Central subfield thickness of diabetic macular edema: Correlation with the aqueous humor proteome.

Purpose: Diabetic macular edema (DME) is a sight-threatening complication of diabetes. Consequently, studying the proteome of DME may provide novel insights into underlying molecular mechanisms. Methods: In this study, aqueous humor samples from eyes with treatment-naïve clinically significant DME (n = 13) and age-matched controls (n = 11) were compared with label-free liquid chromatography-tandem mass spectrometry. Additional aqueous humor samples from eyes with treatment-naïve DME (n = 15) and controls (n = 8) were obtained for validation by enzyme-linked immunosorbent assay (ELISA). Best-corrected visual acuity (BCVA) was evaluated, and the severity of DME was measured as central subfield thickness (CST) employing optical coherence tomography. Control samples were obtained before cataract surgery. Significantly changed proteins were identified using a permutation-based calculation, with a false discovery rate of 0.05. A human donor eye with DME and a control eye were used for immunofluorescence. Results: A total of 101 proteins were differentially expressed in the DME. Regulated proteins were involved in complement activation, glycolysis, extracellular matrix interaction, and cholesterol metabolism. The highest-fold change was observed for the fibrinogen alpha chain (fold change = 17.8). Complement components C2, C5, and C8, fibronectin, and hepatocyte growth factor-like protein were increased in DME and correlated with best-corrected visual acuity (BCVA). Ceruloplasmin and complement component C8 correlated with central subfield thickness (CST). Hemopexin, plasma kallikrein, monocyte differentiation antigen CD14 (CD14), and lipopolysaccharide-binding protein (LBP) were upregulated in the DME. LBP was correlated with vascular endothelial growth factor. The increased level of LBP in DME was confirmed using ELISA. The proteins involved in desmosomal integrity, including desmocollin-1 and desmoglein-1, were downregulated in DME and correlated negatively with CST. Immunofluorescence confirmed the extravasation of fibrinogen at the retinal level in the DME. Conclusion: Elevated levels of pro-inflammatory proteins, including the complement components LBP and CD14, were observed in DME. DME was associated with the loss of basal membrane proteins, compromised desmosomal integrity, and perturbation of glycolysis.

Review and comparison of retinal vessel calibre and geometry software and their application to diabetes, cardiovascular disease, and dementia.

Developments in retinal imaging technologies have enabled the quantitative evaluation of the retinal vasculature. Changes in retinal calibre and/or geometry have been reported in systemic vascular diseases, including diabetes mellitus (DM), cardiovascular disease (CVD), and more recently in neurodegenerative diseases, such as dementia. Several retinal vessel analysis softwares exist, some being disease-specific, others for a broader context. In the research setting, retinal vasculature analysis using semi-automated software has identified associations between retinal vessel calibre and geometry and the presence of or risk of DM and its chronic complications, and of CVD and dementia, including in the general population. In this article, we review and compare the most widely used semi-automated retinal vessel analysis softwares and their associations with ocular imaging findings in common systemic diseases, including DM and its chronic complications, CVD, and dementia. We also provide original data comparing retinal calibre grading in people with Type 1 DM using two softwares, with good concordance.

Diabetic retinopathy screening in the emerging era of artificial intelligence.

