-
1.
Effects of Zinc Acetate Hydrate Treatment on Serum Oxidative Stress Markers in Patients with Macular Drusen.
Mano, F, Sakata, S, Chang, KC, Mano, T
Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics. 2021;(9):518-524
Abstract
Purpose: To measure the serum levels of the oxidative stress markers superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GPx) and compare them before and after zinc supplementation in patients with early age-related macular degeneration (AMD). Methods: We measured serum zinc levels in 65 patients with early AMD. Of these, 29 patients with macular drusen and a serum zinc level <80 μg/dL received oral zinc acetate dihydrate (50 mg/day). Serum trace metal levels (zinc and copper) and oxidative stress marker levels (SOD, MDA, and GPx) were measured at baseline and 12 weeks after the treatment. The macular drusen areas and best-corrected visual acuity were evaluated in 24 participants who attended the 3-month follow-up. Results: MDA level was significantly decreased from baseline to 12 weeks after zinc administration (170.5 ± 100.9 vs. 148.3 ± 57.9 pmol/mL, P = 0.03), while SOD was significantly increased from baseline to 12 weeks after zinc intake (4.2 ± 0.9 vs. 4.6 ± 0.9 U/mL, P = 0.03). The serum zinc level was significantly correlated with the MDA level (P = 0.03, ρ = -0.26). The area of soft drusen was significantly decreased after zinc treatment (1,936,654.9 ± 1,348,267.6 vs. 966,883.9 ± 719,938.1 μmm2, P = 0.04). Conclusions: The levels of oxidative stress markers MDA and SOD decreased and increased, respectively, after oral zinc administration to 24 patients with AMD. The therapeutic effect of zinc treatment on drusen area might differ depending on the drusen phenotype in early AMD.
-
2.
Diagnostic Accuracy of Technology-based Eye Care Services: The Technology-based Eye Care Services Compare Trial Part I.
Maa, AY, Medert, CM, Lu, X, Janjua, R, Howell, AV, Hunt, KJ, McCord, S, Giangiacomo, A, Lynch, MG
Ophthalmology. 2020;(1):38-44
Abstract
PURPOSE Ophthalmologic telemedicine has the ability to provide eye care for patients remotely, and many countries have used screening tele-ophthalmology programs for several years. One such initiative at the Veterans Affairs (VA) Healthcare System is Technology-based Eye Care Services (TECS). The TECS services are located in primary care clinics and provide basic screening eye care, including vision, refraction, and retinal photography. Eye care providers ("readers") review the clinical data and recommend appropriate follow-up. One of the most common referrals from TECS has been for glaucoma, and this study was powered for glaucoma/glaucoma suspect detection. The current study was undertaken to identify aspects of the protocol that could be refined to enhance accuracy. DESIGN Prospective comparison between the standard TECS protocol versus a face-to-face (FTF) examination on 256 patients, all of whom had no known history of significant ocular disease. PARTICIPANTS Patients with no known ocular disease who were scheduled for an in-person eye appointment at the Atlanta VA. Patients underwent screening through the TECS protocol and received an FTF examination on the same day (gold standard). The TECS readers were masked to the results of the FTF examination. MAIN OUTCOME MEASURES Percent agreement, kappa, sensitivity, and specificity were calculated for the TECS readers' interpretations versus the FTF examination. RESULTS The TECS readers showed substantial agreement for cataract (κ ≥ 0.71) and diabetic retinopathy (κ ≥ 0.61) and moderate to substantial agreement for glaucoma/glaucoma suspect (κ ≥ 0.52) compared with an FTF examination. Age-related macular degeneration (AMD) showed moderate agreement (κ ≥ 0.34). Percent agreement with the TECS protocol was high (84.3%-98.4%) for each of the disease categories. Overall sensitivity and specificity were ≥75% and ≥55%, respectively, for any diagnosis resulting in referral. Inter-reader and intra-reader agreement was substantial for most diagnoses (κ > 0.61) with percent agreements ranging from 66% to 99%. CONCLUSIONS Our results indicate that the standard TECS protocol is accurate when compared with an FTF examination for the detection of common eye diseases. The inclusion of additional testing such as OCT could further enhance diagnostic capability.
