Age-related Macular Degeneration Group Research Articles

Evaluation of choroid vascular layer thickness in wet age-related macular degeneration using artificial intelligence

To facilitate the assessment of choroid vascular layer thickness in patients with wet age-related macular degeneration (AMD) using artificial intelligence (AI). We included 194 patients with wet AMD and 225 healthy participants. Choroid images were obtained using swept-source optical coherence tomography. The average Sattler layer-choriocapillaris complex thickness (SLCCT), Haller layer thickness (HLT), and choroidal thickness (CT) were auto-measured at 7 regions centered around the foveola using AI and subsequently compared between the 2 groups. The SLCCT was lower in the AMD group than in the control group (P<0.05). The HLT was significantly higher in the AMD group than in the control group at the Tparafovea and T-perifovea in the total population (P<0.05) and in the ≤70-year subgroup (P<0.05). The CT was higher in the AMD group than in the control group, particularly at the N-perifovea, T-perifovea, and T-parafovea in the ≤70-year subgroup; Interestingly, it was lower in the AMD group than in the control group at the Nparafovea, N-fovea, foveola, and T-fovea in the >70-year subgroup (P<0.05). This novel AI-based auto-measurement was more accurate, efficient, and detailed than manual measurements. SLCCT thinning was observed in wet AMD; however, CT changes depended on the interaction between HLT compensatory thickening and SLCCT thinning.

Evaluation of the Effect of Age-Related Macular Degeneration Type And Stage on the Risk of Parkinson’s Disease

The aim of the study was to investigate the distance between Parkinson's Disease (PD) and Age-Related Macular Degeneration (AMD) type and stage.. Our prospective study, the dry-type AMD group consisted of 296 patients with early and 284 patients with late-stage. The neovascular AMD group included 285 early and 277 late-stage patients. The control group consisted of 300 patients. AMD patients were grouped as dry and neovascular type and early and late stage. The patients were questioned about the use of drugs for PD, and the use was recorded as having the disease. If any of the complaints seen in the PD were present, the patient was referred to a neurologist. PD was detected in 1% of the control group and 4.6% in the neovascular type AMD group, and this difference was significant (p:0.04). This difference was present in both the early (%4.5) and late-stage (%4.6 ) (p:0.04, p:0.04). PD was determined 3.78 times greater among neovascular AMD patients(p:0.03), and significant association was present in both early (3.72 times) and late-stage (3.82 times) (p:0.03, p:0.03). In the dry-type AMD group 2.7% PD was detected and there was no statistical difference (p&amp;gt;0.05). This difference was not significant in the early stage (%2.3) or late-stage (%2.8) and also there was no association with dry-type AMD (p&amp;gt;0.05). Also, unilateral and bilateral involvement in AMD was not associated with PD (p&amp;gt;0.05). Our study revealed the association between both early and late neovascular AMD and PD. However, any significant relationship was not detected in terms of both unilateral and bilateral involvement.

Examining the correlation of lymphangiogenesis biomarkers with clinical condition in Age-Related Macular Degeneration (AMD)

The aim of this study is to investigate the relationship between age-related macular degeneration (AMD) and lymphangiogenesis biomarkers, namely LYVE-1, Podoplanin, VEGF-C, VEGFR-2 and VEGFR-3. This prospective and interventional study includes 30 patients with AMD which may be dry or wet type and 30 controls for whom vitrectomy and phacoemulsification was indicated due to additional pathologies (epiretinal membrane, macular hole, retinal detachment, and cataract). 0.1–0,2 ml of aqueous humor and 0.5–1 ml of vitreous sample was taken during the operations. Before the operations 1 tube serum was also taken. All the lymphangiogenesis biomarkers in the study are examined by ELISA method. LYVE-1 (p = 0.001) and Podoplanin (p = 0.004) levels in the vitreous for the patient group are found to be significantly lower than the control group. Serum (p = 0.019), vitreous (p = 0.001), aqueous (p < 0.001) levels of VEGF-C for the patient group are significantly higher than the control group. VEGF-C/VEGFR-2 (p < 0.001), VEGF-C/VEGFR-3 (p < 0.001) ratios in the vitreous for the patient group are found to be significantly higher than the control group. Especially in wet AMD patients, LYVE-1 level is significantly lower in the vitreous (p = 0.002) and aqueous (p = 0.002) than the control group. In addition, Podoplanin level is observed as significantly lower in the vitreous (p = 0.014) and serum (p = 0.002) in comparison to control group. In the wet AMD group, VEGF-C level in the vitreous (p < 0.001), aqueous (p < 0.001) and serum (p = 0.001) is higher than the control group. The result of this study indicates a valid relationship between the weakening of lymphangiogenesis and the pathophysiology of AMD, especially for the wet type. It is observed that the levels of receptors that bind VEGF-C (VEGFR-2 and VEGFR-3) do not increase at the same rate as VEGF-C to compensate for the increase in VEGF-C. The absence of an increase in VEGFR-3, which is especially necessary for lymphangiogenesis, also suggests that lymphangiogenesis is weakened or decreased in AMD. In the future interventional studies with larger series, examination of lymphangiogenic biomarkers in inflammatory retinal diseases and glaucoma may reveal unexplored details.