Diabetic retinopathy is a frequent complication in diabetes and a leading cause of visual impairment. Regular eye screening is imperative to detect sight-threatening stages of diabetic retinopathy such as proliferative diabetic retinopathy and diabetic macular oedema in order to treat these before irreversible visual loss occurs. Screening is cost-effective and has been implemented in various countries in Europe and elsewhere. Along with optimised diabetes care, this has substantially reduced the risk of visual loss. Nevertheless, the growing number of patients with diabetes poses an increasing burden on healthcare systems and automated solutions are needed to alleviate the task of screening and improve diagnostic accuracy. Deep learning by convolutional neural networks is an optimised branch of artificial intelligence that is particularly well suited to automated image analysis. Pivotal studies have demonstrated high sensitivity and specificity for classifying advanced stages of diabetic retinopathy and identifying diabetic macular oedema in optical coherence tomography scans. Based on this, different algorithms have obtained regulatory approval for clinical use and have recently been implemented to some extent in a few countries. Handheld mobile devices are another promising option for self-monitoring, but so far they have not demonstrated comparable image quality to that of fundus photography using non-portable retinal cameras, which is the gold standard for diabetic retinopathy screening. Such technology has the potential to be integrated in telemedicine-based screening programmes, enabling self-captured retinal images to be transferred virtually to reading centres for analysis and planning of further steps. While emerging technologies have shown a lot of promise, clinical implementation has been sparse. Legal obstacles and difficulties in software integration may partly explain this, but it may also indicate that existing algorithms may not necessarily integrate well with national screening initiatives, which often differ substantially between countries.

A MULTITASK DEEP-LEARNING SYSTEM FOR ASSESSMENT OF DIABETIC MACULAR ISCHEMIA ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IMAGES.

PURPOSE: We aimed to develop and test a deep-learning system to perform image quality and diabetic macular ischemia (DMI) assessment on optical coherence tomography angiography (OCTA) images. METHODS: This study included 7,194 OCTA images with diabetes mellitus for training and primary validation and 960 images from three independent data sets for external testing. A trinary classification for image quality assessment and the presence or absence of DMI for DMI assessment were labeled on all OCTA images. Two DenseNet-161 models were built for both tasks for OCTA images of superficial and deep capillary plexuses, respectively. External testing was performed on three unseen data sets in which one data set using the same model of OCTA device as of the primary data set and two data sets using another brand of OCTA device. We assessed the performance by using the area under the receiver operating characteristic curves with sensitivities, specificities, and accuracies and the area under the precision-recall curves with precision. RESULTS: For the image quality assessment, analyses for gradability and measurability assessment were performed. Our deep-learning system achieved the area under the receiver operating characteristic curves >0.948 and area under the precision-recall curves >0.866 for the gradability assessment, area under the receiver operating characteristic curves >0.960 and area under the precision-recall curves >0.822 for the measurability assessment, and area under the receiver operating characteristic curves >0.939 and area under the precision-recall curves >0.899 for the DMI assessment across three external validation data sets. Grad-CAM demonstrated the capability of our deep-learning system paying attention to regions related to DMI identification. CONCLUSION: Our proposed multitask deep-learning system might facilitate the development of a simplified assessment of DMI on OCTA images among individuals with diabetes mellitus at high risk for visual loss.

Relationship between Diabetic Retinopathy and Primary Open-Angle Glaucoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Pathophysiological overlaps exist between diabetes and primary open-angle glaucoma (POAG) and presence of diabetes increases the risk of POAG. Considering that diabetic retinopathy (DR) is an ocular complication of diabetes, one could speculate that DR as a severity measure may associate with or even predict POAG. Given that POAG is asymptomatic in early stages, an association to DR may prove clinically important and facilitate an earlier diagnosis of POAG. OBJECTIVES: The aim of the study was to investigate if DR is associated with and predictive of POAG. METHOD: We systematically searched 11 literature databases on May 12, 2021. We screened a total of 1,535 records and found six studies eligible for qualitative and quantitative analysis. Two independent authors reviewed the studies, extracted data, and evaluated risk of bias within individual studies. Studies were reviewed qualitatively, and meta-analyses were made based on the odds ratios (ORs) with 95% confidence intervals (CI) of the association between DR and POAG using the random-effects model. Subgroup analyses were made on the association between subtypes of DR and POAG. RESULTS: Six studies (two longitudinal and four cross-sectional) were eligible for review with a total of 255,614 patients with diabetes, of which 20,483 patients had any degree of DR and 5,258 had POAG. All studies were based on patients with type 2 diabetes except one with both type 1 and type 2 patients. Any DR was not associated with POAG (OR 1.17; 95% CI: 0.58-2.35; p = 0.65). Further stratification revealed that neither cross-sectional (OR 1.00; 95% CI: 0.56-1.81, p = 0.99) nor longitudinal studies (OR 1.47; 95% CI: 0.57-3.78, p = 0.43) demonstrated an association between DR and POAG. CONCLUSIONS: We did not find convincing evidence of an associations between DR and prevalent or incident POAG.

