Search

Phenotypic heterogeneity with variable severity has been reported in female carriers of retinitis pigmentosa GTPase regulator (RPGR) mutations, including a male-type phenotype. A phenomenon not fully understood is peripapillary retinal nerve fiber layer (pRNFL) thickening in male patients with RPGR-associated X-linked retinitis pigmentosa, especially in the temporal sector. We aim to describe the genetic spectrum, retinal phenotypes, and pRNFL thickness in a cohort of Caucasian RPGR-mutation heterozygotes.A cross-sectional study was conducted at an inherited retinal degeneration (IRD) reference center in Portugal. Female patients heterozygous for clinically significant RPGR variants were identified using the IRD-PT registry. A complete ophthalmologic examination was performed, complemented by macular and peripapillary spectral domain optical coherence tomography (SD-OCT), ultra-widefield color fundus photography (UW-CFP), and ultra-widefield fundus autofluorescence (UW-FAF). The retinal phenotypes were graded according to previously described classifications. The pRNFL thickness across the superior, inferior, nasal, and temporal quadrants was compared to the Spectralis® RNFL age-adjusted reference database.Forty-eight eyes from 24 females (10 families) were included in the study. Genetic analysis yielded 8 distinct clinically significant frameshift variants in RPGR gene, 3 of which herein reported for the first time. No association was found between mutation location and best-corrected visual acuity (BCVA) or retinal phenotype. Age was associated with worse BCVA and more advanced phenotypes on SD-OCT, UW-CFP, and UW-FAF. Seven women (29.17%) presented a male-type phenotype on UW-FAF in at least one eye. An association was found between UW-FAF and pRNFL thickness in the temporal sector (p = 0.003), with the most advanced fundus autofluorescence phenotypes showing increased pRNFL thickness in this sector.This study expands the genetic landscape of RPGR-associated disease by reporting 3 novel clinically significant variants. We have shown that clinically severe phenotypes are not uncommon among female carriers. Furthermore, we provide novel insights into pRNFL changes observed in RPGR heterozygotes that mimic what has been reported in male patients.

Purpose The purpose of this study was to assess the use of topical tacrolimus ointment in preventing rejection in high-risk corneal grafts, when added to the standard immunosuppressive regimen. Methods We conducted an observational, retrospective study using clinical data of high-risk patients subjected to penetrating keratoplasty, who were treated with topical tacrolimus ointment 0.2 mg/g twice a day plus topical dexamethasone 0.1 mg/ml 6 id and compared it with a similar control group treated with topical dexamethasone 0.1 mg/ml 6 id alone. High-risk status was attributed to patients with previous ipsilateral corneal graft failure, two or more quadrants with corneal neovascularization or an infectious or inflammatory corneal disease. Results We analysed 53 patients in the trial group versus 53 patients in the control group, with similar age, baseline diagnosis and risk factors, and median follow-up times of 30 and and 24 months, respectively. Survival analysis showed a higher graft survival rate at all follow-up periods for patients treated with topical tacrolimus ( p Discussion This study shows that topical tacrolimus ointment increases the survival rate of the graft if added to the previous topical steroid regimen in high-risk patients. Conclusion Topical tacrolimus is safe and effective in prolonging graft survival in high-risk patients.

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.]

PurposeTo compare phenotypic and genetic variations in polypoidal choroidal vasculopathy (PCV) between Caucasian and Asian patients.MethodsWe 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.ResultsOne 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%, p2, pCETP 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.ConclusionAmong 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.

