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Guilherme Castela,1,2 Joana Providência,1,2 Madalena Monteiro,1 Sónia Silva,3 Manuel Brito,3 Joaquim Neto Murta,1,2 Zélia Correa,4 Miguel Castelo Branco2 1Department of Ophthalmology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; 2Faculty of Medicine, University of Coimbra, Coimbra, Portugal; 3Department of Pediatric Oncology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; 4Bascon Palmer Eye Institute, Miami, FL, USACorrespondence: Guilherme CastelaDepartment of Ophthalmology, Centro Hospitalar e Universitário de Coimbra, Avenida Dias da Silva 164, Coimbra, 3000, PortugalEmail gcastela@hotmail.comObjective: The aim of our study was to characterize the evacuated African patients diagnosed with retinoblastoma and referred to the Portuguese national referral center (Centro Hospital e Universitário de Coimbra, University of Coimbra), identifying inequalities in the stage of diagnosis and prognostic results.Design: Retrospective observational study of evacuated African patients diagnosed with retinoblastoma and referred to the Portuguese National Referral Center (Centro Hospital e Universitário de Coimbra, University of Coimbra).Results: The study included 15 patients between October 2015 and October 2020 from Angola, Cape Verde, Guinea-Bissau and São Tomé and Príncipe. Seven (46.7%) children presented bilateral retinoblastoma. The median age at the time of diagnosis was 20.9 (interquartile range, 16– 41) months. The presenting symptoms were leukocoria (86.7%), strabism (53.3%) and buphthalmus (40%). In terms of tumor staging, five (33.3%) children presented with extraocular retinoblastoma and 10 (66.7%) children presented with intraocular retinoblastoma. At presentation, no pineal involvement was diagnosed but two (13.3%) children presented with central nervous system involvement at the time of the first observation. Children were treated with enucleation, exenteration, systemic chemotherapy, intra-arterial chemotherapy and/or supportive palliative care. During the follow-up period (mean 27.2 ± 18.2 months), the overall survival was 73.3%.Conclusion: A small proportion of African children are being referred to our center, when considering the expected incidence of retinoblastoma in these countries, and referred children arrive at advanced stages of the disease, compromising treatment outcomes. Considering retinoblastoma is now a curable disease, national and international interventions are required to attempt a better management of children born in low-income countries.Keywords: retinoblastoma, low income countries, treatment of advanced disease

The VEMoS-AXL system is a new optical biometer based on spectral domain optical coherence tomography (SD-OCT) that has been tested in terms of intrasession repeatability and compared with a swept-source optical coherence tomography biometer (SS-OCT), which is recognized as the gold standard for the performance of an agreement analysis. A biometric analysis was performed three consecutive times in 120 healthy eyes of 120 patients aged between 18 and 40 years with the SD-OCT system, and afterwards, a single measurement was obtained with the SS-OCT system. Within-subject standard deviations were 0.004 mm, 4.394 µm, and 0.017 mm for axial length (AL), central corneal thickness (CCT), and anterior chamber depth (ACD) measures obtained with the SD-OCT biometer, respectively. The agreement between devices was good for AL (limits of agreement, LoA: -0.04 to 0.03 mm) and CCT (LoA: -4.36 to 14.38 µm), whereas differences between devices were clinically relevant for ACD (LoA: 0.03 to 0.21 mm). In conclusion, the VEMoS-AXL system provides consistent measures of anatomical parameters, being most of them interchangeable with those provided by the SS-OCT-based gold standard.

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., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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.

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., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

The purpose of this study is to characterize demographically and genetically the Portuguese population with retinoblastoma; to report the clinical stage at presentation and its impact on survival and ocular preservation rate and, finally, to assess the incidence of retinoblastoma in Portugal. Retrospective observational study including children consecutively diagnosed with retinoblastoma at the Portuguese National Referral Center of Intraocular Tumors, between October 2015 and October 2020. Twenty-eight children were diagnosed with retinoblastoma at our center, 15 hereditary from which 12 presented with bilateral retinoblastoma and 3 were unilateral. The overall mean age at diagnosis was 13.6 ± 11.1 months with hereditary retinoblastomas diagnosed slightly earlier at 9.6 ± 6.3 months. A familial history of retinoblastoma was found in only 4 (14.3%) of the cases. A pathogenic mutation in the RB1 gene was found in 13 (46.4%) of the children. The most frequent sign at referral was leukocoria in 71.4% of patients. Considering the ICRB classification of the tumors, 84.6% of non-hereditable hereditary retinoblastomas were referred to our center in advanced stages. In the group of hereditable retinoblastomas 86.7% presented with one of the eyes with advanced intraocular retinoblastoma. Fourteen children had one eye enucleated due to retinoblastoma. No deaths were registered during the study period. Considering the incidence analysis, we registered a year-of-birth controlled incidence analysis of 4.04 per 100.000 living births (IC 95% 1.59-6.49). This is the first characterization of the Portuguese Population diagnosed with Retinoblastoma in the National Reference Center., (© 2022. The Author(s).)

