ResearchPad - retinal-disorders https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Prospective evaluation of changes in choroidal vascularity index after half-dose photodynamic therapy versus micropulse laser treatment in chronic central serous chorioretinopathy]]> https://www.researchpad.co/article/elastic_article_9783 To assess whether treatment of chronic central serous chorioretinopathy (cCSC) with photodynamic therapy (PDT) and high-density subthreshold micropulse laser (HSML) results in choroidal vascularity index (CVI) changes that may account for the treatment effect.MethodsPatients with cCSC were prospectively included and analyzed. Patients received either half-dose PDT or HSML treatment. CVI of the affected and unaffected eye was obtained before treatment, 6 to 8 weeks after treatment, and 7 to 8 months after treatment.ResultsAt baseline, 29 eyes (29 patients) were included both in the PDT and in the HSML group. The mean (± standard deviation) CVI change in the HSML group between before PDT and 6 to 8 weeks after PDT was − 0.009 ± 0.032 (p = 0.127), whereas this was 0.0025 ± 0.037 (p = 0.723) between the visit before PDT and final visit. The patients in the PDT group had a CVI change of − 0.0025 ± 0.037 (p = 0.723) between the visit before PDT and first visit after PDT, and a mean CVI change of − 0.013 ± 0.038 (p = 0.080) between the visit before PDT and final visit. There was no significant correlation between CVI and BCVA at the measured time points, in both the HSML group (p = 0.885), and in the PDT group (p = 0.904). Moreover, no significant changes in CVI occurred in the unaffected eye at any time point.ConclusionsPDT and HSML do not significantly affect CVI, and therefore a CVI change may not be primarily responsible for the treatment effect. The positive treatment effect of both interventions may rely on other mechanisms, such as an effect on choriocapillaris and/or retinal pigment epithelium function. ]]> <![CDATA[The qualitative assessment of optical coherence tomography and the central retinal sensitivity in patients with retinitis pigmentosa]]> https://www.researchpad.co/article/elastic_article_7697 To analyze the relationships between qualitative and quantitative parameters of spectral-domain optical coherence tomography (SD-OCT) and the central retinal sensitivity in patients with retinitis pigmentosa (RP).Materials and methodsNinety-three eyes of 93 patients were finally enrolled, with a median age (quartile) of 58 (24.5) years. We assessed the patients using SD-OCT and the 10–2 program of a Humphry Field Analyzer (HFA). As a qualitative parameter, two graders independently classified the patients’ SD-OCT images into five severity grades (grades 1–5) based on the severity of damage to the photoreceptor inner and outer segments (IS/OS) layer. As quantitative parameters, we measured the IS-ellipsoid zone (IS-EZ) width, IS/OS thickness, outer nuclear layer (ONL) thickness, central macular thickness (CMT, 1 and 3 mm) and macular cube (6 × 6 mm) volume and thickness. The central retinal sensitivity was defined by the best-corrected visual acuity (BCVA; logMAR), average sensitivities of the central 4 (foveal sensitivity [FS]) and 12 (macular sensitivity [MS]) points of the HFA 10–2 program and the mean deviation (MD) of the 10–2 program. Spearman’s correlation was used to assess the association between both qualitative and quantitative parameters and variables of the central retinal sensitivity. In addition, we performed a multiple regression analysis using these parameters to identify the parameters most strongly influencing the central retinal sensitivity.ResultsThe IS/OS severity grade was significantly correlated with the BCVA (ρ = 0.741, P < 0.001), FS (ρ = −0.844, P < 0.001), MS (ρ = −0.820, P < 0.001) and MD (ρ = −0.681, P < 0.001) and showed stronger correlations to them than any other quantitative parameters including the IS-EZ width, IS/OS thickness, ONL thickness, CMTs and macular cube volume/thickness. Furthermore, a step-wise multiple regression analysis indicated that the IS/OS severity grade was more strongly associated with the BCVA (β = 0.659, P < 0.001), FS (β = −0.820, P < 0.001), MS (β = −0.820, P < 0.001) and MD (β = −0.674, P < 0.001) than any other quantitative parameters. The intraclass correlation coefficient between two graders indicated substantial correlation (κ = 0.70).DiscussionThe qualitative grading of OCT based on the severity of the IS/OS layer was simple and strongly correlated with the central retinal sensitivity in patients with RP. It may be useful to assess the central visual function in patients with RP, although there is some variation in severity within the same severity grade. ]]> <![CDATA[The association of choroidal structure and its response to anti-VEGF treatment with the short-time outcome in pachychoroid neovasculopathy]]> https://www.researchpad.co/article/5c6f14b7d5eed0c48467a726