-
3.
Efficacy and Safety of Intravitreal Aflibercept Treat-and-Extend Regimens in Exudative Age-Related Macular Degeneration: 52- and 96-Week Findings from ALTAIR : A Randomized Controlled Trial.
Ohji, M, Takahashi, K, Okada, AA, Kobayashi, M, Matsuda, Y, Terano, Y, ,
Advances in therapy. 2020;(3):1173-1187
-
-
Free full text
-
Abstract
PURPOSE To evaluate efficacy and safety of intravitreal injections of aflibercept (IVT-AFL) treat-and-extend (T&E) dosing regimens in treatment-naïve patients with exudative age-related macular degeneration (AMD). METHODS Adults aged at least 50 years old with exudative AMD and best-corrected visual acuity (BCVA) of 73-25 Early Treatment Diabetic Retinopathy Study (ETDRS) letters were included. Patients received three monthly doses of IVT-AFL 2 mg. At week 16, patients were randomized 1:1 to IVT-AFL T&E with either 2- or 4-week adjustments. The primary endpoint was mean change in BCVA from baseline to week 52. Outcomes were assessed at weeks 52 and 96. RESULTS Baseline characteristics were comparable between the groups (n = 123 each). Over 52 weeks, mean number of injections was 7.2 and 6.9 and mean last injection interval was 10.7 and 11.8 weeks, for the 2- and 4-week groups, respectively. From baseline, mean change in BCVA was + 9.0 and + 8.4 letters (week 52) and + 7.6 and + 6.1 letters (week 96); mean change in central retinal thickness was - 134.4 µm and - 126.1 µm (week 52) and - 130.5 µm and - 125.3 µm (week 96). Last injection interval before week 52 was at least 12 weeks in 42.3% and 49.6% of patients and 56.9% and 60.2% before week 96. Over 96 weeks, mean number of injections was 10.4 (both groups). The safety profile of IVT-AFL was consistent with previous reports. CONCLUSIONS IVT-AFL administered using two different T&E regimens for treatment-naïve exudative AMD improved functional and anatomic outcomes at week 52 and outcomes were maintained to week 96. Outcomes were similar between the 2- and 4-week groups. TRIAL REGISTRATION ClinicalTrials.gov identifier, NCT02305238.
-
4.
The Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration: Results from the Randomized Phase 2 Ladder Clinical Trial.
Campochiaro, PA, Marcus, DM, Awh, CC, Regillo, C, Adamis, AP, Bantseev, V, Chiang, Y, Ehrlich, JS, Erickson, S, Hanley, WD, et al
Ophthalmology. 2019;(8):1141-1154
Abstract
PURPOSE To evaluate the safety and efficacy of the Port Delivery System with ranibizumab (PDS) for neovascular age-related macular degeneration (nAMD) treatment. DESIGN Phase 2, multicenter, randomized, active treatment-controlled clinical trial. PARTICIPANTS Patients diagnosed with nAMD within 9 months who had received 2 or more prior anti-vascular endothelial growth factor intravitreal injections and were responsive to treatment. METHODS Patients were randomized 3:3:3:2 to receive the PDS filled with ranibizumab 10 mg/ml, 40 mg/ml, 100 mg/ml, or monthly intravitreal ranibizumab 0.5-mg injections. MAIN OUTCOME MEASURES Time to first implant refill assessed when the last enrolled patient completed the month 9 visit (primary efficacy end point), improvement in best-corrected visual acuity (BCVA) and central foveal thickness (CFT), and safety. RESULTS The primary analysis population was 220 patients, with 58, 62, 59, and 41 patients in the PDS 10-mg/ml, PDS 40-mg/ml, PDS 100-mg/ml, and monthly intravitreal ranibizumab 0.5-mg arms, respectively. Median time to first implant refill was 8.7, 13.0, and 15.0 months in the PDS 10-mg/ml, PDS 40-mg/ml, and PDS 100-mg/ml arms, respectively. At month 9, the adjusted mean BCVA change from baseline was ‒3.2 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, ‒0.5 ETDRS letters, +5.0 ETDRS letters, and +3.9 ETDRS letters in the PDS 10-mg/ml, PDS 40-mg/ml, PDS 100-mg/ml, and monthly intravitreal ranibizumab 0.5-mg arms, respectively. At month 9, the adjusted mean CFT change from baseline was similar in the PDS 100-mg/ml and monthly intravitreal ranibizumab 0.5-mg arms. The optimized PDS implant insertion and refill procedures were generally well tolerated. After surgical procedure optimization, postoperative vitreous hemorrhage rate was 4.5% (7/157; 1 event classified as serious). There was no evidence of implant clogging. CONCLUSIONS In the phase 2 Ladder trial, the PDS was generally well tolerated and demonstrated a dose response across multiple end points in patients with nAMD. The PDS 100-mg/ml arm showed visual and anatomic outcomes comparable with monthly intravitreal ranibizumab 0.5-mg injections but with a reduced total number of ranibizumab treatments. The PDS has the potential to reduce treatment burden in nAMD while maintaining vision.