We and others have shown that patients with different severity stages of age-related macular degeneration (AMD) have distinct plasma metabolomic profiles compared to controls. Urine is a biofluid that can be obtained non-invasively and, in other fields, urine metabolomics has been proposed as a feasible alternative to plasma biomarkers. However, no studies have applied urinary mass spectrometry (MS) metabolomics to AMD. This study aimed to assess urinary metabolomic profiles of patients with different stages of AMD and a control group. We included two prospectively designed, multicenter, cross-sectional study cohorts: Boston, US ( n = 185) and Coimbra, Portugal ( n = 299). We collected fasting urine samples, which were used for metabolomic profiling (Ultrahigh Performance Liquid chromatography-Mass Spectrometry). Multivariable logistic and ordinal logistic regression models were used for analysis, accounting for gender, age, body mass index and use of AREDS supplementation. Results from both cohorts were then meta-analyzed. No significant differences in urine metabolites were seen when comparing patients with AMD and controls. When disease severity was considered as an outcome, six urinary metabolites differed significantly ( p < 0.01). In particular, two of the metabolites identified have been previously shown by our group to also differ in the plasma of patients of AMD compared to controls and across severity stages. While there are fewer urinary metabolites associated with AMD than plasma metabolites, this study identified some differences across stages of disease that support previous work performed with plasma, thus highlighting the potential of these metabolites as future biomarkers for AMD.

Purpose: To compare phenotypic and genetic variations in polypoidal choroidal vasculopathy (PCV) between Caucasian and Asian patients., Methods: We analysed phenotypic and genotypic data from two sites, Association for Innovation and Biomedical Research on Light and Image, Portugal and Singapore National Eye Centre, Singapore. Baseline fundus photography, spectral domain-optical coherence tomography, indocyanine green and fluorescein angiography scans were analysed by respective reading centres using a standardised grading protocol. Single nucleotide polymorphisms across 8 PCV loci were compared between cases and controls selected from each population., Results: One hundred and forty treatment-naïve PCV participants (35 Portuguese and 105 Singaporean) were included. The Portuguese cohort were older (72.33±8.44 vs 68.71±9.40 years, p=0.043) and were comprised of a lower proportion of males (43% vs 71%, p=0.005) compared with the Singaporean cohort. Differences in imaging features include higher prevalence of soft drusen (66% vs 30%, p=0.004), lower prevalence of subretinal haemorrhage (14% vs 67%, p<0.001), smaller polypoidal lesion (PL) area (0.09±0.09 vs 0.76±0.93 mm 2 , p<0.001), lower ratio of PL to branching vascular network area (3% vs 38%, p<0.001) and lower central retinal thickness (346.48±93.74 vs 493.16±212.92 µm, p<0.001) in the Portuguese cohort. CETP rs3764261 (OR 2.467; 95% CI 1.282 to 4.745, p=0.006) in the Portuguese population was significantly associated with PCV and CFH rs800292 (OR 1.719; 95% CI 1.139 to 2.596, p=0.010) in the Singaporean population, respectively., Conclusion: Among Asian and Caucasian patients with PCV, there are significant differences in the expression of phenotype. We also identified different polymorphisms associated with PCV in the two populations., Competing Interests: Competing interests: RS reported receiving personal fees as member of the advisory board for Allergan, Alimera Sciences, Bayer, Novartis, Roche, Novo Nordisk and Thea Pharmaceuticals; JNM is a member of the scientific advisory board of Alcon; JF reported being a member of advisory boards for Alimera, Allergan, Bayer, Boehringer and Novartis; SV-P reported receiving personal fees as a consultant for Alimera Sciences, Bayer and Novartis. FC reported receiving personal fees as a consultant for Bayer, Allergan, Novartis, Brill-Alimera, Roche, Alcon and Dorc. AB reported receiving from Bayer consultation fees (advisory board), speaker fees, travel fees (for meetings) and reported receiving from Allergan consultation fees (advisory board), speaker fees, and travel fees (for meetings). The other authors declare that they have no conflict of interest., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To comparatively evaluate the accuracy of newer intraocular lens (IOL) calculation formulas and common third-generation formulas after Wang-Koch adjustment in the prediction of postoperative refraction in highly myopic eyes., Methods: This was a retrospective study including eyes with high myopia that had uncomplicated cataract surgery with implantation of an AcrySof MA60MA IOL (power range: -5.00 to +5.00 diopters [D]) (Alcon Laboratories, Inc). All patients underwent optical biometry (Carl Zeiss IOLMaster 500 and IOLMaster 700, and Allegro Biograph) and the postoperative spherical equivalent for the implanted IOL was estimated using SRK/T, Holladay 1 (both Wang-Koch adjusted), Haigis, Barrett Universal II, Kane, Ladas, and Hill-RBF v2.0 formulas. Outcomes included the median absolute prediction error (MedAE) and the proportion of eyes within ±0.25, ±0.50, and ±1.00 D of the preoperative prediction., Results: Eighty-two eyes with a mean axial length of 30.89 ± 1.85 mm were included. The MedAE in ascending order was Hill-RBF v2.0 0.31 D, Kane 0.33 D, Barrett 0.36 D, Holladay I wk 0.37 D, SRK/T wk 0.37 D, Holladay I wk 0.43 D, Haigis ULIB 0.54 D, and Ladas 0.61 D. The formula with the lowest MedAE (Hill-RBF v2.0) yielded a prediction error within ±0.25, ±0.50, and ±1.00 D in 43.1%, 70.6%, and 94.1% of cases, respectively., Conclusions: Recent formulas such as Barrett Universal II, Kane, and Hill-RBF v2.0 and Wang-Koch adjusted formulas perform well in this subset of patients with high myopia. The Hill-RBF v2.0 formula had the lowest MedAE and highest proportion of eyes within ±0.25, ±0.50, and ±1.00 D of the predicted target. [ J Refract Surg . 2021;37(3):207-211.] .

