Unilateral Neovascular Age-related Macular Degeneration Research Articles

Prevention Surpasses Treatment: 5-year Follow-Up, Cost-Utility, and Cost-Benefit of Zeaxanthin Therapy for Neovascular Age-Related Macular Degeneration.

Oral administration of zeaxanthin (Zx) 20mg daily in patients with unilateral neovascular age-related macular degeneration (nAMD) treated with triple therapy (photodynamic therapy/intravitreal bevacizumab/intravitreal dexamethasone) reduced fellow-eye 2-year nAMD incidence from 23 to 6% (p = 0.02) in a prior clinical trial. We questioned the long-term benefit and thus analyzed case-control 5-year patient data of trial participants and additional participants with 5-year follow-up, also performing cost-utility and cost-benefit analyses. Consecutive, unilateral nAMD patient outcomes for those taking 20mg Zx supplementation orally for ≥ 5years were compared with the Comparison of AMD Treatments Trials (CATT) 5-year historical controls for fellow-eye nAMD conversion. Eleven-year mean life expectancy, cost-utility and cost-benefit models were undertaken employing a 3% discount rate and 2020 US real dollars. Among 227 consecutive patients with nAMD/Zx-supplementation, 202 (90%) had 5-year follow-up. The fellow-eye nAMD 5-year conversion incidence using a Kaplan-Meier cumulative event estimate was 22% (49/227), versus 48% (167/348) with CATT control data (p < 0.0001). An 11-year cost-utility model with estimates for years 6-11 demonstrated a 0.42 (7.7%) QALY (quality-adjusted life-year) gain, including 3months of life saved per patient due to decreased nAMD fellow-eye conversion. This yielded a direct ophthalmic medical cost perspective, incremental cost-utility ratio (CUR) of -$576/QALY and a societal cost perspective CUR of -$125,071/QALY. Zx supplementation for all 2020 US unilateral nAMD cases would have theoretically saved society, primarily patients, $6.0 billion over 11years, a 1531% return on investment (ROI), or 31.3% annual ROI, on Zx costs. Oral zeaxanthin supplementation for unilateral nAMD patients appears to decrease fellow-eye long-term incidence and is cost-effective and financially rewarding. It is dominant vs. no supplementation in patients presenting with unilateral nAMD. ClinicalTrials.gov identifier, NCT01527435.

Study protocol on prevalence of non-exudative macular neovascularisation and its contribution to prediction of exudation in fellow eyes with unilateral exudative AMD (EYE-NEON)

PurposeFellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD) are at risk of developing macular neovascularisation (MNV). These eyes may first develop subclinical non-exudative MNV (neMNV) before they leak to form exudative MNV (eMNV). The EYE NEON study is a 2-year study aimed at estimating the prevalence and incidence of neMNV and evaluating its role as a predictor for conversion to neovascular AMD.MethodsEYE NEON is a multicentre study that will run in retinal clinics across 25 National Health Service with the aim to recruit 800 patients with new onset nAMD in the first eye. The fellow-eye with no evidence of nAMD at baseline will be the study eye. All study eyes will have OCT and OCTA done at first and second year following first anti-VEGF treatment to the first eye (non-study eye), with new onset nAMD. We will estimate the prevalence and incidence of neMNV over 2 years, rate of conversion from neMNV to eMNV and numbers initiated on treatment for neovascular AMD in the study eye will be reported. Predictive models of conversion including neMNV with other demographic and imaging parameters will be developed.ConclusionThe study design with proposed target sample size is sufficient to evaluate the retinal imaging characteristics of the study eyes with and without neMNV and develop predictive models to inform risk of conversion to nAMD.

Consequences of Real-World Surveillance of Fellow Eyes in Neovascular Age-Related Macular Degeneration.

This study investigated whether the interval of monitoring at-risk, fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD) has any bearing on the severity of the disease at the time of diagnosis. The study comprised a retrospective, cross-sectional comparative case series of treatment-naïve eyes in patients who were diagnosed sequentially with nAMD. We compared the visual acuity (VA) and central macular thickness (CMT) of patients who were actively receiving intravitreal injections (IVIs) of anti-vascular endothelial growth factor (anti-VEGF) agents at the time of second eye diagnosis with the VA and CMT of patients who had ceased treatment in their first eye because of reaching end-stages of disease. Intervals of visits and frequency of monitoring the macula of fellow eyes by means of optical coherence tomography (OCT) were abstracted from the medical record. We found that the at-risk fellow eyes of patients who had stopped treatment for nAMD in their first eye prior to fellow eye conversion were monitored significantly less frequently than the fellow eyes of patients who continued to receive treatment at the time of second eye diagnosis. Despite less frequent monitoring, VA and CMT were similar at the time of fellow eye diagnosis for both groups.

