amino Acid Metabolism and Epigenetically Promotes Inflammation in Diabetic Retinopathy

2025-06-18

Jingyi Wang , Zihan Yin , Jingxiao Yang +5 more | Investigative Ophthalmology & Visual Science

To investigate how branched-chain amino acid (BCAA) metabolism is remodeled and to determine its contribution to diabetic retinopathy progression. We analyzed Bcat1 and Bcat2 expression in the retina using single-cell … To investigate how branched-chain amino acid (BCAA) metabolism is remodeled and to determine its contribution to diabetic retinopathy progression. We analyzed Bcat1 and Bcat2 expression in the retina using single-cell sequencing data and immunofluorescence. Bcat1-mediated remodeling of BCAA metabolism was assessed via targeted metabolomics in Müller cells. We performed chromatin immunoprecipitation (ChIP) to examine histone methylation at inflammatory gene promoters. Additionally, we utilized RNA sequencing and kinase screening assays to delineate phosphorylation regulation of Bcat1 activity. In vivo, we established diabetic mouse models and treated them with Bcat1-specific inhibitor to evaluate retinal inflammation and vascular leakage. Bcat1 was predominantly expressed in Müller cells and exhibited increased activity under diabetic conditions, leading to a remodeling of BCAA catabolism and upregulation of inflammatory genes (interleukin 6 [Il6] and tumor necrosis factor-α [Tnf-α]). Bcat1 activity was negatively regulated by polo-like kinase 4 (Plk4)-mediated phosphorylation at threonine 333. In high glucose-treated Müller cells, elevated Bcat1 activity reduced α-ketoglutarate (α-KG), a critical substrate for histone demethylation reactions, resulting in higher histone H3 lysine 4 trimethylation (H3K4me3) levels at inflammatory gene promoters, and further boosted retinal inflammation. Treatment with chemical Bcat1 inhibitors (BAY-069 and ERG240) significantly reduced inflammatory gene expression and vascular leakage in diabetic retinas in vivo. Bcat1 activation mediates BCAA metabolism remodeling in Müller cells and epigenetically induces retinal inflammation, which offers a potential therapeutic target for diabetic retinopathy. Diabetes and diabetic retinopathy are potentially driven not only by hyperglycemia but also by dysregulated amino acid metabolism.

Prognostic factors in the treatment of polypoidal choroidal vasculopathy with conbercept: a post hoc analysis of the STAR study

2025-06-18

T H Wang , Jinfeng Qu , Ran Tang +4 more | Eye and Vision

Abstract Background A post hoc analysis of the STAR study, which was a 48-week, phase IV, multicenter randomized controlled multicenter clinical trial was performed. This study aims to identify the … Abstract Background A post hoc analysis of the STAR study, which was a 48-week, phase IV, multicenter randomized controlled multicenter clinical trial was performed. This study aims to identify the baseline factors associated with visual and anatomic changes over 48 weeks in the treatment of active polypoidal choroidal vasculopathy (PCV) with conbercept. Methods In the STAR study, 249 participants were randomized to either the 3 + Q12W (3 monthly injections followed by injections every 12 weeks) or 3 + TAE (3 monthly injections followed by treat and extend regimen) group. The association of 27 baseline factors with three outcomes—changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), and maximum retinal thickness (MRT) from baseline to 48 weeks—was investigated using univariate regression analysis followed by multivariate linear regression analysis. Results The final multivariate model indicated that worse baseline BCVA ( P < 0.01), CRT ≤ 400 μm ( P < 0.01), fewer polypoidal lesions ( P < 0.01), and younger age at baseline ( P = 0.04) were associated with greater BCVA gain at week 48. Higher CRT and MRT at baseline were associated with a greater reduction in CRT and MRT at week 48, separately ( P < 0.01 and P < 0.01, respectively). Smaller pigment epithelial detachment (PED) volume at baseline was associated with greater reductions in CRT and MRT at week 48 (both P < 0.01). Eyes with relatively good BCVA (> 73 letters) at baseline exhibited lower reductions in CRT and MRT at week 48 ( P < 0.01 and P = 0.02, respectively). At week 48, eyes with hemorrhagic PEDs showed greater reductions in CRT and MRT than those with fibrovascular PEDs ( P = 0.02 and P = 0.03, respectively). Furthermore, eyes with shallow irregular or sharp-peaked PEDs exhibited greater reductions in CRT (both P < 0.01) and MRT ( P = 0.01 and P < 0.01, respectively) than those with multilobular PEDs from baseline to week 48. Conclusions In Chinese patients with PCV receiving intravitreal injections of conbercept, baseline characteristics, including age, BCVA, CRT, MRT, number of polypoidal lesions, PED volume, and PED types and morphology, served as predictors of visual and anatomical changes over 48 weeks.

