Polypoidal Choroidal Vasculopathy in Caucasians: Morphological Findings from Multimodal Retinal Imaging.

PURPOSE: The aim of the study was to characterize the morphological features of polypoidal choroidal vasculopathy (PCV) in a large Caucasian population. METHODS: We conducteda multicenter, cross-sectional study of treatment-naïve patients with PCV. Baseline fundus photography, spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography (FA), and indocyanine green angiography (ICGA) were assessed by trained medical graders. Typical PCV features were explored, and retinal thickness (RT) and choroidal thickness (CT) measurements were performed. RESULTS: Seventy-nine eyes of 73 patients (mean age, 72.6 ± 11.9 years) were included. ICGA identified macular polyps in 89.9% of cases. SD-OCT revealed mostly subretinal fluid (93.6%) and a retinal pigment epithelium (RPE) detachment in 91.4%, with sharp protrusion in 67.0% of cases. Polyp-like structures were seen in 74.3% of cases, mostly adherent to an elevated RPE (69.6%). Type 1 neovascularization (NV) was identified in 74.7% of patients, while 16.5% had a mixed NV. The mean macular CT was 220.9 ± 83.2 µm (range, 67.9-403.6). Diffuse and focal pachychoroid were observed in 26.6 and 30.4% of patients, respectively. Soft drusen were reported in 62.0% of cases, but retinal hemorrhage occurred in only 19.0% of cases. CONCLUSION: The morphological features of PCV in Caucasians are similar to those reported in Asians. Pachychoroid signs were found in nearly half of our cohort. However, the mean age at presentation, high prevalence of soft drusen, and low prevalence of large subretinal hemorrhages make PCV closer to age-related macular degeneration in this ethnic group.

Peripapillary and macular morpho-vascular changes in patients with genetic or clinical diagnosis of autosomal dominant optic atrophy: a case-control study.

PURPOSE: To evaluate the macular and peripapillary morpho-vascular changes in ADOA, using optical coherence tomography (OCT) and OCT angiography (OCTA). METHODS: Prospectively defined, cross-sectional case-control study. Consecutive patients with a genetic or clinical diagnosis of ADOA along with age- and sex-matched controls were included. The radial peripapillary capillary (RPC) density and vessel density (VD) in the parafoveal superficial and deep capillary plexuses (SCP and DCP, respectively) were evaluated with OCTA. The ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL) thickness were determined using structural OCT. We applied a previously validated customized macro (Fiji, SciJava Consortium) to compute RPC density. The remaining parameters were calculated by the built-in software. Non-parametric methods were used for data analysis. The target α level was 0.05, which was adjusted through Bonferroni's correction when multiple outcomes were tested. RESULTS: Fifty-eight eyes (n = 29 control; n = 29 ADOA) from 30 subjects (mean age 42.43 ± 15.30 years; 37.93% male) were included. Parafoveal SCP VD, GCC thickness, RPC VD in the temporal quadrant, as well as RNFL thickness in the nasal and temporal quadrants were decreased in ADOA eyes (all p < 0.001). When only patients with genetically confirmed diagnosis were included, capillary dropout in the circumpapillary superior and inferior quadrants also became evident (both p < 0.001). The GCC/parafoveal SCP ratio was increased in ADOA, relatively to matched controls. In contrast, none of the circumpapillary morpho-vascular ratios was significantly different in ADOA eyes. CONCLUSIONS: The microvascular and structural changes found in ADOA suggest that both the macular and peripapillary regions are involved, although the threshold for damage of the structural and vascular components may be different for each region. Larger series with longitudinal follow-up may validate OCTA biomarkers helpful for disease monitoring.

PERIPAPILLARY NEUROVASCULAR COUPLING IN THE EARLY STAGES OF DIABETIC RETINOPATHY.