Visual Outcome of Non-traumatic Dense Vitreous Hemorrhage in Patients without Diabetes: Single Center Case Series.

Dense vitreous hemorrhage is a vision-threatening disease with varied clinical manifestations. Herein, we aimed to evaluate its causes and outcomes in patients without diabetes. A retrospective cohort including 60 eyes from 60 patients with an initial diagnosis of non-traumatic fundus-obscuring dense vitreous hemorrhages and without diabetes was recruited. The relevant medical records from January 2013 to December 2019 were reviewed and analyzed. We classified patients into the following four groups, depending on the underlying cause of dense vitreous hemorrhage: eight cases in the age-related macular degeneration (AMD) group, four cases in the posterior vitreous detachment group, 20 cases in the Tear group, and 28 cases in the Vascular group. The most common cause of dense vitreous hemorrhage was retinal vascular obstructive disease (46.7%); the AMD group showed the worst prognosis. The extent of best corrected visual acuity change was significantly better in patients who underwent vitrectomy compared to those receiving conservative treatment; best corrected visual acuity change (logMAR) was 1.62±0.57 and 1.06±0.88 in the surgical and non-surgical groups, respectively (p=0.007, Student t-test). Retinal vascular disease is the most common cause of vitreous hemorrhages, and surgical treatments have a better visual outcome than non-surgical treatments.

Alterations of the Ganglion Cell Complex in Age-Related Macular Degeneration: an AMISH Eye Study Analysis

To compare the Ganglion Cell Complex (GCC) thickness in eyes with age-related macular degeneration (AMD) versus healthy controls in an elderly Amish population DESIGN: Cross-sectional study METHODS: This is a post hoc analysis of the family-based prospective study of Amish subjects. Study subjects were imaged by the Cirrus HD-OCT (Carl Zeiss Meditec Inc, Dublin, CA) using a macular cube protocol of 512 × 128 scans (128 horizontal B-scans, each compromising 512 A-scans) over a 6 mm x 6 mm region centered on the fovea. The ganglion cell analysis algorithm calculated the GCC thickness by segmenting the outer boundaries of the retinal nerve fiber layer (RNFL) and inner plexiform layer (IPL) in all B-scans of the volume, with the region between these boundaries representing the combined thickness of the GCL and the IPL layer. A number of parameters were used to evaluate the GCC thickness: the average GCC thickness, minimum (lowest GCC thickness at a single meridian crossing the elliptical annulus), and sectoral (within each of six sectoral areas: superior, superotemporal, superonasal, inferior, inferonasal, and inferotemporal). The stage of AMD was graded on color fundus photographs in accordance with the Beckman Initiative for Macular Research classification system. Of 1339 subjects enrolled in the Amish eye study, a total of 1294 eyes of twelve hundred and ninety-four subjects had all required imaging studies of sufficient quality and were included in the final analysis, and of these 798 (62%) were female. Following age adjustment, the average GCC thickness was significantly (p<0.001) thinner in AMD subjects (73.71 ± SD; 13.77 µm) compared to normals (77.97 ± 10.42 µm). Independent t test showed that, early (75.03 ± 12.45 µm), and late AMD (61.64 ± 21.18 µm) groups (among which GA eyes had the lowest thickness of 58.10 ± 20.27 microns) had a statistically significant lower GCC thickness compared to eyes without AMD. There was no significant difference in average GCC thickness between early AMD and intermediate AMD (76.36 ± 9.25 µm) eyes. The GCC thickness in AMD eyes is reduced compared to normal eyes, but the relationship is complex with the greatest reduction in late AMD eyes (particularly GA eyes) but no difference between early and intermediate AMD eyes.