Association of wearable device-measured physical activity with full-course diabetic retinopathy and retinal traits: insights from the middle-aged and older adult cohort

2025-06-18

Chongrong Shen , Zijing Du , Chunran Lai +7 more | Diabetology & Metabolic Syndrome

To assess accelerometer-measured physical activity (PA) in patients with all stages of diabetic retinopathy (DR) and investigate its association with specific retinal structural metrics. This extensive cohort study included 13,600 … To assess accelerometer-measured physical activity (PA) in patients with all stages of diabetic retinopathy (DR) and investigate its association with specific retinal structural metrics. This extensive cohort study included 13,600 participants with an average age of 56.39 years. These subjects were divided into four groups: non-diabetes mellitus, prediabetes mellitus (Pre-DM), diabetes mellitus (DM) without DR, and DR. We evaluated multivariate-adjusted associations of PA with DR progression using logistic regression and with retinal sublayer thickness using hierarchical linear model (HLM). The mediating role of body mass index (BMI) was tested to investigate the true association between PA and the full spectrum DR. As DR progressed, the durations of moderate-intensity PA (MPA) and moderate-vigorous PA (MVPA) decreased significantly by 29% (odds ratio (OR) = 0.71, 95% CI = 0.57-0.90) to 78% (OR = 0.22, 95% CI = 0.14-0.35) and 21% (OR = 0.79, 95% CI = 0.71-0.89) to 55% (OR = 0.45, 95% CI = 0.30-0.67), respectively. Morning MPA and MVPA (6:00-12:00) were protective factors against DR, whereas late-night PA (0:00-5:59) heightened DR risk. The multivariate-adjusted linear interaction model revealed that the positive effect of MPA and MVPA on the thickness of ganglion cell-inner plexiform layer (GCIPL), macular thickness (MT), and inner nuclear layer-external limiting membrane was significantly associated with DR disease status (interaction P < 0.05). Higher MPA and MVPA were correlated with accelerated thickening rates of the GCIPL and MT sublayers, ranging from Pre-DM to those with established DR. 35.7% and 58.7% of the associations between MPA, MVPA, and the full spectrum DR were mediated by lower BMI, respectively. The diminution of PA is associated with the progression of DR and the attenuation of retinal sublayer thickness, and our findings support current PA recommendations promoting interventions to decelerate DR progression and preserve retinal health.

Limited progression of nuclear sclerosis after lens sparing vitrectomy in proliferative diabetic retinopathy eyes: a real-world investigation with Scheimpflug lens densitometry

2025-06-18

Luca Mautone , Patrick Fisel , Vasyl Druchkiv +4 more | Ophthalmologica

Background: To objectively investigate the progression of lens nuclear sclerosis after lens spearing pars plana vitrectomy (PPV) in patients with proliferative diabetic retinopathy (PDR). Methods: Comparison of Pentacam HR® Scheimpflug … Background: To objectively investigate the progression of lens nuclear sclerosis after lens spearing pars plana vitrectomy (PPV) in patients with proliferative diabetic retinopathy (PDR). Methods: Comparison of Pentacam HR® Scheimpflug imaging-based lens densitometry of eyes with PDR-associated tractive retinal detachment (Study Group) and nondiabetic eyes with rhegmatogenous retinal detachment (Control Group) after lens-sparing PPV.rp Results: Fifty-nine eyes of 55 subjects treated with gas (GT; 29 eyes in the Study and 30 in the control group; Mean follow-up: 381.41 [±309.17] days) and 42 eyes of 41 subjects treated with silicone oil tamponade (SOT; 10 eyes in the Study and 32 in the control group; mean follow-up: 326.50 [±239.59] days) were included. The prediction model for postoperative lens densitometry progression indicated that the increase in lens densitometry was lower in the study group than in the control group, regardless of the type of tamponade used. A second adjusted prediction model, including only age and baseline lens densitometry-matched eyes, further confirmed that the study group experienced a lower increase in lens densitometry in both SOT and GT cases than the control group. Conclusions: The increase in lens nuclear sclerosis is more pronounced in nondiabetic eyes than in those with PDR after lens-sparing vitrectomy. These findings support the hypothesis that ischemia in PDR may protect against the development of nuclear cataracts following PPV.

Changes in various ocular parameters of patients undergoing hemodialysis

2025-06-18

Aseem Kumar , Vijaya Sahu , Somen Misra +3 more | European Journal of Ophthalmology

Purpose To assess the alterations in various ocular parameters in patients undergoing hemodialysis. Design Prospective, observational study. Methods The study included 113 eyes from 113 patients who underwent hemodialysis due … Purpose To assess the alterations in various ocular parameters in patients undergoing hemodialysis. Design Prospective, observational study. Methods The study included 113 eyes from 113 patients who underwent hemodialysis due to chronic kidney disease and acute kidney injury between January 2021 and August 2022. All participants underwent complete ophthalmic exam which included best corrected visual acuity (BCVA), slit lamp examination, intraocular pressure (IOP) measurement and dilated examination using slit lamp biomicroscope and indirect ophthalmoscope. Optical coherence tomography (OCT) was done for all patients before they underwent hemodialysis and central subfield thickness (CST), retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness were assessed. The ophthalmic exam and OCT scan were repeated within 1–2 h of hemodialysis. Results The mean age (+/- SD) of the study population was 42.14 ± 13.25 years, with 65.5% males. Most participants were aged 41–60 years. BCVA and IOP did not change significantly after hemodialysis ( p = 0.74 and p = 0.37, respectively). Retinal parameters showed significant changes, with decreased CST ( p < 0.001) and GCC thickness ( p = 0.04). There was no significant change in RNFL thickness ( p = 0.44). CST positively correlated with dialysate flow rate and negatively with blood flow rate. A weak correlation was found between GCC thickness and ultrafiltration and dialysate flow rate. Conclusion Hemodialysis causes alterations in retinal parameters with a decrease in the CST and GCC thickness.

