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1.
Acta Diabetol ; 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802603

ABSTRACT

AIMS: To determine the presence of sectoral changes in vessel density (VD) patterns induced by vascular endothelial growth factor inhibitors (anti-VEGF) in patients with diabetic macular edema (DME) using optical coherence tomography angiography (OCTA). METHODS: Prospective, interventional study. A total of 43 patients (63 eyes) were initially enrolled in the study. We performed swept source (SS) OCT and sectorial OCTA measurement to determine parafoveal VD at baseline and after six months of anti-VEGF treatment. In the locations with statistically significant differences in VD between baseline and month 6, we performed univariate and multivariate analyses to determine which, if any, of the baseline variables were associated with the observed changes. RESULTS: A total of 34 patients (48 eyes) were included in the final analysis. Mean VD decreased from baseline to month 6 (from 45.2 (± 3.5) to 44.6 (± 3.2) % in the SCP and from 50 (± 3.3) to 49 (± 3.9) % in the DCP). The only significant changes in VD were observed in the nasal sector of the deep capillary plexus, with a decrease of 2.9% (p = 0.001). On univariate and multivariate analyses, the only variable significantly associated with changes in VD in the nasal sector after 6 months of treatment was baseline VD in the same sector. CONCLUSIONS: Anti-VEGF therapy has a small impact on VD values over time. These variations observed after treatment seems to be related to changes over areas of vascular anomalies and displaced vessels adjacent to cystic areas, with no significant changes over ischemic areas. No correlation was observed between this trend and other clinical baseline features.

2.
Diagnostics (Basel) ; 14(9)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38732293

ABSTRACT

Macular dystrophies (MDs) constitute a collection of hereditary retina disorders leading to notable visual impairment, primarily due to progressive macular atrophy. These conditions are distinguished by bilateral and relatively symmetrical abnormalities in the macula that significantly impair central visual function. Recent strides in fundus imaging, especially optical coherence tomography (OCT), have enhanced our comprehension and diagnostic capabilities for MD. OCT enables the identification of neurosensory retinal disorganization patterns and the extent of damage to retinal pigment epithelium (RPE) and photoreceptor cells in the dystrophies before visible macular pathology appears on fundus examinations. It not only helps us in diagnostic retinal and choroidal pathologies but also guides us in monitoring the progression of, staging of, and response to treatment. In this review, we summarize the key findings on OCT in some of the most common MD.

3.
Eye (Lond) ; 38(5): 841-846, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37857716

ABSTRACT

BACKGROUND/AIMS: To objectively classify eyes as either healthy or glaucoma based exclusively on data provided by peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform (GCIPL) measurements derived from spectral-domain optical coherence tomography (SD-OCT) using machine learning algorithms. METHODS: Three clustering methods (k-means, hierarchical cluster analysis -HCA- and model-based clustering-MBC-) were used separately to classify a training sample of 109 eyes as either healthy or glaucomatous using solely 13 SD-OCT parameters: pRNFL average and sector thicknesses and GCIPL average and minimum values together with the six macular wedge-shaped regions. Then, the best-performing algorithm was applied to an independent test sample of 102 eyes to derive close estimates of its actual performance (external validation). RESULTS: In the training sample, accuracy was 91.7% for MBC, 81.7% for k-means and 78.9% for HCA (p value = 0.02). The best MBC model was that in which subgroups were allowed to have variable volume and shape and equal orientation. The MBC algorithm in the independent test sample correctly classified 98 out of 102 cases for an overall accuracy of 96.1% (95% CI, 92.3-99.8%), with a sensitivity of 94.3 and 100% specificity. The accuracy for pRNFL was 92.2% (95% CI, 86.9-97.4%) and for GCIPL 98.0% (95% CI, 95.3-100%). CONCLUSIONS: Clustering algorithms in general (and MBC in particular) seem promising methods to help discriminate between healthy and glaucomatous eyes using exclusively SD-OCT-derived parameters. Understanding the relative merits of one method over others may also provide insights into the nature of the disease.