Pro re nata anti-VEGF treatment in pachychoroid neovasculopathy compared with age-related macular degeneration based on optical coherence tomography.

To compare anti-vascular endothelial growth factor (anti-VEGF) treatment in pachychoroid neovasculopathy (PNV) and age related macular degeneration (AMD). Cases having pro re nata (PRN) anti-VEGF treatment for choroidal neovascularization were reviewed and grouped as PNV and AMD. Groups were compared according to central foveal thickness (CFT), best corrected visual acuity (BCVA), and total injection over 12months. The correlation of beginning choroidal thickness, CFT, and BCVA with final BCVA was analyzed. Forty-seven PNV and 65 AMD cases were reviewed. Both the PNV group (p = 0.0001) and the AMD group (p = 0.003) had a significant improvement in BCVA and a significant decrease in CFT (p = 0.0001). However, BCVA was better at the 3-, 6-, and 12-month follow-up in PNV (p = 0.003, 0.002, 0.02). No significant CFT difference was observed between groups. The total number of injections was 5.7 ± 1.7 for PNV and 5.2 ± 1.5 for AMD (p = 0.09). Beginning BCVA was positively correlated with final BCVA in both groups. The PRN treatment regimen was effective for PNV and AMD in terms of visual and anatomical outcomes. Visual response was better in PNV with PRN treatment with the same number of injections.

Repeatability of Rod-Mediated Dark Adaptation Testing in Normal Aging and Early and Intermediate Age-Related Macular Degeneration.

The vulnerability of rod photoreceptors in aging and early and intermediate age-related macular degeneration (AMD) has been well documented. Rod-mediated dark adaptation (RMDA) is a measure of the recovery of light sensitivity in rod photoreceptors following a bright light. Delays in RMDA during early and intermediate AMD have been widely reported. For RMDA's promise as an outcome for trials targeted at early and intermediate AMD to be realized, excellent test-retest reliability, its repeatability, must be established. Test-retest performance in a commonly used RMDA test based on the rod intercept time metric (RIT) was evaluated in participants with early and intermediate AMD and with normal retinal aging with testing approximately 2 weeks apart. The test target was placed at 5° eccentricity superior to the foveal center, an area with maximal rod loss in aging and AMD. Disease severity was identified by a trained and masked grader of fundus photographs using both the AREDS 9-step and Beckman classification systems. Bland-Altman plots and intra-class correlation coefficients (ICC) evaluated repeatability. The analysis sample consisted of 37 older adults (mean age 76 years, standard deviation 5), with approximately one-third of the sample in each of three groups - normal aging, early AMD, and intermediate AMD. For the total sample, the ICC was 0.98. For individual AMD groups for both AREDS 9-step and Beckman classifications, the ICCs were also very high ranging from 0.82 to 0.99. We demonstrated that RMDA testing using the RIT metric has excellent repeatability when target location is at 5° in studying older adults from normal aging to intermediate AMD, suggesting the reliable use of this functional measure in trials.

Metabolic activity of visceral adipose tissue is associated with age-related macular degeneration: a pilot 18F-FDG PET/CT study.

Obesity is known to increase the risk and severity of age-related macular degeneration (AMD). Increased inflamed metabolic activity of visceral adipose tissue (VAT) is considered as a crucial underlying mechanism for the harmful effects of obesity. In this study, we aimed to investigate the inflamed metabolic activity of VAT with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and their association with AMD. A total of 57 elderly participants (aged ≥ 50 years) who underwent 18F-FDG PET/CT for health screening and subsequent fundoscopic exam for complaint of recently impaired vision were enrolled. The metabolic activity of VAT was measured from the maximum standardized uptake value (SUVmax) of VAT. The early AMD participant was defined as the participant with either eye satisfying AMD and without any sign of advanced AMD (neovascular AMD or geographic atrophy). The late AMD participant was defined as the participant with either eye satisfying advanced AMD. VAT SUVmax was highest in participants with late AMD, intermediate in early AMD, and lowest in non-AMD participants. The levels of systemic inflammation surrogate markers were also highest in late AMD group. Furthermore, VAT SUVmax was positively correlated with systemic inflammation surrogate markers and independently associated with the late AMD. The metabolic activity of VAT evaluated by 18F-FDG PET/CT was associated with the severity of AMD and synchronized with the level of systemic inflammation. Thus, VAT SUVmax could be potentially employed as a surrogate marker of obesity-driven VAT inflammation associated with AMD.