-
5.
Improvement in Vision Parameters for Participants Treated With Alternative Therapies in a 3-day Program.
Kondrot, EC
Alternative therapies in health and medicine. 2015;(6):22-35
Abstract
CONTEXT Eye conditions that are considered progressive and degenerative and for which the causation is generally poorly understood or not understood within conventional medicine can respond to natural therapeutic interventions that result in arrest and/or improvement of morbidity, with enhanced functional results. Because many of the treated conditions are age related, a delay of disease progression for 5 or even 10 y can mean an additional decade of independence for seniors. The 11 included ocular conditions are ordinarily considered incurable by any method except surgery and, even with surgery, the outcomes can be variable and/or transient. OBJECTIVE The research intended to demonstrate the effectiveness of alternative modalities-intravenous (IV) nutrition, oxidative therapy, microcurrent stimulation, and syntonic light therapy-in improving vision in chronic eye conditions, even when administered for a short period. DESIGN The study was a retrospective, open-label, single-group design. All participants in the 3-d conference during the period covered were selected. SETTING The setting was ophthalmologist Edward Kondrot's Healing the Eye and Wellness Center near Tampa, FL, USA. PARTICIPANTS The participants in this study were all patients attending 1 of 11 CAM treatment events at the author's center within 2 y. Each session lasted 3 d and the number of participants in each session ranged from 5-15 (mean = 13). The cohort numbered 152 patients who were diagnosed with ≥1 of 11 types of eye disease. Seventy-eight percent of the patients had either age-related macular degeneration (ARMD) or glaucoma, which, taken together, are the leading cause of blindness in persons >65 y. INTERVENTION Each of 4 alternative modalities was provided at least once to each participant: (1) IV nutrition, (2) oxidative therapy, (3) microcurrent stimulation, and (4) syntonic light therapy. On the first day, a detailed treatment plan for each participant was developed. Each day consisted of 2 therapeutic eye programs, a stress reduction program, and a detoxification program. Also included were daily lectures and instructions on the methods and use of the equipment. OUTCOME MEASURES To measure outcomes, changes from baseline were documented through comparison with postprogram results. Pre- and postprogram testing included the following measures: (1) Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart; (2) Lighthouse Letter Contrast Sensitivity test; (3) campimetry; (4) pursuits, saccade, and fixation tests; (5) pupillary examination; (6) external examination; (7) examination of the anterior segment; (8) intraocular-pressure test; and (9) dilated examination. Additional tests, if necessary, included (1) ocular coherence tomography, (2) infrared thermography, (3) 6-hour urine collection for heavy-metal toxicity, and (4) nocturnal oximetry. RESULTS All participants remained in the study for the duration of the program. Following the administration of the protocol, significant improvement in acuity, contrast, and visual field resulted in the majority of participants. None of the interventions was toxic or painful, and all likely contributed to an improved, overall health status for participants. CONCLUSIONS These treatment protocols should be considered part of a treatment program for all ocular disease processes. Eye health needs to be repositioned within an assessment of general health with the understanding that, with the exception of congenital disorders or accidents, vision decline represents a general diminishment in overall health and results directly from toxicity from both external sources such as air and water, and the internal accumulation of toxic metals; poor nutrition; and other life exposures and habits. Long-term follow-up studies are now in process.