Infectious keratitis is an important cause of visual loss. The purpose of this study was to investigate anterior segment optical coherence tomography patterns in infectious keratitis and evaluate the role of this tool in the early management of this disorder.In this cross-sectional study, we included patients with proven infectious keratitis, either by culture or therapeutic trial. Subjects underwent baseline anterior segment optical coherence tomography (Spectralis® anterior segment module, Heidelberg Engineering, Germany) performed by the same operator. We used anterior segment optical coherence tomography vertical and horizontal raster default scans with 6.0 mm scan lines.Twenty-five patients (14 men and 11 women) were included. The most common risk factors identified were ocular trauma (11 cases) and contact lens wear (7 cases). Fifteen patients presented bacterial infection; three, fungal infection; two parasitic infection; and five cases presented a negative microbiological culture. Anterior segment optical coherence tomography depicted nine distinct morphological patterns.Anterior segment optical coherence tomography allows the depth of corneal involvement to be assessed. When the only patterns identified were hyperreflective stromal lesion and stromal edema, the visual outcome was better. Cystic spaces were present in severe bacterial keratitis.Anterior segment optical coherence tomography can complement biomicroscopy, allowing for a better characterization of corneal involvement at presentation that can help in staging and providing useful prognostic information.Introdução: As queratites infeciosas são uma causa importante de perda da acuidade visual. O objetivo deste estudo foi investigar padrões das queratites infeciosas na tomografia de coerência ótica do segmento anterior e avaliar o seu papel na orientação precoce desta patologia. Material e Métodos: Neste estudo transversal, incluímos doentes com queratite infeciosa comprovada, por cultura microbiológica ou prova terapêutica. Os doentes foram submetidos a tomografia de coerência ótica do segmento anterior na baseline (Spectralis® anterior segment module, Heidelberg Engineering, Germany) executados pelo mesmo operador. Adquiriram-se cortes verticais e horizontais de 6,0 mm com tomografia de coerência ótica spectral domain. Resultados: Foram incluídos 25 doentes (14 homens e 11 mulheres). Os fatores de risco mais comummente identificados foram o trauma ocular (11 casos) e o uso de lentes de contato (sete casos). Quinze doentes apresentaram infeção bacteriana, três infeção fúngica, dois infeção parasitária e cinco casos apresentaram culturas microbiológicas negativas. Distinguiram-se nove padrões morfológicos na tomografia de coerência ótica do segmento anterior. Discussão: A tomografia de coerência ótica do segmento anterior permite avaliar a profundidade do envolvimento corneano na queratite infeciosa. Quando os únicos padrões identificados eram a lesão estromal hiper-refletiva e edema estromal o outcome visual foi melhor. Os espaços quísticos observaram-se nas queratites bacterianas graves. Conclusão: A tomografia de coerência ótica do segmento anterior permite complementar a biomicroscopia, melhorar o estadiamento e fornecer informação prognóstica útil nas queratites infeciosas.

CNGB1 gene mutations are a well-known cause of autosomal recessive retinitis pigmentosa (RP), which was recently associated with olfactory dysfunction. The purpose of this study was to report the molecular spectrum and the ocular and olfactory phenotypes of a multiethnic cohort with CNGB1-associated RP. A cross-sectional case series was conducted at two ophthalmic genetics referral centers. Consecutive patients with molecularly confirmed CNGB1-related RP were included. All patients underwent a complete ophthalmological examination complemented by psychophysical olfactory evaluation. Fifteen patients (10 families: 8 Portuguese, 1 French, and 1 Turkish), mean aged 57.13 ± 15.37 years old (yo), were enrolled. Seven disease-causing variants were identified, two of which are reported for the first time: c.2565_2566del and c.2285G > T. Although 11/15 patients reported onset of nyctalopia before age 10, diagnosis was only established after 30 yo in 9/15. Despite widespread retinal degeneration being present in 14/15 probands, a relatively preserved visual acuity was observed throughout follow-up. Olfactory function was preserved in only 4/15 patients, all of whom carried at least one missense variant. Our study supports previous reports of an autosomal recessive RP-olfactory dysfunction syndrome in association with certain disease-causing variants in the CNGB1 gene and expands the mutational spectrum of CNGB1-related disease by reporting two novel variants.