Association of TAS2R16 gene (rs860170, rs978739, rs1357949) polymorphisms and TAS2R16 serum levels in patients with age-related macular degeneration

ABSTRACT Background The aim of this study is to determine the association of TAS2R16 (rs860170, rs978739, rs1357949) gene polymorphisms and TAS2R16 serum levels in patients with the occurrence of age-related macular degeneration (AMD). Methods Subjects with early AMD, subjects with exudative AMD, and healthy controls participated in the study. DNA was isolated by salting out leukocytes from peripheral venous blood. Single nucleotide polymorphisms (SNPs) were analysed by RT-PCR. TAS2R16 levels were determined by enzyme-linked immunosorbent assay (ELISA) using the Abbexa Human Taste Receptor Type 2 Member 16 (TAS2R16) ELISA kit. Statistical data analysis was performed using “IBM SPSS Statistics 27.0” and SNPstats statistical data analysis programmes. Results The TAS2R16 rs860170 TT genotype is statistically significantly less frequent in the exudative AMD group than in the control group, whereas the TAS2R16 rs860170 C allele gene is statistically significantly more frequent in the exudative AMD group. Each C allele of TAS2R16 rs860170 is associated with a 2.8-fold increased probability of occurrence of exudative AMD. The C allele of TAS2R16 rs860170 is statistically significantly more frequent in men and women with exudative AMD than in the control group. The C allele of TAS2R16 rs860170 is associated with a 2.8-fold increased odds of occurrence of exudative AMD in women and a 2.9-fold increased odds of occurrence of exudative AMD in men. In TAS2R16 (rs860170, rs978739, and rs1357949), the T-T-A haplotype is associated with a 2.6-fold decreased likelihood of developing early AMD and the T-T-A haplotype is associated with a 3.2-fold decreased likelihood of developing early AMD in women. For TAS2R16 (rs860170, rs978739, and rs1357949), carriers of the T-T-G and T-T-A haplotypes are associated with a 2.2- and 3.2-fold decreased probability of exudative AMD, respectively. Individuals with the C-C-A haplotype are 9.2-fold more likely to develop exudative AMD. Specifically, the C-C-A haplotype is associated with a 9.3-fold increased likelihood of exudative AMD in men. In contrast, women with the T-T-A haplotype are 5.6-fold less likely to develop exudative AMD. Conclusion TAS2R16 plays an important role in the development of AMD.

Patient-Centered Economic Burden of Exudative Age-Related Macular Degeneration: Retrospective Cohort Study.

Exudative age-related macular degeneration (AMD), one of the leading causes of blindness, requires expensive drugs such as anti-vascular endothelial growth factor (VEGF) agents. The long-term regular use of effective but expensive drugs causes an economic burden for patients with exudative AMD. However, there are no studies on the long-term patient-centered economic burden of exudative AMD after reimbursement of anti-VEGFs. This study aimed to evaluate the patient-centered economic burden of exudative AMD for 2 years, including nonreimbursement and out-of-pocket costs, compared with nonexudative AMD using the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). This retrospective cohort study was conducted using the OMOP CDM, which included 2,006,478 patients who visited Seoul National University Bundang Hospital from June 2003 to July 2019. We defined the exudative AMD group as patients aged >50 years with a diagnosis of exudative AMD and a prescription for anti-VEGFs or verteporfin. The control group was defined as patients aged >50 years without a diagnosis of exudative AMD or a prescription for anti-VEGFs or verteporfin. To adjust for selection bias, controls were matched by propensity scores using regularized logistic regression with a Laplace prior. We measured any medical cost occurring in the hospital as the economic burden of exudative AMD during a 2-year follow-up period using 4 categories: total medical cost, reimbursement cost, nonreimbursement cost, and out-of-pocket cost. To estimate the average cost by adjusting the confounding variable and overcoming the positive skewness of costs, we used an exponential conditional model with a generalized linear model. We identified 931 patients with exudative AMD and matched 783 (84.1%) with 2918 patients with nonexudative AMD. In the exponential conditional model, the total medical, reimbursement, nonreimbursement, and out-of-pocket incremental costs were estimated at US $3426, US $3130, US $366, and US $561, respectively, in the first year and US $1829, US $1461, US $373, and US $507, respectively, in the second year. All incremental costs in the exudative AMD group were 1.89 to 4.25 and 3.50 to 5.09 times higher in the first and second year, respectively, than those in the control group (P<.001 in all cases). Exudative AMD had a significantly greater economic impact (P<.001) for 2 years on reimbursement, nonreimbursement, and out-of-pocket costs than nonexudative AMD after adjusting for baseline demographic and clinical characteristics using the OMOP CDM. Although economic policies could relieve the economic burden of patients with exudative AMD over time, the out-of-pocket cost of exudative AMD was still higher than that of nonexudative AMD for 2 years. Our findings support the need for expanding reimbursement strategies for patients with exudative AMD given the significant economic burden faced by patients with incurable and fatal diseases both in South Korea and worldwide.