PURPOSE: To study radial peripapillary capillary (RPC) density in the early stages of diabetic retinopathy (DR), using optical coherence tomography angiography. METHODS: A cross-sectional evaluation of RPCs was performed using optical coherence tomography angiography (Avanti RTVue-XR 100, Optovue Inc, Fremont, CA). Annular RPC density was the primary outcome. Global density and retinal nerve fiber layer thickness were secondary outcomes. Diabetic eyes were divided into three groups: no DR, mild nonproliferative DR (mild NPDR), and moderate NPDR. Multilevel mixed-effects univariate and multivariate linear regression models were used. RESULTS: We included 155 eyes (n = 42 control; n = 27 no DR; n = 28 mild NPDR; and n = 58 moderate NPDR) from 86 subjects (mean [SD] age 63.39 [10.70] years; 46.45% male). When compared with controls, a significant decrease in annular RPC density was found in all groups of diabetic eyes on multivariate analysis (no DR: ß = -2.95, P < 0.001; mild NPDR: ß = -1.76, P = 0.017; and moderate NPDR: ß = -2.82, P < 0.001). We also detected a significant decrease in retinal nerve fiber layer thickness in diabetic eyes (even in the no DR group). Furthermore, in diabetic eyes, annular RPC density and retinal nerve fiber layer thickness correlated significantly (R = 0.4874, P < 0.001). CONCLUSION: Peripapillary neurovascular changes occur early in the course of DR. Their significance in the progression of DR warrants further research.

Human Plasma Metabolomics Study across All Stages of Age-Related Macular Degeneration Identifies Potential Lipid Biomarkers.

PURPOSE: To characterize the plasma metabolomic profile of patients with age-related macular degeneration (AMD) using mass spectrometry (MS). DESIGN: Cross-sectional observational study. PARTICIPANTS: We prospectively recruited participants with a diagnosis of AMD and a control group (>50 years of age) without any vitreoretinal disease. METHODS: All participants underwent color fundus photography, used for AMD diagnosis and staging, according to the Age-Related Eye Disease Study classification scheme. Fasting blood samples were collected and plasma was analyzed by Metabolon, Inc. (Durham, NC), using ultrahigh-performance liquid chromatography (UPLC) and high-resolution MS. Metabolon's hardware and software were used to identify peaks and control quality. Principal component analysis and multivariate regression were performed to assess differences in the metabolomic profiles of AMD patients versus controls, while controlling for potential confounders. For biological interpretation, pathway enrichment analysis of significant metabolites was performed using MetaboAnalyst. MAIN OUTCOME MEASURES: The primary outcome measures were levels of plasma metabolites in participants with AMD compared with controls and among different AMD severity stages. RESULTS: We included 90 participants with AMD (30 with early AMD, 30 with intermediate AMD, and 30 with late AMD) and 30 controls. Using UPLC and MS, 878 biochemicals were identified. Multivariate logistic regression identified 87 metabolites with levels that differed significantly between AMD patients and controls. Most of these metabolites (82.8%; n = 72), including the most significant metabolites, belonged to the lipid pathways. Analysis of variance revealed that of the 87 metabolites, 48 (55.2%) also were significantly different across the different stages of AMD. A significant enrichment of the glycerophospholipids pathway was identified (P = 4.7 × 10-9) among these metabolites. CONCLUSIONS: Participants with AMD have altered plasma metabolomic profiles compared with controls. Our data suggest that the most significant metabolites map to the glycerophospholipid pathway. These findings have the potential to improve our understanding of AMD pathogenesis, to support the development of plasma-based metabolomics biomarkers of AMD, and to identify novel targets for treatment of this blinding disease.

Functional Magnetic Resonance Imaging to Assess the Neurobehavioral Impact of Dysphotopsia with Multifocal Intraocular Lenses.

PURPOSE: To investigate the association between dysphotopsia and neural responses in visual and higher-level cortical regions in patients who recently received multifocal intraocular lens (IOL) implants. DESIGN: Cross-sectional study. PARTICIPANTS: Thirty patients 3 to 4 weeks after bilateral cataract surgery with diffractive IOL implantation and 15 age- and gender-matched control subjects. METHODS: Functional magnetic resonance imaging (fMRI) was performed when participants viewed low-contrast grating stimuli. A light source surrounded the stimuli in half of the runs to induce disability glare. Visual acuity, wavefront analysis, Quality of Vision (QoV) questionnaire, and psychophysical assessment were performed. MAIN OUTCOME MEASURES: Cortical activity (blood oxygen level dependent [BOLD] signal) in the primary visual cortex and in higher-level brain areas, including the attention network. RESULTS: When viewing low-contrast stimuli under glare, patients showed significant activation of the effort-related attention network in the early postoperative period, involving the frontal, middle frontal, parietal frontal, and postcentral gyrus (multisubject random-effects general linear model (GLM), P < 0.03). In contrast, controls showed only relative deactivation (due to lower visibility) of visual areas (occipital lobe and middle occipital gyrus, P < 0.03). Patients also had relatively stronger recruitment of cortical areas involved in learning (anterior cingulate gyrus), task planning, and solving (caudate body). Patients reporting greater symptoms induced by dysphotic symptoms showed significantly increased activity in several regions in frontoparietal circuits, as well as cingulate gyrus and caudate nucleus (q < 0.05). We found no correlation between QoV questionnaire scores and optical properties (total and higher order aberration, modulation transfer function, and Strehl ratio). CONCLUSIONS: This study shows the association between patient-reported subjective difficulties and fMRI outcomes, independent of optical parameters and psychophysical performance. The increased activity of cortical areas dedicated to attention (frontoparietal circuits), to learning and cognitive control (cingulate), and to task goals (caudate) likely represents the beginning of the neuroadaptation process to multifocal IOLs.