Retinitis pigmentosa (RP) corresponds to a group of inherited retinal disorders where progressive rod-cone degeneration is observed. Cystoid macular edema (CME) and vitreomacular interface disorders (VMID) are known to complicate the RP phenotype, challenging an age-old concept of retained central visual acuity. The reported prevalence of these changes varies greatly among different studies. We aim to describe the frequency of CME and VMID and identify predictors of these changes in a cohort of Caucasian patients with genetically solved syndromic (sRP) and non-syndromic RP (nsRP).Cross-sectional study of patients with genetically solved sRP or nsRP. Genetic testing was clinically oriented in all probands and coordinated by a medical geneticist. The presence/absence of CME and VMIDs such as epiretinal membrane (ERM), vitreomacular traction (VMT), lamellar hole (LH), macular hole (MH), and macular pseudohole (MPH), and the integrity of the neurosensory retina and retinal pigment epithelium were evaluated in individual macular SD-OCT b-scans. Mixed-effects regression analysis models were used to identify significant predictors of BCVA, CME, and VMID. Significance was considered at α 0.05.We included 250 eyes from 125 patients. Mean age was 44.9 ± 15.7 years and 55.2% were male. Eighty-eight patients had nsRP and 37 had sRP. Median BCVA was 0.5 (0.2-1.3) logMAR. CME was found in 17.1% of eyes, while ERM was found in 54.3% of eyes. The frequency of CME (p = 0.45) and ERM (p = 0.07) did not differ between sRP and nsRP patients, nor across different inheritance patterns. Mixed-effects univariate linear regression identified age (p = 0.04), cataract surgery (p 0.01), and loss of integrity of outer retinal layers (p 0.01) as significant predictors of lower visual acuity, while increased foveal thickness (p 0.01) and the presence of CME (p = 0.04) were predictors of higher visual acuity. On mixed-effects multivariable analysis, only increased foveal thickness was significantly associated with better visual acuity (p 0.01).We found that the burden of ERM and CME in RP patients is high, highlighting the importance of screening for these potentially treatable conditions to improve the quality of life of RP patients.

Introduction: The purpose of this study was to compare clinical/demographic functional testing and multimodal imaging features between genetically solved and genetically unsolved nonsyndromic retinitis pigmentosa (nsRP) patients. Methods: A cross-sectional study was conducted at an inherited retinal dystrophies reference center. Consecutive patients with nsRP and available genetic testing results performed between 2018 and 2020 were included. Genetic testing was clinically oriented, and variants were classified according to the American College of Medical Genetics and Genomics. Only class IV or V variants were considered disease-causing. Clinical/demographic, functional, and imaging features were compared between genetically unsolved (G1) and genetically solved (G2) patients. Results: A total of 175 patients (146 families) were included: 68 patients (59 families) in G1 and 107 patients (87 families) in G2. First symptoms Conclusion: Individual clinical/demographic functional testing and multimodal imaging features should be considered when counseling patients about the probability of identifying disease-causing variants.

© The Royal College of Ophthalmologists 2019, 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.

PURPOSE: Genetic and epidemiologic studies have shown that lipid genes and High Density Lipoproteins (HDL) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relation to AMD in a large European dataset, and investigated whether this relationship is driven by certain sub fractions. DESIGN: (Pooled) analysis of cross-sectional data. PARTICIPANTS: 30,953 individuals aged 50+ participating in the E3 consortium; and 1530 individuals from the Rotterdam Study with lipid sub fraction data. METHODS: In E3, AMD features were graded per eye on fundus photographs using the Rotterdam Classification. Routine blood lipid measurements were available from each participant. Data on genetics, medication and confounders such as body mass index, were obtained from a common database. In a subgroup of the Rotterdam Study, lipid sub fractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random-effect were used to estimate the associations. MAIN OUTCOME MEASURES: early, late or any AMD, phenotypic features of early AMD, lipid measurements. RESULTS: HDL was associated with an increased risk of AMD, corrected for potential confounders (Odds Ratio (OR) 1.21 per 1mmol/L increase (95% confidence interval[CI] 1.14-1.29); while triglycerides were associated with a decreased risk (OR 0.94 per 1mmol/L increase [95%CI 0.91-0.97]). Both were associated with drusen size, higher HDL raises the odds of larger drusen while higher triglycerides decreases the odds. LDL-cholesterol only reached statistical significance in the association with early AMD (p=0.045). Regarding lipid sub fractions: the concentration of extra-large HDL particles showed the most prominent association with AMD (OR 1.24 [95%CI 1.10-1.40]). The CETP risk variant (rs17231506) for AMD was in line with increased-HDL levels (p=7.7x10-7); but LIPC risk variants (rs2043085, rs2070895) were associated in an opposite way (p=1.0x10-6 and 1.6x10-4). CONCLUSIONS: Our study suggests that HDL-cholesterol is associated with increased risk of AMD and triglycerides negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL sub fractions seem to be drivers in the relation with AMD, variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains a question to be answered.