Subject(s)
Glaucoma , Tomography, Optical Coherence , Humans , Tomography, Optical Coherence/methods , Retinal Ganglion Cells , Visual Fields , Machine Learning , Algorithms
4.
J Pers Med ; 13(12)2023 Dec 16.
Article in English | MEDLINE | ID: mdl-38138945

ABSTRACT

The objective of this study was to determine the correlation between topographic vessel density (VD) and retinal thickness (RT) reductions induced by vascular endothelial growth factor inhibitors (anti-VEGF) in patients with diabetic macular edema (DME) using optical coherence tomography angiography (OCTA). This was a prospective, interventional case series. VD and RT measurements were separately taken in four parafoveal subfields at baseline and after six months of treatment. This correlation was statistically assessed using Spearman's rho correlation coefficient after adjustment for multiple comparisons. The study included a total of 48 eyes in the final analysis. Mean VD decreased from baseline to month 6 (from 45.2 (±3.5) to 44.6% (±3.2) in the superficial capillary plexus and from 50 (±3.3) to 49% (±3.9) in the deep capillary plexus). Statistically significant reductions in RT were observed in all ETDRS sectors (p < 0.0001). No significant association was found between RT and VD, even when analyzing responders and non-responders separately. After six months of anti-VEGF treatment, no significant correlation was observed between the topographic VD and RT values. These findings suggest that reductions in VD values may not solely result from a reduction in microaneurysms, also being affected by the repositioning of displaced vessels due to edema and a reduction in their caliber. Therefore, VD changes may not be a suitable indirect OCTA biomarker of microaneurysm turnover and treatment response.

6.
Biomedicines ; 11(6)2023 May 26.
Article in English | MEDLINE | ID: mdl-37371644

ABSTRACT

Geographic atrophy (GA) secondary to age-related macular degeneration is a common cause of blindness worldwide. Given the recent approval of the first therapy for GA, pegcetacoplan, we critically appraise methodological aspects of the phase 3 clinical trials published so far in this disease in relation to their design, analysis and interpretation. We reviewed some of the key attributes of all phase 3 clinical trials in GA available in the main public registry of clinical trials as of 20 May 2023. The topics discussed included types of endpoints, eligibility criteria, p-value and effect size, study power and sample size, the intention to treat principle, missing data, consistency of results, efficacy-safety balance and application of results. Five phase 3 clinical trials have reported results, either partially or completely: GATHER1, DERBY/OAKS, CHROMA/SPECTRI, SEATTLE and GATE. Although there are many similarities between these trials in terms of endpoints or broad eligibility criteria, they differ in several aspects (metric of the primary endpoint, sample size, type of adverse events, etc.) that can influence the results, which are discussed. Readers should understand key methodological aspects of clinical trials to improve their interpretation. On the other hand, authors should adhere to clinical trial reporting guidelines to communicate what was done and how it was done.

8.
Transl Vis Sci Technol ; 11(7): 14, 2022 07 08.
Article in English | MEDLINE | ID: mdl-35848905

ABSTRACT

Purpose: To clinically validate the diagnostic ability of two optical coherence tomography (OCT)-based glaucoma diagnostic calculators (GDCs). Methods: We conducted a retrospective, consecutive sampling of 76 patients with primary open-angle glaucoma, 107 glaucoma suspects, and 67 controls. Demographics, reliable visual field testing, and macular and optic disc OCT were collected. The reference diagnosis was compared against the probability of having glaucoma obtained from two GDCs derived from multivariate logistic regressions using quantitative and qualitative (GDC1) or only quantitative (GDC2) OCT data. The discrimination (area under the curve [AUC]) and calibration (calibration plots) were compared for both calculators and the best OCT parameters. Results: GDC2 was able to identify 46.9% more suspects and 14.7% more glaucomatous eyes than GDC1. Both GDCs obtained the highest discriminative ability in glaucomatous eyes (GDC1 AUC = 0.949; GDC2 = 0.943 vs inferior peripapillary retinal nerve fiber layer [pRNFL] = 0.931; P = 0.43). The discriminating ability was not as good for glaucoma suspects, but the GDCs were not inferior to pRNFL (GDC 1 AUC = 0.739; GDC2 = 0.730; inferior pRNFL = 0.760; P = 0.54) and GDC2 was still able to correctly identify up to 30.8% more cases than the conventional OCT classification. Calibration showed risk underestimation for both groups and calculators, but it was better in GDC2 and in patients with glaucoma. Conclusions: OCT-based calculators showed an excellent diagnostic performance in glaucomatous eyes. GDC2 was able to identify approximately 30% more cases than the conventional pRNFL inferior OCT classification in both groups, suggesting a potential role of these composite scores in clinical practice. Translational Relevance: These OCT-based calculators may improve glaucoma diagnosis in clinical care.