Quantifying Effects of Lifestyle Changes on Progression to Advanced Age-Related Macular Degeneration in High Genetic Risk Individuals

2025-06-18

Johanna M. Seddon , Dikha De , Bernard Rosner | medRxiv (Cold Spring Harbor Laboratory)

We examined the extent to which adopting healthy lifestyle behaviors could offset high genetic risk for progression to advanced age-related macular degeneration (AMD), to address concerns of family members of … We examined the extent to which adopting healthy lifestyle behaviors could offset high genetic risk for progression to advanced age-related macular degeneration (AMD), to address concerns of family members of affected patients. Prospective longitudinal study. Eyes with early or intermediate AMD at baseline were defined based on the Age-Related Eye Disease Study severity scale. High genetic risk was defined as the third tertile of a genetic risk score for progression, adjusted for age, race and sex. Information on lifestyle behaviors was obtained from baseline risk and food frequency questionnaires. Risk-inducing and health-promoting lifestyle profiles were defined based on dichotomous categorizations of smoking, body-mass index (BMI), and dietary caloric intake, green leafy vegetables and fish, in never and ever smokers. Cox proportional hazard ratios (HRs), relative risks (RRs) and population attributable risks (PARs) were calculated, adjusting for inter-eye correlation, demographic factors, macular status and family history. Progression to advanced AMD (AAMD) and subtypes geographic atrophy (GA) and neovascular (NV), confirmed at 2 consecutive visits over 5 years of follow-up. Among 898 high genetic risk eyes, 207 eyes progressed to AAMD (23%). Among never smokers, a high risk-inducing lifestyle profile conferred a 3-fold increased incidence of AAMD, compared to an ideal health-promoting lifestyle profile [HR = 3.3 (CI 1.8, 6.4), P <0.001]. In ever smokers, a risk-inducing profile was independently associated with a 5-fold increased incidence of AAMD [HR = 5.3 (CI 2.3,11.9), P <0.001]. Stronger effects of these lifestyle behaviors were seen for GA compared to NV. Estimated PARs suggested adopting an ideal health-promoting profile could prevent 56% of incident AAMD in never smokers and 60% in ever smokers. Unhealthy behaviors increased incidence of AAMD by 3 to 5-fold among a highly genetically susceptible population, and 56-60% of AAMD incidence was attributed to the modifiable factors of smoking, high BMI, high caloric intake and low intake of foods rich in lutein-zeaxanthin and omega-3 fatty acids. These results underscore the importance of lifestyle interventions even in high genetic risk populations, such as relatives of affected patients, to reduce progression from early and intermediate AMD to advanced vision-threatening stages.

Effectiveness of dynamic phototherapy in the management of telangiectatic capillaries: A case series

2025-06-18

Alexandre Moulin , Lucas Séjournet , Thibaud Mathis +1 more | European Journal of Ophthalmology

Purpose Telangiectatic capillaries (TelCaps) are large capillary microaneurysms that can be found in diabetic patients. Focal laser photocoagulation is the standard treatment for these lesions. In case of a lesion … Purpose Telangiectatic capillaries (TelCaps) are large capillary microaneurysms that can be found in diabetic patients. Focal laser photocoagulation is the standard treatment for these lesions. In case of a lesion too close to the fovea, there is a risk of central scotoma and conventional laser should not be used. In this case, dynamic phototherapy (PDT) can be discussed. Case report Two patients with perifoveal TelCaps associated with diabetic macular edema were treated with PDT. There was persistent central macular edema in spite of a well-executed treatment with intravitreal injections (IVT). Both visual acuity and central macular thickness improved after PDT. This therapy seems to be a possible option in the absence of another therapeutic solution for the treatment of perifoveal TelCaps with promising results should be noted despite the difficulty accessibility to Verteporfin. Conclusion The management of perifoveal TelCaps is complex due to their impact on visual acuity, the therapeutic burden for patients, as well as the potential complications associated with focal laser. In the absence of other therapeutic options, the use of PDT may prove relevant in this indication.

Prognostic factors of conbercept intravitreal injection in the treatment of choroidal neovascularization secondary to pathologic myopia