Dexamethasone Intravitreal Implant Is Active at the Molecular Level Eight Weeks after Implantation in Experimental Central Retinal Vein Occlusion.

Central retinal vein occlusion (CRVO) is a visually disabling condition resulting from a thrombus in the major outflow vessel of the eye. The inflammatory response in CRVO is effectively treated with a dexamethasone (DEX) intravitreal implant. Uncovering the proteome changes following DEX implant intervention in CRVO may identify key proteins that mediate the beneficial effects of DEX. In six Göttingen minipigs, CRVO was induced in both eyes with an argon laser using a well-established experimental model. The right eyes were treated with a DEX intravitreal implant (Ozurdex, Allergan), while the left control eyes received a sham injection. Eight weeks after DEX intervention, retinal samples were collected and analyzed with tandem mass tag-based mass spectrometry. DEX implant intervention resulted in the upregulation of peptidyl-prolyl cis-trans isomerase FKBP5 (FKBP5) and ubiquilin-4. Immunohistochemistry showed expression of FKBP5 in the nuclei in all cellular layers of the retina. Cell adhesion molecule 3, tumor necrosis factor receptor superfamily member 16, and trans-1,2-dihydrobenzene-1,2-diol dehydrogenase were downregulated following DEX intervention. The upregulation of the corticosteroid-sensitive protein FKBP5 suggests that the implant remained active at the molecular level after eight weeks of treatment. Future studies may investigate if FKBP5 regulates the efficacy and duration of the DEX implant.

Proteome Analysis of Aflibercept Intervention in Experimental Central Retinal Vein Occlusion.

Aflibercept is a frequently used inhibitor of vascular endothelial growth factor (VEGF) in the treatment of macular edema following central retinal vein occlusion (CRVO). Retinal proteome changes following aflibercept intervention in CRVO remain largely unstudied. Studying proteomic changes of aflibercept intervention may generate a better understanding of mechanisms of action and uncover aspects related to the safety profile. In 10 Danish Landrace pigs, CRVO was induced in both eyes with an argon laser. Right eyes were treated with intravitreal aflibercept while left control eyes received isotonic saline water. Retinal samples were collected 15 days after induced CRVO. Proteomic analysis by tandem mass tag-based mass spectrometry identified a total of 21 proteins that were changed in content following aflibercept intervention. In retinas treated with aflibercept, high levels of aflibercept components were reached, including the VEGF receptor-1 and VEGF receptor-2 domains. Fold changes in the additional proteins ranged between 0.70 and 1.19. Aflibercept intervention resulted in a downregulation of pigment epithelium-derived factor (PEDF) (fold change = 0.84) and endoplasmin (fold change = 0.91). The changes were slight and could thereby not be confirmed with less precise immunohistochemistry and Western blotting. Our data suggest that aflibercept had a narrow mechanism of action in the CRVO model. This may be an important observation in cases when macular edema secondary to CRVO is resistant to aflibercept intervention.

Altered retinal oxygen metabolism in patients with combined ocular and central nervous system sarcoidosis.