Photorefractive keratectomy for myopia and myopic astigmatism correction using the WaveLight Allegretto Wave Eye-Q excimer laser system.

To analyze photorefractive keratectomy (PRK) outcomes in myopia and myopic astigmatism correction using the WaveLight Allegretto Wave Eye-Q(®) excimer laser system (WaveLight Laser Technologie AG, Erlangen, Germany). 222 eyes of 151 patients underwent PRK (mean age 33.5 ± 6.8 years). Pre-operative best spectacle-corrected visual acuity (BSCVA) ranged from 0.4 to -0.1 logMAR (mean -0.03 ± 0.06). Mean spherical equivalent (SE) was -3.29 ± 1.20 D. Efficacy, predictability and safety were evaluated. Minimum follow-up was 3 months. Accountability at 3 and 6 months was 100 and 54 %, respectively (median follow-up 5 months, mean 5.2 ± 2.6 months). At 3 months, mean uncorrected visual acuity (UCVA) was -0.02 ± 0.07 logMAR, BSCVA -0.03 ± 0.05 logMAR, efficacy index 0.98 and safety index 1.02. UCVA was ≥20/16 in 40.1 %, ≥20/20 in 86.5 % and ≥20/25 in 98.2 %. Mean SE was -0.02 ± 0.20 D. Residual refractive error was ± 0.13 D in 81.5 %, ± 0.25 D in 88.7 % and ± 0.50 D in 97.7 %. At 6 months, outcomes were similar: mean UCVA was -0.02 ± 0.07 logMAR, BSCVA -0.03 ± 0.06 logMAR, efficacy index 1.00 and safety index 1.03. UCVA was ≥20/16 in 43.7 %, ≥20/20 in 86.6 % and ≥20/25 in 96.6 %. Mean SE was -0.02 ± 0.17 D. Residual refractive error was ± 0.13 D in 86.6 %, ± 0.25 D in 93.3 % and ± 0.50 D in 98.3 %. Refractive stability was achieved at 3 months. No patient lost more than one line of BSCVA. There were no retreatments. The WaveLight Allegretto Wave Eye-Q is effective, predictable and safe in low-to-moderate myopia and myopic astigmatism PRK correction.

The influence of personality on the quality of vision after multifocal intraocular lens implantation.

OBJECTIVE: To assess the possible correlation between patients' personality traits and subjective perception of quality of vision (QoV), after multifocal intraocular lens (mIOL) implantation. METHODS: patients who had bilateral implantation of a non-diffractive X-WAVE or a trifocal lens were assessed 6 months postoperatively. Patients answered the NEO-Five Factor Inventory (NEO-FFI-20) questionnaire ("Big Five five-factor personality model") to examine their personality. Six months following surgery, patients were asked to fill a QoV questionnaire where they graded the frequency of 10 common visual symptoms. Primary outcomes were to evaluate the correlation between personality scores and the reported frequency of visual disturbances. RESULTS: The study comprised 20 patients submitted to bilateral cataract surgery, 10 with a non-diffractive X-WAVE lens (AcrySof® IQ Vivity) and 10 with a trifocal lens (AcrySof® IQ PanOptix). Mean age was 60.23 (7.06) years. Six months following surgery, patients with lower scores of conscientiousness and extroversion reported a higher frequency of visual disturbances (blurred vision, P = .015 and P = .009, seeing double images P = .018 and P = .006, and having difficulties focusing, P = .027 and P = .022, respectively). In addition, patients with high neuroticism scores had more difficulty focusing (P = .033). CONCLUSIONS: In this study, personality traits such as low conscientiousness and extroversion and high neuroticism significantly influenced QoV perception 6 months after bilateral multifocal lens implantation. Patients' personality questionnaires could be a useful preoperative assessment test to a mIOL.