2025-06-18

Yeqiang Shi , Hui Yao , Peng Zhang +2 more | European Journal of Ophthalmology

Purpose Choroidal neovascularization secondary to pathologic myopia (PM-CNV) is an important main factor leading to decreased vision in patients with pathologic myopia. Conbercept, an anti-VEGF drug, is currently the primary … Purpose Choroidal neovascularization secondary to pathologic myopia (PM-CNV) is an important main factor leading to decreased vision in patients with pathologic myopia. Conbercept, an anti-VEGF drug, is currently the primary treatment for PM-CNV. This study used optical coherence tomography angiography (OCTA) data to investigate the factors influencing the visual prognosis of patients with PM-CNV. Methods Data from patients with PM-CNV diagnosed in the Department of Ophthalmology of The Second People's Hospital of Jinan City from January 2019 to December 2022 were retrospectively analyzed. All patients received intravitreal injections of 0.05 ml Conbercept (0.5 mg) following a 1 + pro re nata (PRN) regimen. Patients were divided into two groups based on visual acuity at 12 months after treatment: improved (best-corrected visual acuity [BCVA] improvement > 1 line) and non-improved (BCVA improvement ≤ 1 line or reduced visual acuity). The factors BCVA after treatment were analyzed using logistic regression analysis. Results Twelve months after treatment, there were 77 patients in the improved group and 23 in the non-improved group. Multivariable logistic regression analysis revealed that age (odds ratio (OR) = 1.303, 95% confidence interval (CI): 1.059–1.603, P = 0.012), baseline BCVA (OR = 15.939, 95% CI: 2.490–102.013, P = 0.003), subfoveal CNV (OR = 0.055, 95% CI: 0.010–0.312, P = 0.001), and well-organized CNV (OR = 0.049, 95% CI: 0.009–0.276, P = 0.001) were independently associated with the efficacy of intravitreal injection of conbercept in patients with PM-CNV. Conclusion Poor postoperative BCVA recovery in patients with PM-CNV after conbercept intravitreal injection could be associated with age, baseline BCVA, and location and morphology of CNV.

Fenofibrate Exerts Protective Effects in Diabetic Retinopathy

2025-06-18

Shimei Chen , Xiaoqian Wang , Dandan Sun +5 more | Current Eye Research

This study examines the protective effects of fenofibrate on retinal health in diabetic retinopathy, focusing on its ability to reduce inflammation, oxidative stress, and restore autophagy while preventing ferroptosis. Using … This study examines the protective effects of fenofibrate on retinal health in diabetic retinopathy, focusing on its ability to reduce inflammation, oxidative stress, and restore autophagy while preventing ferroptosis. Using a streptozotocin (STZ)-induced diabetic rat model and cultured ARPE-19 cells under high glucose conditions, we assessed the impact of fenofibrate on oxidative stress markers, autophagy-related proteins, and tight junction integrity. Fenofibrate's role in modulating inflammation and preventing ferroptosis was also evaluated. Fenofibrate treatment reduced ROS production and NADPH oxidase activity, alleviating oxidative stress in retinal tissues. Additionally, fenofibrate enhanced autophagy, as indicated by increased LC3 expression, and maintained tight junction protein expression. These effects contributed to the stabilization of cellular homeostasis, potentially slowing disease progression. Fenofibrate offers significant protective effects in diabetic retinopathy by reducing inflammation and oxidative stress, promoting autophagy, and inhibiting ferroptosis, making it a promising therapeutic option for managing the disease.

Development and optimisation of esculin-loaded chitosan microspheres for intravitreal injection

2025-06-17

Ning He , Danqing Wu , Rui Luo +5 more | Journal of Microencapsulation

This study was to prepare the esculin-loaded chitosan microspheres for intravitreal injection and explore the feasibility of the treatment of macular degeneration. The microspheres were fabricated using an emulsification crosslinking … This study was to prepare the esculin-loaded chitosan microspheres for intravitreal injection and explore the feasibility of the treatment of macular degeneration. The microspheres were fabricated using an emulsification crosslinking technique. The drug loading, encapsulation efficiency, and mean particle diameter of the optimised esculin-loaded chitosan microspheres were 8.03 ± 1.30%, 93.03 ± 2.16%, and 4.81 ± 1.60 μm, respectively. The thermal stability evaluation at 25 °C demonstrated consistent particle diameter maintenance, with microspheres retaining sizes of 4.73 ± 1.75 μm and 4.89 ± 1.55 μm after 15 and 30 days' storage periods, respectively. The in vitro release profile demonstrated 80% cumulative drug release from the microspheres over a 72 h period. Subsequent pharmacokinetic analysis revealed significantly enhanced parameters in the vitreous humour following intravitreal administration, with the half-life (t1/2) reaching 879.88 ± 44.00 min and the area under curve (AUC) attaining 150.18 ± 2.28 × 103 mg·min/mL. Intravitreal injection of esculin-loaded chitosan microspheres offers a promising drug delivery system for the treatment of macular degeneration.

Clinical Trials of Aflibercept Biosimilars: A Review

2025-06-17

Hyun-Woo Lee , Ashish Sharma , Se Joon Woo | Journal of Ocular Pharmacology and Therapeutics

Anti-vascular endothelial growth factor (VEGF) biologics have revolutionized the management of VEGF-driven retinal diseases, significantly improving visual outcomes for patients. Following the patent expiration of ranibizumab, multiple anti-VEGF biosimilars have … Anti-vascular endothelial growth factor (VEGF) biologics have revolutionized the management of VEGF-driven retinal diseases, significantly improving visual outcomes for patients. Following the patent expiration of ranibizumab, multiple anti-VEGF biosimilars have been developed, with the first approved for ophthalmic use entering the market in 2022. More recently, the expiration of aflibercept market exclusivity in 2024 has led to the rapid development of aflibercept biosimilars-some already approved and others pending regulatory decisions. By offering clinically equivalent and cost-effective alternatives to reference biologics, biosimilars can lessen financial burdens and improve treatment adherence. Understanding the study designs of biosimilars can mitigate negative perceptions of biosimilars and promote their active implementation. In this review, we provide a comprehensive comparison of the designs of phase III clinical trials of aflibercept biosimilars, including recently published results.