N/a.

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.

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 compare the efficacy of perioperative treatment strategies, in addition to topical bromfenac 0.09% and dexamethasone 0.1%, to reduce the risk for developing cystoid macular edema (CME) after uneventful cataract surgery in diabetic patients. Setting: Twelve European study centers. Design: Randomized clinical trial. Methods: Diabetic patients having phacoemulsification cataract surgery were randomly allocated to receive no additional treatment, a subconjunctival injection with 40 mg triamcinolone acetonide, an intravitreal injection with 1.25 mg bevacizumab, or a combination of both. The main outcomes were the difference in central subfield mean macular thickness, corrected distance visual acuity, and the incidence of CME and clinically significant macular edema within 6 and 12 weeks postoperatively. Results: The study comprised 213 patients. At 6 and 12 weeks postoperatively, the central subfield mean macular thickness was 12.3 tm and 9.7 pm lower, respectively, in patients who received subconjunctival triamcinolone acetonide than patients who did not (P =.007 and P =.014, respectively). No patient who received subconjunctival triamcinolone acetonide developed CME. Intravitreal bevacizumab had no significant effect on macular thickness. Conclusions: Diabetic patients who received a subconjunctival injection with triamcinolone acetonide at the end of cataract surgery had a lower macular thickness and macular volume at 6 and 12 weeks postoperatively than patients who did not. Intravitreal bevacizumab had no significant effect. (C) 2018 ASCRS and ESCRS.

Intravitreal injections of antivascular endothelial growth factors have been considered a milestone in the treatment of neovascular age-related macular degeneration (nAMD). However, the increasing incidence of AMD and the burden of visits and injections overcharge both the patient and the healthcare systems. Real-world solutions depend on treatment protocols aimed at optimizing the number of clinical visits while guaranteeing good functional outcomes. We performed a retrospective analysis of 72 eyes from 63 naïve patients diagnosed with nAMD that underwent a fixed intravitreal protocol consisting of bimonthly injections after a three-month loading dose, with either Aflibercept or Ranibizumab (no predefined criteria for treatment selection). Best corrected visual acuity (BCVA) and optical coherence tomography were analyzed at baseline and during follow-up clinical visits (months 3, 6, 12, and 18). From the included participants, 42 followed a fixed regimen with Aflibercept and 30 with Ranibizumab. At the 12-month visit, there was not a statistically significant difference in the mean change of BCVA between the two groups (p=0.121); however, the mean difference in the central retinal thickness was significantly superior in the Aflibercept group (-142.2 versus -51.5, p=0.011). The described fixed regimen seems to be efficient in the treatment of nAMD in a clinical practice setting.