OBJECTIVE: To evaluate retinal oxygen metabolism by retinal oximetry for ocular and CNS diseases in a cross-sectional study of sarcoidosis. METHODS: Overall 201 eyes from 103 biopsy-verified sarcoidosis patients were included and divided into four groups depending on the organ affection: (i) sarcoidosis without ocular or CNS affection, (ii) ocular sarcoidosis, (iii) CNS sarcoidosis, and (iv) combined ocular and CNS sarcoidosis. Retinal oximetry was obtained and analysed, with the mean retinal arteriolar and venular saturation as well as arteriovenous difference as principal outcomes. Comparison between groups was done in a multi linear regression model adjusted for age, sex, duration of sarcoidosis, best corrected visual acuity and retinal oximetry quality. RESULTS: Mean (s.d.) age was 50.5 (13.4) (95% CI: 47.9, 53.1) years and 52.2% were males. Eyes of the combined Ocular/CNS group had a higher retinal arteriovenous difference than eyes of the Non-ocular/no-CNS group (42.1% vs 37.7%, P = 0.012) but did not differ between other groups. Eyes in the four groups (Non-ocular/no-CNS, Ocular, CNS and Ocular/CNS) did not differ according to retinal arterial (94.5%, 93.5%, 93.5% and 94.5%, respectively) or venular (57.5%, 56.4%, 55.0% and 52.5%, respectively) oxygen saturation. CONCLUSIONS: The results of this study suggest that eyes of sarcoidosis patients with combined ocular and CNS affection have an altered oxygen metabolism indicating a subclinical eye affection that is not recognized by conventional screening methods.

Retinal Vascular Fractal Dimensions and Their Association with Macrovascular Cardiac Disease.

INTRODUCTION: As the only part of the human vasculature, the retina is available for direct, noninvasive inspection. Retinal vascular fractal dimension (DF) is a method to measure the structure of the retinal vascular tree, with higher noninteger values between 1 and 2 representing a more complex and dense retinal vasculature. Retinal vascular structure has been associated with a variety of systemic diseases, and this study examined the association of DF and macrovascular cardiac disease in a case-control design. METHODS: Retinal fundus photos were captured with Topcon TRC-50X in 38 persons that had coronary artery bypass grafting (CABG, cases) and 37 cardiovascular healthy controls. The semiautomatic software VAMPIRE was used to measure retinal DF. RESULTS: Patients with CABG had lower DF of the retinal main venular vessels compared to the control group (1.15 vs. 1.18, p = 0.01). In a multivariable regression model adjusted for gender and age, eyes in the fourth quartile with higher DF were less likely to have CABG compared to patients in the first (OR, 7.20; 95% confidence interval: 1.63-31.86; p = 0.009) and second (OR, 8.25; 95% confidence interval: 1.70-40.01; p = 0.009) quartiles. CONCLUSIONS: This study demonstrates that lower complexity of main venular vessels associates with higher risk of having CABG. The research supports the hypothesis that the retinal vascular structure can be used to assess nonocular macrovascular disease.

Correlation between Diabetic Retinopathy Severity and Oxygen Metabolism in Patients with Diabetic Macular Edema during Treatment with Intravitreal Aflibercept.

PURPOSE: To attribute data on changes in diabetic retinopathy (DR) severity during treatment of diabetic macular edema (DME) with vascular endothelial growth factor inhibitors (anti-VEGF), this study aimed to (1) examine the correlation between oxygen saturations in retinal vessels and the number of DR lesions on ultra-wide field color fundus photographs prior to anti-VEGF treatment and (2) compare changes in oxygen saturations in retinal vessels with changes in the number of DR lesions after a loading dose of three monthly intravitreal injections of 2.0 mg of aflibercept. METHODS: This 3-month prospective study included 37 eyes of patients with DME and varying severity of peripheral DR lesions. DR lesions were graded on wide field images and retinal oxygen saturations were evaluated by retinal oximetry. Patients were then treated with three monthly intravitreal injections of 2 mg aflibercept and wide field imaging and retinal oximetry were repeated 4 weeks after the last injection. Patients with proliferative DR or previous panretinal photocoagulation were excluded. RESULTS: Baseline retinal arteriolar oxygen saturation increased with increasing DR severity and numbers of microaneurysms, hemorrhages, and cotton wool spots (p = 0.03, 0.01, 0.03, and <0.001), while no correlation between the severity of DR lesions and retinal venular oxygen saturation was found. After treatment with intravitreal aflibercept, the severity of DR lesions significantly reduced, while retinal arteriolar and venular oxygen saturation as well as the arteriolar-venular difference remained unchanged (95.5 vs. 95.8%, p = 0.44; 62.9 vs. 64.5%, p = 0.08; 32.5 vs. 31.4%, p = 0.33). CONCLUSION: This study demonstrated that structural DR lesions correlate with retinal arteriolar oxygen saturation in patients with DME prior to anti-VEGF treatment and that improvement in the severity of DR lesions can occur without corresponding changes in retinal oxygen metabolism during intravitreal therapy. Our results suggest that DR severity on color fundus photographs should be interpreted with caution once intravitreal therapy is initiated.