Choriocapillaris Flow Imbalance in Fellow Eyes in Age-Related Macular Degeneration.

PurposeThe purpose of this study was to identify early changes in choriocapillaris flow in patients with age-related macular degeneration (AMD) with no history of macular neovascularization (MNV).MethodsClinical records of fellow eyes of patients with unilateral neovascular AMD without fundus findings and control eyes of otherwise healthy individuals, except for mild cataract, diagnosed at St. Luke's International Hospital from April 2020 to March 2021, were retrospectively analyzed. Optical coherence tomography (OCT) angiography images of the choriocapillaris slab were binarized using the Phansalkar local thresholding methods to evaluate the choriocapillaris flow area (CCFA) and its coefficient of variation (CV).ResultsThe data of 24 AMD fellow eyes (17 for men, 71.7 ± 1.9 years old) and 21 control eyes (11 for men, 69.1 ± 2.0 years old) were analyzed. The mean CCFA ratio was lower in the AMD fellow eyes (58.6 ± 1.2%) than in the control eyes (62.4 ± 1.3%, P = 0.032), and the mean CV of CCFA ratio was greater in the AMD fellow eyes (0.174 ± 0.007) than in the control eyes (0.154 ± 0.007, P = 0.032). Eyes with CCFA ratio <60% and CV of CCFA ratio ≥0.154 had a 4.371-fold higher risk of being AMD fellow eyes (95% confidence interval = 1.029–18.56, P = 0.046). Differences in CV of CCFA ratio between AMD fellow eyes and control eyes were particularly clear in eyes with thick choroids (mean CV of CCFA in control versus AMD fellow eyes with central choroidal thickness ≥220 µm: 0.144 ± 0.005 vs. 0.173 ± 0.007, P = 0.009**).ConclusionsNeovascular AMD fellow eyes without MNV had reduced, heterogeneous, and imbalanced choriocapillaris flow, which may constitute early changes in neovascular AMD, although further studies are required.

Chorioretinal thickness and retinal pigment epithelial degeneration of fellow eyes in patients with unilateral neovascular age-related macular degeneration with subretinal drusenoid deposits

BackgroundWe sought to investigate the chorioretinal thickness and retinal pigment epithelial (RPE) degenerative features of eyes with early age-related macular degeneration (AMD) and subretinal drusenoid deposits (SDDs) according to the presence of macular neovascularization (MNV) in the fellow eyes.MethodsWe classified 70 eyes into two groups of 47 eyes with non-neovascular AMD and 23 eyes with neovascular AMD, respectively, according to the presence of MNV in the fellow eyes. The mean macular retinal, ganglion cell–inner plexiform layer (GCIPL), and choroidal thickness values and RPE features of the 6-mm-diameter zone were compared. RPE degeneration was defined as a lesion with an incomplete RPE and outer retinal atrophy (iRORA) or attenuated RPE reflectivity with diffuse basal laminar deposits, which was defined as when the eye showed an attenuated RPE line with granular features and mixed reflectivity in combination with sub-RPE deposits with a lesion ≥ 1,000 µm in length.ResultsMean retinal, GCIPL, and choroidal thickness values (286.69 ± 15.02 µm, 64.36 ± 4.21 µm, and 156.11 ± 33.10 µm) of the neovascular AMD group were greater than those (278.61 ± 13.96 µm, 61.44 ± 4.63 µm, and 133.59 ± 34.33 µm) of the non-neovascular AMD group (all P < 0.05). RPE degeneration was more prevalent in the neovascular AMD group (65.2%) than the non-neovascular AMD group (38.3%; P = 0.034). Greater mean GCIPL and choroidal thickness values and the presence of RPE degeneration were associated with type 3 MNV in fellow eyes (all P < 0.05).ConclusionsDifferent degenerative features according to MNV in fellow eyes of patients with AMD and SDDs suggest that variable degenerative features might be present during disease progression and have an association with the phenotype.

Non-invasive testing for early detection of neovascular macular degeneration in unaffected second eyes of older adults: EDNA diagnostic accuracy study.