Comparative analysis of alignment algorithms for macular optical coherence tomography imaging

BackgroundOptical coherence tomography (OCT) is the most important and commonly utilized imaging modality in ophthalmology and is especially crucial for the diagnosis and management of macular diseases. Each OCT volume is typically only available as a series of cross-sectional images (B-scans) that are accessible through proprietary software programs which accompany the OCT machines. To maximize the potential of OCT imaging for machine learning purposes, each OCT image should be analyzed en bloc as a 3D volume, which requires aligning all the cross-sectional images within a particular volume.MethodsA dataset of OCT B-scans obtained from 48 age-related macular degeneration (AMD) patients and 50 normal controls was used to evaluate five registration algorithms. After alignment of B-scans from each patient, an en face surface map was created to measure the registration quality, based on an automatically generated Laplace difference of the surface map–the smoother the surface map, the smaller the average Laplace difference. To demonstrate the usefulness of B-scan alignment, we trained a 3D convolutional neural network (CNN) to detect age-related macular degeneration (AMD) on OCT images and compared the performance of the model with and without B-scan alignment.ResultsThe mean Laplace difference of the surface map before registration was 27 ± 4.2 pixels for the AMD group and 26.6 ± 4 pixels for the control group. After alignment, the smoothness of the surface map was improved, with a mean Laplace difference of 5.5 ± 2.7 pixels for Advanced Normalization Tools Symmetric image Normalization (ANTs-SyN) registration algorithm in the AMD group and a mean Laplace difference of 4.3 ± 1.4.2 pixels for ANTs in the control group. Our 3D CNN achieved superior performance in detecting AMD, when aligned OCT B-scans were used (AUC 0.95 aligned vs. 0.89 unaligned).ConclusionsWe introduced a novel metric to quantify OCT B-scan alignment and compared the effectiveness of five alignment algorithms. We confirmed that alignment could be improved in a statistically significant manner with readily available alignment algorithms that are available to the public, and the ANTs algorithm provided the most robust performance overall. We further demonstrated that alignment of OCT B-scans will likely be useful for training 3D CNN models.

Vision-Related Quality of Life among Patients with Different Types of Age-Related Macular Degeneration.

This study aimed to assess the vision-related quality of life (VRQol) of patients with age-related macular degeneration (AMD) and to evaluate VRQol according to different types of AMD. In this small-scale, single-center, prospective investigation, patients with AMD and subjects without any signs of macular disease were asked to complete the NEI-VFQ-39. A total of 159 subjects were included and grouped according to the type of AMD as follows: 40 patients with dry AMD in both eyes (DD), 40 patients with exudative AMD in one eye (DE), 41 patients with exudative AMD in both eyes (EE), and 38 subjects without any signs of macular disease, as a control group (CG). The average age of the participants was 76 ± 7 years, and 44% were male. Most participants were retired (22.4%), and 75% of patients were initially diagnosed by their ophthalmologist. All the AMD groups had significantly worse overall VRQol than the CG. For general vision, near vision, mental health, and role difficulties, all the AMD groups had significantly lower scores than the CG. For distance vision, color vision, peripheral vision, driving difficulties, dependency, and social functioning, only patients in the EE and DE groups had significantly worse scores than the CG. The type of retinal fluid in patients with exudative AMD had no effect on overall VRQol; however, we found that the presence of pigment epithelial detachment could be associated with more role difficulties, such as completing work or working long hours. All types of AMD had a negative effect on vision-related quality of life. This effect was significantly more pronounced in patients with exudative AMD in at least one eye. However, the type of retinal fluid in patients with exudative AMD had no influence on their overall vision-related quality of life.