Long-Term Outcome of Patients Operated with Pars Plana Vitrectomy for Primary Rhegmatogenous Retinal Detachment.

PURPOSE: To determine the long-term outcome of patients operated with pars plana vitrectomy (PPV) for primary rhegmatogenous retinal detachment (RRD) and to identify potential predictors for poor visual outcome. METHODS: Prospective, observational 30-month study of patients operated for primary RRD with PPV. Examinations were performed preoperatively and after months 2, 6, and 30. RESULTS: Eighty-four patients (84 eyes) were included and 73 (86.9%) participated at month 30. The macula was attached in 30 (35.7%) patients at primary operation. The majority of patients (n = 59, 80.8%) achieved a good final best corrected visual acuity (BCVA ≤0.3 logMAR, ≥0.5 Snellen) with a better outcome in patients with the macula attached than detached (0.02 vs. 0.17 logMAR, p = 0.007). Variables associated with poor visual outcome were baseline BCVA >0.3 logMAR (p = 0.03), female gender (p = 0.02), silicone oil (p = 0.03), and larger areas of retinal detachment (p = 0.01). In multivariable regression analysis, female gender (OR = 8.5 [95% CI 1.8-39.8]) was the strongest risk factor for poor visual outcome. CONCLUSION: The majority of patients operated for primary RRD achieved a reasonable long-term visual outcome. Notably, female gender was associated with poor visual outcome, indicating a need for closer follow-up.

Simulation training in vitreoretinal surgery: a systematic review.

BACKGROUND: The purpose of this study was to perform a systematic review of the current literature on simulator-based training in vitreoretinal surgery (VRS). We examined the results regarding simulated VRS and provided an overview of how the current results may be employed in VRS training. Lastly, we evaluated the quality of these results. METHODS: The databases of Pubmed, Embase and Cochrane Library were searched for articles in English involving simulated VRS training. A qualitative analysis was performed, since the studies which met our inclusion criteria did not allow for a quantitative meta-analysis. RESULTS: We identified 203 articles of which seven met the inclusion criteria. Of these, six studies investigated simulation with EyeSi® Surgical (VRMagic, Mannheim, Germany). Six studies reported positive performance curves. Four studies showed construct validity. One study attempted to show skill transfer from simulator to vitrectomies performed on cadavers. Methodological quality of the included studies was moderate but lacking in instrument validation. CONCLUSION: Simulator-based training in VRS can assess and possibly assist acquisition of a variety of VRS skills. Further research is needed to support transfer from simulator to operating room. Future studies should strive to follow established validation frameworks and streamline study designs.

Optical coherence tomography in acute optic neuritis: A population-based study.