Pachychoroid neovasculopathy (PNV) shares some anatomical features with other pachychoroid spectrum diseases, but little is known about the characteristics on the treatment with anti-vascular endothelial growth factor (VEGF). We investigated the effect of choroidal structure and responses to anti-VEGF on the prognosis of pachychoroid neovasculopathy (PNV) and other types of neovascular age-related macular degeneration (non-PNV). Twenty-one eyes with PNV and 34 eyes with non-PNV who had anti-VEGF treatment were retrospectively reviewed. Choroidal neovascularization (CNV) area at baseline was measured with fluorescein angiography (FAG). The luminal and stromal area in the choroid was measured by enhanced-depth-imaging (EDI) OCT at baseline and 1 month. The association between dry macula or LogMAR VA (visual acuity, VA) at 1 month and baseline values or changes in the luminal or stromal area at 1 month, baseline CNV area, or anti-VEGF drugs were analyzed in patients with or without PNV. In non-PNV, change of luminal area (coefficient = 7.0×10−5, p = 0.0001), baseline CNV area (coefficient = 0.18, p = 0.033), and aflibercept vs. ranibizumab (coefficient = 0.29, p = 0.0048) were chosen as predictors for dry macula by the model selection. Similarly, in non-PNV, change of luminal area (coefficient = 6.1×10−6, p = 0.033), baseline CNV area (coefficient = 0.034, p = 0.022), and aflibercept vs. ranibizumab (coefficient = 0.056, p = 0.0020) were chosen as predictors for greater VA improvement. In PNV, however, none of these factors was chosen as predictors for dry macula or VA improvement by the model selection. The result of the present study implied that structural response after anti-VEGF might be different between non-PNV and PNV in the treatment with anti-VEGF agents.

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<![CDATA[Natural evolution of ductus arteriosus with noninterventional conservative management in extremely preterm infants born at 23-28 weeks of gestation]]> https://www.researchpad.co/article/5c6dc9e3d5eed0c48452a424

This study aimed to determine the natural course of patent ductus arteriosus (PDA) with noninterventional conservative management and whether the presence and/or prolonged duration of hemodynamically significant (HS) PDA increased the risk of mortality and morbidities in extremely preterm (EPT) infants. We retrospectively reviewed the medical records of EPT infants born at 23–28 weeks of gestation (n = 195) from January 2011 to June 2014, when PDA was managed with noninterventional conservative treatment. We stratified infants into three subgroups of 23–24, 25–26, and 27–28 weeks and analyzed the prevalence and natural evolution of HS PDA, defined as ventilator dependency and PDA size ≥2 mm. Multivariate regression analyses determined if the presence and/or prolonged duration of HS PDA increased the risk for mortality and/or morbidities. The overall incidence of HS PDA was 57% (111/195) at the end of the first postnatal week. In subgroup analyses, infants with 23–24 weeks of gestation had the highest incidence (93%, 50/54), with 64% (47/74) for 25–26 weeks and 21% (14/67) for 27–28 weeks. Six (5%) of 111 infants with HS PDA were discharged without ductus closure, 4 had spontaneous PDA closure on follow up, and device closure was performed for 2 infants. In the multivariate analyses, the presence or prolonged duration (per week) of HS PDA was not associated with the risk of mortality and/or morbidities. Spontaneous closure of HS PDA was mostly achieved, even in EPT infants, with a noninterventional conservative approach. In conclusion, our data showed the incidence and natural course of HS PDA in EPT infants and suggested that the presence or prolonged duration of HS PDA might not increase the rate of mortality or morbidities.

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<![CDATA[Preoperative estimation of distance between retinal break and limbus with wide-field fundus imaging: Potential clinical utility for conventional scleral buckling]]> https://www.researchpad.co/article/5c6c75add5eed0c4843cffdf

Objective

Accurate scleral marking of retinal breaks is essential for successful scleral buckling. This study aimed to investigate the use of wide-field fundus images obtained with an Optos for preoperative estimation of the distance from the limbus to the retinal breaks.

Methods and analysis

This is a retrospective review of 29 eyes from 26 patients with rhegmatogenous retinal detachment who received scleral buckling with anatomically successful repair. They underwent wide-field fundus photography with Optos California. In the pre- and postoperative fundus images, we measured distances from the macula to the retinal tears (TM), to the center of the vortex veins (VM), to the optic disc (DM), and to the posterior edge of the scleral buckle (BM).

Results

(BM—VM) / DM was significantly correlated with the distance from the limbus to the posterior edge of the scleral buckle that had been determined intraoperatively. (r = 0.705; p<0.001) We applied a regression line derived from this correlation with the value of (TM -VM) / DM in order to calculate estimated distances between retinal breaks and the limbus. The calculated distances were all within the range of distances from the limbus to the anterior and posterior edges of the scleral buckles.