Subject(s)
Glaucoma, Open-Angle , Glaucoma , Ocular Hypertension , Glaucoma/diagnosis , Glaucoma, Open-Angle/diagnosis , Humans , Nerve Fibers , Retinal Ganglion Cells , Retrospective Studies , Tomography, Optical Coherence/methods
10.
Life (Basel) ; 12(3)2022 Mar 06.
Article in English | MEDLINE | ID: mdl-35330133

ABSTRACT

Stargardt's disease (STGD1) is caused by mutations in the ABCA4 gene. Different lesions characterised by decreased autofluorescence levels are found in fundus autofluorescence (FAF) from STGD1 patients and could be used as outcome indicators for disease progression. We investigated the fate of foci with reduced autofluorescence (FRA) within the heterogeneous background of STGD1 patients using FAF imaging. Genetically confirmed STGD1 patients presenting heterogeneous background autofluorescence on high-quality FAF images at a minimum of two visits at least 12 months apart were chosen. A grid centred on the fovea was used to define five different zones. Within each zone, five FRA were randomly selected for each eye. The eccentricity of foci was determined at different time points for each patient. Analysis of 175 randomly chosen FRA showed consistent centrifugal displacement over time, most notably in eyes showing areas with definitely decreased autofluorescence. Interestingly, FRA did not leave an area of hypo-autofluorescence on FAF in locations where they were previously located. These findings may help to better understand STGD1 progression, improve FAF interpretation, and shed light on the nature of heterogeneous background.

11.
Int J Mol Sci ; 22(19)2021 Sep 28.
Article in English | MEDLINE | ID: mdl-34638840

ABSTRACT

BACKGROUND: The aim of this study was to test the feasibility and safety of subretinal transplantation of human induced pluripotent stem cell (hiPSC)-derived retinal pigment epithelium (RPE) cells into the healthy margins and within areas of degenerative retina in a swine model of geographic atrophy (GA). METHODS: Well-delimited selective outer retinal damage was induced by subretinal injection of NaIO3 into one eye in minipigs (n = 10). Thirty days later, a suspension of hiPSC-derived RPE cells expressing green fluorescent protein was injected into the subretinal space, into the healthy margins, and within areas of degenerative retina. In vivo follow-up was performed by multimodal imaging. Post-mortem retinas were analyzed by immunohistochemistry and histology. RESULTS: In vitro differentiated hiPSC-RPE cells showed a typical epithelial morphology, expressed RPE-related genes, and had phagocytic ability. Engrafted hiPSC-RPE cells were detected in 60% of the eyes, forming mature epithelium in healthy retina extending towards the border of the atrophy. Histological analysis revealed RPE interaction with host photoreceptors in the healthy retina. Engrafted cells in the atrophic zone were found in a patchy distribution but failed to form an epithelial-like layer. CONCLUSIONS: These results might support the use of hiPSC-RPE cells to treat atrophic GA by providing a housekeeping function to aid the overwhelmed remnant RPE, which might improve its survival and therefore slow down the progression of GA.


Subject(s)
Geographic Atrophy , Induced Pluripotent Stem Cells , Retinal Pigment Epithelium , Animals , Antigens, Differentiation/biosynthesis , Disease Models, Animal , Gene Expression Regulation , Geographic Atrophy/metabolism , Geographic Atrophy/pathology , Geographic Atrophy/surgery , Heterografts , Humans , Induced Pluripotent Stem Cells/metabolism , Induced Pluripotent Stem Cells/pathology , Retinal Pigment Epithelium/metabolism , Retinal Pigment Epithelium/pathology , Retinal Pigment Epithelium/transplantation , Swine
13.
JAMA Ophthalmol ; 139(7): 743-750, 2021 Jul 01.
Article in English | MEDLINE | ID: mdl-34014262