Impact of Central Vision Loss on Eye Movements and Time-to-Contact Judgments

Age-related macular degeneration (AMD) leads to loss of central vision and typically occurs in older adults. Loss of central vision has been associated with degraded mobility, including difficulties with streetcrossing decisions, which implies that there also may be degraded timeto-contact (TTC) judgments. Further, individuals with AMD have shorter saccades compared to individuals with normal vision leading to difficulty with tracking objects. This study investigated the impact of eye movements on TTC judgments in an AMD group using a predicted motion task in a virtual reality system. Results indicated that longer saccades were associated with more accurate TTC judgments and showed that the AMD group had shorter saccades, and less accurate TTC judgments. As such, difficulties with judgments of collisions in individuals with AMD may result from inefficient eye movements.

Indocyanine green angiography of type 1 macular neovascularization in age-related macular degeneration and central serous chorioretinopathy reveals different disease mechanisms.

To assess the rate of late phase hyperfluorescent plaque (LPHP) in type 1 macular neovascularization (MNV) in CSCR (central serous chorioretinopathy) and AMD (age-related macular degeneration) and to evaluate its prognostic value. Retrospective study including type 1 MNV in AMD and CSCR, from 2012 to 2020. Eyes with a late ICG-A image (>20mins) and clear visualization of MNV on OCTA were included. Quantitative and qualitative parameters on OCT and best corrected visual acuity were recorded at baseline, and after 3 monthly anti-VEGF injections. Eighty-three eyes were included, 35 with CSCR and 48 with AMD. Patients in the CSCR group were significantly younger than in the AMD group (61.3 ± 10.4 vs. 80.2 ± 6.8 years respectively, p<0.001), predominantly male (68.6% CSCR vs 35.4% AMD; p=0.003) and with a thicker choroid (379 ± 93.3 μm vs 204.2 ± 93.2 μm; p<0.001). Type 1 MNV in CSCR showed fewer LPHP compared to AMD (31.4% vs 77.1%; p<0.001). Baseline visual acuity was lower in patients with LPHP (0.37± 0.22 vs 0.27 ±0.28 LogMAR, p=0.03). On multivariate analysis, AMD was associated with the presence of LPHP (p<0.001). No significant difference in the response to anti-VEGF was observed. Leakage of macromolecules from MNV and accumulation in the RPE and/or in the stroma imaged by the LPHP is less common in eyes with type 1 MNV in CSCR than in AMD. Late phase ICG-A imaging offers an insight into the metabolism of the dye and the environment surrounding the neovascular membrane.

Effect of repeated intravitreal anti-vascular endothelial growth factor drugs on corneal nerves.

To investigate the potential effect of repeated intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs on corneal nerves. A total of 64 patients were treated with intravitreal injection of anti-VEGF drugs. There were 19 cases of neovascular age-related macular degeneration (AMD), 20 cases of diabetic macular edema (DME) and 25 cases of retinal vein occlusion (RVO). Twenty-nine cases were treated with aflibercept (2 mg/0.05 mL) whereas 35 cases were managed with ranibizumab (0.5 mg/0.05 mL). A corneal confocal microscope was used to collect images of corneal subbasal nerve plexus, and Image J was used for image analysis. The changes in corneal nerve were compared between 1 month after each injection and before injection. There were no significant differences in the density and length of corneal nerve at specific time after the surgery in comparison with baseline in patients who were given 3 intravitreal injections. There was no significant correlation between the numbers of injections and the changes of the corneal nerves. After 3rd injection, the nerve length of the DME group was markedly lower than that of AMD and RVO groups, the difference was statistically significant (P < .05). The nerve density of the DME group was not significantly different from that of AMD and RVO groups, whereas the nerve length and nerve density of the AMD and RVO groups were not statistically significant between each other also. The corneal nerve length after the 2nd and 3rd injections of Aflibercept were lower than that before surgery, the difference was statistically significant. There were no significant differences in nerve density and nerve length at each time point after Ranibizumab injection. The length and density of the corneal nerve after multiple injections in contralateral eye displayed no significant changes compared with the baseline. Repeated intravitreal anti-VEGF drug can reduce the length of corneal nerves. For patients who need repeated intravitreal injections of anti-VEGF drugs, especially in DM, attention should be paid on the changes affecting the corneal nerves. It is also needed to strengthen the local anti-inflammatory therapy to avoid infection and to use artificial tears to protect the microenvironment of the ocular surface after the surgery.