Conclusion

Preoperative analysis of Optos images may be useful for estimating the distance from the limbus to retinal breaks, which might aid scleral marking during scleral buckling surgery.

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<![CDATA[Impact of different stages of intrauterine inflammation on outcome of preterm neonates: Gestational age-dependent and -independent effect]]> https://www.researchpad.co/article/5c6730e6d5eed0c484f382c7

Objective

To investigate the impact of different stages of intrauterine inflammation (IUI) on neonatal outcomes, before and after adjusting for gestational age (GA) and other perinatal confounders.

Methods

This was an observational, prospective, single-center cohort study including all eligible neonates with GA < 35 weeks and/or birth weight ≤ 1500 g born at a 3rd level Neonatal Intensive Care Unit between 2011 and 2014. Pathological patterns of placenta, membranes and cord were classified according to Redline’s criteria. Multivariable linear and logistic regression models were applied, either including or not GA among the covariates.

Results

Of the 807 enrolled neonates, 134 (16.6%) had signs of IUI: among these, 54.5% showed just histological chorioamnionitis (HCA), 25.4% had HCA + funisitis (FUN) stage 1, and 20.1% had HCA + FUN stage 2–3. At univariate analysis, HCA increased the risk for retinopathy of prematurity (ROP) and bronchopulmonary dysplasia, while FUN (any stage) had a deleterious impact on all outcomes investigated. After adjustment for covariates not including GA, HCA was a risk factor only for ROP (OR = 2.8, CI: 1–7.8), while FUN (any stage) was still associated with increased ORs for all outcomes (p <0.01). Upon inclusion of GA in the regression model, the results differed remarkably. HCA was associated with lower risk for mechanical ventilation (OR = 0.3, CI: 0.1–0.7) and need for surfactant (OR = 0.5, CI: 0.2–0.9), while FUN (any stage) worsened clinical conditions at birth (p <0.05), increased the risk for early-onset sepsis (p <0.01), and increased the length of mechanical ventilation (FUN stage 2–3 only, RC = 6.5 days, CI: 2–11). No other outcome was affected.

Conclusions

IUI, especially FUN, negatively impact most neonatal morbidities, but its effect is partially reverted adjusting for GA. Considered that GA is an intermediate variable interposed between prenatal causes of prematurity and outcomes, the appropriateness of adjusting for GA may be questionable.

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<![CDATA[Second-line glucose-lowering drugs added to metformin and the risk of hospitalization for heart failure: A nationwide cohort study]]> https://www.researchpad.co/article/5c6b26a1d5eed0c484289d9a

Aim

To compare the risks of hospitalization for heart failure (HHF) associated with sulfonylurea (SU), dipeptidyl peptidase-4 inhibitor (DPP-4i), and thiazolidinedione (TZD) as add-on medications to metformin (MET) therapy using the data of Korean adults with type-2 diabetes from the Korean National Health Insurance database.

Methods

We identified 98,383 people who received SU (n = 42,683), DPP-4i (n = 50,310), or TZD (n = 5,390) added to initial treatment of MET monotherapy in patients with type-2 diabetes. The main outcome was the hospitalization for HHF. Hazard ratios for HHF by type of second-line glucose-lowering medication were estimated by Cox-proportional hazard models. Sex, age, duration of MET monotherapy, Charlson Comorbidity Index and additional comorbidities, and calendar year were controlled as potential confounders.

Results

The observed numbers (rate per 100,000 person-years) of HHF events were 1,129 (658) for MET+SU users, 710 (455) for MET+DPP-4i users, and 110 (570) for MET+TZD users. Compared to that for MET+SU users (reference group), the adjusted hazard ratios for HHF events were 0.76 (95% confidence interval 0.69–0.84) for MET+DPP-4i users and 0.96 (95% confidence interval 0.79–1.17) for MET+TZD users.

Conclusion

DPP-4i as an add-on therapy to MET may lower the risks of HHF compared with SU.

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<![CDATA[Axial length and its associations in a Russian population: The Ural Eye and Medical Study]]> https://www.researchpad.co/article/5c5df355d5eed0c484581168

Purpose

To assess the normal distribution of axial length and its associations in a population of Russia.

Methods

The population-based Ural Eye and Medical Study included 5,899 (80.5%) individuals out of 7328 eligible individuals aged 40+ years. The participants underwent an ocular and systemic examination. Axial length was measured sonographically (Ultra-compact A/B/P ultrasound system, Quantel Medical, Cournon d'Auvergne, France).