Photodynamic therapy for chronic central serous chorioretinopathy: a 4-year follow-up study.

PURPOSE: To evaluate the efficacy and safety of standard photodynamic therapy with verteporfin at 48 months in patients with chronic central serous chorioretinopathy. METHODS: A retrospective, multicenter, interventional case series analysis in patients with chronic central serous chorioretinopathy, treated with standard photodynamic therapy, and with ≥4 years of follow-up. Evaluations were performed every 3 months in the first year, every 6 months in the second year, and thereafter annually. Optical coherence tomography was performed in all visits. Fluorescein angiography and indocyanine green angiography were performed at baseline and thereafter as necessary. Retinal thickness on optical coherence tomography was measured manually, evaluating central macular thickness and neural retina thickness. Main outcomes included the evolution of best-corrected visual acuity, the resolution of subretinal fluid, documented with optical coherence tomography, the number of treatments, and the evaluation of neural retina thickness during the 48 months of follow-up. RESULTS: The study included 46 eyes of 42 patients, 38 men (90.4%) and 4 women (9.5%), with mean age of 49.19 ± 9.9 years (range, 32-70 years), and the minimal follow-up period was 48 months (mean, 56.8 ±10.3 months). Subretinal fluid was observed in all the included eyes at baseline, and 10 eyes (21.7%) had intraretinal diffuse or cystoid fluid. Concerning the mean best-corrected visual acuity, a statistically significant improvement (P < 0.01, Student t-test) was registered from 58.8 ± 18.3 letters at baseline to 66.9 ± 18.6 letters at 48th month. A complete resolution of subretinal fluid was achieved in 93.4%, and resolution of intraretinal fluid occurred in all 10 cases at 48 months. Neural retina thickness remained stable during the 48 months of follow-up (163.8 ± 47 µm at baseline and 163.8 ± 46 µm at 48 months). The mean number of treatments was 1.08 ± 0.3. No systemic or ocular side effects were registered. CONCLUSION: Standard photodynamic therapy with verteporfin was effective and safe in chronic central serous chorioretinopathy treatment with a significant improvement in the long term, both anatomic and visual, without inducing additional retinal atrophy or systemic adverse effects.

Customized corneal crosslinking with excimer laser-assisted epithelium removal for progressive keratoconus: 1-year results.

PURPOSE: To evaluate the 1-year visual and tomographic results of customized crosslinking using excimer laser-assisted epithelium removal and topography-guided irradiation in the treatment of progressive keratoconus. SETTING: Coimbra Ophthalmology Unit, Private Practice, Coimbra, Portugal. DESIGN: Prospective nonrandomized clinical trial. METHODS: Eyes with documented progressive keratoconus were enrolled. After de-epithelialization with phototherapeutic keratectomy, customized UV irradiation was performed, designed as 3 concentric circular areas centered on the thinnest point (Mosaic System). Energy exposure was 5.4 J/cm 2 in the outer circle and then increased centripetally to 7.2 J/cm 2 and 10 J/cm 2 . Corrected distance visual acuity (CDVA), refractive outcomes, and Scheimpflug tomographies (Allegro Oculyzer) were assessed at baseline, and 6 months, and 12 months postoperatively. RESULTS: 37 eyes of 32 patients were enrolled in this prospective study. The mean diameter for treated areas was 6.17 ± 0.80 mm, 4.45 ± 0.47 mm, and 2.58 ± 0.14 mm for the outer, medium, and inner circle, respectively. At the 1-year follow-up, the mean CDVA improved significantly from 0.38 ± 0.19 to 0.20 ± 0.16 logMAR ( P < .01), with 34 (91.89%) of the 37 eyes retaining or improving CDVA. The mean preoperative minimum pachymetry decreased from 449.26 ± 41.62 to 443.26 ± 41.06 µm ( P = .02). The maximum keratometry decreased significantly from 58.50 ± 7.84 to 57.05 ± 7.27 diopters ( P < .01). After 1 year, 34 eyes (91.89%) showed no signs of progression. CONCLUSIONS: 1 year postoperatively, patients showed a significant improvement in visual acuity while achieving stabilization of disease progression.