ABSTRACT

IMPORTANCE: Treatments for geographic atrophy (GA), a late stage of age-related macular degeneration (AMD), are currently under development. Understanding the natural course is needed for optimal trial design. Although enlargement rates of GA and visual acuity (VA) in the short term are known from clinical studies, knowledge of enlargement in the long term, life expectancy, and visual course is lacking. OBJECTIVE: To determine long-term enlargement of GA. DESIGN, SETTING, AND PARTICIPANTS: In this study, participant data were collected from 4 population-based cohort studies, with up to 25 years of follow-up and eye examinations at 5-year intervals: the Rotterdam Study cohorts 1, 2, and 3 and the Blue Mountains Eye Study. Data were collected from 1990 to 2015, and data were analyzed from January 2019 to November 2020. MAIN OUTCOMES AND MEASURES: Area of GA was measured pixel by pixel using all available imaging. Area enlargement and enlargement of the square root-transformed area, time until GA reached the central fovea, and time until death were assessed, and best-corrected VA, smoking status, macular lesions according to the Three Continent AMD Consortium classification, a modified version of the Wisconsin age-related maculopathy grading system, and AMD genetic variants were covariates in Spearman, Pearson, or Mann-Whitney analyses. RESULTS: Of 171 included patients, 106 (62.0%) were female, and the mean (SD) age at inclusion was 82.6 (7.1) years. A total of 147 of 242 eyes with GA (60.7%) were newly diagnosed in our study. The mean area of GA at first presentation was 3.74 mm2 (95% CI, 3.11-4.67). Enlargement rate varied widely between persons (0.02 to 4.05 mm2 per year), with a mean of 1.09 mm2 per year (95% CI, 0.89-1.30). Stage of AMD in the other eye was correlated with GA enlargement (Spearman ρ = 0.34; P = .01). Foveal involvement was already present in incident GA in 55 of 147 eyes (37.4%); 23 of 42 eyes (55%) developed this after a mean (range) period of 5.6 (3-12) years, and foveal involvement did not develop before death in 11 of 42 eyes (26%). After first diagnosis, 121 of 171 patients with GA (70.8%) died after a mean (SD) period of 6.4 (5.4) years. Visual function was visually impaired (less than 20/63) in 47 of 107 patients (43.9%) at last visit before death. CONCLUSIONS AND RELEVANCE: In this study, enlargement of GA appeared to be highly variable in the general population. More than one-third of incident GA was foveal at first presentation; those with extrafoveal GA developed foveal GA after a mean of 5.6 years. Future intervention trials should focus on recruiting those patients who have a high chance of severe visual decline within their life expectancy.


Subject(s)
Geographic Atrophy , Macular Degeneration , Death , Female , Fluorescein Angiography , Geographic Atrophy/diagnosis , Humans , Macular Degeneration/diagnosis , Male , Prospective Studies , Visual Acuity
14.
Graefes Arch Clin Exp Ophthalmol ; 259(9): 2771-2781, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33907888

ABSTRACT

PURPOSE: To evaluate the efficacy and safety profile of Kahook Dual Blade ab interno trabeculectomy combined with phacoemulsification compared to stand-alone conventional cataract surgery. METHODS: A single-center longitudinal, randomized controlled trial was conducted. Patients older than 18 years with coexisting cataract and open-angle glaucoma or ocular hypertension were invited to participate. Preoperative and postoperative clinical data were collected and analyzed preoperatively and at months 1, 3, 6, and 12 after the procedure. Main outcome measures included best corrected visual acuity, intraocular pressure, number of glaucoma medications, endothelial cell count, and standard automated perimetry. RESULTS: Forty-two eyes from 33 patients were randomly allocated to the combined cataract and KDB (treatment, n = 21) or cataract alone (control, n = 21) groups. Intraocular pressure decreased from 17.9 ± 3.5 to 16.0 ± 2.2 mmHg and from 17.3 ± 2.5 to 15 ± 3.2 mmHg at the last visit in the treatment and control groups (p = 0.47). The use of glaucoma medications was reduced from a median (IQR) 1 (1-2) to 0 (0-0) in the treatment group and from 1 (1-2) to 0 (0-1) in the control group, with no significant differences between groups at the 12-month visit (p = 0.47). Best corrected visual acuity, endothelial cell count, and standard automated perimetry remained similar during follow-up in both groups. CONCLUSIONS: In patients with well-controlled, mild-to-moderate glaucoma, adding ab interno trabeculectomy with KDB to phacoemulsification might not be more effective than phacoemulsification alone to reach mid-teens IOP values. Both procedures showed similar safety profiles. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04202562, December 17, 2019 retrospectively registered.