Results

Biometric data were available for 5707 (96.7%) individuals with a mean age of 58.8±10.6 years (range:40–94 years; 25%, 50%, 75% quartile: 51.0, 58.0, 66.0 years, respectively). Mean axial length was 23.30±1.10 mm (range: 19.02–32.87mm; 95% confidence interval (CI): 21.36–25.89; 25%, 50%, 75% quartile: 22.65mm, 23.23mm, 23.88mm, resp.). Prevalences of moderate myopia (axial length:24.5-<26.5mm) and high myopia (axial length >26.5mm) were 555/5707 (8.7%;95%CI:9.0,10.5) and 78/5707 (1.4%;95%CI:1.1,1.7), respectively. Longer axial length (mean:23.30±1.10mm) was associated (correlation coefficient r2:0.70) with older age (P<0.001;standardized regression coefficient beta:0.14), taller body height (P<0.001;beta:0.07), higher level of education (P<0.001;beta:0.04), higher intraocular pressure (P<0.001;beta:0.03), more myopic spherical refractive error (P<0.001;beta:-0.55), lower corneal refractive power (P<0.001;beta:-0.44), deeper anterior chamber depth (P<0.001;beta:0.20), wider anterior chamber angle (P<0.001;beta:0.05), thinner peripapillary retinal nerve fiber layer thickness (P<0.001;beta:-0.04), higher degree of macular fundus tessellation (P<0.001;beta:0.08), lower prevalence of epiretinal membranes (P = 0.01;beta-0.02) and pseudoexfoliation (P = 0.007;beta:-0.02) and higher prevalence of myopic maculopathy (P<0.001;beta:0.08). In that model, prevalence of age-related macular degeneration (any type: P = 0.84; early type: P = 0.46), diabetic retinopathy (P = 0.16), and region of habitation (P = 0.27) were not significantly associated with axial length.

Conclusions

Mean axial length in this typically multi-ethnic Russian study population was comparable with values from populations in Singapore and Beijing. In contrast to previous studies, axial length was not significantly related with the prevalences of age-related macular degeneration and diabetic retinopathy or region of habitation.

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<![CDATA[The findings of optical coherence tomography of retinal degeneration in relation to the morphological and electroretinographic features in RPE65−/− mice]]> https://www.researchpad.co/article/5c59ff13d5eed0c484135aa6

Purpose

Mutations of the gene encoding RPE65 cause Leber congenital amaurosis (LCA) retinitis pigmentosa (RP). The optical coherence tomography (OCT) is increasingly utilized to noninvasively evaluate various types of retinal diseases, including RP. The present study was conducted to characterize the OCT findings of the RPE65−/− mice—an animal model of LCA and RP—in relation to the morphological features based on histological and electron microscopic findings as well as electroretinography (ERG) features.

Materials and methods

RPE65−/− mice were employed as a model of retinal degeneration. C57BL/6J mice were used as a wild-type control. OCT was performed on the RPE65−/− mice from postnatal day (P) 22 to 170. The longitudinal changes in the OCT images and fundus pictures were analyzed both qualitatively and quantitatively in comparison to those of C57BL/6J mice. The OCT images were also compared to the histological and electron microscopic findings. Full field combined rod and cone ERG was performed to analyze the relationship between morphology based on OCT and the amplitudes of the a- and b-waves.

Results

In the RPE65−/− mice, the photoreceptor rod and cone layer appeared as a diffuse hyperreflective zone contiguous with the inner segment ellipsoid zone (IS-EZ) on OCT, even on P22, whereas the IS-EZ and interdigitation zone were clearly identified in the age-matched C57BL/6J mice. The histological analyses revealed that the regular arrangement of the photoreceptor inner and outer segments was gradually lost in the RPE65-/- mice. On electron microscopy, most of the rod outer segments were degenerated from P21 to P35, whereas outer segments became variably shorter after P49 although ultrastructure appeared to normalize. The thickness of the outer nuclear layer of RPE65−/− mice was slowly and progressively reduced in comparison to C57BL/6J mice. Although the thickness of the inner and outer segment layer of RPE65−/− mice was significantly decreased in comparison to C57BL/6J mice, the change was not progressive, at least until P170. Even at P35, the amplitudes of both a- and b-waves on ERG were severely deteriorated in comparison to those of C57BL/6J mice. Mottled depigmented spots appeared throughout the fundus in RPE65−/− mice after P72, and were detected as hyperreflective deposits under the retinal pigment epithelium on OCT.

Discussion

The pathological changes in the inner and outer segments layer of RPE65−/− mice were identified as diffuse hyperreflective changes on OCT. The rod outer segments showed degeneration in the early postnatal periods but became morphologically normalized in the disc structure after P49, although the sizes of the length of the rod outer segments were variable. OCT could not qualitatively differentiate the early degeneration of rods from the late variability in size of rods. Although the morphology of the photoreceptor outer segments was relatively preserved in the RPE65−/− mice, the amplitudes of ERG were severely disturbed. These structural and functional deficits may be derived from the defective supply of 11-cis-retinol to the photoreceptors.