Comparison of outcomes between cross-linking plus topoguided excimer laser ablation and intrastromal corneal ring segments for keratoconus.

OBJECTIVE: To compare cross-linking (CXL) plus topography-guided photorefractive keratectomy (t-PRK) and intrastromal corneal ring segments (ICRS) in keratoconus patients, at 12 months of follow-up. METHODS: This was a longitudinal, retrospective multi-center study. We included a referred sample of 154 eyes from 149 patients with grade I-III Amsler-Krümeich keratoconus with insufficient corrected-distance visual acuity (CDVA). In group 1 (CXL plus t-PRK, 87 eyes), another possible indication for surgery was evidence of progression. Group 2 (ICRS, 67 eyes) included only eyes with paracentral keratoconus (thinnest point at the inferotemporal quadrant) with coincident axes, and evidence of stabilization was required. A subgroup analysis was performed regarding the disease topographic phenotype. At 12 months postoperatively, visual, refractive, and topographic outcomes were evaluated. RESULTS: Comparison of the outcomes between CXL plus t-PRK (group 1) and ICRS (group 2) showed similar improvements in CDVA (in group 1, CDVA improved 0.18 logMAR, and in group 2 0.12 logMAR, P = .18) and K2 (-2,45 [6.46] D in group 1 and -2.13 [1.67] D in group 2, P = .34) The improvement in cylinder power was greater in group 2 (-2.37 [2.07] D in group 2 versus -1.18 [2.63] D in group 1, P = .003); group 1 had a higher decrease in Kmax (- 3.26 [3.64] versus-1.74 [2.67], P = .001). CONCLUSIONS: Both CXL plus t-PRK and ICRS were equally effective in improving CDVA and topographic parameters in a similar group of keratoconus patients at 12 months.

Risk of Second Tumors in Retinoblastoma Survivors after Ionizing Radiation: A Review.

Retinoblastoma (RB) is the most common ocular neoplasm in children, whose development depends on two mutational events that occur in both alleles of the retinoblastoma susceptibility gene (RB1). Regarding the nature of these mutational events, RB can be classified as hereditary if the first event is a germline mutation and the second one is a somatic mutation in retina cells or nonhereditary if both mutational events occur in somatic cells. Although the rate of survival of RB is significantly elevated, the incidence of second malignant neoplasms (SMNs) is a concern, since SMNs are the main cause of death in these patients. Effectively, RB patients present a higher risk of SMN incidence compared to other oncology patients. Furthermore, evidence confirms that hereditary RB survivors are at a higher risk for SMNs than nonhereditary RB survivors. Over the decades, some studies have been performed to better understand this subject, evaluating the risk of the development of SMNs in RB patients. Furthermore, this risk seems to increase with the use of ionizing radiation in some therapeutic approaches commonly used in the treatment of RB. This review aims to clarify the effect of ionizing radiation in RB patients and to understand the association between the risk of SMN incidence in patients that underwent radiation therapy, especially in hereditary RB individuals.

Photodynamic therapy in highly myopic eyes with choroidal neovascularization: 5 years of follow-up.

PURPOSE: To evaluate the long-term safety and efficacy of photodynamic therapy in the treatment of choroidal neovascularization associated with pathologic myopia. METHODS: Five-year retrospective study of 43 consecutive eyes of 36 patients with juxtafoveal or subfoveal choroidal neovascularization and pathologic myopia treated with photodynamic therapy. RESULTS: Mean best-corrected visual acuity changed from 20/125 +1 letter (0.78 logarithm of the minimum angle of resolution) at baseline to 20/100 (0.70 logarithm of the minimum angle of resolution) at 5 years (P = 0.122). Final best-corrected visual acuity improved in 53.5% of the eyes, remained stable in 11.6%, and decreased in 34.9%. A visual acuity gain of ≥3 lines occurred in 32.6% of the eyes, and a visual acuity decrease of ≥3 lines was registered in 20.9% of the cases at 5 years. Only patient's age and initial visual acuity showed to have a significant predictive value for the final visual acuity outcome (P = 0.024 and P = 0.002, respectively). CONCLUSION: Photodynamic therapy with verteporfin may increase the chance of stabilizing and improving vision in patients with choroidal neovascularization from pathologic myopia at 5 years. Better results were found in younger patients (<55 years).

