Alcohol consumption and microvascular dysfunction: a J-shaped association: The Maastricht Study.

BACKGROUND: Microvascular dysfunction (MVD) is an important contributor to major clinical disease such as stroke, dementia, depression, retinopathy, and chronic kidney disease. Alcohol consumption may be a determinant of MVD. OBJECTIVE: Main objectives were (1) to study whether alcohol consumption was associated with MVD as assessed in the brain, retina, skin, kidney and in the blood; and (2) to investigate whether associations differed by history of cardiovascular disease or sex. DESIGN: We used cross-sectional data from The Maastricht Study (N = 3,120 participants, 50.9% men, mean age 60 years, and 27.5% with type 2 diabetes [the latter oversampled by design]). We used regression analyses to study the association between total alcohol (per unit and in the categories, i.e. none, light, moderate, high) and MVD, where all measures of MVD were combined into a total MVD composite score (expressed in SD). We adjusted all associations for potential confounders; and tested for interaction by sex, and history of cardiovascular disease. Additionally we tested for interaction with glucose metabolism status. RESULTS: The association between total alcohol consumption and MVD was non-linear, i.e. J-shaped. Moderate versus light total alcohol consumption was significantly associated with less MVD, after full adjustment (beta [95% confidence interval], -0.10 [-0.19; -0.01]). The shape of the curve differed with sex (Pinteraction = 0.03), history of cardiovascular disease (Pinteraction < 0.001), and glucose metabolism status (Pinteraction = 0.02). CONCLUSIONS: The present cross-sectional, population-based study found evidence that alcohol consumption may have an effect on MVD. Hence, although increasing alcohol consumption cannot be recommended as a policy, this study suggests that prevention of MVD may be possible through dietary interventions.

Carotid stiffness is associated with retinal microvascular dysfunction-The Maastricht study.

OBJECTIVE: This study investigated whether arterial stiffening is a determinant of subtle retinal microvascular changes that precede diabetic retinopathy. RESEARCH DESIGN AND METHODS: This study used cross-sectional data from the Maastricht Study, a type 2 diabetes-enriched population-based cohort study. We used multivariable linear regression analysis to investigate, in individuals without and with type 2 diabetes, the associations of carotid distensibility coefficient and carotid-femoral pulse wave velocity with retinal microvascular diameters and flicker light-induced dilation and adjusted for cardiovascular and lifestyle risk factors. RESULTS: The retinal microvascular diameter study population consisted of N = 2434 participants (51.4% men, mean ± SD age 59.8 ± 8.1 years, and 28.1% type 2 diabetes). No measures of arterial stiffness were significantly associated with microvascular diameters. Greater carotid distensibility coefficient (i.e., lower carotid stiffness) was significantly associated with greater retinal arteriolar flicker light-induced dilation (per standard deviation, standardized beta [95% CI] 0.06 [0.00; 0.12]) and non-significantly, but directionally similarly, associated with greater retinal venular flicker light-induced dilation (0.04 [-0.02; 0.10]). Carotid-femoral pulse wave velocity (i.e., aortic stiffness) was not associated with retinal microvascular flicker light-induced dilation. The associations between carotid distensibility coefficient and retinal arteriolar and venular flicker light-induced dilation were two- to threefold stronger in individuals with type 2 diabetes than in those without. CONCLUSION: In this population-based study greater carotid, but not aortic, stiffness was associated with worse retinal flicker light-induced dilation and this association was stronger in individuals with type 2 diabetes. Hence, carotid stiffness may be a determinant of retinal microvascular dysfunction.

A systematic approach to evaluate practice-based process- and outcome data applied to the treatment of neovascular age-related macular degeneration.

BACKGROUND: Following the principles of value-based health care, outcomes and processes of daily-practice eye care need to be systematically evaluated. We illustrate an approach that can be used to support data-driven quality improvements. We used patient data regarding the treatment of neovascular age-related macular degeneration (nAMD). METHODS: In a cohort study, we reviewed medical records of patients with nAMD confirmed on fluorescein angiography (FA). Patients were treated with intravitreal injections with bevacizumab; ranibizumab; or photodynamic therapy (PDT). Visual acuity (VA), ophthalmic exam results and treatments were recorded. VA was compared between treatments by linear mixed model. Diagnosis was re-evaluated on the original FAs. Outcome analysis was performed by 1) selecting VA as the relevant outcome parameter; 2) Preventing selection by comparing treatments with historical untreated cohort and cohorts from the literature, 3) correcting for confounding due to lesion type, and 4) identifying relevant process variables that affect the outcome. These were severity of disease at presentation, and doctor- and patient dependent process variables. RESULTS: In total, 473 eyes were included. At 12 months, change in VA was 0.54, 0.48, 0.09, and 0.07 LogMAR in the no-treatment, photodynamic therapy (PDT), bevacizumab, and ranibizumab groups, respectively. Lesion type on FA differed between groups. Diagnosis of nAMD could not be confirmed in 104 patients. Patient delay, inaccurate diagnosis and treatment intervals may have impacted outcomes. CONCLUSIONS: The effect of PDT was small to absent. Anti-VEGFs were effective and appeared as effective as in RCTs. Correct selection of a comparator cohort and addressing confounding, including confounding by indication and effect modification, are needed to achieve valid results and interpretation. Patient delay, diagnosis accuracy, indication for and application of treatment can potentially be improved to improve treatment outcomes. In a value-based care perspective, systematic evaluation of diagnostic accuracy, treatment indication, protocols, and outcomes of new interventions is needed at an early stage to improve outcomes.