Neovascular age-related macular degeneration is a leading cause of sight loss, and early detection and treatment is important. For patients with neovascular age-related macular degeneration in one eye, it is usual practice to monitor the unaffected eye. The test used to diagnose neovascular age-related macular degeneration, fundus fluorescein angiography, is an invasive test. Non-invasive tests are available, but their diagnostic accuracy is unclear. The primary objective was to determine the diagnostic monitoring performance of tests for neovascular age-related macular degeneration in the second eye of patients with unilateral neovascular age-related macular degeneration. The secondary objectives were the cost-effectiveness of tests and to identify predictive factors of developing neovascular age-related macular degeneration. This was a multicentre, prospective, cohort, comparative diagnostic accuracy study in a monitoring setting for up to 3 years. A Cox regression risk prediction model and a Markov microsimulation model comparing cost-effectiveness of the index tests over 25 years were used. This took place in hospital eye services. Participants were adults (aged 50-95 years) with newly diagnosed (within the previous 6 weeks) neovascular age-related macular degeneration in one eye and an unaffected second (study) eye who were attending for treatment injections in the first eye and who had a study eye baseline visual acuity of ≥ 68 Early Treatment Diabetic Retinopathy Study letters. The index tests were Amsler chart (completed by participants), fundus clinical examination, optical coherence tomography, self-reported vision assessment (completed by participants) and visual acuity. The reference standard was fundus fluorescein angiography. The main outcome measures were sensitivity and specificity; the performance of the risk predictor model; and costs and quality-adjusted life-years. In total, 552 out of 578 patients who consented from 24 NHS hospitals (n = 16 ineligible; n = 10 withdrew consent) took part. The mean age of the patients was 77.4 years (standard deviation 7.7 years) and 57.2% were female. For the primary analysis, 464 patients underwent follow-up fundus fluorescein angiography and 120 developed neovascular age-related macular degeneration on fundus fluorescein angiography. The diagnostic accuracy [sensitivity (%) (95% confidence interval); specificity (%) (95% confidence interval)] was as follows: optical coherence tomography 91.7 (85.2 to 95.6); 87.8 (83.8 to 90.9)], fundus clinical examination [53.8 (44.8 to 62.5); 97.6 (95.3 to 98.9)], Amsler [33.7 (25.1 to 43.5); 81.4 (76.4 to 85.5)], visual acuity [30.0 (22.5 to 38.7); 66.3 (61.0 to 71.1)] and self-reported vision [4.2 (1.6 to 9.8); 97.0 (94.6 to 98.5)]. Optical coherence tomography had the highest sensitivity across all secondary analyses. The final prediction model for neovascular age-related macular degeneration in the non-affected eye included smoking status, family history of neovascular age-related macular degeneration, the presence of nodular drusen with or without reticular pseudodrusen, and the presence of pigmentary abnormalities [c-statistic 0.66 (95% confidence interval 0.62 to 0.71)]. Optical coherence tomography monitoring generated the greatest quality-adjusted life-years gained per patient (optical coherence tomography, 5.830; fundus clinical examination, 5.787; Amsler chart, 5.736, self-reported vision, 5.630; and visual acuity, 5.600) for the lowest health-care and social care costs (optical coherence tomography, £19,406; fundus clinical examination, £19,649; Amsler chart, £19,751; self-reported vision, £20,198; and visual acuity, £20,444) over the lifetime of the simulated cohort. Optical coherence tomography dominated the other tests or had an incremental cost-effectiveness ratio below the accepted cost-effectiveness thresholds (£20,000) across the scenarios explored. The diagnostic performance may be different in an unselected population without any history of neovascular age-related macular degeneration; the prediction model did not include genetic profile data, which might have improved the discriminatory performance. Optical coherence tomography was the most accurate in diagnosing conversion to neovascular age-related macular degeneration in the fellow eye of patients with unilateral neovascular age-related macular degeneration. Economic modelling suggests that optical coherence tomography monitoring is cost-effective and leads to earlier diagnosis of and treatment for neovascular age-related macular degeneration in the second eye of patients being treated for neovascular age-related macular degeneration in their first eye. Future works should investigate the role of home monitoring, improved risk prediction models and impact on long-term visual outcomes. This study was registered as ISRCTN48855678. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 8. See the NIHR Journals Library website for further project information.

Ganglion Cell Layer Thickness Change in Neovascular Age-Related Macular Degeneration Treated With Anti-VEGF Injections.