MORPHOLOGICAL FEATURES OF MACULAR EDEMA IN POST-THROMBOTIC AND DIABETIC RETINOPATHY BASED ON OPTICAL COHERENCE TOMOGRAPHY FINDINGS

2025-06-17

M.K. Karimova , S. A. Djamalova , Z.A. Mahmudova | Azerbaijan Journal of Ophthalmology

Purpose – to identify and comparatively characterize the morphological features of macular edema in patients with post-thrombotic retinopathy and diabetic macular edema (DME) based on optical coherence tomography (OCT) findings. … Purpose – to identify and comparatively characterize the morphological features of macular edema in patients with post-thrombotic retinopathy and diabetic macular edema (DME) based on optical coherence tomography (OCT) findings. Material and methods This study included 60 patients (60 eyes) with significant ME, divided into two groups: 28 patients with retinal vein occlusion (RVO) and 32 patients with DME. All patients underwent comprehensive ophthalmologic examination, including spectral-domain OCT of the macular region. The average duration of the process before inclusion in the study was 6.3±1.4 months in the RVO group and 5.7±1.2 months in the DMO group. The following parameters were assessed: central retinal thickness, presence of cystoid changes, subretinal fluid, hyperreflective foci, disorganization of the retinal inner layers (DRIL), and choroidal thickness measured in the subfoveal, nasal, and temporal areas. Results Patients with DME demonstrated greater central retinal thickness compared to those with RVO (p=0.043). Subretinal fluid was more frequently observed in the RVO group (p=0.027). Choroidal thickness was significantly greater in patients with RVO across all measured areas (p<0.01). Conclusion ME in post-thrombotic retinopathy and DR exhibits distinct morphological haracteristics. Identifying these differences is crucial for improving diagnostic accuracy and selecting individualized therapeutic strategies. Key words: macular edema, retinal vein occlusion, diabetic retinopathy, optical coherence tomography, choroid

THE SIGNIFICANCE OF MULTIFOCAL ELECTRORETINOGRAPHY IN PREDICTING TREATMENT OUTCOMES FOR DIFFERENT FORMS OF DIABETIC MACULAR EDEMA

2025-06-17

N.А. Shahbazova , M. Karimov | Azerbaijan Journal of Ophthalmology

Purpose – to predict treatment outcomes in different forms of diabetic macular edema (DME) using multifocal electroretinography (mf-ERG). Material and methods The study included 82 patients divided into two groups: … Purpose – to predict treatment outcomes in different forms of diabetic macular edema (DME) using multifocal electroretinography (mf-ERG). Material and methods The study included 82 patients divided into two groups: Group I – 41 patients with cystoid macular edema (41 eyes); group II – 41 patients with tractional macular edema (41 eyes). The patients included 49 males (59.8%) and 33 females (40.2%), with a mean age of 58.46 ± 8.11 years (min: 26, max: 77 years). The known duration of diabetes mellitus (DM) was 13.41 ± 7.07 years (min: 0, max: 31 years). All examined patients were confirmed to have various types of DME. Patients with cystoid macular edema were treated with anti-VEGF injections into the vitreous body, while those with tractional macular edema (41 eyes) underwent pars plana vitrectomy (41 patients). All patients underwent mf-ERG before and after treatment. Results Mf-ERG was shown to predict the functional outcomes of DME treatment based on P1 amplitude indicators. In cystoid macular edema, the predictive power of the P1 amplitude indicator in the first ring before treatment for post-treatment visual acuity was 58.0% (regression coefficient -0.021, p<0.001), while in tractional macular edema, the predictive power of the P1 indicator in the first ring before surgery for post-surgical visual acuity was 70.3% (regression coefficient -0.026, p<0.001). Conclusion The results of this study demonstrate that functional indicators obtained from mf-ERG are related to the final visual prognosis and confirm the value of mf-ERG in predicting functional outcomes of DME treatment. Key words: diabetic retinopathy, macular edema, vitreomacular traction, multifocal electroretinography

Embossing enhances visualization of retinal pigment epithelium alterations in fundus autofluorescence in central serous chorioretinopathy

2025-06-16

Elham Sadeghi , Nicola Valsecchi , Arman Zarnegar +5 more | European Journal of Ophthalmology