Prevention of macular edema after cataract surgery.

PURPOSE OF REVIEW: Although cataract surgery can effectively restore visual function in many patients with cataract, PCME remains an important cause of suboptimal visual acuity. The present review provides an overview of the current literature on the prevention and treatment of PCME. RECENT FINDINGS: Optimal prevention of PCME starts preoperatively with a personalized risk assessment. Diabetes mellitus, retinal vein occlusion, epiretinal membrane, macular hole, and uveitis are the most important risk factors for developing cystoid macular edema after cataract surgery. Topical NSAIDs either in addition to, or instead of, topical corticosteroids reduce the risk of developing PCME. Additional intravitreal corticosteroid and antivascular endothelial growth factor injections have been studied in patients with diabetes. Timely diagnosis and treatment of PCME is essential. Topical NSAIDs solely, or in addition to corticosteroids, improve visual acuity in patients with PCME. Oral acetazolamide and intravitreal dexamethasone implants have been used in refractory cases. SUMMARY: Topical NSAIDs can be used solely, or in combination with topical corticosteroids, to prevent and treat PCME. Further research is needed to compare the efficacy of various NSAIDs, and to investigate the cost-effectiveness and long-term benefit of anti-inflammatory treatments on visual acuity, contrast sensitivity, and quality of life.

Prediabetes and Type 2 Diabetes Are Associated With Generalized Microvascular Dysfunction: The Maastricht Study.

BACKGROUND: Type 2 diabetes (T2DM) is associated with an increased risk of cardiovascular disease. This can be partly explained by large-artery dysfunction, which already occurs in prediabetes ("ticking clock hypothesis"). Whether a similar phenomenon also applies to microvascular dysfunction is not known. We therefore tested the hypothesis that microvascular dysfunction is already present in prediabetes and is more severe in T2DM. To do so, we investigated the associations of prediabetes, T2DM, and measures of hyperglycemia with microvascular function measured as flicker light-induced retinal arteriolar dilation and heat-induced skin hyperemia. METHODS: In the Maastricht Study, a T2DM-enriched population-based cohort study (n=2213, 51% men, aged [mean±standard deviation] 59.7±8.2 years), we determined flicker light-induced retinal arteriolar %-dilation (Dynamic Vessel Analyzer), heat-induced skin %-hyperemia (laser-Doppler flowmetry), and glucose metabolism status (oral glucose tolerance test; normal glucose metabolism [n=1269], prediabetes [n=335], or T2DM [n=609]). Differences were assessed with multivariable regression analyses adjusted for age, sex, body mass index, smoking, physical activity, systolic blood pressure, lipid profile, retinopathy, estimated glomerular filtration rate, (micro)albuminuria, the use of lipid-modifying and blood pressure-lowering medication, and prior cardiovascular disease. RESULTS: Retinal arteriolar %-dilation was (mean±standard deviation) 3.4±2.8 in normal glucose metabolism, 3.0±2.7 in prediabetes, and 2.3±2.6 in T2DM. Adjusted analyses showed a lower arteriolar %-dilation in prediabetes (B=-0.20, 95% confidence interval -0.56 to 0.15) with further deterioration in T2DM (B=-0.61 [-0.97 to -0.25]) versus normal glucose metabolism (P for trend=0.001). Skin %-hyperemia was (mean±standard deviation) 1235±810 in normal glucose metabolism, 1109±748 in prediabetes, and 937±683 in T2DM. Adjusted analyses showed a lower %-hyperemia in prediabetes (B=-46 [-163 to 72]) with further deterioration in T2DM (B=-184 [-297 to -71]) versus normal glucose metabolism (P for trend=0.001). In addition, higher glycohemoglobin A1c and fasting plasma glucose were associated with lower retinal arteriolar %-dilation and skin %-hyperemia in fully adjusted models (for glycohemoglobin A1c, standardized B=-0.10 [-0.15 to -0.05], P<0.001 and standardized B=-0.13 [-0.19 to -0.07], P<0.001, respectively; for fasting plasma glucose, standardized B=-0.09 [-0.15 to -0.04], P<0.001 and standardized B=-0.10 [-0.15 to -0.04], P=0.002, respectively). CONCLUSION: Prediabetes, T2DM, and measures of hyperglycemia are independently associated with impaired microvascular function in the retina and skin. These findings support the concept that microvascular dysfunction precedes and thus may contribute to T2DM-associated cardiovascular disease and other complications, which may in part have a microvascular origin such as impaired cognition and heart failure.