This work assesses bilateral ganglion cell layer-inner plexiform layer (GCL-IPL) thickness changes in patients with unilateral neovascular age-related macular degeneration (nAMD) treated with antivascular endothelial growth factor (anti-VEGF). In this single-center, retrospective, cohort study, the medical records of patients with unilateral nAMD treated with anti-VEGF were reviewed. The treated group included eyes with newly diagnosed nAMD that subsequently underwent treatment with intravitreal anti-VEGF injections. The control group was the fellow eye with dry AMD. Eyes receiving at least 10 intravitreal injections were included. Measurement of GCL-IPL thickness was performed at different time points using spectral domain-optical coherence tomography. A total of 216 eyes of 108 patients met the inclusion criteria. The mean age ± SD was 80.1 ± 10.7 years. Eyes in the treated group underwent a mean ± SD of 20.2 ± 7.2 injections in 21.3 ± 6.8 months. At baseline, average mean ± SD of GCL-IPL thickness was 73.71 ± 8.81 µm and 73.84 ± 8.26 µm in the treated and fellow eye, respectively (P = .795). After 10 injections the average thickness was 65.41 ± 14.08 µm and 68.77 ± 13.24 µm in the treated and fellow eye, respectively (P = .007). The absolute decrease in thickness was significantly greater in the treated eye than the fellow eye (mean ± SD, 8.31 ± 11.19 µm vs 5.07 ± 10.83 µm, respectively; P = .002). GCL-IPL thickness decreased significantly in the treated group more than in the control group after 10 anti-VEGF injections. The mechanism and clinical significance of this observation warrants further study.

Diagnostic Accuracy of Monitoring Tests of Fellow Eyes in Patients with Unilateral Neovascular Age-Related Macular Degeneration: Early Detection of Neovascular Age-Related Macular Degeneration Study

PurposeTo evaluate the diagnostic accuracy of routinely used tests of visual function and retinal morphology compared with fundus fluorescein angiography (FFA) to detect onset of active macular neovascularization in unaffected fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD).DesignProspective diagnostic accuracy cohort study conducted in 24 eye clinics in the United Kingdom over 3 years.ParticipantsOlder adults (>50 years) with recently diagnosed unilateral nAMD with a fellow (study) eye free of nAMD.MethodsSelf-reported vision, Amsler, clinic-measured visual acuity (VA), fundus assessment, and spectral domain OCT. The reference standard is FFA.Main Outcome MeasuresSensitivity and specificity of the 5 index tests.ResultsOf 552 participants monitored for up to 3 years, 145 (26.3%) developed active nAMD in the study eye, of whom 120 had an FFA at detection and constituted the primary analysis cohort. Index test positives at nAMD detection in those confirmed by FFA were self-reported vision much worse (5), distortion on Amsler (33), 10-letter decrease in acuity from baseline (36), fundus examination (64), and OCT (110). Percentage index test sensitivities were: self-reported vision 4.2 (95% confidence interval [CI], 1.6–9.8); Amsler 33.7 (95% CI, 25.1–43.5); VA 30.0 (95% CI, 22.5–38.7); fundus examination 53.8 (95% CI, 44.8–62.5); and OCT 91.7 (95% CI, 85.2–95.6). All 5 index test specificities were high at 97.0 (95% CI, 94.6–98.5), 81.4 (95% CI, 76.4–85.5), 66.3 (95% CI, 61.0–71.1), 97.6 (95% CI, 95.3–98.9), and 87.8 (95% CI, 83.8–90.9), respectively. The combination of OCT with one other index test that was a secondary outcome measure increased sensitivity marginally and decreased specificity for all combinations except fundus examination.ConclusionsTests of self-reported change in vision, unmasking of new distortion, measurements of acuity, and fundus checks to diagnose active nAMD performed poorly in contrast to OCT. Our findings support a change to guidelines in clinical practice to monitor for onset of nAMD.

Changes in the Ganglion Cell-inner Plexiform Layer after Consecutive Intravitreal Injections of Anti-vascular Endothelial Growth Factor in Age-related Macular Degeneration Patients.