Subject(s)
Glaucoma, Open-Angle , Phacoemulsification , Trabeculectomy , Adolescent , Glaucoma, Open-Angle/surgery , Humans , Intraocular Pressure , Retrospective Studies , Treatment Outcome , Visual Acuity
15.
Br J Ophthalmol ; 105(4): 496-501, 2021 04.
Article in English | MEDLINE | ID: mdl-32493759

ABSTRACT

BACKGROUND/AIMS: To identify objective glaucoma-related structural features based on peripapillary (p) and macular (m) spectral domain optical coherence tomography (SD-OCT) parameters and assess their discriminative ability between healthy and glaucoma patients. METHODS: Two hundred and sixty eyes (91 controls and 169 glaucoma) were included in this prospective study. After a complete examination, all participants underwent the posterior pole and the peripapillary retinal nerve fibre layer (pRNFL) protocols of the Spectralis SD-OCT. Principal component analysis (PCA), a data reduction method, was applied to identify and characterise the main information provided by the ganglion cell complex (GCC). The discriminative ability between healthy and glaucomatous eyes of the first principal components (PCs) was compared with that of conventional SD-OCT parameters (pRNFL, macular RNFL (mRNFL), macular ganglion cell layer (mGCL)and macular inner plexiform layer (mIPL)) using 10-fold cross-validated areas under the curve (AUC). RESULTS: The first PC explained 58% of the total information contained in the GCC and the pRNFL parameters and was the result of a general combination of almost all variables studied (diffuse distribution). Other PCs were driven mainly by pRNFL and mRNFL measurements. PCs and pRNFL had similar AUC (0.95 vs 0.96, p=0.88), and outperformed the other structural measurements: mRNFL (0.91, p=0.002), mGCL (0.92, p=0.02) and mIPL (0.92, p=0.0001). CONCLUSIONS: PCA identified a diffuse representation of the papillary and macular SD-OCT parameters as the most important PC to summarise structural data in healthy and glaucomatous eyes. PCs and pRNFL parameters showed the greatest discriminative ability between healthy and glaucoma cases.


Subject(s)
Glaucoma/diagnosis , Optic Disk/pathology , Principal Component Analysis/methods , Retinal Ganglion Cells/pathology , Tomography, Optical Coherence/methods , Cross-Sectional Studies , Female , Follow-Up Studies , Glaucoma/physiopathology , Humans , Intraocular Pressure/physiology , Male , Middle Aged , Nerve Fibers/pathology , Prospective Studies , ROC Curve
16.
Ophthalmology ; 128(11): 1604-1617, 2021 11.
Article in English | MEDLINE | ID: mdl-32717343

ABSTRACT

PURPOSE: To develop a genotype assay to assess associations with common and rare age-related macular degeneration (AMD) risk variants, to calculate an overall genetic risk score (GRS), and to identify potential misdiagnoses with inherited macular dystrophies that mimic AMD. DESIGN: Case-control study. PARTICIPANTS: Individuals (n = 4740) from 5 European cohorts. METHODS: We designed single-molecule molecular inversion probes for target selection and used next generation sequencing to sequence 87 single nucleotide polymorphisms (SNPs), coding and splice-site regions of 10 AMD-(related) genes (ARMS2, C3, C9, CD46, CFB, CFH, CFI, HTRA1, TIMP3, and SLC16A8), and 3 genes that cause inherited macular dystrophies (ABCA4, CTNNA1, and PRPH2). Genetic risk scores for common AMD risk variants were calculated based on effect size and genotype of 52 AMD-associated variants. Frequency of rare variants was compared between late AMD patients and control individuals with logistic regression analysis. MAIN OUTCOME MEASURES: Genetic risk score, association of genetic variants with AMD, and genotype-phenotype correlations. RESULTS: We observed high concordance rates between our platform and other genotyping platforms for the 69 successfully genotyped SNPs (>96%) and for the rare variants (>99%). We observed a higher GRS for patients with late AMD compared with patients with early/intermediate AMD (P < 0.001) and individuals without AMD (P < 0.001). A higher proportion of pathogenic variants in the CFH (odds ratio [OR] = 2.88; P = 0.006), CFI (OR = 4.45; P = 0.005), and C3 (OR = 6.56; P = 0.0003) genes was observed in late AMD patients compared with control individuals. In 9 patients, we identified pathogenic variants in the PRPH2, ABCA4, and CTNNA1 genes, which allowed reclassification of these patients as having inherited macular dystrophy. CONCLUSIONS: This study reports a genotype assay for common and rare AMD genetic variants, which can identify individuals at intermediate to high genetic risk of late AMD and enables differential diagnosis of AMD-mimicking dystrophies. Our study supports sequencing of CFH, CFI, and C3 genes because they harbor rare high-risk variants. Carriers of these variants could be amendable for new treatments for AMD that currently are under development.