-
6.
Changes in Macular Pigment Optical Density and Serum Lutein Concentration in Japanese Subjects Taking Two Different Lutein Supplements.
Obana, A, Tanito, M, Gohto, Y, Okazaki, S, Gellermann, W, Bernstein, PS
PloS one. 2015;(10):e0139257
Abstract
PURPOSE To investigate macular pigment optical density (MPOD) and serum concentration changes of lutein in Japanese subjects participating in a clinical trial in which two formulations of lutein and zeaxanthin supplements with different physiochemical properties are used. METHODS Thirty-six healthy volunteers were recruited into this prospective, randomized, parallel-group, double-masked comparative study at a single institute. Two products were used, FloraGLO® (Kemin Japan) and XanMax® (Katra Phytochem). The lutein particle size and zeaxanthin concentrations differed between the formulations. The subjects consumed one of the two supplements for a duration of up to 6 months. MPOD levels were measured by resonance Raman spectrometry at baseline and once a month until the end of the study. Serum lutein concentration was measured at baseline, month 3, and month 6. The subjects were also tested for contrast sensitivity, glare sensitivity, visual acuity, and in addition had a focal electroretinogram measured. RESULTS The mean serum lutein concentrations increased significantly after the first three months, but the mean MPOD levels in either supplement group did not show any statistically significant increase. A detailed analysis, however, revealed three response patterns in both groups for the increase of MPOD levels and serum lutein concentration, i.e. "retinal responders", who had an increase of both MPOD levels and serum lutein concentrations (n = 13), "retinal non-responders", who had only increased serum concentrations and no change in MPOD levels (n = 20), and "retinal and serum non-responders", who had neither MPOD level nor plasma concentration increases (n = 3). The subjects with low MPOD levels at baseline appeared to show increased MPOD levels at the 6 month time point upon lutein supplementation (r = -0.4090, p = 0.0133). Glare sensitivity improved in retinal responders in both supplement groups, while there were no remarkable changes in contrast sensitivity. CONCLUSIONS No statistically significant differences could be detected for MPOD levels and serum lutein concentrations between the two investigated lutein supplement formulations. Responses to lutein supplementation regarding MPOD levels and serum lutein concentrations varied between subjects. Subjects with lower MPOD levels at baseline responded well to lutein supplementation. However, since the number of subjects was low, a further study with more subjects is needed to prove that subjects with low MPOD levels will benefit from lutein supplementation. TRIAL REGISTRATION UMIN-CTR UMIN000004593.
-
7.
Intravitreal combination of dexamethasone sodium phosphate and bevacizumab in the treatment of exudative AMD.