Tracing the natural course of visual acuity and quality of life in neovascular age-related macular degeneration: a systematic review and quality of life study.

BACKGROUND: Describing the natural course of neovascular age-related macular degeneration (nAMD) is essential in discussing prognosis and treatment options with patients and to support cost-effectiveness studies. METHODS: First, we performed a literature search in PubMed, Embase, and Cochrane. We included randomized clinical trials and prospective observational studies reporting visual acuity (VA) in non-treated patients, 24 studies in total. We integrated VA data using best fit on Lineweaver-Burke plots and modelled with non-linear regression using reciprocal terms. Second, we performed a quality-of-life (QoL) study in nAMD patients. We measured VA with Radner reading charts and QoL with the Health Utilities Index issue 3 (HUI-3) questionnaire in 184 participants. We studied the relation VA-QoL with linear regression. Third, with Monte Carlo simulation, we integrated the VA model from the literature review and the relation VA-QoL from the QoL study. RESULTS: Visual acuity was 0.4 and 0.07 after 5 years in the better-seeing, and worse-seeing eye, respectively. After 4.3 years, VA was <0.5 in the better-seeing eye; <0.3 after 7 years; 0.05 after 17 years. QoL score decreased from 0.6 to 0.45 after 10 years. CONCLUSIONS: The natural course of nAMD in both eyes needs to be considered when informing patients. Visual acuity in the best eye decreases to below 0.5 in 4.3 years. This affects QoL significantly.

Distinguishing between Better and Worse Visual Acuity by Studying the Correlation with Quality of Life in Neovascular Age-Related Macular Degeneration.

PURPOSE: To determine whether there is a level of visual acuity (VA) in neovascular age-related macular degeneration (nAMD) above which the correlation of VA with disease-related quality of life (QoL) is significantly greater than below this level. DESIGN: An observational, cross-sectional study. PARTICIPANTS: A total of 184 patients with nAMD aged at least 50 years were included in the study. METHODS: In face-to-face interviews, we assessed QoL with the Macular Disease-Dependent Quality of Life (MacDQoL) questionnaire. We measured VA with standardized Radner reading charts. We used regression splines analysis with a single hinge point, with the MacDQoL score as the dependent variable and VA as the independent variable. The x-coordinate (VA) of the hinge point was varied and tested with each iteration. A second method of regression splines analysis was also performed, without a preset hinge point. MAIN OUTCOME MEASURES: The primary outcome measure is the cutoff point at or below which VA is associated with significantly less change in QoL than above this cutoff. The linear coefficients below and above the cutoff are defined as change in MacDQoL score per logarithm of the minimum angle of resolution (logMAR) unit of change in VA. RESULTS: With Snellen equivalent VA 0.05 (1.3 logMAR) or worse, the linear coefficient was 0.15. With VA better than 0.05, the linear coefficient was 2.40 (P value of the difference: 0.009). CONCLUSIONS: When VA is above 0.05, there is a stronger and significant relation between VA and QoL. At or below this level, the relation between VA and QoL approaches zero. With better VA, a difference in VA implies a significant difference in QoL. With poorer VA, a difference in VA is unlikely to imply a difference in QoL. Therefore, in treating nAMD, the aim should be to keep Snellen VA above 0.05 to have an impact on QoL. If it is certain that the best-corrected VA below 0.05 is permanent, these findings imply there may be less, if any, benefit to continue further treatment. This is to be evaluated on a case-by-case basis.

The cost-utility of aflibercept for the treatment of age-related macular degeneration compared to bevacizumab and ranibizumab and the influence of model parameters.