Intravitreal ranibizumab for myopic choroidal neovascularization: 12-month results.

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of intravitreal ranibizumab after 12 months in the treatment of choroidal neovascularization secondary to pathologic myopia. METHODS: This was a prospective, multicenter, consecutive, nonrandomized, interventional case series. The study included 34 eyes of 32 patients with choroidal neovascularization secondary to pathologic myopia; 13 eyes had previous photodynamic therapy, and 21 eyes had no previous treatment. The patients were followed for > or = 12 months. Best-corrected visual acuity, optical coherence tomography, and the presence of metamorphopsia were assessed monthly. RESULTS: Mean visual acuity improved 8 letters from baseline to 12-month follow-up, and the difference was statistically significant (P < 0.001): 100% of the eyes lost <3 lines on the Early Treatment Diabetic Retinopathy Study chart, 24% of the eyes improved > or = 3 lines, 44% improved > or = 2 lines, 65% improved > or = 1 line, and 79% improved > or = 0 lines. Central retinal thickness decreased significantly from baseline to the 12-month follow-up (P < 0.01). A mean of 3.6 treatments were performed during the 12-month follow-up, and no systemic or ocular side effects were registered during that time. CONCLUSION: One-year results of intravitreal ranibizumab for myopic choroidal neovascularization are very promising. Additional prospective studies are necessary to better determine long-term efficacy and safety.

Macular OCT-angiography parameters to predict the clinical stage of nonproliferative diabetic retinopathy: an exploratory analysis.

BACKGROUND: To test whether a single or a composite set of macular vascular density parameters, evaluated with optical coherence tomography angiography (OCTA), are able to predict nonproliferative diabetic retinopathy (NPDR) staging according to the gold-standard ETDRS-grading scheme. METHODS: Prospectively defined, cross-sectional study in which macular structural and vascular parameters of diabetic eyes with nonproliferative DR (up to ETDRS Level 53) were evaluated with OCTA (Avanti RTVue-XR 100, Optovue Inc, Fremont, CA). Seven-field photographs of the fundus were taken for DR staging according to the ETDRS-grading scheme. The vessel density in the superficial and deep capillary plexus (SCP and DCP, respectively), as well as in the choriocapillaris (CC), were calculated using automated software. Univariate and multivariate ordered logistic regression models were used in the analysis. P < 0.05 was considered statistically significant. RESULTS: We included 101 eyes from 56 subjects (mean (SD) age 62.64 (11.74) years; 57.4% were male). On univariate analysis, several OCTA parameters were found to be associated with higher ETDRS level (parafoveal SCP density: OR = 0.87 (95% CI 0.76-0.99), p = 0.039; parafoveal DCP density: OR = 0.79 (95% CI 0.72-0.87), p < 0.001; CC density: OR = 0.89 (95% CI 0.80-0.99)), p = 0.036). In the final model, while also adjusting for relevant clinical features, only parafoveal vessel density in the DCP remained as a significant predictor of NPDR ETDRS level (OR = 0.54 (95% CI 0.32-0.92), p = 0.024). CONCLUSION: Our results suggest that parafoveal vessel density in the DCP is the parameter most robustly associated with ETDRS level. OCTA analysis may provide objective imaging biomarkers to monitor NPDR clinical progression.

Human Plasma Metabolomics in Age-Related Macular Degeneration: Meta-Analysis of Two Cohorts.

The pathogenesis of age-related macular degeneration (AMD), a leading cause of blindness worldwide, remains only partially understood. This has led to the current lack of accessible and reliable biofluid biomarkers for diagnosis and prognosis, and absence of treatments for dry AMD. This study aimed to assess the plasma metabolomic profiles of AMD and its severity stages with the ultimate goal of contributing to addressing these needs. We recruited two cohorts: Boston, United States (n = 196) and Coimbra, Portugal (n = 295). Fasting blood samples were analyzed using ultra-high performance liquid chromatography mass spectrometry. For each cohort, we compared plasma metabolites of AMD patients versus controls (logistic regression), and across disease stages (permutation-based cumulative logistic regression considering both eyes). Meta-analyses were then used to combine results from the two cohorts. Our results revealed that 28 metabolites differed significantly between AMD patients versus controls (false discovery rate (FDR) q-value: 4.1 × 10-2-1.8 × 10-5), and 67 across disease stages (FDR q-value: 4.5 × 10-2-1.7 × 10-4). Pathway analysis showed significant enrichment of glycerophospholipid, purine, taurine and hypotaurine, and nitrogen metabolism (p-value ≤ 0.04). In conclusion, our findings support that AMD patients present distinct plasma metabolomic profiles, which vary with disease severity. This work contributes to the understanding of AMD pathophysiology, and can be the basis of future biomarkers and precision medicine for this blinding condition.