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., (© 2021 S. Karger AG, Basel.)

Background: The development of multicenter patient registries promotes the generation of scientific knowledge by using real-world data. A country-wide, web-based registry for inherited retinal dystrophies (IRDs) empowers patients and community organizations, while supporting formal partnerships research. We aim to describe the design, development and deployment of a country-wide, with investigators and stakeholders in the global aim to develop high-value, high-utility web-based, user-friendly and interoperable registry for IRDs-the IRD-PT., Results: The IRD-PT is a clinical/genetic research registry included in the retina.pt platform ( https://www.retina.com.pt ), which was developed by the Portuguese Retina Study Group. The retina.pt platform collects data on individuals diagnosed with retinal diseases, from several sites across Portugal, with over 1800 participants and over 30,000 consultations to date. The IRD-PT module interacts with the retina.pt core system which provides a range of basic functions for patient data management, while the IRD-PT module allows data capture for the specific purpose of IRDs. All IRDs are coded accordingly to the International Statistical Classification of Diseases and Related Health Problems (ICD) 9, ICD 10, ICD 11, and Orphanet Rare Disease Ontology (ORPHA codes) to make the IRD-PT interoperable with other IRD registries across the world. Furthermore, the genes are coded according to the Ontology of Genes and Genomes and Online Mendelian Inheritance in Man, whereas signs and symptoms are coded according to the Human Phenotype Ontology. The IRD-PT module pre-launched at Centro Hospitalar e Universitário de Coimbra, the largest reference center for IRDs in Portugal. As of April 1st 2020, finalized data from 537 participants were available for this preliminary analysis., Conclusions: In the specific field of rare diseases, the use of registries increases research accessibility for individuals, while providing clinicians/investigators with a coherent data ecosystem necessary to boost research. Appropriate design and implementation of patient registries enables rapid decision making and ongoing data mining, ultimately leading to improved patient outcomes. We have described here the principles behind the design, development and deployment of a web-based, user-friendly and interoperable software tool aimed to generate important knowledge and collecting high-quality data on the epidemiology, genomic landscape and natural history of IRDs in Portugal.

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: β = -2.95, P < 0.001; mild NPDR: β = -1.76, P = 0.017; and moderate NPDR: β = -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.