Vakalis, N, Echiadis, G, Pervena, A, Deligiannis, I, Kavalarakis, E, Giannikakis, S, Papaefthymiou, I
Scientific reports. 2015;:8627
Abstract
The purpose of this study is to investigate the efficacy and safety of intravitreal dexamethasone sodium phosphate (DSP) combined with bevacizumab for the treatment of neovascular age-related macular degeneration (AMD). In this non comparative case study, 30 eyes of 27 patients with CNV due to AMD received intravitreal DSP (0.2 mg) and bevacizumab (1.25 mg) during a 6-month PRN (pro re nata) dosing regimen. Visual acuity, macular thickness and intraocular pressure (IOP) were monitored and recorded. After 6 months, mean retinal thickness decreased from 423.5 ± 75.3 to 228.2 ± 34.5 and mean visual acuity improved from 0.9 ± 0.39 logMAR to 0.53 ± 0.34 (p = 0.001) logMAR. During the trial period, 81 intravitreal injections were performed in 30 eyes, thus the mean number of injections per eye was 2.7 ± 1.1. 86.7% of the eyes required 3 or less injections while only 13.3% needed 4 or more injections. None of the patients, phakic or pseudophakic, manifested an elevation of IOP during the treatment, ranging between 12 and 22 mmHg. Combined DSP and bevacizumab offers encouraging results in the challenge of AMD treatment, providing immediate response of macular edema, reduced number of intravitreal injections and stabilization or improvement of visual acuity.
-
8.
Macular pigment density at the site of altered fundus autofluorescence.
Rothenbuehler, SP, Wolf-Schnurrbusch, UE, Wolf, S
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2011;(4):499-504
-
-
Free full text
-
Abstract
BACKGROUND The purpose of our study was to determine whether abnormalities of increased or decreased fundus autofluorescence (FAF) are associated with local changes in macular pigment (MP) optical density in patients with age-related maculopathy (ARM) and macular degeneration (ARMD). METHODS FAF imaging and MP measurement was performed through dilated pupils using a modified confocal scanning laser ophthalmoscope (HRA, Heidelberg Engineering, Germany) according to a standard protocol. Two-wavelength autofluorescence method was employed for determination of local macular pigment optical density (LMPOD). Image analysis and measurement of LMPOD at the area of altered FAF was performed using Heidelberg Eye Explorer Software. Mean values of LMPOD at the site of FAF abnormality were compared to an adjacent location with normal background FAF of the same image. RESULTS Sixty-three eyes of 63 patients (28 male, 35 female, mean age 75.8 ± 8.8 years) were included in this analysis. Group 1 comprised 31 cases with focal increased FAF. Mean LMPOD in the area of increased FAF was 0.073 ± 0.083 compared to 0.075 ± 0.074 in the adjacent area of normal FAF. Group 2 comprised 32 cases of focal decreased FAF. Mean LMPOD in the area of decreased FAF was -0.004 ± 0.088 compared 0.053 ± 0.075 in the adjacent area of normal FAF. The site of increased FAF showed no significant difference in LMPOD (p = 0.927) compared to adjacent areas of normal FAF, while areas of decreased FAF revealed significantly lower LMPOD (p = 0.001) compared to adjacent areas of normal FAF. CONCLUSIONS Focal increases of FAF due to ARM or ARMD did not lead to change in LMPOD. Presumably, retinal layers containing MP are unaffected by these processes. For lesions exhibiting focal decreased FAF, a reduction of LMPOD cannot be excluded. Further studies are needed to investigate MP in the course of disease.
-
9.
Treatment of neovascular age-related macular degeneration with a variable ranibizumab dosing regimen and one-time reduced-fluence photodynamic therapy: the TORPEDO trial at 2 years.