Low-vision aids improve the visual performance of children with bilateral chorioretinal coloboma.

PURPOSE: To quantify the improvements in visual performance for both distance and near tasks attained by children with bilateral chorioretinal coloboma (CRC) with use of low-vision aids (LVAs). METHODS: This was a hospital-based, cross-sectional, interventional case series of children with bilateral CRC. Demographic data were collected through a structured questionnaire and review of medical records. Distance and near best-corrected visual acuity, contrast sensitivity, and reading speed were evaluated with refractive correction alone and with the use of LVAs (Keplerian telescopes for distance; handheld magnifiers and a tinted lens [400 nm filter] for near). Effects are presented as medians of differences with 95% binomial-exact confidence intervals. RESULTS: Six children were included (median age, 11.5 years; range, 7-17 years), of whom 5 were already using LVAs on a daily basis. The use of a Keplerian telescope achieved a significant median improvement in distance best-corrected visual acuity of 0.75 logMAR (95% CI, 0.20-1.20). Contrast sensitivity was also improved across all tested spatial frequencies. Use of near LVAs resulted in a significant median improvement in near reading acuity of 0.47 logRAD (95% CI, 0.28-0.90). Critical print size and reading speed at N10 were also improved. CONCLUSIONS: LVAs enable meaningful improvements in the visual performance of children with bilateral CRC, allowing noteworthy increases in distance and near visual acuities as well as good reading speeds at small print sizes.

Functional magnetic resonance imaging to assess neuroadaptation to multifocal intraocular lenses.

PURPOSE: To evaluate the use of functional magnetic resonance imaging (MRI) to assess neuroadaptation to multifocal intraocular lenses (IOLs). SETTING: Faculty of Medicine, University of Coimbra, Coimbra, Portugal. DESIGN: Prospective case study. METHODS: Patients with bilateral diffractive IOL implantation after cataract surgery had functional MRI at postoperative intervals of 3 weeks and 6 months. A nonintervention control group was included as proof of concept. Functional stimuli consisted of sinusoidal gratings with threshold contrast and a light source to induce disability glare. Subjective quality of vision and reading performance were assessed and wavefront analyses were performed. RESULTS: The study comprised 30 patients in the study group and 15 in the control group. Glare decreased the functional MRI signal measured for sinusoidal gratings initially (3 weeks) but not at 6 months (P = .04), which was confirmed by contrast detection under glare improvement (P = .002). Patients showed increased activity of cortical areas involved in visual attention, procedural learning, effortful cognitive control, and goal-oriented behavior in the early postoperative period, which normalized at 6 months. There were no differences in aberrations, Strehl ratio, or modulation transfer function despite significant decreases in questionnaire symptom scores and visual acuity and reading performance improvements. The control group remained unchanged. CONCLUSIONS: Neuroadaptation to multifocal IOLs took place initially through recruitment of visual attentional and procedural learning networks. Thereafter, a form of long-term adaptation/functional plasticity occurred, leading to brain activity regularization toward a non-effort pattern. These findings, which reinforce the crucial role of higher-level brain regions in the perceptual construction of vision, were consistent with functional and questionnaire outcomes and were unrelated to optical properties.

Human plasma metabolomics in age-related macular degeneration (AMD) using nuclear magnetic resonance spectroscopy.