Analysis of Retinol Binding Protein 4 and ABCA4 Gene Variation in Non-Neovascular Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) may be associated with ABCA4 variants and is characterized by the accumulation of visual cycle-byproduct lipofuscin. Reducing retinol-binding protein 4 (RBP4), a retinol transporter protein, may reduce lipofuscin production. This study aims to assess the associations between plasma RBP4, the ABCA4 variation, and AMD severity. Sixty-seven participants were grouped into healthy/mild AMD (n = 32) and severe AMD (n = 35) groups. The latter group was older than the former group and had higher levels of RBP4 (36.8 ± 8.3 vs. 30.4 ± 7.0 μg/mL, p = 0.0012). The ten participants with six ABCA4 linked-variants had higher RBP4 than those without (37.8 ± 7.7 vs. 32.4 ± 7.9 μg/mL; p = 0.026), and eight of them had severe AMD. Univariate analyses showed that severe AMD was related to older age (OR, 1.26; 95% CI, 1.13-1.40; p < 0.0001) and to higher RBP4 levels (OR, 1.12; 95% CI, 1.04-1.20; p = 0.003), whereas the linked ABCA4 variants had no associations. After adjustment, however, only age remained significantly associated with severe AMD. This pilot study shows a trend of higher plasma RBP4 levels in severe AMD or the ABCA4-linked variants, and further age-matched studies are warranted.

Analysis of Aqueous Humor Cytokines in Exudative Age-related Macular Degeneration and Diabetic Macular Edema

Purpose: To investigate the cytokine concentrations of aqueous humor in patients with exudative age-related macular degeneration (AMD) and diabetic macular edema (DME).Methods: Fifty-seven subjects were included in the exudative AMD, DME and control groups, each group has 19 patients. Aqueous levels of cytokines epidermal growth factor (EGF), vascular endothelial growth factor-C (VEGF-C), monocyte chemoattractant protein-1 (MCP-1), hepatocyte growth factor (HGF), interleukin (IL)-3, IL-8, IL-6, IL-12p40, intercellular adhesion molecule 1 (ICAM-1) were investigated in each groups. Kruskal-Wallis test and Mann-Whitney U test were performed to compare cytokine concentrations.Results: Aqueous levels of EGF, VEGF-C, MCP-1, HGF, IL-3, IL-8 were significantly higher in exudative AMD group than control group (&lt;i&gt;p&lt;/i&gt; = &lt; 0.0001, &lt; 0.0001, 0.004, 0.015, &lt; 0.0001, 0.014) and EGF, VEGF-C, IL-3, IL-8 were significantly higher in DME group than control group (&lt;i&gt;p&lt;/i&gt; = &lt; 0.0001, &lt; 0.0001, &lt; 0.0001, 0.005). In the comparison between the exudative AMD and DME groups, EGF was significantly higher in the exudative AMD group (&lt;i&gt;p&lt;/i&gt; = 0.001).Conclusions: Various cytokines were increased in patients with exudative AMD and DME. In particular, EGF showed a higher level in exudative AMD than in DME.

A Workflow to Quantitatively Determine Age-Related Macular Degeneration Lesion-Specific Variations in Fundus Autofluorescence.