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<![CDATA[Neuroprotective effects of PPARα in retinopathy of type 1 diabetes]]> https://www.researchpad.co/article/5c61e91ad5eed0c48496f806

Diabetic retinopathy (DR) is a common neurovascular complication of type 1 diabetes. Current therapeutics target neovascularization characteristic of end-stage disease, but are associated with significant adverse effects. Targeting early events of DR such as neurodegeneration may lead to safer and more effective approaches to treatment. Two independent prospective clinical trials unexpectedly identified that the PPARα agonist fenofibrate had unprecedented therapeutic effects in DR, but gave little insight into the physiological and molecular mechanisms of action. The objective of the present study was to evaluate potential neuroprotective effects of PPARα in DR, and subsequently to identify the responsible mechanism of action. Here we reveal that activation of PPARα had a robust protective effect on retinal function as shown by Optokinetic tracking in a rat model of type 1 diabetes, and also decreased retinal cell death, as demonstrated by a DNA fragmentation ELISA. Further, PPARα ablation exacerbated diabetes-induced decline of visual function as demonstrated by ERG analysis. We further found that PPARα improved mitochondrial efficiency in DR, and decreased ROS production and cell death in cultured retinal neurons. Oxidative stress biomarkers were elevated in diabetic Pparα-/- mice, suggesting increased oxidative stress. Mitochondrially mediated apoptosis and oxidative stress secondary to mitochondrial dysfunction contribute to neurodegeneration in DR. Taken together, these findings identify a robust neuroprotective effect for PPARα in DR, which may be due to improved mitochondrial function and subsequent alleviation of energetic deficits, oxidative stress and mitochondrially mediated apoptosis.

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<![CDATA[Quantity and quality of image artifacts in optical coherence tomography angiography]]> https://www.researchpad.co/article/5c6448bed5eed0c484c2ed28

Objective

To analyze quality and frequency of OCTA artifacts and to evaluate their impact on the interpretability of OCTA images.

Design

75 patients with diabetic retinopathy (DR), retinal artery occlusion (RAO), retinal vein occlusion (RVO), or neovascular age-related macular degeneration (nAMD) and healthy controls were enrolled in this cross-sectional study in the outpatient department of a tertiary eye care center.

Methods

All participants underwent an OCTA examination (spectral domain OCT Cirrus 5000 equipped with the AngioPlex module). OCTA scans were analyzed independently by two experienced ophthalmologists. Frequency of various artifacts for the entire OCTA scan and for different segmentation layers and the grading of OCTA interpretability were investigated.

Results

The analysis of 75 eyes of 38 women and 37 men between 24 and 94 years were included. Six eyes had no retinal disease, 19 eyes had nAMD, 16 had DR, 19 eyes had RVO, and 15 eyes showed RAO. A macular edema (ME) was present in 40 of the diseased eyes. Projection artifacts occurred in all eyes in any structure below the superficial retinal vessel layer, segmentation and motion artifacts were found in 55% (41/75) and 49% (37/75) of eyes, respectively. Other artifacts occurred less frequently. Segmentation artifacts were significantly more frequent in diseased than in healthy eyes (p<0.01). Qualitative assessment of OCTA images was graded as excellent in 65% and sufficient in 25% of cases, adding up to 91% images deemed acceptable for examination. Presence of ME was associated with a significantly poorer interpretability (p<0.01).

Conclusion and Relevance

Various artifacts appear at different frequencies in OCTA images. Nevertheless, a qualitative assessment of the OCTA images is almost always possible. Good knowledge of possible artifacts and critical analysis of the complete OCTA dataset are essential for correct clinical interpretation and determining a precise clinical diagnosis.

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<![CDATA[Does retinopathy predict stroke recurrence in type 2 diabetes patients: A retrospective study?]]> https://www.researchpad.co/article/5c605a3ad5eed0c4847ccc0b

Aims

To study if retinopathy increases the risk of stroke recurrence in stroke patients with type 2 diabetes. Also, to study if stroke patients with type 2 diabetes have an increased risk of stroke recurrence compared to non-diabetics and if stroke patients with type 2 diabetes, regardless of retinopathy, have a higher incidence of carotid stenosis. Also, to study if stroke patients with type 2 diabetes retinopathy have increased incidence of carotid stenosis.

Methods

We included 445 patients with type 2 diabetes mellitus and a matched control group of 445 patients without diabetes, who had all suffered their first stroke or TIA. Information on retinopathy, risk factors and stroke recurrence were obtained from registers and medical records.