BACKGROUND: Age-related macular degeneration (AMD) is a blinding disease placing considerable burden on society due to blindness-associated costs. Intravitreal anti-vascular endothelial growth factors (anti-VEGFs) are effective in reducing the incidence of blindness, but at potentially high costs, depending on the cost of the drug used. Aflibercept has been introduced as an anti-VEGF equally effective to ranibizumab, but less costly. For this new drug, new cost-effectiveness analyses are needed, and AMD models used today give biased results. We investigated the cost-effectiveness of aflibercept compared to bevacizumab, ranibizumab, and no treatment and studied the influence of commonly used model parameters. METHODS: A patient-level, visual acuity-based, 2-eye model was developed. Data on effectiveness were derived from randomized controlled trials evaluating the outcomes of aflibercept, bevacizumab, and ranibizumab. Utility and resource utilization were assessed in interviews with AMD patients. Costs were based on standard health care cost prices. Time horizons were two and five years. A societal perspective was employed. RESULTS: Over five years, costs associated with aflibercept treatment were 36,030, with 2.15 QALYs. Costs associated with the bevacizumab regimens, ABC study as-needed (PRN); CATT study PRN; and CATT study 1×/month, were 19,367; 26,746; and 30,520, with 2.16; 2.17; and 2.15 QALYs, respectively. Costs associated with ranibizumab PRN and 1×/month were 45,491 and 74,837 with 2.16 and 2.15 QALYs, respectively. 'No treatment' was associated with 9530 and 1.96 QALYs. The incremental cost-effectiveness ratios versus 'no treatment' were: aflibercept-140,274; bevacizumab-51,062 (ABC PRN), 83,256 (CATT PRN) and 110,361 (1×/month); ranibizumab-181,667 (PRN) and 349,773 (1×/month). Results were highly dependent on whether only one or both eyes were included, length of time horizon, and whether the costs of blindness and low-vision were included in the analysis. CONCLUSIONS: Aflibercept is a cost-effective treatment for AMD over ranibizumab. However, aflibercept is not a cost-effective treatment when compared to bevacizumab. Application of inappropriate model assumptions leads to a biased cost-saving estimate of the cost-effectiveness of aflibercept. Therefore, cost-effectiveness analyses should be conducted with appropriate models.

An evidence-based review of prognostic factors for glaucomatous visual field progression.

PURPOSE: To examine which prognostic factors are associated with glaucomatous visual field progression. DESIGN: Knowledge of prognostic factors helps clinicians to select patients at risk of glaucomatous visual field progression and intensify their treatment. METHODS: By consulting relevant databases, we identified 2733 articles published up to September 2010, of which 85 articles investigating prognostic factors for visual field progression in patients with open-angle glaucoma (OAG) were eligible. We summarized results for each factor in tables, noting the direction of the association between the prognostic factor and progression, and the accompanying P value. Four authors, working blind to the factors, independently judged the extent to which a prognostic factor was associated with glaucomatous visual field progression. If there were different associations for normal-tension glaucoma (NTG) studies, they were judged separately. Consensus was reached during group meetings. MAIN OUTCOME MEASURES: A ranking of all studied prognostic factors for glaucomatous visual field progression according to their likelihood of being prognostic. RESULTS: A total of 103 different prognostic factors were investigated in 85 articles. The following factors were clearly associated with glaucomatous visual field progression: age, disc hemorrhages (for NTG), baseline visual field loss, baseline intraocular pressure (IOP), and exfoliation syndrome. An association was unlikely for family history of glaucoma, atherosclerosis, systemic hypertension, visual acuity, sex (for NTG), systolic blood pressure, myopic refractive error (for NTG), and Raynaud's phenomenon. CONCLUSIONS: The factors we found clearly associated with progression could be used in clinical practice and for developing clinical prediction models. For many other factors, further research is necessary.

Retinal Functional and Structural Neural Indices: Potential Biomarkers for the Monitoring of Cerebral Neurodegeneration: The Maastricht Study.

BACKGROUND: If retinal indices of neurodegeneration are to be biomarkers for the monitoring of cerebral neurodegeneration, it is important to establish whether potentially modifiable risk factors for dementia are associated with retinal neurodegenerative changes. OBJECTIVE: To study associations of dementia risk factors with retinal sensitivity, an index of retinal neural function, and retinal nerve fiber layer (RNFL) thickness, an index of retinal neural structure. METHODS: We used cross-sectional data from The Maastricht Study (up to 5,666 participants, 50.5% men, mean age 59.7), and investigated associations with regression analyses (adjusted for potential confounders). RESULTS: Most risk factors under study (i.e., hyperglycemia, unhealthy diet, lower cardiorespiratory fitness, smoking, alcohol consumption, and hypertension) were significantly associated with lower retinal sensitivity and lower RNFL thickness. CONCLUSION: Findings of this population-based study support the concept that retinal neural indices may be biomarkers for the monitoring of therapeutic strategies that aim to prevent early-stage cerebral neurodegeneration and, ultimately, dementia.