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.

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.

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.

Biofluid biomarkers of age-related macular degeneration (AMD) are still lacking, and their identification is challenging. Metabolomics is well-suited to address this need, and urine is a valuable accessible biofluid. This study aimed to characterize the urinary metabolomic signatures of patients with different stages of AMD and a control group (>50 years). It was a prospective, cross-sectional study, where subjects from two cohorts were included: 305 from Coimbra, Portugal (AMD patients n = 252; controls n = 53) and 194 from Boston, United States (AMD patients n = 147; controls n = 47). For all participants, we obtained color fundus photographs (for AMD staging) and fasting urine samples, which were analyzed using 1 H nuclear magnetic resonance (NMR) spectroscopy. Our results revealed that in both cohorts, urinary metabolomic profiles differed mostly between controls and late AMD patients, but important differences were also found between controls and subjects with early AMD. Analysis of the metabolites responsible for these separations revealed that, even though distinct features were observed for each cohort, AMD was in general associated with depletion of excreted citrate and selected amino acids at some stage of the disease, suggesting enhanced energy requirements. In conclusion, NMR metabolomics enabled the identification of urinary signals of AMD and its severity stages, which might represent potential metabolomic biomarkers of the disease.

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., (Copyright © 2018 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the efficacy and tolerance of a new matrix-regenerating agent (RGTA), Cacicol ® , a polymer that mimics heparan sulfates bound to extracellular matrix proteins, avoiding its proteolysis, to treat neurotrophic keratopathy (NK)., Methods: Uncontrolled prospective clinical study performed between January 2014 and May 2016. Twenty-five patients (25 eyes) with corneal neurotrophic ulcers, nonresponsive to at least 2 weeks of conservative therapy, were treated with Cacicol, instilled once/twice a week. During follow-up, slit-lamp examination, anterior segment photography, fluorescein-dye testing, and best-corrected visual acuity were analyzed. Ulcer evolution was evaluated using image analysis software (ImageJ ® ) and healing defined as decrease of the corneal ulcer area. An independent observer measured ulcer area., Results: All patients had complete corneal healing within an average of 4.13 ± 2.32 weeks. Mean ulcer area decreased significantly (P = 0.001) from 16.51% ± 18.56% (1st day) to 8.68% ± 11.25% at the 7th day and to 4.73% ± 10.75% at the 14th day. Compared with day 1, mean ulcer area decreased 60.24% after 7 days (P = 0.001), 54.92% after 14 days (P = 0.059), and 83.00% after 21 days (P = 0.003). Two cases of recurrence (8.0%) were registered. No systemic or local side effects were noticed., Conclusions: The new regenerating agent, Cacicol, represents an effective and safe therapy to treat NK.

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., (Copyright © 2017 ASCRS and ESCRS. All rights reserved.)

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., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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.

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.

Purpose: To compare endothelial cell (EC) variation after anterior chamber phakic intraocular lens (AC-pIOL) implantation in highly myopic patients with a preoperative anterior chamber depth (ACD) between 2.8 and 3.0 versus ≥3.0 mm., Methods: A total of 280 eyes submitted to primary AC-pIOL implantation were analyzed. Pre- and postoperative values for uncorrected distance visual acuity, corrected distance visual acuity, spherical equivalent, ACD (endothelial surface), and EC count were collected. The eyes were divided into 2 groups: group A - ACD between 2.8 and 3.0 mm; group B - ACD ≥3.0 mm. Mean global EC loss (ECL) and loss for each ACD group, according to pIOL type, were analyzed., Results: Significant improvement of the spherical equivalent (-11.38 ± 4.57 vs. -0.49 ± 0.79; p = 0.000) and a significant decrease in EC density (2,810.95 ± 343.88 vs. 2,584.09 ± 374.88 cells/mm2; p = 0.000) were noted. The mean annual ECL was -2.19 ± 3.97%. Regarding group A (n = 80), a mean annual ECL of -2.06 ± 3.88% was registered, higher for the Acrysof Cachet® subtype, while group B (n = 200) showed -2.25 ± 4.01% ECL, higher for the Verisyse® subtype. There was no significant difference between the groups (p = 0.96)., Conclusions: AC-pIOL implantation significantly improves the spherical equivalent in myopic patients. The mean annual ECL after pIOL implantation was higher in the larger ACD group, but this value was not statistically significant. A 2.8-mm ACD value seems to be a safe cutoff for AC-pIOL implantation., (© 2017 S. Karger AG, Basel.)