Results

Retinopathy did not increase the risk of stroke recurrence in diabetes patients, HR 0.89 (0.51–1.53), p = 0.67. The risk of stroke recurrence was not increased in diabetics compared to non-diabetes. Diabetes patients had an increased prevalence of carotid stenosis compared to non-diabetics, 1.69 (1.15–2.48), p = 0.008. The prevalence of carotid stenosis in diabetics with retinopathy was not increased compared to diabetics without retinopathy.

Conclusion

Retinopathy is not a predictor of stroke recurrence or carotid stenosis in type 2 diabetes patients.

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<![CDATA[Molecular and clinical analysis of 27 German patients with Leber congenital amaurosis]]> https://www.researchpad.co/article/5c269745d5eed0c48470f15a

Leber congenital amaurosis (LCA) is the earliest and most severe form of all inherited retinal dystrophies (IRD) and the most frequent cause of inherited blindness in children. The phenotypic overlap with other early-onset and severe IRDs as well as difficulties associated with the ophthalmic examination of infants can complicate the clinical diagnosis. To date, 25 genes have been implicated in the pathogenesis of LCA. The disorder is usually inherited in an autosomal recessive fashion, although rare dominant cases have been reported. We report the mutation spectra and frequency of genes in 27 German index patients initially diagnosed with LCA. A total of 108 LCA- and other genes implicated in IRD were analysed using a cost-effective targeted next-generation sequencing procedure based on molecular inversion probes (MIPs). Sequencing and variant filtering led to the identification of putative pathogenic variants in 25 cases, thereby leading to a detection rate of 93%. The mutation spectrum comprises 34 different alleles, 17 of which are novel. In line with previous studies, the genetic results led to a revision of the initial clinical diagnosis in a substantial proportion of cases, demonstrating the importance of genetic testing in IRD. In addition, our detection rate of 93% shows that MIPs are a cost-efficient and sensitive tool for targeted next-generation sequencing in IRD.

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<![CDATA[Views of ophthalmologists on the genetics of age-related macular degeneration: Results of a qualitative study]]> https://www.researchpad.co/article/5c25452ad5eed0c48442c08a

Background

Age-related macular degeneration (AMD) is the leading cause of blindness in industrialized countries. It is a multifactorial disease of the retina modified by environmental/individual (e.g. smoking) and genetic factors. 34 independent genomic loci are associated with the risk to develop AMD; an interaction between smoking and genetics is currently investigated. It is unclear how the knowledge on the strong genetic component has entered the knowledge base of practicing ophthalmologists, and how they inform and counsel their (AMD) patients about it. In this study, we explore the ophthalmologists’ view on AMD genetics, and their inclination towards communicating genetic risks to patients.

Methods

We recruited a purposive sample of thirty German ophthalmologists (office based: n = 15, hospital employees: n = 15, f:8/30), who took part in a recorded semi-standardized interview. Transcripts were analyzed using content analysis.

Results

The majority of office-based ophthalmologists claimed to be unfamiliar with genetics of AMD, in contrast to hospital-affiliated ophthalmologists. Both office and hospital ophthalmologists were convinced that genetics lacks practical relevance in everyday patient care. Many withhold information on heritability or genetic background of AMD from patients and their relatives, for fear of unsettling those individuals. The relevance of the genetic component of AMD or an individuals’ high genetic risk for prevention, e.g. screening or lifestyle modifications in persons with adverse genetic profile, was rated low.

Conclusion

Developing genetic educational programs tailored to the routine care of ophthalmologists may be indicated, as well as a better two-way communication between research and practice. Exploring patient views about their expectations to being informed about genetic disease etiology, or about their individual risk, would help inform communication strategies.

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<![CDATA[Choroidal structural analysis in eyes with diabetic retinopathy and diabetic macular edema—A novel OCT based imaging biomarker]]> https://www.researchpad.co/article/5c1966e9d5eed0c484b534e7

Purpose

To evaluate structural changes in the choroid among patients with diabetic macular edema (DME), with varying grades of diabetic retinopathy (DR), using enhance depth imaging spectral domain optical coherence tomography (EDI SD-OCT) scans.

Methods

A cross-sectional study was conducted on 82 eyes with DR and DME and 86 healthy control eyes. Eyes with DME were classified according to the severity of DR as per the international DR severity scale. Sub foveal choroidal thickness (SFCT)was obtained using EDI SD-OCT scans. These scans were binarized into luminal and stromal areas, to derive the choroidal vascularity index (CVI). CVI and SFCT were analyzed between the study and control group using paired-T test. Tukey’s test was used to correlate the differences in CVI and SFCT between different grades of DR. Further analysis was done to look for the effect of DR severity and type of DME on CVI as well as SFCT using correlation coefficient and linear regression analysis.