Usefulness and acceptability of a standardised orientation and mobility training for partially-sighted older adults using an identification cane.

BACKGROUND: Orientation and mobility (O&M) training in using an identification (ID) cane is provided to partially-sighted older adults to facilitate independent functioning and participation in the community. Recently, a protocolised standardised O&M-training in the use of the ID cane was developed in The Netherlands. The purpose of this study is to assess the usefulness and acceptability of both the standardised training and the regular training for participants and O&M-trainers in a randomised controlled trial (NCT00946062). METHODS: The standardised O&M-training consists of two structured face-to-face sessions and one telephone follow-up, in which, in addition to the regular training, self-management and behavioural change techniques are applied. Questionnaires and interviews were used to collect data on the training's usefulness, e.g. the population reached, self-reported benefits or achievements, and acceptability, e.g. the performance of the intervention according to protocol and participants' exposure to and engagement in the training. RESULTS: Data was collected from 29 O&M-trainers and 68 participants. Regarding the self-reported benefits, outcomes were comparable for the standardised training and the regular training according the trainers and participants e.g., about 85% of the participants in both groups experienced benefits of the cane and about 70% gained confidence in their capabilities. Participants were actively involved in the standardised training. Nearly 40% of the participants in the standardised training group was not exposed to the training according to protocol regarding the number of sessions scheduled and several intervention elements, such as action planning and contracting. CONCLUSIONS: The standardised and regular O&M-training showed to be useful and mostly acceptable for the partially-sighted older adults and trainers. Yet, a concern is the deviation from the protocol of the standardised O&M-training by the O&M-trainers regarding distinguishing elements such as action planning. Overall, participants appreciated both trainings and reported benefit.

Effect of combined water drinking test and dark room provocative testing in Caucasian eyes with narrow angles.

PURPOSE: To assess the usefulness of water drinking test and dark room provocative testing (WDT + DRPT) in current clinical practice by evaluating input parameters from Swept-source Optical Coherence Tomography (SS-OCT) images, and to determine if clinical factors like axial length, central endothelial cell count (CECC) and retinal nerve fibre layer thickness (RNFL) thickness are associated with a positive WDT + DRPT. METHODS: SS-OCT examination was performed in consecutive subjects presenting as new patients in the outpatient clinic aged > 40 years. If at least one eye met the inclusion criteria (anterior chamber angles <20° and anterior chamber depth < 2.5 mm on SS-OCT), subjects were included in this study and WDT + DRPT was carried out. The eye with the smallest angle was analysed. The difference in parameters between eyes with a positive (≥8 mmHg) and negative (<8 mmHg) increase in intraocular pressure (IOP) after WDT + DRPT were statistically analysed. Second, the correlation between IOP increase after WDT + DRPT and anterior chamber angle parameters (RNFL thickness, CECC and axial length) was studied. RESULTS: A total of 95 subjects with a mean age of 64 years were included. There was an association between IOP increase after WDT + DRPT and anterior chamber angle characteristics, however this was not of clinical significance. No positive results after WDT + DRPT were found in patients with anterior chamber angles ≥ 20°. CONCLUSIONS: The present findings indicate that this combined provocative test has no definite correlative or predictive value in angle closure disease. Further, the test is not useful in predicting early diagnosis or possible CECC or RNFL loss.

Economic evaluation of prevention of cystoid macular edema after cataract surgery in diabetic patients: ESCRS PREMED study report 6.

PURPOSE: To investigate the cost-effectiveness of prophylactic treatments against cystoid macular edema after cataract surgery in diabetic patients. SETTING: 7 ophthalmology clinics in the Netherlands and Belgium. DESIGN: Prospective trial-based cost-effectiveness analysis using data from a European multicenter randomized clinical trial. METHODS: Diabetic patients (n = 163) undergoing uneventful cataract surgery were randomized to perioperative subconjunctival triamcinolone acetonide (n = 36), perioperative intravitreal bevacizumab (n = 36), combination treatment (n = 45), or no additional treatment (control group, n = 46). The cost analysis was performed from a healthcare perspective within a 12-week postoperative time horizon. The main effectiveness outcome was quality-adjusted life years (QALYs). The main cost-effectiveness outcome was the incremental cost-effectiveness ratio (ICER; cost per QALY). RESULTS: The mean total healthcare costs and QALYs were as follows: triamcinolone group €1827 (U.S. dollars [$] 2295)/0.166; bevacizumab group €2050 ($2575)/0.144; combination group €2027 ($2546)/0.166; and control group €2041 ($2564)/0.156. Bevacizumab and control treatment were most costly and least effective. The ICER was €321 984 ($404 503) per QALY for the combination group compared with that of the triamcinolone group. Assuming the willingness-to-pay as €20 000 ($25 126) per QALY, the cost-effectiveness probability was 70% and 23% in the triamcinolone and combination groups, respectively. No patient who received triamcinolone developed clinically significant macular edema (CSME). A secondary cost-effectiveness analysis based on this outcome showed a clear preference for triamcinolone. CONCLUSIONS: In diabetic patients, subconjunctival triamcinolone was effective in preventing CSME after cataract surgery. The cost-effectiveness analysis showed that triamcinolone is also cost-effective.