PURPOSE: To differentiate the plasma metabolomic profile of patients with age related macular degeneration (AMD) from that of controls, by Nuclear Magnetic Resonance (NMR) spectroscopy. METHODS: Two cohorts (total of 396 subjects) representative of central Portugal and Boston, USA phenotypes were studied. For each cohort, subjects were grouped according to AMD stage (early, intermediate and late). Multivariate analysis of plasma NMR spectra was performed, followed by signal integration and univariate analysis. RESULTS: Small changes were detected in the levels of some amino acids, organic acids, dimethyl sulfone and specific lipid moieties, thus providing some biochemical information on the disease. The possible confounding effects of gender, smoking history and age were assessed in each cohort and found to be minimal when compared to that of the disease. A similar observation was noted in relation to age-related comorbidities. Furthermore, partially distinct putative AMD metabolite fingerprints were noted for the two cohorts studied, reflecting the importance of nutritional and other lifestyle habits in determining AMD metabolic response and potential biomarker fingerprints. Notably, some of the metabolite changes detected were noted as potentially differentiating controls from patients diagnosed with early AMD. CONCLUSION: For the first time, this study showed metabolite changes in the plasma of patients with AMD as compared to controls, using NMR. Geographical origins were seen to affect AMD patients´ metabolic profile and some metabolites were found to be valuable in potentially differentiating controls from early stage AMD patients. Metabolomics has the potential of identifying biomarkers for AMD, and further work in this area is warranted.

Automated Brightness and Contrast Adjustment of Color Fundus Photographs for the Grading of Age-Related Macular Degeneration.

PURPOSE: The purpose of this study was to develop an algorithm to automatically standardize the brightness, contrast, and color balance of digital color fundus photographs used to grade AMD and to validate this algorithm by determining the effects of the standardization on image quality and disease grading. METHODS: Seven-field color photographs of patients (>50 years) with any stage of AMD and a control group were acquired at two study sites, with either the Topcon TRC-50DX or Zeiss FF-450 Plus cameras. Field 2 photographs were analyzed. Pixel brightness values in the red, green, and blue (RGB) color channels were adjusted in custom-built software to make the mean brightness and contrast of the images equal to optimal values determined by the Age-Related Eye Disease Study (AREDS) 2 group. RESULTS: Color photographs of 370 eyes were analyzed. We found a wide range of brightness and contrast values in the images at baseline, even for those taken with the same camera. After processing, image brightness variability (brightest image-dimmest image in a color channel) was reduced 69-fold, 62-fold, and 96-fold for the RGB channels. Contrast variability was reduced 6-fold, 8-fold, and 13-fold, respectively, after adjustment. Of the 23% images considered nongradable before adjustment, only 5.7% remained nongradable. CONCLUSIONS: This automated software enables rapid and accurate standardization of color photographs for AMD grading. TRANSLATIONAL RELEVANCE: This work offers the potential to be the future of assessing and grading AMD from photos for clinical research and teleimaging.

Irregular Astigmatism After Corneal Transplantation--Efficacy and Safety of Topography-Guided Treatment.

PURPOSE: To analyze the efficacy and safety of topography-guided photorefractive keratectomy (TG-PRK) to treat irregular astigmatism after corneal transplantation. METHODS: This was a retrospective observational case series. Eyes with irregular astigmatism after penetrating keratoplasty treated with TG-PRK (Allegretto Wave Eye-Q) with the topography-guided customized ablation treatment protocol were included. All treatments had been planned to correct the topographic irregularities, as well as to reduce the refractive error after neutralizing the induced refractive change. Clinical records, treatment plan, and the examinations performed were reviewed and the following data were collected: corrected and uncorrected distance visual acuities; manifest refraction; topographic parameters, and corneal endothelial cell count. RESULTS: We included 31 eyes [30 patients; mean age 45.0 ± 13.4 (SD) years]. At the last postoperative follow-up (mean 9.2 ± 8.2 months), we observed a significant improvement in corrected (P = 0.001) and uncorrected distance visual acuities (P < 0.001). There was a gain of ≥1 uncorrected distance visual acuity line in 96.8% (n = 30) of the eyes. Similarly, the refractive parameters also improved (cylinder P < 0.001; spherical equivalent P = 0.002). At the last visit, 54.8% (n = 17) of the patients presented a spherical equivalent of ±1 D. The 3-mm topographic irregularity also decreased significantly (P < 0.001). There was no significant variation of the corneal endothelial cell count. CONCLUSIONS: This is the largest case series of TG-PRK to treat irregular astigmatism in postcorneal transplantation eyes. Our results confirm that TG-PRK is an efficient treatment, associated with significant improvements of both visual acuity and refractive parameters.