Purpose Central serous chorioretinopathy (CSCR) demonstrates retinal pigment epithelium (RPE) alterations visible on fundus autofluorescence (FAF). Embossing is an image processing technique that replaces pixels with a shadow or a … Purpose Central serous chorioretinopathy (CSCR) demonstrates retinal pigment epithelium (RPE) alterations visible on fundus autofluorescence (FAF). Embossing is an image processing technique that replaces pixels with a shadow or a highlight, improving image visualization. We explored how embossing improves the delineation of altered RPE areas in eyes with chronic CSCR on blue-FAF images. Methods This study includes 52 eyes of 40 patients with chronic CSCR. Images were embossed with a coefficient of 0.5. The area of RPE alteration was assessed by two masked, double-blinded observers using ImageJ Fiji software. Accuracy was assessed based on inter-rater reliability (ICC) and compared before and after embossing using Fisher's z-transformation. Results The mean age of the study patients was 53.02 ± 12.87 years. The RPE alteration area measurements by the first observer for the pre-embossed images was 12.1 ± 13.1 mm2, and for the post-embossed images was 11.9 ± 13.4 mm2 ( P = 0.7). The RPE alteration area measurements by the second observer for the pre-embossed images was 11.3 ± 13.3 mm2, and for the post-embossed images was 10.3 ± 12.8 mm2 ( P = 0.5). The mean area for both observers in the pre-embossed images was 11.7 ± 12.8 mm2, and in the post-embossed images was 11.1 ± 13.0 mm2 ( P = 0.217). The ICC in the pre-embossed images between two observers was 0.931 (CI 0.879–0.960), which increased to 0.983 (CI 0.970–0.990) in post-embossed images ( P < 0.001). Conclusions Embossing FAF images can enhance the visibility of RPE alterations in CSCR, allowing for better delineation of borders, which improves accuracy.

Interventions for central serous chorioretinopathy: a network meta-analysis

2025-06-16

Clemens AK Lange , Riaz Qureshı , Laurenz Pauleikhoff | Cochrane library

Correlation of retinal thickness, macular volume, and their fluctuation with visual outcomes in patients with macular edema due to retinal vein occlusion

2025-06-16

Kwanchanok Rattanalert , Patama Bhurayanontachai , Mansing Ratanasukon +2 more | International Journal of Retina and Vitreous

Abstract Background This study aimed to examine the utility of macular volume (MV), central retinal thickness (CRT), and their fluctuations for predicting post-treatment visual acuity in patients with macular edema … Abstract Background This study aimed to examine the utility of macular volume (MV), central retinal thickness (CRT), and their fluctuations for predicting post-treatment visual acuity in patients with macular edema (ME) secondary to retinal vein occlusion (RVO). Methods This retrospective cohort study included patients treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for ME due to RVO at a tertiary university hospital between August 2016 and July 2020. We identify the correlation of the MV, CRT, with their fluctuations, and best-corrected visual acuity (BCVA) measured using optical coherence tomography at baseline and at 1-, 3-, 6-, and 12-months post-treatment. Results Among the 74 eyes included, 27 and 47 had central RVO (CRVO) and branch RVO (BRVO), respectively. Following anti-VEGF therapy both, the CRVO and BRVO group exhibited significant improvements in BCVA, CRT, and MV compared to baseline. In all patients, MV was consistently correlated with BCVA, whereas CRT was correlated with BCVA at selected time points. In patients with CRVO, MV was a better predictor of post-treatment visual outcomes than CRT. Moreover, fluctuations in CRT and MV correlated with BCVA over 12 months. Conclusions MV yielded more correlation with visual outcomes in patients with RVO and ME receiving anti-VEGF therapy than CRT. Considering concurrent MV and CRT measurements could enhance more precision of treatment assessment, especially in CRVO patients.

Real-World 5-Year Outcomes of Age-Related Macular Degeneration with Bevacizumab as First-Line Anti-VEGF

2025-06-15

Haras Mhmud , Jeroen Vermeulen , Odette A. M. Tigchelaar-Besling +5 more | Ophthalmology and Therapy

To evaluate long-term outcomes of anti-VEGF therapy for neovascular age-related macular degeneration (nAMD) in the Netherlands (NL), where bevacizumab is the mandated first-line drug, compared to high-income countries using ranibizumab … To evaluate long-term outcomes of anti-VEGF therapy for neovascular age-related macular degeneration (nAMD) in the Netherlands (NL), where bevacizumab is the mandated first-line drug, compared to high-income countries using ranibizumab or aflibercept as initial treatments. Five-year data from the Fight Retinal Blindness! (FRB) registry, a real-world prospective registry, were analyzed. Outcomes from 1473 Dutch eyes (1229 patients) treated with bevacizumab were compared with 7144 eyes (5884 patients) in a reference group (RG) from 13 socioeconomically similar countries. The primary outcome was mean visual acuity (VA) at yearly intervals; secondary outcomes included injection frequency and switching rates to alternative anti-VEGF agents. Throughout the 60 months, mean VA was consistently higher in Dutch eyes (baseline: NL 60.2 vs. RG 59.2; 60 months: NL 64.9 vs. RG 62.6). The Dutch group cumulatively received 14.5 more injections over 5 years and had a higher rate of switching (70.9% vs. 50.9%) with a shorter median time to switching (11.9 months vs. 17.7 months). Patients treated in Dutch FRB! clinics have good long-term outcomes with a 2.3-letter higher mean VA at the 60-month timepoint compared to FRB! clinics in the RG. The Dutch patients, who began treatment with bevacizumab, received 14.5 more injections over 5 years and had a 40% higher rate of switching to an alternative drug, with switching occurring 5.8 months earlier. This study highlights the benefits of early and more intensive management to optimize visual outcomes, which appear more important than the choice and price of the first-line drug.