Purpose: To compare the efficacy of a topical nonsteroidal antiinflammatory drug, topical corticosteroid, and a combination of both drugs to prevent the occurrence of cystoid macular edema (CME) after cataract surgery in nondiabetic patients. Setting: Twelve European study centers. Design: Randomized clinical trial. Methods: Nondiabetic patients having uneventful cataract surgery were included in this study. Patients were randomized to receive topical bromfenac 0.09% twice daily for 2 weeks or dexamethasone 0.1% 4 times daily with 1 drop less per day every following week, or a combination of both. The primary outcome was the difference in central subfield mean macular thickness 6 weeks postoperatively. Secondary outcome measures included corrected distance visual acuity as well as the incidence of CME and clinically significant macular edema (CSME) within 6 weeks and 12 weeks postoperatively. Results: This study comprised 914 patients. Six weeks postoperatively, the central subfield mean macular thickness was 288.3 gm, 296.0 gm, and 284.5 gm in the bromfenac group, dexamethasone group, and combination treatment group, respectively (overall P = .006). The incidence of clinically significant macular edema within 12 weeks postoperatively was 3.6%, 5.1%, and 1.5%, respectively (overall P = .043). Conclusion: Patients treated with a combination of topical bromfenac 0.09% and dexamethasone 0.1% had a lower risk for developing CSME after cataract surgery than patients treated with a single drug. (C) 2018 ASCRS and ESCRS

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.

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)...

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.

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 &times, 10&minus, 2&ndash, 1.8 &times, 5), and 67 across disease stages (FDR q-value: 4.5 &times, 1.7 &times, 4). Pathway analysis showed significant enrichment of glycerophospholipid, purine, taurine and hypotaurine, and nitrogen metabolism (p-value &le, 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.

We report a case of a 41-year-old woman, wearer of contact lenses who was presented to the emergency room with a 2-month history of pain and red eye. She presented with a severe keratitis refractory to quinolones, fortified antibiotics and clotrimazole. Due to the risk of perforation, a tectonic penetrating keratoplasty (PK) was performed. Clinical signs of keratitis recurrence were observed and cultures were positive for Purpureocillium lilacinum (former Paecilomyces lilacinus). The patient did not improve on topical amphotericin B and intracameral voriconazole. Worsening of clinical condition required a new PK. Oral posaconazole was initiated postoperatively and suspended at the fourth postoperative month. The cornea remains clear until the last follow-up visit, 12 months after the second graft. To our knowledge, this is the second case report that documents the effectiveness of oral posaconazole in a refractory P. lilacinus keratitis, resistant to other second-generation triazoles and conventional antifungals.

Purpose: To determine the prevalence and risk factors related to the opacification of the LS-502-1 intraocular lens. Methods: Cross-sectional study including patients submitted to cataract surgery between January 2010 and March 2012, with implantation of the LS-502-1 intraocular lens. Past medical history was registered and a complete ophthalmologic evaluation, that included best-corrected visual acuity, slit-lamp examination and fundoscopy, was performed. Anterior segment photographs were taken whenever intraocular lens opacification was present. Results: One hundred and sixty-nine eyes of 154 patients were included, mean age 78.5 ± 7.9 years. The average follow-up after intraocular lens implantation was 65.6 ± 10.0 months. Intraocular lens opacification was seen in 53.3% (n = 90) and presented as one of four different patterns: peripheral (15.6%, n = 14), central (4.4%, n = 4), diffuse (71.1%, n = 64) and superficial white deposits (8.9%, n = 8). There was no statistically significant association with systemic or ophthalmic conditions. In patients with bilateral implantation, intraocular lens opacification in one eye was significantly related to intraocular lens opacification in the fellow eye. A significant variability in opacification was found across intraocular lens serial numbers: the odds ratio for opacification in intraocular lens with serial number beginning with 200003 was 6.0 when comparing with the remaining lenses. Conclusion: The opacification prevalence of the LS-502-1 intraocular lens was 53.3%, which is the highest ever described for any intraocular lens model. Our results suggest that this occurrence is secondary to an interaction between unknown patient variables and problems related to intraocular lens manufacturing and storage procedures.

© Springer-Verlag GmbH Germany, part of Springer Nature 2019., 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.