Spielberg, L, Leys, A
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2010;(7):943-56
Abstract
BACKGROUND The combination of verteporfin photodynamic therapy (PDT) and anti-angiogenics has been shown to be safe and efficacious in the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The purpose of this study is to demonstrate long-term prevention of vision loss and improvement in best-corrected visual acuity (BCVA) after treatment with one-time reduced-fluence-rate PDT followed by administration of ranibizumab on a variable dosing regimen over 24 months in patients with neovascular AMD. Secondary outcome measures included the change in central macular thickness (CMT), reinjection frequency, and safety. METHODS This prospective, nonrandomized, open-label, single-center study enrolled 27 consecutive patients (27 eyes) presenting at the Leuven University Eye Hospital with previously untreated, active neovascular AMD between September 2006 and January 2007. All patients were treated with one-time, reduced-fluence-rate verteporfin PDT, followed by intravitreal ranibizumab 0.5 mg on the same day. A second and third ranibizumab injection were given at weeks 4 and 8, respectively, after which patients were followed up monthly for 24 months. Additional treatment with ranibizumab was administered to eyes with active neovascularization as indicated clinically and on imaging studies. Retreatment was based on the following criteria: (1) presence of subretinal fluid (SRF), intraretinal edema or sub-retinal pigment epithelial fluid, as seen on OCT; (2) increase of CMT by >100 mm on OCT; (3) signs of active CNV leakage on fluorescein angiography; (4) new sub- or intraretinal hemorrhage; and (5) BCVA decreased of > or =5 letters on the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart. If any single criterion for reinjection was fulfilled, retreatment with ranibizumab was administered. RESULTS Twenty-five patients completed the 2-year study. Occult CNV was present in 64% and retinal angiomatous proliferative (RAP) lesions were present in 24% of the study eyes. The remaining three eyes had lesions classified as classic (one eye) or predominantly classic (two eyes) CNV. Month 24 data are available for 25 eyes (25 patients; age 55-86 years; mean 77; standard deviation (SD) = 7.2). Mean baseline VA was 58.6 letters (range: 35-70; SD = 8.4); 24-month VA was 66.2 letters (35-82; 12.7), not including one warfarin-treated patient who suffered vitreous hemorrhage. The mean visual acuity improved by 7.2 letters (p < 0.05) and the mean CMT decreased by 146 mum. VA improved >3 lines (15 letters) in 16%; improved 1-3 lines in 20%; remained within one line of baseline in 32%, decreased 1-3 lines in 16%, and decreased >3 lines in 16%. Losses of >3 lines were due to vitreous hemorrhage, geographic atrophy, fibrosis, and growth of an initially small CNV lesion. An average of 5.1 injections (range: 3-9) were administered during the first 12 months, and 7.1 injections (3-13) over 24 months. A total of 178 injections were performed; no systemic side-effects, uveitis, or choroidal collateral vascular damage were observed. Two patients were lost to follow-up. CONCLUSION Combined PDT and ranibizumab injection the same day was well tolerated in all patients. Eighty-four percent of patients had stable or improved vision at month 24.
-
10.
Quantitative analysis of central visual field defects in macular edema using three-dimensional computer-automated threshold Amsler grid testing.
Jivrajka, RV, Kim, JK, Fink, W, Sadun, AA, Sebag, J
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2009;(2):165-70
Abstract
PURPOSE To evaluate the central visual field (CVF) with specialized Amsler grid testing methods that include contrast sensitivity evaluation, in an attempt to detect abnormalities not identified with standard methods and to define new patterns of CVF deficits in two different diseases. METHODS 3D computer-automated threshold Amsler grid testing (3D-CTAG) was performed at five levels of contrast in one eye of 37 patients with diabetic macular edema (DME, n = 16) and exudative age-related macular degeneration (AMD, n = 21). RESULTS 3D-CTAG abnormalities were detected in six patients (16%) who had no abnormalities with conventional Amsler grid testing. DME patients had more foci of CVF deficits (3.56 +/- 2.92 defects/eye), than AMD patients (1.24 +/- 0.89 defects/eye; P < 0.0002). The shape of the 3D-CTAG abnormality in DME was an inverted cone, while the deficits in AMD were always cylindrical. All eyes showed significant increases in CVF deficit surface area at minimum contrast levels when compared to maximum contrast (295% greater with DME, P < 0.02 and 150% greater with AMD, P < 0.03). CONCLUSION 3D-CTAG detected CVF abnormalities not identified with conventional Amsler grid testing in 16% of subjects. Low-contrast conditions elicited a larger defect in both DME (3-fold) and AMD (1.5-fold). DME and AMD have unique 3D-CTAG profiles, enabling diagnostic discrimination. Measuring CVF defects with 3D-CTAG can quantitatively index disease severity and may be useful in longitudinal studies of the natural history of disease, as well as providing a quantitative outcome measure of the response to therapy.