Purpose: To report late postoperative opacification of a model of hydrophilic-hydrophobic acrylic intraocular lens (IOL) as well as the clinical consequences and laboratory characteristics., Setting: Department of Ophthalmology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal., Design: Retrospective case series., Methods: Medical records were reviewed of patients with Lentis LS-502-1 IOL opacification reporting visual loss who had IOL explantation between November 2013 and March 2015. Patients were identified in the emergency room or during regular follow-up visits. Explanted IOLs were analyzed at the Ophthalmic Explants Biobank, Vissum, Spain, or at the John A. Moran Eye Center, University of Utah, USA., Results: Twenty opacified IOLs were explanted from 19 patients. The mean interval between cataract surgery and diagnosis of opacification was 29.15 months ± 9.57 (SD) (range 6 to 45 months). Opacification led to a statistically significant reduction in corrected distance visual acuity (mean 0.86 ± 0.76 logMAR; P < .001) and occurred in 5.1% of the hydrophilic-hydrophobic acrylic IOLs implanted at the department. The most frequently associated medical conditions were arterial hypertension, diabetes, and glaucoma. All IOLs but 1 had a similar pattern of opacification, with yellowish diffuse opacification uniformly distributed and calcium deposits on the surface and/or subsurface of the optic and haptics and within the IOL material., Conclusions: Opacification of the hydrophilic-hydrophobic acrylic IOL was found in a significant number of patients and had a significant effect on their vision. The opacification was attributed to primary calcification., Financial Disclosure: None of the authors has a financial or proprietary interest in any material or method mentioned., (Copyright © 2016 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To develop 27 short sentence optotypes for the Portuguese version of the Radner Reading Charts., Methods: Thirty-four Portuguese sentences were constructed following the concept of the Radner Reading Charts to obtain highly comparable sentences in terms of lexical difficulty, syntactical complexity, word length, number of syllables, and position of words. A long text (106 words) at the 5th grade reading level was also tested to assess the validity of the reading speeds obtained with the short sentences. The short sentences and long text were tested in 50 volunteers with similar educational backgrounds (mean age 30.98 years ± 6.99 years, range 19-47 years). Reading speeds were measured with a stop-watch and reported as words per minute (wpm). The reading time for each of the short sentences to be selected for the chart was defined as falling within the range of the mean ± 0.40 × standard deviation (SD)., Results: The overall mean reading speed for each of the short sentences was 235.43 ± 36.39 wpm. The 27 sentences with a mean between 220.8 and 250.0 wpm (overall mean ± 0.40 × SD) were selected for construction of the reading charts. The mean reading speed for the long text was 212.42 ± 26.20 wpm. Correlation between the selected short sentences and long text was high (r =0.86). Reliability analysis yielded an overall Cronbach's alpha coefficient of 0.97., Conclusions: The 27 short Portuguese sentences were highly comparable in terms of syntactical structure, number, position and length of words, lexical difficulty, and reading length. This reading test can overcome the limitations of the current tests for homogeneity and comparability, reducing subjectivity in the evaluation of the functional outcomes of medical and surgical ophthalmologic treatments.

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.

Purpose: To quantitatively evaluate visual function 12 months after bilateral implantation of the Physiol FineVision® trifocal intraocular lens (IOL) and to compare these results with those obtained in the first postoperative month., Methods: In this prospective case series, 20 eyes of 10 consecutive patients were included. Monocular and binocular, uncorrected and corrected visual acuities (distance, near, and intermediate) were measured. Metrovision® was used to test contrast sensitivity under static and dynamic conditions, both in photopic and low-mesopic settings. The same software was used for pupillometry and glare evaluation. Motion, achromatic, and chromatic contrast discrimination were tested using 2 innovative psychophysical tests. A complete ophthalmologic examination was performed preoperatively and at 1, 3, 6, and 12 months postoperatively. Psychophysical tests were performed 1 month after surgery and repeated 12 months postoperatively., Results: Final distance uncorrected visual acuity (VA) was 0.00 ± 0.08 and distance corrected VA was 0.00 ± 0.05 logMAR. Distance corrected near VA was 0.00 ± 0.09 and distance corrected intermediate VA was 0.00 ± 0.06 logMAR. Glare testing, pupillometry, contrast sensitivity, motion, and chromatic and achromatic contrast discrimination did not differ significantly between the first and last visit (p&gt;0.05) or when compared to an age-matched control group (p&gt;0.05)., Conclusions: The Physiol FineVision® trifocal IOL provided satisfactory full range of vision and quality of vision parameters 12 months after surgery. Visual acuity and psychophysical tests did not vary significantly between the first and last visit.