Copyright © 2019, Wolters Kluwer Health. Ophthalmic Communications Society, Inc., 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.

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 log-MAR. Glare testing, pupillometry, contrast sensitivity, motion, and chromatic and achromatic contrast discrimination did not differ significantly between the first and last visit (p>0.05) or when compared to an age-matched control group (p>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: To investigate systemic and ocular determinants of peripapillary retinal nerve fiber layer thickness (pRNFLT) in the European population.Design: Cross-sectional meta-analysis.Participants: A total of 16 084 European adults from 8 cohort studies (mean age range, 56.9 +/- 12.3-82.1 +/- 4.2 years) of the European Eye Epidemiology (E3) consortium.Methods: We examined associations with pRNFLT measured by spectral-domain OCT in each study using multivariable linear regression and pooled results using random effects meta-analysis.Main Outcome Measures: Determinants of pRNFLT.Results: Mean pRNFLT ranged from 86.8 +/- 21.4 mu m in the Rotterdam Study I to 104.7 +/- 12.5 mu m in the Rotterdam Study III. We found the following factors to be associated with reduced pRNFLT: Older age (beta = -0.38 mu m/year; 95% confidence interval [CI], -0.57 to -0.18), higher intraocular pressure (10P) (beta = -0.36 mu m/mmHg; 95% CI, -0.56 to -0.15), visual impairment (beta = -5.50 mu m; 95% CI, -9.37 to -1.64), and history of systemic hypertension (beta = -0.54 mu m; 95% CI, -1.01 to -0.07) and stroke (beta = -1.94 mu m; 95% CI, -3.17 to -0.72). A suggestive, albeit nonsignificant, association was observed for dementia (beta = -3.11 mu m; 95% CI, -6.22 to 0.01). Higher pRNFLT was associated with more hyperopic spherical equivalent (beta = 1.39 mu m/diopter; 95% CI, 1.19-1.59) and smoking (beta = 1.53 mu m; 95% CI, 1.00-2.06 for current smokers compared with never-smokers).Conclusions: In addition to previously described determinants such as age and refraction, we found that systemic vascular and neurovascular diseases were associated with reduced pRNFLT. These may be of clinical relevance, especially in glaucoma monitoring of patients with newly occurring vascular comorbidities. (C) 2018 by the American Academy of Ophthalmology

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.

Kabuki syndrome (KS) is a multiple congenital anomaly syndrome with diversified ophthalmological manifestations. We report a case of a boy with bilateral features of Salzmann nodular degeneration (SND) associated with KS. An 18-year-old Caucasian man with KS presented for a second opinion regarding incapacitating photophobia in his right eye, refractory to medical therapy. Biomicroscopy revealed bilateral subepithelial nodules in the midperiphery of the cornea, less extensive in the left eye, consistent with SND. Symptomatic improvement was achieved after superficial keratectomy, manually performed with a blade and adjuvant application of mitomycin C. We report a rare case of a KS patient with SND. Since KS manifestations may vary widely, it is important to perform an early ophthalmological examination for prompt detection and treatment of ocular abnormalities and thus improve life quality in these patients.

We report a case of a 41-year-old woman, wearer of contact lenses who was presented to the emergency room with a 2-month history of pain and red eye. She presented with a severe keratitis refractory to quinolones, fortified antibiotics and clotrimazole. Due to the risk of perforation, a tectonic penetrating keratoplasty (PK) was performed. Clinical signs of keratitis recurrence were observed and cultures were positive for Purpureocillium lilacinum (former Paecilomyces lilacinus). The patient did not improve on topical amphotericin B and intracameral voriconazole. Worsening of clinical condition required a new PK. Oral posaconazole was initiated postoperatively and suspended at the fourth postoperative month. The cornea remains clear until the last follow-up visit, 12 months after the second graft. To our knowledge, this is the second case report that documents the effectiveness of oral posaconazole in a refractory P. lilacinus keratitis, resistant to other second-generation triazoles and conventional antifungals.