Age-independent anti-angiogenic therapy for choroidal neovascularization by targeting secretogranin III

2025-06-15

Chengchi Huang , Hong Tian , Wei Li | GeroScience

Effect of disease duration on foveal microvasculature assessed by OCTA in type 2 diabetes mellitus without clinical diabetic retinopathy

2025-06-15

David Leonardo Cruvinel Isaac , Alexandre Caiado Ferreira Pires , Lucio Pereira Neves +7 more | International Journal of Retina and Vitreous

Abstract Background The objective of this study was to establish a comparison between the vessel density (VD) and foveal avascular zone (FAZ) of patients with type 2 diabetes mellitus (T2DM) … Abstract Background The objective of this study was to establish a comparison between the vessel density (VD) and foveal avascular zone (FAZ) of patients with type 2 diabetes mellitus (T2DM) who lacked clinical signs of diabetic retinopathy (DR) and non-diabetic patients using optical coherence tomography angiography (OCTA). Methods A cross-sectional comparative case-control study (unpaired) was carried out at two tertiary hospitals. All subjects underwent optical coherence tomography angiography (OCTA) examination (DRI OCT Triton Swept Source, Topcon, Japan). The average VD in the superficial capillary plexus (SCP) and the deep capillary plexus (DCP), the FAZ area (mm2) in SCP, and DCP were taken into analysis. The time since the diagnosis of T2DM was used to stratify patients with diabetes between 5 and 10 years and those with a diagnosis of more than 10 years. Results Compared to non-diabetic controls, the parafoveal VD in both SCP and DCP was significantly reduced in the eyes of T2DM patients without clinical DR ( p < 0.001). Additionally, the VD was also statistically reduced in T2DM diagnosed more than 10 years ago compared to T2DM cases diagnosed between 5 and 10 years ago ( p < 0.001). The FAZ area in both plexuses was larger in T2DM eyes compared to controls ( p < 0.001). The FAZ area was enlarged in DCP ( p = 0.04), but there was no significance of FAZ area in SCP when comparing patients with T2DM diagnosed between 5 and 10 years ago to those diagnosed more than 10 years ago ( p = 0.06). Conclusion In diabetic patients with long-term diagnosed disease, OCTA was shown to be capable of detecting preclinical microvascular foveal abnormalities prior to the development of clinically apparent retinopathy. According to our findings, OCTA has the potential to be a promising instrument for the early detection of vascular micro-abnormalities and the routine screening of diabetic eyes.

Reduction in choroidal thickness associated with the progression of pachychoroid spectrum diseases

2025-06-14

Hidetaka Matsumoto , Junki Hoshino , Kosuke Nakamura +3 more | Japanese Journal of Ophthalmology

Impact of type 1 diabetes on binocular vision: Evidence from a comparative analysis

2025-06-14

María Carmen Sánchez‐González , Víctor Ponce‐García , Concepción De‐Hita‐Cantalejo +2 more | Annals of the New York Academy of Sciences

Abstract Binocular vision function was assessed in individuals with type 1 diabetes (T1D) without retinopathy and compared to a control group to identify potential nonstrabismic binocular vision disorders. This cross‐sectional … Abstract Binocular vision function was assessed in individuals with type 1 diabetes (T1D) without retinopathy and compared to a control group to identify potential nonstrabismic binocular vision disorders. This cross‐sectional study included 80 participants (40 T1D, 40 controls) without systemic or ocular diseases, visual impairments, medications, or prior ocular surgery. Highly repeatable tests evaluated heterophoria, the accommodative convergence/accommodation (AC/A) ratio, near point of convergence (NPC), fusional vergences, vergence facility, and stereoacuity. Diagnosed dysfunctions included convergence insufficiency, divergence insufficiency, basic exophoria, basic esophoria, fusional vergence dysfunction, convergence excess, and divergence excess. Individuals with T1D showed significantly farther NPC (break: 5.50 vs. 3.80 cm, p = 0.005; recovery: 8.32 vs. 5.69 cm, p < 0.001), lower near positive fusional vergence (break: 20.70 Δ vs. 24.25 Δ; recovery: 11.50 Δ vs. 14.75 Δ, p = 0.02 and 0.01, respectively), reduced vergence facility (5.10 vs. 7.15 cpm, p = 0.003), and a lower AC/A ratio (3.30 vs. 4.00, p = 0.01). More participants with T1D had binocular vision parameters outside the normal range, with a higher prevalence of binocular vision disorders ( p = 0.048). These findings highlight the impact of T1D on binocular vision and emphasize the need for optometric evaluations for early detection and management.