Purpose: This paper aims to review the morphological and functional characteristics of patients affected by familial amyloid polyneuropathy (FAP), with greater focus on type I and its progression after liver transplantation. We also analyse therapeutic options for the ophthalmic manifestations., Methods: The literature from 2002 through 2015 was reviewed, with a total of 45 articles studied, using the key terms related to amyloidosis and its therapeutic approaches. Information was collated, evaluated, critically assessed, and then summarised in its present form. PATHOPHYSIOLOGY AND TREATMENT: FAP results from mutation of the transthyretin gene, with Val30Met being the most frequent substitution. The symptoms are those typical of a sensorimotor autonomic neuropathy and can be halted with liver transplantation. Nowadays there are new medical therapies that delay the progression of the systemic neuropathy. However, there are still no options to avoid ocular disease., Conclusion: The main ocular manifestations in patients with FAP type I are amyloid deposition in the vitreous, dry eye, and secondary glaucoma. Despite liver transplantation, eye synthesis of amyloid persists and is associated with progressive ocular manifestations, which require continued ophthalmologic follow-up. New therapeutic strategies are therefore needed, particularly to target the ocular synthesis of the abnormal protein.

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.

Purpose: To compare visual function after bilateral implantation of multifocal Lentis Mplus LS-312 (Group A) or Acrysof Restor SN6AD1 (Group B) intraocular lenses (IOLs)., Setting: Ophthalmology Unit, Centro Hospitalar e Universitário de Coimbra, and Visual Neuroscience Laboratory, IBILI, Faculty of Medicine, University of Coimbra, Coimbra, Portugal., Design: Comparative case series., Methods: Patients between 49 years and 76 years had bilateral cataract surgery with multifocal IOL implantation. Patients were evaluated preoperatively and 3 months postoperatively for distance, intermediate, and near visual acuities; static photopic and mesopic contrast sensitivity; and visual acuity under a glare source using the Metrovision contrast sensitivity platform. Color vision was evaluated with the Cambridge Colour Test., Results: Group A comprised 56 eyes and Group B, 44 eyes. Visual and refractive results were comparable between the 2 groups. Photopic contrast sensitivity was significantly better in Group B at intermediate (2.2 cycles per degree [cpd] and 3.4 cpd) and high (7.1 cpd and 23.6 cpd) spatial frequencies. Under low mesopic conditions (0.08 candelas/m(2)), differences were significant at 1.1 cpd and 2.2 cpd spatial frequencies. There were no differences in visual acuity under a glare source or in color vision., Conclusions: Both IOLs provided good distance, intermediate, and near visual acuities. Visual acuity under a glare source and color vision were similar in the 2 groups. However, photopic and low mesopic contrast sensitivities were better in Group B, particularly for intermediate spatial frequencies, which are important for night driving., (Copyright © 2013 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Aim: To perform Descemet stripping automated endothelial keratoplasty (DSAEK) using a novel technique to obtain very thin (<100 µm) posterior corneal disks., Methods: Twenty five DSAEK grafts were prepared with two sequential cuts: the first cut, of variable thickness, was made with a femtosecond laser and the second with a 300 µm microkeratome head. Spectacle corrected visual acuity, endothelial cell density evaluation with specular microscopy and anterior segment optical coherence tomography to measure central and peripheral graft thickness was performed preoperatively and postoperatively at 1, 3 and 6 months., Results: There were no irregular cuts or perforations during tissue preparation. Central graft thickness was 79.6 µm (SD ± 14.5; range 54-98) and 69.3 µm (SD ± 14.2; range 49-96) at 3 and 6 months. Corrected distance visual acuity improved from 0.91 logMAR preoperatively to 0.11 logMAR at 6 months. Donor endothelial cells averaged 2675 cells/mm(2) preoperatively and 1729 cells/mm(2) at 6 months. There were no graft detachments., Conclusions: This new technique consistently yielded very thin grafts (<100 µm), excellent visual acuity results and good endothelial cell counts. No donor tissue was wasted.