PurposeTo investigate the effect of intravitreal anti-vascular endothelial growth factor (VEGF) injections on ganglion cell-inner plexiform layer (GCIPL) thickness in patients with age-related macular degeneration (AMD).MethodsThis retrospective study included patients with continuous anti-VEGF treatment who were administered at least three consecutive injections for unilateral neovascular AMD. The GCIPL thickness of the study eyes was compared before and after treatment and with healthy fellow eyes using spectral-domain optical coherence tomography. We also evaluated best-corrected visual acuity, age, and intraocular pressure.ResultsIn total, 96 eyes of 48 patients (14 females and 34 males; mean ± standard deviation [SD] age, 70.10 ± 8.89 years) with mean number of 6.29 (SD ± 3.76) anti-VEGF injections and a mean follow-up period of 24.93 months (SD ± 19.86) were included in the study. After three consecutive intravitreal injections of anti-VEGF, the mean GCIPL thickness was significantly reduced from 70.50 (SD ± 14.06) to 65.97 (SD ± 13.91) µm. Borderline or nonsignificant decrease was also observed in GCIPL thickness for each sector. At the end of the study, the mean GCIPL thickness was further reduced to 62.56 (SD ± 16.30) µm, and significant decreases were also observed in all other sectors compared with baseline.ConclusionsIt has been observed that GCIPL thickness can decrease with only three consecutive anti-VEGF injections as well as with long-term treatment in AMD patients.

Longitudinal Changes in Ganglion Cell–Inner Plexiform Layer of Fellow Eyes in Unilateral Neovascular Age-Related Macular Degeneration

To determine longitudinal changes in the ganglion cell-inner plexiform layer (GC-IPL) thickness of the fellow eyes of patients with neovascular age-related macular degeneration (AMD). Prospective cohort study. Patients with unilateral neovascular AMD, unilateral polypoidal choroidal vasculopathy (PCV), and control subjects were included. After the initial visit, GC-IPL thickness was measured twice more with at least a 1-year interval between examinations using spectral domain optical coherence tomography. Twenty-seven fellow eyes of patients with unilateral choroidal neovascularization (CNV), 33 fellow eyes of patients with unilateral PCV, and 35 eyes of control subjects were enrolled. The GC-IPL thickness of the fellow eyes was 78.41 ± 9.23, 81.20 ± 5.52, and 81.60 ± 3.83μm in the CNV, PCV, and control groups, respectively, and they showed a significant change over time (P< .001, P= .001, and P= .003, respectively). The reduction rate of GC-IPL thickness was-0.88,-0.41, and-0.31μm per year in the fellow eyes of the CNV, PCV, and control groups, respectively (CNV > PCV, control, P < .001). In a linear mixed model determination of factors associated with GC-IPL reduction in the fellow eyes of the CNV group, the interaction between baseline GC-IPL thickness and duration showed a significant result (P < .001). The fellow eyes of patients with neovascular AMD showed a greater reduction rate of GC-IPL thickness compared with fellow eyes of patients with unilateral PCV and control subjects. In patients with unilateral neovascular AMD, fellow eyes with a thicker GC-IPL at baseline showed a greater reduction in GC-IPL thickness over time.

Optical coherence tomography angiography findings of the fellow eye of patients with unilateral neovascular age-related macular degeneration OCT-A Evaluation of Fellow Eyes of CNV

Purpose. Age related macular degeneration (ARMD) remains a serious cause of vision loss in elderly people worldwide. The purpose of the study is to investigate the fellow eye of the patients with exudative ARMD using optical coherence tomography angiography (OCTA). Methods. We conducted a retrospective study from the data of patients with exudative ARMD. Patients undergoing intravitreal anti-VEGF treatment for one eye were selected. OCTA images of both eyes with choroidal neovascularization (CNV) and the fellow eyes were evaluated retrospectively. Midchoroid, choriocapillaris (CC), retina pigment epithelium (RPE), and outer retina levels were evaluated using RTVue XR AVANTI OCTA. Results. There were 5 male and 5 female patients included in this study. We detected drusen and pigment epithelial detachments (PED) in fellow eyes. Six fellow eyes had vascularized PED. Four of them were acute flat irregular type; two of them were chronic dome shaped type. Four patients had soft drusen that had shown signal loss on choriocapillaris level. Conclusion. The follow-up of both eyes of the patients with ARMD is very important. OCTA seems a promising non-invasive method in order to detect subclinical early stage CNV and distinguish among types of PEDs.

Neovascularization in Fellow Eye of Unilateral Neovascular Age-related Macular Degeneration According to Different Drusen Types