OBJECTIVES: To measure early structural damage caused by autoimmune inflammatory optic neuritis (ON) by optical coherence tomography (OCT) in a population-based cohort. METHODS: In a prospective population-based study over 24 months in Southern Denmark, patients diagnosed with acute ON and without prior diagnosis of a chronic neuroinflammatory disorder were included and examined with OCT, visual evoked potentials (VEP), visual fields, high contrast visual acuity (HCVA), and low contrast letter acuity (LCLA). Structural and functional outcomes were determined at 6-month follow-up based on interocular differences. RESULTS: The 50 included patients had on average 16.9 µm peripapillary retinal nerve fiber layer loss, 10.6 µm ganglion cell and inner plexiform layer (GCIP) loss, and an average HCVA decrease of 0.22 dec. Based on a linear regression model, average GCIP loss amounted to -0.2 µm per day and started 8 days after onset. OCT outcomes but not VEP correlated well with all visual function measurements at follow-up. Structural and functional damage in 20 patients (40%) diagnosed de novo with multiple sclerosis (MS) and in 2 patients (4%) with positive myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) test did not differ from patients with idiopathic ON. CONCLUSIONS: Optic neuritis causes substantial retinal damage and vision loss independent of the underlying disease. Our study supports that GCIP damage starts closely to clinical onset. Good structure-function correlations between OCT and vision support the importance of OCT in monitoring acute ON.

Automated Screening for Diabetic Retinopathy - A Systematic Review.

PURPOSE: Worldwide ophthalmologists are challenged by the rapid rise in the prevalence of diabetes. Diabetic retinopathy (DR) is the most common complication in diabetes, and possible consequences range from mild visual impairment to blindness. Repetitive screening for DR is cost-effective, but it is also a costly and strenuous affair. Several studies have examined the application of automated image analysis to solve this problem. Large populations are needed to assess the efficacy of such programs, and a standardized and rigorous methodology is important to give an indication of system performance in actual clinical settings. METHODS: In a systematic review, we aimed to identify studies with methodology and design that are similar or replicate actual screening scenarios. A total of 1,231 publications were identified through PubMed, Cochrane Library, and Embase searches. Three manual search strategies were carried out to identify publications missed in the primary search. Four levels of screening identified 7 studies applicable for inclusion. RESULTS: Seven studies were included. The detection of DR had high sensitivities (87.0-95.2%) but lower specificities (49.6-68.8%). False-negative results were related to mild DR with a low risk of progression within 1 year. Several studies reported missed cases of diabetic macular edema. A meta-analysis was not conducted as studies were not suitable for direct comparison or statistical analysis. CONCLUSION: The study demonstrates that despite limited specificity, automated retinal image analysis may potentially be valuable in different DR screening scenarios with a relatively high sensitivity and a substantial workload reduction.

Structural neurodegeneration correlates with early diabetic retinopathy.

PURPOSE: To examine differences in structural and functional neurodegenerative measurements between patients with no and early diabetic retinopathy (DR). METHODS: In this cross-sectional study, we examined 103 patients with type 2 diabetes mellitus. In 7-field fundus photographs acquired with Topcon TRC-NW6S, a single, certified grader determined the presence of DR according to the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Retinal neurodegeneration was evaluated by Topcon 3D OCT-2000 spectral domain optical coherence tomography (OCT) and by a RETI-scan multifocal electroretinography (mf-ERG) system in rings 1-6. RESULTS: Median age and duration of diabetes were 63.6 and 10 years, respectively, and 46% were men. Median HbA1c was 50 mmol/mol (6.7%), and ETDRS levels were 10 (41.7%, n = 43), 20 (35.0%, n = 36), and 35 (23.3%, n = 24). The duration of diabetes increased with higher levels of DR (p = 0.04), but patients with different level of DR did not differ according to age, sex, blood pressure, HbA1c, and mf-ERG or OCT parameters. In a multiple logistic regression model, macular ganglion cell layer thickness was associated with the presence of DR (OR 1.73 per 5 µm increase, 95% CI 1.06-2.85, p = 0.03). Conversely, retinal nerve fibre layer thickness at optic disc was inversely related to DR (OR 0.69 per 5 µm increase, 95% CI 0.51-0.95, p = 0.02). There were no associations between DR and mf-ERG outcomes. CONCLUSION: In patients with type 2 diabetes, structural neurogenic characteristics were associated with DR. If confirmed by larger prospective studies, these results may indicate that a complex neurovascular interaction is an early event in the pathogenesis of DR.