Subject(s)
DNA/genetics , Eye Proteins/genetics , Genetic Predisposition to Disease , Macular Degeneration/genetics , Polymorphism, Single Nucleotide , Aged , Aged, 80 and over , Case-Control Studies , Eye Proteins/metabolism , Genotype , Humans , Macular Degeneration/diagnosis , Macular Degeneration/metabolism , Male , Middle Aged , Phenotype , Risk Factors
17.
Retin Cases Brief Rep ; 15(6): 778-782, 2021 Nov 01.
Article in English | MEDLINE | ID: mdl-31274850

ABSTRACT

BACKGROUND/PURPOSE: To describe a case study that shows a possible association between the slow growth rate of macular atrophy and the presence of underlying mature, nonexudative choroidal neovascularization. METHODS: Case report. PATIENT: An 82-year-old woman with mixed age-related macular degeneration in both eyes was followed up for 6 years, with the last ranibizumab treatment given in the left eye more than 2 years previously. Evaluations included fluorescein angiography, spectral-domain optical coherence tomography, and optical coherence tomography angiography. RESULTS: During follow-up, there was a peculiar growth of macular atrophy, involving mainly the superior nasal sector. No signs of exudation on fluorescein angiography or spectral-domain optical coherence tomography were apparent throughout this period. However, optical coherence tomography angiography showed a mature, nonexudative choroidal neovascularization under the foveal sparing area and surrounding all the boundaries of atrophy except in the superonasal sector. Macular atrophy growth was observed mainly in the region devoid of blood vessels. CONCLUSION: Growth of macular atrophy was more prominent in the region where mature, nonexudative choroidal neovascularization was absent. Nutrients provided by vessels from choroidal neovascularization may provide support to adjacent retinal pigment epithelium cells, slowing down the progression of atrophy.


Subject(s)
Choroidal Neovascularization , Macular Degeneration , Aged, 80 and over , Choroidal Neovascularization/diagnostic imaging , Female , Fluorescein Angiography , Humans , Macular Degeneration/diagnostic imaging , Macular Degeneration/pathology , Tomography, Optical Coherence
18.
J Ophthalmol ; 2020: 9457457, 2020.
Article in English | MEDLINE | ID: mdl-33014447

ABSTRACT

PURPOSE: This study aims to find out which tool, fundus autofluorescence (FAF) or spectral domain optical coherence tomography (SD-OCT), is more sensitive in detecting retinal pigment epithelium (RPE) demise overlying drusen and can, therefore, help predict geographic atrophy (GA) appearance in Age-Related Macular Degeneration (AMD). METHODS: A single-site, retrospective, observational, longitudinal study was conducted. Patients with intermediate AMD (iAMD) (large (>125 µm) or intermediate (63-125 µm) drusen with hyper/hypopigmentation) with a minimum follow-up of 18 months were included. Drusen with overlying incipient RPE atrophy were identified on SD-OCT defined as choroidal hypertransmission or nascent geographic atrophy (nGA). These selected drusen were, then, traced backwards in time to determine if incipient RPE atrophy overlying drusen was observed on FAF (well-demarcated region of absence of autofluorescence) before, simultaneously, or after having detected the first signs of incipient RPE atrophy on SD-OCT. The number of drusen in which signs of incipient RPE atrophy was detected earlier using FAF or SD-OCT was compared. The time elapsed from the identification with the more sensitive method to the other was recorded and analyzed. RESULTS: One hundred and thirty-three drusen in 22 eyes of 22 patients were included. Of these, 112 (84.2%) drusen showed choroidal hypertransmission and 21(15.8%) nGA. Early signs of atrophy overlying drusen were found simultaneously on SD-OCT and FAF in 52 cases (39.1%, 95% CI 30.8-47.9%), earliest on FAF in 51 (38.3%, 95% CI 30.0-47.2%) and first on SD-OCT in 30 (22.6%, 95% CI 15.8-30.6%; p < 0.05). Statistically significant differences were found between both techniques (p=0.005), with FAF detecting it earlier than SD-OCT. When RPE atrophy was found first on FAF, the median time to diagnosis with SD-OCT was 6.6 months (95% CI 5.5 to 8.6), while if detection occurred earlier on SD-OCT, the median time until identification with FAF was 12.6 months (95% CI 6.0 to 23.4; p=0.0003). CONCLUSIONS: In iAMD cases in which early atrophy overlying drusen is not detected simultaneously in FAF and SD-OCT, FAF was significantly more sensitive. Nevertheless, a multimodal approach is recommended and required to evaluate these patients.