Multimodal Treatment Outcomes in Chronic Central Serous Chorioretinopathy: A Case Study

2025-06-14

Namrata Srivastava | International Scientific Journal of Engineering and Management

Abstract Purpose: This case study evaluates the clinical progression and visual outcomes in a patient with a severe form of chronic central serous chorioretinopathy (cCSC), aiming to assess the efficacy … Abstract Purpose: This case study evaluates the clinical progression and visual outcomes in a patient with a severe form of chronic central serous chorioretinopathy (cCSC), aiming to assess the efficacy of multimodal treatments—particularly photodynamic therapy (PDT)—in managing recurrent central serous retinopathy (CSR). Insights are contextualized with recent literature from 2020–2025, including Breukink et al. (2020). Methods: A 45-year-old male with recurrent CSR was followed from 2018 to 2025 at Dr. Jawahar Lal Rohtagi Hospital, Semi-Government Allied Health & Paramedical Institute, Kanpur.. Clinical evaluation included OCT, FA, FAF, and BCVA assessments. Subretinal fluid was confirmed, with a baseline BCVA of 20/40. Management involved half-dose PDT, navigated laser photocoagulation, anti-VEGF therapy for CNV, oral eplerenone, and lifestyle modifications. Risk factors such as stress, corticosteroid use, and past smoking were addressed. Quality-of-life was monitored using the NEI-VFQ-39 questionnaire, ensuring a comprehensive and multidisciplinary approach to long-term disease management. Results: CSR relapses occurred in 2020, 2021, and 2023, progressing to cCSC with CNV. Although SRF resolved after each intervention, final BCVA declined to 20/50 due to photoreceptor loss and diffuse retinal pigment epithelium (RPE) atrophy. A NEI-VFQ-39 score of 65/100 indicated moderate visual function impairment. These findings align with Breukink et al., underscoring that anatomical resolution does not ensure visual recovery. Conclusion: Despite treatment success in SRF resolution, irreversible retinal damage may limit visual recovery in cCSC. Early, personalized, and continuous intervention is essential. Keywords: Central Serous Retinopathy, Chronic CSC, Photodynamic Therapy, Anti-VEGF, Multimodal Imaging, RPE Atrophy, Subretinal Fluid, Visual Outcomes.

Hemodynamics of the eye during combined treatment of severe proliferative diabetic retinopathy

2025-06-14

В. В. Нероев , N. V. Neroeva , T. D. Okhotsimskaya +2 more | Russian Ophthalmological Journal

Diabetic retinopathy (DR) is a severe late neuromicrovascular complication of diabetes mellitus. Panretinal laser photocoagulation is a method of choice of DR treatment; antiangiogenic therapy applies if necessary. The traction … Diabetic retinopathy (DR) is a severe late neuromicrovascular complication of diabetes mellitus. Panretinal laser photocoagulation is a method of choice of DR treatment; antiangiogenic therapy applies if necessary. The traction development, hemophthalmos, and retinal detachment are the most common complications of proliferative DR and needs vitreal surgery. Ultrasound examination with blood flow assessment and laser speckle flowography (LSFG) are very useful methods in retinal blood flow detecting. Purpose of the study: to conduct blood flow parameters using ultrasound dopplerography with assessment of blood flow and LSFG in 67-year-old patient with bilateral severe proliferative DR after panretinal photocoagulation, avitria, pseudophakia and stable ophthalmological status. Patient observed a significant decrease in retinal blood flow and normal values of choroidal blood flow, combined with rather high visual acuity. Conclusion . Choroidal blood flow plays a significant role in maintenance of visual functions. Study of eye hemodynamic status by ultrasound dopplerography and LSFG is effective in DR patients. Quantitative and qualitative blood flow control proved usefulness in clinical practice and requires further study.

Bruch’s membrane heparan sulfate retains lipoproteins in the early stages of age-related macular degeneration

2025-06-13

Christopher B. Toomey , Savanna Pflugmacher , K. Park +7 more | Proceedings of the National Academy of Sciences

Lipoprotein retention in Bruch’s membrane is a key event in the pathobiology of early and intermediate age-related macular degeneration (AMD). However, the mechanism of lipoprotein retention in BrM is unknown. … Lipoprotein retention in Bruch’s membrane is a key event in the pathobiology of early and intermediate age-related macular degeneration (AMD). However, the mechanism of lipoprotein retention in BrM is unknown. Given the established role of glycosaminoglycans (GAG) in binding lipoproteins, our laboratory sought to determine the role of GAGs in AMD BrM. In this study, BrM GAG content in AMD pathobiology was analyzed in human postmortem tissue. Strikingly, increased levels of highly sulfated heparan sulfate were present in AMD Bruch’s membrane as compared to non-AMD samples. In addition, using scanning electron microscopy of postmortem AMD tissue, we show aggregates of lipoprotein-like particles on the retinal pigmented epithelium side of Bruch’s membrane adjacent to heparan sulfate. We also show that heparin displaces lipoproteins rich in apolipoprotein A1 from human BrM, suggesting their identity as high-density lipoproteins. Using human BrM immobilized to quartz crystal microbalance biosensor (QCM) chips, we show that heparan sulfate is required for lipoprotein binding to BrM and soluble heparan sulfate can remove lipoproteins bound to BrM. Thus, our data establish that heparan sulfate regulates lipoprotein deposition in AMD BrM. These findings provide a foundation for targeted therapies capable of either preventing lipoprotein accumulation or removing drusen in the early and intermediate stages of AMD prior to vision loss.

Macular Degeneration Improvement with QIAPI 1™. Case Report

2025-06-13

Arturo Solís Herrera | Biomedical Journal of Scientific & Technical Research