To investigate the incidence of fellow eye (FE) neovascular age-related macular degeneration (nAMD) in patients with unilateral nAMD according to FE drusen type. Retrospective cohort study. Between January 2013 and June 2016, 434 consecutive patients with naïve nAMD were enrolled. We selected 280 eligible patients with treatment-naïve, unilateral nAMD for analysis (280/280= 100% patients were followed up at 2 years; 50/280= 17.9% patients were followed up at 5 years). The incidence and hazard ratios (HR) of FE nAMD according to age, sex, choroidal thickness, nAMD subtype, and drusen type were analyzed. The 5-year incidence of FE nAMD was 20.9%. The incidences of the soft plus subretinal drusenoid deposits (SDD), soft drusen only, and SDD only groups were 76.4%, 46.2%, and 25.7%, respectively; they were significantly higher than the no drusen group (vs 3.6%; P < .001, P < .001, P < .001). There was no significant difference between the pachydrusen and no drusen groups (7.1% vs 3.6%; P= .101). The multivariate Cox regression hazard model revealed older age (HR, 1.053; P= .031) and drusen type were significant (P= .001). Compared with the no drusen group, the soft drusen plus SDD, soft drusen only, and SDD groups showed an HR of 18.460 (P= .001), 8.302 (P= .015), and 5.465 (P= .082), respectively. Pachydrusen was not shown to be a significant risk factor compared to the no drusen group (HR, 2.417; P= .281). The incidence of FE nAMD was significantly different with respect to drusen type. Soft drusen plus SDD had the highest risk of neovascular AMD, followed by soft drusen only and SDD only.

Progression of subclinical choroidal neovascularization in age-related macular degeneration.

PurposeTo use optical coherence tomography angiography (OCTA) to study longitudinal subclinical choroidal neovascularization (CNV) changes and their correlation with progression to exudation in age-related macular degeneration (AMD).MethodsThis study included a total of 34 patients with unilateral neovascular AMD who were evaluated prospectively using OCTA to detect subclinical CNV in their fellow eye. Eyes with baseline subclinical CNV were followed with serial OCTA for a minimum of one year (15.2±3.27 months) to monitor the development of exudation.ResultsOf the 34 fellow eyes studied, five were found to have baseline subclinical CNV. One of the five cases of baseline subclinical CNV converted to exudative AMD during the follow up period. The average surface area of baseline subclinical CNV on OCTA was 0.131±0.096 mm2 which progressed to 0.136±0.104 mm2 at the final follow up (P = 0.539). Geographic atrophy grew at a rate of 0.82±1.20mm2/year in four eyes without subclinical CNV and 0.02mm2/year in one eye with subclinical CNV.Conclusion and importanceThe rate of conversion to exudative AMD in eyes with subclinical CNV of 20% in our study is similar to previous reports and suggests the importance of vigilance in these eyes. The lower growth rate of geographic atrophy may suggest a protective effect of subclinical CNV that deserves further study.

Short‐term effect on the ocular circulation induced by unilateral intravitreal injection of aflibercept in age‐related maculopathy

PurposeIntravitreal injection of anti‐vascular endothelial growth factor (anti‐VEGF) is the standard treatment for neovascular age‐related macular degeneration (AMD). As VEGF is a physiological key player for regulating retinal vascular tone, questions have been raised whether the application of anti‐VEGF could induce alterations in ocular perfusion.MethodsThe study included 20 eyes from 20 Caucasian patients with unilateral neovascular AMD and 20 fellow eyes. All eyes were treated with standard intravitreal injection of aflibercept (IVA). Measurements of blood flow at the optic nerve head (ONH) and the choroid were performed with laser speckle flowgraphy (LSFG). The intraocular pressure (IOP), systolic and diastolic blood pressure, heart rate, mean arterial pressure (MAP) and ocular perfusion pressure (OPP) were analysed. Measurements were performed at baseline and repeated immediately after the injection and 30 and 45 min later.ResultsMean time between injection of aflibercept and first follow‐up was 8:56 ± 4:25 min. The injection led to significant rise in IOP. In the injected eyes, mean blur rate (MBR, i.e. a relative measure of perfusion and the main outcome parameter of LSFG) within the major vessels of the ONH as well as at the entire ONH region decreased significantly (p < 0.001). No change in MBR was observed in the fellow eye. Choroidal blood flow was maintained stable in both eyes.ConclusionIntravitreal injection of aflibercept (IVA) led to a short‐term reduction in perfusion only in the treated eye. This was independent from IOP, indicating a direct pharmacological effect. No changes in choroidal perfusion were observed during the first 45 min after the injection.

Fundus autofluorescence and retinal sensitivity in fellow eyes of age-related macular degeneration in Japan.