Ophthalmic epidemiology in Europe: the "European Eye Epidemiology" (E3) consortium.

The European Eye Epidemiology (E3) consortium is a recently formed consortium of 29 groups from 12 European countries. It already comprises 21 population-based studies and 20 other studies (case-control, cases only, randomized trials), providing ophthalmological data on approximately 170,000 European participants. The aim of the consortium is to promote and sustain collaboration and sharing of data and knowledge in the field of ophthalmic epidemiology in Europe, with particular focus on the harmonization of methods for future research, estimation and projection of frequency and impact of visual outcomes in European populations (including temporal trends and European subregions), identification of risk factors and pathways for eye diseases (lifestyle, vascular and metabolic factors, genetics, epigenetics and biomarkers) and development and validation of prediction models for eye diseases. Coordinating these existing data will allow a detailed study of the risk factors and consequences of eye diseases and visual impairment, including study of international geographical variation which is not possible in individual studies. It is expected that collaborative work on these existing data will provide additional knowledge, despite the fact that the risk factors and the methods for collecting them differ somewhat among the participating studies. Most studies also include biobanks of various biological samples, which will enable identification of biomarkers to detect and predict occurrence and progression of eye diseases. This article outlines the rationale of the consortium, its design and presents a summary of the methodology.

Small-incision lenticule extraction (SMILE): outcomes of 722 eyes treated for myopia and myopic astigmatism.

PURPOSE: To study the outcomes of small-incision lenticule extraction (SMILE) for treatment of myopia and myopic astigmatism. METHODS: Retrospective study of patients treated for myopia or myopic astigmatism with SMILE, using a VisuMax(®) femtosecond laser (Carl Zeiss Meditec, Jena, Germany), at the Department of Ophthalmology, Odense University Hospital, Odense, Denmark. Inclusion criteria were corrected distance visual acuity (CDVA) of 20/25 or better before surgery and no ocular conditions other than myopia up to -10.00 diopters (D) with astigmatism up to 3.00 D. RESULTS: Of the 729 treatments, 722 were included. The spherical equivalent (SE) refraction averaged -6.82 ± 1.66 diopters (D) before surgery. After 3 months, 88 % of eyes were within ±0.50 D of the intended refraction, whilst 98 % were within ±1.00 D. The mean difference between attempted and achieved SE refraction at 3 months after surgery was -0.06 ± 0.01 D (range: -1.25 to 1.25 D). In eyes with emmetropia as target refraction (n = 362), 63 % had uncorrected distance visual acuity (UDVA) of 20/25 or better 1 day after surgery, rising to 83 % at 3 months after surgery. The average gain in CDVA from before surgery to 3 months after surgery was 0.07 ± 0.03 (logMAR). However, 12 eyes (1.6 %) lost 2 or more lines of CDVA from before surgery to 3 months postoperatively. Simultaneous treatment of up to 3.00 D of astigmatism was not associated with less predictable refractive outcomes. CONCLUSIONS: In the short term, SMILE seemed predictable, efficient, and safe for treatment of myopia and myopic astigmatism.

Vascular Changes and Neurodegeneration in the Early Stages of Diabetic Retinopathy: Which Comes First?

INTRODUCTION: Neurodegeneration is an early component of diabetic retinopathy (DR). It is unclear whether neurodegeneration is an independent factor or a consequence of damaged retinal vasculature. The aims of this study were to review the literature concerning neurodegeneration in diabetic patients without or with early DR, and to examine whether neurodegeneration precedes visible vasculopathy in the pathogenesis of DR. METHODS: A systematic literature search was performed to identify studies which used optical coherence tomography (OCT) or multifocal electroretinography (mfERG) to detect neurodegeneration in patients with no or mild DR as compared to healthy controls. Outcome measures were mean retinal thickness (RT), mean retinal nerve fiber layer (RNFL) thickness and ganglion cell layer (GCL) thickness. Also, mfERG amplitude and implicit time were analyzed. RESULTS: Eleven studies which used mfERG and/or OCT to detect neurodegeneration were included. Two OCT studies found significant thinning of RT, 2 found thinning of RNFL, whereas 1 found thickening of RT, RNFL and GCL in patients without DR. Two mfERG studies found a significant delay of implicit time in the same patient group. Retinal thinning and delay of implicit time were also detected in patients with mild DR. CONCLUSION: Retinal neurodegeneration is an early component of DR, which can precede visible vasculopathy.