Fundus autofluorescence (FAF) imaging allows the noninvasive mapping of intrinsic fluorophores of the ocular fundus, particularly the retinal pigment epithelium (RPE), now quantifiable with the advent of confocal scanning laser ophthalmoscopy-based quantitative autofluorescence (QAF). QAF has been shown to be generally decreased at the posterior pole in age-related macular degeneration (AMD). The relationship between QAF and various AMD lesions (drusen, subretinal drusenoid deposits) is still unclear. This paper describes a workflow to determine lesion-specific QAF in AMD. A multimodal in vivo imaging approach is used, including but not limited to spectral domain optical coherence tomography (SD-OCT) macular volume scanning and QAF. Using customized FIJI plug-ins, the corresponding QAF image is aligned with the near-infrared image from the SD-OCT scan (characteristic landmarks; i.e., vessel bifurcations). The foveola and the edge of the optic nerve head are marked in the OCT images (and transferred to the registered QAF image) for accurate positioning of the analysis grids. AMD-specific lesions can then be marked on individual OCT BScans or the QAF image itself. Normative QAF maps are created to account for the varying mean and standard deviation of QAF values throughout the fundus (QAF images from a representative AMD group were averaged to build normative standard retinal QAF AMD maps). The plug-ins record the X and Y coordinates, z-score (a numerical measurement that describes the QAF value in relation to the mean of AF maps in terms of standard deviation from the mean), mean intensity value, standard deviation, and number of pixels marked. The tools also determine z-scores from the border zone of marked lesions.This workflow and the analysis tools will improve the understanding of the pathophysiology and clinical AF image interpretation in AMD.

Does the Presence of the Cilioretinal Artery Affect the Incidence, Clinical Picture and Progression of Age-Related Macular Degeneration?

The aims of this study were to analyze the relationship between the presence of the cilioretinal artery (CRA) and the incidence, severity and progression of age-related macular degeneration (AMD) and to estimate the influence of the CRA on choroidal and retinal parameters. A total of 287 patients with AMD and 110 healthy controls were enrolled in the study. CRA occurrence was determined using color fundus images. AMD progression was assessed after 3 years. There was no difference in the incidence of CRA between the AMD and control groups (23.34% vs. 24.55%; p = 0.8). Lower-stage AMD was more frequently observed in eyes with the CRA than in eyes without the artery (p = 0.016). The CRA did not influence disease progression (p = 0.79). The CRA did not influence retinal and choroidal thickness and volume parameters or the retinal vessel caliber and functionality in either the AMD or control groups. There was no relationship between CRA presence and CFH Y402H and ARMS2 A69S risk variants. The results did not show a protective effect of the CRA on the incidence and progression of AMD. The CRA may affect the severity of AMD; however, the mechanism of this phenomenon is unclear.

Evaluation of systemic immune-inflammatory index in patients with wet age-related macular degeneration

ABSTRACT Clinical relevance The systemic immune-inflammatory index is a relatively new parameter and has been shown to increase in inflammatory diseases. Background The primary aim of this study was to investigate the systemic immune-inflammatory index in patients with wet-type age-related macular degeneration. The secondary aim was to determine the relationship between best-corrected visual acuity, central macular thickness, subfoveal choroidal thickness, systemic immune-inflammatory index, platelet-to-lymphocyte ratio, and neutrophil-to-lymphocyte ratio. Methods This study retrospectively analysed patients with wet-type age-related macular degeneration between 2018 and 2022. Demographic data and peripheral complete blood count were obtained from the electronic medical record system. The most recent best-corrected visual acuity, central macular thickness, and subfoveal choroidal thickness values (within one month) for complete blood count were obtained from case sheets and the optical coherence tomography digital image database. The systemic immune-inflammatory index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio were calculated. Age- and sex-matched controls were also generated. Results Thirty-three patients (23 males, 10 females) with wet-type age-related macular degeneration and 43 controls (24 males, 19 females) were included. The groups were similar in terms of age and sex (78.0 ± 6.3 vs. 75.6 ± 6.6 years, p = 0.59; p = 0.38 for sex). The systemic immune-inflammatory index was higher in the wet-type age-related macular degeneration group (460.5 vs. 440.4); however, this difference was not statistically significant. When the correlations between the systemic immune-inflammatory index, platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, best-corrected visual acuity (logMAR), central macular thickness, and subfoveal choroidal thickness were examined, there was only a moderate positive correlation between best-corrected visual acuity and platelet-to-lymphocyte ratio (r = 0.46, p = 0.007). Conclusion There were no differences in the systemic immune-inflammatory index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio between the wet-type age-related macular degeneration and control groups. There was a positive correlation between the platelet-to-lymphocyte ratio and best-corrected visual acuity (logMAR). The systemic immune-inflammatory index was higher in patients with wet-type age-related macular degeneration than in the control group; however, this difference was not statistically significant.