(Pre)diabetes, glycemia, and daily glucose variability are associated with retinal nerve fiber layer thickness in The Maastricht Study.

Retinopathy and neuropathy in type 2 diabetes are preceded by retinal nerve fibre layer (RNFL) thinning, an index of neurodegeneration. We investigated whether glucose metabolism status (GMS), measures of glycaemia, and daily glucose variability (GV) are associated with RNFL thickness over the entire range of glucose tolerance. We used cross-sectional data from The Maastricht Study (up to 5455 participants, 48.9% men, mean age 59.5 years and 22.7% with type 2 diabetes) to investigate the associations of GMS, measures of glycaemia (fasting plasma glucose [FPG], 2-h post-load glucose [2-h PG], HbA1c, advanced glycation endproducts [AGEs] assessed as skin autofluorescence [SAF]) and indices of daily GV (incremental glucose peak [IGP] and continuous glucose monitoring [CGM]-assessed standard deviation [SD]) with mean RNFL thickness. We used linear regression analyses and, for GMS, P for trend analyses. We adjusted associations for demographic, cardiovascular risk and lifestyle factors, and, only for measures of GV, for indices of mean glycaemia. After full adjustment, type 2 diabetes and prediabetes (versus normal glucose metabolism) were associated with lower RNFL thickness (standardized beta [95% CI], respectively - 0.16 [- 0.25; - 0.08]; - 0.05 [- 0.13; 0.03]; Ptrend = 0.001). Greater FPG, 2-h PG, HbA1c, SAF, IGP, but not CGM-assessed SD, were also associated with lower RNFL thickness (per SD, respectively - 0.05 [- 0.08; - 0.01]; - 0.06 [- 0.09; - 0.02]; - 0.05 [- 0.08; - 0.02]; - 0.04 [- 0.07; - 0.01]; - 0.06 [- 0.12; - 0.01]; and - 0.07 [- 0.21; 0.07]). In this population-based study, a more adverse GMS and, over the entire range of glucose tolerance, greater glycaemia and daily GV were associated with lower RNFL thickness. Hence, early identification of individuals with hyperglycaemia, early glucose-lowering treatment, and early monitoring of daily GV may contribute to the prevention of RNFL thinning, an index of neurodegeneration and precursor of retinopathy and neuropathy.

Endothelial cell loss and visual outcome of deep anterior lamellar keratoplasty versus penetrating keratoplasty: a randomized multicenter clinical trial.

OBJECTIVE: To compare endothelial cell (EC) loss, visual and refractive outcomes, and complications after deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PK). DESIGN: Randomized, multicenter clinical trial. PARTICIPANTS: Fifty-six eyes of 56 patients with a corneal stromal pathology not affecting the endothelium were randomized to DALK or PK. METHODS: The DALK procedure was performed according to Anwar's big-bubble technique. Patients underwent an ophthalmic examination preoperatively and 3, 6, and 12 months postoperatively. MAIN OUTCOME MEASURES: Endothelial cell loss, refractive and topographic astigmatism, spherical equivalent, uncorrected visual acuity, and best spectacle-corrected visual acuity (BSCVA) were measured, and complications were recorded. RESULTS: Endothelial cell loss was significantly higher after PK compared with DALK procedures performed without perforation of Descemet's membrane (12 months: 27.7% ± 11.1% vs. 12.9% ± 17.6%). The BSCVA was significantly better in the PK group at 3 and 6 months after surgery but was not significantly different 12 months after surgery (0.39 ± 0.3 logarithm of the minimum angle of resolution [logMAR] in DALK and 0.31 ± 0.3 logMAR in PK). At 12 months postoperatively, refractive and topographic astigmatism in the DALK and PK groups were -3.37 ± 2.3 diopters (D) and -3.76 ± 2.1 D (P = 0.53), and 3.57 ± 2.3 D and 4.16 ± 2.0 D (P = 0.34), respectively. (Micro)perforation of the Descemet's membrane occurred in 32% (9/28) of the DALK eyes, and 18% (5/28) of the patients required conversion to PK. Endothelial cell loss was not significantly different between DALK and PK when cases with perforation of Descemet's membrane were included in the (intention-to-treat) analysis (12 months: 19.1 ± 21.6 vs. 27.7 ± 11.1 P = 0.112). Rejection episodes were reported in 1 patient in the DALK group (epithelial rejection) and 3 patients in the PK group (all endothelial rejections). No graft failure occurred. CONCLUSIONS: One year after DALK performed without perforation of Descemet's membrane, EC loss is significantly lower, whereas the BSCVA is comparable to that in the PK group. In addition, no endothelial rejection occurred in the DALK group. However, Descemet's membrane perforation remains a major complication in DALK and warrants improvements to standardize the big-bubble technique.