PurposeAbnormal fundus autofluorescence (FAF) potentially precedes onset of late age-related macular degeneration (AMD) in Caucasian patients. Many differences exist between Asian and Caucasian patients regarding AMD types and severity, gender, and genetic backgrounds. We investigated the characteristics of abnormal FAF and retinal sensitivity in the fellow eyes of Japanese patients with unilateral neovascular AMD.MethodsSixty-six patients with unilateral neovascular AMD and abnormal FAF in the fellow eye were enrolled in this multicenter, prospective, observational study. The best-corrected visual acuity, fundus photographs, FAF images, and retinal sensitivity on microperimetry were measured periodically for 12 months. The FAF images were classified into eight patterns based on the International Fundus Autofluorescence Classification Group. The points measured by microperimetry were superimposed onto the FAF images and fundus photographs and classified as “within,” “close,” and “distant,” based on the distance from the abnormal FAF and other findings. The relationship between the location of the baseline abnormal FAF and retinal sensitivity was investigated.ResultsIn Japanese patients, patchy (33.3%) and focally increased (30.3%) patterns predominated in the abnormal FAF. Intermediate-to-large drusen was associated predominantly with hyperfluorescence and hypofluorescence. Neovascular AMD developed within 1 year in six (9.1%) eyes, the mean baseline retinal sensitivity of which was 12.8 ± 4.7 dB, significantly (p<0.002) lower than the other eyes. In 44 of the other 60 eyes, microperimetry was measurable at baseline and month 12 and the mean retinal sensitivity improved significantly from 13.5 ± 4.4 to 13.9 ± 4.8 dB (p<0.001), possibly associated with lifestyle changes (e.g., smoking cessation, antioxidant and zinc supplementation). The mean retinal sensitivities of points within and close to the abnormal FAF were 9.9 and 11.7 dB, respectively, which were significantly lower than the 14.0 dB of the points distant from the abnormal FAF.ConclusionIn Japanese patients, patchy and focally increased patterns predominated in the abnormal FAF. The retinal sensitivity was lower close to/within the abnormal FAF. FAF and microperimetry are useful to assess macular function before development of neovascular AMD or geographic atrophy.

Variation of Retinal and Choroidal Vasculatures in Patients With Age-Related Macular Degeneration

To investigate variations in chorioretinal vasculatures in fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD). We included fellow eyes of consecutive patients with unilateral nAMD from swept source optical coherence tomography (SS-OCT) angiography database. Vascular and nonvascular indices were determined based on SS-OCT and SS-OCT angiography images. Variation of the vascular or nonvascular index was compared between fellow eyes with and without early AMD. In 146 fellow eyes, 88 (60.3%) had early AMD and 58 (39.7%) had a normal fundus. Vascular density (VD) values of the superficial and deep retinal capillary plexus and choriocapillaris were smaller in eyes with early AMD than in those without (P < 0.001, P = 0.001, P = 0.006, respectively). Flow void area in choriocapillaris was greater in eyes with early AMD than those without (P = 0.015). In 88 fellow eyes with early AMD, vascular indices of the retina were correlated with those of choroid while nonvascular indices were not. Fellow eyes of patients with classic exudative AMD had greater foveal avascular zone area and smaller VD values of the deep retinal capillary plexus than those with polypoidal choroidal vasculopathy (P < 0.001, P = 0.004). In addition to vascular insufficiency in the choroid or choriocapillaris, retinal vascular alteration was apparent in eyes with early AMD. It may suggest that retinal vessels were involved in the pathogenesis of AMD even while changes in nonvascular components of the retina were not yet apparent.

Changes in Retinal Layer Thickness in the Contralateral Eye of Patients with Unilateral Neovascular Age-Related Macular Degeneration

To evaluate the thickness of the outer retinal layers and its relationship with visual function in fellow eyes of participants with unilateral neovascular age-related macular degeneration (AMD). Longitudinal study. We enrolled 105 subjects with unilateral neovascular AMD from 3 clinical centers in Europe. The fellow eye, without advanced AMD, was selected for the study. Subjects were followed up with visits occurring every 6 months for 2 years. Spectral domain optical coherence tomography volume scans were collected at 3 clinical sites, in Belfast, Northern Ireland; Coimbra, Portugal; and Milan, Italy. Detailed manual segmentation of outer retinal layers was performed using the custom-designed and validated grading software 3D OCTOR. Thickness measurements for neurosensory retina, photoreceptor layer (PRL) outer segments, retinal pigment epithelium plus drusen (RPE+drusen) complex, and choroidal layers from each sector of the standard macular grid were obtained. Measures of vison were distance visual acuity, near visual acuity, Smith-Kettlewell Institute low-luminance acuity score, and reading speed. Subjects were grouped based on the presence or absence of subretinal drusenoid deposits (SDDs) for further analysis. Change in thickness of retinal layers and change in measures of vision. In all, 85 eyes were included in the analysis. The average duration of follow-up was 20.5 ± 5.8 months. By the final visit, the RPE+drusen complex was significantly thinner when compared with baseline (29.7 μm vs. 34.09 μm; P= 0.03). Low-luminance deficit was significantly worse at the final visit (P < 0.001) and correlated with PRL outer segment thickness (r= 0.33; P=0.02). The RPE+drusen complex was significantly thicker in eyes with SDDs compared with that in those without SDDs (30.67 μm vs. 28.64 μm; P= 0.02). PRL outer segments became significantly thinner over time in eyes with SDDs compared with those in eyes without SDDs. The RPE+drusen complex layer becomes thinner over time in fellow eyes of subjects with unilateral neovascular AMD. The rate of PRL outer segment thinning was higher in eyes with SDDs than in eyes without SDDs. These findings are preliminary steps in the identification of early biomarkers for detecting and monitoring the progression of AMD.