19.
Ophthalmol Retina ; 4(12): 1129-1137, 2020 12.
Article in English | MEDLINE | ID: mdl-32371126

ABSTRACT

PURPOSE: Geographic atrophy (GA) secondary to age-related macular degeneration is considered a single entity. This study aimed to determine whether GA subgroups exist that can be defined by their genotype and phenotype. DESIGN: Retrospective analysis of cross-sectional data. PARTICIPANTS: Individuals (196 eyes of 196 patients) 50 years of age or older with GA from the EYE-RISK database. METHODS: Participants were graded for the presence of each of the following fundus features on color fundus photography: large soft drusen, reticular pseudodrusen (RPD), refractile drusen, hyperpigmentation, location of atrophy (foveal vs. extrafoveal), and multifocal lesions. Genotypes of 33 single nucleotide polymorphisms previously assigned to the complement, lipid metabolism, or extracellular matrix (ECM) pathways and ARMS2 also were included, and genetic risk scores (GRSs) for each of those 3 pathways were calculated. Hierarchical cluster analysis was used to determine subgroups of participants defined by these features. The discriminative ability of genotype, phenotype, or both for each subgroup was determined with 10-fold cross-validated areas under the receiver operating characteristic curve (cvAUCs), and the agreement between predicted and actual subgroup membership was assessed with calibration plots. MAIN OUTCOME MEASURES: Identification and characterization of GA subgroups based on their phenotype and genotype. RESULTS: Cluster analyses identified 3 subgroups of GA. Subgroup 1 was characterized by high complement GRS, frequently associated with large soft drusen and foveal atrophy; subgroup 2 generally showed low GRS, foveal atrophy, and few drusen (any type); and subgroup 3 showed a high ARMS2 and ECM GRS, RPD, and extrafoveal atrophy. A high discriminative ability existed between subgroups for the genotype (cvAUC, ≥0.94), and a modest discriminative ability existed for the phenotype (cvAUC, <0.65), with good calibration. CONCLUSIONS: We identified 3 GA subgroups that differed mostly by their genotype. Atrophy location and drusen type were the most relevant phenotypic features.


Subject(s)
Eye Proteins/genetics , Fluorescein Angiography/methods , Fovea Centralis/pathology , Geographic Atrophy/genetics , Macular Degeneration/genetics , Polymorphism, Single Nucleotide , Aged , Aged, 80 and over , Cross-Sectional Studies , Eye Proteins/metabolism , Female , Fundus Oculi , Genotype , Geographic Atrophy/diagnosis , Humans , Macular Degeneration/diagnosis , Male , Middle Aged , Phenotype , Retrospective Studies
20.
J Ophthalmol ; 2020: 1682463, 2020.
Article in English | MEDLINE | ID: mdl-32025344

ABSTRACT

PURPOSE: To analyse the vascular density of the choroid in a keratoconus (KC) population using swept-source optical coherence tomography (SS-OCT). METHODS: Prospective, noninterventional study that analysed 97 eyes from 52 KC patients and 145 eyes from 89 healthy controls. The sample was divided in four different age groups. Inclusion criteria were topographic diagnosis of KC using Pentacam, axial length shorter than 26 mm, good quality of the images, and no other systemic or ocular diseases. A 12 mm horizontal single-line SS-OCT b-scan was performed to create a choroidal thickness (CT) profile. Validated automated segmentation and binarization were used in order to analyse choroidal, stromal, and vascular areas. RESULTS: The percentage of choroidal vascularity (vascular area/total area) was 56.6% in KC patients vs. 49.4% in controls. Aged-adjusted choroidal, stromal, and vascular areas and corrected choroidal percentage of vascularity are statistically increased in KC patients when compared with healthy controls (p < 0.001). All these parameters show a decreasing trend with age. Both stromal and vascular areas were thicker in KC patients (p < 0.001). CONCLUSIONS: Choroidal, stromal, and vascular areas and corrected choroidal percentage of vascularity are statistically increased in KC patients when compared with healthy controls. All these parameters tend to decrease with age.

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