Results

SFCT was significantly increased in eyes with DME as compared to the controls (334.47±51.81μm vs 284.53±56.45μm, p<0.001), and showed an ascending trend with worsening of DR, though this difference was not statistically significant [mild non-proliferative diabetic retinopathy (NPDR) = 304.33±40.39μm, moderate NPDR = 327.81±47.39μm, severe NPDR = 357.72±62.65μm, proliferative DR (PDR) = 334.59±47.4μm, p-0.09]. CVI was significantly decreased in DME with DR eyes as compared to controls (63.89±1.89 vs 67.51±2.86, p<0.001). CVI was also significantly decreased with worsening DR (mild NPDR = 66.38±0.3, moderate NPDR = 65.28±0.37, severe NPDR = 63.50±0.47, PDR = 61.27±0.9, p<0.001).

Conclusion

SFCT and CVI are dynamic parameters that are affected by DME. Unlike CVI, SFCT is also affected by ocular and systemic factors like edema and hypertension. CVI may be a more accurate surrogate marker for DME and DR and can potentially be used to monitor the progression of DR.

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<![CDATA[A comparison of surgical outcomes between pre-and full-term patients with exotropia]]> https://www.researchpad.co/article/5c141eadd5eed0c484d27ba2

Purpose

To compare the surgical outcomes between pre- and full-term patients with exotropia and to examine the factors associated with surgical outcomes.

Methods

This retrospective study included 48 pre- and 432 full-term patients with basic-type exotropia who underwent unilateral or bilateral lateral rectus muscle (ULR or BLR) recession. Preoperative characteristics and surgical outcomes were compared between the pre- and full-term infants. Additionally, factors affecting the surgical outcomes were evaluated in all patients.

Results

The preoperative characteristics were significantly different between the pre- and full-term groups in terms of neurodevelopmental disabilities (p = 0.020). There were no significant differences between the pre- and full-term groups in terms of the success, overcorrection, and recurrence rates after the mean follow-up period of 34.6 ± 13.9 months (p = 0.697). The major cause of surgical failure was recurrence in both groups. Pre-term birth was not a risk factor for overcorrection and recurrence. However, regardless of the pre- or full-term birth status, the presence of neurodevelopmental disabilities significantly affected final overcorrection (p = 0.004).

Conclusions

Pre-term patients with exotropia showed similar surgical outcomes to full-term controls. The presence of neurodevelopmental disabilities was a risk factor for final overcorrection.

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<![CDATA[Repeatability and reproducibility of retinal and choroidal thickness measurements in Diabetic Macular Edema using Swept-source Optical Coherence Tomography]]> https://www.researchpad.co/article/5b69466f463d7e3867f4ad0f

Purpose

To evaluate the repeatability and reproducibility of retinal and choroidal thickness measured with Swept source Optical Coherence Tomography (SS-OCT) in eyes with Diabetic Macular Edema (DME).

Methods

42 DME eyes were imaged using SS-OCT standard Macular scanning protocols. Retinal and choroidal thickness were measured in the Total macular circle (TMC) and foveal central subfield (FCS) using device-integrated specific software. The coefficient of repeatability (CR) and intraclass correlation coefficient (ICC) were determined as a measure of repeatability and relative reliability within graders. Reproducibility was assessed using Bland-Altman plots and 95% limits of agreement (LoA) were determined as a measure of interobserver variability.

Results

Intragrader CR of retinal and choroidal thickness were 8.37 and 12.20 microns for TMC and 22.24 and 32.40 microns for FCS, and intergrader 95% LoA were 7.37–8.69 and -27.2–27.71 microns for TMC and -34.21–41.93 and -30.46–24.84 for FCS, respectively. Retinal and choroidal thickness showed very good intraobserver reliability for both TMC and FCS (ICC 0.99, LoA 0.98–0.99 in all cases). Intraobserver and interobserver variability for retinal and choroidal thickness was not significantly different for TMC (p = 0.98 and p = 0.90, p = 0.98 and p = 0.91) or FCS (p = 0.97 and p = 0.85, p = 0.78 and p = 0.73), respectively.

Conclusions

Retinal and choroidal thickness in DME eyes can be quantified with good reliability, repeatability and reproducibility using new OCT devices that incorporate swept source technology. The technical advantages of this technology may provide new insights in the understanding of the choroidal changes related with DME.

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<![CDATA[Age-related macular degeneration and progression of coronary artery calcium: The Multi-Ethnic Study of Atherosclerosis]]> https://www.researchpad.co/article/5b601751463d7e3bf2e777ce

Background

Age-related macular degeneration (AMD) shares many similarities with cardiovascular disease (CVD) pathophysiology. We sought to determine the relationship of AMD to the progression of coronary artery calcium (CAC) using data from the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods

Our cohort consisted of 5803 adults aged 45 to 84 years free of known cardiovascular disease (CVD). Retinal photographs were taken during visit 2 (Aug 2002-Jan 2004). CAC was measured with computed tomography at visit 1 (July 2000-Aug 2002) and visit 5 (April 2010-Dec 2011) and changes between visits were determined.