Cost-effectiveness of age-related macular degeneration study supplements in the UK: combined trial and real-world outcomes data

AimsTo evaluate the cost-effectiveness of Age-Related Eye Disease Study (AREDS) 1 & 2 supplements in patients with either bilateral intermediate age-related macular degeneration, AREDS category 3, or unilateral neovascular age-related...

A genome-wide association study identified a novel genetic loci STON1-GTF2A1L/LHCGR/FSHR for bilaterality of neovascular age-related macular degeneration

Bilateral neovascular age-related macular degeneration (AMD) causes much more handicaps for patients than unilateral neovascular AMD. Although several AMD-susceptibility genes have been evaluated for their associations to bilaterality, genome-wide association study (GWAS) on bilaterality has been rarely reported. In the present study, we performed GWAS using neovascular AMD cases in East Asian. The discovery stage compared 581,252 single nucleotide polymorphisms (SNPs) between 803 unilateral and 321 bilateral Japanese cases but no SNP showed genome-wide significance, while SNPs at six regions showed P-value < 1.0 × 10−5, STON1-GTF2A1L/LHCGR/FSHR, PLXNA1, CTNNA3, ARMS2/HTRA1, LHFP, and FLJ38725. The first replication study for these six regions comparing 36 bilateral and 132 unilateral Japanese cases confirmed significant associations of rs4482537 (STON1-GTF2A1L/LHCGR/FSHR), rs2284665 (ARMS2/HTRA1), and rs8002574 (LHFP) to bilaterality. In the second replication study comparing 24 bilateral and 78 unilateral cases from Singapore, rs4482537 (STON1-GTF2A1L/LHCGR/FSHR) only showed significant association. Meta-analysis of discovery and replication studies confirmed genome-wide level significant association (P = 2.61 × 10−9) of rs4482537 (STON1-GTF2A1L/LHCGR/FSHR) and strong associations (P = 5.76 × 10−7 and 9.73 × 10−7, respectively) of rs2284665 (ARMS2/HTRA1) and rs8002574 (LHFP). Our GWAS for neovascular AMD bilaterality found new genetic loci STON1-GTF2A1L/LHCGR/FSHR and confirmed the previously reported association of ARMS2/HTRA1.

Visual function quality of life measure changes upon conversion to neovascular age-related macular degeneration in second eyes.

To determine changes in quality of life measures when choroidal neovascularization (CNV) developed in the second eye of patients with initially unilateral neovascular age-related macular degeneration (AMD). We analyzed responses to the 39-item National Eye Institute Visual Function Questionnaire (NEI-VFQ), 36-item Short Form Health Survey (SF-36), and Hospital Anxiety and Depression Scale (HADS) at baseline, and prior to and following second eye CNV diagnosis in 92 participants enrolled in two Submacular Surgery Trials. Paired t-tests for sample sizes over 30 and Wilcoxon signed-rank tests for sample sizes <30 were performed to compare scores. CNV development resulted in statistically and clinically significant changes in responses to 20 of 39 NEI-VFQ items, indicating visual function decline during a mean interval of 25 months. Little difference was noted between baseline scores and prior to CNV diagnosis, which averaged 8.9 months duration. Subscales demonstrated a statistically significant decline in general vision, near activities, distance activities, social functioning, role difficulties, dependency, and driving. There were minimal changes in the HADS and SF-36 scales. CNV development in the second eye had a dramatic effect on visual functioning based on patient responses to the NEI-VFQ questionnaire. Our investigation is believed to be the first study using data collected prospectively to demonstrate vision-related quality of life changes that resulted from development of CNV in AMD patients.