A systematic review of the adverse events of intravitreal anti-vascular endothelial growth factor injections.

BACKGROUND: Intravitreal ranibizumab and pegaptanib are registered for neovascular age-related macular degeneration. No formal safety study has been conducted for intravitreal bevacizumab. These anti-vascular endothelial growth factor (anti-VEGF) drugs are being used on a large scale in daily practice for different ocular diseases. The objective of the present study was to systematically assess and compare the incidences of adverse events of anti-VEGFs. METHODS: A systematic search was conducted in April 2009 with no date restrictions in PubMed, Embase, Toxline, and the Cochrane library. We used the terms pegaptanib, bevacizumab, ranibizumab, intravitreal, and specific and general terms for adverse events. Studies describing adverse events after anti-VEGF injections and the official safety data were included. RESULTS: Two hundred and seventy-eight articles were included, and the incidences of adverse events were calculated separately for effect, safety, and specific side effect studies. The incidences of serious ocular and nonocular adverse events were approximately below 1 per 100 injections for intravitreal bevacizumab, intravitreal ranibizumab, and intravitreal pegaptanib. Most mild ocular adverse events were below 5 per 100 injections. CONCLUSION: The reported rates of serious adverse events were low after anti-VEGF injections. There is no sufficient evidence to conclude that there is a difference in incidences between the anti-VEGFs.

Contributing ocular comorbidity to end-of-life visual acuity in medically treated glaucoma patients, ocular hypertension and glaucoma suspect patients.

AIM: To assess the visual acuity at the end of life in glaucoma suspect patients, ocular hypertension, and patients treated for glaucoma and to find factors contributing to a reduced visual acuity in this cohort of deceased patients. METHODS: In a cohort of 3883 medically treated glaucoma patients, glaucoma suspect, or patients with ocular hypertension assembled in 2001-2004, 1639 were deceased. Patient data were collected from electronic and paper patient files. The files of 1378 patients were studied and the last measured visual acuity and ocular comorbidities influencing the visual acuity were extracted. RESULTS: Our results show that only 37.2% of patients had no visual impairment in either eye, 30.5% was visually impaired or blind in both eyes and 4.1% was blind in both eyes, all based on VA. The most common contributing factors for severe visual impairment or blindness (prevalence ≥ 1%) were: glaucoma, retinal vein occlusion, dry and exudative age-related macular degeneration, past retinal detachment, amblyopia, diabetic retinopathy, anterior ischemic optic neuropathy, trauma, decompensated cornea, past keratitis, enucleation, corneal transplantation, and macular hole. CONCLUSIONS: Despite the current advanced treatment modalities for glaucoma, 30.5% of patients had a VA < 0.5 in both eyes and 4.1% was blind in both eyes. However, this disability cannot be confidently attributed only to glaucoma. Besides glaucoma, most common contributing factors were among others retinal and macular diseases. Patient management in glaucoma should be based on more than lowering the intraocular pressure to prevent blindness at the end of life.

Economic evaluation of prevention of cystoid macular edema after cataract surgery in patients without diabetes: ESCRS PREMED study report 4.