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.Cross-sectional study.Thirty patients 3 to 4 weeks after bilateral cataract surgery with diffractive IOL implantation and 15 age- and gender-matched control subjects.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.Cortical activity (blood oxygen level dependent [BOLD] signal) in the primary visual cortex and in higher-level brain areas, including the attention network.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), P0.03). In contrast, controls showed only relative deactivation (due to lower visibility) of visual areas (occipital lobe and middle occipital gyrus, P0.03). 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 (q0.05). We found no correlation between QoV questionnaire scores and optical properties (total and higher order aberration, modulation transfer function, and Strehl ratio).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.

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.

Purpose To report the case of an anterior chamber epithelial cyst after uncomplicated deep anterior lamellar keratoplasty (DALK) treated with a tissue-sparing surgical technique. Methods A 35-year-old female patient underwent DALK in her OS because of stage IV keratoconus. The surgery was uneventful, and 3 months postoperatively, best-corrected visual acuity (BCVA) was 20/25. By the sixth postoperative month, a cystic iris lesion was noticed. The lesion grew progressively larger, and BCVA dropped to 20/63 in OS. Cyst excision was performed. Results No complications possibly related to the surgery were observed. Two years later, BCVA was 20/25 in OS, and there were no signs of cyst recurrence. Histopathological examination of the lesion showed an epithelial implantation cyst. Conclusions An anterior chamber epithelial cyst is a sight-threatening condition that may occur after DALK. In selected cases, a conservative surgical approach is an effective treatment option, conveying excellent functional and anatomical outcomes.

To report late postoperative opacification of a model of hydrophilic-hydrophobic acrylic intraocular lens (IOL) as well as the clinical consequences and laboratory characteristics.Department of Ophthalmology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.Retrospective case series.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.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.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.None of the authors has a financial or proprietary interest in any material or method mentioned.

To evaluate the clinical features of keratoconus taking into consideration anterior corneal aberrations, internal astigmatism, and corneal biomechanical properties and to define a new grading system based on visual limitation.Vissum Corporation, Alicante, Spain.Retrospective case series.This multicenter study comprised consecutive keratoconic eyes with no previous ocular surgery or active ocular disease. Visual, refractive, corneal topography, and pachymetry outcomes were analyzed. Internal astigmatism was calculated by vectorial analysis. Corneal aberrations and corneal biomechanics characterized by the Ocular Response Analyzer were evaluated in some eyes. Correlations between clinical data and a linear multiple regression analysis for characterizing the relationship between visual limitation and objective clinical data were performed.This study comprised 776 eyes of 507 patients (age range 11 to 79 years) The mean keratometry (K) correlated significantly with logMAR corrected distance visual acuity (CDVA) (r = 0.591, P.01), internal astigmatism (r = 0.497, P.01), corneal asphericity (r = -0.647, P.01), and several corneal higher-order aberrometric coefficients (r≥0.603, P.01). Significant correlations were found between some corneal aberrometric parameters and CDVA (r≥0.444, P.01). Multiple regression analysis showed that CDVA was significantly correlated with the mean K, intraocular pressure, corneal resistance factor, and spherical equivalent (r(2) = 0.69, P.01). There were significant differences in mean K, internal astigmatism, and corneal higher-order aberrations between 4 groups differentiated by visual limitation (P.01).The visual limitation in keratoconus could be explained by different alterations that occur in these corneas and allowed development of a new grading system for this condition.

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.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.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 (P0.02). The cell density in the basal layer of diabetic patients was significantly lower than in healthy controls (-15.0%, P0.0004). In the other layers, no significant differences between both groups (P0.07) were observed.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.

Human amniotic membrane has been widely used in ophthalmology for decades, particularly in ocular surface reconstruction. This article reviews its mechanism of action, surgical principles and clinical applications. The fate of transplanted amniotic membrane in the eye and its limitations will also be addressed.