Purpose: To evaluate the use of a femtosecond laser combined with a microkeratome in the preparation of posterior corneal disks for Descemet stripping automated endothelial keratoplasty (DSAEK)., Methods: This experimental study involved ultrathin DSAEK tissue preparation of 22 donor corneas unsuitable for transplantation. The first cut was performed with an Intralase® FS60 laser and the second cut with a Moria CBm 300-µm microkeratome. The thickness of the first cut was modified for each cornea to obtain a final graft thickness of less than 110 µm. Precut and postcut central pachymetry were performed with an ultrasonic pachymeter. Central endothelial cell density (ECD) was calculated before and 24 hours after tissue preparation., Results: Final graft thickness was 105.0 ± 26.1 (SD) µm (range 65-117). The mean microkeratome head cut thickness was 324.5 ± 10.9 µm (range 310-345). Precut and postcut ECDs averaged 2250 ± 222 and 2093 ± 286 cells/mm2, respectively, representing 6.9% of cell loss. No corneas were perforated., Conclusion: Femtosecond FS60 lasers and Moria CBm 300-µm microkeratomes can be used sequentially to prepare consistently thin DSAEK grafts with no irregular cuts or cornea perforations.

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.

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).

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.

Purpose: Diabetes is accompanied by an increased autofluorescence of the cornea, probably because of accumulation of advanced glycation end products (AGEs). The pathogenic mechanism is still unknown. This study aimed to quantify differences in corneal cell densities between diabetic patients and healthy controls., Methods: The left cornea of 15 patients with non-insulin-dependent diabetes mellitus (NIDDM) with level of retinopathy 20 according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) and of 15 healthy controls were examined by noninvasive in vivo confocal microscopy in an observational prospective study. The cell densities in 6 corneal layers were determined along the optical axis of the cornea by using stereologic methods., Results: The average cell density per unit area in the superficial and basal epithelium and the endothelial layer was 725 +/- 171, 5950 +/- 653, and 2690 +/- 302 cells/mm in controls and 815 +/- 260, 5060 +/- 301, and 2660 +/- 364 cells/mm in diabetic patients. The cell density per unit volume in the anterior, mid-, and posterior stroma was 26,300 +/- 4090, 19,390 +/- 3120, and 25,700 +/- 3260 cells/mm in controls and 27,560 +/- 3880, 21,930 +/- 2110, and 25,790 +/- 3090 cells/mm in patients with diabetes. In both groups, the density in the midstroma was significantly lower than in both the anterior stroma and the posterior stroma (P < 0.02). The cell density in the basal layer of diabetic patients was significantly lower than in healthy controls (-15.0%, P < 0.0004). In the other layers, no significant differences between both groups (P > 0.07) were observed., Conclusions: The lower basal cell density found in patients with diabetes may result from a combination of different mechanisms including decreased innervation at the subbasal nerve plexus, basement membrane alterations, and higher turnover rate in basal epithelial cells. The lower cell density in the midstroma of diabetic patients and healthy controls may be attributed in part to differences in oxygen concentration in the stromal layers (depths). Changes in cellular density did not seem to be responsible for the increased autofluorescence in diabetes.

Microperfusion techniques were used to characterize in vitro the fluorescein transport and fluid movement across isolated diabetic rabbit retinal vessels. Unbranched segments of arterioles of alloxan-induced diabetic rabbits were isolated and cannulated on a microperfusion apparatus. Movement of 3H-inulin, the reference tracer, and 14C-fluorescein, the test tracer, across the vascular walls was studied using microperfusion techniques adapted by us to study vascular permeability. The diabetic retinal vessels showed a fluid flux from bath to lumen of 3.6 +/- 0.6 nl min-1 mm-1 with perfusion rates of 7.1 +/- 0.3 nl min-1. This value was 43% (P < or = 0.05) lower when compared with normal values obtained in previous work. Bath to lumen fluorescein fluxes were 2.1 +/- 0.5 and 7.6 +/- 1.6 x 10(-12) mol min-1 mm-1, for fluorescein concentrations of 0.87 x 10(-4) and 1.5 x 10(-4) M, respectively. These values are 23% (P < or = 0.05) and 38.7% (P < or = 0.05), respectively, lower when compared to values obtained from normal retinal vessels. Probenecid, a competitive inhibitor of organic anion transport, added to the bath, had no effect. Increasing bath concentrations of fluorescein caused increasing fluid flux from bath to lumen, and again, probenecid added to the bath has no effect. These results show a significant decrease of fluorescein transport and of net fluid flux across diabetic retinal vessel walls from outside into the lumen, suggesting that in experimental alloxan-induced diabetes there is an early, probably functional, involvement of the retinal vessels in the initial alteration of the blood-retinal barrier (BRB).