PURPOSE: To investigate the cost-effectiveness of prophylactic treatments against cystoid macular edema (CME) after cataract surgery in patients without diabetes. SETTING: Seven ophthalmology clinics in the Netherlands and Belgium. DESIGN: Prospective cost-effectiveness analysis using data from a European multicenter randomized clinical trial (ESCRS PREMED). METHODS: Patients without diabetes planned for expected uneventful cataract surgery were randomized to topical bromfenac (Yellox, n = 242), topical dexamethasone (n = 242), or a combination treatment (n = 238). All relevant resources from a healthcare perspective were included in the cost analysis within a time horizon of 12 weeks postoperatively. The main effectiveness outcome was quality-adjusted life years (QALYs). The main cost-effectiveness outcome was the incremental cost-effectiveness ratio (ICER) based on the cost per QALY. RESULTS: The study comprised 722 patients without diabetes. Total healthcare costs and QALYs were € 447 (US $562) and 0.174 in the bromfenac group, €421 (US $529) and 0.179 in the dexamethasone group, and €442 (US $565) and 0.182 in the combination group. Bromfenac was most costly and least effective (ie, strongly dominated). The ICER was €6544 (US $8221) per QALY for the combination group compared with the dexamethasone group. Assuming that the willingness to pay is € 20 000 (US $25 126) per QALY, the cost-effectiveness probability was 3%, 32%, and 65% in the bromfenac, dexamethasone, and combination groups, respectively. CONCLUSIONS: In patients without diabetes, combination treatment with topical bromfenac and dexamethasone was effective and cost-effective in preventing CME after cataract surgery compared with treatment with either drug alone.

Vascular risk factors for optical coherence tomography-detected macular cysts: The Maastricht Study.

PURPOSE: To investigate whether higher blood pressure and greater arterial stiffness are associated with the presence of macular cysts and whether this association is already present in the absence of micro-aneurysms in individuals with and without type 2 diabetes. METHODS: Using spectral domain optical coherence tomography (OCT), we performed a macular volume scan in 2647 individuals (mean age 60 ± 8 years, 50% men, 27% type 2 diabetes). The association between macular cysts and 24-hour systolic and diastolic blood pressure, pulse pressure, mean arterial blood pressure, carotid-femoral pulse wave velocity and carotid distensibility was assessed by use of logistic regression. RESULTS: Twenty-four hours systolic blood pressure was associated with the presence of macular cysts [OR = 1.03 (95% CI 1.00-1.05) per 1 mmHg, p = 0.03]. 24 hr pulse pressure [OR = 1.61 (95% CI 1.11-2.34) per 10 mmHg, p = 0.01] and carotid-femoral pulse wave velocity [OR = 1.16 (95% CI 1.02-1.32) per 1 m/s, p = 0.02] were associated with macular cysts, while carotid distensibility was not [OR = 1.03 (95% CI 0.96-1.11) per 1.0*10-3 /kPa, p = 0.45]. Associations were similar in individuals with and without type 2 diabetes and were already present in the absence of micro-aneurysms. CONCLUSION: Twenty-four hours systolic blood pressure, 24 hr pulse pressure and carotid-femoral pulse wave velocity are associated with the presence of OCT-detected macular cysts in individuals with and without type 2 diabetes, even in the absence of micro-aneurysms. Therefore, blood pressure and aortic stiffness are potential factors contributing to macular cysts.

Association of Retinal Nerve Fiber Layer Thickness, an Index of Neurodegeneration, With Depressive Symptoms Over Time.

Importance: Whether neurodegeneration contributes to the early pathobiology of late-life depression remains incompletely understood. Objective: To investigate whether lower retinal nerve fiber layer (RNFL) thickness, a marker of neurodegeneration, is associated with the incidence of clinically relevant depressive symptoms and depressive symptoms over time. Design, Setting, and Participants: This is a population-based cohort study from the Netherlands (The Maastricht Study) with baseline examination between 2010 and 2020 and median (IQR) follow-up of 5.0 (3.0-6.0) years. Participants were recruited from the general population. Individuals with type 2 diabetes were oversampled by design. Data analysis was performed from September 2020 to January 2021. Exposures: RNFL, an index of neurodegeneration, assessed with optical coherence tomography. Main Outcomes and Measures: Depressive symptoms were assessed with the Patient Health Questionnaire (PHQ)-9 (continuous score, 0-27) at baseline and over time via annual assessments. The presence of clinically relevant depressive symptoms was defined as a PHQ-9 score of 10 or higher. Results: We used data from 4934 participants with depressive symptoms over time (mean [SD] age, 59.7 [8.4] years; 2159 women [50.8%]; 870 had type 2 diabetes [20.5%]). Lower RNFL thickness was associated with higher incidence of clinically relevant depressive symptoms (per 1 SD, hazard ratio 1.11; 95% CI, 1.01-1.23) and more depressive symptoms over time (per 1 SD, rate ratio, 1.04; 95% CI, 1.01-1.06), after adjustment for demographic, cardiovascular, and lifestyle factors. Conclusions and Relevance: The findings of this study suggest that lower RNFL thickness is associated with higher incidence of clinically relevant depressive symptoms and more depressive symptoms over time. Hence, neurodegeneration may be associated with the early pathobiology of late-life depression.