Correlation between Retinal Vessel Calibre and Neurodegeneration in Patients with Type 2 Diabetes Mellitus in the European Consortium for the Early Treatment of Diabetic Retinopathy (EUROCONDOR).

PURPOSE: To investigate the correlation between retinal vessel calibre and measurements of neurodegeneration in patients with type 2 diabetes (T2D) and no or early diabetic retinopathy (DR). METHODS: Baseline data on 440 patients with T2D from the EUROCONDOR clinical trial were used. DR was graded according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) scale, and patients with ETDRS levels 10-35 were included. Retinal vessel diameters were measured by semi-automatic software. Calibres were summarized into central retinal artery and vein equivalents (CRAE and CRVE). RESULTS: Median age and diabetes duration were 64.0 and 10.3 years, respectively. ETDRS levels were 10 (42.3%), 20 (27.5%) and 35 (30.2%). The median CRAE and CRVE were 146.7 and 215.3 µm, respectively. CRAE did not differ according to ETRDS level (p = 0.12), but wider CRVE were found in patients with higher ETDRS levels (p = 0.04). In a multivariable linear regression model, CRAE was associated with macular ganglion cell layer thickness (coefficient 0.27 per micrometre, p < 0.01), and CRVE was correlated with macular retinal thickness (coefficient -0.07 per micrometre, p = 0.04) and retinal nerve fibre layer thickness at the optic disc (coefficient 0.32 per micrometre, p < 0.01). CONCLUSION: Retinal vessel calibre was independently associated with structural changes of the neuroretina in patients with no or early DR.

Four-year to seven-year outcomes of advanced surface ablation with excimer laser for high myopia.

PURPOSE: We aimed to evaluate and compare outcomes after photorefractive keratectomy with cooling (cPRK) and laser-assisted subepithelial keratectomy (LASEK) for high myopia. METHODS: This was a retrospective, single-masked follow-up study of patients treated for myopia between 2007 and 2009 with cPRK or LASEK, using a high-frequency flying-spot excimer laser with eye-tracker (MEL80; Carl Zeiss, Jena, Germany). One eye of each patient was randomly chosen for analysis. Re-treated eyes were excluded. RESULTS: Forty-six cPRK patients and 35 LASEK patients were included. Spherical equivalent averaged -7.69 ± 1.47 diopters (D) in cPRK eyes and -7.98 ± 2.06 D in LASEK eyes (p = 0.31) before surgery. The average follow-up time was 4.6 years in cPRK patients and 6.0 years in LASEK patients (p < 0.05). At final follow-up, no cPRK eyes and one LASEK eye (p = 0.46) had lost two lines of corrected distance visual acuity (CDVA). No eyes had significant haze at final follow-up, although trace haze was found in four cPRK eyes and six LASEK eyes (p = 0.44). However, at 6 weeks after surgery, zero cPRK eyes and nine LASEK eyes (p < 0.05) had significant haze. At final follow-up, 63 % of cPRK eyes and 35 % of LASEK eyes (p = 0.17) were within ±1.0 D of intended refraction. Finally, 100 % of cPRK patients and 92 % of LASEK patients (p = 0.87) were satisfied or very satisfied with the surgery at final follow-up. CONCLUSION: cPRK and LASEK seemed safe and with high patient satisfaction 4 to 7 years after surgery for high myopia. However, cPRK was more effective than LASEK in reducing initial significant corneal haze.