Photorefractive keratectomy (PRK) was performed on 98 consecutive normal myopic eyes with the Summit OmniMed laser System. The minimum follow-up was 3 months and 31 were followed for 6 months. Preoperative myopia ranged from -1.25 to -12.00 D. The myopic eyes were divided into 4 groups according to the amount of myopia: group 1 (-1.25 to -3.00 D), 17 eyes; group 2 (-3.12 to -6.00 D), 42 eyes; group 3 (-6.12 to -9.00 D), 29 eyes and group 4 (> 9.00 D), 10 eyes. In group 1 mean uncorrected visual acuity was 0.87 at 3 months, 1.0 at 6 months and all of the eyes were within 0.50 D of the attempted correction. In group 2 mean uncorrected visual acuity was 0.76 at 3 months, 0.87 at 6 months and 92.3% of the eyes were within 0.50 D of the attempted correction. In group 3 mean uncorrected visual acuity was 0.65 and 0.66 at 3 and 6 months respectively and 77.8% of eyes were within 0.50 D of the attempted refractive correction. In group 4, mean uncorrected visual acuity was 0.46 and 0.7 at 3 and 6 months, respectively, and 100% were within 0.50 D of the attempted correction. Two eyes lost 2 lines and 4 eyes gained 2 or more lines of their preoperative best spectacle corrected visual acuity. Three eyes exhibited steroid induced rise in intraocular pressure that was controlled with topical timolol. No serious complications occurred. Despite the short follow-up, photorefractive keratectomy with the 193 nm excimer laser appears to be an effective and safe treatment for the correction of myopia.

The Authors retrospectively evaluated the evolution of corneal astigmatism 6, 12 and 24 months after penetrating keratoplasty in 75 eyes by comparing 2 suture techniques: running suture (RS) in 14 cases vs interrupted suture (IS) in 61 cases. The mean keratometric astigmatism in patients with RS was 7.75 +/- 3.10 D at 6 months, 5.89 +/- 2.50 D at 12 months and 3.90 +/- 1.70 D at 24 months. In patients with IS these values were 4.82 +/- 4.00 D at 6 months, 2.81 +/- 1.60 D at 12 months and 2.77 +/- 1.34 D at 24 months. A significant lower astigmatism (P < 0.05) was noted after using IS at 6 and 12 months. At 24 months, however, this difference was no longer statistically significant (P > 0.3). The IS suture allowed a better control of the post-surgical astigmatism, and a more rapid recovery of the visual acuity.

We developed an experimental model to study the permeability of individual retinal vessels in vitro using microperfusion techniques adapted from kidney tubule studies. The retinal vessels were isolated by freehand dissection and mounted on a microperfusion apparatus. When inulin was perfused luminally, it was diluted to 80.2 +/- 2.3% of its initial concentration. However, no radioactive leak into the bath side was observed, suggesting that the dilution was due to fluid flux from bath to lumen. The dilution of fluorescein (81.9 +/- 3.8%) was in the same range as that of inulin, the reference marker. The extremely low lumen-to-bath fluorescein flux, 0.5 +/- 0.9 X 10(-12) mol/min/mm, increased by 68% when probenecid was added to the perfusate and by 210% when probenecid was placed in the bath. The effect was concentration-dependent. When placed in the bath, fluorescein moved rapidly across the retinal vessel walls, accumulating in the lumen to concentrations 40 times higher than in the bath. This movement from bath to lumen, which was much higher (13.6 +/- 0.3 X 10(-12) mol/min/mm) than the lumen-to-bath fluorescein flux for the same fluorescein concentration, decreased by adding probenecid to the bath. The kinetics of this unidirectional movement of fluorescein were consistent with a saturable active transport process. The fluid flux from bath to lumen across the retinal vessels, which was 6.3 +/- 1.0 nl/min/mm for perfusion rates of 6.6 +/- 0.2 nl/min, was temperature-dependent and was coupled to the fluorescein transport. Fluorescein stimulated the fluid flux by 17% when added to the perfusate and by 60% when added to the bath, and this effect could be reversed by probenecid. Our results showed an active transport of fluorescein in the rabbit retinal vessels coupled with net fluid flux from outside the vessels into the lumen.