Results

Participants were categorized as with (n = 244) and without AMD (n = 5559) at visit 2. At visit 5, 92 participants with and 2684 without AMD had CAC scores. Among those with detectable CAC at baseline (>0 at visit 1), CAC progression was greater in persons with compared to those without AMD after multivariable adjustment (530 ± 537 vs. 339 ± 426 Agatston units, P<0.01).

Conclusions

The presence of AMD in a diverse population without known clinical CVD independently predicted higher 10-year CAC progression in participants with baseline CAC >0. The retinal exam might be a useful tool for pre-clinical assessment and prevention of CVD events.

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<![CDATA[A monoclonal antibody targeting amyloid β (Aβ) restores complement factor I bioactivity: Potential implications in age-related macular degeneration and Alzheimer’s disease]]> https://www.researchpad.co/article/5b0e539c463d7e030321d286

Activation of the alternative complement cascade has been implicated in the pathogenesis of age related macular degeneration (AMD) and Alzheimer’s disease (AD). Amyloid β (Aβ), a component of drusen, may promote complement activation by inhibiting CFI bioactivity. We determined whether Aβ reduced CFI bioactivity and whether antibodies against Aβ including a monoclonal antibody, GSK933776 could restore CFI bioactivity. We also measured CFI bioactivity in plasma of subjects with AMD and AD. In support of the GSK933776 development program in AMD (geographic atrophy), we developed a quantitative assay to measure CFI bioactivity based on its ability to cleave C3b to iC3b, and repeated it in presence or absence of Aβ and anti-Aβ antibodies. Using this assay, we measured CFI bioactivity in plasma of 194 subjects with AMD, and in samples from subjects with AD that had been treated with GSK933776 as part of the GSK933776 development program in AD. Aβ reduced the CFI bioactivity by 5-fold and pre-incubation with GSK933776 restored CFI bioactivity. In subjects with AMD, plasma CFI levels and bioactivity were not significantly different from non-AMD controls. However, we detected a positive linear trend, suggesting increasing activity with disease severity. In subjects with AD, we observed a 10% and 27% increase in overall CFI bioactivity after treatment with GSK933776 during the second and third dose. Our studies indicate that CFI enzymatic activity can be inhibited by Aβ and be altered in proinflammatory diseases such as AMD and AD, in which deposition of Aβ and activation of the alternative complement cascade are believed to play a key role in the disease process.

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<![CDATA[Functional EF-Hands in Neuronal Calcium Sensor GCAP2 Determine Its Phosphorylation State and Subcellular Distribution In Vivo, and Are Essential for Photoreceptor Cell Integrity]]> https://www.researchpad.co/article/5989d9fbab0ee8fa60b722a1

The neuronal calcium sensor proteins GCAPs (guanylate cyclase activating proteins) switch between Ca2+-free and Ca2+-bound conformational states and confer calcium sensitivity to guanylate cyclase at retinal photoreceptor cells. They play a fundamental role in light adaptation by coupling the rate of cGMP synthesis to the intracellular concentration of calcium. Mutations in GCAPs lead to blindness. The importance of functional EF-hands in GCAP1 for photoreceptor cell integrity has been well established. Mutations in GCAP1 that diminish its Ca2+ binding affinity lead to cell damage by causing unabated cGMP synthesis and accumulation of toxic levels of free cGMP and Ca2+. We here investigate the relevance of GCAP2 functional EF-hands for photoreceptor cell integrity. By characterizing transgenic mice expressing a mutant form of GCAP2 with all EF-hands inactivated (EFGCAP2), we show that GCAP2 locked in its Ca2+-free conformation leads to a rapid retinal degeneration that is not due to unabated cGMP synthesis. We unveil that when locked in its Ca2+-free conformation in vivo, GCAP2 is phosphorylated at Ser201 and results in phospho-dependent binding to the chaperone 14-3-3 and retention at the inner segment and proximal cell compartments. Accumulation of phosphorylated EFGCAP2 at the inner segment results in severe toxicity. We show that in wildtype mice under physiological conditions, 50% of GCAP2 is phosphorylated correlating with the 50% of the protein being retained at the inner segment. Raising mice under constant light exposure, however, drastically increases the retention of GCAP2 in its Ca2+-free form at the inner segment. This study identifies a new mechanism governing GCAP2 subcellular distribution in vivo, closely related to disease. It also identifies a pathway by which a sustained reduction in intracellular free Ca2+ could result in photoreceptor damage, relevant for light damage and for those genetic disorders resulting in “equivalent-light” scenarios.

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